Neurology October 2009 Volume 73 Issue 17

Objective: Chronic inflammatory demyelinating polyneuropathy (CIDP) is characterized by immune-mediated peripheral demyelination. Although corticosteroid, IV immunoglobulin (IVIg) and plasma exchange have been established as the most effective therapeutics, subpopulations of patients show little or no response to either of these therapies. In this study, we examined whether particular genetic factors influence the therapeutic responsiveness of patients with CIDP.Methods: One hundred Japanese patients categorized as responders or nonresponders to IVIg therapy participated in our study. We performed an association analysis with single nucleotide polymorphisms (SNPs) and haplotype studies between the IVIg responders and nonresponders.Results: Two separate SNPs, corresponding to TAG-1 (transient axonal glycoprotein 1) and CLEC10A (C-type lectin domain family 10, member A), showed strong significant differences between responders and nonresponders. Haplotype analysis of a series of expanded SNPs, from TAG-1 or CLEC10A, showed that only TAG-1 included a significant haplotype within 1 linkage disequilibrium block, which accommodates IVIg responsiveness. Diplotype analysis of TAG-1 also supported this observation.Conclusions: Transient axonal glycoprotein 1 is a crucial molecule involved in IV immunoglobulin responsiveness in Japanese patients with chronic inflammatory demyelinating polyneuropathy.(C)2009AAN Enterprises, Inc.

Background: Previous epidemiologic studies indicate that diabetes mellitus (DM) is associated with cognitive decline and an increased risk of developing Alzheimer disease (AD) in people who do not have dementia. However, little is known about the effect of DM on the rate of cognitive decline in established AD. Our objective was to determine whether DM influences the rate of cognitive decline in patients with AD.Methods: A total of 608 patients with a probable diagnosis of AD and a Mini-Mental State Examination (MMSE) score between 10 and 26 were enrolled in a prospective multicenter study. Participants were followed up to 52 (mean 26) months. DM was assessed at baseline (history of DM or antidiabetic medication use). Cognitive function was assessed twice yearly with the MMSE.Results: Sixty-three participants (10.4%) had DM at baseline. In a mixed model adjusted for sex, age, educational level, dementia severity, cholinesterase inhibitor use, and vascular factors (hypertension, atrial fibrillation, coronary heart disease, and hypercholesterolemia), there were no differences between the groups in MMSE baseline scores (-0.75, p = 0.20), but cognitive decline was slower in the group with DM (0.38, p = 0.01).Conclusions: In a cohort of community-dwelling patients with Alzheimer disease (AD), the presence of diabetes mellitus (DM) was associated with a lower rate of cognitive decline. Future studies will need to address the potential impact of DM in the cerebral aging process and to assess the neuropathologic variations in patients with AD with DM.(C)2009AAN Enterprises, Inc.

Background: Eighteen patients with severe and refractory Tourette syndrome (TS) underwent bilateral thalamic deep brain stimulation (DBS).Objective: To assess the long-term outcome on tics, behavioral symptoms, and cognitive functions in the largest case series of thalamic DBS for TS to date.Methods: In this prospective cohort study, 15 of the original 18 patients were evaluated before and after surgery according to a standardized protocol that included both neuropsychiatric and neuropsychological assessments.Results: In addition to marked reduction in tic severity (p = 0.001), 24-month follow-up ratings showed improvement in obsessive-compulsive symptoms (p = 0.009), anxiety symptoms (p = 0.001), depressive symptoms (p = 0.001), and subjective perception of social functioning/quality of life (p = 0.002) in 15 of 18 patients. There were no substantial differences on measures of cognitive functions before and after DBS.Conclusions: At 24-month follow-up, tic severity was improved in patients with intractable Tourette syndrome (TS) who underwent bilateral thalamic deep brain stimulation. Available data from 15 of 18 patients also showed that neuropsychiatric symptoms were improved and cognitive performances were not disadvantaged. Controlled studies on larger cohorts with blinded protocols are needed to verify that this procedure is effective and safe for selected patients with TS.Level of evidence: This study provides class IV evidence that bilateral thalamic deep brain stimulation reduces global tic severity measured 24 months after implantation in patients with severe intractable Tourette syndrome.(C)2009AAN Enterprises, Inc.

Objective: We prospectively evaluated the fluctuation of lamotrigine (LTG) clearance during the menstrual cycle. We also assessed the effect of postmenopausal status and investigated in detail the effect of oral contraceptives (OCs) on LTG clearance.Methods: Three groups of women with epilepsy using LTG monotherapy were evaluated. Women in the first group (n = 7) had a regular cycle and did not use OCs; the second group used a 1-phase combined OC (n = 7), and the third group (n = 7) was postmenopausal. Two menstrual cycles or at least 2 months (postmenopausal women) were assessed, monitoring LTG levels every other day.Results: The mean apparent LTG clearance in women of reproductive age not using OCs was 49 (SD 22.6, range 20.4-83.5) L/24 hours. No significant effect of endogenous hormones on LTG clearance was found. In women using OCs, the mean LTG clearance was 126 (SD 60.2, range 44.3-205) L/24 hours. There was an increase in LTG levels during the pill-free week, with maximum levels 54% (range 29%-129%) higher than baseline levels. LTG levels decreased to the baseline value within a mean of 8 days of starting OC use (SD 3.7, range 2.5-16.5). In the postmenopausal women, the mean clearance was 82 (SD 38.4, range 35.9-125) L/24 hours.Conclusions: We observed a higher mean lamotrigine (LTG) clearance in postmenopausal women compared with young women not using oral contraceptives (OCs) and confirmed that OC use may have a strong effect on LTG clearance. There was no significant fluctuation of LTG clearance during the menstrual cycle.(C)2009AAN Enterprises, Inc.

Background: Dengue infection is caused by a flavivirus, with 4 virus serotypes (types 1 to 4). The serotypes 2 and 3 represent the principal agents related to nervous system involvement. Neurologic involvement occurs in 4%-5% of dengue infection cases. The major mechanisms of the disease may be related to direct viral infection or postinfectious autoimmune process. The detection of intrathecal synthesis of specific antibodies has been used to support neurologic diagnosis as a proof of local reaction. It may be quantitatively calculated by the specific antibody index.Objectives: To determine if patients with neurologic manifestations associated with dengue produce specific antibodies in the CNS and to determine the antibodies' clinical and pathophysiologic relevance.Methods: CSF and serum were evaluated for dengue immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies by ELISA and for intrathecal synthesis of IgG antibodies to the dengue virus. Subjects included 10 patients IgM seropositive for dengue virus diagnosed with myelitis, encephalitis, optic neuromyelitis, or Guillain-Barre syndrome.Results: All patients had IgG and IgM antibodies to dengue virus in their sera; 7 were IgM positive and 9 were IgG positive for dengue virus in CSF. Only the 3 patients with myelitis had intrathecal synthesis of specific IgG antibodies.Conclusions: Intrathecal synthesis of antibodies to dengue virus occurs in the CNS. It may be used as a marker of myelitis associated with dengue, and it seems to be related to the pathogenesis of spinal cord disease due to direct viral invasion.(C)2009AAN Enterprises, Inc.