Episodic ataxia type 2 with a novel missense variant (Leu602Arg) in CACNA1A.

Autosomal dominant episodic ataxia type 2 (EA2) is caused by variants in CACNA1A. We examined a 20-year-old male with EA symptoms from a Japanese family with hereditary EA. Cerebellar atrophy was not evident, but single photon emission computed tomography showed cerebellar hypoperfusion. We identified a novel nonsynonymous variant in CACNA1A, NM_001127222.2:c.1805T>G (p.Leu602Arg), which is predicted to be functionally deleterious; therefore, this variant is likely responsible for EA2 in this pedigree.

18F-FDG PET/CT imaging of IgG4-producing MALT lymphoma with multiple site involvement.

18F-FDG PET/CT is regarded as a modality utilized for the purpose of lesion localization, staging and assessment of treatment response in patients with lymphoma. However, it is difficult that we diagnose among multifocal lymphoma, IgG4-related disease (IgG4-RD), or a combination of both conditions when confronted with multiple sites of 18F-FDG uptake with heightened serum IgG4 levels. We present a case of a 72-year-old male who was suspected of Sjögren's syndrome based on symptoms of xerostomia accompanied by swelling of the bilateral upper eyelid and salivary glands. Following a diagnostic biopsy that revealed mucosa-associated lymphoid tissue (MALT) lymphoma as a possible finding, 18F-FDG PET/CT was conducted, which demonstrated multiple sites of 18F-FDG accumulation. While multifocal MALT lymphoma was initially suspected, the coexistence of IgG4-RD could not be definitively ruled out due to the elevated serum IgG4 levels. Subsequent histopathological and immunohistochemical examinations confirmed the diagnosis of IgG4-producing MALT lymphoma. After receiving systemic therapy with rituximab, the swelling of the bilateral upper eyelid and parotid glands resolved upon visual examination, and the serum IgG4 levels returned to within the normal range in a few months. No new lesions were detected during the subsequent follow-up examinations conducted over a period of 3 years.

Effectiveness of 18F-FDG PET/CT in finding lung metastasis from a retroperitoneal paraganglioma.

A 50-year-old woman was diagnosed with iron deficiency anemia on general medical examination. Further, contrast-enhanced abdominal CT and magnetic resonance imaging revealed a large hypervascular mass with internal degeneration and necrosis in the retroperitoneal space. She was referred to our hospital for further evaluation and treatment. Because the paraganglioma was most likely as the imaging diagnosis, 123I-MIBG scintigraphy was performed. It revealed the marked abnormal accumulation in the retroperitoneal lesion indicating the paraganglioma and no other abnormal accumulation was noted. Several plasma catecholamines and their urinary metabolites were normal. On the subsequent 18F-FDG PET/CT, high FDG uptake was found in the retroperitoneal lesion (SUVmax=38). FDG uptake was also found in a small nodule at the base of the lower lobe of the right lung (SUVmax= 9.8). Contrast-enhanced imaging revealed a hypervascular nodule at the base of the right lung, suggesting pulmonary metastasis of a paraganglioma. The abdominal lesion and right lung nodule were excised, and retroperitoneal paraganglioma and pulmonary metastasis were diagnosed based on the pathology findings. In this case, 18F-FDG PET/CT was useful in the search for paraganglioma metastasis. We report a relationship between 123I-MIBG accumulation and 18F-FDG uptake in paraganglioma and review the relevant literature.

Effects of olmesartan and amlodipine on blood pressure, endothelial function, and vascular inflammation.

BACKGROUND: Anti-hypertensive drugs can improve vascular endothelial function. However, the mechanism remains to be elucidated. OBJECTIVES: This study sought to investigate mechanisms of anti-hypertensive drugs on improvement of vascular endothelial function in patients with essential hypertension. METHODS: Forty-five patients (mean age 58.5 ± 11.2 years) with uncontrolled essential hypertension were randomly assigned to receive olmesartan, an angiotensin II type 1 receptor blocker (ARB) (N = 23), or amlodipine, a calcium channel blocker (CCB) (N = 22), for 6 months. Endothelial function was evaluated by flow-mediated dilatation (FMD) of the brachial artery. Vascular inflammation was measured by blood-normalized standardized uptake value, known as a target-to-background ratio (TBR) within the carotid arteries using 18F-fluorodeoxyglucose-positron emission tomography combined with computed tomography. RESULTS: There were no significant differences of baseline clinical data between the ARB and CCB groups. Both anti-hypertensive drugs comparably lowered blood pressure and increased %FMD. TBR values were reduced by olmesartan (P < .001), while blood pressure variability was decreased by amlodipine (P = .004). Changes in %FMD from baseline (Δ%FMD) were inversely associated with ΔTBR in the olmesartan group (r = - .606, P = .003) and with Δsystolic blood pressure variability in the amlodipine group (r = - .434, P = .039). CONCLUSION: Our study indicated that olmesartan and amlodipine could improve endothelial function in patients with essential hypertension in different manners, suppression of vascular inflammation, and decrease in blood pressure variability, respectively.

Unilateral axillary lymph node fluorodeoxyglucose uptakes after coronavirus disease 2019 vaccination.

Vaccination against coronavirus disease 2019 (COVID-19) started in early December 2020 worldwide, and healthcare workers in Japan were vaccinated in February 2021. We encountered three patients who underwent 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for cancer screening at our institution, showing FDG uptakes in the axillary lymph nodes, which seemed to be reactive changes. Two of them were males in their 40s and one was a female in her 50s; all of them were healthcare workers. The medical history revealed that they received the Pfizer-BioNTech COVID-19 vaccination twice at their left shoulders before the FDG PET/CT examination. The degree of FDG uptakes were maximum standardized uptake value (SUVmax)=3.2-9.9, SUVmax=5.9-10.3, and SUVmax=2.8-7.9, respectively. They were diagnosed with reactive lymph nodes because of vaccination owing to the absence of abnormal FDG PET/CT findings at other sites. As COVID-19 vaccination becomes more widespread in Japan, radiologists should be aware of these findings to avoid misdiagnosis of FDG uptakes in pathological lymph nodes and to prevent unnecessary additional examinations. Recently, similar FDG PET/CT findings have been reported after receiving the COVID-19 vaccination, and we will report it with a literature review.

Familial paroxysmal kinesigenic dyskinesia with a novel missense variant (Arg2866Trp) in NBEA.

Paroxysmal kinesigenic dyskinesia (PKD) is a movement disorder characterized by episodic involuntary movement attacks triggered by sudden movements, acceleration, or intention to move. We ascertained two Japanese familial cases with PKD. The proband is a 22-year-old woman who had noted sudden brief (<30 s) of involuntary movements provoked by kinesigenic trigger such as starting to run, getting on a train, picking up a telephone receiver and so on at the age of 14. Interictal brain single photon emission computed tomography (SPECT) showed hyperperfusion in the left thalamus. A 46-year-old woman, the mother of the proband was also suffering from brief attacks triggered by starting to run in her high school days. On neurological examination, both showed no abnormality. Whole exome sequencing combined with rigorous filtering revealed two heterozygous nonsynonymous variants (NM_001447: c.8976G > C [p.Gln2992His] in FAT2 and NM_015678: c.8596C > T [p.Arg2866Trp] in NBEA). Real time quantitative PCR analysis of Nbea mRNA levels in the developing rat brain revealed peak at postnatal day 28 and decline at postnatal day 56. This result might match the most common clinical course of PKD from the point of view of the most common age at remission. NBEA has been reported to be responsible for neurodevelopmental disease accompanied by epilepsy. We concluded the variant in NBEA most likely to be responsible for our familial cases of PKD.

Imaging features in patients with SAPHO/CRMO: a pictorial review.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome and chronic recurrent multifocal osteomyelitis (CRMO) have been described as disorders of chronic osteoarthritic inflammation frequently associated with skin manifestations, and SAPHO and CRMO (SAPHO/CRMO) are rare autoinflammatory disorders of unknown etiology. SAPHO tends to occur in adults and CRMO predominantly occurs in children and adolescents. SAPHO/CRMO can affect any skeletal region (e.g., anterior chest wall, spine, or long bones). As SAPHO/CRMO are diagnoses of exclusion, the diagnoses might be difficult if skin manifestations are not clearly evident. However, knowledge of the imaging findings of skeletal disorders is helpful for correcting the diagnosis and avoiding unnecessary invasive procedures, as well as in facilitating early diagnosis and adequate treatment. This pictorial review describes the appearance of increased skeletal uptake for SAPHO/CRMO on bone scintigraphy along with findings from radiography, computed tomography, and magnetic resonance imaging.

Two-hour postload plasma glucose and pigment epithelium-derived factor levels are markers of coronary artery inflammation in type 2 diabetic patients.

BACKGROUND: We have previously found that pioglitazone attenuates inflammation in the left main trunk of coronary artery (LMT), evaluated as target-to-background ratio (TBR) by 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in patients with impaired glucose tolerance or type 2 diabetes. OBJECTIVES: We assessed which clinical variables could predict the change in TBR in the LMT after 4-month add-on therapy with oral hypoglycemic agents (OHAs). METHODS: A total of 38 type 2 diabetic patients with carotid atherosclerosis who had already received OHAs except for pioglitazone was enrolled. At baseline and 4 months after add-on therapy with pioglitazone or glimepiride, all patients underwent 75 g oral glucose tolerance test, blood chemistry analysis, and FDG-PET/CT. RESULTS: Fasting plasma glucose, 30-, 60-, 90-, 120-minutes postload plasma glucose, HbA1c, and LMT-TBR values were significantly decreased by add-on therapy, whereas high-density lipoprotein-cholesterol and adiponectin levels were increased. Increased serum levels of pigment epithelium-derived factor (PEDF), a marker of insulin resistance and non-use of aspirin at baseline could predict the favorable response of LMT-TBR to add-on therapy. Moreover, Δ120-minutes postload plasma glucose and ΔPEDF were independent correlates of ΔLMT-TBR. CONCLUSIONS: Our present study suggests that 120-minutes postload plasma glucose and PEDF values may be markers and potential therapeutic targets of coronary artery inflammation in type 2 diabetic patients. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov . Unique identifier: NCT00722631. New markers for diabetes and CAD is on the horizon! Two-hour postload plasma glucose and pigment epithelium derived factor are markers of coronary artery inflammation in type 2 diabetic patients.

Multimodal imaging of cardiac-calcified amorphous tumor.

Cardiac-calcified amorphous tumor (CAT) is a rare non-neoplastic tumor and its origin and pathogenesis are still unclear. In addition, it is difficult to clinically diagnose as cardiac CAT without pathological findings. We present a case of a 78-year-male diagnosed with cardiac CAT after surgical resection. We could evaluate tumor aspects by multimodal imaging including echocardiography, contrast-enhanced computed tomography (CT), magnetic resonance image, and 18F-fluorodeoxyglucose-positron emission tomography/CT before surgery.

Bilateral cingulate cortices lesions in two autoantibodies directed against MOG (MOG-Ab)-positive patients.

There are no specific radiologic features in MOG-Ab (autoantibodies directed against myelin oligodendrocyte glycoprotein)-associated diseases. We present two MOG-Ab-positive patients with symmetrical lesions in the bilateral cingulate cortex of the frontal and parietal lobes. Those lesions showed hyperperfusion in acute phase and hypoperfusion in chronic phase on brain SPECT. In both patients, steroid therapy was effective in acute phase and for prevention of recurrence. High signal in the bilateral cingulate cortex on MR T2-weighted and FLAIR images might to be one of the unique findings considered MOG-Ab associated diseases.

Marked accumulation of fluorodeoxyglucose and inflammatory cells expressing glucose transporter-3 in immunoglobulin G4-related autoimmune hepatitis.

Immunoglobulin (Ig)G4-related autoimmune hepatitis (AIH) is a recently proposed subtype that responds well to steroid treatment; however, its pathogenesis remains unclear. We report here a 65-year-old Japanese woman with skin itching and lip swelling. She had liver injury with jaundice, which persisted despite stopping anti-allergic agents. Blood chemistry revealed highly elevated serum IgG and IgG4 (535 mg/dL) levels, and positive anti-nuclear antibody. The diagnosis of AIH was based on liver biopsy. Notably, the IgG4+ /IgG+ cell ratio was 85%. On fluorodeoxyglucose (FDG) positron emission tomography/computed tomography, robust signal intensity was found in the liver, and in enlarged lymph nodes and salivary glands with confirmed IgG4+ cell infiltration. Immunofluorescence analysis of the liver biopsy specimen indicated clear expression of glucose transporter-3 (Glut-3) in IgG4+ inflammatory cells infiltrating into the portal area. This is the first report of simultaneous strong accumulation of FDG and Glut-3 expression in IgG4-related AIH, which might aid in elucidating the pathogenesis of this disease.

Clinical significance of patterns of increased [18F]-FDG uptake in the thyroid gland: a pictorial review.

In the diagnosis and staging of oncologic patients, [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) is well recognized as an important functional imaging modality. FDG-PET also has been used for cancer screening in healthy individuals. In general, the normal thyroid gland shows absent or low uptake on FDG-PET, which is often identified as an incidental finding on PET. Today, thyroid FDG uptake can be seen in three patterns: diffuse; focal; and diffuse-plus-focal. Diffuse thyroid uptake is mainly considered an indicator of chronic thyroiditis. Focal thyroid uptake has been associated with malignancy (range 25-50%). Diffuse-plus-focal uptake is not well recognized and might also indicate a risk of malignancy. Understanding the patterns of thyroid FDG uptake is thus important for nuclear medicine physicians or radiologists when giving recommendations to the referring physician. In this pictorial review, we show the clinical significance of different patterns of thyroid uptake on FDG-PET [PET/computed tomography (CT)], including ultrasonography (US) findings.

Clinical spectrum and diagnostic pitfalls of multiple abnormal uptakes on bone scintigraphy.

Bone scintigraphy with technetium-99m (99mTc)-labeled diphosphonates is one of the most frequently performed radionuclide procedures. Accumulation of 99mTc-labeled diphosphonate is well recognized to reflect conditions of accelerated bone turnover and metabolism. Therefore, it is a functional imaging modality for detecting metastatic bone tumors, metabolic bone disease, traumatic injury, and inflammation. This pictorial essay describes the possible patterns of distribution of abnormal uptake for differential diagnosis of metastatic bone tumor, as well as the diagnostic pitfalls of bone scintigraphy.