Posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome after bilateral carotid paraganglioma resection: A case report

Introduction

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by severe headaches with or without seizures and focal neurological deficits associated with constriction of the cerebral arteries as assessed by angiography, which spontaneously resolves in 1–3 months (1). Approximately 60% of RCVS cases are secondary, mainly to post-partum conditions or after exposure to vasoactive drugs (1). More rarely, RCVS has been described in patients with catecholamine-secreting tumours or carotid glomus tumours (2).

We report a case of a patient with RCVS associated with a posterior reversible encephalopathy syndrome (PRES) following surgery for a left carotid paraganglioma a few months after resection of a right carotid paraganglioma.

Case report

A 43-year-old woman was admitted to our Department of Neurology for two successive generalized tonic–clonic seizures preceded by clonic seizures of her left upper limb. Her past medical history comprised migraine without aura, cholecystectomy and appendectomy. She discovered a bilateral cervical mass by self-palpation and had been suffering from right tinnitus for several years. She was first operated on for her right class III carotid paraganglioma without any local or general complications; blood pressure remained normal throughout and after the surgery. Five months later, resection of her left carotid paraganglioma had been performed without any temporary occlusion of the carotid artery. Blood pressure and cardiac rhythm remained normal throughout the surgery and during the first 4 days of hospitalization. However, 4 days after surgery, she complained of several episodes of ‘thunderclap headaches’, often triggered by coughing, which was likely to be due to tracheal irritation induced by intubation. Her headache crises were characterized by very severe pain localized in the frontal and occipital areas bilaterally and lasting 10–20 minutes, and were followed by a moderate headache lasting several hours and blurred vision. During this time period, the patient experienced severe arterial hypertension with systolic blood pressure levels of up to 240 mmHg. Seven hours after headache onset, the patient had two episodes of simple partial seizures with motor symptoms followed by secondary generalization and post-ictal state. A few hours later, the neurological examination was fully normal, except for mild dysphonia due to the recent intubation.

Brain magnetic resonance imaging (MRI) was performed and showed a bilateral occipital mild T2 fluid attenuation inversion recovery hypersignal (predominantly on the right side) without any sign of stroke; vasospasms were observed in multiple cerebral arteries, leading to a diagnosis of a PRES with signs of RCVS. Electroencephalogram showed no abnormalities. Echocardiography, electrocardiogram and 24-hour electrocardiography were normal. Doppler ultrasonography of the cervical arteries was normal on both sides, but still showed a hyperechogenic and heterogeneous hypervascularised process next to the right carotid artery. Whole-body scintigraphy octreoscan was positive for the two carotid paraganglioma (predominant on the right side) in spite of the surgery, but no other metabolic activity was observed. Her laboratory values were all normal without renal insufficiency. Urine catecholamines (epinephrine, norepinephrine and dopamine) and metanephrine levels were normal. Cerebrospinal fluid analysis was normal.

Urapidil (10 mg intravenously, followed by infusion: 4 mg/hour for 5 hours) and nimodipine (at a dose of 60 mg every 8 hours) were started. Coughing progressively decreased over a few days, and blood pressure remained stable (systolic blood pressure under 140 mmHg; diastolic blood pressure under 90 mmHg). Urapidil was rapidly stopped because of normalization of blood pressure; nimodipine was progressively stopped after a total duration of 1 month. Four weeks after the beginning of the RCVS, 24-hour ambulatory blood pressure monitoring demonstrated mean systolic blood pressure at 106 mmHg (peak 148 mmHg) and mean diastolic blood pressure at 68 mmHg (peak 106 mmHg). There were no hypertensive crises. However, an alteration in the baroreflex was demonstrated by simultaneous recording of spontaneous fluctuations in blood pressure, noninvasively monitored by a finger plethysmograph (Finapres 2300™, Ohmeda BOC, Inc., USA) (3), and pulse interval, measured by standard 12-lead ECG, applying the sequence method (4,5). Low values of baroreceptor sensitivity were found in both supine (2.8 ms/mmHg) and standing positions (1.8 ms/mmHg).

At 3 months, blood pressure and clinical examination were both normal, and the patient did not present any other seizures (without anticonvulsant treatment) or headaches. At 3 months, a normal MRI and magnetic resonance angiography (MRA) confirmed the diagnosis of RCVS.

Discussion

Paragangliomas are slow-growing and highly vascular neoplasms that are usually benign (malignant forms represent 5–15% depending on the location of the tumour); they can be divided into non-functional or, more rarely (less than 5%), functional tumours that secrete catecholamines, which may lead to severe hypertensive crises, headaches and sometimes strokes (6). Based on location, two subtypes of paraganglioma are distinguished: they may appear in the adrenal medulla (such as pheochromocytoma) or in extra-adrenal tissues (arising anywhere along the paravertebral sympathetic and parasympathetic chains in head, neck, abdomen, retroperitoneum, chest and mediastinum) (6). The typical presentation of paragangliomas depends on their location; most symptoms are related to the mass effect that the tumour produces, ranging from tinnitus, vertigo and hearing loss in temporal bone tumours to a painless neck mass or cranial nerve deficits in carotid body and base-of-skull paragangliomas (6). Sixty percent of head and neck paragangliomas are carotid body tumours (CBTs) situated at the bifurcation of the common carotid artery (within the adventitia), followed by jugulo-tympanic paragangliomas (nearly 40%), vagal paragangliomas (<5%) and, more rarely, orbit, nasopharynx and larynx paragangliomas (7). CBT is a slow-growing tumour, also called ‘extra-adrenal paraganglioma’, ‘glomus tumour’ or ‘chemodectoma’. It has been classified on the basis of ease of surgical removal: ‘class I’ tumours are small and easily resected, ‘class II’ tumours are larger but still easily resected by subadventitial dissection and ‘class III’ tumours encase the carotid body and require partial or complete carotid resection and reconstruction (8). CBTs are painless; their most frequent symptom is a palpable neck mass located below the angle of the mandible, which is mobile not vertically but laterally because of its adventitial attachments. Additional symptoms are hoarseness, dysphagia, stridor, dizziness, progressive neighbouring cranial nerve palsies, Horner’s syndrome, airway obstruction and, exceptionally, RCVS (2).

Only two other cases of RCVS have been observed in a context of untreated non-secreting carotid paraganglioma (2). In one patient, RCVS revealed a glomus tumour when cervical and intracranial MRA was performed after five episodes of ‘thunderclap headaches’; in the second patient, four ‘thunderclap headaches’ occurred 12–20 days after surgical resection of a left cervical paraganglioma (one episode also occurred during the occlusion test performed during the preoperative angiography and immediately stopped when the occlusion was removed). However, this patient had taken an α-sympathomimetic (nasal decongestant spray containing naphazoline) during the week before surgery (Figure 1). None of the patients experienced severe hypertensive crises during RCVS and follow-up. OPEN IN VIEWER

RCVS was initially observed in post-partum conditions. This clinical and radiological syndrome includes the hyper-acute onset of severe headaches and segmental vasoconstriction of cerebral arteries that resolves by 3 months (9). RCVS can occur spontaneously, but can also be secondary to an identifiable trigger (vasoactive medications, vasoactive recreational drugs, pregnancy/post-partum, blood products, carotid dissection, pheochromocytoma, etc.) (9). In some cases, as in our patient, RCVS occurs in subjects with a history of migraine (in 20–40% of cases) and it might be triggered by Valsalva-like manoeuvres such as coughing, although such an association may be coincidental considering the potential delay between exposure and the development of the syndrome, as well as the ubiquity of these possible triggers (9). Aside from CBT, RCVS has been described in other pathologies of the internal carotid artery such as post-carotid endarterectomy (10) and internal carotid artery dissection (11). An association of RCVS and cervical artery dissection (CeAD) was observed in 12% of patients with RCVS and in 7% of patients with CeAD (11).

The PRES observed in our patient has been reported in 17–38% of patients with RCVS, and vasoconstriction is present in approximately 15–30% of patients with PRES who undergo angiography (12). PRES consists of a reversible subcortical vasogenic brain oedema occurring in various conditions such as renal failure, blood pressure fluctuations, cytotoxic drugs, autoimmune disorders, pre-eclampsia/eclampsia, infection/sepsis, shock, cancer and hypercalcaemia (12). Cerebral haemorrhage, restricted diffusion, contrast enhancement and vasoconstriction are also compatible with PRES (12), which is clinically characterized by a constellation of symptoms including seizures (60–75%), at times with status epilepticus (5–15%), headache (50%), altered mental status and encephalopathy (50–80%), visual disturbances (33%) and focal neurological deficits (10–15%) (12). The association of RCVS, PRES and CBT could be coincidental, but different mechanisms linking these situations could be evoked, although they remain speculative.

Adrenergic secretion of the paraganglioma could have played a role in the occurrence of RCVS, but our patient, as with the two other cases published in the literature (2), had urinary catecholamine excretion in the normal range. A second hypothesis could be a consequence of the direct compression of the carotid internal artery by the CBT (increasing susceptibility to RCVS) (2); this hypothesis may be supported by the description of RCVS occurring in association with spontaneous carotid artery dissection (11) or after carotid endarterectomy (10). Finally, RCVS could be the consequence of a failure of the baroreceptor reflex (comprising hypertension, tachycardia, emotional lability, cephalalgia, hypotension and cutaneous flushing), which has been observed in some cases of bilateral resection of carotid artery paragangliomas (13). These carotid chemoreceptors are known for their oxygen-sensing capabilities, and they also play an important role in glucoregulation (14). Moreover, it has been demonstrated that intact carotid chemoreceptors are essential for increasing heart rate and maintaining arterial blood pressure during hypoglycaemia in humans, supporting the contribution of the carotid chemoreceptors to blood pressure control (15). In our observation, the patient presented severe arterial hypertension and symptoms of PRES/RCVS several days after the second surgery for CBTs; at that time, we could consider that there was a bilateral resection of the CBT (Figure 2). OPEN IN VIEWER

Even if its occurrence is infrequent, unilateral or bilateral carotid body resection should lead to a systematic neurological survey during the first few days after surgery, a fortiori in case of headaches.

Key findings

Paragangliomas are slow-growing and highly vascular neoplasms that are usually benign.