Contributed by Jan Rémi, Thomas Pfefferkorn, Fatima B. König, Hans Lassmann, Wolfgang Brück, Markus Holtmannspötter, Andreas Straube, Hans A. Kretzschmar and Ulrich Schüller
From the Departments of Neurology (J.R., T.P., A.S.), Neuroradiology (M.H.), Neuropathology (H.A.K., U.S.) of the University of Munich, Germany, the Department of Neuropathology of the University Medical Center of Göttingen, Germany (F.B.K., W.B.), and the Center for Brain Research of the University of Vienna, Austria (H.L.)
CLINICAL HISTORY AND NEUROIMAGING
A 76 year old woman was admitted to a spinal trauma hospital after a collapse at home with paraplegia and total loss of deep tendon reflexes of unknown duration. Upon admission she was responsive but not well orientated. A spinal MRI showed T2 signal enhancement from Th4 to L2, without revealing evidence of the etiology. Over the course of the next 3 days her mental status decreased to where she could only be woken up with strong pain stimuli. Leukocytosis (30.3 G/l) and fever (39°C) were noted. In a cerebral computed tomography, several hypodense white matter lesions were visible. The cerebrospinal fluid (CSF) contained 61 cells/µl with 3.33g/l protein and 1.8mmol/l glucose (serum: 6.0 mmol/l) and treatment with broad spectrum antibiotics and glucocorticosteroids was started.
On hospital day 5 she was transferred to our neurological intensive care unit because of deteriorating mental status and the need for mechanical ventilation. On day 12, an axial FLAIR-weighted MRI showed large confluent white matter lesions in the brain (Figure 1). Similar abnormalities were found in the spinal cord. The lesions showed no signal enhancement on diffusion weighted imaging, but had patchy gadolinium contrast enhancement. CSF cell, protein and glucose levels remained stable over several lumbar punctures, and CSF specific antibody production was shown with CSF specific oligoclonal bands. Microbiological CSF analyses were negative for bacterial or viral pathogens, including JC-virus and enteroviruses. Anti-aquaporin 4 antibodies were not detectable. The peripheral leukocytosis of her blast crisis peaked at 102 G/l. No BCR-ABL rearrangement was detectable. The patient's condition continued to deteriorate despite antimicrobial and steroid treatment. The patient died on hospital day 16.
Over the three and a half years prior to admission, the patient had unintentionally lost 10-15 kg of body weight, and there had been an extensive work-up for a neoplasm which yielded no specific pathological results. A bone-marrow biopsy three years ago had not retrieved enough bone marrow cells at that time to be conclusive, the blood leukocyte levels in the previous three years were around, the high normal limit (but never above). Her other past medical history was noncontributory.
The post mortem analysis secured the diagnosis of an acute myeloid leukemia (AML, subtype M2) in bone marrow, spleen (weight: 380g) and liver. No other neoplasm was found. The analysis of brain tissue revealed large, partly confluent lesions in the white matter of both cerebral hemispheres as well as the spinal cord. A representative gross image is shown in Figure 2 demonstrating a well-demarcated lesion in the right occipital lobe. Distinct lesional areas within the cerebral white matter are visible in a Luxol-Fast-Blue stain (Figure 3). Axonal destruction varied, but was severe in some areas. GFAP+ reactive astrocytes and macrophages with LFB-positive material (Figure 3, insert) were detectable throughout the lesions. C9neo+ complement deposits were also present at sites of active demyelination (Figure 4, brown signal). This is a pattern of pathology that is typically seen in the antibody- and complement-mediated pattern II of multiple sclerosis lesions according to the classification scheme of Lucchinetti et al.
. Blood vessels as well as perivascular spaces within the lesions were packed with myeloblasts (Figure 5). The spread of myeloblasts was most severe within the lesions, but they could also be found throughout the whole brain parenchyma outside the lesions.