HIV Presenting as Young-Onset Dementia

Abstract

With the advent of retroviral therapies, the incidence of severe dementia associated with HIV has been reduced, although minor neurocognitive impairment is being increasingly recognized in the course of illness. We report a case of a young woman presenting with HIV-associated dementia and raise awareness of its presentation in young age and as the first presenting symptom.

Introduction

HIV leads to varied neurological complications such as HIV-associated myelopathy or neuropathy, HIV-associated cognitive and motor disorders, opportunistic infections, and neoplasms. HIV-associated dementia (HAD; also termed as subacute encephalitis, HIV dementia, AIDS dementia complex [ADC], or HIV encephalopathy) is a subcortical dementia that is characterized by a combination of cognitive/behavioral and motor dysfunction. Currently, the term HIV-associated neurocognitive disorder (HAND) encompasses entire spectrum of neurological disease, beginning with asymptomatic neurocognitive impairment (ANI), to minor neurocognitive disorder (MND) and HAD. ¹ The diagnosis is based on clinical criteria and the absence of other diseases that may explain the condition and requires a thorough clinical examination along with radiological imaging of the brain and cerebrospinal fluid (CSF) analyses.

HIV-1 is the most common preventable cause of neurological decline in persons younger than 50 years of age. Individuals with HIV experience some form of neurocognitive decline affecting activities of daily living in 30% to 50% of the cases. ^1,2 Prior to availability of antiretroviral therapy (ART), dementia was observed in approximately 16% of the patients. ¹ With the availability of highly active antiretroviral therapy (HAART) and its widespread use in the developed world, the epidemiology of HAND has undergone a remarkable shift with reduced incidence of HIV dementia (less than 5%) but persistent problem of milder but significant neurocognitive impairment. ^1,2 In developing countries, still significant proportions of individual develop florid dementia called HAD. ^1,2 Although dementia is seen in HIV-infected individuals during the course of illness, no case is reported to present only with dementia in our literature search. We present a case of a young woman who initially had fever, followed by rapidly progressive cognitive impairment and prominent motor dysfunction. The patient was subsequently found to be HIV-1-infected.

Case Report

A 24-year-old unmarried woman presented with 9 months’ history of abnormal behavior and depressed mood, 6 months’ history of tremulousness of both the hands, and history of urinary and bowel incontinence for 3 months. She stopped taking care of self and started showing disinterest and apathy toward day-to-day activities. She was noted to have skin rashes all over the body. There was no elicitable history of being sexually active or assault from attendant. Eleven months prior to presentation, the patient had fever for a duration of 3 months. No definite cause of fever was established during her investigations at another center at that time. On examination, she appeared emaciated, had oral candidiasis, and hyperpigmented skin lesions. The patient was observed to be conscious, with impaired sustained attention and recent memory. The patient scored 21 of 30 on the Mini-Mental Status Examination. She had expressionless face with bilateral upper limb action tremors, symmetrical rigidity, and exaggerated deep tendon reflexes. Plantar reflexes were bilaterally flexor. She was investigated and noted to have normocytic, normochromic anemia (Hemoglobin = 9.8/dL), hypocalcemia (serum calcium = 7.2mg/dL), and transaminemia (serum glutamic oxaloacetic transaminase = 228U/L; serum glutamic pyruvate transaminase = 199U/L). Further investigation revealed elevated thyroid-stimulating hormone and antithyroid peroxidase antibodies. Serum copper, serum ceruloplasmin, and antinuclear antibody were normal. Chest X-ray and ultrasound of the whole abdomen were normal. Magnetic resonance imaging of the brain revealed diffuse cortical atrophy (Figures 1 and 2). The CSF analysis showed clear acellular fluid with high normal protein level and normal glucose. The fluid was negative for acid-fast bacilli by Ziehl-Neelsen stain and for Cryptococcus by India ink stain. Finally, in view of the relatively rapid onset of cognitive impairment with prominent motor symptoms, the patient was checked for HIV and was found to be positive by AIDS Comb, Acon, and Retroquick tests. Subsequently, CD4 count was performed and noted to be <30 cells/mm³. She was diagnosed with HAD. However, she died suddenly before we could initiate ART.

Figure 1.

Magnetic resonance imaging scan showing diffuse cerebral atrophy.

Figure 2.

Magnetic resonance imaging scan showing diffuse cerebral atrophy.

Discussion

Early in the AIDS epidemic, it was noted that neurocognitive impairment was present in a subset of patients with advanced disease suggesting that the underlying pathogen likely affected the central nervous system. It was not known at that time that the impairment could be due to HIV itself. The neurocognitive impairment attributable to HIV was controversial until 1987, when the first comprehensive study of HAND was published. ¹ In 1991, AIDS Task Force of the American Academy of Neurology proposed 2 levels of neurocognitive disturbance in patients with HIV. ¹ Minor cognitive motor disorder included the HIV-associated neurocognitive impairment that did not meet criteria for HAD but was marked by impairment in at least 2 neurocognitive or behavioral areas producing a decline in activities of daily living. With the advent of HAART, it has been felt that the classification of neurocognitive impairment in HIV-infected patients needs further refinement and standardization. The HAND is a potentially multifactorial condition defined by a combination of the patient’s reported symptoms and measured abnormalities on neuropsychological test performance. The HAND is subclassified into 3 categories, asymptomatic neurocognitive impairment, MND, and HAD. Unlike other dementias, the diagnosis of HAND does not formally include additional biomarkers (either from the CSF or through neuroimaging).

Without treatment, HAD is typically rapidly progressive with a mean survival of about 6 months, less than half the average survival of nondemented patients with AIDS. ³ Those with CD4 counts of <100 progress more rapidly. Survival of patients has improved since the introduction of HAART with promising results with zidovudine (ZDV), abacavir (ABC), stavudine (d4T), and lopinavir/ritonavir (LPV/r). ¹

The HAND is frequently detected in patients receiving antiretroviral treatment. Even HAD, which overlaps in clinical presentation considerably with severe forms of ADC as described in the past, includes a spectrum of disease from inactive to active and may reflect neuropathologic events within the central nervous system distinct from those associated with dementia that occurs solely in the absence of ART.

Combination (potent) ART has reduced the prevalence of severe HAND but not the prevalence of mild to moderate HAND that ranges from 39% to 52% in varied settings. ^2,4,5

In developed countries, effective early institution of HAART has resulted in decreased frequency of HAD and increasing recognition of asymptomatic and minor cognitive disorders. In developing countries like India, physicians are likely to see florid cases of HAD due to delay in diagnosis and recognition of HIV infection and delayed institution of HAART. Further, dementia may not be perceived to be due to HIV in the absence of other features or risk factors for HIV infection.

In our patient, the cognitive and behavioral impairment was seen along with prominent extra pyramidal and pyramidal features as presenting symptoms. No history about sexual assault or activity could be obtained. Moreover, there was no definite history of other risk factors for HIV. The patient had fever for 3 months, about 11 months prior to presentation. But, apparently she was not subjected to HIV testing at that time. This case highlights the importance of HIV testing in every case of pyrexia of unknown origin and the need to suspect HIV as one of the causes for young onset rapidly progressive dementia. Early detection of HIV infection and institution of HAART could have possibly reduced the chance of developing florid dementia and premature death of the patient. This case highlights the importance of early recognition of HIV and appropriate institution of HAART.