Colchicine myopathy and neuropathy

Although colchicine has been used for centuries, its neuromuscular toxicity in humans is largely unrecognized. In this report we describe a characteristic syndrome of myopathy and neuropathy and present 12 new cases of the condition. Colchicine myopathy may occur in patients with gout who take customary doses of the drug but who have elevated plasma drug levels because of altered renal function. It usually presents with proximal weakness and always presents with elevation of serum creatine kinase; both features remit within three to four weeks after the drug is discontinued. The accompanying axonal polyneuropathy is mild and resolves slowly. Electromyography of proximal muscles shows a myopathy that is marked by abnormal spontaneous activity. Because of these features, colchicine myoneuropathy is usually misdiagnosed initially, either as probable polymyositis or as uremic neuropathy. The myopathy is vacuolar, marked by accumulation of lysosomes and autophagic vacuoles unrelated to necrosis or to the mild denervation in distal muscles. The morphologic changes in muscle suggest that the pathogenesis involves disruption of a microtubule-dependent cytoskeletal network that interacts with lysosomes. Correct diagnosis may save patients with this disorder from inappropriate therapy.     

Muscle fiber conduction velocity studied by the multi-channel surface EMG.

Muscle fiber conduction velocity in single motor unit (MU) during voluntary contraction was measured by using the multi-channel surface EMG. The subjects examined were 28 normal controls (5-40 years old), four patients with myopathy and three patients with neuropathy. The tibialis anterior and the biceps brachii muscles were investigated at weak and moderate contraction levels. In normal muscles, the mean muscle fiber conduction velocity increased with muscle force (P less than 0.01). In three of four cases with myopathy, the conduction velocities were reduced compared to normal subjects (P less than 0.01), and there was little or no correlation between the conduction velocity and muscle force in myopathy. The conduction velocities were within the normal range in the muscles of patients with neuropathy. However, high-amplitude MUAPs with fast conduction velocities were detected during weak voluntary contraction in one case with neuropathy.     

同型半胱氨酸、叶酸和维生素B12测定在糖尿病周围神经病变中的临床意义

探讨血浆同型半胱氨酸（Hcy）、叶酸（FA）和维生素B12（VitB12）测定在糖尿病周围神经病变中的临床价值。随机选择105例糖尿病患者,进行双下肢肌电图电生理检查,根据有无肌电图异常,分为单纯糖尿病组、糖尿病并发周围神经病变组,以健康成人作为正常对照组。分别采用荧光偏振免疫分析法和化学发光免疫分析法测定血浆Hcy和血清FA、VitB12。结果显示,与对照组及单纯糖尿病组相比,糖尿病周围神经病变组的血浆Hcy水平明显增高,血清FA和VitB12水平明显降低,两组间相比具有显著性差异（P〈0.01）。结论：高同型半胱氨酸血症是糖尿病周围神经病变的危险因素,而FA和VitB12的降低可能是诱发高同型半胱氨酸的重要因素,它们在糖尿病周围神经病变的发生发展过程中互为因果关系。     

Neuropathy in Wolfram syndrome

Wolfram syndrome (WFS) is a degenerative disease with neurological and endocrine disorders, characterized by the association of juvenile diabetes mellitus and bilateral optic atrophy. A polyneuropathy was exceptionally described but its characteristics are not well-established. In addition to our observation, we searched all case reports of patients with WFS in the medical literature (more than 600), and selected patients who underwent an EMG: twenty-one patients underwent an EMG, which was considered as abnormal in only 8 cases. The common profile was axonal sensory-motor polyneuropathy, sometimes with marked decrease of motor conduction velocities. This neuropathy could be due to diabetes mellitus, even though microangiopathic and macroangiopathic complications are rare in WFS. Another origin for this neuropathy could be a degenerative process in relationship with WFS.     

Four quantitative EMG methods and theirs individual parameter diagnostic value

Quantitative electromyography (EMG) usage in daily clinical medicine can exclude the investigation results influencing by the electromyographer's subjective factor in needle EMG. The aim of our study was to compare the diagnostic efficiency of these quantitative EMG methods which have found some more consistent application in routine neurologic practice. We have investigated 35 healthy subjects and 59 patients with two basic types of neuromuscular disorders (neuropathies and myopathies) by means of four quantitative EMG methods: 1--modified Buchthal's low threshold MUAPs (motor unit action potentials) analysis; 2--interference EMG pattern Dorfman's and McGill's limited decomposition; 3--interference EMG pattern spectral analysis; 4--interference EMG pattern turns-amplitude analysis. In results analysis parameter's 95% confidence intervals were calculated by Campbell and Gardner and the difference between three subject groups (controls, neuropathies, myopathies) was evaluated by special multidimensional statistics (Hotelling T2 test) using simultaneously all tested parameters of four quantitative EMG methods. The modified Buchthal's low threshold MUAPs analysis was the most effective method in discovering neuropathy and myopathy with area as the best discriminating parameter. The diagnostic power in neuropathies may be increased using selected quantitative EMG methods or theirs individual parameters combinations. Several aspects of applyied quantitative EMG methods and aquired data statistical analysis are discussed.     

Limb-girdle type muscular dystrophy in a large family with distal myopathy: homozygous manifestation of a dominant gene?

A family study was carried out to clarify the problem of two separate muscle disease phenotypes in a large consanguineous pedigree. These were a severe limb-girdle type muscular dystrophy and a mild late onset distal myopathy. Thirty-two first degree and 14 other relatives of 18 previously examined index patients were available for clinical examination. Twenty-three subjects underwent computed tomography of the lower leg muscles. No new cases of limb-girdle type muscular dystrophy were found. Distal myopathy was diagnosed in 14 subjects, 10 first degree relatives and four other relatives. Segregation analysis showed that the corrected proportion of affected with the severe proximal type was 0.246 and the proportion of affected with the distal myopathy was 0.58. Pedigree analysis is compatible with the possibility that the mild, late onset distal myopathy is caused by a dominant gene and that the limb-girdle type may be expressed in homozygotes.     

Hypertriglyceridemia may cause a subclinical peripheral neuropathy

Recently few patients with a painful neuropathy, attributed to extremely high triglyceride levels, were reported. In a prospective study, we evaluated 16 patients with marked hypertriglyceridemia without other causes of neuropathy, using nerve conduction and autonomic function tests. Six subjects (37%) showed mild signs of an asymptomatic motor and/or sensory and/or autonomic axonal polyneuropathy. The study demonstrates, that hypertriglyceridemia may be associated with a mild axonal polyneuropathy, usually subclinical, in significantly more patients than previously considered.     

Histopathologic study on muscle diseases among Koreans (274 muscle biopsy analysis)

All the diagnostic muscle biopsy cases were collected from the file of Department of Pathology, Seoul National University Hospital during June 1976 to December 1978. Slides were reviewed and correlated with clinical informations. Two hundred seventy four cases showed pathological changes, which were classified into six large groups (Table 1). Neurogenic atrophy was most common, 97 cases (35%), including 71 cases of motor neuron disease and 22 cases of peripheral neuropathy. Muscular dystrophy was seen in 92 cases (34%), and Duchenne type was the commonest among them (51 cases). Fifty seven cases showed inflammatory myopathy, making 20% of all cases. There were four cases of congenital myopathy and 13 cases showed various muscle diseases.     

Peripheral nerve amyloidosis in sural nerve biopsies: a clinicopathologic analysis of 13 cases

OBJECTIVE: Amyloidosis is a well-recognized but uncommon cause of peripheral neuropathy. Our objectives were to determine the overall prevalence of peripheral nerve amyloidosis in sural nerve biopsies and to evaluate the clinical and pathologic features of these lesions. METHODS: All available histologic and ultrastructural materials on biopsy tissue from 13 cases of peripheral nerve amyloidosis were examined. Muscle biopsies performed at the same time as the nerve biopsy were reviewed when available. Clinical data were collected on all patients. RESULTS: The prevalence of amyloidosis in sural nerve biopsies at our institution was 13 (1.2%) of 1098 cases over a 15.8-year period. These patients ranged in age from 41 to 82 years (median, 61 years) at initial presentation and included 10 men and 3 women. Presenting neuropathy symptoms were sensory in 6 of the 13 patients, motor in 2 cases, and mixed in 5 cases. Cardiac, renal, or gastrointestinal involvement was present in 7 of 13 cases. Two patients had myeloma and 7 had systemic autonomic symptoms. Two patients had probable familial amyloid polyneuropathy, and 1 patient demonstrated an alanine 60 point mutation. Amyloid, identified as amorphous eosinophilic extracellular deposits demonstrating apple green birefringence on Congo red stain or recognized by its characteristic fibrillar ultrastructure by electron microscopy, was identified in the endoneurium in 12 nerves, perineurium in 2 nerves, and epineurium in 9 nerves. Chronic inflammation was identified in 5 nerves. Axonal loss was recorded as mild (<25%) in 1 nerve, moderate (25% to 75%) in 8 nerves, and severe (>75%) in 4 nerves. Axonal degeneration predominated over demyelination in 8 of 10 cases that could be evaluated. Concomitant muscle biopsies contained amyloid deposits in 8 of 9 cases. CONCLUSIONS: Amyloidosis is a rare (1.2% in our series) cause of peripheral neuropathy with a distinct microscopic and ultrastructural appearance. Just over half the patients in our study had visceral organ involvement and systemic autonomic symptoms. The peripheral neuropathy was associated with axonal degeneration and a moderate to severe axonal loss in the majority of cases. Amyloid deposition was present in 8 out of 9 muscle biopsies performed at the same time.     

Miller Fisher syndrome: axonal, demyelinating or both?

Controversy exists concerning whether Miller Fisher syndrome (MFS) is the result of a predominantly axonal or demyelinating polyneuropathy and whether the Guillain-Barré syndrome variant of acute ataxia and areflexia without ophthalmoplegia, ataxic Guillain-Barré syndrome (atxGBS), has a distinct pathophysiology. We explored these issues by reviewing the electrophysiologic features of 6 patients with MFS and 2 patients with atxGBS. EMG laboratory records were reviewed and electrophysiologic findings were categorized as axonal or demyelinating neuropathy using previously defined criteria. Of the 6 patients with MFS, 5 had electrophysiologic evidence suggestive of an axonal, predominantly sensory polyneuropathy; only 1 patient met criteria for demyelinating polyneuropathy. Both patients with atxGBS had demyelinating sensorimotor polyneuropathy. Electrophysiologic abnormalities in MFS typically suggest a predominantly axonal, sensory polyneuropathy, though demyelinating forms occur and may be under-diagnosed using current criteria. AtxGBS, in our experience, is a predominantly demyelinating polyneuropathy.     

Determination of peak-ratio by digital turns-amplitude analysis on line

In a previous study the peak-ratio of turns to mean amplitude of the EMG interference pattern obtained from tape recordings identified 80% of patients with myopathy. In order to obtain the peak-ratio during the examination using the mean amplitude as an indication of force a digital turns-amplitude computer with a TMS 320/10 digital signal processor was developed. The EMG was analysed with a 12 bit resolution and a sampling rate of 100 kHz. In 492 samples from the brachial biceps muscle of controls, patients with myopathy and neuropathy, the digital method gave about the same turns-amplitude values as the analogue analyser. Control material for on line analysis of the peak-ratio was obtained in the brachial biceps, the abductor pollicis brevis, the medial vastus and the anterior tibial muscles of 20 subjects.     

Neuromuscular features in Marfan syndrome

Marfan syndrome is a clinically and allelic heterogeneous, heritable connective tissue disorder with infrequently reported neuromuscular features. This study is the first to delineate these symptoms in a non-selected population. Neuromuscular involvement was evaluated in 10 Marfan patients through a standardized questionnaire, physical examination, nerve conduction study (NCS), needle electromyography (EMG), muscle ultrasound, laboratory investigation, and muscle biopsy. Existing neuroimages were screened for dural ectasia and spinal meningeal cysts. Twenty healthy controls with similar age distribution completed the questionnaire.
The results showed that various neuromuscular symptoms occur more frequently in the patients. Four older patients reported muscle weakness, five patients had a mild-to-moderate reduction in vibration sense, and all older patients mentioned mild functional impairments. NCS showed axonal polyneuropathy in four and EMG myopathic and neurogenic changes in all patients. Increased echo intensity and atrophy on muscle ultrasound was found in more than half of the patients. Muscle biopsies obtained in two patients showed myopathic changes in the older, female patient.
In conclusion, the majority of Marfan patients exhibited neuromuscular symptoms characterized as myopathy or polyneuropathy or both, and signs of lumbosacral radiculopathy, with symptoms being most pronounced in the older patients. Although meriting corroboration, these findings indicate a need to further the awareness of neuromuscular involvement in this population.     

Lacunar dilatations of intrafusal and extrafusal terminal cisternae, annulate lamellae, confronting cisternae and tubulofilamentous inclusions within the spectrum of muscle and nerve fiber changes in myotonic dystrophy

In 3 out of 5 muscle spindles available in skeletal muscle biopsy specimens from 30 patients with myotonic dystrophy (MD) unusually large lacunar dilatations of terminal cisternae were observed that had thus far only been reported in extrafusal muscle fibers. Cytoplasmic annulate lamellae, confronting cisternae and regularly proliferated terminal cisternae, as well as intranuclear tubulovesicular inclusions were found in extrafusal muscle fibers that in combination with concentric membranous bodies seen in perineurial cells and Schwann cells generally emphasize an involvement of the endoplasmic reticulum in the pathogenesis of MD. In addition, a nuclear inclusion body was observed composed of tubulofilamentous structures with close similarity to those thought to be rather specific for inclusion body myositis. Vesicles filled with amorphous material originating from outer spindle capsule cells were suggested to indicate matrical lipidic debris leading to "ghost bodies" and calcifying globules. Light microscopical evaluation of 8 sural nerve specimens revealed a neuropathy in only 2 patients that was predominantly axonal in type and of slight to moderate severity with a secondary demyelinating component in 1 patient. These findings add to the large spectrum of muscle and nerve fiber changes in MD underlining the phenotypic multiplicity of a well defined genetic defect.     

多灶运动神经病病人的临床和神经电生理研究

目的：分析多灶运动神经病（multifocal motor neuropathy,MMN）的临床及神经电生理特点。方法：对13例MMN患者进行神经传导和常规肌电图（EMG）检查,采用微移（inching）技术判定是否有运动神经传导阻滞（CB）。结果：全部患者均隐袭起病,进展缓慢,临床上以单肢无力为首发症状,随病情发展,受累部位增加。常规神经传导检查可见所有明显萎缩肌肉的复合肌动作电位（CMAP）波幅下降;13例患者神经受累区域以下所支配肌肉EMG检查可见不同程度的神经原性损害。采用微移技术共测定出CB25处和拟诊CB6处。在3条临床及EMG测定均正常的神经发现5处CB,其余26处CB或拟诊CB均发生于轻度至中度无力的肌肉所对应的20条神经。结论：MMN是一种以远端神经受累为主的不对称性周围神经病,神经电生理检查对诊断和鉴别诊断MMN起重要作用,CB是MMN的主要神经电生理表现。     

甲状腺机能亢进伴发重症肌无力患者电生理研究

目的：探讨甲状腺机能亢进（甲亢）伴发重症肌无力（MG）患者的电生理检测特点，和与慢性甲状腺机能亢进性肌病（CTM）的关系。方法：对7例甲亢伴发MG患者进行神经传导速度（NCV）、重复电刺激（RNS）、针极肌电图（EMG）和单纤维肌电图（SFEMG）检测。结果：7例NCV均正常，RNS5例异常。EMG2例发现有肌病的表现，SFEMG均出现jitter增宽。结论：甲亢病人可伴发MG，还可能同时伴发CTM，进行RNS、EMG、SFEMG检测是有必要的。     

Genetic epidemiology of hereditary motor sensory neuropathies (type I)

Patients affected with hereditary motor sensory neuropathy (HMNS) type I were traced through hospital records. Each case was re-examined, a family history was drawn, and EMG examination was performed in those members of the family who could have inherited the trait. In the prevalence year 1987, in a population of 1,067,130 inhabitants of 2 contiguous provinces of northeast Italy, 100 living cases were recorded in 30 families, giving a minimal prevalence rate estimate of 9.37/100,000. HMSN I is inherited as an autosomal dominant trait, when clinical evaluation includes EMG. No difference may be established clinically between the 2 subtypes (Ia, linked to chromosome 1 and Ib, linked to chromosome 17). Sporadic cases are very rare and the mutation rate, including both the subtypes, is estimated between 3 and 6 X 10(-6).     

A study of morphometric and histopathological features of muscle biopsies from patients of myopathy

The aim of this study is to analyse the morphological pattern of different types of myopathies including morphometric data. The cases were diagnosed as myopathy on the basis of clinical details, EMG findings, serum CK values. Muscle biopsies were performed and hematoxylin & eosin stain and Masson's trichrome stain were done. Muscle fiber diameters were measured using an eye piece micrometer of 100 fibers in each biopsy, these values were plotted and histograms were constructed. From this, mean fiber diameter (MFD), standard Deviation (SD), atrophy factor (AF), hypertrophy factor (HF) and variability coefficient (VC) were calculated. Degree of inflammation was scored semiquantitatively and presence of degenerating fibers, regenerating fibers, perifascicular atrophy, perivascular lymphocytic infiltration and vasculitis were noted. Out of 25 patients, 9 patients of inflammatory myopathy were adults, of the 16 patients of dystrophy 9 patients were adults. Along with weakness of limbs, skin rash was seen in 2 patients of dermatomyositis. Degree of inflammation was more in the patients of inflammatory myopathy than in the patients of dystrophy. Necrotic and regenerating fibers were seen in both groups. Perifascicular atrophy was seen in 1 case of dermatomyositis. Atrophy factor was higher in cases of dystrophy and so was hypertrophy factor. Variability coefficient >250 was found on 90% of dystrophy cases and it was <250 in the cases of inflammatory myopathy. Morphometry provides valuable data, which helps in distinguishing dystrophy from cases of myopathy with inflammation.     

Facioscapulohumeral muscular dystrophy. A quantitative electromyographic study

BACKGROUND: Quantitative electromyography (EMG) using different needle techniques has not been performed or reported on a relatively large group of patients with facioscapulohumeral muscular dystrophy (FSHD). Purpose: To establish statistically: (1) correlations between clinical features of patients (age, disease duration and degree of weakness) and quantitative needle EMG/SFEMG,; (2) correlations between different EMG parameters in the patient group, and (3) quantitative EMG differences comparing patients with a healthy control group. METHODS: Nerve conduction studies, and needle EMG (motorunit analysis, MacroEMG, SFEMG) were performed on Mm. triceps brachii and Mm. tibialis anterior according to standard techniques on 20 patients with FSHD. RESULTS: Nerve conduction studies were normal. In Mm. triceps brachii and, to a lesser extent, Mm. tibialis anterior motorunit analysis and MacroEMG showed myopathic changes, that correlated with patient clinical parameters. In Mm. triceps brachii (but not in Mm. tibialis anterior) EMG results were statistically different in patients compared to control group data. The most sensitive indicators of a myopathy were MUP duration (motorunit analysis) and MUP area (MacroEMG). In the Mm. triceps brachii SFEMG revealed correlations between worsening pooled MCD data and patient clinical parameters. Pooled MCD results did not correlate with other MUP parameters. SFEMG showed abnormal jitter only in 2 patients with the longest disease duration. CONCLUSION: Quantitative EMG results are compatible with a mild, slowly progressive myopathy. The most sensitive indicators of early muscle disease were MUP duration (motorunit analysis) and MUP area (MacroEMG) that would not be detected on "routine" EMG SFEMG showed subtle, progressive worsening of neuromuscular junction physiology. However, quantitative EMG and SFEMG showed that muscle fiber degeneration and loss followed a course independent of muscle fiber regeneration and reinnervation.     

中毒性周围神经病的肌电图及神经电图分析

目的:探讨肌电图,神经电图对中毒性周围神经病的诊断价值及预后评估。方法:对25例中毒性周围神经病患者进行肌电图、神经电图检查。结果:68块被检肌肉30块(44.1％)出现自发电位;106条运动神经传导速度(MCV)测定,53条(50％)减慢,60条(56.6％)动作电位波幅降低;71条感觉神经传导速度(SCV)测定,34条(47.8％)减慢,56条(78.8％)动作电位波幅降低。结论:中毒性周围神经病的肌电、神经电图改变均为周围神经损害,表现为髓鞘和轴索同时受损,并以轴索受损为主。为临床诊断、鉴别诊断以及了解病损程度均有重要价值。     

Mutations and sequence variation in the human myosin heavy chain IIa gene (MYH2)

We recently described a new autosomal dominant myopathy associated with a missense mutation in the myosin heavy chain (MyHC) IIa gene (MYH2). In this study, we performed mutation analysis of MYH2 in eight Swedish patients with familial myopathy of unknown cause. In two of the eight index cases, we identified novel heterozygous missense mutations in MYH2, one in each case: V970I and L1061V. The mutations were located in subfragment 2 of the MyHC and they changed highly conserved residues. Most family members carrying the mutations had signs and symptoms consisting mainly of mild muscle weakness and myalgia. In addition, we analyzed the extent and distribution of nucleotide variation in MYH2 in 50 blood donors, who served as controls, by the complete sequencing of all 38 exons comprising the coding region. We identified only six polymorphic sites, five of which were synonymous polymorphisms. One variant, which occurred at an allele frequency of 0.01, was identical to the L1061V that was also found in one of the families with myopathy. The results of the analysis of normal variation indicate that there is strong selective pressure against mutations in MYH2. On the basis of these results, we suggest that MyHC genes should be regarded as candidate genes in cases of hereditary myopathies of unknown etiology.