Biomedical subjects
R J Seitz
Publications and source records attributed to R J Seitz.
Neurophysiology of the human supplementary motor area. Positron emission tomography.
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Epilepsy of the human supplementary motor area: positron emission tomography.
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Supplementary sensorimotor area seizure and ictal single-photon emission tomography.
Focal tonic seizures [supplementary motor seizures in the terminology of Penfield and Jasper (1) are often difficult to diagnose in terms of this chapter was undertaken to investigate whether ictal single-photon emission CT (SPECT) scanning could contribute to the diagnostic accuracy of this epileptic condition. In 15 patients (mean age, 21.3 years; ranges, 3 to 39 years) suffering from focal tonic seizures as the initial and most prominent seizure type, ictal SPECT scans were obtained after injection of 99mTc HMPAO within 30 seconds after clinical seizure onset. In 6 patients (40%; group I), ictal SPECT scans showed a focal hyperperused area concordant with results of other tests of the preoperative work-up (prolonged EEG/video monitoring, MRI, and positron emission tomography PET) using [18F]fluoro-2-deoxy-D-glucose (18FDG)] In 6 patients (group II), results of the ictal SPECT scans also showed findings of other tests of the clinical work-up. In 3 patients (group III), no ictal hyperperfusion could be observed. Results of the other presurgical tests in groups II and III were not sufficient to identify the seizure onset zone with the certainty needed for surgical resection. Ictal SPECT with HMPAO revealed confirmatory results in 40% of the patients with focal tonic seizures. In the remaining patients, results either were not congruent with other findings or did not show any change at all. This may have a twofold explanation: First (and probably most important), the interval between seizure onset and injection was too long considering the usually short duration of this seizure type, and second, the spatial resolution of SPECT imaging might not be sufficient to reveal a small seizure focus.
Large-scale plasticity of the human motor cortex.
The adult primate brain is capable of modifying rapidly the size of cortical receptive fields or motor output modules in response to altered synaptic input. We used positron emission tomography (PET) to map the regional cerebral blood flow changes related to voluntary finger movements in patients with tumours occupying the hand area of motor cortex. All patients showed activations solely outside the tumour. Compared with the unaffected side, the activations were shifted by 9-43 mm either along the mediolateral body representation of motor cortex or into premotor or parietal somatosensory cortex. These results provide evidence that slowly developing lesions can induce large-scale reorganization that is not confined to changes within the somatotopic body representation in motor cortex.
Stiff-person syndrome with anti-glutamic acid decarboxylase autoantibodies: complete remission of symptoms after intrathecal baclofen administration.
A female patient, aged 61 years, who developed a severe immobilizing stiff-person syndrome in conjunction with insulin-dependent diabetes mellitus, is described. In addition to the typical clinical symptoms, diagnosis was proven by the presence of autoantibodies against glutamic acid decarboxylase in serum and cerebrospinal fluid. Symptomatic treatment with continuous intrathecal application of baclofen administered by a subcutaneous pump resulted in rapid clinical improvement so that the patient became ambulatory. Intermittent withdrawal from intrathecal baclofen therapy led to complete remanifestation of stiff-person syndrome within 18 h; after re-introduction of intrathecal therapy stiffness disappeared completely within 48 h. The clinical course has been stable now for over 24 months and stiffness has completely disappeared. The effect of baclofen in this patient is discussed in the light of the suggested pathophysiological mechanisms in stiff-person syndromes.
Epileptic seizures triggered directly by focal transcranial magnetic stimulation.
Focal, secondarily generalizing, epileptic seizures were released by magnetic stimulation in a patient with focal epilepsy. The stimulation induced seizures had a similar clinical appearance to the patient's spontaneous seizures. They were released exclusively by an angulated "figure-of-8" coil which stimulates the brain more focally as compared to the commonly used flat round coil. The epileptic focus could be located in the left frontal cortex by electroencephalographic recordings, by magnetic resonance and by positron emission tomography imaging. Functional assessment of the motor system by transcranial magnetic stimulation (TMS) disclosed markedly prolonged electrical silence of contralesional electromyographic activity following the early excitation. This is the first EMG-documented demonstration of a focal motor seizure directly triggered by magnetic brain stimulation.
Representation and identity - convergence of brain research and mind-brain philosophy.
The localization or representation of mental abilities in the brain have always been considered as key questions for understanding the organization of the human nervous system. Particularly with the advent of modern electrophysiological and imaging techniques that provide maps of electromagnetic fields and metabolic processes on the living central nervous system, the representation theory is experiencing a scientific renaissance in neurology, but is only one theory, however, in the succession of a long philosophical tradition dealing with the possible identification of mental phenomena and brain processes. This dichotomy was formulated at the latest in the Cartesian dualism of res cogitans and res extensa of the mind-body problem. Nowadays philosophical discussion, on the contrary, is dominated by monistic concepts that attempt to explain the mental realm on an organic foundation in order not to succumb to the problem of a psychophysical dualism. Of these, the identity theory offers a philosophically plausible concept postulating that the identity of brain conditions and mental phenomena is based on organic foundations. In this theory, the efforts of brain research converge on the representations of mental phenomena in the human nervous system. In a comprehensive approach, both concepts could complement each other.
Subcortical origin of visuomotor apraxia.
Visuomotor apraxia (VMA) is a clinical syndrome characterized by a failure to make use of visual information when performing a target-directed movement. Visuomotor apraxia has traditionally been assumed to result from a disconnection of cortico-cortical fibres between visual and motor areas following occipito-parietal lesions. We describe a patient who developed a permanent contralesional and a temporary ipsilesional visuomotor apraxia as part of a complex neurological syndrome after a right [corrected] thalamic haemorrhage. MRI showed that the suprathalamic white matter was not involved but the most caudal fibres of the internal capsule appeared to be interrupted. To our knowledge this is the first case of a VMA with a lesion restricted to a deep subcortical area indicating that VMA can result from damage to subcortical projections rather than interruption of cortico-cortical fibres.
Palatal tremor of cortical origin presenting as epilepsia partialis continua.
Palatal tremor (PT) is frequently caused by brainstem lesions. The inferior olive plays a major role in the pathophysiologic mechanisms involved. We report a case of PT of cortical origin presenting as epilepsia partialis continua. EEG showed continuous left frontocentral epileptiform discharges and both single photon emission computed tomography (SPECT) and positron emission tomography (PET) showed focal hypoperfusion and hypometabolism in the corresponding location.
Successive roles of the cerebellum and premotor cortices in trajectorial learning.
The structures of the human brain engaged during learning of unilateral trajectorial hand movements were mapped by measurements of regional cerebral blood flow. Trajectorial movement velocity accelerated moderately after short-term training p < 0.025 and increased further after long-term training p < 0.01. During the early phase of learning there was a significant activation p < 0.001 of the ipsilateral dentate nucleus. By contrast, after overlearning the premotor cortical areas in both cerebral hemispheres were maximally activated p < 0.001, while the dentate nucleus was no longer activated. It is suggested that learning of new movement trajectories involves the cerebellum, while overlearned trajectorial movements engage the premotor cortex.
Deficient cerebral activation pattern in stroke recovery.
Specific cerebral activations induced by unilateral tactile discrimination of macrogeometric objects were identified in positron emission tomography images of regional cerebral blood flow in patients recovered from hemiplegic stroke and in healthy volunteers. Primary sensorimotor cortex, supplementary motor area, superior parietal lobule contralateral to moving hand, and premotor cortex on both sides were regularly activated in normals contrary to patients showing consistent activations only in the primary sensorimotor cortex. Furthermore, areas of activations in parietal association, premotor and midfrontal cortical areas were far less consistently activated in patients than in healthy subjects. These results demonstrated in correspondence to the clinical observations that the patients had regained their ability to move the fingers of the affected hand but remained impaired in tactile discrimination.
Pharmacokinetics and radiation dose of oxygen-15 labelled butanol in rCBF studies in humans.
In this positron emission tomography (PET) study in humans we determined the pharmacokinetics and radiation dose of oxygen-15 labelled butanol, a recently introduced tracer for regional cerebral blood flow (rCBF). This report includes a description of the automated preparation of 15O-butanol which allows repetitive activation studies, each 15 min apart. Dynamic rCBF studies were extended by prolonged measurements up to 15 min after injection over different organs such as brain, liver, kidneys and bladder. All measurements were done with a whole-body PET camera PC4096-15WB. Based on the pharmacokinetic data in 13 subjects the radiation doses to single organs were calculated according to MIRD pamphlet No. 11 and the effective dose defined by ICRP 60 as an indicator of radiation dose to the total body. The liver received the highest radiation dose of about 2.2 mGy per 1500 MBq of injected 15O-butanol, which is the typical amount of administered tracer in one rCBF measurement. The dose to the kidneys was 1.6 mGy, to the stomach 0.8 mGy, and to the brain 0.16 mGy. The effective dose was 0.54 mGy, which was similar to that of H2(15)O, but lower than the effective dose from C15O2 in amounts typically applied in human rCBF studies.
Dopamine D2 receptor binding and cerebral glucose metabolism recover after D-penicillamine-therapy in Wilson's disease.
Regional cerebral glucose metabolism (rCMRGlc) and dopamine D2 receptor binding were measured in a 31-year-old, severely affected, untreated patient with Wilson's disease of 3 years' duration using positron emission tomography and 18F-deoxyglucose and 18F-methylspiperone ([18F]MSP), respectively. There was a severe reduction of striatal and extrastriatal rCMRGlc as well as of striatal [18F]MSP accumulation rate. After 1 year of treatment with D-penicillamine, striatal and extrastriatal rCMRGlc and striatal [18F]MSP accumulation rate reached almost normal levels. It is hypothesized that recovery of motor functions due to copper trapping therapy was associated with an increase in basal ganglia activity and a re-expression or upregulation of dopamine D2 receptors.
Cerebral network underlying unilateral motor neglect: evidence from positron emission tomography.
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.
Dynamic changes of focal hypometabolism in relation to epileptic activity.
The interictal hypometabolism in patients with focal epilepsy is usually regarded as stationary. In this study we investigated to which extent the hypometabolism may depend on the activity of the epileptic focus. In focal penicillin-induced epilepsy in rats the epileptic focus is hypermetabolic. This focus is accompanied by hypometabolism in widespread areas of adjacent cerebral cortex. The experiments revealed that these metabolic alterations are transient. Data from a patient experiencing a focal seizure during PET scanning gave similar results. They showed that the transition from interictal to ictal activity was accompanied by the development of hypermetabolic epileptic focus and the dynamic enlargement of the surrounding hypometabolism. Both, the experimental and clinical data provide evidence that the cerebral hypometabolism may vary in size depending on the activity of the epileptic focus. It is hypothesized that in human PET studies the large interictal hypometabolism may prevent the identification of hyperactive interictal epileptic foci due to the partial volume effects resulting from the limited spatial resolution of PET cameras.
Tactile exploration of shape after subcortical ischaemic infarction studied with PET.
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.
Regional cerebral oxidative and total glucose consumption during rest and activation studied with positron emission tomography.
The relationship between regional oxidative and total rCMRglc in five healthy volunteers in activated and non-activated areas of the brain has been investigated with positron emission tomography (PET). The tracers [1-11C]-D-glucose and [2-18F]2-fluoro-2-deoxy-D-glucose were used. A previous study has shown that the former may be used to measure the rate of glucose oxidation while the latter tracer is used to measure the total rate of glucose consumption. Regional activation was performed (voluntary finger movements). Use of a computerized brain atlas enabled comparison between the regional oxidative and total rCMRglc in each volume element of the brain for the group of subjects. The values of total and oxidative rCMRglc, when calculated for each volume element of the brain and displayed in a scatter plot, were found to be symmetrically grouped around a straight line which passes close to the origin. The slope of this line varied between the subjects. This indicates that, on the average, the fraction of non-oxidative glucose utilization is constant within each subject, regardless of the value of rCMRglc and, further, that the fraction of non-oxidative glucose utilization varies between subjects. The total and oxidative CMRglc in the activated left hand area were 23.4 +/- 0.9% (mean +/- SEM) and 11.7 +/- 0.3%, respectively, higher than in the contralateral homologous non-activated area. Our interpretation of the difference is that regional activation increases the fraction of non-oxidative glucose consumption. This interpretation is supported by a previous PET study using [15O]O2, and by studies using MRS technique.