Peripheral nerve hyperexcitability syndromes are a heterogenous group of disorders with involuntary, continuous muscle activity. The best characterized of them is Isaac's syndrome. Clinically this syndrome presents with undulating movements on muscle surface (commonly referred to as myokymia), pseudo‐myotonia, muscle hypertrophy, weight loss and hyperhidrosis.1 Widespread fasciculations and undulating movements are expected in a disease secondary to autoimmune, paraneoplastic or genetic etiologies (like mutations of HSPG2, HINT1, KCNA1 gene).1 We present a case of Isaac's syndrome in which symptoms and signs were limited to the left side of the body.
Case Report
A 25‐year‐old man presented with abnormal muscle twitching and stiffness over the left half of his body for the last 6 years. Initially, the twitches involved the muscles of the left calf followed by arm, thigh and trunk muscles of the left side within a span of 2 years. These twitches were painful and caused abnormal movement across the joints hampering his daily activities (Video 1). There was no history of toxin exposure. Examination revealed loss of hair on the left half of the body with focal pigmentation and skin changes akin to peau d'orange. There was no underlying mass on palpation. There were no dysmorphic features. Muscle spasms were noted over the left pectoralis major muscle, left triceps, left flexor pollicis brevis and left latissimus dorsi. The electrophysiological characteristics of F waves (Latency [Right median 26.5 ms vs. Left median 26.3 ms], Amplitude [Right median 9.1 mv vs. Left Median 1.5 mv, Right peroneal 3.1 mv vs. Left peroneal 2.3 mv] and F/M ratio [Right Median 46.1% vs. Left median 13.9%, Right peroneal 52% vs. Left peroneal 26%]) were suggestive of giant F waves with normal latencies. The H/M ratios on tibial nerve stimulation on right and left side were 0.26 and 0.20. Motor evoked potentials were not done due to technical issues. An electromyographic study showed myokymic and neuromyotonic discharges during recording of spontaneous activity in left biceps, left paraspinal muscles and left quadriceps (Fig. 1). A repetitive nerve stimulation test showed after discharges in left trapezius. Viral markers and vasculitis profile were negative. Serum creatine phospho‐kinase, calcium and thyroid stimulating hormone levels were within normal limits. Autoimmune (anti‐ NMDA, anti‐ LGI1 anti‐ CASPR2, anti‐ AMPA 1/AMPA 2, anti‐ GABA‐B) and paraneoplastic antibody profile (anti‐ Hu, anti‐ Ri, anti‐ Yo, anti‐ CV2, anti‐ PNMA‐2, anti‐ amphiphysin, anti‐ SOX1, anti‐ Tr, anti‐ GAD65, anti‐ Zic‐4) done in serum by indirect immunofluorescence assay was negative. CSF analysis could not be done as the patient did not give consent for a lumbar puncture. Awake EEG showed normal background alpha activity with no significant asymmetry. MRI brain and cervical spine was non‐contributory. Skeletal survey was normal. A PET scan of the whole body did not show any abnormal uptake. He was given 5 days of intravenous methylprednisolone at 1 gm/day followed by 5 cycles of plasmapheresis. Considering a possibility of an already described case of unilateral Satoyoshi syndrome as the cause of neuromyotonia,2 his hormonal profile (FSH, LH, testosterone, prolactin, baseline cortisol, glycosylated hemoglobin) was evaluated before methyl‐prednisolone therapy which came out normal. He did not have the other characteristic features seen in Satoyoshi syndrome like diarrhea, skeletal abnormalities and alopecia.3 He had significant improvement in symptoms after plasmapheresis and steroids. Finally considering an autoimmune etiology as the cause of neuromyotonia due to response to immunomodulation, he was discharged on azathioprine and steroids.
Video 1.
Myokymias involving left pectoralis muscle and erector spinae. Movement of left arm due to continuous muscle activity.
FIG. 1.
Left sided hemi‐body hair loss (bold arrowhead), Peau d'orange pattern of skin puckering on left trunk(arrow head), and neuromyotonia in left quadriceps.
Discussion
We had a patient with hemi‐myokymia and electrophysiological studies confirmed neuromyotonia localized to the left half of the body.
The differential diagnosis in such a case remains whether the undulating movements are due to a central disorder like Satoyoshi syndrome or peripheral nerve hyperexcitability. Hemisyndromes are generally described with central disorders likely Rasmussen encephalitis and Parry Romberg syndrome4, 5 where associated abnormalities of MRI brain are found. Our case had neither extramuscular manifestations of Satoyoshi syndrome nor abnormal MRI brain and cervical spine.
EMG studies are the gold standard for diagnosis in such cases. Spontaneous high frequency (150–250 Hz) decremental repetitive discharges of single motor unit with a MUAP morphology is the hallmark of neuromyotonia. Because of their same origin from a motor unit, fasciculations, doublets and myokymic discharges are commonly seen in cases of neuromyotonia.6 In Satoyoshi syndrome, involuntary motor unit discharges of 40–50 Hz and 4–10 mV amplitude (in the intraburst frequency of myokymia) has been described and postulated to originate from alpha motor neuron level.7 Since our patient had EMG evidence of both myokymia (intraburst frequency of 40–60 Hz) and neuromyotonia (intraburst frequency of 150–250 Hz), he may fit more into a peripheral disorder like Isaac's syndrome. In nerve conduction studies, H/M ratio of >50% on tibial nerve stimulation may also give a clue for underlying central disorder which was not in our case. On the contrary, the giant F waves in our case may suggest excitability of motor nerve and its axons due to autoimmune antibodies.8
There are several causes of neuromyotonia which include conditions causing axonal damage (local nerve irradiation), inflammatory/ inherited neuropathies, genetic mutations affecting potassium channels and auto‐antibody mediated disorders (CASPR2, LGI1, netrin 1 receptor).7, 8 Anecdotal associations of neuromyotonia with toxins like lead, silver, gold and ayurvedic drugs has also been reported.1, 9, 10 In autoimmune neuromyotonias, LGI1 and CASPR2 antibodies are identifiable in only 40% of the cases.11 Although no autoimmune markers were positive in our case, the patient responded well to steroids and plasmapheresis. This favors well for an autoimmune etiology.
To the best of our knowledge, this is the first case of hemi‐Isaac's syndrome or acquired neuromyotonia with hemi‐body phenotype.
Author Roles
(1) Research Section: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript: A. Writing of the first draft B. Review and Critique.
S.K.: 1C
P.G.: 1C
A.A.: 1C
A.D.: 1A, 1B, 1C, 3A
A.K.P.: 2A, 2B, 2C
A.K.S.: 3B
Disclosures
Ethical Compliance Statement
The authors confirm that approval of Institutional ethical committee was not required for this work. Informed consent form was taken from the patient. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.
Funding Sources and Conflicts of Interest
The authors declare that there are no funding sources or conflicts of interest relevant to this work.
Financial Disclosures for the Previous 12 Months
None to be disclosed.
Acknowledgments
The authors thank the patient for giving consent for publication of his videos and pictures for educational purpose.
Relevant disclosures and conflicts of interest are listed at the end of this article.
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