Clinical Case Reports and Series

lyas, Adeel, Sumida, Ai, Pichardo-Rojas, Pavel S., Snyder, Kathryn M., Cho, Rhea, Bhattacharjee, Meenakshi B. Slater, Jeremy D. Kalamangalam, Giridhar P. Von Allmen, Gretchen K., Thompson, Stephen A., Lhatoo, Samden D., Johnson, Jessica A., Tandon, Nitin

Journal of Clinical Neurophysiology

42(7):p 583-591, November 2025

DOI: 10.1097/WNP.0000000000001210

Summary

Orbitofrontal epilepsies (OFE) produce variable clinical semiologies and nonspecific electrographic patterns thereby being challenging to localize. Furthermore, systematic studies of the surgical management and outcomes in OFE are sparse. The authors review the current literature and discuss the intracranial electroencephalography, microsurgical techniques, and surgical outcomes of patients in the context of a 20-year surgical experience in treating 24 patients with OFE. The authors distinguish between purely orbitofrontal resections (OF-focal, n = 10) and those in whom additional brain regions were concurrently resected (OF-plus, n = 14). These two cohorts were similar with respect to age, duration of epilepsy, and presence of an OF lesion on MRI. Patients frequently reported no auras (OF-focal: 7 [70%], OF-plus: 8 [57%]); generalized tonic–clonic seizures were common (OF-focal: 6 [60%], OF-plus: 7 [50%]); and seizures were often nocturnal (OF-focal: 5 [50%], OF-plus: 8 [57%]). Surgical extensions among the OF-plus group included the prefrontal or frontal pole (67%), temporal pole (11%), and mesial temporal lobe (22%). Durable Engel I to II outcomes at last follow-up (median: 4 years, interquartile range [IQR]: 2–7) were achieved in 5 patients (50%) with OF-focal epilepsies and 8 (57%) patients with OF-plus epilepsies. Among nonlesional cases, 4 of 11 patients (36%) achieved seizure freedom, of whom 3 (75%) underwent OF-plus resection. The most common etiology was malformation of cortical development (58%). Surgical resection of the OFE carries the same seizure-free rates as other neocortical epilepsies and can be done safely with minimal cognitive or functional decline.

Subeikshanan Venkatesan, John Whalen, Giridhar Kalamangalam,
World Neurosurgery
Volume 197
2025
123949
ISSN 1878-8750
https://doi.org/10.1016/j.wneu.2025.123949.
(https://www.sciencedirect.com/science/article/pii/S1878875025003055)

Abstract

An 18-year-old left-handed African American male presented with a year-long history of seizures characterized by episodic palpitations, sweating, and agitation. Brain magnetic resonance imaging revealed an enhancing tumor in the right anterior entorhinal cortex with adjacent amygdalar enlargement. Interictal magnetoencephalography and video-electroencephalogram -confirmed lesional right temporal lobe epilepsy. The patient underwent a partial right anterior temporal lobectomy, with histopathology revealing WHO Grade 2 pleomorphic xanthoastrocytoma with a BRAF V600 E mutation. The amygdala showed no tumor infiltration, confirming reactive hyperplasia rather than neoplastic involvement. This case underscores the importance of distinguishing tumor infiltration from benign seizure-related amygdalar enlargement in long-term epilepsy-associated tumors, usefully informing surgical strategy.

John Whalen, Subeikshanan Venkatesan, Christine Smith, Yue Wang

Neurology
Volume 104
2025
Pages 5542
10.1212/WNL.0000000000212428 [doi]
https://www.neurology.org/doi/full/10.1212/WNL.0000000000212428

Abstract

Objective: To understand the relationship between skull base dehiscence and epilepsy.

Background: Encephaloceles are known contributors to epilepsy and are primarily documented in case reports and retrospective reviews of epilepsy cohorts. While these studies highlight the prevalence of encephaloceles in epilepsy, they provide limited insight into the risk of developing epilepsy in individuals with these defects. Our study seeks to address that gap.

Design/Methods: Retrospective chart review of patients age 18 or older with diagnosis of CSF leak or encephalocele with surgical repair or found on radiological study at our center between 1/1/2010 and 12/31/2021. Exclusion criteria included inadequate documentation of radiological findings, post-traumatic or iatrogenic cause of skull defect or CSF leak, or spinal CSF leak. Among these patients, individuals with history of epilepsy were identified, excluding those with a history of childhood epilepsy.

Results: 137 patients with encephaloceles were identified. Of these, 17 developed epilepsy (12.4%). All 17 patients were female. Ten (59%) identified as African American. Sixteen (94%) had a BMI of 30 or greater. The most common location of meningoencephalocele was in the middle cranial fossa (12 patients, 70%); followed by cribiform (3, 18%); both middle cranial fossa and cribiform (1, 6%); and in tegmen tympani and cribiform (1, 6%). Regarding laterality of meningoencephalocele, 7 were left-sided, 7 were right-sided, and 3 were bilateral. All patients except one also have radiological findings consistent with idiopathic intracranial hypertension (IIH).

Conclusions: Meningoencephalocele-associated epilepsy has a moderate prevalence among all patients with skull base defects in our cohort. Among those with epilepsy and meningoencephalocele, female gender and elevated BMI are common. The location of meningoencephaloceles and radiological findings of increased intracranial pressure may differ between those who develop epilepsy and those who do not, warranting further study.

Subeikshanan Venkatesan, Abbas Babajani-Feremi, Kajal Patel, Steven N Roper, Giridhar Kalamangalam
Seizure: European Journal of Epilepsy,
Volume 126
2025
Pages 58-63
ISSN 1059-1311
https://doi.org/10.1016/j.seizure.2025.02.006.
(https://www.sciencedirect.com/science/article/pii/S1059131125000378)

Abstract

Objective: Amygdalar volumes are right-left asymmetric in normal humans. Asymmetric amygdalar hyperplasia is described in temporal lobe epilepsy (TLE), but has unclear lateralizing significance. In this study of TLE patients undergoing stereo-electroencephalography (SEEG) we examined the lateralizing value of amygdalar volume (AV) asymmetry, and its relationship to amygdalar involvement in seizures.

Methods: Amygdalar volumes of 30 TLE patients without radiological hippocampal sclerosis undergoing SEEG were compared to those from a normative database. Devising a novel amygdalar (volume) asymmetry index (AAI), we correlated AAI to SEEG-ascertained TLE lateralization and amygdalar involvement in seizures.
Results: At the group level, right AVs in right TLE (RTLE) and left AVs in left TLE (LTLE) were significantly higher than in controls (right difference: mean 226 mm3; left difference: mean 206 mm3). AAI was significantly higher than in RTLE and bitemporal epilepsy than in controls (16/17 patients; mean AAI difference 8.4 %) and significantly lower than in LTLE than in controls (8/9 patients; mean AAI difference -8.3 %). Amygdalar involvement in seizures correlated positively with absolute AAI (Spearman’s ρ = 0.45, p < 0.05).

Conclusions: Significant deviation from physiological right-left AV asymmetry is almost universal in TLE and has robust lateralizing value. Relatively positive AAI is associated with RTLE or bitemporal epilepsy; relatively negative AAI is associated with LTLE. Larger AAI deviations are associated with a higher proportion of seizures with amygdalar involvement, suggesting a causal influence of seizures on amygdalar expansion in TLE.

McCormack RM, Chandran AS, Lhatoo SD, Pati S, Li Z, Harris K, Lacuey N, Kalamangalam G, Thompson S, Tandon N.

Ann Neurol.

2024 Dec;96(6):1174-1184.

doi: 10.1002/ana.27059. Epub 2024 Sep 19. PMID: 39297387.

Abstract

Objective: Periventricular nodular heterotopia (PVNH) is the most common neuronal heterotopia, frequently resulting in pharmaco-resistant epilepsy. Here, we characterize variables that predict good epilepsy outcomes following surgical intervention using stereo-electroencephalography (SEEG) -informed magnetic resonance-guided laser interstitial thermal therapy (MRgLITT).

Methods: A retrospective review of consecutive cases from a single high-volume epilepsy referral center identified patients who underwent SEEG evaluation for PVNH to characterize the intervention and outcomes.

Results: Thirty-nine patients underwent SEEG-guided MRgLITT of the seizure onset zone (SoZ) in PVNH and associated epileptic tissue. PVNH and polymicrogyria (PMG) were densely sampled with a mean of 16.5 (SD = 2)/209.4 (SD = 36.9) SEEG probes/recording contacts per patient. Ablation principally targeted just the PVNH and cortex that was abnormal on imaging was ablated (5 patients) only if implicated in the SoZ. Volumetric analyses revealed a high percentage of PVNH SoZ ablation (96.6%, SD = 5.3%) in unilateral and bilateral (92.9%, SD = 7.2%) cases. Mean follow-up duration was 31.4 months (SD = 20.9). Seizure freedom (ILAE 1) was excellent: unilateral PVNH without other imaging abnormalities, 80%; PVNH with mesial temporal sclerosis (MTS) or PMG, 63%; bilateral PVNH, 50%. SoZ ablation percentage significantly impacted surgical outcomes (p < 0.001).

Interpretation: PVNH plays a central role in seizure genesis as revealed by dense recordings and selective targeting by LITT. MRgLITT represents a transformative technological advance in PVNH-associated epilepsy with seizure control outcomes consistent with those seen in focal lesional epilepsies. In localized unilateral cases and otherwise normal imaging, PVNH ablation without invasive recordings may be considered, and this approach deserves to be explored further.

Christine N. Smith, Stephan Eisenschenk, Yue Wang
Epilepsy & Behavior Reports
Volume 28
2024
100709
ISSN 2589-9864
https://doi.org/10.1016/j.ebr.2024.100709.
(https://www.sciencedirect.com/science/article/pii/S2589986424000662)

Abstract

Tiagabine has been associated with reports of status epilepticus as well as encephalopathy, even when used within therapeutic doses. Vagus nerve stimulation (VNS) has been used successfully to reduce seizure frequency in the outpatient setting as well as in the acute setting of status epilepticus. It is also theorized to reduce cortical synchronization. We present a case of a patient on adjunctive tiagabine therapy who developed sudden onset encephalopathy and rhythmic delta activity soon after vagus nerve stimulation was turned off in preparation for magnetic resonance imaging. The bilateral rhythmic delta activity significantly reduced in burden after VNS was turned back on, and encephalopathy also gradually improved to baseline. We hypothesize that vagus nerve stimulation successfully interrupted diffuse hypersynchrony, in the form of bilateral rhythmic delta activity, caused by tiagabine. To our knowledge, this is the first report of such a phenomenon.

Astner-Rohracher A, Ho A, Archer J, Bartolomei F, Brazdil M, Cacic Hribljan M, Castellano J, Dolezalova I, Fabricius ME, Garcés-Sanchez M, Hammam K, Ikeda A, Ikeda K, Kahane P, Kalamangalam G, Kalss G, Khweileh M, Kobayashi K, Kwan P, Laing JA, Leitinger M, Lhatoo S, Makhalova J, McGonigal A, Mindruta I, Mizera MM, Neal A, Oane I, Parikh P, Perucca P, Pizzo F, Rocamora R, Ryvlin P, San Antonio Arce V, Schuele S, Schulze-Bonhage A, Suller Marti A, Urban A, Villanueva V, Vilella Bertran L, Whatley B, Beniczky S, Trinka E, Zimmermann G, Frauscher B.

BMJ Neurol Open

2024 Aug 21

6(2):e000765. doi: 10.1136/bmjno-2024-000765. PMID: 39175939; PMCID: PMC11340713.

Abstract

Introduction: Epilepsy surgery is the only curative treatment for patients with drug-resistant focal epilepsy. Stereoelectroencephalography (SEEG) is the gold standard to delineate the seizure-onset zone (SOZ). However, up to 40% of patients are subsequently not operated as no focal non-eloquent SOZ can be identified. The 5-SENSE Score is a 5-point score to predict whether a focal SOZ is likely to be identified by SEEG. This study aims to validate the 5-SENSE Score, improve score performance by incorporating auxiliary diagnostic methods and evaluate its concordance with expert decisions.

Methods and analysis: Non-interventional, observational, multicenter, prospective study including 200 patients with drug-resistant epilepsy aged ≥15 years undergoing SEEG for identification of a focal SOZ and 200 controls at 22 epilepsy surgery centers worldwide. The primary objective is to assess the diagnostic accuracy and generalizability of the 5-SENSE in predicting focality in SEEG in a prospective cohort. Secondary objectives are to optimize score performance by incorporating auxiliary diagnostic methods and to analyze concordance of the 5-SENSE Score with the expert decisions made in the multidisciplinary team discussion.

Ethics and dissemination: Prospective multicenter validation of the 5-SENSE score may lead to its implementation into clinical practice to assist clinicians in the difficult decision of whether to proceed with implantation. This study will be conducted in accordance with the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (2014). We plan to publish the study results in a peer-reviewed full-length original article and present its findings at scientific conferences.

Lorena Figueredo Rivas, Leonid Gozman, Michael Siegel, Steven Carter, Lindsey, Le, Maria Bruzzone
Neurology
2024
2024-04-09 102(7_supplement_1): 5659
AID – 10.1212/WNL.0000000000205969 [doi]
4100 – https://www.neurology.org/doi/full/10.1212/WNL.0000000000205969

Abstract

Objective: To explore the relationship between racial disparities and post-hospitalization follow-up in patients discharged on antiseizure medications (ASM) after continuous electroencephalography (cEEG).

Background: The growing availability of in-patient EEG has led to increased diagnosis and treatment of acute symptomatic seizures (ASyS) and hyperexcitable EEG patterns. Prior studies indicate 50–90% of patients with ASyS or rhythmic and periodic patterns (RPPs), discharged on ASM, stay on them for 12–32 months. This often occurs without a clear need, promoting polypharmacy. Outpatient (OP) neurology evaluation is advised to determine the need for continuous ASM treatment.

Design/Methods: Retrospective review of patients admitted to UF hospital between January 2020 and December 2022, without prior epilepsy, who required in-patient cEEG monitoring for over 24 hours. We investigated ASM prescription patterns at discharge and at OP follow-up with neurology, neurosurgery or neuro-oncology, within 1 year post hospitalization.

Results: The cohort had 51 adult patients (25 females, 26 males). Eleven were Black, 39 were White, and 1 was identified as “Other.” While 67% were discharged on ASM and 24% were still refilling this medication at least a year later, only 44% of individuals had neurology follow-up within 6 months. Among those with follow-up, 83% were white and 13% blacks. In the group discharged with ASM, 63% of white patients had a follow-up at 1 year, as opposed to 38% of black patients. Only 1 patient in this group had seizure recurrence within 6 months.

Conclusions: Our research indicates a prevailing tendency for physicians to prescribe ASM post-discharge, irrespective of assured posthospitalization follow-up. This study highlights notable discrepancies in OP clinic attendance, with Whites having more consistent follow-ups than Blacks. Because of the risks of polypharmacy and unnecessary use of ASM, it is crucial to understand the factors limiting healthcare accessibility in vulnerable populations.

Subeikshanan Venkatesan, Giridhar Kalamangalam

Neurology

2024

5360

10.1212/WNL.0000000000205762 [doi]
https://www.neurology.org/doi/full/10.1212/WNL.0000000000205762

Abstract

Objective:(i) To discover correlations between AE/AA and amygdalar epileptiform activity (ii) To examine the predictive value of AE/AA vis-à-vis SEEG-identified TLE lateralization.

Background: Amygdalar enlargement and/or asymmetry (AE/AA) in TLE is commonly reported as occurring ipsilaterally to the seizure focus. However, AE has also been described contralaterally to the seizure focus. Small SEEG case series report amygdalar epileptiform activity in all patients but have found no lateralization value. Significance of AE/AA in the pathogenesis of TLE and its clinical utility remain unclear.

Design/Methods: We reviewed 20 pharmacoresistant TLE patients undergoing SEEG (12F) with one (14) or both (6) amygdalae sampled. We computed an amygdalar asymmetry index (AAI) from Freesurfer extracted segmentations of pre-operative structural MRIs, formulated as 200*(R_vol−L_vol)/(R_vol+L_vol). Normative amygdalar volumetric data were obtained from the ENIGMA consortium, representing lifespan data of 18000+ healthy controls.

Results: Both right and left amygdalar volumes of patients were significantly larger than controls (right mean difference (SE): 262 (302) (p< 0.001), left mean difference (SE): 114 (296) (p< 0.05)). AAI in patients (−19.5% to 31.4%; mean 12%, SD 11.1) was significantly different from controls (3.1–5.3%; mean 3.9%, SD 0.68) (p < 0.002). The overall accuracy of AAI in lateralizing TLE was 73%. Of 164 seizures captured, 78% involved the amygdala (at onset or later). Amygdalar involvement in seizure and AAI were significantly correlated (Spearman’s rho = 0.506, p = 0.023).

Conclusions: TLE may have a nonspecific enlarging effect on amygdalae, an effect accentuated for the right amygdala. Left amygdalar enlargement is highly specific but not sensitive for left TLE and right amygdalar enlargement is highly sensitive but not specific for right TLE. High correlation between amygdalar involvement in seizures and AAI may indicate an active, two-way process between amygdalar hyperplasia and seizures involving the amygdala.

Cindy Rivas, Aniela Edwards, Hannah G Rains, Maria Bruzzone, Fred S Sarfo, Alexis Simpkins

Stroke

2024

https:/www.ahajournals.org/doi/full/10/1161/str.55.suppl_1.HUP16

Abstract

Introduction: Recent reports demonstrate that stroke prevalence is expanding in young women, especially in diverse populations. Our goal was to compare the stroke type and stroke risk factors among patients with African Ancestral lineage, including African Americans (AA), West African (WA) descent from Ghana, a country in West Africa, and those without African Ancestral (WAA) lineage.

Methods: Women aged 18- 45 from our institutional stroke databases and the Kumasi, Ghana Stroke Survivors Registry between January 2014 and November 2019 were included in this retrospective study. Non-parametric t-test and chi-square analysis was used for statistical analysis to identify significant differences between stroke type and stroke risk factors.

Results: Among the 236 subjects, the median age was similar between groups (p-value 0.3940) [40 (IQR 35-43) Ghana, n= 91; 43 (IQR 34-43) in AA, n= 43, and 39 (IQR 31-43) WAA, n= 102). In the total population, 25% had an intracerebral hemorrhage, 56% had an ischemic stroke, and 19% had a subarachnoid hemorrhage. The proportion of patients with ischemic stroke was similar between groups (p-value 0.20). However, the frequency of subarachnoid hemorrhages was the lowest in the WA cohort (9%) in comparison to AA (33%) and those WAA lineage (22%), p-value 0.017. The incidence of intracerebral hemorrhage was lowest in those WAA lineage (15%) versus the AA cohort (33%) and the WA cohort (34%) p-value 0.0358. Prevalence of hypertension was highest in Ghanaians (87%) vs 60% AA, and 34% in those WAA lineage, p-value 0.0008. Patients from Ghana were less likely to smoke (1%) versus AA cohort (36%), and those WAA (31%) lineage, p-value 0.0001.

Conclusion: Significant differences were found between stroke type and risk factors in young women with stroke (hypertension, DM, and smoking), race, and country of origin. These findings are important because behavioral interventions reducing smoking and controlling blood pressure are effective for the prevention of subarachnoid and intracerebral hemorrhage. Studying social and environmental influential factors between groups may identify points of intervention to reduce stroke in AA and West African young women.

Kajal H Patel, Sotiris Mitropanopoulos, Giridhar Kalamangalam

Pearls & Oysters:  Mesial Temporal Seizures in the Absence of the Mesial Temporal Lobe

Neurology

2024

Summary

Seizure semiology represents the clinical expression of the activation of the several brain regions comprising an epileptic network. In mesial temporal lobe epilepsy (MTLE), this network includes the insular-opercular-neocortical temporal-hippocampal (IONTH) regions. In this study, we present the case of a patient with pharmacoresistant seizures characterized by nausea, lip-smacking, semi purposeful hand movements, and speechlessness, suggesting dominant hemisphere MTLE, with scalp video-EEG findings and left hippocampal sclerosis on brain MRI confirming the diagnosis. She underwent anterior temporal lobectomy with amygdalohippocampectomy and was seizure-free for 14 years before relapsing. Recurrent seizure semiology was similar to preoperative seizures, that is, consistent with left MTLE, despite the medial temporal lobe missing. Seizures were therefore assumed to arise from remnant portions of the IONTH network-the insula, operculum, and posterolateral temporal neocortex. Reinvestigation including MEG localization of spikes and acute MRI changes following a seizure cluster suggested a left opercular region epilepsy. Our patient thus demonstrated the principle that seizures with mesial temporal characteristics may arise from outside the mesial temporal lobe (MTL). MTLE semiology arises from the activation of a set of structures (the seizure network) associated with the MTL, which can be triggered by foci both within and outside the MTL itself, and indeed even in its absence. However, it is not necessary to resect the entire extended network to bring about extended periods of seizure freedom in patients with refractory MTLE.

Journal of Neurology, Neurosurgery & Psychiatry 2023;94:245-249.

https://doi.org/10.1136/jnnp-2D2022-329542

Abstract

Background: Post-traumatic epilepsy (PTE) is a severe complication of traumatic brain injury (TBI). Electroencephalography aids early post-traumatic seizure diagnosis, but its optimal utility for PTE prediction remains unknown. We aim to evaluate the contribution of quantitative electroencephalograms to predict first-year PTE (PTE₁).

Methods: We performed a multicentre, retrospective case–control study of patients with TBI. 63 PTE₁ patients were matched with 63 non-PTE₁ patients by admission Glasgow Coma Scale score, age and sex. We evaluated the association of quantitative electroencephalography features with PTE₁ using logistic regressions and examined their predictive value relative to TBI mechanism and CT abnormalities.

Results: In the matched cohort (n=126), greater epileptiform burden, suppression burden and beta variability were associated with 4.6 times higher PTE₁ risk based on multivariable logistic regression analysis (area under the receiver operating characteristic curve, AUC (95% CI) 0.69 (0.60 to 0.78)). Among 116 (92%) patients with available CT reports, adding quantitative electroencephalography features to a combined mechanism and CT model improved performance (AUC (95% CI), 0.71 (0.61 to 0.80) vs 0.61 (0.51 to 0.72)).

Conclusions: Epileptiform and spectral characteristics enhance covariates identified on TBI admission and CT abnormalities in PTE₁ prediction. Future trials should incorporate quantitative electroencephalography features to validate this enhancement of PTE risk stratification models.

Hsin-Pin Lin, Reordan O. DeJesus, Maria José Bruzzone
April 18, 2023, 100 (16_supplement_1) S146-S147
https://doi.org/10.1212/WNL.0000000000206983

Summary

A 56-year-old woman presented with electroclinical focal seizures in the setting of hyperglycemia (808 mg/dL) and elevated HbA1c of 14.7%. She had varying seizure semiology, consisting of early forced head turn to the left, speech arrest, left facial twitching, and impaired awareness. Her seizures arose from the right frontotemporal area on EEG. MRI showed hypointensities in the right prefrontal lobe that resolved after 6 months.

Venugopalan V, Casaus D, Kainz L, Slaton, C, Hurst, N, Bruzzone, M et. al.

Pharmacotherapy. 2023; 43: 6-14. doi:10.1002/phar.2744

Abstract

Study Objectives: Data evaluating cefepime thresholds associated with neurotoxicity remain limited. The objectives of this study were to evaluate the incidence of cefepime-related neurotoxicity (CRN) in patients with plasma cefepime concentrations, assess the relationship between cefepime exposure and CRN, investigate clinical factors associated with CRN, and describe electroencephalogram (EEG) abnormalities in CRN.

Design: This was a retrospective study of adult inpatients admitted between 2016 and 2018 who received cefepime therapeutic drug monitoring (TDM). Potential CRN cases were identified utilizing a standard definition. The primary outcomes of the study were to determine the incidence of CRN and evaluate the relationship between cefepime trough concentrations, the average daily AUC, and neurotoxicity. Bayesian posteriors were generated for each patient using a cefepime pharmacokinetic (PK) model, and the mean daily area under the concentration–time curve (AUC) was calculated. Multiple regression was performed to assess the association between CRN, cefepime PK, and clinical predictors of neurotoxicity.

Main Results: Four hundred eighty-one patients with 503 hospital encounters received cefepime TDM and were included in the analysis. The incidence of CRN was 4.4% (22/503). Patients with CRN had a higher incidence of renal dysfunction, hypertension, and diabetes mellitus compared to patients without CRN (non-NT). The mean cefepime trough concentration was significantly greater in the CRN patients than in the non-NT group (61.8 ± 33.7 vs. 30 ± 27.7 mg/L, respectively, p = 0.0002). Cefepime trough concentration and renal dysfunction were independently associated with increased risk of CRN in the adjusted multiple regression model. Moderate generalized slowing of the background rhythm was the most common EEG pattern associated with CRN. Delaying cefepime TDM greater than 72 h after the initiation of cefepime was associated with a 3-fold increased risk of CRN.

Conclusion: Cefepime should be used cautiously in hospitalized patients with renal dysfunction due to the risk of neurotoxicity. Dose optimization utilizing TDM early in cefepime treatment may minimize adverse effects and improve patient safety.

Rubinos, C., Bruzzone, M.J., Blodgett, C. et al. 

Neurocritical Care 38, 41–51 (2023). https://doi.org/10.1007/s12028-022-01579-z

Abstract

Background: The objective of this study was to determine the prevalence of pyridoxine deficiency, measured by pyridoxal phosphate (PLP) levels, in patients admitted to the hospital with established (benzodiazepine-resistant) status epilepticus (SE) (eSE) and to compare to three control groups: intensive care unit (ICU) patients without SE (ICU-noSE), non-ICU inpatients without SE (non-ICU), and outpatients with or without a history of epilepsy (outpatient).

Methods: This retrospective cohort study was conducted at the University of North Carolina Hospitals and Yale New Haven Hospital. Participants included inpatients and outpatients who had serum PLP levels measured during clinical care between January 2018 and March 2021. The first PLP level obtained was categorized as normal (> 30 nmol/L), marginal (≤ 30 nmol/L), deficient (≤ 20 nmol/L), and severely deficient (≤ 5 nmol/L).

Results: A total of 293 patients were included (52 eSE, 40 ICU-noSE, 44 non-ICU, and 157 outpatient). The median age was 55 (range 19–99) years. The median PLP level of the eSE group (12 nmol/L) was lower than that of the ICU-noSE (22 nmol/L, p = 0.003), non-ICU (16 nmol/L, p = 0.05), and outpatient groups (36 nmol/L, p < 0.001). Patients with eSE had a significantly higher prevalence of marginal and deficient PLP levels (90 and 80%, respectively) than patients in each of the other three groups (ICU-noSE: 70, 50%; non-ICU: 63, 54%; outpatient: 38, 21%). This significantly higher prevalence persisted after correcting for critical illness severity and timing of PLP level collection.

Conclusions: Our study confirms previous findings indicating a high prevalence of pyridoxine deficiency (as measured by serum PLP levels) in patients with eSE, including when using a more restricted definition of pyridoxine deficiency. Prevalence is higher in patients with eSE than in patients in all three control groups (ICU-noSE, non-ICU, and outpatient). Considering the role of pyridoxine, thus PLP, in the synthesis of γ-aminobutyric acid and its easy and safe administration, prospective studies on pyridoxine supplementation in patients with eSE are needed.

Brian Coffey, Giridhar Kalamangalam, Maria Bruzzone
May 3, 2022
98 (18_supplement) 3277
https://doi.org/10.1212/WNL.98.18_supplement.3277

Abstract

Objective: To describe the propagation pathway of epileptiform discharges through the Papez circuit recorded by intracranial stereotactic electroencephalography (SEEG) in a patient with intractable temporal lobe epilepsy.

Background: The Papez circuit denotes a closed-loop pathway within the modern limbic system that is integral in memory function, emotive processes, and behavior. The circuit travels from the hippocampus through the fornix to the mamillary bodies, projecting through the mammillothalamic tract to synapse in the anterior thalamic nucleus. It continues to the cingulum via the anterior thalamic radiation, coursing around the corpus callosum and retrosplenial area to end in the entorhinal cortex within the parahippocampal gyrus. A final re-entrant projection to the hippocampus completes the circuit.

Design/Methods: Case report.

Results: A 27-year-old male with pharmacoresistant right temporal lobe epilepsy was admitted for SEEG monitoring to determine candidacy for epilepsy surgery. Depth electrodes were placed targeting the right anterior amygdala (RAM), right anterior hippocampus (RAH), right posterior hippocampus (RPH), right basal temporal region (RBT), right lingula (RLIN), right retrosplenium (RRS), right posterior cingulate (RPC), right middle cingulate (RMC), and left anterior hippocampus (LAH). Observation of interictal epileptiform discharges revealed that spike onsets seen first in RAH were closely followed by RPH and consistently seen 170–190 ms later over RRS, RPC, and RMC. The latter sequence was consistent with antidromic propagation in the Papez circuit, initiating in the hippocampal head, propagating through the fornix into the cingulate bundle, and presumably into the anterior thalamus thereafter.

Conclusions: Hippocampal evoked potentials have been observed in response to stimulation of the anterior nucleus of the thalamus in deep-brain stimulation (DBS) studies (REF – Osorio et. al.). This SEEG patient had sampling of multiple limbic structures and demonstrated the reciprocal effect of endogenous epileptiform potentials originating in the hippocampus propagating retrogradely in the Papez circuit toward the thalamus via the fornix and cingulum.

Figueredo Rivas, L., Bruzzone Giraldez, M., & Simpkins, A. N.

2021

The Neurodiagnostic Journal, 61(3), 150–156.

https://doi.org/10.1080/21646821.2021.1959217

Abstract

Ambulatory electroencephalogram (AEEG) can be a cost-effective and valuable alternative to in-patient long-term EEG monitoring. A potential benefit of AEEG is that it allows monitoring in the patient’s unique home environment. While this can be more affordable and convenient for the patient, it can also present unique challenges for the reviewer. Unlike long-term monitoring in an epilepsy unit, the AEEG recording occurs in a less controlled environment and most often without immediate EEG technical assistance during the recording. As a result, unique EEG artifacts can occur with AEEG. Their recognition and correct interpretation are crucial for proper EEG analysis. This report presents a case of a patient who underwent a 72-hour AEEG to evaluate symptoms initially concerning for subclinical seizures. During the AEEG recording, the patient had a tactile encounter with an electric fence. This tactile event resulted in a unique, not previously reported, pattern clouding an otherwise normal study. By conducting a brief review of the most common non-physiologic environmental artifacts encountered in modern EEG monitoring, we aim to emphasize the importance of patient education to prevent artifactual pollution. This knowledge can facilitate planning and help avoid environmental influences that may create artifacts when recording in an uncontrolled setting.

Marra, David E; Busl, Katharina M; Robinson, Christopher P; Bruzzone, Maria J; Miller, Amber H; Chen, Zhaoyi; Guo, Yi Lyu, Tianchen; Bian, Jiang; Smith, Glenn E

Critical Care Explorations 3(6):p e0456, June 2021. 

DOI: 10.1097/CCE.0000000000000456

Abstract

Objectives: To determine if early CNS symptoms are associated with severe coronavirus disease 2019.

Design: A retrospective, observational case series study design.

Setting: Electronic health records were reviewed for patients from five healthcare systems across the state of Florida, United States.
Patients: A clinical sample (n = 36,615) of patients with confirmed diagnosis of coronavirus disease 2019 were included. Twelve percent (n = 4,417) of the sample developed severe coronavirus disease 2019, defined as requiring critical care, mechanical ventilation, or diagnosis of acute respiratory distress syndrome, sepsis, or severe inflammatory response syndrome.

Interventions: None.

Measurement and Main Results: We reviewed the electronic health record for diagnosis of early CNS symptoms (encephalopathy, headache, ageusia, anosmia, dizziness, acute cerebrovascular disease) between 14 days before the diagnosis of coronavirus disease 2019 and 8 days after the diagnosis of coronavirus disease 2019, or before the date of severe coronavirus disease 2019 diagnosis, whichever came first. Hierarchal logistic regression models were used to examine the odds of developing severe coronavirus disease 2019 based on diagnosis of early CNS symptoms. Severe coronavirus disease 2019 patients were significantly more likely to have early CNS symptoms (32.8%) compared with nonsevere patients (6.11%; χ²[1] = 3,266.08, p < 0.0001, φ = 0.29). After adjusting for demographic variables and pertinent comorbidities, early CNS symptoms were significantly associated with severe coronavirus disease 2019 (odds ratio = 3.21). Diagnosis of encephalopathy (odds ratio = 14.38) was associated with greater odds of severe coronavirus disease 2019; whereas diagnosis of anosmia (odds ratio = 0.45), ageusia (odds ratio = 0.46), and headache (odds ratio = 0.63) were associated with reduced odds of severe coronavirus disease 2019.

Conclusions: Early CNS symptoms, and specifically encephalopathy, are differentially associated with risk of severe coronavirus disease 2019 and may serve as an early marker for differences in clinical disease course. Therapies for early coronavirus disease 2019 are scarce, and further identification of subgroups at risk may help to advance understanding of the severity trajectories and enable focused treatment.

Keith J. Kincaid, Justin C. Kung, Alexander J. Senetar, David Mendoza, Daniel A. Bonnin, Windy L. Purtlebaugh, Rainier M. Cabatbat, Rondalyn Dickens, Franklin D. Echevarria, Vidhu Kariyawasam, Maria Bruzzone, Alexis N. Simpkins
eNeurologicalSci
Volume 23 2021
100340 ISSN 2405-6502
https://doi.org/10.1016/j.ensci.2021.100340.
(https://www.sciencedirect.com/science/article/pii/S2405650221000320)

Abstract

Novel coronavirus SARS-CoV-2 has created unprecedented healthcare challenges. Neurologic deficits are often an important presenting symptom. To date, the only reported post-infectious COVID-19 manifestations of neurologic disease include cognitive deficits and dysfunction of the peripheral nervous system. Here we report that seizure can also be a post-COVID-19 or “long-COVID” complication. We present a 71-year-old man with hypertension, diabetes mellitus, and COVID-19 diagnosed by RT-PCR who initially presented with posterior circulation stroke-like symptoms, which completely resolved after emergent thrombolysis. Six days later, the patient returned with seizure activity, supported by radiographic and electroencephalographic studies. Notably, he was negative for SARS-CoV-2, and no other provoking factor was uncovered after a comprehensive work-up. To our knowledge, this is the first report of post-infectious seizures after a case of COVID-19, highlighting the potential importance of monitoring for neurologic symptoms in COVID-19 patients, even after convalescence.

Maria Jose Bruzzone Giraldez and W. Curt LaFrance Jr
Neurology
August 11, 2020
95 (6) 237-238
https://doi.org/10.1212/WNL.0000000000009861
https://orcid.org/0000-0002-4901-3852

Abstract

This editorial highlights the alarming findings from recent research showing that patients with psychogenic nonepileptic seizures (PNES) face a significantly elevated risk of premature death. Drawing on a large retrospective cohort study of over 5,500 video-EEG monitored patients, the authors underscore that individuals with PNES have a standardized mortality ratio (SMR) of 2.5 compared to the general population, a rate comparable to that of patients with drug-resistant epilepsy. Particularly concerning is the substantially higher risk in young patients (under 30), whose mortality risk was eight-fold above expected. The causes of death were varied: external causes accounted for 18% of fatalities; among patients under 50, suicide represented 20%; and in nearly a quarter of cases, “epilepsy” was listed as the cause of death. The authors argue that these data should serve as a “wake-up call” for the neurology and psychiatry communities: there is an urgent need for more timely diagnosis, better risk stratification, and effective preventative strategies to reduce avoidable deaths in PNES. They further call for rethinking long-held notions of PNES as a benign, purely “functional” disorder.

Rondalyn Dickens, Alexander Senetar, Esther Olasoji, Hannah Branstetter, Niran Vijayaraghavan, Tri M Huynh, Maria Bruzzone, Alexis N Simpkins 
Stroke
Volume 52, Number Suppl_1
https://doi.org/10.1161/str.52.suppl_1.15

Abstract

Introduction: The COVID-19 pandemic has impacted stroke care and highlighted health care disparities. We aimed to determine if stroke alert (SA) volume, stroke alert mimic (SAM) volume, utilization of reperfusion therapies, and socioeconomic and race ethnic determinants of clinical outcome were impacted by the pandemic.

Methods: Data was obtained from our Institutional Review Board approved SA database from February 2019-June 2019 and February 2020-June 2020 to capture the impact of the stay at home orders enacted at the end of March 2020 and the increase of COVID-19 cases in Florida in June 2020. Regression analysis was used to identify differences in volumes of SA, reperfusion therapy, SAM, and clinical factors (NIHSS, age, sex, race, ethnicity, insurance status, and rural region).

Results: A total of 1171 SA were included, median age 66 (interquartile range 55-76), 50% woman, 23% Black, 68% Non-Hispanic White, 1% Hispanic, 8% unknown; 52% of the SA were SAM. SA volumes, thrombolysis and endovascular therapy use was unchanged. The volume of SAM did not differ between time intervals, but SAM were more likely to be older (odds ratio (OR) 1.03, 95% confidence interval (CI) 1.02 – 1.04), White (OR 1.80, 95% CI 1.09 -2.99), uninsured (OR 2.19, 95% CI 1.35 – 3.46), arrive by EMS (OR 1.77, 95% CI 1.31- 2.40), and have a higher NIHSS (OR 1.02, 95% CI 1.003 – 1.034). SAM secondary to migraine, intoxication, medication toxicity, or psychiatric disease were less likely to occur in April 2020 (OR 0.37, CI 0.15- 0.96) and in patients from rural regions (OR 0.42, CI 0.19 – 0.95). They were more likely to occur in older patients (OR 1.06, CI 1.05-1.07) and men (OR 2.31, CI 1.62 – 3.31). SAM secondary to seizure were more likely to occur in April 2020 (OR 2.46, CI 1.06- 0.96) and Whites (OR 2.22, CI 1.16 -4.26). SAM from medical or non-cerebrovascular or epileptic neurologic disease were unchanged.

Conclusions: Significant changes in the frequency of SAM subtypes occurred in close proximity to stay-at-home orders. Our findings suggest that a proportion of Blacks and Hispanics were not accessing healthcare for stroke like symptoms during the stay-at-home orders. Thus, patient education on how to access healthcare in vulnerable populations should be included with implementation of stay at home orders.

Nitin Tandon, Brian A. Tong, Elliott R. Friedman, Jessica A. Johnson, Gretchen Von Allmen, Melissa S. Thomas, Omotola A. Hope, Giridhar P. Kalamangalam, Jeremy D. Slater, Stephen A. Thompson

JAMA Neurol. 2019;76(6):672–681.

doi:10.1001/jamaneurol.2019.0098

Abstract

Importance:  A major change has occurred in the evaluation of epilepsy with the availability of robotic stereoelectroencephalography (SEEG) for seizure localization. However, the comparative morbidity and outcomes of this minimally invasive procedure relative to traditional subdural electrode (SDE) implantation are unknown.

Objective:  To perform a comparative analysis of the relative efficacy, procedural morbidity, and epilepsy outcomes consequent to SEEG and SDE in similar patient populations and performed by a single surgeon at 1 center.

Design, Setting and Participants:  Overall, 239 patients with medically intractable epilepsy underwent 260 consecutive intracranial electroencephalographic procedures to localize their epilepsy. Procedures were performed from November 1, 2004, through June 30, 2017, and data were analyzed in June 2017 and August 2018.

Interventions:  Implantation of SDE using standard techniques vs SEEG using a stereotactic robot, followed by resection or laser ablation of the seizure focus.

Main Outcomes and Measures:  Length of surgical procedure, surgical complications, opiate use, and seizure outcomes using the Engel Epilepsy Surgery Outcome Scale.

Results:  Of the 260 cases included in the study (54.6% female; mean [SD] age at evaluation, 30.3 [13.1] years), the SEEG (n = 121) and SDE (n = 139) groups were similar in age (mean [SD], 30.1 [12.2] vs 30.6 [13.8] years), sex (47.1% vs 43.9% male), numbers of failed anticonvulsants (mean [SD], 5.7 [2.5] vs 5.6 [2.5]), and duration of epilepsy (mean [SD], 16.4 [12.0] vs17.2 [12.1] years). A much greater proportion of SDE vs SEEG cases were lesional (99 [71.2%] vs 53 [43.8%]; P < .001). Seven symptomatic hemorrhagic sequelae (1 with permanent neurological deficit) and 3 infections occurred in the SDE cohort with no clinically relevant complications in the SEEG cohort, a marked difference in complication rates (P = .003). A greater proportion of SDE cases resulted in resection or ablation compared with SEEG cases (127 [91.4%] vs 90 [74.4%]; P < .001). Favorable epilepsy outcomes (Engel class I [free of disabling seizures] or II [rare disabling seizures]) were observed in 57 of 75 SEEG cases (76.0%) and 59 of 108 SDE cases (54.6%; P = .003) amongst patients undergoing resection or ablation, at 1 year. An analysis of only nonlesional cases revealed good outcomes in 27 of 39 cases (69.2%) vs 9 of 26 cases (34.6%) at 12 months in SEEG and SDE cohorts, respectively (P = .006). When considering all patients undergoing evaluation, not just those undergoing definitive procedures, favorable outcomes (Engel class I or II) for SEEG compared with SDE were similar (57 of 121 [47.1%] vs 59 of 139 [42.4%] at 1 year; P = .45).

Conclusions and Relevance:  This direct comparison of large, matched cohorts undergoing SEEG and SDE implantation reveals distinctly better procedural morbidity favoring SEEG. These modalities intrinsically evaluate somewhat different populations, with SEEG being more versatile and applicable to a range of scenarios, including nonlesional and bilateral cases, than SDE. The significantly favorable adverse effect profile of SEEG should factor into decision making when patients with pharmacoresistant epilepsy are considered for intracranial evaluations.

Veena Venugopalan, Cara Nys, Natalie Hurst, Yiqing Chen, Maria Bruzzone, Kartikeya Cherabuddi, Nicole Iovine, Jiajun Liu, Mohammad Al Shaer, Marc Scheetz, Nathaniel Rhodes, Charles Peloquin, Kenneith Klinker

bioRxiv 2020.08.13.250456; doi: https://doi.org/10.1101/2020.08.13.250456

Abstract

Background: The incidence of cefepime-induced neurotoxicity (CIN) in hospitalized patients is highly variable. Although greater cefepime exposures incite neurotoxicity, data evaluating trough thresholds associated with CIN remains limited. The objectives of this study were to evaluate the incidence of CIN, assess the relationship between cefepime trough concentrations and CIN, investigate clinical factors associated with CIN, and describe electroencephalogram (EEG) abnormalities in CIN.

Methods: This was a retrospective study of adult patients who had received ≥ 5 days of cefepime with ≥ 1 trough concentration > 25 mg/L. Potential CIN cases were identified utilizing neurological symptoms, neurologist assessments, EEG findings and improvement of neurotoxicity after cefepime discontinuation.

Results: One-hundred and forty-two patients were included. The incidence of CIN was 13% (18/142). The mean cefepime trough concentration in CIN patients was significantly greater than the non-neurotoxicity group (74.2 mg/L ± 41.1 vs. 46.6 mg/L ± 23, p=0.015). Lower renal function (creatinine clearance < 30 ml/min), greater time to therapeutic drug monitoring (TDM) (≥72 hours), and each 1 mg/mL rise in cefepime trough were independently associated with increased risk of CIN. Moderate generalized slowing of the background rhythm was the most common EEG pattern associated with CIN.

Conclusion: Cefepime should be used cautiously in hospitalized patients due to the risk of neurotoxicity. Patients with greater renal function and those who had early cefepime TDM (≤ 72 hours) had lower risk of CIN.

Kwo Wei David Ho, Christine Smith, Miguel Chuquilin, Maria Jose Bruzzone

Journal of Clinical Neuroscience

Abstract

A 51-year-old male with a history of multiple myeloma presented with progressive lower extremity sensory impairment after receiving intrathecal methotrexate therapy. MRI revealed extensive T2 hyperintensity in the posterior column of the spinal cord, suggestive of myelopathy. Despite ruling out other common causes through comprehensive testing, methotrexate-induced myelopathy was identified as the most likely diagnosis. Treatment with vitamin supplementation showed no improvement.