Erica Leah Von Stein

All Publications

• Pearls & Oy-sters: Exquisite Response of Sleep-Related Hypermotor Epilepsy to a Nicotine Patch. Neurology Nam, S., Von Stein, E. L., Meador, K. J., Levy, R. J., Gallentine, W., Li, Y. 2024; 103 (7): e209790

  Abstract

  Sleep-related hypermotor epilepsy (SHE), previously known as nocturnal frontal lobe epilepsy, is characterized by brief (<2 minutes) seizures with abrupt onset and offset and stereotyped focal or generalized hypermotor events occurring predominantly (but not exclusively) from sleep. Clinically, SHE can be challenging to distinguish from psychogenic nonepileptic events or sleep disorders. Up to 30% of SHE cases are drug-resistant, and SHE represents about 10% of drug-resistant surgical epilepsy cases. Although most cases have an unknown etiology, there is a subset of individuals with pathogenic variants in the subunits of n-acetylcholine receptors (nAChR). Furthermore, some individuals with nAChR variants are responsive to nicotine. We report a case of a 23-year-old man with SHE, but no pathogenic variant on testing, whose seizures were exquisitely responsive to removal and application of a nicotine patch. This suggests an alternative mechanism of nicotine in the suppression of seizures in individuals with SHE.

  View details for DOI 10.1212/WNL.0000000000209790

  View details for PubMedID 39250747

• Classifying High-Frequency Oscillations by Morphologic Contrast to Background, With Surgical Outcome Correlates. Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society Qing, K., Von Stein, E., Yamada, L., Fogarty, A., Nuyujukian, P. 2024

  Abstract

  Ictal high-frequency oscillations (HFOs) are a reliable indicator of a seizure onset zone for intracranial EEG recordings. Interictal HFOs often are also observed and may be a useful biomarker to supplement ictal data, but distinguishing pathologic from physiologic HFOs continues to be a challenging task. We present a method of classifying HFOs based on morphologic contrast to the background.We retrospectively screened 31 consecutive patients who underwent intracranial recordings for epilepsy at Stanford Medical Center during a 2-year period, and 13 patients met the criteria for inclusion. Interictal EEG data were analyzed using an automated event detector followed by morphologic feature extraction and k-means clustering. Instead of only using event features, the algorithm also incorporated features of the background adjacent to the events. High-frequency oscillations with higher morphologic contrast to the background were labeled as pathologic, and "hotspots" with the most active pathologic HFOs were identified and compared with clinically determined seizure onset zones.Clustering with contrast features produced groups with better separation and more consistent boundaries. Eleven of the 13 patients proceeded to surgery, and patients whose hotspots matched seizure onset zones had better outcomes, with 4 out of 5 "match" patients having no disabling seizures at 1+ year postoperatively (Engel I or International League Against Epilepsy Class 1-2), while all "mismatch" patients continued to have disabling seizures (Fisher exact test P-value = 0.015).High-frequency oscillations with higher contrast to background more likely represent paroxysmal bursts of pathologic activity. Patients with HFO hotspots outside of identified seizure onset zones may not respond as well to surgery.

  View details for DOI 10.1097/WNP.0000000000001121

  View details for PubMedID 39354667

• Semiautomated Detection of Early Infarct Signs on Noncontrast CT Improves Interrater Agreement. Stroke Christensen, S., Demeestere, J., Verhaaren, B. F., Heit, J. J., Von Stein, E. L., Madill, E. S., Kennedy Loube, D., Dugue, R., Rengarajan, S., Mlynash, M., Albers, G. W., Lemmens, R., Lansberg, M. G. 2023

  Abstract

  BACKGROUND: Acute ischemic infarct identification on noncontrast computed tomography (NCCT) is highly variable between raters. A semiautomated method for segmentation of acute ischemic lesions on NCCT may improve interrater reliability.METHODS: Patients with successful endovascular reperfusion from the DEFUSE 3 trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) were included. We created relative NCCT (rNCCT) color-gradient overlays by comparing the density of a voxel on NCCT to the homologous region in the contralateral hemisphere. Regions with a relative hypodensity of at least 5% were visualized. We coregistered baseline and follow-up images. Two neuroradiologists and 6 nonradiologists segmented the acute ischemic lesion on the baseline scans with 2 methods: (1) manually outlining hypodense regions on the NCCT (unassisted segmentation) and (2) manually excluding areas deemed outside of the ischemic lesion on the rNCCT color map (rNCCT-assisted segmentation). Voxelwise interrater agreement was quantified using the Dice similarity coefficient and volumetric agreement between raters with the detection index (DI), defined as the true positive volume minus the false positive volume.RESULTS: From a total of 92, we included 61 patients. Median age was 59 (64-77), and 57% were female. Stroke onset was known in 39%. Onset to NCCT was median, 8.5 hours (7-11) and median 10 hours (8.4-11.5) in patients with known and unknown onset, respectively. Compared with unassisted NCCT segmentation, rNCCT-assisted segmentation increased the Dice similarity coefficient by >50% for neuroradiologists (Dice similarity coefficient, 0.38 versus 0.83; P<0.001) and nonradiologists (Dice similarity coefficient, 0.14 versus 0.84; P<0.001), and improved the DI among nonradiologists (mean improvement, 5.8 mL [95% CI, 3.1-8.5] mL, P<0.001) but not among neuroradiologists.CONCLUSIONS: The high variability of manual segmentations of the acute ischemic lesion on NCCT is greatly reduced using semiautomated rNCCT. The rNCCT map may therefore aid acute infarct detection and provide more reliable infarct estimates for clinicians with less experience.

  View details for DOI 10.1161/STROKEAHA.123.044058

  View details for PubMedID 37909206

• Transcranial Direct Current Stimulation for Focal Status Epilepticus or Lateralized Periodic Discharges in Four Patients in a Critical Care Setting. Epilepsia Fisher, R. S., McGinn, R. J., Von Stein, E. L., Wu, T. Q., Qing, K. Y., Fogarty, A., Razavi, B., Venkatasubramanian, C. 2023

  Abstract

  OBJECTIVE: Transcranial direct current stimulation (tDCS) has been advocated for various neurological conditions, including epilepsy. A 1-4 mA cathodal current applied to the scalp over a seizure focus can reduce spikes and seizures. This series of four patients with focal status epilepticus is among the first case series to demonstrate benefit of tDCS in the critical care setting.METHODS: Patients in the intensive care unit were referred for tDCS treatment when focal status or clinically-relevant lateralized periodic discharges did not resolve with conventional anti-seizure medications and anesthetics. Battery-powered direct cathodal current at 2 mA was delivered by an ActivaDose (Caputron) tDCS device via a saline soaked sponge on the scalp over the seizure focus. Anode was on the contralateral forehead or shoulder. Treatment was for 30 minutes, repeated twice in a day, then again 1-4 times more over the next few days.RESULTS: Three females and one male, ages 34-68 were treated. Etiologies of status were PRES in association with immunosuppressants for a liver transplant, perinatal hypoxic-ischemic injury, a prior cardioembolic parietal stroke and CNS lupus. tDCS led to significant reduction of interictal spikes (0.78/s to 0.38/s, p<0.0001) in 3 cases and electrographic seizures (3.83/hr to 0/hr, p<0.001) in two cases. Medication reductions were enabled in all cases subsequent to tDCS. The only side effect of tDCS was transient erythema under the sponge in one case. Two patients died of causes unrelated to tDCS, one was discharged to a nursing home and one became fully responsive as seizures were controlled with tDCS.SIGNIFICANCE: Spikes and electrographic seizure frequency significantly improved within a day of tDCS. Results are potentially confounded by multiple ongoing changes in medications and treatments. These results might encourage further investigation of tDCS in the critical care setting, but verification by controlled studies will be required.

  View details for DOI 10.1111/epi.17514

  View details for PubMedID 36661376

• Precision medicine in epilepsy. Progress in molecular biology and translational science McGinn, R. J., Von Stein, E. L., Summers Stromberg, J. E., Li, Y. 2022; 190 (1): 147-188

  Abstract

  Epilepsy is a common neurological disorder affecting over 50 million people worldwide. Although more than 20 new anti-seizure medications have been developed in the past three decades, about one-third of patients still experience recurrent seizures. The heterogeneity of epilepsy types and the highly variable inter-individual response to the therapies makes disease management challenging. A precision medicine approach of treatment for epilepsy patients that considers individual patient characteristics has long been advocated. With advances in DNA sequencing technology, it has been estimated than >30% of all epilepsy syndromes have genetic components. Here we summarize recent approaches in genetic testing and current personalized treatments that are already applicable in genetic epilepsy syndromes. We also discuss current precision therapy utilized in personalized pharmacogenomics, as well as tailored treatment with neuromodulation for epilepsy patients. In the near future, we envision precision medicine in epilepsy will be applicable on a large scale involving not only targeted therapies, but also diagnosis, prognosis, and comorbidity management.

  View details for DOI 10.1016/bs.pmbts.2022.04.001

  View details for PubMedID 36007998

• Cryptogenic new-onset refractory status epilepticus (NORSE) following blood transfusion in a patient with severe anemia. Epileptic disorders : international epilepsy journal with videotape Wu, C. K., Culbertson, C. J., Von Stein, E. L., Walia, S., Krishnamohan, P., Threlkeld, Z. D. 2021

  Abstract

  New-onset refractory status epilepticus (NORSE) is a rare neurological emergency in which a patient without prior seizure disorder develops seemingly unprovoked status epilepticus refractory to treatment. We report the case of a middle-aged woman who developed NORSE after receiving multiple blood transfusions for subacute blood loss anemia secondary to menorrhagia. Although the mechanism is unclear, we propose that sudden changes in blood viscosity and vasogenic tone resulted in cortical edema and irritation. Although seizures have been documented in patients who undergo blood transfusion and develop posterior reversible encephalopathy syndrome (PRES), there was no radiographic evidence of PRES in this case. This is the first reported case of cryptogenic NORSE following blood transfusion.

  View details for DOI 10.1684/epd.2021.1267

  View details for PubMedID 33881399

• Cryptogenic new-onset refractory status epilepticus (NORSE) following blood transfusion in a patient with severe anemia Wu, C., Von Stein, E., Culbertson, C., Walia, S., Krishnamohan, P., Threlkeld, Z. LIPPINCOTT WILLIAMS & WILKINS. 2020

  View details for Web of Science ID 000536058006056