Visual inspection versus spectrophotometry for xanthochromia detection in patients with sudden onset severe headache-A diagnostic accuracy study.

OBJECTIVE: There is still disagreement about whether to routinely use spectrophotometry to detect xanthochromia in cerebrospinal fluid (CSF) or whether visual inspection is adequate. We aimed to evaluate the diagnostic accuracy of these methods in detecting an aneurysmal subarachnoid hemorrhage in patients with sudden onset severe headache. BACKGROUND: When a patient presents to the emergency department with a headache for which there is suspicion of a subarachnoid hemorrhage, the gold standard to rule this out is to perform a CSF analysis for xanthochromia with or without spectrophotometry if the cranial non-contrast computed tomography (CT) upon admission is negative. METHODS: Having applied the gold standard, we retrospectively included patients with acute headache who underwent both CT scan and CSF spectrophotometry at our hospital in the period 2002-2020. Patients were excluded if the cranial CT was interpreted as positive, there was a bloody CSF, or if visual assessment data of the CSF was unavailable. We scrutinized the patients' medical records and evaluated the benefit of spectrophotometry compared to visual inspection. The net bilirubin absorbance cut-off for support of subarachnoid hemorrhage was set at >0.007 absorbance units. The spectrophotometry was also considered positive if the net bilirubin absorbance was ≤0.007 and net oxyhemoglobin absorbance was ≥0.1 absorbance units. We calculated and compared the sensitivity and specificity of CSF spectrophotometry and visual inspection of the CSF. RESULTS: In total, 769 patients, with a mean age of 42.3 ± (standard deviation [SD] = 17.3) years, were included. The headache onset was classified as a thunderclap headache in 41.5%, and 4.7% had a sudden loss of consciousness. Fifteen patients (2%) were finally diagnosed with a subarachnoid hemorrhage, six (0.8%) had an aneurysmal subarachnoid hemorrhage, seven (0.9%) had a perimesencephalic hemorrhage, one (0.1%) had a cortical cerebral sinus venous thrombosis, and one (0.1%) had a spinal epidural hematoma. Four patients (0.5%) had a subarachnoid hemorrhage that was not detected by visual inspection, and two were caused by an aneurysmal rupture. One of these two patients died just before intervention, and the other underwent coiling for an anterior communicating aneurysm. The number needed for lumbar puncture to detect a subarachnoid hemorrhage was 51, but 128 to detect an aneurysmal hemorrhage. The corresponding numbers needed for CSF spectrophotometric analysis were 192 and 385, respectively. Spectrophotometry was positive in 31 patients (4.0%), of whom 18 (2.3%) also had visually detected xanthochromia (11 true positive). The mean net bilirubin absorbance in the 13 samples with visually clear CSF was 0.0111 ± (SD = 0.0103) absorbance units, compared to 0.0017 ± (SD = 0.0013) in the CSF with negative spectrophotometry. The corresponding figures for net oxyhemoglobin absorbance were 0.0391 ± (SD = 0.0522) versus 0.0057 ± (SD = 0.0081). The sensitivity of spectrophotometric xanthochromia detection was 100% (95% confidence interval [CI], 78-100), compared to 73% (95% CI, 45-92) for visual xanthochromia detection. The specificity of spectrophotometric xanthochromia detection was 98% (95% CI, 97-99) compared to 99% (95% CI, 98-100) for visual xanthochromia detection. Both methods had high negative predictive values: 100% (95% CI, 99.5-100) versus 99.5% (95% CI, 98.6-99.9), respectively. CONCLUSIONS: Both visual inspection and spectrophotometry have high diagnostic accuracy for detecting CSF xanthochromia, but the lower sensitivity of visual assessment makes it unreliable, and we recommend the use of spectrophotometry in clinical practice.

Room tilt illusion and subclavian steal - a case report.

BACKGROUND: Room tilt illusion (RTI) is a rare symptom of higher vestibular dysfunction, consisting of a transient vertical rotation of the visual scene in the sagittal or coronal plane, most often 90o or 180o, without any alteration in shape, size and color of objects. CASE PRESENTATION: A 63-year-old woman with a history of hypertension and chronic obstructive pulmonary disease went through an uncomplicated aortobifemoral graft surgery due to aortoiliac occlusive disease. Post-operatively she experienced five episodes, lasting from 10 to 30 min, with RTI; 90o forward rotation of the visual scene in the sagittal plane. Work-up revealed subclavian steal grade 3, and transient ischemia of the central vestibular system of the brainstem was the presumed mechanism. CONCLUSION: The course of episodic RTIs is often benign, but RTI may represent ischemia in the posterior cerebral circulation. Both stroke and otoneurologic workup are recommended. To our knowledge, this is the first case of RTI associated with subclavian steal reported.

Telemedicine in the management of non-acute headaches: A prospective, open-labelled non-inferiority, randomised clinical trial.

Objectives We determined headache patients' satisfaction with telemedicine and assessed how telemedicine influenced headache burden, compliance with diagnosis and treatment, and need for follow-up consultations. Methods During 2.5 years, patients from Northern Norway referred with non-acute headaches for a specialist consultation at Tromsø University Hospital were consecutively randomised to either telemedicine or traditional visits. Baseline data were recorded and compared to data from a three-month follow-up questionnaire (see Supplementary material). The following were evaluated: (1) satisfaction with the consultation; (2) headache status; subjective improvement, average pain intensity, treatment, headache days per month, and Headache Impact Test (HIT-6); and (3) treatment compliance and follow-up visits. Results Out of 402 consultations, 348 (86.6%) answered the questionnaire. Satisfaction was similar in the telemedicine and the traditional group (88.8% vs. 92.3%; p = 0.35). Subgroup analyses were not prespecified, but there were no differences in satisfaction among females, migraineurs, rural patients and urban patients. Improvement from baseline after three months was reported equally in the telemedicine and the traditional groups. There were also no differences in treatment compliance, but rural telemedicine patients had less-frequent headache visits at three months' follow-up (28.9% vs. 48.7%, p = 0.002). Conclusion Telemedicine is non-inferior to traditional consultations in patient satisfaction, specialist evaluation, and treatment of non-acute headaches. ClinicalTrials.gov ID: NCT02270177.

Photophobia and Seasonal Variation of Migraine in a Subarctic Population.

OBJECTIVE: To investigate associations between photophobia and seasonal variation of migraine. METHODS: In this cross-sectional study, migraineurs consecutively recruited were referred to a specialist center located above the Arctic Circle at 68-71 degrees North during a 2.5-year period. Data were obtained through a structured interview. RESULTS: In total, 302 migraineurs with a mean (±SD) age of 35.5 (±12.6) years were included. Patients who reported seasonal variation of migraine (n = 90; 29.8%) also reported more often interictal photophobia than the others (61/90, 67.8% vs 92/212, 43.4%, P < .0001). Patients reported sunlight or other bright light to trigger migraine attacks in 74.4% with seasonal migraine (SM) compared with 40.6% in patients with non-seasonal migraine (NSM) (P < .0001), but there were similar frequencies of attacks reported to be triggered by sleep, menstruation, and other precipitating factors. After adjusting for migraine with aura, migraine disability, chronic migraine, interictal photophobia, and insomnia, sunlight or other bright light, photophobia was still associated with SM (OR; 3.47, CI [95%]; 1.83-6.59, P < .0001). CONCLUSIONS: Migraineurs in a subarctic area reporting seasonal variation of attack frequency also report increased interictal photophobia independent of other clinical factors. Chronobiological mechanisms and/or increased activity in the visual system may be responsible for this phenomenon.

Reduced cranial parasympathetic tone during the remission phase of cluster headache.

BACKGROUND: Cluster headache (CH) attacks are accompanied by cranial autonomic symptoms indicative of parasympathetic hyperactivity and sympathetic dysfunction ipsilateral to the pain. We aimed to assess cranial autonomic function in CH patients during the remission phase of cluster headache. MATERIALS AND METHODS: During a remission phase, 38 episodic CH patients underwent the following: dynamic pupillometry, measurement of the superficial temporal artery diameter by ultrasound, and measurement of the retinal vessel diameters from digital retinal photographs. Pupillometry was also performed on 30 age- and sex-matched healthy controls. RESULTS: Thirty patients were included (27 men, three women, mean age 50.2 years ± 12.6). Seven patients reported occasional side shift of their headache, but with a clear predominating side. Significantly reduced average pupillary constriction velocity and retinal venular diameter on the CH pain side were found. There was no asymmetry of the superficial temporal artery diameters. Compared to healthy controls, cluster patients displayed bilaterally reduced pupillary average and maximum constriction velocities, reduced constriction in percentage and increased latency of the light reflex. CONCLUSIONS: The present findings indicate a bilaterally reduced cranial parasympathetic tone in CH patients in remission phase, with significant lateralization to the CH pain side. This implies a central origin, and a central pathophysiological model of CH is discussed.

Lack of association between cluster headache and PER3 clock gene polymorphism.

BACKGROUND: Cluster headache (CH) is regarded as a chronobiological disorder. The hypothalamic biological clock may thus be involved in the pathophysiology, but few studies have actually investigated this in CH patients. A variable number tandem repeat (VNTR) polymorphism of the PER3 clock gene has been associated to preferred daily rhythm (chronotype) in several studies. We aimed to study the distribution of PER3 VNTR polymorphisms and chronotypes in a CH population. METHODS: We used blood samples from a biobank of CH patients for genetic tests, and invited all tested patients to complete the Horne-Ostberg Morningness-eveningness Questionnaire (MEQ), the Pittsburgh sleep quality Index (PSQI) and the Shift Work Index. Genotypes were compared to a previously tested population of 432 healthy students. RESULTS: One hundred forty nine patients were genotyped, and we found no difference in PER3 VNTR polymorphisms between patients and controls. Seventy-four patients completed the MEQ (54 men, 20 women, mean age 52.3 years ± 13.4), and chronotypes were as follows: 12 % morning-, 37 % intermediate-, and 51 % evening types. Compared with a previous Danish study of CH patients and controls, there were no difference in chronotype distribution. Sixty percent of patients were defined as bad sleepers (PSQI >5), and 51 % of patients currently employed were shift workers. CONCLUSIONS: No association between CH, PER3 VNTR polymorphism and chronotype was found in this study.

Multiple sclerosis in the far north--incidence and prevalence in Nordland County, Norway, 1970-2010.

BACKGROUND: The risk of multiple sclerosis (MS) increases with increasing latitude. Taking into consideration that Norway has a large latitude range, a south-to-north gradient would be expected. However, previous studies have reported an uneven distribution of the disease in Norway, with a relatively low prevalence in the most northern parts of the country. We describe the incidence and prevalence of MS in a county in the north of Norway over a period of 40 years. METHODS: All patients with MS living in Nordland County in the period 1970-2010 were identified by reviewing hospital charts. The patients were included if they met the criteria of definitive or probable MS according to Poser [Ann Neurol 13:227-231, 1983] or MS according to McDonalds [Ann Neurol 50:121-127, 2001]. Point prevalence at the beginning of the decades was calculated. The average annual incidence was calculated for 5-year periods. RESULTS: The total crude prevalence on January 1, 2010 was 182.4 per 100 000. The annual incidence continuously increased from 0.7 per 100 000 in 1970 - 1974 to 10.1 per 100,000 in 2005 - 2009. The time delay from the first symptom to diagnosis was stable from 1975 to 2010. The proportion of primary progressive MS in the prevalence numbers was 38.2% in 1980, and decreases continuously, to 18.6% in 2010. The female to male prevalence ratio has been stable since 1990 at 2.2 to 1. CONCLUSION: The prevalence and the incidence of MS have steadily increased over a 40 year period. Nordland County is a high-risk area for MS.

Histamine in migraine and brain.

BACKGROUND: Histamine has been studied in both health and disease since the initial description a century ago. With its vasodilative effect, it was suggested early on to be involved in the pathophysiology of migraine. Over the past 25 years, much has been learned about histamine as a neurotransmitter in the central nervous system. The role of this neurotransmitter system in migraine has not been previously reviewed. OBJECTIVE: Discuss a potential role of the brain histaminergic system in migraine. METHODS: Unstructured literature search with a no specific hypothesis-driven approach. RESULTS: There is substantial evidence that systemically given histamine may elicit, maintain, and aggravate headache. The mechanisms for this are not known, and histamines do not penetrate the blood-brain barrier (BBB). However, circulating histamine may influence hypothalamic activity via the circumventricular organs that lack BBB. In the rat, prolonged activation of meningeal nociceptors induced by dural mast cell degranulation has been observed. Subcutaneous injections of N-alpha-methyl histamine, a catabolite of histamine with high affinity to the histamine H3 receptor, probably have some migraine preventive effect. A negative feedback on histamine release from mast cells in proximity to C-fiber endings has been a postulated mechanism. Most antihistamines have shown to be ineffective as acute medication for migraine. Two centrally acting potent H1 receptor antagonists (cinnarizine and cyproheptadine) have been reported to be efficacious in preventing migraine. However, the proof for this is limited, and their efficacy has been ascribed other actions than the antihistaminergic. In general, lack of specificity and side effects limit the potential use of centrally acting H1 and H2 antagonists. Brain histamine is synthesized by neurons that are restricted to the posterior basal hypothalamus, more specific to the tuberomamillary nucleus (TMN), and that project practically to the whole central nervous system. The posterior hypothalamus is a suspected locus in quo in several primary headaches. Recently, a positron emission tomography study performed in the prodromal phase of migraine attacks supported the idea of initial involvement of this area. In another recent study, the thalamic nuclei receiving trigeminal output was also shown to have direct connections with the ventral TMN. The central histaminergic system plays an important role in the complex sleep-wake cycle, promoting cortical excitability during wakening and attention, and it consolidates the wake state. The period of the day, in the evenings and during the night, when there is reduced susceptibility for migraine attacks corresponds with less central histaminergic firing. Activation of both the H3 and the H4 receptor promotes inhibitory actions on neurons. The H3 receptor causes autoinhibition of the histaminergic neurons themselves, and centrally acting H3 receptor agonist prodrugs have shown to both inhibit neurogenic inflammation in dura, to induce sleep, and to produce antinociception. There are no registered ongoing studies on H3 and H4 receptor ligands in migraine. CONCLUSION: The role of the central histaminergic system in migraine is largely unexplored, but findings from preclinical research may be linked to several aspects of the disorder. The histaminergic system of the brain may play an important role, especially in the initial phase of an attack, and histamine H3 and H4 receptor ligands may potentially have migraine prophylactic properties. However, the basis for this is still circumstantial, and the evidence is lacking.

Patient satisfaction with conventional, complementary, and alternative treatment for cluster headache in a Norwegian cohort.

OBJECTIVE: Cluster headache (CH) may cause excruciating pain and not all patients get satisfactory help. Patient dissatisfaction with general practitioners (GPs) and neurologists, and use of complementary and alternative treatment (CAM) may reflect this. The authors studied patient satisfaction with doctors' treatment and use of CAM in a Norwegian CH cohort. SUBJECTS: A total of 196 subjects with a cluster headache diagnosis were identified in the registers of two neurological departments in North Norway. DESIGN: Of these, 70 with a confirmed diagnosis according to the second edition of the International Classification of Headache Disorders (ICHD-2) completed a comprehensive questionnaire with questions concerning satisfaction with doctors' treatment, use of CAM, and effect of both treatment regimes. RESULTS: Satisfaction with doctors' treatment was reported in 44/70 (63%) (GPs) and 50/70 (71%) (neurologists) while 39/70 (56%) were satisfied with both. Too long a time to diagnosis, median four years, was the most commonly reported claim regarding doctors' treatment. Use of CAM was reported in 27/70 (39%), and 14/70 (20%) reported experience with ≥ 2 CAM. Ten patients reported benefit from CAM (37% of "CAM users"). The average cluster period was longer in CAM-users than others (p = 0.02), but CAM use was not associated with age, education, use of medication, effect of conventional treatment, duration of cluster attacks, or time to diagnosis. CONCLUSION: About two-thirds of CH patients were satisfied with treatment from either GPs or neurologists, and about one-third had used CAM. Despite experiencing diagnostic delay and severe pain, cluster patients seem in general to be satisfied with doctors' conventional treatment.

Repeat expansions in AR, ATXN1, ATXN2 and HTT in Norwegian patients diagnosed with amyotrophic lateral sclerosis.

Genetic repeat expansions cause neuronal degeneration in amyotrophic lateral sclerosis as well as other neurodegenerative disorders such as spinocerebellar ataxia, Huntington's disease and Kennedy's disease. Repeat expansions in the same gene can cause multiple clinical phenotypes. We aimed to characterize repeat expansions in a Norwegian amyotrophic lateral sclerosis cohort. Norwegian amyotrophic lateral sclerosis patients (n = 414) and neurologically healthy controls adjusted for age and gender (n = 713) were investigated for repeat expansions in AR, ATXN1, ATXN2 and HTT using short read exome sequencing and the ExpansionHunter software. Five amyotrophic lateral sclerosis patients (1.2%) and two controls (0.3%) carried ≥36 repeats in HTT (P = 0.032), and seven amyotrophic lateral sclerosis patients (1.7%) and three controls (0.4%) carried ≥29 repeats in ATXN2 (P = 0.038). One male diagnosed with amyotrophic lateral sclerosis carried a pathogenic repeat expansion in AR, and his diagnosis was revised to Kennedy's disease. In ATXN1, 50 amyotrophic lateral sclerosis patients (12.1%) and 96 controls (13.5%) carried ≥33 repeats (P = 0.753). None of the patients with repeat expansions in ATXN2 or HTT had signs of Huntington's disease or spinocerebellar ataxia type 2, based on a re-evaluation of medical records. The diagnosis of amyotrophic lateral sclerosis was confirmed in all patients, with the exception of one patient who had primary lateral sclerosis. Our findings indicate that repeat expansions in HTT and ATXN2 are associated with increased likelihood of developing amyotrophic lateral sclerosis. Further studies are required to investigate the potential relationship between HTT repeat expansions and amyotrophic lateral sclerosis.

Insomnia and periodicity of headache in an arctic cluster headache population.

OBJECTIVE: To assess the prevalence of chronic insomnia and the periodicity of headache attacks in an Arctic cluster headache population. BACKGROUND: Cluster headache is a sleep-related disorder, and attacks have both circadian and circannual rhythmicity. METHODS: Through a retrospective hospital chart review, we identified all subjects diagnosed with episodic cluster headache (ICD-10 G 44.0) at the Neurological Departments in Northern Norway (located north of 66°33'N) between January 1, 2000 and December 31, 2010. Patients with a confirmed diagnosis (ICHD-2) received a comprehensive questionnaire covering demographic data, clinical characteristics, sleep, and periodicity of attacks. RESULTS: A total of 196 subjects were registered, and 178 received the questionnaire. The response rate was 88/178 (49%). Fifty-eight men (aged 49.2 ± 13.6) and 12 women (aged 49.7 ± 15.5) were included. Forty percent of the responders suffered from chronic insomnia (Diagnostic and Statistical Manual of Mental Disorders 4th edition). Forty-nine percent of the responders and 42% of the non-responders were shift workers, which is much higher than compared with the general population (24%). Insomnia was significantly associated with shift work and experiencing longer-lasting cluster bouts. One third attributed their insomnia to the cluster headache. Thirty-seven percent reported a seasonal predilection of the cluster periods, and 58% a diurnal periodicity of attacks. Eighty percent often or always had headache attacks during sleep, the most frequent time interval being at 12:00-4:00 am. Shift workers were significantly more likely to see lack of sleep as a cluster attack trigger than daytime workers. CONCLUSIONS: Chronic insomnia and shift work seem to be common among Arctic cluster headache patients. The small number of subjects included in this study implies that conclusions should be drawn with caution, but the findings support the idea of cluster headache as a circadian rhythm disorder.

Migraine among Norwegian neurologists.

BACKGROUND: Previous studies have shown a high prevalence of migraine among neurologists. The main objective of this study was to assess the prevalence of migraine and its subtypes among neurologists in Norway. METHOD: Questionnaire-based cross-sectional study among every Norwegian neurologist registered on March 19, 2010. RESULTS: Among the 384 neurologists, 245 (64%) participated. Of these, 95 (39%) reported having experienced migraine aura, and 86 having experienced migraine headache (35%). By employing the International Headache Society criteria for migraine with regard to the number of attacks, the gender-adjusted lifetime and 1-year prevalence was 38.7% (95% CI 30.3-47.7) and 33.8% (95% CI 25.9-47.2), respectively. Age-adjusted 1-year prevalence of migraine headache (not including subjects experiencing visual aura only) for men was 15.9% and for women 36.7%, which gives an overall age and gender-adjusted prevalence of 26.3% (95% CI 18.5-34.2). Solitary auras were experienced by 83 (34%), of which 73 (30%) had experienced this twice or more frequently. The majority of the neurologists thought that migraine was underdiagnosed and undertreated, 70% and 68%, respectively. CONCLUSION: The study confirms the results of previous studies, indicating that migraine, including visual aura, is more common among neurologists than what would be expected from population-based studies. Because this group, through professional experience with the condition, can make accurate diagnoses in themselves, and will have fewer problems with recalling headache episodes, the prevalence figures obtained may give the most precise estimate of the true population prevalence.

[Acquired Horner's syndrome]. / Ervervet Horners syndrom.

BACKGROUND: Horner's syndrome is characterized by the classic triad of eyelid ptosis, miosis and facial anhidrosis and is caused by an interruption of the oculosympathetic nerve pathway somewhere between its origin in the hypothalamus and the eye. MATERIAL AND METHODS: This review is based on own experiences and a discretionary selection of articles found through non-systematic searches in PubMed. Cases from own practice serve as examples. RESULTS: Based on localization of the nerve pathway interruption, a Horner's syndrome is often classified as central, pre- or postganglionic. For the central type the syndrome is associated with other symptoms and signs from the central nervous system. The preganglionic type is most often caused by a tumor or trauma. The postganglionic type is often associated with pain/headache; most frequently it is seen as a consequence of carotid artery dissection or during cluster headache. Anhidrosis is rarely prominent, and in the postganglionic subtype it is virtually absent. Pharmacological tests can be used in diagnostics. Apraclonidine seems to be a good alternative to cocaine to confirm Horner's syndrome. MRI is generally recommended in the evaluation, if necessary with special sequences. INTERPRETATION: The path of the long oculosympathetic fibers is complex and not fully understood. Topographic diagnostics may be challenging, but in most cases a specific cause is identified.

Effectiveness of Natalizumab in Achieving No Evidence of Disease Activity (NEDA-3)-Data From a Local Norwegian Cohort.

Objective: We aimed to determine the effectiveness of natalizumab (NTZ) by assessing overall No Evidence of Disease Activity 3 (NEDA-3) in a local Norwegian cohort. Background: NTZ is an immunomodulating drug used in the treatment of multiple sclerosis (MS). It has typically been used as a second-line treatment, but certain patients with high disease activity have started directly with NTZ. Methods: This retrospective cohort study includes all patients who received NTZ for relapsing-remitting MS at Nordland Hospital in the period 2008-2018. In June 2019, status for every patient was assessed, and a survival curve was used to show the cumulative probability of achieving NEDA-3 over time. Results: The cohort consisted of 66 patients, 49 women and 17 men with a mean age of 40.0 ± 10.8 years. Each patient received on average 45.8 ± 36.4 NTZ infusions. Mean age and Expanded Disability Status Scale (EDSS) at first infusion was 34.8 ± 10.5 and 3.2 ± 1.9, respectively. Prior to NTZ treatment, 83% had used other disease modulating drugs and 65% were anti-JC virus (JCV) seronegative. During the study period, seven patients converted to seropositive. In 2019, 40 patients had switched or stopped treatment: 19 due to positive JCV serostatus, 9 due to disease activity, 7 due to adverse effects or complications (1 progressive multifocal leukoencephalopathy), 2 due to pregnancy, and 3 due to autologous hematopoietic cell transplantation abroad. Three patients experienced rebound in the wake of discontinuation (7.5%). Of the patients receiving NTZ for more than 3 years (n = 33), 50% had achieved NEDA-3 after 3 years. Compared to those with evidence of disease activity (EDA), these NEDA-3 patients had significant lower EDSS score before first NTZ treatment (p = 0.04). They were also slightly, but not significantly, younger at debut of their MS, at the diagnosis and at first NTZ treatment. Of all the patients who ever started on NTZ, 23% had achieved NEDA-3 5 years later. The mean EDSS in 2019 was 3.6 ± 2.5. Conclusion: Despite the high rate of treatment switch, mainly due to the risk of PML, almost one in four who started on NTZ achieved NEDA-3 after 5 years, and the overall disease progression was low in the total cohort. Treating less advanced disease seems to predict better long-term stability.

Synesthesia and migraine: case report.

BACKGROUND: Synesthesia is, as visual migraine aura, a common and fascinating perceptual phenomenon. Here we present a unique case with synesthesias exclusively during visual migraine auras. CASE PRESENTATION: A 40-year-old woman with a cyclic mood disorder had suffered from migraine with visual aura for several years. On several occasions she had experienced "mixing of senses" during the aura phase. Staring at strong bright light she could experience intense taste of lemon with flow from the salivary glands. CONCLUSION: Acquired synesthesia, exclusively coincident with migraine aura, gives support to the idea of an anomalous cortical processing underlying the phenomenon.

Sudden Caffeine Withdrawal Triggers Migraine-A Randomized Controlled Trial.

Objective: Assessing the effects of caffeine withdrawal on migraine. Background: The effects of caffeine withdrawal on migraineurs are at large unknown. Methods: This was a randomized, double-blind, crossover study (NCT03022838), designed to enroll 80 adults with episodic migraine and a daily consumption of 300-800 mg caffeine. Participants substituted their estimated dietary caffeine with either placebo capsules or capsulated caffeine tablets for 5 weeks before switching the comparators for 5 more weeks. Results: The study was terminated due to low recruitment. Ten subjects with a mean age of 46.3 ± 9.9 years, BMI of 24.9 ± 3.7, and a mean blood pressure of 134/83 ± 17/12 mmHg were enrolled. The average consumption of caffeine per day was 539 ± 196.3 mg. The average monthly headache days and migraine attack frequency at baseline was 11.5 ± 4.9 and 5.2 ± 1.2, respectively. At baseline Pittsburgh Sleep Quality Index was 5.8 ± 2.5 and HIT-6 was 62.8 ± 3.9. There were no differences in these or in parameters from actigraphy during the caffeine period compared with the placebo period. One subject withdrew just after entering the study. In the remaining nine, withdrawal triggered severe migraine attacks in seven, causing one more drop-out, and a typical caffeine withdrawal syndrome in two. Caffeine continuation did not trigger migraines, but one attack occurred in the wake of caffeine reintroduction. Conclusions: The study failed to answer how caffeine withdrawal affects migraineurs over time, but showed that abrupt withdrawal of caffeine is a potent trigger for migraine attacks.