Muscle Nogo-A expression is a prognostic marker in lower motor neuron syndromes.
OBJECTIVE
A proportion of patients with pure lower motor neuron syndrome (LMNS) progress to amyotrophic lateral sclerosis (ALS). Early detection of this progression is impossible, which delays the patient's access to treatment. Muscle expression of Nogo-A is a new candidate marker of ALS. We tested whether detection of Nogo-A in a muscle biopsy from patients with LMNS predicts progression to ALS.


METHODS
Thirty-three patients who had undergone a muscle biopsy during the diagnostic workup of spinal LMNS were observed for 12 months. Nogo-A expression was measured by Western blot in muscle biopsy samples and compared with the final diagnosis.


RESULTS
Nogo-A expression was detected in 17 patients and was absent in 16 patients. The detection of Nogo-A in muscle biopsy samples from LMNS patients correctly identified patients who further progressed to ALS with 91% accuracy, 94% sensitivity, and 88% specificity. In patients who later developed typical ALS, Nogo-A may be detected as early as 3 months after the onset of symptoms.


CONCLUSIONS
Nogo-A test is able to identify ALS early in the course of the disease when diagnosis is difficult, requiring further progression. Use of the test in clinical practice may shorten the delay before introduction of neuroprotective drugs or inclusion in clinical trials.
Pradat
Pierre-François
PF
Fédération des Maladies du Système Nerveux, Centre référent maladie rare SLA, Hôpital de la Pitié-Salpêtrière, 47-83 Boulevard de l'Hôpital, 75651 Paris, France.
Bruneteau
Gaelle
G
Gonzalez de Aguilar
Jose-Luis
JL
Dupuis
Luc
L
Jokic
Natasa
N
Salachas
François
F
Le Forestier
Nadine
N
Echaniz-Laguna
Andoni
A
Dubourg
Odile
O
Hauw
Jean-Jacques
JJ
Tranchant
Christine
C
Loeffler
Jean-Philippe
JP
Meininger
Vincent
V
D000328:Adult; D000368:Aged; D001706:Biopsy / Q000379:methods; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000378:metabolism* / Q000473:pathology*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009185:Myelin Proteins / Q000378:metabolism*; D000070798:Nogo Proteins; D011379:Prognosis; D012189:Retrospective Studies
D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603199:RTN4 protein, human