Reviews & Analysis

Multiple sclerosis (MS) is a complex disease with a high degree of clinical and neuropathological variability between patients. In this Viewpoint, Aksel Siva argues that such a heterogeneous disease demands a heterogeneous approach to treatment and questions the practice of initiating long-term immunotherapy before the MS diagnosis has become definite.

This article describes the case of a female patient who presented with transient right-sided weakness, and went on to develop further transient neurological signs and symptoms. A diagnosis of amyloid-β-related angiitis was made at autopsy following a sudden, fatal intracerebral hemorrhage. The authors highlight the importance of considering this diagnosis in patients with difficult-to-localize transient neurological symptoms.

Neuromyelitis optica (NMO) is a rare neuroinflammatory disorder that predominantly affects the optic nerves and spinal cord. NMO was originally considered to be a subtype of multiple sclerosis, but the recent discovery of NMO-specific serum autoantibodies has caused it to be reclassified as a distinct disease. In this article, Jariuset al. review clinical, serological and pathological findings in NMO, and discuss the evidence supporting an antibody-mediated mechanism in its pathogenesis.

This Case Study describes a 63-year-old woman with a history of metastatic breast cancer who presented with rapidly progressing myelopathic symptoms and an elevated titer for the neuromyelitis optic antibody. The appearance of myelopathy correlated with recurrence of the patient's breast cancer on two separate occasions, and the authors suggest this case represents a possible paraneoplastic syndrome associated with the neuromyelitis antibody.

Mandatory generic substitution of antiepileptic drugs is an increasingly common practice that has many physicians and patients concerned because of the potential for breakthrough seizures and adverse effects. Do the same concerns apply to the treatment of newly diagnosed epilepsy? Peter Wolf investigates.

Although there have been substantial innovations in antiepileptic drug therapy over the past 15 years, the proportion of patients with medically refractory epilepsy has remained largely unchanged, highlighting the need for new therapeutic strategies. In this article, Stacey and Litt review recent progress in the development of implantable devices designed to detect, predict and extinguish seizures, and consider the challenges that lie ahead, including improvements in seizure prediction and personalized control.

Over the past century, the pathophysiology of ischemia in the borderzones between the large cerebral arteries has been the topic of considerable debate. Two seemingly mutually exclusive mechanisms—hemodynamic failure and microembolism—have been proposed to explain this phenomenon. As Förster et al. discuss in this article, a new model of borderzone infarction, incorporating both hypoperfusion and microembolism, is now emerging.

In this Case Study, a 66-year-old man presented with a clinical syndrome consistent with frontal variant frontotemporal dementia, but neuropathological evidence established a diagnosis of frontal variant Alzheimer's disease. The authors provide detailed, longitudinal clinical data describing the course of this rare but increasingly recognized variant of Alzheimer's disease.

Duchenne muscular dystrophy is an X-linked recessively inherited disorder of skeletal and cardiac muscle that is caused by mutations in the dystrophin gene. In this article, Lim and Rando describe new mutation-specific therapeutic strategies that use nonviral agents to target nonsense point mutations or frameshift deletions at the dystrophin locus, with the ultimate aim of developing 'personalized' gene therapy for Duchenne muscular dystrophy.

Autism spectrum disorders (ASDs) are characterized by qualitative impairments in the development of social and communication skills, often accompanied by stereotyped and restricted patterns of interests and behaviors. ASDs are usually diagnosed between the ages of 3 and 6 years, but, as Rebecca Landa discusses in this Review, there is increasing evidence that a diagnosis can be made in the second year of life in some children. She argues that early diagnosis and intervention are likely to lead to improved outcomes in children with ASDs.

Inflammatory responses to CNS infections can cause severe disability or even death, and pharmacological treatments that dampen inflammation might, therefore, be beneficial adjunctive treatments in such cases. In this article, Fitch and van de Beek review the available evidence that steroids, administered in conjunction with appropriate antimicrobial therapy, can improve outcomes in patients with bacterial meningitis, tuberculous meningitis or herpes simplex virus encephalitis.

This Case Study describes in detail a case of Lafora disease, from its earliest stages through the clinical progression, including detailed neurophysiological studies, diagnostic biopsy and autopsy.

To devise therapeutic strategies for the rehabilitation of patients with hemiparetic stroke, it is important to understand the mechanisms that underlie the neuroplasticity induced by skills training and exercise programs. In this Review, Dobkin considers how basic neurobiological mechanisms might be exploited to enhance motor recovery after stroke, and to enable patients to participate more fully in activities of daily life.

Oxidative stress seems to be a common factor in the pathogenesis of inherited ataxias, prompting attempts to treat these conditions with antioxidants. In this Review, Massimo Pandolfo discusses the rationale for antioxidant treatment in inherited ataxias, and describes the results of the clinical trials conducted to date, focusing particularly on the use of coenzyme Q analogs to treat Friedreich ataxia.

The conceptualization of attention-deficit hyperactivity disorder (ADHD) has been the subject of some controversy. In this article, two US-based academic child psychiatrists discuss the prevailing approach to diagnosis and treatment of ADHD in the USA and suggest potential reasons for the variability in prevalence estimates between the USA and Europe.

Despite much research, it has been difficult to gain professional agreement on what attention-deficit hyperactivity disorder (ADHD) is and how it should be treated. In this Viewpoint, Peter Hill—who has been running treatment and consultative services for ADHD at a national level in the UK for over 20 years—offers his observations on how the disorder is handled in the UK.

Axon degeneration is a major contributor to disability in multiple sclerosis, and sodium channels have been shown to have a crucial role in this process. In this article, Waxman reviews the development of the concept of sodium channel blockers as neuroprotectants in multiple sclerosis, and discusses recent attempts to translate this approach from the laboratory to the clinic.

Subthalamic nucleus stimulation in individuals with Parkinson's disease can result in spectacular motor improvement, but many patients find it difficult to cope with this sudden change in their condition. In this Viewpoint, Schüpbach and Agid look at possible explanations for difficulties in social adjustment after surgery and suggest strategies to facilitate adaptation to a new lifestyle.

This Case Study describes a 78-year-old man with a pre-existing parkinsonian syndrome who experienced an adverse drug reaction following administration of an antipsychotic in combination with a cholinesterase inhibitor. The patient was diagnosed with a variant of neuroleptic malignant syndrome.

This Case Study describes a 80-year-old patient with lower-body parkinsonism who was diagnosed with vascular parkinsonism on the basis of clinical and neuroimaging findings, but whose gait and, to a lesser extent, cognitive impairments improved following external lumbar drainage. Postmortem neuropathology confirmed a diagnosis of normal pressure hydrocephalus.