Case Vignettes in Neurology

PATIENT CASE STUDIES

Case 22 3/4/99 Seizures and epilepsy
Case discussion This is a 23 year old right-handed woman with a history of seizures since age 10. Her seizures were initially characterized by brief staring. Then, at about age 14, she developed generalized tonic-clonic seizures, most of which occurred upon awakening. She has not had one of these seizures for the past 5 years. Her husband describes her present seizures as quiet, unresponsive staring associated with eye fluttering. These seizures last about 10 seconds and occur at a frequency of 1-3 per week, Upon further questioning, the patient admits to occasional involuntary jerking of one or both arms, such tht she has dropped a carton of milk or a glass on the floor. These jerks of the arm usually occur upon awakening and are particulary frequent if she is feeling tired. During the teen years, the generalized tonic-clonic seizures were often preceded by these jerking movments. The patient denies a family history of epilepsy. There is no history of head trauma, encephalitis, or meningitis, or febrile confusions. Her work-up to date includes a routine EEG revealing brief bursts of 4-5 Hz spike and polyspike and wave activity. She had a 24 hour ambulatory EEG during which 2 typical staring seizures were captured, but were not assocated with electrographic changes. She was treated with valproic acid (Depakote) 1000 mg TID and primidone (Mysoline) 550 mg qd on which she was notably ‘spacey’ and with poor seizure control. Hence, primidone (Mysoline) was tapered. Three weeks later, she was admitted to the hospital with an upper GI bleed. Hemoglobin was 8g/dL and platelet count was 77K. She was transfused with 2 units of packed RBC. Valproic acid was tapered. Four weeks after discharge, the patient was brought to the ER by her husband as she was having about one staring seizure every five minutes for the past one day. Upon admission, frequent myoclonic jerks of the upper and lower extremities were noted. EEG demonstrated minimal slowing of the background and frequent generalized fast spike and slow wave activity which temporally correlated with jerking movemens. The paitent was subsequently treated with valproic acid 750 mg tid with a serum level of 90. However, on the 7th day of hospitalization, she had a witnessed generalized seizure. Phenytoin (Dilantin) 300 mg qD was added to the valproic acid (Depakote). No further staring seizures, jerking movements or generalized seizures were observed and the patient was discharged from the hospital.
Summarize the Case in 1-2 sentences. A 23 y/o woman presents with frequent staring seizures with myoclonic jerks for the past day. She has a past history of tonic clonic and absence seizures since childhood, and she has recently experienced anemia due to an upper GI bleed. There is no history of trauma or infection. good, what is the age of onset Discuss lesion localization on the basis of the physical examination. Physical exam showed bilateral myoclonic jerks in upper and lower extremities correlated with EEG fast spike and slow wave activity. The abnormal electrical discharge involves extensive areas of both cerebral hemispheres. the eeg is not part of the physical exam; the localization is the cerebral cortex Discuss underlying pathogenesis on the basis of clinical course. Episodes are sudden in onset and course suggesting paroxysmal electrical or vascular phenomena. good Indicate one likely clinical diagnosis. List (or classify) alternative diagnoses. Absence seizure exacerbated by anemia. Ddx of seizure: metabolic disturbance: decreased glucose toxin: lead, EtOH, cocaine hypoxia: TIA, syncope AV malformation microscars in brain paranchyma good try; however absence seizures do not cause myoclonic jerks and the age of onset suggests juvenile myoclonic epilepsy Indicate 2 ancillary tests that would assist in confirming or refuting the clinical diagnosis. Indicate the test results that would confirm the clinical diagnosis. EEG would show 3Hz bilateral discharge for 5-10 sec. CBC and stool guiac to evaluate anemia and continued GI bleed. Imaging studies (CT/MRI/PET) to indicate structural or functional abnormality. restrict your answer to the question (2 tests) the frequency of the spike and wave is 4-6 irregular in JME (page 151 collins) imaging studies would be done to refute the dx of JME as the mri is normal in this condition. Indicate complications of the disease and ancillary tests that would help evaluate them. Status epilepticus is a condition in which seizures follow each other so closely that they overlap. This can cause permenant brain damage due to hypoxia, hyperthermia, or changes in blood flow. Precipitants of status epilepticus include withdrawel of EtOH/drugs in a habitual user, cerebral infection, trauma, and neoplasm. It would be helpful to educate the patient about this condition so that she could inform people close to her that such an event is a medical emergency. Many complications result from drug toxicity: Valproic acid is hepatotoxic. LFTs should be followed in this patient. Phenytoin can cause seizures if stopped abruptly and can also cause additional neurologic symptoms because it can interfere with B12 metabolism. B12 levels should be monitored. Pregnancy is a concern in our patient. Phenytoin induces p450 hepatic enzymes to decrease many drug levels including oral contraceptives. Pregnancy itself increases seizure frequency. In addition, many antiepileptic drugs are teratogenic. For example, phenytoin can cause fetal hydantoin syndrome. A pregnancy test may be indicated. Valproic acid metabolism may be increased because phenytoin induces liver metabolism. Levels of both these drugs should be monitored. (Primidone is ineffective in absence seizures and has side effects similar to phenobarbital. It is unclear to us why this patient was treated with primidone when she presented with an absence seizure.) answer on the long side, if you list the complications I will be able to read your answer easier. I am not aware that phenytoin interferes with b12 metabolism. It can cause megaloblastic anemia that usually responds to folate. Discuss how the underlying pathophysiology is relevant in the management of this patient. Absence seizures may result from interaction between GABAB receptors, T-type Ca2+ channels, and K+ channels in the thalamus. This interaction results in oscillatory rhythms in circuits connecting the thalamus and cortex. Blocking the T-type channels with valproic acid or ethosuximide interrupts the oscillations to prevent electrical propagation. good answer. If your diagnosis had been JME, than valproic acid, a GABA agonist, may be effective for the 3 types of seizures these patients get, i.e the absence, the myoclonic, and the generalized tonic clonic seizures.. JME is a genetically determined disease whose cause has not yet been ascertained. It is linked to the JME-1 locus on the short arm of chromosome 6.

Case 22 3/4/99 Seizures and epilepsy

Case discussion

This is a 23 year old right-handed woman with a history of seizures since age 10. Her seizures were initially characterized by brief staring. Then, at about age 14, she developed generalized tonic-clonic seizures, most of which occurred upon awakening. She has not had one of these seizures for the past 5 years.

Her husband describes her present seizures as quiet, unresponsive staring associated with eye fluttering. These seizures last about 10 seconds and occur at a frequency of 1-3 per week, Upon further questioning, the patient admits to occasional involuntary jerking of one or both arms, such tht she has dropped a carton of milk or a glass on the floor. These jerks of the arm usually occur upon awakening and are particulary frequent if she is feeling tired. During the teen years, the generalized tonic-clonic seizures were often preceded by these jerking movments.

The patient denies a family history of epilepsy. There is no history of head trauma, encephalitis, or meningitis, or febrile confusions.

Her work-up to date includes a routine EEG revealing brief bursts of 4-5 Hz spike and polyspike and wave activity. She had a 24 hour ambulatory EEG during which 2 typical staring seizures were captured, but were not assocated with electrographic changes.

She was treated with valproic acid (Depakote) 1000 mg TID and primidone (Mysoline) 550 mg qd on which she was notably ‘spacey’ and with poor seizure control. Hence, primidone (Mysoline) was tapered. Three weeks later, she was admitted to the hospital with an upper GI bleed. Hemoglobin was 8g/dL and platelet count was 77K. She was transfused with 2 units of packed RBC. Valproic acid was tapered. Four weeks after discharge, the patient was brought to the ER by her husband as she was having about one staring seizure every five minutes for the past one day.

Upon admission, frequent myoclonic jerks of the upper and lower extremities were noted. EEG demonstrated minimal slowing of the background and frequent generalized fast spike and slow wave activity which temporally correlated with jerking movemens. The paitent was subsequently treated with valproic acid 750 mg tid with a serum level of 90. However, on the 7th day of hospitalization, she had a witnessed generalized seizure. Phenytoin (Dilantin) 300 mg qD was added to the valproic acid (Depakote). No further staring seizures, jerking movements or generalized seizures were observed and the patient was discharged from the hospital.

Summarize the Case in 1-2 sentences.

A 23 y/o woman presents with frequent staring seizures with myoclonic jerks for the past day. She has a past history of tonic clonic and absence seizures since childhood, and she has recently experienced anemia due to an upper GI bleed. There is no history of trauma or infection.

good, what is the age of onset

Discuss lesion localization on the basis of the physical examination.

Physical exam showed bilateral myoclonic jerks in upper and lower extremities correlated with EEG fast spike and slow wave activity. The abnormal electrical discharge involves extensive areas of both cerebral hemispheres.

the eeg is not part of the physical exam; the localization is the cerebral cortex

Discuss underlying pathogenesis on the basis of clinical course.

Episodes are sudden in onset and course suggesting paroxysmal electrical or vascular phenomena.

good

Indicate one likely clinical diagnosis. List (or classify) alternative diagnoses.

Absence seizure exacerbated by anemia.
Ddx of seizure: metabolic disturbance: decreased glucose
toxin: lead, EtOH, cocaine
hypoxia: TIA, syncope
AV malformation
microscars in brain paranchyma

good try; however absence seizures do not cause myoclonic jerks and the age of onset suggests juvenile myoclonic epilepsy

Indicate 2 ancillary tests that would assist in confirming or refuting the clinical diagnosis. Indicate the test results that would confirm the clinical diagnosis.

EEG would show 3Hz bilateral discharge for 5-10 sec.
CBC and stool guiac to evaluate anemia and continued GI bleed. Imaging studies (CT/MRI/PET) to indicate structural or functional abnormality.

restrict your answer to the question (2 tests) the frequency of the spike and wave is 4-6 irregular in JME (page 151 collins) imaging studies would be done to refute the dx of JME as the mri is normal in this condition.

Indicate complications of the disease and ancillary tests that would help evaluate them.

Status epilepticus is a condition in which seizures follow each other so closely that they overlap. This can cause permenant brain damage due to hypoxia, hyperthermia, or changes in blood flow. Precipitants of status epilepticus include withdrawel of EtOH/drugs in a habitual user, cerebral infection, trauma, and neoplasm. It would be helpful to educate the patient about this condition so that she could inform people close to her that such an event is a medical emergency. Many complications result from drug toxicity: Valproic acid is hepatotoxic. LFTs should be followed in this patient. Phenytoin can cause seizures if stopped abruptly and can also cause additional neurologic symptoms because it can interfere with B12 metabolism. B12 levels should be monitored.

Pregnancy is a concern in our patient. Phenytoin induces p450 hepatic enzymes to decrease many drug levels including oral contraceptives. Pregnancy itself increases seizure frequency. In addition, many antiepileptic drugs are teratogenic. For example, phenytoin can cause fetal hydantoin syndrome. A pregnancy test may be indicated. Valproic acid metabolism may be increased because phenytoin induces liver metabolism. Levels of both these drugs should be monitored. (Primidone is ineffective in absence seizures and has side effects similar to phenobarbital. It is unclear to us why this patient was treated with primidone when she presented with an absence seizure.)

answer on the long side, if you list the complications I will be able to read your answer easier. I am not aware that phenytoin interferes with b12 metabolism. It can cause megaloblastic anemia that usually responds to folate.

Discuss how the underlying pathophysiology is relevant in the management of this patient.

Absence seizures may result from interaction between GABAB receptors, T-type Ca2+ channels, and K+ channels in the thalamus. This interaction results in oscillatory rhythms in circuits connecting the thalamus and cortex. Blocking the T-type channels with valproic acid or ethosuximide interrupts the oscillations to prevent electrical propagation.

good answer. If your diagnosis had been JME, than valproic acid, a GABA agonist, may be effective for the 3 types of seizures these patients get, i.e the absence, the myoclonic, and the generalized tonic clonic seizures.. JME is a genetically determined disease whose cause has not yet been ascertained. It is linked to the JME-1 locus on the short arm of chromosome 6.