Background: Multiple sclerosis (MS) has a profound impact on patients’ health-related quality of life (HRQoL). It is unclear how HRQoL can be best assessed for different purposes. This study aimed to compare two HRQoL questionnaires of differing lengths for feasibility of administration, patient perceptions and psychometric properties. Methods: This was an open-label, 24-month study in 334 patients with relapsing MS treated with subcutaneous interferon β-1a. At baseline and months 6, 12, 18 and 24, patients completed the Multiple Sclerosis International Quality of Life (MusiQoL) and Multiple Sclerosis Quality of Life-54 (MSQOL-54) questionnaires and compared them using an evaluation questionnaire. HRQoL scores over time and psychometric properties (correlations with clinical disease measures, relative validity and responsiveness to change) of the questionnaires were assessed. Results: A minority of patients had missing items on either HRQoL measure. Completion time was significantly shorter for MusiQoL versus MSQOL-54 (p<0.0001). Patients felt that MusiQoL was easier to use than MSQOL-54 but preferred MSQOL-54 in terms of thoroughness. Mean HRQoL scores increased significantly from baseline to 24 months; correlations of both measures were stronger with an anxiety and depression measure than with disability or recent relapse occurrence. Relative validity and responsiveness to change were similar for both instruments. Conclusion: The shorter MusiQoL is suitable for evaluating HRQoL in patients with MS and may be more practical to administer than the more thorough MSQOL-54.

Background: Dimethyl fumerate (DF) is a first line therapy for relapsing remitting multiple sclerosis (RRMS). This retrospective cohort study aims to determine adverse events (AEs) after initiation of DF in a real world clinical setting. Methods: Data from patients at the Calgary MS Clinic with RRMS who initiated DF between July 1, 2013 and December 31, 2014 were analyzed. Demographic, clinical and lab information were collected from patient electronic medical records and the clinic database. Results: This analysis included 170 patients. At treatment initiation mean age was 42.1 years, 75% were women, mean disease duration was 12.5 years, median EDSS was 2.0, and 24% were treatment naïve. Median follow-up was 6.4 months (range: 1.5-17.7). AEs occurred in 101 (59%); the most common were flushing (31%), gastrointestinal (GI) side effects (24%), and elevated liver enzymes (18%). Other less frequent AEs included lymphopenia (lymphocyte count < 0.5) (4%) and proteinuria (4%). DF was discontinued by 17 (10%); median time to discontinuation was 3.1 months. Fifteen (9%) discontinued due to AE. Conclusions: AE associated with DF in a real world clinical setting is comparable to the Canadian monograph for flushing, GI side effects, and lymphopenia but lower for elevated liver enzymes and proteinuria.

Background: The emphasis regarding intracranial neuroendoscopy has been traditionally advocated and focused on the role in pediatric patients, although a significant usage has developed in adult patients. In this study, we examine and contrast the role of predominantly intracranial neuroendoscopy in both a pediatric and adult population with a minimum postprocedure follow-up of 5 years. Methods: A retrospective review was conducted for patients in the two hospitals that manage neurosurgical care for Southern Alberta, Canada, undergoing neuroendoscopic surgery between 1994 and 2008. The pediatric group was defined as age ≤17 years and the adult group as age ≥18 years. Results: A total of 273 patients who underwent a total of 330 procedures with a mean postprocedure follow-up of 12.9 years were identified. There were 161 adult and 112 pediatric patients, and both groups underwent surgery by the same surgeons. The most common procedure was endoscopic third ventriculostomy, accounting for 55% of procedures. One postoperative death occurred in an adult patient. Endoscopic third ventriculostomy success 1-year postprocedure was 81%, with only three late-term failures. Postoperative infection was the most common serious complication (two pediatric/four adult patients). Adult and pediatric patients had similar major complication rates (4.2% vs 5.7%, p=0.547). Conclusions: Neuroendoscopy overall had a similar role in both pediatric and adult neurosurgical populations, with the most commonly associated complication being infection. Neuroendoscopy is an important therapeutic modality in the management of appropriate adult patients.

Background: In the past two decades, there has been increasing evidence to suggest that trigeminal neuralgia (TN) may be linked to a dysfunction of the autonomic nervous system (ANS). The aim of the present study was to formally test this hypothesis by comparing the reactivity of the ANS to experimental pain in a population of TN patients and healthy controls. Methods: Twelve patients diagnosed with classical TN and 12 healthy controls participated in the study. Cardiac activity was assessed while participants were instructed to rest and again during a cold pressor test (CPT). Heart rate variability analyses were performed off-line to obtain parasympathetic (high-frequency) and sympathetic (low-frequency) indices. Results: At baseline, ANS measures did not differ between healthy controls and TN patients, and both groups showed a similar increase in heart rate during the CPT (all p values >0.05). However, TN patients showed a greater increase in cardiac sympathetic activity and a greater decrease in cardiac parasympathetic activity during CPT compared with healthy controls (all p values <0.05). Importantly, changes in sympathetic reactivity, from baseline to CPT, were negatively associated with the number of pain paroxysms experienced each day by TN patients in the preceding week (r=−.58, p<0.05). Conclusions: These results suggest that TN, like many other short-lasting, unilateral facial pain conditions, is linked to ANS alterations. Future studies are required to determine if the altered ANS response observed in TN patients is a cause or a consequence of TN pain

Lymphocytic choriomeningitis virus (LCMV) carried and secreted by mice, infects great numbers of people. LCMV infection acquired during childhood or adulthood is usually moderately symptomatic with a full recovery. When the infection occurs prenatally, it results in a wide spectrum of severe brain lesions described mainly on imaging. Neuropathological data have never been reported.

We present 2 fetuses with a prenatal diagnosis of microcephaly with ventriculomegaly, abnormal gyration, and ponto-cerebellar hypoplasia in one case. Parents elected to terminate the pregnancy. A complete autopsy demonstrated no dysmorphic features, no visceral or skeletal malformation. Histological examination of viscera did not show any significant lesion.

Neuropathological examination confirmed microcephaly and ventriculomegaly with a thick yellowish band surrounding the ventricles. Identical histological lesions were observed in both cases associating a polymicrogyria and a diffuse necrosis of parenchyma with massive calcifications all around the ventricles. The most characteristic feature was the unusual aspect of necrosis, distinct from that observed in other infections, characterized by a finely granular appearance looking like sand. Small lymphocytic infiltrates were observed in the leptomeninges and in the choroid but not in the retina. The congenital LCMV infection was confirmed by serologic testing.

This study confirms the strong neurotropism of LCMV and demonstrates that prenatal infection has some particular features such as absent systemic signs, and distinct appearance of the necrosis that allow to distinguish it from other congenital infections and other non infectious conditions.

Cerebral hyaline astrocytic inclusions (HAI) have been observed in a subset of patients with epilepsy, structural brain anomalies, and developmental delay. We present a case of a 2.5-year-old male with epilepsy and global developmental delay. Chromosomal microarray detected a copy loss at 22q13 that resulted in a partial deletion of SHANK3 gene. The EEGs revealed seizure activity arising from left frontal central region. Invasive video electrocorticography captured clusters of epileptic spasms, all originating from left antero-lateral frontal lobe rostral to the motor cortex. We utilized routine histology to identify the inclusions and mapped their distribution in the resected portion of the cortex against electrocorticographic data. Histologic analysis revealed the presence of HAI in the posterio-medial portion of the resected cortex, which corresponded to the site of seizure generalization. HAI were present at the resection margin. Immunohistochemistry was largely non-contributory. HAI is a rare but emerging entity that is associated with epilepsy. To our knowledge, the distribution of inclusions in HAI has never been mapped to electrophysiologic data. In our case, seizure generalization correlated with the inclusions distribution. This suggests that the inclusions may: 1) play a role in epileptogenesis; or, 2) be a biomarker of disease distribution. Finally, the presence of the HAI at the resection margin may foreshadow future seizure activity in this patient.

Background: Although current pain-evoked electroencephalographic (EEG) studies provide valuable information regarding human brain regions involved in pain, they have mostly considered neuronal responses which oscillate in phase following a painful event. In many instances, cortical neurons respond by generating bursts of activity that are slightly out of phase from trial-to-trial. These types of activity bursts are known as induced brain responses. The significance of induced brain responses to pain is still unknown. Methods: In this study, 23 healthy subjects were given both non-painful and painful transcutaneous electrical stimulations in separate testing blocks (stimulation strength was kept constant within blocks). Subjective intensity was rated using a numerical rating scale, while cerebral activity tied to each stimulation was measured using EEG recordings. Induced brain responses were identified using a time frequency wavelet transform applied to average-removed single trials. Results: Results showed a pain-specific burst of induced theta activity occurring between 180 and 500 ms post-shock onset. Source current density estimations located this activity within the dorsolateral prefrontal cortex (DLPFC, bilaterally), however, only right DLPFC activity predicted a decrease in subjective pain as testing progressed. Conclusion: This finding suggests that non-phase locked neuronal responses in the right DLPFC contribute to the endogenous attenuation of pain through time. Perspective: This article presents neuroimaging findings demonstrating that, in response to pain, non-phase locked bursts of theta activity located in the right dorsolateral prefrontal cortex are associated with a progressive decrease in subjective pain intensity, which has potentially important implications regarding how humans endogenously control their experiences of pain.

Objective: Our knowledge of disease mechanisms in epilepsy is biased by findings originating from cross-sectional studies and advanced stages of epilepsy. We provide a new perspective by collecting systematically longitudinal data from patients who present in early stages (ES). Methods: The Halifax First Seizure Clinic, founded in 2008, uses a comprehensive multimodal data basis addressing clinical presentation, neuroimaging, EEG findings, genetics, cognition, comorbidities, social parameters, and life style. Follow-up visits are 6, 12 and 24 months. Results: Out of 575 patients we identified 3 subgroups 1) Strictly first seizure, n=187, 2) New-onset epilepsy (> 1 seizure < 12 months), n=149, and 3) Newly-diagnosed epilepsy (seizures > > 12 months), n=50. 189 patients were excluded (not proven seizure or other conditions e.g syncope etc.). Our interim analyses suggest: A) pharmacoresistance presents in highly diverse patterns and is rarer than expected in ES, B) Congenital malformations seem to have an excellent treatment prognosis in ES, C) Marijuana consumption is significantly more prevalent at initial assessment (comparison general population), D) Preceding psychiatric comorbidities associated with reduced amygdalar volume may be a predictor for seizure recurrence. Conclusions: The preliminary and illustrative findings of our pilot study challenge current concepts of disease evolution in epilepsy.

Background: Appropriate use criteria (AUC; Johnson et al, 2013) provide guidelines for selecting patients for whom amyloid PET could be useful. This study evaluated the impact of amyloid PET on diagnosis/management in patients likely to meet AUC. Methods: We examined 229 cases from a completed study of florbetapir amyloid PET (FBP-PET) in patients with a cognitive decline evaluation in whom Alzheimer’s Disease (AD) was suspected, but with <85% confidence in the diagnosis. All cases received a provisional diagnosis and management prior to FBP-PET. Information for 172 cases after 3-months’ follow-up was also available on actual diagnosis/management post-FBP-PET. Cases were classified as likely meeting AUC (AUC-like) or not. Results: 125/229(55%) subjects were AUC-like. NonAUC cases included typical AD, Mild Cognitive Impairment (MCI) due to AD, Cognitive Decline without objective evidence of impairment (CD) and dementia or cognitive impairment with specific nonAD diagnosis. 59/125(47%) AUC-like cases were amyloid positive (Aβ+). Among nonAUC cases, 29% (CD), 49%(MCI due to AD), 53%(non-AD) and 73%(typical AD) were Aβ+. Of 172 cases with follow-up information, diagnosis/management changed after FBP-PET in 58%/88% and 45%/77% of AUC-like and nonAUC, respectively. Conclusions: FBP-PET altered diagnosis/management in patients selected according to AUC. Additionally, AUC generally excluded patients with a relatively high (typical AD) or low (CD) probability of Aβ+ scan.