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Pediatric Subarachnoid Hemorrhage: Rare Events with Important Implications

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Research Article

Pediatric Subarachnoid Hemorrhage: Rare Events with Important Implications

  • Abeer Dagra 1*
  • Eric Williams 1
  • Sina Aghili-Mehrizi 1
  • Michael A Goutnik 1
  • Melanie Martinez 1
  • Ryan C Turner 1
  • Brandon Lucke-Wold 1

*Corresponding Author: Abeer Dagra, Division of Gastroenterology, Hepatology and Nutrition, College of Medicine, University of Florida, USA.

Citation: A Dagra, E Williams, Sina A Mehrizi, Michael A Goutnik, M Martinez, et al. (2022). Pediatric Subarachnoid Hemorrhage: Rare Events with Important Implications. J Brain and Neurological Disorders. 5(1); DOI:10.31579/2642-973X/020

Copyright: © 2022, Abeer Dagra, This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received: 01 March 2022 | Accepted: 09 March 2022 | Published: 14 March 2022

Keywords: subarachnoid hemorrhage; aneurysm; SAH management; pediatric population.

Abstract

Rupture of an aneurysm is the leading cause of subarachnoid hemorrhage (SAH) which results in accumulation of blood between the arachnoid and pia mater, consequently increasing intracranial pressure. This often results in life threatening conditions like herniation or clinical presentations including focal neurological deficits. In children, these events, although rare, have significant implications. Pediatric SAH is associated with better outcomes in the hospital setting and may even be prevented proactively by the recognition of potential risk factors. Specifically, better recognition of genetic predispositions, metastatic lesions, and infectious causes of aneurysms is important to understand their growth and prevent hemorrhagic events. This review highlights the causes of pediatric SAH, reviews the models of current understanding of this etiology, and discusses the current treatment schema to provide a succinct summary and highlight gaps in current knowledge. This may lead to future investigations aimed at further improving prevention strategies, patient care, and patient outcomes.

Introduction

Pediatric subarachnoid hemorrhage (pSAH) is a relatively rare clinical event with life-threatening implications that affect 0.5 percent to 4.6 percent of children [[1, 28, 31, 43, 44, 49]]. Aneurysms, arteriovenous malformations, and pediatric tumors are the most common causes of pSAH. Increased predilection is based on genetics or underlying infection. Common symptoms of pSAH include lethargy, irritableness, seizures, increased or decreased muscular tone, altered consciousness, vomiting, poor eating, breathing problems, and apnea [[18]]. Common causes of pSAH include genetic and infectious etiologies that predispose children to develop aneurysms. One of the probable complications of pSAH is brain swelling, or hydrocephalus; this buildup of cerebrospinal fluid (CSF) and blood between the brain and the skull raises the intracranial pressure [29, 58, 62, 63, 75]. In an event of SAH, blood vessels in the brain can become irritated and damaged by the breakdown of blood products (including oxyhemoglobin) leading them to constrict which limits intracerebral blood flow [15, 58, 62]. This could lead to stroke and further exacerbation of the existing injury. Potential consequences of the bleeding include lifelong brain damage, paralysis, or coma in severe circumstances. Given these implications of pSAH, the need for understanding the causation and to plan the management of these events is vital for improved patient outcomes.

Genetics:

Aneurysms in children are thought to be characterized by changes in arterial flow, extracellular matrix, and arterial wall deterioration or repair, all of which may trigger molecular alterations that lead to formation of aneurysms [33, 76]. Genetic and infectious predispositions include: Alagille syndrome,sickle cell anemia,irradiation, cardiac myxoma(Carney complex), HIV/AIDS,tuberous sclerosis, vascular anomalies, Marfan syndrome, syphilis, Moya Moya disease, pseudoxanthoma elasticum, type IV Ehlers-Danlos syndrome, fibromuscular dysplasia, von Hippel-Lindau syndrome, arterio-venous malformations secondary to Osler-Weber-RenduSyndrome, hypertension, coarctation of the aorta and polycystic kidney disease. [13, 31, 76] (summarized in Table 1). In addition, compared to the adult population, mycotic aneurysms make up a greater fraction of aneurysms (4%) in the pediatric population [5, 28]. In immunocompetent individuals, Staphylococcus aureus and Streptococcus are the causal organisms, while in immunocompromised patients, Aspergillus, Candida, and Phycomycetes are the causative organisms [3, 31,76].

Although uncommon, pSAH secondary to neoplasms has been recorded in 3-10% of cases, with medulloblastoma (malignant), primitive neuroectodermal tumors, malignant astrocytomas, and ependymomas being the most prevalent [24, 72]. Possible disruption of tumor vasculature due to the increasing tumor size, direct tumor infiltration of vessels, and/or aberrant tumor vascularity are some of the theorizedmechanisms for aneurysm development and rupture [72].

 

 

 

EtiologyDescriptionGenetic mutationReferences
Alagille syndromeChroniccholestasis due to a lack of intrahepatic bile ducts, congenital heart disease primarily affecting the pulmonary outflow tract and vasculature, butterfly vertebrae, a broad forehead, posterior embryotoxic and/or anterior segment abnormalities of the eyes, and pigmentary retinopathy are among the main clinical features and malformations of this autosomal dominant defect. Intracranial hemorrhage and renal dysplasia are two prominent characteristics.

JAG1

NOTCH2 mutation (rare cases)

[58,65, 76]
Sicklecell anemia

This autosomal recessive genetic disorder causes sickle-shaped red blood cells that are sticky and defective, resulting in ischemia. Despite the fact that cerebral infarctions are more common, aneurysm growthcontributes to

SAH in thepopulation.

HBB gene on chromosome

11

[59,61]
CarneyComplexMyxomasthat begin in childhood and reoccur, causing disruptive cardiac outflow, embolic, and aneurysmal problems that contribute to stroke, are all symptoms of this autosomal dominant pattern disorder.

PRKAR1A/2p16 and 17q22–

24 (unknown gene)

[59,67]
Sturge-Weber SyndromeCauses the growth of aberrant blood vessels in a child's face, brain, or both. Venous congestion is thought to be a key cause of SAH and ICH in this population. Majority of children are born with a mark on their face termed a capillary malformation or port wine stain.

GNAQgene on

chromosome 9q21

[40,45, 59]

Tuberous

Sclerosis

Mentalretardation, epilepsy, and adenoma sebaceum are the classic triad of this autosomal dominant defect.Multiple intracranial aneurysms and kidney cysts are associated with it.TSC1 on chromosome 9 and TSC2 on chromosome 16[40,59]

vascular

anomalies

The inability to repair or maintain vascular integrity, as well as the presence of less stable versions of normal anatomy that are prone to aneurysm formation.Secondary to various congenital diseases[40,59]
MarfansyndromeAneurysms and hemorrhagic strokes are among the neurovascular consequences of this autosomal dominant musculoskeletal disorder.

Fibrillin-1 on chromosome

15

[40,59]

MoyaMoya

Disease(MMD)

Autosomal dominant inheritance disease with thickened intima of major branches of the circle of Willis and Moya Moya arteries as a general finding. In individuals with MMD, intracerebral hemorrhage is a commoncause of mortality.

Mutations in chromosome

3p24.2–26, and 17q

[10, 23, 35, 59]

Pseudoxanthoma

elasticum

An autosomal dominant and recessive inheritance condition that generates cerebral and cardiovascular aneurysms.ABCC6/16p13.1[59]

Type IV Ehlers-

Danlossyndrome

Ehlers-Danlos syndrome is characterized by hyperplastic skin and hyperextensible joints due to an autosomal dominant collagen synthesis deficiency. Furthermore, Ehlers-Danlos vascular type IV is associated with spontaneous rupture of arteries, including intracranial arteries.typeIII procollagen (COL3A1) on chromosome 2q[40,59]

von Hippel-

Lindau Syndrome (VHL)

Throughthe activities of transcription factors, growth factors, and matrix metalloproteinases, the VHL tumor suppressor gene may be causally linked to aneurysm formation, resulting to SAH in some cases.

Although hemangioblastomas in VHL arenoninvasive, their increasing size can compress tissue and disrupt blood flow or they may hemorrhage, resulting in the observed clinical symptoms.

VHL gene on chromosome 3[8, 12, 59]

Osler-Weber-

Rendu Syndrome or Hereditary Hemorrhagic Telangiectasia (HHT)

Telangiectasias of the skinand mucosal membranes, as well as arteriovenous abnormalities in internal organs, contribute to hemorrhagic strokes.

Endoglin (ENG)/9q33–q34.1

and ALK1or ACVRL1/12q11– q14

[59]

Autosomal

Dominant Polycystic Kidney Disease (ADPKD)

Intracerebral aneurysms caused by

ADPKD are uncommon in children, but they are highly influenced by family history. Documented prevalence rates range from 0% to 41%.

PKD1 gene on chromosome 16 PKD2 gene on chromosome 4[19, 40, 48, 55, 59, 69]

Table 1: Genetic Predispositions of Pediatric Subarachnoid hemorrhage

Vascular abnormalities:

Pediatric aneurysms differ from classical adult aneurysms; they are rarer, tend to be larger, have an overall male predominance, are commonly caused by infection or trauma, and have increased predilection for the posterior circulation [28, 31, 44, 50, 52, 70]. Additionally, aneurysmsin children tend to be associated with congenital disorders [3, 5, 13, 31, 40, 44, 47, 50, 66] (table 1).

Intracranial aneurysms may present in children commonly 2-4 weeks (but up to 10 years) following trauma, usually a closed head injury (72% of cases) and may present with massive epistaxis [26, 57]. Traumatic brain injury may damage the distal anterior carotid artery (ACA) in40% of cases, the major vessels along the skull base in 35% of cases, and the distal cortical vessels in 25% of cases [37]. The patient presents with hemorrhage in about 50

Treatment

Pediatric SAH may be treated effectively by either microsurgery or endovascular techniques such as coil embolization whereby an aneurysm is stabilized to prevent rupture by placing a coil that prevents enlarging of false lumen [30, 42, 50, 54, 56, 59, 60, 71]. Choice of procedure may be decided based on location, Hunt and Hess grade, complex shape, amenability to coiling, vessel occlusion probability, and parental choice [50, 56, 60, 71]. The decision should not be influenced by aneurysm size [60].Depending on the preferences of the institution, endovascular approaches may be employed for specific anatomic locations, such as the basilar trunk and posterior cerebral artery (PCA) [56]. Surgical excision remains the treatment of choice for parenchymal AVMs in children [36, 53, 74], with complete removal achieved in most patients (up to 90%). Complete AVM resectionusually results in normalneurological outcome [36].

Treatment options also include endovascular embolization and stereotactic radiosurgery alone or in combination. The Spetzler-Martin (SM) grading scale, which estimates the risk for patient with undergoing neurosurgery by evaluating the AVM size, location, and pattern of venous flow, is often used to determine the treatment modality, with low grade, accessible SM grade 1-3 AVMs being best managed with surgery, while low grade inaccessible AVMs are best treated with stereotactic radiosurgery. High grade (SM grade 4-5) AVMs in pediatric patients are often deep or inaccessible making surgical excision less possible. The best treatment modality for these AVMs is unclear [53]. Conservative management for children with AVMs is generally not recommended, with anannual risk of rupture increasing by 2-4% per year [14, 36, 37,53, 74].

Aggressive management is likely to result in superior clinical outcomes in pediatric patients [36, 37, 53, 74]. Moreover, Stiefel et al. suggested that surgical intervention may be first line, but coil embolization is preferred when surgery is not viable, or the aneurysm is located at the basilar apex [50]. Long-term follow up studiesare needed to compare the durability of coiling comparedto standard microsurgical clipping because of better outcomes in children contributing to longer survival. Thus, comparing the modalities in preventing future hemorrhage is a uniquely important consideration in the pediatric population [50, 71].

Pediatric patients are more likely to have favorable post-surgical outcomes, compared to adults [68]. Favorable outcomes range from approximately 63.6% to 90

Conclusion

SAH is associated with trauma, infection, and vascular abnormalities in the pediatric population, and it requires high levels of care during management and after discharge. However, whenidentified in a timely manner, the outcomes for patients with pSAH are more favorable in this population. Specifically, preventing rebleeding and vasospasms, using pharmacotherapy to improve blood flow, and closely monitoring symptoms and vitals help prevent neurologic and hemodynamic complications. Patients who may develop such complications may require extended hospital stay, additional surgeries, and therapies like Triple-H. Many SAH survivors may develop chronically disabling medical disorders, including issues with mood, neurophysiological function, and memory. For populations with predisposing genetic conditions that affect vasculature (e.g. AVM formations), early monitoring may be an effective preventative measure for these acute events. Moreover, closing the knowledge gap on epidemiological and biochemical predisposition to aneurysmal growth and rupture will inspire better preventive, management, and treatment protocols for pSAH.

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Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.

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Virginia E. Koenig

Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.

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Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.

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Mina Sherif Soliman Georgy

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Orlando Villarreal

Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.

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Pedro Marques Gomes

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Hao Jiang

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Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.

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Andreas Filippaios

Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.

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I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!

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Baheci Selen

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Jesus Simal-Gandara

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Douglas Miyazaki

We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.

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Dr Griffith

I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.

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I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.

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Husain Taha Radhi

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S Munshi

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George Varvatsoulias

Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.

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Rui Tao

Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.

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Khurram Arshad

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Gomez Barriga Maria Dolores

The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.

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Lin Shaw Chin

Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.

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Maria Dolores Gomez Barriga

Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.

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Dr Maria Dolores Gomez Barriga

Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.

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Dr Maria Regina Penchyna Nieto

Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.

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Dr Marcelo Flavio Gomes Jardim Filho

Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”

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Zsuzsanna Bene

Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner

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Dr Susan Weiner