Akinetic Mutism Without a Structural Prefrontal Lesion

Akinetic mutism is characterized by profound apathy and a lack of verbal and motor output for action, despite preserved alertness. The condition usually follows bilateral damage to the medial frontal subcortical circuits. We report a 59-year-old right-handed woman who was admitted to the neurology ward with sudden-onset akinetic mutism. Her medical history included an ischemic stroke 3 years earlier, with residual anomia and mild agraphia but no motor dysfunction. On this admission, a cranial computed tomography scan disclosed an acute left superior cerebellar infarction embracing the vermis, and a prior left inferior parietal infarct. Electroencephalogram showed bilateral frontal delta-wave activity. Four weeks later, we performed a technetium-99m hexamethylpropyleneamine oxime single-photon emission computed tomography (Tc-99m-HMPAO SPECT) scan to study the patient's frontal lobe function. The SPECT scan revealed the causative bifrontal hypoperfusion, more prominent on the right, while the structurally evident cerebellar infarction was predictably masked by subacute hyperperfusion phenomenon. Contralateral frontal diaschisis is an established sequela of cerebellar infarction. Because this patient also had lesions in the left parietal region, her left prefrontal area was critically deprived of its major reciprocally connected cortical counterparts (right prefrontal and left parietal), and also became dysfunctional. Her resulting bilateral frontal dysfunction is a common cause of akinetic mutism

Can noninvasive brain stimulation enhance cognition in neuropsychiatric disorders?

Cognitive impairment is a core symptom of many neuropsychiatric diseases and a key contributor to the patient's quality of life. However, an effective therapeutic strategy has yet to be developed. Noninvasive brain stimulation techniques, namely transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), are promising techniques that are under investigation for a variety of otherwise treatment-resistant neuropsychiatric diseases. Notably, these tools can induce alterations in neural networks subserving cognitive operations and thus may provide a means for cognitive restoration. The purpose of this article is to review the available evidence concerning cognitive enhancing properties of noninvasive brain stimulation in neuropsychiatry. We specifically focus on major depression. Alzheimer's disease, schizophrenia, autism and attention deficit hyperactivity disorder (ADHD), where cognitive dysfunction is a major symptom and some studies have been completed with promising results. We provide a critical assessment of the available research and suggestions to guide future efforts

Noninvasive Brain Stimulation in Traumatic Brain Injury

Objective: To review novel techniques of noninvasive brain stimulation (NBS), which may have value in assessment and treatment of traumatic brain injury (TBI). Methods: Review of the following techniques: transcranial magnetic stimulation, transcranial direct current stimulation, low-level laser therapy, and transcranial Doppler sonography. Furthermore, we provide a brief overview of TMS studies to date. Main findings: We describe the rationale for the use of these techniques in TBI, discuss their possible mechanisms of action, and raise a number of considerations relevant to translation of these methods to clinical use. Depending on the stimulation parameters, NBS may enable suppression of the acute glutamatergic hyperexcitability following TBI and/or counter the excessive GABAergic effects in the subacute stage. In the chronic stage, brain stimulation coupled to rehabilitation may enhance behavioral recovery, learning of new skills, and cortical plasticity. Correlative animal models and comprehensive safety trials seem critical to establish the use of these modalities in TBI. Conclusions: Different forms of NBS techniques harbor the promise of diagnostic and therapeutic utility, particularly to guide processes of cortical reorganization and enable functional restoration in TBI. Future lines of safety research and well-designed clinical trials in TBI are warranted to determine the capability of NBS to promote recovery and minimize disability.Supported in part by a BBVA Translational Research Chair in Biomedicine, a grant from the International Brain Research Foundation (IBRF), and National Institutes of Health grant K 24 RR018875 to A.P.L., and grant PI082004 from the Instituto de Salud Carlos III. A.M.V.-H. is a Howard Hughes Medical Institute medical research training fellowMedicin

Safety and behavioral effects of high-frequency repetitive transcranial magnetic stimulation in stroke.

Background and purposeElectromagnetic brain stimulation might have value to reduce motor deficits after stroke. Safety and behavioral effects of higher frequencies of repetitive transcranial magnetic stimulation (rTMS) require detailed assessment.MethodsUsing an active treatment-only, unblinded, 2-center study design, patients with chronic stroke received 20 minutes of 20 Hz rTMS to the ipsilesional primary motor cortex hand area. Patients were assessed before, during the hour after, and 1 week after rTMS.ResultsThe 12 patients were 4.7+/-4.9 years poststroke (mean+/-SD) with moderate-severe arm motor deficits. In terms of safety, rTMS was well tolerated and did not cause new symptoms; systolic blood pressure increased from pre- to immediately post-rTMS by 7 mm Hg (P=0.043); and none of the behavioral measures showed a decrement. In terms of behavioral effects, modest improvements were seen, for example, in grip strength, range of motion, and pegboard performance, up to 1 week after rTMS. The strongest predictor of these motor gains was lower patient age.ConclusionsA single session of high-frequency rTMS to the motor cortex was safe. These results require verification with addition of a placebo group and thus blinded assessments across a wide spectrum of poststroke deficits and with larger doses of 20 Hz rTMS

Safety and behavioral effects of high-frequency repetitive transcranial magnetic stimulation in stroke.

Background and purposeElectromagnetic brain stimulation might have value to reduce motor deficits after stroke. Safety and behavioral effects of higher frequencies of repetitive transcranial magnetic stimulation (rTMS) require detailed assessment.MethodsUsing an active treatment-only, unblinded, 2-center study design, patients with chronic stroke received 20 minutes of 20 Hz rTMS to the ipsilesional primary motor cortex hand area. Patients were assessed before, during the hour after, and 1 week after rTMS.ResultsThe 12 patients were 4.7+/-4.9 years poststroke (mean+/-SD) with moderate-severe arm motor deficits. In terms of safety, rTMS was well tolerated and did not cause new symptoms; systolic blood pressure increased from pre- to immediately post-rTMS by 7 mm Hg (P=0.043); and none of the behavioral measures showed a decrement. In terms of behavioral effects, modest improvements were seen, for example, in grip strength, range of motion, and pegboard performance, up to 1 week after rTMS. The strongest predictor of these motor gains was lower patient age.ConclusionsA single session of high-frequency rTMS to the motor cortex was safe. These results require verification with addition of a placebo group and thus blinded assessments across a wide spectrum of poststroke deficits and with larger doses of 20 Hz rTMS