Ryota Kobayashi

Few studies have longitudinally evaluated Hashimoto's encephalopathy with anti-NH2-terminal α-enolase (anti-NAE) antibodies using detailed imaging and neuropsychological assessments. We present the case of a man in his 50s who presented with acute hallucinations, catatonia, seizures, and cognitive decline. Initial MRI revealed diffuse white matter hyperintensities, and SPECT revealed widespread hypoperfusion. These symptoms improved with immunotherapy, but progressive frontal and temporal atrophy and residual hypoperfusion appeared over 33 months. His cognitive function improved, but he remained impaired, with persistent disinhibition and perseveration. This case suggests that Hashimoto's encephalopathy with anti-NAE antibodies can cause lasting structural and functional brain abnormalities and cognitive impairments, requiring long-term neuroimaging and neuropsychological follow-up.

Frontotemporal lobar degeneration (FTLD) encompasses frontotemporal dementia and related neurological disorders including motor neuron disease and movement disorders. During the 21th century, analyses of aggregative proteins suggested powerful hypotheses of gain-of-neurotoxicity or loss-of-function for aggregation-related proteins. However, recent translational researches in collaboration of basic studies and human pathology indicate that FTLD arises from more complex molecular mechanisms than dyshomeostasis of single molecules. Additionally, accumulation of clinicopathological evidences from various countries, genetic backgrounds or clinical specialties (e.g. neurology and psychiatry), suggests diverse phenotypes of FTLD, which are indicative of future paradigm-shift in the concept of FTLD. In this paper, we discuss FTLD pathomechanism on the basis of human pathology.

Variants in VCP (encoding valosin-containing protein) lead to inclusion body myopathy, which is typically associated with Paget's disease of the bones and frontotemporal dementia (FTD). When symptoms of frontotemporal lobar degeneration (FTLD) develop in patients with pathogenic VCP variants, the symptoms mainly present as behavioral-variant (bv) FTD and rarely as semantic dementia (SD). Various pathogenic VCP variants have been reported to cause bvFTD, whereas the only variant previously linked to SD is VCP p.Arg155Cys. Here, we report the case of a female Japanese patient with SD carrying the pathogenic VCP variant p.Arg191Gln. The patient developed naming difficulties, word-finding difficulties, stereotypical behavior, decreased spontaneity, and executive dysfunction at 55 years old and was diagnosed with SD at our hospital at 56 years old. At 59 years, there were no clinical findings suggestive of myopathy, pyramidal signs, or bone involvement. Genetic analyses, including whole-exome and Sanger sequencing, identified the VCP p.Arg191Gln variant in the patient with isolated SD. She required wheelchair assistance for 62 years and was mute. She later died from complications of malnutrition due to feeding difficulties. This case suggests that VCP variants may result in not only bvFTD but also SD, indicating a broader spectrum of FTLD-related phenotypes linked to pathogenic VCP variants.

BACKGROUND: No previous study has fully described older adults who make a first suicide attempt late in life. We retrospectively reviewed adults ≥ 60 years admitted to a university psychiatric ward after an attempt to (1) detail their demographic and clinical features; (2) compare admission and discharge diagnoses to measure diagnostic shifts-especially from major depressive disorder (MDD) to dementia; and (3) determine whether certain dementia subtypes, notably dementia with Lewy bodies (DLB), are over-represented. METHODS: Medical charts of patients transported to the emergency department and hospitalised between April 2015 and March 2024 were screened. After excluding cases with psychiatric disorders before the age of 60 years, 63 late-onset attempters were analysed. Diagnoses were reassessed with DSM-5-TR and standard neurodegenerative criteria; discrepancies were resolved by two senior psychiatrists. Mini-Mental State Examination scores, suicide methods and demographics were compared across final diagnoses. RESULTS: At discharge, psychiatric disorders predominated (65.1%), but dementia was present in 31.7%; DLB was the leading subtype (19.0%), followed by Alzheimer's disease (9.5%). Diagnostic revision was common: 17 patients (27.0%) changed diagnosis during hospitalisation, including 15 who shifted from MDD to dementia; 10 of these reclassifications were to DLB and six met criteria for psychiatric-onset DLB. Mini-Mental State Examination scores did not differ between MDD and DLB, although scores were lower in Alzheimer's disease. Suicide methods-most often drug overdose-showed no relation to diagnosis. CONCLUSIONS: Almost one-third of older first-time attempters harboured unrecognised dementia, most frequently DLB and over one-quarter of initial MDD diagnoses converted to dementia after full assessment. Brief cognitive screens alone missed these cases. Routine post-attempt care for older adults should therefore include informant history, detailed neuropsychological testing and dementia-specific biomarkers to guide targeted prevention and treatment.

BACKGROUND: Various neuropsychiatric symptoms are associated with caregiver burden in patients with dementia with Lewy bodies (DLB). However, the causal relationship between individual neuropsychiatric symptoms and caregiver burden in DLB has not been investigated in Japan. METHODS: This prospective observational study was conducted at four medical centres, including 30 patients with probable DLB aged ≥ 65 years who met the McKeith DLB diagnostic criteria. Caregiver burden and neuropsychiatric symptoms were assessed using the Japanese version of the Zarit Burden Interview (J-ZBI) and Neuropsychiatric Inventory Questionnaire, respectively. The participants were asked whether they had newly used a day service 6 months later. Data from the initial visits and the 6-month follow-ups were compared and analysed. RESULTS: At the initial visit, the mean age of individuals with DLB was 80.8 (5.8) years; their mean Mini-Mental State Examination score was 20.6 (5.1). J-ZBI scores significantly increased for participants with persistence or incidence of anxiety and apathy, compared with those without or with disappearance of these symptoms. Day service use did not affect the caregiver burden. The multiple regression analyses showed that changes in cognitive function and instrumental activities of daily living scores were not associated with changes in caregiver burden. The persistence or incidence of anxiety (β = 0.599, p < 0.001) and apathy (β = 0.587, p < 0.001) were also independently significantly associated with increased J-ZBI scores 6 months later. CONCLUSIONS: Persistence or incidences of anxiety and apathy may increase caregiver burden in patients with DLB. Clinicians should pay attention to these neuropsychiatric symptoms to prevent the worsening of caregiver burden. TRIAL REGISTRATION: UMIN Clinical Trials Registry: UMIN000051472.

OBJECTIVES: To clarify the characteristics of Japanese patients with frontotemporal dementia (FTD), we have established a nationwide multicenter registry named the Frontiers of Time course and Living specimen registry and Disease-modifying therapy development in Japanese patients with FTLD (FTLD-J). To ensure diagnostic consistency, we implemented case review meetings in the registry and evaluated their utility. METHODS: Between February 2016 and August 2024, 269 patients with behavioral variant FTD (bvFTD), semantic dementia (SD), or progressive nonfluent aphasia (PNFA) were registered. Fifteen case review meetings, open to all participating facilities, were held, where the clinical course, neuropsychiatric-neuropsychological evaluations, and neuroimaging analysis of 238 out of 269 cases were presented. Initial diagnoses were approved or revised based on discussions among specialists regarding whether the cases met the diagnostic criteria. We examined the diagnostic stability in participants initially diagnosed with bvFTD, SD, and PNFA. Given the limited number of PNFA cases, we compared the rate of diagnostic changes between bvFTD and SD using the chi-square test. RESULTS: Of the 126 participants enrolled as bvFTD, 75 were confirmed as bvFTD. In the remaining 51 patients, the diagnoses changed during the meeting. Of the 95 participants enrolled as SD, 77 were confirmed as SD, and in 18 cases, the diagnoses changed. Of the 17 participants enrolled as PNFA, 15 were confirmed as PNFA; bvFTD had a predominantly higher rate of diagnostic change than those with SD (p < 0.001). CONCLUSIONS: Our results suggested that case review meetings in a multicenter study may improve diagnostic consistency, especially in bvFTD.

Management of psychiatric symptoms in dementia with Lewy bodies (DLB) is challenging due to hypersensitivity to psychotropic medications. Electroconvulsive therapy (ECT) is a potential therapeutic option for DLB, but its efficacy and safety remain uncertain. We systematically reviewed articles on ECT for DLB, including those published in Japanese-language journals, and surveyed institutions certified by the Japanese Psychogeriatric Society. Of 41 peer-reviewed articles, 32 were from Japan. The proportion of prodromal DLB cases was significantly higher in Japan (34.8 %) than in other countries (9.5 %) (p = 0.044). Cardiac [123I]-metaiodobenzylguanidine scintigraphy and/or striatal dopamine transporter imaging were significantly more frequently in Japan (71.8 %) than in other countries (5.5 %) (p < 0.001). ECT has shown effectiveness in treating depression, catatonia, agitation and psychosis. It was generally considered safe, with transient delirium being the most common side effect, occurring in 16.1 % of Japanese cases. However, current evidence is limited to case studies and lacks randomized controlled trials. The survey confirmed that ECT is widely performed for DLB in Japan, although the number of cases treated varied greatly across institutions. These findings underscore the need for standardized ECT guidelines for DLB. Multicenter studies with standardized assessments and longitudinal follow-up are essential to further research on ECT for DLB, including psychiatric-onset prodromal DLB.

BACKGROUND: Delusional disorder, somatic type (DDST) is characterized by the presence of persistent delusions related to having a physical illness or bodily dysfunction, despite contradictory medical evidence. Antipsychotics like pimozide have shown efficacy in the treatment of DDST, and several case reports suggest that antidepressants may also be effective for this disorder. We are the first to report the effectiveness of escitalopram, which is a most selective and potent serotonin reuptake inhibitor, in a patient with DDST. CASE PRESENTATION: The case was a 62-year-old woman with DDST, presenting with oral somatic delusions. Escitalopram treatment (10 mg/day, increased to 20 mg/day) led to significant symptom improvement, and the symptoms of DDST had nearly resolved ∼5 weeks after the initiation of escitalopram. Single-photon emission computed tomography imaging during DDST symptoms showed reduced regional cerebral blood flow (rCBF) in the cerebral cortex, particularly in the temporal and parietal lobes, with follow-up imaging after 9 weeks of escitalopram treatment demonstrating rCBF improvement correlating with clinical recovery. CONCLUSION: This case suggests that escitalopram was effective in treating DDST, providing further support for the involvement of serotonergic dysfunction in the pathophysiology of DDST. The improvement in rCBF following treatment suggests that DDST may be associated with reduced rCBF in the temporal and parietal lobes.

OBJECTIVES: Managing symptoms, notably psychiatric symptoms, in dementia with Lewy bodies (DLB) is complex, affecting both patients and caregivers. People with DLB often react poorly to antipsychotics, limiting treatment options. Although electroconvulsive therapy (ECT)'s potential for DLB is acknowledged, evidence is scarce owing to limited studies. This study investigated ECT's effectiveness and safety for DLB and prodromal DLB with antecedent psychiatric symptoms. METHODS: This retrospective study investigated people with DLB (N = 12) and mild cognitive impairment (MCI) with LB (N = 13), a prodromal form of DLB, who underwent ECT for psychiatric symptoms and had abnormal findings confirmed using dopamine transporter single-photon emission computed tomography and 123I-metaiodobenzylguanidine myocardial scintigraphy. We reviewed these patients' medical records and determined the severity of psychotic symptoms before and 1 week after the final ECT session with the Clinical Global Impressions Severity Scale (CGI-S). Improvement in psychotic symptoms was evaluated approximately 1 week after the final ECT session using the CGI Improvement Scale (CGI-I). Additionally, we assessed cognitive function and dementia severity before and after ECT, as well as any adverse events caused by ECT. RESULTS: ECT significantly improved psychiatric symptoms, as assessed using the CGI-S, with CGI-I reports in the order of 60% "very much improved," 20% "much improved," 16% "minimally improved," and 4% "no change." Parkinsonism improved (Hoehn and Yahr: 1.76 ± 1.2 before vs. 1.04 ± 0.7 after, p < 0.001) as did dementia severity (Clinical Dementia Rating, p = 0.037). Adverse events included delirium in 24% of patients and amnesia in 4% of patients. ECT did not worsen cognitive function. CONCLUSIONS: ECT for DLB and MCI with LB with antecedent psychiatric symptoms appears safe and effective in managing psychiatric symptoms and Parkinsonism. Further large-scale multicenter studies are warranted to conclusively establish its effectiveness and safety.

BACKGROUND: Schizophrenia often involves persecutory delusions, which cause psychological distress. Some patients use online gaming as a coping tool. However, excessive online gaming has raised concerns about internet gaming disorders (IGD), while any soothing effects of online gaming on psychological distress remain unclear. Herein, we report changes in anxiety and IGD severity, measured using rating scales, in a patient with schizophrenia who used online gaming as a coping strategy for psychological distress. CASE PRESENTATION: A 43-year-old woman diagnosed with schizophrenia had worsening persecutory delusions, including that of being targeted by snipers, and had difficulty going out because of anxiety. She coped with her psychological distress using online shooting games. We assessed her state and trait anxiety, social anxiety, avoidance behavior when alone, and IGD severity. There was a notable reduction in the state anxiety score after the introduction of online gaming. The scores for trait anxiety, social anxiety, and avoidance behavior when alone decreased noticeably after the acquisition of coping strategies. This case demonstrates the presence of IGD only during the acquisition of coping strategies. CONCLUSION: This case highlights the potential of online gaming as a coping strategy for schizophrenia-related anxiety. However, excessive gaming can lead to IGD and thus necessitates caution. Further research should explore the applicability and potential risks of using online gaming to cope with psychological distress among patients with schizophrenia.

Loss-of-function (LoF) variants in the TANK binding kinase 1 (TBK1) gene are implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. In this study, we present the first familial cases of ALS and parkinsonism associated with a novel TBK1 variant. We describe two siblings: one diagnosed with classical ALS and the other with a unique syndrome overlapping ALS and parkinsonism. Comprehensive clinical and imaging evaluations supported these diagnoses. Genetic analysis through whole-genome sequencing revealed a previously unknown heterozygous splice site variant in TBK1. Functional assessments demonstrated that this splice site variant leads to abnormal splicing and subsequent degradation of the mutated TBK1 allele by nonsense-mediated decay, confirming its pathogenic impact. Our findings suggest a broader involvement of TBK1 in neurodegenerative diseases and underscore the need for further research into TBK1's role, advocating for screening for TBK1 variants in similar familial cases.

Dominantly inherited mutation D395G in the gene encoding valosin-containing protein causes vacuolar tauopathy, a type of behavioural-variant frontotemporal dementia, with marked vacuolation and abundant filamentous tau inclusions made of all six brain isoforms. Here we report that tau inclusions were concentrated in layers II/III of the frontotemporal cortex in a case of vacuolar tauopathy. By electron cryomicroscopy, tau filaments had the chronic traumatic encephalopathy (CTE) fold. Tau inclusions of vacuolar tauopathy share this cortical location and the tau fold with CTE, subacute sclerosing panencephalitis and amyotrophic lateral sclerosis/parkinsonism-dementia complex, which are believed to be environmentally induced. Vacuolar tauopathy is the first inherited disease with the CTE tau fold.

•A 77-year-old right-handed man experienced an infarct in the right midbrain.•Ipsilesional progressive micrographia occurred after the midbrain infarct.•Micrographia improved when the patient wrote as if practicing Japanese calligraphy.•Further studies should confirm the utility of Japanese calligraphy in such cases.

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a rare and severe autoimmune encephalitis that displays neuropsychiatric symptoms and autonomic instability, e.g., hypoventilation and cardiac arrhythmia. Severe arrhythmia including asystole associated with this encephalitis is rare. Several causes have been suggested. Nevertheless, no report of the literature has described examination by functional brain imaging of a patient with asystole during anti-NMDA receptor encephalitis. This case is that of a 34-year-old woman diagnosed as having anti-NMDA receptor encephalitis. She repeatedly showed 10-20 s asystole episodes necessitating a temporary transvenous pacemaker. After resection of the bilateral ovarian cystic tumor, her symptoms improved. Regional cerebral blood flow (rCBF) was evaluated using single-photon emission computed tomography. The rCBF was increased in the amygdala, hypothalamus, anterior cingulate, hippocampus, and anterior temporal lobes, but decreased in the dorsolateral frontal lobes, parietal lobes, and occipital lobes. Findings in this case suggest that altered rCBF in the patient with asystole episodes associated with anti-NMDA receptor encephalitis was observed in several brain lesions. The rCBF increases in the central autonomic networks, i.e., the amygdala, hypothalamus, and anterior cingulate, might be associated with dysregulation of sympathetic and parasympathetic nervous systems leading to asystole.

Cotard's syndrome is a rare clinical condition characterized by the presence of nihilistic delusions, delusions of immortality, depressive mood, and anxiety. Longitudinal changes in regional cerebral blood flow (rCBF) obtained under different conditions with and without Cotard's syndrome have rarely been reported in the literature. We report a case of a patient with Cotard's syndrome in whom longitudinal rCBF was assessed using single-photon emission computed tomography (SPECT). The patient was a 52-year-old man suffering from schizophrenia and mild mental retardation. He was transported to our hospital because of lumbar fractures caused by a suicidal attempt. In the second week after admission, he displayed Cotard's syndrome, i.e., nihilistic delusions, suicidal thoughts, and depressive mood. SPECT with 99mTc-ethyl cysteinate dimer was performed, and the rCBF increased in the bilateral prefrontal cortex but decreased in the occipital and parietal lobes. He was treated with pharmacotherapy mainly using lurasidone, and his Cotard's symptoms disappeared. SPECT was performed again. The increased rCBF in the bilateral prefrontal cortex and the decreased rCBF in the right occipital and parietal lobes were improved. The present case suggests that increased rCBF in the prefrontal cortex and decreased rCBF in the right occipital and parietal lobes are associated with the development of Cotard's syndrome.

Dementia with Lewy bodies (DLB) is strongly associated with Alzheimer disease (AD)-type pathology and tends to mask the core clinical features of DLB. Therefore, there may be cases of undiagnosed DLB without suggestive biomarkers of DLB. We describe the case of a 63-year-old woman who was initially diagnosed as having AD and later diagnosed with DLB based on suggestive biomarkers of DLB. In this case, transient sleep talking with physical movements for several days led to the assessment of suggestive biomarkers for DLB in the absence of the core clinical features of DLB. For clinicians, diagnosing DLB in patients with AD-type pathology is challenging. However, the application of biomarkers suggestive of DLB to all patients with dementia is not realistic. To overcome the difficulties of clinical diagnosis of DLB, further research is needed regarding strategies for the application of suggestive biomarkers for DLB to appropriately diagnose DLB.

Recoverin is a neuron-specific calcium-binding protein that is mainly located in the retina and pineal gland. Few reports have described patients with anti-recoverin antibody-positive encephalitis, and no cases of psychosis associated with this encephalitis have been reported. We report a patient with anti-recoverin antibody-positive encephalitis with Cotard and Capgras delusions who was successfully treated with electroconvulsive therapy (ECT). The patient was a 25-year-old woman. She exhibited disorientation, executive function deficits, tremors in the upper limbs, generalized athetoid-like involuntary movements, hallucinations, incontinence, and fever, which led to her admission to our hospital. Upon admission, she complained of Cotard delusions. Various diagnostic tests, including cerebrospinal fluid analysis, antibody screening, and brain imaging, were unremarkable, except for positivity for serum anti-recoverin antibodies, non-specific general slowing on electroencephalography and decreased regional cerebral blood flow (rCBF) in the frontal and occipital lobes, and increased rCBF in the basal ganglia and pons on single-photon emission computed tomography. She was eventually diagnosed with encephalitis positive for anti-recoverin antibodies and treated with immunoglobulins and steroids. Her neurological symptoms improved temporarily, but three months later, psychiatric symptoms, i.e., suicidal thoughts and Cotard and Capgras delusions, were exaggerated. After ECT, her condition significantly improved. In conclusion, the present report suggests that pineal gland dysfunction due to anti-recoverin antibody or its cross-reactivity with neuron-specific calcium-binding proteins may contribute to the neuropsychiatric symptoms observed in anti-recoverin antibody-positive encephalitis and that ECT can be a viable treatment option if immunotherapy proves ineffective. Additionally, decreased rCBF in the prefrontal cortex may be associated with the clinical features of Capgras and Cotard delusions.

BACKGROUND: Cerebrospinal fluid (CSF) area mask correction reduces the influence of low [123I]-N-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) nortropane (123I-FP-CIT) accumulation in the volume of interest (VOI) by CSF area dilatation on the specific binding ratio (SBR) calculated using the Southampton method. We assessed the effect of CSF area mask correction on the SBR for idiopathic normal pressure hydrocephalus (iNPH) characterized by CSF area dilatation. METHODS: We enrolled 25 patients with iNPH who were assessed using 123I-FP-CIT single-photon emission computed tomography (SPECT) before shunt surgery or the tap test. The SBRs with and without CSF area mask correction were calculated, and changes in quantitative values were verified. Additionally, the number of voxels in the striatal and background (BG) VOI before and after CSF area mask correction were extracted. The number of voxels after correction was subtracted from that before correction, and the volume removed by the CSF area mask correction was calculated. The volumes removed from each VOI were compared to verify their effect on SBR. RESULTS: The images of 20 and 5 patients with SBRs that were decreased and increased, respectively, by CSF area mask correction showed that the volumes removed from the BG region VOI were higher and lower, respectively than those in the striatal region. CONCLUSIONS: The SBR before and after CSF area mask correction was associated with the ratio of the volume removed from the striatal and BG VOIs, and the SBR was high or low according to the ratio. The results suggest that CSF area mask correction is effective in patients with iNPH. TRIAL REGISTRATION: This study was registered in the UMIN Clinical Trials Registry (UMIN-CTR) as UMIN study ID: UMIN000044826. 11/07/2021.

Quantification of in vivo reactive astrogliosis, which represents neural inflammation and remodeling in the brain, is an emerging methodology for the evaluation of patients with neurodegenerative diseases. [18F]THK-5351 is a positron emission tomography (PET) tracer for monoamine oxidase B (MAO-B), a molecular marker of reactive astrogliosis. We performed in vivo [18F]THK-5351 PET in a patient who at autopsy was found to have argyrophilic grain disease (AGD) with comorbid pathology to visualize reactive astrogliosis for the first time. We aimed to validate an imaging-pathology correlation using [18F]THK-5351 PET and the autopsy brain. The patient, a 78-year-old man, was pathologically diagnosed with AGD combined with limbic-predominant age-related transactive response DNA-binding protein of 43 kDa encephalopathy and Lewy body disease without Alzheimer disease-related neuropathological changes. Reactive astrogliosis in the postmortem brain was abundant in the inferior temporal gyrus, insular gyrus, entorhinal cortex, and ambient gyrus where premortem [18F]THK-5351 signals were high. We found a proportional correlation between the amount of reactive astrogliosis in the postmortem brain and the in vivo [18F]THK-5351 standardized uptake value ratio (r = 0.8535, p = 0.0004). These results indicated that reactive astrogliosis in AGD with comorbid pathology could be identified and quantified by in vivo MAO-B imaging.

In this issue, Sakurai et al. report on relevant findings for the clinical diagnosis of argyrophilic grain disease (AGD). Their study describes a characteristic atrophy distribution restricted to the limbic lobes, namely the ambient gyrus, in AGD versus Alzheimer's disease (AD), in pathologically confirmed patients using magnetic resonance imaging by voxel- and surface-based morphometry. Here, we discuss the possibility of employing functional or molecular brain imaging to further improvement of diagnosis of AGD. Additional research is required to elucidate the contributions of comorbid AD and transactive response DNA-binding protein 43 kDa pathologies in patients with AGD.

Cerebellar injuries can cause syntax impairments. Cortical dysfunction due to cerebello-cerebral diaschisis is assumed to play a role in this phenomenon. Functional magnetic resonance imaging studies have repeatedly shown the activation of Broca's area in response to syntactic tasks. However, there have been no reports of selective syntax impairment and hypoperfusion restricted to this area after cerebellar injury. We herein report a patient with right cerebellar hemorrhage that led to marked syntax impairment along with severe hypoperfusion confined to the Brodmann area (BA) 45 (anterior part of Broca's area) and BA46.

Semantic dementia (SD) is a unique clinicopathological entity associated with TDP-type C pathology. We present four cases of SD that illustrate the clinicopathological diversity of TDP-43 pathology, including early-onset cases of TDP-type C with corticospinal tract (CST) and motor neuron pathology and late-onset cases of TDP-type A with combined pathology. Case 1 was a 62-year-old man with semantic variant of primary progressive aphasia (svPPA) with left-predominant temporal atrophy and TDP-type C pathology with low Alzheimer's disease neuropathologic changes (ADNC). Case 2 was a 63-year-old woman with right-predominant temporal atrophy and TDP-type C pathology who had prosopagnosia and personality changes. Phosphorylated(p)-TDP-43-positive long dystrophic neurites (DNs) were observed throughout the cerebral cortex; they were more abundant in the relatively spared cortices and less so in the severely degenerated cortices. We observed CST degeneration with TDP-43 pathology in the upper and lower motor neurons, without apparent motor symptoms, in SD with TDP-type C pathology. Case 3 was a 76-year-old man who had svPPA and personality changes, with left-predominant temporal atrophy and TDP-type A pathology with high ADNC and argyrophilic grain (AG) stage 3. Case 4 was an 82-year-old man who had prosopagnosia and later developed symptoms of dementia with Lewy bodies (DLB) with right-predominant temporal atrophy and TDP-type A pathology with high ADNC, DLB of diffuse neocortical type, and AG stage 3. The distribution of p-TDP-43-positive NCIs and short DNs was localized in the anterior and inferior temporal cortices. An inverse relationship between the extent of TDP pathology and neuronal loss was also observed in SD with TDP-type A pathology. In contrast, the extent of AD, DLB, and AG pathology was greater in severely degenerated regions. CST degeneration was either absent or very mild in SD with TDP-type A. Understanding the clinicopathological diversity of SD will help improve its diagnosis and treatment.

BACKGROUND: Variants in the valosin-containing protein (VCP) gene were identified as one of the causes for inclusion body myopathy associated with Paget disease of the bone and frontotemporal dementia (FTD). Previously identified pathogenic variants in VCP are associated with frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) pathologically, but p.Asp395Gly VCP was recently reported to cause familial FTD with tauopathy characterized by neurofibrillary tau tangles (NFT) and not FTLD-TDP. We describe the clinical and genetic findings of a patient with p.Asp395Gly valosin-containing protein (VCP), who was diagnosed with FTD without a family history and in the absence of muscle or bone disease comorbidity. CASE PRESENTATION: The patient was a 62-year-old man, who developed atypical depression at the age of 37 years. Subsequently, he presented with self-centered behavior at the age of 45 years. The self-centered behavior intensified from around the age of 50 years, which was accompanied by the development of executive dysfunction; therefore, he visited our hospital at 52 years of age. Magnetic resonance imaging revealed bilateral frontal lobe atrophy. Brain perfusion single-photon emission computed tomography revealed bilateral frontal lobe hypoperfusion. The patient fulfilled the diagnostic criteria for behavioral variant of FTD. Ten years after the diagnosis, computed tomography of the trunk and limbs, muscle biopsy, and bone scintigraphy revealed the absence of concomitant muscle and bone disease. The concentrations of cerebrospinal fluid (CSF) total tau and phosphorylated tau proteins were 389 pg/mL and 53.2 pg/mL (cut-off: 50 pg/mL), respectively. Genetic analyses were performed using the whole-exome and Sanger sequencing methods. We identified p.Asp395Gly VCP in this patient with pure FTD. CONCLUSIONS: p.Asp395Gly VCP was identified in a patient with likely sporadic FTD without concomitant muscle and bone disease. The CSF analysis suggested that our patient may have FTD due to NFT accumulation similar to the familial FTD patients with p.Asp395Gly VCP recently reported. Our findings suggest that a genetic search for the pathogenic variants of VCP should be considered not only for familial FTD, but also for patients with sporadic FTD, even in the absence of comorbid muscle or bone disease.

<jats:p>Musical hallucinations (MHs) are a type of auditory hallucination in which music is perceived despite a lack of actual sound. Few reports have described longitudinal neuroimaging findings in different conditions before and during MHs. This report describes a depressed patient whose regional cerebral blood flow (rCBF) was assessed using single-photon emission computed tomography (SPECT) before and during MHs. A 72-year-old depressed woman was admitted to our hospital. During the treatment period, she experienced MHs. Then MHs disappeared with treatment of depression or following improvement in the mood. SPECT scans were performed to assess the levels of rCBF in several brain areas before and during MHs. During MHs, rCBF was increased in the basal ganglia, thalamus, amygdala, and parietal lobes. This report suggests that increased rCBF in multiple brain areas, especially in the basal ganglia and thalamus, might be related to the pathophysiology of MHs in depressed patients.</jats:p>