NREM sleep stage transitions control ultradian REM sleep rhythm.

STUDY OBJECTIVES: The cyclic sequence of NREM and REM sleep, the so-called ultradian rhythm, is a highly characteristic feature of sleep. However, the mechanisms responsible for the ultradian REM sleep rhythm, particularly in humans, have not to date been fully elucidated. We hypothesize that a stage transition mechanism is involved in the determination of the ultradian REM sleep rhythm. PARTICIPANTS: Ten healthy young male volunteers (AGE: 22 ± 4 years, range 19-31 years) spent 3 nights in a sleep laboratory. The first was the adaptation night, and the second was the baseline night. On the third night, the subjects received risperidone (1 mg tablet), a central serotonergic and dopaminergic antagonist, 30 min before the polysomnography recording. MEASUREMENTS AND RESULTS: We measured and investigated transition probabilities between waking, REM, and NREM sleep stages (N1, N2, and N3) within the REM-onset intervals, defined as the intervals between the onset of one REM period and the beginning of the next, altered by risperidone. We also calculated the transition intensity (i.e., instantaneous transition rate) and examined the temporal pattern of transitions within the altered REM-onset intervals. We found that when the REM-onset interval was prolonged by risperidone, the probability of transitions from N2 to N3 was significantly increased within the same prolonged interval, with a significant delay and/or recurrences of the peak intensity of transitions from N2 to N3. CONCLUSIONS: These results suggest that the mechanism governing NREM sleep stage transitions (from light to deep sleep) plays an important role in determining ultradian REM sleep rhythms.

Two cases of neuroleptic-induced prolonged extrapyramidal symptoms.

Neuroleptic-induced extrapyramidal symptoms (EPS) are generally categorized as acute, withdrawal and tardive EPS. Here, we report two cases of a unique late-onset, long-lasting EPS (e.g., prolonged EPS); in those cases, EPS appeared a few months following initiation of haloperidol and lasted for a few months after significant reduction or complete withdrawal of neuroleptics. Case 1, a 41-year-old female, began to exhibit EPS such as bradykinesia, rigidity and parkinsonian gait 4 months after the haloperidol treatment. Her rigidity was ameliorated by a reduction of haloperidol; however, reduction of neuroleptics made it difficult for her to maintain a seated posture because of an imbalance of muscle tonus. Her EPS continued for 9 months even after haloperidol was switched to very low doses of thioridazine (10 mg/day). Case 2 is a 42-year-old female. She exhibited EPS including dysphagia and a difficulty in opening her mouth 3 months after the haloperidol treatment began. Her EPS lasted for 45 days, even after complete withdrawal of neuroleptics. The EPS observed in these two cases occurred even after prolactin levels became normal. "Prolonged EPS" is a unique subclass of neuroleptic-induced reversible EPS that might involve the coexistence of hypo- and hyper-dopaminergic transmission, especially in patients who show very low tolerance to neuroleptics.