Comparison of methylation episignatures in KMT2B- and KMT2D-related human disorders.

Aim & methods: To investigate peripheral blood methylation episignatures in KMT2B-related dystonia (DYT-KMT2B), the authors undertook genome-wide methylation profiling of ∼2 M CpGs using a next-generation sequencing-based assay and compared the findings with those in controls and patients with KMT2D-related Kabuki syndrome type 1 (KS1). Results: A total of 1812 significantly differentially methylated CpG positions (false discovery rate < 0.05) were detected in DYT-KMT2B samples compared with controls. Multi-dimensional scaling analysis showed that the 10 DYT-KMT2B samples clustered together and separately from 29 controls and 10 with pathogenic variants in KMT2D. The authors found that most differentially methylated CpG positions were specific to one disorder and that all (DYT-KMT2B) and most (Kabuki syndrome type 1) methylation alterations in CpG islands were gain of methylation events. Conclusion: Using sensitive methylation profiling methodology, the authors replicated recent reports of a methylation episignature for DYT-KMT2B. These findings will facilitate the development of episignature-based assays to improve diagnostic accuracy.

The authors compared the DNA methylation patterns in blood from individuals with two rare neurodevelopmental disorders (childhood-onset dystonia [DYT-KMT2B] and Kabuki syndrome type 1) and healthy control samples. These two disorders are associated with pathogenic variants in KMT2B and KMT2D, which encode proteins with related functions but cause distinct inherited disorders. Comparison of the methylation patterns in the two disorders showed that most DNA regions with altered methylation patterns differed between the two disorders and controls. These findings suggest that analyzing DNA methylation patterns could improve diagnostic testing for these disorders and might provide insights into how the clinical features of these disorders are caused.

Effects of Peripheral Vertigo on Inflammatory and Immunologic Laboratory Markers.

The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV) are markers of subclinical inflammation and atherothrombosis. We investigated whether these easily accessible blood count parameters are affected by peripheral vertigo (PV). We studied 142 patients who were diagnosed with PV and referred to our hospital along with 135 healthy patients who were free of inflammation as a control group. The patient group was divided into 3 study groups depending on the presence of benign paroxysmal positional vertigo (BPPV): BPPV, vestibular dysfunction (VD), and BPPV + VD. The total patient group and 3 subgroups were compared to the control group with respect to the NLR, PLR, and MPV. The NLR and PLR were calculated by dividing the neutrophil and platelet values by the lymphocyte value. Of 142 patients, 43, 71, and 28 patients comprised the BPPV, VD, and BPPV + VD groups, respectively. There was no statistically significant difference (P > .05) in the NLR, PLR, or MPV between the main patient group or the individual patient subgroups and the control group. Our findings suggest that NLR, PLR, and MPV do not change significantly either in BPPV or in other peripheral vestibular disorders.

High-sensitivity C-reactive protein as an indicator of ischemic stroke in patients with isolated acute vestibular syndrome: Retrospective observational study.

Ischemic strokes presenting with isolated acute vestibular syndrome (AVS) are not rare and still are challenging for diagnosis. In this retrospective study, we aimed to investigate the association of high-sensitivity C-reactive protein (hs-CRP) with stroke in patients with isolated AVS. A total of 217 patients with isolated AVS within 3 days of symptom onset were included. Serum hs-CRP levels were assessed within 24 hours of admission. The relationship between hs-CRP levels and stroke in patients with AVS were analyzed using univariate and multivariate models. The results showed that hs-CRP levels were significantly higher in infarction patients than that in noninfarction group. The stroke occurrence was increased with increasing quartile levels of hs-CRP. The highest quartile level of hs-CRP was associated with a higher occurrence of stroke compared with the lowest quartile group (adjusted odds ratio [OR], 4.099; 95% confidence interval [CI], 1.272-13.216; P = .018). We also found that male gender (adjusted OR, 5.635; 95% CI, 2.212-14.352; P < .001) and increased low-density lipoprotein cholesterol (LDL-C) (adjusted OR, 2.543; 95% CI, 1.175-5.505; P = .018) were independently associated with stroke in patients with AVS. In addition, using the receiver operating characteristic curve analysis, our study yielded a threshold value of hs-CRP at 1.82 mg/L, and demonstrated that combining hs-CRP with LDL-C improved the discriminatory ability to identify stroke patients with AVS (area under the curve of the combined model: 0.753; 95% CI = 0.684-0.821; P < .001). Hs-CRP may be a useful indicator of stroke in patients with AVS. More attention should be paid to the patients with elevated hs-CRP level.

Acute vestibular syndrome associated with anti-GQ1b antibody.

OBJECTIVES: To delineate the clinical features and ocular motor findings in acute vestibular syndrome (AVS) associated with anti-GQ1b antibodies. METHODS: We reviewed 90 patients with positive serum anti-GQ1b antibody in association with various neurological syndromes at Seoul National University Bundang Hospital from 2004 to 2018. The diagnoses included typical Miller Fisher syndrome (n = 31), acute ophthalmoplegia without ataxia (n = 27), Guillain-Barre syndrome with ophthalmoplegia (n = 18), AVS (n = 11), and Bickerstaff brainstem encephalitis (n = 3). Of them, the 11 patients with AVS formed the basis of this study. We also conducted a systematic review on AVS reported in association with anti-GQ1b antibody. RESULTS: Patients with AVS showed various ocular motor findings that included head-shaking nystagmus (n = 6), spontaneous nystagmus (n = 5), gaze-evoked nystagmus (n = 5), central positional nystagmus (n = 3), canal paresis (n = 2), and abnormal head-impulse tests (n = 1) without any internal or external ophthalmoplegia. Compared to those with other subtypes, patients with AVS mostly showed normal deep tendon reflexes (8 of 11 [73%], p = 0.002) and normal results on nerve conduction studies (4 of 4 [100%], p = 0.010). The clinical and laboratory findings resolved or improved markedly in all patients within 6 months of symptom onset. Systematic review further identified 7 patients with AVS and positive serum anti-GQ1b antibody who showed various ocular motor findings, including gaze-evoked nystagmus, saccadic dysmetria, central positional nystagmus, and ocular flutter or opsoclonus. CONCLUSION: Anti-GQ1b antibody may cause acute vestibulopathy by involving either the central or peripheral vestibular structures. AVS may constitute a subtype of anti-GQ1b antibody syndrome.

Age-related deterioration of saccule-related neural function is associated with decreased estimated glomerular filtration rate and increased free thyroxine.

OBJECTIVE: This study attempted to identify systemic factors for age-related decline in neural function originating from the saccule using cervical vestibular-evoked myogenic potentials (cVEMP) parameters. METHODS: We recruited 129 symptomatic vertiginous patients who did not have known disorder affecting the cVEMP pathway (mean age = 52.4 ±â€¯13.9). The indicators of saccule-related neural function were the sum of normalized cVEMP amplitude (SNA) and the average of p13 latency on both sides (average latency, AL). Any associations between cVEMP and systemic factors were evaluated using a linear regression. RESULT: SNA decreased with ageing (p < 0.001) in univariable regression. The estimated glomerular filtration rate (eGFR) was positively associated with SNA (p = 0.002). Hematocrit, C-reactive protein, vitamin D, and free thyroxine (T4) showed a trend of association with SNA (p < 0.2). SNA was associated with ageing, increased free T4, and decreased eGFR in multivariable analysis. In the subgroup analysis, SNA was significantly associated with free T4 in younger patients (mean age = 41.5 ±â€¯9.91) but not in the older ones (mean age = 63.5 ±â€¯6.54). AL did not show any significant associations with systemic factors. CONCLUSION: Decreased eGFR and increased free T4 as well as aging may be risk factors for decline of saccule-related neural function. SIGNIFICANCE: Neural function originating from the saccule may be affected by systemic factors.

Hyperinsulinemic hypoglycemia in Beckwith-Wiedemann, Sotos, and Kabuki syndromes: A nationwide survey in Japan.

Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth syndrome that is occasionally associated with hyperinsulinemic hypoglycemia (HH) in the neonatal period. Sotos syndrome (SS) and Kabuki syndrome (KS) are other malformation syndromes that may be complicated with HH, however, the detailed clinical characteristics of HH accompanied with these syndromes remain unclear. We herein conducted a nationwide questionnaire survey in Japan. We sent a primary questionnaire concerning the clinical experience for these syndromes to 347 perinatal care institutions. As a result, 222 departments or hospitals returned the questionnaires and the total numbers of BWS, SS, and KS patients were 113, 88, and 51, respectively. We sent a secondary questionnaire to 31 institutions where patients with these syndromes presented with HH during infancy. The secondary questionnaires were returned from the institutions and the numbers of patients were 16 for BWS, 9 for SS, and 3 for KS, respectively. Then, we compared the clinical characteristics of infants suffering from transient HH with and without these dysmorphic syndromes. As a result, BWS, SS, and KS patients showed significantly larger body size, lower Apgar scores, higher insulin levels at HH, and shorter durations of HH than non-dysmorphic infants with transient HH. We propose that a careful observation for the signs of HH, even if not specific to the syndromes, is important for the diagnosis of patients with BWS, SS, and KS in the postnatal period. © 2016 Wiley Periodicals, Inc.

Growth Hormone Stimulation Tests in Children with Kabuki Syndrome.

BACKGROUND/AIMS: Kabuki syndrome is a multiple congenital malformation syndrome with a variety of clinical features including short stature. The cause of this postnatal short stature remains unknown. METHODS: Eighteen children with genetically proven Kabuki syndrome (8 boys and 10 girls; ages 3.3-9.9 years, with a mean of 6.7 years) who underwent growth hormone (GH) stimulation tests were evaluated in a prospective study. Two GH stimulation tests were conducted, including insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3) serum levels. GH stimulation peaks in relation to age, sex, height, body mass index (BMI), IGF-I, and IGFBP-3 SD scores (SDS) were analyzed. RESULTS: Five of the 18 children (27.8%) were biochemically GH deficient. This was not correlated with BMI SDS. Of all patients, only 1 had an IGF-I below -2 SD and did not fulfill the GH deficiency criteria. The mean IGF-I level was below normal (-0.8 SD). All subjects had normal IGFBP-3 levels. CONCLUSIONS: The utility of performing GH stimulation tests on Kabuki syndrome children as an indication of GH status in short stature is questionable. IGF-I levels did correlate neither with the GH stimulation peak nor consequently with the diagnosis of GH deficiency.

Vestibular function disorders and potential mechanisms in irradiation nasopharyngeal carcinoma patients.

CONCLUSIONS: Vestibular function disorders were widespread among nasopharyngeal carcinoma (NPC) patients. The radiation doses to the inner ears were associated with the incidence of vestibular function disorders, but the correlations were mild. The inflammatory responses and possible resolution obstacles of inflammation participated in persistent vestibular function disorders after irradiation. OBJECTIVES: To investigate the incidence of vestibular function disorders in NPC patients after irradiation and potential mechanisms. METHODS: Patients who received radical intensity-modulated radiotherapy for their NPC were recruited. The serum levels of IL-6 and IL-17 were detected by ELISA method. Vestibular evoked myogenic potential (VEMP) tests were used to evaluate vestibular function and correlation analyses were used to analyze the potential mechanisms of vestibular function disorders. RESULTS: Thirty-eight patients were included. The incidences of abnormal ocular VEMP (oVEMP) and cervical VEMP (cVEMP) were 65.79% and 80.26% at the time of completion of radiotherapy, and 61.84% and 71.05% at 3 months after radiotherapy. The mean and maximum radiation doses to the inner ears were both significantly associated with abnormal oVEMP and cVEMP (p < 0.05, all), but the correlations were all mild. The serum levels of IL-6 and IL-17 were both significantly associated with abnormal oVEMP and cVEMP after irradiation (p < 0.05, all).

Concurrent idiopathic vestibular syndrome and facial nerve paralysis in a cat.

CASE REPORT: A 4-year-old male neutered Domestic Medium-hair cat was referred for right head tilt and ataxia of 2 weeks duration. On examination it was determined that the cat had right facial nerve paralysis and peripheral vestibular signs. Haematology and serum biochemical testing were performed in addition to magnetic resonance imaging of the brain and ears, and cerebrospinal fluid analysis. An underlying condition was not identified. A diagnosis of idiopathic vestibular syndrome and concurrent idiopathic right facial nerve paralysis was consequently made. The cat was re-evaluated over the following weeks and was determined to have complete resolution of clinical signs within 7 weeks. CONCLUSION: Vestibular dysfunction and concurrent facial nerve paralysis have previously been reported in the cat, but not of an idiopathic nature.

[The level of beta-endorphin, chronic stress, and depression associated with vestibular pathology].

The objective of the present study was to evaluate the presence and the severity of manifestations of anxiety and depression in the patients presenting with vestibular dysfunction making use of the psychometric scales and taking into consideration variations in the plasma beta-endorphin level as a biochemical marker before and after medicamental and physical rehabilitative treatment. A total of 8 patients presenting with stage I-III Meniere's disease and 8 patients suffering from dyscirculatory encephalopathy concomitant with vestibular ataxic syndrome were available for the observation. We separately analysed the results of examination of two patients with vestibular neuronitis and two others presenting with vestibular migraine. It was shown that the degree of anxiety and depression correlated with the plasma beta-endorphin level whereas its correlation with the severity of vestibular oculomotor and vestibular motor disorders during the inter-bout periods was not documented. It was demonstrated that the plasma beta-endorphin level was many times higher than the normal value of 20 ng/l in the patients with the well apparent vegetative symptoms accompanied by dizziness and the patients suffering from vegetative migraine.

Clinical and molecular spectrum of renal malformations in Kabuki syndrome.

OBJECTIVE: To determine the frequency and types of renal malformations, and to evaluate renal function in a cohort of patients with Kabuki syndrome (KS). STUDY DESIGN: Renal ultrasound scans and plasma creatinine measurements were collected from a French cohort of 94 patients with genotyped KS. Renal function was evaluated based on the estimated glomerular filtration rate. A genotype-phenotype study was conducted for renal and urinary tract malformations. RESULTS: Renal malformations were present in 22% of cases, and urinary tract anomalies were present in 15%. Renal malformations were observed in 28% of the MLL2 mutation-positive group and in 0% of the MLL2 mutation-negative group (P = .015). No correlation was found between the presence or absence of renal or urinary tract malformations and the location or type of MLL2 mutation. Renal function was normal except for 1 patient with a MLL2 mutation diagnosed in the first days of life and severe renal disease due to unilateral renal agenesia and controlateral severe hypoplasia that progressed to the terminal stage at age 2 years. CONCLUSION: Our study emphasizes the need for ultrasound and renal function screening in children diagnosed with KS.

The relationship of homocysteine, vitamin B12, folic acid levels with vertigo.

OBJECTIVES: In this study the relationship of serum homocysteine, vitamin B12, folic acid levels and peripheral vestibular dysfunction (PVD) was investigated. PATIENTS AND METHODS: Forty-one patients (31 females, 10 males; mean age 57.34±14.3 years; range 12 to 80 years) who admitted to Baskent University Hospital Ear Nose and Throat Department between the dates of April 2005 - December 2007 with complaint of vertigo were prospectively analyzed and diagnosed using audio-vestibular test, at the same time serum homocysteine, vitamin B12, folic acid measurements was done from the blood samples of patients. The patients were divided into three groups as Meniere's disease, vestibular neurinitis, and benign paroxismal positional vertigo (BPPV) according to the diagnoses and serum homocysteine, vitamin B12, folic acid levels of patients were compared to normal values in and between groups. RESULTS: Of the patients, 29.3% (n=12) were diagnosed with Meniere's disease, 36.6% (n=15) with vestibular neurinitis, and 34.1% (n=14) with BPPV. Serum homocysteine leves of patients were 12.42±3.56 umol/L, 11.32±4.14 umol/L and 10.72±2.95 umol/L (p>0.05) in Meniere's disease, vestibular neurinitis, and BPPV respectively; vitamin B12 levels were 371.58±141.35 pg/ml, 288.13±139.51 pg/ml, 352.14±150.41 pg/ml (p>0.05) respectively and folic acid levels were 8.76±3.2 umol/L, 10.63±6.59 umol/L, 8.8±3.18 umol/L (p>0.05) respectively. The values were similar in all patients. No statistically significant difference was found in and between groups comparing with normal values. CONCLUSION: This is the first prospective study investigating the relationship of serum homocystein, vitamin B12 and folic acid levels with PVD. We found that there is no relationship of homocysteine, vitamin B12, folic acid levels with PVD.

Blood glucose and insulin levels in patients with peripheral vestibular disease.

UNLABELLED: Metabolic disorders can cause dizziness. AIM: to study the prevalence of glucose and glucose-insulin alterations in patients with peripheral vestibular disorders by studying the four-hour glucose-insulin curve; to check at what time there was the highest prevalence of altered cases and whether the glucose and insulin curves together are better than the isolate glucose curve and fasting glucose curve. MATERIALS AND METHODS: retrospective study, analyzing 81 four-hour glucose-insulin curves in patients with peripheral vestibular dizziness. RESULTS: Four-hour glucose-insulin curve alterations happened in 87.7% of the patients. Hypoglycemia was seen in 61.7% of the cases, hyperinsulinemia in 55.5%, hyperglycemia in 27.2%, glucose intolerance in 12.3% and hypoinsulinemia in 1.2%. Normal tests were seen in 12.3 % of the cases and altered fasting glucose in 23.5%. CONCLUSIONS: The four-hour glucose-insulin curve analysis showed that 87.7% of the patients with dizziness and suspicion of peripheral vestibular disorder had glucose or insulin metabolism disorders. The highest number of alterations was seen up to the third and fourth hour of the glucose-insulin curve. The glucose and insulin curves together overcame the glucose curve alone and fasting glucose curve in regards of the prevalence of altered cases.

Blood glucose and insulin levels in patients with peripheral vestibular disease / Avaliação da curva glicoinsulinêmica nos pacientes com vestibulopatia periférica

Metabolic disorders can cause dizziness. AIM: to study the prevalence of glucose and glucose-insulin alterations in patients with peripheral vestibular disorders by studying the four-hour glucose-insulin curve; to check at what time there was the highest prevalence of altered cases and whether the glucose and insulin curves together are better than the isolate glucose curve and fasting glucose curve. MATERIALS AND METHODS: retrospective study, analyzing 81 four-hour glucose-insulin curves in patients with peripheral vestibular dizziness. RESULTS: Four-hour glucose-insulin curve alterations happened in 87.7 percent of the patients. Hypoglycemia was seen in 61.7 percent of the cases, hyperinsulinemia in 55.5 percent, hyperglycemia in 27.2 percent, glucose intolerance in 12.3 percent and hypoinsulinemia in 1.2 percent. Normal tests were seen in 12.3 percent of the cases and altered fasting glucose in 23.5 percent. CONCLUSIONS: The four-hour glucose-insulin curve analysis showed that 87.7 percent of the patients with dizziness and suspicion of peripheral vestibular disorder had glucose or insulin metabolism disorders. The highest number of alterations was seen up to the third and fourth hour of the glucose-insulin curve. The glucose and insulin curves together overcame the glucose curve alone and fasting glucose curve in regards of the prevalence of altered cases.

Alterações metabólicas podem causar tontura. OBJETIVOS: Identificar a prevalência das alterações glicêmicas e glicoinsulinêmicas em pacientes com vestibulopatia periférica por meio da curva glicoinsulinêmica de 4 horas; verificar em que momento do exame foi encontrada a maior prevalência de casos alterados e se as curvas glicêmica e insulinêmica em conjunto superam a curva glicêmica isolada e glicemia de jejum. MATERIAL E MÉTODO: Estudo retrospectivo, com análise de 81 curvas glicoinsulinêmicas de quatro horas em pacientes com queixa de tontura de origem vestibular periférica. RESULTADOS: Alterações na curva glicoinsulinêmica de 4 horas ocorreram em 87,7 por cento dos pacientes. Hipoglicemia ocorreu em 61,7 por cento dos casos, hiperinsulinemia em 55,5 por cento, hiperglicemia em 27,2 por cento, intolerância à glicose em 12,3 por cento e hipoinsulinemia em 1,2 por cento. Exame normal em 12,3 por cento dos casos e glicemia de jejum alterada em 23,5 por cento. CONCLUSÕES: A análise da curva glicoinsulinêmica de 4 horas evidenciou que 87,7 por cento dos pacientes com tontura e hipótese de disfunção vestibular periférica apresentaram alterações do metabolismo da glicose ou insulina. O maior número de alterações foi encontrado até a terceira e quarta horas da curva glicoinsulinêmica. As curvas glicêmicas e insulinêmicas em conjunto superaram a curva glicêmica isolada e glicemia de jejum quanto à prevalência de casos alterados.

Changes in blood serotonin in patients with tinnitus and other vestibular disturbances.

The role of serotonin as a mediator and stress hormone and its function in vessel tonus regulation is proved. The aim of the work is to study the concentration of serotonin in blood in patients with vestibular disturbances before and after vestibular provocation and in patients with tinnitus. The study was performed on 134 persons distributed among three groups: group I, 35 patients with vestibular disturbances; group II, 75 healthy persons; group III, 24 patients with tinnitus. Serotonin was examined twice in patients with vestibular disturbances (group I) and in healthy persons (group II), before and 15 minutes after vestibular provocation realized by a cold caloric test, and once in patients with tinnitus (group III). Vestibular loading provokes changes in blood serotonin: In vestibularly stable persons, serotonin decreases and comparatively weaker vestibular vegetative reactions develop. The role of serotonin in the compensatory mechanisms of the organism related to vestibular crisis is discussed. We recommend its inclusion with routine neurootological examinations for selecting candidates for work in conditions that overload the vestibular analyzer. Patients with tinnitus have serotonin blood values that significantly exceed the referent ones.

Serum antibodies against membranous labyrinth in patients with "idiopathic" bilateral vestibulopathy.

To investigate the possibility of an autoimmune mechanism in idiopathic bilateral vestibulopathy (IBV), we screened patients' sera for antibodies against inner ear structures. IgG antibodies against membranous labyrinth (ampulla, semicircular canals, saccule and utricle) were detected in 8 of 12 patients by immunofluorescence on rat inner ear cryosections. All but one serum of 22 healthy controls and the sera of 6 patients with known autoimmune disorders showed only background staining. Low-titre anti-nuclear IgM antibodies were present in three control sera and one IBV serum. High-titre anti-nuclear IgM was found in a patient with lupus erythematosus and in one with scleroderma. Anti-nuclear IgM was not organ-specific. No human serum used contained detectable anti-vascular preformed antibodies. Cross-reactivity to sections of liver, kidney, cornea, brain and skeletal muscle was absent. Double-staining for IgG and F-actin, the primary constituent of hair cell cilia, did not show predominant Ig-coating of sensory hair cells. Immunosuppressive therapy in 3 IBV patients did not improve the disorder, probably owing to irreversible loss of sensory and neural structures. These data suggest that the bulk of anti-labyrinthine autoantibodies may be an epiphenomenon, yet a small subgroup of organ-specific autoantibodies may synergize with a cellular response in the development of vestibular lesions.

Antibodies to glycosphingolipid antigens in patients with immune-mediated cochleovestibular disorders.

HYPOTHESIS: To determine the presence of antibodies against the glycosphingolipid antigen sulfated glucuronic lactosominyl paragloboside (SGLPG) in the sera of patients suspected of immune-mediated cochleovestibular disorders (IMCVD). BACKGROUND: Glycospingolipids are molecules present on the surface of normal nerve cells and are considered antigenic. Previous studies have isolated these antigens in vestibular neuroepithelia, cochleovestibular nerves and endolymphatic sacs. METHODS: The sera of 22 patients suspected of IMCVD were tested for antibodies against the antigen SGLPG. Thin-layer chromatography-immunostaining method was used. RESULTS: Antibody titers were elevated in 63.6% of patients tested. Statistical significance (p < 0.0001) was achieved since reactivity was seen in only 7% of 43 age-matched healthy controls. CONCLUSIONS: Antibodies to SGLPG antigens are present in some patients with IMCVD. Because SGLPD antigens have been previously isolated in the inner ear and the cochleovestibular nerve, these structures can potentially become targets for anti-SGLPG antibodies.

[Impaired vestibular diagnosis by the effect of alcohol]. / Behinderung vestibulärer Diagnostik durch Alkoholeinfluss.

BACKGROUND: The aim of our study was to estimate the qualitative and quantitative influence of different blood alcohol concentrations on the results of vestibular testing. METHODS: We investigated the influence of ethanol on the results of well established neurootologic tests in 40 persons with blood alcohol concentrations of 0.0%, 0.4%, and 0.8%. RESULTS: The intensity of the vestibuloocular reflex during sinusoidal rotation was not influenced by ethanol. The directional preponderance of the nystagmic responses to the left was enlarged from 5.8% (0.0/1000) to 13.4% (0.4/1000) and to 15.5% (0.8/1000). The capability of suppressing the vestibuloocular reflex by visual fixation was reduced to 70% (0.4/1000) and, respectively, 46% (0.8/1000) of the 0.0/1000 result. The maximum speed of smooth pursuit was diminished to 84.1% (0.4/1000) and, respectively, 65.3% (0.8/1000) of the 0.0/1000 values. The pursuit movements resembled those of patients with central vestibular lesions. The latency of saccades increased from 200 ms (0.0/1000) to 220 ms (0.4 and 0.8/1000); the velocity was not changed by ethanol. At maximum target speed the gain of optokinetic nystagmus was reduced at 0.4/1000 to 66.3% and at 0.8/1000 to 51.7%, with different results to the right and the left side. CONCLUSIONS: Our results show that even slight amounts of ethanol can simulate symptoms of vestibular diseases, resulting in false diagnoses and errors in determining the therapeutic strategy.