Neutrophil-Mediated Immunopathology and Matrix Metalloproteinases in Central Nervous System – Tuberculosis

Tuberculosis (TB) remains one of the leading infectious killers in the world, infecting approximately a quarter of the world’s population with the causative organism Mycobacterium tuberculosis (M. tb). Central nervous system tuberculosis (CNS-TB) is the most severe form of TB, with high mortality and residual neurological sequelae even with effective TB treatment. In CNS-TB, recruited neutrophils infiltrate into the brain to carry out its antimicrobial functions of degranulation, phagocytosis and NETosis. However, neutrophils also mediate inflammation, tissue destruction and immunopathology in the CNS. Neutrophils release key mediators including matrix metalloproteinase (MMPs) which degrade brain extracellular matrix (ECM), tumor necrosis factor (TNF)-α which may drive inflammation, reactive oxygen species (ROS) that drive cellular necrosis and neutrophil extracellular traps (NETs), interacting with platelets to form thrombi that may lead to ischemic stroke. Host-directed therapies (HDTs) targeting these key mediators are potentially exciting, but currently remain of unproven effectiveness. This article reviews the key role of neutrophils and neutrophil-derived mediators in driving CNS-TB immunopathology.

The Dermal Sinus: About 29 Cases and Review of the Literature

The term spina includes several types of congenital malformations including closed spinal dysraphisms, among these 10% are dermal sinuses.Our series includes 29 patients, the majority of which were asymptomatic, but these can present with different clinical pictures including neurological and / or infectious signs indicating a neglected dermal sinus and which therefore requires urgent treatment in the environment. Neurosurgical.MRI confirmed the diagnosis showing the dermal sinus tract communicating from the surface of the skin to the intra-dural space.Once the diagnosis has been made, surgical treatment becomes imperative and urgent because, despite the benignity of the lesion, the majority of which are located in the lumbar region, can lead to formidable neurological sequelae compromising the functional prognosis or even the vital prognosis in some cases.All of our patients were operated on and we obtained 90% good results, however we deplore one case of aggravation and one death.

Neurological Sequela of Acute Pesticide Poisoning Among Adults in Central Taiwan

Background and Purpose: Cases of acute pesticide poisoning account for significant morbidity and mortality in developing countries; however, its burden in Taiwan remains unknown. The study examined acute pesticide poisoning (APP) involving adults in the central region of Taiwan, which is a mainly agricultural sub-urban area.Methods: The retrospective study evaluated the outcome and neurological sequelae of patients with APP in a Taiwanese cohort between April 2002 and February 2019. The pesticides were classified according to the Insecticide Resistance Action Committee Mode of Action (MoA) classification. The clinical characteristics, duration of hospitalization (days), follow-up duration (years), in-hospital mortality, neurological sequela, and imaging findings were recorded. Furthermore, multivariate logistic regression analyses were performed.Results: We identified 299 patients with APP comprising 206 (68.9%) adult men with a mean exposure age of 56.4 ± 16.8 years. Paraquat, organophosphates, pyrethroids, carmabates, and phosphinic acid were the most commonly known reported poisoning agents. The mortality rate was highest in users with paraquat (77.1%), followed by phosphinic acid (22.2%), carbamates (16.7%), and organophosphates (15.8%). After a mean follows up of 3.69 ± 2.26 years, the most common neurological sequela was a cognitive decline (56 among 225 survivors, 24.89%), peripheral neuropathy (11 among 225 survivors, 4.89%), tremor (10 among 225 survivors, 4.44%), ataxia (3/225, 1.33%), and parkinsonism feature (2/225, 0.89%). Brain imaging studies revealed basal ganglion lesions on CT or hyperintensity on T2-weighted MRI images in 26 among 46 patients (56.5%). The basal ganglion lesions on brain imaging had a positive correlation with neurological sequelae.Conclusion: Acute pesticide poisoning (APP)-related mortality is high especially paraquat intoxication, and cognitive decline, as well as peripheral neuropathy, were the most common neurological sequelae among survivors, which is highly correlated with basal ganglia lesions on brain imaging.

Management of Lambdoid Craniosynostosis: A Comprehensive and Systematic Review

<b><i>Background:</i></b> Craniosynostosis is a condition characterized by the premature fusion of 2 or more skull bones. Craniosynostosis of the lambdoid suture is one of the rarest forms, accounting for 1–4% of all craniosynostoses. Documented cases are separated into simple (single suture), complex (bilateral), and associated with adjacent synostoses (“Mercedes Benz” Pattern) or syndromes (i.e., Crouzon, Sathre-Chotzen, Antley-Bixler). This condition can manifest phenotypic deformities and neurological sequelae that can lead to impaired cognitive function if improperly treated or left undiagnosed. Preferred surgical techniques have varied over time but all maintain the common goals of establishing proper head shape and preventing of complications that could contribute to aforementioned sequelae. <b><i>Summary:</i></b> This comprehensive review highlights demographic distributions, embryological development, pathogenesis, clinical presentation, neurological sequelae, radiologic findings, surgical techniques, surgical outcomes, and postoperative considerations of patients with lambdoid craniosynostosis presentation. In addition, a systematic review was conducted to explore the operative management of lambdoid craniosynostosis using PubMed, Embase, and Scopus databases, with 38 articles included after screening. <b><i>Key Messages:</i></b> Due to a low volume of published cases, diagnosis and treatment can vary. Large overlap in presentation can occur in patients that display lambdoid craniosynostosis and posterior plagiocephaly, furthering the need for comprehensive analysis. Possessing the knowledge and tools to properly assess patients with lambdoid craniosynostosis will allow for more precise care and improved outcomes.

Damage control surgery for grade IV blunt hepatic injury with multiple organ damage in a child: a case report

Background Intra-abdominal hemorrhage caused by blunt hepatic injury is a major cause of morbidity and mortality in patients with abdominal trauma. Some of these patients require laparotomy, and rapid decision-making and life-saving surgery are essential. Damage control (DC) surgery is useful for treating children in critical situations. We performed this technique to treat an 8-year-old boy with grade IV blunt hepatic injury and multiple organ damage. This is the first report of the use of the ABTHERA Open Abdomen Negative Pressure Therapy System (KCI, now part of 3 M Company, San Antonio, TX, USA) for DC surgery to rescue a patient without neurological sequelae. Case presentation An 8-year-old boy was brought to the emergency department of our hospital after being run over by a motor vehicle. He had grade IV blunt hepatic injury, thyroid injury, and bilateral hemopneumothorax. Although he was hemodynamically stable, the patient’s altered level of consciousness, the presence of a sign of peritoneal irritation, and suspicion of intestinal injury led us to perform exploratory laparotomy. As part of a DC strategy, we performed gauze packing to control hemorrhage from the liver and covered the abdomen with an ABTHERA Open Abdomen Negative Pressure Therapy System to improve the patient’s general condition. Eighteen days after admission, the patient was diagnosed with a biliary fistula, which improved with percutaneous and external drainage. He had no neurological sequelae and was discharged 102 days after injury. Conclusion The DC strategy was effective in children with severe blunt hepatic injury. We opted to perform DC surgery because children have less hemodynamic reserve than adults, and we believe that using this strategy before the appearance of trauma triad of death could save lives and improve outcomes. During conservative management, it is important to adopt a multistage, flexible approach to achieve a good outcome.

Dementia with non-convulsive seizures: a case report

Non-convulsive seizures (NCSs) are highly treatable, but appropriate management is usually delayed because of inaccurate diagnoses as a result of variable clinical presentations, including an altered mental state. It is difficult to detect NCSs in patients with dementia. We report a case of NCS superimposed on cognitive decline caused by Alzheimer’s dementia. The patient’s history was carefully recorded. An electroencephalogram was recorded with sphenoidal electrodes, which showed epileptiform discharges in the right mesial temporal lobe and focal, sharply contoured, slow wave activity in the left fronto-temporal area, suggesting an epileptic origin contributing to the patient’s cognitive decline. After treatment with antiepileptic drugs, the patient’s cognitive functioning gradually improved. An accurate diagnosis of NCS relies on performing a detailed inventory of a patient’s history, thorough physical and neurological examinations, and electroencephalogram recordings. In patients with cognitive decline, testing for NCS should always be included in the differential diagnosis of cognitive impairment, even in the case of dementia. Early administration of antiepileptic drug therapy is the mainstay treatment for reversing the condition and for preventing prolonged insults from neurological sequelae.

Immunoglobulin-Induced Aseptic Meningitis in Juvenile Dermatomyositis: A Case Report

Background: Aseptic meningitis is a known but unusual serious adverse effect of intravenous immunoglobulin (IVIG). It usually resembles infectious meningitis which makes diagnosis challenging. Case presentation: We report a five-and-a-half-year-old Chinese girl with juvenile dermatomyositis presented with signs of meningismus 21 hours after the initiation of IVIG infusion. Her blood work at diagnosis showed neutrophilia and lymphopenia. The cerebrospinal fluid analysis demonstrated neutrophilic pleocytosis, hyperproteinorrachia and normoglycorrhachia. All microbiological tests were negative. The child recovered fully within 72hours without neurological sequelae.Conclusion: IVIG-induced aseptic meningitis remains a diagnosis of exclusion. Although it is rare, paediatricians should be aware of this complication and avoid unnecessary investigation or treatment.

Treatment Goals for Achondroplasia: A Qualitative Study with Parents and Adults

Background: Achondroplasia is characterized by disproportionate short stature accompanied by other changes to the musculoskeletal system. Individuals with this condition typically experience a variety of medical complications. Pharmacologic treatments are being developed for the treatment of achondroplasia. It is important to understand the goals for pharmacologic treatment among those affected by achondroplasia and factors that shape these views. Methods: This qualitative study is based on semi-structured interviews with 19 parents of children with achondroplasia and 5 adults with achondroplasia in the United States. We employed thematic analysis using an iterative process to identify themes across the interviews. Results:Participants had two goals for pharmacologic treatment of achondroplasia: ameliorating complications associated with the condition and increasing stature to overcome functional limitations and psychosocial challenges. Complications of particular concern were chronic pain and surgeries to repair spinal, ENT, and neurological sequelae. Increased height would enhance independence, fitting in socially, and avoiding social stigma. Despite many challenges, parents and adults with achondroplasia expressed that they found ways to adapt and emphasized satisfaction and the positive aspects of their lives. Concerns about medical treatment included fear of loss of their identity as a little person. Conclusions:This study offers evidence about how individuals affected by achondroplasia think about pharmacologic treatment of this condition, including both the benefits of ameliorating complications and increasing height. The findings can offer practical insights for parents of children considering treatment, treating physicians and decision makers evaluating coverage decisions for treatment of achondroplasia.