eMedicine Specialties > Neurology > Seizures and Epilepsy

Epilepsia Partialis Continua

Author: Claude G Wasterlain, MD, Chair, Department of Neurology, VA Greater Los Angeles Health Care System; Distinguished Professor and Vice-Chair, Department of Neurology, University of California, Los Angeles, David Geffen School of Medicine
Coauthor(s): Leo L Chen, MD, Staff Physician, Department of Neurology, University of California at Los Angeles
Contributor Information and Disclosures

Updated: Jul 15, 2009

Introduction

In 1895, Kojewnikoff described a unique type of prolonged seizure, which he named epilepsia partialis continua (EPC). Since then, this name has been ascribed to various nosological entities: EPC as a variation of jacksonian epilepsy, as a jacksonian status epilepticus, as myoclonus epilepsy, as continuous localized myoclonia, or as an extrapyramidal syndrome.¹

This phenomenon can be considered the status epilepticus equivalent of simple partial motor seizures. It manifests itself as focal motor clonic seizures without jacksonian march; seizures remain localized to the part of the body in which they originate; motor activity is often persistent, lasting for at least 60 minutes and often for hours, days, weeks, or even longer. Consciousness usually is preserved but postictal weakness is frequently evident.^2,3 In the vast majority of cases, the seizures are of cortical origin; however, subcortical mechanisms also have been proposed.⁴ Antiepileptic drugs, with a few notable exceptions, do not seem to significantly alter the course of this condition.⁵ EPC can be an expression of a stable neurological lesion or a progressive disease, such as Rasmussen syndrome.⁶

Historical Perspective

Kojewnikoff⁷ , Bruns⁸ , Olowski⁹ , and Choroschko¹⁰ all reported a similar epileptic condition characterized by intermittent muscular twitching of a body part while consciousness is unaffected. To this condition, Kojewnikoff gave the name of epilepsia partialis continua (EPC). He claimed that its cause might be a tumor, an abscess, syphilis, edema, embolism, or a localized encephalitis. He postulated, without postmortem studies, that the seizures resulted from focal cortical encephalitis.¹¹ This original description of EPC has been discussed by Spiller¹² , Burr¹³ , and others.

During the period 1904-1907, Speilmeyer¹⁴ and Mills¹⁵ reported, under the name of jacksonian epilepsy, cases in which EPC may have been present. Since then, a number of clinical and pathologic studies have further defined the syndrome, its location, and its etiology.¹⁶ In 1966, Juul-Jensen and Denny-Brown⁴ defined, or rather, described, EPC as "clonic muscular twitching repeated at fairly regular short intervals in one part of the body for a period of days or weeks." They also differentiated it from myoclonus by characterizing the latter as "more rapid, lasting less than half a second, involving a variable number of muscles . . . at irregular intervals," but recognized the existence of transition forms, which are difficult to classify.

In 1972, Gastaut defined EPC as a subtype of somatomotor simple partial status epilepticus (SE), which was itself a form of elementary partial status epilepticus; this definition made the point that there are as many types of status epilepticus as there are types of seizures.¹⁷ Several subsequent reviews have used this definition.¹⁸

In 1977, Thomas et al defined EPC as "a partial somatomotor SE...for a minimum of one hour and recurring at intervals of no more than 10 seconds." They carefully described the features of EPC in 32 patients.¹⁶ EPC had a sudden onset in 17 of 25 patients; its duration varied from 4 hours to 18 years. Movement frequency was 0.5-10 Hz, and the duration varied from 25-600 milliseconds, with twitches often recurring every 2-3 seconds. An EEG spike or sharp wave preceded the movement in 9 of 12 patients, and all 5 corticographies revealed a cortical origin. Seventeen of 25 patients had a poor response or no response to anticonvulsants, and 6 of the 7 responders suffered from acute brain lesions; the therapeutic success could have been coincidental. Interestingly, cortical excision failed to stop the seizures in 4 of 5 patients.

In 1985, Obeso defined EPC as spontaneous regular or irregular clonic muscle twitching of cerebral cortical origin, confined to one part of the body and continuing for a period of hours, days, or even weeks.¹⁹ The addition of "irregular" to the description recognizes the fact that the interval between motor twitches can vary but, in the author's view, makes a clear distinction from myoclonus impossible. Cockerell et al in 1996 and Shorvon in 1994 defined EPC as "a syndrome of continuous focal jerking of a body part, . . . occurring over hours, days, or even years" and restricted the definition to jerks of cortical origin; they proposed the name "myoclonica continua" for jerks of subcortical origin.^20,21 While this distinction is attractive in principle, in practice localizing the exact origin of the seizures is often difficult, and clinical activity indistinguishable from EPC has been associated with subcortical pathology (eg, multiple sclerosis).

Wilson and MacBride in 1925¹¹ , Hess and Sethi in 1990²² , and Biraben and Chauvel in 1998 restricted EPC to local and elementary motor signs, regardless of whether it was associated with spreading seizures at times.²³ Indeed, while the localized nature of EPC is one of its most striking features, occasional spread is seen in otherwise typical cases, and using it as an exclusion criterion is not warranted.

Definition

The author defines epilepsia partialis continua as a form of partial status epilepticus with simple motor manifestations that are maintained for over 1 hour, with clonic activity restricted to one body part and recurring at fairly regular intervals. The following modifying factors apply:

• Motor activity often is modified by sensory stimuli.
• Frequency is usually 0.1-6 Hz.
• An occurrence of EPC can continue for long periods of time (sometimes years) without spreading, although spread can occur at times.
• EPC often is associated with postictal or interictal weakness.
• Clinical evolution distinguishes 2 forms (ie, Bancaud type 1, Bancaud type 2): type 1 is usually symptomatic of a focal brain lesion, and the prognosis is the same as that of the associated lesion; type 2 is associated with progressive, idiopathic, neurological deterioration, usually in the form of Rasmussen encephalitis (see Bancaud's classification in Clinical Presentation).

Epidemiology

Since the first description by Kojewnikoff, a number of isolated case reports and small case series have elucidated this syndrome further; unfortunately, however, few epidemiologic studies have been performed. The incidence of EPC is slightly higher in males than in females.^20,4,16 Cockerell et al²⁰ estimated the prevalence of EPC at less than 1 per million, based on 36 cases reported in the United Kingdom over a 1-year period, 10 of the cases being new.

A retrospective review by Sinha observed 76 patients with EPC at a tertiary care center in South India over the course of 14 years. The patient characteristics were as follows: Male-to-female ratio, 46:30; mean age, 30.2+/-23.4 years; and median age, 26 years. About 5-6 cases of EPC were admitted each year in this major referral center that has catered to about 3000-4000 inpatients per year for the past decade.²⁴

Etiology

Clinical and pathologic studies identified various causes of EPC (summarized in Causes below). This long list reflects the diverse nature of the pathological processes that cause focal neocortical seizures. Nothing about these processes is specific, and the unique clinical features of EPC are likely to reflect its anatomical location rather than its etiology. The limbic system, which is involved heavily in processes such as memory and emotion, is designed to spread excitation widely and to modulate excitability of many brain regions; perhaps, as a result of this organization, seizures of limbic origin spread widely and rapidly.

By contrast, neocortex, which is involved in sensory, motor, and cognitive responses, is endowed with powerful lateral inhibition, which probably is designed to keep responses precisely localized. This may be the reason that EPC can go on for a long period of time while remaining precisely localized to a small group of muscles and a small cortical domain. An experimental counterpart of that dichotomy is seen in the different expressions of neocortical versus limbic kindling. Limbic kindling rapidly disseminates seizures across the brain, while seizures induced by neocortex remain localized and spread widely only after gaining access to limbic circuits.

• Cerebral neoplasia
  • Metastasis²⁵
  • Astrocytoma²⁵
  • Oligodendroglioma²⁵
  • Carcinomatosis cerebri²⁵
  • Hemangioma¹⁸
  • Lymphoma¹⁸
  • Meningioma²⁰
• Cortical dysplasias
  • Cortical dysplasia^26,27,28
  • Hemimegalencephaly²³
  • Tuberous sclerosis²³
  • Linear sebaceous nevus syndrome²³
  • Sturge-Weber syndrome²³
• Infectious or parasitic
  • Abscess²⁵
  • Tuberculoma⁴
  • Gumma²⁵
  • Russian spring-summer encephalitis²⁵
  • Subacute measles encephalitis²³
  • Human immunodeficiency virus²⁹
  • Progressive multifocal leukoencephalopathy³⁰
  • Creutzfeldt-Jakob disease²⁰
  • Viral encephalitis or meningo-encephalitis²⁵
  • Cryptococcal meningitis³¹
  • Anti-Hu-associated paraneoplastic encephalitis³²
  • Cysticercosis²⁵
  • Granulomatous diseases²⁵
  • Pertussis infection³³
• Vascular lesions
  • Arteriosclerotic cerebrovascular disease²⁵
  • Embolic or postthrombotic ischemic infarction²⁵
  • Cortical venous thrombosis²⁵
  • Cerebral hemorrhage²⁵
  • Systemic lupus erythematosus²³
  • Sjögren syndrome³⁴
  • Arteriovenous malformation²³
  • Carotid hypoplasia³⁵
• Traumatic lesions
  • Acute head trauma³⁶
  • Posttraumatic cyst²⁵
  • Subdural hematoma²⁵
  • Intracerebral hematoma²⁵
  • Epidural hematoma²⁵
• Drug induced
  • Penicillin²⁵
  • Azlocillin³⁷
  • Cefotaxime³⁷
  • Metrizamide³⁸
• Metabolic
  • Diabetic ketoacidosis³⁹
  • Nonketotic hyperglycemia⁴⁰
  • Hepatic encephalopathy^5,41
  • Uremic encephalopathy⁵
  • Hyponatremia⁵
• Idiopathic
  • Rasmussen chronic encephalitis^23,25
  • Autoimmune
    • Multiple sclerosis⁴²
    • Anti-GluR3 or Anti-NMDA-GluR-Epsilon2 antibodies
  • Genetic
    • Alpers disease
    • Kufs disease⁴³
    • Leigh syndrome and cytochrome C oxidase deficiency⁴⁴
    • Nicotinamide adenine dinucleotide (NADH) coenzyme Q reductase deficiency⁴⁵
    • Mitochondrial cytopathies including mitochondrial encephalopathy with lactic acidosis and stroke (MELAS)⁴⁶

Pathophysiology

Historical studies

In 1885, Kojewnikoff postulated that myoclonus and seizures arose from the cerebral cortex in association with localized encephalitis.⁷ This brilliant insight contrasted with the then current view that somewhat similar clinical entities, such as Friedreich paramyoclonus multiplex and familial progressive myoclonic epilepsy of Unverricht, resulted from hyperexcitability of the anterior horn cells⁴⁷ , and it has been proven right in the overwhelming majority of cases of EPC. In 1922, Souques⁴⁸ considered that dysfunction of the motor cortex was the cause of focal motor seizures but that localized myoclonias must be of subcortical origin. The first EEG study of myoclonus with epilepsy was performed by Grinker et al⁴⁹ in 1938. They demonstrated a temporal correlation between frontal polyspikes and waves and myoclonic jerks in the periphery.

In 1947, Dawson^50,51 showed that the motor jerks were preceded by fast (30 Hz) discharges in the contralateral motor cortex. The EEG discharge had a consistent waveform, beginning with a positive wave immediately followed by a negative shift on which a train of spikes was superimposed. When neither the negative shift nor the spike train occurred, no myoclonic jerking was observed.

Dawson also recorded scalp somatosensory-evoked potentials (SSEP) for the first time in response to electrical stimulation of the nerve trunk. Their maximal amplitude was located near the midline for the lower limb and 6-8 cm lateral to the midline for the upper limb. He concluded that these evoked potentials represented exaggerated responses of the underlying cortex to peripheral stimuli, and that hyperexcitability of motor cortex, rather than increase of afferent volley to the primary somatosensory cortex via subcortical mechanisms, would account for the precentral site of projection.

Kugelberg and Wieden reported a case of EPC and remarked upon the constant relationship, with a 27- to 34-millisecond latency, between myoclonic jerking of the right foot and the focal EEG spikes in the central areas, maximum on the left side near the midline. In this patient, excision of the motor cortex was followed by complete remission of the seizures.⁵²

Physiology

The unequivocal cortical origin of EPC appears to be substantiated in man by clinical, electrophysiological, and neurosurgical evidence. In addition, an epileptogenic lesion of the central cortex can provoke the appearance of this phenomenon in monkeys.⁵³ Since surround inhibition may limit seizure spread more effectively in motor neocortex than in any other area because of the tight afferent-efferent relationships, which support the activation of long-loop reflexes, EPC may be a unique expression of cortical organization.^54,55 However, note that seizures sometimes can be driven from distant or even subcortical sites.⁵⁶

Metabolism

The EPC focus (1) is hypermetabolic as shown by 2-deoxyglucose positron emission tomography (PET); (2) is hyperactive as seen as by magnetoencephalogram (MEG) studies; and (3) shows increased blood flow in single-photon emission computed tomography (SPECT) studies.²³

Synaptic mechanisms

Synaptic mechanisms have been studied only in self-sustaining status epilepticus, not in EPC. The author now suspects that self-sustaining status epilepticus is initiated by failure of GABAergic inhibition but is maintained by widespread potentiation of excitatory (especially N -methyl-D-aspartate [NMDA]) synapses; therefore, established self-sustaining status epilepticus becomes resistant to all agents except NMDA antagonists.⁵⁷ The author could speculate on a similar mechanism in EPC, in which the focus would be characterized by long-term potentiation of glutamate receptors and desensitization of GABA receptors, while GABAergic inhibition would be preserved in the surround.

One patient suffering from a cerebral arteriovenous malformation, who developed EPC of several weeks' duration resistant to phenytoin, carbamazepine, valproate, benzodiazepines, gabapentin, phenobarbital, and primidone, did respond to felbamate, a blocker of NMDA receptors. Further studies will elucidate whether this isolated success was coincidental. Another case of successful treatment with felbamate also has been reported.⁵⁸

Clinical Presentation

Clonic activity can involve any muscle group (see Topographic distribution) and is most common in the upper extremities. Although it is typically invariant and remains localized to a single muscle group in most patients, it may be accompanied by jacksonian spread of the seizure, which may even lead to a complex partial or secondarily generalized seizure. This syndrome also may be accompanied by other neurological and psychopathological symptoms (see Neurological symptoms and Neuropsychological symptoms). Bancaud et al classified EPC into 2 groups (see Bancaud's classification). Both entities start with similar seizures, but type 2 proves to be intractable and progressive. Bancaud divided the clinical course of type 2 into 3 stages, which are as follows:⁵³

• The first stage features only simple partial motor or complex partial seizures, but EPC may occur.
• In the second stage, EPC is seen in the setting of progressive neurological deficit and mental deterioration.
• The third stage is characterized by arrest of deterioration and decrease or disappearance of seizures.

• Head (n=24)
  • Mouth (9)
  • Face (11)
  • Periorbital muscle (2)
  • Soft palate (2)
  • Hypersalivation (1)
• Upper extremities (n=60)
  • Thumb (4)
  • Finger (6)
  • Hand (24)
  • Arm (26)
• Head and upper extremities (n=21)
• Trunk (n=8)
  • Shoulder (4)
  • Breast (1)
  • Abdomen (3)
• Lower extremities (n=22)
  • Big toe (2)
  • Leg (10)
  • Foot (10)
• One side of the body (n=16)

• Motor deficit - 138 (56%)
  • Tetraparesis - 4 (4%)
  • Hemiparesis - 68 (28.3%)
  • Monoparesis - 33 (13.3%)
  • Oculomotor paresis - 2 (0.7%)
  • Facial paresis - 25 (10%)
  • Hypoglossal paresis - 5 (1.9%)
  • Soft-palate paresis - 1 (0.3%)
• Sensory deficit - 52 (21%)
  • Hemihypoesthesia and hemianesthesia - 24 (9.7%)
  • Monohypoethesia and monoanesthesia - 11 (4.4%)
  • Deep sensation – 9 (3.6%)
  • Stereognosis - 8 (3.3%)
• Conjugate deviation of the eyes - 3 (1%)
• Anisocoria - 2 (1%)
• Homonymous hemianopsia - 13 (5%)
• Aphasia - 33 (14%)
  • Motor - 21 (8.8%)
  • Sensory - 6 (2.6%)
  • Amnestic - 6 (2.6%)
• Apraxia - 2 (1%)
• Alexia - 2 (2%)

• Disturbance of consciousness - 21 (36%)
  • Somnolence - 11 (19%)
  • Stupor - 2 (3%)
  • Coma – 8 (14%)
• State of confusion - 9 (15%)
• Disorientation - 6 (10%)
• Labile affect - 3 (5%)
• Stupor - 3 (5%)
• Dementia - 9 (15%)
• Others - 8 (14%)

• Type 1 (classic)
  • Rolandic fixed lesion
  • Neurological deficit
  • Preceding partial motor seizures
  • Following myoclonic jerks
  • Focal abnormalities on EEG
  • Nonprogressive course
  • Surgery usually effective
• Type 2 (Rasmussen)
  • Normal development and history until seizure onset
  • Preceding partial motor seizures
  • Following myoclonic jerks
  • Abnormal EEG background with focal and diffuse paroxysmal abnormalities
  • Progressive course
  • Chronic encephalitis
• Intractable epilepsy

Diagnostic Evaluation

Neurologic evaluation is essential in view of the variety of etiologies and associated illnesses. Magnetic resonance imaging (MRI) can point to the structural lesion of the cortex and/or white matter, and it also can follow the progression of atrophy in Bancaud type 2 EPC.²³ In general, EEG has not been successful in determining the origin of EPC. In Rasmussen encephalitis, the EEG often shows significant lateralized slow-wave activity, and it may give evidence for other seizure types or projected abnormalities suggestive of widespread but lateralized disease. Frequently, lateralized asymmetric background slowing is noted.

Similar findings also can be seen with other etiologies, such as glial tumors. In the case of focal nonprogressive pathologies, such as chronic stroke, the background is rarely as abnormal or asymmetric. This point may help in differentiating a focal nonprogressive pathology from structural diseases with a coexistent metabolic encephalopathy, in which the background is often diffusely abnormal.

Evoked-potential techniques (especially SSEP) have been used to examine the physiological mechanisms and anatomical locations of EPC.⁵ Giant SSEPs are seen often and point to cortical hyperexcitability, which may be an essential mechanism of EPC. PET and SPECT are emerging as useful research tools in the evaluation of the metabolic effects of EPC, especially when CT and MRI findings are normal. PET studies are also likely to enhance understanding of the biochemical and metabolic features associated with the abnormal physiology, and, consequently, they may provide significant information not only for diagnosis but also for treatment of EPC.⁶⁰

Prognosis

The long-term prognosis of EPC depends completely on its underlying cause. The early onset of EPC in a child is often, but not always, a manifestation of neurodegenerative disease or Rasmussen encephalitis, and these conditions often are associated with progressive neurological decline. In cases with adult-onset EPC, the underlying cause can be fixed (eg, cortical dysplasia, stable arteriovenous malformation), self-limiting (eg, trauma, stroke), or progressive (eg, tumor, carcinomatous meningitis); the prognosis depends on the underlying pathology.

Treatment

Treatment should focus on the underlying condition. Antiepileptic drugs (AEDs) must be tried to prevent the spread of EPC but, with a few notable exceptions, are unsuccessful in altering the course of EPC. Phenytoin or phenobarbital may be more effective than carbamazepine or valproate.²³ Echenne reported a case of felbamate success in a patient with hemimegalencephaly and multiple types of seizures that responded poorly to AEDs.⁵⁸

Oral corticosteroid therapy and immunosuppression may be of some benefit in rare cases.²⁵ A correlation has been found between Rasmussen encephalitis and serum antibodies to the glutamate receptor subunits, GluR3⁶³ and NMDA-type GluR-Epsilon2.

Plasma exchange has been reported to have improved EPC significantly. Barrontini et al⁶⁴ reported the use of gamma globulins, but to date few lasting benefits have been reported.

Transcranial magnetic stimulation has been reported to have lasting success in anecdotal cases and seems to deserve further evaluation.^65,66  More recently, Rotenberg has reported patients with EPC who benefited from transient suppression of seizures by undergoing low-frequency transcranial magnetic stimulation.⁶⁷

Nimodipine has been administered successfully in 2 cases of EPC following an acute cerebral event.⁶⁸ Since cytomegalovirus has been implicated in the pathogenesis of Rasmussen syndrome, McLachlan et al⁶⁹ used ganciclovir and reported that EPC was controlled in one patient with this syndrome. Intraventricular interferon alpha was reported to have completely controlled EPC in a patient with Rasmussen encephalitis.

Neurosurgical approaches, such as multiple subpial transections⁷⁰ , may be used as a last resort. Hemispherectomy should be considered in refractory cases of Rasmussen encephalitis. Chronic electrical stimulation was used in 3 patients with EPC, resulting in a decrease in seizure frequency and paroxysmal discharges.

A case of successful treatment of facial myoclonus with botulinum toxin for symptomatic relief from EPC has been reported by Browner.⁷¹

Patient Education

For excellent patient education resources, visit eMedicine's Brain and Nervous System Center. Also, see eMedicine's patient education article Epilepsy.

Keywords

epilepsy, epilepsy treatment, epilepsy symptoms, simple partial status epilepticus, jacksonian status epilepticus, continuous localized myoclonia, somatomotor simple partial status epilepticus, EPC, myoclonus epilepsy

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Guillermo Estrada, MD to the development and writing of this article.

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