Neurology March 2009 Volume 72 Issue 11

Objective: Associations between peripheral neuropathy and restless legs syndrome (RLS) have been described, but have not been consistently reproduced. If RLS prevalence is truly increased by neuropathy, this has important implications for RLS pathophysiology.Methods: In a case-control design, 245 patients with peripheral neuropathy and 245 age- and sex-matched controls were screened for RLS using a standardized phone questionnaire based on international RLS diagnostic criteria. All persons who answered yes to three of four criteria were considered screen-positive. All screen-positive patients underwent a confirmatory diagnostic evaluation by a movement disorders specialist blinded to the neuropathy status of the patient. RLS prevalence was calculated and compared using Fisher exact test.Results: A total of 65 (26.5%) patients with neuropathy screened positive compared to 25 (10.2%) controls (p < 0.0001). However, the diagnosis was confirmed in only 46% of screen-positive patients with neuropathy, vs 80% of controls (p = 0.005). Cramps and paresthesia without true diurnal variation or rest exacerbation were the commonest causes of false-positive screens. After diagnostic confirmation, the overall prevalence of RLS did not differ between neuropathy patients and controls (12.2% vs 8.2%, p = 0.14). However, when classified by etiology, RLS was found in 14/72 (19.4%) patients with hereditary neuropathy, a prevalence higher than found in controls (p = 0.016) and acquired neuropathy (9.2%, p = 0.033). Among patients with neuropathy, those with RLS more commonly had a family history of RLS (37% vs 15%, p = 0.007) and were younger (49.9 vs 61.4, p = 0.0003).Conclusions: Restless legs syndrome is more prevalent among patients with hereditary neuropathy, but not in those with acquired neuropathies.GLOSSARY: CIDP = chronic inflammatory demyelinating polyneuropathy; GBS = Guillain-Barre syndrome; HMSN = hereditary motor sensory neuropathy; HSAN = hereditary sensory and autonomic neuropathy; IRLSSG = International Restless Legs Study Group; MGUS = monoclonal gammopathy of uncertain significance; NCS = nerve conduction studies; PPV = positive predictive value; RLS = restless legs syndrome.(C)2009AAN Enterprises, Inc.

Background: Acute disseminated encephalomyelitis (ADEM) is typically a monophasic demyelinating disorder. However, a clinical presentation consistent with ADEM can also be the first manifestation of multiple sclerosis (MS), particularly in children. Quantitative analyses of MRI images from children with monophasic ADEM have yet to be compared with those from children with MS, and MRI criteria capable of distinguishing ADEM from MS at onset have yet to be derived.Methods: A retrospective analysis of MRI scans obtained at first attack from 28 children subsequently diagnosed with MS and 20 children with ADEM was performed. T2/fluid-attenuated inversion recovery hyperintense lesions were quantified and categorized according to location, description, and size. T1-weighted images before and after administration of gadolinium were evaluated for the presence of black holes and for gadolinium enhancement. Mean lesion counts and qualitative features were compared between groups and analyzed to create a proposed diagnostic model.Results: Total lesion number did not differentiate ADEM from MS, but periventricular lesions were more frequent in children with MS. Combined quantitative and qualitative analyses led to the following criteria to distinguish MS from ADEM: any two of 1) absence of a diffuse bilateral lesion pattern, 2) presence of black holes, and 3) presence of two or more periventricular lesions. Using these criteria, MS patients at first attack could be distinguished from monophasic ADEM patients with an 81% sensitivity and a 95% specificity.Conclusions: MRI diagnostic criteria are proposed that may be useful in differentiating children experiencing the first attack of multiple sclerosis from those with monophasic acute disseminated encephalomyelitis.(C)2009AAN Enterprises, Inc.

Objective: High-frequency oscillations (HFOs) can be recorded in epileptic patients with clinical intracranial EEG. HFOs have been associated with seizure genesis because they occur in the seizure focus and during seizure onset. HFOs are also found interictally, partly co-occurring with epileptic spikes. We studied how HFOs are influenced by antiepileptic medication and seizure occurrence, to improve understanding of the pathophysiology and clinical meaning of HFOs.Methods: Intracerebral depth EEG was partly sampled at 2,000 Hz in 42 patients with intractable focal epilepsy. Patients with five or more usable nights of recording were selected. A sample of slow-wave sleep from each night was analyzed, and HFOs (ripples: 80-250 Hz, fast ripples: 250-500 Hz) and spikes were identified on all artifact-free channels. The HFOs and spikes were compared before and after seizures with stable medication dose and during medication reduction with no intervening seizures.Results: Twelve patients with five to eight nights were included. After seizures, there was an increase in spikes, whereas HFO rates remained the same. Medication reduction was followed by an increase in HFO rates and mean duration.Conclusions: Contrary to spikes, high-frequency oscillations (HFOs) do not increase after seizures, but do so after medication reduction, similarly to seizures. This implies that spikes and HFOs have different pathophysiologic mechanisms and that HFOs are more tightly linked to seizures than spikes. HFOs seem to play an important role in seizure genesis and can be a useful clinical marker for disease activity.GLOSSARY: AED = antiepileptic drug; CBZ = carbamazepine; CLOB = clobazam; FR = fast ripple; FR_isol = fast ripples without co-occurring spikes; FR_Sp = fast ripples with co-occurring spikes; GBP = gabapentin; HFO = high-frequency oscillation; Lai/s = left anterior inferior/superior electrode (porencephalic cyst); LEV = levetiracetam; LF/p/a = left frontal/posterior/anterior electrode; LOP = left frontal operculum electrode; Lpi/s = left posterior inferior/superior electrode; L/RA = left/right amygdale electrode; L/RC/a/s = left/right cingulate/anterior/superior electrode; L/RE = left/right epidural electrode; L/RH = left/right hippocampus electrode; L/ROF = left/right orbitofrontal electrode; L/RO/i/s = left/right occipital/infracalcine/supracalcine electrode; L/RP = left/right parahippocampus electrode; L/RS = left/right supramarginal gyrus electrode; LSMAa/p = left supplementary motor area anterior/posterior electrode; LT = left anteriotemporal electrode; LTG = lamotrigine; OXC = oxcarbamazepine; PRI = primidone; PTH = phenytoin; R = ripple; R_isol = ripples without co-occurring spikes; R_Sp = ripples with co-occurring spikes; SEEG = stereo-EEG; SEZ = one or more seizures; SOZ = seizure onset zone; Sp = spike; TPM = topiramate.(C)2009AAN Enterprises, Inc.

Objectives: The extent to which highly active antiretroviral therapy (HAART) era cognitive disorders are due to active processes, incomplete clearance of reservoirs, or comorbidities is controversial. This study aimed to determine if immunologic and virologic factors influence cognition after first-time HAART in Thai individuals with HIV-associated dementia (HAD) and Thai individuals without HAD (non-HAD).Methods: Variables were captured longitudinally to determine factors predictive of degree of cognitive recovery after first-time HAART. Neuropsychological data were compared to those of 230 HIV-negative Thai controls.Results: HIV RNA and CD4 lymphocyte counts were not predictive of HAD cross-sectionally or degree of cognitive improvement longitudinally. In contrast, baseline and longitudinal HIV DNA isolated from monocytes correlated to cognitive performance irrespective of plasma HIV RNA and CD4 lymphocyte counts pre-HAART (p < 0.001) and at 48 weeks post HAART (p < 0.001). Levels exceeding 3.5 log10 copies HIV DNA/106 monocyte at baseline distinguished all HAD and non-HAD cases (p < 0.001). At 48 weeks, monocyte HIV DNA was below the level of detection of our assay (10 copies/106 cells) in 15/15 non-HAD compared to only 4/12 HAD cases, despite undetectable plasma HIV RNA in 26/27 cases. Baseline monocyte HIV DNA predicted 48-week cognitive performance on a composite score, independently of concurrent monocyte HIV DNA and CD4 count (p < 0.001).Conclusions: Monocyte HIV DNA level correlates to cognitive performance before highly active antiretroviral therapy (HAART) and 48 weeks after HAART in this cohort and baseline monocyte HIV DNA may predict 48-week cognitive performance. These findings raise the possibility that short-term incomplete cognitive recovery with HAART may represent an active process related to this peripheral reservoir.(C)2009AAN Enterprises, Inc.

In this essay, we draw attention to some recent downsides and surprises of multiple sclerosis (MS) therapeutics. These include experiences with recent head-to-head trials of interferon-beta and glatiramer acetate, dose escalation trials, frustrating efforts with progressive MS trials, failures of smart concepts and designer therapies, and harsh lessons from newly observed adverse reactions.(C)2009AAN Enterprises, Inc.