Patient Presentation
A 4-year-old female came to the emergency room with a history of increased seizures for the past several days. She was a former premature infant with hypoxic-ischemic encephalopathy who had known intermittent seizures that were usually treated with levetiracetam. She had been more tired, cranky and had had 3 seizures in 3 days. She did not need rescue medication, and had had her usual post-ictal somnolence for about 1-2 hours each time. Her parents thought she was worsening overall and brought her to the emergency room. She had fallen during a playground game 5 days previously and hit her head on the cement. She was not able to participate in school for the rest of the day but did go to school for the rest of the week. Her medications had not recently changed and her parents were adamant that she had received her regular dosing on schedule and had not seen any evidence of medication poisoning.

The review of systems was negative for fever, diarrhea, rashes and upper respiratory symptoms. She did complain that her head hurt and the lights in the emergency room hurt her eyes and these were new symptoms per the parents.

The pertinent physical exam her heart rate was 62 beats/minute, blood pressure was 115/60, respiratory rate of 24. Her Glascow coma scale was 15 but she appeared very tired. She would become cranky easily during the examination, especially the eye examination which could not be completed. Her overall examination was normal and there were no specific focal findings on neurological examination.

The work-up included the usual laboratory evaluation and urine for toxicology. The radiologic evaluation of computed tomography revealed a brainstem mass. Magnetic resonance imaging was most consistent with glioma. The patient’s clinical course showed that stereotactic biopsy was planned for further evaluation of the mass. The diagnosis of pediatric-type diffuse high-grade glioma was eventually made and radiation was started. Chemotherapy was also being considered.

Figure 150 – Sagittal T1 MRI without contrast of the brain (above left) shows a large mass expanding the entire brainstem. Axial T2 (above right) and axial FLAIR (below left) MRI show the mass to be somewhat heterogenous and the mass has multiple foci of enhancement on the axial T1 MRI with contrast (below right).

Discussion
Brain tumors, even those with favorable prognoses, have the potential for causing morbidity and mortality within a short-time because of their obvious space-occupying capacity within the closed space of the skull. Secondary brain tumors, those due to metastases from distant location cancers, are the most common brain tumors.

Risk factors for gliomas include age and exposure to ionizing radiation. “Cellular phone use is not associated with increased risk of gliomas.” Hereditary risk factors for gliomas are well known for some genetic mutations. Family history is positive for 5% of glioma patients without a known tumor predisposition syndrome such as the following:

• Neurofibromatosis type 1 – especially pilocytic astrocytoma (Grade 1)
• Neurofibromatosis type 2 – especially spinal ependymoma
• Tuberous sclerosis complex – subependymal giant cell astrocytoma
• Li-Fraumeni syndrome – several cancers including IDH-wild-type- high-grade astrocytic gliomas or IDH-mutant astrocytomas
• Lynch syndrome – IDH-mutant astrocytomas

Presentation usually is due to evaluation for focal neurological deficits, seizures, and increasing/non-resolving symptoms such as headache. They can also be an incidental finding such as neuroimaging after head trauma, or may be found due to screening for patients with hereditary cancer syndromes. Magnetic resonance imaging or Positron emission tomography (PET) scans are usually the imaging of choice. Treatment is primary surgical if the tumor is amenable. Radiation and chemotherapy can be options in some cases. Management of other problems such as cerebral edema by use of dexamethasone, anti-epileptics, and multi-disciplinary management with physical therapy, speech therapy, occupational therapy, social work and psychology can also be important for overall functioning. Quality of life can be dramatically altered even with a “treatable” glioma. Patients have increased risk of mental health issues such as depression and anxiety, fatigue, and continued seizures. Survivors can also have neurocognitive impairment (including cognition, attention, processing speed, and working memory), psychosocial problems and overall lower socioeconomic status.

Learning Point
Of primary brain tumors in adults and children, 30% are caused by gliomas and 80% of malignant brain tumors are caused by gliomas. Overall central nervous system (CNS) tumors have an incidence of 24.83/100,000 population, occurring in females more than males and also more in non-Hispanic populations. The highest incidence is Europe.

Overall the most common brain tumors for adults and children are:

• Meningiomas – 40.8%
• Pituitary tumors – 17.2%
• Glioblastoma – 14.2%
• Nerve sheath tumors – 8.3%
• Diffuse and anaplastic astrocytoma – 3.1%
• Ependymal tumors – 1.5%
• Olidgodendrogliomas and oligoastrocytic tumors 1.3%

The World Health Organization (WHO) 5 major grouping of gliomas are:

• Pediatric-type diffuse low-grade glioma – most common pediatric brain tumor, accounting for 30% of all pediatric brain tumors
• Pediatric-type diffuse high-grade glioma
• Adult-type diffuse glioma – 90% of gliomas overall in adults and children
• Circumscribed astrocytic glioma
• Ependymal tumors

Adult-type gliomas can be found in the pediatric age group and pediatric-type gliomas can be found in the adult age group, especially in the “cross-over” years of young adulthood.

Grading of gliomas

• Grade 1
  • Slow-growing, well-demarcated, usually amenable to surgery, favorable prognosis
  • Example: pilocytic astrocytoma
• Grade 2
  • Slow-growing, have invasive growth so not amenable to complete resection
  • Example: diffuse astrocytoma and oligodendrogliomas
• Grade 3
  • Rapidly growing, aggressive growth
  • Example: anaplastic astrocytomas and oligodendrogliomas
• Grade 4
  • Rapidly growing, highly aggressive, poor prognosis
  • Example: glioblastoma, IDH wild type, pediatric-type high grade

Overall prognosis depends on the group, grade, specific molecular subtypes and location.

Questions for Further Discussion
1. What are the components of Cushing’s triad?
2. What is the scoring system for the Glascow Coma Scale? A review can be found here
3. What is in the differential diagnosis for first time seizures?

Related Cases

Disease: Glioma | Childhood Brain Tumors

Symptom/Presentation: Fatigue | Seizures

Specialty: Neurology / Neurosurgery | Oncology | Radiology / Nuclear Medicine / Radiation Oncology

Age: Preschooler

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews. Information prescriptions for patients can be found at MedlinePlus for this topic: Childhood Brain Tumors

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Sait SF, Giantini-Larsen AM, Tringale KR, Souweidane MM, Karajannis MA. Treatment of pediatric low-grade gliomas. Curr Neurol Neurosci Rep. 2023;23(4):185-199. doi:10.1007/s11910-023-01257-3

Wu J, Heidelberg RE, Gajjar A. Adolescents and Young Adults with Cancer. J Clin Oncol. 2024;42(6):686-695. doi:10.1200/JCO.23.01747

Fangusaro J, Jones DT, Packer RJ, et al. Pediatric low-grade glioma: State-of-the-art and ongoing challenges. Neuro Oncol. 2023;26(1):25-37. doi:10.1093/neuonc/noad195

Weller M, Wen PY, Chang SM, et al. Glioma. Nat Rev Dis Primers. 2024;10(1):33. doi:10.1038/s41572-024-00516-y

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa

Patient Presentation
A 9-year-old male came to clinic for his health maintenance examination. He was overall healthy and there were no parental concerns. The past medical history found him to be fully immunized including seasonal vaccines.

The pertinent physical exam revealed him to have normal vital signs and growth parameters that were 10-50%. His examination was normal.

The diagnosis of a healthy male was made. His mother consented to all vaccines but asked why the HPV vaccine was being done at this age as her older daughter had it at 11-12 years. “In our community the vaccine rate was relatively poor. Not in our clinic but in the community. So we as a practice are following the recommendation to start vaccinating at age 9 years. We had a good rate before but now our rates are even higher so we are happy with the results. For some families who might be hesitant it also gives them a little bit more time to learn about the cancers it prevents and become more comfortable with getting the vaccine. Families like it that we can give it with other vaccines too like flu shots,” he responded.

Discussion
Human papilloma virus (HPV) is a circular, double-stranded DNA-virus that is the most common sexually-transmitted infection in the US and in many places world-wide. Diseases range from genital warts to respiratory papillomatosis to cancer. Cancer locations include skin, oropharyngeal, vulvar, vaginal, cervical, anal and penile cancers. It is estimated that HPV infection is associated with ~125,000 cases of cancer annually in the US.

HPV vaccine was initially approved in 2006 in the US with a quadrivalent vaccine. In 2016 a nonavalent vaccine was approved and is the only HPV vaccine currently approved in the US. The vaccine is recommended for ages to be given at 9-14 years with catchup vaccination routinely done up to 26 years, and potentially as late as 45 years of age with shared decision making between patients and health care providers.

Serotypes included are 6 and 11 (rarely carcinogenic but associated with 90% of anogenital warts and recurrent respiratory papillomatosis), 16 and 18 (associated with 70% of cervical cancers, 16 is associated with 95% of HPV-related oropharyngeal cancers), and 31, 33, 45 and 52 (associated with an additional 20% of cervical cancers). HPV prophylactic vaccines work by blocking entry of the virus into cells, presumably by antibody neutralization.

Learning Point
HPV vaccines are highly efficacious with mild side effects. It is estimated that up to 90% of HPV-related cancers are prevented especially cervical cancer. “Studies have […] demonstrated that earlier administration of the vaccines results in greater immunogenicity and long-lasting protection.” Greater effectiveness “”[…] is likely due to administration of these prophylactic vaccines prior to natural exposure to HPV from sexual activity rather than a biological mechanism independent of natural exposure.” It is estimated that up to 60% of adolescents have their sexual debut by age 18 years. It is also estimated that that “most sexually active women and men will become infected with HPV at least once in their lifetime.” Administration at early ages can lead to greater completion of the vaccine series as well.

Older adolescents and adults do have robust antibody responses that are higher than natural infection which likely gives substantial protection against HPV.

Some studies have also reported herd immunity protection effects as well. As the HPV vaccine has been efficacious, especially against cervical cancer, oropharyngeal cancers still are increasing and are now the main type of HPV-related immunity.

HPV vaccines for treatment (as opposed to prophylaxis) are also being developed designed to induce cellular immunity against established infections and potentially prevent continuation to cancer.

Questions for Further Discussion
1. What are treatments for respiratory papillomatosis? A review can be found here
2. What are treatments for genital warts? A review can be found here
3. What are some methods for counseling families who may be vaccine hesitant? A review can be found here

Related Cases

Disease: HPV | Sexually Transmitted Diseases | Childhood Immunization

Symptom/Presentation: Health Maintenance and Disease Prevention

Specialty: General Pediatrics | Infectious Diseases

Age: School Ager

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews. Information prescriptions for patients can be found at MedlinePlus for these topics: HPV and Vaccines.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Ellingson MK, Sheikha H, Nyhan K, Oliveira CR, Niccolai LM. Human papillomavirus vaccine effectiveness by age at vaccination: A systematic review. Hum Vaccin Immunother. 19(2):2239085. doi:10.1080/21645515.2023.2239085

Skolnik JM, Morrow MP. Vaccines for HPV-associated diseases. Molecular Aspects of Medicine. 2023;94:101224. doi:10.1016/j.mam.2023.101224

Escoffery C, Petagna C, Agnone C, et al. A systematic review of interventions to promote HPV vaccination globally. BMC Public Health. 2023;23(1):1262. doi:10.1186/s12889-023-15876-5

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa

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Patient Presentation
A 13-year-old male came to clinic with a history of bruising. He had been seen in an urgent care 1 month previously where they documented three 2-4 mm bruises and one that was about 8-10 mm on the left side of the abdomen that were just below the umbilicus. The family had noticed them and thought it was unusual so they sought medical care. The history at the time was negative and the laboratory evaluation including a complete blood count, platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen, von Willebrand Factor antigen, and Factor VIII were eventually normal. The family was instructed to see their general pediatrician if the bruises returned. The patient had new bruising of 1 day duration, that occurred on the abdomen again and upper outer right thigh. The patient denied any other bleeding including no bleeding with brushing teeth, epistaxis, or hematochezia. He ate a general diet and the family denied any medication history (except ibuprofen 3 days ago for a headache that resolved) or supplements, herbal products or teas. The family denied obvious trauma. The patient during a private interview also denied any trauma and stated that he felt safe at home and school. The answers given were detailed and interactions with the family and patient seemed appropriate to the examiner.

The past medical history was positive for intermittent bruising normal for daily life including shin or lower arm bruising. He had no problems clotting after a cut and cuts/bruises seemed to heal as usual. The family history was also negative for bleeding problems except for the mother who needed a blood transfusion after birth of a sibling. She had no bruising or other bleeding problems herself. The review of systems was negative.

The pertinent physical exam showed a well-appearing male with normal vital signs and growth parameters. His general examination was normal including all mucous membranes. His skin showed one 5 mm bruise in the right lower abdomen and a 6 cm roundish bruise on the high right upper thigh near the hip. Both were brown/black and appeared to be about the same stage of healing. There was no obvious petechiae.

The diagnosis of abnormal bruising was made. Additional history revealed that the boy did carry a backpack that he did use the belt clip for. He also wore different belts with different belt buckles. The examiner did not feel that this was inflicted trauma and thought that although this could be unrecognized trauma from the backpack or belt buckles, that this possibly could be an unrecognized platelet or bleeding factor problem. The hematologist by telephone consultation agreed and asked that some labs be repeated (i.e. complete blood count with platelets, PT, PTT, fibrinogen, complete metabolic profile, uric acid, lactate dehydrogenase) but wanted to wait on other labs until they saw the patient. The repeated labs were normal and the patient was awaiting the consultation at 2 week followup.

Discussion
Bruising is a common question asked by families. The toddler and young child who is playing and commonly falling will have bruises on the shins which may worry the family. Other places where a person will have bruises or even abrasions or cuts will be prominences such as the hands, elbows, knees, nose, forehead and occiput of the skull. Bruising in places where it would be expected to try to mitigate a fall are also common such as the outside of the arm or shoulder. Bruising on the spine prominences may also be because of a fall or trying to mitigate one. Injuries may be not recognized such as a bruise on the upper thigh, hip or lower abdomen from hitting the corner of a counter/table with bruise’s placement depending on the height of the individual. A stick could poke someone in the abdomen who didn’t recognize it as they were doing yardwork. Bruises could be the first sign of an underlying problem too such as idiopathic thrombocytopenic purpura or cancer.

Non-accidental trauma is always a potential concern and the age of the child along with the area of the bruising can give clues. Non-mobile children are less susceptible to trauma overall. For any person injuries that appear patterned, clustered or in areas where they are likely to be grabbed or hit such as top of head, face, ears, arms and upper legs are more concerning. Additional injuries such as oral or genital injuries or any head trauma also are more concerning for non-accidental trauma.

The history and physical examination of a patient with a history of abdominal or easy bruising is very important and helps to direct the evaluation. Questions about the personal and family history of bruising or bleeding, along with medications and supplements that are consumed and overall dietary history can be very helpful. Of course many questions need to be asked about potential accidental or non-accidental trauma. Less common problems and those that are qualitative problems may be more difficult to identify and often need specialty consultation.

Potential causes of bruising include:

• Trauma
  • Accidental
    • Witnessed
    • Non-witnessed/unrecognized
  • Non-accidental/inflicted/abuse
    • Clustered or patterned bruising
    • Bruising on areas not commonly occurring – back, head, thighs
• Platelet
  • Thrombocytopenia
  • Function problem
• Clotting factors
  • Deficiency
  • Function problem
• Vitamin K deficiency
• Medications **
  • Anti-platelet including aspirin
  • Non-steroidal anti-inflammatory agents
  • Anti-coagulants including heparin and coumadin
• Supplements **
  • Vitamin E
  • Garlic
  • Gingko biloba
• Cancer and infiltrative disease
• Connective tissue integrity/fragility
  • Arteriovenous malformations
  • Ehlers-Danlos syndrome
  • Glutaric aciduria
  • Osteogenesis imperfecta
  • Vitamin C deficiency (scurvy)

** A list of common medications and supplements that can cause bleeding or bruising can be found here.

Learning Point
Initial laboratory evaluation can include:

• Complete blood count with platelet count
• Prothrombin time
• Activated Partial thromboplastin time
• von Willebrand Factor antigen
• von Willebrand Factor activity (Ristocetin cofactor)
• Factor VIII
• Factor IX
• Fibrinogen

D-dimer is also sometimes added. Other laboratory evaluations may also include general screening testing such as a complete metabolic profile, uric acid and lactate dehydrogenase.

Questions for Further Discussion
1. List common congenital platelet problems. A review can be found here and here
2. What are the different types of von Willebrand disease? A review can be found here
3. What are some of the presentations of non-accidental trauma and neglect? A review can be found here

Related Cases

Disease: Bruises

Symptom/Presentation: Bleeding and Bruising

Specialty: Hematology

Age: Teenager

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews. Information prescriptions for patients can be found at MedlinePlus for this topic: Bruises

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Akintoye SO, Mupparapu M. Clinical Evaluation and Anatomic Variation of the Oral Cavity. Dermatologic Clinics. 2020;38(4):399-411. doi:10.1016/j.det.2020.05.001

Patel B, Butterfield R. Common skin and bleeding disorders that can potentially masquerade as child abuse. American Journal of Medical Genetics Part C: Seminars in Medical Genetics. 2015;169(4):328-336. doi:10.1002/ajmg.c.31462

Shah SN, Fong H fai, Haney SB, Harper NS, Pierce MC, Neuman MI. Has This Child Experienced Physical Abuse?: The Rational Clinical Examination Systematic Review. JAMA. 2025;334(2):160. doi:10.1001/jama.2025.2216

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa

Date
January 26, 2026