Non-invasively enhanced intracranial transplantation of mesenchymal stem cells using focused ultrasound mediated by overexpression of cell-adhesion molecules

Although there have been reports of promising results regarding the transplantation of mesenchymal stem cells (MSCs) for neurodegenerative diseases through the use of neuronal differentiation or control of the microenvironment, traditional surgical transplantation methods like parenchymal or intravenous injection have limitations such as secondary injuries in the brain, infection, and low survival rate of stem cells in the target site. Focused ultrasound (FUS) treatment is an emerging modality for the treatment of brain diseases, including neurodegenerative disorders. The various biological effects of FUS treatment have been investigated; therefore, the goal is now to improve the delivery efficiency and function of MSCs by capitalizing on the advantages of FUS. In this study, we demonstrated that FUS increases MSC transplantation into brain tissue by >2-fold, and that this finding might be related to the activation of intercellular adhesion molecule-1 in endothelial and subendothelial cells and vascular adhesion molecule-1 in endothelial cells.ope

Magnetic Resonance-Guided Focused Ultrasound in Neurosurgery: Taking Lessons From the Past to Inform the Future

Magnetic resonance-guided focused ultrasound (MRgFUS) is a new emerging neurosurgical procedure applied in a wide range of clinical fields. It can generate high-intensity energy at the focal zone in deep body areas without requiring incision of soft tissues. Although the effectiveness of the focused ultrasound technique had not been recognized because of the skull being a main barrier in the transmission of acoustic energy, the development of hemispheric distribution of ultrasound transducer phased arrays has solved this issue and enabled the performance of true transcranial procedures. Advanced imaging technologies such as magnetic resonance thermometry could enhance the safety of MRgFUS. The current clinical applications of MRgFUS in neurosurgery involve stereotactic ablative treatments for patients with essential tremor, Parkinson's disease, obsessive-compulsive disorder, major depressive disorder, or neuropathic pain. Other potential treatment candidates being examined in ongoing clinical trials include brain tumors, Alzheimer's disease, and epilepsy, based on MRgFUS abilities of thermal ablation and opening the blood-brain barrier. With the development of ultrasound technology to overcome the limitations, MRgFUS is gradually expanding the therapeutic field for intractable neurological disorders and serving as a trail for a promising future in noninvasive and safe neurosurgical care.ope

Surgical Anatomy of the Temporal Lobe

The temporal lobe is a unique structure in the human brain and one of the most important structures involved in the surgical treatment of intractable epilepsy. Knowledge of the temporal lobe??s structures and function allow us to better understand the complex phenomenology of temporal lobe seizures and the positive and negative effects of surgical resections in the area. We reviewed the parenchymal and vascular anatomy and the white matter tracts of temporal lobe, and the relationships to surrounding structures such as dural structures and cistern.ope

Skull Factors Affecting Outcomes of Magnetic Resonance-Guided Focused Ultrasound for Patients With Essential Tremor

Purpose: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy has become a standard treatment for medically intractable essential tremor (ET). Skull density ratio (SDR) and skull volume in patients with ET are currently considered useful indicators of the successful application of MRgFUS. We compared the clinical outcomes of MRgFUS thalamotomy with SDR above 0.4 and 0.45. We also described patterns of SDR and skull volume in Korean patients with ET who were eligible to be screened for MRgFUS. Materials and methods: In screening 318 ET patients, we evaluated patterns of skull density and skull volume according to age and sex. Fifty patients with ET were treated with MRgFUS. We investigated the effects of SDR and skull volume on treatment parameters and the outcomes of ET. Results: The mean SDR of the 318 ET patients was 0.45±0.11, and that for skull volume was 315.74±40.95 cm³. The male patients had a higher SDR than female patients (p=0.047). Skull volume significantly decreased with aging. SDR and skull volume exhibited a linear negative relationship. Among therapeutic parameters, maximal temperature was positively related to SDR, while sonication number was not related to either SDR or skull volume. Tremor outcome was also not related to SDR or skull volume. Conclusion: SDR varied widely from 0.11 to 0.73, and men had a higher SDR. Therapeutic parameters and clinical outcomes were not affected by SDR or skull volume.ope

Factors Related to Successful Energy Transmission of Focused Ultrasound Through a Skull : A Study in Human Cadavers and Its Comparison With Clinical Experiences

Objective: Although magnetic resonance guided focused ultrasound (MRgFUS) has been used as minimally invasive and effective neurosurgical treatment, it exhibits some limitations, mainly related to acoustic properties of the skull barrier. This study was undertaken to identify skull characteristics that contribute to optimal ultrasonic energy transmission for MRgFUS procedures. Methods: For ex vivo skull experiments, various acoustic fields were measured under different conditions, using five non-embalmed cadaver skulls. For clinical skull analyses, brain computed tomography data of 46 patients who underwent MRgFUS ablations (18 unilateral thalamotomy, nine unilateral pallidotomy, and 19 bilateral capsulotomy) were retrospectively reviewed. Patients' skull factors and sonication parameters were comparatively analyzed with respect to the cadaveric skulls. Results: Skull experiments identified three important factors related skull penetration of ultrasound, including skull density ratio (SDR), skull volume, and incidence angle of the acoustic rays against the skull surface. In clinical results, SDR and skull volume correlated with maximal temperature (Tmax) and energy requirement to achieve Tmax (p<0.05). In addition, considering the incidence angle determined by brain target location, less energy was required to reach Tmax in the central, rather than lateral targets particularly when compared between thalamotomy and capsulotomy (p<0.05). Conclusion: This study reconfirmed previously identified skull factors, including SDR and skull volume, for successful MRgFUS; it identified an additional factor, incidence angle of acoustic rays against the skull surface. To guarantee successful transcranial MRgFUS treatment without suffering these various skull issues, further technical improvements are required.ope

Regional Connectivity Changes According to Seizure Outcome of Temporal Epilepsy Surgery- A Magnetoencephalography Study

Objective: Temporal lobectomy is often successful in treatment of patients with medically intractable temporal lobe epilepsy (TLE), but prediction of its long-term outcome is of great interest. Here, we investigated usefulness of comparison analysis of pre- and post-surgical magnetoencephalopgrahy data in predicting prognosis of temporal lobectomy. Methods: The authors retrospectively analyzed pre-and post-operative MEG and presence of any seizures after temporal lobectomy in 8 patients with TLE. Spectral powers averaged from spike-free epochs in each condition (pre- and post-operation) were compared between 4 patients free from seizures and the other 4 with recurrent seizures. We also performed connectivity analysis based on phase locking values (PLVs) around resection margins of possible epileptogenic focus as regions of interest. Results: Spectral analysis on peri-lesional areas demonstrated relative increase of delta power in the patients without seizure freedom. On connectivity analysis, decrease of PLVs between other areas and temporal lobe focus after surgery were noted in patients with good surgical outcome while persistence or increase were found in patients with recurred seizures. Conclusion: This pilot study on comparison of power spectrum and connectivity metrics between pre- and post-op MEG exhibits a potential for predicting seizure outcome after TLE surgery.ope

Surgical Management of Central Neuropathic Pain Using the Neuroablative Procedures of Brain

Central pain is defined as pain initiated or caused by a primary lesion or dysfunction within the central nervous system and has proved the most difficult pain to control. Many intracranial ablative procedures have been tried, including stereotactic cingulotomy, thalamotomy, and mesencephalotomy, which have been described to be effective in about 50% to 60% although the relief of pain is faded out with time. Anterior cingulotomy is effective for the relief of cancer pain and noncancer chronic pain. Although few side effects are potential benefits of cingulotomy, the effectiveness for central pain is not yet established. Mesencephalotomy is particular value in central denervation pain, cancer pain involving the head, neck but its use is limited due to significant morbidity. The value of thalamotomy for treatment of central pain is not documented. Trigeminal tractotomy and nucleotomy are beneficial for vagoglossopharyngeal neuralgia, geniculate neuralgia, and the caudalis DREZ is beneficial for atypical facial pain, postherpetic neuralgia. Recently neurostimulation is recommended for the treatment of central pain or neuropahic pain rather than neuroablation. The use of destructive central procedures for central pain and noncancer chronic pain has not yet been well defined. With the potential benefit being less certain, priority might be given to a procedure with less risk.ope

Focused ultrasound-induced blood-brain barrier opening improves adult hippocampal neurogenesis and cognitive function in a cholinergic degeneration dementia rat model

BACKGROUND: The persistence of adult hippocampal neurogenesis (AHN) is sharply decreased in Alzheimer's disease (AD). The neuropathologies of AD include the presence of amyloid-β deposition in plaques, tau hyperphosphorylation in neurofibrillary tangles, and cholinergic system degeneration. The focused ultrasound (FUS)-mediated blood-brain barrier opening modulates tau hyperphosphorylation, the accumulation of amyloid-β proteins, and increases in AHN. However, it remains unclear whether FUS can modulate AHN in cholinergic-deficient conditions. In this study, we investigated the effect of FUS on AHN in a cholinergic degeneration rat model of dementia. METHODS: Adult male Sprague-Dawley rats (n = 48; 200-250 g) were divided into control (phosphate-buffered saline injection), 192 IgG-saporin (SAP), and SAP+FUS groups; in the two latter groups, SAP was injected bilaterally into the lateral ventricle. We applied FUS to the bilateral hippocampus with microbubbles. Immunohistochemistry, enzyme-linked immunosorbent assay, immunoblotting, 5-bromo-2'-deoxyuridine labeling, an acetylcholinesterase assay, and the Morris water maze test were performed to assess choline acetyltransferase, acetylcholinesterase activity, brain-derived neurotrophic factor expression, neural proliferation, and spatial memory, respectively. Statistical significance of differences in between groups was calculated using one-way and two-way analyses of variance followed by Tukey's multiple comparison test to determine the individual and interactive effects of FUS on immunochemistry and behavioral analysis. P < 0.05 was considered significant. RESULTS: Cholinergic degeneration in rats significantly decreased the number of choline acetyltransferase neurons (P < 0.05) in the basal forebrain, as well as AHN and spatial memory function. Rats that underwent FUS-mediated brain-blood barrier opening exhibited significant increases in brain-derived neurotrophic factor (BDNF; P < 0.05), early growth response protein 1 (EGR1) (P < 0.01), AHN (P < 0.01), and acetylcholinesterase activity in the frontal cortex (P < 0.05) and hippocampus (P < 0.01) and crossing over (P < 0.01) the platform in the Morris water maze relative to the SAP group after sonication. CONCLUSIONS: FUS treatment increased AHN and improved spatial memory. This improvement was mediated by increased hippocampal BDNF and EGR1. FUS treatment may also restore AHN and protect against neurodegeneration, providing a potentially powerful therapeutic strategy for AD.ope

Analysis of the Non-diagnostic Results after Stereotactic Biopsy

Objective: Although stereotactic brain biopsy has played an important role in the diagnosis and management of brain lesions, there is a significant number of patients in whom a histologic diagnosis is not achieved. The non-diagnostic result of stereotactic biopsy poses a management dilemma. The goal of this study was to analyze the non-diagnostic results after stereotactic biopsy, subsequent management, progress and final diagnosis. Methods: The authors reviewed the clinical and radiological records of 158 patients who underwent stereotactic brain biopsies using Leksell stereotactic frame. We included 138 patients who were followed more than 6 months in this study. Results: The results were diagnostic in 118 cases and the overall diagnostic yield of the procedure was 85.6%. A definite histological diagnosis was not made in 20 patients: gliosis in 10, normal white matter in 5, necrosis in 2, infiltration of inflammatory cell in 2, and insufficient material in 1. The subsequent managements, progress and their final diagnoses were described. Conclusion: Stereotactic biopsy has evolved as a powerful and safe tool to provide tissue diagnoses with minimal disruption of normal functioning brain. Multiple serial biopsy, intraoperative histological diagnosis, and updated imaging-guided biopsy should be tried to minimize the sampling error. Clinical and radiological follow-up are essential for further diagnosis and management in non-diagnostic cases.ope

The effect of microvascular decompression for hemifacial spasm caused by vertebrobasilar dolichoectasia

OBJECTIVE: Hemifacial spasm (HFS) caused by vertebrobasilar dolichoectasia (VBD) is very rare, and in theses cases, it is difficult to decompress the nerve from its vascular compression. The objective of this study was to investigate the outcome of microvascular decompression (MVD) for HFS caused by VBD. METHODS: There were 10 patients of HFS caused by VBD at our hospital between September 1978 and September 2008. We evaluated magnetic resonance angiography (MRA) and time of flight magnetic resonance imaginge (TOF MRI) findings using the criteria for VBD. We compared the clinical outcomes of MVD for the 10 patients with VBD with the overall outcomes of the total 2058 MVDs performed for HFS. RESULTS: The results of MVD for HFS caused by VBD were successful in 90.9% of cases. The postoperative complication rate in VBD was 45.5%. Offending vessels in patients with VBD were identified visually during surgery. Adverse effects after MVD were found in 4 patients. We found that the diameter of VBD was significantly greater in patients with complications than in those with no complications (p=0.028). CONCLUSION: Our data shows that MVD may be a good treatment modality for HFS caused by VBD but care must be taken to avoid adverse effects from the procedure. It is important to detach the dolichoectatic artery from its surrounding structures sufficiently to allow it to be easily movable. In addition, attempts should be made to lessen the retraction of the cerebellum during release of the dolichoectatic artery.ope