Methods: A sample of 140 consecutive patients with MS were interviewed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Axis I disorders (SCID-IV) from which details of cannabis use were recorded. Cognition was assessed using the Neuropsychological Battery for MS supplemented with the Symbol Digit Modalities Test (SDMT), an index of information processing speed, working memory, and sustained attention.

Results: Ten subjects (7.7%) were defined as current cannabis users based on use within the last month. Compared to non-cannabis users (n = 130), they were younger (p = 0.001). Each of the 10 current cannabis users was matched on demographic and disease variables to four subjects with MS who did not use cannabis (total control sample n = 40). Group comparisons revealed that the proportion of patients meeting DSM-IV criteria for a psychiatric diagnosis was higher in cannabis users (p = 0.04). In addition, on the SDMT, cannabis users had a slower mean performance time (p = 0.006) and a different pattern of response compared to matched controls (group x time interaction; p = 0.001).

Conclusions: Inhaled cannabis is associated with impaired mentation in patients with multiple sclerosis, particularly with respect to cognition. Future studies are required to clarify the direction of this relationship.

GLOSSARY: 7/24 = 7/24 Spatial Learning Test; BSS = Beck Suicide Scale; COWAT = Controlled Oral Word Association Test; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders; EDSS = Expanded Disability Status Scale; HADS = Hospital Anxiety and Depression Scale; MS = multiple sclerosis; NPBMS = Neuropsychological Battery for MS; PASAT = Paced Auditory Serial Addition Task; SCID-IV = Structured Clinical Interview for DSM-IV Axis I disorders; SDMT = Symbol Digit Modalities Test; SRT = Selective Reminding Test; SSSI = Social Stress and Support Inventory.

Methods: A prospective, multicenter study of the consequences of FSE included children, aged 1 month through 5 years, presenting with a febrile seizure lasting 30 minutes or more. Procedures included neurologic history and examination and an MRI and EEG within 72 hours. All information related to seizure semiology was reviewed by three epileptologists blinded to MRI and EEG results and to subsequent outcome. Inter-rater reliability was assessed by the statistic.

Results: Among 119 children, the median age was 1.3 years, the mean peak temperature was 103.2°F, and seizures lasted a median of 68.0 minutes. Seizure duration followed a Weibull distribution with a shape parameter of 1.68. Seizures were continuous in 52% and behaviorally intermittent (without recovery in between) in 48%; most were partial (67%) and almost all (99%) were convulsive. In one third of cases, FSE was unrecognized in the emergency department. Of the 119 children, 86% had normal development, 24% had prior febrile seizures, and family history of febrile seizures in a first-degree relative was present in 25%.

Conclusions: Febrile status epilepticus is usually focal and often not well recognized. It occurs in very young children and is usually the first febrile seizure. Seizures are typically very prolonged and the distribution of seizure durations suggests that the longer a seizure continues, the less likely it is to spontaneously stop.

GLOSSARY: ED = emergency department; FS = febrile seizures; FSE = febrile status epilepticus; HHV = human herpesvirus; ILAE = International League Against Epilepsy; IQR = interquartile range; MTLE = mesial temporal lobe epilepsy; MTS = mesial temporal sclerosis.

Methods: Sequence analysis of the KCNQ2, Q3, and Q5 coding regions was performed in a screening sample consisting of 58 nuclear families with rolandic epilepsy. Subsequently, an association study was conducted for all discovered variants in a case–control sample comprising 459 German patients with idiopathic generalized epilepsy (IGE) and 462 population controls.

Results: An in-frame deletion of codon 116 in KCNQ2 (p.Lys116del) and a missense mutation in KCNQ3 (p.Glu299Lys) were detected in two index cases exhibiting rolandic epilepsy and benign neonatal convulsions. Both mutations resulted in reduced potassium current amplitude in Xenopus oocytes. Mutation analysis of families with rolandic epilepsy without neonatal seizures discovered three novel missense variations (KCNQ2 p.Ile592Met, KCNQ3 p.Ala381Val, KCNQ3 p.Pro574Ser). The KCNQ2 p.Ile592Met variant displayed a significant reduction of potassium current amplitude in Xenopus oocytes and was present only once in 552 controls. Both missense variants identified in KCNQ3 (p.Ala381Val and p.Pro574Ser) were present in all affected family members and did not occur in controls, but did not show obvious functional abnormalities. The KCNQ3 missense variant p.Pro574Ser was also detected in 8 of 455 IGE patients but not in 454 controls (p = 0.008). In KCNQ2, a silent single nucleotide polymorphism (rs1801545) was found overrepresented in both epilepsy samples (IGE, p = 0.004).

Conclusion: Sequence variations of the KCNQ2 and KCNQ3 genes may contribute to the etiology of common idiopathic epilepsy syndromes.

GLOSSARY: BNFC = benign neonatal familial convulsions; bp = base pair; cRNA = complementary RNA; IAE = idiopathic absence epilepsy; IE = idiopathic epilepsy; IGE = idiopathic generalized epilepsy; JME = juvenile myoclonic epilepsy; OR = odds ratio; RE = rolandic epilepsy; SNP = single nucleotide polymorphism; WT = wild type.

Methods: One hundred five patients with acute left hemisphere ischemic stroke had diffusion-weighted imaging, perfusion-weighted imaging, a test of picture naming, and other language tests at admission and 2 to 4 days later. Linear regression was used to determine whether diffusion–perfusion mismatch in any BA in language cortex, total volume of mismatch, or diffusion or perfusion abnormality predicted degree of improvement in naming by days 3 to 5.

Results: The presence of >20% diffusion–perfusion mismatch in left BA 37 and total volumes of diffusion and perfusion abnormality at day 1 each independently predicted degree of improvement in naming. Mismatch in this area did not predict the degree of improvement in other language tests or the NIH Stroke Scale in this study.

Conclusions/Relevance: Diffusion–perfusion mismatch in left Brodmann area 37 was strongly associated with acute improvement in naming, independently of volume or percentage of total mismatch or diffusion or perfusion abnormality. These data indicate that mismatch in a particular area is a marker of salvageable tissue and an important predictor of potential for recovery of functions that depend on that area. Location of mismatch before treatment may help to predict potential benefits of reperfusion.

GLOSSARY: ADC = apparent diffusion coefficient; BA = Brodmann area; DWI = diffusion-weighted imaging; NIHSS = NIH Stroke Scale; PWI = perfusion-weighted imaging; TE = echo time; TR = repetition time; TTP = time to peak.

Methods: We studied 100 consecutive patients with ischemic stroke with MCA occlusions on prebolus transcranial Doppler (TCD) examination treated with tPA following SITS-MOST criteria. MetS was diagnosed following AHA/NHLBI-2005 criteria. Resistance to thrombolysis was defined as the absence of TCD-assessed complete MCA recanalization 24 hours after tPA infusion. Infarct volume was measured on CT scans. Long-term clinical outcome was evaluated by the modified Rankin scale (mRS) score at day 90.

Results: Fifty-eight (58%) patients fulfilled MetS criteria. Median prebolus NIH Stroke Scale score was 17. Forty (42%) patients showed resistance to clot dissolution, and 53 (53%) had poor clinical outcomes (mRS > 2). A multivariable-adjusted logistic regression model identified MetS as independently associated with resistance to thrombolysis (OR 4.7, 95% CI [1.7–13.6], p = 0.004). In the whole sample, MetS was associated with mRS > 2 (OR 2.4 [1.1–5.4], p = 0.03), although this association was no longer significant after multivariable adjustment. However, in patients with atherothrombotic stroke, MetS emerged as an independent predictor of poor long-term outcome (adjusted OR 13.9 [1.3–148.7], p = 0.02).

Conclusion: In our series, the metabolic syndrome was associated with a poor response to thrombolysis in patients with acute middle cerebral artery occlusions, as reflected by a higher resistance to clot dissolution.

GLOSSARY: AHA/NHLBI = American Heart Association & National Heart, Lung and Blood Institute; BMI = body mass index; HDL = high-density lipoprotein; MCA = middle cerebral artery; MetS = metabolic syndrome; mRS = modified Rankin scale; NIHSS = National Institutes of Health Stroke Scale; TCD = transcranial Doppler; TIBI = Thrombolysis in Brain Ischemia; tPA = tissue-type plasminogen activator.

Objective: To investigate whether the reactivities of anti-GD1b IgG to such complexes are different between ataxic and nonataxic patients.

Methods: The authors examined sera from 17 patients with GBS (9 with ataxia and 8 without ataxia) who had GD1b-mono IgG, with the use of an ELISA in which wells were coated with a mixture of GD1b and each of nine gangliosides (GM1, GM2, GM3, GD1a, GD3, GT1a, GT1b, GQ1b, and GalNAc-GD1a). The binding activities of the anti-GD1b IgG antibodies against such mixture antigens were compared between ataxic and nonataxic patients.

Results: The reactivities to antigens, such as GD1b combined with GD1a, GT1b, GQ1b, and GalNAc-GD1a, were significantly reduced in ataxic compared with nonataxic patients. Sera from all nonataxic patients had antibody activities to GSCs not containing GD1b.

Conclusions: The addition of another ganglioside may cause conformational change of GD1b. Given the inhibition of the binding ability of the anti-GD1b IgG antibodies by such a conformational change, the anti-GD1b IgG antibodies in ataxic patients may interact closely with GD1b. IgG antibodies highly specific for GD1b may induce ataxia in Guillain-Barré syndrome.

GLOSSARY: GBS = Guillain-Barré syndrome; GSCs = ganglioside complexes; OD = optical density.

Objective: This prospective, randomized, double-blinded, placebo-controlled trial evaluated the safety and effectiveness of a surgically implanted shunt in subjects with probable AD.

Methods: A total of 215 subjects with probable AD by National Institute of Neurological Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association criteria received either a low-flow ventriculoperitoneal shunt or a sham (occluded) shunt for 9 months. Longitudinal CSF sampling was performed in both active and control subjects. Primary outcome measures were the Mattis Dementia Rating Scale and the Global Deterioration Scale. CSF Aβ_(1-42) and MAP- also were assayed.

Results: After a planned interim analysis, the study was halted for futility. Using the intent-to-treat population, no between-group differences were observed in the primary outcome measures. The surgical procedure and device were associated with 12 CNS infections, some temporally associated with CSF sampling. All were treated successfully.

Conclusions: We found no benefit to low-flow CSF shunting in subjects with mild to severe Alzheimer disease. CSF infections, while treatable, occurred more frequently than expected, in some cases likely related to CSF sampling.

GLOSSARY: Aβ = amyloid beta-peptides; AD = Alzheimer disease; ADCS-ADL = AD Cooperative Study Activities of Daily Living; BBB = blood–brain barrier; CP = choroid plexus; FDA = Food and Drug Administration; GDS = Global Deterioration Scale; GEE = Generalized Estimating Equations; IA = interim analysis; ISF = interstitial fluid; ITT = intent-to-treat; LRP-1 = lipoprotein receptor-related protein-1; MAP- = microtubule-associated-protein tau; MDRS = Mattis Dementia Rating Scale; MMSE = Mini-Mental State Examination; NAART = North American Adult Reading Test; NINCDS-ADRDA = National Institutes of Neurological and Communicative Diseases and Stroke–Alzheimer’s Disease and Related Disorders Association; NPH = normal-pressure hydrocephalus; PHF = perihippocampal fissures; RAGE = receptor for advanced glycation end-products; SADAS-Cog = Standardized AD Assessment Scale–Cognitive; SAE = serious adverse events.

Background: In normal aging physical fitness appears to mitigate functional and structural age-related brain changes. Whether this is observed in AD is not known.

Methods: Subjects without dementia (n = 64) and subjects with early-stage AD (n = 57) had MRI and standard clinical and psychometric evaluations. Peak oxygen consumption (VO₂^peak), the standard measure of cardiorespiratory fitness, was assessed during a graded treadmill test. Normalized whole brain volume, a brain atrophy estimate, was determined by MRI. Pearson correlation and linear regression were used to assess fitness in relation to brain volume and cognitive performance.

Results: Cardiorespiratory fitness (VO₂^peak) was modestly reduced in subjects with AD (34.7 [5.0] mL/kg/min) vs subjects without dementia (38.1 [6.3] mL/kg/min, p = 0.002). In early AD, VO₂^peak was associated with whole brain volume (beta = 0.35, p = 0.02) and white matter volume (beta = 0.35, p = 0.04) after controlling for age. Controlling for additional covariates of sex, dementia severity, physical activity, and physical frailty did not attenuate the relationships. VO₂^peak was associated with performance on delayed memory and digit symbol in early AD but not after controlling for age. In participants with no dementia, there was no relationship between fitness and brain atrophy. Fitness in participants with no dementia was associated with better global cognitive performance (r = 0.30, p = 0.02) and performance on Trailmaking A and B, Stroop, and delayed logical memory but not after controlling for age.

Conclusions: Increased cardiorespiratory fitness is associated with reduced brain atrophy in Alzheimer disease (AD). Cardiorespiratory fitness may moderate AD-related brain atrophy or a common underlying AD-related process may impact both brain atrophy and cardiorespiratory fitness.

GLOSSARY: AD = Alzheimer disease; CDR = Clinical Dementia Rating; MMSE = Mini-Mental State Examination; PASE = Physical Activity Scale in the Elderly.