Dopaminergic dysfunction in midbrain dystonia: anatomoclinical study using 3-dimensional magnetic resonance imaging and fluorodopa F 18 positron emission tomography.

OBJECTIVE: To determine the role of damage to neuronal systems, especially the dopaminergic system, in patients with symptomatic dystonia and mesencephalic lesions. DESIGN: Stereotaxic magnetic resonance imaging analysis and positron emission tomography after the administration of fluorodopa F 18. PATIENTS: Of a group of 48 patients with unilateral dystonia following a stroke, 7 patients with a well-defined midbrain lesion were selected. RESULTS: All patients had unilateral dystonic posture of an upper extremity and cerebellar dysmetria or hypotonia. Cerebellar tremor was present in 1 patient. Two patients had resting and postural tremor, which showed a marked improvement with treatment with levodopa. In patients with dystonia only, dopaminergic lesions were mostly confined to the ventromesial mesencephalon and red nucleus area, including the substantia nigra and nigrostriatal and cerebellothalamic fibers. Dystonia was severe and did not resolve with time in patients with lesions involving the nigrostriatal pathway, and the degree of dopaminergic denervation revealed by positron emission tomography was correlated with the severity of dystonia. In patients with resting and postural tremor, lesions of the dopaminergic structures were larger and located more laterally and dorsally in the pars compacta, the perirubral and retrorubral areas, and extending to the central tegmental tract. CONCLUSIONS: Dopaminergic dysfunction plays a role in the occurrence and severity of midbrain dystonia, and additional lesions to dopaminergic neurons in the perirubral and retrorubral areas result in tremor that responds to levodopa treatment.

Spinocerebellar ataxia 3 and Machado-Joseph disease: clinical, molecular, and neuropathological features.

Patients with spinocerebellar ataxia 3 (SCA3) and Machado-Joseph disease (MJD) carry an expanded CAG repeat in the MJD1 gene. One hundred twenty families of different geographic origin with autosomal dominant cerebellar ataxia (ADCA) type I were tested. Thirty-four families (126 patients) carried an expanded CAG repeat. The expanded and the normal allele did not overlap and the repeat was unstable during transmission, with variation in the size of the CAG length ranging from -8 to +5 and a mean expansion of 0.86 repeats without differences according to the parental sex. There was a combined effect of the number of CAG repeats of the expanded and normal allele on the age at onset, which accounted for 70% of its variability. The length of the CAG repeat influenced the frequency of clinical signs associated with cerebellar ataxia, such as abnormal tendon reflexes or decreased vibration sense, whereas the interindividual variation of supranuclear ophthalmoplegia, sphincter and swallowing difficulties, and amyotrophy was mostly determined by different disease durations. We compared the clinical profile of 91 SCA3/MJD patients with 51 SCA1 and 32 SCA2 patients. There were striking differences between the SCA3/MJD and SCA2 but not with SCA1 groups of patients. Despite their clinical similarities, distinct neuropathological features were observed in 2 SCA3/MJD and 2 SCA1 patients.

The phenotype of "pure" autosomal dominant spastic paraplegia.

We studied 23 families with "pure" autosomal dominant spastic paraplegia. Examination of 142 at-risk individuals allowed identification of 70 patients, including 12 who were clinically affected but unaware of symptoms. The frequency of lower limb muscle weakness, decreased vibration sense, hyperreflexia in the upper limbs, and sphincter disturbances increased with the disease duration. The distribution of age at onset was unimodal, with a mean onset of 29 years (range, 1 to 68). The clinical manifestations of "early-onset" (< 29 years) and "late-onset" (> 29 years) patients were not significantly different. Age at onset varied as much within families as among families; anticipation and imprinting did not occur. No clinical criteria allowed differentiation among the families studied. Only linkage studies can provide accurate classification of this disease.

Unconscious processing in memory recall. A study of three amnesic patients.

The sudden resurgence of precise information some time after the failure of its recall (memory block) suggests the intervention of unconscious processes. In normal subjects the experimental demonstration of such processes meets with methodological snags. They are avoided in patients with a pure amnesic syndrome because retrograde amnesia produces many instances of missing memories, while anterograde amnesia prevents the patient from consciously thinking about it. Three patients with a pure amnesic syndrome were submitted to 4 interviews over 12 days on 3 topics concerning places and itineraries that were very familiar before the disease, and a shocking event of their life. Retrieved memories were compared to those of normal matched subjects. The results showed a dramatic increase for memories of places and itineraries over sessions, and the absence of improvement of autobiographical memories. These findings underline the role of the activation of unconscious processes in recall and the different status of semantic and episodic memory.

[Detection and peripheral or central localization of sensory pathway involvement of the lower limbs by somatosensory evoked potentials]. / Détection et localisation périphérique ou centrale des atteintes des voies sensitives par les potentiels évoqués somesthésiques des membres inférieurs.

In the presence of more or less atypical sensory or sensorimotor symptoms the questions that arise most frequently concern the authenticity of the disorders and the precise level of the lesion. In this study, somatosensory evoked potentials (SEPs) to stimulation of the tibial nerve at the ankle were recorded at different levels in 35 healthy subjects and 32 patients with sensory disorders. Recording electrodes were placed at the popliteal fossa (peripheral sensory nerve conduction velocity), at the T12-L1 level (medullary potential: N21) and at the vertex (P40 wave). The spine to cortex time interval was measured. A systematic study of evoked responses to median nerve stimulation was performed. The 32 patients were divided into 4 groups: Group I (3 cases) had slowed sensory conduction velocity (SCV), similar delay in N21 latency and normal N21-P40: peripheral neuropathy. Group II (4 cases) had normal SCV, delayed N21 latency and normal N21-P40: radicular or conus medullaris injury. Group III (19 cases) had normal SCV, normal N21 latency and lengthened N21-P40 interval. A study of responses to median nerve stimulation made it possible to discriminate between spinal and cortical or subcortical impairment. Group IV (6 cases) had abnormalities from any two of the three groups defined above. In 24 out of 32 patients (75 p. 100), further investigations (myelography, MRI, EMG) confirmed the localization determined by evoked responses. In the other 8 patients (25 p. 100) whose clinical picture suggested a medullary or radicular impairment, SEPs alone clearly revealed an injury. SEPs can distinctly show a spinal impairment and determine the choice of further investigations.

The clinical spectrum of alcoholic pellagra encephalopathy. A retrospective analysis of 22 cases studied pathologically.

A retrospective clinical study of 22 heavy alcohol drinkers is reported in which postmortem study showed diffuse chromatolysis of neurons identical to that found in neurological pellagra, associated in 13 cases with Marchiafava-Bignami disease and/or Wernicke-Korsakoff disease. The clinical features included confusion and/or clouding of consciousness, marked oppositional hypertonus ('gegenhalten') and myoclonus. Because of the frequent coexistence of other alcoholic encephalopathies in the same patient, alcoholic pellagra was often unrecognized. Fifteen patients received thiamine and pyridoxine therapy without niacin. It appeared to aggravate the neurological state or to trigger the development of alcoholic pellagra encephalopathy in 9 cases. The relationship between pellagra occurring during thiamine and pyridoxine therapy and 'nicotinic acid deficiency' is discussed. Multiple vitamin therapy should be given in the treatment of undiagnosed encephalopathies in alcoholic patients.

Chromatolysis in alcoholic encephalopathies. Pellagra-like changes in 22 cases.

In 22 patients with alcoholic encephalopathies, chromatolysis similar to that reported in endemic pellagra was found on postmortem examination. No gross macroscopic changes were seen in affected areas and only neurons were involved. The changes consisted of central chromatolysis, seen predominantly in the brainstem, especially in the pontine nuclei, where they were constant, and in the cerebellar dentate nuclei. Nuclei of cranial nerves (mainly the third, sixth, seventh and eighty), the reticular nuclei, arcuate nuclei and posterior horn cells, were also markedly affected. Changes were sometimes seen in the cerebral cortex, the interpeduncular nuclei, the central mesencephalic grey matter, the colliculi, the tenth and twelfth cranial nerve and perihypoglossal nuclei, the gracile and cuneate nuclei and anterior horn cells. This distribution was different from that reported in endemic and 'endogenous' pellagra or in isoniazid-induced pellagra encephalopathy. Central chromatolysis was the only pertinent finding of the CNS examination in 9 cases. In 8 cases, chromatolysis was associated with Marchiafava-Bignami encephalopathy, in 4 cases with Wernicke-Korsakoff encephalopathy, and in 1 other case with both. Mild degeneration of spinal cord tracts was seen in 3 cases. The chromatolysis of alcoholic pellagra did not appear to be a retrograde change related to axonal degeneration. Systemic examination showed liver changes in 15/16 cases. Treatment of these cases had not included niacin. No differences were found between cases given thiamine and pyridoxine and those which had not. Microscopic examination of the pons is essential in alcoholic encephalopathies.

Chronic localised encephalitis (Rasmussen's) in an adult with epilepsia partialis continua.

A 29 year old male presented with epileptic fits, progressive left sided focal seizures and epilepsia partialis continua, increasing left hemiparesis and mental slowing. Death occurred 2 years after the onset of the illness. Lesions were limited to the right cerebral hemisphere. Hypertrophic astrocytosis was diffuse throughout the gray and white matter but was more severe in the deep cortical layers and U fibres, where it was associated with vacuolar changes and capillary proliferation. Sparse perivascular lymphocytic cuffs, rod shaped microglia and microglial nodules were present. No inclusion bodies were found. These clinico-pathologic features were similar to the cases described by Rasmussen. Only five necropsy cases of this rare disease have been reported previously, all in children. The aetiology is unknown.

Effects of thalamic stroke on energy metabolism of the cerebral cortex. A positron tomography study in man.

Positron emission tomography was used to study the effects of unilateral vascular thalamic lesions on cortical oxygen and glucose utilization in 10 patients. There was significant ipsilateral cortex hypometabolism in 9 of the 10 patients, affecting the whole cortical mantle diffusely. The only patient spared was free of neuropsychological deficit at the time of positron emission tomography. In 4 patients, the magnitude of ipsilateral cortical hypometabolism was significantly less at a follow-up PET study, when neuropsychological function had improved. When taken together, the 14 studies showed a significant tendency for the hypometabolism to improve with time after clinical onset. These data suggest that the ipsilateral cortical hypometabolism results from damage to the thalamocortical connections and reflect either loss of nonspecific activating afferences or a degenerative deafferentation-deafferentation process, or both. Its links with the concept of diaschisis are suggested by its tendency to recover. A causal relationship between cortical hypometabolism and neuropsychological deficit, however, although strongly suggested, cannot be firmly established from the present data.

Human autonomy and the frontal lobes. Part I: Imitation and utilization behavior: a neuropsychological study of 75 patients.

A type of pathological behavior, imitation behavior (IB), is newly described. In this behavior patients imitate the examiner's gestures, although not instructed to do so. Patients explain that they thought they had to imitate the examiner. IB is the first stage of utilization behavior (UB). Neuropsychological examination of 40 patients with IB, of 35 with UB, and of 50 disease controls demonstrates the existence of a frontal syndrome and two determining features of such behavior: dependence on (1) the social and (2) the physical environments. Loss of intellectual control was also required for the occurrence of such behavior. UB and/or IB were present in 96% of the 29 patients with focal lesions of the frontal lobes. Computed tomographic scans in 26 of these patients showed involvement of the inferior half of the anterior part of one or both frontal lobes. IB and UB are interpreted as release of parietal lobe activities, resulting from impairment of frontal lobe inhibition.

[Cortical hypometabolism after a thalamic lesion in man: positron tomography study]. / Hypométabolisme cortical après lésion thalamique chez l'homme: étude par la tomographie a positons.

We used positron emission tomography to study the effects of unilateral vascular thalamic lesions on cortical oxygen or glucose utilisation in 10 patients. There was a significant ipsilateral cortex hypometabolism in 9 of the 10 patients, affecting diffusely the whole cortical mantle. The only patient spared was free of neuropsychological deficit at time of PET study. In 4 patients, the magnitude of ipsilateral cortical hypometabolism was significantly less at follow-up PET study, together with improved neuropsychological function. When plotted altogether, the 14 studies showed a significant tendency for the hypometabolism to improve with time elapsed since clinical onset. On the whole, these data suggest that the ipsilateral cortical hypometabolism reflects an essentially functional alteration an not only a degenerating process. This most likely indicates a cortical deafferentation due to loss of non-specific thalamo-cortical connections, i.e. a phenomenon akin to "diaschisis". However, a causal relationship between cortical hypometabolism and neuropsychological deficit cannot be firmly established from the present data.

Subcortical dementia. Frontal cortex hypometabolism detected by positron tomography in patients with progressive supranuclear palsy.

The dementia associated with progressive supranuclear palsy (PSP) is considered to be subcortical because the cerebral cortex, unlike the subcortical structures, is usually free from major neuropathological lesions; the characteristic symptoms point to a dysfunction of the prefrontal lobe. The regional cerebral metabolic rate of glucose (rCMR Glu) was studied by positron emission tomography and 18F-fluoro-2-deoxyglucose18FDG in 6 patients presumed to have PSP and was compared with values found in 8 control subjects of similar age. The results obtained showed a highly significant rCMR Glu decrease in the prefrontal cortex of our patients. The loss of several subcortical afferents to prefrontal cortex may be responsible for the frontal cortical hypometabolism present in PSP.

[Dementia and Parkinson's disease: biochemical and anatomo-clinical correlation]. / Démence et maladie de Parkinson: corrélations biochimiques et anatomo-cliniques.

Intellectual deterioration may be observed in the course of Parkinson's disease. Since it had been reported that central cholinergic systems degenerate in senile dementia and Alzheimer's disease, we measured the activity of choline acetyltransferase (C.A.T.) and the number of muscarinic receptors in various cortical regions of 12 control subjects and 20 patients and compared these biochemical results with clinical and neuropathological data concerning the patients. Thirteen of the parkinsonian patients showed signs of intellectual decline (moderate in 8, severe in 5) and neuropathological examination of the cortex revealed in 10 cases large number of Alzheimer type senile changes extending beyond the hippocampus. C.A.T. activity was decreased in the cerebral cortex in every patient. The decrease was greater in intellectually deteriorated patients and in the group with numerous senile changes in the cortex. The number of muscarinic receptors was increased in patients that had been treated with anticholinergic drugs until they died, but also in those who had not received these drugs, suggesting and underlying denervation hypersensitivity. In the caudate nucleus, however, neither C.A.T. activity nor muscarinic receptor number was altered, indicating that the cortical cholinergic lesion was specific. Although in most cases dementia in Parkinson's disease was of the Alzheimer type, the case of a demented parkinsonian patient in whom cortical C.A.T. activity was severely decreased, in spite of the absence of cortical histopathological evidence characteristic of Alzheimer's disease, suggests that a parkinsonian dementia different from the Alzheimer type also exists. In Parkinson's disease as in Alzheimer's disease the decrease in C.A.T. activity in the cerebral cortex results from degeneration of the cholinergic neurones in the nucleus of Meynert which projects to the cortex. Although the severity of intellectual deterioration seems in relationship with the extent of degeneration, this could already begin before intellectual impairment is apparent.

[Recurrent abortions and circulating anticoagulant. Relation to lupic disease: 6 cases]. / Avortements répétés et anticoagulant circulant. Rapports avec la maladie lupique: six observations.

Six women, aged 16 to 27 years old at the beginning of their illness suffered recurrent spontaneous abortion (two to eight episodes) and three of them had arteriolar venous thrombosis. These symptoms led to the finding of an antiprothrombinase type of circulating anticoagulant. In two cases, positive dissociated syphilitic serology was observed and all patients presented other haematological abnormalities: thrombocytopaenia and/or autoimmune haemolysis. The diagnosis of disseminated lupus erythematosis was established after an average period of 11 years (range 1 to 27 years) based on at least 4 of the ARA criteria (five out of six cases) and/or characteristic immunological abnormalities (five out of six cases). Thrombosis is more common in lupus when there are associated haematological abnormalities. It is probably directly related to the presence of circulating anticoagulant which inhibits the production and/or secretion of prostacyclin by the endothelial cells.