Epilepsia Partialis Continua

Article Author:
Zalan Khan
Article Editor:
Pradeep Bollu
Updated:
10/27/2018 12:31:33 PM
PubMed Link:
Epilepsia Partialis Continua

Introduction

Epilepsia partialis continua (EPC) is a rare brain disorder where a patient experiences recurrent and, sometimes, unrelenting focal onset seizures with retained awareness occurring over hours, days, or even years. The pathophysiology of the disease is understood to be complicated. The disease can manifest in a variety of forms such as myoclonic epilepsy, localized myoclonus, Jacksonian epilepsy, and sensorimotor clonic seizures to name a few. Both cortical and subcortical mechanisms have been identified as an etiology. The localized nature of the seizures along with preserved consciousness and postictal confusion and weakness (Todd paralysis) are understood to be characteristic of the disorder but may not be considered pathognomonic due to recorded exceptions. Treatment is centered on a combination of anti-epileptic medications coupled with the identification and resolution of the underlying cause.[1] 

The disorder was first described in 1894 by the legendary Russian neurologist Aleksei Kozhevnikov (1836-1902). The eponym Kozhevnikov epilepsy was coined as a tribute to his work. He postulated that the seizures in EPC were due to a form of focal cortical encephalitis and the subsequent inflammation of cerebral motor fibers. Several years later, in 1958, Rasmussen syndrome (chronic focal encephalitis) was formally described in which patients with the syndrome presented with seizures like that of EPC. Over the years, several neuroscientists have offered different explanations and interpretations for the possible pathophysiological mechanisms.[2]

Etiology

The list of neurological diseases related to epilepsia partialis continua (EPC) is essentially endless, reflecting the diverse nature of the disease. The causes of EPC are very similar to that of any other form of epilepsy as the basic reason for seizures is abnormal electrical activity in the brain brought on by a myriad of pathologies including architectural damage, cortical dysplasia (such as Tuberous Sclerosis, Sturge-Weber syndrome, and linear sebaceous nevus syndrome), drugs, metabolic abnormalities (hyponatremia, hypoglycemia, hyperglycemia, hyperuricemia, uremia), neoplastic process (oligodendroglioma, meningioma, high grade glioma), autoimmune processes (autoimmune encephalitides), or infections. Rasmussen encephalitis or chronic focal encephalitis (CFE), a rare neurological disease seen in children, has shown a strong association with EPC according to the current literature.[3]

Epidemiology

The incidence of epilepsia partialis continua (EPC) is reported to be slightly higher in males compared to females.[4] EPC is a rare disease and has mostly been reported in the form of case reports across the years. Some regional studies, such as the one conducted in the United Kingdom (UK) by Cockerell et al., have reported a prevalence of one per one million over a one-year study period.[5] Similarly, Sinha et al. reported a mean age of 30.2 +/-23.4 in their cohort at a tertiary health care hospital in India for more than 14 years.[6]

Pathophysiology

Kozhevnikov and researchers later examining his work believed the seizures in epilepsia partialis continua (EPC) were cortical in origin and related to some form of localized encephalitis. Hyperexcitability of anterior horn cells was, at the time, believed to be the underlying cause of diseases such as familial progressive myoclonic epilepsy of Unverricht which, like EPC, presented with myoclonic jerks.[7] This thought process was later proven inconclusive after considering subsequent literature. Early studies using electroencephalogram (EEG) and somatosensory evoked potentials (SSEPs) showed that the waveforms associated with EPC had a positive wave followed by negative shifts with a train of superimposed spikes. Hyperexcitability of the motor cortex and consequent exaggerated responses were also understood to play a part in the disease process.[8] Inherent lateral inhibition displayed in the neocortex is understood to keep specific pathway-associated responses precise. This phenomenon may be the reason for the localized nature of seizures seen in EPC compared to seizures arising from allocortex of the limbic pathways which is, by design, meant to spread excitation. Some evidence has also shown Jacksonian spread and secondary generalization of seizures, highlighting the complex pathophysiology of the disease.[9] Studies involving 2-deoxy-D-glucose positron emission tomography (PET) scans, magnetoencephalogram (MEG), and single-photon emission computed tomography (SPECT) have shown that the cortical focus involved EPC is hypermetabolic, hyperactive, and has increased blood flow.[10]

Studies on status epilepticus (SE) have shown a failure of gamma-amino-butyric acid (GABA)-ergic inhibition and consequent unimpeded action of N-methyl-D-aspartate (NMDA) at the synaptic level to play a part in sustaining the epileptic activity. Scientists have postulated a similar process involved in EPC and how it is sustained over extended periods of time, but a causal relationship is yet to be established.[11]Studies have suggested that EPC and its evolution are likely to be related to autoimmune and inflammatory processes involving interleukin 1B and tumor necrosis factor-a. Neuronal cell loss, astrogliosis, and blood-brain barrier damage brought on by these cytokines may contribute to the underlying hyperexcitability of the cortex.[12][13]

History and Physical

A detailed history and neurological examination are warranted due to the extensive myriad of diseases associated with epilepsia partialis continua (EPC). 

Classically, EPC presents as a focal form of status epilepticus (SE) with a preserved consciousness that is restricted to one part of the body, occurring for one hour or more, recurrent, and associated with postictal confusion and weakness. Due to the complex nature of the disease, patients rarely fall into a single diagnostic criterion and, therefore, require a detailed history and physical examination to delineate the nature and possible causes of the seizures.[14]

Neurological deficits are closely related to the nature and degree of severity of the underlying pathology. Motor deficits ranging from quadriparesis to subtle soft palate paresis may be noted. Sensory deficits, similarly, are variable but are less common compared to their motor counterparts. The involvement of the upper extremities is more common. Altered mentation may be seen in patients due to both the associated inter/postictal confusion and the nature/severity of the underlying pathology.[15]

Evaluation

Labs

A baseline laboratory workup may be done during the evaluation of patients with epilepsia partialis continua (EPC) involving tests targeted at probable underlying pathology such as metabolic abnormalities, cerebrovascular, or oncologic conditions.

Imaging

MRI findings can help in delineating structural lesions. Focal cortical dysplasia and Rasmussen encephalitis, two common causes of EPC, are more likely to be identified on MRI because of the advancements in imaging quality and technology in recent years. SPECT scanning may be of use in identifying the epileptic focus, given that the facility and the technically trained staff is available. This imaging modality is mostly used for research and only sparingly in clinical settings. Standard imaging modalities used during neurological workups, such as computed tomography (CT) and MRI scanning, may show no pathology.[16][17]

Electroencephalogram (EEG)

There are no known specific findings on EEG in patients with EPC and can take the form of spikes, sharp waves, and periodic lateralized epileptiform discharges (PLEDs) with slow-wave activity. Sometimes, asymmetrical background slowing is noted. A normal EEG cannot rule out EPC with certainty as the focus of the seizures may be subcortical.[14]

Somatosensory evoked potentials

Somatosensory evoked potentials (SSEPs) have been of some help in localizing the focus of the seizures. Studies using SSEPs have shown hyperexcitability of the motor cortex and the subsequent exaggerated responses to peripheral stimuli.[5][18]

Treatment / Management

The underlying pathological condition leading to epilepsia partialis continua (EPC) is the initial focus of the management strategy. The central aspect of any treatment regimen is seizure control using anti-epileptic medication(AED). Some drugs have been seen to be more effective than others, but polytherapy using multiple AEDs is fairly common. Studies have shown that phenytoin and phenobarbital may be more effective than valproate or carbamazepine. Newer AEDs like levetiracetam, brivaracetam, lacosamide, and zonisamide may also be used as they are well tolerated.[19][20] Therapy with felbamate has also shown positive results, particularly in resistant cases.[21]Rasmussen encephalitis has been seen to be responsive to immunosuppressive agents such as rituximab, tacrolimus, intravenous immunoglobulin (IVIG), and plasma exchange.[22][23][24] Evidence has also shown some efficacy of ganciclovir and intraventricular interferon alfa in extremely small cohorts.[25][26]

Surgical interventions such as hemispherectomy may be considered in cases of Rasmussen encephalitis. Furthermore, newer techniques such as repetitive transcranial stimulation and botulinum toxin have reported some degree of success in specific cases.[27][28][29]

Staging

Bancaud et al. proposed a classification for epilepsia partialis continua (EPC) in 1982 based on findings in a cohort of 23 patients.[29]

Type 1 (Classic)

  • Rolandic fixed lesions
  • Neurological deficit
  • Preceding focal motor seizures
  • The long delay of onset of myoclonic jerks
  • Localized EEG changes
  • The nonprogressive course of the disease
  • Surgical intervention effective

Type 2 (Rasmussen)

Early onset of seizures

  • High frequency of seizures
  • Abnormal EEG pattern with slow spikes (sharp waves) with variable localization
  • Progressive course and associated
  • Neuropsychological symptoms of sleep and behavior
  • Diffuse cerebral lesions
  • Short delay of onset of myoclonic jerks

Furthermore, Bancaud and his team divided type 2 into three stages.

Stage 1. Only focal motor seizures with preserved awareness or loss of awareness

Stage 2. Symptoms of EPC along with progressive neuropsychological deterioration

Stage 3. The arrest of deterioration and decrease in the frequency of seizure or eventual resolution

Prognosis

Prognosis is mostly dependent on the underlying cause of epilepsia partialis continua (EPC). Children with focal encephalitis, such as those with Rasmussen encephalitis or other degenerative pathologies, tend to have a poorer prognosis. Furthermore, children experiencing EPC in the late stages of the disease are more likely to have a lethal outcome.[15]Adult-onset EPC involves reversible underlying causes and tends to have a better prognosis. Aggressive and prompt management is warranted in specific cases due to the propensity of the disease process to worsen or cause permanent structural damage.[30]

Enhancing Healthcare Team Outcomes

Epilepsia partialis continua (EPC) is an unusual manifestation of epilepsy composed of a sustained repetition of focal onset seizure fragments in rapid succession. EPC can range from anywhere between one hour to several years. EPC may occur as a single episode, repetitive episodes, or as a chronic progressive or non-progressive disorder. In some cases, EPC may spread or generalize.

A plethora of etiologies can be local or systemic. Several structural, metabolic and autoimmune disorders may cause EPC, ranging from strokes and hematomas to diseases like Rasmussen encephalitis. The diagnostic workup includes magnetic resonance imaging to clarify the etiology and EEG which typically shows focal epileptiform or slow wave activity but may vary from etiology to etiology. EEG may also be unrevealing and show no abnormal findings.

The symptoms of EPC have been interpreted to be due to cortical hyperexcitability, but the exact pathophysiology is poorly understood due to a high degree of variability. In general terms, EPC seems to represent an oscillation of excitation and inhibition in a feedback loop whose mechanisms are still not fully understood. It seems that EPC only occurs rarely in an otherwise healthy brain.

Treatment options are limited and specific etiologies have to be taken into consideration, but EPC has shown to be resistant to antiepileptic drugs (AEDs). Hemispherectomy may be a treatment choice in patients with Rasmussen encephalitis. The overall evidence is limited and mostly in the form of case series. A detailed neurological evaluation is warranted, coupled with a consultation with a group of specialists including neurologists, neurosurgeons, neurointensivists, and rehabilitation specialists. It is also important to note that patient attendants must be educated about this complicated disease and its management options.