Laura H Schulte

Efficacy of interventions used by physiotherapists for patients with headache and migraine-systematic review and meta-analysis.

Aim We aimed to conduct a systematic review evaluating the effectiveness of interventions used by physiotherapists on the intensity, frequency and duration of migraine, tension-type (TTH) and cervicogenic headache (CGH). Methods We performed a systematic search of electronic databases and a hand search for controlled trials. A risk of bias analysis was conducted using the Cochrane risk of bias tool (RoB). Meta-analyses present the combined mean effects; sensitivity analyses evaluate the influence of methodological quality. Results Of 77 eligible trials, 26 were included in the RoB assessment. Twenty trials were included in meta-analyses. Nineteen out of 26 trials had a high RoB in >1 domain. Meta-analyses of all trials indicated a reduction of TTH (p < 0.0001; mean reduction −1.11 on a 0–10 visual analog scale (VAS); 95% CI −1.64 to −0.57) and CGH (p = 0.0002; mean reduction −2.52 on a 0–10 VAS; 95% CI −3.86 to −1.19) pain intensity, CGH frequency (p < 0.00001; mean reduction −1.34 days per month; 95% CI −1.40 to −1.28), and migraine (p = 0.0001; mean reduction −22.39 hours without relief; 95% CI −33.90 to −10.88) and CGH (p < 0.00001; mean reduction −1.68 hours per day; 95% CI −2.09 to −1.26) duration. Excluding high RoB trials increased the effect sizes and reached additional statistical significance for migraine pain intensity (p < 0.00001; mean reduction −1.94 on a 0–10 VAS; 95% CI −2.61 to −1.27) and frequency (p < 0.00001; mean reduction −9.07 days per month; 95% CI −9.52 to −8.62). Discussion Results suggest a statistically significant reduction in the intensity, frequency and duration of migraine, TTH and CGH. Pain reduction and reduction in CGH frequency do not reach clinically relevant effect sizes. Small sample sizes, inadequate use of headache classification, and other methodological shortcomings reduce the confidence in these results. Methodologically sound, randomized controlled trials with adequate sample sizes are required to provide information on whether and which physiotherapy approach is effective. According to Grading of Recommendations Assessment, Development and Evaluation (GRADE), the current level of evidence is low.

Photo-, osmo- and phonophobia in the premonitory phase of migraine: mistaking symptoms for triggers?

BackgroundCertain environmental stimuli are frequently reported as typical triggers of migraine pain. Whether these so-called triggers are independent precipitators of migraine pain or mere symptoms of the premonitory phase of migraine remains to be elucidated.MethodsIn this retrospective cohort study of 1010 migraine patients of a tertiary headache center we assessed the frequency of common trigger factors, premonitory symptoms and accompanying symptoms as well as basic headache characteristics and demographic data.ResultsPremonitory symptoms with an onset of 2 or more hours prior to the headache were present in 38.9% of migraine patients, the most frequent being a tense neck, phonophobia and difficulty concentrating. There was a clear overlap of certain trigger factors and the presence of corresponding premonitory symptoms: flickering or bright light as a trigger was associated with higher frequency of photophobia in the premonitory phase. The same applied to the presence of food craving and osmophobia in the premonitory phase and certain foods or odours as trigger factors.ConclusionsOur data thus support the view that commonly reported trigger factors of migraine are not so much independent precipitators of migraine pain, but that they are most likely just misinterpreted results of enhanced attention to certain stimuli mediated by typical premonitory symptoms of migraine pain.

Hypothalamus as a mediator of chronic migraine Evidence from high-resolution fMRI

Objective: To identify pathophysiologic mechanisms of migraine chronification using a recently standardized protocol for high-resolution brainstem imaging of trigeminal nociceptive stimulation. Methods: Eighteen episodic migraineurs (EMs), 17 chronic migraineurs (CMs), and 19 healthy controls (HCs) underwent painful ammonia stimulation of the left nostril in a 3T MRI scanner. Functional images were acquired with a brainstem-optimized protocol for high-resolution echo-planar imaging. Results: We detected a significantly stronger activation of the anterior right hypothalamus in CMs compared to HCs. To exclude the headache as a prime mediator of the hypothalamic activations, we compared all migraineurs with headaches (EMs and CMs) with all migraineurs without headaches (EMs and CMs) and HCs in a second analysis and found a more posterior region of the hypothalamus to be more activated bilaterally during headaches. Conclusions: Our data corroborate the fact that the hypothalamus plays a crucial role in the pathophysiology of migraine chronification and acute pain stage of migraineurs. While the more posterior part of the hypothalamus seems to be important for the acute pain stage, the more anterior part seems to play an important role in attack generation and migraine chronification.

Migraine trait symptoms in migraine with and without aura

Objectives: The aim of the study was to determine whether various transient sensory and neuropsychological symptoms (SNS) were associated with migraine using a custom questionnaire. Methods: In this hypothesis-generating case-control study, the frequencies of transient SNS in 219 patients with migraine (149 without aura and 70 with aura) were compared with 161 age- and sex-matched healthy controls using a custom questionnaire. Patients from a tertiary academic headache center in Hamburg were contacted by regular mail. Healthy controls without a history of migraine were recruited by means of a screening questionnaire and consecutively approached by e-mail. Results: The presence of both migraine and aura was associated with significantly higher frequencies of autokinesis, metamorphopsia, dyschromatopsia, cinematographic vision, illusionary visual spread, and synesthesia (for all comparisons: corrected p < 0.05). Double vision, inverted 2- and 3-dimensional vision, and altered perception of body weight and size were found more often in patients with migraine without aura than in those with aura. In contrast, aura was associated with the occurrence of visual splitting and corona phenomenon (for all comparisons: corrected p < 0.05). No relevant association with migraine was found for micropsia and macropsia, teleopsia and pelopsia, inverted vision, out-of-body experience, Doppelgänger phenomenon, complex visual hallucinations, and altered perception of body position in space. Conclusions: The observed SNS seem to belong to a physiologic spectrum of multisensory phenomena. Some of these phenomena were significantly accentuated in patients with migraine and may therefore be termed migraine trait symptoms. However, these results will have to be confirmed in a prospective study with face-to-face interviews.

Indomethacin-induced de novo headache in hemicrania continua—fighting fire with fire?:

Introduction The response to indomethacin is an important feature for the diagnosis of hemicrania continua. Case description We report the case of a 34-year-old female patient with a one-year history of strictly unilateral continuous headache with accompanying ipsilateral autonomic symptoms. As diagnostic testing was unremarkable, hemicrania continua was suspected. A dose of 150 mg of indomethacin/day reduced the headache by 80%. Although an increase to 225 mg/day led to a further reduction of headaches, a new onset of moderate to severe pulsating migrainous bilateral headache developed. Discussion As shown in older studies, indomethacin can induce de novo headaches in a presumably dose-related fashion although the exact mechanism in uncertain. A treatable secondary origin of the indomethacin-induced headaches in patients with hemicrania continua or paroxysmal hemicrania (such as reversible cerebral vasoconstriction syndrome or aseptic meningitis) should be considered and excluded by further diagnostic testing if headaches persist after discontinuation of indomethacin.

Oxygen treatment is effective in migraine with autonomic symptoms.

Introduction While inhalation of high-flow 100% oxygen is highly effective in cluster headache, studies on its efficacy in migraine are sparse and controversial. Case We report the case of a 22-year-old patient with an eight-year history of strictly unilateral migraine without aura but cranial autonomic symptoms. She repeatedly responded completely to inhalation of high-flow pure oxygen within 15 min but suffered from recurrence of attacks within 30 min after discontinuation. Discussion In line with experimental animal studies, this case suggests a clinically relevant efficacy of inhaled oxygen in patients with migraine with accompanying cranial autonomic symptoms.

Linear and inverted U-shaped dose-response functions describe estrogen effects on hippocampal activity in young women

In animals, 17-beta-estradiol (E2) enhances hippocampal plasticity in a dose-dependent, monotonically increasing manner, but this relationship can also exhibit an inverted U-shaped function. To investigate E2’s dose-response function in the human hippocampus, we pharmacologically increased E2 levels in 125 naturally cycling women (who were in their low-hormone menstruation phase) to physiological (equivalent to menstrual cycle peak) and supraphysiological (equivalent to levels during early pregnancy) concentrations in a placebo-controlled design. Twenty-four hours after first E2 intake, we measured brain activity during encoding of neutral and negative pictures and then tested recognition memory 24 h after encoding. Here we report that E2 exhibits both a monotonically increasing relationship with hippocampal activity as well as an inverted U-shaped relationship, depending on the hippocampal region. Hippocampal activity exhibiting a U-shaped relationship inflects at supraphysiological E2 levels, suggesting that while E2 within physiological ranges stimulates hippocampal activity, supraphysiological ranges show opposite effects.While estrogen is known to change hippocampal activity in animals, it is not known if this effect extends to humans. Here, authors vary the doses of estrogen in young women and show that the effects on hippocampal activity can be described by linear and inverted-U shaped dose-response functions.

Visual stimulation leads to activation of the nociceptive trigeminal nucleus in chronic migraine

Objective The visual system has often been described to be sensitized in migraineurs, with light being perceived as aversive or even painful. One possible explanation for this altered perception is crosslinks between the visual and the trigeminonociceptive system. Visual stimulation in chronic migraineurs on the level of the brainstem might lead to enhanced activity within the spinal trigeminal nucleus (sTN) as the main site of trigeminal pain processing within this area. Methods Eighteen episodic migraineurs (EM), 17 chronic migraineurs (CM), and 19 healthy controls (HC) underwent one session of high-resolution brainstem imaging during which a rotating checkerboard was presented repeatedly as a visual stimulus. Data were analyzed using SPM12 and MATLAB with the classic first-level–second-level approach of SPM. Analyses of variance were used for group comparisons. Results CM showed enhanced activation within the sTN as compared to HC. In addition, we observed enhanced activity within the right superior colliculus in CM as compared to HC. When comparing all migraineurs with headaches during scanning with all migraineurs without headaches during scanning and HC, we also found the sTN to be more strongly activated during headaches. Conclusion Our data provide evidence for the existence of visual–nociceptive integration on brainstem level in chronic migraineurs.

EHMTI-0154. Brainstem mechanisms of trigeminal nociception: an fMRI study at 3T

The brainstem is the major site of trigeminal pain processing and modulation and plays a key role in the pathophysiology of various headache disorders. However, comprehensive human imaging studies on function and activity of brainstem areas following trigeminal nociceptive stimulation are scarce.