Difficulty telling HSP and PLS apart

Diagnostic test could help


Dr. Steve Vucic
Dr. Steve Vucic

Neurologists sometimes struggle to definitively tell the difference between HSP and PLS, leaving patients with the uncertainty and possibility that their condition could be either one, and it could remain unresolved for years.

Neurogeneticist Dr. Carolyn Sue
Neurogeneticist Dr. Carolyn Sue

Australian researchers, including Steve Vucic of Westmead and Carolyn Sue, who is part of the HSP research team that receives funding support from this Foundation, found that cortical dysfunction could help differentiate HSP from PLS. By testing cortical excitability it was found to be normal in HSP, while cortical inexcitability predominates in PLS and cortical excitability in ALS.



Cortical hyperexcitability has been identified as an important pathogenic mechanism in motor neuron disease (MND). The issue as to whether cortical hyperexcitability is a common process across the MND phenotypes, including amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS), remains unresolved.

Separately, the clinical distinction between PLS and ‘mimic disorders’ such as hereditary spastic paraparesis (HSP) may be difficult, potentially delaying diagnosis. Consequently, the aim of the present study was to determine the nature and spectrum of cortical excitability changes across the MND phenotypes, and to determine whether the presence of cortical dysfunction distinguishes PLS from HSP.



Cortical excitability studies were undertaken on a cohort of 14 PLS, 82 ALS and 13 HSP patients with mutations in the spastin gene.



Cortical hyperexcitability, as heralded by reduction of short interval intracortical inhibition (PLS 0.26%, -3.8% to 1.4%; ALS -0.15%, -3.6% to 7.0%; P < 0.01) and cortical silent period duration (CSPPLS 172.2 ± 5.4 ms; CSPALS 178.1 ± 5.1 ms; P < 0.001), along with an increase in intracortical facilitation was evident in ALS and PLS phenotypes, although appeared more frequently in ALS. Inexcitability of the motor cortex was more frequent in PLS (PLS 71%, ALS 24%, P < 0.0001). Cortical excitability was preserved in HSP.



Cortical dysfunction appears to be an intrinsic process across the MND phenotypes, with cortical inexcitability predominating in PLS and cortical hyperexcitability predominating in ALS. Importantly, cortical excitability was preserved in HSP, thereby suggesting that the presence of cortical dysfunction could help differentiate PLS from HSP in a clinical setting.


SOURCE: Eur J Neurol. 2015 May;22(5):826-e58. doi: 10.1111/ene.12669. Epub 2015 Feb 12. © 2015 EAN. PMID: 25683471 [PubMed – in process]


Cortical excitability changes distinguish the motor neuron disease phenotypes from hereditary spastic paraplegia.


Geevasinga N1, Menon PSue CMKumar KRNg KYiannikas CKiernan MCVucic S.

1 Westmead Clinical School, University of Sydney, Sydney, NSW, Australia.


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