Clinicopathological and genetic features were assessed on 35 Japanese families affected by late-onset familial amyloid polyneuropathy type I (transthyretin Met30-associated familial amyloid polyneuropathy, FAP TTR Met30) whose siblings were unrelated to endemic Japanese foci. In these patients (50 years or older), the most common initial symptom was paraesthesias in the legs. Autonomic symptoms were generally mild and did not seriously affect daily activities. The male-to-female ratio was extremely high (10.7 : 1). A family history was evident in only 11 out of 35 families, and other patients were apparently sporadic. The rate of penetrance was very low. Symptomatic siblings of familial cases showed a late age of onset, male preponderance and clinical features similar to those of the probands. Asymptomatic carriers, predominantly female, were detected relatively late in life. The geographical distribution of these late-onset, FAP TTR Met30 cases was scattered throughout Japan. In three autopsy cases and 20 sural nerve biopsy specimens, neurons in sympathetic and sensory ganglia were relatively preserved. Amyloid deposition was seen in the peripheral nervous system, particularly in the sympathetic ganglia, dorsal root ganglia and proximal nerve trunks such as sciatic nerve. These abnormalities were milder than those seen in typical early-onset FAP TTR Met30, as observed in two Japanese endemic foci of this disease. While axonal degeneration was prominent in myelinated fibres, resulting in severe fibre loss, unmyelinated fibres were relatively preserved. Our cases of late-onset FAP TTR Met30 showed features distinct from those of typical early-onset FAP TTR Met30 that occurred in the two Japanese endemic foci. Factors responsible for clinicopathological differences between these two forms of FAP TTR Met30 need to be identified.

To analyze the peripheral nerve pathological abnormalities in familial amyloid polyneuropathy, a correlative pathological study was carried out on the spinal nerve roots, proximal sciatic nerves, sural nerves, and brachial plexuses from 3 patients with the disease in Japan. The spinal nerve roots appeared to be unaffected except for amyloid deposition on the epineurium. In sciatic nerves and brachial plexuses the nerve lesions had a multifocal distribution, showing prominent interstitial edema in the endoneurium frequently adjacent to deposits of amyloid; in these regions the nerve fibers were severely depleted. A teased-fiber study revealed that segmental demyelination was the predominant type of nerve fiber abnormality. However, these findings were not seen in the sural nerves; instead a diffuse fiber loss with axonal degeneration was observed. It is suggested that multifocal lesions in the proximal portions of the long extremity nerves could summate distally to produce a symmetrical polyneuropathy in the disease. In addition to a space-occupying effect of amyloid deposits in the endoneurium, severe endoneurial edema associated with amyloid deposition in blood vessels and the endoneurial interstitium may induce ischemia in nerve fibers, thus causing the progressive polyneuropathy in this disorder.

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BackgroundPrediabetes is an independent risk factor for cardiovascular diseases. Mean platelet volume (MPV) can reflect platelet activity, and high MPV is associated with thrombogenic activation and an increased risk of cardiovascular disease. In diabetic patients, MPV is higher when compared with normal subjects. However, the relationship between MPV and prediabetes is poorly understood. The purpose of the present study was to compare MPV in prediabetic and normoglycemic subjects, and to evaluate the relationship between MPV and fasting plasma glucose (FPG) levels in these two groups.MethodsWe retrospectively studied 1876 Japanese subjects who had undergone health checks at Iida Municipal Hospital. Age, sex, body mass index (BMI), blood pressure, medical history, smoking habits, alcohol intake, lipid profiles, FPG levels, and MPV were evaluated. Subjects were categorized into four groups according to FPG: Q1 (70 mg/dL ≤ FPG < 90 mg/dL, n = 467), Q2 (90 mg/dL ≤ FPG < 95 mg/dl, n = 457), Q3 (95 mg/dL ≤ FPG < 100 mg/dL, n = 442), and Q4 (100 mg/dL ≤ FPG < 126 mg/dL, n = 512). Q1, Q2, and Q3 were defined as normal FPG groups and Q4 was defined as prediabetic group.ResultsThe MPV increased with the increasing FPG levels, in the following order: Q1 (9.89 ± 0.68 fl), Q2 (9.97 ± 0.69 fl), Q3 (10.02 ± 0.72 fl), and Q4 (10.12 ± 0.69 fl). After adjusting for the confounding parameters, MPV of the prediabetic group was higher than that in other groups (P < 0.001 for Q4 vs. Q1 and Q2, and P < 0.05 for Q4 vs. Q3). MPV in the high-normal glucose group (Q3) was significantly higher than in the low-normal glucose group (Q1). MPV was independently and positively associated with FPG, not only in prediabetic subjects but also in normal FPG subjects (β = 0.020 and β = 0.006, respectively).ConclusionsMPV in patients with prediabetes was higher than that in normal subjects, and was positively associated with FPG levels in prediabetic and normal subjects.

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