Progressive dementia and leucoencephalopathy as the initial presentation of late onset hereditary cystatin-C amyloidosis Clinicopathological presentation of two cases

• Published in: Journal of the neurological sciences Vol. 140; no. 1; pp. 101 - 108
• Main Authors: Sveinbjörnsdóttir, Sigurlaug, Blöndal, Hannes, Gudmundsson, Gretar, Kjartansson, Ólafur, Jónsdóttir, Sif, Gudmundsson, Gunnar
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 01-09-1996; Elsevier Science
• Subjects: Aged; Amyloid; Amyloid beta-Peptides - metabolism; Amyloidosis - genetics; Amyloidosis - metabolism; Amyloidosis - pathology; Angiopathy; Biological and medical sciences; Brain - pathology; Cerebral hemorrhages; Cystatin C; Cystatins - metabolism; Cysteine Proteinase Inhibitors - metabolism; Dementia; Dementia - pathology; Demyelinating Diseases - pathology; Errors of metabolism; Female; HCCA; HCHWA; Hereditary; Humans; Male; Medical sciences; Metabolic diseases; Middle Aged; Proteins and glycoproteins; HCHWA; Angiopathy; Cerebral hemorrhages; HCCA; Amyloid; Hereditary; Dementia; Human; Nervous system diseases; Pathogenesis; Metabolic diseases; Enzymopathy; Cerebral disorder; Genetic disease; Case study; Proteins; Symptomatology; Central nervous system disease; Amyloidosis
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/0022-510X(96)00094-9

Hereditary Cystatin-C Amyloidosis (HCCA) is a genetic disorder in Icelandic families in which a defective cystatin-C amyloid protein is deposited in the walls of small and middle sized arteries. Cerebral vessels are most affected, resulting in recurrent cerebral hemorrhages and infarctions, usually with onset of clinical symptoms in the twenties or thirties and a rapidly deteriorating clinical course. The disease can be diagnosed by a skin biopsy in symptomatic patients. We report two patients (father and daughter) who did not have a known family history of the disorder and presented late in life with a progressive dementia, associated with cerebral hemorrhages in the younger patient. Cerebral MRI and CT scans of this patient showed extensive leukoencephalopathic changes. Brain tissue samples from both patients showed immunohistochemical reaction to cystatin-C in small and medium-sized cerebral arteries and extensive cortical and white matter microinfarctions. The amyloid changes were less severe in the older patient and a colocation of β-amyloid protein and cystatin-C was observed in addition to neurofibrillary tangles and senile plaques. Subcortical and cortical infarctions were also observed. HCCA may present late in life with progressive dementia as the only clinical manifestation, reflecting a multi-infarct syndrome secondary to the amyloidosis. A coexpression of cystatin-C and beta protein may occur as in other cerebral amyloid disorders, probably as age-specific changes.