A group of Chinese researchers and clinicians have reported that "interictal centrotemporal spikes" can disrupt brain networks responsible for language, behavior, and cognition, and that suppressing such discharges can reduce the risk of neuropsychological impairments in children.1 This study adds to the growing body of evidence that "spikes" are associated with impairment of brain function, and their negative consequences can be reversed by spike suppression. These findings are similar to what CNNH clinicians reported in 2009.2
"Spikes" are electrical discharges that can be detected by electroencephalography (EEG). When an individual with epilepsy has a seizure while connected to an EEG device, spike discharges are often seen, and thus, the term "epileptiform discharges". However, spikes can also be observed when an individual is not having a clinically observable seizure event and are labeled "interictal epileptiform discharges" (IED) or "subclinical spikes" (SCS). For many years SCS were interpreted as "benign" and not meriting further concern or intervention, especially a certain subtype of SCS called a "rolandic spike" (RS). However, many clinicians and researchers have long questioned this conventional wisdom. SCS/IED can be found in individuals carrying epilepsy diagnoses (epilepsy is defined by clinically observable convulsions or other seizure events), but as our group at CNNH has reported utilizing high-density EEG (HD-EEG) technology, SCS can also be found "unexpectedly" at relatively high rates in individuals not observed to have had a seizure event, including those with autism, ADHD/Learning Disorders, and various neurobehavioral, neuropsychiatric, and neurodevelopmental disorders.3
Why does this occur? In some cases clinical seizures may be too brief or subtle to observe. In other cases SCS may represent a predisposition for the eventual development of epilepsy. However, SCS can also be an electrophysiological expression for underlying brain abnormalities (structural, metabolic, inflammatory, neurotransmitter, etc.) or genetic variations that cause abnormalities in regulation of brain cell "ion channels" (the inward and outward flow of sodium, calcium, potassium, magnesium). Thus, seizures are just the "tip of the iceberg", and there should be consideration of an expanded concept of "epilepsy spectrum disorders": that is, there are sizable groups of individuals with electrical changes of the brain that have no clinically observable seizures, but who experience neuropsychological, neurobehavioral, or neuropsychiatric impairment or disturbances. These individuals may or may not go on to develop clinical seizures at some point, but select patients may benefit from treatments that are used for epilepsy. Likewise, there are many individuals with epilepsy who may or may not have SCS/IED, but who have neuropsychological and neurobehavioral deficits and disturbances.
What are the practical implications for patients? Identification of SCS may indicate neuropsychological deficits, "organic" behavioral abnormalities, metabolic disturbances, significant genetic variations, unrecognized epilepsy, or may forewarn about impending epilepsy. SCS associated with objective evidence of brain impairment or behavioral problems informs about potentially efficacious treatments targeting spike suppression, which may lead to functional improvements. For example, rather than getting a stimulant drug for "ADHD", the finding of SCS may enlighten about treatments with relatively well-tolerated medications such as levetiracetam and others, or may result in neurodiagnostic testing that identifies neuropsychological or learning impairments that can respond to non-pharmacological interventions. Thus, EEG, and in particular the patient-friendly technology HD-EEG with its ability to provide 3-D electrical source imaging (ESI) of neuronal (e.g. neurons are the primary brain cell) activity, should be part of the diagnostic and management approach for appropriately selected patients presenting with various types of neurological, neurobehavioral, neuropsychiatric, and neurodevelopmental disorders.
There are many types of ways to "image" the brain, such as magnetic resonance imaging (MRI) that provides a "structural", static image of the brain; functional MRI (fMRI), which relies on blood flow as an indirect measure of brain activity; MR spectroscopy (MRS) that measures metabolic activity; and others. Yet, ESI remains the only real-time, non-invasive tool that directly measures neuronal/brain activity, and can be performed in a comfortable office setting without sedation or restraint.4
We have entered an age where "psychiatric" disorders are increasingly recognized as having a neurological basis, and many neurological syndromes have psychiatric manifestations. Thus, the divide or differentiation between "psychiatric" and "neurologic" is often artificial, as it is all truly "neurological, neurobiological, and neuropsychiatric". Therefore, "labeling" individuals with non-specific diagnoses such as ADHD, anxiety, learning disorder, autism, etc. without regard to their biological mechanisms is inadequate. Rather, we are now in an era where we can characterize a "biological phenotype" and "clinical profile" for these kinds of disorders by identifying abnormalities or disturbances in biological and behavioral functioning, allowing for treatments that target mechanisms of diseases and disorders rather than only suppressing symptoms, thereby improving outcomes and quality of life. This approach fulfills the aspirations of "personalized" and "precision" medicine.
1 Xiao, et al.Real-time effects of centrotemporal spikes on cognition in rolandic epilepsy: An EEG-fMRI study. Neurology 2016; 86:544-551.
2 Mintz, et al.:The under-recognized epilepsy spectrum: the effects of levetiracetam on neuropsychological functioning in relation to subclinical spike production. Journal of Child Neurology 2009; 24:807-15.
3 Mintz, et al.: Unexpected subclinical spikes: clinical and neurophysiological correlations. Abstract No. 2.016, 2014, American Epilepsy Society Annual Meeting, www.aesnet.org.
4 Szklarski and Mintz: Dense-array electroencephalography (dEEG) improves compliance and acquisition without sedation or restraint for children and adults with behavioral challenges. Abstract No. 3.133, 2015, American Epilepsy Society Annual Meeting, www.aesnet.org.
