Demonstrating new-onset or worsened sudomotor function post-COVID-19 on comparative analysis of autonomic function pre-and post-SARS-CoV-2 infection.

Background: Autonomic dysfunction including sudomotor abnormalities have been reported in association with SARS-CoV-2 infection. Objective: There are no previous studies that have compared autonomic function objectively in patients pre- and post- SARS-CoV-2 infection.We aimed to identify if SARS-CoV-2 virus is triggering and/or worsening dysautonomia by comparing autonomic function tests in a group of patients pre-and post-SARS-CoV-2 infection. Design/methods: Six participants were enrolled and divided into two groups. The first group of 4 participants reported worsened autonomic symptoms post-SARS-CoV-2 infection. These individuals had their first autonomic test prior to COVID-19 pandemic outbreak (July 2019-December 2019). Autonomic function testing was repeated in these participants, 6 months to 1-year post-SARS-CoV-2 infection (June 2021).The second group of 2 participants reported new-onset autonomic symptoms post-COVID-19 infection and were also tested within 6 months post-SARS-CoV-2 infection.All participants had mild COVID-19 infection per WHO criteria. They had no evidence of large fiber neuropathy as demonstrated by normal neurophysiological studies (EMG/NCS). They were all screened for known causes of autonomic dysfunction and without risk factors of hypertension/hyperlipidemia, thyroid dysfunction, diabetes/prediabetes, vitamin deficiencies, history of HIV, hepatitis, or syphilis, prior radiation or chemical exposure or evidence of monoclonal gammopathy, or autoimmune condition. Results: Participants were female (age: 21-37y) and all endorsed orthostatic intolerance (6/6). Gastrointestinal symptoms (⅚), new-onset paresthesias, (3/6), and sexual dysfunction (2/6) were reported. Parasympathetic autonomic function remained stable 6-months to 1-year post-COVID-19 infection and no parasympathetic dysfunction was demonstrated in participants with new-onset dysautonomia symptoms. Postural orthostatic tachycardia was noted in half of the patients, being observed in one patient pre- SARS-CoV-2 infection and persisting post-SARS-CoV-2 infection; while new-onset postural tachycardia was observed in 1/3rd of patients. Sympathetic cholinergic (sudomotor) dysfunction was demonstrated in ALL participants. Worsened, or new-onset, sudomotor dysfunction was demonstrated in those with mild or normal sudomotor function on pre-COVID-19 autonomic testing. Conclusions: Sympathetic adrenergic and cholinergic dysautonomia probably account for some of the symptoms of Long COVID-19. Sudomotor dysfunction was demonstrated as consistently worsened or new-sequelae to COVID-19 infection. COVID-19 may be responsible for triggering new-onset or worsened small-fiber neuropathy in this sample, supporting previously reported studies with similar findings. However, the findings in our study are preliminary, and studies with larger sample size are needed to confirm these observations.

Electroclinical Mismatch During EEG Acquisition: What It Might Mean, What We Might Need to Do.

An electroclinical mismatch is present if the electroencephalogram (EEG) shows evidence of moderate to severe diffuse encephalopathy but the patient's mental status is only mildly altered. We describe five cases in which seizure or status epilepticus was suspected due to electroclinical mismatch. In all five cases, EEG was ordered to rule out nonconvulsive status epilepticus as the cause of the altered mental status. EEG initially showed generalized delta activity (GDA), with variable degrees of rhythmicity, with or without superimposed theta activity, with or without sporadic epileptiform discharges. During EEG acquisition, all patients followed commands and answered questions. The mental status change was limited to mild inattention and temporal disorientation. Benzodiazepine challenge was performed by administering lorazepam 2-mg IV. Within 10 minutes of injection, GDA started to break up and subsequently disappeared. EEG showed prominent sleep spindles in three patients and background changes, indicating drowsiness in two patients. The assessment of clinical response to lorazepam was confounded by sleepiness in all patients. Serial EEG recording or continuous EEG monitoring revealed reemergence of GDA, at times appearing more rhythmic than the GDA in the baseline study. All patients received nonsedating antiseizure drugs. GDA completely resolved and mental status normalized two to five days after starting antiseizure medication. In cases of electroclinical mismatch, the absence of clear-cut epileptiform discharges does not exclude the possibility that cortical hyperexcitability is contributing to the encephalopathic process. A positive response to benzodiazepine challenge suggests the presence of cortical hyperexcitability and the need to start, or increase the dosage of, antiseizure drugs.

Hemi-parkinsonism and return of essential tremors after MRgFUS thalamotomy: Case report and review of procedural complications affecting ventral thalamic nuclei.

Magnetic resonance guided focused ultrasound (MRgFUS) thalamotomy targets the ventral intermediate nucleus of the thalamus and has been shown to be safe and effective to treat medication-resistant essential tremors. Improvement in tremor scores, posture and action scores, disability scores and quality of life scores have been reported in patients treated with this procedure. Adverse events are usually transient and non-severe. We present a patient who underwent MRgFUS thalamotomy of the left VIM and developed new-onset parkinsonian features predominantly on the right side and return of essential tremors a few years after the procedure. Changes in speech (hypophonia and dysarthria), gait imbalance and postural instability, bradykinesia, and cogwheeling rigidity occurred, likely due to involvement of the fiber tracts through the ventrolateral subnuclei and the adjacent ventral anterior thalamic nuclei and other surrounding structures. We describe side effects of MRgFUS thalamotomy in our patient compared to previous reports and review the thalamic nuclei and surrounding structures that can be affected during procedure, causing these effects.

Altered mental status predicts length of stay but not death in a community-based cohort of hospitalized COVID-19 patients.

INTRODUCTION: Altered Mental Status (AMS) is a common neurological complication in patients hospitalized with the diagnosis of COVID-19 (Umapathi et al., 2020; Liotta et al., 2020). Studies show that AMS is associated with death and prolonged hospital stay. In addition to respiratory insufficiency, COVID-19 causes multi-organ failure and multiple metabolic derangements, which can cause AMS, and the multi-system involvement could account for the prolonged hospital stay and increased mortality. In this study, we built on our previous publication (Chachkhiani et al., 2020) using a new, larger cohort to investigate whether we could reproduce our previous findings while addressing some of the prior study's limitations. Most notably, we sought to determine whether AMS still predicted prolonged hospital stay and increased mortality after controlling for systemic complications such as sepsis, liver failure, kidney failure, and electrolyte abnormalities. OBJECTIVES: The primary purpose was to document the frequency of AMS in patients with COVID-19 at the time of presentation to the emergency room. Secondary aims were to determine: 1) if AMS at presentation was associated with worse outcomes as measured by prolonged hospitalization and death; and 2) if AMS remained a predictor of worse outcome after adjusting for concomitant organ failure and metabolic derangements. RESULTS: Out of 367 patients, 95 (26%) had AMS as a main or one of the presenting symptoms. Our sample has a higher representation of African Americans (53%) than the US average and a high frequency of comorbidities, such as obesity (average BMI 29.1), hypertension (53%), and diabetes (30%). Similar to our previous report, AMS was the most frequent neurological chief complaint. At their admission, out of 95 patients with AMS, 83 (88%) had organ failure or one of the systemic problems that could have caused AMS. However, a similar proportion (86%) of patients without AMS had one or more of these same problems. Age, race, and ethnicity were the main demographic predictors. African Americans had shorter hospital stay [HR1.3(1.0,1.7),p = 0.02] than Caucasians. Hispanics also had shorter hospital stay than non-Hispanics [HR1.6(1.2,2.1), p = 0.001]. Hypoxia, liver failure, hypernatremia, and kidney failure were also predictors of prolonged hospital stay. In the multivariate model, hypoxia, liver failure, and acute kidney injury were the remaining predictors of longer hospital stay, as well as people with AMS at baseline [HR0.7(0.6,0.9), p < 0.02] after adjusting for the demographic characteristics and clinical predictors. AMS at baseline predicted death, but not after adjusting for demographics and clinical variables in the multivariate model. Hypoxia and hyperglycemia at baseline were the strongest predictors of death. CONCLUSION: Altered mental status is an independent predictor of prolonged hospital stay, but not death. Further studies are needed to evaluate the causes of AMS in patients with COVID-19.

Neurological complications of COVID19 during March 2020 at LCMC health university medical center: Dataset.

We reviewed the electronic medical records (EMR) of patients hospitalized during the peak of the pandemic, March 1st through March 31st, to document the type and frequency of neurological problems seen in patients with COVID-19 at presentation to the emergency room. Secondary aims were to determine: 1) the frequency of neurological complaints during the hospital stay; 2) whether the presence of any neurological complaint at presentation or any of the individual types of neurological complaints at admission predicted three separate outcomes: death, length of hospital stay, or the need for intubation; and 3) if the presence of any neurological complaint or any of the individual types of neurological complaints developed during hospital stay predicted the previous three outcomes. SETTING: The Louisiana Health Sciences Center - New Orleans Institutional Review Board and the University Medical Center Clinical Research Review Committee approved the study protocol. DATA ACQUISITION: We reviewed the electronic medical records (EMR) of patients hospitalized during March (March 1st through March 31st) 2020 at the University Medical Center New Orleans (UMCNO), who tested positive for SARS-CoV-2 during the same hospitalization. The EMR team generated a list of 257 patients admitted for COVID-19. We excluded seven patients because of a negative COVID-19 test result or incomplete medical record documentation. Three neurology residents (DC, MS, DB) reviewed the EMR in detail to capture the relevant medical history, clinical course, and laboratory test results and abstracted data into an electronic data collection spreadsheet.We recorded the presentation or development of the following neurological complaints: headache, syncope, altered mental status, seizure, status epilepticus, and ischemic or hemorrhagic stroke. STATISTICAL ANALYSIS: We used "R" (statistics software) and Microsoft Excel to generate summary tables. To analyze hospital length of stay or death, we fitted a competing risks proportional hazards model for time to discharge or death using the crr() function in R version 4.0.0. The competing risks model allowed the analysis of hospital stay, taking into account that the censoring of cases due to death was not random. To predict the likelihood of intubation, we used the glm() function in R to fit a logistic regression model. For each model, we determined baseline demographic variables predictive of the outcomes and generated adjusted models. For variables with less than five cases per cell, we reported the p-values for Fisher's Exact Test.The analyses and results are published in:Chachkhiani, David et al. "Neurological complications in a predominantly African American population of COVID-19 predict worse outcomes during hospitalization." Clinical Neurology and Neurosurgery (in press).These data will be useful for researchers trying to build larger datasets regarding COVID19 neurological complications for metanalysis or to answer other questions requiring larger sample sizes.

Application of an evidence-based, out-patient treatment strategy for COVID-19: Multidisciplinary medical practice principles to prevent severe disease.

The COVID-19 pandemic has devastated individuals, families, and institutions throughout the world. Despite the breakneck speed of vaccine development, the human population remains at risk of further devastation. The decision to not become vaccinated, the protracted rollout of available vaccine, vaccine failure, mutational forms of the SARS virus, which may exhibit mounting resistance to our molecular strike at only one form of the viral family, and the rapid ability of the virus(es) to hitch a ride on our global transportation systems, means that we are will likely continue to confront an invisible, yet devastating foe. The enemy targets one of our human physiology's most important and vulnerable life-preserving body tissues, our broncho-alveolar gas exchange apparatus. Notwithstanding the fear and the fury of this microbe's potential to raise existential questions across the entire spectrum of human endeavor, the application of an early treatment intervention initiative may represent a crucial tool in our defensive strategy. This strategy is driven by evidence-based medical practice principles, those not likely to become antiquated, given the molecular diversity and mutational evolution of this very clever "world traveler".

Neurological complications in a predominantly African American sample of COVID-19 predict worse outcomes during hospitalization.

People with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, COVID-19, can have neurological problems including headache, anosmia, dysgeusia, altered mental status (AMS), ischemic stroke with or without large vessel occlusion, and Guillen-Barre Syndrome. Louisiana was one of the states hit hardest by the pandemic with just over 57,000 laboratory-confirmed cases of COVID-19 by the end of June 2020. We reviewed the electronic medical records (EMR) of patients hospitalized during the peak of the pandemic, March 1st through March 31st, to document the type and frequency of neurological problems seen in patients with COVID-19 at presentation to the emergency room. Secondary aims were to determine: 1) the frequency of neurological complaints during the hospital stay; 2) whether the presence of any neurological complaint at presentation or any of the individual types of neurological complaints at admission predicted three separate outcomes: death, length of hospital stay, or the need for intubation; and 3) if the presence of any neurological complaint or any of the individual types of neurological complaints developed during hospital stay predicted the previous three outcomes. A large proportion of our sample (80 %) was African American and had hypertension (79 %). Out of 250 patients, 56 (22 %) patients died, and 72 (29 %) patients required intubation. Thirty-four (14 %) had a neurological chief complaint at presentation; the most common neurological chief complaints in the entire sample were altered mental status (AMS) (8 %), headache (2 %), and syncope (2 %). We used a competing risk model to determine whether neurological symptoms at presentation or during hospital stay were predictors of prolonged hospital stay and death. To establish whether neurological symptoms were associated with higher odds of intubation, we used logistic regression. Age was the only significant demographic predictor of death and hospital stay. The HR (95 %CI) for remaining in the hospital for a ten-year increase in age was 1.2, (1.1, 1.3, p < 0.0001), and for death was 1.3, (1.1, 1.5, p < 0.01). There were no demographic characteristics, including age or comorbidities predictive of intubation. Adjusting for age, patients who at presentation had neurological issues as their chief complaint were at significantly increased risk for remaining in the hospital, HR = 1.7, (1.1,2.5, p = 0.0001), and dying, HR = 2.1(1.1,3.8, p = 0.02), compared to patients without any neurological complaint. Of the individual admission complaints, AMS was associated with a significantly prolonged hospital stay, HR = 1.8, (1.0-3.3, p = 0.05). Patients that required dialysis or intubation or had AMS during hospitalization had more extended hospital stays. After adjusting for age, dialysis, and intubation, patients with AMS during hospital stay had a HR of 1.6, (1.1, 2.5, p = 0.01) for remaining in the hospital. Patients who had statistically significant higher odds of requiring intubation were those who presented with any neurological chief complaint, OR = 2.8 (1.3,5.8, p = 0.01), or with headaches OR = 13.3 (2.1,257.0, p = 0.008). Patients with AMS during the hospital stay, as well as those who had seizures, were more likely to need intubation. In the multivariate model, dialysis, OR = 4.9 (2.6,9.4, p < 0.0001), and AMS, OR = 8.8 (3.9,21.2, p < 0.0001), were the only independent predictors of intubation. Neurological complaints at presentation and during the hospital stay are associated with a higher risk of death, prolonged hospital stay, and intubation. More work is needed to determine whether the cause of the neurological complaints was direct CNS involvement by the virus or the other systemic complications of the virus.

Part II. high-dose methotrexate with leucovorin rescue for severe COVID-19: An immune stabilization strategy for SARS-CoV-2 induced 'PANIC' attack.

Here, in Part II of a duology on the characterization and potential treatment for COVID-19, we characterize the application of an innovative treatment regimen for the prevention of the transition from mild to severe COVID-19, as well as detail an intensive immunotherapy intervention hypothesis. We propose as a putative randomized controlled trial that high-dose methotrexate with leucovorin (HDMTX-LR) rescue can abolish 'PANIC', thereby 'left-shifting' severe COVID-19 patients to the group majority of those infected with SARS-CoV-2, who are designated as having mild, even asymptomatic, disease. HDMTX-LR is endowed with broadly pleiotropic properties and is a repurposed, generic, inexpensive, and widely available agent which can be administered early in the course of severe COVID-19 thus rescuing the critical and irreplaceable gas-exchange alveoli. Further, we describe a preventative treatment intervention regimen for those designated as having mild to moderate COVID-19 disease, but who exhibit features which herald the transition to the severe variant of this disease. Both of our proposed hypothesis-driven questions should be urgently subjected to rigorous assessment in the context of randomized controlled trials, in order to confirm or refute the contention that the approaches characterized herein, are in fact capable of exerting mitigating, if not abolishing, effects upon SARS-CoV-2 triggered 'PANIC Attack'. Confirmation of our immunotherapy hypothesis would have far-reaching ramifications for the current pandemic, along with yielding invaluable lessons which could be leveraged to more effectively prepare for the next challenge to global health.

Part I. SARS-CoV-2 triggered 'PANIC' attack in severe COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has produced a world-wide collapse of social and economic infrastructure, as well as constrained our freedom of movement. This respiratory tract infection is nefarious in how it targets the most distal and highly vulnerable aspect of the human bronchopulmonary tree, specifically, the delicate yet irreplaceable alveoli that are responsible for the loading of oxygen upon red cell hemoglobin for use by all of the body's tissues. In most symptomatic individuals, the disease is a mild immune-mediated syndrome, with limited damage to the lung tissues. About 20% of those affected experience a disease course characterized by a cataclysmic set of immune activation responses that can culminate in the diffuse and irreversible obliteration of the distal alveoli, leading to a virtual collapse of the gas-exchange apparatus. Here, in Part I of a duology on the characterization and potential treatment for COVID-19, we define severe COVID-19 as a consequence of the ability of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to trigger what we now designate for the first time as a 'Prolific Activation of a Network-Immune-Inflammatory Crisis', or 'PANIC' Attack, in the alveolar tree. In Part II we describe an immunotherapeutic hypothesis worthy of the organization of a randomized clinical trial in order to ascertain whether a repurposed, generic, inexpensive, and widely available agent is capable of abolishing 'PANIC'; thereby preventing or mitigating severe COVID-19, with monumental ramifications for world health, and the global pandemic that continues to threaten it.

Dexamethasone as Abortive Treatment for Refractory Seizures or Status Epilepticus in the Inpatient Setting.

Refractory seizures or status epilepticus (RS/SE) continues to be a challenge in the inpatient setting. Failure to abort a seizure with antiepileptic drugs (AEDs) may lead to intubation and treatment with general anesthesia exposing patients to complications, extending hospitalization, and increasing the cost of care. Studies have shown a key role of inflammatory mediators in seizure generation and termination. We describe 4 patients with RS/SE that was aborted when dexamethasone was added to conventional AEDs: a 61-year-old female with temporal lobe epilepsy who presented with delirium, nonconvulsive status epilepticus, and oculomyoclonic status; a 56-year-old female with history of traumatic left frontal lobe hemorrhage who developed right face and hand epilepsia partialis continua followed by refractory focal clonic seizures; a 51-year-old male with history of traumatic intracranial hemorrhage who exhibited left-sided epilepsia partialis continua; and a 75-year-old female with history of breast cancer who manifested nonconvulsive status epilepticus and refractory focal clonic seizures. All patients continued experiencing RS/SE despite first- and second-line therapy, and one patient continued to experience RS/SE despite third-line therapy. Failure to abort RS/SE with conventional therapy motivated us to administer intravenous dexamethasone. A 10-mg load was given (except in one patient) followed by 4.0- 5.2 mg q6h. All clinical and electrographic seizures stopped 3-4 days after starting dexamethasone. When dexamethasone was discontinued 1-3 days after seizures stopped, all patients remained seizure-free on 2-3 AEDs. The cessation of RS/SE when dexamethasone was added to conventional antiseizure therapy suggests that inflammatory processes are involved in the pathogenesis of RS/SE.

A comparison of anticonvulsants in the treatment of impulsive aggression.

This study compared the behavioral effects of 3 anticonvulsants in impulsive aggressive men. In a double-blind, placebo-controlled, parallel groups design, participants were randomly assigned to 1 of 4 6-week treatments: phenytoin (n = 7), carbamazepine (n = 7), valproate (n = 7), or placebo (n = 8). The efficacy measure was the average aggression score, a global severity index from the Overt Aggression Scale (J. M. Silver & S. C. Yudofsky, 1991). Analysis showed a significant reduction in impulsive aggression during all 3 anticonvulsant conditions compared with placebo. However, the treatment effect during carbamazepine administration was slightly delayed compared with phenytoin and valproate. These findings suggest that increased use of anticonvulsants could make a significant impact in the control of impulsive aggression in both mental health and criminal justice settings.

Characterizing aggressive behavior.

In the research literature, aggressive behavior has traditionally been classified into two distinct subtypes, impulsive or premeditated. Impulsive aggression is defined as a hair-trigger aggressive response to provocation with loss of behavioral control. Premeditated aggression is defined as a planned or conscious aggressive act, not spontaneous or related to an agitated state. The present study outlines the development of a clinically useful self-report instrument, the Impulsive/Premeditated Aggression Scales (IPAS), designed to characterize aggressive behavior as predominately impulsive or predominately premeditated in nature. The IPAS showed strong reliability and validity. Analysis of the IPASscores demonstrated thepresence of two types of aggressive behavior, impulsive and premeditated, in men referred for anger problems. The aggression of most individuals in the present sample was characterized as predominately impulsive in nature (90%).

Obsessive-compulsive personality disorder and behavioral disinhibition.

Although obsessive-compulsive personality disorder (OCPD) is an Axis II diagnosis that is not commonly associated with behavioral disinhibition, the literature contains reports of occasional explosive aggressive outbursts. Existing explanations of OCPD etiology do not address the coexistence of compulsive and impulsive features witnessed in some subpopulations of patients. In this study, the authors present a compensatory theory of OCPD in an effort to explain clinical observations of an unexpectedly large number of OCPD diagnoses among patients clinic referred and self-referred for aggression problems.

Unihemispheric burst suppression.

Burst suppression (BS) consists of bursts of high-voltage slow and sharp wave activity alternating with periods of background suppression in the electroencephalogram (EEG). When induced by deep anesthesia or encephalopathy, BS is bihemispheric and is often viewed as a non-epileptic phenomenon. In contrast, unihemispheric BS is rare and its clinical significance is poorly understood. We describe here two cases of unihemispheric BS. The first patient is a 56-year-old woman with a left temporoparietal tumor who presented in convulsive status epilepticus. EEG showed left hemispheric BS after clinical seizure termination with lorazepam and propofol. The second patient is a 39-year-old woman with multiple medical problems and a vague history of seizures. After abdominal surgery, she experienced a convulsive seizure prompting treatment with propofol. Her EEG also showed left hemispheric BS. In both cases, increasing the propofol infusion rate resulted in disappearance of unihemispheric BS and clinical improvement. The prevailing view that typical bihemispheric BS is non-epileptic should not be extrapolated automatically to unihemispheric BS. The fact that unihemispheric BS was associated with clinical seizure and resolved with propofol suggests that, in both cases, an epileptic mechanism was responsible for unihemispheric BS.

Sporadic Creutzfeldt-Jakob disease with focal findings: caveats to current diagnostic criteria.

The clinical diagnosis of Creutzfeldt-Jakob disease (CJD) is largely based on the 1998 World Health Organization diagnostic criteria. Unfortunately, rigid compliance with these criteria may result in failure to recognize sporadic CJD (sCJD), especially early in its course when focal findings predominate and traditional red flags are not yet present. A 61-year-old man presented with a 3-week history of epilepsia partialis continua (jerking of the left upper extremity) and a 2-week history of forgetfulness and left hemiparesis; left hemisensory neglect was also detected on admission. Repeated brain magnetic resonance imaging (MRI) showed areas of restricted diffusion in the cerebral cortex, initially on the right but later spreading to the left. Electroence-phalography (EEG) on hospital days 7, 10, and 14 showed right-sided periodic lateralized epileptiform discharges. On day 20, the EEG showed periodic sharp wave complexes leading to a diagnosis of probable sCJD and subsequently to definite sCJD with brain biopsy. Neurological decline was relatively fast with generalized myoclonus and akinetic mutism developing within 7 weeks from the onset of illness. CJD was not immediately recognized because of the patient's focal/lateralized manifestations. Focal/lateralized clinical, EEG, and MRI findings are not uncommon in sCJD and EEG/MRI results may not be diagnostic in the early stages of sCJD. Familiarity with these caveats and with the most current criteria for diagnosing probable sCJD (University of California San Francisco 2007, MRI-CJD Consortium 2009) will enhance the ability to recognize sCJD and implement early safety measures.

Botulinum toxin injections for simple partial motor seizures associated with pain.

Intractable epilepsy with painful partial motor seizures is a relatively rare and difficult disorder to treat. We evaluated the usefulness of botulinum toxin to reduce ictal pain. Two patients received two or four botulinum toxin (BTX) injections at one-to-two-month intervals. Patient 1 had painful seizures of the right arm and hand. Patient 2 had painful seizures involving the left foot and leg. Injections were discontinued after improved seizure control following resective surgery. Both patients received significant pain relief from the injections with analgesia lasting at least two months. Seizure severity was reduced, but seizure frequency and duration were unaffected. For these patients, BTX was effective in temporarily relieving pain associated with muscle contraction in simple partial motor seizures. Our findings do not support the hypothesis that modulation of motor end-organ feedback affects focal seizure generation. BTX is a safe and reversible treatment that should be considered as part of adjunctive therapy after failure to achieve control of painful partial motor seizures.

Typical Spike-and-Wave Activity in Hypoxic-Ischemic Brain Injury and its Implications for Classifying Nonconvulsive Status Epilepticus.

INTRODUCTION: Typical spike-and-wave activity (TSWA) in the electroencephalogram (EEG) indicates idiopathic generalized epilepsy (IGE). IGE-related nonconvulsive status epilepticus (NCSE) is typically an absence status epilepticus (ASE). ASE and TSWA respond dramatically to benzodiazepines. Patients with no history of seizure/epilepsy may develop ASE "de novo" in the context of an acute brain disorder. However, we are aware of only one previous case of de novo ASE with TSWA in hypoxic-ischemic brain injury. CASE PRESENTATION: A 65-year-old man, with congestive heart failure and history of substance abuse, survived cardiorespiratory arrest after 18 minutes of cardiopulmonary resuscitation. Post-resuscitation, the patient was in coma with intact brainstem function. Toxicology was positive for cocaine and marijuana. Eyelid myoclonus suggested NCSE, which was initially treated with lorazepam and fosphenytoin. EEG monitoring showed sustained TSWA confirming NCSE and demonstrating de novo ASE (the patient and his family never had seizure/epilepsy). The TSWA was resistant to lorazepam, levetiracetam, and low-dose midazolam; it was eliminated only with midazolam at a dose that resulted in burst-suppression (≥1.2 mg/kg/hour). CONCLUSION: This is an unusual case of TSWA and hypoxic-ischemic brain injury in a patient with no history of seizure/epilepsy. The TSWA was relatively resistant to benzodiazepines suggesting that cerebral hypoxia-ischemia spared the thalamocortical apparatus generating TSWA but impaired the cortical/thalamic inhibitory circuits where benzodiazepines act to suppress TSWA. Albeit rare, 'post-hypoxic' TSWA offers us some valuable insights for classifying and managing nonconvulsive status epilepticus.