Course Of Disease Research Articles

Non-syndromic OTX2-associated pattern dystrophy: a 10-year multimodal imaging study.

To report novel multimodal imaging features and long-term follow-up of Orthodenticle Homeobox 2 (OTX2)-associated pattern Gdystrophy. A 14-year-old boy referred with glaucoma suspect and macular pigmentation underwent fundus autofluorescence imaging, optical coherence tomography, fluorescein and indocyanine green angiography, visual field test, microperimetry and electrophysiology over a ten-year period. Next-generation sequencing panel identified a de novo heterozygous likely pathogenic OTX2 variant, c.259G>A, [p.(Glu87Lys)]. Visual acuity was 20/40 OD and 20/30 OS. Examination showed bilateral enlarged optic nerve heads and increased disc cupping, multiple cilioretinal arteries, a pigmentary maculopathy with stellate-shaped region of hypoautofluorescence, shallow serous macular detachment, subretinal deposits and temporal avascular retina. Angiography showed no source of leakage and absence of retinal neovascularisation despite extensive peripheral non perfusion. Electrophysiological assessments demonstrated mild progressive rod and cone pathway abnormalities, reduced light-adapted b:a ratio, and reduced Arden ratio on electro-oculogram. Ten-year follow-up confirmed a stable disease course despite persistent submacular fluid. There was no associated pituitary structural abnormality or dysfunction. This case study contributes to further understanding of OTX2-associated pattern dystrophy, highlighting its stability over 10 years. Further investigation into inter-individual and intrafamilial variability is warranted.

Palliative neurology

Palliative medicine represents the holistic multiprofessional treatment of severely and incurably ill people and their relatives, addressing their complex physical, psychological, social and spiritual needs. The central therapeutic goals are the quality of life and alleviation of suffering. In the course of many neurological diseases, high symptom burden, long and variable trajectories and unfavorable prognosis at times create aneed for palliative care even at an early stage, which is currently still inadequately met. This can be countered by qualified neuropalliative care. In addition to intensifying interdisciplinary collaboration, this requires neurologists to have core competencies in palliative care. These include ateam-oriented attitude, communication skills, expertise in symptom control and knowledge of biomedical ethics including palliative options at the end of life.

Patient-Centered Management of Brain Tumor-Related Epilepsy.

Brain tumor-related epilepsy is a heterogenous syndrome involving variability in incidence, timing, pathophysiology, and clinical risk factors for seizures across different brain tumor pathologies. Seizure risk and disability are dynamic over the course of disease and influenced by tumor-directed treatments, necessitating individualized patient-centered management strategies to optimize quality of life. Recent translational findings in diffuse gliomas indicate a dynamic bidirectional relationship between glioma growth and hyperexcitability. Certain non-invasive measures of hyperexcitability are correlated with survival outcomes, however it remains uncertain how to define and measure clinically relevant hyperexcitability serially over time. The extent of resection, timing of pre-operative and/or post-operative seizures, and the likelihood of tumor progression are critical factors impacting the risk of seizure recurrence. Newer anti-seizure medications are generally well-tolerated with similar efficacy in this population, and several rapid-onset seizure rescue agents are in development and available. Seizures in patients with brain tumors are strongly influenced by the underlying tumor biology and treatment. An improved understanding of the interactions between tumor cells and the spectrum of hyperexcitability will facilitate targeted therapies. Multidisciplinary management of seizures should occur with consideration of tumor-directed therapy and prognosis, and anti-seizure medication decision-making tailored to the individual priorities and quality of life of the patient.

A multicenter study of long-term outcomes of relapsing polychondritis in Iran

Relapsing polychondritis (RP) is a systemic immune mediated disease characterized by recurrent episodes of inflammation in various cartilage-rich areas. RP may cause extensive tissue destruction and is associated with significant morbidity and mortality. In this multicenter study, we considered the remission status and long-term outcomes of RP in patients who were followed-up in six referral rheumatology centers in Iran. Outcomes of disease was assessed by remission status and RP induced damage. A total of 29 patients with RP were examined for enrollment in the study, and 26 patients with a minimum follow-up period of 6 months were included in the RP outcome analysis. Median time to control of symptoms and sustained remission were 5 and 23 weeks, respectively. Prednisolone was discontinued in 8 (30.8%) patients and medication-free remission was achieved in 7 (23.1%) patients. Regarding the disease course, 34.6% of patients had a relapsing–remitting course, 42.3% had a monophasic course, and 23.1% had an always-active course. Despite extensive treatment with immunosuppressive medications, RP induced damage was developed in 21 (80.8%) patients. Ear deformity and osteoporosis were the most common RP induced damage. Long-term remission and medications-free remission in RP is accessible. However, RP related damage occur in majority of patients.

Infantile and Very Early Onset Inflammatory Bowel Disease: A Multicenter Study.

This study described disease characteristics and long-term outcomes in patients diagnosed with very early onset inflammatory bowel disease (VEOIBD) (diagnosed before 6 years of age) and infantile-IBD (before 2 years). Cases from 21 centers worldwide diagnosed with VEOIBD (2008-2018), with minimum 2 years of follow-up, were retrospectively reviewed. The cohort included 243 patients (52% males, median follow-up of 5.8 [range 2-18] years, including 69 [28%]) with infantile-IBD. IBD subtypes included Crohn's disease (CD), ulcerative colitis (UC), or IBD-unclassified (IBDU) in 30%, 59%, and 11%, respectively. Among patients with CD, 94% had colonic involvement, and among patients with UC/IBDU, 75% had pancolitis. Patients with infantile-IBD presented with higher rates of IBDU, lower hemoglobin and albumin levels, and higher C-reactive protein, and had lower response rates to first-induction therapy and corticosteroids therapy (P < .05 for all). Colectomy and diversion surgeries were performed in 11% and 4%, respectively, with no significant differences between age groups. Corticosteroid-free remission rates were 74% and 78% after 3 and 5 years, respectively, and 86% at end of follow-up. Genetic testing was performed in 96 (40%) patients. Among tested population, 15 (16%) were identified with monogenic disease. This group demonstrated lower response rates to induction therapies, higher rates of surgical intervention, and higher rates of major infections (P < .05 for all). Patients with VEOIBD, including infantile-IBD, exhibit low rate of complications and surgical interventions at the long term. Patients with monogenic IBD are at risk for more severe disease course.

Occupational interstitial lung diseases

Avariety of workplace exposures (organic or inorganic dusts as well as gases, fumes, or vapors) can cause diffuse interstitial lung disease. The latency period until onset of the disease can exceed 30years. The disease course varies greatly and depends on the quantity of the inhaled substance and its fibrogenic effect. Pulmonary high-resolution computed tomography (HRCT) patterns do not differ significantly from those of interstitial lung diseases (ILD) of other etiologies. Therefore, without knowledge of the occupational history, work-related ILDs are often classified as idiopathic. In addition, there is increasing evidence in the recent literature that high exposure to silica dust can trigger autoimmune diseases (also involving the lungs). For this reason, aqualified occupational history is now an indispensable part of the interdisciplinary diagnosis of ILDs.

Gut microbial factors predict disease severity in a mouse model of multiple sclerosis.

Gut bacteria are linked to neurodegenerative diseases but the risk factors beyond microbiota composition are limited. Here we used a pre-clinical model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE), to identify microbial risk factors. Mice with different genotypes and complex microbiotas or six combinations of a synthetic human microbiota were analysed, resulting in varying probabilities of severe neuroinflammation. However, the presence or relative abundances of suspected microbial risk factors failed to predict disease severity. Akkermansia muciniphila, often associated with MS, exhibited variable associations with EAE severity depending on the background microbiota. Significant inter-individual disease course variations were observed among mice harbouring the same microbiota. Evaluation of microbial functional characteristics and host immune responses demonstrated that the immunoglobulin A coating index of certain bacteria before disease onset is a robust individualized predictor of disease development. Our study highlights the need to consider microbial community networks and host-specific bidirectional interactions when aiming to predict severity of neuroinflammation.

The effect of vitamin D on the development of Hashimoto's disease and the reduction of the inflammatory process in its course - review

Introduction Hashimoto's disease is an autoimmune chronic lymphocytic thyroiditis. It is a common condition, more frequent in women. Its diagnosis is based on the presence of specific antithyroid antibodies in the patient's blood which lead to the destruction of the thyroid gland. This can result in the development of hypothyroidism, requiring levothyroxine replacement therapy. Aim of the review A summary of the information gathered so far on the involvement of vitamin D in the development and course of Hashimoto's disease. Results The articles analyzed have mixed results. Most of them show a positive correlation between vitamin D and Hashimoto's disease, paying particular attention to the contribution of vitamin D in moderating the inflammatory process in HT. Other studies show significant differences in vitamin D levels between groups with different HT severity. Others show a negative correlation between vitamin D levels and the development of Hashimoto's disease. Conclusions Large well-controlled randomized double blind trials are needed in order to determine the exact role of vitamin D in Hashimoto’s disease.

BİOLOGİYA FƏNNİ ÜZRƏ ON BİRİNCİ SİNİFLƏRİNDƏ TƏDRİS OLUNAN MÖVZULARLA ƏLAQƏDAR VALİOLOJİ BİLİKLƏRİN İNTERAKTİV YOLLARLA ÖYRƏNİLMƏSİ XÜSUSİYYƏTLƏRİ

Summary In the eleventh grade of the school, the role of microorganisms in the course of infectious processes associated with human health, the role of the host organism in the occurrence of infectious processes, the influence of environmental conditions on the course of infectious diseases are directed. When mastering valeological knowledge. Students are given knowledge about the ways of developing skills for valeological knowledge to carry out urgent preventive measures for the timely prevention of defects caused by infectious diseases in the human body. Key words: infectious diseases, microorganisms, host organisms, valeological knowledge, human health

Prognostic efficiency of diagnostic blockade as a method of modeling the result of selective neurotomy of the motor branches of the median nerve in patients with cerebral palsy

BACKGROUND: A feature of the disease course in patients with spastic cerebral palsy is a combination of motor neurological disorders with contractures in extremity joints. Neurosurgical methods are currently the main treatment for correcting the pathological tone of the “spastic hand.” However, the decreased tone does not affect secondary (fixed) contractures; therefore, the effectiveness of this type of treatment is extremely dependent on the accurate selection of a certain category of patients. Presumably, diagnostic blockade of the median nerve can create a reversible model for planned neurosurgical treatment. The inclusion of this technique as a standard for examining a patient with spastic cerebral palsy before invasive tone-lowering treatment can radically promote treatment effectiveness. AIM: This study aimed to assess the prognostic effectiveness of diagnostic blockade as a method of modeling the result of selective neurotomy of the motor branches of the median nerve in patients with cerebral palsy. MATERIALS AND METHODS: A longitudinal prospective study enrolled 39 children (aged 5–18 years) with spastic cerebral palsy. Before neurosurgical treatment, each patient underwent a diagnostic n. medianus under electrical stimulation and ultrasound control. After a diagnostic blockade, only patients who had a good functional and goniometric response were selected for the study, which served as an indication for selective neurotomy of the median nerve, and orthopedic treatment was performed in children with a negative event. Patients referred for neurotomy underwent a standardized examination before treatment during the diagnostic blockade and after neurosurgical treatment. The examination included the assessment of the amplitude of passive and active movements in the joints of the upper extremities, muscle tone, and functional capabilities of the upper extremities and dynamometry. RESULTS: In comparison with the initial data, a significant increase in the amplitude of passive and active hand extension, passive and active abduction of the first finger, and upper limb functional capabilities according to the MACS classification and the Miller scale was determined both after the diagnostic blockade and after selective neurotomy of the motor branches of the median nerve. CONCLUSIONS: Based on the results of the study, the effect of the diagnostic blockade and neurosurgical treatment outcomes are unidirectional, which allows the use of blockade as a method for modeling the possible result in clinically complex cases of spastic hand. The use of diagnostic blockade in clinical practice makes it possible to adequately assess the severity of fixed contractures and reduce the pathological hypertonicity of the target muscles. Diagnostic blockade allows for the collection of sufficient information to make an objective decision about which type of treatment is most preferable for each patient – neurosurgical, orthopedic, or sequential use of both methods.

The Role of Vitamin D and Vitamin D Receptor Gene Polymorphisms in the Course of Inflammatory Bowel Disease in Children

Background: The etiopathogenesis of inflammatory bowel disease (IBD) is still unclear. Prior studies suggest genetic components that may influence the incidence and severity of the disease. Additionally, it was shown that low levels of serum vitamin D may have an impact on the clinical course of the disease due to its effect on the immunological system. Methods: We aimed to investigate the correlation between the incidence of vitamin D receptor (VDR) gene polymorphisms (rs11568820, rs10735810, rs1544410, rs7975232, and rs731236, commonly described as Cdx2, FokI, Bsm, ApaI, and TaqI, respectively) and vitamin D concentration with the clinical course of IBD (disease activity, extent of the intestinal lesions). Data were obtained from 62 patients with IBD (34 with Crohn’s disease, 28 with ulcerative colitis), aged 3–18 years, and compared with controls (N = 47), aged 8–18 years. Results: Although there was no difference in the incidence of individual genotypes between the study groups (IBD, C) in all the polymorphisms examined, we described a significant increase in the chance of developing IBD for heterozygotes of Cdx2 (OR: 2.3, 95% CI 0.88–6.18, p = 0.04) and BsmI (OR: 2.07, 95% CI 0.89–4.82, p = 0.048) polymorphisms. The mean serum 25OHD level in patients with IBD was significantly higher compared with the controls (19.87 ng/mL vs. 16.07 ng/mL; p = 0.03); however, it was still below optimal (&gt;30 ng/mL). Furthermore, a significant correlation was found between vitamin D level and TaqI in patients with IBD (p = 0.025) and patients with CD (p = 0.03), as well as with the BsmI polymorphism in patients with IBD (p = 0.04) and patients with CD (p = 0.04). A significant correlation was described between the degree of disease activity and genotypes for the FokI polymorphism in patients with UC (p = 0.027) and between the category of endoscopic lesions and genotypes for the Cdx2 polymorphism also in patients with UC (p = 0.046). Conclusions: The results suggest a potential correlation of VDR gene polymorphism with the chance of developing IBD, and the clinical course of the disease requires further studies in larger group of patients. Vitamin D supplementation should be recommended in both children with inflammatory bowel disease and in healthy peers.

Comprehensive Study of the IBMP ELISA IgA/IgM/IgG COVID-19 Kit for SARS-CoV-2 Antibody Detection

COVID-19 laboratory diagnosis primarily relies on molecular tests, highly sensitive during early infection stages with high viral loads. As the disease progresses, sensitivity decreases, requiring antibody detection. Since the beginning of the pandemic, serological tests have been developed and made available in Brazil, but their diagnostic performance varies. This study evaluated the IBMP ELISA IgA/IgM/IgG COVID-19 kit performance in detecting SARS-CoV-2 antibodies. A total of 90 samples, including 64 from COVID-19 patients and 26 pre-pandemic donors, were assessed based on time post symptom onset (0–7, 8–14, and 15–21 days). The kit showed 61% sensitivity, 100% specificity, and 72% accuracy overall. Sensitivity varied with time, being 25%, 57%, and 96% for 0–7, 8–14, and 15–21 days, respectively. Similar variations were noted in other commercial tests. The Gold ELISA COVID-19 (IgG/IgM) had sensitivities of 31%, 71%, and 100%, while the Anti-SARS-CoV-2 NCP ELISA (IgG) and Anti-SARS-CoV-2 NCP ELISA (IgM) showed varying sensitivities. The IBMP ELISA kit displayed high diagnostic capability, especially as the disease progressed, complementing COVID-19 diagnosis. Reproducibility assessment revealed minimal systematic and analytical errors. In conclusion, the IBMP ELISA IgA/IgM/IgG COVID-19 kit is a robust tool for detecting anti-SARS-CoV-2 antibodies, increasing in efficacy over the disease course, and minimizing false negatives in RT-PCR COVID-19 diagnosis.

Is a vegetarian diet beneficial for bipolar disorder? Relationship between dietary patterns, exercise and pharmacological treatments with metabolic syndrome and course of disease in bipolar disorder.

Lifestyle factors are being increasingly studied in bipolar disorder (BD) due to their possible effects on both course of disease and physical health. The aim of this study was to jointly describe and explore the interrelations between diet patterns, exercise, pharmacological treatment with course of disease and metabolic profile in BD. The sample consisted of 66 euthymic or mild depressive individuals with BD. Clinical and metabolic outcomes were assessed, as well as pharmacological treatment or lifestyle habits (diet and exercise). Correlations were explored for different interrelations and a factor analysis of dietary patterns was performed. Adherence to the Mediterranean diet was low, seen in 37.9% of the patients and was positively associated with perceived quality of life. The amount of exercise was negatively associated with cholesterol levels, with 32.8% of participants rated as low active by International Physical Activity Questionnaire. There was a high prevalence of obesity (40.6%) and metabolic syndrome (29.7%). Users of lithium showed the best metabolic profile. Interestingly, three dietary patterns were identified: "vegetarian," "omnivore" and "Western." The key finding was the overall positive impact of the "vegetarian" pattern in BD, which was associated with reduced depression scores, better psychosocial functioning, and perceived quality of life, decreased body mass index, cholesterol, LDL and diastolic blood pressure. Nuts consumption was associated with a better metabolic profile. A vegetarian diet pattern was associated with both, better clinical and metabolic parameters, in patients with BD. Future studies should prioritize prospective and randomized designs to determine causal relationships, and potentially inform clinical recommendations.

Faecal biomarkers for diagnosis and prediction of disease course in treatment-naïve patients with IBD.

Faecal biomarkers can be used to assess inflammatory bowel disease (IBD). To explore the performance of some promising biomarkers in diagnosing and predicting disease course in IBD. We included 65 patients with treatment-naïve, new-onset Crohn's disease (CD), 90 with ulcerative colitis (UC), 67 symptomatic controls (SC) and 41 healthy controls (HC) in this prospective observational study. We analysed faecal samples for calprotectin (FC), myeloperoxidase (MPO), human neutrophil lipocalin (HNL), eosinophil cationic protein ECP and eosinophil-derived neurotoxin (EDN) and compared markers among groups. We assessed the diagnostic capability of biomarkers with receiver operating characteristic curves. Clinical disease course was determined for each patient with IBD and analysed the association with biomarkers by logistic regression. All markers were elevated at inclusion in patients with IBD compared with HC (p < 0.001) and SC (p < 0.001). FC (AUC 0.85, 95% CI: 0.79-0.89) and MPO (AUC 0.85, 95% CI: 0.80-0.89) showed the highest diagnostic accuracy in distinguishing IBD from SC. The diagnostic ability of biomarkers differed between IBD subtypes with the highest performance for FC and MPO in CD. The diagnostic accuracy was further improved by combining FC and MPO (p = 0.02). Levels of FC, MPO and HNL at inclusion were predictive of an aggressive disease course with MPO showing the strongest association (p = 0.006). This studyprovides new insight into the diagnostic and prognostic capability of neutrophil and eosinophil biomarkers in IBD and suggests that MPO, alone or in combination with FC, may add to the diagnostic power of faecal biomarkers.

Effects of low-dose methotrexate with MMI in patients with Graves' disease: results of a randomized clinical trial.

Supplemental methotrexate (MTX) may affect the clinical course of Graves' disease (GD). Evaluate efficacy of add-on MTX on medical treatment in GD. Prospective, open-label, randomized supplementation controlled trial. Academic endocrine outpatient clinic. One hundred and fifty-three untreated hyperthyroid patients with GD. Patients received MTX 10 mg/d with methimazole (MMI) or MMI only. MTX and MMI were discontinued at months 12-18 in euthyroid patients. Discontinuation rate at months 18 in each group. In the MTX with MMI group, the discontinuation rate was higher than the MMI group at months 15-18 (50.0 vs. 33.3%, P=0.043, 95% CI 1.020 to 3.922; and 55.6 vs 38.9%, P=0.045, 95%CI 1.011 to 3.815, respectively). The decrease in TRAb levels in the MTX with MMI group was significant from baseline to months 6 compared to the MMI alone group [MTX+MMI 67.22% (43.12-80.32), MMI 54.85% (33.18-73.76), P= 0.039) and became more significant from months 9 [MTX+MMI 77.79% (62.27-88.18), MMI 69.55% (50.50-83.22), P= 0.035] to months 18 (P < 0.01 in 15-18 months). A statistically significant difference between the levels of TRAb in the MTX with MMI group and the MMI group at 9-18 months. There were no significant differences in the levels of FT3, FT4 and TSH between two groups. No serious drug-related adverse events were observed in both groups(P=0.771). Supplemental MTX with MMI resulted in higher discontinuation rate and improvement in decreased TRAb levels to homeostatic levels faster than methimazole treatment alone at months 12-18.

Unobvious long-term effects of COVID-19 for kidneys. The literature review

The impact of COVID-19 on the course of chronic kidney disease (CKD) has already been confirmed by researchers around the world. Basically, studying kidney damage in COVID-19, the authors pay attention to the new coronavirus infection in terms of the development of acute kidney injury (AKI) or mortality from it in patients with existing CKD, especially patients receiving hemodialysis or having a transplanted kidney, providing an analysis of mortality, risks and forecasts. However, there is still no published description of how this infection can affect the function of kidneys that did not have signs of CKD before COVID-19. Currently, studies devoted to the analysis of long-term results of observation and treatment of such patients are especially scarce. The review examines foreign and domestic studies concerning both the influence of chronic kidney disease on the severity of coronavirus infection and the risks of developing kidney disease after COVID-19, including the development of acute kidney injury and in the long term. This approach can highlight the relevance of timely identification of patients with developing CKD in the early stages among patients with COVID-19 for the purpose of their further follow-up and timely prescription of nephroprotective therapy. The search for literature sources was carried out using PubMed, Science Direct, eLibrary using the keywords “coronavirus”, “COVID-19”, “SARS-CoV-2”, “acute kidney injury”, “chronic kidney disease” and their combinations covering publications from 2019 to 2023 in Russian and English.

A comparison of clinical characteristics and course predictors in early- and childhood-onset schizophrenia.

The aim of this study was to compare the clinical characteristics of childhood-onset schizophrenia (COS) and early-onset schizophrenia (EOS) during the first- episode psychosis and the stable period, to examine psychopharmacological treatment approaches, and to investigate potential predictive factors for prognosis. Demographic, clinical, and psychopharmacological therapy data for 31 patients diagnosed with COS and 66 with EOS were retrieved from the file records in this multicenter study. Symptom distribution and disease severity and course were evaluated twice, in the acute psychotic stage and in the latest stable phase, during follow-up using the positive and negative syndrome scale (PANSS) and clinical global impression (CGI) scales. A statistically significant difference was observed between the groups' CGI improvement rates and median last stable stage PANSS positive, negative, and general psychopathology symptom scores (p = .005, p = .031, p = .005, and p = .012, respectively). Premorbid neurodevelopmental disorder and obsessive-compulsive disorder and comorbidities were more common in the COS group (p = .025 and p = .030, respectively), and treatment required greater multiple antipsychotic use in that group (p = .013). When the independent variables affecting the difference between pre- and post-treatment PANSS scores were examined using linear regression analysis, the model established was found to be statistically significant (F = 5.393; p = .001), and the group variable (p = .024), initial disease severity (p = .001), and socioeconomic level (p = .022; p = .007) emerged as predictive factors for the disease course. Although early diagnosis and treatment is an important factor in improving prognosis in schizophrenia, more specific predictors for schizophrenia need to be identified. Additionally, preventive programs and pharmacological methods need to be developed in children with neurodevelopmental problems, particularly those from low socioeconomic status families.

Differences in Clinical Practice and Disease Course between Elderly-Onset and Long-Standing Elderly Ulcerative Colitis: A Single-Center Study in Japan.

Differences in Clinical Practice and Disease Course between Elderly-Onset and Long-Standing Elderly Ulcerative Colitis: A Single-Center Study in Japan.

Preventing long-term disability in CIDP: the role of timely diagnosis and treatment monitoring in a multicenter CIDP cohort.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an inflammatory disease affecting the peripheral nerves and the most frequent autoimmune polyneuropathy. Given the lack of established biomarkers or risk factors for the development of CIDP and patients' treatment response, this research effort seeks to identify potential clinical factors that may influence disease progression and overall treatment efficacy. In this multicenter, retrospective analysis, we have screened 197 CIDP patients who presented to the University Hospitals in Düsseldorf, Berlin, Cologne, Essen, Magdeburg and Munich between 2018 and 2022. We utilized the respective hospital information system and examined baseline data with clinical examination, medical letters, laboratory results, antibody status, nerve conduction studies, imaging and biopsy findings. Aside from clinical baseline data, we analyzed treatment outcomes using the Standard of Care (SOC) definition, as well as a comparison of an early (within the first 12months after manifestation) versus late (more than 12months after manifestation) onset of therapy. In terms of treatment, most patients received intravenous immunoglobulin (56%) or prednisolone (39%) as their first therapy. Patients who started their initial treatment later experienced a worsening disease course, as reflected by a significant deterioration in their Inflammatory Neuropathy Cause and Treatment (INCAT) leg disability score. SOC-refractory patients had worse clinical outcomes than SOC-responders. Associated factors for SOC-refractory status included the presence of fatigue as a symptom and alcohol dependence. Timely diagnosis, prompt initiation of treatment and careful monitoring of treatment response are essential for the prevention of long-term disability in CIDP and suggest a "hit hard and early" treatment paradigm.

Clinical and diagnostic implications of Alzheimer's disease copathology in Lewy body disease.

Concomitant Alzheimer's disease (AD) pathology is a frequent event in the context of Lewy body disease (LBD), occurring in approximately half of all cases. Evidence shows that LBD patients with AD copathology show an accelerated disease course, a greater risk of cognitive decline and an overall poorer prognosis. However, LBD-AD cases may show heterogeneous motor and non-motor phenotypes with higher risk of dementia, and, consequently, be not rarely misdiagnosed. In this review, we summarize the state-of-the-art on LBD-AD by discussing the synergistic effects between AD neuropathological changes and Lewy pathology and their clinical relevance. Furthermore, we provide an extensive overview of neuroimaging and fluid biomarkers under assessment in LBD-AD and their possible diagnostic and prognostic value. AD pathology can be suspected in vivo by means of CSF, MRI and PET markers, whereas α-synuclein seed amplification assays (SAAs) represent to date the most promising technique to identify Lewy pathology in different biological tissues. Pathological imaging and CSF AD biomarkers are associated with a higher likelihood of cognitive decline in LBD but do not always mirror the neuropathological severity like in pure AD. The implementation of blood-based biomarkers of AD might allow the fast screening of LBD patients for AD copathology, thus improving the overall diagnostic sensitivity for LBD-AD. Finally, we discuss the literature on novel candidate biomarkers being exploited in LBD-AD to investigate other aspects of neurodegeneration, such as neuroaxonal injury, glial activation and synaptic dysfunction. The thorough characterization of AD copathology in LBD should be taken into account for the differential diagnosis of dementia syndromes, for the prognostic evaluation on an individual level and for guiding symptomatic and disease-modifying therapies.