Background: We present clinical and MRI features of progressive ataxia and palatal tremor (PAPT). Case Report: A 67 year-old gentleman visiting from Vietnam presented with intermittent stroke-like episodes consisting of facial weakness, dysarthria, and osillopsia. He reported gradually worsening ataxia and dysequilibrium over 4 years. Examination revealed small amplitude nystagmus towards the right, impaired VOR to the left, palatal tremor, left-sided dysmetria, and an unsteady gait. MRI of the brain demonstrated increased T2/FLAIR signal within the inferior olive. Contrast enhanced and diffusion sequences were normal. MRA was normal. Electrocardiography, telemetry, and echocardiogram were normal. CSF was normal. Glial fibrillary acidic protein (GFAP) and vitamin E levels were normal. Genetic testing for hereditary forms of ataxia including spinocerebellar ataxia was not completed. Conclusion: Palatal tremor is commonly classified into symptomatic or essential subgroups. Symptomatic palatal tremor is frequently caused by a lesion in the triangle of Guillain and Mollaret leading to hypertrophic olivary degeneration. A subgroup of symptomatic palatal tremor form a syndrome of PAPT. Published details of cases of PAPT are sparse and the disorder appears to be mainly sporadic. Common features include progression of ataxia, olivary degeneration, gaze-evoked nystagmus, and internuclear ophthalmoplegia. There is no known effective treatment for progressive ataxia, which is the most disabling symptom of PAPT.

Objectives: The objectives of this study are to understand the impact of natalizumab on cognition beyond two years of therapy and to investigate whether baseline characteristics are predictive of clinical response. Methods: This is a single-center, 24-month, observational study. Sixty-three patients treated with natalizumab were assessed prior to monthly infusions using a Cogstate battery and the SDMT. A linear mixed model was conducted with duration of natalizumab therapy as a between-subjects factor (<=2 or >2 years), assessment as a within-subjects factor, and MSSS as a covariate. Results: There were no statistically significant differences between the key demographic variables aside for the MSSS (p=.0074). No patient showed evidence of sustained cognitive deterioration over the 24 month period. Irrespective of time on natalizumab, significant improvements were observed at the group level in executive function, verbal memory and working memory, whereas processing speed and attention remained unchanged. Impaired cognition or any other baseline parameter did not influence the trajectory of cognitive change over 24 months. Conclusion: Our results suggest that natalizumab preserves cognitive function, including the ability to learn, for 4 years and beyond of continuous therapy. This occurs irrespective of baseline characteristics.

Background: Risk of progressive multifocal leukoencephalopathy (PML), a serious adverse event of natalizumab therapy, is higher with positive anti-JC virus antibody status, greater cumulative exposure to natalizumab and prior immunosuppressant use. Plavina et al. (2014) showed that plasma or serum anti-JC virus antibody index value may allow further PML risk stratification. Among anti-JC virus antibody positive multiple sclerosis patients with no prior immunosuppressant treatment receiving natalizumab, anti-JC virus antibody index >6 months prior to PML diagnosis was significantly higher among those who developed PML with 96% consistently having an anti-JC virus antibody index >0.9. Methods: We describe a case of natalizumab-associated PML with low positive anti-JC virus index value prior to diagnosis. Results: A 53 year old man with 20 year history of relapsing remitting multiple sclerosis was diagnosed with PML following 46 infusions of natalizumab. Glatiramer acetate was his only prior immunomodulatory therapy. Routine MRI surveillance resulted in diagnosis of PML following detection of a confluent right anterior frontal T2 hyperintense lesion extending across the corpus callosum. Six months prior, routine MRI surveillance demonstrated a small right frontal T2 hyperintensity with no diffusion restriction while serum anti-JC virus antibody index was 0.69. Conclusions: Natalizumab-associated PML may develop despite low positive anti-JC virus index value.

Background: Multiple sclerosis (MS) exhibits a spectrum of clinical findings, especially in relapsing-remitting MS (RR-MS). To assess the effects of geographic location and ethnicity on RR-MS phenotype, we investigated RR-MS patients in Canada and Saudi Arabia. Methods: A retrospective cross-sectional analysis of patients receiving active care in MS Clinics was performed in Medina, Saudi Arabia and Edmonton, Alberta. Demographic and clinical data was collected for each patient. Results: 98 patients with treated RR-MS were recruited (n=51, Medina; n=47, Edmonton); 40 patients were Caucasian (Edmonton) while 46 patients were Bedouin (Medina). Although the disease duration was longer in the Edmonton (5.7+2.3 yr) compared to the Medina group (4.4+1.4 yr) (p<0.05), the mean age of RR-MS onset, relapse rate and EDSS change were similar. The female:male ratio was comparable in Edmonton (35:12) and Medina (32:19), as was the risk of optic neuritis. The likelihood of an infratentorial lesion-associated presentation differed (Edmonton, n=23; Medina; n=13) among groups (p<0.05). Spinal cord lesions on MRI were more frequent in Edmonton (n=18) compared to Medina (n=1) patients (p<0.05). Conclusions: Despite differences in location, ethnicity, and a predominance of infratentorial lesion burden the Edmonton group, the RR-MS phenotype displayed similar disease severity and trajectory in these cohorts.

Background: The beneficial effects of the injected disease-modifying drugs (DMDs) in relapsing-remitting Multiple Sclerosis have been previously reported. However the results related to disability outcomes and the reduction of disease progression in the pivotal trials and few longer studies are variable and inconclusive. Objectives: To determine the utilization and the disability outcomes of the DMDs on relapsing-remitting Multiple Sclerosis over fifteen years. Methods: A prospective open-label cohort of 262 clinical definite patients, 78 men and 184 women, with two attacks in the past two years and a disability level DSS≤5.5 were enrolled consecutively from December 1997 to November 1999. A descriptive analysis of the cohort and individual drugs outcomes were performed. The results were compared to natural history studies of Multiple Sclerosis as controls. Results: At 15 years, one-seventh, 38/262 (14.5%) remain on the initial prescription, Betaseron, 15/131 (11.5%), Copaxone, 16/102 (15.5%) and Rebif 7/28 (25%), Avonex 0/1. 223(63.6%) had discontinued at a mean duration of 5.5(SD=4.7) years. 95/262 (36.4%) remain on a drug after switches. The DSS levels of the individual DMDs were analyzed. Conclusion: One-seventh of participants remained on their first prescription. Because of low adherence, the impact of DMDs on disease progression in the longer term cannot be verified.

Objectives: To investigate if MS subjects treated with PRF 10mg BID will show a greater benefit from active enabled motor training compared with placebo. Methods: Single center, phase 4, pilot, placebo-controlled, double-blind 18 weeks study. Fifteen patients were randomized to receive PRF 10 mg BID and fifteen to received placebo BID. All patients participated in active enabled motor training of 3 sessions of 1 hour/week for 6 weeks. Patients were evaluated at -4, 0, 6 and 14 weeks using the timed 8 meters walk (8 MW), the 6 minute walk (6 MW) and the timed sit to stand (STS). Results: The PRF treated group achieved a higher mean percent improvement from baseline in all tasks at both 6 and 14 week time points. The difference reached statistical significance (mean difference of 14.29, p=0.046) for the 8MW at the 14 week time point. A higher incidence of responders (>20% improvement from baseline) was seen in the PRF treated group at 6 weeks on the 8MW (odds ratio [OR] of 2.31) and the 6MW (OR of 1.63), and at 14 weeks on the 8MW and the STS (OR of 2.0). Conclusions: PRF in MS patients appears to enhance the benefit of active enabled motor training and to better sustain it over the following 8 weeks.

Background: Donation after circulatory death (DCD) can reduce organ transplant waiting times. When defining death using circulatory criteria, brain function is usually not assessed. Residual brain function and the state of consciousness at the time of circulatory arrest is unknown. We have an ethical responsibility to ensure the donor is free of pain and psychological distress. Methods: We performed a scoping review of the literature to determine the time intervals associated with the loss brain function after circulatory arrest. Results: A total of 1133 articles were reviewed and 38 were included in the review. In humans, 8 studies showed loss of EEG activity under 30 seconds. Four studies revealed loss of EEG between 39.6 and 66 seconds. Clinically, loss of consciousness was shown to occur between 4 and 21 seconds. In animals, 13 studies also revealed loss of EEG under 30 seconds. In four other animal studies, EEG was lost between 37 and 120 seconds. Conclusion: The time required to lose brain function varied according to clinical context and method by which this function is measured. Existing literature is scarce and limited to observational studies and case reports.

Objective: Case report of NMDA receptor encephalitis in a young man with early refractory status epilepticus and atypical radiological findings. Background: Anti-NMDA receptor encephalitis is an autoimmune disorder due to antibodies to the NR1-NR2B heterodimer of NMDA receptor. On imaging, it typically presents with T2 hyperintensities in mesio-temporal lobes, cerebral cortex and basal ganglia. We present a case with a dramatic clinical evolution and novel imaging findings. Design/Methods: Case report and review of imaging. Results: 29-year-old male presented with mood disturbance followed by partial-complex seizures, facial dyskinesia and choreo-athetotic movements. Initial MRI showed subtle T2-hyperintensities in mesio-temporal lobes. Diagnosis of NMDA-receptor encephalitis was confirmed after CSF antibody detection. Prior to diagnostic confirmation, he developed refractory status epilepticus, and concomitant signs of herniation. A repeated MRI showed increased T2-hyperintensities of thalami and mesencephalon, with cerebellar involvement and transtentorial/foraminal herniation. Restricted diffusion was documented in the cerebellar cortex/thalami/putamina and caudate. IV corticosteroids and hypertonic fluid reversed herniation, and halted the seizures. Conclusions: To our knoweldge, we report the first case report of uncal and tonsillar herniation in NMDA-r encephalitis secondary to atypical, predominant cerebellar involvement. This case highlights life-threatening manifestation that physicians might encounter, and a possible role for high dose IV corticosteroids as an adjunct treatment for brain edema and seizures.

Background: IL-27 acts as a ‘master regulator’ in modulating inflammation and was responsible for a number of autoimmune diseases. However, the role of IL-27 was not addressed in Guillain-Barré syndrome (GBS). Methods: Sixty-five subjects including 19 with GBS, 7 with encephalitis or meningitis, 23 with multiple sclerosis or neuromyelitis optica as well as 11 with other non-inflammatory neurological disorders were enrolled. ELISA was used to detect the concentrations of IL-27 in paired samples of cerebrospinal fluid and plasma. Results: The mean concentration of IL-27 in GBS patients was significantly lower than in other neurological disorders both in CSF and in plasma (all p<0.05). GBS patients with cranial involvement, decreased reflexes, hypaesthesia, autonomic nerve dysfunction, MRC score <30 are inclined to have a lower CSF IL-27 level than patients without these symptoms (182 pg/ml, 181 pg/ml, 185 pg/ml, 185 pg/ml, 194 pg/ml vs 211 pg/ml, 205 pg/ml, 202 pg/ml, 198 pg/ml, 199 pg/ml, respectively). Similar results were noted in plasma except for cranial involvement. Conclusions: Production of IL-27 was disparate between GBS and other neurological diseases and a significantly lower level of IL-27 was observed in GBS patients, indicative of an anti-inflammatory role of IL-27 in GBS.

Background: Dysphagia from ALS may be treated by enteral nutrition; however criteria for timing of feeding tube placement has not been well studied. The aim of this project was to better understand the practice of enteral nutrition management within Canadian ALS clinics. Methods: ALS clinics were asked if they had written guidelines for timing of PEG insertion and if not, what criteria they use to make this decision. Results: Responses from 10 of 17 clinics were received. One clinic had written guidelines. Most used decline in respiratory function, dysphagia, weight loss or some combination of all three. Six clinics reported dropping FVC, ranging from 70% to 50% as prompting tube insertion. Five clinics reported weight loss as part of their criteria. Dysphagia was reported as the most important factor by 7 clinics. Psychological readiness for tube placement was a key factor in 3 clinics. Some clinics comment they place tubes in advance of dysphagia. Conclusion: Criteria for tube insertion varies between clinics. Practices generally reflect published recommendations, but vary on the emphasis of specific criteria. The lack of strong scientific evidence to guide decisions may contribute to management variability. Further study is needed to guide practice.

Background: In Charcot-Marie Tooth (CMT), vital components of either the myelin sheath or axon are abnormal, slowing nerve conduction and causing functional disability. Recently, there has been speculation the CMT may have an autoimmune component resulting from abnormal protein expression. Methods: Custom autoimmune neuropathy-focused microarray panels were printed in-house using antigens from Sigma, Abnova, Fitzgerald and Matreya according to Cambridge Life Science instructions. Antigens including Myelin Protein Zero, Peripheral Myelin Protein 22, and 20 other well-known gangliosides were tested for IgM and IgG antibodies. Students T-Test and Bonferroni correction factor were used to determine statistical significance between groups and in post-hoc subgroup analysis. Results: Plasma was tested from 17 patients with CMT and 25 young healthy individuals. CMT population consisted of 9 CMT-1a, 1 CMT-1b, 4 CMT-2a, 2 CMT-2f and 2 undetermined CMT type 2 patients. No ganglioside reached statistical significance under a Bonferroni Correction factor (p>0.01) nor were any gangliosides notably raised compared to normal. Sub-group analysis did not reveal theorized peak auto-antibodies levels depending upon their CMT sub-type compared to normal. Conclusions: Although previously shown to have increased auto-antibodies to myelin or axonal proteins, CMT individuals did not demonstrate increased autoantibody levels for the proteins tested at our centre.

Background: The response of Chronic Inflammatory Demyelinating Polyneuropathy ( CIDP ) to Intravenous Immunoglobulins (IVIG) treatment is well established. However, determination whether patients who do not respond to 2 IVIG treatments or those whose condition stabilizes (ICE Trial) would benefit from additional treatments remains unclear. We aim to identify time period required to reach maximal strength gains from IVIG treatment (plateau). Furthermore, we will assess nerve conduction studies (NCS) changes over time with IVIG treatment. This will help in establishing a time course for treatment of CIDP with IVIG to maximize recovery. Methods: We performed a retrospective chart review of 27 patients with CIDP, with diagnosis confirmed by European Federation of Neurological Societies/Peripheral Nerve Society Guidelines (EFNS/PNS). Each patient’s strength response including: grip strength, knee extension, elbow flexion and dorsiflexion (using JAMAR Dynamometer) and NCS changes over time during IVIG treatment were analyzed. The primary outcome is duration of IVIG treatment, in months, required to reach a plateau in strength. Secondary outcome is NCS change including: Terminal Latencies, Conduction Velocities, Compound Sensory and Motor action potentials in nerves of upper and lower extremities over treatment time (emerging trends). Results: Pending (available by April 2015) Conclusion: Pending (available by April 2015)

Aim/Background: We report a case of Acute Combined Central and Peripheral Demyelination (ACCPD). This rare disease presents with features of both peripheral and central demyelination. Methods: Case Report Results: A 24 year-old Iraqi female presented with acute onset of ascending paralysis, numbness and areflexia over the course of a few days. Systemic examination was negative. She responded to IVIG. She suffered two severe relapses over the next three months, which resolved rapidly with PLEX/corticosteroid. CSF was normal after first and second relapses. Brain and cord MRI revealed multiple T2/FLAIR hyperintensities consistent with multiple sclerosis. There were no longitudinally extensive cord lesions. Aquaporin 4 antibody assay is pending. ANA was strongly positive; anti-DSDNA and SS antibodies were negative; complement4 was low and serum cyroglobulins were positive. Hepatitis C was negative. Ganglioside antibody assay was negative. Anti-neurofascin is pending. Neurophysiology confirmed features of an acquired demyelinating neuropathy with profound secondary axonal denervation. Conclusions: The underlying etiology of ACCPD is presumed autoimmune likely secondary to auto-antibody targeting of central and peripheral myelin epitopes. Low complement component 4 and cryoglobulinemia in this patient supports an autoimmune pathogenesis. Neurofascin has been previously reported as one such auto-antibody in ACCPD.

Background: Our study examined whether there are differences in MS mortality rates across regions of Canada, which might suggest differences in environment or health care practice that influence outcome. Methods: Statistics Canada data on deaths due to MS and populations at risk, 1975-2009, were derived from the Research Data Centre, University of Alberta. Mortality rates and 95% confidence intervals (CIs) were calculated per 100,000 population for the Atlantic Provinces, Quebec, Ontario and Western Provinces (including Northwest Territories, Yukon, Nunavut), age-standardized to the 2006 population. Results: The average annual MS mortality rates for 1975-2009 per 100,000 population (CIs) were: Atlantic Provinces 1.09 (0.43,1.74); Quebec 1.30 (0.89,1.71); Ontario 1.08 (0.77,1.38); Western Provinces 1.39 (0.99,1.78). Female mortality rates were consistently higher than male rates but there were no differences in the female:male mortality rate ratios across regions. Trend analysis showed that rates were stable over the 35 year time span in 3 regions with non-significant average annual per cent increases/decreases of: Atlantic Provinces –0.43%; Quebec +0.12%; and Western Provinces +0.27%. Only Ontario showed a slight but significant increase of +0.81% (p<0.05). Conclusions: MS mortality rates are similar across the Canadian regions, suggesting that patients are not disadvantaged in terms of mortality by their place of residence.

Background: Charcot-Marie-Tooth (CMT) neuropathy is an increasingly polygenic disorder which limits clinical diagnoses due to phenotypic overlap resulting from the common final pathway of length-dependent axonal degeneration. The proband exhibited features of an axonal neuropathy manifesting upper and lower extremity distal amyotrophy, mild sensory loss, absent upper motor neuron findings, and mild hyperCKemia. Methods: Whole-exome sequencing (WES) was performed after failure to identify the familial variant with sequencing of multiple discrete CMT2 genes. Results: A novel VCP mutation (c.511A>C;p.Ser171Arg) was identified. This mutation segregated with an affected brother and father. All manifested a CMT2 phenotype with motor predominance. Further investigation of the proband revealed 1) a muscle biopsy with no inclusions or myopathic changes, 2) a skeletal survey negative for lucencies and hyerostoses, and 3) normal cognitive function. Conclusions: Mutations in valosin-containing protein (VCP) are associated with distinct neurologic phenotypes including 1) inclusion body myopathy, Paget disease, and frontotemporal dementia, 2) hereditary spastic paraplegia, and 3) amyotrophic lateral sclerosis. Recently, CMT2 has been described as a VCP-associated phenotype. This is the second report of a peripheral neuropathic phenotype resulting from a mutation in the VCP gene. The clinical presentation in this family suggests a unique clinical-biochemical phenotype consisting of motor-predominant CMT2 with mild hyperCKemia.

Background: Standardized order sets are thought to improve patient outcomes in multiple ways. They reduce costs without reducing quality of care, and improve efficiency. In both surgical and medical conditions patients benefit from order sets in various disease states. In Guillain-Barre syndrome (GBS), the use of standardized order sets may be beneficial as there are a defined set of disease-specific diagnostic tests and treatments to be implemented. Here, the primary aim was to search for, and evaluate standardized order sets for GBS, and to provide a basis for development of future pathways. Methods: We used the Cochrane, TRIP, and MEDLINE/PUBMED databases, searching between January 1966 and April 2014. Search terms included: “Guillain-Barre Syndrome” and its synonyms, “(standardized) order set”, “clinical pathway”, “neurology” and “admission bundle.” Results: Despite anecdotal evidence of order sets, no formal data has been published showing benefit after implementation of these sets in GBS or any neurological condition. Conclusions: Although evidence exists for use of standardized order sets in surgical and medical settings, no published data exist in neurology. Given GBS has a defined set of disease-specific and state-specific treatment options, a standardized order set used on admission for GBS patients may prove to be beneficial.

Background: Progressive encephalomyelitis, rigidity, and myoclonus (PERM) is a variant stiff-person plus syndrome consisting of brainstem and pyrimidal dysfunction, muscular rigidity, stimulus-evoked spasms, and dysautonomia. Continuous motor-unit activity from ectopic anterior horn cell discharges underlies the myotomal hyperactivity. Case Report: A 51-year-old man with an 8-year history of “spasmodic” mid and low back pain presented with increasing stiffness, hyperekplexia-induced opisthotonus-like posturing, urinary retention, long-tract motor signs, and diplopia. He had a recent history of biopsy-confirmed leucocytoclastic vasculitis-associated diffuse maculopapular rash. He responded well to IVIg treatment manifested by improved 1) gait fluidity, 2) bowel and bladder function 3) tolerance to startle, and 4) vision. Results: Serological testing revealed positive anti-glycine receptor antibodies. Anti-glutamic acid decarboxylase and voltage-gated K+-channel antibodies were absent. A chest CT was unremarkable. Conclusions: This is the second case of seropositive PERM in Canada and the first associated with leucocytoclastic vasculitis. Pathologic findings in PERM reveal perivascular lymphocytic cuffing in the rhombencephalon and spinal cord. Glycine receptor localization correlates with neurologic dysfunction. Mid-brain involvement may underlie the autonomic dysfunction but evidence of direct glycinergic inhibition of the external urethral sphincter in Onuf’s nucleus may be responsible for urinary retention.

Background: Cerebral artery stenosis is an important risk factor for ischemic strokes. This study aims to explore intracranial and extracranial artery stenosis in a large northeast Chinese cohort. Methods: We recruited 14793 outpatients and hospitalized patients to identify cerebral artery stenosis. Artery stenosis screening was done with transcranial Doppler (TCD) for intracranial arteries and carotid duplex sonography for extracranial arteries. Results: More intracranial than extracranial artery stenoses were identified (4255 versus 2809, i.e. 28.8% versus 19.0%, P<0.05). Similarly, mere intracranial stenosis was significantly more common than extracranial artery stenosis in this population (2632 versus 1186, i.e. 17.8% versus 8%, P<0.05). Among all identified intracranial arteries stenoses, the proportion of middle cerebral artery (MCA) stenosis was the highest. More intracranial than extracranial artery stenoses was seen within each age group, and rates of both increased with age. Intracranial and extracranial artery stenosis was more frequently identified in males than females. Conclusions: Incidence of cerebral artery stenosis in the population increases with age. Intracranial artery stenosis is more common than extracranial artery stenosis and the MCA stenosis accounted for the highest proportion, within each age group. More males suffer from intracranial or extracranial artery stenosis than females.

Background: Assessment of ischemic penumbra during the acute stage of cerebral infarction is crucial for a decision to initiate thrombolytic therapy and for predicting stroke evolution. Although controversial as a perfect equivalence to penumbra, perfusion weighted imaging (PWI)-diffusion weighted imaging (DWI) mismatch may predict the response to thrombolysis. Due to the reliance on contrast agents in PWI, noninvasive alternatives remain an unmet need. Methods: We herein investigate the potentials of SWI as an alternative to PWI in defining ischemic penumbra and in predicting stroke outcome. A multimodal magnetic resonance imaging work-up which includes conventional magnetic resonance imaging sequences (T1WI, T2WI and FLAIR), DWI, PWI and SWI was performed. The Alberta Stroke Programme Early CT Score (ASPECTS) was used to evaluate the changes in DWI, SWI and PWI. Results: The mismatch of SWI-DWI was comparable with that of PWI-DWI (p>0.05). Furthermore, the grade of prominent vein and the cerebral blood volume in the ipsilateral brain tissue were positively correlated. Conclusions: SWI can be used as a noninvasive alternative to identify occlusive arteries and to evaluate the ischemic penumbra. The susceptibility vein sign may represent thrombosis in arteries whereby being helpful to identify responsible blood vessels in ischemic stroke.

Introduction: It has been recognized in the past few decades that different ethnic groups living in Canada may have different stroke epidemiology. This presentation is focused on the stroke patterns of Chinese-Canadians living in the Toronto area. Methods: Two retrospective case-controlled studies were carried out between 1990- 2000 to study the stroke characteristics of Chinese-Canadians living in Toronto. Statistical analysis was carried out by the Institute of Clinical Evaluative Sciences. A further retrospective study was also carried out in 2011 to look at the relationship between stroke and diabetes mellitus amongst this population. Results: Chinese-Canadians were found to have 1/6 the prevalence of extracranial vascular stenosis. They have a higher frequency of intracranial vascular disease which may be due to the higher frequency of hypertension and diabetes mellitus. Higher incidence of intracranial hemorrhage was found compared to Caucasian controls which may be due to the lack of awareness and optimal treatment of their hypertension. Details of the results of these three studies will be presented. Conclusions: This is the first long term retrospective study of the stroke patterns and epidemiology for Chinese-Canadians residing in Toronto. Further prospective population-based study will be vital to study the important interactions between genetics and environment in the pathogenesis of different strokes for different folks.