Autonomic dysfunction in ALS: a preliminary study on the effects of intrathecal BDNF.
This pilot study aimed at exploring the effects of intrathecally administered brain derived neurotrophic factor (BDNF) on autonomic functions in patients with ALS. A battery of autonomic sympathetic and parasympathetic tests was performed at baseline and after nine months of treatment in 10 ALS patients participating in a double-blind placebo-controlled phase II/III study of intrathecally administered BDNF. Results of patients treated with BDNF (25 or 150 microg/day) were compared to those receiving placebo. Sudomotor function and blood pressure response to handgrip significantly worsened during the treatment period (55.4+/-26.1 vs. 38.9+/-23.9 g/m(2)h, p<0.05; 20+/-6 vs. 13+/-4 microHg, p<0.05) whereas other sympathetic and all parasympathetic function tests only tended to be more abnormal at follow-up. Serum norepinephrine levels increased significantly during the nine-months observation period. The results of autonomic function tests were not different between patients treated with BDNF and placebo, but norepinephrine levels were higher in the BDNF group. We conclude that autonomic nervous system function deteriorates along with poorer motor performance independently from treatment with BDNF. The elevation of norepinephrine levels might reflect a non-specific up-regulation, and its association with BDNF an autocrine effect.
Beck
Marcus
M
Department of Neurology, ALS Study Group, Julius-Maximilians-University Wuerzburg, Germany. marcus.beck@mail.uni-wuerzburg.de
Flachenecker
Peter
P
Magnus
Tim
T
Giess
Ralf
R
Reiners
Karlheinz
K
Toyka
Klaus V
KV
Naumann
Markus
M
D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D001341:Autonomic Nervous System / Q000187:drug effects / Q000503:physiopathology; D001342:Autonomic Nervous System Diseases / Q000188:drug therapy* / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000627:therapeutic use*; D004311:Double-Blind Method; D004837:Epinephrine / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism; D013542:Sweat / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome
D019208:Brain-Derived Neurotrophic Factor; D009638:Norepinephrine; D004837:Epinephrine