8-5-2022 ‫كلية طب نينوى‬

‫علي عادل الحيالي‬.‫د‬

‫أطفال‬ CNS)4( ‫محاضرة‬

STATUS EPILEPTICUS

Status epilepticus is a medical emergency defined as continuous seizure activity or

recurrent seizure activity without regaining of consciousness lasting for more than 5 min.
In the past, the cutoff time was 30 min, but this has been reduced to emphasize the risks
involved with the longer durations.

 Status epilepticus may be classified as generalized (tonic-clonic, absence) or partial .

 Generalized tonic-clonic seizures predominate in cases of status epilepticus.
 Status epilepticus is most common in children younger than 5 yr of age, with an
incidence in this age group of >100 per 100,000 children.
 Approximately 30% of patients presenting with status epilepticus are having their
first seizure, and approximately 40% of these later develop epilepsy.
 Febrile status epilepticus is the most common type of status epilepticus in children.

Pathophysiology

During status epilepticus there is increased cerebral metabolic rate and a compensatory
increase in cerebral blood flow that, after approximately 30 min, is not able to keep up with
the increases in cerebral metabolic rate. This leads to a transition from adequate to
inadequate cerebral oxygen tensions and, together with other factors, contributes to both
neuronal necrosis and apoptosis.

Etiology:

 Prolonged febrile seizures

 In children with epilepsy it could be : initial presentation of epilepsy of any type,
sudden withdrawal or overdose of antiepileptic drugs, intercurrent infections, sleep
deprivation ,non compliant patient with poorly controlled epilepsy.
 Drug intoxication (e.g., tricyclic antidepressants)
 Metabolic : hypoglycemia, electrolyte imbalance (hypocalcemia, hyponatremia,
hypomagnesemia) and inborn errors of metabolism.
 Acute head trauma, encephalitis, meningitis, ischemic stroke, intracranial
hemorrhage,brain tumors, brain malformations,hypoxic-ischemic injury
  Systemic conditions (such as hypertensive encephalopathy, renal or hepatic
encephalopathy).
 Idiopathic status epilepticus, in which a seizure develops in the absence of an
underlying CNS lesion or insult.

Investigation :

1) Laboratory studies: serum glucose, sodium, calcium , blood and spinal fluid cultures,
toxic screen and tests for inborn error of metabolism. Antiepileptic drug levels if patient is
already on an antiepileptic.

2) EEG: is helpful in identifying the types of status epilepticus.

3) Neuroimaging: needs to be considered after the child has been stabilized.

Management :

1) General steps

ABC :

 The first priority of treatment is to ensure an adequate airway and to assess the
cardiovascular status
 The child's oropharynx should be cleared and suctioned,
 Oxygen is administered.
 If there is any doubt concerning the adequacy of the airway, the child should be
intubated.
 Proper positioning : put patient onside and gently hyperextend the neck and jaw to
enhance breathing

IV ACESS+ BL.SUGAR:

 An IV infusion should be started.

 Immediate laboratory tests
- Glucose
- Basic metabolic panel (sodium, calcium, magnesium)
 If hypoglycemia is confirmed by Dextrostix, a rapid infusion of 5 mL/kg of 10%
dextrose is provided
2) Stop the convulsion by Anticonvulsants:
Rapid acting (Benzodiazepine) plus Long acting drugs(phenytoin, Fosphenytoin,
phenobarbital)
 i. Benzodiazepine (diazepam, lorazepam, or midazolam) effective for immediate control
of prolonged tonic-clonic seizures in most children.

Diazepam:

- IV directly 0.1–0.3 mg/kg , may repeat in 5-10 min for a maximum of three doses.
- Rectally 0.3-0.5 mg/kg
- rectal gel 0.2–0.5 mg/kg.
- it carries a risk of apnea and hypotension,so it is given over 3-5 min when given iv

Midazolam:

- Intravenous 2.0 mg/kg (may repeat in 5-10 min)

- Intramuscular 0.2 mg/kg
- Intranasal 0.2 mg/kg
- Buccal 0.5 mg/kg
- SE: hypotension & respiratory depression

Lorazepam :

- IV 0.1 mg/kg slowly (may repeat in 5-10 min)

- Rectally 0.1 mg/kg
- Intranasal 0.1 mg/kg
- is an equally effective short-term anticonvulsant, with a greater duration of action
and decreased likelihood of producing hypotension and respiratory arrest.
 If the convulsive activity ceases after diazepam or lorazepam therapy or if the seizures
persist, Phenytoin or Phenobarbital is given immediately.(no response in 10 minutes),

ii. Phenytoin:
- loading dose 15- 20 mg/kg IV diluted with normal saline but not to glucose
solutions
- maintenance 5 mg/kg ÷ 2
- SE: the undiluted drug can cause pain, irritation, and phlebitis of the vein.
Arrhythmias and bradycardia rare, hypotension may also complicate IV
phenytoin .
Fosphenytoin
- water soluble
- less irritating after IV injection
- well absorbed after intramuscular injection
iii. Phenobarbital: In some centers, phenobarbital is initiated before phenytoin.
 Loading in children 15-20 mg/kg and in neonates 20-30 mg/kg
 Maintenance 3-5 mg/kg ÷ 2.

Refractory status epilepticus: is status epilepticus that has failed to respond to therapy, usually
with at least 2 medications (such as a benzodiazepine and another medication) .

iv. If the status convulsion is not controlled by the preceding strategy (no response in
10 minutes)
 By this stage, the patient is usually sedated and may show signs of respiratory
depression, necessitating elective intubation and assisted ventilation.
 The choices for further drug management include :
 A diazepam infusion
 Constant IV infusion of either midazolam (0.20 mg/kg bolus, 60–300 μg/kg/hr
infusion).or
 Propofol (1–2 mg/kg bolus, 2–10 mg/kg/hr infusion).
 Barbiturate coma, in an intensive care unit, the patient is placed on a ventilator
and a continuous EEG monitor. The initial IV loading dose of thiopental is 2–4
mg/kg
 Paraldehyde, or is relatively safe for administration to children in a glass bottle ,
because the drug is incompatible with plastic ,diluted with D5W.
v. General anesthesia if conventional drug therapy is not effective or if barbiturate
coma is not an option. Several agents have been used successfully, including
halothane and isoflurane.
 PROGNOSIS.

 The mortality rate of status epilepticus is ≈5%. The greatest number of deaths
occur in the symptomatic group,
 long-term sequelae such as hemiplegia, extrapyramidal syndromes, mental
retardation, and epilepsy are more common in children younger than 1 yr
 The use of anticonvulsant therapy after status epilepticus is
controversialAnticonvulsant therapy is maintained arbitrarily for 3 mo in this
case and is discontinued if the child remains asymptomatic.

SEIZURES OF NEWBORN

Neonatal Seizures (NS) are the most important and common indicator of significant neurologic
dysfunction in the neonatal period. Its incidence is higher during this period than in any other period of
life.

Differences of the immature brain from the mature brain:

1) The immature brain is more excitable and more likely to develop seizures, but it appears to be
more resistant to the harmful effects of seizures than the mature brain
2) Neonatal seizures are dissimilar from those in a child or adult because generalized tonic-
clonic convulsions tend not to occur in the 1st mo of life. The branching of axons and
dendritic processes as well as myelination is incomplete in the neonatal brain. A seizure
discharge, therefore, cannot readily be propagated throughout the neonatal brain to produce a
generalized seizure.

Etiology of Neonatal seizures

1) Hypoxic-ischemic encephaolopathy:
 Usually occur 12-24hours after birth.
 There is history of birth asphyxia, also may be associated with metabolic disorder such
as hypoglycemia& hypocalcemia
2) IVH:
 is common cause of seizure in premature infants and occur between 1-3 days of age.
 Usually there is bulging fontanel, hemorrhagic spinal fluid, anemia, lethargy, coma
3) Hypoglycemia:
occur in at risk patients ,often occur when blood glucose levels decline to the lowest postnatal
value (at 1 to 2 hours of age or after 24 to 48 hours of poor nutritional intake)..
4) Hypocalcemia& hypomagnesemia
 5) Seizure in delivery room may be due to:
 Injection of local anesthetic agents in fetal scalp
 Severe anoxia.
 Congenital brain malformation.
6) Infection: Bacterial or viral infection of brain usually occur after 5days
7) Drug withdrawal: like methadone or heroin usually occur after 5days.
8) Inborn error of metabolism: Usually there is lethargy,acidosis,and family history of infant
death
9) Neonatal Seizure Syndromes
benign idiopathic neonatal seizures (fifth day fits)
Autosomal dominant benign familial neonatal seizures
10) Other causes
 Subarachnoid hemorrhage
 Benign familial seizure
 Vit B6 deficency or dependency

Clinical features and types of neonatal seizures

1. Subtle; It is more common in premature infant and include: transient eye deviations,
nystagmus, blinking, mouthing, abnormal extremity movements (rowing, swimming, bicycling,
pedaling, and stepping), fluctuations in HR, HT episodes, and apnea.
2. Clonic; It consist of jerky movement of extremities. It could be focal or multifocal. Multifocal
clonic seizures incorporate several body parts and are migratory in nature.
3. Tonic; It is either focal as persistent posturing of a limb, trunk or neck in an asymmetric way
often with persistent horizontal eye deviation, or generalized; which is more common &
associated with bilateral tonic limb extension or tonic flexion of upper extremities.
4. Myoclonic; It can be distinguished from clonic seizures by the rapidity of the jerks and by their
lack of rhythmicity, it can be divided into focal, multifocal, and generalized.

Differential diagnosis
 Jitteriness & tremor:
jitteriness is characterized by fine, rapid movement which can be elicited by stimuli,and
interrupted by holding the extremity ,not associated with abnormal eye movements and
absence of autonomic changes (tachycardia, salivation)

 Apnea : is associated with bradycardia

Investigations
1- Immediate determination of capillary blood glucose with strip.
2- blood glucose,calcium,sodium,&bilirubin determination.
3- when infection suspected cerebrospinal fluid and blood culture.

Other investigations done in selected cases:

 MRI,C.T scan,or ultrasound of brain for intracranial hemorrhage or brain malformations.

 EEG: often demonstrates seizure activity when clinical diagnosis is uncertain especially in
subtle seizure.
  Test for inborn error of metabolism

Treatment
1- Specific: such as treatment of meningitis, hypoglycemia, hypocalcemia, hypomagnesemia,
hyponatremia, or vit b6 deficency or dependency.
2- Treatment of seizure:

Phenobarbital is considered the first drug of choice The usual loading dose is 20 mg/kg. If this
dosage is not effective, the dose can be increased until amaximum dose of 40 mg/kg is reached.
Maintenance dose usually started 24 hr after the loading dose as 3-6 mg/kg/day ÷ 2

Phenytoin can only be started when the total loading dose of phenobarbital that reached 40 mg/kg
was not effective. The loading dose is 15-20 mg/kg, usually given by infusion (not in dextrose
solutions) with monitoring of HR to prevent cardiac dysrhythmia. Maintenance dose 4-8 mg/kg/day.

Diazepam is highly lipophilic, it distributes very rapidly into the brain and then is cleared very quickly
out (which carry a risk of recurrence of seizures). The usual dose is 0.1-0.3 mg/kg IV over 3-5 min,
given every 15-30 min to a maximum total dose of 2 mg. Diazepam is currently not recommended as
a first-line agent for neonatal seizures because it carries a higher risk of apnea and hypotension,
especially if the pt is also on phenobarbital, thus patients should be observed for 3-8 hr after
administration.

Second and third choice for neonatal Seizures :Levetiracetam (Keppra) and Topiramate(Topamax)

NEUROCUTANEOUS DISORDERS
The skin , teeth , hair , nail and the brain are derived embryologically from ectoderm , so abnormalities
in these structure may be associated with abnormal brain development. these include:

 Neurofibromatosis
 Tuberous sclerosis
 Sturge-weber disease
 Ataxia telangiectasia

Neurofibromatosis (NF)
 A.D disorder.
 Cardinal feature of disorder are café-au-lait spots , axiliary freckling , cutaneous
neurofibromas , iris hamartomas
 There are two types of NF, NF-1 and NF-2

Criteria for diagnosis of NF-1:

Definitive diagnosis required at least 2 criteria of the following 7 :

1. Six or more café-au-lait spots (size should be: in pretpubertal individuals >0.5cm , in
postpubertal individuals >1.5cm)it is the hallmark of neurofibromatosis and are present in
almost 100% of patients.
 2. Two or more neurofibromas or one plexiform neurofibroma

3. Axillary or inguinal freckling

4. Optic glioma.

5. Two or more iris Lisch nodules (iris hamartoma).

6. Distinctive bone lesion such as sphenoid dysplasia which may cause pulsating
exophthalmos.

7. 1st degree relative with NF-1.

Complication:

 Learning disability and cognitive abnormalities

 Scoliosis ,
 Macrocephaly and hydrocephalus
 Neurologic complications as epilepsy
 Malignant neoplasms neurofibrosarcoma , malignant schwannoma ,astrocytomas and
pheochromocytoma
 Hypertension, which may result from renal vascular stenosis or associated a
pheochromocytoma
Tuberous sclerosis
 A.D disorder, two thirds of cases are sporadic and thought to represent new mutations.
 Classic triad :
o Facial angiofibroma (adenoma sebaceum) develop between 4 and 6 yr of age; they
appear as tiny red nodules over the nose and cheeks and are sometimes confused with
acne
o Mental retardation
o Severe epilepsy
 It is acommon cause of infantile spasm.
 More than 90% of cases show the typical hypomelanotic macules that have been likened to an
ash leaf on the trunk and extremities which are apparent in infancy.
 A shagreen patch is also characteristic of TS and consists of a roughened, raised lesion with
an orange-peel consistency located primarily in the lumbosacral region that develop in late
childhood or early adolescence.
 subungual fibromas
 Tubers in the cerebral cortex are areas of dysplasia that responsible for the symptoms of
mental retardation and epilepsy.
Other clinical features:

 Retinal hamartoma
 Renal hamartoma
 Cardiac rhabdomyoma
 Mental retardation
 Myoclonic atonic, partial , grand mal seizures

Diagnosis :

 Clinical suspicion
 Typical skin lesions
 CT / MRI

Treatment:

Control of seizure
Educational services for MR
Cosmetic
Monitoring & follow up of systemic involvement
Sturge-Weber Syndrome
Angioma of the leptomeninges(arachnoid and pia mater) overlying the cerebral cortex in association
with ipsilateral facial port-wine nevus (in the 5th cranial N. distribution ).

 This syndrome is a sporadic disorder

 Seizure is the common clinical feature due to ischemia of underlying brain.
 Locations of angioma include posterior parietal ,temporal &anterior occipital
 Progressive ischemia produce hemiplegia contralateral to the cutaneous and brain lesions &
intractable seizures
 mental retardation or severe learning disabilities are present in at least 50% in later
childhood, probably the result of prolonged generalized seizures and increasing cerebral
atrophy secondary to local hypoxia and use of numerous anticonvulsants
  Glaucoma of the ipsilateral eye are common complications
 Not all children with facial nevi have Sturge-Weber syndrome (A child born with a port-wine
stain on the face has approximately a 6% chance of having the Sturge–Weber syndrome, and
this risk increases to 26% when the port-wine stain is located in the distribution of the
ophthalmic branch of the trigeminal nerve)

Diagnosis

 x-ray (railroad track) calcification in 60%

 CT scan highlights the extent of the calcification that is usually associated with unilateral
cortical atrophy and ipsilateral dilatation of the lateral ventricle

Treatment : anticonvulsant therapy + laser therapy for cosmetic