Nicolas Jodoin

Somatodendritic localization of 5-HT1A and preterminal axonal localization of 5-HT1B serotonin receptors in adult rat brain

The 5‐HT1A and 5‐HT1B receptors of serotonin play important roles as auto‐ and heteroreceptors controlling the release of serotonin itself and of other neurotransmitters/modulators in the central nervous system (CNS). To determine the precise localization of these receptors, we examined their respective cellular and subcellular distributions in the nucleus raphe dorsalis and hippocampal formation (5‐HT1A) and in the globus pallidus and substantia nigra (5‐HT1B), using light and electron microscopic immunocytochemistry with specific antibodies. Both immunogold and immunoperoxidase preembedding labelings were achieved. In the nucleus raphe dorsalis, 5‐HT1A immunoreactivity was found exclusively on neuronal cell bodies and dendrites, and mostly along extrasynaptic portions of their plasma membrane. After immunogold labeling, the density of membrane‐associated 5‐HT1A receptors could be estimated to be at least 30–40 times that in the cytoplasm. In the hippocampal formation, the somata as well as dendrites of pyramidal and granule cells displayed 5‐HT1A immunoreactivity, which was also prominent on the dendritic spines of pyramidal cells. In both substantia nigra and globus pallidus, 5‐HT1B receptors were preferentially associated with the membrane of fine, unmyelinated, preterminal axons, and were not found on axon terminals. A selective localization to the cytoplasm of endothelial cells of microvessels was also observed. Because the 5‐HT1A receptors are somatodendritic, they are ideally situated to mediate serotonin effects on neuronal firing, both as auto‐ and as heteroreceptors. The localization of 5‐HT1B receptors to the membrane of preterminal axons suggests that they control transmitter release from nonserotonin as well as serotonin neurons by mediating serotonin effects on axonal conduction. The fact that these two receptor subtypes predominate at extrasynaptic and nonsynaptic sites provides further evidence for diffuse serotonin transmission in the CNS. J. Comp. Neurol. 417:181–194, 2000. ©2000 Wiley‐Liss, Inc.

Investigation of C9orf72 repeat expansions in Parkinson's disease

Large repeat expansions in the C9orf72 gene were recently reported to be a major cause of familial amyotrophic lateral sclerosis and frontotemporal dementia. Given some of the clinical and pathologic overlap between these 2 diseases and Parkinsons disease, we sought to evaluate the presence of these expansions in a cohort of French-Canadian patients with Parkinsons disease. No pathologic expansion was found in our cohort of patients suggesting that C9orf72 repeat expansions do not play a major role in the pathogenesis of Parkinsons disease.

Magnetic resonance imaging lesion pattern in Guadeloupean parkinsonism is distinct from progressive supranuclear palsy

In the Caribbean island of Guadeloupe, patients with atypical parkinsonism develop a progressive supranuclear palsy-like syndrome, named Guadeloupean parkinsonism. Unlike the classical forms of progressive supranuclear palsy, they develop hallucinations and myoclonus. As lesions associated with Guadeloupean parkinsonism are poorly characterized, it is not known to what extent they differ from progressive supranuclear palsy. The aim of the present study was to determine the structural and metabolic profiles of Guadeloupean parkinsonism compared with progressive supranuclear palsy and controls using combined structural and diffusion magnetic resonance imaging and magnetic resonance spectroscopy. We included 9 patients with Guadeloupean parkinsonism, 10 with progressive supranuclear palsy and 9 age-matched controls. Magnetic resonance imaging examination was performed at 1.5 T and included 3D T(1)-weighted and fluid-attenuated inversion recovery images, diffusion tensor imaging and single voxel magnetic resonance spectroscopy in the lenticular nucleus. Images were analysed using voxel-based morphometry, voxel-based diffusion tensor imaging and brainstem region of interest measurements. In patients with Guadeloupean parkinsonism, structural and diffusion changes predominated in the temporal and occipital lobes, the limbic areas (medial temporal, orbitofrontal and cingulate cortices) and the cerebellum. In contrast to patients with progressive supranuclear palsy, structural changes predominated in the midbrain and the basal ganglia and diffusion abnormalities predominated in the frontocentral white matter, the basal ganglia and the brainstem. Compared with controls, the N-acetylaspartate to creatinine ratio was decreased in patients with progressive supranuclear palsy and to a lesser extent in patients with Guadeloupean parkinsonism. The pattern of structural and diffusion abnormalities differed between progressive supranuclear palsy and Guadeloupean parkinsonism. Widespread cortical atrophy was observed in patients with Guadeloupean parkinsonism who presented marked cognitive changes and hallucinations, whereas midbrain lesions were less severe than in progressive supranuclear palsy. Midbrain (progressive supranuclear palsy) or cortical (Guadeloupean parkinsonism) atrophy was a distinctive neuroimaging feature for differential diagnosis.

Does unilateral basal ganglia activity functionally influence the contralateral side? What we can learn from STN stimulation in patients with Parkinson's disease

In humans, the control of voluntary movement, in which the corticobasal ganglia (BG) circuitry participates, is mainly lateralized. However, several studies have suggested that both the contralateral and ipsilateral BG systems are implicated during unilateral movement. Bilateral improvement of motor signs in patients with Parkinsons disease (PD) has been reported with unilateral lesion or high-frequency stimulation (HFS) of the internal part of the globus pallidus or the subthalamic nucleus (STN-HFS). To decipher the mechanisms of production of ipsilateral movements induced by the modulation of unilateral BG circuitry activity, we recorded left STN neuronal activity during right STN-HFS in PD patients operated for bilateral deep brain stimulation. Left STN single cells were recorded in the operating room during right STN-HFS while patients experienced, or did not experience, right stimulation-induced dyskinesias. Most of the left-side STN neurons (64%) associated with the presence of right dyskinesias were inhibited, with a significant decrease in burst and intraburst frequencies. In contrast, left STN neurons not associated with right dyskinesias were mainly activated (48%), with a predominant increase 4-5 ms after the stimulation pulse and a decrease in oscillatory activity. This suggests that unilateral neuronal STN modulation is associated with changes in the activity of the contralateral STN. The fact that one side of the BG system can influence the functioning of the other could explain the occurrence of bilateral dyskinesias and motor improvement observed in PD patients during unilateral STN-HFS, as a result of a bilateral disruption of the pathological activity in the corticosubcortical circuitry.

Pallidal activity in myoclonus dystonia correlates with motor signs.

Myoclonus–dystonia related to epsilon‐sarcoglycan gene mutations is characterized by myoclonic jerks and mild to moderate dystonia. The role of basal ganglia dysfunction in the pathogenesis is unknown.

Increased Prevalence of Non-motor Symptoms in Essential Tremor

Background Cases with essential tremor (ET) have been described with Lewy body inclusions, the hallmark of Parkinson disease (PD). Patients with PD may suffer from anosmia, depression, constipation, and rapid eye movement sleep behavior disorder (RBD), sometimes years before the appearance of their motor syndrome. The objective of this study was to evaluate the prevalence of these non-motor Parkinsons associated symptoms in patients with ET. Methods Fifty ET subjects were contacted by phone and given questionnaires evaluating the presence or absence of anosmia, depression, constipation, and RBD. Frequencies of these symptoms were compared with their published prevalence in the general population. Results Of the patients with ET, 4.5% reported having anosmia or hyposmia and 21.7% reported being constipated, similar to what is observed in the general population. Using a screening questionnaire for RBD, 43.5% of ET patients are possibly suffering from RBD, whereas in the general population prevalence is estimated to be 0.5%. Finally, depression was detected in 21.7% of ET patients; in the general population, prevalence is 5%. Discussion Patients with ET seem to have more RBD and more depression than found in the general population. Prospective studies with normal control groups are needed to confirm these findings.

Subthalamic stimulation improves motor function but not home and neighborhood mobility

Subthalamic (STN) deep brain stimulation (DBS) is a recognized therapy for alleviating motor symptoms of Parkinsons disease (PD). However, little is known about its impact on mobility, an important component of quality of life (QoL). To address this issue, we assessed the impact of STN DBS on life‐space mobility and QoL.

Characterization of Burning Mouth Syndrome in Patients with Parkinson's Disease.

AIMS To determine the prevalence and characteristics of burning mouth syndrome (BMS) in a Parkinsons disease (PD) population through a self-administered, custom-made survey. METHODS A total of 218 surveys were collected during regular outpatient visits at two Movement Disorders Clinics in Montreal (Canada) and Toulouse (France) to gather information about pain experience, PD-related symptoms, and oral and general health. A neurologist confirmed the diagnosis of PD, drug treatment, Hoehn-Yahr stage, and Schwab & England Activity of Daily Living score. Data between groups were compared using the independent samples Mann-Whitney U test and two-sided exact Fisher test. RESULTS Data from 203 surveys were analyzed. BMS was reported by eight subjects (seven females and one male), resulting in a prevalence of 4.0% (95% confidence interval [CI] = 2.1-7.8). Five participants with chronic nonburning oral pain were excluded. PD severity and levodopa equivalent daily dose did not differ between non-BMS and BMS participants. Mean poor oral health index was higher in BMS compared to non-BMS subjects (49.0 vs 32.2 points, P < .05). BMS manifested after PD onset in seven patients, did not occur on a daily basis in four, and always coexisted with restless legs syndrome. CONCLUSION This survey yielded a low prevalence of BMS in PD patients, indicating no strong link between the two conditions. An augmenting effect such as that resulting from drug treatment in restless legs syndrome or sensory neuropathy cannot be excluded.

Enteral Feeding Using Levodopa‐Carbidopa Intestinal Gel Percutaneous Endoscopic Gastrostomy Tube

In Parkinson’s disease (PD), dysphagia has a significant influence on nutritional status. When dysphagia is resistant to oral nutrition intervention, enteral nutrition using a percutaneous endoscopic gastrostomy (PEG) can be considered. A levodopa (L-DOPA)-carbidopa intestinal gel (LCIG) has been used to treat advanced PD using a PEG with a jejunal extension (PEG-J) (AbbVie, Montr eal, Canada). We present a case in which the LCIG PEG-J was used successfully for feeding.