CNS Case

Presentation

Peter, a 66-year-old male, complained of a persistent headache during a routine follow-up appointment to monitor the immunosuppressive medication he takes for a heart and lung transplant he received 3 years ago. The headache initiated in the occipital region approximately 8 weeks ago, then later shifted to the frontal area. He initially downplayed the severity of the headache, but further questioning showed several worrying signs.

Clinical examination revealed photophobia, left-sided weakness, and occasional tingling sensations in his left upper limb. Neurological assessment indicated mild cognitive impairment and weakness in the left upper limb.

He has also had type 1 diabetes since childhood, but it is generally well-controlled using his insulin pump

“I’ve been having this dull headache for a few weeks now, but it is really starting to bother me and so I want to get it checked out.”

Referred from	Transplant clinic
Diagnoses	Diabetes mellitus type 1 (insulin pump); heart-lung transplantation (Cyclosporine 200 mg twice daily)
Demographics	66M Immunocompromised
Vital signs	Blood pressure (BP): 140/90 mmHg Resting heart rate (RHR): 82 bpm Body mass index (BMI): 26.7 (5’10″/80 kg) HbA1C: 7.2%

Which tests would you order?

Blood Culture

[Correct]: Assesses potential bacterial or fungal infections causing the symptoms and guide appropriate treatment.

Complete Blood Count

[Correct]: Evaluates overall blood cell counts, including white blood cells, indicating infection or inflammation.

Brain Imaging (MRI/CT)

[Correct]: Visualizes the brain for lesions, abscesses, or abnormal tissue.

EEG

[Incorrect]: While relevant for brain activity, infection-focused tests like blood culture, fungal culture, and PCR for pathogenic DNA are more suitable here.

Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP)

[Correct]: Markers of inflammation, helping assess infection severity.

Fungal Culture

Tests specifically for fungal pathogens in the bloodstream.

Tissue Biopsy

[Possibly]: A biopsy directly confirms infection but is invasive and not routine due to risks and expertise.

Lumbar Puncture (LP) and Cerebrospinal Fluid (CSF) Analysis

[Correct]: Examines cerebrospinal fluid for infection signs, white blood cells, protein levels, and pathogens.

Polymerase Chain Reaction (PCR) for Fungal DNA

Detects fungal DNA/RNA for rapid and specific pathogen identification.

Test results

Test	Result (range)
Blood cultures	Negative for Aspergillus fumigatus.
Complete blood count	Elevated white blood cell count, indicative of infection.
Imaging	Initial CT scan revealed a single well-defined 12mm lesion with distinct borders within the parenchyma. Midline shift, infarction and ventricular effacement were not observed MRI showed mixed signal intensity on T1 and T2-weighted images. Post-contrast images reveal peripheral rim enhancement, with surrounding hyperintense areas indicating mild perilesional oedema.
ESR & CRP	Elevated, consistent with inflammation.
CSF analysis	Elevated white blood cell count & increased protein levels Aspergillus PCR positive Culture positive for Aspergillus fumigatus

What is his diagnosis?

Cerebral Aspergillus Abscess

His clinical symptoms are well-explained by a cerebral abscess, which he is known to be at risk of due to immunosuppresion

Positive fungal cultures and Aspergillus PCR are strong evidence of a fungal cause

Bacterial brain abscess

While his symptoms can be caused by a bacterial abscess, the positive fungal cultures and positive Aspergillus PCR are strong evidence of a fungal cause in this case

Furthermore, the absence of typical risk factors for bacterial brain abscess such as sinusitis, dental infections or recent head trauma makes this diagnosis less likely.

Ischaemic stroke

Headache, left-sided weakness and tingling sensations are common in ischaemic stroke. However, his imaging results found a clear lesion and not the typical signs of stroke (e.g. restricted diffusion on MRI, or infarcted area on CT ).

Infection should always be suspected for patients receiving immunosuppressive medication

Treatment

Peter was prescribed intravenous voriconazole, starting with a loading dose of 6 mg/kg every 12 hours for the initial 24 hours, followed by a maintenance dose of 4 mg/kg every 12 hours. TDM was used to monitor his serum drug levels and his blood glucose was monitored closely. An ECG was performed as this medication can occasionally cause long QT syndrome

Oedema and inflammation were managed using corticosteroids, particularly dexamethasone. Repeat imaging and CSF cultures were used to monitor response to treatment.

Surgical intervention to drain and biopsy the lesion were discussed as an option in case the abscess failed to respond to medical management

Outcome

After 10 days of IV voriconazole, his CSF tested negative for Aspergillus and his headache had improved somewhat. CT scan showed the oedema had lessened, but the lesion had not yet begun to improve substantially

The antimicrobial pharmacist recommended it was safe to step down to oral voriconazole, which allowed him to be discharged home. He will stay on antifungal treatment for at least 6 months and receive regular follow-ups and repeat CT scans