Epilepsy spectrum disorders

Boutros NN, Bowyer S, Wang J, Urfy MZ, Loeb JA. Epilepsy spectrum disorders: A concept in need of validation or refutation. Med Hypotheses. 2015 Aug 18. pii:S0306-9877(15)00309-6. doi: 10.1016/j.mehy.2015.08.004. [Epub ahead of print]

Abstract

Episodic psychiatric symptoms are not uncommon and range from panic attacks to repeated violent acts. Some evidence has accumulated over the years that at least in a subset of patients exhibiting these symptoms there may be evidence for the presence of focal cortical/subcortical hyperexcitability. In these cases the condition could be conceptualized as an epilepsy spectrum disorder (ESD) with significant treatment implications. There is currently no clear demarcation of this category of symptoms, their prevalence, an understanding of how these symptoms occur, what is appropriate work up and possible treatments. In this article, we propose that milder degrees of increased neural excitability (i.e., a subthreshold excitation insufficient to cause seizures) may nonetheless be capable of causing observable phenotypic changes. The observable phenotypic changes depend on the degree of hyperexcitability and the location of the hyperexcitable neural tissue. The location of the abnormal neural tissue may dictate the initial manifestation of an attack resulting from activation of the hyperexcitable tissue, but the anatomical connectivity of the abnormal region will dictate the breadth of manifestations. We provide some evidence, derived mainly from either electroencephalography studies of these populations or clinical reports of response to anti-epilepsy treatment, for the assumption and propose methods to test the advanced hypothesis.

From the paper:

For decades, psychiatrists harbored a vague notion simmering just below the level of verification that paroxysmal EEG discharges without overt, conventionally defined seizures (i.e., isolated epileptiform discharges or IEDs) may have behavioral consequences such as emotional lability, irritability, or temper dyscontrol. Previous conceptualizations and terms used to describe individuals with these symptoms include: Subictal Neurosis, Episodic Dyscontol, variants of complex partial seizures, sub-clinical seizures and post-traumatic temporal lobe dysfunction , and atypical Psychosis . The term epilepsy spectrum disorders (ESD) was proposed by Springer and colleague and was subsequently used by Roberts et al. This term generated significant controversy and was all but abandoned. The term “multiple-partial seizure-like symptoms without stereotyped spells” was proposed more or less to avoid the controversy, while emphasizing the fact that such groups of patients are commonly encountered in psychiatric clinics.
 

Available literature suggests that any episodic behavior could potentially be ESD. This would include disorders like atypical Panic Disorder (PD), repeated (particularly seemingly unmotivated) aggression, autism spectrum disorders, as well as some forms of rapid cycling mood disorders. A number of single case reports also suggested that some cases of borderline personality disorder may in fact be ESD…It is presumed that this hyperexcitable tissue is the core problem in epilepsy. It is, of course, a well-known observation that seizures are episodic whereas tissue abnormalities are likely to be permanent. Thus, it must be postulated that other factors; biological and/or environmental, play a role in determining when actual seizures occur…

We propose that milder degrees of increased neural excitability (i.e., a subthreshold excitation insufficient to cause seizures) may nonetheless be capable of causing observable phenotypic changes. The observable phenotypic changes (in this paper we focus mainly on observable behavioral changes) depend on the degree of hyperexcitability and the location of the hyperexcitable neural tissue. The location of the abnormal neural tissue may dictate the initial manifestation of an attack resulting from activation of the hyperexcitable tissue, but the anatomical connectivity of the abnormal region will dictate the breadth of manifestations…

Conclusions

We propose that a thorough work-up (along the lines outlined above) could be useful in guiding the treatment of individual patients suspected of having an ESD. An abnormal EEG/MEG exhibiting paroxysmal activity, particularly if emanating from the fronto-temporal limbic regions, may be indicative of a higher likelihood of a positive response to an AED. We further suggest that when the EEG/MEG exhibit a focal abnormality that an AED of the carbamazepine family of drugs be utilized first. Finally, we also predict that when a possible ESD patient with a normal EEG/MEG scores high on the SCIPS for the EEG/MEG to be repeated following a full night of sleep deprivation and with a 5 min of vigorous hyperventilation. Longer term Video-EEG monitoring in an epilepsy monitoring unit could provide important clues particularly if recording can be obtained during an actual episode.

Although there are various ways to document a hypothesis or produce validity for new diagnosis, an often neglected concept is that of “treatment validity”. In this regards, it seems likely that the concept of ESD will not be fully accepted by most neuropsychiatrists until at least one double-blind, randomized controlled medication study demonstrates that medications such as valproic acid, carbamazepine/oxcarbazepine, lamotrigine or tiagabine produce major clinical improvement in objectively defined samples of patients who endorse multiple episodic symptoms that are refractory to conventional psychopharmacology.

A final thought is regarding the label “Epilepsy Spectrum Disorders”. As has been discussed above, this term may in fact lead to confusion between epilepsy, epilepsy equivalents (which are epileptic in nature), and epilepsy spectrum disorders (which are not epileptic in nature) [76] . Hence it may be better to propose a term that avoids the word “epilepsy” like for example “focal hyperexcitability disorders or FHS).

 

 

 

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