Scale for Ocular Motor Disorders in Ataxia (SODA) in Patients with Multiple System Atrophy.

A clinical scale fully dedicated to evaluating ocular motor abnormalities is required for now. We investigated the utility of a recently developed Scale for Ocular motor Disorders in Ataxia (SODA) in patients with multiple system atrophy (MSA). We prospectively assessed SODA in consecutive patients with MSA between August 2021 and August 2023 at the Korea University Medical Center. The results of the clinical exam-based SODA were compared with those measured using video-oculography (VOG-guided SODA). We also compared the findings with other established clinical scales targeting patients with MSA, including the Unified Multiple System Atrophy Rating Scale (UMSARS) I-II, Movement Disorder Society-Unified Parkinson's Disease Rating Scale motor part (UPDRS-III), Scale for Assessment of Rating of Ataxia (SARA), Composite Autonomic Symptom Score-31 (COMPASS-31), and Composite Autonomic Severity Score (CASS). Twenty patients were enrolled in our study (17 with cerebellar-type MSA and three with Parkinson-type MSA). Scores ranged from 1 to 14 (median [interquartile range (IQR)] = 8 [5-10]). Among the subscales, saccades had a median score of 2.5 (IQR = 1-3), followed by ocular pursuit (1 [0-1]), nystagmus (1 [0-2]), saccadic intrusions (1 [0-1]), vestibulo-ocular reflex (VOR) (0.5 [0-1]), ocular alignment (0 [0-1]), and VOR cancellation (1 [0-1]). The clinical-exam-based SODA (p = 0.020) and VOG-guided SODA (p = 0.034) positively correlated with disease duration. No correlation was found between clinical exam-based SODA and other scales. Skew deviation, gaze-evoked nystagmus, VOR cancellation, and smooth pursuit had the highest precision among the items. Ocular misalignment and spontaneous and positional nystagmus were frequently false positive and were poorly detected with clinical exam-based SODA. Six patients with repeated evaluation exhibited higher scores, along with deterioration documented on other clinical scales. The SODA can reliably predict neurodegeneration as an additional clinical surrogate in MSA.

Successful use of tacrolimus for treatment-refractory neuroblastoma-associated opsoclonus-myoclonus-ataxia syndrome: A case series.

Opsoclonus-myoclonus-ataxia syndrome (OMAS) is an autoimmune central nervous system disorder, primarily manifesting as a paraneoplastic sequalae to neuroblastoma, and characterized by motor disorders and behavioral disturbances. OMAS is typified by aberrant B-cell and T-cell activation. Current treatment involves immunosuppression using corticosteroids, intravenous immunoglobulin, and rituximab. However, these approaches often lead to treatment-related toxicities and symptomatic recurrences with chronic neurocognitive impairment. We treated three children with refractory neuroblastoma-associated OMAS with tacrolimus, a T-cell-targeting calcineurin inhibitor, effectively controlling symptoms within a month and enabling the discontinuation of immunosuppression with minimal side effects. Tacrolimus shows promise as a therapeutic option for refractory OMAS.

Comparison of Visual Symptom Frequency and Occupational Issues Between Patients With and Without Concussion.

IMPORTANCE: Occupational therapy practitioners' knowledge of and advocacy for clients with visual symptoms postconcussion can have a considerable impact on recovery. OBJECTIVE: To compare the frequency of vision symptoms and occupational performance deficits in a sample of participants with and without concussion. DESIGN: Cross-sectional study. SETTING: Sports medicine clinic. PARTICIPANTS: Adolescents and adults with concussion (n = 20) and musculoskeletal injuries (n = 19). OUTCOMES AND MEASURES: Measures included monocular amplitude of accommodation, near point of convergence, Binocular Vision Assessment (BVA) computerized screening for phoria, BVA computerized screening for fusional vergence, the Developmental Eye Movement Test, the Canadian Occupational Performance Measure, and the Convergence Insufficiency Symptom Survey-Concussion Version (CISS-CON). RESULTS: We found significant differences between participants with and without concussion using the CISS-CON (p = .001), positive fusional vergence (p = .02), and near point of convergence (p = .02). Participants with concussion scoring above cutoffs on multiple measures reported poorer performance (p = .005) and satisfaction (p = .004) with valued occupations. CONCLUSIONS AND RELEVANCE: Concussion has a detrimental effect on vision and occupation, and occupational therapy practitioners are well-positioned to assess and address issues arising from this relationship. Plain-Language Summary: Vision symptoms commonly experienced after a concussion are associated with reduced occupational performance and satisfaction and can have a considerable impact on recovery. Occupational therapy assessment for clients with concussion should include screening for vision difficulties.

Retrospective analysis of COVID-19 patients with Guillain-Barre, Miller-Fisher, and opsoclonus-myoclonus-ataxia syndromes-a case series.

BACKGROUND: In accordance with the rising number of SARS-CoV­2 infections, reports of neurological complications have also increased. They include cerebrovascular diseases but also immunological diseases such as Guillain-Barre syndrome (GBS), Miller-Fisher syndrome (MFS), and opsoclonus-myoclonus-ataxia syndrome (OMAS). While GBS and MFS are typical postinfectious complications, OMAS has only recently been described in the context of COVID-19. GBS, MFS, and OMAS can occur as para- and postinfectious, with different underlying pathomechanisms depending on the time of neurological symptom onset. The study aimed to describe clinical features, time between infection and onset of neurological symptoms, and outcome for these diseases. METHODS: All COVID-19 patients treated in the neurological ward between January 2020 and December 2022 were screened for GBS, MFS, and OMAS. The clinical features of all patients, with a particular focus on the time of onset of neurological symptoms, were analyzed. RESULTS: This case series included 12 patients (7 GBS, 2 MFS, 3 OMAS). All GBS and one MFS patient received immunomodulatory treatment. Three patients (2 GBS, 1 OMAS) had a severe COVID-19 infection and received mechanical ventilation. In patients with OMAS, only one patient received treatment with intravenous immunoglobulin and cortisone. The remaining two patients, both with disease onset concurrent with SARS-COV­2 infection, recovered swiftly without treatment. In all subgroups, patients with concurrent onset of neurological symptoms and COVID-19 infection showed a trend toward shorter disease duration. CONCLUSION: All patient groups displayed a shorter disease duration if the onset of neurological symptoms occurred shortly after the COVID-19 diagnosis. In particular, both the OMAS patients with symptom onset concurrent with COVID-19 showed only abortive symptoms followed by a swift recovery. This observation would suggest different pathomechanisms for immune-mediated diseases depending on the time of onset after an infection.

Pendular Oscillation and Ocular Bobbing After Pontine Hemorrhage.

The pathophysiology of acute, vertical spontaneous eye movements following pontine hemorrhage is not well understood. Here, we present and discuss the video-oculography findings of a patient with acute pontine hemorrhage who developed vertical pendular oscillation and ocular bobbing while comatose. The amplitudes, peak velocities, frequency distribution, and phase planes (velocity versus position) of the eye movements were analyzed. The vertical pendular oscillation was rhythmic with a peak frequency of 1.7 Hz, but amplitudes (mean 1.9°, range 0.2-8.2°) and peak velocities (mean 20.6°/s; range 5.9-60.6°/sec) fluctuated. Overall, their peak velocities were asymmetric, faster with downward than upward. Higher peak velocities were seen with larger amplitudes (downward phase r = 0.95, p < 0.001; upward phase r = 0.91, p < 0.001) and with movements beginning at eye positions lower in the orbit (downward phase r = - 0.64, p < 0.001; upward phase r = - 0.86, p < 0.001). Interspersed were typical ocular bobbing waveforms with a fast (peak velocity 128.8°/s), large-amplitude (17.5°) downward movement, sometimes followed by a flat interphase interval (0.5 s) when the eye was nearly stationary, and then a slow return to mid-position with a decaying velocity waveform. To account for the presence and co-existence of pendular oscillations and bobbing, we present and discuss three hypothetical models, not necessarily mutually exclusive: (1) oscillations originating in the inferior olives due to disruption of the central tegmental tract(s); (2) unstable neural integrator function due to pontine cell group damage involving neurons involved in gaze-holding; (3) low-frequency saccadic intrusions following omnipause neuron damage.

Eye movement abnormalities are associated with brainstem atrophy in Wilson disease.

BACKGROUNDS: This study aims to characterize eye movement abnormalities in Wilson disease and examine their association with the degree of brainstem atrophy. METHODS: Twenty patients (10 males, mean age 46.8, SD 8.9 years) with genetically confirmed neurological WD on stable anti-copper treatment and 20 age- and sex-matched healthy subjects were examined. Eye movements, including prosaccade and antisaccade tasks, were evaluated using infrared videooculography. MRI was performed using 1.5 T system, and T2-weighted images were used for the measurement of midbrain and pontine area on mid-sagittal slices. Clinical severity was assessed using the Unified Wilson's Disease Rating Scale (UWDRS). RESULTS: Compared to healthy controls, WD patients showed prolonged latencies of horizontal prosaccades and hypometry of both horizontal (p = 0.04) and vertical (p = 0.0046) prosaccades. In the antisaccade task, WD patients showed prolonged latency of both horizontal (p = 0.04) and vertical antisaccades (p = 0.047) and increased error rate of vertical antisaccades (p = 0.04). There is a significant association between midbrain area and horizontal latencies (r = -0.53; p = 0.02) and vertical maximum speed in prosaccades (r = 0.47; p = 0.04). The pons area inversely correlated with horizontal prosaccade and antisaccade latencies (p = 0.007). CONCLUSIONS: We showed impairments of ocular saccades such as prolonged latencies, hypometry, and increased error rate in antisaccades. The strong association between prolonged latencies of prosaccades and the brainstem atrophy suggests that VOG might serve as a sensitive electrophysiological marker of brainstem dysfunction in WD.

Monocular Diplopia and Nondisplaced Inferior Rectus Muscle on Computed Tomography in a Pediatric Pure Orbital-Floor Fracture.

Trapdoor fractures are common in children because of elastic nature of the pediatric bone. Clinical signs and radiological evidence in these cases may be minimal.This study involves a 14-year-old girl who sustained blunt trauma to her left eye. Initial investigation, for pure orbital floor fracture included computerized tomography (CT scan) of the orbit, did not show any evidence of incarcerated rectus muscle. She had no limitation of extraocular movements nor enophthalmos. Following conservative treatment, she had a left persistent orbital pain and left monocular diplopia. This prompted a magnetic resonance imaging (MRI) of the orbit investigating soft tissue, which found fine partial muscle herniation through the self-sealed fracture needing surgical intervention.Although an orbital CT imaging is preferrd, in this acute setting, magnetic resonance imaging should be considered to delineate the soft tissue anatomy in relation to a trapdoor fracture, especially when there are not cardinal associated physical symptoms with a trap door fracture such as restricted eye movement and enophthalmos. Mono-ocular diplopia can be noted as an associated symptom to prompt early surgical repair.

Ocular neuromyotonia.

Ocular neuromyotonia is a rare, albeit treatable, ocular motor disorder, characterised by recurrent brief episodes of diplopia due to tonic extraocular muscle contraction. Ephaptic transmission in a chronically damaged ocular motor nerve is the possible underlying mechanism. It usually improves with carbamazepine. A 53-year-old woman presented with a 4-month history of recurrent episodes of binocular vertical diplopia (up to 40/day), either spontaneously or after sustained downward gaze. Between episodes she had a mild left fourth nerve palsy. Sustained downward gaze consistently triggered downward left eye tonic deviation, lasting around 1 min. MR scan of the brain was normal. She improved on starting carbamazepine but developed a rash that necessitated stopping the drug. Switching to lacosamide controlled her symptoms.

Parinaud syndrome: Any clinicoradiological correlation?

INTRODUCTION: The significance of MRI findings of patients with Parinaud syndrome (PS) with respect to clinical characteristics is poorly defined. Over the past decades, all patients with PS undergo magnetic resonance imaging which allows a better identification of the lesion localization. We compared the neuro-ophthalmological findings of patients with PS caused by intrinsic (intra-axial) vs extrinsic (pineal gland tumor) brainstem lesions. METHODS: Medical records of patients with PS evaluated between 2000 and 2016 were retrospectively reviewed. RESULTS: Twenty-six patients with PS were included. Eight patients had pineal gland tumors and hydrocephalus. Two patients had hydrocephalus due to aqueduct stenosis and fourth ventricle tumor. Sixteen patients suffered from an intrinsic brainstem lesion and seven associated with hydrocephalus. The neuro-ophthalmological findings did not differ between patients with extrinsic and intrinsic brainstem lesions. No correlation was found between the grade of hydrocephalus and number of clinical findings except for more findings in low-grade hydrocephalus in intrinsic (40%) vs extrinsic (0%) lesions (P=.003). Patients with moderate brainstem lesions and hydrocephalus had more clinical findings (65%) than patients with the same grade of brainstem involvement without hydrocephalus (29%) (P=.03). The resolution rate of ophthalmological findings was comparable in all groups of patients. CONCLUSIONS: Our results did not show differences in neuro-ophthalmological findings between intra- and extra-axial lesions causing PS. However, the presence of hydrocephalus was an important factor influencing clinical findings. The prognosis of PS was less favorable than generally reported.

Strabismus and Micro-Opsoclonus in Machado-Joseph Disease.

We describe novel deficits of gaze holding and ocular alignment in patients with spinocerebellar ataxia type 3, also known as Machado-Joseph disease (MJD). Twelve MJD patients were studied. Clinical assessments and quantitative ocular alignment measures were performed. Eye movements were quantitatively assessed with corneal curvature tracker and video-oculography. Strabismus was seen in ten MJD patients. Four patients had mild to moderate intermittent exotropia, three had esotropia, one had skew deviation, one had hypotropia, and one patient had moderate exophoria. Three strabismic patients had V-pattern. Near point of convergence was normal in two out of three patients with exotropia. Gaze holding deficits were also common. Eight patients had gaze-evoked nystagmus, and five had micro-opsoclonus. Other ocular motor deficits included saccadic dysmetria in eight patients, whereas all had saccadic interruption of smooth pursuit. Strabismus and micro-opsoclonus are common in MJD. Coexisting ophthalmoplegia or vergence abnormalities in our patients with exotropia that comprised 50 % of the cohort could not explain the type of strabismus in our patients. Therefore, it is possible that involvement of the brainstem, the deep cerebellar nuclei, and the superior cerebellar peduncle are the physiological basis for exotropia in these patients. Micro-opsoclonus was also common in MJD. Brainstem and deep cerebellar nuclei lesion also explains micro-opsoclonus, whereas brainstem deficits can describe slow saccades seen in our patients with MJD.

People with diabetic peripheral neuropathy display a decreased stepping accuracy during walking: potential implications for risk of tripping.

AIM: To examine the stepping accuracy of people with diabetes and diabetic peripheral neuropathy. METHODS: Fourteen patients with diabetic peripheral neuropathy (DPN), 12 patients with diabetes but no neuropathy (D) and 10 healthy non-diabetic control participants (C). Accuracy of stepping was measured whilst the participants walked along a walkway consisting of 18 stepping targets. Preliminary data on visual gaze characteristics were also captured in a subset of participants (diabetic peripheral neuropathy group: n = 4; diabetes-alone group: n = 4; and control group: n = 4) during the same task. RESULTS: Patients in the diabetic peripheral neuropathy group, and patients in the diabetes-alone group were significantly less accurate at stepping on targets than were control subjects (P < 0.05). Preliminary visual gaze analysis identified that patients diabetic peripheral neuropathy were slower to look between targets, resulting in less time being spent looking at a target before foot-target contact. CONCLUSIONS: Impaired motor control is theorized to be a major factor underlying the changes in stepping accuracy, and potentially altered visual gaze behaviour may also play a role. Reduced stepping accuracy may indicate a decreased ability to control the placement of the lower limbs, leading to patients with neuropathy potentially being less able to avoid observed obstacles during walking.

Psychogenic Ophthalmologic Movement Disorders.

In this study, the authors retrospectively identified 11 patients with psychogenic ophthalmologic movement disorders (POMDs) (6%) among 182 patients with psychogenic movement disorders (PMDs), using medical charts and video reviews. The phenomenology included oculogyric crises (N=7), opsoclonus (N=5), and ocular flutter (N=1). No statistically significant differences were observed in gender and PMD distribution between patients with and without POMDs, although a trend for younger age at onset was observed in patients with POMDs. Seven patients showed improvement with psychotherapy, whereas two patients with persistent ocular supraversion and blepharospasm failed to improve. Based on our own series and review of literature, we conclude that POMDs contribute to the overall morbidity in patients affected with PMDs.

Eye movement and vestibular dysfunction in mitochondrial A3243G mutation.

Studying eye movements and vestibular function would provide insights into brain networks that are vulnerable in mitochondrial disorders. We sought eye movement and vestibular abnormalities in three Korean patients with a mitochondrial A3243G point mutation. The patients suffered from vertigo and imbalance during the stroke-like and seizure episodes from lesions involving the posterior cerebral cortex, which were accompanied by bilateral saccadic hypermetria and horizontal gaze-evoked nystagmus. Furthermore, two patients showed bilateral impairments of the vestibulo-ocular reflex during head impulses for the horizontal and posterior canals on both sides in the absence of caloric paresis. Cerebellar atrophy was prominent on MRIs in two patients and was less marked in the other patient. These findings imply that the cerebellum is susceptible to neuronal energy deficiency due to mitochondrial A3243G point mutation.

Isolated unilateral infarction of the cerebellar tonsil: ocular motor findings.

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.

A novel treatment-responsive encephalitis with frequent opsoclonus and teratoma.

Among 249 patients with teratoma-associated encephalitis, 211 had N-methyl-D-aspartate receptor antibodies and 38 were negative for these antibodies. Whereas antibody-positive patients rarely developed prominent brainstem-cerebellar symptoms, 22 (58%) antibody-negative patients developed a brainstem-cerebellar syndrome, which in 45% occurred with opsoclonus. The median age of these patients was 28.5 years (range = 12-41), 91% were women, and 74% had full recovery after therapy and tumor resection. These findings uncover a novel phenotype of paraneoplastic opsoclonus that until recently was likely considered idiopathic or postinfectious. The triad of young age (teenager to young adult), systemic teratoma, and high response to treatment characterize this novel brainstem-cerebellar syndrome.

Genetic and phenotypic diversity of NHE6 mutations in Christianson syndrome.

OBJECTIVE: Recently, Christianson syndrome (CS) has been determined to be caused by mutations in the X-linked Na(+) /H(+) exchanger 6 (NHE6). We aimed to determine the diagnostic criteria and mutational spectrum for CS. METHODS: Twelve independent pedigrees (14 boys, age = 4-19 years) with mutations in NHE6 were administered standardized research assessments, and mutations were characterized. RESULTS: The mutational spectrum was composed of 9 single nucleotide variants, 2 indels, and 1 copy number variation deletion. All mutations were protein-truncating or splicing mutations. We identified 2 recurrent mutations (c.1498 c>t, p.R500X; and c.1710 g>a, p.W570X). Otherwise, all mutations were unique. In our study, 7 of 12 mutations (58%) were de novo, in contrast to prior literature wherein mutations were largely inherited. We also report prominent neurological, medical, and behavioral symptoms. All CS participants were nonverbal and had intellectual disability, epilepsy, and ataxia. Many had prior diagnoses of autism and/or Angelman syndrome. Other neurologic symptoms included eye movement abnormalities (79%), postnatal microcephaly (92%), and magnetic resonance imaging evidence of cerebellar atrophy (33%). Regression was noted in 50%, with recurrent presentations involving loss of words and/or the ability to walk. Medical symptoms, particularly gastrointestinal symptoms, were common. Height and body mass index measures were below normal ranges in most participants. Behavioral symptoms included hyperkinetic behavior (100%), and a majority exhibited high pain threshold. INTERPRETATION: This is the largest cohort of independent CS pedigrees reported. We propose diagnostic criteria for CS. CS represents a novel neurogenetic disorder with general relevance to autism, intellectual disability, Angelman syndrome, epilepsy, and regression.

Unilateral internuclear ophthalmoplegia as an isolated presentation of metastatic melanoma.

Multiple sclerosis in younger patients and brainstem infarction in the elderly are the most common causes of internuclear ophthalmoplegia (INO). We report unilateral INO as the isolated clinical manifestation of a large, solitary, metastatic melanoma in the pons. Brain metastasis can present as INO.

Concomitant Idiopathic Orbital Inflammatory Pseudotumor and Thyroid-Associated Ophthalmopathy.

PURPOSE: Coexistence of idiopathic orbital inflammatory pseudotumor (IOIP) and thyroid-associated ophthalmopathy (TAO) is extremely rare. The purpose of this article is to analyze the clinical features, image findings, and therapeutic outcomes of concomitant IOIP and TAO in China. MATERIALS AND METHODS: Detailed clinical records of 3 Chinese patients with concomitant IOIP and TAO were reviewed, including their clinical history, symptoms and signs, ultrasonography, computed tomography (CT), and steroid therapy. RESULTS: Among the 3 patients, were 2 men and 1 woman, aged 42, 49, and 48 years, respectively. The right orbit was involved in 1 patient and both orbits in 2 patients. In addition to showing the typical features of TAO, such as hyperthyroidism, upper eyelid retraction, and enlarged extraocular muscles with tendon sparing, all 3 patients showed ambiguous soft tissue masses in one or both orbits. Pathologic examination after biopsy of the mass in 1 patient confirmed the diagnosis of lymphatic IOIP. All the patients responded extremely well to steroid treatment. CONCLUSIONS: Although rare, a simultaneous coexistence of IOIP and TAO can occur. Therefore, it is important for clinicians to be aware of the potential for concomitant IOIP and TAO.

Anomalous head posture related to visual problems.

The cause of the anomalous head posture (AHP) has been mainly assigned to ocular, orthopedic, and neurologic causes. The AHP can take the form of head tilt, face turn, chin up, chin down, or combined, depending on the specific etiology. However, there are many variations, and the type of the head posture cannot reliably predict the underlying cause. Ocular AHP is usually an attempt to improve visual acuity or binocularity. Since the etiology is not always obvious, we stress that these patients must be carefully evaluated by ophthalmologists. Our effort here is to offer the neurologist a thorough insight in the specific head posture pattern primarily related to visual disorders.

[Clinical analysis of thyroid associated ophthalmopathy with myasthenia Graves in 12 patients].

OBJECTIVE: To summarized the clinical features of thyroid associated ophthalmopathy patients with myasthenia gravis. METHODS: This is a retrospective case series study. The clinical data of 12 thyroid associated ophthalmopathy patients with myasthenia gravis were collected in the 416 Hospital of Nuclear Industry from Oct. 2012 to Feb. 2014. All patients had a detailed medical history including symptoms of onset, the best corrected visual acuity, anterior and posterior segment examination, the exophthalmos, eyelid position, eye movement, diplopia, strabismus, systemic symptoms, concurrent fatigue test, neostigmine test, thyroid function and orbital CT scan. One patient underwent CT examination of thymus. RESULTS: In all 12 patients, there were 8 females and 4 males with age from 13.0 to 44.0 years (the median age of 26.5 years), 11 cases had difficulties to open their eyes which was least severe in the morning and worsened in the evening. All of cases did not have general symptoms. Ptosis was observed in 9 cases, 3 cases were bilateral, and 6 cases were unilateral. Abnormal extra ocular muscle function was observed in 8 cases, all of them were bilateral. In these 16 eyes, the limitation of downward gaze were observed in 15 eyes, the limitation of upward, outward and inward gaze were observed in 14 eyes, eye fixation occurred in 4 eyes. Four cases had diplopia, 3 cases had strabismus, and 2 of them were exotropia. Orbital CT demonstrated extraocular muscle thickening in 6 cases. Thickening of inferior rectus were observed in all 12 eyes, superior rectus and medial rectus were found thickened in 6 eyes, and thickening of lateral rectus muscle was found in 3 eyes. CONCLUSIONS: The clinical features of thyroid associated ophthalmopathy patients with myasthenia gravis were complex. When ptosis and eye movement disorders were not consistent with TAO severity, associating with exotropia and systemic muscle paralysis, myasthenia gravis should be considered.