Bilateral Prefrontal Cortex Blood Flow Dynamics during Silent and Oral Reading Using Near-Infrared Spectroscopy.

This study aimed to investigate blood flow dynamics in the bilateral prefrontal cortex during silent and oral reading using near-infrared spectroscopy (NIRS). The subjects were 40 right-handed university students (20.5±1.8 years old, 20 men and 20 women). After completing the NIRS measurements, the subjects were asked to rate their level of proficiency in silent and oral reading, using a 5-point Likert scale. During oral reading, the left lateral prefrontal cortex (Broca's area) was significantly more active than the right side. During silent reading, prefrontal cortex activity was lower than that during oral reading, and there was no significant difference between both sides of the brain. A significant negative correlation was found between the change in oxy-hemoglobin (oxy-Hb) concentration in the left and right lateral prefrontal cortex during silent reading and silent reading speed. In addition, students with lower self-reported reading proficiency had significantly greater changes in oxy-Hb concentrations in the left and right lateral prefrontal cortex during silent/oral reading than did students with higher self-reported reading proficiency. Reading task assessment using NIRS may be useful for identifying language lateralization and Broca's area. The results demonstrate that NIRS is useful for assessing effortful reading and may be used to diagnose developmental dyslexia in children. J. Med. Invest. 71 : 92-101, February, 2024.

Clinical course of pathologically confirmed corticobasal degeneration and corticobasal syndrome.

The clinical presentation of corticobasal degeneration is diverse, while the background pathology of corticobasal syndrome is also heterogeneous. Therefore, predicting the pathological background of corticobasal syndrome is extremely difficult. Herein, we investigated the clinical findings and course in patients with pathologically, genetically and biochemically verified corticobasal degeneration and corticobasal syndrome with background pathology to determine findings suggestive of background disorder. Thirty-two patients were identified as having corticobasal degeneration. The median intervals from the initial symptoms to the onset of key milestones were as follows: gait disturbance, 0.0 year; behavioural changes, 1.0 year; falls, 2.0 years; cognitive impairment, 2.0 years; speech impairment, 2.5 years; supranuclear gaze palsy, 3.0 years; urinary incontinence, 3.0 years; and dysphagia, 5.0 years. The median survival time was 7.0 years; 50% of corticobasal degeneration was diagnosed as corticobasal degeneration/corticobasal syndrome at the final presentation. Background pathologies of corticobasal syndrome (n = 48) included corticobasal degeneration (33.3%), progressive supranuclear palsy (29.2%) and Alzheimer's disease (12.5%). The common course of corticobasal syndrome was initial gait disturbance and early fall. In addition, corticobasal degeneration-corticobasal syndrome manifested behavioural change (2.5 years) and cognitive impairment (3.0 years), as the patient with progressive supranuclear palsy-corticobasal syndrome developed speech impairment (1.0 years) and supranuclear gaze palsy (6.0 years). The Alzheimer's disease-corticobasal syndrome patients showed cognitive impairment (1.0 years). The frequency of frozen gait at onset was higher in the corticobasal degeneration-corticobasal syndrome group than in the progressive supranuclear palsy-corticobasal syndrome group [P = 0.005, odds ratio (95% confidence interval): 31.67 (1.46-685.34)]. Dysarthria at presentation was higher in progressive supranuclear palsy-corticobasal syndrome than in corticobasal degeneration-corticobasal syndrome [P = 0.047, 6.75 (1.16-39.20)]. Pyramidal sign at presentation and personality change during the entire course were higher in Alzheimer's disease-corticobasal syndrome than in progressive supranuclear palsy-corticobasal syndrome [P = 0.011, 27.44 (1.25-601.61), and P = 0.013, 40.00 (1.98-807.14), respectively]. In corticobasal syndrome, decision tree analysis revealed that 'freezing at onset' or 'no dysarthria at presentation and age at onset under 66 years in the case without freezing at onset' predicted corticobasal degeneration pathology with a sensitivity of 81.3% and specificity of 84.4%. 'Dysarthria at presentation and age at onset over 61 years' suggested progressive supranuclear palsy pathology, and 'pyramidal sign at presentation and personality change during the entire course' implied Alzheimer's disease pathology. In conclusion, frozen gait at onset, dysarthria, personality change and pyramidal signs may be useful clinical signs for predicting background pathologies in corticobasal syndrome.

Multiple system atrophy variant with severe hippocampal pathology.

The striatonigral and olivopontocerebellar systems are known to be vulnerable in multiple system atrophy (MSA), showing neuronal loss, astrogliosis, and alpha-synuclein-immunoreactive inclusions. MSA patients who displayed abundant neuronal cytoplasmic inclusions (NCIs) in the regions other than the striatonigral or olivopontocerebellar system have occasionally been diagnosed with variants of MSA. In this study, we report clinical and pathologic findings of MSA patients characterized by prominent pathologic involvement of the hippocampus. We assessed 146 consecutively autopsied MSA patients. Semi-quantitative analysis of anti-alpha-synuclein immunohistochemistry revealed that 12 of 146 patients (8.2%) had severe NCIs in two or more of the following areas: the hippocampal granule cells, cornu ammonis areas, parahippocampal gyrus, and amygdala. In contrast, the remaining 134 patients did not show severe NCIs in any of these regions. Patients with severe hippocampal involvement showed a higher representation of women (nine women/three men; Fisher's exact test, p = 0.0324), longer disease duration (13.1 ± 5.9 years; Mann-Whitney U-test, p = 0.000157), higher prevalence of cognitive impairment (four patients; Fisher's exact test, p = 0.0222), and lower brain weight (1070.3 ± 168.6 g; Mann-Whitney U-test, p = 0.00911) than other patients. The hippocampal granule cells and cornu ammonis area 1/subiculum almost always showed severe NCIs. The NCIs appeared to be ring-shaped or neurofibrillary tangle-like, fibrous configurations. Three of 12 patients also had dense, round-shaped NCIs that were morphologically similar to pick bodies. The patients with Pick body-like inclusions showed more severe atrophy of the medial temporal lobes and broader spreading of NCIs than those without. Immunohistochemistry for hyperphosphorylated tau and phosphorylated TDP-43 revealed minimal aggregations in the hippocampus of the hippocampal MSA patients. Our observations suggest a pathological variant of MSA that is characterized by severe involvement of hippocampal neurons. This phenotype may reinforce the importance of neuronal alpha-synucleinopathy in the pathogenesis of MSA.

Usefulness of wearable fitness tracking devices in patients undergoing esophagectomy.

BACKGROUND: Esophageal cancer surgery requires maintenance and enhancement of perioperative nutritional status and physical function to prevent postoperative complications. Therefore, awareness of the importance of preoperative patient support is increasing. This study examined the usefulness of using a diary in combination with a wearable fitness tracking device (WFT) in patients undergoing surgery for esophageal cancer. METHODS: Ninety-four patients who underwent esophagectomy between February 2019 and April 2021 were included. Physicians, nurses, dietitians, and physical therapists provided diary-based education for the patients. In addition, a WFT was used by some patients. The perioperative outcomes of patients who used both the diary and WFT (WFT group) and those who used the diary alone (non-WFT group) were compared. In addition, propensity score matching was performed to improve comparability between the two groups. RESULTS: After the propensity score matching, the rate of postoperative pneumonia was significantly lower in the WFT group (0% vs. 22.6%, P = 0.005). The postoperative hospital stay was shorter in the WFT group (P = 0.012). Nutritional status indices, such as the prognostic nutritional index, also improved significantly in the WFT group at 1 month after surgery (P = 0.034). The rate of diary entries was significantly higher in the WFT group (72.3% vs. 28.3%, P < 0.001). CONCLUSION: The use of a WFT reduced the incidence of postoperative pneumonia and improved postoperative nutritional status and rates of diary entries after esophagectomy, suggesting that its use may be useful for promoting recovery after esophagectomy.

Usefulness of Near-Infrared Spectroscopy (NIRS) for evaluating drug effects and improvements in medication adherence in children with Attention Deficit Hyperactivity Disorder (ADHD).

The symptoms of attention deficit hyperactivity disorder (ADHD) are inattention, hyperactivity, and impulsiveness. Physicians often prescribe methylphenidate (MPH) for children with ADHD for long periods of time. The purpose of the present study was to investigate the usefulness of near-infrared spectroscopy (NIRS) for evaluating drug effects and improvements in medication adherence in children with ADHD. Subjects were 10 male children diagnosed with ADHD : average age, 9.3 years, and 10 boys with typical development : average age 9.5 years. Children with intellectual disability, autism, and obvious depressive symptoms were excluded. The present study revealed that in the ADHD group, oxy-Hb concentrations in the left and right lateral prefrontal cortex significantly increased during the execution of the Stroop color-word test in both channels when taking MPH. This method was considered to be useful for assessing drug effects on ADHD because NIRS is an objective indicator for evaluating ADHD executive dysfunction and visualizes the activation of frontal lobe function by MPH. A pediatric neurologist explained the results of NIRS while presenting images to the ADHD group, and medication adherence and the drug-taking ratio both markedly improved. Therefore, this therapeutic explanation is an effective strategy for improving medication compliance and adherence among patients. J. Med. Invest. 68 : 53--58, February, 2021.

System degeneration in an MM1-type sporadic Creutzfeldt-Jakob disease case with an unusually prolonged akinetic mutism state.

Methionine/methionine type 1 (MM1-type) sporadic Creutzfeldt-Jakob disease (sCJD), known as the 'classic type,' shows typical clinicopathological sCJD findings. In general, patients reach an akinetic mutism state within a few months of disease onset and die soon after if supportive therapies are not administered. Here, we describe remarkable neuropathologic observations of MM1-type sCJD in a 48-year-old, Japanese man with an unusually prolonged akinetic mutism state. In the early disease stages, the patient exhibited abnormal behaviour with gait disturbance and rapidly progressive cognitive dysfunction. Diffusion-weighted magnetic resonance imaging revealed extensive cerebral cortical hyperintensity. Prion protein (PrP) gene analysis revealed no mutations, and the polymorphic codon 129 exhibited methionine homozygosity. Although the patient remained stable with tube feeding for more than 2 years after reaching the akinetic mutism state, he died because of central respiratory failure 30 months after disease onset. Neuropathologic investigation showed extensive devastating lesions, such as status spongiosus, and typical spongiform changes could no longer be observed in the cerebral neocortex. Conspicuous pyramidal tract degeneration was observed. However, the regions commonly preserved in MM1-type sCJD pathology were still relatively preserved. Immunostaining revealed extensive diffuse synaptic-type PrP deposition in the grey matter. The pathological findings suggested that sCJD is a neurodegenerative disease that shows system degeneration; there are primary and secondary degenerative regions and distinct preserved regions, even in cases with prolonged disease duration. In addition, it is considered that there is a limited survival period for MM1-type sCJD, even if active symptomatic treatment is provided.

Aberrant interaction between FUS and SFPQ in neurons in a wide range of FTLD spectrum diseases.

Fused in sarcoma (FUS) is genetically and clinicopathologically linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). We have previously reported that intranuclear interactions of FUS and splicing factor, proline- and glutamine-rich (SFPQ) contribute to neuronal homeostasis. Disruption of the FUS-SFPQ interaction leads to an increase in the ratio of 4-repeat tau (4R-tau)/3-repeat tau (3R-tau), which manifests in FTLD-like phenotypes in mice. Here, we examined FUS-SFPQ interactions in 142 autopsied individuals with FUS-related ALS/FTLD (ALS/FTLD-FUS), TDP-43-related ALS/FTLD (ALS/FTLD-TDP), progressive supranuclear palsy, corticobasal degeneration, Alzheimer's disease, or Pick's disease as well as controls. Immunofluorescent imaging showed impaired intranuclear co-localization of FUS and SFPQ in neurons of ALS/FTLD-FUS, ALS/FTLD-TDP, progressive supranuclear palsy and corticobasal degeneration cases, but not in Alzheimer's disease or Pick's disease cases. Immunoprecipitation analyses of FUS and SFPQ revealed reduced interactions between the two proteins in ALS/FTLD-TDP and progressive supranuclear palsy cases, but not in those with Alzheimer disease. Furthermore, the ratio of 4R/3R-tau was elevated in cases with ALS/FTLD-TDP and progressive supranuclear palsy, but was largely unaffected in cases with Alzheimer disease. We concluded that impaired interactions between intranuclear FUS and SFPQ and the subsequent increase in the ratio of 4R/3R-tau constitute a common pathogenesis pathway in FTLD spectrum diseases.

A case of V180I genetic Creutzfeldt-Jakob disease presenting with conspicuous facial mimicry.

Although there have been no reports of facial mimicry in patients with Creutzfeldt-Jakob disease (CJD), we encountered a patient with genetic CJD with prion protein gene codon 180 mutation (V180I gCJD) who apparently showed this interesting clinical finding. The patient was an 87-year-old Japanese woman, and the first observed CJD symptom was poor spontaneity. She gradually showed cognitive dysfunction and subsequently gait disturbance. A prion protein gene analysis revealed a V180I mutation with methionine homozygosity at codon 129. Facial mimicry was observed 7 months after disease onset and continued for approximately 9 months. Pathological laughing and startle reaction were also observed during approximately the same period, whereas myoclonus was observed at a later stage, 12 months after disease onset, and was very mild in degree. Electroencephalography studies showed a diffuse slow basic pattern without periodic sharp wave complexes. Diffusion-weighted magnetic resonance imaging showed extensive hyperintensity in the cerebral cortex, and there was also hyperintensity with edematous swelling in the same regions on T2-weighted and fluid-attenuated inversion recovery images. On the basis of the magnetic resonance imaging findings and the findings of previous case reports of V180I gCJD, we speculate that the characteristic extensive cerebrocortical involvement observed in V180I gCJD was implicated in the pathogenesis of the facial mimicry observed in this case.

Long-read sequencing identifies GGC repeat expansions in NOTCH2NLC associated with neuronal intranuclear inclusion disease.

Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disease that is characterized by eosinophilic hyaline intranuclear inclusions in neuronal and somatic cells. The wide range of clinical manifestations in NIID makes ante-mortem diagnosis difficult1-8, but skin biopsy enables its ante-mortem diagnosis9-12. The average onset age is 59.7 years among approximately 140 NIID cases consisting of mostly sporadic and several familial cases. By linkage mapping of a large NIID family with several affected members (Family 1), we identified a 58.1 Mb linked region at 1p22.1-q21.3 with a maximum logarithm of the odds score of 4.21. By long-read sequencing, we identified a GGC repeat expansion in the 5' region of NOTCH2NLC (Notch 2 N-terminal like C) in all affected family members. Furthermore, we found similar expansions in 8 unrelated families with NIID and 40 sporadic NIID cases. We observed abnormal anti-sense transcripts in fibroblasts specifically from patients but not unaffected individuals. This work shows that repeat expansion in human-specific NOTCH2NLC, a gene that evolved by segmental duplication, causes a human disease.

Autopsied centenarian case of Alzheimer's disease combined with hippocampal sclerosis, TDP-43, and α-synuclein pathologies.

A Japanese woman showed slowly progressive memory disturbance starting at the age of 84 years, and disorientation gradually appeared. Head computed tomography revealed severe hippocampal atrophy, whereas the atrophy of the frontal lobe was considerably mild for her age. Behavioral and psychological symptoms of dementia were relatively inconspicuous during the disease course. Apolipoprotein E gene analysis showed ε3/ε4 heterozygosity. She died at the age of 100 years and she was clinically diagnosed as having Alzheimer's disease (AD). Autopsy revealed numerous neurofibrillary tangles, particularly in the hippocampal region, and extensively distributed senile plaques in the brain. Although the findings were compatible with the pathological criteria for AD, combined pathologies of hippocampal sclerosis, trans-activation response DNA-binding protein 43 kDa, and α-synuclein were also revealed. We believe that the clinicopathological findings of the present case are of significance for the diagnosis of elderly dementia and pathogenesis of AD.

Pathological diagnosis of combined Alzheimer's disease and argyrophilic grain dementia in a very elderly man who presented with advanced behavioural and psychological symptoms.

This case report describes a Japanese man who presented with slowly progressive memory disturbances that began at the age of 79 years. The man also displayed conspicuous behaviour and psychological symptoms in the early stage of dementia. Computed tomography revealed atrophy of the amygdala and severe hippocampal deterioration, particularly in the anterior portion. Lateral ventricular dilatation, mainly affecting the anterior and inferior horns, was also observed. Interestingly, cerebral neocortical atrophy in the frontal and temporal lobes was considerably mild for the patient's age. Apolipoprotein E gene analysis showed epsilon 3 homozygosity. The patient died at the age of 96 years, and his clinical diagnosis was Alzheimer's disease with severe behavioural and psychological symptoms of dementia. In addition to indicating considerable hippocampal atrophy, an autopsy revealed numerous neurofibrillary tangles and argyrophilic grains in the brain, as well as extensive senile plaques. Cerebral amyloid angiopathy was also recognized. The pathological findings were suggestive of both Alzheimer's disease and argyrophilic grain dementia; other neurodegenerative disorders were not apparent. The clinicopathologic findings of the present case suggest significant consideration should be made when determining the clinical diagnosis and pathogenesis of senile dementia.

Posterior Vitreous Detachment as Observed by Wide-Angle OCT Imaging.

PURPOSE: Posterior vitreous detachment (PVD) plays an important role in vitreoretinal interface disorders. Historically, observations of PVD using OCT have been limited to the macular region. The purpose of this study is to image the wide-angle vitreoretinal interface after PVD in normal subjects using montaged OCT images. DESIGN: An observational cross-sectional study. PARTICIPANTS: A total of 144 healthy eyes of 98 normal subjects aged 21 to 95 years (51.4±22.0 [mean ± standard deviation]). METHODS: Montaged images of horizontal and vertical OCT scans through the fovea were obtained in each subject. MAIN OUTCOME MEASURES: Montaged OCT images. RESULTS: By using wide-angle OCT, we imaged the vitreoretinal interface from the macula to the periphery. PVD was classified into 5 stages: stage 0, no PVD (2 eyes, both aged 21 years); stage 1, peripheral PVD limited to paramacular to peripheral zones (88 eyes, mean age 38.9±16.2 years, mean ± standard deviation); stage 2, perifoveal PVD extending to the periphery (12 eyes, mean age 67.9±8.4 years); stage 3, peripapillary PVD with persistent vitreopapillary adhesion alone (7 eyes, mean age 70.9±11.9 years); stage 4, complete PVD (35 eyes, mean age 75.1±10.1 years). All stage 1 PVDs (100%) were observed in the paramacular to peripheral region where the vitreous gel adheres directly to the cortical vitreous and retinal surface. After progression to stage 2 PVD, the area of PVD extends posteriorly to the perifovea and anteriorly to the periphery. Vitreoschisis was observed in 41.2% at PVD initiation (stage 1a). CONCLUSIONS: Whereas prior work suggests that PVD originates in the perifoveal region and after the sixth decade, our observations demonstrate that (1) PVD first appears even in the third decade of life and gradually appears more extensively throughout life; (2) more than 40% of eyes without fundus diseases at their PVD initiation are associated with vitreoschisis; and (3) PVD is first noted primarily in the paramacular-peripheral region where vitreous gel adheres to the retinal surface and is noted to be more extensive in older ages to ultimately involve the fovea.

Longitudinal clinical and neuro-radiological findings in a patient with leukoencephalopathy with brain calcifications and cysts (Labrune syndrome).

Since she was 4 years old, the patient had exhibited frequent convulsive seizures, and she experienced severe headaches and depression in adulthood. At the age of 37 years, cerebral calcifications were detected, but she exhibited no cognitive or motor problems. She suffered a cerebral haemorrhage at 49 years old and experienced cognitive dysfunction, dysarthria, dysphagia, and left-hemiparesis as sequelae. After undergoing gastrostomy, she exhibited very slow cognitive deterioration associated with speech disturbance over more than 10 years. She also gradually developed limb spasticity with Babinski signs. Repeated computerised tomography scans revealed unexpected changes including 2 cysts that appeared separately after small haemorrhages, an intracerebral haemorrhage, and intra-cyst bleeding. These longitudinal scans also showed progressive ventricular dilatation and expansion of the leukoencephalopathy, but there were no apparent changes in the intracranial calcifications. Magnetic resonance imaging revealed numerous microbleeds, and magnetic resonance angiography revealed irregularity of the cerebral artery walls with stoppage. Her SNORD118 gene exhibited compound heteromutation of c.38C > G and c.116G > C on different alleles. She was finally diagnosed with leukoencephalopathy with brain calcifications and cysts (Labrune syndrome) at the age of 61 years. Past reports have suggested that diffuse cerebral microangiopathy underlies Labrune syndrome's pathogenesis, but we speculate that cerebral macroangiopathy may also underlie it.

An autopsied case of corticobasal degeneration presenting with frontotemporal dementia followed by myoclonus.

A Japanese woman developed frontotemporal dementia (FTD)-like symptoms of abnormal behavior, such as stereotyped behavior and disinhibition. The patient developed these symptoms at the age of 59 years, although aphasia symptoms were not apparent at early disease stages. Progressive parkinsonism was dominant on the left side, and conspicuous myoclonus was recognized in the late disease stage. MRI indicated severe, right side-dominant frontotemporal lobe atrophy with white matter degeneration. Brainstem and cerebellar atrophy were also observed. The patient underwent gastrostomy 7 years after the onset of her symptoms and died at the age of 70 years. Neuropathological examination showed diffuse neuron loss with gliosis and tissue rarefaction in the frontotemporal lobe, particularly in the right anterior portion of the frontal lobe. Spongiform changes and ballooned neurons were also observed in the frontotemporal cortex, particularly in the superficial layer and deeper layers, respectively. Gallyas-Braak silver staining and anti-phosphorylated tau immunostaining indicated numerous argyrophilic and tau-positive structures, including pretangles, astrocytic plaques, coiled bodies and neuropil threads. We speculate that the myoclonus observed in the present case was at least partly caused by or related to the spongiform change and ballooned neurons in the cerebral cortex. The clinical phenotypes of corticobasal degeneration (CBD) vary considerably, and the clinical presentation of the present patient was compatible with frontal behavioral-spatial syndrome in the early disease stage. However, in the later disease stages, her symptoms were reflective of corticobasal syndrome. Because it is not rare for the clinical phenotype to change along with disease progression in cases of CBD, we should consider CBD in cases presenting with FTD at symptom onset.

An autopsy case of Creutzfeldt-Jakob disease with a prion protein gene codon 180 mutation presenting with pathological laughing and an exaggerated startle reaction.

A 78-year-old Japanese woman presented with slow progressive disorientation and memory disturbances. Pathological laughing was observed at an early disease stage and continued for several months. Around the same time, the patient began to exhibit an exaggerated startle reaction and mild myoclonus. The pathological laughing and startle reaction disappeared before the patient reached an akinetic mutism state approximately 16 months after symptom onset. MRI showed extensive hyperintensity of the cerebral cortex and striatum on diffusion-weighted images, and swelling in the cerebral cortex on T2-weighted and fluid attenuated inversion recovery images. A prion protein (PrP) gene analysis revealed a V180I mutation with methionine homozygosity at codon 129. Neuropathological examination showed extensive spongiform changes with characteristic various-sized and non-confluent (VaSNoC) vacuoles in the cerebral neocortex and striatum. Gliosis and hypertrophic astrocytosis were generally mild in character. Neurons were relatively preserved in number. We believe that pathological laughing and an exaggerated startle reaction are possible pathognomonic findings of V180I genetic Creutzfeldt-Jakob disease. Based on the pathological findings of the present case, the presence of the VaSNoC-type spongiform changes with relative preservation of the neurons in the cerebral cortex and a lack of apparent brainstem involvement are associated at least in part with the pathological laughing and startle reaction.

Gastrostomy in patients with prion disease.

Patients with prion diseases can live for long periods of time in a state of akinetic mutism given appropriate management of their symptoms. To study symptom support in these cases, we performed gastrostomies on 3 patients with V180I genetic Creutzfeldt-Jakob disease (CJD) who had become akinetic and mute, and compared them to 14 other similar patients being fed by tube. In the 3 gastrostomy cases, there were no direct complications due to the gastrostomy or tube feeding, nor were there episodes of discontinuation of tube feeding or initiation of continuous drip infusion due to severe complications. Antibiotics were administered for mild infections, a complication of CJD, with 0.2% and 8.8% of the total time after gastrostomy being used for intravenous or transluminal administration, respectively. We compared the present patient series with that of our previous report statistically, and found that patients undergoing gastrostomy required significantly fewer discontinuations of tube feeding than those who did not. No significant difference in antibiotic administration was found between groups, however. It is our conclusion that gastrostomy should be allowed for symptom support in akinetic patients with prion disease, but adequate informed consent must be provided to the patient's family.

Hematopoietic neoplasms accompanied by severe enterocolitis due to Aeromonas species.

Aeromonas species are known to be a cause of diarrhea and acute enterocolitis. However, only a few cases have been reported and the pathophysiology of Aeromonas infection has not as yet been clarified. We experienced 2 cases developing severe enterocolitis during the course of hematological malignancies, specifically multiple myeloma and diffuse large B-cell lymphoma. Both patients presented with watery diarrhea that persisted for more than a week, followed by bloody diarrhea. Total colon endoscopy showed multiple ulcers on the mucosa from the sigmoid colon to the rectum, and biopsies from the ulcer revealed infiltration of neutrophils and eosinophils in the mucosa and submucosa. Aeromonas hydrophila and Aeromonas sobria were isolated from stool cultures, respectively. Treatment with oral ciprofloxacin was effective in both patients and clinical symptoms showed significant improvement. These cases raise the possibility of Aeromonas infection as a cause of severe enterocolitis and the importance of making a correct differential diagnosis and appropriate antibiotic treatment in immunocompromised patients including those with hematological malignancies.

An autopsied case of MM1 + MM2-cortical with thalamic-type sporadic Creutzfeldt-Jakob disease presenting with hyperintensities on diffusion-weighted MRI before clinical onset.

A 78-year-old Japanese man presented with rapidly progressive dementia and gait disturbances. Eight months before the onset of clinical symptoms, diffusion-weighted magnetic resonance imaging (DWI) demonstrated hyperintensities in the right temporal, right parietal and left medial occipital cortices. Two weeks after symptom onset, DWI showed extensive hyperintensity in the bilateral cerebral cortex, with regions of higher brightness that existed prior to symptom onset still present. Four weeks after clinical onset, periodic sharp wave complexes were identified on an electroencephalogram. Myoclonus was observed 8 weeks after clinical onset. The patient reached an akinetic mutism state and died 5 months after onset. Neuropathological examination showed widespread cerebral neocortical involvement of fine vacuole-type spongiform changes with large confluent vacuole-type spongiform changes. Spongiform degeneration with neuron loss and hypertrophic astrocytosis was also observed in the striatum and medial thalamus. The inferior olivary nucleus showed severe neuron loss with hypertrophic astrocytosis. Prion protein (PrP) immunostaining showed widespread synaptic-type PrP deposition with perivacuolar-type PrP deposition in the cerebral neocortex. Mild to moderate PrP deposition was also observed extensively in the basal ganglia, thalamus, cerebellum and brainstem, but it was not apparent in the inferior olivary nucleus. PrP gene analysis showed no mutations, and polymorphic codon 129 showed methionine homozygosity. Western blot analysis of protease-resistant PrP showed both type 1 scrapie type PrP (PrPSc ) and type 2 PrPSc . Based on the relationship between the neuroimaging and pathological findings, we speculated that cerebral cortical lesions with large confluent vacuoles and type 2 PrPSc would show higher brightness and continuous hyperintensity on DWI than those with fine vacuoles and type 1 PrPSc . We believe the present patient had a combined form of MM1 + MM2-cortical with thalamic-type sporadic Creutzfeldt-Jakob disease (sCJD), which suggests a broader spectrum of sCJD clinicopathological findings.

An autopsy case of a centenarian with the pathology of senile dementia of the neurofibrillary tangle type.

A Japanese woman showed slowly progressive memory disturbance since the age of 85 years. Later, disorientation gradually appeared. Head computed tomography revealed severe hippocampal atrophy, particularly in the posterior portion, and lateral ventricular dilatation, particularly in the inferior horn at the age of 99 years. The amygdala was relatively preserved from atrophy, and atrophy of the frontal lobe was relatively mild for her age. Apolipoprotein E gene analysis showed the ε3 homozygous phenotype. The woman died at the age of 101 years, and her clinical diagnosis was mild Alzheimer's disease. No apparent behavioural and psychological symptoms of dementia were observed during the disease course. Autopsy revealed severe hippocampal atrophy with numerous neurofibrillary tangles and ghost tangles, particularly in the hippocampal region, but senile plaques were rarely observed in the brain. The pathological findings were compatible with senile dementia of the neurofibrillary tangle type, whereas other neurodegenerative disorders were not recognized. The clinicopathologic findings of the present case are considered significant for the clinical diagnosis and pathogenesis of senile dementia of the neurofibrillary tangle type.