Sleep Disorders in Patients With Craniopharyngioma: A Physiopathological and Practical Update

Abstract

Sleep disorders (SDs) represent an important issue in patients with craniopharyngioma (CP). Nearly 70% of these patients complain of sleep-wake cycle alterations and/or excessive diurnal somnolence due to sleep-related breathing disorders, such as obstructive sleep apnea (OSA) and/or central hypersomnia, including secondary narcolepsy. SDs may severely reduce quality of life, increase disease-related cardiorespiratory and cardiovascular morbidity, and finally play a major role in increased long-term mortality reported on patients with CP. A major risk factor for SDs is represented by the hypothalamic syndrome, which may develop because of direct hypothalamic damage by the tumor itself and/or complications of the treatments, neurosurgery and/or radiotherapy, and typically includes permanent neuroendocrine dysfunctions, morbid obesity, and secondary metabolic disorders. Despite increasing attention to SDs in the general population, and in particular to OSA as a risk factor for cardio-metabolic diseases and excessive daytime somnolence, sleep evaluation is still not routinely proposed to patients with CP. Hence, SDs are often underdiagnosed and undertreated. The aim of this paper is to update current knowledge of the pathogenesis and prevalence of SDs in patients with CP and propose practical algorithms for their evaluation and management in clinical practice. Particular attention is paid to screening and diagnostic tools for appropriate characterization of SDs, identification of risk factors, and potential role of hypothalamic sparing surgery in the prevention of morbid obesity and SDs. Available tools in sleep medicine, including lifestyle interventions, drugs, and respiratory devices, are discussed, as well as the importance of optimal hormone replacement and metabolic interventions. Current limits in the diagnosis and treatment of SDs in patients with CP and possible future avenues for research agenda are also considered.

Keywords: circadian rythm disorders; craniopharyngioma; hypersomnia; hypothalamic obesity; hypothalamic syndrome; narcolepsy; obstructive sleep apnea; sleep disorder.

Figure 1

Algorithm for the screening and identification of sleep disorders in patients with craniopharyngiomas. ICSD-3, International classification of sleep disorders version 3; CP, craniopharyngioma; SDs, sleep disorders; OSAS, obstructive sleep apnea syndrome; HSAT, home sleep apnea test; PSG, polysomnography; MSLT, multiple sleep latency test; CRSWD, circadian rhythm sleep-wake disorders. Endocrinologists and neurosurgeons should be involved in the screening step. The second step should be performed by a sleep specialist. ^aDiaries can help to obtain clinical points in a standardized manner. *The use of formal screening questionnaires for sleep disorders is advisable [i.e., STOP BANG for sleep apnea, Pittsburgh Sleep Questionnaire Index (PSQI) for SDs, Epworth Sleepiness Scale for EDS, Morningness-Eveningness Questionnaire to identify chronotype]. ^bSDs should be managed as per overall guidelines. ^cThe effects of treatments should be regularly evaluated [adherence to PAP, EDS by ESS score or Maintenance Wakefulness Test (MWT) together with multidisciplinary evaluation of obesity and related cardiometabolic complications as well as appropriate hormone replacement, where present. In particular, body mass index (BMI) should be noticed at each visit].

Figure 2

Algorithm for the management of sleep disorders in patients with CP. PSG, polysomnography; OSAS, Obstructive Sleep Apnea (OSA) syndrome; HSAT, home sleep apnea test; AHI, apnea-hypopnea index per hour of sleep; MSLT, multiple sleep latency test; MSL, mean sleep latency; ^aThe management of OSA should include weight loss, avoidance of alcoholic intake and smoking, sleep hygiene, and positional therapy. Positive Airway Pressure (PAP) is considered first-line treatment. Oral appliances may be suggested for mild to moderate OSA and surgery to correct anatomic obstructions (66). ^bThe treatment of central hypersomnias and secondary narcolepsy should include cognitive behavioral therapy (CBT) and approved stimulants (i.e., modafinil, pitolisant, solriamfetol, and sodium oxybate) (67). ^cSleep hygiene, CBT, and short-term pharmacologic approach should be considered for insomnia and CRSWD (68).

Figure 3

A 5-min segment from home sleep apnea test (HSAT) in the diagnosis of sleep-related breath disorders in a 51-year old male patient with CP. The patient was operated on for a huge supra- and retrosellar craniopharyngioma with hydrocephalus and ataxia, achieving complete resection of an adamantinomatous lesion. He developed post-operative diabetes insipidus and partial hypopituitarism, and had severe weight gain (+50 kg) with snoring and markedly excessive daytime somnolence (EDS), confirmed by a high ESS score (16/24). HSAT confirmed the presence of severe OSA syndrome (AHI 58.8/h), characterized by several obstructive apneas. PAP treatment induced the disappearance of EDS (ESS score 7/24). Overall, the patient was very compliant to lifestyle interventions and endocrinological management, and significant weight loss (−30 kg) was also achieved.

Figure 4

Examples of MSLT in the diagnosis of central hypersomnias in two female patients with CP. Patient 1 (A–D). Pre-operative evaluation of a 44-year-old woman who presented with spontaneous hypothalamic syndrome with severe weight gain (+30 kg) associated with headache, secondary amenorrhea, asthenia, insomnia, and diurnal somnolence. Contrast-enhanced T1-weighted magnetic resonance imaging (MRI) revealed a huge solid and cystic suprasellar lesion [(A), coronal view] with posterior extension [(B), sagittal view]. MSLT showed a 30-s epoch of NREM sleep (N2) (C) with hypnogram confirming severe excessive daytime somnolence (mean sleep latency 4.2 min) without sleep-onset REM in 5 of 5 nap periods (D). A diagnosis of central hypersomnia was made. Patient 2 (E–H). Post-operative evaluation of a 52-year-old woman affected by complex post-operative sleep disorders accompanied by diabetes insipidus, pan-hypopituitarism, ongoing severe weight gain (+7 kg before surgery, +30 kg after surgery) and asthenia. Preoperative contrast-enhanced T1-weighted MRI showed a huge solid and cystic suprasellar lesion [(E), coronal view] with posterior extension [(F), sagittal view]. Excessive daytime somnolence persisted on continuous PAP for documented post-operative OSA (data not shown), and MSLT was recently proposed. The MSLT showed a 30-s epoch of REM sleep (G), with hypnogram confirming severe excessive daytime somnolence (mean sleep latency 2.3 min) with sleep-onset REM in 2 of 5 nap periods [(H), see blue arrows]. A diagnosis of secondary narcolepsy was made, and a stimulant oral agent (modafinil) was started. In both patients, complete tumor resection was achieved, and pathological examination revealed adamantinomatous (patient 1) and papillary (patient 2) craniopharyngiomas. ROC, right oculogram; LOC, left oculogram; M1 and M2 reference electrodes placed on the mastoid process; Chin, Chin electromyogram.

Figure 5

Example of circadian sleep-wake alteration evaluation by actigraphy. A 75-year-old female patient came to our observation because of headache and visual loss in the context of recent and rapidly worsening neurological symptoms consisting of insomnia, excessive daytime somnolence, cognitive impairment, reduced appetite, and weight loss. No poliurodyspia was present, and basal pituitary function and electrolytes were normal. Contrast-enhanced T1-weighted MRI revealed a mixed cystic and solid tumor consistent with suprasellar craniopharyngioma (A) with retrosellar extension (B). Sleep-wake patterns are displayed for individual days on actigraphy (C): vertical black bars and the red line under each day indicate movement, and the absence of black bars indicates supposed sleeping periods. The blue band designates the sleep period. The actigram shows frequent nighttime activity, severe insomnia, sleep fragmentation, and frequent short diurnal naps. The patient is currently awaiting surgery.