Thomas Czech

Extracerebral organ dysfunction and neurologic outcome after aneurysmal subarachnoid hemorrhage

OBJECTIVE To analyze the influence of extracerebral organ system dysfunction after aneurysmal subarachnoid hemorrhage (SAH) on mortality and neurologic outcome. DESIGN Observational study with retrospective data extraction. SETTING Neurosurgical intensive care unit (NICU) at a primary level university hospital, supervised and staffed by both members of the Clinic of Neurosurgery and the Clinic of Anesthesiology and General Intensive Care. PATIENTS Two hundred forty-two patients treated for intracranial aneurysm rupture within 7 days of the most recent SAH. INTERVENTIONS Routine neurosurgical interventions for obliteration of the ruptured aneurysm (microsurgery, Guglielmi Detachable Coils embolization) and for treatment of posthemorrhagic hydrocephalus (ventriculostomy, cerebrospinal fluid shunt implantation). MEASUREMENTS AND MAIN RESULTS Respiratory, renal, hepatic, cardiovascular, and hematologic organ system functions were evaluated both individually and in aggregate by using a modified version of the Multiple Organ Dysfunction (mMOD) score. Of 1,452 organ system functions assessed in 242 patients during their NICU stay, 714 organ system functions were intact (cerebral: 0, extracerebral: 714), 556 organ systems had mild-to-moderate dysfunctions (mMOD scoremax 1-2 for the affected organ system; cerebral: 153, extracerebral: 403), and 182 organ systems failed (mMOD scoremax 3 for the affected organ system; cerebral: 89, extracerebral: 93). Severity of extracerebral organ system dysfunctions correlated with the degree of neurologic impairment (Hunt and Hess [H&H] score) in a graded fashion. Similarly, the chance to develop systemic inflammatory response syndrome (SIRS) during the NICU stay increased with increasing admission H&H grade. The incidence of SIRS and septic shock was 29% and 10.3%, respectively. The mortality rate was 40.2% in patients with SIRS and 80% for patients suffering septic shock. Seventy-seven percent of extracerebral organ system failures (OSFs) occurred in conjunction with SIRS: 51% of respiratory OSFs, 97% of renal OSFs, 100% of hepatic OSFs, 96% of cardiovascular OSFs, and 73% of hematopoietic OSFs. Both CNS dysfunction and extracerebral organ system dysfunctions were significantly related to neurologic outcome. The probability of unfavorable neurologic outcome significantly increased with both decreasing cerebral perfusion pressure (CPP) and increasing severity of extracerebral organ dysfunction. CONCLUSION Aneurysmal SAH and its neurologic sequelae accounted for the principal morbidity and mortality in the current series. Development of extracerebral organ system dysfunction was associated with a higher probability of unfavorable neurologic outcome. Systemic inflammation (SIRS) and secondary organ dysfunction were the principal non-neurologic causes of death.

Immunohistochemical analysis of INI1 protein in malignant pediatric CNS tumors: Lack of INI1 in atypical teratoid/rhabdoid tumors and in a fraction of primitive neuroectodermal tumors without rhabdoid phenotype.

Immunohistochemical lack of nuclear INI1 protein expression has been recently described as characteristic finding in atypical teratoid/rhabdoid tumors (AT/RTs), and has been suggested as useful marker to distinguish AT/RTs from other malignant pediatric central nervous system (CNS) tumors. In this study, we examined a large series of malignant pediatric CNS tumors to determine the immunohistochemical expression of INI1 protein in different malignant pediatric tumor entities. Archival paraffin-embedded biopsy specimens of 289 malignant pediatric CNS tumors including medulloblastomas, supratentorial primitive neuroectodermal tumors, glioblastomas, anaplastic astrocytomas, anaplastic ependymomas, choroid plexus carcinomas, germ cell tumors, and AT/RTs were analyzed immunohistochemically for expression of nuclear INI1 protein. Positive INI1 staining was observed in 263 tumors. Lack of INI1 protein was detectable in 26 tumors. Seventeen of the 26 tumors showed morphologically characteristic features of AT/RTs, whereas 9 embryonal tumors did not display rhabdoid features. Tumors without rhabdoid phenotype but lack of INI1 showed an aggressive clinical course and poor response to conventional treatment regimens. In summary, immunohistochemical expression of INI1 protein is lacking in tumors displaying characteristic morphologic features of AT/RT. Furthermore, a certain number of embryonal tumors without rhabdoid features but lack of INI1 protein and aggressive biologic behavior can be detected. We conclude that INI1 protein analysis should be routinely performed in all malignant pediatric embryonal CNS tumors to detect cases with lack of INI1 protein, because patients with these tumors are likely to benefit from intensified treatment.

5-Aminolevulinic acid is a promising marker for detection of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement.

Because of intratumoral heterogeneity, diffusely infiltrating gliomas that lack significant contrast enhancement on magnetic resonance imaging are prone to tissue sampling error. Subsequent histologic undergrading may delay adjuvant treatments. 5‐Aminolevulinic acid (5‐ALA) leads to accumulation of fluorescent porphyrins in malignant glioma tissue, and is currently used for resection of malignant gliomas. The aim of this study was to clarify whether 5‐ALA might serve as marker for visualization of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement for precise intraoperative tissue sampling.

Evaluation of preoperative high magnetic field motor functional MRI (3 Tesla) in glioma patients by navigated electrocortical stimulation and postoperative outcome

Objectives: The validity of 3 Tesla motor functional magnetic resonance imaging (fMRI) in patients with gliomas involving the primary motor cortex was investigated by intraoperative navigated motor cortex stimulation (MCS). Methods: Twenty two patients (10 males, 12 females, mean age 39 years, range 10–65 years) underwent preoperative fMRI studies, performing motor tasks including hand, foot, and mouth movements. A recently developed high field clinical fMRI technique was used to generate pre-surgical maps of functional high risk areas defining a motor focus. Motor foci were tested for validity by intraoperative motor cortex stimulation (MCS) employing image fusion and neuronavigation. Clinical outcome was assessed using the Modified Rankin Scale. Results: FMRI motor foci were successfully detected in all patients preoperatively. In 17 of 22 patients (77.3%), a successful stimulation of the primary motor cortex was possible. All 17 correlated patients showed 100% agreement on MCS and fMRI motor focus within 10 mm. Technical problems during stimulation occurred in three patients (13.6%), no motor response was elicited in two (9.1%), and MCS induced seizures occurred in three (13.6%). Combined fMRI and MCS mapping results allowed large resections in 20 patients (91%) (gross total in nine (41%), subtotal in 11 (50%)) and biopsy in two patients (9%). Pathology revealed seven low grade and 15 high grade gliomas. Mild to moderate transient neurological deterioration occurred in six patients, and a severe hemiparesis in one. All patients recovered within 3 months (31.8% transient, 0% permanent morbidity). Conclusions: The validation of clinically optimised high magnetic field motor fMRI confirms high reliability as a preoperative and intraoperative adjunct in glioma patients selected for surgery within or adjacent to the motor cortex.

Evaluation of Cerebral Vasospasm after Early Surgical and Endovascular Treatment of Ruptured Intracranial Aneurysms

OBJECTIVE To document the influence of the treatment modality (early surgery versus early endovascular treatment) on measures of cerebral vasospasm in a nonrandomized series of 156 patients treated within 72 hours of aneurysmal subarachnoid hemorrhage. METHODS The following parameters were prospectively collected in a computerized data base and retrospectively analyzed for association with vasospasm-related ischemic infarctions: 1) Hunt and Hess (H&H) grade, 2) Fisher grade, 3) highest mean cerebral blood flow velocity (CBFVMAX) and maximum percent change in mean CBFV (%deltaCBFV) as recorded by transcranial Doppler ultrasound, 4) incidence of repeat subarachnoid hemorrhage, 5) incidence of delayed ischemic neurological deficits, 6) incidence of delayed ischemic infarctions, and 7) Glasgow Outcome Scale score. RESULTS Forty-one patients (26.3%) suffered ischemic infarctions. The ischemic infarction rate was correlated with higher H&H grade (P = 0.002), higher Fisher grade (P = 0.05), higher CBFVMAX (P < 0.001) and %deltaCBFV (P = 0.01), occurrence of repeat subarachnoid hemorrhage, occurrence of delayed ischemic neurological deficits, and endovascular treatment (P = 0.02). CONCLUSION The infarction rate was higher with endovascular treatment versus surgery (37.7 versus 21.6%), as a result of a skewed Fisher Grade 4 infarction pattern in the endovascular treatment group versus the surgery treatment group (66.7 versus 24.5%). We suspect that unremoved subarachnoid/intracerebral clots contributed to the higher infarction rate with endovascular treatment. When patients with Fisher Grade 4 and H&H Grade V were excluded from analysis, the difference in infarct incidence between the treatment groups no longer reached statistical significance (Fisher Grades 1-3, P = 0.49; H&H Grades I-IV, P = 0.96).

Chronic shunt-dependent hydrocephalus after early surgical and early endovascular treatment of ruptured intracranial aneurysms.

OBJECTIVE The goal of this study was to document the influence of the treatment method (early surgery versus early endovascular treatment) on the development of chronic shunt-dependent hydrocephalus in a series of 242 patients treated within 7 days after aneurysmal subarachnoid hemorrhage (SAH). METHODS The following parameters were prospectively recorded in a computerized database and retrospectively analyzed for association with chronic shunt-dependent hydrocephalus: 1) Hunt and Hess grade, 2) Fisher computed tomographic grade, 3) incidence of repeat SAH, 4) aneurysm location, and 5) treatment method (early surgery versus early endovascular treatment). RESULTS Forty of 187 patients (21.4%) who survived the SAH and its neurological and/or medical sequelae underwent definitive shunting for treatment of chronic hydrocephalus. The rate of shunt dependency was positively correlated with a higher Hunt and Hess grade (P < 0.001), a higher Fisher computed tomographic grade (P = 0.003), the occurrence of intraventricular hemorrhage (P < 0.001), repeat SAH (P = 0.003), and aneurysms arising at the anterior communicating artery (P < 0.001). CONCLUSION The results of the present study indicate that the treatment method used does not affect the risk of the later development of chronic shunt-dependent hydrocephalus (early surgery, 23.2% [29 of 125]; early endovascular treatment, 17.7% [11 of 62]; P = 0.45).

Ictal Scalp EEG in Unilateral Mesial Temporal Lobe Epilepsy

Summary: Purpose: We wished to determine the predictive significance of unilateral hippocampal atrophy and interictal spikes on localization of ictal scalp EEG changes and assess whether ictal EEG provides information that might change treatment or influence prognosis in patients with such characteristics of epilepsy.

Angiocentric glioma: report of clinico-pathologic and genetic findings in 8 cases.

Angiocentric glioma has recently been described as a novel epilepsy associated tumor with distinct clinico-pathologic features. We report the clinical and pathologic findings in 8 additional cases of this rare tumor type and extend its characterization by genomic profiling. Almost all patients had a history of long-standing drug-resistant epilepsy. Cortico-subcortical tumors were located in the temporal and parietal lobes. Seizures began at 3 to 14 years of age and surgery was performed at 6 to 70 years. Histologically, the tumors were characterized by diffuse growth and prominent perivascular tumor cell arrangements with features of astrocytic/ependymal differentiation, but lacking neoplastic neuronal features. Necrosis and vascular proliferation were not observed and mitoses were sparse or absent. MIB-1 proliferation indices ranged from <1% to 5%. Immunohistochemically, all cases stained positively for glial fibrillary acidic protein, vimentin, protein S100B, variably for podoplanin, and showed epithelial membrane antigen-positive cytoplasmic dots. Electron microscopy showed ependymal characteristics in 2 of 3 cases investigated. An analysis of genomic imbalances by chromosomal comparative genomic hybridization revealed loss of chromosomal bands 6q24 to q25 as the only alteration in 1 of 8 cases. In 1 of 3 cases, a high-resolution screen by array-comparative genomic hybridization identified a copy number gain of 2 adjacent clones from chromosomal band 11p11.2 containing the protein-tyrosine phosphatase receptor type J (PTPRJ) gene. All patients are seizure free and without evidence of tumor recurrence at follow-up times ranging from 1/2 to 6.9 years. Our findings support 2 previous reports proposing that angiocentric glioma is a novel glial tumor entity of low-grade malignancy.

Incidence of atypical teratoid/rhabdoid tumors in children: a population-based study by the Austrian Brain Tumor Registry, 1996-2006.

Atypical teratoid/rhabdoid tumors are highly malignant embryonal central nervous system (CNS) tumors that were defined as an entity in 1996. As compared with other malignant CNS tumors, their biological behavior is particularly aggressive, but patients may benefit from an intensified treatment. Atypical teratoid/rhabdoid tumors display a complex histomorphology, which renders them prone to misdiagnosis. They occur predominantly in young children, with an estimated prevalence of 1% to 2% among all pediatric CNS tumors. However, population‐based data on the incidence of these tumors are not yet available.

Outcome predictors for surgical treatment of temporal lobe epilepsy with hippocampal sclerosis

Purpose: To study long‐term postoperative course and identify predictors for postoperative seizure control in patients with medically intractable temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS), diagnosed by magnetic resonance imaging (MRI), and ascertained histopathologically. To compare patients becoming seizure‐free (i.e., cured from epilepsy) and patients experiencing prolonged seizure‐free periods interposed with recurring seizures.