Sleep-potentiated epileptic discharges, language regression, and pediatric thalamic lesions Mark Quigg, MD, MS, FANA Soheyl Noachtar, MD Neurology ® 2012;78:1708–1709 Ever since Gloor et al. 1 demonstrated that thalamo- cortical interactions were responsible for generalized seizures, alterations of thalamic function have been investigated in the pathophysiology of epilepsy. To- day, the thalamus (in its regulatory, synchronizing actions with the cortex) has been assigned diverse roles. To name just two: 1) in potentiating seizure occurrence during sleep 2 ; and 2) in its electrical stim- ulation, treatment of seizures. 3 In addition, recent neuroimaging work has demonstrated heretofore poorly documented anatomic thalamic pathology in generalized epilepsy, 4 and perhaps not coinciden- tally, in autism. 5 In this issue of Neurology ® , Sa ´nchez Ferna ´ndez et al. 6 evaluated the neuroimaging of children who pre- sented with regression of at least 1 domain of devel- opment—typically language or behavior—who were suspected of having acquired epileptic aphasia. After dividing the sample into 2 arms, those whose electro- physiologic sleep was interrupted by long runs of ep- ileptiform discharges (electrical status epilepticus of sleep [ESES]) and controls of those without sleep- activated abnormalities, the authors report that ESES was more likely to be present in those with early developmental lesions that usually involved the thalamus. Regardless of exact cause (most commonly, early stroke), children with thalamic lesions had over 7 times the risk of ESES than children without. The findings of this report have 2 areas of importance. First, the Venn diagram of acquired epileptic aphasia (AEA) remains complicated. After all, Landau-Kleffner syndrome is a clinically defined syn- drome. The cardinal feature is acquired aphasia (most specifically auditory verbal agnosia) in which the majority of children have seizures. In Landau- Kleffner syndrome, the EEG is supportive in diagno- sis. 7 ESES, as first described by Patry et al. 8 and expanded by Tassinari et al. 9 and others, is electro- graphically defined, with non-REM sleep being sup- planted by ongoing epileptic discharges. Autistic spectrum disorders, especially in children who pres- ent with autistic regression or seizures, can be diffi- cult to distinguish on pure clinical grounds from more “traditional” AEA. 10 Although case reports of causes of AEA or ESES demonstrate a wide range of etiologies, the present article is the largest series to clearly link clinical suspicions of AEA with EEG and neuroimaging findings of early thalamic injury. Second, the finding of early thalamic injury asso- ciated with ESES is a robust clinical demonstration of the regulatory role of the thalamus as a source of synchronizing, oscillatory activity during non-REM sleep and the facilitation of seizure activity through abnormal cortico-thalamic synchronicity. 2 There is some evidence of a “dose-response” in that the pro- portion of patients with thalamic lesions increases with spike-wave persistence. Of major importance would be the other side, that behavioral and language outcomes may be proportional to the degree of sleep disruption by persistent spike-wave discharges. Such a finding is central to hypotheses of the role of sleep’s importance in memory function and a justification for aggressive antiepileptic treatment in ESES and AEA. Remaining uncertain is how to classify patients: AEA remains a collection of clinically related syn- dromes with no unitary “final common pathway” pathophysiology. For example, children with autistic traits—in addition to the index symptoms of behav- ioral or language decline— comprised about a third of the sample. These patients tended not to express sleep-potentiated epileptiform activity, despite hav- ing the primary inclusion criteria of behavioral or language decline. Perhaps future functional neuro- imaging studies, such as those that detailed changes in thalamic activity in autism, 11 can help bring to- gether clinical and electrophysiologic findings. Although it is probably too early to make changes in practice, the search for thalamic dysfunction may prove to be a helpful anatomic correlate to symptoms of language regression, behavioral changes, and epilepsy accompanied by sleep- potentiated EEG abnormalities. See page 1721 Correspondence & reprint requests to Dr. Quigg: quigg@virginia.edu From the Department of Neurology (M.Q.), University of Virginia, Charlottesville; and Department of Neurology (S.N.), University of Munich, Germany. Go to Neurology.org for full disclosures. Disclosures deemed relevant by the authors, if any, are provided at the end of this editorial. EDITORIAL 1708 Copyright © 2012 by AAN Enterprises, Inc.