Mitochondrial 12S rRNA susceptibility mutations in aminoglycoside-associated and idiopathic bilateral vestibulopathy.

The mitochondrial 12S rRNA is considered a hotspot for mutations associated with nonsyndromic (NSHL) and aminoglycoside-induced hearing loss (AIHL). Although aminoglycoside ototoxicity is the most common cause of bilateral vestibular dysfunction, the conceivable role of 12S rRNA mutations has never been systematically investigated. We sequenced the 12S rRNA of 66 patients with bilateral vestibulopathy (BV) with (n=15) or without (n=51) prior exposure to aminoglycosides, as well as 155 healthy controls with intact vestibular function (sport pilots), and compared these to 2704 published sequences (Human Mitochondrial Genome Database). No mutations with a confirmed pathogenicity were found (A1555G, C1494T), but four mutations with a hitherto tentative status were detected (T669C, C960del, C960ins, T961G). Due to their predominant occurrence in patients without aminoglycoside exposure, their detection in controls and a weak evolutionary conservation, their pathogenic role in vestibulocochlear dysfunction remains provisional.

Follow-up of vestibular function in bilateral vestibulopathy.

OBJECTIVE: Bilateral vestibulopathy (BV) leads to a bilateral deficit of the vestibulo-ocular reflex and has various aetiologies. The main goal of this study was to determine the frequency and degree of recovery or worsening of vestibular function over time. METHODS: 82 patients (59 males, 23 females; mean age at the time of diagnosis 56.3 (SD 17.6) years) were re-examined 51 (36) months after the first examination. All patients underwent a standardised neuro-ophthalmological and neuro-otological examination. Electronystagmography with bithermal caloric irrigation was analysed by measurement of the mean peak slow phase velocity (SPV) of the induced nystagmus. Patients evaluated the course of their disease in terms of balance, gait unsteadiness and health related quality of life. RESULTS: Statistical analysis of the mean peak SPV of caloric induced nystagmus revealed a non-significant worsening over time (initial mean peak SPV 3.0 (3.5) degrees/s vs 2.1 (2.8) degrees/s). With respect to subgroups of aetiology, only patients with BV due to meningitis exhibited an increasing, but non-significant SPV (1.0 (1.4) degrees/s vs 1.9 (1.6) degrees/s). Vestibular outcome was independent of age, gender, time course of manifestation and severity of BV. Single analysis of all patients showed that a substantial improvement > or = 5 degrees/s occurred in two patients on both sides (idiopathic n = 1, Sjögren's syndrome n = 1) and in eight patients on one side (idiopathic n = 6, meningitis n = 1, Menière's disease n = 1). In 84% of patients there was impairment of their health related quality of life (42% slight, 24% moderate, 18% severe). Forty-three per cent of patients rated the course of their disease as stable, 28% as worsened and 29% as improved. CONCLUSIONS: Our data support the view that more than 80% of patients with BV do not improve. Thus the prognosis of BV is less favourable than assumed.

The effect of nicotine on perceptual, ocular motor, postural, and vegetative functions at rest and in motion.

Nicotine has wellknown, unpleasant side effects, e.g., transient dizziness, nausea, and nicotine-induced nystagmus (NIN). To investigate factors influencing these effects, we addressed three questions: (1) Is the intensity of dizziness, nausea, NIN, and unsteadiness dependent on nicotine dosage? (2) Does the intensity of perceptual, ocular motor, vegetative effects, and postural imbalance correlate? (3) Do visual or vestibular motion stimuli produce and/or aggravate distressing dizziness and nausea? Sixty healthy non-smokers or occasional smokers participated; 40 were tested once before and six times after application of a nicotine nasal spray in doses of 1 mg or 2 mg with or without motion stimulation; 20 received a placebo nasal spray. Plasma nicotine concentrations were significantly related to nicotine dosage. Dizziness, nausea, NIN, and unsteadiness also depended on the nicotine dosage (p < 0.01).Nicotine blood concentration was a better predictor for the temporal dependence of nystagmus than nicotine dosage. Dizziness correlated highly with nausea (R = 0.63, p < 0.001). The degree of nicotine-induced nausea significantly correlated with postural imbalance. The time course of postural sway differed according to nicotine dosage and gender: for women, there was no clear relationship between sway magnitude and nicotine dosage, while men showed increased sway with higher dosage. Motion stimulation increased nicotine-induced dizziness and nausea, but did not significantly influence NIN or postural imbalance. Our data support the view that all measured adverse effects reflect dose-dependent nicotine-induced vestibular dysfunction. Additional motion stimulation aggravates dizziness and nausea, i.e., nicotine increases sensitivity to motion sickness.

[Polysomnographic as a therapeutic aid in of psychogenic-functioning paraplegia]. / Polysomnographie als therapeutische Hilfe bei psychogen-funktioneller Paraplegie.

The case of a patient with complete sensory and motor paraplegia for more than 1 year is presented. Leg movements were documented during sleep by video and electromyographic recording because a psychogenic cause of the symptoms was suspected. We showed the video to the patient, which illustrated that leg movements were possible. This resulted in fast and complete resolution of the neurologic symptoms. The patient has now been free of them for more than 3 years. This example suggests that the achievement of consciousness of normal motor function is a therapeutic approach for long-standing improvement of psychogenic paralysis.

[The effect of combined mitoxantrone and methylprednisolone therapy in primary and secondary progressive multiple sclerosis. An applied study in 65 patients]. / Kombinierte Mitoxantron-/Methylprednisolon-Behandlung bei primär und sekundär chronisch progredienter Multipler Sklerose. Eine Anwendungsbeobachtung bei 65 Patienten.

Mitoxantrone (mitox) has been shown to be effective for secondary progressive (SP) and relapsing-remitting multiple sclerosis (MS). The aim of this open trial was to evaluate the effects of combined mitox and methylprednisolone (MP) therapy on patients with primary progressive (PP)-MS or with SP-MS. We present here the results of an interim analysis done after the study had lasted 5 years. Sixty-five patients (20 with PP-MS and 45 with SP-MS) have been included so far. The treatment involved ten cycles of combined mitox and MP. The intervals between the individual cycles were systematically prolonged from 3 months initially to 12 months, so the complete treatment took a total of 57 months. Conclusion This interim analysis indicates that mitox combined with MP beneficially reduces the progression of disability in patients with PP-MS and SP-MS. Therefore, this therapy regimen can also be considered a feasible option for PP-MS.