Damage in SPG4 extends to nerves of the feet

Measured by lack of sweating response


Damage in SPG4-HSP extends to the peripheral nervous system, especially in the feet, but also in the hands in some cases. This was assessed by an abnormal sweating response.



BACKGROUND AND PURPOSE: SPAST mutations are the most common cause of hereditary spastic paraplegia (SPG4-HSP), which is characterized by progressive lower limb weakness, spasticity and hyperreflexia. There are few studies about non-motor manifestations in this disease and none about autonomic involvement. Therefore, the aim was to determine the frequency and pattern of autonomic complaints in patients with SPG4-HSP, as well as to determine the clinical relevance and the possible factors associated with these manifestations.


METHODS: Thirty-four molecularly confirmed SPG4 patients were recruited in a multicenter cross-sectional study, of whom 26 underwent detailed neurophysiological testing (heart rate variability, sympathetic skin response and the Quantitative Sudomotor Axonal Reflex Test). The Scales for Outcomes in Parkinson’s Disease – Autonomic Questionnaire (SCOPA-AUT) was applied to quantify the severity of autonomic symptoms. Results were compared with 44 age- and gender-matched healthy controls using non-parametric tests. P values <0.05 were considered significant.


RESULTS: In the SPG4-HSP group, there were 18 men with a mean age of 47.7 ± 12.6 years. SCOPA-AUT scores were similar between patients and controls (P = 0.238). Only the urinary domain subscore was significantly higher amongst patients (4 vs. 2.5, P = 0.05). Absent sympathetic skin response in the hands and feet was more frequent amongst patients (20% vs. 0%, P < 0.001, and 64% vs. 0%, P = 0.006, respectively). Quantitative Sudomotor Axonal Reflex Test responses were also smaller throughout all recording regions in the SPG4-HSP group.


CONCLUSION: Our results indicate that SPG4-HSP patients have sudomotor dysfunction caused by damaged small post-ganglionic cholinergic fibers. Damage in SPG4-HSP extends to the peripheral nervous system.


SOURCE: Eur J Neurol. 2018 Nov 29. doi: 10.1111/ene.13878. [Epub ahead of print] PMID: 30489674 © 2018 EAN.


Autonomic dysfunction in hereditary spastic paraplegia type 4


González-Salazar C1, Takazaki KAG1, Martinez ARM1, Pimentel-Silva LR1, Jacinto-Scudeiro LA2,3, Nakagawa ÉY4, Fujiwara Murakami CE4, Saute JAM2,3, Pedroso JL5, Barsottini OGP5, Teive HAG4, França MC Jr1.


1 Department of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil.

2 Medical Genetics and Neurology Services, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.

3 Department of Internal Medicine and Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.

4 Department of Internal Medicine, Neurology Service, Universidade Federal do Paraná, Curitiba, Brazil.

5 Department of Neurology, Federal University of São Paulo (UNIFESP), São Paulo, Brazil.

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