NEUROLOGY

What do you need to monitor the risk of when taking regular antiplatelets post stroke?

• Helicobacter Pylori… H. Pylori

• Need to test and treat for H.pylori in pts with Hx of ulcer disease or upper GI bleed when on antiplatelets

• Tx = triple therapy with PPI eg omeprazole, lans AND 2 Abx - clarithromycin, metronidazole OR quinolone

What PPI & antiplatelet should never be see together and why?

• clopidogrel and omeprazole as omeprazole inhibits CYP2C19 => blocks conversion of clop into its ACTIVE form so decreased anti clotting ability => increase clot risk

• Alternative to ome = pantoprazole, lansoprazole OR H2 blockers eg famotidine

What are the different types of stroke?

• Ischaemic stroke: clot (blood or atherosclerosis - fatty deposits reducing blood flow) blocking blood vessel, cutting off blood supply to the brain

• Transient ischaemic stroke: AKA ‘mini stroke’. neurological dysfunction causing symptoms lasting few minutes or hours

• haemorrhagic stroke: weakened blood vessels that rupture, causing bleeding in the brain - SUB = surface. INTRA = inside

What are ischaemic stroke symptoms?

• BE FAST:

• Balance lost

• Etes blurred

• Face drooping

• Arms weak

• Speech slurred

• Time to call 999

diff diagnosis = hypoglycaemia, CNS infection, alcohol toxicity

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What is initial management of TIA (NIHSS <4) ?

Stroke within 24hrs:

• Aspirin 300mg STAT + Clopidogrel 300mg STAT

• Clop 300mg STAT alone, if Asp not tolerated

• Tica 180mg STAT dose also an option

What is long term treatment POST TIA?

• After STAT doses, DAPT (Asp 75mg + Clop 75mg OD) to continue for 3 weeks THEN Clop 75mg OD lifelong

• Can also use Ticgrelor 90mg BD if Clop not tolerated

What is initial treatment of an ischaemic stroke (NIHSS >4) ?

IF ISCHAEMIC STROKE CONFIRMED WITHIN 4.5HRS OF SYMPTOM ONSET + IMAGING TO RULE OUT INTRACRANIAL HAEMORRHAGE:

• Thrombolysis with Alteplase (900mcg/kg. MAX dose 90mg) or Tenecteplase (also dosed by weight under specialist)

• Thromboectomy: can be performed within 24hrs of symptom onset BUT do not hold thrombolysis waiting for CT scan to confirm thromboectomy

• Can also jump straight to STAT Asp 300mg if above options no feasible

What comes after thrombolysis in ischaemic stroke?

Re-scan MRI/CT after 24hrs of thrombolysis then an commence antiplatelet

IF NO AF:

• Aspirin 300mg for 2 weeks

• Clop 75mg OD lifelong thereafter

IF with AF:

• Asp 300mg 24hrs after thrombolysis

• Then between days 3 & 12, depending on expert input, restart anticoagulant.

Anticoagulants:

• Apixaban 5mg BD (reduce to 2.5mg BD in pts with at least TWO of: >80 years, <60kg, SrCr >133mmol/L)

• Edoxaban: <61kg = 30mg OD. >61kg = 60mg OD

• Warfarin if CrCl <15mL/min

What are supporter meds POST TIA or stroke

• PPI to reduce GI bleeding while on DAPT: lansoprazole 30mg OD

• Statin: minimum Ator 40mg for 2ndary prevention, can go up to 80mg (high intensity)

Post stroke monitoring?

Continue existing anti-hypertensives & watch BP:

• If thrombolysed, BP must be <185/110 during intial 24hrs - consider labetalol infustion if BP rises tooo much.

• NON thrombolysed BP target = <220

• Long-term BP target after initial highs; AND TDM = <130/80

• Options = thiazide-like diuretic, long-acting calcium-channel blocker, ACEi, ARBs NOT beta blockers (inefficient)

• Aim for blood glucose of 4-11mmol/L post stroke

• Replace Vit D if <50mmol/L

• STOP any HRT/ combined oral contraceptions post stroke, as can trigger another stroke

How are Intracerebral haemorrhages treated?

• Do NOT give BP lowering meds in pt with GCS score <6 or underlying structural cause… poor prognosis

• CAN give rapid BP lowering meds if pts DO NOT fit exclusion criteria AND present with symptoms within 6hrs with systolic BP between 150 & 220

• Aim for BP 130-139 within 1 hr and sustained for at least 7 days, should not drop to 60 within 1hr os starting rapid BP lowering meds

• Must STOP & reverse an anti-coagulation for AF pts presenting with IH… dont want to increase bleeding

Do you given VTE proph to stroke pts?

• NO LMWH eg dalteparin (Fragmin) for stroke pt as run the risk of Haemorrhagic transformation

• Do NOT given compression socks for same reason, use IPCs (intermediate pneumatic compression) instead

which AEDs are given OD when others are usually BD?

• lamotrigine

• perampanel

• phenobarbital

• phenytoin

all have long half-lives => can be given OD at bedtime

how to manage seizures if monotherapy is unsuccessful?

• check the diagnosis before trying monotherapy with an alternative drug

• cross taper the old drug with the new drug

• combo of 2 or more AED may be used but increases risk of S/E and drug interaction

• if combo Tx not working, revert to regimen that provided best balance of tolerability and efficacy

do AEDs need routine plasma conc monitoring?

• not usually needed but may be used in pts with uncontrolled seizures, poor adherence to meds, lots of S/E, or if they have morbidity eg renal failure or if pregnant

when would it be safe to consider withdrawing AED from pt?

• if they have been seizure free for more >2 years

• assessment to carry out risk of seizure reoccurrence must be done

• if on several AEDs, must withdraw meds one at a time

which AEDs should NEVER be abruptly stopped?

• technically ALL of them

• but particularly barbiturates and benzodiazepines; risk of rebound seizures

how long should AED withdrawal take?

• at least 3 months; barbiturates and benzodiazepines may take longer

what to do if pt has seizure shortly during or after stopping AEDs?

• the last dose reduction should be reversed and seek guidance from from epilepsy specialist

what is MHRA advice for AEDs?

• valproate containing meds should NOT be initiated in males or females under 55 unless TWO specialists have agreed and documented that no other Tx is effective or tolerated

• if valporate is offered to females of child-bearing age, risks should be discussed; The Pregnancy Prevention Programme (PPP) should be implemented

• all males on valproate should use condoms (plus contraception used by female partner) during Tx and for 3 months after stopping Tx

• topiramate must not be used in females of child-bearing age unless the PPP are met

• Topiramate not appropriate in pregnant women unless no other suitable drugs

what are risks of using AEDs in pregnancy?

• risk of teratogenicity, birth defects'; spina bifida, cleft palate

• adverse effects on neurodevelopment

which AEDs are safe to use in pregnancy?

1. Lamotrigine; long half life => OD

2. Levetiracetam

ideally monotherapy and lowest dose

what to consider for young woman using hormonal contraceptive and AEDs?

• some AEDs may reduce efficacy of hormonal contraceptive => increased risk of unplanned pregnancy

• HOWEVER, some hormonal contraceptives can also reduce the efficacy of AEDs => increased seizures

what is the likelihood of a female taking AEDs having a baby with no malformations?

• approx. 90%

• encourage folate supplementation while preggers; reduces risk of spina bifida

what should pregnant pts who have seizures in second half of pregnancy (~ weeks 21–40) be assessed for?

• eclampsia - sudden seziures/convulsions, vision changes, severe headaches

• could be sign of untreated preeclampsia; high BP after 20 weeks

can women taking AEDs breast-feed?

• yes it is encouraged

• infants should be monitored for sedation, feeding difficulties, adequate weight gain and developmental milestones

which AEDs are transferred in breastmilk => high infant serum-drug conc?

• newer ones; ethoosuximide, lamotrigine, primidone, and zonisamide

what AEDs have slower metabolism => increased risk of passing onto infant in breastmilk?

• lamotrigine, phenytoin, phenobarital, perampanel

which AEDs cause infant drowsiness through breastmilk?

• primidone

• phenobarbital

• benzos

can infants have withdrawal effects if mum suddenly stops breastfeeding while on AED?

• yes; esp if mum is taking lamotrigine, phenobarbital or primidone

what is MHRA warning for AEDs and thoughts and behaviour patterns?

• small increased risk of suicidal thoughts and behaviour; can commence as early as 1 week after starting Tx

• pts should not stop or switch AED Tx until seek advice from HCP

what does the advice on switching AEDs relate to and NOT relate to in terms of indications?

• MHRA advises that switching AEDs guidance is only recommended for Tx of epilepsy NOT other indications eg mood stabilisation, neuropathic pain

What are the different categories of AEDs and which are appropriate to be switched?

Category 1: CP3; carbemazepine, phenobarbital, phenytoin, primidone; MUST be brand specific

Category 2: clobazam, clonazepam, lamotrigine, oxcarbazepine, perampanel, rufinamide, topiramate, valproate, zonisamide; switching based on clinical judgement and consult with pt and or carer the risks of switching

Category 3: brivaracetam, ethosuximide, gabapentin, lacosamide, levetiracetam, pregabalin, tiagabine, vigabatrin; can be any brand

what is antiepileptic hypersensitivity syndrome and symptoms?

• rare but potentially fatal drug-induced Rx occurring 1-8 weeks after starting aromatic anticonvulsants eg carbamazepine, lacosamide, lamotrigine, oxcarbazepine, phenobarbital, phenytoin, primidone, and rufinamide

• symptoms = fever, rash, lymphadenopathy, liver and renal dysfunction

• pt should NOT be re-exposed to that AED

who must drivers inform if they have a seizure?

• the Driver and Vehicle Licensing Agency (DVLA)

how long should a pt not drive for after having an unprovoked epileptic seizure?

• 6 months; provided they have been assessed and are deemed fit to drive again

when is it safe for someone with established epilepsy drive?

• must be seizure-free for at least ONE year; and no Hx of unprovoked seizures

how long do pts who have had seizures in sleep have to be off the road?

ONE year from the date of sleep seizure unless:

• Hx or pattern of sleep seizures occurring ONLY ever while asleep over a year from the first sleep seizure

• pattern on purely asleep seizures over THREE years if pt previously had awake or asleep seizures

ie can drive if you have sleep seizures, not awake, when driving seizures

what do DLVA recommend to epileptic pts changing or withdrawing AEDs?

• pts should not drive during AED changes or withdrawals and for 6 months after last dose (of reduction regimen)

how long is a driving license revoked for after seizure after AED change or withdrawal?

• revoked for ONE year; relicensing may be considered earlier if Tx restarted for 6 months and pt is seizure free

what are focal seizures w/wo secondary generalisation?

• focal = starts on one side of the brain; can be with preserved consciousness ie pt is awake and aware of seizure OR impaired consciousness ie pt is confused and unaware of seizure

• focal seizures can become generalised ie spread to other side of brain - focal to bilateral generalised tonic-clonic seizure; pt usually have aura before this type of seizure so can prepare

how are focal seizures w/wo secondary generalisation treated?

1st line:

• lamotrigine or levetiracetam

2nd line:

• carbamazepine, oxcarbazepine (better tolerated, few S/Es) OR zonisamide

3rd line:

• lacosamide

what are generalised seizures and examples?

• seizures which affect both sides of the brain

examples

• absence seizures - short period of blanking out or staring into space; pt can miss this seizure even happening;

• atonic seizures - muscles become limp, pt suddenly drops;

• generalised tonic-clonic seizures - starts on one side (focal), then becomes generalised, i.e., spreads to both side of brain => body stiff (tonic) and rhythmic jerking (clonic)

what are adjunctive Tx for focal seizures with or without secondary generalisation

if monotherapy is unsuccessful, consider adding adjuncts:

1st line:

• carbamazepine, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, topiramate, or zonisamide.

2nd line:

• brivaracetam, cenobamate (always used as adjunct, rarely alone), eslicarbazepine acetate, perampanel, or pregabalin.

3rd line:

• phenobarbital, phenytoin, sodium valproate, tiagabine, or vigabatrin.

what is Tx for tonic-clonic generalised seizures?

1st line =

• lamotrigine, levetiracetam, sodium valproate

if monotherapy is unsuccessful, consider adjunct Tx:

1st line =

• clobazam, lamotrigine, levetiracetam, perampanel, sodium valproate OR topiramate

2nd line =

• brivaracetam, lacosamide, phenobarbital, primidone OR zonisamde (all UNLICENSED use)

what is Tx for generalised absence seizures?

1st line:

• ethosuximide

2nd line:

• lamotrigine, levetiracetam (unlicensed use) OR sodium valproate

like I’m in a S(H)ELL, absent from everyone

what AEDs may cause seizure exacerbation in absence seizures?

• carbamazepine, gabapentin, oxcarbazepine, phenobarbital, phenytoin, pregabalin, tiagabine, or vigabatrin

what are myoclonic seizures and how are they treated?

• shock like, forceful jerking seizures

1st line =

• levetiracetam (unlicensed use) or sodium valproate

adjunct therapy if monotherapy is unsuccessful:

• brivaracetam (unlicensed use), clobazam, clonazepam, lamotrigine, phenobarbital, piracetam, topiramate (unlicensed use) OR zonisamide (unlicensed use)

which AEDs may exacerbate myoclonic seirzures?

• carbamazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin, tiagabine, or vigabatrin AND Lamotrigine

what is the over-simplified MoA of AEDs?

• reduce neuronal excitability by blocking sodium channels, enhancing GABA (inhibitory) activity, and reducing glutamate (excitatory) activity.

what type of seizures are mostly seen in children?

• atonic or tonic seizures; associated with learning disabilities or cerebral damage

how are atonic or tonic seizures treated?

1st line:

• lamotrigine or sodium valproate

adjunct therapy if monotherapy is unsuccessful:

1st line

• clobazam, rufinamide (unlicensed use) OR topiramate (unlicensed use)

what are idiopathic generalised epilepsies?

• epilepsy starting in childhood or adolescence; presumed to be genetic rather than due to brain lesions or structural abnormalities

1st line:

• lamotrigine, levetiracetam OR sodium valproate

2nd line adjunct Tx:

• perampanel OR topiramate

what is Drevet syndrome and how is it treated?

• hard to treat developmental and epileptic encephalopathy that begins in infancy

1st line:

• sodium valproate; inc females - best Tx for this indication according to research

1st line adjunct therapy: triple therapy with SV, clobazam and stiripentol

2nd line adjunct therapy: cannabidiol with clobazam, or fenfluramine

3rd line: potassium bromide (unlicensed use)

what AEDs may exacerbate Dravet syndrome?

• carbamazepine, gabapentin, lacosamide, lamotrigine, oxcarbazepine, phenobarbital, pregabalin, tiagabine, or vigabatrin.

what is lennox-gastuat syndrome and how is it treated?

• severe childhood onset epilepsy; multiple Tx-resistant seizure; cognitive impairment

1st line =

• SV inc females

2nd line/ adjunct = lamotrigine

3rd line = cannabidiol with clobazam, fenfluramine, clobazam, rufinamide, or topiramate

what AEDs may exacerbate Lennox-Gastaut syndrome?

• carbamazepine, gabapentin, lacosamide, lamotrigine (even though 2nd line?), oxcarbazepine, phenobarbital, pregabalin, tiagabine, or vigabatrin

what is the term used for seizure > 5mins and how to treat?

• status epilepticus => buccal midazolam OR clobazam, call 999

what are febrile convulsions and Tx?

• seizures esp in young children (6months to 5 years) caused fever

• brief febrile convulsions do not need specific Tx BUT antipyretic eg paracetamol used to reduce fever and prevent further convulsions

• if >5mins, treat as status epilepticus

what is a shared S/E of most AEDs?

• Stevens-Johnson syndrome; due to formation of reactive metabolites => activate the immune system to attack skin => painful blistering of skin and mucous membranes, rash, flu-like symptoms

how do most AEDs affect sodium and potassium levels?

• some AEDs increase ADH (SIADH) => body retains more water => sodium gets diluted => hyponatraemia

• K mostly stays the same

what is SV contraindicated with?

• Acute porphyrias; body doesn’t make enough haem => buildup of chemical toxins => nerve damage; SV can increase production of porphyrins, which can trigger an acute attack.