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Biomedical subjects

Y Agid

Publications and source records attributed to Y Agid.

At least 19 recordsLinked to original sources
PubMed2006

Dihydropteridine reductase deficiency: levodopa's long-term effectiveness without dyskinesia.

We report an adult patient lacking endogenous synthesis of monoamines (dopamine, serotonin, and catecholamines) due to a severe dihydropteridine reductase (DHPR) deficiency. With levodopa and 5-hydroxytryptophan (5HTP) supplementation, the patient exhibited moderate mental retardation, acute episodes of parkinsonism, and episodes of depression. Despite the use of levodopa from age 3 months, he exhibited no dyskinesia or dopaminergic cell loss as suggested by normal PET imaging of the dopamine transporter.

5-Hydroxytryptophan↗
PubMed2006

Neurosurgery at an earlier stage of Parkinson disease: a randomized, controlled trial.

BACKGROUND: Stimulation of the subthalamic nucleus is an effective treatment for advanced Parkinson disease (PD) and is currently performed after a mean disease duration of 14 years, when severe motor complications have resulted in marked loss of quality of life. We examined whether surgery at an early stage would maintain quality of life as well as improve motor function. METHODS: Twenty patients with PD of short duration (time elapsed since first symptom +/- SD: 6.8 +/- 1.0 years) with mild to moderate motor signs (Unified Parkinson's Disease Rating Scale III "off" medication: 29 +/- 12) who responded well to levodopa treatment were included in pairs, matched for age, duration and severity of disease, and impairment in socioprofessional functioning. Patients were prospectively randomized to undergo bilateral subthalamic nucleus stimulation (n = 10) or receive optimized medical treatment (n = 10). Parkinsonian motor scores, quality of life, cognition, and psychiatric morbidity were assessed at inclusion and at 6, 12, and 18 months after randomization. RESULTS: Quality of life was improved by 24% in surgical and 0% in nonsurgical patients (p < 0.05). After 18 months, the severity of parkinsonian motor signs "off" medication, levodopa-induced motor complications, and daily levodopa dose were reduced by 69%, 83%, and 57% in operated patients and increased by 29%, 15%, and 12% in the group with medical treatment only (p < 0.001). Adverse events were mild or transient, and overall psychiatric morbidity and anxiety improved in the surgical group. CONCLUSIONS: Subthalamic nucleus stimulation should be considered a therapeutic option early in the course of Parkinson disease.

Activities of Daily Living↗
PubMed2006

Neurosurgery in Parkinson disease: a distressed mind in a repaired body?

OBJECTIVE: To prospectively evaluate the impact of subthalamic nucleus (STN) stimulation on social adjustment in patients with Parkinson disease (PD). METHODS: Before and 18 to 24 months after bilateral STN stimulation, the authors assessed 29 patients with PD for motor disability, cognition (Mattis dementia rating scale, frontal score), psychiatric morbidity (Mini-5.0.0, MADRS, BAS), quality of life (PDQ-39), social adjustment (Social Adjustment Scale), and psychological status using unstructured in-depth interviews. RESULTS: Despite marked improvement in parkinsonian motor disability, the absence of significant changes in cognitive status, and improvement of activities of daily living and quality of life by the end of the study, social adjustment did not improve. Several kinds of problems with social adjustment were observed, affecting the patients' perception of themselves and their body, marital situation, and professional life. Marital conflicts occurred in 17/24 couples. Only 9 out of 16 patients who had a professional activity before the operation went back to work after surgery. CONCLUSION: After STN stimulation, patients experienced difficulties in their relations with themselves, their spouses, their families, and their socio-professional environment. The authors suggest a multidisciplinary psychosocial preparation and follow-up to help patients and their entourage cope with the sudden changes in their existence following successful neurosurgery.

Cognition Disorders↗
PubMed2006

Parkinson's disease with camptocormia.

BACKGROUND: Camptocormia is defined as an abnormal flexion of the trunk that appears when standing or walking and disappears in the supine position. The origin of the disorder is unknown, but it is usually attributed either to a primary or a secondary paravertebral muscle myopathy or a motor neurone disorder. Camptocormia is also observed in a minority of patients with parkinsonism. OBJECTIVE: To characterise the clinical and electrophysiological features of camptocormia and parkinsonian symptoms in patients with Parkinson's disease and camptocormia compared with patients with Parkinson's disease without camptocormia. METHODS: Patients with parkinsonism and camptocormia (excluding patients with multiple system atrophy) prospectively underwent a multidisciplinary clinical (neurological, neuropsychological, psychological, rheumatological) and neurophysiological (electromyogram, ocular movement recording) examination and were compared with age-matched patients with Parkinson's disease without camptocormia. RESULTS: The camptocormia developed after 8.5 (SD 5.3) years of parkinsonism, responded poorly to levodopa treatment (20%) and displayed features consistent with axial dystonia. Patients with camptocormia were characterised by prominent levodopa-unresponsive axial symptoms (ie, axial rigidity, gait disorder and postural instability), along with a tendency for greater error in the antisaccade paradigm. CONCLUSION: We suggest that (1) the salient features of parkinsonism observed in patients with camptocormia are likely to represent a specific form of Parkinson's disease and camptocormia is an axial dystonia and (2) both camptocormia and parkinsonism in these patients might result from additional, non-dopaminergic neuronal dysfunction in the basal ganglia.

Aged↗
PubMed2006

Preservation of cognitive function in dystonia treated by pallidal stimulation.

OBJECTIVE: To assess the effects of bilateral pallidal deep brain stimulation (DBS) on mood and cognitive performance in patients with dystonia before surgery (at baseline, while patients received their usual treatment) and 12 months postoperatively (while patients received neurostimulation and their medications) in a multicenter prospective study. METHODS: Twenty-two patients with primary generalized dystonia were evaluated with tests focused on executive functions. The authors considered the patients' severe disability and selected the following tests: Raven Progressive Matrices 38, Similarities and Arithmetic subtests of the Wechsler Adult Intelligence Scale-R, Grober and Buschke, Wisconsin Card Sorting Test (WCST), verbal fluency, Trail Making Test, and the Beck Depression Inventory. Median age at surgery was 30 years (range = 14 to 54 years), median duration of disease was 18.5 years (range = 4 to 37 years). RESULTS: Before surgery, no patients showed cognitive decline or depression. The surgical procedure appeared to be benign cognitively. One year after surgery, free recall improved. There was a significant reduction in the number of errors in the WCST. No behavioral or mood changes were found. CONCLUSIONS: Bilateral pallidal stimulation has a good benefit-to-risk ratio as it did not negatively affect cognitive performance and mood in primary dystonia, while a significant motor improvement was obtained. Moreover, a significant mild improvement in executive functions was observed, which may have been related either to the surgical treatment or to the marked decrease in anticholinergic drugs.

Adolescent↗
PubMed2006

Neurosurgery in Parkinson's disease: the doctor is happy, the patient less so?

Despite the overall excellent outcome of neurosurgery in patients with Parkinson's disease, there is often a contrast between the improvement in motor disability and the difficulties of patients to reintegrate a normal life. In this study, the personal, familial and professional difficulties experienced by patients two years after bilateral high frequency stimulation of the subthalamic nucleus were carefully analyzed. To avoid such socio-familial maladjustment, we strongly suggest taking into consideration the patients' psychological and social context before the operation and during the post-operative follow-up.

Deep Brain Stimulation↗
PubMed2005

Bilateral deep brain stimulation in Parkinson's disease: a multicentre study with 4 years follow-up.

Deep brain stimulation (DBS) is associated with significant improvement of motor complications in patients with severe Parkinson's disease after some 6-12 months of treatment. Long-term results in a large number of patients have been reported only from a single study centre. We report 69 Parkinson's disease patients treated with bilateral DBS of the subthalamic nucleus (STN, n = 49) or globus pallidus internus (GPi, n = 20) included in a multicentre study. Patients were assessed preoperatively and at 1 year and 3-4 years after surgery. The primary outcome measure was the change in the 'off' medication score of the Unified Parkinson's Disease Rating Scale motor part (UPDRS-III) at 3-4 years. Stimulation of the STN or GPi induced a significant improvement (50 and 39%; P < 0.0001) of the 'off' medication UPDRS-III score at 3-4 years with respect to baseline. Stimulation improved cardinal features and activities of daily living (ADL) (P < 0.0001 and P < 0.02 for STN and GPi, respectively) and prolonged the 'on' time spent with good mobility without dyskinesias (P < 0.00001). Daily dosage of levodopa was significantly reduced (35%) in the STN-treated group only (P < 0.001). Comparison of the improvement induced by stimulation at 1 year with 3-4 years showed a significant worsening in the 'on' medication motor states of the UPDRS-III, ADL and gait in both STN and GPi groups, and speech and postural stability in the STN-treated group. Adverse events (AEs) included cognitive decline, speech difficulty, instability, gait disorders and depression. These were more common in patients treated with DBS of the STN. No patient abandoned treatment as a result of these side effects. This experience, which represents the first multicentre study assessing the long-term efficacy of either STN or GPi stimulation, shows a significant and substantial clinically important therapeutic benefit for at least 3-4 years in a large cohort of patients with severe Parkinson's disease.

Activities of Daily Living↗
PubMed2005

Treatment of end-of-dose wearing-off in parkinson's disease: stalevo (levodopa/carbidopa/entacapone) and levodopa/DDCI given in combination with Comtess/Comtan (entacapone) provide equivalent improvements in symptom control superior to that of traditional levodopa/DDCI treatment.

The aim of this study was to evaluate the efficacy of the new optimised levodopa, Stalevo (levodopa, carbidopa and entacapone) in patients with Parkinson's disease experiencing end-of-dose wearing-off. Treatment with Stalevo was compared to treatment with traditional immediate-release levodopa and dopa-decarboxylase inhibitor (DDCI) formulations along with adjunct entacapone (Comtess/Comtan). A European, open, parallel-group, active treatment-controlled phase IIIb study evaluating 176 patients randomised to switch from their current regimen of levodopa/DDCI to either an equivalent dose of Stalevo or levodopa/DDCI plus entacapone. After 6 weeks, treatments were assessed using the Clinical Global Impression of Change, the Unified Parkinson's Disease Rating Scale and a Motor Fluctuations Questionnaire. Over 70% of patients in both the Stalevo and adjunct entacapone arms felt that they were clinically improved and over 80% experienced a reduction in fluctuations. Although there was no significant difference between Stalevo and levodopa/DDCI plus entacapone with regard to motor improvement and side effects, 81% of patients stated that they preferred treatment with Stalevo compared with taking two separate tablets (i.e. levodopa/DDCI and entacapone). Stalevo was well tolerated and safe when substituted for levodopa DDCI preparations.

Aged↗
PubMed2005

Parkinson disease, brain volumes, and subthalamic nucleus stimulation.

BACKGROUND: High-frequency stimulation of the subthalamic nucleus (STN) is an effective treatment for advanced Parkinson disease (PD). The clinical and preoperative predictive factors of the best postoperative outcome have been identified. Radiologic predictive factors were investigated. METHODS: Forty patients with PD underwent surgery for bilateral STN stimulation. MRI was performed in stereotactic conditions before surgery. Brain parenchyma, caudate nucleus, putamen, pallidum, and red nucleus volumes and the surface of the mesencephalon were measured and normalized as percentages of the intracranial volume. Clinical evaluation was performed 1 month before and 6 months after surgery. RESULTS: The normalized brain parenchyma volume was lower in patients who were older and had a longer disease duration or a lower frontal score and was not predictive of the postoperative outcome. The residual scores for activities of daily living and parkinsonian motor disability were higher in patients with a smaller normalized mesencephalon. The normalized caudate nucleus volume was predictive of the pre- and postoperative levodopa-equivalent dosage. CONCLUSIONS: Brain atrophy is not an exclusion criterion for neurosurgery, indicating that patients' neurologic, psychiatric, and neuropsychological characteristics are the best predictive factors for neurosurgery. The fact that a smaller normalized mesencephalon surface was associated with a lower beneficial effect of the subthalamic nucleus stimulation on the parkinsonian motor disability suggests that the normalized mesencephalon surface is a predictive factor of the postoperative outcome.

Activities of Daily Living↗
PubMed2005

Does bilateral stimulation of the subthalamic nucleus aggravate apathy in Parkinson's disease?

OBJECTIVE: High frequency stimulation of the subthalamic nucleus (STN) dramatically decreases motor disability in patients with Parkinson"s disease (PD), but has been reported to aggravate apathy. The aim of this study was to analyse the effect of STN stimulation on motivation and reward sensitivity in a consecutive series of PD patients. METHODS: Apathy and reward sensitivity (Apathy Scale, Stimulus-Reward Learning, Reversal, Extinction, and Gambling tasks) were assessed in 18 PD patients treated by bilateral STN stimulation ("on" and "off" conditions) compared with 23 matched patients undergoing long term treatment with levodopa ("on" and "off" conditions). RESULTS: Apathy decreased under both STN stimulation and levodopa treatment, whereas explicit and implicit stimulus reward learning was unchanged. CONCLUSIONS: Bilateral STN stimulation in PD patients does not necessarily have a negative effect on motivation and reward sensitivity and can even improve apathy provided patients have been appropriately selected for neurosurgery.

Antiparkinson Agents↗
PubMed2005

Tourette's syndrome and deep brain stimulation.

In this prospective double blind randomised "N of 1" study, a patient with a severe form of Tourette's syndrome was treated with bilateral high frequency stimulation of the centromedian-parafascicular complex (Ce-Pf) of the thalamus, the internal part of the globus pallidus (GPi), or both. Stimulation of either target improved tic severity by 70%, markedly ameliorated coprolalia, and eliminated self injuries. Severe forms of Tourette's syndrome may benefit from stimulation of neuronal circuits within the basal ganglia, thus confirming the role of the dysfunction of limbic striato-pallido-thalamo-cortical systems in this disorder.

Adult↗
PubMed2005

Stimulation of the subthalamic nucleus in Parkinson's disease: a 5 year follow up.

BACKGROUND: The short term benefits of bilateral stimulation of the subthalamic nucleus (STN) in patients with advanced levodopa responsive Parkinson's disease (PD) are well documented, but long term benefits are still uncertain. OBJECTIVES: This study provides a 5 year follow up of PD patients treated with stimulation of the STN. METHODS: Thirty seven consecutive patients with PD treated with bilateral STN stimulation were assessed prospectively 6, 24, and 60 months after neurosurgery. Parkinsonian motor disability was evaluated with and without levodopa treatment, with and without bilateral STN stimulation. Neuropsychological and mood assessments included the Mattis Dementia Rating Scale, the frontal score, and the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: No severe peri- or immediate postoperative side effects were observed. Six patients died and one was lost to follow up. Five years after neurosurgery: (i) activity of daily living (Unified Parkinson Disease Rating Scale (UPDRS) II) was improved by stimulation of the STN by 40% ("off" drug) and 60% ("on" drug); (ii) parkinsonian motor disability (UPDRS III) was improved by 54% ("off" drug) and 73% ("on" drug); (iii) the severity of levodopa related motor complications was decreased by 67% and the levodopa daily doses were reduced by 58%. The MADRS was unchanged, but cognitive performance declined significantly. Persisting adverse effects included eyelid opening apraxia, weight gain, addiction to levodopa treatment, hypomania and disinhibition, depression, dysarthria, dyskinesias, and apathy. CONCLUSIONS: Despite moderate motor and cognitive decline, probably due to disease progression, the marked improvement in motor function observed postoperatively was sustained 5 years after neurosurgery.

Activities of Daily Living↗
PubMed2004

[Athetosis or dystonia?].

The term athetosis has progressively disappeared from the anglo-saxon literature which considers that athetosis is part of the spectrum of dystonia. These two clinical entities can be distinguished, however. Athetosis can be identified, searching for subtle semiological traits, in particular at the level of the hand. The earlier appearance of athetosis may be result from its onset during the early phases of development of the central nervous system. Despite its rarity, the clinical diagnosis of athetosis is important to consider from a prognostic point of view. Indeed, it results from brain lesions, and is therefore not a hereditary disorder as it may be the case for dystonia, and its evolution is relatively stable. The efficacy of treatments used in patients with dystonia, in particular high frequency pallidal stimulation, remains to be assessed in patients with athetosis. The concept of athetosis is still helpful in clinical practice.

Athetosis↗
PubMed2003

Screening for DJ-1 mutations in early onset autosomal recessive parkinsonism.

The DJ-1 gene was identified as responsible for early onset autosomal recessive parkinsonism in two families (PARK7). In this study, after excluding mutations in the parkin gene, the authors screened a large series of early onset autosomal recessive parkinsonism families and consanguineous isolated patients of diverse geographic origins for DJ-1 mutations. No mutations were found. This indicates that PARK7 is not a common locus for early onset autosomal recessive parkinsonism, and that one or more new loci remains to be identified.

Adolescent↗
PubMed2003

New parkin mutations and atypical phenotypes in families with autosomal recessive parkinsonism.

The frequency of parkin mutations was evaluated in 30 families of highly diverse geographic origin with early-onset autosomal recessive parkinsonism. Twelve different mutations, six of which were new, were found in 10 families from Europe and Brazil. Patients with parkin mutations had significantly longer disease duration than patients without the mutation but with similar severity of disease, suggesting a slower disease course. Two patients with parkin mutations had atypical clinical presentation at onset, with predominant tremor when standing.

Adult↗