Journal of Central Nervous System Disease最新文献

New-onset refractory status epilepticus (NORSE) is a rare and devastating condition and the prognosis is often poor, with half to two-thirds of survivors experiencing drug-resistant epilepsy, residual cognitive impairment, or functional disability, and the mortality rate is 16% to 27% for adults. We describe a patient with cryptogenic NORSE and favorable recovery from drug-resistant super-refractory SE after the use of intravenous lidocaine. The patient experienced fever and presented with refractory generalized tonic-clonic seizures. The cause was not found by performing extensive examinations, including cell surface autoantibodies and rat brain immunohistochemistry evaluations. The refractory SE with unresponsiveness to multiple anti-epileptic and prolonged sedative medications, which are necessary for prolonged mechanical ventilation, were ameliorated by additive treatment with intravenous lidocaine initiating at 1 mg/kg/h and maintaining at 2 mg/kg/h for 40 days, which led to freedom from intravenous sedative medication and mechanical ventilation. The patient was able to return to school. Lidocaine may be an optional treatment for cryptogenic NORSE.

Background: Early neurological deterioration (END) is a common occurrence in ischemic stroke and contributes significantly to poor outcomes. Although multiple factors that predict END have already been identified, the role of fibrinogen - a key component of the coagulation pathway, is controversial.

Objective: To assess the role of fibrinogen in predicting END and poor hospital outcome in patients with acute ischemic stroke.

Design: Single-centre prospective observational study.

Methods: 141 patients with acute ischemic stroke were analyzed in this prospective observational study from a single tertiary-care hospital in East India. END was defined as a worsening of ≥2 points on the National Institutes of Health Stroke Scale (NIHSS) within 7 days of admission. A score of 3-5 on the Modified Rankin Scale (mRS), a stroke recurrence event or death during hospital stay was considered poor hospital outcome. We performed univariate analysis using age, sex, body-mass index (BMI), hypertension, diabetes, NIHSS scores, stroke etiology, blood glucose and lipid parameters and plasma fibrinogen to develop a logistic regression model to establish the independent predictors of END and poor outcome.

Results: Age (Odds Ratio (OR) 1.034 [95% CI 1.001-1.069], P = .046), NIHSS score at admission (OR 1.152 [95% CI 1.070-1.240], P < .001) and fibrinogen (OR 1.011 [95%CI 1.006-1.015], P < .001) were independent predictors of END in patients with acute ischemic stroke. Factors independently associated with poor outcome were NIHSS score at admission (OR 1.257 [95% CI 1.150-1.357], P < .001), fasting plasma glucose (OR 1.007 [95% CI 1.001-1.013], P = .020), and fibrinogen [OR 1.004 [95% CI 1.000-1.007], P = .038).

Conclusion: The significant role of fibrinogen in determining neurological worsening and subsequent poor outcomes in patients with acute ischemic stroke may help in early prognostication and guided therapeutic interventions.

Pineal parenchymal tumor of intermediate differentiation (PPTID) is a rare, primary tumor of the pineal gland. Due to its rarity, there is no consensus on optimal therapeutic strategies or standard characterization of the tumor's behavior. Here, we report 2 new cases of PPTID and an extensive review of the literature involving the use and extent of radiation therapy. Patient 1 is a 54-year-old male who presented with PPTID and drop metastases in the spinal cord, received cranial spinal irradiation (CSI), and experienced recurrence 3.5 years after treatment. Stereotactic body radiation therapy (SBRT) helped the patient into remission for 9 months. Patient 2 is a 32-year-old male with a local PPTID at presentation who went on to receive surgical resection followed by focused adjuvant radiation therapy to the pineal tumor bed. He then presented 6 years after treatment with extensive disseminated recurrence and died due to leptomeningeal disease (LMD) about 4 years after recurrence. The available literature on PPTID is limited and reported cases of LMD with ongoing follow-up in PPTID are scarce. Our report adds to the current known PPTID cases, contributing to the information available regarding prognosis and treatment response. Although an optimal therapeutic strategy for PPTID still cannot be determined, data from the literature suggest that utilizing radiation therapy in patients with low-risk disease and gross total resections as well as the use of upfront CSI have the potential to improve patient progression and survival outcomes.

Background: Mild traumatic brain injury (mTBI) generally resolves within weeks. However, 15-30% of patients present persistent pathological and neurobehavioral sequelae that negatively affect their quality of life. Hyperhomocysteinemia (HHCY) is a neurotoxic condition derived from homocysteine accumulation above 15 μM. HHCY can occur in diverse stressful situations, including those sustained by U.S. active-duty service members on the battlefield or during routine combat practice. Mild-TBI accounts for more than 80% of all TBI cases, and HHCY exists in 5-7% of the general population. We recently reported that moderate HHCY exacerbates mTBI-induced cortical injury pathophysiology, including increased oxidative stress. Several studies have demonstrated hippocampus vulnerability to oxidative stress and its downstream effects on inflammation and cell death.

Objective: This study aimed to assess the deleterious impact of HHCY on mTBI-associated hippocampal pathological changes. We tested the hypothesis that moderate HHCY aggravates mTBI-induced hippocampal pathological changes.

Methods: HHCY was induced in adult male Sprague-Dawley rats with a high methionine dose. Rats were then subjected to mTBI by controlled cortical impact under sustained HHCY. Blood plasma was assessed for homocysteine levels and brain tissue for markers of oxidative stress, blood-brain barrier integrity, and cell death. Endothelial cell ultrastructure was assessed by Electron Microscopy and working memory performance using the Y maze test.

Results: HHCY increased the hippocampal expression of nitrotyrosine in astroglial cells and decreased tight junction protein occludin levels associated with the enlargement of the endothelial cell nucleus. Furthermore, HHCY altered the expression of apoptosis-regulating proteins α-ii spectrin hydrolysis, ERK1/2, and AKT phosphorylation, mirrored by exacerbated mTBI-related hippocampal neuronal loss and working memory deficits.

Conclusion: Our findings indicate that HHCY is an epigenetic factor that modulates mTBI pathological progression in the hippocampus and represents a putative therapeutic target for mitigating such physiological stressors that increase severity.

Background: Nerve cross-sectional area (CSA) reference values in high-resolution ultrasound for children and adolescents are influenced by demographic and anthropometric factors such as age, height and weight.

Objectives: The influence of hand volume as an additional morphometric factor was evaluated and nerve echogenicity was analyzed in a prospective cross-sectional study.

Methods: CSA were measured in 30 healthy children and adolescents from 2 to 17 years in the median, ulnar, radial, tibial, peroneal and sural nerves. Height, weight, age, handedness and gender were recorded, the volume of the hands was measured using the water displacement method. The intra-nerve CSA variability (INV), left/right ratios and absolute differences were calculated. Age groups were compared by the Kruskal-Wallis test. The influence of demographic factors was analyzed using Spearman correlation and multiple linear regression. Echogenicity and fraction of black were determined for each nerve segment.

Results: Nerve CSA values were consistently lower than those reported for adults and correlated in all measured nerve sites with age, height, weight and hand volume. Weight showed the highest correlation coefficient (R = .95) with the best fitting model predicting CSA. Correlation coefficients were higher in a linear than in a logarithmic model. Ratios were stable, the absolute differences increased with age and were significantly different between age groups. Most nerves showed a mixed or hypoechogenic pattern in echogenicity analysis, hyperechogenicity is less frequently observed.

Conclusions: Nerve CSA in children and adolescents is lower than in adults and increases proportionally during growth with a constant INV and left/right ratio in different age groups. Weight and age are predominant anthropometric factors predicting nerve size. Hand volume is correlated with nerve size, but does not predict CSA independently. Echogenicity can provide additional information on nerve structure.

Background: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an uncommon neurological disease affecting the central nervous system (CNS). Numerous neurological disorders, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), acute transverse myelitis (ATM), and MOGAD, have been reported following the COVID-19 infection during the current COVID-19 pandemic. On the other hand, it has been suggested that patients with MOGAD may be at greater risk for infection (particularly in the current pandemic).

Objective: In this systematic review, we gathered separately 1) MOGAD cases following COVID-19 infection as well as 2) clinical course of patients with MOGAD infected with COVID-19 based on case reports/series.

Methods: 329 articles were collected from 4 databases. These articles were conducted from inception to March 1^st, 2022.

Results: Following the screening, exclusion criteria were followed and eventually, 22 studies were included. In 18 studies, a mean ± SD time interval of 18.6 ± 14.9 days was observed between infection with COVID-19 and the onset of MOGAD symptoms. Symptoms were partially or completely recovered in a mean of 67 days of follow-up.Among 4 studies on MOGAD patients, the hospitalization rate was 25%, and 15% of patients were hospitalized in the intensive care unit (ICU).

Conclusion: Our systematic review demonstrated that following COVID-19 infection, there is a rare possibility of contracting MOGAD. Moreover, there is no clear consensus on the susceptibility of MOGAD patients to severe COVID-19. However, obtaining deterministic results requires studies with a larger sample size.

Verteporfin and 5-ALA are used for visualizing malignant tissue components in different body tumors and as photodynamic therapy in treating isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM). Additionally, verteporfin interferes with Yes-associated protein 1 (YAP)/Transcriptional coactivator with PDZ-binding motif - TEA domain (TAZ-TEAD) pathway, thus inhibiting the downstream effect of these oncogenes and reducing the malignant properties of GBM. Animal studies have shown verteporfin to be successful in increasing survival rates, which have led to the conduction of phase 1 and 2 clinical trials to further investigate its efficacy in treating GBM. In this article, we aimed to review the novel mechanism of verteporfin's action, the impact of its interaction with YAP/TAZ-TEAD, its effect on glioblastoma stem cells, and its role in inducing ferroptosis.

Since the original description of Alzheimer´s disease (AD), research into this condition has mainly focused on assessing the alterations to neurons associated with dementia, and those to the circuits in which they are involved. In most of the studies on human brains and in many models of AD, the glial cells accompanying these neurons undergo concomitant alterations that aggravate the course of neurodegeneration. As a result, these changes to neuroglial cells are now included in all the "pathogenic cascades" described in AD. Accordingly, astrogliosis and microgliosis, the main components of neuroinflammation, have been integrated into all the pathogenic theories of this disease, as discussed in this part of the two-part monograph that follows an accompanying article on gliopathogenesis and glioprotection. This initial reflection verified the implication of alterations to the neuroglia in AD, suggesting that these cells may also represent therapeutic targets to prevent neurodegeneration. In this second part of the monograph, we will analyze the possibilities of acting on glial cells to prevent or treat the neurodegeneration that is the hallmark of AD and other pathologies. Evidence of the potential of different pharmacological, non-pharmacological, cell and gene therapies (widely treated) to prevent or treat this disease is now forthcoming, in most cases as adjuncts to other therapies. A comprehensive AD multimodal therapy is proposed in which neuronal and neuroglial pharmacological treatments are jointly considered, as well as the use of new cell and gene therapies and non-pharmacological therapies that tend to slow down the progress of dementia.

Background: Leprosy is primarily a disease of peripheral nerves. Some isolated case reports and case series have communicated imaging changes in the central nervous system (CNS) and brachial plexus in patients with leprosy.

Objectives: To study the neuroimaging abnormalities in patients with lepra bacilli-positive neuropathy in the context of CNS, spinal root ganglion, and brachial plexus.

Design: Prospective observational study.

Methods: We screened newly-diagnosed patients with multibacillary leprosy presenting with neuropathy. Patients with bacilli-positive sural nerve biopsies were included in the study and subjected to magnetic resonance imaging (MRI) of the brain and spinal cord.

Results: A total of 54 patients with bacteriologically confirmed multibacillary leprosy were screened; Mycobacterium leprae was demonstrated in the sural nerve biopsies of 29 patients. Five patients (5/29; 17.24%) had MRI abnormalities in CNS, spinal root ganglion, and/or brachial plexus. Three patients had MRI changes suggestive of either myelitis or ganglionitis. One patient had T2/FLAIR hyperintensity in the middle cerebellar peduncle while 1 had T2/FLAIR hyperintensity in the brachial plexus.

Conclusion: CNS, spinal root ganglion, and brachial plexus are involved in patients with leprous neuropathy. Immunological reaction against M leprae antigen might be a plausible pathogenetic mechanism for brachial plexus and CNS imaging abnormalities.

The high efficacy of natalizumab in the treatment of relapsing-remitting multiple sclerosis (MS) is without controversy. Indeed, effective disease control was not only demonstrated in the pivotal trials but has been corroborated impressively in real-world observations. This monoclonal IgG4 antibody blocks the α4β1 integrin-mediated leukocyte-endothelial interaction and thereby inhibits the migration of immune cells to the brain parenchyma. However, treatment with natalizumab carries the risk of progressive multifocal leukoencephalopathy (PML). This potentially lethal side effect is a significant limitation for treatment initiation and long-term therapy. Natalizumab is given intravenously or subcutaneously in the standard dose of 300 mg every 4 weeks, allowing drug concentrations at levels that ensure continuous α4β1 integrin receptor saturation on the surface of immune cells. Extended-interval dosing (EID) is an emerging treatment approach that aims to mitigate the natalizumab-related PML risk by prolonging the standard infusion intervals to 6 weeks or even more. This treatment approach may abrogate the PML risk due to improved immune surveillance within the central nervous system while maintaining clinical efficacy. Moreover, even an individual interval dosing can be envisioned based on the availability of a biomarker that is capable of monitoring both safety and efficacy aspects. This review summarizes the early and encouraging evidence for EID from observational and randomized-controlled trials and discusses current limitations and upcoming challenges for introducing a tailored treatment approach.