Review of Critical Care Medicine

A seizure (from the Latin sacire, "to take possession of") is a paroxysmal event due to abnormal excessive or synchronous neuronal activity in the brain.

The meaning of the term seizure needs to be carefully distinguished from that of epilepsy. Epilepsy describes a condition in which a person has recurrent seizures due to a chronic, underlying process. This definition implies that a person with a single seizure, or recurrent seizures due to correctable or avoidable circumstances, does not necessarily have epilepsy. Epilepsy refers to a clinical phenomenon rather than a single disease entity, since there are many forms and causes of epilepsy.

Todds paralysis is seen in – (NIMHANS 88)
a) Head injury
b) Strokes
c) Epilepsy
d) Subarachnoid hemorrhage

Seen in Partial/Focal Motor Seizures.

IMPORTANT:-Focal seizures originate within networks limited to one cerebral hemisphere (note that the term partial seizures is no longer used).

Three additional features of focal motor seizures are worth noting:-

1.First, in some patients the abnormal motor movements may begin in a very restricted region such as the fingers and gradually progress (over seconds to minutes) to include a larger portion of the extremity. This phenomenon, described by Hughlings Jackson and known as a "Jacksonian march," represents the spread of seizure activity over a progressively larger region of motor cortex.

2.Second, patients may experience a localized paresis (Todd’s paralysis) for minutes to many hours in the involved region following the seizure.

3.Third, in rare instances the seizure may continue for hours or days. This condition, termed epilepsia partialis continua, is often refractory to medical therapy.

Tic douloureux is synonymous with- (Kerala 91)
a) Trigeminal neuralgia
b) Temporal lobe epilepsy
c) Glossopharyngeal neuralgia
d) Todds paralysis

The most common physical sign of cerebral
metastasis- (Karnat 98)
a) Epilepsy
b) Focal neurological deficit
c) Papilloedema
d) Visual defects

Bano Begum, 45 year old lady has typical hand and limb movements with abnormal smell sensation. She was not able to recall any of the events afterwards.Her most probable diagnosis? (AI 02)

a) Temporal lobe epilepsy b) Dislocation disorder
c) Fugue d) Conversion reaction

MOST IMPORTANT:-The range of potential clinical behaviors linked to focal seizures is so broad that extreme caution is advised before concluding that stereotypic episodes of bizarre or atypical behavior are not due to seizure activity. In such cases additional, detailed EEG studies may be helpful.

Stereotypical :- Designating behaviour which is repeated without variation irrespective of the particular circumstances.

Simple partial seizure is diagnosed by –
a) EEG b) BEAR (NIMHANS 2K)
c) CT scan d) MRI

Drug of choice for simple partial seizure is -(A197)
a) Sodium Valproate b) Carbamazepine
c) Phenobarbitone , d) Diazepam

Ethosuximide is used in the treatment of:
A. Tonic-clonic seizure
B. Absence seizure
C. Myoclonic seizure
D. Simple partial seizure

The drug carbamazepine is used for all except

a) MDP (AIIMS 97)
b) Partial seizures
c) Trigeminal neuralgia
d) Migraine

Carbamazepine (CBZ) is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia. It is also used off-label for a variety of indications, including attention-deficit hyperactivity disorder (ADHD), schizophrenia, phantom limb syndrome, complex regional pain syndrome, paroxysmal extreme pain disorder, neuromyotonia, intermittent explosive disorder, borderline personality disorder and post-traumatic stress disorder.

It has been seen as safe for pregnant women to use carbamazepine as a mood stabilizer, but, like other anticonvulsants, intrauterine exposure is associated with spina bifida and neurodevelopmental problems.

Ethosuximide is used in the treatment of- (AI 06)
a) Tonic-clonic seizure b) Absence seizure
c) Myoclonic seizure d) Simple partial seizure

Mesial temporal lobe epilepsy. The EEG suggested a right temporal lobe focus. Coronal high-resolution T2-weighted fast spin echo magnetic resonance image obtained through the body of the hippocampus demonstrates abnormal high-signal intensity in the right hippocampus (white arrows; compare with the normal hippocampus on the left, black arrows) consistent with mesial temporal sclerosis.

In status epilepticus the drug of choice is –
a) IV Phenytoin (NIMHANS 88)
b) IV ethosuximide
c) IV Phenobarbitone
d) IV diazepam

The duration of seizure activity sufficient to meet the definition of status epilepticus has traditionally been specified as 15–30 minutes. However, a more practical definition is to consider status epilepticus as a situation in which the duration of seizures prompts the acute use of anticonvulsant therapy. For GCSE, this is typically when seizures last beyond 5 minutes.

Status epilepticus is a medical emergency. Initial management includes maintenance of the airway and 50% dextrose (25–50 mL) intravenously in case hypoglycemia is responsible. If seizures continue, an intravenous bolus of lorazepam, 4 mg, is given and repeated once after 10 minutes if necessary; alternatively, 10 mg of diazepam is given intravenously over the course of 2 minutes, and the dose is repeated after 10 minutes if necessary. This is usually effective in halting seizures for a brief period but occasionally causes respiratory depression.

Regardless of the response to lorazepam or diazepam, phenytoin (18–20 mg/kg) is given intravenously at a rate of 50 mg/min; this provides initiation of long-term seizure control. The drug is best injected directly but can also be given in saline; it precipitates, however, if injected into glucose-containing solutions. Because arrhythmias may develop during rapid administration of phenytoin, electrocardiographic monitoring is prudent. Hypotension may complicate phenytoin administration, especially if diazepam has also been given. In many countries, injectable phenytoin has been replaced by fosphenytoin, which is rapidly and completely converted to phenytoin following intravenous administration. No dosing adjustments are necessary because fosphenytoin is expressed in terms of phenytoin equivalents (PE); fosphenytoin is less likely to cause reactions at the infusion site, can be given with all common intravenous solutions, and may be administered at a faster rate (150 mg PE/min). It is also more expensive.

If seizures continue, phenobarbital is then given in a loading dose of 10–20 mg/kg intravenously by slow or intermittent injection (50 mg/min). Respiratory depression and hypotension are common complications and should be anticipated; they may occur also with diazepam alone, although less commonly. If these measures fail, general anesthesia with ventilatory assistance and neuromuscular junction blockade may be required. Alternatively, intravenous midazolam may provide control of refractory status epilepticus; the suggested loading dose is 0.2 mg/kg, followed by 0.05–0.2 mg/kg/h.

After status epilepticus is controlled, an oral drug program for the long-term management of seizures is started, and investigations into the cause of the disorder are pursued.

Diazepam:-Sufficient cerebral levels are reached within one minute of a standard intravenous injection, and rectal administration produces peak levels at about 20 minutes. Diazepam is rapidly redistributed after acute administration, and thus has a relatively short duration of action. After repeated dosing, diazepam accumulates, resulting in higher peak levels, which persist. This can result in sudden and unexpected CNS depression and cardiorespiratory collapse. Diazepam is metabolised by hepatic microsomal enzymes. Respiratory depression, hypotension, and sedation are the principal side effects. Sudden apnoea can occur, especially after repeated injections or if the injection is administered at too fast a rate.

Bolus intravenous doses of diazepam should be given in an undiluted form at a rate not exceeding 25 mg/minute, using the Diazemuls formulation

Lorazepam:- has a lesser volume of distribution and is less lipid soluble than diazepam. Its pharmacokinetic characteristics result in a slower onset of action, but a longer duration of action. Lorazepam is indicated in the early stage of status epilepticus only, where its lack of accumulation in lipid stores, strong cerebral binding, and long duration of action due to its distribution half-life are very significant advantages over diazepam.

Initial injections of lorazepam are effective for about 12 hours (longer than with diazepam), but repeated doses are much less effective, and the drug has no place as long-term therapy.

Lorazepam is administered by intravenous bolus injection. As distribution is slow, the rate of injection is not critical. In adults, a bolus dose of 0.07 mg/kg (to a maximum of 4 mg) is given, and this can be repeated once after 20 minutes if no effect has been observed. In children under ten years, bolus doses of 0.1 mg/kg are recommended. Long-term infusion of lorazepam should not be used. It is usually available as a 1 ml ampoule containing 4 mg of lorazepam.

The initial infusion of phenytoin takes 2030 minutes in an adult, and the onset of action is slow. It is therefore often administered in conjunction with a short-acting drug with a rapid onset of action, such as diazepam

PHENYTOIN:-It is a highly effective anticonvulsant, with the particular advantage of a long duration of action.The usual phenytoin solutions have a pH of 12 and, if added to bags containing large volumes of fluid at lower than physiological pH (for example, 5% glucose), precipitation may occur in the bag or tubing; use in a solution of 0.9% sodium chloride (normal saline) (5-20 mg/ml) is safer. There is also a serious risk of precipitation if other drugs are added to the infusion solution.

The rate of infusion of phenytoin solution should not exceed 50 mg/minute, and it is prudent to reduce this to 2030 mg/minute in the elderly. The adult dose is 1520 mg/kg; this usually amounts to about 1000 mg and therefore takes at least 20 minutes to administer. Regrettably, a common and potentially serious mistake is to give a lower dose which results in suboptimal cerebral levels.

PHENOBARBITONE:-Phenobarbitone is a drug of choice for the treatment of established status epilepticus. It is highly effective, has a rapid onset of action, and prolonged anticonvulsant effects. It has stable and non-reactive physical properties, as well as convenient pharmacokinetics. Wide experience has been gained of its use in adults and in children, and few drugs are as well tried in the newborn. It has stronger anticonvulsant properties than most other barbiturates, and may be preferentially concentrated in metabolically active epileptic foci. As well as excellent anticonvulsant properties, it may also have cerebral-protective action. Acute tolerance to the antiepileptic effect is unusual, in contrast to the benzodiazepines and, once controlled, seizures do not tend to recur. Indeed, there is evidence to suggest that given with barbiturate anaesthesia, it can reduce the relapse rate with anaesthetic withdrawal.
The main disadvantages of phenobarbitone are its potential to cause sedation, respiratory depression, and hypotension; although in practice these effects seem slight except at high levels or with rapidly rising levels, its safety at even high doses is well established. The well-known chronic side effects of phenobarbitone in long-term therapy are of little relevance in the emergency situation of status epilepticus. The drug is eliminated slowly and, although this is of no importance on initial phenobarbitone loading, on prolonged therapy there is a danger of accumulation and blood level monitoring is essential. In the newborn period dosing is more difficult than in adults, as the pharmacokinetics change rapidly during the first weeks and months of life. The drug has a strong tendency to autoinduction. Phenobarbitone is a stable preparation, which does not easily decompose, and the drug is not absorbed by plastic. It should not be used in a solution containing other drugs (for example, phenytoin), as this may result in precipitation.
The usual recommended adult intravenous loading dose of phenobarbitone is 10 mg/kg (doses of up to 20 mg/kg have been used and recommended), given at a rate of 100 mg/minute (i.e. a total of about 700 mg in seven minutes). This should be followed by daily maintenance doses of 1-4 mg/kg. In neonates, initial phenobarbitone loading doses of between 12 and 20 mg/kg have been recommended to produce therapeutic levels, with subsequent supplementation of 3-4 mg/kg per day, to a maximum dose of 40 mg/kg. In older children, loading doses of between 5 and 20 mg/kg are recommended and maintenance doses of 1-4 mg/kg, although much higher doses have been safely given. After loading, maintenance doses can be given by the oral, intravenous, or intramuscular route. Phenobarbitone is usually presented in 1 ml ampoules containing 200 mg of phenobarbitone sodium.

Which of the following is not an adverse effect of
phenytoin – (AI 90)
a) Gum hyperplasia
b) Osteomalacia
c) Gynecomastia
d) Megaloblastic anaemia

In epilepsy, EEG is – (Kerala 90)
a) Diagnostic
b) Useless in diagnosis
c) Complimentary in diagnosis
d) may or may not be useful

Investigation of choice to diagnose epilepsy is –
a) MRI b) EEG (Kerala 94)
c) CT scan d) Angiogram

EEG with spike and dome pattern is characteristic
of…. Epilepsy – (AIIMS 85)
a) Jacksonian b) Grandmal
c) Petitmal d) Temporal lobe

Drug of choice for psychomotor epilepsy is

a) Valproic acid b) Carbamazepine (AIIMS 87) c) Ethosuximide d) Barbiturate
e) Phenytoin

Temporal lobe epilepsy was first recognized in 1881 by John Hughlings Jackson, who described "uncinate fits" seizures arising from the uncal part of temporal lobe and the "dreamy state."

In the 1940s, Gibbs et al introduced the term psychomotor epilepsy.The international classification of epileptic seizures (1981) replaced the term psychomotor seizures with complex partial seizures. Complex means that there is some alteration of consciouness, versus a simple partial seizure, which means there is no alteration of consciouness. The ILAE classification of the epilepsies uses the term temporal lobe epilepsy and divides the etiologies into cryptogenic (presumed unidentified etiology), idiopathic (genetic), and symptomatic (cause known, eg, tumor).

Carbamazepine (or a related drug, oxcarbazepine), lamotrigine and phenytoin are currently the drugs of choice approved for the initial treatment of focal seizures, including those that evolve into generalized seizures. Overall they have very similar efficacy, but differences in pharmacokinetics and toxicity are the main determinants for use in a given patient. For example, an advantage of carbamazepine (which is also available in an extended-release form) is that its metabolism follows first-order pharmacokinetics, and the relationship between drug dose, serum levels, and toxicity is linear. Carbamazepine can cause leukopenia, aplastic anemia, or hepatotoxicity and would therefore be contraindicated in patients with predispositions to these problems. Oxcarbazepine has the advantage of being metabolized in a way that avoids an intermediate metabolite associated with some of the side effects of carbamazepine. Oxcarbazepine also has fewer drug interactions than carbamazepine. Lamotrigine tends to be well tolerated in terms of side effects. However, patients need to be particularly vigilant about the possibility of a skin rash during the initiation of therapy. This can be extremely severe and lead to Stevens-Johnson syndrome if unrecognized and if the medication is not discontinued immediately. This risk can be reduced by slow introduction and titration.

Psychomotor epilepsy is Temporal lobe epilepsy

True about juvenile mycoclonic epilepsy – (PGI 03)
a) Focal seizure
b) Generalised seizure
c) Myoclonus
d) Responses to Sodium Valproate
e) Spike and waves in EEG

All the following are indications for brain imaging
in epilepsy, except – (J & k 05)
a) Epilepsy starts after the age of 5 years
b) Seizures have focal features clinical
c) EEG shows a focal seizure source
d) Control of seizures is difficult

Gustatory hallucinations are most commonly
associated with – (Corned 08)
a) Temporal lobe epilepsy
b) Grand mal epilepsy
c) Anxiety disorders
d) Tobacco dependence

Cause of death which is common in case of coma –
a) Tongue falling back and obstructing airway
b) Secretions obstructing airway (TN 03)
c) Cardiac arrest
d) Epilepsy

1501. Which vitamin deficiency is most commonly seen in a pregnant mother who is on phenytion
therapy for Epilepsy? All India 2006
a) Vitamin B6 b) Vitamin B12 c) Vitamin A d) Folic Acid

In Petit Mal epilepsy all findings are seen except JIPMER ’98
a) Transient loss of conciousness b) Non specific ECG pattern
c) No tonic-clonic phase d) Ethosuccamide is Drug of choice

A 15 year old boy with epilepsy on treatment with
combination of valproate and phenytoin has good
control of seizures. Levels of both drugs are in the
therapeutic range. All of the following adverse effects
can be attributed to valproate except :
A. Weight gain of 5 kg
B. Serum alanine aminotransaminase 150 IU/L
C. Rise in serum ammonia level by 201.tg/dL
D. Lymphadenopathy

Which of the following statements is incorrect in
relation to pregnant women with epilepsy?
A. The rate of congenital malformation is increased
in the offspring of women with epilepsy.
B. Seizure frequency increases in approximately
70% of women.
C. Breast feeding is safe with most anticonvulsants.
D. Folic acid supplementation may reduce the risk of
neural tube defect

An elderly male on ventilator has received atracurium
infusion for 3 days. He now develops epileptic fits.
Probable cause for his epilepsy is:
A. Allergy to drug
B. Accumulation of Atracurium
C. Accumulation of Laudanosine
D. Ventilator failure

Palatal Myoclonus is seen in – (SGPGI 05)
a) Epilepsy
b) Multiple sclerosis
c) Cerebellar infarction
d) Guillain Barre syndrome

Deja Vu is seen in – (Kerala 94)
a) Normal persons b) Temporal lobe epilepsy
c) Psychosis d) All of the above

Arun, diagnosed to have epilepsy recently and put
on phenytoin. He was previously on
antidepressents. He has developed fatigue and
anorexia. His Hb=8.0; TC=7500 ; ESR=30 in first
hour; SGOT=35; SGPT=35 and B-=0.6. the test
for diagnosis would be – (AIDE 99)
a) Chest x-ray b) Urine culture
•c) MCV d) Blood culture

All are used in treatment of epilepsy excepta)
Ethosuximide b) Reserpine (Kerala 94)
c) Acetazolamide d) Vigabatrine

Carbamazepine is useful in the following
conditions EXCEPT- (Kann 95)
a) Grandmal epilepsy b) Petitmal epilepsy
c) Psychomotor epilepsy d) Trigeminal neuralgia

Which is true regarding febrile seizures- (AI 93)
a) 50% recurrance
b) Long term phenytoin required
c) Interictal EEG normal
d) Status epilepsy is common

Hypsarrythmia in a child is due to

a) Grandmal epilepsy (AIIMS 91, Delhi 93)
b) Petitmal epilepsy
c) Myoclonic epilepsy
d) Reflex epilepsy

All of the following are true of febrile seizures except

a) Most commonly seen between 9 months and 5 years (AP 97)
b) Does not last more than 10 minutes
c) Almost invariably develop into epilepsy
d) Prognosis is good

WhIch of the following has the worst
prognosis – (JIPMER 2001)
a) Rolandic epilepsy b) Versive epilepsy
c) Absence epilepsy d) Infantile spasm

Which one of the following in the characteristic
feature of juvenile myoclonic epilepsy ? (AIIMS 06)
a) Myoclonic seizures frequently occur in morning
b) Complete remission is common
c) Response to anticonvulsants is poor
d) Associated absence seizures are present in
majority of patients

A 18-month old baby presents with recurrent
episodes of excessive crying followed by cyanosis,
uncon sciousness and occassional seizures since 9
months of age. The most likely diagnosis
is – (UPSC 98)
a) Epilepsy b) Anoxic spells
c) Breath holding spells d) Vasovagal attack