Pediatric Neurology Notes

AAnotes

pediatric neurology resident's study notes

by: Abdelrahman

Alsherbini

AAnotes.net

Hi, My name is Abdelrahman Alsherbini. I'm a PGY-4 Pediatric Neurology resident .

I used to take notes while reading. I'm happy to share it with everyone.

Errors are expected to happen although efforts to avoid it.

Please feel free to contact me at aanotes.net@gmail.com

AAnotes.net

We are using color coding to tailor the topics discussed in each page according to the right audience groups as follows:

Green pages are mainly for medical students.
Brick-red pages are mainly for non-pediatric neurology residents.
Navy-blue pages are mainly for pediatric neurology residents.

Neonatal History

Birth history

Ex (--) wks
Vaginal delivery:

spontaneous vs forceps vs Vaccum.

C-Section: emergency or planned.
APGAR
Resuscitation
Cried immediately vs NICU admission
The prenatal US
Fetal kicks
Maternal illness
Maternal drug use

Other histories

Medical history: no history of febrile or afebrile seizure
Surgical history: denies
Family history: no family members with febrile or afebrile seizure or developmental delay
Social history: siblings developmenat
Allergy: denies any allergy to food or medications
Immunization: HBV vaccine at birth

Neonatal Physical exam

General

Respiratory status
Genetic facies (low set ears, hypertelorism, depressed nasal bridge).
Head circumference (percentile for conceptual age)
Anterior fontanel (size and fullness) mildly sunken while sitting
Sutures are appropriately aligned.
No hematoma
Birth marks (numbers and sizes)

Motor & Sensory:

Vertical suspension
Horizontal suspension
Looking for scissoring of LEs
Assess tone on passive movement
Symmetric movement of all extremities
Sensory: Ticklish to touch in all extremities

Cranial Nerves

II: Pupils reactive, red reflex
III: no ptosis
III, IV, VI: normal oculocephalic reflex (when turning head to one side, both eyes move to the opposite)
VII:

o Upper face: symmetric eye closure

o Lower face: symmetric mouth movement

Reflexes

Biceps, Knee, Ankles.
Palmar grasp (till 6 months)
Plantar grasp (till 15 months)
Galant reflex (till 4 months)
Asymmetric tonic neck (till 3 months): rotation of neck to one side results in extension of ipsilateral UE.
Crossed extensor reflex (till 6 weeks): Flexion on one LE, result in extension of the other LE.
Moro reflex (till age of 6 months).
Babinski sign: abnormal before 12 months.

Neonatal Seizures

approach

Mimics

• Benign nocturnal myoclonus

• Jitteriness

• Nonconvulsive apnea

• Normal movement

• Opisthotonos

• Pathological myoclonus

Workup

STAT LTRV looking for subclinical seizures.
Look for the primary cause.

Management

Phenobarbital.
Keppra.
Fosphenytoin.
Vimpat.

Long term management

Treatment of the primary cause.
Continue the antiseizure meds with least side effcts.

Neonatal Seizures

Mimics

Apneic spells

Look at the heart rate. If it's associated with bradycardia, then less likely to be a seizure.
Look at the muscle tone, if hypertonic or eye deviation associated with it, higher chances of seizures.
Persistent apnea and loss of consciousness, suggestive of ICH.

Jitteriness

Generalized shakiness in all extremities and jaw.
No change in respiration or eye movements.
Worse by stimulation such as tactile, auditory or motion.

Common presentations of neonatal seizures:

Apnea with tonic stiffening of body.
Focal or multifocal clonic movements of one or more limbs
Myoclonic jerking
Paroxysmal laughing
Tonic deviation of the eyes

Benign Nocturnal Myoclonus

Shakiness of fingesrs, wrists and elbows.
Occurs exclusively during sleep.
Stops by holding the baby's extremities or awakening.

Hyperekplexia

Exaggerated startle reflex and hypertonia as a response to tactile or auditory stimuli.
Maybe associated with seizures, apnea and developmental problems.
Maybe genetic or non genetic.
TTT: Clonazepam

Neonatal Seizures

treatment

Phenobarbital

Load: 20 mg/kg one time only.
Maintain: 5 mg/kg/day divided BID.
Send troph level before the next dose. Therapeutic: 10-40.
If troph level > 40, hold the next dose for concern of apenia.

Fosphenytoin

Load: 20 mg/kg
Maintain: 10 mg/kg/day q12H
Send troph level before the next dose.
Therapeutic: total 20, free 2

Oxcarbazapine

Better if the patient has a focal source of seizures.
Loading dose 40 mg/kg
Maintain: 40 mg/kg/day divided BID.

Keppra

Load: 40 mg/kg one time only.
Maintain: 40-60 mg/kg/day divided BID.
No troph level needed.

Vimpat

Make sure the patient has no history of cardiac disease.
Loading dose 10 mg/kg
Maintain: 5 mg/kg/day divided BID.

Neonatal Seizures

work-up

Metabolic

CMP, Mg, Phos.
Billirubin; total & direct.
TSH, fT4.
Ammonia.
ABG: ionized Ca & lactate.
Serum Amino Acids.
Urine Organic Acids.
Serum Acylcarnitine profile.

Structural

Head US.
Head CT vs MRI w/o
Brain MRV w/o

Infectious

CBC with diff.
Blood culture.
Serum HSV PCR.
Urinalysis, Urine culture.
CSF glucose, protein, lactate, culture, HSV PCR.

Benign Familial Neonatal Seizures

multifocal brief motor seizures
Otherwise normal function.
Look for a family history of similar events
Oxcarbazapine is the treatment of choice.
Start with 20 mg/kg/day then double later.

Neonatal Seizures

Based on age of Onset

0-12 hours

HIE.
Premature newborns: intraventricular hemorrhage.
Large full-term newborns: SAH or cerebral contusion.
All gestational ages: sepsis, meningitis, cerebral dysgenesis, direct drug effect.
Folate or Vit B6 dependant seizure.

After 72 hours

Typical period for inborn error of metabolism. Look for history of poor feeding and hypotonia.

24-72 hours

As above.
Idiopathic cerebral venous thrombosis.
Congenital hypocalcemia.
Glycogen, glycine, Urea cycle disorders.
Tuberous Sclerosis.

After a week

Adrenoleukodystrophy.
Non ketotic hyper glycenemia.
Fructose.
Gusher gangliosidosis
Maple syrup urine.

Neonatal Seizures

lab results

Hyperammonemia

Argininosuccinic acidemia Carbamylphosphate synthetase deficiency.
Citrullinemia
Methyl malonic acidemia
Multiple carboxylase deficiency.
Ornithine transcarbamylase (OTC) deficiency.
Propionic acidemia.

Metabolic acidosis

Glycogen storage disease type1.
Fructose 1,6-diphosphatase deficiency
Multiple carboxylase deficiency.
Maple syrup urine disease
Methyl malonic acidemia.
Propionic acidemia

High lactate

Glycogen storage disease type1.
Fructose 1,6-diphosphatase deficiency
Multiple carboxylase deficiency.
Mitochondrial disorders.

Hypoglycemia

Glycogen storage disease type1.
Fructose 1,6-diphosphatase deficiency
Maple syrup urine

Hypoxic Ischemic Encephalopathy

Diagnosis

Any patient with gestational age ≥ 35weeks who meets any of the following criteria:

APGAR Score

Apgar score of <5 at 5 minutes and 10 minutes

Cord Blood Gases

Fetal umbilical artery pH <7.0, or base deficit ≥12 mmol/L, or both

Multisystem Organ Failure

Presence of multisystem organ failure consistent with hypoxic-ischemic encephalopathy (HIE)

MRI

Brain MRI shows brain injury secondary to hypoxia-ischemia, including deep nuclear gray matter or watershed (border zone)

Infants

(28 days-12 months)

History

Birth History

Ex (--) wks
Vaginal delivery:
spontaneous vs forceps vs Vaccum.
C-Section: emergency or planned.
APGAR
Resuscitation
Cried immediately vs NICU admission

Other Histories

Medical history: no history of febrile or afebrile seizure
Surgical history: denies
Family history: no family members with febrile or afebrile seizure or developmental delay
Social history: daycare
Allergy: denies any allergy to food or medications
Immunization: UTD per mom

Developmental History

Gross motor.
Fine motor.
Social.
Speech.

Developmental

Mile stones

2 months

4 months

6 months

45 degree

Head

Support

Full Head

Support

Sitting

Supported

Switch toy

between hands

Reachout

to toy

Brings toys

to mouth

Single

Sallyble

Cooing

Squealing

Smiles

spontenously

Recognize

familiar faces

Stranger

Anxiety

Developmental

Mile stones

18 months

10 months

12 months

Pull to stand

Cruising

Walk

with support

Walk

without support

Pincer grasp

(finger food)

Building

2 block Tower

Pointing

Double

sallyble

Says Mama/Dada

to right person

3-5 words

Playing

Peek-A-Boo

Responds to

their names

Shows affections

Developmental

Mile stones

2 Years

3 Years

4 Year

Stands on a foot

for 5 secs

Running

Uses Stairs

Copy

straight line

Copy circle

Catches large ball

Two-word

sentence

Say their names

Complete sentences

understands facial expressions

Take turns

Follows rules

Shared playing

BRUE

Definition

Breif

Less than one minute.

Resolved

The patient is back to their baseline after then event.

Unexplained Event

There is no clear cause for the event by history and physical exam.

Breathing.
Responsiveness.
Uncolored.
Extremities tone.

Associated with changes one or more of:

BRUE

Classification

Low Risk BRUE

Post conceptual age >45 weeks
First time BRUE.
Duration < 1 minute
No CPR was done by EMS
No concerns by history and exam

Concerning history

Concerns for child abuse.
Recent respiratory illness.
Recent injury.
Recurrent vomiting.
Developmental delay.
H/O death in a sibling.
H/O congenital anomalies.
Prolonged generalized cyanosis.

Concerning physical exam

Signs of bleeding, and bruising.
Bulging anterior fontanel
Altered mental status.
Fever or toxic appearance.
Respiratory distress.
Heart murmur or gallop.
Hepatomegaly or splenomegaly.
Abdominal distension or vomiting.

BRUE

Management

Low Risk BRUE

Counselling
Offer resources for training for CPR.
Follow-up with PCP within 24 hours.
One to four hours observation with continuous pulse oximetry.
ECG: 12-lead with attention to QT interval.
The AAP guideline specifically recommends against evaluating for systemic infection

Consider EEG

Recurrent episodes of loss tone of muscles with the unresponsiveness.
The episodes aren’t associated with chocking or gagging.
Suspected non accidental trauma.

Differential Diagnosis

Toxic appearance: infectious workup
Altered mentation: toxic & metabolic workup.
Gross emesis or oral reguitation: GERD.
Cyanosis or abnormal ECG, cardiac reasons.

High Risk BRUE

Pulse oximetry monitoring for at least four hours
Electrocardiogram
CBC with Diff (Hematocrit).
Blood glucose
Venous blood gas, lactic acid (to evaluate for inborn errors of metabolism).
Respiratory virus testing panel.

Febrile seizures

Diagnosis

Criteria

Age: 6 months to 6 years
Fever within 24 hours of the seizure. Before or after it.
No history of afebrile seizure
No signs of CNS infection
No signs of acute metabolic derangements.

When to suspect CNS infection rathar than FS?

Prolonged postictal state
Altered mentation before the seizure
Age less than one year old with missed vaccination

Classification

Complex febrile seizure if one of the:

Frequency: complex if > once in 24 hours
Focally: complex if focal onset
Duration: complex if > 15 mins

Febrile status epilepticus:

Febrile seizure > 30 mins

Red flags

Family history of afebrile seizures.
Significant developmental delay.
History of recent vaccination.

Febrile seizures

Differential

Diagnosis

Febrile Seizures Plus

Age range outside typical febrile seizures (before 6 mo or after 6 yo)
Or both febrile & afebrile GTC seizures

Generalized Epilepsy with Febrile Seizures Plus

• Genetic: runs in families

• Epilepsy: different phenotypes within

the family members

• With Febrile Seizures Plus: it may range from FS to FS+

Dravet Syndrome

aka sever myoclonic epilepsy of infancy.

Generalized clonic or hemiclonic seizures.
Exacerbated by fever, illness or vaccinations.
Normal development before the seizure. Followed by regression.

Febrile Illness with Refractory Epilepsy

Normal child developmentally before the seizure
Febrile seizure
Followed by refractory status epilepticus
early start for autism

Febrile seizures

Management

For all seizures

Airway.
Breathing.
Circulation.
Timing.
If seizure > 3 mins:

IV: Ativan 0.1 mg/kg, Diastat 0.2mg/kg

IM: Diastat 0.2 mg/kg

Rectal: Diastat 0.2 mg/kg

When discharged, offer rectal diastat 0.5 mg/kg for seizures > 5 mins.

Complex ferile seizures

The decision about the workup depends on the case-by-case discussion.
Offer Diastat as a rescue medication.

Febrile Status Epilepticus

Any febrile seizure longer than 30 minutes.
It increases the risk for epilepsy byucausing hippocampal sclerosis.

Simple febrile seizures

Reassurance.
No need for workup or followup.

Febrile seizures

Differential

Diagnosis

Febrile Seizures Plus

Age range outside typical febrile seizures (before 6 mo or after 6 yo)
Or both febrile & afebrile GTC seizures

Generalized Epilepsy with Febrile Seizures Plus

• Genetic: runs in families

• Epilepsy: different phenotypes within

the family members

• With Febrile Seizures Plus: it may range from FS to FS+

Dravet Syndrome

aka sever myoclonic epilepsy of infancy.

Generalized clonic or hemiclonic seizures.
Exacerbated by fever, illness or vaccinations.
Normal development before the seizure. Followed by regression.

Febrile Illness with Refractory Epilepsy

Normal child developmentally before the seizure
Febrile seizure
Followed by refractory status epilepticus
early start for autism

Upper extremities muscle groups

Elbow Extensors

Triceps (R. N.)
Anaconeus (R. N.)

Shoulder Adductors

Pectoralis Major ( Lateral & medial pectoral nerves C5-T1).
Teres major (Sub-scapular N. C5-6)
Latissmus dorsi (Sub-scapular C6-8)
Triceps (R. N.)
Coraco-Brachialis (Musclo-Skeletal)

Shoulder Abductors

0-15 degrees: Supraspinatus (Suprascapular N.)
15-90 degrees: Deltoid (Ax. N.)
> 90 degrees:

Trapezius (Cranial Nerve XI)
Serratus anterior (long thx N.)

Elbow Flexors

Biceps. (Musclo-Cut.)
Brachialis. (Musclo-Cut.)
Brachi-radialis. (Radial N.)

Hand Grip

Palmar interossi. (Ulnar n.)
Adductor pollicis. (Ulnar n.)
Opponence pollicis. (Ulnar n.)
Opponence digiti-minimi (Ul. n.)
Flexor pollicis longus. ( M. )
Flexor pollicis brevis. (M.)
Flexor digitorum superfacialis. (M.)
Flexor digitorum profundus. (Ul & M)
Flexor digiti-minimi. (Ul. N)

Neuromuscular Physical exam

Muscle Strength

0: No muscle movement.
1: Muscle twitching.
2: Incomplete range of motion anti-gravity.
3: Full anti-gravity range of motion.
4: Full range of motion against some resistance.
5: Full range of motion against examiner’s full resistance.

Deep Tendon Reflexes

0: absent.
1: hyporeflexic.
2: normal.
3: hyperreflexic.
4: unsustained clonus.
5: sustained clonus.

Mucle Bulk

By palpation of the muscle.
Can be categorized into:

Atrophy.
Normal.
Hypertrophy.

Muscle Tone

Hypotonia: anterior horn cells or cerbellar lesions.
Normotonia
Rigidity: basal ganglia lesions.
Spasticity: cortico-spinal tract lesions.

upper extremities Main nerve supply

Radial N. (C5,6,7,8):

Abductor Pollicis Longus
Supinator
Brachio-radialis
Extensors:

Pollicis longus
Pollicis brevis
Digitorum superfacialis
Digitorum profundus
Carpi radialis
Carpi ulnaris

Abductor Pollicis Brevis
Lumbricles 1 & 2
Pronators (teres & quad)
Flexors:

Pollicis longus
Pollicis brevis
Digitorum superfacialis
Digitorum profundus: Radial part
Carpi radialis

Median N. (C5,6,7,8 & T1)

Musclo-cutenous N. (C5,6,7)

Biceps.
Brachialis.
Coraco-Brachialis.

Ulnar N, (C8-T1)

Opponence pollicis
Lumbricles 3 & 4
Interossei
Adductor pollicis
Flexor Carpi Ulnaris
Ulnar half of Flexor Digitorum Profundus

lower extremities muscle groups

Hip Flexors: (Psoas major & Femoral N.)

Psoas major ( L1-4)
Pectinius. (Femoral N.)
Iliacus (Femoral N.)
Sartorius (Femoral N.)
Quadriceps (Femoral N.)

Knee Flexors:

Hamstrings (Tibial N.)
Gracilis (Obturator N.)
Gastrocnemius (Tibial N.)
Sartorius (Femoral N.)
Popletius (Tibial N.)

Hip Abductors (Superior Gluteal N. L4,5 & S1)

Gluteus medius.
Gluteus minimus.
Tensor fascia lata.

Hip Extensors: (Gluteus max & hams)

Gluteus Maximus (Inferior Gluteal Nerve L5, S1, S2)
Hamstrings (Tibial N. L4,5, S1,2,3)

Semi-tendenious.
Semi-membranous.
Biceps femoris

Hip Adductors: Obturator Nerve L2,3,4:

Adductor longus.
Adductor brevis.
Adductor magnus.
Gracilis.
Pectinius.
Obturator externus.

lower extremities muscle groups

Femoral N. (L2,3,4)

Iliacus
Pectineus
Sartorius
Rectus femoris.
3 x Vastus (medialis, lateralis & intermedius)

Obturator Nerve L2,3,4:

Adductor longus.
Adductor brevis.
Adductor magnus.
Gracilis.
Pectinius.
Obturator externus.

Sciatic N.

(L4,5 & S1,2,3)

Tibial N. (Same as Sciatic)
Common Peroneal N. (L4,5 & S1,2):

Superficial peroneal
Deep peroneal

Lumbar Plexus (T12 : L4)

Iliohypogastric (L1)
Ilioinguinal (L1)
Genitofemoral (L1 & 2)
Lateral Femoral Cutaneous (L2 + L3)
Femoral (L2, L3, L4)
Obturator (L2, L3, L4)
Accessory Obturator (L3, L4)

Sacral Plexus (L5 : S5)

Superior gluteal N. (L4,5 & S1_
Inferior gluteal N. (L5, S1 &2)
Sciatic N. (L4,5 & S1,2,3)

lower extremities muscle groups

Ankle Dorsi Flexors

(Deep Peroneal N.)

Tibialis anterior.
Extensor hallucis longus.
Extensor digitorum longus.

Foot Eversion:

(Superfacial peroneal N.)

Fibularis longus.
Fibularis brevis.

Ankle Planter Flexors:

(Tibial N.)

Gastrconmius.
Soleus.
Plantaris.
Fibularis longus.

Foot Inversion

Tibialis anterior (Deep Peroneal N.)
Tibialis posterior (Tibial N.)

COMMON Outpatient CONCERNS

Behavior Concerns

Autism Spectrum Disorder.
Aggressive behavior.
ADHD.
Cognitive Impairment.
Learning Disability.

Headaches

Migraine with aura.
Migraine without aura.
Tension headaches.
IIH.
Cyclic Vomiting Syndrome.

Neuromuscular

Duchene Muscular Dystrophy.
Charcot Marie Tooth.
Cerebral Palsy.
Spinal Muscular Atrophy.

Concussion

Traumatic brain injury.
Post-concussion syndrome.

https://www.cerebralpalsyguide.com/cerebral-palsy/coexisting-conditions/

ADHD

Diagnosis

Symptoms in more than one

setting (eg, school and home)

Persist for at least six months
Started before 12 years old
Impair function in academics,

social and occupational activities

Be excessive for the

developmental level of the child

Inattention Symptoms

Failure to obtain attention to details.
Difficulty maintaining attention.
Easily distractable.
Avoids tasks that requires sustained mental efforts.
Doesn’t seem to listen when spoken to directly.
Doesn’t follow through instructions.
Difficulty organizing tasks.
Increase forgetfulness.
Often loses necessary things.

Hyperactivity Symptoms

Management

Pre-school age (4-5 years):

Start by behavioral therapy

(Parent Training in Behavior Management).

If failed, add Methylphenidate.

School age (> 5 years):

Start by Stimulants w/w/o

behavioral therapy.

Difficulty remaining seated.
Fidget while seated.
Often runs in situations where its considered inappropriate.
Unable to play quietly.
Often on the go.
Often talks excessively.
Often interrupts.
Often blurt out an answer quickly.
Has trouble waiting turns.

Pharmacologic

treatment for ADHD

Methyl-Phenidate

aka, Concerta, Daytrana, Ritalin.
Syrup: Quillivant XR.
Start with 5 mg/day.
Weight < 25 Kg, increase by 2.5 mg every 3 days. Max: 35 mg/day
Weight > 25 Kg, increase by 5 mg every 3 days. Max: 60 mg/day

Dexmethyl-Phenidate

aka Focalin.
Lasts for 5-6 hours rather than 3-5 hrs
Start with 2.5 mg/day.
Increase by 2.5 mg every 3 days.
If switching from methylphenidate, half the dose of Focalin is enough.
MAximum dose is 20 mg/day.

Amphetamine

aka Evekeo
Lasts for 4-6 hours.
For age < 6 yo, Start with 2.5 mg/day, Increase by 2.5 every wk. Max 40 mg/day.
For age > 6 yo, Start with 5 mg/day, Increase by 5 every wk. Max 40 mg/day.

Amphetamine -

Dextro-Amphetamine

aka Adderall
For age < 6 yo, Start with 2.5 mg/day, Increase by 2.5 every wk. Max 40 mg/day.
For age > 6 yo, Start with 5 mg/day, Increase by 5 every wk. Max 40 mg/day.

Dextro-Amphetamine

aka Dexedrin or Zenzidi
Syrup: Pro-Centra.
For age < 6 yo, Start with 2.5 mg/day, Increase by 2.5 every wk. Max 20 mg/day.
For age > 6 yo, Start with 5 mg/day, Increase by 5 every wk. Max 40 mg/day.

Cyclic Vomiting Syndrome

Diagnostic Criteria

Sterotypical vomiting.
At least five episodes at anytime.
At least four vomiting per hour
At least one hour for each episode.
Inbetween episodes, the patient is

Back to baseline.

The vomiting is not attributable to other disorders

Stereotypical Vomiting

6 to 8 times/hour at peak, Mean duration 2 days and 12 cycle/year.
Vomitus often has bile and blood.
Migraine s/s in 1/3 of patients.
Use of hot-water showers or bathing to attenuate nausea.
Rapid drinking of fluids before onset of vomiting due to bitterness of bile.
Most episodes occur at night or early morning.

Treatment

Avoid triggers.
Fluid resuscitation.
Ondansteron: 0.3 mg/kg/dose, up to a maximum of 32 mg/day.
Foseprepatent.

Abortive Treatment

Sumtriptan.
Aprepatent:
Weight <15 kg, 80, 40, 40 mg/day orally on days 1, 2 & 3.
Weight 15 - 20 kg, oral 80 mg/day for three days.
>20 kg body weight, 125, 80 80 mg/day on days 1,2 & 3.

First time seizure

Epilepsy or Not?

Two unprovoked (or reflex) seizures >24 hours apart
One unprovoked seizure with a high probability of further seizures afterward
Diagnosis of an epilepsy syndrome

Semiology:

How did the seizure start?
Awareness.
Eyes.
Mouth.
Voice.
Extremities.
Synchrony.
Abortive medication.
Post-ictal?

Provoked or unprovoked?

Vascular (stroke, Hge)
Infection (CNS)
Trauma
Autoimmune (AE)
Metabolic (Glu, Na, Ca)
Ingestion (drugs)
Neoplasm (CNS)

Seizure or a mimic?

Further workup?

EEG
EMU
MRI brain w/o.
Epilepsy gene panel
Starting anti-seizure medication?
Prescribe rescue medication.
Prescribe Vitamin D.
Counselling.

Newly Diagnosed Epilepsy

Seizure Classification

(SEMIOLOGY)

Generalized onset.
Motor

Tonic
Tonic-clonic
Atonic
Myoclonic
Myoclonic-atonic
Epileptic spasm

Non-motor (absence)

Typical.
Atypical.
Myoclonic- abs
+Eyelid myoclonia

Focal onset.
Awareness.
Motor vs Non-motor.
Non-motor:

Autonomic.
Behavior arrest.
Cognitive
Emotional
Sensory

Epilepsy Syndrome (AGE OF ONSET+ SEMIOLOGY + EEG)

Neonatal onset
Childhood-onset.
Adolescent onset.
All ages.

Epilepsy Classification (SEMIOLOGY + EEG)

Generalized epilepsy.
Focal epilepsy.
Generalized & focal epilepsy.
Unknown (normal EEG)

Etiology

Structural.
Genetic.
Metabolic.
Immune.
Infectious.
Unknown.

Safety Profile of Broad Spectrum

Anti-Seizure Medications

Onfi (Clobazam)

Clonazepam (Klonopin)

Keppra (Leviteracitam)

Briviact (Briviacetam)

S/E: Somnolence, ataxia, dizziness & behavioral symptoms.
Briviact has less common behavioral side effects.
No labs needed.

S/E: SJS, TEN, Anterograde amnesia, Sleepiness, Ataxia, aggressive outbursts, hyperactivity, insomnia, depression & suicidal ideation.
Routine labs: Liver enzymes, CBC w diff.

Depakote (Valproate)

Lamictal (Lamotrigine)

Slow titration every two weeks.
S/E: SJS, TEN, DRESS, Aseptic meningitis, Agranulocytosis, Neutropenia, Pancytopenia, and Pure red cell aplasia, Aplastic anemia, HLH.
Routine labs: CBC w diff, CMP, Serum levels of lamotrigine. It’s an enzyme inducer. So, check other ASM interacts with it.
Serum theraputic level is 3-15. Toxicity level > 20.

Don’t start in age < 5 years old for concern of hepatic failure specially in Alpert Huttenlocher Syndrome.
Avoid in female for hisutism and weight gain.
S/E: SJS, TEN, Weight gain, Alopecia, Hirsutism, Pancreatitis,, Liver failure, Hyperammonemia, Nervousness, insomnia, Photosensitivity, Tremor, Dizziness, Abdominal pain, Diplopia, Delirium, Hallucinations, Parkinsonism and Cognitive dysfunction, Nausea, Vomiting, Somnolence, Thromocytopnia, Red cell aplesia.
Routine labs: Liver enzymes, CBC w diff, Ammonia, Amylase, Lipase, Carnitine, total and free serum levels of valproate.

Topamax (Topiramate)

Fycompa (Perampanel)

S/E: Dizziness, vertigo, hostility, suicidal, homicidal ideation, aggressive behavior, drowsiness, and abnormal gait.

S/E: SJS, TEN, Renal stones, Hyperammonemia, Pancreatitis, Tingling, Weight loss, Suicidal ideation, Hyperchloremic metabolic acidosis, aggressive behavior, mood disorder, drowsiness, fatigue.
Routine labs: CMP, Ammonia, GGT, Amylase, Lipase.
It’s an enzyme inhibitor. So, check serum levels of other ASM interacts with it.

Epidiulox (Cannabidiol)

S/E: Anemia, Hepatotoxicity, Weight loss, Skin rash, Decreased appetite, Diarrhea, Vomiting, Diarrhea, Drowisness, Insomnia.
Routine labs: CBC w diff, ALT, AST, Billirubin and serum level of Canabidol.

Side effects; Dizziness, somnolence, anorexia, ataxia, fatigue, abnormal thinking, confusion and renal stones.

Rufinamide

S/E: shortened QT interval, Nausea, vomiting, Dizziness and fatigue.

Zonisamide

Broad Spectrum

Anti-Seizure Medications

SV2A blocker

Keppra (Leviteracitam)

Starting dose

Peds: 20 mg/kg/day

Adults: 500 mg/day

Titration

Every week by

10 mg/kg/day

Peds: 60 mg/kg/day

Adults: 4000 mg/day

Maximum dose

SV2A blocker

Briviact (Briviacetam)

Peds: 1 mg/kg/day

Adults: 50 mg/day

Starting dose

Titration

Every week by

0.5 mg/kg/day

200 mg/day in both peds and adults

Maximum dose

GABA-A Blocker

Onfi (Clobazam)

Peds: 0.5 mg/kg/day

Adults: 10 mg/day

Starting dose

Titration

Every week by

0.5 mg/kg/day

Peds: 1 mg/kg/day

OR 20 mg/day

Adults: 40 mg/day

Maximum dose

Broad Spectrum

Anti-Seizure Medications

Block GABA Transaminase

Depakote (Valproate)

Starting dose

Peds: 15 mg/kg/day

Adults: 1000 mg/day

Titration

Q week 10 mg/kg/day

Goal 30 mg/kg/day

Maximum dose

Peds: 60 mg/kg/day

Adults: 2000 mg/day

Rufinamide

Unknown MOA

Use 1/2 the doses W Valproate

Peds: 10 mg/kg/day

Adults: 400 mg/day

Starting dose

Titration

Every other day by

10 mg/kg/day

Maximum dose

Peds: 45 mg/kg/day

Adults: 3200 mg/day

Voltage Gated Na Ch

Use x2 the doses W Valproate

Lamictal

Peds: 0.3 mg/kg/day

Adults: 25 mg/day

Starting dose

Titration

First two wks: double

Every two weeks by

0.6 mg/kg/day till goal 4.5

Maximum dose

Peds: 300 mg/day

Adults: 400 mg/day

Broad Spectrum

Anti-Seizure Medications

Block AMPA channels

Fycompa (Perampanel)

Peds & adults:

2 mg/day

Starting dose

Titration

Every week by 2 mg/d

Goal 4 mg/d.

Peds & adults: 8 mg/day.

Maximum dose

Unknown MOA

Zonisamide

Peds: 1 mg/kg/day

Adults: 400 mg/day

Starting dose

Titration

Q week 2 mg/kg/day

Goal 4 mg/kg/day

Maximum dose

Peds: 12 mg/kg/day

Adults: 600 mg/day

Block AMPA channels

Topamax

Block AMPA channels

Epidiulox (Cannabidiol)

Peds: 3 mg/kg/day

Adults: 25 mg/day

Starting dose

Pediatric & adult dose: start by 5 mg/kg/day

Starting dose

Titration

Q week 3 mg/kg/day

Goal 6 mg/kg/day

Maximum dose

Peds: 9 mg/kg/day

Adults: 400 mg/day

Q week 5 mg/kg/day

Goal 10 mg/kg/day

Titration

20 mg/kg/day

Maximum dose

Safety Profile of Narrow Spectrum

Anti-Seizure Medications

Oxcarbazapine (Trileptal)

Carbamazapine (Tegretol)

Monitoring labs: CMP, CBC w diff, serum level of other ASDs. liver function (AST, ALT, Alkaline Phosphatase, GGT), Lipid panel, serum carbamazepine levels, thyroid function tests; pregnancy test

S/E: SJS, TEN, DRESS, aplastic anemia or defect in any blood cell count, hyponatremia, attaxia, suicidal ideation, speech disturbance, drowsiness, fatigue.
Remember: enzyme inducers (Phenytoin, Phenobarb, Lamotrigin & Carbamazapines)
Monitoring labs: serum Na, CBC w diff, serum level of other ASDs.

Fycompa (Perampanel)

Lacosamide (Vimpat)

Cardiac arrhythmias including, but not limited to bradycardia, atrioventricular block, and tachyarrhythmias such as atrial fibrillation, atrial flutter, and ventricular tachycardia.
SJS, TEN, DRESS.
Monitoring: ECG tracing prior to start of therapy and when at steady-state.

S/E: SJS, TEN, DRESS, Cardiac arrhythmia, liver failure, aplastic anemia or defect in any blood cell count, hyponatremia, attaxia, suicidal ideation, speech disturbance, drowsiness, fatigue.
Remember: enzyme inducers (Phenytoin, Phenobarb, Lamotrigin & Carbamazepines)
Monitoring labs: CBC, comprehensive metabolic profile, liver function; 25-hydroxyvitamin D level

Narrow Spectrum

Anti-Seizure Medications

Trileptal (Oxcarbazapine)

Na channel blocker

Peds: 8-10 mg/kg/day

Adults: 300 mg/day

Starting dose

Titration

Every week by 5-10 mg/kg/d

Goal 30 mg/kg/d.

Peds: 60 mg/kg/day.

Adults: 2400 mg/day

Maximum dose

Tegretol

(Carbamazepine)

Na channel blocker

Peds: 10 mg/kg/day

Adults: 200 mg/day

Starting dose

Q week 100 mg/day

Titration

Maximum dose

Peds: 35 mg/kg/day

Adults: 800 mg/day

Na channel blocker

Phenytoin

Na channel blocker

Lacosamide (Vimpat)

Peds: 5 mg/kg/day

Adults: 200 mg/day

Starting dose

Peds: 2 mg/kg/d

Adults: 100 mg/day

Starting dose

Titrated based on serum levels and clinical response

Titration

Q week 2 mg/kg/d

Goal 4 mg/kg/day

Titration

Maximum dose

Peds: 10 mg/kg/day

Adults: 400 mg/day

Peds: 8 mg/kg/day

Adults: 600 mg/day

Maximum dose

Neonatal Epilepsy Syndromes

SELF-LIMITED NEONATAL SEIZURES

SELF-LIMITED FAMILIAL NEONATAL EPILEPSY

Onset: 4 and 7 days

Remission: 4-6 months

Onset: second month of life

Remission: 4-6 months

Hemi-clonic

Tonic, autonomic or vocal

Hemi-clonic

Tonic, autonomic or vocal

A theta pointu alternant pattern consists of runs of theta activity intermixed with sharp waves

Autosomal Dominant

Mainly: KCNQ-2

Autosomal Dominant

Mainly: KCNQ-2

MYOCLONIC EPILEPSY IN INFANCY

Onset: 6 mo - 2 yo

Remission: 5 yo

If seizure not control, cognitive difficulties

MUST have myoclonic seizures

May have febrile seizures

Later in life GTC

Normal EEG

No interictal discharges

Photic stim: activate Sz

Sz: generalized spike & wave

Unknown

Epileptic Encephalopathies

with Neonatal & Infantile Onset

EARLY MYOCLONIC ENCEPHALOPATHY

Onset: first two months

Poor prognosis

Fragmentary erratic myoclonus: migrating, asymmetric & asynchronus

High voltage bursts (150-300uV) of spikes or sharp and slow waves, are seen with inter-burst intervals

Metabolic

Structural

Genetic (ERb B4)

Ohtahara Syndrome

(Early infantile epileptic encephalopathy, EIEE

Onset: first three months

Poor prognosis

Forward tonic flexion that mey be symmetric or asymmetric

Same as EARLY MYOCLONIC ENCEPHALOPATHY

Structural or metabolic

Genetic (STXBP1, SLC25A22, CDKL5, PCDH19, KCNQ2, SCN2A)

West Syndrome

Dravet Syndrome (Sever Myoclonic Epilepsy of Infancy, SMEI)

Onset: 3-12 months

Poor prognosis

Onset: < 15 months

Poor prognosis

MUST have epileptic spasms

febrile, afebrile, hemiclonic 1-4 yo: myoclonic and atypical absence seizures

Hypsarrhythmia: high voltage irregular slow waves with multifocal spikes and polyspikes

1st year: focal slowing

2nd-5th year: generalized spike-and-wave & multifocal inter-ictal

Genetic SCN1A or PCDH19

Structural or metabolic

Genetic ARX, CDKL5, SPTA N1, STXBP1, T21, and Miller-Dieker

Epileptic Encephalopathies

with Neonatal & Infantile Onset

EPILEPSY WITH MYOCLONIC-ATONIC SEIZURES

(Doose Syndrome)

Onset: 6 mo to 6 yo

Followed by : decline in cognitive, behavioral and psychiatric functioning

MUST have Myoclonic-Atonic

MUST NOT be infantile spasm or focal seizure

Background: Bi-parietal Theta

Photic stim: cause spike & wave discharges

MUST exclude glucose transporter disorder

Maybe SCN1A & SCN2A

EPILEPSY OF INFANCY WITH MIGRATING FOCAL SEIZURES

Onset: 3-12 months old

Course: microcephaly in 1 yo

Sever cognitive impairment

MUST have migration of focal seizures in randomly order within the same seizure

multiple independent cortical regions randomly but consecutively in the same single seizure

Genetic as in ( in KCNT1, SCN1A, SCN2A, PLCB1, TBC1D24 and CHD2)

MYOCLONIC ENCEPHALOPATHY IN NON-PROGRESSIVE DISORDERS

Onset: Day 1 to age 5 years

Poor prognosis

MUST have Myoclonic status epilepticus (may last days-weeks)

Background: slow (theta-delta)

on central or parito-occipital

Eye closed: Spikes appear on slow activities.

Deep sleep: less spikes

Chromosomal 50% of cases

(as Angelman, Prader-Willi and Wolf Hirschorn syndromes,

Structural, metabolic

Epileptic Encephalopathies with Childhood Onset

Epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS)

Onset: 2-12 years old

progressive decline in cognitive, behavioral and psychiatric functioning

Asymptomatic

Continuous, fragmented or focal (frontal)

spike & wave1.5-2 Hz

is seen in slow sleep stage

Structural in 33%

Genetic (e.g Rett or GRIN2A)

Metabolic (mitochondrial)

Landau-Kleffner syndrome (LKS)

Lennox-Gastaut syndrome (LGS)

Onset: 2-8 years old

Residual language impairment in 80%

Onset: 1-7 years

Poor prognosis

Focal, atypical or atonic

NEVER GTC

Multiple seizure semiologies

Cognitive impairment

Spike & wave (<2.5 Hz)

High amplitude tempto-parietal spikes are seen in sleep

Background: abnormal

HV: < 2.5 Hz SW

Photic stim: Myoclonic-atonic

Sleep: paroxysmal fast > Hz

Genetic as in (GRIN2A)

Structural in 75%

Genetic (maybe De Novo)

Secondary to refractory epilepsy

Status EPilepticus

> 3-5 minutes

1-3 minutes

·Document the time of seizure start
·Lay the patient on their side to avoid aspiration
·Connect a pulseox. Oxygenate accordingly

If the patient has IV line:

Ativan: 0.1 mg/kg (max 4 mg)
Diastat: 0.2 mg/kg (max 10 mg)

If the patient doesn't have an IV line:

IM Versed (Midazolam) doses by weight:
If weight < 13 Kg, no evidence for using
If weight 13-40 Kg, 5 mg/dose
If weight >40 Kg, 10 mg/dose
Rectal Diastat 0.2 mg/kg (max 20 mg)
Nasal Versed 0.3 mg/kg (max 20 mg)

5-15 minutes

Levetricetam 60 mg/kg

Max 4500 mg/day

Fosphenytoin 20 mg/kg.

Max 1500 mg/day
Avoid if:
Known sodium channel mutation
or is already on phenytoin & no level.

Valproate 40 mg/kg

Max 3000 mg/day

Avoid if:

Younger than three years old.

End stage liver disease

Already on Valproate & has no level.

Refractory Status Epilepticus

If seizure didn't respond to one Benzo & one ASD

·Intubate.
·Load with another anti-seizure medication different from the previous step.
Order LTRV

After the second use of ASD

Start the drip:
Versed: 0.2 mg/kg bolus then 0.1 mg/kg/hr
Pentobarb: 5 mg/kg then 0.5 mg/kg/hr
Ketamine 1.5 mg/kg then 1 mg/kg/hr
Propofol 0.2 mg/kg then 0.2 mg/kg/hr
Phenobarb 20 mg/kg (max 100 mg/min)

Bolus: 5 mg/kg over 30 min.
Initial rate: 1 mg/kg/hr
Repeat bolus 5 mg/kg every 12 hours
After each bolus, increase rate by 0.5 to 1 mg/kg/hour
Max dose: 3 mg/kg/hr

Loading dose: 1.5 mg/kg
Initial rate: 1 mg/kg/hr
Repeat bolus every 5 minutes.
Then increase the infusion rate by 0.5 mg/kg/hr after every bolus.
Maximum infusion rate is 15 mg/kg/hr

Versed drip

Pentobarb drip

Ketamine drip

Bolus: 0.2 mg/kg
Initial rate: 0.1 mg/kg/hr
Repeat bolus Q5-15 min
After each bolus increase rate by 0.05 mg/kg/hr
Max dose: 1 mg/kg/hr

Approach to Identifying Cerebral Cisterns

Superior to Foramen Magnum

Cisterna Magna

Cerebello

Medullary

cistern

Sphenoid Bone

Start looking for the Pons

Superior to Foramen Magnum

Start looking for the medulla

Pre-Medullary Cistern

Sphenoid Bone

Start looking for the Pons

Pre-pontine Cistern

4th vent only with

Pones or upper medulla

4th ventricle

Just above the Clivus

Look for Suprasellar cistern

supra sellar

cistern

The highest level of the Petros Bone

Look for midbrain

The highest level of the Petros Bone

Look for midbrain

Inter-peduncular

cistern

Side Note

Anatomy of Midbrain

Anterior Horn of Lateral Ventricles

Look for the superior colliculi

Quadrigeminal cistern

Anterior Horn of Lateral Ventricles

Look for the superior colliculi

Reading EEG

Background

Awake vs. drowsy vs. asleep
Sleep staging
Background variants:

Rhythmic mid-temporal theta of drowsiness
Hypnopompic hypersynchrony
Hypnagogic hypersynchrony
Posterior slow waves of youth
Slow alpha variant
Frontal arousal rhvthm
Increased frontal beta activity
Fast alpha variant
Midline central theta (Ciganek rhythm)

Non Epileptiform Discharges

Wickets
Hyperventilation-induced slowing
Small sharp spikes
Mu rhythm
Photomyogenic response
Lambda waves
6 Hz phantom spikes
14-and-6 Hz positive spikes
Subclinical rhythmic electrographic
discharges in adults
Occipital needle-like spikes of blindness
Slow fused transient
Fronto-central (texting) rhythm

Artifacts

Eye blinking
Eye movements
EKG artifact
Pulse artifact
Electrode pop
Myogenic artifact
Glossokinetic
Chewing artifact
Sweat artifact

EEG background

Amplitude

+/- A-P Gradient

Normal > 20 uV
Low voltage 10-20 uV
Suppressed < 10 uV

A-P Gradient

Present
Reversed
Absent

Frequency

Delta (0.5-3.5)
Theta (> 3.5-<8)
Alpha (8-13)
Beta >13

Symmetry

In frequency:

Symmetric.

Mild asymmetry: 0.5-1 Hz

Marked asymmetry: > 1 Hz

In amplitude:

Symmetric.

Mild symmetry < 50%

Marked asymmetry: > 50%

Continuity

Look at the suppressed (< 10 uV)or attenuated (< 50% of background amplitude but >10 uV )
Suppression attenuation periods:

< 1%: continuous EEG
1-9%: nearly continuous
10-49%: Discontinous
50-99%: Burst Suppression
>99%: suppressed EEG

EEG background

Sleep Staging

Present with normal N2 sleep transients.
Present with abnormal N2 sleep transients.
Present without N2 sleep transients.
Absent.

Reactivity

Present.
SIRPIDs: Stimulus Induced Rhythmic Periodic or Ictal Discharges.
Absent.
Unclear.

Symmetry

In frequency:

Symmetric.

Mild asymmetry: 0.5-1 Hz

Marked asymmetry: > 1 Hz

Cyclic Alternating Pattern of Encephalopathy:

Present.
Absent.
Unclear.

In amplitude:

Symmetric.

Mild symmetry < 50%

Marked asymmetry: > 50%

Epileptiform Discharges

Spike, polyspike or sharp wave

Morphology: sharp.
Width: different from the preceding and following
Asymmetry between the rising and falling part
Followed by a slow wave
Jumps out of background
Follows a field

Pattern

Meets 4 or more of

Same shape.
Same duration.
Repeats for 6 cycles.
Inbetween the cycles the background may (periodic)
OR maynot (rhythmic) discharges.
Missing any of these criteria will switch the pattern to sporadic.

Types of Rhythmic and Periodic Patterns

Same shape & duration of the spikes.
Same interval between spikes for at least six cycles in a row.
Re-appearance of background inbetween each cycle.

Periodic Discharges

Rhythmic Delta Activities

Same shape & duration of the waveforms.
Same interval between spikes for at least six cycles in a row.
No appearance of background inbetween each cycle.

Spike and Wave

There has to be a wave after each (spike, sharp wave or poly-spike)
Should happen for at least 6 cycles in a row.
No appearance of background inbetween each cycle.

Localization of Rhythmic and Periodic Patterns

BOTH:

Synchronus (similar on the same hemispher).
Symmetric (similar on both hemispheres).

Generalized

Lateralized

Unilateral:

Appears only on one hemisphere.

Bilateral asymmetric:

Appears on both hemispheres but the amplitude is higher than 50% on a side.

Bilateral asynchronus:

Appears on both hemispheres but doesn’t start at the same time.

Independant

Unilateral Independant:

Asynchronus discharges.

Bilateral Independent:

Two asynchronus patterns one on each hemisphere.

Multifocal

BOTH:

Three asynchronus patterns.
At least, one on each hemisphere.

Modifiers for Interictal Patterns

Frequency

Typical frequecy.
Minimum and maximum range.
Use increments of 0.5 Hz from 0 to 4 Hz

Voltage

Very low: 20 mV
Low: 20 to 49 mV
Medium: 50 to 149 mV
High: > 150 mV

Prevalance

Continuous: > 90% of record
Abundant: 50% to 89%
Frequent: 10% to 49%
Occasional: 1% to 9%
Rare: <1%

Duration

Very long: > 1 hour.
Long: 10 to 59 minutes.
Intermediate: 1 to 9.9 minutes.
Brief: 10 to 59 seconds.
Very brief: 10 seconds.

Evolution of Interictal Discharges

Two changes in a row.
In the same direction (increasing or decreasing).
Each frequency Lasting between three seconds and five minutes.

Frequency

Morphology

Two changes in a row.
Each new shape lasts at least three seconds.

Location

Spread into adjasent leads.
Each new lead should have the discharges between three seconds and five minutes.

Notice:

No evolution in the amplitude.
Fluctuation: any three or more changes within a minute that doesn’t qualify for evolution.

Electrographic Seizure

Run of 10 seconds of epileptiform discharges.
It has to be > 2.5 Hz.

Epileptiform Discharges

Evolution

Any tupe of evolution.
Last >10 seconds.

Electrographic status epilepticus if:

One seizure longer than 10 mins.
Multiple seizures sums upto 20% of each hour.

Notice: