SPG11 unresponsive to l-dopa treatment

Damage may be more widespread than thought


Unresponsiveness to Levodopa in SPG11 HSP suggests that damage to dopaminergic pathways may be both pre and post synaptic. Levodopa treatment in Parkinson’s disease helps restore dopamine levels in the brain, eases symptoms and prolongs life.



BACKGROUND: Molecular imaging has proven to be a powerful tool to elucidate degenerated paths in a wide variety of neurological diseases and has not been systematically studied in hereditary spastic paraplegias.

OBJECTIVES: To investigate dopaminergic degeneration in a cohort of 22 patients with hereditary spastic paraplegia attributed to SPG11 mutations and evaluate treatment response to l-dopa.

METHODS: Patients and controls underwent single-photon emission computed tomography imaging utilizing 99m Tc-TRODAT-1 tracer. A single-blind trial with 600 mg of l-dopa was performed comparing UPDRS scores.

RESULTS: Reduced dopamine transporter density was universal among patients. Nigral degeneration was symmetrical and correlated with disease duration and motor and cognitive handicap. No statistically significant benefit could be demonstrated with l-dopa intake during the trial.

CONCLUSION: Disruption of presynaptic dopaminergic pathways is a widespread phenomenon in patients with SPG11 mutations, even in the absence of parkinsonism. Unresponsiveness to treatment could be related to postsynaptic damage that needs to be further investigated.


SOURCE: Mov Disord. 2018 Oct;33(10):1650-1656. doi: 10.1002/mds.27491. Epub 2018 Oct 10. PMID: 30306626 © 2018 International Parkinson and Movement Disorder Society.

SPG11-related parkinsonism: Clinical profile, molecular imaging and l-dopa response.

Faber I1, Martinez ARM1, Martins CR Jr1, Maia ML2, Souza JP2, Lourenço CM3, Marques W Jr3, Montecchiani C4, Orlacchio A4,5, Pedroso JL6, Barsottini OGP6, Ramos CD2, Lopes-Cendes Í7, Friedman JH8, Amorim BJ2, França MC Jr1. 

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

2 Division of Nuclear Medicine, Department of Radiology, University of Campinas (UNICAMP), Campinas, Brazil.

3 Department of Neurology, University of São Paulo (USP-RP), Ribeirão Preto, Brazil.

4 Laboratorio di Neurogenetica, Centro Europeo di Ricerca sul Cervello (CERC)-Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Lucia, Rome, Italy.

5 Dipartimento di Scienze Chirurgiche e Biomediche, Università di Perugia, Perugia, Italy.

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

7 Department of Medical Genetics, University of Campinas (UNICAMP), Campinas, Brazil.

8 Department of Neurology, Butler Hospital and Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA.



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