RESUMO
BACKGROUND: GBA variants increase the risk of developing Parkinson disease (PD) and influence its outcome. Deep brain stimulation (DBS) is a recognised therapeutic option for advanced PD. Data on DBS long-term outcome in GBA carriers are scarce. OBJECTIVE: To elucidate the impact of GBA variants on long-term DBS outcome in a large Italian cohort. METHODS: We retrospectively recruited a multicentric Italian DBS-PD cohort and assessed: (1) GBA prevalence; (2) pre-DBS clinical features; and (3) outcomes of motor, cognitive and other non-motor features up to 5 years post-DBS. RESULTS: We included 365 patients with PD, of whom 73 (20%) carried GBA variants. 5-year follow-up data were available for 173 PD, including 32 mutated subjects. GBA-PD had an earlier onset and were younger at DBS than non-GBA-PD. They also had shorter disease duration, higher occurrence of dyskinesias and orthostatic hypotension symptoms.At post-DBS, both groups showed marked motor improvement, a significant reduction of fluctuations, dyskinesias and impulsive-compulsive disorders (ICD) and low occurrence of most complications. Only cognitive scores worsened significantly faster in GBA-PD after 3 years. Overt dementia was diagnosed in 11% non-GBA-PD and 25% GBA-PD at 5-year follow-up. CONCLUSIONS: Evaluation of long-term impact of GBA variants in a large Italian DBS-PD cohort supported the role of DBS surgery as a valid therapeutic strategy in GBA-PD, with long-term benefit on motor performance and ICD. Despite the selective worsening of cognitive scores since 3 years post-DBS, the majority of GBA-PD had not developed dementia at 5-year follow-up.
Assuntos
Estimulação Encefálica Profunda , Demência , Discinesias , Doença de Parkinson , Humanos , Doença de Parkinson/genética , Doença de Parkinson/terapia , Doença de Parkinson/complicações , Estudos Retrospectivos , Discinesias/terapia , Demência/complicações , ItáliaRESUMO
BACKGROUND AND PURPOSE: Treatment of freezing of gait (FoG) and other Parkinson disease (PD) axial symptoms is challenging. Systematic assessments of axial symptoms at progressively increasing levodopa doses are lacking. We sought to analyze the resistance to high levodopa doses of FoG, posture, speech, and altered gait features presenting in daily-ON therapeutic condition. METHODS: We performed a pre-/postinterventional study including patients treated with levodopa/carbidopa intestinal gel infusion (LCIG) with disabling FoG in daily-ON condition. Patients were evaluated at their usual LCIG infusion rate (T1), and 1 h after 1.5× (T2) and 2× (T3) increase of the LCIG infusion rate by quantitative outcome measures. The number of FoG episodes (primary outcome), posture, speech, and gait features were objectively quantified during a standardized test by a blinded rater. Changes in motor symptoms, dyskinesia, and plasma levodopa concentrations were also analyzed. RESULTS: We evaluated 16 patients with a mean age of 69 ± 9.4 years and treated with LCIG for a mean of 2.2 ± 2.1 years. FoG improved in 83.3% of patients by increasing the levodopa doses. The number of FoG episodes significantly decreased (mean = 2.3 at T1, 1.7 at T2, 1.2 at T3; p = 0.013). Posture and speech features did not show significant changes, whereas stride length (p = 0.049), turn duration (p = 0.001), and turn velocity (p = 0.024) significantly improved on doubling the levodopa infusion rate. CONCLUSIONS: In a short-term evaluation, the increase of LCIG dose can improve "dopa-resistant" FoG and gait issues in most advanced PD patients with overall good control of motor symptoms in the absence of clinically significant dyskinesia.
Assuntos
Discinesias , Transtornos Neurológicos da Marcha , Doença de Parkinson , Humanos , Pessoa de Meia-Idade , Idoso , Levodopa , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico , Antiparkinsonianos/efeitos adversos , Transtornos Neurológicos da Marcha/tratamento farmacológico , Transtornos Neurológicos da Marcha/etiologia , Carbidopa , Géis/uso terapêutico , Combinação de Medicamentos , Postura , Discinesias/tratamento farmacológicoRESUMO
INTRODUCTION: Parkinson's Disease (PD) patients with Parkin gene (PRKN) mutations show good response to subthalamic deep brain stimulation (STN-DBS). Currently, the longest follow-up available of these patients is 6 years. We report a very long-term outcome (more than 15 years) of a STN-DBS-treated patient with a compound heterozygous deletion of exons 3 and 11 of the PRKN gene. CASE REPORT: In 1993, a 39-year-old male was diagnosed with PD after the onset of resting tremor. Levodopa was started, and during the following 10 years, he reported good motor symptoms control, with only mild modification of levodopa intake and pramipexole introduction. In 2005, he developed disabling motor fluctuations and dyskinesia. In 2007, he underwent bilateral STN-DBS, with a marked improvement of motor symptoms and fluctuations during the following years. After 6 years, he reported mild motor fluctuations, improved after stimulation and treatment modifications. After 10 years he showed diphasic dyskinesias, feet dystonia, postural instability, and gambling (resolved after pramipexole discontinuation). In 2018, he developed a non-amnestic single-domain mild cognitive impairment (MCI). In 2023, after more than 15 years of STN-DBS, motor symptoms and fluctuations are still well controlled. He reports mild dysphagia, mild depression, and multiple-domain MCI. His quality of life is better than before surgery, and he still reports a subjective significant improvement from STN-DBS. CONCLUSION: Confirming the very long-term efficacy of STN-DBS in PRKN-mutated patients, our case report underlines their peculiar suitability for surgical treatment.
Assuntos
Estimulação Encefálica Profunda , Discinesias , Doença de Parkinson , Núcleo Subtalâmico , Masculino , Humanos , Adulto , Doença de Parkinson/genética , Doença de Parkinson/terapia , Doença de Parkinson/diagnóstico , Levodopa/uso terapêutico , Pramipexol/uso terapêutico , Qualidade de Vida , Núcleo Subtalâmico/cirurgia , Mutação , Discinesias/terapia , Resultado do TratamentoRESUMO
Axial postural abnormalities (aPA) are common features of Parkinson's disease (PD) and manifest in over 20% of patients during the course of the disease. aPA form a spectrum of functional trunk misalignment, ranging from a typical Parkinsonian stooped posture to progressively greater degrees of spine deviation. Current research has not yet led to a sufficient understanding of pathophysiology and management of aPA in PD, partially due to lack of agreement on validated, user-friendly, automatic tools for measuring and analysing the differences in the degree of aPA, according to patients' therapeutic conditions and tasks. In this context, human pose estimation (HPE) software based on deep learning could be a valid support as it automatically extrapolates spatial coordinates of the human skeleton keypoints from images or videos. Nevertheless, standard HPE platforms have two limitations that prevent their adoption in such a clinical practice. First, standard HPE keypoints are inconsistent with the keypoints needed to assess aPA (degrees and fulcrum). Second, aPA assessment either requires advanced RGB-D sensors or, when based on the processing of RGB images, they are most likely sensitive to the adopted camera and to the scene (e.g., sensor-subject distance, lighting, background-subject clothing contrast). This article presents a software that augments the human skeleton extrapolated by state-of-the-art HPE software from RGB pictures with exact bone points for posture evaluation through computer vision post-processing primitives. This article shows the software robustness and accuracy on the processing of 76 RGB images with different resolutions and sensor-subject distances from 55 PD patients with different degrees of anterior and lateral trunk flexion.
Assuntos
Doença de Parkinson , Humanos , Doença de Parkinson/diagnóstico , Postura/fisiologia , Software , Gravação de Videoteipe , Osso e Ossos , Equilíbrio Postural/fisiologiaRESUMO
PURPOSE: We sought to estimate the impact of cardiovascular autonomic neuropathy (cAN) on informal caregivers of patients with Parkinson's disease (PD), defined as individuals providing regular care to a friend, partner, or family member with PD, and to evaluate the mutual relationship between caregiver burden and patient health-related quality of life (HRQoL). METHODS: We enrolled 36 consecutive patients with PD and their informal caregivers. Patients underwent a detailed motor, autonomic, cognitive, and functional assessment. Caregivers were assessed using the Zarit Burden Interview (ZBI). Differences in caregiver burden, expressed by the ZBI score, and strength of association between caregiver burden, cAN, and HRQoL were assessed using analysis of covariance (ANCOVA), logistic regression, and linear regression analyses. Analyses were adjusted for patients' age, PD duration, and motor and cognitive disability, as well as caregivers' age. RESULTS: Moderate-severe caregiver burden was reported in 41.7% of PDcAN+ versus 8.7% of PDcAN- (p < 0.001). The ZBI score was increased in PDcAN+ versus PDcAN- (31.5 ± 3.4 versus 15.2 ± 2.3; p < 0.001), with tenfold higher odds (p = 0.012) of moderate-severe caregiver burden in PDcAN+, even after adjusting for potential confounders. The ZBI score correlated with cAN severity (p = 0.005), global autonomic impairment (p = 0.012), and HRQoL impairment (p < 0.001). CONCLUSION: These results highlight the significant impact of cAN on PD caregivers and the need for targeted interventions addressing this frequently overlooked and insufficiently treated source of nonmotor disability in PD.
Assuntos
Doença de Parkinson , Disautonomias Primárias , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/terapia , Qualidade de Vida , Efeitos Psicossociais da Doença , Cuidadores/psicologia , Disautonomias Primárias/etiologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The psychological impact of the COVID-19 outbreak and lockdown on frail populations with advanced Parkinson disease (APD) and their caregivers may present with peculiar features and require specific interventions. METHODS: We enrolled here 100 APD patients and 60 caregivers. Seventy-four patients were treated with device-aided therapies (DAT) and 26 with standard medical treatment (SMT). Through a telephonic interview, subjects underwent the Hospital Anxiety and Depression Scale (HADS-A; HADS-D), and an ad hoc questionnaire to explore thoughts and emotions related to the pandemic. RESULTS: Depression was observed in 35% of APD patients and anxiety in 39%, with a significant reduction of the latter after the lockdown (p= 0.023). We found a significant correlation between the type of therapy and the HADS-A score (p= 0.004). Patients' main worries were as follows: a possible higher risk of COVID-19 infection (25%), interruption of non-pharmacological treatments (35%), interruption of outpatient clinics (38%), PD complications related to COVID-19 (47%). Patients treated with DAT manifested worries about device-related issues and risk for caregivers' infection. The 40% of caregivers showed anxiety, while the 21.7% of them showed depression. CONCLUSION: Our study reveals a higher prevalence of anxiety and the presence of peculiar worries and needs in APD patients during the pandemic alongside psychological sequelae of their caregivers. These findings are important for neurologists and healthcare services to foster strategies for the management of psychological distress in both patients and caregivers.
Assuntos
COVID-19 , Doença de Parkinson , Ansiedade/epidemiologia , Controle de Doenças Transmissíveis , Depressão/epidemiologia , Humanos , Pandemias , Doença de Parkinson/epidemiologia , Doença de Parkinson/terapia , SARS-CoV-2 , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Several neurological complications have been reported following SARS-Cov-2 vaccination, without a clear causal relationship ever being verified, including some cases of worsening of Parkinson's disease (PD) symptoms and new onset of movement disorders in non-parkinsonian patients. METHODS: We describe two new cases of PD patients treated with device-aided therapy who developed worsening of parkinsonian symptoms after receiving the third vaccine dose (booster). We also conducted a short review of the cases reported in literature of PD symptoms worsening and new onset of movement disorders in non-parkinsonian patients after SARS-Cov-2 vaccination. RESULTS: The first patient, a 46-year-old man implanted with bilateral Subthalamic Deep Brain Stimulation, experienced temporary motor and non-motor symptoms worsening after mRNA-1273 booster, improved after stimulation settings modification. The second patient, a 55-year-old man implanted with percutaneous endoscopic transgastric jejunostomy (PEG-J) for levodopa-carbidopa intestinal gel (LCIG) infusion experienced severe temporary worsening of dyskinesia and managed through temporary LCIG dose reduction. Other seven cases of vaccine-related movement disorder are currently reported in literature, four describing PD symptoms worsening and three the onset of new movement disorders in otherwise healthy people. CONCLUSION: Both our patients and the cases described so far completely recovered after few days with parkinsonian therapy modification, symptomatic treatment, or even spontaneously, underlining the transient and benign nature of side effects from vaccine. Patients should be reassured about these complications, manageable through a prompt evaluation by the reference neurologist.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Transtornos dos Movimentos , Doença de Parkinson , Vacinação , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Carbidopa/uso terapêutico , Estimulação Encefálica Profunda , Combinação de Medicamentos , Humanos , Imunização Secundária/efeitos adversos , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Transtornos dos Movimentos/etiologia , Transtornos dos Movimentos/terapia , Doença de Parkinson/etiologia , Doença de Parkinson/terapia , Resultado do Tratamento , Vacinação/efeitos adversosRESUMO
BACKGROUND: Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective surgical treatment for advanced Parkinson's disease (PD). However, some patients still experience motor fluctuations or dyskinesia after STN-DBS. Safinamide is approved as add-on treatment to levodopa in fluctuating PD patients. In this study, we evaluated the effect of safinamide as adjunctive therapy in PD patients still experiencing motor fluctuations and dyskinesias after STN-DBS. METHODS: PD patients treated for at least 2 years with bilateral STN-DBST and with troublesome motor fluctuation and/or dyskinesias were examined by means of the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), the quality of life questionnaire Parkinson's Disease Questionnaire-8 (PDQ-8) and the Non-Motor Symptoms Scale (NMSS) at baseline (T0), after 1 month of treatment with safinamide 50 mg daily (T1) and after another month of treatment with safinamide 100 mg daily (T2). RESULTS: Twenty-nine PD patients were examined. An improvement of the MDS-UPDRS IV score (motor complications) was observed between T0 and T1, T0 and T2, and T1 and T2. The time spent in the OFF state, the functional impact and the complexity of motor fluctuations significantly improved between T0 and T1 and T0 and T2. The mean levodopa equivalent daily dose significantly decreased from T0 to T1 and from T0 to T2. Regarding non-motor symptoms, an improvement on mood and pain was observed. CONCLUSIONS: Safinamide seems to be an effective adjunctive treatment in PD patients treated with bilateral STN-DBS, leading to an improvement of motor complications, mood and pain.
Assuntos
Estimulação Encefálica Profunda , Discinesias , Doença de Parkinson , Núcleo Subtalâmico , Alanina/análogos & derivados , Benzilaminas , Estimulação Encefálica Profunda/efeitos adversos , Discinesias/etiologia , Humanos , Levodopa/uso terapêutico , Dor , Doença de Parkinson/tratamento farmacológico , Qualidade de Vida , Resultado do TratamentoRESUMO
PURPOSE: Tolcapone is an efficacious catechol-O-methyltransferase inhibitor for Parkinson's disease (PD). However, safety issues hampered its use in clinical practice. We aimed to provide evidence of safety and efficacy of tolcapone by a systematic literature review to support clinicians' choices in the use of an enlarging PD therapeutic armamentarium. METHODS: We searched PubMed for studies on PD patients treated with tolcapone, documenting the following outcomes: liver enzyme, adverse events (AEs), daily Off-time, levodopa daily dose, unified Parkinson's disease rating scale (UPDRS) part-III, quality of life (QoL), and non-motor symptoms. FAERS and EudraVigilance databases for suspected AEs were interrogated for potential additional cases of hepatotoxicity. RESULTS: Thirty-two studies were included, for a total of 4780 patients treated with tolcapone. Pertaining safety, 0.9% of patients showed liver enzyme elevation > 2. Over 23 years, we found 7 cases of severe liver injury related to tolcapone, 3 of which were fatal. All fatal cases did not follow the guidelines for liver function monitoring. FAERS and EudraVigilance database search yielded 61 reports of suspected liver AEs possibly related to tolcapone. Pertaining efficacy, the median reduction of hours/day spent in Off was 2.1 (range 1-3.2), of levodopa was 108.9 mg (1-251.5), of "On" UPDRS-III was 3.6 points (1.1-6.5). Most studies reported a significant improvement of QoL and non-motor symptoms. CONCLUSION: Literature data showed the absence of relevant safety concerns of tolcapone when strict adherence to hepatic function monitoring is respected. Given its high efficacy on motor fluctuations, tolcapone is probably an underutilized tool in the therapeutic PD armamentarium.
Assuntos
Antiparkinsonianos/uso terapêutico , Inibidores de Catecol O-Metiltransferase/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Tolcapona/uso terapêutico , Antiparkinsonianos/efeitos adversos , Inibidores de Catecol O-Metiltransferase/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Humanos , Levodopa/administração & dosagem , Testes de Função Hepática , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Tolcapona/efeitos adversosRESUMO
OBJECTIVES: To provide new insights into neurological manifestations of COVID-19. We describe a patient with mild COVID-19 associated with diplopia from right sixth cranial nerve palsy and early diffuse leukoencephalopathy, successfully treated with intravenous methylprednisolone. METHODS: The patient was evaluated for diplopia that occurred 1 day after the onset of fever, myalgia, and headache. A complete neurological workup, including neurological examination, cerebrospinal fluid (CSF) analysis with viral polymerase chain reaction (PCR), serum autoimmune encephalitis, and anti-nerve antibodies and brain magnetic resonance imaging (MRI), was performed. RESULTS: Clinical examination revealed incomplete right sixth cranial nerve palsy. Brain MRI showed diffuse confluent fluid-attenuated inversion recovery (FLAIR) hyperintense white matter abnormalities, while CSF analysis showed mild hyperproteinorrachia (61 mg/dL) without pleocytosis. The patients were treated with high-dose intravenous methylprednisolone with rapid improvement of neurological symptoms and resolution of CSF and MRI abnormalities. DISCUSSION: Our report shows that COVID-19 may predominantly present with neurological symptoms; furthermore, it argues the notion of leukoencephalopathy as a typical feature of a severe case of the disease. Mechanisms underpinning neurological symptoms in COVID-19 still need to be elucidated; nonetheless, early recognition and prompt management may ensure their improvement or even complete recovery and are therefore recommended.
Assuntos
Doenças do Nervo Abducente , COVID-19 , Leucoencefalopatias , Doenças do Nervo Abducente/tratamento farmacológico , Diplopia/tratamento farmacológico , Diplopia/etiologia , Humanos , Imageamento por Ressonância Magnética , SARS-CoV-2RESUMO
OBJECTIVE: Genetic subtypes of dystonia may respond differentially to deep brain stimulation of the globus pallidus pars interna (GPi DBS). We sought to compare GPi DBS outcomes among the most common monogenic dystonias. METHODS: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology guidelines. We searched PubMed for studies on genetically confirmed monogenic dystonia treated with GPi DBS documenting pre-surgical and post-surgical assessments using the Burke-Fahn-Marsden Dystonia Rating Scale Motor Score (BFMMS) and Burke-Fahn-Marsden Disability Score (BFMDS). We performed (i) meta-analysis for each gene mutation; (ii) weighted ordinary linear regression analyses to compare BFMMS and BFMDS outcomes between DYT-TOR1A and other monogenic dystonias, adjusting for age and disease duration and (iii) weighted linear regression analysis to estimate the effect of age, sex and disease duration on GPi DBS outcomes. Results were summarised with mean change and 95% CI. RESULTS: DYT-TOR1A (68%, 38.4 points; p<0.001), DYT-THAP1 (37% 14.5 points; p<0.001) and NBIA/DYT-PANK2 (27%, 21.4 points; p<0.001) improved in BFMMS; only DYT-TOR1A improved in BFMDS (69%, 9.7 points; p<0.001). Improvement in DYT-TOR1A was significantly greater than in DYT-THAP1 (BFMMS -31%), NBIA/DYT-PANK2 (BFMMS -35%; BFMDS -53%) and CHOR/DYT-ADCY5 (BFMMS -36%; BFMDS -42%). Worse motor outcomes were associated with longer dystonia duration and older age at dystonia onset in DYT-TOR1A, longer dystonia duration in DYT/PARK-TAF1 and younger age at dystonia onset in DYT-SGCE. CONCLUSIONS: GPi DBS outcomes vary across monogenic dystonias. These data serve to inform patient selection and prognostic counselling.
Assuntos
Estimulação Encefálica Profunda , Distonia/terapia , Distúrbios Distônicos/terapia , Globo Pálido , Idade de Início , Distonia/genética , Distonia/fisiopatologia , Distúrbios Distônicos/genética , Distúrbios Distônicos/fisiopatologia , Humanos , Terapêutica , Fatores de Tempo , Resultado do TratamentoRESUMO
Gait and posture parameters of ten advanced Parkinson's disease (PD) patients were assessed before and after starting levodopa-carbidopa intestinal gel (LCIG) treatment by means of both objective video analysis and clinical assessment. After 3 years of treatment, gait and posture remained stable. A slower gait velocity at baseline significantly correlates with a higher axial and motor severity at follow-up. This pilot study suggests that validated video analysis software may support the clinical assessment of axial signs in PD patients who are candidates for device-aided therapies.
Assuntos
Carbidopa , Doença de Parkinson , Antiparkinsonianos , Combinação de Medicamentos , Marcha , Géis , Humanos , Levodopa , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico , Projetos Piloto , PosturaRESUMO
Axial postural abnormalities (PA) are frequent, highly disabling, and drug-refractory motor complications affecting patients with Parkinson's disease (PD) or atypical parkinsonism. Over the past few years, advances have been reached across diagnosis, assessment, and pathophysiological mechanisms of PA. Nonetheless, their management remains a challenge, and these disturbances are generally overlooked by healthcare professionals, potentially resulting in their worsening and impact on patients' disabilities. From shared consensus-based assessment and diagnostic criteria, PA calls for interdisciplinary management based on the complexity and multifactorial pathogenesis. In this context, we conducted a systematic literature review to analyze the available pharmacological and non-pharmacological treatment options for PA in PD according to the new expert-based classification of axial PA in Parkinsonism. Different multidisciplinary approaches, including dopaminergic therapy adjustment, physiotherapy, botulinum toxin injection, and deep brain stimulation, can improve PA depending on its type and severity. An early, interdisciplinary approach is recommended in PD patients to manage PA.
RESUMO
INTRODUCTION: Gaucher disease (GD) is classically divided into three types, based on the presence or absence of neurological signs and symptoms. However, presentation can be highly variable in adulthood, and this aspect has not been adequately addressed in the literature so far. We performed a systematic literature review to analyze the entire spectrum of neurological manifestations in adult patients previously classified as GD type I, II, or III, evaluating the role of variants in different neurological manifestations. METHODS: We searched databases for studies reporting clinical data of adult GD patients (age ≥ 18). Data extraction included GD types, GBA1 variants, age at disease onset and diagnosis, duration of GD, and age at onset and type of neurological symptoms reported. RESULTS: Among 4190 GD patients from 85 studies, 555 exhibited neurological symptoms in adulthood. The median age at evaluation was 46.8 years (IQR 26.5), age at neurological symptoms onset was 44 years (IQR 35.1), and age at GD clinical onset was 23 years (IQR 23.4). Parkinsonism, including Parkinson's disease and Lewy Body dementia, was the most reported neurological manifestation. Other symptoms and signs encompassed oculomotor abnormalities, peripheral neuropathy, seizures, myoclonus, and cerebellar, cognitive and psychiatric symptoms. The genotype N370S/N370S mostly presented with Parkinsonism and the L444P variant with severe and earlier neurological symptoms. CONCLUSION: The findings of this systematic review highlight: (1) the relevance of a comprehensive neurological assessment in GD patients, and (2) the importance of considering possible undiagnosed GD in adult patients with mild systemic symptoms presenting unexplained neurological symptoms.
Assuntos
Doença de Gaucher , Doenças do Sistema Nervoso , Humanos , Doença de Gaucher/complicações , Doença de Gaucher/genética , Doença de Gaucher/fisiopatologia , Doenças do Sistema Nervoso/etiologia , AdultoRESUMO
Axial postural abnormalities (APAs), characterized by their frequency, disabling nature, and resistance to pharmacological treatments, significantly impact Parkinson's disease and atypical Parkinsonism patients. Despite advancements in diagnosing, assessing, and understanding their pathophysiology, managing these complications remains a significant challenge. Often underestimated by healthcare professionals, these disturbances can exacerbate disability. This systematic review assesses botulinum toxin treatments' effectiveness, alone and with rehabilitation, in addressing APAs in Parkinson's disease, utilizing MEDLINE (PubMed), Web of Science, and SCOPUS databases for source material. Of the 1087 records retrieved, 16 met the selection criteria. Most research has focused on botulinum toxin (BoNT) as the primary treatment for camptocormia and Pisa syndrome, utilizing mostly observational methods. Despite dose and injection site variations, a common strategy was using electromyography-guided injections, occasionally enhanced with ultrasound. Patients with Pisa syndrome notably saw consistent improvements in APAs and pain. However, studies on the combined effects of botulinum toxin and rehabilitation are limited, and antecollis is significantly under-researched. These findings recommend precise BoNT injections into hyperactive muscles in well-selected patients by skilled clinicians, avoiding compensatory muscles, and underscore the necessity of early rehabilitation. Rehabilitation is crucial in a multidisciplinary approach to managing APAs, highlighting the importance of a multidisciplinary team of experts.
Assuntos
Toxinas Botulínicas , Doença de Parkinson , Humanos , Doença de Parkinson/tratamento farmacológico , Toxinas Botulínicas/uso terapêutico , Fármacos Neuromusculares/uso terapêutico , Curvaturas da Coluna Vertebral/tratamento farmacológico , PosturaRESUMO
BACKGROUND: Dyskinesias and freezing of gait are episodic disorders in Parkinson's disease, characterized by a fluctuating and unpredictable nature. This cross-sectional study aims to objectively monitor Parkinsonian patients experiencing dyskinesias and/or freezing of gait during activities of daily living and assess possible changes in spatiotemporal gait parameters. METHODS: Seventy-one patients with Parkinson's disease (40 with dyskinesias and 33 with freezing of gait) were continuously monitored at home for a minimum of 5 days using a single wearable sensor. Dedicated machine-learning algorithms were used to categorize patients based on the occurrence of dyskinesias and freezing of gait. Additionally, specific spatiotemporal gait parameters were compared among patients with and without dyskinesias and/or freezing of gait. RESULTS: The wearable sensor algorithms accurately classified patients with and without dyskinesias as well as those with and without freezing of gait based on the recorded dyskinesias and freezing of gait episodes. Standard spatiotemporal gait parameters did not differ significantly between patients with and without dyskinesias or freezing of gait. Both the time spent with dyskinesias and the number of freezing of gait episodes positively correlated with the disease severity and medication dosage. CONCLUSIONS: A single inertial wearable sensor shows promise in monitoring complex, episodic movement patterns, such as dyskinesias and freezing of gait, during daily activities. This approach may help implement targeted therapeutic and preventive strategies for Parkinson's disease.
RESUMO
Background: Gait issues, including reduced speed, stride length and freezing of gait (FoG), are disabling in advanced phases of Parkinson's disease (PD), and their treatment is challenging. Levodopa/carbidopa intestinal gel (LCIG) can improve these symptoms in PD patients with suboptimal control of motor fluctuations, but it is unclear if continuous dopaminergic stimulation can further improve gait issues, independently from reducing Off-time. Objective: To analyze before (T0) and after 3 (T1) and 6 (T2) months of LCIG initiation: a) the objective improvement of gait and balance; b) the improvement of FoG severity; c) the improvement of motor complications and their correlation with changes in gait parameters and FoG severity. Methods: This prospective, longitudinal 6-months study analyzed quantitative gait parameters using wearable inertial sensors, FoG with the New Freezing of Gait Questionnaire (NFoG-Q), and motor complications, as per the MDS-UPDRS part IV scores. Results: Gait speed and stride length increased and duration of Timed up and Go and of sit-to-stand transition was significantly reduced comparing T0 with T2, but not between T0-T1. NFoG-Q score decreased significantly from 19.3±4.6 (T0) to 11.8±7.9 (T1) and 8.4±7.6 (T2) (T1-T0 pâ=â0.018; T2-T0 pâ<â0.001). Improvement of MDS-UPDRS-IV (T0-T2, pâ=â0.002, T0-T1 pâ=â0.024) was not correlated with improvement of gait parameters and NFoG-Q from T0 to T2. LEDD did not change significantly after LCIG initiation. Conclusion: Continuous dopaminergic stimulation provided by LCIG infusion progressively ameliorates gait and alleviates FoG in PD patients over time, independently from improvement of motor fluctuations and without increase of daily dosage of dopaminergic therapy.
Assuntos
Antiparkinsonianos , Carbidopa , Combinação de Medicamentos , Transtornos Neurológicos da Marcha , Géis , Levodopa , Doença de Parkinson , Humanos , Levodopa/administração & dosagem , Levodopa/farmacologia , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/complicações , Doença de Parkinson/fisiopatologia , Masculino , Idoso , Feminino , Pessoa de Meia-Idade , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/tratamento farmacológico , Transtornos Neurológicos da Marcha/fisiopatologia , Estudos Longitudinais , Carbidopa/administração & dosagem , Carbidopa/farmacologia , Estudos Prospectivos , Antiparkinsonianos/administração & dosagem , Antiparkinsonianos/farmacologiaRESUMO
BACKGROUND: Sleep disorders negatively impact quality of life in Parkinson's disease (PD), yet the role of antiparkinsonian drugs on sleep quality is still unclear. We aimed to explore the correlation between sleep dysfunction and dopaminergic therapy in a large cohort of advanced PD patients. METHODS: Patients consecutively evaluated for device-aided therapies eligibility were evaluated by means of the PD Sleep Scale (PDSS-2; score ≥ 18 indicates poor sleep quality), and the Epworth Sleepiness Scale (ESS score ≥ 10 indicates excessive daytime sleepiness-EDS). Binary logistic regression analysis, adjusting for age, sex, disease duration, motor impairment, and sleep drugs, was employed to evaluate the association between dopaminergic therapy and PDSS-2 and ESS scores. Analysis of covariance assessed differences in PDSS-2 and ESS scores between patients without DA, and between patients treated with low or high doses of DA (cut-off: DA-LEDD = 180 mg). RESULTS: In a cohort of 281 patients, 66.2% reported poor sleep quality, and 34.5% reported EDS. DA treatment demonstrated twofold lower odds of reporting relevant sleep disturbances (OR 0.498; p = 0.035), while DA-LEDD, levodopa-LEDD, total LEDD, and extended-release levodopa were not associated with disturbed sleep. EDS was not influenced by dopaminergic therapy. Patients with DA intake reported significant lower PDSS-2 total score (p = 0.027) and "motor symptoms at night" domain score (p = 0.044). Patients with higher doses of DA showed lower PDSS-2 total score (p = 0.043). CONCLUSION: Our study highlights the positive influence of DA add-on treatment on sleep quality in this group of advanced fluctuating PD patients.
Assuntos
Antiparkinsonianos , Dopaminérgicos , Doença de Parkinson , Qualidade do Sono , Transtornos do Sono-Vigília , Humanos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/complicações , Doença de Parkinson/fisiopatologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Dopaminérgicos/administração & dosagem , Dopaminérgicos/farmacologia , Antiparkinsonianos/administração & dosagem , Antiparkinsonianos/uso terapêutico , Transtornos do Sono-Vigília/etiologia , Transtornos do Sono-Vigília/tratamento farmacológico , Levodopa/administração & dosagem , Levodopa/farmacologia , Estudos de Coortes , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Non-motor symptoms and non-motor fluctuations (NMF) in Parkinson's disease (PD) strongly affect health-related quality of life (HRQoL) and disability. The impact of deep brain stimulation (DBS) on NMF remains an area of uncertainty. The aim is to evaluate the impact of DBS on NMF, using the recently validated Non-Motor Fluctuation Assessment (NoMoFa), and to explore the correlation between NMF and motor symptoms, motor complications (MC), and HRQoL post-surgical improvement. METHODS: We prospectively evaluated consecutive patients undergoing subthalamic DBS (STN-DBS), at baseline and 6-months after surgery. Assessments included the NoMoFa questionnaire, the MDS-sponsored Unified Parkinson's Disease Rating Scale, and the 39-Item Parkinson's Disease Questionnaire. Pre- and post-surgical NoMoFa scores were compared using the Wilcoxon Signed rank-test. Linear regression analysis evaluated: a) the correlation between NoMoFa scores, motor and MC improvement, correcting for age, disease duration, and dopaminergic therapy reduction; b) the correlation between HRQoL and NMF improvement, correcting for age, disease duration, motor and MC improvement. RESULTS: Twenty patients were evaluated. Total NMF score significantly improved (44.6 %, [IQR = 18.3-100]; p = 0.022), particularly in Off condition (52.0 %, [IQR = 25.4-100]; p = 0.009); we observed strong correlation between NMF and MC improvement (Beta = 0.728; p = 0.006), mainly driven by the mitigation of unpredictable Off (Beta = 0.905; p < 0.001). Even after adjusting for potential confounders, the reduction of NMF independently correlated with increased HRQoL (Beta = 0.714; p = 0.010). CONCLUSIONS: STN-DBS demonstrated strong beneficial effect on NMF, resulting in significant improvement of HRQoL. This underlines the importance of recognizing NMF as a significant factor to be considered in the selection of patients eligible for STN-DBS.