Delayed cerebral ischemia treatment

Delayed cerebral ischemia treatment

Should We Focus on Blood Pressure or Vasodilatation1)


Rescue treatment for delayed cerebral ischemia (DCI) after subarachnoid hemorrhage can include induced hypertension (iHTN) and, in refractory cases, endovascular approaches, of which selective, continuous intraarterial nimodipine (IAN) is one variant. The combination of iHTN and IAN can dramatically increase vasopressor demand. In case of unsustainable doses, iHTN is often prioritized over IAN. However, evidence in this regard is largely lacking 2)


Level 1 rescue therapy consists of cardiac output optimization, hemoglobin optimization, and endovascular intervention, including angioplasty and intra-arterial vasodilator infusion. In highly refractory cases, level 2 rescue therapies are also considered, none of which have been validated 3).


To date, the only drug shown to be efficacious on both the incidence of vasospasm and poor outcome is nimodipine. Given its modest effects, new pharmacological treatments are being developed to prevent and treat DCI 4)

Volume expansion and hypertension are widely used for the hemodynamic management of patients with subarachnoid hemorrhage to prevent delayed cerebral ischemia.

For small, unruptured, unprotected intracranial aneurysms in SAH patients, the frequency of aneurysm rupture during vasopressor-induced hypertension (VIH) therapy is rare. Reynolds et al. do not recommend withholding VIH therapy from these patients 5).

A randomized pilot trial using a 2-way factorial design allocating patients within 72 hours of subarachnoid hemorrhage to either normovolemia (NV) or volume expansion (HV) and simultaneously to conventional (CBP) or augmented blood pressure (ABP) for 10 days. The study endpoints were protocol adherence and retention to follow-up. The quality of endpoints for a larger trial were 6-month modified Rankin Scale score, comprehensive neurobehavioral assessment, delayed cerebral ischemia, new stroke, and discharge disposition.

This pilot study showed adequate feasibility and excellent retention to follow-up. Given the suggestion of possible worse neurobehavioral outcome with ABP, a larger trial to determine the optimal blood pressure management in this patient population is warranted. (ClinTrials.gov NCT01414894.) 6).

see Delayed cerebral ischemia prevention.


1)

Sadan O, Akbik F. Treating Delayed Cerebral Ischemia: Should We Focus on Blood Pressure or Vasodilatation? Stroke. 2022 Jun 8:101161STROKEAHA122039800. doi: 10.1161/STROKEAHA.122.039800. Epub ahead of print. PMID: 35674047.
2)

Weiss M, Albanna W, Conzen-Dilger C, Kastenholz N, Seyfried K, Ridwan H, Wiesmann M, Veldeman M, Schmidt TP, Megjhani M, Schulze-Steinen H, Clusmann H, Aries MJH, Park S, Schubert GA. Intraarterial Nimodipine Versus Induced Hypertension for Delayed Cerebral Ischemia: A Modified Treatment Protocol. Stroke. 2022 Jun 8:101161STROKEAHA121038216. doi: 10.1161/STROKEAHA.121.038216. Epub ahead of print. PMID: 35674046.
3)

Francoeur CL, Mayer SA. Management of delayed cerebral ischemia after subarachnoid hemorrhage. Crit Care. 2016 Oct 14;20(1):277. doi: 10.1186/s13054-016-1447-6. PMID: 27737684; PMCID: PMC5064957.
4)

Castanares-Zapatero D, Hantson P. Pharmacological treatment of delayed cerebral ischemia and vasospasm in subarachnoid hemorrhage. Ann Intensive Care. 2011 May 24;1(1):12. doi: 10.1186/2110-5820-1-12. PMID: 21906344; PMCID: PMC3224484.
5)

Reynolds MR, Buckley RT, Indrakanti SS, Turkmani AH, Oh G, Crobeddu E, Fargen KM, El Ahmadieh TY, Naidech AM, Amin-Hanjani S, Lanzino G, Hoh BL, Bendok BR, Zipfel GJ. The safety of vasopressor-induced hypertension in subarachnoid hemorrhage patients with coexisting unruptured, unprotected intracranial aneurysms. J Neurosurg. 2015 Oct;123(4):862-71. doi: 10.3171/2014.12.JNS141201. Epub 2015 Jul 24. PubMed PMID: 26207606.
6)

Togashi K, Joffe AM, Sekhar L, Kim L, Lam A, Yanez D, Broeckel-Elrod JA, Moore A, Deem S, Khandelwal N, Souter MJ, Treggiari MM. Randomized Pilot Trial of Intensive Management of Blood Pressure or Volume Expansion in Subarachnoid Hemorrhage (IMPROVES). Neurosurgery. 2015 Feb;76(2):125-35. doi: 10.1227/NEU.0000000000000592. PubMed PMID: 25549192.

Middle cerebral artery M4 segment aneurysm

Middle cerebral artery M4 segment aneurysm

Middle cerebral artery aneurysms, are mainly found in the proximal and bifurcation tracts and only in the 1.1-1.7% of cases they are located in the M4 segment of the middle cerebral artery 1) 2) 3).

Generally, these aneurysms are secondary to traumatic brain injury and inflammatory or infectious diseases and only rarely they have idiopathic origin 4).

At present, only nine cases of ruptured cortical middle cerebral artery aneurysms have been described in literature 5) 6) 7) 8) 9) 10).

The patients are all males, except the case of Ricci et al. 11). The average age of the reported patients is 40 years. The size of the aneurysms is between 1 mm and 10 mm and, in most cases, they are saccular intracranial aneurysms or fusiform morphology. In five patients, the aneurysms present infectious etiology. Usually, they occur with ICH, sometimes associated with subarachnoid hemorrhage (SAH).

The endovascular treatment (EVT) has been performed in four cases, while the surgical treatment has been performed in three cases (two of trapping and one of clipping). In one patient, the infectious aneurysm has resolved spontaneously after antibiotic therapy. In all treatments performed, the patients have improved the neurologic symptoms and no residual aneurysms have been observed in the subsequent neuroradiology follow-up 12). Although surgery remains the main choice in the M4 aneurysms, because of the extremely distal location of them over the motor/somatosensory cortices, 13) Lv et al. 14) propose the use of the EVT in all types of the M4 aneurysms, especially after the surgery, when it is impossible to locate the small ruptured aneurysm.

The main difficulty of the surgery is the precise surgical localization of the small M4 aneurysms 15). An inaccurate localization of these vascular lesions may result in larger craniotomies and unnecessary arachnoid and pial dissections with possible resultant permanent neurological injuries 16).

In cases of aneurysms or arteriovenous malformations located at the sylvian point or at the posterior superior aspect of the insula, especially in dominant hemisphere, to reduce the dissection and open easily sylvian fissure, a logical path would follow the angular artery in the sylvian fissure cutting the arachnoid fibers and retracting only the tissues which are necessary to gain more exposure of the lesion 17).

A case of a ruptured dissecting pseudoaneurysm in the distal Middle cerebral artery (distal M3/proximal M4) prefrontal division in an healthy young patient (<60 years) successfully treated with a Pipeline Embolization Device. The PED was chosen both as the only vessel sparing option in the young patient as well as for its potential as a vessel sacrifice tool if the pseudoaneurysm was felt to be incompletely treated, which in this case was not necessary-though would have leveraged the thrombogenicity of the device as a therapeutic advantage 18).

2017

A 53-year-old female was admitted with a sudden severe headache, nausea, vomiting, and a slight left hemiparesis. The computed tomography (CT) scan showed subarachnoid hemorrhage (SAH) in the left sylvian fissure and intracerebral hemorrhage (ICH) in the left posterior parietal area. The CT angiography (CTA) reconstructed with 3D imaging showed a small saccular aneurysm in the M4 segment in proximity of the angular area. A left parieto-temporal craniotomy was performed, the aneurysm was clipped and the ICH evacuated. The motor deficit was progressively recovered. At 3-month follow-up examination, the patient was asymptomatic and feeling well.

Surgery is the best choice for the treatment of ruptured M4 aneurysms with ICH in the opinion of Ricci et al., because it allows to evacuate the hematoma and to exclude the aneurysm from the intracranial circulation. In addition, we suggest both the use of the neuronavigation technique and of the indocyanine green videoangiography (ICGV) for the aneurismal surgery 19).

2007

A 41-year-old man presented with an infarction manifesting as left-sided weakness and dysarthria. Magnetic resonance angiography revealed a subacute stage infarction in the right MCA territory and complete occlusion of the right ICA. Angiography demonstrated aneurysmal dilatation of the M4 segment of the right MCA. Surgery was performed to prevent hemorrhage from the aneurysm. The aneurysm was proximally clipped guided by Navigation-CT angiography and flow to the distal MCA was restored by superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis 20).

2005

A 20-year-old man with an intracerebral haemorrhage due to a ruptured aneurysm, which arose from a penetrating artery of the distal middle cerebral artery (MCA; M4 segment). Excision of the aneurysm was successfully achieved via a right pterional approach. The follow-up angiogram demonstrated filling of the parent vessel and no residual aneurysm. This report illustrates the angiographical finding of a penetrating artery aneurysm of the distal MCA and summarizes the previous reports to discuss their pathological and clinical characteristics 21).


1) , 4) , 5) , 21)

Ahn JY, Han IB, Joo JY. Aneurysm in the penetrating artery of the distal middle cerebral artery presenting as intracerebral haemorrhage. Acta Neurochir (Wien). 2005 Dec;147(12):1287-90; discussion 1290. Epub 2005 Aug 29. PubMed PMID: 16133768.
2) , 8) , 14)

Lv N, Zhou Y, Yang P, Li Q, Zhao R, Fang Y, Xu Y, Hong B, Zhao W, Liu J, Huang Q. Endovascular treatment of distal middle cerebral artery aneurysms: Report of eight cases and literature review. Interv Neuroradiol. 2016 Feb;22(1):12-7. doi: 10.1177/1591019915617317. Epub 2015 Dec 3. Review. PubMed PMID: 26637241; PubMed Central PMCID: PMC4757379.
3)

Elsharkawy A, Lehečka M, Niemelä M, Billon-Grand R, Lehto H, Kivisaari R, Hernesniemi J. A new, more accurate classification of middle cerebral artery aneurysms: computed tomography angiographic study of 1,009 consecutive cases with 1,309 middle cerebral artery aneurysms. Neurosurgery. 2013 Jul;73(1):94-102; discussion 102. doi: 10.1227/01.neu.0000429842.61213.d5. PubMed PMID: 23615110.
6)

Horiuchi T, Tanaka Y, Takasawa H, Murata T, Yako T, Hongo K. Ruptured distal middle cerebral artery aneurysm. J Neurosurg. 2004;100:384–8.
7)

Lee SM, Park HS, Choi JH, Huh JT. Ruptured mycotic aneurysm of the distal middle cerebral artery manifesting as subacute subduralhematoma. J Cerebrovasc Endovasc Neurosurg. 2013;15:235–40.
9) , 13) , 15) , 16)

Raza SM, Papadimitriou K, Gandhi D, Radvany M, Olivi A, Huang J. Intra-arterial intraoperative computed tomography angiography guided navigation: a new technique for localization of vascular pathology. Neurosurgery. 2012 Dec;71(2 Suppl Operative):ons240-52; discussion ons252. doi: 10.1227/NEU.0b013e3182647a73. PubMed PMID: 22858682.
10) , 11) , 12) , 19)

Ricci A, Di Vitantonio H, De Paulis D, Del Maestro M, Raysi SD, Murrone D, Luzzi S, Galzio RJ. Cortical aneurysms of the middle cerebral artery: A review of the literature. Surg Neurol Int. 2017 Jun 13;8:117. doi: 10.4103/sni.sni_50_17. eCollection 2017. PubMed PMID: 28680736; PubMed Central PMCID: PMC5482160.
17)

Ausman JI, Diaz FG, Malik GM, Tomecek F. A new microsurgical approach to cerebrovascular lesions of the sylvian point: report of two cases. Surg Neurol. 1990 Jul;34(1):48-51. PubMed PMID: 2360163.
18)

Berwanger RP, Hoover MC, Scott JA, DeNardo AJ, Amuluru K, Payner TD, Kulwin CG, Sahlein DH. The Use of a Pipeline Embolization Device for Treatment of a Ruptured Dissecting Middle Cerebral Artery M3/M4 Aneurysm: Challenges and Technical Considerations. Neurointervention. 2022 Apr 7. doi: 10.5469/neuroint.2022.00045. Epub ahead of print. PMID: 35385900.
20)

Lee SH, Bang JS. Distal Middle Cerebral Artery M4 Aneurysm Surgery Using Navigation-CT Angiography. J Korean Neurosurg Soc. 2007 Dec;42(6):478-80. doi: 10.3340/jkns.2007.42.6.478. Epub 2007 Dec 20. PubMed PMID: 19096593; PubMed Central PMCID: PMC2588183.

Rhino orbital cerebral mucormycosis

Rhino orbital cerebral mucormycosis

The second COVID-19 wave in India has been associated with an unprecedented increase in cases of COVID-19 associated mucormycosis (CAM), mainly Rhino-orbito-cerebral mucormycosis (ROCM).

Rhino orbital cerebral mucormycosis rapidly became an epidemic following the COVID-19 pandemic 1)

Gutiérrez-Delgado et al searched PubMed database from 1964 to 2014 for all available articles in the English language related to rhino-orbital-cerebral chronic infections caused by fungi of the order Mucorales and found 22 cases 2).

Rhino-orbital-cerebral mucormycosis is usually associated with a poor prognosis and is almost exclusively seen in immunocompromised patients.

59 patients were diagnosed with COVID-19 associated mucormycosis (CAM). The median duration from the first positive COVID-19 RT PCR test to the diagnosis of CAM was 17 (IQR: 12,22) days. 90% of patients were diabetic with 89% having uncontrolled sugar level (HbA1c >7%). All patients were prescribed steroids during treatment for COVID-19. 56% of patients were prescribed steroids for non-hypoxemic, mild COVID-19 (irrational steroid therapy) while in 9%, steroids were prescribed in inappropriately high dose. Patients were treated with a combination of surgical debridement (94%), intravenous liposomal Amphotericin B (91%) and concomitant oral Posaconazole (95.4%). 74.6% of patients were discharged after clinical and radiologic recovery while 25.4% died. On Relative risk analysis, COVID-19 CT severity index ≥ 18 (p=0.017), presence of orbital symptoms (p=0.002), presence of diabetic ketoacidosis (p=0.011), and cerebral involvement (p=0.0004) were associated with increased risk of death.

CAM is a rapidly progressive, angio-invasive, opportunistic fungal infection that is fatal if left untreated. The combination of surgical debridement and antifungal therapy leads to clinical and radiologic improvement in the majority of cases 3).

2015

A unique case of isolated intracranial mucormycosis of a slowly progressive nature in a healthy immunocompetent child. A 4-year-old girl with a clear medical and surgical history presented with complaints of right side facial asymmetry and unsteady gait for a period of 10 months. Clinical and radiographic investigations revealed right-sided lower motor neuron facial palsy caused by an infiltrative lesion on the right cerebellopontine angle. Initial surgical debulking was performed, a biopsy was sent for histopathological examination, and a course of prophylactic antibiotic and antifungal drugs was prescribed. The pathological report confirmed the mucormycosis fungal infection, and intravenous amphotericin B was administered for 3 weeks. One month after admission, the patient left the hospital with complete recovery. Follow-ups after 4, 8 and 12 weeks revealed no sensory or motor neurological deficits. In conclusion, this is a unique case of mucormycosis with regard to the nature and location of the infection, along with the host being a healthy child. Initial surgical exploration is a very critical step in the early diagnosis and treatment of such rare conditions 4).

2014

A 42-year-old man who developed a cerebellar mucor abscess after undergoing hematopoietic stem cell transplant for the treatment of myelodysplastic syndrome. In the post-operative period he was admitted to the neurocritical care unit and received liposomal amphotericin B intravenously and through an external ventricular drain. This patient demonstrates that utilization of an external ventricular drain for intrathecal antifungal therapy in the post-operative period may warrant further study in patients with difficult to treat intracranial fungal abscesses 5).

2013

A case of mucormycosis presenting with extensive necrosis of the maxilla with extension into the retrobulbar and infrabulbar region in an otherwise healthy patient. He underwent extensive debriding surgery followed by amphotericin B first and then oral antifungal therapy, but unfortunately, even after extensive surgery and medical treatment, he did not survive 6).

2010

Yoon et al describe a case of Rhino-orbital-cerebral (ROC) mucormycosis with pericranial abscess occurring in a female patient with uncontrolled diabetes mellitus. The infection initially developed in the right-sided nasal sinus and later progressed through the paranasal sinuses with the invasion of the peri-orbital and frontotemporal region, due to the delayed diagnosis and treatment. Numerous non-septate hyphae of the zygomycetes were identified by a punch biopsy from the nasal cavity and by an open biopsy of the involved dura. The patient was treated successfully with extensive debridement of her necrotic skull and surrounding tissues, drainage of her pericranial abscess and antifungal therapy, including intravenous amphotericin B for 61 days and oral posaconazole for the following 26 days. She returned to a normal life and has had no recurrence since the end of her treatment 15 months ago 7).

2000

A 59-year-old immunocompetent white man sustained a high-pressure water jet injury to the right inner canthus while cleaning an air conditioner filter. He later had “orbital cellulitis” develop that did not respond to antibiotics and progressed to orbital infarction. Imaging studies and biopsy results led to a diagnosis of mucormycosis. Tissue culture grew Apophysomyces elegans, a new genus of the family Mucoraceae first isolated in 1979. Orbital exenteration and radical debridement of involved adjacent structures, combined with intravenous liposomal amphotericin, resulted in patient survival.

After orbital exenteration and debridement of involved adjacent structures along with intravenous liposomal amphotericin, our patient has remained free from relapse with long-term follow-up.

The agent causing this case of rhino-orbital-cerebral mucormycosis (Apophysomyces elegans) contrasts with the three genera most commonly responsible for mucormycosis (Rhizopus, Mucor, and Absidia) in that infections with this agent tend to occur in warm climates, by means of traumatic inoculation, and in immunocompetent patients. Rhino-orbital-cerebral mucormycosis should be considered in all patients with orbital inflammation associated with multiple cranial nerve palsies and retinal or orbital infarction, regardless of their immunologic status. A team approach to management is recommended for early, appropriate surgery and systemic antifungal agents 8).


1)

Soni K, Das A, Sharma V, Goyal A, Choudhury B, Chugh A, Kumar D, Yadav T, Jain V, Agarwal A, Garg M, Bhatnagar K, Elhence P, Bhatia PK, Garg MK, Misra S. Surgical & medical management of ROCM (Rhino-orbito-cerebral mucormycosis) epidemic in COVID-19 era and its outcomes – a tertiary care center experience. J Mycol Med. 2021 Dec 25;32(2):101238. doi: 10.1016/j.mycmed.2021.101238. Epub ahead of print. PMID: 34979299.
2)

Gutiérrez-Delgado EM, Treviño-González JL, Montemayor-Alatorre A, Ceceñas-Falcón LA, Ruiz-Holguín E, Andrade-Vázquez CJ, Lara-Medrano R, Ramos-Jiménez J. Chronic rhino-orbito-cerebral mucormycosis: A case report and review of the literature. Ann Med Surg (Lond). 2016 Feb 6;6:87-91. doi: 10.1016/j.amsu.2016.02.003. eCollection 2016 Mar. PubMed PMID: 26981237; PubMed Central PMCID: PMC4776268.
3)

Dravid A, Kashiva R, Khan Z, Bande B, Memon D, Kodre A, Mane M, Pawar V, Patil D, Kalyani S, Raut P, Bapte M, Saldanha C, Chandak D, Patil T, Reddy MS, Bhayani K, Laxmi SS, Vishnu PD, Srivastava S, Khandelwal S, More S, Shakeel A, Pawar M, Nande P, Harshe A, Kadam S, Hallikar S, Kamal N, Andrabi D, Bodhale S, Raut A, Chandrashekhar S, Raman C, Mahajan U, Joshi G, Mane D. Epidemiology, clinical presentation and management of COVID-19 associated mucormycosis: A single center experience from Pune, Western India. Mycoses. 2022 Feb 25. doi: 10.1111/myc.13435. Epub ahead of print. PMID: 35212032.
4)

Al Barbarawi MM, Allouh MZ. Successful Management of a Unique Condition of Isolated Intracranial Mucormycosis in an Immunocompetent Child. Pediatr Neurosurg. 2015;50(3):165-7. doi: 10.1159/000381750. Epub 2015 May 7. PubMed PMID: 25967858.
5)

Grannan BL, Yanamadala V, Venteicher AS, Walcott BP, Barr JC. Use of external ventriculostomy and intrathecal anti-fungal treatment in cerebral mucormycotic abscess. J Clin Neurosci. 2014 Oct;21(10):1819-21. doi: 10.1016/j.jocn.2014.01.008. Epub 2014 May 19. Review. PubMed PMID: 24852901.
6)

Rahman A, Akter K, Hossain S, Rashid HU. Rhino-orbital mucourmycosis in a non-immunocompromised patient. BMJ Case Rep. 2013 Feb 6;2013. pii: bcr2012007863. doi: 10.1136/bcr-2012-007863. PubMed PMID: 23391952; PubMed Central PMCID: PMC3604437.
7)

Yoon YK, Kim MJ, Chung YG, Shin IY. Successful treatment of a case with rhino-orbital-cerebral mucormycosis by the combination of neurosurgical intervention and the sequential use of amphotericin B and posaconazole. J Korean Neurosurg Soc. 2010 Jan;47(1):74-7. doi: 10.3340/jkns.2010.47.1.74. Epub 2010 Jan 31. PubMed PMID: 20157385; PubMed Central PMCID: PMC2817523.
8)

Fairley C, Sullivan TJ, Bartley P, Allworth T, Lewandowski R. Survival after rhino-orbital-cerebral mucormycosis in an immunocompetent patient. Ophthalmology. 2000 Mar;107(3):555-8. PubMed PMID: 10711895.
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