Enduring phenotype of episodic status migrainosus in a prospectively identified patient

Abstract

Episodic status migrainosus is a previously described migraine variant where the exclusive phenotype is that of relapsing status migrainosus. The majority of cases have been reported based on retrospective chart review. A prospectively identified case fulfilling previously published criteria for episodic status migrainosus is reported, with an enduring pattern of attacks meeting criteria for status migrainosus over a 35-year period. A family history in a maternal aunt of a similar phenotype was noted. This prospectively identified case further validates the existence of episodic status migrainosus as a novel nosologic entity. The family history in our case suggests the possibility of genetic susceptibility. Perspective regarding a potential temporal continuum between acute migraine, status migrainosus, and new daily persistent headache is described. Status migrainosus may occur both as a complication of migraine and in the pure form of episodic status migrainosus.

Introduction

Status migrainosus is classified as a complication of migraine, in which an attack is unremitting and associated with debilitating pain and/or associated symptoms for 72 h or more. ¹ Analogous to the concepts of menstrually-related migraine and pure menstrual migraine, status migrainosus has also been reported to exist in a pure form characterized by a phenotype of attacks exclusively meeting criteria for status migrainosus. ^{2 –5} Diagnostic criteria for this migraine variant, termed episodic status migrainosus, have been previously proposed. ² With the majority of previously reported cases being retrospectively identified, prospectively characterized cases are important to validate this variant as a novel nosologic entity. Here, I present such a case, also offering additional clinical and pathophysiologic insight.

Case report

A 50-year-old right-handed woman was evaluated for recurrent headaches since the age of 15, previously diagnosed as “cluster migraines.” She reported a very specific pattern of persistent, severe, and disabling migraine headaches which would last for 4 to 8 weeks (average = 6 weeks) in duration. This would occur 4–6 times per year, when she reports being essentially bedridden during these attack periods. In between, she would be completely free of headache. She denied any circannual predominance or identifiable triggers. Beginning around age 45, she began experiencing spontaneous improvements in both attack frequency and duration. Attack frequency declined to 3–4 times per year, and attack duration to 1 to 2 weeks, untreated. Since age 48, she has been headache free. Seven months prior to her consultation, she suffered recurrent injuries to her neck and left shoulder while transferring her obese mother, who she cares for at home. These injuries triggered severe headache, which was most accurately classifiable as ICHD-3 A5.9, persistent headache attributed to other trauma or injury to the head and/or neck. ¹ The phenotypic characteristics were otherwise identical to what she had experienced during her habitual attacks.

In describing her prior headaches, she denied both typical aura and any prodrome, despite detailed questioning. Headaches were described as predominantly left hemicranial and sidelocked during an individual attack. She had experienced right hemicranial attacks as well but never bilateral headache. Headaches were always severe and persistent, with both throbbing and stabbing qualities. She reported associated photophobia (binocular) and osmophobia but not phonophobia. Nausea was always a feature and occasionally vomiting. She could experience ipsilateral eye watering. Prior preventive treatments with topiramate 100 mg daily, divalproex 500 mg twice daily, amitriptyline 25 mg nightly, and nadolol 40 mg daily had been ineffective in preventing her attacks. Acute treatments with naproxen sodium 550 mg, sumatriptan 100 mg, and/or combination butalbital-containing analgesics were reported as being helpful in reducing her pain intensity but generally were not taken during attacks.

Her prior medical history was notable for a history of recurrent gestational diabetes over three pregnancies, a gastric bypass surgery, and both uterine and cervical cancers treated with hysterectomy. She was a never smoker and denied any history of substance use. She was a former classical ballet dancer. Her maternal aunt was her sole family member with a migraine history, notably, reported to also have a similar pattern of episodic status migrainosus.

Prior evaluations had included magnetic resonance imaging and angiography of the head and neck, which were normal. Her neurological examination was normal.

Discussion

The patient described a highly characteristic and remarkably enduring pattern of relapsing status migrainosus over a 35-year history. Importantly, the case was identified and characterized prospectively, and the patient was able to produce diary-recorded accounts of some of these periods. Her pattern of migraines would meet previously proposed criteria for episodic status migrainosus. ² The sidelocked nature of this particular case with autonomic features could suggest the diagnosis of a probable trigeminal autonomic cephalalgia; however, autonomic features have been noted to be uncommon in prior series of this variant. ² The case is further instructive in that it characterizes a natural history of spontaneously improving attack frequency and duration, although even in that setting, attacks continued to fulfill status migrainosus criteria. Finally, although details could not be confirmed, her reported history of a maternal aunt with a similar phenotype implies a possible genetic susceptibility.

Many important questions surround status migrainosus, including widely disparate accounts of epidemiology. In a retrospective study interrogating the 2013 Nationwide Readmissions Database, status migrainosus accounted for 14.4% of 12,448 hospital admissions for migraine. ⁶ Further, the condition is reported to have been seen in practice by 97% of headache providers when surveyed, implying that it is not rare. ⁷ This is in contrast with retrospective data from a French tertiary center, where status migrainosus was only observed in 24 of 8821 patients over an 11-year observation period. ⁸ It is possible that status migrainosus is overrepresented among certain subsets of patients with migraine, such as those with menstrually-related migraine or migraine with aura. ^2,9

I conclude, based on my observations, that status migrainosus may exist both as a complication of migraine and in a pure form, termed episodic status migrainosus. Taking this further, new daily persistent headache (NDPH), which can phenotypically resemble chronic migraine is recognized as an independent disorder. ¹ However, NDPH may also be diagnosed in patients with a history of migraine. ¹⁰ Therefore, it is somewhat arbitrary as to why status migrainosus may be considered a complication of migraine but not NDPH. A temporal continuum may exist, with acute migraine resolving within 72 h, status migrainosus persisting beyond 72 h and NDPH persisting indefinitely. This conceptualization would allow for pathophysiological investigation of what could either be driving attack progression and/or what deficit could be preventing attack offset. This concept could be further validated by prospective characterization of migraine history among those with NDPH, with attention to attack duration and history of status migrainosus.

Clinical implications

Episodic status migrainosus can exist as a stable and enduring phenotype of relapsing attacks of status migrainosus over a 35-year period.

A family history of other relatives with episodic status migrainosus may be present.