Neuromyotonia
Encyclopedia
Neuromyotonia also known as Isaacs' syndrome, is a form of peripheral nerve hyperexcitability that causes spontaneous muscular
activity resulting from repetitive motor unit action potentials of peripheral origin.
1) Acquired
2) Paraneoplastic
3) Hereditary
The acquired form is the most common accounting for up to 80 percent of all cases and is suspected to be autoimmune mediated, which is usually caused by antibodies
against neuromuscular junction.
The exact cause is unknown. However, autoreactive antibodies can be detected in a variety of peripheral (e.g. myasthenia gravis
, Lambert-Eaton myasthenic syndrome
) and central nervous system (e.g. paraneoplastic cerebellar degeneration
, paraneoplastic limbic encephalitis) disorders. Their causative role has been established in some of these diseases but not all. Neuromyotonia is considered to be one of these with accumulating evidence for autoimmune origin over the last few years. Autoimmune neuromyotonia is typically caused by antibodies that bind to potassium channels on the motor nerve resulting in continuous/hyper-excitability. Onset is typically seen between the ages of 15-60, with most experiencing symptoms before the age of 40. Some neuromyotonia cases do not only improve after plasma
exchange but they may also have antibodies in their serum
samples against voltage-gated potassium channel
s. Moreover, these antibodies have been demonstrated to reduce potassium channel function in neuronal cell lines.
-like symptoms (slow relaxation), hyperhidrosis (excessive sweating), myokymia
(quivering of a muscle), fasciculation
s (muscle twitching), fatigue, exercise intolerance and other related symptoms. The symptoms (especially the stiffness and fasciculations) are most prominent in the calves, legs, trunk, and sometimes the face and neck, but can also affect other body parts. NMT symptoms may fluctuate in severity and frequency. Symptoms range from mere inconvenience to debilitating (rare). At least a third of people also experience sensory symptoms.
1) Chronic
2) Monophasic (symptoms that resolve within several years of onset; postinfection, postallergic)
3) Relapsing Remitting
From there, you are likely to be referred to a neurologist or a neuromuscular specialist. The neurologist or a neuromuscular specialist may run a series of more specialized tests, including EMG/NCS (this is one of the most important tests), chest CT (to rule out paraneoplastic) and specific blood work looking for voltage-gated potassium channel antibodies, acethlocholine receptor antibody, and serum immunofixation, TSH, ANA ESR, EEG etc. Neuromyotonia is characterized electromyographically by doublet, triplet or multiplet single unit discharges that have a high, irregular intraburst frequency. Fibrillation
potentials and fasciculations are often also present with electromyography
.
Because the condition is so rare, it can often be years before correct diagnosis is made. Once diagnosis is made, rest assured that NMT condition is not fatal and can be controlled.
However, NMT does mimic some symptoms of motor neuron disease (ALS) and other more severe diseases, which is fatal. This can often lead to significant anxiety until diagnosis is made, which often exacerbates the symptoms of NMT. In some rare cases, acquired neuromyotonia has been misdiagnosed as amyotrophic lateral sclerosis (ALS) particularly if fasciculations may be evident in the absence of other clinical features of ALS. However, fasciculations are rarely the first sign of ALS as the hallmark sign is weakness. In order to get an accurate diagnosis see a trained neuromuscular specialist.
, Cramp Fasciculation Syndrome
, and neuromyotonia. Some doctors will only give the diagnosis of peripheral nerve hyperexcitability as the differences between the three are largely a matter of the severity of the symptoms and can be subjective. However, some objective EMG criteria have been established to help distinguish between the three.
Moreover, the generic use of the term "peripheral nerve hyperexcitability syndromes" to describe the aforementioned conditions is recommended and endorsed by several prominent researchers and practitioners in the field. (http://brain.oxfordjournals.org/cgi/reprint/125/8/1887.pdf)
and carbamazepine
, usually provide significant relief from the stiffness, muscle spasms, and pain associated with neuromyotonia. Plasma exchange and IVIg treatment may provide short-term relief for patients with some forms of the acquired disorder. It is speculated that the plasma exchange causes an interference with the function of the voltage-dependent potassium channels, one of the underlying issues of hyper-excitability in autoimmune neuromyotonia. Botox injections also provide short-term relief. Immunosuppressants, such as prednisone may provide long term relief for patients with some forms of the acquired disorder.
While NMT symptoms may fluctuate, they generally don't deteriorate into anything more serious and with the correct treatment the symptoms are manageable.
A very small proportion of cases with NMT may develop central nervous system findings in their clinical course, causing a disorder called Morvan's syndrome
and they may also have antibodies against potassium channels in their serum samples. Sleep disorder
is only one of a variety of clinical conditions observed in Morvan's syndrome cases ranging from confusion and memory loss to hallucination
s and delusion
s. However, this is a separate disorder.
Also, some studies have linked NMT with certain types of cancers, mostly lung and thymus, suggesting that NMT may be paraneoplastic in some cases. In these cases the underlying cancer will determine prognosis. However, most cases of NMT are autoimmune and not associated with cancer.
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
activity resulting from repetitive motor unit action potentials of peripheral origin.
Causes
The three causes of NMT are:1) Acquired
2) Paraneoplastic
3) Hereditary
The acquired form is the most common accounting for up to 80 percent of all cases and is suspected to be autoimmune mediated, which is usually caused by antibodies
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
against neuromuscular junction.
The exact cause is unknown. However, autoreactive antibodies can be detected in a variety of peripheral (e.g. myasthenia gravis
Myasthenia gravis
Myasthenia gravis is an autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatiguability...
, Lambert-Eaton myasthenic syndrome
Lambert-Eaton myasthenic syndrome
Lambert–Eaton myasthenic syndrome is a rare autoimmune disorder that is characterised by muscle weakness of the limbs...
) and central nervous system (e.g. paraneoplastic cerebellar degeneration
Paraneoplastic cerebellar degeneration
Paraneoplastic cerebellar degeneration is a paraneoplastic syndrome associated with lung, ovarian, breast, and other cancers.As is the case with other paraneoplastic syndromes, PCD is believed to be due to an autoimmune reaction targeted against components of the central nervous system...
, paraneoplastic limbic encephalitis) disorders. Their causative role has been established in some of these diseases but not all. Neuromyotonia is considered to be one of these with accumulating evidence for autoimmune origin over the last few years. Autoimmune neuromyotonia is typically caused by antibodies that bind to potassium channels on the motor nerve resulting in continuous/hyper-excitability. Onset is typically seen between the ages of 15-60, with most experiencing symptoms before the age of 40. Some neuromyotonia cases do not only improve after plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
exchange but they may also have antibodies in their serum
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
samples against voltage-gated potassium channel
Voltage-gated potassium channel
Voltage-gated potassium channels are transmembrane channels specific for potassium and sensitive to voltage changes in the cell's membrane potential. During action potentials, they play a crucial role in returning the depolarized cell to a resting state....
s. Moreover, these antibodies have been demonstrated to reduce potassium channel function in neuronal cell lines.
Presentation/Symptoms
NMT is a diverse disorder. As a result of muscular hyperactivity patients may present with muscle cramps, stiffness, myotoniaMyotonia
Myotonia is a symptom of a small handful of certain neuromuscular disorders characterized by the slow relaxation of the muscles after voluntary contraction or electrical stimulation. Generally, repeated effort is needed to relax the muscles, and the condition improves after the muscles have warmed...
-like symptoms (slow relaxation), hyperhidrosis (excessive sweating), myokymia
Myokymia
Myokymia, is an involuntary, spontaneous, localized quivering of a few muscles bundles within a muscle, but which are insufficient to move a joint.One type is superior oblique myokymia....
(quivering of a muscle), fasciculation
Fasciculation
A fasciculation , or "muscle twitch", is a small, local, involuntary muscle contraction and relaxation visible under the skin arising from the spontaneous discharge of a bundle of skeletal muscle fibers...
s (muscle twitching), fatigue, exercise intolerance and other related symptoms. The symptoms (especially the stiffness and fasciculations) are most prominent in the calves, legs, trunk, and sometimes the face and neck, but can also affect other body parts. NMT symptoms may fluctuate in severity and frequency. Symptoms range from mere inconvenience to debilitating (rare). At least a third of people also experience sensory symptoms.
Types
There are three main types of NMT:1) Chronic
2) Monophasic (symptoms that resolve within several years of onset; postinfection, postallergic)
3) Relapsing Remitting
Diagnosis
Diagnosis is clinical and initially consists of ruling out more common conditions, disorders, and diseases, and usually begins at the general practitioner level (your primary doctor). You doctor may conduct a basic neurological exam, including coordination, strength, reflexes, sensation, etc. Your doctor may also run a series of tests that include blood work and MRIs.From there, you are likely to be referred to a neurologist or a neuromuscular specialist. The neurologist or a neuromuscular specialist may run a series of more specialized tests, including EMG/NCS (this is one of the most important tests), chest CT (to rule out paraneoplastic) and specific blood work looking for voltage-gated potassium channel antibodies, acethlocholine receptor antibody, and serum immunofixation, TSH, ANA ESR, EEG etc. Neuromyotonia is characterized electromyographically by doublet, triplet or multiplet single unit discharges that have a high, irregular intraburst frequency. Fibrillation
Fibrillation
Fibrillation is the rapid, irregular, and unsynchronized contraction of muscle fibers. An important occurrence is with regards to the heart.-Cardiology:There are two major classes of cardiac fibrillation: atrial fibrillation and ventricular fibrillation....
potentials and fasciculations are often also present with electromyography
Electromyography
Electromyography is a technique for evaluating and recording the electrical activity produced by skeletal muscles. EMG is performed using an instrument called an electromyograph, to produce a record called an electromyogram. An electromyograph detects the electrical potential generated by muscle...
.
Because the condition is so rare, it can often be years before correct diagnosis is made. Once diagnosis is made, rest assured that NMT condition is not fatal and can be controlled.
However, NMT does mimic some symptoms of motor neuron disease (ALS) and other more severe diseases, which is fatal. This can often lead to significant anxiety until diagnosis is made, which often exacerbates the symptoms of NMT. In some rare cases, acquired neuromyotonia has been misdiagnosed as amyotrophic lateral sclerosis (ALS) particularly if fasciculations may be evident in the absence of other clinical features of ALS. However, fasciculations are rarely the first sign of ALS as the hallmark sign is weakness. In order to get an accurate diagnosis see a trained neuromuscular specialist.
Peripheral Nerve Hyperexcitability
Neuromyotonia is a type of peripheral nerve hyperexcitability. Peripheral nerve hyperexcitability is an umbrella diagnosis that includes (in order of severity of symptoms from least severe to most severe) Benign Fasciculation SyndromeBenign fasciculation syndrome
Benign fasciculation syndrome is a neurological disorder characterized by fasciculation of various voluntary muscles in the body. The twitching can occur in any voluntary muscle group but is most common in the eyelids, arms, legs, and feet. Even the tongue may be affected. The twitching may be...
, Cramp Fasciculation Syndrome
Cramp Fasciculation Syndrome
Cramp fasciculation syndrome is a rare peripheral nerve hyperexcitability disorder. It is more severe than the related and common disorder known as benign fasciculation syndrome, causing fasciculations, cramps, pain, fatigue, and muscle stiffness similar to those seen in neuromyotonia, another...
, and neuromyotonia. Some doctors will only give the diagnosis of peripheral nerve hyperexcitability as the differences between the three are largely a matter of the severity of the symptoms and can be subjective. However, some objective EMG criteria have been established to help distinguish between the three.
Moreover, the generic use of the term "peripheral nerve hyperexcitability syndromes" to describe the aforementioned conditions is recommended and endorsed by several prominent researchers and practitioners in the field. (http://brain.oxfordjournals.org/cgi/reprint/125/8/1887.pdf)
Treatments
There is no known cure for neuromyotonia, but the condition is treatable. Anticonvulsants, including phenytoinPhenytoin
Phenytoin sodium is a commonly used antiepileptic. Phenytoin acts to suppress the abnormal brain activity seen in seizure by reducing electrical conductance among brain cells by stabilizing the inactive state of voltage-gated sodium channels...
and carbamazepine
Carbamazepine
Carbamazepine is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia...
, usually provide significant relief from the stiffness, muscle spasms, and pain associated with neuromyotonia. Plasma exchange and IVIg treatment may provide short-term relief for patients with some forms of the acquired disorder. It is speculated that the plasma exchange causes an interference with the function of the voltage-dependent potassium channels, one of the underlying issues of hyper-excitability in autoimmune neuromyotonia. Botox injections also provide short-term relief. Immunosuppressants, such as prednisone may provide long term relief for patients with some forms of the acquired disorder.
Prognosis
The long-term prognosis for individuals with the disorder is uncertain, and this has mostly to do with the etiology (underlying cause; i.e. autoimmune, paraneoplastic, etc.) and lack of research for this disorder. However, in recent years our increased understanding of the basic mechanisms of NMT and autoimmunity has led to the development of novel treatment strategies. NMT disorders are now amenable to treatment and their prognoses are good. Many patients respond well to treatment, which usually provide significant relief of symptoms. Some cases of spontaneous remission have been noted, including the original two Issacs patients when followed up 14 years later.While NMT symptoms may fluctuate, they generally don't deteriorate into anything more serious and with the correct treatment the symptoms are manageable.
A very small proportion of cases with NMT may develop central nervous system findings in their clinical course, causing a disorder called Morvan's syndrome
Morvan's syndrome
Morvan’s Syndrome, or Morvan’s fibrillary chorea , is a rare autoimmune disease named after nineteenth century French physician Augustin Marie Morvan...
and they may also have antibodies against potassium channels in their serum samples. Sleep disorder
Sleep disorder
A sleep disorder, or somnipathy, is a medical disorder of the sleep patterns of a person or animal. Some sleep disorders are serious enough to interfere with normal physical, mental and emotional functioning...
is only one of a variety of clinical conditions observed in Morvan's syndrome cases ranging from confusion and memory loss to hallucination
Hallucination
A hallucination, in the broadest sense of the word, is a perception in the absence of a stimulus. In a stricter sense, hallucinations are defined as perceptions in a conscious and awake state in the absence of external stimuli which have qualities of real perception, in that they are vivid,...
s and delusion
Delusion
A delusion is a false belief held with absolute conviction despite superior evidence. Unlike hallucinations, delusions are always pathological...
s. However, this is a separate disorder.
Also, some studies have linked NMT with certain types of cancers, mostly lung and thymus, suggesting that NMT may be paraneoplastic in some cases. In these cases the underlying cancer will determine prognosis. However, most cases of NMT are autoimmune and not associated with cancer.