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The Incidence and Evolution of Parkinsonian Rigidity in Rett Syndrome: A Pilot Study

  • Peter Humphreys (a1) and Nick Barrowman (a2)

Abstract

Background: Patients with Rett syndrome (RTT) may demonstrate parkinsonian features. Here, we report a preliminary cross-sectional and prospective evaluation of the evolution, regional distribution, and eventual incidence of rigid tone in a cohort of MECP2 mutation-positive patients. Methods: In 51 participants, muscle tone rigidity in extremity regions and neck plus hypomimia were quantified using an RTT rigidity distribution (RTTRD) score with a range of 0 to 15. RTTRD scores were correlated with age, ability to walk and speak, mutation type, and, in a small subgroup (n=9), cerebrospinal fluid (CSF) homovanillic acid (HVA) and 5-hydroxyindole-acetic acid levels. Results: Participant ages ranged from 2 years and 5 months, to 54 years. Rigidity was found in 43/51 (84.3%); it appeared as early as age 3, increased in extent with age, and was present in all participants aged ≥13. Ankle region rigidity appeared first, followed by proximal legs, arms, neck, and face. Ambulatory participants (n=21) had lower RTTRD scores than nonambulatory (n=30; p=0.003). We found a trend to lower scores in participants with retained speech (n=13) versus those with none (n=38; p=0.074), and no difference in scores for those with truncating (n=25) versus missense mutations (n=22; p=0.387). RTTRD scores correlated negatively with CSF HVA levels (R=−0.83; p=0.005), but not with 5-hydroxyindole-acetic acid levels (R=−0.45; p=0.22). Conclusions: Although assessment of muscle tone is somewhat subjective and the RTTRD has not been validated, this study nevertheless suggests that parkinsonian rigidity in RTT is common and frequently increases in extent with age; its severity correlates directly with impaired ambulation and inversely with CSF HVA levels.

Étude pilote portant sur l’incidence et l’évolution de la rigidité parkinsonienne dans le cas du syndrome de Rett. Contexte: Des patients atteints du syndrome de Rett sont susceptibles de manifester des caractéristiques cliniques parkinsoniennes. Nous voulons ici rendre compte d’une évaluation préliminaire transversale et prospective de l’évolution, de la distribution régionale et de l’incidence éventuelle de la rigidité au sein d’une cohorte de patients porteurs de la mutation du gène MECP2. Méthodes: La rigidité musculaire des extrémités du corps, du cou ainsi que l’hypomimie ont été quantifiées chez 51 participants au moyen d’une distribution de la rigidité associée au syndrome de Rett, les scores variant de 0 à 15. Ces derniers ont ensuite été corrélés avec des variables telles que l’âge, la capacité de marcher et de parler, le type de mutation et, dans le cas d’un sous-groupe (n = 9), les quantités d’acide vanillique et d’acide 5-hydroxyindolacétique dans le liquide cérébro-spinal (LCS). Résultats: L’âge des participants variait de 2 ans et 5 mois à 54 ans. Des signes de rigidité ont été observés chez 43 participants sur 51, soit 84,3 %. Ils sont apparus dès l’âge de 3 ans, se sont accrus au fil des années et étaient observables chez tous les participants âgés de 13 ans et plus. Ces signes sont apparus initialement dans la région de la cheville ; ont suivi les portions proximales des jambes, les bras, le cou et le visage. Les participants ambulatoires (n = 21) ont obtenu de plus faibles scores de distribution de la rigidité associée au syndrome de Rett que les patients non-ambulatoires (n = 30; p = 0,003). Nous avons aussi observé de plus faibles scores chez les participants atteints de blocage de la parole (n = 13) par rapport à ceux n’étant pas atteints (n = 38; p = 0,074). Aucune différence dans les scores n’est apparue chez ceux dont les mutations entraînent la synthèse d’une protéine tronquée (n = 25) comparativement à ceux affectés par une mutation faux sens (n = 22; p = 0,387). De plus, les scores de distribution de la rigidité associée au syndrome de Rett ont été corrélés négativement avec des quantités d’acide vanillique dans le LCS (R = -0,83; p = 0,005), mais pas avec des quantités d’acide 5-hydroxyindolacétique (R = - 0,45; p = 0,22). Conclusions: Bien que l’évaluation de la tonicité musculaire demeure quelque peu subjective et que la distribution de la rigidité associée au syndrome de Rett n’ait pas été validée, cette étude suggère néanmoins qu’une telle rigidité est répandue et que sa sévérité augmente fréquemment avec les années. Cette sévérité est directement corrélée avec des troubles de l’ambulation et indirectement corrélée avec des quantités d’acide vanillique dans le LCS.

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Copyright

Corresponding author

Correspondence to: Peter Humphreys, 401 Smyth Road, Ottawa, ON, K1H8L1 Canada. Email: phumphreys@cheo.on.ca

Footnotes

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A portion of this work was presented at the annual meeting of the Canadian Neurosciences Federation in Quebec City, June, 2010.

Footnotes

References

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