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Biomedical subjects

J Dichgans

Publications and source records attributed to J Dichgans.

At least 19 recordsLinked to original sources

The coordination of posture and voluntary movement in patients with cerebellar dysfunction.

Postural adjustments associated with the task of rising on tiptoes were investigated in a reaction time paradigm in 10 normal subjects and 18 patients with cerebellar disorders. Cerebellar dysfunction was due to either degenerative cerebellar disease, tumor, or ischemia. Displacements of the center of foot pressure (CFP) were recorded. The task, accomplished by the triceps surae muscle (executional activity, mean latency of 411 ms), is mechanically effective only if the center of gravity has been shifted forward in advance. To this effect, a phasic burst of preparatory EMG activity in the tibialis anterior normally occurs at a mean latency of 163 ms, shifting the center of gravity forward. Shortly thereafter, activity of the quadriceps femoris (175 ms) extends the knee and aids the forward shift of the center of gravity. Different aspects of this motor sequence were disturbed in individual patients: Latencies of preparatory and executional activity were uncorrelated in 15 of the 18 patients. Executional (n = 16) or preparatory (n = 13) EMG activity was tonic instead of phasic. Latencies of either preparatory or executional EMG activities or both were prolonged (n = 10). The time interval between motor preparation and execution was increased (n = 9). The trial-to-trial variability of biomechanical parameters and EMG latency was increased. Preparatory EMG activity in the quadriceps was entirely missing (n = 9), resulting in knee bending at the unsuccessful attempt to rise on tiptoes. Patients who were most severely affected had no preparatory activity at all (n = 2), and therefore were unable to perform the task.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Pathophysiology of cerebellar ataxia.

Human and animal experiments performed recently have resulted in a more detailed understanding of limb movement and body posture disorders associated with cerebellar dysfunction. The delay in movement initiation can be explained by a delay in onset of phasic motor cortex neural discharge owing to decreased input from the cerebellar hemispheres. Disorders of movement termination (dysmetria), which can occur for movements at proximal and distal joints, result from disturbances of the timing and intensity of antagonist electromyographic (EMG) activity necessary to break the movement. Disorders in velocity and acceleration of limb movements result from muscular activity that is smaller in amplitude and more prolonged. The cerebellum is important for control of constant force but not for generation of maximal force. Dysdiadochokinesia is explained by a combination of the above mentioned mechanisms. During complex movements in three-dimensional space, the cerebellum contributes to timing between single components of a movement, scales the size of muscular action, and coordinates the sequence of agonists and antagonists. The basic structure of motor programs is not generated in the cerebellum. Hypotonia can be observed only in acute cerebellar lesions. Cerebellar tremor appears to result from a central mechanism, but is modulated or provoked through increased long-loop EMG responses. The common assumption that cerebellar ataxia of stance does not improve with visual feedback is true only of vestibulocerebellar lesions, not for ataxia resulting from atrophy of the anterior lobe of the cerebellum.

Cerebellar Ataxia

Neurophysiological evaluation of sensorimotor functions of the leg: comparison of evoked cortical potentials following electrical and mechanical stimulation, long-latency muscle responses, and transcranial magnetic stimulation.

Twenty-two patients with localized lesions of the central nervous system (unilateral cerebral ischaemia, cervical myelopathy, spinal tumour, familial spastic paraplegia) underwent neurophysiological evaluation of sensorimotor deficits of the leg. Functional methods using muscle stretch as stimulus, i.e. long-latency muscle responses and cortical potentials evoked by dorsiflection of the foot, were compared with transcranial magnetic stimulation and somatosensory evoked cortical potentials following electrical stimulation of the posterior tibial nerve. The functional neurophysiological methods yielded no diagnostic superiority with respect to the procedures using artificial (i.e. magnetic and electrical) stimulation. However, in most cases of missing compound motor action potentials following transcranial magnetic stimulation or missing electrically evoked cortical potentials, the long-latency muscle responses still allowed quantitative assessment of sensorimotor function.

Adult

Tonic pupil, areflexia, and segmental anhidrosis: two additional cases of Ross syndrome and review of the literature.

Two patients are described with the triad of tonic pupil, hyporeflexia and segmental anhidrosis (Ross syndrome). Only 18 cases of this syndrome have been reported in the literature so far. While tonic pupil and reduced sweating can be attributed to the affection of postganglionic cholinergic parasympathetic and sympathetic fibres projecting to the iris and sweat glands, respectively, the pathogenesis of diminished or lost tendon jerks remains obscure. To identify the characteristic clinical features, the previous cases of Ross syndrome are reviewed. Recent evidence of subclinical disturbances of sweating in most patients with Adie's syndrome, i.e. tonic pupil and areflexia, casts doubt on the nosological concept of Ross syndrome as a distinct clinical entity.

Adult

Ganglioside antibodies: a lack of diagnostic specificity and clinical utility?

Serum IgG and IgM antibodies to gangliosides GM1, GM2, GM3, AGM1, GD1a, GD1b and GT1b were determined in 210 patients with different degenerative and inflammatory disorders including motor neuron diseases, peripheral radiculopathies and neuropathies, multiple sclerosis and neuroborreliosis. No single disorder was associated specifically with ganglioside antibodies. No characteristic patterns of ganglioside antibodies were observed in any disease category. However, 32% of all patients had pathological antibody titres to at least one ganglioside. Four patients had pathological IgG and IgM titres for all gangliosides evaluated. They suffered from systemic lupus erythematosus [2], neuroborreliosis and schizophrenia, respectively. The results of this study indicate that the introduction of ganglioside antibody determination as a differential diagnostic test in clinical neurology is only helpful in a few patients with typical lower motor neuron syndromes.

Biomarkers

Automatic-voluntary dissociation: an unusual facial paresis in a patient with probable multiple sclerosis.

A patient with multiple sclerosis is described who presented with a unilateral loss of voluntary function of his lower face muscles. However, in an emotional situation, there was strong involuntary innervation of these muscles: automatic-voluntary dissociation. The subcortical afferents to the facial motor nucleus are discussed. It is hypothesized that cortical disinhibition of midbrain nuclei underlies the accentuated involuntary innervation.

Adult

Three-dimensional properties of human pursuit eye movements.

For any given location and velocity of a point target, there are infinitely many different eye velocities that the pursuit system could use to track the target perfectly. Three-dimensional recordings of eye position and velocity in 8 normal human subjects showed that the system chooses the unique tracking velocity that keeps eye position vectors (a particular mathematical representation of three-dimensional eye orientation) confined to a single plane, i.e. pursuit obeys Listing's law. One advantage of this strategy over other possible ones, such as choosing the smallest eye velocity compatible with perfect tracking, is that it permits continuous pursuit without accumulation of ocular torsion. For nonpoint targets, there is at most one eye velocity compatible with perfect retinal image stabilisation, and the optimal velocity may not fit Listing's law; we observed small but consistent deviations from the law during pursuit of rotating line targets.

Adult

Immunological abnormalities in the tears of multiple sclerosis patients.

IgG and IgM concentrations in tears of multiple sclerosis patients (n = 38) are increased compared to normal controls (n = 23). The occurrence of oligoclonal tear IgG bands (7.9%)--as determined by immunoblotting--did not differ between groups. Our findings suggest an altered reactivity of the secretory immune system in MS patients, but did not differ from findings in patients with eye affections or wearing hard contact lenses.

Adult

[Diagnosis and therapy of meningosis neoplastica].

Metastatic leptomeningeal disease occurs in 5-30% of patients with breast or lung cancer, malignant melanoma, non-Hodgkin's lymphoma, leukemia and primary malignant brain tumors. Intrathecal chemotherapy with methotrexate, cytarabine, or thiotepa combined with irradiation of the site of major involvement increases overall median survival from 1-2 months to 2-7 months. Clinical outcome is limited by progression of systemic or CNS disease and by the neurotoxic side effects of therapy, i.e. leukoencephalopathy. New immunotherapeutic strategies of intrathecal treatment may be effective and less toxic, but are not yet sufficiently defined and available. This review covers the current diagnostic and therapeutic features of metastatic leptomeningeal disease. Pragmatic therapeutic recommendations, based on available clinical knowledge are given with special consideration of the side effects of therapy.

Antineoplastic Combined Chemotherapy Protocols

Influence of an acoustic preparatory signal on postural reflexes of the distal leg muscles in humans.

In standing subjects the sudden displacement of a platform toe-up evokes a stabilizing postural response of the anterior tibial muscle (long-latency reflex). A preparatory signal (acoustic warning stimulus) preceding the postural perturbation by 1 s results in a significant decrease in latency of this long-latency response. There is no parallel modulation of the afferent cortical input in terms of evoked cerebral potentials following platform tilts toe-up nor of efferent cortico-spinal functions as evaluated by means of transcranial magnetic stimulation. Conceivable underlying mechanisms include faster intraspinal and/or intracortical processing of afferent input or switching to a shorter spinal reflex pathway.

Acoustic Stimulation

Cerebrospinal fluid interleukins, immunoglobulins, and fibronectin in neuroborreliosis.

Intrathecal synthesis of IgM and IgG, oligoclonal immunoglobulin bands, and the levels of fibronectin, soluble interleukin 2 receptor, interleukin 6, and tumor necrosis factor alpha were investigated with the use of enzyme-linked immunosorbent assay in 46 paired cerebrospinal fluid and serum samples from 32 patients with meningopolyradiculoneuritis due to Borrelia burgdorferi (Lyme borreliosis stage 2). Cerebrospinal fluid and serum interleukin 6, although not specific for neuroborreliosis, were good indicators of disease activity, while the serum soluble interleukin 2 receptor level was only mildly elevated. Tumor necrosis factor alpha was never detected in cerebrospinal fluid or serum specimens, and cerebrospinal fluid IgM, IgM index, and cerebrospinal fluid IgM/cerebrospinal fluid IgG ratios were significantly higher than in all other neuroimmunologic disorders evaluated and may be valuable diagnostic indicators for neuroborreliosis. The estimation of intrathecally synthesized IgG and IgM fractions for the differential diagnosis of neuroimmunologic disorders did not add to IgG and IgM index calculations.

Antibody Formation

Selective impairment of smooth-pursuit eye movements due to an ischemic lesion of the basal pons.

Voluntary and reflex-like eye movements were measured in a patient with an ischemic lesion of the right basal pons. Ipsilateral smooth-pursuit eye movements were predominantly impaired and interrupted by saccades. This profound smooth-pursuit deficit contrasted with only minor abnormalities of visually guided saccades and the vestibulo-ocular reflex. A selective disturbance of smooth-pursuit eye movements due to a lesion of the basal pons in this patient concurs with recent work in monkeys suggesting that smooth-pursuit eye movements are mediated by a parietooccipito-ponto-cerebellar pathway.

Brain Ischemia

Direction and amplitude precuing has no effect on automatic posture responses.

Automatic postural responses of leg muscles to the sudden displacement of standing support were investigated under four different conditions of information given to subjects in advance. Results from three groups of subjects were compared: 6 normal subjects, 10 patients with cerebellar disease, and 9 patients with Parkinson's disease. Specifically, each subject was provided with visual information about the direction and/or the amplitude of an upcoming platform tilt. For the control situation no advance information on the characteristics of platform tilt was provided. Neither the latencies nor the integrals of postural EMG-responses showed alterations with advance information. In contrast, in a control experiment in which 3 normal subjects had to perform large or small forward or backward voluntary movements of the body around the ankle joint, shorter onset-latencies of leg muscle EMG responses were observed with increasing complexity of the advance information. These results suggest that, unlike voluntary movements, postural responses to rapid surface tilts do not benefit from advance visual information on direction or amplitude of a postural disturbance.

Adult

Ergotamine, flunarizine and sumatriptan do not change cerebral blood flow velocity in normal subjects and migraneurs.

Changes in the diameter of extracranial and intracranial arteries resulting in changes in cerebral blood flow have previously been assumed to be the most important pathophysiological factor in migraine. To test this hypothesis 20 normal subjects, and three groups of patients (n = 29) with migraine were investigated by means of transcranial Doppler sonography. Blood flow velocities in the middle cerebral (MCA) and in basilar (BA) arteries were measured. Data from patients were obtained in the interval between migraine attacks, during migraine attacks and following treatment with either ergotamine (0.5 mg i.m.; n = 10); flunarizine, a calcium overload blocker (20 mg i.v.; n = 13); or a 5-HT1-like agonist (sumatriptan, 4 mg s.c.; n = 6). Ergotamine and sumatriptan are constrictors of cerebral arteries in animal experiments. The arithmetic mean of flow velocity in the BA was reduced in normal subjects (45 cm/s) as compared with patients with migraine measured in between attacks (53 cm/s). Mean flow velocity in MCA was not different in normals (72.5 cm/s) as compared with migraineurs (75 cm/s). Neither ergotamine nor the 5-HT1 agonist and flunarizine resulted in a significant change in blood flow velocity in MCA and BA. This was true irrespective of whether the drugs were given in the headache-free period, during a migraine attack or during the withdrawal phase of drug-induced headache. Ergotamine was effective in improving headache during migraine attacks and sumatriptan attenuated headache during drug withdrawal from chronic analgesic intake. These results indicate that the action of ergotamine and the 5-HT1-receptor agonist is probably not mediated by their vasoconstrictor action on cerebral arteries.

Adult

Superficial siderosis of the central nervous system. A 37-year follow-up of a case and review of the literature.

The course of a patient suffering from superficial siderosis of the central nervous system for 37 years is presented and diagnostic and therapeutic approaches are evaluated. The syndrome is clinically defined by slowly progressing deafness, cerebellar ataxia, myelopathy and neuropsychological deficits in combination with recurrent xanthochromia of the cerebrospinal fluid with siderophages. The diagnosis may be confirmed by computed tomography, which shows degeneration of the cerebellar vermis, and by magnetic resonance imaging, demonstrating iron deposits on the surface of brain, brain stem and spinal cord. Therapy should seek to identify and remove the source of bleeding, since pharmacotherapy with iron-depleting drugs is of limited effectiveness.

Brain Diseases

Neurosarcoidosis without systemic sarcoidosis.

Neurosarcoidosis is a well-recognised complication of systemic sarcoidosis but diagnosis may be difficult if there is no clear evidence of an extracerebral manifestation of the disease. We present the case of a 42-year-old woman with clinical features characteristic of cerebral sarcoidosis including tetraparesis, diabetes insipidus, diencephalic hyperphagia, personality changes, and memory loss. Diagnosis was supported by cerebrospinal fluid (CSF) findings and magnetic resonance imaging (MRI): CSF showed mild lymphocytic pleocytosis, intrathecal production of IgG without oligoclonal bands, and a raised level of lysozyme. MRI revealed multiple contrast-enhanced granulomas at the base of the brain with partial involvement of diencephalic and mesencephalic structures and parts of the spinal cord. There was no evidence of systemic manifestation of sarcoidosis. Administration of corticosteroids led to improvement of the symptoms.

Adult

Comparative analysis of cytokine patterns in immunological, infectious, and oncological neurological disorders.

Interleukins (IL) 1, 2, 4, 6 and soluble IL-2 receptor (sIL-2R), interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) were measured in CSF and serum from patients with relapsing-remitting and chronic multiple sclerosis, Guillain-Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, HIV infection, bacterial meningitis, viral encephalitis, meningeal carcinomatosis, hematologic meningeal malignancies, and disseminated melanoma. Our findings suggest that monitoring of disease activity in neuroimmunologic disorders by means of IL-1 beta, IL-2, sIL-2R, or IL-4 determination will not prove useful. IL-6, on the other hand, indicates relapse in multiple sclerosis and active disease in Guillain-Barré syndrome and meningeal carcinomatosis. High CSF TNF-alpha in metastatic melanoma and frequent detection in CSF of the multifunctional B-cell growth factor, IL-6 (27/30) and oligoclonal immunoglobulin bands (33%) in meningeal carcinomatosis confirm an intrathecal immune response in disseminated leptomeningeal neoplasia which might be amenable to therapeutic immunomodulation.

Cytokines

Influence of posture and voluntary background contraction upon compound muscle action potentials from anterior tibial and soleus muscle following transcranial magnetic stimulation.

Compound muscle action potentials (CMAPs) were recorded from anterior tibial (TA) and soleus (SOL) muscles following transcranial magnetic stimulation of motor cortex in 10 healthy subjects: (1) while standing upright without support, (2) while sitting, and (3) while lying supine. The results of this study demonstrate a significant influence of posture upon the amplitudes of CMAPs. Postural facilitation presented itself, firstly, in terms of a higher incidence of bilateral activation of distal leg muscles during stance and, secondly, as significant enhancement of the amplitude of CMAPs while standing as compared to lying supine. The onset latency, however, did not disclose a significant shortening during stance. To assess the effects of preinnervation subjects voluntarily adjusted the level of TA activity to 5%, 10% and 20% of maximum isometric force respectively before cortex stimulation. Voluntary background contraction resulted in a significant increase of amplitude of CMAPs but, in contrast to postural facilitation, concomitant with a significant decrease in onset latency. These results point to a somewhat different mechanism of facilitation during stance as compared to voluntary preinnervation. But it cannot be decided whether cortical mechanisms, different descending systems, the spinal circuitry or a combination of these factors is responsible for the observed effects.

Adult