Progressive lumbosacral polyradiculopathy is a well-described complication of late HIV infection and is usually caused by opportunistic infections such as cytomegalovirus (CMV), herpes simplex virus (HSV), varicella zoster virus (VZV), Ebstein-Barr virus (EBV), syphilis, tuberculosis (TB), cryptococcus and, less commonly, lymphoma, paraneoplastic polyradiculopathy, chronic inflammatory demyelinating polyradiculopathy (CIDP), or diffuse infiltrative lymphocytosis (DILS).^1,2,3 Infective aetiologies, lymphoma and paraneoplastic polyradiculopathy are usually subacute and are progressive unless treated.^1,3,4,5,6,7

In 2000, Benatar et al. described four HIV-infected patients who presented with acute or subacute weakness with spontaneous recovery.⁸ Infective and inflammatory aetiologies were excluded. This entity was described as a ‘unique’ clinical entity in the setting of HIV or a ‘variant of Guillain–Barre syndrome (GBS)’.⁸ Since 2000, there were no further documented cases in the literature.

Between 2010 and 2015, we retrospectively identified a similar cohort of 11 HIV-infected patients who presented with a motor lumbosacral radiculopathy. In this article, we add to the current literature regarding this unusual group of patients by describing the clinical presentation, demographic features, electrodiagnostic, radiological, cerebrospinal fluid (CSF) findings and response to therapy.

Patients were identified between 2010 and 2015 in the Department of Neurology at Inkosi Albert Luthuli Central Hospital, which is a 1000-bed tertiary hospital in Durban, KwaZulu-Natal province, South Africa. The Department of Neurology attends approximately 8000 patients per year.

The inclusion criteria for patient selection were as follows: HIV-infected patients older than 18 years with lower motor neuron weakness involving exclusively the lower limbs, normal sensation, preserved sensory nerve action potentials (SNAPs) and lumbosacral root enhancement on magnetic resonance imaging (MRI). Exclusion criteria were as follows: abnormal sensation on clinical examination, upper limb or truncal involvement, upper motor neuron signs, sensory nerve action potential on nerve conduction studies that were less than 70% of normal values, compressive or intra-spinal lesions accounting for the weakness, polyradiculopathies due to infective, malignant or paraneoplastic aetiology, clinical features of DILS or raised creatinine kinase levels with electrophysiological or histological features of a myopathy, and electrolyte abnormalities, for example hypokalaemia accounting for weakness and areflexia.

Data extracted from patient records included clinical findings, laboratory results, electrodiagnostic findings (nerve conduction and needle electromyography), MRI of the thoracolumbar and lumbosacral spine, duration of therapy and response to therapy.

Tests that were conducted to exclude infective or neoplastic causes of a polyradiculopathy included CSF polymerase chain reaction (PCR) for VZV, CMV, HSV, EBV; CSF Ziehl–Neelson (ZN) stain, culture and gene expert for TB; CSF Venereal Disease Research Laboratory (VDRL), fluorescent treponemal antibody absorption (FTA-ABS) for syphilis; CSF cytology for malignancy (lymphoma); CSF cryptoccocal antigen, India ink stain and cryptococcal culture; chest radiograph for pulmonary tuberculosis (TB), CSF cytology, paraneoplastic antibodies and MRI spine for structural and inflammatory and/or infective lesions.

Patients were followed up and scored according to the Modified Rankin Scale (mRS) to assess for relapses and response to therapy at 3-month intervals for 6 months and thereafter 6 monthly up to 18 months.

The 11 patients presented in this article represent an unusual cohort of HIV-infected patients with a subacute motor lumbosacral radiculopathy. Sensory, sphincter function and upper limbs were normal in all patients.

The MRI showed gadolinium enhancement confined to the lumbar ventral roots. In other infective or inflammatory aetiologies, such as syphilis, TB, viral infections or lymphoma, both dorsal and ventral roots are involved, enhancement may be nodular and patchy with coexistent myelitis, intramedullary granulomas, subdural collections or discitis especially in infective aetiologies.^9,10,11

The clinical scenario of symmetrical ascending weakness, areflexia and high CSF protein is suggestive of GBS.^12,13 More recently, the boundaries of GBS have expanded and variations include a paraparetic GBS where the upper limbs and cranial nerves are spared.¹⁴ A further variant is associated with HIV seroconversion.^15,16 These patients typically have a CSF pleocytosis as seen in our cohort, which may reflect HIV viral replication in the CSF space rather than immunological changes that occur with the subacute motor lumbosacral radiculopathy.^17,18 The axonal variant of GBS, associated with a high rate of preceding Campylobacter jejuni infection, may present as a pure motor axonopathy.¹⁹ Our patients may meet some of the criteria for a ‘variant GBS’.¹⁹ Benatar et al. described four patients with similar clinical findings. They described these patients as a possible variant of GBS or a distinct clinical entity.⁸ However, the unusual features include duration of progression, limitation of signs to the lower limbs, CSF pleocytosis and response to corticosteroid therapy, which is known not to be of benefit in GBS.^20,21

The above cohort may therefore be consistent with a proximal motor variant of CIDP involving demyelination of the ventral roots rather than GBS. Evidence for the above includes prolonged or absent F responses with normal DMLs, neurogenic changes in the paraspinals, ventral root gadolinium enhancement on MRI, raised CSF protein and rapid response to corticosteroid therapy with no relapses. Denervation on needle EMG may suggest secondary axonal loss. Moodley et al. described CIDP in the setting of HIV. In that particular cohort of patients, demyelination was distal rather than proximal, patients had sensory and motor symptoms rather than exclusively motor manifestations, and both upper and lower limbs were involved.^22,23

The rapid response to corticosteroid therapy and the predilection for ventral roots may suggest an antibody-mediated process that targets the ventral roots only. The production of these antibodies may be a transient phenomenon during the course of HIV infection as none of the patients relapsed during the 18-month follow-up despite stopping corticosteroid therapy for 6 months or less. We hypothesise that immune reconstitution with ART may have prevented relapses by induction of tolerance, by increasing the number of functional T regulatory cells and hence maintaining remission. Some diseases associated with HIV may recover with immune reconstitution, for example HIV-associated CIDP, HIV-associated motor neuron syndrome or even myasthenia gravis, despite there being insufficient literature to support the above.^22,24 Therefore, variable or unexpected patterns can occur in HIV immune reconstitution, with exacerbation of some diseases and improvement of others.

The wide range of CD4 counts may also support an immune-mediated process, which is independent of the stage of HIV. The high CD4 counts in some patients were not explained by concomitant DILS as the patients had no clinical features of DILS.^1,25

Seven of the 11 patients were on ARTs at 18-month follow-up. However, only three patients started ART at 4 months after presentation. These three patients had recovered prior to commencing ART on corticosteroid therapy alone. By 6 months all patients had recovered. Hence, the recovery was likely induced by corticosteroid therapy as no patients showed spontaneous recovery before corticosteroid therapy. However, it is likely that ART-induced immune reconstitution may have prevented relapses as all patients on ART at 18 months follow-up had CD4 counts above 350 cells/µL.

Since the South African government’s rollout programme in 2017 which commenced all HIV-infected patients on ART at the time of diagnosis irrespective of CD4 counts, we rarely encounter the above group of patients. This further supports an immune basis for the disease which may improve with changes in tolerance.

Limitations of this study include retrospective design, small patient numbers and lack of a control arm.

Studies are required to understand the pathogenesis of this disease in order to identify the possible antigenic targets. This may help refine therapy in HIV-uninfected patients with pure immune-mediated motor polyradiculopathy, for example paraneoplastic and other immune ventral root radiculopathies.^{5,6,7,26,27,28}