Faculty Bibliography

OBJECTIVE:There is evidence for central nervous system complications of coronavirus disease 2019 (COVID-19) infection, including encephalopathy. Encephalopathy caused by or arising from seizures, especially nonconvulsive seizures (NCS), often requires electroencephalography (EEG) monitoring for diagnosis. The prevalence of seizures and other EEG abnormalities among COVID-19-infected patients is unknown. METHODS:Medical records and EEG studies of patients hospitalized with confirmed COVID-19 infections over a 2-month period at a single US academic health system (four hospitals) were reviewed to describe the distribution of EEG findings including epileptiform abnormalities (seizures, periodic discharges, or nonperiodic epileptiform discharges). Factors including demographics, remote and acute brain injury, prior history of epilepsy, preceding seizures, critical illness severity scores, and interleukin 6 (IL-6) levels were compared to EEG findings to identify predictors of epileptiform EEG abnormalities. RESULTS:Of 111 patients monitored, most were male (71%), middle-aged or older (median age 64 years), admitted to an intensive care unit (ICU; 77%), and comatose (70%). Excluding 11 patients monitored after cardiac arrest, the most frequent EEG finding was moderate generalized slowing (57%), but epileptiform findings were observed in 30% and seizures in 7% (4% with NCS). Three patients with EEG seizures did not have epilepsy or evidence of acute or remote brain injury, although all had clinical seizures prior to EEG. Only having epilepsy (odds ratio [OR] 5.4, 95% confidence interval [CI] 1.4-21) or seizure(s) prior to EEG (OR 4.8, 95% CI 1.7-13) was independently associated with epileptiform EEG findings. SIGNIFICANCE/CONCLUSIONS:Our study supports growing evidence that COVID-19 can affect the central nervous system, although seizures are unlikely a common cause of encephalopathy. Seizures and epileptiform activity on EEG occurred infrequently, and having a history of epilepsy or seizure(s) prior to EEG testing was predictive of epileptiform findings. This has important implications for triaging EEG testing in this population.

There have been multiple descriptions of seizures during the acute infectious period in patients with COVID-19. However, there have been no reports of status epilepticus after recovery from COVID-19 infection. Herein, we discuss a patient with refractory status epilepticus 6 weeks after initial infection with COVID-19. Extensive workup demonstrated elevated inflammatory markers, recurrence of a positive nasopharyngeal SARS-CoV-2 polymerase chain reaction, and hippocampal atrophy. Postinfectious inflammation may have triggered refractory status epilepticus in a manner similar to the multisystemic inflammatory syndrome observed in children after COVID-19.

The term 'implantation effect' is used to describe an immediate and transient improvement in seizure frequency following an intracranial study for seizure onset localization. We conducted a retrospective analysis of 190 consecutive patients undergoing intracranial electroencephalogram (EEG) monitoring, of whom 41 had no subsequent resection/ablation/stimulation; 33 had adequate data and follow-up time available for analysis. Analysis of seizure frequency following an intracranial study showed 36% (12/33) responder rate (>50% seizure reduction) at one year, decreasing and stabilizing at 20% from year 4 onwards. In addition, we describe three patients (9%) who had long term seizure freedom of more than five years following electrode implantation alone, two of whom had thalamic depth electrodes. Electrode implantation perhaps leads to a neuromodulatory effect sufficient enough to disrupt epileptogenic networks. Rarely, this may be significant enough to even result in long term seizure freedom, as seen in our three patients.

BACKGROUND:Little is known about the effect of the Coronavirus disease 2019 pandemic on stroke care and the impact of the epidemic on acute stroke hospitalizations has not been described. METHODS:We analyze the stroke admission rate in three hospitals in New York City from January 1, 2020 through April 17, 2020, identifying all cases of acute ischemic stroke, intraparenchymal hemorrhage and subarachnoid hemorrhage. RESULTS:We confirmed 518 cases of out-of-hospital stroke. During the baseline period up to February 25, 2020, the daily stroke admission rate was stable, with the slope of the regression describing the number of admissions over time equal to -0.33 (se = 1.21), not significantly different from 0 (p = 0.79), with daily admissions averaging 41. During the pandemic period, the slope was -4.4 (se = 1.00); i.e., the number of stroke admissions decreased an average of 4.4 per week, (p = 0.005), with weekly admissions averaging 23, a reduction of 44% versus baseline. This general result was not different by patient age, sex, or race/ethnicity. CONCLUSIONS:The weekly stroke admission rate started declining two weeks prior to the local surge of coronavirus admissions. The consequences of lack of diagnosis and treatment of a large proportion of acute stroke patients are likely severe and lasting.

Background. Mab is a MDR nontuberculous mycobacterium that causes lung infections in patients with structural lung disease. Mab harbors a chromosomally encoded class A beta-lactamase, BlaMab, able to hydrolyze penicillins, cephalosporins and carbapenems. L,D- and D,D-transpeptidases (L,D TP and D,D TP) shape peptidoglycan (PG) synthesis and contribute to cell wall structure. Select combinations of beta-lactams that inhibit L,D TP and D,D TPs and BlaMab are desirable as they can potentially improve treatment outcomes. DUR is a novel

Acute-onset and severe sensory and autonomic deficits with no motor dysfunction, typically preceded by a febrile illness, with poor recovery, and often fatal outcome are the hallmark features of acute sensory and autonomic neuronopathy (ASANN). Pathologically and electrophysiologically, ASANN is characterized by an extensive ganglionopathy affecting sensory and autonomic ganglia with preservation of motor neurons. Consequently, patients, usually children or young adult, develop acute-onset profound widespread loss of all sensory modalities resulting in automutilations, as well as autonomic failure causing neurogenic orthostatic hypotension, neurogenic underactive bladder, and gastroparesis and constipation. The diagnosis is clinical with support of nerve conduction studies and autonomic testing, as well as spinal cord magnetic resonance imaging showing characteristic posterior cord hyperintensities. Although the presumed etiology is immune-mediated, further studies are required to clarify the physiopathology of the disease. We here performed a systematic review of the epidemiology, pathophysiology, diagnosis, and management of ASANN, with three representative cases that recently presented at our clinic. All three patients had the typical clinical manifestations of ASANN but in different combinations, illustrating the variable phenotype of the disorder. Immunosuppression is seldom effective. Management options are limited to supportive and symptomatic care with the goal of minimizing complications and preventing death.

Head and neck tumors can affect afferent baroreceptor neurons and either interrupt or intermittently increase their signaling, causing blood pressure to become erratic. When the afferent fibers of the baroreflex are injured by surgery or radiotherapy or fail to develop as in familial dysautonomia, their sensory information is no longer present to regulate arterial blood pressure, resulting in afferent baroreflex failure. When the baroreflex afferents are abnormally activated, such as by paragangliomas in the neck, presumably by direct compression, they trigger acute hypotension and bradycardia and frequently syncope, by a mechanism similar to the carotid sinus syndrome. We describe our observations in a large series of 23 patients with afferent baroreflex dysfunction and the cardiovascular autonomic features that arise when the sensory baroreceptor neurons are injured or compressed. The management of afferent baroreceptor dysfunction is limited, but pharmacological strategies can mitigate blood pressure swings, improve symptoms, and may reduce hypertensive organ damage. Although rare, the prevalence of afferent baroreflex dysfunction appears to be increasing in middle-aged men due to human papillomavirus related oropharyngeal cancer.

Background: To assess acute clinical effects and safety of single-dose oral ampreloxetine, a novel, long-acting, selective norepinephrine reuptake inhibitor in subjects with neurogenic orthostatic hypotension (nOH).
Method(s): In a 5-day dosing study, subjects received placebo on Day 1, followed by ascending doses of ampreloxetine (range:1-20 mg). A subset of subjects were randomized to placebo or ampreloxetine in a 1-day double-blind study. Assessments included change in seated and standing systolic blood pressure (SBP), and Orthostatic Hypotension Symptom Assessment-Item 1 (OHSA#1; dizziness, lightheadedness, feeling faint).
Result(s): Of 34 subjects (mean age, 66 years), 15 and 13 subjects received ampreloxetine 10 and 20 mg, respectively, as maximum tolerated dose. Ampreloxetine 10 mg showed the most consistent response for increase in seated SBP relative to placebo (mean [SD] change in seated SBP 4.9 [20.1] mmHg more than placebo 4 hours post-dose). In the double-blind study (ampreloxetine, n=5 [median dose, 10 mg]; placebo, n=5), relative to placebo, for the ampreloxetine treatment group, increase in seated (mean difference from placebo, 29.9 mmHg at 4 hours post-dose; p < 0.05) and 3-minute standing SBP (mean difference, 35.0 mmHg at 4 hours post-dose) was more pronounced for the ampreloxetine treatment group to 9 hours and 10 hours post-dose, respectively, and 3-minute standing SBP was more pronounced for subjects randomized to ampreloxetine up to 10 hours post-dose. Twice as many subjects in the ampreloxetine treatment arm reported symptom improvement on OHSA#1. Most common adverse events were headache and urinary tract infection, with no serious events.
Conclusion(s): In subjects with nOH, 10 mg ampreloxetine produced a consistent increase in seated SBP relative to placebo. Compared to placebo, ampreloxetine showed greater increase in seated and standing SBP up to 10 hours post-dose, and greater symptom improvement. Ampreloxetine was well tolerated. These results support assessment of longer-term effects of ampreloxetine in nOH.
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