Illustrated Neuropathologic Diagnosis of Alzheimer's Disease.

As of 2022, the prevalence of Alzheimer's disease (AD) among individuals aged 65 and older is estimated to be 6.2 million in the United States. This figure is predicted to grow to 13.8 million by 2060. An accurate assessment of neuropathologic changes represents a critical step in understanding the underlying mechanisms in AD. The current method for assessing postmortem Alzheimer's disease neuropathologic change follows version 11 of the National Alzheimer's Coordinating Center (NACC) coding guidebook. Ambiguity regarding steps in the ABC scoring method can lead to increased time or inaccuracy in staging AD. We present a concise overview of how this postmortem diagnosis is made and relate it to the evolving understanding of antemortem AD biomarkers.

CD24 gene allele variation is not associated with oligoclonal IgG bands and IgG index of multiple sclerosis patients.

OBJECTIVE: Multiple sclerosis (MS) shows evidence of many distinctive aspects of an autoimmune disorder, including a polygenic inheritance. A recent candidate gene for susceptibility to MS is CD24, which has also been shown to be associated with disease progression. This study was designed to examine whether there is a relationship between the CD24 genotype, oligoclonal band (OCB) status and IgG index in the cerebrospinal fluid (CSF) of MS patients. METHODS: A total of 27 definite MS patients were enrolled in this cross-sectional study. Blood samples were collected from a peripheral vein, and CSF was obtained by lumbar puncture. The CD24 gene was sequenced in the blood specimen, and albumin and IgG concentrations were measured in both CSF and serum. We compared both IgG index and OCB status in patients with and without CD24V/V. The correlation between MS severity score (MSSS), OCB status, CD24 genotype and IgG index was studied. RESULTS: Only 15 patients were OCB positive. Among patients with negative OCBs, only 2 patients had the V/V genotype. Furthermore, in those with the V/V genotype, IgG index was not significantly elevated (p = 0.322). Patients with the V/V genotype had a significantly higher MSSS (p = 0. 04), but neither the presence of OCBs nor the IgG index showed significant correlation with MSSS (p = 0.379 and 0.20, respectively). CONCLUSION: We could not show any relationship between the CD24V/V genotype, OCB status and IgG index. This could be interpreted as indicating that the CD24V/V allele exerts its effects on the disease course independently of CSF IgG synthesis.

Better prognosis of multiple sclerosis in patients who experienced a full-term pregnancy.

OBJECTIVE: We conducted a longitudinal prospective study to evaluate the long-term effect of pregnancy on the progression of multiple sclerosis (MS). METHOD: Parous female MS patients were extracted from the database of Isfahan multiple sclerosis society (IMSS). Through comparing the annual relapsing rate during a mean of 4 years before pregnancy versus a mean of 6 years after delivery, MS progression influenced by the pregnancy was analyzed. RESULT: 102 female patients were included in our study. The mean annual relapsing rate 4 years prior to pregnancy was significantly higher than at the subsequent 6 years after delivery (1.06 vs. 0.45, p < 0.001). In addition, the annual relapsing rate in years prior to pregnancy was significantly higher than each trimester of gestation (p < 0.001). Furthermore, there was a 2.2-fold increased risk of having a relapse in individuals who had experienced more relapses prior to pregnancy, and a 0.8-fold decreased in the risk of having more relapses with older age at the onset of MS. CONCLUSION: Although the course of MS was deteriorated 3 months after delivery, it was not statistically significant comparing annual relapsing rates during the years prior to pregnancy. Moreover, the rate of disease progression slowed down in the 6-year period monitored after delivery.

The key to an effective AI-powered digital pathology: Establishing a symbiotic workflow between pathologists and machine.

Pathology is a fundamental element of modern medicine that determines the final diagnosis of medical conditions, leads medical decisions, and portrays the prognosis. Due to continuous improvements in AI capabilities (e.g., object recognition and image processing), intelligent systems are bound to play a key role in augmenting pathology research and clinical practices. Despite the pervasive deployment of computational approaches in similar fields such as radiology, there has been less success in integrating AI in clinical practices and histopathological diagnosis. This is partly due to the opacity of end-to-end AI systems, which raises issues of interoperability and accountability of medical practices. In this article, we draw on interactive machine learning to take advantage of AI in digital pathology to open the black box of AI and generate a more effective partnership between pathologists and AI systems based on the metaphors of parameterization and implicitization.

SARS-CoV-2 and Acute Cerebrovascular Events: An Overview.

Since the coronavirus disease 2019 (COVID-19) pandemic, due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, accumulating evidence indicates that SARS-CoV-2 infection may be associated with various neurological manifestations, including acute cerebrovascular events (i.e., stroke and cerebral venous thrombosis). These events can occur prior to, during and even after the onset of COVID-19's general symptoms. Although the mechanisms underlying the cerebrovascular complications in patients with COVID-19 are yet to be fully elucidated, the hypercoagulability state, inflammation and altered angiotensin-converting enzyme 2 (ACE-2) signaling in association with SARS-CoV-2 may play key roles. ACE-2 plays a critical role in preserving heart and brain homeostasis. In this review, we discuss the current state of knowledge of the possible mechanisms underlying the acute cerebrovascular events in patients with COVID-19, and we review the current epidemiological studies and case reports of neurovascular complications in association with SARS-CoV-2, as well as the relevant therapeutic approaches that have been considered worldwide. As the number of published COVID-19 cases with cerebrovascular events is growing, prospective studies would help gather more valuable insights into the pathophysiology of cerebrovascular events, effective therapies, and the factors predicting poor functional outcomes related to such events in COVID-19 patients.

SARS-CoV-2 and nervous system: From pathogenesis to clinical manifestation.

Since the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a growing body of evidence indicates that besides common COVID-19 symptoms, patients may develop various neurological manifestations affecting both the central and peripheral nervous systems as well as skeletal muscles. These manifestations can occur prior, during and even after the onset of COVID-19 general symptoms. In this Review, we discuss the possible neuroimmunological mechanisms underlying the nervous system and skeletal muscle involvement, and viral triggered neuroimmunological conditions associated with SARS-CoV-2, as well as therapeutic approaches that have been considered for these specific complications worldwide.

Immunology of neuromyelitis optica during pregnancy.

Anti-aquaporin-4 (AQP4) autoantibody plays a key role in the pathogenesis of neuromyelitis optica (NMO). Studies have shown increased relapse rates in patients with NMO during pregnancy and postpartum. High estrogen levels during pregnancy can increase activation-induced cytidine deaminase expression, which is responsible for immunoglobulin production. Additionally, sex hormones may influence antibody glycosylation, with effects on antibody function. Estrogen decreases apoptosis of self-reactive B cells, through upregulation of antiapoptotic molecules. Furthermore, high estrogen levels during pregnancy can boost B-cell activating factor and type 1 interferon (IFN) production, facilitating development of self-reactive peripheral B cells in association with increased disease activity. Elevated levels of estrogen during pregnancy decrease IFN-γ generation, which causes a shift toward T helper (Th) 2 immunity, thereby propagating NMO pathogenesis. Women with NMO have an elevated rate of pregnancy complications including miscarriage and preeclampsia, which are associated with increased Th17 cells and reduction of T-regulatory cells. These in turn can enhance inflammation in NMO. Increased regulatory natural killer cells (CD56-) during pregnancy can enhance Th2-mediated immunity, thereby increasing inflammation. In the placenta, trophoblasts express AQP4 antigen and are exposed to maternal blood containing anti-AQP4 antibodies. Animal models have shown that anti-AQP4 antibodies can bind to AQP4 antigen in placenta leading to complement deposition and placental necrosis. Reduction of regulatory complements has been associated with placental insufficiency, and it is unclear whether these are altered in NMO. Further studies are required to elucidate the specific mechanisms of disease worsening, as well as the increased rate of complications during pregnancy in women with NMO.

Risk factors for remote seizure development in patients with cerebral vein and dural sinus thrombosis.

PURPOSE: We aimed to define the possible risk factors for acute and remote seizures in patients with cerebral vein and sinus thrombosis (CVST). METHOD: Ninety-four patients were recruited prospectively at Al-Zahra Hospital, Isfahan, Iran, between April 2007 and April 2012. To identify seizure predictors, we compared demographic, clinical and imaging factors between patients with or without acute and remote seizures. RESULTS: Of the 94 patients, 32 (34%) experienced at least one seizure after CVST development. Bivariate analysis showed a significant association of remote seizure with loss of consciousness at presentation (P=0.05, OR: 5.11, 95%CI: 1.07-24.30), supratentorial lesions (P=0.02, OR: 9.04, 95%CI: 1.04-78.55), lesions in the occipital lobe (P=0.00, OR: 12.75, 95%CI: 2.28-71.16), lesions in the temporal and parietal lobes, thrombophilia (P=0.03, OR: 5.87, 95%CI: 1.21-28.39), seizure in the acute phase (P=0.00, OR: 13.14, 95%CI: 2.54-201.2) and sigmoid sinus thrombosis (P=0.00, OR: 12.5, 95%CI: 2.23-69.79). Seizures in the acute phase were also more common in patients with paresis (P=0.00, OR: 4.88, 95%CI: 1.91-12.46), hemorrhagic lesions indicated by imaging (P=0.02, OR: 2.77, 95%CI: 1.08-7.10), supratentorial lesions, lesions in the frontal (P=0.01, OR: 3.81, 95%CI: 1.28-11.31) and parietal lobes (P=0.00, OR: 5.16, 95%CI: 2-13.29), thrombophilia and history of miscarriage (P=0.03, OR: 2.91, 95%CI: 1.07-7.91). No factor predicted acute or remote seizure in a multiple logistic regression analysis. CONCLUSION: Our results demonstrate that seizure development in the acute phase is the most significant factor for development of remote seizure. Parenchymal lesions in the supratentorial area were also found to be associated with both acute and remote seizures. However, no factor was predictive of acute or remote seizures in a multivariate analysis.

Autoimmune encephalitis associated with Graves' disease: a case report.

Almost all patients who developed autoimmune thyroid disease associated with encephalopathy were diagnosed to have Hashimoto's thyroiditis, but a few patients with Graves' disease who developed encephalopathy have been reported. A 36-year-old female with a 10-year history of Graves' disease had experienced three episodes of tonic-clonic seizure. At admission, the patient's status was confused, and she also developed tactile and visual hallucinations. The cranial MRI confirmed white-matter lesion and showed subcortical high signal lesions on T2-weighted images. In EEG record, diffuse slow activity was noticed in both sides. T3 and TSH were decreased, T4 remained normal and thyroid peroxidase antibody (TPO) was evaluated to be more than 2,000 (T4 = 8.4, T3 = 12/9, TSH = 0/14, TPO >2,000). The diagnosis of autoimmune thyroid disease is probable in all patients with signs of encephalopathy with unknown origin, while they have a previous history of thyroid disease.

The effect of statin therapy in stroke outcome: a double blind clinical trial.

BACKGROUND: Through a clinical trial we evaluated statin therapy benefits over stroke outcome. METHODS: All patients with moderate stroke in Middle Cerebral Artery (MCA) were registered during February 2006 to February 2008, in Al Zahra Hospital, Isfahan, Iran. Among 55 patients who were enrolled in the present study, 25 subjects received 20 mg lovastatin daily, for 90 days after stroke attack (group 1) and 30 patients received no treatment (group 2). Patients were assessed at admission, 7 and 90 days after stroke. National Institutes of Health Stroke Scale (NIHSS) score was recorded in the day 1 and 7 in the hospital with a questionnaire and BARTHEL index was estimated 90 days after stroke incidence by a telephone survey or in an outpatient visit. Data were analyzed by means of χ(2), 't' test and Independent 't' test. RESULTS: NIHSS score measured in first day immediately after stroke attack and following 7 days, did not differ significantly in two groups. Moreover, BARTHEL index recorded within 90 days was not also different comparing group 1 and 2. After 90 days, no mortality was recorded in group 2, while one patient expired in group treating with statins (P-value>0.05). DISCUSSION: We did not find statins administration to play any role in stroke recovery and consequent long-term prognosis. More researches with larger samples are needed to establish the possible favorable outcome of statins when administered in cerebrovascular diseases.

Serum mercury level and multiple sclerosis.

Exposure to heavy metals has been associated to a higher incidence of multiple sclerosis. In this work, we present a possible relationship between serum mercury levels and development of multiple sclerosis in Isfahan, the third largest city in Iran. Seventy-four patients affected by multiple sclerosis were retrieved from multiple sclerosis (MS) clinic in Isfahan, Iran. By matching sex and age, 74 healthy volunteers were chosen as control group. Blood samples were collected and serum mercury content was determined. Serum mercury level in MS patients was significantly higher than controls (9.6 ± 10.17 vs. 5.7 ± 8.6, P = 0.037). Concerning all MS patients, serum mercury value was significantly higher than the mercury concentration founded in control subjects {odd ratio: 2.39 (CI, 1.96-2.94), P = 0.00}. Serum mercury level is higher in MS patients with odd ratio equal to 2.39 compared with healthy individuals. It may reveal that high mercury levels in serum might help MS development in susceptible individuals. More studies with larger sample size are needed to confirm this hypothesis.