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Neural Disorders of Skeletal Muscle Overactivity: Cramps and Fasciculations, Neuromyotonia, Tetanus, Tetany, Satayoshi, and Stiff-Person Syndrome
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Complaints of muscle pain and stiffness are a common and confounding occurrence in the practice of medicine Muscle cramping, tenderness, involuntary limb movement and posturing, fatigue, and exercise intolerance frequently occur in unison Conceptualization of the disorders that produce these symptoms is dif cult for a number of reasons Most of these complaints are nonspeci c, de ning neither disease locus, pathogenetic mechanism nor etiology The principles of neurological localization are dif cult to apply to these disorders Distinction between intracranial, spinal, neuronal cell body, axon, or muscle as the site of symptom origin is not readily accomplished through assimilation and formulation of clinical clues Despite extensive evaluation, a large proportion of these individuals with symptoms referable to muscle discomfort and undesired muscle activity defy diagnosis Some of the disorders that present with ill-timed, excessive, and unwanted muscle activity not of neural origin are addressed in other chapters of this book Disorders of muscle producing physiologic contracture, myotonia, and rippling muscle disease are considered in s 24, 26, and 29 Spasticity as the primary manifestation of corticospinal tract pathology is touched upon brie y in s 4 and 5, devoted to the discussion of ALS and hereditary spastic paraparesis Disorders of abnormal muscle posture and tone related to disorders of extrapyramidal system are not considered in this text This chapter is devoted to disorders of diverse cause that have the shared characteristic of unwanted muscular activity due to altered function of motor axons or their cell bodies The discussion will include cramps, which are commonplace and associated with either benign or sinister implication The cramp fasciculation syndrome may represent an intermediate disorder between muscle cramps and neuromyotonia Although initiated by different mechanisms, tetanus and stiff-person syndrome (SPS) share a common pathophysiology, that being impaired function of inhibitory spinal motor interneurons resulting in motor neuron hyperactivity As such, these are considered here, along with cramps, in the section on motor neuron diseases Neuromyotonia, also known as Isaac syndrome (IS), is considered to be a disorder of peripheral nerve In many cases, circulating antibodies speci c for voltage-gated potassium channels (VGKCs) can be demonstrated in the serum of patients who are affected, suggesting an autoimmune etiology Satoyoshi syndrome (SS) is another rare disorder, characterized by painful muscle spasms Little is known of its pathogenesis, but there is reason to believe that it too is an autoimmune disorder associated with disordered spinal inhibition
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Cramps are sudden, involuntary, and painful shortening of muscle accompanied by a squeezing sensation and visible, palpable muscle hardening Often, there is associated abnormal posturing of joints Cramps are relieved by massage or stretching They have a tendency to recur if the muscle is prematurely returned to its unstretched position They spontaneously remit within minutes without continued provocation Cramps are ubiquitous and are most commonly associated with a benign etiology Their weekly prevalence in a normal population is estimated at 35%1 They occur with greater frequency in the elderly and in pregnant females, as well as in those who have
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recently begun unaccustomed exercise Familial, benign cramp syndromes have been reported The gastrocnemius/soleus complex is the most common location of benign cramps, particularly in the elderly at night They are often elicited in the EMG laboratory, while trying to activate the gastrocnemius soleus complex Even if benign in etiology, cramps may provide signi cant morbidity if persistent Cramps are less commonly associated with potentially serious neuromuscular pathology Although they may associate with disorders of any level of the motor unit, their most notorious association is with the motor neuron (ie, anterior horn cell) diseases Cramps are common in ALS although are rarely a major complaint or source of morbidity These are commonly provoked during isometric manual muscle testing in these patients They occur in other lower motor neuron disorders affecting either anterior horn cells, eg, Kennedy s disease where these may represent the earliest symptom, or motor axons such as multifocal motor neuropathy2 4 Exertional cramping or contracture may occur in muscle disease as well They occur most commonly with metabolic disorders of muscle associated with disorders of glycogen, lipid, or mitochondrial metabolism They may represent an uncommon phenotype of the x-linked Becker s muscular dystrophy5 Fasciculations represent the random spontaneous discharge of all muscle bers belonging to a given motor unit These may or may not be felt or seen by a patient As in cramps, these have a frequently benign, although occasionally ominous, etiology As in cramps, they are more likely to be benign when con ned to a singular muscle belly at any given period of time or when they occur in isolation6 Cramps and fasciculations together or fasciculations occurring in multiple muscles/limbs simultaneously are disconcerting Fasciculation potentials represent the electrodiagnostic signature of fasciculations The clinical approach to cramps and fasciculations involves identifying other potential clues of an underlying disease Chronological association with a new drug exposure or any potential metabolic disturbance should be sought for (Table 8 1) Cramps occurring in isolation, particularly if isolated to the calf muscles, are frequently benign Conversely, cramps that are multifocal or occur in association with muscle weakness, atrophy, hypertrophy, muscle rippling, or chronic elevations of resting serum creatine kinase are more likely to represent an expression of an underlying neuromuscular disorder Electrodiagnosis is frequently used to identify or exclude evidence of an associated neuromuscular disorder
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
Ethanol Nifedipine Cimetidine Terbutaline Salbutamol Clo brate Penicillamine Hypothyroidism Hypoadrenalism Cirrhosis Diuretics Pregnancy Uremia/hemodialysis Intensive exercise/excessive sweating Diarrhea Emesis
Adapted with permission from Miller TM, Layzer RB Muscle cramps Muscle Nerve 2005;32:431 442
otherwise healthy people Despite the seemingly benign nature of the syndrome, eight of original nine reported cases were vocationally disabled7 Its classi cation remains in ux and its acceptance as a unique syndrome is not universal It may represent nothing more than a more severe expression of the benign cramps and fasciculations mentioned above On the opposite extreme, circulating anti-voltage-gated K+ channel antibodies have been demonstrated in the serum of some patients with this disorder, suggesting that it may be a limited expression of neuromyotonia8,9
In 1961, Isaacs described two patients with a history of progressive muscle stiffness associated with continuous muscle ber activity10 This syndrome has been referred to by a number of names including IS, the syndrome of continuous muscle ber activity, generalized myokymia, and acquired neuromyotonia Generalized myokymia term emphasizes both the neural origin of the abnormality and the pseudomyotonic muscle contraction that differentiates it from clinical myokymia The latter refers to a phenotype in which undulating waves of muscular rippling without the stiffness, contraction, and occasional abnormal posturing that help de ne the clinical syndrome of neuromyotonia8,11,12 Clinical manifestations of IS include a combination of diffuse muscle stiffness, widespread and continuous muscle twitching (clinical myokymia), and cramps13 Abnormal posturing may occur including carpopedal spasm, plantar exion
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