Neurosurgical Management of HIV-Related Focal Brain Lesions

Introduction

Some aspects of epidemiology in the HIV pandemic, according to Joint United Nations Programme on HIV/AIDS (UNAIDS)/World Health Organization (WHO), showed that the global spread of antiretroviral therapy has been the most important cause of the dramatic decline in AIDS-related deaths from its peak in 2004/2005 to the current moment. New HIV infections have also dropped from 2010 to 2018 in the majority of countries and in all the continents. The degree of decline varied by age group and between men and women, especially among young people. In some countries, young women remain at unacceptably high risk of HIV infection. Other populations at high risk of HIV infections include men who have sex with men, sex workers, and people who inject drugs.

Opportunistic infections (OIs) and neoplasms are important and frequent causes of morbidity and mortality in patients with AIDS, especially in those who did not receive highly active antiretroviral therapy (HAART), those who do not know their serological status in relation to the retrovirus, and finally, those who have a poor adherence to antiretroviral therapy. In some patients, OI represents the first manifestation of immunodeficiency associated with the retrovirus. In our experience, OI involving the central nervous system (CNS) usually occurs as part of two major syndromes: diffuse meningoencephalitis; or cerebral, cerebellum, and brain stem mass lesions. In some cases, the same OI can occur with any one of these major neurological syndromes (e.g., tuberculosis [TB] and CNS reactivation of Chagas disease).

Several studies have shown that early start of HAART may help prevent deterioration of the immunological system and distance patients from the risk of developing serious OIs or neoplasms that may significantly increase morbimortality in this patient population.

Central Nervous System Involvement in HIV/AIDS Patients

Focal brain lesions caused by OIs, neoplasms or cerebrovascular accidents, and meningeal disseminated involvement in the form of meningoencephalitis due to opportunistic pathogens are very frequent neurological complications and are associated with high morbimortality in patients with HIV/AIDS. The right diagnostic and therapeutic approach associated with antiretroviral therapy has contributed to reducing mortality and the incidence of these complications. The use of stereotactic biopsy to obtain an accurate diagnosis in patients not responding to initial empirical treatment for toxoplasmosis is associated with a high diagnostic benefit and with very low morbimortality.

We will analyze brain lesions associated with AIDS of an infectious etiology, then those of a noninfectious etiology, and finally, we will present our experience in the diagnosis and treatment of these lesions.

HIV Brain Lesions of an Infectious Etiology

Toxoplasmosis

Subjects infected with the HIV have a high reactivation incidence of latent infections with Toxoplasma gondii . Incidence varies between 3% and 40%, and it is related to the presence of antibodies against this protozoan in different geographical regions. Approximately 5% of deaths of seropositive HIV patients are associated with toxoplasmosis. ^,

In patients with AIDS, toxoplasmosis usually produces brain abscesses, which have characteristic histopathological changes. Vascular proliferation with endothelial hyperplasia is observed, associated with perivascular inflammatory infiltrate, which may progress to vasculitis with necrosis. Characteristically, the central area is avascular and is surrounded by a necrotic area and by inflammatory cells that may contain free and intracellular tachyzoites; outside this region toxoplasma cysts may be detected. Definitive diagnosis of active toxoplasmosis requires the presence of tachyzoites in tissue biopsies; the presence of multiple cysts near the inflammatory area is highly suggestive of active infection. Staining techniques used to visualize tachyzoites or cysts includes hematoxylin and eosin, PAS, silver methenamine and Giemsa. ^, Lesions may be single or multifocal. They involve both hemispheres and even the infratentorial region, with a predominant location in the basal ganglia, thalamus, as well as the white and grey matter. The pituitary gland and hypothalamus may also be involved. In conclusion, the histopathological picture of toxoplasmosis in AIDS is that of a multifocal necrotizing encephalitis.

Clinical Manifestations

Clinical presentation varies from a subacute and insidious process of a few weeks’ evolution to an acute onset with involvement of the sensorium. The most frequent symptoms at clinical presentation are focal neurological deficits in 70% of cases, headache 55%, mental confusion 50%, and fever 45%. Seizures are the form of presentation in up to 30% of patients, and are more common in toxoplasmosis than in any other opportunistic diseases. ^, Meningeal signs occur in less than 5% of patients, involvement is mainly parenchymal, and meningeal inflammation is rare. ^, Initial neurological signs and symptoms may be focal, nonfocal, or both. Focal abnormalities include hemiplegia, hemiparesis, focal or generalized seizures, personality changes, abnormal movements and cerebellar dysfunction, depending upon the anatomical areas involved. Due to the selective location of the lesions at the level of basal ganglia and brainstem, extrapyramidal symptoms are frequent. Nonfocal manifestations include headache, behavioral changes, fever, lethargy, asthenia, and different degrees of involvement of the sensorium, from confusion through obtundation and stupor to different degrees of coma. Generally, patients who start their clinical presentation without focal abnormalities develop focal neurological signs as the disease progresses. Some ill patients may develop a rapidly fatal disseminated encephalitis without focal lesions on neuroimaging studies. Panhypopituitarism has also been described, associated with inadequate secretion of antidiuretic hormone with hyponatremia. In most patients with AIDS, clinical manifestations of toxoplasmosis tend to be limited to the CNS.

Neuroimaging Findings

Neuroimaging, computerized tomography (CT), and magnetic resonance imaging (MRI) are the imaging tools of choice for patients with suspicion of encephalitis due to T. gondii . Between 60% and 70% present with multiple, bilateral lesions, although they may occasionally be single lesions. They tend to locate in the basal ganglia, frontal and parietal lobes, and in the cerebral white matter, or in the subcortical grey matter. Lesions present in CT as a hypodense central area and peripheral ring enhancement, after the administration of intravenous contrast with perilesional edema. Gadolinium-enhanced MRI is more sensitive than CT and allows detection of a higher number of lesions, or visualization of alterations not observed with CT ( Figs. 130.1 and 130.2 ). Multiple lesions on neuroimaging should be oriented toward infectious etiology, whereas solitary lesions are suggestive of CNS primary causation. ^, Neuroimaging is also used to monitor the response to treatment; reduction in abscess size is confirmed in 90% of patients after 2 to 3 weeks of treatment, and when this occurs, clinical diagnosis is confirmed. ^, ^,

FIGURE 130.1, Toxoplasmosis. T1 magnetic resonance imaging with gadolinium showing several lesions.

FIGURE 130.2, Toxoplasmosis. T1 magnetic resonance imaging showing supra and infratentorial lesions.

Cerebrospinal Fluid Examination

Cerebrospinal fluid (CSF) testing, when possible, is mainly useful to rule out other opportunistic diseases that involve the CNS in patients with AIDS (tuberculous meningoencephalitis, or Cryptococcus neoformans , which require lumbar puncture for diagnosis). CSF testing in toxoplasmic encephalitis reveals hyperproteinorachy (hyperproteinorrachia) in more than half the patients, hypoglycorrhachia and pleocytosis with mononuclear predominance, although a normal study is frequent; thus, it does not rule out the diagnosis. ^,

Polymerase chain reaction (PCR) can be used to detect T. gondii DNA in both CSF and in nervous tissue. Finally, diagnosis is confirmed with stereotactic biopsy and the histological study that shows the characteristics mentioned.

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