encephalopathy and status epileptics
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Encephelopathy
- a general alteration in brain function manifesting as an attentionaldisorder - between a hyperalert agitated state and coma, and typically refers to the commonly encountered clinical scenario of diffuse brain dysfunction felt to be due to a systemic, metabolic, or toxic derangement.
Global encephalopathy Delirium Sepsis Organ failure- hepatic, renal Medication related - sedatives, hypnotics, analgesics, H2 blockers, antihypertensives Drug overdose Electrolyte disturbance - hyponatremia, hypernatraemia,
hypoglycemia, hypocalcaemia Hypotension/hypoperfusion
Hypoxia Meningitis – bacterial, viral, fungal Encephalitis Subarachnoid hemorrhage ( SAH ) Wernicke's disease Seizure - postictal or nonconvulsive status Hypertensive encephalopathy Hypothyroidism- myxedema
Status Epilepticus Refers to continuous seizures or repititive, discrete seizures with impaired consciousness in the interictal period.Duration of seizure activity is 15 - 30 minutes. Consider status epilepticus as a situation in which the duration of seizures prompts the acute use of anticonvulsant therapy.
Can be – > Generalised Convulsive status epilepticus ( GCSE)
- persistent, generalised electrographic seizures, come and tonic-clonic movements
> Non-convulsive status epilepticus - persistent absence seizures or focal siezures, confusion or partially impaired consciousness and minimal motor abnormalities
Why should it draw your attention ?
Consequences of status epilepticus – > cardiorespiratory dysfunction,> hyperthermia,> metabolic derangements, and > irreversible neuronal injury
“ If appropriate therapy is delayed, SE can cause permanent neurologic sequelae or death …”
* CNS injury can occur even when the patient is paralyzed with neuromuscular blockade but continues to have electrographic seizures
Precipitating event ?
Anticonvulsant withdrawal or noncompliance ? Metabolic disturbances ?Drug toxicity ?CNS infection ? CNS tumors ?Refractory epilepsy ?Head trauma ?
Drugs which can cause seizures
• Antibiotics– Penicillins– Isoniazid– Metronidazole
• Anesthetics, narcotics– Halothane, enflurane– Cocaine, fentanyl– Ketamine
• Psychopharmaceuticals– Antihistamines– Antidepressants– Antipsychotics– Phencyclidine– Tricyclic antidepressants
Importance of EEG ?
After 30 - 45 minutes of uninterrupted seizures, the signs may become increasingly subtle. For example – Mild clonic movements of only the fingers or fine, rapid
movements of the eyes. Paroxysmal episodes of tachycardia, hypertension, and pupillary
dilation. In such cases, the EEG may be the only method of establishing the diagnosis. Perform EEG :- if the patient stops having overt seizures, yet remains comatose patient with GCSE has been paralyzed with neuromuscular
blockade in the process of protecting the airway.
Prolonged seizures
Duration of seizure
Life threatening
systemicchanges
DeathTemporary
systemicchanges
Respiratory
• Hypoxia and hypercarbia
- ß ventilation (chest rigidity from muscle spasm)- Hypermetabolism (Ý O2 consumption, Ý CO2
production)- Poor handling of secretions- Neurogenic pulmonary edema?
11
Hypoxia
• Hypoxia/anoxia markedly increase the risk of mortality in SE
• Seizures (without hypoxia) are much less dangerous than seizures and hypoxia
Hemodynamics
• Sympathetic overdrive – Massive catecholamine /
autonomic discharge– Hypertension– Tachycardia– High CVP
Exhaustion Hypotension Hypoperfusion
0 min 60 min
GlucoseG
luco
se
Seizure duration
30 min
SE
SE + hypoxia
• Hyperdynamic phase – Hyperglycemia
• Exhaustion phase– Hypoglycemia
develops– Hypoglycemia
appears earlier in presence of hypoxia
– Neuronal damage ensues
Hyperpyrexia
• Hyperpyrexia may develop during protracted SE, and aggravate possible mismatch of cerebral metabolic requirement and substrate delivery
• Treat hyperpyrexia aggressively– Antipyretics, external cooling– Consider intubation, relaxation, ventilation
Other alterations
• Blood leukocytosis (50% of children)• Spinal fluid leukocytosis (15% of children)• Ý K+
• Ý creatine kinase• Myoglobinuria
Management• Attend to any acute cardiorespiratory problems or
hyperthermia• Perform a brief medical and neurologic examination• Establish venous access• Send blood samples for laboratory studies to identify
metabolic abnormalities• Anticonvulsant therapy
Oxygen, oral airway. Avoid hypoxia!
Consider bag-valve mask ventilation. Consider intubation
IV/IO access. Treat hypotension, but NOT hypertension
A
B
C
Management
• Secure the Airway– It may be difficult to intubate the actively seizing
patient– Stop or slow seizures first, give O2, consider BVM
ventilation– If using paralytic agent to intubate, assume that SE
continues
Initial investigations
• Labs– Na, Ca, Mg, PO4 , glucose– CBC– Liver function tests, ammonia– Anticonvulsant level– Toxicology
Initial investigations
• Lumbar puncture– Always defer LP in unstable patient, but never delay
antibiotic/antiviral rx if indicated• CT scan
– Indicated for focal seizures or deficit, history of trauma or bleeding d/o
Correct Metabolic factors
• Hypoglycaemia – If RBS < 60mg %, use 25 % Dextrose iv fast– Monitor hourly Sugar levels
- Hyperglycemia has no negative effect in SE (as long as significant hyperosmolality is being avoided)
• Hyponatraemia :– Use 0.9 % NS, 3 % NS according to the severity of
hyponatraemia
• Hypocalcaemia :– Calcium gluconate or Calcium Chloride can be used
Anti-epileptic Drugs ( AED )
• The longer you wait with anticonvulsant, the more anticonvulsant you will need to stop SE
• Most common mistake is ineffective dose
Phenytoin or Diphenylhydantoin
• MOA-– Stablizing influence on neuronal membrane– prolongs the inactivated state of voltage sensitive
neuronal Na channel– high frequency discharges are inhibited
• Not a CNS depressant• T ½ = 12-24 hrs• Metabolized by hepatic ER by hydroxylation. Chance for
drug interactions.• Shift from first to zero order elimination within therapeutic
concentration range.
Adverse effects At therapeutic levels
• Gum hypertrophy – commonest– More in young– d/t gingival collagen overgrowth– Maintain oral hygiene
• Hirsutism, coarsening of facial features
• Megaloblastic anaemia – decrease folate absorbtion
• Osteomalacia- desensitizes target tissue to vit d
• Inhibit insulin release- hyperglycaemia
• Hypersensitivity rxns
At toxic doses
• Cerebellar & vestibular manifestations- ataxia, vertigo, diplopia, nystagmus
• Drowsiness, behavioral alterations, hallucinations, rigidity
• Nausea, vomiting• i.v. injection
– thrombosis of the vein – Cardiac arrythmias
Fetal Hydantoin Syndrome
When used during pregnancy
Hypoplastic phalanges
Hare lipCleft palatemicrocephaly
Interactions of phenytoin
• Levels are increased by – isoniazid, sulfonamides • Levels decreased by – enzyme inducing drugs
- phenobarbitone • Competitively inhibits warfarin metabolism
Fosphenytoin
• A Prodrug. Given i.v. or i.m. and rapidly converted to phenytoin in the body.
• Avoids local complications associated with phenytoin: vein irritation, tissue damage, pain and burning at site, muscle necrosis with i.m. injection, need for large fluid volumes.
• Otherwise similar toxicities to phenytoin.
Valproic Acid / Sodium Valproate
• Effective in multiple seizure types.• MOA-
– Phenytoin like frequency dependent prolongation of Na channel inactivation
– Ethosuximide like Weak attenuation of Ca mediated ‘T’ current
– Augmentation of GABA by inhbiting breakdown and increasing synthesis
Adverse effects
• Fulminant hepatitis– Occurs in children < 3 yrs of age– High risk patients with preexisting hepatic diseases or
who receive other anticonvulsant drug
• Polycystic ovarian disease & menstrual iregularities• During pregnancy- spina bifida & other neural tube defects• Anorexia, vomiting• Alopecia, curling of hair, increased bleeding tendency• Drowsiness, ataxia – dose related S/E
uses
• DOC for absence sz• Alternative/ adjunct drug for GTCS, SPS, CPS• Migraine- prophylactic efficacy• Mania and bipolar illness
Interactions
• Displaces phenytoin from protein binding site and causes phenytoin toxicity
• Concurrent administration of clonazepam and valproate is contraindicated – absence sz precipitated
• Fetal abnormalities are common when valrpoate & carbamazepine used together
• Sedative - hypnotic- anxiolytic drugs.• MOA
– GABA facilitatory action – Bind to another site on GABA receptor, enhances
presynaptic/ postsynaptic inhibition and ↑ frequency of opening of Cl channel
• Metabolized by liver• Diazepam undergo enterohepatic circulation
Benzodiazepines
Adverse effects of BZD
• Dizziness, vertigo, disorientation, amnesia, prolongation of reaction time
• Weakness, blurring of vision, dry mouth, urinary incontinence
• Aggravate sleep apnoea• Dependence liability is low
Interaction• Synergise with alcohol & other CNS depressants• Concurrent use with valproate- psychotic symptoms
Ethosuximide
• Raises sz threshold • Blocks Ca++ currents (T-currents) in the
thalamus.• Not effective in other seizure types
Adverse effects- • GI complaints most common• CNS effects: drowsiness lethargy• Hypersensitivity rxns are rare
Phenobarbital
• The only barbiturate with selective anticonvulsant effect.
• MOA-– Bind at allosteric site on GABA receptor and ↑ duration of
opening of Cl channel.– ↓ Ca-dependent release of neurotransmitters at high doses.– raises sz threshold
Adverse Effects-• Behavioral abnormalities• Diminution of intelligence• Impairment of learning and memory • Rashes, megaloblastic anaemia, osteomalcia
Interactions
• Induce metabolism of steroids – contraception failure, warfarin
• Synergistic effect wit alcohol and other CNS depressant
• Valproate increases concentration of phenobarbitone
• Gabapentin: Developed as GABA analogue. Mechanism: Increases release of GABA by unknown mechanism.
• Vigabatrin: Irreversible inhibitor of GABA transaminase. Potential to cause psychiatric disorders (depression and psychosis).
• Tiagabine: decreases GABA uptake by neuronal and extraneuronal tissues.
Enhancers of GABA Transmission
Other Na Channel Blockers
• Carbamazepine: may have adrenergic mechanism as well. Serious hematological toxicity: aplastic anemia. Antidiuretic effect (anti ADH).
• Also for trigeminal neuralgia• Lamotrigine: possible other mechanisms.
Effective in Absence seizures and has antidepressant effects in bipolar depression. No chronic associated effects.
Other Drugs
• Topiramate; multiple mechanisms of action (Na channel, GABA enhancement like BZD, antagonist at AMPA subtype of glutamate receptors (not NMDA).
• Felbamate: multiple mechanisms: Na channel block; modulates glutamate transmission interacts with glycine site. Serious hematological and hepatic toxicities.
Non - convulsive SE ?
• Neurologic signs after termination of SE are common:– Pupillary changes– Abnormal tone– Babinski– Posturing– Clonus– May be asymmetrical
Non - convulsive SE ?
• If patient does not begin to respond to painful stimuli within 20 - 30 minutes after tonic - clonic SE, suspect non - convulsive SE– Urgent EEG
Conditions mimicking seizures
• Syncope• Hypoglycemic attacks• TIA• Panic attacks• Physiological jerks during sleep• Breath holding spells in children• Psycogenic ( hysterical) episodes
Syncope v/s seizures
Features syncope seizuresPrecipitating factors common rare
occurence Awake, mostly when upright Awake or sleep
Premonition( nausea,sweating, light Headedness)
Common Uncommon
Onset Less abrupt Abrupt
Jerking of limbs Occasional Frequent
Incontinence Rare Common
Post-ictal recovery Rapid Slow
Post-ictal confusion Uncommon Common
EEG Usually normal May be abnormal
Psychogenic episodes v/s seizures
features Psychogenic episode seizures
Age and gender Young, more in women Any age
Precipitating factors Emotional disturbances Lack of sleep, poor drug compliance
Occurs in sleep No Yes
Duration Minutes to hours Seconds to minutes
movements Vocalization, pelvic thrust, bizzare flinging of limbs
Tonic or tonic clonic jerks
eyes Forcibly close, resistance to opening open
Injuries, including tongue infrequent frequent
Post-ictal confusion, headache,sleep
Uncommon Common
Patterns of attacks Variable stereotyped
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