Common Neurologic

Disorders

PEARL JOY L. SENDAYDIEGO

Pediatric Neurologist
HEADACHE
Temporal Pattern of Headache

Acute

Acute
Symptoms

recurrent
Chronic
progressive
Chronic non-
progressive
Mixed

Time
ACUTE HEADACHE
Generalized
¨ Systemic infection
• Toxins: lead, CO2
¨ Meningitis
¨ Hemorrhage •Electrolyte imbalance
¨ Thrombosis/Embolic •Postseizure
¨ Migraine
•Collagen disease
¨ Hypertension
¨ Trauma •Exertional
¨ Substance Abuse
¨ Medications
ACUTE HEADACHE
Localized
¨ Sinusitis
¨ Otitis
¨ Ocular abnormality (EOR, strabismus)
¨ Dental disease
¨ Trauma
¨ Occipital neuralgia
¨ TMJ dysfunction
¨ Malocclusion of the teeth
ACUTE RECURRENT
HEADACHE
¨ Migraine
¨ Migraine Variants
¨ Tension-type
¨ Cluster Headache
¨ Neuralgias
¨ Hypertension
¨ Medications
¨ Substance Abuse
¨ Epileptic variants
CHRONIC PROGRESSIVE
HEADACHE
¨ Hydrocephalus ¨ Brain abscess
– Obstructive ¨ Hematoma (subdural)
– Communicating
¨ Pseudotumor cerebri
¨ Neoplasm
– Medulloblastoma/ ¨ Aneurysm
PNET ¨ Malformations
- cerebellar astrocytoma – Chiari
- Ependymoma – Dandy Walker
- Pineal region tumor
¨ Hypertension
- Craniopharyndioma
- astrocytoma ¨ medications
CHRONIC NONPROGRESSIVE
HEADACHE
¨ Muscle contraction headache
¨ Conversion
¨ Malingering
¨ Postconcussion
¨ Depression
¨ Anxiety
¨ Adjustment reaction
Headache History
¨ Character of the headache
¨ Identify trigger factors
¨ Relieving/aggravating factors
¨ Any other medical problems
¨ Family history of headache

The examiner should have tentatively classify

the headache type after the history taking.
Headache Danger Signals
¨ Progressive headache whether acute or
chronic
¨ Sudden onset of severe headache unrelieved
by rest and analgesics
¨ Headache precipitated or aggravated by
exertion, coughing or straining
¨ Nocturnal or morning headache
Headache Danger Signals
¨ Symptoms ¨ Signs of increased ICP
– Fever – Changes in sensorium
– Behavioral and/or – Papilledema
sensorial changes – Anisocoria
– Visual disturbance – Bilateral CN VI palsy
– Motor and/or sensory – Hypertension
disturbance
Other signs
– Gait disturbance
– Focal neurologic
– Language/speech deficit
disturbance
– Nuchal rigidity
– Seizure
– Diminution of normal
abilities Less than 5 year old should
be investigated further.
Etiology of Headache
¨ Acute headache in children and adolescents
presenting to the ER
– 2-6% of ER visits are due to headache
7% 3%
10% URTI
Migraine
Meningtis
19% 61% Undeterm
Tumors

Lewis and Qureshi, 2000

Diagnostic Criteria for Migraine
Headaches in Children
¨ Recurrent headache
¨ Symptom free intervals
¨ Three of the following:
– Abdominal pain, nausea or vomiting with headache
– Hemicrania
– Throbbing, pulsatile headache
– Complete relief after rest
– Visual, sensory or motor aura
– History of migraine in one or two members of the
immediate family
Prensky and Sommer, 1979
Classification of Headache
PRIMARY SECONDARY
intrinsic to the nervous
develop in close temporal
system
relationship to the
underlying condition
¨ Migraine and/or successfully
¨ Tension-type headache resolve with treatment of
(TTH) the condition
¨ Trigeminal autonomic
cephalalgias (TACs)
¨ Other primary
headache disorders
Migraine without aura
• Most common form of migraine in children and
adolescents.
• No aura occurs, instead children demonstrate
prodromal personality changes such as irritability
and lethargy and are also unusually pale or have
dark circles under their eyes. This lasts for about
30 minutes.
• Headache follows, usually generalized, bifrontal
or bitemporal, associated with loss of appetite,
abdominal pain, nausea and vomiting.
Children and adolescents < 18 years
¨ 2- 72 hours (untreated or unsuccessfully treated
headache)
¨ Young children: commonly bilateral
Migraine with aura
• usually preceded by a visual aura lasting less than
20 minutes, described as blurred vision, brightly
colored lights, scotoma, moving lights, and
fortification spectra.
• If the aura is lateralized, the headache is
contralateral described as severe and throbbing or
pounding, most commonly located in the frontal,
temporal or orbital area.
Diagnostic Tools
¨ Neuroimaging
High priority
- chronic progressive headache
- acute headache described as the worst headache
of his life, thunderclap headache
- abnormal neurologic exam
- focal neurologic deficit
- (+)Ventriculoperitoneal shunt
- neurocutaneous syndrome
- age <3 y/o
¨ Neuroimaging
Moderate priority
- Headache or vomiting on awakening
- Focal headache
- Meningeal signs
- Comorbid seizures

To assure an anxious patient or relative

¨ A. Computed Tomography (CT scan)
¨ B. Magnetic Resonance Imaging (MRI)
¨ C. X-ray- cervical, skull, sinus
¨ D. Ultrasound- carotid and vertebral, TCD

¨ CSF studies- CNS infx, SAH, ICP

¨ EEG
Management of Headache in
Children
¨ A. Abortive agents
1. Sumatriptan (Imigran)
2. Isometheptene mucate/Paracetamol
(Midrid)
3. Ergotamine (Avamigran)
4. DHE nasal spray and inj (NA)
5. Steroids (Prednisone and
Dexamethasone)
¨ B. Anti-emetics:
¨ C. Analgesics- for migraine and tension HA
1. Acetaminophen 10-15 mg/kg/dose
2. Ibuprofen 5-10 mg/kg/dose
3. Naproxen sodium 10-20 mg/kg/day
¨ D. Prophylactic agents
1. ß-blockers- Propranolol 1-2 mg/kg/day
2. Ca++ channel blocker- Flunarizine 5 mg/day
3. Appetite stimulant- Pizotifen 0.5 mg daily
4. Antihistamine and serotonin antagonist
Cyproheptadine (Periactin)
5. Anticonvulsants
Carbamazepine: 20-40 mg/kg/day
Valproic acid: 10-20 mg/kg/day
Phenytoin: 3-7 mg/kg/day
Topiramate, Lamotrigine, Gabapentin,
Levetiracetam
6. Antidepressants
Amitriptyline (Limbitrol)/Nortriptyline
SSRIs (Prozac, Zoloft)
7. NSAID- Naproxen Sodium
Altered Level of
Consciousness
Consciousness
¨ State of awareness of self and environment
¨ Fully alert:
– Normally aware of self and environment
– Oriented to time, person and place
– Performs age-appropriate tasks
Altered States of Consciousness
¨ Confusion/Delirium
¨ Lethargy
¨ Obtundation
¨ Stupor
¨ Coma
¨ Confused- able to maintain wakefulness but
nor fully oriented; can follow simple but not
complex tasks
¨ Delirium- agitated form of confusion
¨ Lethargy- unable to maintain wakefulness
unless receiving stimuli, unable to perform
complex tasks
¨ Obtundation- roused to verbally responsive
state only by noxious stimuli, drifts back to
unconscious state quickly when stimulus is
withdrawn
¨ Stupor- responds to persistent noxious
stimuli with semi-purposeful avoidance and
vocalizations only
¨ Comatose- unarousable even with noxious
stimuli, may respond with decortication or
decerebration
Neuroanatomic Substrates of
Arousal/Consciousness
¨ Bilateral hemisphere
¨ Brainstem ascending reticular activating
system
Glasgow Coma Scale for Children
¨ Eyes open
¨ Best Motor Response
– Spontaneously 4 – Obeys commands 5
– To speech 3 – Localizes pain 4
– To pain 2 – Flexion to pain 3
– None 1 – None 1

¨ Best verbal response

– Oriented 5
– Words 4
– Vocal sounds 3
– Cries 2
– None 1
Abnormal Respiratory Patterns
¨ Cheyne-Stokes breathing- forebrain damage
¨ Central neurogenic hyperventilation-
hypothalamic-midbrain damage
¨ Apnea; cluster breathing- lower pons
¨ Ataxic breathing- medulla
Pupillary size and reaction
¨ Anisocoria- uncal herniation
¨ Small, reactive- metabolic, diencephalic
compression
¨ Pinpoint- pons
¨ Midposition, fixed- midbrain
¨ Large, fixed- tectal
Acid-Base Abnormalities in a
Comatose Child
¨ Metabolic acidosis ¨ Repiratory acidosis
– Diabetic ketoacidosis – Respiratory failure
– Diabetic hyperosmolar – Sedative drugs
coma
– Brainstem injury
– Lactic acidosis
– Uremia
– Seizures
– Acidic poisons ¨ Mixed (met acid and
– Salicylism resp alka)
¨ Respiratory alkalosis – Salicylism
– Hepatic failure – Sepsis
– Sepsis – Hepatic failure
– Pneumonia
Management
¨ Airway
¨ Maintain circulation
¨ Give glucose
¨ Decrease ICP
¨ Control seizures
¨ Treat infection
¨ Restore acid-base balance and electrolyte
balance
Management
¨ Adjust body temperature
¨ Administer thiamine
¨ Consider specific antidotes
¨ Control agitation
Increased Intracranial Pressure
Monro- Kellie hypothesis
¨ Skull is a rigid cavity with relatively non-
compressible components
¨ Components of the cranium:
– CSF
– Blood
– Brain Parenchyma
 C = dV/ dP
¨ ICP and blood flow to the brain
C – compliance
dV- change in volume
dP- change in pressure
Pressure volume curves
60

50
ICP
40
mm
Hg 30 0 Infant
20 14 y/o
20

10

0
1 3 5 6 7 9

Change in volume (ml)

S/S of increased ICP
¨ History
– Headaches of recent onset and increasing
severity
– Associated nausea, vomiting
– Transient visual obscuration
– Infant: poor feeding, vomiting, excessive
irritability, lethargy
S/S of increased ICP
¨ Signs
– <3 y/o: excessive head growth, separated
sutures, full or bulging fontanel, sunset eyes,
brisk reflexes in the lower extremities
– >3 y/o: papilledema, bilateral VI palsy,
Parinaud’s syndrome, brisk reflexes, truncal
ataxia, head tilt
Etiology of Increased ICP
¨ Posterior Fossa tumors: (Menkes)
– Medulloblastoma 32.4 (%)
– Pilocytic astrocytoma 28.3
– Ependymoma 12
Etiology of Increased ICP
¨ Pseudotumor Cerebri
– Chronic headache, occasional vomiting, blurred
vision
– Papilledema, bilateral VI palsy
– Cause: steroid withdrawal, excessive vitamin
A, otitis media and mastoiditis
– Associated with obesity, endocrine disorders,
SLE
Papilledema
Management of Increased ICP
¨ Correction of etiology!
¨ Supportive therapy
– Maintain pO2 100-150, pCO2 25-30
– Maintain CPP, head elevation at 30°
– Restrict fluids
– Nutrition: protein 1.5 x resting metabolic req,
serum albumin > 3 g/dl
Management of Increased ICP
¨ Manual hyperventilation
¨ Mannitol 2.5-5cc (0.25-1.5 g/kg/dose)
bolus
¨ Dexamethasone 0.5 – 1 mg/kg/day
¨ Acetazolamide + furosemide
¨ Pentobarbital
¨ Morphine
¨ Hypothermia
Movement Disorders
Epileptic or Non-epileptic
Paroxysmal Disorders

Epilepsy

Syncope Stereotypies

Movement Disorders Behavioral Disorders

Diagnosis of a Movement Disorder
¨ Identifying the type and pattern of the
movement disorder
¨ Determining whether it is an isolated
movement disorder or is associated with
other neurological signs
¨ Delineating the probable etiology
(hereditary, sporadic, primary or secondary
to a known neurological disease)
Movement Disorders
¨ Disorders of motor control
¨ Types:
– Hypokinetic (decreased movement)
– Hyperkinetic (increased movement)

• Movement disorders in children are

mostly hyperkinetic.
Pullman, 1999
Hypokinesias
¨ Parkinson’s disease
¨ Symptomatic parkinsonism
¨ Parkinsonism Plus
Hyperkinesias
¨ Akathisia ¨ Myoclonus
¨ Ataxia ¨ Moving toes/fingers
¨ Athetosis ¨ Paroxysmal
¨ Ballism dyskinesias
¨ Chorea ¨ Restless legs
¨ Dystonia ¨ Stereotypy
¨ Hemifacial spasm ¨ Tics
¨ Hyperekplexia ¨ Tremors
¨ Hypnagogic
dyskinesias
Ataxia
¨ Congenital anomalies- Dandy-Walker,
Chiari malformation, encephalocoele,
agenesis of vermis (Joubert disease)
¨ Infection- acute labyrinthitis, cerebellar
abscess, acute cerebellar ataxia
¨ Toxic causes- alcohol, thallium, AED
¨ Brain tumors
¨ Metabolic disorders- abetalipoproteinemia,
arginosuccinic aciduria, Hartnup disease
Ataxia
¨ Degenerative diseases
– Ataxia telangiectasia
– Friedrich ataxia
– Roussy-Levy disease
– Ramsay Hunt syndrome
– Olivopontocerebellar atrophies (OPCA)
– Vitamin E deficiency
– Pelizaeus-Merzbacher disease
– Neuronal ceroid lipifuscinosis
– Late onset GM2 gangliosidoses
Chorea
¨ Consists of a single, isolated muscle action,
producing a short, rapid, uncoordinated jerk
of the trunk, limb or face. The successive
occurrence of two or more such isolated
movements can result in a complex
movement pattern, and the superimposition
of these movements on normal movement
can cause a dance-like gait.
Klawans, 1992
Chorea
¨ Sydenham’s Chorea (St. Vitus Dance)
– Streptococcal infection/ rheumatic fever
– Onset usually after 3 years, mostly girls
– Hypotonia, chorea and emotional lability
– “milkmaid’s grip”, “choreic hand”, “darting
tongue”, “pronator sign”
– May persist for 1-2 years, and 20% may recur
– Diazepam, Phenothiazines, Haloperidol
Chorea

¨ Huntington disease
– Autosomal dominant trait, located on 4p 16.3
– Progressive chorea and presenile dementia,
between 35 and 55 years of age
– Rare in pediatrics, <1% have onset prior to
10 years, manifesting as rigidity and dystonia
– GTC Szs are common and resistant to AED
– More rapid course in children (8 years)
– Atrophy of the caudate nucleus and putamen
Dystonia
¨ Twisting movements that tend to be
sustained at the peak of movement
¨ Frequently repetitive
¨ Often progress to prolonged abnormal
postures
Dystonia
¨ Primary Dystonias (idiopathic)
¨ Secondary Dystonias (symptomatic)
Dystonia
¨ Dystonia musculorum deformans
– Abnormality of catecholamine metabolism
has been proposed
– Autosomal dominant, gene mapped to ch
9q34
– Initial unilateral posturing of the lower
extremity, later involving all 4 extremities,
and even the muscles of swallowing
– Treated with trihexyphenidyl,
carbamazepine, levodopa, bromocriptine,
diazepam
Dystonia
¨ Wilson’s disease
– Dystonia and EPS
– Mental deterioration and behavioral disorders
– Slit-lamp exam: Kayser-Fleischer ring
– Labs:
• urinary copper
• serum copper
• serum ceruloplasmin
• Symmetrical areas of hypodensity in the thalamus
and basal ganglia
Dystonia
¨ XDP
– Sex-linked (Xq13.1)
– Adult onset (2 cases with onset of 12 and 15
years)
– Predominantly male
– Dystonia and Parkinsonism
– Caudate and putamen atrophy on MRI and
pathology
Dystonia
¨ Leigh’s Disease (Subacute Necrotizing
Encephalomyelopathy)
– Progressive neurological deterioration
– Loss of motor milestones
– Basal ganglia and brainstem lesions
– Reduction of cytochrome C oxidase
Athetosis
¨ Irregular, often continuous, writhing
movement of the extremities, primarily the
distal portion
¨ Pseudoathetosis is now replaced with
dystonia
¨ Usually associated with perinatal asphyxia,
infectious cause (viral encephalitis), inborn
error of metabolism (PKU), Wilson disease
Tremor
¨ Postural
– 6-12 Hz
– Essential and physiologic tremor
– Seen in children under stress, drug effect
¨ Rest
– 4-5 Hz
– Occurs in Parkinsonism
¨ Intention
– 3-4 Hz
– Disease of the cerebellum or cerebellar pathways
 Tremor

TREMOR

Postural Resting Intention

DRD
Cerebellar
Drugs Huntington disease
Essential lesions
Wilson’s disease
Juvenile Parkinson’s
Physiologic Hallervordan Spatz
Tremor
¨ Drugs associated with Tremors
– Valproic acid Amphetamines
– Lithium Steroids
– Theophylline
– Beta agonists
– Caffeine
– Anticholinesterase
– TCA
Pediatric Annals, 1997
Tics
¨ Sudden, brief, repetitive, nonrhythmic and
stereotyped movements or vocalization
¨ Typical tics
•Blinking Sniffing
•Eye rolling Shoulder shrugging
•Mouth opening Throat clearing
•Grunting
¨ Complex tics
•Head shaking Kicking
•Trunk bending Complex vocalization
Tics
¨ Tourette Syndrome
– Motor and/or vocal tics such as grunting,
coughing, sneezing, and barking, to coprolalia
or compulsive echolalia
– Onset before age 18 years; boys: girls, 3-5:1
– Comorbidity: ADHD, OCD
– Most responsive to opamine receptor
antagonists
Myoclonus
¨ Sudden shock-like involuntary movement
that may affect a single body region, a
segment or the entire body
¨ Types of myoclonus:
– Cortical
– Brainstem
– Spinal
Myoclonus: etiology
¨ Physiologic
¨ Essential
¨ Epileptic
¨ Myoclonus associated with ataxia, +/- Szs, +/-
dementia
– Lafora body GM2 gangliosidosis
– Ceroid lipofuscinosis Ataxia Telangiectasia
– Unverricht-Lundberg Ramsay-Hunt
– MERRF Biotinidase deficiency
– Sialidosis Carboxylase deficiency
Myoclonus: etiology
¨ Acquired
– Viral: SSPE, HIV, Herpes simplex
– Metabolic: renal failure, hepatic failure, hyperglycemia
– Polyminimyoclonus: neuroblastoma, opsoclonus-
myoclonus syndrome
– Hypoxia
– Head trauma
– Stroke
– tremor
Myoclonus: etiology
¨ Acquired
– Drugs
• TCA
• Levodopa
• Lithium
• Penicillin
• Anticonvulsants
Stereotypy
¨ Simple or complex movements that repeat
themselves continually and identically
¨ Seen in Rett syndrome, autism, mental
retardation, schizophrenia, TD and Lesch-
Nyhan syndrome
Stereotypy
¨ Rett Syndrome
Criteria
– Normal prenatal and perinatal history
– Postnatal deceleration of head growth
– Loss of purposeful hand skill
– Stereotypic hand movements
– Autism
– Dyspraxia
Weakness
Swaiman’s Pediatric Neurology. – 5th ed.
Clinical Manifestations
¨ Hypotonia
¨ Decreased motor power
¨ Hyporeflexia/areflexia
¨ Muscle atrophy
¨ (+) Fibrillations/fasciculations
Diagnostic tools
¨ Muscle enzymes: CPK
¨ EMG/NCV
¨ Muscle biopsy/Nerve biopsy
¨ Muscle UTZ
 Lower Motor Neuron lesion

AHC PN NMJ MSC

Weakness Prox Distal Episodic Prox

Atrophy (+) Early, (-) Pseudohy

severe pertrophy
Reflexes Dec/0 Dec/0 N or 0 N/dec

Sensory N Dec/0 N N
 Disorders of Anterior Horn Cell
Spinal Muscular Atrophy
¨ Progressive degeneration of the AHC and cells of
the motor cranial nuclei
¨ Autosomal recessive transmission; caused by a
mutation in the telomeric survival motor neuron
gene (SMN1)
¨ Normal to slightly enzymes
¨ Decreased NCV
¨ Denervation on EMG- fibs and fasciculations,
polyphasic MUPs, increased in amp and duration
¨ Muscle biopsy: denervation atrophy with
clustering of type I and II muscle fibers;
Disorders of Anterior Horn Cell
Spinal Muscular Atrophy
3 types based on the age of onset:
¨ Werdnig-Hoffman (Infantile SMA)
– Onset at birth or <6 months of age
– Usually die before age 3
– Weakness pronounced over the proximal >
distal muscles
– Pure motor involvement, sensory intact
– Intelligence is normal
Disorders of Anterior Horn Cell
Spinal Muscular Atrophy
¨ Byers-Bankers (Intermediate form)
¨ Kugelberg-Welander (Juvenile form)
¨ Diagnosis: Molecular genetic testing
SMN1 deletion/mutation SMN2 copy number testing
(gold standard)
Muscle Biopsy, EMG-NCV
¨ Treatment: mainly supportive, but novel disease-
modifying therapies
with nusinersen, onasemnogene abeparvovec,
and risdiplam
¨ Nusinersen: antisense oligonucleotide that
modifies splicing of the SMN2 gene to increase
production of normal, full-length survival motor
neuron protein, which is deficient in SMA
¨ Onasemnogene abeparvovec is a
recombinant adeno-associated viral vector
containing complementary DNA encoding
the normal human survival motor neuron
protein (SMN1)
¨ Risdiplam is a small molecule SMN2
splicing modifier that binds two sites
in SMN2 pre-messenger RNA, thereby
correcting the splicing deficit of SMN2,
leading to increased levels of full-length
SMN protein.
Disorders of Anterior Horn Cell
Poliomyelitis
¨ Brief febrile illness
¨ No history of immunization
¨ Asymmetric muscle weakness
¨ CSF pleocytosis
¨ Treatment: supportive
Disorders of the Peripheral Nerve
Guillain Barre Syndrome
¨ Autoimmune disorder
¨ May be preceded by a nonspecific febrile
illness, GI or respiratory
¨ Followed by ascending, symmetric muscle
weakness, may involve the face and bulbar
muscles, and respiratory involvement are
not uncommon
¨ Some may have mild sensory complaints
Disorders of the Peripheral Nerve
Guillain Barre Syndrome
¨ CSF: cytoalbuminologic dissociation
¨ EMG-NCV is diagnostic: denervation
potentials and delayed conduction velocities
¨ Treatment: supportive, IVIg,
plasmapharesis
 Disorders of the Peripheral Nerve
Hereditary Sensory Motor Neuropathy
(HSMN)
¨ Charcot Marie Tooth disease or
peroneal muscular atrophy (HSMN
I)
– Autosomal dominant transmission
– Distal weakness of the feet during the
first decade, with associated sensory
deficits
– Pes cavus and stork-leg appearance,
palpable enlarged nerves
Disorders of the Peripheral Nerve
HSMN I
¨ Pathology: Extensive segmental
demyelination and remyelination
¨ EMG: denervation potentials
¨ NCV: delayed conduction
¨ Nerve biopsy: onion-bulb appearance of
nerve fibers
Disorders of NMJ
Myasthenia Gravis
¨ Autoimmune disease in which
antibodies develop against
acetylcholine receptor protein of
the motor end plate
¨ Present as weakness particularly
at the end of the day
¨ Painless muscle weakness-
invariably transient, recovery
with rest
¨ Diplopia, ptosis, drooping head,
snarl, jaw drop, dysphagia,
dysphonia, dyspnea, respiratory
failure
Disorders of NMJ
Myasthenia Gravis
¨ Neonatal: born of myasthenic mothers, symptoms
appear during the 1st week to 2 months of life
¨ Congenital: (-)maternal history for MG, symptoms
usually occur before age 1, presents with ptosis ff.
by swallowing difficulties and truncal weakness.
(+) Hx of decreased fetal movement, feeding
difficulties and weak cry usually present.
¨ Juvenile: as in adult, onset at age 2 and peak at 10-
20 years of life; 70-90% are positive for antibody
assay against Ach receptor
Disorders of NMJ
Myasthenia Gravis
Diagnostics:
¨ Tensilon test (Edrophonium Cl)- short acting
anticholinesterase, improvement seen in 30-60
seconds, last for 4-5 minutes. (Neostigmine-
longer acting)
¨ Repetitive nerve stimulation test (RNS)-
decremental response to repeated stimulation
¨ Single fiber EMG
¨ (+) Ach receptor antibody titer in serum
Treatment: Pyridostigmine (Mestinon)
Disorders of NMJ
Myasthenia Gravis
¨ Drugs which can unmask MG:
penicillamine, b blocker, carnitine,
aminoglycoside, lithium carbonate, Mg
salts, tremethadione and phenytoin
Treatment: Pyridostigmine bromide
(Mestinon)
Disease of Muscle
Duchenne Muscular Dystrophy
¨ X-linked recessive, gene defect located at
Xp21, causing absent or deficient
dystrophin
¨ Presents as clumsiness in the early stage
¨ Proximal muscle weakness, manifested by
(+)Gower’s sign
¨ Male child who does not walk by age 18
months, wheelchair bound by age 12
¨ Mentally subnormal
Disease of Muscle
Duchenne Muscular Dystrophy
¨ Muscles degenerate and are replaced by fatty
tissue (pseudohypertrophy)
Diagnostics:
¨ CPK- markedly elevated
¨ EMG- myopathic changes, small amplitude
potentials; NCV- normal
¨ Muscle biopsy- breakdown of the muscle
membrane, decreased no. in muscle cells and
variability of muscle fiber size, infiltration of
collagen and fat cells
Disease of Muscle
Duchenne Muscular Dystrophy
Complications:
¨ Compromised pulmonary function
¨ Cardiomyopathy
Treatment:
Glucocorticoids are the mainstay of
pharmacologic treatment for DMD
 Disease of Muscle
Duchenne Muscular Dystrophy
¨ indicated for children with DMD and should be
started before there is substantial physical decline
¨ For children with DMD age 4 years or older
whose motor skills have plateaued or have started
to decline: oral prednisone or deflazacort.
¨ dietary calcium and vitamin D supplementation
¨ yearly dual-energy x-ray absorptiometry (DXA)
scanning and a 25-hydroxyvitamin D level
¨ Genetic therapies that involve exon skipping
(eteplirsen, golodirsen, viltolarsen) or read-
through of premature termination codon
(ataluren) approved in some countries
¨ eteplirsen exon 51 skipping; ongoing trial for
clinical benefit
¨ Golodirsen viltolarsen :antisense oligonucleotide
that is designed to modify the splicing of exon 53
of dystrophin pre-messenger RNA, resulting in
exon 53 skipping in patients with amenable
pathogenic variants of the dystrophin gene;
clinical benefit unproven
¨ Ataluren — orally administered drug being
developed for the treatment of genetic
defects caused by nonsense (stop)
mutations; clinical benefit of ataluren is not
yet established
Spinal Cord Diseases
Brain Spinal cord
¨ Changes in mental ¨ MS is preserved
status ¨ CN not involved,
except for lower CNs
¨ CN involvement
(brainstem & upper
¨ Unilateral cervical lesions)
presentation (motor, ¨ Presentation in the
sensory) transverse plane
– Sensory level
– Symmetrical motor
involvement
¨ Urinary and bowel
involvement
Spinal cord Peripheral
Nerve
¨ Proximal motor ¨ Distal motor
weakness weakness
¨ Late atrophy ¨ Hypotonia, atrophy,
¨ Hyperreflexia hypo/areflexia
¨ Sensory level ¨ Sensory deficits
characterized by
dermatome,
myotome,
angiotome
Cervical lesions
¨ On the trunk, C4 and T2 dermatomes
are contiguous

¨ Rotating sign
Transverse Myelitis
¨ Focal inflammatory disorder of the spinal
cord resulting in motor, sensory and
autonomic dysfunction
¨ May be due to infection or parainfectious
etiology, connective tissue disease, SC
infarction, related to MS, idiopathic
Transverse Myelitis
¨ Exclusion:
– SC compression
– Syphilis
– Previous MS
– AVM
– Sarcoidosis
– HIV infection
Clinical Manifestations
¨ Most commonly affects the thoracic cord
¨ Affected extremities are initially flaccid
spastic
¨ +/- back pain
¨ Sensory level
¨ Bowel and bladder dysfunction
¨ Evolution over a few hours or progress over a
number of days
Differential Diagnosis
¨ Perivenous encephalomyelitis: affects
the brain and SC
– Acute disseminated encephalomyelitis
(ADEM)
– Post-infectious encephalomyelitis
– Post-vaccinial encephalomyelitis
– Acute hemorrhagic leukoencephalomyelitis
(AHLE)
Differential Diagnosis
¨ Multiple Sclerosis: clinical grounds,
imaging studies, immunologic
evaluation
¨ SLE: 1-3 % of SLE will develop TM
¨ Vascular malformations
– AVM or AVF: recurrent or ascending TM
– Dxtic: spinal angiogram
Diagnostic work-up
¨ Gd-enhanced MR scan of the SC
– T-2 signal abnormalities and slight Gd
enhancement extending over spinal
segments
– SC may be swollen in these regions
– Mild and partial cases may have normal
MR
¨ Rule out any surgically lesion
Diagnostic work-up
•CSF analysis

¨ Cell count, protein ¨ RT-PCR for

and glucose enteroviral RNA
¨ PCR for HSV-1, ¨ PCR for EBV DNA
HSV-2 DNA, VZV,
HIV, CMV ¨ VDRL, FTA-ABS
¨ HSV Ab ¨ Oligoclonal bands
¨ VZV Ab ¨ IgG
¨ Viral culture ¨ MBP
 SC infections in developing
countries Zunt, JR, AAN 2003

Etiology Dxtic test

TB CSF culture, AFB, adenosine deaminase
level, PPD
Neurosyphilis CSF: VDRL, FTA-ABS, MHA-TP
Schistosomiasis (+) eggs in stool/ granuloma/ (+)Ag in
serum or CSF
Nutritional def Serum B12
HIV myelopathy Serum HIV
Motor neuron dse EMG
SC compression neuroimaging
MS CSF oligoclonal bands, MRI, VER
CP history
 Treatment
¨ Methylprednisolone
– 1 g/1.73m2 x 3-5 days followed by oral prednisone
(1 mg/kg/day) for a total of 14 days
– MP group (5) compared with controls (10):
• Median time to walking independently was significantly
reduced
• Proportion of patients with full recovery within 12 months
was higher
• All patients had complete motor recovery within one year
compared to only 2/10 in the control
Sebire et al, 1997
Treatment
¨ Plasmapharesis after MP
¨ Acyclovir 10 mg/kg IV TID for 14-21
days
¨ Doxycycline or Azithromycin for
mycoplasma
¨ Ceftriaxone for Lyme disease
¨ Gancyclovir for CMV
Prognostication
¨ (+)Prognostic factors:
– More rapid progression of symptoms: X=4.3 days
– Back pain
– Spinal shock
¨ Diagnostic tests for prognostication:
– EMG: extensive denervation
– SSEP: (-)central motor conduction time
– MRI: signal abnormalities extending >10 segments
Multidisciplinary Approach
¨ Neurologist
¨ Physiatrist
¨ Urologist
¨ Psychologist/Psychiatrist
Management
¨ Rehabilitation
¨ Neuropathic pain- gabapentin, CBZ
¨ Spasticity
– Tizanidine
– Baclofen
Congenital Malformations of
the Central Nervous System
 Major Events in Human Brain Development
and Peak Times of Occurrence (Menkes)
Gestational Age in Months
Postnatal
1 2 3 4 5 6 7 8 9

Neurulation
(3 – 4 wks)
Neural tube
àBrain & Prosencephalic
Spinal cord Organization
(2 – 3 mos)
Neural crest (5 – postnatal years)
àPNS & Paired cerebral Neuronal
leptomeninges Hemispheres, Proliferation Synaptogenesis à Myelination
LV, BG, (3 – 4 mos) programmed (Birth – Postnatal yrs)
Thalami, Optic Full comple- Neuronal Cell death
Formation of myelin à
Nerves/ Ment of neu- electrical conduction
Migration
chiasm rons in
(3 – 5 mos)
CC, SP cerebral
hemispheres Formation from
4 layered embryonic
cortex à 6 layered
adult cortex
 Congenital Anomalies in the different stages
Of CNS development
Gestational Age in Months
Postnatal
1 2 3 4 5 6 7 8 9

Neurulation
(3 – 4 wks)
Encephalocoele
Prosencephalic
Myelomenin- Organization
(2 – 3 mos)
gocoele (5 – postnatal years)
Neuronal
Holoprosence- Perinatal Insults Myelination
Proliferation
phaly ICH/ HIE (Birth – Postnatal yrs)
(3 – 4 mos)
Dandy walker Tumors
Aqueductal Neuronal Perinatal Insults
Stenosis CNS Infections ICH
Migration
Hydroceph (3 – 5 mos) Tumors
CNS Infections
Schizencephaly
Colpocephaly
Lissencephaly
Agenesis of corpus callosum
CHECK VOLPE!
Neural Tube Defects (Posterior
Midline Defects/Dysraphism)

¨ Results from failure of the neural tube to

close spontaneously between the 3rd-4th
week of in utero development
¨ Possible etiologic factors:
– Radiation
– Drugs
– Malnutrition
– Chemicals
– Genetic determinants (mutations in folate-
responsive and folate-dependent pathways)
Neural Tube Defects
¨ Spina bifida occulta
¨ Meningocoele/ Myelomeningocoele
¨ Encephalocoele
¨ Anencephaly
¨ Dermal sinus
¨ Tethered cord
¨ Syringomyelia
¨ Diastematomyelia
Neural Tube Defects
¨ Diagnostic tool:
– Failure of closure of the neural tube allows
excretion of fetal substances (AFP,
acetylcholinesterase) into the amniotic fluid
– Prenatal screening of maternal serum for AFP
during 16-18 week AOG
– Rostral end of the NT closes on the 23rd day
and the caudal neuropore closes by the 27th day
of development
Neural Tube Defects and FA
¨ Maternal periconceptional use of folic acid
supplementation reduces the incidence of NT
defects by at least 50%
¨ US: recommends all women of childbearing age
take 0.4 mg of folic acid daily, and women with
previous pregnancy of NT defect should be treated
with 4 mg of folic acid beginning one month
before pregnancy is planned, until at least the 12th
week AOG when neurulation is complete
¨ Fortification of flour, pasta, rice and cornmeal
with 0.15 mg of folic acid/100 g was mandated in
the US and Canada in 1998
 S. N., 2 mos old, female

Marked obstructive Hydrocephalus

secondary to ARNOLD CHIARI II

Neurulation Period
Gestational Age in Months
Postnatal
1 2 3 4 5 6 7 8 9
Chiari Malformation

Type I Type II
Myelomeningocoele
¨ Most severe form of dysraphism involving the
vertebral column with an incidence of ~1/4000 LB
¨ Risk of recurrence after one affected child
increases to 3-4% and increases to ~10% with 2
previous abnormal pregnancies
¨ Certain drugs that antagonize folic acid (TMP,
AEDs: CBZ, PHY, Pb, primidone) increase the
risk of myelomeningocoele
¨ Valproic acid cause NT defects in ~1-2% of
pregnancies
Myelomeningocoele
¨ May be located anywhere along the neuraxis but
the LS region accounts for 75% of the cases
¨ Extent and degree of the neuro deficit depend on
the location
¨ CM: flaccid paralysis, absent DTRs, sensory
deficit below the affected level, postural abn of
the LE (clubfeet, subluxation of the hips), constant
urinary dribbling and a relaxed anal sphincter
Myelomeningocoele

¨ HCP in association with a type II Chiari defect

develops in at least 80% with myelomeningocoele
¨ Infants with HCP and Chiari II develop symptoms
of hindbrain dysfunction: difficulty feeding,
choking, stridor, apnea, VC paralysis, pooling of
secretions, spasticity of UEs
¨ Chiari crisis is due to downward herniation of the
medulla and cerebellar tonsils
Myelomeningocoele
¨ Requires a multidisciplinary approach: surgeon,
therapist, pediatrician
¨ Surgery: repair and shunting; orthopedic
procedure, urologic evaluation
¨ GUT: regular catheterization to prevent UTI and
reflux leading to PN and hydronephrosis, urine
cult, serum elec, creatinine, renal scan, IV
pyelogram, Utz
¨ Rehab: functional ambulation (sacral or LS lesion)
Myelomeningocoele
¨ Prognosis:
– MR- 10-15%
– Most deaths occur before age 4 years
– 70% have normal intelligence, but learning
problems and seizure disorders are common
– History of meningitis or ventriculitis adversely
affect the ultimate IQ
 11 mos old, male

Neurulation Period
Gestational Age in Months
Postnatal
1 2 3 4 5 6 7 8 9
Encephalocoele
¨ Cranium meningocoele: CSF-filled
meningeal sac only
¨ Cranial encephalocoele: contains the sac
plus cerebral cortex, cerebellum or portions
of the brainstem usually with abnormalities
¨ Usually occurs in the occipital region or
below the inion, although in some countries,
frontal or nasofrontal encephalocoeles are
more prominent
Encephalocoele
¨ Dxtic:
– Plain x-ray of the skull and cervical spine
– Cranial utz
– In utero: AFP, biparietal diameter
¨ Prognosis:
– Encephalocoele- at risk for visual problems,
microcephaly, MR, seizures
– Meckel-Gruber syndrome: AR condition,
occipital encephalocoele, cleft lip or palate,
microcephaly, microphthalmia, abnormal
genitalia, polycystic kidneys, and polydactyly
Hydrocephalus
¨ Obstructive HCP
– Aqueductal stenosis- x-linked recessive trait,
associated with spina bifida occulta, NF
– Aqueductal gliosis- 20 to neonatal meningitis or
SAH in PT, intrauterine viral infections,
mumps meningoencephalitis
– Vein of Galen malformation
– Space occupying lesions in the posterior fossa
 C. V., 1 month old
At 2 weeks of age was
noted to have a fast
enlarging head

Aqueductal Stenosis

Neuronal Proliferation
Gestational Age in Months
Postnatal
1 2 3 4 5 6 7 8 9
Hydrocephalus
¨ Infant: increasing HC, open and bulging AF,
dilated scalp veins, broad forehead, setting-sun
eye signs, hyperreflexia, spasticity, clonus,
bilateral Babinski sign
¨ Child: irritability, lethargy, poor appetite,
vomiting, headache. Gradual personality change
and deterioration in academic performance
¨ Serial HC monitoring, Macewen sign
¨ Papilledema
Hydrocephalus
¨ Cause: Dandy-Walker malformation- cystic
expansion of the 4th ventricle in the posterior fossa
¨ Dxtic:
– Plain skull x-ray: separation of sutures, erosion of the
post clinoids, beaten-silver appearance
– UTZ/CT/MRI
¨ DDx: thickened cranium, metabolic and
degenerative disorders producing megalencephaly,
gigantism, NF, familial megalencephaly
¨ Management: depends on the cause
Dandy Walker
Malformation

R.B, 2 months old

male, noted at birth
to have a big head

Prosencephalic Period
Gestational Age in Months
Postnatal
1 2 3 5
Cerebral Palsy
PEARL JOY L. SENDAYDIEGO
Pediatric Neurologist
Definition
¨ A group of disorders of movement and
posture
¨ Static encephalopathy, non-progressive
¨ Co-exists with sensory, behavioral,
cognitive manifestations
Clinical Manifestations
¨ Delay in developmental milestones
¨ Neurologic examination at intervals will
reveal no deterioration/loss of previously
acquired milestones
¨ Mild abnormalities may improve to normal
¨ Persistence of primitive reflexes
¨ Presence of pathologic reflexes
¨ Failure to develop protective reflexes
Etiology
¨ Three major syndromes
– Cerebral palsy that arises in infants of very
LBW
– Cerebral palsy in term infants who are
neurologically and systemically ill
– Cerebral palsy identified later in an apparently
healthy newborn
Etiology
¨ CP in LBW infants
– Commonly SGA
– Usually spastic diplegia
– Causes: asphyxia neonatorum, congenital
malformations, IVH
– Patho: white matter necrosis
– CP is higher in infants with BW <1500 gms.
Etiology
¨ CP in sick neonates
– CM: low APGAR, persisting hypotonia,
difficulty initiating and sustaining respiration,
early seizures, depressed reflexes, subnormal
LOC
– Causes: asphyxia, CNS infections, stroke,
congenital malformation, trauma
Etiology
¨ CP in well newborns
– Causes:
• Cortical dysgenesis 2° to abnormal neuronal
migration
• Hyperbilirubinemia
• Congenital infections: TORCH
• Subependymal and IVH
Classification
¨ Spastic CP
– Spastic quadriparesis
– Spastic diplegia
– Spastic hemiparesis
¨ Extrapyramidal CP
¨ Hypotonic CP
¨ Mixed and atypical forms
Spastic CP
¨ Most frequent type (50%)
¨ Diplegia is most common in SGAs and
twins
¨ Positive signs of hypertonia, hyperreflexia,
extensor plantar response, clonus
¨ Negative signs: slow effortful voluntary
movements, impaired line motor function,
difficulty in isolating individual movement
and agitability
EP (Dyskinetic) CP
¨ Account for 20% of CP
¨ Mainly dystonic, athetoid, choreic
– Athetoid: Facial grimacing with oropharyngeal
difficulties, fingers are extended and abducted when
reaching for objects
– Choreic: contraction of small muscle groups involving
the face, bulbar muscles and proximal part of the
extremities, hypotonia is prominent
– Dystonia: initially hypotonic, later becoming
hypertonic, DTRs are difficult to elicit, severe
dysarthria
Astatic/Hypotonic CP
¨ Seen in term infants
¨ May remain hypotonic for several months
¨ May never stand or walk
¨ Associated with microcephaly and profound
MR
Associated Problems
¨ Abnormalities in intellect, MR in 65%
¨ Learning disabilities
¨ Ocular, visual, hearing abnormalities
¨ Problems with attention, vigilance and behavior
¨ Language problems
¨ Abnormal speech may be due to problems of the
oropharynx and coordination of breathing patterns
Management

¨ Multidisciplinary
¨ Assessment of general health status,
nutrition
¨ Developmental assessment of function
¨ Assessment of pulmonary status
¨ Management of concomitant neurologic
problems
¨ Management of genitourinary problems
Thank You