What Causes Microcephaly?

Patient Presentation
A 5-month-old male came to clinic for his health supervision visit and followup from his neonatal intensive care stay. He was born prematurely at 28 weeks gestation and his stay was complicated by a right sided Grade III intraventricular hemorrhage, a left-sided Grade IV intraventricular hemorrhage, neonatal seizures, respiratory distress and bronchopulmonary dysplasia, retinopathy of prematurity, acute kidney injury that had resolved, possible necrotizing enterocolitis incidents x 2, and herpes simplex encephalitis. He was on home oxygen, a nasogastric feeding tube because of aspiration risk and multiple medications. He was taken care of by his mother, maternal grandmother and home nursing. He was to start home physical therapy, and had multiple followup appointments for specialty care already arranged.

The pertinent physical exam showed a small infant with a nasal canula and feeding tube in place. Weight (= 4.116 kg) and height (=54 cm) were at the 3th percentile and tracking. Head circumference was < 3% and was 36 week gestation (=33 cm). Premature infant standard growth charts were used. He had a small head and was not responsive to the examiner but was to the mother's voice. Extraoccular movements and pupillary reflexes were intact. He was hypotonic but when he became agitated would have increased tone and rigidity. He had several beats of clonus.

The diagnosis of a former premature infant with multiple significant medical problems was made including microcephaly. The physician reviewed the overall care plan with the mother including addressing needs for transportation, medical supplies and respite care. The infant’s next health supervision visit for vaccines including influenza was coordinated with a specialty appointment.

Discussion
Microcephaly is usually defined as an occipitofrontal head circumference (OFC) more than 2 standard deviations (SD) below the mean for sex, age and ethnicity. Severe microcephaly is used for OFC < 3 standard deviations. Rates of microcephaly range from 0.5-12 patients/10,000 live births.

The OFC should be measured at every well child visit and at other opportunities and plotted on standard growth charts. The OFC is measured using a nonelastic tape measure around the largest part of the head with the tape measure held above the eyebrows and ears. It is a highly reproducible measurement. There are several different international standard growth charts that can be used and those used should reflect the population the patient is drawn from the best. For example, the World Health Organization has growth charts taken from the children in the countries of Brazil, Ghana, India, Oman and the USA (www.who.int/childgrowth/en). In industrialized countries the OFC is larger and may not be as accurately reflected using the WHO chart. Some researchers prefer the Centers for Disease Control growth charts as an industrialized country standard (www.cdc.gov/growthcharts/)

While the OFC reflects the skull size and growth over time, the main determinant of normal growth of the skull is the brain and therefore, the OFC is considered a marker of brain growth. However, the extent of the microcephaly does not significantly correlate with the degree of developmental delay.

There are different categorizations of microcephaly, but the authors of the largest study of microcephaly recommend using primary or secondary (i.e. noted at birth or after birth respectively) as this helps with timing of microcephaly onset and therefore possible underlying causes. Proportional (i.e. weight and height are also 2 SD below their means) vs disproportional (i.e. weight and height are 2 SD or more above their means) also helps with diagnostic reasoning and evaluation.

The phenotype of patients with microcephaly is variable and often reflects the underlying diagnosis and concomitant organ systems that are affected. Intellectual delay or disability is the most common problem associated with microcephaly but other problems do occur.

Learning Point
The differential diagnosis of microcephaly is heterogeneous and many causes are not identified. In the largest study of microcephaly (N=680), where causes could be identified, 38% were primary and 62% were secondary. More patients were male and the majority of children were identified with microcephaly by 7-8 months of age.

  • Known cause = 59%
    • Genetic 28.5%
    • Perinatal brain injury 26.7%
    • Craniosynostosis 2.1%
    • Post natal brain injury 1.9%
  • Unknown cause = 40.7

In Brazil in March 2015, Zika virus became identified as a likely cause of primary microcephaly and an emerging, urgent public health concern, although the virus was identified in 1947.

The differential diagnosis of microcephaly includes:

  • Craniosynostosis
  • Genetic
    • Chromosomal problems
      • Trisomy 13, 18, 21
      • Williams syndrome
    • Monogenetic problems (including named and unnamed syndromes/mutations)
      • Autosomal dominant microcephaly
      • Autosomal recessive microcephaly
      • X-chromosomal microcephaly
      • Aicardi-Goutrieres syndrome
      • Ataxia-telangectasis
      • Borgeson-Forssman-Lahman syndrome
      • Cockayne syndrome
      • Cohen syndrome
      • Cornelia de Lange syndrome
      • Ligase IV syndrome
      • Marden syndrome
      • Mowat-Wilson syndrome
      • Feingold Syndrome
      • Rett Syndrome
      • Rubeinstein-Taybi syndrome
      • Smith-Lemli-Opitz syndrome
      • Seckel syndrome
      • Various other gene mutations
    • Imprinting disorders
      • Angleman syndrome
  • Infections (intrauterine, peri- or post-natal)
    • Encephalitis
    • Meningitis
    • Cytomegalovirus
    • Herpes simplex
    • HIV
    • Rubella
    • Syphilis
    • Toxoplasmosis
    • Varicella
    • Zika virus
  • Intrauterine event or problem
    • Death of twin
    • Placental insufficiency – extreme
    • Vascular incident such as stroke
  • Maternal disease
    • Anorexia nervosa
    • Hyperphenylalanenaemia
  • Metabolic causes
    • Cobalamin metabolism diorders
    • Galactosemia
    • Glycine encephalopathy
    • Glycose transporter defect
    • Glycosylation syndome
    • Leukodystrophies
    • Lysosomal storage disorders
    • Menkes disease
    • Mitochrondrial disorders
      • Pyruvate dehydraogenase deficiency
    • Molybdenum cofactor deficiency and sulphite oxidase deficiency
    • Neuronal ceroid-lipofuscinosis
    • Organic aciduria
    • Peroxisomal disorders
    • Phenylkeonuria
    • Purine and pyramidiaine metabolism disorders
    • Serine biosynthesis disorder
    • Sterol biosynthesis disorder
    • Urea cycle defects
  • Perinatal brain damage
    • Hypoxic-ischemic encephalopathy
    • Vascular event – hemorrhage or thrombosis
  • Structural brain abnormalities
    • Anencephaly
    • Holoprosencephaly
  • Teratogens
    • Alcohol
    • Antiepileptic drugs
    • Cocaine
    • Lead
    • Mercury
    • Radiation
    • Uremia
  • Trauma
    • Accident
    • Child maltreatment
    • Psychosocial deprivation
  • Other
    • Malnutrition
      • B12 deficiency
    • Systemic disorders
      • Congenital heart disease
      • Hypothyroidism
      • Hypopituitarism

Note that many of other disorders may have a genetic cause

Questions for Further Discussion
1. What are potential treatments to help children with microcephaly?
2. What are indications for radiographic imaging for microcephaly and which modalities are best used?

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, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Brain Malformations, Zika Virus, and Developmental Disabilities.

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.

von der Hagen M, Pivarcsi M, Liebe J, et.al. Diagnostic approach to microcephaly in childhood: a two-center study and review of the literature. Dev Med Child Neurol. 2014 Aug;56(8):732-41.

Harris SR. Measuring head circumference: Update on infant microcephaly. Can Fam Physician. 2015 Aug;61(8):680-4.

White MK, Wollebo HS, David Beckham J, Tyler KL, Khalili K. Zika virus: An emergent neuropathological agent. Ann Neurol. 2016 Oct;80(4):479-89.

Hansen M, Armstrong PK, Bower C, Baynam GS. Prevalence of microcephaly in an Australian population-based birth defects register, 1980-2015. Med J Aust. 2017 May 1;206(8):351-356.

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

In Airway Emergencies Always Start With The Basics of Airway Management

We have just finished another round of Critical Event Training for my hospital’s Anesthesia and OR staff. One of the scenarios we ran was how to manage a failed airway: the dreaded “can’t intubate-can’t ventilate” scenario.

As an instructor, it’s important for me to set the stage realistically. The more real the scenario, the more the providers will learn and be able to apply the information should they ever find themselves in a comparable situation. I must observe as the trainees respond to the emergency, and then help the trainees self-analyze what went well — or not so well — during the scenario. Of course, discussion of how things went during a training scenario always leads to sharing of examples from past real life scenarios. And after 37 years of practice I’ve had a lot of sharable experiences.

One past case we discussed is particularly appropriate for those students around the country who are just beginning to learn airway management because the solution rested in basic airway management techniques. All illustrations from Anyone Can Intubate 5th Edition.

Case

The patient was a 50 yo, 5’ 10”, 110 kg male suffering from respiratory failure from sepsis. The intensivist was preparing to intubate  and had asked me, as the anesthesiologist on the code team that day, to come over to the ICU to provide an extra pair of hands in case the intubation proved difficult. However, as I entered the ICU it was clear that the situation had clearly changed for the worse. The intensivist had tried and failed the intubation and had then been unable to ventilate. He was just setting up for an emergent cricothyrotomy. The oxygen saturation was 50. A nurse was unsuccessfully attempting to ventilate the unresponsive patient.

I had brought a glidescope with me and I rushed to the head of the bed, intending to attempt another intubation to establish an airway. However, the first thing I saw was that the nurse, in her anxiety, was pushing the face mask down over the face and in the process, forcing the chin down over the neck. The whole head was bent steeply downward.

I quickly took over the airway, tilted the head back into the sniffing position and inserted an oral airway. I grabbed both jaw angles and pulled upward. The patient had a large round face and a thick neck which made keeping the mask seal challenging with one hand. I instead made the seal with both hands and asked the nurse to squeeze the bag. We were immediately able to ventilate and the saturation rose over the next minute into the mid 90s. Everyone in the room took a deep breath. I was then able to intubate using the Glidescope. Disaster was averted.

In this particular airway emergency, the lesson learned was to always start with the basics of airway management. Links are provided below to previous blog articles with greater detail on each topic. I recommend reading to the end for the big picture and then returning to the links for more in depth discussions.

Don’t Be Afraid To Ask For Help

Our intensivist called for assistance early.  Rarely will you be in a situation where you are the only person trained in intubation. Never hesitate to ask for help. That help can be getting equipment ready, aid in holding the head or neck in position, or asking someone else to intubate.

The faster that help can arrive, the better off you (and your patient) are. Ask early and apologize later if you don’t need the help. If I’m anticipating a potentially difficult intubation I will often ask a colleague to stand by as an extra pair of hands. I also make sure I have back up equipment like bougies, supraglottic airways, and videolaryngoscopy.

Can’t Intubate

A common error if you’re having trouble intubating is to keep trying the same thing over and over again. Change your blade from a curved MAC to a straight Miller blade or the reverse. Alter the patient’s head position, try cricoid pressure, have someone else try. Sometimes it’s your technique that’s making the intubation difficult.

Bear in mind, however, that the more laryngoscopies you perform, the more likelihood there is of increasing laryngeal edema or bleeding. This can worsen the airway and ultimately make ventilation difficult. Unless you quickly see evidence of impending success, it’s often better to switch to an alternative method of intubation like videolaryngoscopy when you can.

Of course, if the intubation is elective, such as for elective surgery, then you can always abort the intubation attempt and awaken the patient to perform an awake intubation.

Can’t Ventilate

This is a true emergency. Without the ability to ventilate, you have only minutes until life-threatening complications occur, including brain damage and death. You must always be prepared for loss of the airway because it can occur unexpectantly.

First, Open the Airway

The most common cause of airway obstruction is the collapse of tongue and soft tissue at the back of the throat over the larynx. Tilting the head and pulling the jaw upward lifts this tissue off the larynx and opens the airway.

A common cause of airway obstruction is the collapse of tongue and soft tissue at the back of the throat over the larynx. Tilting the head and pulling the jaw upward lifts this tissue off the larynx and opens the airway.

A common cause of airway obstruction is the collapse of tongue and soft tissue at the back of the throat over the larynx. Tilting the head and pulling the jaw upward lifts this tissue off the larynx and opens the airway.

Use the head tilt, chin lift maneuver or the triple airway maneuver. Even if you’re using cervical spine precautions (and keeping the head in a neutral position with the neck) you should still pull the jaw upward.These maneuvers lift the tongue, epiglottis and soft tissue upward and off the glottic opening.

The triple airway maneuver tilts the head, lifts the chin, and thrusts the jaw.

The triple airway maneuver tilts the head, lifts the chin, and thrusts the jaw.

Insert An Oral or Nasal Airway

Insert an nasal or an oral airway to treat airway obstruction. Nasal airways are better tolerated by semi-conscious patients. Oral airways are often used in unconscious patients to avoid the potential risk of nose bleed.

Always insert a nasal airway parallel to the floor of the nose.

Always insert a nasal airway parallel to the floor of the nose.

You can use a tongue blade to pull the tongue forward and then slide the oral airway in over the tongue to keep the tongue off the larynx.

You can use a tongue blade to pull the tongue forward and then slide the oral airway in over the tongue to keep the tongue off the larynx.

Oral and nasal airways are not mutually exclusive. If I’m having a really hard time ventilating a patient I will insert both an oral and a nasal airway. They work by different mechanisms and their function ca be additive. If the patient regains consciousness, and a gag reflex, to the extent that they are no longer tolerating the oral airway then you may have to remove it. Having a nasal airway in place helps maintain an airway that may still be somewhat precarious.

Pull The Face Into The Mask,
Never Push The Mask Onto The Face

A big mistake with ventilation is trying to seal the mask by pushing the mask down onto the face, as in this case. This maneuver invariably forces the chin downward, piling the soft tissue around the back of the tongue over the larynx and worsening airway obstruction.

The first step to a good mask seal is opening the airway.

The first step to a good mask seal is opening the airway. (All illustrations from Anyone Can Intubate 5th Ed., C. written MD)

To ventilate, start with a good mask seal. Always pull the face up into the mask by grasping the mandibular bone (not the soft tissue) and lifting the face into the mask to produce the seal. The face becomes sandwiched between your fingers pulling up and your thumb and forefinger sealing the mask against the face.

 

 

 

 

Apply the top of the mask to the bridge of the nose, where leaks often occur.

Apply the top of the mask to the bridge of the nose, where leaks often occur.

Pull the face into the mask, using the cheek tissue on either side to help make the seal.

Pull the face into the mask, using the cheek tissue on either side to help make the seal.

Seat the mask over the chin, making sure the lower lip is inside the mask.

Seat the mask over the chin, making sure the lower lip is inside the mask.

Note the finger positions. Thumb and forefinger press mask against the face and form a "C" shape. Remaining fingers grip mandible and form an "E".

Note the finger positions. Thumb and forefinger press mask against the face and form a “C” shape. Remaining fingers grip mandible and form an “E”.

 

Note the positions of the fingers. Thumb and forefinger press mask against the face and form a “C” shape. Remaining fingers grip mandible and form an “E”. You are literally pulling the face into the face with your fingers while your thumb is applying counter pressure. This push pull action also holds the head in extension and holds the airway open.

 

Don't just push the mask down, pull the patient's face into the mask t seal.

Don’t just push the mask down, pull the patient’s face into the mask to seal.

Use Two Person Ventilation When It’s Hard To Ventilate

Use good ventilation technique, based on your knowledge of basic physiology, to ventilate effectively, as previously discussed in this blog article.

If difficulty persists, use both your hands to seal the mask. Have a helper squeeze the bag for you. Place thumbs on top of the mask, index fingers on the bottom, bunching the soft tissue of the cheeks under the mask. Pull the jaw upward with your remaining fingers by spreading them along the jaw line, underneath the angle of the mandible. Pull up forcefully, squeezing the patient’s face between the mask and your hands. Hold just the bone. Pushing on the soft tissue under the jaw can force it into the airway and worsen obstruction.

Using both your hand to seal a mask is very efficient in long difficult ventilations. You must communicate carefully with the assistant squeezing the bag to ensure good ventilation.

Using both your hand to seal a mask is very efficient in long difficult ventilations. You must communicate carefully with the assistant squeezing the bag to ensure good ventilation.

Use of both hands makes it easier to shift the mandible forward and pull the obstructing tissue up and off the larynx. Move your fingers as needed to perfect your seal. You may still sometimes need a helper to stop leaks

When someone else is squeezing the bag, it’s especially important to verify adequate ventilation — since you can no longer feel the compliance of the bag yourself. Watch the chest rise, see the air condense on the mask (if mask is clear plastic), and have someone listen for breath sounds. Make sure your helper communicates any signs of obstruction or lack of seal immediately. This technique is a team effort.

Follow this link to a video on how to open an airway, insert an oral or nasal airway and apply a mask to ventilate. Ventilation using both one hand and two hands with an assistant is also demonstrated.  

Supraglottic Airways

If the goal is urgent ventilation, remember that intubation is only one way to ventilate.  Consider changing to an alternate method of ventilation, such as use of a supraglottic airway like the Laryngeal Mask Airway . If you can ventilate though an LMA you will have time to consider what further steps need to be taken to secure the airway.

In you still can’t ventilate, you must consider surgical options such as a jet ventilator or cricothyrotomy to quickly reestablish oxygenation. The intensivist was just beginning this step when I arrived on the scene.

Failed Airway Algorithm

A Failed Airway Algorithm

Crisis Management

In the stress and chaos of an emergency, it’s a common human failing that the brain can freeze in unfamiliar circumstances. Forgetting key steps and even techniques is common. That’s one of the main reasons why we perform Critical Event Training. It’s also the reason we all have to rectify with ACLS, PALS, BLS every 2 years. It’s easy to forget the basics if you don’t use them all the time.

The more familiar we are with a scenario, the more likely we will immediately perform the steps that are needed to resolve it, especially if those crises are rare in real life. In addition, Crisis Check Lists are increasingly being used to specifically help ensure that providers use all possible options during rare critical events such as cardiac arrests, pulmonary emboli, dysrhythmias, hypoxia, and others. If your hospital doesn’t have Crisis checklists consider obtaining them.  One such aide can be downloaded here.

Teamwork is also extremely important. Your team members must feel comfortable with making suggestions, pointing out potential problems, and keeping each other informed on what steps have been taken and which are needed. The value of treating patients as a team is that you can leverage the power of multiple brains in the room to solve the problem. You are much more powerful and likely to succeed as a group rather than trying to act alone.

Frequent practice, learning about how to treat those rare emergencies, and improving your ability to function as a team is important before you actually find yourself in a critical event.

May The Force Be With You

Christine Whitten MD

Author, Anyone Can Intubate 5th Edition.

 

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Filed under: Airway Management, Airway obstruction, Anesthesia, can’t intubate can’t ventilate, complications of intubation, Difficult Intubation, Emergency airway management, Glidescope, Intubation, Laryngeal Mask Airways, Ventilation With Bag-Valve-Mask, Videolaryngoscopy Tagged: can’t intubate can’t ventilate, failed intubation, how to apply a ventilation mask, how to open an airway, how to ventilate a patient, nasal airway, oral airway, ventilation

Trust me, I’m a GP

Here at DFTB we are keen to promote a culture that breaks down the silos of who can do what. We all care about one thing, above all else, the wellbeing of the children we treat. Working in a hospital environment sometimes gives us a skewed view of illness. Just like every neurosurgeon that sees a patient with a headache is concerned about a sub-arachnoid haemorrhage, every doctor in the paediatric emergency department is concerned about missing sepsis.

With winter (in the south) dragging on, we are seeing more and more children in the emergency department. It has become so bad that some hospitals are even sending out tweets suggesting patients get taken elsewhere. Why not their general practitioner?

Today I’m going to take a look at the following paper and its controversial conclusions.

Freed GL, Spike N, O’Hara J, Hiscock H, Rhodes AL. National study of parental confidence in general practitioners. Journal of Paediatrics and Child Health. 2017 Sep 3.

 

How was it performed?

A representative sample of 2100 Australians  completed an online survey. They had to act as caregivers for a child under the age of 17, live in Australia and have internet access. This sample group was taken from a larger research panel of over 120,000 Australians and was distributed across the states in proportion to the population. The survey was anonymous and incentivized to improve completion rates.

 

What were the results?

Whilst there are days when I think every child in the neighbourhood has been brought to our ED the survey results suggest that a whopping 93% of caregivers take their child to the GP.

Putting that in perspective it means that if, in a 10 hour shift, I see 8 children with a cough, cold or runny nose that I think could have gone to to their GP another 194 are being cared for by general practitioners.

But were the parents happy with the advice they received? 

When it comes to minor illness 89% (1884 of 2100) respondents were either mostly or completely confident in the health care provider. A similar number (89%) were also confident that their GP could handle a minor injury or two.

So what did the authors conclude?

The authors concluded that fewer than 44% of parents expressed complete confidence in their GP in dealing with general health issues for their child. A regression analysis revealed that lower levels of confidence were associated with younger parents and a higher level of attained education whereas increased confidence was associated with older parents and visiting a regular GP.

What has the media said?

A clickbait ad-driven press reads the abstract and misses the raw data. Table 2 (reprinted above) clearly states that only 4% of parents bypass their GP’s and go straight to the ED.

What do I think?

Whilst I think the paper asks some interesting questions I would reframe the conclusion around the fact that 89% of parents are mostly confident that their GP knows what they are doing. Freed et al. argue the semantics of the term complete confidence suggesting that parents who are not completely confident might be more inclined to present to the emergency department I would like to know the baseline level of complete confidence in all doctors.  

There has been an increase in the number of children presenting to the ED and it is important to drill down and find out why, especially when so-called low acuity cases are on the rise. An earlier survey, carried out by Freed, of four metropolitan hospitals in Victoria (one of which was a tertiary paediatric centre) showed that only 43% of parents had attempted to make an appointment with a GP prior to attendance. When asked why they went to hospital it seemed that the majority (94%) of the parents felt that their child had a serious condition. There is clearly a disconnect between what a parent thinks is serious (and thus warrants hospital attention) and what a triage nurse or treating doctor thinks is not serious (and thus should have gone to the GP).

Borland et al. also point out some possible inconsistencies with the use of triage category as a surrogate marker for acuity. A child with persistent bruising and lethargy may be given a triage category of 4 or 5 marking them as low acuity but their underlying diagnosis of leukaemia would never be classified as low acuity. Triage categories provide arbitrary time based targets in which patients should be seen and may not reflect the underlying seriousness of their condition. If you look at the Australian Institute of Health and Welfare (AIHW) definition of a low acuity GP-type patient you can see the problem…

….as one who did not arrive by ambulance/police/correctional vehicle, was not admitted, had a triage category 4 or 5, was not referred to another hospital and did not die.

What none of the papers provide is outcome data. I would be interested to know what exactly the themes across the low-acuity presentations were and what were the outcomes of those visits in terms of processes that cannot be readily performed in a busy general practice (blood tests, radiographs, ultrasounds) and admissions.

Other studies of child attendances also highlight that one of the major drivers for attendance is not lack of confidence but parental perceived seriousness. How one changes a culture is then up for debate.

References

Freed GL, Spike N, O’Hara J, Hiscock H, Rhodes AL. National study of parental confidence in general practitioners. Journal of Paediatrics and Child Health. 2017 Sep 3.

Freed GL, Allen AR, Turbitt E, Nicolas C, Oakley E. Parent perspectives and reasons for lower urgency paediatric presentations to emergency departments. Emergency Medicine Australasia. 2016 Apr 1;28(2):211-5.

Turbitt E, Freed GL. Paediatric emergency department referrals from primary care. Australian Health Review. 2016 Dec 21;40(6):691-5.

Borland M, Skarin D, Nagree Y. Comparison of methods used to quantify general practice‐type patients in the emergency department: A tertiary paediatric perspective. Emergency Medicine Australasia. 2017 Feb 1;29(1):77-82.

Cheek JA, Braitberg G, Craig S, West A. Why do children present to emergency departments? Exploring motivators and measures of presentation appropriateness for children presenting to a paediatric emergency department. Journal of Paediatrics and Child Health. 2017 May 1;53(5):451-7.