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Introduction
1. Anatomy
2. Microbiology
3. Physiology
4. Pathology
4.1 General pathology
4.2 Central and peripheral nervous system
4.2.1 Cerebrovascular disorders
4.2.2 Pathophysiology
4.2.3 Trauma to the CNS
4.2.4 Increased intracranial pressure
4.2.5 Neurodegenerative disorders and dementia
4.2.6 Seizure disorders
4.2.7 Disorders associated with headache
4.2.8 Neuropathies
4.2.9 Sleep disorders
4.2.10 Movement disorders
4.2.11 Metabolic and demyelinating disorders
4.2.12 Neoplasms
4.2.13 Congenital disorders
4.2.14 Spinal cord disorders
4.2.15 Additional information
4.3 Cardiovascular system
4.4 Respiratory system
4.5 Hematology and oncology
4.6 Gastrointestinal pathology
4.7 Renal, endocrine and reproductive system
4.8 Musculoskeletal system
5. Pharmacology
6. Immunology
7. Biochemistry
8. Cell and molecular biology
9. Biostatistics and epidemiology
10. Genetics
11. Behavioral science
Wrapping up
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4.2.6 Seizure disorders
Achievable USMLE/1
4. Pathology
4.2. Central and peripheral nervous system

Seizure disorders

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A seizure is a temporary dysfunction of the brain caused by an abnormal, excessive, synchronous neuronal discharge. It can present as changes in consciousness and behavior, or as abnormal motor, sensory, autonomic, or cognitive function.

Some symptoms may warn that a seizure is about to start. These prodromal symptoms (often called an aura) can include a sense of déjà vu, fear, or abnormal smells.

Epilepsy is a disease of the brain that predisposes a person to recurrent unprovoked seizures.

The revised definition of status epilepticus is:

  • Seizure with 5 minutes or more of continuous clinical and/or electrographic seizure activity, or
  • Recurrent seizure activity without recovery between seizures.

Causes of seizures

  • High fever
  • Hyponatremia, diuretic use, hypernatremia, hypercalcemia
  • Medications like bupropion, MAOI, SSRI, TCAs, INH, lidocaine, theophylline, tramadol, antipsychotics (chlorpromazine, clozapine)
  • Head trauma, previous scarring
  • Brain tumors
  • Recreational drugs like cocaine, amphetamines
  • Alcohol abuse, alcohol withdrawal
  • Epilepsy
  • CNS infections like meningitis, encephalitis
  • Hepatic encephalopathy
  • Stroke, SAH
  • Hypoxia
  • Hypoglycemia, metabolic disorders

Types of seizures

Seizure type Symptoms
Generalized (affect both sides of the brain)
Absence or Petit Mal Staring blankly into space; rapid blinking, head nodding
Tonic-clonic or Grand Mal or Jacksonian Loss of consciousness, falls, crying out, muscle jerks or spasms, tongue bite, lose bowel or bladder control, frothing, post ictal disorientation, stiffening followed by jerking
Focal or partial (localized to one area of the brain)
Simple partial Twitching, change in sensation like strange taste or smell
Complex partial or dyscognitive Confusion, unable to answer questions or follow directions, automatisms like lip smacking, grimacing, often preceded by aura, amnesia, postictal disorientation
Secondary generalized Focal followed by generalized seizure

A tonic-clonic seizure has two phases:

  • Tonic phase: stiffening
  • Clonic phase: rhythmic jerking

These seizures start in the primary motor or premotor cortex.

Focal seizures are classified by whether consciousness is affected:

  • Simple: no loss or disturbance of consciousness
  • Complex (dyscognitive): consciousness is impaired or lost

Absence seizures may be typical (petit mal) or atypical (Lennox-Gastaut syndrome). Myoclonic seizures may be focal or generalized.

The clinical manifestations of a focal seizure depend on the cortical area involved. For example:

  • Occipital lobe: visual phenomena
  • Precentral gyrus: rhythmic clonic or tonic motor activity
  • Postcentral gyrus: sensory symptoms such as paresthesias
  • Auditory cortex: hearing music, voices, or roaring sounds

Epileptic spasms are a type of seizure disorder characterized by sudden extension or flexion of the extremities, held for several seconds, and recurring in clusters (e.g., infantile spasms).

Temporal lobe epilepsy is the most common cause of epilepsy. It is a partial complex or psychomotor epilepsy. These seizures often begin with a visceral sensation or other aura, followed by impaired consciousness, automatic motor activities, or convulsions. The aura may be visual, olfactory, cognitive (such as a sense of déjà vu), sensory, or emotional (such as anger or aggression).

EEG localizes the epileptogenic focus in the medial portion of the temporal lobe. Hippocampal sclerosis and neuronal loss by excitotoxicity is seen. Impaired GABAergic inhibition, enhanced synaptic excitation via axonal sprouting, and changes in ion channel distribution and function have all been implicated in the pathophysiology of temporal lobe epilepsy.

Febrile seizures are seen in children aged 6 months to 5 years of age.

  • Simple febrile seizures are brief (<15 min), generalized, and do not recur within 24 h of the first one.
  • Complicated febrile seizures are either prolonged (>15 min), have focal components (e.g., begin on one side of the body or involve lateralized eye deviation), or recur within 24 h.

Febrile seizures may predispose to temporal lobe epilepsy in adult life. Any cause of fever, including viral infections such as Roseola and influenza, and MMR and DPT vaccinations, can precipitate febrile seizures in susceptible individuals. Often, a family history of febrile seizures is present.

Seizures are caused by an imbalance between excitation (glutamate mediated) and inhibition (GABA mediated) in the brain due to genetic or acquired factors. Under normal circumstances, excitatory synaptic activity is tightly regulated by inhibitory interneurons. Genetic or acquired factors that disrupt this regulation can cause cortical networks to become hyperexcitable. Furthermore, neuropeptides released at synapses facilitate the spread of seizure.

Mutations may be present in:

  • Ion channels like voltage gated K+ channels
  • Neuronal Na+ channels (SCN1A mutations)
  • GABA receptors

For example, in generalized seizures, the defect may be abnormal sodium channels in cortical interneurons, allowing increased firing of downstream excitatory pyramidal neurons that are released from inhibitory control.

The pathophysiology of absence seizures involves altered function of thalamocortical circuits, with thalamic relay neurons firing abnormally due to calcium channel dysfunction. Mitochondrial diseases and autoantibodies are seen in some seizure disorders. Prolactin levels are elevated after generalized seizures.

In pseudoseizures, clinically seizure-like symptoms are seen without any EEG changes. About 10% of adults with epilepsy have bipolar disorder, and up to 30% have depression. Persons with epilepsy are also at increased risk for early mortality and sudden unexplained death in epilepsy (SUDEP).

EEG in epilepsy

Epilepsy type EEG pattern
Infantile spasms, West syndrome Diffuse, chaotic giant waves with multifocal spikes and sharp waves (hypsarrhythmia)
Absence seizures 3 Hz spike and wave pattern
Myoclonic epilepsy Polyspike and wave pattern
Generalized tonic-clonic Generalised polyspikes in tonic phase followed by generalised spike-wave pattern in clonic phase

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