Seizures and epileptic syndromes long case

Question 1

SCN1A mutations result in which syndrome?

Answer 1

Dravet

Question 2

structural causes of seizure disorders

Answer 2

Malformations (or cortical development, or focal cortical dysplasias), Tuberus Sclerosis complex/tumours/trauma
Vascular malformation/vascular accident (stroke, haemorrhagic or ischaemia)
Hippocampal sclerosis (HS)/Hypothalamic hamartoma/ (HH) / HIE

Question 3

what are the causes of seizure disorders?

Answer 3

Genetic
Structural
Metabolic
Immune causes
Infectious causes

Question 4

immune causes of seizure disorders?

Answer 4

Rasmussen syndrome (seizures involving hemiparesis - treat with immunosuppression, neurosurgical intervention - hemidisconnection), and several rare antibody-mediated conditions including coealiac disease, epilepsy, and cerebral calficiation sundrome.

Question 5

Infectious causes of seizure?

Answer 5

1. meningitis
2. encephalitis
3. cerebral toxoplasmosis
4. cerebral malaria
5. HIV
6. subacute sclerosing panencephalitis (SSPE) and neurocysticercosis

Question 6

Neonatal period seziure disorders

Answer 6

Otahara syndrome (Early Infantile Epileptic Encephalopathy with suppression burst)
- xcauses include Aicardi syndrome (agenesis corpus callosum, inflantile spasms, chorioretinal lacunae)
- focal cortical dysplasia
- cerebral dysgenesis
- STXBP1, which has a broad phenotype (Otahara to dravet)

Question 7

early myoclonic encephalopathy disorders?

Answer 7

IEM (non ketotic hyperglycaemia, menkes, zellweger and MMA)
*assess and treat pyridoxing dependent epilepsy or PNPO

Question 8

Genetic causes of infantile epilepsy?

Answer 8

ERBB4 and SCN1A
Onset is usually before day 10, with the clinical triad: myoclonus (randomly shifting, fragmentary), then focal fits, then tonic (infantile) spasms; devastating psychomotor developmental regression; all have bilateral pyramidal signs.

Question 9

Investigations to exclude metabolic causes

Answer 9

1. glucose / urine metabolic screen
2. UEC, acylcarnitines, ammonia, TORCH screen (inc. CSF), amino acids
3. copper, biotinidase, caeruroplasm, urate

EEG

Question 10

myoclonic encephalopathy in non progressive disorders

Answer 10

Prader-willi, Angelman’s, Wolf-Hirschhorn, RETT, non ketotic hyperglycaemia

Question 11

Wolf-Hirschhorn

Answer 11

Warrior Helmet (facies), intellectual impairment, restricted growth, small head, closure defects (clefts [lip/palate], coloboma of iris, cardiac [ASD, VSD]), hypertelorism, high forehead, high arched eyebrows, ocular findings (protruding eyes, epicanthic folds), retrognathia, nose (beaked, widened, skeletal [scoliosis, kyphosis, dislocatable hips, talipes])

Question 12

Dravet (severe myoclonic epilepsy of infancy)

Answer 12

Chromosome/gene: 2q24.3/SCN1A; Onset average 6 months; can present in status (hemiclonic, general or febrile); can have hemimotor status (but involve other side next time). focal dyscognitive (pallor, automatisms, absence), in clusters, often head turn and flexed upper limbs, mainly myoclonic by 4 years; can have atypical absence seizures, atonic seizures, non-convulsive status; 25% have visual-induced seizures. Exclusionary features: spasms (if patients have spasms, or tonus, then the diagnosis is not Dravet and must be reassessed). Precipitants: hyperthermia, water (bathing), light, CBZ; frequent fits until 12 months, multiple seizure types between 1 and 4, mainly myoclonic by 4; most have normal development initially, but after 12 months.

Ataxia with pyramidal signs;

Question 13

treatment for dravet

Answer 13

AEDs used (suggested sequence): first try valproate, then topiramate, then clobazam, then levetiracetam, then stiripentol (chemically unrelated to other AEDs, approved in Europe for Dravet syndrome as an adjunct to valproate and clobazam). Cannabidiol might decrease seizure frequency in children with treatment-resistant epilepsy

Question 14

what are sodium channel blocking AEDs

Answer 14

Carbamazepine, Rufinamide, Phenytoin, Lamotragine, Oxcarbazepine.

Question 15

West Syndroe

Question 16

West Syndrome

Answer 16

Epileptic encephalopathy with mutliple causes.
- structural - TSC/Aicardi/lissencephaly
- Acquired (pre/peri/post natak cerebral ischaemia/CVA/infections)
- chromosomal abnormalities (Down, Miller-Dieker lissencephalut)

Hypsarrythmia and developmental regression.

Question 17

treatment of West syndrome

Answer 17

AEDs of choice are ACTH, steroids or vigabatrin. If TS is the cause, then vigabatrin is first line; if non-TS, then ACTH or prednisolone are first line

Question 18

Early onset childhood occipital epilepsy (Panayiotopoulos type)

Answer 18

Onset range 1–14 years, peak 4–5 years; autonomic symptoms

Pallor, Nausea, y, Incontinence, Ocular: mydriasis, Tone lost, Prolonged duration, o, Unilateral eye deviation, Limited to under 14 years, o, Salivation [hypersalivation], Syncope-like, Status common.
0 benign prognosis, AED rarely needed.

Question 19

Doose syndrome (epilepsy with myoclonic-atonic) seizures

Answer 19

In two-thirds, febrile and afebrile GTCSs occur initially, months before myoclonic-atonic; all patients have symmetrical myoclonic jerks followed immediately by loss of tone (post-myoclonic inhibition); can also have pure atonic or absence, and non-convulsive (myoclonic-atonic) status (the latter being a frequent feature). photic stimulation can precipitate myoclonic-atonic seizures; non-convulsive status causes repetitive 2–3 Hz spike-wave pattern, can be continuous or discontinuous

Question 20

treatment for doose

Answer 20

valproate, lamotrigine, levetiracetam; occasionally clonazepam, clobazam or nitrazepam. The ketogenic diet has worked better than any AEDs for some patients; a modified Atkins diet can also be helpful

Question 21

Late-onset childhood occipital epilepsy (Gastaut type)

Answer 21

pure occipital seizures, with visual hallucinations (usually small multicoloured circular patterns, compared to ‘fuzzy’ confetti, or sequins), blindness or a combination; short (few seconds to 3 minutes), frequent, often diurnal

Question 22

AEDs of choice for Gastaut

Answer 22

carbamazepine

Question 23

Benign epilepsy with centrotemporal spikes (BECTS)

Answer 23

onset 3–14, peak age 8–9 years, resolution by 13; nocturnal orofaciobrachial focal seizures, short (1–3 minutes), involving the vocal tract, with oropharyngolaryngeal guttural sounds (‘chuggers’ and ‘gluggers’), and hemifacial sensorimotor symptoms that spread to the tongue, mouth and face, causing hypersalivation and speech arrest; consciousness preserved; secondarily GTCSs in 50%. occur during sleep onset or waking;

Question 24

AEDs used in BECTS

Answer 24

carbamazepine, levetiracetam

Question 25

Lennox-Gastaut syndrome (LGS)*

Question 26

encephalopathic continuum

Answer 26

10–30% derive from West syndrome, being the third part of an encephalopathic continuum (mnemonic OWL): Ohtahara to West to LGS

Question 27

tx for lennox gastaut

Answer 27

valproate (beware hepatic failure, acute haemorrhagic pancreatitis)

Question 28

LGS

Answer 28

Tonic, Absence (atypical), Atonic, with polymorphic intractable seizures—tonic (symmetrical, brief [2–10 seconds]), atypical absences (clouding of consciousness, tone changes, myoclonic jerks), atonic (sudden brief [1–2 seconds] loss of postural tone) drop attacks.

Question 29

LGS

Answer 29

Tonic, Absence (atypical), Atonic, with polymorphic intractable seizures—tonic (symmetrical, brief [2–10 seconds]), atypical absences (clouding of consciousness, tone changes, myoclonic jerks), atonic (sudden brief [1–2 seconds] loss of postural tone) drop attacks.

Question 30

Treatment for LGS

Answer 30

2Vs, 2Cs, 2Rs (2VCRs), + 2Ls + Topiramate + Ketogenic diet: Valproate, Vagus nerve stimulation, Clonazepam, Corpus callosotomy, Rufinamide, Resection of focal cortex, Lamotrigine, Levetiracetam, Topiramate. Note also several contraindicated AEDs; carbamazepine, oxcarbazepine, gabapentin, pregabalin, tiagabine (so, in LGS avoid 2 ‘carbs’ and 3 with ‘gab/a’ in name).

Question 31

Absence—childhood absence epilepsy (CAE)

Answer 31

Onset range 2–10 years, peak 5–7 years, more in girls; very frequent (dozens per day) absences; brief (under 20 seconds); abrupt loss of consciousness; may be automatisms

Question 32

treatment for CAE

Answer 32

AEDs of choice: ethosuximide, valproate, lamotrigine. Note contraindicated AEDs: most others; that is, carbamazepine, oxcarbazepine, phenytoin, phenobarbitone—ones with ‘gab/a’ in their name, such as pregabalin, vigabatrin, gabapentin and tiagabine (so, in CAE avoid 2 ‘carbs’, 2 ‘phens’ and all ‘gab/as’)

Question 33

CSWS—epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS)

Answer 33

EEG finding of CSWS, which correlates with encephalopathy developing, has onset 1–2 years after seizures, with a peak of 8 years; seizures may be nocturnal unilateral motor seizures, diurnal absences or atonic; regression of IQ, language, behaviour and psychological state; deficits depend on spike localisation. Frontal lobe targeting leads to disinhibition, aggressiveness, inattention, cognitive decline, psychosis (frontal lobe dementia); temporal lobe involvement causes expressive aphasia. Motor problems: ataxia, hemiparesis, dyspraxia.

Question 34

treatment for CSWS?

Answer 34

Treatment: spike suppression; similar to approach in LKS. AEDs used: valproate with lamotrigine, ethosuximide, clonazepam, clobazam, levetiracetam; if unsuccessful, then ACTH or prednisolone; if intractable deterioration, surgical treatment with multiple subplial intracortical transections can succeed. Prognosis: earlier onset imparts worse prognosis.

Question 35

mesial temporal lobe epilepsy with hippocampal sclerosis

Answer 35

The cause is unknown, although many have an early childhood history of febrile convulsions, head injury, meningoencephalitis or hypoxic insults. This is the commonest epileptic syndrome. Simple focal seizures commence with an ascending epigastric aura, a ‘welling up’ from the stomach; impaired ability to speak, but retained ability to comprehend conversations, last 1–2 minutes;

Question 36

treatment for mesial temporal lobe epilepsy with hippocampal sclerosis

Answer 36

AEDs used are carbamazepine and levetiracetam. Neurosurgical treatment is available if AEDs fail, with anterior temporal lobe resection with hippocampectomy

Question 37

SCN1A-related seizure disorders

Answer 37

smutations in this sodium channel alpha one unit
-dravet; severe myoclonic epilepsy, infantile partial seizures.

• doose, lennox gastaut, vaccine related encephalopathy

Question 38

Treatment of Status epilepticus

Answer 38

IV - midaz x 2, then keppra load, then phenytoin, then rapid sequence induction

IM/PO midaz x 2, then phenobarb, RSI

Question 39

Who does ketogenic diet benefit?

Answer 39

Dravet, Doose, Lennox-Gastaut, Rett, West), metabolic disorders (GLUT1 deficiency, pyruvate dehydrogenase deficiency [PDHD]), and TSC

Question 40

history of seizures

Answer 40

1. The past history of the seizures—in terms of number of hospital admissions, previous anticonvulsants used and why they were changed
2. any previous complications of seizures or their treatment, and whether febrile convulsions occurred at a younger age—should be covered thoroughly.
3. The past history of possible aetiological factors (epilepsy risk factors), such as prematurity, cerebral infection, head injury or other neurological insult, should be sought.
   4 Note any family history of seizure disorders or other neurological problems in the immediate or extended family (e.g. familial GEFS+).

Question 41

who will have interictal positive findings on thier EEG?

Answer 41

zCertain patterns are well recognised and expected to be known (e.g. BECTS with centrotemporal spikes). Interictal EEG provides valuable information in these epileptic syndromes: BECTS, CAE, JME, LGS, and Panayiotopoulos syndrome (PS) and some focal epilepsies.

Question 42

common management issues

Answer 42

Increasing frequency of seizures and intractable epilepsy
- diagnosis
- medication
- intercurrent issue?
- notoriously difficult to control? (Certain types of epilepsy are notoriously difficult to control; examples are Lennox-Gastaut syndrome and infantile spasms.)

Question 43

non pharm strategies

Answer 43

caution with baths, diving, protective equipment qhile doing physical acitvities, safe sleeping to avoid suffocation whilst sleeping. Use monitor/alarm system, or intercom, to alert parents/carers if nocturnal seizures, if sleeping with child. avoid known precipitants.

Question 44

management considerations in adolescent females

Answer 44

take folate 5mg per day if sexually active and check wbefore starting any OTC medication

Question 45

general aims of anticonvulsant

Answer 45

monotherapy is the goal: one drug, given in the correct dosage for the child’s body weight, with drug levels checked initially (if applicable) to confirm the adequacy of the dose.

Question 46

which AEDs can have levels checked?

Answer 46

Of the ‘older’ AEDs, carbamazepine (CBZ), phenytoin (PHT) and phenobarbitone (PB) all have recommended ‘optimal’ ranges of serum drug levels, which may be useful in monitoring therapy.

Question 47

Side effects of anticonvulsants - acute toxicities

Answer 47

1. drowsiness, nystagmus and ataxia with carbamazepine and phenytoin)
2. Patients carrying HLA-B*15 : 02 are at much higher risk of developing CBZ-induced SJS/TEN
3. Patients carrying HLA-A*31 : 01 are at much higher risk of developing CBZ-induced hypersensitivity syndrome (HSS) or maculopapular exanthema (MPE); this has been described in Caucasians, Japanese, Korean and Chinese patients and patients of mixed origin

Question 48

Lamotrigine MOA

Answer 48

stabilises presynaptic membranes, inhibits excitatory neurotransmitters by blocking sodium channels, used in intractable for partial and generalised seizures.

SE: stevens-johnson; insomnia, double vision, blurred vision, dizziness, ataxia and drowsiness.

Question 49

Keppra

Answer 49

The mechanism of action is via altering intraneuronal calcium (ion) levels, by partial inhibition of N type calcium currents and by decreasing calcium ion release, from intraneuronal stores.

SE: Side effects include blurred vision, sleepiness, dizziness and poor coordination. Behavioural symptoms have been reported in up to around 40% of paediatric patients, including agitation, anxiety, apathy, depersonalisation, depression, emotional lability, hostility, hyperactivity, nervousness, neurosis and personality disorder.

Question 50

vigabatrin

Answer 50

Irreversible inhibitor of GBA transaminase; VGB increases the availability of GABA. 50% of patients have a 50% reduction in intractable partial seizures. It remains the drug of choice for West Syndrome/infantile spasms, when caused by tuberus sclerosis

SE: loss of some peripheral visual fields

Question 51

what to try in intractable epilepsy?

Answer 51

surgery;

contraindications inc Side effects include blurred vision, sleepiness, dizziness and poor coordination. Behavioural symptoms have been reported in up to around 40% of paediatric patients, including agitation, anxiety, apathy, depersonalisation, depression, emotional lability, hostility, hyperactivity, nervousness, neurosis and personality disorder.

Question 52

what workup is needed before surgery for intractable epilepsy?

Answer 52

If truly intractable, the localisation of the site of seizure initiation is detected using methods including clinical assessment, video-EEG monitoring, neuropsychology (to assess the functional importance of the site of onset: left-sided function includes verbal IQ and memory, right-sided function includes performance IQ and visual memory), CT, MRI, SPECT, PET, functional MRI and invasive monitoring. Electrical-stimulation mapping can be performed intra- or extraoperatively to identify eloquent cortex in relation to epileptogenic areas.

Question 53

what kinds of surgeries?

Answer 53

1.Seizures secondary to focal cerebral lesions: lesionectomy or partial lobectomy.

2.Seizures secondary to hemimegaloencephaly or to SWS or other large unilateral pathology: hemispherectomy.

3.Atonic seizures (drop attacks): corpus callosotomy.

Question 54

what is vagal nerve stimulation?

Answer 54

The VNS device is a battery-powered electrical pulse generator (batteries last three years) implanted under the skin in the left chest, attached to electrodes that are wrapped around the main trunk of the left vagus nerve. The device is programmed, via a computer and a handheld ‘wand’, to stimulate the vagus at various frequencies (usually for 30 seconds each 5 minutes).

Question 55

common issues for parents?

Answer 55

1.
Fear of brain damage.

2.
Being uncomfortable with the label/stigma of ‘epilepsy’.

3.
False beliefs that the cause relates to themselves (e.g. ‘stress’ during pregnancy).

4.
Equating an EEG with a treatment modality such as electroconvulsive therapy.

5.
Difficulty accepting the need for medication: ambivalence (forgetting to give medications); the belief that the need for drugs equates with, or causes, ‘intellectual disability/retardation’; and suddenly stopping the medication when the supply is used up