Faculty Bibliography

PURPOSE/OBJECTIVE:While seizure onset patterns have been the subject of many reports, there have been few studies of seizure termination. In this study we report the incidence of synchronous and asynchronous termination patterns of partial seizures recorded with intracranial arrays. METHODS:Data were collected from patients with intractable complex partial seizures undergoing presurgical evaluations with intracranial electrodes. Patients with seizures originating from mesial temporal and neocortical regions were grouped into three groups based on patterns of seizure termination: synchronous only (So), asynchronous only (Ao), or mixed (S/A, with both synchronous and asynchronous termination patterns). RESULTS:88% of the patients in the MT group had seizures with a synchronous pattern of termination exclusively (38%) or mixed (50%). 82% of the NC group had seizures with synchronous pattern of termination exclusively (52%) or mixed (30%). In the NC group, there was a significant difference of the range of seizure durations between So and Ao groups, with Ao exhibiting higher variability. Seizures with synchronous termination had low variability in both groups. CONCLUSIONS:Synchronous seizure termination is a common pattern for complex partials seizures of both mesial temporal or neocortical onset. This may reflect stereotyped network behavior or dynamics at the seizure focus.

Synesthesia is experienced when sensory stimulation of one sensory modality (the inducer) elicits an involuntary or automatic sensation in another sensory modality or different aspect of the same sensory modality (the concurrent). Auditory synesthesias (AS) occur when auditory stimuli trigger a variety of concurrents, or when non-auditory sensory stimulations trigger auditory synesthetic perception. The AS are divided into three types: developmental, acquired, and induced. Developmental AS are not a neurologic disorder but a different way of experiencing one's environment. They are involuntary and highly consistent experiences throughout one's life. Acquired AS have been reported in association with neurologic diseases that cause deafferentation of anterior optic pathways, with pathologic lesions affecting the central nervous system (CNS) outside of the optic pathways, as well as non-lesional cases associated with migraine, and epilepsy. It also has been reported with mood disorders as well as a single idiopathic case. Induced AS has been reported in experimental and postsurgical blindfolding, as well as intake of hallucinogenics or psychedelics. In this chapter the three different types of synesthesia, their characteristics, and phenomologic differences, as well as their possible neural mechanisms are discussed.

Refractory status epilepticus is a disease associated with high morbidity and mortality, which does not always respond to standard treatments, and when they fail, alternative modalities become crucial. Therapeutic hypothermia slows nerve conduction in vitro, and has been shown to abort seizures in animal models. Therapeutic hypothermia has been experimentally used in humans since 1963 for a variety of intracranial pathologies. More recently there have been multiple reports demonstrating the effectiveness of therapeutic hypothermia in treating refractory status epilepticus. We report a case of super-refractory status epilepticus successfully treated with therapeutic hypothermia, complimented by a historical and literature review of this modality. While there is limited evidence, and some risks associated with therapeutic hypothermia, it should be considered as a reasonable and potentially effective treatment option for refractory status epilepticus.

Zonisamide is an antiepileptic drug that is structurally different from other antiepileptic agents. Its long half-life, once-daily dosing, lack of induction of hepatic enzymes, and broad spectrum of action makes it a suitable candidate for monotherapy. It has been approved as monotherapy for partial onset epilepsy in Japan and South Korea for more than a decade, and was recently approved as monotherapy in Europe. In the USA, it is only approved by the US Food and Drug Administration for adjunctive treatment of partial onset epilepsy. In this paper, we briefly review the literature on zonisamide monotherapy in partial onset epilepsy with regard to its efficacy, safety, tolerability, and long-term side effects, including a recent noninferiority trial in comparison with extended-release carbamazepine. While European regulatory agencies use noninferiority trials for approval of monotherapy, such a trial design does not meet the current regulatory requirements for approval as monotherapy in the USA.

Juvenile myoclonic epilepsy is the most common form of idiopathic generalized epilepsy with onset at puberty or late teenage years. About 80-90% of patients with juvenile myoclonic epilepsy respond to appropriate antiepileptic treatment and achieve seizure freedom, and about 15% of patients become intractable. Valproic acid, levetiracetam, lamotrigine, topiramate and zonisamide are used as first line or adjunctive therapy of this disorder. Lacosamide is approved for adjunctive treatment of partial onset epilepsies. The role of lacosamide in treatment of idiopathic generalized epilepsy including juvenile myoclonic epilepsy is unknown. We present three patients with classic clinical and electrographic features of juvenile myoclonic epilepsy that were maintained on lacosamide (one on monotherapy and two as adjuvant therapy). There were no special pharmacodynamic actions causing exacerbation or worsening of myoclonic jerks or generalized seizures in these three patients. In conclusion, although, the data from our three patients' suggest that lacosamide may be effective in the treatment of juvenile myoclonic epilepsy, larger studies are needed to explore efficacy and role of lacosamide in the treatment of this disorder.

We present a case of acquired auditory-visual synesthesia and its neurophysiological investigation in a healthy 42-year-old woman. She started experiencing persistent positive and intermittent negative visual phenomena at age 37 followed by auditory-visual synesthesia. Her neurophysiological investigation included video-EEG, fMRI, and MEG. Auditory stimuli (700 Hz, 50 ms duration, 0.5 s ISI) were presented binaurally at 60 db above the hearing threshold in a dark room. The patient had bilateral symmetrical auditory-evoked neuromagnetic responses followed by an occipital-evoked field 16.3 ms later. The activation of occipital cortex following auditory stimuli may represent recruitment of existing cross-modal sensory pathways.

Holoprosencephaly is a category of congenital brain malformation that is frequently associated with epilepsy. Epileptic spasms and partial seizures are reported with a variety of electrographic ictal and interictal EEG findings. We report a case of severe alobar holoprosencephaly with cortical tissue limited to inferior-anterior-frontal areas and a thin mantle over the posterior areas, and no appreciable connective fibers to the subcortical structures. Interictal EEG consisted mainly of 2-3 Hz irregular delta activity during wakefulness and sleep. Clinical seizures had two different semiologies: (1) epileptic spasms lasting 0.5s during state change and (2) prolonged tonic spasms lasting 5-8s followed by appendicular clonic activity, abnormal nystagmoid eye movements and eye flutter lasting 5-8s. Preceding the epileptic spasms, there was 1-2s of electrodecrement in the EEG. During prolonged tonic spasms there was also electrodecrement in the EEG. No other electrographic activity was seen. Due to lack of any appreciable connecting fibers between cortical and subcortical structures, these findings suggest an increase in brain stem excitability with inefficient (or lack of) cortical modulation as a possible underlying mechanism for epileptic spasms in this patient.