Decompressive craniectomy in children: indications and outcome from a tertiary centre.

INTRODUCTION: The role of decompressive craniectomy (DC) is as a rescue therapy for the treatment of intracranial hypertension. The indications for the DC are variable. METHODS: The clinical details, imaging, operative findings and follow-up data of children less than or equal to 18 years of age were reviewed for more information on the children who underwent DC in the last 5 years. RESULTS: During the study period, a total of 128 children underwent DC. The trauma cases were 66, and the non-trauma cases were 62. The common indication for DC was pure acute subdural hematoma 33 (50%), followed by contusion 10 (15%) in the trauma group, and in non-trauma, arterial infarction in 20 (32%) and cerebral venous thrombosis in 17 (27%). Hemicraniectomy was done in 114 (89%), and bifrontal craniectomy was done in 7 (5.4%) cases. The median duration follow-up was 7 months in non-trauma and 6 months in trauma. GCS was less than 8, the motor score was less than 3, and pupillary asymmetry, hypotension and basal cistern effacement were factors related to an unfavourable outcome in the non-trauma group. In regression analysis, only a motor score of less than three was associated with the non-trauma group. Age less than 10 years, GCS less than 8, motor score less than three and preoperative infarction were the predictive factors in univariate analysis, and only GCS less than 8 was the predictive factor for unfavourable factors in regression analysis in the trauma group. CONCLUSION: The DC is performed as a lifesaving procedure. The unfavourable outcome is slightly higher in non-trauma cases compared to trauma cases. However, the mortality rate is high in trauma cases.

Impaired cerebrospinal fluid transport due to idiopathic subdural hematoma in pig: an unusual case.

BACKGROUND: We report the effects of the presentation of an idiopathic subdural hematoma (SDH) in an adult domestic pig on the glymphatic system, a brain-wide solute clearance system. This accidental finding is based on our recently published study that described this system for the first time in large mammals. Our current results define the need to investigate cerebrovascular pathologies that could compromise glymphatic function in gyrencephalic animal models as a tool to bridge rodent and human glymphatic studies. CASE PRESENTATION: The pig underwent intracisternal infusion of a fluorescent tracer under general anesthesia to delineate cerebrospinal fluid (CSF) pathways, and was euthanized at the end of 3 h of tracer circulation. During brain isolation, a hematoma measuring approximately 15 × 35 mm in size beneath the dura was evident overlying fronto-parietal brain surface. Interestingly, CSF tracer distribution was markedly reduced on dorsal, lateral and ventral surfaces of the brain when compared with a control pig that was infused with the same tracer. Furthermore, regional distribution of tracer along the interhemispheric fissure, lateral fissure and hippocampus was 4-5-fold reduced in comparison with a control pig. Microscopically, glial-fibrillary acidic protein and aquaporin-4 water channel immunoreactivities were altered in the SDH pig brain. CONCLUSIONS: This is the first case of impaired glymphatic pathway due to an idiopathic SDH in a pig. Potential etiology could involve an acceleration-deceleration injury inflicted prior to arrival at our housing facility (e.g., during animal transportation) leading to disruption of bridging veins along the superior sagittal sinus and impairing CSF pathways in the whole brain. This accidental finding of globally impaired glymphatic function sheds light on a novel consequence of SDH, which may play a role in the enhanced cognitive decline seen in elderly presenting with chronic SDH.

Direct Cannula Implantation in the Cisterna Magna of Pigs.

The glymphatic system is a waste clearance system in the brain that relies on the flow of cerebrospinal fluid (CSF) in astrocyte-bound perivascular spaces and has been implicated in the clearance of neurotoxic peptides such as amyloid-beta. Impaired glymphatic function exacerbates disease pathology in animal models of neurodegenerative diseases, such as Alzheimer's, which highlights the importance of understanding this clearance system. The glymphatic system is often studied by cisterna magna cannulations (CMc), where tracers are delivered directly into the cerebrospinal fluid (CSF). Most studies, however, have been carried out in rodents. Here, we demonstrate an adaptation of the CMc technique in pigs. Using CMc in pigs, the glymphatic system can be studied at a high optical resolution in gyrencephalic brains and in doing so bridges the knowledge gap between rodent and human glymphatics.

Glymphatic pathways in the gyrencephalic brain.

Identification of the perivascular compartment as the point of exchange between cerebrospinal fluid (CSF) and interstitial fluid mediating solute clearance in the brain, named the glymphatic system, has emerged as an important clearance pathway for neurotoxic peptides such as amyloid-beta. However, the foundational science of the glymphatic system is based on rodent studies. Here we investigated whether the glymphatic system exists in a large mammal with a highly gyrified brain. CSF penetration into the brain via perivascular pathways, a hallmark of glymphatic function, was seen throughout the gyrencephalic cortex and subcortical structures, validating the conservation of the glymphatic system in a large mammal. Macroscopic CSF tracer distribution followed the sulci and fissures showing that these folds enhance CSF dispersion. Three-dimensional renditions from light sheet microscopy showed a PVS influx density 4-fold larger in the pig brain than in mice. This demonstrates the existence of an advanced solute transport system in the gyrencephalic brain that could be utilised therapeutically for enhancing waste clearance.

Achieving brain clearance and preventing neurodegenerative diseases-A glymphatic perspective.

Age-related neurodegenerative diseases are a growing burden to society, and many are sporadic, meaning that the environment, diet and lifestyle play significant roles. Cerebrospinal fluid (CSF)-mediated clearing of brain waste products via perivascular pathways, named the glymphatic system, is receiving increasing interest, as it offers unexplored perspectives on understanding neurodegenerative diseases. The glymphatic system is involved in clearance of metabolic by-products such as amyloid-ß from the brain, and its function is believed to lower the risk of developing some of the most common neurodegenerative diseases. Here, we present magnetic resonance imaging (MRI) data on the heart cycle's control of CSF flow in humans which corroborates findings from animal studies. We also review the importance of sleep, diet, vascular health for glymphatic clearance and find that these factors are also known players in brain longevity.

Differential regulation of oxidative stress, microbiota-derived, and energy metabolites in the mouse brain during sleep.

Sleep has evolved as a universal core function to allow for restorative biological processes. Detailed knowledge of metabolic changes necessary for the sleep state in the brain is missing. Herein, we have performed an in-depth metabolic analysis of four mouse brain regions and uncovered region-specific circadian variations. Metabolites linked to oxidative stress were altered during sleep including acylcarnitines, hydroxylated fatty acids, phenolic compounds, and thiol-containing metabolites. These findings provide molecular evidence of a significant metabolic shift of the brain energy metabolism. Specific alterations were observed for brain metabolites that have previously not been associated with a circadian function including the microbiome-derived metabolite ergothioneine that suggests a regulatory function. The pseudopeptide ß-citryl-glutamate has been linked to brain development and we have now discovered a previously unknown regioisomer. These metabolites altered by the circadian rhythm represent the foundation for hypothesis-driven studies of the underlying metabolic processes and their function.

When the Bone Flap Expands Like Bellows of Accordion: Feasibility Study Using Novel Technique of Expansile (Hinge) Craniotomy for Severe Traumatic Brain Injury.

BACKGROUND: Decompressive craniectomy (DC) is a rescue operation performed for reduction of intracranial pressure due to progressive brain swelling, mandating the need for cranioplasty. OBJECTIVE: To describe expansile craniotomy (EC) as a noninferior technique that may be effectively utilized in situations requiring standard DC. MATERIALS AND METHODS: A decision to perform DC or EC was taken by consecutively allocation to either of the procedures. The bone flap was divided into three pieces, which were tied loosely to each other and to the skull using silk threads. The primary outcome included functional assessment using Glasgow outcome scale (GOS) score at 1 year. RESULTS AND CONCLUSIONS: Total 67 patients were included in the analyses, of which, 31 underwent EC and 36 underwent DC. Both the cohorts were matched in terms of baseline determinants for age, Glasgow coma scale, and Rotterdam score at admission. There was no significant difference in GOS scores and the extent of volume expansion obtained by EC as compared to DC. Complication rates though less in EC group did not differ significantly between the groups. EC appears to be the safe and effective alternative to DC in the management of brain swelling due to TBI with a potential to obviate the need of cranioplasty.

Light sheet fluorescence microscopy of optically cleared brains for studying the glymphatic system.

Fluid transport in the perivascular space by the glia-lymphatic (glymphatic) system is important for the removal of solutes from the brain parenchyma, including peptides such as amyloid-beta which are implicated in the pathogenesis of Alzheimer's disease. The glymphatic system is highly active in the sleep state and under the influence of certain of anaesthetics, while it is suppressed in the awake state and by other anaesthetics. Here we investigated whether light sheet fluorescence microscopy of whole optically cleared murine brains was capable of detecting glymphatic differences in sleep- and awake-mimicking anaesthesia, respectively. Using light-sheet imaging of whole brains, we found anaesthetic-dependent cerebrospinal fluid (CSF) influx differences, including reduced tracer influx along tertiary branches of the middle cerebral artery and reduced influx along dorsal and anterior penetrating arterioles, in the awake-mimicking anaesthesia. This study establishes that light sheet microscopy of optically cleared brains is feasible for quantitative analyses and can provide images of the entire glymphatic system in whole brains.

Role of Decompressive Craniectomy in the Management of Cerebral Venous Sinus Thrombosis.

Cerebral venous sinus thrombosis (CVST) is a relatively uncommon cause of stroke more often affecting women and younger individuals. Blockage of the venous outflow rapidly causes edema and space-occupying venous infarctions and it seems intuitive that decompressive craniectomy (DC) can effectively reduce intracranial pressure just like it works for malignant middle cerebral artery infarcts and traumatic brain injury. But because of the relative rarity of this type of stroke, strong evidence from randomized controlled trials that DC is a life-saving procedure is not available unlike in the latter two conditions. There is a possibility that other forms of interventions like endovascular recanalization, thrombectomy, thrombolysis, and anticoagulation, which cannot be used in established middle cerebral artery infarcts and TBI, can reverse the ongoing pathology of increasing edema in CVST. Such interventions, although presently unproven, could theoretically obviate the need for DC when used in early stages. However, in the absence of such evidence, we recommend that DC be considered early as a life-saving measure whenever there are large hemorrhagic infarcts, expanding edema, radiological, and clinical features of impending herniation. This review gives an overview of the etiology and risk factors of CVST in different patient populations and examines the effectiveness of DC and other forms of interventions.

Neurotrauma Care Delivery in a Limited Resource Setting-Lessons Learned From Referral and Patient Flow in a Tertiary Care Center.

BACKGROUND: With the increasing population, motorization, and road traffic accidents, neurotrauma has been increasing in India. Inadequate triage and underusage of locally available resources at all healthcare levels has led to nonuniform neurotrauma care delivery. We present our experience at a tertiary care hospital. We evaluated the referral pattern of mild traumatic brain injury (mTBI) cases to enable adequate care to patients with moderate and severely injured TBI. METHODS: All patients with head injury (n = 3891) referred to the emergency department of our institution during a 4-month period were evaluated. The demographic characteristics, ambulance usage, and time management during in-hospital patient flow were evaluated using the Lean Six Sigma approach. We have also provided solutions for optimal usage of available resources. RESULTS: Patients with mTBI comprised 77% of head injury referrals. Of all the patients referred from peripheral hospitals, 48% had normal head computed tomography (CT) scan findings. The CT waiting and lead (arrival-to-discharge) times were 35 ± 44 minutes and 114 minutes, respectively. No clinical to radiological correlation was found between the head CT scan findings and a decision to refer a patient to our institute. Only 10% of the patients with abnormal head CT scans (41%) required neurosurgical intervention. The mean duration from CT imaging to the initiation of surgery was 192.7 ± 172.1 minutes. CONCLUSIONS: Most of the patients with mTBI were referred to a tertiary care center, leading to secondary overtriage and overburdening of the existing resources at a specialized care hospital, possibly owing to ineffective triage at the primary and secondary healthcare centers. This would limit the adequate management of moderate to severe TBI cases in such a hospital.

Complications of Decompressive Craniectomy.

Decompressive craniectomy (DC) has become the definitive surgical procedure to manage medically intractable rise in intracranial pressure due to stroke and traumatic brain injury. With incoming evidence from recent multi-centric randomized controlled trials to support its use, we could expect a significant rise in the number of patients who undergo this procedure. Although one would argue that the procedure reduces mortality only at the expense of increasing the proportion of the severely disabled, what is not contested is that patients face the risk of a large number of complications after the operation and that can further compromise the quality of life. Decompressive craniectomy (DC), which is designed to overcome the space constraints of the Monro Kellie doctrine, perturbs the cerebral blood, and CSF flow dynamics. Resultant complications occur days to months after the surgical procedure in a time pattern that can be anticipated with advantage in managing them. New or expanding hematomas that occur within the first few days can be life-threatening and we recommend CT scans at 24 and 48 h postoperatively to detect them. Surgeons should also be mindful of the myriad manifestations of peculiar complications like the syndrome of the trephined and neurological deterioration due to paradoxical herniation which may occur many months after the decompression. A sufficiently large frontotemporoparietal craniectomy, 15 cm in diameter, increases the effectiveness of the procedure and reduces chances of external cerebral herniation. An early cranioplasty, as soon as the brain is lax, appears to be a reasonable choice to mitigate many of the late complications. Complications, their causes, consequences, and measures to manage them are described in this chapter.

Symptomatic Thoracic Nerve Root Herniation into an Extradural Arachnoid Cyst: Case Report and Review of the Literature.

BACKGROUND: Spinal extradural arachnoid cysts (SEACs) are relatively rare and usually asymptomatic. They preferentially are situated in the thoracic extradural space and almost always dorsal. SEACs may present with back pain and/or cord compression symptoms. Needle aspiration, needle fenestration, or open surgical resection/fenestration have been reported as treatment modalities. CASE DESCRIPTION: We present a 35-year-old woman who complained of radiating pain from the right lower thoracic region of her back toward the right inguinal region, which was aggravated upon defecation and straining. Magnetic resonance imaging (MRI) revealed an extradural cyst located laterally at T11-T12 level on the right, with a nerve root herniation. During a T11-T12 hemilaminectomy, on resection of the cyst wall, a nerve root was noted to be herniating into the cyst cavity through a dural defect. The nerve root was released and repositioned intradurally, followed by direct suture of the dural tear. Histologic findings of the cyst wall confirmed an arachnoid cyst. Postoperative course was uneventful without complications. Postoperative MRI confirmed a complete resection of the cyst. Five years after surgery, the patient is asymptomatic with complete recovery. CONCLUSIONS: Thoracic SEACs can present with radiating pain due to a transdural herniation of a thoracic nerve root into the cyst, potentially due to a mechanism of intermittent pressure gradients between the intradural and extradural spaces. MRI can prove beneficial in visualizing the nerve prolapsing into the cyst. Open resection of the cyst wall, reduction of the nerve root herniation, and subsequent direct closure of the dural tear led to complete recovery.

Long-term survival in permanent middle cerebral artery occlusion: a model of malignant stroke in rats.

Occlusion of the middle cerebral artery (MCA) by an intraluminal filament is widely used to study focal brain ischemia in male Sprague-Dawley rats. However, permanent occlusion goes along with a high fatality. To overcome this drawback we designed a new filament carrying a bowling pin-shaped tip (BP-tip) and compared this with three conventionally tipped filaments. Follow-up periods were 24 h (all groups) and 72 and 120 h in BP-tip group. Ischemic damage and swelling were quantified using silver nitrate staining. Collateral flow via the posterior cerebral artery (PCA) was assessed using selective dye perfusion of the internal carotid artery. Despite a comparable decrease of brain perfusion in all groups, ischemic damage was significantly smaller in BP-tips (p < 0.05). Moreover, BP-tip significantly reduced mortality from 60% to 12.5% and widely spared the occipital region and hypothalamus from ischemic damage. Conventional but not BP-tip filaments induced vascular distortion, measured as gross displacement of the MCA origin, which correlated with occipital infarction size. Accordingly, BP-tip occluded rats showed a significantly better collateral filling of the PCA territory. Ischemic volume significantly increased in BP-tip occlusion at 72 h follow-up. BP-tip filaments offer superior survival in permanent MCA occlusion, while mimicking the course of a malignant stroke in patients.

First in vivo potassium-39 (³9K) MRI at 9.4 T using conventional copper radio frequency surface coil cooled to 77 K.

Potassium-39 ((39)K) magnetic resonance imaging (MRI) is a noninvasive technique which could potentially allow for detecting intracellular physiological variations in common human pathologies such as stroke and cancer. However, the low signal-to-noise ratio (SNR) achieved in (39)K-MR images hampered data acquisition with sufficiently high spatial and temporal resolution in animal models so far. Full wave electromagnetic (EM) simulations were performed for a single-loop copper (Cu) radio frequency (RF) surface resonator with a diameter of 30 mm optimized for rat brain imaging at room temperature (RT) and at liquid nitrogen (LN2) with a temperature of 77 K. A novel cryogenic Cu RF surface resonator with home-built LN2 nonmagnetic G10 fiberglass cryostat system for small animal scanner at 9.4 T was designed, built and tested in phantom and in in vivo MR measurements. Aerogel was used for thermal insulation in the developed LN2 cryostat. In this paper, we present the first in vivo (39)K-MR images at 9.4 T for both healthy and stroke-induced rats using the developed cryogenic coil at 77 K. In good agreement with EM-simulations and bench-top measurements, the developed cryogenic coil improved the SNR by factor of 2.7 ± 0.2 in both phantom and in in vivo MR imaging compared with the same coil at RT.

Neurovascular protection by targeting early blood-brain barrier disruption with neurotrophic factors after ischemia-reperfusion in rats*.

The 'new penumbra' concept imbues the transition between injury and repair at the neurovascular unit with profound implications for selecting the appropriate type and timing of neuroprotective interventions. In this conceptual study, we investigated the protective effects of pigment epithelium-derived factor (PEDF) and compared them with the properties of epidermal growth factor (EGF) in a rat model of ischemia-reperfusion injury. We initiated a delayed intervention 3 hours after reperfusion using equimolar amounts of PEDF and EGF. These agents were then administered intravenously for 4 hours following reperfusion after 1 hour of focal ischemia. Magnetic resonance imaging indices were characterized, and imaging was performed at multiple time points post reperfusion. PEDF and EGF reduced lesion volumes at all time points as observed on T2-weighted images (T2-LVs). In addition PEDF selectively attenuated lesion volume expansion at 48 hours after reperfusion and persistently modulated blood-brain barrier (BBB) permeability at all time points. Intervention with peptides is suspected to cause edema formation at distant regions. The observed T2-LV reduction and BBB modulation by these trophic factors is probably mediated through a number of diverse mechanisms. A thorough evaluation of neurotrophins is still necessary to determine their time-dependent contributions against injury and their modulatory effects on repair after stroke.

Comprehensive small animal imaging strategies on a clinical 3 T dedicated head MR-scanner; adapted methods and sequence protocols in CNS pathologies.

BACKGROUND: Small animal models of human diseases are an indispensable aspect of pre-clinical research. Being dynamic, most pathologies demand extensive longitudinal monitoring to understand disease mechanisms, drug efficacy and side effects. These considerations often demand the concomitant development of monitoring systems with sufficient temporal and spatial resolution. METHODOLOGY AND RESULTS: This study attempts to configure and optimize a clinical 3 Tesla magnetic resonance scanner to facilitate imaging of small animal central nervous system pathologies. The hardware of the scanner was complemented by a custom-built, 4-channel phased array coil system. Extensive modification of standard sequence protocols was carried out based on tissue relaxometric calculations. Proton density differences between the gray and white matter of the rodent spinal cord along with transverse relaxation due to magnetic susceptibility differences at the cortex and striatum of both rats and mice demonstrated statistically significant differences. The employed parallel imaging reconstruction algorithms had distinct properties dependent on the sequence type and in the presence of the contrast agent. The attempt to morphologically phenotype a normal healthy rat brain in multiple planes delineated a number of anatomical regions, and all the clinically relevant sequels following acute cerebral ischemia could be adequately characterized. Changes in blood-brain-barrier permeability following ischemia-reperfusion were also apparent at a later time. Typical characteristics of intra-cerebral haemorrhage at acute and chronic stages were also visualized up to one month. Two models of rodent spinal cord injury were adequately characterized and closely mimicked the results of histological studies. In the employed rodent animal handling system a mouse model of glioblastoma was also studied with unequivocal results. CONCLUSIONS: The implemented customizations including extensive sequence protocol modifications resulted in images of high diagnostic quality. These results prove that lack of dedicated animal scanners shouldn't discourage conventional small animal imaging studies.