Continuous direct intraarterial treatment of meningitis-induced vasospasm in a pediatric patient: illustrative case

Aubrey C Rogers Department of Neurosurgery, Albany Medical Center, Albany, New York

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Aditya D Goyal Department of Neurosurgery, Albany Medical Center, Albany, New York

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Alexandra R Paul Department of Neurosurgery, Albany Medical Center, Albany, New York

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BACKGROUND

Bacterial meningitis–induced ischemic stroke continues to cause significant long-term complications in pediatric patients. The authors present a case of severe right internal carotid artery terminus and M1 segment vasospasm in a 9-year-old with an infected cholesteatoma, which was refractory to multiple intraarterial treatments with verapamil and milrinone. This is the first report of continuous intraarterial antispasmodic treatment in a pediatric patient as well as the first report of continuous treatment in an awake and extubated patient.

OBSERVATIONS

Arterial narrowing was successfully treated by continuous direct intraarterial administration of both a calcium channel blocker (verapamil) and a phosphodiesterase-3 inhibitor (milrinone). The patient recovered remarkably well and was discharged home with no neurological deficit (National Institutes of Health Stroke Scale score 0) and ambulatory without assistance after 22 days. The authors report a promising outcome of this technique performed in a pediatric patient.

LESSONS

This represents a novel treatment option for the prevention of stroke in pediatric bacterial meningitis. Continuous, direct intraarterial administration of antispasmodic medications can successfully prevent long-term neurological deficit in pediatric meningitis-associated vasospasm. The described method has the potential to significantly improve outcomes in severe pediatric meningitis-associated vasospasm.

ABBREVIATIONS

CT = computed tomography; CTA = computed tomography angiography; IA = intraarterial; ICA = internal carotid artery; ICU = intensive care unit; MCA = middle cerebral artery; MRI = magnetic resonance imaging; NIHSS = National Institutes of Health Stroke Scale; PDE-3 = phosphodiesterase-3

BACKGROUND

Bacterial meningitis–induced ischemic stroke continues to cause significant long-term complications in pediatric patients. The authors present a case of severe right internal carotid artery terminus and M1 segment vasospasm in a 9-year-old with an infected cholesteatoma, which was refractory to multiple intraarterial treatments with verapamil and milrinone. This is the first report of continuous intraarterial antispasmodic treatment in a pediatric patient as well as the first report of continuous treatment in an awake and extubated patient.

OBSERVATIONS

Arterial narrowing was successfully treated by continuous direct intraarterial administration of both a calcium channel blocker (verapamil) and a phosphodiesterase-3 inhibitor (milrinone). The patient recovered remarkably well and was discharged home with no neurological deficit (National Institutes of Health Stroke Scale score 0) and ambulatory without assistance after 22 days. The authors report a promising outcome of this technique performed in a pediatric patient.

LESSONS

This represents a novel treatment option for the prevention of stroke in pediatric bacterial meningitis. Continuous, direct intraarterial administration of antispasmodic medications can successfully prevent long-term neurological deficit in pediatric meningitis-associated vasospasm. The described method has the potential to significantly improve outcomes in severe pediatric meningitis-associated vasospasm.

ABBREVIATIONS

CT = computed tomography; CTA = computed tomography angiography; IA = intraarterial; ICA = internal carotid artery; ICU = intensive care unit; MCA = middle cerebral artery; MRI = magnetic resonance imaging; NIHSS = National Institutes of Health Stroke Scale; PDE-3 = phosphodiesterase-3

Bacterial meningitis is a significant source of morbidity and mortality in the pediatric population. Although the introduction of the Haemophilus influenza and pneumococcal vaccines have contributed to an 86% decline in the incidence of bacterial meningitis, the mortality rate remains high at roughly 15% in pediatric patients.1 Mortality is further increased in cases in which the hospital course is complicated by ischemic stroke.2,3 Despite advances in management, up to one-half of the children in such cases experience long-term neurological sequelae; 10% of survivors have severe neurological deficits including deafness, motor deficits, and seizures.4,5 Angiographic imaging in bacterial meningitis demonstrates vessel wall irregularities, focal dilatations, arterial occlusions, and arterial beading.6 The pathophysiology is attributable to a combination of vasculitis, vasospasm, and thrombosis.7 Screening tools and secondary stroke prevention practices have been developed for the management of pediatric meningitis-associated stroke8,9; however, the reported guidelines for intraarterial management of meningitis-induced vasospasm are very limited. Endovascular treatment of pediatric stroke has become more prevalent, and mechanical thrombectomy for large vessel occlusions is considered a level C evidence class IIb recommendation for patients aged 1 to 18 years old.10 Endovascular techniques have also been used in neonates in the treatment of vein of Galen malformations.

The administration of intraarterial antispasmodics has been well demonstrated to be beneficial for aneurysmal subarachnoid hemorrhage–associated vasospasm.11 This treatment has translated to occasional use for bacterial meningitis–associated vasospasm in adults, as described in several case reports.12–14 The continuous administration of intraarterial antispasmodics is not the current standard of care but has been described in severe cases of persistent vasospasm due to subarachnoid hemorrhage in adults. These instances of continuous antispasmodic treatment over multiple days are certainly not routine and have never been documented in younger patients.15 In this paper, we present a pediatric case of meningitis-associated vasospasm, refractory to repeat intraarterial antispasmodic treatments but responded to prolonged continuous intraarterial administration via a catheter that remained in the cervical segment of the internal carotid artery (ICA) for 5 days.

Illustrative Case

Initial Presentation and Hospital Course

A previously healthy 9-year-old female presented to the emergency department 1 week after developing right ear pain that progressed to include fevers, right-sided headache, right-sided neck pain, nausea and vomiting, an inability to maintain oral intake, photophobia, and weight loss. Initial laboratory results were remarkable for leukocytosis of 19.2 10 × 3/µL, and computed tomography (CT) scanning demonstrated a left-sided cholesteatoma. Follow-up magnetic resonance imaging (MRI) demonstrated a complicated cholesteatoma with meningeal enhancement in that region (Fig. 1). Both blood and cerebrospinal fluid cultures were positive for Streptococcus pneumoniae. The patient underwent a left mastoidectomy and was treated with antibiotics. On the ninth day of her hospital stay (postoperative day 1), the patient developed left-sided hemiplegia and hemineglect. Computed tomography angiography (CTA) demonstrated severe narrowing of the distal right ICA and proximal middle cerebral artery (MCA; National Institutes of Health Stroke Scale [NIHSS] score 10; Fig. 2).

FIG. 1
FIG. 1

Axial contrast-enhanced T1-weighted MRI of the brain demonstrating a peripherally enhancing destructive mass lesion in the left tympanomastoid region, measuring 2.1 × 1.6 cm. There is corresponding enhancing, likely reactive dural thickening, along the adjacent inferior temporal gyri.

FIG. 2
FIG. 2

CTA performed after the patient developed left-sided weakness, demonstrating focal narrowing of the right ICA terminus and M1 branches.

Endovascular Interventions

The patient was taken emergently for diagnostic angiography under general anesthesia. Images of the right ICA confirmed severe vasospasm of the distal right ICA and proximal MCA. We administered 20 mg verapamil and 6 mg milrinone to the right ICA, with improvement of the vasospasm. Postprocedure MRI demonstrated an infarct within the right basal ganglia and corona radiata but with sparing of most of the ICA/MCA territory (Fig. 3). The patient was extubated and had improvement in her weakness and neglect. Unfortunately, later that same day, she again became hemiplegic with dense hemineglect and was taken back for another emergent angiography under general anesthesia; 20 mg verapamil and 5 mg milrinone were administered to the right ICA. Balloon angioplasty was attempted, but the area of vasospasm could not be successfully crossed with the balloon. The patient again had improvement with the intraarterial treatment and was antigravity in her upper and lower extremity. Unfortunately, overnight her symptoms worsened, and she was taken emergently for her third intraarterial treatment (20 mg intraarterial verapamil and 10 mg milrinone). Given the patient’s need for frequent repeat treatment, the decision was made to leave a 4-Fr angle diagnostic catheter within the cervical right ICA for continuous intraarterial infusion of verapamil and milrinone. The diagnostic catheter was stabilized within a 4-Fr short sheath, which was sutured in place at the groin. An appropriate rate of infusion was calculated based on the time between the redevelopment of ischemic symptoms. The infusion delivered 1.6 mg/hr verapamil, 0.4 mg/hr of milrinone, and 320 units of heparin per hour (40 mg verapamil, 10 mg milrinone, and 8,000 units heparin in 1 L normal saline infused at a rate of 40 mL/hr). The short sheath was also placed on continuous flush with heparinized saline at a low rate to prevent thrombus and retain patency of the sheath. The patient remained intubated and sedated and underwent 24 hours of continuous direct infusion in the pediatric intensive care unit (ICU). Repeat angiography was performed 24 hours later and showed significant improvement of the vasospasm (Fig. 4). The decision was made to exchange the 4-Fr diagnostic catheter for a Renegade HI-FLO microcatheter to decrease the risk of injury to the ICA in an awake patient. The microcatheter was stabilized within the 4-Fr short sheath using a standard micropuncture kit dilator to provide more stability. Both the sheath and microcatheter were sutured to the leg and dressed with Tegaderm. The sheath was placed on flush at a rate of 5 mL/hr to prevent thrombus formation. The patient was extubated, which allowed for monitoring of her response to the infusion based on neurological examination. The previously described dose of intraarterial infusion was continued for 48 hours longer. The patient remained antigravity without neglect. The infusion was then gradually weaned with close monitoring of the patient’s neurological examination. For 36 hours, the patient received 0.4 mg milrinone and 320 units heparin per hour (10 mg milrinone and 8,000 units heparin in 1 L normal saline infused at a rate of 40 mL/hr). The antispasmodic treatment was then discontinued, and the patient underwent 24 hours of continuous infusion with heparinized saline alone through the microcatheter to prevent thrombus formation. The patient’s neurological examination remained stable during the wean and discontinuation of the verapamil and milrinone. She underwent a final angiography study 1 week after her initial stroke, and the catheter and sheath were subsequently removed. The angiography was scheduled to take a final image of the vessels. Given her clinically improved examination, she did not undergo any further MRI.

FIG. 3
FIG. 3

MRI of the brain prior to diffusion restriction right caudate head, right putamen and right corona radiata extending to the centrum semiovale.

FIG. 4
FIG. 4

Right ICA angiography, anteroposterior view. A: Initial angiography prior to any intraarterial treatment, demonstrating vasospasm of distal ICA and proximal MCA. B: Angiography after three intraarterial treatments and 24 hours of continuous intraarterial treatment, demonstrating some improvement in vasospasm. C: Final angiography after a total of 108 hours of continuous intraarterial treatment and 24 hours of heparinized saline infusion to ensure no recurrence of symptoms, demonstrating significant improvement in the vasospasm. Note the worse image quality because the patient was not intubated and immobilized for the final procedure.

Patient Informed Consent

The necessary patient informed consent was obtained in this study.

Discussion

Observations

The patient continued to be monitored very closely for clinical symptoms of vasospasm. Fortunately, she did not require further treatment. She recovered remarkably well and was able to be discharged home from the hospital 22 days after her initial presentation with no neurological deficit (NIHSS score 0) and ambulatory without assistance.

Lessons

The pathophysiology of ischemic stroke in bacterial meningitis is multifactorial and includes a combination of vasculitis, vasospasm, and thrombosis. We describe a unique case in which we were able to successfully treat the arterial narrowing by continuous direct intraarterial administration of both a calcium channel blocker (verapamil) and a phosphodiesterase-3 (PDE-3) inhibitor (milrinone). These are both standard of care at our institution for the intraarterial treatment of vasospasm. Milrinone has been shown to be effective in meningitis-associated vasospasm that is resistant to intraarterial verapamil.12 In addition to their muscle-relaxing mechanism of action, PDE-3 inhibitors also exhibit antiinflammatory and antiplatelet properties.16 By using both medications, we simultaneously targeted multiple underlying mechanisms.

The vasodilatory effect of intraarterial antispasmodic treatment lasts less than 2 hours in studies.17 By administering the medications continuously, the need for repeat procedures can be avoided. However, there are several reported side effects and complications associated with continuous intraarterial treatment, including longer rates of ICU stays, thrombus formation at both the groin and distal catheter, and infections.18,19 The most frequent side effect is systemic hypotension.15 Our patient did require systemic pressors while she was under general anesthesia for procedures and during the time that she was intubated and sedated for continuous intraarterial infusion. However, when the patient was extubated and awake, she was able to tolerate continuous intraarterial treatment without the need for pressors. In prior reported cases of continuous intraarterial treatment in the setting of vasospasm secondary to subarachnoid hemorrhage, patients were intubated and sedated while the catheter was left in place.18,20 Our ability to have the patient awake during treatment represents a significant step toward making the treatment safer. The risk of pneumonia and urinary tract infection was also decreased by having the patient extubated and awake during her treatment. Heparin was included in the infusion, and the sheath was on continuous infusion with heparin-saline to prevent thrombus formation.

Endovascular treatment in the pediatric patient population has been increasing in frequency with the treatment of ischemic stroke. There are some inherent challenges in the treatment of this population, recognizing the fact that the equipment used is designed for adults and not specific to pediatrics.

Acute bacterial meningitis is still associated with significant morbidity and mortality in pediatric populations despite advances in vaccination and medical management. The incidence of bacterial meningitis decreased by 55% with the introduction of the Haemophilus influenza vaccine and decreased by another 31% with the introduction of the pneumococcal vaccine.1 The current incidence of bacterial meningitis in children ranges from 0.2 to 3.7 cases per 100,000 persons.17 Unfortunately, the mortality rate remains as high as 15% and is higher in patients who suffer an ischemic stroke as part of their clinical course.2,3 For stroke survivors, both the patients and their families have a lower quality of life.21 We demonstrate with this case that continuous direct intraarterial administration of antispasmodic medications may be a treatment option to prevent long-term neurological deficit in pediatric meningitis-associated vasospasm. In severe cases of pediatric vasospasm, the described method has the potential to significantly improve outcomes and quality of life for a vulnerable population, with otherwise high morbidity.

Author Contributions

Conception and design: Paul, Rogers. Acquisition of data: Rogers. Analysis and interpretation of data: Paul, Rogers. Drafting the article: Paul, Rogers. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Paul. Study supervision: Paul.

References

  • 1

    Thigpen MC, Whitney CG, Messonnier NE, et al. Bacterial meningitis in the United States, 1998–2007. N Engl J Med. 2011;364(21):20162025.

  • 2

    Dunbar M, Shah H, Shinde S, et al. Stroke in pediatric bacterial meningitis: population-based epidemiology. Pediatr Neurol. 2018;89:1118.

  • 3

    Swanson D Meningitis. Pediatr Rev. 2015;36(12):514526.

  • 4

    Chandran A, Herbert H, Misurski D, Santosham M Long-term sequelae of childhood bacterial meningitis: an underappreciated problem. Pediatr Infect Dis J. 2011;30(1):36.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Edmond K, Clark A, Korczak VS, Sanderson C, Griffiths UK, Rudan I Global and regional risk of disabling sequelae from bacterial meningitis: a systematic review and meta-analysis. Lancet Infect Dis. 2010;10(5):317328.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Shulman JG, Cervantes-Arslanian AM Infectious etiologies of stroke. Semin Neurol. 2019;39(4):482494.

  • 7

    Murala S, Nagarajan E, Bollu PC Infectious causes of stroke. J Stroke Cerebrovasc Dis. 2022;31(4):106274.

  • 8

    Boelman C, Shroff M, Yau I, et al. Antithrombotic therapy for secondary stroke prevention in bacterial meningitis in children. J Pediatr. 2014;165(4):799806.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Fonseca Y, Tshimanga T, Ray S, et al. Transcranial Doppler ultrasonographic evaluation of cerebrovascular abnormalities in children with acute bacterial meningitis. Front Neurol. 2021;11:558857.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Bhatia K, Kortman H, Blair C, et al. Mechanical thrombectomy in pediatric stroke: systematic review, individual patient data meta-analysis, and case series. J Neurosurg Pediatr. 2019;24(5):558571.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Hoh BL, Ko NU, Amin-Hanjani S, et al. 2023 Guideline for the Management of Patients With Aneurysmal Subarachnoid Hemorrhage: A Guideline From the American Heart Association/American Stroke Association. Stroke. 2023;54(7):e314-e370.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Norman S, Rosenberg J, Sundararajan SH, Al Balushi A, Boddu SR, Ch’ang JH Management of refractory bacterial meningitis-associated cerebral vasospasm: illustrative case. J Neurosurg Case Lessons. 2023;5(7):CASE22418.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Taqui A, Koffman L, Hui F, et al. Intra-arterial vasodilator therapy for parainfectious cerebral vasospasm. J Neurol Sci. 2014;340(1-2):225229.

  • 14

    Nussbaum ES, Lowary J, Nussbaum LA A multidisciplinary approach to the treatment of severe cerebral vasospasm following bacterial meningitis: A case report and literature review. Surg Neurol Int. 2015;6:148.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Viderman D, Sarria-Santamera A, Bilotta F Side effects of continuous intra-arterial infusion of nimodipine for management of resistant cerebral vasospasm in subarachnoid hemorrhage patients: a systematic review. Neurochirurgie. 2021;67(5):461469.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Abbott-Banner KH, Page CP Dual PDE3/4 and PDE4 inhibitors: novel treatments for COPD and other inflammatory airway diseases. Basic Clin Pharmacol Toxicol. 2014;114(5):365376.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Lim J, Cho YD, Kwon HJ, et al. Duration of vasodilatory action after intra-arterial infusions of calcium channel blockers in animal model of cerebral vasospasm. Neurocrit Care. 2021;34(3):867875.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Anthofer J, Bele S, Wendl C, et al. Continuous intra-arterial nimodipine infusion as rescue treatment of severe refractory cerebral vasospasm after aneurysmal subarachnoid hemorrhage. J Clin Neurosci. 2022;96:163171.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    von der Brelie C, Doukas A, Stopfer A, et al. Clinical course and monitoring parameters after continuous interventional intra-arterial treatment in patients with refractory cerebral vasospasm. World Neurosurg. 2017;100:504513.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Wolf S, Martin H, Landscheidt JF, Rodiek SO, Schürer L, Lumenta CB Continuous selective intraarterial infusion of nimodipine for therapy of refractory cerebral vasospasm. Neurocrit Care. 2010;12(3):346351.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Sporns PB, Fullerton HJ, Lee S, et al. Childhood stroke. Nat Rev Dis Primers. 2022;8(1):12.

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  • FIG. 1

    Axial contrast-enhanced T1-weighted MRI of the brain demonstrating a peripherally enhancing destructive mass lesion in the left tympanomastoid region, measuring 2.1 × 1.6 cm. There is corresponding enhancing, likely reactive dural thickening, along the adjacent inferior temporal gyri.

  • FIG. 2

    CTA performed after the patient developed left-sided weakness, demonstrating focal narrowing of the right ICA terminus and M1 branches.

  • FIG. 3

    MRI of the brain prior to diffusion restriction right caudate head, right putamen and right corona radiata extending to the centrum semiovale.

  • FIG. 4

    Right ICA angiography, anteroposterior view. A: Initial angiography prior to any intraarterial treatment, demonstrating vasospasm of distal ICA and proximal MCA. B: Angiography after three intraarterial treatments and 24 hours of continuous intraarterial treatment, demonstrating some improvement in vasospasm. C: Final angiography after a total of 108 hours of continuous intraarterial treatment and 24 hours of heparinized saline infusion to ensure no recurrence of symptoms, demonstrating significant improvement in the vasospasm. Note the worse image quality because the patient was not intubated and immobilized for the final procedure.

  • 1

    Thigpen MC, Whitney CG, Messonnier NE, et al. Bacterial meningitis in the United States, 1998–2007. N Engl J Med. 2011;364(21):20162025.

  • 2

    Dunbar M, Shah H, Shinde S, et al. Stroke in pediatric bacterial meningitis: population-based epidemiology. Pediatr Neurol. 2018;89:1118.

  • 3

    Swanson D Meningitis. Pediatr Rev. 2015;36(12):514526.

  • 4

    Chandran A, Herbert H, Misurski D, Santosham M Long-term sequelae of childhood bacterial meningitis: an underappreciated problem. Pediatr Infect Dis J. 2011;30(1):36.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Edmond K, Clark A, Korczak VS, Sanderson C, Griffiths UK, Rudan I Global and regional risk of disabling sequelae from bacterial meningitis: a systematic review and meta-analysis. Lancet Infect Dis. 2010;10(5):317328.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Shulman JG, Cervantes-Arslanian AM Infectious etiologies of stroke. Semin Neurol. 2019;39(4):482494.

  • 7

    Murala S, Nagarajan E, Bollu PC Infectious causes of stroke. J Stroke Cerebrovasc Dis. 2022;31(4):106274.

  • 8

    Boelman C, Shroff M, Yau I, et al. Antithrombotic therapy for secondary stroke prevention in bacterial meningitis in children. J Pediatr. 2014;165(4):799806.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Fonseca Y, Tshimanga T, Ray S, et al. Transcranial Doppler ultrasonographic evaluation of cerebrovascular abnormalities in children with acute bacterial meningitis. Front Neurol. 2021;11:558857.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Bhatia K, Kortman H, Blair C, et al. Mechanical thrombectomy in pediatric stroke: systematic review, individual patient data meta-analysis, and case series. J Neurosurg Pediatr. 2019;24(5):558571.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Hoh BL, Ko NU, Amin-Hanjani S, et al. 2023 Guideline for the Management of Patients With Aneurysmal Subarachnoid Hemorrhage: A Guideline From the American Heart Association/American Stroke Association. Stroke. 2023;54(7):e314-e370.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Norman S, Rosenberg J, Sundararajan SH, Al Balushi A, Boddu SR, Ch’ang JH Management of refractory bacterial meningitis-associated cerebral vasospasm: illustrative case. J Neurosurg Case Lessons. 2023;5(7):CASE22418.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Taqui A, Koffman L, Hui F, et al. Intra-arterial vasodilator therapy for parainfectious cerebral vasospasm. J Neurol Sci. 2014;340(1-2):225229.

  • 14

    Nussbaum ES, Lowary J, Nussbaum LA A multidisciplinary approach to the treatment of severe cerebral vasospasm following bacterial meningitis: A case report and literature review. Surg Neurol Int. 2015;6:148.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Viderman D, Sarria-Santamera A, Bilotta F Side effects of continuous intra-arterial infusion of nimodipine for management of resistant cerebral vasospasm in subarachnoid hemorrhage patients: a systematic review. Neurochirurgie. 2021;67(5):461469.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Abbott-Banner KH, Page CP Dual PDE3/4 and PDE4 inhibitors: novel treatments for COPD and other inflammatory airway diseases. Basic Clin Pharmacol Toxicol. 2014;114(5):365376.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Lim J, Cho YD, Kwon HJ, et al. Duration of vasodilatory action after intra-arterial infusions of calcium channel blockers in animal model of cerebral vasospasm. Neurocrit Care. 2021;34(3):867875.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Anthofer J, Bele S, Wendl C, et al. Continuous intra-arterial nimodipine infusion as rescue treatment of severe refractory cerebral vasospasm after aneurysmal subarachnoid hemorrhage. J Clin Neurosci. 2022;96:163171.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    von der Brelie C, Doukas A, Stopfer A, et al. Clinical course and monitoring parameters after continuous interventional intra-arterial treatment in patients with refractory cerebral vasospasm. World Neurosurg. 2017;100:504513.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Wolf S, Martin H, Landscheidt JF, Rodiek SO, Schürer L, Lumenta CB Continuous selective intraarterial infusion of nimodipine for therapy of refractory cerebral vasospasm. Neurocrit Care. 2010;12(3):346351.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Sporns PB, Fullerton HJ, Lee S, et al. Childhood stroke. Nat Rev Dis Primers. 2022;8(1):12.

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