seizure; epileptic seizure
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Introduction
A seizure is a sudden change in behavior accompanied by motor, sensory, psychic or autonomic changes. Seizures may last seconds to minutes or persist in the case of status epilepticus. Epilepsy is the tendency towards recurrent seizures.
Classification
Etiology
- vascular
- stroke - generally embolic
- seizures may result from previously asymptomatic stroke[8]
- acute hemorrhagic stroke
- most common cause in elderly[26] (see seizures in the elderly)
- vasculitis
- AV malformations - Sturge Weber syndrome
- eclampsia
- hypertensive encephalopathy
- posterior reversible leukoencephalopathy syndrome[5]
- stroke - generally embolic
- central nervous system infections (meningoencephalitis)
- fever with seizures is Herpes
- toxoplasmosis
- cysticercosis
- syphilis
- tuberculosis
- head trauma
- loss of consciousness for at least 1 hour
- penetrating trauma causing cortical injury
- 5% without dura penetration
- 50% with dura penetration & severe head injury
- early within 1 week (usually within 24 hours)
- late - after 3 months - usually generalized, 70% chronic
- 18 months for glial scar to develop
- seizures occur on impact[5]
- brain tumor
- onset generally 35-55 years
- 10% of adult onset seizures
- astrocytoma, meningioma, CNS lymphoma (AIDS), metastatic lung cancer
- 15% of brain tumors present with seizures
- cysts
- pharmaceutical agents: (see drugs causing seizures)
- birth injury
- degenerative diseases of the CNS
- genetic disorders
- cerebral malformations
- metabolic disorders
- drug or alcohol withdrawal
- alcohol 6-36 hours after cessation
- barbiturate withdrawal
- benzodiazepine withdrawal
- toxic chemicals
- carbon monoxide poisoning
- lead poisoning
- alcohol
- illicit drugs: cocaine, amphetamines, phencyclidine[5]
- prescription drugs that lower seizure threshold
- antibiotics: cefepime, fluoroquinolones including ciprofloxacin & levofloxacin, carbapenems including imipenem, isoniazid
- piperacillin tazobactam with low risk[5]
- bupropion, clozapine, tricyclic antidepressants, tramadol
- cyclosporine, tacrolimus, theophylline[5]
- antibiotics: cefepime, fluoroquinolones including ciprofloxacin & levofloxacin, carbapenems including imipenem, isoniazid
- fever
- generally 6 months to 3 years of age
- related to rise in temperature
- increased incidence with infections with:
- syncope
- most often occurs following phlebotomy
- syncopal event precedes seizure
- eclampsia
- allergic
- idiopathic (65-70%)
- precipitants of seizures in patients with seizure disorder
- lack of sleep
- non-compliance
- infection
- pharmacologic agents
- stress
Epidemiology
- seizures most common in patients > 60 years of age
Pathology
- initiation
- hyper-excitable neurons in pathologic tissue
- normal neurons, with environmental abnormalities
- propagation - recruitment of normal neurons
- cortex to subcortex & thalamus
- tonic phase of focal seizure
- cortex to brainstem
- loss of consciousness
- generalized motor activity
- brainstem & thalamus to cortex
- generalized onset seizure
- loss of consciousness
- clonic phase occurs after development of inhibitory circuits
- cortex to subcortex & thalamus
- termination
- inhibitory circuitry
- neurotransmitter depletion
- energy source depletion
History
- timing of onset, duration, description of seizure, past seizures, compliance with medications, aura, incontinence, salivation, vomiting, aspiration, post-ictal weakness, prodrome, history of TIA, stroke or migraine, fever/chills, diabetes, family history
- eyewitness accounts of stiff limbs, twitches of all limbs, facial color, drooling, head deviation may be correct 1/2 of the time[10]
Clinical manifestations
- aura is variable (< 1 minute)[5]
- duration is 1-2 minutes[5]
- consciousness is generally compromised
- incontinence may occur[5]
- biting of the tongue, especially lateral aspect is a stronger indication of seizure than urinary incontinence[15]
- tachycardia
- confusion, amnesia. fatitue frequently occurs after seizure
- motor, sensory, psychic or autonomic changes
- most seizures occur in stage 1 sleep
- see specific seizure type
Laboratory
- complete blood count (CBC)
- comprehensive metabolic panel
- antinuclear antibody (ANA)
- urinalysis & urine toxicology screen
- therapeutic drug monitoring of anticonvulsants
- arterial blood gas (ABG)
- lumbar puncture with CSF analysis if fever, prolonged postictal state, immunosuppression or severe headache[5]
- see ARUP consult[11]
Diagnostic procedures
- electroencephalogram (EEG)
- all patients with 1st seizure
- helps differentiate partial from generalized seizures
- sleep-deprived interictal scalp EEG will show sharp waves, spikes or paroxysmal discharges in most patients with epilepsy
- a normal EEG does not rule out a seizure disorder
- especially so of seizures originating in the medial temporal lobe
- nasopharyngeal recordings or sleep studies may be helpful
- interictal eplileptiform discharges are found on 1st EEG of 25-50% of patients with seizures[5]
- normal variants, as well as electrode artifacts, may be mistaken for epileptic discharges[18]
- video EEG recording
- 1st step in assessing patients with refractory seizures for neurosurgical eligibility[5]
- 24 hour ambulatory EEG monitoring is generally not helpful
- not routinely necessary in considering medicine withdrawal[19]
- EKG: evidence of dysrhythmias
* if postictal state does not improve within 15 minutes of a seizure, obtain EEG to rule out nonconvulsive status epilepticus
Radiology
- magnetic resonance imaging (MRI) of head
- imaging modality of choice*
- indications
- all patients with unprovoked seizure
- history suggestive of partial seizure[5]
- abnormal neurologic examinination
- immunodeficiency[5]
- potentially epileptogenic MRI lesions include
- findings often discordant with EEG[12]
- computed tomography (CT) of head
- MRI not available
- hemorrhagic stroke suspected*
- cerebral angiogram
* urgent, non contrast CT to exclude intracranial hemorrhage in patients with head trauma, focal neurologic deficits, or altered mental status[5]
Complications
- hypoxia & increased muscle activity lead to lactic acidosis
- hypercarbia & respiratory acidosis
- seizure themselves may cause lesions in
- production of minor foci in contralateral hemisphere
- rhabdomyolysis, myoglobinuria & acute renal failure
- hyperpyrexia
- trauma
- aspiration
- recurrent or chronic seizures
- recurrence after a single unprovoked seizure predicted by
- traumatic brain injury[16]
- stroke[16]
- EEG with epileptiform abnormality[16]
- nocturnal seizure[16]
- abnormal neuroimaging[16]
- partial seizure
- Todd's paralysis
- family history of epilepsy
- age > 65 years
- abnormal findings on neurological exam
- recurrence highest in the 1st 2 years after 1st unprovoked seizure (21-45%)[16]
- recurrence after a single unprovoked seizure predicted by
- increase risk for psychiatric disorders in adolescence & young adulthood for seizures early in childhood[23]
- 13% for febrile seizures, 17 for epilepsy, a19% for both vs 11% for children without seizure[23]
- late-onset seizures of unknown etiology associated with risk for dementia[24]
Differential diagnosis
- syncope
- narcolepsy
- unconscious, but arousable
- no incontinence
- no tonic-clonic activity
- transient ischemic attack (TIA)
- migraine headache
- aura common 15-30 minutes
- duration hours vs 1-2 minutes for seizure
- no tonic-clonic activity
- altered consciousness is rare
- no incontinence
- rare slowing on EEG[5]
- cataplexy
- emotional trigger
- sudden loss in postural tone of the limbs
- awake, but no voluntary movement
- no incontinence
- no tonic-clonic activity
- extrapyramidal disorders
- tics* - normal, Tourette's syndrome
- dystonia - torticollis
- tardive dyskinesia - antipsychotic agents
- chorea - hereditary, infectious
- athetosis - perinatal hypoxia
- hemiballism - subthalamic nuclei injury
- tremor - Parkinson's disease, familial tremor
- myoclonus - associated with sleep
- child breath-holding spells
- hysteria
- paroxysmal vertigo
- metabolic encephalopathy
- pseudoseizure
* motor tics discovered after an episode of syncope may give the false impression of partial -> generalized seizure[18]
Management
- immediate management
- protection of airway
- correction of underlying etiology (first line)
- diazepam buccal film interictal, ictal/peri-ictal poorly controlled tonic-clonic seizures or focal seizures with impaired awareness[22]
- pharmacologic
- depends upon type of seizure & patient's ability to tolerate side effects
- indications for therapy[5][27]
- patient with single provoked seizure does not require anticonvulsant[5]
- correct underlying cause or remove offending agent: alcohol, hypoglycemia, syncope, fever
- further diagnostic testing not indicated if reversible cause identified & neurologic exam is normal[5]
- patient with single, unprovoked, generalized tonic-clonic seizure may not require therapy[5][27]
- 20-30% risk of recurrence in next 2 years if neurologic examination, EEG & MRI are normal[5]
- it is reasonable NOT to start anticonvulsant therapy because anticonvulsants only reduce risk by 50%[5]
- patient with 2 unprovoked seizures or 1 unprovoked seizure with significant brain MRI &/or electroencephalography abnormalities, risk of recurrence is > 60% & anticonvulsant treatment is recommended[5][27]
- seizures requiring pharmacologic therapy (after EEG & MRI)
- absence seizures
- partial seizures
- seizures associated with juvenile myoclonic epilepsy
- recurrent generalized tonic-clonic seizures
- seizures associated with abnormal EEG
- seizures with a focal lesion on neuroimaging
- unprovoked seizure > 1 month after stroke or head trauma[5]
- early therapy
- reduces risk of recurrence within the 1st 2 years
- has no effect on long-term seizure remission or quality of life[9][16]
- patient with single provoked seizure does not require anticonvulsant[5]
- anticonvulsive therapy
- start with single agent
- increase until seizures are controlled or adverse effects occur
- use levetiracetam in Asians until HLA-B*1502 allele testing is performed
- avoid valproic acid, carbamazepine, phenobarbital, phenytoin, topiramate in women of child-bearing age[5]
- lamotrigine & levetiracetam 1st line
- older patients taking carbamazepine at risk for hyponatremia due to SIADH[5]
- gabapentin, lamotrigine & levetiracetam 1st line
- for seizures due to brain metastases for which chemotherapy is planned, use valproic acid, lacosamide, lamotrigine or levetiracetam[5]
- risk for drug adverse effects is low ? (7-31%)[16]
- risk for drug interactions[5]
- therapeutic monitoring for anticonvulsive agents
- important for patients with:
- indadequate seizure control
- signs or symptoms of toxicity
- appropriate dose is dose that controls seizures in the absence of adverse effects, regardless of serum levels
- may be indicated with addition of new medication with potential for significant drug interaction[5]
- important for patients with:
- non-compliance is most important cause of seizures in epileptic patients
- consider withdrawing anticonvulsant therapy for patients
- without seizures for 2-5 years with normal EEG
- known precipitant of seizures without underlying brain disease
- not juvenile myoclonic epilepsy[5]
- history of difficulty in seizure control
- anticonvulsive therapy should be tapered, not abruptly discontinued
- not every patient who enters remission with medication treatment is a good candidate for medication withdrawal[19]
- relapse after stopping anticonvulsants in adults is 25-60% over 2 years[5]
- seizures during an attempt at medication withdrawal don't predict failures in future withdrawal attempts[19]
- a small fraction of patients develop refractory seizures after medication withdrawal (not known whether or not this would have occurred regardless of medication withdrawal)[19]
- 30-40% of patients do not respond to anticonvulsants[5]
- medical marijuana may improve seizure control & quality of life in refractory epilepsy[20]
- high out-of-pocket costs & inconvenient access cited as reasons for discontinuation
- see specific seizure type for specific agents
- surgery
- referral for patients not controlled by medication
- failure to control seizures despite adequate trials of 2 appropriate anticonvulsants[5]
- surgical resection of epileptic focus can provide relief or cure
- video EEG recording is the 1st step in assessing patients with refractory seizures for neurosurgical eligibility[5]
- referral for patients not controlled by medication
- vagus nerve stimulation
- treatment option for medically refractory seizures in patients not candidates for traditional surgery
- RNS stimulator FDA-approved Nov 2013 for patients without adequate response to anticonvulsants
- notification of health department
- seizure-free for 6 to 12 months before a patient with seizure disorder can legally drive (Calif); differs in different states[6]
- patient education:
- pregnancy
- risk of congenital malformations is higher in offspring of epileptic mothers
- risk increases slightly with anticonvulsive therapy [5%]
- all anticonvulsive agents implicated
- maximal fetal risk during 1st 6 weeks of gestation
- risk increases slightly with anticonvulsive therapy [5%]
- folic acid (1 mg/day) should be administered throughout pregnancy
- if pregnant, not taking anticonvulsant, no seizure in 18 months, observe[25]
- risk of congenital malformations is higher in offspring of epileptic mothers
- supplement Ca+2 & vitamin D with chronic use of anticonvulsants[5] (bone mineral density may be reduced by anticonvulsants[5][7])
- monitor lipid panel for dyslipidemia in patients on statins
- anticonvulsants may enhance clearance of statins[5]
Follow-up:
- every 3-6 months to evaluate seizure control
More general terms
More specific terms
- alcohol withdrawal seizure
- atypical seizure; psychogenenic non-epileptic spell; hysterical seizure; pseudoseizure; psychogenic seizure
- epilepsy
- faciobrachial dystonic seizure
- febrile seizure
- partial seizure; focal seizure
- primary generalized seizure
- seizures in the elderly
- Todd's paralysis
Additional terms
- International classification of epileptic seizures
- pharmaceutical agents associated with seizures; drugs that lower seizure threshold
References
- ↑ Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook, Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 829-39
- ↑ Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 1034-35
- ↑ Alan Gelb, UCSF, Department of Emergency Services, San Francisco General Hospital, 1998
- ↑ Chan & Winkle, Diagnostic History & Physical Examination, Current Clinical Strategies Publishing. Laguna Hills, 1996
- ↑ 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 5.10 5.11 5.12 5.13 5.14 5.15 5.16 5.17 5.18 5.19 5.20 5.21 5.22 5.23 5.24 5.25 5.26 5.27 5.28 5.29 5.30 5.31 5.32 5.33 5.34 5.35 5.36 5.37 5.38 5.39 5.40 5.41 5.42 Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018, 2021
Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022 - ↑ 6.0 6.1 Journal Watch 22(1):8, 2002 http://www.epilepsyfoundation.org
- ↑ 7.0 7.1 Prescriber's Letter 10(1):4 2003
- ↑ 8.0 8.1 Journal Watch 24(10):79-80, 2004 Cleary P, Shorvon S, Tallis R. Late-onset seizures as a predictor of subsequent stroke. Lancet. 2004 Apr 10;363(9416):1184-6. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15081649
- ↑ 9.0 9.1 Journal Watch 25(15):117, 2005 Marson A, Jacoby A, Johnson A, Kim L, Gamble C, Chadwick D; Medical Research Council MESS Study Group. Immediate versus deferred antiepileptic drug treatment for early epilepsy and single seizures: a randomised controlled trial. Lancet. 2005 Jun 28;365(9476):2007-13. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15950714
- ↑ 10.0 10.1 Thijs RD et al. Transient loss of consciousness through the eyes of a witness. Neurology 2008 Nov 18; 71:1713. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19015487
- ↑ 11.0 11.1 ARUP Consult: Seizure Disorders - Epilepsy deprecated reference
- ↑ 12.0 12.1 12.2 Hakami T et al. MRI-identified pathology in adults with new-onset seizures. Neurology 2013 Sep 3; 81:920 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23925763
- ↑ Kwan P, Sperling MR. Refractory seizures: try additional antiepileptic drugs (after two have failed) or go directly to early surgery evaluation? Epilepsia. 2009 Sep;50 Suppl 8:57-62. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19702735
- ↑ Krumholz A, Wiebe S, Gronseth G et al Practice Parameter: evaluating an apparent unprovoked first seizure in adults (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2007 Nov 20;69(21):1996-2007. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18025394
- ↑ 15.0 15.1 Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022 - ↑ 16.0 16.1 16.2 16.3 16.4 16.5 16.6 16.7 16.8 Young K, Fairchild DG Groups Publish New Guidelines for Treating First Seizure. Physician's First Watch, April 21, 2015 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
Neurology. April 2015 http://www.neurology.org/content/84/16/1705.full - ↑ Berg AT Risk of recurrence after a first unprovoked seizure. Epilepsia. 2008;49 Suppl 1:13-8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18184149
- ↑ 18.0 18.1 18.2 Wilner AN Diagnostic Error in Patients With Neurologic Symptoms. Medscape. Oct 31, 2016 http://www.medscape.com/features/slideshow/diagnostic-errors/neurologic
- ↑ 19.0 19.1 19.2 19.3 19.4 Lamberink HJ, Otte WM, Geerts AT et al. Individualised prediction model of seizure recurrence and long-term outcomes after withdrawal of antiepileptic drugs in seizure-free patients: A systematic review and individual participant data meta-analysis. Lancet Neurol 2017 Jul; 16:523. PMID: https://www.ncbi.nlm.nih.gov/pubmed/28483337
French JA. Withdrawal of antiepileptic drugs: An individualised approach. Lancet Neurol 2017 Jul; 16:493. PMID: https://www.ncbi.nlm.nih.gov/pubmed/28499852 - ↑ 20.0 20.1 Basen R. Epilepsy Patients Failing Regular Meds Improved with Medical Cannabis - Reported better overall health as well as seizure control in pilot study MedPage Today, Dec 05, 2017
Papalia A, et al Has the New York Medical Marijuana Program benefited medically refractory epilepsy patients? American Epilepsy Society (AES) 2017; Abstract 2.186. - ↑ Nair DR. Management of Drug-Resistant Epilepsy. Continuum (Minneap Minn). 2016 Feb;22(1 Epilepsy):157-72. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/26844735
- ↑ 22.0 22.1 George J Diazepam Film Shows Promise for Poor Seizure Control. Buccal film placed successfully during seizure clusters. MedPage Today. Dec 06, 2018
Jung C, et al. The usability of diazepam buccal soluble film as an oral treatment in adult patients with epilepsy. AmericanEpilepsy Society (AES) 2018; Abstract 3.468.
Rogawski M, et al. Pharmacokinetics of diazepam buccal soluble film in adult patients with epilepsy: comparison of bioavailability with peri-ictal and interictal administration. AmericanEpilepsy Society (AES) 2018; Abstract 2.453. - ↑ 23.0 23.1 23.2 Dreier JW, Pedersen CB, Cotsapas C, Christensen J. Childhood seizures and risk of psychiatric disorders in adolescence and early adulthood: a Danish nationwide cohort study. Lancet. Child & Adolescent Health. Dec 6, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30528754 https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(18)30351-1/fulltext
Wiznitzer M Mind the brain: the psychiatry of childhood seizures. Lancet. Child & Adolescent Health. Dec 6, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30528755 https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(18)30382-1/fulltext - ↑ 24.0 24.1 Keret O, Hoang TD, Xia F, Rosen HJ, Yaffe K. Association of Late-Onset Unprovoked Seizures of Unknown Etiology With the Risk of Developing Dementia in Older Veterans. JAMA Neurol. Published online March 9, 2020. PMID: https://www.ncbi.nlm.nih.gov/pubmed/32150220 https://jamanetwork.com/journals/jamaneurology/fullarticle/2762515
- ↑ 25.0 25.1 NEJM knowledge+ Neurology
- ↑ 26.0 26.1 Johnson EL, Krauss GL, Lee AK et al Association Between Midlife Risk Factors and Late-Onset Epilepsy. Results From the Atherosclerosis Risk in Communities Study. JAMA Neurol. Published online July 23, 2018. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30039175 https://jamanetwork.com/journals/jamaneurology/fullarticle/2688301
- ↑ 27.0 27.1 27.2 27.3 Foster E, Carney P, Liew D et al First seizure presentations in adults: beyond assessment and treatment. J Neurol Neurosurg Psychiatry. 2019 Sep;90(9):1039-1045. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30948624 Review.
- ↑ Rowland K, Lambert CE Jr. Evaluation After a First Seizure in Adults. Am Fam Physician. 2022 May 1;105(5):507-513. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35559631