Common problem in children, as well as adults!
Distinguish primary from secondary.
Most headaches get worse with exertion so that’s not a discriminating feature. Headaches that get worse on standing suggest a CSF leak; worse on lying down suggests a tumour. See NICE CKS.
International Headache Society 2004 Migraine without aura def:
Aura – Hemianopia or spreading scintillating scotoma. Note that migraine with aura is a contraindication to treatment with combined oral contraceptives.
Some specific types:
Neuronovascular condition – baseline hyperexcitability in cortex.
Double the risk if you had infant colic, which is not true for tension headache! Sleep disruption as common factor? [JAMA 2013;309:1607-12]
Several genetic links found eg C677T mutation of the methylenetetrahydrofolate reductase gene (MTHFR), EAAT2. [J Headache Pain. Jan 2012; 13(1): 1–9. doi: 10.1007/s10194-011-0399-0]
Beware Occipital epilepsy!
American Academy of Neurology recommendations are that neuroimaging should be considered in:
[CurrOpPeds Dec 2004]
Although popular perception is that migraine is caused or at least triggered by dietary factors, there is a wide variation in reporting of dietary triggers. Certainly migraine is associated with obesity, and dietary habits seem to be as important as specific foods, and there is probably a cycle of inconsistent nutrition and poor control of migraine.
My colleagues talk about 4Cs (chocolate, cheese, coffee, citrus) but I have found no evidence for this. Awareness of possibility of dietary triggers actually has greater influence on perception of personal triggers than personal experience! See below.
Some evidence for lipid intake esp PUFA (decreased ingestion of lipids was associated with a decrease in the frequency, intensity, and duration of migraines and a decrease in the use of medication) but confounded by obesity, weight reduction, and changes in nutrient intake. Another study found reduced migraine spells among children subjected to a diet rich in fibre. Not much evidence for cheese at all! [Nutrition Reviews. 70(6):337-56, 2012 Jun. UI: 22646127]
Trial of cyanocobalamin, folate, and pyridoxine (2 mg of folic acid, 25 mg vitamin B6, and 400 microg of vitamin B12) in patients with MTHFR gene defects found a reduction of homocysteine levels and improvement of migraines. [Pharmacogenetics and Genomics. 22(10):741-749, October 2012]
Paracetamol, ibuprofen, and nasal-spray sumatriptan are all effective symptomatic treatments for episodes of migraine (peds sys rv 2005). Migraleve is paracetamol, codeine (8mg), buclizine – for 10yr plus. Paramax, with metoclopramide, for 12 yr plus. Anti-emetic improves pain killer absorption so potential benefit even if no nausea!
Sumatriptan was previously contraindicated for hemiplegic migraine, but this was probably a theoretical concern, and there is evidence that it works. No caution or contraindication mentioned in BNF now.
Mefenamic acid for menstrual, esp with dysmenorrhea.
CGRP receptor antagonists – olcegepant, telcagepant [not in BNF]. Now erenumab [monthly subcut injections, BNF says specialist use only, minimum 4 migraines per month – SMC approved with restrictions], eptinezumab etc vs same calcitonin gene-related peptide receptor. Significant improvement in headaches in 40%, about 3 less headache days per month.
For prophylaxis, Pizotifen does not work (grade I evidence, plus makes you fat), flunarizine (CCB) is the most effective (not in BNF), also amitriptyline (dangerous in overdose), propanolol (dizziness, sleep disturbance, depression etc, also dangerous in overdose). Encouraging data (grade IV) for anti-epileptic mediations topiramate, valproate, levetiracetam, zonisamide. Cyproheptadine? Candesartan (anti-hypertensive, in BNF for migraine prevention)?
Always increase preventer dose to maximum before giving up, note that often symptoms worsen after initial benefit.
Current evidence on the efficacy of percutaneous closure of patent foramen ovale (PFO) for recurrent migraine is inadequate in quality and quantity. The evidence on safety shows a small incidence of well-recognised but sometimes serious adverse events, including device embolisation and device prolapse (each reported in less than 1% of patients). Therefore this procedure should only be used with special arrangements for clinical governance, consent and audit or research. [NICE]
Combined oral contraceptives are contraindicated in migraine with aura. But may be useful if menstrual pattern to headaches if no aura.
50% migraine in childhood remits at puberty. Onset in adolescence associated with persistence.
Patient support at Migraine Trust.
Poor sleep associated with hyperactivity, obesity, poor school performance, depression. And affects parents, of course! Caffeine and Propranolol (as used for migraine prophylaxis) affect sleep!
REM (rapid eye movement) phase is light sleep. Usually in later part of night after deep sleep. Slow wave (deep) sleep is associated with increased anabolic hormone release, mitotic repair. Higher proportion of sleep in adolescence is slow wave. 60% of newborn sleep is REM.
Recommended sleep duration: [National Sleep Foundation]
Some sources suggest adolescents have increased sleep requirements.
Late insomnia (early morning waking) in depression. Cf early – mood disorders, anxiety (cortisol vs melatonin).
30 mins high intensity exercise is as good as melatonin. But ideally 3hrs before bed time!?
Sleep latency 19 min under 2yrs, 17-19 mins thereafter.
Night wakenings are normal! But parental response varies!
Excessive sweating seen in 11% of children, so considered normal. But beware weight loss, lethargy! Can also be associated with obstructive sleep apnoea.
For infants not going to sleep, options are extinction vs gradual retreat. Not appropriate for under 6/12 of age as may affect bonding. No adverse effects otherwise.
Melatonin does not increase total sleep time! Helps prepare brain for sleep – does not induce sleep, as such. Earlier waking as well!
Nocturnal seizures – stereotyped, multiple in one night, sudden stop and start, mostly after first third of sleep. Seen in BECTS.
Restless legs associated with iron deficiency!
Benign nocturnal leg pain common in children.
Teenagers generally do have different body clock, but not helped by major changes in bed/wake times at the weekend. Blue light from screens suppresses natural melatonin production besides distraction.
For autism – Hope for autism do not need diagnosis, others do. Waiting times? National Autistic Society page. Arch, Reach websites.
CAMHS won’t prescribe melatonin but do prescribe methylphenidate!?
Bio melatonin 3x the price, not approved by SMC. Modified release melatonin may be useful with or without standard if early waking in night.
In early part of night, likely to be non REM, cf later in night.
Classic non REM =
REM related =
Sleep hygiene, then consider melatonin and CBT (stress often provokes non-REM). Benzodiazepines can help non REM but can worsen REM.
Beware Narcolepsy – poor sleep quality at night, then daytime somnolence, plus hypnagogic/hypnapompic hallucinations, sleep paralysis, cataplexy (laughing causes collapse). Genetic, treatable with stimulants.
1 in 5000 births. Mostly failure of Wolffian duct development, rarely failure of urethral canalisation.
2/3 detected antenatally, with distended bladder. If missed, then present with urinary tract infection, abnormal voiding (dribble rather than fountain!) else incontinence (if toilet trained, of course).
Later detrusor failure, tubular dysfunction, renal failure.
Hard to define – picky, restricted, faddy? Neophobia important – refusal to try new things. Only really a problem of the developed world… Refusal to eat unhealthy foods is obviously no bad thing…
Actually not much evidence about long term consequences – such studies are hard – poor fibre intake associated with constipation, persistent fussy eating may lead to being underweight, becoming a fussy adult or possibly an eating disorder. Avon longitudinal study (where most of the data comes from) found calorie intake maintained (some studies have found higher calorie intake in fussy eaters) but lower levels of iron, zinc, fibre and vitamin A. Intake of all but Vitamin A were below recommended levels for a substantial proportion of fussy children.
Peak age seems to be around 3yrs. Twin studies suggest highly heritable (due to heritability of sensitivity to bitterness) – associated with having fussy parents too. From an evolutionary perspective, non-mobile infants are only likely to be offered safe foods by their mother; once mobile however, risk of eating poisonous plants or contaminated foods. Hence probably why preference among fussy eaters is for bland flavours and colours, and non slimy textures.
Other risk factors are older mothers, higher maternal educational attainment, lower parity and lower birthweight. More precious children??
Avon longitudinal study found maternal worry about fussy eating at 15 months predicted fussy eating at age 3 (RR=3). Fresh fruit and eating the same meal as a family protective, ready meals increased risk of fussy eating.
Early introduction of vegetables before 6 months helps but goes against WHO guidance…
Australian study showed maternal healthy (adventurous) eating helps.
Parents get very emotional about the lack of variety in their child’s diet or perceived disinterest or refusal to eat. The often “internalise the child’s food intake as a reflection of their own parenting“, whereas choices of what and how much to eat are actually an expression of the child’s emerging autonomy.
Parental pressure to eat (usually fuelled by concerns the child is underweight, which is rarely the case) is associated with fussy eating, not surprisingly, but is potentially a vicious circle. Maternal negative affectivity, internalising problems, sensitivity (ie low tolerance) predicts fussy eating; authoritative parenting style protects [Norwegian studies]. The combination of modelling health eating (which means eating the same food together and not offering alternatives) and not pressuring definitely seems best.
[Caroline Taylor and Pauline Emmet, Bristol 2018]Current charts are UK-WHO, which is to say a combination of UK growth cohorts with world wide cohorts. This is to correct for the low prevalence of breast feeding and high prevalence of obesity in the UK, and assumes that there is little genetic differences in growth.
Downloads and online growth tool at RCPCH.
Between 37 and 42 get plotted as term. No centiles for first 2 weeks as dip expected. One in 5 still below birth weight at 2 weeks, only one in 50 will be 10% below or more. Still mainly well, but suggests feeding problem worthy of further assessment, and in a few there will be an otherwise occult pathological condition eg cardiac or metabolic disorder.
Preterms get plotted on both Preterm section of chart AND day 0! Because assessing early growth works best on day 0 centile, whereas later growth more likely to be related to preterm centile. Plot after birth on preterm section until you hit the end (42 weeks) then continue on to main 0-1yr chart, plotting a point for calendar age but adding arrow indicating gestational age. Otherwise unclear whether corrected or not.
Children up to age 2 get weighed without clothes or nappy. From 2, minimal clothing and no shoes. Height is hard! Only act on several measurements that appear consistent!
Infants are at high risk of undernutrition – high requirements for growth, frequent infections affecting appetite and increasing requirements, inefficient metabolism, dependence on adults for food!
See Growth charts for details on different centile charts available.
There are various ways of defining or looking for undernutrition:
“Failure to thrive” has gone out of fashion. “Thrive” seems to suggest something more than growth, but really we are just talking weight and height. “Failure” suggests not only that there is a definite problem, but also that it’s somebody’s fault! Variability in definition and use.
The main issue here is poor sensitivity and specificity for a genuine problem. 27% of Danish cohort infants met one or more of 7 different growth criteria in at least one of the two age groups (2–6 and 6–11 months of life). The concurrence among the criteria was generally poor, with most children identified by only one criterion. Positive predictive values of different criteria ranged from 1% to 58%. Most single criteria identified either less than half the cases of significant undernutrition (found in 3%) or included far too many, thus having a low positive predictive value. [Olsen, Arch Dis Child 2007;92:109-114 doi:10.1136/adc.2005.080333 ]
Things get even less consistent in older kids, where you can have low fat but apparently normal growth except at the extreme end of range.
Combination of weight faltering and low BMI is perhaps best. These kids subsequently have growth and body composition patterns suggestive of previous undernutrition. Overall, about 2/3 of kids with either weight faltering or low BMI probably adequate nutrition but variant growth pattern. Weight faltering kids are relatively short at follow up, but not more so than parents, so probably “catching down”. [Proceedings of the Nutrition Society. 71(4):545-55, 2012 Nov. PMID: 22954067]
Undernutrition is NOT associated with deprivation in UK, presumably as welfare focuses on families with young children. In the Gateshead Millennium Baby Study, both the highest and the lowest levels of deprivation were associated with weight faltering; this was independent of the type of milk feeding. No relation was found with maternal educational status.
Abuse and neglect are a factor in only a minority of cases.
Some evidence of differences in maternal feeding behaviour and appetite, eating behaviour. In Gateshead study maternal eating restraint (“I need to control how much I eat”) was unrelated to weight gain. Response to food refusal seems important.
In Gateshead study, infants of mothers with high depression symptom scores (EPDS >12) had significantly slower weight gain and increased rates of weight faltering up to 4 months (relative risk 2.5), especially if they came from deprived families, but by 12 months they were no different from the remainder of the cohort. [Arch Dis Child 2006;91:312-317 doi:10.1136/adc.2005.077750]
Either low appetite or actually not undernourished in strict sense!
Being faddy was only weakly associated with poor growth, and simply eating a limited variety was unrelated to growth [cf high eating restriction scores]. High milk consumption was associated with lower appetite but not with poor growth.[ Pediatrics. 120(4):e1069-75, 2007 Oct. UI: 17908727]
See Fussy eating
In Newcastle, There was a significant positive relationship between weight gain in infancy and picture vocabulary at age 10, adjusted for economic deprivation, gestational age and birthweight, but not with any of the other outcomes. There was a statistically significant association between birthweight and all four outcomes, where best outcome is at or just above average birthweight. In this population, the association between early growth and cognitive outcomes is stronger for growth before birth, postnatal weight gain having a relatively minor impact.[ Paediatr Perinat Epidemiol. 2007 Jan;21(1):57-64.]
Being able to see what happens in the house at mealtimes is the most useful thing! Interventions that include home visits work best. So Health Visitor is key.
Speech and Language, Dietician advice may be appropriate in some cases.
Identifying children with underlying medical problem important, even if these are a minority. Similarly those with social concerns. But proportionate response to symptoms and signs important, rather than long lists of investigations.
Although tempting, high energy oral supplements eg Pedisure suppress appetite for normal food. In series of 48 kids referred to a tertiary feeding clinic who were taking predominantly supplements (half neurodevelopmentally abnormal), most were successfully weaned off and had improved feeding behaviour a year later. Average weight Z score unchanged, 17% had significant catch up growth. [Archives of Disease in Childhood. 100(11):1024-7, 2015 Nov. UI: 25809349]
A neutrophil defect, prediposes to certain characteristic organisms. Frustrated neutrophils cause granulomas, hence the name: these are responsible for some other characteristic features of the disease.
Due to NADPH oxidase mutations, causing reduced oxidative burst (needed by neutrophils to kill pathogens after phagocytosis). Various types depending on which subunit affected. X linked gp91phox def (ie NADPH OXidase, due to CYBB gene defect) is severe, p47phox is autosomal and milder (NCF1 gene, partial activity retained). Other gene defects are CYBA and NCF2, funnily enough, and RAC2. Phenotype varies even between mono twins (factors?). Since non-oxidative killing is then the only remaining immune mechanism, the most important pathogens are catalase positive (an enzyme to make bugs resistant to the peroxide and superoxide produced by neutrophils or by the bacteria themselves as a toxic byproduct). Register exists in UK.
Usually present by 2 yrs but occ not until adulthood. Most commonly lymphadenitis (often culture negative), skin infections (esp perianal), pneumonia. Hepatomegaly is a clue. Other sites of infection are osteomyelitis, liver abscesses (distinctive, fibrous capsule, septated, thick contents – vague presentation, blood cultures usually negative so low index of suspicion).
Probably not the superoxides themselves that are important; MPO deficiency does not tend to present with infections! Critical step is probably degranulation of primary granules, with release of elastases etc. Superoxides probably deal with toxic metabolites rather than doing the killing.
Chronic inflammatory problems occur (due to having intact upregulated phagocytic activity with reduced apoptosis):
Mums who are carriers of CGD can be symptomatic even with fairly decent percentages of functional neutrophils incl aspergillus! Due to lyonization. Onset variable.
Nitroblue tetrazolium (NBT) test now replaced by Dihydrorhodamine test on flow cytometer (false positive esp in preterm so always check with reference lab). Only takes 15 mins!
The organisms found are also characteristic:
Note that you do NOT see PCP, strep, onychomycosis (despite susceptibility to fungus) or lymphomas (cf granulomas).
Patients are often anaemic with an iron-deficient pattern but resistant to iron supplementation (except in bowel disease, ?vitamin B12 def). ESR is often raised even when well. Less of a problem with CRP.
Co-trimoxazole prophylaxis (daily dosing, not 3x weekly as in PCP prophylaxis) good because active against typical bugs, and intracellular. Itraconazole is prophylactic vs Aspergillus.
Avoid BCG because of tendency to form abscess.
Cipro and Fluclox good for first line – effective against typical organisms, and cipro acts intracellularly. In serious pneumonia, empirical treatment should consist of Ceftazidime/Meropenem, Fluclox and Amphotericin. Because of the range of possible organisms, bacteriological diagnosis should not be delayed and tissue biopsy sought if non-invasive methods unsuccessful.
Steroids for colitis, cystitis and obstructive granulomatous disease. Also for poor wound healing!
Other adjuncts:
Median survival 30 years – NB compliance with prophylaxis by adolescents. So consider transplant.
[Clin Exp Imm 122(1); October 2000 pp 1-9 GOLDBLATT, D; THRASHER, AJ]
Potentially symptom of diabetes, chronic granulomatous disease, Hyper IgE syndrome – but more usually just an individual thing, or a nasty strain of staphlycoccus aureus.
GOS says if otherwise well (no other abscesses, no colitis, no weird organisms eg Serratia) then consider eradication with:
[http://www.gosh.nhs.uk/medical-information-0/search-medical-conditions/recurrent-boils]
Inborn errors of metabolism.
Cause ketotic hypoglycaemia (ie formation of ketones eg beta-hydroxybutyrate is intact), but accompanied by acidosis (unlike glycogen storage disorders) and usually encephalopathy and hyperammonaemia eg methylmalonic acidaemia.