FEVER AND FEVER RELATED
EPILEPSIES (FIRES)
Azhar Daoud, MD, FRCP
Professor, Senior Consultant, Child Neurology 2013
Febrile infection-related epilepsy syndrome (FIRES),
Kramer et al 2011
2
Fever induced refractory epileptic encephalopathy in
school age (Nabbout 2011)
 Devastating encephalopathy in school age children,
mikealoff et al 2006
 New onset refractory status epileptics, wilder-smith et
al 2005
 Progressive myoclonic epilepsies
 Sever myoclonic epilepsy in infancy (Dravet’s
syndrome )
 Fever induced refractory epileptic encephalopathy,
Van Baalen et al 2010
 Idiopathic Catastrophic Epileptic encephalopathy,
Baxter et al, 2003

Electro-clinical Syndrome
3



Group of clinical entities that are reliably identified by a
cluster of electro-clinical and developmental
characteristics
Largely genetic in origin
Tend to have a strong relationship to developmental
aspects of brain
ILAE Commission 2009
Concept of Epileptic Syndromes
4

Factors taken into consideration include
 Seizure type(s)
 Age of Onset
 Precipitating factors
 Severity, Chronicity
 Diurnal/circadian cycling
 Etiology: genetics, structural pathology
 Associated neurological problems
 Interictal EEG
SEVERE MYOCLONIC EPILEPSY IN
INFANCY (DRAVET’S SYNDROME)
•
•
•
•
In a previously normal child, usually starts with
unilateral or bilateral clonic seizures accompanied
with fever.
Later myoclonic jerks supervene associated with
partial seizures with autonomic or atonic features
and automatisms may occur.
EEG shows generalized spike wave and polyskike
activity, photosensitivity and focal abnormalities.
Refractory to treatment and development arrest are
common
Characteristics of Dravet’s Syndrome
6








Age Limit
Affects normal healthy children
Different types of seizures
Difficult to control
Psychomotor retardation
Meticulous Management
Not only to treat seizure but to prevent delay
Poor outcome
OHTAHARA SYNDROME
•
•
•
Ohtahara Syndrome (OS) also known as
Early Infantile Epileptic Encephalopathy
with burst suppression (EIEE) is a progressive
epileptic encephalopathy.
It is an extremely debilitating progressive
neurological disorder, involving intractable
seizures and severe mental retardation.
No single cause has been identified,
although in many cases structural brain
damage is present.
Complex febrile seizures and Febrile
status epilipticus

Genetic and environmental( Helen Cross 2012)

Environmental is the fever, infection unknown

Rule out meningitis (AAP 2011)

EEG is not a justified investigation ( Nordli 2010)
Genetics
9





Polygenic inheritance as it is common in certain
families. Dominant
Several identified chromosomal loci(audenaert et al
,2006)
Sibling have 25% risk
SCN1A mutation with some member have milder
phenotypes (livingstone 2009)
Mutation with ion channel gene, thermoregulaion
and GABA kang 2006
Possible Etiology
10



Iron deficiency anemia and complex febrile
seizures, Azhar Daoud et al, 2002
Inflammatory process may influence neuronal
excitability dube et al ,2007
Alkalosis from fever induced hyperventilation
schuchmann et al, 2009
When it is not (just) FS
11




Meningitis simple versus complex (Batra et al, 2011
and Kimia et al,2010)
Is there a relationship to child immunization ,
Whooping cough
Berkovic et al 2006 11 out of the 14 with
encephalopathy are positive for SCN1A
The vaccine may trigger earlier onset of Dravet
Syndrome
FIRES Characteristics
12







Previously normal children with status e
Refractory to treatment lasting for days-wk
Preceding febrile illness
Poor Prognosis
Resultant refractory epilepsy
Profound neurocognitive deficit
Wide age range
FIRES Characteristics - ctnd
13





Apparently generalized but may have focal
semiology, Nabbout et al 2011
Repetitive in cluster or continuous
EEG, focal or multifocal
Initial MRI normal but later may show mesial
temporal signal
Inflammatory marker in serum and CSF are normal
Investigations
14

CSF May show minimal pleocytosis

CSF show negative oligoclonal bands

Receptor antibody studies ( voltage gated
potassium channel, N methyl D aspartate0 are also
negative, Nabbout 2011, although positive result
has been reported, illingworth et al 2011.
Theories
15




Unclear cause of encephalopathy
May have immune process
Genetic susceptibility is a possibility mainly PCDH
19 missense gene mutation specchio et al 2011.
SCN 1A is unlikely
Inflammatory mediators such as interleukin 1B, 1L-6
and tumor necrosis factors, Nabbout 2011
Management
16





Thiopental coma in ICU as they are resistant to AEDs
Lack response to immunosuppressive
Ketogenic diet may often help but this has not been
universal, nabbout 2011
Poor prognosis with mortality up to 30%
Seizure may disappear later on but with
devastating out come
Gastroenteritis related seizures
17






Recent entity
no fever, no dehydration, no electrolyte imbalance,
Uemura et al 2003
Age related 8-52 months
Average onset of 2.3 days from onset of GE
No child develop epilepsy out of 114
Some have clusters of seizures
18