Transcutaneous Supraorbital Stimulation as a Preventive Treatment for Chronic Migraine: A Prospective, Open-Label Study.

BACKGROUND AND OBJECTIVE: Successful preventive treatment in chronic migraine (CM) remains an unmet need in some cases, and new therapeutic strategies are emerging. We aimed to test the effect of noninvasive, transcutaneous supraorbital nerve stimulation (tSNS) in a group of patients with CM. PATIENTS AND METHODS: This was an open label, quasi-experimental design. Twenty-five CM patients were recruited from two hospital headache clinics. After a one-month baseline period, monthly visits were scheduled during three months. Headache occurrence, its intensity, and symptomatic medication intake were recorded through a diary kept by each patient. Both a per-protocol analysis and an intention-to-treat analysis were performed for the main outcome measures. RESULTS: Twenty-one and 24 patients were included in the per-protocol and the intention-to-treat analyses, respectively. In the per-protocol analysis, a significant four-day decrease in the mean monthly days with moderate or severe headache was observed from baseline to the end of the study (t test, P = 0.0163), and there was a nonsignificant reduction of 2.95 in the mean monthly total headache days. In the intention-to-treat analysis, a nonsignificant 3.37 reduction in the mean monthly days with moderate or severe headache was observed for the same period, and there was a significant 2.75 reduction in the mean monthly days with any headache (t test, P = 0.016). CONCLUSIONS: tSNS could hold preventive properties in the treatment of CM, but the effect may be either mild or controversial. Double blind, sham-controlled studies are essential to confirm these findings and to outline their clinical relevance in the CM therapeutic scenario.

Paroxysmal pressing headache: A new short-lasting headache.

INTRODUCTION: In this report we describe a series of patients with a previously undescribed headache. METHODS: Over a 4-year period, we recruited 14 patients with a distinctive type of head pain of unknown cause that did not meet diagnostic criteria for other primary headaches. RESULTS: Nine women and five men with a mean age of 49.6 years (standard deviation, 17.8) presented with spontaneous headache attacks lasting 2-15 minutes. In each attack, the pain was localized to a region of one side of the head. Pain location varied between episodes in 12 patients. Pain quality was pressing, and pain intensity was mild to severe. There were no accompanying symptoms. Physical examination and all ancillary tests were unremarkable. Among seven patients who tried pharmacological treatments, one responded to antidepressants, another to indomethacin and three to other nonsteroidal anti-inflammatory drugs or simple analgesics. CONCLUSIONS: Paroxysmal pressing headache may be a new headache syndrome marked by short duration of the pain and shifting location.

Supratrochlear Neuralgia: A Prospective Case Series of 15 Patients.

OBJECTIVE: The aim of this study was to describe clinical features unique to supratrochlear neuralgia. BACKGROUND: The supratrochlear nerve supplies the medial aspect of the forehead. Due to the intricate relationship between supraorbital and supratrochlear nerves, neuralgic pain in this region has been traditionally attributed to supraorbital neuralgia. No cases of supratrochlear neuralgia have been reported so far. METHODS: From 2009 through 2016, we prospectively recruited patients with pain confined to the territory of the supratrochlear nerve. RESULTS: Fifteen patients (13 women, 2 men; mean age 51.4 years, standard deviation 14.9) presented with pain in the lower paramedian forehead, extending to the eyebrow in two patients and to the internal angle of the orbit in another. Pain was unilateral in 11 patients (six on the right, five on the left), and bilateral in four. Six patients had continuous pain and nine described intermittent pain. Palpation of the supratrochlear nerve at the medial third of the supraorbital rim resulted in hypersensitivity in all cases. All but one patient exhibited sensory disturbances within the painful area. Fourteen patients underwent anesthetic blockades of the supratrochlear nerve, with immediate relief in all cases and long-term remission in three. Six of them had received unsuccessful anesthetic blocks of the supraorbital nerve. Five patients were treated successfully with oral drugs and one patient was treated with radiofrequency. CONCLUSIONS: Supratrochlear neuralgia is an uncommon disorder causing pain in the medial region of the forehead. It may be differentiated from supraorbital neuralgia and other similar headaches and neuralgias based on the topography of the pain and the response to anesthetic blockade.

Botulinum Neurotoxin Type-A for the Treatment of Atypical Odontalgia.

OBJECTIVE: Atypical odontalgia (AO), a subform of persistent idiopathic facial pain, is defined as a continuous toothache in which a thorough examination reveals no dental pathology. AO is believed to be a neuropathic condition, given that some cases are preceded by dental procedures. Different topical and systemic medications have been used for the treatment of AO, but their effect is often unsatisfactory. The authors aimed to assess the effect and safety of botulinum neurotoxin type-A (BoNTA) in a series of patients with AO. METHODS: Four patients with refractory AO (2 males and 2 females, aged 31-72) were treated with local injections of BoNTA to the painful area. BoNTA was injected at various sites into the gums, and two patients had additional injections in the hard palate or the upper lip. The total dose of BoNTA for each procedure was 15-30 U, and the total number of injection points was 6-12. The follow-up ranged from 6 to 20 months. Two patients received two cycles of BoNTA, while the remaining patients received three and five cycles each, respectively. RESULTS: All patients obtained significant relief with complete or almost complete reduction of pain. The analgesic effect was apparent after a latency period of 3-14 days, and the effect persisted for 2-6 months. There were no adverse events reported from any of the interventions. CONCLUSIONS: The responses to BoNTA injections in this series agree with those previously observed in neuropathic pain. BoNTA injections may be a safe and effective option for the treatment of AO.

Identification of Subgroups of Women with Carpal Tunnel Syndrome with Central Sensitization.

OBJECTIVE: Identification of subjects with different sensitization mechanisms can help to identify better therapeutic strategies for carpal tunnel syndrome (CTS). The aim of the current study was to identify subgroups of women with CTS with different levels of sensitization. METHODS: A total of 223 women with CTS were recruited. Self-reported variables included pain intensity, function, disability, and depression. Pressure pain thresholds (PPT) were assessed bilaterally over median, ulnar, and radial nerves, C5-C6 joint, carpal tunnel, and tibialis anterior to assess widespread pressure pain hyperalgesia. Heat (HPT) and cold (CPT) pain thresholds were also bilaterally assessed over the carpal tunnel and the thenar eminence to determine thermal pain hyperalgesia. Pinch grip force between the thumb and the remaining fingers was calculated to determine motor assessment. Subgroups were determined according to the status on a previous clinical prediction rule: PPT over the affected C5-C6 joint < 137 kPa, HPT on affected carpal tunnel <39.6ºC, and general health >66 points. RESULTS: The ANOVA showed that women within group 1 (positive rule, n = 60) exhibited bilateral widespread pressure hyperalgesia (P < 0.001) and bilateral thermal thresholds (P < 0.001) than those within group 2 (negative rule, n = 162). Women in group 1 also exhibited higher depression than those in group 2 (P = 0.023). No differences in self-reported variables were observed. CONCLUSION: This study showed that a clinical prediction rule originally developed for identifying women with CTS who are likely to respond favorably to manual physical therapy was able to identify women exhibiting higher widespread pressure hyper-sensitivity and thermal hyperalgesia. This subgroup of women with CTS exhibiting higher sensitization may need specific therapeutic programs.

Epicrania Fugax.

Epicrania fugax (EF) is a primary headache of recent description. EF essentially consists of brief paroxysms of pain describing a linear or zigzag trajectory across the surface of one hemicranium, commencing and terminating in the territories of different nerves. The pain of forward EF originates in a particular area of the occipital, parietal or temporal regions and moves anteriorly, whereas the pain of backward EF originates in the frontal area, the eye or the nose and moves posteriorly. Some patients have ocular or nasal autonomic accompaniments, and some have triggers. Between attacks, many patients have continuous or intermittent pain and/or tenderness at the stemming area. Pain frequency is extremely variable and some patients have spontaneous remissions. Preventive therapy is required when the paroxysms are frequent and non-remitting. Neuromodulators, indomethacin, amitryptiline, nerve anesthetic blockades, and trochlear steroid injections have been used in different cases, with partial or complete response.

Infratrochlear neuralgia.

INTRODUCTION: The infratrochlear nerve supplies the medial aspect of the upper eyelid, the superolateral aspect of the nose and the lacrimal caruncle. This nerve may contribute to the pain stemming from the trochlea, but infratrochlear neuralgia has not been identified as a specific cause of pain. METHODS: Over a 10-year period we have been recruiting patients with pain in the internal angle of the orbit that did not show features of trochlear pain. RESULTS: Seven patients (six female, one male; mean age, 46.1 ± 18.9) presented with pain in the territory of the infratrochlear nerve. The pain appeared in the internal angle of the orbit and upper eyelid (n = 3), the superolateral aspect of the nose (n = 3), or the lacrimal caruncle (n = 1). All patients had a paroxysmal pain, with the attacks lasting five to 30 seconds. Pain attacks were mostly spontaneous, but two patients had triggers. Between attacks, all patients had local allodynia. Pain did not increase with vertical eye movements. Six patients were treated with gabapentin with complete response, and one patient experienced long-lasting relief with an anesthetic blockade of the infratrochlear nerve. CONCLUSION: Infratrochlear neuralgia should be considered as a possible cause of pain in the internal angle of the orbit.

Idiopathic Ophthalmodynia and Idiopathic Rhinalgia: A Prospective Series of 16 New Cases.

BACKGROUND: Idiopathic ophthalmodynia and idiopathic rhinalgia were described a few years ago. These conditions seem specific pain syndromes with a distinctive location in the eye or in the nose. We aimed to present a new prospective series in order to verify the consistency of these syndromes. METHODS: We performed a descriptive study of all patients referred to our regional neurologic clinics from 2010 to 2014 because of facial pain exclusively felt in the eye or in the nose fulfilling the proposed diagnostic criteria for idiopathic ophthalmodynia and idiopathic rhinalgia. RESULTS: There were 9 patients with idiopathic ophthalmodynia and 7 patients with idiopathic rhinalgia, with a clear female preponderance, and a mean age at onset in the fifth decade. The pain was usually moderate and the temporal pattern was generally chronic. Only one patient reported accompaniments (hypersensitivity to the light and to the flow of air in the symptomatic eye). Preventive treatment with amitriptyline, pregabalin, or gabapentin was partially or totally effective. CONCLUSIONS: The clinical features of this new series parallels those of the original description, thus indicating that both idiopathic ophthalmodynia and idiopathic rhinalgia have clear-cut clinical pictures with excellent consistency both inter- and intra-individually.

Linear interictal pain in Epicrania Fugax.

Epicrania Fugax is a paroxysmal, short-lasting, head pain moving across one hemicranium, describing a linear or zag trajectory, starting and ending in territories of different nerves. Between attacks, patients are usually free of symptoms. We describe an Epicrania Fugax patient complaining of interictal pain. The interictal pain was line-shaped and extended across the usual starting and ending points of the typical Epicrania Fugax paroxysms. Although rarely encountered, persistent linear pain may be a feature of Epicrania Fugax.

Activation in the hypothalamic-pituitary-adrenocortical axis and sympathetic nervous system in women with carpal tunnel syndrome.

OBJECTIVE: The aim of this study is to investigate the differences in salivary cortisol (hypothalamic-pituitary-adrenocortical [HPA] axis), α-amylase activity (sympathetic nervous system [SNS]), and immunoglobulin A (IgA; immune system) concentrations between women with carpal tunnel syndrome (CTS) and healthy women. DESIGN: A cross-sectional study. SETTING: Activation of HPA, SNS, and immune system in CTS has not been clearly determined. PATIENTS: One hundred two women (age: 45 ± 7 years) with electrodiagnostic and clinical diagnosis of CTS and 102 matched healthy women. OUTCOME MEASURES: The intensity of the pain was assessed with a Numerical Pain Rating Scale (0-10), and disability was determined with Boston Carpal Tunnel Questionnaire. Salivary cortisol concentration, α-amylase activity, salivary flow rate, and IgA concentration were collected from nonstimulated saliva. RESULTS: Women with CTS exhibited lower salivary flow rate (P < 0.001) and higher α-amylase activity (P < 0.01) than controls. No significant differences for cortisol and IgA concentrations (P > 0.2) were found between groups as a total. Women with severe CTS exhibited lower salivary flow rate (P < 0.001), higher α-amylase activity (P = 0.002), and higher cortisol concentration (P = 0.03) than healthy women and than those with minimal/moderate CTS (P < 0.05). Within women with CTS, significant positive associations between α-amylase activity and the intensity of pain were found: the highest the level of pain, the higher the α-amylase activity, i.e., higher SNS activation. CONCLUSIONS: These results suggest that women with severe CTS exhibit changes in activation in the HPA axis and SNS but not in the humoral immune system. Activation of the SNS was associated with the intensity of pain. Future studies are needed to elucidate the direction of this relationship.

Refractory primary and secondary headache disorders that dramatically responded to combined treatment of ultrasound-guided percutaneous suprazygomatic pterygopalatine ganglion blocks and non-invasive vagus nerve stimulation: a case series.

In 1981, Devoghel achieved an 85.6% success rate in treating patients with treatment-refractory cluster headaches with alcoholization of the pterygopalatine ganglion (PPG) via the percutaneous suprazygomatic approach. Devoghel's study led to the theory that interrupting the parasympathetic pathway by blocking its transduction at the PPG could prevent or treat symptoms related to primary headache disorders (PHDs). Furthermore, non-invasive vagus nerve stimulation (nVNS) has proven to treat PHDs and has been approved by national regulatory bodies to treat, among others, cluster headaches and migraines.In this case series, nine desperate patients who presented with 11 longstanding treatment-refractory primary headache disorders and epidural blood patch-resistant postdural puncture headache (PDPH) received ultrasound-guided percutaneous suprazygomatic pterygopalatine ganglion blocks (PPGB), and seven also received nVNS. The patients were randomly selected and were not part of a research study. They experienced dramatic, immediate, satisfactory, and apparently lasting symptom resolution (at the time of the writing of this report). The report provides the case descriptions, briefly reviews the trigeminovascular and neurogenic inflammatory theories of the pathophysiology, outlines aspects of these PPGB and nVNS interventions, and argues for adopting this treatment regime as a first-line or second-line treatment rather than desperate last-line treatment of PDPH and PHDs.

Lacrimal neuralgia: so far, a missing cranial neuralgia.

BACKGROUND: The lacrimal nerve supplies the lacrimal gland, the lateral upper eyelid, and a small cutaneous area adjacent to the external CANTHUS . First division trigeminal neuralgia, supraorbital/supratrochlear neuralgia, and infraorbital neuralgia have been acknowledged as neuralgic causes of pain in the forehead and periorbit. However, the lacrimal nerve has never been identified as a source of facial pain. Here we report two cases of lacrimal neuralgia. CASE REPORTS: A 66-year-old woman had continuous pain in the lateral aspect of her left superior eyelid and an adjacent area of the temple since age 64. A 33-year-old woman suffered from continuous pain in a small area next to the lateral CANTHUS of her left eye since age 25. In both patients the superoexternal edge of the orbit was tender. In addition, sensory dysfunction could be demonstrated within the painful area. Anaesthetic blockades of the lacrimal nerve with lidocaine 2% resulted in complete but short-lasting relief. Pregabalin provided a complete response in the first patient. The second patient was refractory to various oral and topical drugs and different radiofrequency procedures, but she eventually obtained partial relief with pregabalin. CONCLUSIONS: Lacrimal neuralgia should be considered among the neuralgic causes of orbital and periorbital pain.

Unilateral nasal pain with migraine features.

BACKGROUND: Migraine attacks exclusively felt in the face are very rare, the pain involving the territories supplied by the second and third branches of the trigeminal nerve. CASES: Two patients suffering from heminasal pain attacks accompanied with typical migrainous features and responsive to oral or intranasal triptans - but not to intranasal lidocaine or oxymetazoline. In one patient, the attacks could be precipitated upon slight touching on the tip of the nose, in the other attacks were preceded by the nasal sensation typically heralding sneezing. DISCUSSION: Migraine pain mostly develops within the innervation territory of the first branch of the trigeminal nerve, which includes the nose. Therefore, episodes of unilateral nasal pain with migrainous features could be considered a migraine with unusual topography (nasal migraine). Painful nasal attacks occasionally preceded by stimulation of trigeminal afferents in the nose, could be conceived of as migraine-tic syndrome.

The usual treatment of trigeminal autonomic cephalalgias.

Trigeminal autonomic cephalalgias include cluster headache, paroxysmal hemicrania, and short-lasting unilateral neuralgiform headache attacks with conjunctival injection, tearing, and rhinorrhea (SUNCT). Conventional pharmacological therapy can be successful in the majority of trigeminal autonomic cephalalgias patients. Most cluster headache attacks respond to 100% oxygen inhalation, or 6 mg subcutaneous sumatriptan. Nasal spray of sumatriptan (20 mg) or zolmitriptan (5 mg) are recommended as second choice. The bouts can be brought under control by a short course of corticosteroids (oral prednisone: 60-100 mg/day, or intravenous methylprednisolone: 250-500 mg/day, for 5 days, followed by tapering off the dosage), or by long-term prophylaxis with verapamil (at least 240 mg/day). Alternative long-term preventive medications include lithium carbonate (800-1600 mg/day), methylergonovine (0.4-1.2 mg/day), and topiramate (100-200 mg/day). As a rule, paroxysmal hemicrania responds to preventive treatment with indomethacin (75-150 mg/day). A short course of intravenous lidocaine (1-4 mg/kg/hour) can reduce the flow of attacks during exacerbations of SUNCT. Lamotrigine (100-300 mg/day) is the preventive drug of choice for SUNCT. Gabapentin (800-2700 mg/day), topiramate (50-300 mg/day), and carbamazepine (200-1600 mg/day) may be of help.

Effects of Non-Invasive Neuromodulation of the Vagus Nerve for the Management of Cluster Headache: A Systematic Review.

BACKGROUND: Cluster headache (CH) is a type of headache that has a global prevalence of 0.5-3/1000 people, provokes severe, strictly unilateral pain through the first branch of the trigeminal nerve, and is associated with observable autonomous responses. CH provokes intense pain and decreases quality of life. OBJECTIVE: In this study, we aimed to carry out a systematic review of the effectiveness of non-invasive neuromodulation of the vagus nerve in patients with cluster headaches, which was registered on PROSPERO No. CRD42021265126. METHODS: Six databases were used from their date of inception to February 2023 to obtain studies with the group intervention of non-invasive neuromodulation of the vagus nerve for cluster headache, with outcomes based on pain attacks, duration, and disabilities. Data on the subjects, group intervention, main outcomes, and results were collected by two authors. RESULTS: The search provided 1003 articles, with three clinical trials being eligible for inclusion in the review. The methodological quality scores ranged from 6 to 8 points (mean: 7.3, SD: 0.8) out of a maximum of 10 points. The post-treatment results showed some positive effects using n-VNS as a treatment for cluster headache, more specifically regarding cervical neuromodulation of the vagus nerve. CONCLUSIONS: The systematic review found moderate-to-high-quality evidence supporting that n-VNS and cervical n-VNS may have some positive effects at the end of the treatment being effective to relieve the frequency and intensity of cluster headaches. The poor quantity of studies available and the lack of homogeneity in the study protocols did not allow the pooling of data for a meta-analysis.

Path Analysis Models Integrating Psychological, Psycho-physical and Clinical Variables in Individuals With Tension-Type Headache.

Tension type headache (TTH) is a prevalent but poorly understood pain disease. Current understanding supports the presence of multiple associations underlying its pathogenesis. Our aim was to compare competing multivariate pathway models that explains the complexity of TTH. Headache features (intensity, frequency, or duration - headache diary), headache-related disability (Headache Disability Inventory-HDI), anxiety/depression (Hospital Anxiety and Depression Scale), sleep quality (Pittsburgh Sleep Quality Index), widespread pressure pain thresholds (PPTs) and trigger points (TrPs) were collected in 208 individuals with TTH. Four latent variables were formed from the observed variables - Distress (anxiety, depression), Disability (HDI subscales), Severity (headache features), and Sensitivity (all PPTs). Structural equation modelling (SEM) and Bayesian network (BN) analyses were used to build and compare a theoretical (modeltheory) and a data-driven (modelBN) latent variable model. The modelBN (root mean square error of approximation [RMSEA] = 0.035) provided a better statistical fit than modeltheory (RMSEA = 0.094). The only path common between modelbn and modeltheory was the influence of years with pain on TrPs. The modelBN revealed that the largest coefficient magnitudes were between the latent variables of Distress and Disability (ß=1.524, P = .006). Our theoretical model proposes a relationship whereby psycho-physical and psychological factors result in clinical features of headache and ultimately affect disability. Our data-driven model proposes a more complex relationship where poor sleep, psychological factors, and the number of years with pain takes more relevance at influencing disability. Our data-driven model could be leveraged in clinical trials investigating treatment approaches in TTH. PERSPECTIVE: A theoretical model proposes a relationship where psycho-physical and psychological factors result in clinical manifestations of headache and ultimately affect disability. A data-driven model proposes a more complex relationship where poor sleep, psychological factors, and number of years with pain takes more relevance at influencing disability.

Ultrasound-guided percutaneous electrical nerve stimulation versus surgery for women with unilateral carpal tunnel syndrome: A randomized parallel-group trial.

OBJECTIVE: The aim of this clinical trial was to compare the outcomes of the application of ultrasound-guided percutaneous nerve stimulation (PENS) targeting the median nerve versus surgery for improving pain and function in women with CTS. METHODS: In this randomized parallel-group trial (ClinicalTrials.gov, NCT04246216), 70 women with CTS were randomly allocated to either PENS (n = 35) or surgery (n = 35) group. Hand pain intensity (mean pain and the worst pain experienced) was the primary outcome. Functional status and symptoms severity (Boston Carpal Tunnel Questionnaire, BCTQ) and self-perceived improvement (Global Rating of Change, GROC) were the secondary outcomes. Outcomes were assessed at baseline and 1, 3, 6 and 12 months after each intervention. Analysis was performed with intention to treat with mixed ANCOVAs adjusted for baseline outcomes. RESULTS: Analyses showed an adjusted advantage for PENS at 1 (Δ -2.0, 95% CI -2.9 to -1.1) and 3 (Δ -1.4, 95% CI -2.3 to -0.5) months for mean pain, at 1 (Δ -2.2, 95% CI -3.3 to -1.1), 3 (Δ -1.75, 95% CI -2.9 to -0.6) and 6 (Δ -1.7, 95% CI -2.8 to -0.6) months in the worst pain intensity, and at 1 (Δ -0.95, 95% CI -1.1 to -0.8), 3 (Δ -0.55, 95% CI -0.8 to -0.3) and 6 (Δ -0.4, 95% CI -0.6 to -0.8) months in function. Both groups exhibited similar changes in symptom severity. Both groups reported similar improvement at 12 months in all outcomes. Symptoms and function improved in both groups, with PENS leading to better short-term outcomes than surgery. CONCLUSION: This clinical trial confirms that PENS applied with current understanding of pain mechanisms in CTS is as useful as surgery in women with CTS without denervation. The potential placebo effect of both interventions should not be ignored. SIGNIFICANCE: The application of percutaneous nerve stimulation was more effective at short-term, but similar effective at mid and long-term, than surgery in women with carpal tunnel syndrome.

Primary continuous unilateral headaches: a nosologic model for hemicrania continua.

BACKGROUND: Hemicrania continua was originally described as a strictly unilateral, continuous headache with an absolute response to indomethacin. Recognition of an increasing number of patients with the same clinical features except for a lack of response to indomethacin has generated controversy about whether the responsive/non-responsive phenotypes belong to the same disorder. DISCUSSION: We suggest that the non-responsive phenotype should be differentiated from the original concept of hemicrania continua, because it probably indicates a separate type of headache of undetermined nature, i.e. hemicrania incerta. However, differentiating hemicrania incerta from hemicrania continua does not imply that the two headaches are unrelated. Both hemicranias may outline a continuum, giving rise to a broader diagnostic field. CONCLUSION: There seems to be a syndrome of 'primary continuous unilateral headache' with at least two distinctive categories: hemicrania continua and hemicrania incerta, which are differentiated by their respective response to indomethacin. This division means plurality but adds precision, and allows a clear-cut diagnosis of some controversial cases.

Nummular headache update.

Nummular headache is characterized by head pain exclusively felt in a rounded or elliptical area, typically 1 to 6 cm in diameter. The pain remains confined to the same symptomatic area, which does not change in shape or size with time. The symptomatic area may be localized in any part of the head but mostly in the parietal region. Rarely, the disorder may be multifocal, each symptomatic area keeping all the characteristics of nummular headache. The pain is generally mild or moderate, commonly described as oppressive or stabbing, and lasting minutes, hours, or days, with a remitting or unremitting pattern. Superimposed on the baseline pain, there may be spontaneous or triggered exacerbations. During and between symptomatic periods, the affected area may show variable combinations of hypoesthesia, dysesthesia, paresthesia, tenderness, and trophic changes. Nummular headache emerges as a primary disorder with a clear-cut clinical picture developed in a unique topography.

Network Analysis Reveals That Headache-Related, Psychological and Psycho-Physical Outcomes Represent Different Aspects in Women with Migraine.

Evidence supports that migraine is a complex pain condition with different underlying mechanisms. We aimed to quantify potential associations between demographic, migraine-related, and psychophysical and psychophysical variables in women with migraine. Demographic (age, height, and weight), migraine-related (intensity, frequency, and duration), related-disability (Migraine Disability Assessment Scale, Headache Disability Inventory), psychological (Hospital Anxiety and Depression Scale), and psycho-physical (pressure pain thresholds -PPTs-) variables were collected from a sample of 74 women suffering from migraine. We calculated adjusted correlations between the variables by using a network analysis. Additionally, we also calculated centrality indices to identify the connectivity among the variables within the network and the relevance of each variable in the network. Multiple positive correlations (ρ) between PPTs were observed ranging from 0.1654 (C5-C6 and tibialis anterior) to 0.40 (hand and temporalis muscle). The strongest associations within the network were those between migraine attack frequency and diagnosis of chronic migraine (ρ = 0.634) and between the HDI-E and HDI-P (ρ = 0.545). The node with the highest strength and betweenness centrality was PPT at the second metacarpal, whereas the node with the highest harmonic centrality was PPT at the tibialis anterior muscle. This is the first study applying a network analysis to understand the underlying mechanisms in migraine. The identified network revealed that a model where each subgroup of migraine-related, psychological, and psycho-physical variables showed no interaction between each variable. Current findings could have clinical implications for developing multimodal treatments targeting the identified mechanisms.