Brain Pathology Case of the Month - February 2006

Contributed by Gianluigi Zanusso, MD, PhD1, Sergio Ferrari, MD1, Stefania Conte, MD2, Vittorio Mellina, MD 3
    Vittorio Sacchi, MD 4, Nicola Rizzuto, MD1, Salvatore Monaco, MD1
1 Section of Clinical Neurology, Department of Neurological and Visual Sciences, University of Verona, Verona, Italy.
2 Division of Neurology, Portoguaro, Venice. 3 Istituto Superiore di Sanità, Rome. 4 Division of Pathology, San Donà del Piave, Venice.


CLINICAL HISTORY:

A 44-year-old man with a four-year history of progressive neuropsychiatric symptoms, including irritability, apathy and hyposexuality, was admitted to another hospital because of increasing impairment of executive functions, delusions, paranoid ideation and mild cognitive decline. Physical and laboratory examinations were normal. An EEG study showed focal theta activity over the right frontal areas, whereas a brain MRI revealed mild cortical atrophy of the right hemisphere.

Gradual deterioration continued and four months later the patient was reported to have also impairment in visuospatial skills and in short-term memory. An EEG recording showed theta activity over the right frontotemporal region. MRI studies were unremarkable except for bilateral widening of cortical sulci.

At the age of 48 years neurological examination disclosed severe cognitive impairment, marked rigidity and hypokinesia. Axial proton density-weighted (Fig. 1A) and T2-weighted (Fig. 1B) MR images showed hyperintense signal in caudate heads, putamina and cortical ribbon, in addition to diffuse bilateral cortical widening. Over the next few months the patient became disoriented, akinetic and unable to feed. He died of gut occlusion nine years after the onset of the disorder.

GROSS AND MICROSCOPIC DESCRIPTION:

The brain was obtained at autopsy and divided in the midsagittal plane. The right half was fixed in formalin for neuropathological examination and the left half was frozen. Sectioning of the right brain revealed diffuse thinning of the cortical ribbon, especially in the frontal and temporal regions, with marked ventricular enlargement and white matter atrophy (Fig. 2A). The neostriatum, the thalamus and the amygdala were markedly affected, while the globus pallidus and the hippocampus were less involved (Fig. 2B). Pigmented nuclei appeared normal. The cerebellar cortex and white matter were atrophic.

Microscopic examination showed the neuropathologic changes as demonstrated in Figure 3. Figure 3A is from the frontal cortex, Figure 3B is from the hippocampus, and Figure 3C is from the cerebellum; Figure 3D depicts the granular layer of the cerebellar cortex and the inset shows a Congo-red stain. Additional studies were performed to confirm the diagnosis.

FINAL DIAGNOSIS



International Society of Neuropathology