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The SELEDO (from selegiline plus levodopa) study was carried out as a randomized, prospective, placebo-controlled, double- blind, multicenter long-term, 5-year trial to evaluate the possible advantages of combining selegiline and levodopa in the early treatment of Parkinson's disease. One-hundred-and-sixteen patients were randomized either to selegiline or placebo. Before starting the study medication, the levodopa dose was titrated to the individual requirements of each patient. The primary study end point (time when levodopa had to be increased by >50% of the titrated dose) was reached in 23 of 59 patients in the selegiline group and 26 of 48 patients in the placebo group. At the end of the 5 years' treatment period the rates derived from a life-table analysis were 50.4% in the selegiline group and 74.1% in the placebo group (P = 0.027, log-rank test). The median time to reach the primary end point was 4.9 years in the selegiline group and 2.6 years in the placebo group. In patients treated with selegiline, the mean levodopa dose changed only slightly over the 5 years of treatment compared to the initially titrated dose, but rose markedly in the placebo group, where the dose of levodopa had to be adjusted earlier than in the selegiline group. At the same time, the lower levodopa dosage in the selegiline group was accompanied by at least equal therapeutic efficacy (which is necessary for an unambiguous interpretation). Subgroup analyses showed greater benefit for selegiline treated) patients in the earlier stages. Long-term side effects appeared later in the selegiline group, although the difference was not significant. The early combination of selegiline and levodopa proved to be clearly superior to levodopa monotherapy.

Patients with Hashimoto’s encephalopathy (HE), a steroid-responsive disorder, associated with Hashimoto’s disease and high levels of thyroid-related autoantibodies usually present with a subacute onset of confusion, focal or generalized seizures. Frequent EEG abnormalities include generalized, rhythmic bifrontal or temporal slowing. Elevated protein levels or an intrathecal IgG synthesis may be present in cerebrospinal fluid (CSF). A 39-year-old woman underwent a relapsing course of myocloni and generalized seizures. Initially, thyroid function, thyroid-related autoantibody screening and cerebral MRI were unrevealing. CSF showed oligoclonal bands. Short-term treatment with high doses of prednisolone resolved the myocloni. During the 5th episode of myocloni, signs of hyperthyroidism and elevation of thyroid microsomal antibody titer developed. Hashimoto’s thyroiditis and HE were diagnosed. After subtotal thyroidectomy the patient remained asymptomatic.

A previous suggestion that antiepileptic drugs may induce color vision deficiencies prompted us to examine whether color vision deficiencies may occur at lower drug serum concentrations than those associated with symptoms of neurotoxicity. Eighty patients presenting with epilepsy received monotherapies of valproic acid, phenytoin, or carbamazepine; 18 patients did not receive antiepileptic drug therapy. Color vision was tested by the Farnsworth-Munsell 100-hue test, spectral sensitivity, and the newly developed tritan screening plates. Patients treated with phenytoin or carbamazepine developed blue-yellow color vision deficiencies. In contrast, patients exposed to valproic acid or receiving no drug treatment showed normal color vision. There was a significant correlation (p < 0.0001) between signs of neurotoxicity induced by phenytoin or carbamazepine and blue-yellow color vision deficiencies. In contrast, we found no correlation between these signs of neurotoxicity and the drug serum concentrations (p = 0.0637). Color vision testing in epileptic patients treated with phenytoin or carbamazepine appears to be a sensitive method for early detection and monitoring of clinical neurotoxicity.

In 1928, Hugo Friedrich Kufs reported on a family with cerebral, retinal, and cutaneous cavernous malformations. Since then, more than 300 families with inherited cavernous malformations have been reported. Genetic studies showed three loci, on chromosomes 7q21-q22 (with the gene CCM1), 7p15-p13 (CCM2), and 3q25.2-q27 (CCM3). The gene product of CCM1 is Krit 1 (Krev interaction trapped 1), a protein interacting with angiogenesis by various mechanisms. Recently, CCM2 has also been identified; its product is a protein which might have a function similar to that of Krit 1. However, the CCM3 gene has still not been found. In this study, we present clinical and genetic findings on 15 German families.

Both Marfan's syndrome and neurofibromatosis type 1 are hereditary, autosomal dominant conditions. Here, we report the rare case of a patient fulfilling the clinical criteria for both diseases. In the absence of a family history of either of the two conditions, two independent de novo mutations are the most likely cause.

The aim of this study was to assess cognitive function in patients with spinocerebellar ataxia type 6 (SCA6), an autosomal-dominantly inherited disease leading to a progressive cerebellar syndrome. In contrast to other SCA types, the pathological changes are mostly restricted to the cerebellum. Cognitive function was studied in 12 patients with genetically confirmed SCA6 (mean duration of disease: 9.2 +/- 11.6 years) and 12 age- and IQ-matched controls using a test battery comprising tests for IQ, attention, verbal and visuospatial memory, as well as executive function. While none of the SCA6 subjects had features of general intellectual impairment, only mild deficits in single subtests especially in fronto-executive tasks were observed, but without reaching statistical significance. Thus the current findings do not demonstrate severe cognitive dysfunction in SCA6.

Treosulfan is a bifunctional alkylating prodrug with activity against various solid tumors. To improve the outcome for patients with recurrent malignant glioma, we assessed the efficacy of intravenous treosulfan (6-10 g/m2 4-weekly) as salvage therapy for patients with recurrent or progressive glioblastoma (GB, n = 14) or anaplastic astrocytoma (AA, n = 2). All patients had prior involved-field radiotherapy and adjuvant nitrosourea-based chemotherapy. A total of 56 cycles were administered. Tumor responses were assessed radiologically and clinically prior to each cycle. All patients were assessable for toxicity, response and survival. There were no complete or partial responses (CR, PR). Two patients progressed after the first cycle, 14 patients had initially stable disease (SD). Median progression-free survival was 3.25 months for the GB patients. Five patients were progression-free at 6 months (30%), including the 2 AA patients. The 2 AA patients are stable at 22 months. Myelosuppression was the dose-limiting toxicity in this cohort of nitrosourea-pretreated patients. Treosulfan has modest activity in patients with recurrent malignant glioma. Further evaluation of treosulfan in chemonaive malignant glioma patients is warranted.

To study the involvement of pyramidal tracts and sensory pathways in multiple system atrophy (MSA).Evoked potential studies were performed in 45 MSA patients suffering from either MSA of cerebellar type (MSA-C) or MSA of parkinsonian type (MSA-P).Motor evoked potentials were normal in all MSA patients, whereas visual and somatosensory evoked potential abnormalities were found in about 40% of the MSA patients with no significant difference between the cerebellar (MSA-C) and parkinsonian (MSA-P) subgroup. Abnormal latencies of wave III in brainstem auditory evoked potentials were significantly more frequent in MSA-C.Abnormalities of somatosensory, visual and auditory evoked potentials are frequent findings in MSA, whereas abnormal motor evoked potentials are not a characteristic feature of the disease.

The hereditary ataxias are a heterogeneous group of inherited neurodegenerative disorders characterised by progressive ataxia that results from degeneration of the cerebellum and its afferent and efferent connections. With respect to the pathogenic mechanisms, the hereditary ataxias may be tentatively divided into three groups: (1) The recessive ataxias are induced by the functional impairment of a protein that is essential for the survival of specific neurons while the autosomal dominant ataxias are either caused by (2) mutations of genes coding for ion channels thus resulting in a channelopathy or by (3) a novel deleterious function of a extended polyglutamine sequence within the proteins encoded by the respective genes.

In cerebellar ataxia, kinematic aberrations of multijoint movements are thought to originate from deficiencies in generating muscular torques that are adequate to control the mechanical consequences of dynamic interaction forces. At this point the exact mechanisms that lead to an abnormal control of interaction torques are not known. In principle, the generation of inadequate muscular torques may result from an impairment in generating sufficient levels of torques or from an inaccurate assessment and prediction of the mechanical consequences of movements of one limb segment on adjacent joints. We sought to differentiate the relative contribution of these two mechanisms and, therefore, analyzed intersegmental dynamics of multijoint pointing movements in healthy subjects and in patients with cerebellar degeneration. Unrestrained vertical arm movements were performed at three different target movement velocities and recorded using an optoelectronic tracking system. An inverse dynamics approach was employed to compute net joint torques, muscular torques, dynamic interaction torques and gravitational torques acting at the elbow and shoulder joint. In both groups, peak dynamic interaction forces and peak muscular forces were largest during fast movements. In contrast to normal subjects, patients produced hypermetric movements when executing fast movements. Hypermetric movements were associated with smaller peak muscular torques and smaller rates of torque change at elbow and shoulder joints. The patients' deficit in generating appropriate levels of muscular force were prominent during two different phases of the pointing movement. Peak muscular forces at the elbow were reduced during the initial phase of the movement when simultaneous shoulder joint flexion generated an extensor influence upon the elbow joint. When attempting to terminate the movement, gravitational and dynamic interaction forces caused overshooting extension at the elbow joint. In normal subjects, muscular torque patterns at shoulder and elbow joint were synchronized in that peak flexor and extensor muscular torques occurred simultaneously at both joints. This temporal pattern of muscular torque generation at shoulder and elbow joint was preserved in patients. Our data suggest that an impairment in generating sufficient levels of phasic muscular torques significantly contributes to the patients' difficulties in controlling the mechanical consequences of dynamic interaction forces during multijoint movements.

Quantitative caloric testing is considered to be one of the most sensitive parameters in the diagnosis of peripheral vestibular disorders. In the past, because of limitations in the methods, the evaluation of the caloric response was restricted to mainly lateral semicircular canal functions. In this study, the authors tried to extend caloric testing to the function of all semicircular canals by using three-dimensional (3-D) analysis techniques.The authors studied in seven normal subjects 3-D eye movement responses to air caloric of the right ear with the subjects positioned in standard caloric position (lateral semicircular canal vertical) or such that one of the three semicircular canals of the right side was horizontal. Movement of the left eye was measured in 3-D with a dual-magnetic search coil. During stimulation, 10 seconds of maximum response were selected and desaccaded to yield the slow-phase velocity profile. From this profile, the average magnitude and direction of the eye rotation axis (velocity vector) were calculated in head coordinates.In all subjects, in standard caloric position, warm caloric produced eye velocity vectors that clustered closely along the direction expected from an excitation of the right lateral semicircular canal. When the subjects were positioned with one of the vertical semicircular canals horizontal, the orientation of the velocity vectors shifted toward a direction expected from the combined excitation of the lateral and the other vertical semicircular canal and vice versa.The 3-D eye movement recordings during caloric stimulation in different head positions allow the evaluation of the function of all semicircular canals.

Apoptotic neuronal death is a key mechanism that regulates the elimination of neuronal precursor cells during the development of the mammalian brain. The principal action of neurotrophins such as nerve growth factor is probably the suppression of the preexistent machinery of programmed cell death that is readily activated in neurons deprived of neurotrophins. Potassium-mediated neuronal depolarization prolongs neuronal survival in vitro and has become a major model of examining neuronal apoptosis. Apoptosis induced by potassium deprivation triggers a lethal cascade of events that includes specific RNA and protein synthesis, induction of interleukin 1-converting enzyme-like protease activity, and generation of free radicals. Neuronal susceptibility to apoptosis is also regulated by the expression of bcl-2 family proteins. Current research focuses on the significance of these findings for the premature death of adult neurons in human neurodegenerative diseases.

1. What is the neural mechanism of vestibuloocular reflex (VOR) cancellation when a subject fixates a target moving with the head? One theory is that the moving target evokes pursuit eye movements that add to and cancel the VOR. A recent finding with implications for this theory is that eye velocity vectors of both pursuit and the VOR vary with eye position, but in different ways, because pursuit follows Listing's law whereas the VOR obeys a “half-Listing” strategy. As a result, pursuit cannot exactly cancel the VOR in most eye positions, and so the pursuit superposition theory predicts an eye-position-dependent pattern of residual eye velocities during cancellation. To test these predictions, we measured eye velocity vectors in humans during VOR, pursuit, and cancellation in response to torsional, vertical, and horizontal stimuli with the eyes in different positions. 2. For example, if a subject is rolling clockwise (CW, frequency 0.3 Hz, maximum speed 37.5 deg/s) while looking 20 deg up, the VOR generates an eye velocity that is mainly counterclockwise (CCW), but also leftward. If we then turn on a small target light, located 20 deg up and moving with the subject, then pursuit superposition predicts that the CCW component of eye velocity will shrink and the horizontal component will reverse, from leftward to rightward. This pattern was seen in all subjects. 3. Velocities depended on eye position in the predicted way; e.g., when subjects looked 20 deg down, instead of 20 deg up, during CW roll, the reversal of horizontal eye velocity went the other way, from rightward to leftward. And when gaze was 20 deg right or left, analogous reversals occurred in the vertical eye velocity, again as predicted. 4. Analogous predictions for horizontal and vertical stimulation were also borne out by the data. For example, when subjects rotated rightward while looking 20 deg up, the VOR response was leftward and CCW. When the target light switched on, the torsional component of the response reversed, becoming CW. And analogous predictions for other eye positions and for vertical stimulation also held. 5. For all axes of stimulation and all eye positions, eye velocity during cancellation was roughly parallel with the gaze line. This alignment is predicted by pursuit superposition and has the effect of reducing retinal image slip over the fovea. 6. The fact that the complex dependence of eye velocity on the stimulation axis and eye position predicted by pursuit superposition was seen in all subjects and conditions suggests strongly that the VOR indeed is canceled additively by pursuit. However, eye velocities during cancellation were consistently smaller than predicted. This shrinkage indicates that a second mechanism, besides pursuit superposition, attenuates eye velocities during cancellation. The results can be explained if VOR gain is reduced by approximately 30%, and if, in addition, pursuit is driven by retinal slip rather than reconstructed target velocity in space.

We have recently developed a method of long-term EMG recording (Bacher et al., 1989), which has proven suitable for the quantification of pathological tremor. In the present paper we show that (1) the principal parameters of the method (tremor occurrence, tremor intensity, tremor frequency) are highly reproducible with intraclass correlation coefficients in the order of 0.9, (2) that the method has both a high specificity (87.5%) and sensitivity (96%) for detection of pathological tremor, and (3) that it can be useful for examining agonist-antagonist muscle activation under everyday conditions.

Cryptococcosis is an important cause of lymphocytic meningitis, especially but not necessarily in immunocompromised patients. We present the case of a 23-year-old man with a severe and rapid course of a cryptococcal meningoencephalitis, which led to visual and hearing loss, psychotic illness and radiculopathy. There was no evidence of immunodeficiency. Treatment with amphotericin B and flucytosine led to improvement of the symptoms but did not eradicate the micro-organisms from the cerebrospinal fluid (CSF). Maintenance therapy with fluconazole was necessary and led to improvement of the CSF pathology.

In order to find a non-invasive method for determining the hemispheric dominance for language, we studied cortical activation patterns during language processing by means of electrophysiological techniques: DC-potentials were recorded from frontal, central, temporal and parietal electrode positions in 28 right-handed normal subjects and in 16 patients with a history of transient loss of speech and known hemispheric dominance. Subjects were asked to find as many synonyms as possible within 6 seconds to either a concrete or an abstract noun. This task caused a highly significant left-hemispheric lateralization over frontal and central, but not over temporal and parietal cortical areas. Search for synonyms to abstract nouns yielded frontal left-hemispheric dominance in 93% of all normal subjects, search for synonyms to concrete nouns in 85%. Inter-electrode correlation coefficients were higher during processing of abstract word categories than during processing of concrete categories. In all patients, frontal and central lateralization corresponded to their hemispheric dominance as determined from clinical data. Advantages as well as inconveniences of this technique are discussed and compared to other invasive and noninvasive tools of assessing speech lateralization.

Sequential postural adjustments associated with the task of rising on tip-toes were investigated in a reaction time paradigm in 30 normal subjects, 10 patients with Parkinson's disease and 2 patients with cerebellar lesions. The typical motor pattern observed in normal subjects consists of preparatory activity in tibialis anterior (TA, shifting the body forward) and quadriceps femoris (QUA, stabilizing the knee joint) followed by executional activity in triceps surae (TS) resulting in the movement itself. Shortening of TS without preparation would result in shifting the body backward and in flexion of the knee. The coordinated pattern of motor activities is obviously adapted to functional demands. Leaning forward or backward prior to the movement results in additional adaptive changes in the timing of preparatory versus executional EMG activity, and in the amount of preparatory muscle force. The basic pattern of preparatory (TA and QUA) and executional (TS) activity was preserved in most patients with Parkinson's disease. Reaction times were normal or only moderately delayed. Time intervals between postural preparation and execution were also normal. But trial to trial variation of reaction times was increased. In the two patients with cerebellar disorders, motor preparation in QUA was delayed beyond TS onset. EMG activity was tonic and cocontraction of antagonistic muscles occurred. The basic pattern of motor preparation and execution was again preserved. It must therefore be generated outside the basal ganglia and the cerebellum. The temporal coordination of muscular activity within each and between the two components and scaling of muscle force are under cerebellar control.

To further elucidate possible central plastic adaptive processes during the recovery from a unilateral peripheral vestibular lesion, we investigated vestibular functions in humans over a period of 2 months after an acute unilateral labyrinthine lesion. A unilateral peripheral vestibular lesion creates both a tonic imbalance that causes spontaneous nystagmus and a decrease and directional asymmetry of dynamic vestibular responses. We establish that the tonic imbalance expressed by the spontaneous nystagmus rapidly decreased (similar to other species), whether the lesion remained complete or not. This rebalancing, in the case of complete lesions, is at least partly due to restoration of central vestibular tone on the lesioned side. This restoration of tone also explains, in the case of a complete lesion, the recovery of dynamic vestibular responses for high-velocity inhibitory stimulation of the remaining labyrinth. A clear recovery of the dynamic response for excitatory stimulation of the remaining labyrinth cannot be proven, as has been shown in monkeys during the first 4 days after a unilateral vestibular lesion. This is probably due to the fact that in our patients the first recording could not be performed before day 3 after the onset of symptoms. Therefore, any fast dynamic recovery may have been missed.

(1) Methods have been developed to measure, analyse and document postural sway. The main parameters studied were: average sway amplitude; length of the sway path per unit time; sway direction and sway position histograms; and the frequency spectra of the antero-posterior and lateral sway components. (2) Postural ataxia was quantitatively studied in three groups of patients with cerebellar lesions: (a) late atrophy of the anterior lobe, (b) tumours of the cerebellar hemisphere and (c) tumours within the vestibulo-cerebellum. Characteristic differences were found. (3) Patients with anterior lobe lesion show a specific 3 Hz postural tremor in the antero-posterior direction. The tremor can be evoked by sudden destabilization in incipient cases. Less characteristic and smaller in amplitude is a mainly lateral sway component with an average frequency of 0.5 Hz. This is also seen in cases with spinal ataxia. Visual stabilization of posture is frequently preserved. Its amount does not correlate with general instability of posture. Tremor and characteristically exaggerated intersegmental responses between head, trunk, hips and legs are interpreted as the consequence of hyper-excitability of postural reflexes in these patients. (4) Patients with lesions of the hemispheres show only slight postural instability without directional preference. Their sway parameters with eyes open are within the 2 sigma range of normals and there is no significant difference from normals in these parameters even when the eyes are closed. Therefore these patients cannot be distinguished from normals by means of their platform recordings. (5) Two patients with posterior vermal and flocculo-nodular lesions were very unstable without preferred axis or frequency of instability. In contrast to the anterior lobe group the instability was characterized by the absence of intersegmental movements.

The reported direction of autokinesis for naive observers is not biased by gaze deviations of 22.5 deg of arc. However, instructions to expect either “inward” or “outward” movement produce reports of autokinetic movement that are progressively biased in the expected direction. Instructions to expect “more” or “less” movement resulted in a decrease in the reported duration of apparent movement for the “less” group but no change for the “more” group. Response bias is not considered to play a role in these results. The results are discussed in terms of fixational bias and selective attention mechanisms of autokinesis.

A stystematic neurological and electroencephalographical follow-up study in 344 head injured adults gave the following results: 1. 52% of all the hospitalized (mostly primarily amnesic) patients had a cerebral contusion. A contusion was assumed in cases with focal neurological signs (13%), amnesias of more than 8 hours (16%) and/or EEG-abnormalities lasting for more than 24 hours (49%). 2. Traumatic EEG-abnormalities were general slowing (43%) and foci (32%). In 40% of the cases with general slowing the slowing (greater than or equal to 1.5/sec) was within the alpha-frequency band and could only retrospectively be assed. 3. The EEG was invariably abnormal in cases with an amnesia exceeding 8 hours. If the amnesia exceeded 1 hour abnormalities were found in 73%. 4. Among the patients with contusion 6.5% had no amnesia, 48% less than 30 minutes and only 30% an amnesia for more than 8 hours. In 75% of the patients with concussion amnesia lasted less than one hour. 5. Skull fractures were mostly combined with contusion (74%). 6. Impaired drive, reduced ability to concentrate, memory deficits, headache and dizziness were significantly more frequent 6 months after contusion than after concussion. 7. 21% of the patients with traumatic dizziness (44%) had a labyrinthine contusion. 8. Among the contusions diagnosed with the aid of EEG recordings 58% would have been missed after exclusive neurological examination and 82% after application of the classical criteria used by surgeons and general practitioners.

The development of the visual contribution to postural stabilization has been tested using a large visual display rotating around the stationary subject's line of sight. This, in the adult, causes a marked optokinetic postural reaction with a shift of the body center of gravity toward the direction of pattern motion. Scalings of the reactions in children between 6 months and 16 years revealed three phases of development: (1) 6--12-month-old-babies show none or very little optokinetic disturbance of their newly acquired ability to sit. With the development of upright stance and gait, optokinetic influences become increasingly important. (2) Children between the age of 2--5 show a marked dependence of postural stability on vision. In them, the disturbing optokinetic stimulus leads to a marked ipsilateral postural deviation or irresistible fall. (3) From 5 to 15 years of age, visual effects on postural balance slowly decrease to their final strength in adulthood--moderate head and body tilt--in response to the rotating stimulus. It is concluded that the optokinetic loop participates rather late in the multisensory process of postural stabilization. The calibration of the three main loops, visual, vestibular, and proprioceptive, seems to be sequential and mutually interactive. Optimal functioning requires the continuous evaluation of the reafferent sensory consequences of self-generated body movements. Optokinetic destabilization of stance requires the maturity of opto-vestibulo-spinal pathways. Its clinical applicability as a maturity test, however, sofar seems limited.

The aim of the study was to identify the clinical and neurophysiological pattern of deficits in spinal arteriovenous malformations (AVM) to allow an early diagnosis which is the prerequisite for effective treatment by early surgery or embolization. Among 26 patients with myelographic signs of a spinal AVM, selective spinal angiography disclosed 20 cases with a dural AV-fistula (dAVF) and 6 patients with an intradural AV-malformation (iAVM). Although the main pathogenetic factor in both disorders may be different, clinical and neurophysiological findings proved to be of limited value in differential diagnosis. Clinical symptoms presented by the patients were a variable combination of lower motor neuron lesion, sphincter disturbance, sensory transverse lesion and partly additional signs of upper motor neuron involvement. Electromyography invariably showed an increased rate of polyphasia and frequently pathological spontaneous activity usually in several myotomes. Normal sensory conduction velocity of the sural nerve contrasted with almost regularly pathological SEP's after tibial nerve stimulation. The distribution if clinical and neurophysiological findings suggests rather widespread lesions of the lower cord and/or cauda equina, frequently at a lower level than the angiographically localized shunt. This suggests a vascular myelopathy on the basis of insufficient venous drainage at least for the frequent dural AV-anomaly.

In vivo activated T cells could be isolated from cerebrospinal fluid (CSF) of a patient suffering from chronic meningitis of unclear origin. Although the patient's skin reactivity to purified protein derivative (PPD) was negative, and peripheral T cells did not proliferate to this antigen in vitro, the majority of T cell clones from CSF specifically recognized PPD on either autologous or allogeneic HLA class II compatible macrophages. Remarkably, peripheral blood mononuclear cells potently suppressed the PPD-specific proliferative responses of healthy donors. The selective enrichment of oligoclonal IgG in the CSF but not in the patient's serum further indicated T and B cell responses lacking systemic feedback control. Analyses of a persisting immune stimulation in the CSF provide a potent diagnostic tool and may explain neurological complications as observed in a number of autoimmune diseases and chronic infections.

Movements of the arms (execution) in standing human subjects are preceded (preparation), accompanied, and followed (compensation) by muscular activity in postural trunk and leg muscles. Postural muscular activity compensates inertial forces acting on the body at the beginning and during arm movements and keeps the centre of gravity within the limits of stable upright standing. Standing normal subjects and patients performed bilateral arm elevations in response to an acoustic trigger. The beginning of EMG activity in the anterior deltoid muscle reflects the reaction time. Postural activity prior to the arm movement was observed in anterior tibialis, paraspinalis, and hamstring muscles. Compensatory muscular action occurred in the triceps surae. Motor preparation and compensation thus are an integral part of a motor programme. Muscles involved, latencies, and amount of EMG activity change with variations in the motor task (e.g. range of arm movement, changes in inertia of the arm, changes in initial body position). Reaction times and the pattern of preparatory and compensatory postural EMG activity were normal in most of the patients with Parkinson's disease. Reaction times were significantly increased in patients with cerebellar atrophy. The most prominent pathological feature in cerebellar patients was the inadequate temporal sequence of motor preparation and execution. Our results indicate that the basal ganglia play a minor role in motor preparation, whereas the cerebellum seems to coordinate the relative timing between motor preparation and execution.

Neurophysiological methods which allow to identify objectively lesions of the efferent cortico-spinal pathways in humans are with the exception of transcutaneous electrical stimulation of the motor cortex nor available. Long latency EMG responses from leg muscles are mediated by a "transcortical loop" and offer the possibility to detect in combination with sensory evoked potentials lesions both of the afferent proprioceptive and the efferent motor pathways. Subjects stood on a platform which was rotated toe-up (50 degrees/s, 4 degrees) around the axis of the ankle joint. This lead to two EMG responses of short- and medium latency in the stretched triceps surae muscle, and an EMG response of long latency (LL) from the antagonistic anterior tibial muscle. We investigated 135 patients with a spinal or cerebral lesion, detected by neuroradiological methods. We found a significant delay of LL in patients with spinal lesions and in patients with cerebral lesions on the affected side. A significant delay of LL could also be observed in patients with pure motor symptoms and normal latency of the cerebral potential (P 40) alone in the group of patients with spinal lesions revealed in about 45% a pathological result. The rate of pathological findings was about 65% when both methods (SEP and LL) were combined. The results indicate that the recording of LL is helpful to detect lesions of the efferent central pathways. In a follow-up study we investigated patients who underwent successful surgical treatment. We found a close correlation between the decrease in latencies of LL and the improvement of clinical signs.

Spontaneous eye movements and responses to visual and vestibular stimuli were recorded in 30 patients with pontine angle tumors (26 neurinomas, 2 meningeomas, 1 chosteatoma, 1 angioma). Pre- and postoperative recordings in most cases showed a bilateral dimunition of horizontal optokinetic nystagmus (OKN) that prevailed towards the side contralateral to the tumor. This is explained by a homolateral floccular lesion and cannot be the consequence of spontaneous nystagmus or asymmetrical gaze nystagmus. The predominance of a homolateral OKN-diminution often described in the literature was found in advanced cases or post-operatively as a sign of pontine reticular formation damage. The neighbourhood of the flocculus to the VIIIth nerve and animal experiments with floccular lesions causing a contralateral OKN diminution support out explanation. Additional arguments for damage of cerebellar oculomotor functions are the predominance of cogwheeled smooth pursuit and the occasional observation of hypermetric saccades, both toward the side of the tumor. Patients with very large tumors finally develop a complete disruption of OKN toward the homolateral side together with concomitant gaze paralysis.

The results of a systematic neurological and electro-encephalographical follow-up study in 344 head injured adults and 116 children were compared. The results show that posttraumatic EEG abnormalities lasting more than 24 hours, are equally frequent in children (53%) and in adults (49%). Mostly short lasting neurological signs of focal tissue damage are however significantly more frequent in children (30% vs. 13% and EEG-abnormalities (foci and general slowing) are on the average more pronounced. The recovery of EEG abnormalities follows the same pattern as in adults, occurs however faster among children. In both groups the normalization of general slowing precedes that of focal abnormalities only in 25% of the cases. Amnesias on the average last shorter in infants. Their duration seems of lesser significance for the judgement of the severity of the trauma in children than in adults. 6 months after the trauma children complain less frequently about headache, dizziness, or impaired memory and diminished ability to concentrate; emotional lability and impairement of drive, however, are more frequent than in adults. The results indicate an equal diagnostic and prognostic importance of systematic EEG studies (within 2 days, after 1 week and 6 month after the trauma) in both groups.

Doppler sonography of the extracranial arteries was done in 556 unselected patients (greater than 40 years) in a prophylactic study. 226 high risk patients with arterial occlusive leg disease (AOD) served as control group. Doppler sonography revealed stenoses or occlusions of the carotid, vertebral and (or) subclavian arteries in 9.17% of normal persons and in 38.05% of AOD patients. Medical treatment is available only for stenoses (not occlusions) of the carotid arteries. Thus the frequency of asymptomatic internal carotid stenoses--only stenoses of more than 50% lumen diminution can be detected--of 2.33% in the group of normal probands and of 17.2% in the patient group is the reference value and justification for use of Doppler sonography for prophylactic assessment. The atraumatic and safe method with a success rate of 2.33% is suitable particularly in increased risk factors (age, males, smoking, hypertension, diabetes). As a prophylactic investigation in patients with arterial occlusive disease Doppler sonography is mandatory before prospective operations.

The correlation between the severity of symptoms in myasthenia gravis (score) and the level of acetylcholine receptor-antibodies (ACHR-Ab) was studied in 24 patients treated with immunosuppressive therapy. This correlation was significant in every case regardless of whether or not thymectomy was performed in addition. It was demonstrated by means of a long-term follow up study, that a change in ACHR-Ab preceeds the corresponding change in score by 2-4 months in 80% of our patients. Measurements of ACHR-Ab ease the management of the therapy with immunosuppressants and make it safer. This is particularly true prior to and after termination of the treatment. A change in ACHR-Ab level by more than 20% indicates a change in score.

Fifty-two patients, most of whom had had daily headaches for years, were examined and treated. Among them there were 40 who originally had migraine, the others had vasomotor or post-contusional headaches. Average duration of the migraine was 21 years, of chronic headache 7.6 years. All patients had been taking analgesics of a mixed type regularly and for a long time, on average 35.6 tablets or suppositories weekly. All patients had taken more than three different drugs. After an observation period of 3-6 months for grading the headaches and registering the amount of drug intake, all patients were admitted to hospital when all analgesics were at once discontinued. Changing degrees of withdrawal symptoms were the rule: increased headaches, nausea, vomiting, tachycardia, sweating, sleep disorders, and in some also hallucinations and cerebral episodes. At the end of the hospital stay chronic headache had completely disappeared or markedly improved in 77% of patients. Even after an average of 16 months of subsequent observation, chronic headache continued to be significantly improved in 70% of patients. There was a significant reduction in frequency and intensity of attacks in the patients with originally typical migraine. Regular intake of analgesics of the mixed type induces chronic headaches. These are most commonly caused by ergotamine tartrate and aminophenol derivatives, while psychological and physical dependence on anti-migraine drugs is initiated and maintained by additional barbiturates, caffeine and codeine.

This study reports the case of a 19-year-old Turkish woman who was suffering from a cerebral abscess and granuloma formation caused by Candida albicans. The diagnosis of her illness was established by cytologic analysis of the cerebrospinal fluid. Combined application of amphotericin B and 5-fluorocytosine cured the patient's disorder. Its remission was documented over a period of 2 years by the use of computed tomography.

Postural stabilization in altered visual and vestibular conditions was investigated in humans subjected to fast transient disturbances and during sinusoidal movement of the standing support. Visual inputs were varied by applying stroboscopic illumination, stabilizing the visual surround in respect to head movements, inducing apparent body movement in pitch by continuously moving stripe patterns up or down and by eye closure. Static vestibular input was modified by bending the head forwards or backwards, or to the right or left shoulder (eyes closed). Neither biomechanical parameters of standing nor EMG responses of the anterior tibial and triceps surae muscles were modified by the different visual and vestibular conditions during fast transient (80 degrees/s) platform movements 4 degrees toe-up. Continuous regulation of upright stance during sinusoidal movements (1 Hz, 0.3 Hz), however, clearly depended on the different modifications of visual and vestibular inputs. Fast transient disturbances are easily compensated in a reflex-like manner independent of visual and vestibular feedback. Continuous regulation of upright posture during slow disturbances, however, clearly depends on the evaluation of afferent information from the visual, vestibular, and proprioceptive systems.

Correlation studies on patients with myasthenia gravis are reported in which clinical assessment of fatigue and neurophysiological findings are compared to blood levels of pyridostigmine. Measurements using a high-pressure liquid chromatography method (HPLC), give reproducible results. The levels of pyridostigmine in the serum or plasma of healthy controls and of patients show no essential differences. Components of coffee, tea, chocolate and cigarettes can markedly disturb the chromatography by adding additional peaks, so that interpretation becomes difficult or impossible. Blood levels can be measured approximately one hour after oral intake of 60 mg pyridostigmine. Concentrations rise for two to four hours and then decline exponentially. The half-life of pyridostigmine was between 156 and 210 minutes. Despite identical oral dosages, the concentration differed intraindividually and interindividually among patients. While the blood level does not reach its maximum value for 1-1 1/2 to 3 hours, the maximum clinical and neurophysiological effect of pyridostigmine appears 30-60 minutes after ingestion. Variable distribution of cholinesterase inhibitors over the different compartments (blood, synaptic region) is assumed to cause this temporal lag. If the total amount of pyridostigmine is divided into 4-5 doses, the concentration profiles over the course of a day are relatively stable. There is no significant correlation between the variations in blood level throughout one day, and changes in myasthenic symptomatology. Effects of pyridostigmine can be measured at levels as low as 5 ng/ml; at levels above 40 ng/ml further improvement can be detected only rarely. Blood levels were lower if corticosteroids were administered simultaneously; azathioprine had no influence on blood levels. Blood levels assays allow better differentiation of cholinergic and myasthenic crises and the identification of disturbed absorption and interactions with other medications.

The present study used recordings of visual potentials evoked by pattern reversal (VEPs) to investigate the central effects of three drugs used in migraine prophylaxis: the calcium channel blocker nifedipine, the beta-1-selective blocker metoprolol, and the nonselective beta adrenoreceptor blocker propranolol. The study involved 58 patients with common or classical migraine who were treated in a double-blind randomized study over a period of 7 months, while the effectiveness of prophylactic treatment was recorded in headache diaries that were subjected to time series analysis. VEPs were recorded at the beginning of a 2-month baseline period without treatment, after 4 months of treatment, and at the end of a 3-month washout period. At baseline, migraine patients had significantly higher VEP amplitudes and longer latencies than did a group of 87 healthy control subjects. Patients were separated by statistical analysis into responders and nonresponders to each prophylactic treatment. Nifedipine had no effects on the frequency, intensity, and duration of migraine attacks, nor on amplitude and latency of the VEPs. In contrast, the use of beta blockers resulted in a significant decrease in VEP amplitude, both in responders and nonresponders, whereas VEP latency remained unchanged. VEP amplitudes returned to the initial values at follow-up in the nonresponders, but stayed at lower levels in responders. Beta blockers thus appear to have a significant effect on the increased excitability of the visual system in patients with migraine, although their action is not directly related to their reduction of migraine frequency.