scholarly journals Τhe Greek Variant in APP Gene: The Phenotypic Spectrum of APP Mutations

2021 ◽  
Vol 22 (22) ◽  
pp. 12355
Author(s):  
Stefania Kalampokini ◽  
Despoina Georgouli ◽  
Eleni Patrikiou ◽  
Antonios Provatas ◽  
Varvara Valotassiou ◽  
...  

Mutations in the gene encoding amyloid precursor protein (APP) cause autosomal dominant inherited Alzheimer’s disease (AD). We present a case of a 68-year-old female who presented with epileptic seizures, neuropsychiatric symptoms and progressive memory decline and was found to carry a novel APP variant, c.2062T>G pLeu688Val. A comprehensive literature review of all reported cases of AD due to APP mutations was performed in PubMed and Web of Science databases. We reviewed 98 studies with a total of 385 cases. The mean age of disease onset was 51.3 ± 8.3 (31–80 years). Mutations were most often located in exons 17 (80.8%) and 16 (12.2%). The most common symptoms were dementia, visuospatial symptoms, aphasia, epilepsy and psychiatric symptoms. Mutations in the β-amyloid region, and specifically exon 17, were associated with high pathogenicity and a younger age of disease onset. We describe the second reported APP mutation in the Greek population. APP mutations may act variably on disease expression and their phenotype is heterogeneous.

Lupus ◽  
2021 ◽  
pp. 096120332110339
Author(s):  
Sirong Piao ◽  
Rong Wang ◽  
Haihong Qin ◽  
Bin Hu ◽  
Juan Du ◽  
...  

Purpose To explore the alterations of spontaneous neuronal activity using amplitude of low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuation (fALFF), and regional homogeneity (ReHo) in non-NPSLE patients and their relationship with the anxiety and depression statuses. Methods Twenty-three non-NPSLE patients and 28 healthy controls were enrolled in this study. Resting-state functional magnetic resonance imaging was firstly analyzed by ALFF, fALFF, and ReHo. The relationships between ALFF/fALFF/ReHo values of abnormal regions and anxiety/depression rating scales, including Self-Rating Anxiety (SAS) and Self-Rating Depression (SDS), were also analyzed. Results Compared with HC, non-NPSLE had decreased ALFF values in the bilateral postcentral gyrus, while increased ALFF values in the bilateral inferior temporal gyrus, left putamen, and bilateral precuneus. Non-NPSLE showed reduced fALFF values in the left lingual gyrus, left middle occipital gyrus, right postcentral gyrus, and left superior parietal gyrus, while increased fALFF values were in the left inferior temporal gyrus, right hippocampus, bilateral precuneus, and bilateral superior frontal gyrus. Reduced ReHo values were in the bilateral postcentral gyrus and higher ReHo values were in the left inferior temporal gyrus, left putamen, and bilateral superior frontal gyrus. In the non-NPSLE group, the mean ALFF values of bilateral precuneus were positively correlated with the SAS rating scales (R = 0.5519, p = 0.0176); either were the mean ALFF values of right inferior temporal gyrus and SAS rating scales (R = 0.5380, p = 0.0213). The mean fALFF values of left inferior temporal gyrus were positively correlated with SAS rating scales (R = 0.5700, p = 0.0135). And the mean ReHo values of left putamen were positively correlated with SDS (R = 0.5477, p = 0.0186). Conclusion Non-NPSLE exhibited abnormal spontaneous neural activity and coherence in several brain regions mainly associated with cognitive and emotional functions. The ALFF values of bilateral PCUN, the right ITG, the fALFF values of left ITG, and the ReHo values of left PUT may be complementary biomarkers for assessing the psychiatric symptoms.


Neurology ◽  
2020 ◽  
Vol 94 (13) ◽  
pp. e1344-e1352 ◽  
Author(s):  
Han Soo Yoo ◽  
Sangwon Lee ◽  
Seok Jong Chung ◽  
Yang Hyun Lee ◽  
Byoung Seok Ye ◽  
...  

ObjectiveTo investigate the relationship between β-amyloid (Aβ) deposition and striatal dopamine depletion, cognitive functions, and neuropsychiatric symptoms in dementia with Lewy bodies (DLB).MethodsWe consecutively recruited 51 patients with DLB who had undergone a neuropsychological test, Neuropsychiatric Inventory assessment, brain MRI, N-(3-[18F]fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) PET, and 18F-florbetaben PET within 6 months. The patients were divided into Aβ-negative (DLB-Aβ−, n = 20) and Aβ-positive (DLB-Aβ+, n = 31) groups according to the brain amyloid plaque load score. We performed comparative analyses of dopamine transporter (DAT) activity, neuropsychological profile, and neuropsychiatric symptoms between the 2 groups.ResultsCompared to the DLB-Aβ− group, the DLB-Aβ+ group had a younger age at diagnosis (p = 0.017), poorer performance in attention (p = 0.028) and visuospatial (p = 0.006) functions, and higher proportion of anxiety (p = 0.006) and total neuropsychiatric burden (p = 0.013). Those in the DLB-Aβ+ group also had lower DAT activity in the anterior putamen (p = 0.015) and ventral striatum (p = 0.006) regardless of age, sex, and years of education. In addition, lower DAT activity in the ventral striatum was significantly associated with anxiety and total neuropsychiatric burden in DLB.ConclusionsThis study demonstrated that Aβ deposition in DLB is associated with diagnosis at a younger age, higher cognitive and neuropsychiatric burden, and decreased DAT activity, suggesting that evaluation of clinical features and DAT activity can predict the presence of Aβ in DLB.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1285.2-1285
Author(s):  
S. Bouden ◽  
L. Kharrat ◽  
A. Ben Tekaya ◽  
O. Saidane ◽  
R. Tekaya ◽  
...  

Background:The deleterious effect of smoking on spondyloarthritis has been studied for several decades. Indeed, smoking increases inflammation and disease activity, hence, promotes bone damage.Objectives:The aim of our study was to evaluate the clinical, biological and radiological impact of smoking on axial spondyloarthritis (axSpA).Methods:We conducted a retrospective study including patients meeting the Assessment of SpondyloArthritis international Society (ASAS) criteria between 2000 and 2020.The following parameters were collected: age, smoking, ASDAS, BASDAI, and BASFI. We also measured inflammatory biomarkers (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)).Results:We included 138 patients. Sixty-eight per cent of them were males. The mean age was 45.73 ± 12.66 years. The mean age at the disease onset was 28.89 ± 12.54 years. The mean CRP was 33.38 ± 39.65 mg/dL. The mean BASDAI and ASDAS-CRP were 4.21 ±2.23 and 3.06 ± 1.26, respectively. The mean BASFI was 4.77 ± 2.58.Fifty-one of our patients were smokers (37%). They were 48 men and 3 women. The mean pack-year was 45 ± 17.15.Smokers had a significantly younger age of the disease onset (25.21 ± 11.37 versus 31.96 ± 12.67, p=0.009).Moreover, patients who smoke Tabaco had developed significantly more ankylosis compared to patients who don’t (p=0.026).Osteoporosis was also more frequent in smoking patients (p=0.032).However, no association was found between smoking and ESR, CRP, ASDAS-CRP, BASDAI and BASFI.Conclusion:Our results reveal that smoking can be responsible of a younger axSpA onset, and can lead to more severe structural damages regardless the disease activity. This highlights the importance of smoking cessation in preventing early bone damage in axSpA.Disclosure of Interests:None declared.


2021 ◽  
Vol 8 (4) ◽  
pp. e1019
Author(s):  
Gerda Ricken ◽  
Tobias Zrzavy ◽  
Stefan Macher ◽  
Patrick Altmann ◽  
Johannes Troger ◽  
...  

ObjectiveTo report an unusual clinical phenotype of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis and describe associated neuropathologic findings.MethodsWe retrospectively investigated 3 AMPAR encephalitis patients with autoimmune global hippocampal amnesia using comprehensive cognitive and neuropsychologic assessment, antibody testing by in-house tissue-based and cell-based assays, and neuropathologic analysis of brain autopsy tissue including histology and immunohistochemistry.ResultsThree patients presented with acute-to-subacute global amnesia without affection of cognitive performance, attention, concentration, or verbal function. None of the patients had epileptic seizures, change of behavior, personality changes, or psychiatric symptoms. The MRI was normal in 1 patient and showed increased fluid-attenuated inversion recovery/T2 signal in the hippocampus in the other 2 patients. Two patients showed complete remission after immunotherapy. The one patient who did not improve had an underlying adenocarcinoma of the lung and died 3.5 months after disease onset because of tumor progression. Neuropathologic analysis of the brain autopsy revealed unilateral hippocampal sclerosis accompanied by mild inflammatory infiltrates, predominantly composed of T lymphocytes, and decrease of AMPAR immunoreactivity.ConclusionAMPAR antibodies usually associate with limbic encephalitis but may also present with immune responsive, acute-to-subacute, isolated hippocampal dysfunction without overt inflammatory CSF or MRI changes.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Michał Terpiłowski ◽  
Barbara Terpiłowska ◽  
Anna Orzeł ◽  
Dominika Szlichta ◽  
Marcin Łata ◽  
...  

Abstract Introduction: Susac syndrome (SuS) is a rare immune-mediated disease caused by occlusions of microvessels in the brain, retina and inner ear. It is characterized by the clinical triad of encephalopathy, visual disturbances and hearing loss. The diagnosis of SuS is based mainly on the clinical symptoms and the supporting tests in which characteristic changes occur in the MRI. Case report: Here, we present a case of a patient with possible SuS with psychiatric symptoms. A 31-year-old woman was admitted to the Department of Psychiatry due to deteriorating mental health for several weeks manifested as a negative mood and suicidal thoughts. During hospitalization, a neurological consultation was conducted, in which the patient was identified as conscious, psychomotor sluggish, with impaired verbal contact and persistent hearing and vision impairment. Cross-sectional assessment of cognitive functions revealed that the patient had a generalized syndrome of neuropsychological deficits, which confirms the diagnosis of dementia. Discussion: This case summary provides an example of a woman diagnosed with SuS manifested as a cognitive impairment with associated vision and hearing deterioration. It is worth emphasizing the fact that such presentation of the triad of at disease onset is rare. The characteristics of the organic changes in the brain described in the MRI probably explain the symptoms described in that case. The prognosis of SuS depends on early diagnosis and treatment. Conclusions: A diagnosis of SuS should always be considered in the presence of nonspecific neuropsychiatric symptoms and progressive multifocal neurological symptoms, hearing loss, and visual impairment. An important fact is that the typical triad of SuS symptoms in most cases does not occur simultaneously, which makes the diagnostic process very difficult and may lead to misdiagnosis.


2020 ◽  
Vol 26 (1) ◽  
pp. 53-59 ◽  
Author(s):  
Jennifer M. Strahle ◽  
Rukayat Taiwo ◽  
Christine Averill ◽  
James Torner ◽  
Jordan I. Gewirtz ◽  
...  

OBJECTIVEIn patients with Chiari malformation type I (CM-I) and a syrinx who also have scoliosis, clinical and radiological predictors of curve regression after posterior fossa decompression are not well known. Prior reports indicate that age younger than 10 years and a curve magnitude < 35° are favorable predictors of curve regression following surgery. The aim of this study was to determine baseline radiological factors, including craniocervical junction alignment, that might predict curve stability or improvement after posterior fossa decompression.METHODSA large multicenter retrospective and prospective registry of pediatric patients with CM-I (tonsils ≥ 5 mm below the foramen magnum) and a syrinx (≥ 3 mm in width) was reviewed for clinical and radiological characteristics of CM-I, syrinx, and scoliosis (coronal curve ≥ 10°) in patients who underwent posterior fossa decompression and who also had follow-up imaging.RESULTSOf 825 patients with CM-I and a syrinx, 251 (30.4%) were noted to have scoliosis present at the time of diagnosis. Forty-one (16.3%) of these patients underwent posterior fossa decompression and had follow-up imaging to assess for scoliosis. Twenty-three patients (56%) were female, the mean age at time of CM-I decompression was 10.0 years, and the mean follow-up duration was 1.3 years. Nine patients (22%) had stable curves, 16 (39%) showed improvement (> 5°), and 16 (39%) displayed curve progression (> 5°) during the follow-up period. Younger age at the time of decompression was associated with improvement in curve magnitude; for those with curves of ≤ 35°, 17% of patients younger than 10 years of age had curve progression compared with 64% of those 10 years of age or older (p = 0.008). There was no difference by age for those with curves > 35°. Tonsil position, baseline syrinx dimensions, and change in syrinx size were not associated with the change in curve magnitude. There was no difference in progression after surgery in patients who were also treated with a brace compared to those who were not treated with a brace for scoliosis.CONCLUSIONSIn this cohort of patients with CM-I, a syrinx, and scoliosis, younger age at the time of decompression was associated with improvement in curve magnitude following surgery, especially in patients younger than 10 years of age with curves of ≤ 35°. Baseline tonsil position, syrinx dimensions, frontooccipital horn ratio, and craniocervical junction morphology were not associated with changes in curve magnitude after surgery.


2020 ◽  
Vol 16 (3) ◽  
pp. 241-247
Author(s):  
Atifete Ramosaj-Morina ◽  
Alije Keka-Sylaj ◽  
Arbana Baloku Zejnullahu ◽  
Lidvana Spahiu ◽  
Virgjina Hasbahta ◽  
...  

Background: Celiac disease is an immune-mediated disorder characterized by variable clinical manifestations, specific antibodies, HLA-DQ2/DQ8 haplotypes, and enteropathy. Objectives: The aim of this study was to present the clinical spectrum and patterns of celiac disease in Kosovar Albanian children. Methods: A cross-sectional retrospective study was performed with Albanian children aged 0-18 years, treated for celiac disease in the Pediatric Clinic, University Clinical Center of Kosovo from 2005 to 2016. Results: During the study period, 63 children were treated for celiac disease. The mean age at diagnosis was 5.5 years (SD ± 3.31). The mean age at celiac disease onset was 3.3 years (SD ± 2.02), while the mean delay from the first symptoms indicative of celiac disease to diagnosis was 2.2 years (SD ± 2.09). More than 70% of the patients were diagnosed in the first 7 years of life, mainly presented with gastrointestinal symptoms, while primary school children and adolescents mostly showed atypical symptoms (p<0.001). The classical form of celiac disease occurred in 78% of the cases. Sixty (95%) patients carried HLA-DQ2.5, DQ2.2 and/or HLA-DQ8 heterodimers, and only three of them tested negative. Conclusions: Kosovo, as the majority of developing countries, is still facing the classical form of celiac disease as the dominant mode of presentation; as a result, most children with other forms of the celiac disease remain undiagnosed. : Physicians should be aware of the wide range of clinical presentations and utilize low testing thresholds in order to prevent potential long-term problems associated with untreated celiac disease.


Lupus ◽  
2021 ◽  
pp. 096120332110050
Author(s):  
Rory C Monahan ◽  
Liesbeth JJ Beaart-van de Voorde ◽  
Jeroen Eikenboom ◽  
Rolf Fronczek ◽  
Margreet Kloppenburg ◽  
...  

Introduction We aimed to investigate risk factors for fatigue in patients with systemic lupus erythematosus (SLE) and neuropsychiatric symptoms in order to identify potential interventional strategies. Methods Patients visiting the neuropsychiatric SLE (NPSLE) clinic of the Leiden University Medical Center between 2007–2019 were included. In a multidisciplinary consensus meeting, SLE patients were classified as having neuropsychiatric symptoms of inflammatory origin (inflammatory phenotype) or other origin (non-inflammatory phenotype). Fatigue was assessed with the SF-36 vitality domain (VT) since 2007 and the multidimensional fatigue inventory (MFI) and visual analogue scale (VAS) since 2011. Patients with a score on the SF-36 VT ≥1 standard deviation (SD) away from the mean of age-related controls of the general population were classified as fatigued; patients ≥2 SD away were classified as extremely fatigued. Disease activity was measured using the SLE disease activity index-2000. The influence of the presence of an inflammatory phenotype, disease activity and symptoms of depression and anxiety as measured by the hospital anxiety and depression scale (HADS) was analyzed using multiple regression analyses corrected for age, sex and education. Results 348 out of 371 eligible patients filled in questionnaires and were included in this study . The majority was female (87%) and the mean age was 43 ± 14 years. 72 patients (21%) had neuropsychiatric symptoms of an inflammatory origin. Fatigue was present in 78% of all patients and extreme fatigue was present in 50% of patients with an inflammatory phenotype vs 46% in the non-inflammatory phenotype. Fatigue was similar in patients with an inflammatory phenotype compared to patients with a non-inflammatory phenotype on the SF-36 VT (β: 0.8 (95% CI −4.8; 6.1) and there was less fatigue in patients with an inflammatory phenotype on the MFI and VAS (β: −3.7 (95% CI: −6.9; −0.5) and β: −1.0 (95% CI −1.6; −0.3)). There was no association between disease activity and fatigue, but symptoms of anxiety and depression (HADS) associated strongly with all fatigue measurements. Conclusion This study suggests that intervention strategies to target fatigue in (NP)SLE patients may need to focus on symptoms of anxiety and depression rather than immunosuppressive treatment.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1537.1-1537
Author(s):  
R. Goloeva ◽  
Z. Alekberova

Background:Behcet’s disease (BD) is systemic vasculitis, which affects all types and sizes of vessels. Increased carotid intima-media thickness (IMT) is parameter associated with subclinical atherosclerosis.Objectives:To determine the prevalence of atherosclerosis in pts with BD.Methods:95 BD pts were evaluated and 45 healthy controls matched for age and gender.IMT was assessed by high-resolution B-mode ultrasonography. Serum concentration of high-sensitivity C-reactive protein (hs CRP) was measured by immunonephelometric assay (BN-100 Analyzer; Dade Behring). Lipid profile evaluation included total cholesterol, TGs, HDL, LDL and atherogenic index.Results:The male-to-female ratio was 3,7:1, the mean age of pts was 29.7 (23-35) yrs, the mean age at the disease onset - 19,9 (14-25) yrs, the mean disease duration - 9,6 (4-15) yrs.Conclusion:Coronary atherosclerosis in BD pts was lower than what we expected. The thinning IMT may be one of the risk factors for aneurysm formation in pts with BD.Disclosure of Interests:None declared


2021 ◽  
pp. 112067212110307
Author(s):  
Soner Guven

Purpose: To compare the prevalence, magnitude and type of corneal astigmatism between Turkish individuals and Syrian refugees. Material and methods: Data of patients scheduled for cataract surgery between January 2019 and 2020 were reviewed. The patients were randomly stratified according to their ethnicity (Turkish individuals or Syrian refugees). Keratometry was performed with the keratometer of IOLMaster 500. Quantitative analysis was performed using the power vector method (J0 and J45). The association between age and astigmatism in the two groups was explored. Results: The study included 4085 eyes of 2049 patients (3962 eyes of Turkish individuals and 123 eyes of Syrian refugees). The mean magnitude of corneal astigmatism, J0, J45 and prevalence of against the rule (ATR) astigmatism and with the rule (WTR) astigmatism were 1.01 D, 0.06, 0.01 D, 37.6% and 43.7% in Turkish individuals and 1.13 D, −0.02, 0.07 D, 46.3% and 37.4% in Syrian refugees, respectively. There were no significant differences according to age, sex, right/left eyes, corneal astigmatism magnitude, keratometric values, J0 and J45 ( p > 0.05) between the two groups. Below 40 years of age, the mean corneal astigmatism magnitude in Syrian refugees was significantly higher than that in Turkish individuals ( p = 0.037). At all ages, ATR astigmatism prevalence was higher in Syrian refugees than in Turkish individuals. ATR astigmatic shift began at a younger age in Syrian refugees ( p = 0.037). Age- and sex-adjusted analysis showed that J0 was significantly lower in Syrian refugees than in Turkish individuals ( p = 0.013). Conclusion: The prevalence and magnitude of ATR astigmatism were higher and onset earlier in Syrian refugees than in Turkish individuals.


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