UNIT: Internal Medicine

REG NO.: BMS/2014/72732

DATE: 30/7/2021

ASSIGNMENT: Status Epilepticus

STATUS EPILEPTICUS

Introduction

In 1993 the American Epilepsy Society Working Group had put forward an operational
definition of status epilepticus as a continuous seizure lasting more than 30minutes or two or
more seizures without full recovery of consciousness in between them, the rationale for
stipulating this duration was the observation from experimental models that any seizure that
persist for more than 30 minutes accompanied by serious metabolic decompensation and
permanent neuronal damage.

Currently it is recommended that seizures lasting more than 5 minutes should be managed as
status epilepticus.

Recurrent Status Epilepticus is defined as continuous or repetitive seizures lasting longer

than 60 minutes despite treatment with benzodiazepines and another standard anticonvulsant
i.e phenytoin or fosphenytoin.Risk factors for RSE are: Underlying structural cerebral
damage or metabolic disorders or cerebral hypoxia, delay in receiving treatment, metabolic
ecephalopathy, hypoxia and encephalitis.

Prolonged status epileticus can lead to:

 Cardiac dysrhyrthmias,
 metabolic derangements
 Autonomic dysfunction
 Neurogenic pulmonary edema
 Hyperthermia
 Rhabdomyolysis
 Pulmonary aspiration
Classification

Is based on electro-clinical; features .Broadly classified as :

1. Non-convulsive status epilepticus

2. Convulsive status epilepticus

Convulsive status epilepticus

 Tonic-clonic status epilepticus

 Tonic stats epilepticus
 Clonic status epilepticus
 Myoclonic status epilepticus

Non-convulsive Status epilepticus

Near continuous generalized electrical seizures activity lasting for at least 30 minutes but
without physical convulsions.

It is characterized by abnormal mental status, un-responsiveness, ocular motor abnormalities,

electrical electrographic seizures and possible response to anticonvulsants...It is further
divided into two classes:

 Absence status epilepticus[ASE]

 Complex partial status epilepticus
 Simple partial satus epilepticus

Most cases of ASE are actual cases of CSPE that have generalizaed.ASE is easier to treat and
is not associated with neuronal damage.
Epidemiology

 Status epilepticus is more frequent among ,male, blacks and aged.

 Among the elderly persons older than 60 yrs and among the younger age group
children below 25 yrs and infants younger than 12 months have the highest incidence.
 Incidence of 6.2-18.3% per 1000000 has been reported in the US
 It is more frequent among the elderly population
 The mortality rate increases with age; 3 % among children, 265 among adults and
38% among elderly population based on Richmond study.

Etiology

 Pre-existing history of epilepsy; dramatic drop in serum levels of anti-epileptic drugs

due to non-compliance.
 Central nervous system infections may predominate in children i.e cerebral malaria
 Genetic factors
 For PITC reactive patients cerebral toxoplasmosis ,lymphoma and anti-convulsants
withdrawal are common causes
 Electrolyte imbalance
 Organ dysfunction
 Trauma
 Hypertensive encephalopathy
 Hypoglycaemia
 Poisoning
 Alcohol withdrawal
 Stroke

Pathophysiology

It is divided into two phases; Initiation phase and maintenance phase

 The initiation phase is triggered by stimuli that evokes discrete features that tend to abate as
soon as stimuli is removed .In the maintenance phase discrete seizure coalesce together into a
continuum such that triggering stimuli is not required to sustain a train of seizure.

Intensity and duration n of stimulation has direct influence to the transition to maintenance
phase.

Signalling molecules such as GABA-An antagonists, glutamate agonists, tachykinins, and

galanin antagonists are found to be involved in the initiation phase.

Hypothesis-Within the limbic system the dentate gyrus acts as a gate keeper and prevents
excitatory stimulation from spreading through the hippocampus until a point of maximum
dentate activation is reached. Once this point is exceeded excitatory inputs can spread
through the hippocampus and may propagate to involve widespread cortical areas. Ineffective
recruitment of inhibitory neurons, together with excessive neuronal excitation plays a role in
initiation and propagation of electrical disturbance in status epilepticus.

GABA is a key inhibitory neuro- transmitter in the brain .GABA receptor mediated
inhibition may be responsible for termination of seizures. The activation of the NMDA
receptor by excitatory neurotransmitter results in increased levels of intracellular calcium
seen in patients with nerve cell injury seen in patients with status epilepticus.

Prolonged epileptiform bursting results in reduction of GABA mediated synaptic inhibition

.It has been noted that constitutive internalization of GABA–A receptors is rapid and
accelerated by neuronal activity associated with seizures while inhibition of neuronal activity
contributes to the reduction of inhibitory transmission observed during prolonged seizures
.GABA-A receptor internalization is regulated by neuronal activity and its acceleration
contributes to reduction of inhibitory transmission is observed in prolonged seizures

Stages of Status epilepticus

a)Stage of compensation < 30 min Generalized tonic-clonic seizures where cerebral energy
requirements are matched by supply of oxygen and glucose it is associated with an increase
autonomic activity resulting in hypertension, hyperglycemia, sweating, salivation and
hyper-pyrexia.In this phase cerebral blood flow is increased due to increased cerebral
metabolic demands.
b)Stage of decompensation .30 minutes after seizure activity patients enter second phase
which is characterized by failure of cerebral auto regulation ,decreased in cerebral blood
flow, increase in intracranial pressure and systemic hypotension, hypoxia, acidosis
,hyponatremia, disseminated intravascular coagulation ,hypo/hyperkalemia and
leukocytocis.Electoral seizure activity continues in spite of electromechanical
dissociation .whose clinical manifestation is restricted to minor twitching.

Distinct phases electrographic stages

1. Discrete electro-graphic seizures
2. Merging of electrographic seizures-waxing and waning of ictal discharges
3. Continuous ictal discharges
4. Continuous ictal discharges punctuated by flat periods
5. Periodic epileptiform discharges against a relatively flat background

Diagnosis

Clinical presentation of tonic-clonic movements with frothing and dys-autonomic features

with loss of consciousness is mainly used to diagnose convulsive status epilepticus.

Non-convulsive status epilepticus may be difficult in patients with subtle writhing and in-
phase limb movement and unresponsive behaviour.

The gold standard method of diagnosing status epileticus is video-EEG monitoring.

Investigation

 CSF studies
 Toxicology studies
 Metabolic studies for in-born errors of metabolism
 Neuro-imaging studies after stabilization
DIFERRENTIAL DIAGNOSIS

 Psychogenic status epilepticus

 Neuroleptic malignant syndrome
 Decerebrate spasms
 Paroxysmal dyskynesia
 Tetanus
 Shivering,clons,tetany,tremor
 Malignant hyperthermia
 Status dystonicus

TREATMENT

Rationale:Seziure control takes precedence over systemic evaluation

Principles of management

 Protection of vital function

 Early use of appropriate ant-convulsants
 Evaluation of cause for status epileptics
 Prevention of complications and recurrence of seizures
Initial

 Ensure adequate airway; provide respiratory support to prevent cerebral hypoxia

.Suction of the oropharynx should be done at the end of the seizure to prevent injury
to the patient.
 Check pulse, blood pressure and respiratory rate.
 Secure intra-venous access using two large-gauge intravenous catheters to facilitate
fluid resuscitation and pharmacotherapy. Alternatively central venous catheter is
recommended if peripheral venous access fails.
 Take blood samples for glucose, urea, electrolyte, calcium and magnesium, liver
function test and antiepileptic drug levels, full blood count and clotting screen
 IF seizures continue for >5min give diazepam 10mg iv or rectally or lorazepam 4mg
iv repeat once daily after 15 minutes.All benzodiazepines act by binding onto
benzodiazepine binding site on GABA receptor complex increasing GABA-ergic
transmission while barbiturates act directly on GABA receptors.
 Correct metabolic triggers;
1. Hypoglycemia-administartion of 50mls of 50% dextrose
and 100mg of thiamine intravenously if prompt
measurement of blood glucose is not possible
2. Monitor blood pressue,electro-cardiography and core body
temperature.
3. Maintain adequate hydration with normal saline in the
presence of myo-globinuria or significantly elevated
creatinine.>5000 to 10000 U/I

ONGOING
  When seizures continue after 30minutes
 IV infusion with cardiac monitoring with endotracheal intubation is required together
with nasogastric tube insertion to ensure the stomach is empty thus preventing
aspiration.
 Phonation 15mg/kg at 50mg/min; The main action of phonation is to block voltage
sensitive use dependent sodium channels
 Fosphenytoin 15mg/kg at 100mmg/min:
 Cardaic monitor and pulse oximetry moitor neurologic condition,blood
pressure,respiration check blood gases

If seizure still continues after 30-60 min

 Transfer to the intensive care unit

 Treatment for refractory status epilepticus intubation, ventilation and general
anaesthesia using propofol loading dose of 3 -5mg/kg as a loading and maintenance
infusion of 0-100mc/kg/min or thiopental
 With EEG monitor.

Once Status Controlled

 Commence longer term anti-convulsants medication:

 Sodium valproate 10mg/kg IV over 3-5 min, increase maintence dose to 800-
2000mg/day
 Phenytoin give loading dose –at 15mg/kg infuse at <50mg/min ,tube then 400-
1200mg/day
 Investigate cause.

Primary end-point for therapy suppression of encephalographic spikes when EEG monitoring
is done or ceasation of clinical manifestation of status epilepticus.

Complications

 Multiple organ dysfunction

 Medications to suppress immune response

Intervention associated complications

  Nosocomial and ventilator associated pneumonia
 Pneumonia
 Atelectasis
 Adult respiratory distress syndrome
 Neurogenic pulmonary edema
 Pulmonary Embolism
 Hypovolemia
 Myocardial dysfunction
 Stress ulcer
 Gastro-intestinal bleed
 Constipation
 Diarrhoea
 Paralytic ileus
 Renal dysfunction

PROGNOSIS

 Mortality varies from 3-50%,factors associated with high mortality include ;

 Refractory seizures,Acute symptomatic etiologies,impairment of consciousness,longer
duration of status epilpeticus >20 hours, old age >70 yrs,cardiovascular
decomensation during satus epilepticus,medical complications.
 Outcome of RSE is poor; mortality is almost 50% only minority of patients especially
those with ore-existing epilepsy return to their pre-morbid functional sate.

REFERENCES

Walker.B.R,College,N.K.,Ralston,S.H.,Penman.I.D.Davidson's Principles and Practice of

Medicine.Status epilepticus.pg.1159.22nd edition.
Papadakis.M.A,McPhee,S.J.Current Medical Treatment and Diagnosis.Tonic-clonic status
epilepticus pg.1008.I6th edition.

Sirven.J.I, Waterhouse .E,American Family Physician Journal.Management of Status

Epilepticus,2003.

Thomas.S.V.,Cherian ,A.,Annals of Indian Academy Neurology.Status Epilepticus,2009.