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.

Patients and Health Professional's Perspective of Functional Mobility in Parkinson's Disease.

Background: Functional mobility (FM) is the person's ability to move to accomplish daily living tasks and activities. FM limitations are common in Parkinson's disease, increase with disease progression, and can be highly disabling. Although several studies in Parkinson's disease (PD) field use this concept, only recently, a formal definition has been proposed. Objective: We aimed to explore patient's and health professional's perspectives of FM in PD. Methods: A focus group methodology has been used. Four focus groups, with a total of 10 patients and 10 health professionals, were performed. Six patients were early stage and four advanced stage. The health professional's group was composed of five neurologists and five physiotherapists. The suitability of the new concept, the impact of FM limitations in PD patient's daily routine, and the potential benefit of walking aids have been discussed. Results: All participants were able to provide a spontaneous definition of FM, matching with the proposed concept. All agreed that PD affects patient's FM, increasing the limitations with disease progression, and with the existence of a serious prejudice with walking aids that hinders its use. Early-stage patient's perspective seems to be more in line with neurologist's perspective, while the views of advanced-stage patients were closer to physiotherapist's views. Conclusion: FM concept was considered as intuitive and useful. FM limitations have an important physical and social impact in the advanced stage of the disease. Although patients and health professionals acknowledge walking aid's benefit improving patient's FM, the prejudice associated with this type of tools limits its recommendation and use.

Disability in Activities of Daily Living and Severity of Dyskinesias Determine the Handicap of Parkinson's Disease Patients in Advanced Stage Selected to DBS.

BACKGROUND: There is scarce data on the level of handicap in Parkinson's disease (PD) and none in advanced stage PD. OBJECTIVE: To assess the handicap in advanced stage PD patients with disabling levodopa-induced motor complications selected to deep brain stimulation (DBS). METHODS: Data was prospectively recorded during routine evaluation for DBS. Handicap was measured using London Handicap Scale (LHS) (0 = maximal handicap; 1 = no handicap). Disease severity was evaluated using the Hoehn & Yahr scale and the UPDRS/MDS-UPDRS, during off and on after a supra-maximal dose of levodopa. Schwab and England Scale (S&E) was scored in off and on. Dyskinesias were scored using the modified Abnormal Involuntary Movement Scale (mAIMS). Results concern cross-sectional assessment before DBS. RESULTS: 100 PD patients (mean age 61 (±7.6); mean disease duration 12.20 (±4.6) years) were included. Median score of motor MDS-UPDRS was 54 in off and 25 in on. Mean total LHS score was 0.56 (±0.14). Patients were handicapped in several domains with a wide range of severity. Physical Independence and Social Integration were the most affected domains. Determinants of total LHS score were MDS-UPDRS part II off (ß= -0.271; p = 0.020), S&E on (ß= 0.264; p = 0.005) and off (ß= 0.226; p = 0.020), and mAIMS on (ß= -0.183; p = 0.042) scores (R2  = 29.6%). CONCLUSIONS: We were able to use handicap to measure overall health condition in advanced stage PD. Patients were moderately to highly handicapped and this was strongly determined by disability in ADL and dyskinesias. Change in handicap may be a good patient-centred outcome to assess efficiency of DBS.

Familial SUNCT in mother and son.

BACKGROUND: Trigeminal autonomic cephalalgias comprise a heterogeneous group of lateralized headaches associated with ipsilateral autonomic symptoms. They are usually localized within the territory of one or more rami of the trigeminal nerve, but may be localized outside its cutaneous territory. Although these headaches are considered primary disorders, the evidence supporting their genetic nature is lacking, particularly concerning their neuralgic forms, with the exception of a familial case described partly based on a historical account. CASE REPORTS: We report on a mother and son with episodic, short-lasting, intense, paroxysmal headaches, with the same localization in the left retroauricular region, associated with prominent conjunctival injection and tearing, which are consistent with the diagnosis of SUNCT (short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing). DISCUSSION: These cases corroborate the existence of hereditary forms of this disorder, thus supporting its primary nature.

Time- and frequency-domain parameters of heart rate variability and sympathetic skin response in Parkinson's disease.

The autonomic nervous system (ANS) is regularly affected in Parkinson's disease (PD). Information on autonomic dysfunction can be derived from e.g. altered heart rate variability (HRV) and sympathetic skin response (SSR). Such parameters can be quantified easily and measured repeatedly which might be helpful for evaluating disease progression and therapeutic outcome. In this 2-center study, HRV and SSR of 45 PD patients and 26 controls were recorded. HRV was measured during supine metronomic breathing and analyzed in time- and frequency-domains. SSR was evoked by repetitive auditory stimulation. Various ANS parameters were compared (1) between patients and healthy controls, (2) to clinical scales (Unified Parkinson's disease rating scale, Mini-Mental State Examination, Becks Depression Inventory), and (3) to disease duration. Root mean square of successive differences (RMSSD) and low frequency/high frequency (LF/HF) ratio differed significantly between PD and controls. Both, HRV and SSR parameters showed low or no association with clinical scores. Time-domain parameters tended to be affected already at early PD stages but did not consistently change with longer disease duration. In contrast, frequency-domain parameters were not altered in early PD phases but tended to be lower (LF, LF/HF ratio), respectively higher (HF) with increasing disease duration. This report confirms previous results of altered ANS parameters in PD. In addition, it suggests that (1) these ANS parameters are not relevantly associated with motor, behavioral, and cognitive changes in PD, (2) time-domain parameters are useful for the assessment of early PD, and (3) frequency-domain parameters are more closely associated with disease duration.

Comprehensive LRRK2 and GBA screening in Portuguese patients with Parkinson's disease: identification of a new family with the LRRK2 p.Arg1441His mutation and novel missense variants.

Mutations in the LRRK2 and GBA genes are increasingly recognized as frequent determinants of familial and sporadic Parkinson's disease (PD). However, for several populations, accurate data on the prevalence and types of mutations are not available, because previous studies have not investigated the complete coding regions of these genes in large samples. We studied 312 PD patients ascertained at a single centre in Lisbon, Portugal. In 61 patients, with familial PD, we sequenced the entire open reading frames and exon-intron boundaries of LRRK2 and GBA. In LRRK2, we identified ten heterozygous p.Gly2019Ser (16.4%), and two heterozygous p.Arg1441His carriers (3.3%); furthermore, six patients each carried a novel LRRK2 heterozygous variant (five coding and one 3'-UTR variants) of undetermined pathogenic role. Segregation of the p.Arg1441His mutation with PD was observed in the families of both carriers. None of these variants were identified in 138 healthy controls. Screening of GBA revealed no mutations. In the remaining 251 PD patients (25 familial and 226 sporadic) we found ten additional carriers of the heterozygous p.Gly2019Ser and no carriers of the other mutations. Thus, the p.Gly2019Ser mutation was detected in a total number of 20 carriers out of 312 patients (6.4%), including twelve familial (14%) and eight sporadic patients (3.5%). This comprehensive study confirms that p.Gly2019Ser is the most important genetic cause of PD known so far in Portugal and supports the contention that p.Arg1441His is also a PD-causing mutation. These findings have relevance for the genetic testing and counseling of PD patients in this population.

Orofacial apraxia in motor neuron disease.

INTRODUCTION: Cognitive and behavioral impairments are considered to occur frequently in amyotrophic lateral sclerosis/motor neuron disease (MND). Rarely, apraxia has been reported in MND. Orofacial, or buccofacial, apraxia is characterized by a loss of voluntary control of facial, lingual, pharyngeal and masticatory muscles in the presence of preserved reflexive and automatic functions of the same muscles. METHODS: We report a patient with MND who presented with spastic dysarthria and asymmetric orofacial apraxia. She progressed to frontotemporal dementia (FTD). RESULTS: Clinical and neurophysiological examinations were suggestive of bulbar-onset MND-FTD. Tractography showed a reduction of fractional anisotropy in the centrum semiovale, corona radiata, corticomedullary pathway and inferior aspect of the medulla; the changes were more severe on the left side. To our knowledge, this is the first report of an asymmetric presentation of an apraxic syndrome in MND-FTD.

Myeloradiculopathy associated to Schistosoma mansoni.

Neuroschistosomiasis caused by Schistosoma mansoni (Sm) is a rare and severe condition potentially leading to permanent neurological deficit. An 18-year-old Brazilian female was admitted due to a severe conus medullaris and cauda equina syndrome. MRI of thoracic/lumbar spine showed an expanded conus medullaris with patchy gadolinium-enhancement, needle electromyography revealed acute bilateral radiculopathy (L5-S1-S2), cerebrospinal fluid (CSF) showed lymphocytosis and increased proteins and lesion' surgical biopsy documented a lymphocyte infiltrate. Immunodiagnosis with cercariae hullen reaction using Sm cercariae in CSF and serum and immunoelectrodiffusion for circulating antigens detection using anti-Sm antibodies were positive. No schistosoma parasites were found. The patient was treated with praziquantel and corticotherapy for 6 months. At 1 month, partial clinical improvement was noticed, and MRI showed a normal size conus medullaris. At 6 months, there was complete clinical recovery. This case shows that a severe neurological deficit by Sm may have a clinical full recovery after treatment.