When patients with Creutzfeldt-Jakob disease are misdiagnosed as having nonconvulsive status epilepticus.

Abstract

Contemporary studies report nonconvulsive status epilepticus (NCSE) in Creutzfeldt-Jakob disease (CJD), based on benzodiazepine (BZP)-responsive epileptiform discharges on the electroencephalogram (EEG), with the following false syllogism: (1) intravenous (IV) administration of BZPs usually suppress ictal activity in NCSE; (2) in CJD, periodic sharp wave complexes (PSWCs) are suppressed by IV BZPs; (3) therefore, these patients have NCSE. This is a simplistic and invalid conclusion, because authors of 20th-century science reports have clearly shown that IV BZPs, short-acting barbiturates, and drugs with no antiseizure effects, such as chloral hydrate and IV naloxone, suppress PSWCs, but patients fall asleep with no clinical improvement. In contrast, IV methylphenidate transiently improves both the EEG and clinical states. Unlike NCSE, which is unlikely to be stopped by external stimuli, PSWCs can be transiently stopped by sensory or painful stimulation. Since the end of the 1970s, the effect of spontaneous sleep on the disappearance of PSWCs has been well documented, with a description of a cycling alternating pattern. Phase A features periodic discharges and is associated with increased arousal, whereas phase B exhibits a reduction or suppression of the PSWCs and is associated with a reduction in the arousal level and hypotonia (non-rapid eye movement sleep). When considering the use of IV BZP administration during EEG as a diagnostic test, the sequence of disappearance of PSWCs at sleep onset and reappearance after each stimulation or sleep apnea episode is compelling evidence against NCSE, as is the observation of a pattern of stimulus-induced wakefulness with transient improvement of the EEG. The cycling alternating pattern during sleep and reactivity to sensory or painful stimulation disappear with increasing disease severity; however, this occurs in the later stages of the disease, where there is no diagnostic doubt.