First epileptic seizure in adulthood

10% of all people experience a seizure once in their lifetime. The exact timing and symptomatic course of the seizure are very important in the workup. There are no laboratory parameters that can prove an epileptic seizure. Cerebral imaging should be performed at the first seizure. It is unclear whether drug treatment should already be given after a first seizure. Studies show that drug therapy after the first epileptic seizure reduces the risk of recurrence in the first two years but does not affect the long-term prognosis of treated patients. After the first seizure, 50% of untreated patients remain seizure-free.

The incidence of epilepsy in Germany is 46/100,000 per year, so that approximately 36,000 new cases can be expected annually. The risk of having a seizure once in a lifetime is about 10% [1], and in the case of a first-time passive disturbance of consciousness, non-epileptic seizure-like events such as dissociative seizures, syncope, etc., must also be considered for differential diagnosis. In practice, three questions usually arise after a first seizure-like event: Was it an epileptic seizure? Does epilepsy exist? And should you treat with medication?

Medical history and physical examination

The self- and external history serves to clarify the exact temporal and symptomatic course before, during and after the seizure-like event. Specific questions to be asked and put into temporal context include prodromal symptoms, aura experience, type and extent of disturbance of consciousness, falls, and sensory, motor, or vegetative symptoms of all body regions. Bloody salivation, tongue biting, enuresis, encopresis, and muscle soreness may be indications of, but do not prove, a generalized tonic-clonic seizure. When taking the personal history, the patient is asked about previous seizure-like events with possibly different or abortive symptoms. Febrile epileptic seizures in childhood with a subsequent symptom-free interval may be indicative of symptomatic epilepsy, as may previous illnesses and medication use.

The physical examination takes place exclusively retrospectively. Inspect for bruises, hematomas and injuries (caution: vertebral body fractures). A mostly lateral tongue bite exists immediately postictally, heals over several days, is painful, and patients remember it very well [2]. Petechial skin hemorrhages – the so-called “trout phenomenon” – result from an increase in pressure in the capillaries during the tonic phase of a generalized seizure [3]. Petechiae are localized to the face, eyelid, neck, and chest and persist postictally for up to three days. They may be the only indication of nocturnal epileptic seizures if they occur recurrently. Dysmorphic signs and skin changes should be noted.

Neurologic status reveals any focal neurologic deficits. If paresis exists immediately after an epileptic seizure, it may be a symptom of cerebral pathology or it may be reversible over minutes to hours in the sense of Todd’s paresis. The differential diagnosis must always include an early attack in the context of a cerebral process, which must be clarified by means of cerebral imaging (CCT/MRI).

Laboratory parameters: Creatine kinase and prolactin

There is no laboratory parameter that proves an epileptic seizure. Serum creatine kinase may be indicative of differential diagnosis. After an epileptic seizure, especially a generalized tonic-clonic seizure, it may increase with a delay of hours to four days [4,5]. Serum controls are recommended after twelve hours at the earliest and in the course of another 24 hours. It should be noted that a sharp increase is often observed in combination with alcohol abuse and can lead to acute renal failure. The increase correlates with the intensity and length of the seizure. A specificity of 86% and a sensitivity of 75% are reported for the discriminability of epileptic seizures, syncope, and nonepileptic dissociative seizures [6].

Prolactin has a circardian rhythmicity with serum peaks around 02:00 to 04:00. 10-30 minutes after an epileptic seizure, the highest concentration is found in the serum, which quickly regresses due to the short half-life of only 32 minutes. Determination is required immediately after a seizure and for baseline determination at least six hours after the event or the following day approximately two hours after awakening. Thus, prolactin concentrations elevated twice above baseline may theoretically help to distinguish tonic-clonic and complex-focal seizures from dissociative seizures [10]. In this context, generalized tonic-clonic seizures are more frequently associated with prolactin increases than complex-focal seizures. On the other hand, elevated prolactin levels can also be detected after syncope, so that a differential diagnosis cannot be made with sufficient certainty [7]. Elevated prolactin levels have also been elevated after dissociative seizures [8,9]. Chen et al. give a sensitivity averaged from seven studies for generalized tonic-clonic seizures of 60% and for complex-focal seizures of 46.1%, while the specificity for both seizure types was 96% [10]. With limited informative value and high requirements for correct determination, this results in only limited clinical relevance.

Laboratory parameters that may provide evidence of symptomatic or acutely symptomatic epileptic seizures include glucose, renal parameters, and especially the electrolytes sodium, calcium, and magnesium. Beghi et al. suggest cut-off values that should be measured within 24 hours of a seizure to be considered indicative of an acutely symptomatic seizure [11].

Cerebral imaging: MRI is superior to CT

Cerebral imaging should always be performed during the first epileptic seizure. Because of its rapid availability, this is often computed tomography. In the course, however, magnetic resonance imaging should always be performed, as this allows better spatial resolution of the brain structures and permits computer-assisted post-processing in the form of morphometric post-processing. The goal is to identify any structural lesion such as hippocampal sclerosis, focal cortical dysplasia, or tumor.

The recommendation for the MRI protocol to be performed includes a T1-weighted 3D volume data set, a transverse FLAIR sequence, a coronary FLAIR sequence, a transverse T2*-weighted sequence, and a coronary T2-weighted sequence. If temporal lobe epilepsy is suspected, look for temporal angulation, i.e., tilt orthogonal to the long axis of the hippocampus. In addition, the entire brain should always be imaged to adequately represent occipital portions as well [12,13].

EEG: as soon as possible after the seizure

A single standard EEG shows epilepsy-type potentials in only 12-27% of patients after an initial seizure [14,15]. This percentage increases slightly if the EEG is done promptly, preferably by 24 hours after the event, and a sleep period can be included [16,17]. A much better statement can be obtained by using a long-term EEG over 72 hours.

Mothersill et al. show that the positive predictive value for the presence of epilepsy when epilepsy-type potentials are detected in the interictal EEG during 72 hours is 98.4% [18]. This allows the conclusion that an unclear seizure event with epilepsy-type potentials in the long-term EEG was epileptic-related in more than 98%. Conversely, without evidence of epilepsy-type potentials within 72 hours, there is only a 1.5% probability that this event was epileptic in origin.

Epilepsy diagnosis: provoked or unprovoked seizure?

When an epileptic seizure is to be diagnosed, a distinction must be made between a provoked occasional seizure (better: acute symptomatic seizure) and an unprovoked seizure. Acutely symptomatic provoked seizures refer to a reversibly reduced “seizure threshold”. They are closely temporally related to brain processes such as intracerebral hemorrhage or ischemia, brain trauma, and cerebral hypoxia (usually within 7 days), but also occur in metabolic disorders such as hyponatremia, hypoglycemia, and uremia [1]. Sleep deprivation as a provoking factor, on the other hand, should be viewed with caution. Lawn et al. show that patients with epileptic seizures after sleep deprivation are more likely to have further seizures than the patient group with clearly acutely symptomatic seizures. Thus, at least mild to moderate sleep deprivation should not be considered a provoking factor, because only a seizure threshold already reduced by another cause favors recurrent seizures due to sleep deprivation [19].

Of course, a first provoked seizure does not allow a diagnosis of chronic epilepsy. According to the well-known 2005 International League Against Epilepsy (ILAE) definition, epilepsy can only be diagnosed after two unprovoked epileptic seizures at least 24 hours apart. However, according to the latest definition of the ILAE, such a diagnosis is possible even after a first unprovoked seizure, if the risk of another seizure in the following ten years is greater than 60% [20]. The limit of 60% is based on the publication by Hauser et al. in which a probability of 73% (confidence interval 59-87%) was determined for the occurrence of a third seizure after two unprovoked seizures [21]. Here, the lower limit of the confidence interval was set by the ILAE as the cut-off value.

In addition, epilepsy can now be diagnosed when a specific epilepsy syndrome is present, e.g., when idiopathic epilepsy is certain following a generalized seizure and matching EEG findings. Risk factors favoring recurrence of seizures include previous brain injury, brain malformations, and abnormal EEG with epilepsy-type potentials. Hesdorffer et al. show that the probability of having a second seizure after a first seizure is 71% after a previous cerebral infarction and 63% after a CNS infection [22]. Thus, the criteria for the diagnosis of epilepsy are met here. However, in other cases, such as focal cortical dysplasias, reliable data are still lacking. If the risk for occurrence of a second seizure is unknown, the ILAE recommends continued use of the old definition (diagnosis of epilepsy only after two unprovoked epileptic seizures at least 24 hours apart).

When to treat?

There is little controversy about the recommendation to begin drug therapy when epilepsy can be diagnosed after a second seizure, when seizure symptoms affect the patient, and when both seizures occurred less than six months apart [23].

In contrast, the decision for or against treatment after the first epileptic seizure is more difficult. Two studies did show that drug therapy after the first epileptic seizure reduced the risk of recurrence in the first two years thereafter [24,25]. However, the long-term prognosis of treated patients versus the prognosis of non-treated patients is not affected. In addition, in one of the two studies, 50% of the non-treated patients remained seizure-free.

Overall, therefore, there is no compelling indication for drug treatment after a first epileptic seizure. Nevertheless, treatment should be advocated if the patient so desires to minimize potential risks, especially if a recurrence risk of at least 60% warrants a diagnosis of epilepsy.

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