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Introduction: Currently we have no precise data on the parkinsonian syndromes in Madagascar. This study aims to collect data on these diseases and to describe the frequency and the clinical profile of parkinsonian syndromes in our Department of Neurology., Methods: We conducted a retrospective and descriptive study in the Department of Neurology, in Befelatanana from January 2014 to June 2018. The demographic and clinical data of patients diagnosed as having a parkinsonian syndrome were collected. We assessed data rates and characteristics and then we compared patients with idiopathic Parkinson's disease and patients with other parkinsonian syndromes. Data were processed using R. software., Results: The study included 104 of 3528 patients, seen in our Department. Among the patients with parkinsonian syndrome, 67(64.42%) had idiopathic Parkinson's disease (PD) and 37 (35.47%) another parkinsonian syndrome. The average interval between the onset of the disease and the consultation or the hospitalization in the Department was 2.5 years. For MP, the median age at onset was 58.5 [23; 80] years, the median age at diagnosis was 62 [28; 83] years and the sex ratio were 1.97. The median Hoehn and Yahr score were 2.0. Tremor-dominant Parkinson's disease was found in 24 (35.42%) of cases, a mixed phenotype was found in 28 (41.71%) of cases while akineto-rigid Parkinson's disease was found in 15 (22.38%) of cases. The other parkinsonian syndromes ocuurred in 27 (72.97%) men, with a median age at onset of 57.5 [26; 83] years, a median age at diagnosis of 59.3 [26; 83] years. Etiologies were dominated by Multiple System Atrophy 17/37 (46.64%). Patients with other parkinsonian syndromes had several cognitive disorders (p=0,0306) and MPs were more sensitive to dopamine (p=0.006)., Conclusion: The patients with idiopathic parkinsonian syndrome had features different from those of patients with parkinsonism. There was a diagnostic delay as in other developing countries., Competing Interests: Les auteurs ne déclarent aucun conflit d’intérêts., (© Nomena Finiavana Rasaholiarison et al.)

Competing Interests: J.-P. Azulay déclare avoir participé à des liens ponctuels avec Acadia, Roche, AbbVie, Teva, Adamas, Pfizer et Neuroderm (essais cliniques), avec Zambon, AbbVie et VCB (conseils, formations) et avoir été pris en charge lors de congrès par AbbVie, Orkyn, Medtronic, Zambon.

In Parkinson's disease, motor signs have long been the main targets of the management of the disease. In recent years, non-motor disorders have elicited increasing interest. These disorders are under diagnosed and managed more difficultly than motor signs and are sometimes perceived as more disturbing by the patients. These signs are polymorphous, sometimes occurring before the motor symptoms but increase with the disease duration and complicating always the late stages. They may fluctuate as the motor signs, while being under the control of dopaminergic pathways, or be linked to the degeneration of other neuronal circuits. These clinical manifestations, whether or not fluctuating are classified into three major categories: psycho-cognitive including sleep disorders, autonomic and sensory., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

The past 20 years has witnessed tremendous progress in our understanding of Parkinson's disease. It is now well established that α-synuclein, a presynaptic neuronal protein, is not only a marker but also an actor of the disease. In this review, we discuss the advances that have been obtained in neuropathology using α-synuclein immunohistochemistry and the role of this protein in the spread of the disease., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Parkinsonian syndrome is the clinical expression of a lesion within the nigro-striatal dopaminergic pathway. Akinesia is the main manifestation of parkinsonism. The clinical analysis of motor symptoms may guide clinical diagnosis. Parkinson's disease is characterized by a pure asymmetric parkinsonian syndrome, responsive to dopaminergic treatment. The evolution of Parkinson's disease is characterized by the occurrence of motor complications (dyskinesia and fluctuations). Gait disturbances (postural instability and freezing) are late in Parkinson's disease. When early (within the first three years), they point to atypical parkinsonian syndrome., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Parkinson's disease (PD) is a frequent and complex progressive neurological disorder that increases in incidence with age. Although historically PD has been characterized by the presence of progressive dopaminergic neuronal loss of the substantia nigra, the disease process also involves neurotransmitters other that dopamine and regions of the nervous system outside the basal ganglia. Its clinical presentation in elderly subjects differs from that in younger subjects, with more rapid progression, less frequent tremor, more pronounced axial signs, more frequent non-motor signs linked to concomitant degeneration of non-dopaminergic systems, and more frequent associated lesions. Despite the high prevalence of PD in elderly subjects, few therapeutic trials have been conducted in geriatric patients. Nevertheless, to improve functional disability while ensuring drug tolerance, the principles of optimized and multidisciplinary clinical management have to be known. The aim of this review is to provide an update on clinical and therapeutic features of PD specifically observed in elderly subjects., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Recently awarded by the prestigious Lasker Foundation, high-frequency deep brain stimulation (DBS) has been used for the first time in 1987 in tremor and in 1993 in Parkinson's disease (PD) by the Grenoble group. So far, over 100 000 patients have been operated on worldwide. In PD, DBS induces an almost complete abatement of tremor, motor fluctuations and dyskinesias along with a reduction in levodopa dose. Although its mechanism of action is not fully understood, DBS would inhibit or modulate the expression of abnormal neuronal networks associated with given symptoms. It is therefore expected that DBS will extend to other severe neurological and psychiatric disorders. Furthermore, technological advances of the procedure are ongoing to optimize final outcomes.

Movement disorders such as Parkinson's disease (PD), essential tremor (ET) and dystonia can benefit from deep brain stimulation (DBS). DBS is considered when symptoms are disabling despite optimal medical therapy. Contraindications include dementia, uncontrolled psychiatric disease and/or comorbid conditions with potential for evolution. Targets are the subthalamic nucleus for PD, the ventral intermediate nucleus for ET and the globus pallidus internus for dystonia. The beneficial effet of DBS has been well documented for symptom control. Optimal target localization of the electrodes reduces the occurrence of side-effects. Stimulation-induced adverse effects can usually be abolished by turning the stimulation off, changing the active contact or other stimulation parameters.

Parkinson's disease (PD) is a major socio-economic burden increasing with the aging population. In advanced PD, the emergence of symptoms refractory to conventional therapy poses a therapeutic challenge. The success of deep brain stimulation (DBS) and advances in the understanding of the pathophysiology of PD have raised interest in non-invasive brain stimulation (NIBS) as an alternative therapeutic tool. NIBS could offer an alternative approach for patients at risk who are excluded from surgery and/or to treat refractory symptoms. The treatment of the freezing of gait, a major cause of disability and falls in PD patients, could be enhanced by transcranial direct current stimulation (tDCS). A therapeutic study is currently performed at the Department of Neurology at the CHUV.

Olfaction is a complex sensory system, and increasing interest is being shown in the link between olfaction and cognition, notably in the elderly. In this literature review, we revisit the specific neurophysiological features of the olfactory system and odorants that lead to a durable olfactory memory and an emotional memory, for which the implicit component produces subconscious olfactory conditioning. Olfaction is known to affect cognitive abilities and mood. We also consider the impairment of olfactory function due to ageing and to neurodegenerative diseases, in particular Alzheimer's disease and Parkinson's disease, through anatomopathological changes in the peripheral and central olfactory structures. The high frequency of these olfactory disorders as well as their early occurrence in Alzheimer disease and Parkinson disease are in favour of their clinical detection in subjects suffering from these two neurodegenerative diseases. Finally, we analyse the impact of olfactory stimulation on cognitive performance and attention. Current observational data from studies in elderly patients with Alzheimer-type dementia are limited to multiple sensory stimulation methods, such as the Snoezelen method, and aromatherapy. These therapies have shown benefits for dementia-related mood and behaviour disorders in the short term, with few side effects. Since olfactory chemosensory stimulation may be beneficial, it may be proposed in patients with dementia, especially Alzheimer-type dementia, as a complementary or even alternative therapy to existing medical strategies., (Copyright © 2014 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Voice and speech impairments are frequent in Parkinson's disease, particularly when the disease is at an advanced stage. These impairments affect spoken communication and may become a serious disability for someone with Parkinson's disease. Many studies based on auditory-perceptual or acoustic methods have been carried out to characterize dysarthria. The heterogeneity of evaluation methods and experimental bias however make results difficult to understand. For instance, in terms of phonatory impairments and with regard to F0, results are contradictory: PD speech may be characterized by either higher F0 or lower F0 compared to control subjects, or there may be no difference at all between the two population. In this study, we aim to provide a conceptual and methodological framework which allows for interpreting the results obtained from 44 speakers (29 PD and 15 control subjects) in relation to physiological (gender, age, PD subjects' pharmacologic state) and linguistic (speech production tasks) constraints. For the present corpus, we did not observe any F0 mean difference between the two groups. Our results however reveal a significant increase in F0 mean in PD subjects under L-dopa. We assume a double and opposite effect on F0 mean during drug withdrawal: low sub-glottal pressure, due to PD, results in a decrease in F0, while laryngeal rigidity leads to an increase in F0. These two effects thus mutually annihilate. Under L-Dopa, however, the drug effect increases sub-glottal pressure, which combined with an increase in F0 due to rigidity, leads to a global increase in F0.

Although the diagnosis of Parkinson disease is based on motor symptoms, it is now well known that non-motor symptoms are an integral part of this pathology, involving in fact multiple systems. These non-motor symptoms affect large population of patients and can appear sometimes before the motor disorders. The non-motor symptoms include mainly neuropsychological difficulties, neuropsychiatric symptoms, and autonomic disorders, but involve also pain and sleep disturbances for example. Depression may occur at any stage of the disease, and consists in major depressive disorder, minor depressive disorder, and dysthymia. During the course of the disease, 50% of patients experience anxiety. Apathy is present in up to 30-40% of patients, due to loss of motivation, appearing in emotional, intellectual and behavioral domains. Dopamine dysregulation syndrome and impulse control disorders are not rare, and in relation with dopaminergic therapies. Impulse control disorders include pathological gambling, hyper sexuality, compulsive shopping, and eating disorder. Visual hallucinations can occur in 30% of patients, mostly induced by dopaminergic therapies. Often, they have deeper impact on the quality of life than the motor symptoms themselves, which stay the focus of attention during consulting. Identifying those can help in providing better care with a positive impact on the quality of life of the patients.

Decision making is a complex ability that is likely to be damaged in numerous psychiatric and neurologic disorders and also during the aging process. It therefore implies a large interconnection of cortical and subcortical structures that are directly impacted by the neuroanatomical and neurochemical modifications that occur during the usual or the pathologic aging. Two decision modalities have been isolated, depending on whether the decision making is performed under explicit knowledge of the risks taken or not. In the first case, the decision is taken based on success probabilities and also as a result of preliminary reinforcements (decision under risk). This modality is linked to the executive functions and its neural substrate would be the cognitive frontal striatal loops. In the second case, the decision is exclusively based on preliminary reinforcements (decision under ambiguity) and would be partially independent of cognitive functions. Its neural substrate would be the limbic frontal striatal loops. Nevertheless, the comparison of these hypothesis with the clinical data raises a certain number of controversies. Only the decision making under ambiguity appears to be responsive to the effects of usual aging, suggesting there would be a premature aging of the limbic loops. In Parkinson's disease, controversies appear to know whether the primitive decision impairment concerns the modality under risk or the one under ambiguity, as well as the question of the frontal striatal loops primitively damaged in this pathology pending. Furthermore, the cortical neurodegenerative diseases seem to demonstrate that the decision under ambiguity may be impacted by the cognitive functions, challenging the assumed independency between these two processes. On basis of some studies, the authors suggest to reconsider the links between the decision making, in particular the under ambiguity one and the cognitive functions, questioning how executive functions contribute to this decision modality.

Autonomic nervous system (ANS) modulates the function of all body organs through both parasympathetic and sympathetic fibers. Orthostatic hypotension is frequently observed in the course of central nervous system diseases including cortical (stroke, epilepsy, dementias), neurodegenerative (Parkinson's disease, multisystem atrophies) and spinal cord diseases. In some cases, the mechanism of orthostatic hypotension associated with central nervous system diseases involves a dysfunction of peripheral ANS fibers., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

The subthalamic nucleus deep-brain stimulation Parkinson's disease patient model seems to represent a unique opportunity for studying the functional role of the basal ganglia and notably the subthalamic nucleus in human emotional processing. Indeed, in addition to constituting a therapeutic advance for severely disabled Parkinson's disease patients, deep brain stimulation is a technique, which selectively modulates the activity of focal structures targeted by surgery. There is growing evidence of a link between emotional impairments and deep-brain stimulation of the subthalamic nucleus. In this context, according to the definition of emotional processing exposed in the companion paper available in this issue, the aim of the present review will consist in providing a synopsis of the studies that investigated the emotional disturbances observed in subthalamic nucleus deep brain stimulation Parkinson's disease patients. This review leads to the conclusion that several emotional components would be disrupted after subthalamic nucleus deep brain stimulation in Parkinson's disease: subjective feeling, neurophysiological activation, and motor expression. Finally, after a description of the limitations of this study model, we discuss the functional role of the subthalamic nucleus (and the striato-thalamo-cortical circuits in which it is involved) in emotional processing. It seems reasonable to conclude that the striato-thalamo-cortical circuits are indeed involved in emotional processing and that the subthalamic nucleus plays a central in role the human emotional architecture., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Parkinson's disease is mainly considered as a motor disorder defined by a motor triad. However, various non-motor manifestations may be encountered in Parkinson's disease, including hyposmia, pain, fatigue, sleep disorders, cognitive and behavioral disorders. The pathophysiology of these signs is complex, not univocal and remains poorly understood. Functional imaging techniques either by positron emission tomography, single photon emission tomography or functional magnetic resonance imaging provide an invaluable opportunity to better understand the pathophysiology of these signs. In this paper, we present a review of the recent advances provided by functional imaging in this area., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Parkinson's disease provides a useful model for studying the neural substrates of emotional processing. The striato-thalamo-cortical circuits, like the mesolimbic dopamine system that modulates their function, are thought to be involved in emotional processing. As Parkinson's disease is histopathologically characterized by the selective, progressive and chronic degeneration of the nigrostriatal and mesocorticolimbic dopamine systems, it can therefore serve as a model for assessing the functional role of these circuits in humans. In the present review, after a definition of emotional processing from a multicomponential perspective, a synopsis of the emotional disturbances observed in Parkinson's disease is proposed. Note that the studies on the affective consequences of subthalamic nucleus deep brain stimulation in Parkinson's disease were excluded from this review because the subject of a companion paper in this issue. This review leads to the conclusion that several emotional components would be disrupted in Parkinson's disease: subjective feeling, neurophysiological activation, and motor expression. We then discuss the functional roles of the striato-thalamo-cortical and mesolimbic circuits, ending with the conclusion that both these pathways are indeed involved in emotional processing., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Apathy is a loss of motivation compared to the previous level of functioning of the subject. It affects the subject's behavior, cognition and emotional state. It is one of the main behavioral manifestations of Parkinson's disease. Although it may be a symptom of depression, it often exists as an isolated syndrome in Parkinson's disease patients. Apathy is usually not related to the severity of the motor symptoms, but frequently associated with the severity of cognitive impairment. Apathy is also a possible complication of treatment by stimulation of the subthalamic nucleus. Screening and assessment of apathy require the use of specific tools, some of which are validated in Parkinson's disease. From a pathophysiological point of view, apathy results from a dysfunction of the limbic circuit connecting the ventral striatum to orbitofrontal and anterior cingulate cortex. The dopaminergic denervation in these regions seems to play a key role, but other mechanisms are probably involved. Further studies are warranted to progress in the therapeutic management of this invalidating syndrome., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

It has become increasingly evident over the last years that Parkinson's disease is a multicentric neurodegenerative disease that affects several neuronal structures outside the substantia nigra, among which is the enteric nervous system. The aims of the present article are to discuss the role of the enteric nervous system lesions in pathology spreading (Braak's hypothesis) and in the gastrointestinal dysfunction encountered in Parkinson's disease. Owing to its accessibility to biopsies, we further discuss the use of the enteric nervous system as an original source of biomarker in Parkinson's disease., (Copyright © 2012 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Introduction: Voluntary or reactive saccades predominate in rapid eye movements. Their goal is to preserve an active and optimal visual perception of the environment. Saccades cannot be guided once launched. Oculomotor plasticity, or saccadic adaptation, is still partially unknown, in particular the role played by the basal ganglia. New neuro-ophthalmological rehabilitation techniques require understanding the neurophysiological basis and demonstrating the neuronal structures involved in this plasticity., Objectives: This study assessed the reactive saccade adaptation in patients with idiopathic Parkinson disease, as a model of basal ganglia dysfunction. We predicted that saccadic adaptation would be preserved in this pathology., Patients and Methods: Five patients with mild idiopathic hemi-Parkinson disease were included, as well as four age-matched controls. Reactive saccade adaptation was studied using the double-step target paradigm, in patients with OFF-Dopa treatment and in controls., Results: Group analysis demonstrated that patients had a lower level of adaptation than the controls (p<0.05). Individually, two patients did not adapt for bilateral saccades and one for ipsilateral (compared to Parkinson motor clinical syndrome) saccades. Two additional patients adapted on both sides but with a deficit in contralateral saccades when compared to the control group., Discussion: These preliminary results suggest basal ganglia involvement in reactive saccadic adaptation, which remains to be clarified., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Objective: The purpose of this review is to draw up a statement on current knowledge available on perioperative management of Parkinson's disease patients., Study Design: Review., Data Synthesis: In France, approximately 150,000 persons suffer from Parkinson's disease, a neurodegenerative disorder of central nervous system. Parkinson's disease results in selective and irreversible loss of dopaminergic neurons in the substantia nigra pars compacta. Medications based on dopaminergic drugs are used to control motor symptoms and improve motor function. Development of surgical approach, especially deep brain stimulation, has revolutionized the medical management of many patients with Parkinson's disease. Anesthesia of these patients remains a challenge for the clinician. The aim of this review is to describe anaesthetic considerations of patients with Parkinson's disease and to discuss management of antiparkinsonians medications during the perioperative period., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Dopamine replacement therapy in Parkinson's disease (PD) improves the motor symptoms. However, it has recently been shown that a small sub-group of patients suffers from motor and behavioral disturbances associated with the use of dopamine agonists (DAs). The behavioral disorders are incentive- or reward-based repetitive symptoms regrouped under the term « dopamine dysregulation syndrome » (DDS). They include pathological gambling, hypersexuality, compulsive shopping, compulsive eating, punding, and compulsive medication use. Whether these behaviors are related to the dopaminergic medications interacting with an underlying individual vulnerability or whether the primary pathological features of Parkinson's disease play a role is not entirely understood. This review is devoted to the phenomenology of the DDS and factors influencing its susceptibility. We further review the literature studies that investigated the decision-making profile using the Iowa Gambling Task in Parkinson's disease, and the recent literature devoted to these abnormal behaviors in the restless legs syndrome (RLS). Given the potential substantial impact of the DDS on personal, familial, social, and financial well-being, patients with PD or RLS should be informed that DAs use may lead to the development of impulsive and compulsive disorders, and clinicians should include the investigation of these disorders as part of routine clinical care. The refinement of clinical strategies to predict, identify and manage DDS will help the future care of motor and non-motor symptoms of Parkinson's disease.

Objective: to assess the sexual function in men with idiopathic Parkinson's disease., Patients and Methods: a cross-sectional study was performed in 35 men, mean age 68 ± 9 years, with idiopathic Parkinson's disease followed in a single urological department. The 15 questions International Index of the Erectile Function was sent by postal mail., Results: the answer's rate was 42.9% (15 patients). The mean age of the responders was 68.7 ± 10.0 years. Mean duration of the disease was 10.4 ± 6.8 years. Sexual dysfunction was the second cause for consultation in urology. Despite a sustained sexual desire, patients had an altered sexual function with low erectile function, orgasmic function, intercourse satisfaction and total satisfaction scores. According to the Cappelleri's classification, the erectile dysfunction was severe in 54% of the cases and moderate in 26.6%. Age, institutionalization and overactive bladder symptoms were associated with erectile, orgasmic function and intercourse satisfaction alteration, sexual desire alteration, intercourse and global satisfaction alteration, respectively., Conclusion: men with idiopathic Parkinson's disease had a severe sexual dysfunction. The sexual desire was usually maintained but all the other domains were severely altered., (2010 Elsevier Masson SAS. All rights reserved.)

It has become increasingly evident over the past years that the pathological process in Parkinson's disease extends well beyond the substantia nigra and involves non-dopaminergic neurotransmitter systems that mediate motor and non-motor symptoms. In this article, both the pathophysiology and the pharmacological management of these non-dopaminergic symptoms are discussed., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

The diagnosis of Parkinson's disease (PD) requires ruling out other causes of parkinsonism. Among various "other" causes of parkinsonism, neurodegenerative causes or "atypical parkinsonism" are the most difficult to diagnose. Most common diseases are "synucleinopathies": multiple system atrophy and dementia with Lewy bodies and "tauopathies": progressive supranuclear palsy and corticobasal degeneration. Unexpected or atypical signs and symptoms for PD, also called "red flags" along with absent or poor or short-lived levodopa response may be a clue for the diagnosis. Some tests may also support the diagnosis, among them, structural (MRI) and functional brain imaging, autonomic function tests and urodynamics, oculographic recordings and neuropsychological work-up, are the most useful., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Considerable progress has been made in the pathophysiology of Parkinson's disease in the last 25 years. To better understand the nature and diversity of the symptoms of Parkinson's disease it is necessary to integrate clinical knowledge on 1) the role of dopamine, 2) the anatomical and functional organization of the basal ganglia, and 3) the dysfunctions observed in MPTP-treated monkeys. This article reviews the principal discoveries in these three research fields and their contribution to our understanding of the pathophysiology of Parkinson's disease.

Introduction: Gait and balance often change with age. Few studies are available on gait analysis in the elderly. In our work, we have focused on slow walking and variation in pace. Since first introduced by Lundlin, the dual-task paradigm has been largely used to test for the risk of falls and to better understand the link between mild cognitive decline and variation in gait. To our knowledge, very few clinical data are available on the gait changes observed in the elderly in the dual-task situation. In this study, we compared changes in gait and balance between the simple task and the dual-task situation in a 10-m walk test conducted in community-dwelling old people., Methods: Eighty-nine subjects attending a geriatric outpatient clinic (age 80.76+/-2.82 years) were included in our protocol. Gait, balance and posture were systematically evaluated during a simple and dual-task 10-m walk using a specific 11-item clinical scale. Gait speed was noted., Results: Few differences were found in the dual-task walk, only reduced speed, more stops during the walk and less compliance with instructions. These results were correlated with the Mini Mental Status (MMS) score. Systematic clinical analysis failed to identify any links with age, the MMS, the UPDRS, the Tinetti scale or gait speed except for the variables freezing, increased sustention polygon and ataxia., Discussion: This kind of study appears to offer an attractive analytical approach but would require a more pertinent choice of variables for cognitive evaluation and a more exhaustive set of MRI criteria. Nonetheless, clinical gait analysis could improve our understanding of the consequences of mild cognitive impairment and aging., (Copyright (c) 2009 Elsevier Masson SAS. All rights reserved.)

Introduction: Gait disorders and freezing of gait (FOG) are seen in most patients with advanced Parkinson disease. Response to levodopa and deep brain stimulation is variable across patients., State of Art: Thalamic stimulation is ineffective on gait and can even worsen balance when bilaterally applied. Pallidal stimulation moderately improves gait disorders and FOG although this effect tends to wane after three to five years. Stimulation of the subthalamic nucleus (STN) improves levodopa-responsive gait disorders and FOG. However, some patients worsen after STN stimulation and others are better improved under levodopa than under STN stimulation. Synergistic effects of the two treatments have been reported. As for pallidal stimulation, there is a failure of long-term STN stimulation to improve gait, probably due to the involvement of non-dopaminergic pathways as the disease progresses. Levodopa-resistant gait disorders and FOG do not usually benefit from STN stimulation. In the rare cases of levodopa-induced FOG, STN stimulation may be indirectly effective, as it enables reduction or arrest of the levodopa treatment., Perspectives: Pedunculopontine nucleus stimulation has recently been performed in small groups of patients with disabling gait disorders and FOG. Although encouraging, the first results need to be confirmed by controlled studies involving larger series of patients., Conclusions: Overall, gait disorders remain a motor PD symptom that is little improved, or only temporarily, by current pharmacological and surgical treatments. Patient management is complex., (Copyright 2009 Elsevier Masson SAS. All rights reserved.)

Despite the fact that the neurotransmitter dopamine was discovered more than 50 years ago, we still have limited knowledge of its physiological and pathological roles. Recent work has unveiled novel and surprising properties of dopamine neurons and of other key players involved in regulating the dopamine system. For example, the integration of the dopamine signal by its receptors depends on many proteins of diverse signaling pathways and also of other types of receptors that interact with and regulate dopamine receptors: many new promising interactions have been reported during the past few years. Also, we are beginning to discover that chronic treatment with dopamine receptor ligands or other molecules affecting dopaminergic pathways induce long-term molecular, structural and functional rearrangements that could ultimately force us to revisit the mechanism of action of established therapeutic agents. Finally, the discovery of glutamate co-release by dopamine neurons is leading us to reconsider some keys aspects of dopamine neuron physiology.

Gait disorders form part of the axial symptoms observed in Parkinson's disease (PD) and also represent a major source of therapeutic failure in the later stages of PD, with the appearance of freezing of gait (FOG) and falls. Double-blind clinical trials and, above all, clinical experience have demonstrated that l-DOPA is effective in reducing FOG. Dopaminergic agonists appear to be less effective than l-DOPA and lack formal proof of their efficacy. The enzyme inhibitors provide modest benefits, which need to be confirmed. Hence, these symptoms appear to be partially doparesistant and justify investigation of other major neurotransmission systems. Of the various drugs with partial noradrenergic activity, methylphenidate may improve FOG and attention disorders. Memantine has shown some value in improving motor symptoms and gait in fluctuating parkinsonian patients - possibly by reducing the effect of glutamatergic hyperactivation of the subthalamic nucleus on the pedunculopontine nucleus (PPN). The PPN's dense cholinergic innervation also suggests that cholinesterase inhibitors may be of use, although any benefits must be set against a potential aggravation of rest tremor. The many interactions between the serotoninergic and dopaminergic systems require the implementation of clinical studies on the complex motor impact of serotoninergic treatments, which may aggravate the parkinsonian syndrome while improving gait (as is the case with paroxetine and ritanserin). This review seeks to develop the various pathophysiological hypotheses prompted by the results of fundamental studies and pilot clinical trials, with a view to justifying the implementation of confirmatory, double-blind, placebo-controlled therapeutic trials., (Copyright 2009 Elsevier Masson SAS. All rights reserved.)

Parkinson's disease is a frequent and major source of motor disability, for which physical therapies currently involve less than a third of ambulatory patients and are thus underutilized when compared to chemical and surgical treatments. However, dopaminergic therapies alone prove unable to prevent worsening of motor disability after a number of years. There is rising interest about physical neurorehabilitative therapy for Parkinson's disease, for its symptomatic therapeutic properties, but also for its potential neuroprotective effects in the light of compelling, recent animal literature. The approach to therapy in an individual patient may be governed at the most basic level by the disease stage. For moderate stages of Parkinson's disease (ambulatory patients who have retained a certain degree of physical independence), therapy may focus on the teaching of exercises to the patient: strategies established in controlled studies when used over few weeks periods include motor strengthening programs in the lower limb, high intensity aerobic exercises, attentional strategies using in particular verbal instruction sets, sensory cueing, active axial rotation exercises and high-number repetition of specific tasks. A randomized protocol will soon evaluate the concept of asymmetric motor training, combining a strengthening program in extensor, abductor, external rotator and supinator muscles and a stretching program in their antagonists. For advanced stages (individuals with compromised sit-to-stand, ambulation and significant disability), the therapeutic focus may shift to the teaching of compensation strategies to the patient and the caregiver, both to lessen the effects of motor impairment and to optimize safety. A number of these compensatory strategies are reviewed, some being validated in controlled protocols. In idiopathic Parkinson's disease, clinicians must continue evaluating the symptomatic and perhaps neuroprotective value of physical treatment strategies used over the long term. In atypical parkinsonism, physical treatments often remain the only realistic methods to improve motor behavior and reduce functional deficiencies. The relatively short duration of the effects of physical therapies implies that such programs be pursued over long periods of time, or repeated frequently, for their benefits to be maintained over time., (Copyright 2010 Elsevier Masson SAS. All rights reserved.)

Gait disorders and axial symptoms are the main therapeutic challenges in advanced Parkinson's disease (PD). Gait disorders in PD are characterized by spatial and temporal dysfunction. Gait hypokinesia is the first to appear and is responsible for the decrease in velocity. A good sensitivity to the levodopa is well established. Morris et al. [Morris ME, Iansek R, Matyas TA, Summers JJ. Ability to modulate walking cadence remains intact in Parkinson's disease. J Neurol Neurosurg Psychiatry 1994a;57(12):1532-4; Morris ME, Iansek R, Matyas TA, Summers JJ. The pathogenesis of gait hypokinesia in Parkinson's disease. Brain 1994b;117(Pt. 5):1169-81; Morris ME, Iansek R, Matyas TA, Summers JJ. Stride length regulation in Parkinson's disease. Brain 1996;119:551-68] demonstrated that the ability to modulate walking cadence remains intact in PD, and could correspond to a compensatory mechanism. More advanced disease stages of the disease are characterized by abnormal temporal parameters (such as stride length variability, stride time variability and cadence elevation) which are unresponsive to levodopa therapy and may be correlated with the occurrence of falls and freezing of gait (FOG). Lastly, postural instability also results in falls and is poorly responsive to levodopa. A link between gait impairment and frontal disorders has recently been suggested. After a few years of evolution, paradoxical episodic phenomena are described: festination ("hastening gait" with rapid small, short steps) and FOG (involuntary and sudden cessation of gait). Both symptoms are often incapacitating for PD patients, because of their resultant loss of independence and their poor response to levodopa therapy. Kinematical studies of FOG revealed a decrease in velocity, stride length and an exponential increase in cadence, prior to a FOG episode. New approaches (functional MRI, wavelets...) should offer new perspectives concerning these disabling symptoms., (Copyright 2010. Published by Elsevier Masson SAS.)

Introduction: Parkinsonian dysarthria can alter oral communication of the patients in the long-term. Subthalamic nucleus (STN) stimulation represents an interesting therapeutic option, although it does not seem to improve axial signs, of which dysarthric speech. The objective of our study was to contribute to the evaluation of STN stimulation effects on speech impairment and in particular on pneumophonic coordination: this latter parameter can be assessed indirectly by evaluating the temporal progression of the intraoral pressure (IOP) during the expiratory phase; thus, IOP represents the transient expression of subglottal pressure (SGP)., Patients and Method: Using a dedicated system (EVA2), 20 parkinsonian patients were recorded in ON and OFF STN stimulation conditions in order to evaluate IOP on three measurement points (2nd, 4th and 6th consonants P) during realization of the sentence "Papa ne m'a pas parlé de beau-papa" ("Daddy did not speak to me about daddy-in-law") which corresponds to a breath group. Eleven control subjects were recorded in parallel in order to define reference measurements., Results: STN stimulation improved significantly IOP at the level of the initial measurement points (2nd P and 4th P), with an effect of convergence at the level of the third point (6th P) where the difference between OFF and ON STIM conditions was not significant any more. In addition, the performance of the patients ON STIM remained much lower than that of the control subjects., Conclusion: Our results raise the significant concept that IOP measurement can be regarded as a relevant indicator for dysarthria in Parkinson's disease. They also show that the improvement of pneumophonic coordination by STN stimulation is restricted to the initial period of the expiratory phase, confirming again the mitigated and controversial effect of STN stimulation on axial signs.

Purpose: Quality of life (QoL) in multiple system atrophy (MSA) is thought to be poorer than in Parkinson's disease (PD), primarily because of motor impairment, autonomic dysfunction and depression. The aim of the study was to investigate QoL in 10 patients with probable MSA (parkinsonian subtype) compared with 10 PD patients matched for motor disability on UPDRS III motor score., Methods: All patients were ambulatory and non-demented. Mean durations of disease in MSA and PD patients were respectively 3.6 and 9.0 years. QoL was assessed using the SF-36 health-related questionnaire and a life satisfaction visual analogue scale. Patients were also evaluated for cognitive function (Mattis Dementia Rating Scale [Mattis DRS], Wisconsin Card Sorting Test [WCST], Stroop, Fluencies), depression (Beck Depression Inventory-II [BDI-II]), apathy (Modified Apathy Evaluation Scale) and were screened for non-motor symptoms (NMS Quest)., Results: The only difference in QoL between MSA and PD patients matched for motor disability was that the SF-36 vitality subscore was more impaired in MSA and negatively correlated with interference index on Stroop word colour testing. Depression and non-motor symptoms were associated with poorer QoL in both groups. Among MSA patients, cognitive impairment (Stroop interference index) and apathy also had a negative impact., Conclusion: There was no major difference in QoL between MSA and PD patients matched for motor disability with a disease duration about 5 years longer. The SF-36 vitality subscore was more impaired in MSA and associated with interference sensitivity.

Post-translational protein modifications play essential roles in many aspects of cellular functions and therefore in the maintenance of cell integrity. These protein modifications are involved at all stages of neuronal communication within the central nervous system. Sumoylation is a reversible post-translational protein modification that consists in the covalent labelling of a small protein called SUMO to lysine residues of selected target proteins. Sumoylation is a well characterized regulator of nuclear functions and has recently emerged as a key factor for numerous extranuclear processes. Furthermore, sumoylation has recently been shown to modulate synaptic transmission and is also implicated in a wide range of neurodegenerative diseases.