The long and winding road: the journey taken by headache sufferers in search of help.

AimTo outline the pathways a cohort of first attendees to our headache clinics had taken over the years in search of explanations and treatment for their headaches. To establish a greater awareness of the shortcomings and failures in their medical journey in the hope that better headache management will emerge in primary care. BACKGROUND: At first attendance in primary care most headache sufferers will not receive a firm diagnosis. Treatments provided are often ineffective and so many patients embark on a somewhat random self-made journey searching for a remedy. If they reach a Headache Clinic the most common diagnoses are 'chronic migraine' and 'medication overuse headache'. They are either no better or worse than when their headaches first started despite their efforts. METHOD: We undertook a prospective questionnaire-based study of over 200 patients on first attendance at each of our headache clinics, three based in District General Hospitals and one in a tertiary referral centre. We documented the patients' headache characteristics, the 'burden' of their headaches, functional handicap and the financial costs incurred seeking help before referral. We also documented what our patients understood about their headache disorder and the treatments previously tried.FindingsMost patients had not been given a formal diagnosis in primary care and many remained unconvinced of the benign nature of their headache problem and wanted further investigations. A few had sought help from headache charities. Many had unrealistic attitudes to their problem and medication overuse was rife. A few patients had been offered triptans in primary care. Key deficiencies in the primary care management of these patients included failure to provide a formal headache diagnosis, inadequate understanding of the nature and mechanism of headaches and failure to follow a resilient management strategy. We provide a more effective management pathway in primary care.

Modified Valsalva test differentiates primary from secondary cough headache.

BACKGROUND: The current definition of cough headache includes provocation of the symptom by Valsalva manoeuvre, and it is generally believed that all cough headache results from a sudden increase in intracranial pressure. We sought to question that presumption and to determine whether the Valsalva test might distinguish primary from secondary cough headache. METHODS: We examined 16 consecutive cough headache patients using a modified Valsalva test (exhalation into the connecting tube of a standard anaeroid sphygmomanometer to 60 mm Hg for 10 seconds). A positive response was recorded if the manoeuvre provoked headache. All patients subsequently underwent brain MRI. RESULTS: None of the patients had neurological signs. Eleven had positive modified Valsalva tests. Ten were found subsequently to have posterior fossa pathologies (secondary cough headache: 8 Chiari Type 1 malformations, 2 posterior fossa meningiomas). The cough headache was relieved following surgery in all cases. One patient with a positive Valsalva test had an apparently normal brain MRI but measurements of hindbrain and posterior fossa dimensions were consistent with 'posterior fossa crowdedness'. The remaining 5 patients had negative (4 patients) or equivocal (1 patient) Valsalva tests and normal MRI scans (primary cough headache). CONCLUSIONS: These findings suggest that secondary cough headache results from a transient increase in intracranial CSF pressure during exertion in the presence of obstruction to normal cerebrospinal fluid dynamics. The modified Valsalva test can also determine whether tonsillar herniation found on brain MRI is symptomatic. Primary cough headache appears to be caused by a different mechanism, possibly through congestion of the orbital venous plexus in the presence of jugular venous incompetence and a reduced threshold for trigeminal sensory activation.

Acetylcholine receptor antibodies in patients with genetic myopathies: clinical and biological significance.

We report two patients with facioscapulohumeral muscular dystrophy (FSHD) presenting with atypical clinical features. Both were found to have antibodies to acetylcholine receptor (AChR-abs) and improved with immunosuppression. AChR-abs have also been reported in patients with other genetic myopathies and it is unlikely that the association is coincidental. There is increasing evidence that muscle fibre degeneration can cause innate immune responses (autoinflammation) that may lead to the breaking of immune tolerance and the generation of autoantibodies to muscle proteins. We compare and contrast this process with the pathogenesis of archetypical myasthenia gravis.

Multi-minicore disease and atypical periodic paralysis associated with novel mutations in the skeletal muscle ryanodine receptor (RYR1) gene.

The skeletal muscle ryanodine receptor plays a crucial role in excitation-contraction (EC) coupling and is implicated in various congenital myopathies. The periodic paralyses are a heterogeneous, dominantly inherited group of conditions mainly associated with mutations in the SCN4A and the CACNA1S genes. The interaction between RyR1 and DHPR proteins underlies depolarization-induced Ca(2+) release during EC coupling in skeletal muscle. We report a 35-year-old woman presenting with signs and symptoms of a congenital myopathy at birth and repeated episodes of generalized, atypical normokalaemic paralysis in her late teens. Genetic studies of this patient revealed three heterozygous RYR1 substitutions (p.Arg2241X, p.Asp708Asn and p.Arg2939Lys) associated with marked reduction of the RyR1 protein and abnormal DHPR distribution. We conclude that RYR1 mutations may give rise to both myopathies and atypical periodic paralysis, and RYR1 mutations may underlie other unresolved cases of periodic paralysis with unusual features.

A systematic review of antioxidant treatment for amyotrophic lateral sclerosis/motor neuron disease.

Free radical accumulation and oxidative stress have been proposed as contributing to the progression of amyotrophic lateral sclerosis (motor neuron disease). A range of antioxidant medications is available, and has been studied. We aimed to examine the effects of antioxidant medication in the treatment of people with amyotrophic lateral sclerosis, and searched the Cochrane Neuromuscular Disease Group Trials register (August 2005), MEDLINE (January 1966 to August 2005), EMBASE (January 1980 to August 2005) and other sources. Selection criteria were all randomized or quasi-randomized controlled trials of antioxidant treatment for amyotrophic lateral sclerosis. The authors independently applied the selection criteria, assessed study quality and two authors performed independent data extraction. The search identified 23 studies for consideration but only nine studies met the inclusion criteria. Only two studies used our predetermined primary outcome measure as the primary outcome measure (survival at 12 months treatment). However, sufficient data were available from four studies to allow analysis of this outcome measure, and a meta-analysis was performed. In the individual studies no significant effect was observed for vitamin E 500 mg twice daily; vitamin E 1 g five times daily; acetylcysteine 50 mg/kg daily subcutaneous infusion; or a combination of L-methionine 2 g, vitamin E 400 International Units, and selenium 0.03 mg three times daily (Alsemet). No significant effect on the primary outcome measure was observed in a meta analysis of all antioxidants combined. No significant differences were demonstrated in any of the secondary outcome measures. In the opinion of the reviewers, there is insufficient evidence of efficacy of individual antioxidants, or antioxidants in general, in the treatment of people with amyotrophic lateral sclerosis. One study reported a mild positive effect, but this was not supported by the analysis we used. Generally, the studies were poorly designed, and underpowered, with low numbers of participants and of short duration. Further well-designed trials of medications such as vitamin C and E are unlikely to be performed. If future trials of antioxidant medications are performed, careful attention should be given to sample size, outcome measures, and duration of the trial. The high tolerance and safety, and relatively low cost of vitamins C and E, and other considerations related to the lack of other effective treatments for amyotrophic lateral sclerosis, explain the continuing use of these vitamins by physicians and people with amyotrophic lateral sclerosis. While there is no substantial clinical trial evidence to support their clinical use, there is no clear contraindication.