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Downbeat nystagmus (DBN) is the most common form of acquired central vestibular nystagmus. Gravity perception in patients with DBN has previously been investigated by means of subjective visual straight ahead (SVA) and subjective visual vertical (SVV) in the pitch and roll planes only during whole-body tilts. To our knowledge, the effect of head tilt in the roll plane on the SVV and on DBN has not yet been systematically studied in patients. In this study, we investigated static and dynamic graviceptive function in the roll-plane in patients with DBN (patients) and healthy-controls (controls) by assessment of the Subjective Visual Vertical (SVV) and the modulation of slow-phase-velocity (SPV) of DBN. SPV of DBN and SVV were tested at different head-on trunk-tilt positions in the roll-plane (0°,30° clockwise (cw) and 30° counterclockwise (ccw)) in 26 patients suffering from DBN and 13 controls. In patients, SPV of DBN did not show significant modulations at different head-tilt angles in the roll-plane. SVV ratings did not differ significantly between DBN patients vs. controls, however patients with DBN exhibited a higher variability in mean SVV estimates than controls. Our results show that the DBN does not exhibit any modulation in the roll-plane, in contrast to the pitch-plane. Furthermore, patients with DBN show a higher uncertainty in the perception of verticality in the roll-plane in form of a higher variability of responses. [ABSTRACT FROM AUTHOR]

Purpose of Review: Downbeat nystagmus (DBN) and cerebellar ataxia present significant challenges in shared clinical management. This review article examines current treatment options for both disorders, focusing on their shared mechanisms, efficacy, and patient outcomes. We include evidence from recent studies on pharmacological interventions, including the use of muscle relaxants and central nervous system (CNS) acting sedatives, as well as non-pharmacological approaches such as vestibular rehabilitation. Recent Findings: We explore emerging treatments, including novel ion channel modulators and cerebellar stimulation, highlighting their potential benefits and limitations. By integrating findings from various sources, we aim to provide a detailed overview of the state-of-the-art therapies and offer guidance for clinicians in tailoring individualized treatment plans. Summary: The review underscores the need for continued research to improve therapeutic outcomes and enhance the quality of life for patients affected by DBN and cerebellar ataxia. [ABSTRACT FROM AUTHOR]

The cerebellum is important for motor adaptation. Lesions to the vestibulo-cerebellum selectively cause gait ataxia. Here we investigate how such damage affects locomotor adaptation when performing the 'broken escalator' paradigm. Following an auditory cue, participants were required to step from the fixed surface onto a moving platform (akin to an airport travellator). The experiment included three conditions: 10 stationary (BEFORE), 15 moving (MOVING) and 10 stationary (AFTER) trials. We assessed both behavioural (gait approach velocity and trunk sway after stepping onto the moving platform) and neuromuscular outcomes (lower leg muscle activity, EMG). Unlike controls, cerebellar patients showed reduced after-effects (AFTER trials) with respect to gait approach velocity and leg EMG activity. However, patients with cerebellar damage maintain the ability to learn the trunk movement required to maximise stability after stepping onto the moving platform (i.e., reactive postural behaviours). Importantly, our findings reveal that these patients could even initiate these behaviours in a feedforward manner, leading to an after-effect. These findings reveal that the cerebellum is crucial for feedforward locomotor control, but that adaptive locomotor behaviours learned via feedback (i.e., reactive) mechanisms may be preserved following cerebellum damage. [ABSTRACT FROM AUTHOR]

Downbeat nystagmus (DBN) is a neuro-otological finding frequently encountered by clinicians dealing with patients with vertigo. Since DBN is a finding that should be understood because of central vestibular dysfunction, it is necessary to know how to frame it promptly to suggest the correct diagnostic-therapeutic pathway to the patient. As knowledge of its pathophysiology has progressed, the importance of this clinical sign has been increasingly understood. At the same time, clinical diagnostic knowledge has increased, and it has been recognized that this sign may occur sporadically or in association with others within defined clinical syndromes. Thus, in many cases, different therapeutic solutions have become possible. In our work, we have attempted to systematize current knowledge about the origin of this finding, the clinical presentation and current treatment options, to provide an overview that can be used at different levels, from the general practitioner to the specialist neurologist or neurotologist. [ABSTRACT FROM AUTHOR]

Objective: To investigate the topical diagnosis, possible etiology and mechanism of spontaneous downbeat nystagmus (sDBN) patients with dizziness/vertigo. Methods: The clinical features of dizziness/vertigo patients accompanied with DBN were retrospectively reviewed in the Vertigo Center of our hospital from January 2018 to March 2021. The clinical features of dizziness/vertigo patients accompanied with DBN were reviewed. Comprehensive VNG, bithermal caloric testing, video-head-impulse test (vHIT), vestibular-evoked myogenic potentials (VEMP), head magnetic resonance imaging (MRI), three-dimensional fluidattenuated incersion recovery magnetic resonance imaging (3D-FLAIR MRI) in the inner ear, serum immunology and other examinations were to determine the lesion site, and analyze its possible etiology and mechanism. Results: A total of 54 patients were included. Among them, 70.4% (n = 38) of DBN patients were diagnosed with episodic vestibular syndrome (EVS), 22.2% (n = 12) with chronic vestibular syndrome (CVS), and 7.4% (n = 4) with acute vestibular syndrome (AVS). Among all the patients, 51.9% of DBN patients had clear etiology, with central lesions of 29.6% and peripheral diseases of 22.2%. The most common diseases in DBN patients were cerebellar lesions (13.0%, n = 7) and vestibular migraine (13.0%, n = 7), followed by benign positional paroxysmal vertigo (7.4%, n = 4) and drug-related dizziness/vertigo (5.6%, n = 3). The other 48.1% of the patients had unknown etiology. 53.8% (14/26) of patients with idiopathic DBN had decreased semicircular canal function, with 42.9% (6/14) decreased posterior semicircular canal function. The posterior semicircular canal gain in DBN patients decreased compared to the anterior semicircular canal in the same conjugate plane. Patients with peripheral DBN were more prone to horizontal/torsional nystagmus during positional testing. Conclusion: In our study, DBN patients have a relative decrease in posterior semicircular canal gain, which is possibly a particular result found in a subset of downbeat nystagmus patients. The changes in nystagmus during positional testing may be helpful in distinguishing between peripheral and central causes. [ABSTRACT FROM AUTHOR]

Downbeat nystagmus (DBN) is a neuro-otological finding frequently encountered by clinicians dealing with patients with vertigo. Since DBN is a finding that should be understood because of central vestibular dysfunction, it is necessary to know how to frame it promptly to suggest the correct diagnostic-therapeutic pathway to the patient. As knowledge of its pathophysiology has progressed, the importance of this clinical sign has been increasingly understood. At the same time, clinical diagnostic knowledge has increased, and it has been recognized that this sign may occur sporadically or in association with others within defined clinical syndromes. Thus, in many cases, different therapeutic solutions have become possible. In our work, we have attempted to systematize current knowledge about the origin of this finding, the clinical presentation and current treatment options, to provide an overview that can be used at different levels, from the general practitioner to the specialist neurologist or neurotologist.

Summary: Background: GAA-FGF14 disease/spinocerebellar ataxia 27B is a recently described neurodegenerative disease caused by (GAA)≥250 expansions in the fibroblast growth factor 14 (FGF14) gene, but its phenotypic spectrum, pathogenic threshold, and evidence-based treatability remain to be established. We report on the frequency of FGF14 (GAA)≥250 and (GAA)200-249 expansions in a large cohort of patients with idiopathic downbeat nystagmus (DBN) and their response to 4-aminopyridine. Methods: Retrospective cohort study of 170 patients with idiopathic DBN, comprising in-depth phenotyping and assessment of 4-aminopyridine treatment response, including re-analysis of placebo-controlled video-oculography treatment response data from a previous randomised double-blind 4-aminopyridine trial. Findings: Frequency of FGF14 (GAA)≥250 expansions was 48% (82/170) in patients with idiopathic DBN. Additional cerebellar ocular motor signs were observed in 100% (82/82) and cerebellar ataxia in 43% (35/82) of patients carrying an FGF14 (GAA)≥250 expansion. FGF14 (GAA)200-249 alleles were enriched in patients with DBN (12%; 20/170) compared to controls (0.87%; 19/2191; OR, 15.20; 95% CI, 7.52–30.80; p

Abstract Background Low-grade gangliogliomas (GGs) are typically epileptogenic intracranial neoplasms. Yet, the presentation of simplex vertiginous experience and spontaneous downbeat nystagmus (DBN) has not been reported to date. Case presentation We present the case of a 26-year-old male with focal onset impaired awareness seizures, characterized by vertigo due to right temporal lobe epilepsy caused by ganglioglioma. As rare presentations, a spontaneous, consistent DBN in the absence of vertiginous experience was noticed. MRI suggested lesion in the right temporal pole. Twenty-four-hour continuous electroencephalogram (EEG) monitoring recorded periodic sharp and slow waves, originating from the right temporal lobe. The patient was completely relieved of the symptoms after surgical removal of the tumor, which was histologically confirmed as Grade I Ganglioglioma. Conclusions Asides from the cortical pathogenesis of epileptic vertigo, this case also provides insight into the DBN secondary to tumor of the temporal lobe. Moreover, the 24-h EEG is advantageous to recognize vestibular seizures and localize the ictal onset areas.

Objective: We aimed to relate clinical measures of disability in chronic cerebellar degeneration to structural whole-brain changes using voxel-based and surface-based morphometry (vbm and sbm). We were particularly interested in remote effects of cerebellar degeneration in the cerebral cortex. Methods: We recruited 30 patients with cerebellar degeneration of different aetiologies (downbeat nystagmus syndrome, DBN n = 14, spinocerebellar ataxia, SCA n = 9, sporadic adult late-onset ataxia, SAOA n = 7). All patients were thoroughly characterised in the motor, cognitive, vestibular and ocular–motor domains. Vbm and sbm were used to evaluate structural differences between cerebellar degeneration patients and a group of healthy age- and gender-matched volunteers. Linear regression models were used to correlate functional measures of disease progression and postural stability with whole brain volumetry. Results: Patients with SCA and SAOA showed widespread volume loss in the cerebellar hemispheres and less prominently in the vermis. Patients with DBN showed a distinct pattern of grey matter volume (GMV) loss that was restricted to the vestibular and ocular–motor representations in lobules IX, X and V–VII. Falls were associated with brainstem white matter volume. VBM and SBM linear regression models revealed associations between severity of ataxic symptoms, cognitive performance and preferred gait velocity. This included extra-cerebellar (sub-)cortical hubs of the motor and locomotion network (putamen, caudate, thalamus, primary motor cortex, prefrontal cortex) and multisensory areas involved in spatial navigation and cognition. Conclusion: Functional disability in multiple domains was associated with structural changes in the cerebral cortex. [ABSTRACT FROM AUTHOR]

Listeria monocytogenes has tropism towards two immunologically "privileged" sites, the fetoplacental unit in pregnant women and the central nervous system (neurolisteriosis) in immunocompromised individuals. We report a case of neurolisteriosis in a previously asymptomatic pregnant woman from rural West Bengal, India, who presented with a subacute onset febrile illness with features of rhombencephalitis and a predominantly midline-cerebellopathy (slow and dysmetric saccades, florid downbeat nystagmus, horizontal nystagmus, and ataxia). With timely detection and the institution of prolonged intravenous antibiotic therapy, both the mother and the fetus were saved uneventfully. [ABSTRACT FROM AUTHOR]

Background: Low-grade gangliogliomas (GGs) are typically epileptogenic intracranial neoplasms. Yet, the presentation of simplex vertiginous experience and spontaneous downbeat nystagmus (DBN) has not been reported to date. Case presentation: We present the case of a 26-year-old male with focal onset impaired awareness seizures, characterized by vertigo due to right temporal lobe epilepsy caused by ganglioglioma. As rare presentations, a spontaneous, consistent DBN in the absence of vertiginous experience was noticed. MRI suggested lesion in the right temporal pole. Twenty-four-hour continuous electroencephalogram (EEG) monitoring recorded periodic sharp and slow waves, originating from the right temporal lobe. The patient was completely relieved of the symptoms after surgical removal of the tumor, which was histologically confirmed as Grade I Ganglioglioma. Conclusions: Asides from the cortical pathogenesis of epileptic vertigo, this case also provides insight into the DBN secondary to tumor of the temporal lobe. Moreover, the 24-h EEG is advantageous to recognize vestibular seizures and localize the ictal onset areas. [ABSTRACT FROM AUTHOR]

Abstract Introduction Subacute cerebellar ataxia combined with cerebrospinal fluid (CSF) pleocytosis is the result of an immune response that can occur due to viral infections, paraneoplastic diseases or autoimmune-mediated mechanisms. In the following we present the first description of a patient with anti-Homer-3 antibodies in serum and CSF who has been diagnosed with paraneoplastic subacute cerebellar degeneration due to a papillary adenocarcinoma of the breast. Case presentation A 58-year-old female was admitted to our clinical department because of increasing gait and visual disturbances starting nine months ago. The neurological examination revealed a downbeat nystagmus, oscillopsia, a severe standing and gait ataxia and a slight dysarthria. Cranial MRI showed no pathological findings. Examination of CSF showed a lymphocytic pleocytosis of 11 cells/µl and an intrathecal IgG synthesis of 26%. Initially, standard serological testing in serum and CSF did not indicate any autoimmune or paraneoplastic aetiology. However, an antigen-specific indirect immunofluorescence test (IIFT) revealed the presence of anti-Homer-3 antibodies (IgG) with a serum titer of 1: 32,000 and a titer of 1: 100 in CSF. Subsequent histological examination of a right axillary lymph node mass showed papillary adenocarcinoma cells. Breast MRI detected multiple bilateral lesions as a diffuse tumour manifestation indicative of adenocarcinoma of the breast. Treatment with high-dose methylprednisolone followed by five plasmaphereses and treatment with 4-aminopyridine resulted in a moderate decrease of the downbeat nystagmus and she was able to move independently with a wheeled walker after 3 weeks. The patient was subsequently treated with chemotherapy (epirubicin, cyclophosphamide) and two series of immunoglobulins (5 × 30 g each). This resulted in a moderate improvement of the cerebellar symptoms with a decrease of ataxia and disappearance of the downbeat nystagmus. Conclusion The presented case of anti-Homer-3 antibody-associated cerebellar degeneration is the first that is clearly associated with the detection of a tumour. Interestingly, the Homer-3 protein interaction partner metabotropic glutamate receptor subtype 1A (mGluR1A) is predominantly expressed in Purkinje cells where its function is essential for motor coordination and motor learning. Based on our findings, in subacute cerebellar degeneration, we recommend considering serological testing for anti-Homer-3 antibodies in serum and cerebrospinal fluid together with tumor screening.

Aims of the present article are: 1) assessing vestibular contribution to spatial navigation, 2) exploring how age, global positioning systems (GPS) use, and vestibular navigation contribute to subjective sense of direction (SOD), 3) evaluating vestibular navigation in patients with lesions of the vestibular-cerebellum (patients with downbeat nystagmus, DBN) that could inform on the signals carried by vestibulo-cerebellar-cortical pathways. We applied two navigation tasks on a rotating chair in the dark: return-to-start (RTS), where subjects drive the chair back to the origin after discrete angular displacement stimuli (path reversal), and complete-the-circle (CTC) where subjects drive the chair on, all the way round to origin (path completion). We examined 24 normal controls (20-83 yr), five patients with DBN (62-77 yr) and, as proof of principle, two patients with early dementia (84 and 76 yr). We found a relationship between SOD, assessed by Santa Barbara Sense of Direction Scale, and subject's age (positive), GPS use (negative), and CTC-vestibular-navigation-task (positive). Age-related decline in vestibular navigation was observed with the RTS task but not with the complex CTC task. Vestibular navigation was normal in patients with vestibulo-cerebellar dysfunction but abnormal, particularly CTC, in the demented patients. We conclude that vestibular navigation skills contribute to the build-up of our SOD. Unexpectedly, perceived SOD in the elderly is not inferior, possibly explained by increased GPS use by the young. Preserved vestibular navigation in cerebellar patients suggests that ascending vestibular-cerebellar projections carry velocity (not position) signals. The abnormalities in the cognitively impaired patients suggest that their vestibulo-spatial navigation is disrupted. [ABSTRACT FROM AUTHOR]

Downbeat nystagmus (DBN) is a common form of acquired fixation nystagmus related to vestibulo-cerebellar impairments and associated with impaired vision and postural imbalance. DBN intensity becomes modulated by various factors such as gaze direction, head position, daytime, and resting conditions. Further evidence suggests that locomotion attenuates postural symptoms in DBN. Here, we examined whether walking might analogously influence ocular-motor deficits in DBN. Gaze stabilization mechanisms and nystagmus frequency were examined in 10 patients with DBN and 10 age-matched healthy controls with visual fixation during standing vs. walking on a motorized treadmill. Despite their central ocular-motor deficits, linear and angular gaze stabilization in the vertical plane were functional during walking in DBN patients and comparable to controls. Notably, nystagmus frequency in patients was considerably reduced during walking compared to standing (p < 0.001). The frequency of remaining nystagmus during walking was further modulated in a manner that depended on the specific phase of the gait cycle (p = 0.015). These attenuating effects on nystagmus intensity during walking suggest that ocular-motor control disturbances are selectively suppressed during locomotion in DBN. This suppression is potentially mediated by locomotor efference copies that have been shown to selectively govern gaze stabilization during stereotyped locomotion in animal models. [ABSTRACT FROM AUTHOR]

Introduction: Subacute cerebellar ataxia combined with cerebrospinal fluid (CSF) pleocytosis is the result of an immune response that can occur due to viral infections, paraneoplastic diseases or autoimmune-mediated mechanisms. In the following we present the first description of a patient with anti-Homer-3 antibodies in serum and CSF who has been diagnosed with paraneoplastic subacute cerebellar degeneration due to a papillary adenocarcinoma of the breast. Case presentation: A 58-year-old female was admitted to our clinical department because of increasing gait and visual disturbances starting nine months ago. The neurological examination revealed a downbeat nystagmus, oscillopsia, a severe standing and gait ataxia and a slight dysarthria. Cranial MRI showed no pathological findings. Examination of CSF showed a lymphocytic pleocytosis of 11 cells/µl and an intrathecal IgG synthesis of 26%. Initially, standard serological testing in serum and CSF did not indicate any autoimmune or paraneoplastic aetiology. However, an antigen-specific indirect immunofluorescence test (IIFT) revealed the presence of anti-Homer-3 antibodies (IgG) with a serum titer of 1: 32,000 and a titer of 1: 100 in CSF. Subsequent histological examination of a right axillary lymph node mass showed papillary adenocarcinoma cells. Breast MRI detected multiple bilateral lesions as a diffuse tumour manifestation indicative of adenocarcinoma of the breast. Treatment with high-dose methylprednisolone followed by five plasmaphereses and treatment with 4-aminopyridine resulted in a moderate decrease of the downbeat nystagmus and she was able to move independently with a wheeled walker after 3 weeks. The patient was subsequently treated with chemotherapy (epirubicin, cyclophosphamide) and two series of immunoglobulins (5 × 30 g each). This resulted in a moderate improvement of the cerebellar symptoms with a decrease of ataxia and disappearance of the downbeat nystagmus. Conclusion: The presented case of anti-Homer-3 antibody-associated cerebellar degeneration is the first that is clearly associated with the detection of a tumour. Interestingly, the Homer-3 protein interaction partner metabotropic glutamate receptor subtype 1A (mGluR1A) is predominantly expressed in Purkinje cells where its function is essential for motor coordination and motor learning. Based on our findings, in subacute cerebellar degeneration, we recommend considering serological testing for anti-Homer-3 antibodies in serum and cerebrospinal fluid together with tumor screening. [ABSTRACT FROM AUTHOR]

Background: Atypical posterior canal (PC) positional nystagmus may be due to the changes in cupular response dynamics from cupulolithiasis (cu), canalithiasis of the short arm (ca-sa), or a partial/complete obstruction-jam. Factors that change the dynamics are the position of the head in the pitch plane, individual variability in the location of the PC attachment to the utricle and the position of the cupula within the ampulla, and the location of debris within the short arm and on the cupula. The clinical presentation of PC-BPPV-cu is DBN with torsion towards the contralateral side in the DH positions and SHHP or no nystagmus in the ipsilateral DH position and no nystagmus upon return to sitting from each position. The clinical presentation of PC-BPPV-ca-sa is no nystagmus in the DH position and upbeat nystagmus (UBN) with torsion lateralized to the involved side upon return to sitting from each position. Case description: A 68-year-old woman, diagnosed with BPPV, presented with DBN associated with vertigo in both DH positions and without nystagmus or symptoms on sitting up. In the straight head hanging position (SHHP), the findings of a transient burst of UBN with left torsion associated with vertigo suggested ipsicanal conversion from the left PC-BPPV-cu to canalithiasis. Treatment included a modified canalith repositioning procedure (CRP), which resulted in complete resolution. BPPV recurred 17 days later. Clinical presentation of BPPV included no nystagmus/symptoms in both the contralateral DH position and SHHP, DBN in the ipsilateral DH position without symptoms, and UBN with left torsion associated with severe truncal retropulsion and nausea on sitting up from provoking position. The findings suggested the left PC-BPPV-cu-sa and PC-BPPV-ca-sa. Treatment included neck extension, a modified CRP, and demi-Semont before complete resolution. Conclusion: An understanding of the biomechanics of the vestibular system is necessary to differentially diagnose atypical PC-BPPV. DH test (DHT) findings suggest that PC-BPPV-cu presents with DBN or no nystagmus in one or two DH positions and sometimes SHHP and without nystagmus or no reversal/reversal of nystagmus on sitting up. The findings suggest PC-BPPV-ca-sa has no nystagmus in DH positions or DBN in the ipsilateral DH position and UBN with torsion lateralized to the involved side on sitting up. [ABSTRACT FROM AUTHOR]

Neuromyelitis optica (NMO), an autoimmune disease, typically presents with loss of vision and myelopathic signs. NMO may be associated with antibodies selective for aquaporin-4 (AQP4), a water channel located within the optic nerves and spinal cord.AQP4 is distributed in the periventricular region, corpus callosum, magnocellular nuclei of the hypothalamus, and brain stem.Downbeat nystagmus (DBN) is associated with structural, metabolic, and autoimmune disorders, but is rarely reported in NMO.We treated a 33-year-old female with known AQP4-positive NMO who presented with new-onset DBN. We review the literature and discuss possible mechanisms and lesion locations hypothetically responsible for the symptoms and signs., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Canut et al.)

BackgroundAtypical posterior canal (PC) positional nystagmus may be due to the changes in cupular response dynamics from cupulolithiasis (cu), canalithiasis of the short arm (ca-sa), or a partial/complete obstruction—jam. Factors that change the dynamics are the position of the head in the pitch plane, individual variability in the location of the PC attachment to the utricle and the position of the cupula within the ampulla, and the location of debris within the short arm and on the cupula. The clinical presentation of PC-BPPV-cu is DBN with torsion towards the contralateral side in the DH positions and SHHP or no nystagmus in the ipsilateral DH position and no nystagmus upon return to sitting from each position. The clinical presentation of PC-BPPV-ca-sa is no nystagmus in the DH position and upbeat nystagmus (UBN) with torsion lateralized to the involved side upon return to sitting from each position.Case descriptionA 68-year-old woman, diagnosed with BPPV, presented with DBN associated with vertigo in both DH positions and without nystagmus or symptoms on sitting up. In the straight head hanging position (SHHP), the findings of a transient burst of UBN with left torsion associated with vertigo suggested ipsicanal conversion from the left PC-BPPV-cu to canalithiasis. Treatment included a modified canalith repositioning procedure (CRP), which resulted in complete resolution. BPPV recurred 17 days later. Clinical presentation of BPPV included no nystagmus/symptoms in both the contralateral DH position and SHHP, DBN in the ipsilateral DH position without symptoms, and UBN with left torsion associated with severe truncal retropulsion and nausea on sitting up from provoking position. The findings suggested the left PC-BPPV-cu-sa and PC-BPPV-ca-sa. Treatment included neck extension, a modified CRP, and demi-Semont before complete resolution.ConclusionAn understanding of the biomechanics of the vestibular system is necessary to differentially diagnose atypical PC-BPPV. DH test (DHT) findings suggest that PC-BPPV-cu presents with DBN or no nystagmus in one or two DH positions and sometimes SHHP and without nystagmus or no reversal/reversal of nystagmus on sitting up. The findings suggest PC-BPPV-ca-sa has no nystagmus in DH positions or DBN in the ipsilateral DH position and UBN with torsion lateralized to the involved side on sitting up.

Downbeat nystagmus (DBN) observed in head-hanging positions, may be of central or peripheral origin. Central DBN in head-hanging positions is mostly due to a disorder of the vestibulo-cerebellum, whereas peripheral DBN is usually attributed to canalolithiasis of an anterior semicircular canal. Here, we describe an atypical case of a patient who, after head trauma, experienced severe and stereotypic vertigo attacks after being placed in various head-hanging positions. Vertigo lasted 10–15 s and was always associated with a robust DBN. The provocation of transient vertigo and DBN, which both showed no decrease upon repetition of maneuvers, depended on the yaw orientation relative to the trunk and the angle of backward pitch. On a motorized, multi-axis turntable, we identified the two-dimensional Helmholtz coordinates of head positions at which vertigo and DBN occurred (y-axis: horizontal, space-fixed; z-axis: vertical, and head-fixed; x-axis: torsional, head-fixed, and unchanged). This two-dimensional area of DBN-associated head positions did not change when whole-body rotations took different paths (e.g., by forwarding pitch) or were executed with different velocities. Moreover, the intensity of DBN was also independent of whole-body rotation paths and velocities. So far, therapeutic approaches with repeated liberation maneuvers and cranial vibrations were not successful. We speculate that vertigo and DBN in this patient are due to macular damage, possibly an unstable otolithic membrane that, in specific orientations relative to gravity, slips into a position causing paroxysmal stimulation or inhibition of macular hair cells.

Kestenbaum-Anderson–like operations have proven beneficial in treatment of compensatory head tilt in patients with infantile nystagmus. However, their use in acquired vertical nystagmus in adults with head tilt has rarely been reported. Presented here is a case of a 52-year-old woman with acquired downbeat nystagmus with a significant head tilt who responded to a simple two-muscle surgery involving the superior recti. Cyclovertical muscle surgery should be considered a viable option in such patients who are refractory to medical intervention. Additionally, it appears that four-muscle vertical muscle recessions (two muscles per eye) may not be necessary to dampen vertical nystagmus since good results can be obtained with a single muscle recession bilaterally. [ABSTRACT FROM AUTHOR]

This case study describes transient downbeat nystagmus with vertigo due to a bilateral Bow Hunters Syndrome that was initially treated for 7 months as a peripheral benign paroxysmal positional vertigo. Normal static angiography and imaging studies (magnetic resonance, computed tomography) contributed to the mis-diagnosis. However, not until positional testing with the patient in upright (non-gravity dependent) was a transient downbeat nystagmus revealed with vertigo. The patient was referred for neurosurgical consult. Unfortunately, surgery was delayed due to suicidal ideation and hospitalization. Eventually, vertigo symptoms resolved following a C4-5 anterior cervical dissection and fusion. This case highlights the critical inclusion of non-gravity dependent position testing as an augment to the positional testing component of the clinical examination as well as the extreme duress that prolonged positional vertigo can cause. [ABSTRACT FROM AUTHOR]

Hyperventilation-induced downbeat nystagmus (HV-DBN) has been reported in cerebellar disorders and explained by a loss of the inhibitory cerebellar output via a metabolic effect on cerebellar Ca2+ channels. The aim of this study was to determine the clinical characteristics and underlying pathogenesis of episodic vestibular syndrome (EVS) with HV-DBN. Of 667 patients with EVS, we recruited 22 with HV-DBN and assessed their clinical characteristics, video-oculographic findings, and the results of molecular genetic analyses. The age at symptom onset was 47.5 ± 13.0 years (mean ± SD), and there was a female preponderance (n = 15, 68%). The duration of vertigo/dizziness attacks ranged from minutes to a few days, and 11 patients (50%) fulfilled the diagnostic criteria for vestibular migraine. HV-induced new-onset DBN in 8 patients, while the remaining 14 showed augmentation of spontaneous DBN by HV. The maximum slow-phase velocity of HV-DBN ranged from 2.2 to 11.9°/s, which showed a statistical difference with that of spontaneous DBN (median = 4.95, IQR = 3.68–6.55 vs. median = 1.25, IQR = 0.20–2.15, p < 0.001). HV-DBN was either purely downbeat (n = 11) or accompanied with small horizontal components (n = 11). Other neuro-otologic findings included perverted head-shaking nystagmus (n = 11), central positional nystagmus (n = 7), saccadic pursuit (n = 3), and horizontal gaze-evoked nystagmus (n = 1). Gene expression profiling with a bioinformatics analysis identified 43 upregulated and 49 downregulated differentially expressed genes (DEGs) in patients with EVS and HV-DBN and revealed that the downregulated DEGs were significantly enriched in terms related to the ribosome pathway. Our results suggest that the underlying cerebellar dysfunction would be responsible for paroxysmal attacks of vertigo in patients with EVS and HV-DBN. [ABSTRACT FROM AUTHOR]

This case study describes transient downbeat nystagmus with vertigo due to a bilateral Bow Hunters Syndrome that was initially treated for 7 months as a peripheral benign paroxysmal positional vertigo. Normal static angiography and imaging studies (magnetic resonance, computed tomography) contributed to the mis-diagnosis. However, not until positional testing with the patient in upright (non-gravity dependent) was a transient downbeat nystagmus revealed with vertigo. The patient was referred for neurosurgical consult. Unfortunately, surgery was delayed due to suicidal ideation and hospitalization. Eventually, vertigo symptoms resolved following a C4-5 anterior cervical dissection and fusion. This case highlights the critical inclusion of non-gravity dependent position testing as an augment to the positional testing component of the clinical examination as well as the extreme duress that prolonged positional vertigo can cause.

Background: Meniere's disease is often characterized by a changing horizontal nystagmus during the crisis; however, vertical nystagmus is not often detected. The horizontal nystagmus is frequently studied in the irritative or destructive phases of the disease. Clinical findings: We report the case of a 70 years-old man suffering for 3 years of Meniere's disease in his right ear. During an attack we found an infrequent nystagmus that was a downbeat nystagmus in primary position. He was then closely followed in the ward during 5 days and daily tests were performed. We first ruled out a central cause and were able to explain that as due to a peripheral deficit in the right posterior semicircular canal. Other features of the vertigo attacks in patients with MD were recorded. Summary: We studied a patient presenting a vertigo attack with a downbeat nystagmus. Our findings show that this nystagmus was caused by his own Meniere's disease, specifically by a posterior canal hypofunction, and not by a central disorder. There is no evidence about this kind of nystagmus in Meniere disease and, to the best to our knowledge, this is one of the first reports its evaluation using the test nowadays available. Conclusion: In this case, our result demonstrate that the downbeat nystagmus was caused by a hypofunction of the posterior semicircular canal.

Purpose: To test the hypothesis that eye muscle surgery in treatment of patients with acquired downbeat nystagmus results in improvement measures of visual and ocular motor function. Methods: This is a prospective, interventional case series analysis of clinical and electrophyisological data before and after eye muscle surgery in 17 patients with acquired downbeat nystagmus who did not respond to medical treatments. Outcome measures included: 1) routine demography and clinical characteristics, 2) subjective oscillopsia (SO), 3) binocular best-corrected visual acuity in the null position (BVA), 3) primary position strabismic deviation (SD), 5) anomalous head posture (AHP), 6) contrast sensitivity function (CS), and 7) nystagmus slow phase velocity (SPV). All patients were followed at least 12 months. Parametric and non-parametric statistical analysis of outcome measure data above pre- and post-treatment were perfomed using standard software on grouped data using computerized software. Results: Patients' age ranged from 5 to 85 years (average 27 years). About 59% were male. Follow up ranged from 1–10 years (average 2.0 years). Around 70% had an associated central nervous systemic diagnosis, 100% had an AHP, oscillopsia and decreased CS, 53% had other eye disease, and 59% had strabismus. There were no complications from surgery. There were signficant post-treatment improvements in mean/median group BVA, SO, SD, AHP, CS, and SPV. Conclusion: This study supports the hypothesis that eye muscle surgery as treatments for patients with acquired downbeat nystagmus can result in improvements in multiple aspects of ocular motor and visual functions.

Downbeat nystagmus (DBN) observed in head-hanging positions, may be of central or peripheral origin. Central DBN in head-hanging positions is mostly due to a disorder of the vestibulo-cerebellum, whereas peripheral DBN is usually attributed to canalolithiasis of an anterior semicircular canal. Here, we describe an atypical case of a patient who, after head trauma, experienced severe and stereotypic vertigo attacks after being placed in various head-hanging positions. Vertigo lasted 10–15 s and was always associated with a robust DBN. The provocation of transient vertigo and DBN, which both showed no decrease upon repetition of maneuvers, depended on the yaw orientation relative to the trunk and the angle of backward pitch. On a motorized, multi-axis turntable, we identified the two-dimensional Helmholtz coordinates of head positions at which vertigo and DBN occurred (y-axis: horizontal, space-fixed; z-axis: vertical, and head-fixed; x-axis: torsional, head-fixed, and unchanged). This two-dimensional area of DBN-associated head positions did not change when whole-body rotations took different paths (e.g., by forwarding pitch) or were executed with different velocities. Moreover, the intensity of DBN was also independent of whole-body rotation paths and velocities. So far, therapeutic approaches with repeated liberation maneuvers and cranial vibrations were not successful. We speculate that vertigo and DBN in this patient are due to macular damage, possibly an unstable otolithic membrane that, in specific orientations relative to gravity, slips into a position causing paroxysmal stimulation or inhibition of macular hair cells. [ABSTRACT FROM AUTHOR]

Background: GAA-FGF14 disease/spinocerebellar ataxia 27B is a recently described neurodegenerative disease caused by (GAA) ≥250 expansions in the fibroblast growth factor 14 (FGF14) gene, but its phenotypic spectrum, pathogenic threshold, and evidence-based treatability remain to be established. We report on the frequency of FGF14 (GAA) ≥250 and (GAA) 200-249 expansions in a large cohort of patients with idiopathic downbeat nystagmus (DBN) and their response to 4-aminopyridine., Methods: Retrospective cohort study of 170 patients with idiopathic DBN, comprising in-depth phenotyping and assessment of 4-aminopyridine treatment response, including re-analysis of placebo-controlled video-oculography treatment response data from a previous randomised double-blind 4-aminopyridine trial., Findings: Frequency of FGF14 (GAA) ≥250 expansions was 48% (82/170) in patients with idiopathic DBN. Additional cerebellar ocular motor signs were observed in 100% (82/82) and cerebellar ataxia in 43% (35/82) of patients carrying an FGF14 (GAA) ≥250 expansion. FGF14 (GAA) 200-249 alleles were enriched in patients with DBN (12%; 20/170) compared to controls (0.87%; 19/2191; OR, 15.20; 95% CI, 7.52-30.80; p < 0.0001). The phenotype of patients carrying a (GAA) 200-249 allele closely mirrored that of patients carrying a (GAA) ≥250 allele. Patients carrying a (GAA) ≥250 or a (GAA) 200-249 allele had a significantly greater clinician-reported (80%, 33/41 vs 31%, 5/16; RR, 2.58; 95% CI, 1.23-5.41; Fisher's exact test, p = 0.0011) and self-reported (59%, 32/54 vs 11%, 2/19; RR, 5.63; 95% CI, 1.49-21.27; Fisher's exact test, p = 0.00033) response to 4-aminopyridine treatment compared to patients carrying a (GAA) <200 allele. Placebo-controlled video-oculography data, available for four patients carrying an FGF14 (GAA) ≥250 expansion, showed a significant decrease in slow phase velocity of DBN with 4-aminopyridine, but not placebo., Interpretation: This study confirms that FGF14 GAA expansions are a frequent cause of DBN syndromes. It provides preliminary evidence that (GAA) 200-249 alleles might be pathogenic. Finally, it provides large real-world and preliminary piloting placebo-controlled evidence for the efficacy of 4-aminopyridine in GAA-FGF14 disease., Funding: This work was supported by the Clinician Scientist program "PRECISE.net" funded by the Else Kröner-Fresenius-Stiftung (to CW, AT, and MSy), the grant 779257 "Solve-RD" from the European's Union Horizon 2020 research and innovation program (to MSy), and the grant 01EO 1401 by the German Federal Ministry of Education and Research (BMBF) (to MSt). This work was also supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) N° 441409627, as part of the PROSPAX consortium under the frame of EJP RD, the European Joint Programme on Rare Diseases, under the EJP RD COFUND-EJP N° 825575 (to MSy, BB and-as associated partner-SZ), the NIH National Institute of Neurological Disorders and Stroke (grant 2R01NS072248-11A1 to SZ), the Fondation Groupe Monaco (to BB), and the Montreal General Hospital Foundation (grant PT79418 to BB). The Care4Rare Canada Consortium is funded in part by Genome Canada and the Ontario Genomics Institute (OGI-147 to KMB), the Canadian Institutes of Health Research (CIHR GP1-155867 to KMB), Ontario Research Foundation, Genome Quebec, and the Children's Hospital of Eastern Ontario Foundation. The funders had no role in the conduct of this study., Competing Interests: Declaration of interests DP, FH, CW, MCD, AT, CA, MJD, AC, GDG, KMB, JC, AMH, and BB report no disclosures. DR has received grant/research support from Janssen and Lundbeck; he has served as a consultant or on advisory boards for AC Immune, Janssen, Roche and Rovi and he has served on speakers bureaus of Janssen and Pharmagenetix. He also received honoraria from Gerot Lannacher, Janssen and Pharmagenetix, and travel support from Angelini and Janssen, all unrelated to the present manuscript. SZ has received consultancy honoraria from Neurogene, Aeglea BioTherapeutics, Applied Therapeutics, and is an unpaid officer of the TGP foundation, all unrelated to the present manuscript. MSt is Joint Chief Editor of the Journal of Neurology, Editor in Chief of Frontiers of Neuro-otology and Section Editor of F1000. He has received speakers honoraria from Abbott, Auris Medical, Biogen, Eisai, Grünenthal, GSK, Henning Pharma, Interacoustics, J&J, MSD, NeuroUpdate, Otometrics, Pierre-Fabre, TEVA, UCB, and Viatris. He receives support for clinical studies from Decibel, U.S.A., Cure within Reach, U.S.A. and Heel, Germany. He distributes M-glasses and Positional vertigo App. He acts as a consultant for Abbott, AurisMedical, Bulbitec, Heel, IntraBio, Sensorion and Vertify. He is an investor and share-holder of IntraBio. All are unrelated to the present manuscript. MSy has received consultancy honoraria from Janssen, Ionis, Orphazyme, Servier, Reata, Biohaven, Zevra, Lilly, GenOrph, and AviadoBio, all unrelated to the present manuscript. MSy is planning a treatment trial of 4-AP in GAA-FGF14 disease together with Solaxa Inc. as a sponsor, but has not received any type of honoraria or funding from Solaxa., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: To elucidate the mechanism of paroxysmal central positional nystagmus (CPN) by determining the effects of head rotation velocity on the intensity of paroxysmal downbeat nystagmus induced during straight head hanging (SHH).Methods: We recruited 21 patients with paroxysmal downbeat CPN induced during SHH at the Dizziness Center of Seoul National University Bundang Hospital from September 2018 to July 2019. Twenty-one patients had manual SHH at two different lying velocities, the fast (routine) and slow, and they also underwent SHH at different rotation velocities of 10, 20, 30, and 40 °/s using a motorized rotation chair. Induced nystagmus was recorded using video-oculography and the maximum slow phase velocity (SPV) and time constant (TC) of the induced paroxysmal nystagmus were analyzed.Results: During manual SHH, paroxysmal downbeat nystagmus was invariably induced during routine SHH (fast lying down), but absent or minimal during slow positioning. During motorized SHH, the median of maximum intensity of downbeat nystagmus increased from 7.6 °/s (0–16.9) to 14.0 °/s (0–32.5), 16.5 °/s (0–44.6), and 19.1 °/s (0–55.2) as the rotation velocity increased from 10 to 20, 30, and 40°/s (P < 0.001, P < 0.001, P = 0.004; linear mixed models). In contrast, the TCs of paroxysmal downbeat CPN remained unchanged (P = 0.558, P = 0.881, P = 0.384, linear mixed models).Conclusions: The dependence of nystagmus intensity on head rotation velocity supports a disinhibited and exaggerated inhibitory rebound of the canal signals as the mechanism of paroxysmal CPN.

Positional downbeat nystagmus (pDBN) represents a relatively frequent finding. Its possible peripheral origin has been widely ascertained. Nevertheless, distinguishing features of peripheral positional nystagmus, including latency, paroxysm and torsional components, may be missing, resulting in challenging differential diagnosis with central pDBN. Moreover, in case of benign paroxysmal positional vertigo (BPPV), detection of the affected canal may be challenging as involvement of the non-ampullary arm of posterior semicircular canal (PSC) results in the same oculomotor responses generated by contralateral anterior canal (ASC)-canalolithiasis. Recent acquisitions suggest that patients with persistent pDBN due to vertical canal-BPPV may exhibit impaired vestibulo-ocular reflex (VOR) for the involved canal on video-head impulse test (vHIT). Since canal hypofunction normalizes following proper canalith repositioning procedures (CRP), an incomplete canalith jam acting as a “low-pass filter” for the affected ampullary receptor has been hypothesized. This study aims to determine the sensitivity of vHIT in detecting canal involvement in patients presenting with pDBN due to vertical canal-BPPV. We retrospectively reviewed the clinical records of 59 consecutive subjects presenting with peripheral pDBN. All patients were tested with video-Frenzel examination and vHIT at presentation and after resolution of symptoms or transformation in typical BPPV-variant. BPPV involving non-ampullary tract of PSC was diagnosed in 78%, ASC-BPPV in 11.9% whereas in 6 cases the involved canal remained unidentified. Presenting VOR-gain values for the affected canal were greatly impaired in cases with persistent pDBN compared to subjects with paroxysmal/transitory nystagmus (p < 0.001). Each patient received CRP for BPPV involving the hypoactive canal or, in case of normal VOR-gain, the assumed affected canal. Each subject exhibiting VOR-gain reduction for the involved canal developed normalization of vHIT data after proper repositioning (p < 0.001), proving a close relationship with otoliths altering high-frequency cupular responses. According to our results, overall vHIT sensitivity in detecting the affected SC was 72.9%, increasing up to 88.6% when considering only cases with persistent pDBN where an incomplete canal plug is more likely to occur. vHIT should be routinely used in patients with pDBN as it may enable to localize otoconia within the labyrinth, providing further insights to the pathophysiology of peripheral pDBN.

Isolated brain stem tuberculoma constitutes about 5% of all intracranial tuberculomas. A case of isolated inferior rectus palsy with downbeat nystagmus due to presumed midbrain tuberculoma in an immunocompetent patient is described here. This report documents a rare entity of a combination of partial third nerve palsy with pupil involvement along with downbeat nystagmus.

Objectives: To elucidate the mechanism of paroxysmal central positional nystagmus (CPN) by determining the effects of head rotation velocity on the intensity of paroxysmal downbeat nystagmus induced during straight head hanging (SHH). Methods: We recruited 21 patients with paroxysmal downbeat CPN induced during SHH at the Dizziness Center of Seoul National University Bundang Hospital from September 2018 to July 2019. Twenty-one patients had manual SHH at two different lying velocities, the fast (routine) and slow, and they also underwent SHH at different rotation velocities of 10, 20, 30, and 40 °/s using a motorized rotation chair. Induced nystagmus was recorded using video-oculography and the maximum slow phase velocity (SPV) and time constant (TC) of the induced paroxysmal nystagmus were analyzed. Results: During manual SHH, paroxysmal downbeat nystagmus was invariably induced during routine SHH (fast lying down), but absent or minimal during slow positioning. During motorized SHH, the median of maximum intensity of downbeat nystagmus increased from 7.6 °/s (0–16.9) to 14.0 °/s (0–32.5), 16.5 °/s (0–44.6), and 19.1 °/s (0–55.2) as the rotation velocity increased from 10 to 20, 30, and 40°/s (P < 0.001, P < 0.001, P = 0.004; linear mixed models). In contrast, the TCs of paroxysmal downbeat CPN remained unchanged (P = 0.558, P = 0.881, P = 0.384, linear mixed models). Conclusions: The dependence of nystagmus intensity on head rotation velocity supports a disinhibited and exaggerated inhibitory rebound of the canal signals as the mechanism of paroxysmal CPN. [ABSTRACT FROM AUTHOR]

Positional downbeat nystagmus (pDBN) represents a relatively frequent finding. Its possible peripheral origin has been widely ascertained. Nevertheless, distinguishing features of peripheral positional nystagmus, including latency, paroxysm and torsional components, may be missing, resulting in challenging differential diagnosis with central pDBN. Moreover, in case of benign paroxysmal positional vertigo (BPPV), detection of the affected canal may be challenging as involvement of the non-ampullary arm of posterior semicircular canal (PSC) results in the same oculomotor responses generated by contralateral anterior canal (ASC)-canalolithiasis. Recent acquisitions suggest that patients with persistent pDBN due to vertical canal-BPPV may exhibit impaired vestibulo-ocular reflex (VOR) for the involved canal on video-head impulse test (vHIT). Since canal hypofunction normalizes following proper canalith repositioning procedures (CRP), an incomplete canalith jam acting as a "low-pass filter" for the affected ampullary receptor has been hypothesized. This study aims to determine the sensitivity of vHIT in detecting canal involvement in patients presenting with pDBN due to vertical canal-BPPV. We retrospectively reviewed the clinical records of 59 consecutive subjects presenting with peripheral pDBN. All patients were tested with video-Frenzel examination and vHIT at presentation and after resolution of symptoms or transformation in typical BPPV-variant. BPPV involving non-ampullary tract of PSC was diagnosed in 78%, ASC-BPPV in 11.9% whereas in 6 cases the involved canal remained unidentified. Presenting VOR-gain values for the affected canal were greatly impaired in cases with persistent pDBN compared to subjects with paroxysmal/transitory nystagmus (p < 0.001). Each patient received CRP for BPPV involving the hypoactive canal or, in case of normal VOR-gain, the assumed affected canal. Each subject exhibiting VOR-gain reduction for the involved canal developed normalization of vHIT data after proper repositioning (p < 0.001), proving a close relationship with otoliths altering high-frequency cupular responses. According to our results, overall vHIT sensitivity in detecting the affected SC was 72.9%, increasing up to 88.6% when considering only cases with persistent pDBN where an incomplete canal plug is more likely to occur. vHIT should be routinely used in patients with pDBN as it may enable to localize otoconia within the labyrinth, providing further insights to the pathophysiology of peripheral pDBN. [ABSTRACT FROM AUTHOR]

Objective: To report clinical and ancillary findings in a kindred with spinocerebellar ataxia 38 (SCA38). Patients and methods: Five family members spanning two generations developed gait ataxia and intermittent diplopia. On examination, a cerebellar syndrome accompanied by downbeat nystagmus and a saccadic head impulse test (HIT) were found. Results: Whole-exome sequencing demonstrated a heterozygous variant in ELOVL5, c.779A > G (p.Tyr260Cys), in four tested patients. Intermittent concomitant esotropia and hypertropia caused transient diplopia in one individual each. Saccadic HIT responses were found in four subjects. Sensorineural hypoacusis was present in every case. Electrophysiological studies demonstrated a sensory neuronopathy in patients from the first generation, with prolonged disease duration. Baseline serum docosahexaenoic acid (DHA) percent was diminished in four individuals. Oral 26-week dietary DHA supplementation, 650 mg/day, raised serum DHA percent and induced a statistically significant reduction in Scale for the Assessment and Rating of Ataxia (SARA) total scores, and in stance and heel–shin slide item scores. Conclusion: The mentioned ELOVL5 variant segregated with disease in this kindred. Downbeat nystagmus, intermittent heterotropia causing transient diplopia, vestibular impairment demonstrated by abnormal HIT, and sensory neuronopathy were part of the clinical picture in this series. DHA supplementation raised serum DHA percent in cases with diminished levels, and induced a clinical amelioration and a statistically significant reduction in SARA scores in the study group. Further studies are needed to investigate the role of these findings in SCA38, and to determine the response to prolonged DHA supplementation. [ABSTRACT FROM AUTHOR]

Upward and downward bias of eye movement signals in the semicircular canals (SCC)- and/or otolith-related central pathways have been proposed to explain the occurrence of vertical nystagmus (downbeat nystagmus [DBN] and upbeat nystagmus [UBN]) and its frequent modulation with head position. Video-head impulse test (VHIT), usually performed in upright position, is a recent development for measuring SCC function. We performed longitudinal nystagmus and VHIT assessments in different head positions in a patient with probable thiamine deficiency, in order to explore a possible relationship between the positional behavior of vertical nystagmus and SCC function. Initially, UBN in upright position changed to DBN in prone position and remained relatively unchanged in supine position. This was associated with both anterior and posterior SCC hyperactive responses in upright position, and a relative enhancement of the anterior SCC responses in prone position and the posterior SCC responses in supine position. Over 1 year, in prone position, change from UBN to DBN and the enhancement of anterior SCC responses remained, while in supine position, UBN either decreased or changed to DBN, when compared to upright position. This was associated with a relative enhancement of the anterior SCC responses in supine position, albeit inconsistently, and the presence of posterior SCC hypoactive responses in all positions, including prone. While not contradicting a primary otolithic dysfunction in the genesis of UBN change to DBN with head position, we provide evidence for positional modulation of SCC function in thiamine deficiency and a possible relationship with nystagmus positional behavior. [ABSTRACT FROM AUTHOR]

Downbeat nystagmus (DBN) is a frequent form of acquired persisting central fixation nystagmus, often associated with other cerebellar ocular signs, such as saccadic smooth pursuit or gaze-holding deficits. Despite its distinct clinical features, the underlying etiology of DBN often remains unclear. Therefore, a genome-wide association study (GWAS) was conducted in 106 patients and 2609 healthy controls of European ancestry to identify genetic variants associated with DBN. A genome-wide significant association (p < 5 × 10−8) with DBN was found for a variation on chromosome 13 located within the fibroblast growth factor 14 gene (FGF14). FGF14 is expressed in Purkinje cells (PCs) and a reduction leads to a decreased spontaneous firing rate and excitability of PCs, compatible with the pathophysiology of DBN. In addition, mutations in the FGF14 gene cause spinocerebellar ataxia type 27. Suggestive associations (p < 1 × 10−05) could be detected for 15 additional LD-independent loci, one of which is also located in the FGF14 gene. An association of a region containing the dihydrofolate reductase (DHFR) and MutS Homolog 3 (MSH3) genes on chromosome 5 was slightly below the genome-wide significance threshold. DHFR is relevant for neuronal regulation, and a dysfunction is known to induce cerebellar damage. Among the remaining twelve suggestive associations, four genes (MAST4, TPPP, FTMT, and IDS) seem to be involved in cerebral pathological processes. Thus, this GWAS analysis has identified a potential genetic contribution to idiopathic DBN, including suggestive associations to several genes involved in postulated pathological mechanisms of DBN (i.e., impaired function of cerebellar PCs). [ABSTRACT FROM AUTHOR]

Autoimmune disorders affecting the vestibular end organs, vestibular pathways, vestibular nuclei, and vestibulocerebellum are often underrecognized as a cause of chronic dizziness and ataxia. Autoantibodies specific for cell-surface, synaptic, and intracellular neural antigens serve as biomarkers of these disorders. This article describes the epidemiology, clinical presentation, diagnostic considerations, imaging findings, treatment, and prognosis of autoimmune disorders, in which the vestibulocerebellar syndrome is the main or presenting clinical presentation. Antibodies specific for intracellular antigenic targets described in the article are PCA-1 (Purkinje cell cytoplasmic antibody type 1, also known as anti-Yo), ANNA-1 (antinuclear neuronal antibody type 1, also known as anti-Hu), ANNA-2 (antinuclear neuronal antibody type 2, also known as anti-Ri), Ma1/2 (anti-Kelch-like 11/12 antibody), Kelch-like 11, amphiphysin, CV2 (collapsin response 2, also known as collapsin response mediator protein-5 [CRMP5]), VGCC (voltage-gated calcium channel), GAD65 (glutamic acid decarboxylase 65-kDa isoform), AP3B2 (adaptor protein 3B2, also known as anti-Nb), MAP1B (microtubule-associated protein 1B antibody, also known as anti-PCA-2), and neurochondrin antibodies. Antibodies targeting cell-surface or synaptic antigenic targets described in the article include DNER (delta/notchlike epidermal growth factor related receptor; antigen to anti-Tr), CASPR2 (contactin-associated proteinlike 2), septin-5, Homer-3, and mGluR1 (metabotropic glutamate receptor 1). The vestibulocerebellar presentation is largely indistinguishable among these conditions and is characterized by subacute onset of cerebellar symptoms over weeks to months. The diagnosis of autoimmune vestibulocerebellar syndromes is based on a combination of clinical and serological features, with a limited role for neuroimaging. Subtle eye movement abnormalities can be an early feature in many of these disorders, and therefore a meticulous vestibulo-ocular examination is essential for early and correct identification. Cancer occurrence and its type are variable and depend on the autoantibody detected and other cancer risk factors. Treatment comprises immunotherapy and cancer-directed therapy. Acute immunotherapies such as intravenous immunoglobulin, plasma exchange, and steroids are used in the initial phase, and the use of long-term immunosuppression such as rituximab may be necessary in relapsing cases. Outcomes are better if immunotherapy is started early. The neurologic prognosis depends on multiple factors. [ABSTRACT FROM AUTHOR]

Cerebellar dizziness and vertigo account for approximately 10% of diagnoses in a tertiary dizziness center. This term summarizes a large group of disorders with chronic (degenerative, hereditary, acquired cerebellar ataxias), recurrent (episodic ataxias), or acute (stroke, inflammation) presentations. Key to the diagnosis is a comprehensive examination of central ocular motor and vestibular function. Patients with cerebellar dizziness and vertigo usually show a pattern of deficits in smooth pursuit, gaze-holding, saccade accuracy, or fixation-suppression of the vestibulo-ocular reflex. Central fixation nystagmus (e.g., downbeat nystagmus), gaze-evoked nystagmus, central positional nystagmus, or head-shaking nystagmus with cross-coupling (i.e., horizontal head shaking causing inappropriate vertical nystagmus) occurs frequently. Overlap syndromes with peripheral vestibular disorders, such as cerebellar ataxia, neuropathy, and vestibular areflexia, exist rarely. Posturography and gait analysis can contribute to diagnostic differentiation, estimation of the risk of falls, as well as quantification of progression and treatment effects. Patients with cerebellar dizziness and vertigo should receive multimodal treatment, including balance training, occupational therapy, and medication. [ABSTRACT FROM AUTHOR]