Sleep stage sequence analysis of sleep onset REM periods in the hypersomnias.

BACKGROUND: The Multiple Sleep Latency Test (MSLT) remains an important diagnostic tool in the diagnosis of hypersomnias. However, a positive MSLT may be found in other sleep disorders, such as behaviourally induced inadequate sleep syndrome (BIISS). It has been demonstrated that in sleep onset rapid eye movement (SOREM) periods in BIISS, REM sleep tends to arise from stage 2 sleep (non-REM (NREM) 2), rather than stage 1 sleep (NREM1), as in narcolepsy. METHODS: We performed sleep stage sequence analysis on 127 patients with nocturnal polysomnography and MSLT, including 25 with narcolepsy with cataplexy (N+C), 41 with narcolepsy without cataplexy (N-C), 21 with idiopathic hypersomnia with long sleep time (IHL), 20 with BIISS and 20 with periodic limb movement disorder (PLMD). 537 naps were recorded, containing 176 SOREM periods. RESULTS: All SOREM periods in the IHL, BIISS and PLMD groups arose from NREM2 sleep, 75% of those in N+C arose from NREM1 and in N-C only 52% arose from NREM1. Within the N-C group, those with SOREM periods all arising from stage 1 had a shorter MSL (p=0.02). CONCLUSIONS: These results suggest that SOREM periods arising from NREM1 have high sensitivity for the diagnosis of narcolepsy and that SOREM periods from NREM1 are a marker of severity, either of sleepiness or REM instability. Sleep stage sequence analysis of SOREM periods may also aid more accurate phenotyping of the hypersomnias and in particular clarify heterogeneity among patients with narcolepsy without cataplexy.

Urine Toxicology in Adults Evaluated for a Central Hypersomnia and How the Results Modify the Physician's Diagnosis.

STUDY OBJECTIVES: Drugs and psychoactive substances can cause sleepiness and when undetected, may lead to over diagnosis of central hypersomnias. We performed urine drug testing using gas chromatography-mass spectrometry in adults undergoing multiple sleep latency testing (MSLT) for a suspected central hypersomnia. We examined how the drug test results modified the treating physician's diagnosis. METHODS: One hundred eighty-six consecutive patients with a suspected central hypersomnia who underwent clinical assessment, MSLT and urine drug testing by gas chromatography-mass spectrometry were retrospectively studied. Physicians made a diagnosis after clinical assessment and MSLT and were initially blinded to the urine drug test results. RESULTS: A third of patients assessed for subjective hypersomnia had a positive urine drug test for a substance affecting sleep. Opioids, cannabis, and amphetamines were the commonest drugs detected. Using MSLT, 35 (18.8%) of 186 patients had objective hypersomnia that may have been due to a drug or substance. Drugs or substances may have confounded the MSLT in 11 (20.1%) of 53 patients who fulfilled diagnostic criteria for idiopathic hypersomnia, and 12 (52%) of 23 of those who fulfilled diagnostic criteria for narcolepsy without cataplexy. Of the 75 positive urine drug samples, 61 (81%) were substances or medications not revealed in the physician interview. The treating physician had not suspected drugs or substances as a possible cause of objective hypersomnia in 34 (97%) of the 35 patients. CONCLUSIONS: Drugs and psychoactive substances can confound the results of the MSLT and when undetected could lead to over diagnosis of central hypersomnias.

First rapid eye movement sleep periods and sleep-onset rapid eye movement periods in sleep-stage sequencing of hypersomnias.

OBJECTIVES: Discrimination between narcolepsy, idiopathic hypersomnia, and behavior-induced inadequate sleep syndrome (BIISS) is based on clinical features and on specific nocturnal polysomnography (NPSG) and multiple sleep latency test (MSLT) results. However, previous studies have cast doubt on the specificity and sensitivity of these diagnostic tools. METHODS: Eleven variables of the NPSG were analyzed in 101 patients who were retrospectively diagnosed with narcolepsy with cataplexy (N+C) (n=24), narcolepsy without cataplexy (N-C) (n=38), idiopathic hypersomnia with long sleep period (IHL) (n=21), and BIISS (n=18). RESULTS: Fifteen out of 24 N+C and 8 out of 38 N-C entered the first rapid eye movement (REM) sleep period (FREMP) from sleep stage 1 (N1) or wake (W), though this sleep-stage sequence did not arise in the other patient groups. FREMP stage sequence was a function of REM sleep latency (REML) for both N+C and N-C groups. FREMP stage sequence was not associated with mean sleep latency (MSL) in N+C but was associated in N-C, which implies heterogeneity within the N-C group. REML also was a useful discriminator. Depending on the cutoff period, REML had a sensitivity and specificity of up to 85.5% and 97.4%, respectively. CONCLUSIONS: The FREMP stage sequence may be a useful tool in the diagnosis of narcolepsy, particularly in conjunction with sleep-stage sequence analysis of sleep-onset REM periods (SOREMPs) in the MSLT; it also may provide a helpful intermediate phenotype in the clarification of heterogeneity in the N-C diagnostic group. However, larger prospective studies are necessary to confirm these findings.

Diagnosis of PLMD from increased pulse rate variability on overnight oximetry.

STUDY OBJECTIVE: This study was undertaken in a group of patients with periodic limb movement disorder (PLMD) to assess whether the presence of increased pulse rate variability (PRV) without desaturation on overnight oximetry was suggestive of the occurrence of periodic limb movements (PLMs). METHODS: Seventy sleepy patients with a polysomnographic diagnosis of PLMD and 25 controls with obstructive sleep apnea were included in this retrospective study. All patients had undergone initial domiciliary oximetry and subsequent polysomnography (PSG). The oximetry tracings were independently interpreted by five sleep unit personnel for the presence of increased PRV. Further, the association between increased PRV and PLMs was evaluated in the summary graph of the PSG. RESULTS: Fifty seven (81.4%) patients had definite evidence of increased PRV without episodes of desaturation on initial oximetry, which was later confirmed to be due to PLMs on PSG. 13 (18.6%) patients had no PRV on oximetry and PSG but had PLMD. The inter-interpreter concurrence in suspecting a diagnosis of PLMD based on oximetry alone was more than 80% in 64 (91%) patients. CONCLUSION: The presence of isolated increased PRV on overnight oximetry is a valuable tool in suspecting nonsleep apnea disorders like PLMD.

Unusual case of subcutaneous panniculitis-like T-cell lymphoma.

An unusual case of subcutaneous panniculitis-like T-cell lymphoma is presented involving multiple organ systems, which eventually culminated in rapid demise from the haemophagocytic syndrome, after an initial protracted course. A 44-year-old man presented in April 2001 with bronchiolitis obliterans organising pneumonia that initially responded well to corticosteroids. However, the condition relapsed on attempted prednisone withdrawal in January 2002 and the patient was noted to have developed truncal subcutaneous nodules. Initial skin biopsy revealed lobular panniculitis, with negative microbiological culture. In July 2002, mononeuritis multiplex was diagnosed after the patient presented with paresthesiae and was treated with pulse cyclophosphamide therapy. By November 2002 there was ulceration of the subcutaneous nodules. Repeat skin biopsy revealed subcutaneous panniculitis-like T-cell lymphoma. The clinical manifestations were supportive of an unifying diagnosis of malignancy involving pulmonary, cutaneous and nervous systems. Combination chemotherapy with fludarabine, mitoxantrone and dexamethasone was commenced. However, the patient deteriorated, with fevers, weight loss, pancytopenia and laboratory features consistent with the haemophagocytic syndrome. Despite maximal supportive therapy the patient succumbed to his disease.