Central Pontine Myelinolysis and Localized Fluorodeoxyglucose Uptake Seen on 18F-FDG PET/CT.

Case report describing the finding of central pontine myelinolysis (CPM) using combined fluorine-18 ( 18F)-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). The patient was a known alcoholic who, during admission was under treatment for hyponatremia, showed a significant decline in both motor and cognitive function. Combined 18F-FDG PET/CT showed localized FDG uptake in the pons, consistent with the finding of CPM observed on magnetic resonance imaging (MRI). CPM is a demyelinating lesion of the pons, resulting in several neurological symptoms. The exact cause of CPM is not clear, but a strong relations between loss of myelin and osmotic stress exists, especially during rapid correction of hyponatremia. The osmotic stress is thought to induce disruption of the blood-brain barrier, allowing access for inflammatory mediators in extravascular brain tissue, which most likely attracts glial cells of the brain, attracts macrophages and activates astocytes. We suggest that metabolism in these activated cells could be responsible for the localized FDG uptake during active CPM.

Delayed absorption of many (paracetamol, aspirin, other NSAIDs and zolmitriptan) but not all (sumatriptan, rizatriptan) drugs during migraine attacks and most likely normal gastric emptying outside attacks. A review.

Background In most pharmacokinetic studies, the oral absorption of drugs is impaired during migraine attacks but exceptions occur. A study on gastric emptying using gastric scintigraphy indicated that gastric stasis also occurs interictally in migraine. These studies were reviewed critically. Results In seven studies, mainly investigating NSAIDs and analgesics, the early absorption of the drugs during 112 migraine attacks was delayed. The absorption of sumatriptan is usual in therapeutic doses, and rizatriptan was normal during 131 migraine attacks. The interictal gastric stasis observed using gastric emptying scintigraphy (GES) with solids ( n = 13) could not be confirmed in a larger study ( n = 27) using the same method. Also gastric emptying measured with GES with liquids ( n = 7) and epigastric impedance ( n = 64) was normal outside migraine attacks. Conclusions and possible clinical implications Drug absorption is not generally impaired during migraine attacks. Gastric emptying is most likely normal in the majority of migraine patients outside attacks. Prokinetic and antiemetic drugs such as metoclopramide and domperidone should not be routinely combined with oral analgesics or oral triptans. If, however, nausea is severe or vomiting occurs, treatment with an antiemetic with proven efficacy on the nausea of migraine can be indicated.

Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards subcommittee of the American Academy of Neurology and the American Headache Society.

Peer Carsten Tfelt-Hansen, Glostrup, Denmark: According to the recent American Academy of Neurology (AAN) guideline update, a drug can be recommended as possibly effective for migraine prevention if it had demonstrated efficacy in one Class II study.(1) Eight drugs are recommended as possibly effective,(1) and there are several drugs for which I would question the evidence. Due to space limitations, I have chosen just one example.

CONSORT recommendations in abstracts of randomised, controlled trials on migraine and headache.

A CONSORT statement on the content of abstracts of randomised, controlled trials (RCTs) was published in 2008. I therefore reviewed the abstracts from 2009 to 2010 published on RCTs in Cephalalgia, Headache and other (non-headache) journals. The following items were reviewed: number of patients, reporting of response either in percentages or absolute values, the use of p values, and effect size with its precision. The latter was recommended in the CONSORT statement. A total of 46 abstracts were reviewed and effect size with 95% confidence intervals was only reported in seven abstracts. The influence of the CONSORT statement on reporting in abstracts has so far only had a limited influence on the headache literature.

Published and not fully published double-blind, randomised, controlled trials with oral naratriptan in the treatment of migraine: a review based on the GSK Trial Register.

Naratriptan 2.5 mg is now an over-the-counter drug in Germany. This should increase the interest in drug. The GSK Trial Register was searched for published and unpublished double-blind, randomised, controlled trials (RCTs) concerning the use of naratriptan in migraine. Only 7 of 17 RCTs are published in full. Naratriptan 2.5 mg is superior to placebo for acute migraine treatment in 6 RCTs, but inferior to sumatriptan 100 mg and rizatriptan 10 mg in one RCT each. This dose of naratriptan has no more adverse events than placebo. Naratriptan 1 mg b.i.d. has some effect in the short-term prophylactic treatment of menstruation-associated migraine in 3 RCTs. In 2 RCTs, naratriptan 2.5 mg was equivalent to naproxen sodium 375 mg for migraine-related quality of life. Naratriptan 2.5 mg (34% preference) was superior to naproxen sodium 500 mg (25% preference). Naratriptan 2.5 mg is better than placebo in the acute treatment of migraine. The adverse effect profile of naratriptan 2.5 mg is similar to that of placebo. The efficacy of naratriptan 2.5 mg versus NSAIDs is not sufficiently investigated. Naratriptan, when available OTC is a reasonable second or third choice on the step care ladder in the acute treatment of migraine.

Permeability of dura mater: a possible link between cortical spreading depression and migraine pain? A comment.

In the wake of cortical spreading depression (CSD) it has been suggested that noxious substances diffuse through the dura with resulting firing of epidural nerves. In my view this is unlikely because there are good reasons to suggest that there must be a dura-brain barrier. Alternatively collateral branches from the trigeminal nerve to the pia and the dura may signal what is happening with ions and substances on the brain surface during CSD to the epidural space.

Verisimilitude (or "truthlikeness") as an alternative to pro and cons: migraine and cluster headache mechanisms.

Calculating verisimilitude (or "truthlikeness") ad modum Popper is a quantitative alternative to the usual pros and cons in migraine and cluster headache mechanisms. The following items were evaluated: dilation of large cranial arteries during migraine; CGRP increase during migraine; migraine as a brain disorder; aura and migraine headache; brain stem activation during migraine; rCBF in migraine without aura; NO and pathophysiology of migraine; neurogenic inflammation and migraine; aura in cluster headache; and hypothalamic activation in cluster headache. It is concluded that verisimilitude calculations can be helpful when judging pathophysiological problems in migraine and cluster headache.

Does sumatriptan cross the blood-brain barrier in animals and man?

Sumatriptan, a relatively hydrophilic triptan, based on several animal studies has been regarded to be unable to cross the blood-brain barrier (BBB). In more recent animal studies there are strong indications that sumatriptan to some extent can cross the BBB. The CNS adverse events of sumatriptan in migraine patients and normal volunteers also indicate a more general effect of sumatriptan on CNS indicating that the drug can cross the BBB in man. It has been discussed whether a defect in the BBB during migraine attacks could be responsible for a possible central effect of sumatriptan in migraine. This review suggests that there is no need for a breakdown in the BBB to occur in order to explain a possible central CNS effect of sumatriptan.