Status Epilepticus: Classification, Clinical Features, and Diagnosis

Classifying the type of status epilepticus is important in determining morbidity and aggressiveness of treatment required. Clinical manifestations vary according to the type of seizure the patient experiences and yet diagnosis is made clinically based on those clinical manifestations. This chapter will help you understand the classification and how to diagnose patient based on clinical features.

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 stiffness
    • 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)

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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
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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

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