How Commonly Are Brain Tumors Seen in Spasmus Nutans?

Patient Presentation
A 4-month-old male came to clinic for his well child check. His parents reported that he was doing well. He was breastfeeding vigorously and was smiling and trying to roll over. The past medical history was non-contributory. The family history was negative for any neurological, ophthalmological or genetic problems.

The pertinent physical exam showed a smiley baby with growth parameters in the 10-50% and trending appropriately. Eye examination revealed pupils that were equal, round and reactive to light, normal red reflexes bilaterally. However, there was bilateral, intermittent, lateral, nystagmus that varied in amplitude. During the examination the nystagmus wouldn’t always occur. His head showed some very mild positional plagiocephaly on the right occiput without changes to the ear or face. There was a mild right sternocleidomastoid muscle torticollis as well. The neurological examination was normal. The diagnosis of nystagmus was made. With further questioning the parents said that a family member had noted it the previous week, but that they really didn’t think much of it as he overall seemed well. They denied any other unusual movements or posturing and no seizures. “His head is always turned toward the left and he always lays on that side,” his mother offered. The pediatrician discussed the findings and instructed the family how to improve the positioning for his plagiocephaly as well as starting to do some stretching exercises of his neck. An ophthalmologist examined the infant within the week and found bilateral, horizontal and vertical nystagmus that was intermittent and of low amplitude. Electroretinography was negative. He also noted head bobbing in the infant and the torticollis, and

the diagnosis of spasmus nutans was made. He ordered a head magnetic resonance imaging study that was negative. Over the next few weeks, the torticollis improved but needed more intensive physical therapy without cranial banding. At his 9 month examination, the patient still had intermittent nystagmus and head bobbing.

Discussion
Nystagmus is periodic eye movement that is involuntary where there is a slow drift of fixation. The slow drift can be followed by a fast saccade back to fixation. The pathological movement is the slow phase, but nystagmus is described by the fast phase (i.e. horizontal nystagmus, vertical nystagmus).

Spasmus nutans (SN) is a movement disorder that is rare. The classic triad includes nystagmus, head bobbing or titubation, and torticollis, with these problems being in the absence of any ophthalmological or neurological condition. Onset is in the first year of life but ranges from 6-36 months. Time to resolution is sometimes stated as 1-2 years, but others disagree citing longer time frames. There is no harm to visual acuity.

  • The SN nystagmus is usually intermittent, high frequency of small or low amplitude. It is “…variably disconjugate or disjunctive, greater in the abducting eye, and may have a vertical component.” Amblyopia and strabismus may coexist with SN.
  • The head bobbing is irregular may have both vertical and horizontal components.
  • Torticollis occurs as the child moves the head to try to obtain better visual acuity. The differential diagnosis of torticollis can be reviewed here.

The differential diagnosis of SN includes ophthalmic problems such as congenital (infantile) nystagmus (a review can be found here), refractive disorders and retinal diseases, and problems of the central nervous system such as optic chiasm gliomas, diencephalic tumors, brain malformations, opsoclonus-myoclous, and bobble-head doll syndrome.

Learning Point
As SN is rare, reports of complications are even rarer but most concerning are potential underlying brain tumors particularly optic chiasm gliomas or neurological abnormalities. Rates of optic gliomas have been reported in small studies from 0% to 9%.

In a 2017 study of 40 patients with SN who had magnetic resonance imaging, 25 patients had normal findings, none had optic nerve gliomas or other masses, and 2 had optic nerve hypoplasia. Other patients, including many who were otherwise healthy, had a variety of imaging findings which could or could not be clinically significant. The authors concluded that “…the risk of optic gliomas in children without other neurological deficits or signs concerning for intracranial mass lesions is very low.”

In a 2018 long-term followup study of 22 patients, 17 had neuroimaging and all 17 were negative for any space occupying lesions, and 1 “…had findings suggesting hydrocephalus….”

In this same 2018 long-term followup study, their patients had an average age of SN onset of 9.7 months (range 3-33 months ) and followup of 62.6 months (range 7-156). Nystagmus “…resolved in 4 [patients], from 2 to 49 months after presentation (mean 20 months), at ages ranging from 11-54 months (mean 30 months).” Head bobbing “…resolved during follow-up ranging from 1 to 49 months (mean 20 months), at ages ranging form 10 to 54 months (mean 27 months).” Torticollis improved in only 1 of 7 children, 39 months after presentation at the age of 51 months. During the study, no patients developed additional problems such as myopia, photophobia, night blindness or specific retinal pathology. With this data, the authors state that they advise families “…that many children do well, assuming normal imaging, but that nystagmus, torticollis and even titubations may persist.”

Questions for Further Discussion
1. What causes strabismus?
2. What are common movement disorders in children? 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 this topic: Eye Movement Problems

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.

Delorme C, Gras D, Roze E. Spasmus Nutans: More Than Meets the Eye. Pediatr Neurol. 2015 Oct;53(4):367-8.

Bowen M, Peragallo JH, Kralik SF, Poretti A, Huisman TAGM, Soares BP. Magnetic resonance imaging findings in children with spasmus nutans. J AAPOS. 2017 Apr;21(2):127-130.

Parikh RN, Simon JW, Zobal-Ratner JL, Barry GP. Long-Term Follow-up of Spasmus Nutans. J Binocul Vis Ocul Motil. 2018 Oct-Dec;68(4):137-139.

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

What Are Treatment Options for Pediatric Onycomycosis?

Patient Presentation
A 15-year-old male came to clinic because of his left great toenail had become yellowish and thicker over the last 1-2 months. He played multiple sports and had tinea pedis during basketball season 3-4 months earlier, but had noticed this during the spring baseball season. He denied any erythema, burning, itching or pain in his feet or nails. He had no changes to his hands. “I’ve been changing my socks more often, using shower shoes in the locker room and airing out my feet at home, but now I have this,” he commented. The past medical history was non-contributory. The family history was negative for dermatological problems with the exception of atopic dermatitis in one sister.

The pertinent physical exam showed a healthy male with normal vital signs and weight in the 50% and height in the 90%. His dermatological examination was negative including his hands with the exception of his left great toe with showed hyperkeratotic, easily friable nail with yellowish coloration. There was no erythema, drainage, pain or other problems with the nail, along with no signs of other affected nail or tinea pedis. The diagnosis of onychomycosis was made. A culture was sent which eventually grew Trichophyton rubrum. He was treated with intraconazole daily for 12 weeks. He appeared to have clinical resolution at this time. His nailbed returned to normal by 9 months.

Discussion
Onycomycosis is a fungal infection of the nails. It has a world-wide prevalence of 0.3% with some geographical variations such as in the U.S. it is 0.44%. It is an uncommon problem especially in children. It is very uncommon in those under 6 years and only very sporadic case reports in those under 2 years. The lower incidence is felt to be due to children’s faster nail growth, smaller surface to infect, reduced exposure to fungi, lower prevalence of tinea pedis and especially less cumulative trauma. Onycomycosis is more common in families (unsure if this is due to genetic factors or family members having more onycomycosis and therefore increased environmental exposure), people with immunodeficiencies (especially adult diabetic patients or HIV), and people with Down’s syndrome. Trauma is a major predisposing factor as is hyperhidrosis.

Clinical presentation includes color changes of the nail plate (often yellowish), debris under the nail bed, hyperkeratosis and thickening of the nail, and onycholysis.

Family members should also be checked for onycomycosis and tinea pedis.

Distal and lateral subungual onycomycosis is the most common. Dermatophytes especially are the usual cause especially Trichophyton rubrum but other causes include Candida sp. and nondermatophyte species such as Aspergillus.

Learning Point
Onycomycosis is difficult to treat and can recur. Systemic medications (often prolonged) are often the mainstay, but topical medications are also being used more. Because onycomycosis is uncommon in the pediatric age groups, clinical treatment studies very limited.

A 2017 review article found 7 studies with the sample size from 1-40 patients (5 studies had only 8 or fewer patients enrolled). In the largest study of 40 patients, a control or ciclopirox nail lacquer was applied daily for 32 weeks. At 32 weeks, 34.2% were cured. At one year, 12 patients were available to be evaluated and 11 of the 12 were cured. During the study, 2 patients using the vehicle also had cure, which the authors believe may be due to “…weekly removal of lacquer and mechanical trimming….”

A 2018 review of treatment agents in children found “…antifungal therapies used to treat onychomycosis in children are associated with a low incidence of adverse events. Current dosing regimens for antifungal drugs are effective and appear safe to use in children….” The weighted average cure rates were highest for intraconazole (oral), terbinafine (oral) and ciclopirox (topical). Cure rates depend on definition (i.e. clinical cure and/or myocological cure.

Other topical treatments include amorolfine, bifonazole, terbinafine, ketoconazole, efinazonazole and tavaborole. Systemic medications frequently include intraconazole, terbinafine, griseofulvin and fluconazole.

Questions for Further Discussion
1. What are some potential side effects of systemic oral treatment for onychomycosis?
2. What causes white nails (leukonychia)? For a review, click here.
3. What does tinea pedis look like?

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: Nail Disease and Fungal Infections.

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.

Chadeganipour M, Mohammadi R. Causative Agents of Onychomycosis: A 7-Year Study. J Clin Lab Anal. 2016 Nov;30(6):1013-1020.

Solis-Arias MP, García-Romero MT. Onychomycosis in children. A review. Int J Dermatol. 2017 Feb;56(2):123-130.

Eichenfield LF, Friedlander SF. Pediatric Onychomycosis: The Emerging Role of Topical Therapy. J Drugs Dermatol. 2017 Feb 1;16(2):105-109.

Gupta AK, Mays RR, Versteeg SG, Shear NH, Friedlander SF. Onychomycosis in children: Safety and efficacy of antifungal agents. Pediatr Dermatol. 2018 Sep;35(5):552-559.

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

What Does the Liver Do?

Patient Presentation
A teenage boy was talking at dinner one night explaining that a student in his high school had had a motor vehicle accident and was in the hospital. “He’s doing okay but they said he cut his liver. I don’t know what that really means or what your liver really does?” he asked. His pediatrician mother explained that the student might have a liver laceration. “You can still live without part of your liver, but it’s pretty important,” she explained. “It does all kinds of things…,” and she started to list them. His eyes got wider and he finally stopped her. “Okay so I get it. It’s pretty important so I should take care of it right? This is part of the don’t drink alcohol and don’t do drugs talk isn’t it?” he asked. She smiled and said, “You asked the question. I answered it. And yes drugs and alcohol aren’t good for your liver because it is the major detoxifier for your body. They’re not good for any other part of your body too,” she reiterated. “Plus, make sure you always wear your seatbelt. He may have hurt his liver, but he probably saved his life with the seatbelt,” she also added.

Discussion
The liver is one of the largest organs in the body, weighing just over 3 pounds in an adult. It is found in the upper right abdomen, under the right dome of the diaphragm. Grossly, it has asymmetric lobes with the right being larger than the left. The lobes are separated by a fibrous connective tissue band that also anchors the liver in the abdominal cavity. The gallbladder is located on the inferior surface of the liver and stores bile, which is then released into the duodenum. Microscopically, the liver cells are arranged in lobules with canals carrying blood vessels and bile ducts. At any moment about 10-13% of the body’s blood volume is in the liver. Blood with its nutrients, medications and toxic substances comes to the liver from the portal vein. The liver processes the substances and the resulting end products are released back into the blood and eliminated by the renal system, or released into the bile and eliminated by the gastrointestinal system.

Patients with liver problems can present in many different ways including hepatomegaly, jaundice (see below) and abnormal laboratory testing. In children inborn errors of metabolism must be considered.

Some common liver diseases are below.

Learning Point
Liver functions include:

  • Metabolism
    • Bile acid production – eliminates toxins, helps to break down and absorb fat in the small intestine, about 800 – 1000 ml/day of bile is made
    • Protein production
      • Amino acids
      • Coagulants and clotting factor regulation
      • Fat binding proteins
      • Immune factors
      • Plasma proteins – e.g. albumin, lipoproteins, transferrin, carrier proteins
    • Cholesterol production
    • Energy metabolism – e.g. glycolysis, gluconeongensis, lipogenesis, ketogenesis, amino acid production
  • Storage
    • Glycogen storage and glucose homeostasis
    • Mineral storage – iron and copper
  • Toxin breakdown and excretion
    • Alcohol
    • Ammonia
    • Bilirubin
    • Drug clearance
      • Drugs are either activated (often with the P450 catalyzing enzymes) or detoxified (e.g. glucuronidation, sulfonification, oxidation)
    • Heavy metal elimination – e.g. copper, zinc

Questions for Further Discussion
1. What are indications of liver failure?
2. What are indications for a liver transplant?
3. What nutritional changes need to be made for people with liver disease?
4. What are the fat-soluble vitamins?

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 this topic: Liver 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.

Teitelbaum JE. The Liver and Bile Ducts. Rudolph’s Pediatrics. Rudolph C, et.al. eds. McGraw-Hill. New York, NY. 2003;1473-1477.

Informed Health Online. How Does the Liver Work? Institute for Quality and Efficiency in Health Care. Available from the Internet at https://www.ncbi.nlm.nih.gov/books/NBK279393/ (rev. 8/22/16, cited 1/11/19).

Johns Hopkins Health Library. Liver: Anatomy and Functions. Available from the Internet at https://www.hopkinsmedicine.org/healthlibrary/conditions/liver_biliary_and_pancreatic_disorders/liver_anatomy_and_functions_85,P00676 (cited 1/11/19)

American Liver Foundation. Ways to love your liver. Available from the Internet at https://liverfoundation.org/25-ways-to-love-your-liver/ (rev. 8/4/17, cited 1/11/19).

American Liver Foundation. Your Liver. Available from the Internet at https://liverfoundation.org/for-patients/about-the-liver/ (cited 1/11/19).

MedlinePlus. Liver Diseases. National Library of MedicineAvailable from the Internet at https://medlineplus.gov/liverdiseases.html (rev. 10/28/18, cited 1/11/19).

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

How Long Does Fecal Shedding Occur for Oral Vaccines?

Patient Presentation
A 78-day-old female came to clinic because her mother was concerned that her stools were “diarrheal.” She was breastfed and her mother said that her stools were “always loose.” For the past 3 weeks her stools were more frequent (4-5 times/day) of loose, pudding-like stools without blood, mucous or changes in color. They were yellow in color, and not foul-smelling nor voluminous. Her mother was concerned because her mother was visiting from another country and had had diarrhea. The baby was feeding well and acting well otherwise. The past medical history showed she was a full-term, first-born infant without significant past medical history. She had received her regular well child care at 63 days of life and received all of her vaccinations including rotavirus vaccine.

The pertinent physical exam showed an interactive infant without distress. Her weight was increasing at 26 grams/day since her well child care visit. Her examination was normal. The fresh stool in the clinic appeared consistent with the mother’s description and looked normal to the pediatrician.

The diagnosis of a healthy infant with normal stools but exposure to a relative with diarrhea was made. The mother was quite concerned about the possibility of an infectious diarrhea transmitted from the grandmother, therefore a stool enteric panel was run. The laboratory evaluation was negative for any other infectious process except was positive for rotavirus. The pediatrician felt this was due to shedding of the rotavirus vaccine and not a cause of diarrhea. The parent was informed of the results and continued to monitor the infant at home.

Discussion
Vaccination has reduced infectious disease morbidity and mortality since its introduction. Vaccines can be given intramuscularly, subcutaneously or orally. Oral virus vaccines currently used in the US include rotavirus, cholera, typhoid and adenovirus. Adenovirus vaccine is used in military personnel. As these are attenuated viruses there is concern for household contacts who are immunocompromised who may inadvertently be exposed to the virus through fecal shedding. Additionally, there is a concern that the attenuated virus may mutate and revert back to its wild-form and potentially cause disease.

Injectable polio vaccine is used in the U.S. and oral polio vaccine (OPV) is not used. Wild type polio type 2 was officially eradicated in 2015, and type 3 has not been detected globally since 2012, leaving type 1 as the most common circulating type.

The World Health Organization states in May 2012 that “…at least one dose of inactivated poliomyelitis vaccine (IPV) should be introduced into all routine immunization programmes globally, and trivalent oral polio vaccines (tOPV) will be replaced with bivalent (bOPV) in all OPV-using countries. The global “OPV Switch” was successfully conducted worldwide in April 2016 – setting the stage for the eventual withdrawal of all OPV.”

Learning Point
In an Australian birth cohort study in 2017, rotavirus was detected in 9.6% of stool swabs. “Proportions of infants shedding RotaTeq after first, second and third vaccine doses were 87.0%, 57.4% and 47.3%, respectively,…” with median durations of 3 (range 1-8), 1.5 (1-3) and 1 (1-2) weeks respectively. Other studies cite similar time frames. Per the American Academy of Pediatrics RedBook® “Infants living in households with immunocompromised people can be immunized. Highly immunocompromised patients should avoid handling diapers of infants who have been vaccinated with rotavirus vaccine for 4 weeks after vaccination.”

Cholera vaccine (VaxChora®) is known for shedding for at least the first 7 days but length of shedding has not been determined.

In a 2005 study of oral typhoid vaccine, fecal shedding was not detected at 7 or greater days after vaccination.
The American Academy of Pediatrics RedBook® do not currently have recommendations regarding infants living in households with immunocompromised people for cholera and typhoid vaccine.

For wild polio the “[v]irus persists in the throat for approximately 1 to 2 weeks after onset of illness and is excreted in feces for 3 to 6 weeks. Patients potentially are contagious as long as fecal excretion persists. In recipients of OPV, virus also persists in the throat for 1 to 2 weeks and is excreted in feces for several weeks, although in rare cases excretion for more than 2 months can occur. ” “IPV is recommended for these [infants and others who have immunocompromised household contacts], and OPV should not be used. If OPV inadvertently is introduced into a household of an immunocompromised or HIV-infected person, close contact between the patient and the OPV recipient should be minimized for approximately 4 to 6 weeks after immunization.”

Questions for Further Discussion
1. How common is rotavirus infection and what problems does it cause?

2. What vaccine properties cause them to be given intramuscularly, subcutaneously or orally?

3. What other diseases are vaccines being developed for?

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: Immunization and Rotavirus Infections.

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.

Kirkpatrick BD, Tenney KM, Larsson CJ, O’Neill JP, Ventrone C, Bentley M, Upton A, Hindle Z, Fidler C, Kutzko D, Holdridge R, Lapointe C, Hamlet S, Chatfield SN.
The novel oral typhoid vaccine M01ZH09 is well tolerated and highly immunogenic in 2 vaccine presentations.
J Infect Dis. 2005 Aug 1;192(3):360-6.

Anderson EJ. Rotavirus vaccines: viral shedding and risk of transmission. Lancet Infect Dis. 2008 Oct;8(10):642-9.

Brenneman K, McDonald C, Kelly-Aehle SM, Roland KL, Curtiss R 3rd.
Use of RapidChek® SELECTTM Salmonella to detect shedding of live attenuated Salmonella enterica serovar Typhi vaccine strains. J Microbiol Methods. 2012 May;89(2):137-47.

Taniuchi M, Begum S Uddin MJ, Platts-Mills JA, Liu J, Kirkpatrick BD, et.al.
Following oral vaccination as measured by quantitative reverse transcription-PCR versus culture. J Clin Microbiol. 2015 Jan;53(1):206-11.

Vaxchora (Cholera vaccine, live, oral) prescribing information Redwood City, California: PaxFax, inc.: 2016.
Available from the Internet at: https://www.fda.gov/downloads/biologicsbloodvaccines/vaccines/approvedproducts/ucm506235.pdf

Mosley JF 2nd, Smith LL, Brantley P, Locke D, Como M.Vaxchora: The First FDA-Approved Cholera Vaccination in the United States. P T. 2017 Oct;42(10):638-640.

Famulare M, Selinger C, McCarthy KA, Eckhoff PA, Chabot-Couture G.
Assessing the stability of polio eradication after the withdrawal of oral polio vaccine. PLoS Biol. 2018 Apr 27;16(4):e2002468.

American Academy of Pediatrics. Cholera, In Kimberlin, DW, Brady, MT, Jackson, M, and Long SS. eds. Red Book: 2018-21 Report of the Committee on Infectious Diseases. 30th edit. Elk Grove Village, IL: American Academy of Pediatrics; 2018.
Available from the Internet at https://redbook.solutions.aap.org/chapter.aspx?sectionid=189640178&bookid=2205 (cited 1/11/19).

American Academy of Pediatrics. Polio, In Kimberlin, DW, Brady, MT, Jackson, M, and Long SS. eds. Red Book: 2018-21 Report of the Committee on Infectious Diseases. 30th edit. Elk Grove Village, IL: American Academy of Pediatrics; 2018.
Available from the Internet at https://redbook.solutions.aap.org/chapter.aspx?sectionid=88187218&bookid=1484 (cited 1/11/19).

American Academy of Pediatrics. Rotavirus, In Kimberlin, DW, Brady, MT, Jackson, M, and Long SS. eds. Red Book: 2018-21 Report of the Committee on Infectious Diseases. 30th edit. Elk Grove Village, IL: American Academy of Pediatrics; 2018.
Available from the Internet at https://redbook.solutions.aap.org/chapter.aspx?sectionid=189640175&bookid=2205 (cited 1/11/19).

American Academy of Pediatrics. Salmonella, In Kimberlin, DW, Brady, MT, Jackson, M,and Long SS. eds. Red Book: 2018-21 Report of the Committee on Infectious Diseases. 30th edit. Elk Grove Village, IL: American Academy of Pediatrics; 2018.
Available from the Internet at https://redbook.solutions.aap.org/chapter.aspx?sectionid=189640178&bookid=2205 (cited 1/11/19).

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