Lennox-Gastaut syndrome (LGS) is a severe epileptic encephalopathy. Few current treatment options are effective in improving seizure control. This paper reviews the available treatments of LGS and discusses a new option in Canada, rufinamide. It is a wide spectrum anticonvulsant, approved in a number of countries for the treatment of LGS. In a randomized controlled trial in the LGS population, adjunctive rufinamide therapy has been shown to offer significantly greater reduction in total seizure frequency and tonic-atonic seizure frequency in comparison to placebo. Efficacy has been assessed over three years and appears to be sustained. Most adverse events were cognitive (e.g. somnolence) or gastrointestinal in nature and in many cases transient or mild. Based on the efficacy and safety data on rufinamide obtained to date, this medication will provide additional benefits to patients with LGS in Canada and is an important consideration for our patients in the adjunctive treatment setting.

Neuropathic pain often fails to respond to conventional pain management procedures. here we review the aetiology of neuropathic pain as would result from peripheral neuropathy or injury. We show that inflammatory mediators released from damaged nerves and tissue are responsible for triggering ectopic activity in primary afferents and that this, in turn, provokes increased spinal cord activity and the development of ‘central sensitization’. Although evidence is mounting to support the role of interleukin-1β, prostaglandins and other cytokines in the onset of neuropathic pain, the clinical efficacy of drugs which antagonize or prevent the actions of these mediators is yet to be determined. basic science findings do, however, support the use of pre-emptive analgesia during procedures which involve nerve manipulation and the use of anti-inflammatory steroids as soon as possible following traumatic nerve injury.

Status epilepticus is among the most dramatic of clinical presentations encountered by emergency room physicians, neurologists, neurosurgeons and intensivists. While progress in its management has been aided significantly with an increasing number of effective treatment options, improved diagnostic methods and more effective monitoring, poor outcomes and diagnostic failures are still frequently encountered. Refractory cases still carry significant morbidity and mortality rates, including poor cognitive outcomes. This review discusses basic pathophysiology and management of status epilepticus, neuroimaging findings, the role of continuous electroencephalogram monitoring and nonconvulsive status epilepticusas well as recent developments in treatment options for refractory cases.

Brain biopsy plays a crucial role in the exploration of suspect white matter lesions in the differential diagnosis of primary central nervous system lymphoma (PCNSL) and inflammatory demyelination. We present the case of a previously healthy, immunocompetent woman, aged fifty-nine, who developed a histologically confirmed demyelinating white matter lesion months prior to the manifestation of a PCNSL. Similar cases of “sentinel lesions” preceding a PCNSL have been reported. In a literature review, we compared the diagnostic features that may be useful to differentiate a PCNSL from inflammatory demyelinating disease in older age. We conclude that the occurrence of large, contrast-enhancing cerebral lesions in older patients with a relapsing-remitting disease course and steroid-resistant vision disorders should lead to the consideration of a PCNSL.

Alzheimer's disease (AD) is poised to become the most serious healthcare issue of our generation. The leading theory of AD pathophysiology is the Amyloid Cascade Hypothesis, and clinical trials are now proceeding based on this hypothesis. Here, we review the original evidence for the Amyloid Hypothesis, which was originally focused on the extracellular deposition of beta amyloid peptides (Aβ) in large fibrillar aggregates, as well as how this theory has been extended in recent years to focus on highly toxic small soluble amyloid oligomers. We will also examine emerging evidence that Aβ may actually begin to accumulate intracellularly in lysosomes, and the role for intracellular Aβ and lysosomal dysfunction may play in AD pathophysiology. Finally, we will review the clinical implications of these findings.

This mini-review will summarize some of the major contributions of Neuropathology to understanding the structural basis of several forms of intractable epilepsy. Because of space limitations, only selected morphologically defined brain abnormalities will be considered and illustrated. By definition, the types of specimen encountered by Neuropathologists are those resected to treat intractable seizure disorders. One can therefore infer that the 'lesions' encountered in some way caused or at least contributed to the epilepsy, though the leap from observed neuropathologic abnormalities to 'seizuregenesis' is not always straightforward—indeed often is very tortuous and obscure. Nevertheless, a Neuropathologist working with a team of neurologists, neurosurgeons, electrophysiologists, neuropsychologists, and others, can contribute to a richer understanding of why seizures are triggered within human brain tissue, and therefore how they may be more effectively treated.

With the growing interdependence between medicine and technology, the prospect of connecting machines to the human brain is rapidly being realized. The field of neuroprosthetics is transitioning from the proof of concept stage to the development of advanced clinical treatments. In one area of brain-machine interfaces (BMIs) related to the motor system, also termed ‘motor neuroprosthetics’, research successes with implanted microelectrodes in animals have demonstrated immense potential for restoring motor deficits. Early human trials have also begun, with some success but also highlighting several technical challenges. Here we review the concepts and anatomy underlying motor BMI designs, review their early use in clinical applications, and offer a framework to evaluate these technologies in order to predict their eventual clinical utility. Ultimately, we hope to help neuroscience clinicians understand and participate in this burgeoning field.

Early-onset familial Alzheimer's disease (EOFAD) is a condition characterized by early onset dementia (age at onset < 65 years) and a positive family history for dementia. To date, 230 mutations in presenilin (PS1, PS2) and amyloid precursor protein (APP) genes have been identified in EOFAD. The mutations within these three genes (PS1/PS2/APP) affect a common pathogenic pathway in APP synthesis and proteolysis, which lead to excessive production of amyloid β. Compared with sporadic Alzheimer's disease (AD), EOFAD has some distinctive features including early age at onset, positive familial history, a variety of non-cognitive neurological symptoms and signs, and a more aggressive course. There is marked phenotypic heterogeneity among different mutations of EOFAD. Studies in presymptomatic mutation carriers reveal biomarkers abnormalities. EOFAD diagnosis is based on clinical and family history, neurological symptoms and examination, biomarker features, as well as genotyping in some cases. New therapeutic agents targeting amyloid formation may benefit EOFAD individuals.

Alzheimer's disease (AD), considered the commonest neurodegenerative cause of dementia, is associated with hallmark pathologies including extracellular amyloid-β protein (Aβ) deposition in extracellular senile plaques and vessels, and intraneuronal tau deposition as neurofibrillary tangles. Although AD is usually categorized as neurodegeneration distinct from cerebrovascular disease (CVD), studies have shown strong links between AD and CVD. There is evidence that vascular risk factors and CVD may accelerate Aβ 40-42 production/ aggregation/deposition and contribute to the pathology and symptomatology of AD. Aβ deposited along vessels also causes cerebral amyloid angiopathy. Amyloid imaging allows in vivo detection of AD pathology, opening the way for prevention and early treatment, if disease-modifying therapies in the pipeline show safety and efficacy. In this review, we review the role of vascular factors and Aβ, underlining that vascular risk factor management may be important for AD prevention and treatment.

Cerebral palsy is traditionally known as a major cause of chronic disability in childhood. With advances in neonatal care and improved survival, the majority of adolescents with cerebral palsy require ongoing services into adulthood. This paper highlights some of the challenges in their transition from pediatric to adult healthcare and proposes key elements to ensure a smooth transition process.

In Part I, neuroscience collaborators with the Nazis were discussed, and in Part II, neuroscience resistors were discussed. In Part III, we discuss the tragedy regarding european neuroscientists who became victims of the Nazi onslaught on “Non-Aryan” doctors. Some of these unfortunate neuroscientists survived Nazi concentration camps, but most were murdered. We discuss the circumstances and environment which stripped these neuroscientists of their profession, then of their personal rights and freedom, and then of their lives. We include a background analysis of anti-Semitism and Nazism in their various countries, then discuss in depth seven exemplary neuroscientist Holocaust victims; including germans Ludwig Pick, Arthur Simons, and Raphael Weichbrodt, Austrians Alexander Spitzer and Viktor Frankl, and Poles Lucja Frey and Wladyslaw Sterling. By recognizing and remembering these victims of neuroscience, we pay homage and do not allow humanity to forget, lest this dark period in history ever repeat itself.

Epilepsy surgery is a highly effective and durable treatment for specific types of drug resistant epilepsy such as temporal lobe epilepsy. assessment of outcomes is essential in epilepsy surgery, which is an irreversible intervention for a chronic condition. Excellent short-term results of resective epilepsy surgery have been established. In the last years more information regarding long term outcomes have been published. This article reviews the best available evidence about the best measures to assess outcomes and the most important evidence. The outcomes reviewed in this article are the following: seizure outcome, social and psychiatric outcomes, complications and mortality.

Dynamic radiosurgery was first developed in Montreal and was subsequently adopted at the Toronto-Bayview Regional Cancer Centre in 1988. At that time radiosurgery was in its infancy in Canada. The opportunity of offering highly conformal radiation treatments for intracranial targets presented numerous technical challenges notably in the area of quality assurance. This review chronicles the development of radiosurgery at the Toronto-Bayview Regional Cancer Centre and summarises the successes and failures of the program over the following two decades.