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Electrically stimulated auras as a potential biomarker of the epileptogenic zone

Bank, Anna M; Billakota, Santoshi; Bateman, Lisa M; Hamberger, Marla J; Cole, Jeffrey; McKhann, Guy M; Feldstein, Neil; Schevon, Catherine A
Electrocortical stimulation mapping (ESM) is often performed in patients undergoing stereoelectroencephalography (SEEG) prior to epilepsy surgery, with the goal of identifying functional cortex and preserving it postoperatively. ESM may also evoke a patient's typical seizure semiology. The purpose of this study was to determine whether the sites at which typical auras are evoked during ESM are associated with other known clinical and electrophysiologic biomarkers of the epileptogenic zone: the seizure onset zone (SOZ), the early spread zone (ES), and high-frequency oscillations (HFOs). We found that the sites at which auras were provoked were not consistently associated with known biomarkers (p = 0.09). We conclude that evoked auras during ESM may reflect electrical spread rather than true epileptogenicity, and that a larger study is needed to assess their potential value as independent epileptic biomarkers.
PMID: 34139619
ISSN: 1525-5069
CID: 4917632

Neurologic Manifestations of Systemic Disease: Seizure [Review]

Billakota, Santoshi; Steriade, Claude; French, Jacqueline
ISSN: 1092-8480
CID: 4573512

Personalized medicine: Vinpocetine to reverse effects of GABRB3 mutation

Billakota, Santoshi; Andresen, J Michael; Gay, Bryant C; Stewart, Gregory R; Fedorov, Nikolai B; Gerlach, Aaron C; Devinsky, Orrin
OBJECTIVE:To screen a library of potential therapeutic compounds for a woman with Lennox-Gastaut syndrome due to a Y302C GABRB3 (c.905A>G) mutation. METHODS:We compared the electrophysiological properties of cells with wild-type or the pathogenic GABRB3 mutation. RESULTS:Among 1320 compounds, multiple candidates enhanced GABRB3 channel conductance in cell models. Vinpocetine, an alkaloid derived from the periwinkle plant with anti-inflammatory properties and the ability to modulate sodium and channel channels, was the lead candidate based on efficacy and safety profile. Vinpocetine was administered as a dietary supplement over 6 months, reaching a dosage of 20 mg three times per day, and resulted in a sustained, dose-dependent reduction in spike-wave discharge frequency on electroencephalograms. Improved language and behavior were reported by family, and improvements in global impression of change surveys were observed by therapists blinded to intervention. SIGNIFICANCE/CONCLUSIONS:Vinpocetine has potential efficacy in treating patients with this mutation and possibly other GABRB3 mutations or other forms of epilepsy. Additional studies on pharmacokinetics, potential drug interactions, and safety are needed.
PMID: 31755996
ISSN: 1528-1167
CID: 4209432

Why we urgently need improved epilepsy therapies for adult patients

Billakota, Santoshi; Devinsky, Orrin; Kim, Kyung-Wha
PURPOSE/OBJECTIVE:Up to a third of patients with epilepsy suffer from recurrent seizures despite therapeutic advances. RESULTS:Current epilepsy treatments are limited by experiential data from treating different types of epilepsy. For example, we lack evidence-based approaches to efficacious multi-drug therapies or identifying potentially serious or disabling adverse events before medications are initiated. Despite advances in neuroscience and genetics, our understanding of epilepsy pathogenesis and mechanisms of treatment-resistance remains limited. For most patients with epilepsy, precision medicine for improved seizure control and reduced toxicity remains a future goal. CONCLUSION/CONCLUSIONS:A third of epilepsy patients suffer from ongoing seizures and even more suffer from adverse effects of treatment. There is a critical need for more effective and safer therapies for epilepsy patients with frequent comorbitidies, including depression, anxiety, migraine, and cognitive impairments, as well as special populations (e.g., women, elderly). Advances from genomic sequencing techniques may identify new genes and regulatory elements that influence both the depth of the epilepsies' roots within brain circuitry as well as ASD resistance. Improved understanding of epilepsy mechanisms, identification of potential new therapeutic targets, and their assessment in randomized controlled trials are needed to reduce the burden of refractory epilepsy.
PMID: 31751547
ISSN: 1873-7064
CID: 4209212

Cannabinoid therapy in epilepsy

Billakota, Santoshi; Devinsky, Orrin; Marsh, Eric
PURPOSE OF REVIEW/OBJECTIVE:To review the history, pharmacology, and clinical science of cannabidiol (CBD) in the treatment of epilepsy. RECENT FINDINGS/RESULTS:Phase III randomized controlled trials and prospective open label trials have provided efficacy and safety data for the use of CBD in pediatric onset severe epilepsies. The product that was studied in the vast majority of these published trials, Epidiolex (>99% of CBD and <0.10% Δ9-tetrahydrocannabinol (THC); GW pharmaceuticals, Cambridge, UK), has now been FDA approved based on this published data. SUMMARY/CONCLUSIONS:Identification of CBD, Δ9-THC, and the endocannabinoid system in the mid-20th century has led to advancement of cannabis-based therapies for epilepsy. Based on clinical trial data, Epidiolex is the first CBD medication approved by a national regulatory agency (US Food and Drug Administration for Dravet and Lennox Gastaut syndrome; European Medicines Agency for Lennox Gastaut syndrome). Approval of CBD as a treatment for these rare and severe pediatric-onset epilepsy syndromes is an important milestone, but the complete spectrum of use of cannabis-derived products, and the use of CBD for other epilepsy syndromes remains to be determined.
PMID: 30676535
ISSN: 1473-6551
CID: 3610672

Addition of a hospital bedside sitter during intracranial stereotactic EEG monitoring improves safety and seizure responses in an adult epilepsy monitoring unit

Kamitaki, Brad K; Billakota, Santoshi; Bateman, Lisa M; Pack, Alison M
Expert consensus statements recommend continuous observation for patients undergoing intracranial electroencephalography (EEG), but this practice is neither universal nor specific regarding the type of observation. We compared outcomes for patients who underwent intracranial stereotactic EEG (SEEG) before and after the adoption of continuous monitoring by a staff bedside sitter. We retrospectively studied 26 consecutive adult patients who underwent SEEG placement at our center over a three-year period. Thirteen patients were monitored with usual protocol (no-sitter group), and 13 patients had a full-time hospital-employed sitter at bedside (sitter group). We analyzed nursing responses for all electroclinical seizures and characterized seizure-related adverse events. More seizures went unrecognized without a sitter (33.3% versus 15.0% of all seizures; p = 0.03). Two unrecognized focal to bilateral tonic-clonic seizures occurred only in the no-sitter group. Nursing response was significantly faster in the sitter group in relation to both electrographic seizure onset (12.0 s, p = 0.04) and clinical seizure onset (13.5 s, p = 0.02). Two patients in the no-sitter group pulled their electrodes out periictally while none did so in the sitter group. The addition of a full-time staff bedside sitter improved nursing response times and lowered the rate of unrecognized seizures in patients with SEEG monitoring. Sitters also helped to eliminate inadvertent major electrode displacement.
PMID: 30036764
ISSN: 1525-5069
CID: 3212372

Sleep-disordered breathing, neuroendocrine function, and clinical SUDEP risk in patients with epilepsy

Billakota, Santoshi; Odom, Nicole; Westwood, Andrew J; Hanna, Eric; Pack, Alison M; Bateman, Lisa M
INTRODUCTION/BACKGROUND:Sudden unexpected death in epilepsy (SUDEP) is a major contributor to epilepsy-related mortality. It is associated with nocturnal seizures and centrally mediated postictal cardiorespiratory dysfunction (CRD), but mechanisms and contributors remain poorly understood. METHODS:We performed a prospective, cross-sectional, observational pilot study in the Columbia University Medical Center (CUMC) adult epilepsy monitoring unit (EMU) to explore relationships between periictal CRD, sleep-disordered breathing (SDB), neuroendocrine function, and clinical SUDEP risk. Thirty patients (twenty women, ten men) underwent video-electroencephalogram (EEG) with electrocardiogram (EKG) and digital pulse oximetry, inpatient or outpatient polysomnography (PSG), and comprehensive laboratory evaluation of sex steroid hormones. Sudden unexpected death in epilepsy risk was defined as Low (0-2) or High (≥3) using the revised SUDEP-7 Inventory. Sleep-disordered breathing was defined using standard criteria. Neuroendocrine dysfunction was defined as ≥1 laboratory abnormality. RESULTS:Cardiorespiratory dysfunction occurred more frequently in high-risk patients (60% vs. 27%, p = 0.018). Endocrine dysfunction was seen in 35% of patients, more in men (p = 0.018). Sleep-disordered breathing was found in 88% of fully scoreable PSGs. CONCLUSIONS:There was no significant relationship between CRD, SDB, and neuroendocrine status, though all PSGs in those with high SUDEP risk or neuroendocrine dysfunction revealed SDB. Larger studies are needed to further elucidate relationships between CRD, SDB, neuroendocrine factors, and SUDEP.
PMID: 30176573
ISSN: 1525-5069
CID: 3271072

Laser ablation is effective for temporal lobe epilepsy with and without mesial temporal sclerosis if hippocampal seizure onsets are localized by stereoelectroencephalography

Youngerman, Brett E; Oh, Justin Y; Anbarasan, Deepti; Billakota, Santoshi; Casadei, Camilla H; Corrigan, Emily K; Banks, Garret P; Pack, Alison M; Choi, Hyunmi; Bazil, Carl W; Srinivasan, Shraddha; Bateman, Lisa M; Schevon, Catherine A; Feldstein, Neil A; Sheth, Sameer A; McKhann, Guy M
OBJECTIVE:Selective laser amygdalohippocampotomy (SLAH) using magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is emerging as a treatment option for drug-resistant mesial temporal lobe epilepsy (MTLE). SLAH is less invasive than open resection, but there are limited series reporting its safety and efficacy, particularly in patients without clear evidence of mesial temporal sclerosis (MTS). METHODS:We report seizure outcomes and complications in our first 30 patients who underwent SLAH for drug-resistant MTLE between January 2013 and December 2016. We compare patients who required stereoelectroencephalography (SEEG) to confirm mesial temporal onset with those treated based on imaging evidence of MTS. RESULTS:Twelve patients with SEEG-confirmed, non-MTS MTLE and 18 patients with MRI-confirmed MTS underwent SLAH. MTS patients were older (median age 50 vs 30 years) and had longer standing epilepsy (median 40.5 vs 5.5 years) than non-MTS patients. Engel class I seizure freedom was achieved in 7 of 12 non-MTS patients (58%, 95% confidence interval [CI] 30%-86%) and 10 of 18 MTS patients (56%, 95% CI 33%-79%), with no significant difference between groups (odds ratio [OR] 1.12, 95% CI 0.26-4.91, P = .88). Length of stay was 1 day for most patients (range 0-3 days). Procedural complications were rare and without long-term sequelae. SIGNIFICANCE/CONCLUSIONS:We report similar rates of seizure freedom following SLAH in patients with MTS and SEEG-confirmed, non-MTS MTLE. Consistent with early literature, these rates are slightly lower than typically observed with surgical resection (60%-80%). However, SLAH is less invasive than open surgery, with shorter hospital stays and recovery, and severe procedural complications are rare. SLAH may be a reasonable first-line surgical option for patients with both MTS and SEEG confirmed, non-MTS MTLE.
PMID: 29392715
ISSN: 1528-1167
CID: 2989272

The extrapolated reference values procedure: Theory, algorithm, and results in patients and control subjects

Nandedkar, Sanjeev D; Sanders, Donald B; Hobson-Webb, Lisa D; Billakota, Santoshi; Barkhaus, Paul E; Stålberg, Erik V
INTRODUCTION/BACKGROUND:Reference values (RVs) are required to separate normal from abnormal values obtained in electrodiagnostic (EDx) testing. However, it is frequently impractical to perform studies on control subjects to obtain RVs. The Extrapolated Reference Values (E-Ref) procedure extracts RVs from data obtained during clinically indicated EDx testing. We compared the E-Ref results with established RVs in several sets of EDx data. METHODS:The mathematical basis for E-Ref was explored to develop an algorithm for the E-Ref procedure. To test the validity of this algorithm, it was applied to simulated and real jitter measurements from control subjects and patients with myasthenia gravis, and to nerve conduction studies from patients with various conditions referred for EDx studies. RESULTS:There was good concordance between E-Ref and RVs for all evaluated data sets. DISCUSSION/CONCLUSIONS:E-Ref is a promising method to develop RVs. Muscle Nerve 57: 90-95, 2018.
PMID: 28181271
ISSN: 1097-4598
CID: 3197562

Ultrasound Imaging of Median Nerve Conduit in a Patient With Persistent Median Nerve Symptoms

Billakota, Santoshi; Ruch, David S; Hobson-Webb, Lisa D
Peripheral nerve injury can be reconstructed using composite polymer nerve autografts, but the sonographic appearance of nerve wraps and conduits have not been well documented. This case report describes the sonographic findings in a 42-year-old woman with bilateral carpal tunnel syndrome status post nerve repair with a conduit. The cross-sectional area of the left median nerve was 24 mm at the carpal tunnel inlet and 5 mm at the forearm. The wrist to forearm ratio was 4.8. There was a hypoechoic space surrounding the nerve that was 1.8 to 1.9 mm thick and bordered by a thin, hyperechoic outer rim. On review of the operative record and consultation with her surgeon (DR), it was determined that this represented the 2-mm nerve wrap used in the last surgery. Inclusion of these structures with the median nerve measured a total area of 52 mm at its maximum. In describing this image, we hope to lay the foundation for describing the sonographic appearance of peripheral nerve repair.
PMID: 28557906
ISSN: 1537-1603
CID: 3197572