Neurology May 2012 Volume 78 Issue 20

Objective: To delineate the temporal patterns of outcome and to determine the probability of seizure freedom with successive antiepileptic drug regimens in newly diagnosed epilepsy.Methods: Patients in whom epilepsy was diagnosed and the first antiepileptic drug prescribed between July 1, 1982, and April 1, 2006, were followed up until March 31, 2008. Outcomes were categorized into 4 patterns: A) early and sustained seizure freedom; B) delayed but sustained seizure freedom; C) fluctuation between periods of seizure freedom and relapse; and D) seizure freedom never attained. Probability of seizure freedom with successive drug regimens was compared. Seizure freedom was defined as no seizures for >=1 year.Results: A total of 1,098 patients were included (median age 32 years, range 9-93). At the last clinic visit, 749 (68%) patients were seizure-free, 678 (62%) on monotherapy. Outcome pattern A was observed in 408 (37%), pattern B in 246 (22%), pattern C in 172 (16%), and pattern D in 272 (25%) patients. There was a higher probability of seizure freedom in patients receiving 1 compared to 2 drug regimens, and 2 compared to 3 regimens (p < 0.001). The difference was greater among patients with symptomatic or cryptogenic than with idiopathic epilepsy. Less than 2% of patients became seizure-free on subsequent regimens but a few did so on their sixth or seventh regimen.Conclusions: Most patients with newly diagnosed epilepsy had a constant course which could usually be predicted early. The chance of seizure freedom declined with successive drug regimens, most markedly from the first to the third and among patients with localization-related epilepsies.GLOSSARY: AED: antiepileptic drugILAE: International League Against EpilepsyIQR: interquartile rangeNGPSE: National General Practice Study of Epilepsy.(C)2012 American Academy of Neurology

Objectives: Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive lysosomal lipid storage disorder that is invariably fatal. NP-C diagnosis can be delayed for years due to heterogeneous presentation; adult-onset NP-C can be particularly difficult to diagnose. We developed a Suspicion Index tool, ranking specific symptoms within and across domains, including family members who have NP-C, to provide a risk prediction score to identify patients who should undergo testing for NP-C.Methods: A retrospective chart review was performed in 5 centers in Europe and 2 in Australia (n = 216). Three patient types were selected: classic or variant filipin staining NP-C cases (n = 71), NP-C noncases (confirmed negative by filipin staining; n = 64), or controls with at least 1 characteristic symptom of NP-C (n = 81). NP-C signs and symptoms were categorized into visceral, neurologic, or psychiatric domains. Logistic regression was performed on individual signs and symptoms within and across domains, and regression coefficients were used to develop prediction scores for NP-C. Internal validation was performed with the bootstrap resampling method.Results: The Suspicion Index tool has good discriminatory performance with cutpoints for grading suspicion of NP-C. Neonatal jaundice/cholestasis, splenomegaly, vertical supranuclear gaze palsy, cataplexy, and cognitive decline/dementia were strong predictors of NP-C, as well as symptoms occurring in multiple domains in individual patients, and also parents/siblings or cousins with NP-C.Conclusions: The Suspicion Index tool is a screening tool that can help identify patients who may warrant further investigation for NP-C. A score >=70 indicates that patients should be referred for testing for NP-C.GLOSSARY: CI: confidence intervalNP-C: Niemann-Pick disease type CROC: receiver operating characteristic.(C)2012 American Academy of Neurology

Objective: Recommendations for the diagnosis of preclinical Alzheimer disease (AD) have been formulated by a workgroup of the National Institute on Aging and Alzheimer's Association. Three stages of preclinical AD were described. Stage 1 is characterized by abnormal levels of [beta]-amyloid. Stage 2 represents abnormal levels of [beta]-amyloid and evidence of brain neurodegeneration. Stage 3 includes the features of stage 2 plus subtle cognitive changes. Stage 0, not explicitly defined in the criteria, represents subjects with normal biomarkers and normal cognition. The ability of the recommended criteria to predict progression to cognitive impairment is the crux of their validity.Methods: Using previously developed operational definitions of the 3 stages of preclinical AD, we examined the outcomes of subjects from the Mayo Clinic Study of Aging diagnosed as cognitively normal who underwent brain MRI or [18F]fluorodeoxyglucose and Pittsburgh compound B PET, had global cognitive test scores, and were followed for at least 1 year.Results: Of the 296 initially normal subjects, 31 (10%) progressed to a diagnosis of mild cognitive impairment (MCI) or dementia (27 amnestic MCI, 2 nonamnestic MCI, and 2 non-AD dementias) within 1 year. The proportion of subjects who progressed to MCI or dementia increased with advancing stage (stage 0, 5%; stage 1, 11%; stage 2, 21%; stage 3, 43%; test for trend, p < 0.001).Conclusions: Despite the short follow-up period, our operationalization of the new preclinical AD recommendations confirmed that advancing preclinical stage led to higher proportions of subjects who progressed to MCI or dementia.GLOSSARY: AA: Alzheimer's AssociationAD: Alzheimer diseaseAVLT: Auditory Verbal Learning TestBNT: Boston Naming TestCN: cognitively normalDSM-IV: Diagnostic and Statistical Manual of Mental Disorders, 4th editionFDG: fluorodeoxyglucoseHVa: hippocampal volume adjusted for total intracranial volumeIQR: interquartile rangeMCI: mild cognitive impairmentMCSA: Mayo Clinic Study of AgingNIA-AA: National Institute on Aging and Alzheimer's AssociationPiB: Pittsburgh compound BROI: region of interestSNAP: suspected non-Alzheimer pathwayTMT: Trail Making TestWAIS-R: Wechsler Adult Intelligence Scale-RevisedWMS-R: Wechsler Memory Scale-Revised.(C)2012 American Academy of Neurology

Objective: Utilization of postacute care is associated with improved poststroke outcomes. However, more than 20% of American adults under age 65 are uninsured. We sought to determine whether insurance status is associated with utilization and intensity of institutional postacute care among working age stroke survivors.Methods: A retrospective cross-sectional study of ischemic stroke survivors under age 65 from the 2004-2006 Nationwide Inpatient Sample was conducted. Hierarchical logistic regression models controlling for patient and hospital-level factors were used. The primary outcome was utilization of any institutional postacute care (inpatient rehabilitation or skilled nursing facilities) following hospital admission for ischemic stroke. Intensity of rehabilitation was explored by comparing utilization of inpatient rehabilitation facilities and skilled nursing facilities.Results: Of the 33,917 working age stroke survivors, 19.3% were uninsured, 19.8% were Medicaid enrollees, and 22.8% were discharged to institutional postacute care. Compared to those privately insured, uninsured stroke survivors were less likely (adjusted odds ratio [AOR] 0.53, 95% confidence interval [CI] 0.47-0.59) while stroke survivors with Medicaid were more likely to utilize any institutional postacute care (AOR = 1.40, 95% CI 1.27-1.54). Among stroke survivors who utilized institutional postacute care, uninsured (AOR = 0.48, 95% CI 0.36-0.64) and Medicaid stroke survivors (AOR = 0.27, 95% CI 0.23-0.33) were less likely to utilize an inpatient rehabilitation facility than a skilled nursing facility compared to privately insured stroke survivors.Conclusions: Insurance status among working age acute stroke survivors is independently associated with utilization and intensity of institutional postacute care. This may explain differences in poststroke outcomes among uninsured and Medicaid stroke survivors compared to the privately insured.GLOSSARY: AHRQ: Agency for Healthcare Research and QualityAOR: adjusted odds ratioCI: confidence intervalED: Emergency DepartmentHCUP: Healthcare Cost and Utilization ProjectICD: International Classification of DiseasesIRF: inpatient rehabilitation facilityNIS: Nationwide Inpatient SampleOR: odds ratioPAC: postacute careSNF: skilled nursing facility(C)2012 American Academy of Neurology

Objective: To describe 16 patients with a coincidence of 2 rare diseases: aquaporin-4 antibody (AQP4-Ab)-mediated neuromyelitis optica spectrum disorder (AQP4-NMOSD) and acetylcholine receptor antibody (AChR-Ab)-mediated myasthenia gravis (AChR-MG).Methods: The clinical details and antibody results of 16 patients with AChR-MG and AQP4-NMOSD were analyzed retrospectively.Results: All had early-onset AChR-MG, the majority with mild generalized disease, and a high proportion achieved remission. Fifteen were female; 11 were Caucasian. In 14/16, the MG preceded NMOSD (median interval: 16 years) and 11 of these had had a thymectomy although 1 only after NMOSD onset. In 4/5 patients tested, AQP4-Abs were detectable between 4 and 16 years prior to disease onset, including 2 patients with detectable AQP4-Abs prior to thymectomy. AChR-Abs decreased and the AQP4-Ab levels increased over time in concordance with the relevant disease. AChR-Abs were detectable at NMOSD onset in the one sample available from 1 of the 2 patients with NMOSD before MG.Conclusions: Although both conditions are rare, the association of MG and NMOSD occurs much more frequently than by chance and the MG appears to follow a benign course. AChR-Abs or AQP4-Abs may be present years before onset of the relevant disease and the antibody titers against AQP4 and AChR tend to change in opposite directions. Although most cases had MG prior to NMOSD onset, and had undergone thymectomy, NMOSD can occur first and in patients who have not had their thymus removed.GLOSSARY: Ab: antibodiesAChR-Ab: acetylcholine receptor antibodyAChR-MG: acetylcholine receptor antibody-mediated myasthenia gravisAQP4-Ab: aquaporin-4 antibodyAQP4-NMOSD: aquaporin-4 antibody-mediated neuromyelitis optica spectrum disorderIgG: immunoglobulin GIS: immunosuppressiveLETM: longitudinally extensive transverse myelitisMG: myasthenia gravisNMO: neuromyelitis opticaNMOSD: neuromyelitis optica spectrum disorderOCB: oligoclonal bandsON: optic neuritisSLE: systemic lupus erythematosusVGKC: voltage-gated potassium channel(C)2012 American Academy of Neurology

GLOSSARY: ADOA: autosomal dominant optic atrophyATP: adenosine triphosphateCMT: Charcot-Marie-Tooth diseaseDLP1: dynamin-like protein 1DLP1: dynamin-like protein 1 geneDRP1: dynamin-related protein 1DRP1: dynamin-related protein 1 geneEGR2: early growth response 2 geneEOP: early-onset Parkinson diseaseGDAP1: ganglioside-induced differentiation-associated protein 1GDAP1: ganglioside-induced differentiation-associated protein 1 geneGST: glutathione-S-transferaseHAP1: huntingtin-associated proteinLHON: Leber hereditary optic neuropathyMFF: mitochondrial fission factorMFN: mitofusinMFN2: mitofusin 2 geneMIEF: mitochondrial elongation factormtDNA: mitochondrial DNAOPA1: optic atrophy type 1 genePARK2: parkin genePARL: presenilin-associated rhomboid-like proteinPINK1: PTEN-induced putative kinase protein-1PINK1: PTEN-induced kinase 1 genePD: Parkinson disease(C)2012 American Academy of Neurology