Reviews & Analysis

Patients with multiple sclerosis (MS) frequently experience depression, which profoundly reduces quality of life, and increases disease mortality. In this Review, Feinstein and colleagues present multiple approaches to the diagnosis and quanitfication of mood disorders, and critically evaluate the various treatment options for MS-related depression.The authors also discuss the extent to which depression can be teased apart from the neurological, immunological and psychosocial sequelae of MS.

More than 80% of patients with the demyelinating disorder neuromyelitis optica (NMO) experience pain from this condition, which severely affects their quality of life. NMO-associated pain is largely refractory to contemporary pain therapy, suggesting that the mechanisms underlying pain in NMO differ from those underlying other causes of pain. In this article, Bradl and colleagues explore the mechanisms underlying pain in patients with NMO, and attempt to identify molecular and cellular targets for therapy.

Several distinct autoimmune neuropathies can be referred to collectively as Guillain–Barré syndrome (GBS). Wakerley and colleagues argue that confusing terminology hinders diagnosis, and they present a revised classification of 'classic' GBS, Miller Fisher syndrome and related conditions. This new approach to diagnosis might facilitate work-up, thereby helping to identify the correct treatment as quickly as possible.

Autism is arguably the quintessential neurodevelopmental disorder. However, despite an explosion of research over the past decade, we know relatively little about the development of autism itself. Recent longitudinal research has provided important new insights—and has raised new questions—concerning the complexities of the disorder.

Guillain–Barré syndrome (GBS) is a postinfectious disease characterized by rapidly progressive, symmetrical weakness of the extremities, and can lead to life-threatening complications such as respiratory insufficiency and autonomic dysfunction. Here, van den Berg et al. describe the immune pathogenesis and clinical characteristics of GBS and its subtypes, and highlight the importance of careful diagnostic assessment of patients and the possible additional diagnostic value of cerebrospinal fluid examinations and nerve conduction tests. The authors review treatment options and prognosis, including novel predictive models, for patients with GBS.

Dopaminergic brain imaging might aid early diagnosis of Parkinson disease (PD), but some patients with mild symptoms show no evidence of dopaminergic dysfunction at baseline, and apparently do not progress. Although some of these patients may have been misdiagnosed, others continue to fulfil PD diagnostic criteria despite normal follow-up brain scans.

Discovery of the endogenous cannabinoid signalling system unleashed substantial new research into several neurological conditions. A recent systematic review suggests that medical marijuana can improve a number of symptoms—particularly spasticity—in multiple sclerosis, but cannabinoids can have adverse psychological effects and their comparative effectiveness is unknown.

Optic neuritis is an inflammatory optic neuropathy that is frequently—but not always—associated with multiple sclerosis (MS). Despite recent developments in laboratory, imaging and electrophysiological techniques, no consensus guidelines have yet been formulated for the diagnostic work-up in patients presenting with optic neuritis. In this Review, Petzold and colleagues contribute to the development of such a consensus by proposing an investigation protocol for optic neuritis.

Brain imaging and histopathological studies have suggested that iron plays a crucial part in the pathophysiology of multiple sclerosis (MS). In this Review, Yong and colleagues discuss the growing evidence of widespread dysregulation of iron metabolism associated with MS, from focal iron deposits around grey matter lesions to iron deficits in white matter that might interfere with remyelination and other cellular repair processes. The authors then outline several potential mechanisms for treating iron dysregulation that balance the trophic and toxic properties of this molecule.

Correct diagnosis of chronic neuropathies is paramount, because acquired neuropathies are frequently immune-mediated and, thus, amenable to treatment. Distinction between different types of neuropathies, however, is not trivial. In this Review, Norman Latov discusses clinical presentation, differential diagnosis and treatment of chronic acquired demyelinating neuropathies, and suggests a diagnostic pathway for clinical practice.

Differential diagnosis in the vegetative and minimally conscious states is notoriously difficult. A new report compares the diagnostic accuracy of two neuroimaging methods, using bedside behavioural assessment as a reference. The results highlight the many theoretical and methodological challenges in studying this patient group.

Sex differences are increasingly recognized in many areas of medicine, and stroke is no exception. Women tend to be more adversely affected by stroke than are men and, as a new study illustrates, this discrepancy cannot be attributed solely to sex-related differences in acute stroke care.

The DNA repair proteinO⁶-methylguanine-DNA methyltransferase (MGMT) might interfere with alkylating agent chemotherapy in patients with glioma or glioblastoma. In this Review, Wick and colleagues discuss how epigenetic silencing of the MGMT gene via promotor methylation is associated with improved response to chemotherapy, and with improved survival, in patients with glioblastoma and other gliomas. The authors also highlight the usefulness of MGMTpromotor methylation as a biomarker for both clinical practice and the design of treatment trials.

Pruritus is a very common condition, with almost one-third of the global population experiencing itch in a given week. Its origin is not always in the skin: damage to neurons or glia can induce neuropathic pruritus, which is often associated with neuropathic pain. Neuropathic pruritus is often difficult to treat and—if chronic—can severely impair quality of life. Here, Laurent Misery and colleagues review the role of the nervous system and neuropathic syndromes in pruritus, summarize the currently available therapeutic options, and propose therapeutic strategies for managing neuropathic pruritus.

Aggressive, refractory multiple sclerosis warrants unconventional therapy. A retrospective multicentre study assessed the effects of ablating the immune system, then reconstituting it using bone marrow derived stem cells. Though this particular regimen improved disability in some patients, others continued to relapse, perhaps indicating the treatment did not go far enough.

Cataplexy is the pathognomonic symptom of narcolepsy, a condition that is caused by depletion of orexin neurons. Cataplectic attacks are characterized by sudden involuntary muscle weakness or paralysis, often triggered by strong emotions. In this article, Dauvilliers et al. review the latest understanding of potential mechanisms underlying narcolepsy and cataplexy, the utility of experimental models, and the need for early diagnosis and therapy.

Medication overuse headache (MOH) is a widespread problem, and no global consensus has yet been reached regarding its management. In an attempt to address this issue, six headache centres have collaborated to evaluate a detoxification protocol in a large cohort of patients with MOH from Europe and South America.

Preimplantation genetic diagnosis (PGD) facilitates conception of a healthy child by couples at risk of having offspring with an inherited debilitating or fatal neurological disorder. PGD has been carried out for various conditions, including spinal muscular atrophy, Huntington disease, fragile X syndrome, and chromosomal and mitochondrial disorders. This article aims to assist neurologists in counselling and treatment of individuals who wish to explore the option of PGD, and advocates the formulation of guidelines for the responsible integration of PGD into preventative neurology.

Central and peripheral neurological disorders can present with autonomic failure or hyperactivity, which can affect the sympathetic, parasympathetic and/or enteric nervous systems. This Review outlines the clinical approach to patients with generalized autonomic failure, focusing predominantly on classification and diagnosis, but also touching briefly on treatment and management. A systematic approach to diagnosis is essential to enable detection of treatable, potentially disabling or life-threatening conditions.

A recent multicentre study has assessed the risk of relapse in patients with multiple sclerosis who switched from natalizumab to fingolimod treatment. Despite such efforts, no effective exit strategy from natalizumab treatment has yet been demonstrated for these patients.