Paraneoplastic cochleovestibulopathy: clinical presentations, oncological and serological associations.

OBJECTIVE: Cochleovestibulopathy is a distinguishable paraneoplastic phenotype. In this study, we evaluate clinical presentation, serological/cancer associations and outcomes of paraneoplastic cochleovestibulopathy. METHODS: Retrospective chart review of patients with hearing impairment and/or vestibulopathy who underwent serological evaluations for paraneoplastic antibodies between January 2007 and February 2021 was performed. RESULTS: Twenty-six patients were identified (men, n=23; median age, 45 years, range: 28-70). Biomarkers detected included: KLHL11-IgG| |(n=20,| |77% (coexisting LUZP4-IgG, n=8)),| ||ANNA1-IgG| | |(n=3,| |12%),| |amphiphysin-IgG|| |(n=2,| |8%)| |and| |LUZP4-IgG|| |(n=1,| |4%). Most common neoplastic association was |testicular|/|extra-testicular| |seminoma| | (n=13,| |50%).|| Hearing| impairment (bilateral, 62%) was |present| |in| |all| |patients.| |Fifteen patients (58%) had cochleovestibular dysfunction as their initial presentation before rhombencephalitis/encephalomyelitis manifestations (hearing loss, four; acute vertigo, eight; both, three). |Brain| |MRI| |demonstrated| |internal| |auditory| |canal| |enhancement| |in| |four |patients.| Audiometry commonly revealed severe-profound bilateral sensorineural hearing loss. Most patients |had| a refractory course |despite| |immunotherapy| |and/or| |cancer| |treatment|. CONCLUSION: Cochleovestibulopathy commonly presents with rapidly progressive bilateral hearing loss and/or acute vertigo. However, in some patients, these symptoms present along with or following brainstem/cerebellar manifestations. KLHL11-IgG and seminoma are the most common serological and cancer associations, respectively. Recognition of this phenotype may aid in earlier diagnosis of paraneoplastic autoimmunity and associated cancer.

Hybrid clustering system using Nystagmus parameters discrimination for vestibular disorder diagnosis.

BACKGROUD AND OBJECTIVE: The control of clinical manifestation of vestibular system relies on an optimal diagnosis. This study aims to develop and test a new automated diagnostic scheme for vestibular disorder recognition. METHODS: In this study we stratify the Ellipse-fitting technique using the Video Nysta Gmographic (VNG) sequence to obtain the segmented pupil region. Furthermore, the proposed methodology enabled us to select the most optimum VNG features to effectively conduct quantitative evaluation of nystagmus signal. The proposed scheme using a multilayer neural network classifier (MNN) was tested using a dataset involving 98 patients affected by VD and 41 normal subjects. RESULTS: The new MNN scheme uses only five temporal and frequency parameters selected out of initial thirteen parameters. The scheme generated results reached 94% of classification accuracy. CONCLUSIONS: The developed expert system is promising in solving the problem of VNG analysis and achieving accurate results of vestibular disorder recognition or diagnosis comparing to other methods or classifiers.

Movement disorder in a patient with Human Immunodeficiency Virus on an anti-retroviral therapy: A Case Report.

Human Immunodeficiency Virus associated neurocognitive dysfunction can present as a case of movement disorder in a patient with prolonged antiretroviral therapy. Diagnosis was made after ruling out space occupying lesions, nutritional deficiencies and infectious causes through brain imaging and cerebrospinal fluid analysis. With multidisciplinary care and change of antiretroviral therapy to drugs with higher cerebrospinal fluid penetration, symptoms of the patient improved over a span of six months. Delayed neurological damage due to Human Immunodeficiency Virus can present with isolated cerebellar symptoms.

Ipsilateral Saccade Hypometria and Contralateral Saccadic Pursuit in a Focal Brainstem Lesion: a Rare Oculomotor Pattern.

Eye movement examination may be used to rapidly differentiate peripheral and central vestibular syndromes in patients with acute unsteadiness. The analysis of oculomotor impairments may also support the accurate localization of cerebral lesions, particularly those in the brainstem, that are often loosely defined by cerebral MRIs. Saccades, smooth pursuit, and nystagmus were recorded with video-oculography in a patient who had developed sudden vertigo as a consequence of a focal lesion in the depth of the brachium pontis. The patient had shown a previously unreported pattern of eye movement impairments consisting of (i) ipsilesional hypometric saccades, (ii) contralesional saccadic smooth pursuit, and (iii) unilateral gaze-evoked nystagmus. These symptoms enabled the precise localization of the trajectory of pontocerebellar saccadic tracts in the depth of the brachium pontis. We propose that this rare association resulted from a disruption of cerebellar afferents of saccadic pathways and of cerebellar efferents of horizontal smooth pursuit pathways. This reported case emphasizes the crucial role of careful bedside oculomotor examination in order to discriminate between peripheral and central vestibular syndromes in the diagnosis of sudden vertigo. Moreover, it reveals an exceptional pattern of oculomotor impairments that may allow for the precise localization of the trajectory of cerebellar saccadic afferent pathways in the depth of the brachium pontis.

Finger extension weakness and downbeat nystagmus motor neuron disease syndrome: A novel motor neuron disorder?

INTRODUCTION: Disturbances of eye movements are infrequently encountered in motor neuron diseases (MNDs) or motor neuropathies, and there is no known syndrome that combines progressive muscle weakness with downbeat nystagmus. METHODS: To describe the core clinical features of a syndrome of MND associated with downbeat nystagmus, clinical features were collected from 6 patients. RESULTS: All patients had slowly progressive muscle weakness and wasting in combination with downbeat nystagmus, which was clinically most obvious in downward and lateral gaze. Onset was in the second to fourth decade with finger extension weakness, progressing to other distal and sometimes more proximal muscles. Visual complaints were not always present. Electrodiagnostic testing showed signs of regional motor axonal loss in all patients. DISCUSSION: The etiology of this syndrome remains elusive. Because finger extension weakness and downbeat nystagmus are the discriminating clinical features of this MND, we propose the name FEWDON-MND syndrome. Muscle Nerve 56: 1164-1168, 2017.

Isolated Medial Rectus Palsy: Rare Presentation of Mesencephalon Infarction.

Isolated medial rectus palsy due to mesencephalon lesion is extremely rare. We here describe a patient of midbrain infarction involving the medial rectus subnuclei presenting as isolated medial rectus palsy. Axial diffusion-weighted and coronal T2-weighted magnetic resonance imaging showed acute ischemic lesion in mesencephalon.

The role of MR imaging in investigating isolated pediatric nystagmus.

BACKGROUND: The use of MRI in isolated pediatric nystagmus remains a gray area in clinical management. Many clinicians prefer to order an MRI to rule out intracranial pathology despite the lack of clinically significant findings in most cases. OBJECTIVE: To assess the yield of MR imaging in isolated pediatric nystagmus and define a management algorithm to minimize avoidable MRI referrals and streamline MRI protocols. MATERIALS AND METHODS: We reviewed the charts of 148 children who underwent neuro MRI for isolated nystagmus between January 2008 and September 2014. We noted nystagmus onset and clinical characteristics and compared them with the MRI features and visual electrophysiology results. RESULTS: We included 85 boys and 63 girls (total 148, average age at MRI 4.24 ± 4.19 years). Twenty-three (15.5%) children had abnormal intracranial findings on MRI including abnormal signal lesions (4.1%; n=6), Chiari I malformations (3.4%; n=5) and optic pathway glioma (2.0%; n=3). The time of onset of nystagmus was not associated with an abnormal MRI (P=0.2). Seventy children underwent visual electrophysiology testing but this test could not predict abnormality at MRI, either (P=0.12). CONCLUSION: Among children with isolated nystagmus, 15.5% had abnormalities on neuroimaging. Neither clinical characteristics of nystagmus nor the visual electrophysiology results allowed prediction of intracranial pathology. We were unable to formulate a management algorithm for the optimal sequence of investigations (MRI preceding visual electrophysiology or vice versa), but we discuss the use of gadolinium contrast agent and orbital sequences in isolated pediatric nystagmus.

Midbrain lesion-induced disconjugate gaze: a unifying circuit mechanism of ocular alignment?

BACKGROUND: Disconjugate eye movements are essential for depth perception in frontal-eyed species, but their underlying neural substrates are largely unknown. Lesions in the midbrain can cause disconjugate eye movements. While vertically disconjugate eye movements have been linked to defective visuo-vestibular integration, the pathophysiology and neuroanatomy of horizontally disconjugate eye movements remains elusive. METHODS: A patient with a solitary focal midbrain lesion was examined using detailed clinical ocular motor assessments, binocular videooculography and diffusion-weighted MRI, which was co-registered to a high-resolution cytoarchitectonic MR-atlas. RESULTS: The patient exhibited both vertically and horizontally disconjugate eye alignment and nystagmus. Binocular videooculography showed a strong correlation of vertical and horizontal oscillations during fixation but not in darkness. Oscillation intensities and waveforms were modulated by fixation, illumination, and gaze position, suggesting shared visual- and vestibular-related mechanisms. The lesion was mapped to a functionally ill-defined area of the dorsal midbrain, adjacent to the posterior commissure and sparing nuclei with known roles in vertical gaze control. CONCLUSION: A circumscribed region in the dorsal midbrain appears to be a key node for disconjugate eye movements in both vertical and horizontal planes. Lesioning this area produces a unique ocular motor syndrome mirroring hallmarks of developmental strabismus and nystagmus. Further circuit-level studies could offer pivotal insights into shared pathomechanisms of acquired and developmental disorders affecting eye alignment.

Geometrical and volume changes of the membranous vestibular labyrinth in guinea pigs with endolymphatic hydrops.

OBJECTIVE: To evaluate geometrical and volume changes of membranous vestibular labyrinths in guinea pigs after endolymphatic hydrops (EH). METHODS: The membranous labyrinths of normal guinea pigs and of those with EH for 4 and 8 weeks were reconstructed after being scanned using micro-computed tomography subseqent to being stained in osmium tetroxide (OsO4). The diameters and volumes of the semicircular ducts, ampullae, utricles and saccules were measured based on the three-dimensional models. RESULTS: The diameters of the ampullae and utricles of EH guinea pigs were greater than those of the normal guinea pigs, while there were no significant differences in the diameters of the semicircular ducts among all groups. The volumes of ampullae, utricles and saccules of the EH groups were greater than those of the control group, but there were no changes in volumes of semicircular ducts after EH. CONCLUSION: The dilations of the membranous vestibular labyrinth in guinea pigs with EH mainly occur at the ampullae, utricles and saccules.

Generalized vestibular hyporeflexia and chronic upbeat nystagmus due to thiamine deficiency.

BACKGROUND: Ocular motor and vestibular manifestations of Wernicke's thiamine deficiency (WTD) are frequent and heterogeneous. Previous neuropathological and neuroimaging findings identified brainstem and cerebellar lesions responsible for these findings, however, peripheral vestibular lesions are probably uncommon in human WTD, though noted on an avian thiamine deficient study. MATERIAL: Single case study of a WTD patient post-gastric bypass who developed ataxia, oscillopsia and nystagmus, with low serum thiamine, and increased MRI T2 signal in the thalami, but normal brainstem and cerebellum. Vestibular evaluation showed significant vestibular hyporreflexia affecting all six canals, and a chronic upbeat nystagmus, now for 14 months after WTD onset. METHODS: Serial clinical, video head impulse, nystagmus analysis, cervical and ocular vestibular evoked responses. She is undergoing treatment with Memantine, Clonazepam and vestibular rehabilitation, and feels improvement. CONCLUSION: This report shows a novel combination of central and peripheral vestibular findings, of relevance for diagnosis and treatment, in addition to the development of a coherent hypothesis on the ocular motor and vestibular findings in WTD.

Incidence, characteristics, and neuroanatomical substrates of vestibular symptoms in supratentorial stroke.

The incidence and characteristics of acute vestibular symptoms, responsible structures, and lateralization of the causative lesions in supratentorial stroke remain unknown. This study aimed to determine the incidence, clinical features, and anatomical correlation of acute vestibular symptoms in supratentorial stroke. We performed a prospective, multicenter, observational study that had recruited patients with supratentorial stroke from the neurology clinics of referral-based four university hospitals in Korea. All patients received a constructed neuro-otological evaluations, and neuroimaging. We analyzed the incidence of acute vestibular symptoms, abnormal ocular motor and vestibular function tests, and stroke lesions. Of 1301 patients with supratentorial stroke, 48 (3.7%) presented with acute vestibular symptoms, and 13 of them (1%) had the vestibular symptoms in isolation. In patients with acute vestibular symptoms, abnormal findings included spontaneous nystagmus (5%), impaired horizontal smooth pursuit (41%), and abnormal tilt of the subjective visual vertical (SVV) (20%). Video head impulse and caloric tests were normal in all the patients. There was no clear correlation between acute vestibular symptoms and involvement of specific vestibular cortex. In patients with unilateral stroke, there was also no lateralization of the causative lesions of acute vestibular symptoms (left vs. right; 52 vs. 48%), even in patients with vertigo (left vs. right; 58 vs. 42%). This study demonstrates that the incidence of acute vestibular symptoms in supratentorial stroke is 3.7%, with being isolated in 1%. The widespread lesions responsible for acute vestibular symptoms implicate diffuse multisensory cortical-subcortical networks in the cerebral hemispheres without a lateralization.