Epilepsia Partialis Continua 

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, with the condition being described as a variation of jacksonian epilepsy, as a jacksonian status epilepticus, as myoclonus epilepsy, as an extrapyramidal syndrome, or as continuous, localized myoclonia.

Epilepsia partialis continua 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, and 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.^{[1, 2]}

In the vast majority of cases, the seizures are of cortical origin; however, subcortical mechanisms also have been proposed.^[3]

EPC can be an expression of a stable neurologic lesion or a progressive disease, such as Rasmussen syndrome.^[4]

Antiepileptic drugs, with a few notable exceptions, do not seem to significantly alter the course of this condition.^[5]

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.

Go to Epilepsy and Seizures, Status Epilepticus, and Partial Epilepsies for an overview of these topics.

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 1 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

Clonic activity in EPC can involve any muscle group 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.

Bancaud’s classification

Bancaud et al classified EPC into 2 groups. 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.^[6] 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 neurologic deficit and mental deterioration. The third stage is characterized by arrest of deterioration and decrease or disappearance of seizures.

Type 1 (classic) is characterized by the following^[7] :

• Rolandic fixed lesion
• Neurologic deficit
• Preceding partial motor seizures
• Following myoclonic jerks
• Focal abnormalities on electroencephalogram (EEG)
• Nonprogressive course
• Surgery usually effective

Type 2 (Rasmussen) is characterized by the following:

• Normal development and history until seizure onset
• Preceding partial motor seizures
• Following myoclonic jerks
• Abnormal electroencephalographic background, with focal and diffuse paroxysmal abnormalities
• Progressive course
• Chronic encephalitis

Intractable epilepsy is the third classification.

Patient education

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Since the first description by Kojewnikoff, a number of isolated case reports and small case series have elucidated this syndrome further. However, few epidemiologic studies have been performed.

Cockerell et al^[8] 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.

The incidence of EPC is slightly higher in males than in females.^{[3, 9, 8]}

In a retrospective review by Sinha and Satishchandra of 76 patients with EPC at a tertiary care center in South India over the course of 14 years, the investigators found the following^[10] :

• Male-to-female ratio, 46:30
• Mean age, 30.2+/-23.4 years
• Median age, 26 years

The unequivocal cortical origin of EPC appears to be substantiated in humans by clinical, electrophysiologic, and neurosurgical evidence. In addition, an epileptogenic lesion of the central cortex can provoke the appearance of this phenomenon in monkeys.^[6] 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.^{[11, 12]} However, note that seizures sometimes can be driven from distant, or even subcortical, sites.^[13]

Metabolism

The EPC focus (1) is hypermetabolic, as shown by 2-deoxyglucose positron emission tomography (PET) scanning; (2) is hyperactive, as seen as by magnetoencephalogram (MEG) studies; and (3) shows increased blood flow in single-photon emission computed tomography (SPECT) scan studies.^[14]

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.^[15]

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.

EPC seizures of the neocortex versus non-EPC seizures of the limbic system

The limbic system, which is involved heavily in processes such as memory and emotion, is designed to spread excitation widely and to modulate excitability in 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.

Causes of EPC

Clinical and pathologic studies have identified various causes of epilepsia partialis continua (EPC). This long list reflects the diverse nature of the pathologic processes that cause focal neocortical seizures. Nothing about these processes is specific, and the unique clinical features of EPC are likely to reflect its anatomic location rather than its etiology.

Causes of EPC associated with cerebral neoplasia include the following:

• Metastasis^[16]
• Astrocytoma^[16]
• Oligodendroglioma^[16]
• Carcinomatosis cerebri^[16]
• Hemangioma^[17]
• Lymphoma^[17]
• Meningioma^[8]

Causes of EPC associated with cortical dysplasias include the following:

• Cortical dysplasia^{[18, 19, 20]}
• Hemimegalencephaly^[14]
• Tuberous sclerosis^[14]
• Linear sebaceous nevus syndrome^[14]
• Sturge-Weber syndrome^[14]

Infectious or parasitic causes of EPC include the following:

• Abscess^[16]
• Tuberculoma^[3]
• Gumma^[16]
• Russian spring-summer encephalitis^[16]
• Subacute measles encephalitis^[14]
• Human immunodeficiency virus (HIV)^[21]
• Progressive multifocal leukoencephalopathy^[22]
• Creutzfeldt-Jakob disease^[8]
• Viral encephalitis or meningo-encephalitis^[16]
• Cryptococcal meningitis^[23]
• Anti-Hu-associated paraneoplastic encephalitis^[24]
• Cysticercosis^[16]
• Granulomatous diseases^[16]
• Pertussis infection^[25]

Causes of EPC associated with vascular lesions include the following:

• Arteriosclerotic cerebrovascular disease^[16]
• Embolic or postthrombotic ischemic infarction^[16]
• Cortical venous thrombosis^[16]
• Cerebral hemorrhage^[16]
• Systemic lupus erythematosus^[14]
• Sjögren syndrome^[26]
• Arteriovenous malformation^[14]
• Carotid hypoplasia^[27]

Causes of EPC associated with traumatic lesions include the following:

• Acute head trauma^[28]
• Posttraumatic cyst^[16]
• Subdural hematoma^[16]
• Intracerebral hematoma^[16]
• Epidural hematoma^[16]

Drug-induced causes of EPC include the following:

• Penicillin^[16]
• Azlocillin^[29]
• Cefotaxime^[29]
• Metrizamide^[30]

Metabolic causes of EPC include the following:

• Diabetic ketoacidosis^[31]
• Nonketotic hyperglycemia^[32]
• Hepatic encephalopathy^{[5, 33]}
• Uremic encephalopathy^[5]
• Hyponatremia^[5]

Idiopathic causes of EPC include the following:

• Rasmussen chronic encephalitis^{[14, 16]}
• Autoimmune - Multiple sclerosis,^[34] anti-GluR3 or anti-NMDA-GluR-Epsilon2 antibodies
• Genetic

With regard to the last item above, genetic causes include Alpers disease, Kufs disease,^[35] Leigh syndrome and cytochrome C oxidase deficiency,^[36] nicotinamide adenine dinucleotide (NADH) coenzyme Q reductase deficiency,^[37] and mitochondrial cytopathies, including mitochondrial encephalopathy with lactic acidosis and stroke (MELAS)^[38]

Neurologic evaluation is essential in view of the variety of etiologies and associated illnesses in patients with epilepsia partialis continua (EPC).

In general, electroencephalography 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 of other seizure types or projected abnormalities suggestive of widespread, but lateralized, disease. Frequently, lateralized, asymmetrical 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 asymmetrical. 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 somatosensory evoked potentials (SSEP), have been used to examine the physiologic 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 scanning are emerging as useful research tools in the evaluation of the metabolic effects of epilepsia partialis continua (EPC), especially when computed tomography (CT) and magnetic resonance imaging (MRI) scan findings are normal.

PET scan 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 the diagnosis of EPC but also for its treatment.^[39]

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.^[14]

SPECT-MRI fusion has been reported by Matthews to have successfully been used to identify epileptic focus in a patient with EPC.^[40]

Burneo reported that ictal SPECT has also been useful in the presurgical evaluation of Rasmussen encephalitis.^[41]

The long-term prognosis of epilepsia partialis continua (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 neurologic decline.

In patients 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 should focus on the underlying condition. Antiepileptic drugs (AEDs) must be tried to prevent the spread of epilepsia partialis continua (EPC), but, with a few notable exceptions, they are unsuccessful in altering the course of EPC. Phenytoin or phenobarbital may be more effective than carbamazepine or valproate.^[14] Echenne reported a case of felbamate success in a patient with hemimegalencephaly and multiple types of seizures that responded poorly to AEDs.^[42]

Oral corticosteroid therapy and immunosuppression may be of some benefit in rare cases.^[16] A correlation has been found between Rasmussen encephalitis and serum antibodies to the glutamate receptor subunits, GluR3^[43] and NMDA-type GluR-Epsilon2.

Barrontini et al^[44] reported the use of gamma globulins, but few lasting benefits have been reported to date.Nimodipine has been administered successfully in 2 cases of EPC following an acute cerebral event.^[45]

Because cytomegalovirus has been implicated in the pathogenesis of Rasmussen syndrome, McLachlan et al^[46] 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.

A case of successful treatment of facial myoclonus with botulinum toxin for symptomatic relief from EPC was reported by Browner.^[47]

Transcranial magnetic stimulation has been reported to have lasting success in anecdotal cases and seems to deserve further evaluation.^{[48, 49]} Rotenberg reported patients with epilepsia partialis continua (EPC) who benefited from transient suppression of seizures by undergoing low-frequency transcranial magnetic stimulation.^[50]

Neurosurgical approaches, such as multiple subpial transections^[51] , 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.

Plasma exchange has been reported to have improved EPC significantly.