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“Subclinical” generalized epileptiform discharges in patients with generalized epilepsy may be associated with transitory cognitive impairment upon appropriate testing.1-4 Increased reaction time is the most sensitive behavioral correlate to these discharges.3,4

Purpose Continuous EEG can potentially be used as real-time brain telemetry for the early detection of neurologic decline. Scant literature on EEG changes related to elevated intracranial pressure (ICP) limits its use in this context. Methods Retrospective, observational case series of patients in whom we noted EEG changes correlating with a clinical concern for elevated ICP, measured or unmeasured. Results We noted EEG changes of varying severity and duration correlating with either measured or unmeasured clinical concern for elevated ICP. In two patients with recurrent transient unresponsiveness (presumed from plateau waves), generalized rhythmic delta activity and attenuation of fast activity occurred 30 minutes before a clinical change. Elevated ICP in two patients, one related to progressive mass effect from infarctions, and the other to dialysis, correlated with generalized slowing and attenuation of fast activity up to 24 hours before clinical deterioration, leading to diffuse suppression. Two patients with intraventricular hemorrhage had cyclic patterns at ∼1 per minute and ∼6 per minute (similar frequency to described frequency of Lundberg B and C waves, respectively). Conclusions Cyclic patterns and varying degrees of slowing and attenuation often preceded clinical deterioration associated with intracranial hypertension. Future systematic studies of EEG changes in this setting will facilitate early and noninvasive detection of elevated ICP.

Background High efficacy disease modifying therapies (DMT) in the management of Multiple Sclerosis (MS) have a favorable effect on relapse rate and disability progression; however, they can expose patients to significant risks, such as progressive multifocal leukoencephalopathy (PML). Objective The study aims to investigate prognostic factors that can determine outcome in MS-related PML patients. Methods We conducted a literature review and meta-analysis of 194 patients from 62 articles in PubMed, SCOPUS and EMBASE. Results Out of 194 patients (66.5% women, 33.5% men), 81% had progression in their EDSS score by at least 1 point from the time of PML diagnosis (EDSS-P group). The remaining patients had either stable or improved EDSS (EDSS-S group). In univariate analysis, older age at the time of PML diagnosis was associated with higher probability of disability accumulation and worsening of EDSS by at least 1 point (mean age = 44.8, p = 0.046). After adjusting for other variables, age at time of PML diagnosis remained a significant predictive variable in the multivariable logistic model (OR = 0.93, 95% CI: 0.88–0.99, p = 0.037). Natalizumab is the most commonly associated DMT linked to PML, followed by fingolimod and others including dimethyl fumarate, ocrelizumab, alemtuzumab. Among the different treatments used, no therapeutic agent was found to be superior in improving post-PML EDSS. Conclusions Younger age and lower JCV viral load at the time of PML diagnosis were associated with better outcome in MS-associate PML, while none of the PML therapies was superior over the others or associated with favorable outcome.

PURPOSE: Studies examining seizures (Szs) and epileptiform abnormalities (EAs) using continuous EEG in acute ischemic stroke (AIS) are limited. Therefore, we aimed to describe the prevalence of Sz and EA in AIS, its impact on anti-Sz drug management, and association with discharge outcomes. METHODS: The study included 132 patients with AIS who underwent continuous EEG monitoring >6 hours. Continuous EEG was reviewed for background, Sz and EA (lateralized periodic discharges [LPD], generalized periodic discharges, lateralized rhythmic delta activity, and sporadic epileptiform discharges). Relevant clinical, demographic, and imaging factors were abstracted to identify risk factors for Sz and EA. Outcomes included all-cause mortality, functional outcome at discharge (good outcome as modified Rankin scale of 0–2 and poor outcome as modified Rankin scale of 3–6) and changes to anti-Sz drugs (escalation or de-escalation). RESULTS: The frequency of Sz was 7.6%, and EA was 37.9%. Patients with Sz or EA were more likely to have cortical involvement (84.6% vs. 67.5% P = 0.028). Among the EAs, the presence of LPD was associated with an increased risk of Sz (25.9% in LPD vs. 2.9% without LPD, P = 0.001). Overall, 21.2% patients had anti-Sz drug changes because of continuous EEG findings, 16.7% escalation and 4.5% de-escalation. The presence of EA or Sz was not associated with in-hospital mortality or discharge functional outcomes. CONCLUSIONS: Despite the high incidence of EA, the rate of Sz in AIS is relatively lower and is associated with the presence of LPDs. These continuous EEG findings resulted in anti-Sz drug changes in one-fifth of the cohort. Epileptiform abnormality and Sz did not affect mortality or discharge functional outcomes.

Background: To study the nature and frequency of occurrence of “significant” neurological complications in coronavirus disease-2019 (COVID-19) via a systematic review of the literature.Methods: We screened all articles resulting from a search of PubMed, Cochrane, Google Scholar and Scopus, using the keywords "COVID-19 and CNS", "SARS-CoV-2 and CNS”, “COVID-19 and neurological manifestation”, “SARS2 and neurological manifestation” and “COVID-19 and Brain” looking for reports of significant neurological manifestations that would potentially have an impact on the outcome.Results: Twenty-six articles met the inclusion criteria. The significant neurological diagnoses reported were stroke, Guillain Barre Syndrome (GBS) and its variants, encephalitis, seizures, acute hemorrhagic necrotizing encephalopathy, acute disseminated encephalomyelitis (ADEM) and transverse myelitis. Although stroke, predominantly ischemic, was observed in ~ 6% of COVID-19 patients from Wuhan, China, mortality in this cohort was 38%. Of the 24 pooled patients with reports of etiology, 17 had large vessel occlusions. GBS occurred in 5/1200 (0.4%) of the COVID-19 cohort from Italy. One of the six reported encephalitis cases, the ADEM case and the report of transverse myelitis do not have data for conclusive diagnosis.Conclusion: The most frequent significant neurological association with COVID-19 is stroke, predominantly ischemic. In a cohort from Wuhan, China, this was as frequent as ~ 6%, with a 38% mortality. Most common reported etiology is large vessel occlusion. Other reported significant neurological complications are GBS/variants, encephalitis, seizures and acute hemorrhagic necrotizing encephalopathy. The reports of ADEM and transverse myelitis lacked diagnostically conclusive data.

Objectives To compare electrographic seizures, hyperexcitable patterns, and clinical outcomes in lobar and deep intraparenchymal hemorrhage. Additionally, to characterize electrographic seizure and hyperexcitable pattern predictors in each group and determine seizure risk with thalamic involvement. Design Retrospective cohort study. Setting Tertiary academic medical center. Patients Consecutive adult patients with nontraumatic intraparenchymal hemorrhage undergoing continuous electroencephalography at our center between January 2013 and December 2016. Interventions Not applicable. Measurements and main results Based on head CT closest to the initial continuous electroencephalography session, we classified intraparenchymal hemorrhage as isolated deep (no insular, subarachnoid, subdural extension) or lobar. Hyperexcitable patterns included the following: periodic discharges, spike-wave complexes, any rhythmic delta other than generalized. We used Fisher exact test for categorical and Mann-Whitney U test for continuous variables. Multivariable regression identified predictors of electrographic seizures, hyperexcitable patterns, and poor outcomes (score of 1-2 on Glasgow Outcome Scale) in lobar intraparenchymal hemorrhage. The cohort comprised of 128 patients, 88 lobar, and 40 deep intraparenchymal hemorrhage. Electrographic seizures occurred in 17% of lobar and 5% of deep intraparenchymal hemorrhage (p = 0.09). Hyperexcitable patterns were more frequent in the lobar group (44.3% vs 17.5%; p = 0.005). In multivariable analyses in the lobar group, lateralized rhythmic delta activity predicted electrographic seizures (odds ratio, 6.24; CI, 1.49-26.08; p = 0.012); insular involvement predicted hyperexcitable patterns (odds ratio, 4.88; CI, 1.36-17.57; p = 0.015); coma, temporal lobe involvement, intraparenchymal hemorrhage volume, and electrographic seizures predicted poor outcome. Thalamic involvement did not affect electrographic seizures or hyperexcitable patterns in either group. Conclusions Electrographic seizures are frequent in lobar intraparenchymal hemorrhage, occurring in one in six monitored patients, as opposed to only 5% in isolated deep intraparenchymal hemorrhage not extending to cortex/insula, subarachnoid, or subdural spaces. Patients with lobar intraparenchymal hemorrhage and lateralized rhythmic delta activity were six times as likely to have electrographic seizures, which were associated with 5.47 higher odds of a poor outcome. Coma, temporal lobe involvement, hematoma volume, and electrographic seizures predicted poor outcome in lobar intraparenchymal hemorrhage.

Objective Primary intraventricular hemorrhage (pIVH) uncommonly presents with seizures. There are no prior data regarding the frequency of seizures, periodic and rhythmic patterns on continuous electroencephalography (EEG), (cEEG) in these patients. Methods We retrospectively assessed frequency of seizures, periodic discharges, and rhythmic patterns in pIVH patients undergoing cEEG monitoring. We reviewed indications for cEEG, demographics, GCS at presentation and during cEEG, modified Graeb score (mGS), presence of hydrocephalus, cEEG duration, findings and use of antiseizure medications (ASM). cEEG patterns were classified according to location and morphology. All patterns were considered “hyperexcitable” except GRDA. The ictal‐interictal continuum (IIC) was defined as LRDA, PDs, and/or SW >1 Hz but

Unilateral ptosis may be seen in focal seizures and should be actively sought for during video-EEG (scalp and intracranial) evaluations. Further studies are needed to confirm its lateralizing value, but it was contralateral to seizure onset in this case.

A 71-year-old woman with hypertension, diabetes, and recent stroke presented with acute left hemiparesis, which started 3.5 hours earlier but improved by the time of emergency department evaluation. Examination showed mild left-sided pronator drift and sensory extinction. Her history was significant for resection of a right frontoparietal meningioma for which she had received adjuvant radiation therapy 3 years previously.

Introduction: While seizures are uncommon but reported in primary intraventricular hemorrhage (IVH), little evidence is available on the prevalence of hyperexcitable patterns on long term EEG monitoring. Methods: We sought to determine the prevalence of hyperexcitable patterns and seizures in patients with primary IVH who were extracted from a cohort consisting of patients with spontaneous intracerebral hemorrhage (sICH) who underwent continuous electroencephalogram (cEEG) monitoring between January 2013 and December 2016 at Yale-New Haven Hospital. Indications for cEEG monitoring included fluctuation of or depressed mental status, abnormal movements and a limited clinical exam. We recorded demographics, radiologic hydrocephalus, duration of EEG recording and EEG findings. Hyperexcitable patterns comprised generalized, bilateral independent or lateralized periodic discharges (PDs), lateralized rhythmic delta activity (RDA), brief potentially ictal rhythmic discharges (B(I)RDs), and spike-and-wave discharges (SW). Results: Of 196 adults with sICH who had cEEG performed, 13 patients (54% female) had primary IVH. Hydrocephalus was present in 9 patients (69%). Patients were monitored for a mean duration of 22.4 (± 14.7) hours. 9 patients had hyperexcitable patterns and/or electrographic seizures (70%): Electrographic seizures and co-existent hyperexcitable patterns were captured in 2 of 13 patients (16%) and hyperexcitable patterns without seizures in 7 of 13 patients (54%). Hyperexcitable patterns included periodic discharges (PDs) (4) (generalized, lateralized and bilateral independent, with and without rhythmicity), rhythmic delta activity (RDA) (5) (both lateralized and generalized, with and without sharps), brief potentially ictal rhythmic discharges(B(I)RDs) (1) and spike-and-wave discharges (SW) (1). There was no significant difference between patients with and without hydrocephalus and hyperexcitability or electrographic seizures (p= 0.76). Conclusion: Both electrographic seizures and/or patterns of hyperexcitability on EEG are common in our cohort of primary IVH patients. The exclusion or detection of non-convulsive seizures offers an opportunity for therapeutic intervention.

Introduction The incidence of electrographic seizures after non-traumatic intraparenchymal hemorrhage (IPH) ranges from 1.7% to 31%. It is unclear if the risk of seizures or hyperexcitable patterns (HEPs: any rhythmic delta activity except generalized, any periodic discharges, or any spike-wave pattern, using ACNS criteria) for deep IPH is similar to lobar, subarachnoid and subdural hemorrhages. We hypothesized that the incidence of seizures or hyperexcitable patterns (SZ or HEPs) in deep IPH is lower than reported, but thalamic involvement may confer higher risk due to its role in physiologic and pathologic rhythmic activity, such as sleep spindles and generalized spike wave discharges. Methods On retrospective review, 45 patients had deep IPH (defined as IPH not involving cortex/juxtacortical regions other than the insula (analyzed separately), with or without intraventricular hemorrhage IVH) and underwent continuous EEG (cEEG) between 1/2013 and 12/2016. Patients with involvement of cortex, subarachnoid or subdural areas were excluded. Age, sex, prior history of epilepsy, clinical seizure at ictus, anti-seizure drugs (ASDs), sedative infusions during EEG and surgical interventions such as ventriculostomy (EVD) or decompressive hemicraniectomy (DHC) were reviewed. The cEEG closest to admission was reviewed for seizures, HEPs, and generalized rhythmic delta activity (GRDA). The head CT in closest proximity to the index cEEG was reviewed for hematoma volume, thalamic involvement and insular involvement. Results Two of 45 patients had SZ, 7/45 had HEPs, 1/45 had both and a total of 8/45 had SZ or HEPs. Of the HEPs , LRDA was seen in 4/8, LPDs in 2/8, both LPDs and LRDA in 1/8. Of those with the lateralized HEPs, 4/7 were contralateral to IPH, 1/7 (14.2%) were bilateral and 2/7 were ipsilateral. Of the 5/7 with HEPs contralateral to the IPH, 2 had an EVD ipsilateral to the HEPs. Patients with SZ or HEPs had significantly higher hematoma volume compared to patients who did not have SZ or HEPs (32.7 ± 19.4 vs 15.4 ± 17.7, p = 0.02). Patients who underwent surgery (DHC/EVD or both) had higher incidence of HEPs or SZ compared to those who did not (7/23, 30.4% vs 1/22, 4.5%, p = 0.047). DHC was associated with significantly higher risk of SZ or HEPs (4/4, 100% vs 4/41, 9.8%, p Conclusion Risk of SZ or HEPs with deep IPH ± IVH was 17.7% and correlated with mean hematoma volume and DHC. The, risk in the absence of a surgical intervention was low (1/22, 4.5%, vs 7/23, 30.4% p = 0.047). Thalamic involvement did not correlate with SZ or HEPs in this small cohort of patients with deep IPH.

We report a case of a 32-year-old woman with a 2-year history of multiple sclerosis (MS) who presented to the ophthalmology clinic 1 week after the completion of pulse steroids with complaints of blurred vision associated with pain in the left eye. She was treated with 3 courses of high-dose methylprednisolone (1,000 mg a day for 3 days) for recurrent relapses in the 5 months before presentation (brain MRI, figure, A). Her symptoms during these relapses were left hemiparesis, right hemiparesis, and worsening right hemiparesis, in that order. She was started on glatiramer acetate 1 month before presentation. Given the frequent relapses, changing her disease-modifying therapy to natalizumab was being considered.

A 38-year-old woman presented with a right-sided throbbing headache associated with visual symptoms, nausea, vomiting, photophobia, and phonophobia. She had experienced migraines since her teenage years characterized by monthly unilateral headache associated with nausea and photophobia. The current headache had started with symptoms she recognized as her regular monthly migraine, but it had uncharacteristically persisted for 3 days. She also described a persistent aura of “pixelated 3-dimensional objects” and “colored pinwheels,” which she had not experienced with her previous headaches. Two days into the headache, she had developed a defect in her left visual field and had narrowly missed hitting a tree on that side while driving. At the time of presentation to us, she had already undergone a head CT, which was reported normal, and she was prescribed prednisone, sumatriptan, and oxycodone for management of status migrainosus, without benefit.

Introduction Refractory status epilepticus (RSE) is associated with a high mortality and morbidity. Due to ketamine’s desirable hemodynamic profile, its use in RSE has been noted to minimize the use of vasopressors. For other uses however, ketamine has been associated with hypotension, specifically in patients with depleted catecholamine stores evidenced by an elevated shock index. We report a case of myocardial depression with the use of ketamine for RSE. Methods A 64 year old, 65 kg man with a medical history significant for “weak heart” (presumed HFpEF given home medication list which only included carvedilol), chronic kidney disease, remote left middle cerebral artery stroke and resultant focal epilepsy, maintained on renally dosed levetiracetam was brought to the ER after three seizures. He received midazolam and levetiracetam 15 mg/kg, which transiently improved his mentation. He continued to have recurrent focal clonic seizures with impaired consciousness (8–11 seizures/hour lasting 2–3 min each). He was loaded with two doses of valproate 30 mg/kg followed by 40 mg/kg and levetiracetam 15 mg/kg. He also received carbamazepine 400 mg, clobazam 40 mg once and fosphenytoin 20 mg/kg phenytoin equivalent. He was subsequently intubated and midazolam infusion was initiated. Patient developed hypotension requiring norepinephrine infusion. Shock index prior to initiation of vasopressors ranged between 0.45–0.63 on a beta-blocker. Due to lack of sustained response to aforementioned anti-seizure drugs, ketamine was started (1.5 mg/kg bolus followed by an infusion uptitrated to 2 mg/kg/h), which resulted in resolution of status epilepticus but coincided with the need for escalating doses of norepinephrine and the addition of vasopressin. Midazolam infusion was discontinued. Echocardiogram (ECHO) on day 4 showed an ejection fraction (EF) of 38% with apical hypokinesis. Troponin T was elevated at 0.11 ng/ml with a BNP of 7050 pg/ml (up from 762 pg/ml a month prior). Results Ketamine was weaned off on hospital day 7 with improvement of his BP and discontinuation of vasopressors (within hours of ketamine discontinuation). Troponins normalized by day 7 (but in the setting of dialysis). Repeat ECHO on day 14 showed improved EF of 50–55% with persistent apical hypokinesis. Patient was discharged near his baseline to an acute rehabilitation facility on phenytoin and levetiracetam. Conclusion This case suggests that ketamine can be associated with cardiodepression as opposed to another cause (ie Takotsubo’s cardiomyopathy), given the temporal association of worsening and improving hemodynamics and cardiac function with the initiation and discontinuation of ketamine, respectively. Further studies are needed to understand the potential hemodynamic effect of ketamine in refractory status epilepticus, particularly in patients with underlying CHF who are often on beta blockers.

A 40-year-old woman with complex partial seizures and right hippocampal atrophy (figure, A and B) had persistent seizures after epilepsy surgery. One of her seizures is shown in the video on the Neurology ® Web site at [Neurology.org][1]. She pushes the event button during the aura (rising epigastric sensation), rubs her mouth, reaches for water, and holds onto it through the seizure. Acknowledgment: The authors acknowledge the help of Ms. Sheila Jackson in obtaining the video and the EEG from the system. [1]: http://neurology.org/lookup/doi/10.1212/WNL.0000000000002662

Sheikh et al.1 described a typical migraine persisting for 3 days and resolving after antiepileptic treatment as hemicrania epileptica (HE). EEG recording showed focal status epilepticus and transient brain MRI abnormalities attributed to ongoing seizure. This condition is rare and the proposed criteria for HE bring about the temporal relationship between onset and cessation of migraine with ictal EEG discharges. While migraine and occipital seizures are sometimes difficult to differentiate solely on …

Background: To assess the impact of new therapeutic strategies on outcomes and hospitalization charges among adult patients with botulism in the United States. Methods: We determined in-hospital outcomes and charges for patients with botulism hospitalized in 1993–1994 and compared them with those observed among patients hospitalized in 2006–2007. Mortality, length of stay, and hospitalization charges were calculated. Age, sex, race, ethnicity, and discharge status were also reported. Results: There were 66 and 132 admissions of adult patients with botulism in 1993–1994 and 2006–2007, respectively. Men predominance was observed in 2006–2007 compared to women predominance during the 1993–1994 time period. There was no significant difference in the average length of stay and in-hospital mortality rate between the two groups studied. However, in the 2006–2007 group, there was a significant increase in the mean hospitalization charges (USD 126,092 ± 120,535 vs. USD 83,623 ± 82,084; p = 0.0107) and in the proportion of patients requiring mechanical ventilation when compared to 1993–1994 (34 vs. 13.6%; p < 0.0001). Conclusion: Botulism continues to be an infrequent cause of hospitalization, with a significant increase in the average hospitalization charges in 2006–2007 when compared to 1993–1994, despite a nonsignificant change in the mortality rate and average length of hospitalization.

Objective: To determine the rate and characteristics of the occurrence of ataxia after administration of vaccination in the United States. Background Vaccination has proven to be one of the most effective methods for reducing the incidence of infectious diseases worldwide. However, there have been isolated case reports of cerebellar ataxia occurring after vaccination. Design/Methods: We used data from the Vaccine Adverse Event Reporting System (VAERS) which is a cooperative program for vaccine safety of the Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA). VAERS is a post-marketing safety surveillance program, collecting information about adverse events (possible side effects) that occur after administration of United States licensed vaccines. Results: There were 146 cases (mean age 10.4 years, range 0.5 to 61 years) of ataxia reported after vaccination in the United States from 1990 to 2010. The onset of Ataxia was within 6 weeks after vaccination in 105 cases (71.9%), and within 2 weeks in 74(50.6%), when the date of vaccination is known. Hospitalization and disability were reported in, respectively, 98 (67.1%) and 27 (18.5%) cases. Ataxia was reported in 47 (32.1%) cases after MMR vaccination, 40 (27.3%) after varicella vaccination, 33(22.6%) after Hepatitis B vaccination, 14 (0.09%) after DTAP (Diphtheria, Tetanus Toxoid, and acellular Pertussis) vaccination, and 12 (0.08%) after Hepatitis A vaccination. Conclusions: The report of most cases of ataxia within the first 6 weeks after vaccination (when the date of vaccination is known), reveals an unbalanced distribution of occurrence in this time period, with most cases reported in the first two weeks. This may suggest that some cases of ataxia are triggered by vaccination and warrants continuous and careful analysis of such cases after vaccination. Disclosure: Dr. Shekh has nothing to disclose. Dr. Abukwaik has nothing to disclose. Dr. Souayah has received personal compensation for activities with Walgreens as a consultant. Dr. Souayah has received research support from Talecris.

Objective: To analyze and compare the impact of intravenous immunoglobulin (IVIG) on outcome and cost of hospitalization of elderly patients with Myasthenia Gravis (MG) from 1992 to 2009. Background IVIG have been used to treat MG. Design/Methods: We determined the rates of occurrence, in-hospital outcomes, and mean hospital charges for elderly patients hospitalized with MG treated with IVIG between 1992 and 2009 using Nationwide Inpatient Survey (NIS). Results: The number of patients treated with IVIG varied from 3 in1997 to 63 in 2009. The average patients age varies from a minimum of 69.75 ± 6.94 in 1994 to a maximum of 78.28 ± 8.37 in 2006, p = 0.0146. Female predominance varied from 16.17 % in 1992 to 75 % in 2000, p = 0.007. The average length of hospitalization (in days) per year was not significantly different during the study time period p = 0.059. (maximum 9.8 ± 7.36 on 1993 and minimum 3 ± 0.816 on 1994). There was a significant increase in mean hospital charges per year and per patient during the study time period p Conclusions: There is a trend toward a more extensive use of IVIG to treat MG in elderly patients that paralleled a trend toward a significant increase of hospitalization charges. Disclosure: Dr. Hasan has received personal compensation for activities with Walgreens as employee. Dr. Khan has nothing to disclose. Dr. Shekh has nothing to disclose. Dr. Souayah has received personal compensation for activities with Walgreens as a consultant. Dr. Souayah has received research support from Talecris.

Objective: To assess the impact of new therapeutic strategies on outcome and cost of hospitalization among elderly patients with status epilepticus who are non mechanically ventilated in United States. Background New treatments have been introduced in the last two decades for status epilepticus in elderly patients that are expected to improve the associated in-hospital outcomes. Design/Methods: We determined the rates of occurrence, in-hospital outcomes and mean hospital charges for elderly patients hospitalized with status epilepticus from 1994 to 2009 using Nationwide Inpatient Survey (NIS). Results: The number of admission varies between in 2428 in 2004 and 4032 in 1994. The proportion of man from one year to another was significantly different during the study time period p Conclusions: A significant increase in average hospitalization charges of elderly status epilepticus non mechanically and was paralleled by trend toward the reduction of in hospital death without significant variation of average length of hospitalization. Disclosure: Dr. Patel has nothing to disclose. Dr. Kahn has nothing to disclose. Dr. Shekh has nothing to disclose. Dr. Souayah has received personal compensation for activities with Walgreens as a consultant. Dr. Souayah has received research support from Talecris.