Neurology June 2012 Volume 78 Issue 24

Objective: To develop and validate a simple, integer-based score to predict functional outcome in acute ischemic stroke (AIS) using variables readily available after emergency room admission.Methods: Logistic regression was performed in the derivation cohort of previously independent patients with AIS (Acute Stroke Registry and Analysis of Lausanne [ASTRAL]) to identify predictors of unfavorable outcome (3-month modified Rankin Scale score >2). An integer-based point-scoring system for each covariate of the fitted multivariate model was generated by their [beta]-coefficients; the overall score was calculated as the sum of the weighted scores. The model was validated internally using a 2-fold cross-validation technique and externally in 2 independent cohorts (Athens and Vienna Stroke Registries).Results: Age (A), severity of stroke (S) measured by admission NIH Stroke Scale score, stroke onset to admission time (T), range of visual fields (R), acute glucose (A), and level of consciousness (L) were identified as independent predictors of unfavorable outcome in 1,645 patients in ASTRAL. Their [beta]-coefficients were multiplied by 4 and rounded to the closest integer to generate the score. The area under the receiver operating characteristic curve (AUC) of the score in the ASTRAL cohort was 0.850. The score was well calibrated in the derivation (p = 0.43) and validation cohorts (0.22 [Athens, n = 1,659] and 0.49 [Vienna, n = 653]). AUCs were 0.937 (Athens), 0.771 (Vienna), and 0.902 (when pooled). An ASTRAL score of 31 indicates a 50% likelihood of unfavorable outcome.Conclusions: The ASTRAL score is a simple integer-based score to predict functional outcome using 6 readily available items at hospital admission. It performed well in double external validation and may be a useful tool for clinical practice and stroke research.GLOSSARY: AIS: acute ischemic strokeASTRAL: Acute Stroke Registry and Analysis of LausanneASTRAL score: age, severity, time delay between stroke onset (or last proof of good health) and admission, range of visual field defect, acute glucose, and level of consciousnessAUC: area under the receiver operating characteristic curveBI: Barthel IndexBOAS: Bologna Outcome Algorithm for StrokemRS: modified Rankin ScaleNIHSS: NIH Stroke ScaleSSV: Six Simple VariablesVIF: variance inflation factor(C)2012 American Academy of Neurology

Objectives: The oscillation model of Parkinson disease (PD) states that, in the subthalamic nucleus (STN), increased [theta] (4-10 Hz) and [beta] (11-30 Hz) frequencies were associated with worsening whereas [gamma] frequencies (31-100 Hz) were associated with improvement of motor symptoms. However, the peak STN frequency in each band varied widely from subject to subject. We hypothesized that STN deep brain stimulation (DBS) at individualized [gamma] frequencies would improve whereas [theta] or [beta] frequencies would worsen PD motor signs.Methods: We prospectively studied 13 patients with PD. STN local field potential (LFP) was recorded after electrode implantations, in the OFF and then in ON dopaminergic medication states while patients performed wrist movements. Six individual peak frequencies of the STN LFP power spectra were obtained: the greatest decrease in [theta] and [beta] and greatest increase in [gamma] frequencies in the ON state (MED) and during movements (MOVE). Eight DBS frequencies were applied including 6 MED and MOVE frequencies, high frequency (HF) used for chronic stimulation, and no stimulation. The patients were assessed using the motor Unified Parkinson's Disease Rating Scale (mUPDRS).Results: STN DBS at [gamma] frequencies (MED and MOVE) and HF significantly improved mUPDRS scores compared to no stimulation and both [gamma] frequencies were not different from HF. DBS at [theta] and [beta] frequencies did not worsen mUPDRS scores compared to no stimulation.Conclusion: Short-term administration of STN DBS at peak dopamine-dependent or movement-related [gamma] frequencies were as effective as HF for reducing parkinsonian motor signs but DBS at [theta] and [beta] frequencies did not worsen PD motor signs.Classification of evidence: This study provides Class III evidence that STN DBS at patient-specific [gamma] frequencies and at usual high frequencies both improved mUPDRS scores compared to no stimulation and did not differ in effect.GLOSSARY: BG: basal gangliaDBS: deep brain stimulationHF: high frequencyLFP: local field potentialMED: medication-dependent peak frequenciesMOVE: movement-related peak frequenciesmUPDRS: motor Unified Parkinson's Disease Rating ScalePD: Parkinson diseasermANOVA: repeated-measures analysis of varianceSTN: subthalamic nucleusTEED: total electrical energy deliveredVT: ventral thalamus(C)2012 American Academy of Neurology

Objective: To determine whether unobtrusive long-term in-home assessment of walking speed and its variability can distinguish those with mild cognitive impairment (MCI) from those with intact cognition.Methods: Walking speed was assessed using passive infrared sensors fixed in series on the ceiling of the homes of elderly individuals participating in the Intelligent Systems for Assessing Aging Change (ISAAC) cohort study. Latent trajectory models were used to analyze weekly mean speed and walking speed variability (coefficient of variation [COV]).Results: ISAAC participants living alone included 54 participants with intact cognition, 31 participants with nonamnestic MCI (naMCI), and 8 participants with amnestic MCI at baseline, with a mean follow-up of 2.6 +/- 1.0 years. Trajectory models identified 3 distinct trajectories (fast, moderate, and slow) of mean weekly walking speed. Participants with naMCI were more likely to be in the slow speed group than in the fast (p = 0.01) or moderate (p = 0.04) speed groups. For COV, 4 distinct trajectories were identified: group 1, the highest baseline and increasing COV followed by a sharply declining COV; groups 2 and 3, relatively stable COV; and group 4, the lowest baseline and decreasing COV. Participants with naMCI were more likely to be members of either highest or lowest baseline COV groups (groups 1 or 4), possibly representing the trajectory of walking speed variability for early- and late-stage MCI, respectively.Conclusion: Walking speed and its daily variability may be an early marker of the development of MCI. These and other real-time measures of function may offer novel ways of detecting transition phases leading to dementia.GLOSSARY: aMCI: amnestic mild cognitive impairmentBIC: Bayesian information criteriaCIRS: Cumulative Illness Rating ScaleCOV: coefficient of variationFAQ: Functional Activities QuestionnaireISAAC: Intelligent Systems for Assessing Aging ChangeMCI: mild cognitive impairmentnaMCI: nonamnestic mild cognitive impairmentUPDRS: Unified Parkinson's Disease Rating ScaleWAIS: Wechsler Adult Intelligence ScaleWMH: white matter hyperintensity(C)2012 American Academy of Neurology

Objective: To assess progesterone treatment of intractable seizures in women with partial epilepsy.Methods: This randomized, double-blind, placebo-controlled, phase III, multicenter, clinical trial compared the efficacy and safety of adjunctive cyclic natural progesterone therapy vs placebo treatment of intractable seizures in 294 subjects randomized 2:1 to progesterone or placebo, stratified by catamenial and noncatamenial status. It compared treatments on proportions of >=50% responders and changes in seizure frequency from 3 baseline to 3 treated menstrual cycles.Results: There was no significant difference in proportions of responders between progesterone and placebo in the catamenial and noncatamenial strata. Prespecified secondary analysis showed that the level of perimenstrual seizure exacerbation (C1 level) was a significant predictor of responders for progesterone but not placebo. With increasing C1 levels, responders increased from 21% to 57% with progesterone vs 19% to 20% with placebo. Reductions in seizure frequency correlated with increasing C1 levels for progesterone but not placebo, progressing from 26% to 71% for progesterone vs 25% to 26% for placebo. A prespecified clinically important separation between progesterone and placebo responders (37.8% vs 11.1%; p = 0.037) was realized among 21.4% of women who had C1 level >=3.Conclusion: There was no difference in the primary outcome of >=50% responder rates between progesterone vs placebo for catamenial or noncatamenial groups. Post hoc findings suggest that the level of perimenstrual seizure exacerbation is a significant predictor of responder rate with progesterone and that progesterone may provide clinically important benefit for a subset of women with perimenstrually exacerbated seizures.Classification of evidence: This study provides Class III evidence that cyclic progesterone is ineffective in women with intractable partial epilepsy. Post hoc analysis identified a subset of women with higher levels of perimenstrual seizure exacerbation that were responsive to treatment.GLOSSARY: ADSF: average daily seizure frequencyAED: antiepileptic drugCPS: complex partial seizuresMSST: most severe seizure typeSAE: serious adverse eventSGMS: secondary generalized motor seizuresSPS: simple partial seizures.(C)2012 American Academy of Neurology

Objective: To update the 2004 American Academy of Neurology/Child Neurology Society practice parameter on treatment of infantile spasms in children.Methods: MEDLINE and EMBASE were searched from 2002 to 2011 and searches of reference lists of retrieved articles were performed. Sixty-eight articles were selected for detailed review; 26 were included in the analysis. Recommendations were based on a 4-tiered classification scheme combining pre-2002 evidence and more recent evidence.Results: There is insufficient evidence to determine whether other forms of corticosteroids are as effective as adrenocorticotropic hormone (ACTH) for short-term treatment of infantile spasms. However, low-dose ACTH is probably as effective as high-dose ACTH. ACTH is more effective than vigabatrin (VGB) for short-term treatment of children with infantile spasms (excluding those with tuberous sclerosis complex). There is insufficient evidence to show that other agents and combination therapy are effective for short-term treatment of infantile spasms. Short lag time to treatment leads to better long-term developmental outcome. Successful short-term treatment of cryptogenic infantile spasms with ACTH or prednisolone leads to better long-term developmental outcome than treatment with VGB.Recommendations: Low-dose ACTH should be considered for treatment of infantile spasms. ACTH or VGB may be useful for short-term treatment of infantile spasms, with ACTH considered preferentially over VGB. Hormonal therapy (ACTH or prednisolone) may be considered for use in preference to VGB in infants with cryptogenic infantile spasms, to possibly improve developmental outcome. A shorter lag time to treatment of infantile spasms with either hormonal therapy or VGB possibly improves long-term developmental outcomes.GLOSSARY: AAN: American Academy of NeurologyACTH: adrenocorticotropic hormoneAE: adverse effectAED: antiepileptic drugBD: Breslow-DayCI: confidence intervalERG: electroretinogramFDA: Food and Drug AdministrationIVIg: IV immunoglobulinLEV: levetiracetamNZP: nitrazepamOR: odds ratioRCT: randomized controlled trialTPM: topiramateTRH: thyrotropin-releasing hormoneTSC: tuberous sclerosis complexUKISS: United Kingdom Infantile Spasms StudyVABS: Vineland Adaptive Behavioral ScaleVGB: vigabatrinVPA: valproic acidZNS: zonisamide(C)2012 American Academy of Neurology

Objective: To describe the clinical characteristics of encounters with patients misdiagnosed with multiple sclerosis (MS).Methods: A cross-sectional Internet-based physician survey of MS specialists was performed.Results: The response rate for the survey was 50.4%. Of those who responded, the majority (95%) reported having evaluated 1 or more patients who had been diagnosed with MS, but who they strongly felt did not have MS, within the last year. The majority of respondents (>90%) also reported the use of disease-modifying therapy in a proportion of these patients. Most respondents (94%) found clinical encounters with these patients equally or more challenging than giving a new diagnosis of MS. Fourteen percent of respondents reported that they did not always inform such patients of their opinion that they did not have MS.Conclusions: The misdiagnosis of MS is common and has significant consequences for patient care and health care system costs. Caring for a patient with a misdiagnosis of MS is challenging, and at times honest disclosure of a misdiagnosis represents an important ethical concern for neurologists. More data are needed on this patient population to improve diagnostic acumen and the care of these patients.GLOSSARY: DMT: disease-modifying therapyMS: multiple sclerosis(C)2012 American Academy of Neurology