is it really epilepsy?

see also:

• seizures
• drug-induced seizures
• paediatric seizures
• febrile convulsions in children
• anticonvulsants
• neurology
• syncope / near syncope

• An incorrect diagnosis of a seizure disorder can have many negative consequences for the patient, including expensive and potentially toxic medication regimens, loss of driving privileges, and loss of work.
• Disorders that must be differentiated from epilepsy include migraine, syncope, transient ischemic attack, nonepileptic seizure (psychogenic seizure or pseudoseizure), the episodic dyscontrol syndrome (rage attacks), Meniere's disease, and movement disorders. In children one must also consider breath-holding spells, pallid infantile syncope, tics, night terrors, somnambulism, and the long-QT syndrome.

• “Correct diagnosis of epilepsy is essential to be able to institute appropriate treatment and to establish a long-term prognosis. However, the diagnosis of epilepsy is often difficult. At the onset of the disease, differential diagnosis should be established between an epileptic seizure and a series of paroxysmal phenomena, such as syncope, pseudoseizure, or migraine aura, which may manifest with similar symptoms. It is also important to recognize epileptic seizures caused by acute brain disorders (acute symptomatic seizures) to separate them from spontaneous epileptic seizures (specific to epilepsy).”
• “The circumstances that can complicate early and accurate diagnosis of epilepsy are of a diverse nature. Sometimes, it is the subtle nature of the clinical symptoms of the seizures or their frequent association with other very common conditions that make this diagnosis difficult. In other cases, it is the inadequate or insufficient performance of complementary tests, or the misinterpretation of these tests, which leads to a wrong conclusion. Finally, all too often, it is the obtaining of an insufficiently detailed and precise medical history that lead us to a wrong clinical judgment”

• see also paediatric seizure classification

• simple partial (focal)
  • consciousness is not impaired; motor, sensory, autonomic or psychic symptoms depending on focus.
• complex partial (temporal lobe or psychomotor)
  • consciousness is impaired, automatisms may occur, often a period of post-ictal confusion
• secondarily generalised partial seizures
  • initial partial seizure followed by generalised tonic-clonic seizure with loss of consciousness, increased muscle tone and post-ictal confusion

• absence (petit mal)
• primarily generalised tonic-clonic (GTC) seizure
  • loss of consciousness without warning or is preceded by myoclonic jerks, else similar to secondarily generalised seizure.

• awakening seizures occurring in 1st 2hrs after waking up:
  • usually are primary generalized seizure disorders, including juvenile myoclonic epilepsy, childhood and juvenile absence epilepsies, and GTC seizures on awakening
  • They are idiopathic or hereditary in 84% to 90% of patients
  • usually begin before 15 years of age, and seizure control is common by 25 years of life
• epilepsy commonly occurring during sleep:
  • Partial seizures with secondary generalization
  • other partial seizure disorders such as benign epilepsy with centrotemporal spikes (BECTS) and Landau–Kleffnersyndrome
  • autosomal dominant frontal epilepsy
  • 30% of GTC seizure patients only have sleep seizures
• epilepsy with seizures during the day or night are classed “diffuse”:
  • tend to be associated with an organic etiology,are often refractory to treatment, and have a poor prognosis
  • include Lennox–Gastaut syndrome, West syndrome, and progressive myoclonic epilepsies
  • Partial simple seizure disorders are often diffuse

• onset while the patient is erect
• brief duration (10 seconds)
• flaccid muscle tone during the event
• pale color, cold and clammy skin, or electrocardiographic abnormalities

• onset while the patient is asleep or awake, and in any posture
• duration of one minute or longer
• increased muscle tone during the event
• incontinence, biting of the tongue, flushed color, hot and sweaty skin, stertorous respiration, electroencephalographic abnormalities, or a family history of seizures.
• raised prolactin taken within 20-60min of seizure

• PNES may appear from infancy to adulthood, although their incidence is highest between 15 and 35 years of age.
• more common in women (70%–80%) and, among associated factors, a history of head injury, generally mild, appears in 20% of cases.
• other factors significantly more prevalent in PNES than in epilepsies are personality disorder, perceived childhood neglect, and an excess of adverse life events in the preceding year.
• as a general rule, PNES occur in the presence of witnesses and it is not uncommon for the first seizures to take place in the waiting room.
• they are usually more prolonged than epileptic seizures, which rarely last more than 2 to 3 minutes excluding the postictal period. When they include convulsive motor activity, this activity may be asymmetric and asynchronous, show a varying course over the episode and can be modified by external distraction. Other typical features of pseudoseizures are keeping the eyes closed during the episode, maintaining consciousness during the convulsive phase, the occurrence of weeping, and the absence of incontinence, self-injury, and postictal amnesia.
• VEEG monitoring is a key tool in differential diagnosis of pseudoseizures and has the advantage of allowing careful observation of the semiology of the episodes.
• measurement of serum prolactin levels is useful in patients with suspected PNES.
• serum prolactin often rises to 5 to 10 times normal after generalized tonic-clonic seizures and to 2 to 3 times normal after complex partial seizures.
• peak serum level is obtained from 15 to 20 minutes after the seizure episode and may return to normal after 60 minutes.
• the presence of false-positive (eg. syncope, and, patients with persistent high PRL levels) and false-negative results has caused this test to lose prestige, especially when the seizure shows little motor activity as in complex partial / frontal lobe seizures in which the elevation of prolactin is not significant.
• early diagnosis of PNES is very important for their prognosis and course, and early diagnosis has been shown to be associated with a better outcome.
• treatment is based on providing clear and honest information to the patient and relatives, and support and continuous direct follow-up by the physician treating the patient's epilepsy.

• metabolic causes such as hypoxia, hypoglycaemia
• drug-induced seizures
• drug withdrawal (eg. benzodiazepines, ethanol (alcohol and alcohol withdrawal))
• febrile convulsions in children
• head injury - immediate brief seizure is common and regarded benign; delayed onset may represent subdural or extradural haemorrhage.
• infection - meningitis, encephalitis, HIV / AIDS, cerebral abscesses
• structural causes - brain neoplasms, intracranial haemorrhage, cerebral infact (stroke (CVA)), raised intracranial pressure

• should be performed ASAP in the patient with seizure if either:
  • new focal deficits
  • a persistently altered mental status (with or without intoxication)
  • fever
  • recent trauma
  • persistent headache
  • history of cancer
  • anticoagulant therapy
  • possible acquired immunodeficiency syndrome (HIV / AIDS)
  • children with a postictal focal deficit or altered mental status that does not resolve rapidly
  • should be considered if the patient is over 40 years old or has had a partial seizure

• Seizures often occur as part of an epileptic syndrome
• An epileptic syndrome is a group of signs and symptoms that customarily occur together
• Identification of the syndrome helps determine the appropriate therapy and the prognosis.

• 75% of patients who only have simple or complex seizures have delayed diagnosis and is particularly an issue in children
• simple partial seizures are usually recognized when they have a clear motor component, but they may go unnoticed otherwise.
• seizures that present with symptoms such as déjà vu can be considered a natural phenomenon and, in fact, have been reported in a high percentage of the population. Only the intensity and awareness of the sensation being inappropriate to the situation seem to differentiate the normal experience from the epileptic manifestation.
• it is easy to confuse simple partial seizures with other phenomena, such as the visual alterations in migraine aura, the subtle seizures in the neonate with vagal symptoms, the apneic seizures in the infant with gastroesophageal reflux, or the infantile spasms of an infant with colic.

• autonomic seizures and autonomic status epilepticus typically found in early onset benign childhood occipital epilepsy (Panayiotopoulos syndrome) are often misdiagnosed as encephalitis, syncope, migraine, sleep disorder, or acute gastroenteritis.
• autonomic seizures basically consist of repeated episodes of nausea and vomiting, accompanied by pallor or cyanosis, mydriasis, cardiorespiratory alterations, enuresis, hypersalivation, and modifications of intestinal motility.
  • In one-fifth of seizures, the patient loses consciousness and becomes flaccid. Lateral gaze deviation is typical, and half of autonomic seizures are followed by hemiconvulsion or a generalized clonic seizure.
  • autonomic status epilepticus is said to occur when seizure lasts > 30min which happens in ~50% of cases.
  • The interictal electroencephalogram (EEG) usually shows focal spike-wave activity in any brain region, although with a slight occipital predominance.

• typical absence seizures are not usually diagnosed until their frequency is so high that they cause a reduction in the child's school performance or they are so prolonged that they attract the parents' attention because they are associated with a decreased level of consciousness or other clinical manifestations.

• Both absence and complex partial seizures may be characterized by loss of consciousness, with or without automatic behavior.

• a short duration (10 seconds), a rapid onset without warning, very rapid recovery, or precipitation of the event by hyperventilation;
• a pattern of a spike and a wave at a frequency of 3 Hz on the electroencephalogram provides confirmation.

• duration of one minute or more, an aura, and confusion after the event;
• temporal slowing or sharp waves on the electroencephalogram provide confirmation.

• seizures tend to occur in clusters during sleep and have an atypical or bizarre semiology, and may be easily confused with a hysterical behavior. This may occur when their semiology includes shouting, laughing, cursing, pedaling, clapping, snapping, genital manipulation, pelvic thrusting, running, kicking, and striking.
• these are often misdiagnosed as pseudoseizures.

• the diagnosis of epilepsy is essentially clinical.
• the EEG alone cannot confirm or exclude an epilepsy.
• the EEG helps us to clarify the focal or generalized nature of the seizures and the epileptic syndrome.

• The presence of epileptiform activity on an EEG does not necessarily mean that the patient has epilepsy, because it can be found in approximately 0.5% to 2% of adults and 2% to 4% of healthy children
  • This incidence increases considerably in patients with a history of organic brain damage, in which case we may find epileptiform activity in 10% to 30% of cases.

• The main limitation of EEG studies is that they usually only detect interictal activity because they are not normally done when an epileptic seizure occurs
  • depending on the type of seizure, only 20% to 50% of patients with epilepsy show interictal epileptiform activity on the initial EEG.
  • yield of the recording is considerably higher when it is performed soon, within 24 to 48 hours, after a seizure.
  • With repeated EEGs (and up to 4 may be required), the likelihood of detecting epileptiform activity rises to 80%, a sensitivity similar to that obtained when a sleep EEG is performed after a normal first EEG.
  • it is likely that EEG sleep recordings performed after prior sleep deprivation are more effective for detecting focal and generalized paroxysmal activity than recordings performed during drug-induced sleep.
  • sleep recordings are the only way to diagnose some syndromes such as continuous spike-waves during sleep or the Landau-Kleffner syndrome.
  • The use of routine activation procedures, such as hyperventilation and intermittent photic stimulation, increases the yield of EEG studies, especially in generalized epilepsies.
  • Hyperventilation is usually less useful in adults because of the lower frequency of generalized syndromes such as absence epilepsy. However, it may be an effective procedure to trigger pseudoseizures.
  • simple partial seizures of superficial origin and focal seizures of deep origin may not be accompanied by detectable epileptiform activity.

• According to the ILAE, MRI should be performed in all patients with epilepsy, except when there is an unequivocal diagnosis of benign childhood epilepsy or idiopathic generalized epilepsy, in which it is not expected to find an underlying structural lesion.
• seizures are not controlled with first-line AED.
• seizures recur in a previously controlled epilepsy patient.
• recommended in generalized seizures with onset in the first months of life or in adulthood, given the greater suspicion that a brain lesion may be present in these cases.
• NB. Some common causes of epilepsy, such as cerebrovascular accidents, brain tumors and head injuries, usually lead to emergency hospitalization and are studied by performing a brain computerized tomography.

• the diagnostic yield of MRI performed according to an epilepsy specific protocol is clearly superior to standard MRI for the detection of more difficult lesions.
• In a study of 123 patients undergoing surgery, the sensitivity to detect focal lesions of a standard MRI was 39%, but it rose to 50% when interpretation was done by an expert radiologist and reached 91% when the radiologist performed the MRI with a special protocol for epilepsy.
  • The differences were especially striking in the diagnosis of mesial temporal lobe sclerosis, detected in 7% of patients by a general radiologist in a standard MRI scan versus 45% by an expert radiologist in a special protocol MRI scan.
• up to 40% of neuroimaging studies of epilepsy surgery patients are normal despite the use of an adequate protocol.
  • In these cases, functional neuroimaging tests, such as ictal SPECT or PET, combined with the EEG results, may be helpful to delineate the epileptogenic zone.

• does not necessarily mean it is not epilepsy
  • one-third to one-fourth of patients show true treatment resistance
  • may be because selected Rx is inappropriate for that epilepsy syndrome
    • In a review of patients with idiopathic generalized epilepsies, 71% received contraindicated AEDs.
    • The most common error is the use of voltage-dependent sodium channel blockers (mainly carbamazepine and phenytoin) and GABA inhibitors (vigabatrin, tiagabine, gabapentin), because these drugs may worsen absence seizures and facilitate the occurrence of generalized tonic-clonic seizures.
  • AEDs may unexpectedly aggravate preexisting epileptic seizures or trigger new types of seizures.
    • well-indicated AEDs may have a paradoxical effect, such as the possible aggravation of juvenile myoclonic epilepsy or severe myoclonic epilepsy of infancy (Dravet syndrome) with the use of lamotrigine.
    • Tiagabine may not only cause status epilepticus in generalized epilepsies, but also trigger focal status epilepticus in partial epilepsies.
    • valproate-induced encephalopathy, which may cause encephalopathy and increased number of seizures in focal epilepsies and even more so in generalized epilepsies. This clinical condition may occur without elevation of valproate and ammonium serum levels and in the absence of evident impairment of liver function.
    • induction of negative myoclonus should be considered, which has been reported with the use of the majority of AEDs, including carbamazepine, oxcarbazepine, phenobarbital, phenytoin, valproate, topiramate, lamotrigine, gabapentin, and zonisamide. Negative myoclonus, which is relatively common in the pediatric age, consists on the interruption of tonic muscular activity associated with an epileptiform discharge without evidence of antecedent myoclonia. Its origin is located in the inhibitory premotor cortex and the postcentral cortex, and it is observed in focal epilepsies, especially in rolandic epilepsy.
      • It improves when ethosuximide is added to treatment, which acts by blocking Ca+ channels at the thalamic level.
  • an increased frequency of seizures may be associated with elevated plasma levels of phenytoin and more rarely with the use of carbamazepine, benzodiazepine, or vigabatrin, and exceptionally with other types of AED.

• Unexpected clinical data may sometimes appear during the follow-up of an epileptic patient, which lead us to reconsider the initial diagnosis.
• appearance of triggering factors or onset symptoms more typical of syncope than epileptic seizures makes us suspect that the presumed generalized tonic-clonic seizures we had diagnosed are actually convulsive syncope.
• When a complex partial seizure is followed by syncope-like symptoms, it is important to assess the possible presence of asystole as a complication of the seizure.
• biographical data or family or work conflicts during follow-up of the patient, which, together with a refractory response to treatment, may make us suspect the presence of pseudoseizures.
  • 10% to 40% of patients with confirmed pseudoseizures may coexist true epileptic seizures.

• Diaz et al. Diagnosis of Epilepsy Over the Course of the Disease. The Neurologist. Volume 13(6) Supplement 1, November 2007, pp S11-S19