Neuroradiologic and clinicopathologic features of oculoleptomeningeal type amyloidosis

Objective: To clarify the pathogenesis of leptomeningeal amyloidosis in familial amyloidotic polyneuropathy amyloidogenic transthyretin Y114C (FAP ATTR Y114C). Methods: The authors analyzed eight FAP ATTR Y114C patients. Six patients showed CNS symptoms associated with leptomeningeal amyloidosis. To examine the function of the blood-CSF barrier and blood-brain barrier (BBB), the authors performed CSF and MRI studies. The authors also performed a histopathologic study of autopsy specimens to examine the distribution of amyloid deposition in the CNS. Results: CSF study showed high total protein concentrations and increased albumin CSF/serum concentration quotients (Q(alb); an indication of blood-CSF barrier function). MRI with gadolinium (Gd) revealed enhancement from brainstem to spinal cord. Serial brain MRI studies with FLAIR images after Gd administration showed Gd leakage into the subarachnoid space (two patients). These findings suggested the blood-CSF barrier and BBB dysfunctions. Constructive interference in steady state (CISS) three-dimensional Fourier transformation (CISS-3DFT) sequence analysis demonstrated amyloid-induced funiculus structures joining the spinal cord and dura mater ( one patient). Histopathologic study revealed intense amyloid deposition in leptomeninges, vessel walls, and parenchyma in spinal cord and the brain. These distributions of amyloid deposition are unique compared to other TTR related leptomeningeal amyloidosis. Conclusions: Patients with familial amyloidotic polyneuropathy amyloidogenic transthyretin Y114C had CNS disorders related to amyloid deposition in leptomeninges, vessel walls, and parenchyma in spinal cord and the brain. The pathogenesis of CNS disorders may reflect disruption of the blood-CSF barrier and blood-brain barrier by amyloid deposition.