Background: Morvan syndrome is an autoimmune paraneoplastic disorder affecting of voltage-gated potassium channels, most commonly the CASPR-2 subunit. The disorder is primarily characterized by hyperexcitability of both the central and peripheral nervous system accompanied by autonomic dysfunction. Clinically, the syndrome manifests as confusion, hallucinations, insomnia, hyperhidrosis, orthostatic hypotension, and muscle cramps with myoclonus. Methods: Patient chart, imaging, electrophysiology, and laboratory findings were reviewed from the time of MS diagnosis and through the course of treatment until symptom resolution. Results: Here we report a case of Morvan Syndrome in a 56 year old male with a previous history of thymic squamous carcinoma accompanied by paraneoplastic myasthenia gravis and myositis. His clinical presentation was notable for subacute onset of muscle cramping, insomnia, which progressed to also include visual and auditory hallucinations. He also had notable dysautonomic symptoms including orthostatic blood pressure changes, sialorrhea, and hyperhidrosis. The diagnosis was confirmed with a positive serum assay for antibodies against the CASPR-2 subunit of voltage-gated potassium channels. Conclusions: This case is notable because to our knowledge it one of the first to document a voltage-gated channelopathy in association with previous thymic cancer (and not thymoma). Moreover, this is a patient presenting with two other other autoimmune syndromes, i.e. myasthenia gravis and myositis.

Background: While anti-Hu antibody associated encephalitis has been well-documented in association with a variety of neoplastic processes, paraneoplastic limbic encephalitis and sensory ganglionopathy with positive anti-Hu antibodies has not previously been linked in the literature with a neuroendocrine gastric tumour of advanced stage. Methods: Case report Results: We present the case of an 86-year old woman who developed behavioural changes, paroxysmal anxiety attacks and poor balance several months after being diagnosed with poorly differentiated gastric small cell tumour in a clinical setting of weight loss and anemia. Anti-Hu antibodies were present. MRI showed signal abnormalities in the right mesial temporal lobe with contrast enhancement. Paroxysmal lateralized EEG changes were recorded and EMG/NCS showed absent sensory nerve responses. Behavioural symptoms stabilized under treatment with intravenous immunoglobulins, but sensory ataxia continued to worsen. The patient declined further therapy and deceased two months after transfer to palliative care. Conclusions: To our knowledge, this is the first report linking small cell gastric tumour with limbic encephalitis, sensory ganglionopathy-associated ataxia and anti-Hu antibodies. This description further broadens the clinical spectrum of anti-Hu syndrome.

Background: Clinicians rely on a correction formula (Predicted CSFWBC=CSFRBC×BloodWBC/ BloodRBC) to determine if a true CSF leukocytosis exists. This formula may overestimate true CSF leukocytosis leading to delayed diagnosis and treatment of meningitis. Methods: A retrospective review of CSF data of 105 patients registered at 3 hospitals (Saskatoon, Canada) between 2011-2013 who met the following criteria: 1) CSF samples from lumbar puncture (LP) contained≥1000 RBC/mm3; 2) a complete blood count (CBC) performed within 24 hours of LP; and 3) CSF not obtained due to high clinical suspicion of meningitis and was negative for microbial staining and culture. Regression analysis was performed to determine the relationship between actual and predicted CSF WBC values. Results: Mean adult age was 48.9 years; CSF profile (mean WBC 146.3×106/L; RBC 17374×106/L; glucose 4.1 mmol/L; protein 1.4 g/L); mean peripheral WBC 8.2×109/L; RBC 3.9×109/L. Mean pediatric age was 1.4 years; CSF profile (mean WBC 171.8; RBC 41763; glucose 2.7; protein 1.7); mean peripheral WBC 12; RBC 7.2. The observed LP CSF WBC value was 47% of predicted (r2=0.54 pediatric cohort; r2=0.91 adult cohort). Conclusions: True CSF leukocytosis in both pediatric and adult patients could be missed in a traumatic CSF sample if correction is based on current formulas. We propose a modifcation: ObservedCSFWBC=0.5×[CSFRBC×BloodWBC/BloodRBC].

Background: Cognitive impairment is highly prevalent in individuals with end stage kidney disease (ESKD) undergoing hemodialysis. The cause is not understood. Our overall hypothesis is that repetitive cerebral hypoperfusion during hemodialysis contributes to accelerated cognitive dysfunction in this patient population. Methods: All participants underwent a baseline assessment with the KINARM, a robotic device that provides quantitative metrics of the sensorimotor control of the upper limb in humans. For patients undergoing hemodialysis, BtO2 was monitored during one dialysis session per week. Follow up KINARM assessment was done at 3 months. Results: To date, 7 patients have completed baseline testing, with 3 being re-evaluated at 3 months. At baseline, patients were impaired on of the 8 tasks, with the exception of a test of working memory. There was a variable correlation between hemodynamics (e.g. blood pressure and heart rate), fluid removal, and BtO2 levels. At 3 months, the 3 patients improved on the majority of the performance metrics assessed with the KINARM. Conclusions: The KINARM is a feasible instrument to measure cognitive dysfunction in individuals with ESKD. In a small cohort, there is improvement in neurocognitive function 3 months after the initiation of dialysis.

Background: Depression and pain are significant clinical problems that are comorbid with Parkinson’s disease (PD). However, the relationship of these variables with the marital status of patients with PD has not been explored in previous studies. The goal of this study was to assess the possible relationship between depression prevalence, depression severity, and pain interference with the marital status of the sufferers of PD. Methods: This study included 40 patients and 40 healthy control participants who were assessed for depression prevalence and pain interference using The Hospital Anxiety and Depression Scale and the Brief Pain Inventory, respectively. Results: When compared to the control groups, the PD (Single) group was found to have the highest prevalence of depression, followed by the PD (Married) group whereas the Control (Single) group was found to have a higher prevalence than the Control (Married) group (P<0.0001). A main effect was found on depression severity (P<0.0001), but no significant differences were observed between the PD groups. Lastly, PD (Single) patients had significantly greater pain interference scores than the PD (Married) patients (P<0.05) with no other significant case-control or control-control group differences. Conclusions: Patient-spouse relationship may have a mitigating effect on patient outcomes of depression prevalence and pain interference.

Background: Pain is a disabling non-motor symptom of Parkinson’s disease (PD), which remains underacknowledged, undertreated and often undeclared by patients in the clinical practice. Prevalence of pain ranges from 40-75% among PD patients; however, clinical determinants and self-reported perceptual experiences of pain require further research. Methods: 121 PD patients (age: 67.3±11.4) from community-based clinic were analyzed cross-sectionally. Perceptual experiences and clinical predictors of pain were assessed using structured interviews, questionnaires and neurological examinations. Results: 80 (66%) PD patients reported pain; 65 (54%) described the severity as ‘moderate/high’. Dystonic was the most frequent clinical pain 37/80 (48%), followed by neuropathic (36%), akathisia (29%) and musculoskeletal (28%). More than one type of clinical pain was assessed in 22 (28%) patients. Aching was the most common perceptual descriptor of pain (46%), followed by sharp/deep (30%), tension (18%) and dull (14%). PD localized on the right side quadrupled the odds of pain on the right (OR=4.4, 95%CI [1.1-18.2]); and pain described as ‘sharp’ predicted neuropathic pain (OR=5.6, 95%CI [1.1-29.2]). Pain prevalence also increased with progressive Hoehn-and-Yahr stage. Interestingly, only 51% of patients perceived effects of PD medications on pain symptomology. Conclusions: Perceptual descriptors of pain can provide novel approaches to classify, treat and manage PD. Longitudinal investigations with larger sample are warranted.

Background: Health-related quality of life (HRQoL) data is valuable, but limited. This analysis describes the impact of onabotulinumtoxinA treatment on HRQoL and level of treatment satisfaction in cervical dystonia (CD) patients. Methods: A multicenter, prospective, observational study in CD patients initiating onabotulinumtoxinA treatment (NCT01655862); ≤8 treatments administered at the physician’s discretion. Primary measures (baseline, 4/8 weeks post-treatment, and before final treatment): pain numeric rating scale (PNRS) and cervical dystonia impact profile questionnaire (CDIP-58). Secondary measures (8 weeks post-treatment): patient/physician treatment satisfaction. Results: 61 patients (31.3-86.3 years old) were enrolled (efficacy cohort); majority had moderately severe CD (77.0%) and were female (77%). CDIP-58 domain and PNRS scores decreased from baseline, with significant changes (p<.0001) by 4 weeks post-treatment 3 (mean±SD): symptoms (-18.8±16.1), daily activities (-7.2±13.7), psychosocial sequelae (-17.4±13.4), and PNRS (-1.8±3.3). Most patients (78.0% and 94.4%) felt their condition was improved and majority of physicians (68.9% and 75.0%) indicated satisfaction with patients’ responses following treatments 1 and 2, respectively. 27 patients reported 56 treatment-related adverse events (52 resolved, 4 ongoing); none were serious. Conclusions: No new safety signals were identified. Patients and physicians appear to be satisfied with onabotulinumtoxinA treatment for CD. Results suggest that onabotulinumtoxinA treatment may help improve HRQoL.

Background: Restless leg syndrome (RLS) is common with musculoskeletal pain conditions and has been associated with small fiber neuropathy. There are few reports of non pharmacological management of RLS. The purpose of this paper was to report the use nerve mobilization exercises in a group of patients with primary RLS with and without co-morbid chronic non specific low back pain (LBP). Methods: 26 consecutive patients (11M/14F) with primary RLS and LBP attended a mean of 12 physiotherapy sessions (range 4-16). Patients were given 3 neural mobilization exercises to do twice daily 15-20 repetitions. Outcome measures were: Global Rating of Change Scale (GROC); Restless Legs Syndrome Rating Scale (RLS-RS); and RLS Ordinal Scale (RLS-OS). Based on the RLS-RS 1 was very severe, 8 were severe and 17 were moderate. Results: Follow up was a mean of 14 months (range12-16). Mean baseline for the RLS-RS was 22.8. The mean change was 20.3 (range 14-26). The mean baseline for the RLS-OS was 4.3. The mean score at follow up was 1.2 (range 1-4). GROC changed a mean of 6.2 (range 3-7). Conclusions: The results suggest that targeted exercises may be useful in managing primary RLS. A level 1 clinical trial is warranted. Further research is needed to identify the mechanism of action.

Background: D2 receptor antagonists have been a mainstay in treating schizophrenia. Dopamine agonists used in the treatment of Parkinsonism can aggravate psychosis. Dopaminergic drugs with emphasis on other receptor subtypes with less D2 activation could reduce Parkinsonism in schizophrenic patients without seriously aggravating Parkinsonism. Rotigitine acts primarily on D3 receptors, while activity on other dopamine receptors is 8-20 times less. We report the successful treatment of a schizophenic patient with rotigitine and contend that its effectiveness relates to rotigitine’s receptor profile. Methods: Single case study with follow-up. Results: A 67 year old woman with longstanding schizophrenia developed severe, progressive Parkinsonian features over 2 years despite stable antipsychotic therapy. More than one tablet of levodopa-carbidopa 100/25 precipitated psychosis. Risperidone was changed to cloazapine without benefit in Parkinsonism. The rotigitine patch was introduced and increased to 8 mg/24 hours without aggravating her mental status and produced considerable improvement in Parkinsonian features. Conclusions: Rotigitine is worth exploring as a treatment for severe Parkinsonism in patients with schizophrenia.

Background: Longitudinally extensive transverse myelitis (LETM) is a demyelinating condition that is associated with diseases such as neuromyelitis optica spectrum disorder (NMOSD), acute disseminated encephalomyelitis, collagen vascular disease, or can be idiopathic. LETM can be severe enough to cause quadraparesis, marked sensory dysfunction, and respiratory failure. Rarely, these patients are unresponsive to conventional immune therapy. Methods: We report two cases of severe LETM with acute development of quadraparesis and respiratory failure requiring intensive care admission and failure to respond to high-dose corticosteroids, plasma exchange, IVIg and rituximab. Disease cessation and ultimately, significant recovery, was achieved after an 8-day cyclophosphamide induction. Results: A 21 yo female with antibody positive NMOSD and a 19 yo male with idiopathic LETM remained quadraparetic and ventilator dependent with active MRIs despite multiple courses of intravenous methylprednisolone, plasma exchanges, and in the NMOSD patient, IVIg and a 4-week course of rituximab. Both patients ultimately improved significantly and are now ambulatory with subsequent cyclophosphamide induction. Conclusions: In patients with severe LETM of presumed immune origin, who fail to respond to corticosteroids and plasma exchange, cyclophosphamide induction should be considered. This agent provides a more robust immunosuppressive response and can be induced rapidly. Cyclophosphamide effects and supportive evidence are further discussed.

Background: Recently, many cases of autoimmune encephalitis with positive GAD65 (Glutamic acid decarboxylase) antibodies have been described in the literature. However, it remains an understudied topic. Methods: We conducted a search on reported cases of anti-GAD65 encephalitis. Specific variables were identified as general characteristics, clinical manifestations, MRI and EEG findings, concomitant systemic autoimmune disorders and cancer, and outcome and autoantibodies findings. Results: We identified a total of 58 cases, from one to 70 years old. It most frequently presented with seizures (97%) and memory impairment (59%). It commonly occurred in association with systemic autoimmune disease, particularly diabetes (28%). Brain MRI was usually abnormal (78%); involvement of temporal lobes was more frequent than multifocal abnormalities (59% vs 16%). GAD65 antibodies were reported positive in CSF and/or serum (31% in serum only). Other antibodies such as GABABR, GABAAR and VGKC were concurrently reported positive in some cases (19%). However, we found that the vast majority of cases were not tested for all those cell-surface antibodies. Overall, no distinctive pattern of clinical and paraclinical findings was found. Persistent impairments were common. Optimal treatment remained undefined. Conclusions: Prospective studies recruiting patients with autoimmune encephalitis are needed to better elucidate the contributions of GAD65 autoantibodies, and to evaluate treatment and outcomes in this population.

Background: Disease-modifying therapies (DMT) have been shown to reduce relapses and delay disability in individuals with relapsing-remitting multiple sclerosis (MS). However, these medications can cause adverse events (AE) leading to poor adherence. To better understand their clinical utility, this study examined real-life experiences with DMT in a tertiary MS clinic. Methods: A retrospective chart review (1999-2015) was conducted to evaluate the prevalence of AE and discontinuation rates of Health Canada approved DMT. Results: 445 MS patients who have used at least one DMT in their lifetime were reviewed. Among first-line injectable therapies, interferon beta (IFNβ) 1-α IM users (49.6%) were most likely to report an AE. Flu-like reactions and injection site reactions were the most commonly reported AE. Among first-line oral therapies, BG-12 users (58.5%) were most likely to report an AE. The most common AE were flushing and gastrointestinal upset. DMT that were most frequently discontinued as a result of AE were IFNβ 1-α SC (39.3%), IFNβ 1-α IM (36.8%) and BG-12 (34.6%). Conclusions: The prevalence of AE and discontinuation rate were congruent. In comparison with recent literature, this study demonstrated lower prevalence of AE but equivocal or higher discontinuation rates. This discrepancy could represent a more realistic depiction of the impact that DMT AE have on patients.

Background: Adrenoleukodystrophy (ALD) is a peroxisomal disorder that leads to the accumulation of very long chain fatty acids in the body. Younger males typically present with a catastrophic cerebral demyelinating disease, while adult males tend to develop a progressive myelopathy and neuropathy. Methods: Case presentations and literature review. Results:Case1: A 58-year-old male with a three-year history of unsteady gait. His MRI showed multiple T2-hyperintensities most prominently in the posterior corpus collosum (which progressed over time) as well as spinal cord atrophy. Primary progressive multiple sclerosis (PPMS) was suspected. Case 2: The patient’s bother, a 49-year-old, had a ten-year history of difficulty walking. MRI findings included a single large T2 hyper-intensity spanning the anterior aspect of the corpus collosum and an atrophic spinal cord. Given the family history, both brothers were investigated for and diagnosed with ALD. Conclusions: Both cases are of males presenting with a progressive myelopathy in middle age. In the first case, the history, physical exam, and imaging findings were most consistent with PPMS. However, the second case was less typical for MS prompting further investigations. These cases highlight the need to have a broad differential when confronted with atypical cases of MS and reminds the clinician of the phenotypic variability of ADL.

Background: Cognitive dysfunction following coronary artery bypass surgery is a regular occurrence, but its cause is still unknown. In order to devise strategies to mitigate this acquired disability, a precise and quantitative description of the post-operative neurocognitive phenotype is necessary. This study is designed to assess the feasibility of using the KINARM robot to quantify the changes in the neurological function after cardaic surgery. Methods: Patients without prior history of cognitive dysfunction were recruited from the pre-operative cardiac surgery clinic, and underwent pre-operative assessment with the KINARM. The KINARM provides a quantitative assessment of the neurocognitive control of the upper limbs. During bypass surgery, brain tissue oxygen levels were measured with near-infrared spectroscopy. Patients were reassessed with the KINARM post-operatively at 3 months. Results: To date, 12 participants have been recruited (mean age = 65 years, all male). On straightforward tasks, such as visually guided reaching, the majority of patients scored within the normal range, both pre- and post-operatively. In more complex tasks, required visuospatial and executive functioning, post-operative deficits were more pronounced. Conclusions: It is feasible to use the KINARM robot to provide a quantitative measurement of the neurocognitive phenotype of patients after cardiac surgery.

Background: Facial diplegia with parasthesia (FDP) is a rare variant of Guillain–Barre syndrome (GBS), and has been reported in less than 1% of GBS cohorts. Here we describe a case of FDP with novel imaging findings and discuss the differential diagnosis. Methods: Case: A 39-year-old man referred to the emergency department with a 2 week history of right facial palsy progressed to bilateral facial palsy. His exam demonstrated severe, complete facial diplegia with only very mild limb weakness and present but diminished deep tendon reflexes. Results: Cerebrospinal fluid analysis showed albuminocytologic dissociation. Electromyography was consistent with a demyelinating process. MRI with contrast revealed bilateral enhancement of the facial nerves in the intracanalicular portion and in the region of the geniculate ganglion. A diagnosis of GBS was made and the patient was treated with IVIG. Over the course of several weeks the patient improved. Conclusions: Although nerve root enhancement of the spinal cord is described with GBS, nerve root enhancement effecting cranial nerves has only rarely been described. In addition, the relative limb-sparing with complete facial paralysis in this case is also an unusual phenotype. The Gadolinium enhancement of the bilateral facial nerves is thought to represent blood brain barrier breakdown due to GBS.

Background: Myotonic dystrophy is an autosomal dominant condition affecting distal hand strength, energy and cognition. There is a neuromuscular patient portal under development that has the potential to give voices and resource access to patients, regardless of location via the internet and social media. The current state of access to technology and underlying factors affecting use and interest were explored. Methods: Surveys were mailed to 156 participants with myotonic dystrophy type 1 (DM1) through the Canadian Neuromuscular Disease Registry. The survey questions touched on demographics, technology use, internet use, and interest in the portal. Results: Seventy-two participants (43 female) responded so far and 50% were younger than 46 years. Most (62/72) used the internet and 94% of participants had access to an internet-connected device. Almost half of the responders (34/72) used social media. The complexity and cost of technology were commonly cited reasons not to use technology. The majority of responders (79%) were interested in a myotonic dystrophy patient portal. Conclusions: DM1 patients have access to and use technology such as computers and mobile phones. They expressed interest in a portal that would provide them with access to relevant information such as guidelines, self-management modules, educational videos, and support groups.

Background: The distal hereditary motor neuropathies (dHMN) have been characterized through case reports and family studies. Their genetic characterization remains a work in progress. An appreciation of the genetic underpinnings may lead to treatment options in the future. Hence reports, like this one, which add to this understanding, remain extremely important. Methods: The clinical presentations, electrophysiology and genetics of two patients with the dHMN I phenotype are described. Results: A mother and son presented with slowly progressive distal weakness of the lower extremities with onset in the first and second decades. Distal weakness of the upper extremities developed later. Examination 20 and 50 years after onset revealed wasting and weakness of distal upper and lower extremity muscles with absent distal and preserved proximal deep tendon reflexes. Sensory examination was normal. Electrodiagnostic studies demonstrated a motor axonopathy. Genetics testing revealed a missense mutation on chromosome 7, exon 11 of the GARS gene: c.1415A>G (p.His472Arg). Conclusions: GARS mutations have been identified in patients with the dHMN I (juvenile onset distal weakness and wasting) and dHMN V (upper limb predominant) phenotypes. However, this mutation has not previously been directly linked to the dHMN I phenotype.

Background: Length-Dependent Sensorimotor Peripheral Neuropathy (LDSMPN) affects the longest nerve fibers in the body. Less well-appreciated, and absent from the current literature, is that LDSMPN affecting thoracic segments gives rise to ventral abdominal sensory loss on clinical exam. Methods: Consecutive patients seen for LDSMPN (n=30) were evaluated prospectively for the presence or absence of ventral abdominal sensory loss. Demographic variables, symptoms, quantitative neurologic findings (Neuropathy Impairment Score [NIS]) and final diagnosis were examined using descriptive statistics. Results: Ventral abdominal sensory loss was documented in 20/30 LDSMPN patients (66.7%), mean age was 64.1 years (range 33-81), M:F gender ratio was 19:11, mean NIS was 21.4 (range 0-77). NCS/EMG abnormalities were found in 25/30 patients, with 5/30 having a clinical exam and/or other electrophysiological evidence convincing for LDSMPN. LDSMPN patients without ventral abdominal sensory loss (n=10) had a mean age of 61.2 (range 45-73), M:F of 7:3, and mean NIS of 20.9 (range 0-54). Conclusions: 1) Ventral abdominal sensory loss appears to be common in patients diagnosed with LDSMPN of a variety of causes; 2) in addition to those innervating distal limb territories, distal sensory fibers from the thoracic region represent another category of length dependent involvement in LDSMPN; 3) the clinical examination of LDSMPN should include the ventral abdomen.

Background: Mononeuritis multiplex is a painful, asymmetrical peripheral neuropathy involving motor and sensory nerves. This neurological condition is classically associated with systemic diseases such as connective tissue disorders, vasculitis, hematologic diseases including cryoglobulinaemia and amyloidosis. It has also been reported infrequently as a paraneoplastic or post infectious disorder. Methods: Case report Results: We are reporting a case of a 35-year-old man who presented with mononeuritis multiplex following an infectious mononucleosis associated with a mixed cryoglobulinemia. He was treated with IVIG, IV pulse steroid and a prednisone taper over 7 months. Later on, he had a nerve transfer from FCR (flexor carpi radialis) to ECRB (extensor carpi radialis brevis) and PIN (posterior interosseous nerve) due to complete denervation of the PIN without evidence of spontaneous recovery. Conclusions: Acute EBV infection should be suspected in the setting of mononeuritis multiplex. This is the first reported case of nerve transfer for this type of nerve injury.

Background: Effects of stroke at the cellular and sub-cellular level remain poorly understood by conventional techniques. We use synchrotron-based imaging techniques to study elemental and biochemical changes in the infarct and penumbra after stroke in an experimental model. Methods: Ischemic stroke is induced in mice using the previously validated photothrombotic model. Animals are sacrificed at various time-points after stroke. Fourier transform infrared spectroscopic imaging (FTIRI) is used to gather sub-cellular (<1 µm spatial resolution) imaging data of lipid oxidation and protein aggregation in the areas of interest. X-ray fluorescence (XRF) imaging is used to image the distribution of bio-important elements at the cellular and sub-cellular spatial resolutions. Routine histology and immunohistochemistry are used to co-localize cell-types to areas of interest. Results: Preliminary XRF results indicate significant reduction in the concentration of multiple elements in the infarct, compared to the penumbra, at day 1 post-stroke. Some elements begin to return to normal concentration in the penumbra at day 3. FTIRI data shows that lipid and total protein levels decrease, while aggregate protein levels increase in the penumbra. Conclusions: Multi-modality synchrotron imaging can be used to map elements as well as bio-molecules in a stroke model. A better understanding of these changes can guide therapeutic interventions after stroke.