History and Examination
Often, parents seek medical advice simply because the infant exhibits generalized irritability, failure to thrive, and, rarely, unexplained vomiting. A complete clinical history should be obtained to include:
- Neonatal history: Relevant antenatal/birth history including gestational age at time of birth, birth weight, and head circumference
- Family history: Relevant sibling or parental history
- Head circumference: Head circumference should be corrected for gestational age and plotted on a centile chart with previous measurements, if available. Transcentile growth should alert the need for further investigation by imaging.
- Weight: Weight should be plotted on centile chart as a comparator to head circumference. This will alert the management team to slowed growth and malnutrition resulting from the tumor effect. It will also be helpful for calculations of drug doses, fluid requirements, and the like.
- Fontanelle: The size and appearance of the fontanelle should be recorded.
- Eye examination: The pupillary light reflex, pupillary red reflex (patients with retinal neuroblastoma lose the normal reflective red reflex), and extraocular movements should be checked.
- Muscle tone: Normal tone is expected. Hypertonia is identified as in the older child. Hypotonia is suspected with head lag (when the infant is lifted by the hands to a sitting position, the head should flex to follow the motion and hold momentarily), slip-through on upright suspension (infants held under the axillae will usually support themselves), and ‘rag-doll’ on ventral suspension (infant placed prone on the examiner’s hand will usually extend the back, flex the arms and knees, extend the hips, and rotate the head), and complete supine abduction of the hips is abnormal with respect to muscle tone.
- Motor development: The child’s motor developmental milestones dates should be recorded. By 12 weeks an infant should lie supine with the head in the midline, wave the hands symmetrically, and lift the head and the upper chest when in prone position. At 6–8 months gross motor development should include sitting without support, rolling over, and lifting the chest off prone position by arm extension. At 9–10 months the child should sit alone, turn to look, support weight when suspended, and beginning to ‘hold on’. Motor development at 12 months is quite variable. Some children will ‘cruise’ around furniture by holding on in a standing posture. Independent walking is expected by 18 months.
- CBC and serum electrolytes: A normal profile is expected unless there is prolonged vomiting.
- Coagulation profile: Usually not necessary unless there is a family history of bleeding diathesis or infant history such as term IVH.
- Blood gases: Arterial blood gas measurement is not usually necessary, although it may be helpful to identify pH and acid-base disturbance in the child with prolonged vomiting (remember other causes such as pyloric stenosis).
- Type and screen: Blood type and screen is done for all patients. A cross-match should be considered if there is the possibility for needing a blood transfusion or local factors anticipating delay in delivery of cross-matched blood if required urgently.
- Urine catecholamines: Estimation of urinary catecholamines will support a diagnosis of neuroblastoma.
- Screening examination: Detail may be suboptimal for a neoplastic diagnosis. Therefore, at some stage in the early assessment of macrocephaly, a cranial ultrasound should be supplemented by another modality of imaging such as CT or MRI to exclude other etiological factors.
- Screening examination that avoids sedation: A CT scan is often required to assist in confirming the presence of a suspected tumor. CT scanning is often more readily available than MRI, and fast imaging times may allow scans without the need for anesthesia or sedation. Since CT scans do entail exposure to radiation, many now choose to use MRI instead when possible.
- Special requirements because of age: In the first few weeks of life, it may be possible to obtain MRI of the infant by a “feed and wrap” technique, but most often general anesthesia is required. It is important to remember spinal imaging as a baseline preoperatively.
Nuclear Medicine Tests
- Radionucleotide scans: Radioisotope imaging (123I-MIBG) will supplement axial CT and MRI. If urine catecholamines are positive, positive imaging will secure the diagnosis of neuroblastoma.
- EEG of limited use: EEG can localize tumor laterality but is of limited diagnostic value.
- Evoked potentials of possible use for confirming intact pathways: Visual evoked responses (VER) may assist in the evaluation of integrity of the opticocortical pathway when visual field assessment is impossible. Brainstem auditory evoked responses (BSAER) may assist in evaluation of the integrity of the auditory pathway.
- Not usually used: Most neuropsychological tests are not applicable to infants given the complexity of interaction required. The Bayley-III® Scale of Infant and Toddler Development, however, does have an infant assessment tool, testing the five modalities of adaptive behavior, language, cognitive, motor, and social-emotional skill.
Correlation of Tests
- Timing of intervention determined by presentation: Evaluation of the clinical presentation, rapidity of symptom progression, and stability of the infant will determine the urgency of neurosurgical intervention. Diagnostic confidence with neuroradiology may allow initial conservative management if appropriate, thereby allowing maturation of the developing brain and an increase in circulating blood volume before surgical intervention.