SCA17 is a rare type of autosomal dominant spinocerebellar ataxia caused by a CAG/CAA expansion in the gene encoding the TATA-binding protein (TBP). We screened for triplet expansion in the TBP gene 110 subjects with progressive cerebellar ataxia and 94 subjects with Huntington-like phenotype negative at specific molecular tests. SCA17 mutation-positive subjects were found in both groups of patients. Expanded alleles with > or = 44 CAG/CAA repeats were identified in 11 individuals and in 4 non-symptomatic relatives. Eleven de novo diagnosed patients and four patients previously reported underwent extensive clinical, neuroradiological and oculographic examination. Cerebellar signs and symptoms were present in all cases; 80% of the patients had mild to severe cognitive deficits; 66% of patients showed choreic movements; pyramidal signs, bradykinesia and dystonia were observed in approx 50% of the cases. MRI demonstrated cortical and cerebellar atrophy in all patients, whereas neurophysiological examination excluded signs of peripheral nervous system involvement. Oculographic examinations were performed in 9 out of 15 patients and showed a distinct pattern of oculomotor abnormalities, characterized by impairment of smooth pursuit, defects in the saccade accuracy, normal saccade velocity, hyperreflexia of vestibuloocular reflexes, and absence of nystagmus. In summary, this study presents one of the largest series of SCA17 patients in Europe. In our group of patients, SCA17 represents the third most frequent SCA genotype. Our clinical data confirm the large variability in SCA17 phenotypic presentation, and indicate that a peculiar combination of neuroradiological, electrophysiological and oculomotor findings is recognizable in SCA17.

Chronic cerebrospinal venous insufficiency might be the anatomical background, which provides a predisposing factor for the development of endolymphatic hydrops in MD patients.

Patients with multiple sclerosis (MS) frequently report symptoms related to vestibular disorders in the course of their disease. At present, the fundamental tests assessing vestibulospinal involvement are posturography and vestibular evoked myogenic potentials (VEMPs). While posturography cannot be performed in every subject requiring minimal stance control, VEMPs do not require any specific skill on the part of the subjects and they may be investigated in all patients able to sit. VEMPs were recorded for 40 patients (17 men, 23 women; mean age 38 years, range 17-71 years) fulfilling diagnostic criteria of clinically defined MS, by means of rarefaction clicks, recording modulation of sterno-cleido-mastoideus tonic contraction saccule-mediated modulation. VEMPs were found to be abnormal in 28 of 40 patients. In 18 of the cases the VEMPs were asymmetric, i.e., had a prolonged latency on one side. In six cases latency was increased on both sides (mean delay 4.1 ms). In four subjects VEMPs were absent on one side. C oncordance with clinical findings of presence/absence of brainstem involvement was found in 55% and with MRI findings in 65% of the cases. A bnormal VEMPs indicated brainstem dysfunction in four patients (10%) with normal MRI and no specific clinical signs.

Stress is a significant factor influencing the clinical course of tinnitus. Auditory system is particularly sensitive to the effects of different stress factors (chemical, oxidative, emotional, etc.). Different stages of reaction (alarm, resistance, exhaustion) lead to different characteristics of tinnitus and different therapeutic approaches. Individual characteristics of stress reaction may explain different aspects of tinnitus in various patients with different responses to treatment, despite similar audiological and ethiological factors. A model based on individual reactions to stress factors (stress reaction tinnitus model) could explaintinnitus as an alarm signal, just like an ‘alarm bell’, informing the patient that something potentially dangerous for subject homeostasis is happening. Tinnitus could become a disabling symptom when the subject is chronically exposed to a stress factor and is unable to switch off the alarm. Stress signals, specific for each patient, have to be identified during the ‘alarm’ phase in order to prevent an evolution toward the ‘resistance’ and ‘exhaustion’ phases. In these phases, identification of stressor is no more sufficient, due to the organization of a ‘paradoxical auditory memory’ and a ‘pathologically shifted attention to tinnitus’. Identification of stress reaction phase requires accurate otolaryngology and anamnesis combined with audiological matching tests (Feldman Masking Test, for example) and psychometric questionnaires (Tinnitus Reaction and Tinnitus Cognitive Questionnaires).

A new item response scale is presented, which measures the severity of self-reported balance deficits. The scale, DHIsf, is a short form of the Dizziness Handicap Inventory. The scale was constructed and validated by Rasch analysis. Rasch analysis was applied to rescore or remove any items misfitting, redundant, or off-target, until an optimal instrument was obtained. The 25-item, 3-level Dizziness Handicap Inventory was, thus, reduced to the 13-item, 2-level DHIsf. The retained items explore the domains of eye/head movements, full body activities, and mood alterations. Data were collected from 55 outpatients (63 +/- 13 yr; 43 females) attending otoneurological rehabilitation referral at a general hospital because of complaints of dizziness or imbalance. They were fully independent in ambulation and showed no evidence of major neurological or orthopedic diseases. Objective tests included brain computed tomography, sovraaorctic Doppler sonography, craniocorpography, static posturography, and nystagmography. The findings were categorized as pathologic, borderline, or normal. At least one examination was borderline or abnormal in 42 patients. The DHIsf was well targeted on this sample, with a mean score of 5.7/13 (standard deviation, 2.8; median, 5; range, 1-13). The Rasch statistics showed that the 13 items evenly fitted a hierarchy of difficulty within a homogeneous construct. A moderate but significant variance explanation of DHIsf measures was provided by a two-way analysis of variance model, with craniocorpography and nystagmography as independent categorical variables (r2 = 0.15; P = 0.018). When the clinical tests were individually taken into account, their outcome (dichotomized as abnormal v borderline or normal) could not be predicted by either of the DHIsf measures or raw scores (logistic regression). The DHIsf compares favorably with the original Dizziness Handicap Inventory, shows some consistency with the instrumental findings, and provides original information on the severity of imbalance syndromes, as it is seen from the patient's perspective.