Methods: We conducted a retrospective review of 2,477 patients with definite relapsing-onset MS followed until July 2003 in British Columbia, Canada. Time-dependent Cox proportional hazards models examined the effect of relapses at different time periods (0–5; >5–10; >10 years postonset) on time to cane (Expanded Disability Status Scale [EDSS]) and secondary progressive MS (SPMS). Findings were derived from hazard ratios with 95% confidence intervals (CIs), adjusted for sex, onset age, and symptoms.

Results: Mean follow-up was 20.6 years; 11,722 postonset relapses were recorded. An early relapse (within 5 years postonset) was associated with an increased hazard in disease progression over the short term, by 48%; 95% CI 37%–60% for EDSS 6 and 29%; 95% CI 20%–38% for SPMS. However, this substantially lessened to 10%; 95% CI 4%–16% (EDSS 6) and 2%; 95% CI –2%–7% (SPMS) after 10 years postonset. The impact of later relapses (>5–10 years postonset) also lessened over time. Effects were modulated by age, impact being greatest in younger (<25 years at onset) and least in older (≥35 years) patients where relapses beyond 5–years postonset typically failed to reach significance. Relapses during SPMS had no measurable impact on time to EDSS 6 from SPMS.

Conclusion: Relapses within the first 5 years of disease impacted on disease progression over the short term. However, the long-term impact was minimal, either for early or later relapses. Long-term disease progression was least affected by relapses in patients with an extended disease duration (>10 years) or already in the secondary progressive phase.

Methods: In this longitudinal correlational research study, 75 patients with relapsing-remitting MS (48 women and 27 men, mean age 36 years, mean disease duration 5 years, mean Expanded Disability Status Scale [EDSS] 1.7) without clinical signs of a relapse underwent 2 MRI measurements (number and volume of T1 contrast-enhancing lesions and of T2 lesions) and clinical examinations (EDSS and Multiple Sclerosis Functional Composite [MSFC]) with a mean interscan interval of 10 weeks. Patients were divided into 3 groups: A (n = 38), Gd on 1 scan; B (n = 12), Gd on both scans; and C (n = 25), Gd on neither scan.

Results: In group A, PASAT was better at the Gd-negative time point (p = 0.002), whereas the other MSFC subscores remained unchanged. Subgroup analysis confirmed the finding in patients with a Gd-positive scan first, whereas this was not the case for patients with a Gd-negative scan first, presumably owing to the small sample size of this subgroup. In groups B and C, there was no difference between both time points regarding MSFC and its subscores. EDSS remained stable in all groups during the investigation.

Conclusions: Paced Auditory Serial Addition Test performance is affected by the appearance of Gd enhancement as surrogate marker of inflammatory activity in otherwise physically stable patients with multiple sclerosis, which may indicate that Gd enhancement causes a diffuse impairment of cerebral connectivity with a negative impact on cognitive functioning.

Methods: We investigated 8 patients with the limited form of NMO with myelitis in comparison with 9 patients with the definite form.

Result: All patients with limited and definite form showed uniform relapsing-remitting courses, with no secondary progressive courses. Pathologic findings of biopsy specimens from the limited form were identical to those of autopsy from the definite form, demonstrating extremely active demyelination of plaques, extensive loss of AQP4 immunoreactivity in plaques, and diffuse infiltration by macrophages containing myelin basic proteins with thickened hyalinized blood vessels. Moreover, the definite form at the nadir of relapses displayed significantly higher amounts of the inflammatory cytokines interleukin (IL)-1β and IL-6 in CSF than the limited form and multiple sclerosis.

Conclusion: This consistency of pathologic findings and uniformity of courses indicates that aquaporin 4–specific autoantibodies as the initiator of the neuromyelitis optica (NMO) lesion consistently play an important common role in the pathogenicity through the entire course, consisting of both limited and definite forms, and NMO continuously displays homogeneity of pathogenic effector immune mechanisms through terminal stages, whereas multiple sclerosis should be recognized as the heterogeneous 2-stage disease that could switch from inflammatory to degenerative phase. This report is a significant description comparing the pathologic and immunologic data of limited NMO with those of definite NMO.

Methods: We retrospectively examined 237 consecutive acute ischemic stroke patients who underwent MRI within 24 hours and follow-up MRI during the week after symptom onset. We defined new MBs as MBs that newly appeared on follow-up GRE outside the infarcted area. We examined the association of new MBs with demographics, risk factors, laboratory data, baseline MBs, and small vessel disease (SVD; leukoaraiosis and lacunar infarctions).

Results: Seventy-five patients (31.6%) had baseline MBs, and 30 (12.7%) developed new MBs. Multiple logistic regression analysis indicated that the presence of baseline MBs (odds ratio [OR] 5.72, 95% confidence interval [CI] 2.12–15.42, p = 0.001) and severe SVD (OR 2.94, 95% CI 1.12–7.77, p = 0.03) independently predicted the development of new MBs. Of the 56 new MBs, 29 (51.8%) appeared in the lobar location, 17 (30.4%) appeared in the deep location, and 10 (17.9%) appeared in the infratentorial location.

Conclusions: This study suggests that new microbleeds (MBs) can develop rapidly after acute ischemic stroke. Baseline MBs and severe small vessel disease are predictors for the development of new MBs. Further studies will be needed to investigate the clinical implications and mechanisms of these findings.

Methods: We retrospectively examined consecutive acute ischemic stroke patients who underwent gradient echo MRI. The presence of cerebral microbleeds on gradient echo MRI was independently interpreted. The number and location of microbleeds were assessed. Demographics including age, sex, risk factors, and stroke subtype were obtained. Kidney function was estimated by measuring glomerular filtration rate (GFR) with the modification of diet in renal disease method.

Results: Of the 152 patients included, 45 (29.6%) patients had cerebral microbleeds on gradient echo MRI. The cerebral microbleeds were most commonly located in deep or infratentorial location (27/45 [60%]). Hypertension, presence of leukoaraiosis, old age, and low GFR were associated with the presence of cerebral microbleeds (p = 0.064, <0.001, 0.014, and <0.001). The mean GFR levels were lower in patients with cerebral microbleeds (65.15 ± 22.54 vs 78.82 ± 19.11 mL/min/1.73 m²). After the adjustment of risk factors, age, and sex, low GFR levels were associated with the presence of cerebral microbleeds (odds ratio, 3.85; 95% confidence interval, 1.52 to 9.76, p = 0.004).

Conclusion: Impaired kidney function is associated with the presence of cerebral microbleeds in acute ischemic stroke.

Methods: Twenty-six subjects with a family history of FAD were divided into 2 subgroups according to genotype (FAD mutation carriers, n = 15; FAD noncarriers, n = 11). Subjects were given standardized tests of cognitive function and the Clinical Dementia Rating scale (CDR). Sensory (P50, N100, P200) and cognitive (N200, P300) event-related potentials were recorded during an auditory discrimination task. Amplitudes and latencies of cortical potentials were compared among FAD mutation carriers and noncarriers.

Results: FAD mutation carriers and noncarriers did not significantly differ in age or on measures of cognitive function, but FAD carriers had a greater incidence of 0.5 CDR scores (1/10 noncarriers, 5/15 carriers). Relative to noncarriers, FAD mutation carriers had significantly longer latencies of the N100, P200, N200, and P300 components, and smaller slow wave amplitudes. Subanalyses of subjects having CDR scores of 0.0 also showed latency increases in FAD mutation carriers.

Conclusions: Auditory sensory and cognitive cortical potentials in persons with familial Alzheimer disease (FAD) mutations are abnormal approximately 10 years before dementia will be manifest. Longer event-related potential latencies suggest slowing of cortical information processing in FAD mutation carriers.

Methods: We analyzed survival in a large group of clinically diagnosed bvFTD patients (n = 91) with particular attention to demographic and clinical features at presentation. Of the 91 cases, 50 have died, with pathologic confirmation in 28.

Results: Median survival in the whole group was 9.0 years from symptom onset, and 5.4 years from diagnosis. After the exclusion of 24 "phenocopy" cases, the analysis was repeated in a subgroup of 67 patients. The mean age at symptom onset of the pathologic group was 58.5 years and 16% had a positive family history. Their median survival was 7.6 years (95% confidence interval [CI] 6.6–8.6) from symptom onset and 4.2 years (95% CI 3.4–5.0) from diagnosis. The only factor associated with shorter survival was the presence of language impairment at diagnosis.

Conclusions: Patients with definite frontotemporal dementia have a poor prognosis which is worse if language deficits are also present. This contrasts with the extremely good outcome in those with the phenocopy syndrome: of our 24 patients only 1 has died (of coincident pathology) despite, in some cases, many years of follow-up.

Methods: Patients with moderately advanced PD received bilateral intraputaminal infusion of AAV-hAADC vector. Low-dose and high-dose cohorts (5 patients in each) were studied using standardized clinical rating scales at baseline and 6 months. PET scans using the AADC tracer [¹⁸F]fluoro-l-m-tyrosine (FMT) were performed as a measure of gene expression.

Results: The gene therapy was well tolerated, but 1 symptomatic and 2 asymptomatic intracranial hemorrhages followed the operative procedure. Total and motor rating scales improved in both cohorts. Motor diaries also showed increased on-time and reduced off-time without increased "on" time dyskinesia. At 6 months, FMT PET showed a 30% increase of putaminal uptake in the low-dose cohort and a 75% increase in the high-dose cohort.

Conclusion: This study provides class IV evidence that bilateral intrastriatal infusion of adeno-associated viral type 2 vector containing the human AADC gene improves mean scores on the Unified Parkinson’s Disease Rating Scale by approximately 30% in the on and off states, but the surgical procedure may be associated with an increased risk of intracranial hemorrhage and self-limited headache.

Background: There is a need to explore nondopaminergic mechanisms of gait control as the majority of motor impairments associated with falls in PD are resistant to dopaminergic treatment. Alterations in cholinergic neurotransmission in PD may be implicated because of evidence that gait control depends on cholinergic system–mediated higher-level cortical and subcortical processing, including pedunculopontine nucleus (PPN) function.

Methods: In this cross-sectional study, 44 patients with PD (Hoehn & Yahr stages I–III) without dementia and 15 control subjects underwent a clinical assessment and [¹¹C]methyl-4-piperidinyl propionate (PMP) acetylcholinesterase (AChE) and [¹¹C]dihydrotetrabenazine (DTBZ) vesicular monoamine transporter type 2 (VMAT2) brain PET imaging.

Results: Seventeen patients (38.6%) reported a history of falls and 27 patients had no falls. Analysis of covariance of the cortical AChE hydrolysis rates demonstrated reduced cortical AChE in the PD fallers group (–12.3%) followed by the PD nonfallers (–6.6%) compared to control subjects (F = 7.22, p = 0.0004). Thalamic AChE activity was lower only in the PD fallers group (–11.8%; F = 4.36, p = 0.008). There was no significant difference in nigrostriatal dopaminergic activity between PD fallers and nonfallers.

Conclusions: Unlike nigrostriatal dopaminergic denervation, cholinergic hypofunction is associated with fall status in Parkinson disease (PD). Thalamic AChE activity in part represents cholinergic output of the pedunculopontine nucleus (PPN), a key node for gait control. Our results are consistent with other data indicating that PPN degeneration is a major factor leading to impaired postural control and gait dysfunction in PD.

Methods: In this Institutional Review Board–approved study, we retrospectively analyzed the records of 8 adult patients treated for recurrent ependymoma and anaplastic ependymoma with bevacizumab containing chemotherapy regimens. We determined radiographic response (Macdonald criteria), median time to progression (TTP), and median overall survival (OS; Kaplan-Meier method).

Results: There were 4 men and 4 women with a median age of 40 years (range, 20–65). Prior treatment included surgery (n = 8), RT (8), temozolomide (5), and carboplatin (4). Bevacizumab (5–15 mg/kg every 2–3 weeks) was administered alone (2) or concurrently with cytotoxic chemotherapy including irinotecan (3), carboplatin (2), or temozolomide (1). Six patients achieved a partial response (75%) and 1 remained stable for over 8 months. Median TTP was 6.4 months (95% confidence interval 1.4–7.4) and median OS was 9.4 months (95% confidence interval 7.0–not reached), with a median follow-up of 5.2 months among 5 surviving patients (63%).

Conclusions: The radiographic response rate to bevacizumab-containing regimens is high. A prospective study is warranted.

Methods: The study population included 658 patients with ALS consecutively observed in 2 Italian ALS centers between 2000 and 2006. They were compared to a series of 658 healthy subjects, matched by age and gender.

Results: The mean levels of total cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and the LDL/HDL ratio were similar in patients with ALS and controls. Total cholesterol, HDL, triglyceride, and LDL/HDL ratio levels showed a significant decrease in patients with forced vital capacity <70% compared to those with FVC ≥90%. For each level of ALS-FRS, poorer respiratory function was related to a lower LDL/HDL ratio. Univariate survival analysis did not find any significant effect of LDL/HDL ratio on survival, either when comparing patients with ratios ≤2.99 vs >2.99 or patients in the first quartile of LDL/HDL ratio (≤1.67) vs those in the fourth quartile (>2.79). No dose-response was found for LDL/HDL ratio subdividing patients into 5 quintiles.

Conclusion: Our findings do not support the observation that patients with amyotrophic lateral sclerosis have hyperlipidemia or that hyperlipidemia in this population is related to longer survival. However, some evidence emerged that respiratory impairment, but not a worse clinical status or a lower body mass index, is related to a decrease in blood lipids and LDL/HDL ratio.

Methods: We reviewed the medical records of patients with PMA (n = 91) or ALS (n = 871) from our ALS Center and verified survival by telephoning the families or using the National Death Index.

Results: In PMA, patients were more likely to be male (p < 0.001), older (p = 0.007), and lived longer (p = 0.01) than in ALS. Cox model analysis suggested that the risk of death increased with age at onset in both patient groups (p < 0.005). Upper motor neuron (UMN) signs developed in 22% of patients with PMA within 61 months after diagnosis. Demographic and other clinical variables did not differ at diagnosis between those who did or did not develop UMN signs. In PMA, the factors present at diagnosis that predicted shorter survival were greater number of body regions affected, lower forced vital capacity, and lower ALS Functional Rating Scale–Revised score. Noninvasive ventilation and gastrostomy were used frequently in PMA.

Conclusion: Although patients with progressive muscular atrophy (PMA) tended to live longer than those with amyotrophic lateral sclerosis (ALS), shorter survival in PMA is associated with the same risk factors that predict poor survival in ALS. Additionally, PMA is relentlessly progressive, and UMN involvement can occur, as also reported in imaging and postmortem studies. For these reasons, PMA should be considered a form of ALS.

Methods: A Medline literature search was conducted for the period between 2003 and April 2009 using the search terms smoking and (ALS or "amyotrophic lateral sclerosis" or MND or "motor neuron disease"). The references of primary articles and reviews were checked to assure completeness of the search. Primary articles published since the previous review were classified as before.

Results: Twenty-eight titles were identified, but only 7 articles met inclusion criteria. Of these, 1 provided class II evidence, and 1 class III evidence: both showed increased risk of ALS with smoking. The class II study showed a dose-response effect, and risk decreasing with number of years since quitting smoking. Five articles provided class IV or V evidence, which may not be relied upon to draw conclusions.

Conclusions: Smoking may be considered an established risk factor for sporadic amyotrophic lateral sclerosis (ALS) (level A rating; 3 class II studies, 1 class III study). Evidence-based analysis of epidemiologic data shows concordance among results of better-designed studies linking smoking to ALS, and lets those results drive the conclusions.

Methods: We performed extensive characterization by array-based copy number assessment (aCGH), HIPK2 copy number analysis, and BRAF rearrangement and mutation analysis in a set of 79 PAs, including 9 tumors from patients with neurofibromatosis type 1 (NF1).

Results: We identified 1 of 3 previously identified BRAF rearrangements in 42/70 sporadic PAs. An additional 2 tumors with no rearrangement also exhibited BRAF mutation, including a novel 3-base insertion. As predicted from the genomic organization at this locus, 22/36 tumors with BRAF rearrangement also exhibited corresponding HIPK2 amplification. However, 14/36 tumors with BRAF rearrangement had no detectable HIPK2 gene amplification and 6/20 tumors demonstrated HIPK2 amplification without apparent BRAF rearrangement or mutation. Only 12/70 PAs lacked detectable BRAF or HIPK2 alterations. Importantly, none of the 9 PA tumors from NF1 patients exhibited BRAF rearrangement or mutation.

Conclusions: BRAF rearrangement represents the most common genetic alteration in sporadic, but not neurofibromatosis type 1-associated, pilocytic astrocytomas (PAs). These findings implicate BRAF in the pathogenesis of these common low-grade astrocytomas in children, and suggest that PAs arise either from NF1 inactivation or BRAF gain of function.

Methods: A case-control study of handwriting samples from children with and without autism spectrum disorders (ASD) was performed using the Minnesota Handwriting Assessment. Samples were scored on an individual letter basis in 5 categories: legibility, form, alignment, size, and spacing. Subjects were also tested on the Wechsler Intelligence Scale for Children–IV and the Physical and Neurological Examination for Subtle (Motor) Signs.

Results: We found that children with ASD do indeed show overall worse performance on a handwriting task than do age- and intelligence-matched controls. More specifically, children with ASD show worse quality of forming letters but do not show differences in their ability to correctly size, align, and space their letters. Within the ASD group, motor skills were significantly predictive of handwriting performance, whereas age, gender, IQ, and visuospatial abilities were not.

Conclusions: We addressed how different elements of handwriting contribute to impairments observed in children with autism. Our results suggest that training targeting letter formation, in combination with general training of fine motor control, may be the best direction for improving handwriting performance in children with autism.

Methods: The placebo arms of 2 clinical trials were analyzed. One cohort consisted of 548 patients with relapsing-remitting (RR) MS enrolled in a 14-month, randomized, double-blind, placebo-controlled trial of oral glatiramer acetate. The second cohort consisted of 358 patients with secondary progressive (SP) MS still experiencing relapses enrolled in a 3-year, randomized, double-blind, placebo-controlled trial of interferon beta-1b.

Results: At baseline, T2LV was associated with disease duration (p < 0.001), age at MS onset (p < 0.001), and disability (p < 0.001). The relationship between baseline T2LV and Expanded Disability Status Scale (EDSS) was not significantly different between patients with RRMS and SPMS. At a multivariate analysis, T2LV change was associated with the number of on-trial relapses (p < 0.001) and age at MS onset (p = 0.02). The correlations of T2LV change with baseline EDSS and EDSS changes were not significant.

Conclusions: We showed that the plateauing relationship between T2 lesion volume and disability in multiple sclerosis is not always present and is likely due to the reduced frequency of "inflammatory" events in the most common form of secondary progressive multiple sclerosis.

Methods: Women in the Nurses’ Health Study (n = 121,700) and Nurses’ Health Study II (n = 116,671) provided information on weight at age 18 and weight and height at baseline, from which body mass index was derived. Women also selected silhouettes representing their body size at ages 5, 10, and 20. Over the total 40 years of follow-up in both cohorts combined, we confirmed 593 cases of MS. Cox proportional hazards models, adjusting for age, latitude of residence, ethnicity, and cigarette smoking, were used to estimate the rate ratios and 95% confidence intervals (CI).

Results: Obesity at age 18 (body mass index ≥30 kg/m²) was associated with a greater than twofold increased risk of MS (multivariate relative risk_pooled = 2.25, 95% CI: 1.50-3.37, p trend <0.001). After adjusting for body size at age 20, having a large body size at ages 5 or 10 was not associated with risk of MS, whereas a large body size at age 20 was associated with a 96% increased risk of MS (95% CI: 1.33-2.89, p trend = 0.009). No significant association was found between adult body mass and MS risk.

Conclusions: Obese adolescents have an increased risk of developing multiple sclerosis (MS). Although the mechanisms of this association remain uncertain, this result suggests that prevention of adolescent obesity may contribute to reduced MS risk.

25(OH)D = 25-hydroxyvitamin D; BMI = body mass index; CI = confidence interval; MS = multiple sclerosis; NHS = Nurses’ Health Study; NHSII = Nurses’ Health Study II; RR = relative risk.

Methods: We recorded the clinical outcome of 60 patients with PML (73% HIV+) who were prospectively evaluated between 2000 and 2007 for the presence of JC virus (JCV)-specific CD8+ cytotoxic T-lymphocytes (CTL) in blood.

Results: Estimated probability of survival at 1 year was 52% for HIV+/PML and 58% for HIV– patients with PML. Patients with PML with detectable CTL within 3 months of diagnosis had a 1-year estimated survival of 73% compared to 46% for those without CTL (hazard ratio [HR] for death = 0.47, 95% confidence interval [CI] 0.13-1.75, p = 0.26). Patients with CTL response had an increased likelihood of having contrast enhancement of PML lesions and immune reconstitution inflammatory syndrome (odds ratio 3.7 and 7.8). Estimated 1-year survival was 48% in HIV+ patients with PML with CD4 count <200/µL at PML diagnosis compared to 67% in those with CD4 >200/µL (HR for death 1.41, 95% CI 0.27-7.38, p = 0.68). JCV DNA was detected in the urine of 48% and in the blood of 56% of patients with PML, but viruria and viremia were not associated with survival.

Conclusions: The presence of JC virus (JCV)-specific cytotoxic T-lymphocytes (CTL) was associated with a trend toward longer survival in patients with progressive multifocal leukoencephalopathy (PML), which was more pronounced than the impact of CD4 count in HIV+ patients with PML early after diagnosis. Despite the association of contrast enhancement and immune reconstitution inflammatory syndrome with JCV-specific CTL, these cannot be considered as surrogate markers for the prognostic value of the CTL. Strategies aiming at improving the cellular immune response may improve the course of PML.

CE = contrast enhancement; CI = confidence interval; CTL = cytotoxic T-lymphocytes; HR = hazard ratio; IQR = interquartile range; IRIS = immune reconstitution inflammatory syndrome; JCV = JC virus; PBMC = peripheral blood mononuclear cells; PML = progressive multifocal leukoencephalopathy.

Methods: Thirty-two years of longitudinal body weight, BMI, waist circumference, and waist-to-hip ratio (WHR) data, from the Prospective Population Study of Women in Sweden, were related to dementia. A representative sample of 1,462 nondemented women was followed from 1968 at ages 38-60 years, and subsequently in 1974, 1980, 1992, and 2000, using neuropsychiatric, anthropometric, clinical, and other measurements. Cox proportional hazards regression models estimated incident dementia risk by baseline factors. Logistic regression models including measures at each examination were related to dementia among surviving participants 32 years later.

Results: While Cox models showed no association between baseline anthropometric factors and dementia risk, logistic models showed that a midlife WHR greater than 0.80 increased risk for dementia approximately twofold (odds ratio 2.22, 95% confidence interval 1.00-4.94, p = 0.049) among surviving participants. Evidence for reverse causality was observed for body weight, BMI, and waist circumference in years preceding dementia diagnosis.

Conclusions: Among survivors to age 70, high midlife waist-to-hip ratio may increase odds of dementia. Traditional Cox models do not evidence this relationship. Changing anthropometric parameters in years preceding dementia onset indicate the dynamic nature of this seemingly simple relationship. There are midlife and late-life implications for dementia prevention, and analytical considerations related to identifying risk factors for dementia.

ADCVD = AD with cerebrovascular disease; BMI = body mass index; DBP = diastolic blood pressure; DSM-III-R = Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised; HAAS = Honolulu Asia Aging Study; PPSW = Prospective Population Study of Women; SBP = systolic blood pressure; SES = socioeconomic status; VaD = vascular dementia; WHR = waist-to-hip ratio.

Methods: A subset of 20 nondemented older adults was drawn from the Einstein Aging Study, a community-based sample from the Bronx, NY. Pain was measured on 3 time scales: 1) acute pain right now (pain severity); 2) pain over the past 4 weeks (Short Form–36 Bodily Pain); 3) chronic pain over the past 3 months (Total Pain Index). Hippocampal data included volume data normalized to midsagittal area and N-acetylaspartate to creatine ratios (NAA/Cr).

Results: Smaller hippocampal volume was associated with higher ratings on the Short Form–36 Bodily Pain (r_s = 0.52, p = 0.02) and a nonsignificant trend was noted for higher ratings of acute pain severity (r_s = –0.44, p = 0.06). Lower levels of hippocampal NAA/Cr were associated with higher acute pain severity (r_s = –0.45, p = 0.05). Individuals with chronic pain had a nonsignificant trend for smaller hippocampal volumes (t = 2.00, p = 0.06) and lower levels of hippocampal NAA/Cr (t = 1.71, p = 0.10).

Conclusions: Older adults who report more severe acute or chronic pain have smaller hippocampal volumes and lower levels of hippocampal N-acetylaspartate/creatine, a marker of neuronal integrity. Future studies should consider the role of the hippocampus and other brain structures in the development and experience of pain in healthy elderly and individuals with Alzheimer disease.

Methods: Voxel-based morphometry (VBM) was used to assess atrophy in 14 PCA, 10 LPA, and 16 EO-AD patients compared to 65 healthy controls. Genetic analysis for APOE was conducted in 30 patients and 44 controls. Four patients came to autopsy. An additional 14 were studied with the beta-amyloid specific PET with tracer ¹¹C-labeled Pittsburgh Compound-B (PIB).

Results: VBM results demonstrated that, compared to controls, each patient group showed a large area of overlapping atrophy in bilateral parietal, occipital, precuneus, posterior cingulate, posterior temporal, and hippocampal regions. Surrounding this common area, group-specific atrophy was found in small, symptom-specific regions for each group: the right ventral-occipital and superior parietal regions in PCA, the left middle and superior temporal gyri in LPA, and the prefrontal cortex in EO-AD. APOE 4 frequency was higher in all patient groups compared to controls. Four PCA, 5 LPA, and 8 EO-AD patients showed evidence of cortical amyloid at pathology (n = 3) or on PIB-PET (n = 14).

Conclusions: Logopenic progressive aphasia and posterior cortical atrophy showed largely overlapping anatomic and biologic features with early age at onset of Alzheimer disease, suggesting that these clinical syndromes represent the spectrum of clinical manifestation of the nontypical form of Alzheimer disease that presents at an early age.

AD = Alzheimer disease; CBD = corticobasal degeneration; EO-AD = early age at onset of Alzheimer disease; LPA = logopenic progressive aphasia; MAC = Memory and Aging Center; PCA = posterior cortical atrophy; PIB = Pittsburgh Compound-B; PPA = primary progressive aphasia; UCSF = University of California San Francisco; VBM = voxel-based morphometry.

Methods: Forty-eight individuals (75% of the contacted sample) agreed to participate in the current study and were instructed to complete electronic interviews using a personal digital assistant 5 times per day over a 1-week period.

Results: More than 80% of programmed assessments were completed by the sample, and no evidence was found for fatigue effects. Expected patterns of associations were observed among daily life variables, and data collected through ambulatory monitoring were significantly correlated with standard clinic-based measures of similar constructs.

Conclusion: Support was found for the feasibility and validity of computerized ambulatory monitoring with stroke patients. The application of these novel methods with stroke patients should provide complementary information that is inaccessible to standard hospital-based assessments and permit increased understanding of the significance of clinical results and test scores for daily life experience.

DSM-IV-R = Diagnostic and Statistical Manual of Mental Disorders, 4th edition, revised; EMA = ecologic momentary assessment; ESM = experience sampling method; HAM-A = Hamilton Anxiety Rating Scale; HAM-D = Hamilton Depression Rating Scale; MMSE = Mini-Mental State Examination; PDA = personal digital assistant; SE = standard error.

Methods: Data were collected in 12 centers across 10 countries in America, Asia, and Europe. In addition to the NMSS, the following measures were applied: Scales for Outcomes in Parkinson’s Disease (SCOPA)-Motor, SCOPA-Psychiatric Complications (SCOPA-PC), SCOPA-Cognition, Hoehn and Yahr Staging (HY), Clinical Impression of Severity Index for Parkinson’s Disease (CISI-PD), SCOPA-Autonomic, Parkinson’s Disease Sleep Scale (PDSS), Parkinson’s Disease Questionnaire–39 items (PDQ-39), and EuroQol–5 dimensions (EQ-5D). NMSS acceptability, reliability, validity, and precision were analyzed.

Results: Four hundred eleven patients with PD, 61.3% men, were recruited. The mean age was 64.5 ± 9.9 years, and mean disease duration was 8.1 ± 5.7 years. The NMSS score was 57.1 ± 44.0 points. The scale was free of floor or ceiling effects. For domains, the Cronbach coefficient ranged from 0.44 to 0.85. The intraclass correlation coefficient (0.90 for the total score, 0.67–0.91 for domains) and Lin concordance coefficient (0.88) suggested satisfactory reproducibility. The NMSS total score correlated significantly with SCOPA-Autonomic, PDQ-39, and EQ-5D (r_S = 0.57–0.70). Association was close between NMSS domains and the corresponding SCOPA–Autonomic domains (r_S = 0.51–0.65) and also with scales measuring related constructs (PDSS, SCOPA-PC) (all p < 0.0001). The NMSS total score was higher for women (p < 0.02) and for increasing disease duration, HY, and CISI-PD severity level (p < 0.001). The SEM was 13.91 for total score and 1.71 to 4.73 for domains.

Conclusion: The Non-Motor Symptoms Scale is an acceptable, reproducible, valid, and precise assessment instrument for nonmotor symptoms in Parkinson disease.

Methods: A cohort of 241 normal elderly volunteers was followed for up to 20 years with regular assessments of cognitive abilities using the Cambridge Cognitive Examination (CAMCOG); 91 participants developed MCI. We used interval-censored survival analysis statistical methods to model which baseline cognitive tests best predicted the time to convert to MCI.

Results: Out of several baseline variables, only age and CAMCOG subscores for expression and learning/memory were predictors of the time to conversion. The time to conversion was 14% shorter for each 5 years of age, 17% shorter for each point lower in the expression score, and 15% shorter for each point lower in the learning score. We present in tabular form the probability of converting to MCI over intervals between 2 and 10 years for different combinations of expression and learning scores.

Conclusion: In apparently normal elderly people, subtle measurable cognitive deficits that occur within the normal range on standard testing protocols reliably predict the time to clinically relevant cognitive impairment long before clinical symptoms are reported.

Methods: In this case-control study, 101 subjects with FTD were identified. Atlas-based parcellation generated temporal, frontal, and parietal grey matter volumes which were used to identify subjects with a right temporal dominant atrophy pattern. Clinical, neuropsychological, genetic, and neuropathologic features were reviewed. The subjects with right temporal FTD were grouped by initial clinical diagnosis and voxel-based morphometry was used to assess grey matter loss in the different groups, compared to controls, and each other.

Results: We identified 20 subjects with right temporal FTD. Twelve had been initially diagnosed with behavioral variant FTD (bvFTD), and the other 8 with semantic dementia (SMD). Personality change and inappropriate behaviors were more frequent in the bvFTD group, while prosopagnosia, word-finding difficulties, comprehension problems, and topographagnosia were more frequent in the SMD group. The bvFTD group showed greater loss in frontal lobes than the SMD group. The SMD group showed greater fusiform loss than the bvFTD group. All 8 bvFTD subjects with pathologic/genetic diagnosis showed abnormalities in tau protein (7 with tau mutations), while all three SMD subjects with pathology showed abnormalities in TDP-43 (p = 0.006).

Conclusions: We have identified 2 subtypes of right temporal variant frontotemporal dementia (FTD) allowing further differentiation of FTD subjects with underlying tau pathology from those with TDP-43 pathology.

Methods: We collected blood samples from a cohort of 225 patients with a diagnosis within the FTLD spectrum and examined the heritability of FTLD by giving each patient a family history score, from 1 (a clear autosomal dominant history of FTLD) through to 4 (no family history of dementia). We also looked for mutations in each of the 5 disease-causing genes (MAPT, GRN, VCP, CHMP2B, and TARDP) and the FUS gene, known to cause motor neuron disease.

Results: A total of 41.8% of patients had some family history (score of 1, 2, 3, or 3.5), although only 10.2% had a clear autosomal dominant history (score of 1). Heritability varied across the different clinical subtypes of FTLD with the behavioral variant being the most heritable and frontotemporal dementia–motor neuron disease and the language syndromes (particularly semantic dementia) the least heritable. Mutations were found in MAPT (8.9% of the cohort) and GRN (8.4%) but not in any of the other genes. Of the remaining patients without mutations but with a strong family history, 7 had pathologic confirmation, falling into 2 groups: type 3 FTLD-TDP without GRN mutations (6) and FTLD-UPS (1).

Conclusion: These findings show that frontotemporal lobar degeneration (FTLD) is a highly heritable disorder but heritability varies between the different syndromes. Furthermore, while MAPT and GRN mutations account for a substantial proportion of familial cases, there are other genes yet to be discovered, particularly in patients with type 3 FTLD-TDP without a GRN mutation.

Methods: Between July 2006 and April 2008, this multicenter prospective cohort study included adult comatose patients admitted after CPR and treated with induced mild hypothermia (32–34°C). SSEP was performed during hypothermia, and in patients who remained comatose after rewarming, a second SSEP was performed. Neurologic outcome was assessed 30 days after admission with the Glasgow Outcome Scale.

Results: Seventy-seven consecutive patients were included in 2 hospitals. In 13 patients (17%), the cortical N20 response during hypothermia was bilaterally absent. In 9 of these 13 patients in whom SSEP could be repeated during normothermia, the N20 response was also absent, yielding a positive predictive value of 1.00 (95% confidence interval [CI] 0.70–1.00). All 13 patients with absent SSEP during hypothermia had a poor neurologic outcome, yielding a positive predictive value of 1.00 (95% CI 0.77–1.00).

Conclusions: The results of this pilot study show that bilaterally absent cortical N20 responses of median nerve somatosensory evoked potentials performed during mild hypothermia after resuscitation can predict a poor neurologic outcome. We started a larger multicenter prospective cohort study to confirm these results.

Methods: A population based case-control study was conducted in Denmark of 13,695 patients with a primary diagnosis of PD recorded in the Danish National Hospital Register during the period 1986–2006. Each case was matched on year of birth and sex to 5 population controls selected at random from among inhabitants of Denmark who were alive at the date of the patient's diagnosis. The main exposure measure was a hospital diagnosis of 1 of 32 selected autoimmune diseases recorded 5 or more years before the index date in the files of the Danish Hospital Register.

Results: We observed no overall association between a diagnosis of autoimmune disease and risk for subsequent PD (odds ratio 0.96, 95% confidence interval 0.85–1.08). In a subgroup of patients with autoimmune diseases with systemic involvement, primarily rheumatoid arthritis, we saw a decrease in risk for PD of 30%.

Conclusions: Our results do not support the hypothesis that autoimmune diseases increase the risk for Parkinson disease. The decreased risk observed among patients with rheumatoid arthritis might be explained by underdiagnosis of movement disorders such as Parkinson disease in this patient group or by a protective effect of the treatment with anti-inflammatory drugs over prolonged periods.

Methods: The Mini-Mental State Examination (MMSE) was administered periodically over a median follow-up period of 6.5 years to participants in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism trial and its extension studies. Cognitive impairment was defined as scoring 2 standard deviations below age- and education-adjusted MMSE norms.

Results: Cumulative incidence of cognitive impairment in the 740 participants with clinically confirmed PD (baseline age 61.0 ± 9.6 years, Hoehn-Yahr stage 1–2.5) was 2.4% (95% confidence interval: 1.2%–3.5%) at 2 years and 5.8% (3.7%–7.7%) at 5 years. Subjects who developed cognitive impairment (n = 46) showed significant progressive decline on neuropsychological tests measuring verbal learning and memory, visuospatial working memory, visuomotor speed, and attention, while the performance of the nonimpaired subjects (n = 694) stayed stable. Cognitive impairment was associated with older age, hallucinations, male gender, increased symmetry of parkinsonism, increased severity of motor impairment (except for tremor), speech and swallowing impairments, dexterity loss, and presence of gastroenterologic/urologic disorders at baseline.

Conclusions: The relatively low incidence of cognitive impairment in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism study may reflect recruitment bias inherent to clinical trial volunteers (e.g., younger age) or limitations of the Mini-Mental State Examination–based criterion. Besides confirming known risk factors for cognitive impairment, we identified potentially novel predictors such as bulbar dysfunction and gastroenterologic/urologic disorders (suggestive of autonomic dysfunction) early in the course of the disease.

Methods: The present study was a 2-arm, 12-week, randomized controlled trial including a poststudy follow-up period of 12 weeks. Thirty-eight moderately impaired patients with MS were randomized to a PRT exercise group (n = 19) or a control group (n = 19). The exercise group completed a biweekly 12-week lower extremity PRT program and was afterward encouraged to continue training. After the trial, the control group completed the PRT intervention. Both groups were tested before and after 12 weeks of the trial and at 24 weeks (follow-up), where isometric muscle strength of the knee extensors (KE MVC) and functional capacity (FS; combined score of 4 tests) were evaluated.

Results: KE MVC and FS improved after 12 weeks of PRT in the exercise group (KE MVC: 15.7% [95% confidence interval 4.3–27.0], FS: 21.5% [95% confidence interval 17.0–26.1]; p < 0.05), and the improvements were better than in the control group (p < 0.05). The improvements of KE and FS in the exercise group persisted at follow-up after 24 weeks. Also, the exercise effects were reproduced in the control group during the 12-week posttrial PRT period.

Conclusions: Twelve weeks of intense progressive resistance training of the lower extremities leads to improvements of muscle strength and functional capacity in patients with multiple sclerosis, the effects persisting after 12 weeks of self-guided physical activity.

Level of evidence: The present study provides level III evidence supporting the hypothesis that lower extremity progressive resistance training can improve muscle strength and functional capacity in patients with multiple sclerosis.

Methods: Because a robust effect of IFNβ is a decrease in enhancing lesions on brain MRI scans, the Betaseron Copaxone in Multiple Sclerosis With Triple-Dose Gadolinium and 3-Tesla MRI Endpoints (BECOME) study, a head-to-head study of IFNβ-1b vs glatiramer acetate with a primary endpoint of enhancing lesions on MRI, provided an excellent opportunity to determine the effect of NAbs on MRI activity. We measured NAbs and IFNβ bioactivity by myxovirus resistance protein A gene expression and identified 2 groups of patients: one labeled "bioactivity preserved," with absent NAbs and robust IFNβ bioactivity (n = 8), and the other labeled "bioactivity lost," with high levels of NAbs and diminished bioactivity (n = 7). The development of enhancing lesions in the groups was then compared.

Results: The incidence of NAbs and effect of NAbs on bioactivity were consistent with previous studies. We analyzed MRI outcomes in patients with NAbs at levels high enough to abolish bioactivity relative to patients without NAbs. For the preserved bioactivity group, the enhancing lesion/scan ratio decreased from 7.6 in the pretreatment period to 2.6 in the posttreatment period, a 66% decrease. For the lost bioactivity group, the decrease was 8.5 to 5.8, only a 32% decrease. Thus, lost bioactivity from high levels of NAbs resulted in reduced therapeutic efficacy of IFNβ as manifested by diminished reductions in enhancing lesions on MRI.

Conclusions: High levels of anti–interferon beta (IFNβ) antibodies, which result in diminished bioactivity, are correlated with reduced therapeutic efficacy of IFNβ.

Methods: In this multicenter, open-label study, antibody status was measured at screening, and then antibody status, levels of MxA, viperin, and IFIT-1 were measured at baseline (≤8 weeks after screening) and 6 months after baseline in patients with relapsing forms of MS treated with IM IFNβ-1a, subcutaneous (SC) IFNβ-1a, or IFNβ-1b.

Results: Treatment with IM IFNβ-1a was associated with a lower rate of NAb formation among 718 patients screened (p < 0.0001 vs SC IFNβ-1a 22 µg, 44 µg, and IFNβ-1b). At baseline, patients who were binding antibody positive (BAb+)/neutralizing antibody positive (NAb+) had lower MxA, viperin, and IFIT-1 response compared with BAb-negative (BAb–)/NAb-negative (NAb–) patients (all p < 0.0001). Analyses stratified by NAb titer level among BAb+/NAb+ patients showed diminished biomarker response in patients with NAb titers from 20 to 99 tenfold reduction units (TRU) and abolished response in patients with NAb titers ≥100 TRU compared with BAb–/NAb– patients. A majority of patients BAb+/NAb+ at screening remained BAb+/NAb+ throughout the study, and biomarker responses remained consistently depressed in these patients at month 6.

Conclusions: These data provide evidence that high titers of neutralizing antibodies abolish the in vivo response to interferon beta.

Methods: Sudomotor function was analyzed in a cohort of 21 patients with ganglionic 3 nicotinic acetylcholine receptor (nAChR) antibody positive autoimmune autonomic ganglionopathy. Standard measurements of sudomotor function were used including the Thermoregulatory Sweat Test and Quantitative Sudomotor Axon Reflex Test.

Results: The clinical presentation in all patients was characterized by widespread sudomotor dysfunction. Sudomotor impairment was predominantly postganglionic in 17 of the 21 patients studied. Higher ganglionic 3 nAChR antibody levels resulted in progressive postganglionic predominant dysfunction (postganglionic, r = 0.637, p = 0.002; mixed ganglionic, r = 0.709, p < 0.001). The pattern of anhidrosis on Thermoregulatory Sweat Testing was consistent with a ganglionopathy in the majority of patients (14 of 21) and a distal pattern in a minority of patients (8 of 21). These patterns of anhidrosis coupled with increasing postganglionic dysfunction in a proximal to distal pattern (foot > distal leg > proximal leg > forearm) indicate lesions at both the ganglia and distal axon of the postganglionic sudomotor sympathetic neuron.

Conclusions: Our data characterize the unique sudomotor dysfunction in autoimmune autonomic ganglionopathy as widespread, predominantly postganglionic, and a result of lesions at both the ganglia and distal axon. This study provides important support to the hypothesis that this disorder represents a ganglionic neuropathy.

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.

Methods: A total of 151 patients with AD of whom we had baseline CSF were included from our memory clinic. All patients had at least 2 Mini-Mental State Examination (MMSE) scores, obtained no less than 1 year apart. Linear mixed models were used to assess associations between CSF biomarkers and the rate of cognitive decline as measured with the MMSE. CSF biomarkers were used in quintiles, random intercept and random slope with time were assumed, and the analyses were corrected for sex and age.

Results: The patients with AD (45% women, age 66 ± 9 years, baseline MMSE 22 ± 4) had a follow-up period of 2.0 (1.0–5.0) years. Linear mixed models revealed no relations between any CSF biomarker and baseline MMSE. However, CSF biomarkers did predict cognitive decline over time. A low p-tau-181/tau ratio was the strongest predictor with a dose-dependent effect (lowest vs highest quintile: 2.9 vs 1.3 MMSE points annual decline, p for trend <0.001). In addition, low Aβ₄₂, high tau, and high tau/Aβ₄₂-ratio were associated with rapid cognitive decline (p < 0.05).

Conclusion: At the time of diagnosis, a combination of high CSF tau without proportionally elevated p-tau-181 is associated with a faster rate of cognitive decline.

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.

Methods: We studied 21 patients with a single pathogenic splicing mutation in the PGRN gene (c.709-1G>A) in the same tertiary referral center using homogenous diagnostic criteria and protocols. All patients were of Basque descent.

Results: Patients exhibited a variable phenotype both in age at onset and initial symptoms. Behavioral variant frontotemporal dementia (52.4%) and progressive nonfluent aphasia (23.8%) were the most common presenting syndromes. Apathy was the most common behavioral symptom. Patients developed a relatively rapidly progressive dementia with features that led to a secondary diagnosis in 61.9% of cases 2 years after primary diagnosis. Notably, this secondary or tertiary diagnosis was corticobasal syndrome in 47.6% of cases, which confirmed the neuropsychological features of parietal lobe dysfunction seen at the initial assessment in 81.8% of patients.

Conclusions: Patients carrying the c.709-1G>A mutation in the PGRN gene showed heterogeneous clinical and neuropsychological features and commonly developed corticobasal syndrome as the disease progressed.

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.

Methods: We used the medical records–linkage system of the Rochester Epidemiology Project to identify 196 subjects who developed PD in Olmsted County, Minnesota, from 1976 through 1995. Each incident case was matched by age (±1 year) and sex to a general population control. We reviewed the complete medical records of cases and controls in the system to detect anemia defined using the World Health Organization criteria.

Results: Anemia was more common in the history of cases than of controls (odds ratio 2.00, 95% confidence interval 1.31–3.06, p = 0.001). The association remained significant after adjustment for cigarette smoking, exposure to pesticides, or hysterectomy (in women). The association was not significantly different between men and women, or between PD patients with or without rest tremor. Analyses stratified by time of onset of anemia showed a greater association for anemia that started 20 to 29 years before the onset of PD. Hemoglobin levels were slightly but consistently lower in cases than in controls across all ages.

Conclusions: Our results support an association between anemia experienced early in life and the later development of Parkinson disease. The interpretation of this association remains uncertain.

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.

Objective: Using the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry, we investigated the frequency of osteoporosis, fractures, and clinical risk factors for fracture in MS.

Methods: In 2007, 9,346 NARCOMS participants reported fractures and clinical risk factors for fractures including history of osteoporosis or osteopenia (low bone mass), sedentary level of physical activity, falls in the last year, current smoking status, family history of osteoporosis, and impaired mobility.

Results: Among responders, 2,501 (27.2%) reported low bone mass. More than 15% of responders reported a history of fracture after age 13 years (n = 1,482). Among those reporting fractures, 685 (46.2%) reported multiple fractures, while 522 (35.2%) reported a wrist fracture, 165 (11.1%) reported a vertebral fracture, and 100 (7.4%) reported a hip fracture. Excluding age, 1,413 (15.1%) participants had 1 clinical risk factor for fracture, 2,341 (25.0%) had 2, and 5,393 (57.7%) had 3 or more. Among participants with a history of fracture, 746 (55%) reported taking calcium supplements, 858 (68.8%) reported taking vitamin D supplements or a multivitamin with vitamin D, and 334 (22.5%) reported taking a bisphosphonate.

Conclusion: Patients with multiple sclerosis (MS) often have multiple risk factors for osteoporotic fractures. Many patients with MS with low bone mass or previous fractures are not taking supplemental calcium or vitamin D, suggesting a potential area of improvement in care.

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-Barré 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.