11/14/2012 11:29:35 PM CHAPTER 13 Growth and puberty 484 Variants of normal puberty These include premature thelarche and premature adrenarche. Neit her condition is associated with pubertal activation of the hypothalamic \200\223pitu- itar y \200\223gonadal axis. Premature thelarche \200 Isolated premature breast development occurring in the absence of any other signs of pubert y. Typically, females present in infancy and usually by 2yrs of age. Breast development is due to the action of physiological or mild increases in the amounts of circulating estrogen . \200 The clinical course is characterized by a waxing and waning of breast size, normal growth ( height) rate, and the absence of any further sexual devel- opment. Breast development may b e asymmetrical, and there is usually a resolution of any breast enlargement by age 4 \200 \2235yrs. The cause is unknown, but small increases in basal and stimulated serum FSH levels are usua lly observed. In contrast LH levels remain suppressed in the prepubertal range. Ovarian fol licle development is often observed, but no changes in ovarian or uterine size are seen. Se rum oestradiol levels are increased when measured by sensitive assays, but typically within nor- mal range by standard radioimmunoassay. The condition is benign. Bone maturation, age of onset of menarche, and \201 nal adult he ight are not affected. Management is conservative with re-evaluation of growth and puberty stage at 3 \200\2236-monthly intervals. Thelarche variant \200 An intermediate condition between premature thelarche and central precocious puberty. It re presents a non-progressive form of early pubertal development. Patients have evidence of breast development, increased growth rate, and advanced skeletal maturation on bone age assessment. There may also be evidence of ovarian enlargement and ra ised serum oestradiol levels. For most patients the tempo of progression of pubertal develo pment will be slow and they will have laboratory \201 ndings within normal range for age. Management is usually conservative with regular re-evaluation of growth and pubertal statu s at 3 \200\2236 monthly intervals. Decisions to treat (as for central PP) are based on hei ght velocity and \201 nal height predictions. 13_McClure_13.indd 484 11/14/2012 11:29:36 PM VARIANTS OF NORMAL PUBERTY 485 Premature adrenarche Early onset of pubertal adrenal androgen secretion is a common variati on of normal pubertal development. Premature adenarche is the result of premature secretion of androgens from the zona reticualris of the adre- nal gland. \200 Children typically present with premature appearance of androgen- dependent s sexual hair d evelopment (axillary hair, pubic hair, or both), acne, and axillary (body) odor. Patients m ay have mild acceleration in height velocity and slight increase in BA. Laboratory investig ations reveal an increase in serum DHEAS levels that are appropriate for pubic hair stage r ather for than age. Serum concentrations of testosterone and 17-OH progesterone are normal. When evaluating patients for premature adrenarche it is important to assess for clinical si gns and symptoms that might indicate another cause of excess androgen production (e.g. adre nal tumor; congenital adrenal hyperplasia). The later are characterized with signs of viril ization, rapid growth rate, and signi \201 cantly advanced bone age. Premature adrenarche is a benign condition. The timing of onset of true puberty is normal a nd \201 nal adult height is unaffected. Management is conservative with reassurance after exclusion of other causes of adrenal androgen excess. Symptomatic treatment may be require d if adrenarche is pronounced, particularly in females who may go on to develop features of ovarian hyperandrogenism and the polycystic ovarian syndrome. 13_McClure_13.indd 485 11/14/2012 11:29:36 PM CHAPTER 13 Growth and puberty 486 Disorders of sex development Terminology \200 Sexual determination refers to the process that occurs from the time of conception until th e fetal bipotential gonad has been fully determined as either an ovary or testis. Sexual go nadal sex is determined until s sexual characteristics are fully expressed and fertility ac hieved. differentiation refers to the process that occurs from the time Disorders of sexual development The complex process of sexual determination and differentia tion may be interrupted. Numerous disorders that can result in genital ambiguity and uncert ainty about an infant \200\231s sex are recognized. Disorders of sexual dif- ferentiation m ay be classi \201 ed as genetic defects of gonadal determination (Box 13.4) or defects in androgen biosynthesis, metabolism, and action (excess or de \201 ciency). Box 13.4 Genetic disorders of gonadal determination \200 Gonadal dysgenesis: \200 \200 \200 \200 True hermaphroditism 46 XX or 46 XY sex rev ersal Camptomelic dysplasia (SOX-9 mutation) DAX-1 mutation Denys \200\223Drash syndrome (W T-1 mutation) 45 XO (gonadal dysgenesis) 46 XY (gonadal dysgenesis) 46 XX (gonadal dysgenesis) 45 XO/46 X Y (mixed gonadal dysgenesis) \200 \200 \200 \200 Virilization of 46 XX infants (female pseudohermaphrodite) \200 congenital adrenal hyperplasia \200\22421A- Excessive androgen production: hydroxylase de \201 ciency; 11B-hydroxylase de \201 ciency ; 3BHSD Defect in androgen exposure: Maternal steroid exposure \200 placental \200\223fetal aromatase de \201 ciency Under-virilization of 46 XY male (male pseudohermaphrodite) \200 Defect in testosterone production: \200 Leydig cell hypoplasia/agenesis defects of testic ular and adrenal steroidogenesis \200 17A-hydroxylase/17,20 lyase de \201 ciency \200\224StAR; 3BHSD; \200 5A-reductase de \201 ciency androgen insensitivity syndrome: Defect in testosterone metabolism: Defects in testosterone action: complete or partial 13_McClure_13.indd 486 11/14/2012 11:29:36 PM DISORDERS OF SEX DEVELOPMENT 487 Assessment History A detailed history should be obtained and should include: \200 Family history: inguinal hernia. Prenatal history: maternal virilization during pregnancy. History of previous stillbirths or neonatal death? ambiguous genitalia; disorders/problems of puberty; maternal health; drugs taken during pregnancy; Examination \200 dysmorphic features or midline defects; state of General examination: hydration; BP. Are the gonads palpable? ovotestes. Assess the degree o f virilization: \200 Prader stage (Fig 13.2). \200 External masculinization score. Meas ure the length of the phallus: \200 If \200\230yes \200\231 they are likely to be testes or Normal term penis is about 3cm (stretched length from pubic tubercle to tip of penis). Micr openis is a length <2.0 \200\2232.5cm. Penis: Vagina: Appearance of labioscrotal folds. Position of urethral opening. Skin \200 \224pigmentation of genital skin: adrenocorticotrophin (ACTH) and opiomelanocortin in CAH. \200 \200 \200 \200 presence of chordee. locate opening? hyperpigmentation with excessive In preterm girls clitoris and labia minora are relatively prominent. In pre- term boys, tes tes remain undescended until 34wks gestation. Fig. 13.2 Prader staging: virilization. Reproduced from Prader A. (1058). Die Hau \201 gke it der kongenitalen adrenigenitalen syndrome. Helv Paediatr Acta 13: 5 \200\22314 and 426 \200\22331. With kind permission of Springer Science and Business Media. 13_McClure_13.indd 487 11/14/2012 11:29:36 PM CHAPTER 13 Growth and puberty 488 Disorders of sex development: management Investigations Laboratory \200 Genetic sex determination: (takes 3 \200\2235 days). Serum electrolytes. Blood sugar (hypog lycaemia). Adrenal androgens: steroid pro \201 le; LH and FSH. Molecular genetic studies; blood (DNA). FISH for Y and X chromosomes; karyotype \200 \200 plasma testosterone; 17-OH progesterone; urine If a male/mosaic karyotype is con \201 rmed, further investigations are directed at establ ishing whether testicular tissue is capable of producing androgens: \200 \200 \200 \200 hCG stimulation test; testosterone: DHT ratio; androgen receptor binding studies; genital s kin biopsy ( \201 broblast). Imaging studies \200 US scan pelvis: \200 US scan abdomen: \200 Urogenital sonogram. \200 MRI. anatomy of urogenital sinus/vagina/uterus. renal anomalies. Internal examination \200 \200 \200 Examination under anesthesia (+/ \200\223 cystography). Laparoscopy. Gonadal biopsy. Management This is professionally challenging and requires a multidisciplinary team includi ng the following: \200 \200 \200 \200 \200 \200 \200 \200 Pediatric endocrinologist. Neonatologist. Pediatric urologist. Gynecologist. Geneticist. Ra diologist. Psychologist. Clinical biochemist. 13_McClure_13.indd 488 11/14/2012 11:29:36 PM DISORDERS OF SEX DEVELOPMENT: MANAGEMENT 489 Most infants presenting with a disorder of sexual differentiation will pre- sent with ambig uous genitalia at birth. \200 Parents and their relatives will be anxious to know the sex of their newborn baby. Decision s about an infant \200\231s sex (sex assignment) must be delayed until the multidisciplinar y team has carried out a thorough assessment. Birth registration must be delayed until this has been completed and an agreement on sex assignment has been made with the parents (see Box 13.5). Box 13.5 General principles of sex assignment Virilized females \200 \200 \200 Should be brought up as female Clitoromegaly: Vaginoplasty is deferred until late childhood /early adolescence clitoral reduction (clitoroplasty) in infancy/childhood Under-virilized male Decision regarding sex assignment is more complex. Depends on the foll owing: \200 \200 \200 \200 Degree of sexual ambiguity Underlying cause if known Potential for normal sexual function a nd fertility Phallic size: \200 \200 if >2.5cm, reconstructive surgery more likely to be successful a trial of IM testosterone o r topical dihydrotestosterone cream may improve phallic size Gonadectomy is required: \200 \200 \200 If dysgenetic testis If complete androgen insensitivity syndrome (AIS) If decision to raise as female Hormone replacement therapy \200 \200 Testosterone therapy if decision to raise as male Estrogen therapy if decision to raise as female Psychological support \200 \200 Experienced counseling is essential Patient support groups are available Issues regarding assignment of gender, timing of reconstructive surgery, and hormone replac ement therapy are complex. Current consensus on management is largely based on expert opini on.1 Reference 1 Hughes IA, Houk C, Ahmed SF, et al. (2006). Consensus statement on the manageme nt of inter- sex disorders. Arch Dis Child 91(7): 554 \200\22363. 13_McClure_13.indd 489 11/14/2012 11:29:36 PM CHAPTER 13 Growth and puberty 490 Androgen insensitivity syndrome This condition is due to defects in the androgen receptor a nd results in a spectrum of under-virilized phenotypes in the 46XY patient. Complete AIS Deletions of the gene and certain mutations can result in a completely female phenotype. \200 External genitalia are unambiguously female, with normal clitoris, hypoplastic labia majora , and blind-ending vaginal pouch. M llerian structures are absent. Testes may be located i n the abdomen, inguinal canal, or labia. AIS should be strongly suspected and excluded in a ny female presenting with inguinal hernia. Patients with complete AIS often present in adol escence with primary amenorrhoea. At puberty, serum levels of testosterone and LH are eleva ted. Conversion of testosterone to oestradiol in the testis and in peripheral tissues resul ts in normal breast development. Pubic and axillary hair development is absent or sparse. D iagnosis is con \201 rmed by demonstrating 46XY karyotype. \200 \200 In view of the potential risk of malignant transformation if retained, removal of the testi s either soon after diagnosis or after the completion of puberty is carried out. After gona dal removal, estrogen replacement therapy is given. Partial AIS Certain mutations of the androgen receptor gene result in a partial form of AIS . There is a wide spectrum of phenotypic expression ranging from ambiguous genitalia to a n ormal male phenotype presenting with fertility dif \201 culties. There is, however, poor g enotype \200\223phenotype correlation and patients with the same mutation present with diff erent phenotypes. Management is much more challenging. Sex assignment depends on the degree of genital ambiguity. True hermaphroditism Individuals have both ovarian tissue with follicles and testicular tis sue with seminiferous tubules either in the same gonad (ovotestis) or with an ova- ry on on e side and a testis on the other. The etiology of this condi- tion is unclear. In 70% of ca ses the underlying karyotype is 46XX; 20% 46XX/46XY; 10% 46XY. Ovotestes may be present bilaterally and may be located in the inguinal canal. The external genitalia are most often ambiguous, although in 10% phenotype may be female. The degree of feminization and virilization that occurs varies widely. Management is dictated by sex ass ignment. Dysgenetic testicular tissue should be removed because of the risk of malignant tr ansformation. 13_McClure_13.indd 490 11/14/2012 11:29:36 PM MICROPENIS 491 Micropenis Micropenis is often an incidental \201 nding on newborn examination. An intact hypothalamic \200\223pituitary \200\223gonadal axis is required for the forma- ti on of a normal-sized phallus and for descent of the testis. Both GH and the gonadotrophins are required for phallic growth. The \201 nding of micropenis warrants assessment of hypothalamic \200\223pitu- itary func tion and exclusion of both GH de \201 ciency and HH. Micropenis may also be part of a synd rome causing ambiguous genitalia. Evaluation Penile size \200 \200 \200 Measured from pubic tubercle to tip of stretched penis in a term baby. Normal size at birth is usually >3cm. Micropenis <2.2 \200\2232.5cm (varies with ethnicity). General examination \200 Dysmorphism. \200 Midline craniofacial defects. Ophthalmic examination Optic nerve hypoplasia/septo-optic dysplasia. Investigations \200 \200 \200 US of head for midline defects. MRI head. Anterior pituitary hormone levels (basal and stim ulated): cortisol; GH (IGF-I, IGFBP3); LH and FSH; TSH and fT4. Karyotype. ACTH and Management Referral to a pediatric urologist is often required. If severe micropenis is pre sent a decision regarding sex assignment will be needed. Treatment with a short course of IM testosterone or topical application of dihydrotestoster one cream may stimulate penile growth and improve appearances. 13_McClure_13.indd 491 11/14/2012 11:29:36 PM CHAPTER 13 Growth and puberty 492 Gynaecomastia This is a condition affecting boys in which there is hyperplasia of the glan- dular tissue of the breast resulting in enlargement of one or both breasts. It is a common condition with 3 well-de \201 ned time periods of occurrence: \200 \200 \200 neonatal; puberty; during older adult life. It is due to either an imbalance in the normal systemic or local estrogen/ androgen ratio. An absolute or relative increase in estrogen levels, local breast tissue hypersentivity to oestrogens, or a decrease in the produc- tion, or action of free androgen levels may induce gynaecomastia. Etiology A number of diverse causes are recognized (Box 13.6). Gynaecomastia must be differ entiated from pseudogynaecomastia, which is breast enlargement due to fat accumulation. Box 13.6 Classi \201 cation and causes of gynaecomastia \200 \200 \200 Pubertal gynaecomastia Neonatal gynaecomastia Impaired gonadal function: \200 \200 Andr ogen insensitivity syndrome Adrenal tumors Testicular tumors: \200 \200 \200 Iatrogen ic: \200 \200 \200 Alcohol excess Cannabis hypogonadotrophic hypogonadism hypergonadotrophic hypogonadism \200 \200 Leydig cell tumor Sertoli cell tumor germ cell tumor exogenous hormones, e.g. estrogen, anabolic steroids ketoconazole psychoactive drugs, e.g. diazepam, phenothiazines \200 13_McClure_13.indd 492 11/14/2012 11:29:36 PM GYNAECOMASTIA 493 Pubertal gynaecomastia This is most common cause of gynaecomastia in children and adolescen ts. The exact cause remains unclear. Proposed mechanisms include altera- tions in the rate of change in estrogen and androgen production during puberty and/or hypersensitivity of bre ast tissue to estrogen. May affect 40 \200\22350% of children to some degree. It also depends on eth- nicity and nu tritional status. Usual age of onset of development is just before puberty (ages 10 \200 \22312yrs), peaking during puberty (age 13 \200\22314yrs). In the majority of children the gynaecomastia usually involutes after 1 \200\2232yrs and is generally resolved by end of pu berty (age 16 \200\22317yrs). The diagnosis is established by excluding other possible causes of gynae- comastia by takin g a detailed clinical and family history, and examination. Investigations should include: \200 \200 \200 \200 serum estrogen, testosterone, LH, FSH; serum prolactin; LFT; thyroid function tests; karyot ype. Where testicular/adrenal/hepatic tumor is suspected the following inves- tigations should b e considered: \200 \200 \200 US abdomen/testis; MRI abdomen/testis; BhCG levels. serum Management Reassurance and explanation are usually suf \201 cient for pubertal gynaeco- ma stia. In severe cases where pubertal gynaecomastia is causing signi \201 cant pyschologica l distress or where gynaecomastia persists beyond puberty, surgical resection of excess gla ndular breast tissue is warranted. The role of medical therapy with aromatase inhibitors or with selective estrogen receptor blocking agents (e.g. tamoxifen) is currently unclear. 13_McClure_13.indd 493 11/14/2012 11:29:36 PM This page intentionally left blank 495 Chapter 14 Neurology Examination 496 Examination: children aged <5 years who can \200\231t walk 498 Congenital a bnormalities 500 Paroxysmal episodes: not epilepsy 502 Paroxysmal episodes: general managem ent 504 Seizures and childhood epilepsies 505 Seizures: management 506 Epilepsies: neonatal 508 Epilepsies: infantile 510 Epilepsies: mid to late childhood (1) 512 Epilepsies: mid to late childhood (2) 514 Headache 516 Headache: migraine 518 Bell \200\231s palsy 519 Acute disseminated encephalomyelitis 520 Stroke in childhood 522 Acute abnormal movements 524 Sub dural hemorrhage in a child under 2 years 526 Neurocutaneous disorders 530 Macrocephaly and microcephaly 534 Degenerative disorders 536 Neuromuscular disorders 538 Peripheral neuropa thies 541 Guillain \200\223Barr syndrome 542 Neuromuscular junction 544 Muscular disorder s 546 Management of neuromuscular junction and muscular disorders 548 Cerebral palsy 550 Acute encephalopathy 552 14_McClure_14.indd 495 11/14/2012 3:36:05 PM CHAPTER 14 Neurology 496 Examination This is the most useful tool in assessing children with neurological disor- der s. Nevertheless, it is neglected and often thought dif \201 cult. With a few simple tricks it is both easy and enjoyable for doctor, child and parent. Children with mental age >4 years who can walk Older children can undergo the full \200 \230adult \200\231 neurological examination by making it a game. Pay particular attention t o their: \200 \200 \200 \200 affect; gait and spine; head size; skin: neurocutaneous stigmata. Children able to walk with a mental age <5 years Such children can be examined by stealth, then moving onto a game. Observe the play and note: \200 Gait, watch how they walk, narrow/normal/wide based, heel/toe strike, walk in a straight li ne \200\230on a tight rope \200\231, turn quickly around (cerebellar function); symmetric or asymmetric, do they perform the Gower \200\231s maneuver (assessing proximal muscle stre ngth). Visual acuity, hearing, speech. Behavior, Movements. \200 \200 Examine: \200 \200 Skin, spine, and head circumference. Co-ordination (taxis) and formation of movement (praxi s) by simple games. \200\230Take this bread from my hand \200\231, \200\230Pretend to ope n a door \200\231. Cranial nerves (II, III, IV, VI) \200 \200 Look at the child \200\231s eyes. Do they \201 x and follow? Move an interesting toy and watch child \200\231s eye movements. Get the child to look at you. Will they look left or r ight when the toy comes in from each side of their visual \201 eld? Is there a squint, is it the common type \200\224non-paralytic \200\224where they can move the eyes fully, but w ith asymmetry? Get a carer to stand behind you and wiggle their nose. Ask the child to \200\230see if you can count how many times daddy wiggles his nose \200\231, then look at t heir fundi by asking them to look at daddies nose and ask him to keep the child gaze on her . Other cranial nerves \200 \200 Watch the facial movements (VII). Say something with your hand covering your mouth and see if the child responds appropriately (VIII). Does the child dribble excessively? Ask a carer or watch them swallow and listen to their articulation of speech (IX, X). Children love to stick out their tongues and shrug their shoulders (XI, XII). 14_McClure_14.indd 496 11/14/2012 3:36:05 PM EXAMINATION 497 Neuromuscular and peripheral examination Children who can walk, run, jump, hop, and spring up form the ground well are very unlikely to have an abnormality of the peripheral neurolog i- cal system that will be identi \201 ed on further examination. However, if there is an abnormality do the following. \200 \200 Remove clothes as far as underwear if the child is happy. Look at the gait. Where does the foot strike? Heel or toe? Is it waddling, asymmetrical, is there abnormality of posture? Ob serve the muscle bulk and joint positions with particular reference to scoliosis, lordosis, hip \202 exion, ankle inversion, or eversion. Assess the upper limbs for joint ranges, t one, and power, by having a game with the child. Laugh and keep praising them. Use an adult tendon hammer and elicit the re \202 exes, but place your thumb over the biceps and brach ioradialis. Have another game as you assess the same in the lower limbs. Try to categorize the pattern into increased or decreased tone. Is it mainly unilateral; or bilateral, but ma inly in the legs, or in all four limbs, and possibly the bulbar muscles? \200 Sensation If indicated assess sensation by asking them to close their eyes and say \200 \230Luton \200\231 every time they feel your touch. Note that children do not like closing their eyes with a stranger, so reassure them by doing it \201 rst on daddy, then with eye s open (brie \202 y), \201 nally with their eyes closed. Move around dermatome by dermat ome, but move irregularly when you will touch them, otherwise they may say they can feel it by guessing when the next touch is likely to come. 14_McClure_14.indd 497 11/14/2012 3:36:05 PM CHAPTER 14 Neurology 498 Examination: children aged <5 years who can \200\231t walk Observe and note the following: \200 \200 \200 Developmental stage. Can they see, hear, or move? Do they vocalize? Are they dysmorphic? Ar e their orthoses, e.g. wheelchair, visible? Examination Don \200\231t rush to get the child \200\231s clothes off as you will frighten them. Examine the following: \200 \200 \200 \200 Skin for neurocutaneous stigmata; Spine; Fundi; Head circumference (when they like you, or at the end of the examination if you haven \200\231t managed to break the ice). Check for d ysmorphic features. Cranial nerves (II, III, IV, VI) \200 Check visual acuity. Will they \201 x on a small toy or large object, e.g. toy, face, bri ght light? If they do not \201 x are they pupil responses, i.e. is the child blind? Will they follow it? Are their eyes symmetrical with a full range of movement, when following sm all and large toys? Other cranial nerves. Will they respond to a quiet, moderate, or loud s ound (VIII)? Elicit a smile, or wait to see if there is a grimace (VII). Ask about or watch their swallow (IX, X). \200 \200 \200 Neuromuscular and peripheral examination \200 Observe their best motor function: lifting head up; sitting up; or pulling to stand. Place your little \201 ngers in their hands while lying supine. Do they have a primitive grasp re \202 ex? Then pull them up off their bed, watching for head lag, which would imply low tone, reduced power, or both. If child has head control, see if they can sit with or withou t support. Pick them up under their armpits. Do they slip through your hands (a sign of hyp otonia)? Then assess their parachute and moro re \202 exes (see Power: Tone: Re \202 exes your thumb over the tendons. Co-ordination: if age-appropriate, assess \201 ne motor abi lity by presenting an attractive target for them to take or grasp with either a primitive o r pincer grasp. Sensation is dif \201 cult to access in children with mental age <2. A clu e to an abnormality may be inferred from other signs (e.g. skin, peripheral motor system). antigravity movement; rolling over; \200 \200 \200 \200 b pp.145, 558). observe the movements and pattern of any paucity. gently manipulate joints, but take care t o avoid trauma. : use an adult tendon hammer and elicit the re \202 exes, but place 14_McClure_14.indd 498 11/14/2012 3:36:05 PM EXAMINATION: CHILDREN AGED <5 YEARS WHO CAN \200\231T WALK 499 14_McClure_14.indd 499 11/14/2012 3:36:05 PM CHAPTER 14 Neurology 500 Congenital abnormalities There are many disorders that can affect the brain. The majority a re classed as disorders of neuronal migration or cortical dysplasia and are thought to eith er be genetically programmed, due to gene mutation, or a disruption of fetal development du e to a deleterious process between the 6th and 16th week of pregnancy, e.g. vascular or vir al. They are nor- mally associated with developmental delay, may have a cerebral palsy, and can have very troublesome epilepsies. Investigation This is normally initiated after an abnormality is licked up on standard MRI scan of the head. Unless the disorder is likely to have been caused by a single process, e. g. mutation in the Lis1 gene causing the majority of children with isolated lissencephaly, then it is important to perform a full examination and look for other stigmata of a genetic or acquired disorder. For example, dysmorphic features, for the former, and stigmata of in fec- tion for the latter. Most children will bene \201 t from exact radiological classi \201 cation of the abnormal ity, and associated changes on examination/history, then tar- geted genetic investigation. If this fails, then karyotype and micro array analyzes should be undertaken. Lissencephaly \200\230smooth brain \200\231 There is absence of normal gyri on the cerebra l cortex (Fig. 14.1). The children may have unusual facial appearance, dif \201 culty swal lowing, failure to thrive, seizures, and severe learning disability. Hands, \201 ngers, o r toes may be deformed. It may be associated with other diseases including, Miller-Dieker a nd Walker-Warburg syndromes. Where multiple genes are deleted, e.g. Miller-Dieker, then wid er malformations are seen. In isolated lissencephaly, the majority will either have a chang e within the Lis1 gene, or it is completely lost (Miller-Dieker). Fig. 14.1 T2-weighted axial MRI images of a lissencephalic brain. 14_McClure_14.indd 500 11/14/2012 3:36:05 PM CONGENITAL ABNORMALITIES 501 Pachygyria Here, there is a paucity of gyri vs the absence in lissencephaly. Although milde r, it is associated with a very similar range of complications and man- agement is similar. Heterotopia In these disorders there is abnormal positioning of the white/gray matter (Fig. 14.2). It is more commonly used to describe abnormal migration of gray matter. It can be a single area, multiple, nodular or a band. Milder than either of the above, many children w ill be normal, or present later in life with events such as new onset seizures. Fig. 14.2 T2-weighted axial MRI scan, showing a isolated area of heterotopia in the right h emisphere. Cortical dysplasias These can occur as either a very small or large lesion. Either can be a ssoci- ated with learning dif \201 culties, and especially seizures. One in particular is very well recognized \200\224perisylvian polymicrogyria \200\224which is associated with ve ry troublesome seizures and bulbar dif \201 culties. There is a particular type of cerebra l palsy which primarily affects the bulbar muscles (unlike diple- gias, hemiplegias and qua dripleagias, where bulbar signs are normally much milder than those in the limbs. It is kno wn as Worster-Drought syndrome. Agenesis of the corpus callosum Can occur as an isolated \201 nding, or in more widesprea d disorders, e.g. Aicardi Syndrome. It is isolated, children may be almost normal, but as i n other disorders there is a signi \201 cant chance of learning dif \201 culties, and esp ecially seizures. 14_McClure_14.indd 501 11/14/2012 3:36:06 PM CHAPTER 14 Neurology 502 Paroxysmal episodes: not epilepsy Up to one-third of children diagnosed with \200\230epile psy \200\231 actually have non- epileptic events. In adolescents presenting to emergency te ams in \200\230sta- tus epilepticus \200\231, over half turn out to have non-epileptic psy chologically induced episodes. Think carefully about other paroxysmal episodes (such as tho se described below) before diagnosing a form of epilepsy and treat- ing the child with anti convulsants. Etiology It is best to consider the cause of paroxysmal episodes according to the age of th e child. Neonates and infants \200 Benign neonatal sleep myoclonus: of jerking of arms and legs (typically while falling aslee p after a feed) and sparing the face. Shuddering attacks. these are single or repetitive episodes Older infants and toddlers \200 history of suddenly going limp (or \200\230Breath-holding attacks \200\231 and RAS: syncop e), which may be followed by clonic jerking (e.g. RAS). On closer questioning at least 1 ep isode has been triggered by a noxious stimulus (e.g. banging head). Typically, there is a s hort cry and then the child goes limp, collapses to \202 oor, and may have brief jerking movements. Other episodes are characterized by \200\230blue \200\231 breath-holding where the child starts to cry for any reason, the crying builds up, and then the child collapses to the \202 oor at the end of expiration. Masturbation and other grati \201 cation pheno mena: is bored they indulge in self-stimulation. In girls, the legs are held outstretched, and the eyes are glazed. Sweatiness almost invariably raises the possibility of a tonic sei zure and these episodes are commonly mistreated as epilepsy. Febrile myoclonus: Benign paro xysmal vertigo of childhood: vertigo, and unsteadiness if forced to walk. Rarely, the child vomits and they may have nystagmus. Benign paroxysmal torticollis: nystagmus seen in benig n paroxysmal vertigo. Night terrors: suddenly wakes up and is inconsolable. This lasts some 10 \200\22320min and then child \200\230wakes \200\231, looks confused, rolls over, and s leeps again. when the child \200 short jerks associated with high fever. acute onset of fear, nausea, acute episodes of head tilt, similar to the while in deep sleep, about 1 \200\2232hr after bed, the child Childhood Daydreaming This episode can appear very similar to an absence seizure. However, the latter will occur at home during activity as well as at school. Classical absences, as part of an idiopathic generalized epilepsy (see b p.512), can be elicited on an EEG (taken during normal and sleep deprived state) in over 95% of cases. They are short, associated wi th abrupt psychomo- tor arrest and immediate resumption of activity, speech, and thought. 14_McClure_14.indd 502 11/14/2012 3:36:06 PM PAROXYSMAL EPISODES: NOT EPILEPSY 503 Absences as part of a focal seizure disorder will only very rarely occur without some other suggestive feature such as an automatism, abnormal movement, or postictal state. Syncope \200 \200 Also known as fainting. Occurs from age 7mths onwards. There may well be a history of preci pitating events (e.g. fright, head bang, sudden standing, hair- brushing). Often the child has an aura of loss of vision, tingling, and auditory phenomen, this is followed by loss of consciousness and posture change: falls over if standing. Not all syncopal events result i n a loss of tone. In some, the fall is accompanied by increased tone. Myoclonic jerks may f ollow for a few seconds. Useful tools in diagnosis include: a history of a precipitant; jer king lasting less than 20secs; and the movements may not be rhythmic. If in doubt assume th at it is syncope until there is evidence otherwise (see Psychologically determined paroxysm al events (PDPE)). (cid:1) Caution If there is a history of sudden death in the family, or of syn- cope induce d by sudden physical stress such as exercise or sleep, long QT syndrome should be investiga ted. Psychologically determined paroxysmal events (PDPE) This is a less pejorative term to descr ibe episodes of psychological origin that used to be described as hysteria, and more recent ly as pseudosei- zures, malingering, factitious or conversion disorders. The episodes are a psychological phenomenon, although identifying or looking for the psy- chological causes a t time of diagnosis can be misleading or even counter- productive. There is no single event that will separate them from epilepsy. Some children rarely may even have both. Features suggestive of, but not diagnostic of PDPE \200 \200 Events triggered by speci \201 c situations Events with convulsive movements that are not explained anatomically, e.g. left arm jerking, then lull followed by right leg Thrashing mo vements that wax and wane, +/ \200\223 pelvic thrusting Eyes open during the episode Slumpi ng to the \202 oor in a dramatic manner. Falls without injury Violence, rather than viole nt movements Gain from the situation Generalized movements with rapid return to normal \200 \200 \200 \200 \200 These features are not diagnostic. There is no never or always. In partic- ular, young peop le can injure themselves and pass urine in PDPE, which are often misreported as a diagnosti c feature of genuine seizures (see b p.505). 14_McClure_14.indd 503 11/14/2012 3:36:06 PM CHAPTER 14 Neurology 504 Paroxysmal episodes: general management Assessment History The majority of paroxysmal episodes can be classi \201 ed with a careful his- tory . No episode can be safely classi \201 ed, even after EEG and MRI, if an adequate history has not been taken. Take details of the following: \200 when, where, what happened, and the child \200\231s First episode: responsiveness; how long , recovery, and talk to the witness. Subsequent episodes: Full medical history, family hist ory, developmental and psychosocial history. \200 situation, precipitants, duration, frequency. Video If you are unsure about the diagnosis, then request the carers to take a vid- eo reco rding of the event. Do not investigate or treat until the diagnosis is con \201 rmed. Chil dren are safer off treatment, when the clinician is unsure, if the caution below is followe d. Even when you are sure of the diagnosis, it is good clinical practice to request video r ecording of all different parox- ysmal events, since the episodes or events may evolve. (cid:1) Caution Even when the diagnosis could be a non-epileptic disorder, until this is co n \201 rmed, the carers should be advised how to manage a genuine seizure. The child shoul d avoid speci \201 c dangers: - - - - injury from fall proximity to swimming water without an identi \201 ed lifeguard unprotect ed heat moving objects and machinery Management Infantile non-epileptic disorders, syncopal episodes and jerks Allay the carers \200\231 concerns over the diagnosis. Psychologically determined paroxysmal events See b p.503. PDPE can be dif \201 cult to tre at, but these patients do respond to well organized management. The principal areas include the following: \200 Unambivalent diagnosis explained to both the parent and the child/ y oung person. Acknowledgement/acceptance by the young person, carers and all health professi onals that these are non-epileptic. Stabilization phase where the family is developing unde rstanding. Strengthen coping abilities and remove gain from the behavior. Psychological sup port is essential. Some families will feel very threatened when the possibility is raised o f looking at psychological issues that may have triggered these events in the child. \200 \200 14_McClure_14.indd 504 11/14/2012 3:36:06 PM SEIZURES AND CHILDHOOD EPILEPSIES 505 Seizures and childhood epilepsies One per cent of children will have had one seizure, not a ssociated with fever, by the age of 14yrs. The majority of these seizures will be general- ized tonic \200\223clonic episodes. Forms of epilepsy The two main forms of epilepsies can be categorized as having generalized or focal seizures. Generalized seizures These can be described as follows: \200 with shock-like movement of one/several parts or the whole Myoclonic: body. Tonic: with sustained contraction and stiffness. with rhythmic jerking of one limb, one side, or all of the Clonic: body. (See how this contrasts with the descriptio n of psychologically determined clinical events, b p.503). Tonic \200\223clonic: Absence: 5 \200\22315s in younger children, but can be longer in the older child. They can be associa ted with retropulsion of the head, upward deviation of eyes and eyelid, or perioral myoclon ia. (You should note that facial myoclonia can be asymmetrical and give the impression of a \200\230focal \200\231 seizure). \200 \200 a combination of the above forms. these are episodes of abrupt psychomotor arrest lasting Focal seizures These seizures start in one area of the brain and then may spread, and ultim ately generalize. If the latter part of the event is witnessed it may be described incorrec tly as being primarily generalized. The semiology depends on the locality of the initial el ectrical activity. \200\230Typical \200\231 seizure semiology includes the following: \200 Occipital: homonymous visual \201 elds. Centroparietal: marching up one side of the body. Temporal: disturbances (e.g. familiarity, \200\230d j vu \200\231), autonomia (e.g. au tomatisms such as nose rubbing), and contralateral clonic or dystonic movements. Frontal: multicolored bright lights spreading from one area of sensorimotor phenomena spreading from one limb and feelings of gastric discomfort, strangeness, anxiety, memory dystonic posturing and strange guttural noises. Status epilepticus (StE) StE can be convulsive with tonic/clonic movements. Alternatively, it can be non-convulsive with impairment of consciousness and often subtle twitch- ing. Tec hnically, StE is a seizure lasting for more than 30min, or repeated seizures lasting more t han 30min without recovery of consciousness in between. Practically, though, the treatment algorithm for StE can be used once a convulsive seizure has lasted longer than 5min (see b pp.80 \200\22381). 14_McClure_14.indd 505 11/14/2012 3:36:06 PM CHAPTER 14 Neurology 506 Seizures: management First unprovoked seizure \200 