Treatment helps symptoms for some SPG11 HSP

Improvement in walking



SPG11 HSPers normally have complicated HSP and some have a unique biochemical imbalance. After treatment with L-Dopa/carbidopa and Sapropterin, correction of the biochemical imbalance and significant gait improvement were found in all 4 participants in this US study who have this unique biochemical imbalance.


Note: this treatment would be expected to be successful only in SPG11 HSPers with this unique biochemical imbalance.


Objective: Report the clinical findings of four patients with HSP due to mutations of SPG11 and a secondary neurotransmitter disorder.

Background Complicated hereditary spastic paraplegias (HSP) associated with thin corpus callosum and cognitive delays may be due to SPG11 (spatacsin or KIAA1840). Previous reports have identified extrapyramidal symptoms in SPG11 patients and improvement with empiric dopaminergic agents.

Design/Methods: Four patients with clinical findings consistent with HSP and with ultimate identification of mutations in KIAA1840 were evaluated as part of the Undiagnosed Disease Program at the NIH or the Myelin Disorders Bioregistry Project according to IRB approved protocols. As part of the evaluation of extrapyramidal symptoms, cerebrospinal fluid (CSF) neurotransmitters were analyzed by standard clinical approaches. Patients were examined before and after initiation of treatment with L-dopa/carbidopa, including comprehensive neurologic examination and timed gait analysis.

Results: Three out of four subjects had decreased levels of homovanillic acid (HVA) and low or borderline tetrahydrobiopterin (BH4) on CSF analysis. One subject also had decreased 5-hydroxyindoleacetic acid (5H1AA). These subjects were all treated symptomatically with L-Dopa/carbidopa and two subjects were treated with Sapropterin. The fourth subject, the brother of one of the above subjects, had normal CSF values of BH4, 5H1AA and HVA but was nevertheless treated with L-Dopa/carbidopa empirically due to symptoms of dystonia and gait freezing. In two subjects, CSF was retested after treatment with normalization of abnormalities. Gait improvement was noted in all subjects (example average of four trials of timed gait analysis in one subject; on: 16.57 + 2.9 sec vs. off: 29.65 + 8.9 sec).

Conclusions: Likely secondary deficits in homovanillic acid (HVA), tetrahydrobiopterin (BH4) and 5-hydroxyindoleacetic acid (5H1AA) may be seen in SPG11. Biochemical normalization and gait improvement can be seen after treatment with L-Dopa/carbidopa and Sapropterin in SPG11.


SOURCE: Neurology April 25, 2012; 78(Meeting Abstracts 1): P05.133 doi: 10.1212/WNL.78.1

Neurotransmitter Abnormalities and Response to L-Dopa in SPG11

Adeline Vanderver1, Davide Tonduti2, Pierre Lebon3, Nenad Blau4, Johanna Loewenstein5, William Gahl6, Camilo Toro7 and Keith Hyland8


1 Childrens National Medical Center Washington DC 
2 IRCCS C. Mondino Institute of Neurology Foundation Pavia Italy
3 Hopital Cochin Paris universite Paris Descartes Paris France
4 Zurich ZH Switzerland
5 Children’s National Medical Center Washington DC 
6 NHGRI, NIH Bethesda MD 
7 NINDS, NIH Frederick MD 
8 Atlanta GA United States


    1. Editor’s Note: You will need to consult your children’s neurologist about whether the particular type of SPG11 that they have is treatable. If it is not, then management and treatment of the symptoms is all that is available.

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