Contributed by Widdess-Walsh P, Nair A, Staugaitis SM
Departments of Neurology (PW, AN) and Anatomic Pathology (SMS), Cleveland Clinic Foundation, Cleveland, Ohio 44195.
Published on line in October, 2004
A 49-year-old right-handed man developed progressive cognitive difficulties over a four month period. Recent memory was impaired. He was unable to do the payroll at his company and would get lost in familiar surroundings. There were word-finding and language difficulties. He had associated fatigue, anorexia, daytime somnolence and weight loss of thirty pounds. Gait imbalance and urinary incontinence developed later.
He had a past history of transfusion-associated Hepatitis C, chronic bronchitis, and anxiety. There was no history of chronic alcohol or drug abuse. There was no family history of early dementia.
On examination he was afebrile and normotensive. He was lethargic but would follow basic commands. His level of alertness waxed and waned during the course of his hospital stay. His language was mainly intact with mild dysarthria and dysnomia. Cranial nerve examination was normal. He had increased tone in both lower extremities. The left arm tone was increased with 4/5 MRC grade weakness. Sensory examination was normal although he had left sided neglect. Bilateral Babinski signs were present, and he had a prominent grasp reflex. He was unable to walk unaided.
Laboratory testing showed normal acute phase reactants, thyroid function tests, and an autoimmune screen. Tests for Lyme, Borrelia, Syphilis, cryptococcus and HIV were negative. The CSF showed 4 x 106/L WBC, no red cells, protein of 34 g/dL, and normal cytology (two lumbar punctures). Paraneoplastic antibodies were negative. CMV and EBV PCR were negative. An EEG showed generalized intermittent slowing suggestive of a diffuse encephalopathy and decreased background in the right hemisphere, suggestive of a structural lesion.
MRI showed areas of high signal on FLAIR imaging (Figure 1) in the bilateral frontal and parietal white matter consistent with an infiltrative process. Gadolinium enhanced images showed patchy enhancement indicating blood brain barrier disruption (Figure 2). A four-vessel cerebral angiogram showed no evidence of vasospasm to suggest a CNS vasculitis. A right carotid injection is shown in Figure 3. A fluoro-deoxyglucose positron emission tomography (FDG-PET) scan to assess the metabolic nature of the lesions showed multi-focal areas of increased uptake, suggestive of actively metabolic structural lesions (Figure 4). The signal identified by the arrow in PET image 49 correlates with the area of enhancement on MRI (Figure 2, arrow). There was diffusely decreased uptake in both hemispheres including the subcortical nuclei, suggestive of widespread cortical dysfunction. There were no focal metabolic defects to suggest infarction or severe ischemia. There was preserved activity in the posterior parietal, parieto-temporal cortices and frontal lobes; these findings did not support an Alzheimer's type or frontal dementia.
A brain biopsy was performed. The specimen showed diffuse infiltrates of large malignant cells with large nuclei and prominent nucleoli (Figure 5). These cells were immunoreactive with antibodies to CD20 (Figure 6).
DIAGNOSIS AND DISCUSSION