Acquired Neuromyotonia causes stiffness and twitching in muscles due to continuous motor unit activity. Neuromyotonia treatment includes anticonvulsant drugs.

Acquired Neuromyotonia

PNS SHIFA

Online Consultation

Syed Intisar Hussain

Overview

<p>Acquired neuromyotonia (AN) or Isaac&#39;s syndrome is a rare immune disorder that results in hyperexcitability of the peripheral motor nerves<sup><a href="#accordion">[1][2]</a></sup>. First described by Hyam Isaacs in the 1960s, this disorder presents as cramps, twitching, myokymia or ocular myotonia (eyelid twitching), pseudomyotonia (delayed or abnormally slow relaxation in muscle contraction after a voluntary movement), or fasciculations of the muscles<sup><a href="#accordion">[1]</a></sup>.</p>

<p>Acquired neuromyotonia affects the muscles of the limb and trunk<sup><a href="#accordion">[1]</a></sup>;&nbsp;muscles of the hand and feet are typically affected in this disorder<sup><a href="#accordion">[2]</a></sup>. Muscle cramps and stiffness are the most prominent features of this disorder and they are often accompanied by increased sweating (hyperhidrosis) and weight loss<sup><a href="#accordion">[3]</a></sup>.&nbsp;</p>

<p>There may be intermittent speech difficulties<sup><a href="#accordion">[1]</a></sup>. Moreover, symptoms of acquired myotonia may persist even when the affected individual is sleeping or is under general anesthesia<sup><a href="#accordion">[2]</a></sup>.&nbsp;Acquired neuromyotonia is diagnosed based on clinical features that are characteristic of this disorder along with electromyography (EMG) studies<sup><a href="#accordion">[3]</a></sup>.</p>

<div>&nbsp;</div>

<p>Acquired neuromyotonia or Isaac&#39;s syndrome is an extremely rare disorder that affects muscle functioning. It is estimated that nearly 100-200 people worldwide are affected by this condition<sup><a href="#accordion">[4][5]</a></sup>.</p>

<p>This disorder affects both males and females. However, it is slightly more common in males. The disease is mostly seen in individuals between the ages of 15 and 60 years; in some cases, the disease has also been reported in childhood<sup><a href="#accordion">[2]</a></sup>.</p>

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Signs And Symptoms

<p>Acquired Neuromyotonia or Isaac&#39;s syndrome or Isaacs-Merten syndrome presents with a myriad of clinical features. The symptoms of this disorder persist even during sleep.&nbsp;</p>

<p>&nbsp;</p>

<p>Acquired myotonia symptoms and signs include<sup><a href="#accordion">[4][6]</a></sup>:</p>

<ul>
	<li>Progressive stiffening of muscle&nbsp;</li>
	<li>Difficulty in muscle coordination (ataxia)</li>
	<li>Changes in heart rate</li>
	<li>Continuous contraction and twitching of the muscle&nbsp;</li>
	<li>Fatigue</li>
	<li>Insomnia&nbsp;</li>
	<li>Muscle cramps&nbsp;</li>
	<li>Excessive sweating (hyperhidrosis)</li>
	<li>Weight loss&nbsp;</li>
	<li>Abnormally slow relaxation of the muscle</li>
	<li>Twitching or quivering of the muscle which is described as sensation of having worms under the skin (myokymia)</li>
	<li>Weak muscle reflexes&nbsp;</li>
	<li>Muscle pain&nbsp;</li>
	<li>Difficulty while speaking or breathing, i.e. activities involving laryngeal muscles or muscle of the throat</li>
</ul>

<div>&nbsp;</div>

Causes

<p>The exact cause linked with acquired neuromyotonia is not known since it&#39;s an immune mediated condition in which the body&#39;s immune system starts attacking its own cells. However, this condition develops when the immune system forms antibodies against the voltage gated potassium channel (VGKC) that are located at the junction of the nerve fiber and muscle cell<sup><a href="#accordion">[2]</a></sup>. Around 40% of people with this disorder develop antibodies against VGKC.</p>

<p>&nbsp;</p>

<p>Acquired neuromyotonia has an autoimmune basis and it is associated with cancer as 21-25% of individuals who have Isaac&#39;s syndrome develop malignancy. This makes it necessary to screen patients for the development of any recent tumor<sup><a href="#accordion"><span style="font-size:10.8333px">[7]</span></a></sup>.&nbsp;</p>

<p>&nbsp;</p>

Diagnosis

<p>The diagnosis of acquired neuromyotonia is made upon the identification of classical clinical features of the disorder along with confirmation through different investigations<sup><a href="#accordion">[2]</a></sup>.&nbsp;</p>

<p>&nbsp;</p>

<ul>
	<li>
	<h5><strong>Clinical Features&nbsp;</strong></h5>
	</li>
</ul>

<p>The clinical presentation of acquired myotonia includes continuous muscle contraction, particularly in the face and hands, which presents as fasciculations.&nbsp;</p>

<p>&nbsp;</p>

<ul>
	<li>
	<h5><strong>Electromyography (EMG)&nbsp;</strong></h5>
	</li>
</ul>

<p>The diagnosis is then confirmed through EMG studies, which show signs of abnormal muscle contraction that are characteristic of this disorder.</p>

<p>&nbsp;</p>

<ul>
	<li>
	<h5><strong>Serum Investigations&nbsp;</strong></h5>
	</li>
</ul>

<p>This involves testing the blood for the presence of antibodies against VGKC.&nbsp;</p>

<p>&nbsp;</p>

<p>Acquired neuromyotonia is sometimes misdiagnosed as other disorders, such as ripping muscle syndrome, stiff-person syndrome, or cramp-fasciculation syndrome, which have similar clinical presentation<sup><a href="#accordion">[4]</a></sup>.</p>

<div>&nbsp;</div>

Treatment

<p>So far there is no absolute cure available for acquired neuromyotonia. Therefore, treatment aims toward the reduction of symptoms and improving the quality of life.&nbsp;</p>

<p>If acquired neuromyotonia is due to any underlying autoimmune disease or malignancy, then it is recommended to treat the preexisting condition simultaneously while managing its symptoms.&nbsp;</p>

<p>&nbsp;</p>

<ul>
	<li>
	<h5><strong>Anticonvulsants&nbsp;</strong></h5>
	</li>
</ul>

<p>Anticonvulsants or antiseizure medications, which are given to epilepsy patients, are used to relieve the muscular spasms, muscle stiffness, and pain. These drugs include phenytoin and carbamazepine and they have proved to be effective in treating the symptoms<sup><a href="#accordion">[4]</a></sup>.</p>

<p>&nbsp;</p>

<ul>
	<li>
	<h5><strong>Immunosuppressants&nbsp;</strong></h5>
	</li>
</ul>

<p>Since it&rsquo;s an autoimmune condition where the body&#39;s immune cells attack its own tissues, immunosuppressive drugs are another treatment option to treat acquired neuromyotonia. Drugs like methotrexate and azathioprine&nbsp;suppress the immune system<sup><a href="#accordion">[4]</a></sup>.&nbsp;</p>

<p>&nbsp;</p>

<ul>
	<li>
	<h5><strong>Corticosteroids&nbsp;</strong></h5>
	</li>
</ul>

<p>Corticosteroids, such as prednisolone, are given orally to suppress the immune system and alleviate the symptoms of acquired neuromyotonia<sup><a href="#accordion">[4]</a></sup>.&nbsp;</p>

<p>&nbsp;</p>

<ul>
	<li>
	<h5><strong>Plasma Exchange (Plasmapheresis)</strong></h5>
	</li>
</ul>

<p>There are antibodies against the VGKC in acquired neuromyotonia so plasma exchange helps to filter out damaging antibodies from the patient&rsquo;s blood<sup><a href="#accordion">[4]</a></sup>.&nbsp;</p>

<div>&nbsp;</div>

<p>Myasthenia gravis, thymoma, and anti-acetylcholine receptor disorders are some reported complications<sup><a href="#accordion">[8]</a></sup>.&nbsp;</p>

<p>&nbsp;</p>

<p>These include<sup><a href="#accordion">[4][9]</a></sup>:</p>

<ul>
	<li>Cancer&nbsp;</li>
	<li>Hashimoto&#39;s thyroiditis&nbsp;</li>
	<li>Myasthenia gravis&nbsp;</li>
	<li>Thymomas</li>
	<li>Vitamin B12 deficiency&nbsp;</li>
	<li>Connective tissue disorders&nbsp;</li>
	<li><a href="https://www.merisehat.pk/disease/celiac-disease" target="_blank">Celiac disease</a></li>
	<li><a href="https://www.merisehat.pk/disease/guillain-barre-syndrome-108" target="_blank">Guillain-Barre syndrome&nbsp;</a></li>
	<li><a href="https://www.merisehat.pk/disease/systemic-lupus-erythematosus" target="_blank">Lupus</a></li>
	<li><a href="https://www.merisehat.pk/disease/rheumatoid-arthritis" target="_blank">Rheumatoid arthritis&nbsp;</a></li>
	<li>Peripheral neuropathy&nbsp;</li>
	<li>Chronic inflammatory demyelinating polyneuropathy&nbsp;</li>
</ul>

<div>&nbsp;</div>

<p>Since the exact cause of the disease isn&#39;t known; therefore, there are currently no strategies that could prevent the disease from developing<sup><a href="#accordion">[4]</a></sup>.</p>

<p>&nbsp;</p>

<p>Clinical features of acquired neuromyotonia mainly focus on the motor aspect of the disease, even though a sensory component was seen in one-third of the patients in a published case series.&nbsp;</p>

<p>Sensory symptoms &ndash; numbness, tingling, or paroxysmal electrical sensation &ndash; were reported as the most prominent complaints. These episodes were usually brief and either involved the acral regions (peripheral part of the body), had a generalized distribution, or were presented in focal regions such as the neck or torso. These sensory symptoms usually occurred spontaneously, but some episodes were triggered by compression, stretching of the nerve, or trauma. However, one patient with sensory symptoms responded well to gabapentin similar to individuals with the classic motor features of acquired neuromyotonia<sup><a href="#accordion">[10]</a></sup>.</p>

<div>&nbsp;</div>

Key Points

<ul>
	<li>Acquired neuromyotonia (also known as Isaac&rsquo;s syndrome, Isaacs-Merten syndrome) is a rare muscular disorder.</li>
	<li>Hyperexcitability of the peripheral motor nerves is observed in individuals with Isaac&rsquo;s syndrome.&nbsp;</li>
	<li>Acquired neuromyotonia symptoms involve muscle cramps, stiffening of the muscles, myokymia, and fasciculations of the muscles.&nbsp;</li>
	<li>This is an extremely rare disease with only 100-200 cases worldwide.</li>
	<li>Diagnosis is based upon clinical features of the disease and electromyography studies.</li>
	<li>Treatment involves antiseizure medications, immunosuppressants, steroids, and plasmapheresis.&nbsp;</li>
</ul>

<div>&nbsp;</div>

[1] Stacey Jankelowitz. Acquired Neuromyotonia. July 2012. Brain Foundation.

[2] Acquired Neuromyotonia - NORD (National Organization for Rare Disorders).

[3] Sukajintanakarn D, Mitrabhakdi E, Phanthumchinda K. Acquired neuromyotonia (Isaacs' syndrome): a case report with autonomic physiologic studies. J Med Assoc Thai. 2006;89(8):1308-1312.

[4] Isaacs’ Syndrome: Causes, Symptoms, Prognosis & Treatment. Cleveland Clinic.

[5] Fang L, Fang L. Living with Issacs’ Syndrome, a Rocky Story — Rare Genomics Institute. Rare Genomics Institute.

[6] Isaacs' Syndrome | National Institute of Neurological Disorders and Stroke.

[7] Park S, Thurbon R, Kiernan M. Isaacs syndrome: the frontier of neurology, psychiatry, immunology and cancer.

[8] Okutani H, Okano Y, Hirose M. Painful myokymia after surgery in a patient with Isaacs’ syndrome: a case report. JA Clin Rep. 2020;6(1). doi:10.1186/s40981-020-00321-y

[9] Isaacs Syndrome - Neurologic Disorders - MSD Manual Professional Edition. MSD Manual Professional Edition.

[10] Herskovitz S, Song H, Cozien D, Scelsa S. Sensory symptoms in acquired neuromyotonia. Neurology. 2005;65(8):1330-1331. doi:10.1212/01.wnl.0000180688.06885.6f

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