AssessmentsSeizures: Pathology review
USMLE® Step 1 style questions USMLE
A 23-year-old woman is brought to the emergency department by ambulance because her body started shaking violently 10 minutes ago at a nearby bus stop. She was waiting for a bus with her partner when she suddenly fell down and started having stiffening and jerking movements involving all four extremities. Past medical history is significant for epilepsy, for which the patient takes lamotrigine. The partner notes the patient recently started taking a combined oral contraceptive pill. Her temperature is 37.5°C (99.5°F), pulse is 112/min and regular, respirations are 22/min and blood pressure is 108/68 mmHg. The patient is unable to respond to vocal commands. Physical examination shows ongoing symmetric rhythmic jerking of the limbs. After appropriate supportive treatment, the patient is given a drug intramuscularly, after which the jerking subsides. Which of the following best describes the mechanism of action of the drug administered?
Contributors:Elizabeth Nixon-Shapiro, MSMI, CMI, Tanner Marshall, MS, Rachel Yancey, Maria Emfietzoglou, MD
On the neurology ward, a 7-year old male, called Stefan, is brought by his mother. His mother is worried because he has several episodes every day where he loses consciousness for a few seconds. His teacher also complains that she often catches him daydreaming during the lesson. Next to Stefan, there’s a 17-year old male, called Jacob, who seems sluggish and tired. His friends brought him because he suddenly started “shaking and jerking” and he lost consciousness for about two minutes. His medical history is otherwise insignificant. Now, there’s also an 11-year old female, called Megan, who also seems lethargic. Her father is very upset because he witnessed an episode of twitching of her left foot that lasted a few minutes. Megan was unconscious and has no memory of the event. Finally, there’s a 19-year old female, called Joanna, that has had repetitive episodes of sudden and rapid jerking movements with loss of consciousness for the past few months. They usually occur when she wakes up in the morning and especially during periods of sleep deprivation.
Okay, so all of them had a seizure episode. A seizure is a paroxysmal motor, sensory or autonomic event that occurs due to abnormal, excessive and synchronous electrical discharges from neurons in the brain. Seizures usually last less than 5 minutes. If it lasts more than 5 minutes, it’s called status epilepticus. Epilepsy is a chronic disease of the brain that predisposes an individual to having recurrent unprovoked seizures; that is seizures without a clear triggering cause. Epilepsy is typically diagnosed when an individual has two or more unprovoked seizures separated by at least twenty-four hours.
Okay, now seizures are broadly classified into two types, generalized and focal seizures. Generalized seizures arise from both cerebral hemispheres at the same time, while focal seizures arise from specific areas in one cerebral hemisphere. However, focal seizures can spread to both cerebral hemispheres, causing a generalized seizure. When this happens, it’s appropriately called secondary generalization of a focal seizure.
Okay, now let’s take a closer look at the different subtypes of generalized seizures. Generalized seizures are subclassified into motor and non-motor seizures. Regardless of the subtype, generalized seizures almost always cause a sudden impairment of consciousness. Generalized motor seizures include tonic, clonic, tonic-clonic, atonic, and myoclonic seizures. Tonic seizures involve sudden stiffening of the muscles, while clonic seizures involve rhythmic twitching of the muscles. However, these clinical features are usually combined, so individuals commonly have a tonic-clonic seizure. In a generalized tonic-clonic seizure, a person may have a sudden contraction of their vocal cord muscles, causing them to involuntarily scream or cry during a seizure. Contraction of the ocular muscles can cause uprolling of the eyes. Contraction of the oropharyngeal muscles can impair swallowing, causing respiratory secretions to pool in the oropharynx. Contraction of the jaw muscles may cause the individual to bite on their tongue. Individuals with tonic-clonic seizures may also develop urinary or fecal incontinence. After the tonic-clonic seizure ends, individuals enter a period called the post-ictal phase, during which the individual’s consciousness is still impaired for minutes to hours, so they seem sluggish and tired or hard to wake up. So on the exam, look for these subtle clues that indicate a post-ictal phase. Next are myoclonic seizures. For the test, remember that myoclonic seizures involve sudden, rapid, muscle contractions. This sounds a lot like clonic seizures, but the key difference is that in myoclonic seizures, the contractions are much faster, occurring at a rate of 0.1 seconds, whereas in clonic seizures, the contractions occur at a rate of about 1 to 2 seconds. Myoclonic seizures typically occur in the morning and are usually triggered by stress or sleep deprivation, and that’s something you also have to know for the exams! Alright, now atonic seizures translates to “no muscle tone”. Therefore they are characterized by sudden loss of postural muscle tone lasting 1 to 2 seconds, causing the individual to collapse to the ground out of the blue. Alright, moving on to the other arm of generalized seizures, there are the generalized non-motor seizures. These are called absence seizures and they are very high yield. They are commonly found in children and adolescents. Episodes are characterized by sudden, brief loss of consciousness for seconds to minutes without any change in the individual’s muscle tone. So, they could be sitting in class listening to a lecture and suddenly lose consciousness without falling down. Unfortunately, episodes can occur dozens or even hundreds of times per day, and are classically described by parents and teachers as “staring into space”, or “daydreaming”, or being “inattentive”. In fact, many children with absence seizures are actually misdiagnosed with attention-deficit hyperactivity disorder, because teachers often presume that a child is just not paying attention.
Okay, now another high yield topic is focal seizures, previously called partial seizures. Focal seizures are classified into those that do not impair consciousness,, and those that impair consciousness. Focal seizures that impair consciousness are also followed by a post-ictal phase, whereas focal seizures that didn’t affect consciousness do not have a postictal phase. Now, focal seizures can be motor, sensory, or autonomic, depending on the area of the cerebral cortex involved. For example, a focal seizure involving the primary motor cortex may cause tonic or clonic movements of the contralateral extremity, whereas a focal seizure involving the occipital cortex may cause someone to see flashing lights. Sometimes, focal seizures may begin as subtle neurological symptoms called auras. During an aura, individuals may exhibit subtle muscle movements called automatisms, such as chewing, lip smacking, or rapid blinking of the eyes. Other interesting forms of aura include smelling unusual odors like kerosene, a rising sensation in abdomen, or even feelings of fear or deja vu. Also, an interesting phenomenon that occurs after focal motor seizures is Todd’s paralysis, which describes a temporary paralysis of the affected extremity. Alright, now it might be difficult to know if a seizure was a generalized tonic-clonic right from the beginning, or if it was a focal seizure that secondarily generalized. However, a history of an aura, unilateral shaking, turning of the head to one side or Todd’s paralysis is a clue it may have been a focal seizure that secondarily generalized. Take that with a grain of salt though, because the absence of these historical features does not adequately exclude a focal seizure.
Okay, now a special subtype of seizures that occurs in young children between the ages of 6 months and 5 years are febrile seizures. These only happen when the child develops a fever, and they can be generalized or focal. Because of this, febrile seizures are classified differently, and include simple and complex febrile seizures. Simple febrile seizures are usually generalized, last less than 15 minutes, and do not happen again within 24 hours. Complex febrile seizures are usually focal in onset, last more than 15 minutes, and often happen more than once in the span of 24 hours. For your exam, remember that infection with human herpes virus 6 or HHV-6 has a particularly high association with febrile seizures. This virus also causes roseola infantum, a disease characterized by the development a high grade fever for about 3 to 5 days, then the fever goes away and a maculopapular rash appears on the trunk and spreads to the extremities. So remember, fever first, rash later. Diagnostic investigations focus on looking for the cause of fever and excluding serious pathology. For example, a lumbar puncture may be performed to exclude meningitis.
- "Robbins Basic Pathology" Elsevier (2017)
- "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
- "CURRENT Medical Diagnosis and Treatment 2020" McGraw-Hill Education / Medical (2019)
- "DeGowin's Diagnostic Examination, Tenth Edition" McGraw-Hill Education / Medical (2014)
- "Epilepsy" Lippincott Williams & Wilkins (2007)
- "Cochrane Database of Systematic Reviews" ()
- "Ion Channel Genes and Epilepsy: Functional Alteration, Pathogenic Potential, and Mechanism of Epilepsy" Neuroscience Bulletin (2017)
- "The Blood?Brain Barrier and Epilepsy" Epilepsia (2006)