Activation of MS as a result of bacterial and viral infections is proposed by various studies. However, immune responses initiated by a bacterial antigen can rarely lead to the activation or ...occurrence of MS. Hereby, we report a unique case of Multiple Sclerosis (MS) relapse following a Tuberculin skin test (TST). After one year of MS remission, a 13-years old female, presented with symptoms supporting tuberculosis (TB), although TST denied TB infection. Two weeks later, the patient returned with symptoms indicating MS relapse, confirmed by magnetic resonance imaging (MRI). A series of immune system interactions, starting with the activation of Toll-like receptors (TLRs) by Mycobacterial components, may expose the central nervous system (CNS) to autoimmune reactions. TST-induced type IV hypersensitivity can be another parallel mechanism in light of MS being a CD4 T-cell mediated disease. This case report highlights the importance of environmental factors such as bacterial agents in the pathophysiology of MS.
Abstract Background All orthopaedic procedures, comprising foot and ankle surgeries, seemed to show a positive trend, recently. Bone grafts are commonly employed to fix bone abnormalities resulting ...from trauma, disease, or other medical conditions. This study specifically focuses on reviewing the safety and efficacy of various bone substitutes used exclusively in foot and ankle surgeries, comparing them to autologous bone grafts. Methods The systematic search involved scanning electronic databases including PubMed, Scopus, Cochrane online library, and Web of Science, employing terms like 'Bone substitute,' 'synthetic bone graft,' 'Autograft,' and 'Ankle joint.' Inclusion criteria encompassed RCTs, case-control studies, and prospective/retrospective cohorts exploring different bone substitutes in foot and ankle surgeries. Meta-analysis was performed using R software, integrating odds ratios and 95% confidence intervals (CI). Cochrane's Q test assessed heterogeneity. Results This systematic review analyzed 8 articles involving a total of 894 patients. Out of these, 497 patients received synthetic bone grafts, while 397 patients received autologous bone grafts. Arthrodesis surgery was performed in five studies, and three studies used open reduction techniques. Among the synthetic bone grafts, three studies utilized a combination of recombinant human platelet-derived growth factor BB homodimer (rhPDGF-BB) and beta-tricalcium phosphate (β-TCP) collagen, while four studies used hydroxyapatite compounds. One study did not provide details in this regard. The meta-analysis revealed similar findings in the occurrence of complications, as well as in both radiological and clinical evaluations, when contrasting autografts with synthetic bone grafts. Conclusion Synthetic bone grafts show promise in achieving comparable outcomes in radiological, clinical, and quality-of-life aspects with fewer complications. However, additional research is necessary to identify the best scenarios for their use and to thoroughly confirm their effectiveness. Levels of evidence Level II.
Considering that ablation of atypical AVNRT may be unsuccessful after ablation at the right posterior septum, in this study, we aimed to present an optimal method for ablation of atypical AVNRT. ...Also, we evaluated the efficacy of this technique for preventing recurrences.
This is a prospective, double-center study. It was conducted on 62 patients with atypical AVNRT referred for radiofrequency ablation. The patients were randomly divided into two groups before ablation: 1-Group A (n = 30): treated with conventional ablation at the anatomic area of the slow pathway; 2-Group B (n = 32): ablation was done 2 mm higher in the septum during fluoroscopy.
The mean age of patients in groups A and B were 54 ± 11.7 and 55 ± 12.2, respectively (P = 0.43). In group A, ablation was successful in 24 (80%) patients following right-sided slow pathway ablation, and the remaining patients required further treatment with either a left-side approach (N = 4, 13.3%) or ablation of additional regions (N = 2, 6.7%). In group B, ablation was successful in all patients. After a 48-month follow-up, recurrence of symptomatic atypical AVNRT was detected in 4 (13.3%) patients of group A and none of group B patients (p < 0.001).
In patients with atypical AVNRT, ablation 2 mm above the conventional area is more promising regarding success rate and recurrence of the arrhythmia.
Frontal variant Alzheimer's disease (AD) manifests with either behavioral or dysexecutive syndromes. Recent efforts to gain a deeper understanding of this phenotype have led to a re-conceptualization ...of frontal AD. Behavioral (bAD) and dysexecutive (dAD) phenotypes could be considered subtypes, as suggested by both clinical and neuroimaging studies. In this review, we focused on imaging studies to highlight specific brain patterns in these two uncommon clinical AD phenotypes. Although studies did not compare directly these two variants, a common epicenter located in the frontal cortex could be inferred. On the contrary, 18F-FDG-PET findings suggested differing metabolic patterns, with bAD showing specific involvement of frontal regions and dAD exhibiting widespread alterations. Structural MRI findings confirmed this pattern, suggesting that degeneration might involve neural circuits associated with behavioral control in bAD and attentional networks in dAD. Furthermore, molecular imaging has identified different neocortical tau distribution in bAD and dAD patients compared to typical AD patients, although the distribution is remarkably heterogeneous. In contrast, Aβ deposition patterns are less differentiated between these atypical variants and typical AD. Although preliminary, these findings underscore the complexity of AD frontal phenotypes and suggest that they represent distinct entities. Further research is essential to refine our understanding of the pathophysiological mechanisms in frontal AD.
Long bone infected non-unions are such an orthopedic challenge that antibiotic-coated intramedullary nailing (ACIN) has become a viable therapeutic option for their management. This study aims to ...provide a comprehensive assessment of the available data about the use of antibiotic-coated nailing in the treatment of long bone infected non-unions. Following the PRISMA guideline in this meta-analysis, a systematic literature search was conducted across major databases for studies evaluating ACIN in long bone infected non-unions. The primary outcome measures included union rates, infection control, complications and functional status. Five eligible studies encompassing 183 patients in total met the inclusion criteria. The meta-analysis revealed no difference in the union rate in the antibiotic-coated intramedullary nailing group compared to that of the control group (OR = 1.73 0.75-4.02). Antibiotic-coated intramedullary nailing demonstrated no association with higher infection eradication (OR = 2.10 0.97-4.54). Also, functional outcome measure was mostly not significantly different between ACIN and control interventions. According to this meta-analysis, compared to the management of controls, ACIN is neither linked to increased union rates nor decreased infection rates. The paucity of research on this topic emphasizes the continuous need for additional well-designed randomized controlled trials for the application of antibiotics-coated intramedullary nailing in long bone non-unions.
The first appearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) named coronavirus disease 2019 (COVID-19) was reported from Wuhan in December 2019. While this virus displays ...several respiratory manifestations such as severe pneumonia and acute respiratory distress syndrome, there are several reports of nervous system involvement in the affected patients. Currently, there is a growing number of cases with central nervous system (CNS) autoimmune diseases (ADs) including autoimmune encephalitis (AE), neuromyelitis optica spectrum disorder (NMOSD), CNS vasculitis, acute disseminated encephalomyelitis (ADEM), and multiple sclerosis (MS) secondary to COVID-19 infection. Symptoms of these diseases vary from mainly drowsiness, delirium, and motor deficits in ADEM, MS, and AE and also visual impairment, and sensory problems in NMOSD and transverse myelitis patients. The severity of COVID-19 symptoms was also different from disease to disease. Based on the previous studies moderate corticosteroid therapy or other medication such as intravenous human immunoglobulins (IVIG), and plasma exchange (PLEX) is suggested for the treatment of CNS ADs in COVID patients. Also, patients with a previous history of ADs and other comorbidities such as hypertension, diabetes mellitus, hypercholesterolemia, and ischemic heart disease are at greater risk to develop severe complications of COVID compared to other patients. Current pieces of evidence demonstrated that CNS ADs can occur due to COVID-19 infection and the healthcare system should attention to CNS ADs as a complication of COVID-19. However, further investigations are strongly needed to confirm these findings.
Background
Proteinopathies as a consequence of cellular pathological pathways associated with Parkinson's disease (PD), leading to alteration of protein aggregation in cerebrospinal fluid (CSF). ...Rapid eye movement (REM) sleep behavior disorder (RBD is generally accepted as a prognostic factor predicting neurodegeneration, worse cognitive impairment, and the development of dementia PD.
Aim
Here we aimed to investigate the difference and longitudinal alteration of the CSF level of α-synuclein (α-syn), amyloid βeta (Aβ1-42), total tau (t-tau), and phosphorylated tau (p-tau) in PD subjects with RBD and without RBD.
Methods
We entered 413 early stage PD patients and 187 healthy controls (HCs) from PPMI. We compared the level of CSF biomarkers at baseline, 6 months, 1 year, and 2 years visits. In addition, we used linear mixed models to assess longitudinal changes of CSF proteins over 6 months, 1 year, and 2 years within groups.
Results
The level of CSF α-syn, Aβ1-42, t-tau, and p-tau was significantly higher in HCs compared to PD groups at any timepoint. In addition, there was a significantly lower CSF Aβ1-42 in PD–RBD subjects at 2 years timepoint (
p
= 0.020). There was no difference in CSF Aβ1-42 at other timepoints. Furthermore, comparisons between PD subjects with RBD and without RBD did not show any significant difference in CSF α-syn, t-tau, and p-tau at timepoints. The longitudinal analysis demonstrated that there was only a significant change in CSF level of Aβ1-42 after 1 year in PD patients with RBD (
p
= 0.031).
Conclusions
In our study, baseline values and longitudinal changes in CSF α-syn, t-tau, and p-tau were not remarkable enough to distinguish PD patients with and without RBD. Both of these groups demonstrated a stable trend in the longitudinal changes of these biomarkers. However, CSF Aβ1-42 seems to decrease in short follow-up and represents a significant difference after a while in PD patients with and without RBD. These findings suggested that CSF Aβ1-42 could be a more sensitive biomarker for early neurodegeneration and cognitive impairment in PD patients. The stable trend in other CSF biomarkers such as α-syn, t-tau, and p-tau can be justified by the fact that severe neurodegeneration may not be predictable in the early stages of PD patients.
Background
The prevalence of olfactory impairment in patients with Parkinson’s disease (PD) is 50–90%, and therefore, olfactory dysfunction is one of the most prevalent non-motor symptoms (NMSs) in ...patients with PD. Numerous studies have evaluated the association between motor and non-motor symptoms and olfactory dysfunction in PD.
Aim
In this study, we investigated the relationship between olfactory dysfunction, which is measured using the UPSIT test, with other motor and non-motor symptoms separately in three motor subtypes of PD, including tremor dominant (TD), postural instability and gait difficulty (PIGD), and indeterminate and healthy subjects.
Methods
We recruited 487 early-stage PD patients (43 PIGD, 406 TD, and 38 indeterminate) and healthy controls (HCs) (
n
= 197) from the Parkinson Progression Markers Initiative (PPMI). All participants completed motor and non-motor tests at baseline visit and after 4 years of follow-up. Subjects underwent common PD scaling tests.
Results
Olfactory dysfunction was significantly correlated with declined motor functions only in the TD subtype. Also, significant correlations were noticed between olfactory dysfunction and speed-attention processing and executive function in the HCs as well. Finally, no significant or meaningful association was observed in the PIGD and indeterminate subtype. Anosmia and hyposmia subjects in the TD group had the worse motor and non-motor scores compared to normosmia subjects after 4 years.
Conclusion
Olfactory dysfunction was significantly correlated with declined motor functions in the TD subtype. This is indicating that olfactory dysfunction may be an early motor and non-motor biomarker only in the TD subtype. However, it is possible that the involvement of olfactory function in other subtypes is not strong enough to make it a useful marker of diseases progression.
Background
Previous studies investigated CSF levels of α-synuclein (α-syn), amyloid-β (Aβ1-42), total tau (t-tau), and phosphorylated tau (p-tau) with clinical progression of Parkinson’s disease ...(PD). However, there is limited data on the association between CSF biomarkers and dopamine uptake status in PD.
Aim
In the current study, we aim to investigate the longitudinal association between striatal dopaminergic neuronal loss assessed by dopamine active transporter single photon emission computerized tomography (DaTSCAN) imaging with CSF α-syn, t-tau, p-tau, and Aβ1-42.
Methods
A total of 413 early-stage PD patients and 187 healthy controls (HCs) from the PPMI. Striatal binding ratios (SBRs) of DaTSCAN images in caudate and putamen nuclei were calculated. We investigated the cross-sectional and longitudinal association between CSF biomarkers and dopamine uptake using partial correlation models adjusted for the effect of age, sex, and years of education over 24 months of follow-up.
Results
The level of CSF α-syn, Aβ1-42, t-tau, and p-tau was significantly higher in HCs compared to PD groups at any time point. We found that higher CSF α-syn was associated with a higher SBR score in the left caudate at baseline (
P
= 0.038) and after 12 months (
P
= 0.012) in PD patients. Moreover, SBR scores in the left caudate and CSF Aβ1-42 were positively correlated at baseline (
P
= 0.021), 12 months (
P
= 0.006), and 24 months (
P
= 0.014) in patients with PD. Our findings demonstrated that change in CSF Aβ1-42 was positively correlated with change in SBR score in the left caudate after 24 months in the PD group (
P
= 0.043).
Conclusion
We found that cross-sectional levels of α-syn and Aβ1-42 could reflect the degree of dopaminergic neuron loss in the left caudate nucleus. Interestingly, longitudinal changes in CSF Aβ1-42 could predict the severity of left caudal dopaminergic neuron loss throughout the disease. This suggested that Aβ pathology might precede dopaminergic loss in striatal nuclei in this case left caudate and subsequently cognitive impairment in PD patients, although future studies are needed to confirm our results and expand the understanding of the pathophysiology of cognitive dysfunction in PD.
Background
Olfactory dysfunction is one of the earliest non-motor symptoms (NMS) in Parkinson’s disease (PD). There are contradictory results regarding the association of olfactory dysfunction and ...dopamine uptake in striatal nuclei among PD patients. It has been suggested that different motor subtypes of PD vary in the disease pathophysiology and progression. Thus, we hypothesized that there might be different associations between olfactory dysfunction and striatal dopaminergic neuronal loss among three motor subtypes of PD, namely, indeterminate, postural instability and gait difficulty (PIGD), and tremor-dominant (TD).
Methods
We recruited 162 healthy controls (HCs) and 464 drug-naïve PD patients from PPMI who underwent common PD scaling tests. Striatal binding ratios (SBRs) of DaTSCAN images in caudate and putamen nuclei were calculated. To assess the olfactory function, the University of Pennsylvania Smell Identification Test (UPSIT) was carried out.
Results
The UPSIT score was significantly correlated with MDS-UPDRS part I (
p
value: 0.002, correlation coefficient: − 0.160), MDS-UPDRS part III (
p
value: 0.000, correlation coefficient: − 0.248), and SBR score in right (
p
value: 0.000, correlation coefficient: 0.240) and left caudate (
p
value: 0.000, correlation coefficient: 0.221) and right (
p
value: 0.000, correlation coefficient: 0.323) and left putamen (
p
value: 0.000, correlation coefficient: 0.335) nucleus in TD subtype. There were no significant correlations in HC, PIGD, and indeterminate subjects.
Conclusion
The olfactory dysfunction was correlated with dopamine transporter activity in striatal nuclei only in the TD subtype. Therefore, the olfactory dysfunction in PIGD and indeterminate subtype may not be a predictive factor for the future decrease in dopamine uptake.
