The aim was to capture interdisciplinary expertise from a large group of clinicians, reflecting practice from across the UK and further, to inform subsequent development of a national consensus guidance for optimal management of idiopathic intracranial hypertension (IIH).MethodsBetween September 2015 and October 2017, a specialist interest group including neurology, neurosurgery, neuroradiology, ophthalmology, nursing, primary care doctors and patient representatives met. An initial UK survey of attitudes and practice in IIH was sent to a wide group of physicians and surgeons who investigate and manage IIH regularly. A comprehensive systematic literature review was performed to assemble the foundations of the statements. An international panel along with four national professional bodies, namely the Association of British Neurologists, British Association for the Study of Headache, the Society of British Neurological Surgeons and the Royal College of Ophthalmologists critically reviewed the statements.ResultsOver 20 questions were constructed: one based on the diagnostic principles for optimal investigation of papilloedema and 21 for the management of IIH. Three main principles were identified: (1) to treat the underlying disease; (2) to protect the vision; and (3) to minimise the headache morbidity. Statements presented provide insight to uncertainties in IIH where research opportunities exist.ConclusionsIn collaboration with many different specialists, professions and patient representatives, we have developed guidance statements for the investigation and management of adult IIH.

The lack of observable change in MTR before the first detectable gadolinium enhancement within MS lesions suggests that blood-brain barrier disruption is closely related to, but not preceded by, demyelination.

Objective-To determine non-invasively the relation between the degree of axonal loss and the extent of demyelination in chronic lesions visible on MRI in patients with diVerent subgroups of clinically definite multiple sclerosis using 1 H magnetic resonance spectroscopy ( 1 H MRS) and magnetisation transfer imaging (MT). Conventional MRI is unable to diVerentiate between the various pathological processes occurring in the multiple sclerosis lesion. There are, however, newer MR techniques which show promise in this respect. Methods-1 H MRS and MT were performed in 18 patients with clinically definite multiple sclerosis who had a wide range of disability and disease duration. Results-A significant correlation was found between a reduction in the concentration of N-acetyl aspartate (NAA; an in vivo marker of axonal loss or dysfunction) and a reduction in MT ratio (a probable marker of demyelination) in patients who had entered the secondary progressive stage of the disease. Patients with minimal disability after a disease duration of greater than 10 years-so called benign multiple sclerosis-showed a relative preservation of NAA and MT. Conclusions-Because a reduction in MT seems to be a relative marker for demyelination and a reduction of NAA from chronic lesions is indicative of axonal loss, this study supports the hypothesis that demyelination and axonal loss occur in the same chronic multiple sclerosis lesions. In addition, the degree of axonal loss and demyelination correlates with clinical heterogeneity. (J Neurol Neurosurg Psychiatry 1999;67:710-715)

There is evidence of diffuse abnormalities in NABT in addition to global brain atrophy in relapse onset MS patients, including those with recently diagnosed RRMS and benign MS. The abnormalities are greatest in patients with the more disabling SPMS. Atrophy, NABT and lesion abnormalities are all partly correlated; the processes marked by these MR measures all contribute to disability in MS, providing complementary information relevant to the complex pathological processes that occur in MS.

Axial fast FLAIR images of the brains of 40 normal volunteers in four age groups between 16 and 55 years were examined and the number and size of areas of increased white-matter signal recorded. Increased signal in the corticospinal tract region was seen at the level of the internal capsule in all subjects, extending up towards the centrum semiovale and down towards the pons for 0.5-5.5 cm (median 2.5 cm). In all cases the IIIrd and IVth ventricles were outlined by a thin line of high signal. Focal areas of high signal (caps) were seen around the frontal and occipital horns in 90% and 77% respectively; 54% of caps were asymmetrical. None of the above features varied with the age or sex of the subject, but the numbers of discrete white matter 'lesions' increased with age. The findings are used to suggest guidelines for the identification of areas of 'normal' high signal to be excluded in quantification of lesions on fast FLAIR images.

By detecting focal blood-brain barrier (BBB) breakdown, gadolinium (Gd-DTPA) contrast-enhanced T1-weighted magnetic resonance imaging (MRI) allows assessment of inflammatory activity in multiple sclerosis (MS) and provides a sensitive means of monitoring immunomodulatory therapies in exploratory trials. Serial monthly studies were performed in eight relapsing-remitting and eight secondary progressive patients to assess new and more sensitive techniques for enhanced MRI. Brain and spine imaging was carried out at 1.5-T on two occasions 24-72 h apart using a conventional imaging protocol with T1-weighted MRI at single-dose (0.1 mmol/kg) Gd-DTPA and a potentially more sensitive "modified" protocol with T1-weighted MRI at triple-dose (0.3 mmol/kg) Gd-DTPA (with addition of delay and magnetisation transfer presaturation for brain imaging). For each MRI protocol the total numbers of enhancing lesions (97 paired studies) and new enhancing lesions (81 paired studies) were assessed. The total number of enhancing lesions seen was 347/75 on conventional brain/cord MRI respectively, and 754/123 on modified brain/cord MRI. The respective numbers of new enhancing lesions were 168/40 on conventional and 276/71 on modified scans. Smaller increases were seen in the proportion of active scans using the modified protocol. Sample size calculations showed no reduction in sample sizes required for a parallel group study but a reduced sample size for crossover studies using the modified protocol; the addition of cord to brain imaging did not improve power for either trial design. A combined modified brain and cord imaging protocol markedly improves the detection of areas of focal BBB leakage in MS and may be useful in selected natural history studies. The modified brain protocol reduces sample size requirements for crossover studies but not necessarily for parallel design trials.

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MRI readily detects the lesions of multiple sclerosis (MS) in the brain and spinal cord. Conventional MRI sequences do not, however, permit distinction between the various pathological characteristics (oedema, demyelination, axonal loss and gliosis) of lesions in MS. Magnetisation transfer (MT) imaging may be more specific in distinguishing the pathologies responsible for disability in MS, namely demyelination and axonal loss, and therefore may have a potential role in monitoring treatment. We have applied MT imaging to the cervical spinal cord to see if it is feasible to measure MT ratios (MTR) in this region where pathological changes may result in considerable disability. We studied 12 patients with MS and 12 age- and sex-matched normal controls using a sagittal T2-weighted fast spin-echo sequence with and without an MT pulse. The median value for cervical cord mean MTR measurement in normal controls was 19.30% units (interquartile range 19.05-19.55), whereas values were significantly lower in MS patients (median = 17.95% units, interquartile range 17.25-19.00, P = 0.0004). There was a low intrarater variability for repeated mean MTR measurements. We conclude that it is possible to measure MTR in the cervical spinal cord, that a significant reduction occurs in patients with MS, and that there may be a role for this measure in future MS treatment trials.