Up to now, many “immunoactive” brain areas have been identified, such a hypothalamic nuclei, brain reward system; but the nucleus ambiguous (Amb), a nucleus nervi vagis of medulla oblongata, was less well studied in neuroimmunomodulation.

In order to obtain more profound comprehension and more knowledge on Amb, we studied the effect of acute electrical stimulation of Amb on thymus and spleen activity in rat. A stimulator was applied to stimulate the Amb of the anaesthetic rats using the parameter at 100μAx5ms x100 Hz every 1s for 1 min. The levels of TGF-β and thymosin-β4 mRNA in thymus, the release of IL-2 and IL-6 at splenocyte in vitro and splenic lymphocyte proliferation were measured at hour 0.5,1,2,3 following the electrical stimulation.

The results showed that concanavalin A (Con A)-induced splenic lymphocyte proliferation and the release of IL-2 and IL-6 were all significantly enhanced at 0.5, 1, and 2 h following effective Amb stimulation as compared to in the control group. However, as compared to in the control group, the levels of TGF-β and thymosin-β4 mRNA in the thymus were both remarkably reduced at 0.5, 1, and 2 h following effective Amb stimulation.

These findings reveal that the Amb participates in the modulation of animal immune functions.

A relationship between migraine and vascular disorders such as hypertension, stroke, and coronary ischemia has been recently reported. Insulin resistance and endothelial dysfunction, which commonly underlies these disorders, have not been widely investigated in migraine patients. In this study, we aimed to investigate the existence of insulin resistance and endothelial dysfunction, and their relationship to vascular risk factors in patients with migraine.

We evaluated insulin resistance and high-sensitivity C-reactive protein (hs-CRP), a marker of endothelial dysfunction, in 60 migraine patients and 25 healthy control subjects. Multiple analysis of covariance test was used to adjust for known confounding factors that can influence insulin metabolism and endothelial function, such as obesity, blood pressure, and lipid parameters.

Insulin resistance, as measured homeostasis model assessment (HOMA)-R levels, was significantly higher in the migraine group (p<0.001). After adjustment for confounding variables, the relationship between migraine and the HOMA-R levels remained significant (p<0.001). The hs-CRP levels did not differ between the migraine and control groups.

Our data show that insulin resistance is present in migraine patients. Endothelial dysfunction is not found during the headache-free period. Further studies are needed to explain the role of insulin resistance in migraine pathogenesis.

Spinal cerebrospinal fluid (CSF) leaks, which are considered a cause of intracranial hypotension, generally do not cause any local symptoms. Although symptoms are key elements for further evaluation, few studies have examined symptom predictors of intracranial hypotension. The aim of this study was to determine what symptoms are predictors of CSF leaks in patients suspected of intracranial hypotension.

We performed radionuclide cisternography in 207 consecutive patients suspected of intracranial hypotension. Intracranial hypotension was suspected when a patient had a history of minor trauma and complained about uncontrolled headache, cranial nerve dysfunction, autonomic dysfunction, or higher brain dysfunction. The leakage of CSF was defined as direct signs of tracer leak into the spinal epidural space or early accumulation of the tracer in the urinary bladder. We obtained information on 16 symptoms commonly reported in previous studies.

CSF leaks were observed in 154 cases (74%). Back pain, limb pain, and limb numbness were inversely associated with CSF leaks (p = 0.042, p = 0.045, and p = 0.006, respectively). In logistic regression analysis, diplopia was a positive predictor of CSF leaks (odds ratio [OR], 6.53; 95% confidence interval [CI], 1.49 to 28.51), whereas limb numbness was a negative predictor (OR, 0.38; 95% CI, 0.17 to 0.84). Of the 21 patients in whom diplopia was present and limb numbness was absent, 20 had CSF leaks (specificity, 98%; positive predictive value, 95%).

Some symptoms may be helpful in the diagnosis of CSF leaks in patients suspected of intracranial hypotension.

1. To determine the awareness of the literature concerning therapeutic manoeuvres in severe closed head injury (CHI) among Canadian critical care clinicians and neurosurgeons, 2. To identify factors that affect utilization of these manoeuvres, and 3. To compare reported appropriateness and frequency of use with #1 and #2.

The study design was a systematic scenario-based survey of all neurosurgeons and critical care physicians treating patients with severe CHI in Canada.

Fifty-nine of 99 neurosurgeons and 82 of 148 critical care physicians responded (57%). The majority of respondents were not able to identify the highest level of published evidence for most manoeuvres, except for the avoidance of corticosteroids (51%). The factor identified by most respondents as being most important in motivating use of any given manoeuvres was the level of published evidence (25%). Although reported appropriateness and frequency of use of most manoeuvres correlated well with each other, they did not correlate with awareness of evidence. In the case of corticosteroids, there was a strong correlation between non-use of steroids and awareness of evidence (R = - 0.30, p = 0.0003).

Respondents to this survey of Canadian physicians treating patients with severe head injury reported published evidence as being the most significant factor affecting use of a therapy. However, most respondents did not correctly identify the highest published level of evidence for most therapies. This study has identified difficulty with research translation that may have clinical implications.

In the province of Quebec, a population-based study of Guillain-Barré syndrome (GBS) was conducted at the time of a mass immunization campaign against meningococcal disease, in 2001.

The study population included residents aged 2 months to 20 years observed from November 1st, 2000 to December 31, 2002, representing 4 075 465 person-years of observation. GBS cases were identified in the provincial hospital database Med-Echo and medical records were reviewed.

Thirty-three incident GBS cases were identified, including 27 cases of acute inflammatory demyelinating polyradiculopathy. The overall GBS incidence rate was 0.8/100 000 person-years, higher in persons aged 1 to 4 years (2.1/100 000) than in those 5 years or more (0.6/100 000). There was a female preponderance and no significant seasonal variation. All patients survived.

Results could be used to interpret reports of adverse events associated with the introduction of new vaccines in this age-group in Canada.

Cognitive dysfunction is one of the common clinical symptoms in multiple sclerosis (MS), but there is no effective treatment for it.

The aim of this study was to evaluate the effect of rivastigmine in treating memory and cognitive dysfunction in MS.

A single-center double-blind placebo-controlled randomized clinical trial conducted from October 2005 to February 2007. Sixty definite MS patients with cognitive impairment age 16 to 54 years were randomly allocated to receive a 12-week treatment course of either rivastigmine (1.5 mg once a day increment over 4 weeks to 3 mg twice daily) or placebo. Response to treatment was assessed by the Wechsler Memory Scale (WMS) at baseline and 12 weeks after start of therapy.

A slight, but significant memory improvement occurred in both groups. Of the 30 patients treated with rivastigmine, the mean (SD) WMS general memory score increased from 60.3 (4.2) at baseline to 64.9 (5.3) at the end of study period (P<0.001). Correspondingly, in the 30 patients treated with placebo, the mean (SD) WMS general memory score increased from 60.5 (4.9) to 64.5 (3.7) (P < 0.001). The average WMS general memory score at the end of trial did not changed between rivastigmine and placebo group (mean difference, 0.4; 95% CI, -2.0, 2.8).

No significant differences were seen between rivastigmine and placebo on the mean (SD) WMS general memory score. A larger multicenter study of rivastigmine in MS is warranted in order to more definitely assess the efficacy of this intervention.

Optical coherence tomography (OCT) - measured retinal nerve fiber layer (RNFL) values may represent a surrogate biomarker for axonal integrity in multiple sclerosis (MS). The purpose of this study was to determine whether RNFL measurements obtained within two years of an optic neuritis (ON) event distinguish patients at increased risk of developing clinically-definite MS (CDMS).

Fifty consecutively sampled patients who experienced a single ON event were followed prospectively for a mean period of 34 months with OCT testing. Values of RNFL in clinically-affected and non-affected eyes were compared between patients who developed CDMS and those that did not develop MS after ON.

Twenty-one patients (42%) developed CDMS during the course of the study, with a mean conversion time of 27 months. Mean RNFL values were thinner in the clinically - affected eyes of non - MS patients than CDMS eyes after one year (p = 0.0462) due to more severe ON events in the former. By year two, CDMS patients manifested more recurrent ON events and RNFL thinning than non - MS patients. Temporal RNFL values were thinner in the non-affected eyes of CDMS patients with a trend towards significance (p = 0.1302).

Our results indicate that RNFL thickness does not reliably distinguish patients at higher risk of converting to CDMS after ON. The severity of ON has a greater effect on RNFL thickness than risk of CDMS at one year. The CDMS patients demonstrate progressive RNFL thinning likely due to recurrent sub-clinical ON events, which may help differentiate them from non - MS patients over time.

Parkinsonism (PD) is occasionally seen in several types of spinocerebellar ataxia (SCA). Mutations in SCA gene have been reported in the patients of parkinsonism without ataxia.

We examined spinocerebellar ataxia type 12 mutation in 877 PD and 199 multiple system atrophy (MSA) patients.

No patients showed abnormal SCA12 expansion. It suggests that PD and MSA are not associated with SCA12 and it is not necessary to screen SCA12 in PD and MSA patients.

Multiple sclerosis (MS) is believed to be an autoimmune disease occurring in genetically predisposed individuals after an appropriate environmental exposure such as viral infections. Recent studies suggest a significant association between MS and the functional 5’-(GT)n polymorphism in the promoter region of the NRAMP1 gene. In the present study we aimed to evaluate the contribution of the allelic variation in the NRAMP1 promoter to MS susceptibility and to study the role of viral infection in relation to specific NRAMP1 genotypes, in a Sardinian cohort.

Sixty MS patients and 66 healthy individuals were genotyped, and screened for the presence of Epstein-bar virus (EBV) and JC virus (JCV) sequences.

Consistent with previous autoimmune disease studies, allele 3 at the functional 5’(GT)n promoter region repeat polymorphism, was significantly overrepresented among MS patients when compared to controls (p=0.02). The EBV and JCV sequences were detected in 8/60 (13.33%) and in 4/60 (6.66%) of MS patients respectively and in 5/66 (7.57%) and in 0/66 of controls.

The allelic variation in the NRAMP1 promoter may contribute to MS susceptibility in the Sardinian population. The viral sequences were not confined to a specific NRAMP1 genotype.

Chiari type II malformation (CII) is a developmental anomaly of the cerebellum and brainstem, which are important structures for processing the vestibulo-ocular reflex (VOR). We investigated the effects of the deformity of CII on the angular VOR during active head motion.

Eye and head movements were recorded using an infrared eye tracker and magnetic head tracker in 20 participants with CII [11 males, age range 8-19 years, mean (SD) 14.4 (3.2) years]. Thirty-eight age-matched healthy children and adolescents (21 males) constituted the control group. Participants were instructed to ‘look’ in darkness at the position of their thumb, placed 25 cm away, while they made horizontal and vertical sinusoidal head rotations at frequencies of about 0.5 Hz and 2 Hz. Parametric and non-parametric tests were used to compare the two groups.

The VOR gains, the ratio of eye to head velocities, were abnormally low in two participants with CII and abnormally high in one participant with CII.

The majority of participants with CII had normal VOR performance in this investigation. However, the deformity of CII can impair the active angular VOR in some patients with CII. Low gain is attributed to brainstem damage and high gain to cerebellar dysfunction.

The purpose of this study was to determine whether tasks involving effortful attention would cause augmentation of rigidity in patients with mild Parkinson disease.

In 17 subjects with mild Parkinson disease, rigidity in a single arm was assessed during various experimental conditions by a blinded movement disorders neurologist. Rigidity was scored separately at the wrist and the elbow using an ordinal scale. In three of the conditions, sustained attention was directed toward visual, auditory or movement-related stimuli. Two varieties of Froment maneuver served as positive controls: contralateral hand opening-closing or ipsilateral foot tapping. In addition, rigidity was assessed twice with subjects resting. The examiner was unaware of the sequence of experimental conditions and this was changed for each subject. Mean rigidity scores for the various experimental conditions were compared against the baseline state (an average of both trials with the patient resting) using a repeated measures ANOVA and post-hoc Tukey-Kramer multiple comparisons test.

Rigidity was significantly increased from baseline with each of the attentional tasks (p <0.01 to p <0.001) and also with the two Froment maneuvers (p <0.001). Rigidity augmentation with contralateral hand opening-closing was significantly greater than with any of the attentional tasks (p <0.05 to p <0.001).

Tasks of effortful attention did appear to augment rigidity in patients with mild Parkinson disease. We speculate that the greater augmentation seen with the Froment maneuver could have an anatomic basis.