Unilateral Upper‐Limb Tremor Due to C6 Radiculopathy and Demyelinating Neuropathy

We report a patient with unilateral upper-limb tremor associated with a C5/6 radiculopathy in the setting of multifocal acquired demyelinating sensory and motor neuropathy (MADSAM)/(Lewis–Sumner syndrome). A significant pathogenic role of radiculopathy was suggested by restriction of electromyography (EMG) bursting to muscles with C6 innervation. A 49-year-old man presented with a 2-year history of left-arm tremor triggered predominantly by left-elbow flexion. He had difficulty carrying trays and was unable to pour drinks at work. He reported left-hand numbness in the lateral 3 digits. There were later mild sensory symptoms in the feet, noted only on direct questioning. There was no history of radicular pain or weakness. With the arms outstretched and prone, there were low-amplitude twitches of the left biceps, brachioradialis, and triceps. Elbow flexion with the arms in the wing-beating position, and during finger nose testing, elicited angle-dependent rhythmic contraction of the left biceps and brachioradialis muscles (Video 1). There was no rest tremor. Upper-limb power was normal with absent biceps and brachioradialis and reduced triceps jerks bilaterally. Pinprick sensation was reduced over the radial left forearm. Lower-limb power, reflexes, and sensation were normal. Magnetic resonance imaging showed severe degenerative left C5/6 foraminal stenosis (Fig. 1). Nerve conduction studies showed an upper- and lower-limb sensory neuropathy, motor conduction block of median nerve at the forearm and left tibial nerve, and prolongation of median and tibial F waves, suggestive of a multifocal demyelinating neuropathy (Table S1). Needle electromyography demonstrated chronic partial denervation in the left biceps brachii and brachioradialis muscles, consistent with a coexistent chronic C5/6 radiculopathy. Cerebrospinal fluid showed normal protein and cell count. The patient was diagnosed with MADSAM, a subtype of chronic inflammatory demyelinating polyneuropathy (CIDP), to account for his sensory symptoms. Intravenous immunoglobulin (0.4 g/kg, 1 dose given 4-weekly) improved neuropathy symptoms for 3 weeks each cycle; however, his tremor did not improve. Left C6 nerve root block was attempted but unsuccessful. Surface EMG showed rhythmic 4-Hz EMG bursts over the left biceps, with arms held in the nose-targeting position (Fig. 1). When asked to hold a pen like a cigarette, there was poorly formed intermittent synchronous EMG bursting of low amplitude in the left brachioradialis in addition to the biceps (Fig. 1). No EMG bursting was seen in muscles predominantly supplied by C5 (rhomboids) or C7 (triceps) nerve roots, either at rest or with activation. There was a reduction in the frequency and amplitude of EMG bursting with peripheral loading (Fig. 1). OnabotulinumtoxinA injections targeting the left biceps, brachialis, and brachioradialis muscles significantly improved tremor (Video 1) but were discontinued after 3 years due to excessive weakness in injected muscles, with only minor recurrence of tremor after 6 to 12 months, despite improvement in weakness. We present a patient with unilateral upper-limb tremor, with findings of elbow angle-dependent rhythmic EMG bursting isolated to C6-innervated muscles. We suggest this is consistent with a tremor of peripheral origin due to C6 nerve root pathology with coexistent MADSAM. Tremor associated with radiculopathy has only rarely been reported (Table 1).1, 2 Tremor in our patient was mediated by EMG bursting restricted to muscles with C6 innervation, as demonstrated by both surface and needle EMG. Tremor frequency reduced in response to mechanical loading, further suggesting a peripheral origin of tremor.3 It is relevant that the frequency of EMG bursting was at 4 Hz, as the resonant frequency of the elbow is 3 to 4 Hz and decreases with peripheral loading,4 sharing features seen in our patient. There was no reduction in muscle power, and tremor was present in postural conditions when muscles did not contract against resistance. This argues against a give-way phenomenon explaining this presentation. Physiological tremor has been shown to increase in amplitude with muscle shortening.5 It is possible that tonic activation of affected muscles played a role in our patient, as they will have a subset of muscle fibers firing at the resonant frequency of the body part. Upper-limb tremor is a recognized feature of demyelinating neuropathies. Neuropathic tremor is most commonly reported in inflammatory neuropathies, including CIDP.6 It is typically a postural and action tremor with a frequency gradient from distal to proximal muscles, which paradoxically does not change with peripheral loading.6, 7 These findings suggest that tremor is generated by a central processor that is influenced by abnormal peripheral nerve conduction.6, 7 It has been hypothesized that impaired sensory afferent feedback to the thalamus and subsequently the cerebellum can potentiate neuropathic tremor.8 Pseudoathetosis, but to our knowledge not tremor, has been reported in MADSAM.9 Tremor has however been reported in multifocal motor neuropathy.7, 10 In 1 series, there was no correlation between clinical neuropathy and tremor severity, and the phenotype ranged from postural, action, rest, and "jerky."7 In 1 case, tremor was more marked in clinically weaker muscles.10 We hypothesize that both cervical radiculopathy and MADSAM contributed to tremor pathogenesis in our patient due to a combination of impaired sensory feedback and neurogenic contraction of the affected muscles interacting with the resonant frequency of the elbow. (1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical analysis: A. Design, B. Execution, C. Review and critique; (3) Manuscript preparation: A. Writing of the first draft, B. Review and critique. S.A.N.: 1A, 1B, 3A, 3B N.H.: 1A, 1B, 3A, 3B M.S.: 1A, 1B, 1C, 3B V.S.C.F.: 1A, 1B, 1C, 3B Ethical Compliance Statement: This work did not require ethics committee approval. The patient provided written consent. 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: Sai A. Nagaratnam, Nimalan Harinesan, and Matthew Silsby have no additional disclosures to report. Victor S.C. Fung receives a salary from NSW Health; has received unrestricted research grants from the Michael J. Fox Foundation, AbbVie, and Merz; and receives royalties from Health Press Ltd and Taylor and Francis Group LLC. Open access publishing facilitated by The University of Sydney, as part of the Wiley - The University of Sydney agreement via the Council of Australian University Librarians. Data sharing not applicable to this article as no datasets were generated or analysed during the current study. Table S1. Nerve conduction studies performed on the left upper and lower limbs demonstrating conduction block affecting the median nerve, with reduction in sensory amplitudes. F wave latencies were prolonged for the median and tibial nerves. Needle EMG (electromyography) examined C5-T1 nerve roots, including rhomboid major (C4/5, prior to brachial plexus), showing chronic neurogenic changes affecting the C6 nerve root. Abnormal values are shown in bold font. ADM, abductor digiti minimi; Amp, amplitude; APB, abductor pollicis brevis; Dur, duration; EDB, extensor digitorum brevis; Fasc, fasciculation potentials; FDI, first dorsal interossei; FHB, flexor hallicus brevis; Fib, fibrillation potentials; L, left; Lat, latency; Max, maximum; m/s, metre/second; ms, milliseconds; Min, minimum; mV, millivolts; μV, microvolts; N, normal; NR, not recordable; PSW, positive sharp waves; Rec., recording; Stim., stimulating; Vel, velocity. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.