Myotonic dystrophy type 1 (DM1) is considered the most common type of adult-onset muscular dystrophy and is known to be related to cytosine-thymine-guanine (CTG) repeat expansion in the myotonic dystrophy protein kinase (DMPK) gene [1]. DM1 is a multisystem disease that presents with motor weakness, including the distal limb muscles and facial muscles, with manifestations including ptosis, myotonia, cataracts, dyslipidemia, and cardiac involvement [2,3].

Due to the multisystem involvement of DM1, studies have reported stroke occurrence in DM1 patients, including reports of cardioembolism [4,5] and stroke-like episodes [2]. However, the exact pathomechanism of stroke in DM1 patients has not been well established [2,5]. Additionally, antiphospholipid syndrome (APS) is a disease that can cause an embolic infarction, but there have been no reported cases of APS in DM1 patients [6]. Here, we introduce the rare case of a DM1 patient who suffered from a stroke co-occurring with APS.

A 46-year-old woman visited the emergency department due to aphasia, urinary difficulty, and gait disturbance in June 2019, which occurred on the same day. Brain magnetic resonance imaging showed multiple embolic infarctions in the bilateral posterior watershed zones (Fig. 1). The blood test results showed a fasting glucose level of 87 mg/dL, a total cholesterol level of 199 mg/dL, a low-density lipoprotein level of 89 mg/dL, and a hemoglobin A1c level of 5.4%, indicating that the patient did not have diabetes or hyperlipidemia. Furthermore, the laboratory results related to coagulation, including prothrombin time, activated partial thromboplastin time, and D-dimer level, which is known to be related to oral contraceptive medication, were normal. Electrocardiography also showed a normal sinus rhythm. She had previously taken oral contraceptives for several years after two miscarriages and menopausal transition symptoms. She was diagnosed with APS through three consecutive tests confirming antinuclear antibody, anti-β2-glycoprotein I antibody, and anticardiolipin antibody. After the diagnosis of cerebral embolic infarction, she stopped using oral contraceptives, and started warfarin to prevent recurrence.

She visited the Department of Rehabilitation Medicine for post-stroke rehabilitation. Physical examinations showed bilateral weakness of the upper and lower extremities, with generally good grades in the upper and lower extremities, except for both finger flexion, which had a fair-plus grade. According to the patient, the weakness in both hands started several decades ago, which did not match the patient's symptoms of cerebral infarction. Therefore additional history-taking and another examination were needed. Notably, in her family history, one of her five siblings (the first sister) had been diagnosed with DM1, with symptoms including difficulty walking up the stairs and weakness in both upper and lower extremities. Therefore, we recommended genetic testing and an electrodiagnostic (EDX) study her. As a result of genetic testing, our patient, as well as her first and fourth older sisters, was newly diagnosed with DM1 with the expansion of more than 150 repetitions of unstable CTG repeats in the DMPK gene.

In EDX, a nerve conduction study showed decreased amplitudes of compound muscle action potentials in the right common peroneal nerve recording at the tibialis anterior (TA) and the left common peroneal nerve recording at the extensor digitorum brevis and TA muscles (Table 1). On needle electromyography, we found abnormal spontaneous activities, including prominent myotonic discharges at rest, in the right biceps brachii, flexor carpi radialis (FCR), extensor digitorum communis (EDC), first dorsal interosseous (FDI), vastus medialis, TA, and medial head of gastrocnemius (GCM) muscles. Small, short, or polyphasic motor unit action potentials were observed in the right FCR, EDC, TA, and medial head of GCM muscles. Furthermore, the examination showed early recruitment patterns in the right biceps brachii, FCR, EDC, FDI, and the medial head of GCM muscles (Table 2). Based on the EDX, we concluded that the patient had myotonic dystrophy, mainly involving the upper and distal lower extremities (more involving the upper extremities), clinically corresponding to DM1.

Currently, the patient is receiving neurorehabilitation at our outpatient clinic for the sequelae of cerebral infarction and DM1, including gait training and occupational therapy for weakness in both hands. Comprehensive physical and occupational rehabilitation therapy has ameliorated her balance and activities of daily living, with her Berg balance score improving from 49 to 53, and her Korean version of modified Barthel index improving from 68 to 93.

To the best of our knowledge, this is the first reported case of a DM1 patient with a stroke accompanied by APS. Sugie et al. [5] stated that cardiogenic embolism is a major cause of stroke in DM1 patients and emphasized that the CTG repetition numbers were generally higher (1,000-1,500) in DM1 patients with stroke. However, our patient showed a notably different risk factor, APS, which contributed to stroke through a thrombogenic mechanism [7].

According to Tieleman et al. [6], DM2 has a stronger association with autoimmune disease than DM1. A few case reports have described stroke in DM1 patients [2,5], but no cases of APS-induced stroke have been reported to date in DM1 patients. Although there were previous reports of co-existing autoimmune diseases, these reports only involved Sjögren’s syndrome or Crohn’s disease in DM1 patients [6,8].

In a few cases of stroke occurrence in DM1, other risk factors such as dyslipidemia and arrhythmia were additionally identified [5], but it has yet to be elucidated how the DM1 disease entity affects the pathomechanism of stroke has not yet been elucidated [4,5]. Additionally, unlike DM2, it had not been confirmed whether DM1 co-existed with autoimmune diseases such as APS [6]. Finally, the rarity of this case is underscored by the fact that APS has not been reported among the causes of embolic stroke in DM1.

In addition, when the patient visited the hospital, the bilateral distal dominant weakness was not related to the actual location of the infarction. Therefore, when these symptoms are present, a further study should be conducted to rule out the possibility of other concurrent diseases. In this case, the patient was additionally diagnosed with DM1 and the etiology was identified; thus, surveillance education for possible complications and genetic counseling were possible [9].

As mentioned above, APS and DM1 are both multisystem diseases and may be accompanied by various systemic symptoms. In particular, stroke can severely deteriorate function in daily life in APS or DM1 patients. Therefore, to predict and prevent stroke in DM1 patients, it is very important to pay attention to the relationship between APS and DM1. Based on this case, we can consider the need for more early and active evaluation starting at the initial stage by considering the co-occurrence of autoimmune diseases such as APS as a risk factor for stroke in DM1 patients. Furthermore, it is necessary to consider whether autoantibody-positive findings in APS are related to the genetic abnormalities seen in DM1. This case provides new insight into the clinical mechanisms underlying the association between DM1 and APS from the standpoint of stroke occurrence.