Long-term outcomes of CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) in a consecutive series of 12 patients.

BACKGROUND: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a central nervous system inflammatory disease. OBJECTIVE: To describe the disease course of CLIPPERS. DESIGN: A nationwide study was implemented to collect clinical, magnetic resonance imaging, cerebrospinal fluid, and brain biopsy specimen characteristics of patients with CLIPPERS. SETTING: Academic research. PATIENTS: Twelve patients with CLIPPERS. MAIN OUTCOME MEASURES: The therapeutic management of CLIPPERS was evaluated. RESULTS: Among 12 patients, 42 relapses were analyzed. Relapses lasted a mean duration of 2.5 months, manifested frequent cerebellar ataxia and diplopia, and were associated with a mean Expanded Disability Status Scale (EDSS) score of 4. Besides typical findings of CLIPPERS, magnetic resonance imaging showed brainstem mass effect in 5 patients, extensive myelitis in 3 patients, and closed ring enhancement in 1 patient. Inconstant oligoclonal bands were found on cerebrospinal fluid investigation in 4 patients, with an increased T-cell ratio of CD4 to CD8. Among 7 available brain biopsy specimens, staining was positive for perivascular CD4 T lymphocytes in 5 samples. Thirty-eight of 42 relapses were treated with pulse corticosteroid therapy, which led to improvement, with a mean residual EDSS score of 1.9 (range, 0-7). In 1 patient with untreated relapses, scores on the EDSS progressively increased to a score of 10 at death. Among 5 patients without long-term corticosteroid therapy, the mean annualized relapse rate was 0.5 (range, 0.25-2.8). Among 7 patients taking oral corticosteroids, no relapses occurred in those whose daily dose was 20 mg or higher. No progressive course of CLIPPERS was observed. Four patients with a final EDSS score of 4 or higher had experienced previous severe relapses (EDSS score, ≥5) and brainstem and spinal cord atrophy. CONCLUSIONS: CLIPPERS is a relapsing-remitting disorder without progressive forms. Long-term disability is correlated with the severity of previous relapses. Further studies are needed to confirm that prolonged corticosteroid therapy prevents further relapses.journal article2012 Julimporte

Programming parameters of subthalamic deep brain stimulators in Parkinson's disease from a controlled trial.

BACKGROUND Programming algorithms have never been tested for outcome. The EARLYSTIM study showed superior outcomes of deep brain stimulation of the subthalamic nucleus (STN-DBS) over best medical treatment in early Parkinson's disease (PD). Patients were programmed according to common guidelines but customized for each patient. METHODS Stimulation parameters were systematically documented at 1, 5, 12, and 24 month in the cohort of 114 patients who had bilateral STN-DBS at 24 month. We investigated the influence of atypical programming, changes of stimulated electrode contacts and stimulation energy delivered. Outcomes were the Unified Parkinson's Disease Rating Scale (UPDRS) motor and ADL-subscores, health-related quality of life (PDQ-39) summary index and mobility- and ADL-subscores. RESULTS At 1/5/12/24 months follow up, mean amplitude (1.8/2.5/2.6/2.8 V), impedance (1107/1286/1229/1189 Ω) and TEED (33.7/69.0/84.4/93.0 V2*μs*Hz/Ω) mainly increased in the first 5 months, while mean pulse width (60.0/62.5/65.1/65.8 μs), frequency (130/137.7/139.1/142.7 Hz) remained relatively stable. Typical programming (single monopolar electrode contact) was used in 80.7% of electrodes. Double monopolar (11/114) and bipolar (2/114) stimulation was only rarely required. There was no significant difference in clinical outcomes between the patient groups requiring contact changes (n = 32/28.1%) nor between typical (n = 83/72.8%) versus non-typical programming. Energy used for STN-DBS was higher for the dominant side of PD. CONCLUSION In the first 5 months an increase in amplitude is required to compensate for various factors. Monopolar stimulation is sufficient in 80% of patients at 24 months. Homogeneous stimulation strategies can account for the favorable outcomes reported in the Earlystim study

Behavioural outcomes of subthalamic stimulation and medical therapy versus medical therapy alone for Parkinson's disease with early motor complications (EARLYSTIM trial): secondary analysis of an open-label randomised trial

Background Although subthalamic stimulation is a recognised treatment for motor complications in Parkinson's disease, reports on behavioural outcomes are controversial, which represents a major challenge when counselling candidates for subthalamic stimulation. We aimed to assess changes in behaviour in patients with Parkinson's disease receiving combined treatment with subthalamic stimulation and medical therapy over a 2-year follow-up period as compared with the behavioural evolution under medical therapy alone. Methods We did a parallel, open-label study (EARLYSTIM) at 17 surgical centres in France (n=8) and Germany (n=9). We recruited patients with Parkinson's disease who were disabled by early motor complications. Participants were randomly allocated (1: 1) to either medical therapy alone or bilateral subthalamic stimulation plus medical therapy. The primary outcome was mean change in quality of life from baseline to 2 years. A secondary analysis was also done to assess behavioural outcomes. We used the Ardouin Scale of Behavior in Parkinson's Disease to assess changes in behaviour between baseline and 2-year follow-up. Apathy was also measured using the Starkstein Apathy Scale, and depression was assessed with the Beck Depression Inventory. The secondary analysis was done in all patients recruited. We used a generalised estimating equations (GEE) regression model for individual items and mixed model regression for subscores of the Ardouin scale and the apathy and depression scales. This trial is registered with ClinicalTrials.gov, number NCT00354133. The primary analysis has been reported elsewhere; this report presents the secondary analysis only. Findings Between July, 2006, and November, 2009, 251 participants were recruited, of whom 127 were allocated medical therapy alone and 124 were assigned bilateral subthalamic stimulation plus medical therapy. At 2-year follow-up, the levodopa-equivalent dose was reduced by 39% (-363.3 mg/day [SE 41.8]) in individuals allocated bilateral subthalamic stimulation plus medical therapy and was increased by 21% (245.8 mg/day [40.4]) in those assigned medical therapy alone (p<0.0001). Neuropsychiatric fluctuations decreased with bilateral subthalamic stimulation plus medical therapy during 2-year follow-up (mean change -0.65 points [SE 0.15]) and did not change with medical therapy alone (-0.02 points [0.15]); the between-group difference in change from baseline was significant (p=0.0028). At 2 years, the Ardouin scale subscore for hyperdopaminergic behavioural disorders had decreased with bilateral subthalamic stimulation plus medical therapy (mean change -1.26 points [SE 0.35]) and had increased with medical therapy alone (1.12 points [0.35]); the between-group difference was significant (p<0.0001). Mean change from baseline at 2 years in the Ardouin scale subscore for hypodopaminergic behavioural disorders, the Starkstein Apathy Scale score, and the Beck Depression Inventory score did not differ between treatment groups. Antidepressants were stopped in 12 patients assigned bilateral subthalamic stimulation plus medical therapy versus four patients allocated medical therapy alone. Neuroleptics were started in nine patients assigned medical therapy alone versus one patient allocated bilateral subthalamic stimulation plus medical therapy. During the 2-year follow-up, two individuals assigned bilateral subthalamic stimulation plus medical therapy and one patient allocated medical therapy alone died by suicide. Interpretation In a large cohort with Parkinson's disease and early motor complications, better overall behavioural outcomes were noted with bilateral subthalamic stimulation plus medical therapy compared with medical therapy alone. The presence of hyperdopaminergic behaviours and neuropsychiatric fluctuations can be judged additional arguments in favour of subthalamic stimulation if surgery is considered for disabling motor complications