Alzheimer's Disease (AD) is characterized in part by the increased presence of neurofibrillary tangles and amyloid beta (Aβ) plaques. Alzheimer's Disease is considered an inflammatory disease and, as such, nuclear factor-kappaB (NFκB) plays an important role in the pathophysiology of AD. Insulin acts as a neurotrophic factor. Yet, in the context of insulin resistance, concomitant hyperinsulinemia may contribute to the pathogenesis of AD.

Rat Primmary Hippocampal Neurons (RPHN) were treated with insulin in the absence and presence of Wortmannin and ERK5 small inhibitory RNA and assayed for downstream effectors of activated ERK5.

Here we demonstrate that genetic inhibition of ERK5 blocks insulin stimulated (1) activation and translocation of ERK5 and NFκB, (2) phosphorylation of IKKα via association with ERK5, (3) increases in Aβ1-40 and Aβ1-42 soluble proteins 3-fold and 2.2-fold, respectively, and (4) increases in tau phosphorylation in RPHN.

ERK5 plays an active role in insulin signaling in neurons and may be a potential therapeutic target for neurodegenerative diseases.

The long-term outcome after lumbar microdiscectomy (LMD) may be affected by low back pain (LBP) and segmental instability, the determinants of which remain unclear. We sought to analyze the interaction between clinical, functional, and radiological variables and their impact on patient outcome.

All patients who underwent LMD in 2004-2005 were invited to participate in this retrospective cohort study. Patients were re-evaluated clinically and radiologically after a three to five year follow-up.

Forty-one of 97 eligible patients were enrolled. Twelve patients (29.3%) reported moderate-to-severe sciatica, 12 (29.3%) had moderate LBP, and 13 (31.7%) exhibited clinical evidence of segmental instability. Thirty-eight patients (92.7%) had minimal disability and 3 (7.3%) had moderate disability. Twenty-three patients (56.1%) were fully satisfied, while 18 (43.9%) had only partial satisfaction, having expected a better outcome. Thirty-three patients (80.5%) returned to full-time work. Median disc space collapse (DSC) was 20% (range 5-66%) and L4-L5 was particularly affected. Prevalence of Modic changes increased from 46.3% to 78% with type 2 predominance. Multivariate logistic regression analysis identified the following negative prognostic factors: female sex, young age, lack of regular exercise, and chronic preoperative LBP. There was no correlation between the course of Modic changes, DSC, and patient outcome.

Although many patients may be symptomatic following LMD, significant disability and dissatisfaction are uncommon. Female sex, young age, lack of exercise, and chronic preoperative LBP may predict a worse outcome. Disc collapse is a universal finding, particularly at L4-L5. Neither DSC nor Modic changes seem to affect patient outcome.

Minimally invasive posterior cervical foraminotomy for radicular symptoms has become more prevalent. The reported experience with microscopic tubular assisted posterior cervical laminoforaminotomy (MTPF) for the treatment of radicular pain is lacking. Tubular assisted techniques have been considered to offer significant benefit, over open procedures, in terms of minimizing tissue damage, operative time, blood loss, analgesic requirements and length of hospital stay. We hypothesized that MTPF reduces post-operative analgesic requirements and length of hospital stay over the traditional open laminoforaminotomy, with no difference in complication rates and, secondly, that MTPF is comparable to endoscopic posterior foraminotomy (EPF).

We conducted a retrospective review of 107 patients who underwent posterior cervical laminoforaminotomy for radicular pain between 1999 and 2009. Patient demographics, intra-operative parameters, length of hospitalization, post-operative analgesic use, complications and short-term neurological outcome were compared between groups.

Between 1999 and 2009, a total of 107 patients were identified to have undergone a cervical foraminotomy. An open approach was used in 65 patients, while 42 underwent MTPF. Operative time and complications were comparable between groups. Significant differences favoring MTPF were observed in operative blood loss, post-operative analgesic use and length of hospital stay (p<0.001). All results were comparable to previous reports utilizing EPF.

MTPF for the treatment of cervical radiculopathy significantly reduces blood loss, post-operative analgesic use and length of hospital stay compared to the standard open approach. Operative time and complication rates were comparable between both techniques, whilst MTPF offered similar results compared to EPF.

Carpal tunnel syndrome and ulnar nerve entrapment at the elbow are the most common entrapment neuropathies seen in adults. Surgery for nerve decompression is a safe and effective treatment option, and is usually performed under local anesthesia and as an outpatient procedure. This study aimed to explore patients' satisfaction and other aspects of the overall experience with this type of surgery.

Qualitative research methodology was used. Semi-structured, open-ended interviews were conducted with 30 adult patients who had undergone carpal tunnel release or ulnar nerve decompression at the elbow 6-24 months prior. Interviews were digitally audio recorded and transcribed, and the data subjected to thematic analysis.

Four overarching themes emerged from the data: (1) most patients did not perceive their condition to be serious; (2) patients were satisfied with the overall surgical experience; (3) the outcome was more important to patients than the process; and (4) majority of patients had a realistic expectation of outcomes.

Patients had a positive experience with carpal tunnel and ulnar nerve decompression surgery, although their level of satisfaction was dependent on the surgical outcome. Areas requiring improvement, specifically information about post-operative care and expectations of recovery, will be implemented in the future care of patients.

Retrospective study assessing the efficacy and tolerability of vagus nerve stimulation (VNS) for the treatment of refractory epilepsy at Notre-Dame Hospital.

Chart review of all adult epileptic patients treated by VNS with ≥ 1 year follow-up. Responders were defined as patients with ≥ 50% reduction of baseline seizure frequency.

Thirty-four patients (14M; mean age = 29.9 yrs) received a VNS. Sub-pectoralis implantation (n = 25) was more frequent than subcutaneous (n = 9). Most patients suffered from intractable partial epilepsy. After 6 months, 12 months, 24 months, and 36 months, 14/34 patients (41%), 16/34 patients (47%), 17/30 patients (57%) and 12/20 patients (60%) respectively were responders. Two patients (6%) became seizure-free. Complications related to implantation were minor: eight cases of limited cervical hypoesthesia, two minor scar infections and one Horner syndrome. Adverse events (voice hoarseness, throat paresthesia, coughing) related to stimulation were generally mild and tended to wane over time. However, a reduction in seizure frequency did not translate into a reduction in medication, as only 9% of responders had less antiepileptic medication at last follow-up compared to baseline.

VNS as practiced at Notre-Dame hospital is an efficacious and safe treatment for refractory epilepsy. Quotas allotted to epilepsy centers in the province of Quebec should be lifted or increased to allow more patients to benefit from this therapeutic device.

In order to characterize the nature and extent of neuropsychological dysfunction in primary lateral sclerosis (PLS), we studied prospectively cognitive, emotional, and behavioral functioning in PLS, and compared performances to functioning in amyotrophic lateral sclerosis (ALS).

Eighteen patients with PLS and 13 patients with ALS completed a neuropsychological test battery assessing both cognitive skills and emotional/behavioral functioning.

Both PLS and ALS groups scored broadly within normal limits (mean T-scores greater than 40) on all cognitive measures and no significant between-group differences were found with the exception of one variable. However, when examined on a case by case basis, the data revealed considerable heterogeneity amongst patients in both groups. Overall, 39% of PLS patients and 31% of ALS patients were considered cognitively impaired. A higher than expected frequency of abnormal scores was noted for several tests of executive function in both groups, and a majority of PLS patients also exhibited abnormal behavioural symptoms. There was no relationship in PLS or ALS groups between cognitive functioning and disease duration, current site of disease, site of onset, functional status, and respiratory variables. Comparison between the PLS and ALS groups indicated virtually no differences in cognitive test scores and overall emotional/behavioural symptoms.

We observed deficits in cognition and behaviour in a significant proportion of PLS patients which were comparable to those observed in ALS cases. Although deficits were not in the range of frontotemporal dementia, both ALS and PLS cases demonstrated deficits most prominently on tests of executive functioning.

Octogenarians were excluded from participation in many carotid endarterectomy trials due to the high complication rates observed in past studies. However, stroke resulting from carotid stenosis is expected to increase with the aging population. Moreover, advances in Carotid Angioplasty and Stenting (CAS) techniques have resulted in perceived improved safety of this procedure. We sought to review our experience with carotid stenting in symptomatic octogenarians with an emphasis on short-term outcomes and complications.

This is a retrospective longitudinal cohort study of all symptomatic patients who underwent CAS in our center between 1997 and 2007. Thirty-day stroke and death rates, and length of hospitalization were compared between the symptomatic octogenarians and non-octogenarians.

A total of 214 procedures were performed on 211 symptomatic patients (56 females). Fifty-nine patients (14 females) were octogenarians. The median (interquartile range) age on procedure date for the octogenarian cohort was 83 (4) years. Periprocedural death occurred in two (3.4%) octogenarians and five (3.3%) non-octogenarians (p = 0.97). At 30 days from the procedure, stroke occurred in four (6.8%) octogenarians and seven (4.6%) non-octogenarians (p= 0.52). The mean hospital stay (4.8 days) was not different between the two cohorts. Age was not a predictor of the 30-day risk of composite stroke or death.

The complications rate observed in octogenarians was not significantly higher than non-octogenarians. Our findings suggest that octogenarians should be included in randomized trials examining CAS to better define the risk-benefit profile of this procedure in the elderly.

Normal-pressure hydrocephalus (NPH) is characterized by gait disturbance, cognitive impairment, with or without urinary incontinence, enlarged ventricles with or without cerebral atrophy and normal cerebrospinal fluid pressure.

We report two sisters with NPH who lived together their entire lives and whose natural history might provide insights into genetic and environmental mechanisms underlying this disorder. Both patients were in their early seventies, single, had similar daily habits and hypertension. No other family members had NPH.

They both underwent shunt placement and showed improvement documented by history and neuropsychological assessment. Both showed a delayed deterioration due to vasculopathy. Both patients were homozygous for the apolipoprotein E (ApoE) e3 allele on chromosome 19. No environmental factors that might have influenced the development of NPH were identified.

Our report of two sisters with NPH may indicate the presence of genetic predisposition and further studies involving genetics and environmental factors are necessary to elucidate their role in the pathogenesis of NPH.

Repetitively discharging neurons in epileptic foci have a high energy requirement that might be demonstrated histochemically as increased mitochondrial enzymatic activity in brain resections for epilepsy in children.

Frozen sections were studied histochemically of 10 brain resections from 7 epileptic children, 2 months to 17 years of age. None had mitochondrial disease. Three patients had tuberous sclerosis (TS) or hemimegalencephy (HME). Tissues included hippocampus and neocortex. Oxidative enzymes were studied for respiratory chain complexes I, II, IV, using the muscle biopsy protocol. In addition, immunoreactivities of α-B-crystallin and transmission electron microscopy (EM) were performed.

Oxidative activities were variable in adjacent neurons within a field: a minority were intense, adjacent to neurons with weaker mitochondrial activity exhibiting poor contrast of the soma because of similar oxidative activity in surrounding neuropil. Endothelium of vessels uniformly exhibits strong activity. Alpha-B-crystallin reactivity was strong at these foci. EM confirmed an abundance of neuronal mitochondria with normal cristae. In TS and HME, many dysplastic neurons showed intense activity; balloon cells had sparse activity.

Histochemistry of mitochondrial oxidative enzymes reveals scattered and clustered neurons with stronger activities than others at epileptic foci. Such intensely staining neurons may be functionally “hypermetabolic” but they do not signify mitochondrial disease. Individual intensely stained neurons might be epileptogenic, but do not denote an epileptogenic field in the same manner as α-B-crystallin, which also was strongly reactive in these foci.

Multiple sclerosis (MS) is a disease with purported environmental causes. Consistent correlations have been found in various settings for latitude, smoking exposure, sunlight, and vitamin D deficiency. We analysed the contribution of various environmental factors to the risk of developing MS from a population perspective.

We collated global data of MS prevalence from 54 studies over the previous ten years and calculated the degree of risk contributed by latitude, longitude, ultraviolet radiation (from NASA satellite data and formulae for available sunlight hours), population smoking rates (from WHO data), gender, study date, study demographics, and several socioeconomic factors. We report a very significant negative correlation between MS prevalence and available ultraviolet (UV) radiation.

The lack of available UV radiation outweighs other factors by at least 20 fold (p<10∧-8) from single variate regression analysis. Multiple regression analysis revealed that latitude and longitude are also significant factors; smoking may also provide a very minimal role. The eight prevalence studies from Scandinavia produced prevalences that were lower than expected, given their global geospatial positioning.

The available ultraviolet radiation is a significant environmental factor, moreso than all the other factors examined.

To determine if there is a correlation between cerebellar tonsillar descent in patients with and without Chiari I malformation and three skull morphometric measurements: clivus length, anteroposterior diameter of the foramen magnum, and Boogard's angle.

Cerebellar tonsillar descent, clivus length, anteroposterior diameter of the foramen magnum, and Boogard's angle were measured in mid-sagittal T1-weighted magnetic resonance images of 188 patients. The study included 81 patients with Chiari I malformations (CMI). Without identifiable pathology, 107 patients served as a comparison group. Two-sample t-tests were used to assess for significance. A Pearson correlation matrix was constructed to assess the strength of linear dependence between measured parameters for the study population.

A negative correlation was found between tonsillar herniation and clivus length (r = -0.30, P < 0.001), while a positive correlation was found between tonsillar herniation and foramen magnum size (r = 0.15, P = 0.0431), and Boogard's angle (r = 0.23, P = 0.0014). Clivus length was shorter (P = 0.0009) in CMI patients (4.02 cm ± 0.45) than comparison patients (4.23 cm ± 0.42). In addition, the anteroposterior diameter of the foramen magnum was wider (P = 0.0412) (3.74 cm ± 0.40 compared to 3.63 ± 0.30) and Boogard's angle was larger (P = 0.0079) (123.58 degrees ± 8.27 compared to 120.62 degrees ± 6.79) with CMI.

A greater degree of cerebellar tonsillar herniation is associated with a shorter clivus length, a wider anteroposterior diameter of foramen magnum, and a wider Boogard's angle.

To determine if different methods of evaluating cognitive change over time yield measurably different outcomes.

Twelve cognitively impaired patients with clinically definite Multiple sclerosis (10 relapsing-remitting, 2 secondary progressive) underwent neuropsychological testing (baseline, 6, 12 months). Data was analysed using: t-tests evaluating group differences on individual tests, group differences in composite scores, reliable change analyses at the level of the individual, and comparisons regarding number of tests failed at each time point.

Group t-tests on individual tests yielded no change. When tests were grouped according to theoretical constructs, analyses revealed change in processing speed. Reliable change estimates revealed that 16% of the sample deteriorated. When change was measured with respect to the number of domains affected at each time point, 58% of the sample deteriorated on at least one subtest.

Methodology has a significant impact on interpretation of longitudinal data. In the same group of subjects, traditional group analyses documented no change in individual test scores or change on a single composite score. Analyses of individual results documented change from 16 to 58% of the sample. Advantages and disadvantages of each method were discussed. Findings have implications for interpretation of longitudinal studies.

Damage to the central nervous system by Multiple Sclerosis (MS) leads to multiple symptoms, including weakness, ambulatory dysfunction, visual disturbances and fatigue. Heat can exacerbate the symptoms of MS whereas cooling can provide symptomatic relief. Since the head and neck areas are particularly sensitive to cold and cooling interventions, we investigated the effects of cooling the head and neck for 60 minutes on the symptoms of MS.

We used a double blinded, placebo controlled, cross-over study design to evaluate the effects of head and neck cooling on six heat-sensitive, stable, ambulatory females with MS (Extended Disability Status Scale 2.5-6.5). To isolate the effects of perceived versus physiological cooling, a sham cooling condition was incorporated, where subjects perceived the sensation of being cooled without any actual physiological cooling. Participants visited the clinic three times for 60 minutes of true, sham, or no cooling using a custom head and neck cooling hood, followed by evaluation of ambulation, visual acuity, and muscle strength. Rectal and skin temperature, heart rate, and thermal sensation were measured throughout cooling and testing.

Both the true and sham cooling elicited significant sensations of thermal cooling, but only the true cooling condition decreased core temperature by 0.37°C (36.97±0.21 to 36.60±0.23°C). True cooling improved performance in the six minute walk test and the timed up-and-go test but not visual acuity or hand grip strength.

Head and neck cooling may be an effective tool in increasing ambulatory capacity in individuals with MS and heat sensitivity.