Case report

A 50-year-old previously fit and well lady with no vascular risk factors presented to her general practitioner with personality change and emotional lability, against a background of subacutely progressive amnestic syndrome over 3 weeks. She next developed severe anxiety and insomnia and was commenced on citalopram and temazepam. Neurological examination demonstrated universally brisk reflexes with no clonus and downgoing plantar responses. There was marked language difficulty with both expressive and receptive components and ideational and ideomotor apraxia. Formal neuropsychometric testing showed marked impairment in memory, naming, literacy skills and information processing speed (all <5th centile) with relative preservation of executive functioning (phonemic fluency 25th–50th centile). Testing was consistent with marked and pervasive cognitive dysfunction affecting mainly posterior, cortical and subcortical regions.

Full blood count, C-reactive protein, ESR, renal and liver function tests were normal. EEG showed left temporal irregular slowing with occasional low-voltage sharp waves suggestive of epileptiform activity. MRI examination (figure 1A–C) demonstrated extensive confluent areas of T2-weighted hyperintensity diffusely throughout the cerebrum and brainstem. There was no perceptible mass effect, abnormal post-gadolinum contrast enhancement nor restriction of diffusion of the diffusion weighted imaging sequences.

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Figure 1

Brain magnetic resonance imaging (MRI) at presentation (A–C), with coronal (A) and axial (B) T2-weighted sequences demonstrating extensive white matter hyperintensity with no associated mass effect. Note the extension of the hyperintensity along the left corticospinal tract at the level of the cerebral peduncle and pons (white arrow). Axial post-gadolinium contrast T1-weighted imaging (C) did not reveal any abnormal enhancement at this stage. Brain MRI at 6 months after initial presentation (D–F) with coronal FLAIR (D) and axial T2-weighted (E) sequences demonstrating progression and some mass effect of the white matter signal abnormality now involving both corticospinal tracts at the mesencephalic and pontine levels (white arrows). The axial post-gadolinium contrast T1-weighted (F) imaging shows patchy peritrigonal white matter enhancement. Follow-up MRI examination post-therapy (G–I) with coronal FLAIR (G) and axial T2-weighted (H) sequences demonstrating an improvement in the extent and mass effect of the white matter hyperintensity and the resolution of peritrigonal white matter enhancement on the axial post-gadolinium contrast T1-weighted (I) imaging.

The differential diagnoses included infective pathology such as JC virus and HIV, rapidly progressive inflammatory demyelination and genetic metabolic causes. The following were normal or negative: JCV, HIV 1 and 2 and syphilis serology; plasma amino acids, white cell enzymes and very long chain fatty acids levels. Copper studies, coeliac screen, vitamin E levels, autoimmune antibody tests, serum lactate, pyruvate, phytanic and glutaric acid levels were also normal. Cerebrospinal fluid (CSF) examination showed a protein level of 0.74 g/L with a glucose of 3.2 mmol/L (serum 5.5 mmol/L), <1 white blood cell per millilitre and negative oligoclonal bands. CSF PCR for viruses including JC and HIV were also negative. CSF cytology showed a moderately cellular fluid with increased numbers of lymphocytes and macrophages with no atypical cells, consistent with a mild chronic inflammatory/reactive process. Opthalmological screening revealed no evidence of vitreoretinal disease.

Her cognitive symptoms deteriorated over months to the point where she required 24 h nursing care due to significant confusion and anxiety. She became too unwell to engage in formal neuropsychometric tests, but two senior neurologists agreed that she had substantially deteriorated in posterior, cortical and subcortical domains compared with the aforementioned neuropsychometry. A repeat MRI (figure 1D–F) showed more extensive signal changes in the frontal, parietal, occipital and temporal lobes. This also involved the right corticospinal tract, resulting in symmetrical T2-weighted hyperintensity along the paired tracts through the capsular, mesencephalic, pontine and medullary regions. A further focus of T2-weighted hyperintensity was seen in the left cerebellar hemisphere. There was now patchy enhancement in the peritrigonal white matter bilaterally.

Given the rapid clinicoradiological progression and lack of diagnosis, a brain biopsy of an enhancing region in the left parietal lobe was performed. Histological examination showed diffuse and nodular infiltration of cerebrum by large atypical lymphoid cells. The cells showed nuclear pleomorphism and showed clusters around blood vessels and diffuse spread into the surrounding cortex. Further tests confirmed a diffuse large B cell lymphoma.

Following a bone marrow biopsy and PET/CT scan, no evidence of lymphoma outside the central nervous system was found. Treatment commenced, including high-dose methotrexate, cytarabine and rituximab, followed by radiotherapy (40 Gy total). Repeat MRI showed significant improvement in the central nervous system disease (figure 1G–I) and she also improved functionally, being discharged home without a package of care after previously needing 24 h nursing care. Ten months later, functional status had not deteriorated and neuropsychometric testing was equivalent to that done several months prior to commencement of treatment (ie, before significant further cognitive decline), however remaining below premorbid estimates. Importantly, her gait and mobility also improved dramatically as she went from being unable to walk unaided immediately prior to treatment, to walking independently, swimming twice weekly and using a cross-trainer regularly.