Development of gastrointestinal beta2-microglobulin amyloidosis correlates with time on dialysis

Dialysis-associated beta2-microglobulin (beta2m) amyloidosis affects predominantly musculoskeletal tissue, but visceral involvement also occurs. To evaluate the clinical significance and prevalence of gastrointestinal beta2m amyloidosis, we studied hemodialysis patients admitted for gastrointestinal-related complaints. Hemodialysis patients (excluding those with non-beta2m amyloidosis) who were admitted with gastrointestinal complaints from 1984 to 1994 were identified. Gastrointestinal tissues from patients with available autopsy or surgical specimens were examined using hematoxylin and eosin stain, Congo red stain, and beta2m immunostain. Each case was evaluated independently by two pathologists and scored for quantity and location of beta2m amyloid and associated pathology. Of 24 patients, eight (four men and 4 women) had beta2m amyloid deposits within the gastrointestinal tract. Acute clinical presentation ranged from abdominal pain to gastrointestinal bleeding and was not significantly different for patients with or without gastrointestinal beta2m amyloid deposits. However, the mean time on dialysis of 15.3 +/- 5.7 years (range 6-24 years) for patients with gastrointestinal beta2m amyloidosis was significantly greater than that of patients without gastrointestinal beta2m amyloidosis (10.5 +/- 7.0 years, range <1 to 22 years, p < 0.05). Vascular histopathology ranged from mild focal thickening of vessel walls to massive vascular beta2m amyloid deposition with thrombosis. Extravascular beta2m amyloid ranged from mild to severe with marked expansion of the submucosa. Mucosal pathology ranged from none to severe ulceration. The degree of beta2m amyloid and the associated pathology tended to increase in severity with time on dialysis. Gastrointestinal beta2m amyloid deposition is an underappreciated complication of chronic hemodialysis that is significantly associated with increased time on dialysis. Gastrointestinal beta2m amyloidosis should be considered in any patient on hemodialysis 10 years or more who has gastrointestinal symptoms and can be identified in resection specimens as well as some biopsy specimens. Congo red stain and beta2m immunostains may be necessary for sensitive histopathologic evaluation of gastrointestinal beta2m amyloidosis.     

Serum amyloid P component scintigraphy in familial amyloid polyneuropathy: regression of visceral amyloid following liver transplantation

Familial amyloid polyneuropathy (FAP) associated with transthyretin (TTR) mutations is the commonest type of hereditary amyloidosis. Plasma TTR is produced almost exclusively in the liver and orthotopic liver transplantation is the only available treatment, although the clinical outcome varies. Serum amyloid P component (SAP) scintigraphy is a method for identifying and quantitatively monitoring amyloid deposits in vivo, but it has not previously been used to study the outcome of visceral amyloid deposits in FAP following liver transplantation. Whole body scintigraphy following injection of iodine-123 labelled SAP was performed in 17 patients with FAP associated with TTR Met30 and in five asymptomatic gene carriers. Follow-up studies were performed in ten patients, eight of whom had undergone orthotopic liver transplantation 1-5 years beforehand. There was abnormal uptake of 123I-SAP in all FAP patients, including the kidneys in each case, the spleen in five cases and the adrenal glands in three cases. Renal amyloid deposits were also present in three of the asymptomatic carriers. Follow-up studies 1-5 years after liver transplantation showed that there had been substantial regression of the visceral amyloid deposits in two patients and modest improvement in three cases. The amyloid deposits were unchanged in two patients. In conclusion, 123I-SAP scintigraphy identified unsuspected visceral amyloid in each patient with FAP due to TTR Met30. The universal presence of renal amyloid probably underlies the high frequency of renal failure that occurs in FAP following liver transplantation. The variable capacity of patients to mobilise amyloid deposits following liver transplantation may contribute to their long-term clinical outcome.     

Familial amyloidotic polyneuropathy type I with extracellular superoxide dismutase mutation: a case report

We report an autopsy case of familial amyloidotic polyneuropathy (FAP) Type I with mutations in both transthyretin (TTR) and extracellular superoxide dismutase (EC-SOD). This patient started to develop peripheral neuropathy at age 25, followed by cardiac, renal, and autonomic nervous system failure due to massive amyloid deposition. Thirteen years after the initial symptoms, he died of septic shock. Autopsy revealed suppurative peritonitis, multiple abscesses in the bile ducts and urinary tract, and more marked amyloid deposition than commonly seen in FAP. Amyloid deposition occurred in various organs and tissues, especially prominently around blood vessels and in interstitial tissues, and was demonstrated immunohistochemically to be composed of TTR but not amyloid A (AA) and not amyloid L (AL) proteins. The serum EC-SOD content of the patient was 10 fold higher than those seen often in other FAP patients and in healthy controls. Genetic analysis demonstrated the single amino acid substitutions in Val30Met TIR and Arg213Gly EC-SOD. Since these data suggest the dissociation of EC-SOD from the vascular wall, massive amyloid deposition in the present case may be related to increased oxidative stress in loco.     

Amyloidosis secondary to rheumatoid arthritis associated with plexiform change in bilateral temporal lobes

A 70-year-old woman with rheumatoid arthritis (RA) and secondary amyloidosis presented repeated consciousness loss. The pathological findings at autopsy revealed multi-organic deposits of amyloid A-protein and so-called 'plexiform change' of blood vessels in bilateral temporal lobes. The arterial plexiform change, which is found in the lung specimen of primary pulmonary hypertension, might be a new pathological cerebrovascular change associated with RA.     

Glycogenolysis stimulation by non-steroidal anti-inflammatories in the perfused rat liver is not accompanied by Ca2+ release

To better understand the characteristics of amyloid deposition in the choroid plexus, we examined autopsied brain by routine histology, immunohistochemistry, and electron microscopy in three group of patients: primary systemic amyloidosis (n = 7), cerebral amyloid angiopathy (CAA, n = 6), and controls (n = 3). Three of the CAA patients had Alzheimer's disease. Congophilic, birefringent amyloid deposits of the choroid plexus were seen in six of the seven cases of systemic light chain amyloidosis. Immunohistochemistry revealed that the deposited amyloids had reactivity for immunoglobulin light chain and amyloid P component. Accumulation of macrophages labeled with monoclonal antibodies against CD 68 and major histocompatibility complex class II antigens were observed around the massive amyloid deposits. The presence of approximately 10 nm amyloid fibrils along the epithelial basement membrane as well as in the vascular walls was ascertained by electron microscopy. In CAA, Congo red-positive amyloid deposits were consistently present in meningeal blood vessels and were often found in senile plaques of the cerebral parenchyma; congophilic amyloid deposits were absent in the choroid plexus. Choroid plexus epithelial cells exhibited immunostaining for beta amyloid precursor protein (APP) with N-terminal- and C-terminal-specific antibodies; in particular, consistent staining was obtained for the latter antibody. Immunoreactivity for amyloid beta protein (A beta) with monoclonal antibodies (6E10, 4G8) was often found in choroid plexus epithelial cells. These findings suggest that amyloid deposition of the choroid plexus depends on the major component protein in amyloidosis, and that the choroid plexus may produce APP and A beta protein although A beta amyloidosis is not evident in the choroid plexus.     

Primary amyloidosis--involving principally intrarenal blood vessels

We analysed renal biopsies from 34 nephrotic patients with renal amyloidosis, seven with primary form kappa chain (AL amyloidosis) and 27 with secondary amyloidosis associated with the other chronic diseases. Renal biopsy specimens were analysed using optical and immunofluorescence microscopy. The extent of amyloid deposits was graded from 0 to + + + +. Intrarenal blood vessel deposits were more prominent than intraglomerular in five of seven patients with AL amyloidosis, while they were identical in one, and in one, intraglomerular amyloid deposits were dominant. The results were different in the group of patients with secondary amyloidosis: a lower degree of intrarenal blood vessels deposition than glomerular was noted in 22 of 27 cases, the degree of deposition was identical in 4 of 27 cases and more expressed blood vessel deposition was present in only one case. Granular or combined deposits (granular+linear) were found on immunofluorescence microscopy in primary form, but the dominant form of deposition was amorphous in secondary amyloid.     

Skin involvement in amyotrophic lateral sclerosis

BACKGROUND: Patients with sporadic amyotrophic lateral sclerosis (ALS) show disorganised collagen and elastin of the dermis. We looked for inflammatory alterations to cutaneous blood vessels. PATIENTS AND FINDINGS: Seven patients with sporadic ALS were investigated; five were confined to bed, but none had bedsores. Light and electron microscopy of skin showed an oedematous dermis with collagen fibrils of irregular diameter. Small blood vessels were characterised by duplicated basement membranes and deposition of beta-amyloid protein, the main component of the neuronal and non-neuronal amyloid deposits in Alzheimer's disease. These skin changes were seen in all degrees of disability, but none was found in age-matched and sex-matched controls. INTERPRETATION: The skin in ALS is characterised by a distinctive pattern of alterations of connective tissue and blood vessels. Examination of skin in an additional and easily accessible investigation which may help elucidate the pathogenesis of ALS.     

Response of therapy-related myelodysplasia to low-dose interleukin-2

A 66-year-old woman presented a spastic quadriparesis due to compression of the cervical cord 6 years after the beginning of chronic hemodialysis. Five years later, she developed a second episode of compressive myelopathy affecting the lumbar spine. On both occasions, surgical laminectomy with removal of fibroligamentous rings that compressed the cord led to a total recovery of the patient. Histological study demonstrated the presence of massive amyloid deposits in the surgically excised material.     

Prevalence of hepatitis C virus antibody in patients on chronic hemodialysis

Hepatitis C virus antibody (anti-HCV) was studied in 267 patients undergoing maintenance hemodialysis using an anti-HCV enzyme-linked immunosorbent assay. Furthermore, both hepatitis B virus core antibody (anti-HBc) and human T cell leukemia virus type 1 antibody (anti-HTLV-1) were determined in these patients to compare their prevalence rates. Seventy one patients (27%) had positive anti-HCV, 134 patients (50%) positive anti-HBc and 40 patients (15%) positive anti-HTVL-1. Among the 183 patients who had received blood transfusion, the prevalence of these antibodies was 34% for anti-HCV, 56% for anti-HBc and 17% for anti-HTLV-1, respectively. A significance between those with and without blood transfusion was recognized for anti-HCV (p < 0.001) and anti-HBc (p < 0.01). Of 56 patients who had received hemodialysis for over 15 years, the positive antibody was found in 63% for anti-HCV (p < 0.001), 73% for anti-HBc (p < 0.001) and 25% for anti-HTLV-1 (p < 0.05), which was significantly higher than that of patients receiving a less than 15 years hemodialysis. The prevalence rates of anti-HCV and anti-HTLV-1 did not increase with age, while that of anti-HBc increased. These findings suggest that blood transfusions during hemodialysis play a very important role in the infection of hepatitis C virus.     

Is the "preamyloid" of diffuse plaques in Alzheimer's disease really nonfibrillar?

Several papers have described an 'amorphous' component of the amyloid in diffuse plaques and it has been suggested that this is 'preamyloid,' which is not organized into fibrils. Because most of the studies have been performed on autopsy tissue it was the purpose of this study to compare the ultrastructure of diffuse amyloid deposits in well preserved Alzheimer's disease biopsy specimens with autopsy tissues from patients with Alzheimer's disease and Down's syndrome. A postembedding immunogold technique with anti-beta/A4 protein demonstrated gold particles exclusively on extracellular amyloid fibrils in both biopsy and autopsy brains. We have presented evidence that suggests the claim for the existence of an amorphous component within the beta/A4 protein-positive material is unconvincing.     

Identification of pentosidine as a native structure for advanced glycation end products in beta-2-microglobulin-containing amyloid fibrils in patients with dialysis-related amyloidosis

beta-2-Microglobulin (beta-2m) is a major constituent of amyloid fibrils in patients with dialysis-related amyloidosis (DRA). Recently, we found that the pigmented and fluorescent adducts formed nonenzymatically between sugar and protein, known as advanced glycation end products (AGEs), were present in beta-2m-containing amyloid fibrils, suggesting the possible involvement of AGE-modified beta-2m in bone and joint destruction in DRA. As an extension of our search for the native structure of AGEs in beta-2m of patients with DRA, the present study focused on pentosidine, a fluorescent cross-linked glycoxidation product. Determination by both HPLC assay and competitive ELISA demonstrated a significant amount of pentosidine in amyloid-fibril beta-2m from long-term hemodialysis patients with DRA, and the acidic isoform of beta-2m in the serum and urine of hemodialysis patients. A further immunohistochemical study revealed the positive immunostaining for pentosidine and immunoreactive AGEs and beta-2m in macrophage-infiltrated amyloid deposits of long-term hemodialysis patients with DRA. These findings implicate a potential link of glycoxidation products in long-lived beta-2m-containing amyloid fibrils to the pathogenesis of DRA.     

Myopathy in primary systemic amyloidosis

OBJECTIVE: To define the natural history of primary systemic amyloidosis when muscle involvement is prominent at presentation. METHODS: A retrospective review was carried out of all patients seen at the tertiary referral practice of the Mayo Clinic between 1 January 1960 and 31 December 1994. All patients with primary systemic amyloidosis and proof of amyloid deposits by muscle biopsy were included for analysis. No patients were lost to follow up. RESULTS: Twelve patients were identified with amyloidosis in muscle. Muscle involvement was the most prominent symptom in patients who had widespread visceral involvement, which included the heart, peripheral nerve, and tongue. Of the 12, three had skeletal muscle pseudohypertrophy. All patients had a demonstrable dysproteinaemia by the finding of free light chain in the serum or urine, a discrete monoclonal peak on serum or urine protein electrophoresis, or a monoclonal population of plasma cells in the bone marrow. Measurement of creatine kinase was not a useful test. Of eight patients treated with chemotherapy based on alkylating agents, three responded. The median survival for the entire group was 12 months. CONCLUSIONS: The finding of a monoclonal protein in a patient with muscle weakness is an important clue to the diagnosis of primary systemic amyloidosis. Most patients have visceral involvement outside the musculoskeletal system. A subset of patients seems to respond to systemic chemotherapy. The overall survival, however, remains poor, with most patients dying of cardiac failure. Immunoelectrophoresis of serum and urine should be a routine diagnostic test during the evaluation of myopathy of unknown cause.     

Domino hepatic transplantation using the liver from a patient with familial amyloid polyneuropathy

BACKGROUND: In transplantation, novel methods are required to augment the supply of donor organs. We report the first domino liver transplant in which a patient with familial amyloid polyneuropathy (FAP) received an orthotopic split liver graft, and her explanted liver was donated to another patient. Three successful liver transplants were thus achieved from the one cadaver liver. PATIENTS AND METHODS: A cadaveric donor liver was split and the left lobe was grafted into a child with biliary atresia. The right lobe was transplanted into a woman with FAP associated with the transthyretin Met30 variant. Her own otherwise healthy liver was donated to a patient with cirrhosis and hepatocellular carcinoma. RESULTS: Fifteen months after transplantation, all three recipients are well with normal liver function. The domino recipient developed inferior vena cava stricturing at the level of anastomosis after surgery with resultant ascites, requiring dilatation and LeVeen shunt insertion. Serum amyloid P component scintigraphy showed amyloid regression in the domino donor and to date has not identified any amyloid deposits in the recipient, who also remains free of tumor recurrence. CONCLUSIONS: Domino transplantation using the livers from patients with FAP may be justified for patients whose disease condition precludes a long spell on the waiting list, including those with hepatic malignancies and those for whom palliation rather than long-term cure is the aim.     

N epsilon-(carboxymethyl)lysine in blood from maintenance hemodialysis patients may contribute to dialysis-related amyloidosis

BACKGROUND: Recent studies demonstrated not only that advanced glycation end product could be found in amyloid tissue from patient with dialysis related amyloidosis, but also that amyloid beta2-microglobulin was modified with N(epsilon)-(carboxymethyl)lysine (CML). We wanted to determine if CML could be a biomarker in these patients. METHODS: To raise polyclonal anti-carboxymethyllysine antibody, human serum albumin was carboxymethylated by glyoxylic acid and was immunized to rabbits as antigen. Carboxymethyllysine-hemoglobin (CML-Hb) levels were measured by the dot blotting method using this antibody. RESULTS: The levels of CML-Hb were 6.68 +/- 3.10 nmol CML/mg Hb in nondiabetic hemodialysis patients (N = 70), 6.39 +/- 3.43 nmol CML/mg Hb in diabetic hemodialysis patient (N = 21), and 3.13 +/- 0.88 nmol CML/mg Hb in 47 healthy volunteers. For clinical signs of dialysis-related amyloidosis, 70 nondiabetic hemodialysis patients were scored according Gejyo's criteria. The CML-Hb levels in patients with a high amyloid score as well as a low amyloid score were significantly higher than in patients with negative amyloid score (8.89 +/- 3.53 nmol CMLmg Hb, 7.28 +/- 2.32 nmol CML/mg Hb vs. 5.11 +/- 2.09 nmol CML/mg Hb, P < 0.001, P < 0.05). Furthermore, the CML-Hb levels correlated significantly with serum values of the methylguanidine over creatinine ratio and hyaluronate. CONCLUSIONS: We suggest that CML-Hb is increased in blood from patients on maintenance hemodialysis and is thus a potential biomarker of oxidative damage in these patients. Moreover, CML-modification of protein may play a pathogenic role in the development of dialysis related amyloidosis.     

Amyloid and non-amyloid carpal tunnel syndrome in patients receiving chronic renal dialysis

OBJECTIVE: To determine the prevalence of amyloid deposits among patients with carpal tunnel syndrome (CTS) receiving dialysis, and to investigate the factors associated with amyloid and non-amyloid CTS. METHODS: Subjects for this prospective study were dialysis patients who underwent surgery for CTS in the same surgical unit between 1989 and 1997. CTS was diagnosed from clinical and electromyographic (EMG) findings. Systematic standard radiographs and laboratory data were also obtained. Surgical investigations included systematic macroscopic examination and biopsy of the epineurium, flexor retinaculum, synovium, and flexor tendon sheaths. Samples were stained for amyloid and examined by plain and polarized light microscopy, immunohistochemistry, and electron microscopy. RESULTS: Forty-one samples from 30 patients (11 bilateral cases) were examined. Amyloid deposits were found in 26 samples from 18 patients (7 M, 11 F). Fifteen samples from 12 patients (3 M, 9 F) showed no amyloid deposits. Amyloid CTS was statistically significantly associated with arthralgia and longterm dialysis [mean 13.3 (range 5.5-23) vs 7.5 yrs (range 3 mo-14 yrs)] in non-amyloid CTS. Flexor tenosynovitis and carpal bone erosion occurred more frequently in amyloid CTS. There were no statistically significant differences between the 2 groups in clinical, laboratory or EMG findings, type of dialysis membrane, or frequency of ipsilateral fistula. Only amyloid CTS was recurrent. CONCLUSION: Amyloid deposits were confirmed microscopically in 63.4% of patients. The relatively large number of cases of non-amyloid CTS without signs of dialysis associated arthropathy suggests that CTS is not a satisfactory criterion for diagnosis of dialysis arthropathy or beta2-microglobulin amyloidosis unless the presence of amyloid has been confirmed or duration of dialysis treatment has been at least 15 years.     

Determination of the frequency and distribution of vascular and parenchymal amyloid with polyclonal and N-terminal-specific PrP antibodies in scrapie-affected sheep and mice

Brains from 17 histopathologically confirmed cases of scrapie, five of which had congophilic vascular amyloid, were stained immunohistochemically for prion protein (PrP) using a polyclonal antibody. Two clinically suspect but pathologically unconfirmed cases of natural sheep scrapie and the brains of four mice infected with the 111A murine scrapie strain were also examined. Selected sections containing amyloid were stained with each of two peptide antibodies which recognise the N-terminal amino acid residues which are lost following protease digestion of the disease-specific isoform of PrP. The mice infected with the 111A murine scrapie strain had large numbers of hypermature plaques. All the amyloid plaques from both natural sheep scrapie brains and experimental murine brains were heavily immunostained by the polyclonal and both peptide antibodies. In addition, disease-specific accumulations of PrP were detected in endothelial cells or in the intima of blood vessels of the cerebral cortex of sheep scrapie brains. The affected blood vessels were located in areas which otherwise lacked typical scrapie pathology. Vascular accumulations of PrP were also found in leptomeningeal and choroid plexus blood vessels. Vascular amyloid was found mainly in the neocortex. Vascular amyloid and disease-specific parenchymal accumulations of PrP were found in two sheep which showed clinical signs of scrapie but lacked its typical vacuolar pathology. These results show that the mature amyloid of scrapie is composed of, or contains a substantial proportion of, whole length PrP protein. Thus truncation of PrP is not essential for the aggregation of PrP into amyloid. The vascular amyloid of natural sheep scrapie originates from the accumulation and release of PrP from endothelial cells presumably following systemic scrapie infection. The topography of vascular amyloid distribution in Great Britain differs from that reported in the Netherlands. As amyloid deposition in mice is largely controlled by the strain of the infecting agent it is possible that the strain of the agent may influence vascular amyloid deposition.     

Amyloid arthropathy of the hip joint: MR demonstration of presumed amyloid lesions in 152 patients with long-term hemodialysis

The aim of this study was to determine the spectrum of MR findings of presumed amyloid arthropathy of the hip joints in patients on long-term hemodialysis. We prospectively performed T1- and T2-weighted spin-echo imaging on 152 consecutive patients on hemodialysis. The duration of hemodialysis ranged from 5 months to 24 years, 2 months (mean: 8 years, 8 months). The frequency, location, and signal intensity of bone lesions were assessed. In 12 cases with contrast-enhanced MR examination, enhancement pattern of bone lesions, synovial lesions, and intra-articular lesions were characterized. Bone lesions presumed to be amyloid deposits were identified in 60 patients (39%). Magnetic resonance imaging revealed that amyloid lesions were more extensive than anticipated by plain radiographs. All bone lesions showed decreased signal intensity on T1-weighted images. On T2-weighted images, bone lesions showed increased signal intensity in 32 patients (54%), decreased signal intensity in 11 patients (18%), and both increased and decreased signal intensity in 17 patients (28%). Following intravenous injection of gadolinium-based contrast, all bone lesions showed moderate enhancement. Synovial thickening could not be identified on T1- and T2-weighted images. However, contrast-enhanced images showed thickened synovial membrane, which could be differentiated from joint fluid. Intra-articular nodules showed decreased or intermediate signal intensity on T1-weighted images and decreased signal intensity on T2-weighted images; the intra-articular nodules were contiguous with subchondral bone lesions. Magnetic resonance imaging is useful for evaluating the distribution and extent of amyloidosis of the hip joints in patients undergoing long-term hemodialysis.     

Diagnosis and treatment of postoperative chyle leakage via percutaneous transabdominal catheterization of the cisterna chyli: a preliminary study

BACKGROUND AND AIMS: The liver is frequently involved in amyloidosis but the significance of hepatic amyloid has not been systematically studied. We have previously developed scintigraphy with 123I serum amyloid P component (123I-SAP) to identify and monitor amyloid deposits quantitatively in vivo and we report here our findings in hepatic amyloidosis. METHODS: Between 1988 and 1995, 805 patients with clinically suspected or biopsy proven systemic amyloidosis were evaluated. One hundred and thirty eight patients had AA amyloidosis, 180 had AL amyloidosis, 99 had hereditary amyloid syndromes, and 67 had dialysis related (beta 2 microglobulin) amyloid. One hundred and ninety two patients with amyloidosis were followed for six months to eight years. RESULTS: Hepatic amyloid was found in 98/180 (54%) AL and 25/138 (18%) AA patients but in only 1/53 patients with familial transthyretin amyloid polyneuropathy and in none with dialysis related amyloidosis. There was complete concordance between hepatic SAP scintigraphy and the presence or absence of parenchymal amyloid deposits on liver histology. Amyloidosis was never confined to the liver. Mortality was rarely due to hepatic failure, although hepatic involvement with AA amyloid carried a poor prognosis. Successful therapy to reduce the supply of amyloid fibril protein precursors was followed by substantial regression of all types of amyloid. CONCLUSIONS: SAP scintigraphy is a specific and sensitive method for detecting and monitoring hepatic amyloid. Liver involvement is always associated with major amyloid in other organ systems and carries a poor prognosis in AA type. Appropriate therapy may substantially improve prognosis in many patients.     

Cerebral amyloid angiopathy

Cerebral amyloid angiopathy affects the cerebral vasculature selectively, and there is no systemic amyloidosis. Amyloid is deposited in small and medium-sized vessels of the cortex and leptomeninges. Cerebral amyloid angiopathy is a common cause of spontaneous lobar haemorrhage in elderly patients. However, cerebral amyloid angiopathy may have atypical clinical and radiological presentations. We report on five patients (three males and two females, aged 43-77 years) with histologically verified cerebral amyloid angiopathy. One patient experienced an acute headache attack and classical lobar haemorrhage. The other patients had various neurological symptoms and signs, such as seizure, disturbed vision, pareses, aphasia, and dementia that were initially diagnosed as cerebral infarction or tumour. Two patients with cerebral amyloid angiopathy and granulomatous angiitis responded to immunosuppressive treatment.     

Alzheimer-type lesions in Huntington's disease

Cognitive changes in Huntington's disease (HD) are variously related to diffuse cortical atrophy with neuron loss and dystrophic neurites leading to disruption of striato-frontal or limbic circuitries, while recent studies suggest an increasing prevalence of Alzheimer-like lesions in HD brain. A comparative morphological study of 27 autopsy cases of HD (age 34 to 75 years) and of 26 age- and sex-matched non-demented controls was performed. Absence of Alzheimer-type lesions was seen in 33% of HD brains (mean age 49 years); 48% showed early non-neuritic tau pathology in limbic areas (Braak stages I and II) without amyloid deposits occurring as early as age 34 years (mean age 54 years), while Braak stages II and III with amyloid plaques were present in 19%, the youngest such HD patient being 42 years (mean age 54 years). In controls, similar tau pathology changes with later onset (age 45 years) and occurrence of amyloid plaques in 26%--all aged over 60 years--were observed. No probable or definite cases of Alzheimer disease (AD) according to CERAD criteria were seen in both cohorts. Those data confirm previous studies on the rare coexistence of HD and AD, although initial stages of Alzheimer-like lesions develop rather early in HD patients, but obviously show less rapid progress even in advanced age. The reasons for the early onset but mild progress of Alzheimer-like lesions in HD and their contribution to cognitive decline await further elucidation.