Unilateral headache associated with a pontine infarction

Abstract

Brain stem structures are implicated in the generation of migraine and other types of headache. The patient described herein had chronic left hemicranial headaches associated with a left pontine infarction.

Case report

A 64-year-old right-handed woman first developed strictly left-sided headaches in 2002. The headaches started in the left posterior head and evolved into a left-sided headache involving the neck and the left eye. Her pain was vice-like with pressure and throbbing. Photophobia and nausea accompanied the pain when it was severe. She described it as intolerable and excruciating, producing chronic sleep deprivation and inability to engage in routine activities. She was unable to sleep with the left side of her head on the pillow. It often awakened her at 03.30 and prevented her from resuming sleep. There was no phonophobia, osmophobia, ptosis, lacrimation or conjunctival injection. Physical activity had no effect on her pain and she identified no inciting or trigger factors. The patient never consumed alcohol.

Her headaches were intermittent at first, occurring three to four times weekly, and relieved with ibuprofen. The pain evolved into a chronic daily headache without superimposed exacerbations in 2005. A magnetic resonance imaging (MRI) scan in 2005 showed a pituitary tumour with minimal extension into the left cavernous sinus. It was considered an incidental finding. A subtotal hypophysectomy and postoperative stereotactic radiosurgery on the prolactin-secreting adenoma had no effect on her head pain. A C2 gangionectomy in 2007 rendered the pain worse. Subsequent occipital nerve blocks had no effect.

She was treated by numerous neurologists, pain specialists and neurosurgeons over the years. Previous medical treatments included unsuccessful trials of gabapentin (2400 mg daily), amitriptyline (50 mg daily), verapamil (180 mg daily), propranolol (80 mg daily, long acting), pregabalin (150 mg daily), indomethacin (150 mg daily), mirtazapine, tizanidine, duloxetine, cyclobenzaprine, venlafaxine, valproate, leveteracetam, melatonin, venlafaxine and prednisone. She experienced intolerable side-effects from topirimate and divalproex sodium (500 mg extended release). Symptomatic medication therapies included butalbital, methadone, morphine, hydromorphone, oxycodone and various sleep agents. A diagnosis of medication overuse headache was considered, but a 6-month period abstaining from analgesic usage did not improve her pain. Botulinum toxin injections were considered but denied by her insurance provider.

She had a history of hypertension, treated with lisinopril. The neurological examination was normal. She was hospitalized in 2008 for intravenous dihydroergotamine, which rendered her headache-free in 4 days. However, her headache returned within days of hospital discharge.

An MRI in 2008 revealed a left pontine infarction (Fig. 1). The pituitary gland was normal with no evidence of recurrence or residual tumour. Review of previous neuroimaging confirmed the presence of the infarction in 2005. Small vessel ischaemic changes were present in the subcortical white matter.

Figure 1.

Hyperintensity in the left pons indicating previous infarction.

Discussion

This patient had severe, chronic, side-locked, left hemicranial head pain associated with a left pontine infarction. Although she has some of the clinical features of hemicrania continua, the lack of improvement with several trials of indomethacin, and the favourable response to intravenous dihydroergotamine are more suggestive of migraine. However, the headache characteristics do not meet ICHD-2 criteria for a specific primary headache disorder (1).

A few case reports describe structural brain stem lesions producing migrainous headaches. Three patients with lesions from multiple sclerosis (MS) were reported with intractable headache and other neurological manifestations (2). Their lesions were located in the midline in the region of the periaqueductal grey. One patient with bilateral pain developed left hemiparesis and optic neuritis during the second week of the headache. The second patient had a headache that initially alternated sides and then generalized, associated with a plaque in the dorsal pons (2). The headache was accompanied by right hemiparesis and hemihypesthesia. The third patient experienced a bilateral headache and bilateral internuclear ophthalmoplegia as her first manifestation of MS with a single lesion in the periaqueductal grey (3). A retrospective review of MRI studies in patients with MS showed that a plaque within the midbrain/periaqueductal grey matter conferred a 4-fold increase in migrainous headaches, a 2.5-fold increase in tension-type headaches and a 2.7-fold increase in a combination of migraine and tension-type headaches (4). Correlation with headache laterality was not performed. Other reported structural lesions are vascular malformations in the brain stem causing contralateral migraine-like headaches in one patient (5), and ipsilateral migrainous headaches with subsequent generalization in the other patient (5, 6).

Functional neuroimaging studies implicate the dorsal pons and other brain stem structures in the generation of migraine pain. However, the correlation between the side of headache pain and the lateralization of brain stem activation is inconsistent. Positron emission tomography performed in two subjects with spontaneous migraine, with and without aura, showed areas of left-sided activation and right-sided deactivation in the pons (7). These areas did not correlate with the lateralization of the headache pain. A consistent lateralization pattern of activation in the contralateral pons and midbrain was found in nine patients during a spontaneous right-sided migraine compared with their interictal state (8). Unlike areas of cortical activation, the brain stem activation persisted following relief of all migraine symptoms using sumatriptan. Positron emission tomography imaging in six subjects with glyceryl trinitrate-induced migraine showed a correlation between the side of pontine activation and headache laterality, with ipsilateral activation in subjects with unilateral head pain, and bilateral activation in those with bilateral pain (9).

In conclusion, the pontine lesion is the likely source of the patient's chronic unilateral head pain in this case. Brain stem areas postulated to be involved in the pathogenesis of migraine include the locus coeruleus, the dorsal raphe and the dorsolateral pontine tegmentum. The raphe and dorsolateral pontine tegmentum are also implicated in sleep and sleep arousal; this may provide the anatomical correlate for this patient's nocturnal awakening and inability to return to sleep (10, 11). MRI studies of naturally-occurring lesions and functional neuroimaging studies of migraineurs strongly implicate brain stem structures in the generation of migraine pain. However, the laterality of pain does not consistently correlate with the location of either the lesion or the perfusion changes seen on neuroimaging studies.