The Diagnosis and Treatment of Sleep Disordered Breathing in a Hypermobile Population
Sleep Disordered Breathing (SDB) is common in patients with hypermobility syndromes including Hypermobile type Ehler-Danlos (hEDS) and generalized joint hypermobility syndrome. These syndromes are a connective tissue disorder characterized by the hyperflexibility of joints. SDB in these patients is thought to be caused by an abnormally flexible airway which collapses upon inspiration and produces Upper Airway Resistance Syndrome (UARS). Patients with hypermobility syndromes often have symptoms of dysautonomia including problems with blood pressure and heart rate regulation, abnormal reflexes, autoimmune disorders and reproductive problems including endometriosis and polycystic ovarian syndrome. They also frequently present with headache and fatigue.
Polysomnography is Crucial to the Diagnosis of Sleep Disordered Breathing inPatients with Hypermobility Syndromes
Patients with hypermobile Ehlers-Danlos syndrome, as well as Hypermobility Spectrum Disorder (HSD) have narrow, flexible airways, predisposing them to sleep disordered breathing (SDB). They do not typically present with the usual risk factors for SDB including obesity, male gender, and hypertensive disorder. Hypermobile patients frequently have a milder form of SDB that is not detected on a Home Sleep Test (HST), thus requiring the sensitivity of a Polysomnogram (PSG). HST’s provide a Respiratory Event Index (REI) which is used to diagnose Obstructive Sleep Apnea (OSA). In contrast, PSG’s provide multiple sleep indices including Apnea Hypopnea Index (AHI), Respiratory Effort Related Arousal Index (RERA Index), and the Arousal Index. Due to the increased sensitivity of PSG’s, milder forms of SDB, including Upper Airway Resistance Syndrome (UARS), can be detected. PSG’s are essential to the diagnosis of SDB in hypermobile patients.
Onabotulinum Toxin Serves as an Effective Treatment for Chronic Daily Headache in Patients with Hypermobility Syndromes
Hypermobility syndromes (Hypermobility Spectrum Disorder, Hypermobility Syndrome, Ehlers–Danlos Syndrome Hypermobile type) are a group of connective tissue disorders characterized by joint laxity. Due to the nature of our patient population, our headache clinic has an unusually high occurrence of patients with this disorder. These patients have been found to experience a high prevalence of Chronic Headache Disorder. We previously found that the higher than normal incidence of headache is caused by unstable cervical in-tervertebral joints leading to the transloca-tion of cervical vertebrae on flexion and ex-tension. Onabotulinum Toxin A (Botox, Aller-gan) is an effective prophylactic treatment for Chronic Headache Disorder. Patients with Hy-permobility Syndromes have a high failure rate of standard prophylactic therapy, while Botox has been indicated to work well. These patients also experience a plethora of symp-toms including dysautonomia, sleep disor-dered breathing, and joint pain.
Nephroprotective Effects of Substituted Cyclodextrins
Many intravenously administered drugs are removed from the body through the kidneys, where they are highly concentrated before elimination in the urine. Many of these IV drugs cause nephrotoxicity, ranging from mild reversible decreases in creatinine clearance, to total kidney failure requiring transplantation, to death. One of those nephrotoxic drugs, methotrexate, was being investigated as a treatment for multiple sclerosis, but therapy required close monitoring and control to minimize potential kidney toxicity. A substituted cyclodextrin (SCD) was employed with the methotrexate to determine if the cyclodextrin could solubilize the drug in the kidney and minimize its damage. The results were very positive even though SCD are themselves known to have the potential to cause kidney toxicity at certain doses. Surprisingly, the nephroprotection was probably not by a drug solubilization mechanism since further investigation showed the best activity at SCD:methotrexate mole ratios less than one and pronounced activity was also seen with highly water soluble nephrotoxic drugs. This report describes those studies and lays the groundwork for a new use for cyclodextrins.
Role of Hypermobility in Headache and Migraine
Joint Hypermobility Syndrome (JHS) seems to have an unusually high prevalence in patients who come to our headache center. Most of these patients also have additional symptoms of Dysautonomia (DYS), Sleep Disorders (usually Sleep Disordered Breathing (SDB)), and Disorders of the Cervical Spine (DCS). Therefore, it seemed appropriate to study the relationship between JHS, Headache, Sleep Disorder, and DYS.
Evaluation of Sleep Disordered Breathing in Hypermobile Patients
The prevalence of Joint Hypermobility Syndrome (JHS) worldwide is estimated to be 5-17%1. Hypermobility syndromes have been associated with a variety of comorbidities, and can be an important risk factor for Sleep Disordered Breathing (SDB). The usual risk factors for SDB, such as obesity, male gender, or post-menopausal status, are frequently absent in hypermobile populations, yet the impact of SDB on the quality of these patients’ lives can be profound.
Treatment of Sleep Disordered Breathing in Hypermobile Patients
Patients with hypermobility syndromes often have difficulty using Positive Airway Pressure (PAP) Therapy for treatment of their Sleep Disordered Breathing (SDB). To investigate this, the CPAP titrations of patients with hypermobility and SDB were studied in detail.