REFRECTORY SEIZURES

CHAIRPERSON Dr. Ajay Gaur M.D. Ph.D Associate Professor & Head Dept of pediatrics GUIDE Dr. Sunita Prashad M.D. Asst. Professor Dept of pediatrics

Presented by: VISHAL YADAV PG Student

Seizure a seizure a difined as transient, involuntry alteration of conciusness, behaviour, motor activity, sensation or autonomic fuction coused by excessive rate & hypersynchrony of discharge from a group of cerebral neurons.

RE:

(1) Absence of response to 2 AEDs tolerated at reasonable doses.

(2) Minimum frequency of seizures (e.g.1 seizure per month) to be considered refractory or the duration of minimum remission (e.g. 6-12 months) to be qualified as non refractory. (3) Duration of 1 year to 1 decade of non controlled epilepsy.

Epilepsy- prevalence~ 5/1000

Incidence~50/100,000/year. Assuming that 20% of patients with active epilepsy would be resistant to AED treatment.

One bn population of india,

There would be about one mn people with medically

refractory epilepsy

Bodily injuries hospitalization. Shortened life spans risk of sudden unexpected death.

Significant neuropsychological, psychiatric, and social

impairments.
Limited employment, reduce marriage rates, and decrease

quality of life.

APPROACH TO A CHILD WITH REFRACTOY

Confirm true intractability. Determine the cause of intractability (a) Complete clinical evaluation (b) Appropriate investigation Devise long term treatment plan. Counsel the parents. Consider non-AED. Non-surgical treatment option Epilepsy surgery.

Type of syndrome.
Etiology.

13% of all patients with IGE, and no case with idiopathic partial epilepsy, were refractory.
78% of patients with symptomatic generalized epilepsy and 49% of patients with symptomatic partial epilepsy were not in remission.

Younger age. High sz frequency. Presentation with SE. Mixed seizure types with dev. Delay. Multiple sz types prior to treatment and after treatment

HUMAN FACTORS Wrong drug Wrong Dose Frequency Compliance ENVIRONMENTAL Trauma Drug exposure.

Exclude false refractoriness related to

Nonepileptic seizures. (20%)

Inadequate AEDs.
Noncompliance.

Seizure-precipitating factors.

Inadequate control of seizures despite at least 2 potentially

effective AEDs (mono- or polytherapy) taken in tolerable doses. Occurrence of an average of one sz per month for 18 months or more. Not more than 3 month sz free hiatus during this period of 18 months.

PROTOCOL OF PEFRACTORY SIZURES

COFIRM TRUE INTRACTABILITY

CLASSIFY TYPE OF SEIZURES AND/OR EPILEPTIC SYNDROME: DETERMINE ETIOLOGY

(IF CHILD ON POLYTHERAPY) WITHDROW ANY INAPPROPRIATE AED

INCREASE INITIAL APPROPRIATE AED TO MAX. TOLERATED DOSE No response

ADD ANOTHER AED (INCLUDING NEWER AED) AND INCREASE SIMILARLY

SEIZURES CONTROLLED

SEIZURES UNCONTROLLED

CONTINUE THE AEDs

TRY ANOTHER AED

Try to reduce dosage of other AEDs; withdraw relatively ineffective AEDs gradually

SEIZURES CONTROLLED

SEIZURES UCONTROLLED

If seizure frequency exacerbravates Reintroduce the AED that was withdrawn

CONSIDER ALTERNATIVE THERAPIES EPILEPSY SURGERY

AED FOR RE
FIRST LINE DRUGS Partial epilepsies-CBZ Generalized epilepsies VPA ADD ON DRUGS Partial-PHB, CLB;/LEV,TPM Generalized-ZNS,LEV,LTG
VPA+TPM=hyper ammonaemia
LEV+ZNS=SZ++++.

USE OF AEDs IN MANAGEMENT OF REFRACTORY PARTIAL EPILEPSY AED

Gabapentin

As adjunctive therapy in children

Gabapentin may be used as adjunctive treatment of children with refractory partial seizures (Level A).

As monotherapy
There is insufficient evidence to recommend use of gabapentin as monotherapy for refractory partial epilepsy (Level U). Lamotrigine can be used as monotherapy in patients with refractory partial epilepsy (Level B, downgraded due to dropouts).

Lamotrigine

Lamotrigine may be used as adjunctive treatment of children with refractory partial seizures (Level A).

Topiramate

Topiramate may be used as adjunctive treatment of children with refractory partial seizures (Level A).

Topiramate can be used as monotherapy in patients with refractory partial epilepsy (Level A).
There is insufficient evidence to recommend use of tiagabine as monotherapy for refractory partial epilepsy (Level U).

Tiagabine

Oxcarbazepine

Oxcarbazepine may be used as adjunctive treatment of children with refractory partial seizures (Level A).

Oxcarbazepine can be used as monotherapy in patients with refractory partial epilepsy (Level A). There is insufficient evidence to recommend use of levetiracetam as monotherapy for refractory partial epilepsy (Level U). There is insufficient evidence to recommend use of zonisamide as monotherapy for refractory partial

Levetiracetam

Zonisamide

USE OF AEDs IN REFRACTORY PRIMARY GENERALIZED EPILEPSY AND LENNOX GASTAUT SYNDROME

AED
Gabapentin

Refractory Primary Generalized Epilepsy

There is insufficient evidence to recommend gabapentin for the treatment of refractory generalized tonic-clonic seizures in adults and children (Level U).

Lennox Gastaut Syndrome

Lamotrigine

There is insufficient evidence to recommend lamotrigine for the treatment of refractory generalized tonic-clonic seizures in adults and children (Level U).
Topiramate may be used for the treatment of refractory generalized tonic-clonic seizures in adults and children (Level A). There is insufficient evidence to recommend tiagabine for the treatment of refractory generalized tonic-clonic seizures in adults and children (Level U).
There is insufficient evidence to recommend oxcarbazepine for the treatment of refractory generalized tonic-clonic seizures in adults and children (Level U). There is insufficient evidence to recommend levetiracetam for the treatment of refractory generalized tonic-clonic seizures in adults and children (Level U).

Lamotrigine may be used to treat drop attacks associated with the Lennox Gastaut syndrome in adults and children (Level A).
Topiramate may be used to treat drop attacks associated with the Lennox Gastaut syndrome in adults and children (Level A).

Topiramate

Tiagabine

Oxcarbazepine

Levetiracetam

Zonisamide

There is insufficient evidence to recommend zonisamide for the treatment of refractory generalized tonic-clonic seizures in adults and children (Level U).

ALTERNATIVE THERAPY
Non anti-epileptic drugs for refractory epilepsy NON anti epileptic drugs for refractory epilepsy 1. Adernocorticotropic hormone & steroids. ACTH as well as oral steroid are used for treatment of infantile spasm with hysarrhythmia, control infantile spam and also normalize EEG.

2. Vitamin B6 (pyridoxine ) 3. Acetazolamide

Diet restrict the quantity of carbohydrate and protein and most calories are provided as fat. Fat versus carbohydrates and protein ratio 4:1 or 3:1 Mimic like fasting. exact mechanism of action not known. Brain use fat rather than glucose in condition such as fasting or ketogenic diet, direct effect of ketones on excitability & synaptic faction of neurons and in GABA synthesis.

KETOGENIC DIET

Fatty acid oxidised in liver to ketones (B-hydroxy butyrate and acetoacetic acid and acetone).
Recommended after 1 year of age. SIDE EFFECT Renal stone, constipation, Lack of weight gain, Decrease in bone density, decrease water, acidosis.

CAUTIONS Valproate should not be used with ketogenic diet as the risk of hepatoxicity.
Acetazolamide and topirmate should avoid

VAGAL NERVE STIMULATION

In human vagal nerve stimulation (VNS) refer to stimulation of lift cervical vagus nerve its fiber cause desynchronization of electrocerebral activity & relive seizure. MECHANISM OF ACTION Exactly unknown, change in neurotransmitter. Serotonin, non-epinephrin, GABA and glutamate level increase through activation of locus cerculeus. Left vagus nerve project on both nuclei of tractus solitarius & on other medullary nuclei as well as on brain stem reticular formatio. Alteration of blood flow to specific area of forebrain and brain stem nuclei after VNS.

EPILEPTIC SURGERY
Surgery should be performed before the cousequences of epilepsy have become destructive & irreversible *& before it spread to inoperable. It should not consider unless good chance of improvement in pt quality of file (QOL) TYPE OF SURGERY:1. Anterior temporal lobectomy & amygdalohippocampectomy 2. Extra temporal resection. 3. Hemispherectomy.

4. Corpus callosotomes
5. Multiple subpial transaction.

TAKE HOME MESSAGES

Before labeling a child as having refractory epilepsy. NEE & pseudo seizure must be ensure. Appropriate trial of AEDs upto maximum tolerated dose must be given. Associate problems & comorbidity must be addressed.

Alternative non surgical therapies may be tried in some patients.

Condition when surgery can be sone & outcome is good after. surgeries particularly unilobar lesionectomies should be done. A comprehensive management program & team work is essentialness.

Thank You