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Background and ObjectivesLesions of the cerebellar flocculus cause enduring downbeat nystagmus (DBN) with unrelenting oscillopsia. Unlike most patients with DBN, the flocculus is structurally spared in nonalcoholic Wernicke encephalopathy (nWE) with chronic DBN. The objective was to study the effects of alcohol in nWE.MethodsWe recorded eye movements of a unique patient with nWE under controlled alcohol consumption who said his oscillopsia disappeared with a few drinks of alcohol.ResultsHis DBN was markedly diminished by alcohol (by 77.4%), although he remained alert with normal saccades.DiscussionThis striking observation may be caused by the differential effect of alcohol on the perihypoglossal complex and the paramedian tract neurons, which control the level of activity in the flocculus, with opposite (inhibition and excitation, respectively) effects. The finding suggests new ideas about the treatment and pathophysiology of DBN with a structurally intact cerebellum.

Objective Gaze‐evoked nystagmus (GEN) is a central sign in patients with the acute vestibular syndrome (AVS); however, discriminating between a pathological and a physiologic GEN is a challenge. Here we evaluate GEN in patients with AVS. Methods In this prospective cross‐sectional study, we used video‐oculography (VOG) to compare GEN in the light (target at 15° eccentric) in 64 healthy subjects with 47 patients seen in the emergency department (ED) who had AVS; 35 with vestibular neuritis and 12 with stroke. All patients with an initial non‐diagnostic MRI received a confirmatory, delayed MRI as a reference standard in detecting stroke. Results Healthy subjects with GEN had a time constant of centripetal drift >18 s. VOG identified pathologic GEN (time constant ≤ 18 s) in 33% of patients with vestibular strokes, specificity was 100%, accuracy was 83%. Results were equivalent to examination by a clinical expert. As expected, since all patients with GEN had a SN in straight‐ahead position, they showed the pattern of a Bruns’ nystagmus. Conclusions One third of patients with AVS due to central vestibular strokes had a spontaneous SN in straight‐ahead gaze and a pathological GEN, producing the pattern of a Bruns’ nystagmus with a shift of the null position. The localization of the side of the lesion based on the null was not consistent, presumably because the circuits underlying gaze‐holding are widespread in the brainstem and cerebellum. Nevertheless, automated quantification of GEN with VOG was specific, and accurately identified patients in the ED with AVS due to strokes., One third of patients with an acute vestibular syndrome due to central vestibular strokes had a spontaneous nystagmus in straight‐ahead gaze and a pathological gaze‐evoked nystagmus, producing the pattern of a Bruns’ nystagmus with a shift of the null position.

Fatal familial insomnia (FFI) is a rare inherited prion disease characterized by sleep, autonomic, and motor disturbances. Neuro-ophthalmological abnormalities have been reported at the onset of disease, although not further characterized. We analyzed video recordings of eye movements of 6 patients with FFI from 3 unrelated kindreds, seen within 6 months from the onset of illness. Excessive saccadic intrusions were the most prominent findings. In patients with severe insomnia, striking saccadic intrusions are an early diagnostic clue for FFI. The fact that the thalamus is the first structure affected in FFI also suggests its role in the control of steady fixation. ANN NEUROL 2021;89:823–827.

Ocular lateral deviation (OLD) is a conjugate, ipsilesional, horizontal ocular deviation associated with brief (3-5 s) closing of the eyes, commonly linked to the lateral medullary syndrome (LMS). There is limited information regarding OLD in patients with the acute vestibular syndrome (AVS). In one case series 40 years ago OLD was suggested to be a central sign. Recently, horizontal ocular deviation on imaging (RadOLD) was frequently associated with anterior circulation stroke and horizontal gaze palsy. Similarly, RadOLD has been associated with posterior circulation stroke, e.g., LMS and cerebellar stroke, but without clinical correlation with OLD.This is a prospective, cross-sectional diagnostic study of 151 acute AVS patients. Patients had spontaneous nystagmus. Horizontal gaze paralysis was an exclusion criterion. We noted the effect of brief 3-5 s eyelid closure on eye position, and then used the HINTS algorithm (the head-impulse test, nystagmus characteristics and skew deviation) and RadOLD, to establish a correlation between clinical and radiologic findings RESULTS: Of the 151 AVS patients, 100 had a central lesion and 51 a peripheral lesion; 29 of the central lesions were LMS, and 11 had OLD. Additionally, one lateral pontine syndrome had OLD. On opening the eyes 11 patients with OLD and LMS made multiple, hypometric corrective saccades to bring gaze back to straight ahead. 10/11 patients with LMS showed RadOLD.OLD with multiple hypometric corrective saccades on opening the eyes was infrequent but highly localizing and lateralizing. We emphasize how simple it is to test for OLD, with the caveat that to be specific, it must be present after just brief (3-5 s) eyelid closure.

Introduction Benign paroxysmal positional vertigo (BPPV) of the horizontal semicircular canal (hSCC) can present with otoconia blocking its lumen (canalith jam), with signs and symptoms that make it difficult to distinguish from central nervous system pathology. Objective Here we report two cases of canalith jam affecting the hSCC and offer a theoretical mechanism based on known vestibular neurophysiology. Methods We use video‐oculography to document the canalith jam and show the moment the otoconia loosen. Results Canalith jam is a rare form of BPPV remedied with repositioning maneuvers. Conclusion Clinicians should consider canalith jam as a mechanism for BPPV when the nystagmus is (a) Direction fixed with fixation removed and during positional testing; (b) Velocity dependent on supine head position; (c) Converts to geotropic directional changing nystagmus.

Patients with acute vestibular disorders are often a diagnostic challenge for neurologists, especially when the evaluation must be conducted remotely. The clinical dilemma remains: Does the patient have a benign peripheral inner ear problem or a worrisome central vestibular disorder, such as a stroke? The use of a focused history and the virtual HINTS (head impulse test, nystagmus evaluation, and test of skew) examination are key steps towards correctly diagnosing and triaging the acute vertiginous patient. When looking for signs of vestibulo-ocular dysfunction, there are important technological and practical considerations for an effective clinical interpretation.

Inborn errors of metabolism in adults are still largely unexplored. Despite the fact that adult-onset phenotypes have been known for many years, little attention is given to these disorders in neurological practice. The adult-onset presentation differs from childhood-onset phenotypes, often leading to considerable diagnostic delay. The identification of these patients at the earliest stage of disease is important, given that early treatment may prevent or lessen further brain damage. Neurological and psychiatric symptoms occur more frequently in adult forms. Abnormalities of eye movements are also common and can be the presenting sign. Eye movement disorders can be classified as central or peripheral. Central forms are frequently observed in lysosomal storage disorders, whereas peripheral forms are a key feature of mitochondrial disease. Furthermore, oculogyric crisis is an important feature in disorders affecting dopamine syntheses or transport. Ocular motor disorders are often not reported by the patient, and abnormalities can be easily overlooked in a general examination. In adults with unexplained psychiatric and neurological symptoms, a special focus on examination of eye movements can serve as a relatively simple clinical tool to detect a metabolic disorder. Eye movements can be easily quantified and analyzed with video-oculography, making them a valuable biomarker for following the natural course of disease or the response to therapies. Here, we review, for the first time, eye movement disorders that can occur in inborn errors of metabolism, with a focus on late-onset forms. We provide a step-by-step overview that will help clinicians to examine and interpret eye movement disorders. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Benign paroxysmal positional vertigo (BPPV) is common, sometimes terrifying, but rarely portends serious disease. It is usually easily diagnosed and treated, and both the patient and the physician are immediately gratified. While much has been learned about the pathogenesis of BPPV in the past decades, many of its features remain mysterious, and one must still be wary of the rare times it mimics a dangerous brain disorder. Here we review common, relatively well understood clinical features of BPPV but also emphasize what we do not know and when the physician must look deeper for a more ominous cause.

Purpose of review In the last three decades, the use of eye movements and vestibular testing in many neurological disorders has accelerated, primarily because of practical technologic developments. Although the acute vestibular syndrome is a prime example of this progress, more chronic neurologic and systemic disorders have received less attention. We focus here on recent contributions relating vestibular and ocular motor abnormalities in inflammatory, demyelinating, metabolic, and peripheral nervous system disorders RECENT FINDINGS: Vestibular abnormalities have been identified in acute demyelinating neuropathies (AIDP), in novel genetic mutations responsible for CANVAS (cerebellar ataxia, neuropathy vestibular areflexia syndrome), and in other inherited neuropathies (variants of Charcot-Marie-Tooth disease). In addition, there are differentiating characteristics between the most common CNS demyelinating disorders: multiple sclerosis and neuromyelitis optica (NMO). We summarize new information on Vitamin D metabolism in benign paroxysmal positional vertigo (BPPV), followed by a brief review of the vestibular and ocular motor findings in Wernicke's encephalopathy. We conclude with findings in several paraneoplastic/autoimmune disorders. Summary This literature review highlights the impact of a careful vestibular and ocular motor evaluation in common neurologic disorder, not only for the initial diagnosis but also for monitoring disease and rehabilitation. A careful examination of eye movements and vestibular function, supplemented with new video techniques to quantify the findings, should be part of the standard neurologic examination.

Patients with Wernicke's encephalopathy (WE) often have unusual patterns of vertical nystagmus. Initially there is often a spontaneous upbeating nystagmus that may change to downbeat nystagmus with a change in the direction of gaze, convergence or with vestibular stimuli. Patients also often show a profound loss of the horizontal but not the vertical vestibulo-ocular reflex (VOR). Furthermore, the acute upbeat nystagmus may change to a chronic downbeat nystagmus. We present hypotheses for these features based on (1) the location of vertical gaze-holding networks near the area postrema of the dorsomedial medulla where the blood-brain barrier is located, which we suggest becomes compromised in WE, (2) the location of the vestibular nuclei in the brainstem, medially for the horizontal VOR, and laterally for the vertical VOR, (3) neuronal circuits differ in susceptibility to and in the ability to recover from thiamine deficiency, and (4) impaired processing of otolith information in WE, normally used to modulate translational vestibulo-ocular reflexes, leads to some of the characteristics of the spontaneous vertical nystagmus including the peculiar reversal in its direction with a change in gaze or convergence.

Ocular motor neural integrators ensure that eyes are held steady in straight-ahead and eccentric positions of gaze. Abnormal function of the ocular motor neural integrator leads to centripetal drifts of the eyes with consequent gaze-evoked nystagmus. In 2002 a neural integrator, analogous to that in the ocular motor system, was proposed for the control of head movements. Recently, a counterpart of gaze-evoked eye nystagmus was identified for head movements; in which the head could not be held steady in eccentric positions on the trunk. These findings lead to a novel pathophysiological explanation in cervical dystonia, which proposed that the abnormalities of head movements stem from a malfunctioning head neural integrator, either intrinsically or as a result of impaired cerebellar, basal ganglia, or peripheral feedback. Here we briefly recapitulate the history of the neural integrator for eye movements, then further develop the idea of a neural integrator for head movements, and finally discuss its putative role in cervical dystonia. We hypothesize that changing the activity in an impaired head neural integrator, by modulating feedback, could treat dystonia. * Abbreviation : INC : interstitial nucleus of Cajal

Biallelic pathogenic variants in AARS2, a gene encoding the mitochondrial alanyl-tRNA synthetase, result in a spectrum of findings ranging from infantile cardiomyopathy to adult-onset progressive leukoencephalopathy. In this article, we present three unrelated individuals with novel compound heterozygous pathogenic AARS2 variants underlying diverse clinical presentations. Patient 1 is a 51-year-old man with adult-onset progressive cognitive, psychiatric, and motor decline and leukodystrophy. Patient 2 is a 34-year-old man with childhood-onset progressive tremor followed by the development of polyneuropathy, ataxia, and mild cognitive and psychiatric decline without leukodystrophy on imaging. Patient 3 is a 57-year-old woman with childhood-onset tremor and nystagmus which preceded dystonia, chorea, ataxia, depression, and cognitive decline marked by cerebellar atrophy and white matter disease. These cases expand the clinical heterogeneity of AARS2-related disorders, given that the first and third case represent some of the oldest known survivors of this disease, the second is adult-onset AARS2-related neurological decline without leukodystrophy, and the third is biallelic AARS2-related disorder involving a partial gene deletion.

Opsoclonus consists of bursts of involuntary, multidirectional, back-to-back saccades without an intersaccadic interval. We report a 60-year-old man with post-concussive headaches and disequilibrium who had small amplitude opsoclonus in left gaze, along with larger amplitude flutter during convergence. Examination was otherwise normal and brain MRI was unremarkable. Video-oculography demonstrated opsoclonus predominantly in left gaze and during pursuit in the left hemifield, which improved as post-concussive symptoms improved. Existing theories of opsoclonus mechanisms do not account for this eye position-dependence. We discuss theoretical mechanisms of this behavior, including possible dysfunction of frontal eye field and/or cerebellar vermis neurons; review ocular oscillations in traumatic brain injury; and consider the potential relationship between the larger amplitude flutter upon convergence and post-traumatic ocular oscillations.

The purpose of this consensus paper is to review electrophysiological abnormalities and to provide a guideline of neurophysiological assessments in cerebellar ataxias. All authors agree that standard electrophysiological methods should be systematically applied in all cases of ataxia to reveal accompanying peripheral neuropathy, the involvement of the dorsal columns, pyramidal tracts and the brainstem. Electroencephalography should also be considered, although findings are frequently non-specific. Electrophysiology helps define the neuronal systems affected by the disease in an individual patient and to understand the phenotypes of the different types of ataxia on a more general level. As yet, there is no established electrophysiological measure which is sensitive and specific of cerebellar dysfunction in ataxias. The authors agree that cerebellar brain inhibition (CBI), which is based on a paired-pulse transcranial magnetic stimulation (TMS) paradigm assessing cerebellar-cortical connectivity, is likely a useful measure of cerebellar function. Although its role in the investigation and diagnoses of different types of ataxias is unclear, it will be of interest to study its utility in this type of conditions. The authors agree that detailed clinical examination reveals core features of ataxia (i.e., dysarthria, truncal, gait and limb ataxia, oculomotor dysfunction) and is sufficient for formulating a differential diagnosis. Clinical assessment of oculomotor function, especially saccades and the vestibulo-ocular reflex (VOR) which are most easily examined both at the bedside and with quantitative testing techniques, is of particular help for differential diagnosis in many cases. Pure clinical measures, however, are not sensitive enough to reveal minute fluctuations or early treatment response as most relevant for pre-clinical stages of disease which might be amenable to study in future intervention trials. The authors agree that quantitative measures of ataxia are desirable as biomarkers. Methods are discussed that allow quantification of ataxia in laboratory as well as in clinical and real-life settings, for instance at the patients' home. Future studies are needed to demonstrate their usefulness as biomarkers in pharmaceutical or rehabilitation trials.

This review summarizes topical papers from the fields of neuro-ophthalmology and neuro-otology published from August 2013 to February 2015. The main findings are: (1) diagnostic criteria for pseudotumor cerebri have been updated, and the Idiopathic Intracranial Hypertension Treatment Trial evaluated the efficacy of acetazolamide in patients with mild vision loss, (2) categorization of vestibular disorders through history and ocular motor examination is particularly important in the acute vestibular syndrome, where timely distinction between a central or peripheral localization is essential, (3) the newly described "sagging eye syndrome" provides a mechanical explanation for an isolated esodeviation that increases at distance in the aging population and (4) eye movement recordings better define how cerebellar dysfunction and/or sixth nerve palsy may play a role in other patients with esodeviations that increase at distance.

Cervical dystonia is characterized by abnormal posturing of the head, often combined with tremor-like oscillatory head movements. The nature and source of these oscillatory head movements is controversial, so they were quantified to delineate their characteristics and develop a hypothetical model for their genesis. A magnetic search coil system was used to measure head movements in 14 subjects with cervical dystonia. Two distinct types of oscillatory head movements were detected for most subjects, even when they were not clinically evident. One type had a relatively large amplitude and jerky irregular pattern, and the other had smaller amplitude with a more regular and sinusoidal pattern. The kinematic properties of these two types of oscillatory head movements were distinct, although both were often combined in the same subject. Both had features suggestive of a defect in a central neural integrator. The combination of different types of oscillatory head movements in cervical dystonia helps to clarify some of the current debates regarding whether they should be considered as manifestations of dystonia or tremor and provides novel insights into their potential pathogenesis.

OBJECTIVE Vestibular neuritis is often mimicked by stroke (pseudoneuritis). Vestibular eye movements help discriminate the two conditions. We report vestibulo-ocular reflex (VOR) gain measures in neuritis and stroke presenting acute vestibular syndrome (AVS). METHODS Prospective cross-sectional study of AVS (acute continuous vertigo/dizziness lasting >24 h) at two academic centers. We measured horizontal head impulse test (HIT) VOR gains in 26 AVS patients using a video HIT device (ICS Impulse). All patients were assessed within 1 week of symptom onset. Diagnoses were confirmed by clinical examinations, brain magnetic resonance imaging with diffusion-weighted images, and follow-up. Brainstem and cerebellar strokes were classified by vascular territory-posterior inferior cerebellar artery (PICA) or anterior inferior cerebellar artery (AICA). RESULTS Diagnoses were vestibular neuritis (n = 16) and posterior fossa stroke (PICA, n = 7; AICA, n = 3). Mean HIT VOR gains (ipsilesional [standard error of the mean], contralesional [standard error of the mean]) were as follows: vestibular neuritis (0.52 [0.04], 0.87 [0.04]); PICA stroke (0.94 [0.04], 0.93 [0.04]); AICA stroke (0.84 [0.10], 0.74 [0.10]). VOR gains were asymmetric in neuritis (unilateral vestibulopathy) and symmetric in PICA stroke (bilaterally normal VOR), whereas gains in AICA stroke were heterogeneous (asymmetric, bilaterally low, or normal). In vestibular neuritis, borderline gains ranged from 0.62 to 0.73. Twenty patients (12 neuritis, six PICA strokes, two AICA strokes) had at least five interpretable HIT trials (for both ears), allowing an appropriate classification based on mean VOR gains per ear. Classifying AVS patients with bilateral VOR mean gains of 0.70 or more as suspected strokes yielded a total diagnostic accuracy of 90%, with stroke sensitivity of 88% and specificity of 92%. CONCLUSION Video HIT VOR gains differ between peripheral and central causes of AVS. PICA strokes were readily separated from neuritis using gain measures, but AICA strokes were at risk of being misclassified based on VOR gain alone.

Public Health Concern Dizziness and vertigo are responsible for an estimated 4.4 million emergency department (ED) visits in the United States each year and account for 4% of chief symptoms in the ED.1 Strokes are the underlying cause of ≈3% to 5% of such visits (130 000–220 000).2 These visits are associated with a high cost, estimated now to exceed $10 billion per year in the United States.3 This results from neuroimaging obtained in roughly half the patients1 and admissions for nearly 20%.4 ED physicians worldwide rank vertigo a top priority for developing better diagnostic tools.5 An evidence-based, cost-effective approach to diagnosing acute dizziness and vertigo is needed. ### Diagnostic Errors Improving diagnosis is recognized by the National Academy of Medicine as a public health priority.6 Nearly 10% of strokes are misdiagnosed at first medical contact.7 Of the ≈130 000 to 220 000 patients with stroke presenting with vertigo or dizziness to the ED, it is estimated that perhaps 45 000 to 75 000 are initially missed,3 with misdiagnosis disproportionately affecting the young (age

The study of eye movements not only addresses debilitating neuro-ophthalmological problems but has become an essential tool of basic neuroscience research. Eye movements are a classic way to evaluate brain function-traditionally in disorders affecting the brainstem and cerebellum. Abnormalities of eye movements have localizing value and help narrow the differential diagnosis of complex neurological problems. More recently, using sophisticated behavioral paradigms, measurement of eye movements has also been applied to disorders of the thalamus, basal ganglia, and cerebral cortex. Moreover, in contemporary neuroscience, eye movements play a key role in understanding cognition, behavior, and disorders of the mind. Examples include applications to higher-level decision-making processes as in neuroeconomics and psychiatric and cognitive disorders such as schizophrenia and autism. Eye movements have become valued as objective biomarkers to monitor the natural progression of disease and the effects of therapies. As specific genetic defects are identified for many neurological disorders, ocular motor function often becomes the cornerstone of phenotypic classification and differential diagnosis. Here, we introduce other important applications of eye movement research, including understanding movement disorders affecting the head and limbs. We also emphasize the need to develop standardized test batteries for eye movements of all types including the vestibulo-ocular responses. The evaluation and treatment of patients with cerebellar ataxia are particularly amenable to such an approach.

Here we characterize persistent apogeotropic type of central positional nystagmus, and compare it with the apogeotropic nystagmus of benign paroxysmal positional vertigo involving the lateral canal. Nystagmus was recorded in 27 patients with apogeotropic type of central positional nystagmus (22 with unilateral and five with diffuse cerebellar lesions) and 20 patients with apogeotropic nystagmus of benign paroxysmal positional vertigo. They were tested while sitting, while supine with the head straight back, and in the right and left ear-down positions. The intensity of spontaneous nystagmus was similar while sitting and supine in apogeotropic type of central positional nystagmus, but greater when supine in apogeotropic nystagmus of benign paroxysmal positional vertigo. In central positional nystagmus, when due to a focal pathology, the lesions mostly overlapped in the vestibulocerebellum (nodulus, uvula, and tonsil). We suggest a mechanism for apogeotropic type of central positional nystagmus based on the location of lesions and a model that uses the velocity-storage mechanism. During both tilt and translation, the otolith organs can relay the same gravito-inertial acceleration signal. This inherent ambiguity can be resolved by a ` tilt-estimator circuit' in which information from the semicircular canals about head rotation is combined with otolith information about linear acceleration through the velocity-storage mechanism. An example of how this mechanism works in normal subjects is the sustained horizontal nystagmus that is produced when a normal subject is rotated at a constant speed around an axis that is tilted away from the true vertical (off-vertical axis rotation). We propose that when the tilt-estimator circuit malfunctions, for example, with lesions in the vestibulocerebellum, the estimate of the direction of gravity is erroneously biased away from true vertical. If the bias is toward the nose, when the head is turned to the side while supine, there will be sustained, unwanted, horizontal positional nystagmus (apogeotropic type of central positional nystagmus) because of an inappropriate feedback signal indicating that the head is rotating when it is not.

The phenotypic and genetic spectrum of ataxia with oculomotor apraxia (AOA) disorders is rapidly evolving and new technologies such as genetic mapping using whole exome sequencing reveal subtle distinctions among the various subtypes. We report a novel PNKP mutation in two siblings with progressive ataxia, abnormal saccades, sensorimotor neuropathy and dystonia consistent with the AOA type 4 phenotype. Laboratory evaluation revealed hypoalbuminemia, hypercholesterolemia with elevated LDL, elevated IgE levels and normal α fetoprotein levels. Eye movement examination demonstrated a marked saccade initiation defect with profound hypometric horizontal saccades. Vertical saccades were also affected but less so. Also present were conspicuous thrusting head movements when attempting to change gaze, but rather than an apraxia these were an adaptive strategy to take advantage of an intact vestibulo-ocular reflex to carry the eyes to a new target of interest. This is demonstrated in accompanying videos.

Introduction Pseudoabducens palsy refers to abduction paresis in the absence of a pontine or peripheral nerve process. This finding has been described with mesodiencephalic lesions, and likely has a common mechanism with thalamic esotropia. Case report We describe the case of a 55-year-old man who presented with near-complete ophthalmoparesis, sparing only adduction of the left eye. Magnetic resonance imaging of the brain demonstrated midbrain infarction. Conclusions Pseudoabducens palsy is likely underrecognized, but can be highly localizing when identified. Possible pathophysiologic mechanisms for this finding are discussed.

Describe characteristics of small strokes causing acute vestibular syndrome (AVS).Ambispective cross-sectional study of patients with AVS (acute vertigo or dizziness, nystagmus, nausea/vomiting, head-motion intolerance, unsteady gait) with at least one stroke risk factor from 1999 to 2011 at a single stroke referral center. Patients underwent nonquantitative HINTS "plus" examination (head impulse, nystagmus, test-of-skew plus hearing), neuroimaging to confirm diagnoses (97% by MRI), and repeat MRI in those with initially normal imaging but clinical signs of a central lesion. We identified patients with diffusion-weighted imaging (DWI) strokes ≤10 mm in axial diameter.Of 190 high-risk AVS presentations (105 strokes), we found small strokes in 15 patients (median age 64 years, range 41-85). The most common vestibular structure infarcted was the inferior cerebellar peduncle (73%); the most common stroke location was the lateral medulla (60%). Focal neurologic signs were present in only 27%. The HINTS "plus" battery identified small strokes with greater sensitivity than early MRI-DWI (100% vs 47%, p0.001). False-negative initial MRIs (6-48 hours) were more common with small strokes than large strokes (53% [n = 8/15] vs 7.8% [n = 7/90], p0.001). Nonlacunar stroke mechanisms were responsible in 47%, including 6 vertebral artery occlusions or dissections.Small strokes affecting central vestibular projections can present with isolated AVS. The HINTS "plus" hearing battery identifies these patients with greater accuracy than early MRI-DWI, which is falsely negative in half, up to 48 hours after onset. We found nonlacunar mechanisms in half, suggesting greater risk than might otherwise be assumed for patients with such small infarctions.

ObjectiveTo propose an etiology for a syndrome of bilateral vestibular hypofunction and sound and/or pressure-evoked eye movements with normal hearing thresholds.DesignRetrospective case series.SettingTertiary care referral center.PatientsFour patients with bilateral vestibular hypofunction, sound a

The oculomotor abnormalities with isolated infarction of the cerebellar tonsil are unknown. In a patient with acute infarction of the right tonsil, we found (1) nearly completely abolished ipsilateral smooth pursuit and impaired contralateral pursuit, (2) a low-amplitude ipsilesional right-beating nystagmus without fixation, (3) gaze-holding deficits, and (4) normal vestibulo-ocular reflex. These findings contrast with striking vestibular abnormalities reported with unilateral flocculus and anterior tonsil infarction. Taken together, these findings allow more diagnostic certainty in cerebellar patients, help resolve controversies about interpretation of experimental findings in monkeys, and clarify homologies between the monkey and human cerebellum.

Isolated floccular infarction is extremely rare, and impairments of the vestibulo-ocular reflex (VOR) have not been explored in humans with isolated floccular lesions. The purpose of this study was to examine and report selective impairment of VOR in response to high acceleration using head impulse in a patient with isolated floccular infarction. The patient underwent bedside and laboratory evaluation of vestibular function, which included video-oculography, ocular torsion and the subjective visual vertical, cervical and ocular vestibular-evoked myogenic potentials, bithermal caloric irrigation, rotatory chair test, and the head impulse test (HIT) using search coils. A 70-year-old woman with a unilateral floccular infarction presented with an acute vestibular syndrome with spontaneous nystagmus beating to the lesion side, impaired ipsilesional pursuit, contraversive ocular torsion and tilt of the subjective visual vertical. With rotatory chair testing at low frequencies, horizontal VOR gains were increased. However, VOR gains were decreased with the higher-frequency, higher-speed HIT. While HIT is often normal in patients with central vestibular disorders, decreased HIT responses do not exclude an isolated cerebellar lesion as a cause of the acute vestibular syndrome.

Background and Purpose— Strokes can be distinguished from benign peripheral causes of acute vestibular syndrome using bedside oculomotor tests (head impulse test, nystagmus, test-of-skew). Using head impulse test, nystagmus, test-of-skew is more sensitive and less costly than early magnetic resonance imaging for stroke diagnosis in acute vestibular syndrome but requires expertise not routinely available in emergency departments. We sought to begin standardizing the head impulse test, nystagmus, test-of-skew diagnostic approach for eventual emergency department use through the novel application of a portable video-oculography device measuring vestibular physiology in real time. This approach is conceptually similar to ECG to diagnose acute cardiac ischemia. Methods— Proof-of-concept study (August 2011 to June 2012). We recruited adult emergency department patients with acute vestibular syndrome defined as new, persistent vertigo/dizziness, nystagmus, and (1) nausea/vomiting, (2) head motion intolerance, or (3) new gait unsteadiness. We recorded eye movements, including quantitative horizontal head impulse testing of vestibulo-ocular-reflex function. Two masked vestibular experts rated vestibular findings, which were compared with final radiographic gold-standard diagnoses. Masked neuroimaging raters determined stroke or no stroke using magnetic resonance imaging of the brain with diffusion-weighted imaging obtained 48 hours to 7 days after symptom onset. Results— We enrolled 12 consecutive patients who underwent confirmatory magnetic resonance imaging. Mean age was 61 years (range 30–73), and 10 were men. Expert-rated video-oculography–based head impulse test, nystagmus, test-of-skew examination was 100% accurate (6 strokes, 6 peripheral vestibular). Conclusions— Device-based physiological diagnosis of vertebrobasilar stroke in acute vestibular syndrome should soon be possible. If confirmed in a larger sample, this bedside eye ECG approach could eventually help fulfill a critical need for timely, accurate, efficient diagnosis in emergency department patients with vertigo or dizziness who are at high risk for stroke.

Objectives Dizziness and vertigo account for about 4 million emergency department (ED) visits annually in the United States, and some 160,000 to 240,000 (4% to 6%) have cerebrovascular causes. Stroke diagnosis in ED patients with vertigo/dizziness is challenging because the majority have no obvious focal neurologic signs at initial presentation. The authors sought to compare the accuracy of two previously published approaches purported to be useful in bedside screening for possible stroke in dizziness: a clinical decision rule (head impulse, nystagmus type, test of skew [HINTS]) and a risk stratification rule (age, blood pressure, clinical features, duration of symptoms, diabetes [ABCD2]). Methods This was a cross-sectional study of high-risk patients (more than one stroke risk factor) with acute vestibular syndrome (AVS; acute, persistent vertigo or dizziness with nystagmus, plus nausea or vomiting, head motion intolerance, and new gait unsteadiness) at a single academic center. All underwent neurootologic examination, neuroimaging (97.4% by magnetic resonance imaging [MRI]), and follow-up. ABCD2 risk scores (0–7 points), using the recommended cutoff of ≥4 for stroke, were compared to a three-component eye movement battery (HINTS). Sensitivity, specificity, and positive and negative likelihood ratios (LR+, LR–) were assessed for stroke and other central causes, and the results were stratified by age. False-negative initial neuroimaging was also assessed. Results A total of 190 adult AVS patients were assessed (1999–2012). Median age was 60.5 years (range = 18 to 92 years; interquartile range [IQR] = 52.0 to 70.0 years); 60.5% were men. Final diagnoses were vestibular neuritis (34.7%), posterior fossa stroke (59.5% [105 infarctions, eight hemorrhages]), and other central causes (5.8%). Median ABCD2 was 4.0 (range = 2 to 7; IQR = 3.0 to 4.0). ABCD2 ≥ 4 for stroke had sensitivity of 61.1%, specificity of 62.3%, LR+ of 1.62, and LR– of 0.62; sensitivity was lower for those younger than 60 years old (28.9%). HINTS stroke sensitivity was 96.5%, specificity was 84.4%, LR+ was 6.19, and LR– was 0.04 and did not vary by age. For any central lesion, sensitivity was 96.8%, specificity was 98.5%, LR+ was 63.9, and LR– was 0.03 for HINTS, and sensitivity was 99.2%, specificity was 97.0%, LR+ was 32.7, and LR– was 0.01 for HINTS “plus” (any new hearing loss added to HINTS). Initial MRIs were falsely negative in 15 of 105 (14.3%) infarctions; all but one was obtained before 48 hours after onset, and all were confirmed by delayed MRI. Conclusions HINTS substantially outperforms ABCD2 for stroke diagnosis in ED patients with AVS. It also outperforms MRI obtained within the first 2 days after symptom onset. While HINTS testing has traditionally been performed by specialists, methods for empowering emergency physicians (EPs) to leverage this approach for stroke screening in dizziness should be investigated.

OBJECTIVE The video head impulse test (HIT) measures vestibular function (vestibulo-ocular reflex [VOR] gain - ratio of eye to head movement), and, in principle, could be used to make a distinction between central and peripheral causes of vertigo. However, VOG recordings contain artifacts, so using unfiltered device data might bias the final diagnosis, limiting application in frontline healthcare settings such as the emergency department (ED). We sought to assess whether unfiltered data (containing artifacts) from a video-oculography (VOG) device have an impact on VOR gain measures in acute vestibular syndrome (AVS). METHODS This cross-sectional study compared VOG HIT results 'unfiltered' (standard device output) versus 'filtered' (artifacts manually removed) and relative to a gold standard final diagnosis (neuroimaging plus clinical follow-up) in 23 ED patients with acute dizziness, nystagmus, gait disturbance and head motion intolerance. RESULTS Mean VOR gain assessment alone (unfiltered device data) discriminated posterior inferior cerebellar artery (PICA) strokes from vestibular neuritis with 91% accuracy in AVS. Optimal stroke discrimination cut points were bilateral VOR gain >0.7099 (unfiltered data) versus >0.7041 (filtered data). For PICA stroke sensitivity and specificity, there was no clinically-relevant difference between unfiltered and filtered data-sensitivity for PICA stroke was 100% for both data sets and specificity was almost identical (87.5% unfiltered versus 91.7% filtered). More impulses increased gain precision. CONCLUSIONS The bedside HIT remains the single best method for discriminating between vestibular neuritis and PICA stroke in patients presenting AVS. Quantitative VOG HIT testing in the ED is associated with frequent artifacts that reduce precision but not accuracy. At least 10-20 properly-performed HIT trials per tested ear are recommended for a precise VOR gain estimate.

An attractive hypothesis about how the brain learns to keep its motor commands accurate is centered on the idea that the cerebellar cortex associates error signals carried by climbing fibers with simultaneous activity in parallel fibers. Motor learning can be impaired if the error signals are not transmitted, are incorrect, or are misinterpreted by the cerebellar cortex. Learning might also be impaired if the brain is overwhelmed with a sustained barrage of meaningless information unrelated to simultaneously appearing error signals about incorrect performance. We test this concept in subjects with syndrome of oculopalatal tremor (OPT), a rare disease with spontaneous, irregular, roughly pendular oscillations of the eyes thought to reflect an abnormal, synchronous, spontaneous discharge to the cerebellum from the degenerating neurons in the inferior olive. We examined motor learning during a short-term, saccade adaptation paradigm in patients with OPT and found a unique pattern of disturbed adaptation, quite different from the abnormal adaption when the cerebellum is involved directly. Both fast (seconds) and slow (minutes) timescales of learning were impaired. We suggest that the spontaneous, continuous, synchronous output from the inferior olive prevents the cerebellum from receiving the error signals it needs for appropriate motor learning. The important message from this study is that impaired motor adaptation and resultant dysmetria is not the exclusive feature of cerebellar disorders, but it also highlights disorders of the inferior olive and its connections to the cerebellum.

Vertical supranuclear gaze palsy (VSGP) is a key clinical feature in patients with Niemann-Pick type C disease (NP-C), a rare, autosomal recessive, neuro-visceral disorder caused by mutations in either the NPC1 or NPC2 gene. VSGP is present in approximately 65 % of the cases and is, with gelastic cataplexy, an important risk indicator for NP-C. VSGP in NP-C is characterized by a paralysis of vertical saccades, especially downward, with the slow vertical eye movement systems (smooth pursuit and the vestibulo-ocular reflex) spared in the early phase of the disease. This dissociation is caused by a selective vulnerability of the neurons in the rostral interstitial nuclei of the medial longitudinal fasciculus (riMLF) in NP-C. Here we discuss VSGP in NP-C and how clinicians can best elicit this sign.

In this study, we used manual delineation of high-resolution magnetic resonance imaging (MRI) to determine the spatial and temporal characteristics of the cerebellar atrophy in spinocerebellar ataxia type 2 (SCA2). Ten subjects with SCA2 were compared to ten controls. The volume of the pons, the total cerebellum, and the individual cerebellar lobules were calculated via manual delineation of structural MRI. SCA2 showed substantial global atrophy of the cerebellum. Furthermore, the degeneration was lobule specific, selectively affecting the anterior lobe, VI, Crus I, Crus II, VIII, uvula, corpus medullare, and pons, while sparing VIIB, tonsil/paraflocculus, flocculus, declive, tuber/folium, pyramis, and nodulus. The temporal characteristics differed in each cerebellar subregion: (1) duration of disease: Crus I, VIIB, VIII, uvula, corpus medullare, pons, and the total cerebellar volume correlated with the duration of disease; (2) age: VI, Crus II, and flocculus correlated with age in control subjects; and (3) clinical scores: VI, Crus I, VIIB, VIII, corpus medullare, pons, and the total cerebellar volume correlated with clinical scores in SCA2. No correlations were found with the age of onset. Our extrapolated volumes at the onset of symptoms suggest that neurodegeneration may be present even during the presymptomatic stages of disease. The spatial and temporal characteristics of the cerebellar degeneration in SCA2 are region specific. Furthermore, our findings suggest the presence of presymptomatic atrophy and a possible developmental component to the mechanisms of pathogenesis underlying SCA2. Our findings further suggest that volumetric analysis may aid in the development of a non-invasive, quantitative biomarker.

Background/aims Visually guided saccades and gaze-fixation ability were recorded in patients with early Parkinson9s disease (PD). Methods Magnetic search coil system was used to measure horizontal and vertical eye positions. Results ‘Staircase’ visually guided saccades (multiple hypometric saccades separated by an intersaccadic interval) and ‘staircase’ square-wave jerks (SWJ) were present in all patients. The SWJ amplitude (total amplitude of the series of hypometric saccades comprising the SWJ) was abnormally large (mean 2°). SWJ frequency was also abnormally high (50–70 intrusions/min). Conclusion Loss of dopaminergic neurons in the substantia nigra pars compacta leading to phasic excitation of the substantia nigra pars reticulata and, in turn, phasic inhibition of the superior colliculus (SC), may account for ‘staircase’ visually guided saccades in these patients. This mechanism, however, does not explain abnormally large SWJ, which in the traditional view results from decreased inhibition upon SC. The abnormally large SWJ could be due to a compensatory increase in frontal eye field activity secondary to the increased inhibition upon the SC. Abnormally large and frequent SWJ are often used clinically to distinguish multi-system atrophy from idiopathic PD. Our study, however, suggests that idiopathic PD cannot be excluded if the patient has large-amplitude SWJ.

To examine patterns of executive and oculomotor control in a group of both boys and girls with attention-deficit/hyperactivity disorder (ADHD).Cross-sectional study of 120 children aged 8 to 12 years, including 60 with ADHD (24 girls) and 60 typically developing controls (29 girls). Oculomotor paradigms included visually guided saccades (VGS), antisaccades, memory-guided saccades, and a go/no-go test, with variables of interest emphasizing response preparation, response inhibition, and working memory.As a group, children with ADHD demonstrated significant deficits in oculomotor response preparation (VGS latency and variability) and response inhibition but not working memory. Girls, but not boys with ADHD, had significantly longer VGS latencies, even after controlling for differences in ADHD symptom severity. The ADHD subtypes did not differ on response preparation or inhibition measures; however, children with the Inattentive subtype were less accurate on the working memory task than those with the Combined subtype.Sex differences in children with ADHD extend beyond symptom presentation to the development of oculomotor control. Saccade latency may represent a specific deficit among girls with ADHD.

Background: Most patients with acute vestibular syndrome have vestibular neuritis or labyrinthitis. Some harbour strokes that can only be differentiated on the basis of subtle eye movement findings, including nystagmus. Peripheral nystagmus should be enhanced by removal of visual fixation. Current bedside methods for removing fixation require expensive equipment or technical skill not routinely available. We sought to test a new method for blocking fixation. Methods: Proof-of-concept study for a new bedside oculomotor diagnostic test using an established physiological measurement of eye movements (electro-oculography (EOG)) as the reference standard. We sampled unselected patients undergoing caloric testing (surrogate model for neuritis) in an academic vestibular clinic. During the brief (30–60 s) decay phase of caloric-induced peripheral vestibular nystagmus, we shone a penlight in the left eye while intermittently occluding the right. We assessed nystagmus intensity (slow-phase velocity) clinically in all subjects and quantified change in two exemplar cases. Results: Caloric responses frequently decayed before the test was complete, and artefacts rendered many EOGs uninterpretable during the short decay period. A clinically evident increase in nystagmus was seen 18 times in 10 patients and corroborated by EOG in 15. In quantified cases, slow-phase velocity increased as expected (mean change +42%) with fixation blocked. Conclusion: The penlight-cover test could offer a low-cost, simple means of disrupting visual fixation in clinical settings where differentiating peripheral from central vestibular disorders is crucial, such as the emergency department. Prospective studies are needed to determine the test’s utility for excluding dangerous central causes among patients with suspected peripheral lesions.

To assess how frequently cardiovascular dizziness is vertigo. Recent studies suggest providers do not consider cardiovascular causes when a patient reports true vertigo (spinning/motion) as opposed to presyncope (impending faint). It is known that cardiovascular disease causes dizziness, but unknown how often such dizziness is vertiginous, as opposed to presyncopal.Systematic review of observational studies was made: Search--electronic (MEDLINE, EMBASE) and manual (references of eligible articles) search for English-language studies (1972-2007).Inclusions Studies ofor=5 patients with confirmed cardiovascular causes for dizziness and reporting a proportion with vertigo were included. Two independent reviewers selected studies for inclusion, with differences adjudicated by a third. Study characteristics and dizziness-type proportions were abstracted. Studies were rated on methodology and quality of dizziness definitions. Differences were resolved by consensus.We identified 1,506 citations, examined 125 full manuscripts, and included 5 studies. Principal reasons for exclusion were: abstracts--lack of original data, no cardiovascular diagnosis, or confounding exposure/disease (74%); manuscripts--failure to distinguish vertigo from other dizziness types (78%). In the three studies not using vertigo as an entry criterion (representing 1,659 patients with myocardial infarction, orthostatic hypotension, or syncope), vertigo was present in 63% (95% CI 57-69%) of cardiovascular patients with dizziness and the only dizziness type in 37% (95% CI 31-43%). Limitations include modest study quality and non-uniform definitions for vertigo.Published data suggest that dizziness from primary cardiovascular disease may often be vertigo. Future research should assess prospectively whether dizziness type is a meaningful predictor for or against a cardiovascular diagnosis.

Tremor disorders pose fundamental questions about disease mechanisms, and challenges to successful neurotherapeutics: What causes motor circuits to oscillate in disorders in which the central nervous system otherwise seems normal? How does inheritance 'determine' the clinical phenotype in familial tremor disorders? Here, we address these questions. Analogies between the neural circuits controlling rapid eye movements (saccades) and those controlling limb movements allow us to translate the interpretations from the saccadic systems to the limb movement system. Moreover, the relatively well understood neurophysiology of the ocular motor system offers a unique opportunity to test specific hypotheses about normal and abnormal motor control of both eye and limb movements. We describe a new familial disorder--'micro-saccadic oscillations and limb tremor (microSOLT)'--in a mother and daughter who had tiny saccadic oscillations of the eyes and tremor of the hands. This unique oscillatory movement disorder resembles other common tremor disorders (such as essential tremor) that occur in patients who have an otherwise normally functioning central nervous system. We hypothesize that microSOLT is caused by an inherited abnormality that results in abnormal membrane properties causing reduced external inhibition in the premotor neurons that generate the high-frequency discharge (burst) for saccades and for ballistic limb movements. To test this hypothesis, we recorded hand tremor and eye movements in two patients with microSOLT and particularly during natural circumstances when inhibition of the premotor saccadic burst neurons is removed (e.g. eye closure). We then simulated a conductance-based model for the premotor commands which included excitatory and reciprocally inhibitory burst neurons. The structure of this physiologically realistic model was based upon known cell types and anatomical connections in the brainstem (for saccades) and the thalamus (for limb movements). The physiological phenomenon of post-inhibitory rebound in premotor burst neurons makes the circuit inherently unstable and prone to oscillate unless prevented by external inhibition. Indeed, with simulated reduction of external inhibition (in this case glycinergic), saccadic oscillations and limb tremor were reproduced. Our results suggest that a single-inherited deficit can alter membrane properties, which impairs inhibition in an inherently unstable neural circuit causing the eye and limb oscillations in microSOLT. This concept has broad implications for understanding the mechanism and designing rationale pharmacotherapy for abnormal oscillations and may be applicable to other common disorders in which there are no structural abnormalities in the brain such as essential tremor.

Fragile X and Turner syndromes are two X-chromosome-related disorders associated with executive function and visual spatial deficits. In the present study, we used ocular motor paradigms to examine evidence that disruption to different neurological pathways underlies these deficits. We tested 17 females with fragile X, 19 females with Turner syndrome, and 40 females with neither disorder who comprised the comparison group. Group differences emerged for both the fragile X and Turner syndrome groups, each relative to the comparison group: Females with fragile X had deficits in generating memory-guided saccades, predictive saccades, and saccades made in the overlap condition of a gap/overlap task. Females with Turner syndrome showed deficits in generating memory-guided saccades, but not during either the predictive saccade or gap/overlap task. Females with Turner syndrome, but not females with fragile X, showed deficits in visually guided saccades and anti-saccades. These findings indicate that different brain regions are affected in the two disorders, and suggest that different pathways lead to the similar cognitive phenotypes described for fragile X and Turner syndromes.

The signals for adduction during conjugate horizontal eye movements are carried through the medial longitudinal fasciculus (MLF). Lesions in this pathway cause internuclear ophthalmoplegia (INO), characterized by impaired ipsilesional adduction, often with nystagmus of the contralateral abducting eye. Usually with INO straight-ahead fixation appears steady. Here we demonstrate quantitative recordings and videos of 2 unusual patterns of saccadic intrusions in a patient with bilateral INO and discuss a plausible mechanism.

A challenge for the clinical neurologist is to decide which of the myriad patients with symptoms of dizziness, lightheadedness, or imbalance have a genuine vestibular disorder, be it peripheral or central. The clinical examination is often the key. A series of systematically applied, physiologically based maneuvers, designed to probe static and dynamic function of the vestibulo-ocular reflexes and the individual labyrinthine sensors, will almost always reveal the evidence of a vestibular system anomaly, which either clarifies the diagnosis or points to a need for a further evaluation. This chapter will describe these maneuvers and indicate their diagnostic usefulness. They include dynamic visual acuity, occlusive ophthalmoscopy, head impulse (rotational vestibulo-ocular reflex) and head heave (translational vestibulo-ocular reflex) testing, mastoid vibration-induced nystagmus (equivalent of a hot-water caloric stimulus in a patient with unilateral vestibular loss), hyperventilation-induced nystagmus (abnormal in fistula, craniocervical junction anomalies, compressive and demyelinating lesions, and cerebellar degenerations), Valsalva-induced nystagmus (abnormal in fistula and craniocervical junction anomalies), head-shaking–induced nystagmus (vertical nystagmus after horizontal head shaking points to a central disorder), positional nystagmus (lateral canal, posterior canal, central) and soundinduced nystagmus (superior canal dehiscence). When combined with a careful examination of eye alignment, gaze holding, saccade accuracy and speed, and smooth pursuit, a central or peripheral localization is usually possible. BASIC PHYSIOLOGICAL PRINCIPLES AND ANATOMICAL ORGANIZATION The clinical evaluation of the patient whose symptoms suggest vestibular dysfunction relies upon a solid understanding of vestibular physiology and anatomy and of the psychophysiological aspects of normal and abnormal vestibular sensation. The term vestibular will be used here in its broadest sense as the mechanism for detecting the attitude of the head with respect to gravity and to any movement of the head within the environment and also for generating the appropriate compensatory motor responses that assure clear vision and steady balance in response to movements of the head and body.

Rebound nystagmus is a transient nystagmus that occurs on resuming the straight-ahead position after prolonged eccentric gaze. Even though rebound nystagmus is commonly associated with gaze-evoked nystagmus (GEN), development of rebound nystagmus in a different plane of gaze has not been described. We report a patient with episodic ataxia type 2 who showed transient upbeat nystagmus on resuming the straight-ahead position after sustained lateral gaze that had induced GEN and downbeat nystagmus. The rebound upbeat nystagmus may be ascribed to a shifting null in the vertical plane as a result of an adaptation to the downbeat nystagmus that developed during lateral gaze.

Two hereditary ataxia syndromes show distinct profiles of region-specific atrophy and ocular motor deficits. Selective pontine atrophy is associated with slowed saccades in ataxin-2 mutations, and selective floccular atrophy is associated with impaired pursuit and gaze-holding abnormalities in Ca(V)2.1 mutations. Although the flocculus seems to be spared relative to the pons in ataxin-2 mutations, and pursuit and gaze-holding appear to be relatively normal, these can be difficult to assess at the bedside, as corrective saccades are also slow and hard to discern. Here, we show the presence of significant floccular atrophy compared with controls in both ataxin-2 and Ca(V)2.1 mutations, which raises the possibility that abnormalities of smooth pursuit or gaze-holding are present in both conditions.

We document a new oculomotor phenomenon in a patient with pathologically proven progressive supranuclear gaze palsy (PSP), namely that vertical gaze excursion improves with larger pursuit targets. We used computerised video-oculography during vertical smooth pursuit eye movements (SPEM) of circular targets of diameter 0.16 degrees and 16 degrees, sinusoidally oscillating at 0.08 Hz (peak-to-peak amplitude 49 degrees). Increasing target size improved vertical gaze excursion from 10 degrees to 25 degrees. There was no concomitant increase in slow phase eye velocity. The findings could be explained by a potentiation of the position control mechanism of pursuit by target size due to increased activation of brainstem pursuit-optokinetic pathways and to higher order attentional mechanisms. This observation may be useful in the clinical assessment of PSP patients with severe neck rigidity in whom the doll's head-eye manoeuvre cannot be performed by comparing the degree of vertical gaze palsy during smooth pursuit testing between at least two differently sized targets and observing whether there is a larger excursion in response to a large target such as a newspaper.

In spinocerebellar ataxia type 6 (SCA6), the vestibular dysfunction and its correlation with other clinical parameters require further exploration. We determined vestibular responses over a broad range of stimulus acceleration in 11 patients with SCA6 (six men, age range=33–72 years, mean age±SD=59±12 years) using bithermal caloric irrigations, rotary chair, and head impulse tests. Correlations were also pursued among disability scores, as measured using the International Cooperative Ataxia Rating Scale, disease duration, age at onset, cytosine-adenine-guanine (CAG) repeat length, and the gain of the vestibulo-ocular reflex (VOR). In response to relatively low-acceleration, low-frequency rotational and bithermal caloric stimuli, the VOR gains were normal or increased regardless of the severity of disease. On the other hand, with relatively high-acceleration, high-frequency head impulses, there was a relative increase in gain in the mildly affected patients and a decrease in gain in the more severely affected patients and gains were negatively correlated with the severity of disease (Spearman correlation, R=−0.927, p

Background: We used ocular motor paradigms to examine whether or not saccades are impaired in individuals with high functioning autism (HFA). Methods: We recorded eye movements in patients with HFA (n=11), and in normal adolescents (n=11) on anti-saccade, memory-guided saccade (MGS), predictive saccade and gap/overlap tasks. Results: Compared with the normal subjects, patients with HFA had (1) a significantly higher percentage of directional errors on the anti-saccade task (63.2% versus 26.6%), (2) a significantly higher percentage of response suppression errors on a MGS task (60.3% versus 29.5%) and (3) a significantly lower percentage of predictive eye movements on a predictive saccade task. They also showed longer latencies on a MGS task and for all conditions tested on a gap/null/overlap task (fixation target extinguished before, simultaneously, or after the new peripheral target appeared). When the latencies during the gap condition were subtracted from the latencies in the overlap condition, there was no difference between patients and normals. Conclusions: Abnormalities in ocular motor function in patients with HFA provide preliminary evidence for involvement of a number of brain regions in HFA including the dorsolateral prefrontal cortex (dlPFC) and the frontal eye fields (FEFs) and possibly the basal ganglia and parietal lobes.

Rapid head movements associated with a change in fixation (head saccades) have been reported to be slow in cervical dystonia (CD). Such slowing is typically measured as an increase in time to complete a movement. The mechanisms responsible for this slowing are poorly understood.We measured head saccades in 11 CD patients and 11 healthy subjects using a magnetic search coil technique.Head saccades in CD took longer to reach a desired target location. This longer duration was due to multiple pauses in the trajectory of the head movement. The head velocity of each segment of the (interrupted) head movement was appropriate for the desired total movement amplitude. The head velocity was, however, higher for the amplitude of the individual interrupted movements. These results suggest that brain programs the proper head movement amplitude, but the movement is interrupted by pathological pauses.Voluntary head saccades have a longer duration in CD due to frequent pauses. The frequent pauses reflect pathological interruptions of normally programmed intended head movement.