1. First Seizure in Adulthood Diagnosis and Treatment The “bring your pillow to work” lecture Jim Czarnecki, D.O.

2. Introduction

3. Introduction Many diseases can cause paroxysmal clinical events. Correct diagnosis is necessary to provide correct treatment. Many diseases can cause paroxysmal clinical events. Correct diagnosis is necessary to provide correct treatment. If the event is an epileptic seizure, the seizure type and associated clinical, EEG, and neuroimaging findings assist in determining the risk of seizure recurrence and the possible need to begin anticonvulsant therapy. If the event is an epileptic seizure, the seizure type and associated clinical, EEG, and neuroimaging findings assist in determining the risk of seizure recurrence and the possible need to begin anticonvulsant therapy.

4. Introduction The correct diagnosis is often missed. The correct diagnosis is often missed. An acute symptomatic seizure is one that occurs following a recent acute disorder such as a metabolic insult, toxic insult, CNS infection, stroke, brain trauma, cerebral hemorrhage, medication toxicity, alcohol withdrawal, or drug withdrawal. An example of an acute symptomatic seizure is a seizure that occurs within 1 week of a stroke or head injury. An acute symptomatic seizure is one that occurs following a recent acute disorder such as a metabolic insult, toxic insult, CNS infection, stroke, brain trauma, cerebral hemorrhage, medication toxicity, alcohol withdrawal, or drug withdrawal. An example of an acute symptomatic seizure is a seizure that occurs within 1 week of a stroke or head injury.

5. Introduction In 1988, Scheepers et al found 49 patients with an incorrect diagnosis and 26 patient with an uncertain diagnosis among 214 patients with a diagnosis of epilepsy. In 1988, Scheepers et al found 49 patients with an incorrect diagnosis and 26 patient with an uncertain diagnosis among 214 patients with a diagnosis of epilepsy. In a 1999 report, Davidson describes a similar approach to the patient with a first seizure. In a 1999 report, Davidson describes a similar approach to the patient with a first seizure. Is it epilepsy? Is it epilepsy? What kind of epilepsy? What kind of epilepsy? What is the cause? What is the cause?

6. Pathophysiology

7. Pathophysiology - Definitions Definitions Definitions Nonepileptic event – event presumed to be unrelated to abnormal and excessive neuronal discharge. An example is syncope. Decreased cardiac output causes decreased cerebral perfusion, and this results in loss of consciousness. Nonepileptic event – event presumed to be unrelated to abnormal and excessive neuronal discharge. An example is syncope. Decreased cardiac output causes decreased cerebral perfusion, and this results in loss of consciousness.

8. Pathophysiology - Definitions Epileptic seizure – event presumed to result from an abnormal and excessive neuronal discharge. The symptoms are paroxysmal and may include impaired consciousness and motor, sensory, autonomic, or psychic events perceived by the subject or an observer. Epileptic seizure – event presumed to result from an abnormal and excessive neuronal discharge. The symptoms are paroxysmal and may include impaired consciousness and motor, sensory, autonomic, or psychic events perceived by the subject or an observer.

9. Pathophysiology – Definitions Epilepsy occurs when 2 more epileptic seizures occur unprovoked by any immediately identifiable cause. The seizures must occur more than 24 hours apart. Epilepsy occurs when 2 more epileptic seizures occur unprovoked by any immediately identifiable cause. The seizures must occur more than 24 hours apart. In studies, an episode of status epilepticus is considered a single seizure. Febrile seizures and neonatal seizures are excluded from this category. In studies, an episode of status epilepticus is considered a single seizure. Febrile seizures and neonatal seizures are excluded from this category.

10. Pathophysiology - Definitions Idiopathic epilepsy describes epilepsy syndromes with specific age-related onset, specific clinical and electrographic characteristics, and a presumes genetic mechanism. Idiopathic epilepsy describes epilepsy syndromes with specific age-related onset, specific clinical and electrographic characteristics, and a presumes genetic mechanism. Epileptic seizures are classified as Epileptic seizures are classified as cryptogenic cryptogenic symptomatic symptomatic

11. Pathophysiology - Definitions Cyrptogenic seizure is a seizure of unknown etiology. This type of seizure is not associated with a prior CNS insult known to increase the risk of developing epilepsy. It does not conform to the criteria for the idiopathic or symptomatic categories. Cyrptogenic seizure is a seizure of unknown etiology. This type of seizure is not associated with a prior CNS insult known to increase the risk of developing epilepsy. It does not conform to the criteria for the idiopathic or symptomatic categories. Previous studies use the term idiopathic to describe a seizure of unknown etiology. Previous studies use the term idiopathic to describe a seizure of unknown etiology.

12. Pathophysiology - Definitions Symptomatic seizure is a seizure caused by a previously known or suspected disorder of the CNS. This type of seizure is associated with a prior CNS insult known to increase the risk of developing epilepsy. Symptomatic seizure is a seizure caused by a previously known or suspected disorder of the CNS. This type of seizure is associated with a prior CNS insult known to increase the risk of developing epilepsy.

13. Pathophysiology - Definitions A remote symptomatic seizure occurs more than 1 week following a disorder that is known to increase the risk of developing epilepsy. The seizure may occur a long time after the disorder. These disorders may produce static or progressive brain lesions. An example of a remote symptomatic seizure is a seizure that first occurs 6 months following a traumatic brain injury or stroke. A remote symptomatic seizure occurs more than 1 week following a disorder that is known to increase the risk of developing epilepsy. The seizure may occur a long time after the disorder. These disorders may produce static or progressive brain lesions. An example of a remote symptomatic seizure is a seizure that first occurs 6 months following a traumatic brain injury or stroke.

14. Pathophysiology - Definitions Seizures are also classified as: Seizures are also classified as: Provoked – an acute symptomatic seizure Provoked – an acute symptomatic seizure Unprovoked – a cryptogenic or remote symptomatic seizure Unprovoked – a cryptogenic or remote symptomatic seizure

15. Frequency

16. Frequency In the US: In 1997, it was reported that the annual incidence of adult-onset seizures in the United States is 84 per 100,000 population and that about 6% of the US population experience a nonfebrile seizure sometime during life. In the US: In 1997, it was reported that the annual incidence of adult-onset seizures in the United States is 84 per 100,000 population and that about 6% of the US population experience a nonfebrile seizure sometime during life. Estimates are approximately 50 of each 84 patients develop epilepsy. Estimates are approximately 50 of each 84 patients develop epilepsy.

17. Mortality / Morbidity

18. The patient who develops recurrent unprovoked seizures has the same mortality and morbidity rates as other patients with epilepsy. The patient who develops recurrent unprovoked seizures has the same mortality and morbidity rates as other patients with epilepsy.

19. Race

20. Race Racial differences have not been studied. Racial differences have not been studied.

21. Sex

22. Sex Most authors report a small-to-moderate preponderance of men in their studies of a first seizures in adults. Most authors report a small-to-moderate preponderance of men in their studies of a first seizures in adults.

23. Age

24. Age In a study (Musicco, 1993) of consecutive patients aged 2 years or older, the age distribution for a first unprovoked seizure was the following: In a study (Musicco, 1993) of consecutive patients aged 2 years or older, the age distribution for a first unprovoked seizure was the following: Younger than 16 years – 28% Younger than 16 years – 28% Aged 16-60 years – 66% Aged 16-60 years – 66% Older than 60 years – 6% Older than 60 years – 6%

25. Age Among adults, young adults are affected most often. Among adults, young adults are affected most often. Patients aged 15 years and older, the mean age of first unprovoked seizure was 38 years (Van Donselaar, 1992). Patients aged 15 years and older, the mean age of first unprovoked seizure was 38 years (Van Donselaar, 1992). In a study of patients 16 years and older, the most frequently affected group was aged 20 – 29 years (Hopkins, 1988). In a study of patients 16 years and older, the most frequently affected group was aged 20 – 29 years (Hopkins, 1988).

26. Clinical Aspects

27. History The following information should be obtained in the history: The following information should be obtained in the history: Age Age If a family history of seizures is noted, the clinical epilepsy syndrome of the affected family members should be determined. If a family history of seizures is noted, the clinical epilepsy syndrome of the affected family members should be determined. Ask about a history of any previous provoked seizure. Ask about a history of any previous provoked seizure. Determine if the first seizure was status epilepticus. Determine if the first seizure was status epilepticus.

28. History Ask the time of day of the seizure occurrence. Ask the time of day of the seizure occurrence. Identify any symptoms that may indicate a nonepileptic event, such as convulsive syncope, syncope, transient ischemic attack, transient global amnesia, migraine, sleep disorder, movement disorder, vertigo, or nonepileptic psychogenic seizure (“pseudoseizure”). Identify any symptoms that may indicate a nonepileptic event, such as convulsive syncope, syncope, transient ischemic attack, transient global amnesia, migraine, sleep disorder, movement disorder, vertigo, or nonepileptic psychogenic seizure (“pseudoseizure”).

29. History Because of the frequency with which nonepileptic seizures occur, the first step should be to rule out nonepileptic events. Because of the frequency with which nonepileptic seizures occur, the first step should be to rule out nonepileptic events. Seek a possible etiology (will be covered in the Causes Section). Seek a possible etiology (will be covered in the Causes Section).

30. Physical Exam

31. The neurologic examination should be directed at finding clinical evidence of a focal brain lesion. The neurologic examination should be directed at finding clinical evidence of a focal brain lesion. A general physical examination should be performed to exclude a nonneurologic cause of the seizure. A general physical examination should be performed to exclude a nonneurologic cause of the seizure.

32. Causes

33. Causes Epileptic seizure Epileptic seizure Prenatal, perinatal, or postnatal complications of pregnancy and delivery Prenatal, perinatal, or postnatal complications of pregnancy and delivery Febrile seizure: Distinguish a complex febrile seizure from a simple febrile seizure. Febrile seizure: Distinguish a complex febrile seizure from a simple febrile seizure. Cerebrovascular disease such as cerebral infarction, cerebral hemorrhage, and venous thrombosis Cerebrovascular disease such as cerebral infarction, cerebral hemorrhage, and venous thrombosis CNS infections such as meningitis or encephalitis CNS infections such as meningitis or encephalitis

34. Causes Epileptic seizure (continued): Epileptic seizure (continued): Head Trauma – Is the more significant when it occurs with loss of consciousness lasting longer than 30 minutes, post-traumatic amnesia lasting longer than 30 minutes, focal neurologic findings, or neuroimaging finding suggesting a structural brain injury. Head Trauma – Is the more significant when it occurs with loss of consciousness lasting longer than 30 minutes, post-traumatic amnesia lasting longer than 30 minutes, focal neurologic findings, or neuroimaging finding suggesting a structural brain injury. Neurodegenerative diseases Neurodegenerative diseases Autoimmune disease Autoimmune disease

35. Causes Epileptic seizure (continued): Epileptic seizure (continued): Brain neoplasm Brain neoplasm Genetic diseases Genetic diseases Drug intoxication, drug withdrawal, or alcohol withdrawal Drug intoxication, drug withdrawal, or alcohol withdrawal Metabolic medical disorders such as uremia, hypoglycemia, hyponatremia, and hypocalcemia Metabolic medical disorders such as uremia, hypoglycemia, hyponatremia, and hypocalcemia

36. Causes Nonepileptic events Nonepileptic events Transient ischemic attack Transient ischemic attack Migraine Migraine Sleep disorders Sleep disorders Transient global amnesia Transient global amnesia Movement disorder Movement disorder Paroxysmal vertigo Paroxysmal vertigo Malingering Malingering

37. Causes Nonepileptic events (continued): Nonepileptic events (continued): Convulsive syncope: Decreased cardiac output causes reduced cerebral perfusion with loss of consciousness and convulsive motor activity. Convulsive syncope: Decreased cardiac output causes reduced cerebral perfusion with loss of consciousness and convulsive motor activity. Psychiatric disorders such as conversion disorder (psychogenic seizures, pseudoepileptic seizures, pseudoseizures) Psychiatric disorders such as conversion disorder (psychogenic seizures, pseudoepileptic seizures, pseudoseizures)

38. Differentials

39. Differentials Cardioembolic Stroke Cardioembolic Stroke Chorea Gravidarum Chorea Gravidarum Chorea in Adults Chorea in Adults Complex Partial Seizures Complex Partial Seizures Epilepsia Partialis Continua Epilepsia Partialis Continua Epilepsy, Juvenile Myoclonic Epilepsy, Juvenile Myoclonic Epileptiform Discharges Epileptiform Discharges Essential Tremor First Seizure: Pediatric Perspective Frontal Lobe Epilepsy Hemifacial Spasm Huntinging Disease Migrain Variants Narcolepsy

40. Work Up

41. Lab Studies Metabolic screening for uremia, hypoglycemia, drug intoxications, and electrolyte disorders should be conducted for patients with first seizure who present to the emergency department Metabolic screening for uremia, hypoglycemia, drug intoxications, and electrolyte disorders should be conducted for patients with first seizure who present to the emergency department Other laboratory investigations may be indicated for specific clinical situations. Other laboratory investigations may be indicated for specific clinical situations.

42. Imaging Studies

43. Neuroimaging should be performed because discovery of an epileptogenic lesion can have an impact on the diagnosis, prognosis, and treatment of new-onset seizures. Neuroimaging should be performed because discovery of an epileptogenic lesion can have an impact on the diagnosis, prognosis, and treatment of new-onset seizures. MRI improves diagnostic accuracy. MRI improves diagnostic accuracy. CT scanning might miss surgical remedial brain lesions that would otherwise be detected by MRI. King et al found that CT scanning detected only 12 of the 28 brain lesions that were detected by MRI; 7 of the missed lesions were brain tumors. CT scanning might miss surgical remedial brain lesions that would otherwise be detected by MRI. King et al found that CT scanning detected only 12 of the 28 brain lesions that were detected by MRI; 7 of the missed lesions were brain tumors.

44. Imaging Studies Neuroimaging is unlikely to detect brain lesions in patients with clinical and EEG features of idiopathic generalized epilepsy or benign epilepsy. (King et al found that MRI did not detect any brain lesions in 49 patients with clinical and EEG features of idiopathic generalized epilepsy or in 11 patients with benign epilepsy.) Neuroimaging is unlikely to detect brain lesions in patients with clinical and EEG features of idiopathic generalized epilepsy or benign epilepsy. (King et al found that MRI did not detect any brain lesions in 49 patients with clinical and EEG features of idiopathic generalized epilepsy or in 11 patients with benign epilepsy.)

45. Imaging Studies In 1998, Chadwick and Smith concluded that plausible arguments may be made for obtaining routine early CT scanning and reserving MRI for patients with epilepsy whose seizures are not controlled by antiepileptic drugs. In 1998, Chadwick and Smith concluded that plausible arguments may be made for obtaining routine early CT scanning and reserving MRI for patients with epilepsy whose seizures are not controlled by antiepileptic drugs.

46. Other Tests

47. EEG should be performed within 24 hours of the seizure because it is significantly more sensitive when obtained during the period. If the routine EEG findings are normal, a sleep- deprived EEG should be performed. EEG should be performed within 24 hours of the seizure because it is significantly more sensitive when obtained during the period. If the routine EEG findings are normal, a sleep- deprived EEG should be performed. Standard EEG detects epileptiform discharges in 29% of patients. Standard EEG combined with sleep-deprived EEG shows epileptiform discharges in 48% of patients. Standard EEG detects epileptiform discharges in 29% of patients. Standard EEG combined with sleep-deprived EEG shows epileptiform discharges in 48% of patients.

48. EEG

49. EEG

50. Normal EEG

51. Abnormal EEG

52. EEG – Lead Placement

54. Medical Care

55. Many patients who have a single seizure do not require therapy. Many patients who have a single seizure do not require therapy. The decision to be on therapy is based on a discussion of the risk of seizure recurrence, the effectiveness of treatment, and the adverse medical and socioeconomic effects of anticonvulsant treatment. The decision to be on therapy is based on a discussion of the risk of seizure recurrence, the effectiveness of treatment, and the adverse medical and socioeconomic effects of anticonvulsant treatment.

56. Medical Care Among medically untreated patients in one study (Musicco, 1993), the cumulative 2-year risk of seizure recurrence was 51%. Among medically untreated patients in one study (Musicco, 1993), the cumulative 2-year risk of seizure recurrence was 51%. Risk Factors for recurrent seizures include the following list. Risk Factors for recurrent seizures include the following list.

57. Risk Factors Age younger than 16 years Age younger than 16 years Remote symptomatic seizure Remote symptomatic seizure Seizures occurring between midnight and 8:59 am Seizures occurring between midnight and 8:59 am Prior provoked seizures Prior provoked seizures Remote symptomatic seizure in a patient whose sibling is affect with epilepsy Remote symptomatic seizure in a patient whose sibling is affect with epilepsy

58. Risk Factors Status epilepticus or multiple seizures within 24 hours as the initial remote symptomatic seizure. Status epilepticus or multiple seizures within 24 hours as the initial remote symptomatic seizure. Partial seizures Partial seizures Todd’s paralysis in patients with a remote symptomatic seizure Todd’s paralysis in patients with a remote symptomatic seizure History of neurologic deficit from birth such as cerebral palsy or mental retardation. History of neurologic deficit from birth such as cerebral palsy or mental retardation. Abnormal examination findings in patients without a remote symptomatic seizure Abnormal examination findings in patients without a remote symptomatic seizure

59. Risk Factors CT scan that shows a brain tumor CT scan that shows a brain tumor EEG that shows epileptiform discharges EEG that shows epileptiform discharges

60. Epileptiform Discharges

61. Medical Therapy Immediate anticonvulsant treatment reduces the likelihood of a second seizure by half. Immediate anticonvulsant treatment reduces the likelihood of a second seizure by half. Immediate anticonvulsant treatment does not effect the long-term prognosis for achieving 1- or 2-year seizure-free remission and exposes many patients who would never have a recurrent seizure to anticonvulsant side effects. Immediate anticonvulsant treatment does not effect the long-term prognosis for achieving 1- or 2-year seizure-free remission and exposes many patients who would never have a recurrent seizure to anticonvulsant side effects.

62. Medical Therapy The need for anticonvulsant treatment after two seizures is generally agreed upon. The decision to provide anticonvulsant treatment after one seizure should be individualized. The need for anticonvulsant treatment after two seizures is generally agreed upon. The decision to provide anticonvulsant treatment after one seizure should be individualized. Two situations that are often encountered in clinical practice and should be distinguished are a first seizure and new-onset epilepsy with more than one unprovoked seizure. Two situations that are often encountered in clinical practice and should be distinguished are a first seizure and new-onset epilepsy with more than one unprovoked seizure.

63. Medical Therapy Berg and Shinnar emphasized the need to distinguish between these two entities in clinical studies (Berg, 1991). Berg and Shinnar emphasized the need to distinguish between these two entities in clinical studies (Berg, 1991). Seizure recurrence risk is substantially higher after two or more unprovoked seizures than after just one (Hauser, 1990). Seizure recurrence risk is substantially higher after two or more unprovoked seizures than after just one (Hauser, 1990).

64. Medical Therapy In a 1995 report, Heller et al found that phenytoin, carbamazepine, valproate, and phenobarbital were equally effective in treating newly diagnosed epilepsy and that phenobarbital had more adverse effects. Mattson and coworks found similar results (Mattson, 1985). In a 1995 report, Heller et al found that phenytoin, carbamazepine, valproate, and phenobarbital were equally effective in treating newly diagnosed epilepsy and that phenobarbital had more adverse effects. Mattson and coworks found similar results (Mattson, 1985).

65. Follow-Up

66. Further Inpatient Care

67. Many patients who have a seizure recover spontaneously and fully with normal consciousness after a short time interval. Many patients who have a seizure recover spontaneously and fully with normal consciousness after a short time interval. Patients with incomplete recovery or a prolonged postictal state may require inpatient hospitalization. Patients with incomplete recovery or a prolonged postictal state may require inpatient hospitalization. Inpatient management may be necessary if the clinical course is complicated by other medical problems requiring inpatient management. Inpatient management may be necessary if the clinical course is complicated by other medical problems requiring inpatient management.

68. Further Inpatient Care A short hospitalization may be necessary for patients who are at risk of recurrent seizures and have no adequate supervision at home. A short hospitalization may be necessary for patients who are at risk of recurrent seizures and have no adequate supervision at home. Patients admitted from an emergency department had a 16.8% risk of an early recurrent seizure during their brief hospitalization. Patients admitted from an emergency department had a 16.8% risk of an early recurrent seizure during their brief hospitalization.

69. Medical / Legal Pitfalls

70. Patients who have had a single epileptic seizure are at increased risk of having a second seizure. Patients who have had a single epileptic seizure are at increased risk of having a second seizure. These patients should be informed that they are at increased risk of injury to themselves or others if another seizure occurs. These patients should be informed that they are at increased risk of injury to themselves or others if another seizure occurs. Risk of injury is especially important if patients are driving, operating dangerous machinery, or performing other activities that could put themselves or others at risk. Risk of injury is especially important if patients are driving, operating dangerous machinery, or performing other activities that could put themselves or others at risk.

71. Medical / Legal Pitfalls Counseling patients about driving after a first seizure revolves around 2 issues: Counseling patients about driving after a first seizure revolves around 2 issues: The diagnosis The diagnosis The chance of recurrence The chance of recurrence

72. Medical / Legal Pitfalls Patients with a first epileptic seizure with risk factors such as remote symptomatic etiology or EEG with epileptiform discharges are at higher risk for a second seizure. Patients with a first epileptic seizure with risk factors such as remote symptomatic etiology or EEG with epileptiform discharges are at higher risk for a second seizure. Restrictions of hazardous activity should be more emphatic for these patients. Restrictions of hazardous activity should be more emphatic for these patients.

73. Special Concerns

74. The diagnosis of epilepsy refers to recurrent seizures and cannot be made on the basis of a single episode, even if anticonvulsant treatment is administered. This especially important because of the serious medical, social, and legal consequences surrounding the diagnosis of epilepsy. The diagnosis of epilepsy refers to recurrent seizures and cannot be made on the basis of a single episode, even if anticonvulsant treatment is administered. This especially important because of the serious medical, social, and legal consequences surrounding the diagnosis of epilepsy. The annual cost of misdiagnosis of nonepileptic spells as epileptic seizures is estimated to be between $650 million and $4 billion. The annual cost of misdiagnosis of nonepileptic spells as epileptic seizures is estimated to be between $650 million and $4 billion.

75. Competency Exam

76. Question One 1) All are correct regarding a history of a patient with new onset seizure, except: A) Family history of seizures should be noted B) History of any previous provoked seizure C) Determine if this first seizure was status epilepticus D) Age is noncontributory E) Time of day of the seizure

77. Question One 1) All are correct regarding a history of a patient with new onset seizure, except: A) Family history of seizures should be noted B) History of any previous provoked seizure C) Determine if this first seizure was status epilepticus D) Age is noncontributory E) Time of day of the seizure

78. Question Two 1) All can be causes of epileptic seizures, except: A) Prenatal complications of pregnancy B) Cerebral infarction C) Brain neoplasm D) Movement disorder E) Hypocalcemia

79. Question Two 1) All can be causes of epileptic seizures, except: A) Prenatal complications of pregnancy B) Cerebral infarction C) Brain neoplasm D) Movement disorder E) Hypocalcemia

80. Question Three 1) Within one of the landmark neurology studies, King et al found that CT scanning caught most brain lesions not detected by MRI scanning, as well as catching more surgically remedial brain lesions. Is this statement true or false: A) True B) False

81. Question Three 1) Within one of the landmark neurology studies, King et al found that CT scanning caught most brain lesions not detected by MRI scanning, as well as catching more surgically remedial brain lesions. Is this statement true or false: A) True B) False

82. End of Lecture Thank you for your attendance. This lecture will be made available at the Internal Medicine Residency website: http://IM.official.ws