To determine whether optic disc hemorrhages (ODH) and cotton wool spots (CWS) at presentation are associated with worse visual outcomes in pediatric patients with idiopathic intracranial hypertension (IIH).

Retrospective institutional review of 100 eyes of 50 consecutive pediatric IIH patients (aged 16 years or less) who had baseline optic disc photographs before or within 30 days of their diagnostic lumbar puncture and initiation of medical treatment. Optic disc photographs were independently graded by three ophthalmologists in a standardized manner. Visual function was assessed using visual acuity (VA) and visual field grade (VFG).

At least one ODH was found in 41% of eyes, at least one CWS was found in 27% of eyes, and 20% of eyes had both ODH and CWS. At presentation, Frisén grade was associated with the presence of CWS (p = 0.013) and showed no association with ODH (p = 0.060). When controlling for Frisén grade, ODH and CWS were not associated with worse VA or VFG at final follow-up. Severe ODH were associated with worse VA and VFG at presentation (p < 0.03), but not at final follow-up. Severe CWS at presentation was strongly associated with a worse Humphrey mean deviation of 5.0 dB (95% confidence interval 1.6–8.3) at final follow-up (p = 0.002).

When controlling for the severity of papilledema, ODH do not provide any additional prognostic value in pediatric IIH patients. Frisén grade and severe CWS at presentation were independently associated with worse visual outcomes at the final follow-up.

Rapid eye movement (REM) sleep behavior disorder (RBD) and REM sleep without atonia (RWA) have assumed much clinical importance with long-term data showing progression into neurodegenerative conditions among older adults. However, much less is known about RBD and RWA in younger populations. This study aims at comparing clinical and polysomnographic (PSG) characteristics of young patients presenting with RBD, young patients with other neurological conditions, and normal age-matched subjects.

A retrospective chart review was carried out for consecutive young patients (<25 years) presenting with clinical features of RBD; and data were compared to data from patients with epilepsy, attention deficit hyperactivity disorder (ADHD), and autism, as well as normal subjects who underwent PSG during a 2-year-period.

Twelve patients fulfilling RBD diagnostic criteria, 22 autism patients, 10 with ADHD, 30 with epilepsy, and 14 normal subjects were included. Eight patients with autism (30%), three with ADHD (30%), one with epilepsy (3.3%), and six patients who had presented with RBD like symptoms (50%) had abnormal movements and behaviors during REM sleep. Excessive transient muscle activity and/or sustained muscle activity during REM epochs was found in all patients who had presented with RBD, in 16/22 (72%) autistic patients, 6/10 (60%) ADHD patients compared to only 6/30 (20%) patients with epilepsy and in none of the normal subjects.

We observed that a large percentage of young patients with autism and ADHD and some with epilepsy demonstrate loss of REM-associated atonia and some RBD-like behaviors on polysomnography similar to young patients presenting with RBD.

Early consciousness recovery after cardiac arrest (CA) is one of the most explicit and self-evident prognostic factors for clinical outcomes. We aimed to evaluate the prognostic value of electroencephalography (EEG) phenotypes according to the American Clinical Neurophysiology Society’s Critical Care EEG classification for predicting early recovery after CA.

Consecutive patients admitted to the ICU after CA were enrolled. We analyzed Glasgow Coma Scale (GCS) score within 10 days after CA and evaluated mortality within 28 days according to EEG pattern subtype.

Among the total of 71 patients, 9 had periodic discharges (PDs) EEG pattern, 4 had rhythmic delta activity (RDA), 8 had spike-and-wave (SW), 22 had low voltage, 5 had burst suppression, and 23 had other EEG patterns. Initial GCS scores, GCS scores 3 days after CA (or 3 days after targeted temperature management [TTM]), and 10 days after CA (or 10 days after TTM) were significantly different among EEG subtypes (p < 0.001, respectively) (Table 2). GCS scores were significantly higher in RDA and the other EEG group compared to the PDs, SW, low voltage, and burst suppression groups (p < 0.001). Significant group × time interactions were observed for the follow-up period between EEG phenotypes (p < 0.001) demonstrating the most increase in the other EEG pattern group.

Consciousness states were significantly worse in the PDs, SW, burst suppression, and low-voltage groups compared to the RDA and the other EEG pattern within 10 days after CA. The degree of consciousness recovery differed significantly by EEG pattern subtype within 10 days.

Little is known about the potential systemic effects of ankylosing spondylitis (AS) on the nervous system. We designed a study aiming to assess the frequency and clinical predictors of cognitive impairment in AS patients.

We carried out a cross-sectional case–control study composed of consecutive patients with AS. Trained and blinded interviewers registered clinical-epidemiological data and applied a standardized neurological assessment for each subject of the study. At baseline, functional limitations were characterized using the Health Assessment Questionnaire. Cognitive impairment was evaluated with the Brief Cognitive Screening Battery, the Montreal Cognitive Assessment, and the Clinical Dementia Rating, while neuropsychiatric symptoms were investigated with the Hospital Anxiety and Depression Scale. Healthy controls were matched for age, educational attainment, sex, and comorbidities. We compared the neurological outcomes between case and controls, and we determined the clinical predictors of cognitive decline.

We included 40 patients (mean: 49.3 years) with AS and 40 healthy controls (mean: 48.8 years) in our study. In Brief Cognitive Screening Battery, patients with AS presented a statistically significant poor performance in the clock drawing test and in the verbal fluency. The mean Montreal Cognitive Assessment (MoCA) scores were significantly lower in AS subjects compared to the control group. Also, the prevalence of subjects classified as cognitively impaired according to MoCA was significantly higher in the AS group (90.0% vs. 57.5%, p = 0.02). Moreover, neuropsychiatric symptoms were more prevalent in AS patients. Worse functional limitations were associated with poor cognitive performance as well.

Patients with AS might be more vulnerable to cognitive decline.

Serotonergic dysfunction may play an important role in motor and nonmotor symptoms of Parkinson’s disease (PD). The loudness dependence of auditory evoked potentials (LDAEP) has been used to evaluate serotonergic activity. Therefore, this study aimed to determine central serotonergic activity using LDAEP in de novo PD according to the age at onset and changes in serotonergic activity after dopaminergic treatment.

A total of 30 patients with unmedicated PD, 16 in the early-onset and 14 in the late-onset groups, were enrolled. All subjects underwent comprehensive neurological examination, laboratory tests, the Unified Parkinson’s Disease Rating Scale, and LDAEP. The LDAEP was calculated as the slope of the two N1/P2 peaks measured at the Cz electrode, first at baseline conditions (pretreatment) and a second time after 12 weeks (post-treatment) following dopaminergic medications.

The absolute values of pretreatment N1/P2 LDAEP (early-onset: late-onset, 0.99 ± 0.68: 1.62 ± 0.88, p = 0.035) and post-treatment N1 LDAEP (early-onset: late-onset, −0.61 ± 0.61: −1.26 ± 0.91, p = 0.03) were significantly lower in the early-onset group compared with those of the late-onset group. In addition, a higher value of pretreatment N1/P2 LDAEP was significantly correlated with the late-onset group (coefficient = 1.204, p = 0.044). The absolute value of the N1 LDAEP decreased after 12 weeks of taking dopaminergic medication (pretreatment: post-treatment, −1.457 ± 1.078: −0.904 ± 0.812, p = 0.0018).

Based on the results of this study, LDAEP could be a marker for serotonergic neurotransmission in PD. Central serotonergic activity assessed by LDAEP may be more preserved in early-onset PD patients and can be altered with dopaminergic medication.

Our purpose was to determine the role of CHRNA4 and CHRNB2 in insular epilepsy.

We identified two patients with drug-resistant predominantly sleep-related hypermotor seizures, one harboring a heterozygous missense variant (c.77C>T; p. Thr26Met) in the CHRNB2 gene and the other a heterozygous missense variant (c.1079G>A; p. Arg360Gln) in the CHRNA4 gene. The patients underwent electrophysiological and neuroimaging studies, and we performed functional characterization of the p. Thr26Met (c.77C>T) in the CHRNB2 gene.

We localized the epileptic foci to the left insula in the first case (now seizure-free following epilepsy surgery) and to both insulae in the second case. Based on tools predicting the possible impact of amino acid substitutions on the structure and function of proteins (sorting intolerant from tolerant and PolyPhen-2), variants identified in this report could be deleterious. Functional expression in human cell lines of α4β2 (wild-type), α4β2-Thr26Met (homozygote), and α4β2/β2-Thr26Met (heterozygote) nicotinic acetylcholine receptors revealed that the mutant subunit led to significantly higher whole-cell nicotinic currents. This feature was observed in both homo- and heterozygous conditions and was not accompanied by major alterations of the current reversal potential or the shape of the concentration-response relation.

This study suggests that variants in CHRNB2 and CHRNA4, initially linked to autosomal dominant nocturnal frontal lobe epilepsy, are also found in patients with predominantly sleep-related insular epilepsy. Although the reported variants should be considered of unknown clinical significance for the moment, identification of additional similar cases and further functional studies could eventually strengthen this association.

Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.

The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials.

The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner.

Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.

Identifying risk factors and mortality of individuals with Alzheimer’s disease (AD) could have important implications for the clinical management of AD.

This pilot study aimed to examine the overall mortality of AD patients over a 10-year surveillance period in Shanghai, China. This study is an extension of our previous investigation on mortality of neurodegenerative diseases.

One hundred and thirty-two AD patients recruited from the memory clinics of two hospitals in Shanghai in 2007 were followed up until December 31, 2017 or death, representing a follow-up period of up to 10 years. Overall standardized mortality ratios (SMRs) were calculated, and predictors for survival at recruitment were estimated.

Sixty-seven patients had died by December 31, 2017, and the SMR at 10 years of follow-up was 1.225 (95% confidence interval 0.944–1.563). Employing Cox’s proportional hazard modeling, lower Mini-Mental State Examination score, and comorbid diabetes predicted poor survival in this cohort.

This pilot study suggests a similar survival trend of patients with AD compared to the general population in Shanghai urban region. Poor cognitive status and comorbid diabetes had a negative impact on the survival of AD patients.

Multiple sclerosis (MS) is the most common cause of neurological disability, other than trauma, among young adults of reproductive age. In contrast to the past, today there is very little lag time from clinical onset to diagnosis. Disease-modifying therapies are also now available outside of clinical trials. However, there is very little evidence-based population data to help an individual with MS make informed decisions with respect to reproductive options.

The objective of this study is to develop a Canada-wide, prospective population-based registry of women with MS who are either trying to become pregnant and/or have become pregnant.

The study represents a “real-world” scenario. Women with MS are invited to participate, regardless of clinical course, therapy, disease duration, and/or disability. The methodology to develop such a registry is very complex making it imperative to understand the design and rationale when interpreting results for clinical purposes.

This paper is a comprehensive discussion of the study rationale and methodology.

The study is ongoing, with over 100 potential participants. Numerous future publications are envisioned as the study progresses. The present paper is thus designed to be the key referral paper for subsequent publications in which it will not be possible to provide the necessary detailed information on rationale and methodology.

Many neurosurgeons pursue graduate degrees as part of their training. In some jurisdictions, graduate degrees are considered a necessary condition of employment in academic neurosurgery. However, the relationship between possession of a graduate degree and eventual research productivity is not well established. We used bibliometric methods to analyze publications from academic Canadian neurosurgeons, with an emphasis on level of graduate training.

All neurosurgeons holding academic appointments at Canadian institutions from 2012–2016 were included. Over that time frame, Scopus was used to quantify the number of papers, number of citations, 5-year h-index and 5-year r-index, CiteScore, authorship position, and paper type (clinical or basic science). Publication output was compared between neurosurgeons grouped as MD-only, MD-Masters, or MD-PhD.

In total, 2557 abstracts from 131 Canadian neurosurgeons were analyzed. We found that MD-Masters neurosurgeons published significantly more total papers, clinical papers, and first/last author papers than MD-only neurosurgeons. MD-PhD neurosurgeons had the same findings, in addition to more basic science papers, in journals with a higher CiteScore, 5-year h-index, and 5-year r-index than both other groups. These results were preserved even with significant outliers removed. There was no difference if graduate degrees were obtained before or after starting residency. There was no correlation with career length and number of recent papers published.

The attainment of a graduate degree has an important association with future publication productivity for academic neurosurgeons. These data should be useful for hiring committees considering the value of graduate degrees from applicants for positions in academic neurosurgery.

Patients diagnosed with glioblastoma (GBM) are treated with surgery followed by fractionated radiotherapy with concurrent and adjuvant temozolomide. Patients are monitored with serial magnetic resonance imaging (MRI). However, treatment-related changes frequently mimic disease progression. We reviewed a series of patients undergoing surgery for presumed first-recurrence GBM, where pathology reports were available for tissue diagnosis, in order to better understand factors associated with a diagnosis of treatment-related changes on final pathology.

Patient records at a single institution between 2005 and 2015 were retrospectively reviewed. Pathology reports were reviewed to determine diagnosis of recurrent GBM or treatment effect. Survival analysis was performed interrogating overall survival (OS) and progression-free survival (PFS). Correlation with radiation treatment plans was also examined.

One-hundred-twenty-three patients were identified. One-hundred-sixteen patients (94%) underwent resection and seven underwent biopsy. Treatment-related changes were reported in 20 cases (16%). These patients had longer median OS and PFS from the time of recurrence than patients with true disease progression. However, there was no significant difference in OS from the time of initial diagnosis. Treatment effect was associated with surgery within 90 days of completing radiation. In patients receiving radiation at our institution (n = 53), larger radiation target volume and a higher maximum dose were associated with treatment effect.

Treatment effect was associated with surgery nearer to completion of radiation, a larger radiation target volume, and a higher maximum point dose. Treatment effect was associated with longer PFS and OS from the time of recurrence, but not from the time of initial diagnosis.

Basal ganglia (BG) lesions are rarely reported in patients with uremia and may manifest by movement disorders. However, their exact incidence and pathogenesis have not been extensively studied. This study aimed to determine the frequency, types, risk variables (clinical, laboratory, and imaging), and manifestations of BG lesions with uremia and patients’ neurologic outcomes.

This observational study included 70 adults (mean age: 45.87 ± 3.36 years; duration of uremia: 5.5 ± 1.5 years). They underwent extensive evaluations (clinical, laboratory, and neuroimaging) and had prospectively evaluated clinically every 3 months for 2 years. Repeated magnetic resonance imaging (MRI) brains were done to patients with movement disorders and correlated with their neurologic outcomes.

BG lesions were found in 15 patients (21.4%) and 6 (8.6%) had movement disorders [Parkinsonism (n = 4), choreo-dystonia (n = 1) and dystonia (n = 1)] after the onset of uremia (mean = 10 months). There were no characteristic risk variables that distinguished patients with movement disorders from those without. Five developed movement disorders prior to the period of the study and one was de novo. The majority was females and had diabetes and higher frequencies of abnormal renal dysfunction, metabolic derangements, and white matter hyperintensities in MRIs. Movement disorders persisted in all patients despite the resolution of neuroimaging in three patients.

There is no clear threshold for renal failure to result in movement disorders due to BG lesions. The clinical outcome is variables depending on each patient’s comorbidities and complications. Persistent neuronal damage (due to uremic toxins/metabolic/nutritional and ischemic/microvascular factors) has been suggested as the cause of poor neurologic outcomes.

Recent investigations now suggest that cerebrovascular reactivity (CVR) is impaired in Alzheimer’s disease (AD) and may underpin part of the disease’s neurovascular component. However, our understanding of the relationship between the magnitude of CVR, the speed of cerebrovascular response, and the progression of AD is still limited. This is especially true in patients with mild cognitive impairment (MCI), which is recognized as an intermediate stage between normal aging and dementia. The purpose of this study was to investigate AD and MCI patients by mapping repeatable and accurate measures of cerebrovascular function, namely the magnitude and speed of cerebrovascular response (τ) to a vasoactive stimulus in key predilection sites for vascular dysfunction in AD.

Thirty-three subjects (age range: 52–83 years, 20 males) were prospectively recruited. CVR and τ were assessed using blood oxygen level-dependent MRI during a standardized carbon dioxide stimulus. Temporal and parietal cortical regions of interest (ROIs) were generated from anatomical images using the FreeSurfer image analysis suite.

Of 33 subjects recruited, 3 individuals were excluded, leaving 30 subjects for analysis, consisting of 6 individuals with early AD, 11 individuals with MCI, and 13 older healthy controls (HCs). τ was found to be significantly higher in the AD group compared to the HC group in both the temporal (p = 0.03) and parietal cortex (p = 0.01) following a one-way ANCOVA correcting for age and microangiopathy scoring and a Bonferroni post-hoc correction.

The study findings suggest that AD is associated with a slowing of the cerebrovascular response in the temporal and parietal cortices.

Transthyretin familial amyloid polyneuropathy (TTR-FAP) is caused by a mutation in the transthyretin (TTR) gene. Although classically described as rapidly progressive and life-threatening, recent studies on TTR-FAP show significant genetic and phenotypic heterogeneity depending on geographic localization. In light of new therapeutic advances and their implication for patient management, the aim of our study was to determine the prevalence of TTR-FAP within patients with idiopathic neuropathy in a North American population.

We sequenced the TTR gene in a cohort of patients with idiopathic neuropathy. Genetic screening was performed in 110 patients from two neuromuscular clinics in Montreal, Canada.

No variants of unknown significance or pathogenic mutations were detected in the TTR gene.

Our study confirms that TTR-FAP is a rare entity in our patient population, and that diagnostic yield of screening all patients with idiopathic neuropathy is very low.

To explore what elective students learn about the specialty of Neurology.

A prospective qualitative study using pre- and post-elective written questionnaires.

Analysis concentrated on three main themes: What did students learn about the specialty of Neurology? What would they change about their experience? Did their opinions change? Major findings were (i) pre- and post-elective the most frequent response for “what is the best thing about Neurology?” was the “process of localization” and (ii) post-elective students were less likely to cite the challenge or problem-solving aspect of Neurology as the best thing while more emphasized the importance of the physical exam and the variety of cases. (iii) Students were most surprised by the scope of neurological practice. (iv) They would diversify the setting of their elective to include less time spent in the emergency room and more time in clinic. (v) The perception of Neurology as a specialty in which patients have a poor prognosis was the opinion that changed the most.

Showcasing the diversity of cases and careers in Neurology may be a useful strategy to increase interest in the specialty and reduce neurophobia. Lectures or small groups early in medical school should concentrate on clear examples of common neurological conditions and emphasize the role of general neurologists and subspecialists involved in patient care. Whenever possible students should rotate through different clinics and not concentrate exclusively on emergency room and in-patient cases.

The response of chronic inflammatory demyelinating polyneuropathy (CIDP) to intravenous immunoglobulins (IVIgs) treatment is well established. However, it remains unclear whether patients not responding to two IVIg treatments or those whose condition stabilizes (ICE trial) may benefit from additional doses. We aim to identify the time period required to reach maximal strength gains from IVIg treatment.

Retrospective chart review of 14 patients with CIDP was performed. Change in handgrip (HG), Knee extension (KE), elbow flexion, and dorsiflexion was analyzed with a dynamometer during IVIg therapy. Strength improvements in Nm or kg, cumulative grams (g) of IVIg, and time in days required for maximal strength recovery were determined per function (± standard error of the mean). Ancillary therapy was recorded for all patients.

Improvements in strength of each function were significant (p < 0.05). Earliest improvement was in HG (137.07 ± 21.23) and latest in KE (238.15 ± 38.9). Majority of patients improved by 200 days of therapy. HG required the lowest cumulative grams of IgG (561.71 ± 97.21) and KE the most (798 ± 120.7).

Our study has demonstrated the effectiveness of multiple treatments with IVIg to reach significant improvement in strength. Different muscle groups manifested different time dependency, reflecting the requirement of variable amounts of IVIg. Improvement was identified on an ongoing basis, with therapy lasting between 20.2 and 37.3 weeks, requiring between 562 and 798 g of IVIg.

Diagnostic delay in amyotrophic lateral sclerosis (ALS) is common. In a recent Canadian study evaluating provincial differences in care, Saskatchewan had the longest delay at 27 months. Since Saskatchewan has a large rural population, this study sought to determine whether geographically determined access to a neurologist at tertiary centers could be contributing to this lengthy delay.

A retrospective chart review of 171 patients seen in the ALS clinic in Saskatoon, Saskatchewan was performed. Urban or rural location, distance from nearest tertiary center, and clinically relevant data were collected.

There was no difference between urban and rural populations for delay in symptom onset to diagnosis. For rural patients, linear regression modeling did not uncover a significant relationship between distance from tertiary center and time to diagnosis. Additionally, there were no differences between urban and rural dwellers either for referral or utilization of feeding tube, noninvasive ventilation, riluzole, or communication devices. Contrary to the previous data showing a 27-month diagnostic delay in Saskatchewan, our study which included a larger provincial population found the mean diagnostic delay was 16.6 months.

This study did not uncover differences in diagnostic delay or ALS care between urban and rural dwellers. Further study is required to determine reproducibility of results.