Intracranial atherosclerosis

Intracranial atherosclerosis

see Large artery atherosclerosis

see Carotid artery atherosclerotic disease.

Intracranial atherosclerosis related large vessel occlusions (ICAS-O) are challenging to diagnose and manage. The degree of intracranial carotid artery calcification may assist pre-thrombectomy diagnosis of ICAS and guide treatment strategy.


The aim of a study was to report the relationship between cognitive function and risk factors at baseline and during follow-up in the Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis (SAMMPRIS) trial.

Subjects in the SAMMPRIS trial were included in this study. In order to have an assessment of cognitive function independent of stroke, patients with a stroke as a qualifying event whose deficits included aphasia or neglect were excluded from these analyses as were those with a cerebrovascular event during follow-up. The Montreal Cognitive Assessment (MoCA) score was used to assess cognitive impairment at baseline, 4 months, 12 months and closeout. Cognitive impairment was defined as MoCA < 26. A multivariate analysis was performed to determine what risk factors were independent predictors of cognitive function at baseline, 12 months and closeout. Among patients randomized to aggressive medical management only, the percentage of patients with cognitive impairment was compared between patients in versus out of target for each risk factor at 12 months and closeout.

Of the 451 patients in SAMMPRIS, 371 patients met the inclusion criteria. MoCA < 26 was present in 55% at baseline. Older age and physical inactivity were associated with cognitive impairment at baseline. Older age, non-white race, lower baseline body mass index, and baseline cognitive impairment were associated with cognitive impairment at 12 months. In the aggressive medical management group, at 12 months, physical inactivity during follow-up was the strongest risk factor associated with cognitive impairment.

Cognitive impairment is common in patients with severe symptomatic intracranial atherosclerosis. Physical inactivity at baseline and during follow-up is a strong predictor of cognitive impairment 1).


A study investigated whether inhalation of fine airborne particulate matters (PM2.5) causes ICA and whether omega-3 fatty acids (O3FA) attenuated the development of ICA.

Twelve but not 6 week exposure significantly increased triglycerides (TG) in normal chow diet (NCD), while PM2.5 enhanced all lipid profiles (TG, low density lipoprotein (LDL) and cholesterol (CHO)) after both 6 and 12-week exposure with high-cholesterol diet (HCD). PM2.5 exposure for 12 but not 6 weeks significantly induced middle cerebral artery (MCA) narrowing and thickening, in association with the enhanced expression of inflammatory cytokines, (interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), interferon gamma (IFN-γ)), vascular cell adhesion molecule 1 (VCAM-1) and inducible nitric oxide synthase (iNOS). O3FA significantly attenuated vascular alterations, even without favorable changes in lipid profiles, in association with reduced expression of IL-6, TNF-α, MCP-1, IFN-γ, VCAM-1 and iNOS in brain vessels.

PM2.5 exposure for 12 weeks aggravates ICA in a dietary model (HCD + short-term L-NAME), which may be mediated by vascular inflammation. O3FA dietary supplementation prevents ICA development and inflammatory reaction in cerebral vessels.

Adult Sprague-Dawly rats were under filtered air (FA) or PM2.5 exposure with NCD or HCD for 6 or 12 weeks. Half of the HCD rats were treated with O3FA (5 mg/kg/day) by gavage. A total of 600 mg NG-nitro-L-arginine methyl ester (L-NAME, 3 mg/mL) per rat was administered over two weeks as supplementation in the HCD group. Blood lipids, including LDL, CHO, TG and high density lipoprotein (HDL), were measured at 6 and 12 weeks. ICA was determined by lumen diameter and thickness of the MCA. Inflammatory markers, IL-6, TNF-α, MCP-1, IFN-γ, VCAM-1 and iNOS were assessed by real-time PCR for mRNA and Western blot for protein expression 2).

References

1)

Turan TN, Al Kasab S, Smock A, Cotsonis G, Bachman D, Lynn MJ, Nizam A, Derdeyn CP, Fiorella D, Janis S, Lane B, Montgomery J, Chimowitz MI; MBChB for the SAMMPRIS Investigators. Impact of Baseline Features and Risk Factor Control on Cognitive Function in the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis Trial. Cerebrovasc Dis. 2019 Feb 14;47(1-2):24-31. doi: 10.1159/000497245. [Epub ahead of print] PubMed PMID: 30763948.
2)

Guan L, Geng X, Shen J, Yip J, Li F, Du H, Ji Z, Ding Y. PM2.5 inhalation induces intracranial atherosclerosis which may be ameliorated by omega 3 fatty acids. Oncotarget. 2017 Dec 16;9(3):3765-3778. doi: 10.18632/oncotarget.23347. eCollection 2018 Jan 9. PubMed PMID: 29423081; PubMed Central PMCID: PMC5790498.

Intracranial epidermoid cyst

Intracranial epidermoid cyst

Epidemiology

Intracranial epidermoid cysts, are rare congenital lesions originating from the ectoderm that constitute 0.3 to 1.8 % of all intracranial neoplasms 1) 2).

The most common sites include

a) suprasellar: commonly produce bitemporal hemianopsia and optic atrophy, and only occasionally pituitary (endocrine) symptoms (including DI)

b) sylvian fissure: may present with seizures

c) cerebellopontine angle (CPA): may produce trigeminal neuralgia, especially in young patient

d) basilar-posterior fossa: may produce lower cranial nerve findings, cerebellar dysfunction, and/or corticospinal tract abnormalities

e) within the ventricular system: occur within the 4th ventricle more commonly than any other

Approximately half of these cysts are located at the cerebellopontine angle (CPA), although they can also be found in the parasellar regions, 4th ventricle, cerebellum, cerebral hemispheres, brainstem, and lateral ventricles.

see Cavernous sinus epidermoid

Cerebellopontine angle epidermoid cyst

Giant intracranial epidermoid.

Intradiploic epidermoid

Intraventricular epidermoid

Middle fossa epidermoid cyst

Pineal epidermoid cyst

Posterior fossa epidermoid cyst

Sylvian fissure epidermoid cyst.

Etiology

Intracranial epidermoid cysts, also known as primary cholesteatomas are considered to arise from epithelial inclusions at the time of neural tube closure or during formation of the secondary cerebral vesicles, and have slow growth rates resembling that of the normal epidermis 3).

Pathology

Pathologically, epidermoid cysts have well-circumscribed, irregular, thin walls with squamous epithelium lining. The epithelium undergoes progressive desquamation and keratin breakdown; therefore, the cystic contents include tissue debris, keratin, water, and solid cholesterol 4).

These tumors are congenital and arise from displaced epithelial tissue between the 3rd and 5th weeks of gestation, when neural tube closure occurs.

These brain lesions have an epithelial lining that encapsulates the tumor, which consists of desquamated epidermal cell debris. Most lesions are solid, but because the desquamated cells contain cholesterol some may have a liquid cystic center. The rate of tumor growth is gradual and linear, resembling the rate of human epidermis turnover, which is unlike the exponential growth of neoplastic lesions 5).

Diagnosis

Treatment

The treatment of choice for epidermoid cyst is a total resection of the tumor. But sometimes total resection is impossible because of anatomical complexity.

A conservative attitude in handling the tumor capsule is common given concerns about capsule adherence to neurovascular structures, and thus the possibility of recurrence is accepted with the intent of minimizing complications 6).

Outcome

Malignant transformation of an EC to squamous-cell carcinoma is rare; only 14 cases have been reported 7).

Case series

Vaz-Guimaraes et al., from Pittsburgh, Houston, and Toronto retrospectively reviewed the medical records of 21 patients who underwent endoscopic endonasal surgery for epidermoid and dermoid cyst resection at the University of Pittsburgh Medical Center between January 2005 and June 2014. Surgical outcomes and variables that might affect the extent of resection and complications were analyzed.

Total resection (total removal of cyst contents and capsule) was achieved in 8 patients (38.1%), near-total resection (total removal of cyst contents, incomplete removal of cyst capsule) in 9 patients (42.9%), and subtotal resection (incomplete removal of cyst contents and capsule) in 4 patients (19%). Larger cyst volume (≥ 3 cm3) and intradural location (15 cysts) were significantly associated with nontotal resection (p = 0.008 and 0.0005, respectively). In the whole series, surgical complications were seen in 6 patients (28.6%). No complications were observed in patients with extradural cysts. Among the 15 patients with intradural cysts, the most common surgical complication was postoperative CSF leak (5 patients, 33.3%), followed by postoperative intracranial infection (4 patients, 26.7%). Larger cysts and postoperative CSF leak were associated with intracranial infection (p = 0.012 and 0.028, respectively). Subtotal resection was marginally associated with intracranial infection when compared with total resection (p = 0.091). All patients with neurological symptoms improved postoperatively with the exception of 1 patient with unchanged abducens nerve palsy.

Endoscopic endonasal approaches may be effectively used for resection of epidermoid and dermoid cysts in carefully selected cases. These approaches are recommended for cases in which a total or near-total resection is possible in addition to a multilayer cranial base reconstruction with vascularized tissue to minimize the risk of intracranial infection 8).

References

1) , 3) , 4)

Kato K, Ujiie H, Higa T, Hayashi M, Kubo O, Okada Y, et al. Clinical presentation of intracranial epidermoids: a surgical series of 20 initial and four recurred cases. Asian J Neurosurg. 2010;5(1):32–40.
2)

Toglia JU, Netsky MG, Alexander E., Jr Epithelial (epidermoid) tumors of the cranium. Their common nature and pathogenesis. J Neurosurg. 1965;23(4):384–93. doi: 10.3171/jns.1965.23.4.0384.
5)

Alvord EC., Jr. Growth rates of epidermoid tumors. Ann Neurol. 1977;2:367–370.
6)

Aboud E, Abolfotoh M, Pravdenkova S, Gokoglu A, Gokden M, Al-Mefty O. Giant intracranial epidermoids: is total removal feasible? J Neurosurg. 2015 Jan 16:1-14. [Epub ahead of print] PubMed PMID: 25594324.
7)

Vellutini EA, de Oliveira MF, Ribeiro AP, Rotta JM. Malignant transformation of intracranial epidermoid cyst. Br J Neurosurg. 2014 Aug;28(4):507-9. doi: 10.3109/02688697.2013.869552. Epub 2013 Dec 18. Review. PubMed PMID: 24345076.
8)

Vaz-Guimaraes F, Koutourousiou M, de Almeida JR, Tyler-Kabara EC, Fernandez-Miranda JC, Wang EW, Snyderman CH, Gardner PA. Endoscopic endonasal surgery for epidermoid and dermoid cysts: a 10-year experience. J Neurosurg. 2018 Mar 1:1-11. doi: 10.3171/2017.7.JNS162783. [Epub ahead of print] PubMed PMID: 29547084.

EGFR Non small cell lung cancer intracranial metastases

EGFR Non small cell lung cancer intracranial metastases

Advances in our understanding of genomic alterations in lung cancer have led to the discovery of several driver mutations in non small cell lung cancer 1). The most common are the EGFR activating mutations, which are present in 50% of patients of Asian descent and in 10%–15% of white patients with NSCLC of adenocarcinoma histology 2).

Huang et al., investigated whether tumor mutation status (EGFRKRASALKROS1BRAF) and treatment history were associated with survivalafter neurosurgery.

They reviewed the electronic health records of 104 non small cell lung cancer (NSCLC) patients with genomic profiling who underwent neurosurgical resection for symptomatic brain metastases at an academic institution between January 2000 and January 2018.

They used multivariate Cox proportional hazards models to evaluate the association between overall survival (OS) after neurosurgery and clinico-pathological factors including mutation status.

Mean age of patients in this study was 61 (±12) years, and 44% were men. The median OS after neurosurgery was 24 months (95% confidence interval: 18-34). Our multivariate analysis showed that the presence of an EGFR mutation in the tumor was significantly associated with improved OS (hazard ratio [HR] 0.214 p = 0.029), independent of tyrosine kinase inhibitor (TKI) use. Presence of KRAS, ALK, ROS1 and BRAF alterations were not associated with survival (all p > 0.05). Conversely, older age (HR: 1.039; p=0.029), a history of multiple brain irradiation procedures (HR 9.197; p < 0.001) and presence of extracranial metastasis (HR 2.556; p = 0.016) resulted in increased risk of mortality.

Patients requiring surgical resection of an EGFR mutated NSCLC brain metastasis had an associated improved survival compared to patients without this mutation, independent of TKI use. Decreased survival was associated with older age, multiple prior brain radiation therapies and extracranial metastasis 3).


Activating mutations in the epidermal growth factor receptor (EGFR) predict for prolonged progression-free survival in patients with advanced non-small cell lung cancer (NSCLC) treated with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) versus chemotherapy.


A group of patients with non-small cell lung cancer (NSCLC) have tumors that contain an inversion in chromosome 2 that juxtaposes the 5′ end of the echinoderm microtubule-associated protein-like 4 (EML4) gene with the 3′ end of the anaplastic lymphoma kinase (ALK) gene, resulting in the novel fusion oncogene EML4-ALK


Multi-institutional analysis demonstrated that the use of upfront EGFR-TKI, and deferral of radiotherapy, is associated with inferior OS in patients with EGFR-mutant NSCLC who develop brain metastases. SRS followed by EGFR-TKI resulted in the longest OS and allowed patients to avoid the potential neurocognitive sequelae of WBRT. A prospective, multi-institutional randomized trial of SRS followed by EGFR-TKI versus EGFR-TKI followed by SRS at intracranial progression is urgently needed 4).

References

1)

Zer A, Leighl N. Promising targets and current clinical trials in metastatic non-squamous nsclc. Front Oncol. 2014;4:329. doi: 10.3389/fonc.2014.00329.
2)

Chan BA, Hughes BG. Targeted therapy for non-small cell lung cancer: current standards and the promise of the future. Transl Lung Cancer Res. 2015;4:36–54.
3)

Huang Y, Chow KKH, Aredo JV, Padda SK, Han SS, Kakusa BW, Gephart MH. EGFR mutation status confers survival benefit in non-small cell lung cancer patients undergoing surgical resection of brain metastases: a retrospective cohort study. World Neurosurg. 2019 Jan 30. pii: S1878-8750(19)30210-4. doi: 10.1016/j.wneu.2019.01.112. [Epub ahead of print] PubMed PMID: 30710723.
4)

Magnuson WJ, Lester-Coll NH, Wu AJ, Yang TJ, Lockney NA, Gerber NK, Beal K, Amini A, Patil T, Kavanagh BD, Camidge DR, Braunstein SE, Boreta LC, Balasubramanian SK, Ahluwalia MS, Rana NG, Attia A, Gettinger SN, Contessa JN, Yu JB, Chiang VL. Management of Brain Metastases in Tyrosine Kinase Inhibitor-Naïve Epidermal Growth Factor Receptor-Mutant Non-Small-Cell Lung Cancer: A Retrospective Multi-Institutional Analysis. J Clin Oncol. 2017 Apr 1;35(10):1070-1077. doi: 10.1200/JCO.2016.69.7144. Epub 2017 Jan 23. PubMed PMID: 28113019.
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