- Email: [email protected]
“I feel my arm shaking”: partial cataplexy mistaken for drug-resistant focal epilepsy
Accepted Manuscript "I feel my arm shaking": Partial cataplexy mistaken for drug-resistant focal epilepsy Vera Dinkelacker, MD, PhD, Vi-Huong Nguyen-Michel, MD, Lionel Thivard, MD, PhD, Vincent Navarro, MD, PhD, Claude Adam, MD, PhD, Olivier Pallanca, MD, Isabelle Arnulf, MD, PhD PII:
S1389-9457(17)30206-X
DOI:
10.1016/j.sleep.2017.05.003
Reference:
SLEEP 3390
To appear in:
Sleep Medicine
Received Date: 23 February 2017 Revised Date:
29 April 2017
Accepted Date: 3 May 2017
Please cite this article as: Dinkelacker V, Nguyen-Michel V-H, Thivard L, Navarro V, Adam C, Pallanca O, Arnulf I, "I feel my arm shaking": Partial cataplexy mistaken for drug-resistant focal epilepsy, Sleep Medicine (2017), doi: 10.1016/j.sleep.2017.05.003. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT "I feel my arm shaking": Partial cataplexy mistaken for drug-resistant focal epilepsy
Vera Dinkelacker, MD, PhD (1,2,3), Vi-Huong Nguyen-Michel, MD (1), Lionel Thivard, MD, PhD (1,2), Vincent Navarro, MD, PhD (1,2), Claude Adam, MD, PhD (1), Olivier
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Pallanca, MD (4), Isabelle Arnulf, MD,PhD (4) 1: Epileptology Unit, Department of Neurology, Pitié-Salpêtrière Hospital, Paris, France 2: Brain and Spine Institute (ICM), Paris, France
3: Rothschild Foundation, Neurology Department, Paris, France
Title character count: 85 characters
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4: Sleep Disorders Unit, National Reference Center for Narcolepsy, Hypersomnia and Kleine-Levin syndrome, Pitié-Salpêtrière Hospital, Paris, France
Number of words in the body of the manuscript: 746 excluding acknowledgements Number of figures: 1 Number of tables: 1
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Number of videos: 2
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Number of references: 10
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Corresponding author:
Vera Dinkelacker, MD-PhD, Rothschild Foundation, Neurology Department, 25 Rue Manin, 75019 Paris
Tel: +33 1 48 03 65 97 Fax: +33 1 48 03 65 90 E mail : [email protected] Search terms: Narcolepsy, Partial Cataplexy, Focal Epilepsy, Atonia, EEG
1
ACCEPTED MANUSCRIPT "I feel my arm shaking": Partial cataplexy mistaken for drug-resistant focal epilepsy
Introduction There is often a considerable delay in the diagnosis of narcolepsy1,2. This is partly due to the
RI PT
insidious nature of disease onset and incomplete presence of characteristic symptoms2. Moreover, narcolepsy may mimic other neurological diseases (in particular, epilepsy) due to
SC
the presence of paroxysmal events3. Epilepsy, which is much more prevalent, might thus appear as a straightforward diagnosis, especially if the symptoms are focal and associated
M AN U
with abnormal movements or jerks.
Here we report a case of a 24-year-old man, who complained of recurrent episodes of "shaking" of his right arm and was erroneously treated for epilepsy for two years. Videoelectroencephalogram (EEG) monitoring during cataplectic attacks helped to unravel the
EP
Case description
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misleading features of segmental cataplexy.
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A 24-year-old man without remarkable medical history started to have transient spells in the course of stressful life events. These spells, which he himself described as "shaking of his right arm," were associated with the inability to speak and rarely affected the legs, causing a fall. He was unsuccessfully treated with four anti-epileptic drugs for suspected focal seizures. Among these, Gabapentin was tapered after an episode of daytime visual hallucinations: the patient saw the socket of his room on fire4. Valproic acid caused/contributed to a weight gain of 35kg/70lb and significant tiredness. The pharmacoresistance and psychological context incited his epileptologist to refer him to video-EEG 2
ACCEPTED MANUSCRIPT monitoring, which allowed the correct classification of these shaking events as partial cataplexy (Fig_1, recordings performed according to local ethics guidelines). The sleep study confirmed the diagnosis with five out of five sleep-onset rapid-eye-
RI PT
movement sleep (REM) periods. A mean sleep latency of 1.4 min and an Epworth score of 16 revealed an excessive daytime somnolence, despite there being no spontaneous clinical complaint. Furthermore, polysomnography evidenced major sleep fragmentation and REM
SC
sleep without atonia. HLA DQB1*0602 was positive. Tapering of valproic acid allowed for a significant weight loss (30kg/60lb). The patient became symptom free with modafinil and
M AN U
venlafaxine. He has not complained of somnolence or cataplectic attacks for two years. Video Analysis
Video-EEG-monitoring documented two episodes of several minutes duration without
TE D
specific prodromes. The patient presented with head drop, weakness of upper limbs and facial muscles resulting in eyelid closure and slurred speech with preserved consciousness (Video_1); the latter was confirmed by clinical examination (supplementary videos). When
EP
he attempted to move, instability of muscle tone generated shaking movements of the right
AC C
upper limb, similar to negative myoclonus (Video_2). Subjectively, episodes started with a feeling of “tremor,” not necessarily visible, of parts of his muscles and limbs, which otherwise felt “heavy.” EEG recordings did not show any epileptic discharge, but captured significant changes in electromyogram (EMG) artifacts of facial muscles. EMG-amplitude increased, showed a ragged appearance and was intermittently interrupted for several seconds during prolonged atonia. Facial EMG thus demonstrated instability of muscle tone on a short and longer time scale. The episodes lasted 3 - 4 minutes without loss of consciousness, confusion or amnesia. 3
ACCEPTED MANUSCRIPT
Discussion This case graphically illustrates the diagnostic pitfalls of narcolepsy, which some authors
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claim to be a master of disguise.2 Beyond the misleading psychological context5, the present case was particularly challenging due to the manifest segmental symptoms of partial cataplexy. Similarities between narcolepsy and epilepsy have been discussed since Gelineau
SC
in 1880.3 With the exception of one case description in children,6 the medical literature largely represents the differential diagnosis between narcolepsy and generalized epilepsy.3,7
M AN U
In our patient, though, it is specifically the focal nature of symptoms which entailed two years of ineffective treatment. Some further elements puzzled the physicians: slurred speech emanating from facial weakness, mistaken for epileptic speech arrest, the prolonged duration of the episodes without immediate falls whereas emerging sleepiness
TE D
and weight gain were considered as an adverse effect of valproic acid. Video-EEG monitoring documented intermittent segmental atonia resulting in visible
EP
“shaking,” equivalent to negative myoclonus,3,8 and in prolonged atonic spells with head
AC C
drop.9 In congruence with the study by Vetrugno and colleagues,10 the EMG signature of narcolepsy spanned very brief events, in the millisecond range, to several seconds of atonia. We propose that the subjective feeling of “tremor” corresponds to sustained episodes of intermittent milliseconds interruptions of muscle tone. Our report on misleading focal motor symptoms completes the current literature, which so far focuses on the differential diagnosis with suspected generalized epilepsy.3,7, indicating that partial cataplexy, as a prevalent hallmark of narcolepsy type 1,9,10 may still be less wellknown in the neurological community.2 Thorough characterization of segmental atonia with 4
ACCEPTED MANUSCRIPT video and neurophysiological monitoring may therefore help to overcome the diagnostic challenges of partial cataplexy.
Acknowledgements:
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We thank Corinne Lachaux and Joseph Barba for expert technical assistance.
SC
References:
1. Frauscher, B. et al. Delayed diagnosis, range of severity, and multiple sleep comorbidities: a
M AN U
clinical and polysomnographic analysis of 100 patients of the innsbruck narcolepsy cohort. J. Clin. Sleep Med. JCSM Off. Publ. Am. Acad. Sleep Med. 9, 805–812 (2013). 2. Mohsenin, V. Narcolepsy--master of disguise: evidence-based recommendations for management. Postgrad. Med. 121, 99–104 (2009).
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3. Zeman, A., Douglas, N. & Aylward, R. Lesson of the week: Narcolepsy mistaken for epilepsy. BMJ 322, 216–218 (2001).
4. Leu-Semenescu, S. et al. Hallucinations in narcolepsy with and without cataplexy: contrasts with Parkinson’s disease. Sleep Med. 12, 497–504 (2011).
(1994).
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5. Orellana, C. et al. Life events in the year preceding the onset of narcolepsy. Sleep 17, S50-53
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6. Macleod, S., Ferrie, C. & Zuberi, S. M. Symptoms of narcolepsy in children misinterpreted as epilepsy. Epileptic Disord. Int. Epilepsy J. Videotape 7, 13–17 (2005). 7. Fejerman, N. Nonepileptic disorders imitating generalized idiopathic epilepsies. Epilepsia 46 Suppl 9, 80–83 (2005).
8. Overeem, S. et al. The clinical features of cataplexy: a questionnaire study in narcolepsy patients with and without hypocretin-1 deficiency. Sleep Med. 12, 12–18 (2011). 9. Mattarozzi, K. et al. Clinical, behavioural and polysomnographic correlates of cataplexy in patients with narcolepsy/cataplexy. Sleep Med. 9, 425–433 (2008).
5
ACCEPTED MANUSCRIPT 10. Vetrugno, R. et al. Behavioural and neurophysiological correlates of human cataplexy: a video-
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SC
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polygraphic study. Clin. Neurophysiol. Off. J. Int. Fed. Clin. Neurophysiol. 121, 153–162 (2010).
6
ACCEPTED MANUSCRIPT Figure Legends: Figure 1: "Shaking" without epileptic activity on EEG (A) Muscle artifacts before the "seizure" (supplementary Video_1), soon followed by
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onset of cataplexy (Video_1). (B) "Shaking" of the right arm equivalent to negative myoclonus of upper limbs and head during partial cataplexy, with intermittently
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artifacts (suppl. Video_3), without epileptic activity.
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abolished muscle activity (Video_2). (C) Prolonged atonia with abolished muscle
7
ACCEPTED MANUSCRIPT Video Description: Video_1 and Video_2 (with supplementary videos 3 – 6): First episode with sudden onset muscle weakness, dropping of his book, head drop,
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difficulty to use the push button, upper limb "shaking", eyelid weakness and slurred speech as well as diminished strength on physical examination. Once recovered, the
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patient describes his subjective feeling of "shaking" (French with English subtitles).
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Video_1: Dinkelacker_1 onset push button
At "seizure onset", the patient experiences a subjective feeling of tremor and an
EP
objective head drop and weakness of upper limbs. He is conscious and attempts to catch the push button, which he finally succeeds to press, in order to alert the staff that
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he feels one of his spells. Contrary to a complex partial seizure, he has no epileptic aura, and no partial or complete loss of consciousness.
8
ACCEPTED MANUSCRIPT Video_2: Dinkelacker_2 shaking upper limb head drop During voluntary movements, the instability of muscle tone generated shaking movements of the right upper limb by intermittent atonia of the right upper limb,
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similar to negative myoclonus. Video concomitant to the EEG/EMG of Figure 1B, which is unremarkable for epileptic discharge.
Contrary to an epileptic motor seizure, the “jerks” are limited to voluntary movements
SC
and do not occur at rest. There is no initial tonic phase, no rhythmic jerks or cloni and
M AN U
no typical time course of a motor seizure with progressive waning of rhythmic jerks.
Supplementary Video_3: Dinkelacker_3 before the 'seizure'
Normal behavior of the patient, without upper limb or eyelid weakness, before the
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"seizure" onset. Video concomitant to the EEG/EMG of Figure 1A.
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Supplementary video_4: Dinkelacker_4 prolonged atonia Prolonged atonia with head drop and abolished muscle artifacts. Video concomitant to
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the EEG/EMG of Figure 1C, still without any epileptic discharge. Supplementary video_5: Dinkelacker_5 slurred speech eyelid and limb weakness Physical examination reveals slurred speech and confirming upper limb weakness. In contrast to supplementary video_3, the patient now shows clear eyelid weakness and cataplectic facies when communicating.
9
ACCEPTED MANUSCRIPT Supplementary video_6: Dinkelacker_6 I feel it shaking The patient explains his subjective feeling of shaking of parts of his muscles.
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Supplementary videos 7 and 8:
Second episode with sudden onset muscle weakness, head drop, eyelid weakness, and
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during physical examination, slurred speech and impossibility to raise his arms while "shaking". Once recovered, the patient is able to raise upper limbs and to correctly
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EP
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name the hospital (French with English subtitles).
Supplementary video_7: Dinkelacker_7 slurred speech arm shaking In this second episode, the patient presents with slurred speech and 'arm shaking similar to Video_2. Clinical examination confirms initially incomprehensible speech and prolonged upper limb weakness when raising his arms.
10
ACCEPTED MANUSCRIPT Supplementary video_8: Dinkelacker_8 upper limbs recovered Clinical examination during the ending of the episode allows assessing that the patient
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has recovered, both for speech and for upper limb weakness.
11
ACCEPTED MANUSCRIPT Atonic seizures in focal epilepsy
Atonic seizures in symptomatic generalized epilepsy
Myoclonic seizures in idiopathic generalized epilepsy
Age of onset
Variable, Generally 2nd or 3rd decade1
Variable, more frequent in adulthood
Severe childhood epilepsies, onset often 2 - 6 years2
Variable, onset peaks in adolescence3
Associated symptoms
Somnolence Sleep paralysis Hallucinations Sleep fragmentation
Focal seizures of location related semiology, +/- secondarily generalized seizures
Mental retardation Variety of seizures (+ myoclonic in Doose's, + tonic in Lennox-Gastaut)
Immediate triggers of the attack
Frequent: laughing, joking, surprise, tiredness
Usually absent (exceptionally reflex epilepsies)
Usually absent (rare reflex epilepsies)
Infrequent (photic stimulation, awakening)
Prodrome to the onset of the attack
Absent
Exceptional in atonic seizures, in focal seizures aura indicative of onset zone
Usually absent
Usually absent
Attack onset
Abrupt
Abrupt, may occur during a seizure with focal onset
Abrupt
Abrupt
Consciousness
Present
Most often absent in atonic seizures
Most often absent (unresponsiveness)
Most often present
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EP
AC C
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Cataplexy in NT1
Generalized seizures (tonic-clonic), absences seizures
Language
Absent or slurred
Absent, speech arrest in prolonged focal seizures
Absent
Can be preserved
Eyes
Eyelid weakness
Variable, fixed gaze if prolonged partial seizure
Variable, half closed
Variable, possible eyelid myoclonia
Facial muscle tonus
Atonic, cataplectic facies, jaw tremor
Atonic
Atonic
Possible facial myoclonus
ACCEPTED MANUSCRIPT Partially or globally affected, atonic falls
Atonic predominant on the limbs
Atonic predominant on the trunk
Present, positive myoclonus predominant on the upper limbs
Myoclonus
Absent during daytime (except for "negative myoclonus" during attacks)
Exceptionally present (epilepsia partialis continua)
Can be associated (myoclonic-astatic seizures)
Present, often affecting upper limbs or eye lids
Duration
Seconds, rarely minutes
Seconds, associated focal seizures often last minutes
Seconds
Postictal confusion
Absent
Can be present
Can be present
Ictal/postictal amnesia
Absent
Usually present
Deep tendon reflexes
Absent
EEG findings
Unremarkable (wake)
EMG findings
Abolition of postural muscle tone
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Bilateral synchrony
Usually present
?
Seconds
Absent Usually absent
(rather enhanced)4
Irregular spike and wave discharge < 3Hz
Polyspike waves
Abolition of muscle tone
Abolition of muscle tone
Myoclonus, burst of EMG activity < 500ms (cortical often < 100ms)5
Possible activation of spike waves during sleep
Possible activation of spike waves or tonic seizures during sleep
Possible activation of spike and polyspike waves during sleep
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PSG findings
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Body muscle tonus
Table 1: Characteristics of atonic attacks in NT1, partial and generalized epilepsy Synopsis of atonic attacks in narcolepsy type 1 (NT1) and different forms of epilepsy. While drop attacks in epilepsy can be of multiples origins (myoclonic or tonic seizures, asystole, etc.), genuine atonic seizures are very rare in focal epilepsy (bilateral
ACCEPTED MANUSCRIPT synchrony) and generally limited to severe childhood epilepsy in generalized forms of the disease (Doose and Lennox-Gastaut syndrome, rare forms of childhood epilepsy).
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See supplementary table for complete reference.1–11
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ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT "I feel my arm shaking": Partial cataplexy mistaken for drug-resistant focal epilepsy
•
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Highlights:
Narcolepsy type 1 (NT1) may mimic epilepsy due to the presence of paroxysmal events
We present a case of a young man who received antiepileptic medication for 2
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•
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years •
Partial attacks presented with "shaking of the upper limb" and "speech arrest"
•
Video-EEG monitoring revealed intermittent atonia, similar to negative myoclonus
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Partial cataplexy may thus be misinterpreted as focal epilepsy
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•
1
S1389-9457(17)30206-X
DOI:
10.1016/j.sleep.2017.05.003
Reference:
SLEEP 3390
To appear in:
Sleep Medicine
Received Date: 23 February 2017 Revised Date:
29 April 2017
Accepted Date: 3 May 2017
Please cite this article as: Dinkelacker V, Nguyen-Michel V-H, Thivard L, Navarro V, Adam C, Pallanca O, Arnulf I, "I feel my arm shaking": Partial cataplexy mistaken for drug-resistant focal epilepsy, Sleep Medicine (2017), doi: 10.1016/j.sleep.2017.05.003. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT "I feel my arm shaking": Partial cataplexy mistaken for drug-resistant focal epilepsy
Vera Dinkelacker, MD, PhD (1,2,3), Vi-Huong Nguyen-Michel, MD (1), Lionel Thivard, MD, PhD (1,2), Vincent Navarro, MD, PhD (1,2), Claude Adam, MD, PhD (1), Olivier
RI PT
Pallanca, MD (4), Isabelle Arnulf, MD,PhD (4) 1: Epileptology Unit, Department of Neurology, Pitié-Salpêtrière Hospital, Paris, France 2: Brain and Spine Institute (ICM), Paris, France
3: Rothschild Foundation, Neurology Department, Paris, France
Title character count: 85 characters
M AN U
SC
4: Sleep Disorders Unit, National Reference Center for Narcolepsy, Hypersomnia and Kleine-Levin syndrome, Pitié-Salpêtrière Hospital, Paris, France
Number of words in the body of the manuscript: 746 excluding acknowledgements Number of figures: 1 Number of tables: 1
EP
Number of videos: 2
TE D
Number of references: 10
AC C
Corresponding author:
Vera Dinkelacker, MD-PhD, Rothschild Foundation, Neurology Department, 25 Rue Manin, 75019 Paris
Tel: +33 1 48 03 65 97 Fax: +33 1 48 03 65 90 E mail : [email protected] Search terms: Narcolepsy, Partial Cataplexy, Focal Epilepsy, Atonia, EEG
1
ACCEPTED MANUSCRIPT "I feel my arm shaking": Partial cataplexy mistaken for drug-resistant focal epilepsy
Introduction There is often a considerable delay in the diagnosis of narcolepsy1,2. This is partly due to the
RI PT
insidious nature of disease onset and incomplete presence of characteristic symptoms2. Moreover, narcolepsy may mimic other neurological diseases (in particular, epilepsy) due to
SC
the presence of paroxysmal events3. Epilepsy, which is much more prevalent, might thus appear as a straightforward diagnosis, especially if the symptoms are focal and associated
M AN U
with abnormal movements or jerks.
Here we report a case of a 24-year-old man, who complained of recurrent episodes of "shaking" of his right arm and was erroneously treated for epilepsy for two years. Videoelectroencephalogram (EEG) monitoring during cataplectic attacks helped to unravel the
EP
Case description
TE D
misleading features of segmental cataplexy.
AC C
A 24-year-old man without remarkable medical history started to have transient spells in the course of stressful life events. These spells, which he himself described as "shaking of his right arm," were associated with the inability to speak and rarely affected the legs, causing a fall. He was unsuccessfully treated with four anti-epileptic drugs for suspected focal seizures. Among these, Gabapentin was tapered after an episode of daytime visual hallucinations: the patient saw the socket of his room on fire4. Valproic acid caused/contributed to a weight gain of 35kg/70lb and significant tiredness. The pharmacoresistance and psychological context incited his epileptologist to refer him to video-EEG 2
ACCEPTED MANUSCRIPT monitoring, which allowed the correct classification of these shaking events as partial cataplexy (Fig_1, recordings performed according to local ethics guidelines). The sleep study confirmed the diagnosis with five out of five sleep-onset rapid-eye-
RI PT
movement sleep (REM) periods. A mean sleep latency of 1.4 min and an Epworth score of 16 revealed an excessive daytime somnolence, despite there being no spontaneous clinical complaint. Furthermore, polysomnography evidenced major sleep fragmentation and REM
SC
sleep without atonia. HLA DQB1*0602 was positive. Tapering of valproic acid allowed for a significant weight loss (30kg/60lb). The patient became symptom free with modafinil and
M AN U
venlafaxine. He has not complained of somnolence or cataplectic attacks for two years. Video Analysis
Video-EEG-monitoring documented two episodes of several minutes duration without
TE D
specific prodromes. The patient presented with head drop, weakness of upper limbs and facial muscles resulting in eyelid closure and slurred speech with preserved consciousness (Video_1); the latter was confirmed by clinical examination (supplementary videos). When
EP
he attempted to move, instability of muscle tone generated shaking movements of the right
AC C
upper limb, similar to negative myoclonus (Video_2). Subjectively, episodes started with a feeling of “tremor,” not necessarily visible, of parts of his muscles and limbs, which otherwise felt “heavy.” EEG recordings did not show any epileptic discharge, but captured significant changes in electromyogram (EMG) artifacts of facial muscles. EMG-amplitude increased, showed a ragged appearance and was intermittently interrupted for several seconds during prolonged atonia. Facial EMG thus demonstrated instability of muscle tone on a short and longer time scale. The episodes lasted 3 - 4 minutes without loss of consciousness, confusion or amnesia. 3
ACCEPTED MANUSCRIPT
Discussion This case graphically illustrates the diagnostic pitfalls of narcolepsy, which some authors
RI PT
claim to be a master of disguise.2 Beyond the misleading psychological context5, the present case was particularly challenging due to the manifest segmental symptoms of partial cataplexy. Similarities between narcolepsy and epilepsy have been discussed since Gelineau
SC
in 1880.3 With the exception of one case description in children,6 the medical literature largely represents the differential diagnosis between narcolepsy and generalized epilepsy.3,7
M AN U
In our patient, though, it is specifically the focal nature of symptoms which entailed two years of ineffective treatment. Some further elements puzzled the physicians: slurred speech emanating from facial weakness, mistaken for epileptic speech arrest, the prolonged duration of the episodes without immediate falls whereas emerging sleepiness
TE D
and weight gain were considered as an adverse effect of valproic acid. Video-EEG monitoring documented intermittent segmental atonia resulting in visible
EP
“shaking,” equivalent to negative myoclonus,3,8 and in prolonged atonic spells with head
AC C
drop.9 In congruence with the study by Vetrugno and colleagues,10 the EMG signature of narcolepsy spanned very brief events, in the millisecond range, to several seconds of atonia. We propose that the subjective feeling of “tremor” corresponds to sustained episodes of intermittent milliseconds interruptions of muscle tone. Our report on misleading focal motor symptoms completes the current literature, which so far focuses on the differential diagnosis with suspected generalized epilepsy.3,7, indicating that partial cataplexy, as a prevalent hallmark of narcolepsy type 1,9,10 may still be less wellknown in the neurological community.2 Thorough characterization of segmental atonia with 4
ACCEPTED MANUSCRIPT video and neurophysiological monitoring may therefore help to overcome the diagnostic challenges of partial cataplexy.
Acknowledgements:
RI PT
We thank Corinne Lachaux and Joseph Barba for expert technical assistance.
SC
References:
1. Frauscher, B. et al. Delayed diagnosis, range of severity, and multiple sleep comorbidities: a
M AN U
clinical and polysomnographic analysis of 100 patients of the innsbruck narcolepsy cohort. J. Clin. Sleep Med. JCSM Off. Publ. Am. Acad. Sleep Med. 9, 805–812 (2013). 2. Mohsenin, V. Narcolepsy--master of disguise: evidence-based recommendations for management. Postgrad. Med. 121, 99–104 (2009).
TE D
3. Zeman, A., Douglas, N. & Aylward, R. Lesson of the week: Narcolepsy mistaken for epilepsy. BMJ 322, 216–218 (2001).
4. Leu-Semenescu, S. et al. Hallucinations in narcolepsy with and without cataplexy: contrasts with Parkinson’s disease. Sleep Med. 12, 497–504 (2011).
(1994).
EP
5. Orellana, C. et al. Life events in the year preceding the onset of narcolepsy. Sleep 17, S50-53
AC C
6. Macleod, S., Ferrie, C. & Zuberi, S. M. Symptoms of narcolepsy in children misinterpreted as epilepsy. Epileptic Disord. Int. Epilepsy J. Videotape 7, 13–17 (2005). 7. Fejerman, N. Nonepileptic disorders imitating generalized idiopathic epilepsies. Epilepsia 46 Suppl 9, 80–83 (2005).
8. Overeem, S. et al. The clinical features of cataplexy: a questionnaire study in narcolepsy patients with and without hypocretin-1 deficiency. Sleep Med. 12, 12–18 (2011). 9. Mattarozzi, K. et al. Clinical, behavioural and polysomnographic correlates of cataplexy in patients with narcolepsy/cataplexy. Sleep Med. 9, 425–433 (2008).
5
ACCEPTED MANUSCRIPT 10. Vetrugno, R. et al. Behavioural and neurophysiological correlates of human cataplexy: a video-
AC C
EP
TE D
M AN U
SC
RI PT
polygraphic study. Clin. Neurophysiol. Off. J. Int. Fed. Clin. Neurophysiol. 121, 153–162 (2010).
6
ACCEPTED MANUSCRIPT Figure Legends: Figure 1: "Shaking" without epileptic activity on EEG (A) Muscle artifacts before the "seizure" (supplementary Video_1), soon followed by
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onset of cataplexy (Video_1). (B) "Shaking" of the right arm equivalent to negative myoclonus of upper limbs and head during partial cataplexy, with intermittently
AC C
EP
TE D
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artifacts (suppl. Video_3), without epileptic activity.
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abolished muscle activity (Video_2). (C) Prolonged atonia with abolished muscle
7
ACCEPTED MANUSCRIPT Video Description: Video_1 and Video_2 (with supplementary videos 3 – 6): First episode with sudden onset muscle weakness, dropping of his book, head drop,
RI PT
difficulty to use the push button, upper limb "shaking", eyelid weakness and slurred speech as well as diminished strength on physical examination. Once recovered, the
M AN U
SC
patient describes his subjective feeling of "shaking" (French with English subtitles).
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Video_1: Dinkelacker_1 onset push button
At "seizure onset", the patient experiences a subjective feeling of tremor and an
EP
objective head drop and weakness of upper limbs. He is conscious and attempts to catch the push button, which he finally succeeds to press, in order to alert the staff that
AC C
he feels one of his spells. Contrary to a complex partial seizure, he has no epileptic aura, and no partial or complete loss of consciousness.
8
ACCEPTED MANUSCRIPT Video_2: Dinkelacker_2 shaking upper limb head drop During voluntary movements, the instability of muscle tone generated shaking movements of the right upper limb by intermittent atonia of the right upper limb,
RI PT
similar to negative myoclonus. Video concomitant to the EEG/EMG of Figure 1B, which is unremarkable for epileptic discharge.
Contrary to an epileptic motor seizure, the “jerks” are limited to voluntary movements
SC
and do not occur at rest. There is no initial tonic phase, no rhythmic jerks or cloni and
M AN U
no typical time course of a motor seizure with progressive waning of rhythmic jerks.
Supplementary Video_3: Dinkelacker_3 before the 'seizure'
Normal behavior of the patient, without upper limb or eyelid weakness, before the
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"seizure" onset. Video concomitant to the EEG/EMG of Figure 1A.
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Supplementary video_4: Dinkelacker_4 prolonged atonia Prolonged atonia with head drop and abolished muscle artifacts. Video concomitant to
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the EEG/EMG of Figure 1C, still without any epileptic discharge. Supplementary video_5: Dinkelacker_5 slurred speech eyelid and limb weakness Physical examination reveals slurred speech and confirming upper limb weakness. In contrast to supplementary video_3, the patient now shows clear eyelid weakness and cataplectic facies when communicating.
9
ACCEPTED MANUSCRIPT Supplementary video_6: Dinkelacker_6 I feel it shaking The patient explains his subjective feeling of shaking of parts of his muscles.
RI PT
Supplementary videos 7 and 8:
Second episode with sudden onset muscle weakness, head drop, eyelid weakness, and
SC
during physical examination, slurred speech and impossibility to raise his arms while "shaking". Once recovered, the patient is able to raise upper limbs and to correctly
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EP
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name the hospital (French with English subtitles).
Supplementary video_7: Dinkelacker_7 slurred speech arm shaking In this second episode, the patient presents with slurred speech and 'arm shaking similar to Video_2. Clinical examination confirms initially incomprehensible speech and prolonged upper limb weakness when raising his arms.
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ACCEPTED MANUSCRIPT Supplementary video_8: Dinkelacker_8 upper limbs recovered Clinical examination during the ending of the episode allows assessing that the patient
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has recovered, both for speech and for upper limb weakness.
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ACCEPTED MANUSCRIPT Atonic seizures in focal epilepsy
Atonic seizures in symptomatic generalized epilepsy
Myoclonic seizures in idiopathic generalized epilepsy
Age of onset
Variable, Generally 2nd or 3rd decade1
Variable, more frequent in adulthood
Severe childhood epilepsies, onset often 2 - 6 years2
Variable, onset peaks in adolescence3
Associated symptoms
Somnolence Sleep paralysis Hallucinations Sleep fragmentation
Focal seizures of location related semiology, +/- secondarily generalized seizures
Mental retardation Variety of seizures (+ myoclonic in Doose's, + tonic in Lennox-Gastaut)
Immediate triggers of the attack
Frequent: laughing, joking, surprise, tiredness
Usually absent (exceptionally reflex epilepsies)
Usually absent (rare reflex epilepsies)
Infrequent (photic stimulation, awakening)
Prodrome to the onset of the attack
Absent
Exceptional in atonic seizures, in focal seizures aura indicative of onset zone
Usually absent
Usually absent
Attack onset
Abrupt
Abrupt, may occur during a seizure with focal onset
Abrupt
Abrupt
Consciousness
Present
Most often absent in atonic seizures
Most often absent (unresponsiveness)
Most often present
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Cataplexy in NT1
Generalized seizures (tonic-clonic), absences seizures
Language
Absent or slurred
Absent, speech arrest in prolonged focal seizures
Absent
Can be preserved
Eyes
Eyelid weakness
Variable, fixed gaze if prolonged partial seizure
Variable, half closed
Variable, possible eyelid myoclonia
Facial muscle tonus
Atonic, cataplectic facies, jaw tremor
Atonic
Atonic
Possible facial myoclonus
ACCEPTED MANUSCRIPT Partially or globally affected, atonic falls
Atonic predominant on the limbs
Atonic predominant on the trunk
Present, positive myoclonus predominant on the upper limbs
Myoclonus
Absent during daytime (except for "negative myoclonus" during attacks)
Exceptionally present (epilepsia partialis continua)
Can be associated (myoclonic-astatic seizures)
Present, often affecting upper limbs or eye lids
Duration
Seconds, rarely minutes
Seconds, associated focal seizures often last minutes
Seconds
Postictal confusion
Absent
Can be present
Can be present
Ictal/postictal amnesia
Absent
Usually present
Deep tendon reflexes
Absent
EEG findings
Unremarkable (wake)
EMG findings
Abolition of postural muscle tone
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Bilateral synchrony
Usually present
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Seconds
Absent Usually absent
(rather enhanced)4
Irregular spike and wave discharge < 3Hz
Polyspike waves
Abolition of muscle tone
Abolition of muscle tone
Myoclonus, burst of EMG activity < 500ms (cortical often < 100ms)5
Possible activation of spike waves during sleep
Possible activation of spike waves or tonic seizures during sleep
Possible activation of spike and polyspike waves during sleep
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PSG findings
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Body muscle tonus
Table 1: Characteristics of atonic attacks in NT1, partial and generalized epilepsy Synopsis of atonic attacks in narcolepsy type 1 (NT1) and different forms of epilepsy. While drop attacks in epilepsy can be of multiples origins (myoclonic or tonic seizures, asystole, etc.), genuine atonic seizures are very rare in focal epilepsy (bilateral
ACCEPTED MANUSCRIPT synchrony) and generally limited to severe childhood epilepsy in generalized forms of the disease (Doose and Lennox-Gastaut syndrome, rare forms of childhood epilepsy).
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See supplementary table for complete reference.1–11
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ACCEPTED MANUSCRIPT "I feel my arm shaking": Partial cataplexy mistaken for drug-resistant focal epilepsy
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Highlights:
Narcolepsy type 1 (NT1) may mimic epilepsy due to the presence of paroxysmal events
We present a case of a young man who received antiepileptic medication for 2
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Partial attacks presented with "shaking of the upper limb" and "speech arrest"
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Video-EEG monitoring revealed intermittent atonia, similar to negative myoclonus
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Partial cataplexy may thus be misinterpreted as focal epilepsy
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