Improved neurological function in a patient with complete spinal cord injury through bone marrow mesenchymal stem cells implantation: a case report.

Aim: Spinal cord injury (SCI) can cause severe disability. Several clinical trials of stem-cell based therapies are ongoing. We describe our experience of bone marrow mesenchymal stem cell (BMSC) therapy in a patient with complete SCI in the chronic stage. Case report: A 25-year-old man with complete SCI at T6 level presented with paraplegia for 5 years. We transplanted autologous BMSCs intramedullary. After 12 months follow-up, his Barthel index score was noticeably improved from severe to moderate dependency, and the sensation level improved from T7 to S5, but no improvement of motor function. Conclusion: Autologous BMSCs are potentially safe for patients with complete SCI in the chronic stage and may improve neurological function and quality of life.

A Role for Endoplasmic Reticulum Stress in Intracerebral Hemorrhage.

The endoplasmic reticulum (ER) is an intracellular organelle that performs multiple functions, such as lipid biosynthesis, protein folding, and maintaining intracellular calcium homeostasis. Thus, conditions wherein the ER is unable to fold proteins is defined as ER stress, and an inbuilt quality control mechanism, called the unfolded protein response (UPR), is activated during ER stress, which serves as a recovery system that inhibits protein synthesis. Further, based on the severity of ER stress, the response could involve both proapoptotic and antiapoptotic phases. Intracerebral hemorrhage (ICH) is the second most common subtype of cerebral stroke and many lines of evidence have suggested a role for the ER in major neurological disorders. The injury mechanism during ICH includes hematoma formation, which in turn leads to inflammation, elevated intracranial pressure, and edema. A proper understanding of the injury mechanism(s) is required to effectively treat ICH and closing the gap between our current understanding of ER stress mechanisms and ICH injury can lead to valuable advances in the clinical management of ICH.

Dorsolateral subthalamic neuronal activity enhanced by median nerve stimulation characterizes Parkinson's disease during deep brain stimulation with general anesthesia.

OBJECT: Deep brain stimulation (DBS) surgery under general anesthesia is an alternative option for patients with Parkinson's disease (PD). However, few studies are available that report whether neuronal firing can be accurately recorded during this condition. In this study the authors attempted to characterize the neuronal activity of the subthalamic nucleus (STN) and elucidate the influence of general anesthetics on neurons during DBS surgery in patients with PD. The benefit of median nerve stimulation (MNS) for localization of the dorsolateral subterritory of the STN, which is involved in sensorimotor function, was explored. METHODS: Eight patients with PD were anesthetized with desflurane and underwent contralateral MNS at the wrist during microelectrode recording of the STN. The authors analyzed the spiking patterns and power spectral density (PSD) of the background activity along each penetration track and determined the spatial correlation to the target location, estimated mated using standard neurophysiological procedures. RESULTS: The dorsolateral STN spiking pattern showed a more prominent bursting pattern without MNS and more oscillation with MNS. In terms of the neural oscillation of the background activity, beta-band oscillation dominated within the sensorimotor STN and showed significantly more PSD during MNS (p < 0.05). CONCLUSIONS: Neuronal firing within the STN could be accurately identified and differentiated when patients with PD received general anesthetics. Median nerve stimulation can enhance the neural activity in beta-band oscillations, which can be used as an index to ensure optimal electrode placement via successfully tracked dorsolateral STN topography.

Acute stimulation effect of the ventral capsule/ventral striatum in patients with refractory obsessive-compulsive disorder - a double-blinded trial.

OBJECTIVE: Deep-brain stimulation (DBS) for treating refractory obsessive-compulsive disorder (OCD) has shown positive results in small clinical trials. Ventral capsule/ventral striatum (VC/VS) is one of the promising targets; however, whether or not acute stimulation test can provide substantial information for chronic stimulation is not yet known. We evaluated postoperative test stimulation and examined the relationship of acute simulation-induced smile/laughter and 15-month clinical outcome. METHODS: Four adult patients with refractory OCD were implanted with Model 3387 leads bilaterally in an area of VC/VS. Postoperative test stimulation was performed at least 2 weeks after surgery. We performed double-blinded postoperative test stimulation with different contact and voltage. The relationship of stimulation-induced smile/laughter and chronic response was examined. RESULTS: Patients presented smile, laughter, euphoria, increased heart rate, increased blood pressure, smell, chest vibration, dizziness, nausea, heat, or increased sexual drive during acute stimulation. We found that the higher the percentage of smile/laughter (34.3%, 31.3%, 56.3%, and 12.5% for four cases), the greater the reduction in the Yale-Brown Obsessive Compulsive Scale (30.6%, 38.9%, 58.8%, and 7.7% respectively at 15-month DBS). CONCLUSION: This study showed that acute DBS of the VC/VS might cause mood change, cardiovascular, sensory, or motor effects. These effects were transient or habituated over six months. We suggest stimulation-induced smile/laughter may be a possible predictor for long-term DBS outcome. Larger studies, genetic studies, and imaging studies are needed to evaluate the effects of different parameters and possible predictors in the treatment of OCD.

Long-term outcome of young onset Parkinson's disease after subthalamic stimulation--a cross-sectional study.

OBJECTIVE: Age of onset is considered a poor prognostic factor for subthalamic deep brain stimulation (STN-DBS) outcome in the case of Parkinson's disease (PD). The goal of current study is to identify the long-term impact of STN-DBS for young onset PD (YOPD) patients. METHODS: 17 YOPD patients with a mean disease onset at 32.3 years were prospectively followed up at 1, 2, 5 and 7 years after STN-DBS. Unified Parkinson's disease rating scale (UPDRS) was evaluated in 4 combinations of Med/DBS on/off. RESULTS: UPDRS part II-IV improved significantly 7 years after operation. While a slowly progressive worsening of levodopa response on part III, synergistic effect of medication and stimulation consistently improves motor disabilities. STN-DBS could remarkably reduce levodopa equivalent daily dose at 7 years. The morbidity rates were low. However, these patients seem to have more transient stimulation dyskinesia (47.1%) and dopamine dysregulation syndrome (11.8%) after surgery. CONCLUSIONS: STN-DBS remains effective to improve motor disabilities over 7 years for YOPD and is a safe procedure concerning cognitive outcome and morbidity. However, stimulation dyskinesia and dopamine dysregulation syndrome deserve attention for the causal relationship between DBS surgery and behavioral outcomes.

Pilot study of deep brain stimulation in refractory obsessive-compulsive disorder ethnic Chinese patients.

AIMS: Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) is a promising alternative to ablative surgery in treatment of refractory obsessive-compulsive disorder (OCD). A pilot study was conducted to assess 15-month outcomes of DBS in patients with refractory OCD in Taiwan. METHODS: Four adult patients with a 3-year or more history of refractory OCD (Yale-Brown Obsessive-Compulsive Scale [Y-BOCS] score of at least 28) met the criteria for DBS surgery. DBS electrodes were implanted bilaterally in the VC/VS. Stimulation was adjusted for therapeutic benefit and absence of adverse effects. Psychiatric evaluation was conducted preoperatively, postoperatively, and at follow up at every 3 months for 15 months. Primary outcome measure was Y-BOCS. Secondary outcomes included the Hamilton Depression Rating Scale (HAM-D), and the Global Assessment of Function Scale. RESULTS: Mean severity of OCD was a Y-BOCS score of 36.3 ± 2.1. At the end of 15 months' follow up, there was a 33.06% decrease in OCD severity (P = 0.001). Similar findings were seen for HAM-D (32.51% reduction, P = 0.005), and Global Assessment of Function Scale (31.03% increase, P = 0.026). In terms of adverse effects, two patients suffered from hypomania episodes after several weeks of DBS stimulation, and one had transient hypomania-like syndrome during DBS initial programming. One patient (Case 1) had an allergic reaction to implantation of the pulse generator in the chest, and another patient (Case 3) exhibited vertigo. CONCLUSIONS: We confirm that DBS of the VC/VS appears to be beneficial for improvements in function and mood among patients with treatment-resistant OCD. Compared to previous studies examining the therapeutic effects of DBS, no serious adverse effects were observed.

Subthalamic deep brain stimulation in Parkinson's disease under different anesthetic modalities: a comparative cohort study.

BACKGROUND: The efficacy and feasibility of bilateral subthalamic deep brain stimulation (STN-DBS) for Parkinson's disease (PD) under general anesthesia (GA) has not been evaluated. OBJECTIVE: We compared the outcome of patients under GA with those who were operated on under local anesthesia (LA). MATERIAL AND METHODS: Thirty-three patients were assigned to the GA group (desflurane) and 19 patients were assigned to the LA group. Microelectrode recording (MER) was performed in both groups. The surgical outcomes of the patients were evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) after at least 12 months after surgery. RESULTS: Postoperatively, there was no significant difference on the UPDRS scores in either groups. A significant deterioration in cognitive function in the GA group was observed (p = 0.017). The recorded electrode coordinates, the average tracts for the MER, and STN depth were comparable in both groups. The overall incidence of adverse effects did not show any difference except that the incidence of sialorrhea and dysarthria was significantly higher in the GA group. CONCLUSION: Desflurane GA was shown to be a good alternative anesthetic method for PD patients undergoing DBS. Although the motor outcomes were comparable, a significant cognitive decline may be seen in the GA group with a higher occurrence of stimulation side effects.

Targeting the subthalamic nucleus for deep brain stimulation--a comparative study between magnetic resonance images alone and fusion with computed tomographic images.

BACKGROUND: The aim of this study is to determine whether stereotactic computed tomographic (CT) images fused with magnetic resonance images (MRI) is superior to stereotactic MRI alone in accuracy for targeting the subthalamic nucleus (STN) in deep brain stimulation (DBS). METHODS: During 2006 to 2007, 21 consecutive patients with Parkinson's disease were enrolled in this retrospective cohort study. CT Fusion group included 10 patients who underwent 20 procedures of STN-DBS under MRI-directed targeting in which the MRIs were fused to stereotactic CT images for surgical coordinates. MRI group included 11 patients who underwent 20 procedures under MRI-directed targeting alone. RESULTS: After DBS surgery, in comparison to baseline levodopa (L-dopa) OFF, Unified Parkinson Disease Rating Scale, Part III scores improved by 43.6% ± 20.3% and 39.0% ± 15.6% (P = 0.60) in CT Fusion group and MRI group, respectively (L-dopa OFF/DBS ON). The mean decrease in L-dopa equivalent daily dose was 38.9% ± 26.3% and 36.7% ± 30.5% (P = 0.87), respectively. Single microelectrode recording (MER) trajectory procedure was experienced in 65% of patients in the CT Fusion group (13/20) and 45% of patients in the MRI group (9/20). The mean recorded STN length from initial to final MER trajectory in the CT Fusion and MRI groups was 4.3 mm (standard deviation [SD] = 1.8 mm)/5.1 mm (SD = 0.5 mm) and 3.6 mm (SD = 1.7 mm) (P = 0.214)/4.5 mm (SD = 0.7 mm) (P = 0.006), respectively. The final recorded STN length was significantly longer in the CT Fusion group. CONCLUSIONS: In-frame-based stereotactic STN targeting, an image fusion technique between stereotactic CT and MRI, can record a significantly longer STN length through limited MER compared with MRI alone. Whether this could translate into better clinical outcome and less morbidity still need a large and randomized trial.

Prognostic factors of subthalamic stimulation in Parkinson's disease: a comparative study between short- and long-term effects.

BACKGROUND/AIMS: Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) has been shown to have long-term benefits in Parkinson's disease (PD). Through analyzing different variables, this study identified prognostic factors for the short- and long-term effects of STN-DBS. METHODS: Thirty-six PD patients underwent bilateral STN-DBS. Clinical evaluations were performed 1 month before and 3 months after surgery, with additional follow-up examinations for a mean of 31.3 months. RESULTS: There was a trend for long-term STN-DBS-induced improvements in the Unified Parkinson's Disease Rating Scale (UPDRS) part II and part III measures to be greater in younger patients. Preoperative levodopa responsiveness only led to consistent UPDRS part III improvement from STN-DBS at 3 months, and this predictive value did not exist in the long term. The preoperative levodopa response of tremor and axial symptoms in motor disability predicted long-term DBS effect only. Preoperative cognitive function positively correlated with postoperative improvement from DBS in UPDRS part III during long-term follow-up only. CONCLUSIONS: The prognostic factors for STN-DBS benefit were different for short- and long-term follow-ups. Good prognostic factors for long-term STN-DBS for PD patients were good cognitive function and tremor dominance. Poor prognostic factors were related to older age and non-dopaminergic-responsive axial disability.