Epilepsia partialis continua
by Heinz Gregor Wieser
Date of submission: February 20, 2001
Date of update: January 2002
Date of update: February 28, 2003
Medline SEARCH DATE: February 2001

HISTORICAL NOTE AND NOMENCLATURE

Epilepsia partialis continua, or so-called "Kozhevnikov syndrome," was first described by Kozhevnikov in 1895 as a disorder characterized by persistent localized motor seizures (Kozhevnikov 1895). In his 4 cases, the seizure disorder consisted of frequent jerks that were resistant to treatment and continued for 3.5 to 5 years in the same part of the body. Kozhevnikov recognized the epileptic nature of these jerks and postulated a localized inflammation of the brain involving the motor strip. Omorokow reviewed 42 cases of "Kozhevnikov syndrome" in the literature and described a further 52 cases from his own Siberian clinic, recognizing that this form of epilepsy may be due to Russian spring-summer tick-borne encephalitis (Omorokow 1927; 1951). In 1958 Rasmussen, Olszewski, and Lloyd-Smith described 3 cases of persisting focal epilepsy due to chronic focal encephalitis. By 1988, a total of 48 Rasmussen chronic encephalitis cases had been identified and described (Oguni et al 1991), differing in many ways from those of Russian spring-summer tick-borne encephalitis (Andermann and Hart 2001). Since the first descriptions of epilepsia partialis continua, many localized cerebral disturbances have been found to give rise to similar patterns of ictal behavior (Schomer 1993), and the definition and nomenclature of epilepsia partialis continua was a subject of controversy. In 1966 Juul-Jensen and Denny-Brown pointed out that in various papers, the definition of epilepsia partialis continua was not the same. The authors asked for a distinct differentiation between true epilepsia partialis continua with "clonic muscular twitching repeated at fairly regular short intervals in one part of the body for a period of days or weeks," and focal epilepsy with motor seizures with frequent recurrence and with "Jackson march" or progression from tonic to clonic phase. Later, authors characterized epilepsia partialis continua as a "partial somatomotor status epilepticus for a minimum of 1 hour and recurring in intervals of no more than 10 seconds" (Thomas et al 1977), and as "spontaneous regular or irregular clonic twitching of cerebral cortical origin sometimes aggravated by action or sensory stimuli (reflex component) confined to one part of the body and continuing for a period of hours, days, or weeks" (Obeso et al 1985). In 1989 the International League Against Epilepsy Commission defined epilepsia partialis continua (Kozhevnikov) syndrome as a specific form of partial somatomotor seizure disorders involving the rolandic area of the motor cortex (Commission 1989). Schomer used epilepsia partialis continua and a focal status epilepticus as a synonymous term (Schomer 1993). At the May 1999 Verona meeting of the Epilepsy and Seizure Classification Working Group, it was decided that epilepsia partialis continua is not a recognized syndrome, but should be dealt with under the category "seizures-oriented topics" (Schomer 1993).



CLINICAL MANIFESTATIONS

Epilepsia partialis continua is characterized by almost continuous, rhythmic muscular contractions affecting a limited part of the body for a period of hours, days, or even years. The myoclonic jerks have a frequency of about 1 to 2 per second and may persist during sleep (Wieser et al 1978; Bancaud et al 1982; Perniola et al 1989). About 60% of the patients exhibit, in addition to an epilepsia partialis continua, other types of seizures (Cockerell et al 1996), such as secondary generalized seizures and complex partial seizures. In addition to muscle twitching, patients may show varying degrees of muscle weakness, sensory loss, or stretch reflex changes.

The presentation of the disorder depends on the underlying cause. Patients with localized neoplastic, vascular, or infectious brain lesions may have neurologic deficits and isolated seizures prior to the onset of the focal status (Bancaud 1985). With metabolic causes, however, such as nonketotic hyperglycemic diabetes mellitus, or hypersensitive reactions to certain drugs such as penicillin or metrizamide, the onset of focal status epilepticus is sudden (Schomer 1993).

In the Russian patients, the epilepsy usually developed 3 to 4 months after a febrile illness, associated with a hemiplegia or monoplegia in 30% of cases. In this condition the jerks typically affect agonist and antagonist muscles with a rhythmic quality, in short bursts of 1 to 2 seconds’ duration alternating with quiescent phases 2 to 4 seconds long, persisting in sleep and worsened by action or stress. Motor seizures with Jacksonian march or generalized epileptic seizures are almost invariable accompaniments, although with a strong tendency to improve over time. The jerking, often highly focal, continues relentlessly for years. Sensory symptoms occur in about one-fifth of cases, and 80% have a persisting hemiparesis. Epilepsia partialis continua associated with Rasmussen encephalitis manifests itself in children in the majority of cases (mean age 6.8 years with 85% being under the age of 10 years). All children present with epileptic seizures, often generalized tonic-clonic, although focal simple or complex partial seizures also occur as a first manifestation of the disease. In Rasmussen encephalitis, about half of the patients exhibit episodes of epilepsia partialis continua, usually within 3 years of onset with epilepsy. These episodes last hours to years and are often discontinuous. The condition is progressive, and after a highly variable period of 3 months to 10 years, fixed focal deficits develop, notably hemiplegia, hemianopia, and (depending on the hemisphere) aphasia, as well as progressive intellectual impairment. After an initial progressive course, in which the focal motor seizure activity is often multifocal motor, the disease process appears to eventually burn itself out, at least in a substantial proportion of Rasmussen encephalitis patients.



CLINICAL VIGNETTE

No information was provided by the author.


LOCALIZATION

Epilepsia partialis continua is a particular form of Rolandic partial epilepsy that involves the motor strip of one hemisphere and usually has a clinically localized appearance. In Rasmussen encephalitis the disease process seems to be more widespread with diffuse patchy inflammatory changes in the cortex and white matter (microglial nodules, perivascular cuffs of small lymphocytes and monocytes, multifocal neuronal loss, and some spongy degeneration) depending on the features of the disease activity. See also Robitaille, who classified the Montreal specimens into 4 groups of disease activity (Robitaille 1991).

Current views are that the physiological characteristics of the jerks in most cases of epilepsia partialis continua are identical to those of cortical myoclonus (see pathophysiology). In the past, though, an influential paper by Juul-Jensen and Denny-Brown reported the electrophysiological and pathological details of 9 patients with acute (mostly large) cerebral lesions with subcortical damage (albeit in most cases coexisting cortical motor area damage) (Juul-Jensen and Denny-Brown 1966). This paper created a controversy regarding cortical versus subcortical origin and the differentiation from myoclonus (Shorvon 1994).

The myoclonic jerks in epilepsia partialis continua can affect any muscle group. They may be confined to a single muscle or muscle group or they may be widespread. The distribution of jerks can vary over time. Agonists and antagonists are affected together, and distal muscles are affected more often than proximal. Face, upper limb, and trunk predominate. Jerks are unilateral. Bilateral cases have been included (Lohler and Peters 1974; Thomas et al 1977), but it is questionable whether such cases should be described within the category called epilepsia partialis continua. Takahashi and colleagues (Takahashi et al 1997) have studied epilepsia partialis continua of childhood involving bilateral brain hemispheres, and Ashkenazi and colleagues have described a bilateral focal motor status epilepticus with retained consciousness after stroke (Ashkenazi et al 2000).

Familial alternating epilepsia partialis continua with chronic encephalitis as another variant of Rasmussen syndrome has been described by Silver and colleagues (Silver et al 1998); Yacubian and colleagues (Yacubian et al 2001) described Rasmussen encephalitis associated with segmental vitiligo of the scalp.



PATHOPHYSIOLOGY

The definite proof for a cortical origin of epilepsia partialis continua was provided by 3 studies using depth-electrode-recordings (Bancaud et al 1970; Buser et al 1971; Wieser et al 1978). An experimental model of epilepsia partialis continua was achieved by injections of aluminum hydroxide into monkeys' motor cortex (Chauvel and Lamarche 1975). Using this experimental model, Chauvel and associates proved the role of the long-loop reflexes for generation of the cortical myoclonus (Chauvel et al 1989). Thermocoagulation of the thalamic Ncl vpl oralis disrupted the reflex loop and led, in the majority of cases, to a cessation of the myoclonus. The participation of the (presumably) ventrolateral and intralaminar thalamic nuclei (Jones et al 1979) in the epileptic process was illustrated on FDG-PET by a simultaneous metabolic increase in both the cortical and the ipsilateral thalamus in a patient with an epilepsia partialis continua (Hajek et al 1991).

However, absence of epileptogenic EEG abnormalities in some patients with epilepsia partialis continua (Penfield and Jasper 1954) and presence of subcortical brain lesions with preserved cortex (Juul-Jensen and Denny-Brown 1966; Botez and Brossard 1974) led to the hypothesis of a subcortical origin of the epilepsia partialis continua in at least some patients.

In 1985 Hallett introduced 3 types of epileptic myoclonus: (1) cortical reflex myoclonus as a fragment of partial epilepsy, which represents hyperactivity of a focal area of cerebral cortex; (2) reticular reflex myoclonus as a fragment of generalized epilepsy with hyperactivity of medullary brainstem reticular formation; and (3) primary generalized epileptic myoclonus as a fragment of primary generalized epilepsy, which may represent a generalized hyperactive response of cortex to subcortical input (Hallett 1985).

In cases with cortical reflex myoclonus, the epileptogenic focus is localized in the contralateral rolandic cortex, and the EEG may show spikes related to the myoclonic jerks. In cases without a clear-cut temporal relation between epileptic events and myoclonus in the EEG, the back-averaging technique identifies the spikes preceding the myoclonus (Shibasaki and Kuroiwa 1975). Somatosensory evoked potentials of the rolandic cortex are abnormally enlarged (Shibasaki et al 1978).

Without such proof of the cortical origin of the myoclonus by neurophysiological methods, a subcortical, or even spinal origin of the myoclonus has to be considered. Recently, Cockerell and colleagues suggested that the diagnosis of epilepsia partialis continua should be confined exclusively to cortical myoclonus (Cockerell et al 1996). The authors proposed the term "myoclonia continua" for myoclonus that arises extracortically.

In cases of epilepsia partialis continua where it is associated with other seizures, the physiological characteristics of the jerks are identical to those of cortical myoclonus (Shorvon 1994). Cortical myoclonus can be viewed as a hypersynchronous discharge from a group of cortical cells. In this sense, it is cortical epilepsy. Concerning myoclonus in general, by employing different physiological methods, such as back-averaging of EEG recordings in relation to the jerks, evoked potentials, and electromyographic recordings of the sequence of recruitment of muscle groups in a myoclonic jerk, a distinction of myoclonus into cortical, brainstem, and spinal myoclonus is possible in most cases. Typically in cortical myoclonus, back-averaged time-locked EEG cortical generator potentials precede the jerks; sensory evoked potentials are enlarged; and the myoclonus may be spontaneous and action- or stimulus-sensitive with a rostrocaudal pattern of muscle recruitment and antagonist and agonist co-contraction. In stimulus-sensitive myoclonus, the reflex timings are compatible with a cortical loop. Obeso and colleagues report patients showing a spectrum of spontaneous and stimulus-sensitive myoclonus, epilepsia partialis continua, Jacksonian seizures, and generalized seizures, all with similar physiology (Obeso et al 1985). In these cases it is hard to escape the view that epilepsia partialis continua is simply repetitive cortical myoclonus. However, in cases without seizures other than epilepsia partialis continua, jerks resemble epilepsia partialis continua clinically but not neurophysiologically. In these cases the jerks might be of subcortical origin. Menini and Naquet called this variant type C myoclonus with suggested origin in the brainstem (Menini and Naquet 1986). It is, however, fair to say that this variety is not as common nor as well studied as the cortical myoclonus, and its exact nosological position is not clear.


DIFFERENTIAL DIAGNOSIS

The differential diagnosis depends on the definition of epilepsia partialis continua. If the diagnosis of epilepsia partialis continua is based on the presence of cortical myoclonus, the diagnosis (and consequently the differential diagnosis) requires extensive electrophysiological verification. If the diagnosis of epilepsia partialis continua is based on the clinical appearance alone, a differentiation between cortical and subcortical origin is not possible. If one considers Rasmussen encephalitis a distinct syndrome from Kozhevnikov epilepsia partialis continua, it has to be mentioned here because approximately 50% of Rasmussen encephalitis patients exhibit epilepsia partialis continua.

The differential diagnosis of myoclonus is difficult. The Commission on Pediatric Epilepsy of the ILAE grouped myoclonus into (1) cortical myoclonus, (2) thalamocortical myoclonus, (3) reticular reflex myoclonus, and (4) negative myoclonus (Commission on Pediatric Epilepsy of the ILAE 1997). According to this Commission report, epileptic myoclonus should be distinguished from:

  1. Nonmyoclonic epileptic seizures, including spasms that are more prolonged, occur in clusters, and are combined with a high-amplitude EEG slow-wave. Spasms should be distinguished from tonic seizures, which are associated with EEG low-amplitude fast activity. Some seizures are biphasic, including myoclonic-atonic, myoclonic-spasm, or spasm-tonic seizures.
  2. Nonepileptic myoclonus, including opsoclonus-myoclonus syndrome, in which myoclonus is nearly continuous, erratic, and movement-induced. Sleep myoclonus may affect normal newborns or infants and also newborns with cerebral palsy. Myoclonus may occur in progressive dystonia. Normal startle responses result from activation of brainstem centers. The most common exaggeration of the startle reflex is manifest in hyperexplexia.
  3. Nonepileptic, nonmyoclonic phenomena, particularly tremor in which the contraction affects agonist and antagonist muscles alternatively and is more rhythmic than myoclonus. Tics last 200 ms, and the frequency may be altered voluntarily. In chorea, the frequency is irregular, lasting 50 ms to 750 ms, and is asynchronous in antagonist muscles.
    Periodic leg movements of sleep are characterized by a periodicity of 10 to 90 seconds in sleep (Montplaisir and Godbout 1989).

Myoclonus may combine with epilepsy in various conditions:

  1. Myoclonus in progressive encephalopathies. Unverricht-Lundborg disease and inborn errors of metabolism such as Lafora body disease are listed under this category. In all progressive encephalopathies, the hallmark is giant somatosensory-evoked potentials.
  2. Myoclonus in nonprogressive generalized epilepsy mainly involves idiopathic generalized epilepsy and is of thalamocortical type. This includes benign myoclonic epilepsy of infancy, juvenile myoclonic epilepsy, myoclonic absences, severe myoclonic epilepsy of infancy, and myoclonic astatic epilepsy with favorable and unfavorable outcome. The latter resembles cryptogenic Lennox-Gastaut syndrome.
  3. Myoclonus in congenital nonprogressive encephalopathies of various causes, including malformations or chromosome aberrations (ie, Angelman syndrome).
  4. Neonatal myoclonic encephalopathy (ie, burst of massive myoclonus and an EEG suppression-burst pattern) due to inborn errors of metabolism or cryptogenic in origin.
  5. Myoclonic status is often encountered in severe myoclonic epilepsy of infancy and myoclonic astatic epilepsy.

Epileptic negative myoclonus may be generalized or focal. Epileptic negative myoclonus is a heterogeneous condition that may originate from various brain areas, including premotor cortex and motor cortex. It may be correlated with the slow wave of a spike-wave complex (as in the syndrome of continuous spike waves during slow-wave sleep) or with the negative transient of the polyspike of a polyspike-wave complex (as in myoclonic absence). Symptomatic generalized epileptic negative myoclonus due to Lance-Adams syndrome may be combined with positive myoclonus.

Asterixis was reported to be misdiagnosed for an epilepsia partialis continua (Stell et al 1994), as was Parkinson disease (Al-Hayk and LeDoux 2003). Dystonia, athetosis, and epilepsia partialis continua was reported in a patient with late-onset Rasmussen encephalitis (Frucht 2002). Andermann and colleagues described the syndrome of prolonged classical migraine, epilepsia partialis continua, and repeated strokes as a clinically characteristic disorder probably due to mitochondrial encephalopathy (Andermann et al 1986). Varlamov and colleagues (Varlamov et al 2002) have identified a novel heteroplasmic C6489A missense mutation in the mitochondrial DNA (mtDNA) CO I gene encoding the cytochrome c oxidase subunit I in a 17-year-old girl with epilepsia partialis continua.



DIAGNOSTIC WORKUP

Every case with an epilepsia partialis continua requires a general medical and neurologic evaluation to search for a metabolic or hereditary disorder. If this kind of workup is inconclusive or normal, structural imaging with MRI often reveals a brain lesion. Functional neuroimaging with SPECT, PET, or fMRI may be helpful in identifying the origin of the myoclonus. The EEG may show focal spikes and slowing in the central area, but there are no characteristic EEG patterns that aid in diagnosis of this specific type of epilepsy. In cases without a conclusive EEG, the back-averaging technique may help to identify the spikes preceding the myoclonus. In Rasmussen encephalitis, the documentation of a progressive atrophy of usually one hemisphere is important.

Relatively characteristic, other pathological findings in MRI and MR-spectroscopy as well as pathological SPECT and PET findings may be helpful for the early diagnosis and particularly for targeting the often intended brain biopsy. A moderately to severely abnormal EEG with progressive slowing and spiking is the rule. It is important to note that CSF may be abnormal with elevation of protein and lymphocytes, but a normal CSF does not rule out the presence of Rasmussen encephalitis.

Kim and colleagues (Kim et al 2002) studied 7 children with Rasmussen syndrome in a prospective longitudinal MRI study with 3 to 8 MRIs per patient performed between 12 months before and 9 months after the onset of epilepsia partialis continua. These authors described that the most common region of initial MRI signal change was the frontocentral region (6 patients). Three patterns of neuroimaging abnormalities were observed as follows:

  1. normal MRI followed by increased signal intensity with progressive cortical atrophy over time,
  2. initial increased focal signal intensity followed by decrease in spatial extent and degree of signal intensity;
  3. initially increased signal intensity without further changes on follow-up scans. The authors conclude that this observation suggests 3 possible distinct patterns of MRI changes in patients with Rasmussen syndrome, and that the differences in these neuroimaging patterns may reflect inherent differences in the pathogenesis of Rasmussen syndrome.

Park and colleagues (Park et al 2000) performed magnetic resonance spectroscopy in 3 pediatric patients with epilepsia partialis continua measuring the spectral peaks of several metabolites (N-acetyl-aspartate, choline, creatine, and lactate) and observed increased lactate-to-creatine ratios and reduced N-acetyl-aspartate-to-creatine ratios in the affected hemispheres in all 3 children with epilepsia partialis continua. These data support previous reports.



SYNDROMES AND DISEASES IN WHICH THE SEIZURE TYPE OCCURS

Syndromes and diseases in which the seizure type occurs
Epilepsia partialis continua is a rare condition with a wide range of underlying pathologies. Articles about epilepsia partialis continua include case reports or small series of patients. For this reason, no epidemiological data exist. Based on their survey of all registered cases in the United Kingdom during 1993, Cockerell and colleagues estimated the prevalence of epilepsia partialis continua to be less than 1 per million (Cockerell et al 1996).

Kozhevnikov suggested, without neuropathological evidence, that the myoclonic jerks originate in the cerebral cortex due to a localized encephalitis (Kozhevnikov 1895). Thirty years later, Omorokow proved the Kozhevnikov hypothesis in a series of 52 patients by performing numerous cortical biopsies (Omorokow 1927). Today, Kozhevnikov cases are believed to have been due to an infectious agent known as Russian spring summer encephalitis (Zemskaya et al 1991). Bancaud and colleagues delineated 2 epilepsia partialis continua syndromes (Bancaud et al 1982). These authors assigned the epilepsia partialis continua type I to a localized pathology of the rolandic cortex, whereas epilepsia partialis continua type II was assigned to a diffuse unilateral encephalitic process. Encephalitic epilepsia partialis continua is the most frequent form in childhood and is related to Rasmussen syndrome (Rasmussen et al 1958).

In short, the clinical picture of this "chronic encephalitis" is characterized by a severe focal seizure tendency beginning in infancy and childhood, often associated with epilepsia partialis continua. Patients with epilepsia partialis continua show a slowly progressive neurologic deterioration, usually hemiparesis and mental retardation, which advances over periods of months or years before the progression becomes arrested (Oguni et al 1991). With few exceptions, the pathological process with a gradual destruction of brain tissue involves one hemisphere only. The majority of patients with Rasmussen encephalitis exhibit an inflammatory episode of some sort at, or shortly before, the onset of seizures. In relatively well-preserved brain areas, perivascular lymphocytic cuffs and glial nodules, and in later stages microcystic degeneration with marked neuronal fallout but without evidence of inflammatory elements are typical histological findings (Robitaille 1991). It is fair to say that the nature of this disease remains obscure, although in recent years an autoimmune process has been postulated, as prompted by various reports (Rogers et al 1994; Twyman et al 1995; Andrews et al 1996). Autoantibodies in sera from patients with active Rasmussen encephalitis and experimentally-induced antibodies in rabbits seemed to act as agonists for glutamate receptors consisting of or containing GluR3 subunits. Agonist activity of autoantibodies on a glutamate receptor subunit suggested their role as pathogenetic factors, potentially as highly specific excitotoxins or neuromodulators. Our search, however, for the presence of anti-GluR3 antibodies in sera and CSF of 4 patients with Rasmussen encephalitis yielded negative results (Tonnes et al 1998).

Today it is generally accepted that epilepsia partialis continua may be associated with focal, multifocal, and diffuse brain lesions and may include numerous syndromes. In children, besides the Rasmussen encephalitis, the other main causes for an epilepsia partialis continua are multisystem degenerative diseases, such as mitochondrial disorders (Andermann et al 1986; Carrascosa et al 1990; Antozzi et al 1995; Veggiotti et al 1995), or the Alpers syndrome (Wilson et al 1993; Worle et al 1998; Rasmussen et al 2000).

In adults, epilepsia partialis continua is most frequently related to atherosclerotic cerebral vascular diseases, strokes, and tumors. Less frequent causes are metabolic disturbances, such as nonketotic hyperglycemic diabetes mellitus, particularly associated with hyponatremia (Singh and Strobos 1980), renal and hepatic encephalopathy (Morres and Dire 1989), and cortical dysplasia (Nordborg et al 1987; Desbiens et al 1993). Epilepsia partialis continua has also been associated with multiple sclerosis, mitochondrial encephalopathy with lactic acidosis and strokes, mitochondrial encephalopathy with ragged red fibers, and MELAS plus syndrome (Peterus et al 1997).

Epilepsia partialis continua as the first clinical manifestation has been described in progressive cerebral degeneration of childhood with liver disease (Alpers Huttenlocher disease) with cytochrome oxidase deficiency (Worle et al 1998) as well as in a patient with a missense mutation in the mitochondrial DNA CO I gene encoding the cytochrome c oxidase subunit I (Varlamov et al 2002). This point mutation leads to an exchange of the highly conserved Leu196 to Ileu196. Muscle biopsy showed in single fibers decreased cytochrome c oxidase activity and lowered binding of cytochrome c oxidase antibodies, indicating decreased stability of the mutated enzyme. The analysis of blood mtDNA revealed about 30% mutant mtDNA in the patient's blood.

Epilepsia partialis continua has been observed in Creutzfeldt-Jakob disease (Lee et al 2000; Parry et al 2001) and succeeding bone marrow transplants (Antunes et al 2000). It was observed in association with widespread gliomatosis cerebri (Shahar et al 2002), as an atypical presentation of cat scratch disease in a young adult (Nowakowski and Katz 2002), in association with type 1 diabetes mellitus and elevated anti-GAD65 antibodies (Olson et al 2002), in ketotic and nonketotic hyperglycemia (Placidi et el 2001; Sabitha et al 2001), and in HIV-infected patients (Ferrari et al 1998; Bartolomei et al 1999). Kufs disease presented as late-onset epilepsia partialis continua (Gambardella et al 1998).

Epilepsia partialis continua has been described in association with a homoplasmic mitochondrial tRNA (Ser(UCN)) mutation (Schuelke et al 1998), as a new manifestation of anti-Hu-associated paraneoplastic encephalomyelitis (Shavit et al 1999; Porta-Etessam et al 2001).

Epilepsia partialis continua has also been found in benign epilepsy of childhood with centrotemporal spikes. Metrizamide, penicillin, and azlocillin-cefotaxime may also induce this disorder (Schomer 1993).


PROGNOSIS AND COMPLICATIONS

Prognosis and complications
The long-term prognosis of epilepsia partialis continua depends on the underlying disorder. When it appears early in the course of a metabolic disturbance, the condition may be benign. Iatrogenic epilepsia partialis continua induced by certain antibiotics and metrizamide disappears with removal of the offending agent. Epilepsia partialis continua associated with benign childhood epilepsy syndromes with Rolandic foci usually respond to treatment with antiepileptic medication. In epilepsia partialis continua associated with Russian spring-summer encephalitis, convulsive movements continue relentlessly over many years and are uninfluenced by medical therapy; surgical excision seems to offer the only hope of remission. Epilepsia partialis continua due to Rasmussen encephalitis has an almost invariably poor outcome with respect to the function of the affected hemisphere. There seems to be a progressive phase (mean of 5.3 years in one series of 48 patients), and the condition then becomes static (Oguni et al 1991). Death is exceptional, as eventually the condition stabilizes, although with severe disability. In many cases with epilepsia partialis continua due to Rasmussen encephalitis, a functional hemispherectomy is the only effective treatment option. In a few exceptional patients, the epilepsia partialis continua disappeared after some months to years, suggesting that the disease can "burn out." These few observations are in opposition to the opinion that in very rare cases Rasmussen encephalitis may also affect the opposite hemisphere. Other forms of epilepsia partialis continua, although not progressive, also usually respond poorly to antiepileptic medication but may disappear with time or resolve with surgical excision of a focal lesion. There may be associated weakness in muscle groups involved in the clonic activity, which can persist when the epilepsia partialis continua abates. It is unclear to what extent this may be due to the persistent epileptic discharges, and to what extent the residual neurologic deficit is due to the underlying lesion. In the retrospective series of Thomas and colleagues of 26 patients with epilepsia partialis continua of various causes, 11 patients were alive and 15 had died after a follow-up of 1 to 18 years. Outcome was largely determined by the underlying cause, and seizures were more likely to remit in patients with stroke or other acute insults than in encephalitis cases (Thomas et al 1977).


MANAGEMENT

Treatment of epilepsia partialis continua should concentrate on the underlying cause when possible. The management of iatrogenic and metabolic disturbances is apparent. The major antimyoclonic drugs are piracetam, valproate and ethosuximide, and benzodiazepines (clonazepam). Antiepileptic drugs such as sulthiame and carbamazepine may be effective in treating epilepsia partialis continua associated with benign childhood epilepsies and centrotemporal spikes. Other causes of Bancaud type I epilepsia partialis continua tend to be refractory to antiepileptic drugs. In single case reports, therapeutic success was achieved by nimodipine, a calcium-channel blocker (Brandt et al 1988), and by clonazepam (Schomer 1993). In addition to conventional antiepileptic drug therapy, steroid administration may be indicated in epilepsia partialis continua. In Cockerell’s study of 36 patients, the epilepsia partialis continua resolved in 4 patients and persisted in the remaining 32 patients. In cases with Bancaud type I epilepsia partialis continua, the appropriate therapy is surgical excision of the structural lesion. When the epileptogenic region involves the primary motor cortex, multiple subpial transection may be an option. Multiple subpial transection can eliminate seizures without inducing severe additional neurologic deficit (Patil et al 1997; Molyneux et al 1998; Morell et al 1989). In Rasmussen encephalitis, many authors consider functional hemispherectomy as the only effective treatment. Usually, however, it is only performed at a relatively late stage, ie, not before a hemiparesis already exists. With the assumption that the cause of Rasmussen encephalitis is either infective, probably viral, or the result of an autoimmune process, ganciclovir, zidovudine, high-dose interferon, high-dose steroids and immunoglobulins, and plasmapheresis have been tried. A beneficial influence of plasmapheresis observed in 2 studies (Rogers et al 1994; Andrews et al 1996) led us to introduce a combined treatment with plasmapheresis and CSF filtration in 2 patients with some initial but no long lasting effect (Wieser 1996; Wieser et al 1996).

Antozzi and colleagues (Antozzi et al 1998) reported that long-term selective IgG immunoabsorption improves Rasmussen encephalitis; Dabbagh and colleagues (Dabbagh et al 1997) could stop seizures by intraventricular interferon-alpha in one case of Rasmussen encephalitis. In the case of Olson and colleagues (Olson et al 2002), with the diagnosis of type 1 diabetes and antiglutamic acid decarboxylase 65 antibodies in his serum and cerebrospinal fluid, antiepileptic agents did not improve his seizures, but high-dose steroids, plasmapheresis, and intravenous immunoglobulin resulted in decreased antiglutamic acid decarboxylase 65 antibody levels and resolution of his seizures.

At present, when the diagnosis of Rasmussen encephalitis is being considered, it is important to rapidly exclude other causes of epilepsia partialis continua. Although there are no good data from randomized trials of different immune-related therapies, treatment with immunoglobulin G, steroids, or plasmapheresis is advocated as first-line therapy. It is not unreasonable to institute at least 2 treatment options (eg, IgG followed by plasmapheresis) if response to the first treatment is poor (Counce et al 2001). Functional hemispherectomy and its variants are associated with a lower long-term complication rate.



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ILAE

ILAE Copyright Notice

ABBREVIATIONS

EEG:electroencephalography
EMG:electromyography
FDG-PET:19-fluorodeoxyglucose positron emission tomography
SPECT:single photon emission tomography
PET:positron emission tomography
MRI:magnetic resonance imaging
fMRI:functional magnetic resonance imaging

SYNONYMS

Epilepsia partialis continua Bancaud type I
Focal motor epilepsia partialis continua
Focal motor status epilepticus
Kozhevnikov syndrome
Partial motor status epilepticus

MAJOR KEYWORD DESCRIPTORS

agonist muscles
antagonist muscles
brain lesions
cerebral cortex
muscle contractions
myoclonic jerks
reflex change
sensory loss
status epilepticus

MINOR KEYWORD DESCRIPTORS

seizures
twitching

AGE OF PRESENTATION

0-01 month
01-23 months
02-05 years
06-12 years
13-18 years
19-44 years
45-64 years
65+ years

AGE OF TYPICAL PRESENTATION

0-01 month
01-23 months
02-05 years
06-12 years
13-18 years
19-44 years
45-64 years
65+ years

GLOSSARY
epilepsia partialis continua:a particular form of partial status epilepticus characterized by continuous focal clonic motor seizures

ILLUSTRATION CAPTIONS

Figure 1 (not included because clinical vignette cut from seizure-oriented structure--dlc)
Position of the electrodes on the standard brain map with lateral and antero-posterior views. Technical details of the electrodes: No. 1-7: gold, diameter 700-800 µm, contact length 1.7 mm each, intercontact spacing 1.7 mm, impedance ˜30 kO (50c/sec, 0.3 V); No. 9: silver, diameter 2.4 mm, contact length 1.5 mm, intercontact spacing 1.5 mm, impedance < 5 kO (50 c/sec, 0.1 V).

PERMUTED TOPIC, SYNONYMS, VARIANTS

Epilepsia partialis continua of Kozhevnikov
partialis continua of Kozhevnikov, Epilepsia
continua of Kozhevnikov, Epilepsia partialis
Kozhevnikov, Epilepsia partialis continua
partialis continua Bancaud type I, Epilepsia
continua Bancaud type I, Epilepsia partialis
Bancaud type I, Epilepsia partialis continua
motor epilepsia partialis continua, Focal
epilepsia partialis continua, Focal motor
partialis continua, Focal motor epilepsia
continua, Focal motor epilepsia partialis
motor status epilepticus, Focal
status epilepticus, Focal motor
epilepticus, Focal motor status
syndrome, Kozhevnikov
motor status epilepticus, Partial
status epilepticus, Partial motor
epilepticus, Partial motor status

RELATED TOPICS

Arboviral encephalitis
Epilepsy
Headache associated with meningitis, encephalitis, and brain abscess
Hemimegalencephaly
Hyperglycemic hypersmolar nonketotic state
Limbic status epilepticus (psychomotor status)
Myoclonus
Rasmussen syndrome

DIFFERENTIAL DIAGNOSIS

Rasmussen encephalitis
cortical myoclonus
thalamocortical myoclonus
reticular reflex myoclonus
negative myoclonus
nonmyoclonic epileptic seizures
tonic seizures
myoclonic-atonic seizures
myoclonic-spasm seizures
spasm-tonic seizures
opsoclonus-myoclonus
sleep myoclonus
progressive dystonia
hyperexplexia
nonepileptic, nonmyoclonic phenomena
tics
chorea
Unverricht-Lundborg disease
Lafora body disease
epileptic negative myoclonus
asterixis

 

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