Review – Kaplan Pediatrics: Neurology

CENTRAL NERVOUS SYSTEM (CNS) ANOMALIES

 

Neural Tube Defects

• Elevated alpha-fetoprotein is a

 

Spina bifida occulta

• Midline defect of vertebral bodies without protrusion of neural tissue; occasion- ally associated with other anomalies

•      Most asymptomatic and of no clinical consequence

• May have overlying midline lumbosacral defect (patch of hair, lipoma, dermal sinus)

 

Tethered cord

•      Ropelike filum terminale persists and anchors the conus below L2

• Abnormal tension¾asymmetric lower extremity growth, deformities, bladder dys- function, progressive scoliosis, diffuse pain, motor delay
• Most associated with a midline skin lesion

•      MRI needed for precise anatomy

• Surgical transection

 

Meningocele

• Meninges herniate through defect in posterior vertebral arches
• Fluctuant midline mass well covered with skin; may transilluminate
• Must determine extent of neural involvement with MRI
• CT scan of head for possible hydrocephalus
• Surgery

 

Myelomeningocele

The pediatrician is called to the delivery room because an infant is born with a defect in the lumbosacral area.

 

• Strong evidence that maternal periconceptional use of folate reduces risk by half
• May occur anywhere along the neuraxis, but most are lumbosacral

•      Low sacral lesions¾bowel and bladder incontinence and perineal anesthesia without motor impairment

 

 

 

 

Note

Almost every child with a sacral or lower lumbar spine lesion will achieve some form of functional ambulation, and half of those with higher spine defects will have some degree of hip flexor and hip adductor movement.

TheFetus.net

 

Figure 21-1. Arnold-Chiari Malformation, a Defect of the Hindbrain Usually Accompanied by Myelomeningocele

 

• Midlumbar lesion¾saclike cystic structure covered by thin, partially epithelized tissue
• Flaccid paralysis below the level of the lesion is most common; no deep tendon reflexes (DTRs), no response to touch and pain

–     Urinary dribbling, relaxed anal sphincter

• 80% associated with hydrocephalus; type II Chiari malformation¾may have symptoms of hindbrain dysfunction (feeding difficulty, choking, stridor, apnea, vocal cord paralysis, upper extremity spasticity)
• Evaluation and treatment
• Must evaluate for other anomalies prior to surgery
• Evaluate renal function

–     Head CT scan for possible hydrocephalus

• Treatment¾ventriculoperitoneal shunt and correction of defect

 

 

Hydrocephalus

A 2-month-old infant is noted to have a head circumference greater than the 95th percentile.

 

• Definition¾impaired circulation and absorption of CSF or, rarely, from increased CSF production from a choroid plexus papilloma
• Types
  • Obstructive (noncommunicative) versus nonobstructive (communicative) from obliteration of subarachnoid cisterns or malfunction of arachnoid villi
    • Obstructive¾most are abnormalities of the cerebral aqueduct (stenosis or gliosis; congenital, intrauterine infection, mumps, hemorrhage) or lesions near the fourth ventricle (brain tumor, Chiari malformation, Dandy-Walker malformation)
  • Nonobstructive¾occurs mostly with subarachnoid hemorrhage; also with pneumococcal or TB meningitis or leukemic infiltrates
• Clinical presentation¾depends on rate of rise of intracranial pressure
  • Infants:

°      Increased head circumference

• Bulging anterior fontanel
• Distended scalp veins
• Broad forehead

°      “Setting sun” sign

• Increased DTRs
• Spasticity, clonus

• Older child (subtler symptoms)
  • Irritability
  • Lethargy
  • Poor appetite
  • Vomiting

°      Headache

• Papilledema
• Sixth-nerve palsy

• Treatment for all types of hydrocephalus¾shunting

 

Dandy-Walker malformation

•      Cystic expansion of fourth ventricle due to absence of roof

• Associated agenesis of posterior cerebellar vermis and corpus callosum
• Presents with increasing head size and prominent occiput, long-tract signs, cerebellar ataxia, and delayed motor development, Å transillumination

 

 

 

TheFetus.net

 

Figure 21-2. Dandy Walker Malformation, the Result of Agenesis or Hypoplasia of the Cerebellar Vermis, Cystic Dilatation of the Fourth Ventricle, and Enlargement of the Posterior Fossa

 

 

SEIZURES

Seizures are triggered recurrently from within the brain versus somatic disorders that may trigger a seizure from outside the brain. Epilepsy is present when at least 2 unprovoked seizures occur >24 hours apart.

 

Febrile seizures

An 18-month-old child is brought to the emergency center after having a generalized tonic-clonic seizure that lasted approximately 5 min. The parents say that the child had been previously well but developed cold symptoms earlier today with a temperature of 39°C (102°F).

 

• Occurs between age 6 months to 5 years; incidence peaks at age 14–18 months and may reoccur with fever
• Usually positive family history
• Temperature usually increases rapidly to >39°C (102°F)

•      Typical: generalized tonic-clonic seizures, <10–15 minutes; brief postictal period

• Atypical: >15 minutes, more than one in a day, and focal findings

 

 

• Simple febrile seizure has no increased risk of epilepsy¾risk for febrile seizures is increased with atypical seizure, family history of epilepsy, initial seizure before age 6 months, abnormal development, or preexisting neurologic disorder
  • Workup/Evaluation
    • Must determine cause of fever, must not look like meningitis

°      No routine labs, no EEG, no neuroimaging

-Treatment¾control fever

 

Partial Seizures

Simple

• Asynchronous tonic or clonic movements; most of the face, neck, and extremi- ties; average duration 10–20 seconds
• Some have an aura and may verbalize during the attack; no postictal period

•      EEG ¾spike and sharp waves or multifocal spikes

• Treatment¾phenytoin and other anticonvulsants

 

Complex seizures

• Impaired consciousness at some point, may be very brief; one-third with aura (always indicates focal onset)
• Automatisms common after loss of consciousness (lip-smacking, chewing, swal- lowing, increased salivation)
• Interictal EEG¾anterior temporal lobe shows sharp waves or focal spikes
• MRI¾many will show abnormalities in temporal lobe (sclerosis, hamartoma, cyst, infarction, arteriovenous malformation [AVM], glioma)
• Treatment¾carbamazepine (drug of choice) and other add-ons

 

Generalized Seizures

Absence (petit mal)

•      Sudden cessation of motor activity or speech with blank stare and flickering eyes

• More in girls; uncommon <5 years of age
• No aura; usually <30 seconds; no postictal period

•      EEG ¾3/second spike and generalized wave discharge

• Treatment¾ethosuximide (drug of choice), valproic acid (second line)

 

Tonic-clonic seizures

• May have aura (focal onset; may indicate site of pathology); loss of consciousness, eyes roll back, tonic contraction, apnea
• Then clonic rhythmic contractions alternating with relaxation of all muscle groups
• Tongue-biting, loss of bladder control
• Semicomatose for up to 2 hours afterward with vomiting and bilateral frontal head- ache
• Treatment—valproic acid, phenobarbital, phenytoin, carbamazepine, and other add-ons

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Note

Benign Myoclonus of Infancy

• Often confused with myoclonic seizures
• Clusters confined to the neck, trunk, and extremities
• EEG normal
• Good prognosis
• Goes away after 2 years; no treatment

Myoclonic Seizures

• Repetitive seizures—brief, symmetric muscle contraction and loss of body tone with falling forward
• Five types, with variable severity, morbidity, and prognosis
• Treatment—valproic acid and others

 

Infantile Spasms

• Symmetric contractions of neck, trunk, and extremities (with extension episodes as well)
• Pathophysiology—increased corticotropin-releasing hormone (CRH): neuronal hyperexcitability
• Begin typically at 4–8 months of age
• Types
  • Cryptogenic—infant is normal prior to seizure with normal neurologic exam- ination development; good prognosis
  • Symptomatic—disease present prior to seizure (e.g., tuberous sclerosis); poor control and mental retardation
• EEG—hypsarrhythmia (asynchronous, chaotic bilateral spike-and-wave pattern)
• Treatment

–     Adrenocorticotropic hormone (ACTH); drug of choice

• Prednisone and add-on of other anticonvulsants if no response

 

Neonatal Seizures

• Because of immaturity of CNS, tend to have subtle seizures; therefore, they are difficult to recognize

• Etiology

–     Hypoxic ischemic encephalopathy most common; seizure usually present within 12–24 hours after birth

• CNS infection
• CNS hemorrhage
• Structural abnormalities
• Blood chemistry abnormalities
• Inborn errors of metabolism

–     Drug withdrawal

• Evaluation:
  • CBC; platelets
  • Electrolytes, calcium, magnesium, phosphorus; glucose
  • Lumbar puncture to exclude meningitis or bleed
  • CT scan in term, ultrasound in preterm to diagnose bleed
  • Blood and urine culture may be indicated (+CSF)
  • Consider newborn screen for inborn errors of metabolism, if abnormal results suggestive or no diagnosis
  • Treatment—lorazepam, phenobarbitol

 

 

Table 21-1. Neonatal Seizures

Cause	Presentation	Associations
Hypoxic ischemic encephalopathy	12–24 hours	Term; cerebral palsy
Intraventricular hemorrhage	1–7 days	Preterm
Metabolic	Variable	IODM (infant of diabetic mother), inborn errors of metabolism, DiGeorge syndrome
Infection	Variable	TORCH, maternal fever, sepsis/ meningitis

 

 

NEUROCUTANEOUS SYNDROMES

A 6-year-old presents to the pediatrician for a routine evaluation. The child is noted to have 10 café-au-lait lesions as well as axillary freckling.

 

Neurofibromatosis (NF; von Recklinghausen Disease)

 

 

NF-1

• Autosomal dominant; but most with new mutation
• Every organ can be affected; features present from birth but complications may be delayed into adulthood
• Diagnosis—a good history and physical examination are needed to make the
  • Two of the following are needed:

° At least 5 café-au-lait spots >5 mm prepubertal or at least 6 café-au-lait spots

>15 mm postpubertal

° Axillary/inguinal freckling

° >2 iris Lisch nodules (seen on slit lamp only)

° >2 neurofibromas or one plexiform neurofibroma

° Osseous lesions, splenoid dysplasia or cortical thinning of long-bones (LE)

° Optic gliomas

• Complications
  • CNS:

° Low-grade gliomas (optic), hamartomas

° Malignant neoplasms (astrocytoma, neurofibrosarcoma, and others)

° Transient ischemic attack, hemiparesis, hemorrhage

° Complex partial or generalized seizures

° Cognitive defects, learning disabilities, attention deficit, speech abnormali- ties, psychiatric disturbances

 

 

–      Renovascular hypertension or pheochromocytoma

• Increased incidence of leukemia, rhabdomyosarcoma, Wilms tumor
  • Treatment
    • Genetic counseling
    • Early detection of treatable conditions
    • Annual ophthalmologic examination
    • Examine family members

 

 

NF-2

 

• Presentation
• Primary feature—bilateral acoustic neuromas
• Hearing loss
• Facial weakness
• Headache
• Unsteady gait
• Skin findings much less common (glioma, meningioma, schwannoma)
• CNS tumors common
• Treatment
  • Developmental and cognitive evaluation and diagnosis
  • Prevent pathological fractures if LE cortical thinning present

 

 

Tuberous Sclerosis

A 1-month-old infant presents with infantile spasms and has a hypsarrhythmic EEG pattern.

• Autosomal dominant; half with new mutations
• Wide range of manifestations within same family
• The younger the patient, the higher the likelihood of mental retardation
• Hallmark is CNS tubers found in convolutions of cerebral hemispheres; undergo calcification and project into ventricular cavity, causing obstruction of CSF flow and
• Clinical presentation

• Infancy—with infantile spasms and characteristic skin lesions

° Ash-leaf macule—hypopigmented; increased with Wood UV lamp

° CT scan shows calcified tubers (but may not see till 3–4 years of age)

• Childhood—generalized seizures and skin lesions

° Sebaceous adenoma—red or clear nodules on nose and cheeks

° Shagreen patch—rough, raised lesion with orange-peel consistency; most in lumbosacral area (midline)

• Diagnosis—clinical: characteristic skin lesions and seizure disorder
• Treatment—seizure control

 

 

 

• Complications
  • Retinal lesions—either mulberry tumor from optic nerve head or phakomas (round, flat, gray lesions in area of disc)–visual disturbances
  • Brain tumors much less common (but may see malignant astrocytoma)
  • Half have rhabdomyoma of the heart (can detect in fetus with echocardio- gram); most spontaneously regress over first 2 years

–     Renal lesion in most—either hamartoma or polycystic kidneys

• Pulmonary—cystic or fibrous changes

 

Sturge-Weber Syndrome (SW)

A newborn is examined in the nursery by the pediatrician. The patient is a product of a term spontaneous vaginal delivery without complications. On physical examination, the patient is noted to have a facial nevus.

 

•      Facial nevus (port wine stain), seizures, hemiparesis, intracranial calcifications, and mental retardation

• Nevus is always present at birth and always involves at least the upper face and eyelid
• Glaucoma in ipsilateral eye
• Presentation
  • Seizures in most (focal tonic-clonic, contralateral to the nevus); becomes refractory and slowly develops hemiparesis, mental retardation
• Diagnosis

–     Skull x-ray shows occipital-parietal calcifications (serpentine or railroad- track appearance) and intraocular pressure reading initially (­)

• CT scan to highlight extent and show unilateral cortical atrophy and hydro- cephalus ex vacuo

• Treatment
  • Conservative if seizures are well controlled and development is not severely affected
  • Hemispherectomy or lobectomy—may prevent mental retardation and recalci- trant seizures if done in the first year of life
  • Regular intraocular pressure evaluation
  • Nevus—pulsed laser
  • Special education

 

ENCEPHALOPATHIES

 

Cerebral Palsy

• Group of motor syndromes from disorders of early brain development
  • Neurologic function may change or progress with time
  • Some have cognitive dysfunction

 

 

 

 

 

 

 

Note

Not all babies with a facial nevus have Sturge-Weber syndrome. Obtain a skull x-ray and intraocular pressure.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Note

There are four types of cerebral palsy:

• Spastic dysplasia
• Spastic quadriplegia
• Spastic hemiplegia
• Extrapyramidal

It is not essential to know these for the exam.

 

 

–     Most born at term with uncomplicated labor and delivery

° Majority have no identifiable antenatal problems

° Only 10% with intrapartum asphyxia

• The most obvious manifestation is impaired ability of voluntary muscles (rigid- ity and spasticity).
  • Other associations¾seizures and abnormalities of speech, vision, and intellect
• Other risk factors—increased risk with intrapartum infection, low birth weight (especially <1,000 g); most of these secondary to intraventricular hemorrhage and periventricular leukomalacia
• Diagnosis
  • MRI (location and extent of lesions or abnormalities)
  • If spinal involvement, MRI of spine
  • Hearing and visual evaluation
  • Genetic evaluation
  • Complete neurologic and developmental exams
• Treatment
  • Multidisciplinary team
  • Teach daily activities, exercises, assistance and adaptive equipment, surgical release procedures, communication equipment
  • Spasticity drugs (dantrolene, baclofen, botulinum toxin)
  • Psychological support

 

NEURODEGENERATIVE DISORDERS

 

Hallmark

•      Progressive deterioration of neurologic function

• Loss of speech, vision, hearing, and/or walking
• Associated with seizures, feeding difficulties, and cognitive dysfunction
• Regression of developmental milestones

 

Friedrich Ataxia

• Abnormal gene encoding for frataxin; autosomal recessive
• Onset of ataxia before <10 years of age
  • Slowly progressive
  • Loss of DTRs
  • Extensor plantar reflex
  • Weakness in hands and feet
  • Degeneration of posterior columns¾loss of position and vibration sense

•      Explosive, dysarthric speech

• Skeletal abnormalities, g., kyphoscoliosis

•      Hypertrophic cardiomyopathy¾refractory congestive heart failure, death

 

 

Wilson Disease

• Inborn error of copper metabolism; autosomal recessive
• Liver with or without CNS disease (neurologic, psychiatric)
• Liver symptoms first (any liver pathology), neurologic symptoms later (adolescent to adults)
  • Dystonia, tremors, basal ganglia problems
  • Kayser-Fleischer rings—pathognomonic (all will have with neuropsycho symp- toms)
  • MRI shows dilated ventricles with atrophy of cerebrum and lesions in thalamus and basal ganglia

•      Diagnosis—Suspect in any child with acute or chronic liver disease, unexplained neurologic disease, or behavioral or psychiatric changes

• Best screen—serum ceruloplasmin (decreased)
• Confirm with liver biopsy—increased Cu content
• Screen family members

• Treatment
  • Chelation with penicillamine (slows progression)
  • Definitive treatment with liver transplant

 

Sphingolipidoses

Tay-Sachs disease

• Deficient b-hexosaminidase-A, accumulate GM2
• Mostly in Ashkenazi Jews (carrier rate 1 in 30)
• Normal developmental until 6 months, then lag and lose milestones
• Seizures, hypotonia, blindness

•      Cherry-red macula

 

Purine Metabolism Disorders

Lesch-Nyhan disease

• X-linked
• Purine metabolism disorder of purine metabolism → excess uric acid
• Delayed motor development after a few months
• Self-mutilation and dystonia, gouty arthritis, tophi, renal calculi
• Choreoathetosis, spasticity
• Diagnosis–Analyze HPRT enzyme
• Treatment
  • Manage renal complications, arthritis
  • Behavioral modification
  • Medication for reduction of anxiety and mood stabilization

 

 

NEUROMUSCULAR DISEASE

 

Spinal Muscle Atrophy (SMA)

A pediatrician examines an infant who is on the examination table in frog-leg position, with subdiaphragmatic retractions and absent tendon reflexes.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Note

Transient neonatal myasthenia

• Neonates born to mothers with myasthenia;

may have generalized hypotonia and weakness, feeding difficulties, and respiratory insufficiency from days to weeks

• May need ventilation and nasogastric feedings
• After antibodies wane, they are normal and have no risk for

•      Degenerative disease of motor units beginning in the fetus and progressing into infancy; denervation of muscle and atrophy

• Types

–     SMA 1 = severe infantile (Werdnig-Hoffman disease)

• SMA 2 = late infancy, slower progression
• SMA 3 = chronic juvenile (Kugelberg-Welander disease)

• Autosomal recessive
• Clinical presentation—SMA 1 presents in early infancy with
  • Progressive hypotonia; generalized weakness; Infant is flaccid, has little move- ment and poor head control

–     Feeding difficulty

• Respiratory insufficiency
• Fasciculations of the tongue and fingers
• Absent DTRs

• Typically appear brighter than others of same age
• Diagnosis

–     Simplest, most effective diagnosis is molecular genetic marker in blood for the SMN gene.

• EMG—fibrillation potential and other signs of denervation
• Muscle biopsy shows a characteristic pattern of perinatal

• Treatment is supportive; there is no cure; most die in first 2 years of life

 

Myasthenia Gravis

A pediatrician examines an infant with poor sucking and swallowing since birth. The infant is noted to be a floppy baby with poor head control. There is associated ocular ptosis and weak muscles on repeated use.

 

• Immune-mediated neuronal blockade; motor end plate is less responsive due to decreased number of available acetylcholine receptors secondary to circulating receptor binding antibodies; generally nonhereditary
• Clinical presentation

–     Ptosis and extraocular muscle weakness is the earliest and most consistent finding.

• Dysphagia and facial weakness, and early infant feeding difficulties
• Poor head control

 

 

• Limb-girdle weakness and in distal muscles of hands
• Rapid muscle fatigue, especially late in the day
• May have respiratory muscle involvement

• Diagnosis
  • EMG more diagnostic than muscle biopsy—decremental response to repetitive nerve stimulation, reversed after giving cholinesterase inhibitor (edrophonium)

→ improvement within seconds

• CPK is
• May have anti-acetylcholine (anti-ACh) antibodies (inconsistent)

• Treatment
  • Mild—many need no medication
  • Cholinesterase-inhibiting drugs—either neostigmine bromide PO or pyr- idostigmine
  • Severe—long-term prednisone; if no response, intravenous immunoglobulin (Ig), then plasmapheresis
  • Thymectomy—most effective if patient has high anti-ACh titers and symptoms for <2 years
• Complications—do not tolerate neuromuscular blockade and aminoglycosides potentiate

 

Hereditary Motor-Sensory Neuropathies (HMSNs)

HMSN I: Marie-Charcot-Tooth disease

• Progressive disease of peripheral nerves; peroneal muscle atrophy; peroneal and tibial nerves
• Autosomal dominant
• Clinical presentation
  • Asymptomatic until late childhood or adolescence but may have problem with gait as early as age 2 years

–     Clumsy, fall easily; muscles of anterior compartment of lower leg become wasted → stork-like appearance

• Pes cavus, foot drop
• Claw hand (in worse cases)
• Slowly progressive through life, but normal lifespan and remain ambulatory

• Diagnosis
  • CPK is
  • Decreased nerve conduction velocities (motor and sensory)
  • Sural nerve biopsy is
  • Blood molecular genetic diagnosis
• Treatment

–     Stabilize ankles

• Surgical ankle fusion
• Protection from trauma
• If sensory problems, phenytoin or carbamazepine

 

 

Guillain-Barré Syndrome

• Postinfectious polyneuropathy—mostly motor; all ages; most with demyelinating neuropathy
• 10 days after a nonspecific viral illness or Campylobacter jejuni or Mycoplasma pneumoniae—Landry ascending paralysis
  • Symmetric proximal and distal muscles
  • Gradually over days to even weeks

–     May have tenderness, pain, paresthesias early

• Bulbar involvement in half—dysphagia, facial weakness, respiratory insuffi- ciency
• May have autonomic involvement—blood pressure lability, bradycardia, asystole
• Spontaneous recovery begins in 2–3 weeks; some have residual weakness; improvement in inverse direction

• Diagnosis
  • Significant increase in CSF protein with normal glucose and no cells
  • Reduced motor and sensory nerve conductions
• Treatment
  • Mostly supportive
  • Admit all patients (observe respiratory effort)
    • Mild-observation
  • Intravenous immunoglobulin 2–5 days
  • May need plasmapheresis, steroids, interferon, or other immunosuppressives

 

Muscular Dystrophies

Duchenne

A 3-year-old boy is brought to the pediatrician because the patient is very clumsy. According to the young boy’s parents, he is having difficulty climbing stairs and frequently falls. On physical examination, hypertrophy of the calves is noted.

 

• Primary myopathy with genetic basis; is progressive and results in degeneration and death of muscle fibers; most common of the neuromuscular diseases in all races and ethnic groups; X-linked recessive
• Clinical presentation
  • First sign may be poor head control in
  • By year 2, may have subtle findings of hip-girdle weakness
  • Gower sign as early as age 3 years but fully developed by age 5–6 years; with hip-waddle gait and lordotic posturing
  • Calf pseudohypertrophy (fat and collagen) and wasting of thigh muscles
  • Most walk without orthotic devices until age 7–10 years, then with devices until 12; once wheelchair-bound, significant acceleration of scoliosis

 

 

• Progressive into second decade:

• Respiratory insufficiency
• Repeated pulmonary infections
• Pharyngeal weakness (aspiration)
• Contractures
• Scoliosis (further pulmonary compromise)

° Cardiomyopathy is a constant feature.

° Intellectual impairment in all; IQ <70 in about 30%; most with learning disabilities

 

 

 

 

Figure 21-3. Gower Sign in Duchenne Muscular Dystrophy

 

 

 

• Death usually around 18 years of age from respiratory failure in sleep, intrac- table heart failure, pneumonia, aspiration with obstruction
  • Lab studies
    • CPK—15,000–35,000 U/L (normal is <160 U/L) (initial screen for myopathy)

–     Best initial test—molecular genetic diagnosis: deficiency or defective dystro- phin cytoskeletal protein from gene at Xp21.2 (one-third will not be diagnostic)

• Muscle biopsy to show the abnormal or absent dystrophin; most accurate test (do in the one-third who do not give a molecular diagnosis)

• Treatment—multidisciplinary team
  • Digoxin for heart failure (all patients need cardiology referral)
  • Vigorous treatment of pulmonary infections
  • Maintain good nutrition; good calcium supply (prevent osteoporosis)
  • Physiotherapy—delay contractions; orthotic devices, proper wheelchair, physiatrist