Linezolid in Neurosurgery

Linezolid in Neurosurgery

Relevant studies were identified through searches of the PubMed, Current Contents, and Cochrane databases (publications archived until October 2006).

Case reports, case series, prospective and retrospective studies, and randomized controlled trials were eligible for inclusion in our review if they evaluated the effectiveness and safety of linezolid for the treatment of patients with CNS infections.

In 18 (42.9%) of the 42 relevant cases identified, patients had undergone neurosurgical operations and/or had prosthetic devices. Meningitis was the most common CNS infection, accounting for 20 (47.6%) cases. Other CNS infections included brain abscesses (14; 33.3%), ventriculitis (5; 11.9%), and ventriculo-peritoneal shunt infection (3; 7.1%). In the 39 patients in whom the responsible pathogen was isolated, those predominantly responsible for the CNS infections were: penicillin-nonsusceptible Streptococcus pneumoniae (7; 17.9%), vancomycin-resistant enterococci (6; 15.4%), Nocardia spp. (5; 12.8%), methicillin-resistant Staphylococcus epidermidis (4; 10.3%), and methicillin-resistant Staphylococcus aureus (3; 7.7%). Of the 42 patients who received linezolid for the treatment of CNS infections, 38 (90.5%) were either cured or showed clinical improvement of the infection. The mean duration of follow-up was 7.2 months; no recurrent CNS infection was reported.

The limited published data suggest that linezolid may be considered for the treatment of patients with CNS infections in cases of failure of previously administered treatment or limited available options 2).

To evaluate the efficacy and safety of SAT with oral linezolid in patients with NSI and to analyse the cost implications, an observational, non-comparative, prospective cohort study was conducted on clinically stable consecutive adult patients at the Neurosurgical Service. Following intravenous treatment, patients were discharged with SAT with oral linezolid.

A total of 77 patients were included. The most common NSIs were: 41 surgical wound infections, 20 subdural empyemas, 18 epidural abscesses, and 16 brain abscesses. Forty-four percent of patients presented two or more concomitant NSIs. Aetiological agents commonly isolated were: Propionibacterium acnes (36 %), Staphylococcus aureus (23 %), Staphylococcus epidermidis (21 %) and Streptococcus spp. (13 %). The median duration of the SAT was 15 days (range, 3-42). The SAT was interrupted in five cases due to adverse events. The remainder of the patients were cured at the end of the SAT. A total of 1,163 days of hospitalisation were saved. An overall cost reduction of €516,188 was attributed to the SAT. Eight patients with device infections did not require removal of the device, with an additional cost reduction of €190,595. The mean cost saving per patient was €9,179.

SAT with linezolid was safe and effective for the treatment of NSI. SAT reduces hospitalisation times, which means significant savings of health and economic resources 3).


Seventeen patients were included in the study. The main comorbidities among these patients included one or more of the following: subarachnoidal or intraventricular hemorrhage (n=8), solid neurological cancer (n=7), corticosteroids(n=9), and hydrocephalus (n=6). Eight patients underwent a craniotomy and fourteen patients had external ventricular drainage (EVD) as a predisposing factor for infection. Meningitis was the most common infection (11; 64.7%), followed by ventriculitis (4; 23.5%) and brain abscesses (2;11.8%). The main causative organisms were coagulase-negative Staphylococcus spp. (13; 76.5%). Linezolid was used as the initial therapy in 8 episodes, after therapy failure in 6, and for other reasons in 3. The oral route was used in 9 (52.9%) episodes; linezolid was initiated orally in 2 cases. The mean duration of treatment was 26.5 days (range 15-58). No adverse events were reported. Sixteen (94.1%) patients were considered cured. There was one recurrence. The mean length of hospital stay was 45.6 (range 15-112) days and the mean duration of follow-up was 7.2 (range 0.4-32) months. No related deaths occurred during active episodes.

Linezolid was mainly indicated in post-neurosurgical EVD-associated infections due to coagulase-negative Staphylococcus spp. It was used as initial therapy in most cases. A high rate of clinical cure was observed and no related adverse events were reported. More than half of the patients benefited from the advantages of the oral route of administration 4).


In order to study the penetration of this antimicrobial into the cerebrospinal fluid (CSF) of such patients, the disposition of linezolid in serum and CSF was studied in 14 neurosurgical patients given linezolid at 600 mg twice daily (1-h intravenous infusion) for the treatment of CNS infections caused by gram-positive pathogens or for prophylactic chemotherapy. Serum and CSF linezolid steady-state concentrations were analyzed by high-pressure liquid chromatography, and the concentration-time profiles obtained were analyzed to estimate pharmacokinetic parameters. The mean +/- standard deviation (SD) linezolid maximum and minimum measured concentrations were 18.6 +/- 9.6 microg/ml and 5.6 +/- 5.0 microg/ml, respectively, in serum and 10.8 +/- 5.7 microg/ml and 6.1 +/- 4.2 microg/ml, respectively, in CSF. The mean +/- SD areas under the concentration-time curves (AUCs) were 128.7 +/- 83.9 microg x h/ml for serum and 101.6 +/- 59.6 microg x h/ml for CSF, with a mean penetration ratio for the AUC for CSF to the AUC for serum of 0.66. The mean elimination half-life of linezolid in CSF was longer than that in serum (19.1 +/- 19.0 h and 6.5 +/- 3.6 h, respectively). The serum and CSF linezolid concentrations exceeded the pharmacodynamic breakpoint of 4 microg/ml for susceptible target pathogens for the entire dosing interval in the majority of patients. These findings suggest that linezolid may achieve adequate concentrations in the CSF of patients requiring antibiotics for the management or prophylaxis of CNS infections caused by gram-positive pathogens 5).


1)

Jahoda D, Nyc O, Pokorný D, Landor I, Sosna A. [Linezolid in the treatment of antibiotic-resistant gram-positive infections of the musculoskeletal system]. Acta Chir Orthop Traumatol Cech. 2006 Oct;73(5):329-33. Czech. PubMed PMID: 17140514.
2)

Ntziora F, Falagas ME. Linezolid for the treatment of patients with central nervous system infection. Ann Pharmacother. 2007 Feb;41(2):296-308. Epub 2007 Feb 6. Review. PubMed PMID: 17284501.
3)

Martín-Gandul C, Mayorga-Buiza MJ, Castillo-Ojeda E, Gómez-Gómez MJ, Rivero-Garvía M, Gil-Navarro MV, Márquez-Rivas FJ, Jiménez-Mejías ME. Sequential antimicrobial treatment with linezolid for neurosurgical infections: efficacy, safety and cost study. Acta Neurochir (Wien). 2016 Oct;158(10):1837-43. doi: 10.1007/s00701-016-2915-0. Epub 2016 Aug 13. PubMed PMID: 27520361.
4)

Sousa D, Llinares P, Meijide H, Gutiérrez JM, Miguez E, Sánchez E, Castelo L, Mena A. Clinical experience with linezolid for the treatment of neurosurgical infections. Rev Esp Quimioter. 2011 Mar;24(1):42-7. PMID: 21412669.
5)

Myrianthefs P, Markantonis SL, Vlachos K, Anagnostaki M, Boutzouka E, Panidis D, Baltopoulos G. Serum and cerebrospinal fluid concentrations of linezolid in neurosurgical patients. Antimicrob Agents Chemother. 2006 Dec;50(12):3971-6. doi: 10.1128/AAC.00051-06. Epub 2006 Sep 18. PMID: 16982782; PMCID: PMC1694012.

American Society for Stereotactic and Functional Neurosurgery

American Society for Stereotactic and Functional Neurosurgery

https://www.assfn.org/

Magnetic resonance image-guided laser interstitial thermal therapy (MRgLITT) is a tool in the neurosurgical armamentarium for the management of drug-resistant epilepsy. Given the introduction of this technology, the American Society for Stereotactic and Functional Neurosurgery (ASSFN), which acts as the joint section representing the field of stereotactic and functional neurosurgery on behalf of the Congress of Neurological Surgeons and the American Association of Neurological Surgeons, provides here the expert consensus opinion on evidence-based best practices for the use and implementation of this treatment modality. Indications for treatment are outlined, consisting of failure to respond to, or intolerance of, at least 2 appropriately chosen medications at appropriate doses for disabling, localization-related epilepsy in the setting of well-defined epileptogenic foci, or critical pathways of seizure propagation accessible by MRgLITT. Applications of MRgLITT in mesial temporal lobe epilepsy and hypothalamic hamartoma, along with its contraindications in the treatment of epilepsy, are discussed based on current evidence. To put this position statement in perspective, they detailed the evidence and authority on which this ASSFN position statement is based 1)

A persistent underuse of epilepsy surgery exists. Neuromodulation treatments including deep brain stimulation (DBS) expand the surgical options for patients with epilepsy and provide options for patients who are not candidates for resective surgery. DBS of the bilateral anterior nucleus of the thalamus is an Food and Drug Administration-approved, safe, and efficacious treatment option for patients with refractory focal epilepsy. The purpose of this consensus position statement is to summarize evidence, provide recommendations, and identify indications and populations for future investigation in Deep Brain Stimulation for epilepsy. The recommendations of the American Society for Stereotactic and Functional Neurosurgery are based on several randomized and blinded clinical trials with high-quality data to support the use of DBS to the anterior nucleus of the thalamus for the treatment of refractory focal-onset seizures.

Cabrera et al. designed a 51-question online survey comprising Likert-type, multiple-choice, and rank-order questions and distributed it to members of the American Society for Stereotactic and Functional Neurosurgery (ASSFN). Descriptive and inferential statistical analyses were performed on the data.

They received 38 completed surveys. Half (n = 19) of responders reported devoting at least a portion of their clinical practice to psychiatric neurosurgery, utilizing DBS and treating obsessive compulsive disorder (OCD) most frequently overall. Respondents indicated that psychiatric neurosurgery is more medically effective (OR 0, p = 0.03242, two-sided Fisher’s exact test) and has clearer clinical indications for the treatment of OCD than for the treatment of depression (OR 0.09775, p = 0.005137, two-sided Fisher’s exact test). Seventy-one percent of all respondents (n = 27) supported the clinical utility of ablative surgery in modern neuropsychiatric practice, 87% (n = 33) agreed that ablative procedures constitute a valid treatment alternative to DBS for some patients, and 61% (n = 23) agreed that ablative surgery may be an acceptable treatment option for patients who are unlikely to comply with postoperative care.

This up-to-date account of practices, perceptions, and predictions about psychiatric neurosurgery contributes to the knowledge about evolving attitudes over time and informs priorities for education and further surgical innovation on the psychiatric neurosurgery landscape 2).

2022 AMERICAN SOCIETY FOR STEREOTACTIC AND FUNCTIONAL NEUROSURGERY BIENNIAL MEETING

2016 Biennial Meeting of the American Society for Stereotactic and Functional Neurosurgery, Chicago, IL, USA, June 18-21, 2016: Abstracts 3)


1)

Wu C, Schwalb JM, Rosenow JM, McKhann GM 2nd, Neimat JS; American Society for Stereotactic and Functional Neurosurgeons. The American Society for Stereotactic and Functional Neurosurgery Position Statement on Laser Interstitial Thermal Therapy for the Treatment of Drug-Resistant Epilepsy. Neurosurgery. 2022 Feb 1;90(2):155-160. doi: 10.1227/NEU.0000000000001799. PMID: 34995216.
2)

Cabrera LY, Courchesne C, Kiss ZHT, Illes J. Clinical Perspectives on Psychiatric Neurosurgery. Stereotact Funct Neurosurg. 2019;97(5-6):391-398. doi: 10.1159/000505080. Epub 2020 Jan 17. PMID: 31955163.
3)

2016 Biennial Meeting of the American Society for Stereotactic and Functional Neurosurgery, Chicago, IL, USA, June 18-21, 2016: Abstracts. Stereotact Funct Neurosurg. 2017 Jan 16;94 Suppl 2:1-77. doi: 10.1159/000455386. [Epub ahead of print] PubMed PMID: 28092908.

Resective epilepsy surgery

Resective epilepsy surgery

Resective epilepsy surgery based on an invasive EEG-monitors performed with subdural grids (SDG) or depth electrodes (stereoelectroencephalographySEEG) is considered to be the best option towards achieving seizure-free state in drug resistant epilepsy.

Despite good outcomes from high-quality clinical trials, referrals of patients with seizures refractory to medical treatment remain infrequent 1).

Three RCTs (two adult RCTs and one pediatric RCT) consistently supported the efficacy of resective surgery as treatment for epilepsy with semiology localized to the mesial temporal lobe. In these studies, 58-100% of the patients who underwent resective surgery achieved seizure freedom, in comparison to 0-13% of medically treated patients. In another RCT, the likelihood of seizure freedom after resective surgery was independent of the surgical approach (transSylvian [64%] versus subtemporal [62%]). Two other RCTs demonstrated that hippocampal resection is essential to optimize seizure control. But, no significant gain in seizure control was achieved beyond removing 2.5 cm of the hippocampus. Across RCTs, minor complications (deficit lasting < 3 months) and major complications (deficit > 3 months) ranged 2-5% and 5-11% respectively. However, nonincapacitating superior subquadrantic visual-field defects (not typically considered a minor or major complication) were noted in up to 55% of the surgical cohort. The available RCTs provide compelling support for resective surgery as a treatment for mesial temporal lobe epilepsy and offer insights toward optimal surgical strategy 2)

Complete removal of the epileptogenic zone significantly increases the chances for postoperative seizure-freedom. In complex surgical candidates, delineation of the epileptogenic zone requires a long-term invasive video/EEG from intracranial electrodes. It is especially challenging to achieve a complete resection in deep brain structures such as opercular insular cortex 3).

Belohlavkova et al. retrospectively reviewed data of pediatric patients operated in Motol Epilepsy Center between October 2010 and June 2020 who underwent resections guided by intraoperative visual detection of depth electrodes following SEEG. The outcome in terms of seizure- and AED-freedom was assessed individually in each patient.

Nineteen patients (age at surgery 2.9-18.6 years, median 13 years) were included in the study. The epileptogenic zone involved opercular insular cortex in eighteen patients. The intraoperative detection of the electrodes was successful in seventeen patients and the surgery was regarded complete in sixteen. Thirteen patients were seizure-free at final follow-up including six drug-free cases. The successful intraoperative detection of the electrodes was associated with favorable outcome in terms of achieving complete resection and seizure-freedom in most cases. On the contrary, the patients in whom the procedure failed had poor postsurgical outcome.

The reported technique helps to achieve the complete resection in challenging patients with the epileptogenic zone in deep brain structures 4)


81 patients with tuberous sclerosis complex (TSC) who had undergone resective epilepsy surgery at Sanbo Brain Hospital, between April 2004 and June 2019. They estimated the cumulative probability of remaining seizure-free and plotted survival curves. Variables were compared using Mann-Whitney U, Pearson’s correlation, continuity correction, and Fisher’s exact chi-square tests. Prognostic predictors were analyzed using log-rank (Mantel-Cox) tests and Cox regression models.

At the last follow-up, 48 (59.3%) patients were classified as International League Against Epilepsy Class 1 (including 14 patients who had seizures <3 times postoperatively on the same or different day and were seizure-free at all other times). The estimated cumulative probability of remaining seizure-free postoperatively was 69.0% (95% confidence interval [CI] 58.8-79.2%), 61.9% (95% CI 51.1-72.7%), and 55.0% (95% CI 42.8-67.2%) at 2, 5, and 10 years, respectively. The mean time of remaining seizure-free was 7.24 ± 0.634 years (95% CI 6.00-8.49); en bloc resection was an essential positive predictor of postoperative seizure freedom, as was age at seizure onset, regional interictal video-electroencephalography pattern, and temporal lobe surgery. The longer the seizure-free time, the less likely a relapse. Patients who postoperatively experienced seizures remained likely to recover.

They demonstrated the efficacy of tuberous sclerosis complex treatment and intractable epilepsy with surgery. Detailed perioperative tests are a reliable predictor of postoperative seizure freedom 5)


1)

Jobst BC, Cascino GD. Resective epilepsy surgery for drug-resistant focal epilepsy: a review. JAMA. 2015 Jan 20;313(3):285-93. doi: 10.1001/jama.2014.17426. PMID: 25602999.
2)

Cramer SW, McGovern RA, Wang SG, Chen CC, Park MC. Resective epilepsy surgery: assessment of randomized controlled trials. Neurosurg Rev. 2021 Aug;44(4):2059-2067. doi: 10.1007/s10143-020-01432-x. Epub 2020 Nov 9. PMID: 33169227.
3) , 4)

Belohlavkova A, Jahodova A, Kudr M, Benova B, Ebel M, Liby P, Taborsky J, Jezdik P, Janca R, Kyncl M, Tichy M, Krsek P. May intraoperative detection of stereotactically inserted intracerebral electrodes increase precision of resective epilepsy surgery? Eur J Paediatr Neurol. 2021 Sep 25;35:49-55. doi: 10.1016/j.ejpn.2021.09.012. Epub ahead of print. PMID: 34610561.
5)

Huang Q, Zhou J, Wang X, Li T, Wang M, Wang J, Teng P, Qi X, Zhu M, Luan G, Zhai F. Predictors and Long-term Outcome of Resective Epilepsy Surgery in Patients with Tuberous Sclerosis Complex: A Single-centre Retrospective Cohort Study. Seizure. 2021 Mar 25;88:45-52. doi: 10.1016/j.seizure.2021.03.022. Epub ahead of print. PMID:

Brainstem Neurosurgery

Brainstem Neurosurgery

by Michael Ghali (Author), George Ghali (Author)

List Price: $199.33

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Microsurgical operations in the vicinity of the bulb or its intraaxial contents is frequently fraught with operator angst and catastrophic neurologic deficits. Accordingly, the most rudimentary of Nature’s beautiful creations also happens to be among its most complex and delicate. The brainstem houses the core circuitry generating sympathetic tone and a breathing rhythm which maintain Life. The reticular activating propriobulbar circuitry diffusely projects and activates cerebral cortex directly and through thalamic relay nuclei to maintain Vigilance. Cranial nerve motor nuclei control the movements of the head and neck and cranial sensory nuclei represent the initial relays transmitting somatosensory information of the face and cephaloviscera to the ventral posterior medial thalamic nuclei. These nuclei are complexly, though discretely and wisely organized within its interior and multimodally modulated by suprabulbar and peripheral influences. Haphazard microsurgical maneuvers or the slightest transgression upon one of its critical structures may hasten and expedite a patient’s rapid demise. Fortuitously, innovation in microsurgical techniques by the works of Emeritus Professor Dr. Robert F. Spetzler and Emeritus Professor Dr. Albert I. Rhoton has provided us with an elegant set of operative steps to achieve the safe and effective removal of pathology sans deficit, rendering the safe removal of previously inoperable neoplastic and vascular lesions commonplace and facile. Familiarity, versatility, and comfort with the faithful performance of these techniques augment the neurosurgeon’s armamentarium and confidence to intervene upon brainstem proximate and intraaxial pathology.

Neurosurgery Exit Exam Preparation/ Basic Anatomy of Ventricles

Neurosurgery Exit Exam Preparation/ Basic Anatomy of Ventricles


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The World of Neurosurgery: New Articles Out Now

The World of Neurosurgery: New Articles Out Now

Neurosurgeons around the world are united by their desire to help patients, especially in these unpredictable times. In the latest articles from AANS Neurosurgeon, authors share experiences of global neurosurgery and how the field has developed over time. New today:

Roger Stupp, MD; Mark Youngblood, MD, PhD

Martina Stippler, MD, FAANS; Jaini Shah

H. Hunt Batjer, MD, FAANS

Clarence B. Watridge, MD, FAANS(L)

Gail Rosseau, MD, FAANS; Walter D. Johnson, MD, FAANS(L)

Scott C. Mitchell

Gary D. VanderArk, MD, FAANS

The Search for a Biological Link between Reactivated HSV and Neurological Disease

Without even knowing it, most of us carry around latent Herpes Simplex Virus (HSV) in our nervous system—a simple result of being born and living together with others carrying the virus.

Aerobic Exercise May Treat Persistent Post-concussive Symptoms in Adults

A new study will evaluate whether persistent symptoms following concussion, also known as post-concussion syndrome, can be treated using a personalized, progressive aerobic exercise program.

Novel use of Robotics for Neuroendovascular Procedures

Surgeons at the Sidney Kimmel Medical College at Thomas Jefferson University are pioneering the use of robotics in neuroendovascular procedures, which are performed via the blood vessels of the neck and brain.