Aside from repeated drug overdose, recurring episodes of stupor are usually a result of the recurrence of an underlying endogenous biochemical derangement such as the hyperammonemia of hepatic failure. A similar periodic hyperammonemic coma in children and adults can come about from urea cycle enzyme defects, such as ornithine transcarbamylase deficiency. These are discussed in Chap. 36.
Under the title of idiopathic recurring stupor, a rare condition has been described in adult men who displayed a prolonged state of deep sleepiness lasting from hours to days intermittently over a period of many years. Despite the impression of a sleep disorder related to narcolepsy, the EEG showed widespread fast (beta) activity, and both the stupor and EEG changes were reversed by flumazenil, a benzodiazepine receptor antagonist. During the bouts, a many-fold increase of circulating endozepine-4, an ostensibly naturally occurring diazepine agonist, was present in the serum and spinal fluid. Subsequently, the authors of the original reports (Lugaresi et al) found, by the use of more advanced techniques, that intoxication with lorazepam may have accounted for at least some of the cases. Although such cases in which diazepine antagonists reverse episodes of recurrent coma continue to be reported (Huberfeld et al), the status of this entity remains ambiguous because of the difficulty in excluding exogenous ingestion of drugs. The vigilance-producing drug, modafinil, has also been effective in one report (Scott and Ahmed).
A peculiar form of transient unresponsiveness in elderly individuals has been pointed out by Haimovic and Beresford. It accounted for 2 percent of hospitalized patients referred to them for coma. The EEG and other evaluations gave no explanation but their 5 patients had various systemic illnesses. It may recur but appears to be benign. We have experience with three such patients over the years, all men in their seventh or eighth decades, who had no systemic illness and who showed no Babinski signs, pupillary abnormalities and, for the most part, eye movement limitations (one had disproportionately better horizontal than vertical gaze with oculocephalic testing). Their eyes were closed and they could be aroused briefly and inconsistently to a drowsy state. EEG showed mild diffuse slowing but without organized sleep-like activity. Patients with advanced Parkinson disease will occasionally display a similar episodic unresponsiveness but with eyes open.
It is unclear to us whether migraine can cause a similar syndrome of unresponsiveness, as suggested in the study of familial hemiplegic migraine by Fitzsimmons and Wolfenden. Basilar migraine may exceptionally cause transient stupor and coma. Catatonic stupor and Kleine-Levin syndrome of periodic hypersomnolence (Chap. 18) and the behavioral change of catatonia also need to be considered.
Coma is produced by one of two broad types of processes: The first is clearly structural, or morphologic, consisting either of a discrete structural lesion in the upper brainstem and lower diencephalon (which may be primary or secondary to compression) or of more widespread destructive changes throughout the hemispheres. The second type is metabolic or submicroscopic of the type discussed above under the topic or metabolic encephalopathy, resulting in suppression of neuronal activity in the cerebrum and reticular activating system. The clinical examination in coma is designed to separate these mechanisms and to gauge the depth or seriousness of underlying dysfunction.