Brian D. Moseley

How common is ictal hypoxemia and bradycardia in children with partial complex and generalized convulsive seizures

Purpose:  Autonomic effects of seizures, including cardiorespiratory abnormalities, may be involved in sudden unexpected death in epilepsy (SUDEP). The purpose of this study was to determine the prevalence and risk factors for ictal hypoxemia (oxygen saturation <90%) and ictal bradycardia (heart rate < second percentile for age) in children during recorded seizures.

Electrocardiographic and oximetric changes during partial complex and generalized seizures

Significant autonomic changes occur during seizures and may be related to sudden unexplained death in epilepsy (SUDEP). Accordingly, we performed a study to determine the prevalence of heart rate, QTc, and oximetric changes during seizures and analyzed their association with SUDEP risk factors. We analyzed 218 seizures from 76 patients. Ictal sinus tachycardia occurred in 57% of seizures and was associated with ≥3 failed AEDs (p=0.001), generalized seizures (p<0.001), and normal brain MRI (p=0.04). Ictal sinus bradycardia was rare, occurring in 2% of seizures. Ictal bradycardia was associated with seizure clustering (p=0.028) and reported history of ≥50 seizures/month (p=0.01). Depending on the correction formula utilized for calculating QTc, clinically significant ictal QTc prolongation (≥460ms for children ≤13 years, ≥470ms for males age >13, and ≥480ms for females age >13) occurred in 4.8-16.2% of seizures, while ictal QTc prolongation ≥500ms occurred in 2.9-16.2%. Ictal QTc shortening ≤340ms was observed in 3.8-4.8% of seizures. Ictal hypoxemia occurred in 25% of seizures and was associated with normal MRI (p=0.01), longer seizure duration (p=0.049), and ictal tachycardia (p=0.003). Such findings may have implications for understanding the pathogenesis of SUDEP.

Autonomic epileptic seizures, autonomic effects of seizures, and SUDEP

Many generalized tonic-clonic seizures are accompanied by profound autonomic changes. However, autonomic seizures and autonomic status epilepticus can also be seen with specific electroclinical syndromes (Panayiotopoulos syndrome), etiologies, and localizations. Such autonomic symptoms may impact cardiorespiratory function. While it is likely that several factors contribute to SUDEP, further study of both ictal respiratory and cardiac changes and underlying neuroanatomical mechanisms involved in autonomic seizure semiology are likely to provide important data to improve our understanding of the pathophysiology of this devastating condition. This paper will review the association between autonomic symptoms and epileptic seizures and will highlight the work of three young investigators. Drs. Lisa Bateman and Brian Moseley will review their work on cardiorespiratory effects of recorded seizures and how this assists in our understanding of SUDEP. Dr. John Millichap will review autonomic seizures and autonomic dysfunctions related to childhood epilepsy and will discuss the importance of expanded research efforts in this field.

N-methyl-D-aspartate Receptor Autoimmune Encephalitis Presenting With Opsoclonus-Myoclonus: Treatment Response to Plasmapheresis

OBJECTIVES To report the clinical, laboratory, and radiographic features and the response to plasmapheresis in a patient with encephalopathy, opsoclonus, and myoclonus whose cerebrospinal fluid was positive for N-methyl-D-aspartate receptor-IgG. DESIGN Case report. SETTING St Marys Hospital, Rochester, Minnesota. PATIENT A 27-year-old woman with a history of episodic migraine developed subacute progressive myoclonus, opsoclonus, and encephalopathy. RESULTS Magnetic resonance imaging demonstrated nodular leptomeningeal enhancement in the superior cerebellar folia and subsequent T2 hyperintensities in the periventricular regions and amygdala. A positron emission tomographic scan of the head demonstrated predominantly frontotemporoparietal cortical hypometabolism with sparing of the primary sensory and motor cortices. Cerebrospinal fluid examination revealed a lymphocytic pleocytosis, mildly elevated protein level, elevated IgG index, and positive oligoclonal banding. Autoimmune cerebrospinal fluid screening revealed a neural-specific IgG that bound to synapse-rich regions of mouse hippocampus and cerebellar granular layer; the neural-specific IgG was confirmed to be N-methyl-D-aspartate receptor specific. No neoplasm was detected by physical examination or by whole-body computed tomography and positron emission tomography. A 5-day course of high-dose intravenous methylprednisolone sodium succinate yielded limited improvement, and the patient subsequently required intensive care unit admission following a pulseless electrical activity arrest associated with pulmonary embolism. The encephalopathy improved dramatically after plasmapheresis. CONCLUSIONS This case highlights opsoclonus and myoclonus as manifestations of autoimmune N-methyl-D-aspartate receptor encephalitis in the setting of a novel appearance on positron emission tomography, and it shows a remarkable clinical response to plasmapheresis.

The treatment of ictal asystole with cardiac pacing

Ictal asystole may contribute to seizure‐related injury and mortality. The purpose of this study was to evaluate the effect of cardiac pacing on seizure‐related injury rates in ictal asystole patients. A survey was conducted to determine seizure‐related fall rate and other morbidity in all seven patients with ictal asystole who underwent cardiac pacing at our institution between 1990 and 2004. The rate of seizure‐related falls and other morbidities before and after pacing were compared using the Wilcoxon rank‐sum test. The mean fall rate was 3.28 falls/month pre‐pacemaker implantation. Following pacemaker implantation, this was reduced to 0.005 falls/month (p = 0.001). Seizure‐related fractures and motor vehicle accidents were also reduced following cardiac pacing. These findings may have implications in mitigating the potential morbidity associated with ictal asystole.

Historic, Clinical, and Prognostic Features of Epileptic Encephalopathies Caused by CDKL5 Mutations

Mutations within the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene are important causes of early-onset epileptic encephalopathies. We sought to determine the historic, clinical, and prognostic features of epilepsy secondary to CDKL5 mutations. We performed retrospective chart reviews of children at our institution with epilepsy and CDKL5 mutations. Six children were identified. One manifested a deletion in exons 10-15 of the CDKL5 gene, another manifested a single base-pair duplication in exon 3, and the rest manifested base-pair exchanges. The mean age of seizure onset was 1.8 months (range, 1-3 months). Although the majority (4/6, 67%) presented with partial-onset seizures, all children developed infantile spasms. All children demonstrated developmental delay and visual impairment. Although such mutations are X-linked, two children were boys. They did not present with more severe phenotypes than their female counterparts. Despite trials of antiepileptic drugs (mean, 5; range, 3-7), steroids/adrenocorticotropic hormone (4/6; 67%), and the ketogenic diet (6/6; 100%), all children manifested refractory seizures at last follow-up. Although no treatment eliminated seizures, topiramate, vigabatrin, and the ketogenic diet were most helpful at reducing seizure frequency.

A population-based study of long-term outcome of epilepsy in childhood with a focal or hemispheric lesion on neuroimaging

Purpose:  To evaluate long‐term seizure outcome in children with epilepsy and a focal or hemispheric neuroimaging abnormality.

Characteristics of postictal generalized EEG suppression in children

Although the pathophysiologic mechanism of sudden unexpected death in epilepsy (SUDEP) is unknown, autonomic dysfunction is thought to be the most likely. It has been hypothesized that respiratory depression resulting in SUDEP may be secondary to postictal generalized electroencephalography suppression (PGES). We sought to determine the characteristics of PGES in children. This included whether PGES was associated with ictally mediated autonomic changes and potential increased risk of SUDEP. Children admitted to our Pediatric Epilepsy Monitoring Unit between 3/2009 and 10/2011 were prospectively recruited. Clinical and electrophysiological data from children with PGES were compared to those without PGES. Data included the occurrence of peri-ictal tachycardia, bradycardia, and hypoxemia. Potential SUDEP risk was assessed using SUDEP-7 Inventory scores. Thirty seven children with 168 seizures were analyzed. PGES was observed following 27/168 (16.1%) seizures in 12/37 (32.4%) children. Only primary and secondarily generalized tonic clonic seizures were marked by PGES. PGES was significantly associated with peri-ictal tachycardia (p=0.019) and hypoxemia (p=0.005). Children with PGES had significantly higher SUDEP-7 Inventory scores than those without PGES (4.2 ± 1.3 versus 2.8 ± 1.4, p=0.007). SUDEP-7 scores were not significantly different between children with and without peri-ictal tachycardia (3.4 ± 1.3 versus 2.5±1.6, p=0.12), bradycardia (4 ± 2 versus 2.9 ± 1.4, p=0.45), or hypoxemia (3.4 ± 1.5 versus 2.4 ± 1.3, p=0.051). Based on our data, PGES is not rare in children. Children with PGES may be at greater risk for SUDEP as measured by the SUDEP-7 Inventory.

Contralateral cutaneous and MRI findings in a patient with Parry–Romberg syndrome

A 23-year-old man was admitted for management of simple partial status epilepticus. He was diagnosed with Parry–Romberg syndrome at the age of 5 years after developing left hemifacial atrophy (figure 1A). Biopsy of a focally hyperpigmented depressed plaque of his left ear showed changes consistent with morphea. He subsequently developed simple partial seizures involving left arm/leg shaking. Serial MRIs revealed progressive right cerebral/cerebellar and left occipital atrophy, all without contrast enhancement (figure 1B). T2 hyperintensities within the right cerebral white matter were noted (figure 1C). Biopsy of an area of such hyperintensity revealed perivascular lymphocytic T cell infiltrates with marked rarefaction and gliosis (figure 1D). There were increased CD3 and CD45 cells, further indicating T cell …

Periictal cerebral tissue hypoxemia: A potential marker of SUDEP risk

Cerebral oximetry has not been explored in patients experiencing seizures in the epilepsy monitoring unit (EMU). The purpose of our study was to evaluate the feasibility of periictal measurement of cerebral oxygenation using noninvasive cerebral tissue oximetry and to determine whether there was evidence of cerebral hypoxemia during generalized seizures. Cerebral oxygen saturation findings were subsequently correlated with sudden unexpected death in epilepsy (SUDEP) risk factors. We prospectively evaluated six patients admitted to our EMU with histories of generalized tonic–clonic seizures (GTCS) with prolonged scalp electroencephalography (EEG) and two regional cerebral oxygen saturation (rSO2) sensors. Minimum rSO2 values were recorded in the 5 min preceding seizure onset, during the seizure, and in the 5 min following seizure offset. SUDEP risk was assessed using the SUDEP‐7 Inventory. Cerebral oximetry was well tolerated, with a mean duration of rSO2 monitoring of 81.1 h. Cerebral oxygen saturation data were available from at least one sensor in 9 (90%) of 10 seizures; only 6 (60%) of 10 seizures had useable periictal digital pulse oximetry data. GTCS were associated with significantly lower minimum ictal (p = 0.003) and postictal (p = 0.004) %rSO2 values than the minimum preictal value. Patients with at least one seizure with a %rSO2 decrease of ≥20% tended to have higher SUDEP‐7 Inventory scores (mean SUDEP‐7 Inventory score 7 ± 2.8) versus patients without recorded desaturations (4.3 ± 0.5, p = 0.08). Larger studies are needed to determine the value of cerebral oximetry in the identification of patients at risk of SUDEP.