Brett et al. (1999) described the case of a middle-aged woman with a leu12-to-pro (L12P) mutation of the TTR gene product, an extensive amyloid deposition in the leptomeninges and liver as well as the involvement of the heart and peripheral nervous system, typical of familial amyloid polyneuropathy caused by variant TTR (AMYLD1; 105210). Clinical features attributed to her leptomeningeal amyloid included radiculopathy, central hypoventilation, recurrent subarachnoid hemorrhage, depression, seizures, and periods of decreased consciousness. MRI showed a marked enhancement throughout her meninges and ependyma, and TTR amyloid deposition was confirmed by meningeal biopsy. The simultaneous presence of extensive visceral amyloid and clinically significant deposits affecting both peripheral and central nervous system extended the spectrum of amyloid-related disease associated with TTR mutations. Brett et al. (1999) suggested that leptomeningeal amyloidosis should be considered part of the syndrome of TTR-related familial amyloid polyneuropathy. Their index case was 38 years old when she first began to notice easy bruising. Five years later she began to get persistent headaches, and 6 months later presented with severe headache of sudden onset. CT and lumbar puncture confirmed subarachnoid blood, but angiograms showed no definite bleeding point. Two months later she had another subarachnoid bleed. About 4 years later, she started to notice hearing loss bilaterally, increasingly severe headaches, unsteadiness, urinary frequency, incomplete bladder emptying, and poor urinary stream. A CT scan showed hydrocephalus; insertion of a right lateral ventriculoperitoneal shunt was complicated by a small subdural hematoma. After the shunt, her unsteadiness and urinary symptoms partially improved. After a complicated and distressing course the patient died at the age of 53 years. The family history showed that the mother had committed suicide at the age of 62 after 2 years of depression and physical illness that included urinary symptoms, constipation, and falls. However, histologic study of sections of heart, lung, and kidney from the mother's postmortem material showed no amyloid.
