Jeremy KCutsforth-Gregory, Senior Associate Consultant Neurologist, Mayo Clinic[email protected]
Elizabeth A. Coon, Rochester, MN
Submitted January 13, 2017
Probstel et al. report a man with a pyramidal, extrapyramidal, and cerebellar syndrome they describe as an "MSA phenotype" [1]. He was ultimately found to have an MT-TL1 gene mutation commonly associated with MELAS. Several clinical and radiographic features are not commensurate with MSA.
Consensus diagnostic criteria for MSA provide three levels of certitude [2]. Definite MSA requires neuropathologic demonstration of CNS alpha-synuclein-positive inclusions. Both probable and possible MSA diagnoses hinge on evidence of autonomic impairment with poorly levodopa-responsive parkinsonism or ataxia [2].
The case in question does not describe orthostatic hypotension, neurogenic bladder, or erectile dysfunction. The slow progression of gait instability over 10 years would be unusual for MSA since the median duration from disease onset to death is 7.5-9.8 years [3, 4, 5]. Similarly, 3 years of clinical stability militates against a diagnosis of MSA, which is inexorably progressive. Radiographically, brain calcifications are not seen in MSA, cerebellar atrophy should be accompanied by pontine atrophy, and cerebellar hypometabolism supports but is not specific for MSA-C.
Progressive parkinsonism and ataxia in an adult should bring to mind MSA, but attention to the consensus diagnostic criteria, especially the core features of autonomic failure, will highlight the possibility of an MSA mimic.
1. Probstel AK, Schaller A, Lieb J, et al. Mitochondrial cytopathy with common MELAS mutation presenting as multiple system atrophy mimic. Neurol Genet 2016;2:e121.
2. Gilman S, Wenning GK, Low PA, et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology 2008;71:670-676.
3. Coon EA, Sletten DM, Suarez MD, et al. Clinical features and autonomic testing predict survival in multiple system atrophy. Brain 2015;138:3623-3631.
4. Low PA, Reich SG, Jankovic J, et al. Natural history of multiple system atrophy in the USA: a prospective cohort study. Lancet Neurol 2015;14:710-719.
5. Wenning GK, Geser F, Krismer F, et al. The natural history of multiple system atrophy: a prospective European cohort study. Lancet Neurol 2013;12:264-274.
Consensus diagnostic criteria for MSA provide three levels of certitude [2]. Definite MSA requires neuropathologic demonstration of CNS alpha-synuclein-positive inclusions. Both probable and possible MSA diagnoses hinge on evidence of autonomic impairment with poorly levodopa-responsive parkinsonism or ataxia [2].
The case in question does not describe orthostatic hypotension, neurogenic bladder, or erectile dysfunction. The slow progression of gait instability over 10 years would be unusual for MSA since the median duration from disease onset to death is 7.5-9.8 years [3, 4, 5]. Similarly, 3 years of clinical stability militates against a diagnosis of MSA, which is inexorably progressive. Radiographically, brain calcifications are not seen in MSA, cerebellar atrophy should be accompanied by pontine atrophy, and cerebellar hypometabolism supports but is not specific for MSA-C.
Progressive parkinsonism and ataxia in an adult should bring to mind MSA, but attention to the consensus diagnostic criteria, especially the core features of autonomic failure, will highlight the possibility of an MSA mimic.
1. Probstel AK, Schaller A, Lieb J, et al. Mitochondrial cytopathy with common MELAS mutation presenting as multiple system atrophy mimic. Neurol Genet 2016;2:e121.
2. Gilman S, Wenning GK, Low PA, et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology 2008;71:670-676.
3. Coon EA, Sletten DM, Suarez MD, et al. Clinical features and autonomic testing predict survival in multiple system atrophy. Brain 2015;138:3623-3631.
4. Low PA, Reich SG, Jankovic J, et al. Natural history of multiple system atrophy in the USA: a prospective cohort study. Lancet Neurol 2015;14:710-719.
5. Wenning GK, Geser F, Krismer F, et al. The natural history of multiple system atrophy: a prospective European cohort study. Lancet Neurol 2013;12:264-274.