Dagny Holle

Gray matter changes related to chronic posttraumatic headache

Background: Although up to 15% of patients with whiplash injury develop chronic headache, the basis and mechanisms of this posttraumatic headache are not well understood. Methods: Thirty-two patients with posttraumatic headache following whiplash injury were investigated within 14 days after the accident and again after 3 months using magnetic resonance–based voxel-based morphometry. Twelve patients developed chronic headache lasting longer than 3 months and were studied a third time after 1 year. Results: Patients who developed chronic headache revealed decreases in gray matter in the anterior cingulate and dorsolateral prefrontal cortex after 3 months. These changes resolved after 1 year, in parallel to the cessation of headache. The same patients who developed chronic headache showed an increase of gray matter in antinociceptive brainstem centers, thalamus, and cerebellum 1 year after the accident. Conclusion: We demonstrate adaptive gray matter changes of pain processing structures in patients with chronic posttraumatic headache in regard to neuronal plasticity, thus providing a biologically plausible basis for this common, disabling problem.

Gray matter volume reduction reflects chronic pain in trigeminal neuralgia.

Trigeminal neuralgia (TN) is supposedly caused by an ectatic blood vessel affecting the trigeminal nerve at the root entry zone of the brain stem. Recent evidence suggests an additional central component within trigeminal pain-processing in the pathophysiology of TN. Therefore, we aimed to identify specific brain regions possibly associated with the development or maintenance of TN using magnetic resonance imaging (MRI) voxel-based morphometry (VBM). Sixty patients with classical TN were compared to 49 healthy controls. Eighteen patients had TN with concomitant constant facial pain, a condition previously described as a predictor of worse treatment outcome. We found gray matter (GM) volume reduction in TN patients compared to healthy controls in the primary somatosensory and orbitofrontal cortices, as well as the in the secondary somatosensory cortex, thalamus, insula, anterior cingulate cortex (ACC), cerebellum, and dorsolateral prefrontal cortex. GM volume decrease within the ACC, parahippocampus, and temporal lobe correlated with increasing disease duration in TN. There were no differences comparing patients with and without concomitant constant facial pain. No GM increase was found comparing patient subgroups with each other and with healthy controls. The observed changes probably reflect the impact of multiple, daily attacks of trigeminal pain in these patients similar to what was previously described in other chronic pain conditions and may be interpreted as adaptation mechanism to chronic pain in regard to neuronal plasticity. The ACC, parahippocampus and temporal lobe volume reduction in parallel with disease duration may point to a pivotal role of these structures in chronic pain.

New therapeutic approaches for the prevention and treatment of migraine

The management of patients with migraine is often unsatisfactory because available acute and preventive therapies are either ineffective or poorly tolerated. The acute treatment of migraine attacks has been limited to the use of analgesics, combinations of analgesics with caffeine, ergotamines, and the triptans. Successful new approaches for the treatment of acute migraine target calcitonin gene-related peptide (CGRP) and serotonin (5-hydroxytryptamine, 5-HT1F) receptors. Other approaches targeting the transient receptor potential vanilloid (TRPV1) receptor, glutamate, GABAA receptors, or a combination of 5-HT1B/1D receptors and neuronal nitric oxide synthesis have been investigated but have not been successful in clinical trials thus far. In migraine prevention, the most promising new approaches are humanised antibodies against CGRP or the CGRP receptor. Non-invasive and invasive neuromodulation approaches also show promise as both acute and preventive therapies, although further studies are needed to define appropriate candidates for these therapies and optimum protocols for their use.

Differences in clinical characteristics and frequency of accompanying migraine features in episodic and chronic cluster headache

Introduction: Data on clinical differences between episodic (eCH) and chronic cluster headache (cCH) and accompanying migraine features are limited. Methods: History and clinical features of 209 consecutive cluster headache patients (144 eCH, 65 cCH; male:female ratio 3.4 : 1) were obtained in a tertiary headache centre by face-to-face interviews. Relationship between occurrence of accompanying symptoms, pain intensity, comorbid migraine, and circannual and circadian rhythmicity was analysed. Results: 99.5% of patients reported a minimum of one ipsilateral cranial autonomic symptom (CAS); 80% showed at least three CAS. A seasonal rhythmicity was observed in both eCH and cCH. A comorbid headache disorder occurred in 25%. No significant difference was detected between patients with comorbid migraine and without regarding occurrence of phonophobia, photophobia or nausea during cluster attacks. Patients with comorbid migraine reported allodynia significantly (p = 0.022) more often during cluster attacks than patients without comorbid migraine. Conclusion: Occurrence of CAS and attack frequency, as well as periodic patterns of attacks, are relatively uniform in eCH and cCH. Multiple CAS are not related to pain intensity. Allodynia during cluster attacks is a frequent symptom. The unexpectedly high rate of accompanying migrainous features during cluster attacks cannot be explained by comorbid migraine.

Hypothalamic gray matter volume loss in hypnic headache.

Hypnic headache (HH) is a rare primary headache disorder characterized by strictly nocturnal headache attacks that mostly occur at the same time at night. The pathophysiology of this disease is poorly understood, but hypothalamic involvement was suspected as the hypothalamus represents the cerebral management center of sleep regulation and pain control.

Modulation of human trigeminal and extracranial nociceptive processing by transcranial direct current stimulation of the motor cortex

Objective: The study was conducted to investigate the after-effect of transcranial direct current stimulation (tDCS) applied over the human primary motor cortex (M1) on trigeminal and extracranial nociceptive processing. Basic procedures: Nineteen healthy volunteers were stimulated using cathodal, anodal (both 1 mA) or sham tDCS for 20 minutes. Pain processing was assessed by recording trigeminal and extracranial pain-related evoked potentials (PREPs) following electrical stimulation of the contralateral forehead and hand at baseline, 0, 20 and 50 minutes post-tDCS. Main findings: Cathodal tDCS resulted in decreased peak-to-peak amplitudes (PPAs) by 18% while anodal tDCS lead to increased PPAs of PREPs by 35% (p < .05). Principal conclusions: The decreased PPAs suggest an inhibition and the increased PPAs of PREPs suggest an excitation of trigeminal and extracranial pain processing induced by tDCS of the M1. These results may provide evidence for the effectiveness of tDCS as a therapeutic instrument in treating headache disorders.

Medication-overuse headache: risk factors, pathophysiology and management

Medication-overuse headache (MOH) is defined by the International Classification of Headache Disorders as a headache in patients with a pre-existing primary headache disorder that occurs on ≥15 days per month for >3 months, and is caused by overuse of medication intended for acute or symptomatic headache treatment. The prevalence of MOH in the general population is around 1%, but the condition is much more common in people with headache, in particular chronic migraine. The phenotype of the headache in MOH depends on the initial primary headache and the type of overused acute medication. In this Review, we will discuss the epidemiology, risk factors, pathophysiology, prevention and treatment of MOH. Treatment of MOH is performed in three steps: educating patients about the relationship between frequent intake of acute headache medication and MOH with the aim to reduce intake of acute medication; initiation of migraine prevention (such as topiramate or onabotulinumtoxin A in migraine) in patients who fail step 1; detoxification on an outpatient basis or in a day hospital or inpatient setting, depending on severity and comorbidities. The success rate of treatment is around 50–70%, although patients whose MOH is associated with opioid overuse have higher relapse rates. In all patients with MOH, relapse rates can be reduced by patient education and care in the follow-up period.

Integrated multidisciplinary care of headache disorders: A narrative review:

Background Recent evidence shows that multidisciplinary treatment is effective in chronic pain syndromes, especially in headache disorders. Aim The aim of this review is to summarize current knowledge on integrative care concepts in headache patients regarding the optimal and necessary treatment parts, optimal duration and setting. Methods We present a narrative review reporting current literature and personal experience. Results and conclusion Based on current knowledge, multidisciplinary treatment programs appear to be reasonable and efficient in headache disorders. Sufficient controlled studies regarding the need for individual parts of the integrative care approach are missing as yet. Recommendations are therefore at least partly based on personal experiences. It seems to be unambiguous that patients should be referred to a specialized headache center offering such a program instead of being sent sequentially to various medical specialists. The extent and kind of required therapy (e.g. personal consultation versus group sessions) is not known yet. All patients should learn relaxation training, although it is unclear yet which training is the best for which patient. Physiotherapy with guidance on more activity and individual exercises should be used in all patients. Some patients might benefit from cognitive behavioral therapy. However, therapies often depend more on country-specific health care systems than on clinical needs or scientific data.

Trigeminal neuralgia and persistent idiopathic facial pain

Trigeminal neuralgia (TN) and persistent idiopathic facial pain (PIFP) are two of the most puzzling orofacial pain conditions and affected patients are often very difficult to treat. TN is characterized by paroxysms of brief but severe pain followed by asymptomatic periods without pain. In some patients a constant dull background pain may persist. This constant dull pain sometimes makes the distinction from PIFP difficult. PIFP is defined as continuous facial pain, typically localized in a circumscribed area of the face, which is not accompanied by any neurological or other lesion identified by clinical examination or clinical investigations. The pain usually does not stay within the usual anatomic boundaries of the trigeminal nerve distribution and is a diagnosis of exclusion. Epidemiologic evidence on TN, and even more so on PIFP, is quite scarce, but generally both conditions are considered to be rare diseases. The etiology and underlying pathophysiology of TN, and more so PIFP, remain unknown. Treatment is based on only few randomized controlled clinical trials and insufficiently evaluated surgical procedures.

Serial polysomnography in hypnic headache.

Background: Hypnic headache (HH) is a rare primary headache disorder characterized by strictly sleep-related headache attacks. Most patients are over the age of 50 and usually awake at the same time at night with dull bilateral head pain. The pathophysiology of this headache disorder is still enigmatic but association with rapid eye movement (REM) sleep and sleep-disordered breathing (SDB) has been suggested. Methods: Six patients with HH according to the current International Classification of Headache Disorders (ICHD-II) criteria (code 4.5) were investigated. Serial polysomnography (PSG) was performed in each patient for four consecutive nights. Results: A total of 22 HH attacks were recorded from all patients during PSG. Six of the monitored headache attacks arose from REM sleep; 16 attacks, however, arose from different non-REM (NREM) sleep stages. Five patients showed an increased apnoea/hypopnoea index (>5), indicating obstructive sleep apnoea (OSA) on some but not the majority of nights. Headache onset and occurrence of SDB were not temporally connected. Conclusions: This prospective study shows that the onset of HH was not associated with sleep stage. These results contradict the current belief that REM sleep and SDB play a crucial role in the pathophysiology of HH.