GAA-FGF14 disease: defining its frequency, molecular basis, and 4-aminopyridine response in a large downbeat nystagmus cohort.

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.

12†The incidence, clinical features, and management of essential infantile esotropia in the United Kingdom. A British Ophthalmology Surveillance Unit (BOSU) study - Final Report.

Studies from the UK have reported declining rates of surgery for childhood esotropia. It is not known if this equates to a reduced incidence of essential infantile esotropia (EIE). A national study was undertaken through the British ophthalmology surveillance unit (BOSU) to determine the incidence presenting features and management of EIE in the UKData from a prospective national observational cohort of newly diagnosed EIE presenting to clinicians in the United Kingdom over a 12-month period was collected. Cases with a confirmed diagnosis by a clinician of a constant, non-accommodative esotropia ≥ 20 prism dioptres (PD), presenting at ≤ 12months, with no neurological or ocular abnormalities were identified through BOSU. Follow up data was collected at 12 months. Data was collected on the age, gender, ethnicity, birth history, age at diagnosis, age at intervention, angle of esotropia, refraction, associated features of amblyopia, overelevation in adduction (OEIA), latent nystagmus and dissociated vertical deviation (DVD), method of management and outcomes.During the period of observation between October 2017 to October 2018 a total of 57 cases were reported giving an incidence of EIE of 1 in 12,828 live births with a corrected incidence of 1 in 9027 live births allowing for estimated under reporting. The mean age of diagnosis and intervention were 7.05± 2.6 months (range 2 to 12 months) and 14.7± 4.9 (range 6.5-28.1 months) respectively. The majority were Caucasians 86.5% and 52.7% were female. Management was surgical in 59.6%, and botulinum toxin alone in 22.8%, 17.5% were observed. There was no significant difference in the age of presentation (P=0.6), gender (P=0.8), prematurity (P=0.5), deprivation indices (P=0.68), refraction (P=0.7), OEIA (P=0.6), DVD (P=0.7) or follow up (P=0.3) between the three groups. The preoperative angle of esotropia was smaller in the observation group (P=0.04). The post-operative angle of esotropia was not statistically significant between botulinum toxin or surgery (P=0.3) though the age of intervention was earlier in the botulinum group (P=0.007). Early intervention did not influence the motor post intervention outcomes between 0-10 prism dioptres of esotropia (P=0.78). Amblyopia (P=0.02) and latent nystagmus (P=0.009) was more common in the observation group.The incidence of EIE in the UK is considerably lower than reported in other population-based studies. The preferred method of treatment was surgical with earlier intervention in those treated with botulinum toxin. An early age of intervention did not influence motor outcomes. Parental choice and amblyopia treatment were reasons cited for conservative management in the observational group.

The effects of continuous administration of diazepam on the recovery of lesion-induced nystagmus in unilaterally labyrinthectomised rats.

BACKGROUND: Diazepam, a gamma-aminobutyric acid type A receptor agonist, is classified as a vestibular suppressant and is effective in treating acute vertigo. However, its effects on vestibular compensation (VC) remain unclear. OBJECTIVES: We examined the effects of continuous administration of diazepam on the frequency of spontaneous nystagmus (SN) after unilateral labyrinthectomy (UL) as an index of the initial process of VC in rats. MATERIALS AND METHODS: Diazepam was continuously administered at doses of 3.5 and 7.0 mg/kg/day, intraperitoneally, via an osmotic minipump. The frequency of SN beating against the lesion side after UL was measured. Potassium chloride (KCl) solution (1 M) was injected intratympanically to induce SN beating to the injection side. RESULTS: Continuous administration of diazepam significantly and dose-dependently decreased the frequency of SN after UL, and also reduced the x intercept of the nonlinear regression curve of the decline in UL-induced SN with time in rats. However, the continuous administration of diazepam did not affect the frequency of intratympanic KCl-induced SN in the rats. CONCLUSION: These findings suggested that continuous administration of diazepam accelerates the initial process of VC; however, it does not suppress the nystagmus-driving mechanisms in rats.

Centripetal Nystagmus, Slow Saccades, Cerebellar Ataxia, and Parkinsonism in a Patient With Anti-GAD65-Associated Stiff Person Syndrome Spectrum Disorder.

ABSTRACT: A 68-year-old woman with positional dizziness and progressive imbalance presented for vestibular evaluation. Examination was notable for spontaneous downbeat nystagmus (DBN), horizontal and vertical gaze-evoked nystagmus (GEN) with centripetal and rebound nystagmus, and positional apogeotropic nystagmus. There was also mild-moderate slowing of saccades horizontally and vertically and poor fast phases with an optokinetic stimulus. Further consultation by a movement disorder specialist uncovered asymmetric decrementing bradykinesia and rigidity, masked facies, and a wide-based stance without camptocormia. Screening serum laboratory results for metabolic, rheumatologic, infectious, heavy metal, endocrine, or vitamin abnormalities was normal. Surveillance imaging for neoplasms was unremarkable, and cerebrospinal fluid (CSF) analysis was negative for 14-3-3 and real-time quaking-induced conversion (RT-QuIC). However, her anti-glutamic acid decarboxylase-65 (GAD65) immunoglobulin G (IgG) level was markedly elevated in serum to 426,202 IU/mL (reference range 0-5 IU/mL) and in CSF to 18.1 nmol/L (reference range <0.03 nmol/L). No other autoantibodies were identified on the expanded paraneoplastic panel. The patient was referred to neuroimmunology, where torso rigidity, spasticity, and significant paravertebral muscle spasms were noted. Overall, the clinical presentation, examination findings, and extensive workup were consistent with a diagnosis of anti-GAD65-associated stiff person syndrome-plus (musculoskeletal plus cerebellar and/or brainstem involvement). She was subsequently treated with intravenous immunoglobulin (IVIg) and has been stable since commencing this therapy. In patients with centripetal nystagmus, especially in association with other cerebellar findings, an autoimmune cerebellar workup should be considered.

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

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

Pharmacological and Behavioral Strategies to Improve Vision in Acquired Pendular Nystagmus.

BACKGROUND Acquired pendular nystagmus (APN) is a back and forth, oscillatory eye movement in which the 2 oppositely directed slow phases have similar waveforms. APN occurs commonly in multiple sclerosis and causes a disabling oscillopsia that impairs vision. Previous studies have proven that symptomatic therapy with gabapentin or memantine can reduce the nystagmus amplitude or frequency. However, the effect of these medications on visual acuity (VA) is less known and to our knowledge the impact of non-pharmacological strategies such as blinking on VA has not been reported. This is a single observational study without controls (Class IV) and is meant to suggest a future strategy for study of vision in patients with disabling nystagmus and impaired vision. CASE REPORT A 49-year-old woman with primary progressive multiple sclerosis with spastic paraparesis and a history of optic atrophy presented with asymmetrical binocular APN and bothersome oscillopsia. We found that in the eye with greater APN her visual acuity improved by 1 line (from 0.063 to 0.08 decimals) immediately after blinking. During treatment with memantine, her VA without blinking increased by 2 lines, from 0.063 to 0.12, but improved even more (from 0.12 to 0.16) after blinking. In the contralateral eye with a barely visible nystagmus, VA was reduced by 1 line briefly (~500 ms) after blinking. CONCLUSIONS In a patient with APN, blinking transiently improved vision. The combination of pharmacological treatment with memantine and the blinking strategy may induce better VA and less oscillopsia than either alone.

Vértigo, más allá del mareo / Vertigo: beyond dizziness

El vértigo se define como la sensación de inestabilidad con giro de objetos. En pediatría, debido a la dificultad de los pacientes a la hora de expresar sus síntomas (sobre todo en los más pequeños), se debe tener en cuenta el vértigo a la hora de abordar un paciente que consulta por inestabilidad, mareo, vómitos recurrentes o en lactantes con episodios paroxísticos de irritabilidad. El diagnóstico de vértigo es clínico, por lo que realizar una buena anamnesis y una exploración física completa es fundamental. Es importante clasificar el vértigo en periférico o central, dado que conlleva un manejo diferente y, así mismo, para diferenciar entre episodios agudos únicos y agudos recurrentes. Además, siempre que sea posible, la exploración se completará con un examen neurootológico por parte de un especialista en otorrinolaringología (ORL). Se presentan a continuación una serie de casos de vértigo periférico diagnosticados en las urgencias de pediatría y, a raíz de estos, se hace un repaso de las principales características y etiologías del vértigo periférico en pediatría (AU)

Vertigo is defined as a sensation of spinning instability. In paediatric practice, due to the difficulty of patients in expressing their symptoms (especially the younger ones), vertigo must be contemplated in the management of a patient presenting with instability, motion sickness, recurrent vomiting or paroxysmal episodes of irritability in toddlers.The diagnosis of vertigo is clinical, and therefore requires a thorough history-taking and full physical examination. It is important to classify vertigo as peripheral or central, as they are managed differently, as well as differentiating acute from recurrent episodes. In addition, whenever possible, the evaluation should be completed with a neurologic and hearing examination by an ear-nose-throat (ENT) specialist.We present a series of cases of peripheral vertigo diagnosed in the emergency department, based on which we review the main characteristics and aetiologies of peripheral vertigo in the paediatric population. (AU)

Analysis of the nystagmus characteristics of cupula diseases: A case report.

INTRODUCTION: Clinically, there is a kind of patients with positional vertigo or dizziness, which occurs when they turn left or right, look down or up, lie down or sit up. With a long duration and varying frequency, it is not consistent with the manifestations of benign paroxysmal positional vertigo (BPPV). In addition, the persistent geotropic direction-changing positional nystagmus (PG-DCPN) was observed in a supine head-roll test. PATIENT CONCERNS: With no apparent trigger for visual rotation and a sense of self instability, an 81-year-old female patient had suffered from vertigo for 3 days. The vertigo occurred every day, lasting several minutes each time, and associated with head movements and changes in body position. In a supine head-roll test, it appeared persistent geotropic direction-changing positional nystagmus for a long time, without latency, fatigability and in the presence of 3 zero planes. DIAGNOSIS: Light cupula. INTERVENTIONS: Difenidol hydrochloride 25 mg orally 3 times/day for 2 weeks and betahistine hydrochloride 12 mg orally 3 times/day for 1 month were administered. OUTCOMES: After 1 month of treatment, the patient's vertigo symptoms disappeared. And in the supine head-roll test, the persistent geotropic direction-changing positional nystagmus disappeared. CONCLUSION: We report the characteristics of nystagmus produced in a typical patient with light cupula during the supine head-roll test. After reviewing the relevant literatures, we believe that a simpler method can be used to identify canalolithiasis and cupula disease, to distinguish light and heavy cupula, and to determine the pathological semicircular canal to which the lesion belongs.

Pharmacotherapy of cerebellar and vestibular disorders.

PURPOSE OF REVIEW: Major therapeutic advances have been made in patients with episodic and progressive cerebellar ataxias, downbeat nystagmus and some vestibular disorders. We provide an update review on this subject highlighting important research findings from the last two years. RECENT FINDINGS: Recently, the use of omaveloxolone for 2 years significantly improved upright stability in Friedreich's ataxia patients. In an open-label study, N-acetyl-l-leucine administered for 6-weeks significantly improved clinical impression of change, ataxia, and quality of life in patients with Niemann-Pick disease type C1. A 12-week treatment with dalfampridine was associated with improved standing balance in a subgroup of patients with multiple sclerosis. A gluten-free diet alone improved ataxia in half of patients with antiglutamic acid decarboxylase (GAD) ataxia, suggesting that gluten sensitivity might be part of the underlying pathogenesis in anti-GAD ataxia. In a head-to-head trial, both prolonged-release 4-aminopyridine (4-AP) and acetazolamide effectively reduced the attacks up to 60% in patients with episodic ataxia type 2 (EA2), albeit 4-AP had fewer adverse effects. Small observational studies have shown that patients with episodic vestibular syndrome who cannot be diagnosed as definite or probable vestibular migraine, might still improve vestibular symptoms following preventive treatment for migraine. The use of vitamin D supplementation in benign paroxysmal positional vertigo, steroids in acute unilateral vestibulopathy, and betahistine in Ménière's disease patients remains controversial. SUMMARY: Although the use of several therapies is being established in the treatment of cerebellar and vestibular disorders, there is an urgent need for prospective controlled therapeutic trials.

Effects of Acetyl-DL-Leucine on Ataxia and Downbeat-Nystagmus in Six Patients With Ataxia Telangiectasia.

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).

Gabapentin Relieves Vertigo of Periodic Vestibulocerebellar Ataxia: 3 Cases and Possible Mechanism.

OBJECTIVE: The aim of this study was to report relief of optokinetic-triggered vertigo (OKTV) with low-dose gabapentin in three patients with periodic vestibulocerebellar ataxia [episodic ataxia type 4 (EA4); OMIM 606552]. METHODS: Clinical observations and analysis of video-recorded eye movements were used before and after gabapentin. RESULTS: Gabapentin relieved vertigo of all three treated patients with EA4, particularly during activities that typically would induce vertiginous symptoms. Two patients reported 8-12 hours of sustained relief after the first 100 mg dose. One has benefited from 100-200 mg TID for 7 years. Video analysis of nystagmus revealed improved target tracking on smooth pursuit and a steadier gaze hold. CONCLUSIONS: Gabapentin effectively relieved the optokinetic-triggered vertigo in our patients with EA4. Mechanisms are postulated in terms of known tight gabapentin binding to the Purkinje cell voltage-gated calcium channel. The observations may offer insight into this rare disease's neuropathology. © 2021 International Parkinson and Movement Disorder Society.

Topical lambda-cyhalothrin in reducing eye oscillations in a canine model of infantile nystagmus syndrome.

PURPOSE: To determine the ocular and systemic safety of using topical Lambda-Cyhalothrin (LCL) in a canine model of infantile nystagmus syndrome (INS). The rationale for this proposal is based on a case study of a patient whose INS improved after inadvertent ocular exposure to a pyrethroid pesticide containing LCL. METHODS: After in-vitro safety testing and IUCAC approval, we studied increasing concentrations of topical LCL drops (0.002% to 0.07%) in canines with a purposely bred defect in the RPE65 gene resulting in both retinal degeneration and INS. We collected data on ocular and systemic effects and performed eye-movement recordings (EMR). RESULTS: At the 0.07% concentration dose of LCL, there was minimal, reversible, conjunctival hyperemia. There was no other ocular or systemic toxicity. At the 0.06% dose, there was a visible decrease in the INS and EMR showed a 153%-240% increase in the nystagmus acuity function and a 30%-70% decrease in amplitude across gaze. There was also a 40%-60% decrease in intraocular pressure while on the drop in both eyes. CONCLUSION: This animal study suggests this new pharmacological agent has potential for topical treatment of both INS and diseases with raised intraocular pressure. Further, this new treatment approach confirms the importance of extraocular muscle proprioception in ocular motor diseases and their treatment.

Vision loss, gaze palsy, and nystagmus in a patient with leukemia.

A 22-year old male with a history of B-cell acute lymphoblastic leukemia with recent bone marrow transplantation and on immunosuppressive therapy presented with painless, subacute vision loss of two weeks duration. He exhibited a horizontal gaze palsy, nystagmus, and mildly swollen and hyperemic optic discs with peripapillary flame hemorrhage on retinal exam. He had bilateral cecocentral scotomas on visual field exam, and MRI of his brain/orbits demonstrated hyperintensities in the hypothalamus, periaqueductal gray, and dorsal rostral medullary regions. After continued progression of symptoms despite discontinuation of the patient's tacrolimus, an empiric trial of IV thiamine treatment was started before the patient's lab vitamin levels were available, given strong clinical suspicion for a nutritional etiology. The patient's clinical presentation improved dramatically, and he achieved a final visual acuity of 20/20, full visual fields bilaterally, and resolution of nystagmus. A final diagnosis of Wernicke's encephalopathy was supported by his clinical course, imaging findings, and further confirmation with blood thiamine levels. This case presents unique ocular manifestations of Wernicke's encephalopathy and highlights the importance of early diagnosis in this potentially reversible condition.

Experiencia de uso de fampridina en pacientes con nistagmo vertical inferior / Clinical use of 4-aminopyridine in patients with downbeat nystagmus

OBJETIVO: Presentar los resultados del tratamiento con fampridina de liberación prolongada (4-AP-SR) en pacientes con nistagmo vertical inferior. MATERIAL Y MÉTODO: Serie de casos de nistagmo vertical inferior tratados con 10 mg de 4-AP-SR cada 12h. Se valoraron la mejoría clínica y la variación del nistagmo antes y después del tratamiento, registrando la puntuación en el Dizziness Handicap Inventory, la velocidad de la fase lenta del nistagmo y su frecuencia. RESULTADOS: Se trataron 3 pacientes, ninguno de los cuales notó cambios durante el tratamiento en relación con los síntomas visuales, aunque 2 pacientes notaron mejoría subjetiva de la marcha. No se detectaron diferencias significativas en la puntuación del Dizziness Handicap Inventory ni en las variables videonistagmográficas estudiadas. CONCLUSIÓN: No se han detectado cambios en los síntomas visuales con el tratamiento con 4-AP-SR. La contradicción con estudios previos puede estar producida por un bajo tamaño muestral, la etiología de los casos o la forma de medir los resultado

OBJECTIVE: To present the results of treatment with sustained-release fampridine (4-AP-SR) in patients with downbeat nystagmus. MATERIAL AND METHOD: Series of cases with downbeat nystagmus treated with 10 milligrams of 4-AP-SR every 12 hours. The clinical improvement and the variation of the nystagmus before and after the treatment were evaluated, recording the score in the Dizziness Handicap Inventory, the velocity of the slow phase of the nystagmus and its frequency. RESULTS: Three patients were treated, none of whom reported significant subjective changes during the treatment. No significant differences were detected in the Dizziness Handicap Inventory score or in the studied videonystagmographic variables. CONCLUSION: This communication does not present positive results on the use of 4-AP-SR. The contradiction with previous studies may be caused by a small sample size, by the etiology of the cases or by the way in which the results were measured

Gabapentin and Memantine for Treatment of Acquired Pendular Nystagmus: Effects on Visual Outcomes.

BACKGROUND: The most common causes of acquired pendular nystagmus (APN) are multiple sclerosis (MS) and oculopalatal tremor (OPT), both of which result in poor visual quality of life. The objective of our study was to evaluate the effects of memantine and gabapentin treatments on visual function. We also sought to correlate visual outcomes with ocular motor measures and to describe the side effects of our treatments. METHODS: This study was single-center cross-over trial. A total of 16 patients with chronic pendular nystagmus, 10 with MS and 6 with OPT were enrolled. Visual acuity (in logarithm of the minimum angle of resolution [LogMAR]), oscillopsia amplitude and direction, eye movement recordings, and visual function questionnaires (25-Item National Eye Institute Visual Functioning Questionnaire [NEI-VFQ-25]) were performed before and during the treatments (gabapentin: 300 mg 4 times a day and memantine: 10 mg 4 times a day). RESULTS: A total of 29 eyes with nystagmus were evaluated. Median near monocular visual acuity improved in both treatment arms, by 0.18 LogMAR on memantine and 0.12 LogMAR on gabapentin. Distance oscillopsia improved on memantine and on gabapentin. Median near oscillopsia did not significantly change on memantine or gabapentin. Significant improvement in ocular motor parameters was observed on both treatments. Because of side effects, 18.8% of patients discontinued memantine treatment-one of them for a serious adverse event. Only 6.7% of patients discontinued gabapentin. Baseline near oscillopsia was greater among those with higher nystagmus amplitude and velocity. CONCLUSIONS: This study demonstrated that both memantine and gabapentin reduce APN, improving functional visual outcomes. Gabapentin showed a better tolerability, suggesting that this agent should be used as a first-line agent for APN. Data from our investigation emphasize the importance of visual functional outcome evaluations in clinical trials for APN.

Clinical use of 4-aminopyridine in patients with downbeat nystagmus. / Experiencia de uso de fampridina en pacientes con nistagmo vertical inferior.

OBJECTIVE: To present the results of treatment with sustained-release fampridine (4-AP-SR) in patients with downbeat nystagmus. MATERIAL AND METHOD: Series of cases with downbeat nystagmus treated with 10 milligrams of 4-AP-SR every 12hours. The clinical improvement and the variation of the nystagmus before and after the treatment were evaluated, recording the score in the Dizziness Handicap Inventory, the velocity of the slow phase of the nystagmus and its frequency. RESULTS: Three patients were treated, none of whom reported significant subjective changes during the treatment. No significant differences were detected in the Dizziness Handicap Inventory score or in the studied videonystagmographic variables. CONCLUSION: This communication does not present positive results on the use of 4-AP-SR. The contradiction with previous studies may be caused by a small sample size, by the etiology of the cases or by the way in which the results were measured.