Steffen Naegel

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.

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.

Central vestibular system modulation in vestibular migraine

Background Vestibular migraine affects 1% of the general population, and 30%–50% of all migraine patients describe occasionally associated vertigo or dizziness. We aimed to identify brain regions altered in vestibular migraine in order to evaluate the connection between migraine and the vestibular system. Methods Seventeen patients with definite vestibular migraine were compared to 17 controls using magnetic resonance imaging-based voxel-based morphometry. Results We found grey matter (GM) volume reduction in the superior, inferior and middle (MT/V5) temporal gyrus as well as in the mid. cingulate, dorsolateral prefontal, insula, parietal and occipital cortex. A negative correlation of disease duration and GM volume was observed in areas associated with pain and vestibular processing. Moreover, there was a negative correlation between headache severity and prefrontal cortex volume. Conclusion Alterations identified in vestibular migraine resemble those previously described for migraine, but also extend to areas involved in multisensory vestibular control and central vestibular compensation possibly representing the pathoanatomic connection between migraine and the vestibular system.

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.

Clinical characteristics and therapeutic options in hypnic headache

Background: Hypnic headache (HH) is a rare primary headache disorder that is characterized by exclusively sleep-related headache attacks. Because of its low prevalence, clinical features and therapeutic options are widely unknown or under discussion. Methods: Twenty patients with HH were examined and interviewed using a standardized questionnaire in regard to their clinical characteristics and effective treatment regimens. Data were evaluated according to current International Headache Society (IHS) diagnostic criteria. Individual treatment history and effective treatment options were compared with expected efficacy based on current literature. Results: In conflict to current IHS criteria, 15% of patients reported trigemino-autonomic symptoms. All patients showed distinct motor behavior during their headache attacks. In acute pain attacks caffeine was most effective. Lithium, topiramate, melatonin, amitriptyline and indomethacin were sometimes useful prophylactic treatment options but were often associated with side effects. Conclusions: Our results underline the need for modification of the IHS diagnostic criteria of HH to better reflect the actual clinical characteristics of this headache. Caffeine should be considered as first-line acute therapy. Prophylactic medical treatment should be carefully evaluated in regard to side effects in this aged patient population, as this seems to be a major concern of patients apart from pure pain reduction.

Cortical plasticity in episodic and chronic cluster headache

Cluster headache (CH) is characterized by recurrent episodes of excruciatingly painful, unilateral headache attacks typically accompanied by trigeminal autonomic symptoms. Due to its rhythm with alternating episodes of pain and no-pain, it is an excellent model to investigate whether structural brain changes detected by magnetic resonance based voxel-based-morphometry (VBM) reflect the cause of the disease, may be a consequence of the underlying disease other than pain, or may simply be caused by the sensation of pain itself. We investigated 91 patients with CH in different stages of their disease using VBM and compared them to 78 age- and gender-matched healthy controls. We detected distinct regional gray matter (GM) changes in different brain regions including the temporal lobe, the hippocampus, the insular cortex and the cerebellum. The extent, location and direction of observed GM alterations depended on the state of disease and appeared dynamic in relation to pain state (i.e., pain vs. no-pain). No hypothalamic changes were detected in CH patients compared to healthy controls. The GM changes observed in this study are highly dynamic and thereby reflect the cortical plasticity of the brain in regard to pain. This observed dynamic may provide an explanation of the diverse results of previous VBM studies in pain. Regarding CH the results suggest that the disease is more likely to be caused by a network dysfunction rather than by a single malfunctioning structure.

Habituation of the nociceptive blink reflex in episodic and chronic cluster headache.

Background: Analysis of habituation patterns in patients with primary headache disorders allows the detection of changes to the excitability level of the trigeminal nociceptive system. Previous studies demonstrated a habituation deficit to painful stimuli in migraine and it was suggested that similar observations could be made in cluster headache (CH). Methods: Habituation of the “nociceptive” blink reflex (nBR) (R2 response) was studied in 66 CH patients (18 episodic CH inside bout, 28 episodic CH outside bout, 20 chronic CH) as well as in 30 healthy controls in a case-control study design. Results: Habituation behaviour was similar in CH and healthy controls as well as in CH subtypes. No side-to-side differences of habituation between headache side and non-headache side were detected. Conclusion: Our results did not detect an altered habituation in CH patients. Despite clinical similarities, migraine and CH seem not to share the same pathophysiological mechanisms in this regard.

Topiramate in the prevention and treatment of migraine: efficacy, safety and patient preference

Migraine is a very common disorder characterized by the combination of typical headache with associated autonomic symptoms and/or the presence of aura. Considerable advances have been made in recent years to understand the pathophysiology of migraine, which has led to improved treatment options for the acute migraine attack as well as migraine prophylaxis. Unfortunately, preventive treatment is often insufficient to decrease migraine frequency substantially or is not well tolerated. Topiramate is an antipileptic drug with a complex mode of action which has proven its efficacy and safety in the prophylactic treatment of episodic migraine in a number of randomized controlled clinical trials. Topiramate is also effective in treating patients with chronic migraine. It has little pharmacological interaction with other drugs and is generally well tolerated by patients.

Persistent Postural-Perceptual Dizziness: A Matter of Higher, Central Dysfunction?

Objective Persistent postural-perceptual dizziness (PPPD) is the most common vestibular disorder in the age group between 30 and 50 years. It is considered to be based on a multisensory maladjustment involving alterations of sensory response pattern including vestibular, visual and motion stimuli. Previous data supported a link between vestibular and pain mechanism. The aim of the study was to investigate whether other sensory inputs such as pain stimuli might be altered in terms of a more widespread central perception dysfunction in this disorder. Methods Nociceptive blink reflex was measured in 27 patients with PPPD and compared with 27 healthy, age and gender matched controls. The habituation of the R2 component of the blink reflex was evaluated as the percentage area-under-the curve (AUC) decrease in ten consecutive blocks of five averaged rectified responses. Additionally, clinical characteristics were evaluated. Results In patients with PPPD a lack of habituation was observed compared to healthy controls. Relative AUC decreased between the first and the tenth block by 19.48% in PPPD patients and by 31.63% (p = 0.035) in healthy controls. There was no correlation between clinical data (course of disease, comorbid depression, medication, trigger factors) or electrophysiological data (perception threshold, pain threshold, stimulus intensity) and habituation pattern. No trigeminal sensitization in terms of facilitation of absolute values could be detected. Conclusion Our study results supports the hypothesis of the multisensory dimension of impaired sensory processing in patients with PPPD extends beyond vestibular/visual motion stimuli and reflexive postural/oculomotor control mechanisms to other sensory inputs such as pain perception in terms of a more generalized disturbed habituation pattern.

Lateralized central facilitation of trigeminal nociception in cluster headache

Objective: To investigate whether central facilitation of trigeminal pain processing is part of the pathophysiology of cluster headache (CH). Methods: Sixty-six patients with CH (18 episodic CH inside bout, 28 episodic CH outside bout, 20 chronic CH) according to the International Classification of Headache Disorders–II classification, as well as 30 healthy controls, were investigated in a case-control study using simultaneous recordings of the nociceptive blink reflex (nBR) and pain-related evoked potentials (PREP) following nociceptive electrical stimulation on both sides of the forehead (V1). Results: nBR latency ratio (headache side/nonheadache side) was decreased in all CH patients independent from CH subtype compared with healthy controls indicating central facilitation at brainstem level. Area under the curve ratio was increased in patients with episodic CH inside bout only. PREP showed decreased N2 latency ratio in patients with chronic CH indicating central facilitation at supraspinal (thalamic or cortical) level. Conclusions: Asymmetric facilitation of trigeminal nociceptive processing predominantly on brainstem level was detected in patients with CH. This alteration is most pronounced in the acute pain phase of the disease, but appears to persist in remission periods. Only chronic CH patients show additional changes of PREP prompting to supraspinal changes of pain processing related to the chronic state of disease in regard to neuronal plasticity, which exceeds changes observed in episodic CH.