Objective: We sought to determine if global cognitive function in patients with epilepsy (PWE) differs when electroencephalographic (EEG) abnormalities are present during concurrent neuropsychological (NP) evaluation. Methods: We explored the association between subclinical epileptiform discharges (sEDs) and interictal epileptiform discharges (IEDs) and global aspects of cognition in 79 consecutive PWE who underwent continuous EEG monitoring during NP evaluation for diagnostic (15%) or presurgical (85%) purposes while on their standard antiseizure medication (ASM) regimens. As some researchers have suggested that the apparent link between IEDs and cognition represent epiphenomena of an underlying damaged neural substrate, we used functional status as a stratifying covariate to allow us to address this position. Results: Despite being on their standard ASM regimen, EEG was abnormal in 68% of patients. Epileptiform abnormalities (IEDs, sEDs, or both) were seen in isolation or coupled with diffuse or focal slowing in 38% of patients. Individuals with IEDs occurring during their NP evaluation demonstrated poorer scores in attention/working memory (forward and backward digit span), processing speed (symbol searching and coding), and speeded components of language (semantic fluency) tests compared with those with normal EEG tracings matched by their real-world, functional status. In two high functioning patients, performance was significantly better when these individuals were tested in the absence of IEDs, with performances appearing invalid when tested during periods of IED activity. No significant association was found between NP performance and nonepileptiform EEG abnormalities. Significance: A substantial proportion of PWE undergoing NP evaluation manifest concurrent EEG abnormalities, with epileptiform abnormalities associated with poorer global cognitive performance. As this pattern was observed regardless of functional status, this association appears to represent more than unrelated features coincidentally shared by the lowest functioning cohort. Coupled with our individual case data, our findings suggest that NP testing may be adversely affected by IEDs and sEDs going unrecognized in the absence of simultaneous EEG recordings, and set the stage for future studies to definitively establish this possible relationship.

Objective: Magnetic resonance imaging (MRI)–guided laser interstitial thermal therapy (MRg-LITT) is an alternative to open epilepsy surgery. We assess safety and effectiveness of MRg-LITT for extratemporal lobe epilepsy (ETLE) in patients who are considered less favorable for open resection. Methods: We retrospectively reviewed sequential cases of patients with focal ETLE who underwent MRg-LITT between 2012 and 2019. Epileptogenic zones were determined from standard clinical and imaging data ± stereoelectroencephalography (SEEG). Standard stereotactic techniques, MRI thermometry, and a commercial laser thermal therapy system were used for ablations. Anatomic MRI was used to calculate ablation volumes. Clinical outcomes were determined longitudinally. Results: Thirty-five patients with mean epilepsy duration of 21.3 ± 12.2 years underwent MRg-LITT for focal ETLE at a mean age 36.4 ± 12.7 years. A mean 2.59 ± 1.45 trajectories per patient were used to obtain ablation volumes of 8.8 ± 7.5 cm3. Mean follow-up was 27.3 ± 19.5 months. Of 32 patients with >12 months of follow-up, 17 (53%) achieved good outcomes (Engel class I + II) of whom 14 (44%) were Engel class I. Subgroup analysis revealed better outcomes for patients with lesional ETLE than for those who were nonlesional, multifocal, or who had failed prior interventions (P =.02). Of 13 patients showing favorable seizure-onset patterns (localized low voltage fast activity or rhythmic spiking on SEEG) prior to ablation, 9 (69%) achieved good outcomes, whereas only 3 of 11 (27%) who show other slower onset patterns achieved good outcomes. Minor adverse events included six patients with transient sensorimotor neurologic deficits and four patients with asymptomatic hemorrhages along the fiber tract. Major adverse events included one patient with a brain abscess that required stereotactic drainage and one patient with persistent hypothalamic obesity. Three deaths—two seizure-associated and one suicide—were unrelated to surgical procedures. Significance: MRI-guided laser interstitial thermal therapy (or MRg-LITT) was well-tolerated and yielded good outcomes in a heterogeneous group of ETLE patients. Lesional epilepsy and favorable seizure-onset patterns on SEEG predicted higher likelihoods of success.

The symptoms of functional neurological disorder (FND) are a product of its pathophysiology. The pathophysiology of FND is reflective of dysfunction within and across different brain circuits that, in turn, affects specific constructs. In this perspective article, we briefly review five constructs that are affected in FND: emotion processing (including salience), agency, attention, interoception, and predictive processing/inference. Examples of underlying neural circuits include salience, multimodal integration, and attention networks. The symptoms of each patient can be described as a combination of dysfunction in several of these networks and related processes. While we have gained a considerable understanding of FND, there is more work to be done, including determining how pathophysiological abnormalities arise as a consequence of etiologic biopsychosocial factors. To facilitate advances in this underserved and important area, we propose a pathophysiology-focused research agenda to engage government-sponsored funding agencies and foundations.

Temporal lobe epilepsy is associated with MRI findings reflecting underlying mesial temporal sclerosis. Identifying these MRI features is critical for the diagnosis and management of temporal lobe epilepsy. To date, this process relies on visual assessment by highly trained human experts (e.g. neuroradiologists, epileptologists). Artificial intelligence is increasingly recognized as a promising aid in the radiological evaluation of neurological diseases, yet its applications in temporal lobe epilepsy have been limited. Here, we applied a convolutional neural network to assess the classification accuracy of temporal lobe epilepsy based on structural MRI. We demonstrate that convoluted neural networks can achieve high accuracy in the identification of unilateral temporal lobe epilepsy cases even when the MRI had been originally interpreted as normal by experts. We show that accuracy can be potentiated by employing smoothed grey matter maps and a direct acyclic graphs approach. We further discuss the foundations for the development of computer-aided tools to assist with the diagnosis of epilepsy.

Purpose Exclusive right hemisphere language lateralization is rarely observed in the Wada angiography results of epilepsy surgery patients. Cortical stimulation mapping (CSM) is infrequently performed with such patients, as most undergo non-dominant left hemisphere resections, which are presumed not to pose any risk to language. Early language reorganization is typically assumed in such individuals, taking left hemisphere epileptiform activity as confirmation of change resulting from a pathological process. We present data from CSM and Wada studies demonstrating that right hemisphere language occurs in the absence of left hemisphere pathology, suggesting it can exist as a normal, but rare variant, in some individuals. Further, these data confirm the Wada test findings of atypical dominance. Methods Cortical stimulation mapping data were examined for all right hemisphere surgical patients with right hemisphere speech at our Center between 1974 and 2006. Out of 1209 interpretable Wada procedures, 89 (7.4%) patients had exclusive right hemisphere speech, and 21 (1.7%) of these patients underwent surgery involving the right hemisphere. Language site location was determined by examining intraoperative photographs, and site distribution was statistically compared to published findings from left hemisphere language dominant patients (Ojemann et al., 1989). Key Findings Language cortex was identified in the right hemisphere during CSM for all patients with available data. All sites could be classified in superior or middle temporal gyri, inferior parietal lobe, or inferior frontal gyrus; all of which were common zones where language was identified in the left hemisphere dominant comparison sample. Significance Results suggest: 1) the Wada procedure is a valid measure for identifying right hemisphere language processing without any false lateralization found in the patients mapped with CSM (i.e., a positive Wada is 100% sensitive for finding RH language sites), and 2) the distribution of language sites is consistent across right hemisphere and left hemisphere language dominant patients, supporting the theory that right hemisphere language can occur as a normal variant of language lateralization.

We present a 56 year-old, right-handed, congenitally deaf, female who exhibited a partial Balint's syndrome accompanied by positive visual phenomena restricted to her lower right visual quadrant (e.g., color band, transient unformed visual hallucinations). Balint's syndrome is characterized by a triad of visuo-ocular symptoms that typically occur following bilateral parieto-occipital lobe lesions. These symptoms include the inability to perceive simultaneous events in one's visual field (simultanagnosia), an inability to fixate and follow an object with one's eyes (optic apraxia), and an impairment of target pointing under visual guidance (optic ataxia). Our patient exhibited simultanagnosia, optic ataxia, left visual-field neglect, and impairment of all complex visual-spatial tasks, yet demonstrated normal visual acuity, intact visual-fields, and an otherwise normal neurocognitive profile. The patient's visuo-ocular symptoms were noticed while she was participating in rehabilitation for a small right pontine stroke. White matter changes involving both occipital lobes had been incidentally noted on the CT scan revealing the pontine infarction. As the patient relied upon sign language and reading ability for communication, these visuo-perceptual limitations hindered her ability to interact with others and gave the appearance of aphasia. We discuss the technical challenges of assessing a patient with significant barriers to communication (e.g., the need for a non-standardized approach, a lack of normative data for such special populations), while pointing out the substantial contributions that can be made by going beyond the standard neuropsychological test batteries.

Pathogenic variants in SPTAN1 result in abnormal neurodevelopment but limited information is available on the spectrum of neurodevelopmental profiles associated with variations in this gene. We present novel data collected at two time points over a three-year period in a nine-year-old patient with heterozygous de novo SPTAN1 variant, drug-resistant epilepsy, and left hippocampal sclerosis. Across evaluations, our patient's performance was highly variable, ranging from below age expectation to within age-expected range. The patient exhibited relative cognitive strengths at both time points on verbal-expressive tasks. Weaknesses were seen in her attention, executive function, psychomotor processing speed, fine motor, visual-motor integration, and social skills. Memory findings were consistent those associated with left hippocampal sclerosis. Evaluations resulted in diagnoses including attention deficit hyperactivity disorder and autism spectrum disorder.

Objective: To define left temporal lobe regions where surgical resection produces a persistent postoperative decline in naming visual objects. Methods: Pre- and postoperative brain magnetic resonance imaging data and picture naming (Boston Naming Test) scores were obtained prospectively from 59 people with drug-resistant left temporal lobe epilepsy. All patients had left hemisphere language dominance at baseline and underwent surgical resection or ablation in the left temporal lobe. Postoperative naming assessment occurred approximately 7 months after surgery. Surgical lesions were mapped to a standard template, and the relationship between presence or absence of a lesion and the degree of naming decline was tested at each template voxel while controlling for effects of overall lesion size. Results: Patients declined by an average of 15% in their naming score, with wide variation across individuals. Decline was significantly related to damage in a cluster of voxels in the ventral temporal lobe, located mainly in the fusiform gyrus approximately 4-6 cm posterior to the temporal tip. Extent of damage to this region explained roughly 50% of the variance in outcome. Picture naming decline was not related to hippocampal or temporal pole damage. Significance: The results provide the first statistical map relating lesion location in left temporal lobe epilepsy surgery to picture naming decline, and they support previous observations of transient naming deficits from electrical stimulation in the basal temporal cortex. The critical lesion is relatively posterior and could be avoided in many patients undergoing left temporal lobe surgery for intractable epilepsy.

BACKGROUND:: Surgery is indicated for cerebral cavernous malformations (CCMs) that cause medically refractory epilepsy. Real-time magnetic resonance thermography (MRT)-guided stereotactic laser ablation (SLA) is a minimally invasive approach to treating focal brain lesions. SLA of CCM has not previously been described. OBJECTIVE:: To describe MRT-guided SLA, a novel approach to treating CCM-related epilepsy, with respect to feasibility, safety, imaging, and seizure control in 5 consecutive patients. METHODS:: Five patients with medically refractory epilepsy undergoing standard presurgical evaluation were found to have corresponding lesions fulfilling imaging characteristics of CCM and were prospectively enrolled. Each underwent stereotactic placement of a saline-cooled cannula containing an optical fiber to deliver 980-nm diode laser energy via twist drill craniostomy. MR anatomic imaging was used to evaluate targeting before ablation. MR imaging provided evaluation of targeting and near real-time feedback regarding the extent of tissue thermocoagulation. Patients maintained seizure diaries, and remote imaging (6-21 months postablation) was obtained in all patients. RESULTS:: Imaging revealed no evidence of acute hemorrhage following fiber placement within presumed CCM. MRT during treatment and immediate postprocedure imaging confirmed the desired extent of ablation. We identified no adverse events or neurological deficits. Four of 5 (80%) patients achieved freedom from disabling seizures after SLA alone (Engel class 1 outcome), with follow-up ranging 12 to 28 months. Reimaging of all subjects (6-21 months) indicated lesion diminution with surrounding liquefactive necrosis, consistent with the surgical goal of extended lesionotomy. CONCLUSION:: Minimally invasive MRT-guided SLA of epileptogenic CCM is a potentially safe and effective alternative to open resection. Additional experience and longer follow-up are needed. ABBREVIATIONS:: CCM, cerebral cavernous malformationsGRE, gradient recalled echoMRT, magnetic resonance thermographySLA, stereotactic laser ablation

Language and theory of mind (ToM) are the cognitive capacities that allow for the successful interpretation and expression of meaning. While functional MRI investigations are able to consistently localize language and ToM to specific cortical regions, diffusion MRI investigations point to an inconsistent and sometimes overlapping set of white matter tracts associated with these two cognitive domains. To further examine the white matter tracts that may underlie these domains, we use a two-tensor tractography method to investigate the white matter microstructure of 809 participants from the Human Connectome Project. 20 association white matter tracts (10 in each hemisphere) are uniquely identified by leveraging a neuroanatomist-curated automated white matter tract atlas. The fractional anisotropy (FA), mean diffusivity (MD), and number of streamlines (NoS) are measured for each white matter tract. Performance on neuropsychological assessments of semantic memory (NIH Toolbox Picture Vocabulary Test, TPVT) and emotion perception (Penn Emotion Recognition Test, PERT) are used to measure critical subcomponents of the language and ToM networks, respectively. Regression models are constructed to examine how structural measurements of left and right white matter tracts influence performance across these two assessments. We find that semantic memory performance is influenced by the number of streamlines of the left superior longitudinal fasciculus III (SLF-III), and emotion perception performance is influenced by the number of streamlines of the right SLF-III. Additionally, we find that performance on both semantic memory & emotion perception is influenced by the FA of the left arcuate fasciculus (AF). The results point to multiple, overlapping white matter tracts that underlie the cognitive domains of language and ToM. Results are discussed in terms of hemispheric dominance and concordance with prior investigations.