Myelin abnormalities in merosin-deficient congenital muscular dystrophy.

INTRODUCTION/AIMS: Merosin is a protein complex located in the basement membrane of skeletal muscles and laminin α2-containing regions of the central and peripheral nervous systems. However, because of the prominence of muscle-related symptoms, peripheral neuropathy associated with merosin-deficient congenital muscular dystrophy type 1A (MDC1A) has received little clinical attention. This study aimed to present pathological changes in intramuscular nerves of three patients with MDC1A and discuss their relationship with electrophysiological findings to provide new evidence of peripheral nerve involvement in MDC1A. METHODS: MDC1A was confirmed by clinical features, muscle biopsy, and genetic testing for variants in LAMA2. To clarify peripheral nerve involvement, we statistically evaluated electrophysiological and muscle pathology findings of intramuscular nerves. These findings were compared with those of age-matched boys with Duchenne muscular dystrophy (DMD) as controls with normal nerves. Nerve conduction studies (NCS) were performed before biopsy. Biopsied intramuscular nerves were examined with electron microscopy using g-ratio, which is the ratio of axon diameter to myelinated fiber diameter. RESULTS: The myelin sheaths were significantly thinner in MDC1A patients than in age-matched DMD patients, with a mean g-ratio of 0.76 ± 0.07 in MDC1A patients and 0.65 ± 0.14 in DMD patients (p < .0001). No neuropathic changes were identified in muscle pathology. Low compound muscle action potential amplitudes, positive sharp waves and fibrillation potentials, and low-amplitude motor unit potentials with increased polyphasia indicated myopathic changes; no neurogenic changes were seen. DISCUSSION: We postulate that the thin myelin associated with MDC1A reflects the role of merosin in myelin maturation.

Brain structural changes in alternating hemiplegia of childhood using single-case voxel-based morphometry analysis.

BACKGROUND AND PURPOSE: Alternating hemiplegia of childhood (AHC) is a rare neurodevelopmental disease caused by ATP1A3 mutations. Using voxel-based morphometry (VBM) analysis, we compared an AHC patient cohort with controls. Additionally, with single-case VBM analysis, we assessed the associations between clinical severity and brain volume in patients with AHC. MATERIALS AND METHODS: To investigate structural brain changes in gray matter (GM) and white matter (WM) volumes between 9 patients with AHC and 20 age-matched controls, VBM analysis was performed using three-dimensional T1-weighted magnetic resonance imaging. Single-case VBM analysis was also performed on nine patients with AHC to investigate the associations between the respective volumes of GM/WM differences and the motor level, cognitive level, and status epilepticus severity in patients with AHC. RESULTS: Compared with controls, patients with AHC showed significant GM volume reductions in both hippocampi and diffuse cerebellum, and there were WM reductions in both cerebral hemispheres. In patients with AHC, cases with more motor dysfunction, the less GM/WM volume of cerebellum was shown. Three of the six cases with cognitive dysfunction showed a clear GM volume reduction in the insulae. Five of the six cases with status epilepticus showed the GM volume reduction in hippocampi. One case had severe status epilepticus without motor dysfunction and showed no cerebellar atrophy. CONCLUSION: With single-case VBM analysis, we could show the association between region-specific changes in brain volume and the severity of various clinical symptoms even in a small sample of subjects.

A review of harmonization strategies for quantitative PET.

PET can reveal in vivo biological processes at the molecular level. PET-derived quantitative values have been used as a surrogate marker for clinical decision-making in numerous clinical studies and trials. However, quantitative values in PET are variable depending on technical, biological, and physical factors. The variability may have a significant impact on a study outcome. Appropriate scanner calibration and quality control, standardization of imaging protocols, and any necessary harmonization strategies are essential to make use of PET as a biomarker with low bias and variability. This review summarizes benefits, limitations, and remaining challenges for harmonization of quantitative PET, including whole-body PET in oncology, brain PET in neurology, PET/MR, and non-18F PET imaging. This review is expected to facilitate harmonization of quantitative PET and to promote the contribution of PET-derived biomarkers to research and development in medicine.

Monte Carlo simulation study to explore optimum conditions for Astatine-211 SPECT.

211At is a promising nuclide for targeted radioisotope therapy. Direct imaging of this nuclide is important for in vivo evaluation of its distribution. We investigated suitable conditions for single-photon emission computed tomography (SPECT) imaging of 211At and assessed their feasibility using a homemade Monte Carlo simulation code, MCEP-SPECT. Radioactivity concentrations of 5, 10, or 20 kBq/mL were distributed in six spheres in a National Electrical Manufactures Association (NEMA) body phantom with a background of 1 kBq/mL. The energy window, projection number, and acquisition time were 71-88 keV, 60, and 60 s, respectively, per projection. A medium-energy collimator and three low-energy collimators were tested. SPECT images were reconstructed using the ordered subset expectation maximization (OSEM) method with attenuation correction (Chang method) and scatter correction (triple-energy-windows method). Image quality was evaluated using the contrast-to-noise ratio (CNR) for detectability and the contrast recovery coefficient (CRC) for quantitavity. The low-energy, high-sensitivity collimator exhibited the best detectability among the four types of collimators, with a maximum CNR value of 43. In contrast, the low-energy, high-resolution collimator exhibited excellent quantitavity, with a maximum CRC value of 102%. Scatter correction improved the image quality. In particular, the CRC value almost doubled after scatter correction. The detection of spheres smaller than 20 mm in diameter was difficult. In summary, low-energy collimators were suitable for the SPECT imaging of 211At. In addition, scatter correction was extremely effective in improving the image quality. The feasibility of 211At SPECT was demonstrated for lesions larger than 20 mm.

Periodic cycles of seizure clustering and suppression in children with epilepsy strongly suggest focal cortical dysplasia.

AIM: We investigated characteristic seizure patterns in epilepsy caused by focal cortical dysplasia (FCD), which differ from epilepsy by other aetiologies in surgical cases with lesions on magnetic resonance imaging (MRI), then examined if these features were applicable to patients with epilepsy without any lesions on MRI. METHOD: We retrospectively studied clinicopathological features in 291 (143 females) children with epilepsy who had undergone resective surgery after comprehensive evaluation, including 277 cases with lesions on MRI (136 females, age at resection 0-17 years [mean 6 years 10 months, SD 5 years 7 months]) and 14 cases without any lesions on MRI (seven females, age 0-16 years [mean 7 years 8 months, SD 4 years 8 months]). RESULTS: Among 277 patients with lesions on MRI, 87 cases exhibited recurrent periodic cycles of seizure clustering (≥5 seizures/day for ≥1 week) and suppression (no seizures for ≥1 week); of these, 80 cases (92%) were pathologically diagnosed with FCD. Other pathologies included glial scar, hippocampal sclerosis, hemimegalencephaly, and cortical tuber in three, two, one, and one case respectively. All 14 patients without any lesions on MRI had significant recurrent periodic seizure cycles and FCD histopathologically. INTERPRETATION: Periodic seizure cycles characterized by clustering and suppression in patients with epilepsy strongly suggest the presence of FCD regardless of MRI findings, and comprehensive evaluations for epilepsy surgery should be proceeded.

Drug-resistant temporal lobe epilepsy due to middle fossa meningoencephalocele in a child: A surgical case report.

BACKGROUND: Meningoencephalocele (ME) of the temporal lobe through a bone defect in the middle cranial fossa is a rare known cause of refractory temporal lobe epilepsy (TLE). ME-induced drug-resistant TLE has been described in adults; however, its incidence in children is very rare. CASE REPORT: A 7-year-old girl presented at our hospital with brief episodes of impaired consciousness and enuresis. Initial brain MRI results were interpreted as normal. Her seizures could not be controlled even with multiple anti-seizure medications. She was diagnosed with drug-resistant TLE, which presented with prolonged impaired awareness seizures for 30-60 s and secondary bilateral tonic seizures. At 9 years of age, brain MRI revealed a left temporal anteroinferior ME with a congenital bone defect in the left middle cranial fossa. She was referred for presurgical epilepsy evaluation. Long-term video electroencephalography (EEG) failed to reveal regional abnormality in the left temporal lobe; invasive evaluation using stereoelectroencephalography (SEEG) was thus indicated. Ictal onset SEEG was identified in the temporal pole near the ME which was rapidly propagated to the mesial temporal structures and other cortical regions. The left temporal pole including the ME was micro-surgically disconnected while preserving the hippocampus and amygdala. The patient's seizures have been completely controlled for 1 year and 6 months post-operatively. CONCLUSION: SEEG revealed rapid propagation of ictal activity in this patient's case, confirming that the ME was epileptogenic. Since the majority of patients with refractory epilepsy caused by ME have favorable postoperative seizure outcomes, it is important to carefully check for ME in drug-resistant TLE patients with apparently normal MRI.

Genetic and clinical landscape of childhood cerebellar hypoplasia and atrophy.

PURPOSE: Cerebellar hypoplasia and atrophy (CBHA) in children is an extremely heterogeneous group of disorders, but few comprehensive genetic studies have been reported. Comprehensive genetic analysis of CBHA patients may help differentiating atrophy and hypoplasia and potentially improve their prognostic aspects. METHODS: Patients with CBHA in 176 families were genetically examined using exome sequencing. Patients with disease-causing variants were clinically evaluated. RESULTS: Disease-causing variants were identified in 96 of the 176 families (54.5%). After excluding 6 families, 48 patients from 42 families were categorized as having syndromic associations with CBHA, whereas the remaining 51 patients from 48 families had isolated CBHA. In 51 patients, 26 aberrant genes were identified, of which, 20 (76.9%) caused disease in 1 family each. The most prevalent genes were CACNA1A, ITPR1, and KIF1A. Of the 26 aberrant genes, 21 and 1 were functionally annotated to atrophy and hypoplasia, respectively. CBHA+S was more clinically severe than CBHA-S. Notably, ARG1 and FOLR1 variants were identified in 2 families, leading to medical treatments. CONCLUSION: A wide genetic and clinical diversity of CBHA was revealed through exome sequencing in this cohort, which highlights the importance of comprehensive genetic analyses. Furthermore, molecular-based treatment was available for 2 families.

13N-ammonia positron emission tomography-derived endocardial strain for the assessment of ischemia using feature-tracking in high-resolution cine imaging.

BACKGROUND: Assessing endocardial strain using a single 13N-ammonia positron emission tomography (PET) scan would be clinically useful, given the association between ischemia and myocardial deformation. However, no software has been developed for strain analysis using PET. We evaluated the clinical potential of feature tracking-derived strain values measured using PET, based on associations with the myocardial flow reserve (MFR). METHODS AND RESULTS: This retrospective study included 95 coronary artery disease patients who underwent myocardial 13N-ammonia PET. Semi-automatic measurements were made using a feature-tracking technique during myocardial cine imaging, and values were calculated using a 16-segment model. Adenosine-stressed global circumferential strain (CS) and global longitudinal strain (LS) values were compared with global MFR values. Stressed and resting global strain values were also compared. Global strain values were significantly lower in 39 patients with abnormal MFRs [< 2.0] than in 56 patients with normal MFRs [≥ 2.0]. The global CS values in the stressed state were significantly decreased than the resting state values in patients with abnormal MFRs. CONCLUSIONS: This study applied endocardial feature-tracking to 13N-ammonia PET, and the results suggested that blood flow and myocardial motility could be clinically assessed in ischemic patients using a single PET scan.

13 N-ammonia PET-derived right ventricular longitudinal strain and myocardial flow reserve in right coronary artery disease.

PURPOSE: We developed a feature-tracking algorithm for use with electrocardiography-gated high-resolution 13 N-ammonia positron emission tomography (PET) imaging, and we hypothesized it could be used to clarify the association between right ventricular (RV) longitudinal strain (LS) and right coronary artery (RCA) ischemia. The aim of this study was to investigate the association between the reduction of regional myocardial flow reserve (MFR) in RCA territories and PET-derived LS of the RV free wall. METHODS: Ninety-three patients with coronary artery stenosis > 50%, diagnosed by coronary computed tomography angiography, and 10 controls were retrospectively analyzed. RV-LS in the free wall was measured by a feature-tracking technique on the resting and stressed 13 N-ammonia PET images of horizontal long axis slices. The patients were sub-grouped according to regional MFR values at the territories of RCA, left anterior descending artery (LAD), and left circumflex coronary artery (LCx): RCA-MFR < 2.0 [n = 34], RCA-MFR ≥ 2.0 but MFR < 2.0 at LAD or LCx territories [n = 11], and MFR ≥ 2.0 for all territories [n = 48]. Stress and resting RV-LS were compared in each of the four groups. Multiple comparisons of RV-LS among the four groups were performed in the stress and resting state. RESULTS: Decreased stress RV-LS in patients with an RCA-MFR < 2.0 was observed. In the patients with MFR ≥ 2.0 for all territories, the stressed RV-LS was significantly increased compared to that in the resting state. Significantly decreased RV free wall LS during adenosine stress in patients with RCA-MFR < 2.0 was observed in the other three groups. CONCLUSIONS: We measured RV myocardial LS using feature tracking in cine imaging of 13 N-ammonia PET. The results of this study suggest that PET-derived stressed RV-LS is useful for detecting reduced RV myocardial motion due to ischemia in the RCA territory.

Usefulness of semi-quantitative analysis in 123I metaiodobenzylguanidine SPECT/CT for the differentiation of pheochromocytoma and cortical adenoma.

OBJECTIVE: 123I metaiodobenzylguanidine (MIBG) scintigraphy is a useful tool for the diagnosis of pheochromocytomas (PHEOs), but some PHEOs are difficult to differentiate from cortical adenoma (CA) or normal adrenal uptake by visual evaluation alone. A new semi-quantitative analysis using 123I MIBG SPECT/CT is thus expected. Herein, we introduce the tumor-to-liver count ratio (T/L) and the tumor-to-muscle count ratio (T/M). METHODS: We examined the cases of 21 patients with PHEOs (10 males, 11 females; age 24-80, median 61 years) and 23 patients with CA (15 males and 8 females, age 30-78, median 58 years). The visual scoring based on 123I MIBG planar images (planar score) and SPECT images (SPECT score) was used as the conventional evaluation. Using 123I MIBG SPECT/CT findings, we calculated the semi-quantitative values of the count ratio using the maximum or mean count of the tumor and the liver or muscle as the reference organ (T/Lmax, T/Lmean, T/Mmax and T/Mmean). Each evaluation of the PHEOs and CAs was compared, and the diagnosing performance was evaluated based on an ROC analysis. RESULTS: The area under curve (AUC) values were as follows: the planar score, 0.833; SPECT score, 0.813; T/Lmax, 0.986; T/Lmean, 0.975; T/Mmax, 0.955; and T/Mmean, 0.933. The AUC for T/Mmax was significantly higher than those of the planar score, and SPECT score by ROC analysis (p < 0.01 each). CONCLUSION: The semi-quantitative value of 123I MIBG SPECT/CT is more useful than the conventional visual evaluation for differentiating PHEOs from CAs.

Pathogenic variants in the survival of motor neurons complex gene GEMIN5 cause cerebellar atrophy.

Cerebellar ataxia is a genetically heterogeneous disorder. GEMIN5 encoding an RNA-binding protein of the survival of motor neuron complex, is essential for small nuclear ribonucleoprotein biogenesis, and it was recently reported that biallelic loss-of-function variants cause neurodevelopmental delay, hypotonia, and cerebellar ataxia. Here, whole-exome analysis revealed compound heterozygous GEMIN5 variants in two individuals from our cohort of 162 patients with cerebellar atrophy/hypoplasia. Three novel truncating variants and one previously reported missense variant were identified: c.2196dupA, p.(Arg733Thrfs*6) and c.1831G > A, p.(Val611Met) in individual 1, and c.3913delG, p.(Ala1305Leufs*14) and c.4496dupA, p.(Tyr1499*) in individual 2. Western blotting analysis using lymphoblastoid cell lines derived from both affected individuals showed significantly reduced levels of GEMIN5 protein. Zebrafish model for null variants p.(Arg733Thrfs*6) and p.(Ala1305Leufs*14) exhibited complete lethality at 2 weeks and recapitulated a distinct dysplastic phenotype. The phenotypes of affected individuals and the zebrafish mutant models strongly suggest that biallelic loss-of-function variants in GEMIN5 cause cerebellar atrophy/hypoplasia.

Estimation of the lower limits for feasible Ra-223 SPECT imaging: a Monte Carlo simulation study.

OBJECTIVES: Ra-223 is a promising radionuclide for the treatment of skeletal metastases in castration-resistant prostate cancer patients. This study aims to estimate the lower limits for feasible Ra-223 single-photon emission computerized tomography (SPECT) imaging using a Monte Carlo simulation study. METHODS: The SPECT images were produced on a homemade code: the Monte Carlo simulation of electrons and photons for SPECT (MCEP-SPECT). The National Electrical Manufacturers Association (NEMA) phantom with six hot spheres of diameters of 37, 28, 22, 17, 13, and 10 mm installed inside, was used. The background activity concentration was 0.6 kBq/mL, and the ratios of hot concentrations to the background (R HB) were 25, 20, 15, 10, and 5. When R HB was 15, the background concentrations of 1.5, 0.9, 0.3, and 0.15 kBq/mL were also tested. The energy window was 84 keV±10%. The number of projections was 60/360°, and the acquisition time was 60 s per projection. Two kinds of collimators: middle-energy general-purpose (MEGP) and high-energy general-purpose (HEGP), were examined. The SPECT images were evaluated based on two quantitative indexes: contrast-to-noise ratio (CNR) for detectability and contrast recovery coefficient (CRC) for quantitative accuracy. RESULTS: The CRC for the HEGP collimator was 35-40%, while the CRC for the MEGP collimator was 25-30%. The CNRs for the MEGP collimator were larger than those for the HEGP collimator. The CNRs of the hot spheres with diameters less than 22 mm were lower than 5.0 for both collimators, when R HB and the background concentration were 15 and 0.6 kBq/mL, respectively. Based on the obtained results, it was estimated that the lower limit of R HB for the detection of the hot sphere with a diameter of 37 mm would be approximately 20 if the background concentration is 0.05 kBq/mL. CONCLUSIONS: The MEGP collimator is superior in terms of detectability, while the HEGP collimator is superior in terms of quantitative accuracy. When the lesion size is small, the MEGP collimator may be favorable. Based on these results, the estimated lower limit of the activity concentration would be approximately 1 kBq/mL if the background concentration is 0.05 kBq/mL for a large lesion.

Monte Carlo simulation of the acquisition conditions for 177Lu molecular imaging of hepatic tumors.

OBJECTIVE: To examine the impact of acquisition time on Lutetium-177 (177Lu) single-photon emission computed tomography (SPECT) images using Monte Carlo simulation. METHODS: A gamma camera simulation based on the Monte Carlo method was performed to produce SPECT images. The phantom was modeled on a NEMA IEC BODY phantom including six spheres as tumors. After the administration of 7.4 GBq of 177Lu, radioactivity concentrations of the tumor/liver at 6, 24, and 72 h after administration were set to 1.85/0.201, 2.12/0.156, and 1.95/0.117 MBq/mL, respectively. In addition, the radioactivity concentrations of the tumor at 72 h after administration varied by 1/2, 1/4, and 1/8 when comparison was made. Acquisition times examined were 1.2, 1.5, 2, 3, 6, and 12 min. To assess the impact of collimators, SPECT data acquired at 72 h after the administration using six collimators of low-energy high-resolution (LEHR), extended low-energy general-purpose (ELEGP), medium-energy, and general-purpose (MEGP-1, MEGP-2, and MEGP-3) and high-energy general-purpose (HEGP) were examined. After prefiltering using a Butterworth filter, projection images were reconstructed using ordered subset expectation maximization. The detected photons were classified into direct rays, scattered rays, penetrating rays, and characteristic X-rays from lead. The image quality was evaluated through visual assessment, and physical assessment of contrast recovery coefficient (CRC) and contrast-to-noise ratio (CNR). In this study, the CNR threshold for detectability was assumed to be 5.0. RESULTS: To compare collimators, the highest sensitivity was observed with ELEGP, followed by LEHR and MEGP-1. The highest ratio of direct ray was also observed in ELEGP followed by MEGP-1. In comparison of the radioactivity concentration ratios of tumor/liver, CRC and CNR were significantly decreased with smaller radioactivity concentration ratios. This effect was greater with larger spheres. According to the visual assessment, the acquisition time of 6, 6, and 3 min or longer was required using ELEGP collimator at 6, 24, and 72 h after administration, respectively. Physical assessment based on CNR and CRC also suggested that 6, 6, and 3 min or longer acquisition time was necessary at 6, 24, and 72 h after administration. CONCLUSION: 177Lu-SPECT images generated via the Monte Carlo simulation suggested that the recommended acquisition time was 6 min or longer at 6 and 24 h and 3 min or longer at 72 h after administration.

Linear cortical cystic lesions: Characteristic MR findings in MELAS patients.

BACKGROUND: Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) is a progressive neurodegenerative disorder with stroke-like lesions. The common MRI findings are gyral swelling and high signal intensity on T2WI/FLAIR images crossing the vascular territories. We have observed a linear cystic lesion and a laminar necrosis in the affected cortices of MELAS patients. Herein, we evaluated these cortical MRI findings in each subtype of mitochondrial disease. PATIENTS AND METHODS: We retrospectively reviewed the MRI findings of 71 consecutive patients with clinically and genetically confirmed mitochondrial diseases. The cortical cystic lesions and laminar necrotic lesions were evaluated on T1, T2, and FLAIR images in each subtype of mitochondrial disease, as were their clinical and other imaging characteristics. RESULTS: The cortical cystic lesion was observed in 21 of the 71 patients (29.6%) with mitochondrial diseases. Laminar necrosis was detected in only three patients (4.2%). MELAS was the most frequent subtype with cortical cystic lesions, accounting for 81.0%, and all showed the linear pattern except for one patient whose pattern was beaded-like. CONCLUSION: A cortical linear cystic lesion was a common MRI finding in our series of patients with mitochondrial disease, especially in those with MELAS, but laminar necrosis was not. These findings can help differentiate MELAS from infarction.

123I metaiodobenzylguanidine (MIBG) uptake predicts early relapse of neuroblastoma using semi-quantitative SPECT/CT analysis.

OBJECTIVE: 123I metaiodobenzylguanidine (MIBG) scintigraphy is a useful tool for the diagnosis of neuroblastoma (NB). MIBG uptake is correlated with norepinephrine transporter expression; hence, it is expected that high-MIBG tumors would be more highly differentiated and have a better prognosis than those with lower expression. We have introduced a method of assessing MIBG accumulation semi-quantitatively using SPECT/CT fusion images. The purpose of this study was to evaluate the relationship of 123I MIBG uptake measured by semi-quantitative values of SPECT/CT and early relapse of NB. METHODS: We studied the cases of 11 patients (5 males and 6 females, age 5-65 months, median age 20 months) with histopathologically proven NB between April 2010 and March 2015. The early-relapse group was defined as patients who had relapsed within 3 years after the first 123I MIBG SPECT/CT exam. Other patients were classified as the delay-relapse group. Uptake of MIBG was evaluated using the count ratio of tumor and muscles. T/Mmax and T/Mmean were defined as follows: T/Mmax = max count of tumor/max count of muscle, T/Mmean = mean count of tumor/mean count of muscle. RESULTS: The average T/Mmean values of the early-relapse group and delay-relapse group were 2.65 ± 0.58 and 7.66 ± 2.68, respectively. The T/Mmean values of the early-relapse group were significantly lower than those of delay-relapse group (p < 0.05). The average T/Mmax of the early-relapse group and delay-relapse group were 8.86 ± 3.22 and 16.20 ± 1.97, respectively. There was no significant difference in T/Mmax values between the two groups. CONCLUSIONS: Low 123I MIBG uptake using semi-quantitative SPECT/CT analysis was correlated with early relapse of NB.

Improvement of brain function after surgery in infants with posterior quadrant cortical dysplasia.

OBJECTIVE: To reveal whether neurodevelopmental outcome of infants after epilepsy surgery can be quantitatively assessed by electroencephalography (EEG) functional connectivity analysis. METHODS: We enrolled 13 infants with posterior quadrant dysplasia aged <2 years who were treated using posterior quadrantectomy and 21 age-matched infants. EEG was performed both before and one year after surgery. Developmental quotient (DQ) was assessed both before and 3 years after surgery. The phase lag index (PLI) of three different pairs of electrodes in the nonsurgical hemisphere, i.e., the anterior short distance (ASD), posterior short distance (PSD), and long distance (LD) pairs, were calculated as indices of brain connectivity. The relationship between the PLI and DQ was evaluated. RESULTS: Overall, 77% infants experienced seizure freedom after surgery. The beta- and gamma- range PLI of PSD pairs increased preoperatively. All these pairs normalized postoperatively. Simple linear regression analysis revealed a significant relationship between the postoperative DQ and the postoperative beta-band PLI of ASD pairs. CONCLUSION: Preoperative abnormal hyper-connectivity was normalized to the control level after surgery. The postoperative hyperconnectivity was associated with long-term neurodevelopmental improvement. SIGNIFICANCE: PLI quantifies neurodevelopmental improvements after posterior quadrantectomy.

Clinical practice guidelines for high-resolution breast PET, 2019 edition.

Breast positron emission tomography (PET) has had insurance coverage when performed with conventional whole-body PET in Japan since 2013. Together with whole-body PET, accurate examination of breast cancer and diagnosis of metastatic disease are possible, and are expected to contribute significantly to its treatment planning. To facilitate a safer, smoother, and more appropriate examination, the Japanese Society of Nuclear Medicine published the first edition of practice guidelines for high-resolution breast PET in 2013. Subsequently, new types of breast PET have been developed and their clinical usefulness clarified. Therefore, the guidelines for breast PET were revised in 2019. This article updates readers as to what is new in the second edition. This edition supports two different types of breast PET depending on the placement of the detector: the opposite-type (positron emission mammography; PEM) and the ring-shaped type (dedicated breast PET; dbPET), providing an overview of these scanners and appropriate imaging methods, their clinical applications, and future prospects. The name "dedicated breast PET" from the first edition is widely used to refer to ring-shaped type breast PET. In this edition, "breast PET" has been defined as a term that refers to both opposite- and ring-shaped devices. Up-to-date breast PET practice guidelines would help provide useful information for evidence-based breast imaging.

ATP1A3 variants and slowly progressive cerebellar ataxia without paroxysmal or episodic symptoms in children.

A heterogeneous spectrum of clinical manifestations caused by mutations in ATP1A3 have been previously described. Here we report two cases of infantile-onset cerebellar ataxia, due to two different ATP1A3 variants. Both patients showed slowly progressive cerebellar ataxia without paroxysmal or episodic symptoms. Brain magnetic resonance imaging revealed mild cerebellar cortical atrophy in both patients. Whole exome sequencing revealed a de novo heterozygous variant in ATP1A3 in both patients. One patient had the c.460A>G (p.Met154Val) variant, while the other carried the c.1050C>A (p.Asp350Lys) variant. This phenotype was characterized by a slowly progressive cerebellar ataxia since the infantile period, which has not been previously described in association with ATP1A3 variants or in ATP1A3-related clinical conditions. Our report contributes to extend the phenotypic spectrum of ATP1A3 mutations, showing paediatric slowly progressive cerebellar ataxia with mild cerebellar atrophy alone as an additional clinical presentation of ATP1A3-related neurological disorders.

Postoperative improvement of executive function and adaptive behavior in children with intractable epilepsy.

INTRODUCTION: An alteration in postoperative cognitive function varies according to the patients' background characteristics, such as etiology, focus, and seizure duration. Accurate prediction and assessment of postoperative cognitive function is difficult in each patient. Adaptive behavior could describe the typical performance of daily activities and represents the ability to translate cognitive potential into real-world skills. We examined the relationship between alterations of executive function (EF) and adaptive behavior in school children undergoing surgery for intractable epilepsy. METHODOLOGY: We enrolled 31 children with focal resection or corpus callosotomy for intractable epilepsy [mean age at surgery, 12.5 years; 16 boys; mean intellectual quotient, 73.3]. We surveyed answered questionnaires on attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and adaptive behavior using the Vineland Adaptive Behavior Scale, 2nd edition (VABS-II), and performed continuous performance tests (CPTs) on children pre- and postoperatively. RESULT: ADHD and ASD symptoms improved after epilepsy surgery. The omission error (OE) in the CPT variable improved after epilepsy surgery, especially in children with a shorter preoperative period. Improved ASD symptoms led to an increased score of the coping skills subdomain. The reduced OE observed after surgery also increased the score of the community skills subdomain. CONCLUSION: Improvement in EF and ASD symptoms resulted in better adaptive behavior postoperatively. These results were important for the pre- and postoperative evaluation and re-evaluation of children with epilepsy requiring special education and related services.