Serotonin, a neurotransmitter synthesized from tryptophan, has been proposed to play a key role in central fatigue. In this study, we examined whether tryptophan itself and/or its two metabolites, kynurenic acid (KYNA) and quinolinic acid (QUIN), are involved in central fatigue.

Experiments were conducted using Sprague-Dawley rats (SDR) and Nagase analbuminemic rats (NAR). Central fatigue was assessed by treadmill running and a Morris water maze test. Microdialysis was used to collect samples for measurement of extracellular concentration of tryptophan, serotonin and 5-hydroxyindoleacetic acid (5-HIAA) and to infuse test agents. To examine the kinetics of release, synaptosomes in the striatum were prepared in vitro to measure intra- and extrasynaptosomal concentration of tryptophan, serotonin and 5-HIAA.

The concentration of tryptophan secreted into the extracellular space of the striatum was higher during fatigue only, and quickly returned to basal levels with recovery from fatigue. Running time to exhaustion was reduced by activation of tryptophan receptors. Time to exhaustion was shorter in NAR, which maintain a higher extracellular level of striatum tryptophan than SDR. Impaired memory performance in a water maze task after tryptophan treatment was attributable to high levels of KYNA and QUIN in the hippocampus acting synergistically on N-methyl-D-aspartic acid receptors. When branched-chain amino acids were administered, tryptophan transport to the extracellular space of the striatum was drastically inhibited.

Our findings demonstrate that the increase in fatigue which occurs because of excessively elevated brain tryptophan can be further amplified by the use of synthetic KYNA and QUIN.

The primary aim of the present study was to determine the survival rates and identify predictors of disease duration in a cohort of Huntington's disease (HD) patients from Southern Italy.

All medical records of HD patients followed between 1977 and 2008 at the Department of Neurological Sciences of Federico II University in Naples were retrospectively reviewed and 135 patients were enrolled in the analysis. At the time of data collection, 41 patients were deceased (19 males and 22 females) with a mean ± SD age at death of 56.6 ± 14.9 years (range 18-83).

The median survival time was 20 years (95% CI: 18.3-21.7). Cox regression analysis showed that the number of CAG in the expanded allele (HR 1.09 for 1 point triplet increase, p=0.002) and age of onset (HR 1.05 for 1 point year increase, p=0.022) were independent and significant predictors of lower survival rates.

We believe that these findings are important for a better understanding of the natural history of the disease and may be relevant in designing future therapeutic trials.

Abnormal somatosensory processing may contribute to motor impairments observed in Parkinson's disease (PD). Dopaminergic medications have been shown to alter somatosensory processing such that tactile perception is improved. In PD, it remains unclear whether the temporal sequencing of tactile stimuli is altered and if dopaminergic medications alter this perception.

Somatosensory tactile perception was investigated using temporal order judgment in patients with Parkinson's disease on and off dopaminergic medications and in aged-matched healthy controls. Measures of temporal order judgment were acquired using computer controlled stimulation to digits 2 and 3 on the right hand and subjects were required to determine which stimuli occurred first. Two experimental tasks were compared, temporal order judgment without and with synchronization whereby digits 2 and 3 were vibrated synchronously in advance of the temporal order judgment sequence of stimuli.

Temporal order judgment in PD patients off and on medications were similar to controls. Temporal order judgment preceded by synchronous vibration impaired tactile acuity in controls and in PD off medications to similar degrees, but this perceptual impairment by synchronous vibration was not present in PD patients on medications.

These findings suggest that dopamine in PD reduces cortico-cortical connectivity within SI and this leads to changes in tactile sensitivity.

Cytokines, which are involved in immunological responses, play important role in the development and progression of Parkinson's disease (PD). The functional polymorphisms identified in cytokine genes are thought to influence PD risk. However, the findings of studies investigating the association between cytokine gene polymorphisms and PD risk are still controversial. Therefore, we conducted a meta-analysis, in order to investigate the potential associations between cytokine gene polymorphisms and PD.

Studies of PD and cytokine polymorphisms were identified by searches of PubMed and PDGene. Pooled analyses were performed to assess the association between cytokine gene polymorphisms and PD.

Our results indicated a positive association of TNFα -1031 CC genotype in overall analysis(CC vs. TT: OR=3.146; 95%CI: 1.631-6.070, p=0.008; CC vs. CT+TT: OR=3.187; 95%CI: 1.657-6.128, p=0.008), and an Asian subgroup, C variant(OR=1.328; 95%CI: 1.053-1.675, p=0.034) also conveyed an increased PD risk as well as CC genotype (CC vs. TT: OR=3.207; 95%CI: 1.614-6.373, p=0.004; CC vs. CT+TT: OR=3.238; 95%CI: 1.636-6.410, p=0.004). A decreased risk for PD was associated with IL-6-174C allele (OR=0.761; 95%CI: 0.641-0.903, p=0.008) and IL-1RA VNTR 2 allele(OR=0.641; 95%CI: 0.456-0.826 p=0.004). For the polymorphisms of IL-1β C[-511]T, IL-1α C[-889]T, TNFα G[-308]A, and IL-10 G[-1082]A no significant association was found between the gene polymorphisms and PD risk.

Our meta-analysis suggested that gene polymorphisms of TNFα -1031, IL-6-174 and IL-1RA VNTR may be associated with PD risk. However, more large well-designed studies will be necessary to validate our findings.

Little is known about the role of oxidative stress in the pathogenesis of vascular dementia (VaD). The aim of this study was to investigate the biomarkers of oxidative stress in urine, as reflected by 8-hydroxydeoxyguanosine (8-OHdG), 8-isoprostaglandin F2a (8-isoPGF2a) and nitrotyrosine (NT) levels, in a group of well characterized VaD patients and in two control groups of Vascular Not Demented (VaND) patients and healthy subjects.

Ninety-six subjects from the Tianjin municipality in China were recruited. Forty-six patients were in the VaD group, 24 patients with VaND and 26 persons with no signs of cognitive disorder were employed as control groups. Urinary 8-OHdG and 8-isoPGF2a was performed using enzyme-linked immunosorbent assay (ELISA), and urinary NT levels were measured by chemiluminescence detection.

Significantly higher urinary 8-OHdG levels were detected in VaD patients compared to VaND patients and healthy control subjects. In contrast, urinary 8-isoPGF2a levels were significantly lower in VaD patients compared with two control groups. For NT levels, no statistically significant differences were observed among the three groups.

Increased urinary 8-OHdG level was a potential marker of oxidative stress in VaD patients. Furthermore, it is also important to take into account potential confounders in order to improve the identification of changes in the status of oxidative stress as related to VaD.

The aim of this retrospective study was to investigate if elevated C reactive protein (CRP) was related to the stroke severity, and to analyze its different distribution in stroke subtypes.

316 patients with acute ischemic stroke (AIS) were enrolled and had CRP determinations; they were dichotomized as<7 or ≥7mg/L according to the previous report. 128 patients with transient ischemic attack who also had CRP measurements were selected as controls. A possible level-risk relationship between elevated CRP and NIHSS, which considered relatively severe illness as a value≥8, was studied within the AIS group.

CRP was elevated in 21% of the AIS compared to 4% in the control group (p = 0.000). Within the AIS group, patients with CRP levels ≥7mg/L had a significantly increased risk of severe stroke (OR 3.33, 95% CI 1.84-6.00, p =0.00). In subtype stroke, the highest rate of elevated CRP and NIHSS were in those with cardioembolic stroke (CE) using TOAST classification, total anterior circulation infarction (TACI) of OCSP classification and large volume infarction (LVI) of Adams classification; the odds ratio(OR) between elevated CRP and NIHSS was 6.14 (95% CI 1.43-26.44) in CE, 1.714 (95% CI 1.30-2.26) in TACI, 2.32 (95% CI 1.08-4.99) in LVI, and the p value were all below 0.05.

Elevated CRP level can reflect the severity of AIS, which was association with stroke subtype.

Sex differences in the risk factors, presentation and outcome of cerebral venous sinus thrombosis (CVST) are poorly defined, despite a discrepant prevalence between males and females. The proportion of patients on hormonal therapy who develop CVST varies widely. We describe the clinical features, risk factors and outcome by sex and by hormone-related risk factors among a large cohort of patients.

We reviewed records of 108 consecutive patients with CVST at a tertiary hospital in Calgary between 1999 and 2009. Descriptive statistics were used for between group comparisons (men, women with hormone-related risk factors and women without hormone-related risk factors).

Females made up 62% of patients, half of whom were on systemic hormonal therapy. Men and women without hormonal risk factors were older at onset. Oral contraceptive use was the major risk factor in women (45%) while concurrent mastoiditis was the most common predisposing factor in men (27%). Complications were frequent and overall mortality was 6%. Persisting deficits at discharge were more common in men (54% vs. 35% and 32%, p = 0.036). There was a trend for women with hormone-related risk factors to have less residual focal neurologic deficit than the other groups (5% vs. 15% and 17%, p=0.051).

There are differences between sexes in the presentation, risk factors and outcome of patients with CVST.

Awake brain surgery is useful for the treatment of a number of conditions such as epilepsy and brain tumor, as well as in functional neurosurgery. Several studies have been published regarding clinical results and outcomes of patients who have undergone awake craniotomy but few have dealt with related ethical issues.

The authors undertake to explore broadly the ethical issues surrounding awake brain surgery for tumor resection to encourage further consideration and discussion.

Based on a review of the literature related to awake craniotomy and in part from the personal experience of the senior author, we conducted an assessment of the ethical issues associated with awake brain tumor surgery.

The major ethical issues identified relate to: (1) lack of data; (2) utilization; (3) conflict of interest; (4) informed consent; (5) surgical innovation; and (6) surgical training.

The authors respectfully suggest that the selection of patients for awake craniotomy needs to be monitored according to more consistent, objective standards in order to avoid conflicts of interest and potential harm to patients.

Determine if distributed practice of neurological exam (NE) skills in first year medical school produces sustained improvements in the skills of second year students.

A prospective, controlled, non-blinded study conducted at McGill University (class size = 180 students). Expanded teaching of muscle stretch reflexes was provided to first year medical students. A structured examination of muscle stretch reflexes (max score = 100) was administered in second year medical school after a required two week rotation in Neurology. Results for class A (received the intervention in first year) were compared to the results for the preceding class B (had not received the intervention).

77 of 177 (44%) eligible students in class A and 69 of 166 (42%) eligible students in class B participated. Results were analyzed separately for each of two examiners. Mean (SD) scores were 95.2 (5.6) for class A (intervention) and 81.7 (11.1) for class B (control) for the first examiner and 90.4 (8.2) for class A and 83.8 (11.7) for class B for the second examiner. Results were statistically significant (Mann-Whitney test z = 5.27, p < 0.0001 first examiner and z = 2.67, p < 0.0038 second examiner).

Distributed practice of muscle stretch reflexes during first year medical school results in improved performance by second year medical students after their mandatory clinical rotation in neurology, even when examined up to 14 months after the intervention. This finding has implications for the teaching of the NE.