Characterization of anti-seizure medication reduction and discontinuation rates following epilepsy surgery.

OBJECTIVE: Many patients pursue epilepsy surgery with the hope of reducing or stopping anti-seizure medications (ASMs), in addition to reducing their seizure frequency and severity. While ASM decrease is primarily driven by surgical outcomes and patient preferences, preoperative estimates of meaningful ASM reduction or discontinuation are uncertain, especially when accounting for the various forking paths possible following intracranial EEG (iEEG), including resection, neuromodulation, or even the absence of further surgery. Here, we characterize in detail the ASM reduction in a large cohort of patients who underwent iEEG, facilitating proactive, early counseling for a complicated cohort considering surgical treatment. METHODS: We identified a multi-institutional cohort of patients who underwent iEEG between 2001 and 2022, with a minimum of two years follow-up. The total number of ASMs prescribed immediately prior to surgery, choice of investigation modality, and subsequent surgical treatment were extracted for each patient. Primary endpoints included decreases in ASM counts from preoperative baseline to various follow-up intervals. RESULTS: A total of 284 patients were followed for a median of 6.0 (range 2,22) years after iEEG surgery. Patients undergoing resection saw an average reduction of âˆ¼ 0.5 ASMs. Patients undergoing neuromodulation saw no decrease and trended towards requiring increased ASM usage during long-term follow-up. Only patients undergoing resection were likely to completely discontinue all ASMs, with an increasing probability over time approaching âˆ¼ 10 %. Up to half of resection patients saw ASM decreases, which was largely stable during long-term follow-up, whereas only a quarter of neuromodulation patients saw a reduction, though their ASM reduction decreased over time. CONCLUSIONS: With the increasing use of stereotactic EEG and non-curative neuromodulation procedures, realistic estimates of ASM reduction and discontinuation should be considered preoperatively. Almost half of patients undergoing resective surgery can expect to reduce their ASMs, though only a tenth can expect to discontinue ASMs completely. If reduction is not seen early, it likely does not occur later during long-term follow-up. Less than a third of patients undergoing neuromodulation can expect ASM reduction, and instead most may require increased usage during long-term follow-up.

Seizure onset patterns predict outcome after stereo-electroencephalography-guided laser amygdalohippocampotomy.

OBJECTIVE: Stereotactic laser amygdalohippocampotomy (SLAH) is an appealing option for patients with temporal lobe epilepsy, who often require intracranial monitoring to confirm mesial temporal seizure onset. However, given limited spatial sampling, it is possible that stereotactic electroencephalography (stereo-EEG) may miss seizure onset elsewhere. We hypothesized that stereo-EEG seizure onset patterns (SOPs) may differentiate between primary onset and secondary spread and predict postoperative seizure control. In this study, we characterized the 2-year outcomes of patients who underwent single-fiber SLAH after stereo-EEG and evaluated whether stereo-EEG SOPs predict postoperative seizure freedom. METHODS: This retrospective five-center study included patients with or without mesial temporal sclerosis (MTS) who underwent stereo-EEG followed by single-fiber SLAH between August 2014 and January 2022. Patients with causative hippocampal lesions apart from MTS or for whom the SLAH was considered palliative were excluded. An SOP catalogue was developed based on literature review. The dominant pattern for each patient was used for survival analysis. The primary outcome was 2-year Engel I classification or recurrent seizures before then, stratified by SOP category. RESULTS: Fifty-eight patients were included, with a mean follow-up duration of 39 ± 12 months after SLAH. Overall 1-, 2-, and 3-year Engel I seizure freedom probability was 54%, 36%, and 33%, respectively. Patients with SOPs, including low-voltage fast activity or low-frequency repetitive spiking, had a 46% 2-year seizure freedom probability, compared to 0% for patients with alpha or theta frequency repetitive spiking or theta or delta frequency rhythmic slowing (log-rank test, p = .00015). SIGNIFICANCE: Patients who underwent SLAH after stereo-EEG had a low probability of seizure freedom at 2 years, but SOPs successfully predicted seizure recurrence in a subset of patients. This study provides proof of concept that SOPs distinguish between hippocampal seizure onset and spread and supports using SOPs to improve selection of SLAH candidates.

Single cell RNA sequencing of human microglia uncovers a subset associated with Alzheimer's disease.

The extent of microglial heterogeneity in humans remains a central yet poorly explored question in light of the development of therapies targeting this cell type. Here, we investigate the population structure of live microglia purified from human cerebral cortex samples obtained at autopsy and during neurosurgical procedures. Using single cell RNA sequencing, we find that some subsets are enriched for disease-related genes and RNA signatures. We confirm the presence of four of these microglial subpopulations histologically and illustrate the utility of our data by characterizing further microglial cluster 7, enriched for genes depleted in the cortex of individuals with Alzheimer's disease (AD). Histologically, these cluster 7 microglia are reduced in frequency in AD tissue, and we validate this observation in an independent set of single nucleus data. Thus, our live human microglia identify a range of subtypes, and we prioritize one of these as being altered in AD.

Three-year follow-up of prospective trial of focused ultrasound thalamotomy for essential tremor.

OBJECTIVE: To test the hypothesis that transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) thalamotomy is effective, durable, and safe for patients with medication-refractory essential tremor (ET), we assessed clinical outcomes at 3-year follow-up of a controlled multicenter prospective trial. METHODS: Outcomes were based on the Clinical Rating Scale for Tremor, including hand combined tremor-motor (scale of 0-32), functional disability (scale of 0-32), and postural tremor (scale of 0-4) scores, and total scores from the Quality of Life in Essential Tremor Questionnaire (scale of 0-100). Scores at 36 months were compared with baseline and at 6 months after treatment to assess for efficacy and durability. Adverse events were also reported. RESULTS: Measured scores remained improved from baseline to 36 months (all p < 0.0001). Range of improvement from baseline was 38%-50% in hand tremor, 43%-56% in disability, 50%-75% in postural tremor, and 27%-42% in quality of life. When compared to scores at 6 months, median scores increased for hand tremor (95% confidence interval [CI] 0-2, p = 0.0098) and disability (95% CI 1-4, p = 0.0001). During the third follow-up year, all previously noted adverse events remained mild or moderate, none worsened, 2 resolved, and no new adverse events occurred. CONCLUSIONS: Results at 3 years after unilateral tcMRgFUS thalamotomy for ET show continued benefit, and no progressive or delayed complications. Patients may experience mild degradation in some treatment metrics by 3 years, though improvement from baseline remains significant. CLINICALTRIALSGOV IDENTIFIER: NCT01827904. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with severe ET, unilateral tcMRgFUS thalamotomy provides durable benefit after 3 years.

Neoadjuvant temozolomide followed by complete resection of a 1p- and 19q-deleted anaplastic oligoastrocytoma: case study.

A 38-year-old woman presented with an infiltrative tumor of the right frontal lobe and genu of the corpus callosum that was deemed only partially resectable. A stereotactic biopsy was performed, which revealed a right frontal oligoastrocytoma that had some anaplastic features as well as allelic loss of chromosome arms 1p and 19q. The patient was treated with temozolomide for 24 months. The partial response of the tumor to chemotherapy rendered the lesion amenable to gross total resection, which was performed subsequently. The patient remains alive and well without evidence of recurrence 7 months after resection and 48 months after initial diagnosis. Thus, preoperative chemotherapy decreased tumor mass to a degree that subsequently enabled a gross total resection. This treatment strategy, although common in the treatment of other solid tumors, is rarely utilized in adult neuro-oncology and raises another potential role for chromosome testing in oligodendroglial tumor management.

Long-term recurrence rates of atypical meningiomas after gross total resection with or without postoperative adjuvant radiation.

OBJECTIVE: Atypical meningioma (AM) patients often undergo gross total resection (GTR) at the time of presentation, but subsequent prognosis and optimal management remain unclear. We sought to define the long-term recurrence rate of AMs after GTR, along with factors predicting recurrence, including postoperative radiation. METHODS: We performed a retrospective review of 108 AMs after GTR at our institution from 1993 to 2004. Recurrence risk factors were analyzed using multivariate Cox regression. RESULTS: There were 600 patient-years of imaging follow-up on 48 men and 60 women. Of 108 tumors, 30 (28%) recurred 3 to 144 months after GTR (mean, 36 months). Actuarial tumor recurrence rates were 7% (1 year), 41% (5 years), and 48% (10 years). Of 108 patients, 8 received postoperative radiation without recurrence (P = 0.1). Multivariate analysis including age, sex, postoperative radiation, tumor location, MIB-1 labeling index, and 6 atypical-defining histological features identified recurrence-predicting factors: older age (hazard ratio, 1.6/decade; P = 0.01), sheeting (hazard ratio, 2.2; P = 0.025), and prominent nucleoli (hazard ratio, 2.1; P = 0.034). Recursive partitioning identified a subset, men with mitoses and prominent nucleoli, with 70% recurrence (n = 14). All patients with recurrences received radiation, and 22 of 30 patients underwent craniotomies (average, 2.7 craniotomies per patient with recurrence; range, 1-7 craniotomies). Only 1 of 22 re-resected meningiomas underwent malignant transformation. Of 30 patients with recurrence, 10 experienced tumor-induced mortality an average of 7 years after recurrence (range, 1-14 years). CONCLUSION: After GTR without postoperative radiation, AMs have a high recurrence rate. Most recurrences occurred within 5 years after resection. Recurrences caused numerous reoperations per patient and shortened survival. Our finding suggesting lower recurrence rates in patients undergoing immediate postoperative radiation should be investigated in larger, prospective series.