Brain, Vol. 122, No. 2, 183-190,
February 1999
© 1999 Oxford University Press
Transthyretin Leu12Pro is associated with systemic, neuropathic and leptomeningeal amyloidosis
1 Neurology Department, MRC Cyclotron Unit, 2 Department of Immunological Medicine, Royal Postgraduate Medical School, Hammersmith Hospital and 3 Department of Clinical Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK
Correspondence to:
Dr Matthew Brett, MRC Cyclotron Unit, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK
We report a middle-aged woman with a novel transthyretin (TTR) variant, Leu12Pro. She had extensive amyloid deposition in the leptomeninges and liver as well as the involvement of the heart and peripheral nervous system which characterizes familial amyloid polyneuropathy caused by variant TTR. Clinical features attributed to her leptomeningeal amyloid included radiculopathy, central hypoventilation, recurrent subarachnoid haemorrhage, 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 the peripheral and central nervous system extends the spectrum of amyloid-related disease associated with TTR mutations. The unusual association of severe peripheral neuropathy with symptoms of leptomeningeal amyloid indicates that leptomeningeal amyloidosis should be considered part of the syndrome of TTR-related familial amyloid polyneuropathy.
familial amyloid polyneuropathy; oculoleptomeningeal amyloidosis; transthyretin
TTR = transthyretin
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