Autonomic nervous system function in myotonic dystrophy

Symptoms suggestive of dysautonomia are often reported in Myotonic Dystrophy (MD) patients. 12 patients with MD underwent cardiovascular function testing with assay of plasma noradrenaline (NA) and adrenaline (A) in supine rest condition and after orthostatic and cold stimulus. Statistical analysis showed no differences between MD patients and an age and sex matched control group.

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Sommario Nei pazienti affetti da Distrofia Miotonica si riscontrano spesso sintomi che suggeriscono un'alterata funzione del Sistema Nervoso Vegetativo. Abbiamo sottoposto a valutazione dei riflessi cardiovascolari e dei livelli ematici di catecolamine (adrenalina e noradrenalina) in condizioni basali, in psizione supina e dopo lo stimolo ortostatico e cold-pressor 12 pazienti affetti da Distrofia Miotonica. L'analisi statistica dei dati non ha mostrato differenze fra i pazienti e un gruppo di controllo comparabile per sesso ed età.

     

Neurophysiological and radiological findings in myotonic dystrophy patients

Somatosensory evoked potentials (SEPs) and brainstem auditory evoked potentials (BAEPs) were recorded in 10 patients with myotonic dystrophy and in 20 sex and age-matched healthy controls. In all patients a brain MRI examination was also performed. In our results, the significantly longer absolute peak latencies of the SEPs and the abnormal increasing of the later components of the BAEPs suggest an involvement of the afferent sensory and central auditory pathways. Brain MRI showed white matter hyperintense lesions (WMHL) in eight patients (80%). No correlations were found between individual abnormal electrophysiological parameters or severity of WMHL and age, age at onset, disease duration or muscular impairment. The total number (SEP + BAEP) of electrophysiological abnormalities significantly correlated with muscular impairment ( p < 0.05) and MRI changes ( p < 0.05), suggesting a strict pathogenetic linkage between muscular and nervous system alterations in this disease.     

Multimodality evoked potentials in amyotrophic lateral sclerosis

Visual, brainstem auditory and somatosensory evoked potentials to medial nerve stimulation were recorded in 27 patients affected by amyotrophic lateral sclerosis. VEP N75, P100, N140, N75-P100 latencies and P100 amplitude, BAEP I-III, III-V and I-V interpeak-latencies were within normal limits in all ALS patients. Somatosensory evoked potentials were abnormally delayed in 8 patients: in 3 arms because of a delayed N9-N13 latency, in 9 arms because of a delayed N13-N19 latency.     

Event-related potentials (P300) in myotonic dystrophy

The P300 component of the auditory event-related potential in 8 patients with myotonic dystrophy was studied and compared with that of 13 healthy controls. Abnormalities of P300 (prolongation of the latency and/or decrease of the amplitude) were observed in 6. These observations imply that the function of cognitive and information processing are impaired in myotonic dystrophy.     

5例强直性肌营养不良一家系报道

1病例 先证者,女性,35岁,6年余前渐出现梳头困难,活动后加重,病情渐进展,持物费力,行走困难,不能耐受活动。既往：无特殊表现。查体：体重46kg,面容瘦长,颧骨突出,呈斧状脸,构音稍含糊,双眼睑闭合力弱,颈项部、胸背部及四肢近远端明显肌萎缩,肌肉叩诊未见肌球;四肢肌张力低,颈项肌肌力2级,四肢肌力4级,用力握拳后不能立即将手伸开、重复数次后才能放松;     

Myopathology of myotonic dystrophy

Summary A histometric analysis of 16 biopsies taken from patients with myotonic dystrophy predominantly revealed type 1 atrophy, type 1 and 2 hypertrophy and type 1 predominance. These changes do not occur in all biopsies and are not pathognostic.Under the electron microscope otherwise apparently normal muscle fibres often demonstrated a single change: a swelling and proliferation of the sarcoreticulotubular system in the I-band region. Morphometry of randomly selected fibres from 15 biopsies revealed a significant increase in the sarcotubular membrane profile concentration in longitudinally and in transversally oriented sections. In addition, a shifting and disappearance of thin filaments in the I-band was noted to be an early sign. Pathological changes in the plasma membrane such as excessive foldings, expulsion of vesicular material and periodic densities were also seen. The morphometric analysis did not reveal any significant change in the mitochondrial fraction and mean mitochondrial size. All the ultrastructural changes of skeletal muscle decribed in myotonic dystrophy are unspecific. Even the alterations of the plasma membrane and the sarcoreticulotubular system described here may not be a primary correlate to myotonia, but represent secondary alterations or may belong to the dystrophic changes. Spontaneous human and experimental myotonia may exist without such alterations.Some biopsies demonstrated light and electron microscopic findings which may indicate a neurogenic process. However, it appears more probable that both the nerve and the muscle may be independently affected by the pleiotropic action of the responsible gene.     

Skeletal muscle changes associated with equine myotonic dystrophy

Summary A progressive neuromuscular disorder in young horses, clinically apparent as early as 1 month of age, is characterized by generalized myotonia, muscle stiffness, muscle weakness and atrophy. Myotonia is identified by percussion dimpling and myotonic EMG discharges. Changes in one case included testicular hypoplasia, cataract formation, and glucose intolerance, indicating a systemic involvement. Pathologic changes in skeletal muscles from three affected foals were examined. Sarcoplasmic masses, ringed fibers, internal positioning of sarcolemmal nuclei, and nuclear rowing were among the primary histologic changes noted. Variation in fiber diameter size, especially atrophy, and type I predominance were also prominent changes. A neurogenic involvement was indicated by type grouping changes in several muscles.Supported in part of Washington State University, the Equine Orthopedic Research Fund, and NIH grant RR00515     

Multimodality evoked potentials in HIV infected subjects: A longitudinal study

18 subjects with symptomless HIV infection were investigated with multimodal evoked potentials for possible CNS involvement and again after an 8–12 month interval. 13 subjects showed neuropsychological changes, which were confirmed at the second examination. The 5 subjects found normal remained so at the second examination. On WAIS assessment the only patient to earn pathological scores was the one with the greatest evoked potentials changes. Thus the evoked potentials procedure proved capable of identifying early CNS involvement by HIV infection.

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Sommario Diciotto soggetti affetti da infezione da HIV in fase asintomatica sono stati studiati con Potenziali Evocati Multimodali per indagare l'eventuale coinvolgimento del S.N.C. Lo studio è stato ripetuto a 8–12 mesi di distanza. In 13 soggetti sono state evidenziate alterazioni neuropsicologiche confermate dal successivo controllo. I 5 soggetti risultati normali alla I registrazione si sono conservati tali alla registrazione successiva. I pazienti sono stati valutati anche con la WAIS. L'unico soggetto che ha presentato punteggi patologici era quello con maggiori alterazioni dei potenziali evocati. La metodica dei potenziali evocati si è mostrata capace di individuare il precoce interessamento del S.N.C. nell'infezione da HIV.

     

Daytime somnolence in myotonic dystrophy

Somnolence in myotonic dystrophy (DM) has not been measured using a reliable daytime somnolence scale. The aim of this study was to compare somnolence in DM patients with healthy controls and Charcot-Marie-Tooth disease (CMT) patients using such a scale and to compare this with potential contributory factors. We investigated 35 subjects with adult-onset DM, 16 healthy controls and 13 CMT controls. The Epworth Sleepiness Scale (ESS) was the principal measurement of daytime somnolence. Nocturnal sleep was assessed using a sleep diary. Other assessments measured daytime respiratory function, cognitive function, motor impairment, disability, swallowing capacity and depression. DM and CMT patients had greater daytime sleepiness than unaffected controls. In the DM group significant correlations were found between somnolence and measures of disability, sleep quality and some measures of depression. It was concluded that there is an abnormal level of daytime somnolence in DM, which is partially associated with disability. Received: 2 March 1998 Received in revised form: 14 July 1998 Accepted: 4 August 1998     

Sleep-related breathing impairment in myotonic dystrophy

Summary Respiratory failure has been described in myotonic dystrophy; it worsens during sleep but its central or peripheral origin has yet to be determined. Moreover, patients may present severely disturbed sleep and daytime somnolence. Eight patients with mild to moderate myotonic dystrophy were studied to assess breathing function while awake and during sleep by means of the pulmonary function tests, nocturnal polysomnographic examination and the multiple sleep latency test (MSLT). Three patients had restrictive respiratory defects; none had signs of airway obstruction. All patients had very disrupted nocturnal sleep. Of six patients who underwent the MSLT only two showed a mild tendency to sleep during the day. Six patients had pathological apnoea plus hypopnoea index [(A+H)I] and there was a prevalence of central apnoeas. The apnoeas occurred while resting but awake and throughout all sleep stages. Only two patients (the ones with the least vital capacity) had episodes of progressive oxygen desaturation during rapid eye movement sleep, similar to those found in other restrictive disorders and in chronic obstructive pulmonary disease. It is concluded that the breathing pattern characteristic of our myotonic dystrophy patients was the occurrence of central apnoeas both at rest while awake and during sleep.     

DM基因CTG重复数与BAEP、SEP、VEP对比分析

目的：探讨强直性肌营养不良（DM）患者及其家系成员三核苷酸重复数CTG（胞嘧啶、胸腺嘧啶、乌嘌呤）的变化与脑干听觉诱发电位（BAEP）、体感诱发电位（SEP）、视觉诱发电位（VEP）的关系。方法：用聚合酶链（PCR）扩增及DNA杂交法对5例临床诊断DM患者及其中三个家系的16名成员进行DM基因的CTG重复数和BAE、SEP和VEP测定。结果：10名正常人CTG重复数是30个,BAEP、SEP、VEP正常;5例DM病人CTG重复数均在85个以上,其中2列在1605个以上,明显高于正常人;16例家系成员中除4例正常,余12例CTG重复数均超过正常基因,而且,CTG重复数与临床症状、BAEP、SEP、VEP轻重有关。结论DM基因诊断有其临床症状、BAEP、SEP、VEP改变相一致。     

Treatment of myotonic dystrophy with acetazolamide

Summary This report describes a patient with myotonic dystrophy who had severe action and percussion myotonia. The patient was unresponsive to diphenylhydantoin therapy. Treatment with acetazolamide, 250 mg daily, decreased the myotonia markedly. A possible mechanism of the favorable effect of acetazolamide in myotonia is discussed.

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Zusammenfassung Es wird ein Patient mit Dystrophia Myotonica beschrieben, der eine sehr ausgeprägte Myotonie nach aktiver Muskelkontraktion und Muskelperkussion aufwies. Er reagierte nicht auf eine Diphenylhydantoinbehandlung. Eine Therapie mit Acetazolamide, 250 mg täglich, bewirkte eine deutliche Verminderung der myotonen Reaktion. Es wird der mögliche Wirkungsmechanismus des Acetazolamides bei der Myotonie diskutiert.

     

Respiratory dysfunction in myotonic dystrophy type 1: A systematic review

Myotonic dystrophy type 1 (DM1) is one of the most common muscular dystrophies in adults. This review summarises the current literature regarding the natural history of respiratory dysfunction in DM1, the role of central respiratory drive and peripheral respiratory muscle involvement and its significance in respiratory function, and investigates the relationship between genetics (CTG repeat length) and respiratory dysfunction. The review included all articles that reported spirometry on 10 or more myotonic dystrophy patients. The final review included 55 articles between 1964 and 2017. The major conclusions of this review were (1) confirmation of the current consensus that respiratory dysfunction, predominantly a restrictive ventilatory pattern, is common in myotonic dystrophy and is associated with alveolar hypoventilation, chronic hypercapnia, and sleep disturbance in the form of sleep apnoea and sleep related disordered breathing; (2) contrary to commonly held belief, there is no consensus in the literature regarding the relationship between CTG repeat length and severity of respiratory dysfunction and a relationship has not been established; (3) the natural history and time-course of respiratory functional decline is very poorly understood in the current literature; (4) there is a consensus that there is a significant involvement of central respiratory drive in this alveolar hypoventilation however the current literature does not identify the mechanism for this.     

Neuropsychological profile in myotonic dystrophy

Summary Twenty patients with myotonic dystrophy underwent neuropsychological evaluation. Performances were analysed with respect to general cognitive profile, family patterns of cognitive impairment, relation with sex, age, extent of muscular involvement, and sex of affected parent. Results showed severe intellectual deficit in 50% of patients and selective impairment of visuospatial and constructional functions. Female patients showed significantly worse global intellectual status than males. No difference in intellectual level was observed in patients with respect to age, extent of muscular involvement and sex of affected parent. No family pattern of cognitive impairment could be identified. Our results show that an extensive neuropsychological battery can reveal the existence of selective mental impairment. It may provide further data on cognitive impairment onset, progression and relation to muscular involvement.     

Myasthenia gravis and thymoma coexisting with myotonic dystrophy type 1

We describe a 34-year old man presenting with subacute generalized myasthenic symptoms. His clinical features and laboratory investigations demonstrated both myasthenia gravis and myotonic dystrophy type 1. The computerized tomography of chest revealed anterior mediastinal mass. The lymphocyte-rich thymoma was removed surgically and he received radiotherapy. Recent observations suggested that the patients with myotonic dystrophy may have an increased risk of benign and malignant tumours but its coexistence with thymoma is very rare. The risk of thymoma associated with myotonic dystrophy is unknown.     

Developmental expression of myotonic dystrophy protein kinase in brain and its relevance to clinical phenotype

To investigate the pathophysiologic role of myotonic dystrophy protein kinase (DMPK) in the brain in myotonic dystrophy (MD), the developmental characteristics of DMPK immunoreactivity in the central nervous system and its alteration with disease were studied. Eleven patients’ brain with MD (5 congenital form, 6 adult form) were examined by immunohistochemistry using a specific antibody against synthetic DMPK peptides, anti-peptide DM1, and compared with 30 control brains, including 16 age-matched controls. In controls, DM1-immunoreactive neurons appeared in the early fetal frontal cortex and cerebellar granule cell layer, persisting through 29 weeks of gestation and then disappearing. In contrast, immunoreactive neurons continued to persist in the cerebral cortex and cerebellar granule cell layer of MD patients. When we counted DM1-immunoreactive neurons, the increase over controls was greater in the congenital form of MD than in the adult form, and was greater in the cerebrum than in the cerebellum in both forms of MD. DM1 immunostaining was predominantly nuclear, mirroring Western blotting of subcellular fractions. Differences in DM1 expression related to development and to the two forms of MD may be closely related to the pathogenesis of mental retardation in this disease. Received: 30 July 1999 / Revised: 21 January 2000 / Accepted: 1 February 2000     

Methylation of erythrocyte membrane phospholipid in patients with early-onset myotonic dystrophy

Methylation of erythrocyte membranes was compared in 10 patients with myotonic dystrophy (MyD) and sex- and age-matched healthy controls. The incorporation of 3H-methyl groups into phosphatidylcholine (PC) increased with age in the controls. In all 5 patients with early-onset MyD, 3H-methyl incorporation into PC was significantly higher than in sex- and age-matched controls. In contrast, 5 patients with adult form MyD showed incorporation rates into PC that were not significantly different from the controls. Our findings may confirm the presence of differences in the methylation of cellular membranes in MyD patients with the adult- and early-onset forms of the disease.     

Electrically-elicited surface mechanomyogram in myotonic dystrophy

The surface oscillation of the muscle during electrical stimulation is detectable by an accelerometer as a surface mechanomyogram (MMG). The aim of this study was to evaluate whether MMG properties reflect the mechanical muscle changes induced by myotonic dystrophy (MyD). To this end, the tibialis anterior of seven MyD patients and seven age- and sex-matched controls (C) was supramaximally stimulated at 1 (single twitches), 5, 10, 15, 20 Hz for 3 s at the most proximal motor point.Results Single twitches: The MMG amplitude was 67% less, the duration 37% longer, the electromechanical delay 64% longer, and the spectrum mean frequency 44% lower in the MyD patients than in controls.Repetitive stimulation At each stimulation frequency, the average MMG peak-to-peak was less in the MyD patients than in C.Conclusion The differences between the MMGs of MyD patients and C support the hypothesis that, together with the well-known changes in sarcolemmal excitability, an alteration in electromechanical coupling and a failure in contractile machinery may coexist in MyD.This work was supported by Telethon grant 740 and partly 1991 — Veicsteinas.     

强直性肌营养不良症19例骨骼肌病理分析

目的探讨强直性肌营养不良症(DM)骨骼肌病变的病理学特点。方法选择19例经临床和肌电图确诊的强直性肌营养不良症患者为研究对象,骨骼肌标本采用恒冷冰冻切片和酶组织化学染色方法,在光镜下观察骨骼肌组织的病理学变化特点。结果在HE染色,19例患者的骨骼肌标本均可见不同程度的肌纤维萎缩,但变性坏死肌纤维较少见,有7例患者在肌纤维中可见到肌质块。在组织化学MGT染色中,6例患者肌纤维中可见数量不等的破碎红边纤维(RRF),肌质块在MGT染色上呈深绿色,在NADH染色中肌质块呈深蓝色,较HE染色更易识别。在ATP酶染色中,19例患者有11例存在Ⅰ、Ⅱ型肌纤维分布异常现象,其中9例以Ⅰ型纤维明显占优势,2例以Ⅱ型纤维稍占优势,8例患者肌纤维分布基本正常。结论强直性肌营养不良症的骨骼肌病理改变,除常见的肌核增多内移,肌核聚集成核袋及核链现象以外,肌质块的出现和Ⅰ、Ⅱ型肌纤维分布异常应视为强直性肌营养不良症重要的特征性病理改变,肌肉活检对本病的诊断与鉴别诊断有一定的临床意义。     

强直性肌营养不良一家系临床分析

目的 探讨强直性肌营养不良(DM) 的临床特点,以提高对该病的认识.方法 对一DM 家系确诊的5例患者的临床资料进行收集分析,包括患者基本资料、临床表现、肌电图及肌肉活检等.结果 5例DM 患者均为慢性病程,以肌强直、肌无力、肌萎缩为主要表现,伴眼部、心脏、内分泌和神经等多系统损害,血清肌酶轻度增高或正常,肌电图具有特征性肌强直放电和肌源性损害,肌肉活检具有相对特异性肌病特征.结论 DM 是一种以肌强直、肌无力、肌萎缩为主要表现的多系统损害的遗传性疾病,临床表现复杂多样,肌肉活检有助于明确诊断.