Issacs’ Syndrome, also called neuromyotonia is an uncommon condition emanating from hyperexcitability and continuously firing peripheral nerve axons, which result in activation of muscle fibers (Fleisher et al. 2). Issacs’ syndrome is evident through constant twitching and diminishing reflexes. The symptoms of the disorder develop in people when they are between the age of 15 and 60 years. However, majority starts having the signs before 40 years. The conditions have both acquired and hereditary forms. Hyam Isaacs first described the condition as a form of hyperexcitability of the peripheral nerves in 1961 (Saeed, Zana and Rebeen 83). Denny-Brown and Foley in 1948 had accounted for the electrophysiological impact of undulating myokymia (Maddison 225). However, the number of people affected by the condition remains low globally.
Symptoms and Disease Characteristics
In most cases, Isaacs’ syndrome starts showing the symptoms when individuals are between that age of 15 years and 60 years. However, most of the cases of the condition show first signs before individuals reach 40 years. Muscle stiffness is one of the symptoms that the patients suffering from the condition experience. Some of the patients experience the stiffness of muscles at adolescence with some remaining asymptomatic, even when they become adults. Contraction of the affected muscles often persists when the patient is under general anesthesia or sleeping. One of the ways to notice the condition is through continuous ripples under the skin as the muscles move.
The symptoms associated with periphery nerve hyperexcitability develop over weeks or months (Irani and Angela 189). They vary from one individual to another. Symptoms involved in muscle contractions are continuous. In some cases, voluntary muscle movements trigger the symptoms (Maddison 225). One of the scenarios possible from such instances is the inability of letting go for some time after a voluntary grip. However, affected individuals of experience progressive muscle stiffness. In some cases, the symptoms of the condition are severe to the extent of affecting normal functions of the body such as walking. Therefore, changes in the symptoms that people experience greatly vary.
Studies show the presence of genes that could be playing important role in the inheritance of neuromyotonia. There are reported cases of neuromyotonia for people who inherit dominant disorder of ataxia type 1 (Donaldson and Charles 1315). However, in most conditions, the condition resulting from autoantibodies against the voltage-gated potassium channels in the neurons.
Isaacs’ syndrome can affect various parts of the body. Thus, presenting varied symptoms. In most patients, muscle in the limbs and trunk are the most affected. People with affected limbs may have difficulty in walking as their legs become stiff. The muscles in affected regions may also become fatigued due to hyperactivity. In some cases, the symptoms remain limited to cranial muscles. Cases, where laryngeal muscles are affected, can result in speaking and breathing problems. Therefore, the condition present symptoms depending on the nerves in parts of the body affected. Other symptoms such as increased sweating, cramping and delayed muscle relaxations are also common among affected people.
Physiology of Neuromyotonia
The axons are projections of nerve cells and form crucial components in the nervous system. They often transmit signals to muscles, other neurons and glands. Therefore, they are part of response system in the body. The transmission process in the axons relies on the voltage-gated potassium channels, which stimulated by alteration of the electrical membrane potential close to the channels through changes in ion concentrations. The channel comprises of six helices, S1-S6. Their voltage-sensing parts has helices S1-S4 on the channel border while the pore domain has helices S5-S6 at the center (Grizel, Glukhov and Sokolova 10). The differences in activation of the potassium channel determine the duration and rate of firing by the neurons. Changes in the mechanism involved in axon firing are the primary cause of Isaacs’ syndrome.
Autoimmunity forms the basis for the development of Isaacs’ syndrome. The pathogenic antibodies primarily target the volt-gated potassium channel (VGKCs). These antibodies block the functions of the VGKCs leading to continuous firing by the neurons. However, antibodies do not bind directly to VGKC. Recent studies have shown that the pathogenic antibodies act through two proteins. The antigens recognized by these antibodies include LGI1 and CASPR2 that both form complex with VGKC. These proteins are useful in signal transmission through the synapses. Further confirmation of their involvement is evident in the mutation of their genes found in hereditary Epilepsia (Serratrice and Serratrice 32). Dendrotoxin is one of the substances that significantly contributed to the elaboration of the effects of autoimmunity on Isaacs’ Syndrome through similar targets in the nervous system. The venom also causes hyperexcitability by blocking VGKC.
The volt-gated potassium channels play a crucial role in controlling excitability in the nervous system. In the Isaacs’ syndrome, blocking of their functions through autoimmune response cause continuous firing by the neurons thus activating contractions of the muscles. Isaacs’ syndrome may also prolong the duration of action potential resulting in hyperexcitability. According to Isaac, the disorder resulted in persistent electromyographic activity following the proximal nerve blockade that was abnormal (Plantone, Rosaria and Tatiana 70). More than 40% of persons affected with Isaacs’ Syndrome have anti-VGKC antibodies that can be detected. Nonetheless, there are cases of the Isaacs’ syndrome that result from genetics because of mutation of the KCNA1 gene for potassium channel.
Treatment Options
Treatment options for the condition primarily focus on the symptoms. One of the types of medications given to individuals with this disorder is anticonvulsants. Carbamazepine and phenytoin are some of the drugs that reduce the symptoms associated with neuromyotonia. One of the proposed mechanisms action of these anticonvulsants is through blocking the functions of voltage-gated sodium channels. Drugs such as valproate and phenytoin achieve this objective through prolongation of the recovery duration by the channels after activation (Söderpalm 4). They use this mechanism to prevent the nerves from persistent firing. Other proposed mechanisms of actions that these drugs use to block persistent firing by the nerves exist. They are an effective way of relieving the symptoms of Isaacs’ syndrome. Nonetheless, these medications have various side effects that the patient need to consider while using them. Some of the adverse effects include dizziness, nausea and fatigue.
Another treatment option for the patients suffering from Isaacs’ Syndrome is plasma exchange. The treatment provides short-term relief for the patients. It involves drawing whole blood from the body of affected individuals. Blood cells are then separated from the plasma. The cells are returned to the body while the body will replace the plasma. Use of this treatment aims at reducing the amounts of pathogenic antibodies in the body for a short period to relieve the patient of the symptoms. In additions, patients may receive immunosuppressive drugs to help through the process (Jaben and Jeffrey 271). Even though this method offers the possibility of relief, it does not cure the person and there are cases where it is not effective.
There is no cure for this Isaacs’ Syndrome. Therefore, the patients need to manage the symptoms in the most effective way possible. Moreover, being an autoimmune disease makes it hard to find a possible cure for the condition. Thus, patients can only relieve the symptoms through medications and use of other techniques.
Conclusion
The long-term prognosis of Isaacs Syndrome still remains uncertain. However, there is an improvement in understanding of the condition. New data about the condition are causing enhanced ability to manage the disorder using medications. Nonetheless, remission of the symptoms among the patients is common requiring further studies to improve management. However, the condition does not cause further complications and symptoms are manageable. The life expectancy of the patient varies depending on other health complications. People suffering from Isaacs syndrome together with cancer show reduced life expectancy. Most of the patients have long survival periods through the management of the symptoms. Moreover, the procedures involved in treating the patient due to other conditions may also cause their death. Isaacs’ Syndrome is often described as chronic since it lasts for more than three months. The affected individuals will have to deal with the disorder for the rest of their lives. Most of the symptoms that will affect the individual will appear in the early stages of the disease. Thus, the symptoms may persist with no changes.
Works Cited
Donaldson, Ivan M, and Charles D. Marsden. Marsden's Book of Movement Disorders. Oxford: Oxford Univ. Press, 2011. Print.
Fleisher, Jori et al. “Acquired Neuromyotonia Heralding Recurrent Thymoma in Myasthenia Gravis.” JAMA neurology 70.10 (2013): 1311–1314. PMC. Web. 26 Apr. 2018.
Grizel, A. V., G. S. Glukhov, and O. S. Sokolova. “Mechanisms of Activation of Voltage-Gated Potassium Channels.” Acta Naturae 6.4 (2014): 10–26. Print.
Irani, Sarosh R., and Angela Vincent. "Voltage-gated potassium channel–complex autoimmunity and associated clinical syndromes." Handbook of clinical neurology. Vol. 133. Elsevier, 2016. 185-197.
Jaben, Elizabeth A., and Jeffrey L. Winters. "Plasma exchange as a therapeutic option in patients with neurologic symptoms due to antibodies to voltage‐gated potassium channels: A report of five cases and review of the literature." Journal of clinical apheresis 27.5 (2012): 267-273.
Maddison, Paul. "Neuromyotonia." Practical Neurology 2.4 (2002): 225-229.
Plantone, Domenico, Rosaria Renna, and Tatiana Koudriavtseva. "Neurological diseases associated with autoantibodies targeting the voltage-gated potassium channel complex: Immunobiology and clinical characteristics." Neuroimmunol Neuroinflamm 3 (2016): 69-78.
Saeed, Akam A., Zana A. Mohammed, and Rebeen R. Saeed. "Case Report: A 72 Years Old Man with Isaacs’ Syndrome: A Rare Entity with Different Outcomes." World Journal of Neuroscience 6.02 (2016): 82.
Serratrice, G., and Serratrice, J. “Continuous Muscle Activity, Morvan’s Syndrome and Limbic Encephalitis: Ionic or Non Ionic Disorders?” Acta Myologica 30.1 (2011): 32–33. Print.
Söderpalm, Bo. "Anticonvulsants: aspects of their mechanisms of action." European Journal of Pain6.SA (2002): 3-9.
