A 41-Year-Old Man With Forgetfulness
A 41-year-old man presents with a progressive neurologic illness during the past 6 months, including forgetfulness, disorganization at work, personality changes, irritability, amnesia, and delusions. Neurologic examination shows mild dysmetria of all 4 limbs, a wide-based ataxic gait, extensor plantar responses, and the presence of primitive reflexes. Formal mental status testing reveals disorientation; perseverative speech; tangential rambling sentences; and impairment of word generation, three-dimensional constructions, and clock drawing.

Primitive reflexes include (more than 1 answer is correct):

1. 
   Crossed adductor
   
2. 
   Hoffman's sign
   
3. 
   Abdominal reflexes
   
4. 
   Oppenheim's sign
   
5. 
   Snout reflex
   
6. 
   Myotonia
   
7. 
   Rooting response
   
8. 
   Tromner's sign
   
9. 
   Corneal reflex
   
10. 
    Decorticate posturing
    

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<p>Snout reflex</p><p>Rooting response</p>


Which of the following best describes the clinical diagnosis?

1. 
   Factitious illness
   
2. 
   Acute stroke
   
3. 
   Psychiatric
   
4. 
   Status epilepticus
   
5. 
   Dementia
   

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<p>Dementia</p>


Which is of the following diseases can cause this clinical picture?

1. 
   Degenerative disease
   
2. 
   Infection/inflammation
   
3. 
   Metabolic disease
   
4. 
   Neoplasia
   
5. 
   All of the above
   

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<p>All of the above</p>


Results of noncontrast magnetic resonance imaging (MRI) are shown in Figure 1. The lesions are non-enhancing (not shown).


(Enlarge Image)

Noncontrast axial T2-weighted (far left, middle left, middle right) and noncontrast T1-weighted (far right) MRI scans of the brain performed 6 months after the onset of mental status changes. Representative slices are shown. Lesions are non-enhancing (not shown). Reprinted with permission from Bakshi et al. Dementia and Geriatric Cognitive Disorders. 1999;10:152-157.

Which of the following is TRUE of the MRI findings?

1. 
   Lesions show hypointensity on T1-weighted images
   
2. 
   Lesions are calcified
   
3. 
   Lesions are hemorrhagic
   
4. 
   B and C
   
5. 
   None of the above
   

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<p>None of the above</p>


Which of the following is TRUE of the lesions?

1. 
   Marked T2 shortening
   
2. 
   Marked T2 prolongation
   
3. 
   Marked T1 shortening
   
4. 
   Marked T1 prolongation
   
5. 
   A and C
   

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<p>Marked T2 prolongation</p>


Which of the following is true of the lesions?

1. 
   Predominantly biparietal and bioccipital
   
2. 
   Marked involvement of the pons
   
3. 
   Marked involvement of the basal ganglia
   
4. 
   Largely extra-axial
   
5. 
   None of the above
   

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<p>Marked involvement of the pons</p>


Widespread bilateral hyperintense lesions on T2-weighted images involving the periventricular white matter, subcortical white matter, gray-white junction, portion of the cerebral cortex, and brain stem, with bifrontal, bitemporal, and bilateral pontine predominance. The lesions extend into the corpus callosum, but show relative sparing of the basal ganglia and thalamus. The lesions in the left operculofrontal lobe show mild T1 hypointensity, but otherwise the lesions are poorly appreciated on T1-weighted images. Following contrast administration, the lesions are nonenhancing (not shown).

The lack of marked hypointensity of the lesion on T1-weighted images makes which of the following unlikely:

1. 
   Progressive multifocal leukoencephalopathy
   
2. 
   Diffusely infiltrating neoplasm
   
3. 
   Neurodegenerative disease
   
4. 
   Prion disease
   
5. 
   HIV encephalitis
   
6. 
   Vasculitis
   

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<p>Progressive multifocal leukoencephalopathy</p>


High-dose intravenous methylprednisolone was started empirically (1g IV/day x 5 days) but had no effect. Unremarkable serum studies included: angiotensin converting enzyme, HIV-1, HIV-2, C3, C4, antinuclear antibodies, antiphospholipid antibodies, anti-SSA, anti-SSB, Lyme titers, lactate, and Epstein-Barr virus titers. Two additional lumbar punctures showed no change in the CSF findings including negative cytology and negative flow cytometry. Unremarkable CSF studies included VDRL, coccidiomycosis antibodies, cryptococcus antigen, viral culture, tuberculosis culture and acid fast stain, fungal stain and culture, and cytomegalovirus polymerase chain reaction (PCR) test. Computed tomography (CT) of chest, abdomen, and pelvis was unremarkable. Cerebral angiography was negative. A right frontal lobe stereotactic biopsy showed gliosis, but no specific findings. An electroencephalogram showed minimal background slowing. The patient developed further clinical deterioration, including worsening mentation. Images from repeat MRI are shown in Figure 2. The lesions were still nonenhancing (not shown).


(Enlarge Image)

Serial T2-weighted MRI scans performed 2 months apart; the latter were performed because of clinical deterioration (8 months after symptom onset). These latter images were taken after a right frontal biopsy, which caused the small right subdural effusion. Lesions are still non-enhancing (not shown). Reprinted with permission from Bakshi et al. Dementia and Geriatric Cognitive Disorders 1999;10:152-157

The repeat MRI shows that the lesions have:

1. 
   Improved
   
2. 
   Stabilized
   
3. 
   Worsened
   

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<p>Worsened</p>


Two weeks after the repeat MRI, the patient became comatose and was discharged to a chronic care facility, where he died shortly thereafter. Autopsy revealed a diffusely infiltrating focally necrotic process involving all regions of both cerebral hemispheres, cerebellum, and brainstem. Two patterns of cell proliferation were noted -- a typical angiocentric pattern in some regions, and a more infiltrative or "encephalitic" pattern in others. The disease showed typical plasmacytoid features and B-cell immunophenotype. Examination of the brain tissue by PCR was negative for varicella-zoster virus, Epstein-Barr virus, and cytomegalovirus DNA. The autopsy included only the brain.

The most likely diagnosis is:

1. 
   Primary CNS vasculitis
   
2. 
   Demyelinating disease
   
3. 
   Prion disease
   
4. 
   Primary CNS lymphoma
   
5. 
   Mitochondrial disease
   

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<p>Primary CNS lymphoma</p>