Chapter 4 – The Nervous System
CHM/MHRA – increased risk of stroke and
Chapter 4 – The death when APs are used in elderly with
Nervous System dementia. Hence, consider risks like H/O
stroke or TIA, HT, DM, smoking and AF
Use at lowest effective dose for shortest
DEMENTIA
time possible (review every 6 weeks)
Define – progressive syndrome In non-Alzheimer’s dementia, APs can
characterised by memory loss, problems worsen motor functions
with reasoning and communication, change 2. Depression and anxiety – CBT or relaxation.
in personality and reduced ability to carry Use ADs for severe problems
out daily activities. 3. Sleep disturbances – sleep hygiene, daylight
Causes = Alzheimer’s (most common type), exposure and increase exercise
vascular dementia (due to cerebrovascular
disease), dementia with Lewy bodies, mixed
EPILEPSY
dementia and frontotemporal dementia Choosing AED – consider epilepsy syndrome,
Tx aims = promote independence, maintain seizure type, other meds, co-morbidity, age, sex
function and manage symptoms
AEDs with a long t½ (ON dose) = lamotrigine,
Treatment Options phenytoin, perampanel, phenobarbital
Mild-to-mod dementia presenting with CAT 1 - maintain on specific brand or generic
cognitive symptoms = structured group CZP, phenobarbital, phenytoin, primidone
cognitive stimulation, group reminiscence
therapy, cognitive rehab, occupational therapy CAT 2 - based on clinical judgement, meeting
with Pt, seizure frequency, Tx history
Cognitive symptoms (Alzheimer’s): Clobazam, clonazepam, eslicarbazepine,
1. 1st line in mild-to-mod Alzheimer’s = lamotrigine, oxcarbazepine, perampanel,
donepezil, galantamine or rivastigmine rufinamide, topiramate, valproate,
2. If anticholinesterases are not tolerated = zonisamide
memantine (preferred in mod-severe AD)
Minimise use of anti-muscarinics CAT 3 - no need to maintain specific product
(antidepressants, antihistamines, Brivaracetam, ethosuximide, gabapentin,
antipsychotics and urinary antispasmodics) lacosamide, levetiracetam, pregabalin,
to reduce cognitive impairment tiagabine, vigabatrin
Avoid stopping acetylcholinesterases (based Antiepileptic Hypersensitivity Syndrome –
on disease severity alone) due to risk of associated with CZP, lacosamide, lamotrigine,
substantial worsening of cognitive function oxcarbazepine, phenobarbital, phenytoin,
Non-Alzheimer’s dementia: primidone, rufinamide (lower risk with
1. Dementia with Lewy bodies, vascular eslicarbazepine, stiripentol, zonisamide)
dementia, Parkinson’s disease dementia Symptoms start between 1-8 weeks of
= donepezil (1st line), galantamine, exposure; fever, rash, lymphadenopathy,
rivastigmine or memantine (2nd line) multi-organ failure, liver dysfunction,
Non-cognitive symptoms: vasculitis, haematological, renal and
1. Agitation, aggression, distress or psychosis – pulmonary abnormalities
also offer APs if Pt is at risk of harm Withdraw ASAP and do not re-expose
,Chapter 4 – The Nervous System
Risk of suicidal thoughts – seek advice if Pt Folate supplements are advised, before
develops mood changes, distress, etc conception and during 1st trimester, to
reduce risk of neural tube defects
Withdrawal – avoid abruptly due to risk of
Adjust doses of phenytoin, CZP and
severe, rebound seizures. If receiving multiple
lamotrigine based on [plasma-drug]
AEDs, withdraw one drug at a time
Monitor foetal growth in Pts taking
Driving – if a seizure occurs, stop driving ASAP levetiracetam and topiramate
and inform DVLA. Women who have seizures in the 2nd half of
Avoid driving for 6 months after Pt has their the pregnancy should be assessed for
1st unprovoked epileptic seizure or a single eclampsia before changing AED Tx
isolated seizure. Routine injection of vitamin K at birth
To continue driving, Pt must be seizure-free reduces risk of neonatal haemorrhage
for at least 1 year, have a pattern of seizures BZPs and phenobarbital are likely to cause
where there’s no influence on their withdrawal effects in newborn
consciousness or ability to act and not have All pregnant women with epilepsy
a H/O unprovoked seizures (regardless of whether they’re taking AEDs)
Pts who’ve had a seizure while asleep are should notify the UK Epilepsy and
not allowed to drive for 1 year from the Pregnancy Register
date of each seizure unless;
Breast-feeding
1. a history or pattern of sleep seizures
If taking 1 AED, encourage BF. If taking >1 or
occurring only ever while asleep has
as a premature birth, seek specialist advice
been proven over at least 1 year from
Monitor all infants for sedation, feeding
the date of 1st sleep seizure; or
difficulties, adequate weight gain, ADRs
2. a proven pattern of only asleep seizures
from AEDs and developmental milestones
is proven over 3 years if Pt has H/O
If toxicity occurs, start formula feeds wean
seizures whilst awake (+/- asleep)
infant off breast-milk to reduce exposure
Avoid driving during AED changes or
withdrawal and for 6 months after last dose AEDs readily
Ethosuximide, Lamotrigine,
If seizure occurs due to AED change or transferred
Primidone, Zonisamide
withdrawal, revoke license for 1 year; into breast-milk
consider re-licensing earlier if Tx has been Lamotrigine
AEDs that accumulate due to
reinstated for 6 months and no further Phenobarbita
slow metabolism in infant
seizures have occurred l
BZPs
Pregnancy AEDs linked with drowsiness Primidone
Valproate has the highest risk of serious in infants Phenobarbita
developmental disorders (30-40% risk) and l
congenital malformations (10% risk) Lamotrigine
AEDs likely to cause
Other drugs with teratogenicity risk = Phenobarbita
withdrawal effects in infant
phenytoin, primidone, lamotrigine, CZP l
due to sudden cessation
Topiramate – increased risk of congenital Primidone
malformations (incl. cleft palate, Treatment Options
hypospadias) if taken in 1st trimester
Risk of harm to mother and foetus from Focal seizures (+/- 2° generalisation)
convulsive seizures > continued therapy 1. Carbamazepine or lamotrigine
Avoid stopping Tx due to risk to foetus
, Chapter 4 – The Nervous System
2. Levetiracetam, oxcarbamazepine, valproate 3. IV lorazepam – if seizure lasts >5 mins.
Repeat once after 10mins if seizures recur
3. CZP, clobazam, gabapentin, lamotrigine, 4. IV diazepam – risk of thrombophlebitis
levetiracetam, oxcarbamazepine, valproate, 5. Rectal diazepam or midazolam oromucosal
topiramate solution – where facilities for resuscitation
Tonic-clonic seizures are not immediately available
1. Valproate or lamotrigine 6. If, after Tx with BZPs, seizure recur or fail to
2. CZP, oxcarbamazepine respond 25mins after onset – phenytoin
3. Clobazam, levetiracetam, topiramate (slow IV injection) or phenobarbital
7. If (6) fails to control seizures 45mins after
Absence seizures onset – anaesthesia with thiopental,
1. Ethosuximide or valproate midazolam or propofol
2. Lamotrigine
3. Clobazam, clonazepam, levetiracetam, Febrile convulsions = anti-pyretic
topiramate, zonisamide Prolonged febrile convulsions (>5mins) or
4. AVOID CZP, gabapentin, oxcarbazepine, recurrent febrile convulsions = treat actively
phenytoin, pregabalin, tiagabine, vigabatrin
ATTENTION DEFICIT HYPERACTIVITY
Myoclonic seizures
DISORDER (ADHD)
1. Valproate
2. Topiramate or levetiracetam Define – behavioural disorder characterised
3. Clobazam, clonazepam, zonisamide by hyperactivity, impulsivity and inattention
4. AVOID CZP, gabapentin, oxcarbazepine, leading to functional impairment.
phenytoin, pregabalin, tiagabine, vigabatrin Symptoms usually occur in ages 3-7 years
but may not be recognised till >7 years
Generalised tonic-clonic seizures that co-exist
More common in males
with myoclonic seizures in idiopathic epilepsy
Inattentive symptoms usually persist unlike
1. Valproate or levetiracetam
hyperactive-impulsive symptoms
Atonic and tonic seizures Associated with oppositional defiant
1. Valproate or lamotrigine disorder (ODD), conduct disorder and mood
2. Rufinamide or topiramate disorders like anxiety, mania, depression
3. AVOID CZP, gabapentin, oxcarbazepine, and substance misuse
pregabalin, tiagabine, vigabatrin Tx aims = reduce functional impairment and
symptoms and improve quality of life
Dravet syndrome = valproate or topiramate
Non-drug Tx = balanced diet, good nutrition
Lennox-Gastaut syndrome = valproate or
and regular exercise.
lamotrigine
Other options include environmental
Epilepsy associated with menstruation =
changes to lighting, noise, reducing
acetazolamide
distractions and reinforcing verbal requests
Status epilepticus with written instructions.
Position Pt to avoid injury CBT is effective in Pts refusing drug Tx, etc
Support respiration by providing oxygen
Drug Tx
Maintain BP and correct hypoglycaemia
1. Methylphenidate or lisdexamfetamine
1. IV thiamine – if alcohol abuse suspected
2. If no improvement within 6 weeks – switch
2. Pyridoxine – if caused by low pyridoxine
to the alternative 1st line drug
CHM/MHRA – increased risk of stroke and
Chapter 4 – The death when APs are used in elderly with
Nervous System dementia. Hence, consider risks like H/O
stroke or TIA, HT, DM, smoking and AF
Use at lowest effective dose for shortest
DEMENTIA
time possible (review every 6 weeks)
Define – progressive syndrome In non-Alzheimer’s dementia, APs can
characterised by memory loss, problems worsen motor functions
with reasoning and communication, change 2. Depression and anxiety – CBT or relaxation.
in personality and reduced ability to carry Use ADs for severe problems
out daily activities. 3. Sleep disturbances – sleep hygiene, daylight
Causes = Alzheimer’s (most common type), exposure and increase exercise
vascular dementia (due to cerebrovascular
disease), dementia with Lewy bodies, mixed
EPILEPSY
dementia and frontotemporal dementia Choosing AED – consider epilepsy syndrome,
Tx aims = promote independence, maintain seizure type, other meds, co-morbidity, age, sex
function and manage symptoms
AEDs with a long t½ (ON dose) = lamotrigine,
Treatment Options phenytoin, perampanel, phenobarbital
Mild-to-mod dementia presenting with CAT 1 - maintain on specific brand or generic
cognitive symptoms = structured group CZP, phenobarbital, phenytoin, primidone
cognitive stimulation, group reminiscence
therapy, cognitive rehab, occupational therapy CAT 2 - based on clinical judgement, meeting
with Pt, seizure frequency, Tx history
Cognitive symptoms (Alzheimer’s): Clobazam, clonazepam, eslicarbazepine,
1. 1st line in mild-to-mod Alzheimer’s = lamotrigine, oxcarbazepine, perampanel,
donepezil, galantamine or rivastigmine rufinamide, topiramate, valproate,
2. If anticholinesterases are not tolerated = zonisamide
memantine (preferred in mod-severe AD)
Minimise use of anti-muscarinics CAT 3 - no need to maintain specific product
(antidepressants, antihistamines, Brivaracetam, ethosuximide, gabapentin,
antipsychotics and urinary antispasmodics) lacosamide, levetiracetam, pregabalin,
to reduce cognitive impairment tiagabine, vigabatrin
Avoid stopping acetylcholinesterases (based Antiepileptic Hypersensitivity Syndrome –
on disease severity alone) due to risk of associated with CZP, lacosamide, lamotrigine,
substantial worsening of cognitive function oxcarbazepine, phenobarbital, phenytoin,
Non-Alzheimer’s dementia: primidone, rufinamide (lower risk with
1. Dementia with Lewy bodies, vascular eslicarbazepine, stiripentol, zonisamide)
dementia, Parkinson’s disease dementia Symptoms start between 1-8 weeks of
= donepezil (1st line), galantamine, exposure; fever, rash, lymphadenopathy,
rivastigmine or memantine (2nd line) multi-organ failure, liver dysfunction,
Non-cognitive symptoms: vasculitis, haematological, renal and
1. Agitation, aggression, distress or psychosis – pulmonary abnormalities
also offer APs if Pt is at risk of harm Withdraw ASAP and do not re-expose
,Chapter 4 – The Nervous System
Risk of suicidal thoughts – seek advice if Pt Folate supplements are advised, before
develops mood changes, distress, etc conception and during 1st trimester, to
reduce risk of neural tube defects
Withdrawal – avoid abruptly due to risk of
Adjust doses of phenytoin, CZP and
severe, rebound seizures. If receiving multiple
lamotrigine based on [plasma-drug]
AEDs, withdraw one drug at a time
Monitor foetal growth in Pts taking
Driving – if a seizure occurs, stop driving ASAP levetiracetam and topiramate
and inform DVLA. Women who have seizures in the 2nd half of
Avoid driving for 6 months after Pt has their the pregnancy should be assessed for
1st unprovoked epileptic seizure or a single eclampsia before changing AED Tx
isolated seizure. Routine injection of vitamin K at birth
To continue driving, Pt must be seizure-free reduces risk of neonatal haemorrhage
for at least 1 year, have a pattern of seizures BZPs and phenobarbital are likely to cause
where there’s no influence on their withdrawal effects in newborn
consciousness or ability to act and not have All pregnant women with epilepsy
a H/O unprovoked seizures (regardless of whether they’re taking AEDs)
Pts who’ve had a seizure while asleep are should notify the UK Epilepsy and
not allowed to drive for 1 year from the Pregnancy Register
date of each seizure unless;
Breast-feeding
1. a history or pattern of sleep seizures
If taking 1 AED, encourage BF. If taking >1 or
occurring only ever while asleep has
as a premature birth, seek specialist advice
been proven over at least 1 year from
Monitor all infants for sedation, feeding
the date of 1st sleep seizure; or
difficulties, adequate weight gain, ADRs
2. a proven pattern of only asleep seizures
from AEDs and developmental milestones
is proven over 3 years if Pt has H/O
If toxicity occurs, start formula feeds wean
seizures whilst awake (+/- asleep)
infant off breast-milk to reduce exposure
Avoid driving during AED changes or
withdrawal and for 6 months after last dose AEDs readily
Ethosuximide, Lamotrigine,
If seizure occurs due to AED change or transferred
Primidone, Zonisamide
withdrawal, revoke license for 1 year; into breast-milk
consider re-licensing earlier if Tx has been Lamotrigine
AEDs that accumulate due to
reinstated for 6 months and no further Phenobarbita
slow metabolism in infant
seizures have occurred l
BZPs
Pregnancy AEDs linked with drowsiness Primidone
Valproate has the highest risk of serious in infants Phenobarbita
developmental disorders (30-40% risk) and l
congenital malformations (10% risk) Lamotrigine
AEDs likely to cause
Other drugs with teratogenicity risk = Phenobarbita
withdrawal effects in infant
phenytoin, primidone, lamotrigine, CZP l
due to sudden cessation
Topiramate – increased risk of congenital Primidone
malformations (incl. cleft palate, Treatment Options
hypospadias) if taken in 1st trimester
Risk of harm to mother and foetus from Focal seizures (+/- 2° generalisation)
convulsive seizures > continued therapy 1. Carbamazepine or lamotrigine
Avoid stopping Tx due to risk to foetus
, Chapter 4 – The Nervous System
2. Levetiracetam, oxcarbamazepine, valproate 3. IV lorazepam – if seizure lasts >5 mins.
Repeat once after 10mins if seizures recur
3. CZP, clobazam, gabapentin, lamotrigine, 4. IV diazepam – risk of thrombophlebitis
levetiracetam, oxcarbamazepine, valproate, 5. Rectal diazepam or midazolam oromucosal
topiramate solution – where facilities for resuscitation
Tonic-clonic seizures are not immediately available
1. Valproate or lamotrigine 6. If, after Tx with BZPs, seizure recur or fail to
2. CZP, oxcarbamazepine respond 25mins after onset – phenytoin
3. Clobazam, levetiracetam, topiramate (slow IV injection) or phenobarbital
7. If (6) fails to control seizures 45mins after
Absence seizures onset – anaesthesia with thiopental,
1. Ethosuximide or valproate midazolam or propofol
2. Lamotrigine
3. Clobazam, clonazepam, levetiracetam, Febrile convulsions = anti-pyretic
topiramate, zonisamide Prolonged febrile convulsions (>5mins) or
4. AVOID CZP, gabapentin, oxcarbazepine, recurrent febrile convulsions = treat actively
phenytoin, pregabalin, tiagabine, vigabatrin
ATTENTION DEFICIT HYPERACTIVITY
Myoclonic seizures
DISORDER (ADHD)
1. Valproate
2. Topiramate or levetiracetam Define – behavioural disorder characterised
3. Clobazam, clonazepam, zonisamide by hyperactivity, impulsivity and inattention
4. AVOID CZP, gabapentin, oxcarbazepine, leading to functional impairment.
phenytoin, pregabalin, tiagabine, vigabatrin Symptoms usually occur in ages 3-7 years
but may not be recognised till >7 years
Generalised tonic-clonic seizures that co-exist
More common in males
with myoclonic seizures in idiopathic epilepsy
Inattentive symptoms usually persist unlike
1. Valproate or levetiracetam
hyperactive-impulsive symptoms
Atonic and tonic seizures Associated with oppositional defiant
1. Valproate or lamotrigine disorder (ODD), conduct disorder and mood
2. Rufinamide or topiramate disorders like anxiety, mania, depression
3. AVOID CZP, gabapentin, oxcarbazepine, and substance misuse
pregabalin, tiagabine, vigabatrin Tx aims = reduce functional impairment and
symptoms and improve quality of life
Dravet syndrome = valproate or topiramate
Non-drug Tx = balanced diet, good nutrition
Lennox-Gastaut syndrome = valproate or
and regular exercise.
lamotrigine
Other options include environmental
Epilepsy associated with menstruation =
changes to lighting, noise, reducing
acetazolamide
distractions and reinforcing verbal requests
Status epilepticus with written instructions.
Position Pt to avoid injury CBT is effective in Pts refusing drug Tx, etc
Support respiration by providing oxygen
Drug Tx
Maintain BP and correct hypoglycaemia
1. Methylphenidate or lisdexamfetamine
1. IV thiamine – if alcohol abuse suspected
2. If no improvement within 6 weeks – switch
2. Pyridoxine – if caused by low pyridoxine
to the alternative 1st line drug
