Malignant middle cerebral artery territory infarction

Malignant middle cerebral artery territory infarction

The malignant middle cerebral artery territory infarction is a distinct syndrome that occurs in up to 10% of stroke patients, 1) 2) which carries a mortality of up to 80% (mostly due to severe postischemic cerebral edema → increased ICP → herniation 3)

Patients usually present with findings of severe hemispheric stroke (hemiplegia, forced eye and head deviation) often with CT findings of major infarct within the first 12 hours. Most develop drowsiness shortly after admission. There is progressive deterioration during the first 2 days, and subsequent transtentorial herniation usually within 2–4 days of stroke. Fatalities are often associated with: severe drowsiness, dense hemiplegia, age > 45–50 yrs, 4) early parenchymal hypodensity involving > 50% of the MCA distribution on CT scan,23 midline shift > 8–10 mm, early sulci effacement, and hyperdense artery sign (p. 1354) 5) in MCA. Neurosurgeons may become involved in caring for these patients because aggressive therapies in these patients may reduce morbidity and mortality. Options include:

  1. conventional measures to control ICP (with or without ICP monitor): mortality is still high in this group and elevated ICP is not a common cause of initial neurologic deterioration in large hemispheric stroke

2. hemicraniectomy (decompressive craniectomy):

  1. ✖ to date, the following treatments have not improved outcome: agents to lyse clot, hyperventilationmannitol, or barbiturate coma.

In patients with severe middle cerebral artery (MCA), intracranial atherosclerotic disease (ICAD), the mechanism of stroke is multifactorial, but hemodynamic insufficiency plays a significant role. This finding is important in selecting a subgroup of patients who may benefit from revascularization 6).

see Malignant middle cerebral artery syndrome.

Malignant middle cerebral artery territory infarction diagnosis.

Malignant middle cerebral artery territory infarction treatment.

Malignant middle cerebral artery territory infarction outcome.

A case of a child with serological evidence of SARS-CoV-2 infection whose onset was a massive right cerebral artery ischemia that led to a malignant cerebral infarction. The patient underwent a life-saving decompressive hemicraniectomy, with good functional recovery, except for residual hemiplegia. During rehabilitation, the patient also developed a lower extremity peripheral nerve neuropathy, likely related to a long-Covid syndrome 7).


A 39-year-old woman in the 24th week of pregnancy who suffered a right malignant MCA infarction that eventually required DC. The patient delivered a healthy baby and underwent a second surgery for cranioplasty 7 months later. 8).


1)

Moulin DE, Lo R, Chiang J, et al. Prognosis in Middle Cerebral Artery Occlusion. Stroke. 1985;16:282–284
2) , 3)

Hacke W, Schwab S, Horn M, et al. Malignant Middle Cerebral Artery Territory Infarction: Clinical Course and Prognostic Signs. Arch Neurol. 1996; 53:309–315
4) , 5)

Wijdicks EFM, Diringer MN. Middle Cerebral Artery Territory Infarction and Early Brain Swelling: Progression and Effect of Age on Outcome. Mayo Clin Proc. 1998; 73:829–836
6)

Dubow JS, Salamon E, Greenberg E, Patsalides A. Mechanism of Acute Ischemic Stroke in Patients with Severe Middle Cerebral Artery Atherosclerotic Disease. J Stroke Cerebrovasc Dis. 2014 Jan 11. pii: S1052-3057(13)00425-4. doi: 10.1016/j.jstrokecerebrovasdis.2013.10.015. [Epub ahead of print] PubMed PMID: 24424333.
7)

Scala MR, Spennato P, Cicala D, Piccolo V, Varone A, Cinalli G. Malignant cerebral infarction associated with COVID-19 in a child. Childs Nerv Syst. 2021 Jun 26. doi: 10.1007/s00381-021-05273-x. Epub ahead of print. PMID: 34175976.
8)

Fernández García A, Jiménez Zapata HD, de Lera Alfonso MC, Sánchez Fernández C, Jiménez Arribas P, Rodríguez Arias CA. Decompressive Craniectomy in Pregnant Women. J Neurol Surg A Cent Eur Neurosurg. 2021 Jun 2. doi: 10.1055/s-0041-1726108. Epub ahead of print. PMID: 34077979.

Interstitial photodynamic therapy with 5-aminolevulinic acid for malignant brain tumor

Interstitial photodynamic therapy with 5-aminolevulinic acid for malignant brain tumor

Photodynamic therapy (PDT) remains a promising therapeutic approach that requires further study in high grade gliomas. Use of 5-ALA PDT permits selective tumor targeting due to the intracellular metabolism of 5-ALA. The immunomodulatory effects of PDT further strengthen its use for treatment of HGGs and requires a better understanding. The combination of PDT with adjuvant therapies for HGGs will need to be studied in randomized, controlled studies 1). 2).

PDT might be feasible for eliminating brain tumor cells in malignant pediatric brain tumors 3)


Computer simulation of the photophysical process in ALA-iPDT can offer a quantitative tool for understanding treatment outcomes, which depend on various variables related to clinical treatment conditions. Izumoto et al. proposed a clinical simulation method of ALA-iPDT for malignant brain tumors using a singlet oxygen (O12) model and O12 threshold to induce cell death. In this method, the amount of O12 generated is calculated using a photosensitizer photobleaching coefficient and O12 quantum yield, which have been measured in several previous studies. Results of the simulation using clinical magnetic resonance imaging data show the need to specify the insertion positions of cylindrical light diffusers and the level of light fluence. Detailed analysis with a numerical brain tumor model demonstrates that ALA-iPDT treatment outcomes depend on combinations of photobleaching and threshold values. These results indicate that individual medical procedures, including pretreatment planning and treatment monitoring, will greatly benefit from simulation of ALA-iPDT outcomes 4).


Glioma stem cells (GSLCs) expressed higher mRNA levels of protoporphyrin IX (PpIX) biosynthesis enzymes and its transporters PEPT1/2 and ABCB6, when compared to the parental A172 glioma cells. Consistently, flow cytometry analysis revealed that upon incubation with ALA, GSLCs accumulate a higher level of PpIX. Finally, Fujishiro et al., from the Department of Neurosurgery, Osaka Medical College, Takatsuki, Japan showed that GSLCs were more sensitive to 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) than the original A172 cells, and confirmed that all patient-derived glioma sphere lines also showed significantly increased sensitivity to ALA-PDT if cultivated under the pro-stem cell condition. This data indicate that ALA-PDT has potential as a novel clinically useful treatment that might eliminate GBM stem cells that are highly resistant to the current chemo- and radio-therapy 5).

References

1)

Mahmoudi K, Garvey KL, Bouras A, Cramer G, Stepp H, Jesu Raj JG, Bozec D, Busch TM, Hadjipanayis CG. 5-aminolevulinic acid photodynamic therapy for the treatment of high-grade gliomas. J Neurooncol. 2019 Feb;141(3):595-607. doi: 10.1007/s11060-019-03103-4. Epub 2019 Jan 18. Review. PubMed PMID: 30659522; PubMed Central PMCID: PMC6538286.
2)

Beck TJ, Kreth FW, Beyer W, Mehrkens JH, Obermeier A, Stepp H, Stummer W, Baumgartner R. Interstitial photodynamic therapy of nonresectable malignant glioma recurrences using 5-aminolevulinic acid induced protoporphyrin IX. Lasers Surg Med. 2007 Jun;39(5):386-93. PubMed PMID: 17565715.
3)

Schwake M, Nemes A, Dondrop J, Schroeteler J, Schipmann S, Senner V, Stummer W, Ewelt C. In-Vitro Use of 5-ALA for Photodynamic Therapy in Pediatric Brain Tumors. Neurosurgery. 2018 Dec 1;83(6):1328-1337. doi: 10.1093/neuros/nyy054. PubMed PMID: 29538709.
4)

Izumoto A, Nishimura T, Hazama H, Ikeda N, Kajimoto Y, Awazu K. Singlet oxygen model evaluation of interstitial photodynamic therapy with 5-aminolevulinic acid for malignant brain tumor. J Biomed Opt. 2019 Dec;25(6):1-13. doi: 10.1117/1.JBO.25.6.063803. PubMed PMID: 31838789.
5)

Fujishiro T, Nonoguchi N, Pavliukov M, Ohmura N, Park Y, Kajimoto Y, Ishikawa T, Nakano I, Kuroiwa T. 5-aminolevulinic acid-mediated photodynamic therapy can target human glioma stem-like cells refractory to antineoplastic agents. Photodiagnosis Photodyn Ther. 2018 Jul 7. pii: S1572-1000(18)30185-6. doi: 10.1016/j.pdpdt.2018.07.004. [Epub ahead of print] PubMed PMID: 29990642.

Malignant middle cerebral artery infarction outcome

Malignant middle cerebral artery infarction outcome

Malignant middle cerebral artery infarction is associated with high mortality and morbidity.

The mortality rate of patients with brain edema after malignant middle cerebral artery (MCA) infarction approaches 80 % without surgical intervention 1).

Over the past 10 years in Francedecompressive craniectomy (DC) has been increasingly performed for malignant middle cerebral artery infarction (MCI) regardless of age. However, in-hospital mortality remains considerable, as about one-quarter of patients died within the first weeks. For those who survive beyond 6 months, the risk of death significantly decreases. Early mortality is especially high for comatose patients above 60 years operated in inexperienced centers. Most of those who remain in good functional status tend to undergo a cranioplasty within the year following DC 2).


Three separate studies investigated the effectiveness of decompressive craniectomy after malignant MCA infarction in controlled trials with patients less than 61 years of age 3) 4) 5). These were demonstrated that hemicraniectomy reduced the mortality rate by 49% at one year after stroke when compared with conventional medical treatments. However, the question of how applicable the results are to patients older than 60 years of age still remains unanswered.

When neurosurgeons recommend decompressive surgery for patients with malignant infarcts, patients’ relatives often refuse the operation because of the patients’ age, past medical history or comorbidity. Such a situation occurs more frequently when the patient is older than 70 years of age 6).

References

1)

Huttner HB, Schwab S. Malignant middle cerebral artery infarction: clinical characteristics, treatment strategies, and future perspectives. Lancet Neurol 2009; 8:949–958.
2)

Champeaux C, Weller J. Long-Term Survival After Decompressive Craniectomy for Malignant Brain Infarction: A 10-Year Nationwide Study. Neurocrit Care. 2019 Jul 9. doi: 10.1007/s12028-019-00774-9. [Epub ahead of print] PubMed PMID: 31290068.
3)

Hofmeijer J, Kappelle LJ, Algra A, Amelink GJ, van Gijn J, van der Worp HB, et al. Surgical decompression for space-occupying cerebral infarction (the Hemicraniectomy After Middle Cerebral Artery infarction with Life-threatening Edema Trial [HAMLET]): a multicentre, open, randomised trial. Lancet Neurol. 2009 Apr;8(4):326–333.
4)

Jüttler E, Schwab S, Schmiedek P, Unterberg A, Hennerici M, Woitzik J, et al. Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery (DESTINY): a randomized, controlled trial. Stroke. 2007 Sep;38(9):2518–2525.
5)

Vahedi K, Vicaut E, Mateo J, Kurtz A, Orabi M, Guichard JP, et al. Sequential-design, multicenter, randomized, controlled trial of early decompressive craniectomy in malignant middle cerebral artery infarction (DECIMAL Trial) Stroke. 2007 Sep;38(9):2506–2517.
6)

Yu JW, Choi JH, Kim DH, Cha JK, Huh JT. Outcome following decompressive craniectomy for malignant middle cerebral artery infarction in patients older than 70 years old. J Cerebrovasc Endovasc Neurosurg. 2012 Jun;14(2):65-74. doi: 10.7461/jcen.2012.14.2.65. Epub 2012 Jun 30. PubMed PMID: 23210030; PubMed Central PMCID: PMC3471258.
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