ALIF versus TLIF for post-discectomy syndrome.

OBJECTIVE: To evaluate whether anterior lumbar interbody fusion (ALIF) is superior to transforaminal lumbar interbody fusion (TLIF) in cases of post-discectomy syndrome (PDS). METHODS: In this retrospective study, we analyzed the consecutive results of 83 patients operated for PDS refractory to conservative treatment. A total of 46 patients underwent ALIF via a retroperitoneal approach; 37 patients underwent TLIF. Both fusion types were augmented by means of pedicle screw instrumentation. Early and delayed complications were registered within the course of hospitalization or outpatient clinical follow-up, respectively. Parameters such as patient satisfaction, current pain levels, pain medication, and change in work ability were obtained via telephone follow-up. RESULTS: Overall, 81.9% of patients were available for follow-up. Both ALIF and TLIF significantly improved back and leg pain (p < 0.01) and were described as satisfying operations by 75.8% and 73.3% of the patients, respectively. No significant difference between ALIF and TLIF results could be observed. Complications included dural tears, screw malposition, bleeding from major vessels (ALIF), abdominal wall insufficiency (ALIF), and nerve root injury (TLIF). One patient in the ALIF group and seven patients in the TLIF group required fusion extensions to adjacent levels within the observation period (observation period was 34 and 71 months, respectively). CONCLUSIONS: Both ALIF and TLIF techniques can be applied for PDS with equally good results. The technical advantages of ALIF have to be balanced with the additional morbidity and operation time owed to the additional approach. ALIF might be associated with a lower incidence of adjacent level disease compared with TLIF.

A reminder for a very rare entity: massive tongue swelling after posterior fossa surgery.

OBJECTIVE: The purpose of this study is to report a case of presumably neurogenic macroglossia that occurred after surgical trapping of a vertebral artery (VA)-posteroinferior cerebellar artery aneurysm, and to analyze its potential pathogenesis. CLINICAL PRESENTATION: A 53-year-old woman who suffered from headaches and intermittent loss of consciousness but without evidence of subarachnoid hemorrhage was admitted. Magnetic resonance imaging and angiography showed an irregular aneurysm in the fourth segment of a left dominant VA. INTERVENTION: Surgical treatment was indicated after discussion with the neuroradiology team. During surgery, in the prone position the aneurysm ruptured. The patient became hemodynamically instable. On the first postoperative day, macroglossia appeared and remained for 3 weeks until spontaneous regression. CONCLUSION: Macroglossia is a rare complication following neurosurgical procedures with very few cases reported so far. It has been attributed to the sitting position and venous flow congestion. We illustrate a case of macroglossia, which occurred following surgery in the prone position. Its etiology remains speculative, but a neurogenic explanation seems most plausible.

Role of macrophage migration inhibitory factor in primary glioblastoma multiforme cells.

Macrophage migration inhibitory factor (MIF) is a protein that is overexpressed in many tumors, such as colon and prostate cancer, melanoma, and glioblastoma multiforme (GBM). In its function as a cytokine, MIF induces angiogenesis, promotes cell cycle progression, and inhibits apoptosis. Recently, the molecular signal transduction has been specified: MIF has been found to be a ligand to the CD74/CD44-receptor complex and to activate the ERK1/2 MAPK cascade. In addition MIF binds to the chemokine receptors CXCR2 and CXCR4. This effects an integrin-dependent leukocyte arrest and mediates leukocyte chemotaxis. Recent work has described a clearer role of MIF in GBM tumor cell lines. The current study used human primary GBM cells. We show that inhibition of MIF with ISO-1, an inhibitor of the D-dopachrome tautomerase site of MIF, reduced the growth rate of primary GBM cells in a dose-dependent manner, and in addition ISO-1 increased protein expression of MIF and its receptors CD74, CXCR2, and CXCR4 in vitro but decreased expression of CD44. Furthermore, hypoxia as cell stressor increases the protein expression of MIF in primary GBM cells. These results underscore the importance of MIF in GBM and show that MIF and its receptors may be a promising target for the treatment of malignant gliomas.

Dynamic Autoregulation Testing Does Not Indicate Changes of Cerebral Blood Flow Before and After Resection of Small- and Medium-Sized Cerebral AVM.

This study tested the hypothesis that dynamic cerebral autoregulation (AR) remains intact before and after the excision of human arteriovenous malformations (AVM). In 12 patients (six female and six male; mean age, 34 years) harboring cerebral AVMs (AVM group), and 15 patients (nine female/six male; mean age, 49 years) with deep-seated lesions (e.g., small frontobasal meningiomas) approached by transsylvian dissection (control group), we continuously assessed cerebral blood flow (CBF) using a thermo-diffusion technique, and mean arterial blood pressure (MABP). AR was estimated post-hoc using correlation-coefficient autoregulatory-index (Mx) analysis. Measurements were compared according to groups (AVM/control) and times (pre/post), referred to as conditions before and after AVM resection and transsylvian dissection, respectively. All values are given as mean ± SD. The correlation index Mx was without significant difference among the study groups, indicating unimpaired autoregulatory function. Intragroup comparisons related to AVM nidus size (small- (≤3 cm) and medium-sized (3-6 cm)) did not show significant influence on autoregulation. The study shows that in patients harboring small- and medium-sized AVMs, dynamic autoregulatory function as estimated by correlation-coefficient index analysis seems to be intact in the surrounding cerebrovascular bed perioperatively.

Evidence for a predominant intrinsic sympathetic control of cerebral blood flow alterations in an animal model of cerebral arteriovenous malformation.

In terms of neurogenic cerebral blood flow (CBF) control, the activity of the sympathetic nervous system (SNS) has a regulating effect. The impact of a manipulation of both the peripheral (via the perivascular sympathetic net) and central components (via the intracortical noradrenergic terminals originating from the locus coeruleus) on CBF-and especially on hyperperfusion syndromes-is unclear. To test the specific patterns following such alterations, cortical oxygen saturation (rSO2), regional CBF (rCBF), and cortical interstitial norepinephrine (NE) concentrations were measured. Twelve weeks after either the creation of an extracranial AV fistula or sham operation, 80 male Sprague-Dawley rats underwent one of the following procedures: (1) no SNS manipulation, (2) peripheral SNS inhibition via bilateral sympathectomy, (3) central SNS inhibition via the neurotoxin DSP-4, or (4) complete SNS inhibition. Norepinephrine concentrations were lowest after complete inhibition (NE [nmol]: pre, 1.8 ± 1.2; post, 2.4 ± 1.8) and highest following peripheral inhibition (NE [nmol]: pre, 3.6 ± 1.9; post, 6.6 ± 4.4). Following fistula occlusion, rCBF (laser Doppler unit [LDU]) and rSO2 (%SO2) increases were highest after complete inhibition (pre: 204 ± 14 LDU, 34 ± 3%SO2; post: 228 ± 18 LDU, 39 ± 3%SO2) and lowest after peripheral inhibition (pre: 221 ± 18 LDU, 41 ± 2%SO2; post: 226 ± 14 LDU, 47 ± 2%SO2). Thus, a complete inhibition down-regulates SNS activity and provokes a cortical hyperperfusion condition. With this, the hitherto unknown predominant role of the intrinsic component could be demonstrated for the first time in vivo.

Early relapses in primary CNS lymphoma after response to polychemotherapy without intraventricular treatment: results of a phase II study.

BACKGROUND: A systemic and intraventricular polychemotherapy regimen (the Bonn protocol) without radiotherapy resulted in durable responses in 75% of patients <60 years with primary CNS lymphoma (PCNSL), but was complicated by a high rate of Ommaya reservoir infections. Here, the efficacy and toxicity of this regimen without intraventricular treatment was evaluated in PCNSL. PATIENTS AND METHODS: From August 2003 to November 2005, 18 patients with PCNSL <60 years (median age, 53 years) were treated in a phase II trial with a high-dose methotrexate (MTX; cycles 1, 2, 4 and 5) and cytarabine (Ara-C; cycles 3 and 6) based systemic therapy including dexamethasone, vinca-alkaloids, ifosfamide and cyclophosphamide. RESULTS: Study accrual was prematurely stopped in November 2005 due to a high rate of early relapses. Seventeen of 18 patients were assessable for response: nine (53%) achieved complete response (CR), two (12%) complete response/unconfirmed (CRu) and two (12%) partial response (PR); four (24%) showed progressive disease (PD). One treatment was stopped due to toxicity. Median follow-up was 23 months, median response duration was only 10 months in responding patients, and median time to treatment failure (TTF) was 8 months in the whole group. Median overall survival (OS) has not been reached. Systemic toxicity was mainly hematologic. CONCLUSIONS: In PCNSL patients <60 years, polychemotherapy without intraventricular treatment results in a high response rate, but is associated with early relapses in the majority of cases. This is in contrast to the results achieved with the same protocol but with intraventricular treatment.

FLAIR-/T1-/T2-co-registration for image-guided diagnostic and resective epilepsy surgery.

OBJECTIVE: For technical reasons, T2-weighted and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) sequences do not allow morphological orientation with high anatomic resolution, but they may show small epileptogenic lesions. Considering the peculiarities of diagnostic and resective epilepsy surgery the present study focused on the co-registration of various magnetic resonance sequences for guided epilepsy surgery. METHODS: Fifty patients (24 men; 26 women) aged 2 to 74 years (mean, 32 yr), in whom epileptogenic lesions were not readily identifiable on three-dimensional T1-weighted MRI scans underwent additional two-dimensional T2-weighted and FLAIR sequences before diagnostic and/or resective epilepsy surgery. FLAIR and/or T2-weighted images were co-registered to the T1-weighted data set and were displayed on the navigation station on site for guided invasive diagnostics and for resection according to an individualized resection plan. Postoperative MRI scanning was routinely performed for assessment of resection extent. RESULTS: Co-registered T1- and FLAIR-/T2-images allowed for image-guided intraoperative identification of all lesions (n = 50). Control MRI scans revealed that complete resection was performed as planned before the operation in 49 patients and incomplete resection was performed in one patient. Preliminary seizure outcome with a mean follow up of 14 months (range, 7-24 mo) was assigned according to the Engel classification: Class I, 78%; Class II, 12%; Class III, 4%; Class IV, 6%. CONCLUSION: Image guidance on the basis of image fusion/co-registration of T1- and FLAIR-/T2-images allows for intraoperative identification of otherwise poorly visible lesions on standard MRI sequences in good spatial resolution. Recall of this information during surgery from the navigation system's screen assists in achieving the goal of precise electrode placement, or complete resection of the lesion as well as of the perilesional epileptogenic tissue and improves the surgeon's intraoperative orientation.

Recurrent inactivation of the PRDM1 gene in primary central nervous system lymphoma.

Primary lymphomas of the CNS (PCNSLs) show molecular features of the late germinal center exit B-cell phenotype and are impaired in their terminal differentiation as indicated by a lack of immunoglobulin class switching. Because the positive regulatory domain I protein with ZNF domain (PRDM1/BLIMP1) is a master regulator of terminal B-cell differentiation into plasma cells, we investigated a series of 21 PCNSLs for the presence of mutations in the PRDM1 gene and alterations in the expression pattern of the PRDM1 protein. Direct sequencing of all coding exons of the PRDM1 gene identified deleterious mutations associated with abrogation of PRDM1 protein expression in 4 of 21 (19%) PCNSLs. Thus, similar to systemic diffuse large B-cell lymphomas, PRDM1 may be a tumor suppressor in some PCNSL and contribute to lymphomagenesis by impairing terminal differentiation.

Limbic event-related potentials to words and pictures in the presurgical evaluation of temporal lobe epilepsy.

We recorded limbic event-related potentials (ERPs) with intrahippocampal depth electrodes in a more demanding verbal and an easier pictorial continuous recognition task in patients undergoing presurgical evaluations of their medical refractory mesial temporal lobe epilepsies (MTLE). In all cases depth electrodes were implanted because non-invasive studies could not demonstrate unilateral seizure-onset unequivocally. For the present study we only considered 24 patients who eventually were found to suffer from unilateral MTLE, in whom hippocampal sclerosis (HS) was confirmed histologically, and who were seizure-free post-operatively. We found that the rhinal anterior medial temporal lobe N400 (AMTL-N400) to first presentations of words but not to pictures was reduced in amplitude on the side of seizure origin. Our data suggest that limbic ERPs to words are more sensitive to the epileptogenic process than those to pictures. Thus, if limbic ERPs are recorded as part of invasive presurgical evaluations, verbal instead of pictorial recognition paradigms should be employed.

Intracranially recorded memory-related potentials reveal higher posterior than anterior hippocampal involvement in verbal encoding and retrieval.

The human hippocampus is essential for both encoding and recollection, but it remains controversial whether there is a functionally different involvement of anterior versus posterior parts of the hippocampus in these memory processes. In the present study, we examined encoding and retrieval processes via intrahippocampal recordings in 27 patients with unilateral temporal lobe epilepsy. Multicontact depth electrodes were implanted along the longitudinal axis of the hippocampus as part of the presurgical evaluation. In a continuous word recognition test, subjects had to indicate whether words were new or already presented. Recognized old words, as compared to new words, resulted in a larger P600 component, as well as in a larger late negative component (LNC, 600-900 msec). In addition, subsequently remembered words elicited a larger positivity (400 to 900 msec) than later forgotten words. We found differences concerning the distribution along the hippocampus for the LNC old-new effect, reflecting successful retrieval, as well as for the subsequent memory effect, reflecting successful encoding. Both effects were larger the further posterior an electrode was located in the hippocampus. Findings are suggestive for a predominant posterior hippocampal involvement in both verbal encoding and retrieval.

Neonatal high pressure hydrocephalus is associated with elevation of pro-inflammatory cytokines IL-18 and IFNgamma in cerebrospinal fluid.

BACKGROUND: In human neonatal high pressure hydrocephalus (HPHC), diffuse white matter injury and gliosis predispose to poor neuro-developmental outcome. The underlying mechanism for diffuse white matter damage in neonatal HPHC is still unclear. Analogous to inflammatory white matter damage after neonatal hypoxemia/ischemia, we hypothesized that pro-inflammatory cytokines could be involved in neonatal HPHC. If so, early anti-inflammatory therapy could ameliorate white matter damage in HPHC, before irreversible apoptosis has occurred. In HPHC and control neonates, we therefore aimed to compare cerebrospinal fluid (CSF) concentrations of IL18, IFNgamma and sFasL (interleukin 18, interferon gamma and apoptosis marker soluble-Fas ligand, respectively). METHODS: In neonatal HPHC (n = 30) and controls (n = 15), we compared CSF concentrations of IL18, IFNgamma and sFasL using sandwich ELISA. HPHC was grouped according to etiology: spina bifida aperta (n = 20), aqueduct stenosis (n = 4), and fetal intra-cerebral haemorrhage (n = 6). Neonatal control CSF was derived from otherwise healthy neonates (n = 15), who underwent lumbar puncture for exclusion of meningitis. RESULTS: In all three HPHC groups, CSF IL18 concentrations were significantly higher than control values, and the fetal intracranial haemorrhage group was significantly higher than SBA group. Similarly, in all HPHC groups CSF-IFNgamma concentrations significantly exceeded the control group. In both HPHC and control neonates, CSF FasL concentrations remained within the range of reference values. CONCLUSION: Independent of the pathogenesis, neonatal HPHC is associated with the activation of the pro-inflammatory cytokines (IL-18 and IFNgamma) in the CSF, whereas CSF apoptosis biomarkers (sFasL) were unchanged. This suggests that anti-inflammatory treatment (in addition to shunting) could be helpful to preserve cerebral white matter.

Mumford-Shah model for one-to-one edge matching.

This paper presents a new algorithm based on the Mumford-Shah model for simultaneously detecting the edge features of two images and jointly estimating a consistent set of transformations to match them. Compared to the current asymmetric methods in the literature, this fully symmetric method allows one to determine one-to-one correspondences between the edge features of two images. The entire variational model is realized in a multiscale framework of the finite element approximation. The optimization process is guided by an estimation minimization-type algorithm and an adaptive generalized gradient flow to guarantee a fast and smooth relaxation. The algorithm is tested on T1 and T2 magnetic resonance image data to study the parameter setting. We also present promising results of four applications of the proposed algorithm: interobject monomodal registration, retinal image registration, matching digital photographs of neurosurgery with its volume data, and motion estimation for frame interpolation.

The madness of Dionysus: a neurosurgical perspective on Friedrich Nietzsche.

OBJECTIVE: To examine the possibility that an intracranial mass may have been the etiology of the headaches and neurological findings of the philosopher Friedrich Nietzsche (1844-1900) and the cause of his ultimate mental collapse in 1889. METHODS: The authors conducted a comprehensive English and German language literature search on the topic of Nietzsche's health and illness, examining Nietzsche's own writings, medical notes from his physicians, contemporary medical literature, biographical texts, and past attempts at pathography. We also examined archived portraits and engravings of the philosopher from 1864 onward. An English language search in the modern literature on the topic of psychiatric presentations of intracranial mass lesions was also conducted. RESULTS: From his late 20s onward, Nietzsche experienced severe, generally right-sided headaches. He concurrently suffered a progressive loss of vision in his right eye and developed cranial nerve findings that were documented on neurological examinations in addition to a disconjugate gaze evident in photographs. His neurological findings are consistent with a right-sided frontotemporal mass. In 1889, Nietzsche also developed a new-onset mania which was followed by a dense abulia, also consistent with a large frontal tumor. CONCLUSION: A close examination of Nietzsche's symptomatic progression and neurological signs reveals a clinical course consistent with a large, slow growing, right-sided cranial base lesion, such as a medial sphenoid wing meningioma. Aspects of his presentation seem to directly contradict the diagnosis of syphilis, which has been the standard explanation of Nietzsche's madness. The meningioma hypothesis is difficult, though not impossible, to prove; imaging studies of Nietzsche's remains could reveal the bony sequelae of such a lesion.

Expression pattern and cellular sources of chemokines in primary central nervous system lymphoma.

The expression pattern of a subset of chemokines and their corresponding receptors was investigated in primary central nervous system lymphomas (PCNSL). The tumor cells consistently expressed CXCR4, CXCL12, CXCR5, and CXCL13, both at mRNA and protein levels. Cerebral endothelial cells were positive for CXCL12 and CXCL13, while reactive astrocytes and microglial cells expressed CXCL12, CCR5, and CCR6. Inflammatory T cells in PCNSL were characterized by CCR5 and CCR6 positivity. Taken together, our data indicate a cell type-specific repertoire of chemokine and chemokine receptor expression in PCNSL suggesting that chemokine-mediated interactions facilitate crossing of the blood-brain barrier as well as intracerebral dissemination of PCNSL cells. In addition, chemokines expressed by tumor cells may contribute to induction of reactive glial changes and influence the composition of inflammatory infiltrates in PCNSL. Therefore, cell type specific expression of distinct chemokine profiles likely plays a role in the pathogenesis of PCNSL and may contribute to their characteristic histological appearance.

Hippocampal event-related potentials to tone duration deviance in a passive oddball paradigm in humans.

The mismatch negativity (MMN), a component of event-related potentials (ERPs), is assumed to reflect a preattentive auditory discrimination process. Although an involvement of hippocampal structures in deviance detection was shown in animal experiments, invasive recordings in humans have not been able to provide such an evidence so far. In the current study, ERPs were recorded from intrahippocampal and scalp electrodes in 16 epilepsy patients. Stimulation consisted of trains of six tones, with one tone deviating in duration (100 vs. 50 ms). In the rhinal cortex, ERPs elicited by deviants were larger in amplitude than those of standards (around 200 ms). The rhinal activation was succeeded by a long-lasting hippocampal ERP component (around 350 ms). However, in contrast to the rhinal activation, hippocampal activation was also elicited by the 1st stimuli of the train and might, therefore, be related more to salience detection than to deviance detection. The current study provides evidence that the MMN is part of a multistage comparison process and that the rhinal cortex is part of its underlying cortical network.

Towards a functional topography of sensory gating areas: invasive P50 recording and electrical stimulation mapping in epilepsy surgery candidates.

The filtering of sensory information, also referred to as "sensory gating", is impaired in various neuropsychiatric diseases. In the auditory domain, sensory gating is investigated mainly as a response decrease of the auditory evoked potential component P50 from one click to the second in a double-click paradigm. In order to relate deficient sensory gating to anatomy, it is essential to identify the cortical structures involved in the generation of P50. However, the exact cerebral topography of P50 gating remains largely unknown. In a group of 17 patients with drug-resistant focal epilepsy, P50 was recorded invasively via subdural electrodes, and the topography of functionally indispensable ("eloquent") cortices was obtained by electrical stimulation mapping. These eloquent areas were involved in language, motor, and sensory functions. P50 could be identified in 13 patients in either temporal (n=8) or midfrontal sites (n=5). There were six occurrences (in five patients) of overlap of sites with maximal P50 responses and eloquent areas. Those were auditory (n=1), supplementary sensorimotor (n=3), primary motor (n=1), and supplementary negative motor (n=1). Results suggest that the early stage of sensory gating already involves a top-down modulation of sensory input by frontal areas.

Transcriptional profiling of the nuclear factor-kappaB pathway identifies a subgroup of primary lymphoma of the central nervous system with low BCL10 expression.

Recent studies point to a role of nuclear factor (NF)-kappaB signaling in a subset of diffuse large B cell lymphomas. We have analyzed the expression of 21 genes encoding NF-kappaB family members, upstream modulators, and targets in 32 primary central nervous system lymphomas (PCNSLs) by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Compared with nonmalignant germinal center centroblasts, expression of BCL10, REL, IAP1, and TRAF1 was significantly lower in PCNSLs, whereas that of BAX, BCLXL, BCL2, MALT1, CARD9, CARD10, CARD11, CARD14, CCND2, cFLIP, RELA, RELB, NFKB1, NFKB2, and IRF4 was higher. Hierarchical clustering of gene expression data revealed two distinct subgroups of PCNSLs, which were characterized by significantly different transcriptional levels, predominantly of BCL10, but also of REL and IAP1. Thus, these quantitative RT-PCR data with expression of genes of the NF-kappaB family as well as NF-kappaB-regulated genes together with immunohistochemical detection of nuclear RELA and REL indicate activation of the NF-kappaB pathway in PCNSLs, which may contribute to their high proliferative activity and the low level of apoptosis.

Chromosomal translocations fusing the BCL6 gene to different partner loci are recurrent in primary central nervous system lymphoma and may be associated with aberrant somatic hypermutation or defective class switch recombination.

Primary central nervous system lymphomas (PCNSLs) are diffuse large B cell lymphomas confined to the brain. Only minimal data exist on chromosomal aberrations underlying PCNSLs. We studied 41 PCNSLs by fluorescence in situ hybridization for breakpoints affecting the BCL6 locus in chromosomal band 3q27. Of 37 cases evaluable, 14 (38%) carried a breakpoint in the BCL6 locus. Two of these showed juxtaposition of BCL6 to the IGH locus. In 4 cases, the BCL6 breakpoints were cloned using long-distance inverse polymerase chain reaction. All breakpoints were located within the BCL6 major translocation cluster. The translocation partners were the IGH gene in 14q32.33, the IGL gene in 22q11.22, and the histone 1 H4I gene in 6p22.1. In the fourth case, a deletion in 3q leads to loss of an 837-kb fragment extending from the first intron of BCL6 to the third intron of the lipoma-preferred partner (LPP) gene. This deletion may bring the BCL6 gene under the control of regulatory elements of the LPP gene or the miRNA-28 gene located in intron 4 of LPP. DNA sequence analysis of the junctional sequences provided evidence that aberrant class switch recombination or somatic hypermutation may be involved in the generation of BCL6 translocations.

Habituation of auditory evoked potentials in intracranial and extracranial recordings.

Effects of stimulus repetition are investigated in short-term habituation experiments. In these experiments, trains of stimuli are applied with longer intervals of no stimulation between the trains. In scalp recordings, an amplitude and latency decrease of the auditory N100 is usually observed at the beginning of the train. This contrasts to a recent finding with intracranial recordings, exhibiting an effect on N100 amplitude, but not on its latency. In the current study, P50 and N100 were simultaneously recorded intra- and extracranially in epilepsy patients. The amplitudes of P50 and N100 decreased in both recordings, whereas the P50 latency was not significantly affected. A latency decrease was revealed for the extracranially recorded N100, but not for the intracranial N100. This dissociation between the intracranial and scalp recordings might be explained by a different sensitivity of the two measurements for N100 generators.