Hand Dystonia after Focused Ultrasound Thalamotomy in Essential Tremor.

INTRODUCTION: Magnetic resonance guided focused ultrasound (MRgFUS) thalamotomy is an effective treatment for drug-resistant tremor. The most frequent side effects are ataxia, gait disturbance, paresthesias, dysgeusia, and hemiparesis. Here, we report the first case of thalamic hand dystonia rapidly occurring after MRgFUS thalamotomy of the ventral intermediate nucleus (V.im). CASE PRESENTATION: MRgFUS thalamotomy was performed in a 60-year-old left-handed patient for his disabling medically refractory essential tremor. The intervention resulted in a marked reduction of his action tremor. However, the patient developed an unvoluntary abnormal posture in his left hand a few days after the procedure with difficulty holding a cigarette between his fingers. Brain MRI revealed the expected MRgFUS lesion within the right V.im as well as an extension of the lesion anteriorly to the V.im in the ventro-oralis nucleus. Tractography showed that the lesion disrupted the dentato-rubro-thalamic tract as expected with a lesion suppressing tremor. However, the lesion also was interrupted fibers connecting to the superior frontal and pre-central cortices (primary motor cortex, premotor cortex, and supplementary area). We hypothesized that the interventional MRgFUS thalamotomy was slightly off target, which induced a dysfunction within the cortico-striato-thalamo-cortical network and the cerebello-thalamo-cortical pathway reaching a sufficient threshold of basal ganglia/cerebellum circuitry interference to induce dystonia. CONCLUSION: This rare side effect emphasizes the risk of imbalance within the dystonia network (i.e., basal ganglia-cerebello-thalamo-cortical circuit) secondary to V.im thalamotomy.

Neurology of Aging: Adapting Neurology Provision for an Aging Population.

BACKGROUND: Over the past few decades, advances in the neurology of aging have been considerable and have led to a better understanding of the science of age-related neurological disorders. Likewise, it changed the perception of classical neurology practice, research, and the way of looking at age-related conditions. Neurological disorders are the most frequent cause of major disability in the elderly and account for almost half of the incapacitation occurring beyond age 65 and more than 90% of serious dependency. However, a number of neurological changes occur also in the absence of a specific disease, making the assessment and management of neurological complaints and findings a specific expertise. SUMMARY: Maximizing success in clinical care of the elderly requires expertise in geriatric neurology, which includes an understanding of current research regarding aging and age-related neurological dysfunctions, and the ability to work with other geriatric healthcare providers. Although current therapies for neurodegenerative diseases mainly offer symptomatic relief without slowing progression, the landscape is evolving. Biomarkers of pathology and neuroimaging have continued to develop, with a significant impact on diagnosis and treatment. These advances have not only helped to improve our knowledge of disease pathophysiology but also disease stages, guiding symptomatic monitoring, and possible therapeutic options at a pre-symptomatic stage. KEY MESSAGES: Neurological disorders are a leading cause of major disability and dependency in the elderly, underscoring the need for expertise in geriatric neurology for effective clinical care of this population. Although current therapies for neurodegenerative diseases primarily provide symptomatic relief without slowing disease progression, advancements in biomarkers and neuroimaging are significantly evolving. These advancements enhance our understanding of disease pathophysiology and stages, guiding symptomatic monitoring and potential therapeutic options at a pre-symptomatic stage. As knowledge about age-associated conditions is steadily rising and geriatric medicine gains further recognition, this article argues for a new focus on the role of neurologists in geriatric medicine, emphasizing the importance of integrating current research and collaborative care approaches in the management of elderly patients.

[Psychiatric symptoms of Lewy body dementia]. / Symptômes psychiatriques de la démence à corps de Lewy.

Lewy body dementia (LBD) is the second most common neurodegenerative disorder after Alzheimer's disease. Cognitive fluctuations, visual hallucinations, parkinsonian signs, and rapid eye movement sleep behavior disorder (RBD) are diagnostic criteria. However, the diverse clinical presentations complicate diagnosis and management, as the disease may begin with psychiatric symptoms, confusion, sleep disturbances, and/or autonomic dysfunction. Its progression often leads to neuropsychiatric and behavioral symptoms that can overshadow cognitive impairments. Diagnosing LBD is crucial to avoid first iatrogenic effects (e.g., neuroleptics), and then facilitate a personalized approach to address cognitive and neuropsychiatric management, while considering comorbidities.

La démence à corps de Lewy (DCL) est la deuxième pathologie neurodégénérative la plus fréquente après la maladie d'Alzheimer. Les fluctuations cognitives, hallucinations visuelles, signes parkinsoniens, et le trouble du comportement en sommeil paradoxal (TCSP) font partie des critères diagnostics. Cependant, la diversité des présentations cliniques rend le diagnostic et la prise en charge difficiles, la maladie pouvant débuter avec des manifestations psychiatriques, confusion, troubles du sommeil et/ou dysautonomiques. Sa progression entraîne souvent des troubles neuropsychiatriques et du comportement qui peuvent prédominer sur les troubles cognitifs. Diagnostiquer la DCL permet d'abord d'éviter l'iatrogénie (par ex. neuroleptiques) et de personnaliser la prise en charge cognitive et neuropsychiatrique, en tenant compte des comorbidités.

Successful MRI-Guided Focused Ultrasound Thalamotomy after Ipsilateral Gamma Knife Radiosurgery for Essential Tremor: A Case Report with Video.

We report the case of a 67-year-old left-handed female patient with disabling medically refractory essential tremor who underwent successful right-sided magnetic resonance-guided focused ultrasound (MRgFUS) of the ventral intermediate nucleus after ipsilateral gamma knife radiosurgery (GKRS) thalamotomy performed 3 years earlier. The GKRS had a partial effect on her postural tremor without side effects, but there was no reduction of her kinetic tremor or improvement in her quality of life (QoL). The patient subsequently underwent a MRgFUS thalamotomy, which induced an immediate and marked reduction in both the postural and kinetic tremor components, with minor complications (left upper lip hypesthesia, dysmetria in her left hand, and slight gait ataxia). The MRgFUS-induced lesion was centered more medially than the GKRS-induced lesion and extended more posteriorly and inferiorly. The MRgFUS-induced lesion interrupted remaining fibers of the dentatorubrothalamic tract (DRTT). The functional improvement 1-year post-MRgFUS was significant due to a marked reduction of the patient's kinetic tremor. The QoL score (Quality of Life in Essential Tremor) improved by 88% and her Clinical Rating Scale for Tremor left hand score by 62%. The side effects persisted but were minor, with no impact on her QoL. The explanation for the superior efficacy of MRgFUS compared to GKRS in our patient could be due to either a poor response to the GKRS or to a better localization of the MRgFUS lesion with a more extensive interruption of DRTT fibers. In conclusion, MRgFUS can be a valuable therapeutic option after unsatisfactory GKRS, especially because MRgFUS has immediate clinical effectiveness, allowing intra-procedural test lesions and possible readjustment of the target if necessary.

[Dementia with Lewy bodies: state of the art and perspectives for the clinician]. / Démence à corps de Lewy : état de l'art et perspectives pour le clinicien.

Dementia with Lewy bodies (DLB) is one of the most common causes of dementia, after Alzheimer's disease (AD) and vascular dementia. Its diagnosis remains a challenge for the clinician because of the variety of clinical presentations and comorbidities. The diagnosis is based on clinical criteria such as cognitive fluctuations, visual hallucinations, progressive cognitive impairment, Parkinsonian signs and REM sleep behavioral disorder. Although not specific, biomarkers are helpful for increasing the likelihood of LBD diagnosis and for differentiating LBD from other differential diagnoses such as Parkinson's disease with dementia and Alzheimer's disease. Clinicians should be aware of LBD clinical features and actively look for them in patients with cognitive symptoms, take into consideration the often-associated co-pathologies and to optimize patient's management.

La démence à corps de Lewy (DCL) est l'une des démences les plus fréquentes, après la maladie d'Alzheimer (MA) et la démence vasculaire. Son diagnostic est un défi pour le clinicien du fait de la variété des présentations cliniques et des comorbidités. Le diagnostic repose sur des critères cliniques comme des fluctuations cognitives, des hallucinations visuelles, des troubles cognitifs progressifs, des signes parkinsoniens et un trouble comportemental du sommeil paradoxal. L'utilisation des biomarqueurs, bien que non spécifiques, permet d'augmenter la probabilité de diagnostic de la DCL et de la différencier de la maladie de Parkinson avec démence et de la MA. De ce fait, devant tout sujet âgé avec trouble cognitif, une recherche des symptômes de la DCL est à réaliser en considérant aussi les traitements iatrogènes et les copathologies.

Dyskinesia-inducing lead contacts optimize outcome of subthalamic stimulation in Parkinson's disease.

BACKGROUND: Acute dyskinesias elicited by STN-DBS, here referred to as stimulation-induced dyskinesias, predict optimal clinical outcome in PD. However, it remains elusive whether stimulation-induced dyskinesias can guide DBS programming. OBJECTIVES: Here, we characterized stimulation-induced dyskinesias clinically and anatomically. We then tested whether dyskinesia-inducing contacts could be effectively programmed using independent current source technology. METHODS: We characterized stimulation-induced dyskinesias with directional and ring stimulation retrospectively in 20 patients. We then localized dyskinesia-inducing contacts by imaging coregistration and eventually programmed those contacts. RESULTS: We elicited dyskinesias in half of our patients. Dyskinesia-inducing contacts were mainly directional and were all located ventrally within the dorsolateral motor STN. When these dyskinesia-inducing contacts were programmed using independent current source technology, dyskinesia disappeared and robust antibradykinetic effects were obtained. CONCLUSION: We confirm that stimulation-induced dyskinesias are helpful clinical observations, which may guide programming of directional STN-DBS in PD. © 2019 International Parkinson and Movement Disorder Society.

Short pulse width in subthalamic stimulation in Parkinson's disease: a randomized, double-blind study.

BACKGROUND: We investigated the acute effect of short pulse widths on the therapeutic window in subthalamic nucleus deep brain stimulation in Parkinson's disease. METHODS: We assessed 10 PD patients with STN-DBS at a 60-µs pulse width. We randomly and double-blindedly applied 10- to 50-µs pulse widths. The principal outcome was the therapeutic window (difference between the amplitude thresholds for visible muscle contraction and for best rigidity control). The secondary outcome was the charge per pulse (which reflects the efficiency of the stimulation) needed to control rigidity. Two-way analysis of variance and pairwise t tests were applied. RESULTS: The therapeutic window widened when the pulse width shortened (r = -0.45; P < 0.001), and charge per pulse was reduced (P < 0.05). CONCLUSIONS: This randomized, double-blind study showed that shorter pulse widths widen the therapeutic window of STN-DBS in PD without increasing the electrical charge required to obtain the same acute clinical benefit. © 2017 International Parkinson and Movement Disorder Society.

Hyperdopaminergic behavioral spectrum in Parkinson's disease: A review.

Impulse control disorders (ICDs) and other related behaviors, such as punding and dopamine dysregulation syndrome, are frequent yet underrecognized non-motor complications of dopamine replacement therapy (DRT) in Parkinson's disease (PD); they can also have a major negative impact on quality of life. They result from complex interactions between a given individual's predispositions, non-physiological dopaminergic stimulation and PD pathology. Also, sensitization of the mesocorticolimbic pathway, reflected by the psychotropic effects of dopaminergic treatment, plays a crucial role in the emergence of these addictive behaviors. While early detection of changes in behavior, less use of dopamine agonists (DA) that have a relative selectivity for mesocorticolimbic dopamine receptors, and fractionation of levodopa dosages to avoid non-physiological pulsatile stimulation of dopamine receptors are key strategies in the management of this hyperdopaminergic behavioral spectrum, other complementary approaches are also addressed in this review.

[Movement disorders emergencies]. / Mouvements anormaux aux urgences.

Unlike most basal ganglia disorders, which usually progress slowly and relentlessly, a number of movement disorders may develop as acute or subacute conditions. Their occurrence commonly prompts patients to rush into the emergency room. A proper diagnosis is not always straightforward and requires a detailed analysis of the movement disorder phenomenology and a thorough medication screening, as many of these acute situations may be iatrogenic and drug-related. An accurate identification of the problem may enable an effective management and an appropriate therapy. This article is an overview of three distinct movement disorder emergencies, namely acute dystonia, acute chorea, and acute complications that can be observed in Parkinson's disease. Each topic is illustrated with a case report.

Contrairement à la plupart des affections des ganglions de la base, qui évoluent généralement sur un mode lentement progressif, certains mouvements anormaux peuvent se développer sur un mode aigu ou subaigu, amenant les patients à consulter en urgence. Le diagnostic est souvent délicat. Il repose sur une analyse détaillée de la phénoménologie et une anamnèse médicamenteuse fouillée, dans la mesure où ces situations sont volontiers iatrogènes. Une identification correcte du problème permet souvent une thérapeutique efficace. Le présent article propose une mise au point de trois problématiques de ce type, à savoir la dystonie aiguë, la chorée aiguë et les complications aiguës que l'on peut observer dans la maladie de Parkinson. Chaque sujet est illustré par un cas clinique.

[Advanced Parkinson's disease : indication for complex treatments]. / Maladie de Parkinson au stade avancé : indication aux traitements complexes.

Advanced Parkinson's disease (PD) is characterized by severe motor and non-motor complications that negatively impact on patients' autonomy and health-related quality of life. In early disease, the therapeutic strategy consists of gradual increase in dopaminergic treatment and levodopa dose fragmentation. In more advanced stages, this approach becomes insufficient and three therapeutic options can be considered: deep brain stimulation (DBS), continuous subcutaneous apomorphine infusion, and continuous levodopa/carbidopa intestinal gel infusion.

La maladie de Parkinson (MP) avancée est caractérisée par la présence de complications motrices et non motrices qui ont un impact significatif sur l'autonomie et la qualité de vie des patients. La stratégie thérapeutique consiste à fractionner le traitement dopaminergique, à recourir aux formes à libération prolongée, et aux inhibiteurs des enzymes de dégradation de la dopamine. Lorsque ces mesures sont insuffisantes, trois options thérapeutiques plus invasives peuvent être envisagées : la stimulation cérébrale profonde, la perfusion sous-cutanée continue d'apomorphine et l'administration intrajéjunale de gel de lévodopa/carbidopa. L'objectif de cet article est de décrire les indications, bénéfices et effets secondaires potentiels de ces traitements dits « complexes ¼.

Subthalamic stimulation may inhibit the beneficial effects of levodopa on akinesia and gait.

BACKGROUND: Gait and akinesia deterioration in PD patients during the immediate postoperative period of DBS has been directly related to stimulation in the subthalamic region. The underlying mechanisms remain poorly understood. The aim of the present study was to clinically and anatomically describe this side effect. METHODS: PD patients presenting with a worsening of gait and/or akinesia following STN-DBS, that was reversible on stimulation arrest were included. The evaluation included (1) a Stand Walk Sit Test during a monopolar survey of each electrode in the on-drug condition; (2) a 5-condition test with the following conditions: off-drug/off-DBS, off-drug/on-best-compromise-DBS, on-drug/off-DBS, on-drug/on-best-compromise-DBS, and on-drug/on-worsening-DBS, which utilized the contact inducing the most prominent gait deterioration. The following scales were performed: UPDRSIII subscores, Stand Walk Sit Test, and dyskinesia and freezing of gait scales. Localization of contacts was performed using a coregistration method. RESULTS: Twelve of 17 patients underwent the complete evaluation. Stimulation of the most proximal contacts significantly slowed down the Stand Walk Sit Test. The on-drug/on-worsening-DBS condition compared with the on-drug/off-DBS condition worsened akinesia (P = 0.02), Stand Walk Sit Test (P = 0.001), freezing of gait (P = 0.02), and improved dyskinesias (P = 0.003). Compared with the off-drug/off-DBS condition, the on-drug/on-worsening-DBS condition improved rigidity (P = 0.007) and tremor (P = 0.007). Worsening contact sites were predominantly dorsal and anterior to the STN in the anterior zona incerta and Forel fields H2. CONCLUSIONS: A paradoxical deterioration of gait and akinesia is a rare side effect following STN-DBS. We propose that this may be related to misplaced contacts, and we discuss the pathophysiology and strategies to identify and manage this complication. © 2016 International Parkinson and Movement Disorder Society.

[Deep brain stimulation for movement disorders: indications, results and complications]. / Stimulation cérébrale profonde lors de maladie de Parkinson et autres troubles du mouvement: indications, résultats et complications.

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.

[Trajectory of a patient with deep brain stimulation (DBS)]. / Stimulation cérébrale profonde: trajectoire du patient.

An eligibility assessment for deep brain stimulation is performed in order to select patients who are likely to benefit from it. Parkinson's patients have to stop dopaminergic drugs the day before surgery. During the operation, the patient must remain awake for recording of neuronal activity and for test stimulations to optimize the position of the electrodes. Postoperatively, the stimulation is increased progressively in parallel with a decrease of dopaminergic treatments. After about ten days, the patient can return to home and controls continue as an outpatient. Three months postoperatively, a complete testing of the neurostimulator is performed and at the one year follow-up visit, the effectiveness of the DBS is assessed.

Electroencephalographic Abnormalities in a Patient Suffering from Long-Term Neuropsychological Complications following SARS-CoV-2 Infection.

Introduction: Emotional apathy has recently been identified as a common symptom of long COVID. While recent meta-analyses have demonstrated generalized EEG slowing with the emergence of delta rhythms in patients hospitalized for severe SARS-CoV-2 infection, no EEG study or dopamine transporter scintigraphy (DaTSCAN) has been performed in patients with long COVID presenting with apathy. The objective of this case report was to explore the pathophysiology of neuropsychological symptoms in long COVID. Case Presentation: A 47-year-old patient who developed a long COVID with prominent apathy following an initially clinically mild SARS-CoV-2 infection underwent neuropsychological assessment, cerebral MRI, DaTSCAN, and resting-state high-density EEG 7 months after SARS-CoV-2 infection. The EEG data were compared to those of 21 healthy participants. The patient presented with apathy, cognitive difficulties with dysexecutive syndrome, moderate attentional and verbal episodic memory disturbances, and resolution of premorbid mild gaming disorder, mild mood disturbances, and sleep disturbances. His MRI and DaTSCAN were unremarkable. EEG revealed a complex pattern of oscillatory abnormalities compared to the control group, with a strong increase in whole-scalp delta and beta band activity, as well as a decrease in alpha band activity. Overall, these effects were more prominent in the frontal-central-temporal region. Conclusion: These results suggest widespread changes in EEG oscillatory patterns in a patient with long COVID characterized by neuropsychological complications with prominent apathy. Despite the inherent limitations of a case report, these results suggest dysfunction in the cortical networks involved in motivation and emotion.

Levodopa does not change cerebral vasoreactivity in Parkinson's disease.

The aim of this work was to study cerebral vasoreactivity to hypercapnia in Parkinson's disease (PD) before and after levodopa administration. The prospective study was conducted in 20 patients presenting with PD, using 3T blood oxygenation level-dependent (BOLD) functional MRI (fMRI) covering the whole brain. The hypercapnic stimulus was block-designed using carbogen inhalation, a gas mixture of 7% CO2 and 93% O2, before (OFF) and 60 minutes after administration of a suprathreshold (120%) therapeutic L-dopa dose (ON). Ten age-matched controls were enrolled for between-group comparisons. Analyses were conducted with a random effects model and corrected for multiple comparisons. No adverse reaction to the hypercapnic stimulus was reported. However, 10 patients and 2 controls were excluded because of incomplete protocol realization, inappropriate hypercapnic stimulus, or excessive movements, leaving 10 patients and 8 controls for further analyses. The hypercapnic stimulus increased whole-brain BOLD signal of 1.48% ± 0.06% (mean ± standard error) in controls, 1.59% ± 0.05% in patients OFF, and 1.62% ± 0.09% in patients ON. Regions of interest analyses showed a signal increase in gray matter of 2.60% ± 0.16% in controls, 2.89% ± 0.21% in patients OFF, and 2.87% ± 0.12% in patients ON. No global or regional significant difference was detected, when comparing patients OFF and ON L-dopa, or between patients and controls. Contrary to Alzheimer's disease, the vasoreactivity to hypercapnia was normal in PD before and after L-dopa administration, compared to controls. This negative result is an important finding, especially for neuroscientists using fMRI to investigate motricity and cognition, discarding a significant confounding effect.

Validation of Lead-DBS ß-Oscillation Localization with Directional Electrodes.

In deep brain stimulation (DBS) studies in patients with Parkinson's disease, the Lead-DBS toolbox allows the reconstruction of the location of ß-oscillations in the subthalamic nucleus (STN) using Vercise Cartesia directional electrodes (Boston Scientific). The objective was to compare these probabilistic locations with those of intraoperative monopolar ß-oscillations computed from local field potentials (0.5-3 kHz) recorded by using shielded single wires and an extracranial shielded reference electrode. For each electrode contact, power spectral densities of the ß-band (13-31 Hz) were compared with those of all eight electrode contacts on the directional electrodes. The DBS Intrinsic Template AtLas (DISTAL), electrophysiological, and DBS target atlases of the Lead-DBS toolbox were applied to the reconstructed electrodes from preoperative MRI and postoperative CT. Thirty-six electrodes (20 patients: 7 females, 13 males; both STN electrodes for 16 of 20 patients; one single STN electrode for 4 of 20 patients) were analyzed. Stimulation sites both dorsal and/or lateral to the sensorimotor STN were the most efficient. In 33 out of 36 electrodes, at least one contact was measured with stronger ß-oscillations, including 23 electrodes running through or touching the ventral subpart of the ß-oscillations' probabilistic volume, while 10 did not touch it but were adjacent to this volume; in 3 out of 36 electrodes, no contact was found with ß-oscillations and all 3 were distant from this volume. Monopolar local field potentials confirmed the ventral subpart of the probabilistic ß-oscillations.

Geospatial analysis of individual-based Parkinson's disease data supports a link with air pollution: A case-control study.

BACKGROUND: The etiology of Parkinson's disease (PD) remains unknown. To approach the issue of PD's risk factors from a new perspective, we hypothesized that coupling the geographic distribution of PD with spatial statistics may provide new insights into environmental epidemiology research. The aim of this case-control study was to examine the spatial dependence of PD prevalence in the Canton of Geneva, Switzerland (population = 474,211). METHODS: PD cases were identified through Geneva University Hospitals, private neurologists and nursing homes medical records (n = 1115). Controls derived from a population-based study (n = 12,614) and a comprehensive population census dataset (n = 237,771). All individuals were geographically localized based on their place of residence. Spatial Getis-Ord Gi* statistics were used to identify clusters of high versus low disease prevalence. Confounder-adjustment was performed for age, sex, nationality and income. Tukey's honestly significant difference was used to determine whether nitrogen dioxide and particulate matters PM10 concentrations were different within PD hotspots, coldspots or neutral areas. RESULTS: Confounder-adjustment greatly reduced greatly the spatial association. Characteristics of the geographic space influenced PD prevalence in 6% of patients. PD hotspots were concentrated in the urban centre. There was a significant difference in mean annual nitrogen dioxide and PM10 levels (+3.6 µg/m3 [p < 0.001] and +0.63 µg/m3 [p < 0.001] respectively) between PD hotspots and coldspots. CONCLUSION: PD prevalence exhibited a spatial dependence for a small but significant proportion of patients. A positive association was detected between PD clusters and air pollution. Our data emphasize the multifactorial nature of PD and support a link between PD and air pollution.

Oral Dysbiosis and Inflammation in Parkinson's Disease.

BACKGROUND: Oral microbiota has largely escaped attention in Parkinson's disease (PD), despite its pivotal role in maintaining oral and systemic health. OBJECTIVE: The aim of our study was to examine the composition of the oral microbiota and the degree of oral inflammation in PD. METHODS: Twenty PD patients were compared to 20 healthy controls. Neurological, periodontal and dental examinations were performed as well as dental scaling and gingival crevicular fluid sampling for cytokines measurement (interleukine (IL)-1ß, IL-6, IL-1 receptor antagonist (RA), interferon-γ and tumor necrosis factor (TNF)-α). Two months later, oral microbiota was sampled from saliva and subgingival dental plaque. A 16S rRNA gene amplicon sequencing was used to assess bacterial communities. RESULTS: PD patients were in the early and mid-stage phases of their disease (Hoehn & Yahr 2-2.5). Dental and periodontal parameters did not differ between groups. The levels of IL-1ß and IL-1RA were significantly increased in patients compared to controls with a trend for an increased level of TNF-α in patients. Both saliva and subgingival dental plaque microbiota differed between patients and controls. Streptococcus mutans, Kingella oralis, Actinomyces AFQC_s, Veillonella AFUJ_s, Scardovia, Lactobacillaceae, Negativicutes and Firmicutes were more abundant in patients, whereas Treponema KE332528_s, Lachnospiraceae AM420052_s, and phylum SR1 were less abundant. CONCLUSION: Our findings show that the oral microbiome is altered in early and mid-stage PD. Although PD patients had good dental and periodontal status, local inflammation was already present in the oral cavity. The relationship between oral dysbiosis, inflammation and the pathogenesis of PD requires further study.

Extrastriatal 123I-FP-CIT SPECT impairment in degenerative parkinsonisms.

INTRODUCTION: Neuropathological data and nuclear medicine imaging show extensive serotonergic impairment in Parkinson's disease (PD) and atypical parkinsonian syndromes (APS). The study aims at performing a case-controlled region-of-interest (ROI)-based analysis of 123I-N-ω-fluoropropyl-2ß-carbomethoxy-3ß-(4-iodophenyl) nortropane (123I-FP-CIT) images to measure extrastriatal regional deficits in PD and APS, and assess their added diagnostic value in discriminating degenerative parkinsonisms from other conditions. METHODS: We included 157 patients with early degenerative parkinsonism (mean age 72.6 years, 44% female, mean disease duration at scan 1.6 years), i.e. PD (n = 59), multiple system atrophy parkinsonian variant (MSA-P, n = 17), progressive supranuclear palsy (PSP, n = 28), corticobasal syndrome (CBS, n = 19), dementia with Lewy bodies (DLB, n = 34) as well as 58 similarly-aged control participants. 123I-FP-CIT SPECT images were processed with statistical parametric mapping 12 (SPM12)-based PETPVE12 software and subjected to partial volume effect correction for ROI-based group comparisons. RESULTS: Relative to controls, all forms of degenerative parkinsonism showed decreased 123I-FP-CIT uptake in caudate nucleus, putamen but also pallidum and insula. In addition, a significant uptake reduction was observed in thalamus for MSA-P and PSP, in midbrain for PD and PSP, and in the amygdala for PSP (ANCOVA controlling for age, sex and antidepressant medication, all Bonferroni-corrected p < 0.007). Receiver-operating characteristics area-under-the-curve showed that adding extrastriatal evaluation led to higher accuracies in separating degenerative conditions from control participants (96.1% vs 94.9% with striatal ROIs only, p = 0.045). CONCLUSION: This study provides evidence of a major extrastriatal 123I-FP-CIT impairment, and therefore of an altered serotonergic transmission in PD and APS, confirming previous neuropathological and SERT imaging findings.

Embarrassment and Shame in People With Parkinson's Disease: A New Tool for Self-Assessment.

Shame and embarrassment related to Parkinson's disease (PD) are rarely addressed in clinical practice nor studied in neuroscience research, partly because no specific tool exists to detect them in PD. Objective: To develop a self-applied assessment tool of shame and embarrassment specifically related to PD or its treatment, to promptly identify the presence and severity of these two emotions in PD. Methods: Identification and selection of relevant items were obtained from the collection of PD patients' opinions during support groups and interviews. Several further items were added following a literature review. Subsequently, a two-phase pilot study was performed for identification of ambiguous items and omissions, and to obtain preliminary data on acceptability, reliability, validity and relevance of the new scale (SPARK). Results: A total of 105 PD patients were enrolled in the study. Embarrassment was reported in 85% of patients, while shame was present in 26%. Fifteen percent of patients did not describe any shame or embarrassment. On average, the intensity of these two emotions was low with a marked floor effect in SPARK items and subscales. However, SPARK total score inter-individual variability was important (range 1-84 out of 99). Acceptability and quality of data were satisfactory with no floor or ceiling effects (2.9% each) or missing data. Internal consistency (Cronbach's alpha) was 0.94 for total score and 0.73-0.87 for subscales. The scale correlated ≥0.60 with instruments measuring related constructs. Content validity was satisfactory. SPARK total score strongly correlated with impaired health-related quality of life (rS = 0.81), the propensity to feel embarrassed or ashamed (rS = 0.68 and 0.66, respectively), and anxiety (rS = 0.72) and depression (rS = 0.63) levels. Moderate to high correlations were observed between SPARK total score and apathy (rS = 0.46) and a more pronounced personality trait directed toward harm avoidance (rS = 0.46). No significant differences in SPARK scores were found by sex, education level, PD duration, Hoehn and Yahr stages or PD phenotype. Conclusion: Preliminary analysis of psychometric properties suggests that SPARK could be an acceptable and reliable instrument for assessing shame and embarrassment in PD. SPARK could help healthcare professionals to identify and characterize PD-induced shame and embarrassment.