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 à 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