Differential Diagnostic Decision-Making Scheme for Limb Weakness and Bilateral Temporal Pole Abnormal Signals

Differential Diagnostic Decision-Making Scheme for Limb Weakness and Bilateral Temporal Pole Abnormal Signals | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Differential Diagnostic Decision-Making Scheme for Limb Weakness and Bilateral Temporal Pole Abnormal Signals Hengye Zhao, Qian Liang, Yibin Hu, He Li, Wei Tang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8370605/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Background : Myotonic dystrophy type 1 (DM1) is an autosomal dominant disorder caused by an abnormal expansion of the CTG trinucleotide repeat in the 3′UTR region of the DMPK gene on chromosome 19q13.3. There is currently no cure for DM1, and early diagnosis along with multidisciplinary evaluation and intervention may be important in delaying its progression. However, its clinical manifestations are diverse, making diagnosis quite challenging. Case Report : A 29-year-old female patient with a 6-year history of progressive limb weakness accompanied by muscle twitching. The patient also exhibited clinical myotonia and abnormal findings in both temporal lobes on cranial MRI. She was finally diagnosed with DM1 through electromyography and genetic testing. Myotonic Dystrophy Type 1 Limb Weakness Bilateral Temporal Pole Abnormal Signals Figures Figure 1 Figure 2 Figure 3 Introduction A 29-year-old woman presented with a 6-year history of progressive limb weakness accompanied by muscle fasciculations. Initially, she experienced clumsiness in daily activities, exertional fatigue, and inability to walk for prolonged periods. Over the past three years, she developed increasing difficulty ascending and descending stairs, and currently requires assistance. She had marked difficulty rising from a squatting position, was unable to carry heavy objects with her upper limbs, and exhibited mildly slurred speech. Occasionally, she experienced difficulty releasing her grip after forceful hand closure. These symptoms gradually worsened over time, without associated muscle pain. Her past medical history was unremarkable, and her immediate family members were healthy. Neurological examination revealed that she was alert and cognitively intact. Dysarthria was present, with mild left eyelid ptosis and a positive eyelash sign. The gag reflex was preserved. Muscle strength was grade 4 in the neck flexors as well as proximally and distally in both the upper and lower limbs. Atrophy was observed in the bilateral thenar and hypothenar muscles, sternocleidomastoid, trapezius, latissimus dorsi, and rhomboid muscles. Percussion of the thenar, hypothenar, and tongue muscles elicited sustained stiffness (percussion myotonia). Muscle tone was moderately increased (++). Deep tendon reflexes were symmetrically absent in all extremities, plantar responses were negative, and sensory examination was normal. Cranial Magnetic Resonance Imaging (MRI) revealed abnormal signal lesions in the bilateral temporal pole white matter (Figure 1). Electrocardiogram (ECG) and echocardiography were unremarkable. Pulmonary function testing demonstrated a moderate restrictive ventilatory defect with mildly reduced diffusion capacity. Ophthalmological examination showed bilateral optic nerve atrophy. Laboratory studies, including serum biochemistry, autoimmune antibody panel, thyroid function tests, antiphospholipid antibody panel, vitamin B12, blood lactate, creatine kinase (CK), creatine kinase-MB (CK-MB), and cardiac troponin, were all within normal limits. Diagnostic Considerations: Two key diagnostic clues in this patient were identified: myotonia and bilateral temporal pole lesions. Narrowing the diagnostic spectrum by selecting disorders that feature both findings was crucial for differential diagnosis. Bilateral temporal pole lesions can be observed in infectious diseases (e.g., herpes simplex virus encephalitis, congenital cytomegalovirus infection), muscular disorders (e.g., myotonic dystrophy type 1 [DM1]), metabolic diseases (e.g., mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes [MELAS], hyperammonemia), vascular diseases (e.g., cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy [CADASIL]), as well as neoplastic and paraneoplastic conditions [1] . Myotonia, defined as delayed relaxation of muscle after voluntary contraction or percussion, requires differentiation from congenital myotonia, paramyotonia congenita, myotonic dystrophy, and drug-induced myotonia (following exposure to agents such as antimalarials, chloroquine, statins, colchicine, or immune checkpoint inhibitors). By intersecting the disease spectra associated with “myotonia” and “bilateral temporal pole lesions,” DM1 emerges as the primary diagnostic consideration (Figure 2). Supportive diagnostic modalities include electromyography (EMG) and genetic testing. In addition, progressive limb weakness with fasciculations necessitates differentiation from amyotrophic lateral sclerosis (ALS). However, the absence of pathological reflexes and the presence of percussion myotonia argue against ALS, and EMG serves as a critical tool for exclusion. The chronic disease course, absence of fever or myalgia, and lack of inflammatory features did not support intracranial infection or inflammatory conditions, making cerebrospinal fluid (CSF) testing unnecessary. Muscle biopsy in DM typically shows non-specific myogenic changes without distinctive features compared to other myopathies [2] . Given that EMG and genetic testing are generally sufficient for establishing a diagnosis, muscle biopsy was not considered essential in this case. EMG demonstrated chronic myogenic changes in multiple limbs, with widespread myotonic discharges resembling a “dive-bomber sound,” most prominently in distal muscles (Video S2). Genetic Testing: Genetic analysis revealed an abnormal expansion of CTG repeats (>50 copies) in the 3’ untranslated region (3’UTR) of the dystrophia myotonica protein kinase (DMPK) gene in the patient. The patient’s elder sister also carried an abnormal CTG repeat expansion (>50 copies) in the DMPK gene 3’UTR, but remained asymptomatic, exhibiting only percussion myotonia of the thenar muscle upon clinical examination. Diagnosis: Electromyography (EMG) revealed myogenic changes accompanied by myotonic discharges with the characteristic “dive-bomber sound” pattern. Genetic testing demonstrated an abnormal expansion of CTG repeats (>50 copies) in the 3′UTR of the DMPK gene. Taken together with the patient’s clinical manifestations, these findings fulfilled the clinical diagnostic criteria for adult-onset DM1 as proposed by Nguyen and Campbell [2] . Treatment: The patient received neurotrophic therapy with vitamin B1 and mecobalamin, along with guidance for limb functional rehabilitation exercises. Discussion Myotonic dystrophy(DM) is an autosomal dominant disorder caused by abnormal expansion of CTG trinucleotide repeats in the 3′UTR of the DMPK gene located on chromosome 19q13.3 DM1 can be classified into congenital, childhood-onset, adult-onset, and late-onset forms. The present patient belongs to the adult-onset subtype. Adult-onset DM1 typically manifests after the age of 10 years and is characterized by muscle weakness, myotonia, muscle atrophy, and early-onset cataracts. The most common initial symptom is grip myotonia. However, patients may also develop facial and extraocular muscle atrophy, respiratory muscle weakness, and mild-to-moderate cognitive impairment. Cardiac conduction defects, thyroid dysfunction, and diabetes mellitus are also frequently observed, reflecting the multisystemic involvement of DM1 [3] . Given its heterogeneous presentation, diagnosis can be challenging. Distinctive features such as a “hatchet face,” myotonia, percussion myotonia, and EMG findings of myotonic discharges with a characteristic “dive-bomber sound” are important diagnostic clues, while genetic testing provides definitive confirmation.（The diagnostic thinking diagram for myotonia：Figure 3） White matter abnormalities represent a frequent neurological manifestation of DM1, most commonly affecting the periventricular regions, frontal lobes, and temporal lobes, whereas the thalamus and basal ganglia are usually spared. Approximately one-third of DM1 patients exhibit bilateral temporal pole lesions. Such white matter changes may be associated with fatigue, excessive daytime sleepiness, depression, seizures, and cognitive decline. In this case, neuroimaging already demonstrated bilateral temporal lobe abnormalities, though the patient did not yet show marked cognitive impairment. This suggests that central nervous system involvement in DM1 may precede overt clinical manifestations. Of note, the patient’s niece presented with intellectual disability, which has been more frequently associated with childhood-onset DM1, underscoring the importance of genetic testing and close monitoring in affected families. The differential diagnosis of bilateral temporal pole abnormalities includes CADASIL, radiation-induced encephalopathy, and metabolic disorders such as MELAS. CADASIL is supported by additional findings such as microbleeds, cerebral atrophy, enlarged perivascular spaces, and lacunar infarcts, whereas MELAS is characterized by exercise intolerance and post-exertional lactic acidosis. In patients with myotonia, other differential considerations include congenital myotonia, paramyotonia congenita, and drug-induced myotonia. The former two typically present in infancy or early childhood and require genetic confirmation, while drug-induced myotonia can result from agents such as statins or colchicine and may resolve after drug discontinuation. Currently, no curative treatment exists for DM1. Management is primarily symptomatic. Mexiletine has been shown to improve grip strength in DM1 patients, while moderate-intensity aerobic exercise may provide benefit in terms of muscle weakness and cardiopulmonary function [4] . In one study, metformin therapy improved six-minute walk distance by approximately 30 meters compared with placebo (23 participants, 57.5%) [5] . Gene-targeted therapies are under investigation, but most remain in preclinical stages without robust evidence from clinical trials. Overall, adult-onset DM1 typically follows a slow course and does not significantly shorten life expectancy. However, in patients with multisystem involvement, morbidity and mortality may result from cardiac complications, secondary pulmonary infections, or nutritional deficiencies. Therefore, genetic counseling for all first-degree relatives is essential, and multidisciplinary evaluation and early intervention should be considered when systemic involvement is identified. Patient Outcome: At one-year follow-up, the patient showed modest improvement in muscle weakness but developed mild memory impairment, likely attributable to bilateral temporal lobe involvement. Declarations Ethics Approval and Consent to Participate All procedures were performed according to the Declaration of Helsinki and ethical approval was obtained from the Ethics Committee from Affiliated Hospital of Shandong University of Traditional Chinese Medicine. All participants gave written informed consent. All participants have given informed consent to the release of personal or clinical details. Conflict of Interest Disclosures The authors declare no competing interests. Consent for publication All participants have given informed consent to the release of personal or clinical details and any images in this study. Written informed consents were obtained from all participants and a copy of the consent forms is available for the Editor to review upon request. Availability of Data and Materials This study is a case series and does not include datasets. Additional clinical information related to the cases presented is available from the corresponding author upon reasonable request and subject to appropriate ethical considerations. Author Contributions Drs Li and Tang contributed the conception; Drs Li and Zhao contributed to drafting the text and preparing the figures. Drs Liang and Hu contributed to proofreading the text. All authors have reviewed the manuscript and agreed to its publication. Additional Contributions We thank the patient for granting permission to publish this information. Study Funding This work was partially supported by the Taishan Scholars Youth Expert Program of Shandong Province(tsqn202507380). References Sureka J, Jakkani RK. Clinico-radiological spectrum of bilateral temporal lobe hyperintensity: a retrospective review. Br J Radiol. 2012;85(1017):e782–92. Nguyen CE, Campbell C. Myotonic dystrophy type 1. CMAJ. 2016;188(14):1033. Hartman J, Patki T, Johnson NE. Diagnosis and Management of Myotonic Dystrophy Type 1. JAMA. 2024;331(14):1227–8. Voet NB, van der Kooi EL, van Engelen BG, et al. Strength training and aerobic exercise training for muscle disease. Cochrane Database Syst Rev. 2019;12(12):CD003907. Bassez G, Audureau E, Hogrel JY, et al. Improved mobility with metformin in patients with myotonic dystrophy type 1: a randomized controlled trial. Brain. 2018;141(10):2855–65. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 23 Feb, 2026 Reviewers agreed at journal 15 Feb, 2026 Reviewers agreed at journal 05 Feb, 2026 Reviewers invited by journal 30 Jan, 2026 Editor assigned by journal 27 Jan, 2026 Editor invited by journal 07 Jan, 2026 Submission checks completed at journal 03 Jan, 2026 First submitted to journal 03 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8370605","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":583881428,"identity":"705ca7f0-f1a7-46a1-8e2e-400d2b2537f9","order_by":0,"name":"Hengye Zhao","email":"","orcid":"","institution":"Neurology Department of The First Clinical Medical College, Shandong University of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Hengye","middleName":"","lastName":"Zhao","suffix":""},{"id":583881444,"identity":"46afbfc3-623b-42ce-bffe-b934968457ad","order_by":1,"name":"Qian 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Hospital","correspondingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"Tang","suffix":""}],"badges":[],"createdAt":"2025-12-16 01:08:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8370605/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8370605/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":101790491,"identity":"653faa4e-8cdc-467f-9682-8167baf5bce7","added_by":"auto","created_at":"2026-02-03 16:05:39","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":125654,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCranial Magnetic Resonance Imaging (MRI) revealed abnormal signal lesions in the bilateral temporal pole white matter\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8370605/v1/3146192aac05199a3e15964a.jpeg"},{"id":101790490,"identity":"c0538006-0e1f-4ff0-9c2b-91ce19f1212a","added_by":"auto","created_at":"2026-02-03 16:05:39","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":78518,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ethe disease spectra associated with “myotonia” and “bilateral temporal pole lesions”\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8370605/v1/2f4455e7fa42590ffa583fff.jpeg"},{"id":101790492,"identity":"71d1fb9a-8478-4ed0-89ee-22aebdc412a6","added_by":"auto","created_at":"2026-02-03 16:05:39","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":73642,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe diagnostic thinking diagram for myotonia\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8370605/v1/866d051e3398773549f27e81.jpeg"},{"id":101790504,"identity":"c50a41f1-c750-45e4-b39e-ee520b91c158","added_by":"auto","created_at":"2026-02-03 16:05:44","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":746199,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8370605/v1/d0c253e5-1785-454f-8bb7-f102d3c807e8.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Differential Diagnostic Decision-Making Scheme for Limb Weakness and Bilateral Temporal Pole Abnormal Signals","fulltext":[{"header":"Introduction","content":"\u003cp\u003eA 29-year-old woman presented with a 6-year history of progressive limb weakness accompanied by muscle fasciculations. Initially, she experienced clumsiness in daily activities, exertional fatigue, and inability to walk for prolonged periods. Over the past three years, she developed increasing difficulty ascending and descending stairs, and currently requires assistance. She had marked difficulty rising from a squatting position, was unable to carry heavy objects with her upper limbs, and exhibited mildly slurred speech. Occasionally, she experienced difficulty releasing her grip after forceful hand closure. These symptoms gradually worsened over time, without associated muscle pain. Her past medical history was unremarkable, and her immediate family members were healthy.\u003c/p\u003e\n\u003cp\u003eNeurological examination revealed that she was alert and cognitively intact. Dysarthria was present, with mild left eyelid ptosis and a positive eyelash sign. The gag reflex was preserved. Muscle strength was grade 4 in the neck flexors as well as proximally and distally in both the upper and lower limbs. Atrophy was observed in the bilateral thenar and hypothenar muscles, sternocleidomastoid, trapezius, latissimus dorsi, and rhomboid muscles. Percussion of the thenar, hypothenar, and tongue muscles elicited sustained stiffness (percussion myotonia). Muscle tone was moderately increased (++). Deep tendon reflexes were symmetrically absent in all extremities, plantar responses were negative, and sensory examination was normal.\u003c/p\u003e\n\u003cp\u003eCranial Magnetic Resonance Imaging (MRI) revealed abnormal signal lesions in the bilateral temporal pole white matter\u0026nbsp;(Figure 1). Electrocardiogram (ECG) and echocardiography were unremarkable. Pulmonary function testing demonstrated a moderate restrictive ventilatory defect with mildly reduced diffusion capacity. Ophthalmological examination showed bilateral optic nerve atrophy. Laboratory studies, including serum biochemistry, autoimmune antibody panel, thyroid function tests, antiphospholipid antibody panel, vitamin B12, blood lactate, creatine kinase (CK), creatine kinase-MB (CK-MB), and cardiac troponin, were all within normal limits.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiagnostic Considerations:\u0026nbsp;\u003c/strong\u003eTwo key diagnostic clues in this patient were identified: myotonia and bilateral temporal pole lesions. Narrowing the diagnostic spectrum by selecting disorders that feature both findings was crucial for differential diagnosis. Bilateral temporal pole lesions can be observed in infectious diseases (e.g., herpes simplex virus encephalitis, congenital cytomegalovirus infection), muscular disorders (e.g., myotonic dystrophy type 1 [DM1]), metabolic diseases (e.g., mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes [MELAS], hyperammonemia), vascular diseases (e.g., cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy [CADASIL]), as well as neoplastic and paraneoplastic conditions \u003csup\u003e[1]\u003c/sup\u003e. Myotonia, defined as delayed relaxation of muscle after voluntary contraction or percussion, requires differentiation from congenital myotonia, paramyotonia congenita, myotonic dystrophy, and drug-induced myotonia (following exposure to agents such as antimalarials, chloroquine, statins, colchicine, or immune checkpoint inhibitors). By intersecting the disease spectra associated with \u0026ldquo;myotonia\u0026rdquo; and \u0026ldquo;bilateral temporal pole lesions,\u0026rdquo; DM1 emerges as the primary diagnostic consideration (Figure 2). Supportive diagnostic modalities include electromyography (EMG) and genetic testing. In addition, progressive limb weakness with fasciculations necessitates differentiation from amyotrophic lateral sclerosis (ALS). However, the absence of pathological reflexes and the presence of percussion myotonia argue against ALS, and EMG serves as a critical tool for exclusion. The chronic disease course, absence of fever or myalgia, and lack of inflammatory features did not support intracranial infection or inflammatory conditions, making cerebrospinal fluid (CSF) testing unnecessary. Muscle biopsy in DM typically shows non-specific myogenic changes without distinctive features compared to other myopathies \u003csup\u003e[2]\u003c/sup\u003e. Given that EMG and genetic testing are generally sufficient for establishing a diagnosis, muscle biopsy was not considered essential in this case.\u003c/p\u003e\n\u003cp\u003eEMG demonstrated chronic myogenic changes in multiple limbs, with widespread myotonic discharges resembling a \u0026ldquo;dive-bomber sound,\u0026rdquo; most prominently in distal muscles (Video S2).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGenetic Testing:\u0026nbsp;\u003c/strong\u003eGenetic analysis revealed an abnormal expansion of CTG repeats (\u0026gt;50 copies) in the 3\u0026rsquo; untranslated region (3\u0026rsquo;UTR) of the dystrophia myotonica protein kinase (DMPK) gene in the patient. The patient\u0026rsquo;s elder sister also carried an abnormal CTG repeat expansion (\u0026gt;50 copies) in the DMPK gene 3\u0026rsquo;UTR, but remained asymptomatic, exhibiting only percussion myotonia of the thenar muscle upon clinical examination.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiagnosis:\u003c/strong\u003e Electromyography (EMG) revealed myogenic changes accompanied by myotonic discharges with the characteristic\u0026nbsp;\u0026ldquo;dive-bomber sound\u0026rdquo;\u0026nbsp;pattern. Genetic testing demonstrated an abnormal expansion of CTG repeats (\u0026gt;50 copies) in the 3\u0026prime;UTR of the DMPK gene. Taken together with the patient\u0026rsquo;s clinical manifestations, these findings fulfilled the clinical diagnostic criteria for adult-onset DM1 as proposed by Nguyen and Campbell \u003csup\u003e[2]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTreatment:\u003c/strong\u003e The patient received neurotrophic therapy with vitamin B1 and mecobalamin, along with guidance for limb functional rehabilitation exercises.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eMyotonic dystrophy(DM) is an autosomal dominant disorder caused by abnormal expansion of CTG trinucleotide repeats in the 3\u0026prime;UTR of the DMPK gene located on chromosome 19q13.3 DM1 can be classified into congenital, childhood-onset, adult-onset, and late-onset forms. The present patient belongs to the adult-onset subtype. Adult-onset DM1 typically manifests after the age of 10 years and is characterized by muscle weakness, myotonia, muscle atrophy, and early-onset cataracts. The most common initial symptom is grip myotonia. However, patients may also develop facial and extraocular muscle atrophy, respiratory muscle weakness, and mild-to-moderate cognitive impairment. Cardiac conduction defects, thyroid dysfunction, and diabetes mellitus are also frequently observed, reflecting the multisystemic involvement of DM1 \u003csup\u003e[3]\u003c/sup\u003e. Given its heterogeneous presentation, diagnosis can be challenging. Distinctive features such as a \u0026ldquo;hatchet face,\u0026rdquo; myotonia, percussion myotonia, and EMG findings of myotonic discharges with a characteristic \u0026ldquo;dive-bomber sound\u0026rdquo; are important diagnostic clues, while genetic testing provides definitive confirmation.（The diagnostic thinking diagram for myotonia：Figure 3）\u003c/p\u003e\n\u003cp\u003eWhite matter abnormalities represent a frequent neurological manifestation of DM1, most commonly affecting the periventricular regions, frontal lobes, and temporal lobes, whereas the thalamus and basal ganglia are usually spared. Approximately one-third of DM1 patients exhibit bilateral temporal pole lesions. Such white matter changes may be associated with fatigue, excessive daytime sleepiness, depression, seizures, and cognitive decline. In this case, neuroimaging already demonstrated bilateral temporal lobe abnormalities, though the patient did not yet show marked cognitive impairment. This suggests that central nervous system involvement in DM1 may precede overt clinical manifestations. Of note, the patient\u0026rsquo;s niece presented with intellectual disability, which has been more frequently associated with childhood-onset DM1, underscoring the importance of genetic testing and close monitoring in affected families. The differential diagnosis of bilateral temporal pole abnormalities includes CADASIL, radiation-induced encephalopathy, and metabolic disorders such as MELAS. CADASIL is supported by additional findings such as microbleeds, cerebral atrophy, enlarged perivascular spaces, and lacunar infarcts, whereas MELAS is characterized by exercise intolerance and post-exertional lactic acidosis. In patients with myotonia, other differential considerations include congenital myotonia, paramyotonia congenita, and drug-induced myotonia. The former two typically present in infancy or early childhood and require genetic confirmation, while drug-induced myotonia can result from agents such as statins or colchicine and may resolve after drug discontinuation.\u003c/p\u003e\n\u003cp\u003eCurrently, no curative treatment exists for DM1. Management is primarily symptomatic. Mexiletine has been shown to improve grip strength in DM1 patients, while moderate-intensity aerobic exercise may provide benefit in terms of muscle weakness and cardiopulmonary function \u003csup\u003e[4]\u003c/sup\u003e. In one study, metformin therapy improved six-minute walk distance by approximately 30 meters compared with placebo (23 participants, 57.5%) \u003csup\u003e[5]\u003c/sup\u003e. Gene-targeted therapies are under investigation, but most remain in preclinical stages without robust evidence from clinical trials. Overall, adult-onset DM1 typically follows a slow course and does not significantly shorten life expectancy. However, in patients with multisystem involvement, morbidity and mortality may result from cardiac complications, secondary pulmonary infections, or nutritional deficiencies. Therefore, genetic counseling for all first-degree relatives is essential, and multidisciplinary evaluation and early intervention should be considered when systemic involvement is identified.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient Outcome:\u003c/strong\u003e At one-year follow-up, the patient showed modest improvement in muscle weakness but developed mild memory impairment, likely attributable to bilateral temporal lobe involvement.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics Approval and Consent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures were performed according to the Declaration of Helsinki and ethical approval was obtained from the Ethics Committee from Affiliated Hospital of Shandong University of Traditional Chinese Medicine. All participants gave written informed consent. All participants have given informed consent to the release of personal or clinical details.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest Disclosures\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll participants have given informed consent to the release of personal or clinical details and any images in this study. Written informed consents were obtained from all participants and a copy of the consent forms is available for the Editor to review upon request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of Data and Materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study is a case series and does not include datasets. Additional clinical information related to the cases presented is available from the corresponding author upon reasonable request and subject to appropriate ethical considerations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDrs Li and Tang contributed the conception; Drs Li and Zhao contributed to drafting the text and preparing the figures. Drs Liang and Hu contributed to proofreading the text. All authors have reviewed the manuscript and agreed to its publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdditional Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank the patient for granting permission to publish this information.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Funding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was partially supported by the Taishan Scholars Youth Expert Program of Shandong Province(tsqn202507380).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSureka J, Jakkani RK. Clinico-radiological spectrum of bilateral temporal lobe hyperintensity: a retrospective review. Br J Radiol. 2012;85(1017):e782\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNguyen CE, Campbell C. Myotonic dystrophy type 1. CMAJ. 2016;188(14):1033.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHartman J, Patki T, Johnson NE. Diagnosis and Management of Myotonic Dystrophy Type 1. JAMA. 2024;331(14):1227\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVoet NB, van der Kooi EL, van Engelen BG, et al. Strength training and aerobic exercise training for muscle disease. Cochrane Database Syst Rev. 2019;12(12):CD003907.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBassez G, Audureau E, Hogrel JY, et al. Improved mobility with metformin in patients with myotonic dystrophy type 1: a randomized controlled trial. Brain. 2018;141(10):2855\u0026ndash;65.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Myotonic Dystrophy Type 1, Limb Weakness, Bilateral Temporal Pole Abnormal Signals","lastPublishedDoi":"10.21203/rs.3.rs-8370605/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8370605/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Myotonic dystrophy type 1 (DM1) is an autosomal dominant disorder caused by an abnormal expansion of the CTG trinucleotide repeat in the 3′UTR region of the DMPK gene on chromosome 19q13.3. There is currently no cure for DM1, and early diagnosis along with multidisciplinary evaluation and intervention may be important in delaying its progression. However, its clinical manifestations are diverse, making diagnosis quite challenging.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase Report\u003c/strong\u003e: A 29-year-old female patient with a 6-year history of progressive limb weakness accompanied by muscle twitching. The patient also exhibited clinical myotonia and abnormal findings in both temporal lobes on cranial MRI. She was finally diagnosed with DM1 through electromyography and genetic testing.\u003c/p\u003e","manuscriptTitle":"Differential Diagnostic Decision-Making Scheme for Limb Weakness and Bilateral Temporal Pole Abnormal Signals","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-03 16:05:31","doi":"10.21203/rs.3.rs-8370605/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-02-23T12:01:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"35010284277027330031504215060779541607","date":"2026-02-15T21:46:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"160936952039452157866256053735089749933","date":"2026-02-05T06:42:59+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-30T19:54:54+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-27T09:01:10+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-07T09:14:19+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-03T14:00:23+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Neurology","date":"2026-01-03T13:54:54+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f651a606-94ed-4531-b62e-4dbae3b5e8c6","owner":[],"postedDate":"February 3rd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-02-03T16:05:32+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-03 16:05:31","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8370605","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8370605","identity":"rs-8370605","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}