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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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CPP, Pain

Intervention / Treatment
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* Procedure: Clinical Testing


Participation Criteria
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Eligibility Criteria
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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.)

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with central poststroke pain<br>Patients with central poststroke pain | Procedure: Clinical Testing<br>* 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)<br>|
| Experimental: Patients without central poststroke pain<br>Patients without central poststroke pain | Procedure: Clinical Testing<br>* 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)<br>|
| Active Comparator: healthy controls<br>healthy volunteers | Procedure: Clinical Testing<br>* 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)<br>|

What is the study measuring?
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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 |