Abstract
We report two patients with reversible cerebral vasoconstriction syndrome (RCVS) and carotid glomus tumour. The first patient presented with multiple thunderclap headaches. Cervical and cerebral magnetic resonance imaging showed diffuse cerebral vasoconstriction on magnetic resonance angiogram (MRA) and a carotid glomus tumour. The second patient presented with a cervical mass and was diagnosed with a non-secreting paraganglioma of the carotid body. Surgery with pre-operative angiography was followed by thunderclap headaches and MRA showed segmental cerebral vasoconstriction. Both patients were treated with nimodipine and headaches stopped. Both had normal cerebral arteries on the control MRA at 3 months. These two cases suggest that a paraganglioma may increase the susceptibility to develop RCVS. As a consequence, patients with RCVS should be investigated for a carotid glomus tumour, and patients with paraganglioma reporting severe headaches should have a cerebral MRA in order to rule out cerebral vasoconstriction.
Keywords
Introduction
Reversible cerebral vasoconstriction syndrome (RCVS) is characterised by the association of severe headaches with or without focal neurological deficit, and a reversible cerebral vasoconstriction assessed by an initial angiography (MR, CT or conventional angiography), with disappearance of arterial abnormalities within less than 3 months demonstrated by a repeat angiography (1,2). This condition affects both genders, with a female preponderance (3,4). The mean age of onset is around 40 years old (1–4). Recurrent thunderclap headaches, defined as severe headaches peaking in less than 1 min, are the clinical hallmark of RCVS (1,3–6). More than half the cases occur in special circumstances such as postpartum or after an exposure to various substances such as vasoconstrictors (1,3,4). Less frequently, RCVS has been described in patients with catecholamine-secreting tumours (7,8), after head or neck injuries such as head trauma (9), post carotid endarterectomy (10), and neurosurgical procedures (1). In some secondary forms of RCVS, a single favouring factor or associated condition is identified; in others, multiple favouring factors or conditions are found (4).
Glomus tumours, also called paragangliomas, are slow-growing vascular lesions originating from non-chromaffin cells, arising from glomus bodies (11). In the head and neck area, they can be located in the middle ear cavity (glomus tympanicum tumour), in the dome of the jugular bulb (glomus jugulare tumour), in the ganglion nodosum of the vagus nerve (glomus vagale tumour), and on the carotid body near the carotid bifurcation (carotid body tumour). Less than 5% of paragangliomas are catecholamine-secreting tumours and only a few patients report headaches (12,13). We report the cases of two patients with paraganglioma and RCVS.
Case reports
Case history 1
A 51-year-old woman with a history of treated hypothyroidism and without any past history of headache, had five thunderclap headaches over a 19-day period. All those headaches had a very severe intensity, peaked in a few seconds, were bilateral and diffuse, and lasted 30–120 min. Two were triggered by a hot shower, one by a mild physical effort, and two started without any trigger. Her neurological and general examinations were normal. Blood-pressure was 118/87 mmHg. A magnetic resonance imaging (MRI) with angiography (MRA) was performed on the 23rd day after headache onset, and showed segmental and multifocal vasoconstriction of cerebral arteries. The cerebral parenchyma was normal. Cervical MRA revealed a 3-cm mass behind the right internal carotid artery. Further investigations were carried out: OctreoScan was positive, urinary catecholamine excretion was in the normal range, and cervical contrast-enhanced CT scan showed a typical aspect of paraganglioma of the carotid body, i.e. a strongly enhancing soft-tissue mass along the course of the carotid artery. Nimodipine was started on day 23, at the dose of 60 mg every 8 h, and thunderclap headaches did not recur. On day 35 after onset, the patient had a transient episode of positive bilateral visual symptoms during 3 min, followed by a moderate, right-sided, orbital headache lasting half a day. This episode was regarded as a possible transient ischaemic event in the basilar artery territory. Nimodipine was reduced to 30 mg every 8 h after 1 month and stopped after a total duration of 2 months. A control MRA at 3 months was normal, validating the diagnosis of RCVS. The headaches apart, the paraganglioma was asymptomatic. The patient was informed that the tumour could be either looked after, or treated by surgery or radiotherapy. There was no headache recurrence within the 24 months of follow-up.
Case history 2
A 39-year-old man discovered a left cervical mass by self-palpation. There was no other symptom, and no past history of headache. Examination, cervical tomodensitometry, MRI with MRA (Figure 1A), OctreoScan and urinary catecholamine dosages revealed a non-secreting paraganglioma of the left carotid body. A surgical resection was decided. The week before surgery, the patient had influenza and used a nasal-decongestant spray containing naphazoline. During the test occlusion performed during the pre-operative angiography (Figure 1B), the patient reported a very sudden and short-lasting (10 s) diffuse headache that immediately stopped when the occlusion was removed. Surgical resection was performed, and showed an oblong tumour located between the internal and external carotid arteries. Meticulous dissection allowed preservation of all the vessels but the superior thyroid artery. There was no temporary occlusion of the carotid artery. Blood pressure and cardiac rhythm remained normal throughout the procedure. Pathology confirmed the diagnosis. Between days 12–20 after the first sudden headache, the patient had four thunderclap headaches with very severe bilateral pain lasting 5–15 min, followed by a moderate headache lasting 24 h. Two of these thunderclap headaches were triggered by sexual activity and two by exertion. Neurological examination was normal. Blood-pressure was 136/85 mmHg. A cerebral MRI with MRA, performed on day 21 after the first headache, showed a diffuse segmental vasoconstriction (Figure 2A). Nimodipine was started at the dose of 60 mg every 8 h, and no other severe headache occurred. A normal MRA at 3 months confirmed the diagnosis of RCVS (Figure 2B). The patient was advised to avoid all vasoactive medications. Ten months later, he complained of anxiety and was prescribed paroxetine. From days 3–6 of treatment, he had four moderate orgasmic thunderclap headaches. He did not seek medical advice but remembered he should avoid such medications. He stopped paroxetine and orgasmic headache stopped. No other unusual headache occurred during the following year.
Cervical imaging in paraganglioma. Case 2 had a left cervical mass that revealed a left carotid glomus tumour visible on the cervical magnetic resonance angiography (A) and the pre-operative catheter angiography (B). Reversible vasoconstriction of the basilar artery. Case 2 had a segmental cerebral vasoconstriction including a marked narrowing of the upper part of the basilar artery on cerebral magnetic resonance angiography (A) with complete normalisation on the control performed within 3 months of headache onset (B).
Discussion
These two patients had a definite RCVS associated with a paraganglioma. To our knowledge, this association has not been previously reported. Most glomus tumours are revealed by the presence of a cervical mass, or rarely by cranial nerve paralysis (X, XII in most cases) (11). Only 4% of these tumours secrete catecholamines, which may cause severe hypertensive crises and subsequent severe headaches and/or strokes (12,13). However, in the few published patients with catecholamine-secreting paragangliomas and headaches, the diagnosis of RCVS has never been suggested, and none of these patients had a cerebral MRA.
In both patients, the diagnosis of RCVS was established on the basis of typical clinical features (recurrent thunderclap headaches) and a reversible vasoconstriction of cerebral arteries assessed by an initial MRA showing characteristic ‘strings and beads’ followed by a control MRA within 3 months showing normalization (1). In the first patient, exhaustive investigations were performed because of acute headaches and led to the concomitant identification of cerebral vasoconstriction and of a paraganglioma. In the second patient, who had a cervical mass consistent with a carotid glomus tumour, pre- and postoperative thunderclap headaches led to the diagnosis of RCVS. This latter patient also took an α-sympathomimetic the week before surgery. In both cases, the paraganglioma was a non-secreting carotid body tumour, and the outcome of RCVS was good, without cerebral haemorrhage or infarction. During follow-up, the first patient had no recurrence, and the second patient had multiple orgasmic thunderclap headaches that started after 3 days of treatment with a selective serotonin recapture inhibitor (SSRI) and stopped when this medication was discontinued. This second episode of multiple thunderclap headaches strongly suggests a recurrence of RCVS. However, a definite diagnosis was not possible, as the patient did not seek medical attention. Prospective follow-up studies of large series of patients are needed to study the frequency and the risk-factors of recurrence in RCVS.
RCVS includes the association of cardinal angiographic and clinical features, namely, a reversible segmental and multifocal vasoconstriction of cerebral arteries, and severe headaches with or without focal neurological deficits or seizures (1,3). During the last decade, RCVS has been increasingly recognised as a separate syndrome due to a transient and reversible disturbance of cerebral arterial tone regulation without inflammation (4–6). However, the precise underlying mechanisms are unknown. More than half the cases occur in special circumstances (1,4). The main potential trigger factors of RCVS are post-partum and exposure to various vasoactive serotoninergic and sympathomimetic substances (mainly cannabis, SSRI and nasal decongestants) (1,3,4). RCVS has also been described in association with catecholamine-secreting-tumours such as pheochromocytoma (7,8) or bronchial carcinoid tumour, metabolic disorders such as hypercalcaemia or porphyria (1), and after various cervical or cranial ‘traumas’, such as carotid endarterectomy (10), head trauma (9), and neurosurgical procedures (1). Finally, RCVS may be associated with cervical or cranial large artery lesions such as cervical artery dissection, unruptured saccular cerebral aneurysm, or cerebral arterial dysplasia (4). In our first patient, a woman, with RCVS and paraganglioma, none of these known associated conditions was found. In our second patient, a man, multiple potential trigger factors were present including exposure to naphazoline, carotid clamping during angiography, and direct arterial manipulation during surgery. In addition, this man had a probable recurrence of RCVS (without angiographic confirmation) after exposure to SSRI. It was previously suggested that RCVS occurs in patients with a predisposition to develop diffuse cerebral vasoconstriction (1–4), and that this susceptibility was higher in females than in males, in whom exposure to multiple vasoactive substances and/or co-occurrence of multiple potentially triggering factors are often required for a RCVS to develop (4).
Although the association of RCVS and carotid paraganglioma could be purely coincidental, we propose that a glomus tumour should be regarded as a potential factor increasing the susceptibility to develop reversible cerebral vasoconstriction, and hope that our report will stimulate further reflection on the relationship between this enigmatic syndrome and the numerous associated conditions. The mechanisms linking paraganglioma and RCVS remain entirely speculative. Our first hypothesis is that an undetected adrenergic secretion of the paraganglioma could have played a role in the outbreak of RCVS. Indeed, some glomus tumours are catecholamine-secreting, and RCVS due to catecholamine-secreting tumours has been reported (7,8). Our two patients had urinary catecholamine excretion in the normal range. However, some patients with non-secreting glomus tumours according to negative urinary tests may complain of typical symptoms of catecholamine secretion, such as flushes, sweats, or headaches (B. Verillaud, personal data). Moreover, in asymptomatic patients with an unsuspected pheochromocytoma, the inadvertent use of vasoconstrictors such as ergots or pseudoephedrine has been shown to provoke severe headaches and, sometimes, posterior reversible encephalopathy syndrome (14) or cardiac failure (15). In our second patient, the use of nasal decongestant could have interacted with a minimal undetected catecholamine secretion to increase the susceptibility to RCVS.
Our second hypothesis is that the susceptibility to RCVS in both patients could have been augmented by a direct mechanical effect of the tumoural mass on the internal carotid artery. In our second patient, this supposed mechanical effect could have been further increased first, by the pre-operative angiography with test occlusion that triggered the first thunderclap headache, and second, by the surgical excision of the paraganglioma. This hypothesis is supported by the fact that RCVS has been described after other surgical procedures involving the carotid artery, like carotid endarterectomy (10), and also in association with spontaneous cervical artery dissections (4).
Conclusions
These case reports have three main clinical implications. First, patients with cervical paraganglioma should be investigated for a RCVS when they report unusual headaches, especially in the postoperative period. Second, patients diagnosed with a RCVS should be carefully interviewed and examined for signs of a glomus tumour, and a cervical CT or MRI should be performed to detect a sub-clinical tumour. Finally, patients diagnosed with a RCVS should be cautioned to seek medical advice in case of a new episode of thunderclap headaches, in order to identify a recurrence of RCVS.