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S. Nizam Ahmed, MD, FRCPC; Susan S. Spencer, MD due to brief interruption of blood supply to the brain.
Epilepsy affects approximately 1 percent of the popula- Convulsive movements of the extremities may follow tion and is characterized by recurrent unprovoked some prolonged episodes. Vasovagal syncope may be seizures. A careful clinical history is often helpful in diag- secondary to fear, pain or unpleasant sights such as nosis, classification of seizure and epilepsy types, selection blood or medical procedures. Reflex syncope can fol- of appropriate ancillary studies, selection of anti-epileptic low coughing, micturition, defecation or Valsalva’s drugs, and formulation of a long-term management plan.
maneuver. Other causes, especially in the elderly, in- This article provides directions and guidelines both for clude orthostatic hypotension and cardiac arrhyth- the family practice physician and the specialist in evalu- mias.1 Patients report feeling dizzy/light-headed, full- ating this patient population in the clinics.
ness in ears, nauseous and often gradual graying orblurring of the vision. Patients who fall tend to go down more “gracefully” than those with seizures.
A seizure is defined as an abnormal, excessive, paroxys- Careful history will elicit stereotypical provoking fac- mal discharge of the cerebral neurons. Epilepsy is a tors such as prolonged periods of standing in the heat, chronic condition characterized by recurrent, unpro- sight of blood, micturition, or abruptly assuming an voked seizures. In clinical practice, if a patient has 2 or erect posture after prolonged recumbence. The ab- more seizures, he/she is diagnosed as having epilepsy. sence of an aura (described later), tongue bite, urinary It is of the utmost importance for a clinician to be incontinence and prolonged tonic-clonic activity in the aware of other conditions and/or episodes that may presence of a provoking factor would be more sugges- simulate seizures. In short, the first question to be ad- dressed is: Does the episode in question represent a Transient Ischemic Attacks and Migraines seizure? The following section provides a brief Transient ischemic attacks (TIA) result from a tempo- overview of conditions that can masquerade as seizures.
rary interruption of blood supply in the distribution of a cerebral vessel. It may be secondary to an embolicphenomenon or may result from a critically stenosed A detailed discussion of the differential diagnosis of vessel. “Negative symptoms” such as numbness and seizures and epilepsy is beyond the scope of this article.
weakness are more likely to manifest as compared to Some of the common conditions that present to the the “positive symptoms” (stiffness and twitching) seen epilepsy clinics will be discussed (Table 1).
with seizures. Symptoms appear in a vascular distribu- tion and date back to a few months rather than several A syncope refers to a transient loss of consciousness years. Patients will likely have risk factors for cere-brovascular disease such as hypertension, diabetes Doctor Ahmed is the Director of the Comprehensive Adult Epilepsy and/or coronary artery disease. However, there will be Program at the University of Alberta and an Assistant Professor in certain patients with a diagnostic dilemma and a de- Neurology. He completed his epilepsy fellowship at the Yale tailed work up for TIA and seizures will be warranted.
University School of Medicine and his neurololgy residency at theMedical College of Wisconsin. Doctor Spencer is a Professor of A classic migraine with visual aura, nausea/vomiting Neurology at the Yale School of Medicine and Director of Epilepsy and pounding hemicranial headache can be differenti- Fellowships and Clinical Epilepsy Service. She is a former presi- ated easily from a seizure based on history alone.
dent of the American Epilepsy Society. Please address correspon-dence to S. Nizam Ahmed, MD, FRCPC, 2E3.12, University of However, migraines presenting with isolated symptoms Alberta Hospital, 8440-112 St, Edmonton, Alberta T6G 2B7, such as vertigo, episodic vomiting (cyclic vomiting), vi- Wisconsin Medical Journal 2004 • Volume 103, No. 1
Pseudoseizures and Hysterical Seizures Table 1. Differential Diagnosis of Seizures
Pseudoseizures are paroxysmal attacks of non-epileptic etiology. The clinical attacks may resemble different seizure types and at times are a challenge to the inexpe- rienced. Certain clinical characteristics are suggestive of non-epileptic attacks:2 waxing and waning movements during a single attack, prolonged tonic-clonic activity without postictal disorientation, non-rhythmic pelvic thrusting, non-physiological evolution of symptoms such as motor activity spreading from one hand to the other without first affecting the ipsilateral face or leg. Although several characteristics of pseudoseizures have been described in literature, this is not an easy diag- nosis to make. It is strongly suggested that all such pa- tients should be evaluated by clinicians experienced indealing with epilepsy. A significant number of patientsmisdiagnosed with pseudoseizures may turn out to have Table 2. Classification of Seizures and Epilepsy
epilepsy.3 Inpatient video electroencephalogram is one of the most useful tools in clarifying the correct diagnosis.4,5 Partial (seizures with a focal or localized onset) Generalized (Generalized seizures affect both hemispheres si- Some basic understanding of the classification of seizures and epilepsy is essential before more formal guidelines regarding history taking in epilepsy can be presented. Seizures can be classified as partial or gener- Partial seizures originate from a discrete or localized area of the brain, and may or may not spread to other Epilepsy
areas. If a patient maintains awareness during a partial Examples of localization-related epilepsies seizure he/she is diagnosed with simple partial seizures.
If awareness is lost, the event is classified as a complex partial seizure. A simple partial seizure may evolve into a complex partial and/or secondary generalized seizure.
A generalized seizure does not have a focal onset, and awareness is lost immediately. There are several recog- nized kinds of generalized seizures: absence (brief lapse of awareness); the petit mal; grand mal (tonic then clonic activity); the convulsive; myoclonic (sudden mas- * The patient may appear awake but is unable to interact with sive jerk, usually of upper body); atonic (sudden loss of his surroundings in a meaningful way, therefore the term “lossof awareness” rather than “loss of consciousness” is used.
tone); and tonic (brief generalized stiffening). The termepilepsy incorporates the kind(s) of seizures and otherinformation about presentation and electroencephala- sual changes and aphasia with/without headaches can be gram (EEG). It is broadly classified as localization-re- a challenge. It is important to consider migraines in the lated if the seizures have a focal onset, and generalized differential diagnosis of paroxysmal episodes. A detailed when they begin all over at once. The term idiopathic history of previous attacks, certain triggers (caffeine, denotes that the etiology is unknown, while sympto- sleep withdrawal, chocolate), or family history of mi- matic means that a structural cause has been identified graines may provide additional clues. Empirical treat- and cryptogenic implies that a structural abnormality is ment with antiepileptic/anti-migraine medications may suspected but could not be identified.6 One example is clarify the diagnosis in some instances.
that a 6-year-old, otherwise normal child who presents Wisconsin Medical Journal 2004 • Volume 103, No. 1
with absence seizures (a kind of generalized seizure) What happens during the seizure? Unless a patient would be diagnosed with idiopathic generalized has simple partial seizures with preserved awareness, epilepsy. A 70 year old who presents with focal seizures he/she will not be able to answer this question. A after left middle cerebral artery stroke is said to have lo- witness should be interviewed and specific informa- calization-related epilepsy symptomatic of the stroke. A tion sought that may help classify the seizure patient who is developmentally challenged with gener- type.9,10 Is there head or eye deviation to one side? alized seizures but normal cerebral imaging will be clas- Does the motor activity start on one side of the sified as having cryptogenic generalized epilepsy. body? Is the patient able to talk during the seizure?Is there excessive eye blinking at the onset? If au- tomatisms (defined by Lüders as involuntary, organ- A witness who can supplement the history should ac- ized sequences of movement that are not causally re- company the patient. Collateral history from observers lated to the external environment) occur, are these can also be obtained over the telephone if necessary.
more pronounced on one side? Is there a posturing Ask the patient to describe what happens preceding, of an extremity? Does the patient bite his tongue or during, and following the episode. Let them answer lose control of the bladder function? Seizures origi- this open-ended question in as much detail as they can nating from the frontal eye fields may cause head without interruption. With a good historian, this ques- and eye deviation to the contralateral side. Temporal tion alone may provide all the important details.
lobe seizures are often manifested with lip smacking However, in most instances, further history and details and other oral and alimentary automatic behavior will be required. These questions are presented to the (automatisms), which are most pronounced in the ipsilateral extremity, along with dystonic posturing When did you experience the first seizure in your of the contralateral arm. Occipital lobe seizures can life? The age of onset may shed some light on the present with excessive blinking at the onset, negative classification and etiology of seizures. Seizures start- visual symptoms or visual distortions. Tongue biting ing in the early neonatal period are usually second- and urinary incontinence, although more often seen ary to perinatal insults, metabolic disorders, and with generalized seizures, can also be present in congenital malformation. Generalized seizures tend to present in early childhood or teenage years. A 70 What happens immediately following the seizure? year old who presents with new onset seizures is The immediate period following a seizure is known likely to have structural pathology such as a stroke as the postictal period. Following a generalized or brain tumor. Sometimes a patient cannot answer tonic-clonic seizure (convulsion), the patient may go this question reliably, and it is important to have into a period of postictal sleep. Periods of disorienta- input from a parent or other close family member.
tion and lack of awareness of the surroundings may Do you experience some kind of a warning or un- follow some complex partial seizures. Hemiparesis usual feeling at the onset, or immediately preceding or hemiplegia following a seizure (Todd’s paralysis) the seizure? The warning symptoms that are per- is suggestive of a focal onset. Aphasia with otherwise ceived at the onset of a seizure are called “aura.” normal awareness is suggestive of involvement of the An aura actually represents a simple partial seizure, language areas in the dominant hemisphere. Absence and thus indicates that the seizure is focal in origin.
seizures are typically associated with brief or no pos- A particular aura may help localize a seizure.7,8 Patients with temporal lobe epilepsy may report a Is there a diurnal variation? Certain seizures are déjà vu and/or a rising epigastric sensation, pares- more commonly seen during different times in the thesias may be reported in parietal lobe epilepsy, 24-hour daily cycle. Tonic-clonic and myoclonic and visual distortions or transient blindness may be seizures seen in primary generalized epilepsies are experienced in occipital lobe epilepsy. Generalized more common on awakening or in early morning.
seizures are not preceded by auras since they in- Temporal lobe seizures occur any time. Certain volve the whole brain at onset and there is no frontal lobe seizures have nocturnal presentation, awareness of any component. If auras are reported at the onset of generalized seizures, a focal pathol- Are there any known triggering factors? Seizures ogy should be sought and the generalized classifi- can be precipitated by sleep deprivation, flickering lights, menses, alcohol consumption, medication Wisconsin Medical Journal 2004 • Volume 103, No. 1
Table 3. History of Presesenting Complaints
Past medical history, when combined with seizure semi- ology, can provide useful information in terms of etiol- ogy. In localization-related epilepsy, knowledge of the underlying etiology/pathology can help make useful de- cisions with regard to medical and surgical options. Was the patient the product of a normal full-term Was there any asphyxia or respiratory distress at Injuries related to the seizuresFrequency of visits to the emergency department Were the developmental milestones age-appropriate? Any history of febrile seizures? The risk of devel-oping epilepsy in the presence of simple and com- non-compliance, use of antihistamines, stress, fever, plex febrile seizures is approximately 2% and 13%, or exercise. Identification of a risk factor may help Any history of central nervous system infections What is the seizure frequency? This information is such as meningitis, encephalitis, and Lyme disease? helpful in establishing the response to treatment in In endemic regions, obtain history of known cys- What has been the maximum seizure-free period Any history of head injuries, especially associated since the seizure onset? This question is especially with depressed skull fracture, intracerebral hemor- helpful in trying to determine if any specific rhage, loss of consciousness and prolonged amnesia? antiepileptic drug was more efficacious than the others. Once the maximum seizure-free period is identified, try to determine what medications werebeing used at that time. This medication may be re- Some social aspects directly pertaining to the seizures Is there more than one kind of seizure? Inquire and epilepsy are an important part of the history and about different seizure types, and describe each What is your level of education? In patients with a 10. Has the patient sustained injuries related to the long-standing diagnosis of epilepsy, the level of ed- seizures? This is a very important practical ques- ucation may be a reflection of how well the condi- tion. Patients who are injured either do not have tion has been managed. It also helps to determine auras or do not have enough time after the aura to the level of community support the individual will take preventive measures. The presence of falls in require and the potential of educating the patient to itself does not help classify the seizures, but the in- Are you employed? What is your job description? wearing a helmet and modifying the home environ- Patients whose epilepsy is well-controlled can lead a productive and normal life. Many of these patients 11. What is the frequency of visits to the emergency de- are employed full-time or part-time. If seizures are partment? The answer to this question may shed poorly controlled, getting and maintaining employ- light on the degree of seizure control, as well as the ment may be a challenge.12 The physician can provide comfort level of the caregivers in dealing with this guidance regarding welfare plans and other kinds of condition. Information should be obtained regard- community support. If the patient is employed, the ing the specific situation with each hospital visit, nature of the job should be addressed. A person who such as non-compliance, changes in the medication, is mainly involved with an office job, as a cashier, or and concurrent medical illnesses. If certain precipi- other sedentary tasks may not be at risk. However, if tants are identified, appropriate measures can be you are dealing with a construction worker, heavy taken. If frequent hospital visits result from the equipment mechanic, or someone responsible for su- poor comfort level of the caregivers, proper educa- pervising others in high-risk areas, detailed education tion may help rectify the situation.
with some job modification can be critical.
Wisconsin Medical Journal 2004 • Volume 103, No. 1
Do you drive? Patients with uncontrolled seizures who have altered awareness should not be driving.
Inquire about each antiepileptic drug used at any time, They carry a risk to their personal safety, and en- including strength of tablet, time of intake, duration of danger other civilians. Each province and state has therapy, maximum dose, side effects, and efficacy.
its own driving standards for patients withepilepsy.13 Treating physicians should be familiar with these sets of codes and advise their patients ac- Detailed information should be obtained with regard to cordingly. According to the Wisconsin Department EEGs and neuroimaging such as computed tomogra- of Transportation, to be eligible for a driver’s license, phy (CT) scans of brain and magnetic resonance imag- a person must be episode-free for at least 3 months. Are you sexually active? Do you use contraception?Are you planning pregnancy in the near future? Female patients should be educated about the ter- Information should be obtained about potential side ef- atogenicity of antiepileptic drugs, the lower effi- fects of antiepileptic drugs.16 Excessive drowsiness is cacy of oral contraceptives with enzyme-inducing common with early use of phenobarbital, gabapentin, medication (phenytoin, carbamazepine, and phe- and primidone but can also be seen with carba- nobarbital), and the need for using more than one mazepine, phenytoin, and levetiracetam. Gastrointes- form of contraception. The above information is tinal side effects can be related to any medication but also helpful for patients who are planning preg- are more common with carbamazepine. Weight gain, nancy. Any female patient who is of childbearing hair loss, and postural tremors can be seen with val- age and is or may become sexually active should be proic acid, whereas weight loss and paresthesias are on a daily supplement of folic acid to reduce the more common with topiramate. Blurry vision, risk of neural tube defects in the newborn. Detailed diplopia, and incoordination can be a dose-related side discussion on the issues of pregnancy and epilepsy effect with phenytoin, carbamazepine, and lamotrigine.
Gingival hyperplasia and hirsutism are associated with Do you drink alcohol? Alcohol use is a risk factor for a first generalized tonic-clonic seizure.15Patients with epilepsy should be discouraged from the excessive use of alcohol. This may adversely in- Details about a neurological examination can be found teract with the metabolism of the antiepileptic in any standard book on clinical examination. Here are drugs, or may directly result in seizure exacerba- some key points with regard to patients with epilepsy: tion, especially after continued or binge drinking.
• Look for stigmata of neurocutaneous syndrome such as café au lait spots and iris hamartoms with neurofi- bramatosis, Ash leaf spots, shahgreen patches, subun- Family history is important to determine specific gal fibromas, and adenoma sebaceum with tuberous epilepsy syndromes or other genetically mediated neu- sclerosis, or port-wine stain (capillary hemangioma) rological disorders that have seizures as one manifesta- tion. Examples include juvenile myoclonic epilepsy • Look for asymmetries in the size of limbs or one (JME), familial neonatal convulsions, benign rolandic half of the body (hemiatrophy), which may suggest epilepsy, and the syndrome of generalized tonic clonic seizures with febrile seizures plus. Some of these are • Check for marks or ulcerations on the side of tongue age-limited while others are known to be associated or oral mucous membranes as can be seen with • Gingival hyperplasia can be seen with phenytoin.17 • Dupytrens contractures can be seen with chronic use Precise information should be obtained regarding aller- gies to antiepileptic drugs. Distinction should be made • Dystonic posturing of one arm on stressed gait, such between poorly tolerated gastrointestinal side effects ver- as walking on the sides of the feet may suggest a re- sus a hypersensitivity reaction. If a rash is reported, try to mote insult to the corticospinal tracts.
distinguish between photosensitivity reaction (on sun ex- • Multiple bruises or injuries may result from falls sec- posed regions) versus hypersensitivity (more diffuse).
Wisconsin Medical Journal 2004 • Volume 103, No. 1
Table 4. Common Dose-Related Side Effects of Antiepileptic
Medications
CT scan will help to investigate subdural hematoma, Medication Side
subarachnoid hemorrhage, abscess, neoplastic processes,and other space occupying lesions. CT scan of the brain sedation, headache, blurred vision, ataxia, gastrointestinal(GI) upset is recommended if the history or physical examination is suggestive of a focal pathology. MRI of the brain pro- vides a better resolution of the normal and abnormal structure of the brain. It is recommended to look for pathologies commonly not clarified by the CT scan such as cerebral dysplasia, mesial temporal scleroses or whenhistory and physical examination is suggestive of focal headache, dizziness, insomnia, diplopia, ataxia pathology and the CT does not show the cause. MRI may be requested before the CT for a better resolution.20 fatigue, nausea, abdominal pain, dizziness EEG tests the cerebral function rather than structure.
Epileptiform discharges on the EEG can help classify the seizure types21 and are suggestive of an increased risk of recurrent seizures. Focal and generalized slow- ing is reflective of focal and generalized disturbance of fatigue, confusion, word finding difficulties, cerebral function respectively. Focal disturbance can be seen in strokes, tumors, and abscess. Generalized dis- turbance is seen in toxic, metabolic, or diffuse struc- tural abnormalities. An EEG should be performed in all patients presenting with seizures with the under- confusion, cognitive impairment, including standing that a normal EEG does not rule out a clinical seizure disorder, whereas an abnormal EEG in isolationdoes not confirm the diagnosis of epilepsy.
• End gaze nystagmus with reported diplopia and dif- ficulty in tandem walking may suggest toxicity re- The treatment of seizures and epilepsy is an extensive lated to antiepileptic medications such as carba- topic and beyond the scope of this article. A few gen- mazepine, phenytoin, and lamotrigine.
• A single generalized seizure in the absence of abnor- malities on the physical examination, EEG, and im- A seizure is a symptom of an underlying pathology.
aging studies may not require treatment.22 Investigations are directed at identifying the precipitating • The risks and benefits of treatment versus observa- etiology and conditions that can be arrested, reversed, or tion should be discussed with the patients and tai- treated. A detailed history and physical examination can lored according to each individual case.
provide direction to the extent of investigations. The fol- • Selection of pharmacotherapy should involve con- lowing work up is generally recommended.
sideration of the efficacy, tolerability, side effect pro- file, mechanism of action, and cost.
Hyponatremia, hypoglycemia, hypomagnesimia, ure- • Baseline liver function tests, complete blood count, mia and hepatic encephalopathy can all precipitate seizures. Checking serum electrolytes along with glu- • Potential teratogenic effects should be discussed cose, calcium, magnessium, blood urea nitrogen, creati- nine, and liver function tests may provide useful clues • Interactions with oral contraceptives should be real- to these etiologies. Serum and urine toxicology should be done when substance abuse or drug overdose is sus- • Female patients should be placed on folic acid.
pected. In newborns and young children appropriate • Drug levels should be monitored when compliance Wisconsin Medical Journal 2004 • Volume 103, No. 1
12. Chaplin JE, Wester A, Tomson T. Factors associated with Seizures and epilepsy are classified based on the clinical the employment problems of people with establishedepilepsy. Seizure. 1998;7(4):299-303.
history, physical examination, and ancillary studies, and 13. Hansotia P. Epilepsy and driving regulations in Wisconsin.
treatment decisions follow. Patient education with re- gard to diagnosis, prognosis, and indications for med- 14. O’Brien MD, Gilmour-White S. Epilepsy and pregnancy.
ications is important. In patients with normal intellect, 15. Leone M, Bottacchi E, et al. Alcohol use is a risk factor for a the decision to treat and the choice of antiepileptic drug first generalized tonic-clonic seizure. The ALC.E (Alcohol are mutually agreed on by the patient and the doctor.
and Epilepsy) Study Group. Neurology. 1997;48(3):614-620.
Issues regarding work, driving, pregnancy, and other 16. Buchanan N. The occurrence, management and outcome of antiepileptic drug side effects in 767 patients. Seizure.
limitations should be addressed in detail. If a patient presents with first seizure, ancillary studies such as EEG 17. Perlik F, Kolinova M, Zvarova J, Patzelova V. Phenytoin as a and MRI for localization-related epilepsy should be risk factor in gingival hyperplasia. Ther Drug Monitoring.
1995;17(5):445-448.
arranged. A complete blood count, liver function tests, 18. Mattson RH, Cramer JA, McCutchen CB. Barbiturate-related electrolytes, and renal function tests should be arranged connective tissue disorders. Arch Intern Med. 1989;149(4) before initiating the antiepileptic drugs. 19. Buist NR, Dulac O, et al. Metabolic evaluation of infantile For a patient with newly diagnosed seizures, at least epilepsy: summary recommendations of the Amalfi Group. J one consultation should be obtained from a neurologist Child Neurol. 2002;17(Suppl 3):3S98-102.
to address the need for further investigations and for 20. Adams C, Hwang PA, Gilday DL, Armstrong DC, Becker LE, the choice of antiepileptic medications. The classifica- Hoffman HJ. Comparison of SPECT, EEG, CT, MRI, andpathology in partial epilepsy. Pediatr Neurol. 1992;8(2):97- tion of seizures and epilepsy are critical in decisions 21. Sundaram M, Sadler RM, Young GB, Pillay N. EEG in epilepsy: current perspectives.Can J Neurol Sci.
22. Camfield CS, Camfield PR. Initiating Drug Therapy. In: Bergfeldt L. Differential diagnosis of cardiogenic syncope Wyllie E. ed. The Treatment of Epilepsy; Principles and and seizure disorders. Heart. 2003;89(3):353-358.
Practice. Lippincott Williams & Wilkins. 2001:759-767. Meierkord H, Will B, Fish D, Shorvon S. The clinical features 23. Samren EB, van Duijn CM, Koch S, et al. Maternal use of and prognosis of pseudoseizures diagnosed using video- antiepileptic drugs and the risk of major congenital malfor- EEG telemetry. Neurology. 1991;41(10):1643-1646.
mations: a joint European prospective study of human ter- Kanner AM, Morris HH, Luders H, et al. Supplementary atogenesis associated with maternal epilepsy. Epilepsia.
motor seizures mimicking pseudoseizures: some clinical dif- ferences. Neurology. 1990; 40(9):1404-1407.
24. McKee PJ, Percy-Robb I, Brodie MJ.Therapeutic drug moni- French J. Pseudoseizures in the era of video-electroen- toring improves seizure control and reduces anticonvulsant cephalogram monitoring. Curr Opinion Neurol.
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Holmes GL, Sackellares JC, McKiernan J, Ragland M, 25. Eadie MJ. Therapeutic drug monitoring-antiepileptic drugs.
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So NK. Epileptic Auras. In: Wyllie E. ed. The Treatment ofEpilepsy; Principles and Practice. Lippincott Williams &Wilkins. 2001:299-308. Gupta AK, Jeavons PM, Hughes RC, Covanis A. Aura intemporal lobe epilepsy: clinical and electroencephalographiccorrelation. J Neurol Neurosurg Psychiatry. 1983;46(12):1079-1083.
Serles W, Caramanos Z, Lindinger G, Pataraia E, Baumgart-ner C. Combining ictal surface-electroencephalography andseizure semiology improves patient lateralization in temporallobe epilepsy. Epilepsia. 2000;41(12):1567-1573.
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Wisconsin Medical Journal 2004 • Volume 103, No. 1
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