Literature Review

Individuals older than 70 with nonmelanoma skin cancer may have a significantly reduced risk of developing Alzheimer’s disease, compared with individuals without nonmelanoma skin cancer, according to research published online ahead of print May 15 in Neurology. Investigators assessed 1,102 community-dwelling adults (mean age, 79) annually, and a multidisciplinary diagnostic consensus was achieved for each patient. Participants reported their cancer status and type. The researchers tested associations between nonmelanoma skin cancer and three neurocognitive disorders—only Alzheimer’s disease, any Alzheimer’s disease, and all-cause dementia. Nonmelanoma skin cancer was associated with reduced risk of only Alzheimer’s disease among subjects after adjustment for demographics, hypertension, diabetes, and coronary heart disease. No significant association was found between nonmelanoma skin cancer and subsequent development of any Alzheimer’s disease or all-cause dementia.

Consumption of fruits and vegetables that contain nicotine may reduce the risk of Parkinson’s disease, researchers reported online ahead of print May 9 in Annals of Neurology. Investigators conducted a population-based study of 490 patients with newly diagnosed Parkinson’s disease and 644 healthy controls. They examined whether Parkinson’s disease was associated with self-reported frequency of consuming fruits and vegetables from the same botanical family as tobacco, Solanaceae, including peppers, tomatoes, and potatoes. Parkinson’s disease was inversely associated with consumption of all edible Solanaceae combined, but not consumption of all other vegetables combined. Weighting edible Solanaceae by nicotine concentration strengthened the trend. Peppers specifically were inversely associated with risk of Parkinson’s disease. The potential effect of edible Solanaceae largely occurred in individuals who had never used tobacco.

The FDA has approved Nymalize, an oral solution of nimodipine, for the improvement of neurologic outcome in adults with subarachnoid hemorrhage. The drug, manufactured by Arbor Pharmaceuticals in Atlanta, is intended to reduce the incidence and severity of ischemic deficits from ruptured intracranial berry aneurysms, regardless of patients’ post-ictus neurologic condition. Before Nymalize was approved, nimodipine was available only in a gel capsule. The product is commonly administered to patients through a nasogastric tube, and health care providers sometimes extracted the product from the gel capsule with a syringe. The procedure resulted in accidental IV administrations of nimodipine instead of through the intended enteral syringe. Nymalize was designated an orphan drug, and Arbor Pharmaceuticals plans to make the product available in the coming months.

Contrary to widespread belief, African Americans may not have a lower risk of multiple sclerosis (MS) than Caucasians, researchers reported in the May 7 issue of Neurology. Investigators performed a retrospective cohort study of multiethnic, community-dwelling members of the Kaiser Permanente Southern California health plan. Overall, 496 patients were newly diagnosed with MS. The average age at diagnosis was 41.6 years, and 70.2% were women. The female preponderance was more pronounced among African American (79.3%) than in Caucasian, Hispanic, and Asian individuals with MS (67.8%, 68.1%, and 69.2%, respectively). The incidence of MS was higher in African Americans and lower in Hispanics and Asians than Caucasians. African American women had a higher risk of MS, and African American men had a similar risk of MS, compared with Caucasians.

It may be feasible to monitor patients with refractory focal seizures using an implanted seizure advisory system designed to predict seizure likelihood, according to data published online ahead of print May 2 in Lancet Neurology. Researchers implanted the advisory system in 15 patients who had between two and 12 disabling partial-onset seizures per month, a lateralized epileptogenic zone, and no history of psychogenic seizures. Within four months of implantation, 11 device-related adverse events were noted, two of which were serious. Two additional serious adverse events occurred during the first year after implantation, but they were resolved without further complication. The device met enabling criteria in 11 patients after completion of the data-collection phase, and high likelihood performance estimate sensitivities ranged from 65% to 100%.

Transplanting medial ganglionic eminence (MGE) cells into the hippocampus of adult mice with epilepsy greatly reduced the occurrence of electrographic seizures, according to a study published online ahead of print May 5 in Nature Neuroscience. The procedure also restored deficits in spatial learning, hyperactivity, and the aggressive response to handling. After transplantation, GABA progenitors migrated as far as 1,500 µm from the injection site, expressed genes and proteins characteristic of interneurons, differentiated themselves into functional inhibitory neurons, and received excitatory synaptic input. Grafts of MGE cells into the basolateral amygdala, however, restored the mice’s hyperactivity deficit, but did not affect seizure activity or other abnormal behaviors. The researchers theorized that interneurons have a crucial role in epilepsy.

The RAD6A (Ube2a) gene, which encodes for an E2 ubiquitin-conjugating enzyme, may regulate Parkin-dependent mitophagy and have a crucial role in maintaining neuronal function, according to a study published in the May 16 Molecular Cell. Researchers identified a series of patients with X-linked intellectual disability who had mutations in the RAD6A (Ube2a) gene. Drosophila deficient for dRad6 had mitochondrial failure and consequently displayed defective synaptic function. Mouse mRad6a (Ube2a) knockout and patient-derived hRad6a (Ube2a) mutant cells also had defective mitochondria. Using in vitro and in vivo ubiquitination assays, the researchers concluded that RAD6A acts as an E2 ubiquitin-conjugating enzyme that, in combination with an E3 ubiquitin ligase such as Parkin, ubiquitinates mitochondrial proteins to facilitate the clearance of dysfunctional mitochondria in cells.

The infralimbic and prelimbic prefrontal cortices may undergo functional changes to compensate for damage to the hippocampus, according to a study published online ahead of print May 15 in Proceedings of the National Academy of Sciences. Disconnection of these cortices in animals with compromised dorsal hippocampi and immediate early gene induction profiles for amygdala-projecting prefrontal cells suggested that communication and dynamic rebalancing within this prefrontal microcircuit is crucial. The infralimbic cortex normally helps to limit the generalization of contextual fear. The study results indicate that plasticity through the recruitment of alternate circuits allows the brain to compensate following damage and may result in targeted treatment of memory disorders, according to the researchers.

Among patients with psychogenic nonepileptic seizures (PNES), traumatic brain injury (TBI) may be associated with increased psychiatric comorbidities, symptom severity, poorer functioning, and increased disability, according to research published in the April issue of Epilepsia. Investigators reviewed medical records for 92 patients with EEG-confirmed PNES to assess variables including demographics, head injury, and neurologic status. Of the study population, 41 patients (44.6%) had a history of TBI, and 30 of these subjects (73%) had mild TBI. Patients with TBI had more mood disorder diagnoses, were more likely to receive disability, and had lower global functioning than patients with PNES without TBI, after adjusting for age and sex. Patients with TBI and PNES had significantly increased odds for having major depression, behavioral impulsivity, and post-traumatic stress disorder.

In patients with restless legs syndrome (RLS), glutamate may have a strong relation with arousal sleep disturbance, but not with the motor features of RLS, according to research published online ahead of print April 26 in Neurology. Investigators performed hydrogen magnetic resonance spectroscopy of the right thalamus on 28 subjects with RLS and 20 matched controls. They assessed the Glx signal (a combination of glutamate and glutamine) as a ratio to the total creatine. The Glx/Cr ratio was higher for patients with RLS than for controls and correlated significantly with wake time during the sleep period and all other RLS-related polysomnographic sleep variables except periodic leg movements during sleep (PLMS) per hour. In contrast, dopamine has a limited relation to arousal sleep disturbance and a strong relation to PLMS.

Total brain volume, gray matter volume, and white matter volume may be smaller among patients with migraine and depression than among subjects with one or neither of these conditions, according to research published online ahead of print May 22 in Neurology. Investigators assessed 4,296 participants from the population-based Age, Gene/Environment Susceptibility–Reykjavik Study for migraine between 1967 and 1991. From 2002 to 2006, clinicians diagnosed lifetime history of major depressive disorder according to DSM-IV criteria and acquired MRIs of participants’ brains. Migraineurs with depression may represent a distinct clinical phenotype with different long-term sequelae, according to the investigators. The group pointed out that the number of subjects in their study was relatively small and that their findings needed to be confirmed in future studies.

Suicide risk may be higher among military personnel with more lifetime traumatic brain injuries (TBIs), even after controlling for clinical symptom severity, according to research published online ahead of print May 15 in JAMA Psychiatry. Investigators examined 161 military personnel with suspected head injury who completed standardized self-report measures of depression, posttraumatic stress disorder (PTSD), and suicidal thoughts and behaviors. Depression, PTSD, and TBI symptom severity significantly increased with the number of TBIs. An increased incidence of lifetime suicidal thoughts or behaviors was associated with the number of TBIs, as was suicidal ideation within the past year. The number of TBIs was associated with greater suicide risk when controlling for the effects of depression, PTSD, and TBI symptom severity. A significant interaction between depression and cumulative TBIs also was found.

Focal ischemic stroke may cause pathologic disturbances in ipsilateral and contralateral brain areas, according to a study published on May 10 in PLOS One. These disturbances may be closely associated with the breakdown of the blood–brain barrier (BBB) and the accumulation of endothelial autophagosomes. Investigators randomly assigned 28 adult male rats to a control group or to occlusion of the middle cerebral artery through the intraluminal filament technique. After 60 minutes of occlusion, rats in the intervention group were reperfused. Seven days after occlusion, investigators found significant BBB alterations in the ipsilateral hemispheres of the intervention rats. The microvascular damage observed in occluded rats during the subacute phase likely revealed ischemic diaschisis and should be considered in the development of treatment strategies for stroke, said the researchers.

—Erik Greb
Senior Associate Editor

Individuals older than 70 with nonmelanoma skin cancer may have a significantly reduced risk of developing Alzheimer’s disease, compared with individuals without nonmelanoma skin cancer, according to research published online ahead of print May 15 in Neurology. Investigators assessed 1,102 community-dwelling adults (mean age, 79) annually, and a multidisciplinary diagnostic consensus was achieved for each patient. Participants reported their cancer status and type. The researchers tested associations between nonmelanoma skin cancer and three neurocognitive disorders—only Alzheimer’s disease, any Alzheimer’s disease, and all-cause dementia. Nonmelanoma skin cancer was associated with reduced risk of only Alzheimer’s disease among subjects after adjustment for demographics, hypertension, diabetes, and coronary heart disease. No significant association was found between nonmelanoma skin cancer and subsequent development of any Alzheimer’s disease or all-cause dementia.

Consumption of fruits and vegetables that contain nicotine may reduce the risk of Parkinson’s disease, researchers reported online ahead of print May 9 in Annals of Neurology. Investigators conducted a population-based study of 490 patients with newly diagnosed Parkinson’s disease and 644 healthy controls. They examined whether Parkinson’s disease was associated with self-reported frequency of consuming fruits and vegetables from the same botanical family as tobacco, Solanaceae, including peppers, tomatoes, and potatoes. Parkinson’s disease was inversely associated with consumption of all edible Solanaceae combined, but not consumption of all other vegetables combined. Weighting edible Solanaceae by nicotine concentration strengthened the trend. Peppers specifically were inversely associated with risk of Parkinson’s disease. The potential effect of edible Solanaceae largely occurred in individuals who had never used tobacco.

The FDA has approved Nymalize, an oral solution of nimodipine, for the improvement of neurologic outcome in adults with subarachnoid hemorrhage. The drug, manufactured by Arbor Pharmaceuticals in Atlanta, is intended to reduce the incidence and severity of ischemic deficits from ruptured intracranial berry aneurysms, regardless of patients’ post-ictus neurologic condition. Before Nymalize was approved, nimodipine was available only in a gel capsule. The product is commonly administered to patients through a nasogastric tube, and health care providers sometimes extracted the product from the gel capsule with a syringe. The procedure resulted in accidental IV administrations of nimodipine instead of through the intended enteral syringe. Nymalize was designated an orphan drug, and Arbor Pharmaceuticals plans to make the product available in the coming months.

Contrary to widespread belief, African Americans may not have a lower risk of multiple sclerosis (MS) than Caucasians, researchers reported in the May 7 issue of Neurology. Investigators performed a retrospective cohort study of multiethnic, community-dwelling members of the Kaiser Permanente Southern California health plan. Overall, 496 patients were newly diagnosed with MS. The average age at diagnosis was 41.6 years, and 70.2% were women. The female preponderance was more pronounced among African American (79.3%) than in Caucasian, Hispanic, and Asian individuals with MS (67.8%, 68.1%, and 69.2%, respectively). The incidence of MS was higher in African Americans and lower in Hispanics and Asians than Caucasians. African American women had a higher risk of MS, and African American men had a similar risk of MS, compared with Caucasians.

It may be feasible to monitor patients with refractory focal seizures using an implanted seizure advisory system designed to predict seizure likelihood, according to data published online ahead of print May 2 in Lancet Neurology. Researchers implanted the advisory system in 15 patients who had between two and 12 disabling partial-onset seizures per month, a lateralized epileptogenic zone, and no history of psychogenic seizures. Within four months of implantation, 11 device-related adverse events were noted, two of which were serious. Two additional serious adverse events occurred during the first year after implantation, but they were resolved without further complication. The device met enabling criteria in 11 patients after completion of the data-collection phase, and high likelihood performance estimate sensitivities ranged from 65% to 100%.

Transplanting medial ganglionic eminence (MGE) cells into the hippocampus of adult mice with epilepsy greatly reduced the occurrence of electrographic seizures, according to a study published online ahead of print May 5 in Nature Neuroscience. The procedure also restored deficits in spatial learning, hyperactivity, and the aggressive response to handling. After transplantation, GABA progenitors migrated as far as 1,500 µm from the injection site, expressed genes and proteins characteristic of interneurons, differentiated themselves into functional inhibitory neurons, and received excitatory synaptic input. Grafts of MGE cells into the basolateral amygdala, however, restored the mice’s hyperactivity deficit, but did not affect seizure activity or other abnormal behaviors. The researchers theorized that interneurons have a crucial role in epilepsy.

The RAD6A (Ube2a) gene, which encodes for an E2 ubiquitin-conjugating enzyme, may regulate Parkin-dependent mitophagy and have a crucial role in maintaining neuronal function, according to a study published in the May 16 Molecular Cell. Researchers identified a series of patients with X-linked intellectual disability who had mutations in the RAD6A (Ube2a) gene. Drosophila deficient for dRad6 had mitochondrial failure and consequently displayed defective synaptic function. Mouse mRad6a (Ube2a) knockout and patient-derived hRad6a (Ube2a) mutant cells also had defective mitochondria. Using in vitro and in vivo ubiquitination assays, the researchers concluded that RAD6A acts as an E2 ubiquitin-conjugating enzyme that, in combination with an E3 ubiquitin ligase such as Parkin, ubiquitinates mitochondrial proteins to facilitate the clearance of dysfunctional mitochondria in cells.

The infralimbic and prelimbic prefrontal cortices may undergo functional changes to compensate for damage to the hippocampus, according to a study published online ahead of print May 15 in Proceedings of the National Academy of Sciences. Disconnection of these cortices in animals with compromised dorsal hippocampi and immediate early gene induction profiles for amygdala-projecting prefrontal cells suggested that communication and dynamic rebalancing within this prefrontal microcircuit is crucial. The infralimbic cortex normally helps to limit the generalization of contextual fear. The study results indicate that plasticity through the recruitment of alternate circuits allows the brain to compensate following damage and may result in targeted treatment of memory disorders, according to the researchers.

Among patients with psychogenic nonepileptic seizures (PNES), traumatic brain injury (TBI) may be associated with increased psychiatric comorbidities, symptom severity, poorer functioning, and increased disability, according to research published in the April issue of Epilepsia. Investigators reviewed medical records for 92 patients with EEG-confirmed PNES to assess variables including demographics, head injury, and neurologic status. Of the study population, 41 patients (44.6%) had a history of TBI, and 30 of these subjects (73%) had mild TBI. Patients with TBI had more mood disorder diagnoses, were more likely to receive disability, and had lower global functioning than patients with PNES without TBI, after adjusting for age and sex. Patients with TBI and PNES had significantly increased odds for having major depression, behavioral impulsivity, and post-traumatic stress disorder.

In patients with restless legs syndrome (RLS), glutamate may have a strong relation with arousal sleep disturbance, but not with the motor features of RLS, according to research published online ahead of print April 26 in Neurology. Investigators performed hydrogen magnetic resonance spectroscopy of the right thalamus on 28 subjects with RLS and 20 matched controls. They assessed the Glx signal (a combination of glutamate and glutamine) as a ratio to the total creatine. The Glx/Cr ratio was higher for patients with RLS than for controls and correlated significantly with wake time during the sleep period and all other RLS-related polysomnographic sleep variables except periodic leg movements during sleep (PLMS) per hour. In contrast, dopamine has a limited relation to arousal sleep disturbance and a strong relation to PLMS.

Total brain volume, gray matter volume, and white matter volume may be smaller among patients with migraine and depression than among subjects with one or neither of these conditions, according to research published online ahead of print May 22 in Neurology. Investigators assessed 4,296 participants from the population-based Age, Gene/Environment Susceptibility–Reykjavik Study for migraine between 1967 and 1991. From 2002 to 2006, clinicians diagnosed lifetime history of major depressive disorder according to DSM-IV criteria and acquired MRIs of participants’ brains. Migraineurs with depression may represent a distinct clinical phenotype with different long-term sequelae, according to the investigators. The group pointed out that the number of subjects in their study was relatively small and that their findings needed to be confirmed in future studies.

Suicide risk may be higher among military personnel with more lifetime traumatic brain injuries (TBIs), even after controlling for clinical symptom severity, according to research published online ahead of print May 15 in JAMA Psychiatry. Investigators examined 161 military personnel with suspected head injury who completed standardized self-report measures of depression, posttraumatic stress disorder (PTSD), and suicidal thoughts and behaviors. Depression, PTSD, and TBI symptom severity significantly increased with the number of TBIs. An increased incidence of lifetime suicidal thoughts or behaviors was associated with the number of TBIs, as was suicidal ideation within the past year. The number of TBIs was associated with greater suicide risk when controlling for the effects of depression, PTSD, and TBI symptom severity. A significant interaction between depression and cumulative TBIs also was found.

Focal ischemic stroke may cause pathologic disturbances in ipsilateral and contralateral brain areas, according to a study published on May 10 in PLOS One. These disturbances may be closely associated with the breakdown of the blood–brain barrier (BBB) and the accumulation of endothelial autophagosomes. Investigators randomly assigned 28 adult male rats to a control group or to occlusion of the middle cerebral artery through the intraluminal filament technique. After 60 minutes of occlusion, rats in the intervention group were reperfused. Seven days after occlusion, investigators found significant BBB alterations in the ipsilateral hemispheres of the intervention rats. The microvascular damage observed in occluded rats during the subacute phase likely revealed ischemic diaschisis and should be considered in the development of treatment strategies for stroke, said the researchers.

—Erik Greb
Senior Associate Editor

Individuals older than 70 with nonmelanoma skin cancer may have a significantly reduced risk of developing Alzheimer’s disease, compared with individuals without nonmelanoma skin cancer, according to research published online ahead of print May 15 in Neurology. Investigators assessed 1,102 community-dwelling adults (mean age, 79) annually, and a multidisciplinary diagnostic consensus was achieved for each patient. Participants reported their cancer status and type. The researchers tested associations between nonmelanoma skin cancer and three neurocognitive disorders—only Alzheimer’s disease, any Alzheimer’s disease, and all-cause dementia. Nonmelanoma skin cancer was associated with reduced risk of only Alzheimer’s disease among subjects after adjustment for demographics, hypertension, diabetes, and coronary heart disease. No significant association was found between nonmelanoma skin cancer and subsequent development of any Alzheimer’s disease or all-cause dementia.

Consumption of fruits and vegetables that contain nicotine may reduce the risk of Parkinson’s disease, researchers reported online ahead of print May 9 in Annals of Neurology. Investigators conducted a population-based study of 490 patients with newly diagnosed Parkinson’s disease and 644 healthy controls. They examined whether Parkinson’s disease was associated with self-reported frequency of consuming fruits and vegetables from the same botanical family as tobacco, Solanaceae, including peppers, tomatoes, and potatoes. Parkinson’s disease was inversely associated with consumption of all edible Solanaceae combined, but not consumption of all other vegetables combined. Weighting edible Solanaceae by nicotine concentration strengthened the trend. Peppers specifically were inversely associated with risk of Parkinson’s disease. The potential effect of edible Solanaceae largely occurred in individuals who had never used tobacco.

The FDA has approved Nymalize, an oral solution of nimodipine, for the improvement of neurologic outcome in adults with subarachnoid hemorrhage. The drug, manufactured by Arbor Pharmaceuticals in Atlanta, is intended to reduce the incidence and severity of ischemic deficits from ruptured intracranial berry aneurysms, regardless of patients’ post-ictus neurologic condition. Before Nymalize was approved, nimodipine was available only in a gel capsule. The product is commonly administered to patients through a nasogastric tube, and health care providers sometimes extracted the product from the gel capsule with a syringe. The procedure resulted in accidental IV administrations of nimodipine instead of through the intended enteral syringe. Nymalize was designated an orphan drug, and Arbor Pharmaceuticals plans to make the product available in the coming months.

Contrary to widespread belief, African Americans may not have a lower risk of multiple sclerosis (MS) than Caucasians, researchers reported in the May 7 issue of Neurology. Investigators performed a retrospective cohort study of multiethnic, community-dwelling members of the Kaiser Permanente Southern California health plan. Overall, 496 patients were newly diagnosed with MS. The average age at diagnosis was 41.6 years, and 70.2% were women. The female preponderance was more pronounced among African American (79.3%) than in Caucasian, Hispanic, and Asian individuals with MS (67.8%, 68.1%, and 69.2%, respectively). The incidence of MS was higher in African Americans and lower in Hispanics and Asians than Caucasians. African American women had a higher risk of MS, and African American men had a similar risk of MS, compared with Caucasians.

It may be feasible to monitor patients with refractory focal seizures using an implanted seizure advisory system designed to predict seizure likelihood, according to data published online ahead of print May 2 in Lancet Neurology. Researchers implanted the advisory system in 15 patients who had between two and 12 disabling partial-onset seizures per month, a lateralized epileptogenic zone, and no history of psychogenic seizures. Within four months of implantation, 11 device-related adverse events were noted, two of which were serious. Two additional serious adverse events occurred during the first year after implantation, but they were resolved without further complication. The device met enabling criteria in 11 patients after completion of the data-collection phase, and high likelihood performance estimate sensitivities ranged from 65% to 100%.

Transplanting medial ganglionic eminence (MGE) cells into the hippocampus of adult mice with epilepsy greatly reduced the occurrence of electrographic seizures, according to a study published online ahead of print May 5 in Nature Neuroscience. The procedure also restored deficits in spatial learning, hyperactivity, and the aggressive response to handling. After transplantation, GABA progenitors migrated as far as 1,500 µm from the injection site, expressed genes and proteins characteristic of interneurons, differentiated themselves into functional inhibitory neurons, and received excitatory synaptic input. Grafts of MGE cells into the basolateral amygdala, however, restored the mice’s hyperactivity deficit, but did not affect seizure activity or other abnormal behaviors. The researchers theorized that interneurons have a crucial role in epilepsy.

The RAD6A (Ube2a) gene, which encodes for an E2 ubiquitin-conjugating enzyme, may regulate Parkin-dependent mitophagy and have a crucial role in maintaining neuronal function, according to a study published in the May 16 Molecular Cell. Researchers identified a series of patients with X-linked intellectual disability who had mutations in the RAD6A (Ube2a) gene. Drosophila deficient for dRad6 had mitochondrial failure and consequently displayed defective synaptic function. Mouse mRad6a (Ube2a) knockout and patient-derived hRad6a (Ube2a) mutant cells also had defective mitochondria. Using in vitro and in vivo ubiquitination assays, the researchers concluded that RAD6A acts as an E2 ubiquitin-conjugating enzyme that, in combination with an E3 ubiquitin ligase such as Parkin, ubiquitinates mitochondrial proteins to facilitate the clearance of dysfunctional mitochondria in cells.

The infralimbic and prelimbic prefrontal cortices may undergo functional changes to compensate for damage to the hippocampus, according to a study published online ahead of print May 15 in Proceedings of the National Academy of Sciences. Disconnection of these cortices in animals with compromised dorsal hippocampi and immediate early gene induction profiles for amygdala-projecting prefrontal cells suggested that communication and dynamic rebalancing within this prefrontal microcircuit is crucial. The infralimbic cortex normally helps to limit the generalization of contextual fear. The study results indicate that plasticity through the recruitment of alternate circuits allows the brain to compensate following damage and may result in targeted treatment of memory disorders, according to the researchers.

Among patients with psychogenic nonepileptic seizures (PNES), traumatic brain injury (TBI) may be associated with increased psychiatric comorbidities, symptom severity, poorer functioning, and increased disability, according to research published in the April issue of Epilepsia. Investigators reviewed medical records for 92 patients with EEG-confirmed PNES to assess variables including demographics, head injury, and neurologic status. Of the study population, 41 patients (44.6%) had a history of TBI, and 30 of these subjects (73%) had mild TBI. Patients with TBI had more mood disorder diagnoses, were more likely to receive disability, and had lower global functioning than patients with PNES without TBI, after adjusting for age and sex. Patients with TBI and PNES had significantly increased odds for having major depression, behavioral impulsivity, and post-traumatic stress disorder.

In patients with restless legs syndrome (RLS), glutamate may have a strong relation with arousal sleep disturbance, but not with the motor features of RLS, according to research published online ahead of print April 26 in Neurology. Investigators performed hydrogen magnetic resonance spectroscopy of the right thalamus on 28 subjects with RLS and 20 matched controls. They assessed the Glx signal (a combination of glutamate and glutamine) as a ratio to the total creatine. The Glx/Cr ratio was higher for patients with RLS than for controls and correlated significantly with wake time during the sleep period and all other RLS-related polysomnographic sleep variables except periodic leg movements during sleep (PLMS) per hour. In contrast, dopamine has a limited relation to arousal sleep disturbance and a strong relation to PLMS.

Total brain volume, gray matter volume, and white matter volume may be smaller among patients with migraine and depression than among subjects with one or neither of these conditions, according to research published online ahead of print May 22 in Neurology. Investigators assessed 4,296 participants from the population-based Age, Gene/Environment Susceptibility–Reykjavik Study for migraine between 1967 and 1991. From 2002 to 2006, clinicians diagnosed lifetime history of major depressive disorder according to DSM-IV criteria and acquired MRIs of participants’ brains. Migraineurs with depression may represent a distinct clinical phenotype with different long-term sequelae, according to the investigators. The group pointed out that the number of subjects in their study was relatively small and that their findings needed to be confirmed in future studies.

Suicide risk may be higher among military personnel with more lifetime traumatic brain injuries (TBIs), even after controlling for clinical symptom severity, according to research published online ahead of print May 15 in JAMA Psychiatry. Investigators examined 161 military personnel with suspected head injury who completed standardized self-report measures of depression, posttraumatic stress disorder (PTSD), and suicidal thoughts and behaviors. Depression, PTSD, and TBI symptom severity significantly increased with the number of TBIs. An increased incidence of lifetime suicidal thoughts or behaviors was associated with the number of TBIs, as was suicidal ideation within the past year. The number of TBIs was associated with greater suicide risk when controlling for the effects of depression, PTSD, and TBI symptom severity. A significant interaction between depression and cumulative TBIs also was found.

Focal ischemic stroke may cause pathologic disturbances in ipsilateral and contralateral brain areas, according to a study published on May 10 in PLOS One. These disturbances may be closely associated with the breakdown of the blood–brain barrier (BBB) and the accumulation of endothelial autophagosomes. Investigators randomly assigned 28 adult male rats to a control group or to occlusion of the middle cerebral artery through the intraluminal filament technique. After 60 minutes of occlusion, rats in the intervention group were reperfused. Seven days after occlusion, investigators found significant BBB alterations in the ipsilateral hemispheres of the intervention rats. The microvascular damage observed in occluded rats during the subacute phase likely revealed ischemic diaschisis and should be considered in the development of treatment strategies for stroke, said the researchers.

—Erik Greb
Senior Associate Editor

The word pain originates from the Latin word poena, meaning punishment, an accurate descriptor of how chronic pain affects the daily lives of millions of afflicted individuals. A 2011 Institute of Medicine report, Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education and Research, states that pain costs American society $560 to $635 billion annually, figures based on both health care costs and lost productivity. Pain has an immense impact on quality of life, with high rates of depression, suicidal ideation, and drug abuse in patients with chronic pain. Although most statistics on pain in America are based on individuals age 21 or older, the incidence of pain in children and adolescents may be as high as 20%.¹

In the current issue of Pediatrics, Drs. Oaklander and Klein address a poorly recognized but important national health problem: chronic pain in children and teenagers. In a study of 41 subjects averaging 12 years of age with chronic widespread pain, the researchers report clear functional and pathologic evidence of small-fiber neuropathy in all but one child with objective treatment responses to immunomodulatory therapy. Their findings provide physicians the data required for evidence-based decisions on not only the diagnostic work-up, but also the treatment of children with chronic widespread pain. It is imperative that the medical community listen to Drs. Oaklander and Klein and recognize chronic widespread pain in children as a diagnosable small-fiber neuropathy with clear treatment options.

—Eva L. Feldman, MD, PhD
Russell N. DeJong Professor of Neurology
Director, A. Alfred Taubman Medical Research Institute
Director, Program for Neurology Research and Discovery
University of Michigan, Ann Arbor

Reference
1. Institute of Medicine of the National Academies. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. Washington, DC: National Academies Press; 2011.

The word pain originates from the Latin word poena, meaning punishment, an accurate descriptor of how chronic pain affects the daily lives of millions of afflicted individuals. A 2011 Institute of Medicine report, Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education and Research, states that pain costs American society $560 to $635 billion annually, figures based on both health care costs and lost productivity. Pain has an immense impact on quality of life, with high rates of depression, suicidal ideation, and drug abuse in patients with chronic pain. Although most statistics on pain in America are based on individuals age 21 or older, the incidence of pain in children and adolescents may be as high as 20%.¹

In the current issue of Pediatrics, Drs. Oaklander and Klein address a poorly recognized but important national health problem: chronic pain in children and teenagers. In a study of 41 subjects averaging 12 years of age with chronic widespread pain, the researchers report clear functional and pathologic evidence of small-fiber neuropathy in all but one child with objective treatment responses to immunomodulatory therapy. Their findings provide physicians the data required for evidence-based decisions on not only the diagnostic work-up, but also the treatment of children with chronic widespread pain. It is imperative that the medical community listen to Drs. Oaklander and Klein and recognize chronic widespread pain in children as a diagnosable small-fiber neuropathy with clear treatment options.

—Eva L. Feldman, MD, PhD
Russell N. DeJong Professor of Neurology
Director, A. Alfred Taubman Medical Research Institute
Director, Program for Neurology Research and Discovery
University of Michigan, Ann Arbor

Reference
1. Institute of Medicine of the National Academies. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. Washington, DC: National Academies Press; 2011.

The word pain originates from the Latin word poena, meaning punishment, an accurate descriptor of how chronic pain affects the daily lives of millions of afflicted individuals. A 2011 Institute of Medicine report, Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education and Research, states that pain costs American society $560 to $635 billion annually, figures based on both health care costs and lost productivity. Pain has an immense impact on quality of life, with high rates of depression, suicidal ideation, and drug abuse in patients with chronic pain. Although most statistics on pain in America are based on individuals age 21 or older, the incidence of pain in children and adolescents may be as high as 20%.¹

In the current issue of Pediatrics, Drs. Oaklander and Klein address a poorly recognized but important national health problem: chronic pain in children and teenagers. In a study of 41 subjects averaging 12 years of age with chronic widespread pain, the researchers report clear functional and pathologic evidence of small-fiber neuropathy in all but one child with objective treatment responses to immunomodulatory therapy. Their findings provide physicians the data required for evidence-based decisions on not only the diagnostic work-up, but also the treatment of children with chronic widespread pain. It is imperative that the medical community listen to Drs. Oaklander and Klein and recognize chronic widespread pain in children as a diagnosable small-fiber neuropathy with clear treatment options.

—Eva L. Feldman, MD, PhD
Russell N. DeJong Professor of Neurology
Director, A. Alfred Taubman Medical Research Institute
Director, Program for Neurology Research and Discovery
University of Michigan, Ann Arbor

Reference
1. Institute of Medicine of the National Academies. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. Washington, DC: National Academies Press; 2011.

In a large series of adult and pediatric patients with juvenile-onset, unexplained, chronic widespread pain, more than half met rigorous, multi-test diagnostic criteria for small-fiber polyneuropathy (SFPN), according to a report in the April issue of Pediatrics. This finding, said lead author Anne Louise Oaklander, MD, PhD, extends the age range of acquired SFPN into young adulthood, adolescence, and even early childhood.

Dr. Oaklander and coauthor Max M. Klein, PhD, both affiliated with Massachusetts General Hospital and Harvard Medical School in Boston, evaluated 41 consecutive patients with unexplained widespread pain beginning before age 21. Most had extensive medical records that were extracted for the results of objective diagnostic testing for SFPN, which consisted of neurodiagnostic skin biopsy, nerve biopsy, and autonomic function testing. Secondary information came from subjects’ histories, symptoms, examinations, all other tests, and treatments. Healthy, demographically matched volunteers served as controls for SFPN tests.

“We chose for this initial characterization paper to focus on the youngest group with this disease, because they lacked potentially confounding conditions,” Dr. Oaklander told Neurology Reviews. “It can be hard to ascertain the specific cause of peripheral neuropathy in older adults because they have so many potentially neuropathic exposures and conditions. Here, by focusing on children, we were able to study a pure population in whom exposure to alcohol, toxins, nutritional deficiencies, cancer, and diabetes, were absent. The high signal-to-noise ratio enabled us to home in on the likelihood of autoimmune causality in most. Because of the different age-range and causality, we call this juvenile-onset small-fiber polyneuropathy, or JOSeFINE, to distinguish it from classical SFPN of older adults.”

Subjects included children from other countries and various races, demonstrating that JOSeFINE is present outside the US. Seventy-three percent of patients were female. Nearly 70% had been chronically disabled from school or work, and the same number (68%) had hospitalizations. Objective testing diagnosed definite SFPN in 59% and probable SFPN in 17%. Only one of the 41 subjects had entirely normal SFPN test results. Ninety-eight percent of patients also had other complaints thought to represent autonomic symptoms of SFPN (90% had cardiovascular, 82% had gastrointestinal, and 34% had urologic complaints). In addition, 83% reported chronic fatigue and 63% had chronic headache. Neurologic examinations identified reduced sensation in 68% and vasomotor abnormalities in 55%, including 23% with the erythromelalgia variant that produces areas of redness and burning that patients treat by cooling.

In addition, this study investigated the underlying causes of SFPN in this cohort. Several lines of evidence suggested immunologic problems. For example, past histories for 33% of subjects were notable only for history of other autoimmune illness, and extensive blood and urine tests revealed only serologic markers of disordered immunity in 89% of patients. In addition, some patients improved after immunomodulatory treatments. Corticosteroids or IV immune globulin objectively and subjectively benefited 12 of 15 patients (80%).

“This case series provides a new hypothesis about juvenile-onset, unexplained, acquired chronic widespread pain syndromes, implicating acquired SFPN, a biologically plausible diagnosis not previously recognized in children,” Drs. Oaklander and Klein wrote in their published paper. The data, they contend, suggest that SFPN can develop in children as young as preschool age and that juvenile-onset SFPN can persist for decades into adulthood.

“I would like to emphasize that this is not a disease only of children,” said Dr. Oaklander. “In fact, most patients were young adults by the time they reached us for diagnosis. Additionally, we have other patients who were not included in this study whose illness began when they were in their 20s, 30s, and even 40s. We have one older man in his 60s, but clearly the age range of JOSeFINE is different from the type of neuropathy that we associate with diabetes, cancers, and toxic exposures.

“Perhaps the most common label for these patients was pediatric fibromyalgia,” Dr. Oaklander continued. “Others had been called sero-negative Lyme or other vague descriptors. Basically, these are patients who kick around every hospital and pain clinic without a diagnosis. Now, for the first time, we’re offering a framework in which to organize care, with recommended examinations to perform, recommended diagnostic tests, and nonrecommended diagnostic tests—lumbar puncture is not useful, MRI is not useful. We homed in on the tests that are useful—skin biopsy, autonomic function testing—and we identified the blood tests that were most likely to provide supportive evidence—four specific blood tests associated with dysimmunity. Having a specific diagnosis to test for and treat when present may reduce ineffective, costly, and potentially harmful tests and treatments and permit objective testing and definitive treatment of some patients.”

In addition, the researchers said their results “demonstrate the need for pediatric norms for tests of SFPN, and they provide new testable hypotheses for clinical and basic research study that we are now engaged in.”

—Glenn S. Williams
Vice President, Group Editor

Suggested Reading
Oaklander AL, Klein MM. Evidence of small-fiber polyneuropathy in unexplained, juvenile-onset, widespread pain syndromes. Pediatrics. 2013;131(4):e1091-1100. 

In a large series of adult and pediatric patients with juvenile-onset, unexplained, chronic widespread pain, more than half met rigorous, multi-test diagnostic criteria for small-fiber polyneuropathy (SFPN), according to a report in the April issue of Pediatrics. This finding, said lead author Anne Louise Oaklander, MD, PhD, extends the age range of acquired SFPN into young adulthood, adolescence, and even early childhood.

Dr. Oaklander and coauthor Max M. Klein, PhD, both affiliated with Massachusetts General Hospital and Harvard Medical School in Boston, evaluated 41 consecutive patients with unexplained widespread pain beginning before age 21. Most had extensive medical records that were extracted for the results of objective diagnostic testing for SFPN, which consisted of neurodiagnostic skin biopsy, nerve biopsy, and autonomic function testing. Secondary information came from subjects’ histories, symptoms, examinations, all other tests, and treatments. Healthy, demographically matched volunteers served as controls for SFPN tests.

“We chose for this initial characterization paper to focus on the youngest group with this disease, because they lacked potentially confounding conditions,” Dr. Oaklander told Neurology Reviews. “It can be hard to ascertain the specific cause of peripheral neuropathy in older adults because they have so many potentially neuropathic exposures and conditions. Here, by focusing on children, we were able to study a pure population in whom exposure to alcohol, toxins, nutritional deficiencies, cancer, and diabetes, were absent. The high signal-to-noise ratio enabled us to home in on the likelihood of autoimmune causality in most. Because of the different age-range and causality, we call this juvenile-onset small-fiber polyneuropathy, or JOSeFINE, to distinguish it from classical SFPN of older adults.”

Subjects included children from other countries and various races, demonstrating that JOSeFINE is present outside the US. Seventy-three percent of patients were female. Nearly 70% had been chronically disabled from school or work, and the same number (68%) had hospitalizations. Objective testing diagnosed definite SFPN in 59% and probable SFPN in 17%. Only one of the 41 subjects had entirely normal SFPN test results. Ninety-eight percent of patients also had other complaints thought to represent autonomic symptoms of SFPN (90% had cardiovascular, 82% had gastrointestinal, and 34% had urologic complaints). In addition, 83% reported chronic fatigue and 63% had chronic headache. Neurologic examinations identified reduced sensation in 68% and vasomotor abnormalities in 55%, including 23% with the erythromelalgia variant that produces areas of redness and burning that patients treat by cooling.

In addition, this study investigated the underlying causes of SFPN in this cohort. Several lines of evidence suggested immunologic problems. For example, past histories for 33% of subjects were notable only for history of other autoimmune illness, and extensive blood and urine tests revealed only serologic markers of disordered immunity in 89% of patients. In addition, some patients improved after immunomodulatory treatments. Corticosteroids or IV immune globulin objectively and subjectively benefited 12 of 15 patients (80%).

“This case series provides a new hypothesis about juvenile-onset, unexplained, acquired chronic widespread pain syndromes, implicating acquired SFPN, a biologically plausible diagnosis not previously recognized in children,” Drs. Oaklander and Klein wrote in their published paper. The data, they contend, suggest that SFPN can develop in children as young as preschool age and that juvenile-onset SFPN can persist for decades into adulthood.

“I would like to emphasize that this is not a disease only of children,” said Dr. Oaklander. “In fact, most patients were young adults by the time they reached us for diagnosis. Additionally, we have other patients who were not included in this study whose illness began when they were in their 20s, 30s, and even 40s. We have one older man in his 60s, but clearly the age range of JOSeFINE is different from the type of neuropathy that we associate with diabetes, cancers, and toxic exposures.

“Perhaps the most common label for these patients was pediatric fibromyalgia,” Dr. Oaklander continued. “Others had been called sero-negative Lyme or other vague descriptors. Basically, these are patients who kick around every hospital and pain clinic without a diagnosis. Now, for the first time, we’re offering a framework in which to organize care, with recommended examinations to perform, recommended diagnostic tests, and nonrecommended diagnostic tests—lumbar puncture is not useful, MRI is not useful. We homed in on the tests that are useful—skin biopsy, autonomic function testing—and we identified the blood tests that were most likely to provide supportive evidence—four specific blood tests associated with dysimmunity. Having a specific diagnosis to test for and treat when present may reduce ineffective, costly, and potentially harmful tests and treatments and permit objective testing and definitive treatment of some patients.”

In addition, the researchers said their results “demonstrate the need for pediatric norms for tests of SFPN, and they provide new testable hypotheses for clinical and basic research study that we are now engaged in.”

—Glenn S. Williams
Vice President, Group Editor

Suggested Reading
Oaklander AL, Klein MM. Evidence of small-fiber polyneuropathy in unexplained, juvenile-onset, widespread pain syndromes. Pediatrics. 2013;131(4):e1091-1100. 

In a large series of adult and pediatric patients with juvenile-onset, unexplained, chronic widespread pain, more than half met rigorous, multi-test diagnostic criteria for small-fiber polyneuropathy (SFPN), according to a report in the April issue of Pediatrics. This finding, said lead author Anne Louise Oaklander, MD, PhD, extends the age range of acquired SFPN into young adulthood, adolescence, and even early childhood.

Dr. Oaklander and coauthor Max M. Klein, PhD, both affiliated with Massachusetts General Hospital and Harvard Medical School in Boston, evaluated 41 consecutive patients with unexplained widespread pain beginning before age 21. Most had extensive medical records that were extracted for the results of objective diagnostic testing for SFPN, which consisted of neurodiagnostic skin biopsy, nerve biopsy, and autonomic function testing. Secondary information came from subjects’ histories, symptoms, examinations, all other tests, and treatments. Healthy, demographically matched volunteers served as controls for SFPN tests.

“We chose for this initial characterization paper to focus on the youngest group with this disease, because they lacked potentially confounding conditions,” Dr. Oaklander told Neurology Reviews. “It can be hard to ascertain the specific cause of peripheral neuropathy in older adults because they have so many potentially neuropathic exposures and conditions. Here, by focusing on children, we were able to study a pure population in whom exposure to alcohol, toxins, nutritional deficiencies, cancer, and diabetes, were absent. The high signal-to-noise ratio enabled us to home in on the likelihood of autoimmune causality in most. Because of the different age-range and causality, we call this juvenile-onset small-fiber polyneuropathy, or JOSeFINE, to distinguish it from classical SFPN of older adults.”

Subjects included children from other countries and various races, demonstrating that JOSeFINE is present outside the US. Seventy-three percent of patients were female. Nearly 70% had been chronically disabled from school or work, and the same number (68%) had hospitalizations. Objective testing diagnosed definite SFPN in 59% and probable SFPN in 17%. Only one of the 41 subjects had entirely normal SFPN test results. Ninety-eight percent of patients also had other complaints thought to represent autonomic symptoms of SFPN (90% had cardiovascular, 82% had gastrointestinal, and 34% had urologic complaints). In addition, 83% reported chronic fatigue and 63% had chronic headache. Neurologic examinations identified reduced sensation in 68% and vasomotor abnormalities in 55%, including 23% with the erythromelalgia variant that produces areas of redness and burning that patients treat by cooling.

In addition, this study investigated the underlying causes of SFPN in this cohort. Several lines of evidence suggested immunologic problems. For example, past histories for 33% of subjects were notable only for history of other autoimmune illness, and extensive blood and urine tests revealed only serologic markers of disordered immunity in 89% of patients. In addition, some patients improved after immunomodulatory treatments. Corticosteroids or IV immune globulin objectively and subjectively benefited 12 of 15 patients (80%).

“This case series provides a new hypothesis about juvenile-onset, unexplained, acquired chronic widespread pain syndromes, implicating acquired SFPN, a biologically plausible diagnosis not previously recognized in children,” Drs. Oaklander and Klein wrote in their published paper. The data, they contend, suggest that SFPN can develop in children as young as preschool age and that juvenile-onset SFPN can persist for decades into adulthood.

“I would like to emphasize that this is not a disease only of children,” said Dr. Oaklander. “In fact, most patients were young adults by the time they reached us for diagnosis. Additionally, we have other patients who were not included in this study whose illness began when they were in their 20s, 30s, and even 40s. We have one older man in his 60s, but clearly the age range of JOSeFINE is different from the type of neuropathy that we associate with diabetes, cancers, and toxic exposures.

“Perhaps the most common label for these patients was pediatric fibromyalgia,” Dr. Oaklander continued. “Others had been called sero-negative Lyme or other vague descriptors. Basically, these are patients who kick around every hospital and pain clinic without a diagnosis. Now, for the first time, we’re offering a framework in which to organize care, with recommended examinations to perform, recommended diagnostic tests, and nonrecommended diagnostic tests—lumbar puncture is not useful, MRI is not useful. We homed in on the tests that are useful—skin biopsy, autonomic function testing—and we identified the blood tests that were most likely to provide supportive evidence—four specific blood tests associated with dysimmunity. Having a specific diagnosis to test for and treat when present may reduce ineffective, costly, and potentially harmful tests and treatments and permit objective testing and definitive treatment of some patients.”

In addition, the researchers said their results “demonstrate the need for pediatric norms for tests of SFPN, and they provide new testable hypotheses for clinical and basic research study that we are now engaged in.”

—Glenn S. Williams
Vice President, Group Editor

Suggested Reading
Oaklander AL, Klein MM. Evidence of small-fiber polyneuropathy in unexplained, juvenile-onset, widespread pain syndromes. Pediatrics. 2013;131(4):e1091-1100. 

Depression in late life can accelerate cognitive decline. A new study shows that depression in older adults significantly increased the risk of all-cause dementia, Alzheimer’s disease, and vascular dementia.

Depression after age 50 increased the risk of all-cause dementia by 1.85 times, Alzheimer’s disease by 1.65 times, and vascular dementia by 2.52 times, according to the results of a study published in the May issue of the British Journal of Psychiatry.

The meta-analysis, conducted by Dr. Breno S. Diniz and his associates at Western Psychiatric Institute and Clinic at the University of Pittsburgh Medical Center, is the first of its kind to examine both the risk of Alzheimer’s disease and vascular dementia in older adults with depression. Alzheimer’s disease is the most common form of dementia, followed by vascular dementia, which is characterized by impaired judgment or an inability to plan and complete tasks.

Dr. Diniz and his colleagues said their study also distinguished itself in another way. "This is the first study to show that late-life depression increases the risk of vascular dementia, and that the risk of vascular dementia is greater than the risk of Alzheimer’s disease for older adults with depression," they wrote.

A meta-analysis of 23 prospective community-based cohort studies was conducted to calculate the pooled risk of all-cause dementia, Alzheimer’s disease, and vascular dementia. Only studies with baseline cases of depression in adults aged 50 years or older were included. Data from 49,612 participants were used for the pooled analysis for all-cause dementia; 28,746 participants were included in the pooled analysis for Alzheimer’s disease; and 14,901 participants were included in the pooled analysis for vascular dementia. The median follow-up interval for all-cause dementia studies was 5 years. For Alzheimer’s disease studies, the median follow-up interval was 5 years and for vascular dementia studies, it was 6.1 years (Br. J. Psychiatry 2013;202:329-335).

After excluding studies that did not report risk measures adjusted for multiple confounders, a reduced, although statistically significant, association was found between late-life depression and the risk of all-cause dementia, Alzheimer’s disease, and vascular dementia. The adjusted pooled risk for all-cause dementia was 1.59 and 1.55 for Alzheimer’s. For vascular dementia, the adjusted pooled risk was 2.02, with a confidence interval of 95%.

They said their results were in line with a report showing an increased risk of all three conditions among participants with mid- and late-life depression. These findings came from a retrospective analysis of 13,535 older participants who were followed on the Kaiser Permanente Medical Care Program of Northern California (Arch. Gen. Psychiatry 2012;69:493-498).

In the current meta-analysis, the researchers recommended conducting new clinical trials to investigate the potential impact of depression prevention on the risk of cognitive impairment and dementia among older adults.

"Also, the prevention and treatment of cardiovascular risk factors and an improvement of general health in people with late-life depression may have a significant impact not only in a reduction of late-life depression cases but also [in the] reduction of dementia cases (vascular dementia and Alzheimer’s disease) associated with this disorder," the authors commented.

The researchers cited several limitations. Among them is that their meta-analysis was limited to PubMed and Scopus databases. A search of international databases such as EMBASE and PsychINFO might have led to additional studies, but they believe that their literature search was comprehensive.

—Christine Lehmann
IMNG Medical News

Depression in late life can accelerate cognitive decline. A new study shows that depression in older adults significantly increased the risk of all-cause dementia, Alzheimer’s disease, and vascular dementia.

Depression after age 50 increased the risk of all-cause dementia by 1.85 times, Alzheimer’s disease by 1.65 times, and vascular dementia by 2.52 times, according to the results of a study published in the May issue of the British Journal of Psychiatry.

The meta-analysis, conducted by Dr. Breno S. Diniz and his associates at Western Psychiatric Institute and Clinic at the University of Pittsburgh Medical Center, is the first of its kind to examine both the risk of Alzheimer’s disease and vascular dementia in older adults with depression. Alzheimer’s disease is the most common form of dementia, followed by vascular dementia, which is characterized by impaired judgment or an inability to plan and complete tasks.

Dr. Diniz and his colleagues said their study also distinguished itself in another way. "This is the first study to show that late-life depression increases the risk of vascular dementia, and that the risk of vascular dementia is greater than the risk of Alzheimer’s disease for older adults with depression," they wrote.

A meta-analysis of 23 prospective community-based cohort studies was conducted to calculate the pooled risk of all-cause dementia, Alzheimer’s disease, and vascular dementia. Only studies with baseline cases of depression in adults aged 50 years or older were included. Data from 49,612 participants were used for the pooled analysis for all-cause dementia; 28,746 participants were included in the pooled analysis for Alzheimer’s disease; and 14,901 participants were included in the pooled analysis for vascular dementia. The median follow-up interval for all-cause dementia studies was 5 years. For Alzheimer’s disease studies, the median follow-up interval was 5 years and for vascular dementia studies, it was 6.1 years (Br. J. Psychiatry 2013;202:329-335).

After excluding studies that did not report risk measures adjusted for multiple confounders, a reduced, although statistically significant, association was found between late-life depression and the risk of all-cause dementia, Alzheimer’s disease, and vascular dementia. The adjusted pooled risk for all-cause dementia was 1.59 and 1.55 for Alzheimer’s. For vascular dementia, the adjusted pooled risk was 2.02, with a confidence interval of 95%.

They said their results were in line with a report showing an increased risk of all three conditions among participants with mid- and late-life depression. These findings came from a retrospective analysis of 13,535 older participants who were followed on the Kaiser Permanente Medical Care Program of Northern California (Arch. Gen. Psychiatry 2012;69:493-498).

In the current meta-analysis, the researchers recommended conducting new clinical trials to investigate the potential impact of depression prevention on the risk of cognitive impairment and dementia among older adults.

"Also, the prevention and treatment of cardiovascular risk factors and an improvement of general health in people with late-life depression may have a significant impact not only in a reduction of late-life depression cases but also [in the] reduction of dementia cases (vascular dementia and Alzheimer’s disease) associated with this disorder," the authors commented.

The researchers cited several limitations. Among them is that their meta-analysis was limited to PubMed and Scopus databases. A search of international databases such as EMBASE and PsychINFO might have led to additional studies, but they believe that their literature search was comprehensive.

—Christine Lehmann
IMNG Medical News

Depression in late life can accelerate cognitive decline. A new study shows that depression in older adults significantly increased the risk of all-cause dementia, Alzheimer’s disease, and vascular dementia.

Depression after age 50 increased the risk of all-cause dementia by 1.85 times, Alzheimer’s disease by 1.65 times, and vascular dementia by 2.52 times, according to the results of a study published in the May issue of the British Journal of Psychiatry.

The meta-analysis, conducted by Dr. Breno S. Diniz and his associates at Western Psychiatric Institute and Clinic at the University of Pittsburgh Medical Center, is the first of its kind to examine both the risk of Alzheimer’s disease and vascular dementia in older adults with depression. Alzheimer’s disease is the most common form of dementia, followed by vascular dementia, which is characterized by impaired judgment or an inability to plan and complete tasks.

Dr. Diniz and his colleagues said their study also distinguished itself in another way. "This is the first study to show that late-life depression increases the risk of vascular dementia, and that the risk of vascular dementia is greater than the risk of Alzheimer’s disease for older adults with depression," they wrote.

A meta-analysis of 23 prospective community-based cohort studies was conducted to calculate the pooled risk of all-cause dementia, Alzheimer’s disease, and vascular dementia. Only studies with baseline cases of depression in adults aged 50 years or older were included. Data from 49,612 participants were used for the pooled analysis for all-cause dementia; 28,746 participants were included in the pooled analysis for Alzheimer’s disease; and 14,901 participants were included in the pooled analysis for vascular dementia. The median follow-up interval for all-cause dementia studies was 5 years. For Alzheimer’s disease studies, the median follow-up interval was 5 years and for vascular dementia studies, it was 6.1 years (Br. J. Psychiatry 2013;202:329-335).

After excluding studies that did not report risk measures adjusted for multiple confounders, a reduced, although statistically significant, association was found between late-life depression and the risk of all-cause dementia, Alzheimer’s disease, and vascular dementia. The adjusted pooled risk for all-cause dementia was 1.59 and 1.55 for Alzheimer’s. For vascular dementia, the adjusted pooled risk was 2.02, with a confidence interval of 95%.

They said their results were in line with a report showing an increased risk of all three conditions among participants with mid- and late-life depression. These findings came from a retrospective analysis of 13,535 older participants who were followed on the Kaiser Permanente Medical Care Program of Northern California (Arch. Gen. Psychiatry 2012;69:493-498).

In the current meta-analysis, the researchers recommended conducting new clinical trials to investigate the potential impact of depression prevention on the risk of cognitive impairment and dementia among older adults.

"Also, the prevention and treatment of cardiovascular risk factors and an improvement of general health in people with late-life depression may have a significant impact not only in a reduction of late-life depression cases but also [in the] reduction of dementia cases (vascular dementia and Alzheimer’s disease) associated with this disorder," the authors commented.

The researchers cited several limitations. Among them is that their meta-analysis was limited to PubMed and Scopus databases. A search of international databases such as EMBASE and PsychINFO might have led to additional studies, but they believe that their literature search was comprehensive.

—Christine Lehmann
IMNG Medical News

LONDON—Intermittent pneumatic compression (IPC) may reduce the absolute risk of proximal deep vein thrombosis (DVT) by 3.6% in patients who have had a stroke and are immobile, according to findings presented at the 2013 European Stroke Conference and published online ahead of print May 31 in Lancet.

The incidence of proximal DVT at 30 days in the CLOTS 3 study (a large, randomized trial) was 8.5% with IPC and 12.1% with routine poststroke care alone. In addition, the risk of death at six months was 14% lower among patients who received IPC than among patients who received routine care alone. This finding was surprising, said principal investigator Martin Dennis, MD, Professor of Stroke Medicine at the University of Edinburgh’s Division of Clinical Neurosciences. IPC appears to be effective in various prespecified subgroups, including for ischemic and hemorrhagic stroke.

Comparing ICP With Routine Care
CLOTS 3 was the most recent trial performed by the Clots in Legs or Stockings after Stroke (CLOTS) Trials Collaboration. In the trials, researchers examined compression stockings as a possible means of preventing thrombotic complications in patients with stroke. Compression stockings had no benefit for patients with stroke in CLOTS 1 and CLOTS 2.

Between December 2008 and September 2012, a total of 2,876 immobile patients with stroke were enrolled in CLOTS 3. Immobility was defined as the inability to walk to the bathroom without the help of another person.

Patients were randomized within three days of stroke onset to receive either routine poststroke care alone or routine poststroke care with IPC delivered by Covidien’s Kendall SCD Express Sequential Compression System. The latter involved wearing thigh-high, inflatable sleeves continuously for as many as 30 days, during which time the device automatically provided IPC, depending on the patient’s position. The mean and median durations of wear were 12.5 days and 9.0 days, respectively.

DVT was assessed using duplex ultrasound at seven to 10 days and again at 25 to 30 days if possible. Both patient groups wore compression sleeves to ensure that the ultrasound technicians remained blinded to the treatment group. Follow-up was conducted at six months through questionnaires mailed to patients’ primary care physicians. The questionnaires solicited information about patients’ vital status and the occurrence of venous thromboembolism since hospital discharge. Patients also received a questionnaire by mail and were telephoned if they did not respond.

IPC Was Relatively Safe
The effect on proximal DVT at 30 days was the primary outcome measure. Compared with routine care, IPC reduced the incidence of symptomatic DVT (6.3% vs. 4.6%) and any DVT (21.1% vs. 16.2%). Investigators observed no significant difference in the incidence of pulmonary embolism between study arms.

There was no difference between the treatment groups in the number of falls with injury or fractures as a result of constantly wearing the compression sleeves. The researchers observed a significant difference in skin ulcers (3.1% with IPC vs 1.4% without), but close inspection of the data suggested that 10 (0.7%) cases resulted from IPC.

“During the study, [the manufacturers of the IPC device] brought out a new comfort sleeve,” Dr. Dennis noted. “Normally, these sleeves were being used for short periods in surgical patients, but we were using them for longer periods, so they brought out a softer sleeve.” Some patients found the sleeves uncomfortable or too hot, and others described the system as “noisy,” added Dr. Dennis.

Nevertheless, “IPC in people who are immobile with stroke reduces the risk of DVT,” said Dr. Dennis. “IPC is feasible in stroke patients, and it is relatively safe. It is an effective means of reducing venous thromboembolism after stroke, with a number needed to treat of about 28 for proximal DVT.”

IPC may also improve overall survival, “although we weren’t expecting to see that effect,” said Dr. Dennis. The number needed to treat to prevent one death in 30 days was 43.

Findings Could Change Clinical Practice
“This study is a major breakthrough, showing how a simple and safe treatment can save lives,” said Anthony Rudd, MD, a consultant stroke physician at Guy’s and St. Thomas’ NHS Foundation Trust in London. “The challenge now will be to ensure that all patients who might benefit are offered treatment,” added Dr. Rudd, who chairs the Royal College of Physicians’ Intercollegiate Stroke Working Party. “It is one of the most important research studies to emerge in the field of stroke in recent years.”

“That something as simple as a compressive sleeve saves lives after stroke is fascinating,” said Christine Roffe, MD, consultant in stroke medicine and Professor of Medicine at Keele University in Stoke-on-Trent, UK. Dr. Roffe was not involved in the study.

—Sara Freeman
IMNG Medical News

Suggested Reading

CLOTS (Clots in Legs Or sTockings after Stroke) Trials Collaboration. Effectiveness of intermittent pneumatic compression in reduction of risk of deep vein thrombosis in patients who have had a stroke (CLOTS 3): a multicentre randomised controlled trial. Lancet. 2013 May 30 [Epub ahead of print].

CLOTS Trials Collaboration, Dennis M, Sandercock P, et al. The effect of graduated compression stockings on long-term outcomes after stroke: the CLOTS trials 1 and 2. Stroke. 2013;44(4):1075-1079.

Turpie AG, Hull RD, Schellong SM, et al. Venous thromboembolism risk in ischemic stroke patients receiving extended-duration enoxaparin prophylaxis: results from the EXCLAIM study. Stroke. 2013;44(1):249-251.

LONDON—Intermittent pneumatic compression (IPC) may reduce the absolute risk of proximal deep vein thrombosis (DVT) by 3.6% in patients who have had a stroke and are immobile, according to findings presented at the 2013 European Stroke Conference and published online ahead of print May 31 in Lancet.

The incidence of proximal DVT at 30 days in the CLOTS 3 study (a large, randomized trial) was 8.5% with IPC and 12.1% with routine poststroke care alone. In addition, the risk of death at six months was 14% lower among patients who received IPC than among patients who received routine care alone. This finding was surprising, said principal investigator Martin Dennis, MD, Professor of Stroke Medicine at the University of Edinburgh’s Division of Clinical Neurosciences. IPC appears to be effective in various prespecified subgroups, including for ischemic and hemorrhagic stroke.

Comparing ICP With Routine Care
CLOTS 3 was the most recent trial performed by the Clots in Legs or Stockings after Stroke (CLOTS) Trials Collaboration. In the trials, researchers examined compression stockings as a possible means of preventing thrombotic complications in patients with stroke. Compression stockings had no benefit for patients with stroke in CLOTS 1 and CLOTS 2.

Between December 2008 and September 2012, a total of 2,876 immobile patients with stroke were enrolled in CLOTS 3. Immobility was defined as the inability to walk to the bathroom without the help of another person.

Patients were randomized within three days of stroke onset to receive either routine poststroke care alone or routine poststroke care with IPC delivered by Covidien’s Kendall SCD Express Sequential Compression System. The latter involved wearing thigh-high, inflatable sleeves continuously for as many as 30 days, during which time the device automatically provided IPC, depending on the patient’s position. The mean and median durations of wear were 12.5 days and 9.0 days, respectively.

DVT was assessed using duplex ultrasound at seven to 10 days and again at 25 to 30 days if possible. Both patient groups wore compression sleeves to ensure that the ultrasound technicians remained blinded to the treatment group. Follow-up was conducted at six months through questionnaires mailed to patients’ primary care physicians. The questionnaires solicited information about patients’ vital status and the occurrence of venous thromboembolism since hospital discharge. Patients also received a questionnaire by mail and were telephoned if they did not respond.

IPC Was Relatively Safe
The effect on proximal DVT at 30 days was the primary outcome measure. Compared with routine care, IPC reduced the incidence of symptomatic DVT (6.3% vs. 4.6%) and any DVT (21.1% vs. 16.2%). Investigators observed no significant difference in the incidence of pulmonary embolism between study arms.

There was no difference between the treatment groups in the number of falls with injury or fractures as a result of constantly wearing the compression sleeves. The researchers observed a significant difference in skin ulcers (3.1% with IPC vs 1.4% without), but close inspection of the data suggested that 10 (0.7%) cases resulted from IPC.

“During the study, [the manufacturers of the IPC device] brought out a new comfort sleeve,” Dr. Dennis noted. “Normally, these sleeves were being used for short periods in surgical patients, but we were using them for longer periods, so they brought out a softer sleeve.” Some patients found the sleeves uncomfortable or too hot, and others described the system as “noisy,” added Dr. Dennis.

Nevertheless, “IPC in people who are immobile with stroke reduces the risk of DVT,” said Dr. Dennis. “IPC is feasible in stroke patients, and it is relatively safe. It is an effective means of reducing venous thromboembolism after stroke, with a number needed to treat of about 28 for proximal DVT.”

IPC may also improve overall survival, “although we weren’t expecting to see that effect,” said Dr. Dennis. The number needed to treat to prevent one death in 30 days was 43.

Findings Could Change Clinical Practice
“This study is a major breakthrough, showing how a simple and safe treatment can save lives,” said Anthony Rudd, MD, a consultant stroke physician at Guy’s and St. Thomas’ NHS Foundation Trust in London. “The challenge now will be to ensure that all patients who might benefit are offered treatment,” added Dr. Rudd, who chairs the Royal College of Physicians’ Intercollegiate Stroke Working Party. “It is one of the most important research studies to emerge in the field of stroke in recent years.”

“That something as simple as a compressive sleeve saves lives after stroke is fascinating,” said Christine Roffe, MD, consultant in stroke medicine and Professor of Medicine at Keele University in Stoke-on-Trent, UK. Dr. Roffe was not involved in the study.

—Sara Freeman
IMNG Medical News

Suggested Reading

CLOTS (Clots in Legs Or sTockings after Stroke) Trials Collaboration. Effectiveness of intermittent pneumatic compression in reduction of risk of deep vein thrombosis in patients who have had a stroke (CLOTS 3): a multicentre randomised controlled trial. Lancet. 2013 May 30 [Epub ahead of print].

CLOTS Trials Collaboration, Dennis M, Sandercock P, et al. The effect of graduated compression stockings on long-term outcomes after stroke: the CLOTS trials 1 and 2. Stroke. 2013;44(4):1075-1079.

Turpie AG, Hull RD, Schellong SM, et al. Venous thromboembolism risk in ischemic stroke patients receiving extended-duration enoxaparin prophylaxis: results from the EXCLAIM study. Stroke. 2013;44(1):249-251.

LONDON—Intermittent pneumatic compression (IPC) may reduce the absolute risk of proximal deep vein thrombosis (DVT) by 3.6% in patients who have had a stroke and are immobile, according to findings presented at the 2013 European Stroke Conference and published online ahead of print May 31 in Lancet.

The incidence of proximal DVT at 30 days in the CLOTS 3 study (a large, randomized trial) was 8.5% with IPC and 12.1% with routine poststroke care alone. In addition, the risk of death at six months was 14% lower among patients who received IPC than among patients who received routine care alone. This finding was surprising, said principal investigator Martin Dennis, MD, Professor of Stroke Medicine at the University of Edinburgh’s Division of Clinical Neurosciences. IPC appears to be effective in various prespecified subgroups, including for ischemic and hemorrhagic stroke.

Comparing ICP With Routine Care
CLOTS 3 was the most recent trial performed by the Clots in Legs or Stockings after Stroke (CLOTS) Trials Collaboration. In the trials, researchers examined compression stockings as a possible means of preventing thrombotic complications in patients with stroke. Compression stockings had no benefit for patients with stroke in CLOTS 1 and CLOTS 2.

Between December 2008 and September 2012, a total of 2,876 immobile patients with stroke were enrolled in CLOTS 3. Immobility was defined as the inability to walk to the bathroom without the help of another person.

Patients were randomized within three days of stroke onset to receive either routine poststroke care alone or routine poststroke care with IPC delivered by Covidien’s Kendall SCD Express Sequential Compression System. The latter involved wearing thigh-high, inflatable sleeves continuously for as many as 30 days, during which time the device automatically provided IPC, depending on the patient’s position. The mean and median durations of wear were 12.5 days and 9.0 days, respectively.

DVT was assessed using duplex ultrasound at seven to 10 days and again at 25 to 30 days if possible. Both patient groups wore compression sleeves to ensure that the ultrasound technicians remained blinded to the treatment group. Follow-up was conducted at six months through questionnaires mailed to patients’ primary care physicians. The questionnaires solicited information about patients’ vital status and the occurrence of venous thromboembolism since hospital discharge. Patients also received a questionnaire by mail and were telephoned if they did not respond.

IPC Was Relatively Safe
The effect on proximal DVT at 30 days was the primary outcome measure. Compared with routine care, IPC reduced the incidence of symptomatic DVT (6.3% vs. 4.6%) and any DVT (21.1% vs. 16.2%). Investigators observed no significant difference in the incidence of pulmonary embolism between study arms.

There was no difference between the treatment groups in the number of falls with injury or fractures as a result of constantly wearing the compression sleeves. The researchers observed a significant difference in skin ulcers (3.1% with IPC vs 1.4% without), but close inspection of the data suggested that 10 (0.7%) cases resulted from IPC.

“During the study, [the manufacturers of the IPC device] brought out a new comfort sleeve,” Dr. Dennis noted. “Normally, these sleeves were being used for short periods in surgical patients, but we were using them for longer periods, so they brought out a softer sleeve.” Some patients found the sleeves uncomfortable or too hot, and others described the system as “noisy,” added Dr. Dennis.

Nevertheless, “IPC in people who are immobile with stroke reduces the risk of DVT,” said Dr. Dennis. “IPC is feasible in stroke patients, and it is relatively safe. It is an effective means of reducing venous thromboembolism after stroke, with a number needed to treat of about 28 for proximal DVT.”

IPC may also improve overall survival, “although we weren’t expecting to see that effect,” said Dr. Dennis. The number needed to treat to prevent one death in 30 days was 43.

Findings Could Change Clinical Practice
“This study is a major breakthrough, showing how a simple and safe treatment can save lives,” said Anthony Rudd, MD, a consultant stroke physician at Guy’s and St. Thomas’ NHS Foundation Trust in London. “The challenge now will be to ensure that all patients who might benefit are offered treatment,” added Dr. Rudd, who chairs the Royal College of Physicians’ Intercollegiate Stroke Working Party. “It is one of the most important research studies to emerge in the field of stroke in recent years.”

“That something as simple as a compressive sleeve saves lives after stroke is fascinating,” said Christine Roffe, MD, consultant in stroke medicine and Professor of Medicine at Keele University in Stoke-on-Trent, UK. Dr. Roffe was not involved in the study.

—Sara Freeman
IMNG Medical News

Suggested Reading

CLOTS (Clots in Legs Or sTockings after Stroke) Trials Collaboration. Effectiveness of intermittent pneumatic compression in reduction of risk of deep vein thrombosis in patients who have had a stroke (CLOTS 3): a multicentre randomised controlled trial. Lancet. 2013 May 30 [Epub ahead of print].

CLOTS Trials Collaboration, Dennis M, Sandercock P, et al. The effect of graduated compression stockings on long-term outcomes after stroke: the CLOTS trials 1 and 2. Stroke. 2013;44(4):1075-1079.

Turpie AG, Hull RD, Schellong SM, et al. Venous thromboembolism risk in ischemic stroke patients receiving extended-duration enoxaparin prophylaxis: results from the EXCLAIM study. Stroke. 2013;44(1):249-251.

Pain in multiple sclerosis (MS) is common, occurring in 63% of patients with the disease, researchers reported in the May issue of Pain. Headache and extremity neuropathic pain are the most common pain syndromes in patients with MS.

Peter Foley, MRCP, and colleagues based their findings on a systematic review and meta-analysis of 17 prospective studies (5,319 patients) that explored pain prevalence in definite MS. The percentage of females in the studies ranged from 55% to 96%, mean age ranged from 31 to 54, mean disease duration ranged from 2.5 to 23 years, and between 30% and 100% of subjects had relapsing-remitting MS (RRMS).

The researchers found a pooled overall pain prevalence of 62.8%. They quantified a prevalence of 43% for headache, 26% for extremity neuropathic pain, 20% for back pain, 15% for painful spasms, 16% for painful Lhermitte sign, and 3.8% for trigeminal neuralgia. The prevalence of pain at MS disease milestones—prior to onset, at onset, and at relapse—and during longitudinal follow-up was “poorly described,” according to Dr. Foley, from the Division of Clinical Neurosciences, University of Edinburgh.

Among the studies that were reviewed, one investigated pain prevalence soon after MS diagnosis and found a 73.5% prevalence of any pain, with a mean disease duration at assessment of 30.5 months. A separate study analyzed headache during relapse and found a prevalence of 38.9%. In addition, two studies prospectively examined overall pain evolution with disease progression—one study found a nonsignificant reduction in prevalence of pain over time in early MS, while another found an increasing prevalence of pain over time in later MS, particularly in those with worsening disability.

“Pain seems to affect approximately 63% of people with MS,” Dr. Foley told Neurology Reviews. “People with MS suffer from a complex variety of pain problems, with both neuropathic and nociceptive mechanisms, and we now have a clearer idea of how common these different pain problems are in MS. Looking at pain overall in these studies, although there was significant variability between studies, we didn’t find that patient disability scores, disease duration, gender mix, or mix of people with progressive MS and RRMS in the studies significantly affected the prevalence of pain.

“Because pain is so common, and seems to affect all groups of people with MS, doctors should strongly consider asking their patients about pain,” Dr. Foley concluded. “Future research studies using standardized designs might give us further evidence to identify who is most at risk of pain, and how this might relate to inflammatory, degenerative, or other processes in MS.”

—Colby Stong
Editor

Suggested Reading
Foley PL, Vesterinen HM, Laird BJ, et al. Prevalence and natural history of pain in adults with multiple sclerosis: systematic review and meta-analysis. Pain. 2013;154(5):632-642.

Pain in multiple sclerosis (MS) is common, occurring in 63% of patients with the disease, researchers reported in the May issue of Pain. Headache and extremity neuropathic pain are the most common pain syndromes in patients with MS.

Peter Foley, MRCP, and colleagues based their findings on a systematic review and meta-analysis of 17 prospective studies (5,319 patients) that explored pain prevalence in definite MS. The percentage of females in the studies ranged from 55% to 96%, mean age ranged from 31 to 54, mean disease duration ranged from 2.5 to 23 years, and between 30% and 100% of subjects had relapsing-remitting MS (RRMS).

The researchers found a pooled overall pain prevalence of 62.8%. They quantified a prevalence of 43% for headache, 26% for extremity neuropathic pain, 20% for back pain, 15% for painful spasms, 16% for painful Lhermitte sign, and 3.8% for trigeminal neuralgia. The prevalence of pain at MS disease milestones—prior to onset, at onset, and at relapse—and during longitudinal follow-up was “poorly described,” according to Dr. Foley, from the Division of Clinical Neurosciences, University of Edinburgh.

Among the studies that were reviewed, one investigated pain prevalence soon after MS diagnosis and found a 73.5% prevalence of any pain, with a mean disease duration at assessment of 30.5 months. A separate study analyzed headache during relapse and found a prevalence of 38.9%. In addition, two studies prospectively examined overall pain evolution with disease progression—one study found a nonsignificant reduction in prevalence of pain over time in early MS, while another found an increasing prevalence of pain over time in later MS, particularly in those with worsening disability.

“Pain seems to affect approximately 63% of people with MS,” Dr. Foley told Neurology Reviews. “People with MS suffer from a complex variety of pain problems, with both neuropathic and nociceptive mechanisms, and we now have a clearer idea of how common these different pain problems are in MS. Looking at pain overall in these studies, although there was significant variability between studies, we didn’t find that patient disability scores, disease duration, gender mix, or mix of people with progressive MS and RRMS in the studies significantly affected the prevalence of pain.

“Because pain is so common, and seems to affect all groups of people with MS, doctors should strongly consider asking their patients about pain,” Dr. Foley concluded. “Future research studies using standardized designs might give us further evidence to identify who is most at risk of pain, and how this might relate to inflammatory, degenerative, or other processes in MS.”

—Colby Stong
Editor

Suggested Reading
Foley PL, Vesterinen HM, Laird BJ, et al. Prevalence and natural history of pain in adults with multiple sclerosis: systematic review and meta-analysis. Pain. 2013;154(5):632-642.

Pain in multiple sclerosis (MS) is common, occurring in 63% of patients with the disease, researchers reported in the May issue of Pain. Headache and extremity neuropathic pain are the most common pain syndromes in patients with MS.

Peter Foley, MRCP, and colleagues based their findings on a systematic review and meta-analysis of 17 prospective studies (5,319 patients) that explored pain prevalence in definite MS. The percentage of females in the studies ranged from 55% to 96%, mean age ranged from 31 to 54, mean disease duration ranged from 2.5 to 23 years, and between 30% and 100% of subjects had relapsing-remitting MS (RRMS).

The researchers found a pooled overall pain prevalence of 62.8%. They quantified a prevalence of 43% for headache, 26% for extremity neuropathic pain, 20% for back pain, 15% for painful spasms, 16% for painful Lhermitte sign, and 3.8% for trigeminal neuralgia. The prevalence of pain at MS disease milestones—prior to onset, at onset, and at relapse—and during longitudinal follow-up was “poorly described,” according to Dr. Foley, from the Division of Clinical Neurosciences, University of Edinburgh.

Among the studies that were reviewed, one investigated pain prevalence soon after MS diagnosis and found a 73.5% prevalence of any pain, with a mean disease duration at assessment of 30.5 months. A separate study analyzed headache during relapse and found a prevalence of 38.9%. In addition, two studies prospectively examined overall pain evolution with disease progression—one study found a nonsignificant reduction in prevalence of pain over time in early MS, while another found an increasing prevalence of pain over time in later MS, particularly in those with worsening disability.

“Pain seems to affect approximately 63% of people with MS,” Dr. Foley told Neurology Reviews. “People with MS suffer from a complex variety of pain problems, with both neuropathic and nociceptive mechanisms, and we now have a clearer idea of how common these different pain problems are in MS. Looking at pain overall in these studies, although there was significant variability between studies, we didn’t find that patient disability scores, disease duration, gender mix, or mix of people with progressive MS and RRMS in the studies significantly affected the prevalence of pain.

“Because pain is so common, and seems to affect all groups of people with MS, doctors should strongly consider asking their patients about pain,” Dr. Foley concluded. “Future research studies using standardized designs might give us further evidence to identify who is most at risk of pain, and how this might relate to inflammatory, degenerative, or other processes in MS.”

—Colby Stong
Editor

Suggested Reading
Foley PL, Vesterinen HM, Laird BJ, et al. Prevalence and natural history of pain in adults with multiple sclerosis: systematic review and meta-analysis. Pain. 2013;154(5):632-642.