Severe cerebrovascular pathology of the first supercentenarian to be autopsied in the world.

We report on a 116-year-old Japanese woman who was the first officially documented supercentenarian to be autopsied in the world. She lived a remarkably healthy life until suffering cerebral infarction at 109 years of age. She became Japan's oldest person at 113 years and died in 1995 from colon cancer at 116 years 175 days. Her medical records show the delayed onset of stroke, cancer, dementia, and heart disease and the importance of appropriate medical treatment and intensive dedicated care provided during the last stage of her life. She was the longest-lived person in Japan for 21 years from 1993 until 2014. The neuropathological findings of her autopsied brain were briefly reported in the Japanese literature in 1997. In this study, we reinvestigated her brain and spinal cord in more detail. Severe cerebrovascular lesions and cervical spondylotic myelopathy were found to be the main causes of her disability. Although the density of senile plaques was relatively high, the distribution of neurofibrillary tangles was limited. Ghost tangles and argyrophilic grains were mild. The mildness of tau pathological changes in her neurons, in other words the resistance of neurons to tau pathology, may be a factor responsible for her longevity.

Acute motor and sensory neuronopathy associated with small-cell lung cancer: a clinicopathological study.

A 48-year-old Chinese woman developed ascending motor paralysis while visiting Japan, leading to tetraplegia and respiratory failure over 2 weeks. The patient's course was complicated by anoxic encephalopathy. Nerve conduction studies revealed a severely decreased amplitude of compound muscle action potentials and a sural nerve biopsy specimen showed findings consistent with axonal-form Guillain-Barr6 syndrome. An autopsy, excluding the brain, demonstrated small-cell lung cancer that was not detected clinically, axonal-dominant degeneration in the nerve roots and distal peripheral nerves, and the loss of both myelin and axons in the dorsal spinal column. The spinal anterior horn cells were severely decreased and were accompanied by astrocytic reaction in all spinal segments with lymphocytic infiltration. A limited examination of the dorsal root ganglia did not show Nageotte nodules, but the infiltration of T cells was observed. Although the clinical course mimicked axonal-form Guillain-Barré syndrome, the autopsy demonstrated both sensory and motor neuronal involvement, as well as small-cell lung cancer. Although anti-Hu and antiganglioside antibodies were negative in the patient's serum, the para-neoplastic mechanism might have damaged the anterior horn and dorsal root ganglia cells, which subsequently led to secondary axonal degeneration. There has been a report on a case of paraneoplastic subacute motor neuronopathy, but the acute course described here has not been reported before.

Secondary hemophagocytic syndrome in a patient with methicillin-sensitive Staphylococcus Aureus bacteremia due to severe decubitus ulcer.

A 51-year-old man with poliomyelitis was admitted to emergency because of a severe decubitus ulcer on his right hip that was associated with infection. His general condition deteriorated and he was malnourished and dehydrated. Despite adequate hyperalimentation and antibiotic administration, laboratory data indicated pancytopenia 4 days later. He was diagnosed as having secondary hemophagocytosis (HPS) associated with methicillin-sensitive Staphylococcus aureus sepsis due to decubitus inflammation based on bone marrow aspiration and a blood culture. Although granulocyte colony stimulating factor, packed red blood cell transfusions, platelet transfusions, and antibiotics gradually improved the pancytopenia, the patient died of massive gastrointestinal tract bleeding.

[CD5- CD11c+ CD23- small lymphocytic lymphoma evolving from aplastic anemia].

A 91-year-old woman was hospitalized with acute respiratory distress syndrome due to pneumonia in June 1997. Since she had pancytopenia and a bone marrow aspirate indicated hypocellularity with no increase in myeloblasts, dysplasia or abnormal chromosomes, aplastic anemia (AA) was diagnosed. Pulse therapy with methylprednisolone and antibiotics proved successful, and blood cell numbers stabilized. In June 2001, she was readmitted to our hospital with persistent low grade fever and leukopenia. A bone marrow aspirate from the sternum and iliac bone biopsy revealed compact proliferation of small lymphocytes, and the surface marker CD5- CD10- CD11c+ CD19+ CD20+ CD23- was detected through immune staining and flowcytometry. CD30+, CD34+and CD56+cells were scarce. Tests for surface immunoglobulins, IgG, IgA, IgM and IgD, were negative. No nodal or extranodal lesions were evident. Since Southern blot analysis of bone marrow cells indicated rearrangement of the immunoglobulin heavy chain and abnormal chromosomes were evident, small lymphocytic lymphoma (SLL) was diagnosed. Four intravenous infusions of rituximab (375mg/m2) were administered without critical adverse effects. Tests conducted four weeks later revealed saturation of CD20+ antigens of lymphoma cells and chromosomal abnormalities and rearrangement of the immunoglobulin heavy chain were still apparent. Though complete remission of the pancytopenia was not achieved, serum concentrations of lactate dehydrogenase and soluble interleukin-2 receptor decreased, and the numbers of platelets and erythrocytes increased. There was also an improvement in systemic condition. This was a rare case of SLL having the surface marker of CD5- CD10- CD11c+ CD19+ CD20+ CD23-, which had evolved from AA and infiltrated bone marrow.

Histopathological investigation of salivary glands in the asymptomatic elderly.

The significance of labial gland biopsies (LGBs) in the diagnosis of Sjögren's syndrome (SS) in the elderly has been a controversial subject since it is complicated by age-related histopathological changes. In an attempt to clarify the appropriateness of LGBs in present diagnosis criteria, we evaluated the specificity of LGBs using autopsied tissues. This was done by taking labial, sublingual and submandibular salivary glands from 53 autopsy subjects (24 males and 29 females) with an average age of 84 years, and testing them histopathologically with reference to a previously reported grading system. None had any sicca symptoms (oral dryness or dry eye). In subjects up to 75 years old, acinar atrophy was more frequent in labial glands than in the two major salivary glands (P=0.0098 for sublingual and P=0.0009 for submandibular glands). Also, while there were significant differences in frequency of such atrophy between the sublingual and submandibular salivary glands of subjects younger and older than 75, the labial glands showed no such variation. Taking grade 3 (focus score of 1) as the diagnosis criterion, two subjects were determined to have SS in which case the specificity was 95%. Using contemporaneous serological test results for anti-SSA/Ro antibodies as a diagnostic criterion raised specificity to 98%. For both major and minor glands, these appeared to be no relationship between degree of lymphocytic infiltration and age. Our results thus suggest that it is appropriate to adopt a focus score of 1 as a diagnostic criterion for SS in the elderly, and that serological test results can improve specificity.

[Clinical significance of soluble interleukin-2 receptor as a putative systemic nutritional index in the elderly].

The clinical significance of a slight increase of serum soluble interleukin-2 receptor (sIL2R) concentration in the stable elderly was investigated. Thirty-five residents of nursing homes with physical impairment as a sequel to cerebral infarctions, without any inflammatory condition, anodyne or immunological treatment, were divided into two groups: 24 without overt or suspected malignancy (NC) and 11 with a history of malignancy (CA). Serological screening with measurement of sIL2 R concentrations was performed and numbers of lymphocytes with CD4, CD8 markers were determined. The NC group was divided into controls (n = 15, sIL2R < = 883 U/mL) and subjects demonstrating elevation (n = 9, NH), as in a previous study. Differences were found in serum concentrations of albumin, blood urea nitrogen, total cholesterol concentration, Pettigrew's prognostic nutritional index (PNI), as well as the ADL score, but not age or sex between NH and controls. Factor analysis in NC revealed serum creatinine and blood urea nitrogen concentrations to correlate positively, and serum albumin, total cholesterol concentrations, ADL score, PNI to correlate negatively to sIL2R. Differences were found in sIL2R, albumin, total protein, total cholesterol, beta-lipoprotein, PNI between CA and controls, but correlations were not found in CA. Survival rate of controls over twenty-four months was better than that of NH, but not of CA. Our results suggest that a slight increase of concentration of sIL2R is related to subclinical systemic deterioration, especially with regard to nutrition, with a plausible connection to prognosis of the stable elderly without malignancy.

[A case of multiple myeloma with infiltration into skeletal muscle after injections of a granulocyte-colony stimulating-factor].

Multiple myelomas often occur in elderly people with complications due to aging. A 54-year-old man was first admitted with cerebral infarction, and multiple myeloma (IgG kappa, stage IIIA) occurred in November 1989 that was followed by partial remission after chemotherapy. The karyotype of the bone marrow cells was 46, XY, and no p53 gene mutations were detected by polymerase chain reaction and single-strand conformation polymorphism analysis. Chemotherapy (melphalan 10 mg, vindesine 3 mg, ranimustine 150 mg, prednisolone 60 mg for 4 days) was performed in February 1999 because of aggravation of the myeloma. After daily subcutaneous injection of 50 micrograms of nartograstim for six days to treat neutropenia, soft tissues around the right eye were swelled gradually without redness, accompanied by elevation of the serum creatine-kinase concentration. The swelling disappeared, and the enzyme level normalized after discontinuation of nartograstim. In July, on the sixth day of daily subcutaneous injection of 75 micrograms of filgrastim after the same chemotherapy, similar swelling of the soft tissues around the left eye became evident, and again this proved reversible. In July 2000, 40 mg of dexamethasone was infused, and after 5-day subcutaneous-injection of 75 micrograms of filgrastim daily, the right subclavicular soft tissue became swollen. He died of myocardial infarction, and autopsy revealed infiltration of myeloma cells into the right subclavicular muscle and bone marrow packed with myeloma cells. This case suggests that myeloma cells can proliferate and infiltrate into soft tissues on exposure to granulocyte-colony stimulating factors.