Neurology January 2013 Volume 80 Issue 4

Objectives: To determine the prognostic value of an EEG grading scale and clinical outcome of treated seizures detected with continuous EEG (cEEG) during therapeutic hypothermia (TH) and rewarming post cardiac arrest (CA).Methods: Our cohort study retrospectively reviewed the electronic medical records and cEEGs of all patients undergoing TH after CA under protocol over 2 years. cEEG was initiated during TH and continued until restoration of normothermia (NT). EEGs were graded 1-3 (3 = most severe) using a departmentally developed EEG severity grading scale by 2 authors blinded to clinical outcome. Outcome was measured using the Cerebral Performance Category scale; grades 1-2 were considered a "good" outcome, 3-5 "poor."Results: Fifty-four patients were included; 51 remained on cEEG through NT. Nineteen died. EEG severity grading during both TH and NT statistically correlated with outcome (grade 1 = good, grade 3 = poor). Other EEG features correlating with poor outcome included seizures, nonreactive background, and epileptiform discharges. Changes in EEG grade during monitoring did not statistically correlate with outcome. Five patients had seizures; all occurred in patients with grade 3 EEG backgrounds and all had a poor outcome.Conclusion: Grades 1 and 3 on our EEG severity grading scale during TH and NT correlated with outcome. Treating seizures did not improve outcome in our cohort.(C)2013 American Academy of Neurology

Objective: Recent publications show that using imagery instructions, brain activation patterns indicating consciousness can be found in approximately 10% of patients with unresponsive wakefulness syndrome (UWS; previously called vegetative state). It is possible, however, that patients who cannot follow instructions (because of limited memory/attention capacities, for example) are nevertheless conscious and retain emotional abilities to feel pain and pleasure. The aim of this study was to assess residual affective consciousness in a specific network of brain structures, the so-called pain matrix (PM) of the brain.Methods: We examined 44 carefully diagnosed UWS patients at 2 imaging centers. fMRI was used to investigate the brain hemodynamic responses to (a) imagery instructions, and (b) pain cries as opposed to neutral human vocalizations.Results: In line with the data of other groups, consistent responses to imagery instructions were obtained in 5 patients. In contrast, the PM was activated by pain cries in 24 patients. The PM consists of a sensory subsystem, which underlies pain sensation, and an affective subsystem, which underlies the characteristic aversive emotional tone of pain. The former was activated in 34% of patients, the latter in 30% of patients.Conclusion: Although there is debate about whether patients with UWS can perceive their own pain, our data indicate that many of them respond to the signals of pain in others. One can speculate that "affective consciousness" can remain even in patients with very severe brain damage who have no capacity for cognition.(C)2013 American Academy of Neurology

Objective: To examine the relationships between apolipoprotein E (APOE) [Latin Small Letter Open E]4 dose and in vivo distributions of both fibrillary amyloid burden and glucose metabolism in the same Alzheimer disease dementia patients, selected for abnormal amyloid imaging.Methods: Twenty-two APOE [Latin Small Letter Open E]4 negative, 40 heterozygous, and 22 homozygous Alzheimer disease dementia patients underwent dynamic (90 minutes) [11C]Pittsburgh compound B (PIB) and static [18F]fluorodeoxyglucose (FDG) PET scans. Parametric nondisplaceable binding potential images of [11C]PIB and standardized uptake value ratio images of [18F]FDG were generated using cerebellar gray matter as reference tissue. Frontal, parietal, temporal, posterior cingulate, and occipital cortices were selected as regions of interest.Results: Multivariate general linear models with adjustment for age, sex, and Mini-Mental State Examination showed main effects of APOE [Latin Small Letter Open E]4 dose on distributions of both [11C]PIB (p for trend <0.05) and [18F]FDG (p for trend <0.01). More specifically, a univariate general linear model of individual regions showed increased [11C]PIB binding in frontal cortex of APOE [Latin Small Letter Open E]4 noncarriers compared with APOE [Latin Small Letter Open E]4 carriers (p < 0.05). In contrast, APOE [Latin Small Letter Open E]4 carriers had reduced [18F]FDG uptake in occipital cortex (p < 0.05) and a borderline significant effect in posterior cingulate (p = 0.07) in a dose-dependent manner.Conclusion: We found a reversed APOE [Latin Small Letter Open E]4 dose effect for amyloid deposition in the frontal lobe, whereas APOE [Latin Small Letter Open E]4 carriership was associated with more profound metabolic impairment in posterior parts of the cortex. These findings suggest that APOE genotype has a differential effect on the distribution of amyloid plaques and glucose metabolism. This may have important implications for emerging therapies that aim to directly intervene in the disease process.(C)2013 American Academy of Neurology

Objective: To describe the prevalence of neurocognitive impairment (NCI) among early diagnosed and managed HIV-infected persons (HIV+) compared to HIV-negative controls.Methods: We performed a cross-sectional study among 200 HIV+ and 50 matched HIV-uninfected (HIV-) military beneficiaries. HIV+ patients were categorized as earlier (<6 years of HIV, no AIDS-defining conditions, and CD4 nadir >200 cells/mm3) or later stage patients (n = 100 in each group); both groups were diagnosed early and had access to care. NCI was diagnosed using a comprehensive battery of standardized neuropsychological tests.Results: HIV+ patients had a median age of 36 years, 91% were seroconverters (median window of 1.2 years), had a median duration of HIV of 5 years, had a CD4 nadir of 319, had current CD4 of 546 cells/mm3, and 64% were on highly active antiretroviral therapy (initiated 1.3 years after diagnosis at a median CD4 of 333 cells/mm3). NCI was diagnosed among 38 (19%, 95% confidence interval 14%-25%) HIV+ patients, with a similar prevalence of NCI among earlier and later stage patients (18% vs 20%, p = 0.72). The prevalence of NCI among HIV+ patients was similar to HIV- patients.Conclusions: HIV+ patients diagnosed and managed early during the course of HIV infection had a low prevalence of NCI, comparable to matched HIV-uninfected persons. Early recognition and management of HIV infection may be important in limiting neurocognitive impairment.(C)2013 American Academy of Neurology

Objective: To identify brain regions with metabolic changes in DYT11 myoclonus-dystonia (DYT11-MD) relative to control subjects and to compare metabolic abnormalities in DYT11-MD with those found in other forms of hereditary dystonia and in posthypoxic myoclonus.Methods: [18F]-fluorodeoxyglucose PET was performed in 6 subjects with DYT11-MD (age 30.5 +/- 10.1 years) and in 6 nonmanifesting DYT11 mutation carriers (NM-DYT11; age 59.1 +/- 8.9 years) representing the parental generation of the affected individuals. These data were compared to scan data from age-matched healthy control subjects using voxel-based whole brain searches and group differences were considered significant at p < 0.05 (corrected, statistical parametric mapping). As a secondary analysis, overlapping abnormalities were identified by comparisons to hereditary dystonias (DYT1, DYT6, dopa-responsive dystonia) and to posthypoxic myoclonus.Results: We found significant DYT11 genotype-specific metabolic increases in the inferior pons and in the posterior thalamus as well as reductions in the ventromedial prefrontal cortex. Significant phenotype-related increases were present in the parasagittal cerebellum. This latter abnormality was shared with posthypoxic myoclonus, but not with other forms of dystonia. By contrast, all dystonia cohorts exhibited significant metabolic increases in the superior parietal lobule.Conclusions: The findings are consistent with a subcortical myoclonus generator in DYT11-MD, likely involving the cerebellum. By contrast, subtle increases in the superior parietal cortex relate to the additional presence of dystonic symptoms. Although reduced penetrance in DYT11-MD has been attributed to the maternal imprinting epsilon-sarcoglycan mutations, NM-DYT11 carriers showed significant metabolic abnormalities that are not explained by this genetic model.(C)2013 American Academy of Neurology

Objectives: Levetiracetam is a broad-spectrum antiepileptic drug (AED) which is currently licensed in the United States and the United Kingdom and Ireland for use as adjunctive treatment of focal-onset seizures and myoclonic seizures or generalized tonic-clonic seizures, occurring as part of generalized epilepsy syndromes. In the United Kingdom and Ireland, it is also licensed as monotherapy treatment for focal-onset seizures. Previous small studies have suggested a low risk for major congenital malformations (MCM) with levetiracetam use in pregnancy.Methods: The UK and Ireland Epilepsy and Pregnancy Registers are prospective, observational registration and follow-up studies that were set up to determine the relative safety of all AEDs taken in pregnancy. Here we report our combined results for first-trimester exposures to levetiracetam from October 2000 to August 2011.Results: Outcome data were available for 671 pregnancies. Of these, 304 had been exposed to levetiracetam in monotherapy, and 367 had been exposed to levetiracetam in combination with at least one other AED. There were 2 MCM in the monotherapy group (0.70%; 95% confidence interval [CI] 0.19%-2.51%) and 19 in the polytherapy group (6.47%; 4.31%-9.60%). The MCM rate in the polytherapy group varied by AED regimen, with lower rates when levetiracetam was given with lamotrigine (1.77%; 95% CI 0.49%-6.22%) than when given with valproate (6.90%; 95% CI 1.91%-21.96%) or carbamazepine (9.38%; 95% CI 4.37%-18.98%).Conclusion: This study, in a meaningful number of exposed pregnancies, confirms a low risk for MCM with levetiracetam monotherapy use in pregnancy. MCM risk is higher when levetiracetam is taken as part of a polytherapy regimen, although further work is required to determine the risks of particular combinations. With respect to MCM, levetiracetam taken in monotherapy can be considered a safer alternative to valproate for women with epilepsy of childbearing age.(C)2013 American Academy of Neurology

Fatigue is commonly reported in many neurologic illnesses, including multiple sclerosis, Parkinson disease, myasthenia gravis, traumatic brain injury, and stroke. Fatigue contributes substantially to decrements in quality of life and disability in these illnesses. Despite the clear impact of fatigue as a disabling symptom, our understanding of fatigue pathophysiology is limited and current treatment options rarely lead to meaningful improvements in fatigue. Progress continues to be hampered by issues related to terminology and assessment. In this article, we propose a unified taxonomy and a novel assessment approach to addressing distinct aspects of fatigue and fatigability in clinical and research settings. This taxonomy is based on our current knowledge of the pathophysiology and phenomenology of fatigue and fatigability. Application of our approach indicates that the assessment and reporting of fatigue can be clarified and improved by utilizing this taxonomy and creating measures to address distinct aspects of fatigue and fatigability. We review the strengths and weaknesses of several common measures of fatigue and suggest, based on our model, that many research questions may be better addressed by using multiple measures. We also provide examples of how to apply and validate the taxonomy and suggest directions for future research.(C)2013 American Academy of Neurology