Familial meningocerebrovascular transthyretin

NEUROLOGY 1996;47:1562-1567 Systemic familial amyloidosis frequently affects the peripheral or central nervous system (CNS). In recent years, the molecular characterization of the various deposited amyloid proteins has resulted in a new classification of amyloid~ses.l-~ The most common clinical syndrome associated with transthyretin O"I!R) amyloid is polyneuropathy. We report here clinicopathologic features of a novel, extraordinary type of systemic familial transthyretin amyloidosis causing CNS disease in a Hungarian family. Uemichi et al.4 reported in 1992 a family of Hungarian descent living in the United States with mutant n ' R (ARG 101, but the disease was associated with familial polyneuropathy. Clinical and pathologic features of our patients show similarities to oculoleptomeningeal familial amyloidosis (OLMA)6-8 but were different in several respects. Case reports. Family history. Early in 1991, a middleaged woman was admitted to our neurological department with temporary disorientation. CTs showed symmetric calcification of the cortex along the sylvian fissure. The cerebrospinal fluid (CSF) protein level was markedly increased. Three years earlier, the CT of a female patient with a similar high CSF protein level disclosed the same change. They were first cousins, and the father of one and an uncle of both patients had died in our department many years before and had undergone autopsy. New histologic sections were made from stored paraffin blocks and examined. In the interval, the first of our female patients died; histology showed systemic amyloidosis. Compilation of the family history resulted in a pedigree (figure 1) that covers 56 persons in four generations. Most members of this family had lived for a long time in the surroundings of Szombathely, Hungary. He was admitted to the neurological department six times between 1938 (at the age of 36) and 1960. On each admission, he complained of severe headache, nausea, and vomiting, sometimes with transitory diplopia. At first admission, there was partial loss of hearing in his left ear. Best corrected visual acuities were 20130. The patient had severe myopia (-5.0 dpt) and astigmatism. At repeated examinations, no alterations on the cornea or in the fundus were found. He developed vertical nystagmus, limb and trunk ataxia, intentional tremor, hyperreflexia and pyramidal signs, and, later, urinary retention and constipation. He became confused during an attack of severe headache. The CSF protein level was markedly increased (103 mg/dL D.03 &I) and rose to 330 mg/dL (3.30 g/L) by the end of his illness. The lateral ventricles, the third ventriPatient 1 (IZ-6 in figure 1). From the Departments of Neurology (Dr. Garzuly) and Pathology (Dr. Brittig), Markusovszky Hospital, Szombathely, Hungary; the Department of Neurology (Dr. Wisniewski), New York University Medical Center, New York, Ny; and the Institute of Neurology (Dr. Budka), University of Vienna, Vienna, Austria. T.W. is supported by National Institute of Health grants AGO0542 and AGO8721. Received March 4, 1996. Accepted in final form May 3, 1996. Address correspondence and reprint requests to Dr. Herbert Budka, Institute of Neurology, University of Vienna, Wahringer Giirtel 18-20, POB 48, A-1097 Wien, Austria. 1662 Copyright