Diagnosis and treatment of Chiari malformation and syringomyelia in adults: international consensus document.

BACKGROUND: Syringomyelia and Chiari malformation are classified as rare diseases on Orphanet, but international guidelines on diagnostic criteria and case definition are missing. AIM OF THE STUDY: to reach a consensus among international experts on controversial issues in diagnosis and treatment of Chiari 1 malformation and syringomyelia in adults. METHODS: A multidisciplinary panel of the Chiari and Syringomyelia Consortium (4 neurosurgeons, 2 neurologists, 1 neuroradiologist, 1 pediatric neurologist) appointed an international Jury of experts to elaborate a consensus document. After an evidence-based review and further discussions, 63 draft statements grouped in 4 domains (definition and classification/planning/surgery/isolated syringomyelia) were formulated. A Jury of 32 experts in the field of diagnosis and treatment of Chiari and syringomyelia and patient representatives were invited to take part in a three-round Delphi process. The Jury received a structured questionnaire containing the 63 statements, each to be voted on a 4-point Likert-type scale and commented. Statements with agreement <75% were revised and entered round 2. Round 3 was face-to-face, during the Chiari Consensus Conference (Milan, November 2019). RESULTS: Thirty-one out of 32 Jury members (6 neurologists, 4 neuroradiologists, 19 neurosurgeons, and 2 patient association representatives) participated in the consensus. After round 2, a consensus was reached on 57/63 statements (90.5%). The six difficult statements were revised and voted in round 3, and the whole set of statements was further discussed and approved. CONCLUSIONS: The consensus document consists of 63 statements which benefited from expert discussion and fine-tuning, serving clinicians and researchers following adults with Chiari and syringomyelia.

Is Spreading Depolarization a Risk Factor for Late Epilepsy? A Prospective Study in Patients with Traumatic Brain Injury and Malignant Ischemic Stroke Undergoing Decompressive Craniectomy.

OBJECTIVE: Spreading depolarizations (SDs) have been described in patients with ischemic and haemorrhagic stroke, traumatic brain injury, and migraine with aura, among other conditions. The exact pathophysiological mechanism of SDs is not yet fully established. Our aim in this study was to evaluate the relationship between the electrocorticography (ECoG) findings of SDs and/or epileptiform activity and subsequent epilepsy and electroclinical outcome. METHODS: This was a prospective observational study of 39 adults, 17 with malignant middle cerebral artery infarction (MMCAI) and 22 with traumatic brain injury, who underwent decompressive craniectomy and multimodal neuromonitoring including ECoG in penumbral tissue. Serial electroencephalography (EEG) recordings were obtained for all surviving patients. Functional disability at 6 and 12 months after injury were assessed using the Barthel, modified Rankin (mRS), and Extended Glasgow Outcome (GOS-E) scales. RESULTS: SDs were recorded in 58.9% of patients, being more common-particularly those of isoelectric type-in patients with MMCAI (p < 0.04). At follow-up, 74.7% of patients had epileptiform abnormalities on EEG and/or seizures. A significant correlation was observed between the degree of preserved brain activity on EEG and disability severity (R [mRS]: + 0.7, R [GOS-E, Barthel]: - 0.6, p < 0.001), and between the presence of multifocal epileptiform abnormalities on EEG and more severe disability on the GOS-E at 6 months (R: - 0.3, p = 0.03) and 12 months (R: - 0.3, p = 0.05). Patients with more SDs and higher depression ratios scored worse on the GOS-E (R: - 0.4 at 6 and 12 months) and Barthel (R: - 0.4 at 6 and 12 months) disability scales (p < 0.05). The number of SDs (p = 0.064) and the depression ratio (p = 0.1) on ECoG did not show a statistically significant correlation with late epilepsy. CONCLUSIONS: SDs are common in the cortex of ischemic or traumatic penumbra. Our study suggests an association between the presence of SDs in the acute phase and worse long-term outcome, although no association with subsequent epilepsy was found. More comprehensive studies, involving ECoG and EEG could help determine their association with epileptogenesis.

Performance of glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) biomarkers in predicting CT scan results and neurological outcomes in children with traumatic brain injury (BRAINI-2 paediatric study): protocol of a European prospective multicentre study.

INTRODUCTION: In light of the burden of traumatic brain injury (TBI) in children and the excessive number of unnecessary CT scans still being performed, new strategies are needed to limit their use while minimising the risk of delayed diagnosis of intracranial lesions (ICLs). Identifying children at higher risk of poor outcomes would enable them to be better monitored. The use of the blood-based brain biomarkers glial fibrillar acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) could help clinicians in this decision. The overall aim of this study is to provide new knowledge regarding GFAP and UCH-L1 in order to improve TBI management in the paediatric population. METHODS AND ANALYSIS: We will conduct a European, prospective, multicentre study, the BRAINI-2 paediatric study, in 20 centres in France, Spain and Switzerland with an inclusion period of 30 months for a total of 2880 children and adolescents included. To assess the performance of GFAP and UCH-L1 used separately and in combination to predict ICLs on CT scans (primary objective), 630 children less than 18 years of age with mild TBI, defined by a Glasgow Coma Scale score of 13-15 and with a CT scan will be recruited. To evaluate the potential of GFAP and UCH-L1 in predicting the prognosis after TBI (secondary objective), a further 1720 children with mild TBI but no CT scan as well as 130 children with moderate or severe TBI will be recruited. Finally, to establish age-specific reference values for GFAP and UCH-L1 (secondary objective), we will include 400 children and adolescents with no history of TBI. ETHICS AND DISSEMINATION: This study has received ethics approval in all participating countries. Results from our study will be disseminated in international peer-reviewed journals. All procedures were developed in order to assure data protection and confidentiality. TRIAL REGISTRATION NUMBER: NCT05413499.

Consensus-based recommendations for diagnosis and surgical management of cranioplasty and post-traumatic hydrocephalus from a European panel.

Introduction: Planning cranioplasty (CPL) in patients with suspected or proven post-traumatic hydrocephalus (PTH) poses a significant management challenge due to a lack of clear guidance. Research question: This project aims to create a European document to improve adherence and adapt to local protocols based on available resources and national health systems. Methods: After a thorough non-systematic review, a steering committee (SC) formed a European expert panel (EP) for a two-round questionnaire using the Delphi method. The questionnaire employed a 9-point Likert scale to assess the appropriateness of statements inherent to two sections: "Diagnostic criteria for PTH" and "Surgical strategies for PTH and cranial reconstruction." Results: The panel reached a consensus on 29 statements. In the "Diagnostic criteria for PTH" section, five statements were deemed "appropriate" (consensus 74.2-90.3 %), two were labeled "inappropriate," and seven were marked as "uncertain."In the "Surgical strategies for PTH and cranial reconstruction" section, four statements were considered "appropriate" (consensus 74.2-90.4 %), six were "inappropriate," and five were "uncertain." Discussion and conclusion: Planning a cranioplasty alongside hydrocephalus remains a significant challenge in neurosurgery. Our consensus conference suggests that, in patients with cranial decompression and suspected hydrocephalus, the most suitable diagnostic approach involves a combination of evolving clinical conditions and neuroradiological imaging. The recommended management sequence prioritizes cranial reconstruction, with the option of a ventriculoperitoneal shunt when needed, preferably with a programmable valve. We strongly recommend to adopt local protocols based on expert consensus, such as this, to guide patient care.

Decompressive craniectomy in traumatic brain injury after the DECRA trial. Where do we stand?

PURPOSE OF REVIEW: The results of the multicentre, randomized, controlled trial to test the effectiveness of decompressive craniectomy in adults with traumatic brain injury and high intracranial pressure (Decompressive Craniectomy, DECRA) were published in 2011. DECRA concluded that decompressive craniectomy decreased intracranial pressure (ICP) but was associated with more unfavourable outcomes. Our review aims to put the DECRA trial into context, comment on its findings and discuss whether we should include decompressive craniectomy in our clinical armamentarium. RECENT FINDINGS: The key message that DECRA conveys is that decompressive craniectomy significantly lowers ICP and shortens the length of the stay in the ICU. However, neither mortality nor unfavourable outcome was reduced when adjusting the significant baseline covariates. SUMMARY: The claim that decompressive craniectomy increases unfavourable outcome is overstated and not supported by the data presented in DECRA. We believe it premature to change clinical practice. Given the dismal outcome in these patients, it is reasonable to include this technique as a last resort in any type of protocol-driven management when conventional therapeutic measures have failed to control ICP, the presence of operable masses has been ruled out and the patient may still have a chance of a functional outcome. The main lesson to be learned from this study is that an upper threshold for ICP must be used as a cut-off for selecting decompressive craniectomy candidates.

Transcranial, Non-Invasive Evaluation of Potential Misery Perfusion During Hyperventilation Therapy of Traumatic Brain Injury Patients.

Hyperventilation (HV) therapy uses vasoconstriction to reduce intracranial pressure (ICP) by reducing cerebral blood volume. However, as HV also lowers cerebral blood flow (CBF), it may provoke misery perfusion (MP), in which the decrease in CBF is coupled with increased oxygen extraction fraction (OEF). MP may rapidly lead to the exhaustion of brain energy metabolites, making the brain vulnerable to ischemia. MP is difficult to detect at the bedside, which is where transcranial hybrid, near-infrared spectroscopies are promising because they non-invasively measure OEF and CBF. We have tested this technology during HV (∼30 min) with bilateral, frontal lobe monitoring to assess MP in 27 sessions in 18 patients with traumatic brain injury. In this study, HV did not lead to MP at a group level (p > 0.05). However, a statistical approach yielded 89 events with a high probability of MP in 19 sessions. We have characterized each statistically significant event in detail and its possible relationship to clinical and radiological status (decompressive craniectomy and presence of a cerebral lesion), without detecting any statistically significant difference (p > 0.05). However, MP detection stresses the need for personalized, real-time assessment in future clinical trials with HV, in order to provide an optimal evaluation of the risk-benefit balance of HV. Our study provides pilot data demonstrating that bedside transcranial hybrid near-infrared spectroscopies could be utilized to assess potential MP.

Idiopathic normal pressure hydrocephalus: results of a prospective cohort of 236 shunted patients.

AIM: To describe the outcomes and complication rates in 236 patients with idiopathic normal pressure hydrocephalus (INPH) after treatment. PATIENTS AND METHODS: Among a cohort of 257 patients with suspected INPH, 244 were shunted and 236 were followed up at 6 months after shunting (145 men [61.4%] and 91 women [38.6%] with a median age of 75 years). The study protocol of these patients included clinical, radiological, neuropsychological and functional assessment. The decision to shunt patients was based on continuous intracranial pressure monitoring and CSF dynamics studies. A differential low-pressure valve system, always combined with a gravity compensating device, was implanted in 99% of the patients. RESULTS: After shunting, 89.9% of the patients showed clinical improvement (gait improved in 79.3% of patients, sphincter control in 82.4%, and dementia in 63.7%). Two patients (0.8%) died. Early postsurgical complications were found in 13 of the 244 shunted patients (5.3%). Six months after shunting, the follow-up CT showed asymptomatic hygromas in 8 of the 236 (3.4%). Additional postsurgical complications were found in 7 patients (3%), consisting of 6 subdural hematomas (3 acute and 3 chronic) and 1 distal catheter infection. CONCLUSIONS: Currently, a high percentage of patients with INPH can improve after shunting, with early and late complication rates of less than 12%.

Normal hypocretin-1 (orexin A) levels in cerebrospinal fluid in patients with idiopathic intracranial hypertension.

AIM: Low levels of hypocretin-1 (HC-1) have been associated with hypersomnia, obesity, depression, and chronic headaches. These conditions are frequently present in patients with idiopathic intracranial hypertension (IIH) and may be associated with abnormalities of the hypocretin system. The aim of this study was to determine HC-1 concentrations in cerebrospinal fluid (CSF) in a series of patients with IIH and to compare these concentrations with those in a control group with no neurological alterations. PATIENTS AND METHODS: This prospective study included a cohort of 26 consecutive patients with IIH who were mostly women (25 vs. 1) with a mean age of 42.5 ± 13.2. CSF samples were obtained from a lumbar puncture performed between 08:00 and 10:00 a.m. HC-1 was determined by a competitive radioimmunoassay (RIA) using I(125) as the isotope. Samples of normal CSF were obtained during spinal anesthesia for urological, general or vascular surgery from 40 patients (10 women and 30 men with a mean age of 63.7 ± 14.8) with no previous neurological or psychiatric history, a normal neurological examination, and MMSE scores of ≥ 24. RESULTS: No statistically significant differences were found between HC-1 levels in the CSF of patients with IIH (119.61 ± 21.63 pg/mL) and those of the control group (119.07 ± 20.30 pg/mL; p = 0.918). CONCLUSIONS: HC-1 is not associated with the clinical symptoms present in patients with IIH.

How to Choose a Shunt for Patients with Normal Pressure Hydrocephalus: A Short Guide to Selecting the Best Shunt Assembly.

Most patients with hydrocephalus are still managed with the implantation of a cerebrospinal fluid (CSF) shunt in which the CSF flow is regulated by a differential-pressure valve (DPV). Our aim in this review is to discuss some basic concepts in fluid mechanics that are frequently ignored but that should be understood by neurosurgeons to enable them to choose the most adequate shunt for each patient. We will present data, some of which is not provided by manufacturers, which may help neurosurgeons in selecting the most appropriate shunt. To do so, we focused on the management of patients with idiopathic "normal-pressure hydrocephalus" (iNPH), as one of the most challenging scenarios, in which the combination of optimal technology, patient characteristics, and knowledge of fluid mechanics can significantly modify the surgical results. For a better understanding of the available hardware and its evolution over time, we will have a second look at the design of the first DPV and the reasons why additional devices were incorporated to control for shunt overdrainage and its related complications. We try to persuade the reader that a clear understanding of the physical concepts of the CSF and shunt dynamics is key to understand the pathophysiology of iNPH and to improve its treatment.

Kir6.2, the Pore-Forming Subunit of ATP-Sensitive K+ Channels, Is Overexpressed in Human Posttraumatic Brain Contusions.

Brain contusions (BCs) are one of the most frequent lesions in patients with moderate and severe traumatic brain injury (TBI). BCs increase their volume due to peri-lesional edema formation and/or hemorrhagic transformation. This may have deleterious consequences and its mechanisms are still poorly understood. We previously identified de novo upregulation sulfonylurea receptor (SUR) 1, the regulatory subunit of adenosine triphosphate (ATP)-sensitive potassium (KATP) channels and other channels, in human BCs. Our aim here was to study the expression of the pore-forming subunit of KATP, Kir6.2, in human BCs, and identify its localization in different cell types. Protein levels of Kir6.2 were detected by western blot (WB) from 33 contusion specimens obtained from 32 TBI patients aged 14-74 years. The evaluation of Kir6.2 expression in different cell types was performed by immunofluorescence in 29 contusion samples obtained from 28 patients with a median age of 42 years. Control samples were obtained from limited brain resections performed to access extra-axial skull base tumors or intraventricular lesions. Contusion specimens showed an increase of Kir6.2 expression in comparison with controls. Regarding cellular location of Kir6.2, there was no expression of this channel subunit in blood vessels, either in control samples or in contusions. The expression of Kir6.2 in neurons and microglia was also analyzed, but the observed differences were not statistically significant. However, a significant increase of Kir6.2 was found in glial fibrillary acidic protein (GFAP)-positive cells in contusion specimens. Our data suggest that further research on SUR1-regulated ionic channels may lead to a better understanding of key mechanisms involved in the pathogenesis of BCs, and may identify novel targeted therapeutic strategies.

Migració de la vàlvula de derivació ventriculoperitoneal a l’escrot / Migración de la válvula de derivación ventriculoperitoneal al escroto / Ventriculoperitoneal shunt valve migration into the scrotum

Introducció. La migració de la vàlvula de derivació ventriculoperitoneal (VDVP) és una complicació infreqüent, i quan es produeix a l’escrot és excepcional. Es presenta un cas de migració escrotal de la VDVP. Cas clínic. Lactant de sexe masculí amb antecedents de prematuritat i acondroplàsia, a qui es va col·locar una VDVP quan tenia un mes de vida. Al cap d’un mes de la cirurgia, acudeix a urgències per irritabilitat i augment de volum escrotal dret. Se li fa una radiografia que objectiva el catèter distal de la VDVP a la zona inguinal, i es confirma la migració escrotal del catèter. No presenta simptomatologia de disfunció valvular. Als tres mesos d’edat, mitjançant abordatge laparoscòpic, es tanca la persistència del conducte peritoneovaginal de manera percutània. Posteriorment no presenta complicacions inguinoescrotals durant un seguiment de 13 mesos. Comentari. En un pacient pediàtric prematur portador de VDVP, cal sospitar la persistència del conducte peritoneovaginal. Les troballes més freqüents són l’hidrocele i l’hèrnia inguinal, però també s’han descrit casos de migració escrotal de la VDVP. La migració escrotal es diagnostica per la troballa radiològica del catèter a la zona inguinal, i el tractament és el tancament del conducte peritoneovaginal. (AU)

Introducción. La migración de la válvula de derivación ventriculoperitoneal (VDVP) es una complicación infrecuente, y cuando se produce en el escroto es excepcional. Se presenta un caso de migración escrotal de la VDVP. Caso clínico. Lactante varón con antecedentes de prematuridad y acondroplasia, a quien se colocó una VDVP cuando tenía un mes de vida. Al mes de la cirugía acude a urgencias por irritabilidad y aumento de tamaño escrotal derecho. Se realiza una radiografía que objetiva el catéter de la VDVP a nivel inguinal, confirmando la migración escrotal del catéter. No presenta sintomatología de disfunción valvular. A los tres meses de edad, mediante abordaje laparoscópico, se realiza el cierre de la persistencia del conducto peritoneovaginal de manera percutánea. Posteriormente no presenta complicaciones inguinoescrotales durante un seguimiento de 13 meses. Comentario. En un paciente pediátrico portador de VDVP, se debe sospechar la persistencia del conducto peritoneovaginal. Los hallazgos más frecuentes son el hidrocele y la hernia inguinal, pero también se han descrito casos de migración escrotal de la VDVP. La migración escrotal se diagnostica por el hallazgo radiológico del catéter a nivel inguinal, y su tratamiento es el cierre del conducto peritoneovaginal. (AU)

Introduction. Ventriculoperitoneal shunt (VPS) valve migration is an infrequent complication, and when it occurs to the scrotum is exceptional. A case of scrotal migration of the VPS valve is presented. Case report. A male infant with a history of prematurity and achondroplasia underwent VPS placement at one month of age. One month after the surgery, he was seen in the Emergency Room due to irritability and increased right scrotal size. An X-ray showed the tip of the VPS catheter at the inguinal level, confirming the scrotal migration. Symptoms of valve dysfunction were not present. At three months of age, percutaneously closure of the persistent peritoneovaginal duct was performed laparoscopically, with no additional complications recorded at a 13-month follow-up. Comments. The persistence of the peritoneovaginal duct must always be considered in children with VPS. The most frequent findings are hydrocele and inguinal hernia, but cases of scrotal migration have also been described. Scrotal migration of the VPS can be diagnosed by the radiological finding of the tip of the catheter at the inguinal level, and treatment is the closure of the peritoneovaginal duct. (AU)

Functional and magnetic resonance imaging correlates of corpus callosum in normal pressure hydrocephalus before and after shunting.

BACKGROUND: Normal pressure hydrocephalus (NPH) is associated with corpus callosum abnormalities. OBJECTIVES: To study the clinical and neuropsychological effect of callosal thinning in 18 patients with idiopathic NPH and to investigate the postsurgical callosal changes in 14 patients. METHODS: Global corpus callosum size and seven callosal subdivisions were measured. Neuropsychological assessment included an extensive battery assessing memory, psychomotor speed, visuospatial and frontal lobe functioning. RESULTS: After surgery, patients showed improvements in memory, visuospatial and frontal lobe functions, and psychomotor speed. Two frontal corpus callosum areas, the genu and the rostral body, were the regions most related to the clinical and neuropsychological dysfunction. After surgery, total corpus callosum and four of the seven subdivisions presented a significant increase in size, which was related to poorer neuropsychological and clinical outcome. CONCLUSION: The postsurgical corpus callosum increase might be the result of decompression, re-expansion and increase of interstitial fluid, although it may also be caused by differences in shape due to cerebral reorganisation.

Post-surgical changes in brain metabolism detected by magnetic resonance spectroscopy in normal pressure hydrocephalus: results of a pilot study.

BACKGROUND: Adult normal pressure hydrocephalus (NPH) is one of the few potentially treatable causes of dementia. Some morphological and functional abnormalities attributed to hydrocephalus improve following treatment. OBJECTIVES: We focused on analysis of changes in cerebral metabolites using proton magnetic resonance spectroscopy (1H-MRS) after NPH treatment, and its clinical and cognitive correlation. METHODS: 1H-MRS, neuropsychological and clinical status examinations were performed before and 6 months after shunting in 12 adults with idiopathic NPH. We obtained N-acetyl-aspartate (NAA), choline (Cho), myoinositol (MI) and creatine (Cr) values. RESULTS: After surgery, NAA/Cr was significantly increased. Moreover, NAA/Cr values were related to cognitive deterioration. CONCLUSION: MRS could be a marker of neuronal dysfunction in NPH.

Is intracranial pressure monitoring in the epidural space reliable? Fact and fiction.

OBJECT: Epidural pressures have been reported as being systematically higher than ventricular fluid pressures. These discrepancies have been attributed both to the characteristics of the sensor and to the particular anatomy of the epidural space. To determine which of these two possible causes better explains higher epidural readings, the authors compared pressure values obtained during simultaneous epidural and lumbar pressure monitoring in 53 patients and during simultaneous subdural and lumbar pressure monitoring in 22 patients. The same nonfluid coupled sensor device was used in all compartments. METHODS: All 75 patients had normal craniospinal communication. Simultaneous intracranial and lumbar readings were performed every 30 seconds. The epidural-lumbar and subdural-lumbar pressure values were compared using correlation analysis and the Bland-Altman method. The median differences in initial epidural-lumbar and subdural-lumbar pressure values were 11 mm Hg (interquartile range 2-24 mm Hg) and 0 mm Hg (interquartile range -2 to 1 mm Hg), respectively. The correlation coefficients of the mean epidural-lumbar and subdural-lumbar intracranial pressure (ICP) values were p = 0.48 (p < 0.001) and p = 0.88 (p < 0.001), respectively. Using the Bland-Altman analysis, epidural-lumbar methods showed a mean difference of -20.93 mm Hg; epidural pressure values were systematically higher than lumbar values, and these discrepancies were greater with higher ICP values. Subdural-lumbar methods showed a mean difference of 0.35 mm Hg and both were equally valid with all mean ICP values. CONCLUSIONS: Epidural ICP monitoring produces artifactually high values. These values are not related to the type of sensor used but to the specific characteristics of the epidural intracranial space.

Cephalometric oropharynx and oral cavity analysis in Chiari malformation Type I: a retrospective case-control study.

OBJECTIVE Traditionally, Chiari malformation Type I has been related to downward herniation of the cerebellar tonsils as a consequence of an underdeveloped posterior cranial fossa. Although the common symptoms of Chiari malformation Type I are occipital headaches, cervical pain, dizziness, paresthesia, and sensory loss, patients often report symptoms related to pharyngeal dysfunction such as choking, regurgitation, dysphagia, aspiration, chronic cough, and sleep disorders. In addition, tracheal intubation is often difficult in these patients. The purpose of this study was to analyze the morphological features of the oropharynx and oral cavity in patients with Chiari malformation Type I to help identify underlying anatomical anomalies leading to these debilitating symptoms. METHODS Seventy-six adult patients with symptomatic Chiari malformation Type I with cerebellar tonsillar descent greater than 5 mm below the foramen magnum and a small posterior cranial fossa and 49 sex-matched controls were selected to perform a retrospective case-control MRI-based morphometric study in a tertiary hospital. Eleven linear and areal parameters of the oropharyngeal cavity on midsagittal T1-weighted MRI were measured and the average values between patients and control cohorts were compared. Correlations between variables showing or approaching statistical significance in these structures and posterior cranial fossa measurements related with the occipital bone were sought. RESULTS Significant differences were detected for several oropharynx and oral cavity measures in the patient cohort, primarily involving the length and thickness of the soft palate (p = 9.5E-05 and p = 3.0E-03, respectively). A statistically significant (p < 0.01) moderate correlation between some of these variables and posterior cranial fossa parameters was observed. CONCLUSIONS The existence of structural oropharyngeal and oral cavity anomalies in patients with Chiari malformation Type I was confirmed, which may contribute to the frequent occurrence of respiratory and deglutitory complications and sleep disorders in this syndrome.

Reappraisal of the reference levels for energy metabolites in the extracellular fluid of the human brain.

Cerebral microdialysis is widely used in neurocritical care units. The goal of this study was to establish the reference interval for the interstitial fluid concentrations of energy metabolites and glycerol by using the extrapolation to zero-flow methodology in anesthetized patients and by constant perfusion at 0.3 µL/min in awake patients. A CMA-71 probe was implanted during surgery in normal white matter of patients with posterior fossa or supratentorial lesions, and the perfusion flow rate was randomized to 0.1, 0.3, 0.6, 1.2, and 2.4 µL/min. Within 24 h of surgery, perfusion was restarted at a constant 0.3 µL/min in fully awake patients. The actual interstitial fluid metabolite concentrations were calculated using the zero-flow methodology. In vitro experiments were also conducted to evaluate the reproducibility of the in vivo methodology. Nineteen patients (seven males) with a median age of 44 years (range: 21-69) were included in the in vivo study. The median (lower-upper) reference interval values were 1.57 (1.15-4.13 mmol/L) for glucose, 2.01 (1.30-5.31 mmol/L) for lactate, 80.0 (54.4-197.0 µmol/L) for pyruvate, and 49.9 (23.6-227.3 µmol/L) for glycerol. The reference intervals reported raises the need to reconsider traditional definitions of brain metabolic disturbances and emphasize the importance of using different thresholds for awake patients and patients under anesthesia.

Characterization of the Ionic Profile of the Extracellular Space of the Injured and Ischemic Brain: A Microdialysis Study.

Traumatic brain injury (TBI) and ischemic stroke cause a variable disruption of ionic homeostasis and massive ionic fluxes with subsequent osmotic water movement across the cells that causes edema, brain swelling, and deformation of the damaged tissue. Although cerebral microdialysis (CMD) has been used to study the brain neurochemistry, the ionic profiles of brain interstitial space fluid have rarely been reported in humans. We studied the ionic profile in injured areas of the brain by using CMD. As a control group, we included seven patients who had undergone surgical treatment of posterior fossa lesions, without abnormalities in the supratentorial compartment. Inductively coupled plasma mass spectrometry (ICP-MS) was used for ion determination. No significant differences were found in the [Na+]o, [K+]o, and [Cl-]o between normal injured brains and controls. The ionic profile of the ischemic core was characterized by very high [K+]o and an increase in [Na+]o, whereas [Cl-]o was linearly related to [Na+]o. In the traumatic core (TC), significantly higher levels of [Na+]o, [Cl-]o, and [K+]o were found. The main finding in the penumbra was a completely normal ionic profile for [Na+]o and [K+]o in 60% of the samples. ICP-MS coupled to ionic assays creates a powerful tool for a better understanding of the complex ionic disturbances that occur after severe TBI and ischemic stroke.

Does Normobaric Hyperoxia Cause Oxidative Stress in the Injured Brain? A Microdialysis Study Using 8-Iso-Prostaglandin F2α as a Biomarker.

Significant controversy exists regarding the potential clinical benefit of normobaric hyperoxia (NBO) in patients with traumatic brain injury (TBI). This study consisted of two aims: 1) to assess whether NBO improves brain oxygenation and metabolism and 2) to determine whether this therapy may increase the risk of oxidative stress (OxS), using 8-iso-Prostaglandin F2α (PGF2α) as a biomarker. Thirty-one patients with a median admission Glasgow Coma Scale score of 4 (min: 3, max: 12) were monitored with cerebral microdialysis and brain tissue oxygen sensors and treated with fraction of inspired oxygen (FiO2) of 1.0 for 4 h. Patients were divided into two groups according to the area monitored by the probes: normal injured brain and traumatic penumbra/traumatic core. NBO maintained for 4 h did not induce OxS in patients without preOxS at baseline, except in one case. However, for patients in whom OxS was detected at baseline, NBO induced a significant increase in 8-iso-PGF2α. The results of our study showed that NBO did not change energy metabolism in the whole group of patients. In the five patients with brain lactate concentration ([Lac]brain) > 3.5 mmol/L at baseline, NBO induced a marked reduction in both [Lac]brain and lactate-to-pyruvate ratio. Although these differences were not statistically significant, together with the results of our previous study, they suggest that TBI patients would benefit from receiving NBO when they show indications of disturbed brain metabolism. These findings, in combination with increasing evidence that TBI metabolic crises are common without brain ischemia, open new possibilities for the use of this accessible therapeutic strategy in TBI patients.

Corpus callosum functioning in patients with normal pressure hydrocephalus before and after surgery.

OBJECTIVES: Our aim was to evaluate corpus callosum functioning in a group of patients with normal pressure hydrocephalus (NPH) before and after shunting. METHODS: Left ear-extinction under a dichotic listening task was evaluated in twenty-three patients with NPH, 30 patients with Alzheimer's disease and 30 aged controls. RESULTS: Patients with NPH had higher levels of left ear extinction than the control and Alzheimer's groups. Sixty-one percent of NPH patients exhibited left ear suppression, compared with 13% of Alzheimer's patients and 17% of controls. Following surgery, NPH patients showed a significant change in the degree of asymmetry in the dichotic listening task. CONCLUSIONS: Hydrocephalus was associated with left-ear extinction,which diminished after surgery. Our results may indicate reversible functional damage in the corpus callosum.