Obstructive Sleep Apnea Syndrome: A Cause of Acute Delirium

Abstract

Delirium is a transient global disorder of cognition related to a variety of structural or functional neural disorders. Descriptions and characterizations of delirium associated with obstructive sleep apnea syndrome (OSAS) are rare. We describe a 52-year-old man with severe OSAS associated with sudden onset of delirium and with a fluctuating nighttime course, prolonged for several days. The delirium disappeared after treatment with continuous positive airway pressure (CPAP). The patient remained free of symptoms under CPAP during a follow-up of 8 years.

Citation:

Lombardi C; Rocchi R; Montagna P; Silani V; Parati G. Obstructive sleep apnea syndrome: a cause of acute delirium. J Clin Sleep Med 2009;5(6):569-570.

The term delirium comes from the Latin and means “off the track.” It was mainly employed to describe the syndrome of alcohol withdrawal, i.e. delirium tremens. Delirium, also known as acute confusional state, is a transient global disorder of cognition. The clinical hallmarks consist of a decreased attention span combined with a waxing and waning mental confusion, and acute or subacute deterioration of behavior and cognitive functions associated with visual hallucinations or persecutory delusions.

The pathophysiological mechanisms of delirium are still not fully understood. A variety of structural or functional neural disorders may result in delirium. The pathogenesis of its neural manifestations has been relatively well studied in patients with hepatic encephalopathy and alcohol withdrawal, but research in other areas is still limited. In particular, the occurrence of delirium in association with OSAS has rarely been described.^1–4

We report here the case of an OSAS patient showing a sudden onset of delirium with a fluctuating nighttime course, persisting over several days, which disappeared after treatment with CPAP. The patient was examined in the acute phase and followed-up for 8 years.

REPORT OF CASE

A 52-year-old man was admitted in November 2000 to the Sleep Disorders Center of the Policlinico Le Scotte, Siena, because of a confusional state of abrupt onset. According to his wife, during sleep the patient presented an episode of sudden awakening with agitation, aggressive and disorganized behavior and clouding of consciousness with coenesthesic hallucinations (the patient reported the sensation of being born at that time and he felt small animals moving on his body). During this episode, the patient, completely naked, opened a window and tried to jump out. On admission, he displayed a behavior characterized by agitation, poor time and space orientation, with fluctuations in alertness.

One year before, a condition of OSAS had been diagnosed, but the patient refused to undergo any treatment. In the 2–3 months before admission he had gained 5–6 kg body weight and was reported to snore heavily with frequent apneas and severe daytime sleepiness. There was no personal or family history of mental illness and no history of drug abuse. Neurological and physical examinations were normal at admission, except for marked obesity with a body mass index (BMI) of 34 kg/m². Full blood count, liver function tests, serum urea and electrolytes, blood sugar, Free Triiodothyronine (FT3), Free Thyroxine (FT4), Thyroid-stimulating hormone (TSH), immunological screening tests, serum osmolality, folate and vitamin B12 were all normal. Urine screening was negative for ethanol, barbiturates, benzodiazepines, cannabinoids, and narcotics. Repeated body temperature examinations, chest radiograph, electrocardiogram, spirometry and daytime arterial blood gas analysis all yielded normal results. A daytime EEG showed a slow background activity but no evidence of focal abnormalities. However, no sign of cognitive impairment was evident at neuropsychological testing. Brain Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) were normal.

Because of the previous diagnosis of OSAS, the patient was placed on nocturnal CPAP therapy (air pressure = 10 cm H₂O) which led to complete disappearance of his symptoms after 3 days. A video polysomnography performed without CPAP 15 days after remission of the symptoms showed a severe OSAS, with an apnea hypopnea index (AHI) of 45 and a minimum oxygen saturation of 59%. No polysomnographic markers (alterations of physiologic muscle chin atonia) of REM behavior disorder (RBD) were found during REM sleep, although bursts of EMG activity on myloioideus muscle were detectable without clear behavioral manifestations.

No recurrence of delirium or development of dementia has been observed over 8 years of follow-up with the patient under regular CPAP therapy.

DISCUSSION

Our patient showed abrupt nocturnal onset of clinical manifestations, fulfilling the DSM-IV diagnostic criteria for delirium,⁵ after an important body weight gain associated with increased snoring and sleep apneas. Delirium completely disappeared after nocturnal CPAP use, and the patient remains symptom-free after 8 years of CPAP therapy.

Given the clinical history, we consider the patient's delirium as depending on the effects of sleep-disordered breathing.^1–4 The causative mechanisms are however unclear, though a number of pathogenic factors could have been implicated.

A first possibility is that delirium might be due to a “respiratory encephalopathy.” In fact, the effects of inadequate brain oxygen supply on cognitive and sensorimotor performances are well documented. Intermittent hypoxia induces oxidative stress, apoptosis, and specific changes particularly in the protein profile of the hippocampal CA1 area and in the prefrontal cortex.⁶ However, the prevalent nocturnal occurrence of symptoms and the absence of alterations in either daytime ventilation or arterial gas content (i.e., hypoxia and/or hypercapnia) argue against such interpretation. Another possibility is that sleep disordered breathing might determine neurotransmitter abnormalities that could be related to chronic sleep deprivation,⁷ particularly to REM sleep deprivation.

OSAS is indeed an important determinant of sleep fragmentation, REM and NREM deep sleep deprivation, hormonal circadian rhythm alterations and cognitive impairment. Sleep mechanisms may also play a role in the generation of visual hallucinations, such as with the hypnagogic hallucinations of narcolepsy, thought to derive from a REM-dissociation state, and the visual hallucinations in Parkinson disease.⁸ Moreover acute delirium with coenesthesic hallucinations have also been described in a patient with restless legs syndrome and pneumonia.

In this regard, it is of great interest that OSAS, known as a potential precipitating factor for episodes of RBD in patients prone to this disorder, may be sometime associated with a more complex form of status dissociatus, a dissociation of the determinants of the states of being that may result in an abnormal behavior and altered cognition.^9,10

The prevalent nocturnal occurrence of the confusional state and of the behavioral abnormalities in our patient is indeed well in accordance with an “acute and transient” status dissociatus developing in the setting of chronic sleep deprivation in a patient with severe OSAS. The predominant role of sleep deprivation is suggested by the observation that the patient did not show any polysomnographic characteristic feature of RBD a few days following the acute event.

Whatever the pathogenic mechanisms implicated, OSAS must be considered in the differential diagnosis of the mechanisms responsible for delirium. This indication is of clinical relevance mainly because whenever OSAS is the responsible mechanism for delirium, this condition can be cured, as OSAS is reversible with adequate treatment.

DISCLOSURE STATEMENT

This was not an industry supported study. The authors have indicated no financial conflicts of interest.