Global cognition and executive functions of older adults with type 1 diabetes mellitus without dementia.

AIMS/INTRODUCTION: This study aimed to characterize the global cognition and executive functions of older adults with type 1 diabetes mellitus in comparison with type 2 diabetes mellitus. MATERIALS AND METHODS: This study included 37 patients with type 1 diabetes mellitus aged ≥65 years and 37 age- and sex-matched patients with type 2 diabetes mellitus. Patients with dementia scoring <24 on the Mini-Mental State Examination were excluded. General cognition, memory, classic, and practical executive function were investigated. RESULTS: Patients with type 1 diabetes mellitus demonstrated lower psychomotor speed scores on Trail Making Tests A and B (P < 0.001, P < 0.013) than those with type 2 diabetes mellitus. The dysexecutive syndrome behavioral assessment revealed similar results in patients with types 1 and 2 diabetes mellitus. The Wechsler Memory Scale-Revised verbal episodic memory and Montreal Cognitive Assessment Japanese version were similar in terms of general cognition, but worse delayed recall subset on the latter was associated with type 2 diabetes mellitus (P = 0.038). A worse Trail Making Test-A performance was associated with type 1 diabetes mellitus and age (P < 0.004, P < 0.029). CONCLUSIONS: Executive function of psychomotor speed was worse in older outpatient adults without dementia with type 1 diabetes mellitus than in those with type 2 diabetes mellitus but with no significant differences in the comprehensive and practical behavioral assessment of dysexecutive syndrome. Patients with type 1 diabetes had more severely impaired executive function, whereas those with type 2 had greater impaired memory than executive function.

Odor identification score as an alternative method for early identification of amyloidogenesis in Alzheimer's disease.

A simple screening test to identify the early stages of Alzheimer's disease (AD) is urgently needed. We investigated whether odor identification impairment can be used to differentiate between stages of the A/T/N classification (amyloid,  tau, neurodegeneration) in individuals with amnestic mild cognitive impairment or AD and in healthy controls. We collected data from 132 Japanese participants visiting the Toranomon Hospital dementia outpatient clinic. The odor identification scores correlated significantly with major neuropsychological scores, regardless of apolipoprotein E4 status, and with effective cerebrospinal fluid (CSF) biomarkers [amyloid ß 42 (Aß42) and the Aß42/40 and phosphorylated Tau (p-Tau)/Aß42 ratios] but not with ineffective biomarkers [Aß40 and the p-Tau/total Tau ratio]. A weak positive correlation was observed between the corrected odor identification score (adjusted for age, sex, ApoE4 and MMSE), CSF Aß42, and the Aß42/40 ratio. The odor identification score demonstrated excellent discriminative power for the amyloidogenesis stage , according to the A/T/N classification, but was unsuitable for differentiating between the p-Tau accumulation and the neurodegeneration stages. After twelve odor species were analyzed, a version of the score comprising only four odors-India ink, wood, curry, and sweaty socks-proved highly effective in identifying AD amyloidogenesis, showing promise for the screening of preclinical AD.

Extracellular vesicle proteome unveils cathepsin B connection to Alzheimer's disease pathogenesis.

Extracellular vesicles (EVs) are membrane vesicles that are released extracellularly and considered to be implicated in the pathogenesis of neurodegenerative diseases including Alzheimer's disease. Here, CSF EVs of 16 ATN-classified cases were subjected to quantitative proteome analysis. In these CSF EVs, levels of 11 proteins were significantly altered during the ATN stage transitions (P < 0.05 and fold-change > 2.0). These proteins were thought to be associated with Alzheimer's disease pathogenesis and represent candidate biomarkers for pathogenic stage classification. Enzyme-linked immunosorbent assay analysis of CSF and plasma EVs revealed altered levels of cathepsin B (CatB) during the ATN transition (seven ATN groups in validation set, n = 136). The CSF and plasma EV CatB levels showed a negative correlation with CSF amyloid-ß42 concentrations. This proteomic landscape of CSF EVs in ATN classifications can depict the molecular framework of Alzheimer's disease progression, and CatB may be considered a promising candidate biomarker and therapeutic target in Alzheimer's disease amyloid pathology.

[Brentuximab vedotin and cord blood transplantation for primary refractory Hodgkin lymphoma following autologous hematopoietic stem cell transplantation].

We report a 26-year-old man with primary refractory nodular sclerosis Hodgkin lymphoma against ABVD, ICE and autologous peripheral blood stem cell transplantation (auto-PBSCT), presenting with multiple epidural spinal cord compressions, paraplegia, and generalized lymphadenopathy. We administrated four cycles of brentuximab vedotin to achieve a complete response, and then conducted cord blood transplantation. This case raises the possibility of a new strategy for refractory Hodgkin lymphoma showing residual lesions after auto-PBSCT.

Psychogenic unilateral ptosis with ipsilateral muscle spasm of orbicular oculi.

This report describes the rare case of a 27-year-old female patient with conversion disorder who presented unilateral ptosis with ipsilateral muscle spasm of orbicular oculi. The co-existing of ptosis and muscle spasm of orbicular oculi indicates that, in accord with prior reports, the overactivity of orbicular oculi is essential in psychogenic pseudoptosis. The co-existing of unilateral ptosis and ipsilateral muscle spasm of orbicular oculi in the present case leads us to the conclusion that the overactivity of orbicular oculi is essential in psychogenic pseudoptosis.

Secondary hypertrophic pachymeningitis in antiphospholipid syndrome.

This report describes a rare case of hypertrophic pachymeningitis secondary to antiphospholipid syndrome in a 37-year-old woman. The patient had a history of antiphospholipid syndrome and developed hypertrophic pachymeningitis subsequently. Pathological examination of the dura mater showed not only fibrous thickening, the typical finding of hypertrophic pachymeningitis, but also thrombosis in the dural microvessels and T cell infiltration without B cell or plasma cell infiltration, suggesting cell-mediated immunity. The dural thickening spontaneously improved and did not deteriorate during corticosteroid therapy. The histological findings and spontaneous remission observed in this case might be characteristic of secondary hypertrophic pachymeningitis with antiphospholipid syndrome. Further investigations are necessary to elucidate the pathophysiology of this novel type of hypertrophic pachymeningitis.

Steroid-responsive focal epilepsy with focal dystonia accompanied by glutamate receptor delta2 antibody.

This report describes a rare case presenting with focal epilepsy and focal dystonia associated with glutamate receptor δ2 antibody. The patient was a 47-year-old male patient with neurosyphilis. He presented with an intractable focal seizure spreading from the right arm, with dystonia of the left leg. The IgG antibody of glutamate receptor δ2 was detected. Ictal and interictal SPECT suggested focal epilepsy in the left frontal cortex. Antibiotic and antiepileptic drugs were ineffective, although steroid pulse therapy effectively diminished the patient's symptoms. Inflammatory mechanisms may have contributed to this disorder.

Rectal ulcer in a patient with VZV sacral meningoradiculitis (Elsberg syndrome).

This report describes the case of a 55-year-old woman with varicella-zoster virus (VZV) sacral meningoradiculitis (Elsberg syndrome) who presented with herpes zoster in the left S2 dermatome area, urinary retention, and constipation. Lumbar magnetic resonance imaging showed the left sacral nerve root swelling with enhancement. Thereafter, she suddenly showed massive hematochezia and hemorrhagic shock because of a rectal ulcer. To elucidate the relation between Elsberg syndrome and rectal ulcer, accumulation of similar cases is necessary. To avoid severe complications, attention must be devoted to the possibility of rectal bleeding in the early stage of Elsberg syndrome.

Recurrent spinal cord attacks in a patient with a limited form of neuromyelitis optica.

This report describes the case of a 71-year-old woman with a limited form of neuromyelitis optica (NMO) who had a longitudinally extensive spinal cord lesion from the fourth to the tenth thoracic vertebrae. Up to age 75, she had four subsequent recurrences of the myelitis within the same spinal cord area but with no optic neuritis. Anti-AQP4 antibody was seropositive. Recurrence within the same spinal cord area might be a characteristic clinical finding in NMO spectrum disorders. For such patients, examination for anti-AQP4 antibody might be necessary for the diagnosis and therapy of this disorder.

A novel ferritin light chain gene mutation in a Japanese family with neuroferritinopathy: description of clinical features and implications for genotype-phenotype correlations.

Neuroferritinopathy is a hereditary neurodegenerative disorder caused by mutations in the ferritin light chain gene (FTL1). The cardinal features are progressive movement disturbance, hypoferritinemia, and iron deposition in the brain. To date, five mutations have been described in Caucasian and Japanese families, but the genotype-phenotype correlations remain to be established. We identified a novel FTL1 mutation (exon 4, c.641/642, 4-nucletotide duplication) in a Japanese family and compared the clinical traits with those previously reported. All mutations but one are insertions in exon 4, resulting in frameshifts. Clinical features are similar among patients with the same mutations. Middle-age onset chorea is common in patients with insertions in the 5' portion of exon 4 including our cases, whereas patients with insertions in the 3' portion of exon 4 develop early-onset tremor, suggesting genotype-phenotype correlations. In this family, male predominance and normal serum ferritin levels are characteristic.

Massive myelinolytic leukoencephalopathy in a patient medicated with low-dose oral methotrexate for rheumatoid arthritis: an autopsy report.

The authors describe a 68-year-old female who developed a rapidly progressing leukoencephalopathy involving the cerebrum and brain stem. The disease appeared during low-dose oral methotrexate (MTX) therapy for rheumatoid arthritis. An extensive clinical investigation discounted other possible causes of white matter lesions. Autopsy identified an uninterrupted severe demyelinating, partially liquefactive necrosis-like lesion in the white matter accompanied by astrogliosis and occasional swollen axons therein. The lesion was generally symmetrical, and distributed throughout the whole cerebral white matter except for the bilateral temporal lobes and the rostral part of the frontal lobes. The internal capsules and cerebral peduncles were spongy, and the central and lateral parts of the pons, especially the transverse cerebellopontine tracts, were affected similarly. It was of note that the lesion was accompanied by neither vascular diseases nor lymphocyte infiltration. Thus, the pathological findings were similar to those of a severe form of central and extrapontine myelinolysis, and clearly different from ordinary MTX leukoencephalopathy reported in patients receiving intrathecal or intravenous MTX therapy, known as "disseminated necrotizing leukoencephalopathy". Another possibility is that synergistic effects of several white-matter-damaging disorders may have contributed to the hitherto unknown lesion. To our knowledge, this is the first autopsy record that describes an oral MTX-associated neurological disorder.

[An adult case of bacterial meningitis caused by penicillin-resistant streptococcus pneumoniae].

We report a patient of bacterial meningitis caused by penicillin-resistant streptococcus pneumoniae (PRSP). A 50-year-old Japanese man was admitted after developing a fever and quickly falling into unconsciousness. Neurological examination showed slightly consciousness disturbance and meningeal irritation. A lumbar puncture yielded turbid spinal fluid, with increased cell count (411/mm3), protein (685 mg/dl) and IgG (60.3 mg/dl) but decreased glucose (1 mg/dl). Bacterial meningitis was diagnosed and aminobenzylpenicillin (ABPC) and cefotaxime (CTX) were administered immediately, but they were ineffective. Penicillin-resistant streptcoccus pneumoniae (PRSP) was detected in the blood and spinal fluid, so antibiotics were changed to panipenem/betamipron (PAPM/BP) and vancomycin (VCM) with marked efficacy. With the increase in PRSP patients and documented failure in treatment of pneumococcal meningitis with ABPC and CTX, the need for alternative antibiotic therapy is critical. We emphasize the importance of initial therapy with PAPM/BP and VCM in patients with bacterial meningitis from streptcoccus pneumoniae.