Neurology Development

Neurology development Brain development Continues until 10yrs old Neurogenesis – 1st neural tissue appears from d18 with neural crest à neural tube Rapid growth from 4-18w Differentiation – primitive neural cells à neurones & glia also w4-18 Proliferation – vast increase in cell number unto 18w (most of these later die with neuronal regression) Neuronal Migration – produced deep in brain & migrates to the cortex. Finished by w25 Neuronal regression – apoptosis ensures only functional neurones survive. Synapse development – each is in contact with upto 10,000 others. Learning à new synapses Myelination – glial cells rapidly grow from 24w. Myelination complete by approx 12y Dorsal induction – formation & migration of neural tube (4/40) à anterior tube = brain. Disorders à anencephaly, encephalocele, myelomeningocele & meningocele Ventral induction – development of ventral end of tube, esp cleavage to hemispheres & ventricles with thalamus & hypothalamus growth (5-6/40) Disorders à holoprosencephaly Timing of insults causing disability Prenatal 70-75% E.g. Downs, NTD, viral infection, IUGR, toxins & drugs Perinatal 20% (60% prem, 40% term) E.g. birth asphyxia, IVH, PVL, Ototoxic drugs, kernicterus, low BM Postnatal 5-10% E.g. hypothyroid, meningitis, inborn errors of metabolism, trauma Head shape and Size Microcephally = < 2 SD below mean Prognosis is usually poor Can be familial (constitutional) Primary (always small) Familial AR X-linked recessive Chromosomal (e.g. T13, T18) TORCH Maternal PKU Lissencephaly = “smooth brain” Fetal Alcohol Syn Secondary (grow normally to a point) IUGR Meningitis Hypoglycaemia Asphyxia Periventricular leucomalacia Macrocephally = > 2 SD above mean Differentials Large baby Benign familial Hydrocephalus Subdural effusions • • • Posterior fontanelle closes by 8/52 Ant fontanelle closes by 12-18 m Sutures fuse at approx. 6yrs Megaencephaly Anatomical – Sotos, Weavers, neurocutaneous syndromes Metabolic – alexanders, canavans, gutaric acid-uria type 1, storage disorders, leucodystrophies, skull vault disorders Hydrocephalus – can have normal OFC Imbalance of fluid production & absorption Dilated lateral ventricles Features Infant – increased rate of head growth, macrocephaly, splayed sutures, tense fontanelle, dilated scalp veins, vertical gaze paresis, sun setting eyes Older – headache, vomits, irritable, papilloedema, bilateral abducens palsy/paresis, lower limb spacticity & ataxia Non-obstructive – no interference with flow. Usually due to papilloma of choroid Obstructive – can be communicating / non-comunicating Non-communicating – little / no communication between ventricles & sub-archnoid space. 3 common sites of obstruction: • Aqueduct of Sylvius (stenosis / atresia) • Occlusion of foramina of Luschka & Magendi (basal adhesions / IVH) • Arnold-Chiari type II (secondary to spina bifida cystica) Communicating – CSF can escape but cannot be absorbed by arachnoid granulations (usually post meningitis / bleed) Of ventricular dilatation following IVH – 15% noncommunicating, 85% communicating Diagnosis – CUSS (antenatal / postnatal) Sunset appearance of the eyes= late sign of hydrocephalus & raised ICP = Downward gaze of eyes with sclera visible above iris due to pressure on cranial nerves Management – regular OFC measurements Shunting may be appropriate (VP) Otherwise palliative CSF tapping Craniosyntosis = premature closure of sutures Holoprosencephally = fused ventricles Failure of midline fusion à single cerebral ventricle Can have other midline defects e.g. eyes, lips, palate ½ have abnormal chromosome pattern (most commonly T13 or T18) Hydranencepaly – almost total loss of all cerebral substance due to vascular insult / infection after 12/40. Usually sparing of basal ganglia & cerebellum. Skull entirely filled with fluid at birth. May be normal / enlarged size. No Rx available Porencephaly – cystic cavities in one / both hemispheres. May / not communicate with ventricles. Can be congenital / acquired (meningitis / bleed / cerebral atrophy). Most commonly due to intraparenchymal haemorrhage = porencephalc cyst Lissencephally = no gyri. Abnormality of neuronal migration. Can be due to infection / asphyxia in 1st ½ of pregnancy. Brain appears smooth, often assoc microcephally +/- dysmorphism +/convulsions. The floppy infant Features Frog posture Non paralytic – weak infant with hypotonia & normal muscle. See limb movement with / without gravity following a stimulus E.g. asphyxia, Downs, Prader-willi, Skeletal & connective tissue disorders, drugs, benign congenital hypotonia Paralytic – weak infant with no limb movement E.g. SMA (werdnig-hoffman), congenital muscular dystrophy, congenital myopathy, congenital myotonic dystrophy, myasthenia gravis Causes by site Brain – asphyxia Spinal cord – trauma Anterior horn cell – Spinal Muscular Atrophy 1 (Werdnig Hoffman) Abnormality of anterior horn cells AR inheritance Profound weakness & hypotonia BUT expressive face due to sparing. Can have congenital contractures. No treatment. Die before 1y Nerve root – Brachial plexus injury – one arm only Peripheral nerve – trauma Neuromuscular junction – Myasthenia Gravis 90% in infants are due to maternal Ab therefore resolve within 6-12w Rarely can have spontaneous disease Absent reflexes but alert. Responsive to neostigmine Muscle – congenital muscular dystrophy AR inheritance Often born with severe contractures Improvement occurs with age Check CK ? Evolving CP – birth history, abnormal motor patterns, retain primitive reflexes, increased tone ? Hydrocephalus – monitor head size Investigations History Is the baby well Is the baby dysmorphic Neuro exam Pull to sit (head lag should resolve by 3-4m) Scarf sign (elbow to midline before resistance) Shoulder suspension (pick up under arms) Ventral suspension Strength = maximum voluntary movement resistance Reflexes Creatinine Phosphokinase – after 2/52 Electromyography Motor nerve conduction velocities Muscle biopsy Stiff Neck ? Meningitis ? polio ? retropharyngeal abscess ? Still’s disease (juvenile idiopathic arthritis) with C-spine involvement ? TB – via meningitis / Potts disease Movement disorders Chorea – fast, semi-rhythmic, non repetitive Huntingtons Neuroacanthocytosis Ataxia telangectasia Spinocerebellar ataxia Paroxysmal dyskinesogenic choreoathetosis SLE Wilsons Sydenhams Autoimmune process F>M, usually 8-9 yrs old 4-6 weeks post strep infection Can be hemichorea. Also prone to emotional lability, tics, OCD, mental health issues. 60-80% have cardiac involvement. Self limiting over 6-9 months. Recurrence in 20-50%. Ix: ASOT, ECHO, throat swab Rx: Haloperidol / valproate Drug induced – SSRI, TCA, OCP, Lithium, Dopamine agonists & blockers PANDAS – paediatric autoimmune neuropsychiatric disorder associated with streptococcus OCD & Tics. Onset 3yrs - puberty Athetosis – slow writhing Dystonia – abnormal tone à abnormal posture Improves in sleep SHOULDN’T have clonus (will in spasticity) Status dystonica can à rhabdomyolysis à renal failure. Treat with anaesthesia for as long as needed Benign paroxysmal torticorlis Dopa responsive dystonia Progressive difficulty walking Abnormal function of basal ganglia à dopamine imbalance AD form = GTP cyclohydrolase gene AR form = mutation in tyrosine hydrolase gene Symptoms begin around 7 years & initially mild (cramps after exercise) Gradually then features of parkinsonism (slow movements, instability / lack of balance) Better in morning, worsen with exertion Can mimic CP Therapeutic trial of levodopa CSF for mutations in GTP, CH1 and hTH genes Treatment with levodopa Secondary to infarction, metabolic errors etc Rx: Try dopa (may be dopa responsive) Myoclonus – jerks Tics – involuntary repetitive action. can persist in sleep. DO NOT interfere with voluntary movement Tremors – low amplitude peripheral shaking Resting tremors = poor prognosis, action based = usually benign Essential tremor = most common – genetic, M>F, bilat forearms. Stereotypes – repetitive movements, common in ASD Ataxia Acute Ingestion/ intoxication – primary differential if previously well child with drowsiness & lethargy Acute post infection cerebellar ataxia – most commonly varicella, maximum severity at onset, settles in 4-6/52 Encephalitis – usually brainstem SOL – can be posterior fossa tumour if shift of position / bleed / rapid growth ADEM (Acute disseminated encephalomyelitis) Usually 7-14d post infection / vaccine Polysymptomatic neuropathy and encephalopathy - Ataxia, paresis, CN palsies, fits usually hemispheres, can be just cerebellum 60-90% recovery, rarely fatal Can have residual sensory / motor / epilepsy / cognitive impairment / fatigue Rx: methypred, IVIg, Plasma exchange (remove inflame cytokines), if increasing pressure à craniotomy Basilar Migraine – BPV Rare Familial episodic ataxia Metabolic - mitochondrial, urea cycle, organic acidaemias Neuroblastoma – opsclonus-myoclonus syndrome Vertebrobasilar dissection – brain stem stroke MS Chronic / Progressive Brain tumour – cerebella astrocytoma, embryoma, ependymoma Developmental malformation of posterior fossa – cerebellar hypoplasia, dandy-walker malformation, chiari malformation Hereditary – freidrich’s ataxia (see below), ataxia telangectasia (see below), ataxia oculomotor apraxia, mitochondrial disorders Demyelination – MS Ataxic CP – due to malformation/damage to cerebellum e.g. dandy-walker syndrome (absence of foramen of majendie & luschka à dilatation of 4th ventricle Friedreich Ataxia ½ of all hereditary ataxia 9q13-q21.1 1/50,000 AR (can be AD) - usually homozygous for GAA triplet repeat Frataxin gene – Chr9 Affects central sensory pathways in posterior columns & spinocerebellar tracts of spinal cord + efferent cerebellar + corticospinal tracts Large myelinated peripheral sensory nerves also affected +/- Spinal cerebellar degeneration Onset typically around puberty (can be early / late) Legs > arms Sx Ataxia with broad based gait & clumsy (< 10 yrs) – lower limb > upper Progressive clumsiness & Clumsy gait Absent deep tendon reflexes, extensor plantars, +ve Rhombergs test Explosive dysarthric speech Loss of position & vibration sense due to degeneration of posterior column Can be weakness / sensory changes in distal extremities Pes cavus (plantar deformity), hammer toes, kyphoscoliosis Optic atrophy à visual + hearing impairment Cardiomyopathy Increasing handicap Can have scoliosis & hypertrophic cardiomyopathy O/E Nystagmus, truncal ataxia, dysarthria & dysmetria. Absent deep tendon reflexes, distal weakness. Loss of position & vibration sensation. Eye abnormalities in smooth pursuit and saccades Majority develop cardiomyopathy, optic atrophy, deafness and diabetes Ix MRI – atrophy of spinal cord – cerebral imaging is normal until advances disease Decreased sensory nerve action potentials – motor nerves unaffected ECHO – as most commonly die due to HOCM Prognosis Wheelchair by 10-15yrs post symptom onset Cognitive function unaffected Progressive à scoliosis & cardiomyopathy à death by 40-50yrs Many die of HOCM Ataxia Telangectasia AR – 11q22-23 – ATM protein for DNA repair Multisystem disease Most common recessive ataxia in < 5yrs Features: Progressive neurological impairment Cerebellar ataxia (once walking) Occulomotor apraxia & horizontal nystagmus Variable immunodeficiency (low IgA is most common à esp susceptible to sinus & lung infect) (decreased IgA, E & G) Impaired organ maturation Xray hypersensitivity Occular & cutaneous telangectasia by age 4 (conjunctiva, nasal bridge, ears & exposed limb surfaces) Predisposition to malignancy (esp leukaemia) Prognosis Truncal ataxia evident at < 3yrs Choreoathetosis + occulomotor apraxia Telangectasia usually develop after neuro Sx – seen on bulbar conjunctiva, neck & ears Normal intelligence Wheelchair by age 10 Average age at death = 20y, Usually due to lung infections / malignancy Diagnosis In infants can be confused with CP/infections/episodic/with occulomotor apraxia/rare mitochondrial disorders Check Serum AFP (raised) Karyotype – translocations on 7 & 14 B&T cell immune studies Can have defect in IgE, A & G2 Can test for DNA fragility Neural Tube Defects Prevalence – decreasing with folate & terminations Risk factors – previous affected children, valproate use Diagnosed - with US & raised AFP at 14-18/40 (only 1 in 10 of raised AFP = bifida) Prevention - Daily folic acid 4mg until wk 12 Anencephaly – forebrain is absent (insult before 24d gestation). Incompatible with life. à abortion / still birth / fetal death Encephalocele – failure of midline closure of skull (+/- herniation of brain). 80% are occipital. Occurs around 28d gestation. Prognosis depends on amount of brain in sac. Spina Bifida – developmental failure of fusion of vertebral column (+/- external sac / cord) 1/1000, 1/100 if previous affected sib / fetus, if 2nd infant affected = 1/30 Occulta – bifid vertebrae with overlying dimple / hairy patch. Can occur in upto 10% of population. Can have foot drop / urinary problems / tethered cord. Diastomyelia - bony spur dividing cord – may benefit from removal Cystica - menigocoele or myelomeningocoele Menigocoele – 20% of cystica. No herniation of neural tissue so no neuro deficit. Meningitis risk if CSF leak Myelomeningocoele – 80% of cystica. Cord involvement therefore neuro deficit 70% are lumbosacral 90% will have assoc hydrocephalus with Arnold-chiari malformation (prolapse of medulla, cerebellum & 4th ventricle through abnormal foramen magnum into cervical canal) Also assoc with ortho problems e.g. talipes, kyphosos etc Treatment Early neurosurgery (if appropriate) Ortho referral & Rx General surgery – continence Supportive – bed sores etc Genetic counselling Head Injury Traumatic brain injury is the commonest cause of acquired neuro-disability in childhood & = 1/3 of accidental death More common in boys Primary injuries Laceration – assoc with penetrating / rotational injuries Contusion – impact as coup / contre-coup Shearing – assoc with acceleration / deceleration, shearing through the corpus callosum, ass with petechial haemorrhages on MRI Concussion – transient membrane dysfunction assoc with short term deficit especially anterograde amnesia Extradural haematoma – skull #, lucid interval, seizures, focal neurology, anaemia & shock Subdural haematoma – usually NAI with retinal haemorrhages Subarachnoid haemorrhage – headache, neck stiffness, fever, retinal haemorrhages Secondary injuries Systemic hypoxia / hypotension from extracranial injuries Vascular injury / spasm – stretching / spasm à focal ischaemia Loss of autoregulation - à maldistribution of blood flow Uncontrolled epileptic seizures à imbalance of cerebral metabolism & perfusion Prognosis - 90% of functional recovery happens in 1st 6 months, with more gradual recovery over the next few yrs NB: subdural haematoma in children is assoc with inappropriate handling e.g. NAI Cerebral Palsy 2/1000 = commonest crippling handicap Definition - Permanent, non-progressive damage to the developing brain (conception - 5yrs) à motor disability & posture problems Causes: Congenital = 80% (cysts, aplasia, fusion defects, infection, hypoxic ischaemia), Perinatal = 10% (trauma, ischaemia), Types Post-natal = 10% (illness, meningitis, encephalopathy, NIA, RTA, near drowning, cardiac arrests, toxins, poisons, kernicterus, hypoglycaemia) Spastic (70%) – damage to motor cortex / corticospinal tract à clasp-knife hypertonia, brisk reflexes, ankle clonus, downward plantars, decerebrate position Spastic diplegia – mostly due to PVL Spastic hemiplegia – mostly due to MCA infarct Dystonia (10%) – basal ganglia / extrapyramidal system à irregular, involuntary movements, continuous or when voluntary, athetosis Most common cause if hyperbilirubinaemia Ataxic (10%) – cerebellum à hypotonic, weak, unco-ordinated & intension tremor Usually genetic Mixed (10%) – mixture of above Features – poor suckling, altered muscle tone, abnormal reflexes, irritable / drowsy, convulsions, hand preference before 1yr, persistence of primative reflexes Other problems – learning disorder (60%), epilepsy (30%), visual impairment (20%), squint (30%), speech disorders, poor school performance, behavioural disorders, orthopaedic deformities Management Botox (Botulinum toxin A) = chemically denervated muscle. Dose dependent paralysis of selected muscle groups – last 3-6m. Baclofen – gaba analogue à impedes excitatory neurotransmission @ spinal level. Oral – poor CSF penetration (poor lipid soluble) with T ½ = 3-4 hrs à QDS dosing à Intrathecal infusion Dorsal rhizotomy = partial cutting of specific sensory roots à affects reflex arc à decreased spacticity. Headache Commonly accompanies many febrile illnesses in childhood Migraine - Affects 5% at some time, often +ve FH Throbbing headache, visual disturbance, photophobia, nausea can à opthalamoplegia or hemiparesis NB: hemiplegic migraines are more common in children than adults and can à cerebral infarcts. Often +ve FH, AD inheritance of error in a Ca2+ channel Rx: 1st line: paracetamol @ onset, quiet, dark room (+ metoclopramide if N) 2nd line: diclofenac 3rd line: tryptans as rescue 4th Line: pizotifen prophylactic Sumatryptan 5HT1 agonist Used for migraine & cluster headaches Admin – Oral / SC after acute attack (S/C acts in 10-15min) Caution: coronary artery disease / hepatic impairment / pregnancy / breast feeding Contraindications: IHD, uncontrolled HTN SE – tingling, heat, heavy / pressure sensation, dizziness, flushing, weakness, fatigue, N&V Occular Headaches - From constant muscle activity to correct squint / refractive error Benign Intracranial Hypertension - ↑ICP of unknown origin Sx - vomiting, headache, papilloedema, can à CN VI palsy Causes - can be post viral illness, otitis media or sudden decrease in steroid therapy. Also Addison’s, obesity, oral contraceptives, pregnancy, head injury, Ix – Papilloedema, raised CSF opening pressure (>20) Rx aims to ↓ICP to prevent 2o optic atrophy. Can use medications to reduce CSF production Visual field assessment as increased pressure can lead to visual field loss Tension Headache Pressure like band / throbbing in nature Fatigue, dizziness, blurred vision Evidence of stress, improved on days away from stress Treatment difficult (MDT) Brain tumour Constant worsening headache with neurology Seizures & Syncope Seizure = ANY acute attack e.g. epileptic, CVA, syncope etc Epileptic seizure = manifestations of epileptic (excessive and/or hypersynchronous) usually self limited activity of neurones in the brain Epileptic disorder = predisposition to epileptic seizures = recurrent epileptic seizures Epilepsies – chronic recurrent epileptic seizures which can be considered epileptic disorders (chronic = not easily reversible e.g. electrolyte imbalance. DOESNT mean lifelong) Symptomatic – known brain disorder e.g. SOL / CP / head injury / metabolic / post infection etc Idiopathic epilepsy – No evident cause - presumed genetic. Incidence – 5% of people will have at least 1 epileptic seizure in their lifetime Prevalence in children = 0.5% with an epilepsy 1/3 of those with epilepsy will be misdiagnosed Over diagnosed = NOT epilepsy Underdiagnosed = missed Wrong epilepsy diagnosed à wrong Rx è Wrong prognosis & treatment given è Beware if FH of epilepsy – the relatives may be wrongly diagnosed = no FH! Types of seizures Generalised epileptic seizure = a seizures whose INITIAL semiology indicates, or is consistent with, more than minimal involvement of both cerebral hemispheres Generalised Tonic Clonic Seizures (GTCS) Sudden LOC, fall, tonic (limbs extended, back arched, resp ceases), clonic (jerking, micturition, salivation – should be less than 30mins), gradual regain of consciousness Tonic – increase in tone Myoclonic – sudden shock like contraction of muscles (single / repeated) Predominantly flexor/extensor, can be head drop or violent movements, idiopathic but common with mental handicap Tend to throw self backward Atonic – loss of postural tone, tend to fall backwards Absence – loss/impair of conscious, can have lip smacking etc Can be provoked by hyperventilation (90% if hypervent for 3mins) Idiopathic, often +ve FH, good prognosis Usually 4-10 yrs old. Last no more that 20 secs EEG (3 sec spike & wave), Typical = abrupt start & end Atypical = drift in & out (more common in learning diffs) Treat with valproate / ethosuximide Focal epileptic seizures = a seizure whose initial semiology indicates or is consistent with INITIAL activation of only one part of the brain NB: these can then spread to become 2o generalised Can be divided in to sensory (hallucinations) / motor (muscle) OR by lobe of brain involved Frontal – movement Temporal – emotion, memory, smell, taste & hearing Parietal – sensory Occipital – vision EEG interpretation If in all leads = generalised If in one or two leads = focal Odd = RHS, Evens = LHS If paroxysmal à spike / spike & wave If periodic à burst suppression If continuous à hypps arrhythmia If SSPE = large amplitude periodic slow wave ever 3.5-4s 3 Hz Spike & Wave = Absences High Amplitude spike in centro-temporal areas = Rolandic Periodic complexes in temporal region = Herpes simplex encephalitis High amplitude slow waves & multifocal spikes in chaotic pattern = Hypps Arrthmia = TS High amplitude slow wave in focal region = SOL Epilepsy syndromes: Characteristics e.g. Age, seizure types, EEG findings, Developmental problems 5 axis classification of epilepsies 1. Describe e.g. GTCS 2. Name type e.g. generalised 3. Syndrome e.g. idiopathic 4. Cause e.g. idiopathic, tuberous sclerosis etc 5. Impairment e.g. developmental delay Childhood Absences 5% of all epilepsies Onset 3-12y m:f = 1:3 Frequent brief (5-20secs) Developmentally normal Strong genetic predisposition Tend to improve in teens EEG – bilateral, synchronous & symmetrical spike & wave discharges at 3Hz Rx: valproate / ethosuxemide 30% will have some cognitive impairment Juvenile absence (JAE) Juvenile Myoclonic Onset 8-26y Usually familial Normal intelligence Present with GTCS (provoked by lack of sleep) or absences Then hx of early morning brief extensor myoclonic jerks (clumsy at breakfast) EEG – polyspike & wave complexes, generalised >3Hz discharges. Photosensitivity in 70-80% Rx: AVOID carbamazepine (can worsen). Usually life long treatment Severe myoclonic epilepsy of infancy (SMEI) – a.k.a. dravets Infantile Spasms Onset 3-8 months - bad prognosis - developmental regression Mixed flexor & extensor spasms, repetitive stereotypical movements (Salaam Attacks) - up to 100x/day in clusters of 15-30mins, more severe on waking Can be Cryptogenic (20% - with normal motor milestones, CT & neuro examination) or Symptomatic (have underlying cause) e.g. HIE, PVL, Congenital Infection, Inborn errors of metabolism or neurocutaneous syndromes (e.g. Tuberous Sclerosis) Usually cease spontaneously 2-3 yrs, can à later epilepsy EEG - (hypsarrythmia) Rx: vigabatrin, valproate, lamotragine, steroids (ACTH) West Syndrome Triad of : • Infantile spasms - in clusters, recovery at end of cluster • Developmental regression • Specific EEG – HYPSARRYHTHMIA = high volt disorganised & chaotic background, high volt asynchronous spike/polyspike waves, drop in voltage with fits Onset 4-6 months. Poor prognosis 5% mortality ½ of survivors have severe developmental delay, other ½ have persistent seizures Ohtahara syndrome – unremitting seizures within hours of birth Dravet syndrome – polymorphous myoclonic. Presents around 1 yr with febrile seizures Lennox-Gestaut Multiple seizure types, - slow spike & wave EEG in sleep Onsets 2-8 yrs Causes mental retardation, behavioural disturbance and poor social skills 30% have infantile spasms Poor prognosis Rx with Valproate EEG polyrhythmic background with high voltage irregular delta waves & irregular spike & waves Landau-Kleffner – Onset 3-8 (peak 5.5y). Expressive / receptive aphasia with normal hearing Regression of language/communications = expressive aphasia Aphasia can be permanent persisting EEG discharge (bitemporal) even between seizures Neuroimaging = NAD Rx valproate / clobazam / Improves with steroids. Early speech therapy is important Benign Epilepsy with centro-temporal Spikes (BECTS) Prev known as benign rolandic epilepsy Onset 3-13y (peak 9y) b>g Normal intelligence Usually FOCAL seizures within an hour of falling to sleep or just prior to waking During seizure – unable to speak, hypersalivation, feeling of suffocation, paraesthesia, motor involvement to one side of face. Can become generalised Lasts 1-2 minutes May become generalised Can (rarely) have daytime fits but always focal EEG – high voltage diphasic centro-temporal spikes. Can be unilateral/bilateral, activated by sleep/drowsiness. May be present in asymptomatic siblings Excellent prognosis – 90% seizure free by age 12 (improve at puberty) Treatment not usually needed as only occur at night. If need treatment try carbamazepine (beware can à sleep status) Pyridoxine (Vit b6) dependent seizures – NOT EPILEPSY Uusally present in newborn period High doses needed to control fits EEG normalises within 2-6 mins Non epileptic paroxysmal attacks Syncope & anoxic seizures (inc cardiac) Result of sudden decrease of O2 to brain e.g. vasovagal – often +ve FH, abdo discomfort prior to Sx. Often linked with sight of blood etc e.g. pallid syncope = reflex anoxic – bump to head / fright à asystole e.g. blue breath holding – prolonged expiratory apnoea e.g. long QT disorder – can à torsades du points e.g. simple faints e.g. obstructive syncope (sandifer’s syndrome / suffocation) Any of these can lead to anoxic seizures = Less than 60secs duration, Non-epileptic EEG, Can include tonic, convulsive jerks, eye deviation, incontinence and post ictal sleepiness Involuntary movements Rigors, jitters, shudders Paroxysmal dyskinesias Altering hemiplegia of infancy Behavioural & psychological Daydreams (imagining) pre-occupation (thinking about other current issues) Self gratification / masturbation Tics & stereotypies Pseudoseizures Usually 10-18y girls Lack of cyanosis No loss of sphincter control Normal pupil & planter responses Absence of injury Derangements of sleep Parasomnias (night terrors) – occur during sleep. Usually only 1 or 2 per night Nightmares Benign neonatal sleep myoclonus – usually in 1 limb Paroxysmal movement disorders Non epileptic myoclonus (inc benign neonatal sleep myoclonus) Dyskinesias e.g. Paroxsymal kinetogenic choreoathetosis Paroxysmal ataxias Cataplexy – sudden loss of tone linked to laughter / emotion, no loss of conscious Hyperekplexia – spasms induced by startle Migraine eqivalents Benign paroxysmal vertigo Cyclical vomiting Paroxysmal torticorlis Neonatal Convulsions Withdrawal, asphyxia, Febrile convulsions BMJ 2015;315:h4240 Epileptic seizures, even if recurrent, which are provoked by temporary disturbance ARE NOT epilepsy = as in febrile seizures Most are GTCS, can be asymmetrical. Brief suspension of awareness. Be sure to differentiate from rigors & delirium or reflex anoxic event. Recognised phenomenon of clusters of afebrile seizures in Rotavitus Gastroenteritis Known phenomenon of genetic epilepsy with febrile seizures plus (GEFS+). Febrile fits persist beyond 6 yrs. dravet's often starts I this way Febrile seizures (criteria) Incidence 2-5% Antipyretic use DOESNT reduce risk Usually occurring 6m – 6yrs (peak 18m) Assoc with fever (generally >38o) WITHOUT evidence of intracranial infection (OR other defined cause) Therefore if meningitis / cerebral palsy etc CANNOT be febrile cons Simple febrile seizures (70%) Generalised (no focal features) Short (< 10-15mins) – most will be <2 mins DONT recur within 24 hours OR same febrile illness Complex febrile seizures (30%) Focal features Last > 10 mins – if > 30 mins = febrile status Recur within 24 hours or same febrile illness Red flags for CNS infection: Irritable/lethargic Complex febrile Meningism Prolonged postictal beyond 1 hr Incomplete imms Other features B>G Black > White Family history. 1/5 if affected sibling. 1/3 if parents and sibling, high twin concordance Recurrence risk is 30-40%, 75% of these will be within 1 year of 1st fit Age <18m earlier = greater recurrence 50% if <1yr FH in 1st degree relative Duration of illness fever for <1hr before seizure Temp at time of seizure lower temp at time of seizure (4% if 0, 23% if 1, 32% with 2, 62% with 3, 76% if all 4) Risk of developing epilepsy 5x risk of developing epilepsy than those who have never had More likely if: Abnormal neuro / development prior to 1st seizure FH of afebrile seizures Complex febrile seizures (1% if 0, 2% if 1, 2 = 10%, if all 3 = 50%) Treatment: Benzos - only if prolonged febrile of very high risks No advantage to antipyretics Investigation of Seizures EEG – recording from 20 electrodes ONLY SOME EEG abnormalities are suggestive of epilepsy In subjects with definite epilepsy a single EEG will be normal in 40-50% of cases = lacks sensitivity Abnormal EEGs occur in 5% of NORMAL children therefore lacks specificity Rhythm / wave types Alpha – 8-12Hz, occipito-parietal region Beta - > 14Hz, frontal region Theta – 4-7Hz, seen in children, pathological in adults Delta – 1-3 Hz, pathological in ?adults? Burst Suppression – sign of ongoing anaesthesia Types Standard / routine = awake 50% abnormal in epilepsy With stimuli - e.g. hyperventilation / photostimulation Sleep - by deprivation / melatonin 80% abnormal in epilepsy Ambulatory – worn for 24 hours Videotelemetry – very expensive Should be used to SUPPORT a diagnosis of epilepsy (not to exclude it) Used to help determine seizure type à correct Rx & Prognosis CT & MRI Will only find cause in structural / physical problems e.g. SOL / HIE MRI is investigation of choice CT is better for calcification or blood Intracranial calcification Periventricular = TS / CMV Diffuse = Toxo Tram Line = Sturge Weber (meningeal) Supependymal = TS CT is more readily available in emergencies Imaging should be done if: <2yrs or adult at diagnosis Focal onset seizures Seizures continue despite 1st line Rx Other investigations BM during seizure No other mandatory ones But worth checking for Ca, Na, Mg & if syncope suspected then 12 lead ECG Can do functional imaging e.g. SPECT / PET Treatment of epileptic seizures AEDs will prevent seizure in 70-80% of cases Changing formulation is NOT recommended as can vary in bioavailability Benefits of Rx Reduction of restriction on lifestyle (e.g. driving / swimming etc) Improved school / work performance Reduced risk of status Starting AEDs Should only be initiated by a specialist WITH parental support Usually not started until after 2nd seizure (after 1st only if neuro deficit, EEG confirms dx, structural anomaly or risk of further seizure is unacceptable Side effects - Warn patient & parents CNS effects – can cause headaches, drowsy, irritable, hyperactive Carbemazepine à drowsy (can impair school), SLE type syndrome, dizziness & ataxia, Hyponatraemia in toxicity, ataxia, dizziness, blood dyscrasias Valproate à irritable & moody, behaviour disturbance, confusion, sleeps & increased Wt, Hepatotoxicity in children under 3 yrs (& those with metabolic / degenerative disorders). Treatment should be stopped if INR significantly raised. Also nausea, agitation, tremor, increased appetite, weight gain, hair loss, aggressive behaviour Vigabatrin - Permanent visual field loss (in upto 30% of patients) Lamotragine – rash, behavioural disturbance, irritable Phenytoin: dizziness, headache, tremor, gum hypertrophy, coarse face, hisuitism, peripheral neuropathy Paraldehyde – rectal irritation Topiramate – renal stones, sedation, anorexia, paraethesia Idiosyncratic reactions – not easily predicted e.g. rashes Teratogenic effects – background risk 2%, 1 AED à 5-6%, 2 AEDs à 10%. Valproate = biggest problem Drug interactions – with other AEDs / other drugs. E.g. COCP à reduced efficacy by many AEDs E.g. erythromycin à increased carbemazepine levels à toxicity Blood tests Most children DONT need any routine levels Use for ? Non compliance Suspected toxicity Adjusting phenytoin dose – small changes in dose can à large serum changes Management of drug interactions Specific conditions e.g. status, organ failure Stopping AEDs Should be done by a specialist Most childhood epilepsies will be grown out of Usually attempt to withdraw AEDs is after 2 years of seizure free But bear in mind age range for particular condition One drug at a time Over 2-3 months With plan in place for if seizures restart Relapse more likely if: learning difficulties, JME, symptomatic epilepsy, difficult to control If treatment not working ? Wrong diagnosis – may not be epilepsy ? Wrong choice of drug for type of seizures ? Inappropriate prescription – dose / frequency too low ? Medication interactions reducing efficacy ? Poor compliance ? Resistant epilepsy Preventative options (N= narrow, B = Broad) Agonists at inhibitory (GABA) synapses – valproate, vigabatrin Antagonists at excitation (glutamate) synapses – carbemazepine Reduced conduction in Ca2+ ion channels – ethosuximide, valproate Reduced conduction in Na ion channels – valproate, carbemazepine Older style drugs Carbemazepine = narrow spectrum of activity against FOCAL seizures (inc 2o generalised). MAY WORSEN 1o generalise seizures Not active against photosensitive seizures Valproate = broad spectrum against focal & general seizures Active against photosensitive seizures BUT is known to be teratogenic Can cause liver problems à increased ammonia (+N&V) Can also cause ataxia, rapid wt gain & decreased plts (with prolonged bleeding time) Can cause hyperactivity & behaviour problems Blood levels are only help to prove it is being taken - can be well above level without toxic sx Ethosuximide – narrow spectrum against typical absences – can à blood dyscrasia Phenytoin (N) à gingival hyperplasia, coarse face, hirsuitism, raised MCV & anaemia, low Plts, granulocytosis, osteomalacia, hypocalcaemia (affects vit D metabolism) - ataxia & peripheral neuropathy (if toxic) à nystagmus & dyskinesia Benzo’s (clobazam/clonazepam) (B) Phenobarbitone – can à hyperkinesias Newer drugs include vigabatrin (N) – against infantile spasms & seizures due to tuberous sclerosis Can à visual impairment (visual field defects in 10%) + increased appetite à increased wt in 12% Lamotragine (N) – withdraw if rash develops Gabapentin (N), Tiagabine (N), Topiramate (B) à anorexia & wt loss Levetiracetam = Keppra (B) Rescue Medication Seizures lasting > 30 minutes are thought to cause brain damage And seizures are harder to stop the longer they have been going Therefore aim to give rescue medication to stop seizures after 5-10 minutes to prevent it becoming a prolonged seizure Options include Diazepam – rectal should be 1st line Midazolam – buccal / nasal is more acceptable to families BUT unlicensed Paraldehyde - rectal Non AED treatment Ketogenic diet High fat, low carbs à high ketones in system à cross BBB à lowers fits Any deviation à rebound Need nutritional supplements Not very palatable Vagal nerve stimulator Pulse generator – continuous pulses – more firing = less fits Magnet increases pulses if moved past (STOPS pulses if held over) Use left vagus nerve Surgery Can be palliative (e.g. in lennox gestaux) or curative (e.g. remove tumour) Complications of Epilepsy Status Epilepticus 1 fit > 30 mins / repeated fits with no interictal recovery First aid for 1st 5 minutes Then medication to prevent prolonged seizure IV access – lorazepam 0.1 mg / kg PR - IV diazepam preparation 0.5mg/kg Buccal – 0.2mg/kg midazolam as buccal / nasal If continuing 10 minutes after medication rpt IV diazepam or give Paraldehyde 0.4mls/kg If no reponse à phenobarbitone à rapid sequence induction Ix BM, Gas, UE, Ca, Mg, FBC, Cult (if febrile), LFTs, AED levels, urine tox + organic acids, serum ammonia, lactate and aa’s Causes of status 50% idiopathic – 25% febrile, 25% epilepsy 25% Acute sx – infection, trauma, anoxia, metabolic disturbance, drug toxicity 25% Chronic sx – previous injury, malformations, progressive encephalopathy 3-6% mortality, 20% morbidity – increases if < 3yrs old Physical Injury Usually in children with existing earning difficulties NO evidence for injury in children with normal cognition before diagnosis of epilepsy Risk of premature death In subjects with epilepsy is 2-3x general ppn MOST deaths occur in children with syndromes / neuro-dev’ problems Some relate to underlying cause – e.g. SOL Some as result of seizure – e.g. fall / drowning Some due to psychiatric problems – depression à suicide Some due to Status Some due to SUDEP = sudden, witnessed/un-witnessed, non-traumatic, non-drowning death in patient with epilepsy, with/without evidence of seizure, excluding evidence of status, and post mortem doesn’t show toxicology / anatomical cause. Highest risk in young adults (18-35) Neurodevelopmental problems Idiopathic epilepsies DONT cause neurodevelopmental problems Symptomatic epilepsies often assoc with existing neurodev’ problems Epileptic encephalopathies à neurodevelopmental problems e.g. Lennox-Gastaut Syndrome & West Syndrome (infantile spasms) Can have temporary problems after seizures e.g. Todd’s paresis Psychiatric problems Higher incidence than general ppn for emotional / conduct disorders etc Schooling problems Can be due to missing school time (absences = missed instructions) Or due to SEs of medications e.g. drowsiness / hyperactivity Or due to bullying & stigmatisation due to diagnosis Safety considerations 3 most risky = water, heights & heat (cooking etc) Most can still be done with supervision NB: in epilepsy certain drugs are contraindicated / cautioned Mefloquine = contraindicated (risk of neuropsychotic symptoms) Chloroquine & ciprofloxacin à lower seizure threshold Neurofibromatosis NF1 = 1 / 2500 50% are new mutation 2/3 of people with NF1 are mildly affected and live normal lives 17q11-2 = tumour suppressor gene = AD Diagnosis – 2 or more of 6+ café au lait (>5mm if pre-pubertal, > 15mm if post-pubertal) can fade in adults 1 plexiform / 2+ neurofibromas Axillary / inguinal freckles Optic gliomas 2+ lisch nodules - Pigmented iris nodules – number increases with age Distinctive osseous lesions 1st degree family history Neurofibromas = benign pea-sized subcutaneous nodular tumours along peripheral nerves Rare in childhood, increase with age If in head/neck = plexiform = serious complications If bone involvement à pseudoarthritis + bowing of long bones + increased scoliosis Complications Optic gliomas – usually occur before 7yrs old. Can be bilateral. Rarely causes visual problems Problems with growth of tibia/skull around eye – usually occurs in infancy Scoliosis – can occur any time while growing General increased malignancy risk – approx. 10% lifetime risk esp phaechromocytoma Increased hydrocephalus & learning difficulties (aqueduct stenosis) Some learning difficulty in 1-2/3 e.g. DCD Increased renal artery stenosis + systemic HTN à vascular accidents Mx Genetic counselling & annual surveillance including vision and BP checks Tuberous Sclerosis Potato like hamartomas (tubers) in brain which calcifies (sclerosis) AD Neurocutaneous syndromes 70% = new mutations - 9q or 16p = ? tumour suppressor genes 1/20,000 Sx Ash leaf shapes depigmented macules Seen best with woods lamp in darkened room Shagreen patch = roughened skin over lumbar spine Facial angiofibromas (nasolabial folds, cheeks & chin) } Late childhood/ Periungual fibromas } early teens 80% develop epilepsy (usually by 5 yrs) Cognitive difficulties in 50% Infantile spasms, early onset intractable seziures & multiple cerebral tumours Also assoc with cardiac rhabdomyosarcomas à Fetal hydrops / failure Also assoc with polycycstic kidneys, renal & hepatic angiomyolipomas & retinal astrocytomas Diagnosis – 2 of • Skin: hypopigmented macule, ash leaf patches, adenoma sebaceum, shagreen patches Non traumatic ungual/periungual fibromas Teeth: enamel pits Eye: choroidal hamartomas, hypopigmented patches in iris, Retinal astrocytomas • • • • CNS: periventricular tubers, cerebral astrocytomas, sacrococcygeal chordomas • CVS: cardiac rhabdomyomas • Renal: Angiomyolipomas • Lungs: diffuse interstitial fibrosis • NB: developmental delay is common but not diagnostic Treatment Seziures – vigabatrin Behaviour therapy Laser treatments to facial angiofibromas (for cosmesis) Sturge Weber Syndrome Port wine stain + venous angioma of leptomeninges (OR glaucoma of eye) 8% of port wine stains (80% of ophthalmic trigeminal), 33% of bilateral PWSs Facial lesion doesn’t correlate to the intracranial angioma 75% à seizures (within 1st year & often resistant to anticonvulsants) 80% cognitive defect (30% profound). Degree of defect correlates to fits 50% hemiplegia (contralateral to angioma) Diagnosis Assess all with focal fits closely for PWS CT brain = “railroad track” calcification of cortex Management If intractable fits à functional hemispherectomy Laser of cosmesis Glaucoma surveillance Raised Intra-cranial pressure Cranial contents = 80% brain, 10% blood, 10% CSF CSF is actively secreted by choroid plexus & passively reabsorbed by arachnoid granulations Cerebral perfusion pressure = MAP – ICP (-CVP) CSF Production drops if cerebral blood flow drops Raised ICP à drop in cerebral blood flow à anoxia MAP & ICP increase with age ICP in neonate = < 3.5mmHg, < 7 in childhood, < 15 in adolescent / adult (1.36cm H20 = 1mmHg) Can be monitored by occipitofrontal circumference Sutures usually close at 18 months Causes of raised ICP Cranial abnormalities – primary craniosyntosis CSF / blood flow abnormality – extradural haemorrhage, subdural / subarach lesions, changes to CSF dynamics, benign intracranial HTN Parenchymal involvement – neoplasm, infection, head injury, HIE, Reye syndrome, inborn errors of metabolism, diabetic encephalopathy, hepatic coma Hydrocephalus Non communicating (proximal to 4th ventricle outlet) – aqueduct stenosis, chiari malformation, Dandy-walker syndrome, atresia or foramen of munroe, skull base abnormalities, mass effect from intracranial lesions, inflammatory ventriclitis Communicating – leptomeningeal irritation, carcinomatous meningitis Management – VA / VP shunt, endoscopic ventriculostomy Manifestations of raised ICP Impaired upgaze – setting sun eye – due to pressure over pre-tectal region due to supratentorial mass. Can also get retraction of eyelids Change in personality / sleep – irritable, lethargy, mood swings, decreased school performance, poor nocturnal sleep Diplopia – CN6 palsy Headache – worse in the am / straining / coughing Also – seizures, papilloedema, increased head circumference, full fontanelles, decreased sensation, CUSHINGS response (high BP, low HR) Brain Herniation Subfalcial herniation of cigulate gyrus à compression of anterior cerebral artery à infarct à UMN paralysis of contra-lateral leg Transtentorial herniation of uncus & parahippocampal gyrus - altered conscious due to pressure on diencephalon & mesencephalon with ipsilateral pupil dilatation fb fixation fb fixation of contra-lateral pupil, then CNIII palsy. Initial contra-lateral hemiplegia secondary to expanding lesion à progresses to include ipsilateral side à respiratory dysrhythmias secondary to brain stem pressure Cerebellar tonsil herniation through foramen magnum à progressive apnoea & quadriplegia Management – avoid hypovolaemia Head elevation 30 degrees Manage elevation and control temperature Decrease cerebral blood volume – hyperventilate to decrease PCO2 à vasoconstriction = 30 mins to act) Decrease brain & CSF volume – mannitol & furosemide (15 mins to act), synergistic used together. Acetazolamide (carbonic anhydrase inhibitor), steroids, shunt / tap Increase intracranial volume – if craniosyntosis IQ Average IQ = 100 (SD = 15) Mild learning disability = 50-69 Moderate = 35-49 Severe =20-34 Profound = < 20 } mild + moderate = } 5/1000 68% with known cause ] severe + profound = ] 3.8/1000 96% with known cause Assessment tools Griffiths – 0-8yrs – needs parental support. Timed test Bailey II – 0-42m Mild – mod LD – usually have no other problems. Some are just end of normal spectrum, some are environmental e.g. hypothyroid due to low I2 Severe LD – ¼ have chromosomal problem (80-90% = T21), then fragile X Disability Disorder – medically definable condition / disease Impairment – Loss or abnormality of psychological, physiological or anatomical structure / function Disability – any restriction / lack (resulting from an impairment) of ability to perform an activity in the manner or within the range considered normal for a child of that age Handicap – the impact of impairment / disability on the person’s pursuits or achievement of goals that are desired by him/her or expected of him/her by society. Disorder Spastic diplegia Impairment Increased muscle tone Profound Hearing loss due to Disability Abnormal gait & delayed motor milestones Impaired hearing & Handicap Inability to join in games / physical activities Inability to communicate sensorineural deafness Epilepsy NEW TERMS cochlear / neural pathways delayed speech with strangers Tendency to recurrent seizures Body structure / function Restriction in group activities participation May affect school attendance activities Developmental warning signs At any age Maternal concerns Regression of previously learnt skills 10 weeks Not smiling 6 months Persisting primitive reflexes Persistent squint Hand preference Little interest in toys / people / noises 10-12 months No sitting No double-syllable babble No pincer grip At 18 months Not walking independently Fewer than 6 words Persistent mouthing / drooling At 2 ½ years No 2-3 word sentences At 4 years Unintelligible speech Degenerative disorders Patterns of neurodegeneration White matter – spastic paresis + ataxia, loss of tendon reflexes, blindness + optic atrophy (normal retina) Grey matter – seizures, myoclonus, dementia, blindness + retinal change Raised ICP – tumour, hydrocephalus Epilepsy – esp. with poor control, non-convulsive status, Landau-Kleffner syndrome, epileptic encephalopathy Metabolic / Neurodegen Neonatal onset AA disorders, galactosaemia, MSUD Urea cycle errors Peroxisomal disorders – e.g. Zellwegers, neonatal adrenoleucodystrophy Mitochondrial – leighs Ketotic & non-ketotic hyperglycinaemia Sulphite oxidase deficiency Onset < 2yrs AA – PKU, homocystinuria Lysosomal Sphingolipidosis GM1 (B galactosidase def), GM2 (Hexosaminidase def) Gauchers – glucocerebrosidase def Niemann Pick – Sphingomyelinase def Metachromic Leucodystophy – arylsulphatase def Krabbe’s – galactosylceramidase def Mucopolysaccharidoses Mucolipidoses Glycoproteinoses Neuronal ceroid lipofuscinoses (aka Battens) Rare, AR neurodegenerative disorder most common group of neuro-degenerative disorders in children & teens Classified into infantile, late infantile, juvenile and adult (all AR except adult = AD) à accumulation of lipopigment in neurones Main clinical symptoms = progressive visual loss, dementia, motor decline, therapy resistant epilepsy à death Depending on which type of NCL will affect onset, sx, prognosis etc Battens = Juvenile = Most common Sx – start around 4-10yrs. Gradual onset of vision problems / myoclonic seizures Can be behavioural changes, learning regression, echolalia, clumsiness Other sx – poor growth, poor circulation, decreased body fat & muscle mass Infantile = more severe & earlier death (Life expectancy = 8-12 years post diagnosis) + many other forms & subforms Diagnosis based on: • • • § § Tripeptidly peptidase enzyme defect on dried blood spots, leucocytes & skin fibroblasts Gene mutation analysis (CNL2, 5, 6 & 8 genes) Electron microscopy for intra-lysosomal material (e.g. curvilinear bodies) Opthalmological findings (pigmentary retinal degeneration, optic nerve atrophy, enlarged Visual evoked potentials, large photic spikes on EEG MRI findings (generalised brain atrophy, hypo-intense thalami & periventricular hyperintensity that progresses to diffuse white matter hypersensitivity on T2 imaging Ix to exclude treatable causes e.g. Wilsons, hypothyroid, infection etc Rx - none specific available. Supportive management Mitochondrial disorders – Leighs, Alpers, Menkes Menkes – X-linked recessive Xq12-13 CU transport and metabolism error à low Cu & ceurolplasmin Progressive neurodegenative Symptoms begin in 1st few months inc hypotonia, hypothermia & generalised myoclonic seizures Cubby rosy cheeks Sparse poorly pigmented wirey, fragile hair Development of early dementia / severe mental retardation Optic atrophy Decreased serum Cu & ceruloplasmin Leigh Disease Mitochondrial DNA mutation à sub-acute necrotising encephalomyelitis 3m-2yrs Progressive deterioration – hypotonia + regression + nystagmus / opthalmoplegia + abnormal breathing Global developmental delay, ataxia, nystagmus Long tract signs & basal ganglia attenuation Increased CSF lactate Grey matter abnormalities on MRI Also assoc with tremor, increased tone and general seizure 4 different forms of disease Lesch-Nyhan X-linked Deficiency in hypoxanthine-guanine-phosphoribosyn-transferase Motor delay with limb rigidity, spasticity and chorea Self mutilation Increased uric acid levels Alexander’s disease – mutation in gene for glial fibrillary acidic protein (GFAP) Canavans – aspartocylase error à increased N-acetylaspartic acid BOTH cause hypotonia with megaencephaly & leucodystrophy Rett syndrome Genetic disorder - MECP2 on X chromosome. 95% de-novo mutation Mainly females affected, male fetus rarely survive to term (almost all surviving males have kleinfelters XXY) Apparent normal development of at least 6 months (usually to 18m) Then general decrease of function, loss of motor milestones with regression of speech Stereotypical small hands & specific hand movements & microcephally. Breath holding / hyperventilation. Often mistaken for autism Late stage à spacticity, dystonia, scoliosis, decreased cognitive function Inflammation / infection – HIV, SSPE (measles), ADEM, CJD Aids Encephalopathy Commonest neurodegeneration condition in children worldwide Due to opportunistic infection/HIV virus untreated Loss of milestones, microcephaly, dementia, spasticity, increased CSF protein (slightly decreased glucose), neuro-imaging à may be calcification of basal ganglia Poor prognosis SSPE (sub-acute sclerosing panencephalitis) Due to chronic persistent measles Usually due to virus in 1st 1-2 years of life Sx – within 6 yrs Subtle personality change, decreased IQ, behaviour change Myoclonic jerks, dementia, spasticity Die within 3 yrs CSF contains anti-measles Ab No treatment available Vascular e.g. repeated infarct due to sickle, Moya-Moya Endocrine – hypothyroid Toxic – lead poisoning, drug ingestion Nutrition – Thiamine/B12 deficiency, pellagra Psychological Pelizaeus-merzbacher Syndrome X linked dysmyelinating encephalopathy – defect in myelin sheath PLP1 gene Early hypotonia with evolving spacticity, head bobbing, nystagmus and stridor Adrenoleucodystrophy XR accumulation of LVCFA’s Onset 5-10yrs Decreased behaviour & school work Decreased co-ordination & gait à persistent vegetative state within 3 yrs Raised CSF protein & high signal in periventricular white matter Metachromic Leucodystrophy Arylsulphatase A deficiency = lysosomal storage disease 4 different presentations Infantile = presents before 4years, develops quickly with death within 5 years of diagnosis Others are Early Juvenile, Late Juvenile & Adult All forms involve progressive deterioration of motor & neurocognitive function Bone marrow transplants may help in ASYMPTOMATIC patients – too late if symptomatic Downs 1/1000 (1/100 if > 40y) Mostly non-dysjunction (75% maternal, 25% paternal) Recurrence risk = 2x ppn risk 3-4% are translocation (parent may be balanced translocation therefore asymptomatic à massive increased recurrence risk) 2-6% are mosaic = less severe CHD in 40-50% Atlanto-axial instability – warn parents of sx of cord compression Typical facies Brushfield spots – in iris Fine soft hair – can have alopecia Dry hyperkeratotic skin with vitiligo/mottling Hypotonia Increased infections, increased leukaemia, hypothyroid, low fertility in males, behavioural difficulties, initial poor growth (then overgrowth), pre-senile dementia Fragile X 1/1360 males (1/2000 females) Expansion in CGG triplet repeat on X Long face, increased HC, large jaw & ears, flat nose, abnormal fingerprints, macro-orchidism, low infantile tone, connective tissue dysplasia (joint laxity and velvety skin), aortic dilatation & mitral prolapse, recurrent OM, FTT in infancy, tonic-clonic/partial seizures Temporal spikes on EEG, variable intellect, language delay, social problems (similar to autism), attention and concentration difficulties Specific learning difficulties Dyslexia – reading Dysgraphia – writing Dyscalculia – maths – increased in fragile X, XO, PKU & ADHS Developmental co-ordination disorder = motor problems Differentials Muscular dystrophy CP Brain injury/tumour Hydrocephalus Metabolic Ataxia Polyneuropathy Seizure disorder Vestibular disease Tremors/involuntary movements ADHD Inattention Hyperactivity Impulsivity } } } in > 1 situation at <6y old impairing education / social function + secondary problems Poor self esteem Poor peer relationships / parental relationships Sleep/wake problems Dietary problems (won’t sit still to eat) b>g B mainly aggression, G mainly inattention estimated 54-98% heritability + environmental influence (social/parental) + CNS damage (if genetic/metabolic/insult) Comorbidities Low IQ (5-15 below peers) Specific learning difficulties Delayed language Co-ordination problems Conduct / oppositional defiant disorder Mood problems OCD Tourette’s ASD (autistic spec) Rx Behaviour modification School help Meds – methylphenidate/dexamphetamine = 80% success –if no effect after 3/52 then stop SE of methylphenidate – stomach/headaches, decreased appetite, sleep disturbance, raised BP, unhappy/withdrawal, growth suppression, rebound on dose ending, tics, marrow aplasia (rare) Can use atomoxetine (70% success) Also try diet changes & melatonin for sleep Communication disorders Attention & listening skills Symbolic understanding Comprehension Expressive speech Phonology Oro-motor skills Grammar/syntax Semantic Non-verbal communication Delay = slow to develop Disorder = abnormal development 5-7% have significant language difficulties – speech problems e.g. cleft lip/palate Autistic spectrum Impaired social interaction – abnormal eye contact, decreased affection, decreased sharing/social understanding Impaired communication Rigidity or thought (decreased imaginative play) Classical autism - 0.5/1000 Aspergers – 0.25/1000 Autistic spectrum – up to 6/1000 Increased incidence if – fragile X, tuberous sclerosis, PKU, NF1, Downs, Williams, Duchenne, West Syn, Hydrocephalus, severe sensory deficits, congenital infection, encephalitis, hypothyroid, fetal alcohol syn, neurometabolic probs, High functioning autism presents at > 3yrs, superficially normal language. “oddness” at school Aspergers Highly developed special interests Verbal IQ> written Clumsy Better social skills than autism Increased insight to thoughts & feelings Cognitive understanding of social rules Weak Child Differentials Limb girdle dystrophies Inflammatory (dermatomyositis) Myasthenia Peripheral neuropathy Non-organic Ix CK – raised in MD, inflammation, hypothyroid, carnitine metabolism ESR/CRP – inflammation Myositis Ab – ANA, Anti-Mi-2, Anti-Jo-1 increased in inflammation Nerve Conduction – demyelination à slowing EMG – low amplitude = muscle pathology Muscle biopsy Muscular Dystrophy Duchenne MD 1/3000 boys - Commonest disabling neuromuscular disorder X-linked recessive, Xp21 - female carriers asymptomatic. 1/3 are spontaneous mutation Dystrophin error < 3% of normal dystrophin Increased CK until significant loss of muscle, then decreases Replacement of muscle with fat cells à pseudohypertrophy Diagnostic criteria: (1) weakness with onset in the legs (2) hyperlordosis with wide-based gait (3) hypertrophy of weak muscles (4) progressive course over time (5) reduced muscle contractility on electrical stimulation in advanced stages of the disease (6) absence of bladder or bowel dysfunction, sensory disturbance, or febrile illness. Symptoms in 1st 5 yrs Delayed walking, frequent falls, waddling gait, difficulty climbing stairs Calf pseudohypertrophy (enlarged but weak) – later wasting Can develop cardiac fibrosis à failure / arrhythmia à death Respiratory & spinal muscle involvement à chest infections Smooth muscle involvement à constipation Diagnosis – Gowers sign +ve Increased serum CK (>1000 iU /l) ** Consider in any boy not walking by 18months Genetics / muscle biopsy for dystrophin staining – will be less than 5% of normal. & will show degenerating & regenerating muscle fibres Prognosis Unable to walk by 8-11yrs Death by 18-28yrs (resp infection) Rx – steroids reduce rate of progression. NIV can increase survival by resp support Becker MD X linked Milder form - Dystrophin levels 30-80% of normal Later onset – Sx from 10-15yrs Facioscapulohumeral MD AD 95% have presented by age 20y Initially in skeletal muscle of face, scapulae & upper arms Can progress to other areas of body, often asymmetrical Normal life expectancy but can be severe disability Limb Girdle Dystrophy AR, M=F Affects muscles of hips & shoulders = limb girdle (hip > shoulder) Mimics Duchenne Can have myoglobinuria & pain with elevated CK Usually symmetrical & slowly progresses Onset 10-30yrs – sooner onset = more severe Myotonic Dystrophy AD unstable trinucleotide repeat on Chr 19 (DMPK gene) – increased no of repeats = earlier onset Worsened by the cold Parents not always diagnosed as most effects are late childhood / early adulthood If familial, MOTHER is affected parent Mother may have myotonic handshake / frontal balding, myopathic facies, learning dificulies, ptosis, catatacts Sx Mild weakness in 1st few years Then progressive wasting of distal muscles (= unusual for muscular diseases) Slow relaxation of muscles (e.g. hand shake / toy grasp) Face (tenting mouth), Infants – weak, floppy, bulbar paresis, respiratory failure à ventilation + NG feeds Teens – weak to face, hands, feet, ptosis, drooping of mouth Also assoc with - cardiac conduction defects, cataracts, testicular atrophy, floppy infant, poor feeding, mild-mod learning difficulties, frontal balding, multiple endocrinopathies ½ die by 50yrs Ix – tendency for Low IgG Hypothyroidism is common (if treated improved learning difficulties) Patients will need ECG – high risk of conduction abnormalities à death Type II DM is common therefore monitor BMs / GTT Dx – DNA for CTG repeat / EMG NB: dangerous to give GA as high risk of post op respiratory failure Myasthenia Autoimmune disorder – circulating Ab to acetrycholine receptors More common in girls Gradual onset Destruction of Ach receptors on post synaptic membranes à fatigueability with repeated muscle activity Assoc with thymus abnormality Maternal Ab transmission à neonatal = transient Sx – ptosis, strabismus, difficulty chewing, loss of facial expression, arm weakness If congenital - Floppy neonate, weak suck & cry, ptosis & weak facial muscles If pre-pubertal – usually male. Sero –ve for Abs Ptosis/diplopia in one/both eyes Relapse/remitting course 20% complete remission Post pubertal – more commonly girls, sero +ve Generalised inc bulbar, dysarthria, dysphagia & crisis (resp) if not treated Ix – Tensilon Test (edrophonium = Ach-esterase inhibitor) Can be hypersensitive to test dose – therefore have O2 & atropine & monitoring to hand Dx – fluctuating weakness worse with fatigue Electromyography will show progressive decreased response Rx – acetylcholinesterase inhibitors e.g. neostigmine / pyridostigmine Thymectomy may help. Spinal muscular atrophy 1/10,000 – 1/20,000 5q12 AR Loss of anterior horn cells in cord & cranial nerve nuclei No impact on cognitive function Proximal & trunk muscles most affected, legs > arms, Bell shaped chest Diaphragm, face & eyes affected last Type I – Acute infantile = Werdnig Hoffman 1/20,000 = 45% of all SMA AR Present by 6m as floppy infant with failure of development Sx Poor fetal movements 30%, Muscle fasciculation – esp tongue Floppy infant 60% - lack of antigravity muscles Poor suck due to bulbar palsy, Never able to sit Absent deep tendon reflexes Death by 2 yrs Type II – Chronic Infantile = Most common form AR on Chr 5 Normal development until 6/12 old Onset approx 1 yr (6 – 18m), Deterioration slows / ceases after initial phase Sx - Never able to stand, tremor in fingers (? Fasciculations). Pseudo hypertrophy of gasroc mm Deterioration based on resp muscle involvement Usually die in teens / early middle age Type III – Chronic Juvenile Mild form – appears after 18m Onset at any age (usually as walking difficulty) May progress to inability to walk Life expectancy may be normal Type IV – Adult onset Typically mid 30s Normal life expectancy Peripheral neuropathy Hereditary Motor Sensory Neuropathy – Slow progressive muscle wasting Distal & symetriacl pattern AD/AR/XL e.g. Charcot-Marie-Tooth disease = HMSN1 = AD 17p11.2 70% of all hereditary neuropathy – often asymptomatic Delayed motor milestone Toe walking Foot deformity (pes cavus) Progressive atrophy of perineal nerve Weak dorsiflexion with foot drop and high stepping gait Thigh spared, wasted calf – inverted champagne bottle leg Deep tendon reflexes disappear later Then distal hand mm affected Nerve conduction = demyelination with decreased velocity Guillian-Barre Syndrome 2/100,000 Aka acute inflammatory demyelinating polyneuropathy of autoimmune origin Mainly affects motor nerves (occasionally sensory) Antibodies à destruction of myelin sheath Common preceding illnesses are campylobacter, EBV and Mycoplasma Pneumonia (usually 23 weeks before) Sx – rapidly progressive ascending flaccid paralysis – only asymmetrical in 9% of cases Severity may range from mild weakness to complete tetraplegia & ventilatory failure flaccid paralysis of legs à trunk à arms à face Paraesthesia, numbness, ascending in nature, lower limbs before upper Hypo / areflexia occurs early Absent Babinskis CN involvement = droop, diplopia, dysarthria, dysphagia in 50% can cause bulbar weakness & resp failure Peak of Sx @ 4/52 of onset 7-15% need ventilation support Ix – MONITOR FVC as indication of respiratory function CSF – 2x normal protein (normal = 0.1-0.4g/l), normal glucose & cells Decreased motor nerve conduction velocities = demyelination Recovery aided by i.v. immunoglobulin, can affect respiratory muscles Miller-Fisher Syndrome – external opthalmoplegia, ataxia & areflexia Polymyositis Viral infection – faeco-oral route Acute onset If enters CNS à destruction of motor neurones & flaccid paralysis – most commonly in spine à pain & walking difficulty. Raised CK, will respond to steroids Transverse Myelitis Inflamatory demyelination of spinal cord Usually post infection OR due to MS Sudden onset with rapid progression over days / hours Flacid weakness with extensor plantars & increased deep tendon reflexes Treatment – steroids / symptomatic support Prognosis - variable Occulogyric crisis Sx Initial restlessness, agitation, malaise THEN Dystonic reaction – sustained upward deviation of eyes, hyperextended neck with open mouth, tongue protrusion & ocular pain Usually due to haloperidol or chlorpromazine Rx with procyclidine CSF Oligoclonal bands – in 90% of MS cases, but also Sarcoid, SLE & Syphylis Kearns-Sayre syndrome Mitochondrial myopathy Onset before 20 years Involves muscles controlling eyelid movement & extra ocular mm à ptosis & opthalmoplegia Also bilateral pigmentary retinopathy & cardiac abnormalities (e.g. heart block) Some present with cerebellar ataxia, proximal muscle weakness, deafness, DM, GH deficiency, hypoparathyroid or other endocrinopathies Muscle involvement can begin unilaterally à progressive bilateral deficit Stroke 2.6 / 100,000 in white 3.1/100,000 in black Ischaemic – sudden onset hemiparesis/focal neuro in previously well child Risk factors CHD - aortic/complex lesions Acquired HD - endocarditis, cardiomyopathy Vasculitis – HPS, meningitis, HIV, Kawasaki Vasculopathy – e.g sturge weber Vasospasm Haem – DIC, sickle, increased coagulopathy Metabolic – homocysteinuria Trauma Haemorrhagic – structural anomalies of cerebral vessels / coagulation problems Risk factors Vascular lesions – fistulae, aneurysms, AV malformations Haem – VIII, IX, Sickle, low plts Lesional – tumour Hemiplegia Epilepsy – todds paresis Migraine – hemiplegic variant Stroke – ischaemic / haem Tumour – esp brain stem Trauma – extra/subdural Infection – focal encephalitis, abscesses Demyelination – acute disseminated encephalomyelitis (ADEM), MS Diabetes – acute hypo Metabolic – mitochondrial Cerebellar hypoplasia Developmental disorders – arise in fetal life (as opposed to atrophy = later) Hypoplasia Dandy-walker - agenesis of cerebellar vermis, 4th ventricle, cysts & hydrocephalus Joubert’s Syndrome – vermis agenesis, neonatal breathing disturbance, abnormal eye movements Smith-Lemli-Opitz syndrome – learning difficulties, low cholesterol Microcephaly, seizures Typical facies (ptosis, broad upturned nose, micrognathia) Syndactly of 2nd & 3rd toes Clenched hand Cryptochidism & hypospadias Fetal alcohol syndrome T13, T18 and Fragile X Progressive cerebellar Atrophy Pontocerebellar atrophy Carbohydrate deficient glycoprotein syndrome Spino-cerebellar degenerative condition Tay-sachs Menkes disease Retts PKU Nerve Injuries Mobius Syndrome Very rare – due to underdevelopment of nerves Congenital facial and abducens nerve palsy – usually bilateral (can spare lower face) Can à ectropion, epiphoria and keratopathy to eyes Convergent squint due to abducens palsy Abduction weakness uni/bilateral = usually complete Can involve 5th, 10th, 11th & 12th Nerves 3rd Nerve Palsy Ptosis (partial / complex) Divergent Squint (down & out due to unopposed action of LR & SO) If internal branch affected = + pupil dilatation Congenital – developmental / birth trauma Acquired – SOL, Aneurysm, Trauma, Post viral syndrome, Migraine 4th Nerve Supplies SO Enters orbit via Superior orbital fissure Runs in lateral wall of cavernouis sinus Spinal Cord injury Hemisection = Brown’s Sequard Loss of Ipsilateral paralysis, proprio, touch & vibration sensation & contralateral pain & temperature Anterior cord injury Loss of motor Retain proprio, touch & vibration Specific named nerves Radial Nerve – wrist drop & wrist & finger extensors Median nerve à sensory to radial 2/3 of hand + short finger flexors, abductors, opponens of thumb & lumbricals to index & middle finger Ulnar nerve à sensory to ulnar border of hand & rest of small muscles of the hand Sciatic Nerve - L4-S3 Injury à Weak knee flexors (not extensors) Lateral & posterior lower leg decreased sensation Weak plantar flexion (+ dorsiflexion if severe) Absent ankle jerk Reflexes Biceps C5-6 Supinator Triceps C7-8 Knee Ankle C5-6 L3-4 S1-2