New and Noteworthy Information—June 2013

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