Posterior insula repetitive transcranial magnetic stimulation for chronic pain in patients with Parkinson disease - pain type matters: A double-blinded randomized sham-controlled trial.

OBJECTIVES: Altered somatosensory processing in the posterior insula may play a role in chronic pain development and contribute to Parkinson disease (PD)-related pain. Posterior-superior insula (PSI) repetitive transcranial magnetic stimulation (rTMS) has been demonstrated to have analgesic effects among patients with some chronic pain conditions. This study aimed at assessing the efficacy of PSI-rTMS for treating PD-related pain. METHODS: This was a double-blinded, randomized, sham-controlled, parallel-arm trial (NCT03504748). People with PD (PwP)-related chronic pain underwent five daily PSI-rTMS sessions for a week, followed by once weekly maintenance stimulations for seven weeks. rTMS was delivered at 10 Hz and 80% of the resting motor threshold. The primary outcome was a ≥ 30% pain intensity reduction at 8 weeks compared to baseline. Functionality, mood, cognitive, motor status, and somatosensory thresholds were also assessed. RESULTS: Twenty-five patients were enrolled. Mean age was 55.2 ± 9.5 years-old, and 56% were female. Nociceptive pain accounted for 60%, and neuropathic and nociplastic for 20% each. No significant difference was found for 30% pain reduction response rates between active (42.7%) and sham groups (14.6%, p = 0.26). Secondary clinical outcomes and sensory thresholds also did not differ significantly. In a post hoc analysis, PwP with nociceptive pain sub-type experienced more pain relief after active (85.7%) compared to sham PSI-rTMS (25%, p = 0.032). CONCLUSION: Our preliminary results suggest that different types of PD-related pain may respond differently to treatment, and therefore people with PD may benefit from having PD-related pain well characterized in research trials and in clinical practice.

Botulinum Toxin and Deep Brain Stimulation in Dystonia.

Deep Brain Stimulation (DBS) is a recognized treatment for different dystonia subtypes and has been approved by the Food and Drug Administration (FDA) since 2003. The European Federation of Neurological Societies (EFNS) and the International Parkinson and Movement Disorders Society (MDS) recommend DBS for dystonia after failure of botulinum toxin (BoNT) and other oral medications for dystonia treatment. In addition, several long-term studies have demonstrated the continuous efficacy of DBS on motor and quality of life (QoL) scores. However, there are only a few reports comparing the overall impact of surgical treatment in BoNT protocols (e.g., dosage and number of selected muscles before and after surgery). This retrospective multicenter chart-review study analyzed botulinum toxin total dosage and dosage per muscle in 23 dystonic patients before and after DBS surgery. The study's primary outcome was to analyze whether there was a reduction in BoNT dosage after DBS surgery. The mean BoNT dosages difference between baseline and post-surgery was 293.4 units for 6 months, 292.6 units for 12 months, and 295.2 units at the last visit. The median total dose of BoNT in the preoperative period was 800 units (N = 23). At the last visit, the median was 700 units (p = 0.05). This represents a 12.5% reduction in BoNT median dosage. In conclusion, despite the limitations of this retrospective study, there was a significant reduction in BoNT doses after DBS surgery in patients with generalized dystonia.

Wilson disease: the diagnostic challenge and treatment outcomes in a series of 262 cases.

BACKGROUND: Wilson disease (WD) is an autosomal recessive disorder that leads to organ toxicity due to copper overload. Early diagnosis is complicated by the rarity and diversity of manifestations. OBJECTIVE: To describe the diagnostic features and response to treatment in our cohort of WD patients. METHODS: This was a retrospective analysis of 262 WD patients stratified by clinical presentation, complementary exams, ATP7B genotyping, and response to treatment. RESULTS: Symptoms occurred at an average age of 17.4 (7-49) years, and patients were followed up for an average of 9.6 (0-45) years. Patients presented mainly with hepatic (36.3%), neurologic (34.7%), and neuropsychiatric (8.3%) forms. Other presentations were hematologic, renal, or musculoskeletal, and 16.8% of the patients were asymptomatic. Kayser-Fleischer rings occurred in 78.3% of the patients, hypoceruloplasminemia in 98.3%, and elevated cupruria/24h in 73.0%, with an increase after D-penicillamine in 54.0%. Mutations of the ATP7B gene were detected in 84.4% of alleles. Brain magnetic resonance imaging showed abnormalities in the basal ganglia in 77.7% of patients. D-penicillamine was the first choice in 93.6% of the 245 patients, and 21.1% of these patients were switched due to adverse effects. The second-line therapies were zinc and trientine. The therapeutic response did not differ significantly between the drugs (p = 0.2). Nine patients underwent liver transplantation and 82 died. CONCLUSION: Wilson disease is diagnosed at a late stage, and therapeutic options are limited. In people under 40 years of age with compatible manifestations, WD could be considered earlier in the differential diagnosis. There is a need to include ATP7B genotyping and therapeutic alternatives in clinical practice.

ANTECEDENTES: A doença de Wilson (DW) é um distúrbio autossômico recessivo caracterizado por acúmulo de cobre lesivo aos órgãos. O diagnóstico precoce é dificultado pela raridade e diversidade de apresentações. OBJETIVO: Descrever características ao diagnóstico e resposta ao tratamento em uma coorte de DW. MéTODOS: Análise retrospectiva de 262 casos de DW quanto à apresentação clínica, exames complementares, genotipagem e resposta ao tratamento. RESULTADOS: Os sintomas surgiram em uma média aos 17,4 (7­49) anos, e os pacientes foram acompanhados por uma média de 9,6 (0­45) anos. Os pacientes apresentaram principalmente formas hepáticas (36,3%), neurológicas (34,7%) e neuropsiquiátricas (8,3%). Outras apresentações foram hematológicas, renais e musculoesqueléticas. Apenas 16,8% eram assintomáticos. Anéis de Kayser-Fleischer ocorreram em 78,3% dos pacientes, hipoceruloplasminemia em 98,3%, e cuprúria elevada/24h em 73,0%, com aumento após D-penicilamina em 54,0%. Mutações do gene ATP7B foram detectadas em 84,4% dos alelos pesquisados. A ressonância magnética cerebral mostrou alterações em gânglios da base em 77,7% dos pacientes. O tratamento com D-penicilamina foi a escolha inicial em 93,6% dos 245 casos e foi trocado em 21,1% devido a efeitos adversos. Terapias de segunda linha foram zinco e trientina. A resposta terapêutica não diferiu significativamente entre os medicamentos (p = 0,2). Nove pacientes receberam transplante hepático e 82 faleceram. CONCLUSãO: O diagnóstico da DW ainda ocorre em estágios tardios, e as opções terapêuticas são limitadas. A DW deve ser considerada precocemente no diagnóstico diferencial de pessoas com menos de 40 anos com manifestações compatíveis. É necessário incorporar na prática clínica a genotipagem do ATP7B e alternativas terapêuticas à penicilamina.

Resolution of Wing-Beating Tremor and Magnetic Resonance Imaging Lesions in Wilson's Disease Following Penicillamine.

Background: The wing-beating tremor, characteristic of Wilson's disease (WD), is a disabling symptom that can be resistant to anti-copper and anti-tremor medications. Phenomenology Shown: This video illustrates severe bilateral wing-beating tremor, moderate head and lower limb tremors, mild cervical dystonia, and subtle cerebellar ataxia, with nearly resolution after penicillamine treatment. Educational Value: This case highlights a typical aspect of WD, emphasizing the importance of early detection and treatment, and its correlation with MRI findings. Highlights: This case highlights the typical wing-beating tremor in Wilson's disease and its correlation with the involvement of the dentato-rubro-thalamic pathway. The early diagnosis and initiation of treatment with penicillamine resulted in an excellent clinical and radiological response.

Trans-Spinal Theta Burst Magnetic Stimulation in Parkinson's Disease and Gait Disorders.

BACKGROUND: Gait disorders in patients with Parkinson's disease (PD) can become disabling with disease progression without effective treatment. OBJECTIVES: To investigate the efficacy of intermittent θ burst trans-spinal magnetic stimulation (TsMS) in PD patients with gait and balance disorders. METHODS: This was a randomized, parallel, double-blind, controlled trial. Active or sham TsMS was applied at third thoracic vertebra with 100% of the trans-spinal motor threshold, during 5 consecutive days. Participants were evaluated at baseline, immediately after last session, 1 and 4 weeks after last session. Primary outcome was Total Timed Up and Go (TUG) values comparing active versus sham phases 1 week after intervention. The secondary outcome measurements consisted of motor, gait and balance scales, and questionnaires for quality of life and cognition. RESULTS: Thirty-three patients were included, average age 68.5 (6.4) years in active group and 70.3 (6.3) years in sham group. In active group, Total TUG mean baseline was 107.18 (95% CI, 52.1-116.1), and 1 week after stimulation was 93.0 (95% CI, 50.7-135.3); sham group, Total TUG mean baseline was 101.2 (95% CI, 47.1-155.3) and 1 week after stimulation 75.2 (95% CI 34.0-116.4), P = 0.54. Similarly, intervention had no significant effects on secondary outcome measurements. During stimulation period, five patients presented with mild side effects (three in active group and two in sham group). DISCUSSION: TsMS did not significantly improve gait or balance analysis in patients with PD and gait disorders. The protocol was safe and well tolerated. © 2024 International Parkinson and Movement Disorder Society.

Mesencephalic Locomotor Region and Presynaptic Inhibition during Anticipatory Postural Adjustments in People with Parkinson's Disease.

Individuals with Parkinson's disease (PD) and freezing of gait (FOG) have a loss of presynaptic inhibition (PSI) during anticipatory postural adjustments (APAs) for step initiation. The mesencephalic locomotor region (MLR) has connections to the reticulospinal tract that mediates inhibitory interneurons responsible for modulating PSI and APAs. Here, we hypothesized that MLR activity during step initiation would explain the loss of PSI during APAs for step initiation in FOG (freezers). Freezers (n = 34) were assessed in the ON-medication state. We assessed the beta of blood oxygenation level-dependent signal change of areas known to initiate and pace gait (e.g., MLR) during a functional magnetic resonance imaging protocol of an APA task. In addition, we assessed the PSI of the soleus muscle during APA for step initiation, and clinical (e.g., disease duration) and behavioral (e.g., FOG severity and APA amplitude for step initiation) variables. A linear multiple regression model showed that MLR activity (R2 = 0.32, p = 0.0006) and APA amplitude (R2 = 0.13, p = 0.0097) explained together 45% of the loss of PSI during step initiation in freezers. Decreased MLR activity during a simulated APA task is related to a higher loss of PSI during APA for step initiation. Deficits in central and spinal inhibitions during APA may be related to FOG pathophysiology.

X-Linked Levodopa-Responsive Parkinsonism-Epilepsy Syndrome: A Novel PGK1 Mutation and Literature Review.

BACKGROUND: Genetic underpinnings in Parkinson's disease (PD) and parkinsonian syndromes are challenging, and recent discoveries regarding their genetic pathways have led to potential gene-specific treatment trials. CASES: We report 3 X-linked levodopa (l-dopa)-responsive parkinsonism-epilepsy syndrome cases due to a hemizygous variant in the phosphoglycerate kinase 1 (PGK1) gene. The likely pathogenic variant NM_000291.4 (PGK1):c.950G > A;p.(Gly317Asp) was identified in a hemizygous state. LITERATURE REVIEW: Only 8 previous cases have linked this phenotype to PGK1, a gene more commonly associated with hemolytic anemia and myopathy. The unusual association of epilepsy, psychiatric symptoms, action tremor, limb dystonia, cognitive symptoms, and l-dopa-responsive parkinsonism must draw attention to PGK1 mutations, especially because this gene is absent from most commercial hereditary parkinsonism panels. CONCLUSIONS: This report aims to shed light on an overlooked gene that causes hereditary parkinsonian syndromes. Further research regarding genetic pathways in PD may provide a better understanding of its pathophysiology and open possibilities for new disease-modifying trials, such as SNCA, LRRK2, PRKN, PINK1, and DJ-1 genes.

Probable 4-Repeat Tauopathy Criteria Predict Brain Amyloid Negativity, Distinct Clinical Features, and FDG-PET/MRI Neurodegeneneration Patterns in Corticobasal Syndrome.

BACKGROUND: Corticobasal syndrome (CBS) is associated with diverse underlying pathologies, including the four-repeat (4R)-tauopathies. The Movement Disorders Society (MDS) criteria for progressive supranuclear palsy (PSP) proposed the novel category "probable 4R-tauopathy" to address the phenotypic overlap between PSP and corticobasal degeneration (CBD). OBJECTIVES: To investigate the clinical ability of the MDS-PSP criteria for probable 4R-tauopathy in predicting a negative amyloid-PET in CBS. Additionally, this study aims to explore CBS patients classified as 4R-tauopathy concerning their clinical features and neuroimaging degeneration patterns. METHODS: Thirty-two patients with probable CBS were prospectively evaluated and split into those who fulfilled or did not fulfill the 4R-tauopathy criteria (CBS-4RT+ vs. CBS-4RT-). All patients underwent positron emission tomographies (PET) with [18 F]fluorodeoxyglucose and [11 C]Pittsburgh Compound-B (PIB) on a hybrid PET-MRI scanner to perform multimodal quantitative comparisons with a control group. RESULTS: Eleven patients were clinically classified as CBS-4RT+, and only one had a positive PIB-PET. The CBS-4RT+ classification had 92% specificity, 52% sensitivity, and 69% accuracy in predicting a negative PIB-PET. The CBS-4RT+ group presented with dysarthria and perseveration more often than the CBS-4RT- group. Moreover, the CBS-4RT+ group showed a prominent frontal hypometabolism extending to the supplementary motor area and striatum, and brain atrophy at the anterior cingulate and bilateral striata. CONCLUSIONS: The 4R-tauopathy criteria were highly specific in predicting a negative amyloid-PET in CBS. Patients classified as 4R-tauopathy presented distinct clinical aspects, as well as brain metabolism and atrophy patterns previously associated with tauopathies.

Average annual cost of Parkinson's disease in a Brazilian multiethnic population.

INTRODUCTION: With the current demographic transition, it is estimated that by 2050 Brazil will have a population of 90 million people aged 60 years or more, and in parallel Parkinson's disease (PD) will bring a considerable economic burden to our society. Brazil is considered multiracial due to its colonization, generating important social and regional inequalities. Knowing the costs of the PD may aid to improve local public policies. However, in Brazil, no estimates of these values have been made so far. OBJECTIVES: To evaluate direct, indirect, and out-of-pocket costs in Brazilian people with PD (PwP). METHODS: Categorical and numerical data were collected through a customized and standardized cost-related-questionnaire from 1055 PwP nationwide, from 10 tertiary movement disorders centers across all Brazilian regions. RESULTS: The estimated average annual cost of PwP was US$ 4020.48. Direct and indirect costs accounted for 63% and 36% of the total, respectively, and out-of-pocket costs were 49%. There were no evidence of differences in the total cost of PD across the regions of the country; however, differences were reported between the stages of the Hoehn and Yahr scale (H&Y). CONCLUSION: This data suggests a considerable burden of PD for Brazilian society in general, not only for the public health system, but mainly for those with PD.

Clinical assessment of upper limb impairments and functional capacity in Parkinson's disease: a systematic review / Avaliação clínica de comprometimentos de membros superiores e capacidade funcional na doença de Parkinson: uma revisão sistemática

Abstract Background Parkinson's disease (PD) may progressively reduce the upper limb's functionality. Currently, there is no standardized upper limb functional capacity assessment in PD in the rehabilitation field. Objective To identify specific outcome measurements to assess upper limbs in PD and access functional capacity. Methods We systematically reviewed and analyzed the literature in English published from August/2012 to August/2022 according to PRISMA. The following keywords were used in our search: "upper limbs" OR "upper extremity" and "Parkinson's disease." Two researchers searched independently, including studies accordingly to our inclusion and exclusion criteria. Registered at PROSPERO CRD42021254486. Results We found 797 studies, and 50 were included in this review (n = 2.239 participants in H&Y stage 1-4). The most common upper limbs outcome measures found in the studies were: (i) UPDRS-III and MDS-UPDRS to assess the severity and progression of PD motor symptoms (tremor, bradykinesia, and rigidity) (ii) Nine Hole Peg Test and Purdue Pegboard Test to assess manual dexterity; (iii) Spiral test and Funnel test to provoke and assess freezing of upper limbs; (iv) Technology assessment such as wearables sensors, apps, and other device were also found. Conclusion We found evidence to support upper limb impairments assessments in PD. However, there is still a large shortage of specific tests to assess the functional capacity of the upper limbs. The upper limbs' functional capacity is insufficiently investigated during the clinical and rehabilitation examination due to a lack of specific outcome measures to assess functionality.

Resumo Antecedentes A doença de Parkinson (DP) reduz progressivamente a funcionalidade do membro superior. Não existe uma avaliação padronizada da capacidade funcional do membro superior na DP na área da reabilitação. Objetivo Identificar medidas de resultados específicos para avaliar membros superiores na DP e avaliar capacidade funcional. Métodos Revisamos e analisamos sistematicamente a literatura publicada de agosto/2012 a agosto/2022 de acordo com PRISMA. Usamos as seguintes palavras-chave "membros superiores" OU "extremidade superior" e "doença de Parkinson." Dois pesquisadores fizeram a busca de forma independente, incluindo estudos de acordo com os critérios de inclusão e exclusão. Registro PROSPERO CRD42021254486. Resultados Encontramos 797 estudos, 50 foram incluídos no estudo(n = 2.239 participantes no estágio 1-4 de H&Y). As medidas de resultados de membros superiores mais comuns encontradas foram: (i) UPDRS-III e MDS-UPDRS, para avaliar a gravidade e a progressão dos sintomas motores da DP (tremor, bradicinesia, e rigidez); (ii) Nine Hole Peg Test e Purdue Pegboard Test para avaliar a destreza manual; (iii) Teste da Espiral e Teste do Funil para provocar e avaliar o congelamento de membros superiores; (iv) Avaliação de tecnologia, como sensores vestíveis, aplicativos e outros dispositivos também foram encontrados. Conclusão Encontramos evidências para dar suporte para as avaliações de deficiências de membros superiores na DP. No entanto, ainda há grande escassez de testes específicos para avaliar a capacidade funcional dos membros superiores. A capacidade funcional dos membros superior é insuficientemente investigada durante o exame clínico e de reabilitação devido à falta de medidas de resultados específicos para avaliar a funcionalidade.

Long-term tonic spinal cord stimulation in advanced Parkinson's disease: No effect from stimulation under placebo-controlled evaluation.

•Chronic spinal cord stimulation effectiveness was evaluated in four PD patients.•Double blinded cross over evaluation was performed using subthreshold stimulation.•An open label evaluation with regular suprathreshold stimulation was also performed.•No statistically significant effect was produced with either stimulation.•This study highlights the lack of strong clinical evidence supporting SCS for PD.

Clinical assessment of upper limb impairments and functional capacity in Parkinson's disease: a systematic review.

BACKGROUND: Parkinson's disease (PD) may progressively reduce the upper limb's functionality. Currently, there is no standardized upper limb functional capacity assessment in PD in the rehabilitation field. OBJECTIVE: To identify specific outcome measurements to assess upper limbs in PD and access functional capacity. METHODS: We systematically reviewed and analyzed the literature in English published from August/2012 to August/2022 according to PRISMA. The following keywords were used in our search: "upper limbs" OR "upper extremity" and "Parkinson's disease." Two researchers searched independently, including studies accordingly to our inclusion and exclusion criteria. Registered at PROSPERO CRD42021254486. RESULTS: We found 797 studies, and 50 were included in this review (n = 2.239 participants in H&Y stage 1-4). The most common upper limbs outcome measures found in the studies were: (i) UPDRS-III and MDS-UPDRS to assess the severity and progression of PD motor symptoms (tremor, bradykinesia, and rigidity) (ii) Nine Hole Peg Test and Purdue Pegboard Test to assess manual dexterity; (iii) Spiral test and Funnel test to provoke and assess freezing of upper limbs; (iv) Technology assessment such as wearables sensors, apps, and other device were also found. CONCLUSION: We found evidence to support upper limb impairments assessments in PD. However, there is still a large shortage of specific tests to assess the functional capacity of the upper limbs. The upper limbs' functional capacity is insufficiently investigated during the clinical and rehabilitation examination due to a lack of specific outcome measures to assess functionality.

ANTECEDENTES: A doença de Parkinson (DP) reduz progressivamente a funcionalidade do membro superior. Não existe uma avaliação padronizada da capacidade funcional do membro superior na DP na área da reabilitação. OBJETIVO: Identificar medidas de resultados específicos para avaliar membros superiores na DP e avaliar capacidade funcional. MéTODOS: Revisamos e analisamos sistematicamente a literatura publicada de agosto/2012 a agosto/2022 de acordo com PRISMA. Usamos as seguintes palavras-chave "membros superiores" OU "extremidade superior" e "doença de Parkinson." Dois pesquisadores fizeram a busca de forma independente, incluindo estudos de acordo com os critérios de inclusão e exclusão. Registro PROSPERO CRD42021254486. RESULTADOS: Encontramos 797 estudos, 50 foram incluídos no estudo(n = 2.239 participantes no estágio 1­4 de H&Y). As medidas de resultados de membros superiores mais comuns encontradas foram: (i) UPDRS-III e MDS-UPDRS, para avaliar a gravidade e a progressão dos sintomas motores da DP (tremor, bradicinesia, e rigidez); (ii) Nine Hole Peg Test e Purdue Pegboard Test para avaliar a destreza manual; (iii) Teste da Espiral e Teste do Funil para provocar e avaliar o congelamento de membros superiores; (iv) Avaliação de tecnologia, como sensores vestíveis, aplicativos e outros dispositivos também foram encontrados. CONCLUSãO: Encontramos evidências para dar suporte para as avaliações de deficiências de membros superiores na DP. No entanto, ainda há grande escassez de testes específicos para avaliar a capacidade funcional dos membros superiores. A capacidade funcional dos membros superior é insuficientemente investigada durante o exame clínico e de reabilitação devido à falta de medidas de resultados específicos para avaliar a funcionalidade.

Exploring the levodopa-paradox of freezing of gait in dopaminergic medication-naïve Parkinson's disease populations.

The relationship between dopaminergic treatment and freezing of gait (FOG) in Parkinson's disease (PD) is complex: levodopa is the most effective symptomatic treatment for FOG, but long-term pulsatile levodopa treatment has also been linked to an increase in the occurrence of FOG. This concept, however, continues to be debated. Here, we compared the occurrence of FOG between a levodopa-naive PD cohort and a levodopa-treated cohort. Forty-nine treatment-naive patients and 150 levodopa-treated patients were included. The time since first motor symptoms was at least 5 years. Disease severity was assessed using the MDS-UPDRS part III. Occurrence of FOG was assessed subjectively (new freezing-of-gait-questionnaire) and objectively (rapid turns test and Timed Up-and-Go test). The presence of FOG was compared between the levodopa-treated and levodopa-naive groups using a chi-square test of homogeneity. We also performed a binomial Firth logistic regression with disease duration, disease severity, country of inclusion, location of measurement, and executive function as covariates. Subjective FOG was more common in the levodopa-treated cohort (n = 41, 27%) compared to the levodopa-naive cohort (n = 2, 4%, p < 0.001). The association between FOG and levodopa treatment remained after adjustment for covariates (OR = 6.04, 95%Cl [1.60, 33.44], p = 0.006). Objectively verified FOG was more common in the levodopa-treated cohort (n = 21, 14%) compared to the levodopa-naive cohort (n = 1, 2%, p = 0.02). We found an association between long-term pulsatile levodopa treatment and an increased occurrence of FOG. Future studies should further explore the role of nonphysiological stimulation of dopamine receptors in generating FOG, as a basis for possible prevention studies.

Handicap as a Measure of Perceived-Health Status in Parkinson's Disease.

Background: Handicap is a patient-centered measure of health status that encompasses the impact of social and physical environment on daily living, having been assessed in advanced and late-stage Parkinson's Disease (PD). Objective: To characterize the handicap of a broader sample of patients. Methods: A cross-sectional study of 405 PD patients during the MDS-UPDRS Portuguese validation study, using the MDS-UPDRS, Unified Dyskinesias Rating Scale, Nonmotor symptoms questionnaire, PDQ-8 and EQ-5D-3L. Handicap was measured using the London Handicap Scale (LHS). Results: Mean age was 64.42 (±10.3) years, mean disease duration 11.30 (±6.5) years and median HY 2 (IQR, 2-3). Mean LHS was 0.652 (±0.204); "Mobility," "Occupation" and "Physical Independence" were the most affected domains. LHS was significantly worse in patients with longer disease duration, older age and increased disability. In contrast, PDQ-8 did not differentiate age groups. Handicap was significantly correlated with disease duration (r = -0.35), nonmotor experiences of daily living (EDL) (MDS-UPDRS-I) (r = -0.51), motor EDL (MDS-UPDRS-II) (r = -0.69), motor disability (MDS-UPDRS-III) (r = -0.49), axial signs of MDS-UPDRS-III (r = -0.55), HY (r = -0.44), presence of nonmotor symptoms (r = -0.51) and PDQ-8 index (r = -0.64) (all P < 0.05). Motor EDL, MDS-UPDRS-III and PDQ-8 independently predicted Handicap (adjusted R 2 = 0.582; P = 0.007). Conclusions: The LHS was easily completed by patients and caregivers. Patients were mild-moderately handicapped, which was strongly determined by motor disability and its impact on EDL, and poor QoL. Despite correlated, handicap and QoL seem to differ in what they measure, and handicap may have an added value to QoL. Handicap seems to be a good measure of perceived-health status in a broad sample of PD.

Parkinson's Disease-related Pains are Not Equal: Clinical, Somatosensory and Cortical Excitability Findings in Individuals With Nociceptive Pain.

Chronic pain is a frequent and burdensome nonmotor symptom of Parkinson's disease (PD). PD-related chronic pain can be classified as nociceptive, neuropathic, or nociplastic, the former being the most frequent subtype. However, differences in neurophysiologic profiles between these pain subtypes, and their potential prognostic and therapeutic implications have not been explored yet. This is a cross-sectional study on patients with PD (PwP)-related chronic pain (ie, started with or was aggravated by PD). Subjects were assessed for clinical and pain characteristics through questionnaires and underwent quantitative sensory tests and motor corticospinal excitability (CE) evaluations. Data were then compared between individuals with nociceptive and non-nociceptive (ie, neuropathic or nociplastic) pains. Thirty-five patients were included (51.4% male, 55.7 ± 11.0 years old), 20 of which had nociceptive pain. Patients with nociceptive PD-related pain had lower warm detection threshold (WDT, 33.34 ± 1.39 vs 34.34 ± 1.72, P = .019) and mechanical detection threshold (MDT, 2.55 ± 1.54 vs 3.86 ± .97, P = .007) compared to those with non-nociceptive pains. They also presented a higher proportion of low rest motor threshold values than the non-nociceptive pain ones (64.7% vs 26.6%, P = .048). In non-nociceptive pain patients, there was a negative correlation between WDT and non-motor symptoms scores (r = -.612, P = .045) and a positive correlation between MDT and average pain intensity (r = .629, P = .038), along with neuropathic pain symptom scores (r = .604, P = .049). It is possible to conclude that PD-related chronic pain subtypes have distinctive somatosensory and CE profiles. These preliminary data may help better frame previous contradictory findings in PwP and may have implications for future trial designs aiming at developing individually-tailored therapies. PERSPECTIVE: This work showed that PwP-related nociceptive chronic pain may have distinctive somatosensory and CE profiles than those with non-nociceptive pain subtypes. These data may help shed light on previous contradictory findings in PwP and guide future trials aiming at developing individually-tailored management strategies.

Development and Validation of the Dystonia-Pain Classification System: A Multicenter Study.

BACKGROUND: Dystonia is associated with disabling nonmotor symptoms like chronic pain (CP), which is prevalent in dystonia and significantly impacts the quality of life (QoL). There is no validated tool for assessing CP in dystonia, which substantially hampers pain management. OBJECTIVE: The aim was to develop a CP classification and scoring system for dystonia. METHODS: A multidisciplinary group was established to develop the Dystonia-Pain Classification System (Dystonia-PCS). The classification of CP as related or unrelated to dystonia was followed by the assessment of pain severity score, encompassing pain intensity, frequency, and impact on daily living. Then, consecutive patients with inherited/idiopathic dystonia of different spatial distribution were recruited in a cross-sectional multicenter validation study. Dystonia-PCS was compared to validated pain, mood, QoL, and dystonia scales (Brief Pain Inventory, Douleur Neuropathique-4 questionnaire, European QoL-5 Dimensions-3 Level Version, and Burke-Fahn-Marsden Dystonia Rating Scale). RESULTS: CP was present in 81 of 123 recruited patients, being directly related to dystonia in 82.7%, aggravated by dystonia in 8.8%, and nonrelated to dystonia in 7.5%. Dystonia-PCS had excellent intra-rater (Intraclass Correlation Coefficient - ICC: 0.941) and inter-rater (ICC: 0.867) reliability. In addition, pain severity score correlated with European QoL-5 Dimensions-3 Level Version's pain subscore (r = 0.635, P < 0.001) and the Brief Pain Inventory's severity and interference scores (r = 0.553, P < 0.001 and r = 0.609, P < 0.001, respectively). CONCLUSIONS: Dystonia-PCS is a reliable tool to categorize and quantify CP impact in dystonia and will help improve clinical trial design and management of CP in patients affected by this disorder. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.