Neurology October 2012 Volume 79 Issue 17

Objectives: Gray matter (GM) atrophy is common in multiple sclerosis (MS), as is cognitive dysfunction. Understanding the exact relationship between atrophy and cognition requires further investigation. The aim of this study was to investigate the relationship between subcortical GM atrophy and cognition in early relapsing onset MS.Methods: Structural MRI and neuropsychological evaluations were performed in 120 patients (80 women) and 50 controls (30 women), part of an early inception cohort, 6 years postdiagnosis. Deep GM volumes were segmented automatically. Cognition was assessed in 7 domains. Stepwise linear regression was used to predict average cognition in the patient group.Results: Most deep GM volumes were reduced in patients, with larger effects on average in men (-11%) than in women (-6.3%). Only the bilateral hippocampus, amygdala, and right nucleus accumbens in men, and right hippocampus and nucleus accumbens, bilateral amygdala, and putamen in women, showed no atrophy compared to controls. All cognitive domains except visuospatial memory were affected in men; none were significantly affected in women. In the MS group, average cognition was best predicted by thalamic volume, sex, and education (adjusted R2 = 0.31), while lesion volume was not a significant predictor in the model.Conclusions: Six years postdiagnosis, almost all subcortical structures were affected by MS, especially in men. Cognition was most severely affected in male patients. Thalamic volume, sex, and education best predicted average cognition. These results underline the relevance of specific subcortical structures to cognition, as well as the relevance of (sex-specific) atrophy in MS.GLOSSARY: BRB-N: Brief Repeatable Battery for Neurological diseaseDGM: deep gray matterDMT: disease-modifying therapyEDSS: Expanded Disability Status ScaleGLM: general linear modelGM: gray matterMS: multiple sclerosisNBV: normalized whole brain volumeNCGMV: normalized cortical gray matter volumeNDGMV: normalized deep gray matter volumeNGMV: normalized total gray matter volumeNWMV: normalized total white matter volumeRRMS: relapsing-remitting multiple sclerosisWM: white matter(C)2012 American Academy of Neurology

Objective: Parkinson disease (PD), a devastating neurodegenerative disorder, affects motor abilities and cognition as well. It is not clear whether the proapoptotic protein, Bid, is involved in tumor necrosis factor death receptor I (TNFRI)-mediated destructive signal transduction pathways such as cell dysfunction or neurodegeneration in the temporal cortex of patients with PD.Methods: Molecular and biochemical approaches were used to dissect mitochondrial related components of the destructive signaling pathway in the temporal cortex from rapidly autopsied brains (postmortem interval mean 2.6 hours). Brains from patients with PD (n = 15) had an average age of 81.4 years, compared to the average age of 84.36 years in age-matched control patient brains (n = 15).Results: TNFRI and its adaptor protein, TRADD, were not only present in the cytoplasm of the temporal cortex, but were significantly elevated (42.3% and 136.1%, respectively) in PD brains compared to age-matched control brains. Bid in the PD temporal cortex could be further cleaved into tBid in the cytosol, which is translocated into the mitochondria, where cytochrome c is then released and caspase-3 is subsequently activated.Conclusion: Patients with PD have an activated Bid-mediated destructive signal pathway via TNFRI in the temporal cortex. Such deficits are pervasive, suggesting that they might contribute to cortex degeneration as PD manifests.GLOSSARY: AD: Alzheimer diseaseBBDP: brain and body donation programDD: death domainFADD: Fas-associated death domainGFAP: glial fibrillary acid proteinNPC: nonpathologic controlPD: Parkinson diseaseSDS-PAGE: sodium dodecyl sulfate polyacrylamide gel electrophoresisSN: substantia nigraTNF: tumor necrosis factorTNFRI: tumor necrosis factor death receptor ITRADD: tumor necrosis factor death receptor I-associated death domain protein(C)2012 American Academy of Neurology

Objectives: We describe temporal trends in stroke incidence stratified by age from our population-based stroke epidemiology study. We hypothesized that stroke incidence in younger adults (age 20-54) increased over time, most notably between 1999 and 2005.Methods: The Greater Cincinnati/Northern Kentucky region includes an estimated population of 1.3 million. Strokes were ascertained in the population between July 1, 1993, and June 30, 1994, and in calendar years 1999 and 2005. Age-, race-, and gender-specific incidence rates with 95 confidence intervals were calculated assuming a Poisson distribution. We tested for differences in age trends over time using a mixed-model approach, with appropriate link functions.Results: The mean age at stroke significantly decreased from 71.2 years in 1993/1994 to 69.2 years in 2005 (p < 0.0001). The proportion of all strokes under age 55 increased from 12.9% in 1993/1994 to 18.6% in 2005. Regression modeling showed a significant change over time (p = 0.002), characterized as a shift to younger strokes in 2005 compared with earlier study periods. Stroke incidence rates in those 20-54 years of age were significantly increased in both black and white patients in 2005 compared to earlier periods.Conclusions: We found trends toward increasing stroke incidence at younger ages. This is of great public health significance because strokes in younger patients carry the potential for greater lifetime burden of disability and because some potential contributors identified for this trend are modifiable.GLOSSARY: CHD: coronary heart diseaseGCNKSS: Greater Cincinnati/Northern Kentucky Stroke StudyICD: International Classification of DiseasesICH: intracerebral hemorrhageNHANES: National Health and Nutrition Examination SurveySAH: subarachnoid hemorrhage(C)2012 American Academy of Neurology

Objective: To determine whether the absence of early epileptiform abnormalities predicts absence of later seizures on continuous EEG monitoring of hospitalized patients.Methods: We retrospectively reviewed 242 consecutive patients without a prior generalized convulsive seizure or active epilepsy who underwent continuous EEG monitoring lasting at least 18 hours for detection of nonconvulsive seizures or evaluation of unexplained altered mental status. The findings on the initial 30-minute screening EEG, subsequent continuous EEG recordings, and baseline clinical data were analyzed. We identified early EEG findings associated with absence of seizures on subsequent continuous EEG.Results: Seizures were detected in 70 (29%) patients. A total of 52 patients had their first seizure in the initial 30 minutes of continuous EEG monitoring. Of the remaining 190 patients, 63 had epileptiform discharges on their initial EEG, 24 had triphasic waves, while 103 had no epileptiform abnormalities. Seizures were later detected in 22% (n = 14) of studies with epileptiform discharges on their initial EEG, vs 3% (n = 3) of the studies without epileptiform abnormalities on initial EEG (p < 0.001). In the 3 patients without epileptiform abnormalities on initial EEG but with subsequent seizures, the first epileptiform discharge or electrographic seizure occurred within the first 4 hours of recording.Conclusions: In patients without epileptiform abnormalities during the first 4 hours of recording, no seizures were subsequently detected. Therefore, EEG features early in the recording may indicate a low risk for seizures, and help determine whether extended monitoring is necessary.GLOSSARY: cEEG: continuous EEGHIE: hypoxic-ischemic encephalopathyNCS: nonconvulsive seizurePED: periodic epileptiform dischargeSAH: subarachnoid hemorrhageTBI: traumatic brain injury(C)2012 American Academy of Neurology

Objectives: Alzheimer disease (AD) can now be diagnosed in subjects with mild cognitive impairment (MCI) using biomarkers. However, little is known about the rate of decline in those subjects. In this cohort study, we aimed to assess the conversion rate to dementia and identify prognostic markers in subjects with MCI and evidence of amyloid pathology.Methods: We pooled subjects from the VU University Medical Center Alzheimer Center and the Development of Screening Guidelines and Criteria for Predementia Alzheimer's Disease (DESCRIPA) study. We included subjects with MCI, an abnormal level of [beta]-amyloid1-42 (A[beta]1-42) in the CSF, and at least one diagnostic follow-up visit. We assessed the effect of APOE genotype, CSF total tau (t-tau) and tau phosphorylated at threonine 181 (p-tau) and hippocampal volume on time to AD-type dementia using Cox proportional hazards models and on decline on the Mini-Mental State Examination (MMSE) using linear mixed models.Results: We included 110 subjects with MCI with abnormal CSF A[beta]1-42 and a mean MMSE score of 26.3 +/- 2.8. During a mean follow-up of 2.2 +/- 1.0 (range 0.4-5.0) years, 63 subjects (57%) progressed to AD-type dementia. Abnormal CSF t-tau (hazard ratio [HR] 2.3, 95% confidence interval [CI] 1.1-4.6, p = 0.03) and CSF p-tau (HR 3.5, 95% CI 1.3-9.2, p = 0.01) concentration and hippocampal atrophy (HR 2.5, 95% CI 1.1-5.6, p = 0.02) predicted time to dementia. For subjects with both abnormal t-tau concentration and hippocampal atrophy, HR was 7.3 (95% CI 1.0-55.9, p = 0.06). Furthermore, abnormal CSF t-tau and p-tau concentrations and hippocampal atrophy predicted decline in MMSE score.Conclusions: In subjects with MCI and evidence of amyloid pathology, the injury markers CSF t-tau and p-tau and hippocampal atrophy can predict further cognitive decline.GLOSSARY: A[beta]1-42: [beta]-amyloid1-42AD: Alzheimer diseaseCI: confidence intervalDESCRIPA: Development of Screening Guidelines and Criteria for Predementia Alzheimer's DiseaseDSM-IV: Diagnostic and Statistical Manual of Mental Disorders, 4th editionHR: hazard ratioMCI: mild cognitive impairmentMMSE: Mini-Mental State Examinationp-tau: tau phosphorylated at threonine 181t-tau: total tauTMT: Trail Making TestVUmc: VU University Medical Center(C)2012 American Academy of Neurology

Objective: To assess the strengths and weaknesses of neurology resident education using survey methodology.Methods: A 27-question survey was sent to all neurology residents completing residency training in the United States in 2011.Results: Of eligible respondents, 49.8% of residents returned the survey. Most residents believed previously instituted duty hour restrictions had a positive impact on resident quality of life without impacting patient care. Most residents rated their faculty and clinical didactics favorably. However, many residents reported suboptimal preparation in basic neuroscience and practice management issues. Most residents (71%) noted that the Residency In-service Training Examination (RITE) assisted in self-study. A minority of residents (14%) reported that the RITE scores were used for reasons other than self-study. The vast majority (86%) of residents will enter fellowship training following residency and were satisfied with the fellowship offers they received.Conclusions: Graduating residents had largely favorable neurology training experiences. Several common deficiencies include education in basic neuroscience and clinical practice management. Importantly, prior changes to duty hours did not negatively affect the resident perception of neurology residency training.GLOSSARY: AAN: American Academy of NeurologyACGME: Accreditation Council for Graduate Medical EducationCNRF: Consortium of Neurology Residents and FellowsGES: Graduate Education SubcommitteeMRS: member research subcommitteeNCS: nerve conduction studiesRITE: Residency In-service Training Examination(C)2012 American Academy of Neurology