A 75-year-old woman was referred in acute care for mental deterioration, gait disorder, urinal incontinence, and unusual headache progressing over the six months. The family reported that the short-term memory loss gradually developed over the last two years. The daily activity was disturbed and required the presence of a caregiver. The past medical history included hypertension treated with atenolol. The medical family history was unremarkable.
On admission, the patient was bedridden. Neurological examination revealed a fluctuation of vigilance. She was mute and had a bilateral grasp reflex. There was no motor or sensory deficit. General physical examination was normal. Blood pressure was 150/70 mmHg and temperature was 37  C. Complete blood count, liver enzymes and serum electrolytes were normal. The results of blood inflammatory test were as follows: erythrocyte sedimentation rate 35 mm/hour, C-reactive protein 620 mg/dL (normal < 100), fibrinogen 51 mg/dL (normal < 40). Serum protein electrophoresis and immunoelectrophoresis were normal. To rule out a diagnosis of meningitis, a lumbar puncture was performed, yielding a clear cerebral spinal fluid (CSF) with 78 erythrocytes/mL, 2 leukocytes/mL, 250 mg/dL protein (normal < 45) with 14.6% IgG in a polyclonal pattern (normal < 10), and 63 mg/dL glucose (normal < 75). Bacterial examination of the CSF did not show any germ and cultures were negative. All serum and CSF tests for infection were unremarkable, including herpes simplex virus, varicella zoster virus, human immunodeficiency virus types 1 and 2, cytomegalovirus, mycoplasma pneumoniae, Lyme disease, syphilis, mycobacterium tuberculosis, and cryptococcosis. Brain computed tomography (CT) scan showed extensive hypointensities in the white matter in both hemispheres and a mild ventricular enlargement. There was no iodine fixation. Axial brain magnetic resonance imaging (MRI) showed T2-weighted high-intensities in the periventricular white matter and was negative in T1-weighted sequences with and without gadolinium infusion. On coronal images, the left hippocampus was atrophic. Search for antinuclear antibody was negative. Because of the severely disabled clinical status and the abnormality of the CSF, an intravenous corticotherapy was initiated seven day after admission with 120 mg dexamethasone per day associated with antibiotics. Vigilance and mutism improved in few days revealing a severe dementia with complete temporo-spatial disorientation. After three weeks of corticotherapy, CSF protein concentration was 46 mg/dL and C-reactive protein was normal. Brain CT scan was unchanged. The neurological status stabilized with a severe dementia. Corticosteroids were progressively tapered over the next five weeks and the patient was transferred to a geriatric rehabilitation hospital. She died four months later of a pulmonary infection.
On postmortem examination, the brain weighed 1180 g. Macroscopically, coronal brain slices showed a mild atrophy of the left hippocampus and a moderate enlargement of the lateral ventricles. The cortical band had a normal thickness. Focal small dark red infarcts were disseminated in the subcortical white matter of both hemispheres. The brainstem and cerebellum were normal. The circle of Willis was permeable. Samples of the hippocampus, entorrhinal cortex, middle frontal gyrus, superior and middle temporal gyri, inferior parietal lobule, and midbrain including the basal ganglia were fixed in 10% neutral-formalin and examined by light microscopy. On paraffin-embedded and hematoxylin-eosin-safran and congo red stained sections, lesions consisted in senile plaques, CAA, angiitis, and microinfarcts. Amyloid deposits were present in the neocortex of both cerebral lobes where they appeared as amorphous material in senile plaques. The wall of numerous vessels located in the leptomeningeal space and cortex were also infiltrated by these amyloid deposits. Inflammatory infiltrates consisting in lymphoid cells and macrophages surrounded both amyloid and non amyloid vessels in the leptomeningeal space and less frequently in the cortex (Figure 1A). There were neither multinucleated giant cells nor fibrinoid necrosis. In addition, numerous vessels including some with amyloid deposition showed severe intimal fibrosis occluding the lumen, and suggesting a post inflammatory healing process (Figure 1B). Multiple disseminated small infarcts were observed all over both hemispheres respecting the basal ganglia. They were filled with macrophages and surrounded by siderophages. Immunohistochemical study showed that amyloid deposits, present in the senile plaques and in the wall of vessels including some with an inflammatory infiltrate, were stained with betaA4 amyloid antigen (DAKO, Glostrup, Danemark) (Figure 1C, D). Tau (DAKO) immunolabeled the periphery of the majority of amyloid plaques, and defined neuritic plaques. Tau protein filamentous accumulation was present within the cells bodies of neurons indicating the presence of neurofibrillary tangles, especially in the isocortex (Figure 1E). A semiquantitative assessment of neocortical senile plaques density was estimated as superior to 17 per square millimeter in all the investigated samples of the neo-cortex. The density of neurofibrillary tangles was higher in the hippocampus and the entorrhinal cortex. In the myocardium, the wall of a coronary artery was infiltrated by lymphocytes, mononuclear cells, and giant multinucleated cells (Figure 1F). An interstitial fibrosis was present between the myocytes, likely due to hypertension. Vessel inflammatory changes were not found in the autopsy samples of lung, kidney, liver, spleen, and muscles examined by light microscopy.