Kevin Chapman

Interobserver agreement in the interpretation of EEG patterns in critically ill adults.

Summary: The significance of rhythmic and periodic EEG patterns in critically ill patients is unclear. A universal terminology is needed to facilitate study of these patterns, and consistent observer agreement should be demonstrated in its use. The authors evaluated inter- and intraobserver agreement using the standardized terminology (Hirsch et al., J Clin Neurophysiol 2005;22:128–135) recently proposed by the American Clinical Neurophysiology Society. Trained electroencephalographers viewed a series of 10-second EEG samples from critically ill adults (phase I), a set of ≥20-minute EEGs from the same patient cohort (phase II), and then reevaluated the first sample set (phase III). The readers used the proposed terminology to “score” each EEG. For each possible term, interobserver agreement (phases I and II) and intraobserver agreement (phase III) were calculated using pairwise kappa (&kgr;) values. Moderate agreement beyond chance was seen for the presence/absence of rhythmic or periodic patterns and for localization of these patterns. Agreement for other terms was slight to fair. Inter- and intraobserver agreement were consistently lower for optional terms than mandatory terms. Even when standardized terminology is used, the description of rhythmic and periodic EEG patterns varies significantly. Further refinement of the proposed terminology is required to improve inter- and intraobserver agreement.

Seizure outcome and complications following hypothalamic hamartoma treatment in adults: endoscopic, open, and Gamma Knife procedures

OBJECTnThis study aimed at identifying outcomes with respect to seizures, morbidity, and mortality in adult patients undergoing resective or Gamma Knife surgery (GKS) to treat intractable epilepsy associated with hypothalamic hamartoma (HH).nnnMETHODSnAdult patients undergoing surgical treatment for HH-related epilepsy were prospectively monitored at a single center for complications and seizure outcome by using a proprietary database. Preintervention and postintervention data for patients 18 years of age and older, and with at least 1 year of follow-up, were analyzed, with specific attention to seizure control, complications, hormonal status, and death.nnnRESULTSnForty adult patients were found in the database (21 were women). The median HH volume was 0.54 cm(3). In 70% of patients, it was located inside the third ventricle, attached unilaterally and vertically to the hypothalamus (Delalande Type II). Most patients (26) underwent an endoscopic resection, 10 patients had a transcallosal or other type of open (pterional or orbitozygomatic) resection, and 4 patients chose GKS. Twenty-nine percent became seizure free in the long term, and overall a majority of patients (55%) reported at least > 90% seizure improvement. Only 3 patients were ultimately able to discontinue anticonvulsants, whereas most patients were taking an average of 2 antiepileptic drugs pre- and postoperatively. The only factor significantly correlated with seizure-free outcome was the absence of mental retardation. The HH volume, HH type, and amount of resection or disconnection were not correlated to seizure freedom. A total of 4 patients (10%) died, 2 immediately after surgery and 2 later. All of them had undergone a resection, as opposed to GKS, and still had seizures. Postoperatively, persistent neurological deficits were seen in 1 patient; 34% of patients had mild hormonal problems; and 59% experienced weight gain of at least 6.8 kg (average gain 12.7 kg).nnnCONCLUSIONSnSurgical or GKS procedures in adults with HH provided seizure freedom in one-third of patients. The only significant favorable prognostic factor was the absence of mental retardation. The overall mortality rate was high, at 10%. Other important morbidities were persistent hormonal disturbances and weight gain.

Incidence of seizures on continuous EEG monitoring following traumatic brain injury in children

OBJECT Seizures may cause diagnostic confusion and be a source of metabolic stress after traumatic brain injury (TBI) in children. The incidence of electroencephalography (EEG)-confirmed seizures and of subclinical seizures in the pediatric population with TBI is not well known. METHODS A routine protocol for continuous EEG (cEEG) monitoring was initiated for all patients with moderate or severe TBI at a Level 1 pediatric trauma center. Over a 3.5-year period, all patients with TBI who underwent cEEG monitoring, both according to protocol and those with mild head injuries who underwent cEEG monitoring at the discretion of the treating team, were identified prospectively. Clinical data were collected and analyzed. RESULTS Over the study period, 594 children were admitted with TBI, and 144 of these children underwent cEEG monitoring. One hundred two (71%) of these 144 children had moderate or severe TBI. Abusive head trauma (AHT) was the most common mechanism of injury (65 patients, 45%) in children with cEEG monitoring. Seizures were identified on cEEG in 43 patients (30%). Forty (93%) of these 43 patients had subclinical seizures, including 17 (40%) with only subclinical seizures and 23 (53%) with both clinical and subclinical seizures. Fifty-three percent of patients with seizures experienced status epilepticus. Age less than 2.4 years and AHT mechanism were strongly correlated with presence of seizures (odds ratios 8.7 and 6.0, respectively). Those patients with only subclinical seizures had the same risk factors as the other groups. The presence of seizures did not correlate with discharge disposition but was correlated with longer hospital stay and intensive care unit stay. CONCLUSIONS Continuous EEG monitoring identifies a significant number of subclinical seizures acutely after TBI. Children younger than 2.4 years of age and victims of AHT are particularly vulnerable to subclinical seizures, and seizures in general. Continuous EEG monitoring allows for accurate diagnosis and timely treatment of posttraumatic seizures, and may mitigate secondary injury to the traumatized brain.

Catastrophic demyelinating encephalomyelitis after intrathecal and intravenous stem cell transplantation in a patient with multiple sclerosis.

Stem cell transplantation is an investigational therapy for multiple sclerosis. The authors describe a case of catastrophic demyelinating encephalomyelitis following stem cell transplantation in a 17-year-old girl. Nine months after an initial diagnosis of multiple sclerosis, she underwent stem cell transplantation in Costa Rica. Subsequently, she deteriorated and was transported back to the United States with headache and vomiting progressing to quadriparesis, locked-in syndrome, and superimposed encephalopathy. Magnetic resonance imaging and brain biopsy were consistent with fulminant demyelinating encephalomyelitis with enhancing parenchyma and leptomeninges. Cerebrospinal fluid analysis revealed lymphocytic pleocytosis and high protein. The protracted illness required tracheostomy and gastrostomy. After methyleprednisone, intravenous immunoglobulin, and cyclophosphamide, she improved during 2.5 months to an ambulatory, functionally independent state. Subsequently, typical less severe multiple sclerosis relapses occurred. This case demonstrates that stem cell transplantation may provoke life-threatening encephalomyelitis in patients with multiple sclerosis. This highlights the need to restrict transplantation to trials with appropriate safety controls.

EEG and video-EEG seizure monitoring has limited utility in patients with hypothalamic hamartoma and epilepsy

Purpose:u2002 Hypothalamic hamartomas (HHs) are a malformation of the ventral hypothalamus and tuber cinereum, associated with gelastic seizures and epilepsy. We sought to determine the spectrum of electroencephalography (EEG) abnormalities in a large cohort of HH patients.

Ketogenic diet in the treatment of seizures associated with hypothalamic hamartomas

Seizures associated with hypothalamic hamartoma (HH) are notoriously intractable to medical therapy, and while surgical resection affords most affected patients with complete or near seizure-freedom, there remains a need to identify alternative treatments. In this retrospective study, we identified six patients from a large cohort of 220 patients with HH who were treated with the ketogenic diet (KD). Four patients had a 50-90% reduction in multiple seizure types (including gelastic, partial-onset and atonic seizures), and two individuals failed to respond. In order to study possible mechanisms, we then performed microelectrode recordings of small neurons in surgically resected HH tissue slices. Exposure to ketone bodies decreased spontaneous firing in 5 of 7 small HH neurons. These preliminary results suggest that seizures associated with HH may respond favorably to the KD, and that ketone bodies might directly modulate the intrinsic epileptogenicity of HH tissue.

Rhythmical and periodic EEG patterns do not predict short-term outcome in critically ill patients with subarachnoid hemorrhage.

Introduction: Nonconvulsive seizures and nonconvulsive status epilepticus commonly occur in patients with aneurysmal subarachnoid hemorrhages. When continuous EEG is used in patients in the neuro-intensive care unit, rhythmical and periodic patterns of uncertain significance are frequently encountered. It is unknown how these findings impact patient outcome. Methods: Patients were enrolled from a single tertiary care center with subarachnoid hemorrhages secondary to ruptured intracranial aneurysm, and either a witnessed seizure or significantly impaired mental status. Prospective clinical, laboratory, imaging, and short-term outcome data were collected. Continuous EEG monitoring was performed and scored according to American Clinical Neurophysiology Society (ACNS) Subcommittee on Research Terminology for Continuous EEG Monitoring. Results: Sixty-eight patients were enrolled. Fifty-four had a poor-grade subarachnoid hemorrhage upon admission. Fifty-one patients had rhythmical or periodic patterns: 33 with periodic discharges and 38 with rhythmic delta activity. Four patients had unequivocal electrographic seizures. Patients did poorly in the short term: 14 died and 42 were severely disabled at discharge. In hospital, mortality was 19.6% in patients with rhythmical or periodic patterns and 23.5% in patients without. Age, female gender, and endovascular treatment had a positive correlation with the occurrence of periodic discharges. However, there was no correlation between rhythmical and periodic patterns and outcome. Discussion: Using the ACNS Research Terminology, it is shown that rhythmical and periodic patterns are very common in critically ill patients with subarachnoid hemorrhage. However, the presence and the abundance of these patterns did not predict short-term outcome in this prospective, single-center observational study. We were unable to show that rhythmical and periodic EEG patterns are an independent predictor for outcome relative to other clinical features. Large multicenter studies will be required to determine if these patterns independently predict outcome and to demonstrate the impact of treatment interventions that are directed at rhythmical and periodic continuous EEG patterns.

Utility and safety of prolonged video-EEG monitoring in a tertiary pediatric epilepsy monitoring unit☆

Prolonged video-EEG (vEEG) monitoring helps characterize paroxysmal events and epilepsy. There is limited literature in pediatrics describing the safety and utility of vEEG. We retrospectively reviewed 454 pediatric epilepsy monitoring unit admissions over two years. Final event diagnoses, duration of seizures, and medical complications were analyzed. Two hundred twenty admissions (48.4%) captured epileptic seizures, 150 (33.0%) captured nonepileptic events, and 84 (18.5%) failed to capture any events. Medical complications were seen in 4 patients (1.8%) with no long-term complications. Seventeen episodes of status epilepticus occurred in 13 patients. This constituted 2.9% of all admissions and 5.9% of admissions with epileptic seizures. The median duration of status was 26 min, and three patients required transfer to the pediatric intensive care unit. Video-EEG monitoring had a high yield in capturing events and differentiating epileptic from nonepileptic events. Our pediatric patients experienced greater risk of status epilepticus but lesser risk of injury.

Hemimegalencephaly in a Patient With a Neurocutaneous Syndrome

A 5-year-old girl with a history of hypomelanosis of Ito and intractable epilepsy was evaluated for possible resective surgery. Magnetic resonance imaging showed an enlarged right hemisphere, whereas electrographic seizures were arising from the right hemisphere or had a generalized onset. The patient was believed to be a good candidate for hemispherectomy, but the family was hesitant and started a modified Atkins diet. Her seizure control has improved, but she continues to have weekly seizures. Hypomelanosis of Ito is a well-known cause of hemimegalencephaly and is often associated with intractable epilepsy and hemiparesis. Hemispherectomy can often be an effective treatment in intractable cases.

The challenge of treating spikes.

Interictal spikes are a hallmark of epilepsy that assist with classification and treatment, but we rarely actually treat interictal spikes. The exception is epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS), also characterized in the literature as electrical status epilepticus during slow sleep (ESES). This entity consists of a combination of neuropsychological impairment associated with a significant increase in the frequency of spikes during sleep. The definition of the syndrome is not agreed on, and inconsistent terminology (ESES versus CSWS), inclusion criteria, treatment, and outcome in various studies leave the clinician uncertain about whom to treat and which treatment is best. A recent survey demonstrated that many clinicians use different electroencephalogram (EEG) and clinical criteria in treating the same syndrome.1 The pathophysiology of CSWS is unclear but likely involves corticothalamic neurotransmission. Individuals with a thalamic injury, particularly one involving the reticular nucleus of the thalamus, have a higher incidence of developing CSWS. This may in turn alter the inhibitory GABA network and lead to increased spiking during sleep. Such an alteration could also explain why GABA-ergic agents, such as benzodiazepines, may be effective. Some case series have found copy number variations or genetic mutations in patients with CSWS, but these associations are as yet unproven. The optimal treatment of CSWS remains uncertain because recommendations are derived primarily from limited case series data. Clinical studies have used different anticonvulsants, benzodiazepines, and steroidswith varying results and lack of clearly superior treatment. Most authors recommend avoiding anticonvulsants that are primarily effective for partial seizures (e.g., carbamazepine). Typical medications used to treat seizures are not particularly effective in treating interictal spikes, reminding us that our current anticonvulsants are not antiepileptogenic. The necessary duration of treatment is also debated. Some clinicians advocate shorter courses of therapy, increasing the risk for relapse, whereas others suggest prolonged treatment.