HIV-1 related ischaemic trochlear nerve palsy.

Abstract

Sirs: Before the era of combination antiretroviral therapy (ART), neuro-ophthalmic complications occurred in 3 to 8 % of HIV-1 infected patients [11]. Isolated cranial nerve palsies were very rare, and among the six trochlear nerve palsies reported in AIDS, only two were unilateral [4] and all were secondary to lymphomas or opportunistic infections [6, 7, 9, 11]. Microvascular oculomotor nerve palsies have not been described, even though thrombosis or stenosis of intracranial vessels seem to be more frequent in HIV-infected patients [1]. We describe a HIV-1 infected man treated with ART who developed an isolated left trochlear nerve palsy consistent with the diagnostic criteria for an ischaemic aetiology [4, 8]. A 37-year-old HIV-1-infected homosexual man (CDC stage A), with an unremarkable past medical history, awoke one morning with vertical binocular diplopia especially in down gaze. He denied any other neurological symptoms, or fever. A Bielschowsky test and a double Maddox rod test confirmed a left trochlear palsy. In primary position at distance, he exhibited a 2 prism diopter left hypertropia that increased to 6 diopters on right gaze, decreased to orthophoria on left gaze, and increased to 3 diopters on down gaze. With right head tilt he was orthophoric, and with left head tilt he had a 5 prism diopter left hypertropia and 2 prism diopter esotropia. The remainder of his ocular, neurological and general examination was normal. The edrophonium test was negative. The patient had been treated for three years with zidovudine, lamivudine and a protease inhibitor (first indinavir, switched for nelfinavir 9 months ago). The CD4+ cell count was 520/mm3 (18.3 % of total lymphocytes). Chest radiograph, haematological and biochemical tests, serum glucose, cholesterol and triglycerids concentration, erythrocyte sedimentation rate, Borrelia burgdorferi assay, syphilis serology, anticardiolipin antibody, antinuclear antibody assay, antithrombin III, protein S and C levels, activated protein C resistance, thyroid function studies, and acetylcholine receptor antibody titre were unrevealing. Repeated magnetic resonance imaging (MRI) of the brain with millimetric slices of the mesencephalon and the IV’s emergence, MR angiography, cervicocephalic vessels duplex ultrasonography, transcranial Doppler sonography, cardiac echography, brainstem evoked potentials were normal. High-resolution CT of orbits ruled out causes of orbital restrictive ophthalmoplegia. Lumbar cerebrospinal fluid was completely normal and PCR for Herpes viruses in cerebrospinal fluid were all negative. HIV–1 viral load was < 50 copies/ml in both serum and CSF. He had small vertical fusion amplitudes and no head tilt was identified by reviewing old photographs, two features that strongly speak against the congenital nature of the trochlear palsy. The absence of head trauma, and the normality of all investigations ruled out all other causes of acquired trochlear nerve palsies, except microvascular ischaemia of the nerve [4, 8]. The normal protein, glucose, absence of pleocytosis, and negative oligoclonal bands in the CSF, and the normality of MRI were strong arguments against the diagnosis of neuritis. Aspirin (300 mg/d) was initiated. His double vision totally resolved within 2 months. No ocular misalignment was further noted in a one-year follow-up. No cases of trochlear nerve palsy were described as a result of HIV infection in the historical and personal review by Richards et al. [8]. Our patient met the diagnostic criteria for microvascular ischaemia of the nerve, i.e : abrupt onset of an isolated mononeuropathy, absence of dorsal midbrain syndrome and of intraparenchymal lesion on MRI, and complete spontaneous resolution within 100 days [4, 8]. Ischaemic oculomotor mononeuropathies are described in patients older than 60 years and are due to microvascular atherosclerotic injury exacerbated principally by hypertension, diabetes mellitus or hypercholesterolaemia [4, 8]. Our patient was younger, and had no relevant vascular risk factors. He was not a heavy smoker. The cerebral microvascularisation is frequently altered in HIV-infected patients and disturbed vasoreactivity contributes to microinfarcts [1]. The histological lesions consist in mural thickening, increased cellularity, and endothelial cell hypertrophy associated with a reduction in luminal diameter [2, 10]. This microvasculopathy is associated with perivascular and intramural HIV-positive cells of macrophage lineage that may play a role in mediating the vascular injury. Yet, these small vessels features resembled those described in non-HIV aging brains’ patients with hypertension and diabetes [2]. Premature atherosclerosis is frequent in HIV-infected patients but of unknown mechanism [3]. Sideeffects of combined antiretroviral LETTER TO THE EDITORS