Rehabilitation versus surgical reconstruction for non-acute anterior cruciate ligament injury (ACL SNNAP): a pragmatic randomised controlled trial.

BACKGROUND: Anterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability. METHODS: We did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score-4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367. FINDINGS: Between Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5-13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications. INTERPRETATION: Surgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management. FUNDING: The UK National Institute for Health Research Health Technology Assessment Programme.

Parkinson Disease and Subthalamic Nucleus Deep Brain Stimulation: Cognitive Effects in GBA Mutation Carriers.

OBJECTIVE: This study was undertaken to compare the rate of change in cognition between glucocerebrosidase (GBA) mutation carriers and noncarriers with and without subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson disease. METHODS: Clinical and genetic data from 12 datasets were examined. Global cognition was assessed using the Mattis Dementia Rating Scale (MDRS). Subjects were examined for mutations in GBA and categorized as GBA carriers with or without DBS (GBA+DBS+, GBA+DBS-), and noncarriers with or without DBS (GBA-DBS+, GBA-DBS-). GBA mutation carriers were subcategorized according to mutation severity (risk variant, mild, severe). Linear mixed modeling was used to compare rate of change in MDRS scores over time among the groups according to GBA and DBS status and then according to GBA severity and DBS status. RESULTS: Data were available for 366 subjects (58 GBA+DBS+, 82 GBA+DBS-, 98 GBA-DBS+, and 128 GBA-DBS- subjects), who were longitudinally followed (range = 36-60 months after surgery). Using the MDRS, GBA+DBS+ subjects declined on average 2.02 points/yr more than GBA-DBS- subjects (95% confidence interval [CI] = -2.35 to -1.69), 1.71 points/yr more than GBA+DBS- subjects (95% CI = -2.14 to -1.28), and 1.49 points/yr more than GBA-DBS+ subjects (95% CI = -1.80 to -1.18). INTERPRETATION: Although not randomized, this composite analysis suggests that the combined effects of GBA mutations and STN-DBS negatively impact cognition. We advise that DBS candidates be screened for GBA mutations as part of the presurgical decision-making process. We advise that GBA mutation carriers be counseled regarding potential risks associated with STN-DBS so that alternative options may be considered. ANN NEUROL 2022;91:424-435.

Deep Brain Stimulation for Recovery of Consciousness in Minimally Conscious Patients After Traumatic Brain Injury: A Systematic Review.

OBJECTIVES: Minimally conscious state (MCS) is a disorder of consciousness in which minimal but definite behavioral evidence of self-awareness or environmental awareness is demonstrated. Deep brain stimulation (DBS) of various targets has been used to promote recovery in patients with disorders of consciousness with varying results. The aim of this systematic review was to assess the effects of DBS in MCS following traumatic brain injury (TBI). MATERIALS AND METHODS: A systematic literature review was carried out using a number of electronic bibliographic data bases to identify relevant studies. We included all studies describing applications of DBS on patients in MCS following TBI. RESULTS: Eight studies were identified, including a total of ten patients, aged 15-58 years. The time from injury to stimulation ranged from 3 to 252 months, with the duration of follow-up post-DBS ranging from 10 to 120 months. Seven patients improved their postsurgical outcome score measures (three patients with the coma recovery scale, one with the near coma scale, and three with the Glasgow outcome score). A descriptive favorable outcome was reported in one patient. Two patients were reported not to have shown any improvements following the intervention. CONCLUSIONS: Current evidence is based on a small population of heterogeneous patients. The time from injury to stimulation was significantly variable and problematic, as spontaneous recovery can occur within the first year of injury. Although seven patients showed promising results in validated outcome measures, evidence supporting the use of DBS in MCS patients following TBI is lacking. There is need for controlled and randomized studies.

GBA-Associated Parkinson's Disease: Progression in a Deep Brain Stimulation Cohort.

BACKGROUND: Recent evidence suggests that glucosidase beta acid (GBA) mutations predispose Parkinson's disease (PD) patients to a greater burden of cognitive impairment and non-motor symptoms. This emerging knowledge has not yet been considered in patients who have undergone deep brain stimulation (DBS); a surgery that is generally contraindicated in those with cognitive deficits. OBJECTIVE: To explore the long-term phenotypic progression of GBA-associated PD, in a DBS cohort. METHODS: Thirty-four PD patients who had undergone DBS surgery between 2002 and 2011 were included in this study; 17 patients with GBA mutations were matched to 17 non-carriers. Clinical evaluation involved the administration of four assessments: The Mattis Dementia Rating Scale was used to assess cognitive function; non-motor symptoms were assessed using the Non-Motor Symptom Assessment Scale for PD; quality of life was measured using the Parkinson's Disease Questionnaire; and motor symptoms were evaluated using part III of the Movement Disorders Society Unified Parkinson's Disease Rating Scale, in on-medication/on-stimulation conditions. Levodopa equivalent doses (LED) and DBS settings were compared with clinical outcomes. RESULTS: At a mean follow-up of 7.5 years after DBS, cognitive impairment was more prevalent (70% vs 19%) and more severe in GBA mutation carriers compared to non-carriers (60% vs 6% were severely impaired). Non-motor symptoms were also more severe and quality of life more impaired in GBA-associated PD. Motor symptoms, LED, and stimulation settings were not significantly different between groups at follow-up. CONCLUSIONS: GBA status appears to be an important predictor for non-motor symptom disease progression, after deep brain stimulation surgery.