Parkinson Disease: Houeto JL

Agid Y, Schüpbach M, Gargiulo M, Mallet L, Houeto JL, Behar C, Maltête D, Mesnage V, Welter ML. · Fédération des Maladies du Système Nerveux, Centre d'Investigation Clinique, INSERM U 679, Institut de Neurosciences, Université Paris VI, CHU Pitié-Salpêtrière, Paris, France. · J Neural Transm Suppl. · Pubmed #17017560 No free full text.

Abstract: 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.

Voon V, Kubu C, Krack P, Houeto JL, Tröster AI. · Department of Psychiatry, Toronto Western Hospital, Toronto, Canada. · Mov Disord. · Pubmed #16810676 No free full text.

Abstract: Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor, cognitive, neuropsychiatric, autonomic, and other nonmotor symptoms. The efficacy of deep brain stimulation (DBS) for the motor symptoms of advanced PD is well established. However, the effects of DBS on the cognitive and neuropsychiatric symptoms are less clear. The neuropsychiatric aspects of DBS for PD have recently been of considerable clinical and pathophysiological interest. As a companion to the preoperative and postoperative sections of the DBS consensus articles, this article reviews the published literature on the cognitive and neuropsychiatric aspects of DBS for PD. The majority of the observed neuropsychiatric symptoms are transient, treatable, and potentially preventable. Outcome studies, methodological issues, pathophysiology, and preoperative and postoperative management of the cognitive and neuropsychiatric aspects and complications of DBS for PD are discussed.

Houeto JL, Arnulf I. · Fédération de Neurologie, Centre d'Investigation Clinique, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. · Rev Neurol (Paris). · Pubmed #12690669 No free full text.

Abstract: Hallucinations (mainly visual), psychosis and excessive daytime sleepiness are potential side-effects of dopaminergic treatment. They may require a reduction or suppression of dopaminergic agonists, and the prescription of atypical neuroleptic agents or vigilance-enhancing drugs. The recent description of narcolepsy-like sleep onset in rapid eye movement sleep periods synchronous with hypnagogic hallucinations in patients with dopaminergic-induced psychosis or excessive daytime sleepiness, suggests that the mesodiencephalic lesions may predispose to the psychic effects of dopaminergic treatment. Disease-related mood disorders, sexual compulsions, gambling or levodopa addiction may also be amplified by the antiparkinsonian treatment. These complications illustrate the neuro-psychic aspect of Parkinson's disease: psychic troubles may result from a subtle balance between the direct effects of drugs, the pre-morbid pathological personality and the cortical and subcortical lesions.

Agid Y, Arnulf I, Bejjani P, Bloch F, Bonnet AM, Damier P, Dubois B, François C, Houeto JL, Iacono D, Karachi C, Mesnage V, Messouak O, Vidailhet M, Welter ML, Yelnik J. · Centre d'Investigation Clinique, INSERM U289, Hôpital de la Salpêtrière, France. · Adv Neurol. · Pubmed #12442695 No free full text.

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Damier P, Houeto JL, Bejjani BP, Arnulf I, Bonnet AM, Miloudy M, Agid Y. · Department of Neurology, Faculty of Medicine, University Hospital of Nantes, Nantes F-44035, France. · Adv Neurol. · Pubmed #11347233 No free full text.

This publication has no abstract.

Bonnet AM, Houeto JL. · Hôpital de la Pitié-Salpêtrière, Paris, France. · Biomed Pharmacother. · Pubmed #10349507 No free full text.

Abstract: Parkinson's disease is a progressive disease with selective dopaminergic neuronal loss. The pathophysiology is at present better understood with plurifactorial etiology, including genetic predisposition and environmental toxic factors. The mechanisms of cell death are based upon oxidative stress and apoptosis. The heterogeneity of dopaminergic neuronal loss leads to etiopathogenic clues. In the same way, the model of functional organization of basal ganglia circuitry gives a basis for further experimental and therapeutic research.

Payoux P, Remy P, Miloudi M, Houeto JL, Stadler C, Bejjani BP, Yelnik J, Samson Y, Rascol O, Agid Y, Damier P. · INSERM, U 825, CHU Toulouse, Toulouse, France. · J Cereb Blood Flow Metab. · Pubmed #18781162 No free full text.

Abstract: Continuous stimulation of the globus pallidus (GP) has been shown to be an effective treatment for Parkinson's disease (PD). We used the fact that the implanted quadripolar leads contain electrodes within the GPi and GPe to investigate the clinical effects of acute high-frequency stimulation applied in these nuclei and changes in regional cerebral blood flow (rCBF) as an index of synaptic activity. In five patients treated by chronic GP stimulation, we compared the effects on PD symptoms and the changes in rCBF at rest and during paced right-hand movements, with and without left GPe or GPi stimulation. Although improving contralateral rigidity and akinesia, left GPe stimulation decreased rCBF in the left cerebellum and lateral premotor cortex at rest and significantly increased it in the left primary sensorimotor cortex (SM1) during movement. In contrast, left ventral GPi stimulation, which improved rigidity and worsened akinesia, decreased rCBF in the left SM1, premotor area, anterior cingulum, and supplementary motor area but did not modify the movement-related activation. GPe stimulation seems to result in a reduced activity of motor-related areas and the facilitation of motor cortex activation during movement, the latter component being absent during GPi stimulation, and this may explain the observed worsening of akinesia.

Maltête D, Jodoin N, Karachi C, Houeto JL, Navarro S, Cornu P, Agid Y, Welter ML. · Centre d'Investigation Clinique, Fédération des Maladies du Système Nerveux, Institut National de la Santé et de la Recherche Médicale U-679, Université Pierre et Marie Curie, Paris, France. · J Neurophysiol. · Pubmed #17460099 links to  free full text

Abstract: High-frequency stimulation of the subthalamic nucleus (STN) is an effective treatment for severe forms of Parkinson's disease (PD). To study the effects of high-frequency STN stimulation on one of the main output pathways of the basal ganglia, single-unit recordings of the neuronal activity of the substantia nigra pars reticulata (SNr) were performed before, during, and after the application of STN electrical stimulation in eight PD patients. During STN stimulation at 14 Hz, no change in either the mean firing rate or the discharge pattern of SNr neurons was observed. STN stimulation at 140 Hz decreased the mean firing rate by 64% and the mean duration of bursting mode activity of SNr neurons by 70%. The SNr residual neuronal activity during 140-Hz STN stimulation was driven by the STN stimulation. How the decrease in rate and modification of firing pattern of SNr-evoked neural activity, during high-frequency STN stimulation, contribute to the improvement of parkinsonian motor disability remains to be elucidated.

Schüpbach M, Gargiulo M, Welter ML, Mallet L, Béhar C, Houeto JL, Maltête D, Mesnage V, Agid Y. · Centre d'Investigation Clinique, Fédération des Maladies du Système Nerveux, INSERM U679, Université Paris VI, CHU Pitié-Salpêtrière, Paris, France. · Neurology. · Pubmed #16801642 No free full text.

Abstract: 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.

Rodriguez-Oroz MC, Obeso JA, Lang AE, Houeto JL, Pollak P, Rehncrona S, Kulisevsky J, Albanese A, Volkmann J, Hariz MI, Quinn NP, Speelman JD, Guridi J, Zamarbide I, Gironell A, Molet J, Pascual-Sedano B, Pidoux B, Bonnet AM, Agid Y, Xie J, Benabid AL, Lozano AM, Saint-Cyr J, Romito L, Contarino MF, Scerrati M, Fraix V, Van Blercom N. · Department of Neurology and Neurosurgery, Clinica Universitaria and Medical School, University of Navarra and CIMA, Pamplona, Spain. · Brain. · Pubmed #15975946 links to  free full text

Abstract: 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.

Bonneville F, Welter ML, Elie C, du Montcel ST, Hasboun D, Menuel C, Houeto JL, Bonnet AM, Mesnage V, Pidoux B, Navarro S, Cornu P, Agid Y, Dormont D. · Service de Neuroradiologie, Centre d'Investigation Clinique, Hôpital de la Salpêtrière, Assistance-Publique-Hôpitaux de Paris, France. · Neurology. · Pubmed #15883323 No free full text.

Abstract: 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.

Mesnage V, Houeto JL, Bonnet AM, Clavier I, Arnulf I, Cattelin F, Le Fur G, Damier P, Welter ML, Agid Y. · Centre d'Investigation Clinique, Fédération de Neurologie and Inserm, Paris, France. · Clin Neuropharmacol. · Pubmed #15190231 No free full text.

Abstract: The neuropeptides neurokinin B, neurotensin, and anandamide, the endogenous ligands of NK3, NT1, and CB1 receptors respectively, are known to interact with brain dopaminergic transmission. This study evaluated the effects of these three antagonists of the NK3 (SR 142801), neurotensin (SR 48692), and cannabinoid (SR 141716) receptors on the severity of motor symptoms and levodopa-induced dyskinesias after administration of a single dose of levodopa in 24 patients with Parkinson disease. In this exploratory randomized, double-blind, placebo-controlled study, at the dose used, the drugs tested were well tolerated and could not improve parkinsonian motor disability.

Bonnet AM, Houeto JL. · Fédération de Neurologie, INSERM U289, Hôpital Pitié-Salpêtrière, 47 Bd de L'Hôpital, 75651 Paris. · Rev Neurol (Paris). · Pubmed #12486908 No free full text.

Abstract: The efficiency of pergolide has been confirmed by the study of a group 29 parkinsonian patients. They were relatively young, and the duration of evolution of their Parkinson's disease was more then ten years, with levodopa-induced dyskinesia and fluctuations. In this group of patients with most serious motor disability, it has been possible to improve dyskinesia and fluctuations with a relatively important dosage of pergolide and without increase of levodopa dosage.

Houeto JL, Mesnage V, Mallet L, Pillon B, Gargiulo M, du Moncel ST, Bonnet AM, Pidoux B, Dormont D, Cornu P, Agid Y. · Centre d'Investigation Clinique, Fédération de Neurologie and INSERM U 289, France. · J Neurol Neurosurg Psychiatry. · Pubmed #12023409 links to  free full text

Abstract: OBJECTIVE: to analyse 24 parkinsonian patients successfully treated by bilateral STN stimulation for the presence of behavioural disorders. METHOD: patients were evaluated retrospectively for adjustment disorders (social adjustment scale, SAS), psychiatric disorders (comparison of the results of psychiatric interview and the mini international neuropsychiatric inventory) and personality changes (IOWA scale of personality changes). RESULTS: parkinsonian motor disability was improved by 69.5% and the levodopa equivalent daily dosage was reduced by 60.5%. Social adjustment (SAS) was considered good or excellent in nine patients, moderately (n=14), or severely (n=1) impaired in 15 patients. Psychiatric disorders consisted of amplification or decompensation of previously existing disorders that had sometimes passed unnoticed, such as depressive episodes (n=4), generalised anxiety (n=18), and behavioural disorders with drug dependence (n=2). Appearance of mild to moderate emotional hyperreactivity was reported in 15 patients. Personality traits (IOWA scale) were improved in eight patients, unchanged in seven, and aggravated in eight CONCLUSION: Improvement in parkinsonian motor disability induced by STN stimulation is not necessarily accompanied by improvement in psychic function and quality of life. Attention is drawn to the possible appearance of personality disorders and decompensation of previous psychiatric disorders in parkinsonian patients who are suitable candidates for neurosurgery. We suggest that a careful psychological and psychiatric interview be performed before surgery, and emphasise the need for psychological follow up to ensure the best possible outcome.

Pillon B, Ardouin C, Damier P, Krack P, Houeto JL, Klinger H, Bonnet AM, Pollak P, Benabid AL, Agid Y. · INSERM EPI 007 and U 289, Fédération de Neurologie and Centre d'Investigation Clinique, Hôpital de la Salpêtrière, Paris, France. · Neurology. · Pubmed #10932277 No free full text.

Abstract: BACKGROUND: In a previous study on a consecutive series of 62 patients with PD, the authors showed that bilateral subthalamic or pallidal continuous high-frequency deep brain stimulation (DBS) affects neither memory nor executive functions 3 to 6 months after surgery. OBJECTIVE: To investigate the specific effects of DBS by comparing the performance of patients with the stimulator turned "on" and "off." METHODS: The performance of 56 patients on clinical tests of executive function was compared after 3 and 12 months of DBS of the subthalamic nucleus (STN; n = 48) or the internal globus pallidus (GPi; n = 8) with the stimulator "on" or "off." Global intellectual efficiency, verbal learning, and mood were also evaluated with the stimulator "on." The performance of another group of 20 patients was compared after 6 months of DBS of the STN (n = 15) or the GPi (n = 5) with the stimulator "on" or "off" on more experimental tests recently shown to be more sensitive to l-dopa therapy. RESULTS: When the stimulator was "on," STN patients showed a mild but significant improvement in psychomotor speed and working memory. In comparison with the presurgical state, STN patients had no cognitive deficit at 12 months, except for lexical fluency. There was no differential effect of STN or GPi stimulation. CONCLUSIONS: 1) The specific effect of DBS seems to mimic the action of l-dopa treatment in the cognitive as in the motor domain; 2) the surgery associated with DBS does not appear to affect the cognitive performance of patients with PD 12 months later, except for a mild deficit in lexical fluency.

Houeto JL, Damier P, Bejjani PB, Staedler C, Bonnet AM, Arnulf I, Pidoux B, Dormont D, Cornu P, Agid Y. · Centre d'Investigation Clinique, Fédération de Neurologie and Institut National de la Santé et de la Recherche Médicale, Unit 289, Paris, France. · Arch Neurol. · Pubmed #10768618 links to  free full text

Abstract: BACKGROUND: High-frequency stimulation of the subthalamic nucleus constitutes a therapeutic advance for severely disabled patients with Parkinson disease. OBJECTIVE: To evaluate the efficacy and safety of continuous bilateral high-frequency stimulation of the subthalamic nucleus in patients with Parkinson disease. DESIGN: A prospective study of patients with Parkinson disease treated at a university hospital. PATIENTS AND METHODS: Electrodes were implanted bilaterally in the subthalamic nucleus of 23 consecutive patients with Parkinson disease who responded well to levodopa but had severe motor complications. There were 16 men and 7 women (mean +/- SEM age, 53 +/- 2 years) who had a mean +/- SEM disease duration of 14.7 +/- 1.0 years. Targets were determined by 3-dimensional magnetic resonance imaging, combined with intraoperative electrophysiologic recordings and stimulation. RESULTS: Six months after surgery, motor disability, levodopa-induced motor fluctuations, dyskinesias, and the daily dose of levodopa equivalent decreased significantly by 67%, 78%, 77%, and 61%, respectively, compared with the preoperative state. No significant morbidity was observed, except transient depression in 4 patients. CONCLUSIONS: The beneficial effects of subthalamic stimulation depend on (1) the criteria used for patient selection, (2) the precision with which the subthalamic nucleus is targeted (dependent on the 3-dimensional magnetic resonance imaging and the intraoperative electrophysiologic and clinical assessments), and (3) the long-term postoperative adjustment of stimulation variables.

Moro E, Allert N, Eleopra R, Houeto JL, Phan TM, Stoevelaar H, Anonymous00028. · Movement Disorders Center, University of Toronto, UHN, Toronto Western Hospital, 399 Bathurst Street, 7MCL 7-402, Toronto ON M5T 2S8, Canada. · J Neurol. · Pubmed #19221846 No free full text.

Abstract: BACKGROUND AND OBJECTIVE: Although Deep Brain Stimulation (DBS) has been proven to be an effective treatment for patients with advanced Parkinson's disease (PD), it may be difficult for general neurologists to identify appropriate candidates for this procedure. We developed an electronic decision tool that can assist neurologists in deciding which PD patients should be referred for DBS consideration. METHODS: Using the RAND/UCLA Appropriateness Method, an international expert panel assessed the appropriateness of referral for 972 theoretical patient profiles. Panel results were embedded in an electronic decision support tool which displays the panel statement on referral (appropriate, inappropriate and uncertain) after completion of the patient profile. RESULTS: Referral was considered appropriate for 33% of the theoretical profiles. Logistic regression showed excellent internal consistency of the ratings (predictive value 92%). Symptom severity (OFF-symptoms, dyskinesias, refractory tremor) and PD duration were positively associated with the panel judgment that referral is appropriate. Presence of levodopa-resistant axial symptoms, age >or= 70 years and presence of cognitive impairment showed the strongest negative impact. CONCLUSIONS: The RAND/UCLA method proved to be useful in determining the appropriate criteria for DBS referral. Validity and applicability of the decision tool (accessible via http://test.stimulus-dbs.org) in clinical practice need to be further determined.

Beato R, Levy R, Pillon B, Vidal C, du Montcel ST, Deweer B, Bonnet AM, Houeto JL, Dubois B, Cardoso F. · INSERM U610, Groupe Hospitalier de la Pitié-Salpêtrière, Paris, France. · Arq Neuropsiquiatr. · Pubmed #18545772 links to  free full text

Abstract: OBJECTIVE: To evaluate the clinical features of the working memory (WM) in Parkinson's disease (PD) patients and to test the effect of levodopa on WM. METHOD: The paradigm was based on the 'n-back' tasks, which enables to study the level of executive demand (three levels of difficulty) and the domain of the information being processed (spatial items, faces and letters). The effect of levodopa was studied by testing PD patients in "on" and "off" states. RESULTS: PD patients performed less well in WM tasks than controls. There was no interaction between groups and complexity. Levodopa therapy had a positive effect only on spatial WM tasks but no effect on complexity. CONCLUSION: Our results suggest that impairment observed may result from a maintenance deficit within WM regardless the level of processing and levodopa therapy presents a positive effect on spatial WM.

Bonneville F, Bloch F, Kurys E, du Montcel ST, Welter ML, Bonnet AM, Agid Y, Dormont D, Houeto JL. · Service de Neuroradiologie, Hôpital de la Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, 47 Boulevard de l'Hôpital, 75651, Paris Cedex 13, France. · Eur Radiol. · Pubmed #18351343 No free full text.

Abstract: Camptocormia is characterized by an excessive anterior flexion of the spine that appears only when standing or walking. The origin of this symptom remains unknown, but recent clinical reports of camptocormia associated with Parkinson's disease (PD) suggest cerebral involvement in the pathogenesis of camptocormia. This study was undertaken to investigate the hypothesis that camptocormia in PD has a central origin. Seventeen PD patients with camptocormia were prospectively enrolled and were compared to 10 matched PD patients without camptocormia and 12 normal controls. The normalized volumes of the brain, striatal nuclei, and the cross-sectional areas of the midbrain and pons were measured on three-dimensional magnetic resonance imaging. Data were correlated with the severity of the symptoms. The normalized axial surface of the midbrain was statistically smaller in PD patients with camptocormia than in normal controls (P = 0.01). The normalized volumetric data were not statistically different in PD patients with camptocormia. There was a significant negative correlation between the severity of camptocormia and the normalized brain volume (P < 0.009; R = -0.649) and sagittal pons area (P < 0.01; R = -0.642). The results suggest that PD with camptocormia may represent a selective form of PD in which a specific neuronal dysfunction possibly occurs within the brainstem.

Schüpbach WM, Maltête D, Houeto JL, du Montcel ST, Mallet L, Welter ML, Gargiulo M, Béhar C, Bonnet AM, Czernecki V, Pidoux B, Navarro S, Dormont D, Cornu P, Agid Y. · Centre d'Investigation Clinique, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. · Neurology. · Pubmed #17151341 No free full text.

Abstract: 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.

Schüpbach MW, Welter ML, Bonnet AM, Elbaz A, Grossardt BR, Mesnage V, Houeto JL, Maltête D, Mallet L, Rocca WA, Mallet A, Agid Y. · Centre d'Investigation Clinique, Fédération de Neurologie and National Institute of Health and Medical Research (INSERM) Unit 679 (former Unit 289), Hôpital de la Salpêtrière, Paris, France. · Mov Disord. · Pubmed #17149702 No free full text.

Abstract: Subthalamic nucleus (STN) stimulation improves motor disability and quality of life in patients with advanced Parkinson's disease (PD). Short-term mortality is low, but little is known about long-term mortality. We assessed mortality and causes of death in 171 consecutive PD patients treated by STN stimulation. Surgery was performed after a median lagtime of 13 years from PD onset at a median age of 57 years. The median follow-up after surgery was 41 months. Sixteen patients died 8 to 83 months after neurosurgery. Poorer cognitive function was the only predictive factor for mortality (standardized mortality ratio = 2.9; 95% confidence interval [CI], 1.6-4.7; P < 0.0001). Based on a historical comparison of 118 operated patients with 39 nonoperated patients from a different population, survival among operated patients was not better (hazard ratio = 1.2; 95% CI, 0.7-2.1).

Houeto JL, Mallet L, Mesnage V, Tezenas du Montcel S, Béhar C, Gargiulo M, Torny F, Pelissolo A, Welter ML, Agid Y. · Centre d'Investigations Cliniques, Hôpital de la Salpêtrière, 47 Boulevard de l'Hôpital, 75013 Paris, France. · Arch Neurol. · Pubmed #16908734 links to  free full text

Abstract: BACKGROUND: Bilateral subthalamic high-frequency stimulation significantly improves motor functions in patients with advanced forms of Parkinson disease (PD). This favorable effect contrasts with a growing number of reports that the treatment may result in psychiatric complications. OBJECTIVE: To analyze the presence of behavioral disorders and social maladjustment in PD patients successfully treated with continuous bilateral subthalamic stimulation. DESIGN: Prospective study. SETTING: University hospital. METHODS: Twenty PD patients underwent prospective evaluation for behavioral and personality changes, quality of life, and social functioning, 6 and 24 months after surgery to implant bilateral stimulating electrodes within the subthalamic nucleus. RESULTS: At 6 and 24 months after surgery, parkinsonian motor disability (on-stimulation/off-medication) was improved by 81% and 67%, respectively, and the severity of levodopa-related motor complications was improved by 84% and 70%, respectively. Levodopa-equivalent dosage was decreased by 79% and 66%, respectively; severity of depression was improved by 21% and 33%, respectively; and severity of anxiety was improved by 43% and 64%, respectively. The patients' personality traits were unmodified. Twenty-four months after surgery, the global score for quality of life was improved by 28%, whereas scores for social adjustment remained stable. CONCLUSIONS: Provided that patients with PD are rigorously selected for neurosurgery, subthalamic stimulation (1) improves mood, anxiety, and quality of life; (2) does not result in severe permanent psychiatric disorders or modify patients' personality; and (3) does not ameliorate social adaptation.

Lang AE, Houeto JL, Krack P, Kubu C, Lyons KE, Moro E, Ondo W, Pahwa R, Poewe W, Tröster AI, Uitti R, Voon V. · Department of Neurology, Toronto Western Hospital, Toronto, Ontario, Canada. · Mov Disord. · Pubmed #16810718 No free full text.

Abstract: Numerous factors need to be taken into account in deciding whether a patient with Parkinson's disease (PD) is a candidate for deep brain stimulation. Patient-related personal factors including age and the presence of other comorbid disorders need to be considered. Neuropsychological and neuropsychiatric concerns relate both to the presurgical status of the patient and to the potential for surgery to result in new problems postoperatively. A number of factors related to the underlying PD need to be considered, including the specific parkinsonian motor indications (e.g., tremor, bradykinesia, gait dysfunction), previous medical therapies, including benefit from current therapy and adverse effects, and past surgical treatments. Definable causes of Parkinsonism, particularly atypical Parkinsonisms, should be considered. Finally, methods of evaluating outcomes should be defined and formalized. This is a report from the Consensus on Deep Brain Stimulation for Parkinson's Disease, a project commissioned by the Congress of Neurological Surgeons and the Movement Disorder Society (MDS). The report has been endorsed by the Scientific Issues Committee of the MDS and the American Society of Stereotactic and Functional Neurosurgery. It outlines answers to a series of questions developed to address all aspects of deep brain stimulation preoperative decision-making.

Bloch F, Houeto JL, Tezenas du Montcel S, Bonneville F, Etchepare F, Welter ML, Rivaud-Pechoux S, Hahn-Barma V, Maisonobe T, Behar C, Lazennec JY, Kurys E, Arnulf I, Bonnet AM, Agid Y. · Centre d'Investigation Clinique-Fédération des Maladies du Système Nerveux, Groupe-Hospitalier Pitié-Salpêtrière, Paris, France. · J Neurol Neurosurg Psychiatry. · Pubmed #16754693 No free full text.

Abstract: 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.

Fraix V, Houeto JL, Lagrange C, Le Pen C, Krystkowiak P, Guehl D, Ardouin C, Welter ML, Maurel F, Defebvre L, Rougier A, Benabid AL, Mesnage V, Ligier M, Blond S, Burbaud P, Bioulac B, Destée A, Cornu P, Pollak P, Anonymous00009. · Department of Neurology and Neurosurgery, Grenoble University Hospital and INSERM U318 Joseph Fourier University, Grenoble Cedex 9, France. · J Neurol Neurosurg Psychiatry. · Pubmed #16543519 links to  free full text

Abstract: BACKGROUND: High frequency stimulation of the subthalamic nucleus (STN) is an alternative but expensive neurosurgical treatment for parkinsonian patients with levodopa induced motor complications. OBJECTIVE: To assess the safety, clinical effects, quality of life, and economic cost of STN stimulation. METHODS: We conducted a prospective multicentre study in 95 consecutive Parkinson's disease (PD) patients receiving bilateral STN stimulation and assessed its effects over 12 months. A double blind randomised motor evaluation was carried out at 3 month follow up, and quality of life, self care ability, and predictive factors of outcome following surgery were assessed. The cost of PD was estimated over 6 months before and after surgery. RESULTS: The Unified Parkinson's Disease Rating Scale (UPDRS) motor score improved by 57% (p<0.0001) and activities of daily living improved by 48% (p<0.0001) at 12 month follow up. Double blind motor scoring improved by 51% at 3 month follow up (p<0.0001). The total PD Quality of Life Questionnaire (PDQL-37) score improved by 28% (p<0.001). The better the preoperative motor score after a levodopa challenge, the better the outcome after STN stimulation. Five patients developed an intracerebral haematoma during electrode implantation with permanent after effects in two. The 6 month costs of PD decreased from 10,087 euros before surgery to 1673 euros after surgery (p<0.0001) mainly because of the decrease in medication. These savings allowed a return on the procedure investment, estimated at 36,904 euros over 2.2 years. CONCLUSIONS: STN stimulation has good outcomes with relatively low risk and little cost burden in PD patients with levodopa induced motor complications.