Neurological manifestations, laboratory and neuroimaging features in HIV-infected patients

Discussion

With the advent of highly active antiretroviral therapy era since 1996, it has led to a dramatic improvement in the prognosis and survival of individuals with HIV infection.2 However, the spectrum of neurologic manifestations of HIV infection is broad and thus the diagnosis and treatment are still challenging. HIV may affect the nervous system directly, producing a variety of neurological syndromes, or indirectly, resulting in susceptibility to opportunistic infections attributable to immunodeficiency.

Our study found that the clinical scenario of HIV infection could be presented with encephalopathy/encephalitis characterized by manifestations such as mental and psychomotor slowing, memory deficit, indexterity of limbs, gait disturbance, speech disorder or seizure, and concomitant preferential subcortical involvement in brain MRI. Meanwhile, confounding factors that may play roles in cognition such as old age or cerebrovascular disease did not exist in those patients. If the neuroimaging weren’t taken into consideration, this group of syndromes would be tentatively summarized by the term “HAND”.3-5 Impairment of fine manual dexterity and gait disturbance could also develop in HIV-infected patients,6 consistent with our study.

The asymmetric brain lesions were in contrast to the classical neuroimaging features of HIV-D which are supposed to be diffuse atrophy and symmetrical lesions in white matter.6 For case 1, the neuroimaging manifestations characterized by multiple asymmetric bilateral lesions in subcortical white matter and lack of global brain atrophy (Figure 1 A, B), therefore, raised the consideration of the diagnosis of PML. However, the confirmation of PML diagnosis requires CSF polymerase chain reaction for JCV DNA.7 Brain damage of HIV encephalopathy occurs mainly in the subcortical gray matter, especially basal ganglia, which may be pivotal in subcortical dementia due to HIV infection8. It remains unresolved as to the definite etiological diagnosis of encephalopathy/encephalitis owing to lack of the specific etiological agent confirmation tests, such as genetic test for virus.

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Figure 1

Magnetic Resonance axial T2-weighted A) and FLAIR B) (case 1) image displays diffuse subcortical lesions in right temporal, frontal, parietal, occipital lobes, and left parietal lobes. C) (case 9) image displays multiple subcortical lesions in bilateral hemispheres. D) (case 12) image displays multiple lesions in bilateral basal ganglia, centrum ovale and subcortical regions.

As regards the infarction mechanisms in HIV-infected patients, it is variable, with a relatively high incidence of vasculitis and hypercoagulability (including acquired protein S deficiency and anticardiolipin antibodies).9 Furthermore, HIV-infected individuals have an increased risk of venous thrombo-embolismand stroke.10 In our study, no salient clues to infarction-associated factors were discovered, we therefore speculated that vasculitis secondary to HIV infection might be the important cause of infarction. Previous autopsy study indicated that basal ganglia and deep white matter were preferential regions of productive HIV infection after HIV accessing the brain.11,12 Upregulation of chemokines and cytokines was also prominent in the basal ganglia.13 This seems to explain the regional susceptibility in HIV-infected patients. However, whether the cerebral infarctions should be considered a primary event related to HIV infection or not is unclear.

Cryptococcal meningoencephalitis was diagnosed in one patient (case 8), with general encephalitis symptoms such as fever, headache and loss of consciousness, further supported by prominent features such as positive ink stain of CSF and raised intracranial pressure. Cryptococcal meningoencephalitis is one of a variety of common opportunistic infections in HIV-infected patient.14 It was reported that brain-imaging findings may be nodules, masses, pseudocysts, or dilated Virchow-Robin (VR) spaces, and non-specific or normal for cryptococcal meningoencephalitis.15 In agreement with the report, there was no obvious abnormality in neuroimaging of the patient in our study. It reminded clinicians that normal brain imaging did not rule out cryptococcal meningoencephalitis.

One patient (case 6) had typical symptoms of intracranial hypertension, and died during the hospitalization. The MRI showed multiple diffused bilateral lesions with ring-like gadolinium enhancement, perilesional edema and mass effect. It is widely thought that the ring-enhancing lesions were common in cerebral toxoplasmosis.16

The patient diagnosed with peripheral neuropathy (PN) favoring chronic Guillaine-Barre syndrome (GBS) (case 2) had concomitant Hashimoto’s thyroiditis (HT), consistent with the report that concurrent GBS, myasthenia gravis, or other immune disorders, developed in a patient with HT.17,18

There are few reports where an multiple sclerosis (MS) -like disorder occurred in the presence of HIV infection.19,20 However, it was of considerable interest that the neurological conditions of MS in HIV-infected patients were associated with the HIV viral load and CD4+ cell count.21 It thus raised the speculation that HIV infection and the subsequent HIV-mediated immunomodulation might be a possible basis of the pathogenesis of the CNS demyelinating disorders.

Serum biochemical analysis appeared to provide limited evidence for HIV infection. Increased level of ESR was found in HIV-infected patients in our study, consistent with the previous study indicating the ESR in patients with HIV infection was significantly higher than those of the controls.22 Although elevated ESR can be found in various infectious or immune disorders, and the use of ESR to evaluate the condition or predict the development of AIDS is still under investigation, it might be somewhat helpful to measure ESR for HIV infection.23

The limitations of our study included: first, the diagnosis were basically clinical and even speculative in the retrospective study, because we failed to conduct on more detailed etiological investigations or follow-up study; second, the number of cases was too small to make any statistical analysis; third, it would provide more significant implications if the information of viral load and CD4+ cell count were acquired to reflect the severity of HIV infection. Large-scale prospective thorough study, therefore, would be needed.

In conclusion, the neurological presentations in HIV-infected patients were remarkably broad, and neuroimaging changes involved brain or peripheral nerves due to the variable profiles. Patients who presented with neurocognitive impairment mostly had asymmetric brain lesions. There will be a greater need for further prospective comprehensive study.