Fasciculaciones y calambres: bases fisiológicas y enfrentamiento clínico de un fenómeno complejo / Fasciculations and cramps: physiological bases and clinical approach of a complex phenomenon

Fasciculations and cramps originate in the motor unit, a functional unit that includes the lower motor neuron and their innervated muscle fibres. Both are common complaints in outpatient practice. These symptoms can be secondary to neurological or medical pathology, presenting a broad differential diagnosis and a complex approach. Recent neurophysiological studies have increased the knowledge of their origin mainly in amyotrophic lateral sclerosis. The symptomatic management of fasciculations and cramps depends on their etiology and includes pharmacological and non-pharmacological treatments. This article aims to present an updated review of the most relevant aspects of physiopathology, clinical approach, and differential diagnosis of both phenomena.

Peripheral nerve hyperexcitability syndrome: A clinical, electrophysiological, and immunological study.

INTRODUCTION: Peripheral nerve hyperexcitability syndrome (PNHS) is characterized by muscle fasciculations and spasms. Nerve hyperexcitability and after-discharges can be observed in electrophysiological studies. Autoimmune mechanisms play a major role in the pathophysiology of primary PNHS. METHODS: We retrospectively conducted a case-control study recruiting patients with clinical and electrophysiological features of PNHS. Control patients were diagnosed with other neuronal or muscular diseases. Contactin-associated protein2 (CASPR2) and leucine-rich glioma-inactivated1 (LGI1) antibodies were examined. RESULTS: A total of 19 primary PNHS patients and 39 control patients were analyzed. The most common symptoms for the case group were fasciculations (11/19) and muscle spasms (13/19). Case group patients were likely to demonstrate electrodiagnostic findings of nerve hyperexcitability (17/19) and after-discharges in the tibial nerve (19/19). We found high prevalence of CASPR2 (9/19) and LGI1 (6/19) antibodies in the case group. DISCUSSION: Primary PNHS patients were likely to show after-discharges in the tibial nerve. The pathogenesis of PNHS is autoimmune CASPR2 and LGI1 antibodies are possible pathogenic antibodies for primary PNHS.

Denny-Brown and Pennybacker: 80 years after their pioneering article on electromyography, fibrillation and fasciculation / Denny-Brown e Pennybacker: 80 anos da publicação de seu artigo pioneiro sobre eletromiografia, fibrilação e fasciculação

ABSTRACT We present a historical review, highlighting the role of Professor Derek Denny-Brown and doctor Joseph Buford Pennybacker in the development of current electromyography (EMG), of the 80 years since the publication of his original report in 1938 on fasciculation and fibrillation potentials and the subsequent studies describing most of the electrical changes necessary to perform and interpret the EMG.

RESUMO Os autores apresentam uma revisão histórica destacando o papel do Professor Derek Denny-Brown e do doutor Joseph Buford Pennybacker no desenvolvimento da eletromiografia atual, ao longo dos oitenta anos de seu artigo original em 1938, sobre potenciais de fasciculação e fibrilação, e os estudos subsequentes que descreveram a maioria das mudanças elétricas necessárias para realizar e interpretar EMG.

Perioral and tongue fasciculations in Kennedy's disease.

We report the case of a 54-year-old right-handed man who presented with a 2-year history of progressive upper-limb weakness with mild dysarthria and prominent involuntary perioral abnormal movements that were characterized as fasciculations. Electromyography disclosed motor neuron disease. The diagnosis of Kennedy's disease was established by polymerase chain reaction. Perioral abnormal movements and fasciculations may represent important clinical clues to the diagnosis of Kennedy's disease, particularly when associated with proximal muscle atrophy and gynecomastia. In suspected cases, genetic testing for elevated CAG repeats in the androgen receptor Xq12 gene is warranted.

Small fiber abnormalities in skin biopsies of patients with benign fasciculations.

OBJECTIVE: To determine whether patients with benign fasciculations have evidence for axonal loss in skin biopsies. METHODS: Epidermal sensory and sweat gland nerve fiber densities were quantified in skin biopsies of 11 patients with benign fasciculations and no other known cause for neuropathy. RESULTS: Nine of the 11 patients (82%) had significantly reduced epidermal or sweat gland nerve fiber densities at the calf or thigh, in comparison with control values. CONCLUSIONS: The presence of reduced epidermal and sweat gland nerve fiber density indicates the presence of axonal loss in patients with benign fasciculations.

Persistent idiopathic unilateral hypoglossal [corrected] nerve palsy: a case report.

Paralysis of the hypoglossal nerve, the twelfth (XII) cranial nerve, leads to atrophy, deviation of the tongue to the affected side, and varying degrees of fasciculation. The injury to the nerve can occur from its origin to the tongue itself. The causes of hypoglossal nerve palsy are well documented, but idiopathic, isolated nerve palsy that does not recover, is rare. To our knowledge we describe the first case that failed to resolve, and discuss the importance of meticulous investigation to make a diagnosis and rule out sinister disease.

Characteristics of fasciculations in amyotrophic lateral sclerosis and the benign fasciculation syndrome.

The aim of this study was to determine first, if benign fasciculations and those in amyotrophic lateral sclerosis can de distinguished on the basis of their waveforms or firing characteristics, and second to determine how fasciculation parameters evolved with progression of amyotrophic lateral sclerosis. Fasciculation potentials recorded from 63 muscles of 28 patients with definite amyotrophic lateral sclerosis were compared with those from 21 muscles of 11 patients with the benign fasciculation syndrome. In each muscle, at a single site, up to 15 identifiable fasciculation potentials could be recognized. Thus the characteristics of 430 fasciculations from patients with amyotrophic lateral sclerosis and 191 benign fasciculations were analysed. Fasciculation potential amplitude, area, turns, duration, firing interval, indices of waveform variability, evidence of axonal conduction block, evidence of axonal conduction variability and propensity to produce double fasciculations were measured. The waveforms of fasciculations in amyotrophic lateral sclerosis were on average of shorter duration and had a greater number of turns than benign fasciculations, but, although irregular in both conditions, the firing rate in amyotrophic lateral sclerosis was significantly higher. In both conditions, there was evidence of multifocal distal generation of fasciculations, axonal conduction block in the motor unit arborization and of variable axonal conduction. When severe weakness and marked chronic neurogenic change were present on electromyography, the firing rate of fasciculations in amyotrophic lateral sclerosis was higher but fasciculation potential amplitude, area and indices of waveform variability were little changed. Double fasciculations in which the waveforms of the two potentials were the same occurred in both conditions. The intervals were in two bands: an early band with 4-10 ms intervals showed identical waveforms of the two potentials, indicating the region of generation was the same. A second band of double fasciculation occurred in the tibialis anterior at an interval of 30-50 ms. Here, the first fasciculation waveform was variable in shape but the second fasciculation was the same on each occasion, suggesting reactivation of the fasciculation via the F-wave route. Double fasciculations in which the second discharge was different from the first had flat time-interval histograms, indicating no interaction between different fasciculations. In conclusion, benign and malignant fasciculations are not distinguishable on the basis of waveform; highly complex fasciculation potentials can be seen in both conditions. Fasciculation firing rate and the frequency of double fasciculations increases in amyotrophic lateral sclerosis when there is a marked lower motor neuron abnormality.

ANCA-related vasculitic neuropathy mimicking motor neuron disease.

Several conditions have been reported to mimic motor neuron disease (MND) and misdiagnosis remains a common clinical problem. Peripheral neuropathy is a classic feature of many vasculitic syndromes and in some patients it may be the only manifestation of vasculitis. We report a case of ANCA-related vasculitic neuropathy where the clinical presentation was suggestive of MND. A 42-year-old woman was admitted to our centre to confirm a diagnosis of MND made elsewhere. Clinical examination revealed postural tremor at the right hand, mild tongue atrophy with diffuse fasciculations and brisk tendon reflexes without other muscular weakness or atrophies. Electromyography demonstrated denervation in tongue and in the first dorsal interosseous of right hand ; motor evoked potentials disclosed normal central motor conduction time. Laboratory studies revealed only a mild increase of p-ANCA. A muscle biopsy showed a small inflammatory infiltrate around a vessel. The patient started high dosage of oral steroids. After one year of follow-up the patient suspended oral steroids, postural tremor of the right hand disappeared and tongue fasciculations were reduced. Vasculitis may mimic a MND, particularly in the absence of sensory involvement. Caution should be exercised in the clinical diagnosis of MND. Muscle biopsy is indicated in patient with atypical MND especially in those with an exclusive involvement of lower motor neuron.

Benign fasciculations responsive to gabapentin

Fasciculations are symptoms present in a broad spectrum of conditions, ranging from normal manifestations to motor neuron diseases. They also represent the main picture of benign fasciculation syndrome. We report a case of such syndrome: a 48-years-old woman complaining about fasciculations for three decades who remained with the symptoms even after the compensation of a disclosed hyperthyroidism. The introduction of gabapentin rendered control of her fasciculations. The available data in the literature about the therapeutic approaches for fasciculations are revised, as long as the rare reports of evolution from patients with "benign" fasciculations to cases of amyotrophic lateral sclerosis, underlining the importance of following the patients with fasciculations.

Fasciculações são sintomas presentes em um amplo espectro de condições, desde manifestações normais até doenças do neurônio motor. Elas representam também o principal aspecto da síndrome de fasciculações benignas. Relatamos um caso desta síndrome: uma paciente de 48 anos com queixas de fasciculações por três décadas que, mesmo após a compensação de um quadro de hipertireoidismo, permaneceu com os sintomas. A introdução de gabapentina levou a controle das fasciculações. Os dados disponíveis na literatura sobre as abordagens terapêuticas para fasciculações são revisados, assim como os raros relatos de evolução de pacientes com fasciculações "benignas" para casos de esclerose lateral amiotrófica, salientando a importância do seguimento dos pacientes com fasciculações.

Disfunción urinaria en el síndrome de Isaacs / Urinary dysfunctiion of acquired neuromyotonia (Isaacs'Syndrome)

La neuromiotonía es una afección que se presenta con endurecimiento muscular difuso, espasmos y/o acalmbres, usualmente asociados a hiperhidrosis, que pueden observarse en forma idiopática o secundaria. En 1961, Isaacs describió el síndrome en forma completa demostrando su origen en los nervios periféricos. Puede corresponder a patología hereditaria o adquirida, asociándopse a cuadros pareneoplásicos o autoinmunes, con o sin neuropatía periférica. Existe una sola coimunicación en la literatura de Síndrome de Isaacs con disfunción urinaria. Nosotros presentamos la primera descripción urodinámica realizada a una paciente con dicha entidad comprobando la presencia de una hiperreflexia rectal y del detrusor, hallazgos generalmente asociados a lesiones del SNC

Diagnosis of amyotrophic lateral sclerosis.

This review of the differential diagnosis of amyotrophic lateral sclerosis focuses on two themes. The first is practical, how to establish the diagnosis based primarily on clinical findings buttressed by electrodiagnosis. The main considerations are multifocal motor neuropathy and cervical spondylotic myelopathy. The second theme is the relationship of motor neuron disease to other conditions, including benign fasciculation (Denny-Brown, Foley syndrome), paraneoplastic syndromes, lymphoproliferative disease, radiation damage, monomelic amyotrophy (Hirayama syndrome), as well as an association with parkinsonism, dementia and multisystem disorders of the central nervous system.

Differential diagnosis of limb girdle syndromes.

The term limb girdle syndrome includes a variety of neuromuscular disorders like the scapulohumeral and pelvifemoral types of muscular dystrophy, quadriceps myopathy and Wohlfart-Kugelberg-Welander syndrome. There may be considerable difficulty in distinguishing between different types of limb girdle syndrome, even with the aid of electromyographic and muscle biopsy examinations. The aim of this investigation was to reestablish the clues for distinguishing between different types of limb girdle syndrome. Fifty-four patients with limb girdle syndromes took part in this investigation. They were subdivided into two groups according to EMG and muscle biopsy data. The first group consisted of 39 patients with limb-girdle type of muscular dystrophy and the second group consisted of 15 patients with juvenile type of spinal muscular atrophy. Our results revealed that neurological examination was not enough to distinguish the different types of limb girdle syndrome. The most important electromyographic findings in patients with muscular atrophy are the neurogenic action potentials and fasciculations. Fibrillations, positive sharp waves and bizzare discharges may be found also in some patients with muscular dystrophy. Myogenic action potentials are found in some patients with muscular atrophy and so may cause confusion. Muscle biopsy may also reveal some myogenic features in patients with muscular atrophy. In conclusion electromyography and muscle biopsy are useful in the differentiation of different types of limb girdle syndrome, as well as, in determining the exact pattern of muscle involvement.

A patient with one limb interstitial myositis with localised lipoatrophy presenting with severe cramps and fasciculations.

A case of interstitial myositis associated with a localised lipoatrophy is reported. The patient is a 24 year old man who presented with severe painful cramps and fasciculations localised to one limb. The rarity of both disorders, and their likely common autoimmune mechanism, suggest that this is not a chance association.

AAEM minimonograph #37: facial and limb myokymia.

Myokymia is a clinical phenomenon associated with characteristic electromyographic activity referred to as myokymic discharges. These are spontaneously generated bursts of individual motor unit potentials with each burst recurring rhythmically or semirhythmically, usually several times per second. It involves facial muscles more commonly than those of the extremities, and is most often seen in association with Guillain-Barré syndrome, multiple sclerosis, radiation plexopathy, pontine tumors, and timber rattlesnake envenomation. An alteration in the biochemical microenvironment of axon membranes at one of the various sites along the motor axon is the likely basis for the altered membrane excitability that underlies the myokymic discharges in most cases. The similarity of these discharges to those seen with hypocalcemic tetany, and the ability to manipulate myokymic discharges by altering serum-ionized Ca++, suggests that decrease in the ionized Ca++ in the microenvironment of the axon may play an important role.

Cramp-fasciculation syndrome: a treatable hyperexcitable peripheral nerve disorder.

We report nine patients with muscle aching, cramps, stiffness, exercise intolerance, and peripheral nerve hyperexcitability. Neurologic examination showed calf fasciculations in seven, quadriceps myokymia in two, and deltoid myokymia in one patient. Two patients had mild increase in serum creatine kinase. Muscle biopsy showed either no abnormality (three patients) or mild neurogenic changes (four patients). Fasciculations were the only abnormality on routine electrodiagnostic studies. Supramaximal stimulation of the median, ulnar, peroneal, and posterior tibial nerves at frequencies of 0.5, 1, 2, and 5 Hz produced showers of electrical potentials following the M response in at least one nerve. In three patients, the fasciculations and evoked electrical potentials were abolished by regional application of curare but not nerve block. Carbamazepine therapy caused moderate-to-marked reduction of symptoms and nerve hyperexcitability. We designate this hyperexcitable peripheral nerve disorder as the "cramp-fasciculation syndrome."

Concurrence of myasthenia gravis and chorée fibrillaire de Morvan.

A case of myasthenia gravis associated with a syndrome resembling "chorée fibrillaire de Morvan" is described. This association has not been previously noted in the literature. It is postulated that this syndrome, when associated with myasthenia gravis, suggests an autoimmune pathogenesis, but prednisolone and plasmapheresis did not alter the symptoms. This case illustrates the fact that a separate entity should be considered when the clinical picture is not compatible with the underlying diagnosis.