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

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.

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.

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.)