Mild traumatic brain injury

Mild traumatic brain injury

Latest mild traumatic brain injury- related PubMed Articles

Definition

Mild TBI, often called “concussion,” is defined by a GCS of 14 to 15 and accounts for over 80% of TBI 1).

see Mild traumatic brain injury definition.

Epidemiology

Mild traumatic brain injury epidemiology.

Classification

see Mild Traumatic Brain Injury Classification.

Biomarkers

see Mild Traumatic Brain Injury Biomarkers.

S100B in mild traumatic brain injury

Neurometabolic cascade

Recommendation: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3211100/

The initial ionic flux and glutamate release result in significant energy demands and a period of metabolic crisis for the injured brain. These physiological perturbations can now be linked to clinical characteristics of concussion, including migrainous symptoms, vulnerability to repeat injury, and cognitive impairment. Furthermore, advanced neuroimaging now allows a research window to monitor postconcussion pathophysiology in humans noninvasively. There is also increasing concern about the risk for chronic or even progressive neurobehavioral impairment after concussion/mild traumatic brain injury. Critical studies are underway to better link the acute pathobiology of concussion with potential mechanisms of chronic cell death, dysfunction, and neurodegeneration 2).

Glutamate release and ionic disequilibrium

As a result of mechanical trauma, neuronal cell membranes and axons undergo disruptive stretching, leading to temporary ionic disequilibrium 3).

As a result, levels of extracellular potassium increase drastically, and indiscriminate glutamate release occurs 4).

Glutamate release activates N-methyl-D-aspartate receptors, which leads to accumulation of intracellular calcium 5) 6) 7) , causing mitochondrial respiration dysfunction, protease activation, and often initiating apoptosis 8) 9). Elevated glutamate levels were also found to be significantly correlated with derangements in lactate, potassium, brain tissue pH, and brain tissue CO2 levels in human studies 10). Additionally, sodium channel upregulation, fueled by ATPase proteins depending on glucose for energy, is observed following axonal stretch injuries 11).

Energy crisis and mitochondrial dysfunction

In combination, the cellular response to the above-mentioned ionic shifts and the downstream effects of the neurotransmitter release lead to an acute energy crisis. This occurs when, to restore ionic equilibrium, adenosine-triphosphate (ATP) -dependent sodium-potassium ion transporter pump activity increases, which augments local cerebral glucose demand 12).

Further metabolic demand is incurred by ATP-dependent sodium channel upregulation. This occurs in the face of mitochondrial dysfunction, leading cells to primarily utilize glycolytic pathways instead of aerobic metabolism for energy, and causing extracellular lactate accumulation as a byproduct 13). This acidosis, caused by hyperglycolysis, has been shown to worsen membrane permeability, ionic disequilibrium, and cerebral edema 14).

Some evidence shows that the lactate produced by this process may eventually be utilized as a source of energy by the neurons once mitochondrial oxidative respiration normalizes; in fact, one study showed that in moderate to severe TBI the incidence of abnormally high levels of lactate uptake were seen in 28% of subjects 15). The same study showed that patients exhibiting a higher rate of brain lactate uptake relative to arterial lactate levels tended to have more favorable outcomes compared to others with lower relative lactate uptake.

Alterations in cerebral blood flow

Some studies have shown that cerebral blood flow decreases immediately following the insult, and the amount of time it remains lowered seems to depend on the severity of the injury 16) 17).

Other studies, however, show no significant differences in CBF following mild TBI in subjects over 30 years of age 18). In pediatric studies, CBF has been seen to increase during the first day following mild TBI, followed by decreased CBF for many days after 19) 20). Data comparing cerebral blood flow in pediatric TBI patients has shown impaired autoregulation in 42% of moderate and severe and 17% of mild injuries 21).

Histopathologic changes

The underlying histopathologic changes that occur are relatively unknown. In order to improve understanding of acute injury mechanisms, appropriately designed pre-clinical models must be utilized.

The clinical relevance of compression wave injury models revolves around the ability to produce consistent histopathologic deficits. Mild traumatic brain injuries activate similar neuroinflammatory cascades, cell death markers and increases in amyloid precursor protein in both humans and rodents. Humans, however, infrequently succumb to mild traumatic brain injuries and, therefore, the intensity and magnitude of impacts must be inferred. Understanding compression wave properties and mechanical loading could help link the histopathologic deficits seen in rodents to what might be happening in human brains following concussions 22).

Clinical Features

see Mild traumatic brain injury clinical features.

Diagnosis

see Mild traumatic brain injury diagnosis.

Guidelines

Mild traumatic brain injury guideline

Treatment

Mild traumatic brain injury treatment.

Complications

see Mild traumatic brain injury complications.

Case series

Mild traumatic brain injury case series.

Case reports

Mild traumatic brain injury case reports.

1)

Ginsburg J, Huff JS. Closed Head Trauma. 2023 Feb 7. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 32491784.
2)

Giza CC, Hovda DA. The new neurometabolic cascade of concussion. Neurosurgery. 2014 Oct;75 Suppl 4:S24-33. doi: 10.1227/NEU.0000000000000505. PubMed PMID: 25232881.
3)

Farkas O, Lifshitz J, Povlishock JT. Mechanoporation induced by diffuse traumatic brain injury: an irreversible or reversible response to injury? J Neurosci. 2006 Mar 22;26(12):3130–3140.
4)

Katayama Y, Becker DP, Tamura T, Hovda DA. Massive increases in extracellular potassium and the indiscriminate release of glutamate following concussive brain injury. J Neurosurg. 1990 Dec;73(6):889–900.
5)

Osteen CL, Giza CC, Hovda DA. Injury-induced alterations in N-methyl-D-aspartate receptor subunit composition contribute to prolonged 45 calcium accumulation following lateral fluid percussion. Neuroscience. 2004;128(2):305–322.
6)

Osteen CL, Moore AH, Prins ML, Hovda DA. Age-dependency of 45calcium accumulation following lateral fluid percussion: acute and delayed patterns. J Neurotrauma. 2001 Feb;18(2):141–162.
7)

Fineman I, Hovda DA, Smith M, Yoshino A, Becker DP. Concussive brain injury is associated with a prolonged accumulation of calcium: a 45Ca autoradiographic study. Brain Research. 1993;624(1–2):94–102.
8)

Raghupathi R. Cell death mechanisms following traumatic brain injury. Brain Pathol. 2004 Apr;14(2):215–222.
9)

Sullivan PG, Rabchevsky AG, Waldmeier PC, Springer JE. Mitochondrial permeability transition in CNS trauma: cause or effect of neuronal cell death? J Neurosci Res. 2005 Jan 1–15;79(1–2):231–239.
10)

Reinert M, Hoelper B, Doppenberg E, Zauner A, Bullock R. Substrate delivery and ionic balance disturbance after severe human head injury. Acta Neurochir Suppl. 2000;76:439–444.
11)

Yuen TJ, Browne KD, Iwata A, Smith DH. Sodium channelopathy induced by mild axonal trauma worsens outcome after a repeat injury. J Neurosci Res. 2009 Dec;87(16):3620–3625.
12)

Yoshino A, Hovda DA, Kawamata T, Katayama Y, Becker DP. Dynamic changes in local cerebral glucose utilization following cerebral concussion in rats: evidence of a hyper- and subsequent hypometabolic state. Brain Research. 1991;561(1):106–119.
13)

Kawamata T, Katayama Y, Hovda DA, Yoshino A, Becker DP. Lactate accumulation following concussive brain injury: the role of ionic fluxes induced by excitatory amino acids. Brain Research. 1995;674(2):196–204.
14)

Kalimo H, Rehncrona S, Soderfeldt B. The role of lactic acidosis in the ischemic nerve cell injury. Acta Neuropathol Suppl (Berl) 1981;7:20–22.
15)

Glenn TC, Kelly DF, Boscardin WJ, et al. Energy dysfunction as a predictor of outcome after moderate or severe head injury: indices of oxygen, glucose, and lactate metabolism. J Cereb Blood Flow Metab. 2003 Oct;23(10):1239–1250.
16)

Golding EM, Steenberg ML, Contant CF, Jr, Krishnappa I, Robertson CS, Bryan RM., Jr Cerebrovascular reactivity to CO(2) and hypotension after mild cortical impact injury. Am J Physiol. 1999 Oct;277(4 Pt 2):H1457–1466.
17)

Grindel SH. Epidemiology and pathophysiology of minor traumatic brain injury. Curr Sports Med Rep. 2003 Feb;2(1):18–23.
18)

Chan KH, Miller JD, Dearden NM. Intracranial blood flow velocity after head injury: relationship to severity of injury, time, neurological status and outcome. J Neurol Neurosurg Psychiatry. 1992 Sep;55(9):787–791.
19)

Mandera M, Larysz D, Wojtacha M. Changes in cerebral hemodynamics assessed by transcranial Doppler ultrasonography in children after head injury. Childs Nerv Syst. 2002 Apr;18(3–4):124–128.
20)

Becelewski J, Pierzchala K. Cerebrovascular reactivity in patients with mild head injury. Neurol Neurochir Pol. 2003 Mar-Apr;37(2):339–350.
21)

Vavilala MS, Lee LA, Boddu K, et al. Cerebral autoregulation in pediatric traumatic brain injury. Pediatr Crit Care Med. 2004;5(3):257–263.
22)

Lucke-Wold BP, Phillips M, Turner RC, Logsdon AF, Smith KE, Huber JD, Rosen CL, Regele JD. Elucidating the role of compression waves and impact duration for generating mild traumatic brain injury in rats. Brain Inj. 2016 Nov 23:1-8. [Epub ahead of print] PubMed PMID: 27880054.

Craniopharyngioma (CP)

Craniopharyngioma (CP)

A craniopharyngioma (CP) is an embryonic malformation of the sellar region and parasellar region.

Its relation to Rathke’s cleft cyst (RCC) is controversial, and both lesions have been hypothesized to lie on a continuum of ectodermal cystic lesions of the sellar region.

Jakob Erdheim (1874-1937) was a Viennese pathologist who identified and defined a category of pituitary tumors known as craniopharyngiomas. He named these lesions “hypophyseal duct tumors” (Hypophysenganggeschwülste), a term denoting their presumed origin from cell remnants of the hypophyseal duct, the embryological structure through which Rathke’s pouch migrates to form part of the pituitary gland. He described the two histological varieties of these lesions as the adamantinomatous and the squamous-papillary types. He also classified the different topographies of craniopharyngiomas along the hypothalamus-pituitary axis. Finally, he provided the first substantial evidence for the functional role of the hypothalamus in the regulation of metabolism and sexual functions. Erdheim’s monograph on hypophyseal duct tumors elicited interest in the clinical effects and diagnosis of pituitary tumors. It certainly contributed to the development of pituitary surgery and neuroendocrinology. Erdheim’s work was greatly influenced by the philosophy and methods of research introduced to the Medical School of Vienna by the prominent pathologist Carl Rokitansky. Routine practice of autopsies in all patients dying at the Vienna Municipal Hospital (Allgemeines Krankenhaus), as well as the preservation of rare pathological specimens in a huge collection stored at the Pathological-Anatomical Museum, represented decisive policies for Erdheim’s definition of a new category of epithelial hypophyseal growths. Because of the generalized use of the term craniopharyngioma, which replaced Erdheim’s original denomination, his seminal work on hypophyseal duct tumors is only referenced in passing in most articles and monographs on this tumor.

Jakob Erdheim should be recognized as the true father of craniopharyngiomas 1).

Epidemiology

Craniopharyngioma epidemiology.

Origin

Its relation to Rathke’s cleft cyst (RCC) is controversial, and both lesions have been hypothesized to lie on a continuum of cystic ectodermal lesions of the sellar region.

It grows close to the optic nerve, hypothalamus and pituitary gland.

Craniopharyngiomas frequently grow from remnants of the Rathke pouch, which is located on the cisternal surface of the hypothalamic region. These lesions can also extend elsewhere in the infundibulohypophyseal axis.

These tumors can also grow from the infundibulum or tuber cinereum on the floor of the third ventricle, developing exclusively into the third ventricle.

Classification

Craniopharyngioma Classification.

Molecular and genetic markers

Genetic and immunological markers show variable expression in different types of Craniopharyngioma. BRAF is implicated in tumorigenesis in papillary Craniopharyngioma (pCP), whereas CTNNB1 and EGFR are often overexpressed in adamantinomatous Craniopharyngioma (aCP) and VEGF is overexpressed in aCP and Craniopharyngioma recurrence. Targeted treatment modalities inhibiting thesepathways can shrink or halt progression of CP. In addition, Epidermal growth factor receptor tyrosine kinase inhibitors may sensitize tumors to radiation therapy. These – drugs show promise in medical management and neoadjuvant therapy for CP. Immunotherapy, including anti-interleukin 6 (IL-6) drugs and interferon treatment, are also effective in managing tumor growth. Ongoing – clinical trials in CP are limited but are testing BRAF/MET inhibitors and IL-6 monoclonal antibodies.

Genetic and immunological markers show variable expression in different subtypes of CP. Several current molecular treatments have shown some success in the management of this disease. Additional clinical trials and targeted therapies will be important to improve CP patient outcomes 2).

Craniopharyngioma Natural History

Craniopharyngioma natural history.

Clinical Features

see Craniopharyngioma Clinical Features.

Diagnosis

see Craniopharyngioma Diagnosis.

Differential diagnosis

Rathke’s cleft cyst.

ependymoma, pilocytic astrocytoma, choroid plexus papilloma (CPP), craniopharyngioma, primitive neuroectodermal tumor (PNET), choroid plexus carcinoma (CPC), immature teratoma, atypical teratoid rhabdoid tumor (AT/RT), anaplastic astrocytoma, and gangliocytoma.

Compared with craniopharyngiomas, sellar gliomas presented with a significantly lower ratio of visual disturbances, growth hormone deficiencies, lesion cystic changes, and calcification. Sellar gliomas had significantly greater effects on the patients’ mentality and anatomical brain stem involvement 3).

Co-occurrence

Simultaneous sellar-suprasellar craniopharyngioma and intramural clival chordoma, successfully treated by a single staged, extended, fully endoscopic endonasal approach, which required no following adjuvant therapy is reported 4).

Treatment

see Craniopharyngioma treatment

Outcome

see Craniopharyngioma outcome

Books

Craniopharyngioma: Surgical Treatment.

10 Selected Works

Craniopharyngioma Selected Works.

Case series

see Craniopharyngioma case series.

Case reports

see Craniopharyngioma case reports.

Videos

Craniopharyngioma Videos

1)

Pascual JM, Rosdolsky M, Prieto R, Strauβ S, Winter E, Ulrich W. Jakob Erdheim (1874-1937): father of hypophyseal-duct tumors (craniopharyngiomas). Virchows Arch. 2015 Jun 19. [Epub ahead of print] PubMed PMID: 26089144.
2)

Reyes M, Taghvaei M, Yu S, Sathe A, Collopy S, Prashant GN, Evans JJ, Karsy M. Targeted Therapy in the Management of Modern Craniopharyngiomas. Front Biosci (Landmark Ed). 2022 Apr 20;27(4):136. doi: 10.31083/j.fbl2704136. PMID: 35468695.
3)

Deng S, Li Y, Guan Y, Xu S, Chen J, Zhao G. Gliomas in the Sellar Turcica Region: A Retrospective Study Including Adult Cases and Comparison with Craniopharyngioma. Eur Neurol. 2014 Dec 18;73(3-4):135-143. [Epub ahead of print] PubMed PMID: 25531372.
4)

Iacoangeli M, Rienzo AD, Colasanti R, Scarpelli M, Gladi M, Alvaro L, Nocchi N, Scerrati M. A rare case of chordoma and craniopharyngioma treated by an endoscopic endonasal, transtubercular transclival approach. Turk Neurosurg.2014;24(1):86-9. doi: 10.5137/1019-5149.JTN.7237-12.0. PubMed PMID: 24535799.

Alzheimer’s disease differential diagnosis with normal pressure hydrocephalus

Alzheimer’s disease differential diagnosis with normal pressure hydrocephalus

Latest PubMED Related Articles

see also Normal pressure hydrocephalus differential diagnosis

Easy and reliable tools for the differential diagnosis between idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer’s disease (AD) are needed.

Callosal angle: On a coronal section at the level of the posterior commissure, this angle is normally 110°; values around 100° are seen in Alzheimer’s disease. In hydrocephalus, the callosal angle is less than 90° as a rule 1)

The degree of dilatation of perihippocampal fissures (PHFs) appears to be a sensitive and specific marker for differentiating AD from NPH by both subjective and objective means, with a very small overlap between the two groups. This observation may have relevance in day-to-day practice 2).

Some of the symptoms of normal pressure hydrocephalus can overlap with those of Alzheimer’s disease, making it an important condition to consider in the differential diagnosis. Here are some points to consider when distinguishing NPH from Alzheimer’s:

Gait disturbances: One of the hallmark symptoms of NPH is gait disturbances, often described as a shuffling walk with small steps and difficulty initiating movement. This symptom is less commonly associated with Alzheimer’s disease.

Urinary incontinence: NPH can cause urinary urgency, frequency, and incontinence. While urinary incontinence can occur in the advanced stages of Alzheimer’s, it is not typically one of the early or prominent symptoms.

Cognitive symptoms: Both NPH and Alzheimer’s disease can cause cognitive impairment, including memory problems and difficulties with attention and concentration. However, in NPH, these cognitive symptoms often occur in combination with gait disturbances and urinary incontinence.

MRI findings: Brain imaging, particularly magnetic resonance imaging (MRI), is useful in differentiating NPH from Alzheimer’s. In NPH, MRI may reveal enlarged ventricles with a characteristic pattern called “ventriculomegaly,” indicating the buildup of cerebrospinal fluid. In contrast, Alzheimer’s disease may show brain atrophy in specific regions.

Response to treatment: Another distinguishing factor is the response to treatment. NPH can often be treated by draining excess cerebrospinal fluid through a surgical procedure called a shunt. If symptoms improve significantly following shunt placement, it suggests NPH rather than Alzheimer’s disease.

It is important to note that NPH and Alzheimer’s disease can coexist in some cases, further complicating the diagnosis. Therefore, a comprehensive evaluation by a healthcare professional, including a detailed medical history, physical examination, cognitive assessments, and neuroimaging, is necessary to differentiate between these conditions accurately.

In a cross-sectional study, iNPH and AD referring to the Neurology Unit of the University of Catania from the 1st of January 2020 to the 1st of December 2022 were enrolled. The following brain linear measurements were calculated: Evans Index (EI), the parieto-occipital Ratio (POR), and the Temporal-Ratio (TR). For each index, sensitivity, specificity, and area under the curve (AUC) were calculated. Moreover, a cumulative index, i.e. the brain linear measurement (BLM) index was also considered.

Fifty patients (25 iNPH and 25 AD) were enrolled. In differentiating iNPH from AD, EI had the highest AUC (0.956), POR had the highest specificity (100%), and TR had the highest sensitivity (92%). The BLM index differentiated iNPH and AD with a sensitivity of 96%, a specificity of 92%, and an AUC of 0.963 with the optimal cut-off value of 0.303.

EI, POR, and TR may be useful in the differential diagnosis between iNPH and AD. At an individual level, the BLM index represents a valid and reliable tool to achieve an accurate differentiation between these two conditions 3)

iNPH patients are present with lower CSF Aβ42 and p-tau concentrations than healthy individuals and lower t-tau and p-tau concentrations than AD patients. This could prove helpful for improving diagnosis, differential diagnosis, and possibly prognosis of iNPH patients 4).

Results suggest that levels of CSF Aβ42, p-tau, and t-tau, in particularly decreased t-tau, are of potential value in differentiating iNPH from LBDs and also confirm previous studies reporting t-tau level is lower and Aβ42 level is higher in iNPH than in AD 5)

A study analyzed and quantified the presence of AQP1 and AQP4 in the CSF of patients with iNPH and AD to determine whether these proteins can be used as biomarkers of iNPH. We examined AQP1 and AQP4 protein levels in the CSF of 179 participants (88 women) classified into 5 groups: possible iNPH (81 participants), hydrocephalus associated with other neurological disorders (13 participants), AD (41 participants), non-AD dementia (32 participants) and healthy controls (12 participants). We recorded each participant’s demographic and clinical variables and indicated, when available in the clinical history, the record of cardiovascular and respiratory complications. An ELISA showed virtually no AQP content in the CSF. Information on the vascular risk factors (available for 61 patients) confirmed some type of vascular risk factor in 86% of the patients with possible iNPH and 58% of the patients with AD. In conclusion, the ELISA analysis showed insufficient sensitivity to detect the presence of AQP1 and AQP4 in CSF, ruling out the possible use of these proteins as biomarkers for diagnosing iNPH 6)

1)

Kiefer M, Unterberg A. The differential diagnosis and treatment of normal-pressure hydrocephalus. Dtsch Arztebl Int. 2012 Jan;109(1-2):15-25; quiz 26. doi: 10.3238/arztebl.2012.0015. Epub 2012 Jan 9. PMID: 22282714; PMCID: PMC3265984.
2)

Holodny AI, Waxman R, George AE, Rusinek H, Kalnin AJ, de Leon M. MR differential diagnosis of normal-pressure hydrocephalus and Alzheimer disease: significance of perihippocampal fissures. AJNR Am J Neuroradiol. 1998 May;19(5):813-9. PMID: 9613493; PMCID: PMC8337558.
3)

Luca A, Donzuso G, Mostile G, Terranova R, Cicero CE, Nicoletti A, Zappia M. Brain linear measurements for differentiating Normal Pressure Hydrocephalus from Alzheimer’s disease: an exploratory study. Eur J Neurol. 2023 Jun 2. doi: 10.1111/ene.15904. Epub ahead of print. PMID: 37265410.
4)

Pyrgelis ES, Boufidou F, Constantinides VC, Papaioannou M, Papageorgiou SG, Stefanis L, Paraskevas GP, Kapaki E. Cerebrospinal Fluid Biomarkers in iNPH: A Narrative Review. Diagnostics (Basel). 2022 Nov 28;12(12):2976. doi: 10.3390/diagnostics12122976. PMID: 36552981; PMCID: PMC9777226.
5)

Said HM, Kaya D, Yavuz I, Dost FS, Altun ZS, Isik AT. A Comparison of Cerebrospinal Fluid Beta-Amyloid and Tau in Idiopathic Normal Pressure Hydrocephalus and Neurodegenerative Dementias. Clin Interv Aging. 2022 Apr 11;17:467-477. doi: 10.2147/CIA.S360736. PMID: 35431542; PMCID: PMC9012339.
6)

Hiraldo-González L, Trillo-Contreras JL, García-Miranda P, Pineda-Sánchez R, Ramírez-Lorca R, Rodrigo-Herrero S, Blanco MO, Oliver M, Bernal M, Franco-Macías E, Villadiego J, Echevarría M. Evaluation of aquaporins in the cerebrospinal fluid in patients with idiopathic normal pressure hydrocephalus. PLoS One. 2021 Oct 1;16(10):e0258165. doi: 10.1371/journal.pone.0258165. PMID: 34597351; PMCID: PMC8486078.

Glioblastoma immunotherapy

Glioblastoma immunotherapy

Immunotherapy has shown promising success in a variety of solid tumor types, but efficacy in glioblastoma is yet to be demonstrated. Barriers to the success of immunotherapy in glioblastoma include a heterogeneous tumor cell population, a highly immunosuppressive microenvironment, and the blood-brain barrier, to name a few. Several immunotherapeutic approaches are actively being investigated and developed to overcome these limitations 1)

Immunotherapy approaches include the use of checkpoint inhibitors, chimeric antigen receptor (CAR) T-Cell therapy, vaccine-based approaches, viral vector therapies, and cytokine-based treatment 2)

Future strategies to ameliorate the efficacy of immunotherapy and facilitate clinical translation will be provided to address the unmet medical needs of GBM 3).

With the success of immunotherapy in other aggressive cancers such as advanced melanoma and advanced non-small cell lung cancer, glioblastoma has been brought to the forefront of immunotherapy research 4).

Immunotherapy, has become a promising strategy with the ability to penetrate the blood-brain barrier since the pioneering discovery of lymphatics in the central nervous system.

The anti-tumoral contribution of Gamma delta T cells depends on their activation and differentiation into effectors. This depends on different molecules and membrane receptors, which conditions their physiology. Belghali et al. aimed to determine the phenotypic characteristics of γδT cells in glioblastoma (Glioblastoma) according to five layers of membrane receptors.

Among ten Glioblastoma cases initially enrolled, five of them who had been confirmed by pathological examination and ten healthy controls underwent phenotyping of peripheral γδT cells by flow cytometry, using the following staining: αβTCR, γδTCR, CD3, CD4, CD8, CD16, CD25, CD27, CD28, CD45, CD45RA, CD56, NKG2D, CD272(BTLA) and CD279(PD-1).

Compared to controls, the results showed no significant change in the number of γδT cells. However, they noted a decrease of double-negative (CD4- CD8- ) Tγδ cells and an increase of naive γδT cells, a lack of CD25 expression, a decrease of the expression of CD279, and a remarkable, but not significant increase in the expression of the CD27 and CD28 costimulation markers. Among γδT cell subsets, the number of Vδ2 decreased in Glioblastoma and showed no significant difference in the expression of CD16, CD56, and NKG2D. In contrast, the number of Vδ1 increased in Glioblastoma with overexpression of CD16, CD56, and NKG2D.

The results showed that γδT cells are prone to adopt a pro-inflammatory profile in the Glioblastoma’s context, which suggests that they might be a potential tool to consider in T cell-based glioblastoma immunotherapy. However, this requires additional investigation on a larger sample size 5).

A limited number of phase III trials have been completed for checkpoint inhibitor, vaccine, as well as gene therapies, and have been unable to show improvement in survival outcomes. Nevertheless, these trials have also shown these strategies to be safe and promising with further adaptations. Further large-scale studies for chimeric antigen receptors T cell therapies and viral therapies are anticipated. Many current trials are broadening the number of antigens targeted and modulating the microtumor microenvironment to abrogate early mechanisms of resistance. Future Glioblastoma treatment will also likely require synergistic effects by combination regimens 6).

As the pioneer and the main effector cells of immunotherapy, T cells play a key role in tumor immunotherapy.

For glioblastoma, immunotherapy has not been as effective 7) , the T cells in Glioblastoma microenvironment are inhibited by the highly immunosuppressive environment of Glioblastoma, (cold tumor microenvironment) posing huge challenges to T cell-based Glioblastoma immunotherapy 8) 9) 10).

As these tumors do not attract and activate immune cells, approaches based on educating immune cells on killing tumor cells, utilized in “hot” immuno-activating cancers, have not been successful in brain tumor clinical trials. In this context, the use of immune-stimulatory approaches, like therapy with oncolytic viruses (OV), is promising 11)

Xu et al. detailed the management of gliomas and previous studies assessing different immunotherapies in gliomas, despite the fact that the associated clinical trials have not been completed yet. Moreover, several drugs that have undergone clinical trials are listed as novel strategies for future application; however, these clinical trials have indicated limited efficacy in glioma. Therefore, additional studies are warranted to evaluate novel therapeutic approaches in glioma treatment 12).

Earlier forms of immune-based platforms have now given way to more current approaches, including chimeric antigen receptor T-cells, personalized neoantigen vaccines, oncolytic viruses, and checkpoint blockade 13).

Critical to mapping a path forward will be the systematic characterization of the immunobiology of glioblastoma utilizing currently available, state of the art technologies. Therapeutic approaches aimed at driving effector immune cells into the glioblastoma microenvironment as well as overcoming immunosuppressive myeloid cells, physical factors, and cytokines, as well as limiting the potentially detrimental, iatrogenic impact of dexamethasone, will likely be required for the potential of anti-tumor immune responses to be realized for glioblastoma 14).

Patients with glioblastoma (Glioblastoma) exhibit a complex state of immunodeficiency involving multiple mechanisms of local, regional, and systemic immune suppression and tolerance. These pathways are now being identified and their relative contributions explored. Delineating how these pathways are interrelated is paramount to effectively implementing immunotherapy for Glioblastoma 15).

Progress in the development of these therapies for glioblastoma has been slow due to the lack of immunogenic antigen targets that are expressed uniformly and selectively by gliomas.

Trials have revealed promising trends in overall survival and progression free survival for patients with glioblastoma, and have paved the way for ongoing randomized controlled trials 16) 17)

Some clinical trials are reaching phase III. Significant progress has been made in unraveling the molecular and genetic heterogeneity of glioblastoma multiforme and its implications to disease prognosis. There is now consensus related to the critical need to incorporate tumor heterogeneity into the design of therapeutic approaches. Recent data also indicates that an efficacious treatment strategy will need to be combinatorial and personalized to the tumor genetic signature 18).

A recurrent theme of this work is that immunotherapy is not a one-size-fits-all solution. Rather, dynamic, tumor-specific interactions within the tumor microenvironment continually shape the immunologic balance between tumor elimination and escape. High-grade gliomas are a particularly fascinating example. These aggressive, universally fatal tumors are highly resistant to radiation and chemotherapy and inevitably recur after surgical resection. Located in the immune-privileged central nervous system, high-grade gliomas also employ an array of defenses that serve as direct impediments to immune attack. Despite these challenges, vaccines have shown activity against high-grade gliomas and anecdotal, preclinical, and early clinical data bolster the notion that durable remission is possible with immunotherapy. Realizing this potential, however, will require an approach tailored to the unique aspects of glioma biology 19).

Clinical experiences with active specific immunotherapy demonstrate feasibility, safety and most importantly, but incompletely understood, prolonged long-term survival in a fraction of the patients. In relapsed patients, Van Gool et al developed an immunotherapy schedule and categorized patients into clinically defined risk profiles. He learned how to combine immunotherapy with standard multimodal treatment strategies for newly diagnosed glioblastoma multiforme patients. The developmental program allows further improvements related to newest scientific insights. Finally, he developed a mode of care within academic centers to organize cell therapy for experimental clinical trials in a large number of patients 20).

Immunostimulating oligodeoxynucleotides containing unmethylated cytosine–guanosine motifs (CpG-ODN) have shown a promising efficacy in several cancer models when injected locally. A previous phase II study of CpG-ODN in patients with Glioblastoma recurrence (Glioblastoma) has suggested some activity and has shown a limited toxicity. This multicentre single-blinded randomised phase II trial was designed to study the efficacy of a local treatment by CpG-ODN in patients with de novo glioblastomas.

Patients with a newly diagnosed glioblastoma underwent large surgical resection and CpG-ODN was randomly administrated locally around the surgical cavity. The patients were then treated according to standard of care (SOC) with radiotherapy and temozolomide. The primary objective was 2-year survival. Secondary outcomes were progression free survival (PFS), and tolerance.

Eighty-one (81) patients were randomly assigned to receive CpG-ODN plus SOC (39 patients) or SOC (42 patients). The 2-year overall survival was 31% (19%; 49%) in the CpG-ODN arm and 26% (16%; 44%) in the SOC arm. The median PFS was 9 months in the CpG-ODN arm and 8.5 months in the SOC arm. The incidence of adverse events was similar in both arms; although fever and post-operative haematoma were more frequent in the CpG-ODN arm.

Local immunotherapy with CpG-ODN injected into the surgical cavity after tumour removal and followed by SOC, although well tolerated, does not improve survival of patients with newly diagnosed Glioblastoma 21).

Epidermal growth factor receptor 3 (EGFRvIII) is present in approximately one-third of glioblastoma (Glioblastoma) patients. It is never found in normal tissues; therefore, it represents a candidate target for glioblastoma immunotherapy. PEPvIII, a peptide sequence from EGFRvIII, was designed to represent a target of glioma and is presented by MHC I/II complexes. Dendritic cells (DCs) have great potential to sensitize CD4+ T and CD8+ T cells to precisely target and eradicate Glioblastoma.

Li et al. show that PEPvIII could be loaded by DCs and presented to T lymphocytes, especially PEPvIII-specific CTLs, to precisely kill U87-EGFRvIII cells. In addition to inhibiting proliferation and inducing the apoptosis of U87-EGFRvIII cells, miR-326 also reduced the expression of TGF-β1 in the tumour environment, resulting in improved efficacy of T cell activation and killing via suppressing the SMO/Gli2 axis, which at least partially reversed the immunosuppressive environment. Furthermore, combining the EGFRvIII-DC vaccine with miR-326 was more effective in killing U87-EGFRvIII cells compared with the administration of either one alone. This finding suggested that a DC-based vaccine combined with miR-326 may induce more powerful anti-tumour immunity against Glioblastoma cells that express a relevant antigen, which provides a promising approach for Glioblastoma immunotherapy 22).

Reviews

Yuan et al. provided an overview of the basic knowledge underlying immune targeting and promising immunotherapeutic strategies including CAR T cells, oncolytic viruses, cancer vaccines, and checkpoint blockade inhibitors that have been recently investigated in glioblastoma. Current clinical trials and previous clinical trial findings are discussed, shedding light on novel strategies to overcome various limitations and challenges 23).

Rui Y, Green JJ. Overcoming delivery barriers in immunotherapy for glioblastoma. Drug Deliv Transl Res. 2021 May 30. doi: 10.1007/s13346-021-01008-2. Epub ahead of print. PMID: 34053034.

Glioblastoma Immune Checkpoint Inhibitor Therapy

Glioblastoma Immune Checkpoint Inhibitor Therapy

Glioblastoma CAR-T cell therapy

Glioblastoma CAR-T cell therapy

1)

Zaidi SE, Moelker E, Singh K, Mohan A, Salgado MA, Essibayi MA, Hotchkiss K, Shen S, Lee W, Sampson J, Khasraw M. Novel Immunotherapeutic Approaches for the Treatment of Glioblastoma. BioDrugs. 2023 May 31. doi: 10.1007/s40259-023-00598-2. Epub ahead of print. PMID: 37256535.
2)

Sener U, Ruff MW, Campian JL. Immunotherapy in Glioblastoma: Current Approaches and Future Perspectives. Int J Mol Sci. 2022 Jun 24;23(13):7046. doi: 10.3390/ijms23137046. PMID: 35806051; PMCID: PMC9266573.
3)

Bausart M, Préat V, Malfanti A. Immunotherapy for glioblastoma: the promise of combination strategies. J Exp Clin Cancer Res. 2022 Jan 25;41(1):35. doi: 10.1186/s13046-022-02251-2. PMID: 35078492; PMCID: PMC8787896.
4)

Yu MW, Quail DF. Immunotherapy for Glioblastoma: Current Progress and Challenges. Front Immunol. 2021 May 13;12:676301. doi: 10.3389/fimmu.2021.676301. Erratum in: Front Immunol. 2021 Oct 07;12:782687. PMID: 34054867; PMCID: PMC8158294.
5)

Belghali MY, El Moumou L, Hazime R, Brahimi M, El Marrakchi M, Belaid HA, Benali SA, Khouchani M, Ba-M’hamed S, Admou B. Phenotypic characterization of human peripheral γδT-Cell subsets in glioblastoma. Microbiol Immunol. 2022 Jun 19. doi: 10.1111/1348-0421.13016. Epub ahead of print. PMID: 35718749.
6)

Zhang M, Choi J, Lim M. Advances in Immunotherapies for Gliomas. Curr Neurol Neurosci Rep. 2022 Feb 2. doi: 10.1007/s11910-022-01176-9. Epub ahead of print. PMID: 35107784.
7)

Bovenberg MS, Degeling MH, Tannous BA. Cell-based immunotherapy against gliomas: from bench to bedside. Mol Ther. 2013 Jul;21(7):1297-305. doi: 10.1038/mt.2013.80. Epub 2013 May 7. PMID: 23648695; PMCID: PMC3702108.
8)

Wang H, Zhou H, Xu J, Lu Y, Ji X, Yao Y, Chao H, Zhang J, Zhang X, Yao S, Wu Y, Wan J. Different T-cell subsets in glioblastoma multiforme and targeted immunotherapy. Cancer Lett. 2020 Oct 3:S0304-3835(20)30498-5. doi: 10.1016/j.canlet.2020.09.028. Epub ahead of print. PMID: 33022290.
9)

Lim M., Xia Y., Bettegowda C., Weller M. Current state of immunotherapy for glioblastoma. Nat. Rev. Clin. Oncol. 2018;15:422–442. doi: 10.1038/s41571-018-0003-5.
10)

Reardon D.A., Wucherpfennig K., Chiocca E.A. Immunotherapy for glioblastoma: On the sidelines or in the game? Discov. Med. 2017;24:201–208.
11)

Iorgulescu JB, Reardon DA, Chiocca EA, Wu CJ. Immunotherapy for glioblastoma: going viral. Nat Med. 2018 Aug;24(8):1094-1096. doi: 10.1038/s41591-018-0142-3. PMID: 30082860; PMCID: PMC6443579.
12)

Xu S, Tang L, Li X, Fan F, Liu Z. Immunotherapy for glioma: current management and future application. Cancer Lett. 2020 Feb 7. pii: S0304-3835(20)30056-2. doi: 10.1016/j.canlet.2020.02.002. [Epub ahead of print] PubMed PMID: 32044356.
13)

Fecci PE, Sampson JH. The current state of immunotherapy for gliomas: an eye toward the future. J Neurosurg. 2019 Sep 1;131(3):657-666. doi: 10.3171/2019.5.JNS181762. Review. PubMed PMID: 31473668.
14)

Reardon DA, Wucherpfennig K, Chiocca EA. Immunotherapy for glioblastoma: on the sidelines or in the game? Discov Med. 2017 Nov;24(133):201-208. PubMed PMID: 29278673.
15)

Jackson CM, Lim M. Immunotherapy for glioblastoma: playing chess, not checkers. Clin Cancer Res. 2018 Apr 24. pii: clincanres.0491.2018. doi: 10.1158/1078-0432.CCR-18-0491. [Epub ahead of print] PubMed PMID: 29691293.
16)

Thomas AA, Fisher JL, Ernstoff MS, Fadul CE. Vaccine-based immunotherapy for glioblastoma. CNS Oncol. 2013 Jul;2(4):331-49. doi: 10.2217/cns.13.29. PubMed PMID: 25054578.
17)

Agrawal NS, Miller R Jr, Lal R, Mahanti H, Dixon-Mah YN, DeCandio ML, Vandergrift WA 3rd, Varma AK, Patel SJ, Banik NL, Lindhorst SM, Giglio P, Das A. Current Studies of Immunotherapy on Glioblastoma. J Neurol Neurosurg. 2014 Apr 5;1(1). pii: 21000104. PubMed PMID: 25346943.
18)

Kamran N, Calinescu A, Candolfi M, Chandran M, Mineharu Y, Assad AS, Koschmann C, Nunez F, Lowenstein P, Castro M. Recent advances and future of immunotherapy for glioblastoma. Expert Opin Biol Ther. 2016 Jul 13. [Epub ahead of print] PubMed PMID: 27411023.
19)

Jackson CM, Lim M, Drake CG. Immunotherapy for Brain Cancer: Recent Progress and Future Promise. Clin Cancer Res. 2014 Apr 25. [Epub ahead of print] PubMed PMID: 24771646.
20)

Van Gool SW. Brain Tumor Immunotherapy: What have We Learned so Far? Front Oncol. 2015 Jun 17;5:98. eCollection 2015. Review. PubMed PMID: 26137448.
21)

Ursu R, Carpentier A, Metellus P, Lubrano V, Laigle-Donadey F, Capelle L, Guyotat J, Langlois O, Bauchet L, Desseaux K, Tibi A, Chinot O, Lambert J, Carpentier AF. Intracerebral injection of CpG oligonucleotide for patients with de novo glioblastoma-A phase II multicentric, randomised study. Eur J Cancer. 2017 Jan 28;73:30-37. doi: 10.1016/j.ejca.2016.12.003. [Epub ahead of print] PubMed PMID: 28142059.
22)

Li J, Wang F, Wang G, Sun Y, Cai J, Liu X, Zhang J, Lu X, Li Y, Chen M, Chen L, Jiang C. Combination epidermal growth factor receptor variant III peptide-pulsed dendritic cell vaccine with miR-326 results in enhanced killing on EGFRvIII-positive cells. Oncotarget. 2017 Feb 17. doi: 10.18632/oncotarget.15445. [Epub ahead of print] PubMed PMID: 28412740.
23)

Yuan B, Wang G, Tang X, Tong A, Zhou L. Immunotherapy of glioblastoma: recent advances and future prospects. Hum Vaccin Immunother. 2022 Mar 28:1-16. doi: 10.1080/21645515.2022.2055417. Epub ahead of print. PMID: 35344682.

Decompressive craniectomy for intracranial hypertension treatment

Decompressive craniectomy for intracranial hypertension treatment

.

Decompressive craniectomy for traumatic brain injury

see Decompressive craniectomy for severe traumatic brain injury indications.

Decompressive craniectomy for ischemic stroke

see Decompressive craniectomy for ischemic stroke indications.

Decompressive craniectomy for intracerebral hemorrhage

Decompressive craniectomy for intracerebral hemorrhage indications.

Suboccipital decompressive craniectomy for cerebellar infarction

Suboccipital decompressive craniectomy for cerebellar infarction.

Peptic ulcer disease

Peptic ulcer disease

Peptic ulcer disease is a condition in which there are painful sores or ulcers in the lining of the stomach or the first part of the small intestine (the duodenum). Normally, a thick layer of mucus protects the stomach lining from the effect of its digestive juices.

A duodenal ulcer is a peptic ulcer that develops in the first part of the small intestine (duodenum). An esophageal ulcer occurs in the lower part of your esophagus.

Etiology

Steroid side effects

In 1932, Harvey Cushing described peptic ulceration secondary to raised intracranial pressure and attributed this to vagal overactivity, causing excess gastric acid secretion. Cushing ulcer remains a cause of morbidity in patients, albeit one that is preventable.

Kumaria et al. evaluate the evidence pertaining to the pathophysiology of neurogenic peptic ulceration. A literature review suggests that the pathophysiology of Cushing ulcer may extend beyond vagal mechanisms for several reasons: (1) clinical and experimental studies have shown only a modest increase in gastric acid secretion in head injury patients; (2) increased vagal tone is found in only a minority of cases of intracranial hypertension, most of which are related to catastrophic, nonsurvivable brain injury; (3) direct stimulation of the vagus nerve does not cause peptic ulceration, and; (4) Cushing ulcer can occur after acute ischemic stroke, but only a minority of strokes are associated with raised intracranial pressure and/or increased vagal tone. The 2005 Nobel Prize in Medicine honored the discovery that bacteria play key roles in the pathogenesis of peptic ulcer disease. Brain injury results in widespread changes in the gut microbiome in addition to gastrointestinal inflammation, including systemic upregulation of proinflammatory cytokines. Alterations in the gut microbiome in patients with severe traumatic brain injury include colonization with commensal flora associated with peptic ulceration. The brain-gut-microbiome axis integrates the central nervous system, the enteric nervous system, and the immune system.

They propose a novel hypothesis that neurogenic peptic ulcer may be associated with alterations in the gut microbiome, resulting in gastrointestinal inflammation leading to ulceration 1).

Treatment

Omeprazole for Adults with peptic ulcers or gastroesophageal reflux disease (GERD) 20–40 mg PO daily. For Zollinger-Ellison syndrome: 20 mg PO q d to 120 mg PO TID (dose adjusted to keep basal acid output < 60 mEq/hr).

Side effects: N/V, H/A, diarrhea, abdominal pain, or rash in 1–5% of patients. Supplied: 10, 20 & 40 mg delayed-release capsules. Available OTC in 20.6 mg tablets as Prilosec OTC.

Misoprostol (Cytotec®), a prostaglandin, may be effective in mitigating NSAID-induced gastric erosion or peptic ulcer. Contraindicated in pregnancy. ℞ 200 mcg PO QID with food as long as the patient is on NSAIDs. If not tolerated, use 100 mcg. ✖ CAUTION: an abortifacient. Should not be given to pregnant women or women of childbearing potential

1)

Kumaria A, Kirkman MA, Scott RA, Dow GR, Leggate AJ, Macarthur DC, Ingale HA, Smith SJ, Basu S. A Reappraisal of the Pathophysiology of Cushing Ulcer: A Narrative Review. J Neurosurg Anesthesiol. 2023 May 11. doi: 10.1097/ANA.0000000000000918. Epub ahead of print. PMID: 37188653.

Carotid artery stenting (CAS)

Carotid artery stenting (CAS)

Latest Pubmed Carotid artery stenting Related Articles

Common carotid artery stenting is a medical procedure performed to treat carotid artery stenosis, which is the narrowing of the carotid arteries that supply blood to the brain. It is a less invasive alternative to carotid endarterectomy, a surgical procedure used for the same purpose.

During common carotid artery stenting, a thin, flexible tube called a catheter is inserted into an artery, usually in the groin, and guided up to the site of the carotid artery stenosis. Using X-ray guidance, the catheter is advanced to the affected area. Once in position, a small, expandable mesh tube called a stent is placed at the site of the stenosis. The stent is then expanded, pushing against the walls of the artery, and helps to keep the artery open.

The stent acts as a scaffold, improving blood flow through the carotid artery and reducing the risk of stroke. Some stents are designed with a filter or a protective device to capture any debris that may break loose during the procedure, preventing it from reaching the brain.

Common carotid artery stenting is typically performed under local anesthesia, meaning the patient is awake but the area being treated is numbed. It is often considered for patients who are at high risk for complications from carotid endarterectomy, such as those with previous neck surgery, radiation therapy, or significant medical comorbidities.

Like any medical procedure, common carotid artery stenting carries some risks, including the potential for blood vessel injury, stroke, infection, or allergic reactions to contrast dye used during the procedure. However, it is generally considered safe and effective when performed by experienced medical professionals.

Indications

Carotid artery stenting is indicated for the treatment of carotid artery stenosis, which is the narrowing of the carotid arteries that supply blood to the brain. The procedure may be recommended in certain situations, depending on the severity of the stenosis and the patient’s overall health. The main indications for carotid artery stenting include:

Symptomatic Carotid Artery Stenosis: Carotid artery stenting is commonly recommended for patients who have experienced symptoms related to carotid artery stenosis, such as a transient ischemic attack (TIA) or a minor stroke. These symptoms may include temporary vision loss, weakness or numbness on one side of the body, difficulty speaking, or dizziness. In such cases, carotid artery stenting aims to reduce the risk of future stroke by improving blood flow through the carotid arteries.

Asymptomatic Carotid Artery Stenosis: Carotid artery stenting may also be considered in certain cases of asymptomatic carotid artery stenosis, particularly when the stenosis is severe (greater than 70% narrowing). The decision to proceed with stenting in asymptomatic cases is often based on factors such as the patient’s age, overall health, life expectancy, and the presence of other risk factors for stroke.

High-Risk Candidates for Carotid Endarterectomy (CEA): Carotid artery stenting is sometimes recommended for patients who are at high risk for complications from carotid endarterectomy, which is a surgical procedure used to treat carotid artery stenosis. High-risk factors may include previous neck surgery, radiation therapy to the neck, severe heart or lung disease, or advanced age. Carotid artery stenting is considered a less invasive alternative for these patients.

It is important to note that the decision to undergo carotid artery stenting should be made on an individual basis, taking into consideration the patient’s specific medical condition, overall health, and the expertise of the healthcare team. A thorough evaluation by a vascular specialist or a neurologist is typically conducted to determine the most appropriate treatment approach for each patient.

Carotid artery angioplasty and stenting (CAS) has experienced an astonishing rate of development, becoming a viable alternative to carotid endarterectomy (CEA) in the management of carotid artery stenosis. Many trials have attempted to compare both treatment modalities and establish indications for each, depending on clinical and anatomic features.

Eller et al. review the historical evolution of carotid stenting; its main technical aspects, indications, and contraindications; as well as the most important clinical trials comparing CAS and CEA 1).

Primary carotid stenting, performed using self-expanding stents alone without deliberate use of embolic protection devices and balloon angioplasty, has been shown to be effective and faster, cheaper, and potentially safer than conventional techniques.

see also Bilateral carotid artery stenting.

Carotid artery stenting (CAS) is a neuroendovascular treatment where a stent is deployed within the lumen of the carotid artery to prevent a stroke by treating carotid artery stenosis.

It has emerged as an alternative to carotid endarterectomy. In randomised trials comparing stenting with endarterectomy for symptomatic carotid artery stenosis, stenting was associated with a higher risk of procedure-related stroke, particularly in elderly patients, but with lower risks of myocardial infarction, cranial nerve palsy, and access site haematoma 2) 3) 4) 5).

A systematic review showed that the increase in procedure-related risk was driven by non-disabling stroke, with no evidence for a difference in rates of major or disabling stroke or death between the treatments 6).

Complications

see Carotid artery stenting complications.

Efficacy

see International Carotid Stenting Study.

Residual stenosis after carotid artery stenting

A study investigated the effect of residual stenosis after carotid artery stenting (CAS) on periprocedural and long-term outcomes.

Patients treated with CAS for symptomatic or asymptomatic carotid arterial stenosis were consecutively enrolled. Residual stenosis was estimated from post-procedure angiography findings. The effects of residual stenosis on 30-day periprocedural outcome and times to restenosis and clinical outcome were analyzed using logistic regression models and Wei-Lin-Weissfeld models, respectively.

A total of 412 patients (age, 64.7 ± 17.0 years; male, 82.0%) were enrolled. The median baseline stenosis was 80% (interquartile range [IQR], 70-90%), which improved to 10% (0-30%) for residual stenosis. Residual stenosis was significantly associated with periprocedural outcome (adjusted odds ratio, 0.983; 95% confidence interval [CI], 0.965-0.999, P = 0.01) after adjustment for baseline stenosis, age, hypertension, symptomaticity, and statin use. Over the 5-year observation period, residual stenosis did not increase the global hazard for restenosis and clinical outcome (adjusted hazard ratio, 1.011; 95% CI, 0.997-1.025. In the event-specific model, residual stenosis increased the hazard for restenosis (adjusted hazard ratio, 1.041; 1.012-1.072) but not for clinical outcome (adjusted hazard ratio, 1.011; 0.997-1.025).

Residual stenosis after carotid artery stenting may be useful to predict periprocedural outcome and restenosis 7).

Case series

see Carotid artery stenting case series.

Case reports

Endovascular revascularization of a stenotic lesion requires appropriate stent positioning. In particular, stenting of the common carotid artery (CCA) ostium makes it difficult to avoid proptosis into the aorta. Furthermore, the guiding catheter may become unstable during the stenting because of its position under the aortic arch. To resolve these problems, Terakado et al. performed antegrade stenting for a patient with a symptomatic stenotic left CCA ostium that was treated by lifting a balloon-guiding catheter with a gooseneck snare. A patient was a 74-year-old man who presented to the hospital with main complaints of right hemiparesis and motor aphasia. A left cerebral infarction due to severe stenotic left CCA ostium was diagnosed. A CT perfusion study showed decreased cerebral blood flow in the left hemisphere. Stenting of the stenotic left CCA ostium was performed using an antegrade approach. A balloon-guiding catheter positioned under the aortic arch was inflated and lifted from the right brachiocephalic artery using a gooseneck snare. The guiding catheter was stabilized during stenting. This method is highly effective for stenting CCA ostium 8)

A 68-year-old man was admitted. Neurological examination revealed severe left-sided motor weakness. Magnetic resonance imaging showed no cerebral infarction, but magnetic resonance angiography revealed complete occlusion of the right internal carotid artery. Systemic intravenous injection of recombinant tissue plasminogen activator was performed within 4h after the onset. But, magnetic resonance angiography still revealed complete occlusion. Revascularization of the right cervical internal carotid artery was performed via endovascular surgery. The occluded artery was successfully recanalized using the Penumbra System® and stent placement at the origin of the internal carotid artery. Immediately after surgery, dual antiplatelet therapy (aspirin and clopidogrel) was initiated, and then cilostazol was added on the following day. Carotid ultrasonography and three-dimensional computed tomographic angiography at 14days revealed no further obstruction to flow.

When trying to perform emergency carotid artery stenting within 24h after intravenous recombinant tissue plasminogen activator administration, several issues require attention, such as the decisions regarding the type of stent and embolic protection device, the selection of antiplatelet therapy and the methods of preventing hyperperfusion syndrome.

Emergency carotid artery stenting for the acute internal carotid artery occlusion may be considered a safe procedure in preventing early stroke recurrence in selected patients 9).

References

1)

Eller JL, Snyder KV, Siddiqui AH, Levy EI, Hopkins LN. Endovascular treatment of carotid stenosis. Neurosurg Clin N Am. 2014 Jul;25(3):565-82. doi: 10.1016/j.nec.2014.04.012. Epub 2014 Jun 2. PubMed PMID: 24994091.
2)

Mas JL, Chatellier G, Beyssen B, et al. Endarterectomy versus stenting in patients with symptomatic severe carotid stenosis. N Engl J Med 2006; 355: 1660–71.
3)

The SPACE Collaborative Group. 30 day results from the SPACE trial of stent-protected angioplasty versus carotid endarterectomy in symptomatic patients: a randomised non-inferiority trial. Lancet 2006; 368: 1239–47.
4)

International Carotid Stenting Study investigators. Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial. Lancet 2010; 375: 985–97.
5)

Brott TG, Hobson RW, Howard G, et al. Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med 2010; 363: 11–23.
6)

Bonati LH, Lyrer P, Ederle J, Featherstone R, Brown MM. Percutaneous transluminal balloon angioplasty and stenting for carotid artery stenosis. Cochrane Database Syst Rev 2012; 9: CD000515.
7)

Kang J, Hong JH, Kim BJ, Bae HJ, Kwon OK, Oh CW, Jung C, Lee JS, Han MK. Residual stenosis after carotid artery stenting: Effect on periprocedural and long-term outcomes. PLoS One. 2019 Sep 9;14(9):e0216592. doi: 10.1371/journal.pone.0216592. eCollection 2019. PubMed PMID: 31498785.
8)

Terakado T, Matumaru Y, Ishikawa E. Stenting of the Common Carotid Artery Ostium: Balloon Catheter Lifting-Up Technique With a Gooseneck Snare. Vasc Endovascular Surg. 2023 May 22:15385744231178179. doi: 10.1177/15385744231178179. Epub ahead of print. PMID: 37212169.
9)

Inoue A, Kohno K, Fukumoto S, Ozaki S, Ninomiya S, Tomita H, Kamogawa K, Okamoto K, Ichikawa H, Onoue S, Miyazaki H, Okuda B, Iwata S. Importance of perioperative management for emergency carotid artery stenting within 24h after intravenous thrombolysis for acute ischemic stroke: Case report. Int J Surg Case Rep. 2016 Jul 27;26:108-112. doi: 10.1016/j.ijscr.2016.07.027. [Epub ahead of print] PubMed PMID: 27478968.

Intracranial hemorrhage from Dengue

Intracranial hemorrhage from Dengue

Dengue fever is a viral infection caused by the dengue virus, which is primarily transmitted by the Aedes mosquito. The virus belongs to the Flaviviridae family and has four different serotypes: DEN-1, DEN-2, DEN-3, and DEN-4. Dengue is prevalent in tropical and subtropical regions, particularly in urban and semi-urban areas.

Symptoms of dengue fever typically appear within 4 to 7 days after a person is bitten by an infected mosquito. They can range from mild to severe and may include high fever, severe headache, joint and muscle pain, rash, nausea, vomiting, and in some cases, bleeding manifestations.

Complications

Severe forms of dengue, known as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), can cause life-threatening complications such as severe bleeding, organ damage, and circulatory failure.

A rare but possibly dangerous consequence of dengue illness is intracranial hemorrhage (ICH). Currently, the pathogenesis of ICH is unknown.

Treatment

There is no specific antiviral treatment for dengue fever, and management mainly involves supportive care to relieve symptoms and prevent complications. Rest, hydration, and over-the-counter pain relievers such as acetaminophen can help alleviate fever and pain. It is important to avoid medications like aspirin, ibuprofen, and naproxen, as they can increase the risk of bleeding.

Studies have reported the use of emergency surgery while monitoring thrombocytopenia in the therapy of dengue ICH 1).

Prevention

Prevention is crucial in controlling the spread of dengue. Measures include eliminating mosquito breeding sites by emptying standing water containers, using insect repellents, wearing protective clothing, and using mosquito nets or screens. In some high-risk areas, mosquito control programs may be implemented to reduce the mosquito population.

If you suspect you have dengue fever or are in an area with a dengue outbreak, it is advisable to seek medical attention for diagnosis and appropriate management.

Bangladesh reported the highest number of annual deaths (n = 281) related to dengue virus infection in 2022 since the virus reappeared in the country in 2000. Earlier studies showed that >92% of the annual cases occurred between the months of August and September. The 2022 outbreak is characterized by late onset of dengue cases with unusually higher deaths in colder months, that is, October-December. Haider et al. present possible hypotheses and explanations for this late resurgence of dengue cases. First, in 2022, the rainfall started late in the season. Compared to the monthly average rainfall for September and October between 2003 and 2021, there was 137 mm of additional monthly rainfall recorded in September and October 2022. Furthermore, the year 2022 was relatively warmer with a 0.71°C increased temperature than the mean annual temperature of the past 20 yr. Second, a new dengue virus serotype, DENV-4, had recently reintroduced/reappeared in 2022 and become the dominant serotype in the country for a large naïve population. Third, the post-pandemic return of normalcy after 2 yr of nonpharmaceutical social measures facilitates extra mosquito breeding habitats, especially in construction sites. Community engagement and regular monitoring and destruction of Aedes mosquitoes’ habitats should be prioritized to control dengue virus outbreaks in Bangladesh 2).

Case reports

A 65-year-old man who presented with dengue fever symptoms and developed altered consciousness and focal neurological deficits. The findings of the tests showed thrombocytopenia, increased AST and ALT, positive anti-dengue IgG, and subdural hematoma on brain imaging. The urgent operations were completed satisfactorily.

Dengue-related intracerebral haemorrhage is still a complicated condition. Thrombocytopenia and leukopenia are the first symptoms that point to dengue. Some risk factors, such as thrombocytopenia and increased AST and ALT, have been identified as bleeding factors in dengue fever. For a possible intracerebral haemorrhage, radiological imaging should be performed. In an emergency neurosurgery setting, thrombocyte administration could be used to monitor thrombocytopenia.

Subdural hematoma is a possible dengue fever complication. If the patient’s symptoms with thrombocytopenia and elevated liver enzymes indicate the possibility of intracranial haemorrhage, immediate radiological imaging should be performed 3)

A 65-year-old male patient was admitted with high-grade febrile illness and diagnosed with dengue. The patient had no focal neurology and was managed adequately following the primary survey on admission but, then, developed severe thrombocytopenia and eventually the critical phase of dengue illness. On the 5th admission day, the patient collapsed. Glasgow Coma Score was 3/15 with bilaterally dilated, fixed pupils. Immediate computed tomography head revealed a large left SDH with a significant midline shift. SDH was emergently evacuated with two units of platelets transfused peroperatively and two additional units postoperatively. Thrombocytopenia resolved within 48 h, and interval scanning showed gradual resolution of SDH. The patient was discharged 18 days later. Five months later, on follow-up, the patient is well with mild left-sided weakness and an Extended Glasgow Outcome Score of 7.

Isolated SDH is a rare but life-threatening hemorrhagic complication of DHF. Even in the critical phase of illness, with severe thrombocytopenia, surgical evacuation should be considered if the SDH is present in isolation, within an accessible area, and can be operated on immediately 4).

A 48-year-old Indian woman presented with fever and body aches followed by acute onset of paraplegia with bladder and bowel dysfunction and loss of sensations below the level of the umbilicus. She had severe thrombocytopenia and positive dengue serology. Magnetic resonance imaging of the spine showed compression of the spinal cord due to intradural hematoma at the D7-D8 vertebral level. The patient received symptomatic treatment for dengue fever and steroids. Emergency D7-D8 laminectomy with excision of the clot and dural repair was done after stabilizing the platelet count with multiple platelet transfusions. The constitutional symptoms responded well to the treatment. There was good improvement in sensory symptoms but negligible improvement in paraplegia with a change in muscle power from grade 0/5 to grade 1/5 in the postoperative period. The patient was discharged from the hospital in a stable condition, but paraplegia showed little improvement during follow-up of 1 year.

Spontaneous spinal cord hemorrhage can present as acute paraplegia in dengue fever. Failure to recognize this complication can delay initiating appropriate treatment with permanent loss of neurologic function 5).

A 18-year-old Pakistani male, presented with fever, colicky abdominal pain, vomiting, diarrhea, dark-colored urine, and oliguria.

Diagnoses: Dengue rapid NS-1 test came back positive. Along with myoglobinuria both serum creatine phosphokinase and creatine levels were abnormal. Hence, the patient was diagnosed with rhabdomyolysis-induced acute kidney injury. On physical examination, his right arm was painful and tender with restricted movement at the elbow. A Doppler ultrasound of the arm revealed thickening of the skin and underlying muscles, as well as edematous abnormalities affecting the entire right upper limb, both of which are indications of compartment syndrome.

Interventions and outcome: The management included rehydration, administration of dextrose and bicarbonate (bicarbonate infusion) prepared by adding 150 mEq sodium bicarbonate in 850 mL dextrose 5%, pain killers, along with platelet, and packed red cell transfusions. Additionally, right upper limb was kept elevated at 90° for 30 minutes every 2 hours to reduce edema and crept bandages were applied. The patient was discharged after 11 days and the follow-up was uneventful.

Lesson: Physicians should be aware that rhabdomyolysis-induced acute kidney damage and limb compartment syndrome are also possible DF consequences, and they should be on the lookout for any indications pointing to these complications in DF. A prompt diagnosis can prevent further complications and fatality 6).

Four patients referred for neurosurgical intervention as sequelae to dengue coagulopathy. Among them, three had intracranial bleeds and one had spinal cord hematoma along with intracranial hemorrhages. This small series includes the youngest reported case of dengue coagulopathy with intracranial bleed and only the second case of spontaneous intraspinal hematoma sequelae to dengue hemorrhagic fever. The situations where patients contract dengue in a setting of neurosurgical intervention are grave. The margin of safety in the presence of dengue coagulopathy is narrow. The surgeon has to outweigh benefit against risk of surgery in each individual. A subdural and intramedullary spinal cord hematoma, which was summarized in the article “Burden of Dengue related neurosurgical emergencies during an epidemic- A tertiary care experience 7)

A report of quadriparesis in dengue fever due to hematomyelia 8).

The first report of intradural spinal hematoma secondary to dengue was reported by Kaur et al 9).

A patient with dengue fever with symptoms suggestive of acute flaccid paralysis, and on subsequent investigation he was diagnosed as a case of hypokalaemic quadriparesis. Clinicians in the endemic area should be aware of such association of acute pure motor reversible quadriparesis with dengue fever 10).

Dengue infection causing acute hypokalemic quadriparesis 11).

1)

Siahaan AMP, Tandean S, Nainggolan BWM, Tarigan J, Sitanggang JS. A Critical Analysis of Intracranial Hemorrhage (ICH) as a Fatal Complication of Dengue Fever. J Korean Neurosurg Soc. 2023 Jan 16. doi: 10.3340/jkns.2022.0205. Epub ahead of print. PMID: 36642946.
2)

Haider N, Hasan MN, Khalil I, Tonge D, Hegde S, Chowdhury MAB, Rahman M, Hossain Khan M, Ansumana R, Zumla A, Uddin MJ. The 2022 dengue outbreak in Bangladesh: hypotheses for the late resurgence of cases and fatalities. J Med Entomol. 2023 May 18:tjad057. doi: 10.1093/jme/tjad057. Epub ahead of print. PMID: 37202843.
3)

Siahaan AMP, Tandean S, Saragih EB, Nainggolan BWM. Spontaneous acute subdural hematoma in dengue fever: Case report and review of the literature. Int J Surg Case Rep. 2022 Sep;98:107512. doi: 10.1016/j.ijscr.2022.107512. Epub 2022 Aug 13. PMID: 35985111; PMCID: PMC9411658.
4)

Ashraf M, Hussain SS, Farooq M, Fatima L, Majeed N, Ashraf N. Isolated subdural hematoma due to dengue hemorrhagic fever: Surgical intervention and review of the literature. Surg Neurol Int. 2022 Jun 10;13:244. doi: 10.25259/SNI_334_2022. PMID: 35855175; PMCID: PMC9282807.
5)

Kaushik RM, Kumar R, Kaushik M, Saini M, Kaushik R. Spontaneous spinal intradural hemorrhage in dengue fever: a case report. J Med Case Rep. 2022 May 30;16(1):213. doi: 10.1186/s13256-022-03451-2. PMID: 35644613; PMCID: PMC9150361.
6)

Arif A, Abdul Razzaque MR, Kogut LM, Tebha SS, Shahid F, Essar MY. Expanded dengue syndrome presented with rhabdomyolysis, compartment syndrome, and acute kidney injury: A case report. Medicine (Baltimore). 2022 Feb 18;101(7):e28865. doi: 10.1097/MD.0000000000028865. PMID: 35363190; PMCID: PMC9281986.
7)

Kutty RK, Sreemathyamma SB, Sivanandapanicker JL, Mundhe V, Chhabra K, Peethambaran A. Burden of Dengue-related Neurosurgical Emergencies during an Epidemic: A Tertiary Care Experience. Asian J Neurosurg. 2019 Jan-Mar;14(1):211-218. doi: 10.4103/ajns.AJNS_318_17. PMID: 30937037; PMCID: PMC6417330.
8)

Kumar MS, Srinanthini KR, Gopal S. A report of quadriparesis in dengue fever due to hematomyelia. Neurol India. 2019 Mar-Apr;67(2):530-531. doi: 10.4103/0028-3886.258054. PMID: 31085871.
9)

Kaur J, Virk JS, Paul BS, Saggar K. Dengue fever presenting as cauda equina syndrome. BMJ Case Rep. 2017 Jul 24;2017:bcr2017221251. doi: 10.1136/bcr-2017-221251. PMID: 28739570; PMCID: PMC5624003.
10)

Gupta DK, Vaish AK, Arya RK, Chaudhary SC. Hypokalaemic quadriparesis: an unusual manifestation of dengue fever. BMJ Case Rep. 2011 Jun 17;2011:bcr1220103673. doi: 10.1136/bcr.12.2010.3673. PMID: 22692495; PMCID: PMC3118907.
11)

Gulati S. Dengue infection causing acute hypokalemic quadriparesis. Neurol India. 2011 Jan-Feb;59(1):143. doi: 10.4103/0028-3886.76887. PMID: 21339693.

Chronic subdural hematoma treatment

Chronic subdural hematoma treatment

Corticosteroids are associated with reduced recurrence but also increased morbidity. Drains reduce the risk of recurrence, but the position of drain (subdural vs subgaleal) did not influence recurrence. Middle meningeal artery embolization is a promising treatment warranting further evaluation in randomized trials 1).

Surgical therapies involve the irrigation and removal of the blood products, sometimes with partial resection of these vascular membranes 2).

Investigational medical therapies have employed various strategies, which include reducing the rate of microhemorrhage from the membranes, changing the osmotic environment, or altering angiogenesis 3).

Endovascular therapies are aimed at de-vascularizing these membranes 4) 5) 6) 7).

Providing a high level of evidence to propose a standard of care for this frequent pathology is of utmost importance. However, two surveys in the UK and in France have shown a wide range of practice, without major rationale 8) 9).

A variety of clinical factors must be taken into account in the treatment of chronic subdural hematoma (cSDH), and the multifaceted treatment paradigms continue to evolve 10).

There is lack of uniformity about the treatment strategies, such as the role of burr hole, twist drill, craniotomy, etc., in CSDH amongst various surgeons. There is also disagreement about the use of drain, irrigation, and steroid 11) 12).

Surgery is usually the treatment of choice, but conservative treatment may be a good alternative in some situations.

Chronic subdural hematoma surgery

see Chronic subdural hematoma surgery.

Middle Meningeal Artery Embolization

see Middle meningeal artery embolization for chronic subdural hematoma.

Systematic reviews

Chronic subdural hematoma recurrence after evacuation occurs in approximately 10% of chronic subdural hematomas, and the various Chronic subdural hematoma surgery interventions are approximately equivalent. Corticosteroids are associated with reduced recurrence but also increased morbidity. Drains reduce the risk of recurrence, but the position of drain (subdural vs subgaleal) did not influence recurrence. Middle meningeal artery embolization is a promising treatment warranting further evaluation in randomized trials 13).

Soleman et al., provide a systematic review of studies analysing the conservative treatment options and the natural history of cSDH. Of 231 articles screened, 35 were included in this systematic review. Studies evaluating the natural history and conservative treatment modalities of cSDH remain sparse and are predominantly of low level of evidence. The natural history of cSDH remains unclear and is analysed only in case reports or very small case series. “Wait and watch” or “wait and scan” management is indicated in patients with no or minor symptoms (Markwalder score 0-1). However, it seems that there are no clear clinical or radiological signs indicating whether the cSDH will resolve spontaneously or not (type C recommendation). In symptomatic patients who are not worsening or in a comatose state, oral steroid treatment might be an alternative to surgery (type C recommendation). Tranexamic acid proved effective in a small patient series (type C recommendation), but its risk of increasing thromboembolic events in patients treated with antithrombotic or anticoagulant medication is unclear. Angiotensin converting-enzyme inhibitors were evaluated only as adjuvant therapy to surgery, and their effect on the rate of recurrence remains debatable. Mannitol showed promising results in small retrospective series and might be a valid treatment modality (type C recommendation). However, the long treatment duration is a major drawback. Patients presenting without paresis can be treated with a platelet activating factor receptor antagonist (type C recommendation), since they seem to promote resolution of the haematoma, especially in patients with subdural hygromas or low-density haematomas on computed tomography. Lastly, atorvastatin seems to be a safe option for the conservative treatment of asymptomatic or mildly symptomatic cSDH patients (type C recommendation). In conclusion, the knowledge of the conservative treatment modalities for cSDH is sparse and based on small case series and low grade evidence. However, some treatment modalities seem promising even in symptomatic patients with large haematomas. Randomised controlled trials are currently underway, and will hopefully provide us with good evidence for or against the conservative treatment of cSDH 14).

Surveys

The aim of a study was to survey aspects of current practice in the UK and Ireland. A 1-page postal questionnaire addressing the treatment of primary (i.e. not recurrent) CSDH was sent to consultant SBNS members in March 2006. There were 112 responses from 215 questionnaires (52%). The preferred surgical technique was burr hole drainage (92%). Most surgeons prefer not to place a drain, with 27% never using one and 58% using drain only in one-quarter of cases or less. Only 11% of surgeons always place a drain, and only 30% place one in 75% of cases or more. The closed subdural-to-external drainage was most commonly used (91%) with closed subgaleal-to-external and subdural-to-peritoneal conduit used less often (3 and 4%, respectively). Only 5% of responders claimed to know the exact recurrence rate. The average perceived recurrence rate among the surgeons that never use drains and those who always use drains, was the same (both 11%). Most operations are performed by registrars (77%). Postoperative imaging is requested routinely by 32% of respondents and 57% of surgeons prescribe bed rest. Ninety four per cent surgeons employ conservative management in less than one-quarter of cases. Forty-two per cent of surgeons never prescribe steroids, 55% prescribe them to those managed conservatively. This survey demonstrates that there are diverse practices in the management of CSDH. This may be because of sufficiently persuasive evidence either does not exist or is not always taken into account. The current literature provides Class II and III evidence and there is a need for randomized studies to address the role of external drainage, steroids and postoperative bed rest 15).

Cenic et al. developed and administered a questionnaire to Canadian Neurosurgeons with questions relating to the management of chronic and subacute subdural hematoma. Our sampling frame included all neurosurgery members of the Canadian Neurosurgical Society.

Of 158 questionnaires, 120 were returned (response rate = 76%). The respondents were neurosurgeons with primarily adult clinical practices (108/120). Surgeons preferred one and two burr-hole craniostomy to craniotomy or twist-drill craniostomy as the procedure of choice for initial treatment of subdural hematoma (35.5% vs 49.5% vs 4.7% vs 9.3%, respectively). Craniotomy and two burr-holes were preferred for recurrent subdural hematomas (43.3% and 35.1%, respectively). Surgeons preferred irrigation of the subdural cavity (79.6%), use of a subdural drain (80.6%), and no use of anti-convulsants or corticosteroids (82.1% and 86.6%, respectively). We identified a lack of consensus with keeping patients supine following surgery and post-operative antibiotic use.

The survey has identified variations in practice patterns among Canadian Neurosurgeons with respect to treatment of subacute or chronic subdural hematoma (SDH). Our findings support the need for further prospective studies and clinical trials to resolve areas of discrepancies in clinical management and hence, standardize treatment regimens 16).

Steroids

Steroids for chronic subdural hematoma.

Goreisan

see Goreisan for chronic subdural hematoma

Chronic subdural hematoma seizure prophylaxis

see Chronic subdural hematoma seizure prophylaxis.

Anticoagulation resumption after chronic subdural hematoma

Anticoagulation resumption after chronic subdural hematoma.

References

1) , 13)

Henry J, Amoo M, Kissner M, Deane T, Zilani G, Crockett MT, Javadpour M. Management of Chronic Subdural Hematoma: A Systematic Review and Component Network Meta-analysis of 455 Studies With 103 645 Cases. Neurosurgery. 2022 Dec 1;91(6):842-855. doi: 10.1227/neu.0000000000002144. Epub 2022 Sep 28. PMID: 36170165.
2)

Markwalder TM . The course of chronic subdural hematomas after burr-hole craniostomy with and without closed-system drainage. Neurosurg Clin N Am 2000;11:541–6.doi:10.1016/S1042-3680(18)30120-7
3)

Sun TF , Boet R , Poon WS . Non-surgical primary treatment of chronic subdural haematoma: preliminary results of using dexamethasone. Br J Neurosurg 2005;19:327–33.doi:10.1080/02688690500305332
4)

Link TW , Boddu S , Marcus J , et al . Middle meningeal artery embolization as treatment for chronic subdural hematoma: a case series. Oper Neurosurg 2018;14:556–62.doi:10.1093/ons/opx154
5)

Link TW , Boddu S , Paine SM , et al . Middle meningeal artery embolization for chronic subdural hematoma: a series of 60 cases. Neurosurgery 2018;121.doi:10.1093/neuros/nyy521
6)

Link TW , Rapoport BI , Paine SM , et al . Middle meningeal artery embolization for chronic subdural hematoma: Endovascular technique and radiographic findings. Interv Neuroradiol 2018;24:455–62.doi:10.1177/1591019918769336
7)

Link TW , Schwarz JT , Paine SM , et al . Middle meningeal artery embolization for Chronic subdural hematoma recurrence: a case series. World Neurosurg 2018;118:e570–4.doi:10.1016/j.wneu.2018.06.241
8)

M. Guénot, Hématome sous-dural chronique. Introduction et résultats de l’enquête de la SFNC, Neurochirurgie 4 (2001) 459–460 https://doi.org/ NCHIR-11-2001-47- 5-0028-3770-101019-ART7.
9)

] T. Santarius, R. Lawton, P.J. Kirkpatrick, P.J. Hutchinson, The management of primary chronic subdural haematoma: a questionnaire survey of practice in the United Kingdom and the Republic of Ireland, Br. J. Neurosurg. 22 (2008) 529–534, https://doi.org/10.1080/02688690802195381.
10)

Sahyouni R, Goshtasbi K, Mahmoodi A, Tran DK, Chen JW. Chronic Subdural Hematoma: A Historical and Clinical Perspective. World Neurosurg. 2017 Dec;108:948-953. doi: 10.1016/j.wneu.2017.09.064. Epub 2017 Sep 19. Review. PubMed PMID: 28935548.
11) , 15)

Santarius T, Lawton R, Kirkpatrick PJ, Hutchinson PJ. The management of primary chronic subdural haematoma: a questionnaire survey of practice in the United Kingdom and the Republic of Ireland. Br J Neurosurg. 2008 Aug;22(4):529-34. doi: 10.1080/02688690802195381. PubMed PMID: 18686063.
12)

Cenic A, Bhandari M, Reddy K. Management of chronic subdural hematoma: a national survey and literature review. Can J Neurol Sci. 2005 Nov;32(4):501-6. PubMed PMID: 16408582.
14)

Soleman J, Noccera F, Mariani L. The conservative and pharmacological management of chronic subdural haematoma. Swiss Med Wkly. 2017 Jan 19;147:w14398. doi: smw.2017.14398. PubMed PMID: 28102879.
16)

Cenic A, Bhandari M, Reddy K. Management of chronic subdural hematoma: a national survey and literature review. Can J Neurol Sci. 2005 Nov;32(4):501-6. PubMed PMID: 16408582.

t

A variety of clinical factors must be taken into account in the treatment of chronic subdural hematoma (cSDH), and the multifaceted treatment paradigms continue to evolve 1).

There is lack of uniformity about the treatment strategies, such as the role of burr hole, twist drill, craniotomy, etc., in CSDH amongst various surgeons. There is also disagreement about the use of drain, irrigation, and steroid 2) 3).

Surgery is usually the treatment of choice, but conservative treatment may be a good alternative in some situations.

see DECSA trial.

see Middle Meningeal Artery Embolization.

Chronic subdural hematoma surgery

see Chronic subdural hematoma surgery.

Systematic reviews

Soleman et al., provide a systematic review of studies analysing the conservative treatment options and the natural history of cSDH. Of 231 articles screened, 35 were included in this systematic review. Studies evaluating the natural history and conservative treatment modalities of cSDH remain sparse and are predominantly of low level of evidence. The natural history of cSDH remains unclear and is analysed only in case reports or very small case series. “Wait and watch” or “wait and scan” management is indicated in patients with no or minor symptoms (Markwalder score 0-1). However, it seems that there are no clear clinical or radiological signs indicating whether the cSDH will resolve spontaneously or not (type C recommendation). In symptomatic patients who are not worsening or in a comatose state, oral steroid treatment might be an alternative to surgery (type C recommendation). Tranexamic acid proved effective in a small patient series (type C recommendation), but its risk of increasing thromboembolic events in patients treated with antithrombotic or anticoagulant medication is unclear. Angiotensin converting-enzyme inhibitors were evaluated only as adjuvant therapy to surgery, and their effect on the rate of recurrence remains debatable. Mannitol showed promising results in small retrospective series and might be a valid treatment modality (type C recommendation). However, the long treatment duration is a major drawback. Patients presenting without paresis can be treated with a platelet activating factor receptor antagonist (type C recommendation), since they seem to promote resolution of the haematoma, especially in patients with subdural hygromas or low-density haematomas on computed tomography. Lastly, atorvastatin seems to be a safe option for the conservative treatment of asymptomatic or mildly symptomatic cSDH patients (type C recommendation). In conclusion, the knowledge of the conservative treatment modalities for cSDH is sparse and based on small case series and low grade evidence. However, some treatment modalities seem promising even in symptomatic patients with large haematomas. Randomised controlled trials are currently underway, and will hopefully provide us with good evidence for or against the conservative treatment of cSDH 4).

Surveys

The aim of a study was to survey aspects of current practice in the UK and Ireland. A 1-page postal questionnaire addressing the treatment of primary (i.e. not recurrent) CSDH was sent to consultant SBNS members in March 2006. There were 112 responses from 215 questionnaires (52%). The preferred surgical technique was burr hole drainage (92%). Most surgeons prefer not to place a drain, with 27% never using one and 58% using drain only in one-quarter of cases or less. Only 11% of surgeons always place a drain, and only 30% place one in 75% of cases or more. The closed subdural-to-external drainage was most commonly used (91%) with closed subgaleal-to-external and subdural-to-peritoneal conduit used less often (3 and 4%, respectively). Only 5% of responders claimed to know the exact recurrence rate. The average perceived recurrence rate among the surgeons that never use drains and those who always use drains, was the same (both 11%). Most operations are performed by registrars (77%). Postoperative imaging is requested routinely by 32% of respondents and 57% of surgeons prescribe bed rest. Ninety four per cent surgeons employ conservative management in less than one-quarter of cases. Forty-two per cent of surgeons never prescribe steroids, 55% prescribe them to those managed conservatively. This survey demonstrates that there are diverse practices in the management of CSDH. This may be because of sufficiently persuasive evidence either does not exist or is not always taken into account. The current literature provides Class II and III evidence and there is a need for randomized studies to address the role of external drainage, steroids and postoperative bed rest 5).

Cenic et al. developed and administered a questionnaire to Canadian Neurosurgeons with questions relating to the management of chronic and subacute subdural hematoma. Our sampling frame included all neurosurgery members of the Canadian Neurosurgical Society.

Of 158 questionnaires, 120 were returned (response rate = 76%). The respondents were neurosurgeons with primarily adult clinical practices (108/120). Surgeons preferred one and two burr-hole craniostomy to craniotomy or twist-drill craniostomy as the procedure of choice for initial treatment of subdural hematoma (35.5% vs 49.5% vs 4.7% vs 9.3%, respectively). Craniotomy and two burr-holes were preferred for recurrent subdural hematomas (43.3% and 35.1%, respectively). Surgeons preferred irrigation of the subdural cavity (79.6%), use of a subdural drain (80.6%), and no use of anti-convulsants or corticosteroids (82.1% and 86.6%, respectively). We identified a lack of consensus with keeping patients supine following surgery and post-operative antibiotic use.

The survey has identified variations in practice patterns among Canadian Neurosurgeons with respect to treatment of subacute or chronic subdural hematoma (SDH). Our findings support the need for further prospective studies and clinical trials to resolve areas of discrepancies in clinical management and hence, standardize treatment regimens 6).

Glucocorticoids

Since glucocorticoids have been used for treatment of cSDH in 1962 their role is still discussed controversially in lack of evident data. On the basis of the ascertained inflammation cycle in cSDH dexamethasone will be an ideal substance for a short lasting, concomitant treatment protocol.

A study is designed as a double-blind randomized placebo-controlled trial 820 patients who are operated for cSDH and from the age of 25 years are included after obtaining informed consent. They are randomized for administration of dexamethasone (16-16-12-12-8-4 mg/d) or placebo (maltodextrin) during the first 48 hours after surgery. The type I error is 5% and the type II error is 20%. The primary endpoint is the reoperation within 12 weeks postoperative.

This study tests whether dexamethasone administered over 6 days is a safe and potent agent in relapse prevention for evacuated cSDH 7).

Chronic subdural hematoma seizure prophylaxis

see Chronic subdural hematoma seizure prophylaxis.

Anticoagulation resumption after chronic subdural hematoma

Anticoagulation resumption after chronic subdural hematoma.

References

1)

Sahyouni R, Goshtasbi K, Mahmoodi A, Tran DK, Chen JW. Chronic Subdural Hematoma: A Historical and Clinical Perspective. World Neurosurg. 2017 Dec;108:948-953. doi: 10.1016/j.wneu.2017.09.064. Epub 2017 Sep 19. Review. PubMed PMID: 28935548.
2) , 5)

Santarius T, Lawton R, Kirkpatrick PJ, Hutchinson PJ. The management of primary chronic subdural haematoma: a questionnaire survey of practice in the United Kingdom and the Republic of Ireland. Br J Neurosurg. 2008 Aug;22(4):529-34. doi: 10.1080/02688690802195381. PubMed PMID: 18686063.
3)

Cenic A, Bhandari M, Reddy K. Management of chronic subdural hematoma: a national survey and literature review. Can J Neurol Sci. 2005 Nov;32(4):501-6. PubMed PMID: 16408582.
4)

Soleman J, Noccera F, Mariani L. The conservative and pharmacological management of chronic subdural haematoma. Swiss Med Wkly. 2017 Jan 19;147:w14398. doi: smw.2017.14398. PubMed PMID: 28102879.
6)

Cenic A, Bhandari M, Reddy K. Management of chronic subdural hematoma: a national survey and literature review. Can J Neurol Sci. 2005 Nov;32(4):501-6. PubMed PMID: 16408582.
7)

Emich S, Richling B, McCoy MR, Al-Schameri RA, Ling F, Sun L, Wang Y, Hitzl W. The efficacy of dexamethasone on reduction in the reoperation rate of chronic subdural hematoma – the DRESH study: straightforward study protocol for a randomized controlled trial. Trials. 2014 Jan 6;15(1):6. doi: 10.1186/1745-6215-15-6. PubMed PMID: 24393328; PubMed Central PMCID: PMC3891985.

AO Spine Upper Cervical Injury Classification System

AO Spine Upper Cervical Injury Classification System

Latest AO Spine Upper Cervical Injury Classification System PubMed related Articles

see AO Spine Upper Cervical Injury Classification System

In the pediatric population. While moderate to substantial agreement was found, limitations to applying the Upper Cervical Injury Classification System to the pediatric population exist, and thus the UCCS can be considered a starting point for developing a pediatric classification 1)

Accuracy

Early phase validation demonstrated classification of upper cervical spine injuries using the AO Spine Upper Cervical Injury Classification System to be accurate, reliable, and reproducible. Greater than 80% accuracy was detected for injury classification. The intraobserver reproducibility was excellent, while the interobserver reliability was substantial 2)

The AO Spine Upper Cervical Injury Classification System can be applied with high accuracy, interobserver reliability, and intraobserver reproducibility. However, lower classification accuracy and reliability were found in regions of Africa and Central/South America, especially for severe atlas injuries (IIB and IIC) and atypical hangman’s type fractures (IIIB injuries) 3).

A study reported an acceptable reproducibility of the new AO UCCS and safety in recommending the treatment. Further clinical studies with a larger patient sample, multicenter and international, are necessary to sustain the universal and homogeneity quality of the new AO UCCS 4)

Type A

AO Spine Upper Cervical Injury Classification System Type A

I. Occipital Condyle and Craniocervical junction. Isolated bony injury (condyle) Isolated bony injury (condyle)

II. C1 Ring and C1-2 Joint. Isolated bony only (arch)

III. C2 and C2-3 Joint. Bony injury only without ligamentous, tension band, discal injury

Type B

Type B injuries are the most difficult injury type to correctly classify. They are classified with greater reliability and classification accuracy when evaluated by academic surgeons, hospital-employed surgeons, and surgeons associated with higher-level trauma centers (I or II/III) 5)

Atlas fracture

see also Atlas fracture classification

Axis fracture

see also Axis fracture classification,

AOSpine subaxial cervical spine injury classification system

AOSpine subaxial cervical spine injury classification system.

The AO classification according to Magerl et al. is used for the subaxial spine, whereas the upper cervical spine should be classified separately because the anatomy is different at each level 6)

1)

O’Neill NP, Mo AZ, Miller PE, Glotzbecker MP, Li Y, Fletcher ND, Upasani VV, Riccio AI, Spence D, Garg S, Krengel W, Birch C, Hedequist DJ. The Reliability of the AO Spine Upper Cervical Classification System in Children: Results of a Multi-Center Study. J Pediatr Orthop. 2023 Apr 1;43(4):273-277. doi: 10.1097/BPO.0000000000002363. Epub 2023 Jan 30. PMID: 36706430.
2)

Vaccaro AR, Lambrechts MJ, Karamian BA, Canseco JA, Oner C, Vialle E, Rajasekaran S, Dvorak MR, Benneker LM, Kandziora F, El-Sharkawi M, Tee JW, Bransford R, Joaquim AF, Muijs SPJ, Holas M, Takahata M, Hamouda WO, Kanna RM, Schnake K, Kepler CK, Schroeder GD. AO Spine upper cervical injury classification system: a description and reliability study. Spine J. 2022 Dec;22(12):2042-2049. doi: 10.1016/j.spinee.2022.08.005. Epub 2022 Aug 12. PMID: 35964830.
3)

Lambrechts MJ, Schroeder GD, Karamian BA, Canseco JA, Bransford R, Oner C, Benneker LM, Kandziora F, Shanmuganathan R, Kanna R, Joaquim AF, Chapman JR, Vialle E, El-Sharkawi M, Dvorak M, Schnake K, Kepler CK, Vaccaro AR; AO Spine Upper Cervical Injury Classification International Members. Global Validation of the AO Spine Upper Cervical Injury Classification: Geographic Region Affects Reliability and Reproducibility. Global Spine J. 2022 Aug 29:21925682221124100. doi: 10.1177/21925682221124100. Epub ahead of print. PMID: 36036763.
4)

Maeda FL, Formentin C, de Andrade EJ, Rodrigues PAS, Goyal DKC, Shroeder GD, Patel AA, Vaccaro AR, Joaquim AF. Reliability of the New AOSpine Classification System for Upper Cervical Traumatic Injuries. Neurosurgery. 2020 Mar 1;86(3):E263-E270. doi: 10.1093/neuros/nyz464. PMID: 31642504.
5)

Lambrechts MJ, Schroeder GD, Karamian BA, Canseco JA, Bransford R, Oner C, Benneker LM, Kandziora F, Shanmuganathan R, Kanna R, Joaquim AF, Chapman JR, Vialle E, El-Sharkawi M, Dvorak M, Schnake K, Kepler CK, Vaccaro AR. The AO spine upper cervical injury classification system: Do work setting or trauma center affiliation affect classification accuracy or reliability? Injury. 2022 Oct;53(10):3248-3254. doi: 10.1016/j.injury.2022.08.030. Epub 2022 Aug 15. PMID: 36038389.
6)

Rieger M, Mallouhi A, El-Attal R, Kathrein A, Knop C, Blauth M, Jaschke W. Akutdiagnostik des Wirbelsäulentraumas [Acute diagnosis of spinal trauma]. Radiologe. 2006 Jun;46(6):527-41; quiz 542-3. German. doi: 10.1007/s00117-006-1355-x. PMID: 16607557.