Cramp fasciculation syndrome

Cramp fasciculation syndrome is a rare peripheral nerve hyperexcitability syndrome that is characterized by spontaneous painful muscle cramps and twitches (fasciculations) in otherwise healthy individuals ¹. Cramp fasciculation syndrome can lead to muscle discomfort, pain, tiredness, fatigue, anxiety, hyperreflexia, and paresthesias ². Muscles in the leg are most commonly affected, although cramp fasciculation syndrome may involve several parts of the body. Cramp fasciculation syndrome symptoms are thought to be due to over-activity of the associated nerves.

Although familial cramp fasciculation syndrome cases have been reported, a genetic cause has not yet been identified ². In most cases, cramp-fasciculation syndrome occurs sporadically in people with no family history of the condition.

There is very limited information on the prevalence of cramp-fasciculation syndrome in the US and in the world. Because there are few published cases, many resources generally state that this condition is rare. A Dutch study from 1991 found that 0.4% of men and 0.7% of women experience frequent fasciculations (muscle twitches) and muscle cramps ³.

Cramp-fasciculation syndrome presents with a lower rate of clinical and electrophysiological signs of peripheral nerve hyperexcitability as compared to the more severe member of the same spectrum-neuromyotonia (Isaacs’ syndrome) ⁴. Voltage-gated potassium channel (VGKC)-complex antibodies are often found in a minority of patients with cramp-fasciculation syndrome, but most cases are unexplained. While these antibodies are usually directed against leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) in other peripheral nerve hyperexcitability syndromes, they are mostly against uncharacterized VGKC-complex antigens in cramp-fasciculation syndrome patients ⁵.

There is limited information about the treatment of cramp-fasciculation syndrome, but certain medications have been reported as beneficial in individual cases ⁶, ⁷.

Cramp fasciculation syndrome causes

Cramp-fasciculation syndrome may have multiple underlying causes ⁶. In general, it is thought to be related to abnormal excitability (overactivity) of peripheral neurons.[2] However, in many people with cramp-fasciculation syndrome, the cause cannot be found (idiopathic cramp-fasciculation syndrome) ⁶.

The following have been reported to be associated with cramp-fasciculation syndrome ⁷:

• Genetic or autoimmune dysfunction of ion channels
• Peripheral neuropathy
• Anterior-horn-cell disease
• Metabolic abnormalities
• Tumors (most commonly thymoma)

Some familial cases of cramp-fasciculation syndrome have been reported ⁸. However, at the present time, no genes have been found responsible for familial cases of isolated cramp-fasciculation syndrome (occurring without an associated disorder). Recently, a variant in a gene called TRPA1 was suggested to be responsible for autosomal dominant, carbamazepine-responsive cramp-fasciculation syndrome in a father and son. However, they were thought to have cramp-fasciculation syndrome as part of a more generalized hypersensitivity-hyperexcitability disorder that was causing various additional symptoms ⁸. More research involving a larger number of people with cramp-fasciculation syndrome is needed to identify possible genetic causes of familial and/or isolated cramp-fasciculation syndrome.

Cramp fasciculation syndrome symptoms

Cramp-fasciculation syndrome is primarily associated with spontaneous, painful muscle cramps and muscle twitches (fasciculations), in the absence of an associated underlying diagnosis. Muscles in the legs (thighs and calves) are most commonly affected, although other muscles (such as muscles in the arm or chest) can also be involved. Other signs and symptoms may include burning or prickling sensations (paresthesias), muscle stiffness, over-responsive reflexes (hyperreflexia), anxiety, and fatigue ⁹. Symptoms are often triggered by physical activity and may be relieved by stretching exercises and/or massage. The severity of the condition varies significantly from person to person. In severe cases, cramp-fasciculation syndrome can interfere with daily activities and quality of life ¹⁰.

Cramp fasciculation syndrome diagnosis

A diagnosis of cramp-fasciculation syndrome is generally based on the presence of characteristic symptoms, in otherwise healthy individuals. A history of frequent muscle cramps, twitching, and pain (often worsened by exercise) without muscle weakness or wasting is suggestive of the condition. Some of these symptoms may be more obvious when a person is at rest (i.e. muscle twitching). It is important to rule out other conditions that may cause similar features ⁷.

Electromyography (EMG) or repetitive nerve stimulation studies may also be done to assess the health of muscles and the nerves that control them. In repetitive nerve stimulation studies, muscle responses are recorded when the nerves are repetitively stimulated by small pulses of electricity ¹¹.

Cramp fasciculation syndrome treatment

There is limited information in the medical literature about the treatment of cramp-fasciculation syndrome. Decisions regarding treatment should be carefully considered and discussed with a knowledgeable healthcare provider. Much of what is available describes individual cases. Some people with cramp-fasciculation syndrome improve without treatment.

Meds that help cramp fasciculation syndrome

Treatment with carbamazepine, gabapentin, lamotrigine, or pregabalin (medications that reduce the hyper-excitability of nerves) was described as helpful in improving symptoms in individual cases. Immunosuppressive therapy (e.g., prednisone) has been used to treat cases of cramp-fasciculation syndrome that did not respond to other treatments ⁷.

References

1. Poyraz M, Matur Z, Aysal F, Tüzün E, Hanoğlu L, Öge AE. Clinical, Electrophysiological, and Serological Evaluation of Patients with Cramp-Fasciculation Syndrome. Noro Psikiyatr Ars. 2017;54(2):183-186. doi:10.5152/npa.2016.14816 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5491670
2. Nirenberg MJ, Chaouni R, Biller TM, Gilbert RM, Paisán-Ruiz C. A novel TRPA1 variant is associated with carbamazepine-responsive cramp-fasciculation syndrome. Clin Genet. 2018;93(1):164-168. doi:10.1111/cge.13040 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5654709
3. Jansen PH, van Dijck JA, Verbeek AL, Durian FW, Joosten EM.. Estimation of the frequency of the muscular pain-fasciculation syndrome and the muscular cramp-fasciculation syndrome in the adult population. Eur Arch Psychiatry Clin Neurosci. 1991; 241(2):102-4.
4. Küçükali CI, Kürtüncü M, Akçay Hİ, Tüzün E, Öge AE. Peripheral nerve hyperexcitability syndromes. Rev Neurosci. 2015;26:239–251. https://doi.org/10.1515/revneuro-2014-0066
5. Liewluck T, Klein CJ, Jones LK., Jr Cramp-fasciculation syndrome in patients with and without neural autoantibodies. Muscle Nerve. 2014;49:351–356. https://doi.org/10.1002/mus.23935
6. Shimatani Y, Nodera H, Shibuta Y, Miyazaki Y, Misawa S, Kuwabara S, Kaji R. Abnormal gating of axonal slow potassium current in cramp-fasciculation syndrome. Clin Neurophysiol. June 2015; 126(6):1246-1254. http://www.ncbi.nlm.nih.gov/pubmed/25304174
7. Liewluck T, Klein CJ, Jones LK Jr. Cramp-fasciculation syndrome in patients with and without neural autoantibodies. Muscle Nerve. March 2014; 49(3):351-356. https://www.ncbi.nlm.nih.gov/pubmed/23836298
8. Nirenberg MJ, Chaouni R, Biller TM, Gilbert RM, Paisán-Ruiz C. A novel TRPA1 variant is associated with carbamazepine-responsive cramp-fasciculation syndrome. Clin Genet. April 24, 2017; [Epub ahead of print]:https://www.ncbi.nlm.nih.gov/pubmed/28436534
9. Nirenberg MJ, Chaouni R, Biller TM, Gilbert RM, Paisán-Ruiz C. A novel TRPA1 variant is associated with carbamazepine-responsive cramp-fasciculation syndrome. Clin Genet. January, 2018; 93(1):164-168. https://www.ncbi.nlm.nih.gov/pubmed/28436534
10. Tahmoush AJ, Alonso RJ, Tahmoush GP, Heiman-Patterson TD. Cramp-fasciculation syndrome: a treatable hyperexcitable peripheral nerve disorder. Neurology. July 1991; 41(7):1021-1024. http://www.ncbi.nlm.nih.gov/pubmed/1648679
11. Harrison TB, Benatar M.. Accuracy of repetitive nerve stimulation for diagnosis of the cramp-fasciculation syndrome. Muscle Nerve. June 2007; 35(6):776-780. https://www.ncbi.nlm.nih.gov/pubmed/17405138