Intractabel Seizures

7/28/2019 Intractabel Seizures

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INTRACTABLE SEIZURESDIAGNOSIS AND SYMPTOMSBagian Ilmu Penyakit SarafRS BayukartaKarawang


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INTRODUCTION

About 20% of the people who haveepilepsy have seizures that areresistant to anticonvulsant medication

Another 20% have seizures which areonly partially responsive to drugs

These drug-resistant are calledintractable, and the patients who

have them a mayor challenge tophysicians, neurologists and epilepsyassociations


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Definition Diagnosis of Intractable epilepsy

Intractable is defined : not to be guided, notmanageable or docile, uncontrollable, refractory,stubborn

A population of epileptic neurons must exist

within the CNS. These neurons are subject toparoxysmal depolarization shifthyperexcitable

Hyperexcitable neurons may be limited to aspecific area of the CNS localization relatedepilepsy

A widely distribution involving neuronalnetworks with diminished inhibition or excessiveexcitation generalized epilepsies


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Definition Diagnosis ofIntractable epilepsy

Antiepileptic medications (AEMs) do not alterthe epileptic neurons permanently, rather theymodulate neuronal excitability by many actions :

- influencing the chloride channel (VPA,BNZD, BARB)

- limiting the spread of repetitive dicharges

by affecting the sodium channel (PHT, CBZ)

These effects are present only when sufficientconcentrations of AEMs occur at the specificreceptor sites


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Definition Diagnosis of Intractableepilepsy

Intractable epilepsy : as seizureswhich have not been completelycontrolled with AEMs one year afteronset, despite accurate diagnosis and

carefully monitored treatment. Once intractable, there is a low

probability of remission Predictors of intractability include the

presence of partial seizures, structuralabnormalities on imaging studies, andabnormalities on the neurologicalexamination.


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Evaluation of a person with IntractableEpilepsy

1. Seizures must be correctly diagnosed1.1 Correctly identify seizure type1.2 Rule out non-epileptic events

2.1 Physiologic, i.e. Cardiac2.2 Psychogenic

2. Treatment must be monitored2.1 For therapeutic concentrations2.2 For compliance

2.1 Serial blood levels2.2 Asking about compliance


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Presence of the following Is OftenAssociated with Intractability

Seizure type : Complex partial seizures

Multiple seizure types

Frequent tonic-clonic seizures

Status epilepticus

Age of Onset : Onset in childhood (i.e. Lennox-

Gestaut Syndrome)

Onset in adulthood

EEG findings : Slow backgroundInterictal activity


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Presence of the following Is OftenAssociated with Intractability

Etiology : Symptomatic epilepsy

Clinical findings :

- Abnormal neurological examination

- Abnormal neuropsychological testing

Treatment : Delay from time ofdiagnosis to treatment


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COMPLEX PARTIAL SEIZURES(CPS)

Cardinal symptoms of CPS :

There is impairment of interaction with the

environment during the seizures Behavior during the seizure is often a

motionless stare with automatisms

Seizure is often preceded by a simple partial

seizure (aura) : may be an epigastric sensation, an affective symptom such as fear or anexperiential phenomenon such as an out ofbody experience


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COMPLEX PARTIAL SEIZURES(CPS)

The Diagnosis of CPS based on : seizuredescription, neurological examination,neurological history, interictal and ictal EEG

and MRI scanning. CPS are the most common seizures in adult,

and some of the most drug resistant. Onsetcan occur at any time of life

They may arise from the frontal, parietal ormost commonly temporal lobes and involvethe limbic structures


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Why are Complex Partial Seizures inIntractable?

The Kindling Model :

Low intensity current to trigger focal seizureactivity (often amygdala, hippocampus) with

repetition to propagate into more and moreextra focal sites, until eventually secondarilygeneralized motor seizures occur

Kainic acid (KA) injection:

Local (intrahippocampal) or systemicinjection of KA can induce seizures and leadto chronic epileptic behaviour


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Mean Afterdiscarrge Thershold (uA) in long-Evans Rats

Initial Threshold % Drop after

(mean) 40-60 stimulations

AMYGDALA 111.0-158.3 59.0%11

HIPPOCAMPUS

Dorsal (region not specified) 91.7-179.0 25.0%11

Dorsal fascia dentata 62.0 ___13

Dorasal CA1 40.6 ___13

Ventral fascia dentata 109.0 ___13Ventral CA1 76.0 ___13

SEPTAL AREA 328.0-340.0 ___13

PYRIFORM CORTEX 128.0-130.4 43.1%12

CINGULATE CORTEX 176.6-193.8 39.0%12

NEOCORTEX

Area 2 293.8-325.0 27.9% 12Area 6 265.0-328.1 31.4% 12

Area 17 306.0-326.0 15.0% 12

Area 18a 331.2-343.8 19.3% 12

MRF (10 second)

Forelimb Clonus 772 ___6

Forelimb Tonic Extension 940.0-1034.0 ___6


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WESTS SYNDROME (INFANTILE SPASMS)

West syndrome (WS) a serious epilepticsyndrome

Usually begins in the first year of life

It involves seizures as infantile spasms(IS) :brief contraction muscles of neck, trunk, andextremities, usually bilaterally simmetrically

William West (1841) : flexi spasms, jackknife

seizures, massive spasms and infantilemyoclonic seizures, associated with MR

Gibbs and Gibbs (1952) : interictal EEG patternhiparrhythmia


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Triad of infantile spasms ( myoclonicspasms), hyparrhythmia EEG and MRhas become known Wests syndrome

WS is considered one of the mostrefractory epilepsies of childhood (nearlyhalf the patients are left with intractableepilepsy and mental retardation)

Wests syndrome resists most of thestandard anticonvulsant. It may respondto steroid or some of the newer drugs


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40% of cases, no associated etiologicalfactors can be identified, 60% a wide varietyof neurological conditions :metabolic,dysplastic or dysgenetic

abnormalities, and various prenatal,perinatal, and postnatal insult Symptomatic, cryptogenic, idiopatic subgroup Diagnosed require neurological and physical

examination , development assessment, and

laboratory Neuroimaging : reveal abnormalities 60-90%

of cases, most commonly diffuse atropy


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PATHOPHYSIOLGY OF INFANTILE SPASMS

NEUROTRANSMITTERS AND BASICMECHANISMS

Increased activity of serotonergic and /oradrenergic systems or decreased activityof cholinergic systems of the brain stem

Disturbances of the GABA system (level ofGABA low in CSF)

Low CSF concentration of ACTH in infantilespasms

Increased corticotropin-releasinghormone synthesis


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PATHOPHYSIOLGY OF INFANTILE SPASMS

NEUROTRANSMITTERS AND BASIC MECHANISMS Lower levels of gangliotetraose-series

gangliosides in CSF of patients with infantilespasms

Serologic HLA typing studies: increasedrepresentation of DRw52immunological mechanisms

Other studies on the genetic predisposition toinfantile spasms


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LENNOX-GASTAUT SYNDROME(LGS)

LGS is widely known as one of the most severeand prognostic unfavorable epileptic condition

Its entity as a syndrome :

- occurrence of certain characteristic types

of seizure (particularly drop attacks and

axial tonic seizures)- EEG pattern slow spike-wave complex and

runs of rapid spikes (10-25/sec)


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CLINICAL SYMPTOMATOLOGY AND CONSIDERATIONS

Age of onset ; most commonly ages 1 - 10 years

Prevalence : 5.1%

No special gender predominance

More often in white rather than black population

Etiologies ; idiopathic and symptomatic

LGS may follow a preceding Wests syndrome

Often beginning with mayor convulsion (GTC)before the typical ictal semeiologi of LGS manifestsitself


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In symptomatic cases, all forms of CP mayassociated with LGS.

Neurological deficits, hydrocephalic,andmicrocephalic skull

Some degree of mental retardation

Serious behavioral changes are uncommon

In late onset psychotic degree my occur CT scan, MRI are essential for structural

impairment


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THE LANDAU-KLEFFNER SYNDROME

LANDAU and KLEFFNER,1957: an idiopathicsyndrome

- acquired aphasia

- seizures ( focal motor, tonic-clonicatypical absence and atonic)

- paroxysmal EEG abnormalities

(especially ESES during sleep)

Anticonvulsant, or the passage of time , mycontrol the seizures , but speech recovery isvariable, and aphasia my persist


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THE LANDAU-KLEFFNER SYNDROME

Clinical characteristic :

- the first sign occur between 3-8 years

- language dysfunction (more than 50% of

cases)- clinical seizures(40-50%)

- aphasia before age 6 years 70%, after 8

years < 10%

- affected males outnumber female 2 : 1


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CONCLUSIONS

Intractable epilepsy defined as seizures which havenot been completely controlled with AEMs one yearafter onset, despite accurate diagnosis and carefullymonitored treatment

Once intractable, there is a low probability ofremission

Predictors of intractability include the presence ofpartial seizures, structural abnormalities on imaging ,and abnormalities on neurological examination

Several kinds of intractable epilepsy : complex partialseizures, Wests syndrome (Infantile spasms),Lennox- Gestaut Syndrome, and Landau-KleffnerSyndrome


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Intractabel Seizures