Doctor's Review: Medicine on the Move

December 17, 2017

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Many buildings in New Orleans' French Quarter date back to its days as a French colony.

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Conference proceedings: Meeting of the American Academy of Neurology

A jambalaya of nervous conditions

Medical conferences don't come much bigger — or longer — than the seven-day jamboree that is the 64th annual scientific meeting of the American Academy of Neurology (AAN), which this past April descended upon the still-recovering city of New Orleans.

Neurology is arguably a host of medical specialities masquerading as one and its leading conference reflects this multifaceted character. It was spread across multiple venues: the Hilton, the Marriott, the Ernest N. Morial Convention Center and some offsite locations.

Countless satellite meetings siphoned delegates away from the main event, especially the one-and-a-half day 'Subspeciality in Focus' programs, six events which mix the latest science with advanced education for those who want to go further down one of neurology's many winding alleys. This year the six programs were peripheral nerve disorders, ageing/dementia/degenerative disease, cerebrovascular disease, epilepsy, movement disorders and child neurology.

Keeping migraine at bay

We've learned as much about preventing migraine as we have about treating it in the past decade, but while new treatments have turned around the lives of many sufferers, the lessons learned in prevention are rarely put into practice. Only 3 to 13 percent of migraineurs take steps to reduce the frequency and severity of attacks, while the evidence suggests that nearly half would benefit. Only new guidelines can spread the word and these were proclaimed at New Orleans.

“The strongest evidence we found was for the pharmaceutical treatments divalproex sodium, sodium valproate, topiramate, metoprolol, propranolol and timolol, and for frovatriptan in short-term menstrually-associated migraine, as well as for the herbal preparation Petasites (butterbur),” said guideline author Dr Stephen D. Silberstein. Indeed, butterbur earned the same class A recommendation as the beta-blockers and the potent seizure drugs. The practitioner who prescribes any of these to prevent or mitigate future attacks does so with the blessing of the American Academy of Neurology and the American Headache Society.

Less certain evidence suggested a probable preventive effect from the NSAIDs fenoprofen, ibuprofen, ketoprofen and naproxen. Also getting the half-nod was subcutaneous histamine and the complementary treatments magnesium, feverfew and riboflavin. “Some studies show that migraine attacks can be reduced by more than half with preventive treatments,” Silberstein noted. But lamotrigine, an anticonvulsant once thought to hold promise in migraine prevention, has now been weighed in the balance and found wanting. Incidentally, among migraine treatments (not preventive agents), the AAN still recommends against one recently approved by Health Canada: botulinum toxin.

Can we nip MS in the bud?

AAN members were more enthusiastic, however, about one treatment approved in Canada that's not available in the US. The human serum albumin-free formulation of interferon beta-1a — which is, in fact, approved almost everywhere in the world — appeared to reduce the likelihood of progression to clinically definite multiple sclerosis in people treated soon after a first demyelinating event.

The phase three results of the three-year REFLEXION clinical trial were presented by Dr Mark Freedman of the University of Ottawa. The 517 participants, in addition to having a suggestive symptom such as muscle weakness or optic neuritis, each had at least two clinically silent brain lesions detected by MRI. Technically, this isn't even enough for an official diagnosis of MS, but caution in diagnosis is increasingly at odds with aggression in early treatment. “While we’ve known it’s beneficial to start MS drugs as soon as possible, this is the first trial to show a benefit of early injections of interferon beta-1a treatment at three years,” said Dr Freedman.

Of those who received 44 micrograms thrice weekly, starting an average 53 days after first symptoms, 27 percent had progressed to clinically definite MS at three years, compared to 41 percent of those taking placebo. A third group received the same 44 micrograms once a week — an unapproved dosage — and only 28 percent of these progressed to clinically definite disease. This might seem to hold out the promise of far cheaper interferon treatment, but Dr Freedman cautions that the McDonald criteria, which use MRI scans as well as clinical measures, tell a different story. “There were significantly more benefits in taking the drug three times a week when it came to brain lesion changes and other McDonald criteria,” he said. These criteria were met by 87 percent of placebo subjects, 79 percent of once-weekly interferon subjects and 67 percent of thrice-weekly subjects.

There was no shortage of new and experimental MS treatments presented in New Orleans, including studies of dimethyl fumarate, a monoclonal antibody called daclizumab HYP, another called alemtuzumab, the CNS immunomodulator laquinimod and an investigational oral drug called ONO-4641. To make a long story very short, some of the results were pretty dramatic, but so were some of the side effects. Overall, there's a promise of markedly greater efficacy than today's rather anemic MS armamentarium, but also perhaps a rougher road ahead in terms of compliance and tolerability.

A drug that makes no sense

Common sense dictates that taking antibodies from the blood of pooled donors and injecting them into people with overactive immune systems should set off a veritable firestorm of inflammation, but for completely unknown reasons intravenous immune globulin (IVIg) appears to do the exact opposite, quieting many autoimmune diseases. A new AAN guideline finds it as useful as plasma exchange in treating Guillain-Barré syndrome (GBS). It's also effective in moderate to severe myasthenia gravis, chronic inflammatory demyelinating polyneuropathy (CIDP) and some rarer neuromuscular conditions. And in common with so many new neurological treatments, it carries a jaw-dropping price tag. Perhaps we should bow to the inevitable and equip every neurology ward with an executive lounge.

Who gets what

New Orleans presented a smorgasbord of epidemiological data. Much of it confirmed recent suspicions, for example the growing certainty that physical activity is beneficial in Parkinson's and that weight training outperforms fitness programs. The mountain of evidence that shows mental activity staving off dementia grew a little higher and physical activity too appears protective against Alzheimer's. Poor sleep is predictive of dementia, as is slow gait and weak grip around age 60. Overeating in old age dramatically increases the risk of cognitive decline. Maternal migraine is associated with infant colic, which in turn can be a precursor of childhood periodic syndrome, which often grows into adult migraine.

More unexpected was the finding that Hispanics born outside the US are 42 percent less likely than non-Hispanic whites of similar income and education to suffer a first stroke — and hold the same advantage over Hispanics born in the US. Is this gaping difference down to pollution, diet, or perhaps family support networks? Maybe next year's meeting will reveal the answer.

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