This narrative review by Martin VT & Neilson D (2014) is on the relevant research related to headaches associated with Hypermobile Ehlers-Danlos Syndrome (hEDS) and Marfan syndrome as these were the most studied Connective Tissue Disorders (CTDs) in current literature. This paper was published in the Headache journal by the American Headache Society. The first author, Martin V.T is from the Department of Internal Medicine of the University of Cincinnati at the United States of America.
The authors searched PubMed for articles with terms including joint hypermobility, joint hypermobility syndrome, EDS, Marfan syndrome, and specific headache disorders (e.g. migraine, cervical artery dissection, Arnold Chiari malformation, intracranial hypotension, atlanto-occipital instability, cervical disc disorders, cervical hypermobility, and temporomandibular disorders (TMD).
The underlying causes related to migraine headaches are currently unknown. However, the information outlined below will detail some prevalence statistics and proposed mechanisms related to migraines.
- Prevalence of migraines in hEDS:
- Based on 3 articles published from 1999 to 2011, hEDS was found to be associated with migraine headaches. The study designs were of low quality- case series or case control/cohort.
- One of these studies found that 40% of 170 patients with hEDS were diagnosed with migraine compared to 20% in a control population.
- Another study found migraine was 3.2 times more prevalent in patients with hEDS than controls.
Frequency of migraine attacks was found to be 1.7 times increased, and headache-related disability was 3.0 times greater in patients with hEDS compared to controls.
- Prevalence of migraines in Marfan syndrome:
- Based on 3 studies published from 2006 to 2012, the prevalence of migraine was also found to be increased in patients with Marfan syndrome.
One of the studies reported a 63% prevalence of migraines in people with Marfan syndrome.
- Another study found that the prevalence of migraine was increased by 1.9 times in those with Marfan syndrome compared to matched controls.
Potential mechanisms related to migraine in patients with EDS-HT/JHS and Marfan syndrome
Several potential mechanisms were proposed to explain the increased prevalence of migraine in patients with CTDs in general.
- Firstly, it is known that CTDs including Marfan syndrome, and vascular type EDS are associated with aortic dissections, aneurysms, and valvular heart diseases. The authors proposed that migraines are related to damaged vascular wall linings (endothelium) resulting in weakening of the vascular wall or accumulation of clots (artheroemboli) in vessels within the brain.
- Secondly, patients with CTDs such as Marfan syndrome commonly have right-to-left shunts detected on transcranial Doppler which could predispose them to migraine attacks from blood clots (thromboembolism).
- Thirdly, dysautonomia which is also commonly associated with patients with CTDs including hEDS and Marfan could be a cause of migraine due to adrenergic hyperfunction. Additionally, migraine has been found to be highly prevalent in people with postural orthostatic tachycardia syndrome (POTS), which is a type of dysautonomia and highly prevalent amongst patients with CTDs.
- Fourth, migraines may be associated with abnormalities of TGF-beta signalling pathways, which could be related to the pathogenesis of migraines. Reportedly, some studies have shown that medications that reduce TGF-beta signalling such as angiotensin receptor blockers were effective in preventing migraines.
Medical Management for Migraines
- A study referenced by the authors reported that muscle relaxants such as tizanidine and baclofen might be avoided as cervicogenic or tension headaches may be triggered to due increase in neck mobility. For the same resons, it was also recommended that injections of onabotulinum toxin A not be injected into neck muscles.
- The authors recommended use of anti-hypertensive medications as preventatives with caution especially for those with orthostatic hypotension and low blood pressures. Small doses of beta-blockers were suggested to reduce migraine frequency and POTS symptoms.
- The authors reported success with topiramate, tricyclic anti-depressants, gabapentine, and valproic acid as preventative medications based on their own clinical experiences.
Intracranial Hypotension/CSF Leaks
Cerebral Spinal Fluid (CSF) leak may be suspected in those with orthostatic headaches, i.e. headaches aggravated by being upright (standing) and improved in a lying down, supine position.
In one study, 66% of patients with spontaneous CSF leaks were associated with subtle signs of CTDs. CTDs may be associated with CSF leaks due to laxity of the dura.
Dysautonomia and Coat-Hanger Headaches
Dysautonomias were found to be correlated with “coat-hanger headaches” in some studies, i.e. headaches aggravated by moving to upright positions.
“Coat-hanger” headaches are located in at the base of the skull (occipital), neck, and shoulder regions in a “coat-hanger” distribution.
The authors proposed support stockings and fludrocortisone as initial medical therapies to relieve symptoms followed by midrodrine if those treatments failed to work. They also proposed beta blockers in low dosages in those with hyperadrenergic form of POTS.
Chiari Malformation Type 1 (CM1)
CM1 is a developmental disorder of the lower part of the brain resulting in a downward displacement of the brain.
The downward displacement puts pressure on the brainstem and cranial/cervical nerves, obstructs flow of CSF in the region, and also compresses on the blood vessels in brain such as the vertebral artery and posterior inferior cerebellar artery (PICA). Headaches at occipital and suboccipital regions have been reported in those with CM1, and the symptoms are often aggravated by activities that increase intra-cranial pressures such as coughing, Valsalva maneuvers, exertion, and head dependency. The authors noted that patients with CM1 and CTD were more likely to suffer from POTS, sleep apnea, cervical spine subluxation and/or atlantoaxial instability, dysphagia and nausea.
Carotid Artery Dissections (CADs)
CADs result from a tear or lesion in the carotid artery.
It can be associated with a spontaneous mechanism, or occur after activities such as coughing, chiropractic manipulations, and trauma (e.g. sports, whiplash injury). It often presents as headache on the one side (unilateral).
New Daily Persistent Headache (NDPH)
NDPH are continuous headaches that commence on a specific day for 24 hours after onset. They are usually on both sides (bilateral) and 64% report throbbing or pressure like symptoms. They can be in the occipito-nuchal and retro-orbital regions of the head. The underlying cause is unclear but they are often preceded by infection, recent hysterectomy, or stress. One study found evidence of neck hypermobility in 12 patients with NDPH.
It was proposed that hypermobility of the neck causes NDPH due to irritation of the C1 to C3 cervical afferent nerves that converges on the trigeminal nucleus of the brainstem with the trigeminal nerve.
Physiotherapy focusing on muscle strengthening to stabilise the hypermobile neck, activity modification, posture retraining, and proprioceptive training is the treatment of choice.
Cervicogenic headaches are headaches originating from the neck (cervical spine).
Causes of cervicogenic headache reported in literature include cervical facet arthropathy, tumours/fractures/infections/trauma of the upper cervical spine, C2 neuralgia, neck tongue syndrome, occipital neuralgia, and atlantoaxial arthritis/instability. Other less studied causes include cervical disc herniations, cervical spondylosis, scoliosis and spinal stenosis. In a study, 61% of patients report headaches in the occipital area, with a mild to moderate intensity, and of daily frequency.
Atlantoaxial instability can be diagnosed via flexion and extension x-rays or MRIs of the cervical spine but is best examined by rotational 3D CT scan to identify rotational instability of the craniocervical structures.
Management consists of physiotherapy except for those with atlantoaxial instability. Injections such as epidural steroids or facet blocks may be used in those with herniated discs or facet hypertrophy. Surgical interventions such as laminectomy and cervical fusion for cervical disc disorders, may be done in patients who fail conservative therapies. Those with atlantoaxial instability require neurosurgical consultation about the need to stabilise C1 and C2 surgically.
Temporomandibular Disorders (TMDs)
TMDs are diagnosed using clinical or radiographic scans.
Headaches are reported in the temporal/masseter regions and is triggered by worsening of the TMD. TMD is associated with migraine and chronic daily headaches.
Patients with joint hypermobility have increased jaw opening (>40mm from upper to lower incisors) and are more prone to jaw dislocations. A study also found jaw clicking to be 1.7 times more likely in hypermobile patients than controls. Physiotherapy intervention, patient education and occlusive splints are the proposed management strategies.
Medication Overuse Headaches
A study found that patients with EDS have on average 8 different pain locations, and 51% were taking chronic narcotics for pain relief.
As EDS can be a multi-system disorder, if it common for patients to have medication overuse and related headaches. The authors recommend a multi-modal and multi-disciplinary approach.
Headaches and migraines in people with hEDS/EDS and Marfan syndrome can be associated with a variety of reasons.
The reasons are as follows:
- Migraine headaches
- Intracranial hypotension/CSF leaks
- Dysautonomia and “coat-hanger” headaches
- Chiari Malformation Type 1
- Carotid Artery Dissections
- New Daily Persistent Headaches
- Cervicogenic Headaches
- Temporomandibular Disorders
- Medication Overuse Headaches
- Others (not reported in this review)
- Combination of the above
Post by: drchenphysio.com
Limitations of this Review
As this is a summary narrative review, the contents written in this review do not encompass all literature related to headaches in those with hEDS and Marfan syndrome, and as such should be read and applied with discretion. Note that narrative reviews, albeit useful resources, are scientific evidence with a high risk of bias as a systematic, or more reproducible methodological approach was not applied in the crafting of such papers. An example of a study design with low risk of bias is a systematic review with meta-analysis, which was probably not applied in this paper due to scant existing research. This is also a summary review of the published paper, so readers beware that not all information from the original article may have been captured in this blog post.