Clinical manifestations

Presentation and course

The term “aura continua” typically refers to seizures consisting of subjective feelings without visible motor phenomena. Thus, focal status epilepticus with motor phenomena or any other objective phenomena, such as aphasia, is not included. In the 2017 ILAE Classification of Seizure Types, aura continua is classified as a focal aware seizure type with nonmotor onset (22).

The EEG may reveal a focal ictal discharge on scalp EEG during aura continua, but in many cases there is no clear ictal change. When seen, the ictal change on scalp EEG may be subtle and remains focal, without significant spread (27). Even with intracranial EEG recordings, the ictal activity may be highly localized (94; 29).

From a clinical point of view, aura continua can be classified into four types: (1) somatosensory (ie, dysesthesia phenomena that involve the trunk, head and extremities); (2) aura continua that involve the special senses (ie, visual, auditory, vertiginous, gustatory and olfactory); (3) aura continua with predominantly autonomic symptoms; and (4) aura continua with psychic symptoms (83).

A special subtype in children, the so-called abdominal aura continua (abdominal epilepsy, recurring abdominal pain), has been described (64; 47; 57).

Pain as an epileptic aura (86), and painful epileptic seizures are likewise uncommon but described (97; 99; 68). Direct evidence that long-lasting pain occurs as aura continua (ie, as a special form of focal status epilepticus) is also sparse, but some data support this possibility. In 2005, Seshia and McLachlan report two patients with aura continua consisting of long-lasting pain (nasal pain for 2 years in one case and epigastric pain for 8 years in the other) (67). In both cases, the pain resolved after focal resection of the presumed seizure focus in the temporal lobe (left sided surgery in the case of nasal pain and right temporal resection for glioma in the case of epigastric pain).

Aura continua with elementary visual phenomena have been described by Gastaut, and prolonged complex visual hallucinations are described by Gastaut, and Sowa and Pituck (24; 71). Status epilepticus amauroticus is described by Barry and colleagues, and ictal visual hallucinations with reversible postictal hemianopia with anosognosia are described by Barry and colleagues, and Spatt and Mamoli (02; 72). Hadjikoutis and Sawhney described a case with occipital seizures presenting with bilateral visual loss (28).

Various medical conditions have been associated with epileptic visual hallucinations. Ghosh and colleagues reported a 34-year-old woman who developed simple partial seizures with ictal visual hallucinations and interictal right homonymous hemianopia due to left posterior quadrant seizures (27). These initially occurred 8 days after liver transplant surgery and occurred up to 22 times per day, with persistent interictal amaurosis. These continued for 1 week before EEG testing confirmed the epileptic etiology for her symptoms. The seizures ceased after levetiracetam treatment. In this case the etiology was not clear, as no lesion was seen on MRI, but it may have been related to immunosuppressive therapy. Donat and associates also described two men who developed visual hallucinations and hemianopia due to occipital seizures in the setting of nonketotic hyperglycemia (18). Kataoka and Ueno described a case of persistent headache and ictal palinopsia and polyopia in a 54-year-old woman with occipital lobe seizures (38). In this case as well, the MRI was normal. Gabapentin reduced the patient’s headaches and visual symptoms. Aura continua with visual allesthesia (visual images from one half of the visual field transposed to the other half) was reported in a 57-year-old man with a prior right parietal traumatic brain injury due to a gunshot wound (45). In this unusual case, the patient suffered from seizures during which images from his right visual field were transposed to his left. These symptoms eventually became continuous over an hour and correlated with seizures arising from the right parietal-temporal region on EEG. After treatment with lorazepam, levetiracetam, divalproex sodium, and gabapentin, his seizure frequency improved and he experienced occasional simple partial seizures on discharge from the hospital. Paredes-Aragon and colleagues reported a case of aura continua with visual symptoms in a patient with presumed autoimmune epilepsy related to both NMDA and GAD65 receptor antibodies (53).

Schiffter and Straschill as well as Wieser described aura continua musicalis (65; 88). Wieser’s patient was published under the heading psychomotor status epilepticus because, eventually, the aura continua with musical hallucinations (the patient experienced a song well-known and familiar to her) in "endless repetition" and with stereo-EEG documented restricted epileptiform discharges near Heschl gyrus spread to the ipsilateral mesiobasal limbic structures, accompanied by alteration of consciousness. The beginning of this electrical epileptiform status activity was accompanied by musical hallucinations only. Blanke and colleagues describe a patient with epilepsy (secondary to left parieto-temporal brain damage) suffering from the paroxysmal unilateral experience of hearing a person in her near-extrapersonal space associated with a deficit in spatial auditory perception and other paroxysmal disorders of somatognosia (06).

Mesial temporal limbic status with olfactory symptoms has been documented (89). A "gustatory aura continua" occurred, with left hippocampal continuous ictal activity in the depth EEG (94). It was also associated with subtle higher cognitive deficits detected with a lexical decision task. Seshia and McLachlan report one patient with long-lasting metallic taste for 2 years (a 46-year-old with left temporal seizure origin; symptom abolished after surgery; oligodendroglioma) and another with foul taste for 5 years (a 34-year-old with right temporal seizure origin; symptom abolished after surgery; mesial temporal sclerosis) (67).

Hamasaki and colleagues reported a case of a 42-year-old man with a 12-year history of persistent olfactory auras that resolved after focal resection of the prepiriform cortex and focal amygdala resection, where an ictal discharge was seen on intracranial electrode monitoring (29). As in many other cases of aura, the scalp EEG showed no ictal change.

The main clinical features of autonomic seizures are abdominal sensations, apnea, arrhythmias and bradyarrhythmias, chest pain, cyanosis, erythema, flushing, genital sensations and orgasm, hyperventilation, lacrimation, miosis, mydriasis, or hippus, palpitations, perspiration, pilomotor excitation ("gooseflesh"), tachycardia, urinary urgency and incontinence, and vomiting. Focal seizures with autonomic symptoms as the leading feature are well known (96). Under the category nonconvulsive status epilepticus, Rabending and Fischer describe ictal bradycardia and asystole (59). For reference, though not a series of aura, another study evaluating focal epileptic seizures in 43 patients with refractory epilepsy found that 39% had rhythm and/or repolarization abnormalities on ictal ECG, including atrial fibrillation, supraventricular tachycardia, asystole, and other abnormalities (50). It is unclear how often aura continua causes purely cardiac abnormalities, though it is likely uncommon. Autonomic seizures and autonomic status epilepticus have been best studied in Panayiotopoulus syndrome (51). In this syndrome with good prognosis, seizures start with autonomic symptoms, mainly emesis, while the child is fully conscious. Half of the seizures last longer than 30 minutes, constituting autonomic status epilepticus (52; 40). Although many patients have a relatively benign course, there are rare cases of more severe autonomic status epilepticus, including respiratory arrest requiring intubation (17).

Umbilical sensations in children (82), long-lasting borborygmi, widened pupils, pilomotor phenomena, goose-flesh or periodically shivering, etc. have been described (07; 90; 91; 92; 73). Autonomic phenomena may be associated with overt or subtle behavioral changes such as irritability, fear, panic, and sometimes, existential emptiness or some other form of pathological self-perception. One of Seshia and McLachlan’s patients suffered from epigastric fear for 8 years, which started after surgery (left temporal seizure origin; mesial temporal sclerosis) (67).

A particularly rare ictal or status symptom is aggression (14).

Limbic encephalitis might be associated with autonomic aura continua, and pilomotor status epilepticus has been reported in a case with voltage-gated potassium channel antibody positive non-paraneoplastic limbic encephalitis (95).

Ictal depression and anxiety in temporal lobe epilepsy is far more frequent (85); Henriksen as well as McLachlan and Blume describe a status with fear as the outstanding clinical expression (32; 44). A large amount of literature exists on this topic (70; 77). Ictal laughter (48) is usually associated with hypothalamic pathology, mainly hamartoma, in which gelastic seizures are the hallmark. Di Giacomo and colleagues reported a case of a patient with recurrent aura continua consisting of feeling “anxiety, motor agitation, fear and sensation of not being able to breathe” without overt clinical signs (16). She underwent intracranial EEG monitoring, which revealed that these symptoms were due to seizures arising from the left temporal region (recorded via left foramen oval electrodes). Her seizures were eliminated by left anterior temporal lobectomy.

Kim and colleagues evaluated headache as aura via video-EEG monitoring (39). They found that six (0.8%) of 775 patients with focal epilepsy reported a headache aura. The interval between headache onset and clinical seizure onset ranged from 1 to 35 seconds, with interval between headache onset and first EEG change ranging between -5 to 14 seconds. Four of these patients had right temporal seizures, and two had left sided onset (one temporal, one central). Although headache aura was rare, 30.7% of this same cohort reported a postictal headache, which is typically more commonly reported in epilepsy. However, prolonged ictal headaches, a form of aura continua, may rarely occur. A rare ictal phenomenon is "hemicrania epileptica" (34; 01), which may last longer than 30 minutes and, therefore, can then be labeled as a form of status epilepticus. “Hemicrania epileptica” by the International Headache Society (HIS) is defined as an ictal epileptic headache with “ipsilateral location of headache and ictal EEG paroxysms" (31). Thus, by this definition, it encompasses both short as well as long duration headaches associated with seizures and does not solely refer to conditions consistent with aura continua. In contrast, hemicrania continua is a primary headache disorder that is characterized by a continuous unilateral headache of moderate severity, exacerbations of severe pain, and complete responsiveness to indomethacin. In hemicrania continua, visual auras may precede or accompany the pain exacerbations (58; 10). However, due to the multiple clinical similarities between migraine with visual aura (including some cases of hemicrania continua) and occipital lobe seizures, it is possible that they share similar underlying electrophysiologic mechanisms (11).

Penfield introduced the term "experiential" to describe such mental phenomena and divided the patients’ past experience into illusions and hallucinations, which could be predominantly visual, auditory, or both, or an "unclassified" experience such as a dream, a flashback, or a memory without further description. Lennox referred to three categories of "psychic seizures,” which are (1) dream states, feeling of unreality or illusions; (2) hallucinations; and (3) mild confusion or disorientation, a feeling of strangeness without loss of memory and consciousness. Experiential means that the mental phenomena have a relevance to the patient’s past; Gloor specified that they typically combine elements of perception, memory, and affect (25). A series of patients undergoing evaluation for epilepsy surgery reported that experiential auras were highly associated with a left hemisphere dominant seizure focus, with 11 out of 12 patients in that series having a left temporal seizure focus localization (33). In contrast, the investigators did not find that déjà vu was highly lateralized to one hemisphere versus the other. Mesial temporal lobe seizures may present as anxiety disorders (100). Di Giacomo and colleagues reported a case of a 60-year-old woman who was originally diagnosed with anxiety disorder and psychogenic nonepileptic seizures, but later diagnosed with aura continua with psychic symptoms consisting of “anxiety, motor agitation, fear and sensation of not being able to breathe” during intracranial EEG monitoring (16). This case highlights the multitude of difficulties that may arise in establishing this diagnosis when scalp EEG is negative.

The principal ictal "psychic phenomena" may be listed as follows (21):

Prognosis and complications

Aura continua appears to cause no lasting clinical negative sequelae, likely due to the highly focal nature of ictal activity that occurs in this entity. This contrasts with focal status epilepticus with impaired awareness in which case cognitive and other deficits may occur (76; 23).

Clinical vignette

A 50-year-old man with focal epilepsy presented to our epilepsy center with a history of seizures beginning at the age of 10 years. He had a history of (1) focal motor seizures causing tightening of the left lower extremity, at times spreading to cause whole body stiffening for 5 to 15 seconds; (2) rare focal to bilateral tonic-clonic seizures (only when antiseizure medications were missed or changed); and (3) a continuous feeling of tingling in the left foot for years (consistent with aura continua). His convulsive seizures were completely controlled with antiseizure medication. He underwent video-EEG monitoring, which revealed no ictal change during his focal motor seizures, though the motor manifestations recorded by video were consistent with an epileptic semiology. There was also no ictal pattern seen despite his continuous tingling foot sensation. However, his EEG did reveal rare spikes at Cz in wakefulness. His MRI brain was normal. At that time he had multiple focal motor seizures daily despite treatment trials with carbamazepine, lamotrigine, sodium valproate, and phenobarbital. Further trials of topiramate and levetiracetam were also ineffective in fully controlling his seizures. His seizures became milder after further medication changes, but he continued to experience the focal motor seizures affecting his foot once or twice daily and a continuous feeling of left foot tingling despite treatment with phenytoin and zonisamide. Eventually, his zonisamide was tapered and replaced with lacosamide. This caused complete resolution of his continuous foot tingling and a significant reduction in his focal motor seizures. Initially, after beginning lacosamide 200 mg/day (in addition to phenytoin), he had no seizures of any kind, including the aura continua, for 2 months. Now, at greater than 10 years of additional follow-up, after further increases in lacosamide to 500 mg/day and tapering of the phenytoin, he experiences only rare and very mild focal motor seizures consisting of left foot tightening, or brief auras. Soon after beginning lacosamide, his aura continua resolved completely.

This case illustrates the complexity in confirming an epileptic origin for the aura continua, as there was no ictal change on his EEG during his symptoms of continuous left foot tingling (or even during his focal motor seizures). It also illustrates the longevity of symptoms that can occur in some cases of aura continua. Despite lack of ictal EEG confirmation, his clinical history of discrete focal motor seizures affecting the same foot, as well as rare focal to bilateral tonic-clonic seizures and spikes consistent with a seizure focus affecting his foot region strongly support an epileptic origin for the continuous symptoms as well. In his case, no SPECT or PET imaging was available during or after resolution of his aura continua. In many cases, such ancillary tests may be helpful diagnostically as ictal focal hyperperfusion on SPECT or hypermetabolism on PET could be supportive of the ictal mechanism for the symptoms. In this case, his clinical history was strongly supportive of aura continua, and expensive ancillary confirmatory tests would likely not have altered his medical treatment because he also had focal motor seizures for which he underwent medication changes. Ultimately, the resolution of continuous foot tingling with antiseizure medication changes strongly supported the diagnosis of aura continua.

Biological basis

Aura continua appears to arise due to prolonged, long-lasting epileptic discharges arising from very localized cortical regions and possibly deep nuclei as well. Chronic neocortical stimulation may disrupt epilepsy partials continua, as described by Valentin and colleagues (81). The authors described two patients whose seizure focus in the primary motor cortex precluded resection. They, thus, underwent placement of neurostimulator devices and underwent chronic cortical stimulation via subdural strip electrodes at the seizure focus in this region (previously mapped by intracranial electrode monitoring). Both patients had greater than 90% seizure reduction. In both cases, epilepsy partialis continua returned after battery depletion, but replacement again reduced seizures by greater than 90%.

Subcortical structures are involved in other types of focal seizures and may also be important in aura continua. In another case of epilepsy partials continua, Courtin and colleagues report a case of left faciobrachial myoclonus, which responded to neurostimulation of the sensorimotor part of the globus pallidus internus (13). The authors noted that epileptic activity was recorded within the globus pallidus internus, suggesting potential downward spread of the ictal activity from the motor cortex.

The above data suggest that aura continua may similarly involve both cortical and subcortical processes, and neurostimulation for aura continua has not been reported.

Localization

Theoretically, each part of the cortex, and probably deep nuclei as well (09), can give rise to long-lasting localized epileptiform discharges. According to their functional specialization, the epileptic dysfunction of a localized ganglionic structure of the brain may give rise to "positive" or "negative" symptoms of a particular quality.

The most common localization of sensory seizures that involve the trunk, head, and extremities (somatosensory) as well as the special senses (visual, auditory, vertiginous, gustatory and olfactory) are listed in Table 1 together with some references.

Table 1. Principal Ictal “Psychic Phenomena”

It is not clear whether certain brain regions are more likely to cause the well-circumscribed and long-lasting discharge behavior seen in aura continua. By analogy with epilepsia partialis continua and focal status epilepticus with impaired awareness, it is reasonable to assume that certain brain regions are more likely to cause continuous ictal activity (93). From posttraumatic epilepsy, it is well known that the central and mesiotemporal lobe cortices are more seizure-prone than other cortices, but it is less clear whether region-specific differences exist to limit seizure discharges in time.

Etiology and pathogenesis

Aura continua occurs in many different medical conditions, as noted above. It is often associated with an underlying focal cortical abnormality but may occur in individuals without evidence of focal abnormalities on brain imaging. It has been described in patients with focal lesions, including brain tumors and traumatic brain injury, but has also been described during severe metabolic derangements and in individuals with chronic epilepsy. Any condition causing focal seizures could potentially cause aura continua.

Pathophysiology

The exact pathophysiology of aura continua awaits clarification. The ongoing ictal activity of aura continua reflects the intrinsic epileptogenic properties of a discharging epileptogenic focus that remains well localized. There is no further propagation of the epileptiform discharge and no significant ictal spread over time. A hippocampal epileptic focus causing electrographic focal status epilepticus may be limited to a volume of less than 1 cm in diameter (94; 20). Mechanistically, status epilepticus represents the failure of the natural seizure-suppressing mechanisms responsible for seizure termination (84).

Although a detailed discussion regarding the pathophysiology of status epilepticus is beyond the scope of this article, both cellular and network alterations appear to be involved (09). GABAA, NMDA, and AMPA receptors appear to be involved, along with depletion of inhibitory peptides (12). GABAA receptor-mediated inhibition is reduced in animal models of status epilepticus during status epilepticus (36). This reduced inhibition mediated by GABA receptors may be a basic mechanism underlying the self-sustaining and progressive nature of status epilepticus, including aura continua. Additionally, there are important changes in the intracellular and extracellular ionic environment during seizures, which are likely important in enabling ongoing seizure activity. Although local mechanisms are important, larger scale network activity, such as via recruitment of subcortical regions, may also be important (09).

Specialized imaging and cortical stimulation studies have helped to further refine the localization of specific symptoms of aura. Kovacs and associates reported a case of déjà vu occurring during deep brain stimulation only at specific stimulation parameters (41). SPECT imaging during the stimulated déjà vu showed increased perfusion in the right medial temporal regions. Similarly, Takeda and colleagues found that aura continua consisting of continuous déjà vu correlated with hyperperfusion in the entorhinal cortex in SPECT coregistered with MRI (74). Additionally, Bartolomei and associates found that stimulation of the entorhinal cortex in patients with epilepsy elicited déjà vu more readily than during stimulation of the hippocampus (03). However, their EEG data, which showed increased EEG signal correlation between several medial temporal lobe structures during déjà vu, suggested that déjà vu was likely caused by a transient cooperation between these various structures and not solely due to entorhinal cortex activation.

Epidemiology

The incidence and prevalence of aura continua are unknown, as there are limited data regarding this condition, which is primarily reported via isolated case reports or small case series. It appears to be a relatively rare condition, but it may be underreported and possibly under diagnosed, as many patients and clinicians tend to focus on the treatment of more overt and disabling seizures.

Prevention

Treatment of a patient’s chronic epilepsy may reduce the risk of developing aura continua. However, aura continua may occur in individuals without a clear diagnosis of epilepsy and, thus, may be difficult to diagnose in those cases. Vigilance regarding some of the unusual ictal manifestations that occur in aura continua could lead to earlier identification of auras and aura continua in patients at high risk for seizures. Early identification of auras may lead to antiseizure medication treatment, which could reduce the risk for or mitigate the severity of aura continua.

Differential diagnosis

Confusing conditions

An ongoing continuous or recurrent intermittent epileptic discharge might be suspected, and consequently proven, with EEG and/or response to antiseizure medication treatment in someone with epilepsy with known focal pathology and prolonged aura symptoms that fit well with the localization of the epileptic discharge. However, in the absence of clear-cut EEG findings, aura continua could be difficult to diagnose. Not infrequently, convincing ictal discharges cannot be detected without intracranial recordings. Such techniques, of course, are only justified in the context of surgical epilepsy therapy. Autonomic signs and symptoms occur in focal aware seizures and are frequent in focal with impaired awareness seizures. Prolonged autonomic ictal features can mimic psychiatric, endocrine, cardiac, and gastrointestinal disorders (15). Table 2 lists the most important differential diagnosis of autonomic phenomena.

Autoimmune epilepsy may cause aura continua, as well as other forms of status epilepticus. As noted in a review by Toledano and Pittock, there are several neural-specific autoantibodies targeting both intracellular and plasma membrane antigens that are associated with autoimmune epilepsy (75). Status epilepticus, including nonconvulsive status epilepticus, can occur at presentation. A subacute onset of cryptogenic epilepsy, history of autoimmunity or viral prodrome, psychiatric or cognitive features of limbic encephalitis, or history of tumor are some of the clinical features that may raise suspicion for an autoimmune epilepsy. Furthermore, the opercular syndrome (also known by the eponym Foix-Chavany-Marie), and in particular the anterior (frontal) opercular syndrome, which comprises essentially difficulties in speech and swallowing due to the loss of voluntary control of the oro-facio-linguo-pharyngo-masticatory muscles, can be associated with seizures and even with focal status epilepticus (63; 05). Lingual epilepsia partialis continua with disabling dysarthria due to impairment of the left half of the tongue has been reported by Nayak and colleagues in a patient with suspected Rasmussen encephalitis (49). As noted in a previous section, continuous visual focal status epilepticus was reported in a patient with GAD65-R and NMDA-R autoimmune epilepsy (53). Systemic lupus erythematosus may also cause aura continua (46).

Table 2. Differential Diagnosis of Autonomic Aura Continua

Table 3. Differential Diagnosis of Aura Continua with Psychic Phenomena and Psychic Seizures

Associated and underlying disorders

Aura continua might occur de novo, but in most instances occurs in patients with known focal epilepsies, particularly temporal lobe epilepsy. It may be more common in patients with underlying focal pathology, but due to the scarcity of cases, clear evidence from the literature is unavailable. And it is notable that various medical conditions are associated with aura continua, even in the absence of an underlying focal lesion, as noted in prior sections.

Diagnostic workup

To be certain of the diagnosis of aura continua, two principal requirements must be fulfilled: (1) long-lasting somatosensory, special sensory, visceral, or experiential symptom without visible motor component or impairment in level of consciousness; and (2) seizure activity on the EEG. However, as noted above, ictal EEG is often negative in probable aura continua. Polygraphic recordings, such as electrocardiography, respiration, and electrodermal skin responses are helpful for detecting and quantifying autonomic phenomena, which may sometimes occur. If routine scalp EEG is nondiagnostic, ictal SPECT or PET may aid in the diagnosis. Finally, the prompt response to antiseizure medications might be important for the diagnosis. Because the majority of aura continua phenomena are associated with an underlying structural lesion, a thorough examination of the patient, including neurologic, neuropsychologic examinations, and MRI, PET, or SPECT in the ictal and interictal state may be useful. Long-term video-EEG documentation may also be useful, and, in epilepsy surgery cases, intracranial EEG recording may confirm the diagnosis. Symptom abolition of aura continua after surgery (67) or medication treatment may also support this diagnosis.

Management

Aura continua may respond to various standard antiseizure medications. However, similarly to epilepsy partials continua, aura continua is frequently difficult to treat and may be refractory to multiple medications, as in the case of visual allesthesia reported by Mendez and Chen (45). There are various antiseizure medications, which have been reported to be effective, but there are not sufficient data to guide treatment or suggest that specific medications may be superior to others. Treatment should follow standard antiseizure medication guidelines and is outside the scope of this review. Various medications have been reported to be useful. Treatment goals must take into account the risks of possible adverse medication side effects, which could outweigh potential benefits of treatment. Treatment of any underlying etiology should also be a focus of therapy, as in autoimmune epilepsy (54).

Outcomes

There are limited data regarding outcome in aura continua because case reports and small case series constitute the bulk of the available data. Aura continua is often refractory to multiple antiseizure medications. As noted above, potential risks of treatment must be weighed against the benefits of treating the aura continua symptoms, which could vary in severity. Benzodiazepines and antiseizure medication polytherapy are necessary to completely control aura continua in some cases. Although epilepsy surgery has been reported to be effective in some cases, those individuals also had other types of seizures as well, which were the prime clinical indication for surgery. Oversedation, cognitive side effects, dizziness, and other common side effects of antiseizure medications could occur in such cases. Thus, treatment of aura continua must balance the severity of the symptoms with quality of life.

Special considerations

Pregnancy

Treatment in pregnancy is focused on use of the minimum dose and number of standard antiseizure medication treatment(s) that is effective, with preference given to those antiseizure medications associated with lower risk of fetal malformations, cognitive decline, and other potential adverse effects. Discussion of specific medications and treatment of epilepsy during pregnancy follows standard guidelines and is outside the scope of this article.