Sustained Effect of Botulinum Neurotoxin in Myoclonus Owing to Epilepsia Partialis Continua

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Video 1

Video 1. Patient 3. EPC of the left arm presenting with continuous, irregular myoclonic activity during movement and rest before BoNT treatment. Additionally, some dystonic posturing of the hand underlies myoclonus (UMRS: rest 12/action 16).

Video 2

Video 2. Patient 3. EPC of the left arm, 3 weeks after BoNT treatment. Myoclonus at rest has abated and is mild with movement. However, dystonic posturing of the hand becomes more apparent (UMRS: rest 0/action 6).

Video 3

Video 3. Patient 3. EPC of the left arm, 3 weeks after BoNT treatment. Myoclonus at rest has abated and is mild with movement. However, dystonic posturing of the hand becomes more apparent (UMRS: rest 0/action 6).

Video 4

Video 4. Patient 4. EPC of the left face and platysma, 2 weeks after BoNT treatment, without myoclonus during speech or resting (UMRS: not rated).

Video 5

Video 5. Patient 4. EPC of the left face and platysma, 3 weeks after BoNT treatment. Myoclonus re-emerges only with activation of the platysma (UMRS: rest 0/action 4).

Authors:  Janis Rebecca Bedarf, Milena Marek, Christian G. Bien, Christian E. Elger and Sebastian Paus

Article first published online:  15 JUL 2015 | DOI: 10.1002/mdc3.12216



Epilepsia partialis continua (EPC) is defined as continuous myoclonic jerking of a body part of cortical origin and often resembles a movement disorder. Unfortunately, anti-epileptic therapy is frequently ineffective. Currently, the effect of botulinum neurotoxin (BoNT) therapy in EPC is controversial.


We analyzed case histories, treatment protocols, and video documentation of 5 patients with EPC, who received BoNT therapy in our movement disorders unit. The Unified Myoclonus Rating Scale was used to document treatment effects.


In all patients, BoNT treatment significantly reduced severity and frequency of myoclonus and led to pronounced improvement of speech and arm utilization, regardless of etiology or duration of EPC.


BoNT represents a safe, effective treatment in EPC, offering long-term abatement of myoclonus. The substantial functional profit may hint at mechanisms beyond local impairment of neuromuscular transmission, such as modulation of maladaptive cortical plasticity, as observed in dystonia and poststroke spasticity.

Epilepsia partialis continua (EPC) is a focal epileptic status,[1] presenting clinically as ongoing clonic muscular twitches of a body part.[2]Most likely, EPC is of focal cortical origin,[3] and electrophysiological studies revealed cortical reflex myoclonus as the main mechanism underlying EPC.[4] However, there is some evidence that subcortical structures, probably corticothalamic loops, are involved in the abnormal excitation maintaining EPC.[5] Juul-Jensen and Denny-Brown suggested an indispensable subcortical contribution to the genesis of EPC.[6] Based on detailed lesion analysis of 9 individual EPC cases and a literature review, they concluded that a diffuse impairment of extrapyramidal function is a necessary background for the occurence of the disorder. EPC is observed in various diseases leading to dysfunction of the motor cortex, notably vascular lesions, encephalitides, and metabolic disorders.[7] The most frequent cause of EPC in younger patients is Rasmussen encephalitis (RE), an immune-mediated brain inflammation of the cortex leading to hemispheric atrophy, which commonly involves the basal ganglia.[8]

The myoclonic muscle activity in EPC, sometimes aggravated by sensory stimulation or movement, often causes serious disability and limits the patient's autonomy. Unfortunately, although the disorder is classified as a focal status epilepticus, antiepileptic drugs (AEDs) are notoriously ineffective in patients with EPC, and there is little evidence to guide therapy.[9, 10] EPC often resembles a movement disorder, such as hemifacial spasm or tremor, and discrimination can be difficult.[7] For various hyperkinetic movement disorders, injections of botulinum neurotoxin (BoNT) are the treatment of choice,[11] owing to the fact that BoNT impairs neuromuscular transmission by inhibiting presynaptic acetylcholine release at the neuromuscular junction. Additionally, BoNT treatment might improve abnormal central reorganization in some central nervous system disorders.[12] BoNT was used to ameliorate EPC before; however, current literature reports only 5 cases, with controversial results of treatment.[13-16] Here, we present a new series of 5 patients suffering from medication-resistant EPC with myoclonus of face and arm, who had repeated BoNT treatment, in 2 cases over the course of 2 years or more.



We analyzed case histories and treatment protocols of all patients with EPC, who were assigned to our movement disorders unit from 2006 to 2013. Also, when available, video documentation was reviewed. Diagnosis of EPC was based on current clinical and electrophysiological features.[2-4] To document severity of myoclonus in affected body parts, subscales for face and arm of the Unified Myoclonus Rating Scale (UMRS) were used, considering myoclonus at rest and with action, respectively.[17] Each UMRS subscore is calculated as a product of frequency (range, 0–4) and amplitude (range, 0–4) of myoclonus, yielding a top result of 16. The subscale for facial myoclonus was modified to include the platysma, where appropriate. We considered UMRS subscores before initiation of BoNT therapy and 2 to 3 weeks after the latest injection. Treatment effects were determined as a relative reduction of UMRS subscores.

Effects of BoNT treatment on daily functioning were monitored by individual questions concerning routine activities. Furthermore, patients were asked to perform exemplary tasks, such as grasping a glass from the table, imitating brushing of the teeth (patients 1, 2, and 3), or drinking a glass of water (patients 1, 2, and 4), where appropriate. Also, treatment effects became obvious during routine neurological examinations.

The study involved no intervention purely for research. All analyses were retrospective. As such, no approval of the local ethics committee was needed. All patients gave written informed consent for BoNT treatment, as well as video documentation, where appropriate.


Five patients suffering from EPC were observed (Tables 1 and 2). All were treated with BoNT, receiving 2 injections at least. Before BoNT treatment, all had permanent myoclonic muscle activity, affecting one side of the face including platysma (2 patients), one side of the face plus ipsilateral arm (1 patient), one arm (1 patient), and one side of the face including platysma plus both arms (1 patient), respectively. For clinical presentation of patients 3 and 4, please consider the videos provided. In all cases, EPC was considered resistant to adequate trials of two tolerated, appropriately chosen, and used AED schedules.[18] Etiologies were RE in 3, unspecified focal brain inflammation in 1, and unknown in 1 patient, respectively, with disease onset ranging from 8 to 62 years. Duration of EPC at the time of first BoNT treatment varied between 1.5 and 16 years.

Table 1. Patient's characteristics and antiepileptic and immunotherapeutic regime before BoNT
Patient Sex and Age (Years) Age at Onset of EPC (Years) Etiology of EPC Location of EPC AED Before BoNT Immunotherapy Before BoNT

1lev, levetiracetame; pb, phenobarbital; tpm, topiramate; pht, phenytoin; ltg, lamotrigine; zsd, zonisamide; prb, pregabaline; oxc, oxcarbazepin; prd, primidone; slt, sultiame; esl, eslicarbazepine; cbz, carbamazepine; lcm, lacosamide; vpa, valproate; clon, clonazepame; MTX, methotrexate; IVIG, intravenous immunoglobuline.

1 Female, 27 8 RE Right face, right upper arm, right forearm ZSD, PRB, PRD, LEV, PB Dexamethasone, azathioprine, IVIG, plasma exchange, natalizumab
2 Male, 24 9 RE Right face, right platysma LTG, LEV, PHT, PB, ZSD, VPA, PRM, OXC, SLT Prednisone, IV steroids, mycofenolate mofetil, azathioprine
3 (Videos 1 and 2) Female, 27 22 Focal encephalitis Left shoulder, left forearm OXC, LEV MTX, prednisone, IV steroids, mycofenolate mofetil
4 (Videos 2–4) Male, 60 51 RE Left face, platysma OXC, ESL, LEV, PB, PHT, LTG, CBZ, TPM, ZSD, LCM, clon IVIG every 3 months
5 Female, 66 62 Unknown Left face and platysma, both shoulders, both forearms LEV, PB, LTG, CBZ, VPA, PHT, TPM IV steroids, prednisone, IVIG, plasma exchange
Table 2. BoNT treatment protocols and UMRS before and after BoNT treatment
Patient Treatment during BoNT Duration of EPC at Initiation of BoNT Treatment (Years) Latest BoNT Treatment Number of BoNT Treatments EPC Before BoNT Treatment (UMRS) EPC After Last BoNT Treatment (UMRS)

1lev, levetiracetame; pb, phenobarbital; tpm, topiramate; pht, phenytoin; ltg, lamotrigine; zsd, zonisamide; prb, pregabaline; oxc, oxcarbazepin; vpa, valproate, clbz, clobazame; IVIG, intravenous immunoglobuline.

1 LEV, PRB, natalizumab 15


face 14 units, arm 64 units: biceps brachii (12), brachioradialis (20), flexor dig. superficialis (24), flexor policis longus (8)

3 Face at rest: 9; face with action: 16; upper extremity at rest: 6; upper extremity with action: 12 Face at rest: 2; face with action: 4; upper extremity at rest: 2; upper extremity with action: 4


face and platysma 140 units

3 Face at rest: 8; face with action: 16 Face at rest: 0; face with action: 4
3 (Videos 1 and 2) OXC, LEV 1,5


arm 80 units: extensor dig. communis (16), extensor carpi radialis (12), extensor carpi ulnaris (12), flexor carpi radialis (8), flexor carpi ulnaris (8), trapezius (12), levator scapulae (12)

8 Upper extremity at rest: 12; upper extremity with action: 16 Upper extremity at rest: 0; upper extremity with action: 6
4 (Videos 2–4) LEV, PB, PHT, IVIG 5


face and platysma 84 units

12 Face at rest: 12; face with action: 16 Face at rest: 0; face with action: 4
5 LEV, PB, TPM, clbz 1.5


face and platysma 48 units, left arm 84 units: levator scapulae (12), flexor carpi radialis (12), pectoralis major (20), triceps brachii (20), flexor dig. superficialis (20), right arm: 24 units levator scapulae (16), flexor carpi radialis (8)

2 Face at rest: 6; face with action: 9; right upper extremity at rest: 4; right upper extremity with action: 6; left upper extremity at rest: 6; left upper extremity with action: 8 Face at rest: 0; face with action: 2; right upper extremity at rest: 0; right upper extremity with action: 1; left upper extremity at rest: 2; left upper extremity with action: 2

All BoNT preparations of serotype A marketed in Germany were used, of standard dilution (2.5 mL of saline for 100 units of onabotulinumtoxinA and incobotulinumtoxinA or 500 units of abobotulinumtoxinA, respectively). BoNT dosages were chosen in accord to treatment of hemifacial spasm as well as dystonia of the upper extremity. Injections were controlled clinically and with needle electromyography in some muscles of the upper extremity. Treatment intervals ranged from 11 to 13 weeks.

Before treatment, severity of myoclonus was high in all patients, pronounced with action, and average UMRS scores ranged from 8.0 (upper extremity at rest) to 14.25 (face with action; Table 3). BoNT treatment substantially reduced frequency and amplitude of myoclonus in all patients. Treatment effects were noted after the first application in every case. Follow-up was 6 months (two treatment cycles) to 4 years (12 treatment cycles) and demonstrated an ongoing improvement of EPC after every BoNT treatment in all 5 patients. The strongest average abatement of EPC after the latest BoNT treatment documented here was achieved for facial myoclonus at rest (94%), whereas myoclonus of upper extremities with action still showed a two-thirds reduction (Table 3). Also, BoNT had positive effects on functioning of affected body parts and led to pronounced improvement of speech, swallowing, and arm utilization. For treatment effects in patients 3 and 4, please consider the videos provided.

Table 3. Average improvement of EPC owing to BoNT treatment
EPC Location UMRS Sub-scores Reduction of Myoclonus (%)
Before BoNT After BoNT

1For UMRS, range 0 to 16; a higher value indicates a more severe myoclonus. UMRS values are averages for 4 patients with facial myoclonus and 3 with brachial myoclonus, respectively.

Face at rest n = 4 8.75 0.5 94
Face with action 14.25 3.5 75
Arm at rest n = 3 8.0 1.4 82
Arm with action 12.0 4.0 67

In all patients, BoNT treatment ameliorated EPC significantly, regardless of patient age, EPC etiology, disease duration, or concomitant medication. There were no adverse events. After initiation of BoNT, AEDs were unchanged in all patients during the study period. Also, no additional EEG data were obtained during the BoNT treatment period. Immunosuppressive treatments were modified only once (in patient 3). Here, prednisone and methotrexate were discontinued owing to a favorable clinical course. At the end of the observation period, 2 patients (patients 3 and 4) continued BoNT treatment and 2 were lost to follow up (patients 2 and 5). In patient 1, after three applications of BoNT, EPC abated, probably owing to treatment with natalizumab, which was initiated 9 months before BoNT. This patient was also reported elsewhere.[19]


In our case series, all patients demonstrated a substantial improvement of EPC as a result of BoNT treatment. Beside reduction of frequency and amplitude of myoclonus, a considerable gain of function was achieved, with improvement of speech, swallowing, and grasping of objects, respectively (also see supporting video material). Amelioration started after the first application and was ongoing, addressing the need for a long-lasting therapeutic option in EPC.

Primarily, reduction of myoclonus may result from local muscle paralysis. However, besides attenuation of amplitude, we noted a distinct effect on myoclonus frequency, hinting at central mechanisms of BoNT treatment. Similar observations were made in spasticity after stroke, in which administration of BoNT modulated and improved abnormal central reorganization (maladaptive plasticity), as measured with transcranial magnetic stimulation and peripheral nerve excitability studies.[12] Also, in dystonia, functional imaging studies delivered ample evidence for a modulation of basal ganglia/thalamocortical loops facilitating dystonic movements owing to BoNT treatment.[20]Similar cortical/subcortical mechanisms are discussed in the abnormal excitation maintaining EPC,[5, 21] and their modulation might participate in the excellent treatment effects observed in our patients. Notably, in tremors—which result, presumably, from a pathophysiology distinct from EPC—administration of BoNT had no effect on tremor frequency (however, observed here in EPC), burst duration, or interburst intervals, whereas tremor amplitude was attenuated similarly.[22] However, whether BoNT therapy exerts an effect on EEG activity remains unclear, given that we did not obtain EEG data after initiation of BoNT treatment.

Whereas three single-patient studies observed similar effects of BoNT treatment in EPC,[14-16] Tarsy and Schachter reported on two treatment failures in brachial EPC in 1995.[13] Eventually, this discrepancy might be explained by a more focused injection protocol with treatment of only two and five muscles, respectively, in contrast to a more widespread distribution of BoNT in four, five, and seven muscles injected here. Second, the short-termed applications with up to five treatment sessions over 8 weeks constitute a potential risk for BoNT treatment failure owing to formulation of neutralizing antibodies.[23]

EPC is a rare disorder, and our study's sample size limits the generalization of the observed effects. Although we used an established assessment scale, the rating of treatment effects was not blinded. Furthermore, although there was no additional immunosuppressive treatment after the initiation of BoNT, we cannot exclude completely that delayed effects of immunosuppression abated EPC. However, we observed a clinical improvement in all cases, after each injection, with onset after 4 to 8 days. Finally, 2 patients were lost to follow-up, in both cases because of a change of habitation.

Despite these limitations, we conclude that BoNT treatment is a safe, easily applicable, and valuable therapeutic option in patients suffering from medication-resistant EPC. Based on its immediate impact on activities of daily living, and with regard to the long-term efficacy in our patients, it should be considered as an early approach, instead of an “ultima-ratio” application, allowing prompt positive (add-on) effects.


Technical Considerations

For medicolegal purposes, before videotaping a patient exam, written informed consent must be obtained from the patient.[6] The physician should keep this consent together with all other medical documents. We find it preferable to videotape the signed consent form so that it is located directly with the patient's examination on the same video. Written informed consent is also important for facilitating sharing of the videotape with other providers, if needed. All relevant documents should be videotaped, such as the Montreal Cognitive Assessment, handwriting, and Archimedes spiral drawing, given that these tests frequently add valuable information regarding the diagnosis. Ideally, the videotape should be systematic and follow a consistent pattern. Though every physician will have his own style of examining the patient, we have found it works best to first videotape the patient while sitting, and then proceed in the examination in a rostral-caudal sequence, comparing the two sides after each exam maneuver. This is followed by having the patient arise from a sitting to a standing position (initially without pushing off, if the patient is able, and then pushing off with his or her hands if the patient fails to arise initially). The patient is then asked to walk for at least 5 meters in each direction in an unimpeded corridor with at least two turns to assess gait and turning. Walking is best observed by videotaping the patient walking away from and toward the camera, such that both arms and legs are visible at all times, rather than in a plane 90 degrees from the camera, from which one cannot observe the two sides of the patient's body at the same time. Postural reflexes are assessed with the pull test, which is often abnormal in classical parkinsonism, but may also be helpful in distinguishing between other movement disorders. For example, patients with Huntington's disease, dopa-responsive dystonia, and MSA frequently have positive pull tests, in contrast to patients with other forms of chorea, dystonia, and cerebellar ataxia, which do not affect postural stability. During the pull test or gait assessment, posture may be recorded as well. After these standing procedures, it is useful to observe the patient in the act of sitting down. This concludes the standard videotape. If clinically indicated, additional videotaping can be done to demonstrate the effect of postures or positions (e.g., lying supine) or specific tasks such as writing, talking, singing, biting, chewing, swallowing, drinking, holding objects, pouring water into a cup, running, tandem walking, walking backward, or standing on one leg.

In almost all circumstances, the videotape can be performed with the patient fully clothed. In specific cases, it may be necessary to remove specific items of clothing obstructing anatomical locations of interest, as in, for example, foot dystonia or spinal myoclonus. The videotape is not uniform for all patients, although the general guidelines do apply to all cases. Different symptoms require focusing on specific tasks.

While videotaping a patient, the camera should be placed directly in front of the patient (rather than off to one side) in order to observe for asymmetries between the two sides of the body. Any objects impairing the camera's view should be removed and care should be taken to avoid videotaping bystanders or family and friends accompanying the patient. The room should be well lit and be large enough to include the patient's entire body within the camera screen. Avoid backlighting by not aiming the camera toward windows or lamps. The background noise (air conditioners and fans) should be minimized in order not to miss relevant clinical signs, such as slurred speech or voice tremor. The photographer should alternately zoom in on the area of interest being examined and zoom out to show the whole body during motor activation. This can sometimes enhance involuntary movements in other parts of the body,[7, 8] or cause the disappearance of movements by distraction as occasionally observed in patients with psychogenic movement disorders.[9] The patient should sit with arms and legs uncrossed (hands in lap). The camera battery should be fully charged before beginning to videotape in order to maintain continuity of the exam. We recommend videotaping the patient at the first clinic visit in order to have a baseline audiovisual record with which to compare future clinical evaluations. Preferably, the camera operator is not simultaneously examining the patient given that some features of the exam may not be videotaped by the examiner. In the remainder of this article, we offer specific recommendations for videotaping an examination tailored to several common movement disorders.


  1. Cranial evaluation: Videotape the eyes by zooming in, assessing for square wave jerks, ocular movements, and apraxia of eyelid opening. Videotape the patient speaking to assess for dysarthria and prosody of speech as well as voice amplitude. Videotape the examination of frontal release signs (glabellar, snout, and palmomental signs). While examining for palmomental reflexes, videotape both the hand and face simultaneously (see Videos 1 and 2).
  2. When examining hands for re-emergent tremor, make sure to videotape the hands for at least 15 seconds since this tremor does not appear immediately.[10]
  3. During the pull test, the patient should stand sideways (profile view) relative to the camera. The patient's entire body from head to toe should be viewable so that both the upper and lower body can be observed.
  4. Handwriting should be videotaped. It is recommended that the patient write in print as well as script, and write a sentence a minimum of three times, each below the previous one, in order to assess for micrographia and decrement in script size.[11]
  5. Dyskinesias are often enhanced by motor activation including speaking. While examining head or limb movement, be sure to videotape the entire body.


  1. When videotaping a patient with cervical dystonia, be sure to include the primary head position and range of neck movement. In addition, videotape the involved muscles which may be hypertrophied. Always ask the patient to lean the back of his or her head against the wall, and videotape any effect on dystonic posture. Have the patient slowly move his or her head in all directions, looking for both null and activating positions. With the head away from the wall, instruct the patient to close his eyes and relax and let the head move by itself if it wants to drift.
  2. For task-specific writer's cramp, include the entire arm in the video, not just the hand. Place the camera so that it is aligned with the patient's forearm. This provides the best view to observe abnormal movements of the forearm. Writing with each hand should be tested. At times during writing, have the camera focus on the nonwriting hand, looking for mirror movements.
  3. Videotape handwriting and penmanship even if the patient presents with dystonia in other parts of the body (such as the neck or face) given that the hand is occasionally involved as well.
  4. Be sure to remove clothing when videotaping truncal or foot dystonia.
  5. If dystonia is observed in any body part, videotape the presence of sensory tricks (gestes antagoniste) and also the testing for null positions.

Essential Tremor

  1. Handwriting should be videotaped because this can demonstrate the impact of tremor on writing and also help differentiate between PD (micrographia) and essential tremor (macrographia).[12] Archimedes spiral drawing is routinely used to evaluate tremor and should be videotaped in all patients.
  2. The patient should be videotaped with hands at rest, assuming a posture, and with action. Postural tremor should be videotaped with the arms stretched in front of the body and in the wing position as well. When videotaping the finger-to-nose test, have the camera directly in front of the outstretched arm rather than at a side view.
  3. Specific tasks meant to elicit tremor, such as eating with a spoon, pouring liquid from one glass to another, or pointing to a target with a laser pointer, may be useful in the examination and should be recorded.
  4. Finger-to-nose testing can be cumbersome if the camera operator is also the examiner. In this case, an alternate far target, such as a pen held by the examiner, may be used to extend the distance between the camera and the patient.

Tourette's and Tic Disorders

  1. Tics are intermittent in nature, and many patients display fewer in the doctor's office. Therefore, it is important to have the camera running at all times. Once video consent is obtained, set the camera on the desk focused on the patient while the physician is conducting the interview and examining the patient. This extra footage may pick up tics that are not observed otherwise, and noninformative footage may be edited out later. If tics are not observed during the interview or formal examination, leave the camera on the desk running while the examiner excuses him- or herself and leaves the room for at least 5 minutes. Often, after the examiner is out of the room, the tics emerge.
  2. Because the body part(s) involved in tic disorders may not be immediately apparent to the patient or physician, it is important that the patient's entire body be included in the video. When the location of the tics is identified, close-ups of these areas can be obtained.
  3. Patients should be observed for tics when: speaking, sitting quietly, performing a cognitive task, and walking. During this portion of the examination, they should be instructed to feel free to tic as much or as little as needed. In order to demonstrate the voluntary suppressibility and subsequent rebound of tics, patients should be asked to refrain from exhibiting any motor and vocal tics for a period of at least 30 seconds and then allowed to tic freely.
  4. To adequately capture vocal tics, which may be low-volume sniffing or throat clearing, ensure that the camera's microphone is close enough to the patient and of high enough quality to record these sounds.


Videotaping the neurological examination is a valuable diagnostic, educational, and research tool and is especially important in the field of movement disorders, which relies heavily on critical observation of phenomenology. Many videotapes suffer from poor attention to technical issues, which can detract from the quality of the video both by obscuring as well as failing to highlight important clinical information. We hope that the tips for producing an effective video that we have outlined above will serve as a useful guide for clinicians, students, and educators and enhance the effectiveness of the videotaped patient encounter for diverse purposes.



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