Beta-triggered adaptive deep brain stimulation during reaching movement in Parkinson's disease.

Subthalamic nucleus (STN) beta-triggered adaptive deep brain stimulation (ADBS) has been shown to provide clinical improvement comparable to conventional continuous DBS (CDBS) with less energy delivered to the brain and less stimulation induced side effects. However, several questions remain unanswered. First, there is a normal physiological reduction of STN beta band power just prior to and during voluntary movement. ADBS systems will therefore reduce or cease stimulation during movement in people with Parkinson's disease and could therefore compromise motor performance compared to CDBS. Second, beta power was smoothed and estimated over a time period of 400 ms in most previous ADBS studies, but a shorter smoothing period could have the advantage of being more sensitive to changes in beta power, which could enhance motor performance. In this study, we addressed these two questions by evaluating the effectiveness of STN beta-triggered ADBS using a standard 400 ms and a shorter 200 ms smoothing window during reaching movements. Results from 13 people with Parkinson's disease showed that reducing the smoothing window for quantifying beta did lead to shortened beta burst durations by increasing the number of beta bursts shorter than 200 ms and more frequent switching on/off of the stimulator but had no behavioural effects. Both ADBS and CDBS improved motor performance to an equivalent extent compared to no DBS. Secondary analysis revealed that there were independent effects of a decrease in beta power and an increase in gamma power in predicting faster movement speed, while a decrease in beta event related desynchronization (ERD) predicted quicker movement initiation. CDBS suppressed both beta and gamma more than ADBS, whereas beta ERD was reduced to a similar level during CDBS and ADBS compared with no DBS, which together explained the achieved similar performance improvement in reaching movements during CDBS and ADBS. In addition, ADBS significantly improved tremor compared with no DBS but was not as effective as CDBS. These results suggest that STN beta-triggered ADBS is effective in improving motor performance during reaching movements in people with Parkinson's disease, and that shortening of the smoothing window does not result in any additional behavioural benefit. When developing ADBS systems for Parkinson's disease, it might not be necessary to track very fast beta dynamics; combining beta, gamma, and information from motor decoding might be more beneficial with additional biomarkers needed for optimal treatment of tremor.

Taking the knife to neurodegeneration: a review of surgical gene therapy delivery to the CNS.

Gene supplementation and editing for neurodegenerative disorders has emerged in recent years as the understanding of the genetic mechanisms underlying several neurodegenerative disorders increases. The most common medium to deliver genetic material to cells is via viral vectors; and with respect to the central nervous system, adeno-associated viral (AAV) vectors are a popular choice. The most successful example of AAV-based gene therapy for neurodegenerative disorders is Zolgensma© which is a transformative intravenous therapy given to babies with spinal muscular atrophy. However, the field has stalled in achieving safe drug delivery to the central nervous system in adults for which treatments for disorders such as amyotrophic lateral sclerosis are desperately needed. Surgical gene therapy delivery has been proposed as a potential solution to this problem. While the field of the so-called regenerative neurosurgery has yielded pre-clinical optimism, several challenges have emerged. This review seeks to explore the field of regenerative neurosurgery with respect to AAV-based gene therapy for neurodegenerative diseases, its progress so far and the challenges that need to be overcome.

Butterfly gliomas: a time for stratified management?

Butterfly glioblastomas (bGBM) are a rare subset of WHO grade IV tumours that carry a poor prognosis with a median survival ranging between 3.3 to 6 months. Given their poor prognosis, there is debate over whether histological diagnosis with a biopsy or any surgical or oncological intervention alters disease progression. With this in mind, we reviewed our experience as a high-volume unit to evaluate management decisions and outcomes. A retrospective analysis was undertaken (January 2009 to June 2021) of the electronic patient records of a large neurosurgical centre. We assessed patient demographics, initial clinical presentation, tumour characteristics, clinical management and overall survival (Kaplan-Meier estimator, log-rank analysis and cox proportional hazard analysis). Eighty cases of bGBM were identified. These patients were managed with biopsy ± adjuvant therapy (36), with radiotherapy alone without biopsy (3), or through surgical resection (3). Thirty-eight cases of suspected bGBM were managed conservatively, receiving no oncological treatment or surgical resection/biopsy for histological diagnosis. Those managed conservatively and with radiotherapy without biopsy were diagnosed at neuro-oncology multidisciplinary meeting (MDT) based on clinical presentation and radiological imaging. No significant difference in survival was seen between conservative management compared with single adjuvant treatment (p = 0.69). However, survival was significantly increased when patients received dual adjuvant chemoradiotherapy following biopsy or resection (p = 0.002). A Cox Proportional Hazards model found that survival was significantly impacted by the oncology treatment (p < 0.001), but was not significantly related to potential confounding variables such as the patient's age (p = 0.887) or KPS (p = 0.057). Butterfly glioblastoma have a poor prognosis. Our study would suggest that unless a patient is planned for adjuvant chemoradiotherapy following biopsy, they should be managed conservatively. This avoids unnecessary procedural interventions with the associated morbidities and costs.

The ASPECT Hydrocephalus System: a non-hierarchical descriptive system for clinical use.

In patients with hydrocephalus, prognosis and intervention are based on multiple factors. This includes, but is not limited to, time of onset, patient age, treatment history, and obstruction of cerebrospinal fluid flow. Consequently, several distinct hydrocephalus classification systems exist. The International Classification of Diseases (ICD) is universally applied, but in ICD-10 and the upcoming ICD-11, hydrocephalus diagnoses incorporate only a few factors, and the hydrocephalus diagnoses of the ICD systems are based on different clinical measures. As a consequence, multiple diagnoses can be applied to individual cases. Therefore, similar patients may be described with different diagnoses, while clinically different patients may be diagnosed identically. This causes unnecessary dispersion in hydrocephalus diagnostics, rendering the ICD classification of little use for research and clinical decision-making. This paper critically reviews the ICD systems for scientific and functional limitations in the classification of hydrocephalus and presents a new descriptive system. We propose describing hydrocephalus by a system consisting of six clinical key factors of hydrocephalus: A (anatomy); S (symptomatology); P (previous interventions); E (etiology); C (complications); T (time-onset and current age). The "ASPECT Hydrocephalus System" is a systematic, nuanced, and applicable description of patients with hydrocephalus, with a potential to resolve the major issues of previous classifications, thus providing new opportunities for standardized treatment and research.

Inter-dural spinal cyst with acute thoracic compressive myelopathy: anatomical aspects of spinal dura, case report and literature review.

INTRODUCTION: Inter-dural juxta-facet spinal cysts occur rarely. They form as part of the degenerative spinal disease process and can be misdiagnosed as synovial cysts or ganglion cysts. We report the case of a thoracic inter-dural juxta-facet spinal cyst causing acute compressive thoracic myelopathy. METHODS: The data was collected retrospectively from patient records. The literature review was performed in PubMed. RESULTS: We report a case of symptomatic inter-dural juxta-facet thoracic spinal cyst. The literature review showed a variety of different spinal cysts including arachnoid cyst, discal cyst, ganglion cyst, epidermoid cyst and synovial cysts. Micro-instability and repeated microtrauma associated with degenerative changes are most likely contributors to its formation. Asymptomatic cysts can show spontaneous resolution. When symptomatic, they can be managed with surgical excision with good patient outcome. CONCLUSION: Inter-dural spinal cysts can be diagnosed and surgically excised to produce excellent post-operative outcome. High pre-operative index of suspicion of this diagnosis together with good understanding of the intraoperative anatomy are essential to avoid inadvertent dural breach.

Xanthogranulomatous osteomyelitis of the cervical spine.

BACKGROUND: Xanthogranulomatous Osteomyelitis is a rare form of chronic inflammation described in a handful of cases in the reported literature involving the long bones of the axial skeleton. To the authors knowledge it has not been reported in the spinal column. CASE: We report a case of a 65 year old female presenting with features of metastatic cord compression and an expansile lesion affecting the 5th -7th cervical vertebrae. She underwent vertebrectomy, insertion of an expandable cage and plating to good effect. A histological diagnosis of Xanthogranulomatous Osteomyelitis was made. CONCLUSIONS: We report what the authors believe to be the first case in the literature of xanthogranulomatous osteomyelitis affecting the spine. In this case the patient was managed with a vertebrectomy without the need for antibiotics.

Mono-segment fixation of thoracolumbar burst fractures.

OBJECT: To investigate what benefits can be derived from a shorter construct length in the pedicle screw based surgical treatment of thoracolumbar burst fracture (TLBF). METHODS: A retrospective analysis was performed of clinical notes and radiology for patients who underwent surgical fixation of TLBFs between 2007 and 2012 in a single UK institution. Constructs either fixed the vertebra above the fracture to the vertebra below (short segment fixation - SSF) or fixed the vertebra above to the relatively well-preserved pedicles and inferolateral portions of the bodies of the fractured vertebra (mono-segment fixation - MSF). 11 patients in each group were included and length of operation, postoperative opiate use, time to mobilisation and length of hospital stay were recorded. Anterior vertebral height loss (AVHL) was measured from sagittal reconstructions of CT imaging and lateral radiographs. RESULTS: The mean operation time was 169 ± 10.4 min in the MSF group compared to 227 ± 13.3 minin the SSF group (p = 0.0028). Mean postoperative opiate use was 50.4 ± 17.9 mg in the MSF group compared to 126.6 ± 64.6 mgs in the SSF group (p = 0.3088, ns). Mean time to mobilisation was 1.3 ± 0.2 in the MSF group and 3.4 ± 1.3 in the SSF group (p = 0.1031, ns). There were no significant differences in progression of anterior vertebral height loss or hospital stay between the two groups. CONCLUSIONS: MSF for TLBFs is associated with shorter operative times than SSF. Strong trends are also demonstrated to quicker mobilisation, and lower opiate use. These advantages of a shorter construct length may result in cost saving and echo the advantages claimed by others for reducing spinal exposure in minimally invasive spinal surgery.

Low molecular weight heparin versus unfractionated heparin in the management of cerebral venous thrombosis: A systematic review and meta-analysis.

INTRODUCTION: There are two main choices of anti-coagulation in cerebral venous thrombosis: Unfractionated heparin versus low molecular weight heparin. A consensus is yet to be reached regarding which agent is optimal. Therefore the aim of this systematic review and meta-analysis was to identify which agent is most effective in treating CVT. METHODS: Databases Pubmed (MEDLINE), Google Scholar and hand-picked references from papers of interest were reviewed. Studies comparing the use of low molecular weight heparin and unfractionated heparin in adult patients with a confirmed diagnosis of cerebral vein thrombosis were selected. Data was recorded for patient mortality, functional outcome and haemorrhagic complications of therapy. RESULTS: A total of 2761 papers were identified, 74 abstracts were screened, with 5 papers being read in full text and three studies suitable for final inclusion. A total of 179 patients were in the LMWH group and 352 patients were in the UH group. Mortality and functional outcome trended towards favouring LMWH with OR [95% CI] of 0.51 [0.23, 1.10], p = 0.09 and 0.79 [0.49, 1.26] p = 0.32 respectively. There was no difference in extra-cranial haemorrhage rates between either agent with a OR [95% CI] of 1.00 [0.29, 3.52] p = 0.99. CONCLUSION: Trends towards improved mortality and improved functional outcomes were seen in patients treated with LMWH. No result reached statistical significance due to low numbers of studies available for inclusion. There is a need for further large scale randomized trials to definitively investigate the potential benefits of LMWH in the treatment of CVT.

Intramuscular Local Anesthetic Infiltration at Closure for Postoperative Analgesia in Lumbar Spine Surgery: A Systematic Review and Meta-Analysis.

STUDY DESIGN: Systematic Review and Meta-Analysis OBJECTIVE.: To identify whether intramuscular local anesthetic infiltration prior to wound closure was effective in reducing postoperative pain and facilitating early discharge following lumbar spine surgery. SUMMARY OF BACKGROUND DATA: Local anesthetic infiltration prior to wound closure may form part of the multimodal strategy for postoperative analgesia, facilitating early mobilization and discharge. Although there are a number of small studies investigating its utility, a quantitative meta-analysis of the data has never been performed. METHODS: This review was conducted according the PRISMA statement and was registered with the PROSPERO database. Only randomized controlled trials were eligible for inclusion. Key outcomes of interest included time to first analgesic demand, total postoperative opiate usage in the first 24 hours, visual analogue score (VAS) at 1, 12 and 24 hours and postoperative length of stay. RESULTS: Eleven publications fulfilled the inclusion criteria. A total of 438 patients were include; 212 in the control group and 226 in the intervention group. Local anesthetic infiltration resulted in a prolonged time to first analgesic demand (mean difference (MD) 65.88 minutes, 95% confidence interval (95% CI) 23.70 to 108.06, P.0.002) as well as a significantly reduced postoperative opiate demand (M.D. -9.71 mg, 95% CI -15.07, -4.34, p = 0.0004). There was a small but statistically significant reduction in postoperative visual analogue score (VAS) at 1 hour (M.D. -0.87 95%CI -1.55, -0.20, p = 0.01), but no significant reduction at 12 or 24 hours (p = 0.93 and 0.85 respectively). CONCLUSION: This systematic review and meta-analysis provides evidence that postoperative intramuscular local anaesthetic infiltration reduces postoperative analgesic requirements and the time to first analgesic demands for patients undergoing lumbar spine surgery. Key research priorities include optimization of the choice and strength of local anaesthetic agent and health-economic analyses to strengthen the case for routine use of postoperative local anesthetics in lumbar spine surgery. LEVEL OF EVIDENCE: 1.

Diagnosis of a growing radiation-induced skull lesion in a patient: an unusual scar.

New lesions arising from within an area of previous irradiation often present a diagnostic dilemma, with new malignancy or metastasis of particular concern. The authors report a case of reactive fibroblast proliferation emerging from a previous radiation field and presenting as a growing lesion of the frontal and parietal skull. Following complete gross resection of the skull lesion and histopathological analysis, it was discovered that this lesion consisted of dense fibroblast proliferation with areas of osteonecrosis. This unusual reactive phenomenon offers a novel differential diagnosis for a new contrast-enhancing lesion in a region of previous radiation.