Abstract
Trigeminal autonomic cephalgia's (TAC’s) are a rare group of headache disorders associated with ipsilateral cranial autonomic dysfunction. Although the majority of cases are believed to occur as a primary disorder, symptomatic cases have been described. We report a case of a patient with multiple sclerosis (MS) and facial pain associated with autonomic dysfunction. The phenomenology and pathophysiology related to this presentation are discussed.
Case report
A 53 year-old man complained of facial pain while attending a routine follow-up appointment regarding secondary progressive MS. MS had been diagnosed 11 years previously on a clinical basis, supported by typical abnormalities on cerebral magnetic resonance imaging (MRI) (Fig. 1) and bilaterally delayed visual evoked responses. Facial pain had been occurring for almost one year. During this time the pain had become increasingly frequent, but its characteristics had remained constant. Each attack commences with pain shooting from his left upper lip to above and medial to his left eye. A number of excruciating stabs occur over a 15 second period, then a piercing pain evolves which affects the medial left cheek in a patch of five centimetres in diameter sparing the nose. This pain is severe and remains constant for approximately 20 s. During this period the left eye becomes markedly injected and lacrimates profusely. There is no ptosis or nasal stuffiness. Attacks have typically occurred 40 times daily in recent weeks, and can be triggered by speaking, eating, brushing the teeth and touching his upper lip. Episodes are never nocturnal and are not influenced by alcohol.
Sagittal MRI (FLAIR) images showing slices through the region of the lateral venticle (a) and the hypothalamus (b).
Cerebral MRI showed periventricular white matter lesions typical of MS. No abnormalities were apparent in the brainstem, hypothalamus or along the course of the trigeminal nerve. Treatment with Carbamazepine and Gabapentin at therapeutic doses proved ineffective. Regular dihydrocodeine offered minimal symptomatic relief. Subsequently, the use of Lamotrigine resulted in complete cessation of attacks within days of commencing treatment at a dose of 25 mg once daily.
Discussion
The label we have given this patient's symptoms is of a secondary TAC on the basis that on a background of MS he has developed pain with features of trigeminal neuralgia (TN) at onset followed by a prolonged pain more in keeping with a TAC. When compared to primary headache syndromes symptomatic headaches are often recognized to have atypical features, however, the purpose of this report is not to suggest a new headache diagnostic category, but to propose that the distinctive characteristics in this case may reflect the underlying pathology of MS.
In the case described the character and distribution of the pain at the beginning of the attacks is most suggestive of TN. There is a recognized association between TN and MS. Hooge and Redekop (1) report the prevalence of TN in MS to be 1.9%, with symptoms occurring an average of 11.8 years after the diagnosis of MS. The aetiology is thought to involve demyelinating lesions affecting trigeminal pathways (2), although alternative causes such as vascular compression of the trigeminal nerve have also been demonstrated in MS (3).
The pain during the later phase of the attacks described has prominent autonomic symptoms typical of a TAC. Of the recognized forms of TAC, the duration and periodicity fits best with the syndrome of ‘Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing’ (SUNCT), first described by Sjaastad et al. in 1989 (4). However, pain in a maxillary distribution and prominent trigger factors are rare in SUNCT. Differentiation between SUNCT and TN can be difficult, and there have been a number of reports of lacrimation associated with TN (5, 6), perhaps most commonly in first division TN (7). TAC's can be symptomatic, for example SUNCT secondary to pituitary tumours (8), but the features occurring in the case described have not previously been reported in association with MS.
The absence of brainstem abnormalities on MRI in our case fails to provide an obvious clinical-radiological correlate to explain the symptomatology. We speculate on an alternative pathophysiological theory. Functional MRI has demonstrated ipsilateral hypothalamic activation during a SUNCT attack (9). Disturbance of temperature regulation, fatigue, hypersomnolence and neuroendocrine dysfunction have all been attributed to hypothalamic involvement in MS. Reversible MRI changes in the hypothalamus have been shown in MS (10), and Huitinga demonstrated features of demyelination in the hypothalamus on histopathological examination in 16 out of 17 patients with MS who came to autopsy, irrespective of the presence of symptoms suggestive of a hypothalamic lesion (11). Despite the lack of overt hypothalamic abnormality on MRI in our case, hypothalamic dysfunction related to a strategically placed MS-associated lesion may be the origin of the symptoms by means of trigemino-vascular and trigeminal-autonomic activation.
The dramatic response to Lamotrigine in our case is complementary to previous reports of its benefit in SUNCT (12, 13). We therefore recommend a trial of Lamotrigine in secondary TAC’s. We wonder whether steroid treatment may also be useful in cases of TAC-like headaches associated with MS. We would be interested in hearing from others with experience of similar facial pain or headaches occurring in association with MS.