Long-term follow-up of subthalamic nucleus deep brain stimulation in patients with Parkinson's disease: An analysis of survival and disability milestones.

BACKGROUND: Data on the long-term survival and incidence of disability milestones after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) is limited. OBJECTIVES: To estimate mortality and assess the frequency/time-to-development of disability milestones (falls, freezing, hallucinations, dementia, and institutionalization) among PD patients post STN-DBS. METHODS: A longitudinal retrospective study of patients undergoing STN-DBS. For mortality, Cox proportional hazards regression analysis was performed. For disease milestones, competing risk analyses were performed and cumulative incidence functions reported. The strength of association between baselines features and event occurrence was calculated based on adjusted hazard ratios. RESULTS: The overall mortality for the 109 patients was 16 % (62.1 ± 21.3 months after surgery). Falls (73 %) and freezing (47 %) were both the earliest (40.4 ± 25.4 and 39.6 ± 28.4 months, respectively) and most frequent milestones. Dementia (34 %) and hallucinations (32 %) soon followed (56.2 ± 21.2 and mean 60.0 ± 20.7 months after surgery, respectively). Higher ADL scores in the OFF state and higher age at surgery were associated with falls, freezing, dementia and institutionalization. CONCLUSIONS: Long-term mortality rate is low after STN-DBS. Disease milestones occur later during the disease course, with motor milestones appearing first and at a higher frequency than cognitive ones.

Molecular Characterization of Portuguese Patients with Hereditary Cerebellar Ataxia.

Hereditary cerebellar ataxia (HCA) comprises a clinical and genetic heterogeneous group of neurodegenerative disorders characterized by incoordination of movement, speech, and unsteady gait. In this study, we performed whole-exome sequencing (WES) in 19 families with HCA and presumed autosomal recessive (AR) inheritance, to identify the causal genes. A phenotypic classification was performed, considering the main clinical syndromes: spastic ataxia, ataxia and neuropathy, ataxia and oculomotor apraxia (AOA), ataxia and dystonia, and ataxia with cognitive impairment. The most frequent causal genes were associated with spastic ataxia (SACS and KIF1C) and with ataxia and neuropathy or AOA (PNKP). We also identified three families with autosomal dominant (AD) forms arising from de novo variants in KIF1A, CACNA1A, or ATP1A3, reinforcing the importance of differential diagnosis (AR vs. AD forms) in families with only one affected member. Moreover, 10 novel causal-variants were identified, and the detrimental effect of two splice-site variants confirmed through functional assays. Finally, by reviewing the molecular mechanisms, we speculated that regulation of cytoskeleton function might be impaired in spastic ataxia, whereas DNA repair is clearly associated with AOA. In conclusion, our study provided a genetic diagnosis for HCA families and proposed common molecular pathways underlying cerebellar neurodegeneration.

Psychosis in Huntington´s Disease. a rare and Under-Investigated Psychiatric Manifestation / Psychosis in Huntington's Disease: uma manifestação psiquiátrica rara e pouco investigada

Introduction: Psychotic symptoms are among the least prevalent and under-investigated psychiatric manifestations (PM) of Huntington's disease (HD). Case report: We herein report a case of a 31-year-old male patient who presented PM with a predominance of negative symptoms, without any significant abnormal movement. HD was diagnosed based on positive DNA analysis and family history. HD imposes longitudinal follow-up through a multidisciplinary approach in order to improve the quality of life and prognosis. Conclusion: This case report highlights the importance of comprehending the PM in the initial presentation of HD so that the diagnosis is not delayed until the onset of motor symptoms.

Introdução: Os sintomas psicóticos estão entre as manifestações psiquiátricas (MP) menos prevalentes e pouco investigadas da doença de Huntington (DH). Relado de caso: Relatamos o caso de um paciente do sexo masculino, 31 anos, que apresentou MP com predomínio de sintomas negativos, sem qualquer movimento anormal significativo. A DH foi diagnosticada com base em uma análise de DNA positiva e na história familiar. A DH impõe um acompanhamento longitudinal por meio de uma abordagem multidisciplinar, a fim de melhorar a qualidade de vida e o prognóstico. Conclusão: Este relato de caso destaca a importância da compreensão das MPs na apresentação inicial da DH, para que o diagnóstico não seja atrasado até ao aparecimento dos sintomas motores

Acute response of non-motor symptoms to subthalamic deep brain stimulation in Parkinson's disease.

BACKGROUND: Subthalamic deep brain stimulation (STN-DBS) is an established treatment for the motor complications of Parkinson's disease (PD) and may have beneficial effects on non-motor symptoms (NMS). However, the acute effect of STN stimulation on NMS has only been explored in small PD cohorts with short post-surgical follow-up. OBJECTIVE: To study NMS response to an acute stimulation challenge in an STN-DBS PD population with a medium/long-term post-surgical follow-up. METHODS: 32 STN-DBS PD patients were tested twice (MED OFF/STIM OFF and MED OFF/STIM ON). MDS-UPDRS-III, blood pressure (BP) assessment, a visual analogue scale for pain and fatigue and State Trait Anxiety Scale score were evaluated during both stimulation conditions. NMS were assessed with MDS-UPDRS-I, Non-Motor Symptoms Scale, Geriatric Depression Scale and the Neuropsychiatric Inventory scale. RESULTS: Mean (SD) age was 62.5 (±13.3) years, mean disease duration 18.7 (±5.1) years, mean post-surgical follow-up 4.6 (±1.3) years, and the mean reduction of levodopa equivalent daily dose after surgery was 58.9% (±25.4%). Mean (SD) motor response to stimulation was 40% (15%). STN stimulation significantly improved anxiety (mean 18% ± 19%, P < 0.005) and fatigue (mean 25% ± 51%; P < 0.05), while pain, although improved did not reach statistical significance. With stimulation ON, BP significantly decreased during orthostatism (P < 0.05) and there was a significant increase in asymptomatic orthostatic hypotension (P < 0.05). CONCLUSIONS: Acute STN stimulation improves anxiety and fatigue but decreases orthostatic BP in PD, several years after surgery. These effects should be considered when assessing long-term effect of DBS.

STN-DBS does not change emotion recognition in advanced Parkinson's disease.

UNLABELLED: Deep brain stimulation of the subthalamic nuclei (STN-DBS) for the treatment of levodopa-induced motor complications in advanced Parkinson's disease (APD) has been associated with neuropsychiatric disorders. It has been suggested that a postoperative decline in visual emotion recognition is responsible for those adverse events, although there is also evidence that emotional processing deficits can be present before surgery. The aim of the present study is to compare the ability to recognize emotions before and one year after surgery in APD. METHODS: Consecutively operated APD patients were tested pre-operatively and one year after STN-DBS by the Comprehensive Affect Testing System (CATS), which evaluates visual recognition of 7 basic emotions (happiness, sadness, anger, fear, surprise, disgust and neutral) on facial expressions and 4 emotions on prosody (happiness, sadness, anger and fear). RESULTS: In a sample of 30 patients 6 had depression or apathy at baseline that significantly increased to 14 post-surgery. There were no significant changes in the tests of identity discrimination, discrimination of emotional faces, naming of emotional faces, recognition of emotional prosody, and naming of emotional prosody after STN-DBS. The results of emotion tests could not predict the development of the neuropsychiatric symptoms. DISCUSSION: This study does not support the hypothesis of an acquired change in emotion recognition, either in faces or in prosody, after STN-DBS in APD patients. Neuropsychiatric symptoms appearing after STN-DBS should not be attributed to new deficits in emotional recognition.

Skin cancers and precancerous lesions in Parkinson's disease patients.

Our objective was to evaluate the frequency of neoplastic and preneoplastic skin lesions in Parkinson's disease (PD) patients when compared with an aged-matched population. We performed a cross-sectional survey in PD patients and in an age-matched control group. Patients and controls were examined by a movement disorder specialist and a dermatologist. 150 PD patients and 146 controls were included. Thirty-five PD patients (23.3%) presented skin lesions that could be classified as neoplastic or preneoplastic vs. 20 subjects in the control group (13.7%) (OR 95%, CI 1.92 [1.05, 3.51]). However, this difference lost statistical significance when adjusted for gender (recruitment of controls was matched just for age with an over representation of males in the PD group). Twenty-nine PD patients (19%) presented actinic keratosis and basal cell carcinoma was diagnosed in 4 patients (3%). Although nonconclusive, our results are in agreement with previous studies suggesting an increased risk of skin cancer in PD patients. The frequency of actinic keratosis in PD patients and the associated risk to develop melanoma recommends its screening in future epidemiological studies.