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Neonatal and Pediatric Seizures

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					Neonatal and Pediatric
     Seizures


                            Hoorbod Delshadfar
                      3rd year student physician
               NY College of Osteopathic Med
              Nassau University Medical Center
                             Pediatrics Rotation
                                April-May 2005
                    Neonatal and Pediatric Seizures
•       Seizure Pathophysiology
    1.        Large group of neurons temporarily undergo excessive, synchronized depolarization
          •        excessive excitatory amino acid release (e.g, glutamate)
          •        deficient inhibitory neurotransmitter (e.g, GABA)
    2.        Disruption of ATP-dependent resting membrane potentials, which causes a flow of sodium
              into the neuron and potassium out of the neuron.
          •        Hypoxic-ischemic encephalopathy disrupts the ATP-dependent sodium-potassium
                   pump: It is an important cause of neonatal seizures.

•       Epilepsy = Seizure Disorder:
    –         A pattern of chronic seizures of any type over a long period.
    –         Thirty percent of children diagnosed with epilepsy continue to have repeated seizures into adulthood,
              while others improve over time (‘grow out of it’).

•       Status epilepticus:
    –         Either a seizure lasting longer than 30 minutes or repeated seizures without a return to normal in
              between them.
    –         It is most common in children younger than 2 years, and most of these children have generalized tonic-
              clonic seizures.
    –         Status epilepticus is very serious. With any suspicion of a long seizure, 911 should be called
                      Epidemiology/statistics
•   As high as 5% of children will have a seizure sometime during childhood.
•   Incidence of seizures is higher in the neonatal period (i.e, the first 4 weeks after birth
    (especially the first 10 days of life)) than in any other age group.
•   Febrile seizures (with infectious etiology) are frequent in infancy and young childhood.
•   Idiopathic epilepsy, on the other hand, is the most common type in older children.
•   About 1-2% of the general population suffers from epilepsy.
•   The presence of neonatal seizures is the best predictor of long-term physical and
    cognitive deficits
•   No race or sex predisposition seen.
•   Many children who experience a first seizure may never experience a second seizure.
    However, a seizure may be the initial presentation of a more serious medical condition.
                             Types of Seizures
    International Classification of Epileptic Seizures
A: Partial Seizures
    – 1:Simple seizures (intact consciousness)
        • Motor
        • Sensory
        • Autonomic
        • Psychic
    – 2: Complex Partial (impaired consciousness)
    – 3: Partial Seizures with secondary generalization
B: Generalized Seizures
    –   Absence (AKA petit mal) (typical and atypical)
    –   Tonic
    –   Clonic
    –   Tonic-Clonic (AKA grand mal)
    –   Myoclonic
    –   Atonic
    –   Infantile spasms
                                        Partial Seizures
•   An episode of abnormal activity in a localized (specific) part of the brain which causes
    changes in attention, movement, and/or behavior.
     – simple (not affecting awareness and memory)
     – complex (affecting awareness and memory of events before, during, and immediately after the
       seizure, and affecting behavior).
•   They last only a short time, usually less than 2 minutes and are remarkably different from
    person to person, depending on the part of the brain where they begin
•   They include:
     – Motor (Jacksonian) ( jerking of a finger or stiffening of the body, weakness, which can even affect
       speech, and coordinated actions such as laughter or automatic hand movements )
     – Sensory (any of the senses: smell or taste things that aren't there; hear clicking, ringing, or a person's voice
         when there is no actual sound; or feel a sensation of "pins and needles" or numbness. They may feel as if they
         are floating or spinning in space. They may have visual hallucinations, seeing things that aren't there (a spot of
         light, a scene with people). They also may experience illusions, distortions of true sensations: may believe that
         a parked car is moving farther away, or that a person's voice is muffled when it's actually clear)
     – Autonomic (strange or unpleasant sensations in the stomach, chest, or head; changes in the heart rate or
         breathing, sweating, or goose bumps)
     – Psychic (may suddenly feel emotions like fear, depression, or happiness with no outside reason. Some may
         feel as though they are outside their body or may have feelings of déja vu or jamais vu ("This is new to me"
         even though the setting is really familiar. They may have problems with memory, garbled speech, an inability
         to find the right word, or trouble understanding spoken or written language.)
                                     Generalized Seizures
•   Clonic seizures: These movements often involve one extremity or one side of the body. The rhythm of the clonic
    movements is usually slow, 1-3 movements per second.
•   Tonic seizures: These may involve one extremity or the whole body. Generalized
    tonic seizures often manifest with tonic extension of both upper and lower limbs and
    also may involve the axial musculature in an opisthotonic fashion.
     – Generalized tonic seizures mimic decorticate posturing (the upper
         extremities flexed and adducted and the lower extremities in rigid extension).
•   Tonic-Clonic Seizures (grand mal): combines the characteristics of tonic and clonic seizures.
     –   The tonic phase comes first: all the muscles stiffen. Air being forced past the vocal cords causes a cry or groan. The person loses
         consciousness and falls to the floor. The tongue or cheek may be bitten, so bloody saliva may come from the mouth. The person
         may turn a bit blue in the face.
     –   Then comes the clonic phase: The arms and usually the legs begin to jerk rapidly and rhythmically, bending and relaxing at
         the elbows, hips, and knees. After a few minutes, the jerking slows and stops. Bladder or bowel control sometimes is lost as the
         body relaxes. Consciousness returns slowly, and the person may be drowsy, confused, agitated, or depressed.
•   Myoclonic (twitching) seizures: These may occur focally in one extremity or in several body parts (in which
    case they are described as multifocal myoclonic seizures).
•   Generalized myoclonic jerks: are possibly the clinical equivalent of infantile spasms.
•   Infantile spasms: commonly occur in children younger than 18 months. They are often associated with mental
    retardation and consist of sudden spasms of muscle groups, each lasting a few seconds but repeating more than a 100
    times in a row, causing the child to assume a flexed stature. They are frequent upon awakening and have a typical
    EEG pattern known as hypsarrythmia.
•   Absence seizures: also known as petit mal seizures, are short episodes during which the child stares or eye blinks,
    with no apparent awareness of their surroundings.
     –   usually do not last longer then a few seconds and start and stop abruptly as many as 100 times per day or more
     –   the child does not remember the event at all
     –   sometimes discovered after the child’s teacher reports daydreaming, if the child loses his or her place while reading or misses
         instructions for assignments.
                                          Febrile Seizure
•   Occurs when a child contracts an illness such as an ear infection, cold, or chickenpox accompanied by
    fever.
•   The most common type of seizure seen in children. (Two to five percent of children have a febrile
    seizure at some point during their childhood.)
•   Only 33% of children have a second episode, and only 50% of those have a third episode.
•   The long-term outlook is excellent (The vast majority of children with febrile seizures do not have
    seizures without fever after age 5, and febrile seizures only slightly increase the chance of developing a
    seizure disorder.)
•   Risk factors for later epilepsy include:
     –   Those who have spent more than 28 days in a neonatal intensive care unit
     –   Abnormal development before the febrile seizure (or any neurological abnormalities)
     –   Complex febrile seizures: These are defined as seizures that last longer than 15 minutes, more than one seizure
         in 24 hours, or seizures in which only one side of the body is affected.
     –   Seizures without fever in a parent or a sibling.


                                  Some other seizures to note:
•Benign rolandic epilepsy occurs in children aged 4-10 years who have nocturnal seizures that are characterized by
facial twitching and aphasia. Some children with benign rolandic epilepsy may have generalized tonic-clonic
seizures as well.
•Juvenile myoclonic epilepsy (JME) occurs in the teen years. In JME, individuals have generalized motor seizures,
myoclonic jerks, and staring spells that occur upon awakening.
•Lennox-Gastaut Syndrome: frequent occurrence of mixed, generalized seizures that are notoriously refractory to
medical treatment. (this entity and Infantile spasms are two devastating generalized seizure syndromes.)
        Causes of Neonatal (within 28 days of birth) Seizures
•   Metabolic: Hypoglycemia, electrolyte abnormalities, inborn errors of metabolism

•   Toxic: Maternal drug ingestion, neonatal drug withdrawal, inadvertent local anesthetic poisoning,
    bilirubin

•   Hemorrhagic: Intraventricular, subdural (seen in association with cerebral contusion, more common
    in term infants), subarachnoid (more common in term infants, occurs frequently and is not clinically
    significant), and germinal matrix-intraventricular hemorrhage (seen more frequently in premature than in
    term infants)

•   Infectious: Bacterial meningitis, viral encephalitis

•   Asphyxia: Hypoxic ischemic encephalopathy (frequently present within the first 72 hours of life)

•   Genetic/dysmorphic syndrome: Cerebral dysgenesis, chromosomal abnormalities, phakomatoses
    (tuberous sclerosis)

–   (Jitteriness must be differentiated from seizures in neonates. Jitteriness is not associated with ocular
    deviation. It is stimulus sensitive (e.g., easily stopped with passive movement of the limb). The
    movement resembles a tremor, and no autonomic changes are associated with it.)
                    Benign Neonatal Seizures
•   Benign familial neonatal seizures
     – typically occur in the first 48-72 hours of life
     – disappear by age 2-6 months
     – A family history of seizures is usual
     – Development is typically normal in these infants.
•   Benign idiopathic neonatal seizures
     – typically present at day 5 of life (i.e, fifth day fits) with the vast majority
       presenting between days 4 and 6 of life
     – often multifocal
     – CSF analysis is usually unremarkable.
•   Benign sleep myoclonus
     – benign condition in which rhythmic movements (which occur only during sleep)
       mimic seizures
     – may occur focally during non-rapid eye movement (NREM) sleep
          Differential dx of Neonatal Seizures
Benign Neonatal Convulsions
Cerebellar Hemorrhage
                                       •Complications:
Early Myoclonic Encephalopathy              •Hydrocephalus
Epileptiform Discharges
Herpes Simplex Encephalitis                 •Epilepsy
Neonatal Injuries in Child Abuse
Neonatal Meningitis                         •Cerebral palsy
Shuddering Attacks                          •Spasticity
Subarachnoid Hemorrhage
Subdural Hematoma                           •Feeding difficulties
Tuberous Sclerosis
Vein of Galen Malformation         Prognosis:
Viral Encephalitis
Viral Meningitis                   •If EEG background is normal, the prognosis is excellent.
                                   Normal development is likely.
Anoxia
Benign epilepsy syndromes          •Severe EEG background abnormalities indicate poor
Mitochondrial cytopathies          prognosis      cerebral palsy and epilepsy.
Myoclonic epilepsy
Myoclonus                          •The presence of spikes on EEG is associated with a 30%
Organic acidurias                  risk of developing future epilepsy.
Any of the several movement        •The prognosis following neonatal seizures that result
disorders: Tourette’s, spasmus
                                   from isolated subarachnoid hemorrhage is excellent, with
nutans, tics, essential tremor,
myoclonus, etc.                    90% of children not having residual neurological deficits.
                 Causes of Pediatric Seizures
•   Family history of seizures
•   Infections (e.g, meningitis)
•   Developmental problems such as cerebral palsy
•   Head trauma
•   Metabolic disorders
•   Drugs
•   Medications                          Some Differential dx:
•   Poisons                              •Febrile seizure
•   Disordered blood vessels
                                         •Fainting
•   Bleeding inside the brain
                                         •Breath-holding spells
•   Many yet undiscovered problems
                                         •Night terrors
                                         •Migraines
                                         •Psychiatric disturbances
                              History & Physical
•   A family history of neonatal convulsions may suggest that the infant has a genetic syndrome.
    Many of these syndromes are considered benign and frequently disappear within the neonatal
    period.
•   In the absence of other etiologies, a family history of neonatal seizures may suggest a good
    prognosis.
•   A detailed pregnancy (TORCH), delivery (type, complications, Apgar scores, etc.), and
    postnatal (drug withdrawal, Temp and BP instability, CNS Rubella, etc.) history is important.
•    Infants and children with seizures are frequently lethargic between seizures and often appear
    ill (post-ictal drowsiness).
•   A thorough interview and examination should be done
     –   child’s medical history, birth history, any recent illness, and any medications or chemicals that the child
         could have been exposed to.
     –   description of the event, specifically to include where it occurred, how long any abnormal movements
         lasted, and the period of sleepiness afterward.

•   Some important notes on physical exam:
     –   Temperature and vital signs need to be obtained, as these are important in the initial evaluation
     –   Examine for papilledema suggesting increased intracranial pressure
     –   Examine skin to rule out tuberous sclerosis( ash-leaf spots, shagreen patches, etc.), which frequently is
         associated with seizures
•   Findings of the neurologic examination between seizures may be normal
     – (However, neurologic examination abnormalities may be seen correlating with a focal or
        generalized neurologic syndrome.)
                                   Lab and Imaging
• Lab Studies:
   – Serum glucose and electrolytes, including calcium: transient neonatal hypocalcemia is a cause
     of neonatal seizures during the first 3 weeks of life.
   – CSF analysis should include tests checking for pleocytosis (lymphocytosis of the CSF), xanthochromia
     ( : This suggestive of blood breakdown), lactic acid and pyruvate (for evidence of
     mitochondrial cytopathies), polymerase chain reaction (PCR) for herpes virus, and glucose
     concentration (bacterial meningitis or glucose transporter defects)
   – TORCH (toxoplasmosis, rubella, CMV, herpes, syphilis) infection studies
   – Urine organic acids, U/A and Renal function tests: to rule out posthypoxic renal dysfunction
   – Serum amino acid assay
• Imaging Studies:
   – Cranial ultrasound (performed readily at the bedside; a valuable tool to quickly check for
     intracranial hemorrhage, particularly intraventricular hemorrhage)
   – Cranial CT scan (much more sensitive tool than ultrasound in detecting parenchymal
     abnormalities) or MRI (most sensitive test in determining the etiology of neonatal seizures,
     also looks for congenital malformations)
• Other Tests:
   – EEG plays a vital role in properly identifying and differentiating seizures from nonepileptic
     events
        • Perform an EEG to address specific concerns. For example, certain seizure types are associated with specific
          EEG patterns (e.g. 3hz for petit mal); therefore, an EEG may be helpful in classifying seizure type.
        • An EEG does not determine whether the patient had a seizure or if the patient has epilepsy. For example,
          10% of healthy individuals have an abnormal EEG, whereas 50% of patients with epilepsy have a normal
          first EEG.
   – Video EEG monitoring may be helpful when infrequent seizures persist
   – Echocardiography to rule out cardiac hypomotility as a result of more diffuse hypoxia
                                               Treatment
•   Acute neonatal seizures should be treated aggressively. A rigorous workup to determine an underlying etiologic
    cause should be initiated quickly
     – Electrolyte imbalances should be corrected
     – When an inborn error of metabolism is suspected, feeding should be discontinued
     – An EEG should be obtained
     – The key factor in deciding whether to medicate or not is the patient's estimated risk of seizure recurrence and
         EEGs are very helpful in this regard:
              Risk factor                                                    Relative increase in risk
              Epileptiform features on EEG…………………………..…….Threefold
              Symptomatic seizure (cause determined)…………………..…Twofold
              Patient asleep at time of initial seizure…………………..……Twofold
              Partial seizures………………………………………………...Slight increase
              Family history of seizures or epilepsy………….......................Slight increase
     – Antiepileptic drug therapy should be considered based on the above and clinical judgment
           •   Phenobarbital is the initial drug of choice
           •   If seizures persist, the use of phenytoin should be considered
           •   Benzodiazepines like Lorazepam (Ativan) can be considered
           •   EEG may be helpful in deciding when to stop AEDs: A general recommendation is to use AEDs for 3
               months and if the patient remains seizure free then medications may be tapered gradually.
            • Anti-pyretic medications should be considered to prevent further febrile seizures
•   If medications are started drug levels need to be followed and side effects need be looked for
      – Often, it takes weeks to months to adjust the medications, and sometimes more than one medicine is needed.
•   Finally, for drug-refractory seizures, implantation of the vagus nerve stimulation device or neurosurgical
    intervention (resection of parts of the brain) is an option
•   In every aspect of treatment, patient education is essential to ensure safety of the patient and efficacy of treatment
                                     Prognosis
The prognosis for children with seizures depends on the type of seizures. Most children do well, are
able to attend regular school, and have no limitations. The exceptions occur with children who
have other developmental disorders such as cerebral palsy and in children with neonatal seizures
and infantile spasms.

Many children "outgrow" seizures as their brains mature. If several years pass without any
seizures, medications are often stopped to see if the child has outgrown the seizures.

A seizure in general is not harmful unless an injury occurs or status epilepticus develops. Children
who develop status epilepticus have a 3-5% risk of dying from the prolonged seizure.

Children with febrile seizures "outgrow" them, but they often have repeated seizures when they
develop fevers while they are young. Some children with febrile seizures go on to have epilepsy, but
most believe the epilepsy is not caused (or started) by the febrile seizures.
                                References
• www.emedicine.com
    – First Seizure Pediatric Perspective, Kenneth J Mack, MD, PhD
    – Neonatal Seizures, Raj D Sheth, MD
    – Seizures in Children, Frank L Christopher, MD FAAEM, Robert R Westermeyer II, MD
      FAAEM
• www.postgradmed.com
   – Neurologic consultation for seizures When, why, and how to pursue, David M.
      Labiner, MD, Geoffrey L. Ahern, PhD, MD
• www.nih.gov
• http://www.epilepsy.com
• The Merck Manual online
• Blueprints Pediatrics, 3rd ed Bradley S. Marino, Katie S. Fine, Julia A.
  McMillan
• www.guideline.gov
Thank you

				
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