Occipital nerve stimulation for headache disorders

Occipital nerve stimulation (ONS) was originally described in the treatment of occipital neuralgia. However, the spectrum of possible indications has expanded in recent years to include primary headache disorders, such as migraine and cluster headaches. Retrospective and some prospective studies have yielded encouraging results, and evidence from controlled clinical trials is emerging, offering hope for refractory headache patients. In this article we discuss the scientific rationale to use ONS to treat headache disorders, with emphasis on the trigeminocervical complex. ONS is far from a standardized technique at the moment and the recent literature on the topic is reviewed, both with respect to the procedure and its possible complications. An important way to move forward in the scientific evaluation of ONS to treat refractory headache is the clinical phenotyping of patients to identify patients groups with the highest likelihood to respond to this modality of treatment. This requires multidisciplinary assessment of patients. The development of ONS as a new treatment for refractory headache offers an exciting prospect to treat our most disabled headache patients. Data from ongoing controlled trials will undoubtedly shed new light on some of the unresolved questions

Magnetic resonance spectroscopy in migraine: what have we learned so far?

Objective: To summarize and evaluate proton (H-1) and phosphorus (P-31) magnetic resonance spectroscopy (MRS) findings in migraine. Methods: A thorough review of H-1 and/or P-31-MRS studies in any form of migraine published up to September 2011. Results: Some findings were consistent in all studies, such as a lack of ictal/interictal brain pH change and a disturbed energy metabolism, the latter of which is reflected in a drop in phosphocreatine content, both in the resting brain and in muscle following exercise. In a recent interictal study ATP was found to be significantly decreased in the occipital lobe of migraine with aura patients, reinforcing the concept of a mitochondrial component to the migraine threshold, at least in a subgroup of patients. In several studies a correlation between the extent of the energy disturbance and the clinical phenotype severity was apparent. Less consistent but still congruent with a disturbed energy metabolism is an observed lactate increase in the occipital cortex of several migraine subtypes (MwA, migraine with prolonged aura). No increases in brain glutamate levels were found. Conclusion: The combined abnormalities found in MRS studies imply a mitochondrial component in migraine neurobiology. This could be due to a primary mitochondrial dysfunction or be secondary to, for example, alterations in brain excitability. The extent of variation in the data can be attributed to both the variable clinical inclusion criteria used and the variation in applied methodology. Therefore it is necessary to continue to optimize MRS methodology to gain further insights, especially concerning lactate and glutamate

Calcium signaling in and between brain astrocytes and endothelial cells

Two in vitro co-culture models of the blood-brain barrier (BBB) were developed using primary rat cortical astrocytes and ECV304 endothelial cells or primary rat brain capillary endothelial cells. We showed that intercellular calcium (Ca2+) waves can mediate bidirectional astrocyte-endothelial Call signal communication in both co-culture models. It appears that two signaling pathways are involved. A first mechanism is related to intercellular diffusion of the Ca2+ mobilizing messenger inositoltrisphosphate (IP3) through gap junctions as studied with flash photolysis of caged-IP3. A second pathway involves extracellular diffusion of a purinergic messenger as studied with the purinergic inhibitors apyrase and suramin. Using gap junction-deficient HeLa cells and connexin-GFP transfected HeLa cells, the existence Of the two Ca2+ signaling pathways mentioned was confirmed and their subcellular characteristics and differences were further studied. We also suggest that astrocytic intercellular Call waves may be accompanied by and contribute to some of the ionic shifts observed in the brain upon traumatic brain injury. Further work will be needed to confirm our data in brain slices or even in the brain in vivo, and to establish the role and function of intercellular Ca2+ signals at the BBB

Chronic cluster headache and the pituitary gland

Background: Cluster headache is classified as a primary headache by definition not caused by an underlying pathology. However, symptomatic cases of otherwise typical cluster headache have been reported. Case presentation: A 47-year-old male suffered from primary chronic cluster headache (CCH, ICHD-3 beta criteria fulfilled) since the age of 35 years. A magnetic resonance imaging (MRI) study of the brain in 2006 came back normal. He tried several prophylactic treatments but was never longer than 1 month without attacks. He was under chronic treatment with verapamil with only a limited effect on the attack frequency. Subcutaneous sumatriptan 6 mg injections were very effective in aborting attacks. By February 2014 the patient developed a continuous interictal pain ipsilateral to the right-sided cluster headache attacks. An indomethacin test (up to 225 mg/day orally) was negative. Because of the change in headache pattern we performed a new brain MRI, which showed a cystic structure in the pituitary gland. The differential diagnosis was between a Rathke cleft cyst and a cystic adenoma. Pituitary function tests showed an elevated serum prolactin level. A dopamine agonist (cabergoline) was started and the headache subsided completely. Potential pathophysiological mechanisms of pituitary tumor-associated headache are discussed. Conclusion: Neuroimaging should be considered in all patients with CCH, especially those with an atypical presentation or evolution. Response to acute treatment does not exclude a secondary form of cluster headache. There may be shared pathophysiological mechanisms of primary and secondary cluster headache

To control or not? A motivational perspective on coping with pain

Pain relief is often the primordial treatment objective in pain patients. However, an exclusive focus upon pain relief may have costs. Evidence is accumulating that persistent attempts to gain control over pain may, paradoxically, hinder successful adaptation to pain and increase frustration and limitations due to pain. To better understand these apparently paradoxical findings, we propose to adopt a motivational perspective on coping with pain. Within this perspective, pain control is recast as an attempt to protect and restore valued life goals threatened by pain. This framework explains why some patients engage excessively in pain control strategies despite the costs associated with this, such as overuse of medication. A clinical implication is that cautiousness is warranted in promoting strategies exclusively aimed at pain relief. Beyond standard medical care, interventions should also be aimed at the improvement of functioning despite pain. Certainly those patients for whom there is no definite or sound cure to pain and who increasingly experience emotional and physical problems due to pain might benefit from paramedical help by psychologists and/or physiotherapists

Saccade behaviour in migraine patients

Background: Voxel-based morphometry studies in migraine patients showed significant grey matter volume reduction in regions involved in the control of saccadic eye movements. We hypothesized that these changes would be reflected in dysfunctional saccadic behaviour. Methods: Saccades were recorded by infrared oculography using three different paradigms (pro-saccade with gap, prosaccade overlap and anti-saccade with gap). We compared the results for migraine patients (n = 80) with those for controls (n = 87). Results: No significant differences were found between migraine patients with (n = 46) and without (n = 34) aura. Migraine patients showed a saccadic behaviour that differed from controls in three respects. In migraine patients, the latencies in the pro-saccade with gap paradigm were borderline significantly longer. Moreover, in both the pro-saccade with gap and the pro-saccade overlap paradigm we observed a larger intra-individual variation of the latency in migraine patients. However, the biggest difference was that the patients who received migraine prophylactic therapy made significantly more anti-saccade errors in the anti-saccade with gap paradigm, suggesting that inhibitory saccade control is impaired in migraine patients depending on the severity of the migraine. Conclusion: We suggest a deficient inhibitory control, reflecting an executive dysfunction in the dorsolateral prefrontal cortex or a dysfunction in the cingulate cortex, is present in migraine patients