Causal association between atopic dermatitis and Parkinson's disease: A bidirectional Mendelian randomization study.

BACKGROUND: Atopic dermatitis is one of the most common skin disorders. Evidence has suggested an association between skin disorders, such as atopic dermatitis, and Parkinson's disease (PD). However, whether atopic dermatitis has a causal effect on PD remains unknown. METHODS: The study aimed to determine whether their association between atopic dermatitis and PD is causal, using a bidirectional two-sample Mendelian randomization method. Genetic variants from the public genome-wide association studies for atopic dermatitis (n = 10788 cases and 30047 controls) were selected to evaluate their causal effects on the risk of PD (33,674 cases and 449,056 controls). The inverse variance weighted (IVW) method was used as the primary analysis. RESULTS: The IVW results indicated that atopic dermatitis was associated with decreased risk of PD {fixed effects: odds ratio [OR] [95% confidence interval (CI)]: .905 [.832-.986], p = .022; OR [95% CI]: .905 [.827-.991], p = .032}. However, we failed to detect the causal effects of PD on risk of atopic dermatitis in the reverse causation analysis. CONCLUSION: This study indicated causal association of genetically proxied atopic dermatitis with the risk of PD. Future studies are warranted to explore the underlying mechanism and investigate the targeting effect of atopic dermatitis on PD.

Unconjugated bilirubin is correlated with the severeness and neurodevelopmental outcomes in neonatal hypoxic-ischemic encephalopathy.

Unconjugated bilirubin (UB) levels during the first week after birth are related to outcomes in neonatal hypoxic-ischemic encephalopathy (HIE). Clinical Sarnat staging of HIE, brain magnetic resonance imaging (MRI), hearing outcomes, and neurodevelopmental outcomes ≥ 1 year were used to correlate UB in 82 HIE patients. The initial UB level was significantly correlated with lactic acid levels. The peak UB was higher (p < 0.001) in stage I (10.13 ± 4.03 mg/dL, n = 34) than in stages II and III (6.11 ± 2.88 mg/dL, n = 48). Among the 48 patients receiving hypothermia treatment, a higher peak UB was significantly (p < 0.001) correlated with unremarkable brain MRI scans and unremarkable neurodevelopmental outcomes at age ≥ 1 year. The peak UB were higher (P = 0.015) in patients free of seizures until 1 year of age (6.63 ± 2.91 mg/dL) than in patients with seizures (4.17 ± 1.77 mg/dL). Regarding hearing outcomes, there were no significant differences between patients with and without hearing loss. The UB level in the first week after birth is an important biomarker for clinical staging, MRI findings, seizures after discharge before 1 year of age, and neurodevelopmental outcomes at ≥ 1 year of age.

[Electroencephalogram Features of Anti-N-Methyl-D-Aspartate Receptor Encephalitis and Their Value for Clinical Assessment].

Objective: To analyze the electroencephalogram (EEG) features of anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) and to study the clinical assessment value of the degree of EEG background slowing and the presence of δ brush. Methods: We enrolled 52 patients with anti-NMDARE and collected their clinical data, including age, sex, form of disease onset, status of tumor comorbidity, auxiliary examination findings (cerebrospinal fluid [CSF] anti-methyl-D-aspartate receptor antibody titers, magnetic resonance imaging [MRI] reports, and EEG results), treatment status, and follow-up after discharge. The degree of EEG background abnormality and the presence of δ brush in the EEG of patients with different clinical features were analyzed. Results: Among the 52 patients, 7 (14%) had normal EEG, and 45 (87%), abnormal EEG, including 25 (48%) with mild abnormalities, 11 (21%) with moderate abnormalities, and 9 (17%) with severe abnormalities. δ brush was seen in 6 (12%) patients. At the time of EEG, 32 (62%) patients were in the mild condition group and 20 (38%) patients were in the severe condition group. After 1 year of follow-up, there were 45 (86%) patients in the good prognosis group and 7 (14%) patients in the poor prognosis group. The exacerbation of EEG background abnormalities and the presence of δ brush were indications for an increase in the proportion of patients who were in severe condition, who needed ICU admission, and who had poor prognosis ( P<0.01). The worse the EEG background abnormalities, the higher the proportion of CSF antibody titers>1∶10 ( P=0.035), and the higher the proportion of patients initiating second-line immunotherapy ( P=0.008). The δ brush was seen a higher proportion in patients with comorbid tumors ( P=0.012). The probability of δ brush presence was higher in the first-time diagnosis cases than that in recurrent cases ( P=0.023). Conclusions: The degree of EEG slowing and the presence of δ brush have shown consistent performance in assessing patients' condition and predicting prognosis. The slower the EEG, the more severe the disease, and the worse the prognosis. The presence of δ brush indicates severe disease and poor prognosis. EEG slowing is correlated with the immune status of patients with anti-NMDARE. The slower the EEG, the more severe the immune abnormalities. In clinical practice, patient EEG should be under dynamic monitoring in order to evaluate the effect of immunotherapy. If EEG slowing is not improved, enhanced immunotherapy should be considered as early as possible. The δ brush is seen at a higher proportion in patients with comorbid tumors. Therefore, active efforts should be made to screen for tumors when δ brush is present.

The association between cerebrospinal ferritin and soluble triggering receptor expressed on myeloid cells 2 along Alzheimer's continuum.

Brain iron accumulation, which is indicated in the cerebrospinal fluid (CSF) ferritin, is associated with the development of Alzheimer's Disease (AD). Studies have indicated that iron deposition might participate in Alzheimer's pathology through the induction of microglial activation. A soluble triggering receptor expressed on myeloid cells 2 (sTrem2) in CSF is increasingly recognized as a reliable indicator for microglia activity in the brain and participates in the development of neuroinflammation. However, the association between CSF ferritin and sTrem2 under the AD continuum has not been well-established. We enrolled individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Participants were classified into healthy controls (HC, n = 46) and AD continuum (n = 105) in the combined strata of Amyloid/Tau/Neurodegeneration (ATN) mode and Clinical Dementia Rating (CDR) criteria. The associations between CSF ferritin (indicating iron burden) and sTrem2, as well as AD pathology, which is reflected by Aß42, t-tau, and p-tau in CSF, were explored. CSF ferritin was significantly associated with sTrem2 among all participants (ß = 0.517, P < 0.001, FDR < 0.001), HC (ß = 0.749, P = 0.006, FDR = 0.010), and AD continuum (ß = 0.488, P < 0.001, FDR < 0.001), respectively. However, ferritin predicted the accelerated sTrem2 level in those with high ferritin (ß = 0.549, P = 0.036, FDR = 0.045). In conclusion, CSF ferritin serves as a potential biomarker of Trem2-indicated microglia function.

Perivascular Space Predicts Brain Hypometabolism of Individuals with Underlying Amyloid Pathology.

BACKGROUND: Reduced signal on fluorodeoxyglucose-positron emission tomography (FDG-PET) is a valid proxy for neurodegeneration in Alzheimer's disease (AD). Perivascular space (PVS) is believed to be associated with AD pathology and cognitive decline. OBJECTIVE: This study aimed to investigate the associations of PVS with FDG-PET and cognitive performance based on the burden of amyloid pathology. METHODS: We used magnetic resonance imaging (MRI) data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). MRI-visible PVS in basal ganglia (BG) and centrum semi-oval (CSO) were visually classified as: none/mild, moderate or frequent/severe. The association of PVS with brain FDG-PET was explored based on the burden of amyloid pathology, where a cerebrospinal fluid (CSF) t-tau/Aß42 with the ratio≥0.27 was defined as high amyloid pathology. Moreover, the relationships between PVS and cognitive performance variables (ADNI-MEM and ADNI-EF) were studied. RESULTS: For participants with higher tau/Aß42 ratio, CSO-PVS severity was independently associated with lower FDG-PET. There were significant interaction effects between moderate or frequent/severe CSO-PVS and time on FDG decline in people with high amyloid pathology. The interaction between CSO-PVS and time (follow-up) was consistently associated with ADNI-MEM and ADNI-EF decline in individuals with high amyloid pathology. CONCLUSION: The study established the differential utility of PVS in BG and CSO for predicting brain metabolism. These findings suggest that CSO-PVS serves as a contributing factor to brain metabolism and cognitive decline associated with amyloid pathology.

The associations between plasma soluble Trem1 and neurological diseases: a Mendelian randomization study.

BACKGROUND: Triggering receptor expressed on myeloid cell 1 (Trem1) is an important regulator of cellular inflammatory responses. Neuroinflammation is a common thread across various neurological diseases. Soluble Trem1 (sTrem1) in plasma is associated with the development of central nervous system disorders. However, the extent of any causative effects of plasma sTrem1 on the risk of these disorders is still unclear. METHOD: Genetic variants for plasma sTrem1 levels were selected as instrumental variables. Summary-level statistics of neurological disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), epilepsy, cerebrovascular diseases, and migraine were collected from genome-wide association studies (GWASs). Whether plasma sTrem1 was causally associated with neurological disorders was assessed using a two-sample Mendelian randomization (MR) analysis, with false discovery rate (FDR)-adjusted methods applied. RESULTS: We inferred suggestive association of higher plasma sTrem1 with the risk of AD (odds ratio [OR] per one standard deviation [SD] increase = 1.064, 95% CI 1.012-1.119, P = 0.014, PFDR = 0.056). Moreover, there was significant association between plasma sTrem1 level and the risk of epilepsy (OR per one SD increase = 1.044, 95% CI 1.016-1.072, P = 0.002, PFDR = 0.032), with a modest statistical power of 41%. Null associations were found for plasma sTrem1 with other neurological diseases and their subtypes. CONCLUSIONS: Taken together, this study indicates suggestive association between plasma sTrem1 and AD. Moreover, higher plasma sTrem1 was associated with the increased risk of epilepsy. The findings support the hypothesis that sTrem1 may be a vital element on the causal pathway to AD and epilepsy.

Segmental zoster paresis of unilateral upper extremity: A case report and literature review.

RATIONALE: Segmental zoster paresis (SZP) is a relatively rare neurologic complication of herpes zoster (HZ), and is characterized by focal asymmetric motor weakness in the myotome that corresponds to skin lesions of the dermatome. The upper extremities are the second most commonly involved regions after the face, and predominantly involve proximal muscles. The pathogenesis of SZP remains unclear; however, most of the reports indicate that it is the inflammation because of the spread of the herpes virus. PATIENT CONCERNS: A 72-year-old man without trauma history of the left shoulder joint developed weakness of the left proximal upper extremity 10 days after vesicular eruption of HZ. DIAGNOSES: His left shoulder girdle paresis was diagnosed with the upper truncus of the brachial plexus as a HZ complication according to a series of tests, including cervical magnetic resonance imaging (MRI), cerebral fluid analysis, sonography, and electrophysiological studies. INTERVENTIONS: Acyclovir and prednisolone were administered during hospitalization to treat SZP. Meanwhile, analgesics and gabapentin were administered to control the patient's neuralgic pain. He also received inpatient (daily) and outpatient (3 times per week) physical therapy along with range of motion and strengthening exercises. OUTCOMES: Partial improvement of the strength of the left shoulder girdle, and no improvement of the left deltoid muscle was observed 2 months after the interventions. LESSONS: This case emphasizes that HZ infections may be complicated by segmental paresis and they should be considered in the differential diagnosis of acute paresis in the upper limb. Awareness of this disorder is important because it avoids unnecessary invasive investigations and interventions, leading to suitable treatments with favorable prognosis.

Association between the characteristics of metabolic syndrome and Alzheimer's disease.

Various epidemiological studies have shown that type 2 diabetes and metabolic syndrome are highly correlated with Alzheimer's disease (AD). Here, we sought to assess the impact of metabolic syndrome characteristics on the progression of AD. Five-week-old male, spontaneously hypertensive (n = 32) and Wistar Kyoto (abbreviated WKY; n = 8) rats were divided into 5 groups (each n = 8): WKY, hypertension (HTN), streptozotocin-induced diabetes (STZ), high-fat diet (HFD), and STZ + high-fat diet-induced diabetes mellitus (DM). All animals were sacrificed and samples of the blood, liver, and brain were collected for further biological analysis. During the 15-week period of induction, the STZ and DM groups (animals injected with low-dose STZ) had significantly higher fasting glucose levels; the HFD group had elevated insulin levels, but normal blood glucose levels. The HFD and DM groups had hypercholesterolemia and higher hepatic levels of triglycerides and cholesterol. Additionally, correlations between HFD and elevated brain amyloid-beta 42 (Aß-42), hyperglycemia and down-regulation of brain insulin receptor, and serum Aß-42 and hepatic triglyceride concentrations (r(2) = 0.41, p < 0.05) were observed. Serum C-reactive protein and malondialdehyde did not appear to have a significant influence on the association with biomarkers of AD. Thus, our study demonstrated that rats with characteristics of metabolic syndrome had a large number of biomarkers predicting AD; however, no relationship between traditional inflammatory and oxidative markers and AD was found. Further studies are necessary to prove that these findings in rats are relevant to AD processes in humans.