What is a muscle twitch

Muscle twitches also called muscle fasciculation, are fine movements of a small area of your muscle. Muscle twitching is caused by minor muscle contractions in the area, or uncontrollable twitching of a muscle group that is served by a single motor nerve fiber.

Muscle twitches are minor and often go unnoticed. Some are common and normal. Others are signs of a nervous system disorder.

Most people get muscle twitches from time to time.

Muscle twitching are often linked to:

• stress and anxiety
• tiredness and exhaustion
• drinking caffeine or alcohol
• some medicines – check the side effects on the packet or leaflet

Muscle twitching can affect any part of the body. Twitches in the eyes or legs are particularly common.

You may also have tingling or cramps (spasms) in the same area.

Muscle twitching in healthy subjects is usually caused by coffee; exhaustive physical activity/fatigue; stress; cramp syndrome and benign twitches ¹.

Twitches not caused by disease or disorders (benign twitches), often affecting the eyelids, calf, or thumb. These twitches are normal and quite common, and are often triggered by stress or anxiety. These muscle twitches can come and go, and usually do not last for more than a few days.

No treatment is needed for benign muscle twitching in most cases. In other cases, treating an underlying medical cause may improve symptoms.

See your health care provider if you have long-term or persistent muscle twitches or if twitching occurs with weakness or loss of muscle.

How to stop muscle twitching

A muscle twitch may come and go, but will normally stop in a few days or weeks.

There isn’t usually any treatment for it.

There are some things you can do to help:

DO

• get plenty of rest
• try to find ways to relax
• stretch and massage any muscles affected by cramps
• try not to worry about it – a twitch is usually harmless, and worrying can make it worse

DON’T

• do not drink lots of caffeine, such as tea and coffee
• do not drink lots of alcohol
• do not stop taking a prescribed medicine without getting medical advice, even if you think it could be causing your twitch

Muscle twitching causes

Muscle twitching causes may include:

• Autoimmune disorders, such as Isaac syndrome.
• Drug overdose (caffeine, amphetamines, or other stimulants).
• Lack of sleep.
• Drug side effect (such as from diuretics, corticosteroids, or estrogens).
• Exercise (twitching is seen after exercise).
• Lack of nutrients in the diet (deficiency).
• Stress.
• Systemic diseases:
  • Hyperthyroidism;
  • Syndrome of inappropriate secretion of thyroid-stimulating hormone (TSH);
  • Hypophosphatemia, calcium disorders secondary to hyperparathyroidism.
• Medical conditions that cause metabolic disorders, including low potassium, kidney disease, and uremia.
• Drugs and/or intoxications by heavy metals pollutants:
  • Neostigmine;
  • Succinylcholine;
  • Elemental mercury intoxication;
  • Association of lithium and nortriptyline;
  • Flunarizine;
  • Isoniazid.
• Twitches not caused by disease or disorders (benign twitches), often affecting the eyelids, calf, or thumb. These twitches are normal and quite common, and are often triggered by stress or anxiety. These twitches can come and go, and usually do not last for more than a few days.

Nervous system conditions that can cause muscle twitching include ¹:

• Neuropathy or damage to the nerve that leads to a muscle
• Spinal muscular atrophy
• Weak muscles (myopathy)
• Motor neuron diseases:
  • Amyotrophic lateral sclerosis (ALS), also sometimes called Lou Gehrig disease;
  • Progressive spinal muscular atrophies;
  • Benign monomelic amyotrophy;
  • Post-polio syndrome;
  • Kennedy disease
• Muscle twitching associated with movement disorders:
  • Espino-cerebell,ar degeneration-type 3;
  • Espino-cerebellar degeneration-type 36;
  • Parkinsonisms (multiple system atrophy, ALS-plus syndromes)

Symptoms of a nervous system disorder include:

• Loss of, or change in, sensation
• Loss of muscle size (wasting)
• Weakness

Muscle twitching in healthy subjects

Muscle twitching can also be found in individuals with no neurological disease. In 1963, Reed and Kurland discovered that the presence of muscle twitching was not necessarily a prelude to the onset of a progressive and lethal disease, due to the involvement of the lower motor neuron ². Since then, several authors have explored this topic, defining a benign fasciculation syndrome (benign twitches), that most frequently affects young healthcare professionals ³, who, in some cases, have already developed dyspnea ⁴. An interesting Australian prospective study published recently examined the cases of 20 physicians (20 consecutive cases) complaining of muscle twitching ³. Fourteen of them were very concerned about being diagnosed with amyotrophic lateral sclerosis (ALS). The muscle twitching were mainly in the lower limbs, which had normal muscle strength. In the electrophysiological study, muscle twitching potentials were of the simple type, motor conduction was normal and no signs of denervation or neurogenic changes of motor units were apparent.

These authors, in agreement with others, concluded that physical exercise, stress, fatigue and caffeine abuse can precipitate or aggravate this picture. Among the other six individuals in the sample, five patients manifested a cramp-fasciculation syndrome (Denny-Brown syndrome) and only one suffered from amyotrophic lateral sclerosis (ALS).

Some authors have stated that, in order to establish the clinical diagnosis of benign twitches, a minimum of five years is necessary, due to the evolution, in some cases, of the motor neuron disease ⁵.

A work by Fermont et al. ⁶ reported the prevalence and distribution of muscle twitching in healthy adults. The potentials were studied by ultrasound in 58 individuals from different age groups. The subjects were also interviewed using questionnaires about the exacerbation of caffeine consumption and physical activity. Of the total sample, 43% had muscle twitching, especially in the hallucis longus abductor muscle. In the lower limbs, muscle twitching were rarely found and reported. Older individuals showed more muscle twitching than young adults. The authors have noted that certain physical activities, when very intense, may exacerbate symptoms in the lower limbs.

Muscle twitching associated with motor disorders

Although muscle twitching are not classified as a motor disorder, they are conceptually abnormal movements. Despite they are not rare, only a few studies investigate the association between muscle twitching and motor disorders ⁷.

In the cerebellum medullary degeneration type 3 (Machado-Joseph disease, spinocerebellar ataxia type 3 [SCA 3]), a dominant autosomal disease related to an unstable and increased expansion of the CAG trinucleotide, is often associated with cramps, muscle twitching and amyotrophy ⁸.

In a series of 50 cases of spinocerebellar ataxia type 3 (SCA 3) France et al. ⁹ observed muscle twitching in half of patients, most commonly in the facial region. Potential muscle twitching were noticed in conventional electromyography in 41 cases. The authors reported the involvement of the peripheral nerves.

Kanai and Kuwabara ¹⁰ posited that in spinocerebellar ataxia type 3 (SCA 3) the severity of cramps/muscle twitching correlates with peripheral axonal excitability, suggesting that the appearance of potentials is associated with subjacent axonal peripheral depletion and attempted sprouting of the remaining motor neurons for reinnervation of partially denervated muscles. Another cerebellar degeneration in which the ataxia is associated with muscle twitching is spinocerebellar ataxia type 3 (SCA 3) ¹¹. Recently described in Japanese families by Kobayashi et al. ¹², it is characterized by an increasing expansion of the hexanucleotide GGCCTG repeat in the first intron of the NOP56 gene.

Ikeda et al. ¹³ found that amyotrophy and muscle twitching affected the tongue of most of the 18 SCA36 patients, and in more than half of them, trunk and limbs were also affected. They detected the involvement of the lower motor neuron using electroneuromyography (ENMG). In the same period, García-Murias et al. ¹⁴ described spinocerebellar ataxia type 3 (SCA 3)6 in two families from the region of Galicia in Spain. However, the observed phenotype differed from the Japanese one, since it occurred in association with a cerebellar syndrome, a condition of sensorineural hearing loss and restriction of movement like fasciculation or myokymia, in addition to (small) amyotrophy in the tongue.

In certain situations, fasciculation potentials are associated with parkinsonisms. There are few reports of cases where such correlation is highlighted in the context of an atypical form of parkinsonism called multiple system atrophy (MSA). In an original article describing the Shy-Drager syndrome ¹⁵, a type of multiple system atrophy, the authors reported the coexistence, in the two cases described, of muscle twitching with dysautonomia, parkinsonism, cerebellar syndrome and other manifestations.

Montagna et al. ¹⁶ reported muscle twitching and amyotrophy in five cases of Shy-Drager syndrome. Clinical, electrophysiological, and anatomopathological examinations indicated the degenerative involvement of spinal previous ends.

In 2008, Luo et al. ¹⁷ described the case of a 68-year-old man, whose manifestations were muscle weakness, amyotrophy, muscle twitching, tremor and cerebellar syndrome. The electroneuromyography (ENMG) was consistent with spinal muscular atrophy (SMA) and olivopontocerebellar atrophy (OPCA), a type of multiple system atrophy, which was confirmed by the MRI results. As there were no other cases in the family of the patient, the authors reported this to be the first case of spinal muscular atrophy with sporadic olivopontocerebellar atrophy. Unlike muscle twitching, these are more frequent in patients with multiple system atrophy (MSA), myoclonus, myokymia, and involved particularly the face ¹⁸.

Machida et al. ¹⁹ reported a case of sporadic amyotrophic lateral sclerosis with multiple system degeneration found at necropsy. A 48-year-old man who died one year after the onset of the disease had muscular atrophy, weakness and muscle twitching in various body segments, ataxia and an increase of deep tendon reflexes in all four limbs in addition to rigidity and tremor. The necropsy showed a degeneration of the upper and lower motor neurons, the substantia nigra, the dentate nucleus and the locus coeruleus.

Under certain situations, muscle twitching are associated with parkinsonisms. However, this link cannot be considered in the presence of at least two aspects. The distinction between hypertonia is not always an easy task in clinical practice. Spasticity and rigidity can occur at the same time in a patient.

The pyramidal damage can be so intense that it is not possible to verify a plastic hypertonicity, even when this results from a severe impairment of the substantia nigra ²⁰. The other aspect is the bureaucratic interpretation of an excellent consensus for the diagnosis of amyotrophic lateral sclerosis and diseases that are similar to parkinsonism, as can be seen in the Brain Bank of the Parkinson’s Disease Society of the United Kingdom ²¹.

Inaccurate reading of guidelines such as these can cause the elimination of different cases, due to their lack of consistency with these criteria. As a result there is a lack of studies and reports of non-classical cases. The first references concerning the coexistence of signs of involvement of both the upper and the lower motor neurons and the parkinsonian syndromes date back to almost a century ago. In 1923, van Bertrand and van Bogaert reported the pathological involvement of the basal ganglia in patients with ALS. In 1926, Alajouanine described the existence of motion disorders in rare cases of Charcot disease. Subsequently, in 1959, van Bondelle and colleagues presented a case of a woman who suffered from Parkinson’s disease associated with ALS ²². More recent studies confirm the relationship between these disorders in experimental animals (transgenic mouse with super-oxide dismutase – GH1) based on brain scintigraphy with an assessment of the dopaminergic transmission ²⁰. Several syndromes, be them sporadic or hereditary, with the most diverse names have been described in relation to overlapping signs of parkinsonism, muscle twitching and amyotrophy. Symptoms and signs of parkinsonism, usually bradykinesia and axial rigidity, occur in 5 to 17% of ALS patients and often respond badly to the use of levodopa. In these patients, brain scintigraphy shows a decreased striatal dopaminergic function, while neuropathological studies reveal a neuronal loss in the substantia nigra and in the globus pallidus ²³. On the basis of El Escorial criteria they are classified as ALS-Plus Syndromes and ALS Mimic Syndromes in the presence of a parallel development of ALS and extrapyramidal signs ²¹. However, besides the fortuitous presence of extrapyramidal signs in the clinical course of some patients with ALS, it is likely that, in some conditions, Parkinson’s disease and ALS develop in the same individual from the same pathogenic pathway.

Park and colleagues ²⁴ found a decrease in the transportation of dopamine in the putamen of two patients who showed parkinsonian signs and diffuse and progressive involvement in the upper and lower motor neurons. In both, bradykinesia, rigidity and tremor were asymmetrical and responsive to levodopa and dopamine agonist. Both manifested bilateral pyramidal signs and amyotrophy with diffuse muscle twitching. In one, the signs of ALS preceded the Parkinson’s disease ones, while in the other the opposite occurred. The authors also noticed that the decrease in dopamine transportation, determined by a pre-synaptic dysfunction of the nigrostriatal pathway was more pronounced in the contralateral striatum than the parkinsonian signs and reported such cases as ALS with parkinsonism (ALS-D). A recent multicentric study ²², which evaluated 6,471 with ALS, 7668 controls and 3146 with Parkinson’s disease, found a correlation between gene variations in the gene for angiogenin in patients with ALS and signs of Parkinson’s disease and increased risk of developing Parkinson’s disease in relatives of patients with ALS and these variations. The authors suggest that these variations should be linked between the neurodegenerative process of ALS and Parkinson’s disease. Brait, Fahn and Shwartz ²⁵ described three patients who showed an uncommon disease. It was observed in them the occurrence of symptoms and signs consistent with Parkinson’s disease persistent to levodopa and the subsequent development (a few months to two years later) of ALS, in the absence of any other neurological signs or symptoms. Gilbert, Fahn, Mitsumoto and Rowland ²⁶ reviewed data from 5500 cases of parkinsonism documented by the Columbia University Division of Movement Disorders database and compared with data from Columbia University’s MDA/ALS Research Center. As search words parkinsonism and upper motor neuron (UMN), lower motor neuron (LMN) dysfunction, or both were used. Twenty-five patients were identified. Two patients treated by Prof. Lewis P. Rowald were added. Out of these 27 cases in total, 7 had a form of ALS-p called by the authors Brait-Fahn disease, though with minor differences compared to the initial description, whereas in 3 cases there was a cognitive disorder and in 1 there were cerebellar changes. There were also 4 cases of Frontotemporal Dementia whith ALS, 6 cases of multiple system atrophy with ALS and 3 with a potential hereditary spastic paraplegia in which parkinsonism occurred with signs of involvement of LMN with or without a UMN disorder. The authors did not specify in how many of these patients muscle twitching were assessed, given the fact that they are considered a sign of malfunction of the lower motor neuron, amyotrophy and/or fasciculation. Of the 23 cases with both parkinsonism and LMN signs, 11 showed an improvement with the use of levodopa. Manno et al. ²³, described 2 cases of Brait-Fahn-Schwartz disease in which progressive parkinsonian symptoms and signs preceded the appearance of ALS.

In these patients, SPECT with 1231-Ioflupane analysis revealed a bilateral reduced striatal uptake and genetic screening for SOD1, TDP-43, C9orf 72, FUS, angiogenin, Park-1, Park-2-Park and Park-6 7 (DJ-1) mutations were negative. In both the dopaminergic therapy (pramipexole and levodopa) was effective and long lasting in the treatment of Parkinsonian syndrome.

Annesi et al. ²⁷ described a family from Southern Italy with a double homozygous mutation in the DJ-1 gene and a rather complex phenotype. In two of the patients described, amyotrophy and diffuse myomuscle twitching coexisted with bilateral piramidalism, bradykinesia, tremor at rest, rigidity. Some of them also had dementia. The order of appearance of motor neuron disease and parkinsonism varied in both patients. The authors named these cases as Early Onset Parkinson disease/ALS. Under the heading of neuromyotonias, there are reports of the coexistence of involuntary movements with muscle twitching. This group is characterized by the occurrence of a failure of muscle relaxation and continuous muscle fiber activity. The most well-knonwn is the Isaacs Syndrome. This rare syndrome has several causes, such as neoplastic diseases, immune-mediated diseases, including para-neoplastic, hereditary and degenerative diseases. Furthermore, it is referred to as canulopatia due to loss of the voltage-dependent potassium channels function (VGKCs) damaged by antibodies. The failure of voltage-dependent potassium channels results in hyperexcitability of peripheral nerves and consequent continuous muscle fiber activity. Clinically, cramps are observed with muscle twitching, continuous involuntary muscle activity (clinical myokymia), stiffness, delayed muscle relaxation and hyperhidrosis.

In the electroneuromyography, spontaneous discharges of motor unit potentials are detected during the needle test, which appear as generalized myokymia or neuromiotonic discharges.

In Morvan Syndrome (Morvan’s fibrillary chorea), another neuromyotonia even more unusual in which an hyperactivity in the central nervous systems (mental confusion, disturbances mnésticos, hallucinations, insomnia and myoclonus) coexist with peripheral symptoms (neuromyokymias), the combination of muscle twitching and movement disorder is controversial. There are few reports. Deymeer et al. ²⁸ describe muscle twitching and tremor in a case of Morvan Syndrome associated with thymoma, whereas Irani et al. ²⁹ do not mention fasciculation in any of the patients in a series of 29 cases with Morvan (11 manifested thymoma).

Muscle twitching in motor neuron diseases

Numerous motor neuron diseases occur with muscle twitching ³⁰, such as Progressive Spinal Muscular Atrophies, Amyotrophic Lateral Sclerosis, Benign Monomelic Amyotrophy, Post-Polio Syndrome, Kennedy’s disease, among others. With respect to ALS, there are few studies that describe the early changes in the motor unit and the pathophysiological aspects both in the initial stage and along the natural course of disease ³¹. For this purpose De Carvalho and Swash ³² studied the neurophysiological aspects of the anterior tibialis muscle (TA) in 73 ALS patients during the disease progression. Of these, 61 had a normal muscle strength (Medical Research Council: 5) in anterior tibialis muscle and 12 a moderate paresis (Medical Research Council: 4). They also evaluated the potential presence of muscle twitching and fibrillations/sharp-waves (fibs-sw), and quantified muscle unit potentials (MUPs) and jitter. ALS patients with a normal strength in the anterior tibialis muscle were investigated in serial studies. Fasciculation potentials were recorded in the anterior tibialis muscle (Medical Research Council: 5) in 21 patients with ALS and normal motor unit potentials. Longitudinal studies confirmed that the patients presenting fasciculation potentials as the only abnormality progressed to muscle unit potentials (MUPs) instability before large motor unit potentials associated with fibs-sw were detected. The complexity of muscle twitchings in patients with weak tibialis anterior muscle was greater than in the latter group. The authors consider the potential of an early marker in muscle twitching (ALS), which undoubtedly anticipates instability of motor unit potentials or the re-innervation process. This finding can be seen in the early stages of the disease, in which axonal excitability is increased. With disease progression neuronal dysfunction occurs with loss of motor unit potentials and a transitional process of compensatory re-innervation.

Deficits in neuromuscular transmission are considered one of the most important signs in the pathophysiology of ALS. Among them fasciculation potentials are almost always identified during the clinical and neurophysiological examination, since, according to some authors, they originate in peripheral axons. It is postulated that the dysfunction of potassium channels in axons of ALS patients evokes hyperexcitability of the membrane (axonal), which show potential muscle twitching. An important fact is that the magnetic cortical stimulation can evoke the same potential muscle twitching, corroborating the idea that such hyperexcitability may be present in both with the depletion of spinal motor neurons as cortical (pyramidal tract). After analyzing 2681 fasciculation potentials in 17 patients with ALS, Hirota et al. ³³ also supports the theory that the origin of muscle twitching is combined. According to the authors, supraspinal segments have contributed to the onset of the process. All these findings suggest that involvement affects both the central and the peripheral system in ALS ³⁴. Such considerations may explain in part why patients with peripheral nerve injuries and\or first motor neuron lesions may present potential muscle twitching, although not very frequently.

Muscle twitching induced by systemic diseases, drugs and/or intoxication by heavy metals

Thyroid disorders such as hyperthyroidism and inappropriate secretion of thyrotropin syndrome (TSH) can also trigger muscle twitching. Similarly, hypophosphatemia and calcium disorders secondary to hyperparathyroidism can sometimes cause the same ³⁵. With regard to pharmacological treatments, in a pioneering experimental study Wigiton and Masland ¹¹ concluded that neostigmine may cause muscle twitching potentials by increasing the concentration of acetylcholine in the neuromuscular junction in felines. Discharges are caused by the direct effect of acetylcholine on motor nerve terminals. Moreover, due to a similar mechanism, the same occurs during the induction of anesthesia with succinylcholine by endotracheal tube ³⁶.

Finelli described an interesting case under the title of Drug-Induced Creutzfeldt-Jakob-like Syndrome ³⁷. An elderly manifested rapidly progressive dementia, postural tremor, gait instability, myoclonus and muscle twitching caused by a combination of lithium and nortriptyline. Postural tremor, multifocal myoclonus, amyotrophy and muscle twitching were also reported in a woman treated with topiramate for migraine without aura. Orsini et al. ³⁸ also presented a case of muscle twitching caused by oral corticosteroids at immunosuppressive doses in patients with immune-mediated kidney disease.

Adams et al. ³⁹ described the case of a 54-year-old man who presented a ALS-like condition after a brief, but intense exposure to elemental mercury. After the fall of mercury serum levels, the clinic signs ceased completely. The toxicity of mercury should be considered not only in subjects with recent dysfunction of cells of the anterior horn of the spinal cord, but also with conditions like peripheral neuropathies of unknown origin, tremor, ataxia, and a range of psychiatric symptoms including confusion and depression.

Shinkeigaku et al. ⁴⁰ presented a case (21-year-old man) of anti VGKC-complex antibody associated with a disorder presenting severe pain and muscle twitching that predominantly in a single upper extremity. Recently also isoniazid and flunarizine have been considered a potential source of muscle twitching ⁴¹.

Muscle twitching diagnosis

Your doctor will take a medical history and perform a physical exam.

Medical history questions may include:

• When did you first notice the twitching?
• How long does it last?
• How often do you experience twitching?
• What muscles are affected?
• Is it always in the same location?
• Are you pregnant?
• What other symptoms do you have?

Tests depend on the suspected cause, and may include:

• Blood tests to look for problems with electrolytes, thyroid gland function, and blood chemistry
• CT scan of the spine or brain
• Electromyogram (EMG)
• Nerve conduction studies
• MRI scan of the spine or brain

Muscle twitching treatment

Muscle twitching describes a symptom of fine movements of a small area of your muscle and not a diagnosis of a disease. Muscle twitching refers to sudden, involuntary jerking of a muscle or group of muscles. Muscle twitching is caused by minor muscle contractions in the area, or uncontrollable twitching of a muscle group that is served by a single motor nerve fiber. Specific treatment for muscle twitching is to treat the underlying cause of the muscle twitching. The use of antiepileptic drugs such as carbamazepine and phenytoin has shown a partial therapeutic response. Gabapentin can also be used generally at low doses from 300 to 600 mg ⁴². However, due to their benign and transitional nature, it is not always necessary to treat muscle twitching. A recent study proposed a new approach to treat the muscle cramps and benign muscle twitching through the identification and correction of sleep apnea, which in most cases can be one of the triggers ⁴³. Meanwhile, one should be aware of the diagnosis, rule out the possibility of other neurological diseases and look for less obvious causes or the presence of systemic diseases, sometimes decompensated, for example, thyroid disorders and electrolyte abnormalities. Also one should watch for adverse effects to drugs, whose correction and control will allow an adequate therapeutic response. Since no specific drug has yet been identified to treat these disorders, a regular clinical monitoring should be performed for some time before formulating the diagnosis. Considering the wide pathophysiological skeletal involvement in the genesis of muscle twitching, first it is necessary to identify their origin and then the therapeutic target.

1. Leite MA, Orsini M, de Freitas MR, et al. Another Perspective on Fasciculations: When is it not Caused by the Classic form of Amyotrophic Lateral Sclerosis or Progressive Spinal Atrophy?. Neurol Int. 2014;6(3):5208. Published 2014 Aug 8. doi:10.4081/ni.2014.5208 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4192433/
2. Reed DM, Kurland LT. Muscle fasciculations in a healthy population. Arch Neurol 1963;9:363-7
3. Simon NG, Kiernan MC. Fasciculations anxiety syndrome in clinicians. J Neurol 2013;260:1743-7
4. Rigby J, Holton A, Partridge J, Satchithananda D. Dyspnoea fasciculations syndrome: the clue is in the title. BMJ Case Rep 2012:2012
5. Singh V, Gibson J, McLean B, et al. Fasciculationss and cramps: how benign? Report of four cases progressing to ALS. J Neurol 2011;258:573-8
6. Fermont J, Arts IM, Overeem S, et al. Prevalence and distribution of fasciculationss in healthy adults: effect of age, caffeine consumption and exercise. Amyotroph Lateral Scler 2010;11:181-6
7. Arias M, Arias-Rivas S, Blanco-Arias P, et al. [SCA from the Costa da Morte: A new SCA. Description of the phenotype]. Neurologia 2008;23:628-9
8. Tan EK, Tong J, Pavanni R, et al. Genetic analysis of SCA 2 and 3 repeat expansions in essential tremor and atypical Parkinsonism. Mov Disord 2007;22:1971-4
9. França MC, Jr, D’Abreu A, Nucci A, Lopes-Cendes I. Muscle excitability abnormalities in Machado-Joseph disease. Arch Neurol 2008;65:525-9
10. Kanai K, Kuwabara S. Motor nerve hyper-excitability and muscle cramps in Machado-Joseph disease. Arch Neurol 2009;66:138-141
11. Masland RL, Wigiton RS. Nerve activity accompanying fasciculations produced by prostigmin. J Neurophysiol 1940;3:269-75
12. Kobayashi H, Abe K, Matsuura T, et al. Expansion of Intronic GGCCTG hexanucleotide repeat in NOP56 causes SCA36, a type of spinocerebellar ataxia accompanied by motor neuron involvement. Am J Hum Genet 2011;89:121-30
13. Ikeda Y, Ohta Y, Kobayashi H, et al. Clinical features of SCA36: a novel spinocerebellar ataxia with motor neuron involvement (Asidan). Neurology 2012;79:333-41
14. García-Murias M, Beatriz Quintáns B, Arias M, et al. Costa da Morte ataxia is spinocerebellar ataxia 36: clinical and genetic characterization. Brain 2012:135; 1423-35
15. Shy GM, Drager GA. A neurological syndrome associated with orthostatic hypotension: a clinical-pathologic study. Arch Neurol 1960;2:511-27
16. Montagna P, Martinelli P, Rizzuto N, et al. Amyotrophy in Shy-Drager syndrome. Acta Neurol Belg 1983;83:142-57
17. Luo W, Ouyang Z, Guo Y, et al. Spinal muscular atrophy combined with sporadic olivopontocerebellar atrophy. Clin Neurol Neurosurg 2008;110:855-8
18. Blunt SB, Khalil NM, Perkin GD. Facial myokymia in multiple system atrophy. Mov Disord 1997;12:235-8
19. Machida Y, Tsuchiya K, Anno M, et al. Sporadic amyotrophic lateral sclerosis with multiple system degeneration: a report of an autopsy case without respirator administration. Acta Neuropathol 1999;98:512-5
20. Le Forestier N, Lacomblez L, Meininger V. Syndromes parkinsoniens et scléroselatéraleamyotrophique: Tauopathies, TDP-43 et mutations SOD. Rev Neurol (Paris) 2009;165:15-30
21. Brooks BR, Miller RG, Swash M, et al. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 2000;1:293-9
22. van Es MA, Schelhaas HJ, van Vught PW, et al. Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis. Ann Neurol 2011;70:964-73
23. Manno C, Lipari A, Bono V, et al. Sporadic Parkinson disease and Amyotrophic Lateral Sclerosis complex (Brait-Fahn-Schwartz Disease). J Neurol Sci 2013;326:104-6
24. Park HK, Lim YM, Kim JS, et al. Nigrostriatal dysfunction in patients with amyotrophic lateral sclerosis and parkinsonism J Neurol Sci 2011;301:12-3
25. Brait K, Fahn S, Schwarz GA. Sporadic and familial parkinsonismand motor neuron disease. Neurology 1973;23:990-002
26. Mills KR. Characteristics of fasciculationss in amyotrophic lateral sclerosis and the benign fasciculations syndrome. Brain 2010;133:3458-69
27. Annesi G, Savettieri G, Pugliese P, et al. DJ-1 mutations and parkinsonism-dementia-amyotrophic lateral sclerosis complex. Ann Neurol 2005;58:803-7
28. Deymeer F, Akca S, Kocaman G, et al. Fasciculationss, autonomicsymptoms and limbic encephalitis: a thymoma-associated Morvan’s-like syndrome. Eur Neurol 2005;54:235-7
29. Irani SR, Pettingill P, Kleopa KA, et al. Morvansyndrome: clinical and serological observations in 29 cases. Ann Neurol. 2012,72:241-55
30. Krivickas LS. Amyotrophic lateral sclerosis and other motor neuron diseases. Phys Med Rehabil Clin N Am 2003;14:327-45
31. Higashihara M, Sonoo M. [Electrodiagnosis of ALS]. Brain Nerve 2007;59:1031-41
32. de Carvalho M, Swash M. Fasciculations potentials and earliest changes in motor unit physiology in ALS. J Neurol Neurosurg Psychiatry 2013;84:963-8
33. Hirota N, Eisen A, Weber M. Complex fasciculationss and their origin in amyotrophic lateral sclerosis and Kennedy’s disease. Muscle Nerve 2000;23:1872-5
34. Kohara N. Abnormal hyperexcitability in ALS. Rinsho Shinkeigaku 1999;39:61-4
35. Godoy JM, Oliveira MAR, Moraes Neto JBM, et al. Esclerose lateral amiotrófica esporádica. Critérios diagnósticos. Arq Neuropsiquiatr 1993;51:236-42
36. Muravchick S, Burkett L, Gold MI. Succinycholine-induced fasciculationss and intragastric pressure during induction of anesthesia. Anesthesiology 1981;55: 180-3
37. Finelli PF. Drug-induced Creutzfeldt-Jakob like syndrome. J Psychiatr Neurosci 1992;17:103-5
38. Orsini M, Sztajnbok FR, Oliveira AB, et al. Benign fasciculationss and corticosteroid use: possible association? An update. Neurol Int 2011;3:e11
39. Adams CR, Ziegler DK, Lin JT. Mercury intoxication simulating amyotrophic lateral sclerosis. JAMA 1983;250:642-3
40. Hara K, Watanabe O, Shibano K, Ishiguro H. [A case of anti VGKC-complex antibody associated disorder presenting with severe pain and fasciculations predominant in unilateral upper extremity]. Rinsho Shinkeigaku 2012; 52(9):677-80
41. Kizilay F, Ekmekci B, Gungor H, et al. Flunarizine-induced fasciculations-myokymia. J Clin Neuromuscul Dis 2011; 12:246-7
42. Buainain RP, Souza Moura L, Oliveira ASB. Fasciculations. Rev Neurocienc 2000;8:31-4
43. Reddy PL, Grewal RP. Resolution of muscle cramps and fasciculations with treatment of sleep apnea. J Clin Neuromuscul Dis 2009;11:66-7