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Show Fourth and Sixth Nerve Palsies Due to Herpes Simplex 1 Infection Evangelos Anagnostou, MD, Vasiliki Mouka, MD, Elisabet Kemanetzoglou, MD, Evangelia Kararizou, MD Abstract: Ocular motor cranial nerve palsies of viral etiology are uncommon and, when accompanied by skin lesions, zoster ophthalmicus is the most frequent diag-nosis. We describe the case of a 68-year-old woman who developed fourth and sixth nerve palsies 3 days after appearance of a painful vesicular skin rash on the left side of her forehead. Neuroimaging was normal but polymer-ase chain reaction (PCR) testing of the cerebrospinal fluid was positive for Herpes Simplex 1 and negative for Varicella Zoster. The patient was treated with intravenous acyclovir, and the cranial nerve palsies resolved over 7 weeks. Although the similarity of the cutaneous vesicular eruption in our patient to that seen with zoster might have led to an incorrect diagnosis, acyclovir seems to be safe and effective for both viral etiologies. Journal of Neuro-Ophthalmology 2015;35:57-59 doi: 10.1097/WNO.0000000000000184 © 2014 by North American Neuro-Ophthalmology Society Although a number of viridae families have been labeled as neurotropic and are able to cause meningitis or encephalitis, only a few have been documented to cause cranial nerve infections. These include human immunode-ficiency virus type 1, Cytomegalovirus, Epstein-Barr Virus, herpes simplex virus (HSV) 1 and 2. The Herpes Zoster virus (VZV), Hepatitis C and Hepatitis B virus, human T-cell lymphotropic virus type 1, and West Nile virus (1). Viral causes constitute a rare subgroup of painful ophthalmo-plegia cases (2). Although VZV is a well-described pathogen leading to third, fourth, and sixth nerve palsies, only single case report exists for other viruses (3-7). We are unaware of Herpes simplex virus type 1 (HSV1) being associated with a fourth or sixth nerve palsy. CASE REPORT A 68-year-old woman developed an itchy vesicular rash on her left forehead 5 days before admission. She was pre-scribed topical acyclovir cream, and 3 days later, she complained of horizontal and vertical diplopia. On admis-sion, she had intermittent stabbing headache in the left periorbital area and an erythematous skin rash with 2 clearly discernible vesicles in the dermatomal distribution of the first division of the left trigeminal nerve. Visual acuity, pupillary reactions, slit lamp examination, and ophthalmos-copy were normal. The patient had a marked right head tilt. In primary position, there was a left esotropia of 20 prism diopters and a left hypertropia of 10 prism diopters. There was limited abduction of the right eye, and the remainder of the neurological examination was normal. Magnetic resonance imaging of the brain and orbits was unremarkable. Lumbar puncture revealed 3 lympho-cytes per cubic millimeter, protein of 35 mg/dL (normal: 15-45 mg/dL), and glucose of 70 mg/dL. CSF samples were sent for polymerase chain reaction (PCR) testing for Herpes viruses, and the patient was started on intravenous (IV) acyclovir 10 mg/kg 3 times daily with the preliminary diagnosis of herpes zoster ophthalmicus. Over the next 5 days, the vesicular rash began to resolve. PCR testing was positive for HSV1 DNA and negative for the other herpes viridae (Herpes Zoster, HSV2, Epstein- Barr, and Cytomegalovirus). Repeat PCR testing of the same CSF sample revealed the same results. Twelve days after symptom onset and while the patient was still on intravenous acyclovir, hematologic testing levels showed ele-vated immunoglobulin G (IgG) levels for both HSV1 and HVZ but was negative for IgM antibodies. At that time, the skin lesions were restricted to a small area on the left forehead (Fig. 1), and the head tilt had improved. Eye Department of Neurology, Eginition Hospital, University of Athens, Athens, Greece. The authors report no conflicts of interest. Address correspondence to Evangelos Anagnostou, MD, Depart-ment of Neurology, Eginition Hospital, University of Athens, Vas Sophias Avenue, 74, Athens 11528, Greece; E-mail: granavan@ yahoo.com Anagnostou et al: J Neuro-Ophthalmol 2015; 35: 57-59 57 Clinical Observation Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. movement recordings revealed normal amplitude for the left eye on horizontal leftward saccades but markedly reduced angular velocity (Fig. 2), consistent with left sixth nerve paresis. On discharge from the hospital, the patient com-pleted 14 days of IV acyclovir and reported no residual horizontal or vertical double vision. Head tilt also resolved, and the patient denied any facial pain or dysesthesias. Examination 7 weeks later showed complete recovery of both ocular motor cranial nerve palsies. DISCUSSION Our patient developed ipsilateral fourth and sixth nerve palsies after a short period of periorbital and temporal pain accompanied by a herpetic rash. PCR conducted on a cerebrospinal fluid obtained 3 days after onset of diplopia was positive for HSV1 DNA. Treatment with intravenous acyclovir was initiated and the ocular motor cranial nerve palsies resolved over 7 weeks. Neuropathy of the third, fourth, or sixth nerves due to HSV is rare. There is one report of 2 patients with third nerve palsies with pupillary involvement caused by HSV1 (5). The diagnosis was made by HSV1 antibodies in the CSF detected by ELISA. A fourth nerve palsy has been reported in a patient recovering from HSV1 encephalitis (8). The extent of the lesions near the Sylvian aqueduct and fourth ventricle of this case report also might have caused a skew deviation. The authors do not provide a detailed description of the ocular motor examination. HSV1 has been linked to nonocular motor cranial neuropathies. It has been implicated in the pathogenesis of "idiopathic" peripheral facial nerve palsy (Bell palsy). HSV1 DNA has been detected in endoneural fluids of the facial nerve or the auricular muscle in 9 of 14 patients with idiopathic facial palsy (9). Vestibular neuritis also has been causally linked to a HSV1 infection, although here data are more sparse (10). Despite the rareness of clinical eye movement abnor-malities in HSV1 infections, the presence of HSV1 DNA has been demonstrated in human ocular motor nuclei. Theil et al (11) examined histological sections of 5 human brainstems by means of DNA amplification of oculmotor, trochlear, and abducens nuclei. HSV1 was found in all nuclei. How does a viral pathogen for cutaneous infections such as HSV1 cause a cranial neuropathy? It is believed that after primary infection, the virus gains access to axon endings within the mucocutaneous surface and is transported to the trigeminal ganglion. The viral genome is maintained within the ganglion, which serves as a reservoir for viral nucleic acids. Latent herpetic infection is a lifelong state. Under FIG. 1. Skin rash on the left side of the forehead 12 days after appearance of initial skin changes. FIG. 2. Nine days after onset of diplopia. Recording of leftward saccadic eye movements with the sound (right) eye covered to a LED-target at 15° eccentricity. Two saccades are shown. Solid line: left eye, dotted line: right eye. Upper panel shows eye position, lower panel shows eye velocity. Note the decreased velocity of the left eye that nevertheless lands on target. The right eye moves with increased velocity and overshoots the target according to Hering law (Horizontal eye movements were recorded using an infrared corneal reflection device [IRIS system; Skalar, Delft, the Netherlands], AC/DC converted at 500 Hz with 12-bit resolution and a passband extending from DC to 70 Hz). deg, degree; ms, millisecond. 58 Anagnostou et al: J Neuro-Ophthalmol 2015; 35: 57-59 Clinical Observation Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. certain circumstances, the virus can reactivate and travel to regions innervated by the fifth nerve causing recurrent disease. It remains unclear how the virus travels from the sensory ganglia and sensory axons to motor fibers. In a case of ophthalmoplegia due to herpes zoster, Lavin et al (12) demonstrated with histopathology that inflammation of the ocular motor cranial nerves was located within the cavern-ous sinus, where they are in close proximity to sensory nerves. In our patient, PCR testing of CSF established HSV1 as the cause of the ocular motor cranial neuropathies. PCR has become the gold standard for the diagnosis of HSV1 infections even in the absence of serum IgM antibodies. In part, this is because the rise of IgM antibodies occurs in a narrow time window and shows a lower sensitivity than PCR (13-15). Serum examination in our patient was per-formed 12 days after symptom onset, beyond the optimal detection period for IgM antibodies. REFERENCES 1. Katirji B, Koontz D. Disorders of peripheral nerves. In Daroff RB, Fenichel GM, Jankovic J, Mazziotta JC, eds. Bradley's Neurology in Clinical Practice, 6th edition. Philadelphia, PA: Elsevier Saunders; 2012. 2. Anagnostou E, Kouzi I, Kararizou E. 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Koskiniemi M, Piiparinen H, Rantalaiho T, Eränkö P, Färkkilä M, Räihä K, Salonen EM, Ukkonen P, Vaheri A. Acute central nervous system complications in varicella zoster virus infections. J Clin Virol. 2002;25:293-301. 15. Page J, Taylor J, Tideman RL, Seifert C, Marks C, Cunningham A, Mindel A. Is HSV serology useful for the management of first episode genital herpes? Sex Transm Infect. 2003;79:276-279. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: E. Anagnostou; b. Acquisition of data: E. Anagnostou, V. Mouka, and E. Kemanetzoglou; c. Analysis and interpretation of data: E. Anagnostou, V. Mouka, E. Kemanetzoglou, and E. Kararizou. Category 2: a. Drafting of manuscript: E. Anagnostou and E. Kararizou; b. Revising it for intellectual content: E. Anagnostou, V. Mouka, E. Kemanetzoglou, and E. Kararizou. Category 3: a. Final approval of the completed manuscript: E. Anagnostou, V. Mouka, E. Kemanetzoglou, and E. Kararizou. Anagnostou et al: J Neuro-Ophthalmol 2015; 35: 57-59 59 Clinical Observation Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. |
