Adithya Sivaraju

Understanding and Managing the Ictal-Interictal Continuum in Neurocritical Care

Opinion statementContinuous electroencephalographic (EEG) monitoring has become an invaluable tool for the assessment of brain function in critically ill patients. However, interpretation of EEG waveforms, especially in the intensive care unit (ICU) setting is fraught with ambiguity. The term ictal-interictal continuum encompasses EEG patterns that are potentially harmful and can cause neuronal injury. There are no clear guidelines on how to treat EEG patterns that lie on this continuum. We advocate the following approaches in a step wise manner: (1) identify and exclude clear electrographic seizures and status epilepticus (SE), i.e., generalized spike-wave discharges at 3/s or faster; and clearly evolving discharges of any type (rhythmic, periodic, fast activity), whether focal or generalized; (2) exclude clear interictal patterns, i.e., spike-wave discharges, periodic discharges, and rhythmic patterns at 1/s or slower with no evolution, unless accompanied by a clear clinical correlate, which would make them ictal regardless of the frequency; (3) consider any EEG patterns that lie in between the above two categories as being on the ictal-interictal continuum; (4) compare the electrographic pattern of the ictal-incterictal continuum to the normal background and unequivocal seizures (if present) from the same patient; (5) when available, correlate ictal-interictal continuum pattern with other markers of neuronal injury such as neuronal specific enolase (NSE) levels, brain imaging findings, depth electrode recordings, data from microdialysis, intracranial pressure fluctuations, and brain oxygen measurement; and (6) perform a diagnostic trial with preferably a nonsedating antiepileptic drug with the endpoint being both clinical and electrographic improvement. Minimize the use of anesthetics or multiple AEDs unless there is clear supporting evidence from ancillary tests or worsening of the EEG patterns over time, which could indicate possible neuronal injury.

Human bedside evaluation versus automatic responsiveness testing in epilepsy (ARTiE)

Evaluation of behavioral impairment during epileptic seizures is critical for medical decision making, including accurate diagnosis, recommendations for driving, and presurgical evaluation. We investigated the quality of behavioral testing during inpatient video–electroencephalography (EEG) monitoring at an established epilepsy center, and introduce a technical innovation that may improve clinical care. We retrospectively reviewed video‐EEG data from 152 seizures in 33 adult or pediatric patients admitted for video‐EEG monitoring. Behavioral testing with questions or commands was performed in only 50% of seizures ictally, 73% of seizures postictally, and 80% with either ictal or postictal testing combined. Furthermore, the questions or commands were highly inconsistent and were performed by nonmedical personnel in about one fourth of cases. In an effort to improve this situation we developed and here introduce Automatic Responsiveness Testing in Epilepsy (ARTiE), a series of video‐recorded behavioral tasks automatically triggered to play in the patients room by computerized seizure detection. In initial technical testing using prerecorded or live video‐EEG data we found that ARTiE is initiated reliably by automatic seizure detection. With additional clinical testing we hope that ARTiE will succeed in providing comprehensive and reliable behavioral evaluation during seizures for people with epilepsy to greatly improve their clinical care.

Substantial and sustained seizure reduction with ketogenic diet in a patient with Ohtahara syndrome

Ketogenic diet has been shown to be efficacious in some epileptic encephalopathies but rarely reported as being useful in children with Ohtahara syndrome. This could possibly be attributed to the rarity of the disease and associated short survival period. We report on a 5-year-old child with Ohtahara syndrome, whose seizures failed to improve with all known medications, continued to show persistent suppression-burst pattern on the electroencephalography (EEG) and had substantial reduction in seizure frequency for one year post-initiation of ketogenic diet. He has not had a single visit to the emergency room because of seizures in the last one year, and more importantly, there has been a clear improvement noted in his level of interaction and temperament. Patients with Ohtahara syndrome invariably have medically intractable seizures and catastrophic neurodevelopmental outcome. Ketogenic diet is a treatment modality that might be worth considering even in this group of patients.

Cyclic seizures in critically ill patients: Clinical correlates, DC recordings and outcomes

OBJECTIVE To describe EEG and clinical correlates, DC recordings and prognostic significance of cyclic seizures (CS). METHODS We reviewed our prospective continuous EEG database to identify patients with CS, controls with non-cyclic status epilepticus (SE) and controls without seizure matched for age and etiology. EEG was reviewed with DC settings. RESULTS 39/260 (15%) patients with electrographic seizures presented with CS. These patients were older (62 vs. 54years; p=0.04) and more often had acute or progressive brain injury (77% vs. 52%; p=0.03) than patients with non-cyclic SE and had a lower level of consciousness, were more severely ill, than matched controls. CS almost always had focal onset, often from posterior regions. Patients with CS trended towards worse prognosis. When available (12 patients), DC recordings showed an infraslow cyclic oscillation of EEG baseline synchronized to the seizures in all cases. CONCLUSIONS CS occur mostly in older patients with acute or progressive brain injury, are more likely to be associated with poor outcome than patients with other forms of nonconvulsive SE, and are accompanied by synchronous oscillations of the EEG baseline on DC recordings. SIGNIFICANCE CS are a common form of non-convulsive status epilepticus in critically ill patients and provide further insights into the relationship between infraslow activity and seizures; further study on this relationship may shed light on the mechanisms of seizure initiation and termination.

Stroke after Initiating IV Penicillin for Neurosyphilis: A Possible Jarisch-Herxheimer Reaction

Introduction. Syphilis incidence has increased in the US in the last decade. Jarisch-Herxheimer reaction (JHR) is a well-documented adverse effect of penicillin treatment in syphilis. Stroke has not been reported as part of its phenomenology. Case Report. A 57-year-old man presented with worsening memory. His minimental status examination score was 14/30. Serum RPR test was positive and VDRL test in the CSF was reactive. Within six hours of first dose of IV crystalline penicillin G, he was found to have hemineglect and difficulty moving the left leg. MRI of the brain showed multiple acute ischemic strokes. Immediate MRA ruled out vascular occlusion. Penicillin treatment was stopped. Four hours later, he was found to be febrile and had two episodes of generalized tonic-clonic seizures. Conclusions. We report a case of confirmed neurosyphilis with no known modifiable stroke risk factors, who developed acute ischemic stroke and other constitutional symptoms consistent with JHR after IV penicillin. This is the first reported case in literature where an acute ischemic stroke can be attributed to Jarisch-Herxheimer reaction. Given an increase in incidence of syphilis in recent years, our case underlies the importance of keeping in mind potential catastrophic drug adverse reactions in neurosyphilis patients.

Drop attacks: A clinical manifestation of LGI1 encephalitis

We describe a clinical manifestation of leucine-rich glioma-inactivated-1 (LGI1) encephalitis. The patient was a 90-year-old woman, independent at baseline, with a medical history of hypertension. Two months prior to admission, she had an unwitnessed fall and was found after an unknown period of unconsciousness. She was taken to an outside hospital where rhabdomyolysis (creatine kinase >16,000, reference 24–170 U/L) was documented. During that admission, she had a witnessed generalized tonic-clonic seizure. Prolonged EEG video monitoring captured multiple episodes of right leg jerking without a change in her consciousness or an abnormal EEG correlate. Interictal EEG findings were unremarkable. A metabolic panel showed mild hyponatremia (133; reference 137–145 mmol/L). MRI of the brain was unremarkable. CSF analysis was normal (leukocytes 3/mm3, protein 45 mg/dL, and glucose 80 mg/dL). She was discharged home on levetiracetam (1,500 mg daily) and did not have any further documented convulsions, but reported hypersomnolence.