Assessing and managing medication overuse headache in Australian clinical practice.

More than 3 million Australians are estimated to have migraine disorders, and over a quarter of a million Australians are estimated to have medication overuse headache (MOH). The personal, societal and economic burden of MOH is high. MOH impacts an individual's ability to work or study, care for family or themselves, culminating in poor quality of life. Accurate and timely diagnosis and treatment of MOH are imperative. Withdrawal failures and relapse rates are high in MOH. Treatment of MOH is aimed at ceasing medication overuse and reducing monthly migraine days with the aim of achieving a pattern of well-controlled episodic migraine. Current treatment approaches in routine practice include withdrawal with preventive treatment, withdrawal with optional preventive treatment in the subsequent weeks and preventive treatment without withdrawal. This viewpoint article provides an overview of managing MOH in Australian clinical practice, with a focus on the importance of patient education and the role of preventive treatment in supporting patients as they withdraw from acute migraine medication(s).

Intravenous Lidocaine and Ketamine Infusions for Headache Disorders: A Retrospective Cohort Study.

Introduction: The use of lidocaine (lignocaine) and ketamine infusion in the inpatient treatment of patients with headache disorders is supported by small case series. We undertook a retrospective cohort study in order to assess the efficacy, duration and safety of lidocaine and ketamine infusions. Methods: Patients admitted between 01/01/2018 and 31/07/2021 were identified by ICD code and electronic prescription. Efficacy of infusion was determined by reduction in visual analog score (VAS), and patient demographics were collected from review of the hospital electronic medical record. Results: Through the study period, 83 infusions (50 lidocaine, 33 ketamine) were initiated for a headache disorder (77 migraine, three NDPH, two SUNCT, one cluster headache). In migraine, lidocaine infusion achieved a ≥50% reduction in pain in 51.1% over a mean 6.2 days (SD 2.4). Ketamine infusion was associated with a ≥50% reduction in pain in 34.4% over a mean 5.1 days (SD 1.5). Side effects were observed in 32 and 42.4% respectively. Infusion for medication overuse headache (MOH) led to successful withdrawal of analgesia in 61.1% of lidocaine, and 41.7% of ketamine infusions. Conclusion: Lidocaine and ketamine infusions are an efficacious inpatient treatment for headache disorders, however associated with prolonged length-of-stay and possible side-effects.

Cluster headache in adults.

Cluster headache is characterised by attacks of very severe, unilateral headache lasting 15-180 minutes, up to eight times per day. The attacks are associated with cranial autonomic symptoms on the same side and a sense of agitation or restlessness First-line acute abortive treatments include intranasal or subcutaneous sumatriptan or high-flow oxygen. Neuromodulation may benefit some patients First-line preventive therapy is high-dose verapamil. Close monitoring is required for the adverse effect of arrhythmia There are several emerging therapies that have either proven efficacy, or possible benefit for cluster headache. They include drugs aimed at the calcitonin gene-related peptide.

Inflammatory complications of CGRP monoclonal antibodies: a case series.

BACKGROUND: Calcitonin gene-related peptide (CGRP) is expressed throughout the body and is a known mediator of migraine, exerting this biological effect through activation of trigeminovascular, meningeal and associated neuronal pathways located in close proximity to the central nervous system. Monoclonal antibodies (mAb) targeting the CGRP pathway are an effective new preventive treatment for migraine, with a generally favourable adverse event profile. Pre-clinical evidence supports an anti-inflammatory/immunoregulatory role for CGRP in other organ systems, and therefore inhibition of the normal action of this peptide may promote a pro-inflammatory response. CASES: We present a case series of eight patients with new or significantly worsened inflammatory pathology in close temporal association with the commencement of CGRP mAb therapy. CONCLUSION: This case series provides novel insights on the potential molecular mechanisms and side-effects of CGRP antagonism in migraine and supports clinical vigilance in patient care going forward.

Calcitonin gene related peptide in migraine: current therapeutics, future implications and potential off-target effects.

Migraine is the second largest cause of years lost to disability globally among all diseases, with a worldwide prevalence over 1 billion. Despite the global burden of migraine, few classes of therapeutics have been specifically developed to combat migraine. After 30 years of translational research, calcitonin gene-related peptide (CGRP) inhibitors have emerged as a promising new tool in the prevention of migraine. Like all new therapeutics; however, we have limited real-world experience and CGRP has several known systemic actions that warrant consideration. This article provides a narrative review of the evidence for CGRP antagonists and summarises the known and potential side effects that should be considered.

Genetic prion disease: D178N with 129MV disease modifying polymorphism-a clinical phenotype.

BACKGROUND: Human prion diseases are a group of rare neurological diseases with a minority due to genetic mutations in the prion protein (PRNP) gene. The D178N mutation is associated with both Creutzfeldt-Jakob disease and fatal familial insomnia with the phenotype modified by a polymorphism at codon 129 with the methionine/valine (MV) polymorphism associated with atypical presentations leading to diagnostic difficulty. CASE: We present a case of fatal familial insomnia secondary to a PRNP D178N mutation with 129MV disease modifying polymorphism who had no family history, normal MRI, electroencephalography (EEG), cerebrospinal fluid (CSF) and positron emission tomography findings and a negative real-time quaking-induced conversion result. CONCLUSION: Patients with genetic prion disease may have no known family history and normal EEG, MRI brain and CSF findings. PRNP gene testing should be considered for patients with subacute progressive neurological and autonomic dysfunction.

Progressive multifocal leukoencephalopathy secondary to hepatitis C virus infection-related T-cell lymphopenia.

Progressive multifocal leukoencephalopathy (PML) is an uncommon neurological condition known to occur in the setting of T-cell immune suppression. We report a case of hepatitis C virus (HCV) infection-related T-cell lymphopenia manifesting as PML. HCV treatment and transient viral suppression resulted in immunological recovery with clinical stabilisation.

Long-term study of the efficacy and safety of OnabotulinumtoxinA for the prevention of chronic migraine: COMPEL study.

BACKGROUND: OnabotulinumtoxinA is approved for the prevention of headache in those with chronic migraine (CM); however, more clinical data on the risk-benefit profile for treatment beyond one year is desirable. METHODS: The Chronic Migraine OnabotulinuMtoxinA Prolonged Efficacy open Label (COMPEL) Study ( ClinicalTrials.gov , NCT01516892) is an international, multicenter, open-label long-term prospective study. Adults with CM received 155 U of onabotulinumtoxinA (31 sites in a fixed-site, fixed-dose paradigm across 7 head/neck muscles) every 12 weeks (±7 days) for 9 treatment cycles (108 weeks). The primary outcome was headache day reductions at 108 weeks; secondary outcomes were headache day reductions at 60 weeks and change in the 6-item Headache Impact Test (HIT-6) score. Safety and tolerability were assessed by reviewing the frequency and nature of adverse events (AEs). AEs were determined at each visit through patient self-report, general non-directed and, for specific AEs, directed questioning, and physical examination. Subgroup analyses for safety and efficacy included, but were not limited to, patients with/without concomitant oral preventive treatment and acute medication overuse at baseline. RESULTS: Enrolled patients (N = 716) were 18-73 years old and most were female (n = 607, 84.8%). At baseline, patients reported an average 22.0 (SD = 4.8) headache days per month. 52.1% of patients (n = 373) completed the study. By 60 and 108 weeks, a significant reduction in headache days (- 9.2 days and - 10.7 days, respectively, P < 0.0001) was observed. Significant improvements (P < 0.0001) in HIT-6 scores (- 7.1 point change at week 108) were also demonstrated. 131 patients (18.3%) reported ≥1 treatment-emergent adverse events; most frequently reported was neck pain (n = 29, 4.1%). One patient reported a serious treatment-related adverse event (rash). No deaths were reported. CONCLUSIONS: The COMPEL Study provides additional clinical evidence for the consistency of the efficacy and for the long-term safety and tolerability of onabotulinumtoxinA for the prevention of headache in those with CM who have been treated with onabotulinumtoxinA every 12 weeks over 2 years (9 treatments) with the fixed-site, fixed-dose injection paradigm. TRIAL REGISTRATION: Trial registration number: NCT01516892 . Name of registry: clinicaltrials.gov . Date of registration: January 20 2012. Date of enrollment of first patient: December 2011.

Sleep apnoea and the neurologist.

There is increasing awareness and interest in the complex and extensive inter-relationships between sleep disorders and neurological disorders. This review focuses on the clinical interactions between obstructive sleep apnoea and stroke, headaches, epilepsy, cognition and idiopathic Parkinson's disease. We highlight to the neurologist the importance of taking a sleep history and considering the diagnosis and treatment of obstructive sleep apnoea.

How to assess tendon reflexes of the lower limb in the elderly.

BACKGROUND: Clinicians frequently experience difficulty in eliciting the reflexes of elderly patients using standard methods due to paratonia/frontal rigidity. If reflexes are incorrectly thought to be absent, important diagnostic errors may be made. Neurologists use alternative methods when technical difficulties require them, but these are not widely used by non-neurologists. METHODS: A neurologist and a medical student both used standard and non-standard techniques to assess reflexes of the lower limb in geriatric inpatients, aged over 65, to determine which method permitted the most confident assessment of the presence of knee and ankle reflexes. RESULTS: 45 patients were assessed. The consultant found that in 20 patients (44%) all three knee reflex methods examined produced similar results. When the methods produced different results, the "superior patellar supine" method was the best single method overall (best or equal best in 19 patients (42%)). For the ankle reflex all four reflex methods examined produced similar results in only 7 patients (16%). When the methods produced different results the "Achilles strike elevated" method was best or equal best in 32 patients (71%) and the "plantar strike" method in 29 patients (64%). If the student had relied on standard methods alone, reflexes would have been incorrectly called absent in 28 limbs (37%) for knee jerks and 52 limbs (84%) for ankle jerks. Supplementing standard methods with alternative methods reduced these error rates to 19% and 21% respectively. CONCLUSIONS: Our findings indicate that a reasonable practical approach is to assess the knee reflex with the standard method and then, if a definite reflex has not been recorded, move on to use the "superior patellar supine" method; and for the ankle reflex begin with the "plantar strike method" and then, if necessary, move on to use the "Achilles strike elevated" method.

Mechanisms of upper limb amyotrophy in spinal disorders.

Upper limb amyotrophy may occur as an indirect consequence of various spinal disorders, including ventral longitudinal intraspinal fluid collection, Hirayama disease and high cervical cord compression. We present patients who suffer from each of these and review the literature on the three conditions with emphasis on the pathogenesis of amyotrophy. We propose that pathology some distance from the lower cervical spinal cord may affect normal venous drainage, resulting in venous congestion and reduced perfusion pressure which, in turn, could result in anterior horn cell dysfunction in all three disorders.

Chronic migraine and chronic daily headache in the Asia-Pacific region: a systematic review.

BACKGROUND: Data on the prevalence and characteristics of chronic migraine (CM) and chronic daily headache (CDH) in the Asia-Pacific region are limited. METHODS: We performed a systematic review on this topic, searching for studies published from 1996 to 2012 that reported the prevalence (population-based studies) or frequency (clinic studies) of CM or CDH. We calculated 95% confidence intervals for the prevalence in population studies. Results were qualitatively described. RESULTS: Seven population studies and 19 hospital clinic studies from Asia were included. The CDH prevalence in population studies was 1.0-3.9% (median 2.9%). Only two studies from Taiwan reported the population prevalence of CM (1.0% and 1.7%). In addition, we derived a prevalence of 0.6% from a Malaysian study. Eleven clinic studies reported a CM frequency of 4.7-82% (median 52%) as a subset of CDH; classification of medication overuse varied. CM was associated with substantial disability. CONCLUSIONS: The prevalence of CM and CDH in Asia appears lower than the global average, but applying the above prevalence estimates to the Asia-Pacific population would suggest that CM alone affects between 23 and 65 million individuals in the region.

Commentary: development and validation of the Asian Migraine Criteria (AMC).

Precise and manageable diagnostic criteria are vital for researchers and clinicians dealing with headache. The lack of clear and accessible markers of the biological distinctions between different types of headache means that criteria are determined by expert consensus. The International Classification of Headache Disorders (ICHD) criteria are the current benchmark and are evolving. They are effective for research as they exclude questionable cases from consideration, but in clinical practice they are used inconsistently by neurologists, and rarely by general practitioners, because of complexity. In this issue of the Journal of Clinical Neuroscience, Ghandehari et al. have proposed a new set of criteria, the Asian Migraine Criteria (AMC). These criteria perform well against the gold-standard ICHD, but are almost as complex. They do not have the simplicity of the ID Migraine tool. Nevertheless, they are welcome: any tool that general practitioners may be attracted to use that increases the accuracy of headache diagnosis is to be applauded.

Migraine prophylaxis.

There is a wide array of options for migraine prophylaxis; many of the available drugs are clearly proven to be effective and yet are underused in Australia. "New" drugs which are gaining favour for migraine prophylaxis include topiramate, candesartan, gabapentin and botulinum toxin. The evidence for efficacy is excellent for topiramate and reasonably good but limited for candesartan and gabapentin. The use of botulinum toxin is controversial and has gained substantial popularity through anecdotal experience rather than convincing published evidence. Transformed or chronic migraine with medication overuse is a particularly difficult problem. New strategies to aid in medication withdrawal are reviewed. The approach to menstrual migraine and migraine with prominent aura may differ from that for typical migraine. Novel approaches are being explored for these problems.

Management of migraine in Australian general practice.

OBJECTIVES: To determine the proportion of patients who have a diagnosis of migraine in a sample of Australian general practice patients, and to review the prophylactic and acute drug treatments used by these patients. DESIGN, SETTING AND PARTICIPANTS: A cohort of general practitioners collected data from about 30 consecutive patients each as part of the BEACH (Bettering the Evaluation and Care of Health) program; this is a continuous national study of general practice activity in Australia. The migraine substudy was conducted in June-July 2005 and December 2005-January 2006. MAIN OUTCOME MEASURES: Proportion of patients with a current diagnosis of migraine; frequency of migraine attacks; current and previous drug treatments; and appropriateness of treatment assessed using published guidelines. RESULTS: 191 GPs reported that 649 of 5663 patients (11.5%) had been diagnosed with migraine. Prevalence was 14.9% in females and 6.1% in males. Migraine frequency in these patients was one or fewer attacks per month in 77.1% (476/617), two per month in 10.5% (65/617), and three or more per month in 12.3% (76/617) (missing data excluded). Only 8.3% (54/648) of migraine patients were currently taking prophylactic medication. Patients reporting three or more migraines or two migraines per month were significantly more likely to be taking prophylactic medication (19.7% and 25.0%, respectively) than those with less frequent migraine attacks (3.8%) (P < 0.0001). Prophylactic medication had been used previously by 15.0% (96/640). The most common prophylactic agents used currently or previously were pizotifen and propranolol; other appropriate agents were rarely used, and inappropriate use of acute medications accounted for 9% of "prophylactic treatments". Four in five migraine patients were currently using acute medication as required for migraine, and 60.6% of these medications conformed with recommendations of the National Prescribing Service. However, non-recommended drugs were also used, including opioids (38% of acute medications). CONCLUSIONS: Migraine is recognised frequently in Australian general practice. Use of acute medication often follows published guidelines. Prophylactic medication appears to be underutilised, especially in patients with frequent migraine. GPs appear to select from a limited range of therapeutic options for migraine prophylaxis, despite the availability of several other well documented efficacious agents, and some use inappropriate drugs for migraine prevention.