Biomedical subjects
Publications and source records attributed to H J Freund.
Wilson's disease (WD) was diagnosed on the basis of a liver biopsy, blood investigations and a radio copper test in a 60-year-old, neurologically normal female with uncharacteristic gastrointestinal complaints. Since this patient never developed symptoms indicative for WD this case suggests the possibility of a subclinical course of untreated WD.
Thirty-two patients with hemispheric stroke lesions of distinct cortical functional zones (premotor, precentral, parietal) or of striatocapsular or striatothalamic subcortical territories were scored at the acute and chronic stage for the following sensorimotor arm-hand functions: force, praxis, motor attention, sensation and dexterity. The selection criterion was that in spite of the wide variation of lesion sites all patients had hemiparesis as the presenting clinical sign. Analysis of the scores showed that most patients showed apraxia, motor neglect or disturbed sensation in addition to hemiparesis. The distribution and severity of these deficits varied, so that different lesion groups showed different patterns. The actual functional impairment of arm-hand function was determined by the combined effect of these different sensorimotor dysfunctions.
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One hundred HIV-positive individuals without clinically evident central nervous system (CNS) deficits entered this follow-up study and were examined clinically and with a well-defined motor test battery every 3 months over 2 years or until they decreased. They underwent magnetic resonance tomography once a year. None received any form of therapy at onset of the study. Three groups were analyzed: (A) patients without electrophysiologically detectable motor impairment (n = 23), (B) patients with electrophysiologically detectable motor impairment but no virostatic medication (n = 33), and (C) patients with motor deficits undergoing AZT treatment (n = 44) after study onset. Group A patients, although slightly deteriorating over time, had the best clinical and electrophysiological outcome compared to the other groups, whereas group B patients deteriorated markedly in both clinical and electrophysiological tests, even though the majority did not develop cerebral complications during the observation period. Those group C patients belonging to early CDC stages (II and III) improved electrophysiologically under AZT therapy, while 76% of the patients in more advanced stages (CDC IVA-D) died of cerebral AIDS manifestations. Four patients of this group, being alive at the end of the study, were completely demented. It is suggested that early detectable motor impairment predicts future cerebral involvement in AIDS. Late onset of virostatic treatment did not influence the clinical outcome.
In 4 male patients (age range 50-73 years) with unilateral motor hemineglect as a sequelae of circumscribed cerebral infarction, depressions of the regional cerebral glucose metabolism (rCMRGlu) were mapped to identify the metabolically affected cerebral structures. Motor neglect was defined according to Castaigne by lack of spontaneous and pain-induced motor activity on one side of the body in the absence of paresis, pyramidal signs, and sensory loss. The depressions of the rCMRGlu as determined by positron emission tomography (PET) were found to exceed the areas of structural damage but to be restricted to the affected cerebral hemisphere. Significant mean rCMRGlu depressions followed a focal pattern involving the premotor, prefrontal, parietal and cingulate cortex, as well as the thalamus. In correspondence to the lack of significant mean rCMRGlu depressions in primary sensorimotor cortex, basal ganglia, and cerebellum the cortico-spinal pathway was spared as indicated by preserved magnetic evoked motor potentials. Our data provide evidence suggesting that motor hemineglect is a disturbance in a cerebral network of higher order cortical areas subserving motor activity in the presence of an intact motor cortical output system.
We present the clinical, morphological and neuropathological findings in a 44-year-old male suffering from the acquired immunodeficiency syndrome (AIDS) (CDC stage IV C2) who presented with rapidly progressive right-side hemiparesis and developed hemianopia and aphasia. Scans showed multiple, not contrast-enhancing, not space-occupying echo-intensive lesions in T2-weighted MR-imaging. No hint for an opportunistic infection, necrotizing vasculitis or vascular disease was found. All therapeutic regimens failed and 8 weeks after onset of neurological symptoms the patient died because of cardiorespiratory arrest. Post-mortem examination excluded opportunistic infection, progressive multifocal leukoencephalopathy, lymphoma, vasculitis and ischemia of the brain. In the presence of an unusually high amount of HIV-infected macrophages at immunohistochemical examination, the overall pathological findings were atypical both for HIV encephalitis and HIV leukoencephalopathy. We describe a pathologically distinct new form of HIV associated encephalopathy.
We studied the cerebral activations related to restitution of hand function in five patients with first hemiplegic subcortical stroke due to ischaemic infarction in the area of the basal ganglia or thalamus. In two subjects, involvement of the cortico-spinal tract was demonstrated by magnetic evoked potentials. The subjects were requested to discriminate rectangular parallelepipeda of identical mass with their affected hands. Regional cerebral blood flow (rCBF) was measured with PET after intravenous bolus injection of [15O]butanol, at rest and during task execution. Evaluation of the rCBF changes was based on pixel-by-pixel t statistics of spatially standardized and averaged PET images and on a statistical distribution analysis of regions of interest in the individual subjects. For anatomical localization of the significant rCBF changes, a computerized brain atlas (Greitz et al. J Comput Assist Tomogr 1991; 15: 26-38) and a matching procedure that directly aligns individual PET and high resolution magnetic resonance images were used. The rCBF at rest and the task-induced rCBF changes varied from subject to subject, as did the residual neurological deficits at the time of PET scanning. In all subjects there were large activation areas in the motor and the sensory hand area contralateral to the affected hand. Poor performance of the task was correlated with a low rCBF in the contralateral sensorimotor cortex at rest and a bilateral activation of the primary sensorimotor cortex during task performance. The premotor cortex, ipsilateral and anterior cerebellum, contralateral to the affected hand, were also significantly activated. Further activations were observed in the contralateral premotor cortex, supplementary motor area and bilaterally in the posterior cingulate cortex, but were less consistent among the subjects. Our data suggest that recovery from hemiplegic stroke is associated with a marked reorganization of the cerebral activation patterns, including common and subject-specific activation sites. With respect to task-specific information processing a lower discrimination rate of objects compared with controls was associated with diminished activations in parietal lobe.
Using transcranial Doppler (TCD) ultrasonography in patients with high-grade (> or = 70%) internal carotid artery (ICA) stenosis, we examined the relation between the rate of TCD-detected silent microembolism of the ipsilateral middle cerebral artery and a history of recent (< 121 days) ischemic symptoms attributable to the diseased ICA. In the so-defined neurologically symptomatic group (n = 33 patients), silent microembolic events occurred in 27 subjects (overall mean rate, 14/h +/- 29). Among 56 neurologically asymptomatic patients matched for the degree of ICA stenosis, only nine showed such events (overall mean rate, 0.35/h +/- 1.4). Across all 89 patients studied, an individual microembolic event rate > or = 2/h had a positive predictive value of 0.88 for a history of recent symptoms. Our data suggest that TCD monitoring can provide reliable paraclinical evidence of "unstable ICA disease."
Protein C and protein S deficiencies increase the risk of venous thrombosis and pulmonary embolism, but their role in arterial thrombosis or embolism is controversial. We describe cerebral ischemia in two young women in a family with inherited deficiencies of both proteins C and S and provide evidence that a combined deficiency of proteins C and S may be a high risk factor for ischemic stroke in young adults.
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Myoclonic activity was analyzed in a 25-year-old male patient suffering from epilepsia partialis continua in his right finger and hand extensors and flexors. The involuntary tremorlike regular muscle jerks occurred at an average rate 7.7/s under resting conditions. Bursting frequency did not change during smooth ramp movements but increased up to 25/s during rapid extensions of the fingers. The EEG showed trains of sharp waves over the left temporoparietal and the midcentral regions but backaveraging did not yield reproducible jerk-related potentials. Somatosensory evoked potentials were not enhanced. It is suggested that the observed pattern of muscle jerks resulted from a spontaneous bursting behaviour of motor cortical neurones.
Small infarctions in the parietal cortex of Wistar rats were produced photochemically using the Rose Bengal technique. The infarctions evoked reproducible cortical lesions of about 2 mm diameter. In the surrounding brain tissue changes in electrophysiological responses occurred. Whereas in control animals a paired-pulse inhibition could be evoked all over the neocortex, in infarcted animals the paired-pulse inhibition was significantly reduced or even absent within an area extending up to 5 mm lateral from the lesion center. The changes in paired-pulse inhibition were already present on the first day and persisted at least up to 60 days after infarction. These functional changes may contribute to neurological deficits occurring after cerebral infarcts.
As a model for an integrated neuronal network based on the concept of modular units, we have investigated the occurrence of spontaneous activity and the formation of synaptic circuits in primary cultures of dissociated hippocampal neurons from the embryonic rat. Sodium-dependent action potentials (APs) could be elicited after 1 day in vitro (DIV), whereas spontaneous postsynaptic potentials (PSPs), "miniature" PSPs and APs appeared after 3-6 DIV. The number of cells with spontaneous APs and the rate of APs increased during development of the neuritic network. In addition to a stochastic spike interval distribution, pyramid-shaped neurons could be identified after 10-12 DIV, which fired preferentially at interspike intervals between 20-120 ms and 190-400 ms. This distinctive bimodal interspike interval pattern was sensitive to GABA-A antagonists. Simultaneous recordings of pairs of neurons demonstrated recurrent inhibitory, GABA-ergic synaptic circuits. In addition, a subpopulation of GABAergic neurons could be visualized by immunocytochemistry. These results are discussed in relation to the hypothesis that spontaneous firing of connected neurons is network-driven, based on synaptic "noise" and patterned by recurrent inhibition.
Modification of somatosensory processing depending on the behavioral setting was studied. Active alternating movements of the fingers, passive tactile stimuli to the hand, and active exploration of objects were performed during recording of somatosensory evoked potentials (SEPs). SEPs were elicited by compound electrical median nerve stimulation and electrical stimulation at detection threshold of cutaneous median nerve fascicles identified by microneurography. Electrical stimulation was not time-locked to the studied condition. In comparison with SEPs at rest there was attenuation of early cortical potentials up to 25 ms post-trigger in all nonresting conditions. In stimulation of the compound median nerve as well as of isolated cutaneous fascicles of a hand actively exploring an object there was an additional increased negativity, peaking at 28 ms. This facilitory effect was independent of attentional focusing and was absent during exploration using the ipsilateral, non-electrically stimulated hand. In patients with parietal lesions the facilitatory effect was diminished on the affected side. Spline interpolated brain maps at this latency based on 32-channel recordings in healthy volunteers showed a shift of local contralateral positive maximum from frontal to parietal during exploration, indicating enhancement of a tangential dipole. It is suggested that in conditions involving close sensorimotor interaction such as exploratory hand movements there is preactivation of a cortical area which is located in the central sulcus and receives cutaneous somatosensory inputs.
The initiation of coupled eye and arm movements was studied in six patients with mild cerebellar dysfunction and in six age-matched control subjects. The experimental paradigm consisted of 40 deg step-tracking elbow movements made under different feedback conditions. During tracking with the eyes only, saccadic latencies in patients were within normal limits. When patients were required to make coordinated eye and arm movements, however, eye movement onset was significantly delayed. In addition, removal of visual information about arm versus target position had a pronounced differential effect on movement latencies. When the target was extinguished for 3 s immediately following a step change in target position, both eye and arm onset times were further prolonged compared to movements made to continuously visible targets. When visual information concerning arm position was removed, onset times were reduced. Eye and arm latencies in control subjects were unaffected by changes in visual feedback. The results of this study clearly demonstrate that, in contrast to earlier reports of normal saccadic latencies associated with cerebellar dysfunction, initiation of both eye and arm movements is prolonged during coordinated visuomotor tracking thus supporting a coordinative role for the cerebellum during oculo-manual tracking tasks.
We report a case of Balo's concentric sclerosis diagnosed in vivo by characteristic MRI changes and stereotactic biopsy. Follow-up after 6 months of immunosuppressive treatment demonstrated virtually complete clinical remission, reduction of the white matter lesions on MRI and normalisation of regional cerebral glucose metabolism as assessed by positron emission tomography not only in white matter but also in the cerebral grey matter structures with input from the affected regions.
Thirty-three HIV-positive patients with clinical signs of dementia according to the 1991 AAN criteria underwent psychometric, electrophysiological and radiological examination and were compared with a group of normal healthy subjects and a cohort of clinically asymptomatic HIV-1-positive individuals of comparable education and social environment. Compared with the other groups, test performance was severely impaired in the demented patients. Results of motor testing and MRI revealed that subcortical structures were not exclusively affected, but most severely and early, thus characterizing the clinical feature in HIV-1-associated dementia. In demented patients a rapid deterioration was observed, leading to death within about 12 months on average, which is a markedly shorter survival time than described in the literature for non-demented HIV-1-positive individuals.
Bilateral damage of the medial temporal lobe system prevents the formation of new declarative memories but leaves intact knowledge that was acquired before damage. For motor learning, no structure has been identified that plays a comparable role for the consolidation of motor memories. The deficits of motor learning are focal and show a similar allocation to the various sensorimotor subsystems, as do the corresponding non-mnemonic functions. The involvement of sensorimotor circuitries changes during motor learning so that association areas are preferentially activated in the early stages, and cerebello- and striato-motor-cortical loops are preferentially activated in the late stages of motor learning. Recent neuroanatomical and neurophysiological findings on the effects of brain lesions in human and non-human primates are discussed.