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Biomedical subjects

E Broussolle

Publications and source records attributed to E Broussolle.

At least 55 records · Page 3Linked to original sources

Analogical transfer is effective in a serial reaction time task in Parkinson's disease: evidence for a dissociable form of sequence learning.

Several studies of procedural learning in Parkinson's disease (PD) have demonstrated that these patients are impaired with respect to age-matched control subjects. In order to examine more closely the specific impairment, we considered three dimensions along which a procedural learning task could vary. These are: (1) implicit vs explicit learning, (2) instance vs rule learning, and (3) learning with internal vs external error correction. We consider two hypotheses that could explain the impairments observed in PD for different types of explicit motor learning: (H1) an impairment related to the acquisition of rules vs specific instances, and (H2) an impairment in learning when no explicit error feedback is provided. In order to examine the condition of rule learning with external error feedback, we developed a modified version of the serial reaction time (SRT) protocol that tests analogical transfer in sequence learning (ATSL). Reaction times are measured for responses to visual stimuli that appear in several different repeating sequences. While these isomorphic sequences are different, they share a common rule. Verbatim learning of a sequence would result in negative transfer from one sequence to a different one, while rule learning would result in positive transfer. Parkinson's patients and age-matched controls demonstrate significant acquisition and positive transfer of the rule between sequences. Our results demonstrate that PD patients are capable of learning and transferring rule or schema-based representations in an explicit learning format, and that this form of learning may be functionally distinct from learning mechanisms that rely on representations of the verbatim or statistical structure of sequences.

Adult↗

[Incidence and clinical profile of familial forms of Parkinson's disease. A study of 428 index-cases from a department of neurology].

Although the cause of Parkinson's disease remains to be determined, several lines of evidence favor the role of a genetic factor. We therefore studied a series of 428 index-cases of Parkinson's disease that were referred to our Department of Neurology between 1986 and 1993, with the aim to identify secondary family cases. Index-cases were divided into 2 groups. In groups A (279 cases), a retrospective analysis of patients records was performed. In group B (149 cases), a prospective study was carried out by 1992, which allowed a more complete investigation of family history. In group A, 31/279 index-cases (11.1 p. 100) had secondary familial cases of Parkinson's disease. This percentage increased up to 22.8 p. 100 among index-cases in group B (34/149 cases). In most instances, only one secondary case was detected, and very few proponents had 2, or 3 other family cases. No large family with numerous Parkinson's disease cases was disclosed. Age at onset of disease was similar in group A between sporadic and familial index-cases, whereas in group B age at onset was earlier index-cases with positive family history as compared to those without (53.9 +/- 10.4 years versus 59.7 +/- 12.1 years respectively). This may be due to the different sizes of groups A and B, whereas clinical profile analysis did not differentiate index-cases with positive family history from those without family history (sporadic cases). An anticipation of age at onset of illness of 13.9 +/- 12.2 years was found in 9 of the 15 index-cases from group B with first degree parental vertical inheritance, where clinical data were available for the second family case. These findings about age at onset may be at least partly explained by a more accurate estimation of age at onset in index-cases than that in secondary family cases. Further analysis on the possible mode of transmission of the disease among familial cases was consistent with the implication of a genetic factor in the ethiopathogenesis of the disease, with a mendelian autosomal dominant inheritence with reduced penetrance.

Disease Transmission, Infectious↗

[Leber "plus" disease: optic neuropathy, parkinsonian syndrome and supranuclear ophthalmoplegia].

A 34-year-old right handed man presented with a bilateral subacute optical neuropathy associated with cervical dystonia, parkinsonism and supranuclear ophtalmoplegia. Magnetic resonance imaging showed in T2 increased intensity of signal in the dorsal mesencephalum and pons as well as in dorsal part of striata. The 3,460 mutation of mitochondrial DNA was found in a blood sample. This observation adds to the variability of presentation of Leber's "plus".

Adult↗

Slowly progressive anarthria with late anterior opercular syndrome: a variant form of frontal cortical atrophy syndromes.

We describe eight patients with slowly progressive speech production deficit combining speech apraxia, dysarthria, dysprosody and orofacial apraxia, and initially no other deficit in other language and non-language neuropsychological domains. Long-term follow-up (6-10 years) in 4 cases showed an evolution to muteness, bilateral suprabulbar paresis with automatic-voluntary dissociation and frontal lobe cognitive slowing without generalised intellectual deterioration. Most disabled patients presented with an anterior opercular syndrome (Foix-Chavany-Marie syndrome), and pyramidal or extrapyramidal signs. CT and MRI findings disclosed asymmetric (left > right) progressive cortical atrophy of the frontal lobes predominating in the posterior inferior frontal region, notably the operculum. SPECT and PET revealed a decreased cerebral blood flow and metabolism, prominent in the left posterior-inferior frontal gyrus and premotor cortex, extending bilaterally in the most advanced cases. Pathological study of two cases showed non-specific neuronal loss, gliosis, and spongiosis of superficial cortical layers, mainly confined to the frontal lobes, with no significant abnormalities in the basal ganglia, thalamus, cerebellum, brain stem (except severe neuronal loss in the substantia nigra in one case), and spinal cord. We propose to call this peculiar syndrome Slowly Progressive Anarthria (SPA), based on its specific clinical presentation, and its metabolic and pathological correlates. SPA represents another clinical expression of focal cortical degeneration syndromes, that may overlap with other similar syndromes, specially primary progressive aphasia and the various frontal lobe dementias.

Aged↗

Effect of parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation.

In monkeys rendered parkinsonian, lesions and electrical stimulation of the subthalamic nucleus reduce all major motor disturbances. The effect of electrical stimulation of the subthalamic nucleus was assessed in three patients with disabling akinetic-rigid Parkinson's disease and severe motor fluctuations. Quadripolar electrodes connected to a pulse generator were implanted in the subthalamic nuclei on both sides. Patients were evaluated with the unified Parkinson's disease rating scale and timed motor tests. 3 months after surgery, activities of daily living scores had improved by 58-88% and motor scores by 42-84%. This improvement was maintained for up to 8 months in the first patient operated upon. One patient was confused for 2 weeks after surgery, and another developed neuropsychological impairment related to a thalamic infarction which improved over 3 months. In one patient, stimulation could induce ballism that was stopped by reduction of stimulation. This is the first demonstration in human beings of the part played by the subthalamic nuclei in the pathophysiology of Parkinson's disease.

Electric Stimulation Therapy↗

Magnetic resonance imaging evidence of decreased putamenal iron content in idiopathic Parkinson's disease.

OBJECTIVE: To determine the changes in basal ganglia iron content associated with various stages of idiopathic Parkinson's disease. DESIGN: Prospective magnetic resonance imaging study using a 2-T magnet. SETTING: Ambulatory care referral center. PATIENTS AND PARTICIPANTS: Forty-five patients suffering from levodopa-responsive Parkinson's disease and 45 age-matched controls. MAIN OUTCOME MEASURES: The T2 relaxation time calculated in various regions of the basal ganglia, the duration of Parkinson's disease, and the age of subjects. RESULTS: Patients with Parkinson's disease exhibited significantly decreased T2 relaxation time in the pars compacta of the substantia nigra compared with controls (P < .01), regardless of disease duration. Patients with a duration of illness above 10 years (n = 12) exhibited significantly increased T2 relaxation time in the anterior and posterior putamen (P < .005 and P < .01, respectively) and in the pallidum (P < .05) compared with age-matched controls. Putamental T2 relaxation time positively correlated with disease duration (P < .05). CONCLUSION: These results suggest that more complex brain iron changes than those previously reported are associated with idiopathic Parkinson's disease, including increased nigral iron content and decreased putamenal and pallidal iron concentration in patients with a duration of illness above 10 years.

Adult↗

Bilateral subthalamic nucleus stimulation for severe Parkinson's disease.

Subthalamic nucleus (STN) lesions or high-frequency stimulations could improve parkinsonian symptoms in monkeys treated by MPTP. We have applied the procedure of chronic stimulation to the STN in severely disabled parkinsonian patients. This article presents the case of the first patient operated on bilaterally. Bilateral STN stimulation has greatly improved akinesia and rigidity. The benefit was maintained < or = 15 months after surgery. Unilateral stimulation induced motor effects mainly in contralateral limbs. Further studies are needed to evaluate the value of this procedure in the treatment of Parkinson's disease.

Antiparkinson Agents↗

Motor imagery of a lateralized sequential task is asymmetrically slowed in hemi-Parkinson's patients.

We examined seven right-handed, asymmetrical (right side affected) Parkinson's disease patients and seven age-matched controls in a manual finger sequencing test using left and right hands in vision, no vision, and motor imagery conditions. All patients displayed motor asymmetry, favoring the left hand. They also displayed motor imagery asymmetry, mentally simulating movement more slowly with their right affected hand than with their left hand. Additionally, impairment in mental hand rotation correlated significantly with the imagery asymmetry. These data support two related hypotheses: (a) Motor sequence imagery and execution share common neural structures. (b) The frontostriatal system is among these shared structures.

Adult↗

Apomorphine in patients with Parkinson's disease.

We present a review of the recent literature and personal experience with apomorphine in patients with Parkinson's disease. Apomorphine is a potent D1 and D2 dopaminergic agonist. It has a rapid and short duration effect after subcutaneous administration at doses ranging from 15 to 180 micrograms/kg. Plasma maximal concentration is reached in 8-16 minutes, with a plasma half life of 34-70 minutes. Bioavailability is close to 100%. Repeated injections in patients show post-stimulative hyposensitivity. Apomorphine test appears very useful for the differential diagnosis between idiopathic Parkinson's disease and other Parkinson plus syndromes, and as a predictive test for dopaminergic responsiveness. Appropriate doses are able to alleviate akinesia, rigidity and tremor. Recent therapeutic trials have demonstrated the high interest of intermittent multiple subcutaneous apomorphine injections to cut the "off" motor phases in fluctuating parkinsonian patients under chronic levodopa treatment. In some cases, continuous apomorphine subcutaneous infusion with a portable pump may be required, particularly when levodopa treatment is temporarily interrupted, as after abdominal surgery. During long-term treatment, the apomorphine dose able to relieve akinesia remains stable. Peripheral side effects such as nausea and hypotension may be prevented by the co-administration of domperidone, a peripheral dopaminergic antagonist. Cutaneous fibrous nodules and psychiatric symptoms may occur, but usually at high dosages with continuous infusion. Local allergic effects have limited the use of other routes of administration, such as intranasal, sublingual, and rectal routes. Apomorphine is also used as a pharmacological tool for clinical research with the aim of a better understanding of the pathophysiology of Parkinson's disease.

Antiparkinson Agents↗

[Striato-pallido-dentate calcifications and acquired facial atrophy].

A family with two siblings presenting cerebral calcifications is reported. The sister was suffering from action tremor since the age of 10. The disease worsened by the age of 39. When aged 42, she was unable to walk and had severe rigidity and intellectual deterioration. She died at 43. The brother had mild debility. Action tremor started at the age of 14, without significant aggravation when seen at the age of 30. In both cases, brain CT scan showed calcifications of the dentate nuclei and cortical atrophy with ventricular enlargement. In addition, the sister had bilateral putaminal and pallidal calcifications. The other family members were unaffected and had normal CT scans. The nosology and the pathophysiology of this family report are discussed, particularly regarding the late occurrence of facial atrophy, reminiscent of the Cole-Engmann syndrome (Dyskeratosis Congenita).

Adult↗

Relief of akinesia by apomorphine and cerebral metabolic changes in Parkinson's disease.

The cerebral metabolic rate of glucose was measured in 14 Parkinson's disease patients with severe on-off fluctuations. Two positron emission tomography (PET) scans with [18F]fluorodeoxyglucose were performed, one after a challenge of subcutaneous apomorphine at a dose able to relieve akinesia within 15 min and the other with the vehicle. Apomorphine reduced glucose utilization by 4-6% in the lenticular nuclei and the occipital cortex and by 6-9% in the thalamic nuclei, but this effect was not statistically significant. Thus, central stimulation of dopamine receptors by apomorphine in advanced Parkinson's disease is not associated with cerebral metabolic changes as assessed by PET. Despite a dramatic improvement of the motor state, the global neuronal activity in the striatum and its downstream projections remains stable, suggesting an equilibrium between excitatory and inhibitory dopaminergic activities.

Aged↗

Pharmacokinetics of apomorphine in parkinsonian patients.

Apomorphine, a dopamine agonist, has been used efficiently in parkinsonian patients to treat severe levodopa-induced on-off phenomenon. Motor improvement has been obtained both with continuous subcutaneous (SC) infusions, and multiple SC injections. So as to assist in the understanding of the clinical results, we studied the peripheral pharmacokinetics of apomorphine in 20 patients after intravenous (IV) or SC injections in the anterior abdominal wall and in the thigh at various doses, or SC infusion. Plasma apomorphine levels were measured by high-performance liquid chromatography with electrochemical detection. After an SC injection in the abdominal wall, the Tmax was brief (16 +/- 11 min) the drug was rapidly cleared from the plasma and had a short plasma half-life (69.7 +/- 25.8 min). The AUC was similar following SC and IV injections, suggesting that apomorphine was completely absorbed from subcutaneous tissue. Inter-subject variability in drug absorption was large. We noticed a trend towards a more complete absorption following injection in the abdominal wall rather than in the thigh. In patients chronically treated by continuous SC infusion, the apparent plasma half-life was five times longer than that following SC or IV injections. These pharmacokinetic data may explain the rapid onset and brief duration of clinical effects, and the usefulness of individual titration for intermittent SC apomorphine injections, and the smoother motor response obtained with continuous SC infusions.

Abdomen↗

[Treatment of Wilson's disease with zinc. 5 cases].

Zinc treatment of Wilson's disease was introduced by Schouwink en 1961 and is still uncommon in France. We evaluated the effectiveness and safety of zinc in 5 patients with Wilson's disease aged from 19 to 40 years. There were three neurological, one hepatic and one asymptomatic cases. Zinc was administered in doses of 120 to 272 mg/day, alone in 3 cases and combined with D-penicillamine in 2 cases. After 1 to 7 years of zinc therapy, our experience is consistent with data from recent literature and provides further evidence of zinc effectiveness. Zinc may be prescribed as first treatment in most patients, including asymptomatic cases. The only exception concerns patients with severe symptoms in whom it is recommended to combine zinc with D-penicillamine during the early phase of treatment for more rapid effectiveness. Because of its safety, zinc is particularly indicated in cases of intolerance to D-penicillamine and trien.

Adult↗