What Causes Lethargy?

Patient Presentation
A 3 year-old male came to clinic with a 2-day history of cough and runny nose. He had a fever to 38.4°C and complained of a sore throat that worsened with the cough, but denied any other pain. “He’s totally lethargic and is just lying around,” according to his mother. She stated that he was sleeping poorly because of the cough. He was drinking and urinating. He was in daycare. The past medical history was non-contributory.

The pertinent physical exam showed a tired appearing male with temperature of 37.8°C, heart rate of 98, and respiratory rate of 22. HEENT showed copious rhinorrhea, mild erythema of the posterior pharynx without exudate and shotty anterior cervical nodes. His lungs had coarse breath sounds and transmitted upper airway sounds, but he was in no respiratory distress. Neurological examination was normal and the patient was quieter but carried on an appropriate conversation.

The diagnosis of a viral upper airway infection was made. The mother was counseled about symptomatic treatment and reasons to call or return to clinic such as signs of respiratory distress. The patient was tested for novel coronavirus (COVID-19) and eventually was negative also.

Discussion
Lethargy is a common word used to describe a person who is drowsy, sluggish, listless and apathetic. Concentration may be difficult and they may have problems doing simple tasks. Many people actual mean fatigue or lassitude or being more tired when they use the word. In medical terms, lethargy is usually used to describe patients who have some type of excessive tiredness and usually have mental status changes with decreased alertness or arousal. Patients and health care providers both usually qualify the term and give more description to better communicate what is implied when using the term. This is true of many words such as “irritable” or “diarrhea” which again are used frequently but may be less precise as to their meaning, or that have different meaning for laypersons or health care professionals. In medicine, true excessive tiredness can be caused by many problems. History is very important. Is this an acute change with a profound decrease in alertness (e.g. sepsis, meningitis, drug toxicity, etc.), or is this more chronic and the patient and family have noticed a slower onset that is just now causing changes to their activities of daily living but not their mental alertness (e.g. anemia, hypothyroidism, etc.).

Learning Point
The differential diagnosis of fatigue (a review can be found here) and lethargy are large with much overlap. Every organ system can be a potential cause, as the body obviously wishes to conserve energy and rest more when it is ill. Also any extreme state can often cause derangement or distress that manifests in some type of mental status change. One must consider what is meant by the term and especially the onset.

The differential diagnosis for lethargy includes:

  • Acute disease presentations
  • Altered homeostatic states
    • Fever – very common cause
    • Dehydration
    • Malnutrition
    • Insufficient sleep
    • Temperature regulation – too hot or cold
  • Chronic disease of major organ systems and/or organ failure
    • Central nervous system
      • Myasthenia gravis
      • Post-ictal state
      • Unrecognized seizures
    • Cardiac
      • Arrhythmias
      • Congenital heart disease
      • Endocarditis
      • Myocarditis
    • Endocrine
      • Addison’s disease
      • Cushing’s disease
      • Hypothyroidism
      • Hyperthyroidism
    • Gastrointestinal
      • Hepatitis
      • Pancreatitis
    • Hematologic
      • Anemia
    • Pulmonary
      • Respiratory failure
      • Severe asthma
    • Renal
      • Pyelonephritis/Urinary tract infection
      • Renal disease
  • Drug – side effects, abuse
  • Electrolyte abnormalities
    • Hypoglycemia
    • Hyperglycemia
    • Hyperammonemia
    • Metabolic abnormalities
  • Infections – acute and chronic
  • Mental health
    • Anxiety
    • Depression
    • Substance use/abuse
  • Trauma
    • Abuse and neglect
    • Traumatic brain injury

Questions for Further Discussion
1. What other terms are commonly used imprecisely by laypersons and healthcare providers?
2. What causes fever? A review can be found here

Related Cases

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: Fatigue and Traumatic Brain Injury.

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.

Illingworth RS. Common Symptoms of Disease in Children. Blackwell Scientific Publications. Oxford, England. 9th Edit. 1988.

Sheldon SH, Levy HB. Pediatric Differential Diagnosis. Raven Press. New York. 2nd Edit. 1985.

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

What Are Potential Problems of Congenital Lung Malformations?

Patient Presentation
A 2-week-old female came to clinic for her health maintenance examination. She was a term infant who had been diagnosed with a congenital pulmonary airway malformation on pre-natal ultrasound in the right chest. The lesion had decreased in size on the last ultrasound before delivery. She was delivered vaginally and had had no problems at delivery, in the hospital or since going home. The pediatric surgeon had seen the patient and wanted to followup in 3 months if the patient remained asymptomatic. Her parents continued to monitor her closely and described “funny breathing” where she will breath slightly more rapidly and then have a short period of not breathing. They do not report labored breathing, and she never has problems with color changes, difficulty feeding or abnormal sounds while breathing.

The pertinent physical exam revealed a 3.980 kg infant with weight gain of 22 grams/day since her last visit. HEENT was normal as was her lung exam. During the examination the parents pointed out the “funny breathing” which was normal periodic breathing.

The diagnosis of an asymptomatic newborn with a prenatally diagnosed congenital pulmonary airway malformation was made. The pediatrician reassured the family about the periodic breathing and reviewed symptoms of respiratory distress and encouraged them to call if she had any problems also with feeding. The patient’s clinical course at her 1-month and 2-month visit showed that she was growing well and continued to be asymptomatic.

Case Image
Figure 128 – AP view of the chest taken on the first day of life shows hazy increased density in the inferior and lateral aspect of the right lung, most probably due to the presence of multiple small cysts in the right lower lobe. The findings were felt to be compatible with a congenital pulmonary airway malformation.

Discussion
Congenital lung malformations (CLM) are commonly identified with prenatal ultrasound and occur in ~1:2400 live births. The natural history shows that lesions may remain the same, enlarge or appear to disappear. There is a wide-range of clinical manifestations. Patients may be asymptomatic or symptomatic at birth and often develop symptoms later.

The overall natural history is difficult to ascertain as there are fewer studies done in older children and adults. Those that are done often lack a good denominator by which to judge the incidence or prevalence. Resection is carried out usually if a patient is symptomatic, but in patients who are asymptomatic the decision can be more difficult. Timing of resection for asymptomatic patients is debated and usually occurs between 6 month – 2 years and try to spare as much tissue as necessary. Main reasons for early treatment of CLMs is the potential for continued or compensatory lung development and growth. Alveolar units continue to develop until age 2 and there can be increased size of existing alveoli before and after this age. Within the alveoli there are changes that can occur up to age 4-5 years. Other studies show many children becoming asymptomatic but again there are complicating issues with these studies.

Common types of CLMs include:

  • Bronchogenic cysts
    • Lesions arise from the bronchial tree usually around the mediastinum, lined with respiratory epithelium that are mucus-filled, may have a component of cartilage
    • Lesions are single or multicystic
    • Usually resected
  • Bronchopulmonary sequestration (BPS)
    • Lesion is pulmonary tissue that does not connect to the tracheobronchial tree and whose arterial blood supply is systemic (not pulmonary)
    • Can be located extra-lobar or intra-lobar
    • Can also be a hybrid lesion with CPAM (see below)
    • Usually resected
  • Congenital pulmonary airway malformation (CPAM) – 1 in 10,000 live births
    • Lesions are multicystic, of various sizes and locations
    • They can be unilobar, bilobar, multifocal and even bilateral
    • Can also be a hybrid lesion with BPS
    • Usually resected
  • Congenital lobar emphysema (CLE)
    • Pulmonary lobe(s) are overdistended as it is thought that there is a localized catilaginous deficiency which causes local bronchomalacia and overdistention
    • Airway collapse with expiration can cause air trapping distally leading to overdistention
    • Often resected but depending on the lesion they may be followed conservatively

Learning Point
CLM outcome is correlated primarily to lesion size. Patients may have outcomes from intra-natal fetal death to being asymptomatic for long periods of time.

Potential problems and complications of CLMs include:

  • Fetal demise
  • *Respiratory problems – tachypnea, oxygen requirement, respiratory collapse
  • *Lesion expansion – mass effect and/or loss of pulmonary tissue
  • *Infection – pneumonia, cyst infection
  • *Malignancy – confused with a primary malignancy (i.e. pleuropulmonary blastoma (extremely rare and seen almost exclusively in young children, bronchioalveolar carcinomas) or potential transformation to a malignancy
  • Cardiac issues – due to mass effect or in BPS high output cardiac failure can occur if a large arterial blood vessel serves it
  • Hemorrhage
  • Spontaneous pneumothorax
  • Resection problems – chest wall deformities, scoliosis, nerve damage, scarring problems

* issues commonly cited as reasons for resection

Questions for Further Discussion
1. What is in the differential diagnosis of respiratory distress? A review can be found here
2. What causes respiratory failure? A review can be found here
3. What are indications for pediatric surgery referral?

Related Cases

    Disease: Congenital Pulmonary Airway Malformation | Birth Defects

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: Birth Defects and Topics.

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.

Boucherat O, Jeannotte L, Hadchouel A, Delacourt C, Benachi A. Pathomechanisms of Congenital Cystic Lung Diseases: Focus on Congenital Cystic Adenomatoid Malformation and Pleuropulmonary Blastoma. Paediatric Respiratory Reviews. 2016;19:62-68. doi:10.1016/j.prrv.2015.11.011

Hall NJ, Stanton MP. Long-term outcomes of congenital lung malformations – Semin Pediatr Surg. 2017 Oct;26(5):311-316. Accessed October 6, 2020. https://pubmed.ncbi.nlm.nih.gov/29110827/

Leblanc C, Baron M, Desselas E, et al. Congenital pulmonary airway malformations: state-of-the-art review for pediatrician’s use. European Journal of Pediatrics. 2017;176(12):1559-1571. doi:10.1007/s00431-017-3032-7

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

How Long Do You Monitor Neonates for Neonatal Abstinence Syndrome (NAS)?

Patient Presentation
A term gestation, newborn female was delivered vaginally to a G2P2 female with a history of heroin addiction. She had been on methadone treatment for 11 months and was doing well in treatment. She had prenatal care and her screening tests were negative. The intrapartum history was non-contributory and at delivery her Apgar scores were 8 and 9. The family history showed poly-drug addiction in the distant past, with only heroin addiction recently. The mother was getting regular mental health treatment. The parents were not married but both were employed and had 2 children by previous relationships in the household. The father had alcohol and tobacco use and no history of other substance use or abuse.

The pertinent physical exam at 30 minutes of life revealed a normal appearing female. Her weight was 3180 grams (25%), length 53 cm (50%) and head circumference of 34.0 cm (50%). She had some molding of her head. Normal red reflexes bilaterally. Heart was regular rate and rhythm without murmur. Lungs were clear for age. She had a 3-vessel cord. Neurologically she had good tone and strength.

The diagnosis of a healthy female was made. The parents agreed to all routine neonatal care at birth and she was monitored using the Finnagan scoring system. The mother was already aware that a cord drug screen would be sent because of the drug use which eventually was negative for any drugs that were not expected. The family also met with the social worker who did not identify any additional specific needs. The patient’s clinical course over the next 7 days did show intermittent elevated Finnagan scores but none were elevated serially so that pharmacological treatment was not needed. The patient was discharged and followed by the local family physician.

Discussion
Neonatal abstinence syndrome (NAS) occurs in the first few days of life and is a complex withdrawal syndrome. The newborn is abruptly cut-off from their exposure to licit or illicit drugs that the mother is chronically consuming and which were being transmitted through the placenta to the fetus. “NAS is a highly variable and severe condition; it may be associated with central and autonomic nervous system dysfunction … and gastrointestinal disorders.” It can cause significant morbidity but is rarely fatal.

Fetal exposure has been increasing in the United States. In 2011-12, almost 5.9% of pregnant women were identified as drug abusers with the highest proportion being in the adolescent age group (15-17 years, 18.3%). A variety of drugs can cause it including opioids, methamphetamines and psychotropic agents. Fetuses exposed to opioids can have prematurity, intrauterine growth restriction, low birth weight, congenital anomalies and NAS. Transplacental passage of opioids increases with increasing gestational age and can also pass into the breast milk. Maternal treatment for drug addition can include long-acting opioids and other medications such as methadone or buprenorphine. Neonates of mothers using buprenorphine usually have milder post-natal courses than those treated with methadone, which is thought to be due to combinations of environment, physiologic and genetic factors.

NAS has variable onset, presentation and severity. Early onset (within 48 hours) is common for heroin, morphine or anti-depressant exposure. Late onset (after 48 hours) is common for methadone or buprenorphine exposure.
Common symptoms include:

  • Central nervous system excitement – irritability, inconsolable crying, jittery, tremors, hypertonicity, seizures
  • Central nervous system depression – lethargy, poor suck
  • Autonomic nervous system – diaphoresis, temperature instability particularly hyperthermia, mottling, frequent sneezing and yawning, poor sleep
    Hyperphagia is common with poor weight gain because the infants have high caloric needs (up to 150-250 kcals/kg/day).

  • Cardiac – tachycardia, hypertension
  • Gastrointestinal – diarrhea, emesis, electrolyte abnormalities, dehydration

Treatment includes keeping the infant with the family as appropriate, in a quiet, low-light environment with gentle handling. Non-nutritive sucking and breastfeeding (if not contraindicated) can also help the infant. Small, frequent amounts of liquid nutrition often help the infant. The Finnegen scoring system is one system designed to be used for monitoring term infants. Patients are serially monitored and scored and can assist in determining if additional interventions are needed including more frequent monitoring, pharmacological initiation, duration and weaning. Pharmacological treatment extends the usual hospital stay significantly with a mean stay of around 3+ weeks.

Learning Point
According to the American Academy of Pediatrics, “An infant born to a mother on a low-dose prescription opiate with a short half-life (eg, hydrocodone; average half-life, 4 hours) may be safety discharged if there are no signs of withdrawal by 3 days of age, whereas an infant born to a mother on an opiate with a prolonged half-life (eg, methadone) should be observed for a minimum of 5-7 days.

Questions for Further Discussion
1. Under what conditions would breastfeeding be encouraged and discouraged in mothers using licit or illicit substances?
2. What is the protocol for pharmacological intervention in NAS at your institution?
3. In your local environment, what is the role of the Department of Human Services, Social work and similar services in the care of a family with a substance exposed infant?
4. What are the potential long-term problems of in-utero exposure to illicit substances?

Related Cases

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: Pregnancy and Opioids and Pregnancy and Drug Use and Opioid Misuse and Addiction.

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.

Hudak ML, Tan RC, Drugs TCO, Newborn TC on FA. Neonatal Drug Withdrawal. Pediatrics. 2012;129(2):e540-e560. doi:10.1542/peds.2011-3212

Raffaeli G, Cavallaro G, Allegaert K, et al. Neonatal Abstinence Syndrome: Update on Diagnostic and Therapeutic Strategies. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 2017;37(7):814-823. doi:10.1002/phar.1954

Tran TH, Griffin BL, Stone RH, Vest KM, Todd TJ. Methadone, Buprenorphine, and Naltrexone for the Treatment of Opioid Use Disorder in Pregnant Women. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 2017;37(7):824-839. doi:10.1002/phar.1958

Isemann BT, Stoeckle EC, Taleghani AA, Mueller EW. Early Prediction Tool to Identify the Need for Pharmacotherapy in Infants at Risk of Neonatal Abstinence Syndrome – Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 2017;37(7):840-848. Accessed September 28, 2020. https://accpjournals-onlinelibrary-wiley-com.proxy.lib.uiowa.edu/doi/10.1002/phar.1948

Holmes AP, Schmidlin HN, Kurzum EN. Breastfeeding Considerations for Mothers of Infants with Neonatal Abstinence Syndrome. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 2017;37(7):861-869. PubMed. Accessed October 6, 2020. tps://pubmed.ncbi.nlm.nih.gov/28488805/

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

How Good is Photoscreening For Young Children’s Vision Problems?

Patient Presentation
A 3-year-old male came to clinic for his health supervision visit. He was well and his mother had no concerns. The past medical history was non-contributory.
The family history was positive for stroke, heart attack, hypertension and glaucoma.

The pertinent physical exam had normal vital signs and his growth parameters were 50% for height and 85% for weight. His physical examination was normal including his eye examination. The diagnosis of a healthy male was made. Two days later his photoscreening results from the centralized screening service showed a possible amblyopia. The patient was referred to the ophthalmologist who found he had mild hyperopia and a prescription for spectacles was given. He was to be followed up in 2-3 months.

Discussion
Amblyopia is a decrease in visual acuity because of abnormal vision development in young children. It is sometimes called “lazy eye.” It is the leading cause of unilateral vision loss in children and occurs in 1-6% of children and causes permanent vision loss in 2.9% of adults. “Amblyopia is thought to develop during a critical time in infancy and early childhood when visual development depends on the eyes and the brain’s visual cortex working together. Inadequate stimulation of the visual pathways leads to disuse of the visual cortex and resultant amblyopia.” If the visual inputs are not the same, then the poorer visual signal (e.g. more blur, discordant visual image) will be suppressed by the visual cortex, and the reliance on the superior image will occur. Overtime this can results in visual loss in the poorer eye.

Major causes of amblyopia include:

  • Strabismic amblyopia- eyes are misaligned. The visual image from the deviating eye is suppressed. If not treated it can result in binocular vision and depth perception.
  • Anisometropic amblyopia – visual acuity in the eyes is not symmetric. The blurrier (higher refractive error) image is suppressed. Sometimes this is called refractive amblyopia.
    Farsightedness (hyperopia, image is focused behind the retina), near sightedness (myopia, image is focused in front of the retina) and astigmatism (image is focused unevenly on the retina) are often seen with anisometropic amblyopia.
  • Combined strabismic and anisometropic amblyopia – eyes are misaligned and visual acuity is not symmetric. The chronically blurred imaged is suppressed.
  • Ametropic amblyopia – visual acuity in both eyes has a high refractive error resulting in blurred vision in both eyes. There is inadequate development of the visual cortex in both eyes.
  • Deprivation amblyopia – visual acuity is caused by obstruction such as cataract or ptosis. The obstructed image is suppressed.

Patients with a family history of congenital eye abnormalities including amblyopia, cataracts and glaucoma, or if parents have strabismus, should be referred for ophthlamological care. Treatment for children under age 7 is much better than older children. Treatment includes spectacles, patching (usually of the better eye to improve use of the worse eye), atropine (blurs the vision in the better eye encouraging use of the worse eye) and possibly surgery. Careful monitoring is important as there is a high rate of recurrence.

Learning Point
Families should be asked if they have any concerns about their child’s vision and if so, usually referral should be made. Families may say they see strabismus or a wandering eye, squinting or torticollis. Turning of the head is done to try to improve the visual image. Vision examination can include inspection of the structures, movement of the eyes, alignment, pupils and red reflexes/retinal examination. Visual acuity testing is recommended starting at age 3-5 years. Children who have vision in either eye or both eyes of > 20/30 should be referred.

Photoscreening has the advantage of being relatively quick to perform, needs less cooperation from the patient, can be performed in non-verbal/younger children, and records the images for review. Photoscreening using a dedicated photoscreening device or more recently using a smartphone application, have had good results. The patient is asked to look at a light on the photoscreener and an image is taken. The image can be analyzed using computer software and/or human review and analysis.

A study of a smartphone photoscreening application in children 1-6 years old in pediatric ophthalmology practices found with manual grading and automatic computer grading (given in parentheses) that the sensitivity was 76% (65%), specificity was 85% (83%) with a positive predictive value of 0.76 (0.69) and negative predictive value of 0.85 (0.8). This study showed that not only was smartphone photoscreening feasible, but was quite good at screening for potential vision problems. Smartphone photoscreening has the advantages of being more ubiquitously available and thus children in almost any location can be screened.

A study of photoscreening using a handheld digital photoscreener in primary care offices validated the technology showing an overall referral rate of 10% to an ophthalmologist with suspected astigmatism, anisometropia and strabismus being the most common reasons. The overall positive predictive rate was 0.60. “…[O]ver 60% of children referred were found to have [amblyopia risk factors] and 13% had amblyopia detected on examination, both of which are significantly more than in the general population, which is thought to be 15-20% for [amblyopia risk factors] and 1-2% for amblyopia.”

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Questions for Further Discussion
1. What are causes of blindness in children? A review can be found here
2. What causes ptosis? A review can be found here
3. What causes congenital cataracts? A review can be found here

Related Cases

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: Amblyopia and Vision Impairment and Blindness

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.

Bregman J, Donahue SP. Validation of photoscreening technology in the general pediatrics office: a prospective study. J AAPOS. 2016;20(2):153-158. doi:10.1016/j.jaapos.2016.01.004

Arnold RW, O’Neil JW, Cooper KL, Silbert DI, Donahue SP. Evaluation of a smartphone photoscreening app to detect refractive amblyopia risk factors in children aged 1-6 years. Clin Ophthalmol. 2018;12:1533-1537. doi:10.2147/OPTH.S171935

McConaghy JR, McGuirk R. Amblyopia: Detection and Treatment. Am Fam Physician. 2019;100(12):745-750.

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