Precision Capsular Infarct Modeling to Produce Hand Motor Deficits in Cynomolgus Macaques

Stroke research in non-human primates (NHPs) with gyrencephalic brains is a critical step in overcoming the translational barrier that limits the development of new pharmaceutical and rehabilitative strategies for stroke. White-matter stroke (WMS) has a unique pathophysiology from graymatter stroke and is not well understood because of a lack of pertinent animal models. To create a precise capsular infarct model in the cynomolgus macaque, we first used electrical stimulation to map hand movements, followed by viral tracing of the hand motor fibers (hMFs). This enabled us to identify stereotactic targets in the posterior limb of the internal capsule (PLIC). Neural tracing showed that hMFs occupy the full width of the PLIC, owing to overlap with the motor fibers for the leg. Furthermore, the hMFs were distributed in an oblique shape, requiring coronal tilting of the target probe. We used the photothrombotic infarct lesioning technique to precisely destroy the hMFs within the internal capsule. Double-point infarct lesioning that fully compromised the hMFs resulted in persistent hand motor and walking deficits whereas single-point lesioning did not. Minor deviations in targeting failed to produce persistent motor deficits. Accurate stereotactic targeting with thorough involvement of motor fibers is critical for the production of a capsular infarct model with persistent motor deficits. In conclusion, the precision capsular infarct model can be translated to the NHP system to show persistent motor deficits and may be useful to investigate the mechanism of post-stroke recovery as well as to develop new therapeutic strategies for the WMS.

Three-axis Modification of Coordinates Enables Accurate Stereotactic Targeting in Non-human Primate Brains of Different Sizes

The brain grows with age in non-human primates (NHPs). Therefore, atlas-based stereotactic coordinates cannot be used directly to target subcortical structures if the size of the animal's brain differs from that used in the stereotactic atlas. Furthermore, growth is non-uniform across different cortical regions, making it difficult to simply apply a single brain-expansion ratio. We determined the skull reference lines that best reflect changes in brain size along the X, Y, and Z axes and plotted the changes in reference-line length against the changes in body weight. The skull reference lines had a linear relationship with body weight. However, comparison of skull reference lines with body weight confirmed the non-uniform skull growth during postnatal development, with skull growth more prominent in the X and Y axes than the Z axis. Comparing the differences between the atlas-based lengths and those calculated empirically from plot-based linear fits, we created craniometric indices that can be used to modify stereotactic coordinates along all axes. We verified the accuracy of the corrected stereotactic targeting by infusing dye into internal capsule in euthanized and preserved NHP brains. Our axis-specific, craniometric-index-adjusted stereotactic targeting enabled us to correct for targeting errors arising from differences in brain size. Histological verification showed that the method was accurate to within 1 mm. Craniometric index-adjusted targeting is a simple and relatively accurate method that can be used for NHP stereotactic surgery in the general laboratory, without the need for high-resolution imaging.

An Experimental Infarct Targeting the Internal Capsule: Histopathological and Ultrastructural Changes

BACKGROUND: Stroke involving the cerebral white matter (WM) has increased in prevalence, but most experimental studies have focused on ischemic injury of the gray matter. This study was performed to investigate the WM in a unique rat model of photothrombotic infarct targeting the posterior limb of internal capsule (PLIC), focusing on the identification of the most vulnerable structure in WM by ischemic injury, subsequent glial reaction to the injury, and the fundamental histopathologic feature causing different neurologic outcomes. METHODS: Light microscopy with immunohistochemical stains and electron microscopic examinations of the lesion were performed between 3 hours and 21 days post-ischemic injury. RESULTS: Initial pathological change develops in myelinated axon, concomitantly with reactive change of astrocytes. The first pathology to present is nodular loosening to separate the myelin sheath with axonal wrinkling. Subsequent pathologies include rupture of the myelin sheath with extrusion of axonal organelles, progressive necrosis, oligodendrocyte degeneration and death, and reactive gliosis. Increase of glial fibrillary acidic protein (GFAP) immunoreactivity is an early event in the ischemic lesion. WM pathologies result in motor dysfunction. Motor function recovery after the infarct was correlated to the extent of PLIC injury proper rather than the infarct volume. CONCLUSIONS: Pathologic changes indicate that the cerebral WM, independent of cortical neurons, is highly vulnerable to the effects of focal ischemia, among which myelin sheath is first damaged. Early increase of GFAP immunoreactivity indicates that astrocyte response initially begins with myelinated axonal injury, and supports the biologic role related to WM injury or plasticity. The reaction of astrocytes in the experimental model might be important for the study of pathogenesis and treatment of the WM stroke.

Nonoperative interventions for spinal pain

Spinal pain is a common symptom that motivates visiting a physician. However, the natural course is usually benign and few patients need invasive treatment. Even though history taking, neurological examination, and imaging studies provide useful information for understanding the etiology of spinal pain, the pain chart is the most important tool for decision making regarding spinal interventions. Invasive treatments for chronic spinal pain refractory to conservative management include surgery as well as established interventions such as medial branch blocks, nerve root blocks, the sacroiliac joint block, and radiofrequency neurotomy, as well as emerging procedures such as pressure-controlled discography and percutaneous epidural adhesiolysis. Surgery should be considered for patients with a progressive neurologic deficit including significant radiculopathy, failure of spinal interventions, or an uncertain or serious diagnosis.

Vertebral Distraction during Anterior Cervical Discectomy and Fusion Causes Postoperative Neck Pain

OBJECTIVE: Vertebral distraction is routinely performed during anterior cervical discectomy and fusion (ACDF). Overdistraction can injure the facet joints and may cause postoperative neck pain consequently. The purpose of this study was to investigate the clinical relevance of distraction force during ACDF. METHODS: This study included 24 consecutive patients with single level cervical disc disease undergoing single level ACDF. We measure the maximum torque just before the the arm of the Caspar retractor was suspended by the rachet mechanism by turning the lever on the movable arm using a torque meter. In order to turn the lever using the torque driver, we made a linear groove on the top of the lever. We compared the neck disability index (NDI) and visual analogue scale (VAS) scores between the high torque group (distraction force>6 kgf.cm) and the low torque group (distraction force< or =6 kgf.cm) at routine postoperative intervals of 1, 3, 5 days and 1, 3, 6 months. RESULTS: The VAS scores for posterior neck pain had a linear correlation with torque at postoperative 1st and 3rd days (y=0.99x-1.1, r2=0.82; y=0.77x-0.63, r2=0.73, respectively). VAS scores for posterior neck pain were lower in the low torque group than in the high torque group on both 1 and 3 days postoperatively (3.1+/-1.3, 2.6+/-1.0 compared with 6.0+/-0.6, 4.9+/-0.8, p<0.01). However, the difference in NDI scores was not statistically significant in all postoperative periods. CONCLUSION: Vertebral distraction may cause posterior neck pain in the immediate postoperative days. We recommend not to distract the intervertebral disc space excessively with a force of more than 6.0 kgf.cm.

Finite Element Analysis of the Biomechanical Effect of Coflex(TM) on the Lumbar Spine

OBJECTIVE: The biomechanical properties of the Coflex(TM) (Paradigm Spine, NY, USA), a device designed to provide dynamic stabilization without lumbar fusion, have not been clearly defined. The purpose of this study was to determine the efficacy and biomechanical effect of Coflex(TM) using finite element model (FEM). METHODS: A 3D geometric model of the L3-L5 was created by integrating computerized tomography (CT) images. Based on the geometric model, a 3D FEM was created and the Coflex(TM) model was incorporated into the base model. Mechanical load dependent on the postural changes and boundary conditions, were imposed to simulate various 3D physiological states. The simulation analysis included stress and strain distributions, intervertebral disc deformation, and the range of motion of the facet joint and lumbar spinous process. RESULTS: Coflex(TM) significantly restrained displacement in extension, lateral bending and compression of joint between the L4-5 as one in the experimental group was observed -1.3% of flexion, -24.5% of extension, -44.5% of lateral bending and -37.2%. The average intradiscal pressure of the L4-5 decreased by 63% and the average facet contract force of the L4-5 decreased markedly by 34% in the experimental group. A load of 120 MPa from extension was observed at the base of spinous process in the experimental group. CONCLUSION: The Coflex(TM) can be safely used for achieving functional dynamic stabilization of the lumbar vertebral column while preserving the intactness of the other components. However, the fatigue fracture of the L4 spinous process should be carefully monitored.

Effect of Bone Cement Volume and Stiffness on Occurrences of Adjacent Vertebral Fractures after Vertebroplasty

OBJECTIVE: The purpose of this study is to find the optimal stiffness and volume of bone cement and their biomechanical effects on the adjacent vertebrae to determine a better strategy for conducting vertebroplasty. METHODS: A three-dimensional finite-element model of a functional spinal unit was developed using computed tomography scans of a normal motion segment, comprising the T11, T12 and L1 vertebrae. Volumes of bone cement, with appropriate mechanical properties, were inserted into the trabecular core of the T12 vertebra. Parametric studies were done by varying the volume and stiffness of the bone cement. RESULTS: When the bone cement filling volume reached 30% of the volume of a vertebral body, the level of stiffness was restored to that of normal bone, and when higher bone cement exceeded 30% of the volume, the result was stiffness in excess of that of normal bone. When the bone cement volume was varied, local stress in the bony structures (cortical shell, trabecular bone and endplate) of each vertebra monotonically increased. Low-modulus bone cement has the effect of reducing strain in the augmented body, but only in cases of relatively high volumes of bone cement (>50%). Furthermore, varying the stiffness of bone cement has a negligible effect on the stress distribution of vertebral bodies. CONCLUSION: The volume of cement was considered to be the most important determinant in endplate fracture. Changing the stiffness of bone cement has a negligible effect on the stress distribution of vertebral bodies.

The Effect of Electric Cortical Stimulation after Focal Traumatic Brain Injury in Rats

OBJECTIVE: To evaluate the effects of electric cortical stimulation in the experimentally induced focal traumatic brain injury (TBI) rat model on motor recovery and plasticity of the injured brain. METHOD: Twenty male Sprague-Dawley rats were pre-trained on a single pellet reaching task (SPRT) and on a Rotarod task (RRT) for 14 days. Then, the TBI model was induced by a weight drop device (40 g in weight, 25 cm in height) on the dominant motor cortex, and the electrode was implanted over the perilesional cortical surface. All rats were divided into two groups as follows: Electrical stimulation (ES) group with anodal continuous stimulation (50 Hz and 194 micros duration) or Sham-operated control (SOC) group with no electrical stimulation. The rats were trained SPRT and RRT for 14 days for rehabilitation and measured Garcia's neurologic examination. Histopathological and immunostaining evaluations were performed after the experiment. RESULTS: There were no differences in the slice number in the histological analysis. Garcia's neurologic scores & SPRT were significantly increased in the ES group (p<0.05), yet, there was no difference in RRT in both groups. The ES group showed more expression of c-Fos around the brain injured area than the SOC group. CONCLUSION: Electric cortical stimulation with rehabilitation is considered to be one of the trial methods for motor recovery in TBI. However, more studies should be conducted for the TBI model in order to establish better stimulation methods.

A Case of Angiocentric Glioma with Unusual Clinical and Radiological Features

Angiocentric glioma was recently recognized as a distinct clinicopathological entity in the 2007 World Health Organization classification of tumors of the central nervous system. Typically, it presents with seizure in children and young adults. However, our patient did not have a history of seizure. Seizure did not occur up to 6 months after operation. Although it usually does not have calcification brain magnetic resonance imaging in our patient showed T1-hyperintense and T2-hypointense signals with calcification.

Stem Cell Dynamics in an Experimental Model of Stroke / 전남의대학술지

We investigated the migration of endogenous neural stem cells (NSCs) toward an infarct lesion in a photo-thrombotic stroke model. The lesions produced by using rose bengal dye (20 mg/kg) with cold light in the motor cortex of Sprague-Dawley rats were also evaluated with sequential magnetic resonance imaging (MRI) from 30 minutes through 8 weeks. Migration of NSCs was identified by immunohistochemistry for nestin monoclonal antibody in the lesion cortex, subventricular zone (SVZ), and corpus callosum (CC). The contrast to noncontrast ratio (CNR) on MRI was greatest at 12 hours in DWI and decreased over time. By contrast, T1-weighted and T2-weighted images showed a constant CNR from the beginning through 8 weeks. MRI of the lesional cortex correlated with histopathologic findings, which could be divided into three stages: acute (edema and necrosis) within 24 hours, subacute (acute and chronic inflammatory cell infiltration) at 2 to 7 days, and chronic (gliofibrosis) at 2 to 4 weeks. The volume of the infarct was significantly reduced by reparative gliofibrosis. The number of nestin+ NSCs in the contralateral SVZ was similar to that of the ipsilateral SVZ in each group. However, the number of nestin+ NSCs in the ipsilateral cortex and CC increased at 12 hours to 3 days compared with the contralateral side (p<0.01) and was reduced significantly by 7 days (p<0.01). Active emigration of internal NSCs from the SVZ toward the infarct lesion may also contribute to decreased volume of the infarct lesion, but the self-repair mechanism by endogenous NSCs is insufficient to treat stroke causing extensive neuronal death. Further studies should be focused on amplification technologies of NSCs to enhance the collection of endogenous or transplanted NSCs for the treatment of stroke.

Stem Cell Dynamics in an Experimental Model of Stroke / 전남의대학술지

We investigated the migration of endogenous neural stem cells (NSCs) toward an infarct lesion in a photo-thrombotic stroke model. The lesions produced by using rose bengal dye (20 mg/kg) with cold light in the motor cortex of Sprague-Dawley rats were also evaluated with sequential magnetic resonance imaging (MRI) from 30 minutes through 8 weeks. Migration of NSCs was identified by immunohistochemistry for nestin monoclonal antibody in the lesion cortex, subventricular zone (SVZ), and corpus callosum (CC). The contrast to noncontrast ratio (CNR) on MRI was greatest at 12 hours in DWI and decreased over time. By contrast, T1-weighted and T2-weighted images showed a constant CNR from the beginning through 8 weeks. MRI of the lesional cortex correlated with histopathologic findings, which could be divided into three stages: acute (edema and necrosis) within 24 hours, subacute (acute and chronic inflammatory cell infiltration) at 2 to 7 days, and chronic (gliofibrosis) at 2 to 4 weeks. The volume of the infarct was significantly reduced by reparative gliofibrosis. The number of nestin+ NSCs in the contralateral SVZ was similar to that of the ipsilateral SVZ in each group. However, the number of nestin+ NSCs in the ipsilateral cortex and CC increased at 12 hours to 3 days compared with the contralateral side (p<0.01) and was reduced significantly by 7 days (p<0.01). Active emigration of internal NSCs from the SVZ toward the infarct lesion may also contribute to decreased volume of the infarct lesion, but the self-repair mechanism by endogenous NSCs is insufficient to treat stroke causing extensive neuronal death. Further studies should be focused on amplification technologies of NSCs to enhance the collection of endogenous or transplanted NSCs for the treatment of stroke.

Anesthetic management of percutaneous balloon compression of the trigeminal ganglion for the treatment of trigeminal neuralgia: Two cases report / 대한마취과학회지

Trigeminal neuralgia is sudden, usually unilateral, severe brief stabbing recurrent pain in the distribution of one or more branches of the 5th cranial nerve. Treatments of trigeminal neuralgia include systemic trials of medications and surgical procedures such as microvascular decompression, stereotactic radiosurgery, percutaneous glycerol or alcohol rhizolysis, percutaneous radiofrequency rhizotomy, and percutaneous balloon compression (PBC). PBC of the trigeminal ganglion using a balloon catheter was introduced by Mullan and Lichtor in 1983. Since then, many papers have been published describing results of this technique. Typically, this procedure is performed under general anesthesia. However, little is known about the use of PBC for the treatment of trigeminal neuralgia in Korea. We report here our anesthetic management of percutaneous balloon compression of trigeminal ganglion for the treatment of the trigeminal neuralgia by total intravenous anesthesia.

Clinical and Radiological Findings of Discogenic Low Back Pain Confirmed by Automated Pressure-Controlled Discography

OBJECTIVE: Few studies on the clinical spectrum of automated pressure-controlled discography (APCD)-defined positive discs have been reported to date. Thus, the present study was undertaken to analyze clinical parameters critical for diagnosis of discogenic pain and to correlate imaging findings with intradiscal pressures and pain responses in patients with APCD-positive discs. METHODS: Twenty-three patients who showed APCD-positive discs were selected for analysis. CT discogram findings and the degrees of nuclear degeneration seen on MRI were analyzed in comparison to changes of intradiscal pressure that provoked pain responses; and clinical pain patterns and dynamic factors were evaluated in relation to pain provocation. RESULTS: Low back pain (LBP), usually centralized, with diffuse leg pain was the most frequently reported pattern of pain in these patients. Overall, LBP was most commonly induced by sitting posture, however, standing was highly correlated with L5/S1 disc lesions (p < 0.01). MRI abnormalities were statistically correlated with grading of CT discogram results (p < 0.05); with most pain response observed in CT discogram Grades 3 and 4. Pain-provoking pressure was not statistically correlated with MRI grading. However, it was higher in Grade 3 than Grade 4. CONCLUSION: APCD-positive discs were demonstrated in patients reporting centralized low back pain with diffuse leg pain, aggravated by sitting and standing. MRI was helpful to assess the degree of nuclear degeneration, yet it could not guarantee exact localization of the painful discs. APCD was considered to be more useful than conventional discography for diagnosis of discogenic pain.

Effect of Cerebral Motor Cortex Stimulation in Amyotrophic Lateral Sclerosis Model: A Preliminary Controlled Study

OBJECTIVE: To observe the effect of the depolarizing stimulation in amyotrophic lateral sclerosis (ALS) mouse model on the survival and behavioral performance. METHOD: Transgenic male mouse model of ALS at the age of 9~11 weeks were divided into sham control group (n=10) and stimulation group (n=9). Electrode was implanted in the motor cortex in left hemisphere. Movement thresholds (MT) were regularly checked. Half threshold of MT, unipolar, and continuous electrical stimulation (frequency, 50 Hz; pulse duration, 220micron s) was delivered through implanted electrode. Behavioral tests including Rota-rod and Paw-grip endurance were checked every day. RESULTS: Induction of symptom was delayed in 8 days in stimulation than sham control group. However, there was no significant difference in survival in both groups. Behavioral tests showed that stimulation group is significantly better than sham group in Rota-rod (11~15 weeks) and in grip endurance (11~14, 16 weeks). MT was always between 1.0 volt and 3.2 volt in sham group, however, MT was between 0.8 volt and 2.8 volt in stimulation group. MT was jumped up around the time of death in both groups. CONCLUSION: Electrical stimulation is considered to be one of possible trial methods in ALS model. However, parameters of the stimulation in the experiment should be modified for better results.

Automated Pressure-Controlled Discography with Constant Injection Speed and Real-Time Pressure Measurement

OBJECTIVE: This study was designed to investigate automated pressure-controlled discography (APCD) findings, to calculate the elastance of intervertebral discs, and to assess the relationship between the calculated elastance and disc degeneration. METHODS: APCD was performed in 19 patients. There were a total of 49 intervertebral discs treated. Following intradiscal puncture, a dye was constantly injected and the intradiscal pressure was continuously measured. The elastance of the intervertebral disc was defined as unit change in intradiscal pressure per fractional change in injected dye volume. Disc degeneration was graded using a modified Dallas discogram scale. RESULTS: The mean elastance was 43.0 +/- 9.6 psi/mL in Grade 0, 39.5 +/- 8.3 psi/mL in Grade 1, 30.5 +/- 22.3 psi/mL in Grade 2, 30.5 +/- 22.3 psi/mL in Grade 3, 13.2 +/- 8.3 psi/mL in Grade 4 and 6.9 +/- 3.8 psi/mL in Grade 5. The elastance showed significant negative correlation with the degree of degeneration (R2 = 0.529, p = 0.000). CONCLUSION: APCD liberates the examiner from the data acquisition process during discography. This will likely improve the quality of data and the reliability of discography. Elastance could be used as an indicator of disc degeneration.

Clinical Relevance of Pain Patterns in Osteoporotic Vertebral Compression Fractures

Few studies have been conducted to explain the pain patterns resulting from osteoporotic vertebral compression fractures (OVCF). We analyzed pain patterns to elucidate the pain mechanism and to provide initial guide for the management of OVCFs. Sixty-four patients underwent percutaneous vertebroplasty (N=55) or kyphoplasty (N=9). Three pain patterns were formulized to classify pains due to OVCFs: midline paravertebral (Type A), diffuse paravertebral (Type B), and remote lumbosacral pains (Type C). The degree of compression was measured using scale of deformity index, kyphosis rate, and kyphosis angle. Numerical rating scores were serially measured to determine the postoperative outcomes. As vertebral body height (VBH) decreased, paravertebral pain became more enlarged and extended anteriorly (p<0.05). Type A and B patterns significantly showed the reverse relationship with deformity index (p<0.05), yet Type C pattern was not affected by deformity index. Postoperative pain severity was significantly improved (p<0.05), and patients with a limited pain distribution showed a more favorable outcome (p<0.05). The improvement was closely related with the restoration of VBH, but not with kyphosis rate or angle. Thus, pain pattern study is useful not only as a guide in decision making for the management of patients with OVCF, but also in predicting the treatment outcome.

Lumbo-iliac Fixation Using Modified Galveston Technique in a Patient with Metastatic Sacral Tumor

Lumbo-sacral junction is a transition zone between the mobile lumbar spine and immobile pelvis. Lumbosacral junction has been considered to be the most troublesome portion of the spine to be fused because of the difference in anatomical and biomechanical factors between spine and pelvis. A metastatic sacral tumor in a 57-year-old man was resected, followed by unilateral lumbo-iliac fixation across lumbosacral junction using modified Galveston technique. Rigid fixation was successfully achieved. Detailed anatomy and surgical techniques are presented.

Usefulness of Pain Distribution Pattern Assessment in Decision-Making for the Patients with Lumbar Zygapophyseal and Sacroiliac Joint Arthropathy

There are currently no initial guides for the diagnosis of somatic referred pain of lumbar zygapophyseal joint (LZJ) or sacroiliac joint (SIJ). We developed a classification system of LZJ and SIJ pain, the "pain distribution pattern template (PDPT)" depending on the pain distribution patterns from a pool of 200 patients whose spinal pain source was confirmed. We prospectively applied the PDPT to determine its contribution to clinical decision-making for 419 patients whose pain was presumed to arise from the LZJs (259 patients) or SIJs (160 patients). Forty-nine percent (128/259) of LZJ and 46% (74/160) of SIJ arthopathies diagnosed by PDPT were confirmed by nerve blocks. Diagnostic reliabilities were significantly higher in Type A and C patterns in LZJ and Type C in SIJ arthropathies, 64%, 80%, and 68.4%, respectively. For both LZJ and SIJ arthropathies, favorable outcome after radiofrequency (RF) neurotomies was similar to the rate of positive responses to diagnostic blocks in Type A to Type D, whereas the outcome was unpredictable in those with undetermined type (Type E). Considering the paucity of currently available diagnostic methods for LZJ and SIJ arthropathies, PDPT is useful in clinical decision- making as well as in predicting the treatment outcome.

Causes and Diagnostic Strategies for Chronic Low Back Pain

Chronic low back pain (CLBP) has become more prominent with globally increasing life expectancy. Its cause is more attributable to degenerative changes than to traumatic lesions. Although the diagnosis of CLBP is recently on higher demand, lack of clinical features and non-informative imaging findings in patients with CLBP are challenging to clinicians to establish the diagnosis. Therefore, understanding of the new concept of pathogenesis, elimination of prejudice, and evidence-based diagnostic steps are required to resolve the question of pain source. Analysis of pain distribution patterns and careful history taking can be utilized as an initial guide to divide CLBP into somatic and radicular pain. Zygapophyseal joint pain and sacroiliac joint pain representing somatic pain can be further investigated using medial branch and sacroiliac joint blocks. However, comparative blocks are essential to decreased false positive rate. Infiltration of a small volume of local anesthetics can increase the specificity of the procedures. Discogenic pain stemming from internal disk derangement can be confirmed by pressure-controlled discography. Automated discography is recommended to provide the constant rate of dye injection with obviating the fluctuation of intradiscal pressure. Evidencebased concept and diagnostic procedures can provide more accurate and efficient methods to establish the diagnosis of CLBP.

Familial Idiopathic Basal Ganglia Calcification

Familial idiopathic basal ganglia calcification(FIBGC) is an inheritable neurological condition characterized by calcium deposits in the basal ganglia and extra-basal ganglia areas. The condition manifests as parkinsonism and other variable neuropsychiatric symptoms. FIBGC is a rare condition, and its pathophysiology has not yet been fully elucidated. Here we report the results of a clinical study of two related patients diagnosed with FIBGC.