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.

Pharmacotherapy of vestibular disorders and nystagmus.

Vertigo and dizziness are with a life-time prevalence of ~30% among the most common symptoms and are often associated with nystagmus or other oculomotor disorders. The prerequisite for a successful treatment is a precise diagnosis of the underlying disorder. In this overview, the current pharmacological treatment options for peripheral and central vestibular, cerebellar, and oculomotor disorders including nystagmus are described. There are basically seven groups of drugs that can be used (the "7 As"): antiemetics; anti-inflammatory, anti-Menière's, and antimigraine medications; antidepressants, anticonvulsants, and aminopyridines. In acute vestibular neuritis, recovery of the peripheral vestibular function can be improved by treatment with oral corticosteroids. In Menière's disease, a long-term high-dose treatment with betahistine-dihydrochloride (at least 48 mg three times daily) had a significant effect on the frequency of the attacks; the underlying mode of action is evidently an increase in inner-ear blood flow. The use of aminopyridines is a well-established therapeutic principle in the treatment of downbeat and upbeat nystagmus as well as episodic ataxia type 2 and cerebellar gait disorders. As was shown in animal experiments, these potassium channel blockers increase the activity and excitability and normalize irregular firing of cerebellar Purkinje cells. They evidently augment the inhibitory influence of these cells on vestibular and deep cerebellar nuclei. A few studies showed that baclofen improves periodic alternating nystagmus; gabapentin and memantine improve pendular and infantile nystagmus. However, many other eye-movement disorders such as ocular flutter, opsoclonus, central positioning, and see-saw nystagmus are still difficult to treat. Although substantial progress has been made, further state-of-the-art trials must still be performed on many vestibular and oculomotor disorders, namely Menière's disease, vestibular paroxysmia, vestibular migraine, and many forms of central eye-movement disorders.

Neurocysticercosis presenting as a vertical one-and-a-half syndrome with associated contralesional horizontal gaze paresis.

We describe a patient presenting with vertical one-and-a-half syndrome and concomitant contralesional horizontal gaze paresis as the result of a solitary neurocysticercosis (NCC) lesion in the right midbrain extending into the thalamomesencephalic junction. The patient received an albendazole-dexamethasone course which resulted in resolution of his symptoms. The neuro-ophthalmological complications of NCC are reviewed and the clinical topography of the neuro-ophthalmological findings of this unusual observation are discussed.

Downbeat nystagmus caused by thiamine deficiency: an unusual presentation of CNS localization of large cell anaplastic CD 30-positive non-Hodgkin's lymphoma.

A 24-year-old woman with a large cell anaplastic CD 30-positive T-cell non-Hodgkin's lymphoma (NHL) developed downbeat nystagmus, anisocoria, and oscillopsia. Prior to overt cerebral invasion by NHL, she had a thiamine deficiency with very low thiamine concentrations in the CSF, probably caused by protracted vomiting and increased vitamin B1 consumption by intrathecal tumor cells. We believe that her neurologic symptoms were caused -- at least partly -- by thiamine deficiency, as she reacted well to thiamine supplementation at the beginning of treatment.

[Antihypertensive study of xingnao qingxuan recipe].

OBJECTIVE: To observe the effect of decreasing blood pressure of Xingnao Qingxuan Casuples. METHOD: The blood pressure in normal and anesthetised cats was examined with direct method, the blood pressure in the conscious SHR was obtained by indirect method. RESULTS: Duodenuos administration(id) of XQC of 2.8 g/kg produced a decrease of blood pressure in normal cats; XQC of 1.4, 2.8 and 5.6 g/kg once a day for 14 days produced a dose-dependent reduction of blood pressure in SHR, 3-4 days after administration the blood pressure returned to the level before but the change was not significant. With gastric administration of XQC of 2.8 and 5.6 g/kg for 3 times, the incubation period of eyeball tremor induced by chloroform by dropping into the ear was prolonged by 14.4% and 13.0%, and the keeping time shortened by about 33.3% and 23.3% respectively. Brain basic arterial spasm induced by KCl or 5-HT in dog was relaxed obviously by XQC in vitro experiment. CONCLUSION: XQC has the effect of reducing blood pressure resisting dizziness, which is related to the diastole of brain blood vessel.

[Clinical and experimental studies of royal made ping an dan on treatment of motion sickness].

This paper presents the results of clinical observation and experimental research of Royal Made Ping An Dan (RPAD) of the Imperial Hospital of Qing Dynasty. The clinical results showed that RPAD was effective in treating 343 patients with motion sickness, and their average time for producing effect was 24.1 +/- 13.5 minutes. The total effective rates of dramamine group and Ren Dan group were 69.4% and 67.7% respectively, the latter included 45.7% of basically cured and 55.0% of markedly effective cases. There were significant differences among these groups (P < 0.05-0.01). It revealed that the effect of RPAD was better than that of dramamine and Ren Dan. According to laboratory findings, RPAD had the ability of alleviating symptoms of motion sickness and inhibiting eyeball tremor and improving meningeal microcirculation of experimental animals.

[Early complications following stapedectomy--surgical or conservative treatment?]. / Frühkomplikationen nach Stapedektomie--operative oder konservative Behandlung?

The incidence of sensorineural hearing loss after stapedectomy ranges from 0.6% to 5%. There is evidence that reparative granuloma is a major cause: most authors report that it requires urgent surgery, but this view is not universally accepted. This study analyses 14 stapedectomies that resulted in a sudden or gradual sensorineural hearing loss, often combined with vertigo, and presenting between 1 and 6 weeks after an initial hearing improvement. All patients were treated immediately with a combined infusion of an antibiotic, a corticosteroid and a plasma expander. The sensorineural hearing loss began to improve compared with pre-operative values 9 days later. Thus drug therapy might be sufficient in most cases of sensorineural hearing loss early after stapedectomy, and surgery can be restricted to patients with perilymph fistulae.

Calcium entry blockers in the treatment of vertebrobasilar insufficiency.

The influence of different calcium entry blockers on the vestibular system was investigated. The paper reports results from animal experiments and also from clinical studies with flunarizine and nimodipine. An animal experimental model of vertebrobasilar insufficiency was developed. The effect of the two drugs on the vestibular nystagmus was studied in Alsatian dogs before and after occluding one vertebral artery. In order to analyze the influence of the drugs on the vestibular nystagmus and on the clinical symptoms in patients with vertebrobasilar insufficiency, different open and double-blind studies were performed.