Application of Suggestive Biomarkers in Dementia With Lewy Bodies With Masking of Typical Clinical Symptoms by Alzheimer Disease-type Pathology.

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.

Effect of cerebrospinal fluid area mask correction on 123I-FP-CIT SPECT images in idiopathic normal pressure hydrocephalus.

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.

Clinicopathological diversity of semantic dementia: Comparisons of patients with early-onset versus late-onset, left-sided versus right-sided temporal atrophy, and TDP-type A versus type C pathology.

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.

Valosin-containing protein Asp395Gly mutation in a patient with frontotemporal dementia: a case report.

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.

Clinicopathological heterogeneity of Alzheimer's disease with pure Alzheimer's disease pathology: Cases associated with dementia with Lewy bodies, very early-onset dementia, and primary progressive aphasia.

We report four cases depicting the heterogeneity of Alzheimer's disease (AD) associated with pure AD pathology. Case 1 was a 77-year-old man with a false positive diagnosis of dementia with Lewy bodies with reduced dopamine transporter uptake activity of the striatum but no Lewy body pathology. There were tau deposits in the large neurons in the putamen, which may be related to the development of parkinsonism. Case 2 was an AD patient in his early 30s who presented with a psychotic episode and a cognitive decline, and later developed myoclonus and seizures. He demonstrated considerable amyloid-beta deposits in the cerebral cortex, including cotton wool plaques, basal ganglia, and cerebellum. Tau deposits were also abundant in the cerebral neocortex, hippocampus, basal ganglia, and brain stem. Case 3 was a 60-year-old woman who exhibited typical symptoms characteristic of the logopenic variant of primary progressive aphasia (lvPPA). Case 4 was a 68-year-old man who exhibited the semantic variant of primary progressive aphasia (svPPA) plus repetition impairment, a rare case associated with AD pathology. In addition to tau pathology, astrocytic pathology was prominent in the white matter and cortical layers of the left temporoparietal cortices. While the main AD lesion in case 4 was evaluated by tau accumulation and astrogliosis in the left temporal lobe, that in case 3 in was evaluated by the same points in the left parietal lobe. Within the spectrum of lvPPA, case 4 may be regarded as a temporal variant of lvPPA presenting svPPA. The pathology of PPA associated with AD may have broader clinical manifestations than that in previously described cases. Case 4 also showed pathological features characteristic of cerebral amyloid angiopathy throughout the cerebral cortex. The distribution of tau and astrocytic pathologies in the cerebral cortex, basal ganglia, brain stem, and cerebellum may explain the various symptoms of atypical pure AD patients.

Comparison of the decreases in regional cerebral blood flow in the posterior cingulate cortex, precuneus, and parietal lobe between suspected non-Alzheimer's disease pathophysiology and Alzheimer's disease.

BACKGROUND: Suspected non-Alzheimer's disease pathophysiology (SNAP) shows Alzheimer's disease (AD)-like neurodegeneration; however, amyloid ß, which is a biological marker in AD, remains within normal levels. Since the effectiveness of anti-dementia drugs for AD on SNAP is unknown, it is important to distinguish between patients with SNAP and AD. We aimed to compare decreases in regional cerebral blood flow (rCBF) of the posterior cingulate cortex (PCC), precuneus, and parietal lobe critical to AD between SNAP and AD groups using the easy Z-score imaging system in single-photon emission computed tomography (eZIS-SPECT). METHODS: We retrospectively analysed eZIS-SPECT data of 13 SNAP and 24 AD patients. The three indicators (severity, extent, and ratio) that distinguished AD patients from healthy controls in previous studies were automatically calculated and were compared between the SNAP and AD groups. Receiver operating characteristic curve analysis and the area under the curve (AUC) were used to evaluate the diagnostic performance of the three indicators of eZIS in discriminating between the two groups. RESULTS: The mean values of severity, extent, and ratio were significantly lower in the SNAP group than in the AD group (P = 0.024, P = 0.044, and P = 0.045, respectively). The AUC values for severity, extent, and ratio were 0.668, 0.683, and 0.692, respectively. CONCLUSIONS: The present study suggests that SNAP shows milder reduction of rCBF in the PCC, precuneus, and parietal lobe as compared to AD. However, it may be difficult to distinguish between SNAP and AD with the degrees of decrease in rCBF in these regions.

Axillary Osmidrosis: Past, Present, and Future.

Axillary osmidrosis is characterized by offensive odor resulting from bacterial decomposition of apocrine secretions in the axillae, and individuals with axillary osmidrosis suffer detrimental effects to their psychosocial functioning. We searched the literature in January 2019 for all English-language publications discussing axillary osmidrosis to identify previous reports, present trends, and emerging treatments. Studies were listed chronologically by the country of the first author's institution. Publications were also classified regarding the study type (literature review), pathophysiology, and treatments. We identified 133 publications on axillary osmidrosis, and of these, 120 were from East-Asian countries. Before 1990, there were only 9 publications, but after 2000, publications increased in number. One hundred of 133 reports discussed treatment, namely, 39 reports on suction curettage, 28 reports on open surgery, and 8 reports on subdermal laser. Other studies focused on the pathophysiology of axillary osmidrosis. This literature review revealed unique trends in the identified studies. Because control of axillary odor is a universal subject, the etiology and pathophysiology of axillary osmidrosis have been studied throughout the world and are clearly described. However, almost all studies of surgical treatments have been performed in East-Asian countries. After the year 2000, various surgical and nonsurgical treatments, namely, laser therapy and suction curettage, have been attempted. Emerging treatments for axillary osmidrosis include ethanol injections, microwave therapy, and microneedle radiofrequency technologies; however, further studies of these treatments are needed.

Three-Dimensional Measurement of the Lateral Lip Element Sacrificed in Primary Repair of a Unilateral Cleft Lip.

BACKGROUND: In most children with a unilateral cleft lip (UCL), because lateral lip tissue on the cleft side is congenitally short, the lateral lip element should be appropriately excised during primary cheiloplasty so that symmetric nasolabial features are obtained after surgery. The purpose of this study was to measure how much of the lateral lip element is removed during primary cheiloplasty and compare the amount of sacrifice between different incision designs. METHODS: Preoperative 3-dimensional images of 50 infants with UCL were randomly selected. The incision designs of 3 representative techniques (Millard, Onizuka, and Fisher) were drawn on the images that were obtained before the primary repair. The lateral lip tissue excised by each technique was estimated as a percentage of the surface area of the sacrificed lateral lip to the entire lateral lip of the cleft side. RESULTS: In the case of incomplete UCL, the median values (range) were 3.2% (1.1%-5.9%), 11.6% (8.3%-20.1%), and 27.2% (15.1%-42.3%) for the Millard, Onizuka, and Fisher repairs, respectively. In cases of complete UCL, no sacrifice was needed for the Millard repair, whereas the median values (range) were 10.6% (5.2%-28.9%) and 22.5% (11.5%-48.6%) for the Onizuka and Fisher repairs, respectively. In Millard repair, the median values (range) of the lateral lip element that was resected before skin closure according to the "cut-as-you-go" policy were 5.8% (2.2%-11.8%) in cases with an incomplete UCL and 4.9% (2.7%-9.1%) in cases with a complete UCL. CONCLUSIONS: Our study demonstrated that sacrifice of the lateral lip element was minimal in the Millard repair, whereas it could exceed 20% in the Fisher repair. However, additional sacrifice of the advancement flap was needed in the Millard-type repair. The ratio of the lateral lip sacrifice varied between patients. Although UCL repair techniques should not be evaluated with the sacrifice ratio, excessive sacrifice of the lateral lip tissue can complicate the secondary lip correction. We recommend that surgeons estimate preoperatively how much lateral lip element will be sacrificed with each incision design using a 3-dimensional image for each child with a UCL.

Change in Incisional Design in Primary Unilateral Cleft Lip Repair Under General Anesthesia.

Nasolabial features of infants with unilateral cleft lip (UCL) are different when they are under general anesthesia for lip repair compared to when they are awake. This study aimed to investigate changes in the incisional design of cheiloplasty according to patient position and anesthesia: upright and awake versus supine and under general anesthesia. Three-dimensional images of 20 infants with UCL were randomly selected. Two different incisional designs were drawn on the images captured while the infants were awake. Those incisional designs were anthropometrically compared to the designs drawn on the images captured while the infants were under general anesthesia. Under general anesthesia, vermillion height of both the medial and lateral sides of the cleft became significantly greater. In the rotation-advancement design, the incisional line of the rotation flap on the medial lip element became significantly shorter under general anesthesia, whereas the advancement flap on the lateral lip element was not significantly altered. In an anatomical subunit approximation, both lengths of the philtral ridge on the noncleft side and incisional line along the philtral ridge on the cleft side became significantly shorter under general anesthesia, but these alterations did not affect the calculation of the width of the small triangular flap on the lateral lip element. These changes in nasolabial features after general anesthesia may cause surgical error, which result in secondary cleft lip deformities. However, because these changes varied among infants, preoperative planning using three-dimensional facial images of infants who are awake may be able to avoid surgical error.

Incidence of Secondary Lip Correction for Children With Unilateral Cleft Lip: A Single-Center Retrospective Study.

BACKGROUND: Numerous reports have described the incidence of secondary lip correction for patients with cleft lip (CL), and this incidence broadly varies among centers. The purpose of this study was to determine this revision rate for a reasonably large number of patients in our center and identify the clinical factors that contribute to the revision rate. METHODS: A retrospective chart review was conducted for all infants with unilateral CL with or without cleft palate who underwent primary cheiloplasty at our cleft center from 2006 to 2012. Four surgeons were in charge of almost all operations. We investigated how many children underwent lip revisions by the end of 2017. RESULTS: In total, 490 infants underwent primary lip repair, and 47 underwent revision surgery by the age of 8 years. Half of them (24 children) underwent revisions at the age of 5 or 6 years. There was no significant difference in the revision rate by sex or cleft side. The revision rate in children with CL only tended to be lower than that in children with alveolar cleft or cleft palate, but it was not significantly associated with the cleft type. The revision rate ranged from 2.8% to 15.2% among surgeons. CONCLUSIONS: The overall revision rate was 9.6%, which is relatively lower than that in other cleft centers. However, the repair technique and cleft care program should not be evaluated using the revision rate only. Various factors, including surgeons' preference, contribute to the indications for revision, and these factors can change with age. We plan to follow up the patients until our completion of the cleft care program and report the final revision rate.

Longitudinal Follow-up of Individuals With Cleft Lip Using Three-Dimensional Stereophotogrammetry.

The usefulness of three-dimensional (3D) stereophotogrammetry for treating cleft lip (CL) has been well documented. However, there are only a few reliable anthropometric analyses in infants with CL because at this age they cannot assume a resting facial position. Since 2014, we have used a handheld 3D imaging system in the operating room to obtain optimal images of infants with CL and palate under general anesthesia. Currently, 168 infants with a unilateral cleft, 50 infants with bilateral clefts, and 47 infants with an isolated cleft palate are being followed up in this way for a maximum of 30 months. Most patients ≥3 years of age are cooperative and allow staff to obtain 3D images without sedation. We plan to follow them until adulthood, obtaining 3D images at every intervention. Each year, >150 infants can be added to this ongoing longitudinal study. Using an archive of these digital images, various retrospective studies can be attempted in the future, which include comparisons of the long-term outcomes of various surgical techniques and interventions at different time intervals. This is the first 2-year preliminary report of a 20-year longitudinal study.

Use of a plastic eraser for ear reconstruction training.

BACKGROUND: Microtia reconstruction is a challenging procedure, especially in developing nations. The most complex part is learning how to fabricate a framework from costal cartilage. We herein propose a training regimen for ear reconstruction with the use of a plastic eraser. MATERIALS AND METHODS: The texture of a plastic eraser made from polyvinyl chloride is similar to that of human costal cartilage. The first step of the training is carving out the sixth through eighth rib cartilages from a block of plastic eraser. The second step is a fabrication of the framework from plastic rib cartilages, referring to a template from the intact auricle. RESULTS: As plastic erasers are inexpensive and universally available, inexperienced surgeons can repeatedly perform this framework training. Following several of these training sessions in developing nations, the co-authors and local surgeons successfully performed their microtia reconstructions in a reasonable operative time. CONCLUSIONS: This realistic carving model allows surgeons to gain experience before performing an actual ear reconstruction, even in resource-constrained circumstances.

Nasolabial Growth in Individuals With Unilateral Cleft Lip and Palate: A Preliminary Study of Longitudinal Observation Using Three-Dimensional Stereophotogrammetry.

There are limited numbers of studies comparing the preoperative and postoperative facial features of infants with unilateral cleft lip and palate (UCLP) using three-dimensional (3D) stereophotogrammetry. The authors attempted an anthropometric analysis of nasolabial asymmetry 1 year after primary lip repair using a handheld 3D imaging system. Five different nasolabial dimensions in 24 infants with UCLP were measured using 3D images captured during primary lip repair and again, 1 year after the repair. The nasal and upper-lip elements of the cleft side were significantly changed after primary lip repair, and nasolabial asymmetry was anthropometrically improved. This is a preliminary longitudinal observation of nasolabial growth in individuals with UCLP using 3D stereophotogrammetric technique. The authors would like to follow these children until adulthood, capturing 3D images at every intervention.

Chronic Expanding Hematoma Following Abdominoplasty.

Chronic expanding hematoma (CEH) is a relatively rare complication of trauma or surgery. We report a patient with CEH as a late complication of abdominoplasty. A 58-year-old woman underwent conventional abdominoplasty and thereafter refused to use a compression binder, citing discomfort. One month postoperatively, she presented with a gradually enlarging, painful abdominal mass. The results of ultrasonography and computed tomography were highly suspicious for CEH. The lesion was completely removed, together with surrounding fibrous tissue. Histopathology revealed a chronic hemorrhage collection with a fibrous capsule, consistent with CEH. This condition as a late complication of abdominoplasty has not previously been reported in the literature. However, an online medical consultation site features several abdominoplasty patients asking about persistent hematomas that sound suspicious for CEH. CEH might be underdiagnosed by surgeons. Although a postoperative binder may increase the risk of skin necrosis and deep vein thrombosis, appropriate compression treatment is necessary to prevent hematoma formation. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .