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Patient Presentation
A 2.5-year-old male came to clinic for his health supervision visit. He was an only child, had moved many times since he was born, and had had only intermittent healthcare. His mother had no concerns about his health or development and described him as a happy child who would play by himself without causing problems. He liked to play with spinning or wheeled toys for long time periods. He had little contact with children of his own age and the adults were mainly family members who liked him because “he didn’t cause too many problems.” His mother said that he said a few words but didn’t put many together. Her main concern was that he spent a lot of time rocking his body wherever he was. It never bothered him or others, and he would stop if engaged. Once in a while, she said that he would also “twirl” his body around and occasionally would fall on the floor but never hurt himself. The past medical history revealed a term birth but with little prenatal care.

The pertinent physical exam showed a happy boy, who would rock in the chair or on the table if not actively engaged. His vital signs were normal and growth was 25% for all parameters. He would look at the examiner but only fleetingly, and would look and smile at his mother for longer. He would vocalize in the room but had no words. His neurological examination was normal but he also tended, but not always, to hold his elbows flexed with arms slightly extended from the body. His mother said she called him “her little bird,” when he would do this, and with questioning she did not describe any other movements of the arms or hands.

The diagnosis of a child who had neurodevelopmental delay in at least speech and socialization was noted, along with the body rocking sterotypie and arm positioning preference. The pediatrician discussed that the body rocking could be a way to ease boredom or to self-soothe but could also be a sign of a developmental problem, which he was worried about because of the speech delay and limited socialization seen in the office. The mother acknowledged that he did do some unusual things like the body rocking that she was worried about but she felt, “he just needs some more time to grow.” She agreed to receiving his routine health care including some catch-up vaccinations and referral for additional developmental evaluation. The patient’s clinical course reveled that he followed up once for additional vaccines and had started his evaluations including speech. He was lost to followup after that visit.

Discussion
Stereotypies are “…patterned, repetitive, purposeless, involuntary movements that are also rhythmic and continual and tend to change little over time.” They occur at all times of the day, and can get worse with stress or heightened emotions including happiness. Stereotypies more often occur in children with developmental disabilities (up to 61%), sensory impairments (e.g. blindness) or social deprivation. They can be present more often in patients with autism (up to 88%). They can be seen in ~7% of normally developing children too. Their onset is before age 3 years and tend to improve over years, but often persist into adulthood.

Examples of simple stereotypies including thumb sucking, nail biting, leg shaking, and teeth grinding. Complex motor sterotypies’ examples include hand flapping, arm waving, opening/closing of the hands or finger wiggling, orofacial movements and mouth opening.

Primary complex stereotypies occur in patients without an underlying neurodevelopmental condition whereas secondary occurs in those with other such conditions such as Lesch-Nyhan syndrome. Co-morbid diagnoses that can occur with sterotypies include attention deficit hyperactivity disorder, anxiety, obsessive-compulsive disorder, tics, developmental coordination disorder, and learning disorders.

Learning Point
Body rocking is a stereotypie that can be seen in different situations including:

• Self-stimulation, helps with boredom
• Self-soothing, helps with concentration
• Learned
• Situational
• Neurodevelopmental problems including Autism – for some Autism patients this may be a way to be able to pay more attention and process what is going on around them.
• Genetic – Angleman syndrome, Fragile X syndrome, Lesch-Nyhan syndrome, Cornelia de Lange syndrome, Rett syndrome, etc.

Body rocking differential diagnosis also includes seizures, motor tics and other movement disorders such as ataxia, dystonia, myoclonus, tremor, Tourette syndrome, rhythmic movement disorder

The Motor Sterotypy Severity Scale is one of several caregiver rating scales. It looks at the number of stereotypies, their frequency, intensity and how much they impair the patient globally. For example, this patient had only 1 identified sterotypie (body rocking), it very frequently but not always occurred, it was quite marked in intensity but wouldn’t cause injury to the patient, and at that time was causing only subtle to minor problems for the patient and family. Had the child been older or in an out-of-home setting, the behavior may potentially have caused additional problems for the child or family.

Questions for Further Discussion
1. What is the criteria for diagnosing autism spectrum disorder?
2. How does Fragile X syndrome present?
3. What developmental screening is recommended to be performed during health maintenance visits?
4. How often do you see sterotypies in your practice?

Related Cases

Disease: Body Rocking | Child Development | Child Mental Health

Symptom/Presentation: Developmental Delay | Health Maintenance and Disease Prevention

Specialty: Developmental Disabilities | Neurology / Neurosurgery

Age: Toddler

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: Child Mental Health

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.

Katherine M. Stereotypic Movement Disorders. Semin Pediatr Neurol. 2018;25:19-24. doi:10.1016/j.spen.2017.12.004

Zalta A, Hou JC, Thonnat M, Bartolomei F, Morillon B, McGonigal A. Neural correlates of rhythmic rocking in prefrontal seizures. Neurophysiol Clin. 2020;50(5):331-338. doi:10.1016/j.neucli.2020.07.003

McCarty MJ, Brumback AC. Rethinking Stereotypies in Autism. Semin Pediatr Neurol. 2021;38:100897. doi:10.1016/j.spen.2021.100897

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

Patient Presentation
A 9-month-old, previously healthy, male came to clinic for followup 2 days after being discharged from the pediatric intensive care unit (PICU). He had been diagnosed with croup as an outpatient in clinic and started on dexamethasone. That night he worsened and was taken to the emergency room and was admitted to the PICU because of respiratory distress. His physical examination at admission had a respiratory rate of 64 breaths/minutes, heart rate of 110 beats/minute, normal blood pressure and temperature and an oxygen saturation of 86-88% on room air. His weight was decreased by 560 grams from a recent previous weight. His capillary refill was 2-3 seconds and his lips were slightly dry. He had marked tracheal tugging, nasal flaring, intercostal retractions and abdominal breathing. He was not cyanotic. He had coughing and stridor. HEENT had rhinorrhea. Lungs had rales but no rhonchi. The laboratory evaluation had a respiratory swab that was positive for parainfluenza virus, a blood gas with hypoxemia and no hypercapnia, and a chest radiograph with diffuse interstitial markings.

The diagnosis of acute respiratory distress with pulmonary edema due to parainfluenza virus was made. Over the next 2 days the patient’s clinical course showed that he did not require mechanical ventilation but did require continuous positive airway pressure and supplemental oxygen up to 40%. He was slowly weaned off support and was transferred to the floor where he continued to receive intravenous fluids until he was able to maintain his hydration. He was discharged after 4 days.

The pertinent physical exam today showed a wary infant with normal vital signs and oxygen saturation of 94-97%. Weight was back to normal.
He had rhinorrhea and no stridor but did have a hoarse cry. His lungs had no adventitial breath sounds. The patient’s clinical course showed that he had been improving since discharge, and had no obvious respiratory or hydration problems at the time. He was also scheduled to follow-up with pulmonary medicine in 2 weeks.

Discussion
Pulmonary edema is a potentially life threatening condition due to accumulation of excess fluid in the alveolar spaces and walls of the lung.
Patients show increased respiratory effort or distress (e.g. tachypnea, dyspnea or difficulty talking, use of excessory muscles, nasal flaring, tracheal tugging, etc.) and clinicians should beware signs of tiring (e.g. bradypnea and decreased effort) as the patient may be failing. Patients may have rales or rhonchi on pulmonary examination, and pallor or color changes may be noted. Blood gas analysis shows evidence of hypoxemia and often hypercapnia depending on the severity and underlying cause.

As with most diseases and problems, treating the underlying cause is fundamental. In addition, ventilatory management (including potential ventilatory pressure) to maintain adequate gas exchange is key. Providing supplemental oxygen is primary for most situations. Newborns with ductal dependent lesions, and hyperoxia-induced pulmonary vasodilatation would be a two of exceptions. Oxygen should be administered in the least invasive and comfortable manner that supplies the necessary oxygen. Other methods to potentially improve gas exchange can include emptying the stomach or elevating the head of the bed or placing the patient in another position (e.g. prone).

An overview of croup can be found here.

Learning Point
Pulmonary edema is usually divided into two types: cardiogenic pulmonary edema, or non-cardiogenic pulmonary edema. Cardiogenic pulmonary edema is due to increased hypostatic pressure in the pulmonary circulation. Noncardiogenic pulmonary edema is caused by some type of lung injury which causes increased pulmonary vascular permeability with resultant increase in pulmonary vascular permeability and accumulating fluid.

Causes of pulmonary edema include:

• Acute respiratory distress syndrome (ARDS) is a common reason for pulmonary edema and “is a rapidly progressive noncardiogenic pulmonary edema that initially manifests as dyspnea, tachypnea and hypoxemia, and then quickly evolves into respiratory failure.”
  A diagnosis of ARDS in pediatric patients:
  • Occurs within 7 days of insult
  • The respiratory failure is not fully explained by cardiac failure or fluid overload
  • New pulmonary infiltrates consistent with parenchymal disease
  • Specific oxygenation levels need to be required depending on if the patient is mechanically ventilated and if there is other concomitant problems such as chronic lung disease, or heart disease (e.g. cyanotic congenital heart disease or left ventricular dysfunction).
• Cardiac
  • Congenital heart disease
  • Congestive heart disease/ Left ventricular failure
  • Pulmonary venous obstruction
• Infection
  • Pneumonia
  • Croup
  • Epiglottitis
• Pulmonary
  • Airway obstruction
  • Reexpansion after pneumothorax, effusion, atelectesis, tumor, surgery, etc.
    Reexpansion pulmonary edema is not very common but occurs after rapid reexpansion of the lung after a few days of collapse.
• Trauma
  • Burns
  • Chest
  • Inhalation
  • Neurogenic due to increased intracranial pressure. Neurogenic pulmonary edema can be hard to differentiate from cardiogenic pulmonary edema.
    The pathophysiology is not well understood but is thought to begin with increased intracranial pressure leading to increased catecholamines and sympathetic storm, which then leads to systemic vasoconstriction and accumulating blood in the pulmonary system. Increased blood leads to pulmonary hypertension, increased capillary permeability and thereby pulmonary edema.
  • Single or multiple organ system
• Miscellaneous
  • Acute mountain sickness
  • Heroin overdose
  • Transfusion reaction
  • Perinatal lung disease

Questions for Further Discussion
1. What are causes of respiratory failure? A review can be found here
2. What are indications for using dexamethasone? A review can be found here
3. What are normal blood gas values?
4. What is the difference between stridor and stertor? A review can be found here

Related Cases

Disease: Croup | Throat Disorders | Lung Diseases

Symptom/Presentation: Cough | Respiratory Distress | Stridor

Specialty: Critical Care | Allergy / Pulmonary Diseases | Infectious Diseases

Age: Infant

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: Throat Disorders and Lung Diseases.

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.

Kira S. Reexpansion pulmonary edema: review of pediatric cases. Paediatr Anaesth. 2014;24(3):249-256. doi:10.1111/pan.12283

Khemani RG, Smith LS, Zimmerman JJ, Erickson S, Group for the PALICC. Pediatric Acute Respiratory Distress Syndrome: Definition, Incidence, and Epidemiology: Proceedings From the Pediatric Acute Lung Injury Consensus Conference. Pediatr Crit Care Med. 2015;16(5_suppl):S23. doi:10.1097/PCC.0000000000000432

Hirsch AW, Nagler J. Reexpansion Pulmonary Edema in Pediatrics. Pediatr Emerg Care. 2018;34(3):216-220. doi:10.1097/PEC.0000000000001435

Simma L, Neuhaus TJ. Common diagnosis at an unusual age – pulmonary oedema in a toddler. BMJ Case Rep. Published online October 21, 2018:bcr-2018-225389. doi:10.1136/bcr-2018-225389

Saguil A, Fargo MV. Acute Respiratory Distress Syndrome: Diagnosis and Management. Am Fam Physician. 2020;101(12):730-738.

Lo-Cao E, Hall S, Parsell R, Dandie G, Fahlström A. Neurogenic pulmonary edema. Am J Emerg Med. 2021;45:678.e3-678.e5. doi:10.1016/j.ajem.2020.11.052

Saguil A, Fargo MV. Acute Respiratory Distress Syndrome: Diagnosis and Management. Am Fam Physician. 2020;101(12):730-738.

Malek R, Soufi S. Pulmonary Edema. In: StatPearls. StatPearls Publishing; 2022. Accessed February 6, 2023. http://www.ncbi.nlm.nih.gov/books/NBK557611/

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

Patient Presentation
An 8-year-old male came to the emergency room for daily fever for 10 days. The patient had a cough, runny nose and a fever of 101F at least daily. The fever occurred mainly in the evening but sometimes during the night. Maximum temperature was 102.4F 5 days ago. The last recorded temperature was the evening before at 100.1F. The fever was responsive to antipyretics, and he was taking some dextromethorphan as well.

The past medical history revealed that he was being treated by a psychiatrist for depression that he was taking a selective serotonin reuptake inhibitor for, and attention deficit disorder which 3 weeks previously his long-acting methylphenidate had been increased. The family said that it seemed to be working and denied any problems such as tics, sleep or eating problems. He had no fever during the week after the medication changed.

The pertinent physical exam showed obvious rhinorrhea but his mucous membranes were moist. Vital signs were normal including a temperature of 98.6F. His weight was tracking at the 25%. HEENT showed rhinorrhea and his lungs were clear. The rest of his examination was normal.

The laboratory evaluation was positive for influenza and negative for COVID. The diagnosis of influenza was made. He was discharged from the ER with symptomatic care, but while discussing his care, the attending physician reminded the resident that one should try to look at the medications and see if they would be a problem. “This is an infectious history and is caused by influenza but remember that SSRIs and ADHD medication can cause serotonin syndrome. The timing is wrong here because serotonin syndrome occurs in the first day or so, not a week later and causes a lot of other autonomic nervous system problems and nervous system excitability. You are going to see a lot of patients taking these medications and usually they don’t cause problems, but they are so common that it’s bound to show up in your emergency room someday,” he remarked.

Discussion
Serotonin syndrome (SS) is a clinical diagnosis and problem which can be seen in patients of all ages. Classically SS presents with changing mental status, autonomic dysfunction and neuromuscular excitability. It is caused by increased serotonin levels because of therapeutically increasing the dose of a medication already being taken, adding an additional serotoninergic medication or one that potentiates serotonin, overlapping transition when changing medications, or intentional or unintentional overdose. It has become more common especially as selective serotonin reuptake inhibitors (SSRIs) have been used more along with other mental and behavior health medication. Risk of SS is more common in middle aged and older people, but anyone starting or changing medications could have it occur.

Drugs associated with SS include:

• Increase the amount of serotonin precursor or agonists – fentanyl, lithium, tryptophan, LSD
• Increase serotonin release – amphetamines, anorectics, cocaine, Ecstasy
• Decrease serotonin breakdown – monoamine oxidase inhibitors (MAOIs), antibiotics of linezolid, tedizolid, and others such as methylene blue
• Decrease serotonin reuptake – SSRIs, opioids, antiemetics and antiepileptics
• Inhibitors of CYP2D6 and CYP3A4 – anti-infectives – ciprofloxacin, erythromycin fluconazole, ritonavir

Diagnosis is clinical but two different criteria can help with the diagnosis.

Hunter criteria – “The patient must have taken a serotonergic agent and have one of the following:
Spontaneous clonus
Inducible clonus plus agitation or diaphoresis
Ocular clonus plus agitation or diaphoresis
Inducible clonus or ocular clonus, plus hypertonia and hyperthermia
Tremor plus hyperreflexia”

Sternback criteria – “The patient must be using a serotonergic agent, must have no other causes of symptoms, must not have recently used a neuroleptic agent, and must have three of the following:

Mental status changes
Agitation
Hyperreflexia
Myoclonus
Diaphoresis
Shivering
Tremor
Diarrhea
Incoordination
Fever”

The differential diagnosis includes neuroleptic malignant syndrome which is due to dopamine antagonists or withdrawal from one. It occurs days to weeks after, not usually within 24 hours. Resolution is also longer (9 or so days). Anticholinergic toxicity occurs with taking an anticholinergic agent usually within 1-2 hours with resolution within hours to days. Malignant hyperthermia is associated with inhaled anesthetics and some muscle relaxants and occurs usually very suddenly within minutes to hours.

Preventing SS starts with appropriate prescribing of the medication using minimum effective dosing and education to ensure that the patient is taking the medication properly. Patients may need multiple drugs to treat their main mental health or other problem which can increase the risk. Risk of SS is increased with an increased dosing change or addition of another medication. Transitioning between medications can require different wash-out time periods so working with a pharmacist can help to balance the risk of SS and the need for continued treatment for the underlying mental health or medical problem.

Learning Point
There is a range of symptoms from mild to severe and life-threatening. Overall, 40% of patients will have mental status changes and autonomic changes and 50% will have neuromuscular excitability. Symptoms do not need to occur simultaneously. Symptoms occur within 24 hours of changes to a serotonergic agent and resolution can also be within 24 hours. Treatment is mainly to stop the drug and support the patient. Anti-serotonergic agents may also be used.

• Mild
  • Mental status – anxiety, insomnia, restlessness
  • Autonomic dysfunction – diaphoresis, mydriasis, tachycardia
  • Neuromuscular excitability – hyperreflexia, myoclonus, tremor
  • Treatment – stopping the drug, admission to monitor clinical status, supportive therapy and symptom management such as intravenous hydration and possibly benzodiazepine
• Moderate
  • Mental status – agitation
  • Autonomic dysfunction – flushing, increased blood pressure, hyperthermia (<104F or 40C), gastrointestinal problems with nausea, emesis, diarrhea, hyperactive bowel sounds
  • Neuromuscular excitability – induced or spontaneous clonus, opsoclonus
  • Treatment – stopping the drug, admission to monitor clinical status, supportive therapy and symptom management such as intravenous hydration and possibly benzodiazepine, emesis control with a non-serotonergic agent, cooling for fever
• Severe – this can cause potentially multisystem organ failure within hours
  • Mental status – coma, confusion, delirium
  • Autonomic dysfunction – hyperthermia (> 104F or 40C), changing blood pressure
  • Neuromuscular excitability – respiratory failure, rigidity, seizures (tonic-clonic)
  • Treatment – stopping the drug, admission to intensive care as patient will likely need mechanical ventilation, and hyperthermia needs cooling treatment.

Questions for Further Discussion
1. What are some common toxidromes?
2. What are common treatments for anxiety and depression?
3. What are services that a poison center can offer?

Related Cases

Disease: Influenza | Serotonin Syndrome | Antidepressants

Symptom/Presentation: Cough | Fever and Fever of Unknown Origin |
Rhinitis

Specialty: Emergency Medicine | Infectious Diseases | Pharmacology / Toxicology | Psychiatry and Psychology

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 this topic: Antidepressants

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.

Wang RZ, Vashistha V, Kaur S, Houchens NW. Serotonin syndrome: Preventing, recognizing, and treating it. Cleve Clin J Med. 2016;83(11):810-817. doi:10.3949/ccjm.83a.15129

Mendelsohn J, Coffey BJ. Serotonin Syndrome in an Adolescent Girl. J Child Adolesc Psychopharmacol. 2019;29(10):783-786. doi:10.1089/cap.2019.29175.bjc

Hutchison L, Clark M, Shaffer S. Insidious Onset of Serotonin Syndrome in a 6-Year-Old Boy. J Am Acad Child Adolesc Psychiatry. 2021;60(2):201-202. doi:10.1016/j.jaac.2020.08.439

French S, Wray C. Serotonin Syndrome and Hippocampal Infarction. Pediatr Neurol. 2019;90:66-67. doi:10.1016/j.pediatrneurol.2018.10.004

Scotton WJ, Hill LJ, Williams AC, Barnes NM. Serotonin Syndrome: Pathophysiology, Clinical Features, Management, and Potential Future Directions. Int J Tryptophan Res IJTR. 2019;12:1178646919873925. doi:10.1177/1178646919873925

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