JAMA Neurology Current Issue

A Mild Form of Adult-Onset Opsoclonus-Myoclonus Syndrome Associated With Antiglutamate Receptor Antibodies

Kambe T, Takahashi Y, Furukawa Y. — Wed, 01 May 2013 00:00:00 GMT

We read with interest the article by Klaas and colleagues on adult-onset opsoclonus-myoclonus syndrome (OMS). The authors reported the clinical characteristics of 21 patients at the Mayo Clinic and 116 patients in the literature, and they found 2 patients with adult-onset OMS associated with anti– N-methyl-D-aspartate receptor antibodies in their literature review. Initial symptoms of these 2 patients were behavioral and/or mood changes, and they developed severe encephalopathy.

A Mild Form of Adult-Onset Opsoclonus-Myoclonus Syndrome Associated With Antiglutamate Receptor Antibodies—Reply

McKeon A, Pittock S. — Wed, 01 May 2013 00:00:00 GMT

In reply

A Questionable Cause of Intracerebral Hemorrhage

Esenwa CC, Elkind MV. — Wed, 01 May 2013 00:00:00 GMT

In their recent article, Gokhale and colleagues described a man with a history of migraines who experienced an intracerebral hemorrhage (ICH). They claimed that this was an example of the amorphous entity termed migraine-associated ICH. However, the differential for an angiogram-negative lobar ICH is wide. It includes hypertensive hemorrhage, cerebral amyloid angiopathy, vascular malformation, aneurysmal rupture, cerebral vein thrombosis, coagulopathy, bleeding tumor, and drugs. There are also other genetic and lifestyle risk factors, of which migraine is not one. To our knowledge, there is in fact only 1 prospective study that supports the authors' conclusion. In the Women's Health Study, Kurth and colleagues found that women with a history of migraine with aura had an absolute risk increase of 0.003% (hazard ratio, 2.3) for ICH. Because of the low attributable risk, the authors explicitly acknowledged that the study did not provide definitive evidence of association. There is no evidence to support the diagnosis in men.

A Questionable Cause of Intracerebral Hemorrhage—Reply

Wed, 01 May 2013 00:00:00 GMT

In reply

About This Journal

Wed, 01 May 2013 00:00:00 GMT

Acute Unilateral Hearing Loss as an Early Symptom of Lateral Cerebral Sinus Venous Thrombosis

Gokhale S. — Wed, 01 May 2013 00:00:00 GMT

Gattringer et al reported an interesting observation about the association of lateral venous sinus thrombosis and unilateral hearing loss in a cohort of 3 patients in a recent issue of the journal.

Acute Unilateral Hearing Loss as an Early Symptom of Lateral Cerebral Sinus Venous Thrombosis—Reply

Gattringer T, Enzinger C, Fazekas F. — Wed, 01 May 2013 00:00:00 GMT

In reply

Bruns Nystagmus in Cerebellopontine Angle Tumor Bruns Nystagmus in Cerebellopontine Angle Tumor

Venkateswaran R, Gupta R, Swaminathan R. — Wed, 01 May 2013 00:00:00 GMT

A 35-year-old woman presented with insidious onset of hearing loss on the left side along with progressive unsteadiness of gait and diminution of vision. She had features of increased intracranial pressure. Clinical examination revealed gross papilledema in both eyes with secondary optic atrophy. A right-sided lower motor neuron type of facial palsy was present. Corneal reflex was absent on the right side. Eye movements were full. A coarse right-beating nystagmus with rightward gaze and a fine primary-position left-beating nystagmus (which was appreciated by ophthalmoscopy) that increased on leftward gaze, consistent with Bruns nystagmus, was noticed (video). Hence, a space-occupying lesion in the right cerebellopontine angle was considered.

Can Mild Cognitive Impairment in Parkinson Disease Predict the Development of Dementia? MCI in PD and the Development of Dementia

Copeland BJ, Schiess MC. — Wed, 01 May 2013 00:00:00 GMT

The term mild cognitive impairment (MCI) emerged in the 1990s, defining a transition state from normal cognitive function and forcing our appreciation of cognitive changes not attributable to age, education, sex, race, ethnicity, language, or culture, but rather to a well-defined disease process or related pathology. The acceptance of MCI as a precursor to dementia and its use in predicting progression to Alzheimer dementia, by identifying a profile of cognitive dysfunction unique to Alzheimer dementia and attributable to the disease process and related pathology, is well substantiated. Recently, subtypes of MCI have been described that may have individual predilections for various dementia types.

Central Veins in Brain Lesions Visualized With High-Field Magnetic Resonance Imaging A Pathologically Specific Diagnostic Biomarker for Inflammatory Demyelination in the Brain Central Veins in Brain Lesions Visualized With MRI

Mistry N, Dixon J, Tallantyre E, et al. — Wed, 01 May 2013 00:00:00 GMT

Importance

There is no single test that is diagnostic for multiple sclerosis (MS), and existing diagnostic criteria are imperfect. This can lead to diagnostic delay. Some patients require multiple (sometimes invasive) investigations, and extensive clinical follow-up to confirm or exclude a diagnosis of MS. A diagnostic biomarker that is pathologically specific for the inflammatory demyelination in MS could overhaul current diagnostic algorithms.

Objective

To prospectively assess the diagnostic value of visualizing central veins in brain lesions with magnetic resonance imaging (MRI) for patients with possible MS for whom the diagnosis is uncertain.

Design

Prospective longitudinal cohort study. The reference standard is a clinical diagnosis that is arrived at (after a mean follow-up of 26 months) by the treating neurologist with a specialist interest in MS. The 7-T MRI scans were analyzed at baseline, by physicians blinded to the clinical data, for the presence of visible central veins.

Setting

Academic MS referral center.

Participants

A consecutive sample of 29 patients referred with possible MS who had brain lesions detected on clinical MRI scans but whose condition remained undiagnosed despite expert clinical and radiological assessments.

Exposure

Seven-Tesla MRI using a T2*-weighted sequence.

Main Outcomes and Measures

The proportion of patients whose condition was correctly diagnosed as MS or as not MS, using 7-T MRI at study onset, compared with the eventual diagnosis reached by treating physicians blinded to the result of the MRI scan.

Results

Of the 29 patients enrolled and scanned using 7-T MRI, so far 22 have received a clinical diagnosis. All 13 patients whose condition was eventually diagnosed as MS had central veins visible in the majority of brain lesions at baseline. All 9 patients whose condition was eventually not diagnosed as MS had central veins visible in a minority of lesions.

Conclusions and Relevance

In our study, T2*-weighted 7-T MRI had 100% positive and negative predictive value for the diagnosis of MS. Clinical application of this technique could improve existing diagnostic algorithms.

Correlation of Specific Amyloid-β Oligomers With Tau in Cerebrospinal Fluid From Cognitively Normal Older Adults Aβ Oligomers and Tau in CSF From Normal Adults

Handoko M, Grant M, Kuskowski M, et al. — Wed, 01 May 2013 00:00:00 GMT

Importance

To improve the ability to develop treatments that prevent incipient Alzheimer disease (AD) from progressing to overt AD, it is important to understand the molecular basis of the earliest pathophysiological abnormalities and to determine how amyloid-β (Aβ) is involved very early in its pathogenesis.

Objective

To investigate 2 specific Aβ oligomers, Aβ trimers and Aβ*56, in human cerebrospinal fluid (CSF); evaluate the effects of aging and AD; and obtain support for the hypothesis that they may be pathogenic by determining their relationships to CSF tau.

Design

A CSF sampling study.

Settings

The University of Minnesota Medical School in Minneapolis, Minnesota, and the Salhgrenska University Hospital, Sweden.

Participants

Forty-eight older adults with mild cognitive impairment or AD (impaired group); 49 age-matched cognitively intact control subjects (unimpaired group); and 10 younger, normal control subjects.

Main Outcome Measures

Measurements of CSF Aβ trimers, Aβ*56, the 42–amino acid Aβ isoform (Aβ1-42), total tau (T-tau), and phospho-tau 181 (p-tau₁₈₁). The hypothesis being tested was formulated after data collection.

Results

We observed that Aβ trimers and Aβ*56 levels increased with age; within the unimpaired group, they were elevated in subjects with T-tau/Aβ1-42 ratios greater than a cutoff that distinguished the unimpaired group from subjects with AD. In the unimpaired group, T-tau and p-tau₁₈₁ were found to correlate strongly with Aβ trimers and Aβ*56 (r > 0.63), but not with Aβ1-42 (−0.10 < r < −0.01). The strong correlations were found to be attenuated in the impaired group.

Conclusions and Relevance

In cognitively intact older adults, CSF Aβ trimers and Aβ*56 were elevated in individuals at risk for AD, and they showed stronger relationships with tau than did Aβ1-42, a surrogate for Aβ fibril deposition. These findings suggest that prior to overt symptoms, 1 or both of the Aβ oligomers, but not fibrillar Aβ, is coupled to tau; however, this coupling is weakened or broken when AD advances to symptomatic stages. The uncoupling is interesting in light of the failure of experimental Aβ therapies to improve mild cognitive impairment/AD, which has prompted a shift in the timing of Aβ therapies to asymptomatic subjects. Knowing which Aβ species to target in asymptomatic subjects may enhance the success of future treatments for AD.

Imaging Cortical Damage and Dysfunction in Multiple Sclerosis Imaging Cortical Damage and Dysfunction in MS

Filippi M, Rocca MA, Horsfield MA, et al. — Wed, 01 May 2013 00:00:00 GMT

In line with pathological investigations, in vivo magnetic resonance imaging has consistently shown both focal and diffuse damage in the cerebral cortex of patients with multiple sclerosis. Cortical injury tends to progress over time and is only partially related to white matter abnormalities. This review summarizes the main findings from studies using both conventional and modern quantitative magnetic resonance–based techniques for the assessment of cortical damage and dysfunction in patients with multiple sclerosis.

In This Issue of JAMA Neurology

Wed, 01 May 2013 00:00:00 GMT

Interferon Beta and Long-term Disability in Multiple Sclerosis

Shirani A, Zhao Y, Karim M, et al. — Wed, 01 May 2013 00:00:00 GMT

Greenberg et al highlighted our recent paper, which reported a “lack of evidence for a strong association between interferon beta treatment and disability progression.” This should not be interpreted as “interferon use does not prevent disability in patients with multiple sclerosis.” Nor does it seem appropriate to conclude that “the relapses prevented by interferon have been shown to lead to disability accumulation” by citing 2 short-term randomized clinical trials. It has become apparent that short-term effects may not translate into long-term benefits. This is consistent with the observation that the association between relapses and disability progression diminishes over time.

Interferon Beta and Long-term Disability in Multiple Sclerosis—Reply

Greenberg BM, Frohman E. — Wed, 01 May 2013 00:00:00 GMT

In reply

Intracerebral Hemorrhage Caused by Migraine

Sethi NK. — Wed, 01 May 2013 00:00:00 GMT

Gokhale et al reported the case of a 54-year-old man with left parietooccipital hemorrhage and hypothesized that it was likely caused by migraine. As the authors themselves pointed out, intracerebral hemorrhage due to migraine is exceedingly rare, with only a few cases reported in the literature. Critical review of these cases reveals that in all migraines as a cause of intracerebral hemorrhage, there was a diagnosis of exclusion. In the authors' reported case too there were a few inconsistencies that cause one to stop and ponder. First their patient's typical migraine headaches preceding the intracerebral hemorrhage were consistently lateralized to the left parietooccipital area. This is highly atypical for migraine episodes, which usually demonstrate shifting laterality. A vascular malformation, such as an arteriovenous malformation or an arterial-dural fistula causing the lobar hemorrhage and which was self-obliterated by the time of the catheter angiogram, is still a possibility. It may be prudent to repeat the angiogram after an interval of 3 to 6 months.

Isolated Central Nervous System Histoplasmosis Presenting With Ischemic Pontine Stroke and Meningitis in an Immune-Competent Patient Isolated Central Nervous System Histoplasmosis

Nguyen FN, Kar JK, Zakaria A, et al. — Wed, 01 May 2013 00:00:00 GMT

Importance

Histoplasmosis, a systemic mycosis caused by the fungus Histoplasma capsulatum, primarily affects immune-suppressed patients and commonly involves the lung and rarely the central nervous system (CNS). Herein, we report a case of isolated CNS histoplasmosis presenting with pontine stroke and meningitis.

Observations

A 35-year-old, white, immune-competent man was transferred from an outside facility with worsening dysarthria and confusion after having presented 4 weeks prior with dysarthria, gait ataxia, and bilateral upper extremity weakness. Brain magnetic resonance imaging revealed bilateral pontine strokes, and the working diagnosis was ischemic infarctions, presumed secondary to small vessel vasculitis. Cerebral spinal fluid (CSF) examination showed marked abnormalities including an elevated protein level (320 mg/dL), low glucose level (2 mg/dL), and high white blood cell count (330/mm³; 28% lymphocytes, 56% neutrophils, and 16% monocytes) suggestive of a bacterial, fungal, or tuberculosis meningitis. Empirical antibiotics and a second trial of intravenous steroids were started before infectious etiologies of meningitis were ultimately ruled out. Repeated magnetic resonance imaging of the brain revealed no evidence of new ischemic lesions. On hospital day 11, results of his CSF Histoplasma antigen and urine antigen tests were positive. His CSF culture also was positive for H capsulatum. The patient was treated initially with liposomal amphotericin B, 430 mg daily, but changed to voriconazole, 300 mg twice daily, secondary to renal insufficiency and eventually continued treatment with itraconazole cyclodextrin, 100 mg twice daily. Computed tomographic imaging revealed obstructive hydrocephalus, and a ventriculoperitoneal shunt was placed that successfully decompressed the ventricles. At 1 year, the patient demonstrated good clinical improvement and results of follow-up CSF cultures were negative.

Conclusions and Relevance

While pulmonary involvement of histoplasmosis in immune-suppressed patients is common, systemic presentation of this fungal infection in immune-competent patients is rare and self-limiting. Isolated CNS histoplasmosis is exceedingly rare. Clinicians should consider CNS histoplasmosis in the differential diagnosis in atypical stroke cases, particularly those presenting with meningitis.

Lessons for Parkinson Disease From the Parkin Genotype Lessons for PD From the Parkin Genotype

Ahlskog J. — Wed, 01 May 2013 00:00:00 GMT

Monogenetic forms of parkinsonism now include 16 established loci in the “ PARK ” nomenclature. In this issue of JAMA Neurology, Doherty and colleagues describe details of the most common autosomal recessive parkinsonism, PARK2, which is associated with parkin gene mutations. In the most comprehensive description of PARK2, these investigators detail the clinical phenotype of 5 patients, who were observed for decades, plus their neuropathology. Notably, the pathology was a non–Lewy body pathology. Although parkin is uncommon in Parkinson disease (PD) clinics, this report should be of interest to general neurologists once it is put into a broader context.

Metastatic Epidural Bacterial Abscess in a 4-Year-Old Boy Metastatic Epidural Bacterial Abscess

DeVries S. — Wed, 01 May 2013 00:00:00 GMT

A 4-year-old boy with community-acquired pneumonia unresponsive to outpatient antibiotics was admitted to the hospital for intravenous treatment. Chest computed tomography revealed left lower lobe pulmonary empyema (Figure 1), which led to the placement of a chest tube. After 1 week of intravenous antibiotics, the chest tube was removed and the patient was to be discharged home. Unexpectedly, the patient's clinical condition deteriorated. He became encephalopathic and had evidence of tonic eye deviation to the right. While undergoing an emergency computed tomographic scan of the head, the patient had a generalized tonic-clonic seizure. Head computed tomography revealed osteomyelitis of the left anterior, medial, and inferior frontal bone as well as left anterior, inferior, and medial epidural fluid collection suggestive of an epidural abscess. Brain magnetic resonance imaging with and without contrast confirmed the findings (Figure 2). The neurosurgeon performed an emergency hemicraniotomy and abscess evacuation; the surgical procedure was not associated with complications. Six months later, at a follow-up appointment, the patient had no evidence of neurological deficit.

Microcystic Inner Nuclear Layer Abnormalities and Neuromyelitis Optica Microcystic Inner Nuclear Layer and NMO

Gelfand JM, Cree BA, Nolan R, et al. — Wed, 01 May 2013 00:00:00 GMT

Importance

Microcystic abnormalities involving the inner nuclear layer of the retina occurs in a subset of patients with multiple sclerosis, most commonly in eyes previously affected by symptomatic optic neuritis. Acute optic neuritis is a cardinal manifestation of neuromyelitis optica (NMO). To our knowledge, microcystic inner nuclear layer abnormalities have not been investigated in NMO.

Objective

To establish whether microcystic inner nuclear layer abnormalities occur in NMO.

Design

Observational, retrospective study.

Setting

University of California at San Francisco Multiple Sclerosis Center (academic specialty clinic).

Patients

Twenty-five consecutive patients with NMO based on 2006 diagnostic criteria or with NMO spectrum disease (defined by seropositivity for anti–aquaporin 4 IgG in the context of a single episode of transverse myelitis or optic neuritis).

Exposure

Spectral-domain optical coherence tomography.

Main Outcomes and Measures

Identification of microcystic inner nuclear layer pathology on spectral-domain optical coherence tomography. Multivariable linear regression was used to examine associations between microcystic changes and measures of retinal structure and function. The hypothesis was generated prior to the data being reviewed and analyzed.

Results

Microcystic changes were identified in 5 of 25 patients with NMO (20%) and 7 of 48 total eyes, including 7 of 29 eyes (24%) previously affected by optic neuritis. Microcystic changes occurred exclusively in eyes with a history of acute symptomatic optic neuritis (100% of eyes with microcystic changes had experienced prior optic neuritis compared with 71% of NMO eyes without microcystic abnormalities). There were no significant differences between patients with NMO with and without microcystic changes in terms of age, sex, and aquaporin 4–IgG antibody status. The mean age in this cohort was 44 years (range, 13-81 years); 84% were women; 80% were aquaporin 4–IgG seropositive; and the median Expanded Disability Status Scale score was 4.0 (interquartile range, 3.0-6.5).

Conclusions and Relevance

Microcystic inner nuclear layer pathology occurs in a proportion of patients with NMO in eyes previously affected by acute optic neuritis. Additional research is needed to understand the cause of this retinal pathology and determine whether it contributes to persistent visual disability in patients with NMO following optic neuritis.

Neurogenetics: A Guide for Clinicians

Greenstein PE. — Wed, 01 May 2013 00:00:00 GMT

The role that genetics plays in clinical neurology continues to expand, and it is a daunting task to present this information to trainees and physicians, given the rapid pace at which this field is evolving. That being said, Professor Wood has put together a comprehensive book outlining important diseases with genetic etiologies in the field of clinical neurology. The topics covered include the genetics of Alzheimer disease, Huntington disease, parkinsonism, amyotrophic lateral sclerosis, inherited neuropathies, muscle dystrophies, mitochondrial disorders, the epilepsies, and neurocutaneous diseases.

Neuropathologic Basis of Age-Associated Brain Atrophy Neuropathology of Age-Associated Brain Atrophy

Erten-Lyons D, Dodge HH, Woltjer R, et al. — Wed, 01 May 2013 00:00:00 GMT

Importance

While brain volume changes are used as surrogate markers for Alzheimer disease neuropathology in clinical studies, the extent to which these changes are due to pathologic features of Alzheimer disease in the aging brain is not well established. This study aims to clarify the neuropathologic correlates of longitudinal brain atrophy.

Objective

To examine the association between brain atrophy during life and neuropathology in an elderly population.

Design

Autopsy study of a cohort of elderly individuals.

Setting

Community-based population.

Participants

Seventy-one healthy elderly individuals were selected from participants of the Oregon Brain Aging Study for having an autopsy, more than 1 magnetic resonance imaging scan, and the last magnetic resonance imaging scan within 36 months of death.

Main Outcomes and Measures

The associations between brain volume trajectories (ventricular, total brain, and hippocampal) and time interaction terms for neurofibrillary tangles, neuritic plaques, gross infarcts, microinfarcts, amyloid angiopathy, Lewy bodies, APOE ϵ4 presence, and clinical diagnosis (no cognitive impairment, mild cognitive impairment, or dementia as time-varying covariates) were examined in mixed-effects models, adjusting for duration of follow-up and age at death.

Results

Ventricular volume trajectory was significantly associated with age, presence of infarcts, neurofibrillary tangle and neuritic plaque scores, APOE ϵ4 allele presence, and dementia diagnosis. Total brain volume trajectory was significantly associated with age and mild cognitive impairment diagnosis. Hippocampal volume trajectory was significantly associated with amyloid angiopathy.

Conclusions and Relevance

Ventricular volume trajectory is more sensitive than total brain and hippocampal volume trajectories as a marker of accruing Alzheimer disease and vascular pathology in elderly individuals. The association between brain volume trajectories and cognitive impairment (mild cognitive impairment and dementia) remained after controlling for the degree of neuropathology and other covariates. This suggests that there may be other factors not measured in this study that could be contributing to brain atrophy in those with cognitive impairment.

Older vs Newer Antiepileptic Drugs: Is Old Still Gold?

Sethi NK. — Wed, 01 May 2013 00:00:00 GMT

I read with interest the results from the KONQUEST (Keppra vs Older AEDs evaluating Neuropsychiatric, Neurocognitive and QUality of life outcomes in treatment of Epilepsy as Substitution monoTherapy) trial. The trial showed no difference in quality of life, neuropsychiatric, neurocognitive, seizure control, and adverse event outcome measures when patients with partial epilepsy who had failed monotherapy with an older antiepileptic drug (AED) were switched to monotherapy with another older AED vs those switched to brand name levetiracetam (marketed in the United States as Keppra; UCB Pharma). The efficacy and adverse effect profile of an AED may vary between the brand name medication and its generic equivalents available on the market. Were the patients who were taking older AEDs switched to brand name older AEDs or their generic equivalents? This may have skewed the results reported. Patients who are well controlled with older AEDs are at times switched to newer generation AEDs on the grounds that they have a more favorable adverse effect profile in the long run, namely, lesser incidence of neurocognitive and neuropsychiatric adverse effects, bone loss, and safety during pregnancy. Results from the KONQUEST trial make us pause and ponder this rationale as newer AEDs, especially those that lack a generic equivalent, are far more expensive and place a significant financial burden both on the patient and society at large.

Older vs Newer Antiepileptic Drugs: Is Old Still Gold?—Reply

O’Brien TJ, Hakami T, Todaro M. — Wed, 01 May 2013 00:00:00 GMT

In reply

Parkin Disease A Clinicopathologic Entity? Parkin Disease

Doherty KM, Silveira-Moriyama L, Parkkinen L, et al. — Wed, 01 May 2013 00:00:00 GMT

Importance

Mutations in the gene encoding parkin (PARK2) are the most common cause of autosomal recessive juvenile-onset and young-onset parkinsonism. The few available detailed neuropathologic reports suggest that homozygous and compound heterozygous parkin mutations are characterized by severe substantia nigra pars compacta neuronal loss.

Objective

To investigate whether parkin -linked parkinsonism is a different clinicopathologic entity to Parkinson disease (PD).

Design, Setting, and Participants

We describe the clinical, genetic, and neuropathologic findings of 5 unrelated cases of parkin disease and compare them with 5 pathologically confirmed PD cases and 4 control subjects. The PD control cases and normal control subjects were matched first for age at death then disease duration (PD only) for comparison.

Results

Presenting signs in the parkin disease cases were hand or leg tremor often combined with dystonia. Mean age at onset was 34 years; all cases were compound heterozygous for mutations of parkin. Freezing of gait, postural deformity, and motor fluctuations were common late features. No patients had any evidence of cognitive impairment or dementia. Neuronal counts in the substantia nigra pars compacta revealed that neuronal loss in the parkin cases was as severe as that seen in PD, but relative preservation of the dorsal tier was seen in comparison with PD (P = .04). Mild neuronal loss was identified in the locus coeruleus and dorsal motor nucleus of the vagus, but not in the nucleus basalis of Meynert, raphe nucleus, or other brain regions. Sparse Lewy bodies were identified in 2 cases (brainstem and cortex).

Conclusions and Relevance

These findings support the notion that parkin disease is characterized by a more restricted morphologic abnormality than is found in PD, with predominantly ventral nigral degeneration and absent or rare Lewy bodies.

Postconcussion Syndrome After Mild Traumatic Brain Injury in Children and Adolescents Requires Further Detailed Study Postconcussion Syndrome and Traumatic Brain Injury

Butler IJ. — Wed, 01 May 2013 00:00:00 GMT

Objective:

To determine the acute predictors associated with the development of postconcussion syndrome (PCS) in children and adolescents after mild traumatic brain injury.

Design:

Retrospective analysis of a prospective observational study.

Setting:

Pediatric emergency department (ED) in a children's hospital.

Participants:

Four hundred six children and adolescents aged 5 to 18 years.

Main Exposure:

Closed head trauma.

Main Outcome Measures:

The Rivermead Post Concussion Symptoms Questionnaire administered 3 months after the injury.

Results:

Of the patients presenting to the ED with mild traumatic brain injury, 29.3% developed PCS. The most frequent PCS symptom was headache. Predictors of PCS, while controlling for other factors, were being of adolescent age, headache on presentation to the ED, and admission to the hospital. Patients who developed PCS missed a mean (SD) of 7.4 (13.9) days of school.

Conclusions:

Adolescents who have headache on ED presentation and require hospital admission at the ED encounter are at elevated risk for PCS after mild traumatic brain injury. Interventions to identify this population and begin early treatment may improve outcomes and reduce the burden of disease.

Prognosis of Mild Cognitive Impairment in Early Parkinson Disease The Norwegian ParkWest Study Cognitive Impairment in Early Parkinson Disease

Pedersen K, Larsen J, Tysnes O, et al. — Wed, 01 May 2013 00:00:00 GMT

Importance

Mild cognitive impairment (MCI) is common in Parkinson disease (PD), but the prognostic value of MCI in early PD is unknown.

Objective

To examine the course of MCI and its progression to dementia in an incident PD cohort.

Design

Prospective longitudinal cohort study.

Setting

The Norwegian ParkWest study, an ongoing population-based study of the incidence, neurobiology, and prognosis of PD in western and southern Norway.

Participants

A population-based cohort of 182 patients with incident PD monitored for 3 years.

Main Outcomes and Measures

Serial neuropsychological tests of attention, executive function, verbal memory, and visuospatial skills were administered at baseline, 1 year, and 3 years. Patients were classified as having MCI and received a diagnosis of dementia according to published consensus criteria.

Results

Significantly more patients with MCI than without MCI at baseline (10 of 37 [27.0%] vs 1 of 145 [0.7%]; relative risk, 39.2 [95% CI, 5.2-296.5]; P < .001) progressed to dementia during follow-up. Of those with MCI at baseline, 8 of 37 (21.6%) had MCI that reverted to normal cognition during follow-up. Mild cognitive impairment at the 1-year visit was associated with a similar progression rate to dementia (10 of 36 patients [27.8%]) and reversion rate to normal cognition (7 of 36 [19.4%]). However, among the 22 patients with persistent MCI at baseline and the 1-year visit, 10 (45.5%) developed dementia and only 2 (9.1%) had MCI that reverted to normal cognition by the end of study.

Conclusions and Relevance

Mild cognitive impairment at PD diagnosis predicts a highly increased risk for early dementia. Repeated neuropsychological testing increases the prognostic accuracy of MCI with respect to early dementia development in PD.

Proximal Dominant Hereditary Motor and Sensory Neuropathy With Proximal Dominance Association With Mutation in the TRK-Fused Gene Neuropathy Associated With TRK-Fused Gene Mutation

Lee S, Lee H, Park J, et al. — Wed, 01 May 2013 00:00:00 GMT

Importance

Hereditary motor and sensory neuropathy with proximal dominance (HMSN-P) has been reported as a rare type of autosomal dominant adult-onset Charcot-Marie-Tooth disease. HMSN-P has been described only in Japanese descendants since 1997, and the causative gene has not been found.

Objectives

To identify the genetic cause of HMSN-P in a Korean family and determine the pathogenic mechanism.

Design

Genetic and observational analysis.

Setting

Translational research center for rare neurologic disease.

Participants

Twenty-eight individuals (12 men and 16 women) from a Korean family with HMSN-P.

Main Outcome Measures

Whole-exome sequencing, linkage analysis, and magnetic resonance imaging.

Results

Through whole-exome sequencing, we revealed that HMSN-P is caused by a mutation in the TRK-fused gene (TFG). Clinical heterogeneities were revealed in HMSN-P between Korean and Japanese patients. The patients in the present report showed faster progression of the disease compared with the Japanese patients, and sensory nerve action potentials of the sural nerve were lost in the early stages of the disease. Moreover, tremor and hyperlipidemia were frequently found. Magnetic resonance imaging of the lower extremity revealed a distinct proximal dominant and sequential pattern of muscular involvement with a clearly different pattern than patients with Charcot-Marie-Tooth disease type 1A. Particularly, endoneural blood vessels revealed marked narrowing of the lumen with swollen vesicular endothelial cells.

Conclusions and Relevance

The underlying cause of HMSN-P proves to be a mutation in TFG that lies on chromosome 3q13.2. This disease is not limited to Japanese descendants, and marked narrowing of endoneural blood vessels was noted in the present study. We believe that TFG can affect the peripheral nerve tissue.

Pulsating Enophthalmos in Neurofibromatosis 1 Pulsating Enophthalmos in Neurofibromatosis 1

Lehn A, Airey C, Boyle R. — Wed, 01 May 2013 00:00:00 GMT

A 49-year-old man with neurofibromatosis 1 (NF1) presented to the neurology outpatient clinic with headaches and visual disturbance. He had typical clinical features of neurofibromatosis and was noted to have a pulsating enophthalmos. This had first been noted in childhood, when he was hospitalized for the removal of a spinal neurofibroma. Apart from severe, disabling headaches, he has not had any other major complications from NF1. His family history was notable for his mother, his siblings, and both his children all being affected by NF1, although with widely variable phenotypes.

Randomized Controlled Clinical Trial of “Virtual House Calls” for Parkinson Disease “Virtual House Calls” for Parkinson Disease

Dorsey E, Venkataraman V, Grana MJ, et al. — Wed, 01 May 2013 00:00:00 GMT

Importance

The burden of neurological disorders is increasing, but access to care is limited. Providing specialty care to patients via telemedicine could help alleviate this growing problem.

Objective

To evaluate the feasibility, effectiveness, and economic benefits of using web-based videoconferencing (telemedicine) to provide specialty care to patients with Parkinson disease in their homes.

Design

A 7-month, 2-center, randomized controlled clinical trial.

Setting

Patients' homes and outpatient clinics at 2 academic medical centers.

Participants

Twenty patients with Parkinson disease with Internet access at home.

Intervention

Care from a specialist delivered remotely at home or in person in the clinic.

Main Outcome Measures

The primary outcome variable was feasibility, as measured by the percentage of telemedicine visits completed as scheduled. Secondary outcome measures included clinical benefit, as measured by the 39-item Parkinson Disease Questionnaire, and economic value, as measured by time and travel.

Results

Twenty participants enrolled in the study and were randomly assigned to telemedicine (n = 9) or in-person care (n = 11). Of the 27 scheduled telemedicine visits, 25 (93%) were completed, and of the 33 scheduled in-person visits, 30 (91%) were completed (P = .99). In this small study, the change in quality of life did not differ for those randomly assigned to telemedicine compared with those randomly assigned to in-person care (4.0-point improvement vs 6.4-point improvement; P = .61). Compared with in-person visits, each telemedicine visit saved participants, on average, 100 miles of travel and 3 hours of time.

Conclusion and Relevance

Using web-based videoconferencing to provide specialty care at home is feasible, provides value to patients, and may offer similar clinical benefit to that of in-person care. Larger studies are needed to determine whether the clinical benefits are indeed comparable to those of in-person care and whether the results observed are generalizable.

Trial Registration

clinicaltrials.gov Identifier: NCT01476306

Risk Factors for β-Amyloid Deposition in Healthy Aging Vascular and Genetic Effects Factors for β-Amyloid Deposition in Healthy Aging

Rodrigue KM, Rieck JR, Kennedy KM, et al. — Wed, 01 May 2013 00:00:00 GMT

Importance

Identifying risk factors for increased β-amyloid (Aβ) deposition is important for targeting individuals most at risk for developing Alzheimer disease and informing clinical practice concerning prevention and early detection.

Objective

To investigate risk factors for Aβ deposition in cognitively healthy middle-aged and older adults. Specifically, we hypothesized that individuals with a vascular risk factor such as hypertension, in combination with a genetic risk factor for Alzheimer disease (apolipoprotein E ϵ4 allele), would show greater amyloid burden than those without such risk.

Design

Cross-sectional study.

Setting

General community.

Participants

One hundred eighteen well-screened and cognitively normal adults, aged 47 to 89 years. Participants were classified in the hypertension group if they reported a medical diagnosis of hypertension or if blood pressure exceeded 140 mm Hg systolic/90 mm Hg diastolic, as measured across 7 occasions at the time of study.

Intervention

Participants underwent Aβ positron emission tomography imaging with radiotracer fluorine 18–labeled florbetapir. Participants were genotyped for apolipoprotein E and were classified as ϵ4⁺ or ϵ4⁻.

Main Outcome Measure

Amyloid burden.

Results

Participants in the hypertension group with at least 1 ϵ4 allele showed significantly greater amyloid burden than those with only 1 risk factor or no risk factors. Furthermore, increased pulse pressure was strongly associated with increased mean cortical amyloid level for subjects with at least 1 ϵ4 allele.

Conclusions and Relevance

Vascular disease is a prevalent age-related condition that is highly responsive to both behavioral modification and medical treatment. Proper control and prevention of risk factors such as hypertension earlier in the life span may be one potential mechanism to ameliorate or delay neuropathological brain changes with aging.

Sleep Quality and Preclinical Alzheimer Disease Sleep Quality and Preclinical Alzheimer Disease

Ju YS, McLeland JS, Toedebusch CD, et al. — Wed, 01 May 2013 00:00:00 GMT

Importance

Sleep and circadian problems are very common in Alzheimer disease (AD). Recent animal studies suggest a bidirectional relationship between sleep and β-amyloid (Aβ), a key molecule involved in AD pathogenesis.

Objective

To test whether Aβ deposition in preclinical AD, prior to the appearance of cognitive impairment, is associated with changes in quality or quantity of sleep.

Design

Cross-sectional study conducted from October 2010 to June 2012.

Setting

General community volunteers at the Washington University Knight Alzheimer's Disease Research Center.

Participants

Cognitively normal individuals (n = 145) 45 years and older were recruited from longitudinal studies of memory and aging at the Washington University Knight Alzheimer's Disease Research Center. Valid actigraphy data were recorded in 142. The majority (124 of 142) were recruited from the Adult Children Study, in which all were aged 45 to 75 years at baseline and 50% have a parental history of late-onset AD. The rest were recruited from a community volunteer cohort in which all were older than 60 years and healthy at baseline.

Main Outcome Measures

Sleep was objectively measured using actigraphy for 2 weeks. Sleep efficiency, which is the percentage of time in bed spent asleep, was the primary measure of sleep quality. Total sleep time was the primary measure of sleep quantity. Cerebrospinal fluid Aβ42 levels were used to determine whether amyloid deposition was present or absent. Concurrent sleep diaries provided nap information.

Results

Amyloid deposition, as assessed by Aβ42 levels, was present in 32 participants (22.5%). This group had worse sleep quality, as measured by sleep efficiency (80.4% vs 83.7%), compared with those without amyloid deposition, after correction for age, sex, and APOE ϵ4 allele carrier status (P = .04). In contrast, quantity of sleep was not significantly different between groups, as measured by total sleep time. Frequent napping, 3 or more days per week, was associated with amyloid deposition (31.2% vs 14.7%; P = .03).

Conclusions and Relevance

Amyloid deposition in the preclinical stage of AD appears to be associated with worse sleep quality but not with changes in sleep quantity.

The Gender Gap in Multiple Sclerosis Intersection of Science and Society The Gender Gap in Multiple Sclerosis

Dunn SE, Steinman L. — Wed, 01 May 2013 00:00:00 GMT

More than 3 times more women than men have multiple sclerosis (MS). Over the past 50 years, this ratio has been steadily increasing. The burdens to those who battle this disease, as well as the costs for society in dealing with MS, are substantial, and deciphering this 50-year-old trend in female preponderance in this disease is critical. In attempting to understand this growing imbalance, a number of intriguing discoveries have been made. These discoveries illuminate the pathogenesis of MS, with applications and benefits for both men and women. These breakthroughs potentially allow for the repurposing of certain approved drugs for potential use as treatments of MS.

Tissue Plasminogen Activator and Calcific Emboli Tissue Plasminogen Activator and Calcific Emboli

Gokhale S, Lahoti S, Rojas R, et al. — Wed, 01 May 2013 00:00:00 GMT

A 93-year-old right-handed woman was seen within an hour of acutely developing aphasia and right hemiplegia. She had a history of hypertension and hypercholesterolemia and had smoked 30 pack-years; medications included aspirin, hydrochlorothiazide, and amlodipine besylate. She had no history of arrhythmia.