Myoclonus epilepsy with ragged-red fibers
Jun. 10, 2021
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Epilepsia partialis continua is a rare form of simple focal motor status epilepticus of mainly cerebral cortical origin. It manifests with repetitive, regular, or irregular localized clonic muscle twitching, lasting for a few milliseconds and repeated at least every 10 seconds for hours, days, or months without impairment of consciousness. Onset occurs at any age, but starts before 16 years of age in a third of cases. Both sexes are equally affected. Prevalence is extremely small, probably less than 1 per million population.
Causes are multiple and diverse. Rasmussen syndrome and malformations of cortical development are the main causes in children; cerebrovascular disease and brain space-occupying lesions are the main causes in adults. Nonketotic hyperglycemia is the most common reversible cause. The long-term prognosis is cause-dependent and usually poor. Most patients will continue with intractable epilepsia partialis continua and also develop neurologic and cognitive defects. Only a few patients may have a remission. Epilepsia partialis continua is typically drug resistant. When resective surgery is not possible, successful treatment with multiple subpial transections has been reported in a minority of operated patients. In this update, the author details the historical aspects, classification, clinical manifestations, pathophysiology, diagnostic workup, differential diagnosis, and management of epilepsia partialis continua, paying particular attention to recent advances.
• Epilepsia partialis continua is a rare type of simple focal motor status epilepticus characterized by continuous, involuntary focal muscle jerking of mainly cortical origin occurring at least every 10 seconds for at least 1 hour and not impairing awareness.
• Epilepsia partialis continua is a rare condition with a wide range of underlying etiologies; in children, the most common cause is Rasmussen syndrome, and in adults, the most common causes are cerebrovascular disease and neoplasm.
• Epilepsia partialis continua is typically resistant to medications, and whenever possible, treatment should focus on the underlying cause.
• The outcome of epilepsia partialis continua is variable and is highly dependent on underlying cause: seizures are more likely to remit in patients with stroke or other acute insults than in patients with chronic encephalitis.
In 1894 Aleksei Yakovlevich Kozhevnikov gave a superb description of “corticalis sive partialis continua” by detailing the clinical manifestations of 4 patients, localized the cause around the motor center, and accurately attributed the disease to chronic encephalitis (39; 40).
See English translation by Asher and Gadjusek and other details in more recent publications (02; 75; 44; 76; 27).
Encephalitis as a definite cause of epilepsia partialis continua was also established in the Western literature by Wilson and Winkelman in 1924 who described 3 cases with neuropathologic confirmation (81).
Omorokov reviewed 42 cases of “Kozhevnikov syndrome” (as he called it) in the literature and described a further 52 cases from his Siberian clinic (Omorokov 1927). Many of his cases with epilepsia partialis continua in Siberia (Kozhevnikov was practicing in Moscow) had acute encephalitis, and a few had cysticercosis. It was much later in 1937 that patients with acute encephalitis and epilepsia partialis continua proved to have Russian spring-summer tick-borne encephalitis (Omorokov 1927; 54; 76; 48).
Dereux described over 100 cases of Kozhevnikov syndrome, with many having chronic encephalitis (21).
Subsequently, Theodore Rasmussen documented epilepsia partialis continua as a cause of chronic encephalitis in children (60; 59).
In 1966, Juul-Jensen and Denny-Brown published a case series and review of the literature, observing that epilepsia partialis continua could be caused by several pathologic lesions in both cortical and subcortical structures (35). They proposed a definition of the clinical syndrome as “clonic muscle twitching repeated at fairly short intervals in 1 part of the body for a period of days or weeks.” They suggested that this syndrome differed from most focal epilepsies because in epilepsia partialis continua, there is no progression from the tonic to clonic phase and no Jacksonian march from 1 body area to another.
In 1974, Thomas and colleagues refined the definition of epilepsia partialis continua, based on the review of the clinical characteristics of 32 patients, as a syndrome “characterized by regular or irregular clonic muscular twitches affecting a limited part of the body, occurring for a minimum of 1 hour, and recurring at intervals of no more than 10 seconds” (72).
In 1985, Obeso and colleagues added 3 additional features to this definition: (1) the muscle jerks should occur spontaneously, (2) action and somesthetic stimuli could provoke jerks in some patients, and, perhaps most significantly, (3) the movements should be of cortical origin (50).
In 1996, Cockerell and colleagues reported 16 patients who underwent detailed clinical and neurophysiological assessments: only 6 had direct EEG and EMG evidence of a cortical origin of their jerks; 5 patients had indirect evidence of a cortical origin; 2 did not have myoclonus of cortical origin but of some other source (brainstem and basal ganglia); and the origin in the remaining 3 patients was uncertain. The authors simplified the definition of epilepsia partialis continua to “continuous muscle jerks of cortical origin” and suggested the term “myoclonia continua” for situations in which the cause is extracortical (16).
In 2011, a European survey and analysis of 65 cases of the clinical course and variability of non-Rasmussen, nonstroke, motor and sensory epilepsia partialis continua was published (44).
Other authors have noted that epilepsia partialis continua can be defined in 2 ways: based on the clinical features alone, or by combining clinical with neurophysiologic evidence to confirm the cortical origin of the abnormal movements (08). The previous authors of this article proposed maintaining many of the aspects of the above definitions, defining epilepsia partialis continua, as with other epileptic syndromes, based on combined clinical, neurophysiologic, and diagnostic imaging features. Epilepsia partialis continua is a continuous, involuntary focal muscle jerking of cortical origin occurring at least every 10 seconds for at least 1 hour and not impairing awareness.
ILAE classification, nomenclature, and definition. The ILAE Commission on Classification in 1985 recognized “two types of Kozhevnikov’s syndrome, but only 1 of these 2 types is included among the epileptic syndromes of childhood, because the other one is not specifically related to this age” (17).
“Kozhevnikov syndrome type 1” referred to epilepsia partialis continua and was defined as follows:
This type represents a particular form of rolandic partial epilepsy in both adults and children and is related to a variable lesion of the motor cortex. Its principal features are: (a) motor partial seizures, always well localised; (b) often late appearance of myoclonus in the same site where somatomotor seizures occur; (c) an EEG with normal background activity and a focal paroxysmal abnormality (spikes and slow waves); (d) occurrence at any age in childhood and adulthood; (e) frequently demonstrable aetiology (tumor, vascular); and (f) no progressive evolution of the syndrome (clinical, electroencephalographic, or psychological). This condition may result from mitochondrial encephalopathy (MELAS).
“Kozhevnikov type 2 syndrome” was defined as:
Childhood disorder, suspected to be of viral etiology, has onset between 2 and 10 years (peak, 6 years) with seizures that are motor partial seizures but are often associated with other types. Fragmentary motor seizures appear early in the course of the illness and are initially localized but later become erratic and diffuse and persist during sleep. A progressive motor deficit follows, and mental deterioration occurs. The EEG background activity shows asymmetric and slow diffuse delta waves, with numerous ictal and interictal discharges that are not strictly limited to the Rolandic area.
In the 1989 ILAE classification, Rasmussen syndrome was introduced as a synonym of Kozhevnikov type 2 syndrome (18). In subsequent ILAE revisions on classification and terminology (23; 22), the name Kozhevnikov was removed (56). The revision of seizure terminology by the ILAE Commission on Classification and Terminology lists Rasmussen syndrome under the category “distinctive constellations” (07), a name that is now abandoned (Commission on Classification and Terminology of the International League Against Epilepsy 2014).
Epilepsia partialis continua of Kozhevnikov is a seizure type (23; 22), though this is not mentioned in the ILAE positional papers of the operational classification of seizure types (26; 25).
According to the ILAE epilepsy diagnosis manual, “Epilepsia partialis continua refers to recurrent focal motor seizures (typically affecting hand and face, although other body parts may be affected that occur every few seconds or minutes for extended periods (days or years). The focal motor features may exhibit a Jacksonian march. A Todd’s paresis may be seen in the affected body part” (Commission on Classification and Terminology of the International League Against Epilepsy 2014).
In the most recent ILAE report on the definition and classification of status epilepticus, epilepsia partialis continua is listed amongst those with prominent focal motor symptoms (73).
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