RESUMO
People with Parkinson's disease often show deficits in dexterity, which, in turn, can lead to limitations in performing activities of daily life. Previous studies have suggested that training in playing the piano may improve or prevent a decline in dexterity in this population. In this pilot study, we tested three participants on a six-week, custom, piano-based training protocol, and quantified dexterity before and after the intervention using a sensor-enabled version of the nine-hole peg test, the box and block test, a test of finger synergies using unidimensional force sensors, and the Quantitative Digitography test using a digital piano, as well as selected relevant items from the motor parts of the MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and the Parkinson's Disease Questionnaire (PDQ-39) quality of life questionnaire. The participants showed improved dexterity following the training program in several of the measures used. This pilot study proposes measures that can track changes in dexterity as a result of practice in people with Parkinson's disease and describes a potential protocol that needs to be tested in a larger cohort.
Assuntos
Doença de Parkinson , Humanos , Doença de Parkinson/fisiopatologia , Projetos Piloto , Masculino , Idoso , Feminino , Qualidade de Vida , Pessoa de Meia-Idade , Destreza Motora/fisiologia , Música , Inquéritos e Questionários , Atividades Cotidianas , Dedos/fisiologia , Dedos/fisiopatologiaRESUMO
Alexander disease (AxD) is a rare autosomal dominant leukodystrophy caused by heterozygous mutations in the glial fibrillary acid protein (GFAP) gene. The age of symptoms onset ranges from infancy to adulthood, with variable clinical and radiological manifestations. Adult-onset AxD manifests as a chronic and progressive condition, characterized by bulbar, motor, cerebellar, and other clinical signs and symptoms. Neuroradiological findings typically involve the brainstem and cervical spinal cord. Adult-onset AxD has been described in diverse populations but is rare in Israel. We present a series of patients diagnosed with adult-onset AxD from three families, all of Jewish Syrian descent. Five patients (4 females) were diagnosed with adult-onset AxD due to the heterozygous mutation c.219G > A, p.Met73Ile in GFAP. Age at symptoms onset ranged from 48 to 61 years. Clinical characteristics were typical and involved progressive bulbar and gait disturbance, followed by pyramidal and cerebellar impairment, dysautonomia, and cognitive decline. Imaging findings included medullary and cervical spinal atrophy and mostly infratentorial white matter hyperintensities. A newly recognized cluster of adult-onset AxD in Jews of Syrian origin is presented. This disorder should be considered in differential diagnosis in appropriate circumstances. Genetic counselling for family members is required in order to discuss options for future family planning.
Assuntos
Doença de Alexander , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Doença de Alexander/diagnóstico por imagem , Doença de Alexander/genética , Judeus/genética , Síria , Proteína Glial Fibrilar Ácida/genética , Mutação , AtrofiaRESUMO
BACKGROUND: Deep brain stimulation (DBS) is a well-established treatment option for individuals with advanced Parkinson's disease (PD). The potential influence of the LRRK2 p.G2019S or GBA1 variants on its lasting efficacy and adverse effects should be better characterized. METHODS: We conducted a retrospective single-center case-control study involving PD patients who were carriers of a GBA1 variant (GBA1-PD), the LRRK2 p.G2019S variant (LRRK2-PD), and non-carriers (Nc-PD). All participants underwent DBS and were followed up for at least a year. Assessments before surgery and at 1, 2, 3, 5, and 10 years post-DBS included the following: the Movement Disorder Society's Unified PD Rating Scale (MDS-UPDRS) Part III, Hoehn and Yahr scale, Levodopa Equivalent Daily Dose (LEDD) and non-motor symptoms (psychotic episodes, depressive symptoms, and cognitive decline). RESULTS: The sample was composed of 103 patients (72 males, mean age at DBS surgery 61.5 ± 8.7 years, mean postoperative follow-up 7.0 ± 4.1 years). Of these, 19 were LRRK2-PD, 20 GBA1-PD, and 64 were Nc-PD. No significant differences in motor outcomes were observed between the groups. Compared to the Nc-PD patients, the GBA1-PD patients were at increased risk of both psychotic episodes [hazard ratio (HR) 2.76 (95 % CI: 1.12-6.80), p = 0.027], and cognitive decline [HR 2.28 (95 % CI: 1.04-5.00), p = 0.04]. CONCLUSION: LRRK2 and GBA1 variant status did not affect the motor outcomes of DBS in PD patients. However, GBA1-PD patients were at increased risk for psychosis and cognitive decline. Further studies are required to determine the role of genetic stratification in referral to DBS.
Assuntos
Estimulação Encefálica Profunda , Glucosilceramidase , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Doença de Parkinson , Humanos , Doença de Parkinson/terapia , Doença de Parkinson/genética , Estimulação Encefálica Profunda/efeitos adversos , Masculino , Feminino , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Glucosilceramidase/genética , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Estudos de Casos e Controles , Resultado do Tratamento , SeguimentosRESUMO
BACKGROUND: Whole-plant medical cannabis (MC) products are widely used for controlling symptoms associated with Parkinson's disease (PD). Despite its widespread use, few studies have investigated the long-term impact of MC on the progression of PD or its safety profile. This study examined the effects of MC on PD in a real-life setting. METHODS: A retrospective case-control study of 152 idiopathic PD patients (mean age 69.1 ± 9.0 years), followed at the Sheba Medical Center Movement Disorders Institute (SMDI) from 2008 to 2022 was conducted. Seventy-six patients who used licensed whole-plant medical cannabis (MC) for at least a year were compared to a matched group who did not receive MC in terms of their Levodopa Equivalent Daily Dose (LEDD), Hoehn and Yahr (H&Y) stage, and cognitive, depressive, and psychotic symptoms. RESULTS: The median monthly dose of MC was 20 g (IQR: 20-30), with a median Tetrahydrocannabinol (THC) percentage of 10 (IQR: 9.5-14.15) and a median Cannabidiol (CBD) percentage of 4 (IQR: 2-10). There were no significant differences between the MC and the control groups for LEDD or H&Y stage progression (p = 0.90, 0.77, respectively). A Kaplan-Meier analysis showed no evidence of relative worsening of psychotic, depressive, or cognitive symptoms reported by patients to their treating physicians over time in the MC group (p = 0.16-0.50). CONCLUSION: Over the 1-3 years of follow-ups, the MC treatment regimens appeared to be safe. MC did not exacerbate neuropsychiatric symptoms and had no detrimental effects on disease progression.
Assuntos
Maconha Medicinal , Doença de Parkinson , Humanos , Pessoa de Meia-Idade , Idoso , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico , Maconha Medicinal/efeitos adversos , Estudos Retrospectivos , Estudos de Casos e Controles , Levodopa/uso terapêuticoRESUMO
Botulinum toxin (BT) injections into the cervical muscles are an effective and commonly practiced treatment approach for cervical dystonia. In this retrospective longitudinal study, we collected data from the Sheba electronic medical records on consecutive patients with idiopathic cervical dystonia (ICD), treated regularly with periodic BT injections between the years 2008-2020. All treatment visits were analyzed regarding type of toxin, dose injected, and clinical outcomes. The vast majority of patients were treated with abobotulinum toxin A. Sixty-four ICD patients (51 (79.7%) females, onset at age 45.8 ± 13.7 years) were treated over 17.1 ± 13.9 (range 3 to 49) visits per patient; BT treatment efficacy increased gradually from initial treatment sessions to visit 13, when it achieved a steady state. While the subjective report of percentage improvement and its duration were around 78.9 ± 17.1% for 2.8 ± 1.0 months, respectively, the dose of BT increased significantly over the years (p = 0.006). Side effects (SE) were not rare, and commonly recurred after subsequent sessions and were usually mild and short-lasting, with dysphagia being the most common (~17.5%), followed by neck/arm weakness (11.9%) and cervical pain (8.9%). Repeated injections of BT for ICD remain beneficial for patients over several years of therapy, and despite mild SE, patients tend to adhere to a 3-4 months interval schedule.
Assuntos
Toxinas Botulínicas/administração & dosagem , Torcicolo/diagnóstico , Torcicolo/tratamento farmacológico , Inibidores da Liberação da Acetilcolina/administração & dosagem , Adulto , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Torcicolo/fisiopatologiaRESUMO
OBJECTIVES: We aimed to characterize parkinsonian features and gait performance of psychiatric patients on neuroleptics (PPN) and to compare them to Parkinson's disease (PD) and healthy controls (HC). METHODS: Hospitalized PPN (n = 27) were recruited, examined, and rated for parkinsonian signs according to the motor part of the Movement Disorders Society Unified Parkinson's Disease Rating Scale and performed a 10-m "timed-up-and-go" (TUG) test with a smartphone-based motion capture system attached to their sternum. Gait parameters and mUPDRS scores were compared to those of consecutive age-matched PD patients (n = 18) and HC (n = 27). RESULTS: Psychiatric patients on neuroleptics exhibited parkinsonism (mUPDRS score range: 8-44) but less than that of PD patients (18.2 ± 9.2 vs 29.8 ± 10.3, P = 0.001). TUG times were slower for PPN and PD versus HC (total: 30.6 ± 7.6 seconds vs 30.0 ± 7.3 seconds vs 20.0 ± 3.2 seconds, straight walking: 10.6 ± 2.7 seconds vs 10.6 ± 2.4 seconds vs 6.8 ± 1.2 seconds) (P < 0.001), and cadence and step length were similar among PPN and PD and different from HC as well. Although their gait speed was slower than HC but similar to PD, PPN had lower mediolateral sway (4.3 ± 1.1 cm vs 6.7 ± 2.9 cm vs 6.9 ± 2.9 cm, respectively, P < 0.001) than both. CONCLUSIONS: Parkinsonism is very common in hospitalized PPN, but usually milder than that of PD. It seems that wearable sensor-based technology for assessing gait and balance may present a more sensitive and quantitative tool to detect clinical aspects of neuroleptic-induced parkinsonism than standard clinical ratings.
Assuntos
Antipsicóticos/efeitos adversos , Análise da Marcha/estatística & dados numéricos , Transtornos Mentais/complicações , Transtornos Mentais/fisiopatologia , Doença de Parkinson Secundária/fisiopatologia , Doença de Parkinson/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antipsicóticos/uso terapêutico , Estudos de Casos e Controles , Feminino , Análise da Marcha/métodos , Humanos , Pacientes Internados , Masculino , Transtornos Mentais/tratamento farmacológico , Pessoa de Meia-Idade , Monitorização Ambulatorial/métodos , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/complicações , Adulto JovemRESUMO
INTRODUCTION: The clinical characteristics of Parkinson's disease (PD) associated with both the LRRK2 p.G2019S mutation and a GBA variant (LRRK2-GBA-PD) have not yet been determined. METHODS: In this retrospective observational study of Ashkenazi-Jewish (AJ) PD patients, we describe the clinical course and characteristics of LRRK2-GBA-PD and estimate the risk to develop PD for the double mutation carriers. Odds ratios (OR) were estimated using published data on frequencies of GBA and LRRK2 mutations. Demographic and clinical data was retrieved from medical records and from rating at last visit. RESULTS: Our analysis included 236 PD patients, divided into four groups: LRRK2-PD (nâ¯=â¯66), GBA-PD (nâ¯=â¯78), GBA-LRRK2-PD (nâ¯=â¯12) and mutation-negative PD (MNPD, nâ¯=â¯80 randomly selected). The estimated ORs in different models for GBA-LRRK2 PD were 15-28 (95% CI 6.7-72.0, pâ¯<â¯0.0001), compared to AJ controls. Using logistic regression (while controlling for sex, age at onset and PD duration), we found that probable REM-sleep behavior disorder (RBD) was significantly more common for GBA-PD than for LRRK2-PD, while none of the GBA-LRRK2-PD patients reported RBD. Dementia was significantly more common for GBA-PD than for the LRRK2-PD and MNPD. Psychosis was the most common for GBA-PD and least common for LRRK2-GBA-PD. CONCLUSIONS: While GBA-PD is characterized by higher rates of dementia, probable RBD and psychosis, it seems that compared to the other groups, these features are less common for LRRK2-GBA-PD. This may imply to a possible protective effect of LRRK2 p.G2019S mutation among GBA variant carriers.
Assuntos
Estudos de Associação Genética/métodos , Predisposição Genética para Doença/genética , Glucosilceramidase/genética , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Mutação/genética , Doença de Parkinson/genética , Adulto , Idoso , Estudos de Coortes , Feminino , Heterozigoto , Humanos , Judeus/genética , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Variants in GBA are the most common genetic risk factor for Parkinson's disease (PD), and are especially prevalent in the Ashkenazi Jewish (AJ) population. However, most studies on GBA in AJ genotype only seven selected Gaucher-associated pathogenic variants rather than sequencing the whole gene, which may leave carriers of PD-associated GBA variants undiscovered. METHODS: GBA was fully sequenced using molecular inversion probes (MIPs) and Sanger sequencing in 735 AJ PD patients and 662 AJ controls, from Israel and New York. Additional AJ control data (nâ¯=â¯3044) from the Inflammatory Bowel Disease Exome Portal was used. RESULTS: Full GBA sequencing increased the number of variants discovered by 17.4%, compared to targeted genotyping. An additional 17 PD patients were identified with GBA-associated PD. The p.E326K variant was found in 1.6% of AJ PD patients, making it the second most common PD-associated GBA variant in AJ. GBA variants were found in 18% of PD patients and 7.5% of controls (ORâ¯=â¯2.7, 95%CIâ¯=â¯1.9-3.8, pâ¯<â¯0.0001). CONCLUSION: Without full sequencing of GBA, or at minimum including p.E326K in the genotyping panel, a significant proportion of variant carriers go undiscovered and may be incorrectly assigned as non-carriers in studies or clinical trials.