Causative factors, epidemiology, and follow-up of bilateral vestibulopathy.

Bilateral vestibulopathy (BV) is characterized by impaired or lost function of both peripheral labyrinths or of the eighth nerves. In a review of 255 patients (mean age +/- SD, 62 +/- 16 years) with BV diagnosed in the authors' dizziness unit between 1988 and 2005, 62% of the patients were male. Previous vertigo attacks had occurred in 36%, indicating a sequential manifestation. The definite cause of BV was determined in 24% and the probable cause in 25%. The most common causes were ototoxic aminoglycosides (13%), Ménière's disease (7%), and meningitis (5%). Strikingly, 25% exhibited cerebellar signs. Cerebellar dysfunction was associated with peripheral polyneuropathy in 32% compared with 18% in BV patients without cerebellar signs. In a follow-up study on 82 BV-patients (mean age at the time of diagnosis 56.3 +/- 17.6 years), the frequency and degree of recovery or worsening of vestibular function over time were determined. The patients were reexamined 51 +/- 6 months after the first examination. Electronystagmography with bithermal caloric irrigation was analyzed by measurement of the mean peak slow-phase velocity (SPV) of the induced nystagmus. Statistical analysis of the mean peak SPV revealed a nonsignificant worsening over time (initial mean peak SPV 3.0 +/- 3.5 degrees/s vs. 2.1 +/- 2.8 degrees/s). Only patients with BV due to meningitis exhibited an increasing, but nonsignificant SPV (1.0 +/- 1.4 degrees/s vs. 1.9 +/- 1.6 degrees/s). Forty-three percent of patients subjectively rated the course of their disease as stable, 28% as worsened, and 29% as improved.

Long-term prophylactic treatment of attacks of vertigo in Menière's disease--comparison of a high with a low dosage of betahistine in an open trial.

CONCLUSION: Despite the considerable limitations of an open, non-masked trial, particularly in Menière's disease (MD), a higher dosage of betahistine-dihydrochloride and a long-term treatment seems to be more effective than a low dosage and short-term treatment. OBJECTIVE: To evaluate the prophylactic effects of a low versus high dosage long-term treatment with betahistine-dihydrochloride on the number of attacks in MD. PATIENTS AND METHODS: We performed an open, non-masked trial, in which patients with MD received either a low dosage of betahistine-dihydrochloride (16 or 24 mg tid) or a higher dosage of 48 mg tid for at least 12 months. The outcome measure was the number of attacks per month during a 3-month period. Non-parametric tests and a random effects model were used for statistical analysis. RESULTS: A total of 112 patients were included in the analysis: 50 received betahistine-dihydrochloride in a low dosage (16 mg tid, n=21, 24 mg, n=29) and 62 received 48 mg tid. Follow-up examination every 3 months showed that the number of attacks per month decreased in both groups over time. For instance, after 12 months the mean (median) number of attacks dropped from 7.6 (4.5) to 4.4 (2.0) (p<0.0001) in the low-dosage group, and from 8.8 (5.5) to 1.0 (0.0) (p<0.0001) in the high dosage group. The number of attacks after 12 months was significantly lower in the high dosage group than in the low dosage group (p(12M)=0.0002). The treatment was well tolerated in both groups.

Assessment of potential cardiotoxic side effects of mitoxantrone in patients with multiple sclerosis.

Previous studies showed that mitoxantrone can reduce disability progression in patients with multiple sclerosis (MS). There is, however, concern that it may cause irreversible cardiomyopathy with reduced left ventricular (LV) ejection fraction (EF) and congestive heart failure. The aim of this prospective study was to investigate cardiac side effects of mitoxantrone by repetitive cardiac monitoring in MS patients. The treatment protocol called for ten courses of a combined mitoxantrone (10 mg/m(2) body surface) and methylprednisolone therapy. Before each course, a transthoracic echocardiogram was performed to determine the LV end-diastolic diameter, the end-systolic diameter and the fractional shortening; the LV-EF was calculated. Seventy-three patients participated (32 males; age 48 +/- 12 years, range 20-75 years; 25 with primary progressive, 47 with secondary progressive and 1 with relapsing-remitting MS) who received at least four courses of mitoxantrone. Three of the 73 patients were excluded during the study (2 patients discontinued therapy; 1 patient with a previous history of ischemic heart disease developed atrial fibrillation after the second course of mitoxantrone). The mean cumulative dose of mitoxantrone was 114.0 +/- 33.8 mg. The mean follow-up time was 23.4 months (range 10-57 months). So far, there has been no significant change in any of the determined parameters (end-diastolic diameter, end-systolic diameter, fractional shortening, EF) over time during all follow-up investigations. Mitoxantrone did not cause signs of congestive heart failure in any of the patients. Further cardiac monitoring is, however, needed to determine the safety of mitoxantrone after longer follow-up times and at higher cumulative doses.

Diagnostic pitfalls in patients with hypoxic brain damage: three case reports.

OBJECTIVE: Our aim was to assess the possible diagnostic pitfalls in three patients with hypoxic brain damage who had partly conflicting clinical, biochemical, and electrophysiological data and were in a persistent vegetative state (PVS) following cardiac arrest (CA). METHODS: Serum concentrations of the destruction proteins, neuron-specific enolase (NSE) and protein S-100B (S-100B), were measured on days 1-3, and 7; somatosensory evoked potentials (SEPs) were recorded within 48 h and on day 7 after CA. RESULTS: Two patients had significantly increased concentrations of NSE and S-100B during the first 3 days after CA, a finding that indicates ongoing neuronal destruction. In contrast, the SEPs of these patients were normal or showed only a diminished amplitude configuration. In the third patient the SEPs demonstrated a bilateral loss of cortical responses repeatedly, but both destruction proteins were only slightly above the upper normal values on all study days. CONCLUSION: Our findings demonstrate that a poor prognosis can only be established if either SEPs, NSE, or S-100B are very abnormal. The conflicting results in our patients indicate that variable values may reflect different patterns of neuropathological damage caused by diffuse hypoxia. We, therefore, favour a multi-modal approach with a combination of clinical, biochemical, and electrophysiological investigations in order to predict neurological outcome after CA reliably.

Methylprednisolone, valacyclovir, or the combination for vestibular neuritis.

BACKGROUND: Vestibular neuritis is the second most common cause of peripheral vestibular vertigo. Its assumed cause is a reactivation of herpes simplex virus type 1 infection. Therefore, corticosteroids, antiviral agents, or a combination of the two might improve the outcome in patients with vestibular neuritis. METHODS: We performed a prospective, randomized, double-blind, two-by-two factorial trial in which patients with acute vestibular neuritis were randomly assigned to treatment with placebo, methylprednisolone, valacyclovir, or methylprednisolone plus valacyclovir. Vestibular function was determined by caloric irrigation, with the use of the vestibular paresis formula (to measure the extent of unilateral caloric paresis) within 3 days after the onset of symptoms and 12 months afterward. RESULTS: Of a total of 141 patients who underwent randomization, 38 received placebo, 35 methylprednisolone, 33 valacyclovir, and 35 methylprednisolone plus valacyclovir. At the onset of symptoms there was no difference among the groups in the severity of vestibular paresis. The mean (+/-SD) improvement in peripheral vestibular function at the 12-month follow-up was 39.6+/-28.1 percentage points in the placebo group, 62.4+/-16.9 percentage points in the methylprednisolone group, 36.0+/-26.7 percentage points in the valacyclovir group, and 59.2+/-24.1 percentage points in the methylprednisolone-plus-valacyclovir group. Analysis of variance showed a significant effect of methylprednisolone (P<0.001) but not of valacyclovir (P=0.43). The combination of methylprednisolone and valacyclovir was not superior to corticosteroid monotherapy. CONCLUSIONS: Methylprednisolone significantly improves the recovery of peripheral vestibular function in patients with vestibular neuritis, whereas valacyclovir does not.

Early prediction of neurological outcome after cardiopulmonary resuscitation: a multimodal approach combining neurobiochemical and electrophysiological investigations may provide high prognostic certainty in patients after cardiac arrest.

A reliable and reproducible method for precisely predicting the neurological outcome of patients with hypoxic-ischemic encephalopathy after cardiac arrest is urgently needed in neurological intensive care units. We prospectively investigated the predictive power of serum concentrations of neuron-specific enolase (NSE) and protein S-100B (S-100B) measured on days 1, 2, 3 and 7 as well as somatosensory-evoked potentials (SEPs) recorded within 48 h and on day 7 after cardiopulmonary resuscitation (CPR) in 27 patients (14 females, 13 males; mean age 61.3 +/- 17.3 years) with hypoxic-ischemic encephalopathy. During the first 7 days after CPR, median values of NSE and S-100B were increased in patients who remained unconscious after CPR compared to those patients who regained consciousness (significance up to < or =0.001). The best predictor of negative outcome was an NSE cutoff point > or =43 microg/l on day 2; this had a sensitivity of 90.9% and a specificity of 100%. Additional use of S-100B on day 2 did not increase sensitivity, but this could be markedly increased by combining NSE and S-100B on days 1, 3 and 7. SEPs showing bilateral loss of cortical responses identified patients who did not regain consciousness with a specificity of 100%.