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The primary objective of this guideline is to assist the practitioner in choosing an appropriate acute medication for an individual with migraine, based on current evidence in the medical literature and expert consensus. It is focused on patients with episodic migraine (headache on < 14 days a month).
A detailed search strategy was used to find relevant meta-analyses, systematic reviews and randomized double-blind controlled trials. Recommendations were graded with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group, using a consensus group. In addition, a general literature review and expert consensus were used for aspects of acute therapy for which randomized controlled trials are not available.
Twelve acute medications received a strong recommendation for use in acute migraine therapy (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan, ASA, ibuprofen, naproxen sodium, diclofenac potassium, and acetaminophen). Four received a weak recommendation for use (dihydroergotamine, ergotamine, codeine-containing combination analgesics, and tramadol-containing combination analgesics). Three of these were NOT recommended for routine use (ergotamine, and codeine- and tramadol-containing medications). Strong recommendations were made to avoid use of butorphanol and butalbital-containing medications. Metoclopramide and domperidone were strongly recommended for use where necessary. Our analysis also resulted in the formulation of eight general acute migraine treatment strategies. These were grouped into: 1) two mild-moderate attack strategies, 2) two moderate-severe attack or NSAID failure strategies, 3) three refractory migraine strategies, and 4) a vasoconstrictor unresponsive-contraindicated strategy. Additional strategies were developed for menstrual migraine, migraine during pregnancy, and migraine during lactation.
This guideline provides evidence-based advice on acute pharmacological migraine therapy, and should be helpful to both health professionals and patients. The available medications have been organized into a series of strategies based on patient clinical features. These strategies may help practitioners make appropriate acute medication choices for patients with migraine.
Dravet syndrome is among the most challenging electroclinical syndromes. There is a high likelihood of recurrent status epilepticus; seizures are medically refractory; and patients have multiple co-morbidities, including intellectual disability, behaviour and sleep problems, and crouch gait. Additionally, they are at significant risk of sudden unexplained death. This review will focus predominantly on the prophylactic medical management of seizures, addressing both first-line therapies (valproate and clobazam) as well as second-line (stiripentol, topiramate, ketogenic diet) or later options (levetiracetam, bromides, vagus nerve stimulation). Sodium channel agents—including carbamazepine, oxcarbazepine, phenytoin and lamotrigine—should be avoided, as they typically exacerbate seizures. Several agents in development may show promise, specifically fenfluramine and cannabidiol, but they need further evaluation in randomized, controlled trials. In addition to prophylactic treatment, all patients need home-rescue medication and a status epilepticus protocol that can be carried out in their local hospital. Families must be counselled on non-pharmacologic strategies to reduce seizure risk, including avoidance of triggers that commonly induce seizures (including hyperthermia, flashing lights and patterns). In addition to addressing seizures, holistic care for a patient with Dravet syndrome must involve a multidisciplinary team that includes specialists in physical, occupational and speech therapy, neuropsychology, social work and physical medicine.
Cerebral vasospasm is a prolonged but reversible narrowing of cerebral arteries beginning days after subarachnoid hemorrhage. Progression to cerebral ischemia is tied mostly to vasospasm severity, and its pathogenesis lies in artery encasement by blood clot, although the complex interactions between hematoma and surrounding structures are not fully understood. The delayed onset of vasospasm provides a potential opportunity for its prevention. It is disappointing that recent randomized, controlled trials did not demonstrate that the endothelin antagonist clazosentan, the cholesterol-lowering agent simvastatin, and the vasodilator magnesium sulfate improve patient outcome. Minimizing ischemia by avoiding inadequate blood volume and pressure, administering the calcium antagonist nimodipine, and intervention with balloon angioplasty, when necessary, constitutes current best management. Over the past two decades, our ability to manage vasospasm has led to a significant decline in patient morbidity and mortality from vasospasm, yet it still remains an important determinant of outcome after aneurysm rupture.
The Milwaukee protocol has been attributed to survival in rabies encephalitis despite a lack of scientific evidence supporting its therapeutic measures. We have reviewed the literature with reference to specific treatment recommendations made within the protocol. Current literature fails to support an important role for excitotoxicity and cerebral vasospasm in rabies encephalitis. Therapies suggested in the Milwaukee protocol include therapeutic coma, ketamine infusion, amantadine, and the screening/prophylaxis/management of cerebral vasospasm. None of these therapies can be substantiated in rabies or other forms of acute viral encephalitis. Serious concerns over the current protocol recommendations are warranted. The recommendations made by the Milwaukee protocol warrant serious reconsideration before any future use of this failed protocol.
Updated information on the epidemiology of dementia due to Alzheimer’s disease (AD) is needed to ensure that adequate resources are available to meet current and future healthcare needs. We conducted a systematic review and meta-analysis of the incidence and prevalence of AD.
The MEDLINE and EMBASE databases were searched from 1985 to 2012, as well as the reference lists of selected articles. Included articles had to provide an original population-based estimate for the incidence and/or prevalence of AD. Two individuals independently performed abstract and full-text reviews, data extraction and quality assessments. Random-effects models were employed to generate pooled estimates stratified by age, sex, diagnostic criteria, location (i.e., continent) and time (i.e., when the study was done).
Of 16,066 abstracts screened, 707 articles were selected for full-text review. A total of 119 studies met the inclusion criteria. In community settings, the overall point prevalence of dementia due to AD among individuals 60+ was 40.2 per 1000 persons (CI95%: 29.1-55.6), and pooled annual period prevalence was 30.4 per 1000 persons (CI95%: 15.6-59.1). In community settings, the overall pooled annual incidence proportion of dementia due to AD among individuals 60+ was 34.1 per 1000 persons (CI95%: 16.4-70.9), and the incidence rate was 15.8 per 1000 person-years (CI95%: 12.9-19.4). Estimates varied significantly with age, diagnostic criteria used and location (i.e., continent).
The burden of AD dementia is substantial. Significant gaps in our understanding of its epidemiology were identified, even in a high-income country such as Canada. Future studies should assess the impact of using such newer clinical diagnostic criteria for AD dementia such as those of the National Institute on Aging–Alzheimer’s Association and/or incorporate validated biomarkers to confirm the presence of Alzheimer pathology to produce more precise estimates of the global burden of AD.
Population-based prevalence and incidence studies are essential for understanding the burden of frontotemporal dementia (FTD).
The MEDLINE and EMBASE databases were searched to identify population-based publications from 1985 to 2012, addressing the incidence and/or prevalence of FTD. References of included articles and prior systematic reviews were searched for additional studies. Two reviewers screened all abstracts and full-text reviews, abstracted data and performed quality assessments.
Twenty-six studies were included. Methodological limitations led to wide ranges in the estimates for prevalence (point prevalence 0.01-4.6 per 1000 persons; period prevalence 0.16-31.04 per 1000 persons) and incidence (0.0-0.3 per 1000 person-years). FTD accounted for an average of 2.7% (range 0-9.1%) of all dementia cases among prevalence studies that included subjects 65 and older compared to 10.2% (range 2.8-15.7%) in studies restricted to those aged less than 65. The cumulative numbers of male (373 [52.5%]) and female (338 [47.5%]) cases from studies reporting this information were nearly equal (p=0.18). The behavioural variant FTD (bvFTD) was almost four times as common as the primary progressive aphasias.
Population-based estimates for the epidemiology of FTD varied widely in the included studies. Refinements in the diagnostic process, possibly by the use of validated biomarkers or limiting case ascertainment to specialty services, are needed to obtain more precise estimates of the prevalence and incidence of FTD.
Background: The timing of the circulatory determination of death for organ donation presents a medical and ethical challenge. Concerns have been raised about the timing of electrocerebral inactivity in relation to the cessation of circulatory function in organ donation after cardio-circulatory death. Nonprocessed electroencephalographic (EEG) measures have not been characterized and may provide insight into neurological function during this process. Methods: We assessed electrocortical data in relation to cardiac function after withdrawal of life-sustaining therapy and in the postmortem period after cardiac arrest for four patients in a Canadian intensive care unit. Subhairline EEG and cardio-circulatory monitoring including electrocardiogram, arterial blood pressure (ABP), and oxygen saturation were captured. Results: Electrocerebral inactivity preceded the cessation of the cardiac rhythm and ABP in three patients. In one patient, single delta wave bursts persisted following the cessation of both the cardiac rhythm and ABP. There was a significant difference in EEG amplitude between the 30-minute period before and the 5-minute period following ABP cessation for the group, but we did not observe any well-defined EEG states following the early cardiac arrest period. Conclusions: In a case series of four patients, EEG inactivity preceded electrocardiogram and ABP inactivity during the dying process in three patients. Further study of the electroencephalogram during the withdrawal of life sustaining therapies will add clarity to medical, ethical, and legal concerns for donation after circulatory determined death.
About one third of patients with epilepsy are pharmacoresistent. For a subgroup of this population, the ketogenic diet can be highly efficacious and should be considered early. This review discusses the different types of ketogenic diet, proposed mechanism of actions and its evidence for use in children and adults with both generalized and focal epilepsies where surgery is not feasible. In addition we discuss a practical approach to diet initiation, maintenance and monitoring for side effects. We also summarize the emerging evidence for the use of ketogenic diet in a broad range of neurological disorders.
Background: Epidemiologic studies have suggested that concussion, or mild traumatic brain injury (mTBI), is associated with a twofold or greater increase in relative risk for the development of post-traumatic epilepsy. To assess the clinical validity of these findings, we analyzed the incidence of epilepsy in a large cohort of post-concussion patients in whom concussion was strictly defined according to international guidelines. Methods: A retrospective cohort study of 330 consecutive post-concussion patients followed by a single concussion specialist. Exclusion criteria: abnormal brain CT/MRI, Glasgow Coma Scale<13 more than 1-hour post-injury, hospitalization >48 hours. Independent variable: concussion. Outcome measure: epilepsy incidence (dependent variable). Results: The mean number of concussions/patient was 3.3 (±2.5), mean age at first clinic visit 28 years (±14.7), and mean follow-up after first concussion 7.6 years (±10.8). Eight patients were identified whose medical records included mention of seizures or convulsions or epilepsy. Upon review by an epileptologist none met criteria for a definite diagnosis of epilepsy: four had episodic symptoms incompatible with epileptic seizures (e.g., multifocal paraesthesiae, multimodality hallucinations, classic migraine) and normal EEG/MRI investigations; four had syncopal (n=2) or concussive (n=2) convulsions. Compared with annual incidence (0.5/1000 individuals) in the general population, there was no difference in this post-concussion cohort (p=0.49). Conclusion: In this large cohort of post-concussion patients we found no increased incidence of epilepsy. For at least the first 5-10 years post-injury, concussion/mTBI should not be considered a significant risk factor for epilepsy. In patients with epilepsy and a past history of concussion, the epilepsy should not be presumed to be post-traumatic.
Because of a temporal correlation between the first notable signs and symptoms of autism and the routine childhood vaccination schedule, many parents have become increasingly concerned regarding the possible etiologic role vaccines may play in the development of autism. In particular, some have suggested an association between the Measles-Mumps-Rubella vaccine and autism. Our literature review found very few studies supporting this theory, with the overwhelming majority showing no causal association between the Measles-Mumps-Rubella vaccine and autism. The vaccine preservative thimerosal has alternatively been hypothesized to have a possible causal role in autism. Again, no convincing evidence was found to support this claim, nor for the use of chelation therapy in autism. With decreasing uptake of immunizations in children and the inevitable occurrence of measles outbreaks, it is important that clinicians be aware of the literature concerning vaccinations and autism so that they may have informed discussions with parents and caregivers.
Pompe disease is a lysosomal storage disorder caused by a deficiency of the enzyme acid alpha-glucosidase. Patients have skeletal muscle and respiratory weakness with or without cardiomyopathy. The objective of our review was to systematically evaluate the quality of evidence from the literature to formulate evidence-based guidelines for the diagnosis and management of patients with Pompe disease. The literature review was conducted using published literature, clinical trials, cohort studies and systematic reviews. Cardinal treatment decisions produced seven management guidelines and were assigned a GRADE classification based on the quality of evidence in the published literature. In addition, six recommendations were made based on best clinical practices but with insufficient data to form a guideline. Studying outcomes in rare diseases is challenging due to the small number of patients, but this is in particular the reason why we believe that informed treatment decisions need to consider the quality of the evidence.
Recent therapeutic advances in the management of multiple sclerosis (MS) have raised questions about the selection of appropriate patient candidates for various treatments and, if the plan is to move from one treatment to another, the appropriate sequencing of these therapies. The selected approach should provide optimal disease management without limiting future therapeutic options based on safety concerns, and recognize potential future treatments and the possibility of combination therapies. Additional challenges include incorporation of patient needs and preferences into the overall therapeutic approach, in order to ensure optimal outcomes in the short and long term. The objective of this manuscript is to provide an overview of what is currently known regarding the impact of various therapies for MS on future therapeutic choices (sequencing). In this context, we reviewed the available evidence in support of various treatments and, based on the presence of disease activity, suggested a scheme for switching or escalating therapy with the main focus on sequencing of therapeutic approaches.
Surface electroencephalogram (EEG) recording remains the gold standard for noninvasive assessment of electrical brain activity. It is the most efficient way to diagnose and classify epilepsy syndromes as well as define the localization of the epileptogenic zone. The EEG is useful for management decisions and for establishing prognosis in some types of epilepsy. Electroencephalography is an evolving field in which new methods are being introduced. The Canadian Society of Clinical Neurophysiologists convened an expert panel to develop new national minimal guidelines. A comprehensive evidence review was conducted. This document is organized into 10 sections, including indications, recommendations for trained personnel, EEG yield, paediatric and neonatal EEGs, laboratory minimal standards, requisitions, reports, storage, safety measures, and quality assurance.
Objective background: The Montreal Cognitive Assessment (MoCA) is a questionnaire that has been developed to help physicians around the world diagnose a patient’s cognitive ability. Available in multiple languages and for use in multiple countries worldwide, the goal of this study was to validate the alternate versions 2 and 3 of the French MoCA test to assist physicians in the detection of mild cognitive impairment (MCI), while decreasing the learning effect upon frequent testing. Methods: A validation study was conducted at the MoCA Clinic and Institute in Québec, Canada. The subject population consisted of 25 patients diagnosed with MCI meeting Petersen criteria and 25 healthy subjects serving as the normal control (NC) group. Three MoCA test versions were administered in the French language in random order within one session. Scores obtained in all three versions in MCI and NC groups were assessed for reliability and consistency from one version to the next. Results: On average, scores obtained in each subject group (MCI and NC) fell within their corresponding diagnostic ranges (score above 26 points for NC patients versus scores below 26 points for MCI patients). Difference in scores observed between the original French MoCA version and the two alternate versions in each subject cohort were minimal and not considered clinically significant. Conclusions: All three test versions of the French MoCA are considered equivalent in diagnostic reliability and consistency and contribute to decreasing the potential learning effect when patients are required to repeat the test frequently.
Classical neurosurgical teaching suggests that corticosteroid administration reduces the diagnostic yield of stereotactic brain biopsy for primary central nervous system lymphoma (PCNSL). In a single-center series spanning 6 years, we reviewed 155 consecutive biopsy patients, 135 treated with prebiopsy corticosteroids. PCNSL was correctly diagnosed on initial biopsy in 15 of 16 steroid-treated patients; in the single nondiagnostic specimen, polymerase chain reaction reanalysis by an outside institution showed evidence of lymphoproliferative disease consistent with PCNSL. Our data challenge the notion that it is necessary to withhold corticosteroid therapy for cerebral edema in patients awaiting stereotactic biopsy for suspected PCNSL.
Metronidazole (Flagyl®) is an antimicrobial agent commonly used in clinical practice. Although it is generally well tolerated with minimal side effects, there are a host of still under-recognized neurologic complications of metronidazole treatment. The following review is aimed at summarizing current literature pertaining to metronidazole-induced neurotoxicity including clinical syndromes, neuroradiological findings, prognosis and proposed pathophysiology. Recognition of the neurotoxic effects of metronidazole is critical as prompt discontinuation is generally associated with full clinical recovery and radiological resolution.
Background: Understanding the epidemiology of traumatic brain injury (TBI) is essential to shape public health policy, implement prevention strategies, and justify allocation of resources toward research, education, and rehabilitation in TBI. There is not, to our knowledge, a systematic review of population-based studies addressing the epidemiology of TBI that includes all subtypes. We performed a comprehensive systematic review and meta-analysis of the worldwide incidence of TBI. Methods: A search was conducted on May 23, 2014, in Medline and EMBASE according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Abstracts were screened independently and in duplicate to identify original research. Study quality and ascertainment bias were assessed in duplicate using a previously published tool. Demographic data and incidence estimates from each study were recorded, along with stratification by age, gender, year of data collection, and severity. Results: The search strategy yielded 4944 citations. Two hundred and sixteen articles met criteria for full-text review; 144 were excluded. Hand searching resulted in ten additional articles. Eighty-two studies met all eligibility criteria. The pooled annual incidence proportion for all ages was 295 per 100,000 (95% confidence interval: 274-317). The pooled incidence rate for all ages was 349 (95% confidence interval: 96.2-1266) per 100,000 person-years. Incidence proportion and incidence rate were examined to see if associated with age, sex, country, or severity. Conclusions: We conclude that most TBIs are mild and most TBIs occur in males among the adult population. The incidence of TBI varies widely by ages and between countries. Despite being an important medical, economic, and social problem, the global epidemiology of TBI is still not well-characterized in the current literature. Understanding the incidence of TBI, particularly mild TBI, remains challenging because of nonstandardized reporting among neuroepidemiological studies.
Background: Hereditary hemochromatosis (HH) is a genetic disorder causing pathological iron deposition and functional impairment of various organs, predominantly the liver. We assessed patients with HH for the presence of movement disorders. Methods: We reviewed the charts of 616 patients with HH who attended hemochromatosis clinic at London Health Sciences Centre, London, ON, Canada, from 1988 to 2015. Results: We found three HH patients with movement disorders, without any other major systemic manifestation. One had parkinsonism, another had chorea, and the third had tremor. All three patients had evidence of iron deposition in the brain, affecting the basal ganglia in the first two, and the dentate nucleus, red nucleus, and substantia nigra in the third patient. In addition to the C282Y homozygous mutation in the HFE gene, two of our patients had non-HFE gene mutations. Conclusion: HH should be considered in the differential diagnosis of movement disorders with pathological brain iron deposition. We report for the first time chorea in a patient with HH. Non-HFE gene mutations may predispose HH patients to iron deposition in the brain.