Ana Ruela 1263919 CecĂlia Nunes 1263897 Joana Rodrigues 1263935
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Cluster Headache • "Cluster headache is probably the worst pain that humans experience. (...) Women with cluster headache will tell you that an attack is worse than giving birth. (..). It's just awful” Dr. Peter Goadsby, Professor of Clinical Neurology at University College London • "Our patients were disabled by the disorder and suffered from bouts of pain from two to twenty times a week. They had found no relief from the usual methods of treatment. Their pain was so severe that several of them had to be constantly watched for fear of suicide. (..).“ Dr. B.T Horton, from his paper on cluster headache,1939
Cluster Headache – – – – – –
Neurovascular disease that involves an immense degree of pain Also called “suicide headache” The real cause of this disease remains unknown Affects 0.1%- 0.2% of the population Men are more affected than women The two main forms • Episodic • Chronic – Circadian and circannual rythmicity
Patients use words such as "excruciating," "explosive," and "deep"
Management • Drug treatment • Oxigen therapy • Triptans
10-15% of all CH patients are refractory to either some or all medication
• Destructive surgery – Option for people who have not been helped with standard therapy. – Interruption of the trigeminal sensory or autonomic pathways – Severe complications: Diplopia, Anaethesia Dolorosa, Jaw deviation, Corneal Ulcers. • Neurostimulation – Has emerged as a therapeutic option for select patients. • Hypothalamic Deep Brain Stimulation • Occipital Nerve Stimulation • Spinal Cord Stimulation
Pathways in CH F A C E
Brainstem Trigeminal nerve Other facial nerves
Trigeminal Nucleus Dorsal hors and columns
Thalamus (sensory map of the body)
Symptoms: Pain/Vasodilatation Autonomic features Occipital nerve
Spinal cord
Suprachiasmatic nucleus Hypothalamus
BACK OF HEAD
BODY
Cortex (Perception and modulation)
About CH (1) • PET in during CH attacks repeatedly showed activation of: – areas related to pain modulation and perception – inferior posterior hypothalamus (PH) ipsilateral to the attacks
• (Increased neuronal density in PH) • PH is activated and supressed when
Hypothalamus involvement (inferior posterior nuclei)
About CH (2) Ok, the hypothalamus is involved Generator or terminator? • 1980 ‘s hypothesis: generator • However – Positive hypothalamic stimulation does not trigger an attack – Negative hypothalamic stimulation does not block an attack – Other pain modulating areas are activated in CH attacks
• Current thoughts: terminator, but we really don’t know…
About CH (3) • Volume of the cavernous sinus loggia may be smaller in CH patients • Sympathetic, parasympathetic and sensory fibers of the trigeminal nerve intersect here • Autonomic features of disease •Unilateral • Peripheral vasoconstrictor agonists may terminate attacks
Peripheral trigger (local inflammation cavernous sinus)
does not explain central features
• Lowered testerone, LH, melatonin levels, particularly during cluster periods • Circadian and circannual recurrence
Central trigger (Hypothalamus and suprachiasmatic nucleus)
Research Question • What are the differences in the firing patterns between an ongoing CH attack and a basal state, in the inferior posterior hypothalamus (IPH) neurons and the suprachiasmatic nucleus (SCN) neurons of CCH patients?
Research Proposal (1) • Long-Term Microelectrode Recording of PH and SCN action potential activity, followed by hypothalamic stimulation for the treatment of CH.
Research Proposal (2) • Microarray of recording electrodes in the SCN and in the PH • Stimulating lead in the PH (established target for CH DBS) • Recording electrodes ON and stimulating electrode OFF for 3 days (3 x 24h), after implantation • Recording electrodes OFF and stimulating electrode ON, for long-term PH stimulation • Signal processing of the firing patterns
Microarray of recording eletrodes Stimulating electrodes
Research Proposal (3) • Anatomical Positioning of the electrodes – MRI provides anatomical details – PH: Stereotactic coordinates used previously in the literature for hypothalamic stimulation. – SCN: MRI coordinates or coordinates available in the literature. Adapt MRI and stereotactic positioning in a CT scan.
Research Proposal (4) • Monitoring 3-5 patients’ everyday life – awake-sleep cycle – time and duration of CH attacks – Three days (3 times x 24h) • Patient Selection – Patients with chronic CH for at least 2 years, according to the International Headache Society (IHS) diagnostic criteria for CH (2004). – Age between 18 and 75. – At least 6 debilitating headaches per week – No relief from prophylactic and abortive therapies. – Successful completion of daily headache diaries over a one month period prior to surgery – Failure of ONS for at least one year
Electric Activity of SCN • Neurons fire in a 24-hour rhythm • Maximum firing rate at 12h am • Falls again during the night
PH recordings in the literature •During surgical procedure as a exploring method, before stimulation electrodes implantation •Only obtained for patients in basal conditions (not experiencing an attack)
•Activity in the PH is always expected •Pulsation artifact is frequent •Average firing rate of 20 Hz
What do we expect to find? • Altered firing rate/amplitude in the CH preceding or during CH attacks? • Differentiated firing patterns in light-induced SCN and 24h SCN. • Relation between time of the day-CH onset?
What’s next? • Evaluate and compare remission period activity in drugresistant episodic CH - Longer recording time. • How does the SCN communicate with the pathways of CH pain? • Regulation of the Genetic Expression in SCN by light…? – Ventrolateral SCN – Dorsomedial SCN
• • • • •
Biodegradable recording microelectrodes? Same electrode for PH recording and stimulating? Stimulation of SCN? Modulatory activity of the hypothalamus? Use of the implanted electrodes to measure action potentials in other experimental settings in these patients.
What do you think?