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The peripheral nervous system is frequently involved in different stages of HIV-1 infection. Cranial neuropathies have already been described in HIV-1 patients, but never in HIV-2 patients. We describe the first case of multiple cranial neuropathy associated with, and presumably due to HIV-2 itself.
A 25 year old heterosexual white man was referred to our hospital for evaluation of a left facial palsy of insidious onset in the previous days. He complained of hoarseness and episodic horizontal diplopia for the previous 2 months. Past medical history was unremarkable except for an episode of hospitalisation at 3 weeks of age, when he underwent several blood transfusions.
Physical examination was normal except for diffuse tonsillar enlargement. Neurological examination disclosed anisocoria RE>LE, horizontal diplopia on left side gaze without clear evidence of oculomotor palsy, hypoesthesia of the left V3 territory, left peripheral facial palsy, left hypoacusia, bilateral decreased gag reflexes, and dysphonia.
Brain MRI (fig 1A, B) showed enlargement and gadolinium enhancement of the intracranial third (bilateral), fifth (right) and intracanalicular seventh and eighth (bilateral) cranial nerves. A diffuse enlargement of nasopharyngeal lymphoid tissue was apparent.
CSF examination revealed 152 mg/dl protein, 60 cells/μl (mainly mononucleated), and intrathecal IgG synthesis (CSF IgG 0.352 g/l; IgG index 0.84), without oligoclonal band, CSF VDRL, microbiological and cultural examinations were negative, and immunophenotyping of CSF lymphocytes excluded B cell monoclonality. Further investigation disclosed a positive Western blot for HIV-2, plasma viraemia by RT-PCR of 785 HIV-2 RNA copies/ml (2.89 log10), 198 CD4+ cells/μl, CD4/CD8 ratio of 0.3, lymphocyte count of 1074 cells/μl. Serological testing for HIV-1 and plasma viraemia (HIV-1 DNA) were negative. A nasopharyngeal lymphoid tissue biopsy revealed chronic inflammation and did not identify any specific agent. An extensive evaluation (including CSF PCR for Mycobacterium tuberculosis; CMV, HSV, EBV and Toxoplasma serologies; chest x ray; serum calcium; antineutrophil cytoplasm antibody; and antinuclear antibodies) ruled out other possible causes of multiple cranial neuropathy.
The patient was started on highly active anti-retroviral therapy (HAART) with zidovudine, lamivudine and indinavir, which gave full clinical recovery within 4 weeks. Three months later, CSF examination revealed only slight elevation of proteins (61 mg/dl), and 1 cell/μl without intrathecal IgG synthesis. Plasma HIV-2 RNA by PCR was below the threshold of detection (<500 copies/ml) and CD4 count was 243 cells/μl. Brain MRI showed only slight gadolinium enhancement of the right III nerve (fig 1C, D). At follow-up, 2 years later, neurological examination was normal.
We describe a previously unrecognised syndrome in HIV-2 infection. This case deserves further attention for additional reasons: transmission of HIV-2, presumed aetiology, and MRI imaging.
In Portugal, African communities represent a significant percentage of the population and previous studies have documented the presence of HIV-2 among both native Portuguese and immigrants, emphasising the possibility of unusually long incubation periods.1 In our case, HIV-2 may have been acquired through blood transfusions more than 20 years ago, as the patient denied other possible ways of transmission (including sojourn in western Africa or sexual contact with people from this area).
Neurological dysfunction in HIV-2 infection has not been comprehensively studied. In HIV-1 infection, the peripheral nervous system can be involved in different ways, at different stages, with different presumed aetiopathogenic mechanisms.2 Cranial neuropathies have been described mostly in association with opportunistic infections and lymphoma. Rare cases without recognised cause have been attributed to HIV-1 itself.3 In this case, the presentation of cranial neuropathy without identified aetiology, in the context of a newly diagnosed infection, suggest that HIV-2 itself may be the offending agent in our patient. Clinical improvement, associated with the reversal of CSF inflammatory characteristics and MRI findings with HAART, highlights this assumption. Of possible relevance to the latter is a case of optic neuropathy as the presenting feature of HIV-1 infection, with recovery associated with HAART.4 However, in our case we cannot exclude the hypothesis of an immune mediated insult to the cranial nerves or a spontaneous recovery coincident with HAART.
MRI was very useful in diagnosis and follow up, showing an impressive cranial nerve gadolinium enhancement that regressed on treatment. To a lesser extent, this finding has been described in HIV-1 patients and seems to be related to the underlying inflammatory process. However, it is not always associated with clinical dysfunction.5
The affinity of the HIV virus for the nervous system and the potential reversibility of associated dysfunction with HAART should be taken into account, especially when dealing with a patient with neurological symptoms of unknown aetiology. In a case of multiple cranial neuropathy, HIV-2 infection should be included in the differential diagnosis.
We thank Dr. José Vale for his helpful comments
Competing interests: none declared