Incidence and prevalence of multiple system atrophy: a nationwide study in Iceland.

Background: Multiple system atrophy (MSA) is a neurodegenerative disorder characterised by autonomic dysfunction with parkinsonism (MSAp) or cerebellar (MSAc) symptoms. At autopsy, α-synuclein inclusions in glial cells of the brain are needed to confirm a definite diagnosis. We determined the 10 year incidence of MSA, point prevalence and survival in a well defined population with a high number of neurologists.

[Wernicke's encephalopathy in chronic alcoholics].

Wernicke's encephalopathy (WE) is caused by thiamine (vitamin B1) deficiency and most commonly found in individuals with chronic alcoholism and malnutrition. Clinically, its key features are mental status disorders and oculomotor abnormalities as well as stance and gait ataxia. The diagnosis of WE is frequently missed although delay of appropriate treatment can lead to death or Korsakoff's amnestic syndrome.

Solubilized cystatin C amyloid is cytotoxic to cultured human cerebrovascular smooth muscle cells.

Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid within arteries of the cerebral cortex and leptomeninges. This condition is age related, especially prevalent in Alzheimer's disease (AD) and the main feature of certain hereditary disorders. The vascular smooth muscle cells (VSMC) appear to play a vital role in the development of CAA and have been found to produce the amyloid beta precursor protein (AbetaPP) and process it to Abeta the major component of most CAA amyloid.

Risk of cancer among relatives of patients with glioma.

We report a population-based, retrospective study of 396 Icelandic people diagnosed with glioma in the years 1940-1995. The purpose of this study was to test whether astrocytomas, other glial tumors, other central nervous system tumors, or other cancers aggregate in families identified through glioma probands who were of Icelandic origin. Pedigrees of the 396 cases were traced by the Genetical Committee of the University of Iceland and linked to the Icelandic Cancer Registry.

The cerebral hemorrhage-producing cystatin C variant (L68Q) in extracellular fluids.

A variant of the normal extracellular cysteine protease inhibitor cystatin C (L68Q-cystatin C), is the amyloid precursor in hereditary cystatin C amyloid angiopathy (HCCAA). It has been suggested that the mutation causes cellular entrapment of L68Q-cystatin C in vivo and that the variant protein is not secreted to extracellular fluids. In order to test this hypothesis, we used matrix-assisted laser desorption ionization time-of-flight mass spectrometry in an effort to demonstrate the presence of L68Q- along with wildtype cystatin C in plasma and cerebrospinal fluid (CSF) of HCCAA-patients.

Progressive dementia and leucoencephalopathy as the initial presentation of late onset hereditary cystatin-C amyloidosis. Clinicopathological presentation of two cases.

Hereditary Cystatin-C Amyloidosis (HCCA) is a genetic disorder in Icelandic families in which a defective cystatin-C amyloid protein is deposited in the walls of small and middle sized arteries. Cerebral vessels are most affected, resulting in recurrent cerebral hemorrhages and infarctions, usually with onset of clinical symptoms in the twenties or thirties and a rapidly deteriorating clinical course. The disease can be diagnosed by a skin biopsy in symptomatic patients.

Presence of non-fibrillar amyloid beta protein in skin biopsies of Alzheimer's disease (AD), Down's syndrome and non-AD normal persons.

A total of 66 skin biopsies from persons with Alzheimer's disease (AD) or Down's syndrome (DS) and from persons without AD were used in this study. The age range was from 7 to 89 years. Positive immunoreactivity of skin biopsies to monoclonal antibody 4G8, which is reactive to amino acid residue 17-24 of synthetic amyloid beta protein (A beta), and 4G8-Fab (the antigen-binding fragment of 4G8 IgG, reactive only to amyloid plaque) was observed in the epidermis-dermis junction or the basement membrane of the epidermis and in some blood vessels of the biopsy skins of 13/18 (72%) AD, 9/10 (90%) DS, and 14/38 (37%) non-AD control cases.

Tumours in Iceland. 15. Ependymoma. A clinicopathological and immunohistological study.

Thirteen ependymomas reported to the Icelandic Cancer Registry during a 32-year period (1955-1986) were histologically reviewed and reclassified according to the WHO Histological Typing of Tumours of the Central Nervous System. The annual incidence rate of ependymoma was 0.20/100.

[Hereditary cerebral hemorrhage. Dementia with cystatin C amyloidosis].

Nineteen cases of hereditary cystatin C amyloidosis with cerebral haemorrhage are described. The first haemorrhage occurred between the ages of 20 and 41 years and the period of survival varied from 10 days to 23 years after the first insult. Progressive dementia was a striking clinical symptom in 17 of the patients and in two cases dementia was the first sign.

Skin deposits in hereditary cystatin C amyloidosis.

Clinically normal skin from 47 individuals aged 9-70 years was investigated. Cystatin C amyloid deposits were found in various locations of the skin by light and/or electron microscopy, in all 12 patients with a clinical history of hereditary cystatin C amyloidosis (HCCA). Six asymptomatic individuals, who had the Alu 1 restriction fragment length polymorphism (RFLP) marker reported to cosegregate with the disease, also had cystatin C amyloid deposits in the skin.

Dementia with non-hereditary cystatin C angiopathy.

Brain biopsies from two patients with non-hereditary cerebral hemorrhages and eighty autopsied cases with the clinical diagnosis of dementia are presented. The biopsied cases, both males aged 64 and 59, had a sudden onset of cerebral hemorrhage, mild progressive dementia and cystatin C cerebral amyloid angiopathy. Of the autopsied cases 59 had senile plaques and cerebral amyloid angiopathy was also found in 36 of them.

Dementia in hereditary cystatin C amyloidosis.

Nineteen cases with verified Hereditary Cystatin C Amyloid Angiopathy are presented. All of the cases had one or more cerebrovascular insults starting at the age of 20-41 years and survived from 10 days to 23 years after the first insult. Progressive dementia was a prominent clinical feature in seventeen cases of whom two presented with dementia.

Hereditary cystatin C (gamma-trace) amyloid angiopathy of the CNS causing cerebral hemorrhage.

Hereditary CNS amyloid angiopathy occurring in Icelanders is the first human disorder known to be caused by deposition of cystatin C amyloid fibrils in the walls of the brain arteries leading to single or or multiple strokes with fatal outcome. One or more affected members have been verified by histological examination in 8 families containing 127 affected. These originated from the same geographic area.

Immunohistochemical characterization of the amyloid deposits and quantitation of pertinent cerebrospinal fluid proteins in hereditary cerebral hemorrhage with amyloidosis.

Cystatin C, a protein inhibitor of lysosomal cysteine proteinases, was demonstrated by immunohistochemical techniques to be present in the birefringent amyloid deposits of the small arteries in the cerebrum, cerebellum, and leptomeninges of 10 Icelandic individuals with hereditary cerebral hemorrhage with amyloidosis. Specimens from other organs were investigated in one of the patients, and amyloid angiopathy characterized by an immunoreactivity of cystatin C was found in a submandibular lymph node. No immunoreactivity of amyloid fibril protein AA, kappa or lambda immunoglobulin light chain, or prealbumin was observed.

Serine derivative with antitumor activity.

The sodium salt of N-dichloroacetyl-DL-serine depresses the growth of sarcoma-37 in mice, causing complete regressions of the tumor. The compound is nontoxic to mice in doses up to 4 gm/kg of body weight. The animals do not lose body weight and show no alteration in the formed elements of the blood or in hemoglobin content.