Peripheral neuropathy in myotonic dystrophy type 1

Myotonic dystrophy 1 (DM1) is characterized by a wide range of clinical features. We aimed to verify the presence of peripheral nerve involvement in a large cohort of DM1 patients and to determine clinical consequences. A total of 93 patients underwent detailed neurological examination and nerve conduction studies. Additionally, balance impairment was assessed with the Berg Balance Scale and health status was evaluated with the SF-36 health survey. Sensory symptoms were not reported and mild sensory signs were found in six patients. Electrophysiological abnormalities consistent with a diagnosis of neuropathy were found in 16 patients (17%). Peripheral nerve involvement was significantly associated with decreased muscle strength (p = 0.001) and absence of Achilles-tendon reflexes (p = 0.003), but not with age or duration of neuromuscular symptoms. It had no significant effect on balance, mental or physical health. In conclusion, peripheral nerve involvement may be one of the multisystemic manifestations of DM1, but is usually subclinical. Other causes should be excluded when sensory symptoms or signs are severe.     

Sarcolemmal excitability in myotonic dystrophy: Assessment through surface EMG

A motor point stimulation protocol was carried out on the tibialis anterior of myotonic dystrophy (MyD) patients. The surface myoelectric signal was monitored to record average rectified value (ARV), median frequency of power spectrum (MDF), and conduction velocity (CV) parameters. The ARV curve showed a decreasing trend that reveals a reduction in the M-wave amplitude during stimulation. MDF presented a significant decrement in the first seconds of sustained contraction, probably caused by abnormal lengthening of the depolarization zone. CV was significantly lower in patients, suggesting reduced mean fiber size. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:543–546, 1998.     

Central and peripheral components of exercise-related fatigability in myotonic dystrophy type 1

Boërio D, Lefaucheur J‐P, Bassez G, Hogrel J‐Y. Central and peripheral components of exercise‐related fatigability in myotonic dystrophy type 1.
Acta Neurol Scand: 2012: 125: 38–46.
© 2011 John Wiley & Sons A/S. Background – Fatigue frequently occurs in myotonic dystrophy type 1 (DM1), but its pathophysiology remains unclear. This study assessed central and peripheral components of exercise‐related fatigability in patients with DM1, compared to controls. Methods – Examinations were performed before and after a contraction of the abductor digiti minimi (ADM) muscle sustained for 45 s at 60% of maximal voluntary contraction (MVC). Myoelectric activity was recorded using high spatial resolution surface EMG during twitch stimulations and MVC and was characterized by root mean square, mean power frequency (MPF), and muscle fiber conduction velocity (MFCV). Peripheral nerve excitability was assessed by stimulating the ulnar nerve at the wrist with ADM recordings. Motor cortex excitability testing to transcranial magnetic stimulation included measures of intracortical facilitation and inhibition of motor evoked potentials (MEPs) in ADM muscle. Results – At baseline, patients with DM1 showed altered peripheral nerve and cortical excitability (reduced intracortical facilitation) associated with impaired myoelectric properties. During the fatiguing exercise, the force remained stable, while MPF and MFCV decreased in both DM1 and control groups. After exercise, only refractoriness was reduced in patients with DM1, whereas controls showed marked neuromuscular and cortical changes. Conclusion – Patients with DM1 showed altered excitability of various cortical and neuromuscular components at baseline. However, most of excitability parameters did not vary after exercise in patients with DM1, in contrast to controls. This suggests that excitability properties, frankly altered at baseline, were not prone to be affected further after exercise in patients with DM1.     

Axonal motor and sensory neuropathy in myotonic dystrophy

We report the neurophysiological findings from 24 subjects with myotonic dystrophy of Steinert and the histological findings in two of them. The conduction data is compared with that of a group of subjects with Landouzy-Déjérine muscular dystrophy. In 46% of cases, the electrophysiological data revealed slight and generalized axonal neuropathy. Histological results of sural nerve confirmed axonal damage of sensory fibres. The neuropathy was not correlated with age of patients, duration or onset of the disease, nor with the state of the deep reflexes; it did not show signs of progressing and is probably one of the multisystemic manifestations of gene pleiotropism.     

Axonal excitability in primary amyloidotic neuropathy

Introduction: Acquired and hereditary amyloidosis can cause peripheral neuropathy, but the mechanisms by which this occurs have not been established. Threshold tracking techniques allow in vivo assessment of the properties of the axonal membrane and may shed light on pathogenetic mechanisms underlying neuropathic disorders. Methods: We studied 10 subjects with primary amyloidosis using conventional nerve conduction studies and quantitative sensory, autonomic, and axonal excitability testing of median motor and sensory fibers. Results: As expected, subjects with amyloidosis had evidence of small‐ and large‐fiber neuropathy on conventional testing. There was no significant difference in axonal excitability between subjects and controls apart from the stimulus required to activate sensory fibers. Conclusions: Amyloid‐related neuropathy does not produce a change in membrane potential as either a primary or secondary event. This suggests that ischemia and axonal compression are unlikely mechanisms for the neuropathy. Muscle Nerve 51: 443–445, 2015     

Absent,unrecognized, and minimal myotonic discharges in myotonic dystrophy type 2

The purpose of this study was to describe the frequency of absent, unrecognized, or minimal myotonic discharges (MDs) in myotonic dystrophy type 2 (DM2). We performed a retrospective review of needle electromyography (EMG) data prior to genetic diagnosis in 49 DM2 patients at the Mayo Clinic. MDs were not reported on first or repeat EMG studies (n = 8) and not found in archived recordings of 4 patients (8%); archived EMG recordings (n = 4) confirmed the absence of MDs (n = 2), including 1 patient with normal insertional activity in all muscles, and misinterpretation of MDs as slow fibrillation potentials (n = 1) and complex repetitive discharge (CRD) activity (n = 1). Eight (16%) patients had minimal classic MDs with diffusely increased insertional activity, including waning‐only MDs in all patients in this group with archived EMG recordings (n = 5). Diffuse MDs were found in 33 (67%) patients. Absent or minimal MDs do not exclude DM2. Over‐reliance on diffuse MDs in patients who present with myopathy may lead to delay in genetic diagnosis of DM2. Muscle Nerve, 2010     

强直性肌营养不良症的临床特点

目的总结强直性肌营养不良症(DM)的临床特点。方法回顾性分析24例DM患者的临床资料。结果本组中20例(83.3%)患者在青年期起病,进展缓慢;19例(79.2%)有家族史。临床表现以面部、颈部及肢体远端肌肉为主的无力、萎缩及强直,伸肌重于屈肌;可伴全身多系统受累;血清肌酶正常或轻度升高。肌电图具有特征性的肌强直放电和肌源性损害;8例肌肉病理检查显示核内移、核链形成,以Ⅰ型肌纤维萎缩为主,7例出现肌纤维坏死,4例肌纤维结构紊乱,3例肌浆块,2例肌膜呈锯齿状。结论DM的临床特征是肌无力、萎缩及强直;肌电图和肌活检对诊断具有重要意义。     

Bone anomalies in myotonic dystrophy

Sixteen patients with myotonic dystrophy underwent CT examination of the skull, and measurement of bone mineral density at lumbar spine and hip by dual-photon absortiometry. The results were compared with those of 20 normal subjects of similar age and sex distribution. Hyperostosis of the calvarium, and increased bone mineral density at lumbar vertebrae were observed. One case showed basal ganglia calcification associated with hyperparathyroidism secondary to deficiency of vitamin D. In the other 15 patients, studies of calcium metabolism were normal. There results suggest the existence of generalized hyperostotic potential in patients with myotonic dystrophy.     

强直性肌营养不良临床特点分析

目的分析强直性肌营养不良(DM)的临床特点,以提高对DM疾病的认识及诊断水平。方法对21例DM患者的临床资料进行回顾性总结与分析。结果 21例患者均为慢性起病,以双手无力,活动不灵活起病多见,其中5例有家族史,部分病例伴有心脏、眼部、内分泌及中枢神经系统等其他多系统损害。19例行肌电图检查提示肌源性损害,其中16例发现有肌强直电位。10例行肌活检,主要表现为部分肌纤维萎缩,变性、坏死肌纤维,核内移及肌浆块形成,部分萎缩纤维内可见无结构胞浆体。1例强直性肌营养不良蛋白激酶(DMPK)基因CTG重复序列分析发现拷贝数超过正常范围。结论 DM是一种主要累及肌肉系统,以肌强直、肌无力和肌萎缩为主要临床表现并伴有多系统损害的疾病。综合评估多系统损害并结合肌肉的电生理学及病理学检查,有助于提高对DM的认识;在有条件的医疗机构可以开展DM基因诊断,对DM确诊很有意义。     

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.     

Sarcolemmal excitability in the myotonic dystrophies

Introduction: Chloride conductance disturbances contribute to sarcolemmal dysfunction in myotonic dystrophy type 1 (DM1) and type 2 (DM2). Studies using muscle velocity recovery cycles (MVRCs) suggest Na⁺/K⁺‐adenosine triphosphatase activation becomes defective in advanced DM1. We used MVRCs to investigate muscle excitability in DM1 and DM2. Methods: MVRCs were measured for patients with mild (n = 8) and advanced (n = 11) DM1, DM2 (n = 4), and normal controls (n = 30). Results: Residual supernormality after multiple conditioning stimuli was increased in DM2 and advanced DM1. Advanced DM1 was distinguished by increases in muscle relative refractory period (MRRP) and reduced early supernormality as well as peak amplitude decrements for the first and last responses in train during repetitive stimulation. Discussion: Prolongation of the MRRP indicates that depolarization of the resting muscle membrane potential occurs in advanced DM1, with possible implications for future therapeutic approaches. Muscle Nerve 57 : 595–602, 2018     

强直性肌营养不良症的临床与肌肉病理学特点

目的探讨强直性肌营养不良症(DM)的临床及肌肉病理学的特点。方法对6例DM患者的临床资料进行回顾性分析。结果6例患者均呈慢性病程,以肌无力、肌强直和肌肉萎缩为主要表现,多伴有脱发、白内障、心脏传导阻滞等多系统损害。肌电图检查结果为肌源性损害,6例均可见肌强直电位发放。病理学检查见肌纤维核内移、核袋及核链现象,部分患者可见肌质块及肌纤维分布异常。结论DM是一种以肌无力和肌强直为主要表现的多系统损害的遗传性疾病;特征性病理改变为肌纤维核内移、核链以及肌质块、肌纤维分布异常。     

Falls and stumbles in myotonic dystrophy

OBJECTIVE: To investigate falls and risk factors in patients with myotonic dystrophy type 1 (DM1) compared with healthy volunteers. METHODS: 13 sequential patients with DM1 from different kindreds were compared with 12 healthy volunteers. All subjects were evaluated using the Rivermead Mobility Index, Performance Oriented Mobility Assessment, and modified Activities Specific Balance Confidence scale. Measures of lower limb muscle strength, gait speed, and 7-day ambulatory activity monitoring were recorded. Subjects returned a weekly card detailing stumbles and falls. RESULTS: 11 of 13 patients (mean age 46.5 years, seven female) had 127 stumbles and 34 falls over the 13 weeks, compared with 10 of 12 healthy subjects (34.4 years, seven female) who had 26 stumbles and three falls. Patients were less active than healthy subjects but had more falls and stumbles per 5000 right steps taken (mean (SD) events, 0.21 (0.29) v 0.02 (0.02), p = 0.007). Patients who fell (n = 6) had on average a lower Rivermead Mobility score, slower self selected gait speed, and higher depression scores than those who did not. CONCLUSIONS: DM1 patients stumble or fall about 10 times more often than healthy volunteers. Routine inquiry about falls and stumbles is justified. A study of multidisciplinary intervention to reduce the risk of falls seems warranted.     

Peripheral Nerve Axon Involvement in Myotonic Dystrophy Type 1, Measured Using the Automated Nerve Excitability Test

Background and Purpose

Primary involvement of the peripheral nerves in myotonic dystrophy type I (MyD1) is controversial. We investigated whether the involvement of peripheral nerves is a primary event of MyD1 or secondary to another complication such as diabetes mellitus (DM).

Methods

The subjects comprised 12 patients with MyD1, 12 with DM and no peripheral nerve involvement, and 25 healthy volunteers. We measured multiple excitability indices in the median motor axons. The strength-duration time constant was calculated from the duration-charge curve, the threshold electrotonus and current-threshold relationships were calculated from the sequential subthreshold current, and the recovery cycle was derived from double suprathreshold stimulation.

Results

The depolarizing and hyperpolarizing threshold electrotonus were significantly reduced and exhibited increased refractoriness in the MyD1 group compared with the DM and control groups. The SDTC, superexcitability, and subexcitability were not significantly altered in the MyD1 group.

Conclusions

The MyD1 group exhibited a depolarized axonal membrane potential. The significant differences in peripheral nerve excitability between the MyD1 group and the DM and normal control groups suggest that peripheral neuropathy is a primary event in MyD1 rather than a secondary complication of DM.