Unifying biophysical consciousness theories with MaxCon: maximizing configurations of brain connectivity.

There is such a vast proliferation of scientific theories of consciousness that it is worrying some scholars. There are even competitions to test different theories, and the results are inconclusive. Consciousness research, far from converging toward a unifying framework, is becoming more discordant than ever, especially with respect to theoretical elements that do not have a clear neurobiological basis. Rather than dueling theories, an integration across theories is needed to facilitate a comprehensive view on consciousness and on how normal nervous system dynamics can develop into pathological states. In dealing with what is considered an extremely complex matter, we try to adopt a perspective from which the subject appears in relative simplicity. Grounded in experimental and theoretical observations, we advance an encompassing biophysical theory, MaxCon, which incorporates aspects of several of the main existing neuroscientific consciousness theories, finding convergence points in an attempt to simplify and to understand how cellular collective activity is organized to fulfill the dynamic requirements of the diverse theories our proposal comprises. Moreover, a computable index indicating consciousness level is presented. Derived from the level of description of the interactions among cell networks, our proposal highlights the association of consciousness with maximization of the number of configurations of neural network connections -constrained by neuroanatomy, biophysics and the environment- that is common to all consciousness theories.

Wavelet phase coherence of ictal scalp EEG-extracted muscle activity (SMA) as a biomarker for sudden unexpected death in epilepsy (SUDEP).

OBJECTIVE: Approximately 50 million people worldwide have epilepsy and 8-17% of the deaths in patients with epilepsy are attributed to sudden unexpected death in epilepsy (SUDEP). The goal of the present work was to establish a biomarker for SUDEP so that preventive treatment can be instituted. APPROACH: Seizure activity in patients with SUDEP and non-SUDEP was analyzed, specifically, the scalp EEG extracted muscle activity (SMA) and the average wavelet phase coherence (WPC) during seizures was computed for two frequency ranges (1-12 Hz, 13-30 Hz) to identify differences between the two groups. MAIN RESULTS: Ictal SMA in SUDEP patients showed a statistically higher average WPC value when compared to non-SUDEP patients for both frequency ranges. Area under curve for a cross-validated logistic classifier was 81%. SIGNIFICANCE: Average WPC of ictal SMA is a candidate biomarker for early detection of SUDEP.

Slow wave sleep is associated with forgetting in patients with temporal lobe epilepsy.

While time spent in slow wave sleep (SWS) after learning promotes memory consolidation in the healthy brain, it is unclear if the same benefit is obtained in patients with temporal lobe epilepsy (TLE). Interictal epileptiform discharges (IEDs) are potentiated during SWS and thus may disrupt memory consolidation processes thought to depend on hippocampal-neocortical interactions. Here, we explored the relationship between SWS, IEDs, and overnight forgetting in patients with TLE. Nineteen patients with TLE studied object-scene pairs and memory was tested across a day of wakefulness (6 hrs) and across a night of sleep (16 hrs) while undergoing continuous scalp EEG monitoring. We found that time spent in SWS after learning was related to greater forgetting overnight. Longer duration in SWS and number of IEDs were each associated with greater forgetting, although the number of IEDs did not mediate the relationship between SWS and memory. Further research, particularly with intracranial recordings, is required to identify the mechanisms by which SWS and IEDs can be pathological to sleep-dependent memory consolidation in patients with TLE.

18F-Flortaucipir (AV1451) imaging identifies grey matter atrophy in retired athletes.

BACKGROUND: The long-term consequences of concussions may include pathological neurodegeneration as seen in Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE). Tau-PET showed promise as a method to detect tau pathology of CTE, but more studies are needed OBJECTIVE: This study aimed (1) to assess the association of imaging evidence of tau pathology with brain volumes in retired athletes and (2) to examine the relationship between tau-PET and neuropsychological functioning. METHODS: Former contact sport athletes were recruited through the Canadian Football League Alumni Association or the Canadian Concussion Centre clinic. Athletes completed MRI, [18F]flortaucipir tau-PET, and a neuropsychological battery. Memory composite was created by averaging the Rey Auditory Verbal Learning Test and Rey Visual Design Learning Test z-scores. Grey matter (GM) volumes were age/intracranial volume corrected using normal control MRIs. Tau-PET % positivity in GM was calculated as the number of positive voxels (≥ 1.3 standardized uptake value ratio (SUVR)/total voxels). RESULTS: 47 retired contact sport athletes negative for AD (age:51 ± 14; concussions/athlete:15 ± 2) and 54 normal controls (age:50 ± 13) were included. Tau-PET positive voxels had significantly lower GM volumes, compared to tau-PET negative voxels (- 0.37 ± 0.41 vs. - 0.31 ± 0.37, paired p = .006). There was a significant relationship between GM tau-PET % positivity and memory composite score (r = - .366, p = .02), controlled for age, PET scanner, and PET scan duration. There was no relationship between tau-PET measures and concussion number, or years of sport played. CONCLUSION: A higher tau-PET signal was associated with reduced GM volumes and lower memory scores. Tau-PET may be useful for identifying those at risk for neurodegeneration.

Functional connectivity changes in neurodegenerative biomarker-positive athletes with repeated concussions.

Multimodal biomarkers may identify former contact sports athletes with repeated concussions and at risk for dementia. Our study aims to investigate whether biomarker evidence of neurodegeneration in former professional athletes with repetitive concussions (ExPro) is associated with worse cognition and mood/behavior, brain atrophy, and altered functional connectivity. Forty-one contact sports athletes with repeated concussions were divided into neurodegenerative biomarker-positive (n = 16) and biomarker-negative (n = 25) groups based on positivity of serum neurofilament light-chain. Six healthy controls (negative for biomarkers) with no history of concussions were also analyzed. We calculated cognitive and mood/behavior composite scores from neuropsychological assessments. Gray matter volume maps and functional connectivity of the default mode, salience, and frontoparietal networks were compared between groups using ANCOVAs, controlling for age, and total intracranial volume. The association between the connectivity networks and sports characteristics was analyzed by multiple regression analysis in all ExPro. Participants presented normal-range mean performance in executive function, memory, and mood/behavior tests. The ExPro groups did not differ in professional years played, age at first participation in contact sports, and number of concussions. There were no differences in gray matter volume between groups. The neurodegenerative biomarker-positive group had lower connectivity in the default mode network (DMN) compared to the healthy controls and the neurodegenerative biomarker-negative group. DMN disconnection was associated with increased number of concussions in all ExPro. Biomarkers of neurodegeneration may be useful to detect athletes that are still cognitively normal, but with functional connectivity alterations after concussions and at risk of dementia.

Acetazolamide as an effective treatment for pilomotor seizures in autoimmune encephalitis.

Pilomotor seizures are strongly associated with autoimmune encephalitis (AE), particularly anti-LGI1 encephalitis. The carbonic anhydrase inhibitor acetazolamide may have special efficacy for treating AE-associated pilomotor seizures. Six patients with AE (five anti-LGI1, one seronegative) and temporal lobe pilomotor seizures (five with seizures inducible by hyperventilation) were treated with acetazolamide, administered in a cycling (2-days-ON, 4-days-OFF) regimen to offset tolerance. Seizures were assessed during epilepsy monitoring unit (EMU) recordings in four inpatients (one of whom also maintained an outpatient seizure diary chronicling 1203 seizures over 1079 days); two outpatients self-reported seizure frequencies. The extended diary revealed an inverse correlation between acetazolamide and proportion of seizures/day: 6%, 2% (days 1, 2 ON); 3%, 13%, 31%, 45% (days 1, 2, 3, 4 OFF). This patient later developed focal status epilepticus upon wean of antiseizure medications during a seropositive AE relapse that was remarkably aborted with acetazolamide monotherapy. The other three EMU patients averaged .56 seizures/day ON, and 3.81 seizures/day OFF (p = .004). The two outpatients reported seizure reductions from 3-5/day to 2/week, and 15-20/day to none, respectively, after initiation of cycling acetazolamide. Likely related to cerebral CO2/pH sensitivity, acetazolamide can be unusually effective in controlling pilomotor seizures in AE, chronically or in acute settings.

Unusual combinations of neurodegenerative pathologies with chronic traumatic encephalopathy (CTE) complicates clinical prediction of CTE.

BACKGROUND AND PURPOSE: Chronic traumatic encephalopathy (CTE) has gained widespread attention due to its association with multiple concussions and contact sports. However, CTE remains a postmortem diagnosis, and the link between clinical symptoms and CTE pathology is poorly understood. This study aimed to investigate the presence of copathologies and their impact on symptoms in former contact sports athletes. METHODS: This was a retrospective case series design of 12 consecutive cases of former contact sports athletes referred for autopsy. Analyses are descriptive and include clinical history as well as the pathological findings of the autopsied brains. RESULTS: All participants had a history of multiple concussions, and all but one had documented progressive cognitive, psychiatric, and/or motor symptoms. The results showed that 11 of the 12 participants had evidence of CTE in the brain, but also other copathologies, including different combinations of tauopathies, and other rare entities. CONCLUSIONS: The heterogeneity of symptoms after repetitive head injuries and the diverse pathological combinations accompanying CTE complicate the prediction of CTE in clinical practice. It is prudent to consider the possibility of multiple copathologies when clinically assessing patients with repetitive head injuries, especially as they age, and attributing neurological or cognitive symptoms solely to presumptive CTE in elderly patients should be discouraged.

Touch-screen automatisms in the digital age.

OBJECTIVE: To describe a novel set of gestural automatisms related to the use of digital screens on smartphones and tablets in patients with epilepsy. METHODS: Representative patients were selected from among those admitted to the Epilepsy Monitoring Unit at the Toronto Western Hospital between April 2016 and January 2020, and included if they exhibited automatisms clearly related to or mimicking digital device use. RESULTS: In total 5 patients were included, 4 female. All had temporal lobe epilepsy: 2 had left mesial temporal sclerosis and 3 had normal imaging. Nearly equal numbers of seizures began with right (5/9) and left (4/9) temporal onsets, with most automatisms occurring after seizure propagation to bilateral temporal involvement (6/9). Left-handed automatisms were most common (8/9). The majority of the automatisms (7/9) were perseverative on device usage prior to the seizure. CONCLUSION: Gestural automatisms appear related to the contemporary lived experience, culture, and habitual behaviour of patients with epilepsy. In the modern era, the use of smartphones and tablets are both common and habitual for many, and this case series shows that touch-screen automatisms may be added to the semiological panoply of temporal lobe seizures.

Antenatal jaundice instruction and acute bilirubin encephalopathy in Nigeria.

BACKGROUND: Acute Bilirubin Encephalopathy (ABE) is common in Nigeria. Parents' inability to recognize jaundice and delays in seeking care are significant barriers to its prevention. METHODS: We compared associations of (1) interactive antenatal maternal jaundice instruction with postnatal reinforcement, (2) standard postnatal instruction, and (3) no maternal instruction with the incidence of ABE among 647 jaundice admissions stratified for risk factors identified in initial descriptive analysis. RESULTS: Eighty-three (83/647;12.8%) admissions developed ABE including eleven jaundice-related deaths. ABE was present at admission in 20/22 (90.9%) if mothers received no jaundice instruction and no antenatal care, 42/182 (23.1%) if received antenatal care but no instruction, 16/95 (16.8%) if received postnatal instruction only, and 4/337 (1.2%) if mothers received both antenatal and postnatal instruction (p < .001). ABE was highly associated with out-of-hospital delivery, number of antenatal clinic visits, and birth attendant, but these risks were mitigated by antenatal/postnatal instruction. Admission rates with bilirubin levels below treatment guidelines (12 mg/dL) were higher following instruction (30.7%) than with no instruction (14.4%). Limiting subjects to those meeting admission criteria increased ABE rates in all groups without altering conclusions. CONCLUSION: Interactive antenatal instruction with postnatal reinforcement resulted in timely care seeking and a lower incidence of ABE. IMPACT: Empowering mothers to participate in neonatal jaundice management is critical in low-income countries where jaundice monitoring and follow up are unreliable. Instructing mothers about jaundice in antenatal clinics with postnatal reinforcement is more effective than standard postpartum instruction in facilitating jaundice detection, timely care seeking, and lowering the incidence of acute bilirubin encephalopathy (ABE). Antenatal training also mitigates risks for ABE associated with out-of-hospital deliveries, limited antenatal care, and unskilled birth attendants. IMPACT: Adding structured jaundice instruction in antenatal clinics could greatly reduce bilirubin induced brain injury in countries where ABE is common.

Misfolded α-Synuclein in Cerebrospinal Fluid of Contact Sport Athletes.

BACKGROUND: Misfolded α-synuclein in Parkinson's disease (PD) and dementia with Lewy bodies (DLB) can be detected using the real-time quaking-induced conversion (RT-QuIC) technique in cerebrospinal fluid (CSF). OBJECTIVES: The objectives are (1) to examine misfolded CSF α-synuclein incidence, and (2) to compare clinical presentation, sports history, brain volumes, and RT-QuIC α-synuclein positivity in former athletes. METHODS: Thirty former athletes with magnetic resonance imaging, neuropsychological testing, and CSF analyzed for phosphorylated tau 181 (p-tau), total tau (t-tau), amyloid-ß 42 (Aß42), and neurofilament light chain (NfL). CSF α-synuclein was detected using RT-QuIC. RESULTS: Six (20%) former athletes were α-synuclein positive. α-Synuclein positive athletes were similar to α-synuclein negative athletes on demographics, sports history, clinical features, CSF p-tau, t-tau, Aß42, and NfL; however, had lower grey matter volumes in the right inferior orbitofrontal, right anterior insula and right olfactory cortices. CONCLUSIONS: α-Synuclein RT-QuIC analysis of CSF may be useful as a prodromal biofluid marker of PD and DLB. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Investigation of neurophysiologic and functional connectivity changes following glioma resection using magnetoencephalography.

Background: In patients with glioma, clinical manifestations of neural network disruption include behavioral changes, cognitive decline, and seizures. However, the extent of network recovery following surgery remains unclear. The aim of this study was to characterize the neurophysiologic and functional connectivity changes following glioma surgery using magnetoencephalography (MEG). Methods: Ten patients with newly diagnosed intra-axial brain tumors undergoing surgical resection were enrolled in the study and completed at least two MEG recordings (pre-operative and immediate post-operative). An additional post-operative recording 6-8 weeks following surgery was obtained for six patients. Resting-state MEG recordings from 28 healthy controls were used for network-based comparisons. MEG data processing involved artifact suppression, high-pass filtering, and source localization. Functional connectivity between parcellated brain regions was estimated using coherence values from 116 virtual channels. Statistical analysis involved standard parametric tests. Results: Distinct alterations in spectral power following tumor resection were observed, with at least three frequency bands affected across all study subjects. Tumor location-related changes were observed in specific frequency bands unique to each patient. Recovery of regional functional connectivity occurred following glioma resection, as determined by local coherence normalization. Changes in inter-regional functional connectivity were mapped across the brain, with comparable changes in low to mid gamma-associated functional connectivity noted in four patients. Conclusion: Our findings provide a framework for future studies to examine other network changes in glioma patients. We demonstrate an intrinsic capacity for neural network regeneration in the post-operative setting. Further work should be aimed at correlating neurophysiologic changes with individual patients' clinical outcomes.

Ipsilateral preictal alpha rhythm attenuation (IPARA): An EEG sign of side of seizure onset in temporal lobe epilepsy.

PURPOSE: Identification of the seizure onset zone is critically important for outlining the surgical plan in the treatment of pharmacoresistant focal epilepsy. In patients with temporal lobe epilepsy (TLE), bilateral ictal scalp EEG changes frequently occur and can make lateralization of the seizure onset zone difficult. We investigated the incidence and clinical utility of unilateral preictal alpha rhythm attenuation as a lateralizing sign of seizure onset in TLE. METHODS: Scalp EEG recordings of the seizures acquired during presurgical video-EEG monitoring of 57 consecutive patients with TLE were reviewed retrospectively. Included patients had interictal baseline recordings demonstrating symmetrical posterior alpha rhythm and seizures occurring during wakefulness. RESULTS: We identified a total of 649 seizures in the 57 patients, of which 448 seizures in 53 patients fulfilled the inclusion criteria. Among the 53 included patients, 7 patients (13.2%) exhibited a distinct attenuation of the posterior alpha rhythm prior to the first ictal EEG changes, in 26 of 112 (23.2%) included seizures. Preictal alpha rhythm attenuation in these seizures was ipsilateral to the ultimately determined side of seizure onset (based on video-EEG or intracranial EEG findings) in 22 (84.6%) of these seizures and bilateral in 4 (15.4%), and occurred on average 5.9 ± 2.6 s prior to ictal EEG onsets. CONCLUSION: Our findings suggest that in some patients with TLE lateralized preictal attenuation of the posterior alpha rhythm may be a useful indicator of side of seizure onset, presumably due to early disruption of thalamo-temporo-occipital network function, likely mediated through the thalamus.

Automated Interpretation of Clinical Electroencephalograms Using Artificial Intelligence.

Importance: Electroencephalograms (EEGs) are a fundamental evaluation in neurology but require special expertise unavailable in many regions of the world. Artificial intelligence (AI) has a potential for addressing these unmet needs. Previous AI models address only limited aspects of EEG interpretation such as distinguishing abnormal from normal or identifying epileptiform activity. A comprehensive, fully automated interpretation of routine EEG based on AI suitable for clinical practice is needed. Objective: To develop and validate an AI model (Standardized Computer-based Organized Reporting of EEG-Artificial Intelligence [SCORE-AI]) with the ability to distinguish abnormal from normal EEG recordings and to classify abnormal EEG recordings into categories relevant for clinical decision-making: epileptiform-focal, epileptiform-generalized, nonepileptiform-focal, and nonepileptiform-diffuse. Design, Setting, and Participants: In this multicenter diagnostic accuracy study, a convolutional neural network model, SCORE-AI, was developed and validated using EEGs recorded between 2014 and 2020. Data were analyzed from January 17, 2022, until November 14, 2022. A total of 30 493 recordings of patients referred for EEG were included into the development data set annotated by 17 experts. Patients aged more than 3 months and not critically ill were eligible. The SCORE-AI was validated using 3 independent test data sets: a multicenter data set of 100 representative EEGs evaluated by 11 experts, a single-center data set of 9785 EEGs evaluated by 14 experts, and for benchmarking with previously published AI models, a data set of 60 EEGs with external reference standard. No patients who met eligibility criteria were excluded. Main Outcomes and Measures: Diagnostic accuracy, sensitivity, and specificity compared with the experts and the external reference standard of patients' habitual clinical episodes obtained during video-EEG recording. Results: The characteristics of the EEG data sets include development data set (N = 30 493; 14 980 men; median age, 25.3 years [95% CI, 1.3-76.2 years]), multicenter test data set (N = 100; 61 men, median age, 25.8 years [95% CI, 4.1-85.5 years]), single-center test data set (N = 9785; 5168 men; median age, 35.4 years [95% CI, 0.6-87.4 years]), and test data set with external reference standard (N = 60; 27 men; median age, 36 years [95% CI, 3-75 years]). The SCORE-AI achieved high accuracy, with an area under the receiver operating characteristic curve between 0.89 and 0.96 for the different categories of EEG abnormalities, and performance similar to human experts. Benchmarking against 3 previously published AI models was limited to comparing detection of epileptiform abnormalities. The accuracy of SCORE-AI (88.3%; 95% CI, 79.2%-94.9%) was significantly higher than the 3 previously published models (P < .001) and similar to human experts. Conclusions and Relevance: In this study, SCORE-AI achieved human expert level performance in fully automated interpretation of routine EEGs. Application of SCORE-AI may improve diagnosis and patient care in underserved areas and improve efficiency and consistency in specialized epilepsy centers.

Ictal ECG-based assessment of sudden unexpected death in epilepsy.

Introduction: Previous case-control studies of sudden unexpected death in epilepsy (SUDEP) patients failed to identify ECG features (peri-ictal heart rate, heart rate variability, corrected QT interval, postictal heart rate recovery, and cardiac rhythm) predictive of SUDEP risk. This implied a need to derive novel metrics to assess SUDEP risk from ECG. Methods: We applied Single Spectrum Analysis and Independent Component Analysis (SSA-ICA) to remove artifact from ECG recordings. Then cross-frequency phase-phase coupling (PPC) was applied to a 20-s mid-seizure window and a contour of -3 dB coupling strength was determined. The contour centroid polar coordinates, amplitude (alpha) and angle (theta), were calculated. Association of alpha and theta with SUDEP was assessed and a logistic classifier for alpha was constructed. Results: Alpha was higher in SUDEP patients, compared to non-SUDEP patients (p < 0.001). Theta showed no significant difference between patient populations. The receiver operating characteristic (ROC) of a logistic classifier for alpha resulted in an area under the ROC curve (AUC) of 94% and correctly classified two test SUDEP patients. Discussion: This study develops a novel metric alpha, which highlights non-linear interactions between two rhythms in the ECG, and is predictive of SUDEP risk.

Electroencephalography Findings in Wrong Way Eyes: Unilateral Hemispheric Dysfunction Supporting Smooth Pursuit Asymmetry Hypothesis.

BACKGROUND: Conjugate horizontal eye deviation away from the side of the lesion, termed Wrong Way Eyes (WWE), is a rare manifestation of supratentorial lesions. The proposed etiologic hypotheses include seizure activity, compression of contralateral horizontal gaze pathways from mass effect or midline shift, and asymmetry of hemispheric smooth pursuit mechanisms. We present neurophysiological evidence that favors the asymmetry of hemispheric smooth pursuit hypothesis. METHODS: Electroencephalography (EEG) was performed in 2 patients with large left hemispheric supratentorial lesions, capturing fluctuating periods of (a) unresponsiveness with WWE and (b) relative alertness without WWE. One patient had 5 days of continuous EEG, and the other routine EEG. RESULTS: Neither patient had seizures. EEG showed normal right hemispheric activity during both unresponsiveness with WWE and alertness without WWE states. By contrast, more severe left hemispheric dysfunction was evident in the WWE state compared with the non-WWE state in both patients. In one patient, during the relatively alert state, right-beating nystagmus was observed, and drift of the eyes away from the side of the lesion was reliably seen to occur on eyelid closure and after ipsiversive volitional saccades. CONCLUSIONS: Seizure activity does not account for WWE. Compression of contralateral horizontal gaze pathways is also unlikely to account for WWE as that hypothetical mechanism should produce EEG abnormalities over the nonlesioned hemisphere, which were not seen. The findings suggest instead that a single dysfunctional hemisphere is sufficient to produce WWE. The repeated rightward drift of the eyes and nystagmus seen in one patient during relative alertness, and the observation of unilateral hemispheric dysfunction on EEG during unresponsiveness with WWE in both patients supports the idea that an imbalance of smooth pursuit mechanisms is most likely to account for this rare phenomenon.

Beamforming Seizures from the Temporal Lobe Using Magnetoencephalography.

BACKGROUND: Surgical treatment of drug-resistant temporal lobe epilepsy (TLE) depends on proper identification of the seizure onset zone (SOZ) and differentiation of mesial, temporolimbic seizure onsets from temporal neocortical seizure onsets. Noninvasive source imaging using electroencephalography (EEG) and magnetoencephalography (MEG) can provide accurate information on interictal spike localization; however, EEG and MEG have low sensitivity for epileptiform activity restricted to deep temporolimbic structures. Moreover, in mesial temporal lobe epilepsy (MTLE), interictal spikes frequently arise in neocortical foci distant from the SOZ, rendering interictal spike localization potentially misleading for presurgical planning. METHODS: In this study, we used two different beamformer techniques applied to the MEG signal of ictal events acquired during EEG-MEG recordings in six patients with TLE (three neocortical, three MTLE) in whom the ictal source localization results could be compared to ground truth SOZ localizations determined from intracranial EEG and/or clinical, neuroimaging, and postsurgical outcome evidence. RESULTS: Beamformer analysis proved to be highly accurate in all cases and was able to identify focal SOZs in mesial, temporolimbic structures. In three patients, interictal spikes were absent, too complex for dipole modeling, or localized to anterolateral temporal neocortex distant to a mesial temporal SOZ, and thus unhelpful in presurgical investigation. CONCLUSIONS: MEG beamformer source reconstruction is suitable for analysis of ictal events in TLE and can complement or supersede the traditional analysis of interictal spikes. The method outlined is applicable to any type of epileptiform event, expanding the information value of MEG and broadening its utility for presurgical recording in epilepsy.

Ovarian resection in anti-N-methyl-D-aspartate receptor encephalitis: A comparison of surgical approaches.

Background: For patients with anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) and ovarian teratoma, "conservative" surgical approaches (complete or partial unilateral oophorectomy or bilateral partial oophorectomies) are associated with clinical improvement. "Aggressive" ovarian resections (complete bilateral oophorectomy or "blind" ovarian resections without pre-operative evidence of teratoma) are also reported, although the evidence supporting these approaches is unclear. Objective: To compare the one-year functional outcomes of patients with NMDARE who underwent conservative vs. aggressive ovarian resections. Methods: Patients with NMDARE undergoing ovarian resection between January 1st, 2012 and December 31st, 2021 were retrospectively identified from three North American tertiary care centers. Primary outcome was a modified Rankin Scale score of 0-2 one year after ovarian resection. Fisher exact and Wilcoxon rank sum tests were used to compare demographic features, disease characteristics, and functional outcomes between the two surgical groups. A fixed-effects meta-analysis of studies reporting functional outcomes based on surgical approach was also performed. Results: Twenty-three patients were included. Eight underwent aggressive surgical management. There was a non-significant trend toward an association between aggressive surgical management and younger age-at-onset, higher baseline disease severity, and longer delays to treatment. There was no difference between "aggressive" (3/8, 38%) and "conservative" (11/15, 73%) management groups in achieving the primary outcome (OR95% = <0.1-1.9; p = 0.18). Findings were similar when considering data from 52 patients in two published studies (RR = 0.74; CI95% = 0.48-1.13; p = 0.16). Conclusions: Aggressive ovarian resection was not associated with improved outcomes in patients with NMDARE in this series. Group differences may have contributed, recognizing that patients who underwent aggressive resection tended to be sicker, with procedures performed later in the disease course. Based on available evidence, we advocate for function-sparing resection in patients with imaging-confirmed/suspected teratoma, and repeated multi-modal imaging in at-risk patients with NMDARE refractory to conventional treatment.