We strongly recommend the use of prochlorperazine based on a high level of evidence, lysine acetylsalicylic acid, metoclopramide and sumatriptan, based on a moderate level of evidence, and ketorolac, based on a low level of evidence. We weakly recommend the use of chlorpromazine based on a moderate level of evidence, and ergotamine, dihydroergotamine, lidocaine intranasal and meperidine, based on a low level of evidence. We found evidence to recommend strongly against the use of dexamethasone, based on a moderate level of evidence, and granisetron, haloperidol and trimethobenzamide based on a low level of evidence. Based on moderate-quality evidence, we recommend weakly against the use of acetaminophen and magnesium sulfate. Based on low-quality evidence, we recommend weakly against the use of diclofenac, droperidol, lidocaine intravenous, lysine clonixinate, morphine, propofol, sodium valproate and tramadol.

Menstrually related migraine (MRM) headache is common in women and associated with substantial disability. Compared to nonmenstrual migraine, MRM attacks are more severe, longer in duration, and have a poorer response to analgesics. The purpose of this guideline is to provide a systematic review and meta-analysis of the existing therapy trials for MRM and evidence-based recommendations for acute and short-term preventive treatment of MRM headache. Prospective, double-blind, randomized controlled trials of any pharmacologic agent for the symptomatic relief or prevention of MRM headache were included in the guideline. The main outcomes considered were the pain response and pain-free response at 2 hours for acute treatment trials, and the incidence of MRM or the number of days on which MRM attacks occurred for short-term prevention trials. Nineteen trials were included in the analysis. The US Preventive Services Task Force quality criteria were used to assess trial quality and to grade recommendations. Based on the evidence, grade B recommendations can be made for the use of sumatriptan 50 and 100 mg, mefenamic acid 500 mg, and rizatriptan 10 mg for the acute treatment of MRM. For the preventive treatment of MRM, there are grade B recommendations for the perimenstrual use of transcutaneous estrogen 1.5 mg, frovatriptan 2.5 mg twice daily, and naratriptan 1 mg twice daily. Choosing among treatment strategies must be based on clinical considerations.

Results demonstrate that the frequency of mutations found in Krit1 is 47% in the families studied and the frequency may increase as more mutations are detected. Mutations are evenly distributed in the gene and do not seem to be limited to structural domains present in Krit1. This is in accordance with the model that Krit1 could be a tumor suppressor gene.

Key points• The choice of prophylactic therapy for migraine is based on existing comorbidities, contraindications, reported efficacy, and adverse effect profiles.• Prophylaxis should be considered for patients whose migraines affect their quality of life despite appropriate symptomatic treatment, or who are at risk for medication overuse headache.• The period that successful migraine prophylaxis should be continued is not clear; patients should be followed up regularly to ensure that their medication is still beneficial.

The "Acute Treatment of Migraine in Adults: The American Headache Society Evidence Assessment of Migraine Pharmacotherapies" provides levels of evidence for medication efficacy for acute treatment of migraine. The goal of this companion paper is to provide guidance on how to choose between evidence-based treatment options, and, based on the clinical characteristics of the patient and their migraine attacks, to provide guidance on designing an individualized strategy for managing migraine attacks. The acute pharmacological treatments described in the American Headache Society evidence assessment can be divided into those initially taken by the patient during the headache phase of the migraine attack, those taken by the patient later in the attack when initial treatments fail, and those administered intravenously or intramuscularly in urgent care settings. Medications taken initially by patients in the headache phase include nonspecific analgesics such as acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), triptans, and dihydroergotamine (DHE). A stratified approach to treatment is advised, with the choice of medication based on the patient's treatment needs, taking into consideration the attack severity, presence of associated symptoms such as nausea and vomiting, and the degree of migraine-related disability. Individuals with migraine may find reassurance in having a "back-up plan" in the event of an initial acute treatment failure. For those individuals who had a partial response to the initial acute treatment, a second dose might be indicated. When the initial treatment does not provide meaningful and sustained benefits, a treatment from a different medication class is typically chosen. Depending upon the initial treatment used, this might include NSAIDs, triptans, or DHE. Opioids or acetaminophen in combination with codeine or tramadol can be considered as part of the "back-up plan," provided they are used infrequently. When all patient administered treatments have failed and moderate to severe migraine symptoms remain, some individuals seek treatment in urgent care settings. The intravenous administration of antiemetics with or without an intravenous or intramuscular NSAID or DHE, or an intramuscular opioid can be considered. Patients with migraine should be encouraged to treat migraine pain early, and avoid overuse of medications.

Cerebral cavernous malformations (CCM) are vascular anomalies, sometimes inherited as an autosomal dominant trait, which can cause strokes and seizures. Recently, mutations of the CCM1 gene (chromosome 7q) have been found in a subset of families. The authors found 10 new mutations by screening 29 families and five seemingly sporadic cases of CCM. The mutations predicted truncation of the Krit1 mRNA encoded by CCM1, supporting the contention that CCM result from loss of Krit1 protein function and the possibility that this protein acts as a tumor suppressor.

Background:The chronic cerebrospinal venous insufficiency theory proposes that altered cerebral venous hemodynamics play a role in the pathophysiology of multiple sclerosis. We aimed to explore the validity of this hypothesis by assessing the diagnostic criteria for chronic cerebrospinal venous insufficiency in persons with and without multiple sclerosis. Methods:We compared the proportion of venous outflow abnormalities between patients with multiple sclerosis and healthy controls using extracranial Doppler ultrasonography and gadolinium-enhanced magnetic resonance venography. Interpreting radiologists were blinded to the clinical status of participants. Results:We enrolled 120 patients with multiple sclerosis and 60 healthy controls. High proportions of both patients (67/115 [58%]) and controls (38/60 [63%]) met 1 or more of the proposed ultrasound criteria for diagnosis of chronic cerebrospinal venous insufficiency (p = 0.6). A minority of patients (23/115 [20%]) and controls (6/60 [10%]) fulfilled 2 or more of the proposed criteria (p = 0.1). There were no differences between patients and controls in the prevalence of each individual ultrasound criterion. Similarly, there were no differences in intracranial or extracranial venous patency between groups, as measured by magnetic resonance venography. Interpretation:We detected no differences in the proportion of venous outflow abnormalities between patients with multiple sclerosis and healthy controls. Moreover, our study revealed significant methodologic concerns regarding the proposed diagnostic criteria for chronic cerebrospinal venous insufficiency that challenge their validity. AbstractResearch CMAJ, August 5, 2014, 186(11) E419

As a result of the recent literature, clinicians can feel comfortable treating children with co-morbid attention deficit hyperactivity disorder and Tourette syndrome with stimulant medications. It has also been established that transient tics are very common in children, and for the most part, non-disabling. In those children with persistent tics, behavioural disorders are associated which may impair success in school and psychosocial functioning. Clinicians have a number of therapeutic options, with recent double-blinded randomized trials of clonidine, risperidone, and desipramine showing benefit. Scientists continue to search for the cause of Tourette syndrome.