Pearls & Oy-sters: Ocular Myasthenia Gravis: Central Ocular Motor Signs and Unilateral Visual Loss Caused by the Great Neuro-Ophthalmologic Impersonator.

Myasthenia gravis (MG) has been described as a great mimicker of other neurologic and ocular motility disorders, including centrally mediated ophthalmoplegia. For example, ocular myasthenia gravis (ocular MG) may cause impaired binocular visual acuity for near vision due to reduced accommodation or for distance vision due to accommodative excess. Notably, accommodative excess due to ocular MG is rare, but may occur with exotropia, with or without diplopia. We report 2 cases of ocular MG: First, a 32-year-old man with exotropia, bilateral hypometric and slowed adducting saccades with dissociated abducting nystagmus, miosis, and decreased distance vision in his right eye; second, a 45-year-old man with similar ocular motor deficits, miosis, and myopia. Both patients showed ocular motor deficits which appeared to localize to the pons but were instead due to ocular MG. Ocular MG should be considered in patients who present with reduced visual acuities due to any disruption in accommodation. Any ocular motor deficit, even if appearing to be centrally mediated or occurring without ptosis, may be caused by ocular MG.

James Sharpe's Contributions to Neurology and Neuro-ophthalmology: A Posthumous Tribute 10 Years On.

Dr. Sharpe was a leading eye movement researcher who had also been the editor of this journal. We wish to mark the 10th anniversary of his death by providing a sense of what he had achieved through some examples of his research.

The relationship of cervicothoracic mobility restrictions to fall risk and fear of falling in ankylosing spondylitis.

Objective: The objective of this study is to determine whether restricted cervical mobility in ankylosing spondylitis (AS) is associated with increased fall frequency or fear of falling. Methods: A total of 134 AS patients and 199 age- and gender-matched control subjects (CS) with soft-tissue cervicothoracic pain were prospectively evaluated for fall risk. Subjects were divided into non-fallers, single fallers, and multiple fallers. Dynamic cervical rotations and static cervicothoracic axial measurements were compared between the groups. In total, 88 AS patients were reviewed more than once; Kaplan-Meier plots were constructed for fall risk as a function of cervical rotation amplitudes. Falls Efficacy Scale-International (FES-I) questionnaire measured the fear of falling. Results: In total, 34% of AS patients and 29% of CS fell (p = 0.271) in the year prior to evaluation. In AS, static anatomical measurements were unrelated to fall occurrence. The trends of multiple AS fallers to greater flexed forward postures and reduced dynamic cervical rotations were not statistically significant. Cervicothoracic pain (p = 0.0459), BASDAI (p = 0.002), and BASFI (p = 0.003) scores were greater in multiple fallers. FES-I scores were greater in fallers (p = 0.004). Of the 88 AS patients reviewed (or seen) on more than one occasion, 46.5% fell over the 9-year observation period, including all multiple fallers and 71.4% of single fallers. Survival curves showed increased fall risk as cervical rotational amplitudes decreased. Conclusion: In AS, decreased cervical rotations increase fall risk and fear of falling. In multiple fallers, falls were associated with greater disease activity. Cervical muscle stiffness in AS may cause non-veridical proprioceptive inputs and contribute to increased fall frequency similar to individuals with soft-tissue cervicothoracic pain.

A novel WFS1 variant associated with isolated congenital cataracts.

Biallelic variants in the WFS1 gene are associated with Wolfram syndrome. However, recent publications document that heterozygous variants can lead to a variety of phenotypes, such as Wolfram-like syndrome or isolated features of Wolfram syndrome. In this case report, we present a male patient with a history of congenital cataracts and subjective complaints of muscle weakness. Clinical assessment demonstrated normal muscle strength, and genomic, biochemical, electrophysiologic, and muscle biopsy studies did not identify a potential cause of the proband's perceived muscle weakness. Whole-exome sequencing identified a novel de novo variant in the WFS1 gene (c.1243G > T), representing one of only several patients in the published literature with isolated congenital cataracts and a heterozygous WFS1 variant. The variety of phenotypes associated with heterozygous variants in WFS1 suggests that this gene should be considered as a cause of both dominant and biallelic/recessive forms of disease. Future research should focus on elucidating the mechanism(s) of disease and variable expressivity in WFS1 in order to improve our ability to provide patients and families with anticipatory guidance about the disease, including appropriate screening and medical interventions.

Cervicothoracic Mechanical Impairment as Part of Complete Neurological Fall Risk Appraisal.

BACKGROUND: Assessment of individuals at risk for falling entails comprehensive neurological and vestibular examinations. Chronic limitation in cervical mobility reduces gaze accuracy, potentially impairing navigation through complex visual environments. Additionally, humans with scoliosis have altered otolithic vestibular responses, causing imbalance. We sought to determine whether dynamic cervical mobility restrictions or static cervicothoracic impairments are also fall risk factors. METHODS: We examined 435 patients referred for soft-tissue musculoskeletal complaints; 376 met criteria for inclusion (mean age 52; 266 women). Patients were divided into nonfallers, single fallers, and multiple fallers, less or greater than 65 years old. Subject characteristics, dynamic cervical rotations, and static cervicothoracic axial measurements were compared between groups. Fear of falling was evaluated using the Falls Efficacy Scale-International questionnaire. RESULTS: Long-standing cervicothoracic pain and stiffness conferred increased risk of falling. Neck rotation amplitudes decreased with longer duration musculoskeletal symptoms and were significantly more restricted in fallers, doubling the risk of falling and contributing to increased fear of falling. Mid-thoracic scoliosis amplitudes increased over time, but static axial abnormalities were not greater among fallers, although thoracic kyphoscoliosis heightened fear of falling. CONCLUSION: In patients at fall risk, thoracic kyphoscoliosis and dynamic neck movements should be assessed, in addition to standard vestibular and neurological evaluations. Additionally, patients with soft tissue cervicothoracic pain and restricted mobility have increased fall frequency and fear of falling, independent of other fall risk factors and should undergo complete fall risk appraisal.

Mass Spectrometry Evaluation of Biomarkers in the Vitreous Fluid in Gaucher Disease Type 3 with Disease Progression Despite Long-Term Treatment.

Intraocular lesions have been infrequently reported in patients with Gaucher disease type 3 (GD3). We previously reported siblings with GD3 who responded well to the combination of enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). Here we report progressive bilateral vitreous and preretinal deposits with declining visual acuity requiring bilateral vitrectomies in one of these siblings. These ocular manifestations had progressed despite combined ERT and SRT with improvement in visual acuity after vitrectomies. Vitrectomy fluid analysis performed for the first time by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) identified a high concentration of glucosylceramide (GluCer) in the patient (262.842 nM) compared to a sample (0.428 nM from a patient without a lysosomal storage or known hereditary metabolic disorder). The GluCer detected in our patient was resolved into 12 different isoforms including two methylated ones. No evidence of galactosylceramide (GalCer) was detected. The development of these intraocular manifestations and their characterization by UPLC-MS/MS indicate a need for ongoing ophthalmologic evaluation of all GD patients and for new therapies that can cross the blood-retinal and blood-brain barriers for patients with GD and other neuropathic lysosomal storage disorders.

Inaccurate Saccades and Enhanced Vestibulo-Ocular Reflex Suppression during Combined Eye-Head Movements in Patients with Chronic Neck Pain: Possible Implications for Cervical Vertigo.

BACKGROUND: The primate ocular motor system is designed to acquire peripheral targets of interest by coordinating visual, vestibular, and neck muscle activation signals. The vestibulo-ocular reflex (VOR) is greatly reduced at the onset of large eye-head (gaze) saccades and resumes before the end of the saccades to stabilize eye-in-orbit and ensure accurate target acquisition. Previous studies have relied on manipulating head movements in normal individuals to study VOR suppression and gaze kinematics. We sought to determine if reduced head-on-trunk movement alters VOR suppression and gaze accuracy similar to experiments involving normal subjects and if intentionally increasing head and neck movement affects these dynamics. METHODS: We measured head and gaze movements using magnetic search coil oculography in eight patients with cervical soft tissue disorders and seven healthy subjects. All participants made horizontal head-free saccades to acquire a laser dot target that stepped pseudorandomly 30-65° to either side of orbital mid-position, first using typical head and eye movements and again after being instructed to increase head amplitudes as much as possible. RESULTS: Compared to healthy subjects, patients made smaller head movements that contributed only 6% to total gaze saccade amplitudes. Head movements were also slowed, prolonged, and delayed. VOR suppression was increased and prolonged. Gaze saccades were inaccurate and delayed with long durations and decreased peak velocities. CONCLUSION: In patients with chronic neck pain, the internal commands issued for combined eye-head movements have large enough amplitudes to create accurate gaze saccades; however, because of increased neck stiffness and viscosity, the head movements produced are smaller, slower, longer, and more delayed than they should be. VOR suppression is disproportionate to the size of the actual gaze saccades because sensory feedback signals from neck proprioceptors are non-veridical, likely due to prolonged coactivation of cervical muscles. The outcome of these changes in eye-head kinematics is head-on-trunk stability at the expense of gaze accuracy. In the absence of vestibular loss, the practical consequences may be dizziness (cervical vertigo) in the short term and imbalance and falls in the long term.

Migraine with Aura or Sports-Related Concussion: Case Report, Pathophysiology, and Multidisciplinary Approach to Management.

The evaluation and management of athletes presenting with clinical features of migraine headache with aura in the setting of sports-related head trauma is challenging. We present a case report of a 15-yr-old boy with a history of migraine with visual aura that developed acute visual disturbance and headache after a head injury during an ice hockey game. The patient underwent comprehensive assessment at a multidisciplinary concussion program, including neuro-ophthalmological examination, neurocognitive testing, and graded aerobic treadmill testing. Clinical history and multidisciplinary assessment was consistent with the diagnosis of coexisting sports-related concussion and migraine with brainstem aura. The authors discuss the pearls and pitfalls of managing patients who develop migraine headache with visual aura after sports-related head injury and the value of a comprehensive multidisciplinary approach to this unique patient population.

Recurrent Ataxia in Children and Adolescents.

BACKGROUND: Recurrent ataxia is encountered infrequently in clinical pediatric neurology practise and presents with diagnostic challenges. It is caused by several disorders. Our aims were to describe the epidemiology and clinical features in children with recurrent ataxia. MATERIALS AND METHODS: A retrospective review was undertaken in 185 children with chronic ataxia, who presented during 1991 to 2008. Several databases were searched to ensure optimum ascertainment. Patients with brain tumors or isolated disorders of the peripheral nerves or vestibular system were excluded. RESULTS: Recurrent ataxia was reported in 21 patients. Their age range was between 6 and 32.75 years (males=12). The crude period prevalence rate for the 18-year study period was 7.44/100,000. Eight patients had episodic ataxia and seven had inflammatory and metabolic disorders. In the rest the etiology was unknown. Many patients presented with ataxia, dizziness, and vertigo. The frequency and duration of the ataxic episodes varied from several per day to one every few months. Other clinical features included developmental delay and seizures. Neuroimaging in episodic ataxia was normal and abnormal in inflammatory or metabolic disorders. Acetazolamide provided symptomatic relief in patients with episodic ataxia, while steroids were beneficial in patients with an inflammatory etiology. One child with a metabolic disorder died. CONCLUSIONS: Recurrent ataxia is an uncommon presentation in children and mortality is rare. Genetic, metabolic, and inflammatory disorders should be considered in these patients. Neuroimaging is essential. Acetazolamide in selected patients provides good symptomatic relief.

Multidisciplinary Management of Pediatric Sports-Related Concussion.

OBJECTIVES: To summarize the clinical characteristics and outcomes of pediatric sports-related concussion (SRC) patients who were evaluated and managed at a multidisciplinary pediatric concussion program and examine the healthcare resources and personnel required to meet the needs of this patient population. METHODS: We conducted a retrospective review of all pediatric SRC patients referred to the Pan Am Concussion Program from September 1st, 2013 to May 25th, 2015. Initial assessments and diagnoses were carried out by a single neurosurgeon. Return-to-Play decision-making was carried out by the multidisciplinary team. RESULTS: 604 patients, including 423 pediatric SRC patients were evaluated at the Pan Am Concussion Program during the study period. The mean age of study patients was 14.30 years (SD: 2.32, range 7-19 years); 252 (59.57%) were males. Hockey (182; 43.03%) and soccer (60; 14.18%) were the most commonly played sports at the time of injury. Overall, 294 (69.50%) of SRC patients met the clinical criteria for concussion recovery, while 75 (17.73%) were lost to follow-up, and 53 (12.53%) remained in active treatment at the end of the study period. The median duration of symptoms among the 261 acute SRC patients with complete follow-up was 23 days (IQR: 15, 36). Overall, 25.30% of pediatric SRC patients underwent at least one diagnostic imaging test and 32.62% received referral to another member of our multidisciplinary clinical team. CONCLUSION: Comprehensive care of pediatric SRC patients requires access to appropriate diagnostic resources and the multidisciplinary collaboration of experts with national and provincially-recognized training in TBI.

Large Genomic Deletions in CACNA1A Cause Episodic Ataxia Type 2.

Episodic ataxia (EA) syndromes are heritable diseases characterized by dramatic episodes of imbalance and incoordination. EA type 2 (EA2), the most common and the best characterized subtype, is caused by mostly nonsense, splice site, small indel, and sometimes missense mutations in CACNA1A. Direct sequencing of CACNA1A fails to identify mutations in some patients with EA2-like features, possibly due to incomplete interrogation of CACNA1A or defects in other EA genes not yet defined. Previous reports described genomic deletions between 4 and 40 kb in EA2. In 47 subjects with EA (26 with EA2-like features) who tested negative for mutations in the known EA genes, we used multiplex ligation-dependent probe amplification to analyze CACNA1A for exonic copy number variations. Breakpoints were further defined by long-range PCR. We identified distinct multi-exonic deletions in three probands with classic EA2-like features: episodes of prolonged vertigo and ataxia triggered by stress and fatigue, interictal nystagmus, with onset during infancy or early childhood. The breakpoints in all three probands are located in Alu sequences, indicating errors in homologous recombination of Alu sequences as the underlying mechanism. The smallest deletion spanned exons 39 and 40, while the largest deletion spanned 200 kb, missing all but the first three exons. One deletion involving exons 39 through 47 arose spontaneously. The search for mutations in CACNA1A appears most fruitful in EA patients with interictal nystagmus and onset early in life. The finding of large heterozygous deletions suggests haploinsufficiency as a possible pathomechanism of EA2.

Parasellar syndromes.

The parasellar compartments are located lateral to and on either side of the sella turcica. The cavernous sinuses are the most prominent anatomic feature of the parasella. Each sinus consists of a plexus of veins through which runs the intracavernous portion of the internal carotid artery. Ocular motor nerves three and four travel within the dural covering of the cavernous sinus to the superior orbital fissure, and cranial nerve six travels through the carotid sinus itself, giving rise to parasellar syndromes, which have distinctive clinical features. Ophthalmoplegia occurs as a result of damage to these ocular motor nerves and variable involvement of oculosympathetic nerves. Facial pain, dysesthesia, and paraesthesia are caused by damage to one or more of the divisions of the fifth cranial nerve, travelling in the dural wall of the cavernous sinus. Tumors, such as meningiomas, frequently cause parasellar syndromes, as do aneurysms of the intracavernous portion of the internal carotid artery, carotid-cavernous fistulas, and cavernous sinus thrombosis. Inflammatory conditions such as Tolosa-Hunt syndrome, ischemia to small vessels supplying the cavernous portion of the cranial nerves, and infections can cause this syndrome. Magnetic resonance imaging is the investigation of choice and therapy is specific to the cause of the parasellar syndrome, but now includes more aggressive endoscopic and microsurgical intervention, and radiosurgery.