Tara Haelle

AUSTIN, TEX. – Neuromuscular complications from immunotherapy for cancer are rare, but they occur often enough that it is helpful to know which ones can result from different immunotherapies and how to distinguish them from non–adverse event conditions, according to Christopher Trevino, MD, a neuro-oncologist at Tulane University in New Orleans.

At the annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine, Dr. Trevino reviewed immunotherapy types, particularly immune checkpoint inhibitors, and the most common neuromuscular complications – primarily neuropathy, myasthenia gravis (MG), myositis, and encephalitis or meningitis.

“Timing of onset is a critical component to assist in identifying immune checkpoint inhibitor–associated versus non–immune checkpoint inhibitor–associated neuromuscular disease,” Dr. Trevino told attendees. Prompt recognition can be particularly urgent for MG because crisis and death rates are higher when induced by immunotherapy and require quick treatment. “Understanding the mechanisms of action sets a foundation for treatment approach,” he added.

Any part of the nervous system can be affected by immunotherapy toxicity, he said, and syndromes often overlap, with the peripheral nervous system typically more often affected than the central nervous system. Neurologic immune-related adverse events typically occur within four cycles of therapy – about 12 weeks after therapy initiation – but should always involve a work-up to exclude effects from the cancer itself, other neuromuscular diagnoses unrelated to therapy, and other toxicities from chemotherapy.

Recommended first-line treatment is halting immunotherapy with or without corticosteroids, after which most patients improve, often with “rapid, complete resolution of symptoms,” Dr. Trevino said. Restarting immunotherapy treatment is possible in some patients, though.
 

CAR T-cell and dendritic cell vaccine therapies

Four main types of immunotherapy exist: viral therapy, vaccine therapy, immune checkpoint inhibitors, and adoptive cell transfer, such as chimeric antigen receptor (CAR) T-cell therapy. Dr. Trevino focused on checkpoint inhibitors and adoptive cell transfer.

CAR T-cell therapy is a multistep treatment process that involves first removing blood from the patient to obtain their T cells. These are used to create and grow CAR T cells in the lab so that they can be infused back into the patient. The cells then bind to cancer cells and destroy them. Examples of approved CAR T-cell therapy include Yescarta (axicabtagene ciloleucel) for some types of non-Hodgkin lymphoma and Kymriah (tisagenlecleucel) for acute lymphoblastic leukemia (ALL).

Dendritic cell vaccines are similar to CAR T-cell therapy in that they also use the patient’s own immune cells to create cancer-killing cells that the patient then receives back. The only currently approved dendritic cell vaccine is Provenge (sipuleucel-T) for advanced prostate cancer.

The main toxicity to watch for from CAR T-cell therapy and dendritic cell vaccines is cytokine release syndrome (CRS). It can begin anywhere from 1-14 days after the infusion and involves T-cell expansion in the body that leads to a cytokine storm. Symptoms are wide ranging, including fatigue, fever, loss of appetite, tachycardia, hypotension, pain, rash, diarrhea, headache, confusion, seizures, muscle and joint pain, tachypnea, hypoxia and hallucinations, among others.

Specific central neurotoxicities that can result from CAR T-cell therapy include encephalopathy, cerebral edema, seizures and status epilepticus, cerebral vasospasm, and aphasia.
 

Immune checkpoint inhibitor toxicities

Immune checkpoint inhibitors are drugs that interrupt a cancer’s ability to hijack the immune system; they block the proteins that hold back T-cells from attacking the cancer, thereby releasing the immune system to go after the malignant cells.

The two most common types of immune checkpoint inhibitors are those targeting the programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) pathways. The three currently approved PD-1 inhibitors are pembrolizumab (Keytruda), nivolumab (Opdivo), and cemiplimab (Libtayo), which can treat nearly a dozen malignancies affecting different organs. Atezolizumab (Tecentriq), avelumab (Bavencio), and durvalumab (Imfinzi) are the three currently approved PD-L1 inhibitors, indicated for urothelial carcinoma and a handful of other cancers, such as small-cell and non–small cell lung cancer and triple negative breast cancer.

The only other type of approved checkpoint inhibitor is ipilimumab (Yervoy), which targets the CTLA-4 protein. A number of other checkpoint inhibitors are in trials, however, such as ones targeting pathways involving OX40, ICOS, TIM3, and LAG-3 (J Hematol Oncol. 2018. doi: 10.1186/s13045-018-0582-8).

Immune-related adverse events are less common with PD-1 or PD-L1 inhibitors – a rate of 5%-10% – compared with adverse events from CTLA-4 inhibitors, which occur in about 15% of patients. Neurologic complications occur even more rarely – about 1%-4% of all immune checkpoint inhibitor therapies – and primarily include MG, Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), and inflammatory myositis (Muscle Nerve. 2018;58[1]:10-22).

Treatment with multiple checkpoint inhibitors increases the likelihood of severe adverse events, with rates of up to 30%-50% of patients with dual treatment.
 

Distinguishing features of neuromuscular immunotherapy-related adverse events

MG is the most common neuromuscular immune-related adverse event from immune checkpoint inhibitors and tends to occur 3-12 weeks after beginning treatment, frequently comorbid with inflammatory myopathy or cardiomyopathy, Dr. Trevino said. About two-thirds of cases are de novo, while the remaining one-third involve preexisting MG; no reports of Lambert-Eaton myasthenic syndrome have been linked to checkpoint inhibitors.

Several characteristics distinguish checkpoint inhibitor–associated MG from standard MG. Standard MG can be ocular with or without bulbar or appendicular weakness, whereas immunotherapy-related MG is rarely only ocular (about 18% of cases). Immunotherapy-related MG involves an MG crisis at diagnosis in up to 50% of cases and has high mortality, both of which are rarer with standard MG.

While standard MG can be seronegative or involve AChR, MuSK, or LRP4 antibodies, about two-thirds of immunotherapy-related MG cases are positive for AChR antibodies. LRP4 antibodies are rare with MG from checkpoint inhibitors, and no MuSK antibodies have been reported in these cases. Creatine kinase (CK) or troponin I (TnI) elevation occurs in about 87% of patients with checkpoint inhibitor-induced MG, but standard MG doesn’t typically involve increased CK levels.

Inflammatory myositis (IM), the second most common neuromuscular adverse event from immunotherapy, tends to occur 2-15 weeks after immune checkpoint inhibitor therapy and can involve polymyositis, necrotizing autoimmune myopathy, dermatomyositis, granulomatous myositis, or other nonspecific myositis and myopathies.

Though proximal weakness occurs with IM both associated with immunotherapy and not, ocular symptoms are unique to cases associated with therapy and occur in about half of them. Myalgia, dyspnea, and dysphagia can all occur with checkpoint inhibitor–associated IM but don’t generally occur with standard IM. Immunotherapy-related IM is usually seronegative for myositis antibodies and doesn’t generally cause abnormalities in electromyography, compared with increased exertional activity and early recruitment of myopathic motor units in electromyography with standard IM.

GBS and CIDP are the third most common cause of neuromuscular complications from checkpoint inhibitors. The main distinguishing feature of these conditions from those not related to immunotherapy is that they occur anywhere from 4 to 68 weeks after therapy begins. Presentation is otherwise similar whether related to checkpoint inhibitors or not.

Aside from GBS and CIDP, other neuropathies that can result from immunotherapy complications include acute cranial neuropathies, axonal or demyelinating neuropathies, motor polyradiculopathy, vasculitic neuropathy, and plexopathy.

Neuromuscular complications other than those described above can also occur from checkpoint inhibitor therapy, such as enteric neuropathy, polyradiculitis, and meningo-radiculo-neuritis, but these are much rarer.

Four organizations have developed consensus guidelines for immune checkpoint inhibitor toxicities: the European Society for Medical Oncology (ESMO, 2017), Society for Immunotherapy of Cancer (SITC, 2017), American Society of Clinical Oncology (ASCO, 2018), and National Comprehensive Cancer Network (NCCN, 2019).

Dr Trevino had no disclosures.

AUSTIN, TEX. – Neuromuscular complications from immunotherapy for cancer are rare, but they occur often enough that it is helpful to know which ones can result from different immunotherapies and how to distinguish them from non–adverse event conditions, according to Christopher Trevino, MD, a neuro-oncologist at Tulane University in New Orleans.

At the annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine, Dr. Trevino reviewed immunotherapy types, particularly immune checkpoint inhibitors, and the most common neuromuscular complications – primarily neuropathy, myasthenia gravis (MG), myositis, and encephalitis or meningitis.

“Timing of onset is a critical component to assist in identifying immune checkpoint inhibitor–associated versus non–immune checkpoint inhibitor–associated neuromuscular disease,” Dr. Trevino told attendees. Prompt recognition can be particularly urgent for MG because crisis and death rates are higher when induced by immunotherapy and require quick treatment. “Understanding the mechanisms of action sets a foundation for treatment approach,” he added.

Any part of the nervous system can be affected by immunotherapy toxicity, he said, and syndromes often overlap, with the peripheral nervous system typically more often affected than the central nervous system. Neurologic immune-related adverse events typically occur within four cycles of therapy – about 12 weeks after therapy initiation – but should always involve a work-up to exclude effects from the cancer itself, other neuromuscular diagnoses unrelated to therapy, and other toxicities from chemotherapy.

Recommended first-line treatment is halting immunotherapy with or without corticosteroids, after which most patients improve, often with “rapid, complete resolution of symptoms,” Dr. Trevino said. Restarting immunotherapy treatment is possible in some patients, though.
 

CAR T-cell and dendritic cell vaccine therapies

Four main types of immunotherapy exist: viral therapy, vaccine therapy, immune checkpoint inhibitors, and adoptive cell transfer, such as chimeric antigen receptor (CAR) T-cell therapy. Dr. Trevino focused on checkpoint inhibitors and adoptive cell transfer.

CAR T-cell therapy is a multistep treatment process that involves first removing blood from the patient to obtain their T cells. These are used to create and grow CAR T cells in the lab so that they can be infused back into the patient. The cells then bind to cancer cells and destroy them. Examples of approved CAR T-cell therapy include Yescarta (axicabtagene ciloleucel) for some types of non-Hodgkin lymphoma and Kymriah (tisagenlecleucel) for acute lymphoblastic leukemia (ALL).

Dendritic cell vaccines are similar to CAR T-cell therapy in that they also use the patient’s own immune cells to create cancer-killing cells that the patient then receives back. The only currently approved dendritic cell vaccine is Provenge (sipuleucel-T) for advanced prostate cancer.

The main toxicity to watch for from CAR T-cell therapy and dendritic cell vaccines is cytokine release syndrome (CRS). It can begin anywhere from 1-14 days after the infusion and involves T-cell expansion in the body that leads to a cytokine storm. Symptoms are wide ranging, including fatigue, fever, loss of appetite, tachycardia, hypotension, pain, rash, diarrhea, headache, confusion, seizures, muscle and joint pain, tachypnea, hypoxia and hallucinations, among others.

Specific central neurotoxicities that can result from CAR T-cell therapy include encephalopathy, cerebral edema, seizures and status epilepticus, cerebral vasospasm, and aphasia.
 

Immune checkpoint inhibitor toxicities

Immune checkpoint inhibitors are drugs that interrupt a cancer’s ability to hijack the immune system; they block the proteins that hold back T-cells from attacking the cancer, thereby releasing the immune system to go after the malignant cells.

The two most common types of immune checkpoint inhibitors are those targeting the programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) pathways. The three currently approved PD-1 inhibitors are pembrolizumab (Keytruda), nivolumab (Opdivo), and cemiplimab (Libtayo), which can treat nearly a dozen malignancies affecting different organs. Atezolizumab (Tecentriq), avelumab (Bavencio), and durvalumab (Imfinzi) are the three currently approved PD-L1 inhibitors, indicated for urothelial carcinoma and a handful of other cancers, such as small-cell and non–small cell lung cancer and triple negative breast cancer.

The only other type of approved checkpoint inhibitor is ipilimumab (Yervoy), which targets the CTLA-4 protein. A number of other checkpoint inhibitors are in trials, however, such as ones targeting pathways involving OX40, ICOS, TIM3, and LAG-3 (J Hematol Oncol. 2018. doi: 10.1186/s13045-018-0582-8).

Immune-related adverse events are less common with PD-1 or PD-L1 inhibitors – a rate of 5%-10% – compared with adverse events from CTLA-4 inhibitors, which occur in about 15% of patients. Neurologic complications occur even more rarely – about 1%-4% of all immune checkpoint inhibitor therapies – and primarily include MG, Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), and inflammatory myositis (Muscle Nerve. 2018;58[1]:10-22).

Treatment with multiple checkpoint inhibitors increases the likelihood of severe adverse events, with rates of up to 30%-50% of patients with dual treatment.
 

Distinguishing features of neuromuscular immunotherapy-related adverse events

MG is the most common neuromuscular immune-related adverse event from immune checkpoint inhibitors and tends to occur 3-12 weeks after beginning treatment, frequently comorbid with inflammatory myopathy or cardiomyopathy, Dr. Trevino said. About two-thirds of cases are de novo, while the remaining one-third involve preexisting MG; no reports of Lambert-Eaton myasthenic syndrome have been linked to checkpoint inhibitors.

Several characteristics distinguish checkpoint inhibitor–associated MG from standard MG. Standard MG can be ocular with or without bulbar or appendicular weakness, whereas immunotherapy-related MG is rarely only ocular (about 18% of cases). Immunotherapy-related MG involves an MG crisis at diagnosis in up to 50% of cases and has high mortality, both of which are rarer with standard MG.

While standard MG can be seronegative or involve AChR, MuSK, or LRP4 antibodies, about two-thirds of immunotherapy-related MG cases are positive for AChR antibodies. LRP4 antibodies are rare with MG from checkpoint inhibitors, and no MuSK antibodies have been reported in these cases. Creatine kinase (CK) or troponin I (TnI) elevation occurs in about 87% of patients with checkpoint inhibitor-induced MG, but standard MG doesn’t typically involve increased CK levels.

Inflammatory myositis (IM), the second most common neuromuscular adverse event from immunotherapy, tends to occur 2-15 weeks after immune checkpoint inhibitor therapy and can involve polymyositis, necrotizing autoimmune myopathy, dermatomyositis, granulomatous myositis, or other nonspecific myositis and myopathies.

Though proximal weakness occurs with IM both associated with immunotherapy and not, ocular symptoms are unique to cases associated with therapy and occur in about half of them. Myalgia, dyspnea, and dysphagia can all occur with checkpoint inhibitor–associated IM but don’t generally occur with standard IM. Immunotherapy-related IM is usually seronegative for myositis antibodies and doesn’t generally cause abnormalities in electromyography, compared with increased exertional activity and early recruitment of myopathic motor units in electromyography with standard IM.

GBS and CIDP are the third most common cause of neuromuscular complications from checkpoint inhibitors. The main distinguishing feature of these conditions from those not related to immunotherapy is that they occur anywhere from 4 to 68 weeks after therapy begins. Presentation is otherwise similar whether related to checkpoint inhibitors or not.

Aside from GBS and CIDP, other neuropathies that can result from immunotherapy complications include acute cranial neuropathies, axonal or demyelinating neuropathies, motor polyradiculopathy, vasculitic neuropathy, and plexopathy.

Neuromuscular complications other than those described above can also occur from checkpoint inhibitor therapy, such as enteric neuropathy, polyradiculitis, and meningo-radiculo-neuritis, but these are much rarer.

Four organizations have developed consensus guidelines for immune checkpoint inhibitor toxicities: the European Society for Medical Oncology (ESMO, 2017), Society for Immunotherapy of Cancer (SITC, 2017), American Society of Clinical Oncology (ASCO, 2018), and National Comprehensive Cancer Network (NCCN, 2019).

Dr Trevino had no disclosures.

AUSTIN, TEX. – Neuromuscular complications from immunotherapy for cancer are rare, but they occur often enough that it is helpful to know which ones can result from different immunotherapies and how to distinguish them from non–adverse event conditions, according to Christopher Trevino, MD, a neuro-oncologist at Tulane University in New Orleans.

At the annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine, Dr. Trevino reviewed immunotherapy types, particularly immune checkpoint inhibitors, and the most common neuromuscular complications – primarily neuropathy, myasthenia gravis (MG), myositis, and encephalitis or meningitis.

“Timing of onset is a critical component to assist in identifying immune checkpoint inhibitor–associated versus non–immune checkpoint inhibitor–associated neuromuscular disease,” Dr. Trevino told attendees. Prompt recognition can be particularly urgent for MG because crisis and death rates are higher when induced by immunotherapy and require quick treatment. “Understanding the mechanisms of action sets a foundation for treatment approach,” he added.

Any part of the nervous system can be affected by immunotherapy toxicity, he said, and syndromes often overlap, with the peripheral nervous system typically more often affected than the central nervous system. Neurologic immune-related adverse events typically occur within four cycles of therapy – about 12 weeks after therapy initiation – but should always involve a work-up to exclude effects from the cancer itself, other neuromuscular diagnoses unrelated to therapy, and other toxicities from chemotherapy.

Recommended first-line treatment is halting immunotherapy with or without corticosteroids, after which most patients improve, often with “rapid, complete resolution of symptoms,” Dr. Trevino said. Restarting immunotherapy treatment is possible in some patients, though.
 

CAR T-cell and dendritic cell vaccine therapies

Four main types of immunotherapy exist: viral therapy, vaccine therapy, immune checkpoint inhibitors, and adoptive cell transfer, such as chimeric antigen receptor (CAR) T-cell therapy. Dr. Trevino focused on checkpoint inhibitors and adoptive cell transfer.

CAR T-cell therapy is a multistep treatment process that involves first removing blood from the patient to obtain their T cells. These are used to create and grow CAR T cells in the lab so that they can be infused back into the patient. The cells then bind to cancer cells and destroy them. Examples of approved CAR T-cell therapy include Yescarta (axicabtagene ciloleucel) for some types of non-Hodgkin lymphoma and Kymriah (tisagenlecleucel) for acute lymphoblastic leukemia (ALL).

Dendritic cell vaccines are similar to CAR T-cell therapy in that they also use the patient’s own immune cells to create cancer-killing cells that the patient then receives back. The only currently approved dendritic cell vaccine is Provenge (sipuleucel-T) for advanced prostate cancer.

The main toxicity to watch for from CAR T-cell therapy and dendritic cell vaccines is cytokine release syndrome (CRS). It can begin anywhere from 1-14 days after the infusion and involves T-cell expansion in the body that leads to a cytokine storm. Symptoms are wide ranging, including fatigue, fever, loss of appetite, tachycardia, hypotension, pain, rash, diarrhea, headache, confusion, seizures, muscle and joint pain, tachypnea, hypoxia and hallucinations, among others.

Specific central neurotoxicities that can result from CAR T-cell therapy include encephalopathy, cerebral edema, seizures and status epilepticus, cerebral vasospasm, and aphasia.
 

Immune checkpoint inhibitor toxicities

Immune checkpoint inhibitors are drugs that interrupt a cancer’s ability to hijack the immune system; they block the proteins that hold back T-cells from attacking the cancer, thereby releasing the immune system to go after the malignant cells.

The two most common types of immune checkpoint inhibitors are those targeting the programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) pathways. The three currently approved PD-1 inhibitors are pembrolizumab (Keytruda), nivolumab (Opdivo), and cemiplimab (Libtayo), which can treat nearly a dozen malignancies affecting different organs. Atezolizumab (Tecentriq), avelumab (Bavencio), and durvalumab (Imfinzi) are the three currently approved PD-L1 inhibitors, indicated for urothelial carcinoma and a handful of other cancers, such as small-cell and non–small cell lung cancer and triple negative breast cancer.

The only other type of approved checkpoint inhibitor is ipilimumab (Yervoy), which targets the CTLA-4 protein. A number of other checkpoint inhibitors are in trials, however, such as ones targeting pathways involving OX40, ICOS, TIM3, and LAG-3 (J Hematol Oncol. 2018. doi: 10.1186/s13045-018-0582-8).

Immune-related adverse events are less common with PD-1 or PD-L1 inhibitors – a rate of 5%-10% – compared with adverse events from CTLA-4 inhibitors, which occur in about 15% of patients. Neurologic complications occur even more rarely – about 1%-4% of all immune checkpoint inhibitor therapies – and primarily include MG, Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), and inflammatory myositis (Muscle Nerve. 2018;58[1]:10-22).

Treatment with multiple checkpoint inhibitors increases the likelihood of severe adverse events, with rates of up to 30%-50% of patients with dual treatment.
 

Distinguishing features of neuromuscular immunotherapy-related adverse events

MG is the most common neuromuscular immune-related adverse event from immune checkpoint inhibitors and tends to occur 3-12 weeks after beginning treatment, frequently comorbid with inflammatory myopathy or cardiomyopathy, Dr. Trevino said. About two-thirds of cases are de novo, while the remaining one-third involve preexisting MG; no reports of Lambert-Eaton myasthenic syndrome have been linked to checkpoint inhibitors.

Several characteristics distinguish checkpoint inhibitor–associated MG from standard MG. Standard MG can be ocular with or without bulbar or appendicular weakness, whereas immunotherapy-related MG is rarely only ocular (about 18% of cases). Immunotherapy-related MG involves an MG crisis at diagnosis in up to 50% of cases and has high mortality, both of which are rarer with standard MG.

While standard MG can be seronegative or involve AChR, MuSK, or LRP4 antibodies, about two-thirds of immunotherapy-related MG cases are positive for AChR antibodies. LRP4 antibodies are rare with MG from checkpoint inhibitors, and no MuSK antibodies have been reported in these cases. Creatine kinase (CK) or troponin I (TnI) elevation occurs in about 87% of patients with checkpoint inhibitor-induced MG, but standard MG doesn’t typically involve increased CK levels.

Inflammatory myositis (IM), the second most common neuromuscular adverse event from immunotherapy, tends to occur 2-15 weeks after immune checkpoint inhibitor therapy and can involve polymyositis, necrotizing autoimmune myopathy, dermatomyositis, granulomatous myositis, or other nonspecific myositis and myopathies.

Though proximal weakness occurs with IM both associated with immunotherapy and not, ocular symptoms are unique to cases associated with therapy and occur in about half of them. Myalgia, dyspnea, and dysphagia can all occur with checkpoint inhibitor–associated IM but don’t generally occur with standard IM. Immunotherapy-related IM is usually seronegative for myositis antibodies and doesn’t generally cause abnormalities in electromyography, compared with increased exertional activity and early recruitment of myopathic motor units in electromyography with standard IM.

GBS and CIDP are the third most common cause of neuromuscular complications from checkpoint inhibitors. The main distinguishing feature of these conditions from those not related to immunotherapy is that they occur anywhere from 4 to 68 weeks after therapy begins. Presentation is otherwise similar whether related to checkpoint inhibitors or not.

Aside from GBS and CIDP, other neuropathies that can result from immunotherapy complications include acute cranial neuropathies, axonal or demyelinating neuropathies, motor polyradiculopathy, vasculitic neuropathy, and plexopathy.

Neuromuscular complications other than those described above can also occur from checkpoint inhibitor therapy, such as enteric neuropathy, polyradiculitis, and meningo-radiculo-neuritis, but these are much rarer.

Four organizations have developed consensus guidelines for immune checkpoint inhibitor toxicities: the European Society for Medical Oncology (ESMO, 2017), Society for Immunotherapy of Cancer (SITC, 2017), American Society of Clinical Oncology (ASCO, 2018), and National Comprehensive Cancer Network (NCCN, 2019).

Dr Trevino had no disclosures.

NEW ORLEANS – Social media and electronics aren’t the only barriers to a good night’s sleep for teens, according to Adiaha I. A. Spinks-Franklin, MD, MPH, a pediatrician at Texas Children’s Hospital in Houston.

junpinzon/Thinkstock

Another half-dozen “sleep enemies” interfere with adolescents’ sleep and can contribute to insomnia or other sleep disorders, she told attendees at the annual meeting of the American Academy of Pediatrics.

Knowing what normal sleep physiology looks like in youth and understanding the most common sleep enemies and sleep-behavior problems can help you use effective interventions to help your patients get the sleep they need, she said.

Infants need the most sleep, about 12-16 hours each 24-hour period, including naps, for those aged 4-12 months. As they grow into toddlerhood and preschool age, children gradually need less: Children aged 1-2 years need 11-14 hours and children aged 3-5 years need 10-13 hours, including naps. By the time children are in school, ages 6-12, they should have dropped their naps and need 9-12 hours a night.

Parents may expect teens can get by with only as much sleep as adults need, but teens actually need 8-10 hours of sleep a night, and many don’t get that much. In fact, 75% of high school seniors get less than 8 hours of sleep a day and live with a chronic sleep debt, Dr. Spinks-Franklin said.

Although social media use and electronics in the bedroom – TVs, computers, cell phones, and video games – can certainly contribute to inadequate sleep, a heavy academic load and extracurricular activities can be just as problematic, Dr. Spinks-Franklin said. Teens who work after school also may have difficulty getting enough sleep, especially if they also have to balance a heavier academic load or even one or two extracurricular activities.

Socializing with friends also can interfere with sleep, especially when get-togethers run late; drinking caffeinated drinks in the afternoon onward can make it difficult for adolescents to get the sleep they need as well. Less-modifiable contributors to too little sleep are stress and early school start times, Dr. Spinks-Franklin said.

The two most common sleep problems seen in teens are insomnia and delayed sleep phase syndrome. Addressing these is important because the effects of chronic insufficient sleep can have far-reaching consequences. Obesity and related chronic health conditions are associated with inadequate sleep, as are poor academic performance, poor judgment, poor executive functioning, and mental health disorders like depression.

Short-term effects of insufficient sleep also can be problematic and can exacerbate existing sleep problems, such as sleeping in on the weekends to “catch up” on sleep or drinking more caffeine to try to stay awake during the day. Increased caffeine intake can interfere with non-REM deep sleep, Dr. Spinks-Franklin said, and therefore reduce the quality of sleep even if the person gets the total hours they need.

Insomnia in adolescents

Insomnia can refer to difficulty falling asleep, staying asleep, sleeping for long enough, or getting enough sleep in one period of time even when the opportunity is there. Some people may have no trouble falling asleep, but they wake up too early – before they have had gotten the sleep they need – and cannot return to sleep.

To be insomnia, the problem must occur “despite having enough time available for sleep,” Dr. Spinks-Franklin said. “Patient who restrict the amount of time for sleep due to work or social commitments may have trouble sleeping and daytime sleepiness but do not have insomnia.”

Daytime impairment also is part of the American Academy of Sleep Medicine’s definition of insomnia. The rare teen who doesn’t need as much sleep as average and functions without difficulty during the day does not necessarily have insomnia.

But the impairment may not necessarily just be fatigue or sleepiness. In fact, many of the symptoms are the same as those seen with ADHD.

Daytime consequences of insomnia can include the following:

• Depression, feeling sad or “blue,” or emotional hypersensitivity.
• Mood swings, crankiness, or irritability.
• Difficulty concentrating or paying attention, poor memory, mind wandering, or even inability to sit still.
• Job or school problems, such as not being able to finish homework, not finishing tasks they start, or forgetfulness.
• Difficulty in social situations, such as discomfort with others or problems with friends.
• Daytime sleepiness, even when unable to actually take a nap.
• Behavioral problems, such as hyperactivity, impulsivity, or aggression.
• Frequent mistakes, especially at work, at school, or while driving (often “errors of omission,” such as not seeing a street sign or not hearing an instruction).
• Lower levels of motivation or initiative, feeling less energetic.
• Excessive worry about sleep.

Evaluation of insomnia can be framed with “the three-factor model,” which includes predisposing factors, precipitating factors, and perpetuating factors.

Predisposing factors – those that indicate a person already may be at risk for insomnia – include potential genetic influences as well as their typical response to stress. “Do they sleep more or less?” Dr. Spinks-Franklin said. Even teens predisposed to insomnia may not develop it, however, without a precipitating trigger.

These triggers could include stress, anxiety, poor initial sleep hygiene that becomes a pattern, dietary intake or behaviors (such as drinking caffeine or eating too much or too late in the evening), changes to their schedule, or side effects of medications.

Once insomnia begins, various factors can then perpetuate the cycle, including some of those that triggered it, such as anxiety or a school or work schedule. Sometimes it can be difficult to pinpoint the factor prolonging insomnia, such as the unconscious reward of going to work or school late with few or no consequences.

Delayed sleep phase syndrome

Delayed sleep phase syndrome occurs when someone has a delayed onset of melatonin secretion that pushes back the time when they can fall asleep. Melatonin is the neurotransmitter produced by the pineal gland that signals the start of nighttime. Although it has a hereditary component, delayed sleep phase syndrome also can result from a pattern of poor sleep onset and sleeping in on the weekends.

Dr. Spinks-Franklin described the typical cycle: A teen doesn’t go to sleep until after midnight and then wants to sleep in later in the morning. Because they have to wake up early for school, they sleep in on the weekends to try to regain the sleep they lost. Sleeping in pushes their circadian rhythm even later, perpetuating the problem.

Interventions for sleep disorders

The recommended treatment for insomnia is cognitive-behavior therapy for insomnia, for which strong evidence exists. Before seeking cognitive-behavior therapy, however, families can work to improve sleep hygiene and reduce stimuli that contribute to insomnia.

Teens should avoid screens for at least 1 hour before bedtime and avoid caffeine and exercise for at least 4 hours before going to bed. They also need to develop a schedule with a consistent bedtime and wake-up time, including on the weekends. They should avoid sleeping in on the weekends or taking naps during the day, Dr. Spinks-Franklin said.

Delayed sleep phase syndrome is more resistant to treatment and has a high recurrence rate, she said, and it requires commitment from the parent and their child to address it successfully. Teens with this condition also can start with sleep hygiene practices: a consistent wake-up time that they maintain on the weekends and no daytime naps. Phototherapy in the morning can be added to hopefully induce an earlier onset of melatonin release in the evening.

The next step is making changes to the youth’s schedule, particularly evening and/or weekend activities. They can try to gradually advance their biological clock by changing their sleep schedule.

Dr. Spinks-Franklin also briefly addressed the use of over-the-counter melatonin supplements for treating sleep problems. Melatonin can be effective for treating insomnia by improving sleep onset and sleep quality, particularly in children and teens with autism spectrum disorder or ADHD.

Dr. Spinks-Franklin had no disclosures, and her presentation used no outside funding.

NEW ORLEANS – Social media and electronics aren’t the only barriers to a good night’s sleep for teens, according to Adiaha I. A. Spinks-Franklin, MD, MPH, a pediatrician at Texas Children’s Hospital in Houston.

junpinzon/Thinkstock

Another half-dozen “sleep enemies” interfere with adolescents’ sleep and can contribute to insomnia or other sleep disorders, she told attendees at the annual meeting of the American Academy of Pediatrics.

Knowing what normal sleep physiology looks like in youth and understanding the most common sleep enemies and sleep-behavior problems can help you use effective interventions to help your patients get the sleep they need, she said.

Infants need the most sleep, about 12-16 hours each 24-hour period, including naps, for those aged 4-12 months. As they grow into toddlerhood and preschool age, children gradually need less: Children aged 1-2 years need 11-14 hours and children aged 3-5 years need 10-13 hours, including naps. By the time children are in school, ages 6-12, they should have dropped their naps and need 9-12 hours a night.

Parents may expect teens can get by with only as much sleep as adults need, but teens actually need 8-10 hours of sleep a night, and many don’t get that much. In fact, 75% of high school seniors get less than 8 hours of sleep a day and live with a chronic sleep debt, Dr. Spinks-Franklin said.

Although social media use and electronics in the bedroom – TVs, computers, cell phones, and video games – can certainly contribute to inadequate sleep, a heavy academic load and extracurricular activities can be just as problematic, Dr. Spinks-Franklin said. Teens who work after school also may have difficulty getting enough sleep, especially if they also have to balance a heavier academic load or even one or two extracurricular activities.

Socializing with friends also can interfere with sleep, especially when get-togethers run late; drinking caffeinated drinks in the afternoon onward can make it difficult for adolescents to get the sleep they need as well. Less-modifiable contributors to too little sleep are stress and early school start times, Dr. Spinks-Franklin said.

The two most common sleep problems seen in teens are insomnia and delayed sleep phase syndrome. Addressing these is important because the effects of chronic insufficient sleep can have far-reaching consequences. Obesity and related chronic health conditions are associated with inadequate sleep, as are poor academic performance, poor judgment, poor executive functioning, and mental health disorders like depression.

Short-term effects of insufficient sleep also can be problematic and can exacerbate existing sleep problems, such as sleeping in on the weekends to “catch up” on sleep or drinking more caffeine to try to stay awake during the day. Increased caffeine intake can interfere with non-REM deep sleep, Dr. Spinks-Franklin said, and therefore reduce the quality of sleep even if the person gets the total hours they need.

Insomnia in adolescents

Insomnia can refer to difficulty falling asleep, staying asleep, sleeping for long enough, or getting enough sleep in one period of time even when the opportunity is there. Some people may have no trouble falling asleep, but they wake up too early – before they have had gotten the sleep they need – and cannot return to sleep.

To be insomnia, the problem must occur “despite having enough time available for sleep,” Dr. Spinks-Franklin said. “Patient who restrict the amount of time for sleep due to work or social commitments may have trouble sleeping and daytime sleepiness but do not have insomnia.”

Daytime impairment also is part of the American Academy of Sleep Medicine’s definition of insomnia. The rare teen who doesn’t need as much sleep as average and functions without difficulty during the day does not necessarily have insomnia.

But the impairment may not necessarily just be fatigue or sleepiness. In fact, many of the symptoms are the same as those seen with ADHD.

Daytime consequences of insomnia can include the following:

• Depression, feeling sad or “blue,” or emotional hypersensitivity.
• Mood swings, crankiness, or irritability.
• Difficulty concentrating or paying attention, poor memory, mind wandering, or even inability to sit still.
• Job or school problems, such as not being able to finish homework, not finishing tasks they start, or forgetfulness.
• Difficulty in social situations, such as discomfort with others or problems with friends.
• Daytime sleepiness, even when unable to actually take a nap.
• Behavioral problems, such as hyperactivity, impulsivity, or aggression.
• Frequent mistakes, especially at work, at school, or while driving (often “errors of omission,” such as not seeing a street sign or not hearing an instruction).
• Lower levels of motivation or initiative, feeling less energetic.
• Excessive worry about sleep.

Evaluation of insomnia can be framed with “the three-factor model,” which includes predisposing factors, precipitating factors, and perpetuating factors.

Predisposing factors – those that indicate a person already may be at risk for insomnia – include potential genetic influences as well as their typical response to stress. “Do they sleep more or less?” Dr. Spinks-Franklin said. Even teens predisposed to insomnia may not develop it, however, without a precipitating trigger.

These triggers could include stress, anxiety, poor initial sleep hygiene that becomes a pattern, dietary intake or behaviors (such as drinking caffeine or eating too much or too late in the evening), changes to their schedule, or side effects of medications.

Once insomnia begins, various factors can then perpetuate the cycle, including some of those that triggered it, such as anxiety or a school or work schedule. Sometimes it can be difficult to pinpoint the factor prolonging insomnia, such as the unconscious reward of going to work or school late with few or no consequences.

Delayed sleep phase syndrome

Delayed sleep phase syndrome occurs when someone has a delayed onset of melatonin secretion that pushes back the time when they can fall asleep. Melatonin is the neurotransmitter produced by the pineal gland that signals the start of nighttime. Although it has a hereditary component, delayed sleep phase syndrome also can result from a pattern of poor sleep onset and sleeping in on the weekends.

Dr. Spinks-Franklin described the typical cycle: A teen doesn’t go to sleep until after midnight and then wants to sleep in later in the morning. Because they have to wake up early for school, they sleep in on the weekends to try to regain the sleep they lost. Sleeping in pushes their circadian rhythm even later, perpetuating the problem.

Interventions for sleep disorders

The recommended treatment for insomnia is cognitive-behavior therapy for insomnia, for which strong evidence exists. Before seeking cognitive-behavior therapy, however, families can work to improve sleep hygiene and reduce stimuli that contribute to insomnia.

Teens should avoid screens for at least 1 hour before bedtime and avoid caffeine and exercise for at least 4 hours before going to bed. They also need to develop a schedule with a consistent bedtime and wake-up time, including on the weekends. They should avoid sleeping in on the weekends or taking naps during the day, Dr. Spinks-Franklin said.

Delayed sleep phase syndrome is more resistant to treatment and has a high recurrence rate, she said, and it requires commitment from the parent and their child to address it successfully. Teens with this condition also can start with sleep hygiene practices: a consistent wake-up time that they maintain on the weekends and no daytime naps. Phototherapy in the morning can be added to hopefully induce an earlier onset of melatonin release in the evening.

The next step is making changes to the youth’s schedule, particularly evening and/or weekend activities. They can try to gradually advance their biological clock by changing their sleep schedule.

Dr. Spinks-Franklin also briefly addressed the use of over-the-counter melatonin supplements for treating sleep problems. Melatonin can be effective for treating insomnia by improving sleep onset and sleep quality, particularly in children and teens with autism spectrum disorder or ADHD.

Dr. Spinks-Franklin had no disclosures, and her presentation used no outside funding.

NEW ORLEANS – Social media and electronics aren’t the only barriers to a good night’s sleep for teens, according to Adiaha I. A. Spinks-Franklin, MD, MPH, a pediatrician at Texas Children’s Hospital in Houston.

junpinzon/Thinkstock

Another half-dozen “sleep enemies” interfere with adolescents’ sleep and can contribute to insomnia or other sleep disorders, she told attendees at the annual meeting of the American Academy of Pediatrics.

Knowing what normal sleep physiology looks like in youth and understanding the most common sleep enemies and sleep-behavior problems can help you use effective interventions to help your patients get the sleep they need, she said.

Infants need the most sleep, about 12-16 hours each 24-hour period, including naps, for those aged 4-12 months. As they grow into toddlerhood and preschool age, children gradually need less: Children aged 1-2 years need 11-14 hours and children aged 3-5 years need 10-13 hours, including naps. By the time children are in school, ages 6-12, they should have dropped their naps and need 9-12 hours a night.

Parents may expect teens can get by with only as much sleep as adults need, but teens actually need 8-10 hours of sleep a night, and many don’t get that much. In fact, 75% of high school seniors get less than 8 hours of sleep a day and live with a chronic sleep debt, Dr. Spinks-Franklin said.

Although social media use and electronics in the bedroom – TVs, computers, cell phones, and video games – can certainly contribute to inadequate sleep, a heavy academic load and extracurricular activities can be just as problematic, Dr. Spinks-Franklin said. Teens who work after school also may have difficulty getting enough sleep, especially if they also have to balance a heavier academic load or even one or two extracurricular activities.

Socializing with friends also can interfere with sleep, especially when get-togethers run late; drinking caffeinated drinks in the afternoon onward can make it difficult for adolescents to get the sleep they need as well. Less-modifiable contributors to too little sleep are stress and early school start times, Dr. Spinks-Franklin said.

The two most common sleep problems seen in teens are insomnia and delayed sleep phase syndrome. Addressing these is important because the effects of chronic insufficient sleep can have far-reaching consequences. Obesity and related chronic health conditions are associated with inadequate sleep, as are poor academic performance, poor judgment, poor executive functioning, and mental health disorders like depression.

Short-term effects of insufficient sleep also can be problematic and can exacerbate existing sleep problems, such as sleeping in on the weekends to “catch up” on sleep or drinking more caffeine to try to stay awake during the day. Increased caffeine intake can interfere with non-REM deep sleep, Dr. Spinks-Franklin said, and therefore reduce the quality of sleep even if the person gets the total hours they need.

Insomnia in adolescents

Insomnia can refer to difficulty falling asleep, staying asleep, sleeping for long enough, or getting enough sleep in one period of time even when the opportunity is there. Some people may have no trouble falling asleep, but they wake up too early – before they have had gotten the sleep they need – and cannot return to sleep.

To be insomnia, the problem must occur “despite having enough time available for sleep,” Dr. Spinks-Franklin said. “Patient who restrict the amount of time for sleep due to work or social commitments may have trouble sleeping and daytime sleepiness but do not have insomnia.”

Daytime impairment also is part of the American Academy of Sleep Medicine’s definition of insomnia. The rare teen who doesn’t need as much sleep as average and functions without difficulty during the day does not necessarily have insomnia.

But the impairment may not necessarily just be fatigue or sleepiness. In fact, many of the symptoms are the same as those seen with ADHD.

Daytime consequences of insomnia can include the following:

• Depression, feeling sad or “blue,” or emotional hypersensitivity.
• Mood swings, crankiness, or irritability.
• Difficulty concentrating or paying attention, poor memory, mind wandering, or even inability to sit still.
• Job or school problems, such as not being able to finish homework, not finishing tasks they start, or forgetfulness.
• Difficulty in social situations, such as discomfort with others or problems with friends.
• Daytime sleepiness, even when unable to actually take a nap.
• Behavioral problems, such as hyperactivity, impulsivity, or aggression.
• Frequent mistakes, especially at work, at school, or while driving (often “errors of omission,” such as not seeing a street sign or not hearing an instruction).
• Lower levels of motivation or initiative, feeling less energetic.
• Excessive worry about sleep.

Evaluation of insomnia can be framed with “the three-factor model,” which includes predisposing factors, precipitating factors, and perpetuating factors.

Predisposing factors – those that indicate a person already may be at risk for insomnia – include potential genetic influences as well as their typical response to stress. “Do they sleep more or less?” Dr. Spinks-Franklin said. Even teens predisposed to insomnia may not develop it, however, without a precipitating trigger.

These triggers could include stress, anxiety, poor initial sleep hygiene that becomes a pattern, dietary intake or behaviors (such as drinking caffeine or eating too much or too late in the evening), changes to their schedule, or side effects of medications.

Once insomnia begins, various factors can then perpetuate the cycle, including some of those that triggered it, such as anxiety or a school or work schedule. Sometimes it can be difficult to pinpoint the factor prolonging insomnia, such as the unconscious reward of going to work or school late with few or no consequences.

Delayed sleep phase syndrome

Delayed sleep phase syndrome occurs when someone has a delayed onset of melatonin secretion that pushes back the time when they can fall asleep. Melatonin is the neurotransmitter produced by the pineal gland that signals the start of nighttime. Although it has a hereditary component, delayed sleep phase syndrome also can result from a pattern of poor sleep onset and sleeping in on the weekends.

Dr. Spinks-Franklin described the typical cycle: A teen doesn’t go to sleep until after midnight and then wants to sleep in later in the morning. Because they have to wake up early for school, they sleep in on the weekends to try to regain the sleep they lost. Sleeping in pushes their circadian rhythm even later, perpetuating the problem.

Interventions for sleep disorders

The recommended treatment for insomnia is cognitive-behavior therapy for insomnia, for which strong evidence exists. Before seeking cognitive-behavior therapy, however, families can work to improve sleep hygiene and reduce stimuli that contribute to insomnia.

Teens should avoid screens for at least 1 hour before bedtime and avoid caffeine and exercise for at least 4 hours before going to bed. They also need to develop a schedule with a consistent bedtime and wake-up time, including on the weekends. They should avoid sleeping in on the weekends or taking naps during the day, Dr. Spinks-Franklin said.

Delayed sleep phase syndrome is more resistant to treatment and has a high recurrence rate, she said, and it requires commitment from the parent and their child to address it successfully. Teens with this condition also can start with sleep hygiene practices: a consistent wake-up time that they maintain on the weekends and no daytime naps. Phototherapy in the morning can be added to hopefully induce an earlier onset of melatonin release in the evening.

The next step is making changes to the youth’s schedule, particularly evening and/or weekend activities. They can try to gradually advance their biological clock by changing their sleep schedule.

Dr. Spinks-Franklin also briefly addressed the use of over-the-counter melatonin supplements for treating sleep problems. Melatonin can be effective for treating insomnia by improving sleep onset and sleep quality, particularly in children and teens with autism spectrum disorder or ADHD.

Dr. Spinks-Franklin had no disclosures, and her presentation used no outside funding.

AUSTIN, TEX. – Real-world effectiveness of ataluren for the treatment of Duchenne muscular dystrophy (DMD) with nonsense mutation was similar to the benefit seen in the randomized controlled trial that led to its European approval, according to new data.

“Participants in the STRIDE Registry [real-world patients] showed a reduction in functional decline over 48 weeks, compared with patients receiving placebo” in the trial, reported Abdallah Delage of PTC Therapeutics in Zug, Switzerland, and his associates.

Duchenne muscular dystrophy affects an estimated 1 in 3,600-6,000 male births globally, about 10%-15% of whom have nonsense mutation DMD. This mutation causes a truncated, nonfunctional dystrophin protein due to a premature stop codon, the authors explained. Ataluren “promotes ribosomal read-through of the premature stop codon to produce a full-length dystrophin protein,” they explained.

Ataluren is currently approved for ambulatory patients age 2 and older with nonsense mutation DMD in the European Union and several other European countries. Israel, Korea, Chile, and Ukraine have approved it for patients aged 5 and older.

The Strategic Targeting of Registries and International Database of Excellence (STRIDE) Registry contains real-world data from patients using ataluren as part of an ongoing multicenter observational postapproval safety study. The investigators are tracking patients for at least 5 years after enrollment in 14 countries where ataluren is approved or commercially available through early-access programs. Patients take 40 mg/kg daily: 10 mg/kg in the morning, 10 mg/kg midday, and 20 mg/kg in the evening.

The researchers compared outcomes in 216 patients in the STRIDE Registry with participants in a randomized controlled phase 3 study of ataluren involving 228 boys, aged 7-16, who received ataluren (n = 114) or placebo (n = 114) for 48 weeks. Patients were an average 9 years old in STRIDE and in both arms of the randomized controlled trial.

The STRIDE Registry participants, comprising 184 ambulatory and 26 nonambulatory patients at enrollment, had at least 48 weeks between their first and last assessment. All of the patients in the phase 3 study and 88.6% of the STRIDE Registry patients were receiving corticosteroids along with ataluren. The researchers compared the 184 ambulatory STRIDE participants with the participants of the randomized controlled trial for one primary and four secondary endpoints from baseline to 48 weeks.

For the primary endpoint, 6-minute walk distance, average distance was 35 meters shorter than baseline in STRIDE Registry participants (n = 66), 42.2 meters shorter in the patients receiving ataluren in the phase 3 study (n = 109), and 57.6 meters shorter in RCT patients receiving placebo in the phase 3 trial (n = 109).

A secondary endpoint, the time it took patients to walk or run 10 meters, increased 1.6 seconds from baseline to 48 weeks in STRIDE Registry participants (n = 61), 2.3 seconds in participants receiving ataluren in the phase 3 trial (n = 109), and 3.5 seconds in study participants receiving placebo (n = 110).

Another secondary endpoint, the change in time it took for patients to stand from supine position from baseline to 48 weeks, was 2.9 additional seconds for STRIDE participants (n = 55), 3.8 additional seconds in study participants receiving ataluren (n = 101), and 3.9 additional seconds in study participants receiving placebo (n = 96).

Two final secondary endpoints were the changes in time to climb four stairs and to descend four stairs from baseline to 48 weeks. STRIDE participants (n = 47) climbed four stairs 1.2 seconds more slowly at 48 weeks, compared with 2.7 seconds more slowly in the participants who received ataluren in the phase 3 trial (n = 105) and 4.5 seconds more slowly in those who received placebo. Descending four stairs took 0.5 more seconds at 48 weeks in STRIDE participants (n = 40), 2.2 more seconds in participants who received ataluren in the phase 3 trial (n = 106), and 4.0 more seconds in those who received placebo (n = 100).

At least one adverse event occurred in 20.7% of registry participants; seven of these were considered treatment related. Treatment-related side effects included abdominal pain, vomiting, headache, stomach ache, diarrhea, and increased serum lipids.

The study and STRIDE Registry is funded by PTC Therapeutics with TREAT-NMD and the Cooperative International Neuromuscular Research Group. Mr. Delage and five other authors are employees of PTC Therapeutics, and six authors had received speaker or consultancy fees or served on the advisory board of a variety of companies.

SOURCE: Delage A et al. AANEM 2019, Abstract 115.
 

AUSTIN, TEX. – Real-world effectiveness of ataluren for the treatment of Duchenne muscular dystrophy (DMD) with nonsense mutation was similar to the benefit seen in the randomized controlled trial that led to its European approval, according to new data.

“Participants in the STRIDE Registry [real-world patients] showed a reduction in functional decline over 48 weeks, compared with patients receiving placebo” in the trial, reported Abdallah Delage of PTC Therapeutics in Zug, Switzerland, and his associates.

Duchenne muscular dystrophy affects an estimated 1 in 3,600-6,000 male births globally, about 10%-15% of whom have nonsense mutation DMD. This mutation causes a truncated, nonfunctional dystrophin protein due to a premature stop codon, the authors explained. Ataluren “promotes ribosomal read-through of the premature stop codon to produce a full-length dystrophin protein,” they explained.

Ataluren is currently approved for ambulatory patients age 2 and older with nonsense mutation DMD in the European Union and several other European countries. Israel, Korea, Chile, and Ukraine have approved it for patients aged 5 and older.

The Strategic Targeting of Registries and International Database of Excellence (STRIDE) Registry contains real-world data from patients using ataluren as part of an ongoing multicenter observational postapproval safety study. The investigators are tracking patients for at least 5 years after enrollment in 14 countries where ataluren is approved or commercially available through early-access programs. Patients take 40 mg/kg daily: 10 mg/kg in the morning, 10 mg/kg midday, and 20 mg/kg in the evening.

The researchers compared outcomes in 216 patients in the STRIDE Registry with participants in a randomized controlled phase 3 study of ataluren involving 228 boys, aged 7-16, who received ataluren (n = 114) or placebo (n = 114) for 48 weeks. Patients were an average 9 years old in STRIDE and in both arms of the randomized controlled trial.

The STRIDE Registry participants, comprising 184 ambulatory and 26 nonambulatory patients at enrollment, had at least 48 weeks between their first and last assessment. All of the patients in the phase 3 study and 88.6% of the STRIDE Registry patients were receiving corticosteroids along with ataluren. The researchers compared the 184 ambulatory STRIDE participants with the participants of the randomized controlled trial for one primary and four secondary endpoints from baseline to 48 weeks.

For the primary endpoint, 6-minute walk distance, average distance was 35 meters shorter than baseline in STRIDE Registry participants (n = 66), 42.2 meters shorter in the patients receiving ataluren in the phase 3 study (n = 109), and 57.6 meters shorter in RCT patients receiving placebo in the phase 3 trial (n = 109).

A secondary endpoint, the time it took patients to walk or run 10 meters, increased 1.6 seconds from baseline to 48 weeks in STRIDE Registry participants (n = 61), 2.3 seconds in participants receiving ataluren in the phase 3 trial (n = 109), and 3.5 seconds in study participants receiving placebo (n = 110).

Another secondary endpoint, the change in time it took for patients to stand from supine position from baseline to 48 weeks, was 2.9 additional seconds for STRIDE participants (n = 55), 3.8 additional seconds in study participants receiving ataluren (n = 101), and 3.9 additional seconds in study participants receiving placebo (n = 96).

Two final secondary endpoints were the changes in time to climb four stairs and to descend four stairs from baseline to 48 weeks. STRIDE participants (n = 47) climbed four stairs 1.2 seconds more slowly at 48 weeks, compared with 2.7 seconds more slowly in the participants who received ataluren in the phase 3 trial (n = 105) and 4.5 seconds more slowly in those who received placebo. Descending four stairs took 0.5 more seconds at 48 weeks in STRIDE participants (n = 40), 2.2 more seconds in participants who received ataluren in the phase 3 trial (n = 106), and 4.0 more seconds in those who received placebo (n = 100).

At least one adverse event occurred in 20.7% of registry participants; seven of these were considered treatment related. Treatment-related side effects included abdominal pain, vomiting, headache, stomach ache, diarrhea, and increased serum lipids.

The study and STRIDE Registry is funded by PTC Therapeutics with TREAT-NMD and the Cooperative International Neuromuscular Research Group. Mr. Delage and five other authors are employees of PTC Therapeutics, and six authors had received speaker or consultancy fees or served on the advisory board of a variety of companies.

SOURCE: Delage A et al. AANEM 2019, Abstract 115.
 

AUSTIN, TEX. – Real-world effectiveness of ataluren for the treatment of Duchenne muscular dystrophy (DMD) with nonsense mutation was similar to the benefit seen in the randomized controlled trial that led to its European approval, according to new data.

“Participants in the STRIDE Registry [real-world patients] showed a reduction in functional decline over 48 weeks, compared with patients receiving placebo” in the trial, reported Abdallah Delage of PTC Therapeutics in Zug, Switzerland, and his associates.

Duchenne muscular dystrophy affects an estimated 1 in 3,600-6,000 male births globally, about 10%-15% of whom have nonsense mutation DMD. This mutation causes a truncated, nonfunctional dystrophin protein due to a premature stop codon, the authors explained. Ataluren “promotes ribosomal read-through of the premature stop codon to produce a full-length dystrophin protein,” they explained.

Ataluren is currently approved for ambulatory patients age 2 and older with nonsense mutation DMD in the European Union and several other European countries. Israel, Korea, Chile, and Ukraine have approved it for patients aged 5 and older.

The Strategic Targeting of Registries and International Database of Excellence (STRIDE) Registry contains real-world data from patients using ataluren as part of an ongoing multicenter observational postapproval safety study. The investigators are tracking patients for at least 5 years after enrollment in 14 countries where ataluren is approved or commercially available through early-access programs. Patients take 40 mg/kg daily: 10 mg/kg in the morning, 10 mg/kg midday, and 20 mg/kg in the evening.

The researchers compared outcomes in 216 patients in the STRIDE Registry with participants in a randomized controlled phase 3 study of ataluren involving 228 boys, aged 7-16, who received ataluren (n = 114) or placebo (n = 114) for 48 weeks. Patients were an average 9 years old in STRIDE and in both arms of the randomized controlled trial.

The STRIDE Registry participants, comprising 184 ambulatory and 26 nonambulatory patients at enrollment, had at least 48 weeks between their first and last assessment. All of the patients in the phase 3 study and 88.6% of the STRIDE Registry patients were receiving corticosteroids along with ataluren. The researchers compared the 184 ambulatory STRIDE participants with the participants of the randomized controlled trial for one primary and four secondary endpoints from baseline to 48 weeks.

For the primary endpoint, 6-minute walk distance, average distance was 35 meters shorter than baseline in STRIDE Registry participants (n = 66), 42.2 meters shorter in the patients receiving ataluren in the phase 3 study (n = 109), and 57.6 meters shorter in RCT patients receiving placebo in the phase 3 trial (n = 109).

A secondary endpoint, the time it took patients to walk or run 10 meters, increased 1.6 seconds from baseline to 48 weeks in STRIDE Registry participants (n = 61), 2.3 seconds in participants receiving ataluren in the phase 3 trial (n = 109), and 3.5 seconds in study participants receiving placebo (n = 110).

Another secondary endpoint, the change in time it took for patients to stand from supine position from baseline to 48 weeks, was 2.9 additional seconds for STRIDE participants (n = 55), 3.8 additional seconds in study participants receiving ataluren (n = 101), and 3.9 additional seconds in study participants receiving placebo (n = 96).

Two final secondary endpoints were the changes in time to climb four stairs and to descend four stairs from baseline to 48 weeks. STRIDE participants (n = 47) climbed four stairs 1.2 seconds more slowly at 48 weeks, compared with 2.7 seconds more slowly in the participants who received ataluren in the phase 3 trial (n = 105) and 4.5 seconds more slowly in those who received placebo. Descending four stairs took 0.5 more seconds at 48 weeks in STRIDE participants (n = 40), 2.2 more seconds in participants who received ataluren in the phase 3 trial (n = 106), and 4.0 more seconds in those who received placebo (n = 100).

At least one adverse event occurred in 20.7% of registry participants; seven of these were considered treatment related. Treatment-related side effects included abdominal pain, vomiting, headache, stomach ache, diarrhea, and increased serum lipids.

The study and STRIDE Registry is funded by PTC Therapeutics with TREAT-NMD and the Cooperative International Neuromuscular Research Group. Mr. Delage and five other authors are employees of PTC Therapeutics, and six authors had received speaker or consultancy fees or served on the advisory board of a variety of companies.

SOURCE: Delage A et al. AANEM 2019, Abstract 115.
 

AUSTIN, TEX. – Patients with chronic inflammatory demyelinating polyneuropathy (CIDP) who receive intravenous immunoglobulin (IVIg) appear to have an increased risk of thromboembolic events if it is administered with a central venous access device (CVAD) when compared against those without a CVAD, according to a recent study.

Although CVADs can reliably deliver IVIg, they also represent an established risk factor for thromboembolic events, Ami Patel, PhD, a senior epidemiologist at CSL Behring, and colleagues noted on their poster at the annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine.

The results suggest a need for physicians to be vigilant about patients’ potential risk factors for thromboembolic events, Dr. Patel said in an interview. Further research is planned, however, because the current study did not control for other risk factors or explore other possible confounding, she said.

Dr. Patel and her associates analyzed U.S. claims data (IBM/Truven MarketScan) from 2006 to 2018 and included all patients with a CIDP diagnosis claim and a postdiagnosis code for IVIg. A code for CVAD up to 2 months before CIDP diagnosis without removal before IVIg treatment ended determined those with CVAD exposure, and thromboembolic events included any codes related to arterial, venous, or vascular prostheses.

The researchers then compared patients in a case-control fashion, matching each one with a CVAD to five patients of similar demographics without a CVAD. Characteristics used for matching included medical insurance type, prescription data availability, sex, age, geographic region, and years enrolled in the database.

Among 7,447 patients with at least one IVIg claim, 11.8% (n = 882) had CVAD exposure and 88.2% (n = 6,565) did not. Of those without a CVAD, 3,642 patients were matched to patients with CVAD. A quarter (25.4%) of patients with a CVAD had a thromboembolic event, compared with 11.2% of matched patients without CVADs (P less than .0001).

In the year leading up to IVIg therapy, 16.9% of those with a CVAD and 10.9% of matched patients without one had a previous thromboembolic event (P less than .0001). Patients with a CVAD also had significantly higher rates of hypertension (51.9% vs. 45.0% with placebo; P less than .001) and anticoagulation therapy (7.0% vs. 5.2% with placebo; P less than .05). Differences between the groups were not significant for diabetes (26.9% vs. 24.2%) and hyperlipidemia (19.1% vs. 17.8%).

Occlusion and stenosis of the carotid artery was the most common arterial thromboembolic outcome, occurring in 5.3% of those with a CVAD and in 2.8% of those without a CVAD. The most common venous thromboembolic event was acute venous embolism and thrombosis of lower-extremity deep vessels, which occurred in 7% of those with a CVAD and in 1.8% of those without.

The researchers also compared inpatient admissions and emergency department visits among those with and without a CVAD; both rates were higher in patients with a CVAD. Visits to the emergency department occurred at a rate of 0.14 events per month for those with a CVAD (2.01 distinct months with a claim) and 0.09 events per month for those without a CVAD (0.65 distinct months with a claim). Patients with a CVAD had 1.44 months with an inpatient admissions claim, in comparison with 0.41 months among matched patients without a CVAD. Inpatient admission frequency per month was 0.14 for those with a CVAD and 0.08 for those without.

The research was funded by CSL Behring. Dr. Patel and two of the other five authors are employees of CSL Behring.

SOURCE: Patel A et al. AANEM 2019, Abstract 94.

AUSTIN, TEX. – Patients with chronic inflammatory demyelinating polyneuropathy (CIDP) who receive intravenous immunoglobulin (IVIg) appear to have an increased risk of thromboembolic events if it is administered with a central venous access device (CVAD) when compared against those without a CVAD, according to a recent study.

Although CVADs can reliably deliver IVIg, they also represent an established risk factor for thromboembolic events, Ami Patel, PhD, a senior epidemiologist at CSL Behring, and colleagues noted on their poster at the annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine.

The results suggest a need for physicians to be vigilant about patients’ potential risk factors for thromboembolic events, Dr. Patel said in an interview. Further research is planned, however, because the current study did not control for other risk factors or explore other possible confounding, she said.

Dr. Patel and her associates analyzed U.S. claims data (IBM/Truven MarketScan) from 2006 to 2018 and included all patients with a CIDP diagnosis claim and a postdiagnosis code for IVIg. A code for CVAD up to 2 months before CIDP diagnosis without removal before IVIg treatment ended determined those with CVAD exposure, and thromboembolic events included any codes related to arterial, venous, or vascular prostheses.

The researchers then compared patients in a case-control fashion, matching each one with a CVAD to five patients of similar demographics without a CVAD. Characteristics used for matching included medical insurance type, prescription data availability, sex, age, geographic region, and years enrolled in the database.

Among 7,447 patients with at least one IVIg claim, 11.8% (n = 882) had CVAD exposure and 88.2% (n = 6,565) did not. Of those without a CVAD, 3,642 patients were matched to patients with CVAD. A quarter (25.4%) of patients with a CVAD had a thromboembolic event, compared with 11.2% of matched patients without CVADs (P less than .0001).

In the year leading up to IVIg therapy, 16.9% of those with a CVAD and 10.9% of matched patients without one had a previous thromboembolic event (P less than .0001). Patients with a CVAD also had significantly higher rates of hypertension (51.9% vs. 45.0% with placebo; P less than .001) and anticoagulation therapy (7.0% vs. 5.2% with placebo; P less than .05). Differences between the groups were not significant for diabetes (26.9% vs. 24.2%) and hyperlipidemia (19.1% vs. 17.8%).

Occlusion and stenosis of the carotid artery was the most common arterial thromboembolic outcome, occurring in 5.3% of those with a CVAD and in 2.8% of those without a CVAD. The most common venous thromboembolic event was acute venous embolism and thrombosis of lower-extremity deep vessels, which occurred in 7% of those with a CVAD and in 1.8% of those without.

The researchers also compared inpatient admissions and emergency department visits among those with and without a CVAD; both rates were higher in patients with a CVAD. Visits to the emergency department occurred at a rate of 0.14 events per month for those with a CVAD (2.01 distinct months with a claim) and 0.09 events per month for those without a CVAD (0.65 distinct months with a claim). Patients with a CVAD had 1.44 months with an inpatient admissions claim, in comparison with 0.41 months among matched patients without a CVAD. Inpatient admission frequency per month was 0.14 for those with a CVAD and 0.08 for those without.

The research was funded by CSL Behring. Dr. Patel and two of the other five authors are employees of CSL Behring.

SOURCE: Patel A et al. AANEM 2019, Abstract 94.

AUSTIN, TEX. – Patients with chronic inflammatory demyelinating polyneuropathy (CIDP) who receive intravenous immunoglobulin (IVIg) appear to have an increased risk of thromboembolic events if it is administered with a central venous access device (CVAD) when compared against those without a CVAD, according to a recent study.

Although CVADs can reliably deliver IVIg, they also represent an established risk factor for thromboembolic events, Ami Patel, PhD, a senior epidemiologist at CSL Behring, and colleagues noted on their poster at the annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine.

The results suggest a need for physicians to be vigilant about patients’ potential risk factors for thromboembolic events, Dr. Patel said in an interview. Further research is planned, however, because the current study did not control for other risk factors or explore other possible confounding, she said.

Dr. Patel and her associates analyzed U.S. claims data (IBM/Truven MarketScan) from 2006 to 2018 and included all patients with a CIDP diagnosis claim and a postdiagnosis code for IVIg. A code for CVAD up to 2 months before CIDP diagnosis without removal before IVIg treatment ended determined those with CVAD exposure, and thromboembolic events included any codes related to arterial, venous, or vascular prostheses.

The researchers then compared patients in a case-control fashion, matching each one with a CVAD to five patients of similar demographics without a CVAD. Characteristics used for matching included medical insurance type, prescription data availability, sex, age, geographic region, and years enrolled in the database.

Among 7,447 patients with at least one IVIg claim, 11.8% (n = 882) had CVAD exposure and 88.2% (n = 6,565) did not. Of those without a CVAD, 3,642 patients were matched to patients with CVAD. A quarter (25.4%) of patients with a CVAD had a thromboembolic event, compared with 11.2% of matched patients without CVADs (P less than .0001).

In the year leading up to IVIg therapy, 16.9% of those with a CVAD and 10.9% of matched patients without one had a previous thromboembolic event (P less than .0001). Patients with a CVAD also had significantly higher rates of hypertension (51.9% vs. 45.0% with placebo; P less than .001) and anticoagulation therapy (7.0% vs. 5.2% with placebo; P less than .05). Differences between the groups were not significant for diabetes (26.9% vs. 24.2%) and hyperlipidemia (19.1% vs. 17.8%).

Occlusion and stenosis of the carotid artery was the most common arterial thromboembolic outcome, occurring in 5.3% of those with a CVAD and in 2.8% of those without a CVAD. The most common venous thromboembolic event was acute venous embolism and thrombosis of lower-extremity deep vessels, which occurred in 7% of those with a CVAD and in 1.8% of those without.

The researchers also compared inpatient admissions and emergency department visits among those with and without a CVAD; both rates were higher in patients with a CVAD. Visits to the emergency department occurred at a rate of 0.14 events per month for those with a CVAD (2.01 distinct months with a claim) and 0.09 events per month for those without a CVAD (0.65 distinct months with a claim). Patients with a CVAD had 1.44 months with an inpatient admissions claim, in comparison with 0.41 months among matched patients without a CVAD. Inpatient admission frequency per month was 0.14 for those with a CVAD and 0.08 for those without.

The research was funded by CSL Behring. Dr. Patel and two of the other five authors are employees of CSL Behring.

SOURCE: Patel A et al. AANEM 2019, Abstract 94.

AUSTIN, TEX. – A three-drug combination agent called PXT3003 led to an improvement in symptoms for patients with Charcot-Marie-Tooth (CMT) disease type 1A, according to new research.

“The study has established for the first time that patients after up to 15 months of treatment had a statistically significant and clinically relevant disability improvement as illustrated by the change from baseline of their ONLS [Overall Neurology Limitations Scale] scale,” concluded Florian Thomas, MD, PhD, of Hackensack (N.J.) University Medical Center, and his associates at Pharnext. “PXT3003 with dose 4 has at least stabilized, even improved, the disease.”

The researchers presented their findings in a poster at the annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine.

The PLEO-CMT study was an international, multicenter, randomized, double-blind, placebo-controlled, phase 3 trial that evaluated the efficacy and safety of PXT3003, an oral 3-drug combination, for CMT1A. CMT1A neuropathy, occurring in an estimated 1 in 5,000 people, is characterized by distal muscle atrophy that affects walking and causes stocking-glove sensory loss and lower quality of life.

The trial enrolled 323 patients, aged 16-65, who had mild to moderate CMT1A that had been genetically confirmed. The modified full set analysis (n = 235), which represented the main study analysis for the primary endpoint, included a placebo group of 87 participants while two other groups received one of two doses of the fixed-dose drug combination twice daily: Ninety-three participants received 3 mg baclofen, 0.35 mg naltrexone, and 105 mg sorbitol (dose 1), and 55 participants received twice that dose (dose 2).

The primary endpoint was mean change from baseline to 12 and 15 months on the ONLS. At baseline, 90% of patients had an ONLS score of 2-4, and the researchers determined an average 0.3 points reduction to be a clinically meaningful effect.

Secondary endpoints included the 10-meter walk test, the 9-hole peg test, and a subscore of Charcot-Marie-Tooth neuropathy score version 2 (CMTNSv2).

Only those taking the higher dose (dose 2) showed a clinically significant drop in ONLS, –0.37 points, compared with those taking placebo (P = .0008). The in-group change from baseline to 15 months in ONLS score for patients taking dose 2 showed a trend of improvement that did not reach significance (–0.20; P = .098).

Participants receiving dose 2 of PXT3003 also walked 0.47 seconds faster on the 10-meter walk test, compared with those receiving placebo (P = .016). No significant differences occurred in the other secondary endpoints, although nonsignificant trends of improvement occurred.

Treatment-emergent adverse events were similar across all three groups and led to trial withdrawal at similar rates for dose 1 (5.5%), dose 2 (5.3%), and placebo (5.9%). One serious adverse event, benign thyroid adenoma, led to trial withdrawal, but no serious adverse events occurred related to the treatment.

Pharnext funded the research. Dr. Thomas is a researcher with Pharnext and Acceleron and has received speaking or advisory board fees from Novartis, Acceleron, Sanofi, and Genentech. The other seven authors are employees of Pharnext.

SOURCE: Thomas F et al. AANEM 2019, Abstract 92.

AUSTIN, TEX. – A three-drug combination agent called PXT3003 led to an improvement in symptoms for patients with Charcot-Marie-Tooth (CMT) disease type 1A, according to new research.

“The study has established for the first time that patients after up to 15 months of treatment had a statistically significant and clinically relevant disability improvement as illustrated by the change from baseline of their ONLS [Overall Neurology Limitations Scale] scale,” concluded Florian Thomas, MD, PhD, of Hackensack (N.J.) University Medical Center, and his associates at Pharnext. “PXT3003 with dose 4 has at least stabilized, even improved, the disease.”

The researchers presented their findings in a poster at the annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine.

The PLEO-CMT study was an international, multicenter, randomized, double-blind, placebo-controlled, phase 3 trial that evaluated the efficacy and safety of PXT3003, an oral 3-drug combination, for CMT1A. CMT1A neuropathy, occurring in an estimated 1 in 5,000 people, is characterized by distal muscle atrophy that affects walking and causes stocking-glove sensory loss and lower quality of life.

The trial enrolled 323 patients, aged 16-65, who had mild to moderate CMT1A that had been genetically confirmed. The modified full set analysis (n = 235), which represented the main study analysis for the primary endpoint, included a placebo group of 87 participants while two other groups received one of two doses of the fixed-dose drug combination twice daily: Ninety-three participants received 3 mg baclofen, 0.35 mg naltrexone, and 105 mg sorbitol (dose 1), and 55 participants received twice that dose (dose 2).

The primary endpoint was mean change from baseline to 12 and 15 months on the ONLS. At baseline, 90% of patients had an ONLS score of 2-4, and the researchers determined an average 0.3 points reduction to be a clinically meaningful effect.

Secondary endpoints included the 10-meter walk test, the 9-hole peg test, and a subscore of Charcot-Marie-Tooth neuropathy score version 2 (CMTNSv2).

Only those taking the higher dose (dose 2) showed a clinically significant drop in ONLS, –0.37 points, compared with those taking placebo (P = .0008). The in-group change from baseline to 15 months in ONLS score for patients taking dose 2 showed a trend of improvement that did not reach significance (–0.20; P = .098).

Participants receiving dose 2 of PXT3003 also walked 0.47 seconds faster on the 10-meter walk test, compared with those receiving placebo (P = .016). No significant differences occurred in the other secondary endpoints, although nonsignificant trends of improvement occurred.

Treatment-emergent adverse events were similar across all three groups and led to trial withdrawal at similar rates for dose 1 (5.5%), dose 2 (5.3%), and placebo (5.9%). One serious adverse event, benign thyroid adenoma, led to trial withdrawal, but no serious adverse events occurred related to the treatment.

Pharnext funded the research. Dr. Thomas is a researcher with Pharnext and Acceleron and has received speaking or advisory board fees from Novartis, Acceleron, Sanofi, and Genentech. The other seven authors are employees of Pharnext.

SOURCE: Thomas F et al. AANEM 2019, Abstract 92.

AUSTIN, TEX. – A three-drug combination agent called PXT3003 led to an improvement in symptoms for patients with Charcot-Marie-Tooth (CMT) disease type 1A, according to new research.

“The study has established for the first time that patients after up to 15 months of treatment had a statistically significant and clinically relevant disability improvement as illustrated by the change from baseline of their ONLS [Overall Neurology Limitations Scale] scale,” concluded Florian Thomas, MD, PhD, of Hackensack (N.J.) University Medical Center, and his associates at Pharnext. “PXT3003 with dose 4 has at least stabilized, even improved, the disease.”

The researchers presented their findings in a poster at the annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine.

The PLEO-CMT study was an international, multicenter, randomized, double-blind, placebo-controlled, phase 3 trial that evaluated the efficacy and safety of PXT3003, an oral 3-drug combination, for CMT1A. CMT1A neuropathy, occurring in an estimated 1 in 5,000 people, is characterized by distal muscle atrophy that affects walking and causes stocking-glove sensory loss and lower quality of life.

The trial enrolled 323 patients, aged 16-65, who had mild to moderate CMT1A that had been genetically confirmed. The modified full set analysis (n = 235), which represented the main study analysis for the primary endpoint, included a placebo group of 87 participants while two other groups received one of two doses of the fixed-dose drug combination twice daily: Ninety-three participants received 3 mg baclofen, 0.35 mg naltrexone, and 105 mg sorbitol (dose 1), and 55 participants received twice that dose (dose 2).

The primary endpoint was mean change from baseline to 12 and 15 months on the ONLS. At baseline, 90% of patients had an ONLS score of 2-4, and the researchers determined an average 0.3 points reduction to be a clinically meaningful effect.

Secondary endpoints included the 10-meter walk test, the 9-hole peg test, and a subscore of Charcot-Marie-Tooth neuropathy score version 2 (CMTNSv2).

Only those taking the higher dose (dose 2) showed a clinically significant drop in ONLS, –0.37 points, compared with those taking placebo (P = .0008). The in-group change from baseline to 15 months in ONLS score for patients taking dose 2 showed a trend of improvement that did not reach significance (–0.20; P = .098).

Participants receiving dose 2 of PXT3003 also walked 0.47 seconds faster on the 10-meter walk test, compared with those receiving placebo (P = .016). No significant differences occurred in the other secondary endpoints, although nonsignificant trends of improvement occurred.

Treatment-emergent adverse events were similar across all three groups and led to trial withdrawal at similar rates for dose 1 (5.5%), dose 2 (5.3%), and placebo (5.9%). One serious adverse event, benign thyroid adenoma, led to trial withdrawal, but no serious adverse events occurred related to the treatment.

Pharnext funded the research. Dr. Thomas is a researcher with Pharnext and Acceleron and has received speaking or advisory board fees from Novartis, Acceleron, Sanofi, and Genentech. The other seven authors are employees of Pharnext.

SOURCE: Thomas F et al. AANEM 2019, Abstract 92.

NEW ORLEANS – One of the most important things pediatricians can do to support their lesbian, gay, bisexual, transgender (LGBT) and other gender-nonconforming patients is to ask all their patients about their feelings, preferences and experiences when it comes to gender and sexuality, according to Julie Finger, MD, MPH.

It’s equally important not to make assumptions, she told attendees at the annual meeting of the American Academy of Pediatrics. Biology and sexual and gender identity and expression can be very diverse, she said. Specifically, doctors should not assume patients are heterosexual, that bisexuality is a phase, that orientation or attraction translates directly to behavior or vice versa, or that LGBTQ patients have unsupportive families or are engaging in risky behavior. Research suggests LGB youth have slightly higher rates of early sexual debut, sexual activity or multiple partners than straight or uncertain youth, but only marginally so.

Pediatricians also cannot assume a patient’s sexual orientation based on their partner’s gender or determine a patient’s sexual orientation or gender identity based on appearance – or even that either is the same as it was on the previous visit.

What doctors can be sure of is that they do have LGBTQ patients, said Dr. Finger, and assistant professor of clinical pediatrics at Tulane University in New Orleans. According to a 2016 Morbidity and Mortality Weekly Report (2016 Aug 12; 65[9]), about 1 in 10 students in grades 9-12 are a sexual minority. About 2% of respondents identify as gay or lesbian, 6% identify as bisexual and 3% say they aren’t sure.

Knowing the terminology

Dr. Finger defined key terminology regarding gender and sexuality. She first clarified that LGBT is not the full spectrum for sexual orientation. Pansexual (fluid attraction to any sex or gender) and asexual (lack of feeling sexual attraction) can also describe sexuality, and the Q on the end of LGBTQ is often an umbrella term for “queer” or “questioning” that encompasses anyone who fits outside conventional social norms of sexual identity and gender expression.

Sexual behaviors – which include “young men who have sex with men” and “young women who have sex with women” – do not necessarily correspond as one might expect with sexual orientation or identity, which is one’s concept of their romantic or sexual feelings, attractions and desires, again reinforcing the importance of asking patients their identity and preferences.

In terms of gender, a person’s natal or biologic gender is the one assigned people at birth based on their body parts and hormones. Gender identity is a person’s understanding of their own gender, and gender expression refers to how someone acts or presents themselves and communicates their gender within their culture.

Those who identify as “gender nonconforming, genderqueer, gender fluid, or nonbinary” see their gender on a spectrum, not within the binary “male” or “female.” A cisgender person’s gender identity matches both their biological sex assigned at birth and conventional cultural norms, while a transgender person’s gender differs from the sex they were assigned at birth. Transgender women (male to female, MTF) and men (female to men, FTM) go through the process of transition, a time that can occur in weeks or years when they shift from living as one gender to another.

While it’s unclear what leads to a person’s sexual orientation – likely a combination of genetic, hormonal and environmental factors—there is no question that sexual orientation is not a “choice,” Dr Finger said. Research has also clarified that one’s sexual orientation does not result from parenting behaviors or a history of sexual abuse.

“But I would urge all of you, instead of focusing on why someone is LGBTQ, to focus on what that means for them in their life,” Dr Finger said. “How is this bearing out in terms of their relationships and their behaviors, and how do they feel about it? How are they being supported by their family or their community, and how is it impacting their lives?”

She cited findings from a Human Rights Campaign survey in 2012 of 10,000 youth aged 13-17, which found that most LGBTQ respondents became aware of their same-sex attraction at 9 years of age, though the average age of disclosures is 16, an improvement from age 21 in the 1980s.
 

How and what to ask

Although children start becoming conscious of gender at ages 1-2, their sense of gender usually stabilizes by age 4.

“Who should we be screening for gender nonconformity? Quite frankly, all children, because all of them have some gender identity, so we should be asking them about that,” Dr Finger said.

When children are younger, doctors can ask parents about their child’s social interactions, forms of play, dress preferences, and mood. Questions for patients themselves, adapted for their age, might include, “Do you feel more like a girl, boy, neither or both?”, “How would you like to play, cut your hair and dress?” And “What name or pronoun (he or she) fits you?”

While such conversations do not necessarily need to happen annually, doctors should especially ask youth who dress or behave in non–gender-conforming ways or who appear to have mood, behavior or social difficulties.

To understand a patient’s sexuality, ask whether they are attracted to people of their own gender or sex, a different gender or sex, both or all genders or no one, or if they’re not sure yet. Doctors can then ask how comfortable they are with their attraction and whether they have told family members or friends about them.

Sexual behavior questions should be developmentally appropriate and lead to counsel but not judgment, Dr Finger said. Her method, with adjustments for age and development, starts, “There are many way of being sexual or intimate with someone: kissing, hugging and touching, and oral sex, anal sex and vaginal sex. Have you ever had any of these experiences? Which ones? With males or females or both, or other genders?”

Then she gets more specific while remaining sensitive. Doctors can ask younger children if they have held hands or cuddled with someone, if they have kissed someone, or if they have touched another person’s private parts. They can ask teens about oral sex, vaginal sex and anal sex and then gather more details about what parts went where, which helps determine what screenings or treatment options a patient may need or desire.

Doctors can use their judgment about whether to ask questions with parents in the room or not, but as kids grow older, it’s good practice to speak to patients without their caregivers present. Doctors should also explain the rules of confidentiality to their patients and be aware of the risks of “coming out,” including family discord or rejection, problems at school or work, social stigma, bullying and harassment, physical violence and risk-taking behaviors, such as substance use, self-injury and risky sexual behaviors. A HEADSSS screen can help doctors learn if any of these are present.
 

Making your practice inclusive and welcoming

Fewer than one in five teens who are “out” as LGBTQ have come out to their doctor, Dr Finger cited. Most are out to their friends and classmates, and more than half are out to their family, but teens are less likely to tell their doctors.

Research suggests one reason for this is the fact that pediatricians often don’t ask. One study found that only 20% of pediatricians discussed sexual orientation with their patients (Pediatrics 2010 Apr;125:e741-7). Similarly, only 30% of family physicians brought up sexual orientation, found another study (Fam. Med. 2001 May;33[5]:376-81). The studies found physicians more often discussed condoms, HIV, sexually transmitted infections, abstinence, violence, contraception or, in the case of family physicians, sexual behaviors, and relationships.

But another reason for not being out to doctors is a history of poor experiences. A Lambda Legal Survey in 2009 of 4,916 LGBT respondents found that 8% of LGB and 27% of transgender and gender nonconforming patients had been denied care because of their identity of orientation. Eleven percent said “providers refused to touch them or used excessive precautions,” Dr Finger reported. LGBTQ patients may fear the doctor’s reaction or not keeping their identity confidential. Patients may also have internalized shame or guilt due to societal norms or homophobia, and all these barriers can reduce LGBTQ people’s willingness to seek and access to competent care.

The first step to making LGBTQ patients comfortable in your practice is to confront your own personal biases, Dr Finger said. Understand what they are and that a provider’s discomfort, even unconscious, can be damaging to the patient-provider relationship.

“If you find that this is just not something that you’re going to be comfortable doing, at the very least, I would suggest that you find providers in your area who are comfortable working with this patient population and you refer your patients to them so that they can have a good, trusting patient-provider relationship with somebody who can provide the care that they need,” Dr Finger said.

The next step is creating a safe place with zero tolerance for insensitivity by training staff to be welcoming and inclusive, assuring patients confidentiality, providing support and resources and displaying LGBTQ-affirming materials. These youth need active, visible evidence that the office will be a safe place for them.

Ways pediatricians can communicate an inclusive environment include having gender-neutral restrooms, using “parent” instead of “mother/father” and using forms and EMR prompts with gender-neutral language or multiple options for gender selection.
 

Screening and LGBTQ patients’ health needs

LGB youth and those who aren’t sure of their sexual orientation tend to have higher rates of substance use, including tobacco, alcohol and illicit drugs, and are more often victims of rape and other sexual violence. Their rates of depressive symptoms, bullying victimization, and suicidality are also significantly higher than in their heterosexual cisgender peers. Homelessness rates are also considerably higher in LGBTQ youth than in heterosexual cisgender youth.

One thing pediatricians can do is work with parents to ensure a patient’s school is meeting their needs. The greater risks LGBTQ youth typically face are mediated by social support, resiliency, supportive friends and family and a supportive school environment, including inclusive curricula and supportive staff.

Lesbian and bisexual women are considerably more at risk for poor sexual or reproductive outcomes, Dr Finger said. Their rates of unplanned pregnancy are double that of straight women, contributing to their higher rates of emergency contraception and abortion. They are also more likely to have more partners (male and females), to have a younger sexual debut and to be forced into sex by a male partner—yet they are far less likely to perceive themselves as at risk for a sexually transmitted infection than their peers.

This patient population therefore may need contraception counseling, including discussing their current methods and reviewing their options, including emergency contraception and possibly an advance prescription. Dr Finger also suggests having male and female condoms available in the office.

Doctors should screen all their female patients, regardless of sexuality, for chlamydia and gonorrhea, and offer routine cervical cancer screening and the HPV vaccine, as recommended by the CDC. They might consider screening for trichomoniasis, bacterial vaginosis, herpes simplex, human papillomavirus and HIV.

For men who have sex with men, the CDC recommends HIV and syphilis serology, urine/pharyngeal/rectal gonorrhea nucleic acid amplification test (NAAT), urine/rectal chlamydia NAAT, and hepatitis C screening for those who are HIV-positive—all at least once a year.

For transgender patients, doctors need to assess their STI- and HIV-related risks based on their current anatomy and sexual behaviors.

Doctors should also consider discussing pre-exposure prophylaxis (PrEP) for any youth at high risk for HIV infection if they are at least 77 pounds (35 kg). Emtricitabine/tenofovir (Truvada, Descovy) reduces the chance of sexually acquired infection by 99%, and infection acquired via drug injection by 74% when taken as prescribed.

Resources

Dr Finger noted a range of resources for LGBTQ youth and their families and providers, including the Family Acceptance Project, Gay and Lesbian Medical Association, Gay, Lesbian and Straight Education Network, GLBTQ Legal Advocates and Defenders (GLAD), Human Rights Campaign, It Gets Better Project, LGBTQ Student Resources and Support, National Center for Lesbian Rights, Parents and Friends of Lesbians and Gays (PFLAG), Safe Schools Coalition and The Trevor Project (concerning suicide risk).

NEW ORLEANS – One of the most important things pediatricians can do to support their lesbian, gay, bisexual, transgender (LGBT) and other gender-nonconforming patients is to ask all their patients about their feelings, preferences and experiences when it comes to gender and sexuality, according to Julie Finger, MD, MPH.

It’s equally important not to make assumptions, she told attendees at the annual meeting of the American Academy of Pediatrics. Biology and sexual and gender identity and expression can be very diverse, she said. Specifically, doctors should not assume patients are heterosexual, that bisexuality is a phase, that orientation or attraction translates directly to behavior or vice versa, or that LGBTQ patients have unsupportive families or are engaging in risky behavior. Research suggests LGB youth have slightly higher rates of early sexual debut, sexual activity or multiple partners than straight or uncertain youth, but only marginally so.

Pediatricians also cannot assume a patient’s sexual orientation based on their partner’s gender or determine a patient’s sexual orientation or gender identity based on appearance – or even that either is the same as it was on the previous visit.

What doctors can be sure of is that they do have LGBTQ patients, said Dr. Finger, and assistant professor of clinical pediatrics at Tulane University in New Orleans. According to a 2016 Morbidity and Mortality Weekly Report (2016 Aug 12; 65[9]), about 1 in 10 students in grades 9-12 are a sexual minority. About 2% of respondents identify as gay or lesbian, 6% identify as bisexual and 3% say they aren’t sure.

Knowing the terminology

Dr. Finger defined key terminology regarding gender and sexuality. She first clarified that LGBT is not the full spectrum for sexual orientation. Pansexual (fluid attraction to any sex or gender) and asexual (lack of feeling sexual attraction) can also describe sexuality, and the Q on the end of LGBTQ is often an umbrella term for “queer” or “questioning” that encompasses anyone who fits outside conventional social norms of sexual identity and gender expression.

Sexual behaviors – which include “young men who have sex with men” and “young women who have sex with women” – do not necessarily correspond as one might expect with sexual orientation or identity, which is one’s concept of their romantic or sexual feelings, attractions and desires, again reinforcing the importance of asking patients their identity and preferences.

In terms of gender, a person’s natal or biologic gender is the one assigned people at birth based on their body parts and hormones. Gender identity is a person’s understanding of their own gender, and gender expression refers to how someone acts or presents themselves and communicates their gender within their culture.

Those who identify as “gender nonconforming, genderqueer, gender fluid, or nonbinary” see their gender on a spectrum, not within the binary “male” or “female.” A cisgender person’s gender identity matches both their biological sex assigned at birth and conventional cultural norms, while a transgender person’s gender differs from the sex they were assigned at birth. Transgender women (male to female, MTF) and men (female to men, FTM) go through the process of transition, a time that can occur in weeks or years when they shift from living as one gender to another.

While it’s unclear what leads to a person’s sexual orientation – likely a combination of genetic, hormonal and environmental factors—there is no question that sexual orientation is not a “choice,” Dr Finger said. Research has also clarified that one’s sexual orientation does not result from parenting behaviors or a history of sexual abuse.

“But I would urge all of you, instead of focusing on why someone is LGBTQ, to focus on what that means for them in their life,” Dr Finger said. “How is this bearing out in terms of their relationships and their behaviors, and how do they feel about it? How are they being supported by their family or their community, and how is it impacting their lives?”

She cited findings from a Human Rights Campaign survey in 2012 of 10,000 youth aged 13-17, which found that most LGBTQ respondents became aware of their same-sex attraction at 9 years of age, though the average age of disclosures is 16, an improvement from age 21 in the 1980s.
 

How and what to ask

Although children start becoming conscious of gender at ages 1-2, their sense of gender usually stabilizes by age 4.

“Who should we be screening for gender nonconformity? Quite frankly, all children, because all of them have some gender identity, so we should be asking them about that,” Dr Finger said.

When children are younger, doctors can ask parents about their child’s social interactions, forms of play, dress preferences, and mood. Questions for patients themselves, adapted for their age, might include, “Do you feel more like a girl, boy, neither or both?”, “How would you like to play, cut your hair and dress?” And “What name or pronoun (he or she) fits you?”

While such conversations do not necessarily need to happen annually, doctors should especially ask youth who dress or behave in non–gender-conforming ways or who appear to have mood, behavior or social difficulties.

To understand a patient’s sexuality, ask whether they are attracted to people of their own gender or sex, a different gender or sex, both or all genders or no one, or if they’re not sure yet. Doctors can then ask how comfortable they are with their attraction and whether they have told family members or friends about them.

Sexual behavior questions should be developmentally appropriate and lead to counsel but not judgment, Dr Finger said. Her method, with adjustments for age and development, starts, “There are many way of being sexual or intimate with someone: kissing, hugging and touching, and oral sex, anal sex and vaginal sex. Have you ever had any of these experiences? Which ones? With males or females or both, or other genders?”

Then she gets more specific while remaining sensitive. Doctors can ask younger children if they have held hands or cuddled with someone, if they have kissed someone, or if they have touched another person’s private parts. They can ask teens about oral sex, vaginal sex and anal sex and then gather more details about what parts went where, which helps determine what screenings or treatment options a patient may need or desire.

Doctors can use their judgment about whether to ask questions with parents in the room or not, but as kids grow older, it’s good practice to speak to patients without their caregivers present. Doctors should also explain the rules of confidentiality to their patients and be aware of the risks of “coming out,” including family discord or rejection, problems at school or work, social stigma, bullying and harassment, physical violence and risk-taking behaviors, such as substance use, self-injury and risky sexual behaviors. A HEADSSS screen can help doctors learn if any of these are present.
 

Making your practice inclusive and welcoming

Fewer than one in five teens who are “out” as LGBTQ have come out to their doctor, Dr Finger cited. Most are out to their friends and classmates, and more than half are out to their family, but teens are less likely to tell their doctors.

Research suggests one reason for this is the fact that pediatricians often don’t ask. One study found that only 20% of pediatricians discussed sexual orientation with their patients (Pediatrics 2010 Apr;125:e741-7). Similarly, only 30% of family physicians brought up sexual orientation, found another study (Fam. Med. 2001 May;33[5]:376-81). The studies found physicians more often discussed condoms, HIV, sexually transmitted infections, abstinence, violence, contraception or, in the case of family physicians, sexual behaviors, and relationships.

But another reason for not being out to doctors is a history of poor experiences. A Lambda Legal Survey in 2009 of 4,916 LGBT respondents found that 8% of LGB and 27% of transgender and gender nonconforming patients had been denied care because of their identity of orientation. Eleven percent said “providers refused to touch them or used excessive precautions,” Dr Finger reported. LGBTQ patients may fear the doctor’s reaction or not keeping their identity confidential. Patients may also have internalized shame or guilt due to societal norms or homophobia, and all these barriers can reduce LGBTQ people’s willingness to seek and access to competent care.

The first step to making LGBTQ patients comfortable in your practice is to confront your own personal biases, Dr Finger said. Understand what they are and that a provider’s discomfort, even unconscious, can be damaging to the patient-provider relationship.

“If you find that this is just not something that you’re going to be comfortable doing, at the very least, I would suggest that you find providers in your area who are comfortable working with this patient population and you refer your patients to them so that they can have a good, trusting patient-provider relationship with somebody who can provide the care that they need,” Dr Finger said.

The next step is creating a safe place with zero tolerance for insensitivity by training staff to be welcoming and inclusive, assuring patients confidentiality, providing support and resources and displaying LGBTQ-affirming materials. These youth need active, visible evidence that the office will be a safe place for them.

Ways pediatricians can communicate an inclusive environment include having gender-neutral restrooms, using “parent” instead of “mother/father” and using forms and EMR prompts with gender-neutral language or multiple options for gender selection.
 

Screening and LGBTQ patients’ health needs

LGB youth and those who aren’t sure of their sexual orientation tend to have higher rates of substance use, including tobacco, alcohol and illicit drugs, and are more often victims of rape and other sexual violence. Their rates of depressive symptoms, bullying victimization, and suicidality are also significantly higher than in their heterosexual cisgender peers. Homelessness rates are also considerably higher in LGBTQ youth than in heterosexual cisgender youth.

One thing pediatricians can do is work with parents to ensure a patient’s school is meeting their needs. The greater risks LGBTQ youth typically face are mediated by social support, resiliency, supportive friends and family and a supportive school environment, including inclusive curricula and supportive staff.

Lesbian and bisexual women are considerably more at risk for poor sexual or reproductive outcomes, Dr Finger said. Their rates of unplanned pregnancy are double that of straight women, contributing to their higher rates of emergency contraception and abortion. They are also more likely to have more partners (male and females), to have a younger sexual debut and to be forced into sex by a male partner—yet they are far less likely to perceive themselves as at risk for a sexually transmitted infection than their peers.

This patient population therefore may need contraception counseling, including discussing their current methods and reviewing their options, including emergency contraception and possibly an advance prescription. Dr Finger also suggests having male and female condoms available in the office.

Doctors should screen all their female patients, regardless of sexuality, for chlamydia and gonorrhea, and offer routine cervical cancer screening and the HPV vaccine, as recommended by the CDC. They might consider screening for trichomoniasis, bacterial vaginosis, herpes simplex, human papillomavirus and HIV.

For men who have sex with men, the CDC recommends HIV and syphilis serology, urine/pharyngeal/rectal gonorrhea nucleic acid amplification test (NAAT), urine/rectal chlamydia NAAT, and hepatitis C screening for those who are HIV-positive—all at least once a year.

For transgender patients, doctors need to assess their STI- and HIV-related risks based on their current anatomy and sexual behaviors.

Doctors should also consider discussing pre-exposure prophylaxis (PrEP) for any youth at high risk for HIV infection if they are at least 77 pounds (35 kg). Emtricitabine/tenofovir (Truvada, Descovy) reduces the chance of sexually acquired infection by 99%, and infection acquired via drug injection by 74% when taken as prescribed.

Resources

Dr Finger noted a range of resources for LGBTQ youth and their families and providers, including the Family Acceptance Project, Gay and Lesbian Medical Association, Gay, Lesbian and Straight Education Network, GLBTQ Legal Advocates and Defenders (GLAD), Human Rights Campaign, It Gets Better Project, LGBTQ Student Resources and Support, National Center for Lesbian Rights, Parents and Friends of Lesbians and Gays (PFLAG), Safe Schools Coalition and The Trevor Project (concerning suicide risk).

NEW ORLEANS – One of the most important things pediatricians can do to support their lesbian, gay, bisexual, transgender (LGBT) and other gender-nonconforming patients is to ask all their patients about their feelings, preferences and experiences when it comes to gender and sexuality, according to Julie Finger, MD, MPH.

It’s equally important not to make assumptions, she told attendees at the annual meeting of the American Academy of Pediatrics. Biology and sexual and gender identity and expression can be very diverse, she said. Specifically, doctors should not assume patients are heterosexual, that bisexuality is a phase, that orientation or attraction translates directly to behavior or vice versa, or that LGBTQ patients have unsupportive families or are engaging in risky behavior. Research suggests LGB youth have slightly higher rates of early sexual debut, sexual activity or multiple partners than straight or uncertain youth, but only marginally so.

Pediatricians also cannot assume a patient’s sexual orientation based on their partner’s gender or determine a patient’s sexual orientation or gender identity based on appearance – or even that either is the same as it was on the previous visit.

What doctors can be sure of is that they do have LGBTQ patients, said Dr. Finger, and assistant professor of clinical pediatrics at Tulane University in New Orleans. According to a 2016 Morbidity and Mortality Weekly Report (2016 Aug 12; 65[9]), about 1 in 10 students in grades 9-12 are a sexual minority. About 2% of respondents identify as gay or lesbian, 6% identify as bisexual and 3% say they aren’t sure.

Knowing the terminology

Dr. Finger defined key terminology regarding gender and sexuality. She first clarified that LGBT is not the full spectrum for sexual orientation. Pansexual (fluid attraction to any sex or gender) and asexual (lack of feeling sexual attraction) can also describe sexuality, and the Q on the end of LGBTQ is often an umbrella term for “queer” or “questioning” that encompasses anyone who fits outside conventional social norms of sexual identity and gender expression.

Sexual behaviors – which include “young men who have sex with men” and “young women who have sex with women” – do not necessarily correspond as one might expect with sexual orientation or identity, which is one’s concept of their romantic or sexual feelings, attractions and desires, again reinforcing the importance of asking patients their identity and preferences.

In terms of gender, a person’s natal or biologic gender is the one assigned people at birth based on their body parts and hormones. Gender identity is a person’s understanding of their own gender, and gender expression refers to how someone acts or presents themselves and communicates their gender within their culture.

Those who identify as “gender nonconforming, genderqueer, gender fluid, or nonbinary” see their gender on a spectrum, not within the binary “male” or “female.” A cisgender person’s gender identity matches both their biological sex assigned at birth and conventional cultural norms, while a transgender person’s gender differs from the sex they were assigned at birth. Transgender women (male to female, MTF) and men (female to men, FTM) go through the process of transition, a time that can occur in weeks or years when they shift from living as one gender to another.

While it’s unclear what leads to a person’s sexual orientation – likely a combination of genetic, hormonal and environmental factors—there is no question that sexual orientation is not a “choice,” Dr Finger said. Research has also clarified that one’s sexual orientation does not result from parenting behaviors or a history of sexual abuse.

“But I would urge all of you, instead of focusing on why someone is LGBTQ, to focus on what that means for them in their life,” Dr Finger said. “How is this bearing out in terms of their relationships and their behaviors, and how do they feel about it? How are they being supported by their family or their community, and how is it impacting their lives?”

She cited findings from a Human Rights Campaign survey in 2012 of 10,000 youth aged 13-17, which found that most LGBTQ respondents became aware of their same-sex attraction at 9 years of age, though the average age of disclosures is 16, an improvement from age 21 in the 1980s.
 

How and what to ask

Although children start becoming conscious of gender at ages 1-2, their sense of gender usually stabilizes by age 4.

“Who should we be screening for gender nonconformity? Quite frankly, all children, because all of them have some gender identity, so we should be asking them about that,” Dr Finger said.

When children are younger, doctors can ask parents about their child’s social interactions, forms of play, dress preferences, and mood. Questions for patients themselves, adapted for their age, might include, “Do you feel more like a girl, boy, neither or both?”, “How would you like to play, cut your hair and dress?” And “What name or pronoun (he or she) fits you?”

While such conversations do not necessarily need to happen annually, doctors should especially ask youth who dress or behave in non–gender-conforming ways or who appear to have mood, behavior or social difficulties.

To understand a patient’s sexuality, ask whether they are attracted to people of their own gender or sex, a different gender or sex, both or all genders or no one, or if they’re not sure yet. Doctors can then ask how comfortable they are with their attraction and whether they have told family members or friends about them.

Sexual behavior questions should be developmentally appropriate and lead to counsel but not judgment, Dr Finger said. Her method, with adjustments for age and development, starts, “There are many way of being sexual or intimate with someone: kissing, hugging and touching, and oral sex, anal sex and vaginal sex. Have you ever had any of these experiences? Which ones? With males or females or both, or other genders?”

Then she gets more specific while remaining sensitive. Doctors can ask younger children if they have held hands or cuddled with someone, if they have kissed someone, or if they have touched another person’s private parts. They can ask teens about oral sex, vaginal sex and anal sex and then gather more details about what parts went where, which helps determine what screenings or treatment options a patient may need or desire.

Doctors can use their judgment about whether to ask questions with parents in the room or not, but as kids grow older, it’s good practice to speak to patients without their caregivers present. Doctors should also explain the rules of confidentiality to their patients and be aware of the risks of “coming out,” including family discord or rejection, problems at school or work, social stigma, bullying and harassment, physical violence and risk-taking behaviors, such as substance use, self-injury and risky sexual behaviors. A HEADSSS screen can help doctors learn if any of these are present.
 

Making your practice inclusive and welcoming

Fewer than one in five teens who are “out” as LGBTQ have come out to their doctor, Dr Finger cited. Most are out to their friends and classmates, and more than half are out to their family, but teens are less likely to tell their doctors.

Research suggests one reason for this is the fact that pediatricians often don’t ask. One study found that only 20% of pediatricians discussed sexual orientation with their patients (Pediatrics 2010 Apr;125:e741-7). Similarly, only 30% of family physicians brought up sexual orientation, found another study (Fam. Med. 2001 May;33[5]:376-81). The studies found physicians more often discussed condoms, HIV, sexually transmitted infections, abstinence, violence, contraception or, in the case of family physicians, sexual behaviors, and relationships.

But another reason for not being out to doctors is a history of poor experiences. A Lambda Legal Survey in 2009 of 4,916 LGBT respondents found that 8% of LGB and 27% of transgender and gender nonconforming patients had been denied care because of their identity of orientation. Eleven percent said “providers refused to touch them or used excessive precautions,” Dr Finger reported. LGBTQ patients may fear the doctor’s reaction or not keeping their identity confidential. Patients may also have internalized shame or guilt due to societal norms or homophobia, and all these barriers can reduce LGBTQ people’s willingness to seek and access to competent care.

The first step to making LGBTQ patients comfortable in your practice is to confront your own personal biases, Dr Finger said. Understand what they are and that a provider’s discomfort, even unconscious, can be damaging to the patient-provider relationship.

“If you find that this is just not something that you’re going to be comfortable doing, at the very least, I would suggest that you find providers in your area who are comfortable working with this patient population and you refer your patients to them so that they can have a good, trusting patient-provider relationship with somebody who can provide the care that they need,” Dr Finger said.

The next step is creating a safe place with zero tolerance for insensitivity by training staff to be welcoming and inclusive, assuring patients confidentiality, providing support and resources and displaying LGBTQ-affirming materials. These youth need active, visible evidence that the office will be a safe place for them.

Ways pediatricians can communicate an inclusive environment include having gender-neutral restrooms, using “parent” instead of “mother/father” and using forms and EMR prompts with gender-neutral language or multiple options for gender selection.
 

Screening and LGBTQ patients’ health needs

LGB youth and those who aren’t sure of their sexual orientation tend to have higher rates of substance use, including tobacco, alcohol and illicit drugs, and are more often victims of rape and other sexual violence. Their rates of depressive symptoms, bullying victimization, and suicidality are also significantly higher than in their heterosexual cisgender peers. Homelessness rates are also considerably higher in LGBTQ youth than in heterosexual cisgender youth.

One thing pediatricians can do is work with parents to ensure a patient’s school is meeting their needs. The greater risks LGBTQ youth typically face are mediated by social support, resiliency, supportive friends and family and a supportive school environment, including inclusive curricula and supportive staff.

Lesbian and bisexual women are considerably more at risk for poor sexual or reproductive outcomes, Dr Finger said. Their rates of unplanned pregnancy are double that of straight women, contributing to their higher rates of emergency contraception and abortion. They are also more likely to have more partners (male and females), to have a younger sexual debut and to be forced into sex by a male partner—yet they are far less likely to perceive themselves as at risk for a sexually transmitted infection than their peers.

This patient population therefore may need contraception counseling, including discussing their current methods and reviewing their options, including emergency contraception and possibly an advance prescription. Dr Finger also suggests having male and female condoms available in the office.

Doctors should screen all their female patients, regardless of sexuality, for chlamydia and gonorrhea, and offer routine cervical cancer screening and the HPV vaccine, as recommended by the CDC. They might consider screening for trichomoniasis, bacterial vaginosis, herpes simplex, human papillomavirus and HIV.

For men who have sex with men, the CDC recommends HIV and syphilis serology, urine/pharyngeal/rectal gonorrhea nucleic acid amplification test (NAAT), urine/rectal chlamydia NAAT, and hepatitis C screening for those who are HIV-positive—all at least once a year.

For transgender patients, doctors need to assess their STI- and HIV-related risks based on their current anatomy and sexual behaviors.

Doctors should also consider discussing pre-exposure prophylaxis (PrEP) for any youth at high risk for HIV infection if they are at least 77 pounds (35 kg). Emtricitabine/tenofovir (Truvada, Descovy) reduces the chance of sexually acquired infection by 99%, and infection acquired via drug injection by 74% when taken as prescribed.

Resources

Dr Finger noted a range of resources for LGBTQ youth and their families and providers, including the Family Acceptance Project, Gay and Lesbian Medical Association, Gay, Lesbian and Straight Education Network, GLBTQ Legal Advocates and Defenders (GLAD), Human Rights Campaign, It Gets Better Project, LGBTQ Student Resources and Support, National Center for Lesbian Rights, Parents and Friends of Lesbians and Gays (PFLAG), Safe Schools Coalition and The Trevor Project (concerning suicide risk).

NEW ORLEANS – Nearly half of all children with autism spectrum disorder wander off from safe supervision at some point in their childhood or adolescence, reported Paul Lipkin, MD, at the annual meeting of the American Academy of Pediatrics.

Though such behavior is developmentally normal in toddlers, it’s rarer for older children to leave a supervised, safe space for a longer period than just running away for a bit, he said.

Far more than an inconvenience, wandering, also called elopement, puts these children at high risk for injury or victimization. In fact, statistics from a survey by the National Autism Foundation suggest that nearly a third of autism-related wandering cases resulted in death or serious enough injury to require medical attention, said Dr. Lipkin, an associate professor of pediatrics at the Kennedy Krieger Institute and Johns Hopkins Medicine in Baltimore.

“Drowning is overwhelmingly the main cause of death in children with autism,” he said, sharing the data from National Autism Association, which relied on parent report and media reports. In that data, 71% of deaths from autistic children who wandered from 2011-2016 were drowning, and of those deaths, 76% of the drownings occurred in a natural body of water or drainage water. At a distant second, 18% of deaths were traffic accidents. The remaining causes were being hit by a train (4%), hypothermia or hyperthermia (3%), falling (1%) or other trauma (3%) (J Autism Dev Disord. 2019 Mar 5. doi: 10.1007/s10803-019-03961-x).

Academic research has found similar statistics to those from the National Autism Association. In one study, 53% of autistic youth who attempted to run off succeeded and were missing long enough to cause safety concerns (Pediatrics. 2012 Nov;130[5]:870-7). Among these youth – representing about a quarter of all families surveyed in the study – the police were called in 31% of cases. In addition, 65% had a “close call” with a traffic injury and 24% had a close call with drowning.

The children wandered off in various settings, including home; another’s home; a store or other public place; or school, daycare or camp. A 2019 study found that 70% of parents reported their children wandering off from home at least once in the past 2 years (J Autism Dev Disorders. 2019 Mar 5; doi: 10.1107/s10803-019-03961-x).

Although most cases occur in children and teens, with the highest rate of death among children aged 5-9, the National Autism Association has received reports of wandering occur throughout autistic people’s lifetime.

Yet this issue doesn’t appear to be on the radar of many pediatricians, and those who are aware of it may not know the best strategies to share with parents to prevent wandering and subsequent injury, Dr Lipkin explained. In one study, only one-third of parents reported receiving guidance from a health provider related to wandering (J Dev Behav Pediatr. 2018 Sep;39[7]:538-46).

That research found that only 10% received advice from a pediatrician or other primary care provider, 12% received advice from a developmental pediatrician or neurologist and 10% received advance from a psychologist or psychiatrist. The largest source of guidance in that study was autism advocacy organizations, whom 22% of parents cited. Others included a teacher or other school staff member (15%), a personal contact (13%), law enforcement (8%) or another source (1%).
 

Role of the pediatrician

Pediatricians have an important role to play in prevention of elopement, Dr Lipkin said. They can screen autistic patients for wandering and elopement during visits, work with community stakeholders such as schools and law enforcement, advocate for awareness, and provider education and resources for families.

Perhaps the most valuable resource, he said, is the Big Red Safety Box, available from the National Autism Association. This resource, sponsored by more than a half dozen autism advocacy organizations, includes three digital safety toolkits: one for caregivers, one for first responders, and one for teachers. Parents can therefore share the toolkits for first responders and teachers with those respective community members.

Pediatricians can also help families develop a Family Wandering Emergency Plan (FWEP), a template for which is in the Big Red Safety Box. Parents and community members should know the steps to take if someone wanders: Stay calm, call 911, search nearby water first and then implement the FWEP.

It’s first helpful to understand why these youth wander off. In the National Autism Association survey, the most common reasons were to escape an anxious situation, particularly for those with Asperger’s, or simply to run, explore, or go to a favorite place, particularly among those with autism or pervasive developmental disorder-not otherwise specified (PDD-NOS).

Researchers have found similar reasons: 43% of elopement situations occurred when children were trying to escape an anxious situation, 39% left while in a stressful environment, and 24% were in an environment with conflict, found one study (J Autism Dev Disord. 2019 Mar 5. doi: 10.1007/s10803-019-03961-x).

Sensory overload was also a trigger, with 38% of elopements occurring when it was too noisy, and 34% when it was a generally uncomfortable sensory experience. Just over a quarter (27%) of children left when they were understimulated or in a “boring” environment, Dr Lipkin reported. The remaining reason was goal-directed: 27% left to pursue a special interest, 18% sought a place where they enjoyed playing, and 11% were after their favorite food.
 

Prevention Strategies

Most data about effective strategies to prevent wandering comes from research that relies on parents, Dr Lipkin said. In general, environmental interventions tend to be the most effective, and medication tends to be the least effective.

One study on elopement prevention found that 96% of caregivers use at least some type of intervention, and the vast majority (83%) were using environmental interventions such as dead bolts (51%), latches (49%) and gates (36%). An equal proportion used behavioral services (83%), such as a behavioral psychologist (41%), social stories (40%) or an aide (39%). Just under a third used an ID bracelet or shoe tag (31%), and 19% used GPS trackers, according to Dr. Lipkin.

Although parents reported environmental interventions to be very effective, 68% said they were highly burdensome, though the median cost over 2 years was less than $1,000. The least expensive intervention was home behavioral specialists (when covered by insurance) and school aides, and the most expensive and burdensome – albeit highly effective – was a service animal.

Interventions with the least cost effectiveness included security cameras and GPS trackers, which only 15% of parents reported as being effective.

Although nearly half of parents reported their child had taken any psychiatric medication (48%), only 16% had taken medication explicitly to prevent wandering. Few reported the medication was very effective, however. Among the small number who did (less than 10), lorazepam, diazepam and atomoxetine appeared best.

Teaching children survival skills, as developmentally appropriate and possible, can also help. These include swimming lessons as well as learning how to interact in traffic, knowing their home address, and learning how to navigate around their neighborhood.

Dr. Lipkin no disclosures and used no external funding for this presentation.

NEW ORLEANS – Nearly half of all children with autism spectrum disorder wander off from safe supervision at some point in their childhood or adolescence, reported Paul Lipkin, MD, at the annual meeting of the American Academy of Pediatrics.

Though such behavior is developmentally normal in toddlers, it’s rarer for older children to leave a supervised, safe space for a longer period than just running away for a bit, he said.

Far more than an inconvenience, wandering, also called elopement, puts these children at high risk for injury or victimization. In fact, statistics from a survey by the National Autism Foundation suggest that nearly a third of autism-related wandering cases resulted in death or serious enough injury to require medical attention, said Dr. Lipkin, an associate professor of pediatrics at the Kennedy Krieger Institute and Johns Hopkins Medicine in Baltimore.

“Drowning is overwhelmingly the main cause of death in children with autism,” he said, sharing the data from National Autism Association, which relied on parent report and media reports. In that data, 71% of deaths from autistic children who wandered from 2011-2016 were drowning, and of those deaths, 76% of the drownings occurred in a natural body of water or drainage water. At a distant second, 18% of deaths were traffic accidents. The remaining causes were being hit by a train (4%), hypothermia or hyperthermia (3%), falling (1%) or other trauma (3%) (J Autism Dev Disord. 2019 Mar 5. doi: 10.1007/s10803-019-03961-x).

Academic research has found similar statistics to those from the National Autism Association. In one study, 53% of autistic youth who attempted to run off succeeded and were missing long enough to cause safety concerns (Pediatrics. 2012 Nov;130[5]:870-7). Among these youth – representing about a quarter of all families surveyed in the study – the police were called in 31% of cases. In addition, 65% had a “close call” with a traffic injury and 24% had a close call with drowning.

The children wandered off in various settings, including home; another’s home; a store or other public place; or school, daycare or camp. A 2019 study found that 70% of parents reported their children wandering off from home at least once in the past 2 years (J Autism Dev Disorders. 2019 Mar 5; doi: 10.1107/s10803-019-03961-x).

Although most cases occur in children and teens, with the highest rate of death among children aged 5-9, the National Autism Association has received reports of wandering occur throughout autistic people’s lifetime.

Yet this issue doesn’t appear to be on the radar of many pediatricians, and those who are aware of it may not know the best strategies to share with parents to prevent wandering and subsequent injury, Dr Lipkin explained. In one study, only one-third of parents reported receiving guidance from a health provider related to wandering (J Dev Behav Pediatr. 2018 Sep;39[7]:538-46).

That research found that only 10% received advice from a pediatrician or other primary care provider, 12% received advice from a developmental pediatrician or neurologist and 10% received advance from a psychologist or psychiatrist. The largest source of guidance in that study was autism advocacy organizations, whom 22% of parents cited. Others included a teacher or other school staff member (15%), a personal contact (13%), law enforcement (8%) or another source (1%).
 

Role of the pediatrician

Pediatricians have an important role to play in prevention of elopement, Dr Lipkin said. They can screen autistic patients for wandering and elopement during visits, work with community stakeholders such as schools and law enforcement, advocate for awareness, and provider education and resources for families.

Perhaps the most valuable resource, he said, is the Big Red Safety Box, available from the National Autism Association. This resource, sponsored by more than a half dozen autism advocacy organizations, includes three digital safety toolkits: one for caregivers, one for first responders, and one for teachers. Parents can therefore share the toolkits for first responders and teachers with those respective community members.

Pediatricians can also help families develop a Family Wandering Emergency Plan (FWEP), a template for which is in the Big Red Safety Box. Parents and community members should know the steps to take if someone wanders: Stay calm, call 911, search nearby water first and then implement the FWEP.

It’s first helpful to understand why these youth wander off. In the National Autism Association survey, the most common reasons were to escape an anxious situation, particularly for those with Asperger’s, or simply to run, explore, or go to a favorite place, particularly among those with autism or pervasive developmental disorder-not otherwise specified (PDD-NOS).

Researchers have found similar reasons: 43% of elopement situations occurred when children were trying to escape an anxious situation, 39% left while in a stressful environment, and 24% were in an environment with conflict, found one study (J Autism Dev Disord. 2019 Mar 5. doi: 10.1007/s10803-019-03961-x).

Sensory overload was also a trigger, with 38% of elopements occurring when it was too noisy, and 34% when it was a generally uncomfortable sensory experience. Just over a quarter (27%) of children left when they were understimulated or in a “boring” environment, Dr Lipkin reported. The remaining reason was goal-directed: 27% left to pursue a special interest, 18% sought a place where they enjoyed playing, and 11% were after their favorite food.
 

Prevention Strategies

Most data about effective strategies to prevent wandering comes from research that relies on parents, Dr Lipkin said. In general, environmental interventions tend to be the most effective, and medication tends to be the least effective.

One study on elopement prevention found that 96% of caregivers use at least some type of intervention, and the vast majority (83%) were using environmental interventions such as dead bolts (51%), latches (49%) and gates (36%). An equal proportion used behavioral services (83%), such as a behavioral psychologist (41%), social stories (40%) or an aide (39%). Just under a third used an ID bracelet or shoe tag (31%), and 19% used GPS trackers, according to Dr. Lipkin.

Although parents reported environmental interventions to be very effective, 68% said they were highly burdensome, though the median cost over 2 years was less than $1,000. The least expensive intervention was home behavioral specialists (when covered by insurance) and school aides, and the most expensive and burdensome – albeit highly effective – was a service animal.

Interventions with the least cost effectiveness included security cameras and GPS trackers, which only 15% of parents reported as being effective.

Although nearly half of parents reported their child had taken any psychiatric medication (48%), only 16% had taken medication explicitly to prevent wandering. Few reported the medication was very effective, however. Among the small number who did (less than 10), lorazepam, diazepam and atomoxetine appeared best.

Teaching children survival skills, as developmentally appropriate and possible, can also help. These include swimming lessons as well as learning how to interact in traffic, knowing their home address, and learning how to navigate around their neighborhood.

Dr. Lipkin no disclosures and used no external funding for this presentation.

NEW ORLEANS – Nearly half of all children with autism spectrum disorder wander off from safe supervision at some point in their childhood or adolescence, reported Paul Lipkin, MD, at the annual meeting of the American Academy of Pediatrics.

Though such behavior is developmentally normal in toddlers, it’s rarer for older children to leave a supervised, safe space for a longer period than just running away for a bit, he said.

Far more than an inconvenience, wandering, also called elopement, puts these children at high risk for injury or victimization. In fact, statistics from a survey by the National Autism Foundation suggest that nearly a third of autism-related wandering cases resulted in death or serious enough injury to require medical attention, said Dr. Lipkin, an associate professor of pediatrics at the Kennedy Krieger Institute and Johns Hopkins Medicine in Baltimore.

“Drowning is overwhelmingly the main cause of death in children with autism,” he said, sharing the data from National Autism Association, which relied on parent report and media reports. In that data, 71% of deaths from autistic children who wandered from 2011-2016 were drowning, and of those deaths, 76% of the drownings occurred in a natural body of water or drainage water. At a distant second, 18% of deaths were traffic accidents. The remaining causes were being hit by a train (4%), hypothermia or hyperthermia (3%), falling (1%) or other trauma (3%) (J Autism Dev Disord. 2019 Mar 5. doi: 10.1007/s10803-019-03961-x).

Academic research has found similar statistics to those from the National Autism Association. In one study, 53% of autistic youth who attempted to run off succeeded and were missing long enough to cause safety concerns (Pediatrics. 2012 Nov;130[5]:870-7). Among these youth – representing about a quarter of all families surveyed in the study – the police were called in 31% of cases. In addition, 65% had a “close call” with a traffic injury and 24% had a close call with drowning.

The children wandered off in various settings, including home; another’s home; a store or other public place; or school, daycare or camp. A 2019 study found that 70% of parents reported their children wandering off from home at least once in the past 2 years (J Autism Dev Disorders. 2019 Mar 5; doi: 10.1107/s10803-019-03961-x).

Although most cases occur in children and teens, with the highest rate of death among children aged 5-9, the National Autism Association has received reports of wandering occur throughout autistic people’s lifetime.

Yet this issue doesn’t appear to be on the radar of many pediatricians, and those who are aware of it may not know the best strategies to share with parents to prevent wandering and subsequent injury, Dr Lipkin explained. In one study, only one-third of parents reported receiving guidance from a health provider related to wandering (J Dev Behav Pediatr. 2018 Sep;39[7]:538-46).

That research found that only 10% received advice from a pediatrician or other primary care provider, 12% received advice from a developmental pediatrician or neurologist and 10% received advance from a psychologist or psychiatrist. The largest source of guidance in that study was autism advocacy organizations, whom 22% of parents cited. Others included a teacher or other school staff member (15%), a personal contact (13%), law enforcement (8%) or another source (1%).
 

Role of the pediatrician

Pediatricians have an important role to play in prevention of elopement, Dr Lipkin said. They can screen autistic patients for wandering and elopement during visits, work with community stakeholders such as schools and law enforcement, advocate for awareness, and provider education and resources for families.

Perhaps the most valuable resource, he said, is the Big Red Safety Box, available from the National Autism Association. This resource, sponsored by more than a half dozen autism advocacy organizations, includes three digital safety toolkits: one for caregivers, one for first responders, and one for teachers. Parents can therefore share the toolkits for first responders and teachers with those respective community members.

Pediatricians can also help families develop a Family Wandering Emergency Plan (FWEP), a template for which is in the Big Red Safety Box. Parents and community members should know the steps to take if someone wanders: Stay calm, call 911, search nearby water first and then implement the FWEP.

It’s first helpful to understand why these youth wander off. In the National Autism Association survey, the most common reasons were to escape an anxious situation, particularly for those with Asperger’s, or simply to run, explore, or go to a favorite place, particularly among those with autism or pervasive developmental disorder-not otherwise specified (PDD-NOS).

Researchers have found similar reasons: 43% of elopement situations occurred when children were trying to escape an anxious situation, 39% left while in a stressful environment, and 24% were in an environment with conflict, found one study (J Autism Dev Disord. 2019 Mar 5. doi: 10.1007/s10803-019-03961-x).

Sensory overload was also a trigger, with 38% of elopements occurring when it was too noisy, and 34% when it was a generally uncomfortable sensory experience. Just over a quarter (27%) of children left when they were understimulated or in a “boring” environment, Dr Lipkin reported. The remaining reason was goal-directed: 27% left to pursue a special interest, 18% sought a place where they enjoyed playing, and 11% were after their favorite food.
 

Prevention Strategies

Most data about effective strategies to prevent wandering comes from research that relies on parents, Dr Lipkin said. In general, environmental interventions tend to be the most effective, and medication tends to be the least effective.

One study on elopement prevention found that 96% of caregivers use at least some type of intervention, and the vast majority (83%) were using environmental interventions such as dead bolts (51%), latches (49%) and gates (36%). An equal proportion used behavioral services (83%), such as a behavioral psychologist (41%), social stories (40%) or an aide (39%). Just under a third used an ID bracelet or shoe tag (31%), and 19% used GPS trackers, according to Dr. Lipkin.

Although parents reported environmental interventions to be very effective, 68% said they were highly burdensome, though the median cost over 2 years was less than $1,000. The least expensive intervention was home behavioral specialists (when covered by insurance) and school aides, and the most expensive and burdensome – albeit highly effective – was a service animal.

Interventions with the least cost effectiveness included security cameras and GPS trackers, which only 15% of parents reported as being effective.

Although nearly half of parents reported their child had taken any psychiatric medication (48%), only 16% had taken medication explicitly to prevent wandering. Few reported the medication was very effective, however. Among the small number who did (less than 10), lorazepam, diazepam and atomoxetine appeared best.

Teaching children survival skills, as developmentally appropriate and possible, can also help. These include swimming lessons as well as learning how to interact in traffic, knowing their home address, and learning how to navigate around their neighborhood.

Dr. Lipkin no disclosures and used no external funding for this presentation.

AUSTIN, TEX. – Patients with peripheral neuropathy may benefit from genetic testing to determine of the cause of their neuropathy even if they do not have a family history of the condition, according to new research.

The same research identified more than 80 genetic variants in patients with neuropathy who lacked any other known genetic mutations, potentially representing not-yet-identified pathogenic mutations.

Sasa Zivkovic, MD, PhD, of the University of Pittsburgh Medical Center (UPMC), and associates shared a poster of their findings at the annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine.

The researchers conducted next-generation sequencing (NGS) on 85 adult patients with peripheral neuropathy at the UPMC Neuromuscular Clinic during May 2017–Feb. 2019. The targeted NGS panel included 70 genes. The patients, aged 60 years on average, were primarily from Allegheny County, Pa., and had neuropathy either suspected to be hereditary or of unknown etiology.

Among the 19% of patients (n = 16) who tested positive for a known pathogenic mutation, half had Charcot-Marie-Tooth disease type 1A (CMT1A). Two patients – 13% of those with pathogenic variants – had hereditary neuropathy with liability to pressure palsies, and two had CMT1X. The remaining four patients had CMT1B, CMT2B1, CMT2E, and hereditary sensory and autonomic neuropathy mutations.

Another 4% of the overall patient sample (n = 3) had likely pathogenic mutations in genes associated with CMT2S, CMT4C and CMT4F. A third of the patients (32%) tested negative for the full NGS panel, and, comprising the largest proportion of patients, 46% had variants of unknown significance.

“The high occurrence of variants of unknown significance has uncertain significance but some variations may represent unrecognized pathogenic mutations,” the authors noted.

They identified 81 of these variants, with the DST, PLEKHG5, and SPG11 genes most commonly affected, each found in six patients. Four patients had a variant in the next most commonly affected gene, SBF2. The following variants occurred in three people each: BICD2, NEFL3, PRX, SCN11A, SCN9A, SLC52A2, and WNK1.

Among the 73 patients who underwent electrodiagnostic testing, 44 had sporadic axonal neuropathy, 17 had sporadic demyelinating neuropathy, and 11 had mixed neuropathies; the 1 remaining patient was not accounted for. Positive genetic testing occurred in a third (32%) of those with familial neuropathy (n = 28) and in 12% of those with sporadic neuropathy (n = 57).

No external funding was noted, and the authors had no disclosures.

SOURCE: Zivkovic S et al. AANEM 2019. Abstract 160. Targeted genetic testing in the evaluation of neuropathy .

AUSTIN, TEX. – Patients with peripheral neuropathy may benefit from genetic testing to determine of the cause of their neuropathy even if they do not have a family history of the condition, according to new research.

The same research identified more than 80 genetic variants in patients with neuropathy who lacked any other known genetic mutations, potentially representing not-yet-identified pathogenic mutations.

Sasa Zivkovic, MD, PhD, of the University of Pittsburgh Medical Center (UPMC), and associates shared a poster of their findings at the annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine.

The researchers conducted next-generation sequencing (NGS) on 85 adult patients with peripheral neuropathy at the UPMC Neuromuscular Clinic during May 2017–Feb. 2019. The targeted NGS panel included 70 genes. The patients, aged 60 years on average, were primarily from Allegheny County, Pa., and had neuropathy either suspected to be hereditary or of unknown etiology.

Among the 19% of patients (n = 16) who tested positive for a known pathogenic mutation, half had Charcot-Marie-Tooth disease type 1A (CMT1A). Two patients – 13% of those with pathogenic variants – had hereditary neuropathy with liability to pressure palsies, and two had CMT1X. The remaining four patients had CMT1B, CMT2B1, CMT2E, and hereditary sensory and autonomic neuropathy mutations.

Another 4% of the overall patient sample (n = 3) had likely pathogenic mutations in genes associated with CMT2S, CMT4C and CMT4F. A third of the patients (32%) tested negative for the full NGS panel, and, comprising the largest proportion of patients, 46% had variants of unknown significance.

“The high occurrence of variants of unknown significance has uncertain significance but some variations may represent unrecognized pathogenic mutations,” the authors noted.

They identified 81 of these variants, with the DST, PLEKHG5, and SPG11 genes most commonly affected, each found in six patients. Four patients had a variant in the next most commonly affected gene, SBF2. The following variants occurred in three people each: BICD2, NEFL3, PRX, SCN11A, SCN9A, SLC52A2, and WNK1.

Among the 73 patients who underwent electrodiagnostic testing, 44 had sporadic axonal neuropathy, 17 had sporadic demyelinating neuropathy, and 11 had mixed neuropathies; the 1 remaining patient was not accounted for. Positive genetic testing occurred in a third (32%) of those with familial neuropathy (n = 28) and in 12% of those with sporadic neuropathy (n = 57).

No external funding was noted, and the authors had no disclosures.

SOURCE: Zivkovic S et al. AANEM 2019. Abstract 160. Targeted genetic testing in the evaluation of neuropathy .

AUSTIN, TEX. – Patients with peripheral neuropathy may benefit from genetic testing to determine of the cause of their neuropathy even if they do not have a family history of the condition, according to new research.

The same research identified more than 80 genetic variants in patients with neuropathy who lacked any other known genetic mutations, potentially representing not-yet-identified pathogenic mutations.

Sasa Zivkovic, MD, PhD, of the University of Pittsburgh Medical Center (UPMC), and associates shared a poster of their findings at the annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine.

The researchers conducted next-generation sequencing (NGS) on 85 adult patients with peripheral neuropathy at the UPMC Neuromuscular Clinic during May 2017–Feb. 2019. The targeted NGS panel included 70 genes. The patients, aged 60 years on average, were primarily from Allegheny County, Pa., and had neuropathy either suspected to be hereditary or of unknown etiology.

Among the 19% of patients (n = 16) who tested positive for a known pathogenic mutation, half had Charcot-Marie-Tooth disease type 1A (CMT1A). Two patients – 13% of those with pathogenic variants – had hereditary neuropathy with liability to pressure palsies, and two had CMT1X. The remaining four patients had CMT1B, CMT2B1, CMT2E, and hereditary sensory and autonomic neuropathy mutations.

Another 4% of the overall patient sample (n = 3) had likely pathogenic mutations in genes associated with CMT2S, CMT4C and CMT4F. A third of the patients (32%) tested negative for the full NGS panel, and, comprising the largest proportion of patients, 46% had variants of unknown significance.

“The high occurrence of variants of unknown significance has uncertain significance but some variations may represent unrecognized pathogenic mutations,” the authors noted.

They identified 81 of these variants, with the DST, PLEKHG5, and SPG11 genes most commonly affected, each found in six patients. Four patients had a variant in the next most commonly affected gene, SBF2. The following variants occurred in three people each: BICD2, NEFL3, PRX, SCN11A, SCN9A, SLC52A2, and WNK1.

Among the 73 patients who underwent electrodiagnostic testing, 44 had sporadic axonal neuropathy, 17 had sporadic demyelinating neuropathy, and 11 had mixed neuropathies; the 1 remaining patient was not accounted for. Positive genetic testing occurred in a third (32%) of those with familial neuropathy (n = 28) and in 12% of those with sporadic neuropathy (n = 57).

No external funding was noted, and the authors had no disclosures.

SOURCE: Zivkovic S et al. AANEM 2019. Abstract 160. Targeted genetic testing in the evaluation of neuropathy .

AUSTIN, TEX. – Dichlorphenamide continues to reduce attacks from primary periodic paralysis (PPP) through 1 year with mild or moderate paresthesia and cognition-related adverse events, according to new research.

“These adverse events rarely resulted in discontinuation from the study and were sometimes managed by dichlorphenamide dose reductions,” concluded Nicholas E. Johnson, MD, of Virginia Commonwealth University, Richmond, and colleagues. “Reduction in dose was frequently associated with resolution of these events, suggesting a potential intervention to hasten resolution.” Dr. Johnson presented the findings in an abstract at the annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine.

Dichlorphenamide (Keveyis) was approved by the Food and Drug Administration in 2015 for treating primary hyperkalemic and hypokalemic periodic paralysis and similar variants. The original hyperkalemic/hypokalemic PPP trial was a phase 3 randomized, double-blind, placebo-controlled trial that lasted 9 weeks and assessed the efficacy of dichlorphenamide in reducing PPP attacks and its adverse events. In the dichlorphenamide group, 47% experienced paresthesia, compared with 14% in the placebo group, and 19% experienced cognitive disorder, compared with 7% in the placebo.

In a 52-week open-label extension, participants who had been receiving the placebo switched to receiving 50 mg of dichlorphenamide twice daily. The intervention group continued with the dose they had been receiving when the 9-week double-blind phase ended. (During the initial intervention, they took either 50 mg twice daily or the dose they had at baseline for those taking it before the study began.)

The researchers then tracked rates of attacks and their severity over the next year – through week 61 after baseline – to compare these endpoints both within the intervention groups and between them.

Among the 63 predominantly white (84.1%) male (61.9%) adults who began the trial, 36 received dichlorphenamide and 27 received placebo. Just over two-thirds (68.3%) had hypokalemic PPP. Among the 47 patients (74.6%) who completed the open-label extension phase, 26 had been in the original dichlorphenamide group and 21 had been in the placebo group.

The median weekly attack rate in the dichlorphenamide group dropped from 1.75 at baseline to 0.06 at week 61 (median decrease 1.00, 93.8%; P less than .0001). In the placebo group that switched over to dichlorphenamide at week 9, the median weekly attack rate dropped from 3.00 at baseline to 0.25 at week 61 (median decrease 0.63, 75%; P = .01).

The median attack rate weighted for severity in the dichlorphenamide group dropped from 2.25 at baseline to 0.06 at week 61 (median decrease 2.25, 97.1%; P less than .0001). In the placebo group, it dropped from 5.88 to 0.50 (median decrease 1.69, 80.8%; P = .01).

No significant difference in median weekly attack rates and severity-weighted attack rates was found between the intervention groups through week 61.

Across all patients during the extension, 39.7% patients experienced at least one paresthesia adverse event, none of which were determined to be severe and resulting in one discontinuation.

A quarter of the participants (25.4%) experienced at least one cognition-related adverse event, and four patients (6.3%) discontinued because of these side effects. Most (14.3%) were mild with 7.9% reporting moderate and 3.2% reporting severe effects.

Dr. Johnson has received research support from or consulted with a variety of pharmaceutical companies including Strongbridge Biopharma, the manufacturer of the drug. Other authors consulted for several pharmaceutical companies, and one author is an employee of Strongbridge Biopharma.
 

SOURCE: Johnson NE et al. AANEM 2019. Abstract 102. Long-term efficacy and adverse event characterization of dichlorphenamide for the treatment of primary periodic paralysis.

AUSTIN, TEX. – Dichlorphenamide continues to reduce attacks from primary periodic paralysis (PPP) through 1 year with mild or moderate paresthesia and cognition-related adverse events, according to new research.

“These adverse events rarely resulted in discontinuation from the study and were sometimes managed by dichlorphenamide dose reductions,” concluded Nicholas E. Johnson, MD, of Virginia Commonwealth University, Richmond, and colleagues. “Reduction in dose was frequently associated with resolution of these events, suggesting a potential intervention to hasten resolution.” Dr. Johnson presented the findings in an abstract at the annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine.

Dichlorphenamide (Keveyis) was approved by the Food and Drug Administration in 2015 for treating primary hyperkalemic and hypokalemic periodic paralysis and similar variants. The original hyperkalemic/hypokalemic PPP trial was a phase 3 randomized, double-blind, placebo-controlled trial that lasted 9 weeks and assessed the efficacy of dichlorphenamide in reducing PPP attacks and its adverse events. In the dichlorphenamide group, 47% experienced paresthesia, compared with 14% in the placebo group, and 19% experienced cognitive disorder, compared with 7% in the placebo.

In a 52-week open-label extension, participants who had been receiving the placebo switched to receiving 50 mg of dichlorphenamide twice daily. The intervention group continued with the dose they had been receiving when the 9-week double-blind phase ended. (During the initial intervention, they took either 50 mg twice daily or the dose they had at baseline for those taking it before the study began.)

The researchers then tracked rates of attacks and their severity over the next year – through week 61 after baseline – to compare these endpoints both within the intervention groups and between them.

Among the 63 predominantly white (84.1%) male (61.9%) adults who began the trial, 36 received dichlorphenamide and 27 received placebo. Just over two-thirds (68.3%) had hypokalemic PPP. Among the 47 patients (74.6%) who completed the open-label extension phase, 26 had been in the original dichlorphenamide group and 21 had been in the placebo group.

The median weekly attack rate in the dichlorphenamide group dropped from 1.75 at baseline to 0.06 at week 61 (median decrease 1.00, 93.8%; P less than .0001). In the placebo group that switched over to dichlorphenamide at week 9, the median weekly attack rate dropped from 3.00 at baseline to 0.25 at week 61 (median decrease 0.63, 75%; P = .01).

The median attack rate weighted for severity in the dichlorphenamide group dropped from 2.25 at baseline to 0.06 at week 61 (median decrease 2.25, 97.1%; P less than .0001). In the placebo group, it dropped from 5.88 to 0.50 (median decrease 1.69, 80.8%; P = .01).

No significant difference in median weekly attack rates and severity-weighted attack rates was found between the intervention groups through week 61.

Across all patients during the extension, 39.7% patients experienced at least one paresthesia adverse event, none of which were determined to be severe and resulting in one discontinuation.

A quarter of the participants (25.4%) experienced at least one cognition-related adverse event, and four patients (6.3%) discontinued because of these side effects. Most (14.3%) were mild with 7.9% reporting moderate and 3.2% reporting severe effects.

Dr. Johnson has received research support from or consulted with a variety of pharmaceutical companies including Strongbridge Biopharma, the manufacturer of the drug. Other authors consulted for several pharmaceutical companies, and one author is an employee of Strongbridge Biopharma.
 

SOURCE: Johnson NE et al. AANEM 2019. Abstract 102. Long-term efficacy and adverse event characterization of dichlorphenamide for the treatment of primary periodic paralysis.

AUSTIN, TEX. – Dichlorphenamide continues to reduce attacks from primary periodic paralysis (PPP) through 1 year with mild or moderate paresthesia and cognition-related adverse events, according to new research.

“These adverse events rarely resulted in discontinuation from the study and were sometimes managed by dichlorphenamide dose reductions,” concluded Nicholas E. Johnson, MD, of Virginia Commonwealth University, Richmond, and colleagues. “Reduction in dose was frequently associated with resolution of these events, suggesting a potential intervention to hasten resolution.” Dr. Johnson presented the findings in an abstract at the annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine.

Dichlorphenamide (Keveyis) was approved by the Food and Drug Administration in 2015 for treating primary hyperkalemic and hypokalemic periodic paralysis and similar variants. The original hyperkalemic/hypokalemic PPP trial was a phase 3 randomized, double-blind, placebo-controlled trial that lasted 9 weeks and assessed the efficacy of dichlorphenamide in reducing PPP attacks and its adverse events. In the dichlorphenamide group, 47% experienced paresthesia, compared with 14% in the placebo group, and 19% experienced cognitive disorder, compared with 7% in the placebo.

In a 52-week open-label extension, participants who had been receiving the placebo switched to receiving 50 mg of dichlorphenamide twice daily. The intervention group continued with the dose they had been receiving when the 9-week double-blind phase ended. (During the initial intervention, they took either 50 mg twice daily or the dose they had at baseline for those taking it before the study began.)

The researchers then tracked rates of attacks and their severity over the next year – through week 61 after baseline – to compare these endpoints both within the intervention groups and between them.

Among the 63 predominantly white (84.1%) male (61.9%) adults who began the trial, 36 received dichlorphenamide and 27 received placebo. Just over two-thirds (68.3%) had hypokalemic PPP. Among the 47 patients (74.6%) who completed the open-label extension phase, 26 had been in the original dichlorphenamide group and 21 had been in the placebo group.

The median weekly attack rate in the dichlorphenamide group dropped from 1.75 at baseline to 0.06 at week 61 (median decrease 1.00, 93.8%; P less than .0001). In the placebo group that switched over to dichlorphenamide at week 9, the median weekly attack rate dropped from 3.00 at baseline to 0.25 at week 61 (median decrease 0.63, 75%; P = .01).

The median attack rate weighted for severity in the dichlorphenamide group dropped from 2.25 at baseline to 0.06 at week 61 (median decrease 2.25, 97.1%; P less than .0001). In the placebo group, it dropped from 5.88 to 0.50 (median decrease 1.69, 80.8%; P = .01).

No significant difference in median weekly attack rates and severity-weighted attack rates was found between the intervention groups through week 61.

Across all patients during the extension, 39.7% patients experienced at least one paresthesia adverse event, none of which were determined to be severe and resulting in one discontinuation.

A quarter of the participants (25.4%) experienced at least one cognition-related adverse event, and four patients (6.3%) discontinued because of these side effects. Most (14.3%) were mild with 7.9% reporting moderate and 3.2% reporting severe effects.

Dr. Johnson has received research support from or consulted with a variety of pharmaceutical companies including Strongbridge Biopharma, the manufacturer of the drug. Other authors consulted for several pharmaceutical companies, and one author is an employee of Strongbridge Biopharma.
 

SOURCE: Johnson NE et al. AANEM 2019. Abstract 102. Long-term efficacy and adverse event characterization of dichlorphenamide for the treatment of primary periodic paralysis.

AUSTIN, TEX. – The use of both repetitive stimulation (RS) and jitter analysis are important for accurate diagnosis of congenital myasthenic syndrome (CMS) suggests newly presented research.

“In case RS is negative, SFEMG [single fiber electromyography] alone is not very specific and cannot distinguish CMS from mitochondrial myopathies, even in the presence of impulse blocking,” Vitor Marques Caldas, MD, a neurologist at the Syrian Libanes Hospital in Brasilia, Brazil, and a PhD student at the University of São Paulo, told attendees at the annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine. “An isolated SFEMG test can lead to a misdiagnosis of myasthenia syndrome if not interpreted in the right clinical context.”

The researchers sought to understand the relative sensitivity and specificity of low-frequency RS versus jitter analysis using disposable concentric needle electrodes (CNE).

The study involved 69 patients, of whom 19 had mitochondrial myopathy, 18 had congenital myopathy, 18 had CMS, and 14 were asymptomatic controls. The control group all tested normal with both RS and jitter analysis.

The 18 participants with CMS, average age 24 years, received low-frequency RS in at least six different muscles: two distal muscles (abductor digiti minimi and tibialis anterior), two proximal muscles (deltoid and trapezius) and two facial muscles (nasalis and orbicularis oculi). They also underwent jitter analysis of their orbicularis oculi muscle under voluntary activation using CNE.

These patients had heterogeneous genetic profiles: 11 had the CHRNE gene mutation, 2 had the RAPSN gene mutation, 2 had the COLQ gene mutation, 2 had the DOK-7 gene mutation, and 1 had the COL13A1 mutation.

All but two patients with congenital CMS tested positive (88.9%) with RS: one female with CHRNE mutation and one male with RAPSN mutation. Using mean jitter, all but one patient tested positive (94.4%): a female with DOK-7 mutation who had tested abnormal on RS.

All patients with CMS tested positive with at least one of the two tests, but only 83.3% tested positive with both tests, resulting in a sensitivity of 83.3%, a specificity of 100%, and overall accuracy of 95.6% using both tests.

Among the 19 patients with mitochondrial myopathy, 5 had abnormal jitter analysis.

When the researchers looked only at participants with abnormal jitter analysis but normal RS, two of these were patients with CMS, but another seven had congenital or mitochondrial myopathies. Using abnormal jitter alone therefore resulted in a sensitivity of 100% but a specificity of only 86%, for overall 86.5% accuracy.

“It’s important to notice that if you have an abnormal jitter, we have to look at the clinical symptoms of the patients,” Dr. Marques Caldas said in an interview. “Jitter abnormalities are not enough to distinguish between myasthenic disorder and a myopathic disorder.”

The research used no external funding, and Dr. Marques Caldas had no disclosures.
 

SOURCE: Caldas VM et al. AANEM 2019. Unnumbered Abstract: Sensitivity of neurophysiologic tests regarding the neuromuscular junction in patients with congenital myasthenic syndromes.

AUSTIN, TEX. – The use of both repetitive stimulation (RS) and jitter analysis are important for accurate diagnosis of congenital myasthenic syndrome (CMS) suggests newly presented research.

“In case RS is negative, SFEMG [single fiber electromyography] alone is not very specific and cannot distinguish CMS from mitochondrial myopathies, even in the presence of impulse blocking,” Vitor Marques Caldas, MD, a neurologist at the Syrian Libanes Hospital in Brasilia, Brazil, and a PhD student at the University of São Paulo, told attendees at the annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine. “An isolated SFEMG test can lead to a misdiagnosis of myasthenia syndrome if not interpreted in the right clinical context.”

The researchers sought to understand the relative sensitivity and specificity of low-frequency RS versus jitter analysis using disposable concentric needle electrodes (CNE).

The study involved 69 patients, of whom 19 had mitochondrial myopathy, 18 had congenital myopathy, 18 had CMS, and 14 were asymptomatic controls. The control group all tested normal with both RS and jitter analysis.

The 18 participants with CMS, average age 24 years, received low-frequency RS in at least six different muscles: two distal muscles (abductor digiti minimi and tibialis anterior), two proximal muscles (deltoid and trapezius) and two facial muscles (nasalis and orbicularis oculi). They also underwent jitter analysis of their orbicularis oculi muscle under voluntary activation using CNE.

These patients had heterogeneous genetic profiles: 11 had the CHRNE gene mutation, 2 had the RAPSN gene mutation, 2 had the COLQ gene mutation, 2 had the DOK-7 gene mutation, and 1 had the COL13A1 mutation.

All but two patients with congenital CMS tested positive (88.9%) with RS: one female with CHRNE mutation and one male with RAPSN mutation. Using mean jitter, all but one patient tested positive (94.4%): a female with DOK-7 mutation who had tested abnormal on RS.

All patients with CMS tested positive with at least one of the two tests, but only 83.3% tested positive with both tests, resulting in a sensitivity of 83.3%, a specificity of 100%, and overall accuracy of 95.6% using both tests.

Among the 19 patients with mitochondrial myopathy, 5 had abnormal jitter analysis.

When the researchers looked only at participants with abnormal jitter analysis but normal RS, two of these were patients with CMS, but another seven had congenital or mitochondrial myopathies. Using abnormal jitter alone therefore resulted in a sensitivity of 100% but a specificity of only 86%, for overall 86.5% accuracy.

“It’s important to notice that if you have an abnormal jitter, we have to look at the clinical symptoms of the patients,” Dr. Marques Caldas said in an interview. “Jitter abnormalities are not enough to distinguish between myasthenic disorder and a myopathic disorder.”

The research used no external funding, and Dr. Marques Caldas had no disclosures.
 

SOURCE: Caldas VM et al. AANEM 2019. Unnumbered Abstract: Sensitivity of neurophysiologic tests regarding the neuromuscular junction in patients with congenital myasthenic syndromes.

AUSTIN, TEX. – The use of both repetitive stimulation (RS) and jitter analysis are important for accurate diagnosis of congenital myasthenic syndrome (CMS) suggests newly presented research.

“In case RS is negative, SFEMG [single fiber electromyography] alone is not very specific and cannot distinguish CMS from mitochondrial myopathies, even in the presence of impulse blocking,” Vitor Marques Caldas, MD, a neurologist at the Syrian Libanes Hospital in Brasilia, Brazil, and a PhD student at the University of São Paulo, told attendees at the annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine. “An isolated SFEMG test can lead to a misdiagnosis of myasthenia syndrome if not interpreted in the right clinical context.”

The researchers sought to understand the relative sensitivity and specificity of low-frequency RS versus jitter analysis using disposable concentric needle electrodes (CNE).

The study involved 69 patients, of whom 19 had mitochondrial myopathy, 18 had congenital myopathy, 18 had CMS, and 14 were asymptomatic controls. The control group all tested normal with both RS and jitter analysis.

The 18 participants with CMS, average age 24 years, received low-frequency RS in at least six different muscles: two distal muscles (abductor digiti minimi and tibialis anterior), two proximal muscles (deltoid and trapezius) and two facial muscles (nasalis and orbicularis oculi). They also underwent jitter analysis of their orbicularis oculi muscle under voluntary activation using CNE.

These patients had heterogeneous genetic profiles: 11 had the CHRNE gene mutation, 2 had the RAPSN gene mutation, 2 had the COLQ gene mutation, 2 had the DOK-7 gene mutation, and 1 had the COL13A1 mutation.

All but two patients with congenital CMS tested positive (88.9%) with RS: one female with CHRNE mutation and one male with RAPSN mutation. Using mean jitter, all but one patient tested positive (94.4%): a female with DOK-7 mutation who had tested abnormal on RS.

All patients with CMS tested positive with at least one of the two tests, but only 83.3% tested positive with both tests, resulting in a sensitivity of 83.3%, a specificity of 100%, and overall accuracy of 95.6% using both tests.

Among the 19 patients with mitochondrial myopathy, 5 had abnormal jitter analysis.

When the researchers looked only at participants with abnormal jitter analysis but normal RS, two of these were patients with CMS, but another seven had congenital or mitochondrial myopathies. Using abnormal jitter alone therefore resulted in a sensitivity of 100% but a specificity of only 86%, for overall 86.5% accuracy.

“It’s important to notice that if you have an abnormal jitter, we have to look at the clinical symptoms of the patients,” Dr. Marques Caldas said in an interview. “Jitter abnormalities are not enough to distinguish between myasthenic disorder and a myopathic disorder.”

The research used no external funding, and Dr. Marques Caldas had no disclosures.
 

SOURCE: Caldas VM et al. AANEM 2019. Unnumbered Abstract: Sensitivity of neurophysiologic tests regarding the neuromuscular junction in patients with congenital myasthenic syndromes.