HIV-Associated Vacuolar Myelopathy

HIV-associated vacuolar myelopathy is a chronic, progressive myelopathy of the thoracic cord, seen in advanced HIV infection, with vacuolation of the lateral and posterior columns. It causes spastic paraparesis, sensory ataxia and bladder dysfunction.

It was found in up to 55% of patients with AIDS at autopsy before effective treatment, but symptomatic disease occurred in about 5 to 10%. It is now uncommon where antiretroviral therapy is available, and is mostly seen in untreated or late diagnosed patients.

Associations. Low CD4 count (under 200 cells/mm3), high viral load, dementia and other HIV-related conditions.

Course. Progressive over months. Antiretroviral therapy can stabilise the disease, but established deficits often persist.

Pathophysiology.

Vacuolar change in the spinal cord resembles that of B12 deficiency, and is attributed to impaired B12-dependent transmethylation from macrophage activation and cytokine effects.

Direct HIV infection of neurons is not shown, and macrophage activation is thought to mediate the injury.

• Slowly progressive leg weakness, spasticity, gait ataxia and leg stiffness over months.
• Sensory ataxia with loss of vibration and position sense; paraesthesia of the feet.
• Hyperreflexia (or reduced ankle reflexes if neuropathy coexists), extensor plantar responses.
• Urinary urgency, frequency and incontinence; bowel and erectile dysfunction.
• Arm involvement is mild or late.

Red flags.

• Acute or rapid onset, sensory level or radicular pain (compression, cytomegalovirus, herpes or tuberculosis myelitis, lymphoma).
• Fever, headache or cranial nerve palsies.
• Progressive upper limb weakness or respiratory difficulty.

• Diagnosis of exclusion in a patient with advanced HIV infection and a progressive myelopathy.
• MRI of the spine: often normal, or shows thoracic cord atrophy or dorsal column T2 hyperintensity; exclude compression, abscess, lymphoma and other causes.
• Plasma HIV RNA and CD4 count; cerebrospinal fluid analysis (cells, protein, polymerase chain reaction for cytomegalovirus, varicella zoster, herpes simplex and tuberculosis).
• B12, methylmalonic acid, folate, copper, syphilis serology, HTLV-1 antibodies and vitamin E.
• Somatosensory evoked potentials and nerve conduction studies for coexisting neuropathy.

Differential diagnosis. Subacute combined degeneration, HTLV-1 associated myelopathy, neurosyphilis, cytomegalovirus myelitis, tuberculous myelitis, lymphoma, copper deficiency, multiple sclerosis and compressive myelopathy.

• Start or optimise antiretroviral therapy: dolutegravir 50 mg orally once daily (50 mg twice daily with rifampicin or other strong inducers) with tenofovir alafenamide 25 mg and emtricitabine 200 mg orally once daily. Maximum dolutegravir 100 mg daily. Monitor HIV RNA at 4 and 12 weeks then 6 monthly, CD4 count, renal function and liver function. Avoid tenofovir alafenamide when creatinine clearance is under 30 mL/min; separate dolutegravir from antacids, iron and calcium; acceptable in pregnancy with specialist advice.
• Replace B12 if low or borderline: hydroxocobalamin 1 mg intramuscularly on alternate days until there is no further improvement, then 1 mg every 2 months. Maximum 1 mg for each injection. Monitor potassium early in severe anaemia and neurological recovery. Avoid in hypersensitivity to cobalamin; use caution in Leber disease.
• Spasticity: baclofen 5 mg orally three times daily, increased by 5 mg every 3 days to a usual 30 to 75 mg daily. Maximum 100 mg daily. Monitor sedation and weakness; withdraw slowly; reduce dose in renal impairment (creatinine clearance under 50 mL/min).
• Bladder urgency: oxybutynin 5 mg orally two to three times daily, increased to a maximum of 20 mg daily. Review at 4 weeks. Monitor constipation, dry mouth, confusion, retention and post-void residual. Avoid in urinary retention, angle closure glaucoma, myasthenia gravis and gastrointestinal obstruction; use 2.5 mg twice daily in older adults and hepatic impairment; intermittent self-catheterisation if residual volume is high.
• Physiotherapy, gait aids, occupational therapy, falls prevention and bowel programme.
• Neuropathic pain treatment as needed (pregabalin or amitriptyline).

Monitoring. Review at 3 months, then 6 monthly; track gait, spasticity, bladder function and viral load.

Referral and escalation. HIV physician and neurology; urology and rehabilitation.

Special groups. Pregnancy: antiretroviral choice with specialist advice. Older adults: lower oxybutynin doses and watch for confusion.