Data on headaches in patients with hereditary diseases, in particular Marfan syndrome, are few and scattered. We present episodic cephalgia in a patient with Marfan syndrome.

A 35-year-old patient appealed for specialized care due to attacks of unilateral and bilateral severe headache accompanied by nausea and vomiting. In 30% of cases, seizures were preceded by visual disturbances. The patient described looking "through the broken glass", and these violations were more common in the left visual field. Visual disturbances lasted about 20 minutes. Headache developed within 1-1.5 hours after these disorders. Duration of headache was up to 25 hours. The patient noted prodromal signs (weakness, drowsiness) within a day before headache. He called physical tension and lumbar spine extension as typical provoking factors. He used lumbar spine extension as a marker of further attack. Headache occurred 4-5 times a month. Attacks were not associated with transition to vertical position.

The patient has suffered from headache attacks since 16-year-old age with remissions up to 5 months. Ketorol, nimesulide, aspirin, Sedalgin and Katadolon were used for pain relief. Triptans prescribed for migraine were ineffective.

The patient is a disabled person (grade 2) due to Marfan syndrome. He has previously undergone mitral valve replacement and implantation of pacemaker in 2019. He also suffers from severe myopia (-11D). The patient denied family history of Marfan syndrome. However, the patient's mother died at the age of 27 years from aortic dissection.

There were no focal neurological symptoms. The patient is tall (192 cm) and asthenic.

CT of the brain (2019) revealed no abnormal changes. CT angiography (2019) revealed S-shaped tortuosity of internal carotid and vertebral arteries, as well as a variant of circle of Willis (no blood flow in posterior communicating artery). EEG (2019) revealed no abnormalities. MRI of cervical spine (2016, 2019) diagnosed degenerative-dystrophic lesions, protrusions of C3-C4, C4-C5 discs. Lumbar puncture was performed in March, 2020 (colorless transparent cerebrospinal fluid under normal pressure). Analysis of cerebrospinal fluid: protein 0.29 g/l, cytosis 2 (lymphocytes), glucose 3.35 mmol/l, chlorides 116.9 mmol/l.

MRI of the lumbar spine revealed multiple meningoceles at the lumbar level (Figure).

MRI. Multiple meningocele.

Genetic examination regarding CADASIL syndrome was carried out. No abnormal variants in zones 1–6 and 11 of the NOTCH3 gene were found. However, these data do not rule out CADASIL syndrome.

Neurosurgeon recommended in-hospital management for analysis of indications for surgical treatment. The patient was discharged ahead of schedule due to the COVID-19 pandemic.

He received warfarin, sotahexal, torasemide, acetazolamide, gabapentin, teraligen, phenibut, cerebrolysin, cytoflavin, amitriptyline, cortexin and topiramate without effect.

Diagnosis: Marfan syndrome. Congenital spinal cord anomaly (multiple lumbar meningoceles) with impaired CSF circulation. Secondary headache with visual disturbances probably associated with intracranial hypertension. Previous mitral valve replacement and implantation of pacemaker in 2019.

Acetazolamide intake and repeated consultation by neurosurgeon regarding surgical treatment of meningocele were recommended.

Discussion

Migraine is a clinical diagnosis and can be erroneously established in some other diseases and conditions accompanied by cephalalgia with similar characteristics. In addition, there are certain diseases with migraine (including migraine with aura) as a component of clinical picture (for example, CADASIL syndrome).

In our case, severe unilateral and bilateral headache lasting up to 25 hours with nausea and vomiting, reversible visual disturbances preceding the attack and lasting about 20 mi and prodromal signs almost completely meet the diagnostic criteria of the International Headache Society (IHS) for migraine with aura (typical aura with headache). At the same time, provoking factor of headache (lumbar spine extension) was an atypical sign for migraine.

Marfan syndrome is an autosomal dominant hereditary connective tissue disease manifested by lesions of musculoskeletal, cardiovascular systems, eyes, skin and meninges. The most severe and life-threatening ones are cardiovascular disorders, including aortic and heart valve diseases [1]. The prevalence of Marfan syndrome ranges from 1:5,000 to 1:10,000 with equal ratio of males and females. Over 1000 genetic mutations are associated with Marfan syndrome. In most cases, dominant mutation of the FBN1 gene on chromosome 15 encoding fibrillin-1 is detected. Family history is typical in 75% of patients, and “new” mutation is assumed in other ones [2]. Currently, the diagnosis is established in accordance with the revised Ghent criteria (2010) [2].

Cardiovascular diseases including aortic dissection [1], aneurysm [3], heart valve defects, as well as musculoskeletal disorders and lens ectopia [4, 5] are the most common in Marfan syndrome. Neurological symptoms of Marfan syndrome are mainly associated with damage to the meninges. Dura mater ectasia occurs in 63-92% of adults with Marfan syndrome (most often in lumbosacral spine). Ectasia is followed by back pain, headaches, motor and sensory disorders in the lower extremities [6, 7]. Symptoms are usually aggravated by standing upright and relieved by lying down. Dural ectasia leads to violation of cortical layer of vertebral bodies and anterior meningocele [8]. Spontaneous dura mater ruptures with intracranial hypotension have been described in patients with Marfan syndrome [9, 10]. Spinal cord hypermobility [7] and cerebrovascular disorders following cardiogenic embolism [11] are also discussed.

Pain syndromes are common in Marfan syndrome (47-91.5% of cases) caused by musculoskeletal abnormalities in most cases [12]. Data on headaches in patients with Marfan syndrome are presented by few case reports. Vandersteen A.M. et al. [11] reported persistent retroorbital cephalgia in a patient with Marfan syndrome and asymptomatic ophthalmic artery aneurysm. Sakakura S. et al. [13] described classic trigeminal neuralgia in a patient with Marfan syndrome, basilar artery elongation and neurovascular conflict. Migraine was noted in a patient with Marfan syndrome and aortic dissection [14]. Bekavac I. and Halloran J.I. [15] described a patient with syncope and lumbar meningocele. The authors noted visual disturbances preceding headaches. In their opinion, symptoms were associated with intracranial hypertension following compression of meningocele.

Obviously, the mechanism of headache is similar in our patient with visual disturbances. Lumbar spine extension reducing anteroposterior dimension of spinal canal probably contributes to episodic intracranial hypertension and cephalgia with visual disorders.

Management of patients with meningocele includes neurosurgical care in addition to symptomatic therapy [16].

The purpose of this report was to acquaint specialists with a rare variant of secondary headache.

The authors declare no conflicts of interest.