Diagnostic Crossroads: Coexistence of Myotonic Dystrophy Type 1 and Hirayama Disease in a Case Report

Sir, Myotonic dystrophy type 1 (DM1) is the most common adult-onset muscular dystrophy.[1] It is an autosomal dominant disease caused by a CTG trinucleotide expansion in the DMPK gene’s 3′ untranslated region. Features include myotonia, progressive distal muscle weakness, and systemic symptoms like cardiac, respiratory, CNS (somnolence, apathy, fatigue), gastrointestinal, endocrine issues, and cataracts.[2] Hirayama disease (HD) causes asymmetric forearm and hand muscle weakness and atrophy, sparing the brachioradialis, primarily affects young Asian males, and is non-progressive and non-familial.[3] We present the first reported case of concurrent DM1 and HD, highlighting the clinical, neurophysiological, and genetic aspects of this diagnostic odyssey in neurology outpatient care. A 31-year-old right-handed man presented with a gradually worsening weakness in his left hand muscles over past five years. This weakness had impacted his ability to perform everyday tasks, such as buttoning his shirt, tying his shoelaces, and lifting heavy objects. Over the course of five years, he had also noticed a progressive thinning of the muscles in his left hand and forearm. He denied symptoms in the lower limbs, proximal arms, shoulder-girdle, face, neck, or bulbar muscles, as well as respiratory, cardiac, gastrointestinal, or central nervous system. Medical history excluded diabetes, trauma, febrile illness, poliomyelitis, or exposure to toxins or heavy metals. The family history did not contribute any contextual information to the clinical presentation. He wasn’t aware of neuromuscular diseases in his immediate or distant relatives. Neurological assessment revealed handgrip and percussion myotonia in the thenar and forearm muscles bilaterally, frontal balding, and bilateral wasting of the temporalis and masseter muscles [Figure 1a]. Neck flexor and extensor muscle power was graded as MRC (Medical Research Council) grade four. Asymmetrical wasting and weakness, more pronounced on the left, affected intrinsic hand muscles and forearm muscles-like pronators, wrist flexors, and extensors, with the brachioradialis muscle relatively spared [Figure 1b]. Deep tendon reflexes were normal, as were sensory tests for light touch, position, temperature, and 2-point discrimination.Figure 1: (a) Myotonic facies—Bilateral temporalis and jaw muscles atrophy with frontal balding (b) Atrophy of bilateral forearm muscles and intrinsic hand muscles, with the classical sparing of the brachioradialis, is observed, with the left limb significantly more affected than the rightLaboratory tests, including fasting blood sugar, and a 12-lead ECG were normal. The Nerve Conduction Study (NCS) revealed attenuated left ulnar compound muscle action potentials at rest, while median compound muscle action potentials were normal. Sensory nerve action potentials also showed normal findings. Electromyography (EMG) demonstrated generalized myotonia and myopathic potentials across all examined muscles, including both the first dorsal interossei, left extensor digitorum communis, left flexor carpi ulnaris, and right medial gastrocnemius, with a normal recruitment pattern. Additionally, myopathic and larger polyphasic potentials were observed in the left extensor digitorum communis, flexor carpi ulnaris, and bilateral first dorsal interossei muscles, indicating a myopathic process with chronic denervation, predominantly affecting C8 and T1. Initially, we suspected cervical myelopathy akin to Hirayama disease due to asymmetric distal muscle involvement and distinctive “oblique” forearm muscle atrophy. However, features like hatchet facies, frontal balding, and myotonia prompted consideration of DM1, supported by electrophysiological findings. Consequently, we conducted cervical spine MRI and DM1 genetic testing. The MRI images in neutral non-flexed position showed lower cervical cord atrophy with segmental intramedullary hyperintense signal at C5-C6 levels [Figure 2]. Flexion cervical spinal MRI images showed forward displacement of the posterior dural wall and widening of the lamino-dural space, extending from C3 level distally in cervical spine and proximal dorsal spine with multiple flow voids, resulting in near-complete obliteration of the subarachnoid space and compression of the cervical cord at C5 and C6 levels. Post-gadolinium T1-weighted images displayed homogeneous enhancement in the expanded posterior epidural space with flow voids, along with an asymmetrically flattened atrophic cord at the aforementioned levels. These imaging findings have been described in the literature to be characteristic of HD.[4]Figure 2: MRI images: (a, b) Neutral T2W sagittal and axial images show asymmetric flattening and atrophy of the lower cervical cord with segmental intramedullary hyperintensities at C5-C6 levels. (c, d) Flexion T2W sagittal and axial images show hyperintense cord signal (white arrow), forward displacement of the posterior dural wall, widened lamino-dural space (yellow arrowhead), and multiple flow voids, leading to near-complete subarachnoid space obliteration and cord compression at C5 and C6. (e, f) Post-gadolinium fat-suppressed T1W flexion MR images show homogeneous enhancement in the expanded posterior epidural space (yellow arrowhead) and asymmetrically flattened atrophic cord (white arrow) at C5The analysis of the CTG repeats, using triplet repeat primed PCR (TP-PCR), in the 3’ UTR region of the DMPK gene revealed an unstable expansion of over 50 CTG repeats on one allele and approximately 11 CTG repeats in the other allele, thus confirming the genetic diagnosis of DM1.[2] However, the assay’s limitations prevented precise quantification of the exact number of repeats. A cervical collar and physiotherapy were initiated, but no treatment for myotonia was started as it did not affect the activities of daily living. HD involves a loss of dural canal slack during extension, resulting in a tight canal that can’t accommodate the posterior wall length during flexion, leading to anterior shifting, cord compression, microcirculatory disturbances, and potential anterior horn cell necrosis from chronic circulatory disturbance during neck flexion.[3] Considering this, repeated microinjuries from neck flexion may have been exacerbated by weakened neck muscles in our patient. Asymmetric distal involvement, mainly in C8 and T1 myotomes with “oblique” forearm muscle atrophy, neurogenic potentials in C8-T1 on EMG, upper limb restriction over 5 years, and typical MRI findings, led to HD diagnosis. Concurrent DM1 was considered due to typical facies, myotonia, weakness in neck muscles, and genetic testing confirmation. We could not examine his family members as it was not feasible in our case. One potential explanation for the absence of DM1 in the family could be the presence of subtle or subclinical disease with fewer repeat expansions. Management for HD may involve a cervical collar or surgery,[3] while DM1 requires antimyotonia medications, regular evaluation for complications, adherence to anesthesia guidelines, and monitoring of pulmonary, cardiac, and other symptoms.[5] Diagnosing DM1 facilitates genetic risk assessments, counseling, and comprehensive management. An inverse correlation exists between the age at onset and the number of repeats, with disease severity also correlating with repeat size. Typically, mildly affected patients harbor 50 to 150 repeats, classic DM1 patients have 100 to 1000 repeats, and congenital cases may exhibit more than 2000 repeats.[2] However, due to assay limitations, we couldn’t precisely quantify the repeats in our patient. This case illustrates Hickam’s dictum, as it showcases the coexistence of HD and DM1, both of which can cause distal muscle weakness and wasting, and highlights the importance of considering multiple diagnoses, especially since HD can be arrested with appropriate intervention. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.