A Man With Muscle Spasms and Elevated Serum Creatine Kinase

A 46-year-old, right-handed man presented with mild lower-extremity weakness of a year’s duration. He is a house painter who developed low back and neck pain with progressive upper-extremity weakness after a fall at work about 3 months prior to our evaluation. He had progressive difficulty walking with falls at least once a day. He also had some numbness in all four extremities for about a year. He had no bulbar dysfunction or sphincter disturbances but had cramps and muscle spasms in all four extremities since early childhood. He also had a history of muscles “twitching.” His family history was negative for neurologic illnesses. He had one healthy daughter.

The initial workup included normal complete blood count and routine chemistry profile including electrolytes, glucose, blood urea nitrogen creatinine, calcium, and phosphorus. Serum creatine kinase (CK) was elevated at 2573 IU/L (normal, 30–220 IU/L), lactate dehydrogenase 873 IU/L (normal, 0–250 IU/L), and aspartate transaminase 68 IU/L (normal, 0–40 IU/L). Erythrocyte sedimentation rate, serum protein electrophoresis, fluorescent antinuclear antibody, rheumatoid factor, thyroid function tests, B ₁₂ /folate, urine heavy metal screen, GM ₁ ganglioside antibodies, and cerebrospinal fluid were normal/negative. An MRI of the cervical spine was normal.

The patient received a trial of gamma globulin infusions without benefit and was referred to us.

General physical examination was normal, and he had no organomegaly, gynecomastia, or testicular atrophy. He had normal mentation, and the cranial nerves were normal except for perioral fasciculations. No tongue atrophy or weakness was noted. He had moderate proximal weakness in all four extremities and bilateral hand weakness and mild interossei muscle wasting ( Fig. 36-1 ). There was areflexia in all four limbs with diffuse scattered fasciculations. No Babinski signs were elicited. He had hypoesthesia to pinprick with diminished vibration sense in the hands and feet. Position sense was intact. Gait was somewhat slow and waddling, but it was not ataxic. The rest of the examination was normal.

What is the Differential Diagnosis?

The diffuse weakness and fasciculations are suggestive of a motor neuron disease, but the lack of bulbar symptoms and long tract signs is against the diagnosis of amyotrophic lateral sclerosis (ALS). A lower motor neuron syndrome such as progressive spinal muscular atrophy and familial spinal muscular atrophy should be considered, particularly as the patient has had cramps since childhood. A craniocervical junction disease or a cervical spondylosis is also a possibility, particularly because of the history of neck pain, but the distal sensory findings and fasciculations in the face are against these diagnoses, which were ruled out by the normal MRI.

The sensory complaints and findings with areflexia could also suggest a peripheral neuropathy such as chronic inflammatory demyelinating polyradiculoneuropathy, but fasciculations are not typical for this disease, particularly when present in the face. Limb fasciculations could be seen in multifocal motor neuropathy and sometimes in multifocal motor sensory neuropathy, or Lewis–Sumner syndrome, but they do not occur in the face. The sensory complaints would favor the latter, but in those, the presentation is more asymmetric and multifocal. A hereditary polyneuropathy, such as Charcot–Marie–Tooth disease, is unlikely, due to the lack of a family history or high arches, the presence of facial fasciculations, and proximal weakness.

The lack of family history, bulbar signs, gynecomastia, or testicular atrophy are somewhat against the diagnosis of bulbospinal atrophy or Kennedy’s disease, a condition in which there could be evidence of a mild sensory neuropathy and facial fasciculations; about 50% of these patients have an elevated CK as in this case.

The elevation of CK could also suggest a myopathy, but the fasciculations and sensory findings make that diagnosis unlikely. Elevated CK can also occur in motor neuron disorders such as ALS and spinal muscular atrophy.