Cervical Spinal Cord Stimulation in Patients With Cerebral Vasospasm After Subarachnoid Haemorrhage: VasoStim Study

Study Overview
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Brief Summary
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Cerebral vasospasm is characterized by a vasoconstriction of cerebral arteries causing a reduction of cerebral blood flow (CBF) and leading to ischemia and infarction of the brain parenchyma. Cerebral vasospasm is a serious complication of aneurysmal subarachnoid hemorrhage (SAH) with high morbidity and overall mortality of 40-50%. Although the exact mechanisms of spinal cord stimulation (SCS) on the innervation of cerebral vessels are still unclear, several hypotheses have been formulated and studies in animals and human performed with very promising results. This is a proof of concept study to better understand the effect and mechanisms of cervical spinal cord stimulation on cerebral vasospasm after aneurysmal SAH in human.

Detailed Description
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Cerebral vasospasm is characterized by a vasoconstriction of cerebral arteries causing a reduction of cerebral blood flow (CBF) and leading to ischemia and infarction of the brain parenchyma. Cerebral vasospasm is a serious complication of aneurysmal subarachnoid hemorrhage (SAH) with high morbidity and overall mortality of 40-50%. The exact pathophysiological mechanisms underlying cerebral vasospasm are still not known in detail. A wide range of different therapeutic options with various efficacies are available, triple-H therapy and endovascular treatment options like intra-arterial application of vasodilators e.g. Nimodipine or Papaverine or transluminal balloon angioplasty have been reported and are applied to prevent and treat cerebral vasospasm after SAH. Calcium channel blockers such as nimodipine or nicardipine improve outcome in patients after SAH and reduce the risk of secondary ischemia. The benefit of the different therapies is undoubted, but there is still potential for improvement concerning the rate of morbidity and mortality. Although the exact mechanisms of spinal cord stimulation (SCS) on the innervation of cerebral vessels are still unclear, several hypotheses have been formulated and studies in animals and human performed with very promising results. This is a proof of concept study to better understand the effect and mechanisms of cervical spinal cord stimulation on cerebral vasospasm after aneurysmal SAH in human. Subjects are enrolled into the study, if radiographical vasospasms are detected in CTA, CTP, cerebral angiography or TCD. SCS leads are implanted within 12h after study enrolment following the investigator's standard practice. SCS will be continuously delivered until day 14 after SAH. Doppler ultrasound is performed before SCS lead implantation and repeated after implantation on a daily basis and appearance of a new neurological deficit device until 24h after stopping the stimulation. Efficacy of cervical SCS is further evaluated by CTA or angiography and CTA/P performed 48h and 96h after lead implantation, as well as on day 14 after SAH before stopping the stimulation. The SCS electrode(s) are explanted on day 15. Intracerebral pressure is monitored from day 7-15. Headache, measured as NRS 0-10 and the consumption of analgesics are monitored from day 7-15, at discharge, at 3 and 6 months.

Official Title
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Cervical Spinal Cord Stimulation in Patients With Cerebral Vasospasm After Subarachnoid Haemorrhage: VasoStim Study

Conditions
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Cerebral Vasospasm, Subarachnoid Hemorrhage

Intervention / Treatment
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* Device: Spinal cord stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fisher 3 grade subarachnoid hemorrhage at presentation Secured aneurysm by clipping or coiling Is 18-75 years of age at the time of enrollment Cerebral vasospasm: Cerebral angiography o Narrowing of vessel lumen > 66% Transcranial Doppler ultrasound Mean flow velocity > 150 cm/s or Lindegaard Index > 3 or increase > 50 cm/s within 24 hours Intracranial CT angiography o Narrowing of vessel lumen > 66% Intracranial CT perfusion o Time To Drain (TTD) > 4.7 seconds Is willing and capable of providing informed consent or existence of the presumed will of the patient by a relative or a legal representative Written confirmation by a study independent physician to guarantee patient interest Is willing and capable of complying with the study related requirements, procedures, and visits No findings on spinal imaging preventing SCS lead implantation Negative pregnancy test No breast feeding Exclusion Criteria: Untreated ruptured aneurysm Cerebral infarction in the territory of the spastic arteries or massive disseminated infarction Signs of cerebral herniation Uncontrollable intracranial pressure Infection Coagulation disorder Is participating in another interventional trial Circulatory instability Severe congestive heart failure Patients with an elevated risk of bleeding Known allergy to implanted materials (Silicon, Titanium)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cervical spinal cord stimulation on cerebral vasospasm after aneurysmal SAH<br>Cervical spinal cord stimulation on cerebral vasospasm after aneurysmal SAH | Device: Spinal cord stimulation<br>* Cervical spinal cord stimulation on cerebral vasospasm after aneurysmal SAH<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of baseline flow velocity | The change of baseline flow velocity from the onset of vasospasm to day 14 assessed with Doppler ultrasound showing the effect of cervical SCS. | 14 days after onset vasospasm | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vasospasm changes in angiography and perfusion in CTP | Vasospasm changes in angiography and perfusion in CTP | 48 hours after stimulation | 
| Vasospasm changes in CTA and perfusion in CTP | Vasospasm changes in CTA and perfusion in CTP | 48 hours after stimulation | 
| Vasospasm changes in angiography and perfusion in CTP | Vasospasm changes in angiography and perfusion in CTP | 96 hours after stimulation | 
| Vasospasm changes in CTA and perfusion in CTP | Vasospasm changes in CTA and perfusion in CTP | 96 hours after stimulation | 
| Vasospasm changes in CTA and perfusion in CTP | Vasospasm changes in CTA and perfusion in CTP | 14 days after stimulation | 
| Vasospasm changes in angiography and perfusion in CTP | Vasospasm changes in angiography and perfusion in CTP | 14 days after stimulation | 
| Triple-H therapy | Development of symptomatic vasospasm from onset to day 14 with need for Triple-H therapy | 14 days after stimulation | 
| Angioplasty or intra-arterial application of vasodilators | Development of symptomatic vasospasm from onset to day 14 with need for angioplasty or intra-arterial application of vasodilators | 14 days after stimulation | 
| Intracerebral pressure (ICP) | Intracerebral pressure (ICP) | Day 7- 14 | 
| Headache | Headache measured by VAS Scale (Score 0-10 with 0 representing no pain, and 10 maximum pain intensity) | Day 7- 14 | 
| Consumption of analgesics | Consumption of analgesics | Day 7- 14 | 
| Side effects of SCS | Side effects of SCS | Day 7- 14 |