Clinical manifestations

Presentation and course

Elementary symptoms are commonly associated with focal seizures with preserved awareness. However, auras can occur before focal seizures with impaired awareness and even generalized seizures (13). Auras can be experienced as negative or, more commonly, positive sensory symptoms. Based on the primary sensory cortex involved, elementary symptoms can be subclassified as follows.

Somatosensory symptoms. Somatosensory symptoms are abnormal sensations experienced as tingling or numbness limited to a well-defined region of the body, which localize the symptomatogenic zone to the contralateral primary sensory cortex. They are unilateral and distal in distribution and exhibit Jacksonian march. Elementary sensory symptoms can be bilateral and more widespread due to activation of the supplementary sensorimotor area or secondary somatosensory area (28). Stimulation of the secondary somatosensory area can also result in unpleasant sensations of heat or pain (32).

Visual symptoms. Commonly, elementary visual symptoms are perceived as stereotyped, multi-colored, and circular flashes appearing on the edge of a temporal hemifield or of both eyes; they multiply in number and size and move horizontally toward the other side. Usually, they develop within seconds and generally last up to 1 to 3 minutes (11). The symptomatogenic zone is identified as the primary visual cortex (Broadmann’s area 17 and 18) without a clear lateralization. Occasionally, lateralization to one visual field may be noted, which localizes the symptomatogenic zone to the contralateral primary visual cortex. Further localization to the upper or lower visual field may also be noted rarely. Not infrequently, patients report amaurosis during or after the ictus (17). As the visual stream projects to associated areas (parieto-temporal cortices through dorsal and ventral streams), more complex visual hallucinations like visual disequilibrium, autoscopy, or nondescribable visual phenomenon may be seen (05).

Auditory symptoms. Elementary sounds and noises in the form of buzzing indicate proximity to the primary auditory cortex in the superior temporal gyrus in the transverse gyrus of Heschl. Elementary auditory auras have poor lateralizing value (15). Auditory symptoms are also seen in a small proportion of patients with mesial temporal lobe epilepsy (03). The presence of auditory auras is a poor prognostic factor for seizure outcomes after anterior temporal lobectomy and amygdalohippocampectomy (04). Ictal deafness has been described from the dominant temporal lobe in the anterolateral part of Heschl’s gyrus (21). Complex auditory phenomena, such as music, relate to auditory association areas in the contiguous temporal neocortex. More complex auditory auras, such as illusions, have been associated with the posterior insula and frontal operculum (36).

Olfactory symptoms. Elementary olfactory hallucinations are usually of sudden onset, lasting 5 to 30 seconds, and may be unpleasant (burnt, chemical, or sickening sensation), neutral, or pleasant (flowers, grilled meat, pistachio); most commonly, they are unpleasant. They are localized to the primary olfactory cortex and have no lateralizing value (34). The anterior olfactory nucleus, piriform cortex, olfactory tubercle, and lateral entorhinal cortex constitute the primary olfactory cortex (26). Tumors in the orbitofrontal region, which is the secondary olfactory cortex responsible for odor discrimination, have been associated with olfactory aura (41).

Gustatory symptoms. Unpleasant taste can be a manifestation of focal seizures. The exact localization is controversial. Cortical stimulation studies have found insulo-opercular regions to be the symptomatogenic zone (19; 32). Gustatory auras have no lateralizing value.

Prognosis and complications

Medical management of elementary aura is not separate from that of focal epilepsy. As aura in focal epilepsy has good localizing value comparable to routine electrophysiological and imaging studies, identifying auras in focal epilepsy is associated with good surgical outcomes in refractory epilepsies. Among the elementary symptoms, the presence of somatosensory, visual, and auditory auras are the most valuable tools in identifying epileptogenic foci. The prognostic value and surgical outcomes of auras were extensively studied in mesial temporal lobe epilepsies. The presence of auditory and vertiginous auras has been associated with a poor seizure outcome after anterior temporal lobectomy and amygdalo-hippocampectomy (04). Moon and colleagues studied the surgical prognostic value of auras in 300 patients who underwent resective surgeries. A total of 225 patients had auras, of which 65 had elementary sensations. The presence of auditory auras was associated with a poor surgical outcome. Inducing habitual auras via intracranial electrical stimulation during presurgical evaluation had no bearing on surgical outcomes (23).

Biological basis

Localization

Elementary somatosensory aura is localized to the contralateral primary sensory cortex and is located in the anterior part of the parietal lobe, which constitutes the postcentral gyrus. Somatosensory auras, which are more widespread or bilateral, are localized to the supplementary sensorimotor area, which is located anteriorly to the primary sensory cortex in the precentral gyrus. The secondary somatosensory area is another localization for widespread somatosensory aura and is located in the superior bank of the Sylvian fissure or the posterior insula. The presence of somatosensory aura in presumed temporal lobe epilepsy raises the question of potential extratemporal seizure onset, which compromises the chances of seizure freedom following standard anterior temporal resection (27).

Elementary visual aura arises from the contralateral primary visual cortex (V1), in close proximity above and below the calcarine fissures. The superior portion of the calcarine fissure corresponds to the inferior visual field, whereas the inferior portion corresponds to the superior field. The primary function of the visual cortex is to process visual information, and it is stratified into six layers: V1 to V5 and the inferior temporal cortex. V1 is the first stop for the visual inputs and, as the visual information is passed along subsequent layers of visual cortex, becomes more specialized. V1 is constituted by simple cells and responds to specific visual cues, such as orientation of edges and lines in a single receptive visual field. V1 through V3 have more complex cells, which respond to edges and orientations of summation of several receptive fields along with movement in specific directions (16). More complex visual hallucinations are localizable to visual association areas and their projections along the dorsal and ventral streams of the visual recognition pathway.

Elementary auditory auras arise from Heschl's gyrus in the superior temporal lobe, which is the primary auditory area involved in auditory processing. Leftward asymmetries in volume of Heschl's gyrus, which is a normal variation in the human adult brain, are due to greater myelination attributed to its specialization for handling fast temporal information (24). On the other hand, the dense, highly interconnected columnar structure in the right auditory cortex makes it effective in fine frequency distinctions (31), thus, the left Heschl's gyrus processes rapidly changing auditory stimuli and the right cortex processes spectrally complex stimuli (40). Also, the processing complexity increases in the superficial layers of Heschl's gyrus (22). Diffusion tensor imaging studies have identified five tracts that pass through Heschl's gyrus fiber intersection area, including the anterior segment of the arcuate fasciculus, middle longitudinal fasciculus, acoustic radiation, inferior fronto-occipital fasciculus, and optic radiation, which are important in higher-order auditory processing, auditory visual association, and auditory learning (12). The affection of some of these fibers results in complex auditory perceptual alterations as seen in frontal opercular epilepsies (36).

Elementary olfactory auras are localized to the anterior olfactory nucleus, piriform cortex, olfactory tubercle, or lateral entorhinal cortex, which are the components of the primary olfactory cortex. Three olfactory areas have been identified in the human brain. The medial olfactory area is the primitive olfactory system located in the midbasal portions of the frontal lobe anterior to the hypothalamus. It connects to the hypothalamus and limbic system and is concerned with basic olfactory reflexes. The lateral olfactory area consists of the prepyriform and pyriform cortex and amygdala and is important in liking healthy foods and disliking unhealthy foods. The newer olfactory area, which is concerned with conscious perception and analysis of olfaction, is connected to the orbitofrontal cortex via the thalamus. The first and second olfactory areas are concerned with elementary olfactory, and the third area with complex auras (34).

Gustatory auras are less well studied and mostly arise from insulo-opercular regions.

Etiology and pathogenesis

The International League Against Epilepsy classified the etiology of seizures and epilepsy syndromes into six categories (13). Etiologies for focal seizures with preserved awareness under these categories include:

Pathophysiology

Epileptogenesis results from the transformation of a normal neuronal network into a chronically hyperexcitable one is a dynamic process that establishes critical interconnections and results in structural changes like neurogenesis, gliosis, axonal damage, sprouting, dendritic plasticity, blood-brain barrier damage, recruitment of inflammatory cells into brain tissue, reorganization of the extracellular matrix, and reorganization of the molecular architecture of individual neuronal cells. Excitatory potentials result in ictogenesis by the generation of paroxysmal depolarization shifts in individual neurons, synchronization of epileptiform discharges, and setting off slow depolarization and burst discharges. The major neurotransmitter involved is glutamate.

Epidemiology

Auras are often underestimated by persons with epilepsy and their doctors unless they progress to motor seizures (08). Though auras are a commonly described phenomenology in focal epilepsies, their occurrence in generalized epilepsies is not uncommon. Auras are reported in around 70% of genetic generalized epilepsies (07). Somatosensory auras occur in 25% to 73% of persons with epilepsy and parietal foci, up to 40% of those with frontal foci, and up to 26% of those with temporal foci (39). Elementary visual auras are the typical manifestation of childhood occipital visual epilepsy, which occurs in approximately 2% to 7% of self-limited focal epilepsies of childhood (09). Auditory aura is a rare symptom seen in around 1.9% of patients with temporal lobe epilepsy overall and is localizable to the temporal neocortex (15). However, it occurs in around 6% to 7% of patients with refractory mesial temporal lobe epilepsy (03). Among persons with focal epilepsies in general, the occurrence of olfactory auras is estimated to be around 5.1% and gustatory auras around 4% (19).

Prevention

There are no specific preventive strategies for focal sensory seizures with elementary symptomatology. Universal seizure precautions to prevent seizure recurrence and reduce the incidence of secondary generalized seizures are the same as in any other seizure type.

Differential diagnosis

Confusing conditions

Migraine with aura. Migraine is a close differential diagnosis of focal sensory seizures with elementary symptoms, the commonest being migraine with visual aura. Migraine and epilepsy often co-exist in the same individual. The prevalence of migraine among persons with epilepsy ranges from 8% to 24% (37) and has been studied extensively in temporal lobe epilepsy and juvenile myoclonic epilepsies (30). The most common type of aura in migraine is visual aura (87.1%), followed by sensory (38.5%) and speech and language auras (15.6%). Olfactory auras are rare in migraine and may be seen in around 3.9% of cases (33; 02). Visual disturbances in migraine aura develop slowly over 4 to 60 minutes and are mainly uncolored or black-and-white patterns, although colorful aura is seen in up to 40% (29). They appear in the center of the visual field and move peripherally. Scintillating scotoma and blurry vision are the most frequent visual symptoms in children, followed by tunnel vision and zig-zag lines. Visual perception abnormalities are seen in adults (18). Migraine aura rarely has accompanying neurologic symptoms like tonic deviation of the eyes and alterations in consciousness. Multiple auras, including somatosensory, auditory, and olfactory hallucinations, can also co-occur in migraine.

Transient ischemic attacks. Transient ischemic attacks are often difficult to differentiate from epileptic auras clinically but are more prolonged (minutes to hours). The phenomenology is mostly negative with a loss of elementary sensory perception like loss of vision or field cuts; positive sensory phenomena are very rare in transient ischemic attack MRI, and EEG might often be normal in both situations.

Psychiatric disorders. Hallucinations have been reported in a variety of psychiatric disorders like schizophrenia, bipolar disorder, severe depression, mania, and substance abuse (10). Seventy percent of patients with schizophrenia experience hallucinations, most commonly auditory but also visual. Auditory hallucinations are typically third-person hallucinations. Visual hallucinations have a predominance of denatured people, body parts, or unidentifiable things. Severe depression is sometimes accompanied by auditory hallucinations, which are usually transient and consistent with the patient's depressed mood. Auditory hallucinations may also occur in mania. Negative hallucinations have been reported in depression.

Associated and underlying disorders

Focal sensory seizures with elementary symptomatology are seen in both self-limited and structural focal epilepsies with foci closer to the primary sensory areas. Evaluation should be directed toward identifying the focus and the underlying structural lesion. Autoimmune and genetic epilepsies may also present with focal sensory seizures with elementary symptomatology.

Diagnostic workup

History and seizure semiology are cornerstones in the diagnosis and localization of an epileptogenic zone. MRI and video-EEG have emerged as the basic investigations in the presurgical evaluation of epilepsy. In presumed MRI-negative epilepsies, functional imaging techniques like PET or ictal SPECT serve as valuable tools. These noninvasive investigations may be supplemented by invasive diagnostic modalities like stereo EEG to decide surgical candidacy and guided resective procedures. fMRI is a noninvasive tool that can help to delineate the epileptogenic zone from the functionally eloquent cortex. Invasive methods such as electrocortical stimulation help guide resection margins preoperatively and intraoperatively (42). When scalp EEG recordings provide no clues regarding the epileptogenic zone, MEG is a complementary tool. EEG is sensitive to radial dipoles, which correspond to top of gyri, whereas MEG is sensitive to tangential dipoles, which correspond to banks of sulci. MEG picks up interictal epileptiform abnormalities that extend no more than 3 to 4 cm² of the activated lateral frontal neocortex and up to 6 cm² of the basal frontal and temporal neocortex, whereas EEG picks up on those discharges that extend greater than 10 cm² of the neocortex (20). The sensitivity of noninvasive modalities in the localization of auras is poor unless it progresses to motor seizure. Hence, invasive recordings and functional imaging modalities are needed for better diagnostic yield.

Management

Management of aura is not independent of seizure per se. Carbamazepine, lamotrigine, oxcarbazepine, and levetiracetam are first-choice medications preferred in focal seizures, with valproate and topiramate being the preferred second choice for monotherapy (06).

Special considerations

Pregnancy

Consideration in pregnant patients is similar to any other patient with focal seizures and includes the risk of teratogenesis from antiseizure medications (38; 35).

Anesthesia

Anesthetic considerations are similar to any other patient with focal seizures and are dependent on underlying etiology.