A multi-staged neuropeptide response to traumatic brain injury.

PURPOSE: As the most abundant neuropeptides in Central Nervous System, Substance P and Neuropeptide Y are arguably involved in the response to brain trauma. This study aims to characterize a new concept of multi-staged neuropeptide response to TBI. METHODS: This study assessed Substance P, Neuropeptide Y, S100B, standard inflammatory parameters and ionic disturbance in TBI victims, with and without intracranial lesions, and healthy controls. In the group with intracranial lesions, blood samples were drawn until 6 h after initial trauma, at 48 h and 7 days post-TBI. RESULTS: An early increase in Substance P (mean 613.463 ± 49.055 SE 6 h post-TBI with brain contusions vs. 441.441 ± 22.572 SE pg/dL control group) is evident. Concerning TBI without intraparenchymatous lesions, an increase in substance P is also present (825.60 ± 23.690 SE pg/dL). Following an initial increase and subsequent fall in NPY levels (45.997 ± 4.96 SE 6 h post-TBI vs. 32.395 ± 4.056 SE 48 h post-TBI vs. 19.700 ± 1.462 SE pg/mL control group), a late increase in NPY is obvious (43.268 ± 6.260 SE pg/mL 7 day post-TBI). Post-traumatic hypomagnesemia (0.754 ± 0.015 SE 6 h post-TBI vs. 0.897 ± 0.021 SE mmol/L control group) and a peak in S100B (95.668 ± 14.102 SE 6 h post-TBI vs. 30.187 ± 3.347 SE pg/mL control group) are also present. CONCLUSION: A multi-staged neuropeptide response to TBI is obvious and represents a potential therapeutic strategy for the treatment of intraparenchymal lesions and cerebral edema following TBI.

Subdural false twins: concomitant appearance of subdural haematoma and spontaneous subdural empyema.

A 55-year-old man was taken to the emergency department due to right arm weakness for the past 3 days and fever (39.5°C). There was no impaired consciousness, no history of trauma and meningeal signs were absent on physical examination. Blood analysis and inflammatory markers were not evocative of a systemic infection. A cranial CT scan was requested, revealing hypodense bilateral hemispheric subdural collections, suggestive of chronic subdural haematomas. He was submitted to surgical drainage by burr holes, which confirmed the chronic subdural collection on the left side. Unexpectedly, after dural opening on the right side, a subdural purulent collection was found, which was later confirmed as an empyema due to Escherichia coli infection. A second surgical drainage was performed by craniotomy due to recurrence of the right subdural collection. Spontaneously appearing subdural empyemas due to E. coli are extremely rare and their treatment is not always straightforward. The reported case is an example of an apparently straightforward and frequent pathology that turned out to be a challenging case, requiring a multidisciplinary approach.

World Health Organization Grade III Meningiomas: A Retrospective Study at an Academic Medical Center.

BACKGROUND: Meningiomas are the most common primary brain tumors and are generally considered benign. However, a rare subgroup of meningiomas, classified as World Health Organization (WHO) grade III meningiomas, can show extremely aggressive behavior and high rates of recurrence. Despite ongoing research, data on the clinical outcome of this subgroup of meningiomas are still limited. METHODS: Medical records of patients with WHO grade III meningiomas diagnosed between 2000 and 2018 at the Coimbra University Hospital Center were retrospectively reviewed and several variables of interest and their relation to patients' survival were analyzed. RESULTS: Of the 26 patients included in the final analysis, 23 had anaplastic meningiomas, 2 had papillary meningiomas, and 1 had a rhabdoid meningioma. Median overall survival and median progression-free survival were 2.45 and 1.22 years, respectively. Overall survival at 1, 2 and 5 years was 73%, 57%, and 35%, respectively. Adjuvant radiotherapy correlated with improved survival for subtotally resected meningiomas but not for gross totally resected meningiomas. There was a trend toward improved overall survival with gross total resection versus subtotal resection, but this difference failed to reach statistical significance. CONCLUSIONS: This study provides insight into the clinical outcomes of WHO grade III meningiomas and suggests that adjuvant radiotherapy may not be beneficial for patients who underwent gross total resection. This rare subset of meningiomas still portends a devastating prognosis and the impact of extent of resection and adjuvant therapies in these patients needs further clarification.

Why Does Brain Trauma Research Fail?

Traumatic brain injury (TBI) represents a major health care problem and a significant social and economic issue worldwide. Considering the generalized failure in introducing effective drugs and clinical protocols, there is an urgent need for efficient treatment modalities, able to improve devastating posttraumatic morbidity and mortality. In this work, the status of brain trauma research is analyzed in all its aspects, including basic and translational science and clinical trials. Implicit and explicit challenges to different lines of research are discussed and clinical trial structures and outcomes are scrutinized, along with possible explanations for systematic therapeutic failures and their implications for future development of drug and clinical trials. Despite significant advances in basic and clinical research in recent years, no specific therapeutic protocols for TBI have been shown to be effective. New potential therapeutic targets have been identified, following a better understanding of pathophysiologic mechanisms underlying TBI, although with disappointing results. Several reasons can be pinpointed at different levels, from inaccurate animal models of disease to faulty preclinical and clinical trials, with poor design and subjective outcome measures. Distinct strategies can be delineated to overcome specific shortcomings of research studies. Identifying and contextualizing the failures that have dominated TBI research is mandatory. This review analyzes current approaches and discusses possible strategies for improving outcomes.

Supra and infratentorial ectopic schwannoma mimicking a meningioma.

We report the case of a supra and infratentorial ectopic schwannoma, mimicking a meningioma, that was surgically resected on a 75-year-old man, with a history of progressive visual loss and headaches. MRI was in favour of an occipital, cystic, tentorial-based meningioma extending to the posterior fossa, with signs of intratumoral haemorrhage. This is a unique case because of the rare type of lesion, in a very atypical location, completely unexpected by the preoperative imaging analysis, and to the best of our knowledge it is the oldest patient reported in the literature with this kind of tumour.

A Standardized Classification for Subdural Hematomas- I.

Subdural hematomas are a frequent and highly heterogeneous traumatic disorder, with significant clinical and socioeconomic consequences. In clinical and medicolegal practice, subdural hematomas are classified according to its apparent age, which significantly influences its intrinsic pathogenic behavior, forensic implications, clinical management, and outcome. Although practical, this empirical classification is somewhat arbitrary and scarcely informative, considering the remarkable heterogeneity of this entity. The current research project aims at implementing a comprehensive multifactorial classification of subdural hematomas, allowing a more standardized and coherent assessment and management of this condition. This new method of classification of subdural hematomas takes into account its intrinsic and extrinsic features, using imaging data and histopathological elements, to provide an easily apprehensible and intuitive nomenclature. The proposed classification unifies and organizes all relevant details concerning subdural hematomas, hopefully improving surgical care and forensic systematization.

Screening for brain cancer: why (not): letter.

In an era of emphasis on disease prevention and its early detection, some have raised the possibility of systematic screening programs concerning brain/cranial disease, namely in search of asymptomatic brain tumors. In this work, the authors enumerate major arguments in favor and against this approach by analyzing the existing literature and conclude there is an absence of evidence sustaining this procedure in terms of clinical and economical advantages, with no clear benefit both to the patient and health systems.

Blood-brain barrier and traumatic brain injury.

The blood-brain barrier (BBB) is an anatomical microstructural unit, with several different components playing key roles in normal brain physiological regulation. Formed by tightly connected cerebrovascular endothelial cells, its normal function depends on paracrine interactions between endothelium and closely related glia, with several recent reports stressing the need to consider the entire gliovascular unit in order to explain the underlying cellular and molecular mechanisms. Despite that, with regard to traumatic brain injury (TBI) and significant events in incidence and potential clinical consequences in pediatric and adult ages, little is known about the actual role of BBB disruption in its diverse pathological pathways. This Mini-Review addresses the current literature on possible factors affecting gliovascular units and contributing to posttraumatic BBB dysfunction, including neuroinflammation and disturbed transport mechanisms along with altered permeability and consequent posttraumatic edema. Key mechanisms and its components are described, and promising lines of basic and clinical research are identified, because further knowledge on BBB pathological interference should play a key role in understanding TBI and provide a basis for possible therapeutic targets in the near future, whether through restoration of normal BBB function after injury or delivering drugs in an increased permeability context, preventing secondary damage and improving functional outcome.

Complex sacral fracture.

We reported a case of a patient with suspected cauda equina syndrome secondary to sacral fracture, after sustaining a fall. The difficulty in early diagnosis of complex sacral fractures and the lack of clearly defined guidelines for treatment are highlighted. Thorough clinical examination is mandatory, in order to make an adequate initial assessment and follow symptoms progression and response to treatment. The threshold for performing CT imaging (or MRI, if advised), when suspecting sacral fracture and neurological compromise, should be low. A multidisciplinary approach, with contributions from orthopaedic and/or neurosurgical surgery and physiatry, should be the gold standard of treatment. In this particular case, conservative management and close follow-up led to a significant improvement of problems and a good final outcome, showing that surgical decompression is not the only valid option and that further prospective studies are needed, regarding patient selection and timing of intervention.

Hematoma iatrogênico simulando lesão tumoral intradural lombar / Iatrogenic hematoma mimicking lumbar intradural tumoral lesion

Em um quadro clínico de lombociatalgia, o diagnóstico diferencial engloba uma variedade de possíveis etiologias. Descreve-se um caso de um doente do sexo feminino, com história de lombociatalgia incapacitante relacionada com hematoma intradural, consequência de punção lombar e drenado após laminectomia lombar. São revistas as várias séries descritas na literatura, assim como são discutidos os diferentes fatores de risco, quadros clínicos e estratégias de prevenção e tratamento.

In the presence of lumbar radicular pain, the differential diagnosis includes several possible etiologies. Here is described a case of a female patient with incapacitating low back pain and lumbar radicular pain caused by an intradural hematoma, consequence of lumbar puncture, surgically drained after laminectomy. The several series in the literature describing these cases are revised, and the different risk factors, clinical pictures, prevention and treatment strategies are discussed.

Glutamate and post-traumatic cerebral excitoxicity as possible therapeutic targets ? A literature review / Glutamato e excitotoxicidade cerebral pós-traumática como possíveis alvos terapêuticos ? Revisão da literatura

Cerebral edema and excitoxicity are well known phenomena and are reported in multiple pathological contexts. Despite that, regarding traumatic brain injury, significant events in incidence and potential clinical consequences, little is known about the actual promoting and modulating processes of cerebral damage, namely in relation to glutamate, the main excitatory endogenous neurotransmitter of the central nervous system. Based on current concepts on neuropathology and cerebral regulation, a thorough review is made on the glutamatergic regulation system, its role and mechanisms of action in a secondary response to TBI, namely in cortex and hippocampus, sensible areas to acute and delayed damage. Current and past clinical trials are also mentioned as attempts to modulate these events, with no clinical significance so far. A better knowledge of the glutamatergic deregulation and related excitoxicity should play a key role in the understanding of TBI and provide a basis for possible therapeutic targets in a close future...

O edema cerebral e a excitotoxicidade são fenômenos bem conhecidos e foram descritos em múltiplos contextos patológicos. Apesar disso, em relação ao traumatismo cranioencefálico (TCE), acontecimento significativo em termos de incidência e consequências clínicas, pouco se sabe acerca dos reais processos de promoção e modulação do dano cerebral, nomeadamente em relação ao glutamato, o principal neurotransmissor excitatório endógeno do sistema nervoso central. Baseando-se em conceitos atuais de Neuropatologia e regulação cerebral, é feita uma revisão do sistema de regulação glutamatérgico, o seu papel e mecanismos de ação na resposta secundária ao TCE, nomeadamente no córtex e hipocampo, áreas propensas ao dano imediato e tardio. São referidos os diferentes ensaios clínicos até a data, como tentativas de modulação desses eventos, sem significância clínica até ao momento. Um melhor conhecimento da desregulação glutamatérgica e concomitante excitotoxicidade deverá desempenhar papel crucial na compreensão do TCE e funcionar como ponto de partida para eventuais alvos terapêuticos no futuro...

[Glioblastoma multiforme mimicking limbic encephalitis]. / Glioblastoma multiforme mimetizando encefalite límbica.

Selective and bilateral involvement of the limbic system by gliomas is rarely reported. The authors report the case of a 58 years-male complaining of short-term memory loss in the preceding three weeks. The initial MRI revealed areas of hyperintensity on T2 and FLAIR sequences involving both hippocampus, amygdala, parahippocampus gyrus and the fornix, with contrast enhancement in the right mesial temporal region. Limbic encephalitis diagnosis was assumed and steroid therapy was applied. All other evaluation work-up was negative and follow-up imaging was compatible with tumor. The neuropathologic study of the right temporal lesion revealed glioblastoma multiforme. Glioblastoma can crossover through the commissural white matter to the opposite cerebral hemisphere, most often through the corpus callosum. However, selective and bilateral invasion of the limbic system is rare and when it occurs it may mimic limbic encephalitis.