French guidelines for the diagnosis and management of Tourette syndrome.

The term "Gilles de la Tourette syndrome", or the more commonly used term "Tourette syndrome" (TS) refers to the association of motor and phonic tics which evolve in a context of variable but frequent psychiatric comorbidity. The syndrome is characterized by the association of several motor tics and at least one phonic tic that have no identifiable cause, are present for at least one year and appear before the age of 18. The presence of coprolalia is not necessary to establish or rule out the diagnosis, as it is present in only 10% of cases. The diagnosis of TS is purely clinical and is based on the symptoms defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). No additional tests are required to confirm the diagnosis of TS. However, to exclude certain differential diagnoses, further tests may be necessary. Very frequently, one or more psychiatric comorbidities are also present, including attention deficit hyperactivity disorder, obsessive-compulsive disorder, anxiety, explosive outbursts, self-injurious behaviors, learning disorders or autism spectrum disorder. The condition begins in childhood around 6 or 7 years of age and progresses gradually, with periods of relative waxing and waning of tics. The majority of patients experience improvement by the end of the second decade of life, but symptoms may persist into adulthood in around one-third of patients. The cause of TS is unknown, but genetic susceptibility and certain environmental factors appear to play a role. The treatment of TS and severe forms of tics is often challenging and requires a multidisciplinary approach (involving the general practitioner (GP), pediatrician, psychiatrist, neurologist, school or occupational physicians, psychologist and social workers). In mild forms, education (of young patients, parents and siblings) and psychological management are usually recommended. Medical treatments, including antipsychotics, are essential in the moderate to severe forms of the disease (i.e. when there is a functional and/or psychosocial discomfort linked to tics). Over the past decade, cognitive-behavioral therapies have been validated for the treatment of tics. For certain isolated tics, botulinum toxin injections may also be useful. Psychiatric comorbidities, when present, often require a specific treatment. For very severe forms of TS, treatment by deep brain stimulation offers real therapeutic hope. If tics are suspected and social or functional impairment is significant, specialist advice should be sought, in accordance with the patient's age (psychiatrist/child psychiatrist; neurologist/pediatric neurologist). They will determine tic severity and the presence or absence of comorbidities. The GP will take over the management and prescription of treatment: encouraging treatment compliance, assessing side effects, and combating stigmatization among family and friends. They will also play an important role in rehabilitation therapies, as well as in ensuring that accommodations are made in the patient's schooling or professional environment.

Postural instability and gait disorders after subthalamic nucleus deep brain stimulation in Parkinson's disease: a PET study.

INTRODUCTION: Patients with Parkinson's disease sometimes report postural instability and gait disorders (PIGD) after subthalamic nucleus deep brain stimulation (STN-DBS). Whether this is the direct consequence of DBS or the result of natural disease progression is still subject to debate. OBJECTIVE: To compare changes in brain metabolism during STN-DBS between patients with and without PIGD after surgery. METHODS: We extracted consecutive patients from a database where all Rennes Hospital patients undergoing STN-DBS are registered, with regular prospective updates of their clinical data. Patients were divided into two groups (PIGD and No PIGD) according to changes after surgery, as measured with a composite score based on the selected Unified Parkinson's Disease Rating Scale items. All patients underwent positron emission tomography with 18[F]-fluorodeoxyglucose 3 months before and after surgery. We ran an ANOVA with two factors (group: PIGD vs. No PIGD; and phase: preoperative vs. postoperative) on SPM8 to compare changes in brain metabolism between the two groups. RESULTS: Participants were 56 patients, including 10 in the PIGD group. The two groups had similar baseline (i.e., before surgery) characteristics. We found two clusters of increased metabolism in the PIGD group relative to the No PIGD group: dorsal midbrain/pons, including locomotor mesencephalic region and reticular pontine formation, and right motor cerebellum. CONCLUSION: We found different metabolic changes during DBS-STN among patients with PIGD, concerning brain regions that are already known to be involved in gait disorders in Parkinson's disease, suggesting that DBS is responsible for the appearance of PIGD.

Subthalamic deep brain stimulation influences complex emotional musical experience in Parkinson's disease.

Subthalamic deep brain stimulation (STN DBS) is an effective treatment for reducing the motor symptoms of patients with Parkinson's disease (PD), but several side effects have been reported, concerning the processing of emotions. Music has been shown to evoke powerful emotional experiences - not only basic emotions, but also complex, so-called aesthetic experiences. The goal of the present study was therefore to investigate how STN DBS influences the experience of both basic and more complex musical emotions in patients with PD. In a three-group between-participants design, we compared healthy controls (HC), patients receiving STN DBS (PD-DBS), and patients who were candidates for STN DBS and receiving medication only (PD-MO) on their assessments of subjectively experienced musical emotions. Results showed that in general, the experience of musical emotions differed only marginally between the PD-MO, PD-DBS, and HC groups. Nonetheless, we were able to discern subtle but distinct effects of PD and STN DBS in the emotional responses. Happy music, for instance, seemed to induce a heightened experience of negative emotions (tension) in PD-MO patients. STN DBS appeared to normalize this particular effect, but increased nostalgic feelings - a rather complex affective experience - in response to the same emotional stimuli. This should not be taken as indicating a bias for nostalgia in the PD-DBS subgroup, as these patients found music inducing melancholy to be less nostalgic and more joyful than HC did. In conclusion, our study showed that music elicits slightly altered emotional experiences in patients with and without STN DBS. In particular, STN DBS seems to induce less distinct emotional responses, blurring the boundaries between complex musical emotions.

Parkinson's disease associated with 22q11.2 deletion: Clinical characteristics and response to treatment.

BACKGROUND: While it is known that 22q11.2 microdeletions (22q11.2-del) increase the risk of Parkinson's disease (PD), the characteristics of PD associated with 22q11.2-del have not been specifically explored. OBJECTIVE: This report aimed to assess the clinical characteristics and treatment responses of PD patients with 22q11.2-del, and to describe any features that might lead neurologists to investigate the comorbidity. METHODS: Nine PD patients (eight men, one woman) with 22q11.2-del were followed at seven centers of the French PD Expert Network (Ns-Park). RESULTS: PD diagnosis was made before 22q11.2-del diagnosis in seven cases; their main characteristics were early onset (32-48 years) and good initial levodopa sensitivity, but with a course characterized by severe and early-onset levodopa-induced motor complications and psychiatric manifestations. Three patients received deep brain stimulation (DBS) that was effective. CONCLUSION: Searching for 22q11.2-del in PD patients presenting with suggestive features is relevant as the clinical presentation is similar to idiopathic PD, but with other associated characteristics, including a severe evolution. Results with DBS are similar to those reported for idiopathic PD.

[Psychogenic movement disorders]. / Les mouvements anormaux psychogènes.

Psychogenic Movement Disorders (PMDs) are a subtype of conversion disorder, classified under somatoform disorders in the DSM. Diagnosis and treatment of PMDs are challenging for both neurologists and psychiatrists. Typical clinical characteristics of these disorders are acute onset, fast progression, movement patterns incongruent with organic movement disorders, distractibility, variability and simultaneous occurrence of various abnormal movements and dysfunctions. The diagnosis of PMDs should not be regarded as a diagnosis of exclusion and electrophysiology is not always helpful. The cause of PMDs is unknown and the underlying brain mechanisms remain uncertain. However, recent functional magnetic resonance imaging studies have demonstrated altered blood flow in conversion disorders that may reflect changes in synaptic activity. Involvement of allied health professionals and psychotherapy continue to be the mainstay of treatment.

Subthalamic nucleus stimulation in Parkinson disease induces apathy: a PET study.

OBJECTIVE: Apathy may be induced by subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson disease (PD). We therefore wished to test the hypothesis that apathy induced by STN-DBS correlates with changes in glucose metabolism, using (18)FDG-PET. METHODS: Twelve patients with PD were assessed 3 months before (M-3) and 3 months after (M+3) STN-DBS with (18)FDG-PET and the Apathy Evaluation Scale. RESULTS: Apathy had significantly worsened at M+3 after STN-DBS. Positive correlations were observed between this variation in apathy scores and changes in glucose metabolism, especially in the right frontal middle gyrus (Brodmann area [BA] 10) and right inferior frontal gyrus (BA 46 and BA 47). Negative correlations between the two were observed in the right posterior cingulate gyrus (BA 31) and left medial frontal lobe (BA 9). CONCLUSION: These preliminary results confirm the role of the subthalamic nucleus in associative and limbic circuitry in humans and suggest that it is a key basal ganglia structure in motivation circuitry.

Emotion recognition impairment and apathy after subthalamic nucleus stimulation in Parkinson's disease have separate neural substrates.

OBJECTIVE: To test the hypothesis that emotion recognition and apathy share the same functional circuit involving the subthalamic nucleus (STN). METHODS: A consecutive series of 17 patients with advanced Parkinson's disease (PD) was assessed 3 months before (M-3) and 3 months (M+3) after STN deep brain stimulation (DBS). Mean (+/-S.D.) age at surgery was 56.9 (8.7) years. Mean disease duration at surgery was 11.8 (2.6) years. Apathy was measured using the Apathy Evaluation Scale (AES) at both M-3 and M3. Patients were also assessed using a computerised paradigm of facial emotion recognition [Ekman, P., & Friesen, W. V. (1976). Pictures of facial affect. Palo Alto: Consulting Psychologist Press] before and after STN DBS. Prior to this, the Benton Facial Recognition Test was used to check that the ability to perceive faces was intact. RESULTS: Apathy had significantly worsened at M3 (42.5+/-8.9, p=0.006) after STN-DBS, in relation to the preoperative assessment (37.2+/-5.5). There was also a significant reduction in recognition percentages for facial expressions of fear (43.1%+/-22.9 vs. 61.6%+/-21.4, p=0.022) and sadness (52.7%+/-19.1 vs. 67.6%+/-22.8, p=0.031) after STN DBS. However, the postoperative worsening of apathy and emotion recognition impairment were not correlated. CONCLUSIONS: Our results confirm that the STN is involved in both the apathy and emotion recognition networks. However, the absence of any correlation between apathy and emotion recognition impairment suggests that the worsening of apathy following surgery could not be explained by a lack of facial emotion recognition and that its behavioural and cognitive components should therefore also be taken into consideration.

Subthalamic nucleus stimulation affects orbitofrontal cortex in facial emotion recognition: a PET study.

Deep brain stimulation (DBS) of the bilateral subthalamic nucleus (STN) in Parkinson's disease is thought to produce adverse events such as emotional disorders, and in a recent study, we found fear recognition to be impaired as a result. These changes have been attributed to disturbance of the STN's limbic territory and would appear to confirm that the negative emotion recognition network passes through the STN. In addition, it is now widely acknowledged that damage to the orbitofrontal cortex (OFC), especially the right side, can result in impaired recognition of facial emotions (RFE). In this context, we hypothesized that this reduced recognition of fear is correlated with modifications in the cerebral glucose metabolism of the right OFC. The objective of the present study was first, to reinforce our previous results by demonstrating reduced fear recognition in our Parkinson's disease patient group following STN DBS and, second, to correlate these emotional performances with glucose metabolism using (18)FDG-PET. The (18)FDG-PET and RFE tasks were both performed by a cohort of 13 Parkinson's disease patients 3 months before and 3 months after surgery for STN DBS. As predicted, we observed a significant reduction in fear recognition following surgery and obtained a positive correlation between these neuropsychological results and changes in glucose metabolism, especially in the right OFC. These results confirm the role of the STN as a key basal ganglia structure in limbic circuits.

[Continuous subcutaneous infusion of apomorphine for the treatment of Parkinson's disease]. / L'apomorphine en perfusion sous-cutanée continue dans le traitement de la maladie de Parkinson.

Apomorphine administered by subcutaneous infusion has been used efficiently in parkinsonian patients to treat severe motor fluctuations and levodopa-induced dyskinesias. Despite increasing evidence of its efficacy and its relative safety, apomorphine infusion therapy is still underused. This article reviews pharmacokinetic properties, efficacy, tolerability and indications of apomorphine infusion in Parkinson's disease.

Does subthalamic nucleus stimulation induce apathy in Parkinson's disease?

BACKGROUND: Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) has been shown to significantly improve motor symptoms in advanced Parkinson's disease (PD). Only few studies, however, have focused on the non-motor effects of DBS. METHODS: A consecutive series of 15 patients was assessed three months before (M-3), then three months (M3) and six months (M6) after surgery. Mean (+/- SD) age at surgery was 59.7 (7.6). Mean disease duration at surgery was 12.2 (2.8) years. The Mini International Neuropsychiatric Inventory was used to assess psychiatric disorders three months before surgery. Depression was evaluated using Montgomery and Asberg Rating Scale (MADRS). Anxiety was evaluated using the AMDP system (Association for Methodology and Documentation in Psychiatry). Apathy was particularly evaluated using the Apathy Evaluation Scale (AES) and the Starkstein Scale. All these scales were performed at every evaluation. RESULTS: Apathy worsened at M3 and M6 after STN-DBS in comparison with the preoperative evaluation: the AES mean score was significantly impaired between the preoperative (38.4+/-7.1) and both the postoperative M3 (44.6+/-9.5, p = 0.003) and M6 scores (46.0+/-10.9, p = 0.013). Significant worsening of apathy was confirmed using the Starkstein scale. There was no evidence of depression: the mean MADRS score did not differ before surgery (9.1+/-7.4) and at both M3 (8.6+/-8.2) and M6 (9.9+/-7.7) after STN-DBS. The anxiety level did not change between preoperative (9.4+/-9.2) and both M3 (5.5+/-4.5) and M6 (6.6+/-4.6) postoperative states. CONCLUSION: Although STN-DBS constitutes a therapeutic advance for severely disabled patients with Parkinson's disease, we should keep in mind that this surgical procedure may contribute to the inducing of apathy. Our observation raises the issue of the direct influence of STN- DBS on the limbic system by diffusion of stimulus to the medial limbic compartment of STN.

Experimental assessment and analytical 2D predictions of the stocking pressures induced on a model leg by Medical Compressive Stockings.

Stocking supports have represented, for more than two millennia, the most efficient way to treat the veinous diseases and lymphatic disorders. Although this treatment consists solely in the application of a mechanical pressure to help the blood in reaching back the heart, very little is known on this mechanical effort exerted on a human limb by knitted fabrics. However, nowadays the precise assessment of this pressure distribution is crucial in fitting the treatment to the patient pathology and morphology. In order to describe rationally, for the first time, the pressure distribution induced on a leg, a combined experiment-simulation 2D methodology has been set to validate this mechanical approach. The present article is the first part of a two-papers communication. Experimental aspects are presented here, first to measure these stocking pressures on a rigid leg using the SIGaT((R)) device based on a pneumatic sensor. Then, the knitted fabric mechanical response is characterized under uniaxial tension for large strains, to evaluate the simplified Laplace-based pressure that can be compared with the pressure measurements, knowing the local curvature radii of a leg section. This experimental approach is to be completed with numerical simulations of the stocking mechanism on the same model leg.

[Multiple cerebral infarcts associated with livedo secondary to anti-cancer therapy with interleukin 2 and interferon alpha]. / Infarctus cérébraux multiples associés à un livedo secondaires à un traitement anticancéreux par interleukine 2 et interféron alpha.

Anticancer drugs rarely cause strokes. We report the case of a woman treated for a kidney cancer by IL2 and IFN alpha, having developed multiple strokes associated with a livedo. The responsibility of IL2 and IFN alpha seemed likely. The association with a transitory livedo suggested that the pathological process might be a cerebral angiopathy with arterial vasospasms.