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 Table of Contents  
Year : 2019  |  Volume : 8  |  Issue : 14  |  Page : 45-53

Neurological manifestation of human immunodeficiency virus/Aids

Department of Medicine, University of Abuja Teaching Hospital, Gwagwalada, Abuja, Nigeria

Date of Submission01-Mar-2019
Date of Acceptance01-Jul-2019
Date of Web Publication04-Oct-2019

Correspondence Address:
Dr. G A Onwuegbuzie
Department of Medicine, University of Abuja Teaching Hospital, Gwagwalada, Abuja
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/nnjcr.nnjcr_20_19

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Neurologic complications occur in human immunodeficiency virus (HIV)-infected patients, but only a few of these complications are directly related to HIV infection of the central nervous system (CNS). The virus can affect virtually every aspect of the central and peripheral nervous system, directly or indirectly with the major target being the immune system, including lymphocytes, microglia, and macrophages. Common neurologic manifestations include meningitis, minor and major cognitive impairment, stroke, seizure, immune-mediated effects and opportunistic infection. Diagnosis usually involves a detailed clinical evaluation, including mini-mental scale, as well as lumbar puncture for serology and culture, nerve conduction studies, electromyogram, and neuroimaging. Treatment is usually targeted at the HIV using highly active antiretroviral therapy (HAART) and specific disease entities. CNS side effects of HAART may be transient, while others may require withdrawal of the antiretroviral drug.

Keywords: Human immunodeficiency virus, nervous system, stroke

How to cite this article:
Onwuegbuzie G A, Reng R S. Neurological manifestation of human immunodeficiency virus/Aids. N Niger J Clin Res 2019;8:45-53

How to cite this URL:
Onwuegbuzie G A, Reng R S. Neurological manifestation of human immunodeficiency virus/Aids. N Niger J Clin Res [serial online] 2019 [cited 2023 Sep 22];8:45-53. Available from: https://www.mdcan-uath.org/text.asp?2019/8/14/45/268529

  Introduction Top

Despite the improvement in the diagnosis and “effective palliative treatment” of AIDS-related disorders, the number of people infected with human immunodeficiency virus (HIV) continues to grow, requiring a greater proportion of limited financial, medical, and human resources.[1] In the first decade of the HIV epidemic, neurological complications occurred in about 40%–70% of people with AIDS and abnormal pathologic findings involving the nervous system were found in >90% at autopsy.[2] A precise diagnosis of neurological complications of HIV/AIDS is critical to the practical management of patients, as this would lead to specific therapy and reduction in morbidity. Clinicians faced with neurologic complications often give up on the patient when further diagnostic and therapeutic modalities remain open and capable of preserving worthwhile life.[3] The aim of the review is to highlight the diagnostic evaluation and treatment of neurologic complications of HIV toward improving the outcome for these patients.

  Epidemiology Top

HIV infection is a global pandemic and has continued to spread at an alarming rate.[4] Worldwide, Africa is the continent most severely affected. According to the estimate from the Joint United Nations Programme on HIV/AIDS, about 36.9 million people were living with HIV/AIDS worldwide, with an estimated 25.7 million in Sub-Saharan Africa by the end of December 2017.[5] Africa is the home to 70% of the adults and 80% of the children living with HIV in the world and has accounted for up to three quarters of the over 20 million HIV/AIDS deaths so far.

Although the epidemiology of neurologic disorders is continually shifting, HIV-associated dementia (HAD) developed in 20%–30% of antiretroviral (ARV)-naive adults and in nearly one-half of the pediatric cases before the era of highly active antiretroviral therapy (HAART).[6] However, conditions more directly related to HIV itself, such as minor cognitive/motor disorder, HAD, and sensory neuropathies, remain a source of considerable morbidity. Before the introduction of potent multidrug ARV therapy (1985–1992), the incidence of the central nervous system (CNS)-related opportunistic infections (OIs), progressive multifocal leukoencephalopathy (PML), and primary CNS lymphoma (PCNSL) was increasing, whereas the incidence of HAD remained stable.[7] With the widespread use of HAART, a decline in the incidence of neurologic manifestation of HIV infection has been noted, attributed in part to the virologic suppression and immune restorative effects of ARVs.[8] The prevalence of common neurologic manifestations is summarized in [Table 1].
Table 1: Prevalence of neurologic manifestations of human immunodeficiency virus

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  Neuropathogenesis of Human Immunodeficiency Virus Infection Top

HIV is neurotropic (infects the nervous system) and neurovirulent (causes disease of the nervous system – neuropathy, myopathy, myelopathy, and dementia) and enters the CNS early in the course of infection.[1] There is evidence of HIV-1 infection found in the cerebrospinal fluid (CSF) of the most asymptomatic-seropositive individuals[19],[20],[21],[22] and has been demonstrated at or close to the time of seroconversion. However, the cellular and molecular basis and underlying mechanisms of HIV neuropathogenesis are extremely complex,[21] and our understanding of neurologic disease as a direct cause of HIV infection is incomplete.[6],[23]

The precise mechanisms by which HIV enters the CNS, infects the cells, and produce symptoms have been previously described.[6],[22],[23],[24],[25],[26],[27],[28],[29],[30],[31] Several models attempt to explain how HIV damages neurons. One model suggests that neurotoxic viral proteins are released in the CNS by HIV-infected microglia and brain macrophages, resulting in neuronal injury or death. Neurotoxic viral components include HIV envelope glycoprotein 160 (gp160) and its cleavage products gp120 and gp41, and HIV regulatory proteins Tat, Nef, and Vpr. The virus invades and infects the CSF early, possibly at the time of seroconversion. Even so, clinical evidence of HIV-mediated neurologic dysfunction typically does not occur until late in the course of infection when there is high viral load and evidence of immunosuppression manifested by a low CD4 lymphocyte count. Immune deficiency caused by HIV renders patients vulnerable to infections by agents (viruses, bacteria, fungi, and parasites) that are of low pathogenicity and virulence in immunologically incompetent individuals. Although neurologic complications occur in HIV-infected patients, few are linked to the direct effect of HIV infection on the CNS. With CD4 depletion and immune dysfunction, there is an increased host susceptibility to neurologic opportunistic diseases and neoplasms.

  Neurological Manifestation of Human Immunodeficiency Virus Infection Top

Some patients remain asymptomatic at the time of seroconversion to HIV-positive status, while others have symptoms similar to mononucleosis (fever, sore throat, lymphadenopathy, myalgia, anorexia, fatigue, headache, and retro-orbital pain), frequently with skin rash. One-third of patients may have HIV-related aseptic meningitis at or around the time of seroconversion. Typically, the opening pressure on lumbar puncture is normal, and CSF findings are those of lymphocytic pleocytosis, elevated protein content, normal glucose content, negative serologic results, and cultures negative for other potential infectious etiologies. HIV antibodies and p24 antigen may be detected in the CSF at this stage.

  Direct Effect of Human Immunodeficiency Virus on Central Nervous System Top


Meningitis is multifactorial in patients with HIV/AIDS. Besides specific pathogens, autoimmune processes and HIV itself have been implicated in the development of HIV-associated meningitis. Aseptic meningitis may be caused by HIV-1 itself. An early form of aseptic, HIV-associated meningitis develops within days to weeks after HIV infection. The appearance of meningitis due to cryptococcosis, coccidioidomycosis, histoplasmosis, or other fungal infections is an AIDS-defining event and occurs typically in patients with very low CD4+ lymphocyte counts.

In general, symptoms and signs typically associated with meningitis are less likely to occur in HIV-seropositive individuals than in the general population. This probably reflects the different organisms involved and the differences in immune responses. The physical examination can reveal malaise, photophobia, headache, nuchal rigidity, fever, and cranial neuropathies. Less common findings are confusion, somnolence, and personality changes. The differential diagnosis of HIV-associated meningitis includes chronic paroxysmal hemicrania, meningococcal meningitis, migraine headache, neurosyphilis, and staphylococcal meningitis. Other problems to be considered include lymphomatous meningitis and bacterial meningitis, which often occurs in conjunction with sepsis. Cytomegalovirus ventriculoencephalitis usually results in a change in mental status that evolves over several weeks and can be misdiagnosed as HAD; CSF reveals elevated protein and mononuclear pleocytosis and normal glucose level.

Minor and major cognitive syndrome

There have been shifts in the nomenclature used to describe HIV-associated neurocognitive disorders which have helped to standardize reports from different regions of the world.[32] The most recent proposed three categories: asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), and HAD. However, the diagnoses of ANI and MND require neuropsychological testing that is more likely to be available in research settings [Table 2].
Table 2: Clinical characteristics of human immunodeficiency virus-associated neurocognitive disorders

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Diagnosis is based on HIV Dementia Scale or International HIV Dementia Scale rapid screening test (useful screening test to identify individuals at risk for HIV dementia. The maximum possible score is 12 points, and a score of ≤10 should be evaluated further for possible dementia). Other diagnoses, including syphilis, Vitamin B12 deficiency, and cryptococcal infection should be excluded by appropriate tests. CSF analysis will show increased concentrations of immune activation markers neopterin, β2- microglobulin, monocyte chemo-attractant protein-1, Interleukin-10 and tumor necrosis factor-α.

The standard of care for HAD remains HAART, preferably with agents with optimal CNS penetration. Zidovudine, nevirapine, indinavir/ritonavir, and dolutegravir have better CNS penetration. Patients with HAD may also benefit from psychotropic medications to target specific symptoms, such as psychomotor slowing, agitation, depression, and psychosis. Such therapies are best administered under the guidance of a psychiatrist with experience in treatment of HIV infection.

Human immunodeficiency virus-associated myelopathy

Myelopathy is present in about 20% of patients with HIV/AIDS.[33],[34] Three main types of spinal cord disease are seen in patients, including vacuolar myelopathy (VM). The second form involves the dorsal columns and presents as a pure sensory ataxia, and the third form is also sensory in nature and presents with paresthesia and dysesthesias of the lower extremities. Other diseases involving the spinal cord in patients with HIV infection include HIV-associated myelitis which can present as transverse myelitis with contrast enhancing intramedullary lesions. Other causes which should be excluded include human T-lymphotropic retroviruses (HTLV)-1 associated myelopathy, syphilitic or tuberculous myelitis, Vitamin-B12 deficiency, cytomegalovirus myeloradiculitis, and herpes zoster virus myelitis.

VM is the myelopathy most commonly associated with HIV. It is a slowly progressive painless spastic paraparesis, with sensory ataxia and neurogenic bladder. It is characterized by prominent vacuolar changes in the ascending and descending tracts that particularly affect the thoracic spinal cord. Onset of clinical features occurs subacutely over weeks to months. Features include bilateral lower extremity stiffness and weakness with variable sensory disturbances, gait unsteadiness, bladder and erectile dysfunction, hyperreflexia and Babinski signs, spastic paraparesis with no definite sensory involvement, loss of proprioception, and vibration sense. Paresthesia or numbness of the limbs, if present, is sometimes difficult to distinguish from symptoms of peripheral neuropathy. Upper extremities are affected late if at all. The diagnosis of VM in the setting of HIV disease is one of exclusion. Investigations to exclude other diagnosis include serum Vitamin B12 and folate levels, venereal disease research laboratory (VDRL) test and HTLV-I/II serologies, imaging of spinal cord (magnetic resonance imaging [MRI], computed tomography [CT] scan, myelogram with contrast), CSF analysis, and somatosensory evoked potential.

There is no definitive treatment for HIV-associated myelopathy. Symptomatic treatment is indicated for patients with spasticity and urinary dysfunction. Baclofen or tizanidine may improve leg spasticity and reduce leg cramps. Painful dysesthesias may be treated with neuropathic pain adjuvants, such as lamotrigine or desipramine.

Human immunodeficiency virus neuropathy

Four types of neuropathy are important to recognize in clinical practice, either because of their high prevalence or their therapeutic implications, or both. They include distal symmetric polyneuropathy (DSP), mononeuropathy multiplex, progressive lumbosacral polyradiculopathy, and chronic inflammatory demyelinating polyneuropathy (CIDP).

DSP is by far the most common neuropathy in HIV disease, with the prevalence of clinically diagnosed DSP at 38%.[35] The incidence and prevalence of DSP increase with the progressive immunosuppression that characterizes HIV infection. Several pathogenetic mechanisms have been proposed including advancing age, nutritional status, chronic disease, low hemoglobin level, HIV itself, neurotoxic cytokines, HIV glycoprotein, and low CD4 counts.[36] Characteristic clinical symptoms of DSP include distal numbness, paresthesias, and dysesthesias generally beginning at the level of the toes and ascending to the feet, ankles, and foreleg. The most important neurological signs are depressed or absent ankle reflexes relative to the knees, increased vibratory thresholds at the toes and ankles, reduced pain and temperature sensation in a stocking and glove distribution, and relatively normal joint position sensation. The clinical syndrome of DSP is a common manifestation of several systemic diseases, including chronic alcoholism, neurotoxicity of therapeutic drugs, uremia, Vitamin B12 deficiency, and diabetes mellitus. These conditions should be excluded. Treatment is directed toward the neuropathic pain. Amitriptyline or gabapentin can be useful, as well as carbamazepine, phenytoin, lamotrigine, and other anticonvulsants.

Mononeuropathy multiplex typically presents as multifocal or asymmetric sensory and motor deficits in the distribution of peripheral nerves or spinal roots. Symptoms develop over weeks to months. Deep tendon reflexes mediated by the affected nerves are diminished or absent, but diffuse areflexia does not occur. Cranial neuropathies may be a presenting feature. Some examples are sensory abnormalities in patchy areas of the trunk and extremities (cutaneous nerve), foot drop (motor nerve), or facial palsy (cranial nerve). It is usually self-limiting and responds well to immunosuppressive therapy, such as corticosteroids, if necessary.

Progressive polyradiculopathy has a strong predilection for the lumbosacral roots. The presenting complaint is difficulty with walking due to leg weakness. Flaccid paraplegia may develop within 1–2 weeks in some patients, while urinary retention and/or constipation may be prominent, suggesting involvement of the lower sacral roots with sphincter disturbance.[37],[38] Back pain and subjective numbness, or paresthesias are common, but sensory deficits are rarely severe. Electrophysiological studies reveal widespread denervation in the lower extremity and lumbar paraspinal muscles on needle electromyography. CSF is characterized by the presence of marked polymorphonuclear pleocytosis, elevated protein, and hypoglycorrhachia. Treatment is with ganciclovir or foscarnet.


New-onset seizures are frequent manifestations of CNS disorders in patients infected with HIV.[39] Seizures are more common in advanced stages of the disease but may develop in HIV-positive patients during the course of their illness in the absence of any identifiable structural or toxic metabolic etiology.[39] If the seizure is focal in onset, there may be an underlying structural brain lesion with neurological signs present and electroencephalogram may show focal discharges. Seizures are generalized in a majority, with an increased risk of status epilepticus due to metabolic abnormalities. Cerebral mass lesions, cryptococcal meningitis, and HIV encephalopathy are common causes of seizures. Brain imaging usually is done after an initial seizure. The use of antiepileptic agents is warranted for recurrent seizures.


Cerebrovascular disease has been recognized in HIV-infected patients, including infectious arteritis, inflammatory vasculitis, aneurismal, and small-vessel arteriopathy. In addition, there is premature atherosclerotic cerebral arteriopathy associated with the HAART-induced metabolic disorders. As a result of the increased life expectancy associated with HAART, HIV patients grow older and are exposed to the combined vascular risk of antiviral-induced metabolic changes and advancing age. HIV/AIDS appears to increase the risk of both ischemic and hemorrhagic stroke.[40] This increased risk is most apparent in the young HIV-infected population, in which other risk factors for stroke are seldom evident. Mechanisms underlying the increased risk include OI meningitides and vasculitis, primary HIV vasculopathy, altered coagulation, and cardioembolic events, although the cause may be multifactorial.

  Immune-Mediated (Autoimmune) Disorders Top

The acquired demyelinating inflammatory polyneuropathy is a heterogeneous group of disorders that are associated with immune-mediated attack on peripheral myelin resulting in clinical weakness, sensory loss, and areflexia. Patients with HIV infection may rarely develop either acute inflammatory demyelinating polyneuropathy (AIDP or Guillain–Barré syndrome) or CIDP.[41]

AIDP is clinically characterized by a rapidly progressive muscle weakness involving two or more extremities, generalized areflexia, with progression <4 weeks. It occasionally produces facial diplegia or respiratory compromise and is sometimes preceded by paresthesias in the feet and legs. Detection of anti-peripheral nerve myelin antibodies, with a rising titer, supports an autoimmune mechanism.

CIDP differs primarily from AIDP in having a slower onset and clinical progression of the syndrome after the first 4–6 weeks. Electrophysiological studies reveal evidence of acquired demyelination (e.g., conduction block) and axonal degeneration, usually more prominent in the chronic form of the disease. CSF contains a lymphocytic pleocytosis (10–50 cell/ml) and an elevation of CSF protein (50–200 mg/dl). Treatment is with either intravenous immune globulin (400 mg/kg/day for 5 days) or plasmapheresis (5–6 exchanges over 2 weeks). Repeated treatment at monthly intervals may be needed to achieve clinical stabilization.

Viral infections can trigger neurologic autoimmune disease and attack many parts of the nervous system. The most common presentations are hemiparesis, aphasia, ataxia, pyramidal signs, cranial nerve deficits (oculomotor and facial), involuntary movements (myoclonus and tremors), and partial seizures. The evolution of the clinical signs will depend on the virus, the age, and the immune status of the patient. In general, the very young and the very old have the most serious clinical manifestations of encephalitis.

Diseases affecting the brain's white matter are mostly demyelinating diseases such as multiple sclerosis, PML, and HIV encephalitis. Acute HIV encephalitis is characterized by diffuse myelin damage and is caused by the direct invasion of neurons by HIV. The demyelination of white matter results in headaches, memory loss, movement disorders, and other sensory disorders. Subsequently, it may cause obtundation and grand mal seizures.

HIV-associated vasculopathy in the cerebral circulation includes different forms of arterial disease occurring with no causative agent other than HIV infection. It includes disease of extracranial large arteries, intracranial medium-sized arteries with or without aneurysm formation, and small-vessel disease. The vasculopathy may be asymptomatic, result in stroke, encephalopathy, cognitive impairment, or nonspecific neurological symptoms.

  Immunosuppression-Related Conditions Top


CNS toxoplasmosis has been the most common cause of intracerebral mass lesion in HIV-infected patients. Although earlier reports described the prevalence of 3%–40%,[42],[43] the incidence has declined dramatically among patients receiving cotrimoxazole prophylaxis, and further declined among patients treated with effective ARV therapy. Most of the cases probably represent reactivation of previously acquired infection and occurs in patients with CD4 counts of <200. Presentation includes hemiparesis or parietal signs such as neglect, denial of illness, visual field cut, and hemisensory loss. Others are confusion, headache, personality change, and generalized or focal seizures.

Serum tests for antitoxoplasma antibodies are almost always positive if brain abscess due to toxoplasmosis is present. CSF examination can be normal or show a mononuclear pleocytosis and elevated protein. CSF antibodies to Toxoplasma are not sensitive for toxoplasma encephalitis. CT scan of the brain usually shows multiple ring-enhancing lesions with predilection for cortex and deep gray matter structures such as the basal ganglia. The cerebellum and brain stem are less commonly involved. MRI [Figure 1] is more sensitive than CT scan and can often be helpful in localizing a lesion most accessible for biopsy.
Figure 1: Brain magnetic resonance imaging showing ring-enhancing lesion in toxoplasmosis (red arrow)

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Initial therapy includes combination of pyrimethamine, sulfadiazine, and leucovorin. The use of leucovorin reduces the likelihood of the hematologic toxicities associated with pyrimethamine therapy. The preferred alternative regimen for patients who are unable to tolerate or who fail to respond to first-line therapy is combination of pyrimethamine, clindamycin, and leucovorin. Acute therapy for toxoplasma encephalitis should be continued for at least 6 weeks if there is clinical and radiologic improvement. Adjunctive corticosteroids (e.g., dexamethasone) should be administered to patients only for the treatment of a mass effect associated with focal lesions or edema.

Cryptococcal meningitis

Cryptococcal meningitis is rare among individuals receiving effective ARV therapy. It usually presents as subacute meningitis.[44],[45],[46] Clinical manifestations can be remarkably benign, with vague malaise or nausea alone, and some patients may have a completely normal physical examination. They may present with headache, fever, altered mental status, nausea, and/or vomiting. Less common symptoms are drowsiness, seizures, transient visual, or visual field abnormalities, cranial neuropathies, incoordination, neck stiffness (meningeal sign is absent in up to 70% of cases), obtundation, hemiparesis, or hemisensory disturbance. Clinicians must maintain a high index of suspicion for cryptococcal disease, particularly in the setting of a new onset of headache.

CSF can be normal or show mononuclear pleocytosis, elevated protein, low glucose, and high opening pressure. India ink staining may reveal fungus, but it is relatively insensitive. Determination of CSF cryptococcal antigen (CRAG) titer is essential. Latex agglutination of CSF for CRAG has a sensitivity of 90%–95%. CT or MRI is usually normal or reveals only atrophy. Occasionally, cryptococcomas occur, particularly in the basal ganglia. Focal meningeal and parenchymal enhancement is seen on MRI.

The recommended treatment is 2-week induction therapy with intravenous amphotericin B plus 5-flucytosine (rather than amphotericin B alone). Other options include fluconazole at 1200 mg daily for induction, followed by 8-week consolidation therapy with fluconazole at 800 mg daily, then a maintenance therapy with fluconazole at 200 mg daily. Fluconazole is discontinued if CD4+ cell count is >200 cells/mm,3 or at least 6 months after starting HAART regimen. Despite successful therapy, relapse occurs in 25%–60% of patients unless long-term maintenance therapy is used.

Tuberculous meningitis

Infection with Mycobacterium tuberculosis is the leading cause of death worldwide among persons infected with HIV. Tuberculous meningitis (TBM) is the most severe form of  Mycobacterium tuberculosis Scientific Name Search fection and carries a high morbidity and mortality. CNS tuberculosis has been described in 10%–20% of patients with HIV-related tuberculosis.[47] Tuberculosis and TBM may occur in HIV-positive patients when immunosuppression is less prominent (i.e., CD4+ counts of up to 250). This risk is increased at more advanced levels of immunosuppression. About 50% present with neurologic signs and symptoms without preceding TB symptoms. More often it may be due to reactivation of latent CNS tuberculosis or dissemination of Mycobacterium tuberculosis to CNS. The clinical feature is nonspecific and has variable symptoms which include fever, headache without focal signs, altered mental status, meningeal signs, and focal deficits. Cough with sputum production may be seen in about 20% of patients.

Diagnosis can be difficult, and differentiation from bacterial meningitis is particularly challenging. The CSF findings include lymphocytic pleocytosis, raised protein, and low CSF to blood glucose ratio. Detection of acid-fast bacilli in CSF is simple but with low sensitivity. Culture of Mycobacterium tuberculosis from the CSF is the gold standard, but it is expensive. Elevated CSF adenosine deaminase and anti-Mycobacterium tuberculosis antibody are common. CT scan may reveal hydrocephalus, focal lesions, and meningeal enhancement. MRI is more sensitive for detecting abnormalities with meningeal enhancement in almost 100% of cases.[48],[49] Chest X-ray abnormality is seen in 50% of cases (pulmonary infiltrates and cavitating lesions).[50],[51] Treatment is with isoniazid 5 mg/kg/day (up to 300 mg/day), rifampicin 10 mg/kg/day (up to 600 mg/day), pyrazinamide 15–30 mg/kg/day (up to 2.5 g/day), and ethambutol 15–25 mg/kg/day (up to 1600 mg/day). The minimum duration of treatment is 6 months. Isoniazid may lead to pyridoxine deficiency and a sensorimotor distal polyneuropathy; hence, pyridoxine 20 mg/day should be added to the regimen. The role of steroids in HIV-positive TBM is unclear. ARV drugs can be commenced from 2 to 8 weeks after starting anti-tuberculous treatment because of immune reconstitution syndrome.


The manifestations vary and are usually divided into early neurosyphilis and late neurosyphilis; however, features are no different from neurosyphilis in non-HIV individuals. It is unclear whether infection with HIV is an independent risk factor for the development of neurosyphilis. Although it has been suggested that neurosyphilis is both more fulminant and more difficult to eradicate in the setting of HIV disease, clinical evidence does not support the theory that HIV alters the natural history of Treponema pallidum infection.[52],[53],[54]

Evaluation of HIV-infected patients with a positive serum treponemal antibody test (FTA-ABS or MHA-TP) meeting diagnostic criteria for late latent syphilis should include lumbar puncture. In the absence of neurologic symptoms or signs, a positive CSF-VDRL in the setting of abnormal spinal fluid establishes the diagnosis of latent neurosyphilis. A negative CSF-VDRL does not exclude the diagnosis. A CSF pleocytosis (usually 10–400 cells/μL) and mildly elevated protein (46–200 mg/dL) with or without a positive CSF-VDRL may be the only findings. Treatment is with aqueous crystalline penicillin G. The only alternative that has been studied is ceftriaxone.

Progressive multifocal leukoencephalopathy

PML is caused by John Cunningham (JC) virus, which is human polyomavirus (formerly known as papovavirus). It affects approximately 5%–10% of patients with advanced HIV disease, even though 50% of the general adult populations have antibodies to JC virus.[55],[56],[57] PML is a subacute or chronic progressive illness most often characterized by focal neurologic findings, such as hemiparesis, gait abnormalities, and visual field cuts, as well as changes in mental status and personality. Dementia, encephalopathy, and coma can occur with fulminant disease, as well as seizures.[58]

Diagnosis is by CSF polymerase chain reaction detection of JC virus DNA. MRI typically reveals multiple, nonenhancing subcortical white matter lesions that may coalesce and have a predilection for the occipital and parietal lobes. The lesions show signal hyperintensity on T2-weighted images and diminished signal on T1-weighted images. There is no specific treatment for PML other than the restoration of the immune system.

Primary central nervous system lymphoma

HIV-associated CNS lymphoma is a diffuse, large-cell non-Hodgkin lymphoma, typically of B-cell origin. Affected patients exhibit evidence of Epstein–Barr virus infection, which chronically activates the B-cells thought to be responsible for lymphoma development. In advanced HIV disease, PCNSL is a common cause of cerebral mass lesions.[59] They present with confusion, lethargy, and personality changes, usually with focal deficits such as hemiparesis, hemisensory loss, ataxia, aphasia, and seizure. On CT or MRI, lesions can be single or multiple, and typically enhance, either diffusely or in a ring pattern. The most common locations are the periventricular white matter and deep gray matter, with associated perilesional edema and mass effect. Definitive diagnosis requires brain biopsy or positive CSF cytology. The tumor is radiosensitive. ARV therapy and whole-brain radiation prolong survival and are the mainstay of treatment, but the recurrence rate is high.[60]

  Central Nervous System Medication Effect Top

The use of HAART for HIV infection has brought many features of HIV disease under control but may produce CNS side effects. The common CNS effects of HIV medications are summarized in [Table 3].
Table 3: Common central nervous system effects of human immunodeficiency virus medications

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  Conclusion Top

HIV is a treatable condition, and the physician should be alert to its varied neurological manifestations at all stages of the disease. Clinicians of all specialties must be able to recognize late complications in patients who have had no access to therapy or were never aware of their HIV infection. While treating HIV, it is important to be aware of potential neurologic side effects of ARV drugs, to ensure prompt recognition and management.[63]

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  [Figure 1]

  [Table 1], [Table 2], [Table 3]


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