L-DOPA-induced dyskinesias, motor fluctuations and health-related quality of life: the COPARK survey.

BACKGROUND AND PURPOSE: Studies assessing the correlations between L-DOPA-induced dyskinesias (LIDs) and motor fluctuations with health-related quality of life (HRQoL) in Parkinson's disease (PD) have yielded conflicting results. This study aimed to assess the relationship between LIDs and motor fluctuations with HRQoL in patients with PD, and to assess the relative contribution of their severity and duration in a large sample of patients with PD. METHODS: A total of 683 patients with PD from the COPARK survey were evaluated. HRQoL was assessed using the 39-Item Parkinson's Disease Questionnaire (PDQ-39) (primary outcome) and 36-Item Short Form Survey (SF-36). The daily duration and severity of LIDs were obtained from Unified Parkinson's Disease Rating Scale (UPDRS) IV items 32 and 33, respectively. The daily duration of motor fluctuations was obtained from UPDRS IV item 36 and severity was estimated as the difference between the UPDRS 2 (Activities of Daily Living) score in 'OFF' versus 'ON' condition. RESULTS: A total of 235 patients with PD (35%) experienced motor fluctuations and 182 (27%) experienced LIDs. The PDQ-39 total and SF-36 physical scores were significantly worse in patients with LIDs, after adjusting for the presence of motor fluctuations. The PDQ-39 total score and SF-36 physical and mental score were significantly worse in patients with motor fluctuations, after adjusting for the presence of LIDs. The severity of LIDs and the duration of motor fluctuations significantly and independently affected PDQ-39 scores. The SF-36 physical score was affected only by the severity of motor fluctuations, whereas the mental score was not affected by any of the aforementioned variables. CONCLUSION: Our findings suggest that LIDs (mainly their severity) and motor fluctuations (mainly their duration) correlate independently with HRQoL in patients with PD.

[Continuous subcutaneous infusion of apomorphine in Parkinson's disease: retrospective analysis of a series of 81 patients]. / Le traitement par apomorphine en perfusion continue sous-cutanée dans la maladie de Parkinson : analyse rétrospective d'une série de 81 patients.

BACKGROUND: Continuous subcutaneous infusion of apomorphine (CAI) has shown efficacy in the treatment of motor fluctuations but its place in the therapeutic arsenal remains poorly defined in terms of indication, acceptability and long-term tolerance. Indeed, few studies have been carried out with a follow-up greater than 12 months. The main objective was to assess the quality of life of Parkinson's disease (PD) patients treated with CAI. We also evaluate the effectiveness on the motor fluctuations, the long-term tolerance of this treatment with its causes of discontinuation and the treatment regimens used. METHODS: We conducted a retrospective study of 81 PD patients treated with CAI between April 2003 and June 2012. Data were collected from medical records. A repeated measures analysis of variance by the linear mixed model was used (significance level: 5%). RESULTS: In August 2012, 27/81 patients were still treated with CAI with a mean duration of 28 months, 46/81 discontinued CAI (9 precociously), and 8 were lost to view. We didn't show improvement in the quality of life nor efficacy of CAI on the UPDRS IV score (P=0.54) and dyskinesia score (P=0.95). The CGI score patient also reflects this result with a majority response suggesting no significant change with CAI. We observed relative good cognitive and psychiatric tolerance. Adverse events were frequent but often benign. The average (±SD) rate of apomorphine was 3.15±1.71 mg/h and the oral dopaminergic treatment was decreased by 37.8%. DISCUSSION: The results are consistent with the literature except for the lack of efficiency on motor fluctuations which may be due to the use of too small doses of apomorphine. This seems to be a leading cause of discontinuation of CAI, especially when it is associated with side effects or important constraints. For better efficiency on motor fluctuations, we recommend the use of apomorphine at higher doses to obtain an optimal continuous dopaminergic stimulation.

Oro-buccal symptoms (dysphagia, dysarthria, and sialorrhea) in patients with Parkinson's disease: preliminary analysis from the French COPARK cohort.

INTRODUCTION: Abnormal oro-buccal functions including dysarthria, sialorrhea and dysphagia commonly affect patients with Parkinson's disease (PD). OBJECTIVES: To estimate the prevalence of such oro-buccal symptoms at baseline in the first 419 patients with PD included in the COPARK cohort and to analyze their correlations with patients' demographics, clinical characteristics, and drugs consumption. METHODS: Patients were assessed using the Unified PD Rating Scale, the Hospital Anxiety and Depression Scale, and the PDQ-39. Dysarthria, sialorrhea, and dysphagia were defined as UPDRS items 5, 6, or 7 ≥ 1. RESULTS: Dysarthria, sialorrhea, or dysphagia were present in 51%, 37%, or 18% out of the 419 patients, respectively. At least one of these symptom was present in 267/419 patients (65%), whilst a combination of symptoms was present in 136/419 (33%). Logistic regression showed that the presence of each of the three oro-buccal symptoms was significantly correlated with that of the two others. Other correlations included male gender, hallucinations, disease severity, levodopa use and lack of opiates consumption for dysarthria; disease severity, orthostatic hypotension and absence of antidepressants consumption for sialorrhea; female gender, motor fluctuations, and depressive symptoms for dysphagia. None of the three oro-buccal symptoms were associated with a reduced PDQ-39 score. CONCLUSION: Oro-buccal symptoms were present in two of three patients with moderate PD, the presence of each symptoms being significantly correlated with that of the two others.

[Impulse control disorders in Parkinson's disease: A cohort of 35 patients]. / Troubles du contrôle des impulsions associés à la maladie de Parkinson : étude d'une cohorte de 35 patients.

INTRODUCTION: Impulse control disorders (ICDs) in Parkinson's disease (PD) are associated with dopamine agonist treatment. Although discontinuation of dopamine agonist is recommended, ICD management has not been precisely stated. The aims of the study were to describe demographic and clinical characteristics in a group of PD patients with ICDs and to evaluate the management of dopamine agonist treatment proposed to the same patients in order to treat the ICDs. METHODS: Thirty-five PD patients with ICD and 607 PD patients without ICD were studied. In the ICD group, demographic and clinical data were collected prospectively (ICD characteristics, motor and cognitive evaluation); demographic and clinical data were obtained retrospectively in the group without ICD. RESULTS: In the ICD group, the sex ratio was 2.9 (versus 1.2 in the absence of ICD; p<0.05), the mean age was 57.5 years (versus 66.9 years; p<0.01) and the mean age at PD onset was 48.3 years (versus 55.5 years; p<0.01). All ICD patients were receiving a dopamine agonist when the ICD started (versus 50.9 % of patients receiving a dopamine agonist in the absence of ICD; p<10(-6)). In mean, ICDs started 2.8 years before they were diagnosed. No particular dopamine agonist was associated with ICDs more frequently than the others. Discontinuation of the dopamine agonist was the treatment the more frequently associated with the recovery of ICDs (93.3 %). Dose lowering and the change of dopamine agonist resulted in complete regression of ICDs respectively in 9.1% and 33.3% of patients. CONCLUSION: Young age, male gender and young age at PD onset are frequent in PD patients developing ICDs, as already described in American or Asian cohorts. We highlighted a long diagnosis delay and confirmed the strong efficacy of dopamine agonist withdrawal.

Molecular analyses of the LRRK2 gene in European and North African autosomal dominant Parkinson's disease.

BACKGROUND: Mutations in the leucine-rich-repeat kinase 2 (LRRK2) gene have been identified in families with autosomal dominant Parkinson's disease (ADPD), the most common of which is the p.G2019S substitution that has been found at varying frequencies worldwide. Because of the size of the LRRK2 gene, few studies have analysed the entire gene in large series of ADPD families. METHODS: We performed extensive mutation analyses of all 51 coding exons of the LRRK2 gene in index cases from 226 Parkinson's disease families compatible with autosomal dominant inheritance, mostly from France (n = 182) and North Africa (n = 14). RESULTS: We found 79 sequence variants, 29 of which were novel. Eight potentially or proven pathogenic mutations were found in 22 probands (9.7%). There were four novel amino acid substitutions that are potentially pathogenic (p.S52F, p.N363S, p.I810V, p.R1325Q) and two novel variants, p.H1216R and p.T1410M, that are probably not causative. The common p.G2019S mutation was identified in 13 probands (5.8%) including six from North Africa (43%). The known heterozygous p.R1441H and p.I1371V mutations were found in two probands each, and the p.E334K variant was identified in one single patient. Most potentially or proven pathogenic mutations were located in the functional domains of the Lrrk2 protein. CONCLUSION: This study leads us to conclude that LRRK2 mutations are a common cause of autosomal dominant Parkinson's disease in Europe and North Africa.

[Mechanisms of deregulated response to hypoxia in sporadic amyotrophic lateral sclerosis: a clinical study]. / Mécanismes de dérégulation de la réponse à l'hypoxie dans la sclérose latérale amyotrophique.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of upper and lower motorneurons, leading to death in 3 to 5 years. Respiratory insufficiency and hypoxemia are closely linked during the clinical course of ALS. Chronic respiratory insufficiency and hypoxemia generally occur late in the disease course but rapid episodes of intermittent hypoxemia followed by reoxygenation can occur early and insidiously. Two pathways are involved in the response to hypoxemia: (i) hypoxia inducible factor-1 (HIF-1) and VEGF/HIF-2 and an erythropoietin (EPO) mediated pathway, in response to prolonged hypoxemia; and (ii) nuclear factor kappa-B (NFkappa-B) during acute hypoxemia followed by reoxygenation episodes, inducing inflammatory mediators: interleukin-6 (IL-6), TNF-alpha, cyclo oxygenase-2 (COX-2) and prostaglandin E-2 (PGE-2). Our aim was to specify the role of the different functional pathways of response to hypoxemia in sporadic ALS patients, compared with neurological controls and according to the level of hypoxemia. We report the results of several studies of hypoxemic and/or inflammatory mediators in the cerebrospinal fluid (CSF) from ALS patients, according to their respiratory status, showing a selective defect of HIF-1 mediated angiogenic factors (VEGF and angiogenin [ANG]) during chronic hypoxia in sporadic ALS patients, compared to hypoxemic neurological controls; contrasting with an early activation of the NFkappa-B pathway since the isolated desaturation stage (IL-6, TNF-alpha, PGE-2, angiopoietin-2) in the same cohort of sporadic ALS patients. All these results are consistent with a selective impairment of the HIF-1 pathway during chronic hypoxemia in ALS patients. Inflammatory mediators were strongly elevated, since the early stage of the disease until chronic hypoxemia, suggesting a compensatory mechanism.

[Continuous dopaminergic stimulation by Duodopa in advanced Parkinson's disease: Efficacy and safety]. / Intérêts de la stimulation dopaminergique continue par Duodopa((R)) dans la maladie de Parkinson évoluée : efficacité et tolérance.

INTRODUCTION: When advanced Parkinson's disease (PD) patients experience motor complications (fluctuations and dyskinesias) despite standard oral treatment, two treatment options are available: deep brain stimulation and subcutaneous apomorphine infusion with respects of indications for each strategy. Continuous intraduodenal infusion of levodopa (Duodopa) via a gastrojejunal tube may be proposed at this stage of the disease and the study of indications and clinical results with Duodopa may develop this new therapeutic alternative. PATIENTS AND METHODS: Seven patients with advanced PD (dementia for all and psychiatric disorders for some of them, axial signs) were treated with Duodopa. We evaluated neuropsychological functions, all UPDRS scales, gait and quality-of-life just before Duodopa onset and six months after treatment end. Moreover, we described all adverse events (early and late) and studied daily levodopa doses before and 6 months after treatment. RESULTS: We demonstrated an improvement in motor UPDRS (44%), in axial signs (40% for UPDRS part III axial subscore and 12% for gait) and a reduction of fluctuations (37.5%) and in UPDRS part IV dyskinesia (20%). These significant results are observed without any change in the quality-of-life. Adverse events were due to PEG positioning for four patients, the equipment (pump, connection, inner tube) for all patients and levodopa for four patients. Daily levodopa dose had to be increased 13.5%. CONCLUSION: Duodopa can be considered as a new treatment strategy providing significant improvements in motor fluctuations, dyskinesia and severe axial signs. These results were demonstrated in very advanced PD patients, who had been excluded from previous studies, with cognitive disorders and for some of them dopaminergic psychosis well controlled by medications.

[Classification of parkinsonian syndromes via factorial discriminant analysis of brain SPECT data]. / Intérêt de l'analyse factorielle discriminante pour classer les syndromes parkinsoniens à partir de la tomoscintigraphie d'émission monophotonique.

INTRODUCTION: The objective was to assess the value of single photon emission computerized tomography (SPECT) and factorial discriminant analysis (FDA) in the differential diagnosis of Parkinson's disease (PD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). PATIENTS AND METHODS: Sixty-two patients with clinical diagnoses of either CBD, PSP or PD were studied using brain HmPaO-SPECT. Thirteen pairs of regions of interest (ROIs) were drawn on the slices located 50mm and 90mm above the canthomeatal plane. Twenty-six uptake indices and 13 asymmetry indices were determined. FDA was performed in order to determine whether or not the patients could be classified into the correct clinical group on the basis of SPECT data alone. The most discriminant parameters were used to generate two predictive scores, which were tested in a second group of 15 patients. RESULTS: FDA of all 39 variables correctly classified all the patients. A subset of 10 variables was used to build predictive scores, which correctly classified 90% of PD patients, 100% of PSP patients and 86% of CBD patients. When tested in the validation group of 15 patients, these predictive scores correctly classified 87% of the individuals. The frontal medial, temporoparietal and parietal regions were the most discriminant. CONCLUSION: Using SPECT data alone, this study enabled us to distinguish between PD, PSP and CBD in patients with clear clinical presentations of the diseases in question. This novel, statistical approach provides reliable information. However, a prospective study dealing with de novo parkinsonian syndromes will be necessary.

[Issues of France's "Leonetti Act": Involvement of amyotrophic lateral sclerosis patients in prior discussions concerning respiratory support and end-of-life care]. / Les enjeux de la loi Leonetti: participation des patients atteints de sclérose latérale amyotrophique à une discussion anticipée sur la réanimation respiratoire et les soins de fin de vie.

In accordance with the principle of personal autonomy, expert consensus statements on amyotrophic lateral sclerosis (ALS) recommend early engagement with terminal-phase patients on the type of symptomatic treatment to be administered in the event of respiratory failure, since decompensation progresses too rapidly to allow time for a discussion. The French Parliamentary Act on Patients' Rights and End-of-Life Care (dated 22 April 2005) grants individuals the right to refuse unreasonable treatment and obliges physicians to take account of any prior instructions given by a person before he/she became incapable of communicating. The provision of prior instructions is a very reassuring situation for the physician: the autonomous patient indicates his or her choice of end-of-life care. However, there are two pitfalls which must be avoided: (i) holding a discussion for the sole purpose of obtaining prior instructions and (ii) not acknowledging the patient's vulnerability. The present study dealt with 35 ALS patients for whom the question of either intensive care or palliative end-of-life care remained open. Even though the great majority of these individuals were keen to know their exact state of health, 48% refused to consider this circumstance and only 20% expressed prior instructions. These results prompted us to question the ethical dimension of the concept of autonomy beyond its founding formulation: can one envisage an incapacity to confront oneself with the existential question of possible death? In 80% of cases, the physician will have to take a care decision in the absence of any prior instructions from the patient. This amounts to more than respecting a person's autonomy and involves exercising medical responsibility.

Is the early-onset torsion dystonia (EOTD) linked to TOR1A gene as frequent as expected in France?

Early onset torsion dystonia are rare movement disorders. Molecular defect is known for only a subgroup, consisting of a unique and recurrent mutation in the TOR1A gene. We undertook a nationwide census of French TOR1A-mutation carriers and the assessment of clinical associated signs. Overall, 53 index cases and 104 relatives were studied and haplotypes linked to the mutation constructed. The previously reported Ashkenazi-Jewish haplotype was found in 11 families with the remainder carrying distinct haplotypes suggesting independent mutation events. This study demonstrates the scarcity of this disease in France with estimated disease frequency of 0.13:100,000 and mutation frequency of 0.17:100,000.

Anticipatory postural adjustments associated with arm movement in Parkinson's disease: a biomechanical analysis.

OBJECTIVE: To study anticipatory postural adjustments (APAs) in Parkinson's disease (PD) via a biomechanical analysis, including vertical torque (Tz). METHODS: Ten patients with PD (in the "off-drug" condition) and 10 age matched controls were included. While standing on a force platform, the subject performed a right shoulder flexion in order to grasp a handle in front of him/her, under three conditions (all at maximal velocity): movement triggered by a sound signal and loaded/non-loaded, self-paced movement. The anteroposterior coordinates of the centre of pressure (COP) and Tz were calculated. RESULTS: A group effect was observed for Tz and COP in patients with PD (compared with controls): the maximal velocity peak appeared later and the amplitude of the COP backward displacement and the area of the positive phase of Tz were lower, whereas the duration of the positive phase of Tz was greater. Interaction analysis showed that the area of Tz was especially affected in the triggered condition and the loaded, self-paced condition. The onset of the COP backward displacement was delayed in the triggered condition. CONCLUSION: Our biomechanical analysis revealed that patients with PD do indeed perform APAs prior to unilateral arm movement, although there were some abnormalities. The reduced APA magnitude appears to correspond to a strategy for not endangering postural balance.

Slowly progressive spinocerebellar ataxia with extrapyramidal signs and mild cognitive impairment (SCA21).

Spinocerebellar ataxia 21 is a slowly progressive and mild ataxia associated with extrapyramidal signs. Affected subjects exhibit a moderate gait and limb ataxia variably associated with akinesia, tremor, rigidity, hyporeflexia, and mild cognitive impairment. The responsible gene has been assigned to a 19 Mbases interval on chromosome 7p in a single French family. No evidence of significant linkage to this locus was found in 21 other families obtained from the EUROSCA consortium. The locus interval contains several candidate genes that could be responsible for the disease. Direct sequencing of NDUFA4, PHF14, KIAA0960, ARLA4, ETV1, DGKB, HDAC9, FERD3L, ITGB8, and SP4 genes were performed, but all the direct mutation analyses were negative excluding pathogenic mutations associated with the disease. Therefore, the gene responsible for SCA21 remains to be identified.

[Evolution of locomotion disorders in Huntington's disease]. / Caractéristiques évolutives des troubles de locomotion dans la maladie de Huntington.

INTRODUCTION: Locomotion disorders are important in Huntington's disease (HD). Although the rates of evolution of motor, functional or cognitive aspects of HD have been studied, the evolution of locomotion disorders in early stages of the disease remains unknown. OBJECTIVES: To determine the rate of evolution of the HD-associated gait and gait initiation disorders and their correlates. PATIENTS AND METHODS: Eighteen HD patients were recorded with a minimum interevaluation interval of one year. Akinesia was studied by evaluating the anticipatory postural adjustment (APA) phase preceding the first step. We also evaluated gait speed, stride time and stride length. RESULTS: We observed an alteration in the APA phase, whose evolution was correlated with that of akinesia. We also observed a decrease in gait speed, which was due both to an increase in stride time and a decrease in stride length. Stride-to-stride variability did not worsen between both evaluations. CONCLUSIONS: A worsening in both gait initiation and gait performance was observed in HD. Initial weak functional capacity and more severe motor impairment seem to be associated with a faster progression of locomotion parameters in these mildly impaired HD patients.

Seizure after use of almotriptan.

We report the case of a young woman who suffered from a seizure after use of almotriptan. There was a recurrence with ergotamine. We discuss possible link with susceptibility genes.

[About Huntington's disease: role of families and health professionals in information transmission]. / A propos de la maladie de Huntington : rôles respectifs de la famille et des professionnels de santé dans la transmission de l'information.

INTRODUCTION: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. However, little information is available concerning the way each patient learns about the existence of Huntington's disease in his family and the way he transmits the information to his descendants. This study aims to specify the role of families and healthcare professionals in delivering information about the disease and its hereditary risk. PATIENTS AND METHODS: Data from 105 consecutive patients were analyzed. The patients were categorized in four classes according to the way they received information about HD in their family: firstly, families where the disease was known; secondly, families where the HD was "poorly known"; thirdly, families where no antecedent could be found; fourthly, families where the disease was voluntarily hidden. The majority (52%) of the patients did not know the name of HD before being diagnosed. The patient choices for disclosure of hereditary risks to their relatives were influenced by the information they received about the disease in their own family. Patients from the second category (disease "poorly known") had the most difficulty in transmitting the information. DISCUSSION: Despite the high risk of transmission, information about the disease is poorly known and transmitted in families concerned by HD. Although healthcare professionals confronted with the question of information delivery to relatives must always respect patient confidentiality, our results underline the need to more fully inform patients about the disease and transmission patterns. More help from healthcare professionals is needed to accompany HD patients concerning the question of transmitting information. The efficacy of a specific educational program should be assessed.

[Superficial hemosiderosis of the central nervous system improved by corticosteroids]. / Hémosidérose marginale du névraxe d'évolution favorable sous corticoïdes.

INTRODUCTION: Superficial siderosis is of the Central Nervous System (CNS) is an uncommon and often disabling disorder. There is no evidence that any treatment, including removal of an identified source of bleeding, affects disease progression. OBSERVATION: We report the case of a 49-year-old woman exhibiting progressive and various neurological disorders associating chorea, pyramidal syndrome, cerebellar ataxia, cognitive disorders and cranial nerve deficits. She had a prior history of right occipital arterioveinous malformation (AVM) revealed four years before by ventricular hemorrhage. The AVM was treated by radiosurgery. Because of a pronounced progression of the symptoms, treatment with steroid therapy was initiated before the diagnosis of siderosis of the central nervous system was asserted by magnetic resonance imaging (rim of hypo-intensity due to hemosiderin around the brainstem, the cerebellum and the spinal cord on T-2 weighted and gradient echo T-2* imaging) and cerebrospinal fluid (CSF) examination (high CSF levels of iron and ferritin). Over the next months the neurological condition improved under steroid therapy. CONCLUSION: Our observation is interesting because of the chorea movement disorders which are rarely reported in the disease and because of the improvement of the neurological condition after steroid therapy which is described in only another case in the literature. Steroid therapy could constitute a new track for the treatment of siderosis of CNS.

[Interest of the ketogenic diet in a refractory status epilepticus in adults]. / Intérêt du régime cétogène dans le traitement d'un état de mal épileptique résistant de l'adulte.

INTRODUCTION: Ketogenic diets have been employed for the treatment of intractable epilepsy in children since 1921, although underlying mechanism remains unknown. OBSERVATION: We report the case of a 54-year-old man with partial refractory status epilepticus who exhibited a favourable outcome about seven days after introduction of a ketogenic diet in association with antiepileptic drugs. DISCUSSION: Although its efficiency was largely demonstrated in children, little is known about the impact of a ketogenic diet in adults with refractory epilepsy. CONCLUSION: Introduction of a ketogenic diet requires a multidisciplinary approach. Its usefulness in adult intractable epilepsy and/or refractory status epilepticus merits further study into its efficacy in reducing the frequency of seizures and a possible prolonged effect.

High erythropoietin and low vascular endothelial growth factor levels in cerebrospinal fluid from hypoxemic ALS patients suggest an abnormal response to hypoxia.

Animal studies have highlighted the potentially neuroprotective role of vascular endothelial growth factor (VEGF). Low levels of this growth factor have been found in the cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS). VEGF (and other proteins, such as erythropoietin (EPO)) are produced in response to hypoxia via a common pathway involving a specific transcription factor (hypoxia-inducible factor, HIF) and a hypoxia responsive element (HRE) in the respective genes' promoter regions. In this study, we report finding the expected, high levels of VEGF and EPO in CSF from hypoxemic neurological controls, whereas EPO (but not VEGF) levels are high in the CSF from hypoxemic ALS patients. Hence, the VEGF levels in CSF from patients with ALS were significantly lower than those seen in hypoxemic controls. There was a trend towards higher CSF levels of EPO in hypoxemic ALS patients than in hypoxemic controls. Our results suggest that VEGF may not be produced in sufficient amounts in chronically hypoxic ALS patients and that this dysfunction may participate in the pathogenesis of the disease. The high EPO levels in hypoxemic ALS patients nevertheless suggest an intact common oxygen-sensor pathway.

Improvement of gait by chronic, high doses of methylphenidate in patients with advanced Parkinson's disease.

BACKGROUND: Therapeutic management of gait disorders in patients with advanced Parkinson's disease (PD) can sometimes be disappointing, since dopaminergic drug treatments and subthalamic nucleus (STN) stimulation are more effective for limb-related parkinsonian signs than for gait disorders. Gait disorders could also be partly related to norepinephrine system impairment, and the pharmacological modulation of both dopamine and norepinephrine pathways could potentially improve the symptomatology. AIM: To assess the clinical value of chronic, high doses of methylphenidate (MPD) in patients with PD having gait disorders, despite their use of optimal dopaminergic doses and STN stimulation parameters. METHODS: Efficacy was blindly assessed on video for 17 patients in the absence of L-dopa and again after acute administration of the drug, both before and after a 3-month course of MPD, using a Stand-Walk-Sit (SWS) Test, the Tinetti Scale, the Unified Parkinson's Disease Rating Scale (UPDRS) part III score and the Dyskinesia Rating Scale. RESULTS: An improvement was observed in the number of steps and time in the SWS Test, the number of freezing episodes, the Tinetti Scale score and the UPDRS part III score in the absence of L-dopa after 3 months of taking MPD. The L-dopa-induced improvement in these various scores was also stronger after the 3-month course of MPD than before. The Epworth Sleepiness Scale score fell dramatically in all patients. No significant induction of adverse effects was found. INTERPRETATION: Chronic, high doses of MPD improved gait and motor symptoms in the absence of L-dopa and increased the intensity of response of these symptoms to L-dopa in a population with advanced PD.

Sleep and vigilance in corticobasal degeneration: a descriptive study.

INTRODUCTION: Sleep disorders are common in extrapyramidal diseases, but have rarely been demonstrated in corticobasal degeneration (CBD). METHODS: Here, we describe sleep and vigilance in five consecutive patients with CBD. RESULTS: All five patients had insomnia, four displayed periodic limb movements during sleep (PLMS) and/or restless leg syndrome (RLS), and two had sleep respiratory disorders. None had REM sleep behaviour disorders or excessive daytime sleepiness. CONCLUSIONS: Polysomnography is useful for diagnosing treatable sleep disorders in CBD.