cqvip:Objectives: To report the clinical features of two Japanese brothers with fami lial leptomeningeal amyloidosis, showing a causative gene abnormality of a trans thyretin (TTR) variant Asp18Gly, previously reported only in a Hungarian family. Methods: The authors reported on a 42 year old man (patient 1) and his 45 year o ld brother (patient 2), both suffering from subarachnoid haemorrhage (SAH) witho ut and with hydrocephalus, respectively. DNA sequences of the TTR gene were dete rmined in both patients and the patientsclinical features described. A surgica l biopsy of the leptomeninges was performed on patient 1. Results: DNA sequence analyses demonstrated the glycine for aspartate substitution at position 18 of the TTR variant. Both patients revealed pyramidal tract signs and cerebellar at axia. Audiometric studies showed bilateral, mild sensori neural hearing loss in the patients whose cerebrospinal fluid (CSF) protein levels increased. T1 weigh ted MRI after contrast administration showed diffuse leptomeningeal enhancement along the Sylvian fissures and over the surface of the brainstem, cerebellum, an d spinal cord. Gradient echo T2.weighted MRI showed superficial siderosis mainly in the cerebellum. A biopsy of the leptomeninges was obtained from the spinal c ord of patient 1. While performing the biopsy, the authors observed the varicose , elongating, and fragile veins on the dorsal surface of the spinal cord. Immuno histochemical study revealed marked deposits of TTR derived amyloid on his lepto meninges. Conclusions: This is the second report of familial leptomeningeal amyl oidosis with an Asp18Gly TTRgene mutation, clinically causing only CNS symptoms. Repeated SAH from fragile veins on the dorsal surface of the spinal cord seemed to induce superficial siderosis of the CNS. So far, there have been two reliabl e hallmarks leading to the diagnosis of leptomeningeal amyloidosis: diffuse lept omeningeal enhancement on contrast MRI and greatly increased CSF protein content . This study has contributed a third hallmark: the presence of superficial sider osis is useful in diagnosing leptomeningeal amyloidosis.
展开▼
