Genetic and phenotypic characterization of Parkinson's disease at the clinic-wide level.

Observational studies in Parkinson's disease (PD) deeply characterize relatively small numbers of participants. The Molecular Integration in Neurological Diagnosis Initiative seeks to characterize molecular and clinical features of every PD patient at the University of Pennsylvania (UPenn). The objectives of this study are to determine the feasibility of genetic characterization in PD and assess clinical features by sex and GBA1/LRRK2 status on a clinic-wide scale. All PD patients with clinical visits at the UPenn PD Center between 9/2018 and 12/2022 were eligible. Blood or saliva were collected, and a clinical questionnaire administered. Genotyping at 14 GBA1 and 8 LRRK2 variants was performed. PD symptoms were compared by sex and gene groups. 2063 patients were approached and 1,689 (82%) were enrolled, with 374 (18%) declining to participate. 608 (36%) females were enrolled, 159 (9%) carried a GBA1 variant, and 44 (3%) carried a LRRK2 variant. Compared with males, females across gene groups more frequently reported dystonia (53% vs 46%, p = 0.01) and anxiety (64% vs 55%, p < 0.01), but less frequently reported cognitive impairment (10% vs 49%, p < 0.01) and vivid dreaming (53% vs 60%, p = 0.01). GBA1 variant carriers more frequently reported anxiety (67% vs 57%, p = 0.04) and depression (62% vs 46%, p < 0.01) than non-carriers; LRRK2 variant carriers did not differ from non-carriers. We report feasibility for near-clinic-wide enrollment and characterization of individuals with PD during clinical visits at a high-volume academic center. Clinical symptoms differ by sex and GBA1, but not LRRK2, status.

Selective Posterior Cerebral Artery Wada Better Predicts Good Memory and Naming Outcomes Following Selective Stereotactic Thermal Ablation for Medial Temporal Lobe Epilepsy Than Internal Carotid Artery Wada.

The conventional intracarotid amobarbital (Wada) test has been used to assess memory function in patients being considered for temporal lobe epilepsy (TLE) surgery. Minimally invasive approaches that target the medial temporal lobe (MTL) and spare neocortex are increasingly used, but a knowledge gap remains in how to assess memory and language risk from these procedures. We retrospectively compared results of two versions of the Wada test, the intracarotid artery (ICA-Wada) and posterior cerebral artery (PCA-Wada) approaches, with respect to predicting subsequent memory and language outcomes, particularly after stereotactic laser amygdalohippocampotomy (SLAH). We included all patients being considered for SLAH who underwent both ICA-Wada and PCA-Wada at a single institution. Memory and confrontation naming assessments were conducted using standardized neuropsychological tests to assess pre- to post-surgical changes in cognitive performance. Of 13 patients who initially failed the ICA-Wada, only one patient subsequently failed the PCA-Wada (p=0.003, two-sided binomial test with p 0 =0.5) demonstrating that these tests assess different brain regions or networks. PCA-Wada had a high negative predictive value for the safety of SLAH, compared to ICA-Wada, as none of the patients who underwent SLAH after passing the PCA-Wada experienced catastrophic memory decline (0 of 9 subjects, p <.004, two-sided binomial test with p 0 =0.5), and all experienced a good cognitive outcome. In contrast, the single patient who received a left anterior temporal lobectomy after failed ICA- and passed PCA-Wada experienced a persistent, near catastrophic memory decline. On confrontation naming, few patients exhibited disturbance during the PCA-Wada. Following surgery, SLAH patients showed no naming decline, while open resection patients, whose surgeries all included ipsilateral temporal lobe neocortex, experienced significant naming difficulties (Fisher's exact test, p <.05). These findings demonstrate that (1) failing the ICA-Wada falsely predicts memory decline following SLAH, (2) PCA-Wada better predicts good memory outcomes of SLAH for MTLE, and (3) the MTL brain structures affected by both PCA-Wada and SLAH are not directly involved in language processing.

A biological definition of neuronal α-synuclein disease: towards an integrated staging system for research.

Parkinson's disease and dementia with Lewy bodies are currently defined by their clinical features, with α-synuclein pathology as the gold standard to establish the definitive diagnosis. We propose that, given biomarker advances enabling accurate detection of pathological α-synuclein (ie, misfolded and aggregated) in CSF using the seed amplification assay, it is time to redefine Parkinson's disease and dementia with Lewy bodies as neuronal α-synuclein disease rather than as clinical syndromes. This major shift from a clinical to a biological definition of Parkinson's disease and dementia with Lewy bodies takes advantage of the availability of tools to assess the gold standard for diagnosis of neuronal α-synuclein (n-αsyn) in human beings during life. Neuronal α-synuclein disease is defined by the presence of pathological n-αsyn species detected in vivo (S; the first biological anchor) regardless of the presence of any specific clinical syndrome. On the basis of this definition, we propose that individuals with pathological n-αsyn aggregates are at risk for dopaminergic neuronal dysfunction (D; the second biological anchor). Our biological definition establishes a staging system, the neuronal α-synuclein disease integrated staging system (NSD-ISS), rooted in the biological anchors (S and D) and the degree of functional impairment caused by clinical signs or symptoms. Stages 0-1 occur without signs or symptoms and are defined by the presence of pathogenic variants in the SNCA gene (stage 0), S alone (stage 1A), or S and D (stage 1B). The presence of clinical manifestations marks the transition to stage 2 and beyond. Stage 2 is characterised by subtle signs or symptoms but without functional impairment. Stages 2B-6 require both S and D and stage-specific increases in functional impairment. A biological definition of neuronal α-synuclein disease and an NSD-ISS research framework are essential to enable interventional trials at early disease stages. The NSD-ISS will evolve to include the incorporation of data-driven definitions of stage-specific functional anchors and additional biomarkers as they emerge and are validated. Presently, the NSD-ISS is intended for research use only; its application in the clinical setting is premature and inappropriate.

Seizure event detection using intravital two-photon calcium imaging data.

Significance: Intravital cellular calcium imaging has emerged as a powerful tool to investigate how different types of neurons interact at the microcircuit level to produce seizure activity, with newfound potential to understand epilepsy. Although many methods exist to measure seizure-related activity in traditional electrophysiology, few yet exist for calcium imaging. Aim: To demonstrate an automated algorithmic framework to detect seizure-related events using calcium imaging-including the detection of pre-ictal spike events, propagation of the seizure wavefront, and terminal spreading waves for both population-level activity and that of individual cells. Approach: We developed an algorithm for precise recruitment detection of population and individual cells during seizure-associated events, which broadly leverages averaged population activity and high-magnitude slope features to detect single-cell pre-ictal spike and seizure recruitment. We applied this method to data recorded using awake in vivo two-photon calcium imaging during pentylenetetrazol-induced seizures in mice. Results: We demonstrate that our detected recruitment times are concordant with visually identified labels provided by an expert reviewer and are sufficiently accurate to model the spatiotemporal progression of seizure-associated traveling waves. Conclusions: Our algorithm enables accurate cell recruitment detection and will serve as a useful tool for researchers investigating seizure dynamics using calcium imaging.

Seizure Event Detection Using Intravital Two-Photon Calcium Imaging Data.

Significance: Genetic cellular calcium imaging has emerged as a powerful tool to investigate how different types of neurons interact at the microcircuit level to produce seizure activity, with newfound potential to understand epilepsy. Although many methods exist to measure seizure-related activity in traditional electrophysiology, few yet exist for calcium imaging. Aim: To demonstrate an automated algorithmic framework to detect seizure-related events using calcium imaging - including the detection of pre-ictal spike events, propagation of the seizure wavefront, and terminal spreading waves for both population-level activity and that of individual cells. Approach: We developed an algorithm for precise recruitment detection of population and individual cells during seizure-associated events, which broadly leverages averaged population activity and high-magnitude slope features to detect single-cell pre-ictal spike and seizure recruitment. We applied this method to data recorded using awake in vivo two-photon calcium imaging during pentylenetetrazol induced seizures in mice. Results: We demonstrate that our detected recruitment times are concordant with visually identified labels provided by an expert reviewer and are sufficiently accurate to model the spatiotemporal progression of seizure-associated traveling waves. Conclusions: Our algorithm enables accurate cell recruitment detection and will serve as a useful tool for researchers investigating seizure dynamics using calcium imaging.

Risk Factors Associated With Atrial Fibrillation in Elderly Patients.

Background: Atrial fibrillation (AF) is the most common arrhythmia with a growing prevalence worldwide, especially in the elderly population. Patients with AF are at higher risk of serious life-threatening events and complications that may lead to long-term sequelae and reduce quality of life. The aim of our study was to examine the association of additional risk factors and comorbid medical conditions with AF in patients 65 years, or older. Methods: We performed a retrospective electronic medical record review of patients aged 65 years and older, who visited our internal medicine office between July 1, 2020 and June 30, 2021. Results: Among 2,433 patients, 418 patients (17.2%) had AF. Our analysis showed that for each unit increased in age, there was a 4.5% increase in the odds of AF (95% confidence interval (CI) 2.2-6.9%; P < 0.001). Compared to patients of Caucasian descent, African-American patients had significantly decreased odds of AF (odds ratio (OR) 0.274, 95% CI 0.141 - 0.531; P < 0.001). Patients with hypertension had 2.241 greater odds of AF (95% CI 1.421 - 3.534; P = 0.001). Additional comorbidities with significantly greater odds of AF included other cardiac arrhythmias (OR 2.523, 95% CI 1.720 - 3.720; P < 0.001), congestive heart failure (OR 3.111, 95% CI 1.674 - 5.784; P < 0.001), osteoarthritis (OR 3.014, 95% CI 2.138 - 4.247; P < 0.001), liver disease (OR 2.129, 95% CI 1.164 - 3.893; P = 0.014), and colorectal disease (OR 1.500 95% CI 1.003 - 2.243; P = 0.048). Comorbidities with significantly decreased odds of AF included other rheumatological disorder (OR 0.144, 95% CI 0.086 - 0.243; P < 0.001), non-steroidal anti-inflammatory drugs (NSAIDs) use (OR 0.206, 95% CI 0.125 - 0.338; P < 0.001), and corticosteroid use (OR 0.553, 95% CI 0.374 - 0.819; P = 0.003). Conclusions: Increasing age, hypertension, presence of other cardiac arrhythmias, congestive heart failure, osteoarthritis, liver disease, and colorectal disease are associated with increased odds of having AF.

A Faculty-Led, Community-Building Program That Enhances Student-Faculty Connections within Biology.

Connections between students and faculty on campus may influence students' sense of belonging, and a greater sense of belonging has a positive effect on student success. We developed a low-cost, faculty-led program of community-building events and implemented the program in the biology department at a small liberal-arts institution with the goal of improving students' sense of community. Student responses to surveys indicated that the majority of students felt connected to faculty and students in the department; however, Black or African American students initially felt a lower level of connection to faculty than did white students. After implementing our series of community-building events, students surveyed reported high levels of satisfaction with the events. Furthermore, there was a trend toward a higher percentage of Black or African American students than white students reporting that they were more likely to reach out to faculty after participating in the community-building events. Thus, our low-cost program improved connections between students and faculty in the biology department. Collectively, our results suggest that academic departments can implement community-building programs to improve students' sense of belonging.

Bioluminescence-Optogenetics: A Practical Guide.

Manipulation of neural activity in genetically predefined populations of neurons through genetic techniques is an essential tool in the field of neuroscience as well as a potential avenue in treating a vast assortment of neurological and psychiatric diseases. Here, we describe an emerging methodology of molecular neuromodulation termed bioluminescence-optogenetics (BL-OG) where BL is harnessed to activate bacterial light-driven channels and pumps expressed in neurons to control their activity. BL-OG is realized through opsin-luciferase fusion proteins called luminopsins (LMOs). In this chapter, we will provide a practical guide for applying BL-OG and LMOs in vitro using a cell line and primary cells in culture. In the following chapter, we will turn our focus towards BL-OG applications in ex vivo and in vivo rodent models of the nervous system.

Applications of Bioluminescence-Optogenetics in Rodent Models.

In the preceding chapter, we introduced bioluminescence-optogenetics (BL-OG) and luminopsin fusion proteins (LMOs), an emerging method of molecular neuromodulation. In addition to reviewing the fundamental principles of BL-OG, we provided a discussion of its application in vitro, including with cell lines and primary cells in culture in vitro. BL-OG is mediated by an easily diffusible molecule, luciferin, and when applied systemically in rodents, the substrate can spread throughout the body, including the brain, achieving powerful molecular neuromodulation with convenience even in awake and behaving animals. In this chapter, we provide a practical guide for BL-OG and LMO applications in rodent models of the nervous system, both ex vivo and in vivo.

Predictors of multi-domain cognitive decline following DBS for treatment of Parkinson's disease.

BACKGROUND: Statistically and clinically significant cognitive declines are observed in a small subset of individuals with Parkinson's Disease (PD) following treatment with Deep Brain Stimulation (DBS). OBJECTIVES: We examine the association between multi-domain cognitive decline (MCD) and demographic and baseline clinical variables and the incidence of serious adverse events (SAE) arising within a six-month interval following DBS for PD. METHOD: Study participants with PD who displayed MCD at 6-month follow-up evaluation after DBS (n = 18) were contrasted with individuals with PD from the same study who did not show cognitive decline after DBS (n = 146). Logistic regression analyses were employed to assess relationship between predictors, including age (>70 years old), pre-DBS cognitive screening test performance, SAE, and MCD. MCD+ and MCD-groups were also compared on other baseline clinical and demographic variables. RESULTS: MCD showed modest association with older age and lower baseline neurocognitive screening performance, whereas the groups did not differ on most other baseline clinical and demographic variables. SAEs during the study interval were the most robust predictor of MCD in the DBS group. A variety of SAEs were documented in study participants experiencing MCD after DBS surgery, including, but not limited to, infections and small intracranial hemorrhages. CONCLUSIONS: Older age and lower baseline cognition measured prior to treatment are associated with MCD measured at six-months after DBS. SAE occurring following DBS surgery are also predictive of MCD. These predictors may reflect aspects of "frailty" in advanced PD. Risk factors for SAE warrant careful consideration in clinical trials.

Small-diameter artery decellularization: Effects of anionic detergent concentration and treatment duration on porcine internal thoracic arteries.

Engineered replacement materials have tremendous potential for vascular applications where over 400,000 damaged and diseased blood vessels are replaced annually in the United States alone. Unlike large diameter blood vessels, which are effectively replaced by synthetic materials, prosthetic small-diameter vessels are prone to early failure, restenosis, and reintervention surgery. We investigated the differential response of varying 0%-6% sodium dodecyl sulfate and sodium deoxycholate anionic detergent concentrations after 24 and 72 h in the presence of DNase using biochemical, histological, and biaxial mechanical analyses to optimize the decellularization process for xenogeneic vascular tissue sources, specifically the porcine internal thoracic artery (ITA). Detergent concentrations greater than 1% were successful at removing cytoplasmic and cell surface proteins but not DNA content after 24 h. A progressive increase in porosity and decrease in glycosaminoglycan (GAG) content was observed with detergent concentration. Augmented porosity was likely due to the removal of both cells and GAGs and could influence recellularization strategies. The treatment duration on the other hand, significantly improved decellularization by reducing DNA content to trace amounts after 72 h. Prolonged treatment times reduced laminin content and influenced the vessel's mechanical behavior in terms of altered circumferential stress and stretch while further increasing porosity. Collectively, DNase with 1% detergent for 72 h provided an effective and efficient decellularization strategy to be employed in the preparation of porcine ITAs as bypass graft scaffolding materials with minor biomechanical and histological penalties.

Impairment of visual cortical plasticity by amyloid-beta species.

INTRODUCTION: A variety of transgenic and knock-in mice that express mutant alleles of Amyloid precursor protein (APP) have been used to model the effects of amyloid-beta (Aß) on circuit function in Alzheimer's disease (AD); however phenotypes described in these mice may be affected by expression of mutant APP or proteolytic cleavage products independent of Aß. In addition, the effects of mutant APP expression are attributed to elevated expression of the amyloidogenic, 42-amino acid-long species of Aß (Aß42) associated with amyloid plaque accumulation in AD, though elevated concentrations of Aß40, an Aß species produced with normal synaptic activity, may also affect neural function. METHODS: To explore the effects of elevated expression of Aß on synaptic function in vivo, we assessed visual system plasticity in transgenic mice that express and secrete Aß throughout the brain in the absence of APP overexpression. Transgenic mice that express either Aß40 or Aß42 were assayed for their ability to appropriately demonstrate ocular dominance plasticity following monocular deprivation. RESULTS: Using two complementary approaches to measure the plastic response to monocular deprivation, we find that male and female mice that express either 40- or 42-amino acid-long Aß species demonstrate a plasticity defect comparable to that elicited in transgenic mice that express mutant alleles of APP and Presenilin 1 (APP/PS1 mice). CONCLUSIONS: These data support the hypothesis that mutant APP-driven plasticity impairment in mouse models of AD is mediated by production and accumulation of Aß. Moreover, these findings suggest that soluble species of Aß are capable of modulating synaptic plasticity, likely independent of any aggregation. These findings may have implications for the role of soluble species of Aß in both development and disease settings.

Bioluminescence-Optogenetics.

In this chapter, we introduce a relatively new, emerging method for molecular neuromodulation-bioluminescence-optogenetics. Bioluminescence-optogenetics is mediated by luminopsin fusion proteins-light-sensing opsins fused to light-emitting luciferases. We describe their structures and working mechanisms and discuss their unique benefits over conventional optogenetics and chemogenetics. We also summarize applications of bioluminescence-optogenetics in various neurological disease models in rodents.

Whole Clinic Research Enrollment in Parkinson's Disease: The Molecular Integration in Neurological Diagnosis (MIND) Study.

BACKGROUND: Observational studies in Parkinson's disease (PD) have focused on relatively small numbers of research participants who are studied extensively. The Molecular Integration in Neurological Diagnosis Initiative at the University of Pennsylvania aims to characterize molecular and clinical features of PD in every patient in a large academic center. OBJECTIVE: To determine the feasibility and interest in a global-capture biomarker research protocol. Additionally, to describe the clinical characteristics and GBA and LRRK2 variant carrier status among participants. METHODS: All patients at UPenn with a clinical diagnosis of PD were eligible. Informed consent included options for access to the medical record, future recontact, and use of biosamples for additional studies. A blood sample and a completed questionnaire were obtained from participants. Targeted genotyping for four GBA and eight LRRK2 variants was performed, with plasma and DNA banked for future research. RESULTS: Between September 2018 and December 2019, 704 PD patients were approached for enrollment; 652 (92.6%) enrolled, 28 (3.97%) declined, and 24 (3.41%) did not meet eligibility criteria. Median age was 69 (IQR 63_75) years, disease duration was 5.41 (IQR 2.49_9.95) years, and 11.10%of the cohort was non-white. Disease risk-associated variants in GBA were identified in 39 participants (5.98%) and in LRRK2 in 16 participants (2.45%). CONCLUSIONS: We report the clinical and genetic characteristics of PD patients in an all-comers, global capture protocol from an academic center. Patient interest in participation and yield for identification of GBA and LRRK2 mutation carriers is high, demonstrating feasibility of PD clinic-wide molecular characterization.

Radiofrequency Ablation Through Previously Effective Deep Brain Stimulation Leads for Parkinson Disease: A Retrospective Series.

BACKGROUND: Although deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) is the surgical method of choice to treat the canonical symptoms of Parkinson disease, occasionally surgical sites become infected or the hardware erodes, necessitating explantation. Usual practice is to remove and reimplant replacement leads after tissue healing, leaving patients without the clinical benefits of DBS for several months, and at risk for DBS withdrawal in some, and some patients are no longer good surgical candidates for reimplantation. Radiofrequency ablation through the DBS lead is an option for these patients. METHODS: We performed a retrospective chart review of all patients who underwent radiofrequency ablation of the STN or GPi through indwelling DBS leads performed before hardware removal at our institution. We generated patient-specific anatomic models to determine lesion locations and volumes. RESULTS: Six patients underwent radiofrequency ablation of the STN (n = 4) and GPi (n = 2) through indwelling DBS leads. All 6 of these patients initially showed comparable motor symptom relief to that experienced with DBS before lesioning, with 4 patients sustaining meaningful long-term (≥2 years) improvement. Better outcomes were achieved in those patients with a higher percentage of the planned target lesioned. CONCLUSIONS: Radiofrequency ablation through indwelling DBS leads before explantation could be considered a viable alternative to subsequent reimplantation or stereotactic lesion in patients with Parkinson disease in whom hardware explantation is necessary, if the patient achieved substantive symptom relief with DBS. This approach avoids symptom exacerbation while awaiting revision surgery.

Clinical and Imaging Progression in the PARS Cohort: Long-Term Follow-up.

BACKGROUND AND OBJECTIVES: The PARS (Parkinson Associated Risk Syndrome) study was designed to test whether screening for hyposmia followed by dopamine transporter imaging can identify risk for conversion to clinical PD, and to evaluate progression markers during the prodromal period. METHODS: Subjects with hyposmia completed annual clinical evaluations and biennial [123 I]ß-CIT single-photon emission computed tomography scans. Subjects were categorized as normal (>80% age-expected tracer uptake; n = 134), indeterminate (>65-80%; n = 30), and dopamine transporter deficit (≤65%; n = 21) by their baseline scan, and survival analysis was used to compare risk of conversion to motor PD. Progressing to a scan with a dopamine transporter deficit was assessed for those subjects with either normal or indeterminate baseline imaging. RESULTS: Over a mean of 6.3 [standard deviation: 2.2] years of follow-up, 67% (n = 14) of dopamine transporter deficit subjects, 20% (n = 6) of dopamine transporter indeterminate subjects, and 4% (n = 6) of dopamine transporter normal subjects converted to a PD diagnosis (P < 0.0001). Among subjects without dopamine transporter deficit at baseline, a reduction to ≤65% age-expected uptake occurred in 12 of 30 (40%) with indeterminate dopamine transporter and 7 of 134 (5%) with no dopamine transporter DAT deficit (P < 0.0001). Imaging conversion during follow-up was associated with subsequent clinical conversion (hazard ratio: 9.6; P = 0.0157). DISCUSSION AND CONCLUSIONS: Long-term follow-up of the PARS cohort demonstrated a high rate of conversion to clinical PD in subjects who either had abnormal dopamine transporter imaging at baseline or developed abnormal imaging during follow-up. These data extend the earlier PARS findings and present new results showing the sequence of incident imaging deficit, imaging progression, and clinical changes that occur in prodromal PD. © 2020 International Parkinson and Movement Disorder Society.

Spectral and Entropic Features Are Altered by Age in the Electroencephalogram in Patients under Sevoflurane Anesthesia.

BACKGROUND: Preexisting factors such as age and cognitive performance can influence the electroencephalogram (EEG) during general anesthesia. Specifically, spectral EEG power is lower in elderly, compared to younger, subjects. Here, the authors investigate age-related changes in EEG architecture in patients undergoing general anesthesia through a detailed examination of spectral and entropic measures. METHODS: The authors retrospectively studied 180 frontal EEG recordings from patients undergoing general anesthesia, induced with propofol/fentanyl and maintained by sevoflurane at the Waikato Hospital in Hamilton, New Zealand. The authors calculated power spectral density and normalized power spectral density, the entropic measures approximate and permutation entropy, as well as the beta ratio and spectral entropy as exemplary parameters used in current monitoring systems from segments of EEG obtained before the onset of surgery (i.e., with no noxious stimulation). RESULTS: The oldest quartile of patients had significantly lower 1/f characteristics (P < 0.001; area under the receiver operating characteristics curve, 0.84 [0.76 0.92]), indicative of a more uniform distribution of spectral power. Analysis of the normalized power spectral density revealed no significant impact of age on relative alpha (P = 0.693; area under the receiver operating characteristics curve, 0.52 [0.41 0.63]) and a significant but weak effect on relative beta power (P = 0.041; area under the receiver operating characteristics curve, 0.62 [0.52 0.73]). Using entropic parameters, the authors found a significant age-related change toward a more irregular and unpredictable EEG (permutation entropy: P < 0.001, area under the receiver operating characteristics curve, 0.81 [0.71 0.90]; approximate entropy: P < 0.001; area under the receiver operating characteristics curve, 0.76 [0.66 0.85]). With approximate entropy, the authors could also detect an age-induced change in alpha-band activity (P = 0.002; area under the receiver operating characteristics curve, 0.69 [0.60 78]). CONCLUSIONS: Like the sleep literature, spectral and entropic EEG features under general anesthesia change with age revealing a shift toward a faster, more irregular, oscillatory composition of the EEG in older patients. Age-related changes in neurophysiological activity may underlie these findings however the contribution of age-related changes in filtering properties or the signal to noise ratio must also be considered. Regardless, most current EEG technology used to guide anesthetic management focus on spectral features, and improvements to these devices might involve integration of entropic features of the raw EEG.

Safety and effectiveness of stereotactic laser ablation for epileptogenic cerebral cavernous malformations.

OBJECTIVE: Magnetic resonance (MR) thermography-guided laser interstitial thermal therapy, or stereotactic laser ablation (SLA), is a minimally invasive alternative to open surgery for focal epilepsy caused by cerebral cavernous malformations (CCMs). We examined the safety and effectiveness of SLA of epileptogenic CCMs. METHODS: We retrospectively analyzed 19 consecutive patients who presented with focal seizures associated with a CCM. Each patient underwent SLA of the CCM and adjacent cortex followed by standard clinical and imaging follow-up. RESULTS: All but one patient had chronic medically refractory epilepsy (median duration 8 years, range 0.5-52 years). Lesions were located in the temporal (13), frontal (five), and parietal (one) lobes. CCMs induced magnetic susceptibility artifacts during thermometry, but perilesional cortex was easily visualized. Fourteen of 17 patients (82%) with >12 months of follow-up achieved Engel class I outcomes, of which 10 (59%) were Engel class IA. Two patients who were not seizure-free from SLA alone became so following intracranial electrode-guided open resection. Delayed postsurgical imaging validated CCM involution (median 83% volume reduction) and ablation of surrounding cortex. Histopathologic examination of one previously ablated CCM following open surgery confirmed obliteration. SLA caused no detectable hemorrhages. Two symptomatic neurologic deficits (visual and motor) were predictable, and neither was permanently disabling. SIGNIFICANCE: In a consecutive retrospective series, MR thermography-guided SLA was an effective alternative to open surgery for epileptogenic CCM. The approach was free of hemorrhagic complications, and clinically significant neurologic deficits were predictable. SLA presents no barrier to subsequent open surgery when needed.