Fasciculations occur in association with a variety of neuromuscular diseases. They may occur, however in the presence of no other abnormality. Reed and Kurland observed that spontaneous fasciculations were frequently noted by 70% of normal healthy individuals, particularly those with medical training. The study did not involve long-term follow-up.
We have designed a study to answer two specific questions. Is there a syndrome of benign fasciculations that is different from occasional fasciculations noted by most normal individuals? May these benign fasciculations be an early manifestation of motor neuron disease?

Methods of Study
From the computerized patient registry and the records of the Clinical Neurophysiology Laboratory of the Mayo Clinic, 137 patients were identified (between 1960 and 1988) who met the following criteria: (1) A presenting complaint led to the diagnosis of benign fasciculation. (2) Neurological examination was performed and recorded using the full Mayo neurological examination record by a staff neurologist. This examination was complete and normal. (3) An EMG examination had been completed and showed no evidence of motor neuron disease except for fasciculation potentials. (4)There was a minimum interval of 2 years between the diagnosis and follow-up.

Survey Method
The follow-up survey was a structured telephone interview with open-ended questions. These questions included confirmation of the original information in the patient history and specific questions about the appearance of weakness, family history, persistence of the original symptoms, factors precipitating the original symptoms, and any key factors that exacerbated or relieved existing symptoms.

Results
Of the 137 patients identified, 121 patients were available for follow-up interviews. Two patients had died, 1 of lung cancer and 1 of a self-inflicted gunshot injury. Eight patients declined the formal interview. On brief inquiry, none had developed significant neurological symptoms. Six patients were residents of countries other than the United States and follow-up was not attempted. There were 94 men and 27 women. The mean age at the time of presentation was 42.6 (range 20-72) years for men and women. The mean follow-up interval from time of diagnosis to time of interview was 7.2 (range, 2-32) years. The presenting complaints that led to the diagnose of benign fasciculations are summarized in the Table. Fasciculation was typically identified by the patient as a brief, painless twitch of a part of a muscle. The twitch did not usually produce noticeable joint movement.

Presenting Symptom, Number of Patients

Muscle twitching or fasciculation, 102
Generalized fatigue, 56
Cramps or muscle spasms, 52
Migrating paresthesiae, 51
Generalized muscle aches, 41
Concern about ALS, 17
Muscle stiffness, 17

"The total is greater than 121 because THE MAJORITY OF PATIENTS HAD SEVERAL PRIMARY SYMPTOMS."

Follow-up
None of the 121 patients reported any symptoms suggestive of motor neuron disease. Seventeen patients noted persistence of generalized fatigue but not specific weakness. Sixty of the patients indicated that their symptoms including fasciculations had improved, 40 observed no change since the time of their diagnosis, and 5 felt that the fasciculations had become more prominent. Sixteen patients noticed marked fluctuations of their fasciculations on a daily basis. Factors increasing the symptoms included physical exercise, stress, tiredness, and caffeine consumption. The distribution of fasciculations was generalized in 32 patients and restricted in 85 patients. Forty of the patients were nurses, physicians, physical therapists, or other medical professionals.

The general health of most of the individuals remained excellent. Four patients (present age, 55-68 years) had a diagnosis of leukemia, rheumatoid arthritis, prostate cancer, and Sjogrens syndrome. Two male patients had fathers who died of ALS within 2 years of the study participant presenting with benign fasciculations. One female patient had a maternal uncle with a diagnosis of ALS. One female patient's spouse died with ALS 18 months before her symptoms appeared. Four patients had relatives with multiple sclerosis. Three patients reported that they had first-degree relatives with muscle cramps or muscle twitching but nothing to suggest ALS.

In the follow-up interview, we asked patients whether, in retrospect, they could identify an event that triggered their symptoms. Nineteen patients reported an acute infectious illness in the month prior to onset of symptoms. This was typically a viral upper respiratory or gastrointestinal disturbance. A striking but typical example was a 40 year old professor of neurology who developed an acute and severe gastrointestinal illness with fever, vomiting, and diarrhea lasting 48 hours. Three days after the resolution of this illness, he developed profuse generalized fasciculations but no weakness. The fasciculations persisted until the time of the evaluation 3 weeks later. The profuse fasciculations were not visible clinically but were confirmed by EMG in four of five muscles examined. At follow-up 4 years later, the fasciculations persisted but were less noticeable. Function was entirely normal.
Twenty-two patients noted the onset of fasciculations during a period of increased emotional or physical stress. For 5 patients, medications may have contributed to symptoms; 4 were taking a B-agonist for asthma, and 1, thyroxine. In this latter patient, the fasciculations accompanied documented chemical hyperthyroidism and abated when the patient became euthyroid.

Fifty-one patients described migrating parenthesias. These were distinguished from the subjective feeling of fasciculation or twitching. The parenthesias were typically characterized as brief and of limited distribution. Fasciculations were rarely observed by the neurologist, even when the patient reported their presence and they were present via EMG.

EMG Data

All patients had needle EMG examinations that were normal except for the observation of fasciculation. The mean number of muscles examined in each patient was 9.3 (range, 2 - 21). In 82 patients, the EMG noted at least one muscle with excessive fasciculations. The median number of muscles with excessive fasciculations was 2 (range, 1 - 13). Because an occasional fasciculation may be observed in a normal and asymptomatic individual, this judgment of excessive fasciculation was the subjective interpretation of the electromyographer. In all cases this was a fully trained neurologist-electromyographer.

Discussion
A syndrome of benign fasciculation emerges from a study of this group of 121 patients. In the majority of patients, excess fasciculations was demonstrated by EMG, which suggested that the symptom was not simply a heightened awareness of a normal phenomenon. Fifty-two percent of the 48 patients who presented with fasciculation "alone" were working in medical fields. This compared with 15 medical professionals among the other 73 patients. This suggests that awareness of the possible implications of fasciculations make an individual more likely to seek specialized medical advice. A new observation was the acute onset of symptoms after a viral infection. This association was often striking, as in the case described. This raises the question as to whether, in some cases, the syndrome is related to a benign but perhaps persistent viral invasion of anterior horn cells. An alternative hypothesis is that the infection precipitates a very mild acute inflammatory polyradiculopathy with fasciculation as the only manifestation. The occurrence of fleeting sensory symptoms in almost half of the patients suggests that sensory neurons or roots may also be involved in the process. The uniformly benign prognosis was reassuring. All of the patients with normal examinations and EMG studies had a good outlook. In the subgroup of 15 patients with minor EMG abnormalities, the course was also benign. This suggests that if a patient with benign fasciculation has a normal physical examination performed by an experienced neurologist and a normal EMG examination, they can be strongly reassured. There is only one case in the literature of benign fasciculation progressing to become motor neuron disease. This patient had clear cut motor unit potential abnormalities that distinguished him from the patients we have described.

Conclusion
The syndrome of benign fasciculation, often associated with muscle cramps, appears to be a distinct entity. The historical data suggest that it is multifactorial in origin. The important conclusion is that if the physical examination is normal and the EMG studies are normal or do not suggest motor neuron disease, the patient can be reassured of a completely benign prognosis.