Rapid Cognitive Decline in a Patient With Chronic Lymphocytic Leukaemia

A Case Report

James Forryan; Jun Yong

Disclosures

J Med Case Reports. 2020;14(39) 

In This Article

Case Presentation

A Caucasian male in his late 60s with a background of TP53-negative chronic lymphocytic leukaemia (CLL) presented through the Emergency Department with reduced mobility and confusion of 2 weeks' duration. The diagnosis of CLL had been made 4 years prior and was originally staged as Binet A (less than three areas of lymphadenopathy and with no anaemia or thrombocytopaenia); unfortunately, the profound progression of symptoms and lymphadenopathy in the preceding year had necessitated a progression from surveillance to active management. The patient had therefore been enrolled in the RIALTO trial and completed six cycles of ofatumumab and chlorambucil 2 months prior to this presentation. Notably, a subtler deterioration in memory had occurred in the 2 months prior to admission, but before this, the patient was fully independent with normal cognition.

Other comorbidities included fatty liver changes, gout and recurrent respiratory tract infections associated with hypogammaglobulinaemia. A comprehensive medical history (including drug history) failed to explain his symptoms. No relevant family or travel history was present. On initial assessment in the Emergency Department, physical examination was unremarkable except for a Glasgow Coma Scale (GCS) score of 14/15 due to confusion. Neurological examination in the Emergency Department was documented as normal.

Routine bloodwork on admission (including full blood count, bone, renal and liver profile, thyroid function testing and vitamin assessments) was unrevealing. The white cell count was 6.6, with neutrophils of 4.8 and lymphocytes of 1.2. A chest X-ray and computed tomography (CT) brain demonstrated no acute lung or intracranial pathology, respectively. Microbiological sampling of the stool, urine and blood demonstrated no organisms on smear or culture. A CT neck/thorax/abdomen/pelvis showed interval improvement in the size of enlarged subcarinal, portocaval, right iliac and left iliac lymph nodes (compared to a previous CT of 8 months prior) and stable splenomegaly.

Early in the admission, concerns were raised by various members of the team about progressive cognitive impairment, loss of independence, inability to follow simple commands and a lack of insight. A further neurological examination was undertaken on admission to a medical ward which revealed diminished reflexes and an extensor right plantar response. A brain magnetic resonance imaging (MRI) (Figure 1) then demonstrated white matter hyperintensities in the frontal lobes, with restricted diffusion in a flame front configuration surrounding the lesions. No abnormal enhancement was seen.

Figure 1.

(a) Axial T1-weighted magnetic resonance imaging (MRI) showing asymmetric hypointense areas in the bilateral frontal white matter (arrows). (b, c) They appear hyperintense on the corresponding T2-weighted and FLAIR sequences. (d) The lesions do not enhance following intravenous contrast administration. (e, f) A thin rim of diffusion restriction can be seen along the advancing edge of the lesion on the DWI images and the corresponding ADC maps (arrowheads)

The MRI appearances, in conjunction with the clinical syndrome presenting itself, were felt to be highly suggestive of progressive multifocal leukoencephalopathy (PML). Other differentials, such as secondary central nervous system (CNS) lymphoma and CNS CLL infiltration, were considered less likely due to an absence of the typical avid enhancement usually seen on MR imaging. To help confirm a diagnosis, CSF analysis was undertaken. No organisms were grown from the CSF, and the white cell count was 44 per c.mm (100% lymphocytes). CSF protein was raised at 0.68. The CSF virology and opportunistic infection screen (cryptococcal, toxoplasma and Mycobacterium tuberculosis) were negative apart from detection of John Cunningham virus (JCV) via polymerase chain reaction (PCR), with a quantitative value of 41,850 gEg/ml; the symptomatology, radiological findings and CSF analysis were considered confirmatory of PML. The CSF immunophenotyping and morphology demonstrated no features of CLL or lymphoma. Ultimately, a brain biopsy was not performed because this would not have influenced the management, and the invasive nature of the procedure would have carried considerable risk given the patient's performance status. We involved our palliative care colleagues in the care of this gentleman and were able to facilitate discharge to a hospice for ongoing symptom control and care. The patient sadly passed away roughly 3 months after the diagnosis of PML.

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