Update: Intentional traumatic brain injury

Intentional traumatic brain injury

Epidemiology

Intentional injury has been associated with certain demographics and socioeconomic groups. Less is known about the relationship of intentional traumatic brain injury (TBI) to injury severity, mortality, and demographic and socioeconomic profile.


A planned secondary analysis of a prospective multicentre cohort study was conducted in 10 emergency departments EDs in Australia and New Zealand, including children aged <18 years with head injury (HI). Epidemiology codes were used to prospectively code the injuries. Demographic and clinical information including the rate of clinically important traumatic brain injury (ciTBI: HI leading to death, neurosurgery, intubation >1 day or admission ≥2 days with abnormal computed tomography [CT]) was descriptively analysed.

Intentional injuries were identified in 372 of 20 137 (1.8%) head-injured children. Injuries were caused by caregivers (103, 27.7%), by peers (97, 26.1%), by siblings (47, 12.6%), by strangers (35, 9.4%), by persons with unknown relation to the patient (21, 5.6%), other intentional injuries (8, 2.2%) or undetermined intent (61, 16.4%). About 75.7% of victims of assault by caregivers were <2 years, whereas in other categories, only 4.9% were <2 years. Overall, 66.9% of victims were male. Rates of CT performance and abnormal CT varied: assault by caregivers 68.9%/47.6%, by peers 18.6%/27.8%, by strangers 37.1%/5.7%. ciTBI rate was 22.3% in assault by caregivers, 3.1% when caused by peers and 0.0% with other perpetrators.

Intentional HI is infrequent in children. The most frequently identified perpetrators are caregivers and peers. Caregiver injuries are particularly severe 1).


A study identified 1,409 (8.0%) intentional TBIs and 16,211 (92.0%) unintentional TBIs. Of the intentional TBIs, 389 (27.6%) was self-inflicted TBI (Si-TBI) and 1,020 (72.4%) was other-inflicted TBI (Oi-TBI). The most common cause of Si-TBI was “jumping from high places” (32.1%), followed by “firearms” (30.6%). About half of Oi-TBI was because of “fight and brawl” (48.3%), followed by “struck by objects” (26.1%). Si-TBI was associated with younger age, female gender, and having more alcohol/drug abuse history. For Oi-TBI, younger age, male gender, having more alcohol/drug abuse history were independently associated.

This research provides the first comprehensive overview of intentional TBI based in Canada.

The comprehensive data set (CDS) of the Ontario trauma registry (OTR) provided the ability to identify who is at risk for intentional TBI. Prevention programs and more targeted rehabilitation services should be designed for this vulnerable population 2).

Outcome

Intentional injury is associated with significant morbidity and mortality.

Caregiver injuries are particularly severe in children 3).

Prospective data were obtained for 2,637 adults sustaining TBIs between January 1994 and September 1998. Descriptive, univariate, and multivariate analyses were conducted to determine the predictive value of intentional TBI on injury severity and mortality.

Gender, minority status, age, substance abuse, and residence in a zipcode with low average income were associated with intentional TBI. Multivariate analysis found minority status and substance abuse to be predictive of intentional injury after adjusting for other demographic variables studied. Intentional TBI was predictive of mortality and anatomic severity of injury to the head. Penetrating intentional TBI was predictive of injury severity with all injury severity markers studied.

Many demographic variables are risk factors for intentional TBI, and such injury is a risk factor for both injury severity and mortality. Future studies are needed to definitively link intentional TBI to disability and functional outcome 4).

References

1) , 3)

Babl FE, Pfeiffer H, Dalziel SR, Oakley E, Anderson V, Borland ML, Phillips N, Kochar A, Dalton S, Cheek JA, Gilhotra Y, Furyk J, Neutze J, Lyttle MD, Bressan S, Donath S, Hearps SJ, Crowe L; Paediatric Research in Emergency Departments International Collaborative (PREDICT). Paediatric intentional head injuries in the emergency department: A multicentre prospective cohort study. Emerg Med Australas. 2018 Nov 26. doi: 10.1111/1742-6723.13202. [Epub ahead of print] PubMed PMID: 30477046.
2)

Kim H, Colantonio A. Intentional traumatic brain injury in Ontario, Canada. J Trauma. 2008 Dec;65(6):1287-92. doi: 10.1097/TA.0b013e31817196f5. PubMed PMID: 19077615.
4)

Wagner AK, Sasser HC, Hammond FM, Wiercisiewski D, Alexander J. Intentional traumatic brain injury: epidemiology, risk factors, and associations with injury severity and mortality. J Trauma. 2000 Sep;49(3):404-10. Erratum in: J Trauma 2000 Nov;49(5):982. PubMed PMID: 11003315.

UpToDate: Agitation

Agitation

Hyperactive delirium (agitation) is an emotional state of excitement or restlessness.

Hyperactive delirium (agitation) is a common complication in patients on intensive care units.

Psychomotor agitation, an extreme form of the above, which can be part of a mental illness or a side effect of anti-psychotic medication.

Assesment

Sedation Agitation Scale.


Postoperative agitation frequently occurs after general anesthesia and may be associated with serious consequences. However, studies in neurosurgical patients have been inadequate.

Huang et al., from the Beijing Tiantan Hospital and the Mongolia People’s Hospital, China. aimed to investigate the incidence and risk factors for early postoperative agitation in patients after craniotomy, specifically focusing on the association between postoperative pneumocephalus and agitation. Adult intensive care unit admitted patients after elective craniotomy under general anesthesia were consecutively enrolled. Patients were assessed using the Sedation Agitation Scale during the first 24 hours after operation. The patients were divided into two groups based on their maximal Sedation-Agitation Scale: the agitation (Sedation-Agitation Scale ≥ 5) and non-agitation groups (Sedation-Agitation Scale ≤ 4). Preoperative baseline data, intraoperative and intensive care unit admission data were recorded and analyzed. Each patient’s computed tomography scan obtained within six hours after operation was retrospectively reviewed. Modified Rankin Scale and hospital length of stay after the surgery were also collected. Of the 400 enrolled patients, agitation occurred in 13.0% (95% confidential interval: 9.7-16.3%). Body mass index, total intravenous anesthesia, intraoperative fluid intake, intraoperative bleeding and transfusionconsciousness after operation, endotracheal intubation kept at intensive care unit admission and mechanical ventilation, hyperglycemia without a history of diabetes, self-reported pain and postoperative bi-frontal pneumocephalus were used to build a multivariable model. Bi-frontal pneumocephalus and delayed extubation after the operation were identified as independent risk factors for postoperative agitation. After adjustment for confounding, postoperative agitation was independently associated with worse neurologic outcome (odd ratio: 5.4, 95% confidential interval: 1.1-28.9, P = 0.048).

The results showed that early postoperative agitation was prevalent among post-craniotomy patients and was associated with adverse outcomes. Improvements in clinical strategies relevant to bi-frontal pneumocephalus should be considered 1).


Sauvigny et al., from the University Medical Centre Hamburg-Eppendorf Germany, performed a retrospective analysis in three hundred thirty-eight patients with aneurysmal subarachnoid hemorrhage resulting in 212 patients which reached at least once a Richmond Sedation Agitation Scale(RASS) of 0 and were eligible for further analysis. Clinical characteristics were analysed towards the occurrence of a hyperactive delirium. Neurological outcome at discharge and follow-up was assessed using the Glasgow Outcome Scale. Seventy-eight of 212 patients (36.8%) developed a hyperactive delirium; the duration ranged from 1 to 11 days. Multivariate regression revealed initial hydrocephalus (odds ratio (OR) 3.21 95% confidence interval (CI) [1.33-7.70]; p = 0.01), microsurgical clipping (OR 3.70 95%CI 1.71-8.01]; p = 0.001), male gender (OR 1.97 95%CI [1.05-3.85]; p = 0.047) and a higher Graeb score (OR 1.11 95%CI [1.00-1.22]; p = 0.043) to be significantly associated with the development of agitation. Medical history of psychiatric disorders, alcohol or nicotine abuse showed no correlation with agitation. Cox regression analysis revealed no significant influence of agitation towards unfavourable outcome at discharge or follow-up.

They provided four independent risk factors for the development of agitation in SAH patients. The study emphasizes the specific entity of agitation in patients with SAH and underscores its relevance in neurological patients 2).

References

1)

Huang HW, Yan LM, Yang YL, He X, Sun XM, Wang YM, Zhang GB, Zhou JX. Bi-frontal pneumocephalus is an independent risk factor for early postoperative agitation in adult patients admitted to intensive care unit after elective craniotomy for brain tumor: A prospective cohort study. PLoS One. 2018 Jul 19;13(7):e0201064. doi: 10.1371/journal.pone.0201064. eCollection 2018. PubMed PMID: 30024979.
2)

Sauvigny T, Mohme M, Grensemann J, Dührsen L, Regelsberger J, Kluge S, Schmidt NO, Westphal M, Czorlich P. Rate and risk factors for a hyperactivity delirium in patients with aneurysmal subarachnoid haemorrhage. Neurosurg Rev. 2018 Jun 9. doi: 10.1007/s10143-018-0990-9. [Epub ahead of print] PubMed PMID: 29948495.

UpToDate: Diffuse axonal injury outcome

Diffuse axonal injury outcome

Diffuse axonal injury, and more generally TBI, often results in physical, cognitive, and behavioral impairments that can be temporary or permanent1) 2) 3) 4) 5) 6) 7) 8) 9) 10).


The outcome of patients after DAI has been linked to the number of lesions identified through imaging. A longitudinal study that analyzed the evolution of traumatic axonal injury using magnetic resonance imaging (MRI) of 58 patients with moderate or severe TBI showed that the greater the number of lesions observed early after trauma, the greater the impairment of functionality after 12 months 11).

A study of 26 DAI patients indicated that the volume and number of lesions identified by MRI performed within 48 h of hospital admission strongly correlated with the level of disability observed at the time of hospital discharge 12).


DAI with hypoxia, as measured by peripheral oxygen saturation, and hypotension with New Injury Severity Score (NISS) value – had a statistically significant association with patient mortality; on the other hand, severity of DAI and length of hospital stay were the only significant predictors for dependence. Therefore, severity of DAI emerged as a risk factor for both mortality and dependence 13).


Clinical evidence of DAI on MRI may only be useful for predicting short-term in-hospital functional outcome. Given no association of DAI and long-term TBI outcomes, providers should be cautious in attributing DAI to future neurologic function, quality of life, and/or survival 14).


Brain atrophy progresses over time, but patients showed better executive function (EF) and verbal episodic memory (EVM) in some of the tests, which could be due to neuroplasticity 15).

References

1)

Gennarelli TA. Cerebral concussion and diffuse brain injuries. 2nd ed In: Cooper PR, editor. , editor. Head Injury. Baltimore: Williams & Wilkins; (1987). p. 108–24.
2)

Gennarelli TA. Cerebral concussion and diffuse brain injuries. 3rd ed In: Cooper PR, editor. , editor. Head Injury. Baltimore: Williams & Wilkins; (1993). p. 137–58.
3)

Lagares A, Ramos A, Alday R, Ballenilla F, Pérez-Nuñez A, Arrese I, et al. Magnetic resonance in moderate and severe head injury: comparative study of CT and MR findings. Characteristics related to the presence and location of diffuse axonal injury in MR. Neurocirugia (Astur) (2006) 17(2):105–18.10.1016/S1130-1473(06)70351-7
4)

Esbjörnsson E, Skoglund T, Sunnerhagen KS. Fatigue, psychosocial adaptation and quality of life one year after traumatic brain injury and suspected traumatic axonal injury; evaluations of patients and relatives: a pilot study. J Rehabil Med (2013) 45:771–7.10.2340/16501977-1170
5)

Chelly H, Chaari A, Daoud E, Dammak H, Medhioub F, Mnif J, et al. Diffuse axonal injury in patients with head injuries: an epidemiologic and prognosis study of 124 cases. J Trauma (2011) 71(4):838–46.10.1097/TA.0b013e3182127baa
6)

Jeong JH, Kim YZ, Cho YW, Kim JS. Negative effect of hypopituitarism following brain trauma in patients with diffuse axonal injury. J Neurosurg (2010) 113(3):532–8.10.3171/2009.10.JNS091152
7)

Ham TE, Sharp DJ. How can investigation of network function inform rehabilitation after traumatic brain injury? Curr Opin Neurol (2012) 25(6):662–9.10.1097/WCO.0b013e328359488f
8)

Sousa RMC. Comparisons among measurement tools in traumatic brain injury outcomes. Rev Esc Enferm USP (2006) 40(2):203–13.10.1590/S0080-62342006000200008
9)

Scholten AC, Haagsma JA, Andriessen TM, Vos PE, Steyerberg EW, van Beeck EF, et al. Health-related quality of life after mild, moderate and severe traumatic brain injury: patterns and predictors of suboptimal functioning during the first year after injury. Injury (2015) 46(4):616–24.10.1016/j.injury.2014.10.064
10)

Liew BS, Johari SA, Nasser AW, Abdullah J. Severe traumatic brain injury: outcome in patients with diffuse axonal injury managed conservatively in hospital Sultanah Aminah, Johor Bahru – an observational study. Med J Malaysia (2009) 64(4):280–8.
11)

Moen KG, Skandsen T, Folvik M, Brezova V, Kvistad KA, Rydland J, et al. A longitudinal MRI study of traumatic axonal injury in patients with moderate and severe traumatic brain injury. J Neurol Neurosurg Psychiatry (2012) 83(12):1193–200.10.1136/jnnp-2012-302644
12)

Schaefer PW, Huisman TA, Sorensen AG, Gonzalez RG, Schwamm LH. Diffusion-weighted MR imaging in closed head injury: high correlation with initial Glasgow Coma Scale score and score on modified Rankin scale at discharge. Radiology (2004) 233(1):58–66.10.1148/radiol.2323031173
13)

Vieira RC, Paiva WS, de Oliveira DV, Teixeira MJ, de Andrade AF, de Sousa RM. Diffuse Axonal Injury: Epidemiology, Outcome and Associated Risk Factors. Front Neurol. 2016 Oct 20;7:178. eCollection 2016. PubMed PMID: 27812349; PubMed Central PMCID: PMC5071911.
14)

Humble SS, Wilson LD, Wang L, Long DA, Smith MA, Siktberg JC, Mirhoseini MF, Bhatia A, Pruthi S, Day MA, Muehlschlegel S, Patel MB. Prognosis of diffuse axonal injury with traumatic brain injury. J Trauma Acute Care Surg. 2018 Jul;85(1):155-159. doi: 10.1097/TA.0000000000001852. PubMed PMID: 29462087; PubMed Central PMCID: PMC6026031.
15)

Stewan Feltrin F, Zaninotto AL, Guirado VMP, Macruz F, Sakuno D, Dalaqua M, Magalhães LGA, Paiva WS, Andrade AF, Otaduy MCG, Leite CC. Longitudinal changes in brain volumetry and cognitive functions after moderate and severe diffuse axonal injury. Brain Inj. 2018 Jul 19:1-10. doi: 10.1080/02699052.2018.1494852. [Epub ahead of print] PubMed PMID: 30024781.

UpToDate: Pediatric intracranial tumor

Pediatric intracranial tumor

Epidemiology

Malignant brain tumors are not uncommon in infants as their occurrence before the age of three represents 20-25% of all malignant brain tumors in childhood.

The location of brain tumors in very young children differs from the posterior fossa predominance of older children. This is especially true in the first 6– 12 months of life, where supratentorial location is signicantly more common.

Approximately 20% of pediatric intracranial tumors arise from the thalamus or brainstem, with an incidence rate of 5% and 15%, respectively.

Medulloblastoma is the most common malignant pediatric intracranial tumor.

Diffuse intrinsic pontine glioma account for 10% to 25% of pediatric intracranial tumor.

Diagnosis

Bächli et al., from the Heidelberg University Hospital, Germany, report a single-institutional collection of pediatric brain tumor cases that underwent a refinement or a change of diagnosis after completion of molecular diagnostics that affected clinical decision-making including the application of molecularly informed targeted therapies. 13 pediatric central nervous system tumors were analyzed by conventional histology, immunohistochemistry, and molecular diagnostics including DNA methylation profiling in 12 cases, DNA sequencing in 8 cases and RNA sequencing in 3 cases. 3 tumors had a refinement of diagnosis upon molecular testing, and 6 tumors underwent a change of diagnosis. Targeted therapy was initiated in 5 cases. An underlying cancer predisposition syndrome was detected in 5 cases. Although this case series, retrospectiveand not population based, has its limitations, insight can be gained regarding precision of diagnosis and clinical management of the patients in selected cases. Accuracy of diagnosis was improved in the cases presented here by the addition of molecular diagnostics, impacting clinical management of affected patients, both in the first-line as well as in the follow-up setting. This additional information may support the clinical decision making in the treatment of challenging pediatric CNS tumors. Prospective testing of the clinical value of molecular diagnostics is currently underway 1).

Treatment

Malignant brain tumors represent a true therapeutic challenge in neurooncology. Before the era of modern imaging and modern neurosurgery these malignant brain tumors were misdiagnosed or could not benefit of the surgical procedures as well as older children because of increased risks in this age group.

The pediatric oncologists are more often confronted with very young children who need a complementary treatment. Before the development of specific approaches for this age group, these children received the same kind of treatment than the older children did, but their survival and quality of life were significantly worse. The reasons of these poor results were probably due in part to the fear of late effects induced by radiation therapy, leading to decrease the necessary doses of irradiation which increased treatment failures without avoiding treatment related complications.

At the end of the 80s, pilot studies were performed using postoperative chemotherapy in young medulloblastoma patients. Van Eys treated 12 selected children with medulloblastoma with MOPP regimen and without irradiation; 8 of them were reported to be long term survivors.

Subsequently, the pediatric oncology cooperative groups studies have designed therapeutic trials for very young children with malignant brain tumors.

Different approaches have been explored: * Prolonged postoperative chemotherapy and delayed irradiation as designed in the POG (Pediatric Oncology Group). * Postoperative chemotherapy without irradiation in the SFOP (Société Française d’Oncologie Pédiatrique) and in the GPO (German Pediatric Oncology) studies. *

The role of high-dose chemotherapy with autologous stem cells transplantation was explored in different ways: High-dose chemotherapy given in all patients as proposed in the Head Start protocol. High-dose chemotherapy given in relapsing patients as salvage treatment in the French strategy. In the earliest trials, the same therapy was applied to all histological types of malignant brain tumors and whatever the initial extension of the disease. This attitude was justified by the complexity of the classification of all brain tumors that has evolved over the past few decades leading to discrepancy between the diagnosis of different pathologists for a same tumor specimen. Furthermore, it has become increasingly obvious that the biology of brain tumors in very young children is different from that seen in older children. However, in the analysis of these trials an effort was made to give the results for each histological groups, according to the WHO classification and after a central review of the tumor specimens. All these collected data have brought to an increased knowledge of infantile malignant brain tumors in terms of diagnosis, prognostic factors and response to chemotherapy. Furthermore a large effort was made to study long term side effects as endocrinopathies, cognitive deficits, cosmetic alterations and finally quality of life in long term survivors. Prospective study of sequelae can bring information on the impact of the different factors as hydrocephalus, location of the tumor, surgical complications, chemotherapy toxicity and irradiation modalities. With these informations it is now possible to design therapeutic trials devoted to each histological types, adapted to pronostic factors and more accurate treatment to decrease long term sequelae 2).

Complications

Case series

1)

Bächli H, Ecker J, van Tilburg C, Sturm D, Selt F, Sahm F, Koelsche C, Grund K, Sutter C, Pietsch T, Witt H, Herold-Mende C, von Deimling A, Jones D, Pfister S, Witt O, Milde T. Molecular Diagnostics in Pediatric Brain Tumors: Impact on Diagnosis and Clinical Decision-Making – A Selected Case Series. Klin Padiatr. 2018 Jul 11. doi: 10.1055/a-0637-9653. [Epub ahead of print] PubMed PMID: 29996150.
2)

Kalifa C, Grill J. The therapy of infantile malignant brain tumors: current status? J Neurooncol. 2005 Dec;75(3):279-85. Review. PubMed PMID: 16195802.

UpToDate: Minocycline

Minocycline

Minocycline attenuates brain swelling and blood brain barrier (BBB) disruption via an iron-chelation mechanism1)

Minocycline has beneficial effects in early brain injury (EBI) following subarachnoid hemorrhage (SAH).

Minocycline treatment significantly reduced germinal matrix hemorrhage (GMH)-induced brain edema, hydrocephalus and brain damage. Minocycline also suppressed upregulation of ferritin after GMH.

Iron plays a role in brain injury following GMH and that minocycline reduces iron overload after germinal matrix hemorrhage (GMH) and iron-induced brain injury 2).


Brain iron overload is involved in brain injury after intracerebral hemorrhage (ICH). There is evidence that systemic administration of minocyclinereduces brain iron level and improves neurological outcome in experimental models of hemorrhagic and ischemic stroke. However, there is evidence in cerebral ischemia that minocycline is not protective in aged female animals. Since most ICH research has used male models, this study was designed to provide an overall view of ICH-induced iron deposits at different time points (1 to 28 days) in aged (18-month old) female Fischer 344 rat ICH model and to investigate the neuroprotective effects of minocycline in those rats. According to our previous studies, we used the following dosing regimen (20 mg/kg, i.p. at 2 and 12 h after ICH onset followed by 10 mg/kg, i.p., twice a day up to 7 days). T2-, T2⁎-weighted and T2⁎ array MRI was performed at 1, 3, 7 and 28 days to measure brain iron content, ventricle volume, lesion volume and brain swelling. Immunohistochemistry was used to examine changes in iron handling proteins, neuronal loss and microglial activation. Behavioral testing was used to assess neurological deficits. In aged female rats, ICH induced long-term perihematomal iron overload with upregulated iron handling proteins, neuroinflammation, brain atrophy, neuronal loss and neurological deficits. Minocycline significantly reduced ICH-induced perihematomal iron overload and iron handling proteins. It further reduced brain swelling, neuroinflammation, neuronal loss, delayed brain atrophy and neurological deficits. These effects may be linked to the role of minocycline as an iron chelator as well as an inhibitor of neuroinflammation 3).

Complications

Consumption of minocycline have been described among the causes associated with idiopathic intracranial hypertension 4).

A 13-year old female patient with a history of acne treated with minocycline who began with severe headache, diplopia and blurred vision. The diagnosis of pseudotumor cerebri was made, indicating the immediate antibiotic suspension and the beginning of the treatment with acetazolamide. Although the pathogenesis of pseudotumor cerebri is not fully known, an association with minocycline has been observed. This antibiotic is often used by health professionals for the management of acne, so it is important to consider its complications before being prescribed 5).

Subarachnoid hemorrhage

The molecular mechanisms underlying these effects have not been clearly identified.

SAH was induced by the filament perforation model of SAH in male Sprague Dawley rats. Minocycline or vehicle was given via an intraperitoneal injection 1 h after SAH induction. Minocycline treatment markedly attenuated brain edema secondary to blood-brain barrier (BBB) dysfunction by inhibiting NLRP3 inflammasome activation, which controls the maturation and release of pro-inflammatory cytokines, especially interleukin-1β (IL-1β). Minocycline treatment also markedly reduced the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive cells. To further identify the potential mechanisms, we demonstrated that minocycline increased Bcl2 expression and reduced the protein expression of P53, Bax, and cleaved caspase-3. In addition, minocycline reduced the cortical levels of reactive oxygen species (ROS), which are closely related to both NLRP3 inflammasome and P53 expression. Minocycline protects against NLRP3 inflammasome-induced inflammation and P53-associated apoptosis in early brain injury following SAH. Minocycline’s anti-inflammatory and anti-apoptotic effect may involve the reduction of ROS. Minocycline treatment may exhibit important clinical potentials in the management of SAH 6).

Case series

To predict the feasibility of conducting clinical trials of acute SCI within Canada, Thibault-Halman et al., have applied the inclusion/exclusion criteria of six previously conducted SCI trials to the RHSCIR dataset and generated estimates of how many Canadian individuals would theoretically have been eligible for enrollment in these studies. Data for SCI cases were prospectively collected for RHSCIR at 18 acute and 13 rehabilitation sites across Canada. RHSCIR cases enrolled between 2009-2013 who met the following key criteria were included: non-penetrating traumatic SCI; received acute care at a RHSCIR site; age >18- <75 years, and had complete admission single neurological level of injury data. Inclusion and exclusion criteria for the Minocycline in Acute Spinal Cord injury (Minocycline), Riluzole, Surgical Timing in Acute Spinal Cord Injury Study (STASCIS), Cethrin, Nogo antibody study (NOGO) and Sygen studies were applied retrospectively to this dataset. The numbers of patients eligible for each clinical trial were determined. 2166 of the initial 2714 cases (79.8%) met the key criteria and were included in the dataset. Projected annual numbers of eligible patients for each trial was: Minocycline 117 cases; Riluzole 62 cases; STASCIS 109 cases; Cethrin 101 cases; NOGO 82 cases; and Sygen 70 cases. An additional 8.0% of the sample had a major head injury (GCS≤ 12) and would have been excluded from the trials. RHSCIR provides a comprehensive national dataset which may serve as a useful tool in the planning of multicentre clinical SCI trials 7).

References

1)

Zhao F, Xi G, Liu W, Keep RF, Hua Y. Minocycline Attenuates Iron-Induced Brain Injury. Acta Neurochir Suppl. 2016;121:361-5. doi: 10.1007/978-3-319-18497-5_62. PubMed PMID: 26463975.

2)

Guo J, Chen Q, Tang J, Zhang J, Tao Y, Li L, Zhu G, Feng H, Chen Z. Minocycline-induced attenuation of iron overload and brain injury after experimental germinal matrix hemorrhage. Brain Res. 2015 Jan 12;1594:115-24. doi: 10.1016/j.brainres.2014.10.046. Epub 2014 Oct 31. PubMed PMID: 25451129.

3)

Dai S, Hua Y, Keep RF, Novakovic N, Fei Z, Xi G. Minocycline attenuates brain injury and iron overload after intracerebral hemorrhage in aged female rats. Neurobiol Dis. 2018 Jun 4. pii: S0969-9961(18)30173-6. doi: 10.1016/j.nbd.2018.06.001. [Epub ahead of print] Review. PubMed PMID: 29879529.

4) , 5)

González Gili LO, Buffone IR, Carrara LE, Coto MB, Fortunatti EA, Dejtera M, García Elliot MF, Giacone A, Luncio AC, Masnicoff SD, Oviedo Crosta MB, Parroua M, Romano M. [Pseudotumor cerebri secondary to consumption of minocycline in a pediatric patient]. Arch Argent Pediatr. 2016 Apr 1;114(1):e78-e83. doi: 10.5546/aap.2016.e78. Epub 2016 Apr 1. Spanish. PubMed PMID: 27079408.

6)

Li J, Chen J, Mo H, Chen J, Qian C, Yan F, Gu C, Hu Q, Wang L, Chen G. Minocycline Protects Against NLRP3 Inflammasome-Induced Inflammation and P53-Associated Apoptosis in Early Brain Injury After Subarachnoid Hemorrhage. Mol Neurobiol. 2015 Jul 5. [Epub ahead of print] PubMed PMID: 26143258.

7)

Thibault-Halman G, Rivers CS, Bailey C, Tsai E, Drew B, Noonan V, Fehlings M, Dvorak MF, Kuerban D, Kwon BK, Christie S. Predicting recruitment feasibility for acute spinal cord injury clinical trials in Canada using national registry data. J Neurotrauma. 2016 Sep 14. [Epub ahead of print] PubMed PMID: 27627704.

UpToDate: HeadSense medical

HeadSense medical

HeadSense Medical develops inexpensive, easy-to-use devices for patient monitoring and diagnosis of cerebral dysfunction. The HS-1000 is the first product of the company.

The author and the developer of the device, as well as the co-founder and scientific director of the company is Surik Papyan, who is originally from Armenia and currently resides in Israel.


What are the advantages of the HS-1000 over the existing invasive and noninvasive ICP monitoring methods?

Figuratively speaking, the HS-1000 “listens” to our brains.

“The brain, just like the rest of the body, makes a noise when it works. This noise is at “low frequencies,” so we do not hear it. The sound of our circulatory system can be compared with the sounds of running water. The blood makes a different noise when it passes through too narrow or too wide vessels,” Surik Papyan explained.

We can “hear” these “sounds” only when we put a microphone in the ear canal, because of the fact that the outer ear canal, being hermetically sealed, becomes a unique resonator, something like an “organ pipe,” according to Alexander Khachunts, who is the head of the Laboratory of Psychophysiology of the National Academy of Sciences of Armenia and also took part in this project.

Just as a skilled mechanic can detect faults in a vehicle by listening to the sound of the engine, the HS-1000 can identify problems in the brain by listening to its sounds. The mathematical algorithms implemented in the device allow to dynamically measure and display the value of intracranial pressure.

The HS-1000 is equipped with a microphone, which is placed in the ear and records the mixed acoustic signal, which is formed by hemodynamic and liquorodynamic processes in the brain. It also records the air flow in the upper airways.

The acoustic signal is transmitted from the microphone to a tablet, PC or a mobile device with a special application installed. This application calculates the level of intracranial pressure and the physiological parameters needed to assess the patient’s condition. Then the results are displayed.

see more https://med.news.am/eng/news/9852/new-noninvasive-method-of-intracranial-pressure-monitoring-hs-1000-listens-to-the-brain.html


In a study a new method of Noninvasive intracranial pressure monitoring performed using algorithms to determine ICP based on acoustic properties of the brain was applied in patients undergoing invasive intracranial pressure monitoring, and the results were analyzed.

In patients with traumatic brain injury and subarachnoid hemorrhage who were undergoing treatment in a intensive neurocritical care unit, Ganslandt et al., from the Department of Neurosurgery, Klinikum Stuttgart; and Department of Neurosurgery, University of ErlangenGermanyrecorded ICP using the gold standard method of invasive external ventricular drainage or intraparenchymal monitoring. In addition, they simultaneously measured the ICP noninvasively with a device (the HS-1000) that uses advanced signal analysis algorithms for acoustic signals propagating through the cranium. To assess the accuracy of the NI-ICP method, data obtained using both I-ICP and NI-ICP monitoring methods were analyzed with MATLAB to determine the statistical significance of the differences between the ICP measurements obtained using NI-ICP and I-ICP monitoring.

Data were collected in 14 patients, yielding 2543 data points of continuous parallel ICP values in recordings obtained from I-ICP and NI-ICP. Each of the 2 methods yielded the same number of data points. For measurements at the ≥ 17-mm Hg cutoff, which was arbitrarily chosen for this preliminary analysis, the sensitivity and specificity for the NI-ICP monitoring were found to be 0.7541 and 0.8887, respectively. Linear regression analysis indicated that there was a strong positive relationship between the measurements. Differential pressure between NI-ICP and I-ICP was within ± 3 mm Hg in 63% of data-paired readings and within ± 5 mm Hg in 85% of data-paired readings. The receiver operating characteristic-area under the curve analysis revealed that the area under the curve was 0.895, corresponding to the overall performance of NI-ICP monitoring in comparison with I-ICP monitoring.

This study provides the first clinical data on the accuracy of the HS-1000 NI-ICP monitor, which uses advanced signal analysis algorithms to evaluate properties of acoustic signals traveling through the brain in patients undergoing I-ICP monitoring. The findings of this study highlight the capability of this NI-ICP device to accurately measure ICP noninvasively. Further studies should focus on clinical validation for elevated ICP values1).

1)

Ganslandt O, Mourtzoukos S, Stadlbauer A, Sommer B, Rammensee R. Evaluation of a novel noninvasive ICP monitoring device in patients undergoing invasive ICP monitoring: preliminary results. J Neurosurg. 2018 Jun;128(6):1653-1660. doi: 10.3171/2016.11.JNS152268. Epub 2017 Aug 8. PubMed PMID: 28784032.

UpToDate: Cranioplasty timing

Cranioplasty timing

There is an increasing body of evidence in the recent literature, which demonstrates that cranioplasty may also accelerate and improve neurological recovery. Although the exact pathophysiological mechanisms for this improvement remain essentially unknown, there are a rapidly growing number of neurosurgeons adopting this concept.

Cranioplasty performed between 15 and 30 days after initial craniectomy may minimize infectionseizure, and bone flap resorption, whereas waiting > 90 days may minimize hydrocephalus but may increase the risk of seizure 1).


Communicating hydrocephalus is an almost universal finding in patients after hemicraniectomy. Delayed time to cranioplasty is linked with the development of persistent hydrocephalus, necessitating permanent CSF diversion in some patients.

Waziri et al., propose that early cranioplasty, when possible, may restore normal intracranial pressure dynamics and prevent the need for permanent CSF diversion in patients after hemicraniectomy 2).

Factors

One modifiable factor that may alter the risk of cranioplasty is the timing of cranioplasty after craniectomy. Case series suggest that early cranioplasty is associated with higher rates of infection while delaying cranioplasty may be associated with higher rates of bone resorption.

When considering ideal timing for cranioplasty, predominant issues include residual brain edema, brain retraction into the cranial vault, risk of infection, and development of delayed post-traumatic hydrocephalus.


Waiting to perform cranioplasty is important to prevent the development of devitalized autograft or allograft infections.

It is generally accepted to wait 3 to 6 months before reconstructive surgery. If there is an infected area, this waiting period can be as long as one year.

Cranioplasty is performed after craniectomy when intracranial pressure is under control for functional and aesthetic restorations and for protection, but it may also lead to some neurological improvement after the bone flap placement 3) 4) 5).

Timing of cranioplasty after decompressive craniectomy for trauma

The optimal timing of cranioplasty after decompressive craniectomy for trauma is unknown.

After decompressive craniectomy for trauma, early (<12 weeks) cranioplasty does not alter the incidence of complication rates. In patients <18 years of age, early (<12 weeks) cranioplasty increases the risk of bone resorption. Delaying cranioplasty (≥12 weeks) results in longer operative times and may increase costs 6).

Timing of cranioplasty after decompressive craniectomy for malignant middle cerebral artery infarction

Patients with malignant middle cerebral artery infarction frequently develop hydrocephalus after decompressive hemicraniectomy. Hydrocephalus itself and known shunt related complications after ventriculoperitoneal shunt implantation may negatively impact patients outcome.

A later time point of cranioplasty might lead to a lower incidence of required shunting procedures in general 7).

References

1)

Morton RP, Abecassis IJ, Hanson JF, Barber JK, Chen M, Kelly CM, Nerva JD, Emerson SN, Ene CI, Levitt MR, Chowdhary MM, Ko AL, Chesnut RM. Timing of cranioplasty: a 10.75-year single-center analysis of 754 patients. J Neurosurg. 2018 Jun;128(6):1648-1652. doi: 10.3171/2016.11.JNS161917. Epub 2017 Aug 11. PubMed PMID: 28799868.

2)

Waziri A, Fusco D, Mayer SA, McKhann GM 2nd, Connolly ES Jr. Postoperative hydrocephalus in patients undergoing decompressive hemicraniectomy for ischemic or hemorrhagic stroke. Neurosurgery. 2007 Sep;61(3):489-93; discussion 493-4. PubMed PMID: 17881960.

3)

Honeybul S, Janzen C, Kruger K, Ho KM. The impact of cranioplasty on neurological function. Br J Neurosurg. 2013;27:636–641. doi: 10.3109/02688697.2013.817532.

4)

Jelcic N, De Pellegrin S, Cecchin D, Della Puppa A, Cagnin A. Cognitive improvement after cranioplasty: a possible volume transmission-related effect. Acta Neurochir (Wien) 2013;155:1597–1599. doi: 10.1007/s00701-012-1519-6.

5)

Di Stefano C, Sturiale C, Trentini P, Bonora R, Rossi D, Cervigni G, et al. Unexpected neuropsychological improvement after cranioplasty: a case series study. Br J Neurosurg. 2012;26:827–831. doi: 10.3109/02688697.2012.692838.

6)

Piedra MP, Nemecek AN, Ragel BT. Timing of cranioplasty after decompressive craniectomy for trauma. Surg Neurol Int. 2014 Feb 25;5:25. doi: 10.4103/2152-7806.127762. PubMed PMID: 24778913; PubMed Central PMCID: PMC3994696.

7)

Finger T, Prinz V, Schreck E, Pinczolits A, Bayerl S, Liman T, Woitzik J, Vajkoczy P. Impact of timing of cranioplasty on hydrocephalus after decompressive hemicraniectomy in malignant middle cerebral artery infarction. Clin Neurol Neurosurg. 2016 Dec 9;153:27-34. doi: 10.1016/j.clineuro.2016.12.001. [Epub ahead of print] PubMed PMID: 28012353.

Update: Pupil Reactivity Score

Pupil Reactivity Score

The GCS Pupils Score (GCS-P) was described by Paul Brennan, Gordon Murray and Graham Teasdale in 2018 as a strategy to combine the two key indicators of the severity of traumatic brain injury into a single simple index.

How do I calculate the GCS-P?

The GCS-P is calculated by subtracting the Pupil Reactivity Score (PRS) from the Glasgow Coma Scale (GCS) total score:

GCS-P = GCS – PRS

The Pupil Reactivity Score is calculated as follows.

see more at http://www.glasgowcomascale.org/what-is-gcs-p/


Information about early GCS scores, pupil responses, late outcomes on the Glasgow Outcome Scale, and mortality were obtained at the individual patient level by reviewing data from the CRASH (Corticosteroid Randomisation After Significant Head Injury; n = 9,045) study and the IMPACT(International Mission for Prognosis and Clinical Trials in TBI; n = 6855) database. These data were combined into a pooled data set for the main analysis.

Methods of combining the Glasgow Coma Scale and pupil reaction data varied in complexity from using a simple arithmetic score (GCS score [range 3-15] minus the number of nonreacting pupils [0, 1, or 2]), which Brennan et al., called the GCS Pupils score (GCS-P; range 1-15), to treating each factor as a separate categorical variable. The content of information about patient outcome in each of these models was evaluated using Nagelkerke R2.

Separately, the GCS score and pupil response were each related to outcome. Adding information about the pupil response to the GCS score increased the information yield. The performance of the simple GCS-P was similar to the performance of more complex methods of evaluating traumatic brain damage. The relationship between decreases in the GCS-P and deteriorating outcome was seen across the complete range of possible scores. The additional 2 lowest points offered by the GCS-Pupils scale (GCS-P 1 and 2) extended the information about injury severity from a mortality rate of 51% and an unfavorable outcome rate of 70% at GCS score 3 to a mortality rate of 74% and an unfavorable outcome rate of 90% at GCS-P 1. The paradoxical finding that GCS score 4 was associated with a worse outcome than GCS score 3 was not seen when using the GCS-P.

A simple arithmetic combination of the GCS score and pupillary response, the GCS-P, extends the information provided about patient outcome to an extent comparable to that obtained using more complex methods. The greater range of injury severities that are identified and the smoothness of the stepwise pattern of outcomes across the range of scores may be useful in evaluating individual patients and identifying patient subgroups. The GCS-P may be a useful platform onto which information about other key prognostic features can be added in a simple format likely to be useful in clinical practice 1).

1)

Brennan PM, Murray GD, Teasdale GM. Simplifying the use of prognostic information in traumatic brain injury. Part 1: The GCS-Pupils score: an extended index of clinical severity. J Neurosurg. 2018 Jun;128(6):1612-1620. doi: 10.3171/2017.12.JNS172780. Epub 2018 Apr 10. PubMed PMID: 29631516.

Update: Antiplatelet reversal

Antiplatelet reversal

Antiplatelet therapy is common and complicates the operative management of acute intracranial hemorrhage. Little data exist to guide antiplatelet reversal strategies.

The use of antithrombotic agents, including anticoagulants, antiplatelet agents, and thrombolytics has increased and is expected to continue to rise. Although antithrombotic-associated intracranial hemorrhage can be devastating, rapid reversal of coagulopathy may help limit hematoma expansion and improve outcomes.

Data assessing the relationship between outcome and prehospital antiplatelet agents in the setting of ICH is conflicting in both the trauma and the stroke literature. Only one retrospective review specifically addressed outcomes after attempted reversal with platelet transfusion. Further study is needed to determine whether platelet transfusion ameliorates hematoma enlargement and/or improves outcome in the setting of acute ICH 1).

Raimondi et al., recommend discontinuation of the antiplatelet, as well as administration of platelet transfusions and desmopressin only in the setting of life-threatening bleeding 2).


An online survey detailing antiplatelet reversal strategies in patients presenting with acute operative intracranial hemorrhage (subdural hematoma(SDH), epidural hematoma (EDH), and intracerebral hemorrhage (ICH) was distributed to board certified neurosurgeons in the North America.

Of the 2,782 functional email addresses, there were 493 (17.7%) responses to question #1 and 429 (15.4%) completed surveys. Most respondents chose to perform no additional laboratory testing prior to surgical intervention, regardless of hemorrhage type. The most common antiplatelet reversal strategy in the presence of aspirin was platelet transfusion (SDH and ICH) or no intervention (EDH). The most common antiplatelet reversal strategy in the presence of an Adenosine diphosphate receptor inhibitor or DAPT was platelet transfusion or platelet transfusion with DDAVP administration. There was a statistically significant difference in management strategy depending on the antiplatelet therapy (p < 0.001).

When patients on antiplatelet medication present with operative intracranial hemorrhage, the majority of neurosurgeons do not perform qualitative platelet function testing. Antiplatelet reversal strategies are significantly influenced by the antiplatelet therapy with more aggressive reversal strategies employed in the presence of ADP antagonist3).

References

1)

Campbell PG, Sen A, Yadla S, Jabbour P, Jallo J. Emergency reversal of antiplatelet agents in patients presenting with an intracranial hemorrhage: a clinical review. World Neurosurg. 2010 Aug-Sep;74(2-3):279-85. doi: 10.1016/j.wneu.2010.05.030. Review. PubMed PMID: 21492561.
2)

Raimondi P, Hylek EM, Aronis KN. Reversal Agents for Oral Antiplatelet and Anticoagulant Treatment During Bleeding Events: Current Strategies. Curr Pharm Des. 2017;23(9):1406-1423. doi: 10.2174/1381612822666161205110843. Review. PubMed PMID: 27917717.
3)

Foreman PM, Ilyas A, Mooney J, Schmalz PGR, Walters BC, Griessenauer CJ. Antiplatelet Medication Reversal Strategies in Operative Intracranial Hemorrhage: A Survey of Practicing Neurosurgeons. World Neurosurg. 2018 May 18. pii: S1878-8750(18)31017-9. doi: 10.1016/j.wneu.2018.05.064. [Epub ahead of print] PubMed PMID: 29783009.
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