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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 −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 −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).

A 60-year-old patient had progressive imbalance. Examination revealed saccadic smooth pursuit, downbeat nystagmus, ataxia of stance and gait, and reduced vibration sense. Video head impulse and caloric testing both showed vestibulo-ocular reflex (VOR) deficits (figure). The patient has cerebellar ataxia with neuronopathy and vestibular areflexia syndrome.1,2 Slow head turns while looking at an earth-fixed target produce saccadic rather than smooth compensatory eye movements (Videos 1) due to impairment of both the VOR and smooth pursuit (the visually enhanced VOR): 1 simple bedside test, 2 clinical signs, and 1 precise diagnosis.

Purpose This study aimed to report an unusual case of benign paroxysmal positional vertigo (BPPV), who showed prolonged positional downbeat nystagmus without latency and was diagnosed with cupulolithiasis of the anterior canal (AC). We compared this case with one of typical AC-BPPV, and possible mechanisms underlying the atypical characteristics were discussed. Method Two patients diagnosed with AC-BPPV were reported. Positional testing using video-oculography goggles was performed, and outcomes were measured via medical records and analysis of videos of the nystagmus. Results Downbeat nystagmus was observed in the contralateral Dix–Hallpike test in both cases. The torsional component was subtle or absent, but motion was induced toward the affected ear. The two cases differed in latency and duration of vertigo, as well as habituation. The patient with atypical nystagmus showed little or no latency and longer duration. Moreover, there was no habituation on repeated tests. The nystagmus showed several differences from that of typical AC-BPPV. Conclusions Based on our case, AC-BPPV may induce various unusual clinical manifestations of nystagmus. Accurate diagnosis requires careful consideration of the patient's symptoms and the characteristics of the nystagmus. Supplemental Material https://doi.org/10.23641/asha.14265356

A 45-year-old man with a history of testicular seminoma treated 8 years earlier presented with chronic progressive truncal and limb ataxia, progressive sensorineural hearing loss, and episodic vertigo. Eye movement and neuro-otology examinations showed localizing abnormalities to the bilateral cerebellar flocculus, vermis, and bilateral cerebellar hemispheres. Audiometric testing showed bilateral symmetric sensorineural hearing loss. There was a normal MRI of the brain. Cerebrospinal fluid (CSF) showed modest lymphocytic pleocytosis, and there was an elevated serum choriogonadotrophic hormone. An abdominal CT scan showed a solitary, large retroperitoneal lymph node, and histopathologic examination of the node biopsy showed granulomatous inflammation without microorganisms; eventually, immunohistochemical markers confirmed the diagnosis of metastatic seminoma. Although normal neuroimaging and inflammatory CSF reaction suggested a paraneoplastic etiology, the initial paraneoplastic antibody testing was negative. Subsequent investigation identified a positive kelch-11 protein antibody, thus confirming the paraneoplastic connection between the metastatic seminoma and the subacute neurologic-cochleovestibular syndrome.

Objective Though fluctuations in vestibular function represent a common finding in Meniere's disease, we describe how benign paroxysmal positional vertigo (BPPV) may result in fluctuations of vestibulo-ocular reflex for the involved canal depending on the disposition of otoliths. Patient A 54-year-old woman suffering from refractory posterior canal (PC)-BPPV resulting in fluctuating PC function. Interventions Diagnostic evaluation and rehabilitative treatment for BPPV involving the affected PC. Main outcome measures Video-Frenzel and video-head impulse test (vHIT) findings before and after canalith repositioning procedures for PC-BPPV. Results BPPV involving the nonampullary arm of right PC was diagnosed based on presenting positional downbeat nystagmus and selective right PC hypofunction at the vHIT. During physical treatment, nystagmus first became positional paroxysmal upbeat likely due to a shift of debris into the ampullary arm of the canal, then turned to spontaneous downbeat nystagmus consistently with a plug effect exerted by particles entrapped within the nonampullary arm of PC and finally receded proving an otoliths fall within the utriculus. Simultaneously, vHIT documented fluctuations for right PC vestibulo-ocular reflex gain as it first increased to normal values, then severely declined and finally normalized, respectively. High-resolution computed tomography scan detected ipsilateral superior canal dehiscence. Conclusions In accordance with recently reported vHIT findings in different types of BPPV, fluctuation of PC function could be likely explained by the effect of particles on cupular dynamic responses depending on the portion of the canal gradually involved. Superior canal dehiscence may have played a role facilitating otoliths mobilization by reducing labyrinthine impedance.

The Y-group plays an important role in the generation of upward smooth pursuit eye movements and contributes to the adaptive properties of the vertical vestibulo-ocular reflex. Malfunction of this circuitry may cause eye movement disorders, such as downbeat nystagmus. To characterize the neuron populations in the Y-group, we performed immunostainings for cellular proteins related to firing characteristics and transmitters (calretinin, GABA-related proteins and ion channels) in brainstem sections of macaque monkeys that had received tracer injections into the oculomotor nucleus. Two histochemically different populations of premotor neurons were identified: The calretinin-positive population represents the excitatory projection to contralateral upgaze motoneurons, whereas the GABAergic population represents the inhibitory projection to ipsilateral downgaze motoneurons. Both populations receive a strong supply by GABAergic nerve endings most likely originating from floccular Purkinje cells. All premotor neurons express nonphosphorylated neurofilaments and are ensheathed by strong perineuronal nets. In addition, they contain the voltage-gated potassium channels Kv1.1 and Kv3.1b which suggests biophysical similarities to high-activity premotor neurons of vestibular and oculomotor systems. The premotor neurons of Y-group form a homogenous population with histochemical characteristics compatible with fast-firing projection neurons that can also undergo plasticity and contribute to motor learning as found for the adaptation of the vestibulo-ocular reflex in response to visual-vestibular mismatch stimulation. The histochemical characterization of premotor neurons in the Y-group allows the identification of the homologue cell groups in human, including their transmitter inputs and will serve as basis for correlated anatomical-neuropathological studies of clinical cases with downbeat nystagmus.

Early identification of cardiogenic vertigo (CV) is necessary to prevent serious complications of cardiovascular diseases. However, the literature is limited to case reports without detailed clinical features or diagnostic criteria. The aim of this study was to define characteristics of CV and propose diagnostic criteria. This study included patients with CV diagnosed at Pusan National University and Keimyung University Hospitals. Demographic, clinical, laboratory, and treatment data were analyzed. Of 72 patients with clinically suspicious CV, 27 were finally included. The age ranged from 63 to 88 years (75.1 ± 7.2 years). Recurrent vertigo occurred without syncopal attacks in 52% [95% CI, 32–71], while it preceded (37% [19–58]) or followed (11% [2–29]) syncope. The patients with recurrent isolated vertigo had suffered from symptoms from 15 days to 5 years until final diagnosis (median 122 days). The vertigo lasted only for a few seconds (93% [76–99]) or a few minutes (7% [1–24]). Fourteen patients presented with spinning vertigo, and one of them showed spontaneous downbeat nystagmus during the attack. Accompanying symptoms including chest discomfort, palpitation, headache, arm twitching, and lightheadedness were found in 70% [50–86]. Between patients with and without syncope, there was no difference in clinical parameters and results of cardiac function tests. The most common cardiac abnormality during the attacks of vertigo was bradyarrhythmia (89% [71–98]). Cardiovascular diseases can develop recurrent isolated vertigo without or preceding syncope. Onset age, duration of vertigo, accompanying symptoms, and underlying cardiac diseases can aid in differentiation from other vestibular disorders. Early identification of CV would reduce morbidity and mortality associated with cardiac syncope.

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.

A 42-year-old previously healthy woman developed sudden right hearing loss, vertigo, and nausea. She had a dull and compressing sensation in the right ear but denied any significant headache or neck pain. She had no medical history including vascular risk factors and neuro-otologic disorders and denied a recent history of head and neck trauma. Review of systems was unremarkable. Neurologic examination showed a small spontaneous downbeat nystagmus only in darkness without visual fixation. The downbeat nystagmus increased after horizontal head-shaking and in the straight-head hanging position. There was neither gaze-evoked nystagmus nor skew deviation. Bedside horizontal head impulse tests (HITs) and other neurologic examinations were also normal. Pure tone audiometry documented a profound sensorineural hearing loss (SNHL) in the right ear with a pure tone average at 100 dB (figure, A). Video-HITs showed normal head impulse gains for all 6 semicircular canals (SCCs) but small covert saccades for right posterior SCC. The results of bithermal caloric tests, cervical and ocular vestibular-evoked myogenic potentials, and measurements of subjective visual vertical were normal.

Background: There is no authorized treatment for ataxia telangiectasia (AT). As cerebellar symptoms of storage diseases were improved by acetyl-DL-leucine (ADLL), the authors hypothesized a symptomatic and disease-modifying effect in AT upon supplementation with ADLL. Methods: Six patients were treated with ADLL 3 g/day for 1 week followed by 5g/day for 3 weeks to 1 year. Cerebellar ataxia was evaluated by validated scales. Gaze-holding, saccades and smooth pursuit were examined by video-oculography. Measurements took place at baseline, at 1 month of therapy in 5 patients, and after 6 and 12 months in 1 patient. Results: The Scale for Assessment and Rating of Ataxia changed from the baseline, mean, (SD, min-max) of 22.1 (5.88, 11-28.5) to 18 points (5.39, 8.5-23.5) after 1 month on medication ( P = .0028). All patients demonstrated gaze-holding deficits; 3 patients had central-position downbeat-nystagmus. Mean slow-phase velocity of this nystagmus with the gaze straight-ahead changed from 5.57°/s (1.8, 3.53-6.99) to 4.7°/s (0.79, 3.97-5.56) after 1 month on treatment (1.35, -2.56-4.17) ( P = .046). Interpretation: ADLL may improve ataxia and ocular stability in AT patients, while the molecular basis still remains to be elucidated. A multicentric, rater-blinded, phase II trial currently investigates the effects of acetyl-L-leucine in AT (NCT03759678).

Eye movement abnormalities due to urgent or emergent etiologies in the field of movement disorders include acute/subacute onset supranuclear saccadic gaze palsies, ocular flutter and opsoclonus, various types of nystagmus, and oculogyric crisis. Supranuclear saccadic gaze palsies, from failure of brainstem supranuclear saccadic burst neurons, cause slowing of saccades (horizontally and/or vertically) with or without range of motion limitation of eye movements. Acute/subacute causes of saccadic gaze palsies include vascular, neoplastic/paraneoplastic, infectious, and inflammatory etiologies. Ocular flutter and opsoclonus are erratic bursts of high frequency, rapid saccades that oscillate about the midline of the visual axis with no intersaccadic interval. Flutter occurs only in the horizontal plane, while opsoclonus occurs in all trajectories. Ocular flutter and opsoclonus typically occur either in infectious/para-infectious brainstem encephalitis or paraneoplastic/autoimmune disease. Nystagmus is a rhythmic biphasic oscillation of the eyes, initiated by a slow drift of the eyes. Downbeat nystagmus may occur acutely or subacutely from ischemic or paraneoplastic cerebellar disorders. Upbeat nystagmus is common in Wernicke encephalopathy and may occur from a brainstem stroke. Pendular nystagmus from oculopalatal myoclonus is not an emergency, but may be mistaken for a recurrent brainstem stroke. Oculogyric crisis is an acute dystonic reaction of extraocular muscles with a conjugate deviation of the eyes, typically upward. Oculogyric crises are most commonly acute or tardive reactions to neuroleptics, although other etiologies exist.

Purpose of review This review will extensively cover the clinical manifestations, causes, diagnostic evaluation, and management strategies of downbeat nystagmus (DBN). Recent findings Historically, MRI to assess for structural lesions at the cervicomedullary junction has been the primary diagnostic test in the evaluation of DBN since the 1980s. In recent years, there is increasing awareness of nonstructural causes of DBN including gluten ataxia, nutritional deficiencies, and paraneoplastic syndromes, among others. Medical management with aminopyridines has become first-line therapy in addition to disease-specific therapies. Summary DBN is a common form of acquired nystagmus and the differential diagnosis remains broad, including both benign and potentially fatal causes. For practical purposes, the causes can be categorized as structural vs. nonstructural with MRI as the ideal, initial diagnostic study to differentiate the two. General therapeutic options include pharmacotherapy to enhance Purkinje cell function, strabismus surgery or prisms to shift null points, and behavioural changes. Disease-specific treatment is necessarily broad, though a significant proportion of patients will be idiopathic.

Background Spontaneous downbeat nystagmus is a finding that raises suspicions of a central nervous system disorder. Vermis and lower brainstem lesions are considered to be responsible, but the exact mechanism is still controversial. We observed a rare case of spontaneous downbeat nystagmus caused by an infratentorial meningioma. Case Description A 50-year-old woman was incidentally diagnosed with infratentorial tumor. Later, she suffered from oscillopsia and the symptom disturbed her daily life especially while driving. Magnetic resonance imaging showed a tumor of approximately 30 mm in diameter at the dorsal midline of the posterior fossa. The tumor was compressing the cerebellar vermis and was apparently responsible for the symptoms that affected her daily life; therefore, we decided to perform tumor removal. The postoperative course was uneventful, and the spontaneous downbeat nystagmus completely disappeared. Conclusions Vertical nystagmus is a finding that raises suspicion of a central nervous system disorder, and requires detailed examination. In addition, in case of vertical nystagmus because of tumor compression of the vermis, removal of the tumor can be an effective treatment.

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.

We report atypical opsoclonus in a patient with multiple system atrophy and propose a mechanism based on the patterns of modulation by visual, vestibular, and saccadic and vergence stimulation. Firstly, the 6-Hz opsoclonus mostly in the vertical plane occurred only after the development of downbeat nystagmus in darkness without visual fixation. Even after a substantial build-up, visual suppression of the opsoclonus was immediate and complete. Furthermore, the latency for re-emergence of opsoclonus in darkness was greater when the duration of preceding visual fixation was longer. Secondly, the effect of preceding downbeat nystagmus on the development of opsoclonus was evaluated by changing the head position. The opsoclonus did not occur in the supine position when the downbeat nystagmus was absent. After horizontal head shaking, the opsoclonus in the vertical plane gradually evolved into horizontal plane and resumed its vertical direction again after vertical head shaking. Thirdly, any opsoclonus was not triggered by imaginary saccades in the supine position. Lastly, combined vergence and saccadic eye movements during the Muller paradigm did not induce opsoclonus. From these findings of modulation, we suggest that the opsoclonus observed in our patient was invoked by vestibular signals. When the function of the omnipause neurons and saccadic system was impaired, the centrally mediated vestibular eye velocity signals may activate the saccadic system to generate opsoclonus. These atypical patterns of opsoclonus, distinct from the classic opsoclonus frequently observed in para-neoplastic or para-infectious disorders, may be an unrevealing sign of degenerative brainstem or cerebellar disorders.

RESUMEN El downbeat nystagmus o nistagmo vertical hacia abajo es el nistagmo de fijación adquirido más frecuente, que en la mayoría de los casos es causado por patología a nivel del sistema nervioso central que genera disrupción del control inhibitorio del flóculo y paraflóculo cerebeloso sobre los núcleos vestibulares. Entre sus causas se encuentran enfermedades neurodegenerativas y vasculares de cerebelo o tronco cerebral, tumores y traumas, pero cerca del 40% de los casos son idiopáticos y hasta la mitad de los pacientes presentan estudio imagenológico negativo. En este artículo presentamos dos casos que consultaron en el Servicio de Otorrinolaringología del Hospital Clínico de la Universidad de Chile.

Aim To report the effect of oval and round window reinforcement surgery performed in two patients with the Tullio phenomenon. Case 1: A male with bilateral superior canal dehiscence syndrome. Downbeat nystagmus with leftward horizontal eye movement was recorded in an electronystagmogram using a pure-tone sound of 110 dB at 2000 or 4000 Hz in the right ear. Case 2: A female who had undergone stapes surgery. Computed tomography revealed an ossicular prosthesis in the vestibule. An audiogram indicated mild to moderate hearing impairment in the right ear. Leftward horizontal nystagmus was recorded in an electronystagmogram using a pure-tone sound of 110 dB at 500 or 1000 Hz in the right ear. Surgical findings indicated that the prosthesis was inserted deep into the oval window, which was closed with thin connective tissue. Outcomes After oval and round window reinforcement surgery was performed in the right ear, and loud, pure-tone sounds elicited neither nystagmus nor dizziness in either patient.

A 58-year-old man presented with 1 month subacute onset of instability, oscillopsia, vertigo, nausea, and vomiting. Neurologic examination revealed gaze-evoked and prominently downbeat nystagmus, left eyelid ptosis, and gait cerebellar ataxia (Videos 1 and Videos 2). There was no dysarthria or dysmetria. Head MRI was unremarkable and lumbar puncture showed mild lymphocyte predominant pleocytosis with normal proteins. EMG showed no abnormalities. Cancer was not identified. Serum and CSF septin-5–specific immunoglobulin G was identified by rat cerebellar immunohistochemistry and confirmed with in-house cell-based assay (HEK293 cells transfected with human Sep5) and Western blot (Figure).1,2 Immunotherapy using corticosteroids, IV immunoglobulin, cyclophosphamide, and rituximab showed minimal improvement.

A 58-year-old man developed subacute gait instability, oscillopsia, and vertigo. Examination showed gait ataxia and periodic alternating nystagmus (PAN) (video). MRI revealed T2 hyperintensities in the left cerebellum and nodulus (figure). CSF was inflammatory. Autoantibody evaluation was positive for Kelch-like protein 11 (KLHL11) in serum and CSF by tissue-based immunofluorescence assay and cell-based assay, prompting identification of a retroperitoneal mass by CT imaging consistent with seminoma.1 PAN resolved after plasma exchange, corticosteroids, adjuvant chemotherapy, and symptomatic baclofen; downbeat nystagmus persisted.2 KLHL11 immunoglobulin G is associated with testicular germ cell tumor paraneoplastic rhomboencephalitis. Early identification is crucial as immunotherapy and cancer treatment can prevent neurologic dysfunction.2

Nystagmus is an involuntary, rhythmic ocular movement that is initiated by a slow drift and comes in two varieties (Fig. 16.1): (1) jerk nystagmus (alternating slow and fast phases) and (2) pendular nystagmus (back-to-back slow phases). Both jerk and pendular nystagmus can have horizontal, vertical, or torsional components in isolation or combination. Some nystagmus manifests very early in life (infantile), while acquired nystagmus can be associated with a variety of pathologic conditions. Acquired nystagmus becomes symptomatic when the pathologic slow phase moves the eyes away from fixation, often causing oscillopsia, or an illusory movement of a stationary object. Therapies proposed for nystagmus include pharmacologic, chemodenervation (e.g., botulinum toxin), surgical, and optical among others. The goal of treatment is to improve vision by stabilizing retinal images. While large-scale randomized controlled trials are generally lacking for the treatment of nystagmus, we will discuss those therapies for which at least some evidence exists.

Background Bow Hunter’s Syndrome (BHS) is known as one of cervical diseases which causes vertigo, but the details of its vertigo, especially nystagmus and eye movement, are still incompletely understood. This time, we reported the first case of BHS with a nystagmus chart with video record of transitional nystagmus. Case presentation The patient, a 47-year-old female, complained of vertigo caused by head rotation. When she turned her head leftward, leftward nystagmus appeared, and this was followed by dullness of the right arm. After her head was returned to the central position, downbeat nystagmus appeared, which changed to rightward nystagmus. She was diagnosed with BHS by her symptoms and images. We recorded a nystagmus video and nystagmus chart of this transitional nystagmus including downbeat nystagmus. Her vertigo was cured by the modification of a prescription for her past medical history: hypertension. Conclusion The vertigo of BHS accompanies nystagmus. In this present case, the transitional nystagmus was observed, and it occurred toward the healthy side. Then the nystagmus direction was changed to the affected side via downbeat nystagmus. This is the first report with both a nystagmus chart with video of BHS. Nowadays, various kinds of vertigo induced by neck movement are known. BHS is a rare disease among vertigo diseases, but we should consider it as a different diagnosis of vertigo patients. A precise interview and proper examination are required to make the final diagnosis.

We present the case of a 65-year-old patient who suffered a wake-up brainstem stroke. The only symptom reported by the patient was double vision. Upon examination, she was found to have left internuclear ophthalmoplegia and ipsilateral downbeat nystagmus. Magnetic resonance angiography revealed a unilateral partial fetal posterior cerebral artery and unilateral posterior communicating artery hypoplasia. The patient was ineligible for intravenous thrombolysis: she evolved favorably with anti-platelet medication and was discharged after five days. We put forth a discussion on the clinical significance of these physical exams and magnetic resonance imaging findings.

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

Background Paraneoplastic cerebellar degeneration (PCD) is a devastating paraneoplastic syndrome that occasionally occurs in patients with Hodgkin lymphoma (HL). Anti-Ma2 is a well-characterized onconeuronal antibody and one of the causes of PCD. There has been only one previous report of anti-Ma2-associated paraneoplastic syndrome as a complication of HL. Here we present a rare case of anti-Ma2-associated PCD in a patient with nodular lymphocyte-predominant HL (NLPHL). Case presentation A 77-year-old man with a 3-month history of gait instability and a 2-month history of oscillopsia was referred to our hospital for further investigation. On examination, his cognition was normal. He had nystagmus in all directions of gaze; specifically, he had horizontal and rotatory nystagmus in the primary position, downbeat nystagmus after right, left, and up gaze, and upbeat nystagmus after down gaze. Although his limb ataxia was mild, his trunk ataxia was so pronounced that he was unable to walk without support. We strongly suspected paraneoplastic syndrome and tested for neuronal autoantibodies. The anti-Ma2 antibody was strongly positive in the blood and cerebrospinal fluid but other antineuronal autoantibodies were negative. Computed tomography showed an enlarged lymph node in the right axilla but no masses. Biopsy confirmed a diagnosis of NLPHL. The NLPHL cells stained with anti-Ma-2 antibody in the cytoplasm, suggesting these abnormal cells contained protein that was cross-reactive with Ma-2. Conclusions To the best of our knowledge, this is the first case of anti-Ma2-associated PCD in a patient with NLPHL that was confirmed using immunostaining of the lymph node tissue with anti-Ma2 antibody. Our case confirms an association between anti-Ma2-associated PCD and NLPHL.

False localizing signs (FLS) and other misleading neurological signs have long been an intractable aspect of neurocritical care. Because they suggest an incorrect location or etiology of the pathological lesion, they have often led to misdiagnosis and mismanagement of the patient. Here, we reviewed the existing literature to provide an updated, comprehensive descriptive review of these difficult to diagnose signs in neurocritical care. For each sign presented, we discuss the non-false localizing presentation of symptoms, the common FLS or misleading presentation, etiology/pathogenesis of the sign, and diagnosis, as well as any other clinically relevant considerations. Within cranial neuropathies, we cover cranial nerves III, IV, V, VI, VII, VIII, as well as multiple cranial nerve involvement of IX, X, and XII. FLS ophthalmologic symptoms indicate diagnostically challenging neurological deficits, and here we discuss downbeat nystagmus, ping-pong-gaze, one-and-a-half syndrome, and wall-eyed bilateral nuclear ophthalmoplegia (WEBINO). Cranial herniation syndromes are integral to any discussion of FLS and here we cover Kernohan's notch phenomenon, pseudo-Dandy Walker malformation, and uncal herniation. FLS in the spinal cord have also been relatively well documented, but in addition to compressive lesions, we also discuss newer findings in radiculopathy and disc herniation. Finally, pulmonary syndromes may sometimes be overlooked in discussions of neurological signs but are critically important to recognize and manage in neurocritical care, and here we discuss Cheyne-Stokes respiration, cluster breathing, central neurogenic hyperventilation, ataxic breathing, Ondine's curse, and hypercapnia. Though some of these signs may be rare, the framework for diagnosing and treating them must continue to evolve with our growing understanding of their etiology and varied presentations.

To report clinical and ancillary findings in a kindred with spinocerebellar ataxia 38 (SCA38). 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. 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. 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.

ObjectiveTo determine the mechanism of ictal downbeat nystagmus in Ménière disease (MD), we compared the head impulse gain of the vestibulo-ocular reflex (VOR) for each semicircular canal between patients with (n = 7) and without (n = 70) downbeat nystagmus during attacks of MD.MethodsWe retrospectively analyzed the results of video-oculography, video head-impulse tests, and cervical vestibular-evoked myogenic potentials (VEMPs) in 77 patients with definite MD who were evaluated during an attack.ResultsPure or predominant downbeat nystagmus was observed in 7 patients (9%) with unilateral MD during the attacks. All 7 patients showed spontaneous downbeat nystagmus without visual fixation with a slow phase velocity ranging from 1.5 to 11.2°/s (median 5.4, interquartile range 3.7–8.5). All showed a transient decrease of the head impulse VOR gains for the posterior canals (PCs) in both ears (n = 4) or in the affected ear (n = 3). Cervical VEMPs were decreased in the affected (n = 2) or both ears (n = 2) when evaluated during the attacks. Downbeat nystagmus disappeared along with normalization of the VOR gains for PCs after the attacks in all patients. During the attacks, the head impulse VOR gains for the PC on the affected side were lower in the patients with ictal downbeat nystagmus than in those without (Mann-Whitney U test, p < 0.001), while the gains for other semicircular canals did not differ between the groups.ConclusionDownbeat nystagmus may be observed during attacks of MD due to an asymmetry in the vertical VOR or saccular dysfunction. MD should be considered in recurrent audiovestibulopathy and ictal downbeat nystagmus.

Cerebellar ataxia is a frequent and often disabling syndrome severely impairing motor functioning and quality of life. Patients suffer from reduced mobility, and restricted autonomy, experiencing an even lower quality of life than, e.g., stroke survivors. Aminopyridines have been demonstrated viable for the symptomatic treatment of certain forms of cerebellar ataxia. This article will give an outline of the present pharmacotherapy of different cerebellar disorders. As a current key-therapy for the treatment of downbeat nystagmus 4-aminopyridine (4-AP) is suggested for the treatment of downbeat nystagmus (5–10 mg Twice a day [TID]), a frequent type of persisting nystagmus, due to a compromise of the vestibulo-cerebellum. Studies with animals have demonstrated, that a nonselective blockage of voltage-gated potassium channels (mainly Kv1.5) increases Purkinje- cell (PC) excitability. In episodic ataxia type 2 (EA2), which is frequently caused by mutations of the PQ-calcium channel, the efficacy of 4-AP (5–10 mg TID) has been shown in a randomized controlled trial (RCT). 4-AP was well tolerated in the recommended dosages. 4-AP was also effective in elevating symptoms in cerebellar gait ataxia of different etiologies (2 case series). A new treatment option for cerebellar disease is the amino-acid acetyl-DL-leucine, which has significantly improved cerebellar symptoms in three case series. There are on-going randomized controlled trials for cerebellar ataxia (acetyl-DL-leucine vs placebo; ALCAT), cerebellar gait disorders (SR-form of 4-AP vs placebo; FACEG) and EA2 (sustained-release/SR-form of 4-AP vs acetazolamide vs placebo; EAT2TREAT), which will provide new insights into the pharmacological treatment of cerebellar disorders.

ObjectiveTo determine the prevalence of central lesions in persistent geotropic positional nystagmus, and characteristics and anatomical substrates of the nystagmus in cerebellar lesions.MethodsWe prospectively recruited 58 patients with persistent geotropic positional nystagmus at the Dizziness Clinic of Pusan National University Hospital. Seven patients with unilateral cerebellar lesions were subjected to analysis of clinical characteristics, oculographic data, and MRI lesions. For comparison, we studied 37 cases of peripheral persistent geotropic positional nystagmus.ResultsThe prevalence of central lesions in persistent geotropic positional nystagmus was 12% (7/58). Persistent geotropic positional nystagmus in cerebellar lesions was mostly asymmetrical. Horizontal nystagmus changed in direction during the bow-and-lean test with null positions. All patients showed impaired horizontal smooth pursuit bilaterally, and 3 of them also had positional downbeat nystagmus. The peak intensity and asymmetry of persistent geotropic positional nystagmus did not differ between central and peripheral groups (p > 0.05), while there was a difference in the maxima. Lesion overlays revealed that damage to the cerebellar tonsil was responsible for the generation of persistent geotropic positional nystagmus.ConclusionAlthough persistent geotropic positional nystagmus in cerebellar lesions shares the characteristics of nystagmus measures with peripheral cases, accompanying central oculomotor signs can aid in differentiation. In tonsillar lesions, compensatory rotational feedback due to erroneous estimation of the direction of gravity may generate constant horizontal geotropic positional nystagmus.

Background Bow hunter's syndrome (BHS) is rare and typically induced by mechanical compression of the dominant vertebral artery (VA) during head rotation. We report a case of BHS induced by nondominant VA compression in which contralateral VA patency was preserved. Definite diagnosis of BHS is not often feasible because of transient symptoms and nonspecific clinical features, such as vertigo or dizziness, especially in nondominant VA compression. We discuss the diagnostic clues of BHS and clinical features of BHS caused by nondominant VA compression through a literature review. Case Description A 65-year-old man suffered repeated bouts of dizziness whenever his head was rotated to the left. This dizziness was consistently accompanied by downbeat nystagmus (DBN). Radiography revealed left VA compression by a lateral osteophyte at the C3-C4 level only during left head rotation. In contrast, patency of the right VA, which was almost equivalent in size to the left VA, was preserved during head rotation. The distinctive clinical finding of head rotation-induced DBN, which is usually associated with lesions involving the caudal midline cerebellum, was observed. Symptoms disappeared immediately after left VA decompression with osteophytectomy and C3-C4 fusion. Conclusions Despite excellent flow through the contralateral VA, occlusion of the nondominant VA occasionally induces BHS. According to a review of the literature, BHS cases do not always depend on the VA on one side for blood supply. Head rotation–induced DBN can be useful for diagnosis of BHS, even in cases of nondominant VA compression.

Atypical motor neurone disease (MND) represents a challenging and expanding group of neurodegenerative disorders involving the upper or lower motor neurones, and rarely both. Neuro-ophthalmological disturbances such as gaze-evoked downbeat nystagmus are extremely rare in the context of typical and atypical MND. Finger extension weakness and downbeat nystagmus motor neurone disease (FEWDON-MND) syndrome has been recently recognised as a distinct syndromic phenotype of MND, with a characteristic clinical picture. We describe a 63-year-old woman with long-standing lower motor neurone involvement of the upper limbs, who on examination had gaze-evoked downbeat nystagmus. After extensive negative investigation for secondary causes of MND and downbeat nystagmus, we diagnosed FEWDON-MND syndrome.

This paper presents diagnostic criteria for persistent postural-perceptual dizziness (PPPD) to be included in the International Classification of Vestibular Disorders (ICVD). The term PPPD is new, but the disorder is not. Its diagnostic criteria were derived by expert consensus from an exhaustive review of 30 years of research on phobic postural vertigo, space-motion discomfort, visual vertigo, and chronic subjective dizziness. PPPD manifests with one or more symptoms of dizziness, unsteadiness, or non-spinning vertigo that are present on most days for three months or more and are exacerbated by upright posture, active or passive movement, and exposure to moving or complex visual stimuli. PPPD may be precipitated by conditions that disrupt balance or cause vertigo, unsteadiness, or dizziness, including peripheral or central vestibular disorders, other medical illnesses, or psychological distress. PPPD may be present alone or co-exist with other conditions. Possible subtypes await future identification and validation. The pathophysiologic processes underlying PPPD are not fully known. Emerging research suggests that it may arise from functional changes in postural control mechanisms, multi-sensory information processing, or cortical integration of spatial orientation and threat assessment. Thus, PPPD is classified as a chronic functional vestibular disorder. It is not a structural or psychiatric condition.

ABSTACT 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

A 65-year-old woman with right-sided Meniere disease experienced one of her usual and frequent acute vertigo attacks during eye movement recording (video 1). The attacks were associated with right-sided tinnitus, hearing loss, and vomiting. She initially demonstrated right-beating nystagmus, but after 2 minutes, the nystagmus gradually reversed and became left-beating (video 1). During the reversal, downbeat nystagmus was present temporarily. The left-beating nystagmus then persisted for 2 hours.

Objective To describe the possible diagnostic role of video-head impulse test (vHIT) in patients presenting with positional downbeat nystagmus (PDN) due to benign paroxysmal positional vertigo (BPPV) involving the anterior canal (AC) or the non-ampullary arm of the posterior canal (PC). Patients Three patients presenting with positional vertigo, PDN, symmetrical cervical and ocular vestibular-evoked myogenic potentials, and selective deficit of the vestibulo-ocular reflex (VOR) gain for a single vertical canal on vHIT. Interventions Diagnostic evaluation and rehabilitative treatment for BPPV involving the deficient canals. Main outcome measures Video-oculographic and vHIT findings before and after canalith repositioning procedures (CRP) for AC-BPPV and apogeotropic PC-BPPV. Results Each patient was treated with CRP for BPPV involving the hypoactive canal. In one case, symptoms receded with physical therapy, whereas two patients developed a paroxysmal positional upbeat nystagmus consistent with BPPV involving the ampullary arm of the ipsilateral PC and were treated with Epley CRP. Posttreatment evaluation showed resolution of symptoms and signs and restitution of canal function in all cases. Conclusions PDN can be due to both peripheral and central vestibular pathologies. In case of BPPV, involvement of the non-ampullary arm of the PC is hardly distinguishable from contralateral AC canalolithiasis. In these situations, vHIT may play a key role in the differential diagnosis. Considering these findings, we propose to include vHIT in the test battery of patient with PDN, as it may provide clues to the differential diagnosis with central pathologies enabling the identification of the canal involved by BPPV.

Background Lithium salts have been commonly used for prophylaxis and treatment of bipolar disorder and have numerous side effects. However, there has been no report of skew deviation and downbeat nystagmus associated with lithium. Herein, we report the first case of lithium-induced skew deviation and downbeat nystagmus. Case presentation A 39 years-old woman presented with intermittent vertical diplopia and dizziness within 1–2 months. Ophthalmologic examination revealed downbeat nystagmus and 6 prism diopters of right hypertropia. Funduscopic examination showed mild incyclotorsion on right eye. However, ductions and versions were within normal range. Other neurological examinations were also normal. She had a history of bipolar disorder treated with daily 600-900 mg of lithium for past 6 years, and 2 months before the first visit, daily dose of lithium was increased to 1200 mg. We referred the patients to psychiatrist. Although the serum level of lithium was within the normal therapeutic range, her daily dose of lithium was reduced to 600 mg and then stopped. 6 days after cessation of lithium, down beat nystagmus and right hypertropia were completely resolved and symptoms did not recur over a year. Conclusion Even within a normal therapeutic range, downbeat nystagmus and skew deviation can occur as side effect of lithium. Dehydration may contribute to the neurotoxicity of lithium.

Purpose of review This article provides an overview of nystagmus and saccadic intrusions with the goal of facilitating recognition and differentiation of abnormal eye movements to assist with accurate diagnosis of neurologic disease and evidence-based specific treatment of oscillopsia. Myriad advances have been made in the understanding of several types of nystagmus and saccadic intrusions, even in the past 5 to 10 years, especially regarding underlying pathophysiology, leading to pharmacologic advances rooted in physiologic principles. Recent findings Specific recent advances in the study of nystagmus and saccadic intrusions include (1) improved understanding of the underlying etiologies and mechanisms of nystagmus enhanced or unmasked by provocative maneuvers such as supine position or head shaking; (2) recognition of the differences in behavior and treatment responsivity of acquired pendular nystagmus in demyelinating disease versus oculopalatal myoclonus; (3) recognition that oculopalatal myoclonus results from a dual mechanism of abnormal inferior olivary gap junction connection formation and maladaptive cerebellar learning; and (4) well-controlled clinical trials to evaluate the efficacy of pharmacologic interventions, such as memantine for acquired pendular nystagmus and 4-aminopyridine for downbeat nystagmus. Summary Accurate recognition of nystagmus and saccadic intrusions, including familiarity with the subtleties of examination techniques that allow such eye movements to be unmasked, is critical to proper diagnosis and ultimate alleviation of the visual impairment these patients experience.