Spontaneous Intracerebral Hemorrhage Risk Factors

Spontaneous Intracerebral Hemorrhage Risk Factors

Psychosocial, ethnic, and economic factors play a role in the prevalence of cerebral hemorrhage, with ICH being twice as common in low-income and middle-income countries compared with high-income countries. Other identified risk factors for ICH include age (i.e., each decade from 50 years of age is associated with a 2-fold increase in the incidence of ICH) and an elevated alcohol intake.

Etiologies of ICH to always consider include intracranial aneurysms (typically presenting as subarachnoid hemorrhage); arteriovenous malformations (ICH is the first presentation of AVMs in 60 % of cases); cerebral venous sinus thrombosis and venous infarction; brain tumors (<5 % of all ICH cases) including cerebral metastases (e.g., lung cancer, melanoma, renal cell carcinoma, thyroid carcinoma, and choriocarcinoma) and primary CNS tumors (e.g., glioblastoma multiforme and oligodendrogliomas); and drugs of abuse (e.g., cocaine, amphetamines). Because of the differing etiologies of ICH, a rapid and accurate diagnosis of the underlying etiology of ICH is essential to direct appropriate management strategies.

The most important modifiable risk factor in spontaneous ICH is chronic arterial hypertension:

see Hypertensive intracerebral hemorrhage.

Besides hypertension, cerebrovascular amyloid deposition (i.e., cerebral amyloid angiopathy) is associated with ICH in older patients.


Although cerebral amyloid angiopathy (CAA), which is Aβ deposition in the cerebral vessels, related cerebral hemorrhage rarely develops in young people, several patients with CAA-related cerebral hemorrhage under the age of 55 with histories of neurosurgeries with and without dura mater graft in early childhood have been reported. These patients might show that Aβ pathology is often recognized as Aβ-CAA rather than parenchymal Aβ deposition in the transmission of cerebral β-amyloidosis in humans, and Hamaguchi et al. proposed an emerging concept, “acquired CAA”. Considering that there have been several patients with acquired CAA with an incubation period from neurosurgery and the onset of CAA-related cerebral hemorrhage of longer than 40 years, the number of cases is likely to increase in the future, and detailed epidemiological investigation is required. It is necessary to continue to elucidate the pathomechanisms of acquired CAA and urgently establish a method for preventing the transmission of cerebral β-amyloidosis among individuals 1).

It is a common initial symptom of intracranial vascular malformations.

see Intracerebral hemorrhage from ruptured cerebral arteriovenous malformation.

see Aneurysmal intracerebral hemorrhage.

see Cerebral venous sinus thrombosis and venous infarction.

see Spontaneous intracranial hematoma caused by neoplasm.

Vasculitis.

Complication of AIDS.

Shunting for NPH

Coagulopathies (i.e., the use of antithrombotic or thrombolytic agents, congenital or acquired factor deficiencies) and systemic diseases, such as thrombocytopenia, are possible causes of ICH. The use of oral anticoagulants, especially vitamin K inhibitors (i.e., warfarin), has increased coagulopathy-associated ICH in recent years, accounting for more than 15 % of all cases.

Severe thrombocytopenia can result in petechial hemorrhages or spontaneous intracerebral hemorrhage (ICH).

see Anticoagulant Related Intracerebral Hemorrhage.


Intracerebral hemorrhage risk is increased with higher doses than the recommended 100 mg of alteplase (Activase®, recombinant tissue plasminogen activator (rt-PA)) 2) in older patients, in those with anterior MI or higher Killip class, and with bolus administration (vs. infusion) 3).

When heparin was used adjunctively, higher doses were associated with a higher risk of ICH 4) ICH is thought to occur in those patients with some preexisting underlying vascular abnormality 5). Immediate coronary angioplasty is safer than rt-PA when available 6).

Remote supratentorial hematoma soon after posterior fossa surgery for the removal of a space-occupying lesion is a rare but dramatic and dreaded complication, carrying significant morbidity and mortality 7) 8) 9) 10) 11) 12) 13) 14).

see Posterior reversible encephalopathy syndrome.

Ethanol

Cocaine

Inadvertent intrathecal injection of unapproved contrast agents.

The evidence linking vitamin D (VitD) levels and Spontaneous Intracerebral Hemorrhage Risk Factors remains inconclusive. Szejko et al. tested the hypothesis that lower genetically determined VitD levels are associated with a higher risk of ICH. They conducted a 2-sample Mendelian Randomization (MR) study using publicly available summary statistics from published genome-wide association study of VitD levels (417 580 study participants) and ICH (1545 ICH cases and 1481 matched controls). They used the inverse variance-weighted average method to generate causal estimates and the MR Pleiotropy Residual Sum and Outlier and MR-Egger approaches to assess for horizontal pleiotropy. To account for known differences in their underlying mechanism, we implemented stratified analysis based on the location of the hemorrhage within the brain (lobar or nonlobar). Our primary analysis indicated that each SD decrease in genetically instrumented VitD levels was associated with a 60% increased risk of ICH (odds ratio [OR], 1.60; [95% CI, 1.05-2.43]; P=0.029). They found no evidence of horizontal pleiotropy (MR-Egger intercept and MR Pleiotropy Residual Sum and Outlier global test with P>0.05). Stratified analyses indicated that the association was stronger for nonlobar ICH (OR, 1.87; [95% CI, 1.18-2.97]; P=0.007) compared with lobar ICH (OR, 1.43; [95% CI, 0.86-2.38]; P=0.17). Lower levels of genetically proxied VitD levels are associated with higher ICH risk. These results provide evidence for a causal role of VitD metabolism in ICH 15).

COVID-19 and Intracerebral Hemorrhage


1)

Hamaguchi T, Ono K, Yamada M. Transmission of Cerebral β-Amyloidosis Among Individuals. Neurochem Res. 2022 Mar 11. doi: 10.1007/s11064-022-03566-4. Epub ahead of print. PMID: 35277809.
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Public Health Service. Approval of Thrombolytic Agents. FDA Drug Bull. 1988; 18:6–7
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Mehta SR, Eikelboom JW, Yusuf S. Risk of intracranial hemorrhage with bolus versus infusion thrombolytic therapy: a meta-analysis. Lancet. 2000; 356:449–454
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Tenecteplase (TNKase) for thrombolysis. Med Letter. 2000; 42:106–108
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DaSilva VF, Bormanis J. Intracerebral Hemorrhage After Combined Anticoagulant-Thrombolytic Therapy for Myocardial Infarction: Two Case Reports and a Short Review. Neurosurgery. 1992; 30:943–945
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Grines CL, Browne KF, Marco J, et al. A Comparison of Immediate Angioplasty with Thrombolytic Therapy for Acute Myocardial Infarction. N Engl J Med. 1993; 328:673–679
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Bucciero A, Quaglietta P, Vizioli L. Supratentorial intracerebral hemorrhage after posterior fossa surgery: Case report. J Neurosurg Sci. 1991;35:221–4.
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Haines SJ, Maroon JC, Jannetta PJ. Supratentorial intracerebral hemorrhage following posterior fossa surgery. J Neurosurg. 1978;49:881–6.
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Harders A, Gilsbach J, Weigel K. Supratentorial space occupying lesions following infratentorial surgery early diagnosis and treatment. Acta Neurochir (Wien) 1985;74:57–60.
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Seiler RW, Zurbrugg HR. Supratentorial intracerebral hemorrhage after posterior fossa operation. Neurosurgery. 1986;18:472–4.
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Tondon A, Mahapatra AK. Superatentorial intracerebral hemorrhage following infratentorial surgery. J Clin Neurosci. 2004;11:762–5.
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Vrettou CS, Stavrinou LC, Halikias S, Kyriakopoulou M, Kollias S, Stranjalis G, et al. Factor XIII deficiency as a potential cause of supratentorial haemorrhage after posterior fossa surgery. Acta Neurochir (Wien) 2010;152:529–32.
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Pandey P, Madhugiri VS, Sattur MG, Devi BI. Remote supratentorial extradural hematoma following posterior fossa surgery. Childs Nerv Syst. 2008;24:851–4.
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Wolfsberger S, Gruber A, Czech T. Multiple supratentorial epidural haematomas after posterior fossa surgery. Neurosurg Rev. 2004;27:128–32.
15)

Szejko N, Acosta JN, Both CP, Leasure A, Matouk C, Sansing L, Gill TM, Hongyu Z, Sheth K, Falcone GJ. Genetically-Proxied Levels of Vitamin D and Risk of Intracerebral Hemorrhage. J Am Heart Assoc. 2022 Jun 22:e024141. doi: 10.1161/JAHA.121.024141. Epub ahead of print. PMID: 35730641.

Ventriculostomy related infection risk factors

Ventriculostomy related infection risk factors

Ventriculostomy related infection risk factors include prior brain surgerycerebrospinal fluid fistula, and insertion site dehiscence. Walek et al. from Rhode Island Hospital found no significant association between infection risk and duration of external ventricular drainage placement 1).


A total of 15 supposed influencing factors includes: age, age & sex interactions, coinfection, catheter insertion outside the hospital, catheter type, CSF leakage, CSF sampling frequency, diagnosis, duration of catheterization, ICP > 20 mmHg, irrigation, multiple catheter, neurosurgical operation, reduced CSF glucose at catheter insertion and sex 2).


In a large series of patients, ventriculostomy related infection (VRI) was associated with a longer ICU stay, but its presence did not influence survival. A longer duration of ventriculostomy catheter monitoring in patients with VRI might be due to an increased volume of drained CSF during infection. Risk factors associated with VRIs are SAH, IVH, craniotomy, and coinfection 3).


A retrospective cohort study strengthens a growing body of works suggesting the importance of inoculation of skin flora as a critical risk factor in ventriculostomy related infections, underscoring the importance of drain changes only when clinically indicated and, that as soon as clinically permitted, catheters should be removed 4).


Associated with a longer ICU stay, but its presence did not influence survival. A longer duration of ventriculostomy catheter monitoring in patients with VAI might be due to an increased volume of drained CSF during infection. Risk factors associated with VAIs are subarachnoid hemorrhage (SAH), intraventricular hemorrhage IVH, craniotomy, and coinfection 5).

The risk of infection increases with increasing duration of catheterization and with repeated insertions. The use of local antibiotic irrigation or systemic antibiotics does not appear to reduce the risk of VAI. Routine surveillance cultures of CSF were no more likely to detect infection than cultures obtained when clinically indicated. These findings need to be considered in infection control policies addressing this important issue 6).


An increased risk of infection has been observed in patients with subarachnoid or intraventricular hemorrhage, in patients with concurrent systemic infections as well as with longer duration of catheterization, cerebrospinal (CSF) leakage, and frequent manipulation of the EVD system 7) 8) 9).

Many studies have been conducted to identify risk factors of EVD-related infections. However, none of these risk factors could be confirmed in a cohort of patients. Furthermore they not show any difference in infection rates between patients who were placed in single- or multibed rooms, respectively 10).


Interestingly no risk factor for EVD-related infection could be identified in a retrospective single center study 11).


1)

Walek KW, Leary OP, Sastry R, Asaad WF, Walsh JM, Horoho J, Mermel LA. Risk factors and outcomes associated with external ventricular drain infections. Infect Control Hosp Epidemiol. 2022 Apr 26:1-8. doi: 10.1017/ice.2022.23. Epub ahead of print. PMID: 35471129.
2)

Sorinola A, Buki A, Sandor J, Czeiter E. Risk Factors of External Ventricular Drain Infection: Proposing a Model for Future Studies. Front Neurol. 2019 Mar 15;10:226. doi: 10.3389/fneur.2019.00226. eCollection 2019. Review. PubMed PMID: 30930840; PubMed Central PMCID: PMC6428739.
3)

Bota DP, Lefranc F, Vilallobos HR, Brimioulle S, Vincent JL. Ventriculostomy-related infections in critically ill patients: a 6-year experience. J Neurosurg. 2005 Sep;103(3):468-72. PubMed PMID: 16235679.
4)

Katzir M, Lefkowitz JJ, Ben-Reuven D, Fuchs SJ, Hussein K, Sviri G. Decreasing external ventricular drain related infection rates with duration-independent, clinically indicated criteria for drain revision: A retrospective study. World Neurosurg. 2019 Aug 2. pii: S1878-8750(19)32121-7. doi: 10.1016/j.wneu.2019.07.205. [Epub ahead of print] PubMed PMID: 31382072.
5)

Bota DP, Lefranc F, Vilallobos HR, Brimioulle S, Vincent JL. Ventriculostomy-related infections in critically ill patients: a 6-year experience. J Neurosurg. 2005 Sep;103(3):468-72. PubMed PMID: 16235679.
6)

Arabi Y, Memish ZA, Balkhy HH, Francis C, Ferayan A, Al Shimemeri A, Almuneef MA. Ventriculostomy-associated infections: incidence and risk factors. Am J Infect Control. 2005 Apr;33(3):137-43. PubMed PMID: 15798667.
7)

Camacho E. F., Boszczowski Í., Basso M., Jeng B. C. P., Freire M. P., Guimarães T., Teixeira M. J., Costa S. F. Infection rate and risk factors associated with infections related to external ventricular drain. Infection. 2011;39(1):47–51. doi: 10.1007/s15010-010-0073-5.
8)

Kim J.-H., Desai N. S., Ricci J., Stieg P. E., Rosengart A. J., Hrtl R., Fraser J. F. Factors contributing to ventriculostomy infection. World Neurosurgery. 2012;77(1):135–140. doi: 10.1016/j.wneu.2011.04.017.
9)

Mayhall C. G., Archer N. H., Lamb V. A., Spadora A. C., Baggett J. W., Ward J. D., Narayan R. K. Ventriculostomy-related infections. A positive epidemiologic study. The New England Journal of Medicine. 1984;310(9):553–559. doi: 10.1056/NEJM198403013100903.
10)

Hagel S, Bruns T, Pletz MW, Engel C, Kalff R, Ewald C. External Ventricular Drain Infections: Risk Factors and Outcome. Interdiscip Perspect Infect Dis. 2014;2014:708531. Epub 2014 Nov 17. PubMed PMID: 25484896; PubMed Central PMCID: PMC4251652.
11)

Hagel S, Bruns T, Pletz MW, Engel C, Kalff R, Ewald C. External ventricular drain infections: risk factors and outcome. Interdiscip Perspect Infect Dis. 2014;2014:708531. doi: 10.1155/2014/708531. Epub 2014 Nov 17. PubMed PMID: 25484896; PubMed Central PMCID: PMC4251652.

Obstructive hydrocephalus from posterior fossa tumor risk factors

Obstructive hydrocephalus from posterior fossa tumor risk factors

Saad et al. from the Emory University Hospital surveyed the CNS (Central Nervous System) Tumor Outcomes Registry at Emory (CTORE) for patients who underwent posterior fossa tumor surgery at 3 tertiary-care centers between 2006 and 2019. Demographic, radiographic, perioperative, and dispositional data were analyzed using univariate and multivariate models.

They included 617 patients undergoing PFT resection for intra-axial (57%) or extra-axial (43%) lesions. Gross total resection was achieved in 62% of resections. Approximately 13% of patients required permanent cerebrospinal fluid shunt. Only 31.5% of patients who required pre- or intraop external ventricular drain (EVD) placement needed permanent cerebrospinal fluid shunt. On logistic regression, Tumor size, transependymal edema, use of perioperative external ventricular drain, postoperative intraventricular hemorrhage (IVH), and surgical complications were predictors of permanent CSF diversion. Preoperative tumor size was the only independent predictor of postoperative shunting in patients with subtotal resection. In patients with intra-axial tumors, transependymal flow (P = .014), postoperative IVH (P = .001), surgical complications (P = .013), and extent of resection (P = .03) predicted need for shunting. In extra-axial tumors, surgical complications were the major predictor (P = .022).

The study demonstrates that the presence of preoperative hydrocephalus in patients with PFT does not necessarily entail the need for permanent CSF diversion. Saad et al. reported the major predictive factors for needing a permanent cerebrospinal fluid shunt for obstructive hydrocephalus 1).


Superior tumor extension (into the aqueduct) and failed total resection of tumor were identified as independent risk factors for postoperative hydrocephalus in patients with fourth ventricle tumor 2).


Cully and colleagues analyzed 117 patients and found the following factors to be associated with a higher incidence of postresection hydrocephalus (PRH): age <3 years, midline tumor location, subtotal resection, prolonged EVD requirement, cadaveric dural grafts, pseudomeningocele formation, and CSF infections 3).

Due-Tonnessen and Hleseth found that patients with medulloblastoma and ependymoma had much higher rates of postoperative shunt placement than astrocytomas 4). Kumar and colleagues in a study of 196 consecutive children found age <3 years, tumor histology of medulloblastoma/ependymoma and partial resections were associated with the increased chances of postresection hydrocephalus 5). A study noted that the only modifiable risk factor for the development of PRH was the presence of intraventricular blood in postoperative imaging 6).

Intraventricular blood can cause hydrocephalus either by the “snow globe effect” 7) or by other factors like impaired absorption of CSF by inflammation and fibrosis of the arachnoid granulations caused by blood degradation products 8).

Gopalakrishnan and colleagues noted the following risk factors for PRH: the need for CSF diversion in the pediatric population—children with symptomatology <3 months duration, severe hydrocephalus at presentation, tumor location in the midline, tumor histology, viz. medulloblastoma and ependymoma, use of intraoperative EVD, longer duration of EVD, postoperative meningitis, and pseudomeningocele 9). Similar findings were also reported by Bognar et al. who showed that the presence of EVD and the duration of EVD were associated with a significant increase in the incidence of postresection CSF diversion. In another recent study, Pitsika et al. 10) showed that patients who underwent EVD had a higher rate of postoperative VPS. They also noted a negative correlation between early EVD clamping and VPS indicating that clamping encourages the re-establishment of normal CSF flow when the obstructive tumor is removed 11). From 12).


Choroid plexus cysts (CPCs) are a type of neuroepithelial cysts, benign lesions located more frequently in the supratentorial compartment. Symptomatic CPCs in the posterior fossa are extremely rare and can be associated with obstructive hydrocephalus

Predictive factors for postoperative hydrocephalus has been identified, including young age (< 3 years), severe symptomatic hydrocephalus at presentation, EVD placement before surgery, FOHR index > 0.46 and Evans index > 0.4, pseudomeningocelecerebrospinal fluid fistula, and infection. The use of a pre-resection cerebrospinal fluid shunt in case of signs and symptoms of hydrocephalus is mandatory, although it resolves in the majority of cases. As reported by several studies included in the present review, we suggest CSF shunt also in case of asymptomatic hydrocephalus, whereas it is not indicated without evidence of ventricular dilatation 13).


1)

Saad H, Bray DP, McMahon JT, Philbrick BD, Dawoud RA, Douglas JM, Adeagbo S, Yarmoska SK, Agam M, Chow J, Pradilla G, Olson JJ, Alawieh A, Hoang K. Permanent cerebrospinal fluid shunt in Adults With Posterior Fossa Tumors: Incidence and Predictors. Neurosurgery. 2021 Nov 18;89(6):987-996. doi: 10.1093/neuros/nyab341. PMID: 34561703; PMCID: PMC8600168.
2)

Chen T, Ren Y, Wang C, Huang B, Lan Z, Liu W, Ju Y, Hui X, Zhang Y. Risk factors for hydrocephalus following fourth ventricle tumor surgery: A retrospective analysis of 121 patients. PLoS One. 2020 Nov 17;15(11):e0241853. doi: 10.1371/journal.pone.0241853. PMID: 33201889; PMCID: PMC7671531.
3)

Cully DJ, Berger MS, Shaw D, Geyer R. An analysis of factors determing the need for ventriculoperitoneal shunts after posterior fossa tumor surgery in children. Neurosurgery 1994;34:402-8.
4) , 8)

Due-Tonnessen B, Helseth E. Management of hydrocephalus in children with posterior fossa tumors: Role of tumor surgery. Pediatr Neurosurg 2007;43:92-6
5)

Kumar V, Phipps K, Harkness W, Hayward RD. Ventriculoperitoneal shunt requirement in children with posterior fossa tumors: An 11-year audit. Br J Neurosurg 1996:10:467-70.
6)

Abraham A, Moorthy RK, Jeyaseelan L, Rajshekhar V. Postoperative intraventricular blood: A new modifiable risk factor for early postoperative symptomatic hydrocephalus in children with posterior fossa tumors. Childs Nerv Syst 2019;35;1137-46.
7)

Tamburrini G, Frassanito P, Bianchi F, Massimi L, Di Rocco C, Caldarelli M. Closure of endoscopic third ventriculostomy after surgery for posterior cranial fossa tumor: The “Snow Globe effect”. Br J Neurosurg 2015;29:386-9.
9)

Gopalakrishnan CV, Dhakoji A, Menon G, Nair S. Factors predicting the need for cerebrospinal fluid diversion following posterior cranial fossa tumor surgery in children. Pediatr Neurosurg 2012;48:93-101
10)

Pitsika M, Fletcher J, Coulter IC, Cowie CJA. A validation study of the modified Canadian preoperative prediction rule for hydrocephalus in children with posterior fossa tumors. J Neurosurg. doi: 10.3171/2021.1.PEDS20887.
11)

Bognar L, Borgulya G, Benke P, Madarassy G. Analysis of CSF shunting procedure requirement in children with posterior fossa tumors. Childs Nerv Syst 2003;19:332-6.
12)

Muthukumar N. Hydrocephalus Associated with Posterior Fossa Tumors: How to Manage Effectively? Neurol India. 2021 Nov-Dec;69(Supplement):S342-S349. doi: 10.4103/0028-3886.332260. PMID: 35102986.
13)

Anania P, Battaglini D, Balestrino A, D’Andrea A, Prior A, Ceraudo M, Rossi DC, Zona G, Fiaschi P. The role of external ventricular drainage for the management of posterior cranial fossa tumours: a systematic review. Neurosurg Rev. 2021 Jun;44(3):1243-1253. doi: 10.1007/s10143-020-01325-z. Epub 2020 Jun 3. PMID: 32494987.
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