[A case of methotrexate-associated diffuse large B-cell lymphoma with splenial lesions of the corpus callosum on brain MRI after complete remission with chemotherapy].

An 86-year-old woman in a wheelchair was accompanied by her husband and son as she visited our outpatient clinic due to disturbed consciousness and fever. Twenty-seven years earlier, she had been diagnosed with rheumatoid arthritis and had been treated with methotrexate (MTX) and low-dose prednisolone (PSL). She stopped taking MTX four years previously when she was diagnosed with diffuse large B cell lymphoma of the paranasal sinus. Her lymphoma went into remission after six cycles of systemic immunochemotherapy. MRI after hospitalization revealed a lesion in the splenium of the corpus callosum that was hyperintense on diffusion-weighted imaging and which had low apparent diffusion coefficient values. An analysis of the cerebrospinal fluid revealed no atypical cells. The MRI findings were atypical, but her consciousness disturbance improved, leading to the diagnosis of mild encephalitis/encephalopathy with a reversible splenial lesion, which would be associated with a transient consciousness disturbance with a good course. However, her consciousness worsened over the next 3 weeks. One month later, a contrast-enhanced MRI showed an enlarged lesion in the callosum as well as new lesions, and the diagnosis of secondary CNS lymphoma was made. Brain biopsy is often not feasible. Less invasive and highly accurate diagnostic methods are needed, such as the identification of a spinal fluid tumor marker.

Efficacy of a high dosage of donepezil for Alzheimer's disease as examined by single-photon emission computed tomography imaging.

BACKGROUND: The efficacy of donepezil 10 mg/day against Alzheimer's disease (AD) was examined, with a primary focus on changes in cerebral blood flow (CBF) as determined by single-photon emission computed tomography imaging. METHODS: The subjects were 24 outpatients who had been diagnosed with probable AD, which had progressed to advanced AD. Mini-Mental State Examination and Alzheimer's Disease Assessment Scale (ADAS) scores were determined before and after the donepezil dosage increase. (99m) Tc-ethylcysteinate dimer single-photon emission computed tomography was performed to evaluate changes in CBF. Then, a comparative study evaluated changes after the donepezil dosage increased. RESULTS: After the donepezil dosage increase, adverse effects associated with gastrointestinal symptoms were observed in one patient, and irritability was observed in three. The average Mini-Mental State Examination score changed from 15.25 ± 6.24 to 14.67 ± 6.07; significant changes were not observed. Seventeen subjects were evaluated with the Alzheimer's Disease Assessment Scale-cognitive subscale. After the dosage increase, the average subscale score decreased from 24.52 ± 13.39 to 21.56 ± 9.14, and significant improvement was observed (P = 0.021). With respect to changes in the CBF, the values of all three indicators decreased after the higher dosage increased CBF. However, no significant differences were observed in CBF. Analysis performed after the donepezil dosage increase revealed significant increases in CBF in the right occipital and temporal lobes, left temporal lobe, right parietal lobe, and both parts of the posterior cerebellum. CONCLUSION: Increasing the donepezil dosage from 5 mg/day to 10 mg/day is effective for the treatment of AD.

[The efficacy and adverse effects of rituximab with CHOP or THP-COP in old-old and extremely old patients with diffuse large B cell lymphoma].

AIM: We examined the efficacy and adverse effects of rituximab with CHOP (cyclophosphamide, doxorubicin, vincristin, prednisone) or THP-COP (pirarubicin, cyclophosphamide, vincristin, prednisone) in previously untreated old-old and extremely old patients with diffuse large B cell lymphoma (DLBCL). METHODS: Subjects were 13 initial DLBCL patients consisting of 7 men and 8 women with a median age of 79 years (range 75-91 years). These patients received CHOP or THP-COP plus 375mg/m2 rituximab intravenously given on the day before each cycle. The dose was adjusted depending on the patient's age and associated complications. Administration was performed for 6 to 8 cycles, whenever possible. RESULTS: Seven patients (54%) achieved a complete response (CR), 4 (31%) achieved a partial response (PR), 2 (15%) failed to respond. The 2-year survival rates were 62%. The CR rate and survival rate were higher than in patients previously treated with CHOP alone in our hospital, but there was no statistically significant difference. The most frequent adverse effect was bone marrow suppression, observed in 9 patients (69.2%). Adverse effects that seemed to be infusion reaction occurred in 4 patients (30.7%). These adverse effects related to infusion reaction disappeared by reducing or stopping rituximab. Four (30.7%) patients died and 3 of those died due to disease progression. One of those died 1.5 month after he began chemotherapy and the cause of death was unknown. CONCLUSION: This result suggested that both CHOP and THP-COP combined with rituximab were safe and effective for old-old and extremely old patients.

Rate of progression of Alzheimer's disease in younger versus older patients: a longitudinal single photon emission computed tomography study.

AIM: Although several researchers have examined the effect of age on disease progression in patients with Alzheimer's disease (AD), the results are controversial. We investigated the effect of age on the rate of progression of cognitive impairment and on regional cerebral blood flow (rCBF) deficits using longitudinal single photon emission computed tomography (SPECT) studies. METHODS: We divided 75 patients with AD who were followed up for 24-90 months into the younger AD group (n=32, age at initial examination ≤ 75 years) and the older AD group (n=43, age at initial examination >75 years). We assessed changes in Mini-Mental State Examination (MMSE) scores and rCBF between initial and final examinations. RESULTS: The change in the annual MMSE score was greater in the younger AD group than in the older AD group. The mean annual MMSE score changes correlated significantly with age at the initial examination. The initial and follow-up SPECT studies showed more severe and extensive rCBF deficits in the younger AD group than in the older AD group. CONCLUSION: Our longitudinal SPECT study showed that the rate of progression of cognitive impairment and the rCBF deficits were higher in younger patients with AD than in older patients with AD. Therefore, age is an important factor to consider, not only in the diagnosis, but also in the treatment and prognosis of patients with AD.

Clinical results and issues of acute myeloid leukemia in elderly patients aged 75 years and older.

AIM: Clinical outcomes of acute myeloid leukemia (AML) in elderly patients still remain unsatisfactory and the optimal treatment has yet to be clearly established. This report describes the results of a retrospective study of clinical outcomes and prognostic factors of AML in patients aged 75 years and older. In addition, we aimed to elucidate the situation of patients with AML accompanied by dementia, which has been largely ignored in previous studies. METHODS: The subjects consisted of 31 patients with untreated AML (including previous myelodysplastic syndrome: AML/MDS). All patients underwent chemotherapy, with 25 undergoing conventional therapy and six undergoing low-intensity therapy. RESULTS: Complete remission was obtained in 16 of the 31 cases (51.6%), with a 3-year survival rate of 11.5%. However, in seven cases, Alzheimer's disease (AD) was observed. Although we were able to perform induction therapy in each of these cases, consolidation therapy was difficult in cases of moderate AD. CONCLUSION: The results of this study suggest that even very elderly patients can benefit from chemotherapy. However, it is thought that the treatment selection for cases which are complicated by moderate to severe dementia should be determined carefully while considering the patient's quality of life.

Changes in cognitive functions of patients with dementia of the Alzheimer type following long-term administration of donepezil hydrochloride: relating to changes attributable to differences in apolipoprotein E phenotype.

AIM: We conducted a study of changes in cognitive functions by long-term monitoring of dementia of Alzheimer type (DAT) patients to investigate the relationship between the progression of DAT symptoms and the presence of apolipoprotein (ApoE)4. METHODS: The subjects consisted of 40 DAT patients who had been treated with donepezil for 3 years or more. The Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale - Cognitive Subscale Japanese version (ADAS-Jcog), were conducted annually. The patients were categorized into ApoE4(+) and ApoE4(-) groups. Changes in initial cognitive function assessment score (0 years) were then studied longitudinally at each stage of the observation period (1, 2, 3 years) (Wilcoxon's signed-rank test). Moreover, the scores at each time period were compared cross-sectionally between the two groups (Mann-Whitney U-test). RESULTS: Significant decreases in MMSE scores were observed at the three time periods in both groups (P < 0.01) in the cross-sectional study. In the longitudinal study, the ApoE4(+) group demonstrated a lower trend (P < 0.1) after 1 year only. Significantly poorer ADAS-Jcog scores were observed in the ApoE4(+) group at the 3-year point both in the longitudinal and in the cross-sectional study (P < 0.05). For ADAS-Jcog sub-items, in the longitudinal study, orientation was demonstrated to be significantly poorer in the ApoE4(+) group in the third year (P < 0.05). CONCLUSION: ApoE4 was suggested to not only be a risk factor for disease onset, but also a risk factor for exacerbation of symptoms with respect to long-term prognosis.