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.

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.

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.

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.

Clinicopathological features of adult-onset neuronal intranuclear inclusion disease.

Neuronal intranuclear inclusion disease (NIID) is a slowly progressive neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions in the central and peripheral nervous system, and also in the visceral organs. NIID has been considered to be a heterogeneous disease because of the highly variable clinical manifestations, and ante-mortem diagnosis has been difficult. However, since we reported the usefulness of skin biopsy for the diagnosis of NIID, the number of NIID diagnoses has increased, in particular adult-onset NIID. In this study, we studied 57 cases of adult-onset NIID and described their clinical and pathological features. We analysed both NIID cases diagnosed by post-mortem dissection and by ante-mortem skin biopsy based on the presence of characteristic eosinophilic, hyaline and ubiquitin-positive intanuclear inclusion: 38 sporadic cases and 19 familial cases, from six families. In the sporadic NIID cases with onset age from 51 to 76, dementia was the most prominent initial symptom (94.7%) as designated 'dementia dominant group', followed by miosis, ataxia and unconsciousness. Muscle weakness and sensory disturbance were also observed. It was observed that, in familial NIID cases with onset age less than 40 years, muscle weakness was seen most frequently (100%), as designated 'limb weakness group', followed by sensory disturbance, miosis, bladder dysfunction, and dementia. In familial cases with more than 40 years of onset age, dementia was most prominent (100%). Elevated cerebrospinal fluid protein and abnormal nerve conduction were frequently observed in both sporadic and familial NIID cases. Head magnetic resonance imaging showed high intensity signal in corticomedullary junction in diffusion-weighted image in both sporadic and familial NIID cases, a strong clue to the diagnosis. All of the dementia dominant cases presented with this type of leukoencephalopathy on head magnetic resonance imaging. Both sporadic and familial NIID cases presented with a decline in Mini-Mental State Examination and Frontal Assessment Battery scores. Based on these clinicopathological features, we proposed a diagnosis flow chart of adult-onset NIID. Our study suggested that the prevalence rate of adult-onset NIID may be higher than previously thought, and that NIID may be underdiagnosed. We should take NIID into account for differential diagnosis of leukoencephalopathy and neuropathy.

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.

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.

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 unclassifiable sporadic four-repeat tauopathy presenting with parkinsonism and speech disturbances.

A 48-year-old Japanese woman experienced slow-onset parkinsonism and speech disturbances. Neurological examinations revealed rigidity in the trunk and extremities, bradykinesia and postural instability, although cognitive impairments and psychiatric symptoms were not apparent in the early disease stage. Neuroimaging revealed progressive bilateral frontotemporal lobe atrophy with cerebral blood flow hypoperfusion. No apparent signs of lower motor neuron involvement were observed, such as fasciculation or electromyogram findings. She eventually reached the akinetic mutism state, and gastrostomy and tracheotomy were performed at 4 years after onset. A clinical diagnosis of progressive supranuclear palsy was made prior to her death, which occurred 6 years after onset. Post mortem examinations revealed that the brain weighed 1200 g and showed atrophy of the frontotemporal lobe and brainstem. Severe neuron loss and gliosis were observed in the frontotemporal lobe. The superior and middle frontal gyri were the most severely affected and showed spongiform changes in the superficial layer. The globus pallidus, subthalamic nucleus, cerebellar dentate nucleus, substantia nigra and inferior olivary nucleus also showed neuronal loss with gliosis. Using hyperphosphorylated tau (AT-8) immunostaining, pretangle-like neurons, numerous short threads and glial tau pathology were extensively observed. Using Gallyas-Braak silver staining, thin and short threads were also extensively observed, but considerably fewer than those observed by AT-8 immunostaining. Neither astrocytic plaques nor tuft-shaped astrocytes were observed. Examination by immunoelectron microscopy showed straight fibrils approximately 15 nm in diameter in the neuronal cytoplasmic inclusions in the cerebral cortex and in the fibrillary structures in the cerebral white matter. Western blot analysis of sarkosyl-insoluble tau revealed predominantly four-repeat tau and a banding pattern similar to that seen in progressive supranuclear palsy. No pathogenic mutations were found during the gene analysis of microtubule-associated protein tau. After completing our comprehensive investigation, we diagnosed this patient with unclassifiable four-repeat tauopathy.

Diffuse large B-cell lymphoma recurring with zosteriform cutaneous lesions.

A 75-year-old woman presented with edema of the left leg in December 2012. On examination, there was a palpable 5-cm tumor in the left lower abdomen, and PET/CT showed lymphadenopathy of the tracheal, para-aortic, left iliac and inguinal regions with increased FDG uptake. We performed histopathological examination of the iliac lymph node and diagnosed diffuse large B-cell lymphoma (DLBCL), stage IIIA. The patient received 8 courses of R-CHOP chemotherapy and achieved a complete response. In April 2014, she noticed seven new painful erythematous vesicles <1 cm in size on the skin of the left lower abdominal region. Herpes zoster was suspected and valacyclovir was administered. However, this medication had no effect, and the vesicles enlarged and became nodular. Histopathological examination of one of the skin lesions revealed the infiltration of DLBCL and the diagnosis of zosteriform cutaneous recurrence of DLBCL was thus made. Skin lesions mimicking herpes zoster have been reported in certain types of hematological malignancies, and histopathological diagnosis should be performed in such cases.

An autopsied case of adult-onset bulbospinalform Alexander disease with a novel S393R mutation in the GFAP gene.

A 50-year-old Japanese man with no apparent family history noticed diplopia. He gradually showed gait disturbance and dysuria. Abducens disorder of eye movement with nystagmus, tongue atrophy with fasciculation, spastic tetraparesis, and sensory disturbance were also observed. MRI showed severe atrophy of the medulla oblongata to the cervical cord ("tadpole appearance"). Tracheotomy and gastrostomy were performed 7 years after onset due to the development of bulbar palsy. Death occurred following respiratory failure after 11 years total disease duration. The brain weighed 1,380 g. The cerebrum, cerebellum, midbrain, and upper pons were preserved from atrophy, but the medulla oblongata to the cervical cord showed severe atrophy. A few Rosenthal fibers were observed in the cerebral white matter, basal ganglia, and cerebellum, whereas numerous Rosenthal fibers were observed in the medulla oblongata to the cervical cord. Myelin loss with relatively preserved axons was extensively observed from the middle of the pons to the spinal cord. The clinicopathological diagnosis was adult-onset bulbospinal-form Alexander disease. Glial fibrillary acidic protein (GFAP) gene analysis revealed a novel mutation of S393R. Expression patterns of S393R mutant GFAP using adrenal carcinoma-derived cells (SW13 cells) showed a decreased number of filamentous structures and abnormal aggregates.

Presenile onset of spinocerebellar ataxia type 1 presenting with conspicuous psychiatric symptoms and widespread anti-expanded polyglutamine antibody- and fused in sarcoma antibody-immunopositive pathology.

A 50-year-old Japanese man showed slowly progressive gait disturbance and dysarthria. Neurological examination 5 years after onset revealed slow eye movement with nystagmus as well as limb and truncal ataxia. Magnetic resonance imaging showed atrophy of the cerebellum and brainstem. Because genetic examination revealed CAG repeat expansion of the ataxin-1 gene, the patient was diagnosed with spinocerebellar ataxia type 1. Ten years after onset, he showed psychiatric symptoms with cognitive impairment, and antipsychotic drugs were administered. As psychiatric symptoms gradually worsened, particularly with regard to resisting nursing care and shouting, the doses of the drugs were increased. Although the clinicopathologic findings were generally identical to previously reported spinocerebellar ataxia type 1 cases with the exception of the conspicuous psychiatric symptoms, there are two notable immunohistochemical findings. Firstly, numerous anti-expanded polyglutamine antibody-immunopositive neuronal inclusions were extensively observed, including in the cerebral cortex and limbic system, but not in the Purkinje cells. Secondly, anti-fused in sarcoma antibody-immunopositive intranuclear inclusions were extensively observed. We posit that the anti-expanded polyglutamine antibody-immunopositive neuronal inclusions and possibly the anti-fused in sarcoma antibody-immunopositive inclusions, particularly those in the neocortex and limbic system, may correspond to the psychiatric symptoms and cognitive impairment that were observed in the patient.

Latex-enhanced turbidimetric immunoassay for everolimus in whole blood using the Nanopia TDM everolimus assay with the JCA-BM6010 automatic analyzer.

BACKGROUND: Everolimus is a novel proliferation signal inhibitor used in immunosuppressive therapies for the prevention of acute and chronic rejection. It is an immunosuppressant requiring routine monitoring in whole blood. We evaluated analytical performance of the Nanopia TDM Everolimus assay kit for the measurement of everolimus in whole blood. METHODS: Whole blood samples from patients receiving immunosuppressive therapy with everolimus after heart transplantation were used, and everolimus concentrations were measured by liquid chromatography combined with mass spectrometric detection and fluorescence polarization immunoassay and Nanopia TDM Everolimus assay. RESULTS: The within-assay coefficient of variation was 4.0%-6.8% (n = 20) at everolimus concentrations of 4.4-15.7 ng/mL, whereas the day-to-day coefficient of variation ranged from 3.6% to 5.4% at everolimus concentrations of 4.8-15.9 ng/mL. The limit of quantitation was 1.5 ng/mL. Calibration curves were stable for at least 14 days. The presence of conjugated bilirubin, unconjugated bilirubin, lipemic material, rheumatoid factor, and variation of the hematocrit did not affect this assay system. There was a strong positive correlation between values obtained with the Nanopia TDM Everolimus assay kit and the results of liquid chromatography combined with mass spectrometric detection (y = 0.960x + 0.312 ng/mL; r = 0.946; n = 91), as well as with data from the fluorescence polarization immunoassay (y = 0.966x - 0.440 ng/mL; r = 0.942; n = 91). CONCLUSIONS: The Nanopia TDM Everolimus assay showed good analytical performance. These results indicate that the Nanopia TDM Everolimus assay may be suitable for routine clinical use.

Gerstmann-Straeussler-Scheinker disease with P102L prion protein gene mutation presenting with rapidly progressive clinical course.

We describe an autopsied case of a Japanese woman with Gerstmann-Straeussler-Scheinker disease (GSS) presenting with a rapidly progressive clinical course. Disease onset occurred at the age of 54 with dementia and gait disturbance. Her clinical course progressively deteriorated until she reached a bedridden state with myoclonus 9 months after onset. Two months later, she reached the akinetic mutism state. Nasal tube feeding was introduced at this point and continued for several years. Electroencephalograms showed diffuse slowing without periodic sharp-wave complexes. Diffusion-weighted magnetic resonance imaging (MRI) showed widespread cerebral cortical hyperintensity. Prion protein (PrP) gene analysis revealed a Pro to Leu point mutation at codon 102 with methionine homozygosity at codon 129. The patient died of respiratory failure after a total disease duration of 62 months. Neuropathologic examination revealed widespread spongiform change with numerous eosinophilic amyloid plaques (Kuru plaques) in the cerebral and cerebellar cortices by H & E staining. Diffuse myelin pallor with axon loss of the cerebral white matter, suggestive of panencephalopathic-type pathology was observed. Numerous PrP immunopositive plaques and diffuse synaptic-type PrP deposition were extensively observed, particularly in the cerebral and cerebellar cortices. Western blot analysis of proteinase Kresistant PrP showed a characteristic band pattern with a small molecular band of 6 kDa. The reason for the similarity in clinicopathologic findings between the present case and Creutzfeldt-Jakob disease is uncertain; however, the existence of an unknown disease-modifying factor is suspected.

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.

An autopsied case of progressive supranuclear palsy presenting with cerebellar ataxia and severe cerebellar involvement.

A Japanese male patient presented with gait disturbance at the age of 69 years. His principal symptom was cerebellar ataxia for several years. He was initially diagnosed as having olivopontocerebellar atrophy because dysarthria and ataxia gradually developed, and head CT scan showed apparent atrophy of the cerebellum and brainstem and dilatation of the fourth ventricle. Later, he showed vertical gaze palsy, dysphagia, retrocollis, parkinsonism, axial dominant rigidity and grasp reflex, and therefore, the diagnosis was modified to progressive supranuclear palsy (PSP). Progressive atrophy of the frontotemporal lobe, cerebellum and brainstem, and dilatation of the lateral, third and fourth ventricles were evident on MRI. Gastrostomy and tracheotomy were performed 9 and 10 years after onset, respectively, and the patient died after 11 years disease duration. At autopsy the brain weighed 1000 g and showed atrophy of the frontotemporal lobe, cerebellum and brainstem. Neurofibrillary tangles, mainly globose-type revealed by Gallyas-Braak silver staining, were extensively observed in the cerebral cortex and subcortical grey matter. Numerous glial fibrillary tangles, including tuft-shaped astrocytes and coiled bodies, and extensive argyrophilic threads were also recognized, particularly in the frontal lobe, basal ganglia, cerebellar white matter, brainstem and spinal cord. The Purkinje cell layer showed severe neuron loss with Bergmann's gliosis, and the dentate nucleus showed severe neuron loss with grumose degeneration. Tau-positive/Gallyas-positive inclusions in the Purkinje cells and the glial cells of the Purkinje cell layer were observed. Pathological findings of the present patient were consistent with the diagnosis of PSP, but the olivopontocerebellar involvement, particularly in the cerebellum, was generally more severe, and the quantity of tau-positive/Gallyas-positive structures were more abundant than in typical PSP cases. The existence of a distinct, rare PSP subtype with severe olivopontocerebellar involvement, "PSP-C", which tends to be clinically misdiagnosed as spinocerebellar degeneration in the early disease stage, is noteworthy. The present case corresponded to this rare subtype of PSP.

Senile onset frontotemporal lobar degeneration with TAR-DNA binding protein 43 proteinopathy primarily presenting with wasteful habits.

We present an autopsied case of a senile Japanese woman with sporadic frontotemporal lobar degeneration (FTLD) presenting as frontotemporal dementia. Disease onset was at the age of 70 and presented as a behaviour disorder, particularly involving wasteful habits. The patient had repeated incidents of making expensive purchases and then had difficulty making payments. Following these symptoms, she showed other changes of character such as lethargy and apathy. She gradually showed signs of parkinsonism including rigidity and bradykinesia, and in the terminal stage, an akinetic mutism state with quadriplegia in flexion was observed. Head magnetic resonance imaging revealed severe frontotemporal lobe atrophy with severe lateral ventricular dilatation and frontal white matter degeneration. At autopsy, the brain weighed 930 g and the frontotemporal cerebral cortex showed neuron loss with gliosis, tissue rarefaction and spongiform change, particularly in the superficial layers. Pathologic degeneration was more severe in the anterior portion of the frontal lobe with extensive white matter degeneration. Immunostaining for phosphorylated TAR-DNA binding protein 43 (TDP-43) revealed numerous neuronal cytoplasmic inclusions and extensive short dystrophic neuritis, particularly in the frontotemporal cortex. Many TDP-43-positive cytoplasmic inclusions were also observed in the dentate gyrus of the hippocampus. The patient was pathologically diagnosed with FTLD with TDP-43-positive inclusions (FTLD-TDP) without motor neuron disease. The immunohistochemical findings corresponded to type A of the FTLD-TDP pathology classification system.