Measurement of brain simulant strains in head surrogate under impact loading.

Impact-induced traumatic brain injury (TBI) is a major source of disability and mortality. Knowledge of brain strains during impact (accelerative) loading is critical for the overall management of TBI, including the development of injury thresholds, personal protective equipment, and validation of computational models. Despite these needs, the current understanding of brain strains in humans or humanlike surrogates is limited, especially for injury causing loading magnitudes. Toward this end, we measured full-field, in-plane (2D) strains in a brain simulant using the hemispherical head surrogate. The hemispherical head was mounted on the Hybrid-III neck and subjected to impact loading using a linear impactor system. The resulting head kinematics was measured using a triaxial accelerometer and angular rate sensors. Dynamic, 2D strains in a brain simulant were obtained using high-speed imaging and digital image correlation. Concurrent finite element (FE) simulations of the experiment were also performed to gain additional insights. The role of stiff membranes of the head was also studied using experiments. Our results suggest that rotational modes dominate the response of the brain simulant. The wave propagation in the brain simulant as a result of impact has a timescale of ~100 ms. We obtain peak strains of ~20%, ~40%, ~60% for peak rotational accelerations of ~838, ~5170, ~11,860 rad/s2, respectively. Further, peak strains in cortical regions are higher than subcortical regions by up to ~70%. The agreement between the experiments and FE simulations is reasonable in terms of spatiotemporal evolution of strain pattern and peak strain magnitudes. Experiments with the addition of falx and tentorium indicate significant strain concentration (up to 115%) in the brain simulant near the interface of falx or tentorium and brain simulant. Overall, this work provides important insights into the biomechanics of strain in the brain simulant during impact loading.

Cranial Suture Regeneration Mitigates Skull and Neurocognitive Defects in Craniosynostosis.

Craniosynostosis results from premature fusion of the cranial suture(s), which contain mesenchymal stem cells (MSCs) that are crucial for calvarial expansion in coordination with brain growth. Infants with craniosynostosis have skull dysmorphology, increased intracranial pressure, and complications such as neurocognitive impairment that compromise quality of life. Animal models recapitulating these phenotypes are lacking, hampering development of urgently needed innovative therapies. Here, we show that Twist1+/- mice with craniosynostosis have increased intracranial pressure and neurocognitive behavioral abnormalities, recapitulating features of human Saethre-Chotzen syndrome. Using a biodegradable material combined with MSCs, we successfully regenerated a functional cranial suture that corrects skull deformity, normalizes intracranial pressure, and rescues neurocognitive behavior deficits. The regenerated suture creates a niche into which endogenous MSCs migrated, sustaining calvarial bone homeostasis and repair. MSC-based cranial suture regeneration offers a paradigm shift in treatment to reverse skull and neurocognitive abnormalities in this devastating disease.

An Update on Idiopathic Hypertrophic Cranial Pachymeningitis for the Headache Practitioner.

PURPOSE OF REVIEW: We aim to review idiopathic hypertrophic cranial pachymeninigitis (IHCP), describe common head pain patterns and features associated with the disorder, suggest potential classification of head pain syndromes based on the recently published International Classification of Headache Disorders-3, explore pathophysiology found to be associated with cases of IHCP, and indicate common treatment for the disorder. RECENT FINDINGS: It is suggested that a subset of IHCP is an IgG4-related autoimmune disorder. Patients with IHCP were found to have elevated cerebrospinal fluid (CSF) protein and lymphocytic pleocytosis. Corticosteroids are a mainstay of treatment. Other immunosuppressive agents and steroid sparing agents as add-on therapy may have utility in the treatment of cases refractory to corticosteroids alone. Clinical manifestations of IHCP depend upon the location of the inflammatory lesions and compression of the adjacent nervous system structures. Headache and loss of cranial nerve function were the most common presenting features of hypertrophic cranial pachymeninigitis. Several headache diagnoses may result from IHCP. Gadolinium-enhanced MRI is the standard imaging modality for diagnosing. Although the pathophysiology is poorly understood, many cases of hypertrophic pachymeninigitis (HP) are thought to be closely related to inflammatory disorders. Cases of HP previously thought to be idiopathic may have IgG4 pathophysiology. CSF and serological studies are helpful. Treatment involves immunosuppressive agents. Advancement in neuroimaging, assays, tests, and further delineation of inflammatory disorders affecting the nervous system may provide further insight to the etiology of cases of HP previously considered and diagnosed as idiopathic.

iEEG: Dura-lining electrodes.

Intracranial electroencephalography (iEEG) is measured from electrodes placed in or on the brain. These measurements have an excellent signal-to-noise ratio and iEEG signals have often been used to decode brain activity or drive brain-computer interfaces (BCIs). iEEG recordings are typically done for seizure monitoring in epilepsy patients who have these electrodes placed for a clinical purpose: to localize both brain regions that are essential for function and others where seizures start. Brain regions not involved in epilepsy are thought to function normally and provide a unique opportunity to learn about human neurophysiology. Intracranial electrodes measure the aggregate activity of large neuronal populations and recorded signals contain many features. Different features are extracted by analyzing these signals in the time and frequency domain. The time domain may reveal an evoked potential at a particular time after the onset of an event. Decomposition into the frequency domain may show narrowband peaks in the spectrum at specific frequencies or broadband signal changes that span a wide range of frequencies. Broadband power increases are generally observed when a brain region is active while most other features are highly specific to brain regions, inputs, and tasks. Here we describe the spatiotemporal dynamics of several iEEG signals that have often been used to decode brain activity and drive BCIs.

Multiple cerebral arteriovenous malformations associated to rostral hypoplasia of the superior sagittal sinus: a case report.

Multiple cerebral arteriovenous malformations (AVMs) are a rare occurrence usually associated with defined genetic disorders or a family history of cerebrovascular disease. The remaining cases cannot be associated to a genetic pathogenesis and are considered idiopathic. We report an extremely unusual case nor genetic neither idiopathic, but linked to an anatomical intracranial venous variation. The patient presented two independent frontal AVMs associated with rostral hypoplasia of the superior sagittal sinus. This anatomical variation may have induced frontal venous hypertension (VHT) triggering the development of the two AVMs. Throughout this intriguing case, we discuss the role of VHT in AVM development.

Inflammation by activated macrophage-like THP-1 cells increases human dura mater cell adhesion with alteration of integrin α2 ß1 and matrix metalloproteinase.

This study was designed to investigate (i) extracellular matrix to specify adhesive substrates to human dura mater cell (hDMC); (ii) the alteration on adhesion-related molecules in hDMC; and (iii) secreted matrix metalloproteinases (MMPs) linked with extracellular matrix remodeling after exposure to inflammation. The hDMC was cultured from human dura mater tissue, and the studies were performed with hDMC after co-culturing with macrophage like THP-1 cells (Mϕ). The adhesion of co-cultured hDMC through collagen I increased 6.4-fold and through collagen IV increased 5.0-fold compared with the adhesion of naïve cells (p < 0.001). Integrin subtype α2 ß1 expression was increased 6.3-fold (p < 0.001) and α1 expression was decreased 2.0-fold (p < 0.001) in the co-cultured cells compared with the naïve cells. Co-culturing induced significant increases in MMP-1 (13.9-fold, p < 0.01), MMP-3 (7.6-fold, p < 0.01), and VEGF (VEGF: 3.8-fold, p < 0.05) expression and decreases in MMP-9 (0.1-fold, p < 0.01) compared with the sum of naïve hDMC and Mϕ values. Increased hDMC adhesion under inflammatory conditions is caused by an increased cellular affinity for collagen I and IV mediated by increased hDMC levels of integrin subtype α2 ß1 and environmental MMP-1, -3 and decreased MMP-9. Selective integrin subtype α2 ß1 inhibition assay showed 37.8% and 35.7% reduction in adhesion of co-cultured hDMC to collagen I (p < 0.001) and IV (p = 0.057), respectively. The present study provides insight into the pathological conditions related to dura mater adhesion in inflammation. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 9999:1-11, 2019.

Degrees of Diaphragma Sellae Descent during Transsphenoidal Pituitary Adenoma Resection: Predictive Factors and Effect on Outcome.

This study is aimed to classify degrees of diaphragma sellae (DS) descent into sella turcica according to the surgical field block caused by the descent and to construct predictive imaging criteria for the degree of descent, and in addition, to determine whether there is any correlation between the degree of DS descent and the operative outcome (in the form of cerebrospinal fluid leak and/or presence of residual tumor). Totally, 72 patients were enrolled in our study. Their clinical and radiological data as well as the high definition videos of operations were retrospectively reviewed. The degree of DS descent during the operation was classified into five degrees according to surgical field block caused by the descent. We investigated the correlation between these five degrees and the clinical findings, radiological findings as well as the surgical outcomes. We found that the most important determining factors of DS descent degree were the volume and the height of the tumor portion above diaphragma opening. On the other hand, the total tumor volume, the maximum tumor height and the morphological pattern according to Wilson's system (modified from Hardy) had no statistically significant correlation with DS degree of descent. Presence of residual tumor on postoperative magnetic resonance images was significantly correlated with Wilson's classification and with supradiaphragmatic tumor height. On the other hand, cerebrospinal fluid leak showed no statistically significant difference between variable degrees of DS descent. Volumetric data of the tumor portion above the diaphragma opening are more important than morphological data for prediction of surgical field block caused by descended DS. While DS prolapse significantly increases the difficulty of the operative procedure, residual tumor presence is mainly dependent on morphological classification, especially cavernous sinus invasion.

Dural and pial pain-sensitive structures in humans: new inputs from awake craniotomies.

Our knowledge on intracranial pain-sensitive structures in humans comes essentially from observations during neurosurgical procedures performed in awake patients. It is currently accepted that intracranial pain-sensitive structures are limited to the dura mater and its feeding vessels and that small cerebral vessels and pia mater are insensitive to pain, which is inconsistent with some neurosurgical observations during awake craniotomy procedures. We prospectively collected observations of painful events evoked by mechanical stimulation (touching, stretching, pressure, or aspiration) of intracranial structures during awake craniotomies, routinely performed for intraoperative functional mapping to tailor brain tumour resection in the eloquent area. Intraoperatively, data concerning the locations of pain-sensitive structures were drawn by the surgeon on a template and their corresponding referred pain was indicated by the patient by drawing a cross on a diagram representing the head. Ninety-three painful events were observed and collected in 53 different patients (mean age 41.2 years, 25 males) operated on awake craniotomy for left (44 cases) or right (nine cases) supra-tentorial tumour resection in eloquent areas. On average, 1.8 painful events were observed per patient (range 1-5). All the painful events were referred ipsilaterally to the stimulus. In all cases, the evoked pain was sharp, intense and brief, stopped immediately after termination of the causing action, and did not interfere with the continuation of the surgery. In 30 events, pain was induced by stimulation of the dura mater of the skull base (23 events) or of the falx (seven events) and was referred predominantly in the V1 territory and in the temporal region. In 61 cases, pain was elicited by mechanical stimulation of the pia mater or small cerebral vessels of the temporal (19 events), frontal (25 events), parietal (four events) lobes and/or the peri-sylvian region, including the insular lobe (13 events), and referred in the V1 territory. In this observational study, we confirmed that dura of the skull base and dura of the falx cerebri are sensitive to pain and that their mechanical stimulation induced pain mainly referred in the sensory territories of the V1 and V3 divisions of the trigeminal nerve. Unlike earlier studies, we observed that the pia and the small cerebral vessels were also pain-sensitive, as their mechanical stimulation induced pain referred mainly in the V1 territory. These observations suggest that small pial cerebral vessels may also be involved in the pathophysiology of primary and secondary headaches.awy005media15756834882001.

Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis Complicated by Periaortitis and Cranial Hypertrophic Pachymeningitis: A Report of an Autopsy Case.

Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a systemic inflammatory disorder categorized as small-vessel vasculitis. We herein report an elderly Japanese man with AAV (granulomatosis with polyangiitis affecting the eyes, nose, lungs, and kidneys) who also showed periaortitis at the diagnosis and developed cranial hypertrophic pachymeningitis (HP) during steroid maintenance therapy. His consciousness disturbance caused by HP improved after steroid pulse therapy, but he died of aspiration pneumonia. Autopsy findings showed giant cells in the thickened pachymeninges and obsolete inflammatory lesions in the aortic adventitia and renal tubulointerstitium. This is the first case of AAV complicated by periaortitis and cranial HP.

Trombosis de senos venosos durales. Diagnóstico inesperado cerebral / Dural venous sinuses thrombosis; an unexpected diagnosis

No disponible

Combination of dura turning-over and decompressive craniectomy: a new pattern of surgery for cerebral infarction caused by craniocerebral gunshot injury.

BACKGROUND: Craniocerebral gunshot injury refers to a wound caused by a bullet passing through or lodged in brain tissue, resulting in the loss of function of a certain area or other fatal damage to the human brain. Craniocerebral gunshot injury is usually life-threatening and is very common in modern warfare, accounting for the majority of battle casualties. Most of the patients suffer from acute cerebral infarction caused by vascular injury. Lack of early and solid battlefield emergency medical interference adds to the risk of death among the wounded. CASE PRESENTATION: We present a 24-year-old man who was shot with a shotgun from a distance of 15 m in an accidental injury. Forty-seven grapeshots were found on his body surface by physical examination. A computed tomography (CT) scan demonstrated large areas of low-density shadows in his right parietal lobe and right temporal lobe with the midline shifting to the left side 2 days later. Afterwards, the patient was transferred to our emergency medical center at Changzheng Hospital in Shanghai. Cranial computed tomography angiography (CTA) showed a high-density shadow in the initial part of the right middle cerebral artery. The branches after the initial part were obliterated. Prompt medical attention and decompressive craniotomy (DC) surgery contributed to the final recovery from cerebral infarction of this patient. CONCLUSION: Bullets can penetrate or be lodged in the brain, causing intracranial hypertension. The bullets lodged in the brain can result in stenosis and embolism of a cerebral artery, causing acute cerebral infarction. Combining dura turning-over surgery with DC surgery can not only decrease intracranial pressure, which can increase the blood supply for hypertension-induced vessel stenosis, but also help vessels outside the dura mater grow into ischemic areas of the cerebral cortex. However, this new pattern of surgery needs further support from evidence-based medicine.

Protection of cortex by overlying meninges tissue during dynamic indentation of the adolescent brain.

Traumatic brain injury (TBI) has become a recent focus of biomedical research with a growing international effort targeting material characterization of brain tissue and simulations of trauma using computer models of the head and brain to try to elucidate the mechanisms and pathogenesis of TBI. The meninges, a collagenous protective tri-layer, which encloses the entire brain and spinal cord has been largely overlooked in these material characterization studies. This has resulted in a lack of accurate constitutive data for the cranial meninges, particularly under dynamic conditions such as those experienced during head impacts. The work presented here addresses this lack of data by providing for the first time, in situ large deformation material properties of the porcine dura-arachnoid mater composite under dynamic indentation. It is demonstrated that this tissue is substantially stiffer (shear modulus, µ=19.10±8.55kPa) and relaxes at a slower rate (τ1=0.034±0.008s, τ2=0.336±0.077s) than the underlying brain tissue (µ=6.97±2.26kPa, τ1=0.021±0.007s, τ2=0.199±0.036s), reducing the magnitudes of stress by 250% and 65% for strains that arise during indentation-type deformations in adolescent brains. STATEMENT OF SIGNIFICANCE: We present the first mechanical analysis of the protective capacity of the cranial meninges using in situ micro-indentation techniques. Force-relaxation tests are performed on in situ meninges and cortex tissue, under large strain dynamic micro-indentation. A quasi-linear viscoelastic model is used subsequently, providing time-dependent mechanical properties of these neural tissues under loading conditions comparable to what is experienced in TBI. The reported data highlights the large differences in mechanical properties between these two tissues. Finite element simulations of the indentation experiments are also performed to investigate the protective capacity of the meninges. These simulations show that the meninges protect the underlying brain tissue by reducing the overall magnitude of stress by 250% and up to 65% for strains.

Vagus nerve stimulation suppresses acute noxious activation of trigeminocervical neurons in animal models of primary headache.

Vagus nerve stimulation (VNS) has been reported to be effective in the abortive treatment of both migraine and cluster headache. Using validated animal models of acute dural-intracranial (migraine-like) and trigeminal-autonomic (cluster-like) head pain we tested whether VNS suppresses ongoing and nociceptive-evoked firing of trigeminocervical neurons to explain its abortive effects in migraine and cluster headache. Unilateral VNS was applied invasively via hook electrodes placed on the vagus nerve. A single dose of ipsilateral or contralateral VNS, to trigeminal recording and dural-stimulating side, suppressed ongoing spontaneous and noxious dural-evoked trigeminocervical neuronal firing. This effect was dose-dependent, with two doses of ipsilateral VNS prolonging suppression of ongoing spontaneous firing (maximally by ~60%) for up to three hours, and dural-evoked (Aδ-fiber; by ~22%, C-fiber: by ~55%) responses for at least two hours. Statistically, there was no difference between ipsilateral and contralateral groups. Two doses of VNS also suppressed superior salivatory nucleus-evoked trigeminocervical neuronal responses (maximally by ~22%) for 2.5h, to model nociceptive activation of the trigeminal-autonomic pathway. VNS had no effect on normal somatosensory cutaneous facial responses throughout. These studies provide a mechanistic rationale for the observed benefits of VNS in the abortive treatment of migraine and cluster headache. In addition, they further validate these preclinical models as suitable approaches to optimize therapeutic efficacy, and provide an opportunity to hypothesize and dissect the neurobiological mechanisms of VNS in the treatment of primary headaches.

Inhibitory effect of high-frequency greater occipital nerve electrical stimulation on trigeminovascular nociceptive processing in rats.

Electrical stimulation of the greater occipital nerve (GON) has recently shown promise as an effective non-pharmacological prophylactic therapy for drug-resistant chronic primary headaches, but the neurobiological mechanisms underlying its anticephalgic action are not elucidated. Considering that the spinal trigeminal nucleus (STN) is a key segmental structure playing a prominent role in pathophysiology of headaches, in the present study we evaluated the effects of GON electrical stimulation on ongoing and evoked firing of the dura-sensitive STN neurons. The experiments were carried out on urethane/chloralose-anesthetized, paralyzed and artificially ventilated male Wistar rats. Extracellular recordings were made from 11 neurons within the caudal part of the STN that received convergent input from the ipsilateral facial cutaneous receptive fields, dura mater and GON. In each experiment, five various combinations of the GON stimulation frequency (50, 75, 100 Hz) and intensity (1, 3, 6 V) were tested successively in 10 min interval. At all parameter sets, preconditioning GON stimulation (250 ms train of pulses applied before each recording) produced suppression of both the ongoing activity of the STN neurons and their responses to electrical stimulation of the dura mater. The inhibitory effect depended mostly on the GON stimulation intensity, being maximally pronounced when a stimulus of 6 V was applied. Thus, the GON stimulation-induced inhibition of trigeminovascular nociceptive processing at the level of STN has been demonstrated for the first time. The data obtained can contribute to a deeper understanding of neurophysiological mechanisms underlying the therapeutic efficacy of GON stimulation in primary headaches.

Spinal cord injury: is monitoring from the injury site the future?

This paper challenges the current management of acute traumatic spinal cord injury based on our experience with monitoring from the injury site in the neurointensive care unit. We argue that the concept of bony decompression is inadequate. The concept of optimum spinal cord perfusion pressure, which differs between patients, is introduced. Such variability suggests individualized patient treatment. Failing to optimize spinal cord perfusion limits the entry of systemically administered drugs into the injured cord. We conclude that monitoring from the injury site helps optimize management and should be subjected to a trial to determine whether it improves outcome.

Cranial and lumbosacral hypertrophic pachymeningitis associated with systemic lupus erythematosus: A case report.

BACKGROUND: Hypertrophic pachymeningitis (HP) is a chronic disease characterized by inflammatory hypertrophy and fibrosis of dura mater. It can be divided into cranial and spinal forms depending on the location of the lesion. HP involving 2 separate sites simultaneously is quite uncommon. CASE SUMMARY: This study presents a case of a 49-year-old woman with pathologically confirmed cranial and lumbosacral hypertrophic pachymeningitis associated with systemic lupus erythematosus (SLE), which is a rare etiology of HP. She experienced persistent numbness and pain of the left lower limb, followed by headache and seizures. In laboratory tests, levels of erythrocyte sedimentation rate and C-reactive protein were elevated, and antinuclear antibodies and anti-double-strand deoxyribonucleic acid (DNA) antibodies were detected. Magnetic resonance imaging revealed dural thickening with homogenous gadolinium enhancement both at lumbosacral level and over cerebral convexities. Histology suggested chronic inflammation in spinal dura mater with extensive fibrosis, dense lymphoplasmacytic infiltrate, and focal vasculitis. Treatment with corticosteroids and cyclophosphamide was started with significant clinical and radiological improvement. CONCLUSION: HP is etiologically heterogeneous. Despite its rarity, SLE should be considered in the differential diagnosis of HP. Early recognition and therapy may provide an optimal outcome.

The effect of vancomycin powder on human dural fibroblast culture and its implications for dural repair during spine surgery.

OBJECTIVE Surgical site infections (SSIs) are a major source of morbidity after spinal surgery. Several recent studies have described the finding that applying vancomycin powder to the surgical bed may reduce the incidence of SSI. However, applying vancomycin in high concentrations has been shown in vitro to inhibit osteoblast proliferation and to induce cell death. Vancomycin may have a deleterious effect on dural healing after repair of an intentional or unintentional durotomy. This study was therefore undertaken to assess the effect of different concentrations of vancomycin on a human dura mater cell culture. METHODS Human dura intended for disposal after decompressive craniectomy was harvested. Explant primary cultures and subcultures were subsequently performed. Cells were characterized through common staining and immunohistochemistry. A growth curve was performed to assess the effect of different concentrations of vancomycin (40, 400, and 4000 µg/ml) on cell count. The effect of vancomycin on cellular shape, intercellular arrangement, and viability was also evaluated. RESULTS All dural tissue samples successfully developed into fusiform cells, demonstrating pseudopod projections and spindle formation. The cells demonstrated vimentin positivity and also had typical features of fibroblasts. When applied to the cultures, the highest dose of vancomycin induced generalized cell death within 24 hours. The mean (± SD) cell counts for control, 40, 400, and 4000 µg/ml were 38.72 ± 15.93, 36.28 ± 22.87, 19.48 ± 6.53, and 4.07 ± 9.66, respectively (p < 0.0001, ANOVA). Compared with controls, vancomycin-exposed cells histologically demonstrated a smaller cytoplasm and decreased pseudopodia formation resulting in the inhibition of normal spindle intercellular arrangement. CONCLUSIONS When vancomycin powder is applied locally, dural cells are exposed to a concentration several times greater than when delivered systemically. In this in vitro model, vancomycin induced dural cell death, inhibited growth, and altered cellular morphology in a concentration-dependent fashion. Defining a safe vancomycin concentration that is both bactericidal and also does not inhibit normal dural healing is necessary.

A potential mechanism of dural ossification in ossification of ligamentum flavum.

Ossification of the ligamentum flavum (OLF) mostly occurs in the thoracic spine, leading to thoracic spinal stenosis. Surgical treatment is considered as the best option for OLF patients. When the dura mater ossifies, the difficulty of surgery and the risk of complications significantly increase. The cause of dural ossification (DO) is still unknown. Based on the existing research and clinical studies, we propose a potential mechanism of DO in OLF. Firstly, with the progression of OLF, it will compress the dura mater and even the spinal cord. Then, with flexion and extension of spine, relative movement (friction) between the ossified ligamentum flavum and compressed dura mater will lead to local inflammation, subsequently causing dural adhesion. Finally, the adhesion tissue can serve as a pathway for the transportation of osteogenic cytokines (BMP for example) from the ossified ligamentum flavum to the compressed dura mater. Dura will ossify under exposure of these osteogenic cytokines. If this hypothesis is confirmed, it will contribute to the prevention and management of DO. For progressive OLF patients, early surgical treatment before DO should be recommended.