title: The neurophysiological effects of single-dose theophylline in patients with chronic stroke: A double-blind, placebo-controlled, randomized cross-over study.
abstract: Reducing inhibitory neurotransmission with pharmacological agents is a potential approach for augmenting plasticity after stroke. Previous work in healthy subjects showed diminished intracortical inhibition after administration of theophylline.
  
  
  
  We assessed the effect of single-dose theophylline on intracortical and interhemispheric inhibition in patients with chronic stroke, in a double-blind, placebo-controlled, cross-over study.
  
  
  
  Eighteen subjects were randomly administered 300 mg of extended-release theophylline or placebo. Immediately and 5 hours following administration, transcranial magnetic stimulation was used to assess bihemispheric resting motor threshold, short-interval intracortical inhibition, long-interval intracortical inhibition, and interhemispheric inhibition. Adverse effects on cardiovascular, neurological, and motor performance outcomes were also surveilled. Change between morning and afternoon sessions were compared across conditions. One week later, patients underwent the same assessments after crossing over to the opposite experimental condition. Subjects and investigators were blinded to the experimental condition during data acquisition and analysis.
  
  
  
  For both hemispheres, changes in intracortical or interhemispheric neurophysiology were comparable under theophylline and placebo conditions. Theophylline induced no adverse neurological, cardiovascular, or motor performance effects. For both conditions and hemipsheres, the baseline level of inhibition inversely correlated with its change between sessions: less baseline inhibition (i.e. disinhibition) was associated with a strengthening in inhibition over the day, and vice versa.
  
  
  
  A single dose of theophylline is well-tolerated by patients with chronic stroke, but does not alter cortical excitability. The inverse relationship between baseline inhibition and its change suggests the existence of a homeostatic process. The lack of effect on cortical inhibition may be related to an insufficiently long exposure to theophylline, or to differential responsiveness of disinhibited neural circuitry in patients with stroke.
authors: Departments of Neurology and Rehabilitation and Regenerative Medicine, Motor Performance Laboratory, Columbia University Medical Center, New York, NY, USA.
authors: Heidi M
authors: HM
authors: Schambra
authors: Departments of Neurology and Rehabilitation and Regenerative Medicine, Motor Performance Laboratory, Columbia University Medical Center, New York, NY, USA.
authors: Isis E
authors: IE
authors: Martinez-Hernandez
authors: Department of Neurology, Richard and Jenny Levine Cerebral Localization Laboratory, Columbia University Medical Center, New York, NY, USA.
authors: Kevin J
authors: KJ
authors: Slane
authors: Department of Neurology, Richard and Jenny Levine Cerebral Localization Laboratory, Columbia University Medical Center, New York, NY, USA.
authors: Amelia K
authors: AK
authors: Boehme
authors: Department of Neurology, Richard and Jenny Levine Cerebral Localization Laboratory, Columbia University Medical Center, New York, NY, USA.
authors: Randolph S
authors: RS
authors: Marshall
authors: Department of Neurology, Richard and Jenny Levine Cerebral Localization Laboratory, Columbia University Medical Center, New York, NY, USA.
authors: Ronald M
authors: RM
authors: Lazar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease; D018592:Cross-Over Studies; D004311:Double-Blind Method; D019054:Evoked Potentials, Motor / Q000502:physiology*; D005260:Female; D005385:Fingers / Q000294:innervation; D007839:Functional Laterality / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000187:drug effects* / Q000503:physiopathology; D009433:Neural Inhibition / Q000502:physiology; D011597:Psychomotor Performance / Q000502:physiology; D020521:Stroke / Q000188:drug therapy* / Q000503:physiopathology*; D013806:Theophylline / Q000627:therapeutic use*; D050781:Transcranial Magnetic Stimulation; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D014665:Vasodilator Agents; D013806:Theophylline
keywords: Recovery of function; cerebral infarction; homeostasis; motor cortex; transcranial magnetic stimulation