A Woman With Muscle Cramps and Fasciculations

A 53-year-old woman complained of frequent muscle spasms, cramps, and mild fluctuating weakness in the arms and legs for 6 years. She initially had difficulty rising from a squat position and had pharynx and tongue spasms that occasionally caused dysphagia. Her symptoms improved recently with celecoxib and clonazepam. She denied difficulty breathing or constipation.

Past medical history was unremarkable. She had three healthy children. Her father was diagnosed with amyotrophic lateral sclerosis (ALS) and died after an 18-year history of progressive weakness, but there are no details of his clinical presentation. One sister had a history of muscle cramps, spasms, and an elevated serum creatine kinase (CK). Another sister had epilepsy and one died of leukemia. She also had three healthy siblings.

Examination revealed normal mentation and cranial nerves. There was no tongue atrophy or fasciculations, and the palate was intact ( Fig. 106-1 ). She had mild hip extensor weakness, and mild hand tremor and fasciculations were seen after muscle activity, but there was no myotonia. Sensation was normal except for mildly decreased vibration sense in the toes. Gait was normal. There were no Babinski signs. The rest of the examination was normal.

Laboratory studies revealed a normal complete blood count, comprehensive metabolic panel, thyroxine and thyroid-stimulating hormone, alanine transaminase, aspartate aminotransferase, and l -lactate dehydrogenase. Serum immunoelectrophoresis was normal except for an IgG of 1840 mg/dL (normal, 700–1600 mg/dL); there were normal GM1 ganglioside antibodies and hexosaminidase A. Serum CK was 520 IU/L (normal, 60–218 IU/L). Spinal fluid was normal with a protein level of 31 mg/dL.

What is the Differential Diagnosis?

Fasciculations are frequently seen in normal people, although in some these might be more frequent, and these individuals are considered to have a syndrome of benign fasciculations . When cramping is more severe, this is called the cramp fasciculation syndrome . These can be disabling and may be associated with mildly elevated CK.

Muscle fasciculations can also be seen in various neurologic conditions, including particularly some neuropathies, like multifocal motor neuropathy, and motor neuron diseases, such as ALS, Kennedy syndrome, and spinal muscular atrophy (SMA). These can be occasionally seen focally in radiculopathies, and also occur in debranching enzyme deficiency.

The family history of her father having “slowly progressive ALS” and one sister with cramps and elevated CK suggests an autosomal-dominant inheritance and is against the autosomal-recessive chromosome 5–associated SMA of adult onset. An autosomal-dominant SMA has also been reported. Autosomal-dominant ALS, with prominent lower motor neuron signs and slow progression, is another possibility.

An EMG Test was Performed

Motor Nerve Studies

Nerve and Site	Latency (ms)	Amplitude (mV)	Conduction Velocity (m/s)
Peroneal Nerve R.	Normal ≤ 5.7	Normal ≥ 3	Normal ≥ 40
Ankle	3.8	8	–
Fibular head	8.8	6	50
Knee	10.4	6	50

Nerve and Site	Latency (ms)	Amplitude (mV)	Conduction Velocity (m/s)
Tibial Nerve L.	Normal ≤ 5.3	Normal ≥ 4	Normal ≥ 40
Ankle	3.3	19	–
Pop. fossa	10.6	17	48

Nerve and Site	Latency (ms)	Amplitude (mV)	Conduction Velocity (m/s)
Median Nerve R.	Normal ≤ 4.2	Normal ≥ 6	Normal ≥ 50
Wrist	4.5	14	–
Elbow	7.8	14	58

Ulnar Nerve R.	Normal ≤ 3.6	Normal ≥ 8	Normal ≥ 50
Wrist	2.6	11	–
Below elbow	5.6	11	58
Above elbow	7.5	11	64

F-Wave and Tibial H-Reflex Studies

Nerve	Latency (ms)	Normal Latency ≤ (ms)
Peroneal nerve R.	40.5	54
Tibial nerve L.	45.0	54
Median nerve R.	24.3	30
Ulnar nerve R.	24.6	30
H-reflex R.	33.6	34
H-reflex L.	33.8	34

Sensory Nerve Studies

Nerve	Onset Latency (ms)	Normal Onset Latency ≤ (ms)	Peak Latency (ms)	Normal Peak Latency ≤ (ms)	Amp (μV)	Normal Amp ≥ (μV)	Conduction Velocity (m/s)	Normal Conduction Velocity ≥ (m/s)
Sural nerve R.	2.9	3.5	3.4	4.0	14	11	48	40
Superficial peroneal nerve R.	3.0	3.5	3.5	4.0	5	8–10	46	40
Sural nerve L.	2.8	3.5	3.3	4.0	5	11	50	40
Median nerve R.	2.6	2.6	3.1	3.1	11	20	50	50
Ulnar nerve R.	2.1	2.6	2.6	3.1	3	13	57	50
Radial nerve R.	2.0	2.6	2.5	3.1	11	30	50	50