VZV myelitis with secondary HIV CSF escape

Background

Varicella zoster virus (VZV) may rarely spread to the central nervous system (CNS), causing viral myelitis, most commonly affecting immunocompromised patients.1 2 Paraparesis with sensory-level impairment is common in VZV transverse myelitis, and typically occurs 1–3 weeks following development of the rash.3 However, cases of VZV myelitis occurring without the rash and up to 5 months following the rash have been reported.4 Though not always abnormal, patients with VZV myelitis often present with signs of neuroinflammation, including elevated opening pressure, pleocytosis and elevated protein.3 VZV is often detected by PCR in the cerebrospinal fluid (CSF).

In people with HIV, HIV RNA may be detected in CSF. When HIV RNA in CSF is detectable in the setting of plasma HIV RNA levels <50 copies/mL, or when HIV RNA in CSF is >1 log higher than HIV RNA level in plasma, this is termed CSF ‘escape’.5 When CSF escape occurs in association with a non-HIV CNS infection, such as VZV myelitis, it is classified as ‘secondary’ CSF escape.5 CSF escape is associated with a variety of neurological symptoms, including impairment in cognition as well as motor and sensory function.

Case presentation

A 52-year-old black woman with a history of HIV-1 infection presented with a 5-day history of widespread painful vesicular skin lesions primarily concentrated on the right arm and hand, with lesions also present on the shoulder, nose, breast, back, groin and abdomen. Her medical history included HIV infection diagnosed almost 15 years earlier; 1 month prior to presentation, the CD4 T lymphocyte count was 703 cells/mL and the HIV RNA viral load was 16 600 copies/mL. The patient had a history of intermittent non-adherence to antiretrviral therapy (ART) for 6 months prior to this presentation, reportedly due to lack of adequate food source to take with her new ART regimen of elvitegravir/cobicistat/emtricitabine/tenofovir DF. She had a remote history of cytomegalovirus (CMV) retinitis, herpes simplex virus-1 (HSV-1), genital trichomonas and chlamydia, latent tuberculosis, dermatomal herpes zoster, history of prior cocaine abuse, depression and chronic back pain. She had no recent ill contacts or travel.

On admission, the patient appeared anxious, but vital signs were within normal range. A vesicular rash with erythematous base, which was painful with associated burning and tingling, was observed, predominantly confined to the right arm and hand in a primarily C5–C7 dermatomal distribution (figure 1). Two vesicles were noted on the abdomen, one crossing the midline. A possible lesion on the nose and several lesions on either side of the midline on the abdomen and left breast were seen. A rash was also seen on the back of the head and axilla. Right upper extremity strength was limited due to pain. Other aspects of the physical examination, including cardiopulmonary and neurological examination, were unremarkable. She was started on intravenous acyclovir while awaiting confirmatory direct fluorescent antibody (DFA) testing of a skin lesion swab for VZV and HSV-1, and her outpatient ART was resumed. DFA testing of the skin lesion was positive for VZV and negative for HSV-1 and 2.

On hospital day 3, she developed profound right upper extremity weakness and could not raise her right arm against gravity, along with weakened neck flexion and extension. On neurological examination, her mental status examination was normal, including normal orientation, comprehension, speech, following commands, naming, repetition, attention and recall. She had a left ptosis and sluggish left pupil. She had weakness in the right upper extremity with 2–3/5 power proximally (biceps and deltoid) and 4/5 power distally at the triceps, wrist and finger flexors. Hip flexion and extension were 4+/5 bilaterally. Power was otherwise 5/5 throughout. The plantar response was extensor on the left. Sensation was intact. The remainder of the examination was normal.

Investigations

Her initial baseline laboratory data were significant for white blood cells (WBC) 5.0×10⁹/L (reference range (ref) 4.0–10. 0) and haematocrit 44.4% (ref 37.0–47.0). Serum glucose was 106 mg/dL (ref 70–100), blood, urea, nitrogen (BUN) 22 mg/dL (ref 7–20), BUN/creatinine ratio 36.7 (ref 10.0–20.0) and chloride 95 mmol/L (ref 96–106); other routine laboratory studies were normal. CD4 T cell count was 132 cells/μL (ref 417–1612), plasma HIV viral load was 53 copies/mL and VZV DFA was positive.

MRI of the brain and cervical spine was conducted on hospital day 4 after the onset of right hemiparesis, which revealed abnormal hyperintense T2 signal from C2 to C6 with mild cord expansion, which was slightly asymmetrical, involving more of the right hemicord (figure 2). This lesion was associated with nodular and linear enhancement in the posterior and ventral aspects of the spinal cord. On brain MRI, symmetrical abnormal hyperintense T2 and fluid-attenuated inversion recovery signal was observed within the anterior and medial temporal lobes, with minimal hyperintense signal in the periventricular and subcortical cerebral white matter (figure 3).

A lumbar puncture was performed on day 4 of hospitalisation; the opening pressure was 27 cmH₂O (ref 6–25). Examination of the CSF revealed significant pleocytosis of 82 WBC per microliter (ref 0–5) with 2% neutrophils and 93% lymphocytes, glucose 50 mg/dL (ref 40–70), and protein 110 mg/dL (ref <50). CSF CMV, HSV, Epstein-Barr virus and John Cunningham virus PCR were negative. CSF Gram stain, bacterial and fungal cultures were negative. The venereal disease research laboratory test in the CSF was non-reactive, and the cryptococcal antigen test was also negative. VZV PCR was positive in the CSF. The HIV CSF viral load was found to be 1030 copies/mL. Plasma HIV viral load measured on the following day was 53 copies/mL.

Treatment

Intravenous acyclovir was continued, and intravenous dexamethasone was started due to suspicion for VZV myelitis and possible temporal lobe encephalitis. Over the next 4 days, her right upper extremity and bilateral lower extremity strength improved, and the vesicles began coalescing and crusting.

On day 8 of the hospitalisation, a repeat brain MRI showed stable to minimally improved signal abnormality involving the medial temporal lobes, inferior frontal lobes, as well as subinsular and periatrial white matter. Cervical spine MRI demonstrated mild improvement in the intramedullary signal abnormality in the spinal cord extending from C2 through C5–C6.

She was discharged on day 9 on intravenous acyclovir and oral dexamethasone. At discharge, motor strength was modestly improved: right deltoid 2/5, right biceps 2/5, right triceps 4+/5, right wrist flexion 4+/5, right wrist extension 4/5 and right hand grip 4+/5. Left arm, all 5/5. Sensation was intact.

Outcome and follow-up

The patient completed a total of 4 weeks of intravenous acyclovir followed by 2 weeks of oral famciclovir and then 4 weeks of valacyclovir, for a total of 10 weeks of antiviral therapy. Strength continued to improve except for persistent right deltoid weakness. Three months after the initial admission, CD4 T cell count was 748, plasma viral load was 87 copies/mL and lumbar puncture showed mild lymphocytic-predominant pleocytosis (23 WBC/µL, 100% lymphocytes), CSF HIV viral load of 22 copies/mL and undetectable VZV by PCR. Valacyclovir was discontinued. An electromyography and nerve conduction study performed at 5 months showed right C5 radiculopathy, likely due to residual injury from VZV myelitis. At 6 months, strength was 3/5 in the right deltoid and 4+/5 in the right biceps, but otherwise full strength. She had no sensory deficits. The area of the rash on her upper right arm remained painful, and she also had intermittent numbness and tingling in the fingers of her right hand, consistent with postviral neuropathy. An MRI of the cervical spine 7 months after presentation showed resolution of the meningeal enhancement and cervical cord signal abnormality.