A 3-day-old neonate presents to the ED with a 1-day history of episodes of abnormal left arm movements associated with perioral cyanosis, ‘staring’ with eyes deviating to the left and ‘lipsmacking’. The episodes last a few minutes in duration. The baby was born at 35 weeks via emergency caesarean section and Apgar scores of 4 and 8, with a birth weight of 2.4 kg. Clinically the child is a sleepy neonate with mild hypotonia, brisk reflexes and normal vital signs with a blood sugar level of 3.1. No evidence of sepsis is present.
Which ONE of the following is the BEST answer?
Answer: B: This child presents with combination of subtle seizures and myoclonic seizures. Five seizure types are common in neonates: subtle, tonic, clonic, spasms and myoclonic. Often there is no EEG seizure correlation with the clinical picture. It is rare for neonates to have GTC seizures, as the immature neonatal central nervous system (CNS) is unable to sustain such neurological activity. ‘Subtle’ seizures are much more common and include chewing, lip smacking, bicycling, eye deviation or blinking – these are usually not correlated on an EEG. Myoclonic seizures are rapid jerking, single or repetitive, and suggest severe underlying pathology. Tonic seizures – focal or generalized with sustained tonic activity – are often due to HIE in neonates. Clonic seizures – focal or multifocal – with rhythmic jerking of limb or limbs often relate to metabolic abnormality such as hypoglycemia. Spasms are sudden generalized jerks lasting 1–2 seconds that are distinguished from generalized tonic spells by their shorter duration. The above clinical picture suggests a hypoxic perinatal event in an at-risk population (premature, low birth weight with initial low Apgar score). HIE is a common complication of premature births. HIE is the cause of 50–60% of all neonatal seizures, with perinatal asphyxia the most common mechanism causing HIE in neonates. At birth, these infants may be depressed and may fail to breathe spontaneously. In the ensuing hours, they remain hypotonic or change from a hypotonic to a hypertonic state, or their tone may appear normal. Hypotonia, lethargy and decreased spontaneous movements are classic signs. Upper motor neuron (UMN) brisk tendon reflexes and hypotonia are hallmarks of this condition.
Intracranial haemorrrhage is the second most common cause of neonatal seizures. Intracerebral haemorrhage is often related to prematurity, while subdural haematoma and subarachnoid haemorrhage are associated with term babies and birth trauma or non-accidental injury (NAI). The obvious complication to rule out in this setting is birth trauma with intracranial haemorrhage – a head ultrasound followed by definitive brain CT is indicated. NAI with subdural or extradural haemorrhage is another important differential to consider.
Meningitis is a possible diagnosis in this scenario, but the absence of fever is against this as the likeliest diagnosis. After a head CT has excluded focal pathology, an LP is indicated. Additionally, any of the antenatal or peripartum infectious agents included in the TORCHES infections (toxoplasmosis, rubella, CMV, herpes and syphillis) may cause seizures in the neonate and a full septic work-up is always indicated. While hypoglycaemia can cause seizures, the BSL of 3.1 is not classified as hypoglycaemia requiring correction. A sugar <2.7mmol/L would require 5 mL/ kg 10% dextrose as an immediate IV bolus. Other causes of seizures include hypocalcaemia, hypomagnesemia, hypo- or hypernatraemia, kernicterus, inborn errors of metabolism, mitochondrial defects and pyridoxine dependency, which may respond to a trial of pyridoxine and drug withdrawal syndromes related to narcotic or amphetamine abusing mothers.
Reference:
A 3-day-old neonate presents to the ED with ongoing intermittent episodes of seizures despite an initial dose of buccal midazolam given in the ED. His organic work-up is completely normal and all reversible causes have been excluded.
Which ONE of the following is CORRECT regarding his subsequent management?
Answer: C There is some disagreement in the literature, and also within paediatric neurology circles, about which is the anticonvulsant of choice in status epilepticus in neonates. A suggested regime is as follows.
1- Initial seizure termination: Lorazepam 0.05 mg/kg IV can be used either as the initial drug or as second-line treatment in a newborn who did not respond to treatment with phenobarbital and phenytoin. The anticonvulsant effect is seen within 5 minutes and the effect can last 6–24 hours. It does not usually cause hypotension or respiratory depression.
2- Second dose of benzodiazepine:
3- Phenobarbitone 10–20 mg /kg IV – traditionally considered by many to be the drug of first choice in neonatal seizures.
4- Phenytoin 15–20 mg/kg, although kinetics very difficult to predict in neonates. If a total loading dose of 40 mg/kg of phenobarbital is not effective, then a loading dose of 15–20 mg/kg of phenytoin can be administered intravenously. The rate must not exceed 0.5–1 mg/kg/min in order to prevent cardiac problems. Phenytoin should not be mixed with dextrose solutions. Owing to its reduced solubility, potentially severe local cutaneous reactions, interaction with other drugs and possible cardiac toxicity, intravenous phenytoin is not widely used.
Consideration of novel drugs in discussion with paediatric neurology. Topiramate and levetiracetam have been reported to be the drugs of second and third choice for many paediatric neurologists. Further studies are needed to confirm efficacy and safety profiles in neonates.
5- Trial of IV pyridoxine. Pyridoxine dependency, a rare, inherited autosomal recessive disorder, must be considered when generalized clonic seizures begin shortly after birth with signs of fetal distress in utero. These seizures are particularly resistant to conventional anticonvulsants such as phenobarbital or phenytoin. When pyridoxinedependent seizures are suspected, pyridoxine or pyridoxal phosphate should be administered intravenously, ideally during the performance of an EEG. The seizures abruptly cease, and the EEG normalizes in the next few hours. Some cases of pyridoxine dependency do not respond dramatically to the initial bolus of IV pyridoxine. Therefore, a 6-week trial of oral pyridoxine or preferably pyridoxal phosphate is recommended for infants in whom a high index of suspicion is present.
A 2-year-old girl presents with a glucose of 25 mmol/L and a history of polydipsia. Her urine shows ketonuria. Her vital signs are: HR 100; RR 42; BP 90/65; saturation 98%; temperature 38° C. Her CRT is 3s and she appears alert but tired. Her mucous membranes and lips appear dry, her eyes are not sunken, she is producing tears and her skin turgor is normal. She has features suggestive of an upper respiratory tract infection (URTI).
Answer: B: This child has features suggesting a diagnosis of DKA in the setting of an intercurrent upper respiratory tract infection. Her vital signs are not suggestive for shock, but rather support the likelihood of acidosis; increased respiratory rate due to compensatory respiratory alkalosis, and a delayed capillary refill, which accompanies acidosis. She has some features of dehydration, likely due to her osmotic diuresis.
The biochemical criteria for the diagnosis of DKA include:
Fluid management in DKA in children is always balanced against their increased risk of cerebral oedema. Cerebral oedema may develop as a complication of the disease process as well as the theoretical pathogenesis due to the rapid administration or excessive volume of fluid. For this reason, fluid deficit and maintenance is replaced over 48 hours. There is currently a strong trend away from bolus fluid management in children with DKA, unless shock is evident, in which case caution is advised when administering a fluid bolus, and the current recommendation is not to exceed a bolus of 20 mL/kg (without prior consultation with an intensivist or paediatric endocrinologist).
Urine output is a poor marker of good renal perfusion due to the profound osmotic diuresis present anyway, which once more makes estimation of fluid requirements in DKA challenging.
Regarding the development of cerebral oedema in the setting of DKA, which ONE of the following is INCORRECT?
Answer: A: Although poorly understood, the risk factors for cerebral oedema in DKA include presentation with new onset type 1 diabetes, younger age, elevated serum urea nitrogen and/or severity of dehydration at presentation, severity of acidosis, greater hypocapnia at presentation (after adjusting for degree of acidosis) and an attenuated rise in serum sodium during treatment for DKA. Bicarbonate treatment to correct acidosis has also been associated with cerebral oedema, but whether this is due to a de novo effect, or simply a reflection of the severity of DKA, is unclear.
The use of hypotonic fluids, however, is associated with greater rises in intracranial pressure compared with isotonic fluids. Therefore, the use of solutions with salt content <0.45% NaCl, which contain a large amount of electrolyte-free water, is likely to lead to a rapid osmolar change, movement of fluid into the intracellular fluid (ICF) compartment and may increase the risk of cerebral oedema. The failure of the serum sodium to rise or development of hyponatraemia during intravenous fluid administration has been shown to precede cerebral oedema.
References:
Regarding DKA in children, which ONE of the following is FALSE?
Answer: C: Factors associated with DKA in children with newly diagnosed type 1 diabetes include younger age (those aged <5 years are at greatest risk), children with a first degree relative with type 1 diabetes, and those from families of lower socioeconomic status. High-dose glucocorticoids, antipsychotics, diazoxide and immunosuppressive drugs have been reported to precipitate DKA in individuals not previously diagnosed with type 1 diabetes. The risk of DKA in established type 1 diabetes is increased in children and young people with poor metabolic control or previous episodes of DKA.
The most common precipitating factors in the development of DKA include infection, often as a result of inadequate insulin therapy during intercurrent illness and insulin omission. Adolescent girls, children with psychiatric disorders (e.g. eating disorders) and those from families of lower socioeconomic status are also at increased risk. DKA is rare in children whose insulin is administered by a responsible adult. Insulin should be commenced after fluid rehydration has commenced. Administration of intravenous fluid prior to insulin results in substantial falls in blood glucose, because the resultant increase in glomerular filtration rate (GFR) leads to increased urinary glucose excretion. The aims of fluid and sodium replacement therapy in DKA are:
Following initial resuscitation (if required), subsequent fluid management should be with 0.9% saline. If hypernatraemia is present, consider the use of 0.45% saline.
Abdominal pain may be a prominent complaint in children experiencing DKA. The abdominal pain may be severe enough to mimic an acute ‘surgical abdomen’. The exact cause of the abdominal pain associated with DKA is not known. One theory involves prostaglandins. Prostaglandins I2 and E2, which are generated in adipose tissue, are increased during DKA.
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