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IMPORTANCE Collective evidence has strongly suggested that deep brain stimulation (DBS) is a promising therapy for Tourette syndrome. OBJECTIVE To assess the efficacy and safety of DBS in a multinational cohort of patients with Tourette syndrome. DESIGN, SETTING, AND PARTICIPANTS The prospective International Deep Brain Stimulation Database and Registry included 185 patients with medically refractory Tourette syndrome who underwent DBS implantation from January 1, 2012, to December 31, 2016, at 31 institutions in 10 countries worldwide. EXPOSURES Patients with medically refractory symptoms received DBS implantation in the centromedian thalamic region (93 of 163 [57.1%]), the anterior globus pallidus internus (41 of 163 [25.2%]), the posterior globus pallidus internus (25 of 163 [15.3%]), and the anterior limb of the internal capsule (4 of 163 [2.5%]). MAINOUTCOMES AND MEASURES Scores on the Yale Global Tic Severity Scale and adverse events. RESULTS The International Deep Brain Stimulation Database and Registry enrolled 185 patients (of 171 with available data, 37 females and 134 males; mean [SD] age at surgery, 29.1 [10.8] years [range, 13-58 years]). Symptoms of obsessive-compulsive disorder were present in 97 of 151 patients (64.2%) and 32 of 148 (21.6%) had a history of self-injurious behavior. The mean (SD) total Yale Global Tic Severity Scale score improved from 75.01 (18.36) at baseline to 41.19 (20.00) at 1 year after DBS implantation (P

Background:Environmental reduplication which is characterized by reduplication of places has been reported in right hemispheric lesions, particularly but not only in the right frontal region. However, spatial delirium may follow right sub-cortical lesions.Methods:We describe a 53 years-old man who had a reduplicative paramnesia for event alone after an intracerebral haematoma of the right caudate nucleus.Results:MRI Scan showed also an extension of the right caudate nucleus haemorrhage into the ventricular system. Regional cerebral blood flow studied with 99Tcm-HMPAO showed a decrease of perfusion in the right dorso-lateral frontal cortex. To our knowledge, we reported the first case of reduplicative paramnesia of event associated with a right caudate nucleus injury. Similar right frontal deactivation was observed in two cases of reduplicative paramnesia for place, one of them after an infarction of the retro-lenticular portion of the right internal capsulae, the other after a right thalamo-capsular haemorrhage.Conclusion:We suggest that reduplicative paramnesia for event, like the previous cases reported of reduplicative paramnesia for place, may be linked to a subcortical lesion of the frontal lobe inducing a right functional frontal deactivation.

Approximately 1.5% of dementia is due to curable aetiology. We report an isolated dementia syndrome due to a meningeal relapse of acute promyelocytic leukaemia with favourable outcome after appropriate treatment.A 72-year-old woman, in remission of an acute promyelocytic leukaemia, presented a loss of autonomy for several months due to corticosubcortical dementia. Lumbar puncture showed blast cells indicating meningeal relapse of leukaemia. Intrathecal chemotherapy and arsenic trioxide obtained biological and molecular remission as well as restoration of normal cognitive functions.In patients with hematologic past history such as acute promyelocytic leukaemia, an isolated cognitive impairment should alert physicians to search for an isolated neuromeningeal relapse.

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.

To investigate the potential causes of excessive daytime sleepiness in patients with PD-poor sleep quality, abnormal sleep-wakefulness control, and treatment with dopaminergic agents.The authors performed night-time polysomnography and daytime multiple sleep latency tests in 54 consecutive levodopa-treated patients with PD referred for sleepiness, 27 of whom were also receiving dopaminergic agonists.Sleep latency was 6.3 +/- 0.6 minutes (normal8 minutes), and the Epworth Sleepiness score was 14.3 +/- 4.1 (normal10). A narcolepsy-like phenotype (or = 2 sleep-onset REM periods) was found in 39% of the patients, who were sleepier (4.6 +/- 0.9 minutes) than the other 61% of patients (7.4 +/- 0.7 minutes). Periodic leg movement syndromes were rare (15%, range 16 to 43/h), but obstructive sleep apnea-hypopnea syndromes were frequent (20% of patients had an apnea-hypopnea index15/h; range 15.1 to 50.0). Severity of sleepiness was weakly correlated with Epworth Sleepiness score (r = -0.34) and daily dose of levodopa (r = 0.30) but not with dopamine-agonist treatment, age, disease duration, parkinsonian motor disability, total sleep time, periodic leg movement, apnea-hypopnea, or arousal indices.In patients with PD preselected for sleepiness, severity of sleepiness was not dependent on nocturnal sleep abnormalities, motor and cognitive impairment, or antiparkinsonian treatment. The results suggest that sleepiness-sudden onset of sleep-does not result from pharmacotherapy but is related to the pathology of PD.

"Orbitofrontal" and "cingulate" striatofrontal loops and the mesolimbic dopaminergic system that modulates their function have been implicated in motivation and sensitivity to reinforcement in animals. Parkinson's disease (PD) provides a model to assess their implications in humans. The aims of the study were to investigate motivation and sensitivity to reinforcement in non-demented and -depressed PD patients and to evaluate the influence of dopaminergic therapy by comparing patients in "on" (with L-Dopa) and "off" (without L-Dopa) states. Twenty-three PD patients were compared, in both the "on" and "off" states, to 28 controls, using: (1) an Apathy Scale; (2) Stimulus-Reward Learning, Reversal, and Extinction tasks; and (3) a Gambling task. PD patients were found: (1) mildly apathetic; (2) impaired on Stimulus-Reward Learning and Reversal, but not on Extinction; and (3) able to progress in the Gambling task during the first, but not the second assessment. There was no significant correlation between these various deficits. L-Dopa treatment clearly improved motivation, but had more limited and contrasting effects on other variables, decreasing the number of omission errors in Reversal, but increasing the number of perseveration errors in Extinction. These results suggest: (1) an implication of striatofrontal loops in human motivation and explicit and implicit sensitivity to reinforcement; (2) a positive influence of L-Dopa treatment on the subjective evaluation of motivation, but contrasting effects on reward sensitivity.

Disynaptic Ia reciprocal inhibition acts, at the spinal level, by actively inhibiting antagonist motor neurons and reducing the inhibition of agonist motor neurons. The deactivation of this pathway in Parkinson's disease is still debated. Disynaptic reciprocal inhibition of H reflexes in the forearm flexor muscles was examined in 15 control subjects and 16 treated parkinsonian patients at rest and at the onset of a voluntary wrist flexion. Two patients were reassessed 18 h after withdrawal of antiparkinsonian medication. At rest, the level of Ia reciprocal inhibition between the wrist antagonist muscles was not significantly different between patients and controls. In contrast, clear abnormalities of this inhibition were revealed by voluntary movements in the patients. In normal subjects, at the onset of a wrist flexion, Ia reciprocal inhibition showed a large decrease, and we argue that this decrease is supraspinal in origin. On the less affected sides of the patients the descending modulation was still present but lower than in controls; on the more affected sides this modulation had vanished almost completely. These movement-induced abnormalities of disynaptic Ia reciprocal inhibition were closely associated with Parkinson's disease but were probably not dependent on L-dopa. They could play a role in the disturbances of precise voluntary movements observed in Parkinson's disease.

Environmental reduplication which is characterized by reduplication of places has been reported in right hemispheric lesions, particularly but not only in the right frontal region. However, spatial delirium may follow right sub-cortical lesions.We describe a 53 years-old man who had a reduplicative paramnesia for event alone after an intracerebral haematoma of the right caudate nucleus.MRI Scan showed also an extension of the right caudate nucleus haemorrhage into the ventricular system. Regional cerebral blood flow studied with 99Tcm-HMPAO showed a decrease of perfusion in the right dorso-lateral frontal cortex. To our knowledge, we reported the first case of reduplicative paramnesia of event associated with a right caudate nucleus injury. Similar right frontal deactivation was observed in two cases of reduplicative paramnesia for place, one of them after an infarction of the retro-lenticular portion of the right internal capsulae, the other after a right thalamo-capsular haemorrhage.We suggest that reduplicative paramnesia for event, like the previous cases reported of reduplicative paramnesia for place, may be linked to a subcortical lesion of the frontal lobe inducing a right functional frontal deactivation.

International audience; 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.

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.

International audience; 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.

Objective: To assess the effects of bilateral pallidal deep brain stimulation (DBS) on mood and cognitive performance in patients with dystonia before surgery (at baseline, while patients received their usual treatment) and 12 months postoperatively (while patients received neurostimulation and their medications) in a multicenter prospective study. Methods: Twenty-two patients with primary generalized dystonia were evaluated with tests focused on executive functions. The authors considered the patients9 severe disability and selected the following tests: Raven Progressive Matrices 38, Similarities and Arithmetic subtests of the Wechsler Adult Intelligence Scale-R, Grober and Buschke, Wisconsin Card Sorting Test (WCST), verbal fluency, Trail Making Test, and the Beck Depression Inventory. Median age at surgery was 30 years (range = 14 to 54 years), median duration of disease was 18.5 years (range = 4 to 37 years). Results: Before surgery, no patients showed cognitive decline or depression. The surgical procedure appeared to be benign cognitively. One year after surgery, free recall improved. There was a significant reduction in the number of errors in the WCST. No behavioral or mood changes were found. Conclusions: Bilateral pallidal stimulation has a good benefit-to-risk ratio as it did not negatively affect cognitive performance and mood in primary dystonia, while a significant motor improvement was obtained. Moreover, a significant mild improvement in executive functions was observed, which may have been related either to the surgical treatment or to the marked decrease in anticholinergic drugs.

High frequency stimulation of the subthalamic nucleus (STN) is an alternative but expensive neurosurgical treatment for parkinsonian patients with levodopa induced motor complications.To assess the safety, clinical effects, quality of life, and economic cost of STN stimulation.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.The Unified Parkinson's Disease Rating Scale (UPDRS) motor score improved by 57% (p0.0001) and activities of daily living improved by 48% (p0.0001) at 12 month follow up. Double blind motor scoring improved by 51% at 3 month follow up (p0.0001). The total PD Quality of Life Questionnaire (PDQL-37) score improved by 28% (p0.001). 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 (p0.0001) 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.STN stimulation has good outcomes with relatively low risk and little cost burden in PD patients with levodopa induced motor complications.

Background: Myoclonus dystonia syndrome (MDS) is an autosomal dominant movement disorder caused by mutations in the epsilon-sarcoglycan gene ( SGCE ) on chromosome 7q21. Methods: We have screened for SGCE mutations in index cases from 76 French patients with myoclonic syndromes, including myoclonus dystonia (M-D), essential myoclonus (E-M), primary myoclonic dystonia, generalised dystonia, dystonia with tremor, and benign hereditary chorea. All coding exons of the SGCE gene were analysed. The DYT1 mutation was also tested. Results: Sixteen index cases had SGCE mutations while one case with primary myoclonic dystonia carried the DYT1 mutation. Thirteen different mutations were found: three nonsense mutations, three missense mutations, three splice site mutations, three deletions, and one insertion. Eleven of the SGCE index cases had M-D and five E-M. No SGCE mutations were detected in patients with other phenotypes. The total number of mutation carriers in the families was 38, six of whom were asymptomatic. Penetrance was complete in paternal transmissions and null in maternal transmissions. MDS patients with SGCE mutation had a significantly earlier onset than the non-carriers. None of the patients had severe psychiatric disorders. Conclusion: This large cohort of index patients shows that SGCE mutations are primarily found in patients with M-D and to a lesser extent E-M, but are present in only 30% of these patients combined (M-D and E-M).

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

Deep brain stimulation (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.

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

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.

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.

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.

High-frequency stimulation of the subthalamic nucleus (STN) constitutes one of the most effective treatments for advanced forms of Parkinson's disease. The cost and potential risks of this procedure encourage the determination of clinical characteristics of patients that will have the best postoperative outcome. Forty-one Parkinson's disease patients underwent surgery for bilateral STN stimulation. The selection criteria were severe parkinsonian motor disability, clear response of symptoms to levodopa, occurrence of disabling levodopa-related motor complications and the absence of dementia and significant abnormalities on brain MRI. Clinical evaluation was performed 1 month before and 6 months after surgery. The improvement in the activities of daily living subscale of the Unified Parkinson's Disease Rating Scale, Part II (UPDRS II) and parkinsonian motor disability (UPDRS III) was greater when the preoperative scores for activities of daily living and parkinsonian motor disability, in particular axial symptoms, such as gait disorders and postural instability assessed at the time of maximal clinical improvement (on drug), were lower. Age and disease duration were not predictive, but parkinsonian motor disability tended to be more improved in patients with younger age and shorter disease duration. The severity of levodopa-related motor complications was not a predictive factor. The outcome of STN stimulation was excellent in levodopa-responsive forms of Parkinson's disease, i.e. in patients with selective brain dopaminergic lesions, and moderate in patients with axial motor symptoms and cognitive impairment known to be less responsive or unresponsive to levodopa treatment, i.e. when brain non-dopaminergic lesions develop in addition to the degeneration of the nigrostriatal dopaminergic system. The results are consistent with the classical inclusion criteria for STN stimulation, but imply that the decision to operate on the oldest patients and/or patients with gait and postural disorders, who are poorly responsive to levodopa, should be weighed carefully.

Levodopa-induced dyskinesias (LIDs) in patients with Parkinson's disease are considered to result from the severity of dopaminergic denervation in the striatum, which is an irrevocable phenomenon, and sensitization induced by long-term intermittent administration of levodopa. Taking advantage of the 64% reduction of levodopa treatment allowed in 12 Parkinson's disease patients by continuous high-frequency stimulation of the subthalamic nucleus, we evaluated the severity of parkinsonian motor disability and LIDs during two levodopa challenges performed before the surgical implantation of the stimulation electrodes and after 8.8 months of continuous bilateral subthalamic nucleus stimulation that was interrupted 2 hours before the levodopa test. Motor disability during the "off" and "on" drug periods was unchanged. The severity of LIDs during the "on" period and dystonia during the "off" period decreased by 54% and 62%, respectively. The reduced severity of LIDs in the absence of subthalamic nucleus stimulation demonstrates that the sensitization phenomenon resulting from long-term intermittent levodopa administration is partially reversible.