Morning Rounds \u00b7 Neonatal Seizures<\/title>\n<link href=\"https:\/\/fonts.googleapis.com\/css2?family=Playfair+Display:ital,wght@0,400;0,600;0,700;1,400;1,600&family=Source+Serif+4:ital,wght@0,300;0,400;0,600;1,400&display=swap\" rel=\"stylesheet\">\n<style>\n#neo05 *,#neo05 *::before,#neo05 *::after{box-sizing:border-box;margin:0;padding:0}\n#neo05{\n --ter:#8B3A3A;\n --ter-light:#A85050;\n --ter-pale:#F9EDED;\n --ter-dark:#5C1E1E;\n --correct:#2D6B47;--correct-bg:#EAF6EF;--correct-border:#3A9960;\n --wrong:#B83232;--wrong-bg:#FDF0F0;--wrong-border:#E53935;\n --ink:#2A1010;--ink-mid:#5A3030;--ink-soft:#9A7070;\n --line:#EDD8D8;--cream:#FDF4F4;--warm:#FFFAFA;\n font-family:'Source Serif 4',Georgia,serif;\n font-size:16px;color:var(--ink);background:var(--cream);\n line-height:1.7;padding:0 0 64px;\n}\n#neo05 .mr-header{background:var(--ter);color:#FFFAFA;padding:34px 24px 28px;text-align:center}\n#neo05 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style=\"width:100%;max-width:620px;display:block;margin:0 auto\" aria-label=\"Causes of neonatal seizures by time of onset\">\n <rect width=\"620\" height=\"168\" rx=\"6\" fill=\"#FFFAFA\"\/>\n \n <rect x=\"8\" y=\"8\" width=\"140\" height=\"28\" rx=\"4\" fill=\"#E8C0C0\"\/>\n <rect x=\"158\" y=\"8\" width=\"138\" height=\"28\" rx=\"4\" fill=\"#C97A7A\"\/>\n <rect x=\"306\" y=\"8\" width=\"138\" height=\"28\" rx=\"4\" fill=\"#8B3A3A\"\/>\n <rect x=\"454\" y=\"8\" width=\"158\" height=\"28\" rx=\"4\" fill=\"#5C1E1E\"\/>\n <text x=\"78\" y=\"27\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" font-weight=\"700\" fill=\"#5C1E1E\">Onset<\/text>\n <text x=\"227\" y=\"27\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" font-weight=\"700\" fill=\"#FFFAFA\">0 – 24 h<\/text>\n <text x=\"375\" y=\"27\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" font-weight=\"700\" fill=\"#FFFAFA\">24 – 72 h<\/text>\n <text x=\"533\" y=\"27\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" font-weight=\"700\" fill=\"#FFFAFA\">72 h – 1 week<\/text>\n \n <rect x=\"0\" y=\"44\" width=\"620\" height=\"30\" fill=\"#FDF4F4\"\/>\n <rect x=\"0\" y=\"74\" width=\"620\" height=\"30\" fill=\"#FFFAFA\"\/>\n <rect x=\"0\" y=\"104\" width=\"620\" height=\"30\" fill=\"#FDF4F4\"\/>\n <rect x=\"0\" y=\"134\" width=\"620\" height=\"30\" fill=\"#FFFAFA\"\/>\n \n <text x=\"6\" y=\"65\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"9\" font-weight=\"700\" fill=\"#9A7070\">Common<\/text>\n <text x=\"6\" y=\"95\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"9\" font-weight=\"700\" fill=\"#9A7070\">Metabolic<\/text>\n <text x=\"6\" y=\"125\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"9\" font-weight=\"700\" fill=\"#9A7070\">Infective<\/text>\n <text x=\"6\" y=\"155\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"9\" font-weight=\"700\" fill=\"#9A7070\">Other<\/text>\n \n <text x=\"227\" y=\"59\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">HIE (commonest)<\/text>\n <text x=\"227\" y=\"71\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">intracranial haemorrhage<\/text>\n <text x=\"227\" y=\"89\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">Hypoglycaemia,<\/text>\n <text x=\"227\" y=\"101\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">hypocalcaemia<\/text>\n <text x=\"227\" y=\"119\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">Early-onset sepsis<\/text>\n <text x=\"227\" y=\"131\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">(GBS meningitis)<\/text>\n <text x=\"227\" y=\"149\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">Drug withdrawal,<\/text>\n <text x=\"227\" y=\"161\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">pyridoxine dependency<\/text>\n \n <text x=\"375\" y=\"59\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">HIE (ongoing),<\/text>\n <text x=\"375\" y=\"71\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">cerebral infarction<\/text>\n <text x=\"375\" y=\"89\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">Hypocalcaemia,<\/text>\n <text x=\"375\" y=\"101\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">hypomagnesaemia<\/text>\n <text x=\"375\" y=\"119\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">Bacterial meningitis<\/text>\n <text x=\"375\" y=\"131\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">(any organism)<\/text>\n <text x=\"375\" y=\"149\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">Benign neonatal<\/text>\n <text x=\"375\" y=\"161\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">convulsions (day 5)<\/text>\n \n <text x=\"533\" y=\"59\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">Cerebral infarction,<\/text>\n <text x=\"533\" y=\"71\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">cortical dysplasia<\/text>\n <text x=\"533\" y=\"89\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">Late hypocalcaemia<\/text>\n <text x=\"533\" y=\"101\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">(cow's milk formula)<\/text>\n <text x=\"533\" y=\"119\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">HSV encephalitis<\/text>\n <text x=\"533\" y=\"131\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">(consider aciclovir)<\/text>\n <text x=\"533\" y=\"149\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">Inborn errors of<\/text>\n <text x=\"533\" y=\"161\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">metabolism<\/text>\n \n <line x1=\"148\" y1=\"8\" x2=\"148\" y2=\"168\" stroke=\"#EDD8D8\" stroke-width=\"1\"\/>\n <line x1=\"296\" y1=\"8\" x2=\"296\" y2=\"168\" stroke=\"#EDD8D8\" stroke-width=\"1\"\/>\n <line x1=\"444\" y1=\"8\" x2=\"444\" y2=\"168\" stroke=\"#EDD8D8\" stroke-width=\"1\"\/>\n \n <line x1=\"0\" y1=\"44\" x2=\"620\" y2=\"44\" stroke=\"#EDD8D8\" stroke-width=\"0.5\"\/>\n <line x1=\"0\" y1=\"74\" x2=\"620\" y2=\"74\" stroke=\"#EDD8D8\" stroke-width=\"0.5\"\/>\n <line x1=\"0\" y1=\"104\" x2=\"620\" y2=\"104\" stroke=\"#EDD8D8\" stroke-width=\"0.5\"\/>\n <line x1=\"0\" y1=\"134\" x2=\"620\" y2=\"134\" stroke=\"#EDD8D8\" stroke-width=\"0.5\"\/>\n <\/svg>\n <figcaption>\n Causes of neonatal seizures stratified by time of onset.\n <strong>HIE<\/strong> dominates the first 24 hours.\n <strong>Metabolic causes<\/strong> (hypoglycaemia, hypocalcaemia) are correctable and must be excluded immediately in every case.\n <strong>HSV encephalitis<\/strong> presenting after 72 hours warrants empirical aciclovir until excluded.\n <strong>Pyridoxine dependency<\/strong> is rare but should be considered in refractory seizures at any age with no other cause found.\n <\/figcaption>\n <\/figure>\n<\/div>\n\n\n\n<div id=\"neo05\">\n\n <div class=\"mr-header\">\n <div class=\"mr-eyebrow\">Morning Rounds · Neonatology Series<\/div>\n <div class=\"mr-title\">\n Neonatal Seizures<br><em>Clinical Reasoning<\/em>\n <\/div>\n <div class=\"mr-subtitle\">Five cases · Read carefully · Trust your instinct<\/div>\n <div class=\"mr-chips\">\n <span class=\"mr-chip\">5 Cases<\/span>\n <span class=\"mr-chip\">+4 \/ −1 scoring<\/span>\n <span class=\"mr-chip\">Options reshuffled<\/span>\n <\/div>\n <\/div>\n\n <div class=\"mr-sentinel\" id=\"neo05-sentinel\"><\/div>\n\n <div class=\"mr-progress\" id=\"neo05-progress\">\n <div class=\"mr-prog-inner\">\n <div class=\"mr-pips\" id=\"neo05-pips\"><\/div>\n <\/div>\n <\/div>\n\n <div class=\"mr-body\">\n <div id=\"neo05-cases\"><\/div>\n\n <div class=\"mr-submit-wrap\">\n <button class=\"mr-btn\" id=\"neo05-submit\">Submit for Debrief<\/button>\n <\/div>\n\n <div class=\"mr-score\" id=\"neo05-score\">\n <div class=\"mr-score-in\">\n <div class=\"mr-score-ey\">Round Complete<\/div>\n <div class=\"mr-ring\" id=\"neo05-ring\">\n <div class=\"mr-ring-in\">\n <span class=\"mr-ring-pct\" id=\"neo05-pct\">0%<\/span>\n <span class=\"mr-ring-sub\">net<\/span>\n <\/div>\n <\/div>\n <div class=\"mr-score-title\">Your Debrief<\/div>\n <div class=\"mr-score-net\" id=\"neo05-net\"><\/div>\n <div class=\"mr-verdict\" id=\"neo05-verdict\"><\/div>\n <div class=\"mr-bands\">\n <span class=\"mr-band mr-band-c\" id=\"neo05-ct-c\"><\/span>\n <span class=\"mr-band mr-band-w\" id=\"neo05-ct-w\"><\/span>\n <span class=\"mr-band mr-band-s\" id=\"neo05-ct-s\"><\/span>\n <\/div>\n <button class=\"mr-retry\" id=\"neo05-retry\">↻ New Round<\/button>\n <\/div>\n <\/div>\n\n <\/div>\n<\/div>\n\n\n<script>\n(function () {\n 'use strict';\n\n var NS = 'neo05';\n var TOTAL = 5;\n var MAX = 20;\n var LTRS = ['A','B','C','D'];\n\n var QS = [\n\n {\n id: 1,\n tag: 'Neonatal Seizures — Cause by Time of Onset',\n stem: 'A <strong>term neonate<\/strong> develops <strong>subtle seizures at 10 hours of life<\/strong> — repetitive lip-smacking, cycling movements of the legs, and apnoeic episodes. The delivery was complicated by a tight nuchal cord and prolonged second stage. Blood glucose is 3.2 mmol\/L; serum calcium is normal. What is the single most likely cause?',\n correct: 'Hypoxic-ischaemic encephalopathy (HIE) — the commonest cause of neonatal seizures in the first 24 hours',\n opts: [\n 'Hypoxic-ischaemic encephalopathy (HIE) — the commonest cause of neonatal seizures in the first 24 hours',\n 'Hypoglycaemia — blood glucose of 3.2 mmol\/L is below the neonatal seizure threshold',\n 'Benign neonatal convulsions — typically present on day 5 with self-limiting clonic jerks',\n 'HSV encephalitis — the commonest viral cause of seizures in the first 12 hours of life'\n ],\n exp: '<strong>HIE is the commonest cause of neonatal seizures<\/strong>, accounting for roughly 50% of cases, and characteristically presents in the <strong>first 24 hours<\/strong> of life following a hypoxic event at delivery. Subtle seizures — lip-smacking, cycling, apnoea, eye deviation — are the most common seizure type in term neonates and are easily missed clinically. Blood glucose of 3.2 mmol\/L is above the intervention threshold (2.6 mmol\/L for at-risk neonates) and is not causative here. Benign neonatal convulsions (fifth-day fits) characteristically occur around day 5. HSV encephalitis typically presents after 72 hours. The time-of-onset framework is the key diagnostic anchor for neonatal seizures.',\n imgId: 'neo05-img1'\n },\n\n {\n id: 2,\n tag: 'Neonatal Seizures — Subtle vs Clonic vs Tonic',\n stem: 'A <strong>32-week preterm neonate<\/strong> on day 3 of life develops <strong>sustained deviation of both eyes to the left, followed by rhythmic jerking of the left arm<\/strong>. The movements are not suppressible by repositioning the limb. EEG shows an electrographic seizure correlating with the clinical event. How should this seizure type be classified?',\n correct: 'Focal clonic seizure — rhythmic jerking of one limb, EEG correlate present, not suppressible',\n opts: [\n 'Focal clonic seizure — rhythmic jerking of one limb, EEG correlate present, not suppressible',\n 'Subtle seizure — eye deviation and limb jerking without EEG correlate are always classified as subtle',\n 'Jitteriness — rhythmic movements in preterm neonates are physiological tremors, not seizures',\n 'Tonic seizure — sustained posturing of a limb with EEG correlate defines a tonic event'\n ],\n exp: '<strong>Classification of neonatal seizures<\/strong> matters because it guides urgency and prognosis. <strong>Focal clonic<\/strong> seizures are rhythmic, repetitive jerking of one limb or one side, with an EEG correlate — they are <em>not suppressible<\/em> by repositioning (unlike jitteriness). <strong>Subtle seizures<\/strong> include eye deviation, cycling, lip-smacking, and apnoea; some have EEG correlates and some do not. <strong>Tonic seizures<\/strong> involve sustained posturing (flexion or extension) of limbs or trunk. The critical clinical distinction from <strong>jitteriness<\/strong>: jitteriness is stimulus-sensitive, suppressed by gentle restraint, has no EEG correlate, and has no eye movement component. Focal clonic seizures in a preterm neonate at day 3 raise suspicion of cerebral infarction.',\n imgId: null\n },\n\n {\n id: 3,\n tag: 'Neonatal Seizures — Late Hypocalcaemia',\n stem: 'A <strong>12-day-old term male<\/strong> presents with <strong>multifocal clonic seizures<\/strong>. He has been exclusively formula-fed since birth. His mother is a vegetarian with low sun exposure. Investigations show: serum calcium <strong>1.6 mmol\/L<\/strong>, phosphate <strong>3.2 mmol\/L<\/strong> (elevated), magnesium normal, glucose normal. What is the most likely diagnosis and its mechanism?',\n correct: 'Late neonatal hypocalcaemia from high-phosphate cow\\'s milk formula — excess phosphate suppresses parathyroid hormone and reduces calcium',\n opts: [\n 'Late neonatal hypocalcaemia from high-phosphate cow\\'s milk formula — excess phosphate suppresses parathyroid hormone and reduces calcium',\n 'Hypomagnesaemia — elevated phosphate is the primary cause of neonatal seizures in formula-fed infants',\n 'DiGeorge syndrome — absence of parathyroid glands causing hypocalcaemia with normal phosphate',\n 'Vitamin D deficiency rickets — presents at 12 days with seizures and elevated phosphate'\n ],\n exp: '<strong>Late neonatal hypocalcaemia<\/strong> (after day 4, typically day 5–14) has a distinct mechanism from early hypocalcaemia. Standard cow\\'s milk-based formula has a <strong>high phosphate load<\/strong>; the immature neonatal kidney cannot excrete this efficiently, so hyperphosphataemia develops → phosphate binds ionised calcium → hypocalcaemia → seizures. The pattern: <strong>low calcium + high phosphate + normal magnesium<\/strong> in an otherwise well formula-fed baby is the classic fingerprint. Treatment is IV or oral calcium gluconate. <strong>DiGeorge syndrome<\/strong> also causes hypocalcaemia but phosphate is elevated due to absent PTH, not formula — it is typically associated with cardiac defects and dysmorphic features. This presentation is not DiGeorge; the formula link is the discriminator.',\n imgId: null\n },\n\n {\n id: 4,\n tag: 'Neonatal Seizures — HSV Encephalitis',\n stem: 'A <strong>9-day-old term neonate<\/strong> presents with <strong>fever, irritability, focal seizures, and CSF pleocytosis<\/strong> (WBC 62 cells, predominantly lymphocytes; protein 1.8 g\/L; glucose ratio 0.48). The mother had a history of genital herpes but no visible lesions at delivery. CSF HSV PCR is pending. What is the correct immediate management?',\n correct: 'Start IV aciclovir 20 mg\/kg every 8 hours immediately — do not await PCR result; delay increases mortality and morbidity',\n opts: [\n 'Start IV aciclovir 20 mg\/kg every 8 hours immediately — do not await PCR result; delay increases mortality and morbidity',\n 'Await CSF HSV PCR result before starting aciclovir — empirical treatment is not justified without microbiological confirmation',\n 'Start IV ceftriaxone alone — lymphocytic CSF pleocytosis indicates bacterial meningitis treatable with cephalosporins',\n 'Start IV aciclovir only if skin vesicles are present — HSV encephalitis without cutaneous lesions is exceedingly rare'\n ],\n exp: '<strong>Neonatal HSV encephalitis<\/strong> is a medical emergency with untreated mortality exceeding 50%. HSV-2 is transmitted perinatally; paradoxically, neonates born to mothers with <em>primary<\/em> HSV (who lack antibodies) are at highest risk even without visible lesions at delivery. Presentation at 7–14 days with fever, seizures, and lymphocytic CSF pleocytosis is the classic picture. <strong>IV aciclovir 20 mg\/kg 8-hourly must be started immediately<\/strong> — PCR confirmation takes hours and must not delay treatment. Up to <strong>30–40% of neonatal HSV CNS disease occurs without skin vesicles<\/strong>, making the clinical diagnosis challenging. Treatment duration for CNS disease is <strong>21 days<\/strong>. Even with treatment, neurological sequelae are common in encephalitic HSV.',\n imgId: null\n },\n\n {\n id: 5,\n tag: 'Neonatal Seizures — Pyridoxine Dependency',\n stem: 'A <strong>term neonate<\/strong> develops <strong>refractory seizures from 2 hours of life<\/strong>. Glucose, calcium, magnesium, and sodium are all normal. CSF is normal. Blood culture and CSF culture are negative. Cranial ultrasound shows no structural abnormality. Phenobarbitone 40 mg\/kg (maximum loading dose) fails to control the seizures. EEG shows burst-suppression. A trial of <strong>IV pyridoxine 100 mg<\/strong> is administered and the seizures cease within minutes and the EEG normalises. What is the diagnosis and its biochemical basis?',\n correct: 'Pyridoxine-dependent epilepsy — deficiency of ALDH7A1 causes accumulation of Δ1-piperideine-6-carboxylate, inactivating pyridoxal phosphate and blocking GABA synthesis',\n opts: [\n 'Pyridoxine-dependent epilepsy — deficiency of ALDH7A1 causes accumulation of Δ1-piperideine-6-carboxylate, inactivating pyridoxal phosphate and blocking GABA synthesis',\n 'Biotinidase deficiency — biotin-responsive seizures that respond to pyridoxine as a cross-reactive cofactor',\n 'Benign neonatal epilepsy — KCNQ2 channel mutation causing self-limiting seizures responsive to any anticonvulsant',\n 'Folinic acid-responsive seizures — a separate disorder with identical presentation but responding only to folinic acid, not pyridoxine'\n ],\n exp: '<strong>Pyridoxine-dependent epilepsy (PDE)<\/strong> is a rare autosomal recessive disorder caused by mutations in <strong>ALDH7A1<\/strong> (antiquitin), encoding an enzyme in the lysine degradation pathway. Deficiency leads to accumulation of <strong>Δ1-piperideine-6-carboxylate (P6C)<\/strong>, which reacts with and inactivates <strong>pyridoxal-5-phosphate (PLP)<\/strong> — the active form of vitamin B6 and an essential cofactor for glutamic acid decarboxylase (GAD), the enzyme that synthesises <strong>GABA<\/strong>. Without GABA, neuronal inhibition collapses and refractory seizures result. The diagnostic clue is <strong>refractory neonatal seizures with normal metabolic screen, normal imaging, and failure of conventional anticonvulsants<\/strong> — the dramatic response to IV pyridoxine confirms the diagnosis. Plasma and CSF pipecolic acid and urinary α-AASA are confirmatory biomarkers. Treatment is lifelong oral pyridoxine.',\n imgId: null\n }\n\n ];\n\n\n var answers = {};\n var answered = 0;\n var shuffled = {};\n var done = false;\n\n function byId(id) { return document.getElementById(id); }\n function gid(suffix) { return byId(NS + '-' + suffix); }\n\n function shuffleArr(arr) {\n var a = arr.slice(), i, j, tmp;\n for (i = a.length - 1; i > 0; i--) {\n j = Math.floor(Math.random() * (i + 1));\n tmp = a[i]; a[i] = a[j]; a[j] = tmp;\n }\n return a;\n }\n\n function countVal(val) {\n var k, n = 0;\n for (k in answers) {\n if (answers.hasOwnProperty(k) && answers[k] === val) n++;\n }\n return n;\n }\n\n function buildPips() {\n var cont = gid('pips'), i, q, wLine, wPip, line, pip;\n cont.innerHTML = '';\n for (i = 0; i < QS.length; i++) {\n q = QS[i];\n if (i > 0) {\n wLine = document.createElement('div');\n wLine.className = 'mr-pip-wrap';\n line = document.createElement('div');\n line.className = 'mr-pip-line';\n line.id = NS + '-pl' + q.id;\n wLine.appendChild(line);\n cont.appendChild(wLine);\n }\n wPip = document.createElement('div');\n wPip.className = 'mr-pip-wrap';\n pip = document.createElement('div');\n pip.className = 'mr-pip';\n pip.id = NS + '-pip' + q.id;\n pip.textContent = String(q.id);\n wPip.appendChild(pip);\n cont.appendChild(wPip);\n }\n }\n\n function build() {\n var cont, i, q, opts, card, top, numDiv, meta, tag, stem,\n rule, optsDiv, expDiv, lbl, txt, imgDiv, imgSrc, j,\n optEl, ltrSpan, txtSpan;\n\n cont = gid('cases');\n cont.innerHTML = '';\n answers = {}; answered = 0; shuffled = {}; done = false;\n gid('score').style.display = 'none';\n buildPips();\n\n for (i = 0; i < QS.length; i++) {\n q = QS[i];\n opts = shuffleArr(q.opts);\n shuffled[q.id] = opts;\n\n card = document.createElement('div');\n card.className = 'mr-case';\n\n top = document.createElement('div');\n top.className = 'mr-case-top';\n\n numDiv = document.createElement('div');\n numDiv.className = 'mr-num';\n numDiv.textContent = q.id < 10 ? 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4,Georgia,serif\" font-size=\"10\" font-weight=\"700\" fill=\"#5C1E1E\">Onset<\/text>\n <text x=\"227\" y=\"27\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" font-weight=\"700\" fill=\"#FFFAFA\">0 – 24 h<\/text>\n <text x=\"375\" y=\"27\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" font-weight=\"700\" fill=\"#FFFAFA\">24 – 72 h<\/text>\n <text x=\"533\" y=\"27\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" font-weight=\"700\" fill=\"#FFFAFA\">72 h – 1 week<\/text>\n \n <rect x=\"0\" y=\"44\" width=\"620\" height=\"30\" fill=\"#FDF4F4\"\/>\n <rect x=\"0\" y=\"74\" width=\"620\" height=\"30\" fill=\"#FFFAFA\"\/>\n <rect x=\"0\" y=\"104\" width=\"620\" height=\"30\" fill=\"#FDF4F4\"\/>\n <rect x=\"0\" y=\"134\" width=\"620\" height=\"30\" fill=\"#FFFAFA\"\/>\n \n <text x=\"6\" y=\"65\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"9\" font-weight=\"700\" fill=\"#9A7070\">Common<\/text>\n <text x=\"6\" y=\"95\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"9\" font-weight=\"700\" fill=\"#9A7070\">Metabolic<\/text>\n <text x=\"6\" y=\"125\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"9\" font-weight=\"700\" fill=\"#9A7070\">Infective<\/text>\n <text x=\"6\" y=\"155\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"9\" font-weight=\"700\" fill=\"#9A7070\">Other<\/text>\n \n <text x=\"227\" y=\"59\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">HIE (commonest)<\/text>\n <text x=\"227\" y=\"71\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">intracranial haemorrhage<\/text>\n <text x=\"227\" y=\"89\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">Hypoglycaemia,<\/text>\n <text x=\"227\" y=\"101\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">hypocalcaemia<\/text>\n <text x=\"227\" y=\"119\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">Early-onset sepsis<\/text>\n <text x=\"227\" y=\"131\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">(GBS meningitis)<\/text>\n <text x=\"227\" y=\"149\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">Drug withdrawal,<\/text>\n <text x=\"227\" y=\"161\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">pyridoxine dependency<\/text>\n \n <text x=\"375\" y=\"59\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">HIE (ongoing),<\/text>\n <text x=\"375\" y=\"71\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">cerebral infarction<\/text>\n <text x=\"375\" y=\"89\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">Hypocalcaemia,<\/text>\n <text x=\"375\" y=\"101\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">hypomagnesaemia<\/text>\n <text x=\"375\" y=\"119\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">Bacterial meningitis<\/text>\n <text x=\"375\" y=\"131\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">(any organism)<\/text>\n <text x=\"375\" y=\"149\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">Benign neonatal<\/text>\n <text x=\"375\" y=\"161\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">convulsions (day 5)<\/text>\n \n <text x=\"533\" y=\"59\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">Cerebral infarction,<\/text>\n <text x=\"533\" y=\"71\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">cortical dysplasia<\/text>\n <text x=\"533\" y=\"89\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">Late hypocalcaemia<\/text>\n <text x=\"533\" y=\"101\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">(cow's milk formula)<\/text>\n <text x=\"533\" y=\"119\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">HSV encephalitis<\/text>\n <text x=\"533\" y=\"131\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">(consider aciclovir)<\/text>\n <text x=\"533\" y=\"149\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">Inborn errors of<\/text>\n <text x=\"533\" y=\"161\" text-anchor=\"middle\" font-family=\"Source Serif 4,Georgia,serif\" font-size=\"10\" fill=\"#2A1010\">metabolism<\/text>\n \n <line x1=\"148\" y1=\"8\" x2=\"148\" y2=\"168\" stroke=\"#EDD8D8\" stroke-width=\"1\"\/>\n <line x1=\"296\" y1=\"8\" x2=\"296\" y2=\"168\" stroke=\"#EDD8D8\" stroke-width=\"1\"\/>\n <line x1=\"444\" y1=\"8\" x2=\"444\" y2=\"168\" stroke=\"#EDD8D8\" stroke-width=\"1\"\/>\n \n <line x1=\"0\" y1=\"44\" x2=\"620\" y2=\"44\" stroke=\"#EDD8D8\" stroke-width=\"0.5\"\/>\n <line x1=\"0\" y1=\"74\" x2=\"620\" y2=\"74\" stroke=\"#EDD8D8\" stroke-width=\"0.5\"\/>\n <line x1=\"0\" y1=\"104\" x2=\"620\" y2=\"104\" stroke=\"#EDD8D8\" stroke-width=\"0.5\"\/>\n <line x1=\"0\" y1=\"134\" x2=\"620\" y2=\"134\" stroke=\"#EDD8D8\" stroke-width=\"0.5\"\/>\n <\/svg>\n <figcaption>\n Causes of neonatal seizures stratified by time of onset.\n <strong>HIE<\/strong> dominates the first 24 hours.\n <strong>Metabolic causes<\/strong> (hypoglycaemia, hypocalcaemia) are correctable and must be excluded immediately in every case.\n <strong>HSV encephalitis<\/strong> presenting after 72 hours warrants empirical aciclovir until excluded.\n <strong>Pyridoxine dependency<\/strong> is rare but should be considered in refractory seizures at any age with no other cause found.\n <\/figcaption>\n <\/figure>\n<\/div>\n\n\n\n<div id=\"neo05\">\n\n <div class=\"mr-header\">\n <div class=\"mr-eyebrow\">Morning Rounds · Neonatology Series<\/div>\n <div class=\"mr-title\">\n Neonatal Seizures<br><em>Clinical Reasoning<\/em>\n <\/div>\n <div class=\"mr-subtitle\">Five cases · Read carefully · Trust your instinct<\/div>\n <div class=\"mr-chips\">\n <span class=\"mr-chip\">5 Cases<\/span>\n <span class=\"mr-chip\">+4 \/ −1 scoring<\/span>\n <span class=\"mr-chip\">Options reshuffled<\/span>\n <\/div>\n <\/div>\n\n <div class=\"mr-sentinel\" id=\"neo05-sentinel\"><\/div>\n\n <div class=\"mr-progress\" id=\"neo05-progress\">\n <div class=\"mr-prog-inner\">\n <div class=\"mr-pips\" id=\"neo05-pips\"><\/div>\n <\/div>\n <\/div>\n\n <div class=\"mr-body\">\n <div id=\"neo05-cases\"><\/div>\n\n <div class=\"mr-submit-wrap\">\n <button class=\"mr-btn\" id=\"neo05-submit\">Submit for Debrief<\/button>\n <\/div>\n\n <div class=\"mr-score\" id=\"neo05-score\">\n <div class=\"mr-score-in\">\n <div class=\"mr-score-ey\">Round Complete<\/div>\n <div class=\"mr-ring\" id=\"neo05-ring\">\n <div class=\"mr-ring-in\">\n <span class=\"mr-ring-pct\" id=\"neo05-pct\">0%<\/span>\n <span class=\"mr-ring-sub\">net<\/span>\n <\/div>\n <\/div>\n <div class=\"mr-score-title\">Your Debrief<\/div>\n <div class=\"mr-score-net\" id=\"neo05-net\"><\/div>\n <div class=\"mr-verdict\" id=\"neo05-verdict\"><\/div>\n <div class=\"mr-bands\">\n <span class=\"mr-band mr-band-c\" id=\"neo05-ct-c\"><\/span>\n <span class=\"mr-band mr-band-w\" id=\"neo05-ct-w\"><\/span>\n <span class=\"mr-band mr-band-s\" id=\"neo05-ct-s\"><\/span>\n <\/div>\n <button class=\"mr-retry\" id=\"neo05-retry\">↻ New Round<\/button>\n <\/div>\n <\/div>\n\n <\/div>\n<\/div>\n\n\n<script>\n(function () {\n 'use strict';\n\n var NS = 'neo05';\n var TOTAL = 5;\n var MAX = 20;\n var LTRS = ['A','B','C','D'];\n\n var QS = [\n\n {\n id: 1,\n tag: 'Neonatal Seizures — Cause by Time of Onset',\n stem: 'A <strong>term neonate<\/strong> develops <strong>subtle seizures at 10 hours of life<\/strong> — repetitive lip-smacking, cycling movements of the legs, and apnoeic episodes. The delivery was complicated by a tight nuchal cord and prolonged second stage. Blood glucose is 3.2 mmol\/L; serum calcium is normal. What is the single most likely cause?',\n correct: 'Hypoxic-ischaemic encephalopathy (HIE) — the commonest cause of neonatal seizures in the first 24 hours',\n opts: [\n 'Hypoxic-ischaemic encephalopathy (HIE) — the commonest cause of neonatal seizures in the first 24 hours',\n 'Hypoglycaemia — blood glucose of 3.2 mmol\/L is below the neonatal seizure threshold',\n 'Benign neonatal convulsions — typically present on day 5 with self-limiting clonic jerks',\n 'HSV encephalitis — the commonest viral cause of seizures in the first 12 hours of life'\n ],\n exp: '<strong>HIE is the commonest cause of neonatal seizures<\/strong>, accounting for roughly 50% of cases, and characteristically presents in the <strong>first 24 hours<\/strong> of life following a hypoxic event at delivery. Subtle seizures — lip-smacking, cycling, apnoea, eye deviation — are the most common seizure type in term neonates and are easily missed clinically. Blood glucose of 3.2 mmol\/L is above the intervention threshold (2.6 mmol\/L for at-risk neonates) and is not causative here. Benign neonatal convulsions (fifth-day fits) characteristically occur around day 5. HSV encephalitis typically presents after 72 hours. The time-of-onset framework is the key diagnostic anchor for neonatal seizures.',\n imgId: 'neo05-img1'\n },\n\n {\n id: 2,\n tag: 'Neonatal Seizures — Subtle vs Clonic vs Tonic',\n stem: 'A <strong>32-week preterm neonate<\/strong> on day 3 of life develops <strong>sustained deviation of both eyes to the left, followed by rhythmic jerking of the left arm<\/strong>. The movements are not suppressible by repositioning the limb. EEG shows an electrographic seizure correlating with the clinical event. How should this seizure type be classified?',\n correct: 'Focal clonic seizure — rhythmic jerking of one limb, EEG correlate present, not suppressible',\n opts: [\n 'Focal clonic seizure — rhythmic jerking of one limb, EEG correlate present, not suppressible',\n 'Subtle seizure — eye deviation and limb jerking without EEG correlate are always classified as subtle',\n 'Jitteriness — rhythmic movements in preterm neonates are physiological tremors, not seizures',\n 'Tonic seizure — sustained posturing of a limb with EEG correlate defines a tonic event'\n ],\n exp: '<strong>Classification of neonatal seizures<\/strong> matters because it guides urgency and prognosis. <strong>Focal clonic<\/strong> seizures are rhythmic, repetitive jerking of one limb or one side, with an EEG correlate — they are <em>not suppressible<\/em> by repositioning (unlike jitteriness). <strong>Subtle seizures<\/strong> include eye deviation, cycling, lip-smacking, and apnoea; some have EEG correlates and some do not. <strong>Tonic seizures<\/strong> involve sustained posturing (flexion or extension) of limbs or trunk. The critical clinical distinction from <strong>jitteriness<\/strong>: jitteriness is stimulus-sensitive, suppressed by gentle restraint, has no EEG correlate, and has no eye movement component. Focal clonic seizures in a preterm neonate at day 3 raise suspicion of cerebral infarction.',\n imgId: null\n },\n\n {\n id: 3,\n tag: 'Neonatal Seizures — Late Hypocalcaemia',\n stem: 'A <strong>12-day-old term male<\/strong> presents with <strong>multifocal clonic seizures<\/strong>. He has been exclusively formula-fed since birth. His mother is a vegetarian with low sun exposure. Investigations show: serum calcium <strong>1.6 mmol\/L<\/strong>, phosphate <strong>3.2 mmol\/L<\/strong> (elevated), magnesium normal, glucose normal. What is the most likely diagnosis and its mechanism?',\n correct: 'Late neonatal hypocalcaemia from high-phosphate cow\\'s milk formula — excess phosphate suppresses parathyroid hormone and reduces calcium',\n opts: [\n 'Late neonatal hypocalcaemia from high-phosphate cow\\'s milk formula — excess phosphate suppresses parathyroid hormone and reduces calcium',\n 'Hypomagnesaemia — elevated phosphate is the primary cause of neonatal seizures in formula-fed infants',\n 'DiGeorge syndrome — absence of parathyroid glands causing hypocalcaemia with normal phosphate',\n 'Vitamin D deficiency rickets — presents at 12 days with seizures and elevated phosphate'\n ],\n exp: '<strong>Late neonatal hypocalcaemia<\/strong> (after day 4, typically day 5–14) has a distinct mechanism from early hypocalcaemia. Standard cow\\'s milk-based formula has a <strong>high phosphate load<\/strong>; the immature neonatal kidney cannot excrete this efficiently, so hyperphosphataemia develops → phosphate binds ionised calcium → hypocalcaemia → seizures. The pattern: <strong>low calcium + high phosphate + normal magnesium<\/strong> in an otherwise well formula-fed baby is the classic fingerprint. Treatment is IV or oral calcium gluconate. <strong>DiGeorge syndrome<\/strong> also causes hypocalcaemia but phosphate is elevated due to absent PTH, not formula — it is typically associated with cardiac defects and dysmorphic features. This presentation is not DiGeorge; the formula link is the discriminator.',\n imgId: null\n },\n\n {\n id: 4,\n tag: 'Neonatal Seizures — HSV Encephalitis',\n stem: 'A <strong>9-day-old term neonate<\/strong> presents with <strong>fever, irritability, focal seizures, and CSF pleocytosis<\/strong> (WBC 62 cells, predominantly lymphocytes; protein 1.8 g\/L; glucose ratio 0.48). The mother had a history of genital herpes but no visible lesions at delivery. CSF HSV PCR is pending. What is the correct immediate management?',\n correct: 'Start IV aciclovir 20 mg\/kg every 8 hours immediately — do not await PCR result; delay increases mortality and morbidity',\n opts: [\n 'Start IV aciclovir 20 mg\/kg every 8 hours immediately — do not await PCR result; delay increases mortality and morbidity',\n 'Await CSF HSV PCR result before starting aciclovir — empirical treatment is not justified without microbiological confirmation',\n 'Start IV ceftriaxone alone — lymphocytic CSF pleocytosis indicates bacterial meningitis treatable with cephalosporins',\n 'Start IV aciclovir only if skin vesicles are present — HSV encephalitis without cutaneous lesions is exceedingly rare'\n ],\n exp: '<strong>Neonatal HSV encephalitis<\/strong> is a medical emergency with untreated mortality exceeding 50%. HSV-2 is transmitted perinatally; paradoxically, neonates born to mothers with <em>primary<\/em> HSV (who lack antibodies) are at highest risk even without visible lesions at delivery. Presentation at 7–14 days with fever, seizures, and lymphocytic CSF pleocytosis is the classic picture. <strong>IV aciclovir 20 mg\/kg 8-hourly must be started immediately<\/strong> — PCR confirmation takes hours and must not delay treatment. Up to <strong>30–40% of neonatal HSV CNS disease occurs without skin vesicles<\/strong>, making the clinical diagnosis challenging. Treatment duration for CNS disease is <strong>21 days<\/strong>. Even with treatment, neurological sequelae are common in encephalitic HSV.',\n imgId: null\n },\n\n {\n id: 5,\n tag: 'Neonatal Seizures — Pyridoxine Dependency',\n stem: 'A <strong>term neonate<\/strong> develops <strong>refractory seizures from 2 hours of life<\/strong>. Glucose, calcium, magnesium, and sodium are all normal. CSF is normal. Blood culture and CSF culture are negative. Cranial ultrasound shows no structural abnormality. Phenobarbitone 40 mg\/kg (maximum loading dose) fails to control the seizures. EEG shows burst-suppression. A trial of <strong>IV pyridoxine 100 mg<\/strong> is administered and the seizures cease within minutes and the EEG normalises. What is the diagnosis and its biochemical basis?',\n correct: 'Pyridoxine-dependent epilepsy — deficiency of ALDH7A1 causes accumulation of Δ1-piperideine-6-carboxylate, inactivating pyridoxal phosphate and blocking GABA synthesis',\n opts: [\n 'Pyridoxine-dependent epilepsy — deficiency of ALDH7A1 causes accumulation of Δ1-piperideine-6-carboxylate, inactivating pyridoxal phosphate and blocking GABA synthesis',\n 'Biotinidase deficiency — biotin-responsive seizures that respond to pyridoxine as a cross-reactive cofactor',\n 'Benign neonatal epilepsy — KCNQ2 channel mutation causing self-limiting seizures responsive to any anticonvulsant',\n 'Folinic acid-responsive seizures — a separate disorder with identical presentation but responding only to folinic acid, not pyridoxine'\n ],\n exp: '<strong>Pyridoxine-dependent epilepsy (PDE)<\/strong> is a rare autosomal recessive disorder caused by mutations in <strong>ALDH7A1<\/strong> (antiquitin), encoding an enzyme in the lysine degradation pathway. Deficiency leads to accumulation of <strong>Δ1-piperideine-6-carboxylate (P6C)<\/strong>, which reacts with and inactivates <strong>pyridoxal-5-phosphate (PLP)<\/strong> — the active form of vitamin B6 and an essential cofactor for glutamic acid decarboxylase (GAD), the enzyme that synthesises <strong>GABA<\/strong>. Without GABA, neuronal inhibition collapses and refractory seizures result. The diagnostic clue is <strong>refractory neonatal seizures with normal metabolic screen, normal imaging, and failure of conventional anticonvulsants<\/strong> — the dramatic response to IV pyridoxine confirms the diagnosis. Plasma and CSF pipecolic acid and urinary α-AASA are confirmatory biomarkers. 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