The purpose of this review is to provide an update of the research regarding the etiology, diagnosis and management of psychogenic non-epileptic seizures (PNES). A literature search using Pubmed, Ovid MEDLINE and EMBASE database was performed from 2000 up to August 2017. We have evaluated the different factors leading to PNES as well as the diagnostic approach and management of this disorder which continue to be very difficult. The coexistence of epilepsy and PNES poses special challenges and requires the coordinated efforts of the family physicians, psychiatrists, psychologists and neurologists. Although this condition has an overall poor prognosis, a multidisciplinary approach in the diagnosis and management of this disorder would likely improve the outcomes. We have proposed a diagnostic and treatment algorithm for PNES and suggested a national registry of patients suffering from this condition. The registry would contain data regarding treatment and outcomes to aid in the understanding of this entity.

Background: Neurolymphomatosis is a process of neoplastic endoneurial invasion, most strongly associated with non-Hodgkin’s lymphoma. It must be distinguished from paraneoplastic, metabolic, nutritional and treatment-related causes of neuropathy that are common in this patient population. Methods: This brief case series illustrates the protean manifestations of neurolymphomatosis of the brachial plexus, ranging from focal distal mononeuropathy to multifocal brachial plexopathy, either as the index manifestation of lymphoma or as a complication of relapsing disease. Results: Prominent asymmetry, pain and nodular involvement on neuroimaging may help distinguish neurolymphomatosis from paraneoplastic immune demyelinating radiculoneuropathy. MR neurography criteria for the diagnosis of neurolymphomatosis include hyperintensity on T2 and STIR sequences, focal and diffuse nerve enlargement with fascicular disorganization and gadolinium enhancement. No specific anatomical distribution within the brachial plexus has, however, been found to be characteristic. Fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging is the imaging modality with the highest sensitivity for detection of nodal or extranodal spread in lymphoma. Conclusions: Brachial plexus neuropathy in neurolymphomatosis is highly protean in its distribution, semiology and relation to lymphoma staging. Dedicated MRI and PET-CT imaging are leading diagnostic modalities.

Objective: To define the prevalence of psychiatric symptoms of anxiety and depression in patients at the time of their first seizure presentation to a neurologist. Methods: Our pilot study uses a cohort approach with multimodal data (clinical, social, structural [3T magnetic resonance imaging], and functional [electroencephalogram]). We screened 105 patients referred to the Halifax First Seizure Clinic between 2014 and 2016 and 51 controls. All participants completed two screening questionnaires: Neurological Disorders Depression Inventory for Epilepsy and Generalized Anxiety Disorder 7-Item. After applying the exclusion criteria, the study population consisted of 57 patients with unprovoked first seizure and 31 controls. The prevalence of anxiety and depression was based on cutoff scores of >15 and >14 respectively. Results: Unprovoked first seizure patients showed higher prevalence of depression (33%) compared with control (6%) with an odds ratio (OR) of 2.75 (95% confidence interval [CI], 0.72-10.5). There was no significant difference in the prevalence of anxiety between control subjects (9.7%) and unprovoked first seizure patients (23%). Subcategory analysis conducted after diagnosis confirmation revealed significantly increased OR of depression in patients diagnosed with new-onset epilepsy (OR, 11.6; 95% CI, 2.1-64.0) and newly diagnosed epilepsy (OR, 20.0; 95% CI,2.2-181), but not first seizure only patients (OR, 2.2; 95% CI,0.28-17.6) compared with control. Conclusions: Our study supports a bidirectional relationship between the first seizure and depression. Prevalence rate of depression increased with duration of undiagnosed epilepsy at the time of first clinical assessment.

Objective: Neuronal ceroid-lipofuscinoses are a heterogeneous group of inherited disorders in which abnormal lipopigments form lysosomal inclusion bodies in neurons. Kufs disease is rare, and clinical symptoms include seizures, progressive cognitive impairment, and myoclonus. Most cases of Kufs disease are autosomal recessive; however, there have been a few case reports of an autosomal dominant form linked to mutations within the DNAJC5 gene. Methods: We describe a family with Kufs disease in which the proband and three of her four children presented with cognitive impairment, seizures, and myoclonus. Results: Genetic testing of all four children was positive for a c.346_348delCTC(p.L116del) mutation in the DNAJC5 gene. The proband brain had an abundance of neuronal lipofuscin in the cerebral cortex, striatum, amygdala, hippocampus, substantia nigra, and cerebellum. There were no amyloid plaques or neurofibrillary tangles. Immunohistochemistry demonstrated that the cholinergic neurons and cholinergic projection fibers were spared, but there was a profound loss of choline acetyltransferase within the caudate, putamen, and basal forebrain. This suggests a loss of choline acetyltransferase as opposed to a loss of the neurons. Conclusions: This report describes the clinical history of autosomal dominant Kufs disease, the genetic mutation within the DNAJC5 gene, and the neuropathological findings demonstrating depletion of choline acetyltransferase in the brain.

Introduction: In an effort to better understand why cognitively normal patients were referred to a memory clinic, we sought to identify features of “worried well” patients to better identify those more likely to be cognitively normal. Methods: In total, 375 consecutive patients referred by primary care practitioners to a Rural and Remote Memory Clinic were categorized into two groups based on their neurologic diagnosis, “worried well” (cognitively normal, N=81) or “other” (patients with any neurologic diagnosis, N=294). Data collected included: age, sex, years of formal education, Mini-Mental Status Examination score from initial visit, Center for Epidemiologic Studies Depression Scale score, Self-Rating of Memory Scale, alcohol consumption, marital status, hours per week of work, past medical history, sleep concerns, and family history of memory concerns. The two groups were compared using t-tests and χ2 tests. The same comparison was done between the same set of “worried well” patients (cognitively normal, N=81) and the subgroup of patients with a diagnosis of Alzheimer’s disease (N=146) from the “other” group. Results: Significant differences included younger age, more formal education, more frequently having previous psychiatric diagnosis and more self-reported alcohol consumption in the “worried well” group. The “worried well” and “Alzheimer’s disease” comparison had the same significant differences as the “worried well” and “other” comparison. Conclusion: We observed a pattern of differences unfold between the “worried well” patients and those with cognitive disease. No one variable was pathognomonic of a “worried well” patient. However, taking all the above into account when evaluating a patient may help clinically.

Background: Intraoperative sedation is often used to facilitate deep brain stimulation (DBS) surgery; however, these sedative agents also suppress microelectrode recordings (MER). To date, there have been no studies that have examined the effects of differing sedatives on surgical outcomes and the success of DBS surgery. Methods: We performed a retrospective study to evaluate the effect of differing sedative agents on postoperative surgical outcomes at 6 months in parkinsonian adult patients who underwent DBS surgery, from January 2004 through December 2014, at one academic center. Surgical outcomes of DBS were evaluated using a simplified Unified Parkinson Diseases Rating Score-III and levodopa dose equivalent reduction at baseline and 6 months postoperatively. Results: We analyzed data from 121 of 124 consecutive parkinsonian patients. Propofol, dexmedetomidine, remifentanil, and midazolam were used individually or in combination. All sedatives were routinely discontinued 20 to 30 minutes before MER, in accordance with our institutional protocol. We found no statistically significant association between the use of individual agent or combination of sedative agents and surgical outcomes at 6 months, the success of DBS, duration of MER, duration of stage 1 procedure, and perioperative complications. Conclusions: Our study showed that the choice of sedative agent was not associated with poor surgical outcomes after DBS surgery using MER and macrostimulation techniques in parkinsonian patients.

Background: Recent advances in neurophysiological techniques have contributed to our understanding of the pathophysiology of Huntington’s disease (HD). Studies of the motor cortical excitability and central motor pathways have shown variable results. Objectives: Our aims were to evaluate the cortical excitability changes in HD using transcranial magnetic stimulation (TMS) and correlate the changes with cognitive impairment. Methods: The study included 32 HD patients and 30 age- and gender-matched controls. The demographic and clinical profiles of the patients were recorded. All subjects were evaluated by TMS and resting motor threshold (RMT), central motor conduction time (CMCT), silent period (SP), short-interval intracortical inhibition (SICI), and intracortical facilitation were determined. A battery of neuropsychological tests was administered to all subjects. Results: The mean age of the patients was 42.1±14.1 years, and that of controls 39.4±12.4 years (p=0.61). There was no significant difference in RMT and CMCT between the two groups. There was a mild prolongation of the contralateral SP in HD, but it was not significant. SICI was significantly reduced in HD (p<0.0001). A significant impairment in attention, verbal fluency, executive function, visuospatial function, learning, and memory was observed in HD patients. However, there was no correlation between cortical excitability changes and cognitive impairment. Conclusions: TMS is a valuable method of evaluating cortical excitability changes in HD. These patients have reduced SICI and significant impairment of cognition in multiple domains.

Background: Parkinson’s disease (PD) is a degenerative disorder of the central nervous system mainly affecting the motor system. Presently, there is no effective and safe drug to treat patients with PD. Ginkgo biloba extract (GBE), obtained from leaves of the Ginkgo biloba tree, is a complex mixture of ingredients primarily containing two active components: flavonoids and terpenoids. In this study, we investigated the effects of GBE on A53T α-synuclein transgenic mice, a PD model that has better simulated the progression of PD patients than other models such as the 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine–induced PD model. Methods: Fifty α-synuclein A53T transgenic mice were fed and treated with GBE, and locomotor activity was detected by pole test, forced swim test, and wire-hang test. The expression of tyrosine hydroxylase and dopamine transporters was detected using immunohistochemistry. Superoxide dismutase activity, glutathione peroxidase activity, and malondialdehyde expression were detected using an assay kit. Results: Our results show that GBE treatment improved locomotor activity and that superoxide dismutase and glutathione peroxidase inhibited the expression of methane dicarboxylic aldehyde and recovered the expression of tyrosine hydroxylase and dopamine transporters. Conclusions: The GBE treatment improved locomotor activity and inhibited the development of PD in the A53T α-synuclein transgenic mice, which may be partly responsible for decreased oxidative damage and maintain the normal dopamine homeostasis.

Background: This study is part of the Innovations in Data, Evidence and Applications for Persons with Neurological Conditions project to understand the strengths, preferences, and needs of persons with neurological conditions living in Canada. Objective: To estimate the prevalence and describe the sociodemographic and clinical characteristics of persons with multiple sclerosis in Canadian home care, nursing home, Complex Continuing Care hospitals, and inpatient mental health care settings. Methods: Cross-sectional study of adults aged 18 years and older with multiple sclerosis (MS; n=11,250) across Canada from 1996 through 2011 using interRAI Resident Assessment Instrument (RAI) comprehensive health assessments (RAI Minimum Data Set 2.0, RAI-Home Care, RAI-Mental Health). Comparisons were made to adults with Alzheimer’s disease and related dementias (n=260,910), other neurological conditions (n=163,578) and non-neurological conditions (n=571,567). Results: The prevalence of MS was highest in Complex Continuing Care hospitals (4125 cases per 100,000 patients), followed by home care (2020 cases per 100,000 patients), nursing homes (1424 cases per 100,000 patients), and mental health settings (138 cases per 100,000 patients). Persons with MS experienced greater impairment in the completion of activities of daily living, pain, pressure ulcers, swallowing difficulty, depression, and anxiety compared with peers within care settings. There were also significant differences between settings, particularly the degree of physical and cognitive impairment experienced by persons with MS. Conclusions: Except for mental health care settings, the prevalence of MS in community, institutional and hospital-based care settings exceeded that of the general population. These data describing the sociodemographic and clinical characteristics of persons with MS may be used to inform clinical practice and policy decisions for persons with MS across the continuum of care.

Objectives: Glioblastoma is a lethal disease in the elderly population. We aimed to evaluate disease and treatment outcomes in the oldest-old patients. Methods: Patients >80 years old with histologically confirmed glioblastoma treated between 2004 and 2009 were identified. We included patients managed with best supportive care (BSC), temozolomide (TMZ) alone, radiotherapy (RT) alone, or concomitantly with TMZ (CRT). Survival outcomes were analyzed using the Kaplan–Meier method. Results: Ultimately, 48 patients were analyzed. Median age and Eastern Cooperative Oncology Group (ECOG) Performance Status were 82 years and 2, respectively. The median Age-Adjusted Charlson Index (AAC) was 6. Gross total and subtotal resections were performed in 16.7% and 18.8% of patients, respectively. Biopsy followed by RT alone was the treatment modality for 23/48 (47.9%), while 17/48 (35.4%) received surgery followed by RT alone or CRT. A total of 8 (16.7%) were managed with BSC after biopsy. Median overall survival (OS) and progression-free survival (PFS) were 4.1 (95% confidence interval [95% CI] 3.3-4.9) and 2.7 (95% CI 1.5-3.9) months, respectively. Improved median OS was observed in those treated with surgical resection followed by RT alone or CRT (7.1 months), compared to biopsy followed by RT alone (4.2 months) or BSC (2.0 months; p=0.002). Surgical resection, age≤85, and AAC<6 were associated with better OS (p=0.032, p=0.031, and p=0.02, respectively). Cause of death was neurological progression in 56% of cases. RT was well-tolerated. Conclusions: PFS and OS outcomes remain poor in the oldest-old patients (>80 years old). Younger age, lower AAC, surgical resection, and adjuvant treatment were associated with improved OS.

Background: Secondary neurotransmitter deficiencies have been reported in several reviews. Our primary aim was to assess the relationship among epilepsy, antiseizure medications, and specific neurotransmitter abnormalities. We also evaluated movement disorders and brain abnormalities via magnetic resonance imaging scans in patients with secondary neurotransmitter defects. Methods: This is a retrospective case series of 376 patients who underwent neurotransmitter analysis at BC Children’s Hospital between 2009 and 2013, for a variety of neurological presentations. The biochemical genetics laboratory database was interrogated for results of cerebrospinal fluid neurotransmitter analyses. Clinical data for patients with abnormal results were collected from the hospital charts. Statistical analysis included one-way analysis of variance, chi-square, and a two-way contingency table. Results: Abnormal neurotransmitter values were identified in 67 (17.8%) patients, two (0.53%) of which were attributable to a congenital neurotransmitter disorder and 11 (16.9%) secondary to other genetic diagnoses. Of 64 patients with secondary abnormal neurotransmitter values, 38 (59%) presented with epilepsy and 20 (31%) with movement disorders. A combination of epilepsy and movement disorder was less frequent. Discussion: Acknowledging the limitations of this retrospective chart review, we conclude that, in our cohort, in addition to patients with movement disorders, a considerable number of patients with epilepsy and epileptic encephalopathy also showed secondary neurotransmitter mono-amine abnormalities. There is no clear relation, however, between clinical phenotype and type of neurotransmitter affected. In addition, no association was identified between the type of antiseizure medications and affected neurotransmitter type. We outline the need for prospective studies to further enrich our understanding of the relation between epilepsy and neurotransmitters with a focus on improving treatments and patient outcomes.

Background: Neurosurgical residents face a unique combination of challenges, including long duty hours, technically challenging cases, and uncertain employment prospects. We sought to assess the demographics, interests, career goals, self-rated happiness, and overall well-being of Canadian neurosurgery residents. Methods: A cross-sectional survey was developed and sent through the Canadian Neurosurgery Research Collaborative to every resident enrolled in a Canadian neurosurgery program as of April 1, 2016. Results: We analyzed 76 completed surveys of 146 eligible residents (52% response rate). The median age was 29 years, with 76% of respondents being males. The most popular subspecialties of interest for fellowship were spine, oncology, and open vascular neurosurgery. The most frequent self-reported number of worked hours per week was the 80- to 89-hour range. The majority of respondents reported a high level of happiness as well as stress. Sense of accomplishment and fatigue were reported as average to high and overall quality of life was low for 19%, average for 49%, and high for 32%. Satisfaction with work-life balance was average for 44% of respondents and was the only tested domain in which significant dissatisfaction was identified (18%). Overall, respondents were highly satisfied with their choice of specialty, choice of program, surgical exposure, and work environment; however, intimidation was reported in 36% of respondents and depression by 17%. Conclusions: Despite a challenging residency and high workload, the majority of Canadian neurosurgery residents are happy and satisfied with their choice of specialty and program. However, work-life balance, employability, resident intimidation, and depression were identified as areas of active concern.

Wilder Penfield and the Montreal Neurological Institute (MNI) are inextricably linked. It was Penfield’s unique idea to create a building with an academic atmosphere wherein basic neuroscience and clinical care of neurological patients would benefit from interaction and mutual support. It is clear that without Penfield that there would be no MNI; however, the role of another Canadian icon, Sir Arthur Currie, in the development of the MNI has heretofore been barely mentioned. The thesis of this paper is that Currie had a critical role in the gestation of the MNI that has generally been ignored.

Canadian contributions to cerebrovascular neurosurgery have been disproportionately large and, with some exceptions, relatively unrecognized. In this review, some of the efforts in the advancement of cerebrovascular neurosurgery by Canadian neurologists and neurosurgeons are described.

Headache is an uncommon symptom in Guillain–Barré syndrome (GBS). We review four clinical settings related to GBS in which headache may be present. We focus on pathophysiological explanations, alerting the clinician to further potential investigations and treatment. Most reports of headache in GBS occur in the context of the posterior reversible encephalopathy syndrome, an increasingly recognized dysautonomia-related GBS complication. Less frequent is headache in the setting of increased intracranial pressure and papilledema (secondary intracranial hypertension), Miller Fisher syndrome, and cerebral venous sinus thrombosis. Rarely, headache can occur secondary to aseptic meningitis from IVIg use.

This case series aimed to describe clinicoradiological, electromyographic, and etiological spectra in palatal tremor (essential=1; symptomatic=26). Patients with symptomatic palatal tremor had 2 to 10 Hz arrhythmic electromyographic bursts, a spectrum of changes in inferior olivary nucleus, with/without lesions in Guillain Mollaret triangle, and varied etiologies (genetic=9, vascular=6, trauma=3, infections=3). Exome sequencing showed variations in POLG, WDR81, NDUFS8, TENM4, and EEF2. Clinical phenotypes of patients with POLG, WDR81, and NDUFS8 variations were consistent with that described in literature. We highlight salient magnetic resonance imaging features, electrophysiological observations, and diverse etiologies in a large cohort of palatal tremor.