Effect of Intrathecal Baclofen on Pain and Quality of Life in Poststroke Spasticity.

Background and Purpose- Intrathecal baclofen (ITB) is an effective treatment for managing patients with severe poststroke spasticity, who can experience continued pain and decline in their quality of life (QoL). SISTERS (Spasticity In Stroke-Randomized Study) was a randomized, controlled, open-label, multicenter, phase 4 study to evaluate ITB therapy versus conventional medical management (CMM) with oral antispastic medications for treatment of poststroke spasticity. Methods- Poststroke patients with spasticity in ≥2 extremities and an Ashworth Scale score of ≥3 in ≥2 affected lower extremity muscle groups were randomized (1:1) to ITB (N=31) or CMM (N=29). Both treatment arms received physiotherapy throughout. The primary outcome was the change in average Ashworth Scale score in the lower extremities of the affected side from baseline to month 6. Here, we report results for secondary outcomes: pain via the Numeric Pain Rating Scale, health-related QoL by the EuroQol-5 dimensional 3 level utility score and health status visual analog scale score, stroke-specific QoL, and patient satisfaction. Analyses were performed on an intention-to-treat basis. Results- We observed significant treatment effects in favor of ITB over CMM for changes from baseline to month 6 in Numeric Pain Rating Scale scores for actual pain (ITB versus CMM: mean, -1.17 [SD, 3.17] versus 0.00 [3.29]; median, -1.00 versus 0.00; P=0.0380) and least pain (mean, -1.61 [2.29] versus 0.24 [3.07]; median, -1.00 versus 0.00; P=0.0136), and EuroQol-5 dimensional 3 level utility scores (mean, +0.09 [0.26] versus +0.01 [0.16]; median, +0.07 versus 0.00; P=0.0197). Between-group differences were not statistically significant for EuroQol-5 dimensional 3 level visual analog scale, stroke-specific QoL summary, or Numeric Pain Rating Scale worst pain scores, although ITB patients showed greater numeric improvements from baseline during follow-up. More ITB patients than CMM patients (73% versus 48%) were satisfied with the spasticity reduction at month 6. Conclusions- These data support that ITB therapy is associated with improvements in pain and QoL in poststroke patients. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT01032239.

Intrathecal baclofen therapy versus conventional medical management for severe poststroke spasticity: results from a multicentre, randomised, controlled, open-label trial (SISTERS).

BACKGROUND: Intrathecal baclofen (ITB) is a treatment option for patients with severe poststroke spasticity (PSS) who have not reached their therapy goal with other interventions. METHODS: 'Spasticity In Stroke-Randomised Study' (SISTERS) was a randomised, controlled, open-label, multicentre phase IV study to evaluate the efficacy and safety of ITB therapy versus conventional medical management (CMM) with oral antispastic medications for treatment of PSS. Patients with chronic stroke with spasticity in ≥2 extremities and an Ashworth Scale (AS) score ≥3 in at least two affected muscle groups in the lower extremities (LE) were randomised (1:1) to ITB or CMM. Both treatment arms received physiotherapy throughout. The primary outcome was the change in the average AS score in the LE of the affected body side from baseline to month 6. Analyses were performed for all patients as randomised (primary analysis) and all randomised patients as treated (safety analysis). RESULTS: Of 60 patients randomised to ITB (n=31) or CMM (n=29), 48 patients (24 per arm) completed the study. The primary analysis showed a significant effect of ITB therapy over CMM (mean AS score reduction, -0.99 (ITB) vs -0.43 (CMM); Hodges-Lehmann estimate, -0.667(95.1%CI -1.0000 to -0.1667); P=0.0140). More patients reported adverse events while receiving ITB (24/25 patients, 96%; 149 events) compared with CMM (22/35, 63%; 77 events), although events were generally consistent with the known safety profile of ITB therapy. CONCLUSIONS: These data support the use of ITB therapy as an alternative to CMM for treatment of generalised PSS in adults. TRIAL REGISTRATION NUMBER: NCT01032239; Results.

Sacral Neuromodulation with the InterStim System for Overactive Bladder: 3-Year Results from the French Prospective, Multicenter, Observational SOUNDS Study.

BACKGROUND: SOUNDS strengthens the evidence basis of sacral neuromodulation (SNM) for overactive bladder (OAB) through real-world data. OBJECTIVE: To analyze diary-based effectiveness, quality of life (QoL), disease severity, symptom bother, and safety data for SNM with the InterStim system up to 3 yr after implantation. DESIGN, SETTING, AND PARTICIPANTS: Twenty-five representative French sites enrolled 291 patients with OAB followed according to the local standard of care. Overall, 229 patients received a de novo or replacement InterStim implant and had four follow-up visits, two within the first yr and annually thereafter. A total of 190 patients completed the fourth follow-up visit after a mean of 33.7 ± 3.7 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The effectiveness outcomes measured were changes in daily voids and leaks and the therapy responder rates. Other outcomes included validated QoL data (Ditrovie and EuroQol 5-dimension 5-level questionnaires), disease severity (Urinary Symptom Profile [USP]), symptom bother rated using a numeric rating scale (NRS), and safety data. Follow-up data were compared to baseline results using the Wilcoxon signed-rank test. RESULTS AND LIMITATIONS: Average daily voids and leaks were significantly reduced at all time points up to 3 yr after implantation (p < 0.05) except for voids at 21 mo in the group receiving a replacement device. The therapeutic response for urinary urge incontinence at the fourth follow-up was 72% for the de novo group and 86% for the replacement group. Disease-specific QoL (Ditrovie), OAB-specific symptom severity (USP domain 2), and NRS-rated disease bother were significantly improved at all visits (p < 0.001). Device- or procedure-related adverse events occurred in 49% of patients, with 68% of the events classified as minor (Clavien-Dindo grade I or II). Surgical revisions were performed in 33% of patients, including permanent removal in 13%, over a mean exposure time of 44.4 ± 15.3 mo. CONCLUSIONS: This study confirms the safety and effectiveness of SNM for OAB and improvements in QoL and disease bother in real life. PATIENT SUMMARY: Our study in French patients with overactive bladder showed that disease symptoms and bother were significantly reduced and quality of life was significantly improved over a study duration of approximately 3 yr after implantation of a device to stimulate nerves that control the bladder. This trial is registered at ClinicalTrials.gov as NCT02186041.

Sacral Neuromodulation with the InterStim™ System for Intractable Lower Urinary Tract Dysfunctions (SOUNDS): Results of Clinical Effectiveness, Quality of Life, Patient-Reported Outcomes and Safety in a French Multicenter Observational Study.

BACKGROUND: Real-world data that support the use of sacral neuromodulation (SNM) for lower urinary tract dysfunctions are of continued interest. OBJECTIVE: To evaluate the effectiveness, quality of life (QoL), patient-reported outcomes (PROs), and safety of SNM with the InterStim™ system in real life during 1-yr postimplant. DESIGN, SETTING, AND PARTICIPANTS: This is a prospective, multicenter, observational study at 25 representative public and private French sites. Eligible patients received SNM therapy for overactive bladder (OAB) and non-obstructive urinary retention based on local standard of care. Overall, 320 patients were enrolled; 247 received permanent implant or replacement; 204 implanted patients completed second follow-up after mean of 10.0±3.8 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Effectiveness outcomes were change in voids, leaks, and catheterizations/day. Other outcomes included validated QoL and disease severity scores as well as PROs and adverse event data. Outcomes at follow-ups were compared with baseline using the Wilcoxon signed-rank test. RESULTS AND LIMITATIONS: Voids in urinary frequency (UF) and leaks/day in urinary urge incontinence (UI) patients were significantly reduced after 10 mo in both de novo (mean baseline voids/day UF de novo: 12.7 vs 8.6 after 10 mo; p<0.001; mean baseline leaks/day UI de novo: 4.3 vs 1.1 after 10 mo; p<0.001) and replacement patients (mean baseline voids/day UF replacement: 11.5 vs 7.9 after 10 mo; p<0.001; mean baseline leaks/day UI replacement: 5.4 vs 1.0 after 10 mo; p<0.001). Disease bother, Urinary Symptom Profile score, and Ditrovie questionnaire score were also significantly improved. Revisions postimplant occurred in 20% of patients including in 9% due to permanent explantation during a mean exposure time of 24.3 mo. CONCLUSIONS: Through a real-life study, SOUNDS (Sacral neuromOdUlation with InterStim™ therapy for intractable lower uriNary tract DySfunctions) confirms the clinical effectiveness, safety, and positive effect of SNM on QoL and PROs for the treatment of OAB patients. PATIENT SUMMARY: These analyses on French patients who received sacral neuromodulation (SNM) for retention or OAB during a 10-mo period showed that SNM improved OAB symptoms, quality of life, and reduced disease bother. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02186041.

The Surgical Approach to the Anterior Nucleus of Thalamus in Patients With Refractory Epilepsy: Experience from the International Multicenter Registry (MORE).

BACKGROUND: The Medtronic Registry for Epilepsy (MORE; Medtronic Inc, Dublin, Ireland) is an open label observational study evaluating the long-term effectiveness, safety, and performance of deep brain stimulation (DBS) of the anterior nucleus of thalamus (ANT) for the treatment of refractory epilepsy. OBJECTIVE: To compare the difference in success rate of placing contacts at ANT-target region (ANT-TR) between transventricular (TV) and extraventricular (EV) lead trajectories in 73 ANT-DBS implants in 17 European centers participating in the MORE registry. METHODS: The success rate of placing contacts at ANT-TR was evaluated using a screening method combining both individual patient imaging information and stereotactic atlas information to identify contacts at ANT-TR. RESULTS: EV lead trajectory was used in 53% of the trajectories. Approximately, 90% of the TV lead trajectories had at least 1 contact at ANT-TR, vs only 71% of the EV lead trajectories. The success rate for placing at least 1 contact at ANT-TR bilaterally was 84% for TV implants and 58% for EV implants (P < .05; Fisher's exact). No intracranial bleedings were observed, but 1 cortical infarct was reported following EV lead trajectory. CONCLUSION: The results of this registry support the use of TV lead trajectories for ANT-DBS as they have a higher probability in placing contacts at ANT-TR, without appearing to compromise procedural safety. Follow-up data collection is continuing in the MORE registry. These data will provide outcomes associated with TV and EV trajectories.

Prevalence of clinically significant functional fatigue or weakness in specialty outpatient clinics of Pune, India.

Disorders of fatigue are important in clinical practice but inadequately studied in developing countries. Questions about their consistency and variation across cultures also require attention. The standard professional diagnostic formulations of these disorders, namely, chronic fatigue syndrome and neurasthenia, are not used widely in India, perhaps due to lack of research and poor appreciation of their clinical significance. Recognising patients with clinically significant functional fatigue or weakness often seek help from various care-givers, prevalence of this condition was studied in four specialty clinics of Sassoon Hospital, Pune. An operationally defined set of criteria was used to create a screening instrument. Trained research assistants surveyed 1,874 consecutive patients from psychiatry, medicine, dermatology, and ayurved clinics. Data were entered and analysed to compute the rates of this condition, compare them across clinics and between sexes, and to compute rates adjusted for age, sex, and the clinic attended. Overall prevalence was 5.02% with higher rates in the dermatology and ayurved clinics than in psychiatry and medicine clinics. The female preponderance (63.83%) was notable (p < 0.001). Mean age of patients with this condition was similar across clinics. Logistic regression showed female sex (OR 2.19, 95% CI 1.41 to 3.40) and dermatology clinic (OR 1.70, 1.02 to 2.85) to be significant predictors of CS-FoW. Female preponderance indicates the need for studies with gender focus. Clinical and cultural epidemiological studies informing psychiatrists as well as other physicians are necessary. Need for counselling for majority of these patients calls for appropriate changes in healthcare delivery.