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Flashcards in DDx: Seizures Deck (13):

Differential Diagnosis of New-Onset Seizures in Adults

Focal seizures -  in which the patient maintains full awareness are termed focal seizures without dyscognitive features (simple partial seizures), whereas those involving an alteration of consciousness, are classified as focal seizures with dyscognitive features (complex partial seizures).  Absence seizures are characterized by brief periods of staring and unresponsiveness, typically lasting seconds, with an immediate return to normal awareness. Generalized tonic-clonic (grand mal) seizures are characterized by stiffening of the trunk and extremities followed by generalized symmetric jerking.  Myoclonic seizures consist of brief, shock-like muscle jerks without loss of awareness. 

Idiopathic (cryptogenic) seizures

Metabolic abnormalities

Generalized Seizure Disorder




Movement disorders

Sleep disorders

Acute structural lesion-related seizures

CNS infection-related seizures

Chronic lesion-related seizures


Primary Neurologic Disorders

Benign febrile convulsions occur in 2% to 5% of children aged 6 months to 5 years, usually during the first day of a febrile illness (temperature > 100.4°F or 38°C), and in the absence of CNS infection (meningitis or encephalitis).

Idiopathic (cryptogenic) seizures account for two-thirds of new-onset seizures in the general population.

Head Trauma is a common cause of epilepsy, particularly when it occurs perinatally or is associated with a depressed skull fracture or intracerebral or subdural hematoma.

Stroke  affecting the cerebral cortex produces seizures in 5% to 15% of patients and can occur after thrombotic or embolic infarction or intracerebral hemorrhage.  Even without rupturing, vascular malformations may be associated with seizures, presumably as a result of their irritative effects on adjacent brain tissue.

Mass Lesions such as brain tumors or abscesses can present with seizures.  Glioblastomas, astrocytomas, and meningiomas are the most common tumors seizures.

A single brain abscess is usually the result of direct extension from an adjacent tissue infection (eg, otitis media, sinusitis, dental infection).  The 2 most commonly isolated organisms are viridans streptococci and Staphylococcus aureus.  

Meningitis or Encephalitis Bacterial (eg, Haemophilus influenzae or tuberculous), viral (eg, herpes simplex), fungal, or parasitic (eg, cysticercosis) infections can also cause seizures.  Meningitis is almost always associated with fever and meningeal signs. Encephalitis can have an insidious onset but is usually associated with altered mental status; a consideration only for new-onset seizures. CSF examination is always required if CNS infection is considered in the differential diagnosis

Develoipomental Anomalies Cortical dysgenesis and neuronal migration disorders can predispose to epilepsy.


Metabolic abnormalities

Hypocalcemia (4.3 to 9.2 mg/dL), hyponatremia (sodium levels less than 120 mEq/L), hypoglycemia (glucose levels of 20 to 30 mg/dL), Hepatic encephalopathy. Drug overdose: Generalized tonic-clonic seizures are most common, but focal or
multifocal partial seizures can also occur. The drugs most frequently associated with seizures are antidepressants, antipsychotics, cocaine, insulin, isoniazid, lidocaine, and methylxanthines. Drug Withdrawl: especially withdrawal from ethanol or sedative drugs, may be accompanied by one or more generalized tonic–clonic seizures that usually resolve spontaneously.

Dx: Basic laboratory tests typically include serum electrolytes, glucose, calcium, magnesium, complete blood count, renal function tests, liver function tests, and a toxicology screen.  In addition to laboratory screening, ECG should be obtained in patients with loss of consciousness to evaluate for possible underlying arrhythmia.Once metabolic and toxic etiologies are excluded as the cause of seizure, most patients require neuroimaging (eg, brain MRI or CT scan) to evaluate for structural brain abnormalities (eg, tumor, stroke, mesial temporal sclerosis) that may serve as a seizure focus.  Lumbar puncture can be considered after neuroimaging has ruled out a space-occupying lesion, but it is typically reserved for patients with suspected meningitis (eg, fever, headache, nuchal rigidity).

Global cerebral ischemia from cardiac arrest, cardiac arrhythmias, or hypotension.  Global ischemia may also be associated with spontaneous myoclonus, Movement Disorders) or, after consciousness returns, with myoclonus  recipitated by movement (action myoclonus).

Hypertensive encephalopathy may be accompanied by generalized tonic–
clonic or partial seizures.

Eclampsia refers to the occurrence of seizures or coma in a pregnant woman with hypertension, proteinuria, and edema (preeclampsia).


Nonepileptic seizures

Attacks that resemble seizures (nonepileptic seizures or psychogenic seizures) may be manifestations of a psychiatric disturbance such as conversion disorder, somatization disorder, factitious disorder with physical symptoms, or malingering.

There is no postictal confusion or abnormal clinical signs after the attack. The EEG, if recorded during an episode, does not show organized seizure activity, and postictal
slowing does not occur. 


Generalized Seizure

Generalized Tonic–Clonic (Grand mal) Seizures: Consciousness is lost, usually without aura or other warning. 

Tonic phase —The initial manifestations are unconsciousness and tonic contraction of limb muscles for 10 to 30 seconds, producing first flexion and then extension, particularly of the back and neck.

Clonic phase —The tonic phase is followed by a clonic (alternating muscle contraction and relaxation) phase of symmetric limb jerking that persists for an additional 30 to 60 seconds or longer. Ventilatory efforts return immediately after cessation of the tonic phase, and cyanosis clears. The mouth may froth with saliva.
With time, the jerking becomes less frequent, until finally all movements cease and the muscles are flaccid. Sphincteric relaxation or detrusor muscle contraction may produce urinary incontinence.

Recovery —As the patient regains consciousness, there is postictal confusion and often headache. Full orientation commonly takes 10 to 30 minutes or even longer in patients with status epilepticus

Status epilepticus —Status epilepticus is defined arbitrarily by seizure continuing for 5 to 30 minutes without ceasing spontaneously or that recur so frequently that full consciousness is not restored between successive episodes.

Absence (Petit Mal) Seizures are genetically transmitted seizures that always
begin in childhood and rarely persist into adolescence.  The spells are characterized by brief loss of consciousness (for 5-10 seconds) without loss of postural tone. Subtle motor
manifestations, such as eye blinking or a slight head turning, are common. Full orientation is present immediately after seizure cessation.  The spells are characteristically inducible
by hyperventilation. The EEG pattern during a seizure is that of 3-Hz spike-wave activity.

Myoclonic seizures are characterized by sudden, brief, shocklike contractions that may be localized to a few muscles or one or more extremities or may have a more generalized distribution causing falls. Juvenile myoclonic epilepsy is the most common cause, with onset usually in adolescence.

Other Types of Generalized Seizures include tonic seizures (not followed by a clonic
phase), clonic seizures (not preceded by a tonic phase).

Atonic seizures result from loss of postural tone, sometimes after a myoclonic jerk, leading to a fall or drop attack. They are most common in developmental disorders
such as the Lennox-Gastaut syndrome.

Dx: MRI and electrophysiologic studies are performed to identify the epileptogenic zone within the brain.

Two convulsions with an EEG

After a single generalized tonic–clonic seizure, recurrence of one or more seizures can be expected within 3 to 4 years in 30% to 70% of untreated adult patients (see
later section on prognosis).

Tx: Anticonvulsant medication

Lamotrigine would likely be effective for prevention of primary generalized seizures. At this time, it appears to have a lower incidence of inducing birth defects than other anticonvulsants. Frequency of cognitive side effects is low. The patient has infrequent seizures so the gradual titration required for lamotrigine to decrease the risk of rash is unlikely to be a problem.

Valproic acid is effective for all types of primary generalized seizures, but is not recommended as the initial treatment in women of childbearing age because of its potential teratogenicity.

Phenytoin may be effective for primary generalized seizures but also has long-term side effects especially in young people and is also associated with increased risk of birth defects.

Topiramate would likely be effective for this seizure type but may cause cognitive side effects. The incidence of teratogenic side effects of topiramate is uncertain at this time.

Absence attacks of the petit mal variety are treated with sodium valproate or ethosuximide.

Patients with complex partial seizures arising from a single temporal lobe are the most frequent surgical candidates; unilateral anterior temporal lobectomy abolishes
seizures and auras in approximately 50% of these patients and significantly reduces their frequency in another 25%.


Partial (Focal) Seizures

Simple Partial Seizures  begin with motor, sensory, or autonomic phenomena, depending on the cortical region affected. For example, clonic movements of a single muscle group in the face, a limb, or the pharynx may occur and may be self-limited; they may be recurrent or continuous or may spread to involve contiguous regions of the motor cortex (Jacksonian march). During simple partial seizures, consciousness is preserved unless and until the seizure discharge spreads to other areas of the brain, producing tonic–clonic seizures (secondary generalization). 

The aura is the portion of the seizure that precedes loss of consciousness and of which the patient retains some memory. In the postictal state, a focal neurologic deficit such as hemiparesis (Todd paralysis) may persist for 30 minutes to 36 hours and indicates an underlying focal brain lesion.

Complex Partial Seizures, formerly called temporal lobe or psychomotor seizures and sometimes now referred to as focal seizures with dyscognitive features, are partial seizures in which consciousness, responsiveness, or memory is impaired. Episodes may begin with an aura. Epigastric sensations are most common, but affective (fear), psychic (déjà vu), and sensory olfactory hallucinations) symptoms also occur. Consciousness is then impaired. Seizures generally persist for 1 to 3 minutes. The motor manifestations of complex partial seizures are characterized by coordinated involuntary motor activity, termed automatism, which takes the form of orobuccolingual movements in approximately 75% of patients and other facial or neck or hand movements in approximately 50%. Sitting up or standing, fumbling with objects, and bilateral limb movements are less common. Secondary generalization of the seizure may occur.

Tx: Phenytoin, carbamazepine, oxcarbazepine, levetiraceatam, topiramate,
zonisamide, sodium valproate and lamotrigine are appropriate drugs of first choice.



Visual or sensory alterations associated with headache; can be problematic when not accompanied by headache



Bizarre spells of altered or lost consciousness of prolonged duration (10-30 min); frequent pelvic thrusting; lack of response to antiepileptic drugs; only truly distinguishable from epileptic seizures by video-EEG monitoring


Movement disorders

Tics, nonepileptic myoclonus


Sleep disorders

Narcolepsy/cataplexy, sleep myoclonus


Chronic lesion-related seizures

Tumor: slowly growing masses may not cause neurologic deficits or the deficit may go unnoticed because of the gradual onset

Developmental malformation: may not manifest with seizures until adulthood.

Previous brain injury: history of any brain abnormality, especially stroke or head trauma, increases the risk of seizures

A consideration in new-onset and chronic seizures. MRI is always necessary to exclude these diagnoses if partial-onset seizures are present



Prodromal autonomic symptoms or palpitations followed by sudden loss of consciousness with rapid return to normal; clonic or tonic movements during syncope can be identical to generalized seizures


Orthostatic Hypotension

Orthostatic syncope is more common in elderly adults; in those taking vasoactive drugs, diuretics, or alcohol; and in the setting of volume depletion or autonomic failure, such as primary or idiopathic autonomic neuropathy

Hx: Syncope occurs on assuming the upright position. May be caused by hypovolemia, drugs (α-adrenergic blockers), or disorders of the autonomic nervous system (idiopathic hypotension, Shy-Drager syndrome).  Patients commonly have symptoms of dizziness, weakness, and fatigue, both before and after the event.


volume down: D/D/D/H (Diarrhea, dehydration, diuresis, hemorrhage)

ANS dysfunction: DM (autonomic neuropathy)/Parkinsons/Elderly (multiple system atrophy)

Px: Orthostatic hypotension is characterized by an abnormal drop in blood pressure with standing (>20 mm Hg systolic or 10 mm Hg diastolic)

SBP decreases 20

DBP decreases 10

HR increases 10

Dx: IVF (ANS if not corrected)