Workshop IV: drug treatment guidelines for the long-term management of Parkinson's disease.

An attempt was made to establish a decision algorithm for the treatment of idiopathic Parkinson's disease at various stages and in different subgroups such as akinetic-rigid or tremor dominance type. We suggest treating young patients with selegiline and a dopamine agonist. In the tremor dominance type we use either budipine or a dopamine agonist. Due to levodopa-induced dyskinesia, we try to avoid levodopa in the early stages of the disease and use it only later in more advanced situations in a combination therapy with dopamine agonists. Since IPS is not only based upon dopamine deficiency but also on resulting glutamatergic overstimulation, we advocate the use of a glutamate antagonist such as amantadine or budipine. Catechol-O-methyl inhibitors are very helpful when wearing-off occurs. Anticholinergics are only used in the early stages of tremor-dominant IPS because we fear enhancing the risk of dementia.

Once-daily versus twice-daily vigabatrin: is there a difference? The results of a double-blind pilot study.

PURPOSE: Vigabatrin (VGB) has been approved in Europe and is prescribed for either once or twice-daily administration. This choice has been based on the pharmacodynamic activity of VGB. The purpose of this study was to compare the efficacy and tolerability of these two different medication regimens. METHODS: The study design was a double-blind randomized two-period cross-over study in adults who had responded to add-on VGB for previously uncontrolled seizures. Each study period consisted of three months. Patients were maintained on the same daily dose of VGB to which they had demonstrated a clinical response. In addition to the primary efficacy criteria of seizure frequency on the two treatment regimens, this study included blinded ratings of overall efficacy and "well being" by both physician and patient. The primary tolerability criterion was the reported incidence of adverse events by phase. RESULTS: Fifty patients were initially entered into the study, and 13 patients withdrew before completion, only one reported as due to an adverse event. There was no statistical difference in seizure frequency or the tolerability of the medication. Blinded physician and patient rating scales for seizure control, and patient well being showed a nonstatistical trend toward once-daily administration as compared with twice-daily administration. CONCLUSIONS: This clinical study provides support for the pharmacological evidence that this preparation may be administered on a once or twice daily basis, depending on the individual patient's preference, total dosage and co-medication.

Acute trimethyltin limbic-cerebellar syndrome.

An acute limbic-cerebellar syndrome was seen in six industrial workers who inhaled trimethyltin (TMT). Clinical features included hearing loss, disorientation, confabulation, amnesia, aggressiveness, hyperphagia, disturbed sexual behavior, complex partial and tonic-clonic seizures, nystagmus, ataxia, and mild sensory neuropathy. Severity paralleled maximal urinary organotin levels. One patient died and two remained seriously disabled.

Normomorphic sialidosis in two female adults with severe neurologic disease and without sialyl oligosacchariduria.

Two female patients of German origin, aged 38 and 21 years, with myoclonus epilepsy and cerebellar ataxia, but without dysmorphic signs and dementia, were found to excrete normal amounts of sialyl oligosaccharides in their urine. The younger patient showed cherry red spots in her ocular fundi. The older patient had a brother with an autopsy-proven neuronal storage disease compatible with sialidosis, and in her rectal biopsy lamellar inclusion bodies were detected. Enzyme assays in cultured fibroblasts of both patients revealed a profound but incomplete deficiency of oligosaccharide sialidase activity and normal beta-galactosidase activity. Adult sialidosis was diagnosed in both patients. In their fibroblasts, moderate elevations of bound sialic acid could also be measured. The small residual sialidase activity, which in the older patient had a normal KM value, is considered responsible for the late onset and slow clinical course of the disease. It is concluded that in adult sialidosis the extraneural storage process can be difficult to demonstrate in terms of metabolite accumulation or excretion during the course of intraneuronal storage.

Ocular counterrolling. Some practical considerations of a new evaluation method for diagnostic purposes.

Ocular counterrolling (OCR) data taken from the literature (12 publications) were used to test the best fit (least-square fit) of these measurements with respect to three mathematical models: a sine relation between OCR and the lateral tilt stimulus, a complex cosine-square relation, and a logarithmic relation between OCR gain and tilt. The latter proved to be the best fitting function. On the basis of this model, we attempted to define a physiological transfer function between OCR gain and tilt, which could serve as a reference of normal population, assuming healthy subjects for the investigations applied. Comparison of this physiological range with pathological data demonstrated marked differences between them. The mathematical simplicity of a logarithmic model permits rapid analysis of clinical OCR examinations, and a classification of the findings.

European vestibular experiments on the Spacelab-1 mission: 2. Experimental equipment and methods.

A series of vestibular experiments were performed in conjunction with the first Spacelab mission, consisting of sets of pre-, in- and postflight tests. A multipurpose experimental apparatus used for the diverse flight and ground tests is presented. Additional apparatus together with the multi-purpose package were used in the baseline data collection facility at the landing site at NASA Dryden Flight Research Facility for the ground tests. The tests involved optokinetic, caloric and mechanical (whole-body or head-alone) stimulation. The latter included linear acceleration in the subject's x, y and z axes, static roll and yaw about an earth-vertical axis. Physiological parameters such as electro-oculogram (EOG), blood-volume-pulse (BVP), respiration, as well as the stimulus variables such as acceleration and caloric temperature were transmitted to the ground and recorded there. The flight and ground testing schedules are outlined. Problems arising from this complex venture are discussed, and some suggestions are made for future improvement.

Physiological response to hyper- and hypogravity during rollercoaster flight.

Healthy male subjects--26--were flown in a Lear jet aircraft through rollercoaster and parabolic weightlessness flight. Eye movements, respiration, and blood volume pulse were recorded on magnetic tape. The same subjects underwent a battery of five vestibular tests in the laboratory on the ground. One subject in each flight was flown in an upright position, the other in a 90 degree foreward tilted head position. The foreward tilted subjects always reported motion sickness earlier and after fewer rollercoaster manoeuvres than the upright sitting subjects. It is concluded that the susceptibility to changes of X-axis acceleration is higher than to changes of Z-axis acceleration. Correlation was found between the ability to estimate the subjective vertical (modified Müller-Aubert-test), optokinetic nystagmus asymmetries, and susceptibility to rollercoaster flight sickness.

A model for vestibular function in altered gravitational states.

During evolution, the vestibular organ was made to serve mainly two purposes: 1) to guide eye movements during sharp turns, so that the point of fixation in the visual field can be kept steady, a function accomplished by the semicircular canal system and 2) to indicate the terrestrial vertical, so that upright posture and gait can be maintained even in the dark. The otolith system serves the latter purpose. Since the function of the semicircular canal system does not depend on gravity, it is not grossly disturbed by gravitational levels different from 1 g. The proper function of the otolith system depends entirely on the presence of a gravitational force vector of 9.8/m/sec2 directed towards the center of the earth. This system therefore malfunctions when the amplitude of the combined gravito-inertial load is different from 1 g and also when the direction of the sensed gravitational pull is "contaminated" by additional inertial reactive forces as during horizontal acceleration. The effect of such inertial stimulations is probably even stronger in a weightless environment, in which case the background stimulation of terrestrial gravity is absent. Moreover, minor mass differences between the otolithic membranes of the left and right inner ear, even if well compensated on the ground, might lead to malcompensation in weightlessness as well as in hypergravity. A hypothetical model is developed to describe in the central nervous system compensating mechanisms in hypo- and hypergravitational states. The "space-sled" is introduced as a new research tool and recommendations are made for a prophylactic training regimen to reduce or prevent space sickness.

[Refsum's syndrome (author's transl)]. / Refsum-Syndrom (Heredopathia atactica polyneuritiformis). Klinik, Diagnostik und diätetische Behandlung.

Heredopathia atactica polyneuritiformis (Refsum's syndrome) is an autosomal recessively inherited lipidosis characterized by the following signs: peripheral hypertrophic polyneuropathy, cerebellar ataxia, atypical retinitis pigmentosa with night blindness and concentric limitation of the visual fields, anosmia, inner ear hearing disturbances, skeletal anomalies, ichthyotic skin changes, raised protein in the CSF without a cellular increase, and non-specific ECG changes. Biochemically it is a lipidosis with atypical increase of phytanic acid in blood, CSF, and tissues. The metabolic defect results from a degradation disturbance of exogenous phytanic acid. The report of a patient whose clinical picture plus chemical, neurophysiological and histological results led to the diagnosis of Refsum's syndrome is presented. Using a low phytol- and phytanic-acid diet a marked decrease of phytanic acid in the serum and an improvement of the clinico-neurological signs were observed.