Atypical presentation and diagnosis of AIDS-related CMV encephalitis

Background

This case of a patient with AIDS-related cytomegalovirus (CMV) encephalitis presents an example of retrograde diagnosis of an opportunistic central nervous system infection in a patient with an initial presumed diagnosis of toxic encephalopathy. From this case, we highlight three main teaching points. First, AIDS-related CMV encephalitis can present with brainstem and cerebellar lesions on imaging, manifesting as profound ataxia. Second, vigilance is needed in corroborating symptoms with radiographical findings. Our patient’s persistent ataxic symptoms while he was no longer abusing amphetamines or mushrooms, as well as abnormal signal in the cerebellar white matter on MRI, were inconsistent with a diagnosis of toxic encephalopathy and ultimately prompted a lumbar puncture to secure the diagnosis. Third, thorough history gathering to assess risk of immunocompromised status can broaden an initial differential, avoid anchoring bias and facilitate prompt diagnosis when evaluating a patient with neurological symptoms. In our case, neither CMV nor HIV was considered initially; it was only through persistence of ataxia and the MRI that we were pointed towards the diagnosis.

Case presentation

A right-handed man in his 40s with a medical history significant of post-traumatic stress disorder, presented to the emergency department (ED) with altered mental status, ataxia, blurred vision, headache and dizziness. He was brought to the ED because of reported erratic behaviour.

The patient reported recent use of amphetamines and mushrooms. He frequently used such drugs but denied injection drug use.

The patient also reported moderate bitemporal headache and weight loss. He denied chest pain, shortness of breath, cough, fever, seizures, upper respiratory tract symptoms, seizures, changes in bowel or urinary habits, night sweats or sick contacts.

On examination, he was tachycardic (heart rate 110–130 beats per minute) and hypertensive (blood pressure was 168/96 mm Hg in the ambulance, but normal throughout ED course). Patient was visibly anxious though not in distress.

Neurological examination revealed a non-cachectic, alert man, oriented to self and place, but not time, with non-bizarre delusions. Attention was intact, however, noted to have significant memory impairment, with two attempts needed for immediate recall and 1/5 on delayed recall: 3/5 with prompting. Speech was fluent, no dysarthria or aphasia. He followed multistep commands across midline. Gait was wide based and unsteady; the rest of neurological examination, including strength, sensation, cranial nerve examination and coordination, was intact.

Investigations

Initial haematology results were significant for mild leucopenia (White Blood Cells 3.2 K/µL) and mild normocytic normochromic anaemia (haemoglobin 106 g/L, MCV 91.8 fL and MCH 28.8 pg). A comprehensive metabolic and lipid panel were both within normal limits. Urine toxicology was positive for methamphetamines.

Twenty-four hours after presentation, the patient’s ataxia and dizziness failed to improve, and a CT of the head without contrast was performed revealing possible periventricular hypodensities. To further clarify these findings, an MRI of the brain without contrast was performed, which showed extensive confluent T2 hyperdense signal throughout the cerebral white matter, brainstem and cerebellar white matter (figures 1 and 2). These findings prompted the possibility of immunocompromised-related leucomalacia.

Figure 1

T2 FLAIR MRI brain showing hyperintense signal to the cerebellar white matter.

Figure 2

T2 FLAIR MRI of the brain showing hyperintense signal extending into the brainstem.

Based on these brain imaging findings and the persistent ataxia and dizziness, additional history was obtained to assess risks for immunocompromised status. The patient noted he was sexually active with multiple male partners and did not use protection. A subsequent HIV test was positive, with a viral load 96 800 cp/mL, CD4 22 cells/μL, with 2% CD4. Syphilis serology and Rapid Plasma Reagin (RPR) were also reactive, with quantitative RPR of 1:16, negative serum QuantiFERON Gold+ and cryptococcal antigen. His qualitative serum CMV PCR was positive, CSF findings: no white blood cells, no red blood cells, normal glucose, and elevated protein. CSF meningoencephalitis panel was positive for CMV. Other CSF studies were negative for acid-fast stain and culture, cryptococcal antigen, VDRL (Venereal disease research laboratory test), toxoplasmosis (both IgM and IgG), JC virus, and EBV.

Differential diagnosis

Our patient presented with altered mental status, ataxia, blurred vision and headache in the setting of recent substance use. The most likely diagnosis was toxic encephalopathy associated with amphetamine use; this was supported by tachycardia, nervousness, mood disturbances, disorganised thinking, loss of appetite and weight loss.1 Also of consideration was posterior reversible encephalopathy syndrome in the setting of a blood pressure spike during amphetamine use. Other differentials include nutritional deficiencies and demyelinating and ischaemic brain diseases, although he did neither have focal neurological deficits nor risk factors for vascular disease.

Treatment

After his lumbar puncture results revealed CMV, the patient was transferred to the neurology service and followed closely by the infectious disease team. Ganciclovir 5 mg/kg/dose intravenously was administered every 12 hours for 3 weeks. Ophthalmology services ruled out CMV retinitis since a strong association between CMV retinitis and encephalitis is apparent. In an autopsy series of 47 patients with AIDS, 75% of those with CMV retinitis involving the peripapillary area also had encephalitis.2

The patient was also treated for latent syphilis with penicillin G 2.4 MU intramuscular weekly for three doses. Additionally, he was placed on azithromycin 1200 mg orally every week for Mycobacterium avium complex (MAC) prophylaxis and bactrim double strength one tablet three times weekly for Pneumocystis jiroveci pneumonia (PJP) prophylaxis.

While still in-patient, and after completing a course of intravenously ganciclovir, he was started on bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy), one tablet daily, and switched to oral valganciclovir 900 mg daily maintenance therapy, which he is still taking.

Outcome and Follow-up

Two weeks into treatment with intravenous ganciclovir, the patient’s headaches, dizziness, blurry vision and memory recovered completely, ataxia also improved, but he remained with a wide-based gait throughout the hospital stay.

A week after discharge, the patient followed up as an outpatient with the infectious diseases’ clinic at which time his gait had returned to normal, and he was recommended to undergo physiotherapy at home.

He has since returned to work, without any neurological deficits, reports adherence to all his medications, and continues to follow-up closely with his newly established primary care physician.