GFAP and S100B are biomarkers of traumatic brain injury: an observational cohort study.

BACKGROUND: Biomarker levels in blood after traumatic brain injury (TBI) may offer diagnostic and prognostic tools in addition to clinical indices. This study aims to validate glial fibrillary acidic protein (GFAP) and S100B concentrations in blood as outcome predictors of TBI using cutoff levels of 1.5 µg/L for GFAP and 1.13 µg/L for S100B from a previous study. METHODS: In 79 patients with TBI (Glasgow Coma Scale score [GCS] ≤12), serum, taken at hospital admission, was analyzed for GFAP and S100B. Data collected included injury mechanism, age, gender, mass lesion on CT, GCS, pupillary reactions, Injury Severity Score (ISS), presence of hypoxia, and hypotension. Outcome was assessed, using the Glasgow Outcome Scale Extended (dichotomized in death vs alive and unfavorable vs favorable), 6 months post injury. RESULTS: In patients who died compared to alive patients, median serum levels were increased: GFAP 33.4-fold and S100B 2.1-fold. In unfavorable compared to favorable outcome, GFAP was increased 19.8-fold and S100B 2.1-fold. Univariate logistic regression analysis revealed that mass lesion, GFAP, absent pupils, age, and ISS, but not GCS, hypotension, or hypoxia, predicted death and unfavorable outcome. Multivariable analysis showed that models containing mass lesion, pupils, GFAP, and S100B were the strongest in predicting death and unfavorable outcome. S100B was the strongest single predictor of unfavorable outcome with 100% discrimination. CONCLUSION: This study confirms that GFAP and S100B levels in serum are adjuncts to the assessment of brain damage after TBI and may enhance prognostication when combined with clinical variables.

The development of a screening instrument to select patients at risk of residual complaints after lumbar disc surgery.

AIM: A considerable number of patients who undergo surgery for a lumbosacral radicular syndrome (LRS) continue to experience disability, pain, and loss of work capacity. The goal of the study is to develop a brief screening instrument to identify these patients at risk of residual complaints. METHODS: In a prospective study of 277 patients, the predictors for the outcomes disability, pain, and loss of work capacity were investigated. The best predictive model was constructed using a stepwise selection procedure (forward selection), which calculates the discriminative power of the model. Based on the relationship between regression coefficients, a clinical prediction rule was derived that predicted the probability of residual complaints after surgery for LRS. RESULTS: At 6 month follow-up 141 patients (51%) had residual complaints. The discriminative power of the instrument was .78 (AUC). The "Nijmegen Outcome of Lumbar Disc surgery Screening-instrument" (NOLDS) was based on the variables "lower education level", "younger age", "pain 3 days postoperatively", "passive pain coping", and "fear of movement/(re)injury". CONCLUSION: The results of the study are promising, showing that a brief clinical screening instrument can be used to identify patients at risk of residual complaints at 6 months after surgery for LRS. The early identification of patients at risk having residual complaints may make it possible to start tailored treatment early in the rehabilitation process.

Overview of the clinical applications of vagus nerve stimulation.

Vagus nerve stimulation (VNS) has become an established therapy for difficult-to-treat epilepsy during the past 20 years. The vagus nerve provides a unique entrance to the brain. Electrical stimulation of this structure in the cervical region allows direct modulative access to subcortical brain areas, requiring only minimally invasive surgery with low risks involved. VNS therapy has shown to reduce epileptic seizures both in number and severity in a group of patients not responding to antiepileptic drugs. The effects are accompanied by an atypical set of central side effects. After the success of the VNS therapy with epilepsy, the technique has been applied to a wide variety of disorders, ranging from major depressive disorder to Alzheimer's disease. The results of several of these are promising. In this review, the results as well as the rationale for the different applications of VNS are discussed.

Minimally invasive placement of epidural plate electrodes under local anaesthesia in spinal cord stimulation.

In the treatment of pain syndromes of different aetiologies a change has occurred from destructive interventions to stimulation procedures. Spinal cord stimulation is the best known example of this treatment strategy. It is used often in patients with persistent neuropathic pain syndromes in an extremity, for instance following low back surgery. This treatment is most frequently performed by a percutaneous placement of a single electrode, with the aid of a specially designed Tuohy needle to reach the epidural space. In cases where, for different reasons, a larger, plate electrode is needed, this has to be placed surgically by a small laminectomy. The general anaesthesia mostly needed for this procedure prevents trial stimulation necessary to check the correct electrode position. Besides this, the laminectomy procedure can subsequently result in new pain complaints due to the invasiveness of the procedure. To solve both problems we have modified the implantation technique. By using a tubular retractor system (METRx system, Medtronic Sofamor Danek, Memphis, TN), originally developed for minimally invasive degenerative disc surgery, it is possible to reach the epidural spinal space and introduce the plate electrode with a small approach under local anaesthesia both allowing trial stimulation and avoiding severe postoperative backache related to the approach in these patients.

Increased GFAP and S100beta but not NSE serum levels after subarachnoid haemorrhage are associated with clinical severity.

Assessment of initial disease severity after subarachnoid haemorrhage (SAH) remains difficult. The objective of the study is to identify biochemical markers of brain damage in peripheral blood after SAH. Hospital admission S100beta, glial fibrillary acidic protein (GFAP) and neuron-specific enolase (NSE) serum levels were analysed in 67 patients with SAH. Disease severity was determined by using the World Federation of Neurological Surgeons (WFNS) scale and the Fisher CT (computerized tomography) grading scale. Mean astroglial serum concentrations taken at hospital admission were increased (S100beta 2.8-fold and GFAP 1.8-fold) compared with the upper limit of normal laboratory reference values (P95). The mean NSE concentration was within normal limits. S100beta (P < 0.001) and GFAP (P =0.011) but not NSE levels were higher in patients who were in coma at the time of hospital admission compared with patients who were not. Similarly S100beta and GFAP but not NSE serum levels increased with higher WFNS scores, raised intracranial pressure and higher CT Fisher grade scores. Concerning the location of the aneurysm, S100beta and GFAP serum levels were within normal limits after a perimesencephalic type of haemorrhage and significantly increased after aneurysmal type SAH. Increased glial (S100beta and GFAP) but not neuronal (NSE) protein serum concentrations are found after SAH, associated to the clinical severity of the initial injury.

Dumbbell trigeminal schwannoma in a child: complete removal by a one-stage pterional surgical approach.

OBJECTIVE: The objective was to describe a rare case of a trigeminal schwannoma in a child and the surgical procedure performed for therapy. PATIENT AND METHODS: A 6-year-old girl presented with tiredness, dysarthric speech and cerebellar symptoms. Imaging studies revealed a unilateral dumbbell-shaped tumour, extending into both the middle and posterior fossa, centred over Meckel's cave. One-stage surgery was performed by pterional craniotomy. The tumour was first debulked in the middle fossa, then peeled from the wall of the cavernous sinus, followed by extirpation of the tumour from the posterior fossa. The tumour extended to the caudal cranial nerves and was completely removed. Trigeminal fascicles were distributed throughout the tumour. Histopathological examination revealed a schwannoma. CONCLUSION: Trigeminal schwannoma is a tumour that occurs rarely in childhood. Although several, often multistaged surgical strategies have been reported in the literature, this tumour was eradicated by a one-stage pterional approach.

Glial and neuronal proteins in serum predict outcome after severe traumatic brain injury.

OBJECTIVE: To study the ability of glial (glial fibrillary acidic protein [GFAP] and S100b) and neuronal (neuron specific enolase [NSE]) protein levels in peripheral blood to predict outcome after severe traumatic brain injury. METHODS: Eighty-five patients with severe traumatic brain injury (admission Glasgow Coma Score [GCS] < or = 8) were included. Blood samples taken at the time of hospital admission were analyzed for S100b, GFAP, and NSE. Data collected included demographic and clinical variables. Outcome was assessed using the Glasgow Outcome Scale (GOS) at 6 months post injury. RESULTS: The median serum levels of S100b, GFAP, and NSE were raised 18.3 fold (S100b), 4.6 fold (GFAP), and twofold (NSE) compared to normal reference values. S100b, GFAP, and NSE serum levels correlated significantly with the injury severity score and CT findings but not with age, sex, or GCS. S100b, GFAP, and NSE levels were significantly higher in patients who died or had a poor outcome 6 months post injury than in those who were alive or had good outcome. S100b level >1.13 microg/L was the strongest predictor of death with 100% discrimination, but GFAP (>1.5 microg/L) and NSE (>21.7 microg/L) levels also strongly predicted death (adjusted odds ratios 5.82 [for GFAP] and 3.91 [for NSE]). S100b, GFAP, and NSE all strongly predicted poor outcome (adjusted odds ratios 5.12 [S100b], 8.82 [GFAP], and 3.95 [NSE]). CONCLUSIONS: These results suggest that determination of serum levels of glial and neuronal proteins may add to the clinical assessment of the primary damage and prediction of outcome after severe traumatic brain injury.

The use of a head-mounted display for visualization in neuroendoscopy.

OBJECTIVE: To evaluate the clinical use of a head-mounted display (HMD) for visualization in all neuroendoscopic procedures. MATERIALS AND METHODS: We retrospectively evaluated all endoscopic and endoscope-controlled procedures in which the HMD was used in our department between July 1999 and June 2002. RESULTS: A total of 269 endoscopic procedures were performed. In 147 cases intraventricular endoscopic procedures were carried out, mostly third ventriculocisternostomies, for which a fiberscope was used exclusively. Thirty intracranial cysts were fenestrated or removed (colloid cysts) with the help of various endoscopes. A total of 87 endoscopic transsphenoidal surgeries were performed with a lensscope. In only one case was it necessary to abandon use of the HMD due to inferior visualization; in all other cases visualization by the HMD was thought to be sufficient. Fatigue of the surgeon due to wearing the helmet did not occur. All surgeons had the impression that visual strain was decreased in comparison to looking at a monitor from a distance. The working position was considered to be more comfortable when wearing the HMD, and eye-hand coordination was improved. No technical problems occurred with the system. CONCLUSIONS: The HMD is a new visualization tool in neurosurgery that may improve the ergonomics of neuroendoscopic and endoscope-controlled procedures.

Frontal ataxia in childhood.

Frontal ataxia may be the result of a unilateral frontal lesion. In this report three cases are presented with ataxia due to right frontal lesions. One case concerns a boy presenting with an unsteady gait and titubation of the trunk, mimicking developmental disequilibrium and with complex partial seizures. It proved to be caused by a small right-sided cavernoma in the middle frontal gyrus. After surgical intervention the symptoms and the seizures disappeared. Two subsequent cases concern teenage patients presenting with headache after an ENT infection and on physical examination mild dysmetric function of the upper limbs and slight disequilibrium, due to right-sided frontal lobe abscesses. After neurosurgical and antibiotic therapy the symptoms were relieved. The frontal origin of ataxia should be considered in children presenting with a "cerebellar syndrome". Frontal gait disorders consist of a clinical pattern of different gait disorders. The syndrome has been mentioned in the literature under different names. Our patients show signs compatible with the term frontal disequilibrium, a clinical pattern of frontal gait disorder. This assumes walking problems characterized by loss of control of motor planning, leading to imbalance. Remarkably, frontal ataxia may mimic developmental delay as demonstrated in the first case and may be the leading mild symptom in extensive frontal lobe damage as demonstrated by the two other cases. We suppose that frontal ataxia is the result of a disturbance in the cerebellar-frontal circuitries and an impairment of executive and planning functions of the basal ganglia-frontal lobe circuitry.

Serum- and CSF-concentrations of brain specific proteins in hydrocephalus.

OBJECT: Hydrocephalus is characterised by elevated intracranial pressure (ICP) and gives rise to brain damage. The aim of this study was to investigate the significance of brain specific proteins as markers in the evaluation of brain damage in hydrocephalus. Therefore we determined the levels of four brain specific proteins in cerebrospinal fluid (CSF) and serum of symptomatic hydrocephalic patients. METHODS: During 41 CSF shunt-operations (both primarily placed shunts and shunt-revisions) CSF and blood samples were obtained and analysed for neuron-specific enolase (NSE), S-100b, glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP). The results were compared with an age-matched control group. Patients with varying clinical symptoms, denoting different levels of increased intracranial pressure prior to surgery, were included in this study. RESULTS: We observed significantly increased CSF-levels of S-100b and GFAP in the hydrocephalic patients, whereas NSE and MBP were markedly increased only in patients with very severe symptoms. Serum levels of all proteins were only minimally increased and did not correlate with CSF-levels. The slightly elevated levels of CSF-NSE in most of the patients suggest only subtle neuronal damage, which is not related to permanent neurological symptoms. The elevated levels of S-100b and GFAP are indicative of a reactive astrogliosis, which has also been demonstrated in histopathological studies. No demyelination seems to occur, according to the normal levels of MBP observed in this study. CONCLUSIONS: Although CSF levels of brain specific proteins are elevated in hydrocephalic patients, indicating brain damage due to hydrocephalus, neither CSF- nor serum-concentrations of brain specific proteins seem to be valuable tools in the clinical evaluation of the severity of hydrocephalus.

A spinal intradural enterogenous cyst with well-differentiated muscularis propria.

We report a case of a newborn presenting with severe compression of the spinal cord due to a large, solitary mass extending from C4 to T2. Neurosurgical exploration revealed a large intradural, extramedullary cystic lesion, compressing the spinal cord. Slowly progressive respiratory failure due to severe myelopathy led to the death of the child 19 days postpartum. At autopsy, a well-differentiated enterogenous cyst was found, the cyst wall containing gastric and esophageal type mucosa, and a bona fide muscularis propria. The gastrointestinal tract was completely normal. The possible developmental history of intradural enterogenous cysts is discussed.

Evaluation of the traumatic coma data bank computed tomography classification for severe head injury.

This study determines the interrater and intrarater reliability of the Traumatic Coma Data Bank (TCDB) computed tomography (CT) scan classification for severe head injury. This classification grades the severity of the injury as follows: I = normal, II = diffuse injury, III = diffuse injury with swelling, IV = diffuse injury with shift, V = mass lesion surgically evacuated, or VI = mass lesion not operated. Patients with severe closed head injury were included. Outcome was assessed using the Glasgow Outcome Score (GOS) at 3 and 6 months. Four observers, two of them classifying the scans twice, independently evaluated CT scans. Of the initial CT scans of 63 patients (36 males, 27 females; age, 34+/-24 years), 6.3% were class I, 26.9% class II, 28.6% class III, 6.3% class IV, 22.2% were class V, and 9.6% class VI. The overall interrater and intrarater reliability was 0.80 and 0.85, respectively. Separate analyses resulted in higher inter- and intrarater reliabilities for the mass lesion categories (V and VI), 0.94 and 0.91, respectively, than the diffuse categories (I-IV) 0.71 and 0.67. Merging category III with IV, and V with VI resulted in inter- and intrarater reliabilities of 0.93 and 0.78, respectively. Glasgow outcome scores after 6 months were as follows: 19 dead (30%), one vegetative (2%), five severely disabled (8%), 17 moderately disabled (27%), and 21 good recovery (33%). Association measures (Sommers' D) between CT and GOS scores were statistically significant for all observers. This study shows a high intra- and interobserver agreement in the assessment of CT scan abnormalities and confirms the predictive power on outcome when the TCDB classification is used.

Subependymal giant-cell astrocytoma in tuberous sclerosis: endoscopic images and the implications for therapy.

Supratentorial intraventricular tumors are not frequently encountered in childhood. One of the most frequent intraventricular glial tumors is the subependymal giant-cell astrocytoma, mostly associated with tuberous sclerosis. These tumors are diagnosed on computed tomography (CT) or magnetic resonance imaging (MRI) scans. They can occur isolated or multiple and operative resection is advised if these tumors cause symptoms, usually raised intracranial pressure due to obstructive hydrocephalus. However, the number of tumors can be much higher than seen on radiological examination making total resection of all tumors impossible. We demonstrate this with the endoscopic images derived during the endoscopic removal of a subependymal giant-cell astrocytoma obstructing a foramen of Monro in a 15-year-old boy with tuberous sclerosis.

Meningioma of the pituitary stalk without dural attachment: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: Tumors in the suprasellar region such as adenomas of the pituitary gland, craniopharyngiomas, nonneoplastic cystic lesions (especially Rathke's cleft cysts), and meningiomas are frequently encountered in neurosurgical practice. Meningiomas originate from the arachnoid layer connected to the dura of the anterior or posterior clinoidal process, or the tuberculum, dorsum, or diaphragma sellae. Tumors originating from the pituitary stalk are rare. Such lesions may include germinomas, astrocytomas, histiocytosis X, hamartomas, and sarcoidosis. We report a patient with a suprasellar meningioma originating from the pituitary stalk with no connection to the adjacent dura. CLINICAL PRESENTATION: A 50-year-old man was assessed for impotence and loss of libido. Physical examination revealed no abnormalities. Endocrinological investigations disclosed nearly complete hypopituitarism, and magnetic resonance imaging revealed a suprasellar homogeneously enhancing tumor. INTERVENTION: Complete surgical resection was performed in an endoscope-assisted right-sided supraorbital craniotomy. The tumor originated from the pituitary stalk with no connection to the surrounding dura. The histopathological diagnosis was meningioma. CONCLUSION: Although meningiomas frequently occur in the suprasellar region, this patient with a suprasellar meningioma is unique because the tumor originated from the pituitary stalk with no connection to the surrounding dura. The absence of dural attachment has been described in 43 extracerebral meningiomas, but a suprasellar location has been reported only once previously. Recognition of this phenomenon is important, because meningiomas require a different therapeutic strategy than most other tumors of the pituitary stalk.