Status Epilepticus: Classification, Clinical Features, and Diagnosis

Rizwan Raheem (1), Filzah Faheem (2), Junaid Kalia, MD (3)
1 - King Edward Medical University , Pakistan
2 - Services Institute of Medical Sciences, Pakistan
3 - Founder AINeuroCare.com, Texas, USA


Introduction

  • A medical and neurological emergency condition
The International League Against Epilepsy (ILAE) defines as
A single epileptic seizure for >30 min duration
OR
A series of epileptic seizures without regaining function for> >30 min period
  • Operational definition in adults and children >5 years old
    • ≥5 minutes of continuous seizures, or
    • ≥2 discrete seizures between which there is incomplete recovery of consciousness
  • Operational dimensions
    • Time point t1
      • time during which the treatment should be started
    • Time point t2
      • time during which long-term complications can occur.
  • Condition results from
    • failure of the seizure termination mechanisms
    • initiation of mechanisms leading to seizure (after time point t1)
  • Long-term consequences include
    • neuronal death
    • neuronal injury
    • neuronal networks alteration
      • Consequences depend upon
        • type of seizure
        • duration of seizures
        • occur after time point t2
  • Rapid management
    • reduces morbidity
    • Decreases mortality
  • Delayed management results in
    • poor prognosis
    • poor refractory seizure control
 

Epidemiology

  • Bimodal distribution
    • children <1 year
    • older adults >60 years
  • Generalized convulsive status epilepticus
    • Most frequent type
    • Fatal type of status epilepticus
    • Incidence rate: 7 out of100,000
    • 20% death rate
    • Death rate is higher in the elder people about 30-70%

Etiology

Common cause of Status epilepticus in patients

  • With prior history of epilepsy
    • Withdrawal of anticonvulsant drugs
    • Non-adherence to anticonvulsant drugs
  • With or without prior history of epilepsy
    • Stroke
    • Hypoxia
    • Alcohol intoxication or withdrawal
    • Metabolic disturbances
  • Less common causes
    • Brain trauma
    • Brain tumor

Specific causes of Status Epilepticus

  • CNS Infections
    • Acute Encephalitis
    • Acute Meningitis
    • Cerebral abscess
  • Cerebrovascular causes
    • Stroke
    • Arteriovenous malformations
    • Subarachnoid haemorrhage
  • History of epilepsy
    • Non-adherence to anti-epileptic drugs
    • Discontinuation of anti-epileptic drugs
  • Metabolic causes
    • Hypoglycaemia
    • Hyperglycaemia
    • Hepatic encephalopathy
    • Hyponatremia
    • Hypocalcemia
    • hypomagnesemia
    • Uremia
  • Tumor
    • Brain tumors
  • Alcohol related/toxic causes
    • Heroine
    • Tetramine
  • Trauma
    • Head trauma
  • Hypoxic conditions
    • Cerebral anoxia
    • Cerebral hypoxia
  • Withdrawal syndromes
    • Alcohol withdrawal
    • Barbiturates withdrawal
    • Benzodiazepines withdrawal
  • Drug overdose
    • use of drugs that lower seizure threshold
    • lithium
    • Theophylline
    • Imipenem
    • Cefepime
    • Quinolone antibiotics
    • Tricyclic antidepressants
    • Bupropion

Classification

Classifying the type of status epilepticus is important in determining
  • Morbidity
  • Aggressiveness of treatment required
It is classified into Convulsive status epilepticus and non-convulsive status epilepticus

Table 1: ILAE Task Force Status Epilepticus Classification

Table 1: ILAE Task Force Status Epilepticus Classification
Title
SEMIOLOGY AXES
ETIOLOGY AXES
EEG AXES
AGE AXES
1-With prominent motor symptoms (Convulsive status epilepticus)        It is associated with or without loss of consciousness       Accounts for 37-70 % of Status epilepticus patients a- Generalized Primary generalized convulsive Secondary generalized convulsive (focal evolve into bilateral generalized) Myoclonic Tonic Clonic Atonic b-Focal Jacksonian status epilepticus Epilepsia partialis continua- preserved awareness Oculoclonic seizures Ictal paresis   2-Without prominent motor symptoms       It includes non-convulsive status epilepticus a-NCSE with coma - life threatening condition b- NCSE without coma   i-Generalized non-convulsive status epilepticus Absence status epilepticus (Typical, atypical or myoclonic)   ii-Focal non convulsive status epilepticus Associated with or without loss of consciousness Intact consciousness- auditory, sensory, gustatory, visual, autonomic or emotional symptoms. Aphasic status epilepticus
1-Known etiology Status epilepticus resulting from known conditions Acute: infections, alcohol or drug intoxication, electrolyte imbalance or stroke   Remote: Post- traumatic status epilepticus or post-stroke patients   Progressive: Structural lesions in the brain such a tumor, dementia   Idiopathic and genetic are not included 2-Unknown etiology
Though evidence-based data is not available to classify. Following criteria can be used 1-Location Generalized pattern Localized pattern Multifocal pattern Bilateral/unilateral 2-Type of pattern Periodic Rhythmic delta wave Spike and wave discharges   3-Morphologic features Sharpness of waves Amplitude that can be absolute or relative Phases: triphasic or diphasic morphology Polarity 4-Time related Frequency Duration Onset Prevalence Dynamic: static, evolving, fluctuations 5-Modulation Stimulus induced epilepticus or spontaneous status epilepticus 6-Effect of medication, if given, on EEG
0-30 days: Neonates- Neonatal epilepsy syndromes 1month- 2 years: Infants- Infantile epilepsy syndromes 2-12 years: Childhood- Autonomic status epilepticus, NCSE in childhood syndromes 12-59: Adolescence and adulthood- Juvenile myoclonic or absence status epilepticus ≥59 Elder population-De novo status epilepticus or myoclonic in Alzheimer's

Clinical features

  • Variable presentation
  • Convulsive status epilepticus patients can present with
    • contraction of muscles/ jerky movements
    • stool or urinary incontinence
    • appearance of foam in the mouth
    • eye deviation
    • confusion
    • altered sensorium
    • memory changes
    • personality changes
    • Non convulsive status epilepticus patients can present with
      • Altered state of consciousness
      • Eye movements such as nystagmus, eye deviation etc.
      • Hiccups
      • Twitching of muscles of extremity or face
      • Absence of prominent motor symptoms
      • Urgent EEG should be done to exclude NCSE.
 

Clinical manifestations depending upon the type of seizure

  • Generalized convulsive status epilepticus
    • Altered consciousness
    • Bilateral tonic stiffness followed by clonic motor stiffnes
    • Usually symmetric motor activity
    • Associated with very high morbidity and mortality
  • Focal motor status epilepticus
    • Motor activity limited to one region of the body
    • Can be easily seen
    • Motor activity can be focal or widespread
    • Consciousness may or may not be lost
  • Myoclonic status epilepticus
    • Usually generalized
    • Recurrent rhythmic or arrhythmic myoclonic motor activity
    • Mostly seen in children
    • Late onset myoclonic SE seen in
      • Down syndrome
      • Alzheimer disease

Diagnosis

  • Diagnosis is made clinically
  • Detailed neurological examination and baseline investigations required to rule out or to make alternate diagnosis
  • In order to diagnose non-convulsive status epilepticus, EEG serves as diagnostic tool.

Lab Investigations


FIRST LINE INVESTIGATIONS

  • Should be performed in every patient as this helps to decide the treatment strategy and to prevent complications
    • Full blood count
      • Abnormal FBC may be a sign of sepsis
    • Sodium, potassium, calcium and magnesium
      • Dyselectrolytemia can provoke seizures
    • Renal function tests
      • Impaired urea and creatinine can precipitate seizure
    • Liver function tests
      • Abnormal LFTs may be a sign of systemic disease or alcohol intoxication
    • Glucose
      • may be normal/hypoglycemic/hyperglycemic
      • Abnormal blood glucose level can precipitate/cause seizure
    • Infectious workup
      • Urine Analysis
      • X-ray Chest
      • Blood Culture

OPTIONAL INVESTIGATIONS

  • Decision should be made by physician according to the history of the patient
    • Coagulation screen
      • Helps to identify coagulopathy
    • Arterial blood gas (ABG)
      • Severe transient changes seen in patients with long standing seizures
    • Anticonvulsant drug levels
      • Subtherapeutic anti-epileptic drug level causes status epilepticus
    • Toxicology screen
      • Blood alcohol screening can be used to know recent alcohol levels in the blood
      • Urine toxicology screen helps to screen the level of illicit drugs in urine
    • Ammonia levels
    • Lactate level
    • Pregnancy test (in child bearing age)
    • Lumbar puncture
      • To rule out meningeal inflammation and infection (lymphocytic pleocytosis, increased protein)

Neurophysiological Studies

Electroencephalography (EEG)
  • Not needed in clinically evident status epilepticus
  • Helpful in diagnosing non-convulsive status epilepticus and excluding dissociative seizures
  • Helps to access effectiveness of treatment after confirmation of diagnosis
  • Continuous EEG should be performed for 24 hours to exclude non-convulsive seizures in patients who
    • do not show clinical improvement within 10 min
    • remain unconscious for > 30 min
  • Essential in differentiating myoclonic SE from nonepileptic myoclonic seizures
  • Myoclonic status epilepticus resulting from anoxia reveals
    • Disrupted flat background EEG changes
    • Associated with a poor outcome
  • EEG findings in non-convulsive status epilepticus
    • Periodic discharges for > 2.5/s (per ACNA 2021)
    • Repeated spike and waves for > 10s
    • Rhythmic delta activity

Neuroimaging

  • A STAT CT is recommended in ALL patients presenting with Status Epilepticus to rule out intracerebral hemorrhage
    • CT head other Indications
      • In patients with focal neurological deficits
      • No prior history of epilepsy
      • In a patient with refractory status epilepticus
      • To rule out any brain pathology
 
Peri-ictical MRI findings
Peri-ictal imaging changes occur in
  • region of the epileptic discharge (local) or
  • in distant structures (remote)
  • Local
    • Unilateral/bilateral diencephalic lesions
    • Pulvinar sign (Figure 1b)
    • Cerebellar diaschisis (Figure1c)
    • Splenium abnormalities
    • Posterior leukoencephalopathy
    • Hippocampal swelling
  • Remote
    • Mass effect
    • Sulcal effacement
    • Focal cortical lesions
    • Increased T2 signal
    • Diffusion changes (Figure 1a)
    • Blood brain barrier breakdown
    • Contrast enhancement
    • Increased vessel caliber/flow
    • Increased perfusion of inflammatory lesions
Knowledge of these findings is important because
  • Elucidate the pathophysiology of epileptic seizures
  • May be confused with focal pathology
    • brain tumor
    • stroke
    • encephalitis
  • May be helpful in surgical planning
 

Figure 1A: MR Finding of Status Epilepticus (DWI)

notion image
i) Seizure related restricted diffusion: shows seizure related right hippocampal and thalamus diffusion restriction
notion image
ii) Pulvinar sign: Bilateral restricted diffusion of both thalamus
Source: Di Muzio, B., Saber, M. Status epilepticus. Reference article, Radiopaedia.org. (accessed on 23 Sep 2021) https://radiopaedia.org/articles/33415

Figure 1B: MR Finding of Status Epilepticus (T2)

notion image
notion image
C) Crossed Cerebellar Diaschisis: Hypointensity in left corona radiata and insula along with right cerebellar hemisphera atrophy.
Source: Macagnan, M. Crossed cerebellar diaschisis. Case study, Radiopaedia.org. (accessed on 23 Sep 2021) https://radiopaedia.org/cases/47317

Differential diagnosis

  • Psychogenic status epilepticus
  • Delirium
  • Vasovagal syncope
  • Cardiac syncope
  • Coma

Management

Further Reading

  • Brophy, Gretchen M et al. “Guidelines for the evaluation and management of status epilepticus.” Neurocritical care vol. 17,1 (2012): 3-23. doi:10.1007/s12028-012-9695-z
  • Rossetti, Andrea O et al. “A randomized trial for the treatment of refractory status epilepticus.” Neurocritical care vol. 14,1 (2011): 4-10. doi:10.1007/s12028-010-9445-z

Bibliography

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  • Trinka E, Cock H, Hesdorffer D, et al. A definition and classification of status epilepticus--Report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia 2015; 56:1515.
  • R.F.M. Chin, B.G.R. Neville, R.C. ScottA systematic review of the epidemiology of status epilepticus Eur J Neurol, 11 (December (12)) (2004), pp. 800-810
  • R.J. DeLorenzo, W.A. Hauser, A.R. Towne, J.G.Boggs, J.M. Pellock, L. Penberthy, et al.A prospective, population-based epidemiologic study of status epilepticus in Richmond, Virginia Neurology, 46 (April (4)) (1996), pp. 1029-1035
  • G. Logroscino, D.C. Hesdorffer, G. Cascino, J.F. Annegers, W.A. HauserShort-term mortality after a first episode of status epilepticus Epilepsia, 38 (December (12)) (1997), pp. 1344-1349
  • G. Logroscino, D.C. Hesdorffer, G. Cascino, W.A. Hauser, A. Coeytaux, B. Galobardes, et al.Mortality after a first episode of status epilepticus in the United States and Europe Epilepsia (2005), pp. 46-48
  • Sheth RD, Gidal BE. Intravenous valproic acid for myoclonic status epilepticus. Neurology. 2000 Mar 14;54(5):1201. doi: 10.1212/wnl.54.5.1201. PMID: 10720302.
  • Shaner, D M et al. “Treatment of status epilepticus: a prospective comparison of diazepam and phenytoin versus phenobarbital and optional phenytoin.” Neurology vol. 38,2 (1988): 202-7. doi:10.1212/wnl.38.2.202
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  • Bellante, Flavio et al. “Midazolam and thiopental for the treatment of refractory status epilepticus: a retrospective comparison of efficacy and safety.” Journal of neurology vol. 263,4 (2016): 799-806. doi:10.1007/s00415-016-8074-7
  • Ulvi H, Yoldas T, Müngen B, Yigiter R. Continuous infusion of midazolam in the treatment of refractory generalized convulsive status epilepticus. Neurol Sci. 2002 Oct;23(4):177-82. doi: 10.1007/s100720200058. PMID: 12536286.
  • Lv, R.-J., Wang, Q., Cui, T., Zhu, F., & Shao, X.-Q. (2017). Status epilepticus-related etiology, incidence and mortality: A meta-analysis. Epilepsy Research, 136, 12–17.doi:10.1016/j.eplepsyres.2017.07.006
  • Rossetti AO, Logroscino G, Bromfield EB. Refractory status epilepticus: effect of treatment aggressiveness on prognosis. Arch Neurol. 2005 Nov;62(11):1698-702. doi: 10.1001/archneur.62.11.1698. Erratum in: Arch Neurol. 2006 Oct;63(10):1482. PMID: 16286542.
  • Trinka E, Höfler J, Zerbs A. Causes of status epilepticus.Epilepsia. 2012 Sep;53 Suppl 4:127-38.
  • Walker M. Status epilepticus: an evidence based guide. BMJ. 2005 Sep 24;331(7518):673-7.
  • Von Oertzen J, Cock HR. Testing blood and CSF in people with epilepsy: a practical guide. Epileptic Disord. 2020; In press.
  • Egawa, S., Hifumi, T., Nakamoto, H., Kuroda, Y., & Kubota, Y. (2020). Diagnostic Reliability of Headset-Type Continuous Video EEG Monitoring for Detection of ICU Patterns and NCSE in Patients with Altered Mental Status with Unknown Etiology. Neurocritical Care, 32(1), 217–225. https://doi.org/10.1007/s12028-019-00863-9
  • Van Putten, M. J. A. M., & Hofmeijer, J. (2016). EEG monitoring in cerebral ischemia: Basic concepts and clinical applications. Journal of Clinical Neurophysiology, 33(3), 203–210.
 
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