Abstract
The association of chronic paroxysmal hemicrania with trigeminal neuralgia was recently described and, analogous to the cluster-tic syndrome, was called chronic paroxysmal hemicrania-tic syndrome (1). To date, only eight cases have been previously reported (1–5). Recently, Boes et al. described the two last cases and reviewed the clinical data of all the patients with this association (5). These authors suggested that the term paroxysmal hemicrania-tic syndrome could be used to describe this association, since the component of paroxysmal hemicrania (PH) of the syndrome was episodic in some patients, while it was chronic in others. The new classification of the International Headache Society (IHS) already incorporates the term paroxysmal hemicrania-tic syndrome to describe this association (6). In the present paper we describe a patient with this syndrome who did not respond to indomethacin, but had complete relief of the pain with acetazolamide plus carbamazepine (CBZ).
Case report
A 69-year-old woman was admitted to our hospital because of a 1-week history of head pain. The pain had a usual duration of 10–15 min (range 2 min to 1 h) with a frequency of 6–10 attacks per day, was located in the right supraorbital and temporal region, supplied by the first division of the trigeminal nerve (V1), and was referred as severe and constant with superimposed shock-like, stabbing, extremely severe pain in the same location (V1 distribution) lasting a few seconds several times during the paroxysms. The attacks appeared both throughout the day and also during sleep at night. Pain was associated with nausea and vomiting, photophobia and phonophobia, ipsilateral ptosis and miosis, ocular injection and lacrimation. It was triggered by opening the mouth, eating, talking, smiling, lightly rubbing the right temporal region, or turning the head, and sometimes occurred spontaneously. Between paroxysms the patient was completely asymptomatic and general and neurological examinations were normal. Blood studies including erythrocyte sedimentation rate, thoracic computed tomography scan and magnetic resonance imaging of the brain were normal. At the time of consultation the patient had taken CBZ 200 mg three times a day showing only a slight relief, and therefore this medication had been suppressed. Both high-flow oxygen and subcutaneous sumatriptan 6 mg shortened the duration of the attacks. Treatment with indomethacin up to 100 mg three times a day associated with CBZ 600 mg daily was also ineffective. However, a combination of acetazolamide up to 250 mg three times a day and CBZ 800 mg daily provided absolute relief from the pain. Two months later, the patient continued to be asymptomatic. Then, acetazolamide was progressively withdrawn, the patient having only two new episodes of moderate pain. Five months later, CBZ was also slowly discontinued. The patient remains asymptomatic without treatment after 3 months of follow-up.
Discussion
The patient we describe clearly had two types of head pain occurring simultaneously. The first type of pain has clinical features usually seen in episodic PH, such as severity, localization, duration, frequency, autonomic features, and ability to trigger attacks by rotating the head (7), and would fit new IHS criteria for probable episodic PH (6), due to the absence of response to indomethacin (Table 1). The patient also had a superimposed shock-like pain with clinical features usually seen in trigeminal neuralgia which was consistent with new diagnostic IHS criteria for trigeminal neuralgia. Moreover, treatment with CBZ, used in trigeminal neuralgia, had a beneficial effect on our patient. Attacks were also accompanied of nausea and vomiting, photophobia and phonophobia. These symptoms are not part of the typical clinical picture of PH or of trigeminal neuralgia.
Diagnostic criteria for paroxysmal hemicrania—new International Headache Society classification
In order to rule out incomplete response, indomethacin should be used in a dose of ≥150 mg daily orally or rectally, or >100 mg by injection, but for maintenance smaller doses are often sufficient.
History and physical and neurological examinations do not suggest any of the disorders listed in groups 5–12, or history and/or physical and/or neurological examinations do suggest such a disorder but it is ruled out by appropriate investigations, or such disorder is present but attacks do not occur for the first time in close temporal relationship to the disorder.
PH-tic is a rare combination of PH and trigeminal neuralgia. There are only eight previously reported cases (1–5). Clinical features of the reported cases share some similarities. It has a female preponderance (seven females/two males, including our case). Attacks can always appear concurrently as in our patient, non-concurrently, or both. The PH component is usually episodic at some time (seven of nine patients), and in some cases is triggerable. Moreover, mechanisms triggering the PH component in our patient and in other five reported cases are trigger factors described in trigeminal neuralgia, but not in PH, such as washing the face, eating, brushing the teeth, talking or chewing. In seven of these nine patients each type of pain required specific treatment. Indomethacin relieved both types of pain in only two patients (2, 3).
The differential diagnosis of PH-tic includes the other trigeminal-autonomic cephalalgias, and secondary causes of PH, such as gangliocytoma of the sella turcica, collagen vascular disease, cerebrovascular disease, Pancoast's tumour, frontal lobe tumour, cavernous sinus meningioma, and intracranial hypertension (8). Recently, PH in association with other pathologies has been reviewed. The associated pathologies described are vascular disorders including an aneurysm and arteriovenous malformations, space-occupying processes, inflammatory or infectious diseases, head injury, intracranial hypertension, essential thrombocytaemia, Arnold–Chiari malformation, and a postsurgical lesion (9). Only the first described case of PH-tic was considered to be secondary to periorbital venous vasculitis (1). The remaining PH-tic cases were diagnosed as a primary headache.
Our case constitutes the first probable PH-tic without response to indomethacin. Although the IHS criteria for PH require a response to this drug, some cases without this feature have been published (8). In our patient, only the combination of acetazolamide and CBZ provided a complete resolution of pain. This response should be attributable in some degree to acetazolamide, since CBZ previously given alone in a similar dose did not provide complete pain relief. Acetazolamide, a carbonic anhydrase inhibitor, is used in the treatment of several neurological disorders such as episodic ataxias, paroxysmal dyskinesias, periodic paralysis, myoclonus, hydrocephalus, or raised intracranial pressure (10). It is also employed in the treatment of headache of different aetiologies, including idiopathic intracranial hypertension, benign cough headache, acute mountain sickness, hypnic headache, familial hemiplegic migraine, migraine aura status, and PH (10–15). Its therapeutic effects are poorly understood: it has proved it decreases cerebrospinal fluid (CSF) production and reduces intracranial pressure (ICP). Acetazolamide could block sodium channels induced by metabolic acidosis, or modulate other ion channels in the central nervous system. In fact, the drug has therapeutic effects on some types of epilepsy and channelopathies (13). In addition, acetazolamide causes hypercapnia and acidosis, both producing cerebral vasodilation (10, 13). Interestingly, some aetiologies of headache relieved with acetazolamide including benign cough headache, hypnic headache, and PH are also indomethacin-responsive headaches, and indomethacin shares some mechanisms of action with acetazolamide such as decrease in ICP and CSF production (10).
The relationship between PH and trigeminal neuralgia is not completely understood. The two conditions might occur coincidentally, although clinical data suggest they might share an underlying common pathophysiology. It is possible that abnormalities in PH-tic include impaired inhibitory mechanisms that normally control afferent activity in the trigeminal nucleus, as well as hypothalamic dysfunction (5). Nevertheless, an explanation for the therapeutic effects of acetazolamide in our patient cannot be provided since exact mechanisms of action of the drug and pathogenic mechanisms of PH-tic remain unknown.