A Combined Approach to Intracerebral Hemorrhage: Intravenous Mesenchymal Stem Cell Therapy with Minimally Invasive Hematoma Evacuation.

BACKGROUND: Mesenchymal stem cells (MSCs) are multipotent stromal cells currently being tested as therapy for a variety of diseases. MSC therapy and hematoma evacuation using a minimally invasive approach are being studied separately to improve clinical outcomes after stroke. We report the first case of a patient with intracerebral hemorrhage (ICH) treated with combination MSC therapy and endoscopic hematoma evacuation. CASE REPORT: A 36-year-old woman with a past medical history of essential chronic hypertension and right lung bronchial atresia presented to the emergency department with acute neurologic decline (National Institute of Health Stroke Scale [NIHSS] score, 22). Computed tomography showed a 4.4 × 3.5 × 3.5 cm right basal ganglia hemorrhage with intraventricular extension. An external ventricular drain was placed, and she was enrolled in a Phase I clinical trial investigating intravenous MSC therapy for acute ICH. Continued neurologic deterioration due to increased intracranial pressure led to minimally invasive hematoma evacuation using the Artemis Neuro Evacuation Device (Penumbra, Inc.) on hospital day 4. Follow-up scans showed decreased density and extent of hemorrhage. She was discharged on day 41 with improved neurologic function scores (NIHSS score, 2). At 3-month follow-up, she was walking on her own, but had residual left arm and hand weakness (modified Rankin Score, 2). CONCLUSIONS: This case report suggests that the combination of MSC therapy and minimally invasive hematoma evacuation may be safe and well tolerated. Further larger randomized clinical trials are required to identify whether MSC therapy in combination with minimally invasive hematoma evacuation is safe, tolerable, and potentially improves outcomes than either alone.

A Comparison of Motor Functional Recovery and Brain Damage between Striatal Lesions Induced by Ischemia and Hemorrhage in Rats.

BACKGROUND: The purpose of this study was to evaluate the natural recovery process and tissue injury associated with cerebral hemorrhage and cerebral infarction, which were induced to the same degree, in the striatum of rats. METHODS: Male Wistar rats were divided into intracerebral hemorrhagic (ICH) and ischemia (ISC) groups, with the ICH group injected with a collagenase solution and the ISC group injected with an endothelin-1 solution. In the SHAM group, physiological saline was injected. Motor function was evaluated by the ladder and forelimb placing tests on the first day before surgery and the first, seventh, and 14th day after surgery. On day 15 after surgery, brain tissue was harvested and frozen sections were prepared. Nissl staining was performed, and the tissue loss, ventricular, and hemispheric volumes were analyzed. RESULTS: On the first day of surgery, the ICH group had significantly decreased motor function compared with the ISC group. However, subsequent recovery of motor function was faster in the ICH group than that in the ISC group. In addition, tissue loss and hemispheric volumes were significantly higher in the ISC group than those in the ICH group, whereas the ventricular volume was significantly higher in the ICH group than that in the ISC group. CONCLUSIONS: Collectively, our findings indicate that, in ICH and ISC where the brain damage involves the same site and is approximately the same size, motor function is recovered faster in ICH than that in ISC. As such, differences in secondary degeneration are likely affected.

Traumatic basal ganglia hematomas: an analysis of 20 cases.

Twenty patients with traumatic basal ganglia hematoma (TBGH) were studied. Of the 20 patients, 16 were male and 4 were female, with an age range of 4-89 years (mean, 54.4 years). The causes of injury were traffic accidents in 12 patients and falls in 8. The mean admission GCS score was 7.5. Skull fractures were revealed in five patients (25 %). The hematoma was found in the putamen in 15 patients (80 %), the thalamus in 4, and the caudate in 1. The mean hematoma volume was 10.7 mL. The CT findings indicated focal contusions in 9 patients, subdural hematoma in 5, intraventricular hemorrhage in 4, subarachnoid hemorrhage in 10, and diffuse axonal injury in 5. Six patients (30 %) underwent surgery. The final outcomes were poor: 7 patients (35 %) died, 1 was in a vegetative state, 4 experienced severe disabilities, and 8 patients (40 %) made a favorable recovery. The statistical analysis identified the GCS score and midline shift as prognostic factors.Our study revealed interesting characteristics of TBGH, including a high frequency of putaminal involvement, a low frequency of skull fractures, a high frequency of associated intracranial lesions, and a high poor outcome and mortality rate.

Surgical treatment for large spontaneous basal ganglia hemorrhage: retrospective analysis of 253 cases.

OBJECTIVES: Spontaneous intracerebral hemorrhage (ICH) is a challenge to both neurologists and neurosurgeons. We aim to summarize the surgical treatment of ICH based on retrospective analysis of our patients. METHODS: Two hundred and fifty-three patients with spontaneous ICH from August 2008 to August 2011 were retrospectively analyzed. Clinical data, including preoperative ICH score, pre- and postoperative GCS score, hematoma volume, postoperative brain infarction, 30-day mortality, and GOS 3 months postictus, were collected. One hundred and fifty patients had their intracranial pressure (ICP) monitored, and data were recorded and analyzed. All patients underwent craniotomy and clot removal under general anesthesia. Outcome analysis was stratified using hematoma volume, ICH score, preoperative GCS score, and decompressive craniectomy (DC). RESULTS: The mean hematoma volume was 70.8 mL, and 68 patients (26.9%) underwent DC. The mean postoperative ICP was 28.8 ± 6.7 mmHg for patients without DC, and only 17.5 ± 8.6 mmHg for patients with DC. Twenty-five patients (9.9%) died within 30 days of operation, and 88 patients (34.8%, GOS ≥ 4) had good outcome 3 months after surgery. ICH volume > 50 mL, preoperative GCS score ≤ 8, and ICH score ≥ 3 are risk factors for unfavorable outcomes. CONCLUSIONS: DC can be used for patients with low preoperative GCS score, and it effectively reduces ICP and 30-day mortality. Hematoma volume, preoperative GCS score, and ICH score are of predictive value for surgical outcome of large basal ganglia hemorrhage.

Effects of minimally invasive techniques for evacuation of hematoma in basal ganglia on cortical spinal tract from patients with spontaneous hemorrhage: observed by diffusion tensor imaging.

OBJECTIVE: To observe the effect of minimally invasive removal of intracranial hematoma in basal ganglia on cortical spinal tract (CST). METHODS: Twenty-seven patients with intracerebral hemorrhage (ICH) in basal ganglia were selected and divided into a minimally invasive treatment group (13 patients) and a medical treatment group (14 patients) randomly: the volume of hematoma was 30-50 ml, with an average of 39.20 ± 4.85 ml in minimally invasive group and 38.70 ± 6.33 ml in medical treatment group. All patients underwent the whole brain diffusion tensor imaging (DTI) in 1 week after onset; fractional anistropy (FA) values of CST in internal capsule and cerebral peduncle ipsilateral and contralateral to the hematoma side in minimally invasive group were determined and then compared with those in medical treatment group. RESULTS: The minimally invasive treatment group showed that FA values of CST in internal capsule and cerebral peduncle on the affected side were 0.524 ± 0.045 and 0.534 ± 0.020, respectively, and in medical treatment group, FA values were 0.425 ± 0.050 and 0.468 ± 0.040, respectively. FA values of internal capsule and cerebral peduncle CST in minimally invasive treatment group were significantly increased as compared with the medical treatment group, and a significant difference was noted. In minimally invasive group, we obtained pre-operative DTI in five patients; FA values of CST in internal capsule and cerebral peduncle ipsilateral to the hemorrhage side were 0.428 ± 0.032 and 0.515 ± 0.048, respectively, 1 week after the hematoma was evacuated FA values of CST in internal capsule and cerebral peduncle increased significantly. Therefore, minimally invasive surgery for evacuation of intracranial hematomas could reduce the damages to CST. At the same time, the CST which was oppressed and displaced by hematoma restored to normal position largely or completely after the minimally invasive removal of intracranial hematoma. CONCLUSIONS: The changes of CST could be visualized by DTI in patients with ICH. Minimally invasive removal of intracranial hematoma could effectively reduce the injury to the CST and could restore the CST which was oppressed and displaced by the hematoma to the normal position.

Neuroprotective effect of erythropoietin and darbepoetin alfa after experimental intracerebral hemorrhage.

OBJECTIVE: Intracerebral hemorrhage (ICH) is a devastating clinical syndrome for which no truly efficacious therapy has yet been identified. In preclinical studies, erythropoietin (EPO) and its long-lasting analog, darbepoetin alfa, have been demonstrated to be neuroprotective in several models of neuronal insult. The objectives of this study were to analyze whether the systemic administration of recombinant human EPO (rHuEPO) and its long-lasting derivative darbepoetin alfa expedited functional recovery and brain damage in a rat model of ICH. METHODS: Experimental ICH was induced in rats by injecting autologous blood into the right striatum under stereotactic guidance. Subsequently, animals underwent placebo treatment, daily injections of rHuEPO, or weekly injections of darbepoetin alfa. Animals were killed 14 days after injury. RESULTS: Both rHuEPO and darbepoetin alfa were effective in reducing neurological impairment after injury, as assessed by the neurological tasks performed. rHuEPO- and darbepoetin alfa-treated animals exhibited a restricted brain injury with nearly normal parenchymal architecture. In contrast, the saline-treated group exhibited extensive cerebral cytoarchitectural disruption and edema. The number of surviving NeuN-positive neurons was significantly higher in the rats treated with rHuEPO and darbepoetin alfa compared with those that received saline (P < 0.05). CONCLUSION: These results demonstrate that weekly administered darbepoetin alfa confers behavioral and histological neuroprotection after ICH in rats similar to that of daily EPO administration. Administration of EPO and its long-lasting recombinant forms affords significant neuroprotection in an ICH model and may hold promise for future clinical applications.

Gross-total hematoma removal of hypertensive basal ganglia hemorrhages: a long-term follow-up.

BACKGROUND AND PURPOSE: Hypertensive basal ganglia hemorrhage (HBGH) accounts for 35%-44% of cases of hypertensive intracranial hemorrhage (ICH), which is one of the most devastating forms of cerebrovascular disease. In this study, intracerebral hematoma was evacuated with a burr hole craniectomy. The relationships of residue hematoma volume to brain edema, inflammation factors and the long-term prognosis of HBGH patients were studied. METHODS: One hundred and seventy-six patients with HBGH were randomly divided into gross-total removal of hematoma (GTRH) and sub-total removal of hematoma (STRH) groups. The pre-operative and post-operative data of the patients in the two groups were compared. The pre-operative data included age, sex, hematoma volume, time from the ictus to the operation, Glasgow Coma Scale (GCS) scores, and the European Stroke Scale (ESS) scores. The post-operative information included edema grade, level of thromboxane B2 (TXB2), 6-keto-prostaglandin F1a (6-K-PGF1a), tumor necrosis factor-a (TNF-a) and endothelin (ET) in hematoma drainage or cerebral spinal fluid (CSF), ESS and Barthel Index (BI). RESULTS: There was no statistical difference between the two groups (P>0.05) in the pre-operative data. The levels of TXB2, 6-K-PGF1a, TNF-a and ET in the GTRH group were significantly lower than those in the STRH group at different post-operative times. The ESS in the GTRH group increased rapidly after the operation and was higher than that in the STRH group. There was a significant difference between the two groups (P<0.05). The post-operative CT scan at different times showed that the brain edema grades were better in the GTRH group than in the STRH group. The BI was higher in the GTRH group than in the STRH group (P<0.05). CONCLUSIONS: GTRH is an effective method to decrease ICH-induced injury to brain tissue. Such effect is related to decreased perihematomal edema formation and secondary injury by coagulation end products activated inflammatory cascade.

[Comparison of curative effect and analysis of influencing factors in patients with basal ganglion hemorrhage treated with traditional craniotomy and mini-invasive operation].

OBJECTIVE: To compare the curative effect of traditional craniotomy and mini-invasive operation on basal ganglion hemorrhage, and analyze influencing factors related to the differences. METHODS: Fifty-five cases with basal ganglion hemorrhage according with the enrollment criterion of standardized treatment of hemorrhagic stroke were analyzed. Twenty-eight cases were treated with mini-invasive operation (mini-invasive group) and 27 cases with traditional craniotomy (craniotomical group). The evaluation indexes included postoperative complications, consciousness in 3 days and 2 weeks after operation, and activity of daily life (ADL) in 3 months after operation. SPSS 10.0 software was used for statistical analysis. RESULTS: Three days after operation, 19 cases and 10 cases of abnormal consciousness were in craniotomical group and mini-invasive group, respectively (P<0.01). Seventeen cases had pulmonary infection and/or organ dysfunction in craniotomical group, and 11 cases in mini-invasive group (P<0.05). Three months after operation, 5 cases were in vegetable status and 3 died in craniotomical group, accounting for 29.6%, while 3 cases were in vegetable status and 2 died in mini-invasive group, accounting for 17.8% (P<0.05). No difference in ADL was found in the two groups with an exception of cases of vegetable status and death (>0.05). CONCLUSION: mini-invasive operation makes the abnormal consciousness recover earlier, reduces complications, vegetable status and mortality and has no obvious effect on recovery of neurological function.