Muscle fiber conduction abnormalities in early diabetic polyneuropathy.

OBJECTIVE: Diabetic polyneuropathy (PNP) has been proposed to be a primary disorder of sensory nerves. At an early stage motor nerve conduction velocity (MNCV) and muscle strength remain preserved due to compensatory mechanisms (axonal sprouting, reinnervation). We evaluated the use of invasive muscle fiber conduction velocity (MFCV) measurements as a method to detect muscle fiber denervation atrophy, as an early sign of motor axonal loss in diabetes mellitus (DM). METHODS: Twelve selected male patients (8 type 1, 4 type 2; mean age 35.8 years, SD 10.6), without any sign of micro- or macroangiopathy, were studied by systematic clinical and neurophysiological testing including MFCV estimation. RESULTS: Hand-held dynamometry was normal in all subjects. There were no signs of recent denervation by concentric needle EMG in any of the patients. Sensory nerve conduction velocity (SNCV) was abnormal in 6 subjects, MFCV in 6 subjects (5 had also low SNCV). The ratio of fastest/slowest muscle fibers in MFCV was correlated to SNCV of sural nerve (-.59, p < .05), but not to MNCV. CONCLUSIONS: Half of the clinically asymptomatic DM subjects showed sensory involvement together with MFCV abnormalities, despite normal needle EMG and force. SIGNIFICANCE: MFCV estimation offers a sensitive method in detecting early signs of motor axonal dysfunction in DM.     

Muscle fiber conduction velocity in situ (MFCV) in denervation, reinnervation and disuse atrophy

OBJECTIVES: Muscle fiber conduction velocity (MFCV) was performed in disuse atrophy, in denervated muscle and during reinnervation as a possible index of muscle atrophy, and to clarify the evolution of the fiber size. MATERIAL AND METHODS: MFCV was performed in 12 patients with complete denervation of biceps brachii muscle and during various stages of reinnervation. Twenty-one patients with disuse quadriceps atrophy were also tested. Invasive MFCV was performed according to the method reported elsewhere (2). RESULTS: MFCV decreased significantly in denervated muscles. Reduction of MFCV was found during the first weeks and was progressive. Peak frequency in histograms decreased and the normal Gaussian distribution was lost. MFCV increased progressively after reinnervation with coexistence of slow and significant increase of faster MFCV. MFCV decreased significantly also during the first weeks after immobilization and improved by rehabilitation therapy. CONCLUSION: MFCV is a reliable method to test the muscle fiber size after denervation and immobilization, and its evolution by reinnervation and therapy.     

Muscle Nogo-A expression is a prognostic marker in lower motor neuron syndromes

OBJECTIVE: A proportion of patients with pure lower motor neuron syndrome (LMNS) progress to amyotrophic lateral sclerosis (ALS). Early detection of this progression is impossible, which delays the patient's access to treatment. Muscle expression of Nogo-A is a new candidate marker of ALS. We tested whether detection of Nogo-A in a muscle biopsy from patients with LMNS predicts progression to ALS. METHODS: Thirty-three patients who had undergone a muscle biopsy during the diagnostic workup of spinal LMNS were observed for 12 months. Nogo-A expression was measured by Western blot in muscle biopsy samples and compared with the final diagnosis. RESULTS: Nogo-A expression was detected in 17 patients and was absent in 16 patients. The detection of Nogo-A in muscle biopsy samples from LMNS patients correctly identified patients who further progressed to ALS with 91% accuracy, 94% sensitivity, and 88% specificity. In patients who later developed typical ALS, Nogo-A may be detected as early as 3 months after the onset of symptoms. INTERPRETATION: Nogo-A test is able to identify ALS early in the course of the disease when diagnosis is difficult, requiring further progression. Use of the test in clinical practice may shorten the delay before introduction of neuroprotective drugs or inclusion in clinical trials.     

Diagnostic yield of muscle fibre conduction velocity in myopathies

We prospectively assessed diagnostic yield of muscle fiber conduction velocity (MFCV) studies in patients with signs and symptoms suggestive of a myopathy. Results were analysed with respect to the final diagnosis, and compared to the reference standard, which was qualitative electromyography (EMG), turns-amplitude analysis (TAA), and muscle biopsy. We included 125 patients, in whom a myopathy was diagnosed in 71, and a neuromuscular disorder was excluded in 54. Sensitivity of MFCV for the presence of a myopathy was 84%, and specificity 83%. Diagnostic yield of MFCV was superior to EMG, TAA, and muscle biopsy in patients with metabolic myopathies, non-dystrophic myopathies, and channelopathies. We concluded that measurement of MFCV is a quantitative EMG technique with a high diagnostic yield. In certain myopathies, MFCV may be more informative than conventional EMG examination.     

Role of electromyography in amyotrophic lateral sclerosis.

We reviewed the role of electrodiagnostic testing in amyotrophic lateral sclerosis (ALS) in a large ALS clinic. Over 31 months, 133 patients with a clinical diagnosis of ALS were tested. In most, nerve conduction studies were normal, and needle electrode examination showed active denervation in the upper and lower limbs or the limbs and bulbar muscles (Lambert's criteria). However, 50 of 133 patients did not fulfill Lambert's criteria at presentation because of abnormal nerve conduction studies (11 patients), abnormal F-wave latencies (6 patients), or insufficiently distributed fibrillation potentials (40 patients). This study reveals that a large proportion of patients with a clinical diagnosis of ALS fail to have classical findings on initial electrodiagnostic studies, and reveals several caveats of electrodiagnostic testing in these patients: (1) Conduction studies may be unreliable in motor nerves with markedly low compound muscle action potential (CMAP) amplitudes. (2) Sensory nerve action potential (SNAP) amplitudes may be abnormal in a small percentage of otherwise typical ALS patients. However, better controls for elderly subjects are needed. (3) Needle electrode examination may not show widespread active denervation early in the disease. (4) Some patients may have a mild polyneuropathy. (5) The classic diagnostic criteria may need to be modified to allow earlier acceptance of many ALS patients into therapeutic trials.     

The prevalence of rimmed vacuoles in biopsy‐proven dermatomyositis

The causal relationship between electrical injury and development of amyotrophic lateral sclerosis (ALS) remains controversial. We describe the case of a 25‐year‐old man who developed ALS after a severe electrical injury. Cerebral magnetic resonance imaging (MRI) demonstrated hyperintensities involving the corticospinal tract. Functional testing with transcranial magnetic stimulation established that the motor cortex was relatively inexcitable. In addition, there were features of denervation on electromyography and muscle biopsy that supported concomitant lower motor neuron findings and the diagnosis of ALS. Muscle Nerve, 2010     

Paraspinal and limb motor neuron involvement within homologous spinal segments in ALS.

OBJECTIVE: We studied the involvement of motor neuron groups innervating paraspinal muscles in amyotrophic lateral sclerosis (ALS) and evaluated the value of paraspinal muscle EMG in the diagnosis of the disease. METHODS: We used quantitative concentric needle EMG to study denervation and reinnervation in a paraspinal muscle and a limb muscle innervated by the C6 and L5 segments in 32 patients with ALS. As control subjects we studied 11 patients with peripheral neuropathy, and 46 non-neurogenic control subjects. RESULTS: We found similar abnormalities in motor-unit potentials (MUPs) in paraspinal and limb muscles in these two segments in ALS. Fasciculation potentials (FPs) were more frequent in limb muscles than in paraspinal muscles and fibrillations and sharp waves (fibs-sw) were most frequent in tibialis anterior. In peripheral neuropathy paraspinal muscles were normal but tibialis anterior showed very abnormal motor unit potentials. CONCLUSIONS: These results are consistent with generalised involvement of motor neurons in motor neuron pools in spinal segments in early stages of ALS progression. However, distally predominant fibrillations indicate susceptibility to ongoing denervation in reinnervated distal axons. Complex FPs of similar morphology to MUP analysis in the same early affected muscle suggests a proximal origin for these FPs at this phase. SIGNIFICANCE: Our observations emphasize the value of paraspinal muscle EMG in the electrophysiological diagnosis of ALS.     

Somatosensory evoked potentials in the differential diagnosis between compression and amyotrophic srinal cord literal sclerosis

Spinal cord compression (SCC) often presents a similar clinical picture to amyotrophic lateral sclerosis (ALS). An early differential diagnosis is important because SCC is a potentially treatable clinical disorder. We carried out a longitudinal study of 43 patients with an initial diagnosis of ALS, in order to ascertain the percentage of patients with SCC, and to evaluate the usefulness of somatosensory evoked potentials (SEPs) in early diagnosis. Thirty-three patients had a final diagnosis of ALS and 8 of SCC. SEPs central conduction was abnormal in 3 ALS and 7 SCC patients, respectively (Fisher exact test, p < 0.05). We concluded that SEPs investigation is useful in the differential diagnosis between ALS and SCC patients with pure motor signs.     

Awaji ALS criteria increase the diagnostic sensitivity in patients with bulbar onset

ObjectiveTo assess whether Awaji criteria improve the sensitivity of diagnosis for amyotrophic lateral sclerosis (ALS). In Awaji ALS criteria, fasciculation potentials are regarded as evidence of acute denervation in the presence of chronic neurogenic changes on needle electromyography.MethodsWe reviewed clinical and neurophysiological data of 113 consecutive patients who were suspected as suffering ALS. The six muscles (trapezius, biceps, first dorsal interosseous, T10-paraspinalis, vastus lateralis, and tibialis anterior muscles) were examined by EMG, focusing on the presence of fasciculation potentials. The sensitivity of revised El Escorial (R-EEC) and Awaji criteria was compared.ResultsProbable or definite ALS was diagnosed in 61% of the patients by R-EEC and 71% by Awaji criteria. By applying Awaji criteria; (1) 17 of the 44 patients categorized as possible ALS by R-EEC reached to probable/definite ALS, 11 of whom had bulbar onset, (2) in 48 patients with bulbar onset, the proportion of probable/definite ALS increased from 59% to 82%, (3) in 62 patients with limb onset, the proportion of probable/definite ALS was 61% (63% by R-EEC).ConclusionsAwaji criteria improve the sensitivity of ALS diagnosis in patients with bulbar onset, but not in those with limb onset.SignificanceAccepting fasciculation potentials as evidence of acute denervation increases the diagnostic sensitivity of ALS, particularly in patients with bulbar onset, and contributes to early diagnosis.     

Muscle-fiber conduction velocity and electromyography as diagnostic tools in patients with suspected inflammatory myopathy: a prospective study

Combinations of different techniques can increase the diagnostic yield from neurophysiological examination of muscle. In 25 patients with suspected inflammatory myopathy, we prospectively performed needle electromyography (EMG) and measured muscle-fiber conduction velocity (MFCV) in a single muscle, using a technique with direct muscle-fiber stimulation and recording. Results of MFCV were compared with final diagnosis, EMG, and needle muscle biopsy. Diagnostic accuracy of combined MFCV and EMG studies was 72%, compared to 60% for EMG alone. This improvement was due to a gain in specificity. The MFCV did not prove useful in discriminating inflammatory myopathy from other myopathies. Furthermore, we found a correlation of 92% between variability of MFCV and myopathic changes in muscle biopsy. We conclude that the utility of electrodiagnostic examination can be increased if EMG examination is combined with MFCV studies.     

Magnetoencephalographic evidence of abnormal auditory processing in amyotrophic lateral sclerosis with bulbar signs.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is characterized by progressive motor neuron damage that gives rise to muscle denervation. Besides motor neuron damage, conscious auditory processing appears to be impaired in ALS, whereas it has remained ambiguous whether preceding automatic auditory processing is abnormal in ALS and specifically in ALS with bulbar signs. METHODS: Auditory evoked fields (AEFs) to monaurally presented frequent and infrequent tones with stimulus intervals of 500 and 2500 ms were recorded with magnetoencephalography (MEG) from 10 ALS patients having bulbar signs and from 10 age-matched healthy subjects. RESULTS: The amplitudes of the P50m and N100m responses, which index automatic auditory processing underlying stimulus detection, were significantly increased and P50m latency was shortened in ALS patients. MMNm, which reflects memory-based auditory comparison process, was increased in amplitude in the patient group, whereas the MMNm latency was similar in both groups. AEF latency and amplitude values failed to correlate with the severity of ALS as measured by ALS Functional Rating Scale (ALSFRS). CONCLUSIONS: The present results suggest that auditory processing underlying stimulus detection, and subsequent memory-based comparison processes are abnormal in ALS patients with severe bulbar signs. This might be due to cortical overactivity of excitatory neurotransmitter glutamate observed in ALS.     

Neuropathy and myopathy in primary Sjögren''s syndrome: neurophysiological, immunological and muscle biopsy results

Seventeen consecutive patients with primary Sjögren's syndrome (PSS) received neurophysiological examination, analysis of antibodies against peripheral nerve-myelin (PNM) and muscle biopsy, to show the prevalence and characteristics of peripheral neuropathy (PN) and myopathy; 3 PSS cases showed a clinical mild sensorimotor polyneuropathy, 1 of them had been treated with cytostatic drugs; 1 had mononeuropathia multiplex; and 1 clinical carpal tunnel syndrome. In these 5 patients neurophysiological investigation verified the clinical diagnosis of peripheral nerve involvement; 2 with PN had serum-antibodies against PNM; 1 of IgM-, and 1 of IgA-isotype. Muscle biopsies were taken from 15 PSS patients; 11 showed inflammatory myositis or inflammatory perivascular infiltrates and 3 showed signs of denervation. A combination of inflammation and morphological signs of myopathy, compatible with the biopsy diagnosis of polymyositis, was seen in 4, 1 of whom showed clinical signs of polymyositis. We conclude that the peripheral nervous and muscular systems are often involved in PSS, but commonly with relatively mild symptoms and laboratory findings. The common findings of inflammatory myopathy indicate an immune reaction in muscles in addition to other autoimmune manifestations of the disease.     

Cervical spondylotic amyotrophy presenting as dropped head syndrome

We report a case of acute-onset dropped head syndrome in a 65-year-old patient in whom the diagnosis of amyotrophic lateral sclerosis (ALS) was initially proposed based on electromyographic signs of neck and shoulder muscle denervation. There were no signs of pyramidal involvement and the clinical and electromyographic signs of motor denervation never evolved beyond the neck and shoulder girdle muscles after a 6-year follow-up period, which argued against ALS. Other causes of dropped head syndrome were carefully ruled out based on clinical findings, electrodiagnostic studies and blood investigations. The restriction of muscle denervation to a few cervical myotomes, the presence of C3–C4 spondylotic changes without associated root or spinal cord compression, and the absence of an alternative explanation to the patient's symptoms strongly supported the diagnosis of cervical spondylotic amyotrophy (CSA). CSA is thought to result from spinal cord microcirculatory disturbances and secondary anterior horn cell degeneration due to ischemia. Our case enlarges the clinical spectrum of focal cervical anterior horn disease, which classically results in more distal monomelic atrophy affecting one or both upper limbs.     

Transcranial magnetic stimulation compared with upper motor neuron signs in patients with amyotrophic lateral sclerosis.

If patients with amyotrophic lateral sclerosis (ALS) present without upper motor neuron signs (UMNS) they do not meet current ALS research criteria. To compare how sensitively degeneration of upper motor neurons is detected clinically and by transcranial magnetic stimulation, 35 patients with ALS were studied. Nineteen patients had definite UMNS, nine patients had probable UMNS, and seven patients had no UMNS. Cortex, cervical nerve roots, and lumbar plexus were stimulated with a magnetic stimulator. Compound muscle action potentials from abductor digiti minimi and from anterior tibial muscles were recorded with surface electrodes. Responses to transcranial magnetic stimulation were considered abnormal if central motor conduction time was above the 99% upper limits or if there was no response to cortical but to peripheral stimulation. In all patients with definite UMNS central motor conduction was abnormal. In patients with probable UMNS it was abnormal in 67%, and in patients without UMNS it was abnormal in 71%. Abnormality of central motor conduction was neither correlated with the duration nor with the severity of the disease. The high rate of abnormalities of central motor conduction found in patients with ALS but without definite UMNS suggests that, in these patients, the diagnosis of ALS can be made more reliably if transcranial magnetic stimulation studies are performed.     

Syndromes of abnormal muscular activity: overlap between continuous muscle fibre activity and the stiff man syndrome.

Four patients with muscular pain, fasciculations, contractures or cramps are presented. Evidence of peripheral nerve involvement was revealed by electromyography and nerve conduction studies. Muscle biopsy showed mild signs of denervation and reinnervation and, at electron microscopy, dilatations of terminal cisternae were found. All patients showed a remarkable improvement after therapy with diphenylhydantoin or carbamazepine. These clinical, neurophysiological and morphological data underline the role of peripheral nerve pathology in various syndromes of abnormal continuous muscular activity.     

Muscular hypertrophy after chronic radiculopathy

In four patients, calf muscular hypertrophy developed after the onset of sciatica. Hypertrophic muscles were weak and showed electromyographic signs of denervation. In all cases, calf muscle biopsy showed striking hypertrophy of type 1 and, especially, type 2 muscle fibers. This hypertrophy was associated with other signs indicating a neurogenic lesion. Muscle hypertrophy is a rare finding in neurogenic lesions. Stretch and exercise of muscle are probably the causative factors.     

Needle electromyography of the frontalis muscle in patients with amyotrophic lateral sclerosis

Introduction: We sought to determine which muscles to choose for better assessment of the craniobulbar region in establishing the diagnosis of amyotrophic lateral sclerosis (ALS). Methods: We studied the frontalis muscle in 83 controls and compared it with the tongue, sternocleidomastoid (SCM), and trapezius muscles in 105 definite or probable ALS patients (54 bulbar, 51 nonbulbar). Results: More patients achieved complete relaxation of the frontalis muscle than the tongue or SCM. Motor unit potentials were of longer duration and higher amplitude in ALS patients than in controls (P < 0.05). The frontalis had the same frequency of spontaneous potentials as the tongue, SCM, and trapezius muscles in bulbar ALS patients, but fewer than in the trapezius in nonbulbar patients. Conclusions: Examining the frontalis provides useful information in establishing the diagnosis of ALS by identifying clinically evident or subclinical abnormalities in the craniobulbar region. Muscle Nerve 54 : 1093–1096, 2016     

肢带综合征1例及文献复习

目的:探讨淋巴瘤肌肉侵犯的临床特点。方法:报道1例肌肉病理确诊为淋巴瘤合并肌肉侵犯患者,对其临床、肌肉MRI表现和肌肉活检病理结果结合复习文献予以分析,总结淋巴瘤肌肉侵犯的临床特点。结果:淋巴瘤肌肉侵犯发生率较低,主要表现为受累肌肉肿块、疼痛和无力。MRI中可表现为局部肿块或弥漫性肿大及异常信号。肌肉活检及免疫组化有助于与肌炎鉴别和淋巴瘤的分型。以肌肉侵犯为主要表现的淋巴瘤化疗以CHOP方案为主,预后较好。结论:淋巴瘤肌肉侵犯可引起包括肢带综合征在内的肌病表现,有肌肉肿块或无力症状以及相应MRI表现的病例应考虑淋巴瘤肌肉侵犯可能。     

Identification of Tau and SOD1 gene mutation in a small Chinese Han pedigree of adult amyotrophic lateral sclerosis

We report the clinical profile, and a brief investigation of SOD1 and Tau gene mutation from a small Chinese Han pedigree of adults with amyotrophic lateral sclerosis (ALS), which consisted of 32 familial members with 6 affected individuals spanning five generations, and presenting autosomal dominant genetic mode. The mean age of onset was 36.6 ± 15.9 years, and disease duration was 6 months to more than 5 years, the average survival was 16.1 ± 8.2 months. There were 5 patients with an early disease onset, rapid progressive course and short survival, and 1 patient with late onset, slow progressive course and long survival in the kindred. ALS patients began to suffer with weakness and muscle atrophy in one side of a lower extremity, which then spread to the upper extremity, the opposite side and bulbar muscles. All patients had spinal onset type. Muscle stretch reflexes were absent or weak in the upper limbs and accentuation in the lower limbs; pathological signs in the lower limbs were positive. Electromyography disclosed ongoing denervation muscle potentials in the four extremities. Brain and spinal MRI did not show any abnormal signal. A 5 exons mutation of SOD1 in all affected individuals was identified using SSCP. Polymorphisms of partial risk regions in 3′,5′ UTR, and in introns 9, 10, 11, 12 of the Tau gene in the affected and normal family members and in 70 healthy controls were examined by DNA sequencing. Routine exons mutation of SOD1 was not detected, but one single nucleotide polymorphism of A to G at 138278 at 3′ UTR of the Tau gene was shown to significantly over-express in fALS familial members.     

Corticomotor threshold is reduced in early sporadic amyotrophic lateral sclerosis

The pathogenesis of idiopathic amyotrophic lateral sclerosis (ALS) remains unknown, but accumulating evidence suggests a neu roexcitotoxic mechanism may have some credence. Glutamate-induced hyperexcitability of cortical or spinal motoneurons may be expected to manifest itself as a reduced threshold for activation of these structures. We have measured corticomotor threshold to the first dorsal interosseous (FDI) muscles of 48 patients with sporadic ALS using magnetic brain stimulation and have correlated the findings with physical signs of upper and/or lower motor neuron degeneration. We find that if FDI in patients with ALS shows no weakness, wasting, or signs of an upper motor neuron lesion, mean corticomotor threshold is significantly lower than in 102 healthy control FDI muscles (P = 0.02). In contrast, FDI muscles showing signs of lower motor neuron degeneration only or mixed upper and lower motor neuron signs are associated with a raised corticomotor threshold (P = 0.008, P < 0.001, respectively). We conclude that early in ALS, at a time when hand muscle function is normal, corticomotor threshold is reduced and suggest that this may be a manifestation of abnormal excitability of cortical or spinal motoneurons to neurotransmitters, whose action will ultimately lead to cell death. © 1997 John Wiley & Sons, Inc. Muscle Nerve 20: 1137–1141, 1997