Oral and intestinal dysbiosis in Parkinson's disease.

The suspicion of an origin of Parkinson's disease (PD) at the periphery of the body and the involvement of environmental risk factors in the pathogenesis of PD have directed the attention of the scientific community towards the microbiota. The microbiota represents all the microorganisms residing both in and on a host. It plays an essential role in the physiological functioning of the host. In this article, we review the dysbiosis repeatedly demonstrated in PD and how it influences PD symptoms. Dysbiosis is associated with both motor and non-motor PD symptoms. In animal models, dysbiosis only promotes symptoms in individuals genetically susceptible to Parkinson's disease, suggesting that dysbiosis is a risk factor but not a cause of Parkinson's disease. We also review how dysbiosis contributes to the pathophysiology of PD. Dysbiosis induces numerous and complex metabolic changes, resulting in increased intestinal permeability, local and systemic inflammation, production of bacterial amyloid proteins that promote α-synuclein aggregation, as well as a decrease in short-chain fatty acid-producing bacteria that have anti-inflammatory and neuroprotective potential. In addition, we review how dysbiosis decreases the efficacy of dopaminergic treatments. We then discuss the interest of dysbiosis analysis as a biomarker of Parkinson's disease. Finally, we give an overview of how interventions modulating the gut microbiota such as dietary interventions, pro-biotics, intestinal decontamination and fecal microbiota transplantation could influence the course of PD.

Differentiation between Parkinson disease and other forms of Parkinsonism using support vector machine analysis of susceptibility-weighted imaging (SWI): initial results.

OBJECTIVES: To diagnose Parkinson disease (PD) at the individual level using pattern recognition of brain susceptibility-weighted imaging (SWI). METHODS: We analysed brain SWI in 36 consecutive patients with Parkinsonism suggestive of PD who had (1) SWI at 3 T, (2) brain (123)I-ioflupane SPECT and (3) extensive neurological testing including follow-up (16 PD, 67.4 ± 6.2 years, 11 female; 20 OTHER, a heterogeneous group of atypical Parkinsonism syndromes 65.2 ± 12.5 years, 6 female). Analysis included group-level comparison of SWI values and individual-level support vector machine (SVM) analysis. RESULTS: At the group level, simple visual analysis yielded no differences between groups. However, the group-level analyses demonstrated increased SWI in the bilateral thalamus and left substantia nigra in PD patients versus other Parkinsonism. The inverse comparison yielded no supra-threshold clusters. At the individual level, SVM correctly classified PD patients with an accuracy above 86 %. CONCLUSIONS: SVM pattern recognition of SWI data provides accurate discrimination of PD among patients with various forms of Parkinsonism at an individual level, despite the absence of visually detectable alterations. This pilot study warrants further confirmation in a larger cohort of PD patients and with different MR machines and MR parameters.

Individual detection of patients with Parkinson disease using support vector machine analysis of diffusion tensor imaging data: initial results.

BACKGROUND AND PURPOSE: Brain MR imaging is routinely performed in the work-up of suspected PD, yet its role is essentially limited to the exclusion of other pathologies. We performed a pattern-recognition analysis based on DTI data to detect subjects with PD at the individual level. MATERIALS AND METHODS: We included 40 consecutive patients with Parkinsonism suggestive of PD who had DTI at 3T, brain (123)I ioflupane SPECT (DaTSCAN), and extensive neurologic testing including follow-up (17 PD: age range, 67.8 ± 6.7 years; 9 women; 23 Other: consisting of atypical forms of Parkinsonism; age range, 67.2 ± 9.7 years; 7 women). Data analysis included group-level TBSS and individual-level SVM classification. RESULTS: At the group level, patients with PD versus Other had spatially consistent increase in FA and decrease in RD and MD in a bilateral network, predominantly in the right frontal white matter. At the individual level, SVM correctly classified patients with PD at the individual level with accuracies up to 97%. CONCLUSIONS: Support vector machine-based pattern recognition of DTI data provides highly accurate detection of patients with PD among those with suspected PD at an individual level, which is potentially clinically applicable. Because most suspected subjects with PD undergo brain MR imaging, already existing MR imaging data may be reused; this practice is very cost-efficient.

Naloxone-responsive acute dystonia and parkinsonism following general anaesthesia.

Various movement disorders such as dystonia may acutely develop during or at emergence from general anaesthesia in patients with or without pre-existing Parkinson disease. These movements are triggered by a variety of drugs including propofol, sevoflurane, anti-emetics, antipsychotics and opioids. The postulated mechanism involves an imbalance between dopaminergic and cholinergic neurotransmitters in the basal ganglia. We report an acute, severe and generalised dystonic reaction in an otherwise healthy woman at emergence from general anaesthesia, dramatically reversed by the administration of naloxone, pointing to a potential role of the fentanyl and morphine that the patient had received. Recent literature on the mechanisms of abnormal movements induced by opioids are discussed. The severity of the reaction with usual doses of opioids, in a patient with no prior history of parkinsonism, led to further investigation that demonstrated the possibility of an enhanced susceptibility to opioids, involving a genetically determined abnormal function of glycoproteine-P and catechol-O-methyltransferase.

[Autoantibodies in neurological diseases: clinical implications]. / Autoanticorps en neurologie: implications cliniques.

Autoantibodies are defined as antibodies directed against self antigens, i.e., against a normal antigenic endogenous tissue constituent. They can be the immediate cause of the neurological syndrome or be detected as an epiphenomenon of the pathogenic process. Autoantibodies are often considered useful biomarkers for the improvement of diagnostic accuracy, for the staging of disease progression or for the follow up of a biological response to a therapeutic intervention. The purpose of this article is to review the autoantibodies that are available to investigate immune-mediated neurological conditions. The detection of some of these autoantibodies may help the clinician to establish a definite diagnosis which may further facilitate the therapeutic decision.

Restless legs syndrome: an early manifestation of Huntington's disease?

BACKGROUND: Far from being uniform, Huntington's disease (HD)'s phenotype encompasses a large variety of motor and non-motor symptoms which occur in various combinations in individual patients. AIM: To describe an unusual association between restless legs syndrome (RLS) and HD. METHODS AND RESULTS: We report a patient with an atypical presentation of genetically demonstrated HD, who developed typical RLS a few years prior to and during the course of HD. Common causes of RLS were excluded and the polysomnography confirmed frequent and severe periodic limb movements during sleep and while awake. CONCLUSIONS: We propose RLS as an uncommon but early feature of HD in some patients, and suggest adding HD to the already long list of RLS secondary to neurodegenerative conditions.

[Impulse control disorders and Parkinson's disease]. / Troubles du contrôte des impulsions et maladie de Parkinson.

A variety of behavioral disorders occurring abruptly in patients with Parkinson's disease (PD) has been recently published and attracted considerable attention in the press. Taking the form of pathological gambling, compulsive shopping, addiction to Internet and to other recreational activities, hypersexuality or bulimia, impulse control disorders (ICD) related to PD are probably more frequent than previously appreciated and may have consequences as spectacular as disastrous for the involved patients. ICD are currently viewed as particular adverse reactions to antiparkinsonian medications, notably to dopamine agonists, and, accordingly, tend to improve or disappear when PD therapy is appropriately adjusted.

[Hysteria: an historical entity, a psychiatric condition or a neurological disease?]. / L'hystérie: une entité historique, un trouble psychiatrique ou une maladie neurologique?

It has been suggested that hysteria had waned and was an old-fashioned, stigmatizing and false concept, reflecting the incapacity of the medical community to establish a diagnosis in certain situations. Nowadays, however, those disturbances, now referred to as conversion or dissociative disorders, still remain a frequent and incapacitating condition that every clinician faces. These past decades, several studies have tried to better describe their clinical presentation and their neurobiological mechanisms, with the help of the development of new neuroimaging techniques. If the neurobiological correlates are now better understood, efficient treatments are still lacking and only a multidisciplinary (general practitioners, neurologists and psychiatrists) and individually-tailored therapy might be beneficial to the patients.

Sub-acute delayed failure of subthalamic DBS in Parkinson's disease: the role of micro-lesion effect.

OBJECTIVE: To study delayed failure after subthalamic nucleus (STN) deep brain stimulation in Parkinson's disease (PD) patients. METHODS: Out of 56 consecutive bilaterally STN-implanted PD patients, we selected subjects who, after initial clinical improvement (1 month after surgery), lost benefit (delayed failure, DF). RESULTS: Five patients developed sub-acutely severe gait disorders (DF). In 4/5 DF patients, a micro-lesion effect, defined as improvement without stimulation, was observed; immediate post-operative MRI demonstrated electrode located above or behind to the STN. CONCLUSIONS: Patients presenting micro-lesion effect should be carefully monitored, as this phenomenon can mask electrodes misplacement and evolution in DF.

Study of a Swiss dopa-responsive dystonia family with a deletion in GCH1: redefining DYT14 as DYT5.

OBJECTIVE: To report the study of a multigenerational Swiss family with dopa-responsive dystonia (DRD). METHODS: Clinical investigation was made of available family members, including historical and chart reviews. Subject examinations were video recorded. Genetic analysis included a genome-wide linkage study with microsatellite markers (STR), GTP cyclohydrolase I (GCH1) gene sequencing, and dosage analysis. RESULTS: We evaluated 32 individuals, of whom 6 were clinically diagnosed with DRD, with childhood-onset progressive foot dystonia, later generalizing, followed by parkinsonism in the two older patients. The response to levodopa was very good. Two additional patients had late onset dopa-responsive parkinsonism. Three other subjects had DRD symptoms on historical grounds. We found suggestive linkage to the previously reported DYT14 locus, which excluded GCH1. However, further study with more stringent criteria for disease status attribution showed linkage to a larger region, which included GCH1. No mutation was found in GCH1 by gene sequencing but dosage methods identified a novel heterozygous deletion of exons 3 to 6 of GCH1. The mutation was found in seven subjects. One of the patients with dystonia represented a phenocopy. CONCLUSIONS: This study rules out the previously reported DYT14 locus as a cause of disease, as a novel multiexonic deletion was identified in GCH1. This work highlights the necessity of an accurate clinical diagnosis in linkage studies as well as the need for appropriate allele frequencies, penetrance, and phenocopy estimates. Comprehensive sequencing and dosage analysis of known genes is recommended prior to genome-wide linkage analysis.

Long-term outcome of 50 consecutive Parkinson's disease patients treated with subthalamic deep brain stimulation.

OBJECTIVE: To describe the long-term outcome in 50 consecutive advanced Parkinson's disease (PD) patients treated with subthalamic nucleus deep brain stimulation (STN-DBS). METHOD: Assessments were carried out at baseline, 6 months, 2 years, and 5 years postoperatively. RESULTS: Compared to baseline scores without medication, we found a highly significant improvement of UPDRS III with stimulation, maintained at 5 years (p<0.001). This improvement, however, tended to diminish over time. Dyskinesia and off periods were also improved (p<0.0001 for both). Seventeen patients died during follow-up, who tended to be older at surgery (p<0.01). CONCLUSIONS: STN-DBS is an effective treatment for advanced PD patients, and the beneficial effect is maintained at 5 years. However, worsening occurs over time due to disease progression.

Levodopa-induced ocular dyskinesia in Parkinson's disease.

Levodopa (LD)-induced dyskinesia (LID), one of the most common motor complications in advanced Parkinson's disease (PD), involve mostly the limbs, trunk and head, but unusual locations have been reported including respiratory muscles, the face and the eyes. The aim of this study was to further investigate the frequency and characteristics of LD-related abnormal involuntary eye movements (AIEMs) in PD. Thirty-two patients with advanced PD and various motor complications were evaluated and videotaped in an ON and OFF state. We found AIEMs in five patients (16%) which were present exclusively during the ON state and which completely disappeared when OFF. They consisted of repeated, stereotyped upward and/or sideways gaze deviation movements, sometimes phasic, brief and jerky, sometimes tonic and sustained for several seconds. The main direction of gaze deviation was toward the side more affected by parkinsonism. AIEMs typically paralleled limb and trunk LID and were modulated by the same facilitation and inhibitory maneuvers. We concluded that AIEMs are not uncommon in advanced PD and represent a particular topography of LID, hence the term 'ocular dyskinesia' to designate these AIEMs that seem to have a specific pattern in PD as compared with other forms of parkinsonism.