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Background Although functional impairment in patients with myotonic dystrophy is an important determinant of the quality of life (QoL), patients’ subjective evaluation of their symptoms may also affect their QoL. The aim of this study was to investigate the association between subjective symptom impact and the QoL of patients with myotonic dystrophy, after controlling for functional impairment. Methods Eligible patients with myotonic dystrophy type 1 (DM1) were recruited from four hospitals in Japan. The subjective symptom impact of four symptoms (muscle weakness, fatigue, pain, and myotonia) and overall QoL were evaluated using the Individualized Neuromuscular Quality of Life (INQoL) questionnaire. Functional impairment was assessed using the modified Rankin Scale. Results Seventy-seven patients with DM1 were included in this study. Overall QoL was significantly associated with subjective symptom impact of muscular weakness, fatigue, pain, myotonia, swallowing difficulty, and droopy eyelids. In the regression models, disease duration (beta = 0.11) and moderate to severe functional impairment (beta = 0.33) explained a significant part of the overall QoL. Furthermore, muscular weakness, fatigue, and myotonia significantly explained additional variance of the overall QoL (beta = 0.17–0.43). Conclusions Subjective symptom impact and functional impairment are independent features influencing the QoL of Japanese patients with DM1.

We conducted a comprehensive anonymous questionnaire survey on medical care and treatment for patients with myotonic dystrophy, who registered in the Japanese national registry (Remudy) or were undergoing care in seven hospitals specializing neuromuscular diseases. The questionnaire consisted of 49 questions were distributed to 813 patients, and 342 valid responses were collected. Most prevalent symptoms or complaints were dysfunction of fingers and fatigue. One-third of the adult patients left the job, half of which was due to the disease. Twelve percent of the patients did not visit the specialist regularly, the main reason being distance. The most common reason that the patients did not follow the advice of using a ventilator by medical professionals was lack of feeling the need. One-fourth of the adult female patients had infertility treatment, 80% of which was before a diagnosis of this disorder. This first-time nationwide survey revealed the actual condition of Japanese patients with myotonic dystrophy and raised various care-related issues.

Introduction The Myotonic Dystrophy Health Index (MDHI) is a disease-specific, patient-reported outcome measure. The objective of this study was to translate, evaluate, and validate a Japanese version of the MDHI (MDHI-J). Methods We utilized forward and backward translations and qualitative interviews with 11 myotonic dystrophy type 1 (DM1) participants. We subsequently tested the internal consistency, test-retest reliability, concurrent validity against muscle strength, and 3 quality-of-life measures, and the known-groups validity of the MDHI-J with 60 adult patients. Results The MDHI-J was found to be culturally appropriate, comprehensive, and clinically relevant. The MDHI-J and its subscales had high internal consistency (mean Cronbach's α = 0.91), test-retest reliability (intraclass coefficient 0.678-0.915), and concurrent validity (Spearman's ρ - 0.869 to 0.904). MDHI-J scores were strongly associated with employment, duration of symptoms, and modified Rankin Scale. Discussion The MDHI-J is suitable and valid to measure patient-reported disease burden in adult Japanese patients with DM1. Muscle Nerve 59:577-577, 2019.

To clarify the influence of coronavirus disease-19 (COVID-19) on the care of muscular dystrophy patients, we performed a questionnaire survey that was posted on the internet on May 11, 2020. By the end of July 2020, 542 responses had been collected. Approximately 30% of patients postponed regular consultations, and one-quarter of patients who received consultation more than once a month used telephone consultations. Two of 84 patients with Duchenne muscular dystrophy had reduced their steroid doses. A shortage of ventilator accessories and infection protection equipment occurred following the onset of COVID-19, and this shortage had a serious impact on medical care and infection prevention measures. Reductions in rehabilitation and other services, and avoidance of outings, led to a decrease in exercise and an increase in caregiver burden. Inpatients were restricted from going out and visiting family members. More than 20% of patients reported physical or mental complaints; however, few required treatment. COVID-19 has seriously affected the activities and quality of life of patients with muscular dystrophy. We will continue this survey and analyze the longitudinal changes.

Myotonic dystrophies (DM) are inherited autosomal dominant disorders affecting multiple organs. Currently available therapeutics for DM are limited; therefore, a patient registry is essential for therapeutic development and success of clinical trials targeting the diseases. We have developed a nationwide DM registry in Japan under the Registry of Muscular Dystrophy (Remudy). The registration process was patient-initiated; however, physicians certified the clinical information. The dataset includes all Naarden and TREAT-NMD core datasets and additional items covering major DM clinical features. As of March 2020, we enrolled 976 patients with genetically confirmed DM. The majority (99.9%) of these patients had DM1, with 11.4% having the congenital form. However, 1 patient had DM2. Upon classifying 969 symptomatic DM1 patients based on their age at onset, an earlier onset was associated with a longer CTG repeat length. Myotonia was the most frequent symptom, followed by hand disability, fatigue, and daytime sleepiness. The frequency of hand disabilities, constipation, and visual disturbances was higher for patients with congenital DM. According to a multiple regression analysis of objective clinical measurements related to prognosis and activities of daily living, CTG repeat length strongly influenced the grip strength, forced vital capacity, and QRS time in an electrocardiogram. However, the grip strength was only modestly related to disease duration. This report will shed light on the Japanese national DM registry, which has recruited a significant number of patients. The registry will provide invaluable data for planning clinical trials and improving the standard of care for patients.

Background Cerebral ventriculomegaly is an abnormal feature characteristic of myotonic dystrophy type 1 (DM1). This retrospective study investigated the morphologic changes accompanied by ventriculomegaly in DM1 on brain MRI. Methods One hundred and twelve adult patients with DM1 and 50 sex- and age-matched controls were assessed. The imaging characteristics for evaluations included the z-Evans Index (ventriculomegaly), callosal angle (CA), enlarged perivascular spaces in the centrum semiovale (CS-EPVS), temporo-polar white matter lesion (WML) on 3D fluid-attenuated inversion recovery (FLAIR), disproportionately enlarged subarachnoid-space hydrocephalus (DESH), and pathological brain atrophy. The “z-Evans Index” was defined as the maximum z-axial length of the frontal horns to the maximum cranial z-axial length. To determine the imaging characteristics and genetic information (CTG repeat numbers) that were associated with the z-Evans Index, we used binominal logistic regression analyses. Results The z-Evans Index was significantly larger in the patients than in the controls (0.30 ± 0.05 vs. 0.24 ± 0.02; p Conclusions Our MRI study revealed a normal pressure hydrocephalus (NPH)-like appearance as a morphologic finding accompanied by ventriculomegaly in DM1 that tends to occur in elderly patients.

Myotonic dystrophy type 1 (DM1) is the most common form of muscular dystrophy in adults, affecting multiple organs, including the eyes, heart, endocrine system, and central nervous system. The broad spectrum of DM1 symptoms has been attributed to the aberrant pre-mRNA splicing of various genes due to an abnormal expansion of the CTG repeat in the 3' untranslated region of the DMPK gene. The current challenge in the clinical care of DM1 is the lack of well-established protocols for the management of each organ disorder or symptom. Moreover, the current status of clinical management has not been adequately explored. Metabolic disturbance in DM1 has been less explored among the DM1 manifestations, even though impaired glucose tolerance is a widely known metabolic disorder associated with DM1. We investigated the metabolic disturbance related to DM1 using the national registry of neuromuscular diseases in Japan, Registry of Muscular Dystrophy (Remudy), and assessed the metabolic complications in DM1 and the current treatments. We obtained comprehensive information on the current status of liver dysfunction and dyslipidemia in a sizeable DM1 cohort (~300). We confirmed that the incidence of liver dysfunction and dyslipidemia, particularly hypertriglyceridemia, as well as impaired glucose tolerance, were significantly higher in DM1 patients. Furthermore, the majority of DM1 patients with dyslipidemia were not receiving pharmacotherapy. Our data highlight the current status of DM1 patients in Japan, which can guide the establishment of the standard of care for metabolic issues consequent to DM1.

BackgroundMyotonic dystrophy type 1 involves cardiac conduction disorders. Cardiac conduction disease can cause fatal arrhythmias or sudden death in patients with myotonic dystrophy type 1.Methods and ResultsThis study enrolled 506 patients with myotonic dystrophy type 1 (aged ≥15 years; >50 cytosine‐thymine‐guanine repeats) and was treated in 9 Japanese hospitals for neuromuscular diseases from January 2006 to August 2016. We investigated genetic and clinical backgrounds including health care, activities of daily living, dietary intake, cardiac involvement, and respiratory involvement during follow‐up. The cause of death or the occurrence of composite cardiac events (ie, ventricular arrhythmias, advanced atrioventricular blocks, and device implantations) were evaluated as significant outcomes. During a median follow‐up period of 87 months (Q1–Q3, 37–138 months), 71 patients expired. In the univariate analysis, pacemaker implantations (hazard ratio [HR], 4.35; 95% CI, 1.22–15.50) were associated with sudden death. In contrast, PQ interval ≥240 ms, QRS duration ≥120 ms, nutrition, or respiratory failure were not associated with the incidence of sudden death. The multivariable analysis revealed that a PQ interval ≥240 ms (HR, 2.79; 95% CI, 1.9–7.19,PP< 0.01) were independent factors associated with a higher occurrence of cardiac events than those observed with a PQ interval ConclusionsCardiac conduction disorders are independent markers associated with cardiac events. Further investigation on the prediction of occurrence of sudden death is warranted.

Background Multi-systemic symptoms of varying severity in myotonic dystrophy type 1 (DM1) may pose difficulties in caregiving. However, the factors which affect their care burden are yet to be sufficiently understood. Objective We investigated care burden and its correlates among caregivers of patients with DM1. Methods General demographic information was obtained from patients with DM1, as well as Barthel index (ADL), body mass index, and genetic information. Patients completed SF-36v2 (health-related quality of life), CES-D (depressive symptoms), and ESS (daytime sleepiness) questionnaires. Caregivers reported their perception of patient's status through these questionnaires, and completed Zarit Caregiver Burden Interview (ZBI). Correlation analysis of these variables were performed, and regression analysis was utilized to assess the relationship between caregiver burden and other variables. Results Forty-three patient-caregiver dyads participated. Mean ZBI score was 20.7±17.4, and 32.6% reported a significant care burden. ZBI correlated with caregiver-reported CES-D, but not with patient-reported CES-D. Both patient-reported and caregiver-reported physical QoL of patients correlated with patient ADL. Multiple regression analysis revealed that the combination of caregiver-reported CES-D, caregiver-reported mental QoL, and genetic characteristics predicted caregiver burden. Conclusions Caregiver burden was felt although patients were relatively well-functioning. Patients' and caregivers' assessment of patients' physical condition were similar. However, they did not agree on the evaluation of the patients' psychological state. Cognitive characteristic of the patients and the caregivers' perception of the patients' state may have affected the results. Future DM1 care strategies need to work on improvement of patient-caregiver communication and provide support for the caregiver's psychological health.

To compare central conduction in ulnar and median nerve somatosensory evoked potentials (SEPs), we recorded SEPs from the neck and scalp elicited by median and ulnar nerve stimulation in 46 normal young adults.We determined the central conduction time (CCT) in each subject from peak-to-peak and onset-to-onset measurements. The mean value of the onset CCT for the ulnar nerve SEP was 6.2 +/- 0.3 msec, and for the median nerve SEP, 5.9 +/- 0.3 msec. Onset CCT was significantly longer for the ulnar nerve SEP, and there was a significant correlation between onset CCT in both median and ulnar nerve SEPs and subject height. In contrast, the mean value of the "conventional" peak CCT for the ulnar nerve SEP was 5.6 +/- 0.6 msec, and for the median nerve SEP, 5.8 +/- 0.5 msec, with no significant difference between them. In addition, the peak CCT was not correlated with subject height in the ulnar or median nerve SEPs. Our findings suggest that onset CCT measurement is superior to the conventional peak CCT measurement for ulnar as well as median nerve SEPs, and confirm that the central conduction pathway for the ulnar nerve SEP is slightly longer than that for the median nerve SEP.NEUROLOGY 1996;47: 1299-1304

Insulin resistance is a characteristic feature of glucose intolerance in myotonic dystrophy type 1 (DM1). DM1 patients with dysglycaemia have liver insulin resistance as well as muscle insulin resistance, and also abnormality of insulin secretion. Insulin resistance in DM1 might result in multiple metabolic defects. Low level of fasting plasma glucose is a characteristic feature in the early stage of glucose intolerance in DM1, Early intervention against insulin resistance in DM1 is suggested because glucose intolerance could deteriorate in a certain degree of cases. Metformin treatment is useful to improve insulin resistance in DM1. Diabetic patients with DM1 usually show mild hyperglycemia. However, poorly controlled patients with hyperglycemic pattern tending to rise from morning to evening exist. Intensive insulin therapy might be necessary in such cases. We should pay attention to hypoglycemia due to hyperinsulinemia, pseudo improvement of glucose control according to exacerbated dysphagia, and acute aggravation caused by infections, at a bedside.

✓ Epidermal growth factor (EGF) content in urine from patients with glial tumors was examined by radioimmunoassay techniques with labeled human EGF and its rabbit EGF polyclonal antibody. There was no cross-reaction with transforming growth factor-α, which has a common receptor with EGF. Forty glial tumors were divided into three groups according to the clinical stage: Samples from Group A patients were obtained before therapy and/or after biopsy; in these patients a large volume of tumor was apparent on computerized tomography (CT). Group B samples were obtained after gross total removal of the tumor and/or chemo- and radiation therapy; these patients showed a small volume of residual tumor on CT. Samples from Group C patients were obtained after gross tumor total removal and/or chemo- and radiation therapy; no tumor was detected on CT scans in these patients. Urinary EGF levels in Group A samples were statistically significantly higher than in samples from healthy individuals (p < 0.001), Group B patients (p < 0.10), and Group C patients (p < 0.02). In addition, high-grade glial tumors in Group A cases showed a significantly higher level of urinary EGF than low-grade tumors in Group A patients (p < 0.05), or patients with meningioma (p < 0.02), metastatic brain tumor (p < 0.05), and cerebral infarction (p < 0.001). Longitudinal changes of urinary EGF levels in glioma patients mostly synchronized with the clinical course and therapeutic interventions. Therefore, urinary EGF, as a glial tumor marker, may be of practical value for diagnosing a malignant glioma and evaluating for the efficacy of chemo- and radiation therapy.

Using positron emission tomography (PET), cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMR02) were measured in 32 healthy volunteers aged from 27 to 67 years. In bilateral putamen, left supratemporal\ left infrafrontal and left parietal cortices, CMR02 showed a significant decline during aging. The age-related decline of CBF was seen only at the left superior temporal cortex. The mean CMR02 was significantly lower in the elder group (over 51 years old) than in the younger group (under 50 years old), whereas no significant difference in mean CBF between the two groups. The poor correlation of CBF to the age could be explained partly by the fact that CBF is easily influenced by the physiological, psychological and/or environmental factors. The age-related changes of CMR02 were more marked in the association cortices of the left hemisphere than in that of the right hemisphere.

Background Magnetic resonance–guided PLDD has been performed for patients with single-level contained focal disk herniation. We investigated the clinical results of our PLDD practice in reference to the site of the needle tip. Methods Thirty-two patients (24 male patients and 8 female patients; mean age, 35 years) who presented with low back pain and signs of monoradiculopathy underwent MR-guided PLDD. The final location of the needle tip was plotted on a T 1 -weighted axial plane of the targeted disk. An axial image of the targeted disk was divided into 4 quadrants in a cruciform fashion and into 3 zones in a concentric circle. The clinical results as evaluated by MacNab's criteria 6 months after PLDD were investigated in each subdivided area where the needle tip was located. Results The overall success rate of our PLDD practice was 68.8%. The success rate in the 27 patients who had the needle tip in the DL quadrant of the targeted disk was 70.4%. Among them, 14 patients who had the needle tip in the middle zone showed a favorable outcome (77.8%). Conclusions The final location of the needle tip was demonstrated in all cases. Although our MR imaging study was not sufficient to determine the exact position of the needle tip because of MR image distortion, such error seems to be acceptable in the results of our study obtained from the relative positioning of the needle tip in the disk space. This study suggests that the middle zone in the DL quadrant of the targeted disk space seems to be a favorable target to obtain better clinical outcomes.

To study the correlation between somatosensory central conduction time (CCT) and the subject's height, we recorded somatosensory evoked potentials (SEPs) from the neck and scalp elicited by median nerve stimulation in 72 normal young adults. We determined the CCT in each subject from peak-to-peak and onset-to-onset measurements. The mean value for the onset CCT was 6.2 +/- 0.4 msec and for the peak CCT, 5.7 +/- 0.5 msec. The peak CCT was significantly shorter but showed a wide range. There was a significant correlation between the onset CCT, but not the peak CCT, and height. Our findings confirm that the length of the central somatosensory pathway is proportional to the subject's height and indicate that the "conventional" peak CCT measurement of median nerve SEPs is inadequate.