63-year-old black man, working in construction, presented with three-decade- history of intermittent muscle cramps. Cramps initially were only triggered by strenuous physical activity under heat and resolved after few minutes of rest, especially with cool temperature. Cramps affected his calves, quadriceps, and arm muscles. Symptoms started to deteriorate in the last two decades, when cramps started occurring spontaneously, more frequently and associated with elevation in creatinine kinase between 4000 and 12,000 IU/L, requiring hospitalization 3–4 times per month. At one time his creatinine kinase (CK) increased up to 26,171 IU/L with severe muscle cramps and pain. He also developed fasciculations in his limbs, abdomen, and back muscles; and atrophy of the right leg muscles below the knee. At the age of 40, when his cramps worsened, he developed progressive ataxia, dysmetria, dysarthria, dysphagia, and problems with reading. At the age of 58, he became wheelchair-bound and developed cognitive problems and bradyphrenia. He suffered from atrial fibrillation, deep venous thrombosis, diabetes, hypertension, and chronic untreated asymptomatic hepatitis C with normal liver function caused by IV drug abuse in his teen years. His medications were insulin, dabigatran, diltiazem, lamotrigine, omeprazole, sotalol, riboflavin, and most recently riluzole for ataxia. His grandmother, mother, and sister suffered from ataxia and painful incapacitating cramps that required multiple hospitalizations. General examination was unremarkable. Neurological examination showed slow horizontal and vertical saccades, dysarthria, bilateral dysmetria, dysdiadochokinesia, severe ataxia, right leg atrophy and generalized areflexia. He displayed a cerebellar deafferentation syndrome with executive dysfunction. Brain MRI showed pan-cerebellar atrophy (Figs. 1A and 1B). Laboratory tests including metabolic panel, vitamin levels, endocrine panel and toxins were negative. Mayo paraneoplastic panel, HIV, ANA, Sjogren panel, ceruloplasmin, Whipple’s polymerase chain reaction (PCR), myositis panel, angiotensin converting enzyme (ACE), anti-cyclic citrullinated peptide (anti-CCP), antiphospholipid and anticardiolipin antibodies, C-reactive protein (CRP), sed rate (ESR), and urine drug screen were all negative. Nerve conduction studies and electromyography (EMG) showed sensory-motor axonal loss polyneuropathy and non-specific myopathic features. The spinocerebellar ataxia type 1 (SCA1) and spinocerebellar ataxia type 3 (SCA3) DNA test, Mayo Clinic paraneoplastic panel, and glutamic acid decarboxylase (GAD 65) were all negative. The SCA2 DNA test showed 39 CAG repeats in the ataxin-2 gene (ATXN2 gene). A right quadriceps muscle biopsy at age 54 showed chronic neurogenic atrophy and no associated inflammation (Figs. 2A and 2B). Muscle biopsy was otherwise negative for inflammatory myopathies, vasculitis, muscular dystrophies, glycogenosis, lipid storage disease, and mitochondrial myopathies.
He failed the following preventive medications for painful muscle cramps and rhabdomyolysis: quinine, gabapentin, clonazepam, diazepam, creatinine, and vitamin B. Pregabalin at 150 mg twice daily remitted all his cramps and rhabdomyolysis attacks for more than four years. His CK values between attacks remained between 400 s and low 1,000 s,