Persistent Migrainous Visual Phenomena Might Be Responsive to Lamotrigine

Authors

  • Wei-Ta Chen MD,

    1. From the Neurological Institute, Taipei Veterans General Hospital and the Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan.
    Search for more papers by this author
  • Jong-Ling Fuh MD,

    1. From the Neurological Institute, Taipei Veterans General Hospital and the Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan.
    Search for more papers by this author
  • Shiang-Ru Lu MD,

    1. From the Neurological Institute, Taipei Veterans General Hospital and the Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan.
    Search for more papers by this author
  • Shuu-Jiun Wang MD

    1. From the Neurological Institute, Taipei Veterans General Hospital and the Department of Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan.
    Search for more papers by this author

Address all correspondence to Dr. Shuu-Jiun Wang, Neurological Institute, Taipei Veterans General Hospital, Taipei 11217, Taiwan.

Abstract

Two patients with migraine reported having experienced persistent auralike visual phenomena for months to years. All laboratory investigations were normal except for occipital hypoperfusion on the brain single photon emission computed tomography. After lamotrigine treatment for 2 weeks, they both had a resolution of the visual symptoms. Persistent migrainous visual phenomena are potentially benign and probably a status of spontaneous aura.

Abbreviations:
SPECT

single photon emission computed tomography

Tc 99m HMPAO

technetium Tc 99m hexamethylpropyleneamine oxime

NMDA

N-methyl-d-aspartate

Migraine auras typically last from 4 to 60 minutes.1 Those persisting more than 60 minutes and not exceeding 7 days are referred to as prolonged auras. Sometimes the visual auras of migraine are not fully reversible within 7 days.2 In these patients, neuroimaging studies might reveal migrainous infarction in relevant areas.2 However, Luda et al3 first reported a 65-year-old migraineur who, after a typical migraine attack, developed a visual aura that persisted in the right hemifield for more than 12 months. The brain single photon emission computed tomography (SPECT) revealed hypoperfusion in the left hemisphere. Carbamazepine, diazepam, flunarizine, nimodipine, and citicoline could neither abolish nor reduce the visual symptoms. There were some reports4-6 thereafter (Table 1); only two patients were responsive to divalproex sodium.6 Persistent migrainous visual phenomenon may be a new aura variant or a complication of migraine, but its underlying mechanism is still unknown.

Table 1.—.  Reported Patients With Persistent Migrainous Visual Phenomena*
Source, yNo. of
Patients
Duration of the Visual
Symptoms, mo
Occipital Hypoperfusion
on Brain SPECT
Drug
Responsiveness
  • *

    M indicates male; F, female; SPECT, single photon emission computed tomography; NA, not available.

Luda et al,3 19911F121/1Absent
Liu et al,4 19954M 6F2-603/7Absent
Buchholz and Reich,5 19961M10NAAbsent
Rothrock,6 19972F2-24NADivalproex sodium
Present study2F3-362/2Lamotrigine

Recently, lamotrigine was reported to be possibly effective in the prophylaxis of migraine with aura.7 By blocking voltage-sensitive sodium channels, lamotrigine inhibits neuronal release of glutamate, the suggested neurotransmitter involved in the development of cortical spreading depression.8 In this article, we report two women with migraine who developed persistent visual phenomena for 3 months and 3 years, respectively. After treatment with lamotrigine, they both had a dramatic resolution of the visual symptoms.

CASE HISTORIES

Patient 1.

A 45-year-old woman reported having had a coin-sized white spot with occasional flickering in the left hemifield for 3 months, after an attack of migraine without aura. It persisted, regardless of whether the eyes were open or closed, and rendered her unable to read a newspaper. She had a 9-month history of migraine with aura. Her usual aura consisted of a scintillating scotoma lasting for 5 minutes, sometimes followed by transient visual loss, in the same location as the ongoing visual phenomena. The headache occurred 3 minutes after the aura and was mainly left temporal. She did not take any medication for the headache. Half a year ago, her headache became daily, and most of the headaches occurred independently of any migraine aura. She did not take oral contraceptives. Her family history was unremarkable.

There were no abnormal findings on physical examination. Ophthalmologic examination, including visual acuity, color vision, kinetic perimetry, and indirect ophthalmoscopy, did not reveal any abnormalities. Brain magnetic resonance imaging (MRI), electroencephalography (EEG), and visual evoked potentials (VEPs) were all normal, while the brain SPECT with technetium Tc 99m hexamethylpropyleneamine oxime (Tc 99m HMPAO) disclosed decreased blood perfusion in the right occipital region.

After lamotrigine therapy for 2 weeks, 50 mg daily for the first week and 100 mg daily for the second week, the visual symptoms and the headache became dramatically less frequent. She could read a newspaper again. Two months after treatment, she became free of any visual symptoms or headache, and lamotrigine was discontinued. A follow-up brain SPECT at that time revealed no hypoperfusion. She remained symptom-free at a follow-up evaluation 6 months later.

Patient 2.

A 24-year-old woman complained of numerous stars persistently flickering in her right hemifield for 3 years. The stars were uncolored, kept moving eccentrically, and at times would become confluent to form a light. She remembered these visual symptoms first developed during a migraine attack and never disappeared thereafter. She had suffered from headaches characteristic of migraine as long as she could remember. After aged 4, a brief visual phenomenon, which consisted of numerous bright yellow stars flickering in the same location as the ongoing visual symptoms and lasting for 30 to 60 seconds, complicated most of her headaches. After aged 19, the headache became mild but daily. Most of her daily headaches were associated with a visual aura. She took acetaminophen irregularly for episodic headache. Her past history was unremarkable except for a radiofrequency ablation for paroxysmal supraventricular tachycardia 2 years prior. None of her first-degree relatives had a history of migraine.

At presentation, neurological examination was normal. There was no evidence of major psychiatric disease. She had a normal visual acuity, color vision, kinetic perimetry, and indirect ophthalmoscopy. Brain MRI, VEP, and EEG did not reveal any abnormality, but the brain Tc 99m HMPAO SPECT revealed hypoperfusion over the left occipital region. Treatment with flunarizine, atenolol, and propranolol were in vain. After a 2-week administration of lamotrigine, which started with 50 mg per day and doubled a week later, both her daily headache and the persistent visual phenomenon subsided. A follow-up brain SPECT showed resolution of the occipital hypoperfusion. She did not continue lamotrigine due to a rash, one of the adverse effects of lamotrigine. Instead, the medications were changed to polypharmacy including propranolol 120 mg per day and flunarizine 10 mg at night. Two months after discontinuation of lamotrigine, several stars reappeared episodically, independent of headache, in the right hemifield. Following a careful challenge of lamotrigine starting from 12.5 to 25 mg per day, the intermittent “stars” phenomenon, again, was resolved in a couple of days.

COMMENTS

These two patients experienced persistent auralike visual phenomena, which lasted more than 7 days without evidence of brain infarction. They both had a history of migraine with aura and their headache became daily before the onset of the persistent visual symptoms. All laboratory investigations were negative except for occipital hypoperfusion on the brain SPECT. Lamotrigine successfully relieved the visual symptoms.

The visual aura associated with migraine may result from spreading electrical depression in the occipital cortex.9 To date the pathogenesis of persistent migrainous visual phenomena remains uncertain. However, the “eccentrically moving stars” experienced by patient 2 indicate that persistent migrainous visual phenomena might reflect reverberating waves of spreading depression. Spreading depression involves an autocatalytic cycle leading to the release of glutamate, which, with its action on N-methyl-d-aspartate (NMDA) receptors, further causes the spreading depression.10 Patients with persistent migrainous visual phenomena might have a defective spontaneous recovery from the cycle because of glutamate accumulation or NMDA receptor hypersensitivity. Thus, after lamotrigine therapy which has a down-regulation effect on glutamate, our patients recovered from the autocatalytic cycle, followed by a resolution of the visual symptoms.

Based on this point of view, the occipital hypoperfusion on the SPECT of our patients might have been an epiphenomenon reflecting reduced neuronal activity and metabolism during the reverberating waves of spreading depression. Focal hypoperfusion might not be the true pathogenetic origin, since lamotrigine successfully resolved the visual symptoms in our patients. Absence of brain infarction after a long duration of the visual symptoms also rendered an ischemic origin less likely. Conversely, our findings with SPECT seemed compatible with those of Mathew et al11 with positron emission tomography, both indicating that the occipital cortex is involved in the pathogenesis of persistent visual auras.

Persistent migrainous visual phenomenon is a rare, benign, and reversible complication of migraine with aura. In addition to divalproex sodium, it might also be responsive to lamotrigine.

Acknowledgment:  This study was supported by grants from Veterans General Hospital (VGH) 321.

Ancillary