Future Neurology

Mutations in the Fragile X Mental Retardation 1 ( FMR1 ) gene create a spectrum of developmental disorders in children in addition to neurodegenerative problems in older populations. Two types of mutations are recognized in the FMR1 gene. The full mutation (>200 CGG repeats) in the FMR1 gene leads to Fragile X Syndrome which is the most common inherited cause of intellectual disability and autism, while the premutation (55 to 200 CGG repeats) identified among carriers leads to a range of problems linked to elevated levels of the FMR1 mRNA leading to mRNA toxicity and occasionally mildly deficient FMRP levels...

Infantile-onset spinal muscular atrophy (SMA) is a prototypical disease in which to investigate selective neurodegenerative phenotypes. Caused by low levels of the ubiquitously expressed Survival Motor Neuron (SMN) protein, the disease mainly targets the spinal motor neurons. This selective phenotype remains largely unexplained, but has not hindered the development of SMN repletion as a means to a treatment. Here we chronicle recent advances in the area of SMA biology. We provide a brief background to the disease, highlight major advances that have shaped our current understanding of SMA, trace efforts to treat the condition, discuss the outcome of two promising new therapies and conclude by considering contemporary as well as new challenges stemming from recent successes within the field...

Huntington disease (HD) is an autosomal dominantly inherited neurodegenerative disease that affects motor, cognitive and psychiatric functions, and ultimately leads to death. The pathology of the disease is based on an expansion of CAG repeats in exon 1 of the huntingtin gene on chromosome 4, which produces a mutant huntingtin protein (mHtt). This protein is involved in neurotoxicity and brain atrophy, and can form β-sheets and abnormal mHtt aggregates. Currently, there are no approved effective treatments for HD, although tetrabenazine (Xenazine™) and deutetrabenazine (AUSTEDO™) have been approved for treatment of the motor symptom chorea in HD...

Nearly a third of patients with epilepsy have seizures refractory to current medical therapies. In the search for novel drug targets, the mTOR pathway has emerged as key in the regulation of neuronal function, growth and survival, and other cellular processes related to epileptogenesis. Hyperactivation of the mTOR pathway has been implicated in tuberous sclerosis complex and other 'mTORopathies', clinical syndromes associated with cortical developmental malformations and drug-resistant epilepsy. Recently published clinical trials of mTOR inhibitors in tuberous sclerosis complex have shown that these drugs are effective at decreasing seizure frequency...

Appearing in 40% of the cases of autism spectrum disorder (ASD), comorbid anxiety presents unique challenges for practitioners by amplifying problem behaviors such as social skills deficits, resistance to change and repetitive behaviors. Furthermore, comorbid ASD/anxiety strains familial relationships and increases parental stress. Research indicates that the neurobiological interactions between anxiety and ASD require comprehensive assessment approaches, modified cognitive behavioral therapy and carefully managed pharmacological interventions...

Brain activity levels are tightly regulated to minimize imbalances in activity state. Deviations from the normal range of activity are deleterious and often associated with neurological disorders. To maintain optimal levels of activity, regulatory mechanisms termed homeostatic synaptic plasticity establish desired 'set points' for neural activity, monitor the network for deviations from the set point and initiate compensatory responses to return activity to the appropriate level that permits physiological function [1,2]...

Streptococcus pyogenes infections have been associated with two autoimmune diseases of the CNS: Sydenham's chorea (SC) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus infections (PANDAS). Despite the high frequency of pharyngeal streptococcus infections among children, only a small fraction develops SC or PANDAS. This suggests that several factors in combination are necessary to trigger autoimmune complications: specific S. pyogenes strains that induce a strong immune response toward the host nervous system; genetic susceptibility that predispose children toward an autoimmune response involving movement or tic symptoms; and multiple infections of the throat or tonsils that lead to a robust Th 17 cellular and humoral immune response when untreated...

AIM: Report a case of cortical subarachnoid hemorrhage (cSAH) and discuss its management. PATIENT & METHODS: A 66-year-old woman presents with acute onset left arm numbness and weakness. Initial head CT shows small hyperdensity in sulci typical for cSAH. Extensive workup with MRI, lumbar puncture and blood tests is performed. No signs of infection, vascular malformations, thrombosis or cancer are found. At outpatient follow-up, she is diagnosed with cSAH secondary to amyloid angiopathy...

Valproic acid and lithium are widely used to treat bipolar disorder, a severe illness characterized by cycles of mania and depression. However, their efficacy is limited, and treatment is often accompanied by serious side effects. The therapeutic mechanisms of these drugs are not understood, hampering the development of more effective treatments. Among the plethora of biochemical effects of the drugs, those that are common to both may be more related to therapeutic efficacy. Two common outcomes include inositol depletion and GSK3 inhibition, which have been proposed to explain the efficacy of both valproic acid and lithium...

Late-onset Alzheimer's disease (AD), a highly prevalent neurodegenerative disorder characterized by progressive deterioration in cognition, function and behavior terminating in incapacity and death, is a clinically and pathologically heterogeneous disease with a substantial heritable component. During the past 5 years, the technological developments in next-generation high-throughput genome technologies have led to the identification of more than 20 novel susceptibility loci for AD, and have implicated specific pathways in the disease, in particular intracellular trafficking/endocytosis, inflammation and immune response and lipid metabolism...

No abstract text is available yet for this article.

Child-bearing years are often the most precarious management period in the life of a woman with epilepsy. This article reviews the results of many different studies with findings that enable the healthcare team to make confident decisions and recommendations during these critical periods. Preconceptional planning, effective contraception and folic acid supplementation are important fundamentals in preparation for pregnancy. There is growing evidence to avoid valproic acid use during the child-bearing years...

No abstract text is available yet for this article.

The hippocampo-prefrontal (H-PFC) pathway has been linked to cognitive and emotional disturbances in several psychiatric disorders including schizophrenia. Preclinical evidence from the NMDA receptor antagonism rodent model of schizophrenia shows severe pathology selective to the H-PFC pathway. It is speculated that there is an increased excitatory drive from the hippocampus to the prefrontal cortex due to dysfunctions in the H-PFC plasticity, which may serve as the basis for the behavioral consequences observed in this rodent model...

MRI and magnetic resonance spectroscopy (MRS) along with computed tomography and PET are the most common imaging modalities used in the clinics to detect structural abnormalities and pathological conditions in the brain. MRI generates superb image resolution/contrast without radiation exposure that is associated with computed tomography and PET; MRS and spectroscopic imaging technologies allow us to measure changes in brain biochemistry. Increasingly, neurobiologists and MRI scientists are collaborating to solve neuroscience problems across sub-cellular through anatomical levels...

The immune system generates antibodies and antigen-specific T-cells as basic elements of the immune networks that differentiate self from non-self in a finely tuned manner. The antigen-specific nature of immune responses ensures that normal immune activation contains non-self when tolerating self. Here we review the B-1 subset of lymphocytes which produce self-reactive antibodies. By analyzing the IgM class of natural antibodies that recognize antigens from the nervous system, we emphasize that natural antibodies are biomarkers of how the immune system monitors the host...

Advances in neuroimaging have helped illuminate our understanding of how the brain works in the presence of chronic pain, which often persists with unknown etiology or after the painful stimulus has been removed and any wounds have healed. Neuroimaging has enabled us to make great progress in identifying many of the neural mechanisms that contribute to chronic pain, and to pinpoint the specific regions of the brain that are activated in the presence of chronic pain. It has provided us with a new perception of the nature of chronic pain in general, leading researchers to move toward a whole-brain approach to the study and treatment of chronic pain, and to develop novel technologies and analysis techniques, with real potential for developing new diagnostics and more effective therapies...

A young women developed unilateral facial neuropathy 2 weeks after a motor vehicle collision involving fractures of the skull and mandible. MRI showed contrast enhancement of the facial nerve. We review the literature describing facial neuropathy after trauma and facial nerve enhancement patterns with different causes of facial neuropathy.

Translation from basic science bench research in ischemic stroke to bedside treatment of patients suffering ischemic stroke remains a difficult challenge. Despite literally hundreds of compounds and interventions that provide benefit in experimental models of cerebral ischemia, efficacy in humans remains to be demonstrated. The reasons for failure to translate the extensive positive basic science findings to successful clinical trials have been the focus of discussion for years. Some attribute the failure to flaws in clinical trial design, others question the predictive value of current animal models and some question the quality of preclinical data...

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