Single fiber electromyography and measuring jitter with concentric needle electrodes.

This monograph contains descriptions of the single fiber electromyography (SFEMG) method and of the more recently implemented method of recording jitter with concentric needle electrodes (CNEs). SFEMG records action potentials from single muscle fibers (SFAPs), which permits measuring fiber density (FD), a sensitive measure of reinnervation, and jitter, a sensitive measure of abnormal neuromuscular transmission (NMT). With voluntary activation, jitter is measured between two SFAPs with acceptable amplitude and rise time. With activation by axon stimulation, jitter is measured between the stimulus and individual SFAPs. Pitfalls due to unstable triggers and inconstant firing rates during voluntary activation and subliminal stimulation during axon stimulation should be identified and avoided. In CNE recordings, spikes with shoulders or rising phases that are not parallel are produced by summation of SFAPS; these should be excluded and reference values for CNE jitter should be used. CNE and SFEMG have similar and very high sensitivity in detecting increased jitter, as in myasthenia gravis and other myasthenic conditions. However, jitter is also seen in ongoing reinnervation and some myopathic conditions. With SFEMG, these can be identified by increased FD; however, FD cannot be measured with CNE, and conventional electromyography should be performed in muscles with increased jitter to detect neurogenic or myogenic abnormalities. Jitter is abnormal after injections of botulinum toxin, even in muscles remote from the injection site, and can persist for 6 mo or more. This can complicate the detection or exclusion of abnormal NMT.

Single fiber EMG and measuring jitter with concentric needle electrodes.

This monograph contains descriptions of the single-fiber electromyography (SFEMG) method and of the more recently implemented method of recording jitter with concentric needle electrodes (CNE). SFEMG records action potentials from single muscle fibers (SFAPs), which permits measuring fiber density (FD), a sensitive measure of reinnervation, and jitter, a sensitive measure of abnormal neuromuscular transmission (NMT). With voluntary activation, jitter is measured between two SFAPs with acceptable amplitude and rise time. With activation by axon stimulation, jitter is measured between the stimulus and individual SFAPs. Pitfalls due to unstable triggers and inconstant firing rates during voluntary activation and subliminal stimulation during axon stimulation should be identified and avoided. In CNE recordings, spikes with shoulders or rising phases that are not parallel are produced by summation of SFAPS; these should be excluded and reference values for CNE jitter should be used. CNE and SFEMG have similar and very high sensitivity in detecting increased jitter, as in myasthenia gravis and other myasthenic conditions. However, jitter is also seen in ongoing reinnervation and some myopathic conditions. With SFEMG, these can be identified by increased FD; however, FD cannot be measured with CNE, and conventional EMG should be performed in muscles with increased jitter to detect neurogenic or myogenic abnormalities. Jitter is abnormal after injections of botulinum toxin, even in muscles remote from the injection site, and can persist for 6 mo or more. This can complicate the detection or exclusion of abnormal NMT.

Congenital myasthenic syndrome: Correlation between clinical features and molecular diagnosis.

OBJECTIVES: To present phenotype features of a large cohort of congenital myasthenic syndromes (CMS) and correlate them with their molecular diagnosis. METHODS: Suspected CMS patients were divided into three groups: group A (limb, bulbar or axial weakness, with or without ocular impairment, and all the following: clinical fatigability, electrophysiology compatible with neuromuscular junction involvement and anticholinesterase agents response), group B (limb, bulbar or axial weakness, with or without ocular impairment, and at least one of additional characteristics noted in group A) and group C (pure ocular syndrome). Individual clinical findings and the clinical groups were compared between the group with a confirmed molecular diagnosis of CMS and the group without molecular diagnosis or with a non-CMS molecular diagnosis. RESULTS: Seventy-nine patients (68 families) were included in the cohort: 48 in group A, 23 in group B and 8 in group C. Fifty-one were considered confirmed CMS (30 CHRNE, 5 RAPSN, 4 COL13A1, 3 DOK7, 3 COLQ, 2 GFPT1, 1 CHAT, 1 SCN4A, 1 GMPPB, 1 CHRNA1), 7 probable CMS, 5 non-CMS and 16 unsolved. The chance of a confirmed molecular diagnosis of CMS was significantly higher for group A and lower for group C. Some individual clinical features, alterations on biopsy and electrophysiology enhanced specificity for CMS. Muscle imaging showed at least mild alterations in the majority of confirmed cases, with preferential involvement of soleus, especially in CHRNE CMS. CONCLUSIONS: Stricter clinical criteria increase the chance of confirming a CMS diagnosis, but may lose sensitivity, especially for some specific genes.

Peripheral nerve injuries: A retrospective survey of 1124 cases.

BACKGROUND: Peripheral nerve injuries (PNIs) remain an important health problem often leading to severe motor disabilities predominantly in the younger population. OBJECTIVE: To analyze our experience of clinical and electrodiagnostic evaluation (EDX) of PNIs over a 26-year period. MATERIALS AND METHODS: Between 1989 and 2014, 1124 consecutive patients with 1418 PNIs were referred for clinical as well as EDX evaluation. These PNIs involved upper and lower limbs as well as the facial nerves. Patients with iatrogenic lesions and spinal cord/spinal root lesions were excluded from this analysis. Brachial plexus (BP) injuries with associated or not with root avulsions were considered as one particular nerve and was include in the study as BP. The etiological categories of the sustained trauma included vehicular accidents, penetrating injuries, falls, gunshot wounds, car accidents involving pedestrians, sports injuries, and miscellaneous injuries. RESULTS: The mean age of our patients was 34.2 years and most were males (76.7%). Majority (80.9%) of the PNIs were isolated injuries. Combined lesions most commonly involved the ulnar and median nerves. Upper-limb PNIs accounted for 72.6% of our patients. The ulnar nerve was injured most often, either singly or in combination. Vehicular accidents were the most common causes of injury (46.4%), affecting the brachial BP or the radial, fibular, or sciatic nerves. Penetrating trauma (23.9%) commonly affected the ulnar and the median nerves. Falls and gunshot wounds frequently affected the ulnar, radial, and median nerves. Sports injuries, mostly soccer related, affected predominantly the fibular nerves. BP injuries were considerably more common in accidents involving motorcycles than those involving cars (46.1% vs. 17.1%), and root avulsions was more frequently associated in these cases. CONCLUSIONS: Most PNIs were caused by vehicular accidents and penetrating trauma, and affected young men. Overall, ulnar nerve, primary BP, and median nerve PNIs were the most prevalent lesions.

Concentric needle jitter on voluntary activated frontalis in 20 healthy subjects.

INTRODUCTION: Normative data for jitter parameters using a disposable concentric needle have been described in a few studies. METHODS: Jitter, expressed as the mean consecutive difference (MCD), was measured in the frontalis muscle in 20 subjects by voluntary contraction. RESULTS: Mean MCD for individual studies (20, gaussian), all potentials (400, non-gaussian), and 18th highest value (20, gaussian) were 19.9 ± 2.9 µs, 19.9 ± 6.6 µs, and 26.9 ± 4.4 µs, respectively. CONCLUSION: The suggested upper normal limit for mean MCD is 26 µs and for outliers is 36 µs.

Concentric needle jitter in stimulated frontalis in 20 healthy subjects.

Normative data for jitter parameters using a disposable concentric needle have been presented in a few studies. Jitter, expressed as the mean consecutive difference (MCD), was measured in the frontalis muscle in 20 subjects by percutaneous bar stimulation of the temporal nerve branch. The mean MCD for individual studies (20) and for all potentials (600) were 16.05 ± 2.73 µs and 16.05 ± 5.96 µs, respectively. The suggested limit for mean MCD is 22 µs and for outliers is 28 µs.

Quantitation of muscle pathology abnormalities in 18 patients with mitochondrial disorders / Quantificação das anormalidades patológicas musculares em 18 pacientes com desordens mitocondriais

ABSTRACT INTRODUCTION: Mitochondrial disorders can lead to the accumulation of mitochondria in muscle fibers, as indicated by ragged red (RRF) or ragged blue fibers when stained with modified Gomori trichrome or succinate dehydrogenase (SDH+), respectively, and, absence of activity of cytochrome c oxidase, COX negative fibers (COX-). The combined COX-SDH stain (COMBO+) can reveal even more COX-deficient fibers. OBJECTIVE: To quantify RRFs, SDH+, COX-, and COMBO+ fibers in muscle biopsies with mitochondrial findings. MATERIAL AND METHODS: We retrospectively selected 18 muscle biopsies with mitochondrial abnormalities based on the Walker criteria (percentage of RRFs/COX- fibers, and clinical picture), and/or the Sleigh criteria (percentage of RRFs, SDH+, and COX- fibers). RESULTS: Females represented 83.3%, with a mean age of 38.6 years (5 months-70 years). Patients were diagnosed with chronic progressive external ophthalmoplegia (CPEO, 66.7%), proximal myopathy (22.2%), idiopathic hyperCKemia (11.1%), Kearns-Sayre syndrome (5.6%), mitochondrial encephalomyopathy with ragged red fibers and stroke-like episodes (5.6%), and a dystrophic pattern (5.6%). Some cases of CPEO were combined with proximal myopathy. The quantitative pathologic findings were: RRFs, 3.95% ± 3.17%; SDH+, 7.55% ± 6.1%; COX-, 10.9% ± 7.2%; COMBO+, 14.22% ± 12.79%. We found a slight variation in the diameter of muscle fibers, no necrosis or proliferative connective tissue, few fibers with internal nuclei, and some cases with fiber type grouping. CONCLUSION: Pathologic events, grouped in ascending order of frequency, were RRFs, SDH+ fibers, COX- fibers, and COMBO+ fibers. These data emphasize the importance of the COMBO technique in revealing occult COX deficiency in muscle fibers.

RESUMO INTRODUÇÃO: Desordens mitocondriais são usualmente caracterizadas por: 1. acúmulo de mitocôndria nas fibras musculares que aparecem como fibras vermelhas rasgadas (FVR) ou azuis rasgadas quando coradas, respectivamente, pelo tricrômio modificado de Gomori ou pelo succinato desidrogenase (SDH+); 2. ausência de atividade da citocromo c oxidase (COX), originando fibras COX negativa (COX-). A combinação de colorações COX e SDH pode revelar ainda mais fibras COX deficiente (COMBO+). Objetivos: Quantificar FVR, SDH+, COX- e COMBO+ em biópsias musculares com anormalidades mitocondriais. MATERIAL E MÉTODOS: Foram analisadas retrospectivamente 18 biópsias com anormalidades mitocondriais com base no critério de Walker (percentagem de FVR/ COX- e quadro clínico) e/ou critério de Sleigh (percentagem de FVR, SDH+ e COX-). RESULTADOS: Sexo feminino representou 83, 3% e média de idade 38, 6 anos (5 meses a 70 anos). Oftalmoplegia externa progressiva crônica (OEPC) representou 66, 7%; miopatia proximal, 22, 2%; hiperCKemia idiopática, 11, 1%; síndrome de Kearns-Sayre, 5, 6%; encefalopatia mitocondrial com FVR e episódios semelhantes a acidente vascular cerebral, 5, 6%; e padrão distrófico, 5, 6%. Alguns casos de OEPC estavam associados à miopatia proximal. Achados patológicos quantitativos: FVR, 3, 95% ± 3, 17%; SDH+, 7, 55% ± 6, 1%; COX-, 10, 9% ± 7, 2%; COMBO+, 14, 22% ± 12, 79%. Encontramos leve variação de calibre das fibras musculares sem necrose ou proliferação de tecido conjuntivo, poucas fibras com núcleos internos e alguns casos com agrupamento de fibras. CONCLUSÃO: As anormalidades patológicas nas fibras musculares em ordem ascendente de frequência foram: FVR, SDH+, COX- e COMBO+. Nossos achados enfatizam a importância da técnica COMBO (COX + SDH) para aumento na frequência de fibras musculares COX deficiente ocultas.

NINJURIN1 single nucleotide polymorphism and nerve damage in leprosy.

UNLABELLED: Leprosy, a chronic infectious disease caused by Mycobacterium leprae, can damage the peripheral nervous system and represents one of the leading causes of nontraumatic neuropathy in some developing countries. The NINJURIN1 is a cell adhesion molecule that provides suitable substrates for repair of Schwann cells after peripheral nerve injury. The single nucleotide polymorphism NINJ1, is the result of a transversion of an adenine to a nucleotide polymorphic cytokine (A→C), responsible for an amino acid exchange of asparagine to alanine at position 110 of the protein (asp110ala). OBJECTIVES: The aim of this study was to investigate the importance of the polymorphism in the NINJ1 gene for neural impairment during leprosy course. METHODS: A single nucleotide polymorphism (asp110ala) was searched in 218 leprosy patients and 244 non-leprosy subjects using a polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: No statistical differences were observed in the frequency of the asp110ala SNP between leprosy patients versus non-leprosy and multibacillary versus paucibacillary clinical forms. The C allele (ala110) is increased among patients exhibiting nerve impairment (p=0.0379). Also, leprosy patients with the CC genotype (ala/ala) had a higher risk (OR=4.21) of developing nerve disability when compared those carrying the AA genotype (asp/asp) (OR=0.69). CONCLUSION: Our results show an association between the studied C allele (ala110) and damage nerve in leprosy patients. SIGNIFICANCE: Ninjurin analysis showed that asp110ala could be a valuable prognostic marker, since C allele (ala110) have increased susceptibility to nerve damage.

Evaluation of age, body mass index, and wrist index as risk factors for carpal tunnel syndrome severity.

To determine the role of personal variables as risk factors for carpal tunnel syndrome (CTS) and their relationship to severity of nerve conduction abnormality, we studied 210 consecutive symptomatic CTS patients and 320 controls subjects without CTS symptomatology or known systemic disorders. The CTS group was classified according to the severity of nerve conduction changes. The risk factors for CTS and its severity were assessed by means of univariate and multivariate analysis. Presence of CTS was significantly related to increase of body mass index (BMI) and wrist index. More severe nerve conduction abnormalities were associated with greater age and wrist index but not with higher BMI.

Biópsia muscular com estudo histoquímico: experiência inicial da Faculdade de Medicina de São José do Rio Preto / Muscle histochemistry: a study of the first 55 biopsies in São José do Rio Preto

São apresentados os primeiros 55 casos de biópsia muscular com estudo histoquímico da Faculdade de Medicina de São José do Rio Preto. A histoquímica muscular permite: 1. Revelar a natureza não uniforme dotecido muscular demonstrando as propriedades bioquímicas de diferentes tipos de fibra e sua participação seletiva em determinadas doenças; 2. Detectar ausência de enzimas específicas; 3. Detectar excesso ou acúmulo de substratos específicos; 4. Detectar anormalidades estruturais musculares que não aparecem nas reações histológicas rotineiras. A média de idade foi de 28,6 anos, variando de 25 dias a 76 anos, 56,4% eram do sexo masculino e 43,6% feminino. Foram rotineiramente utilizadas as seguintes técnicas: Hematoxilina &Eosina, Tricrômio de Gomori modificado, Citocromo-C-Oxidase, Dinucleotídeo Adenina Nicotinamida Desidrogenase reduzida pelo tetrazólio, Succinato-Desidrogenase, Fosfatase Alcalina, Fosfatase Ácida, Adenosina Trifosfato miofibrilar pré-incubadas a pH 9,4, 4,6 e 4,3, Ácido Periódico de Schiff e Oil-Red-O. Anormalidades foram encontradas em 72,8% das biópsias, sendo de padrão distrófico em 17 casos, inflamatório em 7 casos, mitocondrial em 6 casos, reinervação crônica em 4 casos, glicogenose em 2 casos e outros diagnósticos em 4 casos. Anormalidades mínimas ou inespecíficas foram encontradas em 5 casos (9%) e em10 casos (18,2%) foram normais. Nossos achados foram semelhantes aos de outros descritos na literatura nacional. A biópsia muscular como estudo histoquímico, ainda inexistente na região Noroeste do estado deSão Paulo, é uma das armas diagnósticas mais importantes para as doenças neuromusculares.

We present the muscle histochemistry from the first 55 biopsies at the State Medical School of São José doRio Preto, São Paulo, Brazil. Muscle histochemistry first, demonstrate the non-uniform nature of muscular tissue showing biochemical properties from different fiber types and their selective involvement in particular diseases; second, demonstrate the absence of specific enzymes; third, demonstrate abnormal storage of specific substrates, and fourth, demonstrate structural abnormalities that are not seen on ordinary histological stainings. The mean age was 28.6 years, ranging from 25 days to 76 years, 56.4% male and 43.6% female. Ourroutine techniques, done in all biopsies, included: Hematoxylin and Eosin, Gomori Trichrome, CytochromeOxidase, NADH dehydrogenase, Succinic Dehydrogenase, Alkaline Phosphatase, Acid Phosphatase, ATPase pH 9.4, 4.6 and 4.3, Periodic-acid Schiff and Oil-Red-O. Abnormalities were found in 72.8%, being dystrophicin 17 cases, inflammatory in 7 cases, mitochondrial in 6 cases, chronic reinnervation in 4 cases, glycogen storage disorder in 2 cases and other diagnostics in 4 cases. Minimal or unspecific abnormalities were found in 5 cases (9%) and were normal in 10 cases (18.2%). Our findings were similar to others described in Brazil. Muscle histochemistry is one of the most significant diagnostic tools for neuromuscular disorders and was not done before in this region of Brazil.

Potenciais evocados multimodais: estudos normativos em 51 indivíduos de uma populaçäo brasileira / Multimodality evoked potentials: normative studies 51 subjects of a brazilian population

Os autores relatam os resultados de estudos normativos de potenciais evocados visuais por padräo alterno-reverso, auditivos do tronco cerebral e sômato-sensitivos dos membros superiores e inferiores em amostra de 51 indivíduos normais de uma populaçäo brasileira. Foram estabelecidos valores normais para os principais componentes de cada modalidade de potenciais evocados, dando-se ênfase aqueles que têm maior utilidade clínica. Os resultados säo comparados com os dados registrados na literatura