**6. HIV-associated myelopathies**

#### **6.1. Introduction**

HIV-associated myelopathies are less frequent manifestations than encephalopathies. The etiologies of HIV myelopathy include mainly infections and neoplasms. Vacuolar myelopathy (VM) is a manifestation of primary HIV infection as is HIV transverse myelitis. Opportunistic infectious etiologies include CMV, HSV1 and 2, VZV, HTLV1, measles, JC virus, tuberculosis (TB), pseudomonas, syphilis, nocardia, cryptococcus, aspergillus, and *Toxoplasma gondii*. Neoplastic myelopathy in HIV occurs with primary CNS lymphoma (PCNSL), metastatic lymphoma, astrocytoma, and plasmacytoma. Vascular myelopathy is described in the context of necrotizing vasculitis and disseminated intravascular coagulation (DIC) [12, 13].

HSV 1 and 2, CMV, and VZV are other viral myelitides associated with HIV infection.

*Toxoplasma gondii* uncommonly causes myelitis in isolation or in conjunction with focal cere-

Neurological Manifestations of HIV

135

http://dx.doi.org/10.5772/intechopen.80054

CSF findings in VM are nonspecific and nondiagnostic (raised protein with lymphocytic pleocytosis). MRI in VM is often normal, but thoracic high signal changes during progression and cord atrophy in the chronic phase may be observed. Increased T2 cord signal, meningeal, and nerve root enhancement have been described in viral or post viral myelitides, in particular with CMV. In TB of the spine vertebral body and intervertebral disc involvement appears as low signal on T1- and high signal on T2-weighted images; irregular endplates and enhancing paraspinal collections have been documented. Lymphoma shows focal areas of low signal on

There is no treatment for VM. Unlike with HAD, VM has not shown to respond to HAART. Vitamin B12 supplementation, although theoretically beneficial, has not shown any effect. Symptomatic treatment of spasticity and sensory symptoms is pragmatically indicated.

CMV spinal cord disease can improve with the use of ganciclovir alone or in combination

Early diagnosis of a *Toxoplasma gondii* myelitis and therapy with sulfadiazine and pyrimeth-

AIDS in pediatric medicine and child health has been recognized and described since the early 1980s after the identification of the virus itself. It is now a leading cause of childhood

Pediatric HIV is mainly acquired through vertical mother-to-child transmission. This occurs either transplacentally during fetal development in utero; peripartum during passage of the fetus through the birth canal; or postnatally from contaminated breast milk. Other routes of

with cidofavir. Herpes simplex myelitis requires high dose intravenous acyclovir.

HTLV-1-associated myelopathy responds temporarily to intravenous corticosteroids.

Co-infection of HIV and HTLV-1 has been reported in HTLV-1 endemic regions.

T1 and high signal on T2 with patchy contrast enhancement.

TB spine responds well to standard treatment.

amine or Bactrim produce a good response.

Primary CNS lymphoma may respond to chemotherapy.

**7. HIV associated CNS disorders: children**

bral lesions.

**6.5. Investigations**

**6.6. Treatment**

**7.1. Introduction**

morbidity and mortality [15].

#### **6.2. Epidemiology**

Myelopathy in HIV/AIDS occurs with a frequency of 5–10%, compared with HAD frequencies of 15–30% and distal sensory polyneuropathy (DSP) frequencies of 15–50%. These are US based data; in the South African Black population the myelopathy frequency is 3% [4]. Little data is available from elsewhere.

In the US, the vacuolar myelopathy accounts for 5–10% of HIV-related neurological disease (or 20–55% of HIV myelopathy). VM accounts for 4% of HIV neurological disease in Japan (clade B), 1% in Brazil (clade B), and 2% in South Africa (clade C) [4].

The commonest cause of myelopathy in HIV in South Africa is TB (18–50%) [4].

#### **6.3. Pathophysiology**

The pathological hallmark of VM is patchy vacuolization, occurring mainly in the thoracic region and predominantly affecting the lateral and dorsal columns. Axonal degeneration is a secondary phenomenon. There is no significant inflammatory infiltrate.

The exact pathogenesis of VM is unknown. HIV-infected macrophages, microglia, and astrocytes secrete myelin toxic immunoactive substances like TNF α, IL 1, and 6. TNF α causes oligodendrocyte and myelin damage via reactive oxygen species. This oxidative stress to oligodendrocyte membranes causes increased consumption of antioxidants (e.g., glutathione) and methyl groups, which are essential in myelin maintenance. In HIV patients with VM, S-adenosylmethionine (SAM), the universal methyl group donor is decreased like in patients with vitamin B12 deficiency, accounting for the striking pathological similarities, namely the vacuolar change. It is postulated that cytokines released by HIV infected macrophages lead, via SAM depletion to a metabolic disorder that causes the white matter vacuolization in VM. Co-occurrence of SAM depletion and macrophage activation in immune suppressed HIV negative individuals (hematological malignancies, organ transplantation) can produce a clinically and pathologically identical myelopathy [12–14].

#### **6.4. Clinical features**

VM clinically manifests as a subacute, gradually progressive dorsolateral thoracic spinal cord syndrome presenting with spastic paraparesis, hyperreflexia, and extensor plantar responses. Sensory ataxia (30%) and a co-existent distal sensory neuropathy (53%) are present while a crisp sensory level is rare (13%). Bladder sphincter disturbance can occur. VM has been observed to co-occur with HAD and DSP as a possible distinctive syndrome [4].

Tuberculosis can cause a transverse myelitis (often longitudinally extensive), spinal meningitis and Pott's disease of the spine leading to cord compression. The latter is characterized by back pain, spinal tenderness and fever are characteristic features. Presentation is with para- or tetraplegia. TB myelopathy is common in endemic areas and is not HIV stage specific [4].

HSV 1 and 2, CMV, and VZV are other viral myelitides associated with HIV infection.

Co-infection of HIV and HTLV-1 has been reported in HTLV-1 endemic regions.

*Toxoplasma gondii* uncommonly causes myelitis in isolation or in conjunction with focal cerebral lesions.

#### **6.5. Investigations**

lymphoma, astrocytoma, and plasmacytoma. Vascular myelopathy is described in the context

Myelopathy in HIV/AIDS occurs with a frequency of 5–10%, compared with HAD frequencies of 15–30% and distal sensory polyneuropathy (DSP) frequencies of 15–50%. These are US based data; in the South African Black population the myelopathy frequency is 3% [4]. Little

In the US, the vacuolar myelopathy accounts for 5–10% of HIV-related neurological disease (or 20–55% of HIV myelopathy). VM accounts for 4% of HIV neurological disease in Japan

The pathological hallmark of VM is patchy vacuolization, occurring mainly in the thoracic region and predominantly affecting the lateral and dorsal columns. Axonal degeneration is a

The exact pathogenesis of VM is unknown. HIV-infected macrophages, microglia, and astrocytes secrete myelin toxic immunoactive substances like TNF α, IL 1, and 6. TNF α causes oligodendrocyte and myelin damage via reactive oxygen species. This oxidative stress to oligodendrocyte membranes causes increased consumption of antioxidants (e.g., glutathione) and methyl groups, which are essential in myelin maintenance. In HIV patients with VM, S-adenosylmethionine (SAM), the universal methyl group donor is decreased like in patients with vitamin B12 deficiency, accounting for the striking pathological similarities, namely the vacuolar change. It is postulated that cytokines released by HIV infected macrophages lead, via SAM depletion to a metabolic disorder that causes the white matter vacuolization in VM. Co-occurrence of SAM depletion and macrophage activation in immune suppressed HIV negative individuals (hematological malignancies, organ transplantation) can produce a

VM clinically manifests as a subacute, gradually progressive dorsolateral thoracic spinal cord syndrome presenting with spastic paraparesis, hyperreflexia, and extensor plantar responses. Sensory ataxia (30%) and a co-existent distal sensory neuropathy (53%) are present while a crisp sensory level is rare (13%). Bladder sphincter disturbance can occur. VM has been

Tuberculosis can cause a transverse myelitis (often longitudinally extensive), spinal meningitis and Pott's disease of the spine leading to cord compression. The latter is characterized by back pain, spinal tenderness and fever are characteristic features. Presentation is with para- or tetraplegia. TB myelopathy is common in endemic areas and is not HIV stage specific [4].

observed to co-occur with HAD and DSP as a possible distinctive syndrome [4].

of necrotizing vasculitis and disseminated intravascular coagulation (DIC) [12, 13].

(clade B), 1% in Brazil (clade B), and 2% in South Africa (clade C) [4].

secondary phenomenon. There is no significant inflammatory infiltrate.

clinically and pathologically identical myelopathy [12–14].

The commonest cause of myelopathy in HIV in South Africa is TB (18–50%) [4].

**6.2. Epidemiology**

134 Advances in HIV and AIDS Control

**6.3. Pathophysiology**

**6.4. Clinical features**

data is available from elsewhere.

CSF findings in VM are nonspecific and nondiagnostic (raised protein with lymphocytic pleocytosis). MRI in VM is often normal, but thoracic high signal changes during progression and cord atrophy in the chronic phase may be observed. Increased T2 cord signal, meningeal, and nerve root enhancement have been described in viral or post viral myelitides, in particular with CMV. In TB of the spine vertebral body and intervertebral disc involvement appears as low signal on T1- and high signal on T2-weighted images; irregular endplates and enhancing paraspinal collections have been documented. Lymphoma shows focal areas of low signal on T1 and high signal on T2 with patchy contrast enhancement.

#### **6.6. Treatment**

There is no treatment for VM. Unlike with HAD, VM has not shown to respond to HAART. Vitamin B12 supplementation, although theoretically beneficial, has not shown any effect. Symptomatic treatment of spasticity and sensory symptoms is pragmatically indicated.

CMV spinal cord disease can improve with the use of ganciclovir alone or in combination with cidofavir. Herpes simplex myelitis requires high dose intravenous acyclovir.

HTLV-1-associated myelopathy responds temporarily to intravenous corticosteroids.

TB spine responds well to standard treatment.

Early diagnosis of a *Toxoplasma gondii* myelitis and therapy with sulfadiazine and pyrimethamine or Bactrim produce a good response.

Primary CNS lymphoma may respond to chemotherapy.
