Serena Angrisano

Transient effects of 80 Hz stimulation on gait in STN DBS treated PD patients: A 15 months follow-up study

BACKGROUND Subthalamic nucleus deep brain stimulation (STN DBS) is an effective therapeutic option for advanced Parkinsons disease (PD). Nevertheless, some patients develop gait disturbances despite a persistent improvement of PD segmental symptoms. Recent studies reported that stimulation of STN with low frequencies produced a positive effect on gait disorders and freezing episodes. OBJECTIVE To evaluate the effects of 80 Hz stimulation frequency on gait in PD patients undergoing STN DBS and to determine whether such effects are maintained over time. METHODS We evaluated 11 STN DBS treated PD patients who had developed gait impairment several years after surgery. Gait was assessed by means of the Stand-Walk-Sit (SWS) test. Motor symptoms and activities of daily living were evaluated through the Unified PD Rating Scale (UPDRS). The stimulation frequency was switched from 130 Hz to 80 Hz, adapting the voltage to maintain the same total delivered energy. Patients were assessed at baseline and 3 hours after switching the stimulation frequency to 80 Hz. Follow-up evaluations were carried out after 1, 5, and 15 months. The clinical global improvement scale was rated at every follow-up visit. RESULTS A significant improvement of gait (SWS test) was evident immediately after switching the stimulation frequency to 80 Hz, with no deterioration of PD segmental symptoms. However, gait improvement was no longer detectable by the SWS test at follow-up evaluations 1, 5, and 15 months later. Three patients were switched back to 130 Hz because of unsatisfactory control of motor symptoms. Of the eight patients maintained at 80 Hz up to 15 months, five showed a global improvement and three showed no change. CONCLUSIONS Stimulation frequency at 80 Hz has an immediate positive effect on gait in STN DBS treated patients; however, the objective gait improvement is not maintained over time, limiting the use of this frequency modulation strategy in the clinical setting.

Levodopa/carbidopa intestinal gel infusion in advanced Parkinson's disease: a 7-year experience

Levodopa/carbidopa intestinal gel (LCIG) infusion is nowadays becoming an established therapeutic option for advanced Parkinsons disease (PD) patients with fluctuating symptoms unresponsive to conventional oral treatment. As the implementation of LCIG therapy is increasing, there is a need for safety and efficacy data from current clinical practice.

Neuropsychological changes 1-year after subthalamic DBS in PD patients: A prospective controlled study ☆

OBJECTIVE This study aimed at investigating the neuropsychological effect of DBS of the Subthalamic Nucleus in patients with advanced Parkinsons disease (PD). METHODS A standardized neuropsychological test battery, assessing reasoning, memory and executive functions, was administered to 27 PD patients who underwent DBS-STN (DBS group) and to a matched control group of 31 PD patients under optimal medical treatment (MED group). Patients were evaluated at baseline and at the end of 1 year. RESULTS Change score analysis (T1 minus T0 scores) demonstrated a significant decline in phonemic verbal fluency in the DBS group compared with the MED group (p < 0.005), while there were no significant changes between the two groups for the other cognitive tests. Single cases analysis by means of multivariate normative comparisons revealed that 4 out of 27 DBS patients (15%) showed cognitive deterioration one year post surgery. These patients were significantly more compromised from a motor standpoint (UPDRS, section III) than the 23 DBS PD patients who had no cognitive decline post surgery. CONCLUSION Results of this prospective controlled-study showed that phonemic verbal fluency declined one year after DBS-STN, while the other cognitive domains did not change significantly. Nevertheless, single case analysis highlighted the fact that a subgroup comprising 15% of DBS-STN patients (4/27) showed significant cognitive decline 1 year after surgery.

Comparison of subthalamic nucleus deep brain stimulation and Duodopa in the treatment of advanced Parkinson's disease

Subthalamic nucleus deep brain stimulation (STN‐DBS) and levodopa/carbidopa enteral (Duodopa) infusion are two effective therapeutic options for the treatment of advanced Parkinsons disease (PD).

Sleep improvement with levodopa/ carbidopa intestinal gel infusion in Parkinson disease

Sleep disorders are common in patients with advanced Parkinsons disease (PD). Nocturnal akinesia and sleep fragmentation frequently coexist with daytime sleepiness, influencing daytime functioning. Levodopa/carbidopa intestinal gel (LCIG) infusion has been shown to improve motor complications in advanced PD, and preliminary findings suggest that sleep might improve following LCIG infusion.

Prospective assessment of peripheral neuropathy in Duodopa‐treated parkinsonian patients

Although peripheral neuropathies (PN) have been described in patients with Parkinsons disease (PD) treated with oral dopaminergic therapies, anecdotal reports of subacute severe PN have been reported during treatment with enteral levodopa/carbidopa infusion (Duodopa).

Medical therapy and subthalamic deep brain stimulation in advanced Parkinson's disease: a different long-term outcome?

Objectives Few clinical trials reported the comparative short-term efficacy of subthalamic nucleus deep brain stimulation (STN-DBS) versus medical therapy in advanced Parkinsons disease (PD). However, the comparative efficacy, safety and the potential disease-modifying effect of these treatments have not been investigated over a longer follow-up period. Methods In this study, we organised a ‘retrospective control group’ to compare medical and surgical therapies over a long-term period. We assessed a group of PD patients suitable for STN-DBS but successively treated with medical therapies for reasons not related to PD, and a group of similar consecutive STN-DBS patients. We thus obtained two groups comparable at baseline, which were re-evaluated after an average follow-up of 6 years (range 4–11). Results Patients treated with STN-DBS showed a long-lasting superior clinical efficacy on motor fluctuations, with a significant reduction in the average percentage of the waking day spent in ‘OFF’ and in the duration and disability of dyskinesia. Moreover, operated patients showed a better outcome in the activities of daily living in ‘Medication-OFF’ condition. On the other hand, a similar progression of motor score and cognitive/behavioural alterations was observed between the two groups, apart from phonemic verbal fluency, which significantly worsened in STN-DBS patients. Conclusions To our knowledge, this is the first long-term comparison between medical and surgical therapies; a superior efficacy of STN-DBS was observed on motor disability, while no significant differences were observed in the progression of motor symptoms and, apart from phonemic verbal fluency, of neuropsychological alterations.

80 Hz versus 130 Hz subthalamic nucleus deep brain stimulation: Effects on involuntary movements

BACKGROUND Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) represents a valid therapeutic option for advanced Parkinsons disease (PD), leading to a significant amelioration of motor fluctuations and levodopa-induced involuntary movements (IM). This study address the issue of whether stimulation frequency may influence the control of IM in STN-DBS treated patients, comparing the effects of 80 Hz and 130 Hz STN-DBS frequencies in 10 parkinsonian patients with residual IM (dyskinesia in 6 cases and dystonia in 4 cases). METHODS Patients were evaluated by means of the Rush Dyskinesias Rating Scale (blinded-video analysis) and Unified Parkinsons Disease Rating Scale at 4 different time-points: baseline, shortly after the switch of stimulation frequency from 130 Hz to 80 Hz, after 1 month and 12 months of chronic 80 Hz stimulation. RESULTS IM improved in most subjects after the switch of stimulation frequency: dyskinesias improved in 6/6 subjects and dystonic features in 3/4 subjects after one month of 80 Hz stimulation. However, the 130 Hz STN stimulation was restored in 4 subjects during the following months, because of a gradual worsening of parkinsonian symptoms. A sustained efficacy on motor features and IM was observed with 80 Hz stimulation frequency in the remaining patients. CONCLUSIONS In this limited cohort of STN-DBS patients, we observed an improvement of residual IM after the switch of stimulation frequency from 130 Hz to 80 Hz. However, a moderate worsening of parkinsonian symptoms was observed in a portion of patients, requiring to return at 130 Hz STN-DBS.

Subthalamic nucleus deep brain stimulation outcome in young onset Parkinson's disease: a role for age at disease onset?

Background Patients with young onset Parkinsons disease (YOPD) are often candidates for subthalamic nucleus–deep brain stimulation (STN–DBS). Nevertheless, few data have been reported on the long term STN–DBS clinical outcome of YOPD versus non-young onset Parkinsons disease (n-YOPD) patients. Aim In this study, the issue of whether YOPD might represent a long term positive predictive factor for STN–DBS was addressed, comparing follow-up data for 20 YOPD and 40 n-YOPD patients (20 treated after <15 years of disease duration and 20 treated after ≥15 years of disease duration). Materials and methods Mean scores for the Unified Parkinsons Disease Rating Scale (UPDRS) sections were compared 1 year, 5 years and, for 34 patients (12 YOPD and 22 n-YOPD), ≥7 years after surgery. Furthermore, a Cox proportional hazard regression model was used to determine the influence of age at PD onset, clinical phenotype, disease duration and duration of motor complications on the development of stimulation and medication resistant symptoms. Results YOPD patients showed a lower incidence of stimulation and medication resistant symptoms and a lower mortality rate; also, the tremor dominant clinical phenotype was associated with a lower risk of developing dementia, hallucinations and constipation. No significant differences in UPDRS scores were observed between n-YOPD patients treated after <15 years of PD and those treated after ≥15 years of PD. Conclusion In this series of STN–DBS treated patients, YOPD was associated with a medium to long term lower incidence of stimulation and medication resistant symptoms.

Probable REM sleep behaviour disorder and STN-DBS outcome in Parkinson's Disease

OBJECTIVE To assess whether the presence of probable REM sleep behaviour disorder (pRBD) influences the long-term outcome of Parkinsons Disease (PD) patients undergoing Subthalamic Nucleus Deep Brain Stimulation (STN-DBS). BACKGROUND RBD is a parasomnia characterized by loss of muscular atonia and complex motor behaviours during REM sleep, frequently reported in PD patients. Recent evidence suggests that RBD is associated with akinetic rigid disease type and increased frequency of falls. We wondered whether the presence of RBD would also influence the long-term outcome of STN-DBS. METHODS Forty-one consecutive PD patients treated with bilateral STN-DBS were assessed. The diagnosis of pRBD was based on a clinical interview investigating the occurrence of diagnostic criteria for RBD. The Unified Parkinsons Disease Rating Scale was used to compare the on- and off-medication conditions preoperatively and the on-stimulation/on- and off-medication conditions 1 and 3 years postoperatively. The general linear model for multivariate measures was used to analyse the interaction of pRBD with STN-DBS outcome measures. RESULTS pRBD was present in 12 out of 41 patients (29%) undergoing STN-DBS. Patients with pRBD had a significantly poorer outcome three years after STN-DBS compared to patients without pRBD, in particular for axial symptoms. CONCLUSIONS Our findings suggest that the presence of pRBD in PD patients undergoing STN-DBS may be associated with a less favourable outcome and a more prominent development of axial symptoms over time.