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Overview

Practice Essentials

Frontal lobe epilepsy is characterized by recurrent seizures arising from the frontal lobes. Frequently, seizure types are focal onset with preserved or impaired awareness, often with progression to bilateral tonic-clonic activity. Status epilepticus may be associated more commonly with frontal lobe seizures than with seizures arising from other areas.

Signs and symptoms

Time of day is an important characteristic for seizures originating in the frontal lobe, as the majority of these seizures occur between the hours of 2 am and noon.^[1] A frontal lobe seizure is often the seizure type most difficult to diagnose as it can be easily mistaken for a parasomnia or nonepileptic event. The following features help to distinguish frontal lobe seizures from nonepileptic events:

Stereotyped semiology
Occurrence during sleep
Brief duration (often < 30 seconds)
Rapid secondary generalization
Prominent motor manifestations
Complex automatisms

Other history findings may vary according to the site of involvement, include the following:

Dominant hemisphere involvement - May be indicated by prominent speech disturbances
Supplementary motor area (SMA) - Typically involves unilateral or asymmetrical, bilateral tonic posturing; may be associated with facial grimacing, vocalization, or speech arrest; seizures are frequently preceded by a somatosensory aura; complex automatisms, such as kicking, laughing, or pelvic thrusting, may be present; responsiveness often preserved
Primary motor cortex - Usually focal motor seizures with clonic or myoclonic movements and preserved awareness; jacksonian spread to adjacent cortical areas may occur, and progression to bilateral tonic-clonic activity is frequent; speech arrest and contralateral adversive or dystonic posturing may be present
Medial frontal, cingulate gyrus, orbitofrontal, or frontopolar regions - Complex behavioral events characterized by motor agitation and gestural automatisms; viscerosensory symptoms and strong emotional feelings often described; motor activity repetitive and may involve pelvic thrusting, pedaling, or thrashing, often accompanied by vocalizations or laughter/crying; seizures often bizarre and may be diagnosed incorrectly as psychogenic
Dorsolateral cortex - Tonic posturing or clonic movements often associated with either contralateral head and eye deviation, or less commonly, ipsilateral head turn
Operculum - Swallowing, salivation, mastication, epigastric aura, fear, and speech arrest often associated with clonic facial movements; gustatory hallucinations also may occur
Nonlocalizable frontal seizures - Rare, manifesting as brief staring spells accompanied by generalized spike/wave on EEG, which may be difficult to distinguish from primarily generalized absence seizures; may present as generalized tonic-clonic seizures without obvious focal onset

Physical examination in focal lobe epilepsy is typically normal but may reveal signs suggestive of syndromes or structural lesions that may be associated with epilepsy, such as the following:

Facial dysmorphisms
Cafe-au-lait spots, hypomelanotic macules, or neurofibromas
Spastic hemiparesis, asymmetric muscle bulk

See Clinical Presentation for more detail.

Diagnosis

For new-onset seizures, blood tests should be performed to rule out a metabolic cause (eg, hypoglycemia). For patients with an established diagnosis of epilepsy, blood testing for complications may include the following:

CBC - Monitor for neutropenia and thrombocytopenia
Liver function tests
Antiseizure medication levels

Brain imaging

MRI is the imaging modality of choice in patients with frontal lobe seizures
Underlying lesions are reported to be present in up to 50% of patients with frontal lobe epilepsy
Optimally, MRI should be obtained with high resolution, 1 mm thick slices, and multiple sequences; if EEG or other testing indicates a potential epileptogenic zone, thin slices through the area of interest should be requested
A field strength of 3 Tesla (3T) can further increase the identification of lesions^[2]
PET scanning is often utilized in the presurgical evaluation of patients with extratemporal epilepsy.
On PET scans, interictal hypometabolism, reflective of focal dysfunction, may be seen in areas that were normal on MRI
SPECT scans may be obtained during prolonged video-EEG monitoring; hyperperfusion on ictal SPECT scanning suggests an area of seizure onset

Electroencephalography

Indicated for all patients with frontal lobe epilepsy
Patients with intractable epilepsy, or in whom the diagnosis is doubtful, should undergo prolonged video-EEG monitoring
If the events are primarily or exclusively nocturnal, polysomnography should be considered, with extended EEG montages if available
Interictal EEGs may be normal
On interictal EEG, spikes or sharp waves may be absent; may appear maximal unilaterally (frontal or frontopolar), bilaterally, or in the midline (vertex); or may appear generalized due to secondary bilateral synchrony; background rhythm abnormalities, with or without focal slowing, may be present and depend on the presence of a structural brain lesion
Ictal onset often is seen poorly from the scalp and is highly variable in appearance
Postictal slowing can be confirmatory, and at times, localizing or lateralizing
Patients with suspected frontal lobe epilepsy frequently require invasive EEG monitoring
On intracranial EEG, Ictal onset most often appears as a low-voltage, high-frequency discharge (ie, buzz), although rhythmic activity at alpha, theta, or delta frequencies may be seen

See Workup for more detail.

Management

Antiseizure therapy should be initiated once the diagnosis of epilepsy is established. Many nocturnal seizures with prominent motor manifestations respond extremely well to carbamazepine. Monotherapy is desirable, but some patients require polytherapy.

Patients with medically intractable epilepsy should be considered for resective epilepsy surgery. Other treatment options include the following:

Dietary therapy or ketogenic diet or modified Atkins diet
Responsive neurostimulation (RNS)
Vagal nerve stimulator (VNS)
Corpus callosotomy
Multiple subpial transections

See Treatment and Medication for more detail.

Background

Frontal lobe epilepsy is characterized by recurrent seizures arising from the frontal lobes. Frequently, seizure types are focal onset with preserved or impaired awareness, often with progression to bilateral tonic-clonic activity. Clinical manifestations tend to reflect the specific area of seizure onset and range from behavioral to motor or tonic/postural changes. Status epilepticus may be associated more commonly with frontal lobe seizures than with seizures arising from other areas.

Frontal lobe epilepsy frequently overlaps with sleep-related hypermotor epilepsy (SHE; formerly known as nocturnal frontal lobe epilepsy), which is an epilepsy syndrome characterized by the occurrence of sleep-related hyperkinetic seizures with variable duration and complexity. However, SHE can occasionally arise from extrafrontal areas.^[3]

Disease conditions commonly associated with frontal lobe epilepsy are frequently symptomatic, including congenital causes (such as cortical dysgenesis, gliosis, vascular malformations), neoplasms, head trauma, infections, and anoxia.

Owing to advances in genetic analysis, an expanded number of genetically inherited frontal lobe epilepsy syndromes have been described. Many of these syndromes are characterized by autosomal dominant inheritance.

Quality-of-life issues for patients with epilepsy can include the following:

Coping with the social stigma of epilepsy
Living with restrictions
Living with long-term medical therapy

For more information, see Status Epilepticus.

Go to Epilepsy and Seizures for an overview of this topic.

Developmental lesions

With improvements in neuroimagine, cortical dysplasias are increasingly being identified as epileptogenic lesions. This is particularly true for patiens who were initially assumed to be nonlesional. Other common developmental causes of frontal lobe seizures include hamartomas and nodular heterotopias.

Tumors

Reviews indicate that the epileptogenic lesion in approximately one third of patients with refractory frontal lobe seizures is a tumor.

Common tumors causing frontal lobe epilepsy include gangliogliomas, low-grade gliomas, and epidermoid tumors. High-grade tumors more often present with headache or focal deficits, but many are associated with seizures at some time in their course.

Head trauma

Head trauma is a very frequent cause of damage to the frontal lobes. Risk of later epilepsy depends largely on the severity of trauma. The first seizure usually occurs within months, but may not occur for many years.

Pathologic examination of the frontal lobe frequently reveals meningocerebral cicatrix.

Vascular malformations

Three main types are recognized: arteriovenous malformations, cavernous angiomas, and venous angiomas. Arteriovenous malformations and cavernous angiomas are more likely to cause seizures than are venous angiomas.

Gliosis

Gliosis is identified in many pathologic specimens following surgical resection for frontal lobe epilepsy. It may follow head trauma, neonatal anoxia, or previous resection; often, no cause is identified.

Encephalitis

Although encephalitis commonly produces temporal lobe epilepsy, frontal lobe seizures may occur.

Inherited frontal lobe epilepsy

The seizures of autosomal dominant sleep-related hypermotor epilepsy (SHE)(formerly known as ADNFLE for autosomal dominant nocturnal frontal lobe epilepsy), which are mostly originating in the frontal lobe, are clinically characterized by brief, nocturnal motor seizures that often occur in clusters, mainly during non-REM sleep. Seizures may also occur during daytime naps. Some patients may describe a brief aura, which is typically followed by hyperkinetic or tonic activity. Awareness is often preserved, and daytime seizures are rare. Seizure onset is typically in childhood, but can range from infancy to adulthood. Affected patients have normal neurologic exams and intellect. These seizures typically respond well to carbamazepine (often low doses) and are lifelong, though not progressive. Differentiation from parasomnias remains a challenge.

Autosomal dominant SHE was the first partial epilepsy identified as a single gene disorder. Mutations in 3 nicotinic acetylcholine receptor genes (nAChR alpha-2, alpha-4 and beta-2 subunits) have been associated with this epilepsy syndrome.^[4]Additional causative mutations in the following genes were later identified: CRH, DEPDC5, KCNT1. Penetrance is 70%, and there can be significantly clinical heterogeneity among affected individuals in the same family. The KCNT1 pathogenic variant has been associated with a more severe phenotype.^[5]

Epidemiology

The exact incidence of frontal lobe epilepsy is not known. In most centers, however, frontal lobe epilepsy accounts for 20–30% of operative procedures involving intractable epilepsy.

Sex predilection

No significant sex-based frequency difference has been reported for frontal lobe epilepsy in epidemiologic studies. However, a comparison of frontal lobe versus temporal lobe seizures captured during epilepsy monitoring has suggested a male predominance in frontal lobe seizures.^[6]

Age predilection

Symptomatic frontal lobe epilepsy may affect patients of all ages.

In a large series of cases, the mean subject age was 28.5 years, with age of epilepsy onset 9.3 years for left frontal epilepsy and 11.1 years for right frontal epilepsy.

Morbidity

Complications of frontal lobe epilepsy may include status epilepticus or a comorbid psychiatric or behavioral disturbance.

Status epilepticus is reported in up to 25% of patients with frontal lobe epilepsy. The episodes may be convulsive, nonconvulsive, or focal without impaired awareness.

As with all epilepsy patients, particularly those with medically intractable seizures, patients with frontal lobe epilepsy should be counseled on the risk of SUDEP (sudden unexpected death in epilepsy patients). However, patients with frontal lobe epilepsy do not appear to have a higher incidence of SUDEP compared to other epilepsy populations.^[7]

Prognosis

Approximately 65–75% of patients with frontal lobe seizures respond to appropriate anti-seizure medications and become seizure free. However, approximately 30% of patients will be intractable, many of whom will continue to have frequent nocturnal seizures.

The proportion of patients with medically refractory frontal lobe epilepsy who become seizure free from additional medications or surgical options is lower than in patients with temporal lobe epilepsy.

An important feature in prognosis is the early recognition of frontal lobe seizures as an epileptic syndrome rather than as a parasomnia or a psychiatric condition.

Patient Education

Patient education is important for all patients with epilepsy. Many patients benefit from joining one of the national or regional epilepsy support groups.

Activity restrictions

Patients with epilepsy who are not seizure free have the following restrictions:

Driving - Duration of restriction varies by state
Operating heavy machinery
Activities that involve unprotected heights
Swimming alone

Clinical Presentation

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Tinuper P, Bisulli F, Cross JH, Hesdorffer D, Kahane P, et al. Definition and diagnostic criteria of sleep-related hypermotor epilepsy. Neurology. 2016 May 10. 86 (19):1834-42. [QxMD MEDLINE Link].
Picard F, Bruel D, Servent D, Saba W, Fruchart-Gaillard C, Schöllhorn-Peyronneau MA, et al. Alteration of the in vivo nicotinic receptor density in ADNFLE patients: a PET study. Brain. 2006 Aug. 129 (Pt 8):2047-60. [QxMD MEDLINE Link].
Kurahashi H, Hirose S, Adam MP, Ardinger HH, Pagon RA, Wallace SE, et al. Autosomal Dominant Nocturnal Frontal Lobe Epilepsy. Neurology. 1993. 78(19):1488-92. [QxMD MEDLINE Link].
O'Brien TJ, Mosewich RK, Britton JW, Cascino GD, So EL. History and seizure semiology in distinguishing frontal lobe seizures and temporal lobe seizures. Epilepsy Res. 2008 Dec. 82 (2-3):177-82. [QxMD MEDLINE Link].
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Speck I, Echternach M, Sammler D, Schulze-Bonhage A. Frontal lobe epileptic seizures are accompanied by elevated pitch during verbal communication. Epilepsia. 2018 Mar. 59 (3):e23-e27. [QxMD MEDLINE Link].
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Williamson PD, Spencer DD, Spencer SS, Novelly RA, Mattson RH. Complex partial seizures of frontal lobe origin. Ann Neurol. 1985 Oct. 18 (4):497-504. [QxMD MEDLINE Link].
Laskowitz DT, Sperling MR, French JA, O'Connor MJ. The syndrome of frontal lobe epilepsy: characteristics and surgical management. Neurology. 1995 Apr. 45 (4):780-7. [QxMD MEDLINE Link].
Stefan H, Wu X, Buchfelder M, Rampp S, Kasper B, Hopfengärtner R, et al. MEG in frontal lobe epilepsies: localization and postoperative outcome. Epilepsia. 2011 Dec. 52 (12):2233-8. [QxMD MEDLINE Link].
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Author

Jillian L Rosengard, MD Assistant Professor of Clinical Neurology, Albert Einstein College of Medicine; Attending Physician, Department of Neurology, Montefiore Medical Center

Jillian L Rosengard, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society

Disclosure: Nothing to disclose.

Coauthor(s)

Victor Ferastraoaru, MD Assistant Professor of Neurology, Albert Einstein College of Medicine; Attending Physician, Department of Neurology, Montefiore Medical Center

Victor Ferastraoaru, MD is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, American Epilepsy Society

Disclosure: Nothing to disclose.

Sheryl Haut, MD Professor of Clinical Neurology, Albert Einstein College of Medicine; Director, Adult Epilepsy, Montefiore Medical Center

Sheryl Haut, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, American Clinical Neurophysiology Society, American Epilepsy Society, American Neurological Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Jose E Cavazos, MD, PhD, FAAN, FANA, FACNS, FAES Professor with Tenure, Departments of Neurology, Neuroscience, and Physiology, Assistant Dean for the MD/PhD Program, Program Director of the Clinical Neurophysiology Fellowship, University of Texas School of Medicine at San Antonio

Jose E Cavazos, MD, PhD, FAAN, FANA, FACNS, FAES is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, American Epilepsy Society, American Neurological Association, Society for Neuroscience

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Brain Sentinel, consultant.<br/>Stakeholder (<5%), Co-founder for: Brain Sentinel.

Chief Editor

Selim R Benbadis, MD Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida Morsani College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, American Medical Association

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Bioserenity, Catalyst, Ceribell, Eisai, Jazz, LivaNova, Neurelis, Neuropace, SK Life Science Science, Sunovion, Takeda, UCB<br/>Serve(d) as a speaker or a member of a speakers bureau for: Catalyst, Jazz, LivaNova, Neurelis, SK Life Science, Stratus, UCB<br/>Received research grant from: Cerevel Therapeutics; Ovid Therapeutics; Neuropace; Jazz; SK Life Science, Xenon Pharmaceuticals, UCB, Marinus, Longboard.

Frontal Lobe Epilepsy