Chronic Cerebral Ischemia Treatment

Chronic Cerebral Ischemia Treatment

see also Acute Ischemic Stroke Treatment.


Carotid artery stenting

Revascularization for Chronic Cerebral Ischemia Treatment.

The role of cellular transplantation to promote functional recovery after stroke has been evaluated over the last two decades. Preclinical studies first established the potential for cultured neuronal cells derived from a teratocarcinoma cell line to be tested for safety and efficacy in the treatment of human stroke. In animal models of stroke that caused reproducible learning and motor deficits, injection of neuronal cells resulted in a return of learning behavior, retention time, and motor function. Clinical trials followed. Additional work with cells derived from a bone marrow neuroprogenitor line, fetal cortical stem cells, and other cell sources showed promise in preclinical studies and then these cells were tested in clinical studies 1).

prospective randomized trial (NCT03745092) enrolled 50 cases of CCI patients, which were divided into NBO (8 L/min of oxygen supplement) group and control group (room air) randomly, and also enrolled 21 healthy volunteers. Two times of 30-min EEG recordings with the interval of 45min of NBO or room air were analyzed quantitatively.

The CCI-mediated EEG presented with two patterns of electrical activities: high-power oscillations (high-power EEG, n = 26) and paroxysmal slow activities under the normal-power background (normal-power EEG, n = 24). The fronto-central absolute power (AP) of the beta, alpha, theta, and delta in the high-power EEG was higher than that in healthy EEG (p < 0.05). The fronto-central theta/alpha, delta/alpha and (delta + theta)/(alpha + beta) ratios in the normal-power EEG were higher than those in healthy EEG (p < 0.05). The high-power EEG in NBO group had higher fronto-central AP reduction rates than those in control group (p < 0.05). NBO remarkably reduced the fronto-central theta/alpha, delta/alpha, and (delta + theta)/(alpha + beta) ratios in the normal-power EEG (p < 0.05).

NBO rapidly ameliorates CCI-mediated EEG anomalies, including attenuation of the abnormal high-power oscillations and the paroxysmal slow activities associated with CCI 2).


1)

Kondziolka D. Stem Cell Treatment for Ischemic Stroke Recovery. Semin Neurol. 2021 Jan 27. doi: 10.1055/s-0040-1722640. Epub ahead of print. PMID: 33506475.
2)

Ding JY, Liu Y, Rajah GB, Chen ZY, Zhang SY, Ding YC, Ji XM, Meng R. Normobaric oxygen may correct chronic cerebral ischemia-mediated EEG anomalies. CNS Neurosci Ther. 2021 Jul 9. doi: 10.1111/cns.13703. Epub ahead of print. PMID: 34242498.

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.

Cerebral cavernous malformation treatment

Cerebral cavernous malformation treatment

Ren et al. demonstrated that cerebral cavernous malformation (CCM) growth requires increased PI3K/AKT/mTOR pathway and loss of CCM protein function. They identified PIK3CA gain of function (GOF) and CCM loss of function (LOF) somatic mutations in the same cells in a majority of human CCMs. Using mouse models, they showed that CCM growth requires both PI3K GOF and CCM LOF in endothelial cells, and that both CCM LOF and increased expression of the transcription factor KLF4, a downstream MEKK3 effector, augment mTOR signalling in endothelial cells. Consistent with these findings, the mTORC1 inhibitor Rapamycin effectively blocks CCM formation in mouse models. They established a three-hit mechanism analogous to cancer in which aggressive vascular malformations arise through the loss of vascular “suppressor genes” that constrain vessel growth and gain of a vascular “oncogene” that stimulates excess vessel growth. These findings suggest that aggressive CCMs may be treated using clinically approved mTORC1 inhibitors 1).

see Intracranial cavernous malformation surgery.


There have been few comparative studys of microsurgical excision vs conservative treatment of cerebral cavernous malformations (CCM) and none of them has reliably demonstrated a statistically and clinically significant difference.

A prospective, population-based study to identify and independently validate definite cerebral cavernous malformation diagnoses first made in 1999-2003 in Scottish adult residents, used multiple sources of prospective follow-up to assess adults’ dependence and to identify and independently validate outcome events.

Moultrie et al., used univariate and multivariable survival analyses to test the influence of CCM excision on outcome, adjusted for prognostic factors and baseline imbalances.

Of 134 adults, 25 underwent CCM excision; these adults were younger (34 vs 43 years at diagnosis, p = 0.004) and more likely to present with symptomatic intracranial hemorrhage or focal neurological deficit than adults managed conservatively (48% vs 26%; odds ratio 2.7, 95% confidence interval [CI] 1.1-6.5). During 5 years of follow-up, CCM excision was associated with a deterioration to an Oxford Handicap Scale score 2-6 sustained over at least 2 successive years (adjusted hazard ratio [HR] 2.2, 95% CI 1.1-4.3) and the occurrence of symptomatic intracranial hemorrhage or new focal neurologic deficit (adjusted HR 3.6, 95% CI 1.3-10.0).

CCM excision was associated with worse outcomes over 5 years compared to conservative management. Long-term follow-up will determine whether this difference is sustained over patients’ lifetimes. Meanwhile, a randomized controlled trial appears justified.

CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that CCM excision worsens short-term disability scores and increases the risk of symptomatic intracranial hemorrhage and new focal neurologic deficits 2).


Antithrombotic therapy use is associated with a lower risk of intracranial haemorrhage or focal neurological deficit from cerebral cavernous malformations than avoidance of antithrombotic therapy. These findings provide reassurance about safety for clinical practice and require further investigation in a randomised controlled trial 3).


1)

Ren AA, Snellings DA, Su YS, Hong CC, Castro M, Tang AT, Detter MR, Hobson N, Girard R, Romanos S, Lightle R, Moore T, Shenkar R, Benavides C, Beaman MM, Mueller-Fielitz H, Chen M, Mericko P, Yang J, Sung DC, Lawton MT, Ruppert M, Schwaninger M, Körbelin J, Potente M, Awad IA, Marchuk DA, Kahn ML. PIK3CA and CCM mutations fuel cavernomas through a cancer-like mechanism. Nature. 2021 Apr 28. doi: 10.1038/s41586-021-03562-8. Epub ahead of print. PMID: 33910229.
2)

Moultrie F, Horne MA, Josephson CB, Hall JM, Counsell CE, Bhattacharya JJ, Papanastassiou V, Sellar RJ, Warlow CP, Murray GD, Al-Shahi Salman R; Scottish Audit of Intracranial Vascular Malformations (SAIVMs) steering committee and collaborators. Outcome after surgical or conservative management of cerebral cavernous malformations. Neurology. 2014 Aug 12;83(7):582-9. doi: 10.1212/WNL.0000000000000684. Epub 2014 Jul 3. PubMed PMID: 24994841.
3)

Zuurbier SM, Hickman CR, Tolias CS, Rinkel LA, Leyrer R, Flemming KD, Bervini D, Lanzino G, Wityk RJ, Schneble HM, Sure U, Al-Shahi Salman R; Scottish Audit of Intracranial Vascular Malformations Steering Committee. Long-term antithrombotic therapy and risk of intracranial haemorrhage from cerebral cavernous malformations: a population-based cohort study, systematic review, and meta-analysis. Lancet Neurol. 2019 Aug 6. pii: S1474-4422(19)30231-5. doi: 10.1016/S1474-4422(19)30231-5. [Epub ahead of print] PubMed PMID: 31401075.
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