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Background: MAPT variants are a known cause of frontotemporal dementia and Parkinsonian syndrome, of which progressive supranuclear palsy syndrome (PSP) is a rare manifestation. Objective: To report a novel MAPT variant in a PSP pedigree with autosomal dominant inheritance pattern, and to produce a literature review of PSP patients with MAPT variants. Methods: A comprehensive clinical, genetic, and molecular neuroimaging investigation was conducted on a 61 years-old female proband diagnosed with PSP. We also collected the clinical presentation data and history of the patient's pedigree, and performed further genetic analysis of 4 relatives, from two generations, with and without symptoms. Results: The proband exhibited typical clinical manifestation of PSP. A cranial MRI revealed midbrain atrophy, and an FDG-PET scan suggested hypo-metabolic changes in caudate nucleus, left prefrontal lobe, both temporal poles, and midbrain. 18F-florzolo-tau-PET revealed tau-protein deposits in the thalamus and brainstem bilaterally. A gene test by whole-exome sequencing identified a novel MAPT variant [NM_005910.6, exon 11, c.1024G > A (p.E342K)], and the same variant was also identified in one affected relative and one asymptomatic relative, a probable pre-symptomatic carrier. Conclusion: The PSP pedigree caused by the novel MAPT (E342K) variant, expanded the mutational spectrum of MAPT. [ABSTRACT FROM AUTHOR]

Objective: To describe clinical phenotypes and prognosis of neurological autoimmunity related to glutamic acid decarboxylase 65 (GAD65) antibodies in China. Method: In this retrospective observational study from Peking Union Medical College Hospital, we identified patients with neurological disorders related to GAD65 antibodies (cell-based assay) from May 2015 to September 2021. Clinical manifestations, immunotherapy responsiveness, and outcomes were collected after obtaining informed consent from all patients. Results: Fifty-five patients were included: 40 (72.73%) were women and initial neurological symptoms developed at 42(34-55) years of age. The median time to the nadir of the disease was 5 months (range from 1 day to 48 months). The clinical syndromes included limbic encephalitis (LE) or epilepsy (Ep) (n = 34, 61.82%), stiff-person syndromes (SPS) (n = 18, 32.73%), autoimmune cerebellar ataxia (ACA) (n = 11, 20%), and overlap syndrome in eight (14.55%) patients. Thirty-two (58.2%) patients had comorbidities of other autoimmune diseases, including Hashimoto thyroiditis (n = 17, 53.13%), T1DM (n = 11, 34.78%), vitiligo (n = 6, 18.75%), and others (n=5, 15.63%). Two (3.64%) patients had tumors, including thymoma and small cell lung cancer. Fifty-one (92.7%) patients received first-line immunotherapy (glucocorticoids and/or IV immunoglobulin), and 4 (7.3%) received second-line immunotherapy (rituximab). Long-term immunotherapy (mycophenolate mofetil) was administered to 23 (41.8%) patients. At the median time of 15 months (IQR 6--33.75 month, range 3--96 month) of follow-up, the patients' median modified Rankin Score (mRS) had declined from 2 to 1. Thirty-eight (70.4%) patients experienced clinical improvement (mRS declined ≥1), 47 (87%) had favorable clinical outcomes (mRS ≤2), and nine were symptom-free (16.7%). The sustained response to immunotherapy ranged from 7/15 (63.63%) in ACA patients and 22/34 (64.7%) in LE/Ep patients to 14/17 (82.35%) in SPS patients. Conclusions: LE/Ep was the most common neurological phenotype of GAD65 antibody neurological autoimmunity in our cohort. Most patients had comorbidities of other autoimmune diseases, but underlying tumors were rare. Most patients responded to immunotherapy. However, the long-term prognosis varied among different clinical phenotypes. [ABSTRACT FROM AUTHOR]

This work evaluated the use of the positron emission tomography (PET)/computed tomography (CT) technique to assess the early therapeutic response and predict the prognosis of patients with radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) who underwent apatinib therapy. Standardised uptake value (SUV), metabolic tumour volume (MTV) and total lesion glycolysis (TLG), derived from 18F-FDG PET/CT and SUV from 68Ga-NOTA-PRGD2 PET/CT were evaluated. Tumour response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Sixteen of 20 patients achieved partial response (PR) and four of 20 had stable disease (SD) after apatinib therapy. Six progression-free survival (PFS) events occurred. A strong correlation was observed between the best change in the sum of the longest diameters of target lesions (ΔCT%) and 18F-FDG PET/CT indices after the completion of the frst treatment cycle (ΔMTV% (P = 0.0019), ΔTLG% (P = 0.0021) and ΔSUVmax% (P = 0.0443)). A signifcant difference in PFS was observed between patients with ΔMTV% <-45% and ≥-45% (P = 0.0019) and between patients with ΔTLG% <-80% and ≥-80% (P = 0.0065). Ten of 11 patients presented a decrease in SUVmax on 68Ga-NOTA-PRGD2 PET/CT after two cycles of apatinib therapy and showed PR, whereas one patient presenting an increase in SUVmax only showed SD as the best response. When a cut-off value of the target/background ratio at -20% was used, two PFS curves showed a signifcant difference (P = 0.0016). Hence, early assessment by 18F-FDG and 68Ga-NOTA-PRGD2 PET/CT was effective in the prediction and evaluation of RAIR-DTC treated with apatinib. [ABSTRACT FROM AUTHOR]

The apolipoprotein E (APOE) ɛ4 allele is the strongest genetic risk factor for Alzheimer's disease (AD). This study aimed to investigate abnormality of white matter integrity and its relationship to cognitive impairments in Chinese non-demented elderly with and without the ɛ4 allele. We assessed cognitive differences using a series of neuropsychological tests and assessed white matter integrity using tract-based spatial statistics to measure mean diffusivity and fractional anisotropy. We determined that there were no statistically significant group differences in any neuropsychological measures. However, APOEɛ4 carriers without cognitive decline exhibited widespread disruption of the white matter tracts in several areas, including the cingulum, fornix, corpus callosum, and corona radiate. Furthermore, a correlation analysis in ɛ4 carriers indicated that disruption of the right fornix stria terminalis and the genu of the corpus callosum were positively associated with cognitive impairment, including memory, executive function, spatial processing, attention, and language. The present study reveals the deleterious effects of the ɛ4 allele on white matter, and this damage may potentially serve as a biomarker in preclinical investigations. Our promising results encourage further investigation using a multidimensional longitudinal approach with larger samples. [ABSTRACT FROM AUTHOR]