Abstract
Background
In the sharp contrast with the existing literature, we frequently observe minipolymyoclonus, tremor and pseudodystonic thumb posturing in patients with motor neuron disease. We conducted a clinical and electrophysiological study to describe phenomenology, prevalence and pathophysiology of involuntary movements in motor neuron disease.
Methods
We included 77 consecutive patients. Involuntary movements were assessed at rest and on action. Patients were videotaped. Arm muscle tone, power and deep tendon reflexes were evaluated. Accelerometry with electromyography was recorded in a subset of patients.
Results
Involuntary movements were observed in 68.9% of patients and could be separated into rest minipolymyoclonus, thumb tremor, pseudodystonic thumb posture, action minipolymyoclonus, and action tremor. One-third of patients reported negative impact of involuntary movements on hand use. Logistic regression showed that rest minipolymyoclonus and thumb tremor were more likely to occur in patients with more prominent distal muscle weakness and less spasticity. Similarly, action involuntary movements were more likely to appear in weaker patients. Patients with brisk tendon reflexes were more likely to display action tremor than action minipolymyoclonus. Action tremor was characterized by accelerometer and corresponding electromyography peak frequency, which decreased with mass loading, suggesting a mechanical-reflex tremor.
Conclusions
Involuntary movements are common, but poorly recognized feature of motor neuron disease that may add to functional impairment. Results of our study suggest that involuntary movements are likely of peripheral origin, with a non-fused contraction of enlarged motor units being a common driving mechanism. Minipolymyoclonus appears if no synchronization of motor units occurs. When synchronization occurs via stretch reflex, mechanical-reflex tremor is generated.
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Supplementary file5 Video_1: Rest MPMC Video_1.1: MPMC seen in both thumbs, in the left 3rd and 4th finger and in the right index finger. Video_1.2: MPMC jerks affecting fingers bilaterally. Video_1.3: Occasional MPMC jerks affecting predominantly middle fingers on both sides. Left TT is also seen. Video_1.4: Continuous MPMC jerks affecting multiple fingers bilaterally. (MP4 58701 KB)
Supplementary file6 Video_2: Thumb tremor and pseudodystonic thumb posturing Video_2.1.1: Bilateral TT. Video_2.1.2: Bilateral pseudodystonic thumb posturing and TT. Video_2.1.3: Pseudodystonic posturing of right thumb with occasional bursts of TT. In the second half of the video, left TT is also seen. Video_2.1.4: Bilateral TT. Video_2.1.5: Bilateral TT that is clearly dependant on hand position. Video_2.1.6: Right TT and left pseudodystonic thumb posture. Video_2.1.7: Right pseudodystonic thumb posture and prominent left TT. Upon relaxation (patient’s hands are held by the examiner), TT and pseudodystonic posturing cease and only MPMC is occasionally appearing. Video_2.1.8: Pseudodystonic posturing of the right thumb can be seen, as well as initial movement bringing the thumb in abducted/extended position. When hand position is passively changed by the examiner, the thumb assumes flexed posture. Video_2.1.9: Pseudodystonic posture of left thumb, later replaced by TT. (MP4 133828 KB)
Supplementary file7 Video_2.2: During maximal activation of thumb extensors and abductors, only discrete tremor of the right thumb is seen. In the middle of the recording, the patient is instructed to activate his thumbs with lesser strength, resulting in the emergence of clear bilateral TT. (MP4 5014 KB)
Supplementary file8 Video_3: Action MPMC Video_3.1: Action (postural) MPMC affecting fingers bilaterally. Video_3.2: Frequent MPMC affecting left fingers upon lifting of the left hand. Video_3.3: Frequent MPMC jerks resembling piano playing movements are seen in postural condition, affecting mainly the patient’s right fingers. Video_3.4: Very fine frequent MPMC affecting mainly right fingers. (MP4 9332 KB)
Supplementary file9 Video_4: Action tremor Video_4.1: Bilateral postural hand tremor. Video_4.2: Coarse action tremor on the attempt to move very weak right hand. Video_4.3: Coarse tremor of both hands on lifting up arms. Video_4.4: In a very weak MND patient, coarse tremor of the left hand is seen during flexion and extension movements of the left wrist. Video_4.5: Fine bilateral postural tremor. Video_4.6: Fine bilateral postural tremor. Video_4.7: Asymmetric postural tremor affecting patient’s right hand. Video_4.8: Asymmetric postural tremor of grater amplitude in the weaker right hand. Video_4.9: Coarse bilateral postural tremor. Video_4.10: Bilateral postural hand tremor. (MP4 84152 KB)
Supplementary file10 Video 5: Kinetic tremor Video_5.1: Kinetic tremor of left hand seen on finger to nose test. Video_5.2: Asymmetric kinetic tremor affecting only patient’s right hand. Video_5.3: Asymmetric kinetic tremor of greater amplitude in the left hand. (MP4 60219 KB)
Supplementary file11 Video_6: Tremor of the abdominal wall is seen at the end of each expiration, due to forced activation of abdominal muscles. (MP4 2777 KB)
Supplementary file12 Video_7: Tremor upon voluntary activation of the right quadriceps muscle (MP4 6191 KB)
Supplementary file13 Video_8: Leg tremor occurring during examination of postural hand tremor Initially, there is a postural tremor of the left hand. As the patient sustains left arm posture, leg tremor (rhythmic abduction/adduction of the thighs) emerges (second half of the video). Leg tremor has similar amplitude and frequency as hand tremor. (MP4 22615 KB)
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Vogelnik, K., Koritnik, B., Leonardis, L. et al. Shaky hands are a part of motor neuron disease phenotype: clinical and electrophysiological study of 77 patients. J Neurol 269, 4498–4509 (2022). https://doi.org/10.1007/s00415-022-11096-w
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DOI: https://doi.org/10.1007/s00415-022-11096-w