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Andres Lozano, William Hutchison, Zelma Kiss, Ronald Tasker, Karen Davis, and Jonathan Dostrovsky

✓ Methods for localizing the posteroventral globus pallidus internus are described. The authors' techniques include the use of microelectrodes to record single-unit activity and to microstimulate in human pallidum and its surrounding structures. This technique allows a precise determination of the locations of characteristic cell types in sequential trajectories through the external and internal segments of the pallidum. The location of the optic tract can be determined from microstimulation-evoked visual sensations and recordings of flash-evoked potentials. In addition, microstimulation-evoked motor and sensory responses allow the internal capsule to be identified. The data collected using this technique are an important adjunct to selecting optimum sites to place electrocoagulation lesions for stereotactic posteroventral pallidotomy for refractory Parkinson's disease.

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Karen D. Davis, Ethan Taub, Frank Duffner, Andres M. Lozano, Ronald R. Tasker, Sylvain Houle, and Jonathan O. Dostrovsky

Object

Deep brain stimulation (DBS) of the sensory thalamus has been used to treat chronic, intractable pain. The goal of this study was to investigate the thalamocortical pathways activated during thalamic DBS.

Methods

The authors compared positron emission tomography (PET) images obtained before, during, and after DBS in five patients with chronic pain. Two of the five patients reported significant DBS-induced pain relief during PET scanning, and the remaining three patients did not report any analgesic effect of DBS during scanning. The most robust effect associated with DBS was activation of the anterior cingulate cortex (ACC). An anterior ACC activation was sustained throughout the 40 minutes of DBS, whereas a more posteriorly located ACC activation occurred at a delay after onset of DBS, although these activations were not dependent on the degree of pain relief reported during DBS. However, implications specific to the analgesic effect of DBS require further study of a larger, more homogeneous patient population. Additional effects of thalamic DBS were detected in motor-related regions (the globus pallidus, cortical area 4, and the cerebellum) and visual and association cortical areas.

Conclusions

The authors demonstrate that the ACC is activated during thalamic DBS in patients with chronic pain.

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Karen D. Davis, Ethan Taub, Frank Duffner, Andres M. Lozano, Ronald R. Tasker, Sylvain Houle, and Jonathan O. Dostrovsky

Object. Deep brain stimulation (DBS) of the sensory thalamus has been used to treat chronic, intractable pain. The goal of this study was to investigate the thalamocortical pathways activated during thalamic DBS.

Methods. The authors compared positron emission tomography (PET) images obtained before, during, and after DBS in five patients with chronic pain. Two of the five patients reported significant DBS-induced pain relief during PET scanning, and the remaining three patients did not report any analgesic effect of DBS during scanning. The most robust effect associated with DBS was activation of the anterior cingulate cortex (ACC). An anterior ACC activation was sustained throughout the 40 minutes of DBS, whereas a more posteriorly located ACC activation occurred at a delay after onset of DBS, although these activations were not dependent on the degree of pain relief reported during DBS. However, implications specific to the analgesic effect of DBS require further study of a larger, more homogeneous patient population. Additional effects of thalamic DBS were detected in motor-related regions (the globus pallidus, cortical area 4, and the cerebellum) and visual and association cortical areas.

Conclusions. The authors demonstrate that the ACC is activated during thalamic DBS in patients with chronic pain.

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Charles H. Tator, Hannah S. Davis, Paul A. Dufort, Maria Carmella Tartaglia, Karen D. Davis, Ahmed Ebraheem, and Carmen Hiploylee

OBJECTIVE

The objective of this study was to determine the demographics and predictors of postconcussion syndrome (PCS) in a large series of patients using a novel definition of PCS.

METHODS

The authors conducted a retrospective cohort study of 284 consecutive concussed patients, 221 of whom had PCS on the basis of at least 3 symptoms persisting at least 1 month. This definition of PCS was uniformly employed and is unique in accepting an expanded list of symptoms, in shortening the postconcussion interval to 1 month from 3 months, and in excluding those with focal injuries such as hemorrhages and contusions.

RESULTS

The 221 cases showed considerable heterogeneity in clinical features of PCS. They averaged 3.3 concussions, with a range of 0 to 12 or more concussions, and 62.4% occurred during sports and recreation. The median duration of PCS was 7 months at the time of examination, with 11.8% lasting more than 2 years, and 23.1% with PCS had only 1 concussion. The average patient age was 27 years (range 10–74 years). The average number of persistent symptoms was 8.1; 26.2% had a previous psychiatric condition, attention-deficit disorder/attention-deficit hyperactivity disorder, a learning disability, or previous migraine headaches. The prevalence of arachnoid cysts and Chiari malformation in PCS exceeded the general population. Additionally, involvement in litigation, presence of extracranial injuries, amnesia and/or loss of consciousness, and female sex were predictive of reporting a high number of symptoms. A prior history of psychiatric conditions or migraines, cause of injury, number of previous concussions, and age did not significantly predict symptom number. Only the number of symptoms reported predicted the duration of PCS. To predict the number of symptoms for those who fulfilled PCS criteria according to the International Classification of Diseases, 10th Revision (ICD-10), and the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV), the number of previous concussions was significant.

CONCLUSIONS

PCS is commonly associated with multiple concussions, but 23.1% in the present series occurred after only 1 concussion. Most patients with PCS had multiple symptoms persisting for months or years. The median duration of PCS was 7 months, with a range up to 26 years. In only 11.3%, the PCS had ended at the time of consultation. Not all predictors commonly cited in the literature align with the findings in this study. This is likely due to differences in the definitions of PCS used in research. These results suggest that the use of ICD-10 and DSM-IV to diagnose PCS may be biased toward those who are vulnerable to concussions or with more severe forms of PCS. It is thus important to redefine PCS based on evidence-based medicine.

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Ali R. Rezai, Andres M. Lozano, Adrian P. Crawley, Michael L. G. Joy, Karen D. Davis, Chun L. Kwan, Jonathan O. Dostrovsky, Ronald R. Tasker, and David J. Mikulis

The utility of functional magnetic resonance (fMR) imaging in patients with implanted thalamic electrodes has not yet been determined. The aim of this study was to establish the safety of performing fMR imaging in patients with thalamic deep brain stimulators and to determine the value of fMR imaging in detecting cortical and subcortical activity during stimulation.

Functional MR imaging was performed in three patients suffering from chronic pain and two patients with essential tremor. Two of the three patients with pain had undergone electrode implantation in the thalamic sensory ventralis caudalis (Vc) nucleus and the other had undergone electrode implantation in both the Vc and the periventricular gray (PVG) matter. Patients with tremor underwent electrode implantation in the ventralis intermedius (Vim) nucleus. Functional MR imaging was performed during stimulation by using a pulse generator connected to a transcutaneous extension lead. Clinically, Vc stimulation evoked paresthesias in the contralateral body, PVG stimulation evoked a sensation of diffuse internal body warmth, and Vim stimulation caused tremor arrest.

Functional images were acquired using a 1.5-tesla MR imaging system. The Vc stimulation at intensities provoking paresthesias resulted in activation of the primary somatosensory cortex (SI). Stimulation at subthreshold intensities failed to activate the SI. Additional stimulation-coupled activation was observed in the thalamus, the secondary somatosensory cortex (SII), and the insula. In contrast, stimulation of the PVG electrode did not evoke paresthesias or activate the SI, but resulted in medial thalamic and cingulate cortex activation. Stimulation in the Vim resulted in thalamic, basal ganglia, and SI activation.

An evaluation of the safety of the procedure indicated that significant current could be induced within the electrode if a faulty connecting cable (defective insulation) came in contact with the patient. Simple precautions, such as inspection of wires for fraying and prevention of their contact with the patient, enabled the procedure to be conducted safely. Clinical safety was further corroborated by performing 86 MR studies in patients in whom electrodes had been implanted with no adverse clinical effects.

This is the first report of the use of fMR imaging during stimulation with implanted thalamic electrodes. The authors' findings demonstrate that fMR imaging can safely detect the activation of cortical and subcortical neuronal pathways during stimulation and that stimulation does not interfere with imaging. This approach offers great potential for understanding the mechanisms of action of deep brain stimulation and those underlying pain and tremor generation.

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Ali R. Rezai, Andres M. Lozano, Adrian P. Crawley, Michael L. G. Joy, Karen D. Davis, Chun L. Kwan, Jonathan O. Dostrovsky, Ronald R. Tasker, and David J. Mikulis

✓ The utility of functional magnetic resonance (fMR) imaging in patients with implanted thalamic electrodes has not yet been determined. The aim of this study was to establish the safety of performing fMR imaging in patients with thalamic deep brain stimulators and to determine the value of fMR imaging in detecting cortical and subcortical activity during stimulation.

Functional MR imaging was performed in three patients suffering from chronic pain and two patients with essential tremor. Two of the three patients with pain had undergone electrode implantation in the thalamic sensory ventralis caudalis (Vc) nucleus and the other had undergone electrode implantation in both the Vc and the periventricular gray (PVG) matter. Patients with tremor underwent electrode implantation in the ventralis intermedius (Vim) nucleus. Functional MR imaging was performed during stimulation by using a pulse generator connected to a transcutaneous extension lead. Clinically, Vc stimulation evoked paresthesias in the contralateral body, PVG stimulation evoked a sensation of diffuse internal body warmth, and Vim stimulation caused tremor arrest.

Functional images were acquired using a 1.5-tesla MR imaging system. The Vc stimulation at intensities provoking paresthesias resulted in activation of the primary somatosensory cortex (SI). Stimulation at subthreshold intensities failed to activate the SI. Additional stimulation-coupled activation was observed in the thalamus, the secondary somatosensory cortex (SII), and the insula. In contrast, stimulation of the PVG electrode did not evoke paresthesias or activate the SI, but resulted in medial thalamic and cingulate cortex activation. Stimulation in the Vim resulted in thalamic, basal ganglia, and SI activation.

An evaluation of the safety of the procedure indicated that significant current could be induced within the electrode if a faulty connecting cable (defective insulation) came in contact with the patient. Simple precautions, such as inspection of wires for fraying and prevention of their contact with the patient, enabled the procedure to be conducted safely. Clinical safety was further corroborated by performing 86 MR studies in patients in whom electrodes had been implanted with no adverse clinical effects.

This is the first report of the use of fMR imaging during stimulation with implanted thalamic electrodes. The authors' findings demonstrate that fMR imaging can safely detect the activation of cortical and subcortical neuronal pathways during stimulation and that stimulation does not interfere with imaging. This approach offers great potential for understanding the mechanisms of action of deep brain stimulation and those underlying pain and tremor generation.