How to do it: investigate exertional rhabdomyolysis (or not).

Rhabdomyolysis is the combination of symptoms (myalgia, weakness and muscle swelling) and a substantial rise in serum creatine kinase (CK) >50 000 IU/L; there are many causes, but here we specifically address exertional rhabdomyolysis. The consequences of this condition can be severe, including acute kidney injury and requirement for higher level care with organ support. Most patients have 'physiological' exertional rhabdomyolysis with no underlying disease; they do not need investigation and should be advised to return to normal activities in a graded fashion. Rarely, exertional rhabdomyolysis may be the initial presentation of underlying muscle disease, and we review how to identify this much smaller group of patients, who do require investigation.

Clinicopathological case: progressive somnolence and dementia in an accountant: when the shine rubs off the gold standard.

A 63-year-old accountant developed progressive somnolence, cognitive decline, gait disturbance and cerebellar dysfunction with autonomic features. This report documents the clinicopathological conference at the 39th Edinburgh Advanced Neurology Course 2017.

National survey of UK medical students on the perception of neurology.

BACKGROUND: Medical students perceive neurology to be a difficult subject, a phenomenon described as "neurophobia". Studies investigating student attitudes towards neurology have so far been limited by small sample sizes as a consequence of being conducted within a single medical school or region. We aimed to conduct the first national survey of the perception of neurology among UK medical students. METHODS: A 24 question online survey was designed and distributed in the form of a web-link to all UK medical schools. Responses were collected for 10 weeks with reminders sent at 3 and 6 weeks. A prize-draw of £300 was offered upon completion of the survey. RESULTS: 2877 medical students from 25 of 31 medical schools responded. Students found neurology to be significantly more difficult than other specialties and were least comfortable drawing up a neurological differential diagnosis compared to other specialties (p < 0.0001 for neurology vs. each of the other specialties). Neuroanatomy was regarded as the most important factor contributing to neurology being perceived as difficult. CONCLUSIONS: The findings of the first national survey addressing this issue are consistent with previous research. The perception of neurology remains unchanged, in contrast to the rapidly changing demands of neurological care in an ageing population. Neurological examination and formulating a differential diagnosis are important skills in any medical specialty, and combatting "neurophobia" in medical students is therefore essential.

Screening patients with a family history of subarachnoid haemorrhage for intracranial aneurysms: screening uptake, patient characteristics and outcome.

BACKGROUND AND PURPOSE: People with one or more first degree relative affected (FDRA) by aneurysmal subarachnoid haemorrhage (aSAH) are at a higher lifetime risk of an aSAH than those without a family history. Screening may be worthwhile for people with two or more FDRA by aSAH. Little is known about the characteristics of people with a family history of aSAH who undergo screening in clinical practice. METHODS: Observational analysis of consecutive attendances at an intracranial aneurysm screening clinic. RESULTS: Of 96 adults seen, 19 did not have a family history of aSAH and 77 had one or more FDRA by aSAH: 35 had two or more FDRA, 21 had one FDRA plus one or more affected second degree relative and 21 had one FDRA only. In these three respective groups, 29 (83%), 15 (71%) and five (24%) adults underwent screening, of whom six (21%), two (13%) and one (20%) had an aneurysm detected (p=0.5). Of the nine patients with aneurysms, four underwent treatment. Considering other risk factors, adults with two or more FDRA were more likely to be hypertensive (OR 3.3, 95% CI 1.0 to 10.8; p=0.046) but were no more likely to smoke or drink to excess than adults with one FDRA. Adults who underwent screening were more likely to be hypertensive and drink alcohol to excess (both p=0.03), but were no more likely to smoke than those who were not screened. CONCLUSIONS: In clinical practice, people undergoing intracranial aneurysm screening had stronger family histories of aSAH and they were also more likely to have modifiable risk factors for aSAH.

Autoimmune limbic encephalitis.

Autoimmune limbic encephalitis is an increasingly recognised cause of cognitive decline and confusion. The typical presentation is with subacute cognitive decline, behavioural disturbance and seizures. Magnetic resonance imaging may show characteristic changes in the medial temporal regions. The diagnosis is confirmed by identification of elevated voltage-gated potassium channel antibody (VGKC-Ab) titres. It is a highly treatable condition, often responding well to intravenous immunoglobulin or steroids. Recognition of autoimmune limbic encephalitis is sometimes delayed--usually because the diagnosis has not been considered--which can result in long-term neurological consequences.

Experiences of remote consulting for patients and neurologists during the COVID-19 pandemic in Scotland.

BACKGROUND: Remote consulting is an emerging model in managing chronic neurological conditions and has been widely implemented during the COVID-19 pandemic. The objective of this national survey was to investigate the initial experiences of remote consulting for neurologists and patients with established neurological conditions under follow-up during the first COVID-19 phase. METHODS: In collaboration with the Scottish Association of Neurological Sciences and the Neurological Alliance of Scotland, we conducted a web-based survey of neurologists and patients between October and November 2020. FINDINGS: Data was available for 62 neurologists and 201 patients. The consensus among neurologists was that remote consulting is a satisfactory way of delivering healthcare in selected groups of patients. For practical and technical reasons, there was preference for phone over video consultations (phone 63% vs video 33%, p=0.003). The prevailing opinion among clinicians was that considerable training interventions for remote consultation skills are required ('yes' 63% vs 'no' 37%, p=0.009) to improve clinician consultation skills and successfully embed this new model of care.Most patients perceived remote consultations as safe, effective and convenient, with 89% of patients being satisfied with their remote consultation experience. Although traditional face-to-face consultations were the favoured way of interaction for 62% of patients, a significant proportion preferred that some of their future consultations be remote. INTERPRETATION: Although not a replacement for face-to-face consultations, this survey illustrates that remote consulting can be an acceptable adjunct to traditional face-to-face consultations for doctors and patients. More research is required to identify overall safety and applicability.

Early treatment with prednisolone or acyclovir in Bell's palsy.

BACKGROUND: Corticosteroids and antiviral agents are widely used to treat the early stages of idiopathic facial paralysis (i.e., Bell's palsy), but their effectiveness is uncertain. METHODS: We conducted a double-blind, placebo-controlled, randomized, factorial trial involving patients with Bell's palsy who were recruited within 72 hours after the onset of symptoms. Patients were randomly assigned to receive 10 days of treatment with prednisolone, acyclovir, both agents, or placebo. The primary outcome was recovery of facial function, as rated on the House-Brackmann scale. Secondary outcomes included quality of life, appearance, and pain. RESULTS: Final outcomes were assessed for 496 of 551 patients who underwent randomization. At 3 months, the proportions of patients who had recovered facial function were 83.0% in the prednisolone group as compared with 63.6% among patients who did not receive prednisolone (P<0.001) and 71.2% in the acyclovir group as compared with 75.7% among patients who did not receive acyclovir (adjusted P=0.50). After 9 months, these proportions were 94.4% for prednisolone and 81.6% for no prednisolone (P<0.001) and 85.4% for acyclovir and 90.8% for no acyclovir (adjusted P=0.10). For patients treated with both drugs, the proportions were 79.7% at 3 months (P<0.001) and 92.7% at 9 months (P<0.001). There were no clinically significant differences between the treatment groups in secondary outcomes. There were no serious adverse events in any group. CONCLUSIONS: In patients with Bell's palsy, early treatment with prednisolone significantly improves the chances of complete recovery at 3 and 9 months. There is no evidence of a benefit of acyclovir given alone or an additional benefit of acyclovir in combination with prednisolone. (Current Controlled Trials number, ISRCTN71548196 [controlled-trials.com].).

Blocking alpha4-integrins - A small molecule approach to treatment of multiple sclerosis.

Inhibition of leukocyte trafficking using antibody blockade of the alpha4 (alpha4)-integrins has now been validated as a therapeutic approach for the treatment of multiple sclerosis (MS). This positive validation has led to the discovery of small molecule alpha4 antagonists that are progressing through clinical trials. The challenges in development of these antagonists will be discussed along with a clinical update on the most advanced candidates.

Imidazopyridines as VLA-4 integrin antagonists.

We describe a novel series of imidazopyridine substituted phenylalanines which are potent VLA-4 antagonists. A wide variety of substituents are tolerated as replacements for the pendant 3-pyridyl ring. A clear structure-activity relationship was identified around the substitution of the 3-amino-cyclobut-2-enone portion of the molecule.

Synthesis and structure-activity relationship of aminopyrimidine IKK2 inhibitors.

The synthesis and structure-activity relationship of a novel series of aminopyrimidines are exemplified. Results of key compounds from within this series in the E-selectin reporter cell assay are also reported.

Alpha4-integrin antagonism--an effective approach for the treatment of inflammatory diseases?

Inhibition of leucocyte trafficking by antagonism of the alpha4 (alpha4)-integrin has now been validated as a therapeutic approach for the treatment of inflammatory diseases such as multiple sclerosis (MS) and inflammatory bowel disease (IBD). This validation has been overshadowed by three incidences of progressive multifocal leucoencaphalopathy (PML) in patients receiving natalizumab (Tysabri), a therapeutic monoclonal IgG antibody directed against alpha4-integrins. This led to the initial removal of natalizumab from the market. Following a safety review, it was reintroduced for the treatment of relapsing-remitting MS patients (with restrictions). This has led to a refocus on alpha4-integrins as a therapeutic target across the pharmaceutical industry. Recent advances in small molecule development are worth reviewing. New understanding of pharmacokinetics and selectivity will potentially contribute to the development of alpha4 antagonist with greater clinical efficacy and safety.