LAUSR

Patients with HIV infection may show various neurologic complications from immunologic derangements [1]. These include Guillain-Barré syndrome (GBS) and Fisher syndrome (FS) that may be a manifestation of immune reconstitution inflammatory syndrome (IRIS) [2,3]. IRIS refers to clinical deterioration after a highly active antiretroviral therapy (HAART) due to restoration of inflammatory immune responses against either infectious or noninfectious antigens [4]. FS is characterized by ophthalmoplegia, ataxia and areflexia [5], and is strongly associated with increased serum antibodies against GQ1b ganglioside [2]. We for the first time report fluctuating vertigo, nystagmus and ataxia without ophthalmoplegia in association with increased serum anti-GQ1b antibody in HIV infection (Fig. 1A). (See Fig. 1.) A 46-year-old man with HIV infection for 10 years developed acute vertigo and vertical diplopia (Fig. 1A). He had been on HAART for four years. The treatment regimen initially included efavirenz 600 mg and abacavir/lamivudine 600/300 mg a day, and had been changed to efavirenz 600 mg and emtricitabine/tenofovir 200/300 mg per day seven months before the presentation. On admission, he showed right hypertropia without a head tilt. Pupillary responses and extraocular movements were normal. He showed right beating spontaneous nystagmus without visual fixation while sitting, and upbeat nystagmus while lying down, head hanging, and Dix-Hallpike maneuver to either side. Bedside head impulse tests were positive for all semicircular canals on the left side (Fig. 1B). Romberg test was negative, but he fell to the left during attempted tandem gait. Other findings of neurological examination were normal. Laboratory evaluation showed a stable control of HIV infection with an absolute CD4 count at 1053/μL (normal range: 480–1580) and CD8 at 1160/μL (210−1030). The viral load was< 40 copies/mL. CSF examination showed a mild pleocytosis (9 WBCs/mm) and increased protein at 73.7 mg/dL. Polymerase chain reactions (PCR) of the cerebrospinal fluid (CSF) were negative for cytomegalovirus, herpes simplex virus, and varicella zoster virus. CSF culture was also negative. Serum IgG antibody for toxoplasma gondii was increased at 117.8 IU/mL (normal:< 2.0), but with a normal IgM titer, which had been first detected 10 years before (IgG titer: 211 IU/mL). Serum IgG and IgM antibodies to GQ1b-ganglioside were markedly elevated with the titers of> 100:1 (normal< 30:1). Anti-GM1 and GD1b antibodies were negative. Antibodies for Ga1NAc-GD1a were not measured. Fundus photography showed leftward cyclotorsion (Fig. 1C). Nerve conduction studies, and brain MRI and MR angiography with gadolinium were normal. The dizziness markedly improved over the following several days and he was discharged with a diagnosis of improving FS. Fourteen days after the discharge, however, the patient revisited the hospital due to aggravated dizziness with oscillopsia and gait disturbance (Fig. 1A). Examination showed spontaneous nystagmus beating to the left and upward. He also showed horizontal GEN and upbeat nystagmus during upward gaze. Bedside and video head impulse tests were positive for both horizontal canals and left vertical canals (Fig. 1D). Deep tendon reflexes were normoactive in four extremities. The gait was ataxic, but limb ataxia was not observed. Again, extraocular movements were normal without a limitation. Follow-up evaluation of the CSF was unrevealing. He also showed complete left caloric paralysis (Fig. 1E). Pure tone and speech audiometry was normal. Cervical vestibular-evoked myogenic potentials (VEMPs) were symmetric, but ocular VEMPs showed no wave formation during stimulation of the left ear. Four days after admission, spontaneous nystagmus and vertical diplopia improved spontaneously (Fig. 1A). However, two days later he reported pain and allodynia on the dorsum of right foot and aggravation of vertical diplopia. Given the deterioration of the symptoms and signs, intravenous immunoglobulin (IVIG), 400 mg/kg, was administered for five days, which resulted in marked improvement of the nystagmus and other symptoms and signs. Serum anti GQ1b antibody became negative 2 months after the symptom onset. Our patient on HAART due to HIV infection developed vertigo, nystagmus and ataxia in association with markedly increased anti-GQ1b antibody. In the mid-1990s, IRIS began to be recognized in patients with AIDS [6]. It is assumed that HAART restores pathogen-specific immunity and induces responses against the tissue antigens. While opportunistic infections associated with IRIS are common in AIDS patients on HAART [1,3,7,8], nystagmus and ataxia associated with elevated anti-GQ1b antibody has not been described. The clinical features of vertigo, nystagmus, and ataxia without ophthalmoplegia are atypical for FS. A previous study described ataxia and ocular