Neurological, cardiological, and oculomotor progression in 104 patients with Friedreich ataxia during long-term follow-up.
BACKGROUND
Friedreich ataxia (FA) is the most frequent autosomal recessive cerebellar ataxia. Although the phenotype is well known, disease progression has not been evaluated in a prospective manner.


OBJECTIVE
To perform a long-term prospective follow-up of neurological, cardiological, and oculomotor function in patients with FA (FA patients).


METHODS
In this open-labeled prospective survey, we examined 104 FA patients every 6 months during a median period of 5 years (range, 6 months to 7 years), with a systematic standardized protocol. Data are reported as mean +/- SD.


METHODS
Neurological examinations were performed at the Federation of Neurology and the Department of Genetics of the Salpêtrière Hospital, Paris, France. Cardiological follow-up was performed at the Department of Cardiology; oculomotor examinations were performed at the Institut National de la Santé et de la Récherche Médicale Unit 679, at the same hospital. Patients We studied 104 FA patients with a confirmed molecular diagnosis. None were receiving antioxidant therapy at baseline; 88 accepted treatment with the coenzyme Q(10) analogue idebenone (5 mg/kg per day). Sixteen preferred not to be treated.


METHODS
Neurological status was evaluated with the International Cooperative Ataxia Rating Scale (ICARS) and a quantitative writing test. Cardiological evaluations included echocardiography, electrocardiography, and Holter monitoring. Oculomotor function was evaluated by electro-oculography to determine the frequency of square wave jerks.


RESULTS
The total ICARS score worsened during follow-up, whether or not the patients were treated with idebenone (1.93 +/- 0.25 and 4.43 +/- 1.56 points per year, respectively). The total ICARS score increased faster in patients with onset before age 15 years compared with the others (2.6 +/- 0.4 [n = 51] vs 1.1 +/- 0.3 [n = 37]; P = .05). The posture subscore increased faster in patients able to stand at baseline, who also had shorter disease durations than patients unable to stand (1.25 +/- 0.12 vs 0.47 +/- 0.22 point per year; P<.001). Neurological progression was underestimated, however, by the ICARS scores, which reached a plateau in patients with long disease durations. Oculomotor function slightly deteriorated (0.09 +/- 0.02 Hz per year; P<.001). Left ventricular mass index decreased (-4.1 +/- 1.5 g/m(2) per year; P = .008), as did ejection fraction (-1.32% +/- 0.29% per year; P<.001).


CONCLUSIONS
The neurological condition of FA patients deteriorated slowly over time, even with idebenone treatment. Although cardiac hypertrophy decreased under treatment, cardiac function did not improve. The ICARS scale is not appropriate to evaluate the progression of FA in patients with long disease durations. Additional quantitative measures may improve the reliability of this scale.
Ribaï
Pascale
P
Department of Genetics, Salpêtrière Medical School, Pierre and Marie Curie University, Paris, France.
Pousset
Françoise
F
Tanguy
Marie-Laure
ML
Rivaud-Pechoux
Sophie
S
Le Ber
Isabelle
I
Gasparini
Franchesca
F
Charles
Perrine
P
Béraud
Anne-Sophie
AS
Schmitt
Michele
M
Koenig
Michel
M
Mallet
Alain
A
Brice
Alexis
A
Dürr
Alexandra
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000627:therapeutic use; D016227:Benzoquinones / Q000627:therapeutic use*; D018450:Disease Progression; D004452:Echocardiography; D015716:Electrocardiography, Ambulatory; D004585:Electrooculography / Q000379:methods; D005500:Follow-Up Studies; D005621:Friedreich Ataxia / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D033862:Iron-Binding Proteins / Q000235:genetics; D008875:Middle Aged; D009460:Neurologic Examination; D010297:Paris; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D019680:Trinucleotide Repeat Expansion; D014451:Ubiquinone / Q000031:analogs & derivatives; D000096923:Frataxin
D000975:Antioxidants; D016227:Benzoquinones; D033862:Iron-Binding Proteins; D014451:Ubiquinone; D000096923:Frataxin; C036619:idebenone