Citations

Abstract Temporal lobe epilepsy is a common neurological disease characterized by recurrent seizures that often originate within limbic networks involving amygdala and hippocampus. The limbic network is involved in crucial physiologic functions involving memory, emotion and sleep. Temporal lobe epilepsy is frequently drug-resistant, and people often experience comorbidities related to memory, mood and sleep. Deep brain stimulation targeting the anterior nucleus of the thalamus (ANT-DBS) is an established therapy for temporal lobe epilepsy. However, the optimal stimulation parameters and their impact on memory, mood and sleep comorbidities remain unclear. We used an investigational brain sensing-stimulation implanted device to accurately track seizures, interictal epileptiform spikes (IES), and memory, mood and sleep comorbidities in five ambulatory subjects. Wireless streaming of limbic network local field potentials (LFPs) and subject behaviour were captured on a mobile device integrated with a cloud environment. Automated algorithms applied to the continuous LFPs were used to accurately cataloged seizures, IES and sleep-wake brain state. Memory and mood assessments were remotely administered to densely sample cognitive and behavioural response during ANT-DBS in ambulatory subjects living in their natural home environment. We evaluated the effect of continuous low-frequency and duty cycle high-frequency ANT-DBS on epileptiform activity and memory, mood and sleep comorbidities. Both low-frequency and high-frequency ANT-DBS paradigms reduced seizures. However, continuous low-frequency ANT-DBS showed greater reductions in IES, electrographic seizures and better sleep and memory outcomes. These results highlight the potential of synchronized brain sensing and dense behavioural tracking during ANT-DBS for optimizing neuromodulation therapy. While studies with larger patient numbers are needed to validate the benefits of low-frequency ANT-DBS, these findings are potentially translatable to individuals currently implanted with ANT-DBS systems.

OBJECTIVE Stereotactic radiosurgery (SRS) offers excellent tumor control for pituitary adenoma (PA); however, treatment failure occasionally necessitates salvage surgery. Comprehensive studies on salvage surgical outcomes for recurrent PA after SRS remain scarce. This study aimed to elucidate the outcomes of salvage endonasal transsphenoidal surgery (sETS) for progressive PA failing SRS. METHODS This retrospective, two institution–based cohort study analyzed data from patients who underwent sETS for progressive PA failing SRS. Progression-free survival (PFS), disease-specific survival (DSS), and neurological and endocrinological outcomes in the sETS group were analyzed and compared with those in the primary ETS (pETS) group after propensity score matching using the following variables: age at surgery, maximum tumor diameter, highest Knosp–Steiner classification, and tumor type. RESULTS Thirteen sETS patients (8 males [62%], median age at surgery of 56 years) with 5 nonfunctioning (39%), 6 corticotropic (46%), and 2 other functioning (15%) PAs who received median (range) follow-up of 125 ( 23–169) months were included. None of the patients experienced new neurological deficits or death after sETS. The median (range) tumor resection rate was 90% (80%–100%). The 5-year PFS and DSS rates were 55% and 77%, respectively. All 4 patients (31%) who experienced recurrence after sETS had corticotropic tumors. In the matched cohort analysis between the sETS group with 12 patients and the pETS group with 12 patients, no significant differences were observed in surgical outcomes. PFS rates were marginally higher in the sETS group than in the pETS group (80% vs 49% at 3 years, p = 0.216, log-rank test), and DSS was similar between the two groups (p = 0.543, log-rank test). CONCLUSIONS The authors’ results indicate that ETS can be safely performed as a salvage treatment after failed SRS with low complication rates and satisfactory tumor control in treatment-resistant PA.

Abstract To propose a novel entity of possible intraosseous pseudoprogression in clival chordoma following proton radiation therapy (PRT). A total of 38 consecutive patients who underwent surgical resection followed by PRT for clival chordoma between January 2015 and December 2023 were analyzed retrospectively. Follow-up magnetic resonance imaging (MRI) suggesting recurrence or progression was evaluated for validity. Apparent diffusion coefficient (ADC) and tumor-to-brainstem signal intensity ratio on contrast-enhanced T1-weighted imaging (Rce) were assessed. Pseudoprogression was defined as (1) MRI signs of recurrence or progression with no pathological confirmation despite obtaining a specimen, or (2) MRI signs of recurrence or regression with spontaneous resolution/regression. Of the 11 patients with MRI findings suggestive of recurrence or progression, 3 were diagnosed with recurrence, 5 with progression, and 3 with pseudoprogression. Patients with pseudoprogression were significantly younger than those with progression (p = 0.04), and all were female. The median time to recurrence, progression, and pseudoprogression was 31, 29, and 21 months, respectively. The three pseudoprogression cases were managed with gross-total resection followed by stereotactic radiosurgery, extensive biopsy, and observation, respectively. Although statistical significance was not reached, ADC (p = 0.33) and Rce (p = 0.13) tended to be higher in pseudoprogression cases. After PRT for clival chordoma, intraosseous pseudoprogression should be considered in the differential diagnosis, particularly in relatively young female patients, although the role of ADC and Rce on MRI remains inconclusive. Multidisciplinary teams managing chordomas should take this into account when determining the aggressiveness of treatment in such cases.