Chapter 86 – Neonatal Neurology


Neonatal seizures

·         Often caused by serious disturbances

·         Causes decr brain glucose, incr lactate, excitatory AAs, low phosphocreatine

·         Common seizure types:

o        Subtle – eye deviation/blinking/staring, mouth/tongue movts, apnea, pedaling, tonic posturing

o        Tonic (focal or gen) – more in IVH

o        Clonic (multifocal or focal) – more in focal infarct or trauma, diff from jitteriness

o        Myoclonic (focal, multifocal, or gen) – rare, diff from benign neonatal sleep myoclonus

·         Poor concordance of seizure-like movements and EEG

·         Seizures < 3 days of life:

o        HIE, IVH, SAH, hypoglycemia, early hypocalcemia, drug withdrawal

·         Seizures > 3 days of life:

o        Late hypocalcemia, bacterial/viral meningitis

·         Genetic defects usually cause seizures later except benign familial neonatal epilepsy

·         Therapy for glucose, calcium, magnesium, pyridoxine

·         Pyridoxine 50-100mg IV acutely, then trial of 50-100mg qday for 2 weeks


Hypoxic ischemic encephalopathy (terms)

·         Reduced oxygen to brain, build up lactate, free radicals, excitotoxic AAs

·         Acute total asphyxia – injury to thalami, basal ganglia, brainstem nuclei

·         Prolonged partial asphyxia – cerebral cortical and subcortical injury

·         Clinical features:

o        Initial – decr LOC, periodic breathing, hypotonia, seizures

o        12-24h – apparent alertness, worse seizures, apnea

o        24-72h – LOC deteriorates, brainstem abnormalities (maximum ICP)

o        >72h – if survive, stupor, abnorm tone, brainstem dysfunction (suck, swallow)

·         Neuropath correlations:

o        Selective neuronal necrosis

§         Cerebral / cerebellar cortex, thalamus, brainstem nuclei

§         Coma, seizures, hypotonia, abnorm oculomotor/suck/swallow

o        Status marmoratus

§         Thalamus, basal ganglia

§         Term > Preterm

o        Parasagittal

§         Cerebral cortex, subcortical white matter

§         Proximal limb weakness, arms>legs

o        Periventricular leukomalacia

§         Periventricular white matter

§         Prems, lower limb weakness

o        Focal/multifocal

§         Unilateral or bilateral cortex and white matter

§         Variable hemiparesis/quadriparesis

§         Stereotyped, nonhabituating reflex responses

·         Classification of severity:

o        Mild HIE

§         Incr irritability, exaggerated Moro and tendon reflexes, sympathetic overactivity

§         Recovery by 2 days, no longterm sequelae

o        Moderate HIE

§         Lethargy, hypotonia, decr reflexes, seizures

§         20-40% risk abnormal outcome

o        Severe HIE

§         Coma, flaccid tone, brainstem/autonomic dysfunction, seizures, incr ICP

§         Morbidity or severe morbidity

·         EEG is important for prognosis – if normal at 1 wk, favorable outcome

·         Evoked potentials – VEPs for PVL, ABRs for brainstem injury

·         Metabolics - Hypogly, hypoCa, hypoNa (SIADH), lactic acidosis

·         Neuroimaging

o        CT at 3-5 days shows maximal severity of injury

o        MRI more precise, also head U/S useful

·         Management

o        Best management is prevention – monitoring, C/S if fetal distress

o        Prevent further injury – manage ventilation, perfusion, glucose, seizures, organs

o        Ventilation – prevent hypoxemia, but not overcorrection causing lung injury

o        Cerebral blood flow is pressure-passive to systemic BP – prevent hypotension

o        Prevent hypertension causing germinal matrix hemorrhages

o        Hyperviscosity from polycythemia also impairs perfusion (partial exchange transfusion)

o        SIADH causing hypoosmolality, hyponatremia ΰ cerebral edema, seizures

o        Elevated ICP at 36-72h correlates with extensive hypodensities on CT

o        Treatment of ICP controversial

·         Prognostic factors:

o        Severity and duration of encephalopathy – most predictive

o        Seizures

o        Brain edema

o        EEG – isoelectric, suppressed bkgrd, burst-suppression

o        CT, U/S, MRI

o        Antenatal factors – low 10 minute Apgar scores

·         Severe HIE results in microcephaly, MR, seizures, spastic quad


Hemorrhagic and hypoxic-ischemic brain injury in preterms

·         IVH in 20% prems with BW <1500g, occurs day 1 (50%) to day 4 (90%)

·         80% germinal matrix hemorrhages extend into ventricles

·         “HIE” in prems result in PVL – spastic diplegia, quadriplegia, visual impairment

·         U/S is test of choice for IVH at day 3-4 in babies born <32wks GA

·         CT/MRI better for epidural, subdural, subarachnoid, intracerebral, posterior fossa bleeds

·         Clinical presentation variable, from asymptomatic to

o        Catastrophic deterioration, coma, apnea, tonic seizures, brainstem disturbances

o        Metabolic acidosis, hypotension, bradycaria, abnorm glucose/water homeostasis

·         Bloody/xanthochromic CSF

·         CT difficult in prems due to normal low attenuation of brain, MRI more helpful

·         Management:

o        Prevent bleed extension and hypoxic injury

o        Severe IVH can cause hypovolemia

o        Serial U/S and head circumference – hydrocephalus

§         Caused by arachnoiditis and/or aqueductal stenosis

o        50% self-resolve within 4 weeks, 50% require shunting, osmotic agents, diamox/lasix

·         Prognosis:

o        No significant morbidity if mild

o        Severe results in death or posthemorhagic hydrocephalus


Intraventricular hemorrhage (term)

·         Also result of hypoxia or trauma, but more likely trauma and increased venous pressure

·         Site of origin variable – germinal matrix, choroids plexus, vascular malform, tumours, hemorrhagic venous infarction of the thalamus

·         Prognosis worse in terms, longterm sequelae in >50% due to parenchymal damage


Neonatal CNS infections

·         Neonatal meningitis

o        Prems > terms

o        Early onset (first few days)

§         GBS, E.coli, Listeria monocytogenes

o        Late onset (after several days)

§         Staph, Pseudomonas

o        Risk includes maternal genital or urinary tract infection weeks before delivery

o        20-30% sepsis is complicated by meningitis – early LP

o        Management

§         Maternal IV ampicillin during labour if maternal GBS+

§         Empiric IV ampicillin + gentamycin/cefotaxime to neonate

§         Treat neonate min 21 days, 2 weeks after clear repeat LP

§         Repeat LP 48h after stopping antibiotics

§         Restrict fluids to 30-40ml/kg/d due to high risk of SIADH

§         Treat seizures with phenobarbital or phenytoin

§         Serial HC and HUS to R/O ventriculitis, hydrocephalus, dural effusion

o        Cerebral abscess rare (Citrobacter, Gram negative)

o        Mortality 20-30%, esp in gram-neg infections

o        Permanent neuro sequelae in 30-50% (hydrocephalus, CP, seizures, intellectual deficits, deaf)

·         Viral and parasitic infections (TORCH infections)

o        Congenital rubella

§         Incidence decreased with rubella immunization

§         Infection before 20wk GA

§         SGA, jaundice, HSM, petechial rash, cong heart disease, cataract, deaf, microcephaly, bony lesions, low PLT

§         Highly infectious – shed virus for years

§         Dx – throat/urine viral culture, plasma rubella IgM

§         Periventricular calcifications, subependymal cysts, PVL

§         Progressive hearing loss, behavioral/emotional prob, growth failure, DM

o        Congenital CMV infection

§         Most common infection, most asymptomatic

§         <10% - HSM, jaundice, petechiae, microcephaly, PV calcifications, chorioretinitis, blind, 20-30% mortality, severe long term neuro sequelae

§         Dx – throat/urine viral culture, serum CMV IgM

§         Tx – gangciclovir x3mo suggested (but already damaged)

o        Congenital HSV infection

§         Acquired from vaginal birth from mother with HSV lesions

§         Infection of oral, cutaneous, ophthalmic, CNS, disseminated (HSM, renal failure)

§         Dx – intranuclear inclusions in vesicular fluid, CSF, conjunctival scraping, throat/urine/stool cultures, CSF PCR

§         MRI/CT, incl DWI to delineate extent of injury

§         Tx – Acyclovir 30mg/kg/d x14d (not as effective as postnatally acquired infection)

o        Congenital toxoplasmosis

§         Acquired transplacentally

§         Affects eyes and CNS – necrosis/calcification of brain, hydrocephalus, cataracts, microphthalmia

§         Also affects liver, bone marrow, lungs, muscles, myocardium

§         Dx – Toxo IgM often negative, trophozoites in CSF

§         Tx – spiramycin, pyrimethamine, sulfadiazine + folinic acid  (mother+baby) x1yr

§         Corticosteroids if severe infection

§         1/3 are symptomatic, of those 25% mortality, others significant neuro sequelae

§         If asymptomatic, good prognosis

o        Congenital HIV infection

§         Transmission in utero, in L&D, or breastfeeding

§         Start asymptomatic, then opportunistic infections (CMV, Pneumocystis)

§         Dementia, cerebral atrophy, acquired microcephaly

§         Reduce risk with prenatal, perinatal, postnatal zidovudine

§         Elective C/S and avoid breastfeeding



Mechanical trauma

·         Intracranial hemorrhage

o        Subarachnoid, epidural, subdural, intracerebellar, less common than IVH

o        Usually due to birth trauma

o        CT for diagnosis

o        Subdural – if large, may require drainage

o        Subarachnoid – if isolated, normal outcome in 90%

o        Epidural – increased ICP, unilat fixed dilated pupil, seizures, immediate drainage

·         Extracranial hemorrhage

o        Caput seccedaneum – superficial bleeding between skin and epicranial aponeurosis

§         Vertex, crosses suture lines, resolves in days

o        Subgaleal hemorrhage – between aponeurosis and periosteum of skull

§         Entire scalp, crosses suture lines, marked blood loss, resolves in 2-3wks

o        Cephalohematoma – between periosteum and bone

§         Unilateral parietal, does not cross sutures, may calcify, resolves weeks-months

·         Skull fractures

o        Linear – usually parietal

o        Depressed – “ping pong fracture”

o        Occipital diastasis – traumatic separation of squamous and lateral parts of occipital bones

§         Not a fracture, from breech delivery

§         Assoc w/ post fossa subdural hx, cerebellar contusion, brainstem compression

o        CT scan to find linear fracture under cephalohematoma and brain under ping pong fracture

o        Treatment only if fracture affects underlying brain

o        Leptomeningeal cyst

§         Rare complication of skull fracture

§         Transilluminates, widening bony defect

·         Spinal cord injury

o        Uncommon, from excessive traction in delivery

o        Breech delivery (75%) – lower cervical, upper thoracic

o        Vertex delivery – upper cervical, mid cervical (e.g., forceps rotation)

o        Lower cervical / thoracic injury – vascular occlusion from UA cath or air emboli

o        Symptoms reflect level

o        C/S minimizes injury, except in utero vertebral artery occlusion

o        U/S, radiology, MRI to delineate lesion – R/O surgically correctable spinal dysraphism or extramedullar compression

·         PNS injury

o        Facial paralysis

§         From compression of facial nerve on sacral promontory

§         DDx congenital aplasia of depressor angularis muscle

§         Supportive, resolves in weeks to months

o        Brachial plexus injury

§         0.5-2.6 per 1000 live term births

§         usually upper roots of brachial plexus involved (Erb’s palsy)

·         loss of shoulder abduction, external rotation

·         loss of wrist/finger extension

·         absent biceps reflex, impaired abduction phase of Moro

§         lower roots rarely involved (Klumpke’s palsy)

·         intrinsic hand muscle involvement, absent grasp reflex

·         Horner’s syndrome in 1/3

§         5% involve diaphragmatic paralysis from injury of C3-5

·         check with fluoroscopy or U/S

§         assoc w/ Horner’s syndrome, fractured clavicle/humerus, subluxed shoulder/C-spine, cervical cord injury, facial palsy

§         Dx - by physical exam and EMG denervation. Screen for fractures

§         Tx – Immobilize on upper abdomen 7-10 days, then passive ROM exercises

§         Improvement at 2 weeks is favorable sign

§         88% recover by 4 mo, 92% by 12 months

§         Surgical reconstruction of plexus if no improvement at 4 months


Effects of drugs and toxins


·         Maternal alcohol abuse – growth retardation and intellectual deficits

·         Anticonvulsants – cong heart disease, cleft lip/palate

·         VPA – 5% risk of neural tube defects in first trimester

·         Fetal hydantoin syndrome – phenytoin, barbiturates, alcohol, trimethadione, valproate

o        Growth retardation, dev delay, dysmorphism, distal limb abnormalities

·         Heroin – microcephaly in 40%

·         Intracranial hemorrhage

o        Reduced vitK-dep factors (II, VII, IX, X)

o        Phenytoin, barbiturates, primidone

o        Prolonged INR or PTT

o        Treat with IV vitK at birth,

o        FFP if abnormal clotting, exchange transfusion if hemorrhagic disease

·         Passive addition and withdrawal syndrome

o        60-90% newborns of neuroactive drug-using mothers

o        Timing depends on drug half-life

§         Day 1 – heroin, alcohol, short-acting barbiturates, diazepam, TCAs, hydroxyzine, propoxyphene, pentazocine

§         Day 2-3 – methadone, cocaine

§         Day 7 – long-acting barbiturates

§         Day 21 – chlordiazepoxide

o        Symptoms similar for all withdrawal

§         Jitteriness, irritability, disturbed sleep-wake, shrill cry, frantic suck

§         GI disturbance (poor feeding, vomit, diarrhea)

§         Sneezing, tachypnea, excessive sweating

§         Fever and seizures uncommon (must R/O sepsis or other disorder)

o        Duration of symptoms

§         Weeks – long-acting barbiturates, hydroxyzine

§         Months – heroin

o        Supportive management, unless severe

§         Tincture of opium (0.4mg/mL morphine equivalent)

·         0.1mL/kg q3-4h, incr by 0.05-0.1mL to 0.2-0.5mL/kg

§         Paregoric 0.8-2mL/kg/d divided in 6-8 doses

·         contains camphor, not to be used in prems

§         Chlorpromazine 2-3mg/kg/d divided qid

·         Can cause EPS and increase seizures

§         Phenobarbital, diazepam control neurological symptoms only (not GI), and can increase drowsiness and feeding difficulties