Neuro-Ophthalmic Manifestations of Mollaret Meningitis

Mollaret meningitis (MM) refers to benign recurrent aseptic meningitis usually following herpes simplex virus 2 (HSV-2) infection. Neuro-ophthalmic manifestations associated with MM are rarely reported. We present a case of recurrent HSV-2 meningitis with the neuro-ophthalmic presentation of papilledema and sixth nerve palsy. To our knowledge, this is the first such description in the English language ophthalmic literature.

Trainees’ Corner Section Editors: Vivek R. Patel, MD Prem Subramanian, MD, PhD Neuro-Ophthalmic Manifestations of Mollaret Meningitis Benjamin Park, BBA, Shruthi Harish Bindiganavile, MD, Mohammad O. Nakawah, MD, Nita Bhat, MD, Andrew G. Lee, MD Abstract: Mollaret meningitis (MM) refers to benign recurrent aseptic meningitis usually following herpes simplex virus 2 (HSV-2) infection. Neuro-ophthalmic manifestations associated with MM are rarely reported. We present a case of recurrent HSV-2 meningitis with the neuro-ophthalmic presentation of papilledema and sixth nerve palsy. To our knowledge, this is the first such description in the English language ophthalmic literature. Journal of Neuro-Ophthalmology 2021;41:e407–409 doi: 10.1097/WNO.0000000000001152 © 2020 by North American Neuro-Ophthalmology Society M ollaret’s meningitis (MM) or recurrent benign idiopathic lymphocytic meningitis is an uncommon recurrent aseptic meningitis lasting 2–5 days, followed by spontaneous resolution (1,2). The symptoms and signs of MM include nonspecific headache, fever, photophobia, and neck stiffness (1). About one-half experience seizures, hallucinations, diplopia, cranial nerve palsies, or altered consciousness (1,2). MM is more common in young women with a mean age of 35 years. The number of recurrent episodes ranges from 3 to 8. The etiology of most MM was unknown until the development and wider use of the polymerase chain reaction (PCR) technique (3). Since the development of PCR, MM is most frequently caused by herpes simplex virus Type 2 (HSV-2) (1,3–6) McGovern Medical School (BP), Houston, Texas; Department of Ophthalmology (SHB, NB, AGL), Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas; Department of Neurology (MON), Houston Methodist Neurological Institute, Houston Methodist Hospital, Houston, Texas; Departments of Ophthalmology, Neurology, and Neurosurgery (AGL), Weill Cornell Medicine, New York, New York; Department of Ophthalmology (AGL), University of Texas Medical Branch, Galveston, Texas; MD Anderson Cancer Center (AGL), University of Texas, Houston, Texas; and Department of Ophthalmology (AGL), the University of Iowa Hospitals and Clinics, Iowa City, Iowa. The authors report no conflicts of interest. Address correspondence to Andrew G. Lee, MD, Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, 6560 Fannin Street Suite 450, Houston, TX 77030; E-mail: [e-mail] Park et al: J Neuro-Ophthalmol 2021; 41: e407-e409 although some authors reserve the diagnosis of MM for idiopathic, recurrent meningitis (7). HSV-1 is known to cause meningoencephalitis and remain dormant in trigeminal ganglion, whereas HSV-2 remains dormant in the sacral ganglia (4). It has been postulated that HSV-2 from the sacral dorsal root ganglia may cause secondary seeding of the cerebrospinal fluid subarachnoid space and produce recurrent attacks of meningitis (4). However, most patients with MM do not present with skin or genital lesions at the onset of their illness, and furthermore, many do not report previous genital infections (4,6,8). It is not clear why active HSV skin lesions are not seen in all patients, but presumably previous asymptomatic infection is the cause (6). We present a case of recurrent HSV-2 meningitis with the neuro-ophthalmic presentation of papilledema and sixth nerve palsy. To the best of our knowledge, this is the first such description in the English language ophthalmic literature. CASE REPORT A 35-year-old Caucasian woman developed acute intractable headache, fever, neck pain, photophobia, and binocular horizontal diplopia. She had morbid obesity (body mass index of 47.5 kg/m2). Her medical history of previous HSV 2 meningitis, migraines, psoriasis, depression, and gastroesophageal reflux disease. Her surgical history included cesarean section, colonoscopy, and esophagogastroduodenoscopy. The family history was significant for hypothyroidism and colon cancer. Ocular history and social history were unremarkable. At the time of her admission, she had a temperature of 100.8° F and was tachycardic to 108 b$min21. Physical examination was significant for a limited range of motion of her neck because of pain and meningismus-related neck stiffness. Neuro-ophthalmic examination showed visual acuity of 20/25 in the right eye (right eye) and 20/20 in the left eye (left eye). Motility examination showed an incomitant esotropia (ET) of 10 prism diopters worse on gaze to the right with a mild abduction deficit in the right eye consistent e407 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Trainees’ Corner FIG. 1. Extra ocular motility examination with abduction deficit in the right eye. FIG. 2. Automated visual field 24-2 showing superior and inferior arcuate defects in the right eye. with a nonlocalizing sixth nerve palsy (Fig. 1). Slit-lamp examination was normal, and there was no uveitis. Ophthalmoscopy showed grade 2 optic disc edema in both eyes (OU). Automated visual field (HVF) testing was normal in both eyes. Laboratory evaluation revealed a neutrophil predominant leukocytosis and elevated serum lactate levels. Computed tomography (CT) scan of the head was normal. MRI of the brain and orbit with contrast showed an empty sella turcica and prominence of the optic nerve sheath fluid consistent with elevated intracranial hypertension (Fig. 2) (9). Magnetic resonance venography (MRV) was negative. Lumbar puncture confirmed an elevated opening pressure of 41 cm H2O. Cerebrospinal fluid analysis showed 629 white blood cells with 94% lymphocytic predominance with normal CSF glucose and protein. HSV2 was positive on CSF PCR studies. A diagnosis of recurrent MM secondary to HSV-2 meningitis. The patient was started on intravenous acyclovir for a total of 10 days and oral acetazolamide 500 mg twice a day. However, over the next 1 month, her headaches continued to worsen, and her vision loss progressed despite increasing the acetazolamide to 3 g per day. Her vision was now 20/30 in the right eye and 20/20 in the left eye. Pupil examination showed right a relative afferent pupillary defect (RAPD) in the right eye. The right abduction deficit and esotropia persisted. HVF now showed a new superior and inferior arcuate field defect in the right eye but was normal in the left eye (Fig. 2). Repeat CSF analysis was normal, and the HSV PCR was negative. The patient underwent an optic nerve sheath fenestration in the right eye but had persistent headache despite maximal medical therapy and acetazolamide, and a ventriculoperitoneal shunt placement was performed. The patient had stabilization of her vision and resolution of her headache after surgery. DISCUSSION Mollaret’s meningitis (MM) or recurrent, idiopathic benign lymphocytic (aseptic meningitis) is often because of HSV2. Neuro-ophthalmic presentations of MM are likely because of nonlocalizing findings of increased intracranial pressure or direct infectious/inflammatory disease and are probably under-recognized. We reviewed the English language literature and found 2 other case reports that described optic disc edema in MM. The possible mechanisms of optic disc edema in MM include infectious, inflammatory, TABLE 1. Case reports of neuro-ophthalmic presentations in recurrent Mollaret meningitis Authors Barontini et al (10) Acosta et al (11) Matta et al (12) Gadhiya et al (13) Neuro-Ophthalmic Findings Anisocoria, dilation of the ventricles on computed tomography head Papilledema, elevated opening pressure on LP (.55 cm H2O) Sixth nerve palsy Disc edema with normal opening pressure LP, lumbar puncture. e408 Park et al: J Neuro-Ophthalmol 2021; 41: e407-e409 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Trainees’ Corner infiltrative, and increased intracranial pressure–related etiologies. Table 1 shows the neuro-ophthalmic findings reported in other cases of MM (10–13). Although acyclovir is commonly used for treatment of MM, the role of prophylactic acyclovir is controversial (14). Although a few studies showed no recurrences with longterm valacyclovir (15,16), 1 trial with valacyclovir 500 mg twice a day in patients with HSV-2 meningitis showed an increased risk of recurrence in the second year of acyclovir (17). However, only half of these patients had proven recurrent HSV-2 meningitis (14). Patients need to have an expedited approach which could include medical (acetazolamide up to maximally tolerated doses) or surgical management (optic nerve sheath fenestration or ventriculoperitoneal shunt) to be able to salvage vision when papilledema is sight threatening. Although both idiopathic intracranial hypertension and secondary intracranial hypertension from meningitis possible coexisted in this patient, the temporal relationship of the episodes of meningitis preceding her vision loss makes it more likely to be secondary in nature. Ophthalmologists and neurologists should consider managing papilledema independent of the cause once vision is affected, and this is the takeaway from this case report. To the best of our knowledge, this is the first case of MM presenting with papilledema and requiring optic nerve sheath fenestration and VP shunt placement in the ophthalmic literature. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. REFERENCES 1. Shalabi M, Whitley RJ. Recurrent benign lymphocytic meningitis. Clin Infect Dis. 2006;43:1194–1197. 2. Galdi AP. Benign recurrent aseptic meningitis (Mollaret’s meningitis): case report and clinical review. Arch Neurol. 1979;36:657–658. 3. 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