OU Neurology

Seizures and Epilepsy:A practical guide to primary care providers

Bhrugav Raval, M.D.

Assistant Professor

Department of Neurology

The University of Oklahoma Health Sciences Center

OU Neurology

RELEVANT DISCLOSURE & RESOLUTION

I have no relevant financial relationships or affiliations with commercial interests to disclose.

OU Neurology

LEARNING OBJECTIVES

◼Describe basics of seizures and epilepsy including different types, symptoms, understand underlying etiologies and common alternative diagnoses that mimic seizures

◼Describe different treatment options, including medications and neurostimulation devices depending on the seizure type

◼Describe role of tertiary level epilepsy center in management of complicated epilepsy patients

OU Neurology

Seizure

◼ International League Against Epilepsy (ILAE) defines an epileptic seizure as “a transient occurrence of signs and/orsymptoms due to abnormal excessive or synchronous neuronalactivity in the brain”

OU Neurology

Epilepsy

◼“Epilepsy is a disorder of the brain characterized by an enduringpredisposition to generate epileptic seizures and by theneurobiologic, cognitive, psychological, and socialconsequences of this condition.”

◼The definition of epilepsyrequires the occurrence of at least one epileptic seizure.

OU Neurology

Epilepsy - Epidemiology

◼Affects 50 million people worldwide

➢80% of these live in low to middle-income countries

◼ In United States,

➢Prevalence ~ 1%; 3 million cases in US

➢150,000 new cases every year

➢1 in 26 people in US will develop epilepsy at some point in their life

OU Neurology

OU Neurology

Approach to first seizure

◼Step 1: Ascertain diagnosis of seizure vs non epileptic spells

◼Step 2: Determine whether seizure is

➢Acute symptomatic

➢Provoked

➢Unprovoked (risk of epilepsy)

◼Step 3: Workup to evaluate for etiology/confirm diagnosis

◼Step 4: Treatment

OU Neurology

Taking history

◼ Spell description: Provided by patient as well as witness accounts

➢Presence of premonitory symptoms or “aura”

➢ Features suggestive of epileptic seizure

▪ Lip smacking, unresponsiveness (temporal lobe seizures)

▪ Presence of tonic-clonic activity

▪ Presence of tongue bite or bowel/bladder incontinence

▪ Presence of post-ictal confusion/speech problems/motor weakness

➢ Feature typically not associated with epileptic seizure

▪ Premonitory symptoms of lightheadedness, “faint” sensation

▪ Quick return to baseline

OU Neurology

Taking history

◼Past history

➢Assessment of risk factors for epilepsy include history of CNS infections, history of major head trauma (penetrating), history of febrile seizures as well as family history of seizure or similar spells.

OU Neurology

Physical examination

◼General examination

➢Evidence of physical injuries – e.g.. shoulder dislocation or vertebral fractures can occur with convulsive seizures

➢Presence of fever

◼Neurological examination

➢Presence of focal deficits

➢Persistent altered mental status

OU Neurology

Acute symptomatic seizure

• Secondary to acute neurological injury

• E.g. penetrating head trauma with intracerebral hemorrhage, herpes encephalitis

Provoked seizure

• Similar to acute symptomatic seizure

• Typically secondary to transient and reversible etiology –e.g. drug ingestion, toxins, metabolic derangements

Unprovoked seizure

• No definite trigger noted

• Higher chances of recurrence

OU Neurology

Acute symptomatic seizure/Provoked seizure

◼ Etiologies

➢Acute cerebrovascular events –Ischemic stroke, subarachnoid hemorrhage, intraparenchymal hemorrhage, cerebral venous sinus thrombosis

➢Traumatic brain injury

➢CNS Infections – Herpes Encephalitis, neurocysticercosis

➢Metabolic derangements▪ Hyponatremia, Hypo/Hyperglycemia,

Hypomagnesaemia, Hypocalcemia

➢High Fever “Febrile seizures”

◼ Etiologies

➢Medications – e.g. certain anti-depressants, anti-psychotics, anti-neoplastic agents, Benzodiazepine/Barbiturate withdrawal

➢Alcohol – intoxication and withdrawal

➢ Illicit drugs – cocaine, amphetamine-like, LSD, etc.

➢Eclampsia

➢Anoxic encephalopathy

OU Neurology

Why does it matter?

• Compared mortality and risk of subsequent

unprovoked seizures in 2 groups – one with acute

symptomatic seizures and other with unprovoked

seizure

• Results

• Patients with acute symptomatic

seizure

• Are 9 times more likely to die

in 1st 30 days compared to

patients with unprovoked

seizure

• had 80% less chance to

develop subsequent

unprovoked seizure compared

to patients with first

unprovoked seizure.

• Summary – “Acute symptomatic

seizures have a higher early

mortality and a lower risk for

subsequent unprovoked

seizure.”

OU Neurology

Evaluation of Unprovoked Seizures

◼OBJECTIVES

➢Classification of seizure type based on semiology (description)

➢Workup for possible underlying etiology

➢Assessment for risk of further seizures

OU Neurology

MotorTonic-clonic

Other motor

Non-Motor (Absence)

Unknown Onset

Motor

Non-Motor

focal to bilateral tonic-clonic

Generalized OnsetFocal Onset

Motor

Tonic-clonic

Other motor

Non-Motor

ILAE 2017 Classification of Seizure Types Basic Version 1

Unclassified 2

1 Definitions, other seizure types and descriptors are listed in the accompanying paper & glossary of terms

2 Due to inadequate information or inability to place in other categories

Aware Impaired

Awareness

From Fisher et al. Instruction manual for the ILAE 2017

operational classification of seizure types. Epilepsia doi:

10.1111/epi.13671

OU Neurology

OU Neurologyhttps://ewct.org.nz/epilepsy-types/

St Louis EK, Cascino GD. Diagnosis of Epilepsy and Related Episodic

Disorders. Continuum (Minneap Minn). 2016 Feb;22(1 Epilepsy):15-37.

OU Neurology

Epilepsy Type

Scheffer IE et al. Epilepsia. 2017 Apr;58(4):512-521.

OU Neurology

Etiology of Epilepsy

◼ Structural

➢ Stroke

➢ Tumors

➢ Cortical malformations

▪ Focal cortical dysplasia

▪ Pachygyria

▪ Polymircrogyria

➢ Traumatic brain injury

◼ Infectious

➢ Meningitis

➢ Encephalitis – e.g. HSV

◼ Metabolic

➢ Glycogen storage disorders

◼ Inflammatory

➢ Autoimmune epilepsies

▪ e.g. Leucine-rich Glioma Inactivated I

▪ NMDA receptor antibodies

▪ Voltage-gated Potassium Channel complex antibodies

◼ Genetic

➢ Dravet syndrome, autosomal dominant nocturnal frontal lobe epilepsy, genetic generalized epilepsies, etc..

OU Neurology

Epilepsy Syndromes

OU Neurology

OU Neurology

Role of Neuroimaging: MRI Brain

Traumatic Brain

Injury – Multiple

regions of

encephalomalacia

OU Neurology

A/B – Left frontal cortical dysplasiaWhite arrow – periventricular nodular heterotopia

Black arrow – cortical dysplasia

OU Neurology

Right temporal cavernous hemangioma

OU Neurology

MRI Brain without contrast showing left mesial temporal sclerosis in patient with medically refractory

seizures characterized by burning sensation in stomach rising into chest, with hand automatisms and loss

of awareness.

OU Neurology

Right temporal dysembyroplastic neuroepithelial tumor (DNET)

OU Neurology

Role of Electroencephalogram (EEG)

◼Most commonly performed and one of the most important tool in diagnosis of epilepsy

◼Can help confirm the diagnosis of epilepsy, give information about localization of seizures and can help guide treatment including possibility of withdrawal of medication.

OU Neurology

EEG in epilepsy

◼ Epileptiform discharge

➢ Spike, sharp wave, spike and wave discharge

➢ Suggest increased tendency to have seizures

➢Normal EEG does not rule out epilepsy

◼ Factors affecting diagnostic yield

➢Age of patient

➢Type of epilepsy syndrome

➢Proximity of EEG to seizure

➢AED therapy

OU Neurology

Video-EEG study

◼ Indications

➢ Evaluation of spells

➢ Seizure classification

➢ Seizure quantification

➢Assessment of seizure precipitatingfactors, ands

➢ Surgical localization in drug-resistant focal epilepsy.

OU Neurology

OU Neurology

Non-epileptic episodic spells

Non-epileptic spells

Physiologic

NeurologicNon-

neurologic

Psychogenic

OU Neurology

◼ Neurological

➢Cerebrovascular events▪ Transient ischemic attacks

➢Migraine

➢Movement disorders▪ Paroxysmal dyskinesia

▪ Dystonia

▪ Tremor

◼ Non-neurological

➢ Syncope▪ Vasovagal

▪ Cardiogenic

▪ Hypotensive

➢ Sleep disorders▪ Non-REM sleep disorders, e.g..

confusional arousal

▪ REM sleep disorder

OU Neurology

OU Neurology

Psychogenic nonepileptic seizures

◼One of the most common imitators of refractory epilepsy

◼Estimated 25-30% of patients with refractory epilepsy often have psychogenic non-epileptic seizures (PNES)

◼Risk factors

➢History of physical/emotional/sexual trauma or abuse

➢Presence of psychiatric co-morbidities, most commonly depression

OU Neurology

OU Neurology

PNES

◼ Diagnosis

➢Video-EEG testing is gold-standard for diagnosing PNES

➢Ambulatory/home EEG may be useful but in-hospital EEG often preferred

◼ Treatment

➢Targeted cognitive-behavioral-therapy is the treatment of choice

➢Goal to remove predisposing, precipitating and perpetuating factors

➢Treatment of co-morbidities

OU Neurology

Epilepsy: Approach to treatment

1. Evaluation of seizure type – provoked/symptomatic vs unprovoked

2. Evaluation of possible etiology and defining epilepsy syndrome, if any

3. Evaluation of risk of seizure recurrence

OU Neurology

OU Neurology

Choosing antiepileptic drug

◼Rules to follow

1. Choosing most-effective medication for type of seizure

2. Considering side-effect profile of AEDs and patient characteristics

3. Considering convenience of administration

4. Considering cost

OU Neurology

Introduction of anti-seizure drugs (ASDs) to the market from 1853 to 2019.

Wolfgang Löscher et al. Pharmacol Rev 2020;72:606-638

OU Neurology

OU Neurology

AED use in specific situations

OU Neurology

AED: General considerations

◼ Risk of allergic reaction is present with all anti-seizure medication; highest for lamotrigine, carbamazepine

◼ Risk of suicidal ideations and mood changes is present with all anti-seizure medications

◼ Dose titration is often required for most anti-seizure medications

◼ Use FDA prescribing information for all medications as a guide for initial and maintenance dose

◼ Study blackbox warnings and common precautions for any agent being tried

OU Neurology

Epilepsy comorbidities

◼Psychiatric disorders

➢Depression: 23%

➢Anxiety: 20%

➢Suicide: 3 times higher risk

➢Attention deficit

◼Memory impairment

OU Neurology

Sudden Unexpected Death in Epilepsy Patients (SUDEP)

◼ The SUDEP is a sudden, unexpected, nontraumatic, nondrowning death in a person with epilepsy

◼ Incidence of SUDEP is 1:4500 children with epilepsy in 1 year and 1:1000 adults with epilepsy in 1 year.

OU Neurology

Driving and epilepsy

◼ Inability to drive is one of the most disabling factor in epilepsy

◼ In United States, each state has its own rules and regulation

➢Primarily determined by duration of seizure freedom, ranging from 3 to 12 months among states

➢Some states requires mandatory reporting of patients with seizures

◼ In Oklahoma

➢6-month seizure freedom required (some exceptions)

OU Neurology

Medically Refractory Epilepsy

◼ ILAE defined medically intractable epilepsy, as “a failure of adequate trials of two tolerated, appropriately chosen and used anticonvulsant drug schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom.”

◼ Refractory epilepsy

➢ Increased risk for premature death, injuries, psychosocial problems and death

➢ Increased economic burden – total national cost for acute care of patients with epilepsy in 2008 was $2.7 billion.

@ Continuum Feb 2016

OU NeurologyTang et al. Front Neurol July 2017.

OU Neurology

Refractory epilepsy can be identified early !!

• 525 patients with epilepsy

• 63% of patients remained seizure

free during anticonvulsant

treatment or after treatment was

stopped.

• Seizure-free rates were similar

between established drug (67%)

and a new drug (69%).

• Among the 470 patients

previously untreated, 47%

became seizure free during

treatment with the first drug and

14% became seizure free after

treatment with the second or third

drug.

Kwan P, Brodie MJ, NEJM Feb 2000.

OU Neurology

Therapeutic Options for Refractory Epilepsy

Antiepileptic agents

Resective surgery

Dietary therapies

Experimental drug/device

trials

Neuro-

stimulation

OU Neurology

Figure 1

Mayo Clinic Proceedings 2017 92, 1427-1444DOI: (10.1016/j.mayocp.2017.05.005)

OU Neurology

OU Neurology

Labiner DM et al.National Association of Epilepsy Centers. Essential

services, personnel, and facilities in specialized epilepsy centers--

revised 2010 guidelines. Epilepsia. 2010 Nov;51(11):2322-33.

OU Neurology

THANK YOU

OU Neurology

References

1. St Louis EK, Cascino GD. Diagnosis of Epilepsy and Related Episodic Disorders. Continuum (Minneap Minn). 2016 Feb;22(1 Epilepsy):15-37. doi: 10.1212/CON.0000000000000284. PMID: 26844728.

2. Pack AM. Epilepsy Overview and Revised Classification of Seizures and Epilepsies. Continuum (Minneap Minn). 2019 Apr;25(2):306-321. doi: 10.1212/CON.0000000000000707. PMID: 30921011.

3. Hesdorffer DC, Benn EK, Cascino GD, Hauser WA. Is a first acute symptomatic seizure epilepsy? Mortality and risk for recurrent seizure. Epilepsia. 2009 May;50(5):1102-8. doi: 10.1111/j.1528-1167.2008.01945.x. Epub 2009 Jan 26. PMID: 19374657.

4. Schuele SU. Evaluation of Seizure Etiology From Routine Testing to Genetic Evaluation. Continuum (Minneap Minn). 2019 Apr;25(2):322-342. doi: 10.1212/CON.0000000000000723. PMID: 30921012.

5. Bergey GK. Management of a First Seizure. Continuum (Minneap Minn). 2016 Feb;22(1 Epilepsy):38-50. doi: 10.1212/CON.0000000000000271. PMID: 26844729.

6. Fountain NB. Choosing among antiepileptic drugs. Continuum (Minneap Minn). 2010 Jun;16(3 Epilepsy):121-35. doi: 10.1212/01.CON.0000368235.64857.cf. PMID: 22810318.

7. Chen H, Koubeissi MZ. Electroencephalography in Epilepsy Evaluation. Continuum (Minneap Minn). 2019 Apr;25(2):431-453. doi: 10.1212/CON.0000000000000705. PMID: 30921017.

8. Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000 Feb 3;342(5):314-9. doi: 10.1056/NEJM200002033420503. PMID: 10660394.

9. Tang F, Hartz AMS, Bauer B. Drug-Resistant Epilepsy: Multiple Hypotheses, Few Answers. Front Neurol. 2017 Jul 6;8:301. doi: 10.3389/fneur.2017.00301. PMID: 28729850; PMCID: PMC5498483.

10. Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, Hirsch E, Jain S, Mathern GW, Moshé SL, Nordli DR, Perucca E, Tomson T, Wiebe S, Zhang YH, Zuberi SM. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017 Apr;58(4):512-521. doi: 10.1111/epi.13709. Epub 2017 Mar 8. PMID: 28276062; PMCID: PMC5386840.

OU Neurology

References

11. Löscher W, Potschka H, Sisodiya SM, Vezzani A. Drug Resistance in Epilepsy: Clinical Impact, Potential Mechanisms, and New InnovativeTreatment Options. Pharmacol Rev. 2020 Jul;72(3):606-638. doi: 10.1124/pr.120.019539. PMID: 32540959; PMCID: PMC7300324.

12. Yoo JY, Panov F. Identification and Treatment of Drug-Resistant Epilepsy. Continuum (Minneap Minn). 2019 Apr;25(2):362-380. doi:10.1212/CON.0000000000000710. PMID: 30921014.

13. Labiner DM, Bagic AI, Herman ST, Fountain NB, Walczak TS, Gumnit RJ; National Association of Epilepsy Centers. Essential services, personnel, and facilities in specialized epilepsy centers--revised 2010 guidelines. Epilepsia. 2010 Nov;51(11):2322-33. doi: 10.1111/j.1528-1167.2010.02648.x. PMID: 20561026.

14. Edwards CA, Kouzani A, Lee KH, Ross EK. Neurostimulation Devices for the Treatment of Neurologic Disorders. Mayo Clin Proc. 2017Sep;92(9):1427-1444. doi: 10.1016/j.mayocp.2017.05.005. PMID: 28870357.

15. Fisher RS, Cross JH, D'Souza C, French JA, Haut SR, Higurashi N, Hirsch E, Jansen FE, Lagae L, Moshé SL, Peltola J, Roulet Perez E, Scheffer IE, Schulze-Bonhage A, Somerville E, Sperling M, Yacubian EM, Zuberi SM. Instruction manual for the ILAE 2017 operational classification of seizure

16. Noe K. Counseling and Management of the Risks of Living With Epilepsy. Continuum (Minneap Minn). 2019 Apr;25(2):477-491. doi: 10.1212/CON.0000000000000708. PMID: 30921019.

OU Neurology

Questions

◼Email: Bhrugav-Raval@ouhsc.edu