Propionibacterium acnes (P. acnes) is a relatively avirulent organism that is part of the normal skin flora. Most patient isolates are considered contaminants but, in a small subset of patients, particularly in the post-neurosurgery setting, the organism can cause significant infections. We reviewed our experience with the occurrence and management of P. acnes infections after cranial neurosurgical procedures over a five-year period.

Patients with positive cultures for P. acnes between 1996 and 2001 were identified by review of the Saskatoon Health Region microbiology laboratory database. Of the 141 positive cultures, a review of hospital records identified six patients with P. acnes infections after neurosurgical procedures. A review of the literature related to P. acnes associated CNS infections was conducted.

All patients had undergone a craniotomy or burrhole placement, and one patient had received prior radiotherapy. There were no P. acnes-related ventriculoperitoneal shunt infections. All patients presented with scalp swelling and three had purulent discharge. Symptoms occurred more than two months after the initial surgery in five of six patients, while one patient developed symptoms three years post-operatively. Management for all patients included removal of the craniotomy flap and treatment with parenteral antibiotics, followed in most cases by oral antibiotics. A good response without relapse of infection was seen in five patients; one patient had recurrent infection after cranioplasty.

P. acnes is a rare but important cause of infection after craniotomy. Wound debridement, removal of the bone flap and adequate antibiotic coverage result in cure in the majority of patients.

Although randomized controlled trials (RCTs) are the gold standard for evaluating therapeutic interventions, surgical RCTs are particularly challenging and few have been done in the field of epilepsy surgery. We assess the level of RCT activity in epilepsy surgery and propose feasible alternatives to develop sustainable research initiatives in this area.

We undertook a systematic review of the world literature to assess the level of RCT activity in epilepsy surgery. Previous personal experience with RCTs in epilepsy surgery and examples of successful Canadian multicentre research networks were reviewed to propose initiatives for sustainable, valid research in epilepsy surgery.

We identified 12 RCTs in epilepsy surgery, including 692 patients, of whom 416 were involved in vagus nerve stimulation, 16 in various brain electrostimulation procedures, 180 in comparisons of different surgical techniques, and 80 in a comparison of medical versus surgical therapy. Most studies were of short duration (median = 3 months, range 3-12 months). In the area of resective surgery, only temporal lobe epilepsy has been subjected to any type of RCT comparison. All RCTs have been done within the last 13 years. There were no multicentre Canadian surgical studies.

The adoption of RCTs in epilepsy surgery has been slow and difficult worldwide. Because of its universal health care system and its well established epilepsy surgery centres, Canada is in a strong position to create a national epilepsy surgery research initiative capable of undertaking high quality, sustainable research in epilepsy surgery.

Saccadic adaptation corrects errors in saccadic amplitude. Experimentally-induced saccadic adaptation provides a method for studying motor learning. The cerebellum is a major participant in saccadic adaptation. Chiari type II malformation (CII) is a developmental deformity of the cerebellum and brainstem that is associated with spina bifida. We investigated the effects of CII on saccadic adaptation.

We measured eye movements using an infrared eye tracker in 21 subjects with CII (CII group) and 39 typically developing children (control group), aged 8-19 years. Saccadic adaptation was induced experimentally using targets that stepped horizontally 12º to the right and then stepped backward 3º during saccades.

Saccadic adaptation was achieved at the end of the adaptation phase in participants in each group. Saccadic amplitude gain decreased by 6.9% in the CII group and 9.3% in the control group. The groups did not differ significantly (p = 0.27). Amplitude gain reduction was significantly less in the CII participants who had multiple shunt revisions. Regression analyses revealed no effects of spinal lesion level, presence of nystagmus, or cerebellar vermis dysmorphology on saccadic adaptation.

The neural circuits involved in saccadic adaptation appear to be functionally intact in CII.

Blood pressure is elevated in most patients during acute ischemic stroke, but the prognostic significance of this is unclear as the current data yield conflicting results.

Admission blood pressure from the 1281 patients in the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) was analyzed for prognostic significance as well as the risk of hemorrhagic transformation. We also examined weighted-average blood pressure over seven days, and the impact of a 30% change in blood pressure in 24 hours. Patients with severe hypertension were excluded from the TOAST trial.

Increasing systolic blood pressure (SBP) on admission, but not diastolic (DBP) or mean arterial pressure (MAP) was predictive of poor outcome, but this effect was not significant after adjustment for other know prognostic factors. Increasing weighted-average SBP and MAP over seven days were predictive for poor outcome, but a 30% change in blood pressure over 24 hours was not.

Admission blood pressure is not an independent prognostic factor in acute ischemic stroke, but the weighted-average of SBP and MAP over seven days probably does have predictive value with higher values having a worse prognosis. A prospective trial of blood pressure control during acute stroke is needed.

Ontogenic development of granule cells in the hippocampal dentate gyrus is influenced by genes including WNT3, EMX2, NEUROD, and LEF1. Dentate granule cells continue to be generated from stem cell precursors postnatally and during adult life, and are implicated in normal and abnormal neurological function. Developmental privation of dentate granule cells is rare and essentially always occurs in the context of other neurodevelopmental abnormalities. We have found no previous reports of severe, selective agenesis of dentate granule cells in humans.

A gross and microscopic examination of the brain included appropriate histochemical and immunohistochemical preparations and examination of the hippocampal formation at multiple levels bilaterally.

This neurologically normal 82-year-old man was found to have bilateral agenesis of the hippocampal dentate gyrus, no identifiable dentate granule cells, and moderate disorganization of the pyramidal cell layer of Ammon's horn. We found no neurodevelopmental abnormalities outside the hippocampus.

The hippocampal architectural alterations in this patient are similar to those associated with a murine Lef1 mutation, but our human case does not have the other congenital deficits reported in the Lef1-null mouse. Bilateral agenesis of the hippocampal dentate gyrus, and apparent failure of regeneration of dentate granule cells from stem cells in adult life, may occur without overt clinical neurological deficits.

Middle-latency somatosensory evoked potentials (SEPs) following median nerve stimulation can provide a sensitive measure of cortical function. We sought to determine whether the mechanical forces of whiplash injury or concussion alter normal processing of middle-latency SEPs.

In a cross-sectional pilot study 20 subjects with whiplash were investigated (50% between 0.5-2 months and 50% between 6-41 months post injury) and compared to 83 healthy subjects using a standard middle-latency SEP procedure. In a subsequent prospective study subjects with either acute whiplash (n=13) or Grade 3 concussion (n=16) were investigated within 48 hours and again three months post injury.

In the pilot study the middle-latency SEP component N60 was significantly increased in the ten subjects investigated within two months after whiplash. In contrast, the ten subjects examined more than six months after injury showed normal latencies. In the prospective study N60 latencies were increased after whiplash and concussion when tested within 48 hours of injury. At three months, latencies were improved though still significantly different from controls post whiplash and concussion.

Both whiplash injury and concussion alter processing of the middle-latency SEP component N60 in the acute post traumatic period. The acute changes appear to normalize between three-six months post injury. The SEP similarities suggest that the overlapping clinical symptomatology post whiplash and concussion may reflect a similar underlying mechanism of rotational mild traumatic brain injury.

We report the case of a 58-year-old female with clinical, radiological, and histopathological evidence of Rasmussen's encephalitis, representing the oldest confirmed case to date.

The patient presented with complex partial seizures characterized by numbness of the left face and staring spells. These progressed to a state of epilepsia partialis continua with jerking of the left face, as well as severe cognitive impairment and loss of all communication. The patient responded well to Intravenous Immunoglobulin (IVIG) therapy despite early complications and with ongoing treatment is living independently with minimal cognitive impairment.

This represents the oldest confirmed case of Rasmussen's encephalitis and suggests that this diagnosis should be considered in patients of any age with an appropriate clinical picture. We recommend IVIG as a first line therapy for adult cases of Rasmussen's encephalitis.

It is unclear whether medical or invasive (surgical or catheter interventional) treatment is preferable to prevent recurrence of cerebral ischemia in patients with patent foramen ovale (PFO) as the suspected cause of stroke and what the role of concomitant risk factors is in stroke recurrence.

Over a period of ten years, 124 patients (mean age 51 ± 15 years) with cryptogenic cerebral ischemia and PFO were included into the study and prospectively followed over a mean of 52 ± 32 months. Of these, 83 were treated medically, 34 underwent transcatheter closure, and seven had surgical closure of the foramen. Of the medically treated patients, 11 stopped medication during follow-up. Recurrent ischemic events and risk factors for recurrence were analyzed.

Annual stroke recurrence rates were generally low and comparable in catheter and medically treated patients, and in patients who had stopped medication (2.9%/2.1%/2.2%/year). Patients suffering from recurrence after transcatheter closure (n=2) both had residual shunts. No stroke recurrence was observed in the few surgically treated patients. An atrial septal aneurysm was not a predictor of recurrent or multiple strokes (p>0.05, OR=0.31, and OR=0.74). Large shunts and a history of previous ischemic events were considerably more frequent in patients with recurrent strokes (p<0.05, OR=5.0, and OR=4.4). Pulmonary embolism and case fatality rates were significantly higher in patients with stroke recurrence (p<0.001, and p<0.01).

The absolute risk of recurrent cerebrovascular events in patients with PFO receiving medical or catheter interventional therapy is low. The small group of untreated patients had a comparably low rate of stroke recurrences. Previous ischemic events and shunt size were risk factors in this observational study. Given conflicting findings across multiple studies, enrollment into a randomized controlled trial would be the optimal choice.

Behcet's disease is a multisystemic vascular inflammatory disorder of unknown origin. It is relatively rare and central nervous system involvement is seen in 5% of affected individuals. Somatosensory evoked potentials (SEPs) can provide information that shows the presence of clinically unsuspected lesions in the central nervous system of these patients. However, the effects of changing the stimulus frequencies on latencies of SEP potentials and central conduction time (CCT) in patients with neuro-Behcet's disease (NB) have not been studied yet. In this study, our aim was to reveal these effects to investigate whether the change of stimulus frequencies could be of convenient use in obtaining more accurate CCT estimations in SEP studies of these patients.

We performed median nerve SEPs of 14 patients with NB and 15 healthy volunteers. We changed the stimulus frequency: 2 Hz, 4Hz, 6Hz and 9Hz in successive recordings and statistically compared the changes on SEP potentials and peak and onset CCT in the neuro-Behcet (NB) group and the normal group.

Our results indicated that the onset CCT values of the NB group were higher than the normal group at 4Hz and 9Hz stimulations. However, the comparison of peak CCT in the NB group and the normal group did not show any statistically meaningful differences at all stimulation frequencies.

Onset CCT has not been measured before in former SEP studies of patients with NB. We highly recommend measuring onset CCT at higher stimulation frequencies in order to reveal central conduction time pathologies in these patients.

Mothers of children with intractable epilepsy are generally stressed and experience more emotional problems. Fatigue may affect their productivity, social interactions, and their ability to adequately take care of their children. The objectives were to examine the relationship between intractable childhood epilepsy and maternal fatigue, and explore possible contributing factors.

Sixty-four consecutive mothers of children with intractable epilepsy were identified prospectively. Exclusion criteria included degenerative/metabolic disorders or life threatening illness, such as brain tumors. Fatigue was measured using a standardized 11-item questionnaire, which has been revalidated in an Arabic speaking population.

Mothers' ages were 24-45 years (mean 34) and ages of their epileptic children were 1-15 years (mean 6.7). Most children (64%) had epilepsy for >2 years, were on >1 antiepileptic drug (AED) (72%), and had daily seizures (47%). Thirty-four (54%) of the children had motor deficits and 83% had mental retardation (severe in 41%). Twenty-eight (44%) mothers were fatigued. Factors associated with increased maternal fatigue included child's age <2 years (p=0.01), cryptogenic epilepsy (p=0.03), and severe motor deficits (p=0.04). Factors associated with lowered fatigue included performing regular exercise (p=0.006), lack of mental retardation (p=0.01), seizure control (p=0.05), using one AED (p=0.002), infrequent ER visits (p=0.005), and lack of recent hospitalization (p=0.005).

Mothers of children with intractable epilepsy are increasingly fatigued. Several correlating factors were identified, mostly related to seizure control, mental and physical handicap. Strategies to manage the problem include proper education, seizure control, participation in regular exercise, social support, and psychological counseling.

To identify the impact of private insurance coverage on discharge disposition after a traumatic brain injury (TBI) using injury in a motor vehicle accident (MVA) as a proxy for private insurance, controlling for age and severity of injury.

Cross-sectional study.

Patients with TBI discharged between 1993-1994 and 2000-2001 (n = 9,703).

Discharge destination from acute care; controlled odds ratio (OR) and confidence interval (CI) for type of injury.

Type of injury, age, and length of stay are significantly associated with discharge destination. However, the motor vehicle accident patients are 56% more likely to be discharged to home with support services than patients with similar injuries from falls.

Even in a system with universal coverage, availability of private insurance type is a potential independent determinant of postacute care services. More research is required to determine the effect this relationship has on the cost and outcomes of care for TBI patients.

Charcot-Marie-Tooth (CMT) disease is the most common form of inherited motor and sensory neuropathy. Based on neurophysiological and neuropathological criteria CMT has been sub-classified into two main types: demyelinating and axonal. Furthermore, it is genetically heterogeneous with autosomal dominant, autosomal recessive (AR) and X-linked modes of inheritance. Thus far, seven genes have been identified in association with the demyelinating AR-CMT disease. We hereby report our clinical and molecular genetic findings in a consanguineous family with AR-CMT.

Two young sisters with AR-CMT and other non-affected family members were clinically and electrophysiologically evaluated and then molecular genetic investigation was carried out in order to identify the pathogenic mutation.

Following an initial indication for linkage of the family to the CMT4A locus on chromosome 8, we sequenced the Ganglioside-induced differentiation-associated protein 1 (GDAP1) gene and identified a single nucleotide deletion in exon 3 that is associated with AR-CMT in the family.

We identified a novel GDAP1 439delA mutation that is associated with AR-CMT in a consanguineous family of Iranian descent with two affected young girls and a history in other members of the family.

Referral of movement disorder patients for deep brain stimulation surgery was examined to determine whether referred patients were representative of gender proportions in our population, and reasons why patients do not proceed to surgery.

Demographic information on referrals to the surgical program was retrospectively reviewed from our database and from a detailed chart review.

Although almost equal numbers of movement disorder patients are male and female, of the 91 patients referred for surgery, only 31% were female. Sixty-one percent of referred patients did not undergo surgery. Of these, the majority were denied for medical reasons, including cognitive decline (21%), psychiatric concerns (5%) and neurological reasons (42%).

Almost one-third of patients referred for movement disorder surgery were denied for medical reasons. This underscores the importance of evaluation of all potential patients by a multidisiplinary team to fully assess suitablity for stereotactic surgery. Interestingly, women were under-represented in those referred. In order that all appropriate patients have the opportunity to consider surgery, education of both physicians and patients, and different strategies to approach females regarding surgery may allow more patients to benefit from this treatment.

Neurofibromatosis type 2 (NF2) is an autosomal dominant disease predisposing individuals to the risk of developing tumors of cranial and spinal nerves. The NF2 tumor suppressor protein, known as Merlin/Schwanomin, is a member of the protein 4.1 superfamily that function as links between the cytoskeleton and the plasma membrane.

Upon selective extraction of membrane-associated proteins from erythrocyte plasma membrane (ghosts) using low ionic strength solution, the bulk of NF2 protein remains associated with the spectrin-actin depleted inside-out-vesicles. Western blot analysis showed a ~70 kDa polypeptide in the erythrocyte plasma membrane. Furthermore, quantitative removal of NF2 protein from the inside-out-vesicles was achieved using 1.0 M potassium iodide, a treatment known to remove tightly-bound peripheral membrane proteins.

These results suggest a novel mode of NF2 protein association with the erythrocyte membrane that is distinct from the known membrane interactions of protein 4.1. Based on these biochemical properties, several purification strategies were devised to isolate native NF2 protein from human erythrocyte ghosts. Using purified and recombinant NF2 protein as internal standards, we quantified approximately ~41-65,000 molecules of NF2 protein per erythrocyte.

We provide evidence for the presence of NF2 protein in the human erythrocyte membrane. The identification of NF2 protein in the human erythrocyte membrane will make it feasible to discover novel interactions of NF2 protein utilizing powerful techniques of erythrocyte biochemistry and genetics in mammalian cells.