Brain Circuitry Changes in Central Poststroke Pain: a Clinical and Neuroimaging Study

Central poststroke pain (CPP) is estimated to affect up to 10% of stroke patients and is one of the most difficult-to-treat conditions with a detrimental effect on patient's quality of life. So far, no drug has proven efficient to alleviate CPP and neuromodulation approaches including Deep Brain Stimulation (DBS) and motor-cortex stimulation have yielded mixed results with only a few patients experiencing long-term pain relief. To date, little is known about the pathophysiology of CPP. There is at present little evidence for a clear association between the specific location of lesions, clinical manifestation and phenomenology of pain as well as treatment response of CPP patients. Furthermore, the time delay between stroke occurrence and CPP occurrence is highly variable and the fact, that it is not immediate in the great majority of patients suggests that other factors contribute to the development of CPP. These factors have not been identified yet.

Study Overview

• Status: Recruiting
• Conditions: Pain; CPP
• Intervention / Treatment: Procedure: Clinical Testing

Detailed Description

Central poststroke pain (CPP) is estimated to affect up to 10% of stroke patients and is one of the most difficult-to-treat conditions with a detrimental effect on patient's quality of life. So far, no drug has proven efficient to alleviate CPP and neuromodulation approaches including DBS and motor-cortex stimulation have yielded mixed results with only a few patients experiencing long-term pain relief. To date, little is known about the pathophysiology of CPP. There is at present little evidence for a clear association between the specific location of lesions, clinical manifestation and phenomenology of pain as well as treatment response of CPP patients. Furthermore, the time delay between stroke occurrence and CPP occurrence is highly variable and the fact, that it is not immediate in the great majority of patients suggests that other factors contribute to the development of CPP. These factors have not been identified yet.

The objective of this research project is to correlate clinical aspects of CPP (pain phenomenology) with magnetic resonance image (MRI)-based findings, especially metabolic changes and functional reorganization processes captured by functional MRI and MR spectroscopy. A better understanding of the underlying pathophysiological mechanism of CPP and its involved neuronal networks are mandatory for any future therapeutic approach to treat this difficult condition. The discovery of a potential image-based biomarker could serve to help identify patients early who are at risk of developing CPP. Furthermore, the findings may help identify prognosticators of different forms of CPP treatments (e.g. biofeed-back, neuromodulation approaches, medication) in the future.

• Study Type: Interventional
• Enrollment (Estimated): 88
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Andreas Nowacki, MD; Phone Number: +41316322409; Email: andreas.nowacki@insel.ch
• Study Contact Backup: Name: Claudio Pollo, MD; Phone Number: 28034766; Email: claudio.pollo@insel.ch

Study Locations

• Switzerland
  • Bern, Switzerland, 3000
    • Recruiting
    • Dep. of Neurosurgery, Bern University Hospital
    • Contact: Andreas Nowacki, MD; Phone Number: +41 31 632 2409; Email: andreas.nowacki@insel.ch
    • Contact: Claudio Pollo, MD; Phone Number: +41 31 632 2409; Email: claudio.pollo@insel.ch
    • Sub-Investigator: Andreas Nowacki, MD
    • Principal Investigator: Claudio Pollo, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria patients:

• Patients with a haemorrhagic or ischemic stroke affecting the somatosensory system as defined by both CT or MRI and clinical criteria
• Patient age between 18-75 years
• Signed written informed consent

Exclusion Criteria patients:

• Secondary stroke due to a cerebral vascular malformation or tumor
• Patients with aphasic syndromes and impaired verbal communication, complete sensory-motor hemi-neglect and restrictions of the ability to report on their pain and cooperate during sensory testing
• Patients with severe stroke NIHSS > 14 and or Modified Rankin Scale (MRS) > 3
• History of severe myelopathy or polyneuropathy with clinical sensory deficits and history of neuropathic pain
• Widespread stroke size due to internal carotid artery-occlusion or more than one main territory (anterior, middle or posterior cerebral artery)
• Contraindication for 7T MRI (metallic implant, tattoo, claustrophobia, etc.)
• In case of women < 45 years of age: pregnancy

Inclusion Criteria for healthy volunteers

• Informed consent as documented by signature
• Age: ≥18 years and ≤ 75 years

Exclusion criteria for healthy volunteers

• Pregnancy and breastfeeding
• Contraindication for 7T MRI (metallic implant, tattoo, claustrophobia, etc.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with central poststroke pain	Procedure: Clinical Testing; Clinical testing for neurological deficits based on National Institute of Health Stroke Scale (NIHSS), objective sensory testing and pain assessment by quantitative sensory testing (QST) and quantitative pain drawings, 7T magnetic resonance imaging (MRI)
Experimental: Patients without central poststroke pain	Procedure: Clinical Testing; Clinical testing for neurological deficits based on National Institute of Health Stroke Scale (NIHSS), objective sensory testing and pain assessment by quantitative sensory testing (QST) and quantitative pain drawings, 7T magnetic resonance imaging (MRI)
Active Comparator: healthy controls; healthy volunteers	Procedure: Clinical Testing; Clinical testing for neurological deficits based on National Institute of Health Stroke Scale (NIHSS), objective sensory testing and pain assessment by quantitative sensory testing (QST) and quantitative pain drawings, 7T magnetic resonance imaging (MRI)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between cerebral connectivity patterns	Correlation between cerebral connectivity patterns at rest during pain-processing tasks based on functional MRI	Day 30 after inclusion

Collaborators and Investigators

• Sponsor: Insel Gruppe AG, University Hospital Bern
• Investigators: Principal Investigator: Claudio Pollo, MD, Inselspital Bern, Department of Neurosurgery

Publications and helpful links

General Publications

• Bowsher D. Central pain: clinical and physiological characteristics. J Neurol Neurosurg Psychiatry. 1996 Jul;61(1):62-9. doi: 10.1136/jnnp.61.1.62.
• Bowsher D, Leijon G, Thuomas KA. Central poststroke pain: correlation of MRI with clinical pain characteristics and sensory abnormalities. Neurology. 1998 Nov;51(5):1352-8. doi: 10.1212/wnl.51.5.1352.
• Karahanoglu FI, Van De Ville D. Transient brain activity disentangles fMRI resting-state dynamics in terms of spatially and temporally overlapping networks. Nat Commun. 2015 Jul 16;6:7751. doi: 10.1038/ncomms8751.
• Preti MG, Bolton TA, Van De Ville D. The dynamic functional connectome: State-of-the-art and perspectives. Neuroimage. 2017 Oct 15;160:41-54. doi: 10.1016/j.neuroimage.2016.12.061. Epub 2016 Dec 26.

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2022
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: April 12, 2022
• First Submitted That Met QC Criteria: April 12, 2022
• First Posted (Actual): April 19, 2022

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 12, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 2020-02640

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No