Effects of Methylphenidate on Cerebral Glucose Metabolism in Patients With Impaired Consciousness After Acquired Brain Injury

Objectives: To evaluate the effects of methylphenidate on cerebral glucose metabolism in patients with impaired consciousness after acquired brain injury. Methods: Fourteen patients with impaired consciousness after acquired brain injury were enrolled in our study. We evaluated the level of consciousness with the Glasgow Coma Scale upon initial evaluation and at the 6-week follow-up after methylphenidate medication (0.3 mg/kg per day, which was administered twice daily). Positron emission tomography was performed before and after 6 weeks of medication, and the effects of methylphenidate on cerebral glucose metabolism were analyzed using statistical parametric mapping. Results: The statistical parametric mapping analysis indicated that significant increases of the cerebral glucose metabolism after methylphenidate therapy, compared with the initial positron emission tomographic image, were most evident in the left precuneus, the right posterior cingulated and the right retrosplenial cortices, and the right inferior parietal cortex (P < 0.001). In addition, cerebral glucose metabolism was significantly increased in the right precuneus, the right superior and middle temporal gyri, and bilateral middle occipital gyri (P < 0.005). In the correlation analysis, improvement of the Glasgow Coma Scale scores after methylphenidate medication was significantly associated with increased cerebral glucose metabolism in the bilateral precuneus, the bilateral middle occipital gyri, and right middle frontal gyrus. Conclusions: Our findings suggest that the posteromedial parietal cortex, which is part of the neural network for consciousness, may be the relevant structure for the pharmacological response to methylphenidate treatment in patients with impaired consciousness after acquired brain injury.

[1]  J. Liepert Pharmacotherapy in restorative neurology , 2008, Current opinion in neurology.

[2]  A. Cavanna The Precuneus and Consciousness , 2007, CNS Spectrums.

[3]  I. Moppett,et al.  Traumatic brain injury: assessment, resuscitation and early management. , 2007, British journal of anaesthesia.

[4]  Steven Laureys,et al.  How should functional imaging of patients with disorders of consciousness contribute to their clinical rehabilitation needs? , 2006, Current opinion in neurology.

[5]  Kamyar Keramatian,et al.  Effect of methylphenidate on ICU and hospital length of stay in patients with severe and moderate traumatic brain injury , 2006, Clinical Neurology and Neurosurgery.

[6]  Bruce D. McCandliss,et al.  Possible axonal regrowth in late recovery from the minimally conscious state. , 2006, The Journal of clinical investigation.

[7]  A. Cavanna,et al.  The precuneus: a review of its functional anatomy and behavioural correlates. , 2006, Brain : a journal of neurology.

[8]  F. Servadei Coma scales , 2006, The Lancet.

[9]  S. Sockalingam,et al.  Review of Awakening Agents , 2005, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[10]  B. Kosofsky,et al.  Methylphenidate and MK-801, an N-methyl-d-aspartate receptor antagonist: shared biological properties , 2004, Neuroscience.

[11]  H. Sackeim,et al.  Parietal cortex and representation of the mental Self. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[12]  B. Leonard,et al.  Methylphenidate: a review of its neuropharmacological, neuropsychological and adverse clinical effects , 2004, Human psychopharmacology.

[13]  M. Kajs‐Wyllie Ritalin Revisited: Does It Really Help in Neurological Injury? , 2002, The Journal of neuroscience nursing : journal of the American Association of Neuroscience Nurses.

[14]  G. Shulman,et al.  INAUGURAL ARTICLE by a Recently Elected Academy Member:A default mode of brain function , 2001 .

[15]  T. Challman,et al.  Methylphenidate: its pharmacology and uses. , 2000, Mayo Clinic proceedings.

[16]  Alan C. Evans,et al.  Brain Mechanisms of Propofol-Induced Loss of Consciousness in Humans: a Positron Emission Tomographic Study , 1999, The Journal of Neuroscience.

[17]  C. Phillips,et al.  Impaired Effective Cortical Connectivity in Vegetative State: Preliminary Investigation Using PET , 1999, NeuroImage.

[18]  M. Fetters,et al.  Methylphenidate in the treatment of coma. , 1997, The Journal of family practice.

[19]  Z. Khachaturian,et al.  Involvement of both cholinergic and catecholaminergic pathways in the central action of methylphenidate: A study utilizing lead-exposed rats , 1977, Psychopharmacology.

[20]  B Jennett,et al.  PREDICTING OUTCOME IN INDIVIDUAL PATIENTS AFTER SEVERE HEAD INJURY , 1976, The Lancet.

[21]  B. Jennett,et al.  Assessment of coma and impaired consciousness. A practical scale. , 1974, Lancet.

[22]  F. Servadei Coma scales. Commentary , 2006 .

[23]  Steven Laureys,et al.  Posterior cingulate, precuneal and retrosplenial cortices: cytology and components of the neural network correlates of consciousness. , 2005, Progress in brain research.

[24]  R. Lobato,et al.  [Prognostic factors in severe head injury]. , 2004, Neurocirugia.

[25]  T. Paus,et al.  Cerebral Mechanisms of Hypnotic Induction and Suggestion , 1999, Journal of Cognitive Neuroscience.

[26]  J. A. Frost,et al.  Conceptual Processing during the Conscious Resting State: A Functional MRI Study , 1999, Journal of Cognitive Neuroscience.

[27]  N. Mann,et al.  Amantadine: a potential treatment for the minimally conscious state. , 1998, Brain injury.

[28]  D. Cifu,et al.  Methylphenidate effect on attention deficit in the acutely brain-injured adult. , 1996, Archives of physical medicine and rehabilitation.

[29]  R. Ferguson,et al.  Letter: Lymphoid cells in jejunal mucosa. , 1975, Lancet.