Analysis of Creatine Kinase Activity in 504 Patients with Proximal Spinal Muscular Atrophy Types I–III from the Point of View of Progression and Severity

Abstract

Mild to moderately elevated creatine kinase (CK) activity is a frequent biochemical finding in proximal spinal muscular atrophy (SMA). In a collaborative study on all types of childhood and juvenile onset SMA, we analysed the CK activity of 504 SMA patients (138 type I, 127 type II, 144 type IIIa, and 95 type IIIb patients). Under the assumption of a lognormal distribution of CK activity as the most appropriate statistical model, CK levels were transformed into logarithms and compared by standard deviation scores = CK-SDS (log). CK activity was statistically different between early and later onset SMA: in SMA I and II, about one-third of patients showed CK-SDS (log) >2 SD, the analysis of the means did not show significant differences. In SMA III, CK-SDS (log) was significantly higher (p < 0.01) than in the two other groups, which was most pronounced in SMA IIIb. More than 90% of SMA IIIb patients showed CK-SDS (log) values >2 vs. 57% in SMA IIIa. As similar values were obtained for a subgroup of 100 patients in whom the diagnosis of autosomal recessive SMA was confirmed by a deletion of the telomeric copy of the survival motor neuron gene, our results can be considered representative for SMA I–III. There was no correlation between CK level and disease duration. The fact that patients were ambulatory or chair-bound had no influence on CK activity in type III SMA. There was no sex influence in SMA I, II and IIIa. The observed higher male values in the group SMA IIIb are most likely the result of a lack of female patients with onset after puberty.

Histopathologically Proven Poliomyelitis with Quadriplegia and Loss of Brainstem Function Due to West Nile Virus Infection

“…During that outbreak, immunohistochemical staining revealed no viral antigen except in samples of neurons, neuronal processes, and areas of necrosis in the gray matter [14]. Motor neuron disease, including acute poliomyelitis, and acute axonal neuropathies can be associated with mild-to-moderate elevations of CK levels [16][17][18][19][20].…”

Observational study of spinal muscular atrophy type I and implications for clinical trials

“…The elevated alanine aminotransferase findings may reflect muscle atrophy (creatine kinase levels were not evaluated here, but have been reported to be elevated in SMA 19 ). Reduced serum bicarbonate may reflect an underlying metabolic acidosis, as has been described previously.…”

Serum creatine kinase levels in spinobulbar muscular atrophy and amyotrophic lateral sclerosis

“…In one study, CK elevation was found in 40% of postpolio patients with neurological symptoms 21. CK elevation also occurs in proximal spinal muscular atrophy (SMA III) 16, 22. In one large study, about 70% of patients with proximal SMA III had elevated CK levels 16…”