Idiopathic normal-pressure hydrocephalus: the cost-effectiveness of delivering timely and adequate treatment in Germany.

BACKGROUND AND PURPOSE: Idiopathic normal-pressure hydrocephalus (iNPH) is a progressive, severe brain disorder, which mainly affects people above the age of 65 years. iNPH is characterized by the accumulation of excess cerebrospinal fluid in the brain's ventricles. In most cases, iNPH patients can be effectively treated with shunt surgery, which involves placing a tube into the brain to drain the excess fluid. As part of the European Brain Council-led Value of Treatment project, this study aimed to investigate the cost-effectiveness of delivering timely and adequate iNPH treatment in Germany. METHODS: The study identified treatment gaps that prevent iNPH patients from receiving adequate and timely treatment. The cost-effectiveness of delivering shunt surgery to iNPH-prevalent patients aged ≥65 years in Germany was calculated using decision-analytical modelling. The model compared two alternatives, current care (shunt surgery in 25% of iNPH cases) and target care (shunt surgery in 90% of iNPH cases), and looked at healthcare costs (diagnosis, shunt intervention and follow-up care) from the public health insurance perspective, as well as effectiveness outcomes in terms of lives saved and quality-adjusted life-years (QALYs) gained. RESULTS: Delivering timely and adequate iNPH treatment proved to be cost-effective. Cost per life saved varied between €27 921 at 5 years and €246 726 at 15 years. Cost-per-QALY estimates varied between €10 202 at 5 years and €35 128 at 15 years. CONCLUSIONS: Idiopathic normal-pressure hydrocephalus is a treatable but often not-treated disease, resulting in unnecessary and avoidable disease burden for the healthcare system. Actions required to close this treatment gap are straightforward and their implementation has been modelled with successful outcomes.

Clinical Follow-Up of Patients with Neurocutaneous Melanosis in a Tertiary Center; Proposed Modification in Diagnostic Criteria.

INTRODUCTION: Neurocutaneous melanosis (NCM) is a rare congenital syndrome. Except for some retrospective studies, information on clinical follow-up and management of these patients are limited. This study aimed to review our experience on diagnostic protocol and clinical follow-up of patients with NCM in a referral children's hospital in Iran. METHODS: Between 2012 and 2019, eight patients with NCM were consecutively managed in our center. Brain magnetic resonance imaging and cutaneous biopsy were done in all patients at diagnosis. Follow-up surveillance and characteristics of the disease are described. RESULTS: The mean follow-up period was 25.75 ± 13.81 months, and 75% of patients were male. Most magnetic resonance imaging findings were hypersignal lesions in the temporal lobe (75%), cerebellum (62.5%), brainstem (50%), and thalamus (12.5%). Dandy-Walker syndrome was found in 4 patients (50%), and shunt-dependent hydrocephalus was found in 3 patients (37.5%). Cutaneous malignant melanoma and malignant involvement of the central nervous system were found in 2 (25%) and 3 cases (37.5%), respectively. The mortality rate was 37.5%. CONCLUSIONS: There are no specific guidelines for management of NCM due to the rarity of the disease. This study proposed modifications in diagnostic criteria, as well as recommendations for follow-up surveillance.

Surgical Indications and Operative Results of Lumbosubarachnoid-Lumboepidural Shunting in 29 Patients with Idiopathic Normal Pressure Hydrocephalus under Local Anesthesia.

This study consisted of 29 patients with idiopathic normal pressure hydrocephalus (iNPH) who underwent lumbosubarachnoid-lumboepidural (L-L) shunting under local anesthesia in accordance with our surgical indications of L-L shunting. (1) CSF absorption within the lumbar epidural space and shunt clearance were confirmed in all patients after operation. (2) Shunt responders (R) were 25 of 29 cases (86.2%) 3 months after surgery. Among the R, symptom exacerbation was confirmed in three patients (12%) within the follow-up period (mean, 25.1 months). In each of these patients, shunt function were maintained and remained unchanged even with pressure resetting, the cause being an intracranial/extracranial disease other than iNPH. (3) The initial pressure setting for this method was 8 cmH2O, with gradual change to higher pressures, such that the setting for Patient 11 and thereafter became 20 cmH2O. (4) As postsurgical complications, subcutaneous cerebral spinal fluid collection (SCC) was confirmed in five patients (17.2%). In high-pressure resetting and follow-up observation, SCC was not observed in all patients. Epidural catheter displacement was confirmed in three patients (10.3%). No recurrence was noted after the secure fixation of the catheter at the fascia insertion portion and 2 days' postsurgical bed rest. Hence, L-L shunting is an effective shunt therapy for iNPH.

Bedside placement of ventricular access devices under local anaesthesia in neonates with posthaemorrhagic hydrocephalus: preliminary experience.

PURPOSE: Posthaemorrhagic ventricular dilatation in preterm infants is primarily treated using temporising measures, of which the placement of a ventricular access device (VAD) is one option. Permanent shunt dependency rates are high, though vary widely. In order to improve the treatment burden and lower shunt dependency rates, we implemented several changes over the years. One of these changes involves the setting of the surgery from general anaesthesia in the OR to local anaesthesia in bed at the neonatal intensive care unit (NICU), which may seem counterintuitive to many. In this article, we describe our surgical technique and present the results of this regimen and compare it to our previous techniques. METHODS: Retrospective study of a consecutive series of 37 neonates with posthaemorrhagic ventricular dilatation (PHVD) treated using a VAD, with a cohort I (n = 13) treated from 2004 to 2008 under general anaesthesia in the OR, cohort II (n = 11) treated from 2009 to 2013 under general anaesthesia in the NICU and cohort III (n = 13) treated from December 2013 to December 2017 under local anaesthesia on the NICU. RESULTS: The overall infection rate was 14%; the VAD revision rate was 22% and did not differ significantly between the cohorts. Procedures under local anaesthesia never required conversion to general anaesthesia and were well tolerated. After an average of 33 tapping days, 38% of the neonates received a permanent ventriculoperitoneal (VP) shunt. The permanent VP shunt rate was 9% with VAD placement under local anaesthesia and 52% when performed under general anaesthesia (p = 0.02). CONCLUSION: Bedside placement of VADs for PHVD under local anaesthesia in neonates is a low-risk, well-tolerated procedure that results in at least equal results to surgery performed under general anaesthesia and/or performed in an OR.

Trans-nasal-trans-sphenoidal brain injury by a fencing foil: an unusual case report and brief literature review.

In this report, the authors present an unusual case of a 10-year-old child who suffered a severe headache and rhinorrhea that occurred as a result of fencing foil sports injury via trans-nasal-trans-sphenoidal (TNTS) pathway. Following trauma, the child had shown neurological symptoms such a pupil dilatation, change in consciousness and mild hemiparesia. Imaging demonstrated destruction of bone structures including posterior wall of sphenoid sinus and antero-superior part of sella turcica, and also a contusion at right thalamic region. For treatment of rhinorrhea lumbar drainage system (LDS) had planted in order to relieve cerebrospinal fluid (CSF) leakage. After the treatment, the patient had fully recovered without any need of further surgical intervention. CSF leakage had prevented and neurological symptoms were completely treated. This case represents the first report of brain injury via TNTS pathway in a sports practice. Diagnosis, clinic follow-up and treatment options of this rare accidental sports injury are discussed.

Image Guidance in Ventricular Cerebrospinal Fluid Shunt Catheter Placement: A Systematic Review and Meta-Analysis.

BACKGROUND: Ventricular shunt placement for treating hydrocephalus is one of the most common neurosurgical procedures. The rate of shunt failure, however, has not appreciably changed with time. OBJECTIVE: To investigate whether intraoperative image guidance using ultrasound or stereotaxy contributes to accurate shunt catheter placement and survival. METHODS: We performed a systematic literature review using PubMed and MEDLINE databases for studies that use ultrasound and frameless stereotaxy for ventricular catheter placement for hydrocephalus. All articles assessed the accuracy of catheter tip placement and/or overall shunt survival, and the rate of accurate shunt catheter placement, the overall failure rate, and the average time to shunt failure were extracted for analysis. RESULTS: Although each modality (ultrasound/stereotaxy) did not increase catheter placement accuracy, a combined random-effects meta-analysis of 738 catheters (136 guided by ultrasound, 168 guided by frameless stereotaxy, and 434 freehand) demonstrated a weak benefit of image guidance (risk ratio: 1.19, 95% confidence interval: 1.02-1.39, P = .02), but this result was limited by considerable heterogeneity among studies (I² = 86%, P < .001 by Cochrane's Q test). A meta-analysis could not be performed for shunt survival due to heterogeneity in data reporting. CONCLUSION: Although image guidance offers a promising solution to lower the risk of inaccurate catheter placement, which could lead to lower premature failure of ventricular shunts, our review demonstrated that there is not yet a clear benefit of these technologies. Current literature is limited to case series and cohort studies, and significant between-study heterogeneity in methodology and reporting currently limits a higher order analysis.

[Shunt passer clamp: a new device to prevent rotation of CSF-shunt passer].

Cerebrospinal fluid shunting is a surgical treatment alternative for hydrocephalus. In general, ventriculoperitoneal (VP) and lumboperitoneal (LP) shunts have been widely practiced as standard procedures. However, these procedures are difficult because the shunt passer often rotates unintentionally. Therefore, we developed a simple device that prevents shunt passer rotation and termed it a "shunt passer-clamp"(SP-C). This device consists of two parts: the first part is the body with a hole through which the passer goes and a "female" screw perpendicular to the hole. The second part is a "male" screw set to the body. The surgeon can attach the SP-C to the shunt passer without the requirement for remodeling. We employed a SP-C for 14 consecutive shunt surgeries and received favorable feedback from the surgeons. Handling was considered "easy" in all cases. The surgical duration was significantly shorter than that if the SP-C was not employed. We conclude that our specially designed SP-C is relatively effective.

The neurosurgical treatment of Alzheimer's disease: a review.

BACKGROUND: Alzheimer's disease (AD) is a debilitating neurological illness of increasing prevalence. Because many patients are affected and current treatments have limited effectiveness, other therapeutic strategies are urgently needed. OBJECTIVES: Here we provide a review of the neurosurgical approaches that have been attempted or are currently being investigated for the treatment of AD. METHODS: Computerized database searches identified all of the published studies in the English-language literature examining the surgical treatment of AD since 1950. RESULTS: The following 5 categories of neurosurgical treatment were identified: cerebrospinal fluid shunting, intraventricular infusions, tissue grafting, gene therapy, and electrical neural stimulation. CONCLUSIONS: While none of the neurosurgical approaches applied to the treatment of AD have proven effective to date, recent trials involving gene therapy and electrical neural stimulation are showing promising early results. Larger trials investigating these treatments have been proposed or are currently under way.

Sylvian cistern arachnoid cyst--a rare cause of precocious puberty.

Precocious puberty still remains an elusive diagnosis in the majority of patients. Infrequently, lesions of the central nervous system are associated with sexual precocity. Depending on their location, these cysts may affect many systems, however, there is little information concerning their involvement in endocrinological disorders. We report a case of a sylvian cistern arachnoid cyst presenting with precocious puberty in a 3-year-old girl. The child recovered following a cystoperitoneal shunt. The mass effect of the arachnoid cyst upon the hypothalamus was, at least in part, responsible for the development of precocious puberty. To the best of our knowledge, this is the 1st case of a sylvian cistern arachnoid cyst presenting with precocious puberty. The role of surgical decompression of the cyst is also discussed.

Posthemispherectomy hydrocephalus: results of a comprehensive, multiinstitutional review.

PURPOSE: Hemispherectomy surgery for medically intractable epilepsy is known to cause hydrocephalus in a subset of patients. Existing data regarding the incidence of, and risk factors for, developing posthemispherectomy hydrocephalus have been limited by the relatively small number of cases performed by any single center. Our goal was to better understand this phenomenon and to identify risk factors that may predispose patients to developing hydrocephalus after hemispherectomy surgery. METHODS: Fifteen pediatric epilepsy centers participated in this study. A retrospective chart review was performed on all available patients who had hemispherectomy surgery. Data collected included surgical techniques, etiology of seizures, prior brain surgery, symptoms and signs of hydrocephalus, timing of shunt placement, and basic demographics. KEY FINDINGS: Data were collected from 736 patients who underwent hemispherectomy surgery between 1986 and 2011. Forty-six patients had preexisting shunted hydrocephalus and were excluded from analysis, yielding 690 patients for this study. One hundred sixty-two patients (23%) required hydrocephalus treatment. The timing of hydrocephalus ranged from the immediate postoperative period to 8.5 years after surgery, with 43 patients (27%) receiving shunts >90 days after surgery. Multivariate regression analysis revealed anatomic hemispherectomies (odds ratio [OR] 4.1, p < 0.0001) and previous brain surgery (OR 1.7, p = 0.04) as independent significant risk factors for developing hydrocephalus. There was a trend toward significance for the use of hemostatic agents (OR 2.2, p = 0.07) and the involvement of basal ganglia or thalamus in the resection (OR 2.2, p = 0.08) as risk factors. SIGNIFICANCE: Hydrocephalus is a common sequela of hemispherectomy surgery. Surgical technique and prior brain surgery influence the occurrence of posthemispherectomy hydrocephalus. A significant portion of patients develop hydrocephalus on a delayed basis, indicating the need for long-term surveillance.

Evaluation of an institutional guideline for the treatment of cerebrospinal fluid shunt-associated infections.

BACKGROUND: Cerebrospinal fluid (CSF) shunt-associated infection is one of the most frequent complications of CSF shunt surgery. We evaluated our institutional guideline for the treatment of shunt-associated infections. METHODS: We retrospectively analysed all 92 episodes of shunt-associated infections in 78 patients treated in our institution from 2002 to 2008. All patients underwent urgent surgery, i.e. removal of the complete shunt hardware or externalisation of the distal tubing in cases with an infection restricted to the distal shunt (10 %), placement of an external ventricular drainage as necessary and antibiotic therapy. Standard empirical first-line antibiotic treatment consisted of a combination of flucloxacillin and cefuroxime. RESULTS: We observed 38 % early (<1 month after shunt surgery) and 20 % late infections (> 1 year after shunt placement). Coagulase-negative staphylococci (CoNS) were isolated in 38 %. In 38 % no pathogens could be isolated. Of cases with a first shunt infection, 58 % were initially treated with flucloxacillin/cefuroxime. Only 53 % of all infections were treated successfully with the first course of antibiotics. Only 51 % of bacterial isolates were sensitive to empirical first-line antibiotics. Twenty percent of infections caused by sensitive bacterial isolates nevertheless required second-line antibiotic therapy. CONCLUSIONS: Urgent surgery for shunt removal and antibiotic therapy will usually cure a shunt-associated infection. The choice of antibiotics should reflect the spectrum of pathogens seen at one's institution, paying particular attention to the role of CoNS isolates, and in vitro sensitivity testing results.

[Cervical meningocele with filiform connection. Case report]. / Meningocele cervical con conexión filiforme. Reporte de un caso.

The meningocele is the least common form of spina bifida cystica and represents less than 10% of cases of this disorder. A case of a female patient aged 26 with a history of two pregnancies and two previous cesarean sections, present pregnancy unplanned, uncontrolled during the first trimester prenatal and without supplementation with folic acid. Family history of consanguinity with her husband (second cousins) and psychomotor reassessed in four maternal cousins. The first follow-up visit the patient was at 34 weeks of pregnancy. The ultrasonographic findings were: cervical meningocele posterior filiform connection between the first and second cervical vertebrae, lateral ventriculomegaly and third and fourth ventricles and hydrocephalus secondary. Cesarean section was performed at 37 weeks gestation and was a newborn male 3.000 g, 52 cm, head circumference of 36 cm, Apgar 8/9, Capurro 37 weeks of gestation. In the posterior cervical region tumor was located a soft 5 x 5 cm with intact skin, adhered to deep planes. Movement of all four extremities without neurological involvement. He referred to the department of neurosurgery for shunt placement and subsequently performed surgical excision of the meningocele.

Cystoperitoneal shunt for a giant intrathoracic meningocele under local anesthesia.

Giant intrathoracic meningoceles are extremely rare, and the standard treatment for giant intrathoracic meningoceles remains controversial. We present the case of a patient with giant intrathoracic meningoceles associated with neurofibromatosis type I. Our patient had poor respiratory function because of the giant intrathoracic meningocele, so we performed a cystoperitoneal shunt under local anesthesia. We describe our cystoperitoneal shunt technique using an adjustable-pressure valve. This simple, minimally invasive treatment is a valuable alternative treatment option in patients at high operative risk, especially those with low respiratory function.

Ventriculovascular shunts via the femoral vein: a temporary feasible alternative in pediatric hydrocephalus.

Ventriculovascular shunts via the femoral vein have been described as a feasible alternative for cerebrospinal fluid diversion in those complex cases of hydrocephalus in which other accesses are discarded. However, experience is short. To our knowledge, only 4 cases have been reported in the literature to date. We report 2 cases of hydrocephalic children who were developed several complications related to ventriculoperitoneal and ventriculoatrial shunts and who successfully managed by means of ventriculovascular shunts via the femoral vein. Both patients underwent vascular catheter placement through a venotomy performed in the common femoral vein. Catheter advance was controlled under fluoroscopic guidance. Distal catheters were joined by means of a straight connector, and a loop was accommodated in a subcutaneous pocket in the inguinal region to avoid future complications. The femoral vein is a successful alternative approach for distal catheter placement in ventriculovascular shunts when other accesses are ruled out.

[Effect of magnetic fields from home-use magnetic induction therapy apparatuses on adjustable cerebrospinal fluid shunt valves].

OBJECTIVE: Cerebrospinal fluid (CSF) shunts are frequently used to treat hydrocephalus. The use of a programmable valve allows the operator to easily change the opening pressure. In Japan, many people use magnetic induction therapy apparatuses in their homes. However, exposing patients with adjustable CSF shunt valves to the permanent magnets included in these apparatuses may alter the shunt valve's programmed settings or permanently damage the device. Therefore, the goal of this study was to determine the health risk associated with magnetic induction therapy for patients using programmable CSF shunt valves. METHODS: Five models of shunt valves from five different manufacturers, the Miethke proGAV (proGAV), the Codman Hakim programmable valve (CHPV), Sophysa Sophy model SM8 (Sophy valve), Sophysa Polaris model SPV (Polaris valve), and Strata II valve (Strata valve) were evaluated in this study. Magnetic field interactions were determined for the programmable valves by using magnetic stones with various magnetic flux densities. The maximum distance between the valve and the magnetic stone affecting the valve pressure setting was measured by X-ray. RESULTS: The proGAV and Polaris valve were immune to unintentional reprogramming by the magnetic stones. The CHPV, Sophy valve and Strata valve, however, randomly changed settings by magnetic stones. CONCLUSIONS: Whereas the CHPV, Sophy valve and Strata valve were promptly reset by exposure to a magnetic stone with a similar strength to that used in magnetic induction therapy, proGAV and Polaris valve were resistant to inadvertent reprogramming when exposed to magnets up to 190 mT.

The impact of microsurgical fenestration of the lamina terminalis on shunt-dependent hydrocephalus and vasospasm after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Chronic hydrocephalus requiring shunt placement and cerebral vasospasm are common complications after aneurysmal subarachnoid hemorrhage. Recent publications have investigated the possibility that microsurgical fenestration of the lamina terminalis during aneurysm surgery may reduce the incidence of shunt-dependent hydrocephalus and cerebral vasospasm. We reviewed a single-surgeon series to compare postsurgical outcomes of patients who underwent fenestration of the lamina terminalis against those who did not. METHODS: This study is a retrospective review of the medical records of 369 consecutive patients with aneurysmal subarachnoid hemorrhage admitted to Columbia University Medical Center between January 2000 and July 2006. All patients underwent craniotomy and clipping of at least one ruptured cerebral aneurysm by a single neurosurgeon (ESC). The incidences of shunt-dependent hydrocephalus, conversion from acute hydrocephalus on admission to chronic hydrocephalus, and clinical cerebral vasospasm were compared in patients who underwent fenestration of the lamina terminalis with those who did not. The patient cohort was thus divided into three subgroups: 1) patients whose operative records clearly indicated that they underwent fenestration of the lamina terminalis, 2) patients whose operative records clearly indicated that they did not undergo fenestration of the lamina terminalis, and 3) patients whose operative records did not indicate one way or another whether they received fenestration of the lamina terminalis. We performed two separate analyses by comparing the postsurgical outcomes in those patients who were fenestrated versus those who were definitively not fenestrated and comparing the postsurgical outcomes in those patients who were fenestrated versus those who were not plus those whose records did not document fenestration. To further control for any cohort differences, we performed a comparison between patients who were fenestrated and those who were not after matching 1:1 for presenting radiographic and clinical characteristics predictive of hydrocephalus and vasospasm. Outcomes were compared using logistic regression and multivariable analysis. RESULTS: In the first model, fenestrated patients had a shunt rate, conversion rate, and rate of clinical vasospasm of 25, 50, and 23%, respectively, versus 20, 27, and 27% in nonfenestrated patients, respectively (P = 0.28, 0.21, and 0.32, respectively). In the second model, the nonfenestrated patients plus nondocumented patients had a shunt rate, conversion rate, and rate of clinical vasospasm of 16, 40, and 20%, respectively (P = 0.19, 0.33, and 0.60, respectively). In the matched cohort, fenestrated patients had a shunt rate, conversion rate, and rate of clinical vasospasm of 29, 67, and 20%, respectively, versus 20, 25, and 25% in nonfenestrated patients, respectively (P = 0.30, 0.24, and 0.20, respectively). CONCLUSION: In contrast to other retrospective multisurgeon series, our retrospective single-surgeon series suggests that microsurgical fenestration of the lamina terminalis may not reduce the incidence of shunt-dependent hydrocephalus or cerebral vasospasm after aneurysmal subarachnoid hemorrhage. A prospective multicenter trial is needed to definitively address the use of this maneuver.

Design of an intelligent and personalised shunting system for hydrocephalus.

Hydrocephalus is a neurological disease that manifests itself in an elevated fluid pressure within the brain, and if left untreated, may be fatal. It is currently treated using shunt implants, which consist of a mechanical valve and tubes that regulate the pressure of cerebrospinal fluid (CSF) by draining excess fluid into the abdomen. Hydrocephalus shunting systems are no longer expected simply to regulate the intracranial pressure (ICP), but also to offer the option of regaining independence of the shunt. Additionally, they could offer personalised valve management which is one of the main limitations of current shunts. This paper describes the design of a multi-agent system for an intelligent and personalised CSF management system. Patient feedback and intracranial pressure readings will play important roles in the process of CSF regulation and weaning, introduces an element of personalisation to the treatment. The new shunting system would deliver both reactive and goal-driven solutions for the treatment, at the same time the intelligent part of the system will be monitoring how well the shunt is performing. These tasks can be achieved by implementing an agent approach in designing this system. Such system would help us to understand more about the dynamics of hydrocephalus.

Thalamic tumors in children: a reappraisal.

OBJECT: Two to five percent of pediatric brain tumors are located in the thalamus. The optimal management for these tumors remains unclear. The aim of this study was to determine whether clinical and neuroimaging features could guide treatment, and to what extent these features, together with histological diagnosis and treatment modalities, influenced survival. METHODS: The records of 69 children who presented with a thalamic tumor between 1989 and 2003 were retrospectively reviewed. Three groups of tumors were analyzed separately: 1) unilateral thalamic tumors (54 lesions); 2) thalamopeduncular tumors (six); and 3) bilateral thalamic tumors (nine). In the patients in whom a unilateral thalamic tumor was diagnosed, 33 had an astrocytic tumor. Of the 54 patients, 32 had a low-grade and 22 had a high-grade tumor. The survival rate was significantly better for patients with the following characteristics: symptom duration longer than 2 months (p < 0.001), lesions with low-grade histological features (p = 0.003), and tumor excision greater than 90% at surgery (p = 0.04). The perioperative morbidity and mortality rates were 37 and 4%, respectively. Fifty-four percent of the patients in this group had a long-term and independent survival. The thalamopeduncular tumors were mostly pilocytic astrocytomas, which had a good prognosis following surgery. The bilateral thalamic tumors in this series were mainly low-grade astrocytic lesions, and more than half of the children attained long-term survival (mean follow-up duration 4.5 years). CONCLUSIONS: The majority of tumors arising in the thalamus are astrocytic, of which less than half are high-grade lesions. Histological evaluations should be performed in all patients in whom resection is being considered for discrete lesions. Long-term survival is possible in patients with these tumors.

Antibiotic prophylaxis in cerebrospinal fluid shunting: reassessment of Cefotiam penetration into human CSF.

OBJECTS: Shunt infection is a major complication of shunt implantation. Numerous clinical studies give evidence that antibiotic prophylaxis is efficacious in preventing infections after cerebrospinal fluid shunting. In CSF shunting, antibiotics need to reach sufficient concentrations not only in the blood shielding the operative field but also in tissues and the CSF compartment. Cefotiam is widely used for prophylaxis in neurosurgery. Some clinical trials report that this beta-lactam is able to penetrate considerably into the CSF. However, these studies include disease patterns which are most likely to be associated with a pathological permeability of the blood-brain barrier. Therefore, this study was designed to investigate the extent of penetration of Cefotiam into human CSF in patients without morphological disruption of the blood-brain barrier. METHODS: The penetration of Cefotiam into human CSF was investigated in 23 patients without morphological disruption of the blood-brain barrier undergoing CSF shunt surgery. 2 g Cefotiam was administered prior to surgery as a short-term infusion for a period of 15 min. Samples of blood and CSF were collected intraoperatively. The concentrations of Cefotiam were determined by bioassay. RESULTS: All patients (n=23) showed moderate to high plasma levels of Cefotiam (range: 19.8-146.2 mg/L); the pharmacokinetic profiles in blood accorded well with published data. In contrast to earlier studies, no Cefotiam was detected in CSF. CONCLUSION: This study clearly demonstrates that Cefotiam does not penetrate through an intact blood-brain barrier into human CSF. Although Cefotiam has been shown to be valuable for the perioperative prophylaxis of shunt infection, other antibiotics might be superior if they are capable of entering the CSF. Further studies are required to address this assumption.