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Biomedical subjects

J Hildebrand

Publications and source records attributed to J Hildebrand.

At least 19 recordsLinked to original sources
PubMed1999

Cerebellar ataxia following whooping cough.

Bordetella pertussis (BP), the agent of whooping cough, has not been recognized so far as a cause of permanent cerebellar ataxia in human. We describe three patients who developed a disabling and permanent cerebellar syndrome soon after whooping cough. In two patients, diagnosis of BP infection was confirmed by culture of nasopharyngeal secretions. The infection occurred between the age of 13 and 15 years, with neurological symptoms beginning after a delay varying from 3 weeks to 3 months. In our three patients, the cerebellar syndrome was characterized by dysmetria of ocular saccades, scanning speech and ataxic gait. Brain MRI demonstrated a pancerebellar atrophy. The pathogenesis of this cerebellar degeneration is not established. Experimental studies have demonstrated that the cerebellum is particularly vulnerable to lymphocytosis-promoting factor (LPF), one of the exotoxins from BP. The mechanism of this toxicity might be a marked increase in the cellular levels of 3',5'cyclic guanosine monophosphate (cGMP). Since whooping cough is a bacterial exotoxin-mediated disease, this is the first report of a cerebellar syndrome triggered by a bacterial exotoxin.

Adult↗
PubMed1998

Different types of cerebellar hypometria associated with a distinct topography of the lesion in cerebellum.

We recorded ballistic wrist flexion movements in fifteen cerebellar patients exhibiting hypometria. The movement and the associated agonist and antagonist EMG activities were analysed. On the basis of the topography of the cerebellar lesion, our patients were divided into three groups. In the first group including five patients, lesions involved the efferent dentato-thalamo-cortical pathway and hypometria was associated with an imbalance between the rate of rise of the agonist EMG activity and the rate of rise of the antagonist EMG activity. In the three patients of group II, lesions were located at the level of the middle cerebellar peduncle, disrupting the crossed ponto-cerebellar projections. In these patients, the intensity of the agonist EMG activity was reduced and the duration of the antagonist EMG activity was increased. In the third group including seven patients presenting either a diffuse cerebellar atrophy or a stroke involving a large parenchymatous area, the agonist-antagonist EMG pattern showed a prolongation of the duration of the antagonist burst. Our results show that discrete mechanisms of cerebellar hypometria are associated with different anatomical lesions.

Adult↗
PubMed1998

Shift from hypermetria to hypometria in an aberrant recovery following cerebellar infarction.

Cerebellar hypermetria, a classical sign designating the overshoot when the patient attempts to reach rapidly an aimed target, is associated with an imbalance between timing and/or intensity of agonist and antagonist EMG activities. Recovery of hypermetria following a cerebellar ischemia or hemorrhage has been demonstrated to take place in a multistage process, but aberrant recovery following a cerebellar stroke has not been described previously. We report an 85-year-old woman presenting an abnormal recovery following a cerebellar infarction. We identified three successive stages. At stage 1, fast wrist flexion movements were severely hypermetric and associated with three EMG defects: a delayed onset latency of antagonist EMG activity, a reduction of intensity of the agonist EMG activity and a depression of intensity of antagonist EMG activity. At stage 2, movements were characterized by terminal oscillations around the target and the onset latency of the antagonist activity had returned to normal. At stage 3, movements were markedly hypometric, the intensity of the antagonist EMG activity had returned to normal, while the intensity of the agonist EMG activity remained abnormally low. This case illustrates an abnormal reprogramming of the EMG triphasic pattern, resulting in the shift from severe hypermetria to severe hypometria.

Aged↗
PubMed1998

Asymmetry of basal ganglia glucose metabolism and dopa responsiveness in parkinsonism.

We investigated, by positron emission tomography (PET) with [18F]fluoro-2-deoxy-d-glucose (FDG) (FDG-PET), brain glucose metabolism in 19 patients with parkinsonian features. We compared local pattern of FDG uptake and asymmetry indexes in patients with therapeutic response to levodopa (L-dopa) (group 1, presumed Parkinson's disease, n = 9) and patients without L-dopa therapeutic response (group 2, presumed striatonigral degeneration, n = 10). Limb dystonia was present in 11% of patients in group 1 and in 40% of patients in group 2. Asymmetry in basal ganglia metabolism was distributed differently in the two groups (analysis of variance, p < 0.04). In superior and inferior putamen, superior and middle caudate, ventral striatum, and inferior thalamus, relative reduction in metabolism on the side contralateral to predominant parkinsonian signs was associated with L-dopa unresponsiveness. On the contrary, in middle caudate, ventral striatum, and inferior thalamus, a relative increase in metabolism on the side contralateral to the predominant side, parkinsonian signs were found in L-dopa-responsive patients. Our FDG-PET study using simple statistical procedures demonstrates inverse asymmetry of basal ganglia glucose metabolism in parkinsonian patients grouped on the sole basis of L-dopa responsiveness.

Adult↗
PubMed1998

Response of recurrent glioblastoma and anaplastic astrocytoma to dibromodulcitol, BCNU and procarbazine--a phase-II study.

Twenty six (17 males) patients with glioblastoma (GBL), median age 55 years, median Karnofsky Index (KI) 70/100, and 11 patients (9 males) with anaplastic astrocytoma (AA), median age 56 years, median KI 70/100 were treated at recurrence with dibromodulcitol (DBD) 1400 mg/m2 on day 1, BCNU 150 mg/m2 on day 2, and procarbazine (PCZ) 150 mg/day on days 1 to 15. The course was repeated every 4 weeks, but was delayed or decreased by 25% according to hematological toxicity. Response to treatment was evaluated by the criteria of MacDonald et al. (J Clin Oncol 1990; 8: 1277-1280). All GBL-patients were followed until death. One patient with complete response (CR) survived one year, and 2 patients with partial response (PR) survived 1 and 3 years. Ten patients who stabilized (SD) survived 7.5 months, and 13 patients who progressed under chemotherapy had a median survival of 3.5 months. In AA-group 3 patients were alive at the time of the analyses. Six patients: 1 CR and 5 PR survived 6 to 40+ months. Two patients with SD survived 4 and 14 months. Three patients with progressive disease had a mean survived of less than 3 months. The response rate of 55% in AA was significantly higher (p = 0.011) than the 12% response rate seen in GBL. We conclude that the regimen tested appears particularly promising in AA. The results in GBL are comparable to those obtained with a single nitrosourea, despite an increased but reversible toxicity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Effects of TRH on ballistic wrist movements in cerebellar cortical atrophy: improvement of two genuine deficiencies but not of the major one.

Thyrotropin-releasing hormone (TRH) has been claimed to improve cerebellar ataxia in patients with idiopathic sporadic cerebellar cortical atrophy (CCA). We analysed the effects of intravenous administration of TRH (1 mg) in ballistic wrist flexions movements in 10 healthy subjects and in eight patients with CCA. The associated agonist and antagonist electromyographic (EMG) activities were recorded. In healthy subjects, TRH did modify neither the movement amplitudes, nor the intensity of the agonist and antagonist EMG activities. Before TRH administration, patients with CCA exhibited a hypermetria which was associated with a delayed onset of the antagonist activity. Moreover, the intensity of EMG activity in both the agonist and the antagonist muscles were reduced. After TRH, the hypermetria and the delayed onset latencies of the antagonist EMG activities were unchanged but the intensity of both the agonist and the antagonist EMG activities increased. TRH could increase the magnitude of agonist and antagonist EMG activities in patients with CCA by exerting an excitatory effect directly on motoneurons or by modulating at the supraspinal level the central commands to agonist and antagonist motoneuron pools. Copyright Rapid Science Ltd

Journal Article↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

[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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗