Eight-and-a-Half Syndrome Secondary to Neurotoxoplasmosis: A Rare Case Report

ABSTRACT

Eight-and-a-half syndrome (EHS) is a neuro-ophthalmological condition characterised by horizontal gaze palsy, internuclear ophthalmoplegia, and ipsilateral facial palsy. Albeit rare, EHS is a well reported condition in the literature, with several reports presenting multiple aetiologies. Infarcts are the cause in more than half the cases. Human immunodeficiency virus (HIV)-related cases are rare, and are probably underreported in low- and middle-income countries. In this report, we describe EHS secondary to neurotoxoplasmosis in a 40-year-old HIV-positive Brazilian man. EHS secondary to neurotoxoplasmosis is a challenging diagnosis, with important differential diagnoses, notably for HIV patients.

Introduction

Neurotoxoplasmosis predominantly affects people living with human immunodeficiency virus (HIV) and is a serious public health issue, especially in low- and middle-income countries. It may cause neuro-ophthalmological conditions; challenging diagnoses that require clinical experience, with imaging correlation being of utmost importance.

A rare neuro-ophthalmological disorder is the eight-and-half syndrome (EHS), characterised by a combination of one-and-a-half-syndrome (conjugate horizontal gaze palsy and internuclear ophthalmoplegia) and ipsilateral cranial nerve VII (facial nerve) palsy.¹ To date, there has only been one report of an HIV patient with EHS secondary to neurotoxoplasmosis in the literature.² Low- and middle-income countries have a high prevalence of HIV-toxoplasmosis co-infection, with high morbidity and mortality.³ Yet HIV-related cases are probably underreported in these countries.³ In this report, we present a further case of EHS secondary to brainstem toxoplasmosis in a HIV-infected man from Brazil and discuss the corresponding literature, focusing on the clinical, imaging, and treatment features.

Case report

A 40-year-old Brazilian man presented to the emergency department with sudden onset diplopia, frontal pulsatile headache, and dizziness. There was no history of trauma. His rapid HIV test was positive, but he was previously unaware of his HIV status, and thus was not on antiretroviral therapy. It was not possible to perform a CD4 count at the time of the initial presentation. He had a left head tilt associated with a left hypertropia. He had a left horizontal gaze palsy (during saccadic/pursuit movements and vestibulo-ocular reflex) and a left internuclear ophthalmoplegia (impaired adduction of the left eye with abducting nystagmus of the right eye), consistent with horizontal one-and-half syndrome. Vertical ocular movements and the accommodation-convergence reflex were normal. In addition, he had a left peripheral facial palsy (Figure 1, online supplemental video). The clinical findings were compatible with EHS.

Figure 1.

Left eight-and-a-half syndrome: peripheral facial palsy (wide left palpebral fissure, absent left nasolabial fold) associated with (A) left internuclear ophthalmoplegia (impaired left adduction), (B) left horizontal gaze palsy (impaired left abduction and right adduction), (C) normal upgaze, and (D) normal downgaze.

T1-weighted contrast-enhanced magnetic resonance imaging (MRI) revealed a ring-enhancing lesion in the left of the pontine tegmentum (floor of the fourth ventricle) (Figure 2A,B). T2-weighted MRI demonstrated perilesional vasogenic oedema in the brainstem and T2*-weighted MRI showed a few hypointense lesions in the basal ganglia, periventricular area, and frontal lobe (Figure 2C). Cerebrospinal fluid (CSF) analysis demonstrated an elevated white blood cell count (12/mm³) and negative microscopic examination, reinforcing an atypical central nervous system (CNS) infection as the primary aetiology. Tuberculosis, syphilis, and cryptococcal serologies were negative. A Toxoplasma gondii IgM antibody test was negative, while the IgG antibody test was positive. Molecular diagnosis for neurotoxoplasmosis was not available at our centre. Based on the presentation of nodular cerebral parenchymal lesions in an HIV patient, the presumptive diagnosis was neurotoxoplasmosis.⁴

Figure 2.

(a) Axial and (b) sagittal T1-weighted contrast-enhanced magnetic resonance imaging(MRI) demonstrating a lesion to the left in the floor of fourth ventricle in the bulbo-pontine transition. (c) Axial T2*-weighted MRI demonstrating few hypointense lesions in the basal ganglia, periventricular area, and frontal lobe.

He was treated with cotrimoxazole (trimethoprim 80 mg/sulfamethoxazole 400 mg), four tablets, every 6 hours, for 1 year as well as antiretroviral (dolutegravir 50 mg/lamivudine 300 mg/tenofovir 300 mg) and antibiotic therapies regularly. One year later, he had a CD4 count of 253 cells/μL and undetectable viral load. Further MRI revealed a significant decrease in size of the pontine lesion, in support of the diagnosis of neurotoxoplasmosis.⁴ After a 2-year follow-up, his facial palsy had improved, but his horizontal gaze abnormalities remained unchanged.

Discussion

EHS is a combination of one-and-a-half-syndrome and an ipsilateral peripheral facial palsy (collicular/fascicular facial palsy) (1½ + 7). Its pathophysiology is explained by a lesion incorporating the facial nucleus/fasciculus, the medial longitudinal fasciculus, and the paramedian pontine reticular formation/abducens nucleus, which is the centre of horizontal gaze control, synchronising horizontal gaze during movements of the eyes and head.^1,5,6 Therefore, the caudal paramedian tegmentum of the pons is the main lesion site which causes EHS. This spectrum may be classified into classic EHS (without accompanied symptoms), EHS variants (with vertical or bilateral gaze palsies), and eight-and-a-half plus syndrome (nine, thirteen-and-a-half, and fifteen-and-a-half syndromes).⁶

First reported in 1998 by Eggenberger,¹ EHS is a well characterised, albeit rare condition in the literature. Cerebrovascular disease (ie, infarction) is the main cause (~63%), followed by demyelinating lesions (ie, multiple sclerosis) (~33%).⁷ Other reported causes are cavernoma and tuberculoma. Rarely reported conditions which cause EHS are lymphoproliferative disorder, metastasis, and toxoplasmosis.⁷

Cerebral toxoplasmosis, or neurotoxoplasmosis, is the most common disease of the CNS in HIV patients.^4,8 It is caused by the passage of the Toxoplasma gondii tachyzoite through the blood-brain barrier and may present as diffuse or focal encephalopathy.⁹ Most commonly, there are multiple toxoplasma granulomas (cystic lesions) in the brain, although other possible locations are the cerebellum, spinal cord, and brainstem.⁴ The brainstem is a very rare site for neurotoxoplasmosis (2.2%), occurring primarily in the midbrain.⁹ Thus, specific syndromes may appear based on the location (eg, Weber’s syndrome in midbrain toxoplasmosis).¹⁰

The occurrence of EHS secondary to neurotoxoplasmosis has been previously reported only once.² Also, there has been no report of neurotoxoplasmosis as the sole cause of one-and-a-half syndrome to date. MRI in our case showed a ring-enhancing lesion slight to the left of the midline in the pons on T1-weighted contrast-enhanced MRI, with perilesional vasogenic oedema on T2-weighted MRI.^2,4,9 There are multiple diagnostic methods for neurotoxoplasmosis, however clinico-radiological diagnosis is usually sufficient, considering the frequent unavailability of molecular diagnosis in low- and middle-income countries and generally unnecessary use of histopathological studies, since brain biopsy may present complications, especially in immunocompromised patients.⁴ CNS tuberculoma, cryptococcosis, and cysticercosis are important differential diagnoses, particularly for HIV patients, presenting with similar clinico-radiological findings.⁹

The first-line therapy for neurotoxoplasmosis is pyrimethamine plus sulphadiazine, although cotrimoxazole is a good alternative, commonly used as the first choice in low- and middle-income countries.⁴ Overall, EHS patients have good outcomes, with partial or complete recovery, usually for vascular- and non-vascular-related EHS, respectively, however approximately half of the reported cases still have some oculomotor sequelae.⁷ Our patient had a moderate clinical response, with improved facial paresis but unchanged horizontal gaze movement.

Conclusion

EHS can present a challenging diagnosis. Although brainstem toxoplasmosis is a rare cause of EHS, clinico-radiological surveillance is necessary for such circumstances, notably for HIV-infected patients, due to the important, but difficult differential diagnoses. There needs to be an increase in reporting of HIV-related conditions (eg, HIV-toxoplasmosis co-infection) in low- and middle-income countries, for a better understanding of the rare presentations of this disease.

Funding Statement

The authors reported there is no funding associated with the work featured in this article.

Declaration of interest statement

No potential conflict of interest was reported by the authors.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/01658107.2022.2043390.