Medication overuse headache: a critical review of end points in recent follow-up studies

No guidelines for performing and presenting the results of studies on patients with medication overuse headache (MOH) exist. The aim of this study was to review long-term outcome measures in follow-up studies published in 2006 or later. We included MOH studies with >6 months duration presenting a minimum of one predefined end point. In total, nine studies were identified. The 1,589 MOH patients (22% men) had an overall mean frequency of 25.3 headache days/month at baseline. Headache days/month at the end of follow-up was reported in six studies (mean 13.8 days/month). The decrease was more pronounced for studies including patients with migraine only (−14.6 days/month) compared to studies with the original diagnoses of migraine and tension-type headache (−9.2 days/month). Six studies reported relapse rate (mean of 26%) and/or responder rate (mean of 28%). Medication days/month and change in headache index at the end of follow-up were reported in only one and two of nine studies, respectively. The present review demonstrated a lack of uniform end points used in recently published follow-up studies. Guidelines for presenting follow-up data on MOH are needed and we propose end points such as headache days/month, medication days/month, relapse rate and responder rate defined as ≥50% reduction of headache frequency and/or headache index from baseline.     

Clinical outcome of a headache-specific multidisciplinary treatment program and adherence to treatment recommendations in a tertiary headache center: an observational study

This study investigated the outcome of a 5-day headache-specific multidisciplinary treatment program (MTP) and the adherence to treatment recommendations in 295 prospectively recruited consecutive headache patients [210 migraine, 17 tension-type headache (TTH), 68 combination headache, including 56 medication-overuse headache (MOH)]. Headache frequency decreased from 13.4 (±8.8) to 8.8 (±8.0) days per month after 12–18 months. Forty-three percent of the participants fulfilled the primary outcome (reduction of headache frequency of ≥50%), which was less likely in patients with combination of migraine and TTH compared to migraine (OR = 3.136, p = 0.002) or TTH (OR = 1.029, n.s.). Increasing number of headache days per month (OR = 1.092, p ≤ 0.0001) and adherence to lifestyle modifications (OR = 1.269, p = 0.004) predicted primary outcome. 51 of 56 MOH patients were treated successfully. Thirty-five percent of the patients were adherent to pharmacological prophylaxis, 61% to relaxation therapy, and 72% to aerobic endurance sports. MTP is effective in headache treatment. Adherence to therapy was associated with better outcome.     

Dependence scores predict prognosis of medication overuse headache: a prospective cohort from the Akershus study of chronic headache

Medication overuse headache (MOH) is a chronic headache that is common in the general population. It has characteristics similar to drug dependence, and detoxification is established as the main treatment. The majority of MOH cases are in contact with general practitioners. Our objective was to investigate whether the Severity of Dependence Scale (SDS) score could be used as predictor for the prognosis of MOH in the general population. In a cross-sectional epidemiological survey, an age- and gender-stratified sample of 30,000 persons 30 to 44 years of age was recruited via a posted questionnaire. Those individuals with self-reported chronic headache (≥15 days per month) were interviewed by neurological residents at Akershus University Hospital, Oslo. The International Classification of Headache Disorders was used. Those with MOH were re-interviewed by telephone 2 to 3 years after the initial interview. SDS scores and medication information were collected at baseline and follow-up. The main outcomes were SDS scores, termination of MOH and chronic headache from baseline to follow-up. We found the predominant overused analgesics in this sample to be simple analgesics. At follow-up, 65% of participants no longer had medication overuse, and 37% had changed to episodic headache (<15 days per month). The SDS score at baseline successfully predicted improvement for primary MOH, but not secondary MOH. The SDS scores decreased slightly from baseline to follow-up in those who stopped medication overuse, but were still significantly higher than in subjects with chronic headache without medication overuse at baseline. We conclude that the SDS score can predict successful prognosis related to detoxification of primary MOH but not in secondary MOH.     

Topo–kinesthetic memory in chronic headaches. A new test for chronic patients: preliminary report

The objective of this study was to establish if chronic headaches with medication overuse can modify a topo–kinesthetic memory test. Nineteen patients with medication overuse headache (MOH), 13 patients with chronic tension–type headache (CTTH) without medication use and a group of "normal" subjects underwent a topo–kinesthetic memory test at T0 and after one month (T1); a control group of healthy volunteers was also tested to establish the baseline in our experimental setting. After one month, in the MOH patients there was a reduction of medication overuse from 3.3±2.65 to 1.1±2.23 (p<0.01), but no significant reduction in headache frequency and severity index, quality of life, anxiety and depression scores. The navigation time at T0 was 14.3±4.97, 27.9±10.12, 34.3±15.38 and 7.5±2.33, 10.1±2.95, 11.4±3.21 for control, MOH and CTTH with closed and open eyes, respectively (p<0.02). At T1, the MOH patients reached performances with open eyes similar to the healthy controls, while with closed eyes the navigation test reached times similar to those of CTTH patients. The topokinesthetic memory test seems both able to discriminate MOH and CTTH from healthy volunteers and to be related to pain scores but is not influenced by the use of drugs.     

16th European Headache Congress 2022 meeting abstracts

Background

Initial evidence have shown the short-term efficacy of sTMS in the acute and preventive treatment of migraine. It is unknown whether this treatment approach in the long-term is effective and well tolerated in difficult-to-treat migraine.

Methods

This is a prospective, single centre, open-label, real-world analysis conducted in difficult-to-treat patients with high-frequency episodic migraine (HFEM) and chronic migraine (CM) with and without medication overuse headache (MOH), who were exposed to sTMS therapy. Patients responding to a three-month sTMS treatment, continued the treatment and were assessed again at month 12. The cut-off outcome for treatment continuation was reduction in the monthly moderate to severe headache days (MHD) of at least 30% (headache frequency responders) and/or a?≥?4-point reduction in headache disability using the Headache Impact test-6 (HIT-6) (headache disability responders).

Results

One hundred fifty-three patients were included in the analysis (F:M?=?126:27, median age 43, IQR 32.3–56.8). At month 3, 93 out of 153 patients (60%) were responders to treatment. Compared to baseline, the median reduction in monthly headache days (MHD) for all patients at month 3 was 5.0?days, from 18.0 (IQR: 12.0–26.0) to 13.0?days (IQR: 5.75–24.0) (P =?0.002, r =???0.29) and the median reduction in monthly migraine days (MMD) was 4.0?days, from 13.0 (IQR: 8.75–22.0) to 9.0 (IQR: 4.0–15.25) (P =?0.002, r =???0.29). Sixty-nine out of 153 patients (45%) reported a sustained response to sTMS treatment at month 12. The percentage of patients with MOH was reduced from 52% (N =?79/153) at baseline to 19% (N =?29/153) at month 3, to 8% (N =?7/87) at month 12. There was an overall median 4-point reduction in HIT-6 score, from 66 (IQR: 64–69) at baseline to 62 at month 3 (IQR: 56–65) (P <?0.001, r =???0.51). A total of 35 mild/moderate adverse events were reported by 23 patients (15%). One patient stopped sTMS treatment due to scalp sensitivity.

Conclusions

This open label analysis suggests that sTMS may be an effective, well-tolerated treatment option for the long-term prevention of difficult-to-treat CM and HFEM.

     

Further evidence of the positive effects of an educational and physical program on headache, neck and shoulder pain in a working community

In a controlled trial to evaluate the effectiveness of a simple educational and physical program administered to a large cohort of public servants, we previously found that 6 months following treatment the monthly frequency of headache and neck and shoulder pain and drug intake was reduced by 40% in the experimental compared with controls. These results were stable at a 12-month follow up. The program consists of brief shoulder and neck exercises to be performed several times a day, a relaxation exercise, and instructions on how to reduce parafunction and hyperfunction of the craniofacial and neck muscles during the day. The purpose of this work was to investigate whether the data previously obtained could be confirmed also in the group of 192 subjects that served as controls in first phase of the study and received the intervention in the second phase of the study. The primary endpoint was the change in frequency of headache and neck and shoulder pain expressed as the number of days per month with pain, and as the proportion of subjects with a ≥50% reduction of frequency (responder rate) at the last 2 months of the 6-month intervention period compared to the 2 months preceding the intervention (baseline). The number of days of analgesic drug consumption was also recorded. Days per month with headache at the baseline and at the end of intervention period were 6.40 and 4.58 (mean change −1.81, p < 0.0001), respectively; days with neck and shoulder pain were 7.48 and 6.18 (mean change −1.30, p = 0.0179); days of analgesic consumption were 1.67 and 1.17 (mean change −0.50, p = 0.0222). The responder rate was 42.3% for headache, 42% for neck and shoulder pain and 58.3% for drug consumption. In conclusion, this study adds further evidence on the efficacy of our program and its high acceptability in a large, unselected, working population.     

Long-term effects of a sensitisation campaign on migraine: the Casilino study

In 2003, we conducted a sensitisation campaign on migraine in the Casilino district of Rome, by sending a letter with the ID Migraine test to all the households and placing posters in the GPs’ waiting room. Out of 195 headache patients recruited, 92% had migraine while 73% had never consulted a physician for headache. The aim of this study was to evaluate the long-term impact of this campaign. The follow-up was performed by a telephone interview. The questionnaire considered the characteristics of headache, quality of life, preventive and acute treatments, drug efficacy, comorbidity and subjective usefulness of the campaign. Of the 179 migraineurs, 90.5% (mean age 40.7 ± 16.5, 139 females) were included in the follow-up. An improvement was observed in mean pain intensity (−13.9%; p < 0.0001) and mean HIT-6 score (−6.1%; p = 0.0003). The campaign was considered to be useful by 63.6% of cases, while 66.1% reported an improvement in their clinical status. Improved patients showed a decreased mean number of days with headache per month (−51.7%; p < 0.0001), pain intensity (−21.8%; p < 0.0001), headache duration (−18.1%; p = 0.0008) and HIT-6 score (−11.7%; p < 0.0001). Our data suggest that the effects of a “single shot” campaign are beneficial not only in a short-term perspective, but even in the long term. Moreover, the lack of benefit in more severe cases suggests that such patients should not be treated by GPs alone: patients in whom the HIT-6 score, frequency, severity or duration of headache worsen should be promptly referred to the headache clinic.     

Prevention of medication overuse in patients with migraine

This multi-center study compared the therapeutic effect of a cognitive-behavioral minimal contact program (MCT) to the effect of a brochure (bibliotherapy) for the prevention of medication overuse headache (MOH) in migraine patients. Seven German headache centers recruited 182 migraine patients with high triptan or analgesic intake frequency. Patients were randomly allocated to either the MCT-group, receiving both an MCT program and an educational brochure or to the biblio-group receiving only the brochure. All participants continued usual medical treatment. Course of headaches, intake of analgesics or triptans after training, 3 months post-training as well as 1-2 years (mean 15.7 months) later and psychological variables were defined as outcome variables. A significant decline was observed in the number of headache days (11.0-8.8), migraine days (7.3-5.7) and medication intake days (7.4-6.1) from pre to post in the MCT-group (p < 0.001 each) and in the biblio-group (p < 0.001 each). The pre-to-post-improvements were maintained from pre- to short- and from pre- to long-term follow-up (p < 0.001 each) in both groups. Both groups improved significantly from pre to post in psychological variables, e.g. pain acceptance: p < 0.001; pain catastrophizing: p < 0.001; functional pain coping: p < 0.001; and pain related internal control beliefs: p < 0.01. Psychological improvements remained stable in both groups at short- and long-term follow-up. During the study, none of the patients developed an MOH. MCT- and bibliotherapy are useful in migraine patients to prevent medication overuse headache or the transition of episodic to chronic headache.     

Idiopathic intracranial hypertension presenting with migraine phenotype is associated with unfavorable headache outcomes

Objective

To assess the prognostic impact of migraine headache in idiopathic intracranial hypertension (IIH).

Background

Migraine headache is common in IIH, but it is unclear whether it has prognostic relevance.

Methods

We investigated patients with IIH from the Vienna-IIH-database and differentiated migraine (IIH-MIG) from non-migraine headache (IIH-nonMIG) and without headache (IIH-noHA). Using multivariable models, we analyzed the impact of IIH-MIG on headache and visual outcomes 12 months after diagnosis.

Results

Among 97 patients (89% female, mean [SD] age 32.9 [11.1] years, median body mass index 32.0 kg/m², median cerebrospinal fluid opening pressure 310 mm), 46% were assigned to IIH-MIG, 37% to IIH-nonMIG (11% tension-type, 26% unclassifiable), and 17% to IIH-noHA. Overall, headache improvement was achieved in 77% and freedom of headache in 28%. The IIH-MIG group showed significantly lower rates for headache improvement (67% vs. 89% in IIH-nonMIG, p = 0.019) and freedom of headache (11% vs. 33% in IIH-nonMIG and 63% in IIH-noHA, p = 0.015). These differences persisted when only analyzing patients with resolved papilledema at follow-up. In contrast, visual worsening was significantly less common in IIH-MIG (9% vs. 28% in IIH-nonMIG and 31% in IIH-noHA, p = 0.045). In multivariable models, IIH-MIG was associated with a significantly lower likelihood of achieving headache improvement (odds ratio [OR] 0.57, 95% confidence interval [CI] 0.40–0.78, p < 0.001) and freedom of headache (OR 0.29, 95% CI 0.12–0.46, p < 0.001), but also a lower risk for visual worsening (OR 0.26, 95% CI 0.04–0.82, p < 0.001).

Conclusions

In IIH, migraine headache is associated with unfavorable outcomes for headache, even when papilledema has resolved, and possibly favorable visual outcome.     

Prevalence of primary headaches in Germany: results of the German Headache Consortium Study

We investigated the prevalence of migraine (MIG), tension-type headache (TTH), and chronic headache in a population-based sample in Germany. A total of 18,000 subjects aged between 18 and 65 years were screened from 2003 until 2005 using a validated questionnaire. Overall 9,944 participants (55.2%) responded (mean age 43 ± 13.1 years, 52.7% women). Headache frequency <15 days/month was reported by 5,350 (55.5%) subjects of whom 1,601 (16.6%, [95% confidence interval (95% CI): 15.9–17.4]) reported episodic MIG, 1,202 (12.5%, 95% CI 11.8–13.1) episodic TTH, and 1,150 (11.9%, [11.3–12.6]) episodic MIG + episodic TTH, 1,396 (14.5%, [13.8–15.2]) unclassifiable headache. In women, episodic MIG peaked between 36 and 40 years, episodic MIG + TTH between 18 and 35 years and episodic TTH between 56 and 66 years. In men, episodic MIG was predominant between 36 and 45 years, episodic MIG + TTH between 26 and 35 years and episodic TTH showed comparable frequency between 36 and 66 years. Headache ≥15 days/month was reported by 2.6% (n = 255, [95% CI 2.3–3]). Chronic MIG was reported by 1.1% (n = 108, [0.91–1.33]), chronic TTH (n = 50, [95% CI 0.4–0.7]), chronic MIG + TTH 0.8% (n = 74, 95% CI 0.6–0.9) and unclassifiable headache 0.2% (n = 23, [95% CI 0.1–0.3]). Chronic headache was more frequent in women compared to men with the highest prevalence between 46 and 65 years. It is of note that the number of subjects with chronic headache is small in all age groups. The results of our large, population-based study provide reliable, age- and sex-specific estimates of the prevalence of primary headache disorders in Germany. The prevalence with respect to episodic and chronic primary headache disorders in Germany is comparable to other European countries and the USA.     

Investigating the effects of weather on headache occurrence using a smartphone application and artificial intelligence: A retrospective observational cross-sectional study

Objective

To investigate the relationship between weather and headache occurrence using big data from an electronic headache diary smartphone application with recent statistical and deep learning (DL)-based methods.

Background

The relationship between weather and headache occurrence remains unknown.

Methods

From a database of 1 million users, data from 4375 users with 336,951 hourly headache events and weather data from December 2020 to November 2021 were analyzed. We developed statistical and DL-based models to predict the number of hourly headache occurrences mainly from weather factors. Temporal validation was performed using data from December 2019 to November 2020. Apart from the user dataset used in this model development, the physician-diagnosed headache prevalence was gathered.

Results

Of the 40,617 respondents, 15,127/40,617 (37.2%) users experienced physician-diagnosed migraine, and 2458/40,617 (6.1%) users had physician-diagnosed non-migraine headaches. The mean (standard deviation) age of the 4375 filtered users was 34 (11.2) years, and 89.2% were female (3902/4375). Lower barometric pressure (p < 0.001, gain = 3.9), higher humidity (p < 0.001, gain = 7.1), more rainfall (p < 0.001, gain = 3.1), a significant decrease in barometric pressure 6 h before (p < 0.001, gain = 11.7), higher barometric pressure at 6:00 a.m. on the day (p < 0.001, gain = 4.6), lower barometric pressure on the next day (p < 0.001, gain = 6.7), and raw time-series barometric type I (remaining low around headache attack, p < 0.001, gain = 10.1) and type II (decreasing around headache attack, p < 0.001, gain = 10.1) changes over 6 days, were significantly associated with headache occurrences in both the statistical and DL-based models. For temporal validation, the root mean squared error (RMSE) was 13.4, and the determination coefficient (R²) was 52.9% for the statistical model. The RMSE was 10.2, and the R² was 53.7% for the DL-based model.

Conclusions

Using big data, we found that low barometric pressure, barometric pressure changes, higher humidity, and rainfall were associated with an increased number of headache occurrences.     

Remote electrical neuromodulation for migraine prevention: A double-blind,randomized, placebo-controlled clinical trial

Objective

To assess the clinical efficacy of remote electrical neuromodulation (REN), used every other day, for the prevention of migraine.

Background

Preventive treatment is key to managing migraine, but it is often underutilized. REN, a non-pharmacological acute treatment for migraine, was evaluated as a method of migraine prevention in patients with episodic and chronic migraine.

Methods

We conducted a prospective, randomized, double-blind, placebo-controlled, multi-center trial, with 1:1 ratio. The study consisted of a 4-week baseline observation phase, and an 8-week double-blind intervention phase in which participants used either REN or a placebo stimulation every other day. Throughout the study, participants reported their symptoms daily, via an electronic diary.

Results

Two hundred forty-eight participants were randomized (128 active, 120 placebo), of which 179 qualified for the modified intention-to-treat (mITT) analysis (95 active; 84 placebo). REN was superior to placebo in the primary endpoint, change in mean number of migraine days per month from baseline, with mean reduction of 4.0 ± SD of 4.0 days (1.3 ± 4.0 in placebo, therapeutic gain = 2.7 [confidence interval −3.9 to −1.5], p < 0.001). The significance was maintained when analyzing the episodic (−3.2 ± 3.4 vs. −1.0 ± 3.6, p = 0.003) and chronic (−4.7 ± 4.4 vs. −1.6 ± 4.4, p = 0.001) migraine subgroups separately. REN was also superior to placebo in reduction of moderate/severe headache days (3.8 ± 3.9 vs. 2.2 ± 3.6, p = 0.005), reduction of headache days of all severities (4.5 ± 4.1 vs. 1.8 ± 4.6, p < 0.001), percentage of patients achieving 50% reduction in moderate/severe headache days (51.6% [49/95] vs. 35.7% [30/84], p = 0.033), and reduction in days of acute medication intake (3.5 ± 4.1 vs. 1.4 ± 4.3, p = 0.001). Similar results were obtained in the ITT analysis. No serious device-related adverse events were reported in any group.

Conclusion

Applied every other day, REN is effective and safe for the prevention of migraine.     

Headache and cognitive profile in children: a cross-sectional controlled study

We investigated whether children affected by tension-type headache and migraine without aura, compared with a healthy control group that was matched by age, culturally and socioeconomically display a diverse intellectual functioning and have a separate “cognitive profile”. A cross-sectional study was conducted from January 2006 to November 2008 at “Sapienza University” in Rome. A total of 134 children were diagnosed as being affected by either migraine without aura (93) or tension-type headache (41). On the basis of our exclusion/inclusion criteria, we enrolled 82 of these 134 children, 63 of whom were affected by migraine without aura and 19 by tension-type headache. On entry, cognitive functions were assessed in both the affected subjects and the control group by the Wechsler Intelligence Scale for Children-revised. Significant differences were found between the headache and control groups in the mean total intelligence quotient and verbal intelligence quotient scores (p < 0.001). Significant negative correlations were found between the total intelligence quotient, verbal intelligence quotient, performance intelligence quotient and the frequency of attacks (r = −0.55 and p < 0.001, r = −0.61 and p < 0.001, r = −0.29 and p < 0.01, respectively), as well as between the total intelligence quotient score and the age at headache onset (r = 0.234, p < 0.05). Our results suggest that the cognitive profile of children affected by headache should be assessed at the first child neurology outpatient observation. From a therapeutic point of view, although within a normal range, the abilities most likely to be less brilliant in such children are verbal skills.     

Effects of low workload respiratory training with steam inhalation on lung function in stable asthma: A controlled clinical study

To investigate effects of low workload respiratory muscle training (RMT) on respiratory muscle power and lung function in asthmatics, we recruited asthmatic persons who performed a 4-week training programme. The training included 20 daily ex- and inhalations with counter pressure 30% from the individual maximal expiratory pressure (MEP). Lung function was measured before and after the training programme and a follow-up period. The study also included several subjective endpoints for respiratory symptoms. A significant increase in a training group (n = 27) compared with a control group (n = 20) was seen in MEP (+12.4%, vs. +3.5%, p = 0.086), maximal inspiratory pressure (MIP) (+21.1% vs. +0.82%, p = 0.023), slow vital capacity (VC) (+3.7% vs. +1.5%, p = 0.023) and in forced expiratory time (FET, +15.5%, vs. −5.0%, p = 0.022). After being a control for group A, also group B performed similar RMT as group A. In the combined group (A and B, n = 47) MEP (11.3%, p = 0.003), MIP (19.73%, p < 0.001), VC (4.1%, p < 0.001) and FET (14.7%, p < 0.001) increased significantly from the baseline. Changes in other lung function variables were not indicative. On a scale of 1–5, the subjects perceived improvement in reduction of mucus secretion in the airways (median 3, p < 0.001), alleviation of coughing (median 3, p < 0.001) and reduction in dyspnoea (median 3, p < 0.001). As a conclusion, low workload respiratory training of 4 weeks improved respiratory muscle power and increased VC in patients with stable asthma.     

Mirtazapine improves sleep and lowers anxiety and depression in cancer patients: superiority over imipramine

Goals of the work  This study aimed to compare the effectiveness of mirtazapine and imipramine on not only the distressing symptoms of cancer patients such as pain, nausea, vomiting, appetite loss, and sleep disturbances but also depressive and anxiety symptoms. Materials and methods  Fifty-three patients with cancer who were diagnosed with major depressive disorder, anxiety disorder, or adjustment disorder were included. Twenty patients on mirtazapine, 13 patients on imipramine, and 20 patients in the control group without medication were interviewed during three visits (baseline, third week, and sixth week). Pain, nausea, vomiting, appetite loss, and sleep disturbances were evaluated with self-assessment single-symptom scales during each visit. The patients were also asked to complete the Hospital Anxiety Depression Scale (HADS) during each visit. Main results  There were no significant differences among the three visits in the mirtazapine, imipramine, or control groups in terms of pain, nausea, vomiting, or appetite loss. For the initial, middle, and late insomnia, only the mirtazapine group showed improvements (p = 0.001, p = 0.001, p = 0.003). There were also significant differences in the mean total (p = 0.03), anxiety (p = 0.003), and depression (p = 0.025) scores of HADS among the three visits for patients taking mirtazapine. There were no significant differences for HADS scores from the baseline to the end point for patients taking imipramine or control group patients. Conclusion  Our findings suggest that mirtazapine is effective for resolving insomnia as well as anxiety and depressive symptoms in cancer patients. However, more systematic research, such as placebo-controlled studies, is needed.     

Classification and clinical features of headache patients: an outpatient clinic study from China

This study aimed to analyze and classify the clinical features of headache in neurological outpatients. A cross-sectional study was conducted consecutively from March to May 2010 for headache among general neurological outpatients attending the First Affiliated Hospital of Chongqing Medical University. Personal interviews were carried out and a questionnaire was used to collect medical records. Diagnosis of headache was according to the International classification of headache disorders, 2nd edition (ICHD-II). Headache patients accounted for 19.5% of the general neurology clinic outpatients. A total of 843 (50.1%) patients were defined as having primary headache, 454 (27%) secondary headache, and 386 (23%) headache not otherwise specified (headache NOS). For primary headache, 401 (23.8%) had migraine, 399 (23.7%) tension-type headache (TTH), 8 (0.5%) cluster headache and 35 (2.1%) other headache types. Overall, migraine patients suffered (1) more severe headache intensity, (2) longer than 6 years of headache history and (3) more common analgesic medications use than TTH ones (p < 0.001).TTH patients had more frequent episodes of headaches than migraine patients, and typically headache frequency exceeded 15 days/month (p < 0.001); 22.8% of primary headache patients were defined as chronic daily headache. Almost 20% of outpatient visits to the general neurology department were of headache patients, predominantly primary headache of migraine and TTH. In outpatient headaches, more attention should be given to headache intensity and duration of headache history for migraine patients, while more attention to headache frequency should be given for the TTH ones.     

Restricted neck mobility in children with chronic tension type headache: a blinded, controlled study

The main purpose of this study was to analyze the differences in neck mobility between children with chronic tension type headache (CTTH) and healthy children, and to determine the influence of cervical mobility on headache intensity, frequency and duration. Fifty children, 13 boys and 37 girls (mean age 8.5 ± 1.6 years) with CTTH associated to peri-cranial tenderness (IHS 2.3.1) and 50 age- and sex matched children without headache (13 boys, 37 girls, mean age 8.5 ± 1.8 years, P = 0.955) participated. Cervical range of motion (CROM) was objectively assessed with a cervical goniometer by an assessor blinded to the children’s condition. Children completed a headache diary for 4 weeks to confirm the diagnosis. Children with CTTH showed decreased CROM as compared to children without headache for flexion (z = −6.170; P < 0.001), extension (z = −4.230; P < 0.001), right (z = −4.505; P < 0.001) and left (z = −4.768; P < 0.001) lateral-flexions, but not for rotation (right z = −0.802; P = 0.425; left z = −1.254; P = 0.213) and also for total range of motion for flexion-extension (z = −4.267; P < 0.001) and lateral-flexion (z = −4.801; P < 0.001), but not for rotation (z = −1.058; P = 0.293). Within CTTH children, CROM was not correlated with headache intensity, frequency or duration. Additionally, age (P > 0.125) or gender (P > 0.250) did not influence CROM in either children with CTTH or without headache. Current results support the hypothesis that the cervical spine should be explored in children with headache. Further research is also needed to clearly define the potential role of the cervical spine in the genesis or maintenance of CTTH.     

Risk factors associated with the development of thrombocytopenia in patients who received linezolid therapy

The major adverse event associated with linezolid treatment is thrombocytopenia. This study investigated risk factors associated with the development of thrombocytopenia in patients who received linezolid therapy. This was a retrospective study of patients treated with linezolid 600 mg q12h, by the oral or parenteral route, between July 2007 and June 2009. Thrombocytopenia was defined as a ≥10 × 10⁴ cells/mm³ decrease from the baseline or a ≥30% reduction. Thirty-three variables were analyzed as risk factors associated with thrombocytopenia. Multivariate analysis was performed with SPSS version 16 software. This study included 331 patients (221 male, 58.0 ± 20.2 years). The mean duration of linezolid therapy was 10.5 ± 8.7 days. Thrombocytopenia occurred in 128 patients (38.7%), of whom 21 required platelet transfusion. Thrombocytopenia developed 7.4 ± 4.8 days after linezolid initiation, and the platelet count recovered 12.3 ± 7.8 days after withdrawal. In the final steps of stepwise logistic regression analysis, 5 variables were selected: duration of linezolid therapy ≥14 days [odds ratio (OR) 3.04, 95% confidence interval (CI) 1.73–5.34, P < 0.001], creatinine clearance <50 mL/min (OR 2.32, 95% CI 1.45–3.74, P < 0.001), chronic liver disorders (OR 1.63, 95% CI 0.92–2.86, P = 0.092), and respiratory tract infections (OR 1.75, 95% CI 1.05–2.91, P = 0.031). In contrast to findings with parenteral administration, oral administration of linezolid decreased the risk of thrombocytopenia (OR 0.38, 95% CI 0.15–0.97, P = 0.042). The time to the onset of thrombocytopenia in patients with creatinine clearance <50 mL/min was significantly shorter than that in patients with creatinine clearance ≥50 mL/min (6.7 ± 4.4 and 8.5 ± 5.2 days, P = 0.039), and in patients administered orally the time to the onset of thrombocytopenia was 10.4 ± 6.6 days. Several factors influenced the occurrence of linezolid-induced thrombocytopenia. Dose adjustment may be required in at-risk patients, especially those with renal dysfunction.