Seizure overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Shakiba Hassanzadeh, MD[2]
Overview
A seizure is a transient event that is due to excessive or synchronous neuronal activity in the brain. Seizures may be provoked (by hypoglycemia or alcohol withdrawal, etc) or spontaneous (by underlying epilepsy). Signs and symptoms of seizures depend on the area of the brain that is the origin and may include loss of consciousness, confusion, visual or other sensory symptoms, body shaking, limb jerking, or a brief loss of awareness. Diagnosis of seizure is done by taking the patient's history, physical examination, EEG, and brain imaging. In the acute setting, seizures are initially treated with benzodiazepines (lorazepam or midazolam), followed by phenytoin or phenobarbital. Treatment with antiepileptic drugs (AEDs) may be required in some patients.
Historical Perspective
The term 'seizure' is derived from a Greek word meaning, 'to take hold'. Different words have been used interchangeably in historical texts, such as epilepsy, epileptic seizure, attack, or convulsion. Epilepsy has been mentioned in many documents and texts throughout history including ancient Babylonians, Egyptians, Greeks, Indian (Ayurveda), Persian (Avicenna), and Chinese. Epilepsy was first described by Hippocrates in Ancient Greece (460–377 B.C.). Until the 18th century, epilepsy was considered an idiopathic disease originating in the brain. The foundation of the modern knowledge of epilepsy was through the work of William Cullen and Samuel A. Tissot. In the 19th century, the understanding of epilepsy increased. Electroencephalography (EEG) started to gain attention in the late 19th century. In the 20th century, rapid development in medical knowledge happened (brain CT, brain MRI, and PET scan.
Classification
In 2017, the International League Against Epilepsy (ILAE) classified seizures by their onsets as focal (aware/impaired awareness, motor, nonmotor, focal to tonic-clonic seizures), generalized (motor, nonmotor), and unknown (motor, nonmotor, and unclassified). In 1981, the International League Against Epilepsy (ILAE) classified epileptic seizures as partial seizures (simple partial seizures, complex partial seizures, and partial seizures evolving to secondarily generalized seizures), generalized seizures (absence seizures, myoclonic seizures, clonic seizures, tonic seizures, tonic-clonic seizures (grand mal), and atonic seizures), and unclassified epileptic seizures.
Pathophysiology
Normally, seizures do not happen because the membrane stability of neurons is maintained, and the discharges that lead to seizures are prevented from transferring.[1]
In a normal brain, some circumstances can provoke seizures, such as:[1]
- Hyponatremia: by disrupting the electrochemical gradients across cell membranes and causing instability
- Drug withdrawal (benzodiazepines, barbiturates, and alcohol): may sensitize inhibitory GABAA receptors and stimulate a seizure
- Hypoglycemia: by changing the metabolism of cells
Abnormalities in different parts of the nervous system may cause seizure, such as brain regions, cells, ions, networks, and receptors.[1]
The imbalance of excessive excitation and reduced inhibition that causes and keeps the seizure going on.[2]
N-methyl-D-aspartate (NMDA) Receptor
- Glutamate is the most common excitation neurotransmitter and affects by the N-methyl-D-aspartate (NMDA) receptor.
- However, NMDA antagonist drugs have not been clinically successful, probably due to their effects on learning and memory.
Gamma aminobutyric acid (GABA) Receptor
- Gamma-aminobutyric acid (GABA) is the most common inhibition neurotransmitter.[2]
- GABA inhibits excess excitation of the neurons by activating the GABAA receptor.
- Increasing the inhibition of GABA (even if the inhibition is not damaged) may be helpful in a seizure, since it may overwhelm the excess excitation of the seizure.
- Examples of GABA-enhancing drugs are benzodiazepines, barbiturates, propofol, and some anesthetics.
- However, these drugs are not suitable for long term therapy since patients usually become tolerant to their effect.
- Examples of GABA-enhancing drugs are benzodiazepines, barbiturates, propofol, and some anesthetics.
Causes
Some of the causes of seizure include:[3]
- Brain injury (such as a tumor, vascular, traumatic, and developmental)
- Brain hemorrhage
- Encephalitis
- High fever
- Excessive alcohol use
- Excessive sleep deprivation
- Medications
- Metabolic abnormalities
- Withdrawal from alcohol or drugs
Differentiating Seizure from Other Diseases
Differential diagnosis of epileptic seizures may include:[4]
- Concussion
- Drug intoxication or withdrawal
- Migraine
- Psychogenic nonepileptic events
- Panic attacks
- Sleep disorders
- Syncope
- Transient global amnesia
- Transient ischemic attack (TIA)
Epidemiology and Demographics
It is estimated that 11% of the population experience a seizure in their life compared to the estimation of 3% for epilepsy. In the US, seizure is estimated to account for 1 million or 1% of emergency department (ED) visits annually. The incidence of acute symptomatic seizures is estimated to be 39 cases per 100,000 individuals in the US. Seizures are more common among males and the Black race.
Risk Factors
Risk factors that can precipitate or provoke seizure include: excessive sleep deprivation, alcohol use, illicit drug use, some medications that reduce the seizure threshold, toxins, homeostasis abnormality due to organ failure, metabolic abnormalities, and medical and surgical histories that may be important in assessing the patient’s risk for future seizures.
Screening
The EEG monitoring has been recommended in neonates with known or suspected acute brain injury combined with encephalopathy, differential diagnosis of abnormal paroxysmal events, and in high-risk populations.
Natural History, Complications, and Prognosis
The recurrence rate of seizure within two years is 35% to 40% in patients with a first-time unprovoked seizure. Status epilepticus occurs in about 6%-7% of the patients with seizure in the emergency department (ED). The overall mortality rate of status epilepticus is approximately 22% (3% in pediatric patients to 26% in adults). Simple febrile seizures are considered normal in childhood and the prognosis is generally excellent. The recurrence rate is about 12% in children that have their first febrile seizure in infancy and about 50% in those who have their first febrile seizure later.
Diagnosis
History and Symptoms
The main part of the seizure history should be about the patient’s awareness, experience, and remembrance of the seizure. Symptoms of seizure include, aura, staring spells, myoclonic jerks, impaired awareness, paresthesias, lost of consciousness, Déjà vu experiences and confusion.
Physical Examination
The physical examination of patients with seizure may reveal: lateral tongue bites, nuchal rigidity or asterixis, bruises or scrapes on the body after falls, signs of a neurocutaneous syndrome associated with epilepsy on the skin, back pain, transient or persistent focal weakness or asymmetry, and urinary incontinence.
Laboratory Findings
The laboratory tests for patients with seizure may include checking for:[5][6][6]
- Hypoglycemia
- Hyponatremia
- Uremia
- Drug intoxication
- Ammonia levels
- Creatine kinase (CK) levels
- Lactate levels
- Prolactin levels
Serum Prolactin Level: [7]
- Elevated prolactin level may be helpful in differentiating generalized tonic-clonic or complex partial seizure from psychogenic nonepileptic seizures, only if the patient’s prolactin level is measured 10 to 20 minutes after a suspected seizure event.
- Analysis of the serum prolactin level is not effective in distinguishing a seizure from syncope.
- No conclusion could be established regarding serum prolactin changes following status epilepticus, repetitive seizures, and neonatal seizures.
Electroencephalogram
EEG should be performed as soon as possible and can detect: focal sharp waves or spikes (focal epilepsy) and bilateral/generalized epileptiform activity (generalized epilepsy).[4]
CT
Computed tomography scan (CT scan) in the emergency department is helpful in ruling out hemorrhage or other lesions.[8]
MRI
- MRI scan (preferably 3 tesla) should be performed in order to detect epileptogenic lesions.[8]
- MRI is more sensitive in detecting some findings compared to CT scan.[9]
Other Imaging Findings
3-T MRI may be helpful in patients with epilepsy and negative 1.5-T MRI.[10][11]
Other Diagnostic Studies
- EEG with sleep deprivation is helpful when standard EEG does not detect any epileptiform changes.[12]
- Lumbar puncture (LP) should be considered in those patients suggesting the following causes:[5]
Treatment
Medical Therapy
- In the acute setting, seizures are initially treated with benzodiazepines (lorazepam or midazolam), followed by phenytoin or phenobarbital.[13]
- Antiepileptic drugs (AEDs) are commonly used in treating focal and generalized epilepsies.[4]
Surgery
- Surgery may be helpful in patients with focal epilepsy if there is no seizure control after two or more antiepileptic drugs (AEDs).
- Laser interstitial thermal ablation and neurostimulation may be helpful as alternative therapies to surgery in some patients.[4]
Primary Prevention
- Some of the preventable etiologies for epilepsy that should be considered in primary prevention include central nervous system (CNS) infection, CNS parasitosis, pre- and perinatal brain insults, stroke, and traumatic brain injury (TBI).[14]
- Some factors that can perticipate or provoke seizure may include excessive sleep deprivation, alcohol use, illicit drug use, some medications that reduce the seizure threshold, toxins, homeostasis abnormality due to organ failure, metabolic abnormalities, and medical and surgical histories that may be important in assessing the patient’s risk for future seizures.[15][16][5]
Secondary Prevention
- Patients that have has first seizures should be counseled for their seizure and the possible etiology, lifestyle considerations (safety measures and avoidance of the factors that can lower the seizure threshold and predispose to recurrences, such as sleep deprivation, use of alcohol, and illicit drugs), driving, antiepileptic drugs (AED) and their side effects, and follow-up.[3]
- Patients, family members, friends, and co-workers should be counseled for seizure first aid during a seizure event such as removal of harmful objects, repositioning the patient in order to support breathing, timing the seizure, calling for help, not restraining or holding the patient down, and not putting anything in the patient's mouth.[3]
Cost-Effectiveness of Therapy
The national economical impact of epilepsy is estimated at $9.6 billion per year in the United States.[17]
Future or Investigational Therapies
Further studies are required for producing new drugs with novel mechanisms of action and finding new treatments by increasing the knowledge of the mechanisms of dietary therapy in epilepsy and the role that neurosteroid hormones have in exacerbating epilepsy.[4]
References
- ↑ 1.0 1.1 1.2 Huff JS, Fountain NB (2011). "Pathophysiology and definitions of seizures and status epilepticus". Emerg Med Clin North Am. 29 (1): 1–13. doi:10.1016/j.emc.2010.08.001. PMID 21109098.
- ↑ 2.0 2.1 Fountain NB, Lothman EW (1995). "Pathophysiology of status epilepticus". J Clin Neurophysiol. 12 (4): 326–42. PMID 7560021.
- ↑ 3.0 3.1 3.2 Legg KT, Newton M (2017). "Counselling adults who experience a first seizure". Seizure. 49: 64–68. doi:10.1016/j.seizure.2016.09.012. PMID 27720347.
- ↑ 4.0 4.1 4.2 4.3 4.4 Johnson EL (2019). "Seizures and Epilepsy". Med Clin North Am. 103 (2): 309–324. doi:10.1016/j.mcna.2018.10.002. PMID 30704683.
- ↑ 5.0 5.1 5.2 Gavvala JR, Schuele SU (2016). "New-Onset Seizure in Adults and Adolescents: A Review". JAMA. 316 (24): 2657–2668. doi:10.1001/jama.2016.18625. PMID 28027373.
- ↑ 6.0 6.1 Nass RD, Sassen R, Elger CE, Surges R (2017). "The role of postictal laboratory blood analyses in the diagnosis and prognosis of seizures". Seizure. 47: 51–65. doi:10.1016/j.seizure.2017.02.013. PMID 28288363.
- ↑ Chen DK, So YT, Fisher RS, Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology (2005). "Use of serum prolactin in diagnosing epileptic seizures: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology". Neurology. 65 (5): 668–75. doi:10.1212/01.wnl.0000178391.96957.d0. PMID 16157897.
- ↑ 8.0 8.1 Bank AM, Bazil CW (2019). "Emergency Management of Epilepsy and Seizures". Semin Neurol. 39 (1): 73–81. doi:10.1055/s-0038-1677008. PMID 30743294.
- ↑ Radue EW, Scollo-Lavizzari G (1994). "Computed tomography and magnetic resonance imaging in epileptic seizures". Eur Neurol. 34 Suppl 1: 55–7. doi:10.1159/000119510. PMID 8001611.
- ↑ Ladino LD, Balaguera P, Rascovsky S, Delgado J, Llano J, Hernández-Ronquillo L; et al. (2016). "Clinical Benefit of 3 Tesla Magnetic Resonance Imaging Rescanning in Patients With Focal Epilepsy and Negative 1.5 Tesla Magnetic Resonance Imaging". Rev Invest Clin. 68 (3): 112–8. PMID 27408997.
- ↑ Knake S, Triantafyllou C, Wald LL, Wiggins G, Kirk GP, Larsson PG; et al. (2005). "3T phased array MRI improves the presurgical evaluation in focal epilepsies: a prospective study". Neurology. 65 (7): 1026–31. doi:10.1212/01.wnl.0000179355.04481.3c. PMID 16217054.
- ↑ Schreiner A, Pohlmann-Eden B (2003). "Value of the early electroencephalogram after a first unprovoked seizure". Clin Electroencephalogr. 34 (3): 140–4. doi:10.1177/155005940303400307. PMID 14521275.
- ↑ Glauser T, Shinnar S, Gloss D, Alldredge B, Arya R, Bainbridge J; et al. (2016). "Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society". Epilepsy Curr. 16 (1): 48–61. doi:10.5698/1535-7597-16.1.48. PMC 4749120. PMID 26900382.
- ↑ Thurman DJ, Begley CE, Carpio A, Helmers S, Hesdorffer DC, Mu J; et al. (2018). "The primary prevention of epilepsy: A report of the Prevention Task Force of the International League Against Epilepsy". Epilepsia. 59 (5): 905–914. doi:10.1111/epi.14068. PMC 7004820 Check
|pmc=value (help). PMID 29637551. - ↑ Pohlmann-Eden, Bernd; Legg, Karen T. (2013). "Treatment of first seizure in adults: A comprehensive approach integrating 10 key principles". Epileptology. Elsevier BV. 1 (1): 61–67. doi:10.1016/j.epilep.2013.01.005. ISSN 2212-8220.
- ↑ Delanty N, Vaughan CJ, French JA (1998). "Medical causes of seizures". Lancet. 352 (9125): 383–90. doi:10.1016/S0140-6736(98)02158-8. PMID 9717943.
- ↑ Yoon D, Frick KD, Carr DA, Austin JK (2009). "Economic impact of epilepsy in the United States". Epilepsia. 50 (10): 2186–91. doi:10.1111/j.1528-1167.2009.02159.x. PMID 19508694.