ABSTRACT
Abnormal deposition of α-synuclein is a key feature and biomarker of Parkinson's disease. α-Synuclein aggregates can propagate themselves by a prion-like seeding-based mechanism within and between tissues and are hypothesized to move between the intestine and brain. α-Synuclein RT-QuIC seed amplification assays have detected Parkinson's-associated α-synuclein in multiple biospecimens including post-mortem colon samples. Here we show intra vitam detection of seeds in duodenum biopsies from 22/23 Parkinson's patients, but not in 6 healthy controls by RT-QuICR. In contrast, no tau seeding activity was detected in any of the biopsies. Our seed amplifications provide evidence that the upper intestine contains a form(s) of α-synuclein with self-propagating activity. The diagnostic sensitivity and specificity for PD in this biopsy panel were 95.7% and 100% respectively. End-point dilution analysis indicated up to 106 SD50 seeding units per mg of tissue with positivity in two contemporaneous biopsies from individual patients suggesting widespread distribution within the superior and descending parts of duodenum. Our detection of α-synuclein seeding activity in duodenum biopsies of Parkinson's disease patients suggests not only that such analyses may be useful in ante-mortem diagnosis, but also that the duodenum may be a source or a destination for pathological, self-propagating α-synuclein assemblies.
Subject(s)
Parkinson Disease , Humans , Parkinson Disease/diagnosis , alpha-Synuclein , Biopsy , Intestines , DuodenumABSTRACT
BACKGROUND: Several earlier studies showed a female predominance in idiopathic adult-onset dystonia (IAOD) affecting the craniocervical area and a male preponderance in limb dystonia. However, sex-related differences may result from bias inherent to study design. Moreover, information is lacking on whether sex-related differences exist in expressing other dystonia-associated features and dystonia spread. OBJECTIVE: To provide accurate information on the relationship between sex differences, motor phenomenology, dystonia-associated features and the natural history of IAOD. METHODS: Data of 1701 patients with IAOD from the Italian Dystonia Registry were analysed. RESULTS: Women predominated over men in blepharospasm, oromandibular, laryngeal and cervical dystonia; the sex ratio was reversed in task-specific upper limb dystonia; and no clear sex difference emerged in non-task-specific upper limb dystonia and lower limb dystonia. This pattern was present at disease onset and the last examination. Women and men did not significantly differ for several dystonia-associated features and tendency to spread. In women and men, the absolute number of individuals who developed dystonia tended to increase from 20 to 60 years and then declined. However, when we stratified by site of dystonia onset, different patterns of female-to-male ratio over time could be observed in the various forms of dystonia. CONCLUSIONS: Our findings provide novel evidence on sex as a key mediator of IAOD phenotype at disease onset. Age-related sexual dimorphism may result from the varying exposures to specific age-related and sex-related environmental risk factors interacting in a complex manner with biological factors such as hormonal sex factors.
Subject(s)
Age of Onset , Dystonic Disorders , Humans , Male , Female , Middle Aged , Adult , Dystonic Disorders/physiopathology , Aged , Sex Factors , Registries , Italy , Young Adult , Dystonia/physiopathology , Blepharospasm/physiopathology , Disease ProgressionABSTRACT
A few earlier observations and recent controlled studies pointed to the possible contribution of thyroid diseases in idiopathic adult-onset dystonia (IAOD). The aim of this study was to investigate the association between thyroid status and clinical characteristics of IAOD, focusing on dystonia localization, spread, and associated features such as tremors and sensory tricks. Patients were identified from those included in the Italian Dystonia Registry, a multicentre dataset of patients with adult-onset dystonia. The study population included 1518 IAOD patients. Patients with hypothyroidism and hyperthyroidism were compared with those without any thyroid disease. In the 1518 IAOD patients, 167 patients (11%; 95% CI 9.5-12.6%) were diagnosed with hypothyroidism and 42 (2.8%; 95% CI 1.99-3.74) with hyperthyroidism. The three groups were comparable in age at dystonia onset, but there were more women than men in the groups with thyroid disease. Analysing the anatomical distribution of dystonia, more patients with blepharospasm were present in the hyperthyroidism group, but the difference did not reach statistical significance after the Bonferroni correction. The remaining dystonia-affected body sites were similarly distributed in the three groups, as did dystonia-associated features and spread. Our findings provided novel information indicating that the high rate of thyroid diseases is not specific for any specific dystonia subpopulation and does not appear to influence the natural history of the disease.
Subject(s)
Dystonia , Dystonic Disorders , Hyperthyroidism , Hypothyroidism , Thyroid Diseases , Male , Adult , Humans , Female , Dystonia/epidemiology , Risk Factors , Dystonic Disorders/epidemiology , Hypothyroidism/epidemiology , Hyperthyroidism/complications , Hyperthyroidism/epidemiology , Registries , Italy/epidemiologyABSTRACT
OBJECTIVE: The aim of the present study was to assess emergency neurology management in Italy by comparing patients admitted to the hub and spoke hospitals. METHODS: Data obtained from the annual Italian national survey (NEUDay) investigating the activity and facilities of neurology in the emergency room conducted in November 2021 were considered. Information for each patient who received a neurologic consultation after accessing the emergency room was acquired. Data on facilities were also gathered, including hospital classification (hub vs spoke), number of consultations, presence of neurology and stroke unit, number of beds, availability of neurologist, radiologist, neuroradiologist, and instrumental diagnostic accessibility. RESULTS: Overall, 1,111 patients were admitted to the emergency room and had neurological consultation across 153 facilities (out of the 260 Italian ones). Hub hospitals had significantly more beds, availability of neurological staff, and instrumental diagnostic accessibility. Patients admitted to hub hospital had a greater need for assistance (higher number of yellow/red codes at neurologist triage). A higher propensity to be admitted to hub centers for cerebrovascular problems and to receive a diagnosis of stroke was observed. CONCLUSIONS: The identification of hub and spoke hospitals is strongly characterized by the presence of beds and instrumentation mainly dedicated to acute cerebrovascular pathologies. Moreover, the similarity in the number and type of accesses between hub and spoke hospitals suggests the need to look for adequate identification of all the neurological pathologies requiring urgent treatment.
ABSTRACT
I n the context of an adequate health care organization, the figure of the neurologist as an emergency operator (in the emergency room-ER-and/or in a dedicated outpatient clinic) is crucial for an effective functional connection with the territory (and therefore with general practitioners), a reduction in inappropriate ER accesses, specific diagnostic and therapeutic approaches to neurological emergencies in the ER and a reduction in nonspecific or even unnecessary instrumental investigations. In this position paper of the Italian Association of Emergency Neurology (ANEU: Associazione Neurologia dell'Emergenza Urgenza), these issues are addressed, and two important organizational solutions are proposed: 1) The Neuro Fast Track, as an outpatient organization approach strongly linked to general practitioners and non-neurological specialists and dedicated to cases with deferrable urgency (to be assessed within 72 h) 2) The identification of an emergency neurologist, who is engaged in ER assessments as a consultant and involved in the management of the semi-intensive care unit of the emergency neurology and the stroke unit according to an appropriate rotation, as well as in consultations for patients with neurological emergencies in inpatient wards The possibility of computerizing the screening of patients with deferrable urgency in the Neuro Fast Track is described. A dedicated app represents an important tool that can facilitate the identification of patients for whom deferred assessment is appropriate, the scheduling of neurological examinations and reductions in the booking time through a more rapid approach to specialist assessment and subsequent investigations.
Subject(s)
Neurologists , Neurology , Humans , Emergencies , Emergency Service, Hospital , ItalyABSTRACT
BACKGROUND: Frequency of Advanced Parkinson's Disease (APD) and its clinical characteristics are still not well defined. Here, we aimed to assess APD prevalence in the Italian OBSERVE-PD cohort, as well as treatment eligibility to device-aided therapies (DAT), and to compare the APD clinical judgment with the established Delphi criteria. METHODS: This sub-group analysis of the OBSERVE-PD study was performed on patients enrolled by 9 Movement Disorders centers in Italy. Motor and non-motor symptoms, PD characteristics, activities of daily living, and quality of life were assessed. Patient eligibility for DAT, response to current PD treatments, referral process, and the concordance between APD physician's judgment and Delphi criteria were also assessed. RESULTS: According to physician's judgment, 60 out of 140 patients (43%) had APD. The correlation between physician's judgment and the overall APD Delphi criteria was substantial (K = 0.743; 95%CI 0.633-0.853), mainly driven by a discrete concordance found for the presence of ≥ 2 h of daily OFF time, presence of troublesome dyskinesia, ≥ 5 times daily oral levodopa dosing, and activities of daily living limitation. Forty-four (73%) APD patients were considered eligible to DAT but only 18 of them (41%) used these therapies, while most patients, independently from their eligibility, continued to use 3-5 oral daily medications, due to fear of invasive solutions and need to have a longer time to decide. CONCLUSION: APD was frequent in the Italian OBSERVE-PD population. DAT in the eligible APD population proved to be underused, in spite of unsatisfactory symptoms control with oral medications in 67% of patients.
Subject(s)
Activities of Daily Living , Parkinson Disease , Antiparkinson Agents/therapeutic use , Humans , Italy/epidemiology , Parkinson Disease/diagnosis , Parkinson Disease/drug therapy , Parkinson Disease/epidemiology , Quality of LifeABSTRACT
BACKGROUND: Freezing of gait (FOG) is a disabling motor symptom occurring mainly in the advanced stage of Parkinson's disease (PD). METHODS: This review outlines the clinical manifestation of FOG and its relationship with levodopa treatment, the differential diagnosis with respect to other neurodegenerative and secondary forms and the available treatment. RESULTS: We report the proposed models explaining the FOG phenomenon and summarize the available knowledge on FOG etiology's potential genetic contribution. A complete understanding of the mechanisms underlying FOG in PD is essential to find the best therapy. Different treatment options exist but are still not entirely successful, and often a combination of approaches is needed. CONCLUSIONS: Further studies focusing on the potential genetic role in FOG may increase the knowledge on the FOG etiology and pathophysiology, allowing further individualized treatment strategies for this very disabling phenomenon.
Subject(s)
Gait Disorders, Neurologic , Parkinson Disease , Causality , Gait , Gait Disorders, Neurologic/drug therapy , Gait Disorders, Neurologic/therapy , Humans , Levodopa/therapeutic use , Parkinson Disease/complications , Parkinson Disease/diagnosis , Parkinson Disease/geneticsABSTRACT
BACKGROUND AND PURPOSE: Despite enormous advances in identifying genetic variants responsible for many neurological diseases, access to genetic testing may be limited in clinical practice. The objective of this study was to assess worldwide access to genetic tests for movement disorders and factors impacting their utilization. METHODS: The Rare Movement Disorders Study Group of the International Parkinson and Movement Disorder Society designed an online survey electronically mailed to all 7815 members. RESULTS: Survey data completed by 1269 participants from 109 countries were analysed. Limited access to geneticists and genetic counsellors was reported in many world regions compared to Europe and North America. Availability of genetic testing was limited, with rates of access lower than 50%. Genetic testing for chorea was the most commonly available. For parkinsonism, dystonia, ataxia, hereditary spastic paraplegias and metabolic disorders, there was limited access to genetic testing in all countries compared to Europe and North America, with significant differences found for Africa, Central/South America, Asia. In many regions, genetic testing was supported by either private or public funding. Genetic testing was free of charge in Europe according to 63.5% of respondents. In North America, Africa, Central/South America, Asia and the Middle East access to free of charge genetic testing was by far significantly lower compared to Europe. CONCLUSIONS: This survey highlights difficulties in accessing genetic testing and individuals with expertise in genetics at the worldwide level. In addition, major disparities in genetic testing amongst world regions are highlighted, probably due to a variety of factors including financial barriers.
Subject(s)
Movement Disorders , Asia , Europe , Genetic Testing , Humans , Middle East , Movement Disorders/geneticsABSTRACT
BACKGROUND AND PURPOSE: Recent data suggest that imbalances in the composition of the gut microbiota (GM) could exacerbate the progression of Parkinson disease (PD). The effects of levodopa (LD) have been poorly assessed, and those of LD-carbidopa intestinal gel (LCIG) have not been evaluated so far. The aim of this study was to identify the effect of LD and LCIG, in particular, on the GM and metabolome. METHODS: Fecal DNA samples from 107 patients with a clinical diagnosis of PD were analyzed by next-generation sequencing of the V3 and V4 regions of the 16S rRNA gene. PD patients were classified in different groups: patients on LCIG (LCIG group, n = 38) and on LD (LD group, n = 46). We also included a group of patients (n = 23) without antiparkinsonian medicaments (Naïve group). Fecal metabolic extracts were evaluated by gas chromatography mass spectrometry. RESULTS: The multivariate analysis showed a significantly higher abundance in the LCIG group of Enterobacteriaceae, Escherichia, and Serratia compared to the LD group. Compared to the Naïve group, the univariate analysis showed a reduction of Blautia and Lachnospirae in the LD group. Moreover, an increase of Proteobacteria, Enterobacteriaceae, and a reduction of Firmicutes, Lachnospiraceae, and Blautia was found in the LCIG group. No significant difference was found in the multivariate analysis of these comparisons. The LD group and LCIG group were associated with a metabolic profile linked to gut inflammation. CONCLUSIONS: Our results suggest that LD, and mostly LCIG, might significantly influence the microbiota composition and host/bacteria metabolism, acting as stressors in precipitating a specific inflammatory intestinal microenvironment, potentially related to the PD state and progression.
Subject(s)
Gastrointestinal Microbiome , Parkinson Disease , Antiparkinson Agents , Carbidopa , Drug Combinations , Gels , Humans , Levodopa , Metabolome , Parkinson Disease/drug therapy , RNA, Ribosomal, 16S/geneticsABSTRACT
In genetic prion diseases (gPrD), five genetic variants (E200K, V210I, V180I, P102L, and D178N) are responsible for about 85% of cases. The R208H is one of the several additional rare mutations and to date, only 16 cases carrying this mutation have been reported worldwide. To describe the phenotypic features of 5 affected patients belonging to apparently unrelated Sardinian (Italian) families with R208H gPrD, and provide evidence for a possible founder effect are the aims of this study. The R208H PRNP mutation has a much higher relative frequency in Sardinia than elsewhere in Italy (72% vs. 4.4% of gCJD cases). Our cohort shared similar phenotypic features to the previously described patients with R208H-129M haplotype with most patients showing the classical Creutzfeldt-Jakob disease (CJD) phenotype. The analysis of 10 controls and 5 patients by NGS sequencing identified 4 haplotypes, 3 associated with the wild type variant, and one (H1) shared by all patients carrying the 208His variant. This is the first report of a regional cluster for R208H mutation in gPrD and the first report of the presence of a common ancestor for this Sardinian R208H cluster, confirming the probable consequences of genetic isolation process even for rare diseases.
Subject(s)
Creutzfeldt-Jakob Syndrome/genetics , Founder Effect , Mutation , Prion Proteins/genetics , Aged , Alleles , Cluster Analysis , Family Health , Female , Haplotypes , High-Throughput Nucleotide Sequencing , Humans , Italy/epidemiology , Male , Middle Aged , PhenotypeABSTRACT
BACKGROUND: Variants in GBA are the most common genetic risk factor for Parkinson's disease (PD). The impact of different variants on the PD clinical spectrum is still unclear. OBJECTIVES: We determined the frequency of GBA-related PD in Italy and correlated GBA variants with motor and nonmotor features and their occurrence over time. METHODS: Sanger sequencing of the whole GBA gene was performed. Variants were classified as mild, severe, complex, and risk. ß-glucocerebrosidase activity was measured. The Kaplan-Meier method and Cox proportional hazard regression models were performed. RESULTS: Among 874 patients with PD, 36 variants were detected in 14.3%, including 20.4% early onset. Patients with GBA-PD had earlier and more frequent occurrence of several nonmotor symptoms. Patients with severe and complex GBA-PD had the highest burden of symptoms and a higher risk of hallucinations and cognitive impairment. Complex GBA-PD had the lowest ß-glucocerebrosidase activity. CONCLUSIONS: GBA-PD is highly prevalent in Italy. Different types of mutations underlie distinct phenotypic profiles. © 2020 International Parkinson and Movement Disorder Society.
Subject(s)
Parkinson Disease , Dissection , Genotype , Glucosylceramidase/genetics , Humans , Italy/epidemiology , Mutation/genetics , Parkinson Disease/epidemiology , Parkinson Disease/genetics , PhenotypeABSTRACT
The TANDEM investigation was carried out in 17 Italian Movement Disorder centers on behalf of a joint initiative of neurologist members of the Italian Academy for Parkinson's disease and Movement Disorders (LIMPE-DISMOV Academy) and gastroenterologist members of the Italian Society of Digestive Endoscopy (SIED) to evaluate the efficacy and tolerability of levodopa-carbidopa intestinal gel (LCIG) in patients with advanced Parkinson's disease (PD) in routine medical care. Motor scores in "ON" and OFF" state (UPDRS-III), complications of therapy (UPDRS-IV), activities of daily living, sleep disorders and quality of life were evaluated at baseline and at two follow-up assessments (FUV1 and FUV2) within the initial 12-month LCIG treatment. In 159 patients (55% males) with a mean age of 69.1 ± 6.6 years and a diagnosis of PD since 13.6 ± 5.5 years, the UPDRS-III total score (in "OFF") decreased from baseline (45.8 ± 13.2) to FUV1 (41.0 ± 17.4; p < 0.001) and FUV2 (40.5 ± 15.5; p < 0.001), the UPDRS-IV total score decreased from baseline (8.8 ± 2.9) to FUV1 (5.1 ± 3.4; p < 0.001) and FUV2 (5.5 ± 3.2; p < 0.001). The percentage of patients exhibiting freezing, dystonia, gait/walking disturbances, falls, pain and sleep disorders was significantly reduced. Twenty-eight device complications were reported and 11 (6.9%) patients prematurely terminated the study. LCIG after 12-month treatment led to sustained improvement of time spent in "OFF", complications of therapy, PD-associated symptoms and sleep disorders. LCIG tolerability was consistent with the established safety profile of LCIG.
Subject(s)
Carbidopa , Parkinson Disease , Activities of Daily Living , Antiparkinson Agents/adverse effects , Carbidopa/adverse effects , Drug Combinations , Female , Gels , Humans , Infant, Newborn , Levodopa/adverse effects , Male , Parkinson Disease/drug therapy , Quality of LifeABSTRACT
Cervical dystonia is associated with neck pain in a significant proportion of cases, but the mechanisms underlying pain are largely unknown. In this exploratory study, we compared demographic and clinical variables in cervical dystonia patients with and without neck pain from the Italian Dystonia Registry. Univariable and multivariable logistic regression analysis indicated a higher frequency of sensory trick and a lower educational level among patients with pain.
Subject(s)
Dystonic Disorders , Torticollis , Demography , Humans , Neck Pain/epidemiology , Torticollis/complications , Torticollis/epidemiologyABSTRACT
Deficits in olfaction are among the most frequent non-motor symptoms in Parkinson's disease (PD) and can be detected early compared with motor symptoms. The reason for the early onset, as well as the mechanism involved remains unknown. We aimed to characterize the olfactory performance of patients with PD and age-matched healthy control (HC) participants in association with gender and a specific polymorphism in the odorant-binding protein IIa (OBPIIa) gene, which plays a crucial role in the perception of odors. The olfactory performance was assessed using the odor identification part of the Sniffin' Sticks test in 249 participants (patients with PD: n = 131 and HC participants: n = 118). All participants were genotyped for the rs2590498 polymorphism of the OBPIIa gene, whose major allele A is associated with a higher retronasal perception than the minor allele G. A higher number of men with PD than women with PD exhibited hyposmia. Importantly, OBPIIa gene polymorphism showed an effect on PD-related olfactory deficits only in women. Women with PD carrying two sensitive alleles (AA) showed a better olfactory performance than women with PD with at least one insensitive allele (G); the olfactory scores of the AA genotype women with PD were not different from those of HC participants. In conclusion, our results confirmed a sex effect on the reduced olfactory performance of patients with PD and identified the OBPIIa locus, which may provide a mechanism to determine the risk factor for olfactory deficits in women with PD at the molecular level.
Subject(s)
Lipocalins/genetics , Olfactory Perception/genetics , Parkinson Disease/genetics , Aged , Alleles , Computational Biology , Female , Genetic Variation/genetics , Humans , Lipocalins/metabolism , Male , Olfaction Disorders/genetics , Olfaction Disorders/metabolism , Polymorphism, Single Nucleotide/genetics , Sex FactorsABSTRACT
BACKGROUND: Intracranial hypotension has been associated with a wide spectrum of neurological conditions including chronic non-aneurysmal and acute aneurysmal subarachnoid hemorrhage. CASE: A 59-year-old man presented with a non-aneurysmal subarachnoid hemorrhage in a perimesencephalic pattern after a mild physical exertion. In the course of the disease, a magnetic resonance imaging of head and spine displayed intracranial hypotension that resolved spontaneously. DISCUSSION: Long-standing intracranial hypotension has been reported as the cause of chronic subarachnoid hemorrhage and a single case of intracranial hypotension as the consequence of intracranial pressure fluctuations after acute aneurysmal subarachnoid hemorrhage has been described. This is the first description of intracranial hypotension caused by acute non-aneurysmal subarachnoid hemorrhage. We hypothesize that blood in the subarachnoid space could have determined a spine cerebrospinal fluid leak through intracranial pressure fluctuations or mechanical action, causing arachnoiditis and possibly a dural tear.
Subject(s)
Intracranial Hypotension/etiology , Subarachnoid Hemorrhage/complications , Headache/etiology , Humans , Male , Middle AgedABSTRACT
BACKGROUND: Superficial siderosis (SS) of the central nervous system is a rare and heterogeneous condition due to deposition of hemosiderin on the surface of the brain and spinal cord. The usually progressive clinical course is characterized by a combination of hearing loss, cerebellar ataxia, and myelopathy. There is no known treatment for SS, but the iron chelator deferiprone (DFP) has been proposed as a potentially useful treatment. METHODS: We present a long-term (average 3.7 years) evaluation of four cases of SS treated with DFP (15 mg/kg po bid). RESULTS: Treatment with DFP proved safe and well tolerated. Two out of the four subjects were unchanged while the other two presented a clinical improvement with reduction of postural instability and cerebellar signs. Blinded evaluation of magnetic resonance imaging (performed every 6 months during follow-up) showed a reduction of the abnormal iron deposition for all patients. CONCLUSIONS: This long-term observational study suggests that DFP may be effective in the management of the neurological manifestations associated with iron accumulation in SS. CLINICALTRIALS. GOV IDENTIFIER: NTC00907283.
Subject(s)
Central Nervous System Diseases/drug therapy , Deferiprone/therapeutic use , Iron Chelating Agents/therapeutic use , Aged , Brain/diagnostic imaging , Central Nervous System Diseases/diagnostic imaging , Deferiprone/adverse effects , Follow-Up Studies , Hemosiderin , Humans , Iron Chelating Agents/adverse effects , Male , Middle Aged , Single-Blind Method , Spinal Cord/diagnostic imaging , Treatment OutcomeABSTRACT
OBJECTIVE: This study aimed to quantitatively investigate the existence of differences in spatiotemporal and kinematic parameters of gait in men and women with Parkinson disease (PD) using computerized 3-dimensional gait analysis. DESIGN: Retrospective cohort study. SETTING: Laboratory of Biomechanics. PARTICIPANTS: Individuals with PD (N=35; 17 female, 18 male) of mean age 70.7 years characterized by mild disability (Hoehn and Yahr ≤2.5) who were tested in On medication state approximately 60 to 90 minutes after intake of the usual morning Levodopa dose. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Spatiotemporal parameters of gait (speed, stride length, cadence, step width, duration of stance, swing, double support phases) and kinematics of hip, knee, and ankle joints in the sagittal plane. RESULTS: Men and women exhibit similar spatiotemporal parameters, except for step width (wider in men). In contrast, relevant differences were found in terms of ankle kinematics. In particular, women presented increased ankle dorsiflexion through all the stance phase and mid to late swing phase, and reduced plantarflexion at the stance-swing phase transition. CONCLUSIONS: Gait patterns of men and women with PD with mild disability are similar in terms of spatiotemporal parameters but characterized by marked differences regarding the ankle kinematics on the sagittal plane. The findings of the present study support the concept that investigations seeking to clarify the complex pathophysiology of PD-related gait disturbances should consider the role played by an individual's sex, thereby achieving more effective designing of physical and rehabilitative treatments.
Subject(s)
Gait/physiology , Lower Extremity/physiopathology , Parkinson Disease/physiopathology , Aged , Aged, 80 and over , Biomechanical Phenomena , Female , Humans , Italy , Male , Middle Aged , Mobility Limitation , Range of Motion, Articular/physiology , Retrospective Studies , Severity of Illness Index , Sex Factors , Walking/physiology , Walking SpeedABSTRACT
BACKGROUND: The few studies that evaluated taste function in Parkinson's disease (PD) showed inconsistent results. The inherited ability to taste the bitter compound of 6-n-propylthiouracil has been considered to be a paradigm of general taste perception. 6-n-propylthiouracil taste perception is mediated by the TAS2R38 receptor, and reduced 6-n-propylthiouracil sensitivity has been associated with several diseases not typically related to taste function. OBJECTIVES: We evaluated the 6-n-propylthiouracil taste perception and the TAS2R38 gene as genetic risk factors for the development of idiopathic PD in PD patients and healthy controls (HC). METHODS: The 6-n-propylthiouracil taste perception was assessed by testing the responsiveness, and the ability to recognize, 6-n-propylthiouracil and sodium chloride. The participants were classified for 6-n-propylthiouracil taster status and genotyped for the TAS2R38 gene. RESULTS: A significant increase in the frequency of participants classified as 6-n-propylthiouracil nontasters and a reduced ability to recognize bitter taste quality of 6-n-propylthiouracil were found in PD patients when compared with healthy controls. The results also showed that only 5% of PD patients had the homozygous genotype for the dominant tasting variant of TAS2R38, whereas most of them carried the recessive nontaster form and a high number had a rare variant. CONCLUSIONS: Our results show that 6-n-propylthiouracil taster status and TAS2R38 locus are associated with PD. The 6-n-propylthiouracil test may therefore represent a novel, simple way to identify increased vulnerability to PD. Moreover, the presence of the nontasting form of TAS2R38 in PD may further substantiate that disease-associated taste disruption may represent a risk factor associated with the disease. © 2018 International Parkinson and Movement Disorder Society.
Subject(s)
Parkinson Disease/complications , Polymorphism, Single Nucleotide/genetics , Receptors, G-Protein-Coupled/genetics , Taste Disorders/etiology , Taste Disorders/genetics , Taste Perception/genetics , Aged , Antimetabolites/administration & dosage , Case-Control Studies , Female , Genotype , Humans , Male , Middle Aged , Parkinson Disease/genetics , Propylthiouracil/administration & dosage , Severity of Illness Index , Statistics, Nonparametric , Taste/genetics , Taste Perception/drug effectsABSTRACT
After 25 years of deep brain stimulation (DBS) for the treatment of Parkinson's disease, it has become increasingly recognized that a range of postoperative urgent situations and emergencies may occur. In this review we describe the possible scenarios of DBS-related emergencies: perioperative (intraoperative and early postoperative) and postoperative settings and issues from suboptimal control of motor and nonmotor symptoms in the early programming phase and during long-term follow-up. We also outline potential advantages in the management of these emergencies offered by the newest devices, emerging technologies, and new possibilities in programming.