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Cowden syndrome (CS) is an autosomal dominant syndrome characterized by the development of hamartomas and an increased cancer risk. Most CS patients harbor mutations in the phosphatase and tensin homolog (PTEN) gene. We herein report a 70-year-old patient with CS who presented with lower extremity weakness caused by multiple thoracic dural arteriovenous fistulas. Genetic testing revealed a truncated PTEN mutation (c.485_487delACAinsCC and p.D162Afs*5). Vascular malformations are common in CS, particularly in the extremities. However, spinal dural arteriovenous fistulas (AVFs) are extremely rare. Furthermore, in our case, the number of AVFs increased, and both lower limbs became flaccid four months after embolization. Therefore, we suggest that physicians carefully observe the changes in symptoms for prolonged periods after embolization.
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BACKGROUND: Safinamide is an effective adjunctive therapy for wearing-off in Parkinson's disease (PD); however, evidence is lacking in older patients and those in the early stages of wearing-off. This study evaluated the efficacy and safety of safinamide as adjunctive therapy in patients with PD treated with levodopa monotherapy in clinical practice. METHODS: This multicentre, open-label observational study was conducted at five sites in Japan. Patients diagnosed with PD and wearing-off initiated safinamide as adjunctive therapy with levodopa monotherapy. Efficacy endpoints were mean changes in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I, III, and IV scores; daily ON-time without dyskinesia using 24-h patient symptom diaries; and 39-item Parkinson's Disease Questionnaire (PDQ-39) scores at 18 weeks of treatment. RESULTS: In total, 24 patients initiated safinamide (66.7% were aged ≥75 years); the mean duration of wearing-off was 1.2 years. MDS-UPDRS Part III total score, Part IV total score, and PDQ-39 summary index decreased significantly from baseline (mean change -7.0 [p = 0.012], -2.4 [p = 0.007] and - 5.3 [p = 0.012], respectively). There was a non-statistically significant increase of 1.55 h in mean daily ON-time without dyskinesia. Numerical Rating Scale total score for pain (p = 0.015), and scores for OFF-period pain (p = 0.012) and nocturnal pain (p = 0.021) subdomains were significantly improved in the subgroup with pain. Most reported adverse events were classified as mild. CONCLUSION: Safinamide improved motor and non-motor symptoms and quality of life-related measures in older patients with PD in the early stages of wearing-off without new safety concerns. STUDY REGISTRATION: University Hospital Medical Information Network in Japan; study ID: UMIN000044341.
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Alanina , Antiparkinsonianos , Bencilaminas , Levodopa , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/tratamiento farmacológico , Masculino , Bencilaminas/uso terapéutico , Bencilaminas/efectos adversos , Femenino , Anciano , Levodopa/uso terapéutico , Levodopa/efectos adversos , Alanina/análogos & derivados , Alanina/uso terapéutico , Japón , Antiparkinsonianos/uso terapéutico , Antiparkinsonianos/efectos adversos , Persona de Mediana Edad , Resultado del Tratamiento , Quimioterapia Combinada , Anciano de 80 o más Años , Índice de Severidad de la Enfermedad , Pueblos del Este de AsiaRESUMEN
Levodopa-induced dyskinesia (LID) is a common complication in patients with advanced Parkinson's disease (PD) undergoing treatment with levodopa. Glutamate receptor antagonists can suppress LID; however, the underlying mechanisms remain unclear. Here, we aimed to evaluate the effect of 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP), a metabotropic glutamate receptor 5 (mGluR5) antagonist, on dyskinesia. We recorded the neuronal activity of the entopeduncular nucleus and examined responses to cortical electric stimulation in the control group (n = 6) and three groups of rats (male PD model). Saline was intraperitoneally administered to dopamine lesioned (DL) rats (n = 6), levodopa/benserazide (L/B) was administered to LID rats (n = 8), and L/B combined with MTEP was administered to MTEP rats (n = 6) twice daily for 14 days. We administered L/B to LID and MTEP rats 48 h after the final administration of MTEP to examine the chronic effect of MTEP. The control and DL groups did not have LID. The MTEP group had less LID than the LID group (p < .01) on day 1 and day 18. The control group had a typical triphasic pattern consisting of early excitation (early-Ex), inhibition, and late excitation (late-Ex). However, the inhibition phase disappeared, was partially observed, and was fully suppressed in the DL, LID, and MTEP groups, respectively. The cortico-striato-entopeduncular pathway is important in the pathophysiology of LID. mGluR5 antagonism suppresses LID progression by preventing physiological changes in the cortico-striato-entopeduncular pathway. Future studies are required to validate these results.
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Discinesia Inducida por Medicamentos , Enfermedad de Parkinson , Humanos , Ratas , Masculino , Animales , Levodopa/efectos adversos , Enfermedad de Parkinson/tratamiento farmacológico , Receptor del Glutamato Metabotropico 5 , Antiparkinsonianos/efectos adversos , Discinesia Inducida por Medicamentos/tratamiento farmacológico , Discinesia Inducida por Medicamentos/prevención & control , Discinesia Inducida por Medicamentos/metabolismo , OxidopaminaRESUMEN
INTRODUCTION: Monoamine oxidase type B inhibitors, including selegiline, are established as anti-Parkinsonian Drugs. Inhibition of monoamine oxidase type B enzymes might suppress the inflammation because of inhibition to generate reactive oxygen species. However, its effect on brain microstructure remains unclear. The aim of this study is to elucidate white matter and substantia nigra (SN) microstructural differences between Patients with Parkinson's disease with and without selegiline treatment by two independently recruited cohorts. METHODS: Diffusion tensor imaging and free water imaging indices of WM and SN were compared among 22/15 Patients with Parkinson's disease with selegiline (PDselegiline(+)), 33/23 Patients with Parkinson's disease without selegiline (PDselegiline(-)), and 25/20 controls, in the first/second cohorts. Two cohorts were analyzed with different MRI protocols. RESULTS: Diffusion tensor imaging and free-water indices of major white matter tracts were significantly differed between the PDselegiline(-) and controls in both cohorts, although not between the PDselegiline(+) and controls except for restricted areas. Compared with the PDselegiline(+), free-water was significantly higher in the PDselegiline(-) in the inferior fronto-occipital fasciculus, superior longitudinal fasciculus, and superior and posterior corona radiata (first cohort) and the forceps major and splenium of the corpus callosum (second cohort). There were no significant differences in free-water of anterior or posterior substantia nigra between PDselegiline(+) and PDselegiline(-). CONCLUSIONS: Selegiline treatment might reduce the white matter microstructural abnormalities detected by free-water imaging in Parkinson's disease.
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Enfermedad de Parkinson , Sustancia Blanca , Humanos , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/patología , Imagen de Difusión Tensora , Selegilina/uso terapéutico , Imagen de Difusión por Resonancia Magnética , Imagen por Resonancia Magnética , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Agua , MonoaminooxidasaRESUMEN
BACKGROUND: Chronic constipation is a common digestive complication of Parkinson's disease (PD). OBJECTIVES: To verify the usefulness of elobixibat, an ileal bile acid transporter inhibitor, for chronic constipation in PD. METHODS: This double-blind, placebo-controlled study consisted of a 2-week observation/washout period and a 4-week treatment period. All patients received a Bowel Movement Diary at Week -2 and were allocated to elobixibat (10 mg) or placebo at Week 0. Patients visited at Weeks 2 and 4 to report daily spontaneous bowel movements (SBM), stool form, drug use, quality of life (QOL), and safety. Changes in these parameters were assessed. RESULTS: The study included 38 patients in the elobixibat group and 39 in the placebo group, and 37 each completed the study. SBM frequency/week (mean ± standard deviation) increased significantly from 4.2 ± 2.6 at baseline to 5.9 ± 3.2 at Week 4 in the elobixibat group (P = 0.0079), but not in the placebo group (4.5 ± 2.7 to 5.3 ± 3.5; P = 0.0889). On analysis of covariance, the between-group difference in frequency changes at Week 4 (primary endpoint) was not significant after adjustment by baseline and sex (point estimate = 0.8; 95% confidence interval = -0.57 to 2.09, P = 0.2601), although a significant difference (P = 0.0011) was evidenced at Week 1 by a similar analysis. Stool form and scores of satisfaction and stigma were improved by elobixibat. Adverse events were as previously reported. CONCLUSIONS: Elobixibat improved the SBM frequency, though the defined primary endpoint was not evidenced. QOL parameters (stool consistency and treatment satisfaction) were also improved. Elobixibat may have therapeutic benefits in PD patients suffering from chronic constipation. TRIAL REGISTRATION INFORMATION: Trial Registration Number: JPRN-jRCTs031200172 (submitted: October 26, 2020; first patient enrolment: December 23, 2020; https://jrct.niph.go.jp/en-latest-detail/jRCTs031200172).
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Dipéptidos , Enfermedades Gastrointestinales , Enfermedad de Parkinson , Tiazepinas , Humanos , Enfermedad Crónica , Estreñimiento/tratamiento farmacológico , Enfermedad de Parkinson/complicaciones , Calidad de Vida , Método Doble CiegoRESUMEN
Hyperhomocysteinemia is an important risk factor for cerebral infarction. Herein, we report on a 30-year-old man previously diagnosed with epilepsy who presented with right hemiplegia and total aphasia. Magnetic resonance imaging showed a fronto-temporal ischemic lesion due to occlusion of the left middle cerebral artery. Clinical testing and imaging demonstrated that he had hyperhomocysteinemia induced by multiple factors including the C677T polymorphism on 5.10-methylenetetrahydrofolate reductase (MTHFR), and multiple vitamin deficiencies. The C677T polymorphism on MTHFR is closely related to hyperhomocysteinemia and folate deficiency in epileptic patients who are taking multiple anti-convulsants. Given hyperhomocysteinemia can independently cause stroke at a young age, physicians should periodically examine plasma homocysteine and serum folic acid levels in epileptic patients who are on long-term regimens of multiple anti-epileptic drugs.
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BACKGROUND: Dyskinesia frequently occurs during long-term treatment with levodopa in patients with Parkinson's disease (PD) and impacts quality of life. Few studies have examined risk factors for developing dyskinesia in PD patients exhibiting wearing-off. Therefore, we investigated the risk factors and impact of dyskinesia in PD patients exhibiting wearing-off. METHODS: We investigated the risk factors and impact of dyskinesia in a 1-year observational study of Japanese PD patients exhibiting wearing-off (J-FIRST). Risk factors were assessed by logistic regression analyses in patients without dyskinesia at study entry. Mixed-effect models were used to evaluate the impact of dyskinesia on changes in Movement Disorder Society-Unified PD Rating Scale (MDS-UPDRS) Part I and PD Questionnaire (PDQ)-8 scores from one timepoint before dyskinesia was observed. RESULTS: Of 996 patients analyzed, 450 had dyskinesia at baseline, 133 developed dyskinesia within 1 year, and 413 did not develop dyskinesia. Female sex (odds ratio [95% confidence interval]: 2.636 [1.645-4.223]) and administration of a dopamine agonist (1.840 [1.083-3.126]), a catechol-O-methyltransferase inhibitor (2.044 [1.285-3.250]), or zonisamide (1.869 [1.184-2.950]) were independent risk factors for dyskinesia onset. MDS-UPDRS Part I and PDQ-8 scores increased significantly after the onset of dyskinesia (least-squares mean change [standard error] at 52 weeks: 1.11 [0.52], P = 0.0336; 1.53 [0.48], P = 0.0014; respectively). CONCLUSION: Female sex and administration of a dopamine agonist, a catechol-O-methyltransferase inhibitor, or zonisamide were risk factors for dyskinesia onset within 1 year in PD patients exhibiting wearing-off. Nonmotor symptoms and quality of life deteriorated after dyskinesia onset.
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Discinesias , Enfermedad de Parkinson , Humanos , Femenino , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/epidemiología , Antiparkinsonianos/efectos adversos , Agonistas de Dopamina/efectos adversos , Catecol O-Metiltransferasa , Zonisamida , Calidad de Vida , Levodopa/efectos adversos , Discinesias/epidemiología , Discinesias/etiología , Factores de RiesgoRESUMEN
Sense of time (temporal sense) is believed to be processed by various brain regions in a complex manner, among which the basal ganglia, including the striatum and subthalamic nucleus (STN), play central roles. However, the precise mechanism for processing sense of time has not been clarified. To examine the role of the STN in temporal processing of the sense of time by directly manipulating STN function by switching a deep brain stimulation (DBS) device On/Off in 28 patients with Parkinson's disease undergoing STN-DBS therapy. The test session was performed approximately 20 min after switching the DBS device from On to Off or from Off to On. Temporal sense processing was assessed in three different tasks (time reproduction, time production, and bisection). In the three temporal cognitive tasks, switching STN-DBS to Off caused shorter durations to be produced compared with the switching to the On condition in the time production task. In contrast, no effect of STN-DBS was observed in the time bisection or time reproduction tasks. These findings suggest that the STN is involved in the representation process of time duration and that the role of the STN in the sense of time may be limited to the exteriorization of memories formed by experience.
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We report two rare cases. One involved acute calcific retropharyngeal tendinitis, an inflammatory condition of the longus colli tendon triggered by the deposition of calcium hydroxyapatite crystals. The other involved crowned dens syndrome, caused by pseudogout of the atlantoaxial junction following deposition of calcium pyrophosphate dehydrate or calcium hydroxyapatite. Although these two diseases involve different mechanisms, the common symptoms of neck pain and fever resemble those of meningitis. Accurate diagnosis can thus be difficult without background knowledge of these conditions. Cerebrospinal fluid examination and cervical computed tomography are useful for distinguishing these pathologies from meningitis.
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INTRODUCTION: Idiopathic rapid eye movement sleep behavior disorder (iRBD) is one of the most specific prodromal symptoms of synucleinopathies, including Parkinson's disease (PD) and multiple system atrophy. The Japan Parkinson's Progression Markers Initiative (J-PPMI) was a prospective cohort study conducted in Japanese patients with iRBD to investigate biomarkers for prodromal synucleinopathies. We carried out an initial assessment of the J-PPMI study to reveal the factors correlated with dopamine transporter single-photon emission computed tomography (DaT) and 123I-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy. METHODS: This cross-sectional study was conducted in 108 patients with iRBD, selected from the J-PPMI study. We divided the patients into four groups based on the MIBG and DaT results. We also recorded the patients' demographics and clinical data. Following PD probability calculation, we examined the biomarkers associated with DaT and MIBG. RESULTS: Ninety-five of the enrolled patients (88%) met the diagnostic criteria for prodromal PD based on the probability score. Only five patients had normal MIBG and DaT. We identified 29 cases with decreased DaT and MIBG, all of whom met the above diagnostic criteria. Both DaT and MIBG were significantly correlated with the Japanese version of the Montreal Cognitive Assessment (MoCA-J) score. CONCLUSION: Both DaT and MIBG are important biomarkers for confirming synucleinopathies and/or staging disease progression. Although 95% of iRBD patients were consistent with the body-first subtype concept, alpha-synuclein pathologies of iRBD might have widespread systemic involvement rather than being confined to the lower brainstem, particularly in patients with reduced MoCA-J scores.
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Enfermedad de Parkinson , Trastorno de la Conducta del Sueño REM , Sinucleinopatías , Humanos , Trastorno de la Conducta del Sueño REM/diagnóstico por imagen , Trastorno de la Conducta del Sueño REM/complicaciones , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática , 3-Yodobencilguanidina , Japón , alfa-Sinucleína , Estudios Transversales , Estudios Prospectivos , Enfermedad de Parkinson/complicaciones , BiomarcadoresRESUMEN
Background: The effects of subthalamic nuclear deep brain stimulation therapy (STN-DBS) and combined postoperative rehabilitation for patients with Parkinson's disease with postural instability have yet to be well reported. This study investigated the effects of short-term postoperative rehabilitation with STN-DBS on physical function in patients with Parkinson's disease. Methods: Patients diagnosed with Parkinson's disease who were admitted to our hospital for STN-DBS surgery were included in this study. Data were prospectively collected and retrospectively analyzed. Postoperative rehabilitation consisted of muscle-strengthening exercises, stretching, and balance exercises for 40-60 minutes per day for approximately 14 days. The Mini-Balance Evaluation Systems Test (Mini-BESTest), Timed Up and Go test (TUG) seconds and steps, Trunk Impairment Scale (TIS), seconds for 10 times toe-tapping, lower limb extension torque using StrengthErgo240, and center of pressure sway in the quiet standing posture were evaluated preoperatively, postoperatively, and at discharge. Mini-BESTest changes were also evaluated in the two groups classified by the presence or absence of postural instability. One-way and two-way repeated measures analyses of variance were performed for each of the three periods of change, and paired t-tests with the Bonferroni method were performed as multiple comparison tests. A stepwise multiple regression model was used to identify factors associated with balance improvement. Results: A total of 60 patients with Parkinson's disease were included, and there were significant increases in Mini-BESTest, TIS, StrengthErgo240, and postural sway during closed-eye standing compared to pre- and postoperative conditions at discharge (p < 0.05), and they decreased significantly compared to the postoperative period (p < 0.05). On stepwise multiple regression analysis, decreased steps of TUG and improvement of TIS scores were related to improvement of the Mini-BESTest (p < 0.05). In addition, Mini-BESTest scores in both groups with and without postural instability were significantly increased at discharge compared to preoperative and postoperative conditions (p < 0.01). Conclusion: Postoperative rehabilitation combined with STN-DBS may provide short-term improvements in physical function compared with the preoperative medicated status. The improvements in gait step length and trunk function may be important factors for obtaining improvement of postoperative postural stability.
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BACKGROUND: Impulse control behaviors (ICBs) in Parkinson's disease (PD) are thought to be caused by an overdose of dopaminergic therapy in the relatively spared ventral striatum, or by hypersensitivity of this region to dopamine. Alterations in brain networks are now also thought to contribute to the development of ICBs. OBJECTIVE: To comprehensively assess white matter microstructures in PD patients with ICBs using advanced diffusion MRI and magnetization transfer saturation (MT-sat) imaging. METHODS: This study included 19 PD patients with ICBs (PD-ICBs), 18 PD patients without ICBs (PD-nICBs), and 20 healthy controls (HCs). Indices of diffusion tensor imaging (DTI), diffusion kurtosis imaging, neurite orientation dispersion and density imaging, and MT-sat imaging were evaluated using tract-based spatial statistics (TBSS), regions of interest (ROIs), and tract-specific analysis (TSA). RESULTS: Compared with HCs, PD-nICBs had significant alterations in many major white matter tracts in most parameters. In contrast, PD-ICBs had only partial changes in several parameters. Compared with PD-ICBs, TBSS, ROI, and TSA analyses revealed that PD-nICBs had lower axial kurtosis, myelin volume fraction, and orientation dispersion index in the uncinate fasciculus and external capsule, as well as in the retrolenticular part of the internal capsule. These are components of the reward system and the visual and emotional perception areas, respectively. INTERPRETATION: Myelin and axonal changes in fibers related to the reward system and visual emotional recognition might be more prominent in PD-nICBs than in PD-ICBs.
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Enfermedad de Parkinson , Sustancia Blanca , Encéfalo/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética , Imagen de Difusión Tensora/métodos , Humanos , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/psicología , Sustancia Blanca/diagnóstico por imagenRESUMEN
INTRODUCTION: Chronic constipation worsens the quality of life (QOL) of patients with Parkinson's disease (PD). Elobixibat, an ileal bile acid transporter inhibitor, is a useful laxative, but its effect on chronic constipation in patients with PD remains unclear. Therefore, we designed a placebo-controlled, randomised, double-blind study to investigate the efficacy and safety of elobixibat in patients with PD with chronic constipation. METHODS AND ANALYSIS: The study will consist of 2-week observation and 4-week treatment periods. Patients with clinically established PD will record the status of spontaneous bowel movements and use of rescue medications/concomitant medications in a Bowel Movement Diary from the start of the observation period at visit 1 (week -2). At visit 2 (week 0), patients will be assessed for final registration based on the diary records and physical examinations, and allocated to either the elobixibat or placebo group. Daily intake of the investigational drug will be recorded in the diary. Patients will undergo laboratory tests and answer constipation-related, PD-related and QOL-related questionnaires at visits 2 and 4 (week 4). Subjective symptoms and objective findings will be collected at visits 2, 3 (week 2) and 4. Since patients' motor function might be improved by treatment of constipation, the use of dopamine preparations will also be monitored. Bowel movement data and other parameters will be compared between groups.Safety information will be collected as adverse events, specifically focusing on those occurring in association with study conduct. ETHICS AND DISSEMINATION: This study will be conducted in accordance with the Helsinki Declaration, the Clinical Trials Act of the Japan Ministry of Health, Labour and Welfare, and related laws and regulations. The study was approved by the Juntendo University Certified Review Board. The results will be disseminated through an online study registry (Japan Registry of Clinical Trials), presented at scientific conferences, and published in medical journals. TRIAL REGISTRATION NUMBER: JPRN-jRCTs031200172; Pre-results.
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Enfermedad de Parkinson , Calidad de Vida , Proteínas Portadoras , Estreñimiento/tratamiento farmacológico , Estreñimiento/etiología , Dipéptidos , Método Doble Ciego , Humanos , Glicoproteínas de Membrana , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/tratamiento farmacológico , Tiazepinas , Resultado del TratamientoRESUMEN
BACKGROUNDS: Although the short-term efficacy of bilateral subthalamic deep brain stimulation (DBS) has been reported in a limited number of Parkinson's disease (PD) patients with SNCA mutations, there are no data for long-term outcome. METHODS: This multicenter retrospective study investigated previously reported PD patients with SNCA mutations, implanted with bilateral subthalamic DBS. We compared demographic and clinical data at baseline and last follow-up. Clinical data of motor and nonmotor symptoms and motor fluctuation were collected up to 10 years from DBS surgery. RESULTS: Among four subjects, three had SNCA duplication and one had c.158C.A (p.A53E) mutation. The mean post-implantation follow-up duration was 5.4 ± 3.7 years. All patients with SNCA duplication showed favorable outcome, although one died from breast cancer 1.5 years after DBS. The patient with the missense mutation became wheelchair-bound due to progressed axial, cognitive and psychiatric symptoms after 3.5 years from DBS despite the benefit on motor fluctuation. CONCLUSION: Based on findings in our small cohort, subthalamic DBS could be beneficial for motor fluctuation in PD patients with SNCA mutations, especially those with SNCA duplication, and cognitive and psychiatric symptoms are important for the long-term outcome of subthalamic DBS.
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Estimulación Encefálica Profunda , Enfermedad de Parkinson , Núcleo Subtalámico , Estudios de Seguimiento , Humanos , Mutación , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/psicología , Enfermedad de Parkinson/terapia , Estudios Retrospectivos , Resultado del Tratamiento , alfa-Sinucleína/genéticaRESUMEN
Multiple system atrophy (MSA) is classified into two main types: parkinsonian and cerebellar ataxia with oligodendrogliopathy. We examined microstructural alterations in the white matter and the substantia nigra pars compacta (SNc) of patients with MSA of parkinsonian type (MSA-P) using multishell diffusion magnetic resonance imaging (dMRI) and myelin sensitive imaging techniques. Age- and sex-matched patients with MSA-P (n = 21, n = 10 first and second cohorts, respectively), Parkinson's disease patients (n = 19, 17), and healthy controls (n = 20, 24) were enrolled. Magnetization transfer saturation imaging (MT-sat) and dMRI were obtained using 3-T MRI. Measurements obtained from diffusion tensor imaging (DTI), free-water elimination DTI, neurite orientation dispersion and density imaging (NODDI), and MT-sat were compared between groups. Tract-based spatial statistics analysis revealed differences in diffuse white matter alterations in the free-water fractional volume, myelin volume fraction, and intracellular volume fraction between the patients with MSA-P and healthy controls, whereas free-water and MT-sat differences were limited to the middle cerebellar peduncle in comparison with those with Parkinson's disease. Region-of-interest analysis of white matter and SNc revealed significant differences in the middle and inferior cerebellar peduncle, pontine crossing tract, corticospinal tract, and SNc between the MSA-P and healthy controls and/or Parkinson's disease patients. Our results shed light on alterations to brain microstructure in MSA.
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We describe the case of a 51-year-old man with Parkinson's disease (PD) presenting with motor fluctuations, who received bilateral subthalamic deep brain stimulation (DBS) with an adaptive DBS (aDBS) device, Percept™ PC (Medtronic, Inc. , Minneapolis, MN). This device can deliver electrical stimulations based on fluctuations of neural oscillations of the local field potential (LFP) at the target structure. We observed that the LFP fluctuations were less evident inside the hospital than outside, while the stimulation successfully adapted to beta oscillation fluctuations during the aDBS phase without any stimulation-induced side effects. Thus, this new device facilitates condition-dependent stimulation; this new stimulation method is feasible and provides new insights into the pathophysiological mechanisms of PD.
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INTRODUCTION: The non-motor symptoms (NMSs) of Parkinson's disease (PD) significantly impact the patient's health-related quality of life. This subanalysis of the J-FIRST study evaluated the effect of istradefylline, a selective adenosine A2A receptor antagonist, on NMSs in istradefylline-naïve Japanese patients with PD. METHODS: Patients with PD and ≥1 NMS and 'wearing-off' with their current antiparkinsonian treatment were observed for up to 52 weeks. The effect of istradefylline on NMSs was measured in terms of changes in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part 1 total, individual sub-items scores and the 8 item PD questionnaire (PDQ-8) estimated by the marginal structural model. RESULTS: Overall, 732 patients were istradefylline-naïve prior to the study, of whom 171 were treated with istradefylline for ≥8 weeks during the observation period (istradefylline-treated patients). At baseline, istradefylline-treated patients were more likely to have a dyskinesia (49.7% vs 40.8%) and received a significantly higher daily dose of levodopa (462.8 mg vs 413.0 mg) than those who did not receive istradefylline (n = 561). MDS-UPDRS Part 1 total score at the end of the 52-week observational period slightly increased in patients who received istradefylline and those who did not (0.49 ± 0.41 vs 0.07 ± 0.20; P = 0.36). There were no statistically significant differences between the two groups of patients in terms of changes in the MDS-UPDRS Part 1 total score or any sub-items, or in the PDQ-8 total score. CONCLUSION: NMSs remained generally controlled in istradefylline-treated Japanese patients with PD who exhibited wearing-off with their current antiparkinsonian treatment. Istradefylline could be a feasible treatment option for patients with advanced PD, without worsening existing NMSs.
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Antiparkinsonianos/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Purinas/uso terapéutico , Calidad de Vida , Anciano , Discinesias/tratamiento farmacológico , Discinesias/etiología , Femenino , Humanos , Japón , Levodopa/uso terapéutico , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/psicología , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
INTRODUCTION: Levodopa-induced dyskinesia is a complication of levodopa therapy and negatively impacts the quality of life of patients. We aimed to elucidate white matter alterations in Parkinson's disease with levodopa-induced dyskinesia using advanced diffusion magnetic resonance imaging techniques. METHODS: The enrolled subjects included 26 clinically confirmed Parkinson's disease patients without levodopa-induced dyskinesia, 25 Parkinson's disease patients with levodopa-induced dyskinesia, and 23 healthy controls. Subjects were imaged using a 3-T magnetic resonance scanner. Diffusion tensor imaging, diffusion kurtosis imaging, and neurite orientation dispersion and density imaging findings were compared between groups with a group-wise whole brain approach and a region-of-interest analysis for each white matter tract. Additionally, logistic regression analysis was used to calculate odds ratios for levodopa-induced dyskinesia. RESULTS: Group-wise tract-based spatial statistical analysis revealed significant white matter differences in isotropic diffusion, complexity, or heterogeneity, and neurite density between healthy controls and Parkinson's disease patients without levodopa-induced dyskinesia and between patients with and without levodopa-induced dyskinesia. Region-of-interest analysis revealed similar alterations using a group-wise whole-brain approach in the external capsule, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, and uncinate fasciculus. These tracts had an odds ratio of approximately 2.3 for the presence of levodopa-induced dyskinesia. CONCLUSIONS: Our findings suggest that Parkinson's disease with levodopa-induced dyskinesia produces less white matter microstructural disruption, especially in temporal lobe fibers, than Parkinson's disease without levodopa-induced dyskinesia. These fibers has a more than 2-fold odds ratio for the presence of levodopa-induced dyskinesia and might be associated with the pathogenesis of the sequela.
Asunto(s)
Antiparkinsonianos/efectos adversos , Discinesia Inducida por Medicamentos/patología , Levodopa/efectos adversos , Enfermedad de Parkinson/tratamiento farmacológico , Sustancia Blanca/patología , Anciano , Biomarcadores/análisis , Estudios de Casos y Controles , Imagen de Difusión por Resonancia Magnética , Discinesia Inducida por Medicamentos/etiología , Femenino , Humanos , Masculino , Fibras Nerviosas/patología , Oportunidad Relativa , Lóbulo Temporal/patología , Sustancia Blanca/ultraestructuraRESUMEN
OBJECTIVE: To evaluate whether orthostatic hypotension (OH) or supine hypertension (SH) is associated with brain atrophy and white matter hyperintensities (WMH), we analyzed clinical and radiologic data from a large multicenter consortium of patients with Parkinson disease (PD) and dementia with Lewy bodies (DLB). METHODS: Supine and orthostatic blood pressure (BP) and structural MRI data were extracted from patients with PD and DLB evaluated at 8 tertiary-referral centers in the United States, Canada, Italy, and Japan. OH was defined as a systolic/diastolic BP fall ≥20/10 mm Hg within 3 minutes of standing from the supine position (severe ≥30/15 mm Hg) and SH as a BP ≥140/90 mm Hg with normal sitting BP. Diagnosis-, age-, sex-, and disease duration-adjusted differences in global and regional cerebral atrophy and WMH were appraised with validated semiquantitative rating scales. RESULTS: A total of 384 patients (310 with PD, 74 with DLB) met eligibility criteria, of whom 44.3% (n = 170) had OH, including 24.7% (n = 42) with severe OH and 41.7% (n = 71) with SH. OH was associated with global brain atrophy (p = 0.004) and regional atrophy involving the anterior-temporal (p = 0.001) and mediotemporal (p = 0.001) regions, greater in severe vs nonsevere OH (p = 0.001). The WMH burden was similar in those with and without OH (p = 0.49). SH was not associated with brain atrophy (p = 0.59) or WMH (p = 0.72). CONCLUSIONS: OH, but not SH, was associated with cerebral atrophy in Lewy body disorders, with prominent temporal region involvement. Neither OH nor SH was associated with WMH.