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Biomedical subjects

J Hildebrand

Publications and source records attributed to J Hildebrand.

At least 37 records · Page 2Linked to original sources

Kinematics of fast wrist movements in manic-depressive illness chronically treated with lithium carbonate.

Lithium salts have been shown to impair kinematics of fast voluntary movements during acute intoxication. The aim of the present study was to determine whether lithium carbonate affected the kinematics of fast movements in patients chronically treated and who did not exhibit signs of neurotoxicity. We analysed fast wrist flexion movements in 6 healthy subjects, in 5 patients presenting a manic-depressive illness without treatment, and in 8 patients receiving lithium carbonate for a manic-depressive disease. The mean duration of treatment was 3.9 +/- 4.1 years, the mean daily dose 837 +/- 341 mg and the mean serum level 0.95 +/- 0.15 mEq/l. Although mean movement amplitudes were similar in the 3 groups, the variability of fast movements was increased in patients receiving lithium salts. The ratio of maximum to average velocities (Vm/Vave) was significantly higher in patients treated, and their movements were temporally asymmetrical, with a ratio of acceleration duration divided by deceleration duration being lower than in the 2 other groups. These kinematic abnormalities show that a chronic treatment with lithium salts is associated with an impairment of the cerebellar control of fast single-joint movements.

Acceleration↗

Ataxia induced by small amounts of alcohol.

A patient is described who exhibited cerebellar ataxia after drinking small amounts of alcohol. Intake of 5 g alcohol induced a gaze evoked nystagmus, a scanning speech, a body sway after eye closure, and bilateral postural leg tremor. Kinematic and EMG analysis of fast wrist movements showed normal movements before and marked hypermetria after alcohol intake. Dysmetria was due to abnormal programming of antagonist muscle activity.

Alcohol Drinking↗

[Lesions of ponto-cerebellar and olivo-cerebellar afferents demonstrated by neurophysiologic analysis].

We describe a 52-year-old woman presenting a 2-year history of limb clumsiness and gait difficulties, characterized by progressive worsening. Neurological examination revealed cerebellar intention tremor, cerebellar dysmetria of all 4 limbs and ataxic gait. However, brain MRI was normal. Analysis of fast wrist flexion movements demonstrated hypometric movements, with decreased intensities of agonist EMG activities and increased durations of antagonist EMG activities. Such EMG abnormalities have been demonstrated in patients presenting lesions of the middle cerebellar peduncle, affecting the crossed cerebellopontine projections. Moreover, adaptation motor learning during a pinch task (isometric force) showed a severe inability to adapt motor programming, indicating a disruption of cerebellolivary and cerebellopontine afferent systems. We suggest that our patient presented an exceptional brainstem syndrome involving the function of cerebellar inflow tracts. Such electrophysiological findings are not encountered in patients presenting a cerebellar cortical degeneration or cerebellovlivopontine atrophy, and might have important implications in the treatment of cerebellar ataxia in the future.

Afferent Pathways↗

Analysis of single-joint rapid movements in patients with sporadic olivopontocerebellar atrophy.

Patients with pure cerebellar cortical atrophy (CCA) present isolated cerebellar signs, whereas patients with sporadic olivopontocerebellar atrophy (sOPCA) present various combinations of cerebellar and extracerebellar signs. However, the differential diagnosis between these two forms of cerebellar degeneration is often a challenge for the clinician. Therefore, any test helping in this differential diagnosis might have a potential clinical interest. In this study, our goal was to investigate the adaptation to increased inertia in patients with sOPCA exhibiting combined cerebellar and pyramidal signs, during the performance of fast wrist flexions. We found that these patients exhibited a hypermetria which remained unchanged after addition of inertia, because they were unable to increase neither their agonist activity (launching force), nor their antagonist activity (braking force). This contrasts with our previous findings in patients with CCA. In these latter, the hypermetria worsened when the inertial load of the hand increased because those patients were able to increase their agonist activity, but not their antagonist activity. The adaptation to inertia might thus help to differentiate CCA and sOPCA.

Adult↗

Dissociation in the neural control of single-joint and multi-joint movements in the thalamic ataxia syndrome.

We report a patient presenting with a right thalamic ataxia syndrome following a hemorrhage located in the left lateral and posterior thalamus. We investigated the fast goal-directed movements of the wrists (single-joint movements) and the fast pointing movements in the upper limbs (multi-joint movements). On the right side, single-joint movements were markedly hypermetric and characterized by an asymmetry in kinematics, an abnormality of ballistic movements which is considered to be a fundamental cerebellar disorder. By contrast, rapid multi-joint movements were only very slightly impaired. These results suggest that ballistic movements of the wrist are under the strong influence of the cerebello-thalamo-cortical pathway, while rapid pointing multi-joint movements in upper limb are mostly influenced by another pathway emerging from the lateral cerebellum, possibly the dentato-rubral or the dentato-reticular projections in the brainstem. The roles of these neuroanatomical pathways in the control of fast single-joint and multi-joint movements are discussed.

Ataxia↗

Cerebellar spongiform degeneration induced by acute lithium intoxication in the rat.

Cerebellar syndrome has been described after acute lithium intoxication in human. Neuropathological studies have demonstrated neuronal loss and spongiosis in the cerebellum. We describe an animal model of acute lithium-induced cerebellar degeneration. Five hours following administration of lithium chloride (250 mg/kg, i.p.), the cerebellar white matter of seven rats out 14 exhibited extensive spongiform changes. Microdialysis study in the rat cerebellar cortex demonstrated basal concentrations of dopamine (DA), hydroxy-3-methoxyphenylacetic acid (HVA) and 5-hydroxy-3-indolacetic acid (5-HIAA). These metabolites were unaffected by acute lithium intoxication suggesting that the cerebellar toxicity is not due to a modification of dopaminergic or serotoninergic neurotransmission.

Acute Disease↗

Glucocorticoid-induced long-term remission in primary cerebral lymphoma: case report and review of the literature.

We report a 25-year old immunocompetent woman with a high grade primary non-Hodgkin's lymphoma of the central nervous system (PNHL-CNS) in whom the administration of dexamethasone alone during three months produced a complete clinical and radiological response lasting over four years. If complete remission of PNHL-CNS induced by glucocorticoids are well known, the opportunity to observe glucocorticoid-induced remission for a long period of time without radio- and chemotherapy is rare. Only nine other cases of PNHL-CNS with complete remission induced by glucocorticoids lasting from 6 to 60 months, were found in the literature and are summarized here. Duration of glucocorticoids therapeutic effect in PNHL-CNS is probably underestimated. Glucocorticoids cannot be recommended as sole initial treatment for PNHL-CNS. However, we suggest standard therapies to be delayed in those patients responding completely to glucocorticoids where radio- and chemotherapy should be contraindicated (kidney, liver, bone marrow failure, pregnancy).

Adult↗

Treatment of tumours.

Technical progress made in neuroradiology, and focal external and internal radiation therapy, have allowed the development of a series of local therapeutic modalities both in primary and in metastatic brain tumours. Eligibility criteria and results obtained with these new techniques are compared. Experimental studies with implications for radiation therapy, particularly boron neutron capture therapy, and for chemotherapy are reviewed. The possible use of chemotherapy as first-line treatment in non-Hodgkins lymphomas of central nervous system is stressed.

Animals↗

Central nervous system lesions associated with Crohn's disease.

Central nervous system vasculitis is an exceptional extraintestinal manifestation of Crohn's disease. Reported here are 2 cases, highlighting the difficulty of differential-diagnosis with multiple sclerosis and stressing the importance of early immuno-suppressive therapy.

Adult↗

Intracerebral transplantation of fetal ventral mesencephalon for patients with advanced Parkinson's disease. Methodology and 6-month to 1-year follow-up in 3 patients.

In order to launch a new transplantation program for Parkinson's disease (PD), we evaluated the safety and efficacy of fetal ventral mesencephalic grafts in 3 patients with advanced PD. Inclusion criteria and clinical evaluation followed strictly the Core Assessment Program for Intracerebral Transplantation. The transplantation procedure was based on the technique previously described by the groups in Lund (Sweden) and Créteil (France). The putamen contralateral to the site of predominant symptoms was unilaterally grafted in all patients. Magnetic resonance (MR)-based stereotactic guidance with multiplanar correlation was used to define 3 implantation trajectories in the precommissural, commissural, and postcommissural putamen. Fetal ventral mesencephalon was prepared from 6- to 8-week-old human embryos obtained from same-day abortions. Under general anesthesia, 8 deposits of 3 microliters of the fetal tissue were placed 1 mm apart along each implantation trajectory using a customized microsyringe and needle attached to the stereotactic frame. The patients recovered uneventfully from the neurosurgical procedure. Early postoperative MR clearly showed the implantation trajectories reaching the putamen in all patients. The follow-up period was of 12, 9 and 6 months, for each of the 3 patients, respectively. Clinical changes appeared between 3 and 6 months after transplantation and consisted of an increase in the 'on' periods and in quantitative bilateral improvement in the motor timed tests. There was an improvement of the Unified Parkinson's Disease Rating Scale score and an improvement of rigidity. Tremor was unchanged, and there was a slight and transient increase in dyskinesias. Neuropsychological follow-up revealed slight frontal alterations in 2 patients. Positron emission tomography demonstrated an increase of 18F-fluorodopa uptake in the grafted site. Adverse events include a reversible Cushing syndrome secondary to immunosuppression in 1 patient and a transient episode of confusion in another. The results of this study, designed as a prerequisite for a wider transplantation program, are in accordance with those previously reported by others and show that, using standardized neurosurgical techniques and methods of evaluation, transplantation is a reproducible and safe therapeutic approach which provides clinical benefits to patients with advanced PD.

Brain Tissue Transplantation↗

Management of malignant brain tumors.

This review is made up of two parts. The first section describes techniques and methods used in the treatment of malignant brain tumors, stressing the most recent developments. The second part reviews the therapeutic modalities in malignant gliomas, where an attempt is made to consider separately glioblastomas, anaplastic astrocytomas and oligodendrogliomas, low-grade glioma, medulloblastoma, primary brain lymphoma, and brain metastases. A decision making algorithm is suggested for each tumor type.

Algorithms↗

Audiogenic startle reflex in acute hemiplegia.

The generators of the audiogenic startle reflex (ASR) are located in the bulbopontine reticular formation. We studied the influence of acute vascular supratentorial lesions on ASR. Ten patients with hemiplegia due to hemispheric cerebral infarct were studied within 5 days of stroke onset. ASR and magnetic cortical stimulation were performed the same day. A muscle response to magnetic stimulation was not elicited over the plegic side in any patient. In four of seven patients, ASR was enhanced over the plegic side. We suggest that enhanced ASR is due to the loss of a predominantly inhibitory hemispheric drive on ASR generators.

Acoustic Stimulation↗

Microdialysis-HPLC for plasma levodopa and metabolites monitoring in parkinsonian patients.

We used in vitro microdialysis-HPLC to determine L-3,4-dihydroxyphenylalanine (L-DOPA) and its metabolites in plasma of patients with advanced Parkinson disease. Blood samples and clinical evaluations were obtained 0, 30, 60, 90, 120, and 150 min after oral administration of carbidopa/L-DOPA (25/100 mg, 12.5/125 mg, and 50/200 mg). In vitro recoveries for L-DOPA and metabolites ranged from 22% to 36%. Linear correlation was found between metabolite concentrations in the dialysate and in the surrounding medium. There was a significant positive correlation between L-DOPA dose and plasma concentration of L-DOPA and homovanillic acid (P < 0.04). Clinical response was maximum 60 min after L-DOPA administration. Threshold L-DOPA plasma concentration averaged 7.74 +/- 3.3 mumol/L. Motor effect is longer with the highest L-DOPA peak concentration (P < 0.01). Microdialysis-HPLC is readily applicable, reproducible, and allows monitoring of plasma L-DOPA and metabolites in parkinsonian patients.

Aged↗

Regional methionine and glucose uptake in high-grade gliomas: a comparative study on PET-guided stereotactic biopsy.

UNLABELLED: Gliomas are regionally heterogeneous tumors. The local relationship between histologic features and radiotracer uptake evaluated by PET should therefore influence analysis and interpretation of PET results on gliomas. This study explored this local relationship as a result of PET guidance of stereotactic biopsies. METHODS: Local histology was confronted to the regional uptake of 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) and 11C-methionine (11C-MET) in 14 patients with high-grade glioma diagnosed during a procedure of PET-guided stereotactic biopsies. We analyzed the uptake of both tracers in regions of interest centered on the stereotactic coordinates of 93 biopsy samples. RESULTS: A semiquantitative analysis revealed a significant regional correlation between 11C-MET and 18F-FDG uptakes. Uptake of both tracers was significantly higher on the site of tumor samples showing anaplastic changes than in the rest of the tumor. Presence of necrosis in anaplastic areas of the tumor significantly reduced the uptake of 11C-MET. CONCLUSION: PET with 11C-MET and 18F-FDG may help to evaluate, in vivo, the metabolic heterogeneity of human gliomas. Anaplasia is a factor of increased uptake of both tracers, but microscopic necrosis in anaplastic areas influences their uptake differently. This finding probably relates to the differences in tracer uptake by non-neoplastic components of necrotic tumors. These results underline the complementary role of 18F-FDG and 11C-MET for the study of brain tumors and favors their use for stereotactic PET guidance of diagnostic or therapeutic procedures.

Adult↗