Vertical Gaze Research Articles

Eye movement disorders in inborn errors of metabolism: A quantitative analysis of 37 patients.

Inborn errors of metabolism are genetic disorders that need to be recognized as early as possible because treatment may be available. In late‐onset forms, core symptoms are movement disorders, psychiatric symptoms, and cognitive impairment. Eye movement disorders are considered to be frequent too, although specific knowledge is lacking. We describe and analyze eye movements in patients with an inborn error of metabolism, and see whether they can serve as an additional clue in the diagnosis of particularly late‐onset inborn errors of metabolism. Demographics, disease characteristics, and treatment data were collected. All patients underwent a standardized videotaped neurological examination and a video‐oculography. Videos are included. We included 37 patients with 15 different inborn errors of metabolism, including 18 patients with a late‐onset form. With the exception of vertical supranuclear gaze palsy in Niemann‐Pick type C and external ophthalmolplegia in Kearns‐Sayre syndrome, no relation was found between the type of eye movement disorder and the underlying metabolic disorder. Movement disorders were present in 29 patients (78%), psychiatric symptoms in 14 (38%), and cognitive deficits in 26 patients (70%). In 87% of the patients with late‐onset disease, eye movement disorders were combined with one or more of these core symptoms. To conclude, eye movement disorders are present in different types of inborn errors of metabolism, but are often not specific to the underlying disorder. However, the combination of eye movement disorders with movement disorders, psychiatric symptoms, or cognitive deficits can serve as a diagnostic clue for an underlying late‐onset inborn error of metabolism.

Capacitive eye tracker made of fractured carbon nanotube-paper composites for wearable applications

The uniqueness of eyes, facial geometry, and gaze direction makes eye tracking a very challenging technological pursuit. Although camera-based eye-tracking systems are popular, the obtrusiveness of their bulky equipment along with their high computational cost and power consumption is considered problematic for wearable applications. Noncontact gaze monitoring using capacitive sensing technique has been attempted but failed due to low sensitivity and parasitic capacitance. Here, we study the interaction between a novel capacitive sensor and eye movement for wearable eye-tracking. The capacitive sensors are made of a pair of asymmetric electrodes; one comprising carbon nanotube-paper composite fibers (CPC) and the other being a rectangular metal electrode. The interaction between the asymmetric sensor and a spherical object mimicking an eyeball is analyzed numerically. Using a face simulator, both single- and differential capacitive measurements are characterized with respect to proximity, geometry, and human body charge. Using a prototype eye tracker, multiple sensor locations are studied to determine the optimal configurations. The capacitive responses to vertical and horizontal gaze directions are analyzed in comparison to those of a commercial eye tracking system. The performance is demonstrated for sensitive eye-movement tracking, closed-eye monitoring, and human-machine interface. This research has important implications for the development of capacitive, wearable eye trackers, which can facilitate fields of human-machine interface, cognitive monitoring, neuroscience research, and rehabilitation.

Quadrigeminal Miracle: Regaining Hearing

Pineal region tumors are classically presented with vertical gaze palsy, hypothalamic symptoms, or, more often, hydrocephalus, by obstructing the aqueduct. This case report describes a patient with obstructive hydrocephalus and a hearing loss as an initial complaint of pineal region tumor.

Atypical Parkinson's syndrome in old age

Atypical Parkinson syndromes represent aneuropathologically heterogeneous group and include the clinical entities dementia with Lewy bodies (DLB), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). The DLB and MSA are characterized by deposition of the protein alpha-synuclein (synucleinopathy), PSP and CBD are characterized by deposition of tau protein, often in the form of neurofibrillary tangles in nerve and glial cells (tauopathy). Misfolding and aggregation of the aforementioned proteins causes degeneration of the affected cell populations but the disease also spreads to anatomically neighboring brain regions, thus contributing to disease progression. The clinical characteristics (poor response to dopaminergic treatment, ataxia, apraxia, vertical gaze palsy and rapid progression) enable a differentiation from idiopathic Parkinson's disease.

Acute percheron infarction: a precision learning

BackgroundSo far, the diagnosis of acute artery of percheron (AOP) infarction is uncommon. In this study, patients with acute AOP infarction were studied to explore the relationship of imaging findings, clinical manifestations and prognosis of acute AOP infarction.MaterialsA total of 23 patients with acute AOP infarction in our institution from 2014 to 2019 were reviewed retrospectively. All cases were evaluated by computed tomography (CT) and magnetic resonance imaging (MRI). The modified Rankin scale (MRS), blood examination, electrocardiogram and transthoracic echocardiography were used for detailed clinical and prognostic evaluation. All standard risk factors for these patients were recorded. The MRS scores were performed 90 days after discharge.ResultsFour different types of acute AOP infarction were identified: (a) bilateral paramedian thalamic infarction (BPTI, 52%); (b) bilateral paramedian thalamic with rostral midbrain infarction (BPTRMI, 30%), (c) bilateral paramedian and anterior thalamic infarction (BPATI, 13%), and (d) bilateral paramedian thalamic with red nuclei infarction (BPTRNI, 4%). These patients had consciousness disorder, memory dysfunctions, vertical gaze paresis and mesencephalothalamic syndrome. The 65% of patients with BPTI and BPATI experienced relatively good functional recovery and could carry out daily life activities (MRS score ≤ 2). However, patients with BPTRMI may have an unfavorable outcome.ConclusionsAlthough the clinical features are variable, DWI or ADC map can improve the diagnosis of acute AOP infarction patterns. Acute AOP occlusion requires immediate diagnosis and treatment to obtain more favorable outcome and avoid additional unnecessary procedures.

Vertical One-and-a-Half Syndrome with Pseudoabducens Palsy and Midbrain Horizontal Gaze Paresis

ABSTRACT The rostral mesencephalon may influence ocular motility in the vertical, horizontal, and torsional trajectories through intricate supranuclear, internuclear, and infranuclear neural networks. Strategic unilateral midbrain lesions may result in contralateral horizontal gaze palsy with saccadic failure due to combined interruption of supranuclear corticofugal fibers from the frontal eye field and colliculofugal fibers from the superior colliculus. In this article, we report a patient who sustained combined vertical and horizontal gaze deficits after a single infarct involving the mesodiencephalic junction. The neural substrate for each deficit is briefly discussed in light of clinical findings. This case presented a triad of three distinct syndromes of horizontal gaze paresis, vertical one-and-a-half syndrome, and pseudoabducens palsy due to damage of nuclear and supranuclear projections within the rostral mesencephalon. This combination was due to a single embolic infarct in the territory of the posterior thalamosubthalamic artery (artery of Percheron) that arises at the basilar bifurcation. Coexistence of these phenomena exemplified how rostral midbrain lesions may affect ocular motility in the vertical, horizontal, and torsional planes, along with disruption of normal vergence control.

201 Management of an unusual presentation of spontaneous intracranial hypotension (SIH)

A 49-year-old woman presented with 9 months of progressive cognitive decline and somnolence. In the last few weeks she developed right hand tremor, unsteadiness and urinary incontinence, which improved after lying flat. There was no headache. Examination findings included vertical gaze restriction, hypomimia, right-sided rest tremor, rigidity and bradykinesia, globally brisk reflexes and an unsteady gait. She scored 50/100 on the Addenbrooke’s Cognitive Examination.Brain MRI showed features consistent with intracranial hypotension with marked ‘brain sag’ but standard imaging did not identify the site of the leak. Two blind blood patches were followed by only transient symptomatic improvement. Initial Digital Subtraction Myelogram (DSM) was non-diagnostic, but repeat DSM identified a leak at C6–7 with an irregular diverticulum/CSF-venous fistula.A CT-guided fibrin patch injected at C6/7 resulted in transient improvement. Finally, a neurosurgical procedure was performed to coagulate the venous plexus adjacent to the C7 nerve root. This effected a dramatic and sustained improvement in her cognitive and motor symptoms.SIH is a treatable cause of cognitive decline and parkinsonism. DSM is a novel approach to localising CSF leaks. This is the first reported cognitive presentation of SIH where identification of a CSF leak with DSM led to successful surgical treatment.saamir.mohideen@nhs.net

Video-oculographic biomarkers for evaluating vertical ocular dysfunction in progressive supranuclear palsy

IntroductionProgressive supranuclear palsy (PSP) patients show reduced amplitude and velocity of vertical saccades, but saccadic abnormalities have also been reported in Parkinson's disease (PD). We investigated amplitude and velocity of vertical saccades in PSP and PD patients, to establish the best video-oculographic (VOG) parameters for PSP diagnosis. MethodsFifty-one PSP patients, 113 PD patients and 40 controls were enrolled. The diagnosis was performed on a clinico-radiological basis (MR Parkinsonism index [MRPI] and MRPI 2.0). We used VOG to assess the diagnostic performances of saccadic amplitude, peak velocity, and their product (AxV) in upward or downward direction and in vertical gaze (upward and downward averaged) in distinguishing PSP from PD patients. The vestibulo-ocular reflex, necessary to establish the supranuclear nature of ocular dysfunction, was evaluated clinically. ResultsPSP patients showed significantly reduced amplitude and peak velocity of ocular saccades in upward and downward directions compared to PD and healthy subjects. In PD patients, upward gaze amplitude was lower than in controls. In vertical gaze, the peak velocity showed 99.1% specificity and 54.7% sensitivity for PSP classification. The AxV product showed high specificity (94.7%) and sensitivity (84.3%) and yielded higher accuracy (91.5%) than velocity and amplitude used alone in distinguishing PSP from PD. ConclusionOur study demonstrates that the peak velocity of vertical saccades was a very low sensitive parameter and cannot be used alone for PSP diagnosis. A new index combining amplitude and peak velocity in vertical gaze seems the most suitable video-oculographic biomarker for differentiating PSP from PD and controls.

Eye tracking identifies biomarkers in α-synucleinopathies versus progressive supranuclear palsy

ObjectivesThis study (1) describes and compares saccade and pupil abnormalities in patients with manifest alpha-synucleinopathies (αSYN: Parkinson’s disease (PD), Multiple System Atrophy (MSA)) and a tauopathy (progressive supranuclear palsy (PSP)); (2) determines whether patients with rapid-eye-movement sleep behaviour disorder (RBD), a prodromal stage of αSYN, already have abnormal responses that may indicate a risk for developing PD or MSA.MethodsNinety (46 RBD, 27 PD, 17 MSA) patients with an αSYN, 10 PSP patients, and 132 healthy age-matched controls (CTRL) were examined with a 10-min video-based eye-tracking task (Free Viewing). Participants were free to look anywhere on the screen while saccade and pupil behaviours were measured.ResultsPD, MSA, and PSP spent more time fixating the centre of the screen than CTRL. All patient groups made fewer macro-saccades (> 2◦ amplitude) with smaller amplitude than CTRL. Saccade frequency was greater in RBD than in other patients. Following clip change, saccades were temporarily suppressed, then rebounded at a slower pace than CTRL in all patient groups. RBD had distinct, although discrete saccade abnormalities that were more marked in PD, MSA, and even more in PSP. The vertical saccade rate was reduced in all patients and decreased most in PSP. Clip changes produced large increases or decreases in screen luminance requiring pupil constriction or dilation, respectively. PSP elicited smaller pupil constriction/dilation responses than CTRL, while MSA elicited the opposite.ConclusionRBD patients already have discrete but less pronounced saccade abnormalities than PD and MSA patients. Vertical gaze palsy and altered pupil control differentiate PSP from αSYN.

A data-driven model of brain volume changes in progressive supranuclear palsy.

The most common clinical phenotype of progressive supranuclear palsy is Richardson syndrome, characterized by levodopa unresponsive symmetric parkinsonism, with a vertical supranuclear gaze palsy, early falls and cognitive impairment. There is currently no detailed understanding of the full sequence of disease pathophysiology in progressive supranuclear palsy. Determining the sequence of brain atrophy in progressive supranuclear palsy could provide important insights into the mechanisms of disease progression, as well as guide patient stratification and monitoring for clinical trials. We used a probabilistic event-based model applied to cross-sectional structural MRI scans in a large international cohort, to determine the sequence of brain atrophy in clinically diagnosed progressive supranuclear palsy Richardson syndrome. A total of 341 people with Richardson syndrome (of whom 255 had 12-month follow-up imaging) and 260 controls were included in the study. We used a combination of 12-month follow-up MRI scans, and a validated clinical rating score (progressive supranuclear palsy rating scale) to demonstrate the longitudinal consistency and utility of the event-based model’s staging system. The event-based model estimated that the earliest atrophy occurs in the brainstem and subcortical regions followed by progression caudally into the superior cerebellar peduncle and deep cerebellar nuclei, and rostrally to the cortex. The sequence of cortical atrophy progresses in an anterior to posterior direction, beginning in the insula and then the frontal lobe before spreading to the temporal, parietal and finally the occipital lobe. This in vivo ordering accords with the post-mortem neuropathological staging of progressive supranuclear palsy and was robust under cross-validation. Using longitudinal information from 12-month follow-up scans, we demonstrate that subjects consistently move to later stages over this time interval, supporting the validity of the model. In addition, both clinical severity (progressive supranuclear palsy rating scale) and disease duration were significantly correlated with the predicted subject event-based model stage (P < 0.01). Our results provide new insights into the sequence of atrophy progression in progressive supranuclear palsy and offer potential utility to stratify people with this disease on entry into clinical trials based on disease stage, as well as track disease progression.

Pathologically Verified Corticobasal Degeneration Mimicking Richardson's Syndrome Coexisting with Clinically and Radiologically Shunt-Responsive Normal Pressure Hydrocephalus.

ABSTRACTBackgroundNormal pressure hydrocephalus (NPH) manifests as gait instability, cognitive impairment, and urinary incontinence. This clinical triad of NPH sometimes occurs with ventriculomegaly in patients with neurodegenerative disease. Patients with pathologically verified neurodegenerative diseases, such as progressive supranuclear palsy (PSP), have received antemortem diagnoses of NPH.ObjectivesThis study presents clinical and pathological features of a patient with pathologically verified corticobasal degeneration (CBD) coexisting with clinically shunt‐responsive NPH.MethodsWe performed clinical, radiological, and pathological evaluations in a patient with CBD whose antemortem diagnosis was PSP Richardson's syndrome (PSP‐RS) coexisting with shunt‐responsive NPH.ResultsA 59‐year‐old woman developed bradykinesia and gait instability and then frequent falls, urinary incontinence, and supranuclear vertical gaze palsy followed. At 63 years of age, her gait disturbance and urinary incontinence had deteriorated rapidly, and cognitive impairment was disclosed. There were typical findings of NPH with ventriculomegaly and disproportionately enlarged subarachnoid space hydrocephalus as well as a 2‐layer appearance with decreased and increased cerebral blood perfusion. Shunt placement ameliorated gait instability for more than 1 year and improved radiological indicators of NPH. However, atrophy of the midbrain progressed with time after transient increases in size. Although the antemortem diagnosis was probable PSP‐RS, pathological evaluation verified CBD. There were severe discontinuities of the ependymal lining of the lateral ventricles and subependymal rarefaction and gliosis with tau‐positive deposition.ConclusionsShunt surgery could ameliorate NPH symptoms in patients with 4‐repeat tauopathies. Careful assessments of clinical findings are necessary to predict the benefits of shunts as a therapeutic option for patients with neurodegenerative diseases coexisting with NPH.

Case Report: Isolated, unilateral oculomotor palsy with anti-GQ1b antibody following COVID-19 vaccination

Neurological complications following vaccinations are extremely rare, but cannot be eliminated. Here, we report the first case of unilateral oculomotor nerve palsy (ONP) with anti-GQ1b antibody after receiving the Pfizer-BioNTech COVID-19 (BNT162b2) mRNA vaccine. A 65-year-old man developed diplopia and ptosis in the right eye 17 days after vaccination, without preceding infection. Neurological examination revealed mild blepharoptosis, limitation of adduction, and vertical gaze on the right side. Increased levels of anti-GQ1b ganglioside antibody in the serum and albuminocytologic dissociation in the cerebrospinal fluid were detected. Cranial magnetic resonance imaging showed swelling and enhancement of the right oculomotor nerve. The patient was diagnosed with right ONP accompanied with anti-GQ1b antibody, and intravenous immunoglobulin (IVIG) therapy for 5 days was administered. The limitation of adduction and vertical gaze improved, and ptosis markedly resolved after IVIG treatment. Given the temporal sequence of disease progression, laboratory findings, and a favorable response to IVIG, a causal relationship cannot be ruled out between the occurrence of ONP and COVID-19 immunization. Since immunomodulatory treatments significantly hasten the recovery and minimize the residual symptoms in anti-GQ1b antibody syndrome, clinicians should be aware of this clinical condition following COVID-19 vaccination.

Genetic and Epigenetic Constructs of Progressive Supranuclear Palsy.

Progressive supranuclear palsy (PSP) is a rapidly progressive primary tauopathy characterized by vertical gaze palsy, postural instability, and mild dementia. PSP shows high clinical and pathologic heterogeneity. Although a few risk factors exist, such as advanced age and environmental toxins, the precise etiology remains largely elusive. Compelling evidence now suggests that genetic background plays a pivotal role in the pathogenetic pathways of PSP. Notably, PSP is genetically and phenotypically a complex disorder. Given the tau pathology, several studies in the past have identified microtubule-associated protein tau (MAPT) gene mutations/variations and its haplotype as the major genetic risk factor of PSP, both in the sporadic and the familial forms. Subsequently, genome-wide association studies (GWAS) also identified several novel risk variants. However, these genetic risk determinants fail to explain the pathogenetic basis of PSP and its phenotypic spectrum in majority of the cases. Some genetic variants are known to confer the risk, while others seem to act as modifier genes. Besides the complex genetic basis of PSP, the pathobiological mechanisms, differential diagnosis, and management of patients with PSP have further been complicated by genetic conditions that mimic the phenotypes of PSP. This is now becoming increasingly apparent that interactions between genetic and environmental factors significantly contribute to PSP development. Further, the effect of environmental factors seems to be mediated through epigenetic modifications. Herein, we provide a comprehensive overview of the genetic and epigenetic constructs of PSP and highlight the relevance of genetic and epigenetic findings in the pathobiology of PSP.

Case report and related comments in a relatively young male patient with right hemiplegia after left thalamo- mesencephalic hemorrhage and a consequent Parinaud syndrome – interdisci-plinary therapeutic – rehabilitative approach

Thalamo- mesencephalic hemorrhage is a devasting event, with a increased morbidity and mor-tality rate. Parinaud’s syndrome, also known as the dorsal midbrain syndrome, is characterized by a supranuclear vertical gaze disturbing, resulting from an insult to the mesencephalic tectum. Matherial and Method. We report the case of a 45-year-old man with personal antecedents of ar-terial hypertension, obesity and type 2 Diabetus mellitus, who was first admitted in the Neuro-logy Clinic Division of the Teaching Emergency Hospital Bucharest with a sudden onset of com-plete right hemiplegia, mixed aphasia and right central– type facial palsy on 17.04.2021, being diagnosed – following complex paraclinic investigations -with a left thalamo- mesencephalic hemorrhage. Results and discusssion. The patient followed a neuro- muscular rehabilitation program in our Neuro- Rehabilitation Clinic Division with favorable outcomes, the case repre-senting a real challenge regarding the complexity of the factors involved. Conclusions. The cli-nical outcomes and the quality of life of patients suffering from thalamo- mesencephalic hemor-rhage depend both on the prompt diagnosis and the efficient treatment, followed by an appro-priate rehabilitation program. Keywords: neuro-rehabilitation, thalamo-mesencephalic hemorrhage, Parinaud syndrome

Quantitative Evaluation of the Association Between Fixation Stability and Phoria During Short-Term Binocular Viewing.

PurposeFixation stability for binocular anomalies with a phoria cannot be detected by direct observations. This study aimed to quantitatively evaluate fixation stability using an eye tracker rather than direct directions in binocular vision with abnormal and normal phorias.MethodsThirty-five and 25 participants with abnormal and normal phoria, respectively, were included in the study. The horizontal and vertical gaze points and convergence were recorded for 10 s using a remote eye tracker while binocularly viewing a target on a display screen 550 mm away. Fixation stability was quantified using bivariate contour ellipse areas (BCEA).ResultsThe fixation stability for all participants-based evaluations as a single cluster in the abnormal phoria group was lower than that in the normal phoria group (p = 0.005). There was no difference between the two groups in the evaluation based on the BCEA for each participant-based evaluation (p = 0.66). Fixation stability was also more related to convergence for the abnormal phoria group than for the normal phoria group (r = 0.769, p < 0.001; r = 0.417, p = 0.038, respectively).ConclusionAs the first study to evaluate fixation stability using an eye-tracker to differentiate between abnormal and normal phoria for non-strabismus, these findings may provide evidence for improving the evaluation of binocular vision not detected with clinical diagnostic tests.

Difficulties in differential diagnosis of chronic tick-borne encephalitis and progressive supranuclear palsy

The article presents two clinical cases of 51 and 57-year-old patients living in regions endemic for tick-borne encephalitis in which the differential diagnosis between progressive supranuclear palsy (PSP) and the extremely rare parkinsonian variant of chronic tick-borne encephalitis (CTBE) resulted in a diagnostic challenge. In both cases there was a clinical presentation of progressive symmetric levodopa-resistant parkinsonism with vertical gaze palsy, cognitive impairment of the executive type, frontal lobe signs, focal dystonia and in one case — early onset of postural instability, which corresponds to the diagnosis of probable PSP. The parkinsonian variant of CTBE was supported by the lack of tick-borne encephalitis virus IgG-antibodies negativity in the blood for several years, intrathecal oligoclonal antibody synthesis in one patient, the absence of typical neuroimaging signs of PSP, and delayed disease onset after a tick bite. Difficulties in diagnosis and possible mechanisms of the pathogenesis of primary progressive CTBE, as well as the similarity of the clinical and pathomorphological presentation of PSP, von Economo encephalitis lethargica, and postencephalitic parkinsonism are discussed.

Unusual progressive supranuclear palsy: A case report

Introduction: Progressive supranuclear palsy (PSP) is a rare brain condition. It is predominantly a sporadic disease that occurs between 45 and 75 years of age, typically after the age of 40. We herein report a presentation of PSP in a 35-year-old male patient. Observation: A 35-year-old man progressively presented gait disturbances with postural instability leading to falls. On examination: Akineto-rigid parkinsonian syndrome (PS), primarily axial, associated with vertical gaze palsy, head backwards tilt and postural instability without tremor. There was a slight frontal syndrome, irritability and dysphagia. The biological assessment (autoimmunity, copper and CSF testing) was correct. Brain MRI of the onset [figure1] did not show mesencephalic atrophy, nor signal abnormalities of overload disorders (Wilson's disease (WD), neuroferritinopathy). The patient underwent a therapeutic test (L-dopa 300 mg/d) over three months, without significant improvement. We then added ropinirole, rivastigmine and paroxetine. Despite the given therapeutics, no remarkable changes were noticed. Discussion: PSP is the most common phenotype of parkinsonism after Parkinson’s disease (PD). Its prevalence estimated to be 5–7 cases /100 000 with peak occurrence at age 63 and no cases recorded before the age of 40. Although neuropathology is the gold standard for diagnosing definite PSP, certain clinical features, such as vertical supranuclear palsy evident in our patient are highly sensitive and specific. It is frequently seen in PSP and has strong relevance. A combination of clinical characteristics with high specificity is used to diagnose probable PSP. Vertical gaze palsy, pseudobulbar palsy, axial rigidity, falls and cognitive dysfunction are PSP’s clinical hallmarks. Our patient clinical presentation strongly suggested probable PSP with Richardson’s syndrome (PSP-RS), which is the commonest PSP presentations. In front of this atypical and sporadic PS, WD was ruled out as well as other differential diagnoses (anti-DPPX encephalitis). A control brain MRI is planned to look for possible midbrain atrophy that may not be found at the disease’s start. The patient clinical features are evocative arguments of the diagnosis, although the onset at the age of 35 is atypical and original. Conclusion: The onset of PSP after the age of 40 is one of the diagnostic requirements so far, however, early presentation should be considered.

Ocular features of patients with Parkinson's disease examined at a Neuro-Optometry Clinic in a tertiary eye care center.

Purpose:To report the ocular features of patients with PD who presented with visual complaints to a tertiary eye care center.Methods:This was a retrospective study carried out between January 2015 and March 2020 at the Neuro-Optometry clinic of a tertiary eye care center in Southern India. All PD patients with ocular complaints examined by the neuro- ophthalmologists were referred to Neuro-Optometry Clinic for detailed evaluation. Patients with other neurodegenerative disorders, brain injury, and other causes of vision loss or extraocular motility disorders were excluded.Results:A total of 43 patients (7 females, 36 males) between 50 and 86 years of age (mean: 70 ± 8.9 years) with a mean duration of PD of 4.5 ± 4.5 years were studied. Decreased vision associated with reading difficulty (40%) was common in PD patients. In terms of gaze restriction, vertical gaze involvement (35%) was more than horizontal involvement (7%). Convergence insufficiency (CI) was the most common binocular vision dysfunction (30%), followed by CI with oculomotor dysfunction (14%) and vertical gaze palsy (18%). Ground prisms were recommended for 26 patients (61%) and home vision therapy for 5 patients (12%) as corrective measures.Conclusion:Binocular vision dysfunction is highly prevalent among PD patients. This could potentially contribute to the reading difficulties and double vision encountered by these patients. Assessment of binocular vision and oculomotor parameters thus becomes important to understand and manage the reading difficulties in patients with PD.

Eye Movement Disorders in Movement Disorders.

Oculomotor assessment is an essential element of the neurological clinical examination and is particularly important when evaluating patients with movements disorders. Most of the brain is involved in oculomotor control, and thus many neurological conditions present with oculomotor abnormalities. Each of the different classes of eye movements and their features can provide important information that can facilitate differential diagnosis. This educational review presents a clinical approach to eye movement abnormalities that are commonly seen in parkinsonism, ataxia, dystonia, myoclonus, tremor, and chorea. In parkinsonism, subtle signs such as prominent square wave jerks, impaired vertical optokinetic nystagmus, and/or the "round the houses" sign suggest early progressive supranuclear gaze palsy before vertical gaze is restricted. In ataxia, nystagmus is common, but other findings such as oculomotor apraxia, supranuclear gaze palsy, impaired fixation, or saccadic pursuit can contribute to diagnoses such as ataxia with oculomotor apraxia, Niemann-Pick type C, or ataxia telangiectasia. Opsoclonus myoclonus and oculopalatal myoclonus present with characteristic phenomenology and are usually easy to identify. The oculomotor exam is usually unremarkable in isolated dystonia, but oculogyric crisis is a medical emergency and should be recognized and treated in a timely manner. Gaze impersistence in a patient with chorea suggests Huntington's disease, but in a patient with dystonia or tremor, Wilson's disease is more likely. Finally, functional eye movements can reinforce the clinical impression of a functional movement disorder.

Clinical disease characteristics of patients with Niemann-Pick Disease Type C: findings from the International Niemann-Pick Disease Registry (INPDR)

BackgroundNiemann-Pick Disease Type C (NPC) is an autosomal recessive rare disease characterised by progressive neurovisceral manifestations. The collection of on-going large-scale NPC clinical data may generate better understandings of the natural history of the disease. Here we report NPC patient data from the International Niemann-Pick Disease Registry (INPDR).MethodThe INPDR is a web-based, patient-led independent registry for the collection of prospective and retrospective clinical data from Niemann-Pick Disease patients. Baseline data from NPC patients enrolled into the INPDR from September 2014 to December 2019 was extracted to analyse the demographic, genetic and clinical features of the disease.ResultsA total of 203 NPC patients from six European countries were included in this study. The mean age (SD) at diagnosis was 11.2 years (14.2). Among enrolled patients, 168 had known neurological manifestations: 43 (24.2%) had early-infantile onset, 47 (26.4%) had late-infantile onset, 41 (23.0%) had juvenile onset, and 37 (20.8%) had adult onset. 10 (5.6%) patients had the neonatal rapidly fatal systemic form. Among the 97 patients with identified NPC1 variants, the most common variant was the c. 3182T > C variant responsible for the p.lle1061Thr protein change, reported in 35.1% (N = 34) of patients. The frequencies of hepatomegaly and neonatal jaundice were greatest in patients with early-infantile and late-infantile neurological onset. Splenomegaly was the most commonly reported observation, including 80% of adult-onset patients. The most commonly reported neurological manifestations were cognitive impairment (78.5%), dysarthria (75.9%), ataxia (75.9%), vertical supranuclear gaze palsy (70.9%) and dysphagia (69.6%). A 6-domain composite disability scale was used to calculate the overall disability score for each neurological form. Across all with neurological onset, the majority of patients showed moderate to severe impairments in all domains, except for ‘swallowing’ and ‘seizure’. The age at diagnosis and death increased with increased age of neurological symptom onset. Miglustat use was recorded in 62.4% of patients and the most common symptomatic therapies used by patients were antiepileptics (32.9%), antidepressants (11.8%) and antacids (9.4%).ConclusionThe proportion of participants at each age of neurological onset was relatively equal across the cohort. Neurological manifestations, such as ataxia, dysphagia, and dysarthria, were frequently observed across all age categories.