Acephalgic Migraine Presenting as Episodic Fatigue and Nausea: A Case Report

Case Presentation

A Caucasian woman, age 38 years, presented to a private internal medicine diagnostic clinic with a year-long history of episodic nausea, profound fatigue, and cognitive dysfunction. These episodes, which varied in frequency but occurred at least once a month, lasted between 24 and 72 hours. During each episode, she experienced nausea that prevented eating, an overwhelming and incapacitating sense of exhaustion, and a diminished ability to concentrate or perform cognitively demanding tasks, especially in her role as a practicing physician. The episodes followed a stereotypical pattern, with abrupt onset of nausea, which gradually built up to the other symptoms and resolved slowly. She reported increased irritability during these episodes, stating she had “little patience.” She also expressed frustration about their recurring nature and impact on her quality of life. She experienced no symptoms or impairment in the period between episodes.

Some of the episodes were accompanied by abdominal bloating and diarrheal transit with no blood or mucus, which had led to a trial of gluten-free diet for suspected celiac disease, without improvement. She reported a few episodes of vertigo in the two preceding years, which had been diagnosed as benign paroxysmal positional vertigo (BPPV) by an ear-nose-and-throat surgeon. She did not report headache, photophobia, or phonophobia. On some occasions, she also experienced a sensation of heaviness in her limbs, though she struggled to describe the exact nature of this phenomenon. The patient denied fever, flushing, hyperdiaphoresis, or vomiting. She had tried metoclopramide for nausea, but only ondansetron exerted any effect. During one episode, a previous physician prescribed a one-week course of prednisolone (20 mg/day). The patient vaguely associated this treatment with a quicker resolution of symptoms and interruption of new episodes of severe nausea for a few weeks, although she maintained paroxysms of fatigue. Other previous treatments had included empirical doxycycline, with no effect.

The patient had been a vegetarian for the last 11 years. Past medical history was relevant for irritable bowel syndrome, autoimmune thyroiditis (with reportedly normal thyroxine levels on recent testing), and prior episodic bouts of depression. She had no history of migraine, epilepsy, or other autoimmune or metabolic disorders. A review of travel history revealed visits to several countries in Europe and Southern Asia, with ingestion of street food. She lived in an urban area with a stable partner and owned a dog, which had recently been treated for a parasitic infection. The household was similarly treated at the time.

Her family history included migraine with aura in her father, who also had irritable bowel syndrome, and irritable bowel syndrome in her sister. She denied tobacco and alcohol use, and had no known allergies.

On assessment, the patient appeared well, with stable vital signs. Physical examination was within normal limits, including unremarkable neurological, cardiopulmonary, and abdominal findings. The body mass index was 20.

The patient had previously sought evaluation from multiple specialists, including a general practitioner, an internist, a gastroenterologist, a neurologist, and an otolaryngologist, due to the persistence and impact of her symptoms. Despite extensive testing, including laboratory studies, imaging, and endoscopic evaluations, no significant abnormalities were identified, and no definitive diagnosis was established. A summary of prior investigations is provided in Table 1. She described growing frustration with the lack of answers, at times wondering whether her symptoms were truly indicative of an underlying medical problem or psychosomatic. This uncertainty contributed to a sense of helplessness and personal distress, further compounding the impact of her condition.

The diagnostic picture was summarized as recurrent, episodic, incapacitating fatigue with nausea. Workup was performed to look for or exclude a broad range of additional possible neurological, metabolic, and autoimmune differentials (Table 1).

Laboratory evaluations were unremarkable. Thyroid function remained normal despite the known autoimmune thyroiditis. Routine clinical biochemistry, including electrolytes, renal and liver function tests, glucose, and vitamin B12 and D levels, was within normal limits. Autoimmune testing, including antinuclear antibodies, anti-double stranded DNA, and antiphospholipid antibodies, was also unremarkable. An evaluation for gastrointestinal disorders, including serologic testing for celiac disease and upper endoscopy, revealed only mild gastritis, with no evidence of malabsorption or inflammatory pathology.

A clinical suspicion of a migraine spectrum disorder emerged based on the episodic pattern, stereotypical recurrence of attacks, and with normal interictal periods. The discussion of family history, including her father’s migraine with aura, helped the patient notice a series of episodes with potential association with sleep loss, curry ingestion, and the immediate pre-menstrual period. There was no definite association with emotional stress, coffee or alcohol intake, or physical activity. The patient repeatedly denied headache, but referred to feeling her “head was heavier” during these attacks. Thus, AM with aura was considered a potential differential. The improvement of nausea with ondansetron and not with metoclopramide that had been noted in the first appointment was considered particularly relevant in this context.

Given this suspicion and following discussion with the patient, a therapeutic trial with a triptan and ondansetron was prescribed, and she was encouraged to record her symptoms prospectively. Taking the medication during the first hour of an episode resulted in marked improvement of symptoms within 3 hours, a stark contrast to the usual 3-day duration. Repeated use of triptans during subsequent episodes resulted in a consistent and rapid resolution of symptoms, strongly supporting the diagnosis of AM.

During the follow-up appointment at 3 months, the patient reported a newfound ability to recognize subtle aura symptoms that had previously gone unnoticed, including mild visual disturbances with “undulating lines”, a sensation of limb heaviness, and transient word-finding difficulties that occurred with some of the episodes, after the start of nausea. With the recognition of migraine as the underlying mechanism, and increased awareness and patient engagement, additional potential triggers were identified, including hormonal fluctuations and dietary factors, allowing for targeted lifestyle modifications. These have mitigated, if not resolved, the frequency of episodes.

While she declined prophylactic medication due to concerns about side effects and pregnancy considerations, she continues to manage her episodes with abortive therapy using triptans. Given the established association between migraine with aura and increased cardiovascular risk,^7–10 she was counseled on appropriate risk factor screening and management, which is also managed by her internist.