Mark Obermann

Medication-overuse headache.

PURPOSE OF REVIEW Medication-overuse headache (MOH) is a well described clinical entity. There is a growing body of knowledge on the epidemiology of MOH, risk factors, and treatment strategies. RECENT FINDINGS The International Headache Society updated the classification criteria for MOH. Population-based studies provided an insight into the prevalence and peculiarities of MOH patients in eastern Europe and Asia. Large-scaled population-based longitudinal studies made it possible to analyze risk factors leading to the development of MOH. Imaging studies helped to better understand the pathophysiology of headache chronicity. New treatment strategies have been suggested. SUMMARY MOH is a common headache disorder and a serious public health problem all over the world. Although the treatment regimen for MOH patients is straightforward and the outcomes are favorable, it is time now to move forward and establish a predictive model for early recognition of patients at high risk, to intervene early and avoid development of chronic headache.

Morphometric changes of sensorimotor structures in focal dystonia

Idiopathic cervical dystonia (CD) and benign essential blepharospasm (BEB) are the most common forms of focal dystonia. Previous autopsy and imaging studies suggested that these disorders are not accompanied by structural brain abnormalities. However, recent brain voxel‐based morphometry (VBM) studies of these conditions suggest that there actually may be changes in gray matter. The objective of this stdy was to detect possible gray matter abnormalities in patients with CD and BEB using VBM and to compare the results between the two conditions and with age‐ and gender‐matched controls. High‐resolution MRI was employed to evaluate healthy controls and individuals with BEB and CD. Eleven BEB, 9 CD, and 14 healthy control subjects were imaged. VBM revealed alterations of gray matter structures involved in sensorimotor processing in the individuals with focal dystonia. In CD subjects there was increased gray matter in the thalamus, caudate head bilaterally, superior temporal lobe, and left cerebellum, while gray matter was decreased in the putamen bilaterally. BEB subjects had increased gray matter in the caudate head and cerebellum bilaterally as well as decrease in the putamen and thalamus bilaterally. These findings strongly underline the recent notion that idiopathic focal dystonias might have a detectable structural correlate. They also demonstrate structural similarities of the investigated focal dystonias, possibly reflecting a shared common pathophysiological origin.

Central sensitization of the trigeminal and somatic nociceptive systems in medication overuse headache mainly involves cerebral supraspinal structures.

Trigeminal and somatic nociceptive systems were studied in controls (n = 15), episodic migraine (n = 16), analgesics (n = 14) and triptan-induced medication overuse headache (MOH) (n = 15) before and after withdrawal. Patients with MOH and comorbid depressive symptoms and depression without headache were studied to investigate the influence of depression. Trigeminal nociception was studied by simultaneous registration of pain-related cortical potentials (PREP) and nociceptive blink reflex (nBR) following nociceptive-specific electrical stimulation of the forehead. Somatic nociception was evaluated using PREP of upper limbs. We found facilitation of both trigeminal and somatic PREP but not of nBR in MOH, which normalized after withdrawal. No differences were found comparing analgesics vs. triptan MOH. No differences were observed between controls and patients with episodic migraine and depression without headache. A transient facilitation was found of trigeminal and somatic nociceptive systems in MOH, which was more pronounced on a supraspinal level.

Impaired trigeminal nociceptive processing in patients with trigeminal neuralgia

Background: Trigeminal neuralgia (TN) usually leads to paroxysms of short lasting but very severe pain. Between the attacks the patient is usually asymptomatic, but a constant dull background pain may persist in some cases. The mechanisms associated with the development of this chronic pain are not well understood. Objective: To determine trigeminal nociceptive fiber impairment in patients with TN comparing symptomatic and nonsymptomatic sides using the nociceptive blink reflex (nBR) and pain-related evoked potentials (PREP) and to identify possible central mechanisms of pain chronicity. Methods: We investigated 24 patients with TN without and 18 patients with TN with concomitant chronic facial pain. PREP and nBR were investigated following nociception specific electrical stimulation on both sides of the face and in each division of the trigeminal nerve (V1, V2, and V3). Results: We found prolonged PREP and nBR latencies and reduced amplitudes comparing symptomatic and nonsymptomatic sides in all patients with TN. In patients with chronic facial pain, however, PREP amplitudes were larger and latencies shorter compared to patients with TN without facial pain, while nBR results were similar across groups. Conclusion: The data suggest an impairment of the trigeminal nociceptive system due to demyelination and/or axonal dysfunction on the symptomatic side and locate this defect close to the root entry zone in the brainstem. Moreover, central facilitation of trigeminal nociceptive processing was observed in patients with trigeminal neuralgia with concomitant chronic facial pain indicating overactivation of central sensory transmission. This may represent a possible adaptive mechanism for the development of chronic pain.

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.

Prevalence of Trigeminal Autonomic Symptoms in Migraine: A Population-Based Study

Epidemiological data on trigeminal unilateral autonomic symptoms in patients with migraine are scarce. The authors wanted to provide a population-based evaluation of the prevalence of unilateral autonomic features in migraine patients and an assessment of the expression of unilaterality of autonomic symptoms and head pain in patients with UAs compared to other migraine patients. A population based sample of 6000 inhabitants of the city of Essen in Germany was screened using a previously validated standard questionnaire. Three thousand three hundred and sixty subjects (56% of a total 6000) responded. 841 subjects had migraine, out of which 226 reported accompanying unilatral auetonomic symptoms (26.9%, CI 95% [23.9-30%]). Unilateral autonomic symptoms in patients with migraine are common and have been widely underestimated in the past. One out of four migraine patients regularly experiences one or more unilateral autonomic symptoms during their attack. Migraine patients with accompanying autonomic symptoms seem to experience their pain more unilateral and more severe than non-UA patients.

Efficacy of pregabalin in the treatment of trigeminal neuralgia

This prospective, open-label study aimed to evaluate the efficacy of pregabalin treatment in patients suffering from trigeminal neuralgia with and without concomitant facial pain. Fifty-three patients with trigeminal neuralgia (14 with concomitant chronic facial pain) received pregabalin (PGB) 150-600 mg daily and were prospectively followed for 1 year. The primary outcome was number of patients pain free or with reduction of pain intensity by > 50% and of attack frequency by > 50% after 8 weeks. Secondary outcome was sustained pain relief after 1 year. Thirty-nine patients (74%) improved after 8 weeks with a mean dose of 269.8 mg/day (range 150-600 mg/day) PGB: 13 (25%) experienced complete pain relief and 26 (49%) reported pain reduction > 50%, whereas 14 (26%) did not improve. Patients without concomitant facial pain showed better response rates (32 of 39, 82%) compared with patients with concomitant chronic facial pain (7 of 14, 50%, P = 0.020). Concomitant chronic facial pain appears to be a clinical predictor of poor treatment outcome. PGB appears to be effective in the treatment of trigeminal neuralgia.

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.

Prevalence of trigeminal neuralgia and persistent idiopathic facial pain: A population-based study

Objective: To estimate the lifetime prevalence of trigeminal neuralgia (TN) and persistent idiopathic facial pain (PIFP) in a population-based sample in Germany. Methods: A total of 3336 responders of 6000 contacted inhabitants of the city of Essen in Germany were screened using a self-assessment questionnaire. 327 individuals, who reported recurrent facial pain and randomly selected 150 (5% of 3009) screening negative subjects, received a phone interview by one of six neurologists and if necessary a face-to-face examination. Those with suspected TN or PIFP following the phone interview underwent neurological examination by two neurologists who were unaware of the presumed diagnosis. A random group of 25 (10% of 247) phone interview negative subjects was examined face-to-face. All suspected cases of PIFP received otorhinolaryngological examination and diagnostic cranial magnetic resonance imaging (MRI). In TN patients the number of vessel-nerve contacts was determined by thin-slice cranial MRI. Results: Lifetime prevalence of TN was estimated to be 0.3% [10 of 3336; 95% CI 0.1–0.5%], of PIFP 0.03% [1 of 3336; 95% CI < 0.08%]. Thin-slice cranial MRI detected five vessel-nerve contacts and no symptomatic lesions in the 10 TN patients. Conclusions: This large population-based study revealed that TN and PIFP are rare facial pain disorders.

Correlation of epidermal nerve fiber density with pain-related evoked potentials in HIV neuropathy

&NA; HIV associated sensory neuropathy is a common neurological disorder with reported prevalence of 53%. When only small fibers are involved, the diagnosis of neuropathy remains difficult since standard nerve conduction studies generally are unremarkable. We assessed a method to identify small‐fiber neuropathy using electrically evoked pain‐related potentials and correlated the electrophysiological results with intraepidermal nerve fiber density in patients with HIV associated sensory neuropathy. Nineteen HIV positive patients were investigated for clinically diagnosed peripheral neuropathy with Neuropathy Symptoms Score (NSS) ⩾ 3 and Neuropathy Disability Score (NDS) ⩾ 5. Nine healthy HIV negative control subjects were recruited. We performed standard nerve conduction testing, electrically evoked pain‐related potentials and skin biopsy in all participants. Pain‐related evoked potentials revealed abnormalities in all HIV positive neuropathy patients, while standard nerve conduction testing was abnormal in eight patients only. Pain‐related evoked potential latencies and amplitudes strongly correlated with intraepidermal nerve fiber density. The method of pain‐related evoked potential conduction appears to be a sensitive, fast, non‐invasive technique for the detection of small‐fiber neuropathy and may prove to become a valuable diagnostic asset.