User login
Rare neurological complication linked to Waldenstrom disease
Bilateral facial nerve palsy has been associated with underlying Waldenstrom disease in only one other known published case report, which was published in 2014. In a more recent case report published in the Journal of Clinical Neuroscience, Gabriel Torrealba-Acosta, MD, and colleagues in the department of neurology at Massachusetts General Hospital, Boston, described a second case involving a 67-year-old Hispanic man with a history of Waldenstrom disease who presented with subacute onset of bilateral facial weakness.
The patient, who had longstanding painful neuropathy, had presented to urgent care with a new-onset left facial nerve palsy, was then diagnosed with left Bell’s palsy, and began treatment with valacyclovir and prednisone.
The left-sided facial weakness gradually progressed to total paralysis of the left lower face and inability to close the left eye, and 2 weeks later, he developed right facial weakness that ran a similar course. The patient had a complicated clinical course that included symptomatic acute-on-chronic subdural hematoma, among other complications; eventually the patient’s symptoms stabilized and cranial neuropathies gradually improved, according to the report.
Bilateral facial nerve palsy is an extremely rare condition, occurring in just 0.3%-2% of all facial nerve palsy cases, according to the authors. By contrast, unilateral facial nerve palsy (or Bell’s palsy) is far more common, but it still occurs in only 25 patients per 100,000 population, they said.
Most cases of bilateral facial nerve palsy are caused by underlying Guillain-Barré syndrome, though some are congenital, related to trauma, or caused by etiologies that are metabolic, immunologic, or neoplastic in nature. While various types of neurological disturbances – from ischemic and hemorrhagic events to meningoencephalitis – have been documented to occur in up to a quarter of patients with Waldenstrom disease.
“Given the large differential that comprises the assessment of a bilateral facial nerve palsy, it warrants for an extensive work-up, and Waldenstrom’s macroglobulinemia should be sought as an additional possible etiology,” the authors wrote.
Dr. Torrealba-Acosta and coauthors reported having no financial disclosures.
SOURCE: Torrealba-Acosta G et al. J Clin Neurosci. 2017. doi: 10.1016/j.jocn.2017.10.081.
Bilateral facial nerve palsy has been associated with underlying Waldenstrom disease in only one other known published case report, which was published in 2014. In a more recent case report published in the Journal of Clinical Neuroscience, Gabriel Torrealba-Acosta, MD, and colleagues in the department of neurology at Massachusetts General Hospital, Boston, described a second case involving a 67-year-old Hispanic man with a history of Waldenstrom disease who presented with subacute onset of bilateral facial weakness.
The patient, who had longstanding painful neuropathy, had presented to urgent care with a new-onset left facial nerve palsy, was then diagnosed with left Bell’s palsy, and began treatment with valacyclovir and prednisone.
The left-sided facial weakness gradually progressed to total paralysis of the left lower face and inability to close the left eye, and 2 weeks later, he developed right facial weakness that ran a similar course. The patient had a complicated clinical course that included symptomatic acute-on-chronic subdural hematoma, among other complications; eventually the patient’s symptoms stabilized and cranial neuropathies gradually improved, according to the report.
Bilateral facial nerve palsy is an extremely rare condition, occurring in just 0.3%-2% of all facial nerve palsy cases, according to the authors. By contrast, unilateral facial nerve palsy (or Bell’s palsy) is far more common, but it still occurs in only 25 patients per 100,000 population, they said.
Most cases of bilateral facial nerve palsy are caused by underlying Guillain-Barré syndrome, though some are congenital, related to trauma, or caused by etiologies that are metabolic, immunologic, or neoplastic in nature. While various types of neurological disturbances – from ischemic and hemorrhagic events to meningoencephalitis – have been documented to occur in up to a quarter of patients with Waldenstrom disease.
“Given the large differential that comprises the assessment of a bilateral facial nerve palsy, it warrants for an extensive work-up, and Waldenstrom’s macroglobulinemia should be sought as an additional possible etiology,” the authors wrote.
Dr. Torrealba-Acosta and coauthors reported having no financial disclosures.
SOURCE: Torrealba-Acosta G et al. J Clin Neurosci. 2017. doi: 10.1016/j.jocn.2017.10.081.
Bilateral facial nerve palsy has been associated with underlying Waldenstrom disease in only one other known published case report, which was published in 2014. In a more recent case report published in the Journal of Clinical Neuroscience, Gabriel Torrealba-Acosta, MD, and colleagues in the department of neurology at Massachusetts General Hospital, Boston, described a second case involving a 67-year-old Hispanic man with a history of Waldenstrom disease who presented with subacute onset of bilateral facial weakness.
The patient, who had longstanding painful neuropathy, had presented to urgent care with a new-onset left facial nerve palsy, was then diagnosed with left Bell’s palsy, and began treatment with valacyclovir and prednisone.
The left-sided facial weakness gradually progressed to total paralysis of the left lower face and inability to close the left eye, and 2 weeks later, he developed right facial weakness that ran a similar course. The patient had a complicated clinical course that included symptomatic acute-on-chronic subdural hematoma, among other complications; eventually the patient’s symptoms stabilized and cranial neuropathies gradually improved, according to the report.
Bilateral facial nerve palsy is an extremely rare condition, occurring in just 0.3%-2% of all facial nerve palsy cases, according to the authors. By contrast, unilateral facial nerve palsy (or Bell’s palsy) is far more common, but it still occurs in only 25 patients per 100,000 population, they said.
Most cases of bilateral facial nerve palsy are caused by underlying Guillain-Barré syndrome, though some are congenital, related to trauma, or caused by etiologies that are metabolic, immunologic, or neoplastic in nature. While various types of neurological disturbances – from ischemic and hemorrhagic events to meningoencephalitis – have been documented to occur in up to a quarter of patients with Waldenstrom disease.
“Given the large differential that comprises the assessment of a bilateral facial nerve palsy, it warrants for an extensive work-up, and Waldenstrom’s macroglobulinemia should be sought as an additional possible etiology,” the authors wrote.
Dr. Torrealba-Acosta and coauthors reported having no financial disclosures.
SOURCE: Torrealba-Acosta G et al. J Clin Neurosci. 2017. doi: 10.1016/j.jocn.2017.10.081.
FROM THE JOURNAL OF CLINICAL NEUROSCIENCE
Edaravone: Costs versus benefits
On May 5, 2017, the Food and Drug Administration approved edaravone (Radicava) for the treatment of patients with amyotrophic lateral sclerosis (ALS). Developed by Mitsubishi Tanabe Pharma Corporation, edaravone is the first FDA-approved treatment for ALS since the approval of riluzole (Rilutek) in 1995. Edaravone was originally developed as an acute stroke treatment and then later studied in two separate trials in Japan to assess its efficacy in treating ALS.
Edaravone is administered intravenously and the standard dose of 60 mg takes about 1 hour to complete. The initial treatment cycle consists of once-daily dosing for 2 weeks, followed by a 2-week drug-free period. After the initial cycle, subsequent cycles consist of once-daily dosing for 10 days out of the next 2 weeks, followed by a 2-week drug-free period. The question of how long patients should take edaravone has not been resolved. The FDA did not define a limit to the duration of treatment. Some insurance companies have limited authorization to 6 months as that was the duration of treatment that showed benefit in the study. However, an open-label, 24-week extension of the second study showed that the change in ALSFRS-R was linear throughout the study. This suggests that the treatment benefit in patients with short duration of illness may continue for an additional 24 weeks. Thus, patients who have duration of illness of less than 2 years at presentation may benefit from 12 months of treatment.
The rigorous treatment schedule and IV administration of edaravone create additional concerns for ALS patients. Many patients will need to have a port placed. Patients with impaired mobility will need assistance with transportation to an infusion center. The time involved with taking all of these IV infusions will be considerable. Our experience at the Mayo Clinic reflects differing patient opinions. Some ALS patients with short duration of illness who clearly meet the criteria are not willing to commit to this form of therapy even if insurance will cover it. In contrast, some patients with advanced disease who do not meet the eligibility criteria have expressed the wish to try it.
To have access to edaravone in the United States, ALS patients must first complete an enrollment form and register with a Mitsubishi Tanabe subsidiary called Searchlight. Searchlight creates a Searchlight patient ID and conducts a benefit investigation to determine if the patient’s insurance will cover edaravone treatment. If the patient’s insurance approves edaravone, arrangements are made to ship the drug to the site or company that will perform the infusions. Insurance companies have taken different approaches to the approval of edaravone for ALS patients. Some insurers require that the patient meets the eligibility requirements of the Japanese study that showed benefit (duration of illness less than 2 years from symptom onset and forced vital capacity of at least 80% predicted). These strict criteria will exclude many patients. Other insurers have required only the diagnosis of ALS and the physician’s order. The cost of edaravone is estimated to be around $145,500 per year. The actual out-of-pocket cost to patients will vary depending on their specific insurance plans. In-home infusion of edaravone is another option patients can consider. Patients can pay the separate charges for in-home infusion if their insurance plans do not cover this.
The costs of edaravone are substantial. Beyond the expenses for the medication and infusion services, the patient faces the burden of committing time to frequent IV infusions and potential complications associated with having a port placed. Many ALS patients have decided against pursuing edaravone, suggesting that the perceived costs exceed the perceived benefits. Many ALS patients have started edaravone treatment with the belief that slowing of progression is worth the costs. It is too soon to know if those who have started edaravone will remain committed to the treatment for 6-12 months. Despite the differing approaches to edaravone treatment, it can be agreed upon that it is good to have a new treatment for ALS and that we must continue working to find therapies effective in substantially slowing or stopping the progression of ALS.
Ms. Chang is a research intern, and Dr. Ross is a professor of neurology and director of the ALS Clinic, at Mayo Clinic Arizona in Scottsdale. Dr. Ross reported serving as the Mayo Clinic Arizona site primary investigator for the ALS investigational drug NP001.
On May 5, 2017, the Food and Drug Administration approved edaravone (Radicava) for the treatment of patients with amyotrophic lateral sclerosis (ALS). Developed by Mitsubishi Tanabe Pharma Corporation, edaravone is the first FDA-approved treatment for ALS since the approval of riluzole (Rilutek) in 1995. Edaravone was originally developed as an acute stroke treatment and then later studied in two separate trials in Japan to assess its efficacy in treating ALS.
Edaravone is administered intravenously and the standard dose of 60 mg takes about 1 hour to complete. The initial treatment cycle consists of once-daily dosing for 2 weeks, followed by a 2-week drug-free period. After the initial cycle, subsequent cycles consist of once-daily dosing for 10 days out of the next 2 weeks, followed by a 2-week drug-free period. The question of how long patients should take edaravone has not been resolved. The FDA did not define a limit to the duration of treatment. Some insurance companies have limited authorization to 6 months as that was the duration of treatment that showed benefit in the study. However, an open-label, 24-week extension of the second study showed that the change in ALSFRS-R was linear throughout the study. This suggests that the treatment benefit in patients with short duration of illness may continue for an additional 24 weeks. Thus, patients who have duration of illness of less than 2 years at presentation may benefit from 12 months of treatment.
The rigorous treatment schedule and IV administration of edaravone create additional concerns for ALS patients. Many patients will need to have a port placed. Patients with impaired mobility will need assistance with transportation to an infusion center. The time involved with taking all of these IV infusions will be considerable. Our experience at the Mayo Clinic reflects differing patient opinions. Some ALS patients with short duration of illness who clearly meet the criteria are not willing to commit to this form of therapy even if insurance will cover it. In contrast, some patients with advanced disease who do not meet the eligibility criteria have expressed the wish to try it.
To have access to edaravone in the United States, ALS patients must first complete an enrollment form and register with a Mitsubishi Tanabe subsidiary called Searchlight. Searchlight creates a Searchlight patient ID and conducts a benefit investigation to determine if the patient’s insurance will cover edaravone treatment. If the patient’s insurance approves edaravone, arrangements are made to ship the drug to the site or company that will perform the infusions. Insurance companies have taken different approaches to the approval of edaravone for ALS patients. Some insurers require that the patient meets the eligibility requirements of the Japanese study that showed benefit (duration of illness less than 2 years from symptom onset and forced vital capacity of at least 80% predicted). These strict criteria will exclude many patients. Other insurers have required only the diagnosis of ALS and the physician’s order. The cost of edaravone is estimated to be around $145,500 per year. The actual out-of-pocket cost to patients will vary depending on their specific insurance plans. In-home infusion of edaravone is another option patients can consider. Patients can pay the separate charges for in-home infusion if their insurance plans do not cover this.
The costs of edaravone are substantial. Beyond the expenses for the medication and infusion services, the patient faces the burden of committing time to frequent IV infusions and potential complications associated with having a port placed. Many ALS patients have decided against pursuing edaravone, suggesting that the perceived costs exceed the perceived benefits. Many ALS patients have started edaravone treatment with the belief that slowing of progression is worth the costs. It is too soon to know if those who have started edaravone will remain committed to the treatment for 6-12 months. Despite the differing approaches to edaravone treatment, it can be agreed upon that it is good to have a new treatment for ALS and that we must continue working to find therapies effective in substantially slowing or stopping the progression of ALS.
Ms. Chang is a research intern, and Dr. Ross is a professor of neurology and director of the ALS Clinic, at Mayo Clinic Arizona in Scottsdale. Dr. Ross reported serving as the Mayo Clinic Arizona site primary investigator for the ALS investigational drug NP001.
On May 5, 2017, the Food and Drug Administration approved edaravone (Radicava) for the treatment of patients with amyotrophic lateral sclerosis (ALS). Developed by Mitsubishi Tanabe Pharma Corporation, edaravone is the first FDA-approved treatment for ALS since the approval of riluzole (Rilutek) in 1995. Edaravone was originally developed as an acute stroke treatment and then later studied in two separate trials in Japan to assess its efficacy in treating ALS.
Edaravone is administered intravenously and the standard dose of 60 mg takes about 1 hour to complete. The initial treatment cycle consists of once-daily dosing for 2 weeks, followed by a 2-week drug-free period. After the initial cycle, subsequent cycles consist of once-daily dosing for 10 days out of the next 2 weeks, followed by a 2-week drug-free period. The question of how long patients should take edaravone has not been resolved. The FDA did not define a limit to the duration of treatment. Some insurance companies have limited authorization to 6 months as that was the duration of treatment that showed benefit in the study. However, an open-label, 24-week extension of the second study showed that the change in ALSFRS-R was linear throughout the study. This suggests that the treatment benefit in patients with short duration of illness may continue for an additional 24 weeks. Thus, patients who have duration of illness of less than 2 years at presentation may benefit from 12 months of treatment.
The rigorous treatment schedule and IV administration of edaravone create additional concerns for ALS patients. Many patients will need to have a port placed. Patients with impaired mobility will need assistance with transportation to an infusion center. The time involved with taking all of these IV infusions will be considerable. Our experience at the Mayo Clinic reflects differing patient opinions. Some ALS patients with short duration of illness who clearly meet the criteria are not willing to commit to this form of therapy even if insurance will cover it. In contrast, some patients with advanced disease who do not meet the eligibility criteria have expressed the wish to try it.
To have access to edaravone in the United States, ALS patients must first complete an enrollment form and register with a Mitsubishi Tanabe subsidiary called Searchlight. Searchlight creates a Searchlight patient ID and conducts a benefit investigation to determine if the patient’s insurance will cover edaravone treatment. If the patient’s insurance approves edaravone, arrangements are made to ship the drug to the site or company that will perform the infusions. Insurance companies have taken different approaches to the approval of edaravone for ALS patients. Some insurers require that the patient meets the eligibility requirements of the Japanese study that showed benefit (duration of illness less than 2 years from symptom onset and forced vital capacity of at least 80% predicted). These strict criteria will exclude many patients. Other insurers have required only the diagnosis of ALS and the physician’s order. The cost of edaravone is estimated to be around $145,500 per year. The actual out-of-pocket cost to patients will vary depending on their specific insurance plans. In-home infusion of edaravone is another option patients can consider. Patients can pay the separate charges for in-home infusion if their insurance plans do not cover this.
The costs of edaravone are substantial. Beyond the expenses for the medication and infusion services, the patient faces the burden of committing time to frequent IV infusions and potential complications associated with having a port placed. Many ALS patients have decided against pursuing edaravone, suggesting that the perceived costs exceed the perceived benefits. Many ALS patients have started edaravone treatment with the belief that slowing of progression is worth the costs. It is too soon to know if those who have started edaravone will remain committed to the treatment for 6-12 months. Despite the differing approaches to edaravone treatment, it can be agreed upon that it is good to have a new treatment for ALS and that we must continue working to find therapies effective in substantially slowing or stopping the progression of ALS.
Ms. Chang is a research intern, and Dr. Ross is a professor of neurology and director of the ALS Clinic, at Mayo Clinic Arizona in Scottsdale. Dr. Ross reported serving as the Mayo Clinic Arizona site primary investigator for the ALS investigational drug NP001.
Further evidence supports link between Zika and GBS
Newly identified risk factors add to the growing evidence of a causal association between Zika virus and Guillain-Barré Syndrome (GBS), according to a case-control study.
In a study conducted in Puerto Rico, GBS diagnosis was confirmed in 39 of 47 (83%) patients with clinical suspicion of the syndrome from nine hospitals from April 2016 to December 2016. They were compared with 78 control patients to identify GBS risk factors. Three risk factors were identified, Emilio Dirlikov, PhD, of the division of scientific education and professional development for the Centers for Disease Control and Prevention in San Juan, Puerto Rico, and his coauthors said in a research letter to JAMA (2017;318[15]:1498).
“During Zika virus outbreaks, clinical suspicion should be elevated to improve GBS patient prognosis through prompt diagnosis and treatment,” Dr. Dirlikov and his coauthors wrote. This was a small study. “The pathophysiology of Zika virus infection and risk factors for developing GBS require further investigation. Clinical trials of the Zika virus vaccine should monitor for GBS,” they said.
The study was supported with a grant from the National Institutes of Health. Carlos A. Luciano, MD, also reported grant funding from the University of Puerto Rico Medical Sciences, San Juan. No other authors reported any financial disclosures.
Newly identified risk factors add to the growing evidence of a causal association between Zika virus and Guillain-Barré Syndrome (GBS), according to a case-control study.
In a study conducted in Puerto Rico, GBS diagnosis was confirmed in 39 of 47 (83%) patients with clinical suspicion of the syndrome from nine hospitals from April 2016 to December 2016. They were compared with 78 control patients to identify GBS risk factors. Three risk factors were identified, Emilio Dirlikov, PhD, of the division of scientific education and professional development for the Centers for Disease Control and Prevention in San Juan, Puerto Rico, and his coauthors said in a research letter to JAMA (2017;318[15]:1498).
“During Zika virus outbreaks, clinical suspicion should be elevated to improve GBS patient prognosis through prompt diagnosis and treatment,” Dr. Dirlikov and his coauthors wrote. This was a small study. “The pathophysiology of Zika virus infection and risk factors for developing GBS require further investigation. Clinical trials of the Zika virus vaccine should monitor for GBS,” they said.
The study was supported with a grant from the National Institutes of Health. Carlos A. Luciano, MD, also reported grant funding from the University of Puerto Rico Medical Sciences, San Juan. No other authors reported any financial disclosures.
Newly identified risk factors add to the growing evidence of a causal association between Zika virus and Guillain-Barré Syndrome (GBS), according to a case-control study.
In a study conducted in Puerto Rico, GBS diagnosis was confirmed in 39 of 47 (83%) patients with clinical suspicion of the syndrome from nine hospitals from April 2016 to December 2016. They were compared with 78 control patients to identify GBS risk factors. Three risk factors were identified, Emilio Dirlikov, PhD, of the division of scientific education and professional development for the Centers for Disease Control and Prevention in San Juan, Puerto Rico, and his coauthors said in a research letter to JAMA (2017;318[15]:1498).
“During Zika virus outbreaks, clinical suspicion should be elevated to improve GBS patient prognosis through prompt diagnosis and treatment,” Dr. Dirlikov and his coauthors wrote. This was a small study. “The pathophysiology of Zika virus infection and risk factors for developing GBS require further investigation. Clinical trials of the Zika virus vaccine should monitor for GBS,” they said.
The study was supported with a grant from the National Institutes of Health. Carlos A. Luciano, MD, also reported grant funding from the University of Puerto Rico Medical Sciences, San Juan. No other authors reported any financial disclosures.
FROM JAMA
Key clinical point:
Major finding: Case patients saw higher rates of acute illness within the previous 2 months (82%), acute Zika virus infection (23%), and any laboratory evidence of Zika virus infection (69%), compared with controls.
Data source: A case-control study of 39 patients with GBS and 78 controls.
Disclosures: The study was supported with a grant from the National Institutes of Health. Carlos A. Luciano, MD, also reported grant funding from the University of Puerto Rico Medical Sciences, San Juan. No other authors reported any financial disclosures.
Plenary sessions at ANA 2017 cover wide spectrum of neurologic topics
The six plenary sessions of the annual meeting of the American Neurological Association, taking place Oct. 15-17 in San Diego, promise to cover a broad range of research areas, including neuronal circuits and behavior, global neurology, precision medicine, antisense oligonucleotide therapies, and molecular imaging.
The morning of Oct. 15 starts off with the plenary session, “Linking Circuits to Behavior: Promise & Peril,” which seeks to impart how technologies such as optogenetics enable manipulation of discrete neural populations but require careful consideration of the methods for interpreting the resulting data in order to translate it to human functional neuroimaging for potential therapeutic use.
Later, in the afternoon of Oct. 15, the traditional Derek Denny-Brown Young Neurological Scholar Symposium will showcase the presentations from the two clinical science winners and one basic science winner of the Derek Denny-Brown Young Neurological Scholar Awards, as well as the 2017 Distinguished Neurology Teacher Award, the 2017 Grass Foundation ANA Award in Neuroscience, and the 2017 Wolfe Neuropathy Research Prize. The Derek Denny-Brown Young Neurological Scholar Award recognizes neurologists and neuroscientists in the first 10 years of their career at the assistant/associate faculty (equivalent) level who have made outstanding basic and clinical scientific advances toward the prevention, diagnosis, treatment, and cure of neurologic diseases. This year, award winner Keven N. Sheth, MD, of Yale University, New Haven, Conn., will present on “Instructive, Pragmatic, and Successful Trials in Acute Brain Injury: Making Intracerebral Hemorrhage the LEAST Devastating Form of Stroke”; Leslie E. Skolarus, MD, of the University of Michigan, Ann Arbor, will present on “Reducing the Burden of Stroke in a Disadvantaged Community”; and Conrad Chris Weihl, MD, PhD, of Washington University in St. Louis will present on “Connecting Protein Quality Control Pathways in Skeletal Muscle and Muscle Disease.” The 2017 Distinguished Neurology Teacher Award goes to Zachary Nathaniel London, MD, of the University of Michigan, Ann Arbor. The winner of this year’s Grass Foundation ANA Award in Neuroscience, which goes to an outstanding young physician-scientist conducting research in basic or clinical neuroscience, is Clotilde Lagier-Tourenne, MD, PhD, of Massachusetts General Hospital, Boston, who will discuss “Modeling C9ORF72 Disease: A Crucial Step for Therapeutic Development in ALS and Frontotemporal Dementia.” The symposium’s final presentation will have Stefanie Geisler, MD, of Washington University in St. Louis, talk about “Targeting a Core Axonal Degeneration Program to Treat Vincristine and Bortezomib-Induced Axonal Degeneration.” Dr. Geisler won the Wolfe Neuropathy Research Prize, which honors outstanding investigators who identify a new cause or treatment of axonal peripheral neuropathy.
The morning plenary session on Oct. 16 will focus on translational neuroscience efforts that are paying off with discoveries and insights into neurologic disorders that have higher prevalence or greater relevance to low- and middle-income countries. Presentations on these efforts will include discussion of the causation and prevention of Konzo, a distinct upper–motor neuron disease associated with cassava cyanogenic poisoning in sub-Saharan Africa; a case-control study on the impact of multiple mycotoxins on the development of Nodding syndrome in northern Uganda; efforts to address neurologic manifestations of sexually transmitted virus infections in Peru; a longitudinal cohort study of neurologic sequelae in Ebola virus disease survivors in Liberia; efforts to protect against cerebral malaria; the epidemiology of peripheral neuropathy in urban and rural Bangladeshi type 2 diabetes patients; and the use of smartphones and teleconsultations to improve care for people with epilepsy in low- and middle-income countries.
“Precision Medicine in Neurologic Disease” is the theme of four presentations in the afternoon plenary session on Oct. 16. Huda Y. Zoghbi, MD, of Baylor University, and Texas Children’s Hospital in Houston will talk about how her work in animal models of disease has enabled new insights into the effect that certain regulator proteins have on levels of disease-driving proteins such as tau and alpha-synuclein in neurodegenerative diseases. Amy Wagers, PhD, of Harvard Medical School, Boston, will describe her lab’s use of the gene-editing potential of the CRISPR-Cas9 system to fix frame-disrupting mutations in the Duchenne muscular dystrophy gene, DMD, which encodes dystrophin, and produce functional dystrophin expression in muscle stem cells in a mouse model of the disease, which partially recovered functional deficiencies of dystrophic muscle. Donald Berry, PhD, of the University of Texas, M.D. Anderson Cancer Center in Houston plans to discuss the importance of adaptive platform trials – which match therapies to patients – from oncology to neurologic therapy trials and the lessons learned from two major ongoing oncology treatment trials. Cristina Sampaio, MD, PhD, of the CHDI Foundation, aims to inform attendees of the power of prognostic and predictive biomarker-guided trials in neurology to improve the likelihood of success of drug development. Three high-scoring abstracts in the field of precision medicine also will be presented.
The final day of the meeting brings a morning plenary session on “Antisense Oligonucleotide Treatment of Genetic Neurological Diseases” that will focus on the use of antisense oligonucleotides (ASOs) to silence specific genes or alter their pre-mRNA splicing in Duchenne muscular dystrophy, spinal muscular atrophy, Huntington’s disease, amyotrophic lateral sclerosis, and tauopathies. Additional presentations will focus on abstracts about blood and salivary biomarkers in Huntington’s disease and the early efficacy and safety results of an ASO in patients with hereditary transthyretin amyloidosis with polyneuropathy.
The expanding use and development of methods to assess brain pathology in vivo sets the scene for the meeting’s final plenary session, “Molecular Imaging in Neurologic Disease” in the afternoon of Oct. 17. The use of positron emission tomography and single-photon emission computed tomography (SPECT) tracers for glucose metabolism, the dopamine system, amyloid-beta, tau, synaptic markers, and activated microglia has grown substantially to investigate disease mechanisms, develop new therapeutics, and provide diagnostic and prognostic clinical care. Reisa Sperling, MD, of Harvard Medical School, Boston, will provide an overview of the direction of PET ligand use and development in diagnosing early Alzheimer’s disease. Nicolaas I. Bohnen, MD, PhD, of the University of Michigan, Ann Arbor, will describe a hypothesis for how hypercholinergic activity in the brain of Parkinson’s disease patients may for a time compensate for the loss of striatal dopamine and influence the appearance of a tremor-predominant motor phenotype in patients. Richard E. Carson, PhD, of Yale University will focus on the development of PET ligands to monitor synaptic density loss in neuropsychiatric disorders. Noninvasive imaging has also begun to influence research in the detection of neuroinflammation in a wide variety of conditions, with most research focusing on tracers for activated microglia and astrocytes, according to speaker Martin Pomper, MD, PhD, of Johns Hopkins University, Baltimore. The session will conclude with three molecular imaging abstract presentations.
The six plenary sessions of the annual meeting of the American Neurological Association, taking place Oct. 15-17 in San Diego, promise to cover a broad range of research areas, including neuronal circuits and behavior, global neurology, precision medicine, antisense oligonucleotide therapies, and molecular imaging.
The morning of Oct. 15 starts off with the plenary session, “Linking Circuits to Behavior: Promise & Peril,” which seeks to impart how technologies such as optogenetics enable manipulation of discrete neural populations but require careful consideration of the methods for interpreting the resulting data in order to translate it to human functional neuroimaging for potential therapeutic use.
Later, in the afternoon of Oct. 15, the traditional Derek Denny-Brown Young Neurological Scholar Symposium will showcase the presentations from the two clinical science winners and one basic science winner of the Derek Denny-Brown Young Neurological Scholar Awards, as well as the 2017 Distinguished Neurology Teacher Award, the 2017 Grass Foundation ANA Award in Neuroscience, and the 2017 Wolfe Neuropathy Research Prize. The Derek Denny-Brown Young Neurological Scholar Award recognizes neurologists and neuroscientists in the first 10 years of their career at the assistant/associate faculty (equivalent) level who have made outstanding basic and clinical scientific advances toward the prevention, diagnosis, treatment, and cure of neurologic diseases. This year, award winner Keven N. Sheth, MD, of Yale University, New Haven, Conn., will present on “Instructive, Pragmatic, and Successful Trials in Acute Brain Injury: Making Intracerebral Hemorrhage the LEAST Devastating Form of Stroke”; Leslie E. Skolarus, MD, of the University of Michigan, Ann Arbor, will present on “Reducing the Burden of Stroke in a Disadvantaged Community”; and Conrad Chris Weihl, MD, PhD, of Washington University in St. Louis will present on “Connecting Protein Quality Control Pathways in Skeletal Muscle and Muscle Disease.” The 2017 Distinguished Neurology Teacher Award goes to Zachary Nathaniel London, MD, of the University of Michigan, Ann Arbor. The winner of this year’s Grass Foundation ANA Award in Neuroscience, which goes to an outstanding young physician-scientist conducting research in basic or clinical neuroscience, is Clotilde Lagier-Tourenne, MD, PhD, of Massachusetts General Hospital, Boston, who will discuss “Modeling C9ORF72 Disease: A Crucial Step for Therapeutic Development in ALS and Frontotemporal Dementia.” The symposium’s final presentation will have Stefanie Geisler, MD, of Washington University in St. Louis, talk about “Targeting a Core Axonal Degeneration Program to Treat Vincristine and Bortezomib-Induced Axonal Degeneration.” Dr. Geisler won the Wolfe Neuropathy Research Prize, which honors outstanding investigators who identify a new cause or treatment of axonal peripheral neuropathy.
The morning plenary session on Oct. 16 will focus on translational neuroscience efforts that are paying off with discoveries and insights into neurologic disorders that have higher prevalence or greater relevance to low- and middle-income countries. Presentations on these efforts will include discussion of the causation and prevention of Konzo, a distinct upper–motor neuron disease associated with cassava cyanogenic poisoning in sub-Saharan Africa; a case-control study on the impact of multiple mycotoxins on the development of Nodding syndrome in northern Uganda; efforts to address neurologic manifestations of sexually transmitted virus infections in Peru; a longitudinal cohort study of neurologic sequelae in Ebola virus disease survivors in Liberia; efforts to protect against cerebral malaria; the epidemiology of peripheral neuropathy in urban and rural Bangladeshi type 2 diabetes patients; and the use of smartphones and teleconsultations to improve care for people with epilepsy in low- and middle-income countries.
“Precision Medicine in Neurologic Disease” is the theme of four presentations in the afternoon plenary session on Oct. 16. Huda Y. Zoghbi, MD, of Baylor University, and Texas Children’s Hospital in Houston will talk about how her work in animal models of disease has enabled new insights into the effect that certain regulator proteins have on levels of disease-driving proteins such as tau and alpha-synuclein in neurodegenerative diseases. Amy Wagers, PhD, of Harvard Medical School, Boston, will describe her lab’s use of the gene-editing potential of the CRISPR-Cas9 system to fix frame-disrupting mutations in the Duchenne muscular dystrophy gene, DMD, which encodes dystrophin, and produce functional dystrophin expression in muscle stem cells in a mouse model of the disease, which partially recovered functional deficiencies of dystrophic muscle. Donald Berry, PhD, of the University of Texas, M.D. Anderson Cancer Center in Houston plans to discuss the importance of adaptive platform trials – which match therapies to patients – from oncology to neurologic therapy trials and the lessons learned from two major ongoing oncology treatment trials. Cristina Sampaio, MD, PhD, of the CHDI Foundation, aims to inform attendees of the power of prognostic and predictive biomarker-guided trials in neurology to improve the likelihood of success of drug development. Three high-scoring abstracts in the field of precision medicine also will be presented.
The final day of the meeting brings a morning plenary session on “Antisense Oligonucleotide Treatment of Genetic Neurological Diseases” that will focus on the use of antisense oligonucleotides (ASOs) to silence specific genes or alter their pre-mRNA splicing in Duchenne muscular dystrophy, spinal muscular atrophy, Huntington’s disease, amyotrophic lateral sclerosis, and tauopathies. Additional presentations will focus on abstracts about blood and salivary biomarkers in Huntington’s disease and the early efficacy and safety results of an ASO in patients with hereditary transthyretin amyloidosis with polyneuropathy.
The expanding use and development of methods to assess brain pathology in vivo sets the scene for the meeting’s final plenary session, “Molecular Imaging in Neurologic Disease” in the afternoon of Oct. 17. The use of positron emission tomography and single-photon emission computed tomography (SPECT) tracers for glucose metabolism, the dopamine system, amyloid-beta, tau, synaptic markers, and activated microglia has grown substantially to investigate disease mechanisms, develop new therapeutics, and provide diagnostic and prognostic clinical care. Reisa Sperling, MD, of Harvard Medical School, Boston, will provide an overview of the direction of PET ligand use and development in diagnosing early Alzheimer’s disease. Nicolaas I. Bohnen, MD, PhD, of the University of Michigan, Ann Arbor, will describe a hypothesis for how hypercholinergic activity in the brain of Parkinson’s disease patients may for a time compensate for the loss of striatal dopamine and influence the appearance of a tremor-predominant motor phenotype in patients. Richard E. Carson, PhD, of Yale University will focus on the development of PET ligands to monitor synaptic density loss in neuropsychiatric disorders. Noninvasive imaging has also begun to influence research in the detection of neuroinflammation in a wide variety of conditions, with most research focusing on tracers for activated microglia and astrocytes, according to speaker Martin Pomper, MD, PhD, of Johns Hopkins University, Baltimore. The session will conclude with three molecular imaging abstract presentations.
The six plenary sessions of the annual meeting of the American Neurological Association, taking place Oct. 15-17 in San Diego, promise to cover a broad range of research areas, including neuronal circuits and behavior, global neurology, precision medicine, antisense oligonucleotide therapies, and molecular imaging.
The morning of Oct. 15 starts off with the plenary session, “Linking Circuits to Behavior: Promise & Peril,” which seeks to impart how technologies such as optogenetics enable manipulation of discrete neural populations but require careful consideration of the methods for interpreting the resulting data in order to translate it to human functional neuroimaging for potential therapeutic use.
Later, in the afternoon of Oct. 15, the traditional Derek Denny-Brown Young Neurological Scholar Symposium will showcase the presentations from the two clinical science winners and one basic science winner of the Derek Denny-Brown Young Neurological Scholar Awards, as well as the 2017 Distinguished Neurology Teacher Award, the 2017 Grass Foundation ANA Award in Neuroscience, and the 2017 Wolfe Neuropathy Research Prize. The Derek Denny-Brown Young Neurological Scholar Award recognizes neurologists and neuroscientists in the first 10 years of their career at the assistant/associate faculty (equivalent) level who have made outstanding basic and clinical scientific advances toward the prevention, diagnosis, treatment, and cure of neurologic diseases. This year, award winner Keven N. Sheth, MD, of Yale University, New Haven, Conn., will present on “Instructive, Pragmatic, and Successful Trials in Acute Brain Injury: Making Intracerebral Hemorrhage the LEAST Devastating Form of Stroke”; Leslie E. Skolarus, MD, of the University of Michigan, Ann Arbor, will present on “Reducing the Burden of Stroke in a Disadvantaged Community”; and Conrad Chris Weihl, MD, PhD, of Washington University in St. Louis will present on “Connecting Protein Quality Control Pathways in Skeletal Muscle and Muscle Disease.” The 2017 Distinguished Neurology Teacher Award goes to Zachary Nathaniel London, MD, of the University of Michigan, Ann Arbor. The winner of this year’s Grass Foundation ANA Award in Neuroscience, which goes to an outstanding young physician-scientist conducting research in basic or clinical neuroscience, is Clotilde Lagier-Tourenne, MD, PhD, of Massachusetts General Hospital, Boston, who will discuss “Modeling C9ORF72 Disease: A Crucial Step for Therapeutic Development in ALS and Frontotemporal Dementia.” The symposium’s final presentation will have Stefanie Geisler, MD, of Washington University in St. Louis, talk about “Targeting a Core Axonal Degeneration Program to Treat Vincristine and Bortezomib-Induced Axonal Degeneration.” Dr. Geisler won the Wolfe Neuropathy Research Prize, which honors outstanding investigators who identify a new cause or treatment of axonal peripheral neuropathy.
The morning plenary session on Oct. 16 will focus on translational neuroscience efforts that are paying off with discoveries and insights into neurologic disorders that have higher prevalence or greater relevance to low- and middle-income countries. Presentations on these efforts will include discussion of the causation and prevention of Konzo, a distinct upper–motor neuron disease associated with cassava cyanogenic poisoning in sub-Saharan Africa; a case-control study on the impact of multiple mycotoxins on the development of Nodding syndrome in northern Uganda; efforts to address neurologic manifestations of sexually transmitted virus infections in Peru; a longitudinal cohort study of neurologic sequelae in Ebola virus disease survivors in Liberia; efforts to protect against cerebral malaria; the epidemiology of peripheral neuropathy in urban and rural Bangladeshi type 2 diabetes patients; and the use of smartphones and teleconsultations to improve care for people with epilepsy in low- and middle-income countries.
“Precision Medicine in Neurologic Disease” is the theme of four presentations in the afternoon plenary session on Oct. 16. Huda Y. Zoghbi, MD, of Baylor University, and Texas Children’s Hospital in Houston will talk about how her work in animal models of disease has enabled new insights into the effect that certain regulator proteins have on levels of disease-driving proteins such as tau and alpha-synuclein in neurodegenerative diseases. Amy Wagers, PhD, of Harvard Medical School, Boston, will describe her lab’s use of the gene-editing potential of the CRISPR-Cas9 system to fix frame-disrupting mutations in the Duchenne muscular dystrophy gene, DMD, which encodes dystrophin, and produce functional dystrophin expression in muscle stem cells in a mouse model of the disease, which partially recovered functional deficiencies of dystrophic muscle. Donald Berry, PhD, of the University of Texas, M.D. Anderson Cancer Center in Houston plans to discuss the importance of adaptive platform trials – which match therapies to patients – from oncology to neurologic therapy trials and the lessons learned from two major ongoing oncology treatment trials. Cristina Sampaio, MD, PhD, of the CHDI Foundation, aims to inform attendees of the power of prognostic and predictive biomarker-guided trials in neurology to improve the likelihood of success of drug development. Three high-scoring abstracts in the field of precision medicine also will be presented.
The final day of the meeting brings a morning plenary session on “Antisense Oligonucleotide Treatment of Genetic Neurological Diseases” that will focus on the use of antisense oligonucleotides (ASOs) to silence specific genes or alter their pre-mRNA splicing in Duchenne muscular dystrophy, spinal muscular atrophy, Huntington’s disease, amyotrophic lateral sclerosis, and tauopathies. Additional presentations will focus on abstracts about blood and salivary biomarkers in Huntington’s disease and the early efficacy and safety results of an ASO in patients with hereditary transthyretin amyloidosis with polyneuropathy.
The expanding use and development of methods to assess brain pathology in vivo sets the scene for the meeting’s final plenary session, “Molecular Imaging in Neurologic Disease” in the afternoon of Oct. 17. The use of positron emission tomography and single-photon emission computed tomography (SPECT) tracers for glucose metabolism, the dopamine system, amyloid-beta, tau, synaptic markers, and activated microglia has grown substantially to investigate disease mechanisms, develop new therapeutics, and provide diagnostic and prognostic clinical care. Reisa Sperling, MD, of Harvard Medical School, Boston, will provide an overview of the direction of PET ligand use and development in diagnosing early Alzheimer’s disease. Nicolaas I. Bohnen, MD, PhD, of the University of Michigan, Ann Arbor, will describe a hypothesis for how hypercholinergic activity in the brain of Parkinson’s disease patients may for a time compensate for the loss of striatal dopamine and influence the appearance of a tremor-predominant motor phenotype in patients. Richard E. Carson, PhD, of Yale University will focus on the development of PET ligands to monitor synaptic density loss in neuropsychiatric disorders. Noninvasive imaging has also begun to influence research in the detection of neuroinflammation in a wide variety of conditions, with most research focusing on tracers for activated microglia and astrocytes, according to speaker Martin Pomper, MD, PhD, of Johns Hopkins University, Baltimore. The session will conclude with three molecular imaging abstract presentations.
Carpal tunnel syndrome may flag cardiac amyloidosis in elderly
DALLAS – Older patients with carpal tunnel syndrome that requires release surgery appear to have a relatively high prevalence of amyloidosis that, in some, involves their heart, suggesting that routine screening for amyloidosis is warranted in elderly patients undergoing the surgery.
Routine Congo red staining of a tenosynovial biopsy taken at the time of carpal tunnel release surgery in a single-center experience with 96 patients showed that 10 (10%) were positive for amyloidosis, Mazen Hanna, MD, said at the annual scientific meeting of the Heart Failure Society of America.
Clinicians “should be aware of the association between carpal tunnel syndrome [CTS] and amyloidosis.” When a 60-year old shows up with bilateral CTS without a clear cause, it’s reasonable to suspect amyloidosis, he suggested.
The prospective study run by Dr. Hanna and his associates included men at least 50 years old and women at least 60 years old who underwent CTS release surgery at the Cleveland Clinic during May 2016–June 2017. Enrollment excluded patients with known amyloidosis or rheumatoid arthritis. The patients averaged 68 years of age, 51% were men, and 85% had bilateral CTS that required surgery. The surgeons removed a tenosynovial biopsy at the time of surgery from each of the 96 patients, a “low-risk procedure,” Dr. Hanna said.
The 10 patients with positive staining for amyloid underwent a work-up that included a comprehensive physical examination, a series of blood tests for cardiac biomarkers, an ECG, echocardiography including assessment of cardiac strain, and a technetium-99m pyrophosphate scan. This identified two patients with cardiac involvement. The examinations identified one case by the echocardiographic strain findings and the second case by the technetium pyrophosphate scan. Seven of the 10 patients with amyloid had a history of prior carpal tunnel release surgery.
The researchers also used mass spectroscopy to identify the amyloid type. Seven patients had the transthyretin subtype, including one patient with cardiac involvement; two patients had light chain amyloidosis, including the second patient with cardiac involvement. The tenth patient had inconclusive results but the researchers presumed the amyloid was of the transthyretin type, Dr. Hanna said.
The eight patients identified with amyloid but no cardiac involvement at baseline will continue to receive annual work ups to see whether their hearts become affected over time. The protocol delays a repeat technetium pyrophosphate scan until the 4th year following study entry.
The potential usefulness of early identification and treatment of cardiac amyloidosis received support in results from another study reported at the meeting. Researchers from Columbia University Medical Center, New York, and New York Presbyterian Hospital reported their retrospective, nonrandomized experience with 126 patients who had been diagnosed with transthyretin cardiac amyloidosis. Thirty of these patients had received treatment with a transthyretin-stabilizing drug, either the investigational agent tafamidis or diflunisal, while the other 96 patients received no stabilizing treatment. During a median follow-up of 2 years, patients treated with a stabilizing agent had a statistically significant 68% reduced rate of either death or orthotopic heart transplant, compared with the untreated patients in a multivariate analysis that controlled for various baseline differences between the treated and untreated patients.
[email protected]
On Twitter @mitchelzoler
DALLAS – Older patients with carpal tunnel syndrome that requires release surgery appear to have a relatively high prevalence of amyloidosis that, in some, involves their heart, suggesting that routine screening for amyloidosis is warranted in elderly patients undergoing the surgery.
Routine Congo red staining of a tenosynovial biopsy taken at the time of carpal tunnel release surgery in a single-center experience with 96 patients showed that 10 (10%) were positive for amyloidosis, Mazen Hanna, MD, said at the annual scientific meeting of the Heart Failure Society of America.
Clinicians “should be aware of the association between carpal tunnel syndrome [CTS] and amyloidosis.” When a 60-year old shows up with bilateral CTS without a clear cause, it’s reasonable to suspect amyloidosis, he suggested.
The prospective study run by Dr. Hanna and his associates included men at least 50 years old and women at least 60 years old who underwent CTS release surgery at the Cleveland Clinic during May 2016–June 2017. Enrollment excluded patients with known amyloidosis or rheumatoid arthritis. The patients averaged 68 years of age, 51% were men, and 85% had bilateral CTS that required surgery. The surgeons removed a tenosynovial biopsy at the time of surgery from each of the 96 patients, a “low-risk procedure,” Dr. Hanna said.
The 10 patients with positive staining for amyloid underwent a work-up that included a comprehensive physical examination, a series of blood tests for cardiac biomarkers, an ECG, echocardiography including assessment of cardiac strain, and a technetium-99m pyrophosphate scan. This identified two patients with cardiac involvement. The examinations identified one case by the echocardiographic strain findings and the second case by the technetium pyrophosphate scan. Seven of the 10 patients with amyloid had a history of prior carpal tunnel release surgery.
The researchers also used mass spectroscopy to identify the amyloid type. Seven patients had the transthyretin subtype, including one patient with cardiac involvement; two patients had light chain amyloidosis, including the second patient with cardiac involvement. The tenth patient had inconclusive results but the researchers presumed the amyloid was of the transthyretin type, Dr. Hanna said.
The eight patients identified with amyloid but no cardiac involvement at baseline will continue to receive annual work ups to see whether their hearts become affected over time. The protocol delays a repeat technetium pyrophosphate scan until the 4th year following study entry.
The potential usefulness of early identification and treatment of cardiac amyloidosis received support in results from another study reported at the meeting. Researchers from Columbia University Medical Center, New York, and New York Presbyterian Hospital reported their retrospective, nonrandomized experience with 126 patients who had been diagnosed with transthyretin cardiac amyloidosis. Thirty of these patients had received treatment with a transthyretin-stabilizing drug, either the investigational agent tafamidis or diflunisal, while the other 96 patients received no stabilizing treatment. During a median follow-up of 2 years, patients treated with a stabilizing agent had a statistically significant 68% reduced rate of either death or orthotopic heart transplant, compared with the untreated patients in a multivariate analysis that controlled for various baseline differences between the treated and untreated patients.
[email protected]
On Twitter @mitchelzoler
DALLAS – Older patients with carpal tunnel syndrome that requires release surgery appear to have a relatively high prevalence of amyloidosis that, in some, involves their heart, suggesting that routine screening for amyloidosis is warranted in elderly patients undergoing the surgery.
Routine Congo red staining of a tenosynovial biopsy taken at the time of carpal tunnel release surgery in a single-center experience with 96 patients showed that 10 (10%) were positive for amyloidosis, Mazen Hanna, MD, said at the annual scientific meeting of the Heart Failure Society of America.
Clinicians “should be aware of the association between carpal tunnel syndrome [CTS] and amyloidosis.” When a 60-year old shows up with bilateral CTS without a clear cause, it’s reasonable to suspect amyloidosis, he suggested.
The prospective study run by Dr. Hanna and his associates included men at least 50 years old and women at least 60 years old who underwent CTS release surgery at the Cleveland Clinic during May 2016–June 2017. Enrollment excluded patients with known amyloidosis or rheumatoid arthritis. The patients averaged 68 years of age, 51% were men, and 85% had bilateral CTS that required surgery. The surgeons removed a tenosynovial biopsy at the time of surgery from each of the 96 patients, a “low-risk procedure,” Dr. Hanna said.
The 10 patients with positive staining for amyloid underwent a work-up that included a comprehensive physical examination, a series of blood tests for cardiac biomarkers, an ECG, echocardiography including assessment of cardiac strain, and a technetium-99m pyrophosphate scan. This identified two patients with cardiac involvement. The examinations identified one case by the echocardiographic strain findings and the second case by the technetium pyrophosphate scan. Seven of the 10 patients with amyloid had a history of prior carpal tunnel release surgery.
The researchers also used mass spectroscopy to identify the amyloid type. Seven patients had the transthyretin subtype, including one patient with cardiac involvement; two patients had light chain amyloidosis, including the second patient with cardiac involvement. The tenth patient had inconclusive results but the researchers presumed the amyloid was of the transthyretin type, Dr. Hanna said.
The eight patients identified with amyloid but no cardiac involvement at baseline will continue to receive annual work ups to see whether their hearts become affected over time. The protocol delays a repeat technetium pyrophosphate scan until the 4th year following study entry.
The potential usefulness of early identification and treatment of cardiac amyloidosis received support in results from another study reported at the meeting. Researchers from Columbia University Medical Center, New York, and New York Presbyterian Hospital reported their retrospective, nonrandomized experience with 126 patients who had been diagnosed with transthyretin cardiac amyloidosis. Thirty of these patients had received treatment with a transthyretin-stabilizing drug, either the investigational agent tafamidis or diflunisal, while the other 96 patients received no stabilizing treatment. During a median follow-up of 2 years, patients treated with a stabilizing agent had a statistically significant 68% reduced rate of either death or orthotopic heart transplant, compared with the untreated patients in a multivariate analysis that controlled for various baseline differences between the treated and untreated patients.
[email protected]
On Twitter @mitchelzoler
AT THE HFSA ANNUAL SCIENTIFIC MEETING
Key clinical point:
Major finding: Ten of 96 patients undergoing carpal tunnel release surgery had amyloidosis, and two had cardiac involvement.
Data source: Prospective, single-center series of 96 patients undergoing carpal tunnel release surgery.
Disclosures: Dr. Hanna had no disclosures.
Tips for Living With Ataxia
Click here to download the PDF. 
Click here to download the PDF.
Click here to download the PDF.
Painful autoimmune neuropathy may mimic Guillain-Barré syndrome
Patients with an acute transient immune response that is directed against small nerve fibers can display features similar to those of Guillain-Barré syndrome, according to Nobuhiro Yuki, PhD, and associates.
The investigators described three Chinese patients with severe pain in their extremities weeks after infectious illness. Pain greatly improved in two of the patients within days (up to 1 week) of treatment with intravenous immunoglobulin. One patient who refused intravenous immunoglobulin gradually improved with 3 weeks of prednisolone treatment but did not improve as much as the other two.
The investigators found that intrathecal injections of the sera from the acute phase of these patients’ illnesses into nociceptive thermal mouse models induced a transient thermal hypersensitivity, whereas sera from 25 patients with Charcot-Marie-Tooth disease and 25 patients with chronic inflammatory demyelinating polyneuropathy who served as disease controls did not. The intrathecal injections of sera from a healthy donor or from the first two of the three described patients after recovery did not affect thermal sensitivity.
Also, patients’ sera in the acute phase strongly and widely stained small nerve fibers in the dermis of the foot pads of the mice and colocalized with a nerve marker. The sera did not react against myelinated fibers from mouse sciatic nerves. Serum IgG antibodies immunostained the dorsal horn of the lumber spinal cord during the acute phase in all patients, but none of the patients showed reactivity in the convalescent phase.
Patients’ IgG antibodies reacted against surface antigens from the neuron cell body and axon from patients’ sera, but none of the patients with Charcot-Marie-Tooth or chronic inflammatory demyelinating polyneuropathy presented a similar reaction against dorsal root ganglion neurons.
“Our case series and the cases identified in the literature suggest that an acute immune response can be directed against small fibers and exhibit similarities to Guillain-Barré syndrome, including acute preceding infectious illness, a monophasic course, and albuminocytologic dissociation,” the researchers concluded. “It is also worth pointing out that patients with ‘acute small fiber sensory neuropathy’ subsequent to infection or vaccination do not always complain of pain, suggesting a different disease entity.”
Read the full study in Muscle & Nerve (2017. doi: 10.1002/mus.25738).
Patients with an acute transient immune response that is directed against small nerve fibers can display features similar to those of Guillain-Barré syndrome, according to Nobuhiro Yuki, PhD, and associates.
The investigators described three Chinese patients with severe pain in their extremities weeks after infectious illness. Pain greatly improved in two of the patients within days (up to 1 week) of treatment with intravenous immunoglobulin. One patient who refused intravenous immunoglobulin gradually improved with 3 weeks of prednisolone treatment but did not improve as much as the other two.
The investigators found that intrathecal injections of the sera from the acute phase of these patients’ illnesses into nociceptive thermal mouse models induced a transient thermal hypersensitivity, whereas sera from 25 patients with Charcot-Marie-Tooth disease and 25 patients with chronic inflammatory demyelinating polyneuropathy who served as disease controls did not. The intrathecal injections of sera from a healthy donor or from the first two of the three described patients after recovery did not affect thermal sensitivity.
Also, patients’ sera in the acute phase strongly and widely stained small nerve fibers in the dermis of the foot pads of the mice and colocalized with a nerve marker. The sera did not react against myelinated fibers from mouse sciatic nerves. Serum IgG antibodies immunostained the dorsal horn of the lumber spinal cord during the acute phase in all patients, but none of the patients showed reactivity in the convalescent phase.
Patients’ IgG antibodies reacted against surface antigens from the neuron cell body and axon from patients’ sera, but none of the patients with Charcot-Marie-Tooth or chronic inflammatory demyelinating polyneuropathy presented a similar reaction against dorsal root ganglion neurons.
“Our case series and the cases identified in the literature suggest that an acute immune response can be directed against small fibers and exhibit similarities to Guillain-Barré syndrome, including acute preceding infectious illness, a monophasic course, and albuminocytologic dissociation,” the researchers concluded. “It is also worth pointing out that patients with ‘acute small fiber sensory neuropathy’ subsequent to infection or vaccination do not always complain of pain, suggesting a different disease entity.”
Read the full study in Muscle & Nerve (2017. doi: 10.1002/mus.25738).
Patients with an acute transient immune response that is directed against small nerve fibers can display features similar to those of Guillain-Barré syndrome, according to Nobuhiro Yuki, PhD, and associates.
The investigators described three Chinese patients with severe pain in their extremities weeks after infectious illness. Pain greatly improved in two of the patients within days (up to 1 week) of treatment with intravenous immunoglobulin. One patient who refused intravenous immunoglobulin gradually improved with 3 weeks of prednisolone treatment but did not improve as much as the other two.
The investigators found that intrathecal injections of the sera from the acute phase of these patients’ illnesses into nociceptive thermal mouse models induced a transient thermal hypersensitivity, whereas sera from 25 patients with Charcot-Marie-Tooth disease and 25 patients with chronic inflammatory demyelinating polyneuropathy who served as disease controls did not. The intrathecal injections of sera from a healthy donor or from the first two of the three described patients after recovery did not affect thermal sensitivity.
Also, patients’ sera in the acute phase strongly and widely stained small nerve fibers in the dermis of the foot pads of the mice and colocalized with a nerve marker. The sera did not react against myelinated fibers from mouse sciatic nerves. Serum IgG antibodies immunostained the dorsal horn of the lumber spinal cord during the acute phase in all patients, but none of the patients showed reactivity in the convalescent phase.
Patients’ IgG antibodies reacted against surface antigens from the neuron cell body and axon from patients’ sera, but none of the patients with Charcot-Marie-Tooth or chronic inflammatory demyelinating polyneuropathy presented a similar reaction against dorsal root ganglion neurons.
“Our case series and the cases identified in the literature suggest that an acute immune response can be directed against small fibers and exhibit similarities to Guillain-Barré syndrome, including acute preceding infectious illness, a monophasic course, and albuminocytologic dissociation,” the researchers concluded. “It is also worth pointing out that patients with ‘acute small fiber sensory neuropathy’ subsequent to infection or vaccination do not always complain of pain, suggesting a different disease entity.”
Read the full study in Muscle & Nerve (2017. doi: 10.1002/mus.25738).
FROM MUSCLE & NERVE
New trial shows thymectomy benefits myasthenia gravis
The effectiveness of thymectomy as a cure for myasthenia gravis has long been debated, but the publication of Myasthenia Gravis Thymectomy Treatment (MGTX) trial results, showing that thymectomy improved outcomes over 3 years in patients with nonthymomatous myasthenia gravis, has gone a long way toward settling the debate, Joshua R. Sonett, MD, and his coauthors noted in a feature expert opinion (J Thorac Cardiovasc Surg. 2017;154:306-9).
The MGTX trial randomized patients with nonthymomatous MG into two treatment groups: medical therapy alone or thymectomy with medical therapy (N Engl J Med. 2016;375:511-22). For uniformity, the study mandated one type of thymectomy, an extended transsternal approach. The study was 12 years in the making, with 6 years of patient accrual followed by 3 years of surveillance, Dr. Sonett and his coauthors noted.
Those markers include an average quantitative myasthenia score of 6.15 for the thymectomy group vs. 8.99 for the medical therapy group (P less than .0001); a lower dose of prednisone to attain improved neurologic status (44 mg vs. 60 mg; P less than .001); time-weighted average score on the Myasthenia Gravis Activities of Daily Living scale (2.24 vs. 3.41; P = .008); azathioprine use (17% vs. 48%; P less than .001); percentage of patients who had minimal-manifestation status at month 36 (67% vs. 47%; P = .03); and hospitalization for myasthenia-related symptoms (9% vs. 37%). “Interestingly,” the researchers wrote, “despite these quantitative results, no difference was seen in the quality of life measured surveys.”
An ancillary study, Bio-MGTX, was performed simultaneously to investigate pathologic and serum markers. “Many questions still need to be answered in regard to the role of thymectomy in MG,” Dr. Sonett and his coauthors maintained. They include an analysis of radiologic predictors of success with thymectomy, and the role of thymectomy in seronegative MG, ocular MG and elderly patients.
“Future studies may be directed at achieving a more rapid and consistent time to a complete symptom response,” they said.
The MGTX trial does support the use of high-dose prednisone induction combined with thymectomy to achieve higher complete early remission rates, but Bio-MGTX data may help to refine induction protocols. “The debate will likely continue in regard to widespread adoption of extended transsternal maximal thymectomy,” the researchers wrote. “What was categorically measured in this trial was the effect of maximal thymectomy, as sternotomy offers no particular independent therapeutic benefit.”
The structure of the MGTX trial despite its small cohort (126) “enabled the medical and surgical community to definitively answer an important question,” they noted. Nonetheless, further investigation of the role of thymectomy in MG is “sorely needed.”
Patients may need up to 3 years to achieve an optimal response, and complete cure in a shorter time frame should be the goal for each patient. Multimodal therapy should be the basis of MG treatment. “Continued progress in the management of MG will require diligent, multidisciplinary teams designing and completing prospective studies like the MGTX,” the researchers wrote.
Dr. Sonett and his coauthors had no financial relationships to disclose. The MGTX trial was funded by the U.S. National Institute of Neurological Disorders and Stroke. There was no commercial support for the trial.
In the MGTX trial, patients in the thymectomy group still needed a high average dose of prednisone, and the rates of remission may decrease over time, Michael K. Hsin, MD, of Queen Mary Hospital, Hong Kong, wrote in his invited commentary (J Thorac Cardiovasc Surg. 2017;154:310-1). But he added that the trial did finally answer in a positive manner whether thymectomy could serve a beneficial role.
He also noted that the MGTX trial left at least four questions unanswered:
• The long-term effect of thymectomy on MG status with regard to future relapse.
• The role of surgery in the era of advances in medical treatment, including azathioprine to reduce the prednisone dose and emergence of stem-cell transplantation.
• The extent to which MGTX findings can be applied to acetylcholine receptor-negative pediatric patients.
• Whether alternative techniques to extended transsternal thymectomy can achieve comparable results.
Dr. Hsin had no financial relationships to disclose.
In the MGTX trial, patients in the thymectomy group still needed a high average dose of prednisone, and the rates of remission may decrease over time, Michael K. Hsin, MD, of Queen Mary Hospital, Hong Kong, wrote in his invited commentary (J Thorac Cardiovasc Surg. 2017;154:310-1). But he added that the trial did finally answer in a positive manner whether thymectomy could serve a beneficial role.
He also noted that the MGTX trial left at least four questions unanswered:
• The long-term effect of thymectomy on MG status with regard to future relapse.
• The role of surgery in the era of advances in medical treatment, including azathioprine to reduce the prednisone dose and emergence of stem-cell transplantation.
• The extent to which MGTX findings can be applied to acetylcholine receptor-negative pediatric patients.
• Whether alternative techniques to extended transsternal thymectomy can achieve comparable results.
Dr. Hsin had no financial relationships to disclose.
In the MGTX trial, patients in the thymectomy group still needed a high average dose of prednisone, and the rates of remission may decrease over time, Michael K. Hsin, MD, of Queen Mary Hospital, Hong Kong, wrote in his invited commentary (J Thorac Cardiovasc Surg. 2017;154:310-1). But he added that the trial did finally answer in a positive manner whether thymectomy could serve a beneficial role.
He also noted that the MGTX trial left at least four questions unanswered:
• The long-term effect of thymectomy on MG status with regard to future relapse.
• The role of surgery in the era of advances in medical treatment, including azathioprine to reduce the prednisone dose and emergence of stem-cell transplantation.
• The extent to which MGTX findings can be applied to acetylcholine receptor-negative pediatric patients.
• Whether alternative techniques to extended transsternal thymectomy can achieve comparable results.
Dr. Hsin had no financial relationships to disclose.
The effectiveness of thymectomy as a cure for myasthenia gravis has long been debated, but the publication of Myasthenia Gravis Thymectomy Treatment (MGTX) trial results, showing that thymectomy improved outcomes over 3 years in patients with nonthymomatous myasthenia gravis, has gone a long way toward settling the debate, Joshua R. Sonett, MD, and his coauthors noted in a feature expert opinion (J Thorac Cardiovasc Surg. 2017;154:306-9).
The MGTX trial randomized patients with nonthymomatous MG into two treatment groups: medical therapy alone or thymectomy with medical therapy (N Engl J Med. 2016;375:511-22). For uniformity, the study mandated one type of thymectomy, an extended transsternal approach. The study was 12 years in the making, with 6 years of patient accrual followed by 3 years of surveillance, Dr. Sonett and his coauthors noted.
Those markers include an average quantitative myasthenia score of 6.15 for the thymectomy group vs. 8.99 for the medical therapy group (P less than .0001); a lower dose of prednisone to attain improved neurologic status (44 mg vs. 60 mg; P less than .001); time-weighted average score on the Myasthenia Gravis Activities of Daily Living scale (2.24 vs. 3.41; P = .008); azathioprine use (17% vs. 48%; P less than .001); percentage of patients who had minimal-manifestation status at month 36 (67% vs. 47%; P = .03); and hospitalization for myasthenia-related symptoms (9% vs. 37%). “Interestingly,” the researchers wrote, “despite these quantitative results, no difference was seen in the quality of life measured surveys.”
An ancillary study, Bio-MGTX, was performed simultaneously to investigate pathologic and serum markers. “Many questions still need to be answered in regard to the role of thymectomy in MG,” Dr. Sonett and his coauthors maintained. They include an analysis of radiologic predictors of success with thymectomy, and the role of thymectomy in seronegative MG, ocular MG and elderly patients.
“Future studies may be directed at achieving a more rapid and consistent time to a complete symptom response,” they said.
The MGTX trial does support the use of high-dose prednisone induction combined with thymectomy to achieve higher complete early remission rates, but Bio-MGTX data may help to refine induction protocols. “The debate will likely continue in regard to widespread adoption of extended transsternal maximal thymectomy,” the researchers wrote. “What was categorically measured in this trial was the effect of maximal thymectomy, as sternotomy offers no particular independent therapeutic benefit.”
The structure of the MGTX trial despite its small cohort (126) “enabled the medical and surgical community to definitively answer an important question,” they noted. Nonetheless, further investigation of the role of thymectomy in MG is “sorely needed.”
Patients may need up to 3 years to achieve an optimal response, and complete cure in a shorter time frame should be the goal for each patient. Multimodal therapy should be the basis of MG treatment. “Continued progress in the management of MG will require diligent, multidisciplinary teams designing and completing prospective studies like the MGTX,” the researchers wrote.
Dr. Sonett and his coauthors had no financial relationships to disclose. The MGTX trial was funded by the U.S. National Institute of Neurological Disorders and Stroke. There was no commercial support for the trial.
The effectiveness of thymectomy as a cure for myasthenia gravis has long been debated, but the publication of Myasthenia Gravis Thymectomy Treatment (MGTX) trial results, showing that thymectomy improved outcomes over 3 years in patients with nonthymomatous myasthenia gravis, has gone a long way toward settling the debate, Joshua R. Sonett, MD, and his coauthors noted in a feature expert opinion (J Thorac Cardiovasc Surg. 2017;154:306-9).
The MGTX trial randomized patients with nonthymomatous MG into two treatment groups: medical therapy alone or thymectomy with medical therapy (N Engl J Med. 2016;375:511-22). For uniformity, the study mandated one type of thymectomy, an extended transsternal approach. The study was 12 years in the making, with 6 years of patient accrual followed by 3 years of surveillance, Dr. Sonett and his coauthors noted.
Those markers include an average quantitative myasthenia score of 6.15 for the thymectomy group vs. 8.99 for the medical therapy group (P less than .0001); a lower dose of prednisone to attain improved neurologic status (44 mg vs. 60 mg; P less than .001); time-weighted average score on the Myasthenia Gravis Activities of Daily Living scale (2.24 vs. 3.41; P = .008); azathioprine use (17% vs. 48%; P less than .001); percentage of patients who had minimal-manifestation status at month 36 (67% vs. 47%; P = .03); and hospitalization for myasthenia-related symptoms (9% vs. 37%). “Interestingly,” the researchers wrote, “despite these quantitative results, no difference was seen in the quality of life measured surveys.”
An ancillary study, Bio-MGTX, was performed simultaneously to investigate pathologic and serum markers. “Many questions still need to be answered in regard to the role of thymectomy in MG,” Dr. Sonett and his coauthors maintained. They include an analysis of radiologic predictors of success with thymectomy, and the role of thymectomy in seronegative MG, ocular MG and elderly patients.
“Future studies may be directed at achieving a more rapid and consistent time to a complete symptom response,” they said.
The MGTX trial does support the use of high-dose prednisone induction combined with thymectomy to achieve higher complete early remission rates, but Bio-MGTX data may help to refine induction protocols. “The debate will likely continue in regard to widespread adoption of extended transsternal maximal thymectomy,” the researchers wrote. “What was categorically measured in this trial was the effect of maximal thymectomy, as sternotomy offers no particular independent therapeutic benefit.”
The structure of the MGTX trial despite its small cohort (126) “enabled the medical and surgical community to definitively answer an important question,” they noted. Nonetheless, further investigation of the role of thymectomy in MG is “sorely needed.”
Patients may need up to 3 years to achieve an optimal response, and complete cure in a shorter time frame should be the goal for each patient. Multimodal therapy should be the basis of MG treatment. “Continued progress in the management of MG will require diligent, multidisciplinary teams designing and completing prospective studies like the MGTX,” the researchers wrote.
Dr. Sonett and his coauthors had no financial relationships to disclose. The MGTX trial was funded by the U.S. National Institute of Neurological Disorders and Stroke. There was no commercial support for the trial.
FROM THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
Key clinical point: A recently published prospective randomized trial provides definitive evidence that thymectomy significantly improves outcomes of patients with myasthenia gravis.
Major finding: Patients who underwent thymectomy had an average quantitative myasthenia score of 6.15 vs. 8.99 for the medical therapy group, a significant difference.
Data source: Myasthenia Gravis Thymectomy Trial, a prospective trial of 126 patients randomized to thymectomy with medical therapy or medical therapy alone.
Disclosures: Dr. Sonett and his coauthors had no financial relationships to disclose. The MGTX trial was funded by the U.S. National Institute of Neurological Disorders and Stroke. There was no commercial support for the trial.
Course and outcome of Guillain-Barré syndrome measured in ongoing study
The International Guillain-Barré Syndrome Outcome Study (IGOS) is actively recruiting patients with Guillain-Barré Syndrome (GBS) to examine disease course and outcome, according to ClinicalTrials.gov.
IGOS is conducted by the members of the Inflammatory Neuropathy Consortium and Peripheral Nerve Society, and the researchers plan to identify clinical and biological determinants and predictors of disease course and outcome in individual patients with GBS as early as possible after onset of disease. It is a prospective study with standardized collection of clinical data and biomaterials from a large group of well-defined GBS patients during a long follow-up period. Patients will be divided into four cohorts: GBS patients with a follow-up of 1-3 years, normal controls, infectious controls, and other neurological diseases.
The primary outcome is to receive a disability score and Medical Research Council sum score within a 1-year time frame. Secondary outcomes include Overall Neuropathy Limitations Scale, Fatigue Severity Scale, EurQol EQ-5D health questionnaire, and Rasch-built Overall Disability Scale, all in a 1-year time frame. The information will be used to understand the diversity in clinical presentation and response to treatment of GBS and will also be used to develop new prognostic models to predict the clinical course and outcome accurately in individual patients with GBS.
Enrollment for the study started May 2012 and the researchers aim to enroll an estimated 4,000 participants. As of April 2017, the IGOS has enrolled more than 1,500 patients, according to the study’s website. The study is expected to be completed by January 2019. All patients with GBS or variants of GBS, including the Miller Fisher syndrome and overlap syndromes, are eligible for the study.
Currently, patients with GBS have not shown improvement over the last 20 years. It is estimated that 10%-20% of patients remain severely disabled and about 5% die from GBS.
Find the full summary here.
The International Guillain-Barré Syndrome Outcome Study (IGOS) is actively recruiting patients with Guillain-Barré Syndrome (GBS) to examine disease course and outcome, according to ClinicalTrials.gov.
IGOS is conducted by the members of the Inflammatory Neuropathy Consortium and Peripheral Nerve Society, and the researchers plan to identify clinical and biological determinants and predictors of disease course and outcome in individual patients with GBS as early as possible after onset of disease. It is a prospective study with standardized collection of clinical data and biomaterials from a large group of well-defined GBS patients during a long follow-up period. Patients will be divided into four cohorts: GBS patients with a follow-up of 1-3 years, normal controls, infectious controls, and other neurological diseases.
The primary outcome is to receive a disability score and Medical Research Council sum score within a 1-year time frame. Secondary outcomes include Overall Neuropathy Limitations Scale, Fatigue Severity Scale, EurQol EQ-5D health questionnaire, and Rasch-built Overall Disability Scale, all in a 1-year time frame. The information will be used to understand the diversity in clinical presentation and response to treatment of GBS and will also be used to develop new prognostic models to predict the clinical course and outcome accurately in individual patients with GBS.
Enrollment for the study started May 2012 and the researchers aim to enroll an estimated 4,000 participants. As of April 2017, the IGOS has enrolled more than 1,500 patients, according to the study’s website. The study is expected to be completed by January 2019. All patients with GBS or variants of GBS, including the Miller Fisher syndrome and overlap syndromes, are eligible for the study.
Currently, patients with GBS have not shown improvement over the last 20 years. It is estimated that 10%-20% of patients remain severely disabled and about 5% die from GBS.
Find the full summary here.
The International Guillain-Barré Syndrome Outcome Study (IGOS) is actively recruiting patients with Guillain-Barré Syndrome (GBS) to examine disease course and outcome, according to ClinicalTrials.gov.
IGOS is conducted by the members of the Inflammatory Neuropathy Consortium and Peripheral Nerve Society, and the researchers plan to identify clinical and biological determinants and predictors of disease course and outcome in individual patients with GBS as early as possible after onset of disease. It is a prospective study with standardized collection of clinical data and biomaterials from a large group of well-defined GBS patients during a long follow-up period. Patients will be divided into four cohorts: GBS patients with a follow-up of 1-3 years, normal controls, infectious controls, and other neurological diseases.
The primary outcome is to receive a disability score and Medical Research Council sum score within a 1-year time frame. Secondary outcomes include Overall Neuropathy Limitations Scale, Fatigue Severity Scale, EurQol EQ-5D health questionnaire, and Rasch-built Overall Disability Scale, all in a 1-year time frame. The information will be used to understand the diversity in clinical presentation and response to treatment of GBS and will also be used to develop new prognostic models to predict the clinical course and outcome accurately in individual patients with GBS.
Enrollment for the study started May 2012 and the researchers aim to enroll an estimated 4,000 participants. As of April 2017, the IGOS has enrolled more than 1,500 patients, according to the study’s website. The study is expected to be completed by January 2019. All patients with GBS or variants of GBS, including the Miller Fisher syndrome and overlap syndromes, are eligible for the study.
Currently, patients with GBS have not shown improvement over the last 20 years. It is estimated that 10%-20% of patients remain severely disabled and about 5% die from GBS.
Find the full summary here.
SUMMARY FROM CLINICALTRIALS.GOV
Gene therapy for spinal muscular atrophy shows promise in early study
BOSTON – Promising results were evident in an ongoing phase I study of a gene therapy for spinal muscular atrophy type 1 (SMA1), with children in the trial walking, talking, and moving.
After a single intravenous infusion of the therapy, AVXS-101, children in the industry-funded study achieved unexpected progress in terms of physical achievement ad survival, researchers reported at the annual meeting of the American Academy of Neurology.
Video clips showed children in the trial rolling, sitting unassisted, and showing normal levels of hand and fine motor control. No other children with SMA1 have been reported to reach any major motor milestone.
In one clip, an 18-month-old boy toddles down a hallway and carries an electronic toy to an elevator where he reaches up to press the button. “He’s basically completely back to normal. You see and examine him; it just about takes your breath away,” said the study’s lead investigator, Jerry R. Mendell, MD, a neurologist at Nationwide Children’s Hospital, Columbus, Ohio.
All 15 patients in the study were alive as of the AAN presentation, with six older than aged 2 years. Previous studies have reported various life expectancies for SMA1 patients: A 2010 Korean study of 14 SMA1 patients reported that the average lifespan was 22.8 ± 2.0 months (Korean J Pediatr. 2010 Nov;53[11]:965-70), while a 2007 Hong Kong study (n = 22) found that only 30% survived to aged 4 years and all survivors were venilator-dependent (Pediatrics. 2004 Nov;114[5]:e548-53).
The open label phase I dose-escalating study recruited 15 patients (nine under aged 9 months; six 6 under aged 6 months) with SMA1 as defined by genetic criteria and onset between birth and 6 months. All received a one-time intravenous infusion of AVXS-101 after a 1-mg/1-kg dose of prednisolone the previous day. AVXS-101 is designed to boost levels of the SMN protein via delivery of a functional human SMN gene into motor neuron cells.
The first cohort of three patients received one dose. All survived to greater than aged 30 months, although one did require respiratory assistance at about 30 months, said Dr. Mendell, professor of pediatrics, neurology, pathology, and physiology and cell Biology at Ohio State University, Columbus.
Researchers moved to a larger dose, “the highest amount of virus that’s ever been given in any clinical trial,” Dr. Mendell said. The first patient has passed 30 months of age, and 9 patients have reached at least 20 months, he noted.
In this second cohort, all patients “are able to bring hand to mouth, which is obviously important for feeding. Eleven of the 12 have good head control, and 9 of the patients can roll over. And 11 can sit without assistance,” he said.
In addition, eight can sit more than 30 seconds, and two can crawl, stand, and walk independently. Eight of 12 patients are speaking, and 11 of 12 are feeding orally.
To date, five treatment-related adverse events in four patients have been reported – all asymptomatic increases in liver function enzymes, which resolved.
The study is funded by AveXis, the company developing this gene therapy. Dr. Mendell reported compensation for consulting and research support from AveXis and Sarepta Therapeutics.
BOSTON – Promising results were evident in an ongoing phase I study of a gene therapy for spinal muscular atrophy type 1 (SMA1), with children in the trial walking, talking, and moving.
After a single intravenous infusion of the therapy, AVXS-101, children in the industry-funded study achieved unexpected progress in terms of physical achievement ad survival, researchers reported at the annual meeting of the American Academy of Neurology.
Video clips showed children in the trial rolling, sitting unassisted, and showing normal levels of hand and fine motor control. No other children with SMA1 have been reported to reach any major motor milestone.
In one clip, an 18-month-old boy toddles down a hallway and carries an electronic toy to an elevator where he reaches up to press the button. “He’s basically completely back to normal. You see and examine him; it just about takes your breath away,” said the study’s lead investigator, Jerry R. Mendell, MD, a neurologist at Nationwide Children’s Hospital, Columbus, Ohio.
All 15 patients in the study were alive as of the AAN presentation, with six older than aged 2 years. Previous studies have reported various life expectancies for SMA1 patients: A 2010 Korean study of 14 SMA1 patients reported that the average lifespan was 22.8 ± 2.0 months (Korean J Pediatr. 2010 Nov;53[11]:965-70), while a 2007 Hong Kong study (n = 22) found that only 30% survived to aged 4 years and all survivors were venilator-dependent (Pediatrics. 2004 Nov;114[5]:e548-53).
The open label phase I dose-escalating study recruited 15 patients (nine under aged 9 months; six 6 under aged 6 months) with SMA1 as defined by genetic criteria and onset between birth and 6 months. All received a one-time intravenous infusion of AVXS-101 after a 1-mg/1-kg dose of prednisolone the previous day. AVXS-101 is designed to boost levels of the SMN protein via delivery of a functional human SMN gene into motor neuron cells.
The first cohort of three patients received one dose. All survived to greater than aged 30 months, although one did require respiratory assistance at about 30 months, said Dr. Mendell, professor of pediatrics, neurology, pathology, and physiology and cell Biology at Ohio State University, Columbus.
Researchers moved to a larger dose, “the highest amount of virus that’s ever been given in any clinical trial,” Dr. Mendell said. The first patient has passed 30 months of age, and 9 patients have reached at least 20 months, he noted.
In this second cohort, all patients “are able to bring hand to mouth, which is obviously important for feeding. Eleven of the 12 have good head control, and 9 of the patients can roll over. And 11 can sit without assistance,” he said.
In addition, eight can sit more than 30 seconds, and two can crawl, stand, and walk independently. Eight of 12 patients are speaking, and 11 of 12 are feeding orally.
To date, five treatment-related adverse events in four patients have been reported – all asymptomatic increases in liver function enzymes, which resolved.
The study is funded by AveXis, the company developing this gene therapy. Dr. Mendell reported compensation for consulting and research support from AveXis and Sarepta Therapeutics.
BOSTON – Promising results were evident in an ongoing phase I study of a gene therapy for spinal muscular atrophy type 1 (SMA1), with children in the trial walking, talking, and moving.
After a single intravenous infusion of the therapy, AVXS-101, children in the industry-funded study achieved unexpected progress in terms of physical achievement ad survival, researchers reported at the annual meeting of the American Academy of Neurology.
Video clips showed children in the trial rolling, sitting unassisted, and showing normal levels of hand and fine motor control. No other children with SMA1 have been reported to reach any major motor milestone.
In one clip, an 18-month-old boy toddles down a hallway and carries an electronic toy to an elevator where he reaches up to press the button. “He’s basically completely back to normal. You see and examine him; it just about takes your breath away,” said the study’s lead investigator, Jerry R. Mendell, MD, a neurologist at Nationwide Children’s Hospital, Columbus, Ohio.
All 15 patients in the study were alive as of the AAN presentation, with six older than aged 2 years. Previous studies have reported various life expectancies for SMA1 patients: A 2010 Korean study of 14 SMA1 patients reported that the average lifespan was 22.8 ± 2.0 months (Korean J Pediatr. 2010 Nov;53[11]:965-70), while a 2007 Hong Kong study (n = 22) found that only 30% survived to aged 4 years and all survivors were venilator-dependent (Pediatrics. 2004 Nov;114[5]:e548-53).
The open label phase I dose-escalating study recruited 15 patients (nine under aged 9 months; six 6 under aged 6 months) with SMA1 as defined by genetic criteria and onset between birth and 6 months. All received a one-time intravenous infusion of AVXS-101 after a 1-mg/1-kg dose of prednisolone the previous day. AVXS-101 is designed to boost levels of the SMN protein via delivery of a functional human SMN gene into motor neuron cells.
The first cohort of three patients received one dose. All survived to greater than aged 30 months, although one did require respiratory assistance at about 30 months, said Dr. Mendell, professor of pediatrics, neurology, pathology, and physiology and cell Biology at Ohio State University, Columbus.
Researchers moved to a larger dose, “the highest amount of virus that’s ever been given in any clinical trial,” Dr. Mendell said. The first patient has passed 30 months of age, and 9 patients have reached at least 20 months, he noted.
In this second cohort, all patients “are able to bring hand to mouth, which is obviously important for feeding. Eleven of the 12 have good head control, and 9 of the patients can roll over. And 11 can sit without assistance,” he said.
In addition, eight can sit more than 30 seconds, and two can crawl, stand, and walk independently. Eight of 12 patients are speaking, and 11 of 12 are feeding orally.
To date, five treatment-related adverse events in four patients have been reported – all asymptomatic increases in liver function enzymes, which resolved.
The study is funded by AveXis, the company developing this gene therapy. Dr. Mendell reported compensation for consulting and research support from AveXis and Sarepta Therapeutics.
AT AAN 2017