Salient Features

An 11 month-old male infant was rushed to the hospital because of first-onset and single episode of

generalized seizure.

The infant was noted to be coughing with nasal catarrh for the last 5 days. Hours before the seizure

episode, his temperature was taken to be 38.9C. Perinatal and postnatal histories were

unremarkable.

The father admitted to be having the same episodes when he was still around 5 years old during the

height of his fever. Neurological examination was normal.

Salient Features

Clinical Impression

Febrile Seizure

DIFFERENTIAL DIAGNOSIS

DIFFERENTIAL DIAGNOSIS

1. Meningitis2. Encephalitis3. Epilepsy

MENINGITIS

• Is an inflammation of the membranes (meninges) and cerebrospinal fluid surrounding the brain and spinal cord, usually due to the spread of an infection

• The swelling associated with meningitis often triggers the "hallmark" symptoms of this condition, including headache, fever and a stiff neck

• Most cases of meningitis are caused by a viral infection, but bacterial and fungal infections also can lead to meningitis– Bacterial infections are the most damaging,

identifying the source of the infection is an important part of developing a treatment plan

• Depending on the cause of the infection, meningitis can resolve on its own in a couple of weeks — or it can be a life-threatening emergency

• ACUTE BACTERIAL MENINGITIS– Usually occurs when bacteria enter the

bloodstream and migrate to the brain and spinal cord

– Can directly invade the meninges, as a result of an ear or sinus infection or a skull fracture

– Streptococcus pneumoniae (pneumococcus)• Most common cause of bacterial meningitis in infants

and young children in the United States.

– Neisseria meningitidis (meningococcus)• Another leading cause of bacterial meningitis • It commonly occurs when bacteria from an upper

respiratory infection enter your bloodstream.• Highly contagious and may cause local epidemics in

college dormitories and boarding schools and on military bases

– Haemophilus influenzae (haemophilus)• Before the 1990s, Haemophilus influenzae type b (Hib) bacterium

was the leading cause of bacterial meningitis. • Hib vaccines —routine childhood immunization

– Greatly reduced the number of cases of this type of meningitis• It tends to follow an upper respiratory infection, ear infection

(otitis media) or sinusitis

– Listeria monocytogenes (listeria)• These bacteria can be found almost anywhere — in soil, in dust

and in foods that have become contaminated– Soft cheeses, hot dogs and luncheon meats

• Most healthy people exposed to listeria don't become ill– Pregnant women, newborns and older adults tend to be more

susceptible. • Listeria can cross the placental barrier, and infections in late

pregnancy may cause a baby to be stillborn or die shortly after birth

• Viral meningitis– Usually mild and often clears on its own within two weeks– A group of common viruses known as enteroviruses are responsible

for about 90 percent of viral meningitis in the United States– Most common signs and symptoms: Rash, sore throat, joint aches

and headache– “Worst headache I've ever had“

• Chronic meningitis– Ongoing (chronic) forms of meningitis occur when slow-growing

organisms invade the membranes and fluid surrounding the brain– Although acute meningitis strikes suddenly, chronic meningitis

develops over four weeks or more– Signs and symptoms: Headaches, fever, vomiting and mental

cloudiness– This type of meningitis is rare

• Fungal meningitis– Relatively uncommon – Cryptococcal meningitis

• Fungal form of the disease that affects people with immune deficiencies, such as AIDS

– Life-threatening if not treated with an antifungal medication

• Other meningitis causes– Meningitis can also result from noninfectious causes, such

as drug allergies, some types of cancer and inflammatory diseases such as lupus

Harrison’s Principles of Internal Medicine, 17th Edition

ENCEPHALITIS• “Inflammation of the brain," it usually refers to

brain inflammation resulting from a viral infection– Primary encephalitis

• Involves direct viral infection of the brain and spinal cord– Secondary encephalitis

• A viral infection first occurs elsewhere in the body and then travels to the brain

• In contrast to viral meningitis, where the infectious process and associated inflammatory response are limited largely to the meninges, in encephalitis the brain parenchyma is also involved

• It can be caused by:– Bacterial infection

• Spreads directly to the brain (primary encephalitis)• Bacterial meningitis

– A complication of a current infectious disease • Syphilis (secondary encephalitis)

– Parasitic or protozoal infestations• Can also cause encephalitis in people with compromised immune

systems• Such as toxoplasmosis, malaria, or primary amoebic

meningoencephalitis– Lyme disease and/or Bartonella henselae may also cause

encephalitis

EPILEPSY

• Classified as a disorder of at least two unprovoked recurrent seizures

• More common in young and old, plateau at 2nd – 4th decades of life

• In children (0-14 years old)congenital> trauma=infection>CVA=tumor

• Genetic Predispostion– The direct result of a known or presumed genetic

defect in which seizures are the core symptom of the disorder• Examples include childhood absence epilepsy,

autosomal dominant nocturnal frontal lobe epilepsy, and Dravet syndrome

• Epileptic Seizures– No sexual predisposition, may occur at any age– Loss of consciousness is common– Onset is usually abrupt and may have a short aura– Vocalization is present during automatism

Dravet’s Syndrome• Severe myoclonic epilepsy of infancy (SMEI) • Generalized epilepsy syndrome • Onset is in the first year of life • Peaks at about 5 months of age with febrile

hemiclonic or generalized status epilepticus • Boys are twice as often affected as girls• Prognosis is poor

• Most cases are sporadic• Family history of epilepsy and febrile

convulsions is present in around 25 percent of the cases

• Known causative genes are the sodium channel α subunit genes SCN1A and SCN2A, an associated β subunit SCN1B, and a GABAA receptor γ subunit gene, GABRG2

Pathophysiology

FEBRILE SEIZURES

Febrile Seizure• Most common type of seizure that occurs during childhood that is

associated with a febrile illness not caused by an infection of the central nervous system (CNS), without previous neonatal seizures or a previous unprovoked seizure, and not meeting the criteria for other acute symptomatic seizures (International League Against Epilepsy)

• Rare before 9months and after 5 years of age• The peak age of onset is 14-18 months• A strong family history of febrile convulsions in siblings and parents

suggests a genetic predisposition.– In a child with febrile seizure, the risk of febrile seizure is 10% for the

sibling and almost 50% for the sibling if a parent has febrile seizures as well

Reference: Nelson’s Pediatrics 18th ed. and eMedicine.medscape.com

Febrile Seizure• Febrile seizures are not associated with reduction in later

intellectual performance, and most children with febrile seizures have only a slightly greater risk of later epilepsy than the general population.

• Usually it takes the form of a single, generalized motor seizure occurring as the temperature rises or reaches its peak.

• Seldom does the seizure last longer than a few minutes; • By the time an EEG can be obtained, there is usually no

abnormality. • Recovery is complete


Risk Factors• Family history of febrile seizures• High temperature• Parental report of developmental delay• Neonatal discharge at an age greater than 28 days

(suggesting perinatal illness requiring hospitalization)• Daycare attendance• Presence of 2 of these risk factors increases the

probability of a first febrile seizure to about 30%.• Maternal alcohol intake and smoking during

pregnancy has a 2-fold increased risk.


Types of febrile seizure• Simple

– associated with a core temperature that increases rapidly to ≥39°C.

– It is initially generalized and tonic-clonic in nature– lasts a few seconds and rarely <15 min– followed by a brief postictal period of drowsiness– occurs only once in 24 hr.

• Complex– Duration is >15 min– Focal seizure activity or focal findings are present during the

postictal period.– Repeated convulsions occur within 24 hr


Recurrent Seizures• Approximately 30–50% of children have recurrent seizures with

later episodes of fever and a small minority has numerous recurrent febrile seizures.

• Risk factors for recurrent febrile seizures include the following:– Young age at time of first febrile seizure <12 mon.– Relatively low fever at time of first seizure– Family history of a febrile seizure in a first-degree relative– Brief duration between fever onset and initial seizure– Multiple initial febrile seizures during same episode

• Patients with all 4 risk factors have greater than 70% chance of recurrence. Patients with no risk factors have less than a 20% chance of recurrence.


Pathophysiology•Febrile seizures occur in young children at a time in their development when the seizure threshold is low.

•This is a time when young children are susceptible to frequent childhood infections such as upper respiratory infection, otitis media, viral syndrome, and they respond with comparably higher temperatures.

•Animal studies suggest a possible role of endogenous pyrogens, such as interleukin 1beta, that, by increasing neuronal excitability, may link fever and seizure activity.

•Preliminary studies in children appear to support the hypothesis


History• The type of seizure (generalized or focal) and its duration should be described

to help differentiate between simple and complex febrile seizures.• Focus on the history of fever, duration of fever, and potential exposures to

illness.• A history of the cause of fever (eg, viral illnesses, gastroenteritis) should be

elucidated.• Recent antibiotic use is particularly important because partially

treated meningitis must be considered.• A history of seizures, neurologic problems, developmental delay, or other

potential causes of seizure (eg, trauma, ingestion) should be sought.

Physical Examination• The underlying cause for the fever should be sought.• A careful physical examination often reveals otitis media, pharyngitis, or a viral

exanthem.• Serial evaluations of the patient's neurologic status are essential.• Check for meningeal signs as well as for signs of trauma or toxic ingestion.


MANAGEMENT

Diagnostics

• To determine the cause of the fever• To rule out meningitis or encephalitis

Lumbar Puncture with CSF examination

• cerebrospinal fluid (CSF) is essential in confirming the diagnosis of meningitis, encephalitis, and subarachnoid hemorrhage

Lumbar Puncture with CSF examination

• Contraindications:– elevated ICP owing to a suspected mass lesion of

the brain or spinal cord– symptoms and signs of pending cerebral

herniation in a child with probable meningitis– critical illness – skin infection at the site of the LP– thrombocytopenia

Lumbar Puncture with CSF examinationWBC Protein Sugar Others

Normal 0-5 lymphocyte 15-45

50-75>50% of

blood sugar

Clear

Acute bacterial

High neutrophil→

(after 5 days) lymphocytes

High Low Turbid

Viral N or slight increase Clear

TB High lymphocytes High Low <40 Xanthochromic

EEG• Not recommended after an initial simple

febrile seizure in children with a normal neurologic examination

• Typically does not identify specific abnormalities or help predict recurrent seizures

• Consideration of EEG if febrile seizures are complex or recurrent

http://www.merck.com/mmpe/sec19/ch283/ch283c.html

TREATMENT

Treatment for Nasal catarrh

• Pseudoephedrine/Dextromethorphan can be given for the cough and decongesting the airways of the infant.

• It works by constricting blood vessels and reducing swelling in the nasal passages, which helps you to breathe more easily. The cough suppressant works in the brain to help decrease the cough reflex.

• However, you should not use decongestants for more than 5-7 days at a time. This is because they can only provide short-term relief for catarrh, and using them for any longer can make your symptoms worse.

Medical Treatment

• Treatment of infants with seizures is different than treatment for adults. Unless a specific cause is found, most infant with first-time seizures will not be placed on medications.

Medical Treatment• Phenobarbital

- enhances the inhibitory actions of gamma-aminobutyric acid (GABA) on neurons. - decreases the occurrence of subsequent febrile seizures.- Oral Dosage (as recommended by the American Academy of Pediatrics): 1 to 3 mg/kg.

Medical TreatmentBenzodiazepine• Centrally acting muscle

relaxant. • Gel, rectal 2.5 mg (pediatric)• Anticonvulsant properties

may be in part or entirely due to binding to voltage-dependent sodium channels.

• It can reduce the risk of subsequent febrile seizures.

• Because it is given intermittently, this therapy probably has the fewest adverse effects. If preventing subsequent febrile seizures is essential, this would be the treatment of choice.

Medical Treatment• Paracetamol(Acetaminop

hen)- inhibits prostaglandins in CNS, but lacks anti-inflammatory effects in periphery; reduces fever through direct action on hypothalamic heat-regulating center.

-15 mg per kilogram of weight; taken once every 4 hours, up to 4 times per day if needed

PREVENTION

Prevention• Most seizures cannot be

prevented.

• There are some exceptions, but these are very difficult to control, such as head trauma and infections during pregnancy.

• Children who are known to have febrile seizures should have their fevers well controlled when sick.

Prevention

• The best way to prevent fevers is to reduce the infant's exposure to infectious diseases.

• Hand-washing is the single most important prevention measure for people of all ages.

PreventionIf another seizure ensues: • The initial efforts should be

directed first at protecting the infant from additionally injuring himself.

• Lie down the infant.• Remove glasses or other

harmful objects in the area.• Do not try to put anything in

mouth. In doing so, it may injure the infant.

• Immediately check if the infant is breathing. Call a doctor or proceed to the nearest hosp.

Documents

Salient Features