3.5.R3 Recommendation
Pharmacological interventions
- Strength of recommendation:
- Conditional against intervention
- Level of evidence:
- Very low
How the strength and level of evidence are graded
What the strength of a recommendation means
The strength of a recommendation reflects the extent to which a guideline panel is confident that desirable effects of an intervention outweigh undesirable effects, or vice versa, across the range of patients for whom the recommendation is intended.
Strong for (↑↑) or against (↓↓) intervention
For patients: Most individuals in this situation would want the recommended course of action and only a small proportion would not.
For clinicians: Most individuals should receive the recommended course of action.
Conditional for (↑) or against (↓) intervention
For patients: The majority of individuals in this situation would want the suggested course of action, but many would not.
For clinicians: Recognize that different choices will be appropriate for different patients, and that you must help each patient arrive at a management decision consistent with her or his values and preferences.
Neither intervention nor comparison (—)
The panel did not recommend for or against the intervention.
Source: GRADE Handbook, section 6.1, Table 6.1 (GRADE uses “weak” and “conditional” interchangeably).
For the rating of the strength of the recommendation, in addition to evidence from studies in FRDA, evidence from like conditions, clinical experience and expert consensus are taken into account when published evidence is not available.
The level of evidence is based on published evidence from studies in FRDA. If there is no published evidence in FRDA, evidence from other like conditions or clinical expertise may have been used to make the recommendation – this is graded as ‘very low’ or in some cases ‘low’ level evidence. See the table below for an explanation of the symbols used to grade recommendations.
| Strength of recommendation | Symbol | Level of evidence | Symbol |
| Strong for intervention | ↑↑ | High | ⨁⨁⨁⨁ |
| Conditional for intervention | ↑ | Moderate | ⨁⨁⨁◯ |
| Neither intervention nor comparison | — | Low | ⨁⨁◯◯ |
| Conditional against intervention | ↓ | Very low | ⨁◯◯◯ |
| Strong against intervention | ↓↓ |
For people with Friedreich ataxia, we suggest that pharmaceutical therapies are not used to treat dysarthria.
Question
Should pharmaceutical intervention versus no pharmaceutical intervention be used for all people with Friedreich ataxia?
Justification
Very few published studies have used speech as an outcome measure in pharmaceutical trials for Friedreich ataxia. There is very low evidence supporting the use of any pharmaceutical therapies to improve dysarthria in Friedreich ataxia. One open label trial showed minor changes in acoustic outcomes related to timing in the high dose group (versus low dose group) (22). These findings were not verified against listener-based judgements.
Subgroup consideration
This recommendation is for individuals with Friedreich ataxia with dysarthria.
Evidence to recommendation table (PDF)
Part of 3.5 Dysarthria in Friedreich ataxia
References (22)
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2. Hiller F. A study of speech disorders in friedreich's ataxia. Arch Neurol Psychiatry. 1929;22(1):75-90.
3. Corben LA, Klopper F, Stagnitti M, Georgiou-Karistianis N, Bradshaw JL, Rance G, et al. Measuring inhibition and cognitive flexibility in Friedreich ataxia. Cerebellum. 2017;16(4):757-63.
4. Nieto A, Correia R, de Nóbrega E, Montón F, Hess S, Barroso J. Cognition in friedreich ataxia. Cerebellum. 2012;11(4):834-44.
5. Koohi N, Thomas-Black G, Giunti P, Bamiou DE. Auditory phenotypic variability in Friedreich's ataxia patients. Cerebellum. 2021;20(4):497-508.
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8. Hocking DR, Fielding J, Corben L A, Cremer P, Millist L, White O, et al. Ocular motor fixation deficits in Friedreich ataxia. Cerebellum. 2010;9:411-8.
9. Naeije G, Rovai A, Pandolfo M, De Tiege X. Hand dexterity and pyramidal dysfunction in Friedreich ataxia, a finger tapping study. Mov Disord Clin Pract. 2021;8(1):85-91.
10. Poole ML, Wee JS, Folker JE, Corben LA, Delatycki MB, Vogel AP. Nasality in Friedreich ataxia. Clin Linguist Phon. 2015;29(1):46-58.
11. Vogel AP, Wardrop MI, Folker JE, Synofzik M, Corben LA, Delatycki MB, et al. Voice in Friedreich ataxia. J Voice. 2017;31(2):243 e9- e19.
12. Folker J, Murdoch B, Cahill L, Delatycki M, Corben L, A. V. Dysarthria in Friedreich's Ataxia: a perceptual analysis. Folia Phoniatr Logop. 2010;62:97-103.
13. Brendel B, Synofzik M, Ackermann H, Lindig T, Scholderle T, Schols L, et al. Comparing speech characteristics in spinocerebellar ataxias type 3 and type 6 with Friedreich ataxia. J Neurol. 2015;262(1):21-6.
14. Clarke P, Black SE. Quality of life following stroke: Negotiating disability, identity, and resources. J Appl Gerontol. 2005;24(4):319-36.
15. Gibilisco P, Vogel AP. Friedreich ataxia. BMJ. 2013;347:f7062.
16. Parr S, Byng S, Gilpin S. Talking about aphasia: Living with loss of language after stroke. UK: McGraw-Hill Education; 1997.
17. Baylor C, Burns M, Eadie T, Britton D, Yorkston K. A qualitative study of interference with communicative participation across communication disorders in adults. Am J Speech Lang Pathol. 2011;20(4):269-87.
18. Vogel AP, Folker J, Poole ML. Treatment for speech disorder in Friedreich ataxia and other hereditary ataxia syndromes. Cochrane Database Syst Rev. 2014(10):CD008953.
19. Lowit A, Egan A, Hadjivassiliou M. Feasibility and acceptability of Lee Silverman voice treatment in progressive ataxias. Cerebellum. 2020;19(5):701-14.
20. Vogel A, Rommel N, Synofzik M. Intensive speech rehabilitation in degenerative ataxias improves intelligibility (Abstract). Mov Disord. 2018;33(Suppl 2):S281.
21. Vogel AP, Stoll LH, Oettinger A, Rommel N, Kraus EM, Timmann D, et al. Speech treatment improves dysarthria in multisystemic ataxia: a rater-blinded, controlled pilot-study in ARSACS. J Neurol. 2019;266(5):1260-6.
22. Yiu EM, Tai G, Peverill RE, Lee KJ, Croft KD, Mori TA, et al. An open-label trial in Friedreich ataxia suggests clinical benefit with high-dose resveratrol, without effect on frataxin levels. J Neurol. 2015;262(5):1344-53.
Disclaimer, intended use and funding
Disclaimer
The Clinical Management Guidelines for Friedreich ataxia (‘Guidelines’) are protected by copyright owned by the authors who contributed to their development or said authors’ assignees.
These Guidelines are systematically developed evidence statements incorporating data from a comprehensive literature review of the most recent studies available (up to the Guidelines submission date) and reviewed according to the Grading of Recommendations, Assessment Development and Evaluations (GRADE) framework © The Grade Working Group.
Guidelines users must seek out the most recent information that might supersede the diagnostic and treatment recommendations contained within these Guidelines and consider local variations in clinical settings, funding and resources that may impact on the implementation of the recommendations set out in these Guidelines.
The authors of these Guidelines disclaim all liability for the accuracy or completeness of the Guidelines, and disclaim all warranties, express or implied to their incorrect use.
Intended Use
These Guidelines are made available as general information only and do not constitute medical advice. These Guidelines are intended to assist qualified healthcare professionals make informed treatment decisions about the care of individuals with Friedreich ataxia. They are not intended as a sole source of guidance in managing issues related to Friedreich ataxia. Rather, they are designed to assist clinicians by providing an evidence-based framework for decision-making.
These Guidelines are not intended to replace clinical judgment and other approaches to diagnosing and managing problems associated with Friedreich ataxia which may be appropriate in specific circumstances. Ultimately, healthcare professionals must make their own treatment decisions on a case-by-case basis, after consultation with their patients, using their clinical judgment, knowledge and expertise.
Guidelines users must not edit or modify the Guidelines in any way – including removing any branding, acknowledgement, authorship or copyright notice.
Funding
The authors of this document gratefully acknowledge the support of the Friedreich Ataxia Research Alliance (FARA). The views and opinions expressed in the Guidelines are solely those of the authors and do not necessarily reflect the official policy or position of FARA.