HIV or human immunodeficiency virus causes AIDS or acquired immunodeficiency syndrome. The HIV virus affects every level of the neural axis, by that I mean that the virus affects the brain, the spinal cord, the nerves as well as the muscles. I shall discuss the neurological manifestations associated with HIV infection in this section starting with the brain.
HIV manifestations in the brain: the brain may be affected soon after the patient gets infected with the HIV virus. Research has shown that soon after entering the human body, HIV virus can be found in the brain. Its first manifestation may be in the form of an aseptic meningitis. The patient has characteristic signs and symptoms of a viral meningitis with headache, neck stiffness, photophobia, body aches and myalgias but when the spinal fluid is analysed no organisms are seen, though the cell count in the spinal fluid may be elevated. This attack of aseptic meningitis subsides on its own (no antibiotics are required). All that is needed is bed rest and some hydration. The HIV virus then enters a dormant state in the brain, remaining silent, causing no overt manifestations.
In the later stages of HIV infection (when the virus has multiplied extensively in the body and the patient's viral load is high and CD4 counts are low) the virus again manifests in the brain clinically. Viral load refers to the amount of virus in the body usually expressed as the number of viral copies in the blood. CD4 count refers to the number of CD4 cells present in the blood. The CD4 cells are a group of immune cells, the HIV virus selectively destroys CD4 cells and thus makes a patient immunodeficient and prone to opportunistic infections. Opportunistic infections refers to infections which normally do not occur in a person with an intact immune system, in people who have immunodeficiency these infections are a major cause of morbidity and mortality. A number of these infections have been associated with late stage infection with HIV. These include:
1) CNS toxoplasmosis
2) Cryptococcal meningitis
3) Progressive multifocal leukoencephalopathy (PML)
4) Cytomegalovirus infections (CMV infections)
5) Tubercular infections of the brain--tubercular meningitis and tuberculoma
6) Various fungal meningitis
HIV affects other levels of the neural axis. It involves the spinal cord causing a vacuolar myelopathy causing stiffness and weakness of the legs and bladder/ bowel problems.
It affects the peripheral nerves and can cause painful neuropathies. The neuropathy associated with HIV infection is usually distal, painful and symmetrical. The drugs used to treat HIV infections are quite strong and some of them too have been implicated in causing neuropathies. HIV can also cause a Gullian Barre Syndrome like presentation. This is an acute peripheral inflammatory demyelinating polyneuropathy (AIDP) which at times can prove fatal due to involvement of the respiratory muscles.
HIV can also involve the muscles causing diffuse proximal muscle weakness (HIV myopathy). Some of the antiretroviral drugs have again been implicated in causing a toxic myopathy.
HIV infection can also involve the brain diffusely (by that I mean no focal or mass lesions are found). This diffuse involvement of the brain causes AIDS dementia complex or what is also referred to as HIV encephalopathy. The virus involves the subcortical parts of the brain and causes psychomotor slowing, cognitive deficits and memory problems.
Let us now discuss the above one by one.
1) CNS toxoplasmosis: CNS toxoplasmosis is one of the most common opportunistic infections seen with HIV/AIDS. It is caused by Toxoplasma gondii and usually presents with intracranial space occupying lesions. By that I mean, it causes lesions in the brain that occupy space much like any other mass such as tumor (cancer). The lesions due to Toxoplasma may either be single or multiple in number and clinically may present with a seizure (as they irritate the brain) or if they lie near the motor strip they may present with weakness or numbness on one side of the body. If they are multiple in the brain they may cause encephalopathy (patient is obtunded and poorly responsive). How is the diagnosis secured? The diagnosis of CNS toxoplasmosis is usually quite easy as the lesions are readily seen on either a CT scan of the brain or an MRI. Your doctor may order the test with contrast to see the surrounding edema and to differentiate them from other similar appearing lesions.
As I stated earlier the diagnosis is relatively easy if there are multiple lesions. The problem arises when there is only one lesion. Then CNS toxoplasmosis has to be differentiated from other disease processes which too may present with a solitary intracranial lesion, especially primary CNS lymphoma. It is important that the correct diagnosis be made as the treatments for the two differ widely. So in cases like these, we neurologists may order other tests such as a Thallium SPECT (single photon emission computed tomography) which is a special type of scan able to differentiate between infection (toxoplasmosis) and tumor (CNS lymphoma) or a biopsy of the lesion may be attempted. Biopsy of course is an invasive procedure and hence we try hard to avoid it.
At times we emprically treat the patient for CNS toxoplasmosis (as treatment is relatively simple and free from side-effects). The CT scan is repeated after 2 weeks of therapy, if the size of the lesion has regressed then it implies that we are dealing with CNS toxoplasmosis. If the lesion has not regressed in size after treatment for 2 weeks or has increased in size, then the possibility of it representing a solitary CNS lymphoma increases.
2) Primary CNS lymphoma: primary CNS lymphoma is an aggressive tumor that commonly ocurs in people who are immunocompromised. There is some evidence to show that Epstein Barr (EB) virus may be involved in its causation. It commonly presents as a mass in the brain which lies near the ventricles. Primary CNS lymphoma is a B-cell tumor. It is responsive to radiation therapy and chemotherapy but the prognosis is poor.
3) Cryptococcal meningitis: this is the most common fungal meningitis seen in AIDS patients. It is caused by cryptococcal neoformans. Patients present with typical features of meningits (headache, stiff neck, fatigue and generally not feeling good) but sometimes the signs may be more subtle in HIV patients. Cryptococcal meningits is more commonly seen if the CD 4 counts are low and the viral load is high. Thus if the clincal suspicion is high, your doctor may order a CSF examination (spinal tap) to look for this. Usually this meningitis raises the intracranial pressure and thus patients complain of headaches. Patients who have cryptococcal meningits are treated with anti-fungal drugs like amphotericin B and fluconazole and the treatment is usually prolonged.
4) Progressive multifocal leukoencephalopathy (PML): PML is a disease again mostly seen in patients who are immunocompromised like those with HIV/AIDS and renal transplant recepients on immunosuppressive therapy. It is caused by the JC virus which involves the white matter of the brain and may present with weakness. Your doctor may order an MRI of the brain and test the spinal fluid for the presence of the JC virus. Unfortunately there is no effective treatment for PML. Various drugs have been tried with no sustained response. The best bet is to use effective medications against HIV itself. Once the viral load starts going down and the CD4 count starts increasing the virus may go into a dormant phase by itself.
5) Cytomegalovirus infection of the brain: CMV causes an encephalitis of the brain which can present with seizures. It also commonly involves the eyes causing a retinitis. Treatment is prolonged and involves the use of drugs like gancyclovir and foscarnet effective against the virus. These anti-viral drugs have significant toxicity and thus the treatment needs to be supervised by a physician skilled in their use.
6) HIV encephalopathy or AIDS dementia complex: some patients with advanced HIV infection develop cognitive deficits. They are slow, have psychomotor retardation (walk and act slowly) and have memory problems. This dementia differs from other dementias like Alzheimer's because these patients have no problems with speech and have no apraxias (problems doing a learned task like using a hammer or tieing their shoe laces). Treatment involves effectively treatment the HIV infection with anti-HIV drugs.
As I stated earlier, HIV affects every level of the neural axis. It can involve the spinal cord and patients usually present with a progressive spastic paraparesis (slowly progressive stiffness and weakness of the legs). This condition has been referred to as vacuolar myelopathy. There is no definite treatment for this condition apart from using effective anti-HIV (retroviral) drugs.
HIV can also affect the muscles and patient present with a myopathy. Weakness occurs of the muscles predominantly of the proximal muscle groups. So patients may experience difficulty in getting up from a low lying chair (their quadriceps are weak) or combing their hair (proximal muscles of the shoulder girdle become weak). Myopathy may also occur during the treatment of HIV infection as some of the drugs used to treat HIV namely zidovudine are toxic to the mitochondria of the muscles.
Anti-HIV drugs are also toxic to the nerves and patient may present with a distal symmetrical neuropathy (the distal nerves get involved and patient's have neuropathic signs and symptoms ie numbness and paraesthesias in their hands and feet, pins and needles sensation and so on).
So you can see HIV does affect the brain in multiple ways. A lot of scientist have raised the argument that HIV is a neurotrophic virus (virus which has affinity for the brain). Many HIV/AIDS patient do not know this and I strongly feel that every patient infected with HIV should see a neurologist at some point.
