A Stereotactic Device for Intraparenchymal Spinal Cord Injections: Latest Developments for Practical Clinical Use.

This manuscript introduces the latest generation of a patient-mounted platform designed for segmental injections of therapeutics direct into the spinal cord parenchyma. It emphasizes its importance and it presents the rationale for developing this delivery methodology. It compares the newest with the previous generations, detailing how the modifications can streamline transportation, assembly, sterilization, and utilization of the platform by different surgeons. Finally, the illustrations depict the main alterations, as well as a cadaveric assessment of the device prototype in the cervical and thoracolumbar regions.

Frameless Stereotactic Targeting of the Cerebellar Dentate Nucleus in Nonhuman Primates: Translatable Model for the Surgical Delivery of Gene Therapy.

BACKGROUND: Stereotactic targeting techniques in nonhuman primate (NHP) models are often utilized in the preclinical investigation of new drug therapies with the goal of demonstrating accurate and reliable delivery of a therapy to the target tissue. However, targeting certain neuroanatomical structures can be challenging. The deep cerebellar nuclei, specifically the dentate nucleus, are potential stereotactic targets for the treatment of certain ataxias. Currently, there are no detailed techniques describing frameless targeting of these structures in a NHP model. A well-defined, accurate, and reliable stereotactic surgical approach to the dentate in these animal models is critical to prove the feasibility and safety of drug delivery in order to develop clinical protocols. METHODS: Frameless stereotactic neuronavigation was employed to target the bilateral dentate nuclei of the cerebellum in four healthy juvenile Cynomolgus monkeys via a suboccipital, transcerebellar approach. The precision and accuracy of the targeting were evaluated radiologically and histologically. RESULTS: Using the described surgical methodology, we were successful in hitting the target deep cerebellar nuclei seven out of eight times. CONCLUSION: Frameless stereotactic targeting of the cerebellar dentate nuclei in NHPs for future investigational drug delivery is feasible, safe, and accurate as described by this report. Potential areas for improving the technique are discussed.

Endoscopic third ventriculostomy versus shunt for pediatric hydrocephalus: a systematic literature review and meta-analysis.

BACKGROUND: Optimized management of pediatric hydrocephalus remains the subject of debate. Ventriculoperitoneal shunt is largely considered the standard of care. However, the advancements and introduction of new cerebrospinal fluid (CSF) diversion approaches including the use of endoscopic third ventriculostomy (ETV) offer appealing alternatives that have been reported in numerous observational series. OBJECTIVE: To evaluate the comparative safety and efficacy of shunting and ETV in pediatric hydrocephalus cases. METHODS: This systematic literature review was performed according to the PRISMA guidelines. Eligible studies were identified through a search of PubMed (Medline) and Cochrane until October 2018. A random effects model meta-analysis was conducted and the I-square was used to assess heterogeneity. The ROBINS-1 tool and Cochrane tool were used to assess risk of bias in the observational and randomized studies, respectively. RESULTS: Fourteen studies including 8419 patients were identified. Patients in the ETV group had a statistically significant lower risk of infection compared to shunt (OR: 0.19; 95% CI: 0.07-0.53; I2: 0%). All-cause mortality (OR: 0.77; 95% CI: 0.35-1.68; I2: 0%), post-operative CSF leak (OR: 1.53; 95% CI: 0.37-6.31; I2: 0%), and reoperation rates were similar between the two study groups (OR: 0.72; 95% CI: 0.39-1.32; I2: 93.5%). Subgroup analyses for re-operation demonstrated that ETV in Africa (OR: 0.13; 95% CI: 0.03-0.48; I2: 0%) and Europe (OR: 0.39; 95% CI: 0.30-0.52; I2:1.4%) was associated with significantly lower odds of re-operation compared to shunt, but not in USA/Canada (OR: 1.49; 95% CI: 0.85-2.63; I2:86.2%). Meta-regression analyses of age and duration of follow-up did not affect re-operation rates. CONCLUSIONS: ETV was associated with a statistically significant lower risk of procedure-related infection compared to shunt. All-cause mortality, CSF leak, and re-operation rates were similar between the study groups. Subgroup analysis based on the geographic region showed that ETV is associated with statistically significant lower odds for re-operation in Europe and Africa, but not in USA/Canada. Future RCTs are needed to validate the results of this study and elucidate the cause of this heterogeneity.

Elbow flexion in neonatal brachial plexus palsy: a meta-analysis of graft versus transfer.

BACKGROUND: Functional elbow flexion recovery is one of the main goals of neonatal brachial plexus palsy (NBPP) reconstruction. The current neurosurgical treatment options include nerve grafting and nerve transfer. OBJECTIVE: The present study sought to examine the literature for comparison of functional elbow flexion recovery in NBPP following nerve grafting or nerve transfer. We conducted a systematic literature review and meta-analysis according to PRISMA guidelines. A search was conducted on Pubmed/Medline and Cochrane for eligible studies published until November of 2018. Odd ratios (OR) and 95% confidence intervals (CI) were calculated to compare functional elbow flexion outcomes between nerve graft and nerve transfer. A random effects model meta-analysis was conducted. A Medical Research Council (MRC) score ≥ 3 or Active Movement Scale (AMS) ≥ 5 was considered a functional recovery of elbow flexion. RESULTS: The present study included 194 patients from 1990 to 2015 across five observational trials. Only pediatric patients with obstetric brachial plexus injury were included. The mean patient age at surgery varied between studies from 5.7 months to 11.9 months and mean follow-up from 12 to 70 months. No complications or cases of donor site morbidity were reported. From the included studies, 118 patients were reported with MRC or AMS scoring usable for odd ratio comparison. Functional recovery occurred with nerve transfer in 95.2% of patients (n = 59/62) and with nerve grafting in 96.4% of patients (n = 54/56). Overall, the outcomes for elbow flexion between the groups appeared similar (OR 1.15, 95% CI 0.19-7.08, I2 2.9%). CONCLUSION: Comparing nerve grafting and nerve transfer for NBPP, there is no statistically significant difference in functional elbow flexion recovery.

Thrombelastography does not predict clinical response to rtPA for acute ischemic stroke.

Thrombelastography (TEG) measures coagulation in venous blood. We hypothesized that TEG, by reflecting clot subtype and ex vivo fibrinolysis, might predict fibrinolytic response to tPA as reflected by rapid clinical improvement or hemorrhagic transformation of the infarct. 171 acute ischemic stroke patients treated with tPA were prospectively enrolled. Venous blood for TEG was drawn before and 10 min after tPA bolus. We measured rapid clinical improvement (RCI = 8 point improvement on NIHSS or total NIHSS of 0, 1 at 36 h), Hemorrhagic transformation (HT = any blood on imaging within 36 h), and hyperdense middle cerebral artery sign (HDMCA = biomarker for erythrocyte-rich clot). Multivariable regression models compared TEG parameters after adjusting for potential confounders. No differences in pre- or post-tPA TEG were found between patients with or without RCI. Also, there was no correlation between TEG and HDMCA. Clotting was slightly prolonged in patients with HT (p = 0.046). We failed to find a robust association between TEG and clinical response to tPA. It is likely that arterial clot lysis is determined by factors unrelated to coagulation status as measured by TEG in the venous circulation. It is unlikely that TEG will be useful to predict clinical response to tPA, but may help predict bleeding.

Thrombelastography detects possible coagulation disturbance in patients with intracerebral hemorrhage with hematoma enlargement.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) has high morbidity, and hematoma enlargement (HE) causes worse outcome. Thrombelastography (TEG) measures the dynamics of clot formation and dissolution, and might be useful for assessing bleeding risk. We used TEG to detect changes in clotting in patients with and without HE after ICH. METHODS: This prospective study included 64 patients with spontaneous ICH admitted from 2009 to 2013. TEG was performed within 6 hours of symptom onset and after 36 hours. Brain imaging was obtained at baseline and at 36±12 hours, and HE was defined as total volume increase>6 cc or >33%. TEG was also obtained from 57 controls. RESULTS: Compared with controls, patients with ICH demonstrated faster and stronger clot formation; shorter R and delta (P<0.0001) at baseline; and higher MA and G (P<0.0001) at 36 hours; 11 patients had HE. After controlling for potential confounders, baseline K and delta were longer in HE+ compared with HE- patients, indicating that HE+ patients had slower clot formation (P<0.05). TEG was not different between HE+ and HE- patients at 36 hours. CONCLUSIONS: TEG may detect important coagulation changes in patients with ICH. Clotting may be faster and stronger in immediate response to ICH, and a less robust response may be associated with HE. These findings deserve further investigation.

Iodinated contrast does not alter clotting dynamics in acute ischemic stroke as measured by thromboelastography.

BACKGROUND AND PURPOSE: Iodinated contrast agents used for computed tomography angiography (CTA) may alter fibrin fiber characteristics and decrease fibrinolysis by tissue plasminogen activator (tPA). Thromboelastography (TEG) measures the dynamics of coagulation and correlates with thrombolysis in acute ischemic stroke patients. We hypothesized that receiving CTA before tPA will not impair thrombolysis as measured by TEG. METHODS: Acute ischemic stroke patients receiving 0.9 mg/kg tPA <4.5 hours of symptom onset were prospectively enrolled. For CTA, 350 mg/dL of iohexol or 320 mg/dL of iodixanol at a dose of 2.2 mL/kg was administered. TEG was measured before tPA and 10 minutes after tPA bolus. CTA timing was left to the discretion of the treating physician. RESULTS: Of 136 acute ischemic stroke patients who received tPA, 47 had CTA before tPA bolus, and 42 had either CTA after tPA and post-tPA TEG draw or no CTA (noncontrast group). Median change in clot lysis (LY30) after tPA was 95.3% in the contrast group versus 95.0% in the noncontrast group (P=0.74). Thus, tPA-induced thrombolysis did not differ between contrast and noncontrast groups. Additionally, there was no effect of contrast on any pre-tPA TEG value. CONCLUSIONS: Our data do not support an effect of iodinated contrast agents on clot formation or tPA activity.

Lentiviral Vector Induced Modeling of High-Grade Spinal Cord Glioma in Minipigs.

BACKGROUND: Prior studies have applied driver mutations targeting the RTK/RAS/PI3K and p53 pathways to induce the formation of high-grade gliomas in rodent models. In the present study, we report the production of a high-grade spinal cord glioma model in pigs using lentiviral gene transfer. METHODS: Six Gottingen Minipigs received thoracolumbar (T14-L1) lateral white matter injections of a combination of lentiviral vectors, expressing platelet-derived growth factor beta (PDGF-B), constitutive HRAS, and shRNA-p53 respectively. All animals received injection of control vectors into the contralateral cord. Animals underwent baseline and endpoint magnetic resonance imaging (MRI) and were evaluated daily for clinical deficits. Hematoxylin and eosin (H&E) and immunohistochemical analysis was conducted. Data are presented using descriptive statistics including relative frequencies, mean, standard deviation, and range. RESULTS: 100% of animals (n = 6/6) developed clinical motor deficits ipsilateral to the oncogenic lentiviral injections by a three-week endpoint. MRI scans at endpoint demonstrated contrast enhancing mass lesions at the site of oncogenic lentiviral injection and not at the site of control injections. Immunohistochemistry demonstrated positive staining for GFAP, Olig2, and a high Ki-67 proliferative index. Histopathologic features demonstrate consistent and reproducible growth of a high-grade glioma in all animals. CONCLUSIONS: Lentiviral gene transfer represents a feasible pathway to glioma modeling in higher order species. The present model is the first lentiviral vector induced pig model of high-grade spinal cord glioma and may potentially be used in preclinical therapeutic development programs.

The dopamine response in the nucleus accumbens core-shell border differs from that in the core and shell during operant ethanol self-administration.

BACKGROUND: Ethanol self-administration has been shown to increase dopamine in the nucleus accumbens; however, dopamine levels in the accumbal subregions (core, shell, and core-shell border) have not yet been measured separately in this paradigm. This study was designed to determine if dopamine responses during operant ethanol self-administration are similar in the core, core-shell border, and shell, particularly during transfer from the home cage to the operant chamber and during consumption of the drinking solution. METHODS: Six groups of male Long-Evans rats were trained to lever-press for either 10% sucrose (10S) or 10% sucrose + 10% ethanol (10S10E) (with a guide cannula above the core, core-shell border, or shell of the accumbens). On experiment day, 5-minute microdialysis samples were collected from the core, core-shell border, or shell before, during, and after drinking. Dopamine and ethanol concentrations were analyzed in these samples. RESULTS: A significant increase in dopamine occurred during transfer of the rats from the home cage into the operant chamber in all 6 groups, with those trained to drink 10S10E exhibiting a significantly higher increase than those trained to drink 10S in the core and shell. No significant increases were observed during drinking of either solution in the core or shell. A significant increase in dopamine was observed during consumption of ethanol in the core-shell border. CONCLUSIONS: We conclude that dopamine responses to operant ethanol self-administration are subregion specific. After operant training, accumbal dopamine responses in the core and shell occur when cues that predict ethanol availability are presented and not when the reinforcer is consumed. However, core-shell border dopamine responses occur at the time of the cue and consumption of the reinforcer.

Comparative safety and efficacy of percutaneous approaches for the treatment of trigeminal neuralgia: A systematic review and meta-analysis.

Percutaneous treatments for trigeminal neuralgia (TN) include glycerol rhizotomy (GR), radiofrequency thermocoagulation (RF), and balloon compression (BC), which aim to provide pain relief by targeted injury to the trigeminal nerve pain fibers. All three techniques are well established and can provide immediate pain relief; however each of them can be associated with a range of complications. Our objective was to compare the safety and efficacy of GR, RF and BC in patients with TN. This study was performed according to the PRISMA guidelines. A random effects model meta-analysis was conducted. Fourteen studies were included. The comparisons of RF vs GR comprised 2,518 patients overall. RF was associated with statistically significant higher odds of immediate pain relief (OR: 2.65; 95% CI: 1.29-5.44; I 2:85.5%) when compared to GR. Patients in the RF group had a statistically significant higher risk of anesthesia in the trigeminal distribution (OR: 4.73; 95% CI: 2.25-9.96; I2:0%) and lower risk for herpes eruption (OR: 0.30; 95% CI: 0.17-0.56; I2 :0%). The comparison of BC vs GR included 961 patients. Patients in the BC group had a statistically significant higher risk of mastication weakness (OR: 9.29; 95% CI: 2.71-31.86; I2:0%) and diplopia due to CN IV or CN V palsy (OR: 6.31; 95% CI: 1.70-23.33; I2 :0%) compared to patients in the GR group. The comparisons of BC vs RF comprised 3,183 patients and did not show significant differences between the two groups. RF is associated with statistically significant higher odds for immediate pain relief and anesthesia and lower risk for post-operative herpes eruption as compared to GR. Patients in the BC group had a statistically significant higher risk to develop post-operative mastication weakness and diplopia when compared to GR.

Combined Radial to Axillary and Spinal Accessory Nerve (SAN) to Suprascapular Nerve (SSN) Transfers May Confer Superior Shoulder Abduction Compared with Single SA to SSN Transfer.

BACKGROUND: The restoration of shoulder function after brachial plexus injury is a high priority. Shoulder abduction and stabilization can be achieved by nerve transfer procedures including spinal accessory nerve (SAN) to suprascapular nerve (SSN) and radial to axillary nerve transfer. The objective of this study is to compare functional outcomes after SAN to SSN transfer versus the combined radial to axillary and SA to SSN transfer. METHODS: This retrospective chart review included 14 consecutive patients with brachial plexus injury who underwent SAN to SSN transfer, 4 of whom had both SA to SSN and radial to axillary nerve transfer. RESULTS: SAN to SSN transfer achieved successful shoulder abduction (≥M3) in 64.3% of this cohort (9/14). During the long-term follow-up, patients achieved an average increase of 67.5° in shoulder abduction. There was no association between motor recovery and time from injury to surgery, age, body mass index (BMI), sex, or smoking status. The 4 patients who had SAN to SSN combined with radial to axillary nerve transfer demonstrated a statistically significant increase in the range of abduction (median, 90° vs. 42.5°, respectively; P = 0.022) compared with those who had SAN to SSN transfer alone; however, the difference in Medical Research Council (MRC) grades (MRC > M3) did not reach statistical significance (P = 0.07). CONCLUSIONS: Patients with brachial plexus injury and an intact C7 root could benefit from radial to axillary transfer in addition to SAN to SSN transfer. There was no association between recovery of shoulder abduction and time interval from injury to surgery, age, sex, smoking, and BMI.

Double Fascicular Nerve Transfer to Musculocutaneous Branches for Restoration of Elbow Flexion in Brachial Plexus Injury.

Background Restriction of elbow flexion significantly limits upper extremity function following brachial plexus injuries. In recent years, the double fascicular nerve transfer procedure utilizing ulnar and median nerve transfer to musculocutaneous branches has shown promising functional outcomes. Objective To evaluate restoration of elbow flexion following a double fascicular transfer in patients with brachial plexus injuries and identify predictors of poor outcomes. Methods This retrospective review included 10 consecutive patients with brachial plexus injuries involving C5-C6 root avulsions who underwent the double nerve transfer procedure. The mean follow-up was 12 months and the primary outcome was assessment of elbow flexion with the use of the Medical Research Council (MRC) scale. Results This procedure achieved elbow flexion of MRC grade M3 or higher in 50% of our cohort. Time interval from injury to surgery showed a statistically significant inverse association with functional recovery (r = -0.73, p = 0.016). Patients who had the surgery within six months of the injury, demonstrated higher MRC grades during the follow-up (p = 0.048). There was no association between elbow flexion recovery and age, body mass index (BMI), gender, hypertension, diabetes or smoking status. Conclusions The double fascicular transfer to musculocutaneous may be a safe and effective treatment for restoration of elbow flexion. The procedure is associated with superior functional outcomes when performed within the first six months from the injury.

Survival and failure trends of cerebrospinal fluid shunts with distal slit valves: comparative study and literature review.

OBJECTIVE: The malfunction rates of and trends in various cerebrospinal fluid (CSF) shunt designs have been widely studied, but one area that has received little attention is the comparison of the peritoneal distal slit valve (DSV) shunt to other conventional valve (CV) type shunts. The literature that does exist comes from older case series that provide only indirect comparisons, and the conclusions are mixed. Here, the authors provide a direct comparison of the overall survival and failure trends of DSV shunts to those of other valve type shunts. METHODS: Three hundred seventy-two new CSF shunts were placed in pediatric patients at the authors' institution between January 2011 and December 2015. Only ventriculoperitoneal (VP) shunts were eligible for study inclusion. Ventriculoatrial, lumboperitoneal, cystoperitoneal, subdural-peritoneal, and spinal shunts were all excluded. Rates and patterns of shunt malfunction were compared, and survival curves were generated. Patterns of failure were categorized as proximal failure, distal failure, simultaneous proximal and distal (proximal+distal) failure, removal for infection, externalization for abdominal pseudocyst, and addition of a ventricular catheter for loculated hydrocephalus. RESULTS: A total of 232 VP shunts were included in the final analysis, 115 DSV shunts and 117 CV shunts. There was no difference in the overall failure rate or time to failure between the two groups, and the follow-up period was statistically similar between the groups. The DSV group had a failure rate of 54% and a mean time to failure of 17.8 months. The CV group had a failure rate of 50% (p = 0.50) and a mean time to failure of 18.5 months (p = 0.56). The overall shunt survival curves for these two groups were similar; however, the location of failure was significantly different between the two groups. Shunts with DSVs had proportionately more distal failures than the CV group (34% vs 14%, respectively, p = 0.009). DSV shunts were also found to have proximal+distal catheter occlusions more frequently than CV shunts (23% vs 5%, respectively, p = 0.005). CV shunts were found to have significantly more proximal failures than the DSV shunts (53% vs 27%, p = 0.028). However, the only failure type that carried a statistically significant adjusted hazard ratio in a multivariate analysis was proximal+distal catheter obstruction (CV vs DSV shunt: HR 0.21, 95% CI 0.05-0.81). CONCLUSIONS: There appears to be a difference in the location of catheter obstruction leading to the malfunction of shunts with DSVs compared to shunts with CVs; however, overall shunt survival is similar between the two. These failure types are also affected by other factors such etiology of hydrocephalus and endoscope use. The implications of these findings are unclear, and this topic warrants further investigation.

Chronic encapsulated intraventricular hematoma in a pediatric patient: case report.

Chronic encapsulated intraventricular hematoma (CEIVH) is a rare, intraventricular, nonneoplastic mass lesion that can become symptomatic from mass effect or obstructive hydrocephalus. Only 5 cases have been reported in the literature, and only one of these occurred in a pediatric patient and dates back to the pre-modern neuroimaging and pre-microsurgical era of neurosurgery. Imaging features can mimic those of many more common intraventricular lesions, such as choroid plexus tumors or cavernous malformations. In all reported symptomatic cases, resection was safely performed and led to a cure and symptom resolution. Here, the authors present a case of CEIVH in a pediatric patient, describe the operative techniques of resection, review the available literature, and discuss current understanding of the pathophysiology, making this the most comprehensive report on this disease entity to date. The case is a 14-year-old boy who presented with headaches and emesis. Computed tomography showed a hyperdense mass in the trigone of the right lateral ventricle. Magnetic resonance imaging showed a contrast-enhancing well-circumscribed mass. Right temporal craniotomy utilizing a posterior middle temporal gyrus transcortical approach was performed, and gross-total resection was achieved. Pathology revealed a CEIVH. The boy's postoperative course was uncomplicated, and he was discharged 2 days after surgery.

Clinical evaluation and surveillance imaging of children with myelomeningocele and shunted hydrocephalus: a follow-up study.

OBJECTIVEThe majority of children with myelomeningocele undergo implantation of CSF shunts. The efficacy of adding surveillance imaging to clinical evaluation during routine follow-up as a means to minimize the hazard associated with future shunt failure has not been thoroughly studied.METHODSA total of 300 spina bifida clinic visits during the calendar years between 2012 and 2016 were selected for this study (defined as the index clinic visit). Each index visit was preceded by a 6-month period during which no shunt evaluation of any kind was performed. At the index clinic visit, all patients were evaluated by a neurosurgeon. Seventy-four patients underwent previously scheduled surveillance CT or shunt series scans in addition to clinical evaluation (surveillance imaging group), and 226 patients did not undergo surveillance imaging (clinical evaluation group). Subsequent unexpected events, defined as emergency department visits, caregiver-requested clinic visits, and shunt revision surgeries were reviewed. The timing and likelihood of an unexpected event in each of the 2 groups were compared using Cox proportional hazard survival analysis. The rate of shunt revision surgery in the follow-up period as well as the associated outcomes and rate of complications were analyzed.RESULTSThe clinical characteristics of the 2 groups were similar. In the clinical evaluation group, 4 of 226 (1.8%) patients underwent shunt revision based on clinical findings during the index visit, compared to 8 of 74 (10.8%) patients in the surveillance imaging group who underwent shunt revision based on clinical and imaging findings at that visit (p < 0.05). In the subsequent follow-up period, there were 74 unexpected events resulting in 10 shunt revisions in the clinical evaluation group, for an event rate of 33% and operation rate of 13.5%. In the surveillance imaging group there were 23 unexpected events resulting in 2 shunt revisions, for an event rate of 34.8% and an operation rate of 8.7%; neither difference was statistically significant. The complication rate for shunt revision surgery was also not different between the groups.CONCLUSIONSObtaining predecided, routine surveillance imaging in children with myelomeningocele and shunted hydrocephalus resulted in more shunt revisions in asymptomatic patients. For patients who had negative results on surveillance imaging, the rate of shunt revision in the follow-up period was not significantly decreased compared to patients who underwent clinical examination only at the index visit.

Unusual cause of encephalopathy after brain surgery.

For patients who have had a recent neurosurgical procedure, a visit to the emergency department for encephalopathy may automatically prompt a neurosurgical consult. We present a case of a patient with a history of Chiari malformation decompressed 6 months prior who presented with a 2-week history of slowly progressive altered mental status, headache and imbalance-symptoms consistent with her initial Chiari symptoms, so neurosurgery was consulted. Imaging showed no acute abnormality, but laboratory results revealed metabolic acidosis with high salicylate levels. When reporting medication use, this patient initially left out that she had been taking Goody's powder (845 mg aspirin) for headaches, and long-term use led to metabolic encephalopathy. Despite a recent history of surgery, it is important to keep the differential diagnosis broad especially when there are signs of metabolic derangement.

Thromboelastography in patients with acute ischemic stroke.

BACKGROUND: Thromboelastography measures the dynamics of coagulation. There are limited data about thromboelastography in acute ischemic stroke other than a single study from 1974 suggesting that acute ischemic stroke patients are hypercoagulable. There have been no studies of thromboelastography in the thrombolytic era despite its potential usefulness as a measure of clot lysis. This study was designed to provide initial thromboelastography data in stroke patients before and after tissue plasminogen activator therapy and to provide the necessary preliminary data for further study of thromboelastography's ability to identify clot subtype and predict response to tissue plasminogen activator therapy. METHODS: All acute ischemic stroke patients presenting between 11/2009 and 2/2011 eligible for tissue plasminogen activator therapy were screened and 56 enrolled. Blood was drawn before (52 patients) and 10 mins after tissue plasminogen activator bolus (30 patients). Demographics, vitals, labs, 24 h National Institutes of Health Stroke Scale, and computed tomography scan results were collected. Patients were compared with normal controls. RESULTS: Acute ischemic stroke patients had shorter R (4.8 ± 1.5 vs. 6.0 ± 1.7 min, P = 0.0004), greater α Angle (65.0 ± 7.6 vs. 61.5 ± 5.9°, P = 0.01), and shorter K (1.7 ± 0.7 vs. 2.1 ± 0.7 min, P = 0.002) indicating faster clotting. Additionally, a subset formed clots with stronger platelet-fibrin matrices. Treatment with tissue plasminogen activator resulted in reduction in all indices of clot strength (LY30 = 0 (0-0.4) vs. 94.4 (15.2-95.3) P < 0.0001); however, there was considerable variability in response. CONCLUSIONS: Thromboelastography demonstrates that many acute ischemic stroke patients are hypercoaguable. Thromboelastography values reflect variable clot subtype and response to tissue plasminogen activator. Further study based on these data will determine if thromboelastography is useful for measuring the dynamic aspects of clot formation and monitoring lytic therapy.

Clot Strength as Measured by Thrombelastography Correlates with Platelet Reactivity in Stroke Patients.

OBJECTIVE: Platelet reactivity may be important in the management of patients with stroke. However, degree of platelet reactivity has not been correlated with Thrombelastography (TEG(®)) parameters in stroke. We sought to detect a correlation between TEG(®) values and clot platelet reactivity in ex vivo clots of stroke patients. METHODS: We collected venous blood from 40 patients with stroke. TEG(®) measurements were carried out and residual clots were fixed in 10% formalin immediately following completion of TEG(®). The formalin specimens were embedded in paraffin blocks, cut at 4 micrometers, and stained with CD 61 (immunohistochemical stain used to detect platelets) with appropriate controls. Under light microscopy, three pathologists blinded to TEG(®) results independently graded CD61 intensity (how aggregated/intense the CD61 stained) into a low and high group, as a proposed measurement representing the platelet reactivity of the clot. We compared pre-tPA-TEG(®) values among groups with different CD 61 intensities. RESULTS: After adjusting for confounding factors, we found statistically significant correlation between CD61 staining and several TEG(®) parameters (Delta and CD61 staining intensity (p=0.047); Angle and CD61 staining intensity grade (p=0.04); and G and CD61 staining intensity grade (p=0.04)). CONCLUSIONS: Clot strength on TEG(®) as measured by Delta, Angle, and G correlates with a clot with greater platelet reactivity.