Detecting seasonal trends in optic neuritis within the Ottawa region.

OBJECTIVE: In this study we aim to determine seasonal patterns underlying optic neuritis (ON) onset that may provide valuable epidemiologic information and help delineate causative or protective factors. DESIGN: Single-centre retrospective chart review. METHODS: A database search of centralized electronic health records was completed using diagnostic codes employed at the Ottawa Eye Institute for data collection. Charts were reviewed for documentation supporting a diagnosis of ON falling into the following categories: multiple sclerosis ON and clinically isolated syndrome ON, myelin oligodendrocyte glycoprotein ON, neuromyelitis optica ON, and idiopathic ON. Date of onset, biological sex, and age were extracted from each chart. Data were analyzed for calculation of frequency by season and overall pooled seasonal trends of all cases of ON. RESULTS: From the 218 included patients with ON, there was no statistically significant seasonal correlation. The overall trend of ON was lowest in winter and spring (22% and 23%, respectively) and highest in summer and fall (28% and 27% respective). Divided further, multiple sclerosis ON or clinically isolated syndrome ON rates (n = 144) were lowest in the spring (21%) and highest in fall (29%); myelin oligodendrocyte glycoprotein ON rates (n = 25) were lowest in winter (16%) and highest in summer and fall (both at 32%); neuromyelitis optica ON rates (n = 16) were lowest in fall (12.5%) and highest in winter and summer (both at 31.25%); and idiopathic ON rates (n = 33) were lowest in fall (18%) and highest in spring (33%). CONCLUSIONS: The overall ON seasonal trend appears to have a predilection for the summer and fall months, which may be explained by warmer weather and viral infections as risk factors for multiple sclerosis relapse during those seasons.

Longitudinal Patient Outcomes in Chronic Dizziness: A Scoping Review.

BACKGROUND: Chronic dizziness can cause significant functional impairment. Outcome measures used in this patient population have not been examined systematically. Consequently, providers lack consensus on the ideal outcome measures to assess the impact of their interventions. OBJECTIVE AND METHODS: We conducted a scoping review to summarize existing literature on outcomes in chronic dizziness (with a minimum of 6 mo of patient follow-up). Among other details, we extracted and analyzed patient demographics, medical condition(s), and the specific outcome measures of each study. RESULTS: Of 19,426 articles meeting the original search terms, 416 met final exclusion after title/abstract and full-text review. Most studies focused on Ménière's disease (75%) and recurrent benign paroxysmal positional vertigo (21%). The most common outcome measures were hearing (62%) and number of attacks by American Academy of Otolaryngology-Head & Neck Surgery criteria (60%). A minority (35%) looked formally at quality-of-life metrics (Dizziness Handicap Index or other). CONCLUSIONS: Ménière's disease and benign paroxysmal positional vertigo are overrepresented in literature on outcome assessment in chronic dizziness. Objective clinical measures are used more frequently than quality-of-life metrics. Future work is needed to identify the optimal outcome measures that reflect new knowledge about the most common causes of chronic dizziness (including persistent postural-perceptual dizziness and vestibular migraine) and consider what is most important to patients.

Current state of headache training within Canadian Neurology Residency program: a national survey.

BACKGROUND: Headache disorders are the most common neurological disorders worldwide. Despite their widespread prevalence and importance, the topic of headache is inconsistently taught at both the undergraduate and postgraduate levels. The goal of this study is to establish a better picture of the current state of Headache Medicine (HM) training in Neurology postgraduate programs in Canada and describe the impact of the current pandemic on training in this domain. METHODS: Online surveys were sent to senior residents of adult Neurology programs in Canada. We also conducted telephone interviews with Neurology Program Directors. Descriptive statistics were analyzed, and thematic analysis was used to review free text. RESULTS: A total of 36 residents, and 3 Program Directors participated in the study. Most of the teaching in HM is done by headache specialists and general neurology faculty. Formal teaching is mainly given during academic half day. Most of the programs expose their residents to Onabotulinum toxin A injections and peripheral nerve blocks, but they don't offer much formal teaching regarding these procedures. Residents consider HM teaching important and they would like to have more. They don't feel comfortable performing interventional headache treatments, despite feeling this should be part of the skillset of a general neurologist. CONCLUSION: Our study is the first to establish the current state of headache teaching in post-graduate neurology programs as perceived by trainees and program directors in Canada. The current educational offerings leave residents feeling poorly prepared to manage headaches, including procedural interventions. There is a need to diversify the source of teaching, so the educational burden doesn't lie mostly upon Headache specialists who are already in short supply. Neurology Residency programs need to adapt their curriculum to face the current need in HM.

Resident Match During the COVID Pandemic: How Have Neurology Programs Adapted? - A Survey.

BACKGROUND: We aimed to evaluate the perceived effectiveness of interventions implemented by Canadian neurology residency programs for the 2020-2021 iteration of the Canadian Resident Matching Service (CaRMS). METHODS: A cross-sectional survey was distributed to Canadian neurology residency programs and final-year Canadian medical students who applied to at least one neurology program during the 2020-2021 match cycle. The surveys evaluated pre-interview and interview period interventions implemented by Canadian neurology residency programs and accessed by medical students. RESULTS: Thirty-five medical students and 13 out of 15 institutions in Canada with neurology residency programs responded to the survey. Multiple adaptations were implemented, including social media advertisement, web-based platforms, pre-interview information sessions, and teaching sessions, with all surveyed programs implementing at least two virtual interventions. We found that all interventions were perceived as adequate by a majority (>60%) of medical students, with pre-interview period virtual information sessions perceived as effective by the largest proportion of respondents. All Canadian neurology residency programs held virtual interviews for the 2020-2021 cycle, and most programs utilized the same interview structure as prior years. There was discordance between residency program stakeholders and medical students on the most helpful interview period modality. Medical students found the hospital tours and information sessions most valuable, whereas program stakeholders perceived the virtual socials and interviews as most helpful. CONCLUSION: The COVID-19 pandemic has led to innovative adaptations implemented by Canadian neurology residency programs, which were seen as effective by both medical students and program stakeholders.

Risk of stroke is low after transient ischemic attack presentation with isolated dizziness.

OBJECTIVE: Stroke presenting as dizziness is a diagnostic challenge in frontline settings, given the multitude of benign conditions that present similarly. The risk of stroke after episodic dizziness is unknown, leading to divergent guidance on optimal workup and management. Prior TIA risk scores have shown a history of dizziness is a negative predictor of subsequent stroke. Our objective was to assess the subsequent stroke risk within 90 days following emergency department assessment (ED) for isolated dizziness diagnosed as TIA during the index visit. METHODS: We conducted prospective, multicenter cohort studies at 13 Canadian EDs over 11 years. We enrolled patients diagnosed with TIA and compared patients with isolated dizziness to those with other neurological deficits. Our primary outcome was subsequent stroke within 90 days. Secondary outcomes were subsequent stroke within 2, 7, and 30 days, respectively, as well as subsequent TIA within 90 days. RESULTS: Only 4/483 (0.8%) patients with isolated dizziness had a stroke within 90 days compared to 320/11024 (2.9%) of those with any focal neurological sign or symptom (RR 0.29, 95% CI 0.11-0.76). Over the first 90 days, the two groups differ significantly in their probability of stroke (p = 0.007). Subsequent TIA was also significantly less common in the isolated dizziness group (1.7% vs. 5.6%, p = 0.001) with a relative risk of 0.30 (95% CI 0.15-0.60). CONCLUSION: The risk of subsequent stroke following ED presentation for TIA is low when the presenting symptoms are isolated dizziness.

RéSUMé: OBJECTIF: Les accidents vasculaires cérébraux (AVC) se présentant sous forme de vertiges constituent un défi diagnostique en première ligne, étant donné la multitude d'affections bénignes qui se présentent de la même manière. Le risque d'accident vasculaire cérébral (AVC) après des vertiges épisodiques est inconnu, ce qui donne lieu à des conseils divergents sur le bilan et la prise en charge optimaux. Des scores de risque d'AIT antérieurs ont montré que des antécédents de vertiges sont un facteur prédictif négatif d'accident vasculaire cérébral ultérieur. Notre objectif était d'évaluer le risque ultérieur d'accident vasculaire cérébral (AVC) dans les 90 jours suivant l'évaluation aux urgences d'un étourdissement isolé diagnostiqué comme un AIT lors de la visite de référence. MéTHODES: Nous avons mené des études de cohorte prospectives multicentriques dans 13 services d'urgence canadiens pendant 11 ans. Nous avons recruté des patients ayant reçu un diagnostic d'AIT et avons comparé les patients présentant des vertiges isolés à ceux présentant d'autres déficits neurologiques. Nous avons inscrit des patients ayant reçu un diagnostic d'AIT et comparé des patients ayant des étourdissements isolés à ceux présentant d'autres déficits neurologiques. Notre résultat primaire était l'AVC subséquent dans les 90 jours. Les résultats secondaires étaient l'AVC subséquent dans les 2, 7 et 30 jours, respectivement, ainsi que l'AIT subséquent dans les 90 jours. RéSULTATS: Seuls 4/483 (0,8 %) des patients présentant des vertiges isolés ont eu un AVC dans les 90 jours, contre 320/11 024 (2,9 %) de ceux présentant un signe ou symptôme neurologique focal (RR 0,29, IC 95 % 0,11-0,76). Au cours des 90 premiers jours, les deux groupes diffèrent significativement en termes de probabilité d'AVC (p = 0,007). L'AIT ultérieur était également significativement moins fréquent dans le groupe des vertiges isolés (1,7 % contre 5,6 %, p = 0,001) avec un risque relatif de 0,30 (IC 95 % 0,15-0,60). CONCLUSIONS: Le risque d'AVC ultérieur après une présentation aux urgences pour un AIT est faible lorsque les symptômes présentés sont des étourdissements isolés.

Vitamin D Supplementation for Benign Paroxysmal Positional Vertigo: A Systematic Review.

OBJECTIVE: Benign paroxysmal positional vertigo (BPPV) is commonly attributed to displaced otoconia. These have been shown to have biomineralization close to that of bone, and vitamin D deficiency has been associated with BPPV. We aim to systematically review the available literature on vitamin D supplementation and BPPV intensity and recurrence in adults. DATABASES REVIEWED: PubMed, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Current Controlled Trials, and ClinicalTrials.gov. METHODS: We systematically reviewed the available literature from 1947 to April 2020. The study protocol was registered in the PROSPERO database (trial registration: CRD42020183195). RESULTS: A total of 179 abstracts were identified and screened by two independent reviewers. Based on inclusion and exclusion criteria, six studies were selected and subjected to a quality assessment. In one randomized clinical trial (RCT), vitamin D supplementation was found to reduce annual recurrence rate of vertigo in patient with BPPV and subnormal serum vitamin D levels compared with placebo (odds ratio, 0.69; 95% confidence interval, 0.54-0.90). Non-RCTs demonstrated the possibility of a null effect in the random effects model (odds ratio, 0.08; 95% confidence interval, 0.00-1.56). The RCT considered as low risk of bias. All of the nonrandomized studies were assessed as serious risk of bias. CONCLUSIONS: The intervention studies identified consistently demonstrated a decrease in BPPV recurrence with supplementation of vitamin D in patients with subnormal vitamin D levels. Although there is a paucity of high-quality studies, the present literature does highlight a role for optimization of vitamin D levels in patients with BPPV.

Clinical Problem Solving: Decreased Level of Consciousness and Unexplained Hydrocephalus.

We present a clinical reasoning case of 42-year-old male with a history of type 1 diabetes who presented to hospital with decreased level of consciousness. We review the approach to coma including initial approach to differential diagnosis and investigations. After refining the diagnostic options based on initial investigations, we review the clinical decision-making process with a focus on narrowing the differential diagnosis, further investigations, and treatment.

Characteristics of persistent postural perceptual dizziness patients in a multidisciplinary dizziness clinic.

BACKGROUND: Persistent Postural Perceptual Dizziness (PPPD) is a newly defined condition which was added to the International Classification of Vestibular Disorders in 2017. Little is known about its impact on patients. OBJECTIVE: The goal of this study was to analyze the symptomology, epidemiology and impact of PPPD on patients. METHODS: A retrospective chart review was done to identify patients who attended the Multidisciplinary Dizziness Clinic (MDC) and were diagnosed with PPPD. Responses to demographic questions, health-related quality of life surveys and several well-validated questionnaires commonly used to assess dizziness severity were analyzed. RESULTS: One hundred patients were diagnosed with PPPD between March 2017 and January 2019, of which 80%(80/100) were females. The average Dizziness Handicap Index score was 60.3±19.0. Responses to the Patient Health Questionnaire classified 53 patients (53/99;53.5%) as moderately to severely depressed. Sixty-four patients (64/100;64.0%) were minimally or mildly anxious according to the Generalized Anxiety Disorder scale. The average Vertigo Symptom Scale score was 24.1/60. The average Situational Vertigo Questionnaire score was 2.00. Forty-nine (49/100;49.0%) patients had migraine symptoms according to the Migraine Screen Questionnaire. CONCLUSIONS: In conclusion, patients with PPPD display important handicap and an elevated risk of depression, anxiety and migraines.

Association between obstructive sleep apnea and persistent postural-perceptual dizziness.

BACKGROUND: Obstructive sleep apnea (OSA) has been linked to vestibular dysfunction, but no prior studies have investigated the relationship between Persistent Postural-Perceptual Dizziness (PPPD), a common cause of chronic dizziness, and OSA. OBJECTIVE AND METHODS: We determined the frequency of OSA in an uncontrolled group of PPPD patients from a tertiary dizziness clinic based on polysomnogram (PSG). We then assessed the sensitivity and specificity of common OSA questionnaires in this population. RESULTS: Twenty-five patients with PPPD underwent PSG (mean age 47, 60% female, mean BMI 29.5). A majority, or 56%, of patients were diagnosed with OSA, and in most, the OSA was severe. OSA patients were older (56 years versus 40 years, p = 0.0006) and had higher BMI (32 versus 26, p = 0.0078), but there was no clear gender bias (56% versus 64% female, p = 1.00). The mean sensitivity and specificity of the STOP BANG questionnaire for detecting OSA was 86% and 55%, respectively. Sensitivity and specificity of the Berlin Questionnaire was 79% and 45%, respectively. CONCLUSIONS: The prevalence of OSA was much higher in our small PPPD group than in the general population. Screening questionnaires appear to demonstrate good sensitivity to detect PPPD patients at risk of OSA in this small study. Future studies should confirm these findings and determine whether treatment of OSA improves symptoms in PPPD.

Limited usefulness of routine head and neck CT angiogram in the imaging assessment of dizziness in the emergency department.

OBJECTIVE: To assess the usefulness of head and neck computed tomography angiogram for the investigation of isolated dizziness in the emergency department in detecting significant acute findings leading to a change in management in comparison to non-contrast computed tomography scan of the head. METHODS: Patients presenting with isolated dizziness in the emergency department investigated with non-contrast computed tomography and computed tomography angiogram over the span of 36 months were included. Findings on non-contrast computed tomography were classified as related to the emergency department presentation versus unrelated/no significant abnormality. Similarly, computed tomography angiogram scans were classified as positive or negative posterior circulation findings. RESULTS: One hundred and fifty-three patients were imaged as a result of emergency department presentation with isolated dizziness. Fourteen cases were diagnosed clinically as of central aetiology. Non-contrast computed tomography was positive in three patients, all with central causes with sensitivity 21.4%, specificity 100%, positive predictive value 100%, negative predictive value 92.6% and accuracy 92.8%. Computed tomography angiogram was positive for angiographic posterior circulation abnormalities in five cases, and only two of them had a central cause of dizziness, with sensitivity 14.3%, specificity 97.7%, positive predictive value 40%, negative predictive value 91.46% and accuracy 92.1%. CONCLUSION: Both non-contrast computed tomography and computed tomography angiogram of the head and neck have low diagnostic yield for the detection of central causes of dizziness, However, non-contrast computed tomography has higher sensitivity and positive predictive value than computed tomography angiogram, implying a lack of diagnostic advantage from the routine use of computed tomography angiogram in the emergency department for the investigation of isolated dizziness. Further studies are required to determine the role of computed tomography angiogram in the work-up of isolated dizziness in the emergency department.

A retrospective analysis of two tertiary care dizziness clinics: a multidisciplinary chronic dizziness clinic and an acute dizziness clinic.

BACKGROUND: Vertigo remains a diagnostic challenge for primary care, emergency, and specialist physicians. Multidisciplinary clinics are increasingly being employed to diagnose and manage patients with dizziness. We describe, for the first time in Canada, the clinical characteristics of patients presenting with chronic and acute dizziness to both a multidisciplinary chronic dizziness clinic (MDC) and a rapid access dizziness (RAD) clinic at The Ottawa Hospital (TOH). METHODS: We performed a retrospective review of all patients presenting to the MDC and RAD clinics at TOH from July 2015 to August 2017. RESULTS: Overall, 211 patients (median age: 61 years old) presented to the RAD clinic and 292 patients (median age: 55 years old) presented to the MDC. In the RAD clinic, 63% of patients had peripheral dizziness, of which 55% had BPPV, and only one patient had functional dizziness. Interestingly, only 25% of RAD diagnoses were concordant with emergency department diagnoses; moreover, only 33% of RAD patients had HiNTS completed, while 44% had CT scans, of which only one scan had an abnormal finding. Prior to assessment, all patients in the MDC had an unclear cause of dizziness. 28% of patients had vestibular dizziness and 21% had functional dizziness, of which 43% had persistent postural perceptual dizziness. Moreover, 12% of patients with functional dizziness also suffered from comorbid severe anxiety and depression. CONCLUSIONS: Dizziness is a heterogeneous disorder that necessitates multidisciplinary care, and clinics targeting both the acute and chronic setting can improve diagnostic accuracy, ensure appropriate diagnostic testing, and facilitate effective care plans for patients with dizziness.

Dizziness at a Canadian tertiary care hospital: a cost-of-illness study.

BACKGROUND: In the Canadian health care system, determining overall costs associated with a particular diagnostic subgroup of patients, in this case dizzy patients, is the first step in the process of determining where costs could be saved without compromising patient care. This study is the first Canadian study that evaluates these costs at a tertiary care hospital and will allow for the extrapolation of cost data for other similar academic health science centers, regional health initiatives, and provincial healthcare planning structures. METHODS: We conducted a retrospective cohort study of patients of any age presenting to The Ottawa Hospital (TOH), a tertiary care hospital, between January 1st, 2009 and December 31st, 2014 with a main diagnosis of dizziness or dizziness-related disease. De-identified patient information was acquired through TOH Data Warehouse and included a patient's sex, age, arrival and departure dates, Elixhauser co-morbidity score, location of presentation (emergency department or admitted inpatient) presenting complaint, final diagnosis code, any procedure codes linked to their care, and the direct and indirect hospital costs linked with any admission. We derived the mean hospital costs and 95% confidence interval for each diagnosis. We obtained the number of patients who were diagnosed with dizziness within Ontario in year 2015-16 from Canadian Institute for Health Information (CIHI). A simple frequency multiplication was performed to estimate the total cost burden for Ontario based on the cost estimate for the same year obtained from TOH. Cost data were presented in 2017 Canadian dollars. RESULTS: The average total hospital cost per patient with dizziness for the entire cohort is $450 (SD = $1334), with ED only patients costing $359 (SD = $214). The total estimated hospital cost burden of dizziness in Ontario is $31,202,000 (95% CI $29,559,000 - 32,844,000). CONCLUSIONS: The estimated annual costs of emergency department ambulatory and inpatient dizziness in Ontario was calculated to be approximately 31 million dollars per year. This is the first step in identifying potential areas for cost savings to aid local and provincial policy-makers in allocation of health care spending.

Novel Use of Portable Audiometry to Track Hearing Fluctuations in Menière's Disease: A Pilot Study.

INTRODUCTION: Menière's Disease (MD) is a disorder of the inner ear consisting of episodic attacks of vertigo associated with aural fullness, tinnitus, and fluctuating hearing loss. Hearing levels in MD can often fluctuate over time, and may eventually decline permanently in a step-wise fashion. There are no current studies examining daily hearing fluctuations for prolonged periods in patients with MD. Portable audiometry has the potential to allow the patient to monitor their hearing on a daily basis without attending a center for formal audiology. The objective of this pilot study was to assess feasibility of using iPad-based audiometry on a daily basis to capture hearing fluctuations in a small sample of adult patients with active MD. METHODS: We recruited five patients with active MD as defined by current diagnostic criteria (International Classification of Vestibular Disease 2015). "Active" MD was defined as the patient having had at least one typical Menière's episode within the last 4 weeks. Patients were trained on how to use the portable audiometer and asked to perform at least daily audiograms for 3 months. Patients were asked to manually track vertigo attacks in a diary. Qualitative feedback was obtained from each patient at each monthly visit. For each patient, individual pure tone thresholds at each frequency and pure-tone averages (PTA) were analyzed for maximum and minimum values and interquartile ranges. RESULTS: There were four women and one man, with an average age of 49.8 years. Duration of MD ranged from 4 months to 5 years. None of the patients experienced any technical difficulties performing the testing at home. The average duration of each test was 4.2 minutes, with the longest test taking 19.2 minutes. Patients completed between 45 and 102 tests, with an average of 72. The interquartile range for the PTA ranged from 2.5 to 25 dB for affected ears, and 0 to 6.25 dB for unaffected ears with maximums ranging from 5 to 35 dB in affected ears, and 0 to 10 dB in unaffected ears. CONCLUSIONS: Daily portable audiometry is feasible in patients with MD. Future studies are planned to further analyze hearing fluctuations in MD with respect to frequencies affected, relationship to vertigo attacks, and response to treatments. Understanding hearing fluctuations in MD may aid refinement of diagnostic criteria and improve prognostication for long-term hearing loss, with a goal of informing treatments that might improve final hearing outcome.

Usage of the HINTS exam and neuroimaging in the assessment of peripheral vertigo in the emergency department.

BACKGROUND: Dizziness is a common presenting symptom in the emergency department (ED). The HINTS exam, a battery of bedside clinical tests, has been shown to have greater sensitivity than neuroimaging in ruling out stroke in patients presenting with acute vertigo. The present study sought to assess practice patterns in the assessment of patients in the ED with peripherally-originating vertigo with respect to utilization of HINTS and neuroimaging. METHODS: A retrospective cohort study was performed using data pertaining to 500 randomly selected ED visits at a tertiary care centre with a final diagnostic code related to peripherally-originating vertigo between January 1, 2010 - December 31, 2014. RESULTS: A total of 380 patients met inclusion criteria. Of patients presenting to the ED with dizziness and vertigo and a final diagnosis of non-central vertigo, 139 (36.6%) received neuroimaging in the form of CT, CT angiography, or MRI. Of patients who did not undergo neuroimaging, 17 (7.1%) had a bedside HINTS exam performed. Almost half (44%) of documented HINTS interpretations consisted of the ambiguous usage of "HINTS negative" as opposed to the terminology suggested in the literature ("HINTS central" or "HINTS peripheral"). CONCLUSIONS: In this single-centre retrospective review, we have demonstrated that the HINTS exam is under-utilized in the ED as compared to neuroimaging in the assessment of patients with peripheral vertigo. This finding suggests that there is room for improvement in ED physicians' application and interpretation of the HINTS exam.

Recessive mutations in ATP8A2 cause severe hypotonia, cognitive impairment, hyperkinetic movement disorders and progressive optic atrophy.

BACKGROUND: ATP8A2 mutations have recently been described in several patients with severe, early-onset hypotonia and cognitive impairment. The aim of our study was to characterize the clinical phenotype of patients with ATP8A2 mutations. METHODS: An observational study was conducted at multiple diagnostic centres. Clinical data is presented from 9 unreported and 2 previously reported patients with ATP8A2 mutations. We compare their features with 3 additional patients that have been previously reported in the medical literature. RESULTS: Eleven patients with biallelic ATP8A2 mutations were identified, with a mean age of 9.4 years (range 2.5-28 years). All patients with ATP8A2 mutations (100%) demonstrated developmental delay, severe hypotonia and movement disorders, specifically chorea or choreoathetosis (100%), dystonia (27%) and facial dyskinesia (18%). Optic atrophy was observed in 78% of patients for whom funduscopic examination was performed. Symptom onset in all (100%) was noted before 6 months of age, with 70% having symptoms noted at birth. Feeding difficulties were common (91%) although most patients were able to tolerate pureed or thickened feeds, and 3 patients required gastrostomy tube insertion. MRI of the brain was normal in 50% of the patients. A smaller proportion was noted to have mild cortical atrophy (30%), delayed myelination (20%) and/or hypoplastic optic nerves (20%). Functional studies were performed on differentiated induced pluripotent cells from one child, which confirmed a decrease in ATP8A2 expression compared to control cells. CONCLUSIONS: ATP8A2 gene mutations have emerged as the cause of a novel neurological phenotype characterized by global developmental delays, severe hypotonia and hyperkinetic movement disorders, the latter being an important distinguishing feature. Optic atrophy is common and may only become apparent in the first few years of life, necessitating repeat ophthalmologic evaluation in older children. Early recognition of the cardinal features of this condition will facilitate diagnosis of this complex neurologic disorder.