Handbook of clinical neurology
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Tinnitus is a common disorder and traditional treatment approaches such as medication, active or passive sound enhancement, and cognitive behavioral therapy have limited efficacy. Thus, there is an urgent need for more effective treatment approaches. Functional imaging studies in patients with tinnitus have revealed alterations in neuronal activity of central auditory pathways, probably resulting as a consequence of sensory deafferentation. ⋯ Transcranial direct current stimulation (tDCS) has also shown potential for the treatment of tinnitus. Both auditory and frontal tDCS have shown tinnitus reduction in a subgroup of patients. In spite of the promising results of the different brain stimulation approaches, further research is needed before these techniques can be recommended for routine clinical use.
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Epilepsies associated with inborn errors of metabolism (IEM) represent a major challenge. Seizures rarely dominate the clinical presentation, which is more frequently associated with other neurological symptoms, such as hypotonia and/or cognitive disturbances. Although epilepsy in IEM can be classified in various ways according to pathogenesis, age of onset, or electroclinical presentation, the most pragmatic approach is determined by whether they are accessible to specific treatment or not. ⋯ Folinic acid-dependent seizures are allelic with pyridoxine dependency. Incompletely treatable IEMs include pyridoxal phosphate, serine, and creatine deficiencies. The main IEMs that present with epilepsy but offer no specific treatment are nonketotic hyperglycinemia, mitochondrial disorders, sulfite oxidase deficiency, ceroid-lipofuscinosis, Menkes disease, and peroxisomal disorders.
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A variety of noninvasive brain stimulation techniques have been used to study neuronal plasticity. Mostly, noninvasive techniques have been employed, and the bulk of studies have focused on the motor system, because its physiology is more readily accessible and physiological properties can be studied with greater detail than in other systems. ⋯ Several of the phenomena induced by noninvasive brain stimulation have been mapped on to cellular physiological mechanisms such as synaptic long-term potentiation or long-term depression. Although some parallelisms are intriguing, this approach has also its limitations, and more direct verification of physiological phenomena by animal studies is needed.
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One of the most exciting areas in epilepsy has been the explosion in our understanding of the genetics of the epilepsies over the last decade. Built on a long history of careful clinical genetic studies of the epilepsies, the relatively recent discovery of epilepsy genes has enabled insights into pathways causing seizure disorders. A variety of mutational mechanisms can cause epilepsy resulting from different, and sometimes surprising, molecular processes such as copy number variation within the genome. ⋯ The architecture of the common genetic epilepsies following complex inheritance, where multiple genes are involved, is also beginning to be unraveled. The clinical approach to understanding the genetics of the epilepsies has matured and requires a detailed family history of seizures together with delineation of the child's epilepsy syndrome. Recognition of specific genetic epilepsy syndromes enables optimal treatment and prognostic and genetic counseling.
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Fabry disease results from deficient activity of the enzyme α-galactosidase A and progressive lysosomal deposition of globotriaosylceramide (GL-3) in cells throughout the body. The main neurological presentations of Fabry disease patients are painful neuropathy, hypohidrosis, and stroke. Fabry neuropathy is characterized as a length-dependent peripheral neuropathy affecting mainly the small myelinated (Aδ) fibers and unmyelinated (C) fibers. ⋯ Early initiation of ERT before irreversible organ failure is extremely important, and alternative therapeutic approaches are currently being explored. Heterozygotes suffer from peripheral neuropathy at a higher rate than previously shown, significant multisystemic disease, and severely decreased quality of life. As well as being carriers, heterozygotes also display symptoms of Fabry disease, and should be carefully monitored and given adequate therapy.