Showing papers in "Current Opinion in Neurology in 2002"
TL;DR: It is concluded that much progression has been made in magnetic resonance techniques so that the clinico‐radiological dissociation has indeed proved to be a paradox, and corroborates with conventional wisdom that one should not rely on a single magnetic resonance measure, but take full advantage of the fact that magnetic resonance is able to provide multidimensional information.
Abstract: The use of magnetic resonance imaging as a surrogate outcome measure in clinical trials, or even as a prognosticator in the assessment of the natural evolution, assumes a close relationship between extent and rate of development of magnetic resonance imaging abnormalities with the clinical status and rate of development of disability. While it may seem obvious that patients who develop new lesions are worse off than those without new lesions, the association between clinical findings and radiological extent of involvement is generally poor. In this review, various confounders are discussed, including inappropriate clinical rating, lack of histopathological specificity (especially for axonal loss), neglect of spinal cord involvement, underestimation of damage to the normal appearing brain tissue (both white and gray matter), and masking effects of cortical adaptation. It is concluded that much progression has been made in magnetic resonance techniques so that the clinico-radiological dissociation has indeed proved to be a paradox. Thus, the relevance of normal appearing brain tissue damage, residual brain volume, spinal cord damage and cerebral plasticity had to be reiterated. The increased awareness of the subtle interplay between these dimensions should be kept in mind when magnetic resonance is used as a surrogate outcome measure. This corroborates with conventional wisdom that one should not rely on a single magnetic resonance measure, but take full advantage of the fact that magnetic resonance is able to provide multidimensional information.
640 citations
TL;DR: This work has investigated sound processing by the unconscious brain; such investigations may provide a ‘window’ into residual brain function and prognosis in disorders such as tinnitus.
Abstract: Central auditory processing is essential for the perception of speech, environmental sounds and music, and may be deranged in two ways. Lesions of the ascending auditory pathway or cortex can produce deficits. Abnormal activity of the central auditory system is becoming increasingly recognized in disorders such as tinnitus. Recent work has investigated sound processing by the unconscious brain; such investigations may provide a 'window' into residual brain function and prognosis.
316 citations
TL;DR: In this session, insights into the mechanisms of oligodendrocyte injury and the role of inflammatory substances in perinatal brain injury are discussed.
Abstract: Major advances in understanding the cellular mechanisms of brain injury have presented a host of potential targets for intervention. This is particularly true of hypoxic-ischemic injury, the most important form of perinatal brain injury. As the window for effective clinical intervention may be particularly narrow in the fetus and newborn because of the often-delayed and subtle presentation of the onset of the insult, recent focus has been on defining and countering the more delayed mechanisms of brain injury. Recent insights into the mechanisms of oligodendrocyte injury and the role of inflammatory substances in perinatal brain injury are also discussed.
302 citations
TL;DR: An increasing body of literature supports the hypothesis that acute inflammatory events are attenuated by therapeutic hypothermia and other anti‐inflammatory strategies, whereas immune neuroprotection and axonal regeneration can be achieved by transfer of activated T cells or by treatment with therapeutic vaccines.
Abstract: Both acute and chronic inflammatory processes have been shown to influence outcome in experimental models of spinal cord injury. Although early inflammatory responses may participate in secondary injury processes, more delayed inflammatory events may be reparative. Therapeutic strategies that target these events are currently based on experimental findings that have clarified the cellular and molecular processes involved in the inflammatory response to injury. An increasing body of literature supports the hypothesis that acute inflammatory events are attenuated by therapeutic hypothermia and other anti-inflammatory strategies, whereas immune neuroprotection and axonal regeneration can be achieved by transfer of activated T cells or by treatment with therapeutic vaccines. These data are summarized in the present review.
214 citations
TL;DR: There is now evidence to suggest that a peripheral infection, and its consequent systemic cytokine expression, may drive central nervous system cytokineexpression and perhaps exacerbate disease.
Abstract: The inflammatory response in prion diseases is dominated by microglial activation. Contrary to their profile in vitro none of the pro-inflammatory cytokines interleukin-1β, interleukin-6, or tumour necrosis factor-α are significantly upregulated in the ME7 model of prion disease. However, two major
179 citations
TL;DR: Improved understanding of neurotoxic mechanisms in the peripheral nervous system associated with chemotherapeutic and anti-HIV medications, coupled with early improved diagnosis, promises to help limit neurotoxicity associated with these medications.
Abstract: Purpose of reviewPeripheral neuropathy is a common neurotoxic effect of medications. When medications are used to treat life-threatening illnesses, balancing the toxic effects of peripheral neuropathy with the therapeutic benefits of the drug can be difficult. This article examines recent research i
167 citations
TL;DR: The notion of a preseizure state is catalyzing new clinical and basic science research, which has the potential to dramatically increase the understanding of epilepsy, and to generate exciting new therapies for patients.
Abstract: Beginning in the 1970s engineers designed systems to predict epileptic seizures based upon quantitative changes in the electroencephalogram, which they hypothesized began well in advance of clinical seizure onset. These efforts flourished in the 1990s, as independent laboratories demonstrated evidence of a 'preseizure period' up to 20 min prior to clinical symptoms in patients implanted with intracranial electrodes during evaluation for epilepsy surgery. Years later, clinical and laboratory experiments leave little doubt that a preseizure period exists in temporal lobe and perhaps other forms of epilepsy. Its existence, however, raises fundamental questions about what constitutes a seizure, what brain regions are involved in seizure generation, and whether discrete interictal, preictal, ictal and post-ictal physiologies exist, or blend together in a continuous process. Pressing milestones, necessary for clinical utility, are: (1) demonstrating prospective seizure prediction from prolonged human data sets, (2) elucidating mechanisms underlying seizure precursors and (3) implementing these algorithms on implantable hardware platforms. The notion of a preseizure state is catalyzing new clinical and basic science research, which has the potential to dramatically increase our understanding of epilepsy, and to generate exciting new therapies for patients.
162 citations
TL;DR: In Alzheimer's disease, recent advances have included the identification of behavioral profiles, differentiation of apathy and depression, and characterization of risk factors for dementia.
Abstract: Purpose of reviewNeuropsychiatric, or non-cognitive symptoms are increasingly recognized as manifestations of dementias.Recent findingsIn Alzheimer's disease, recent advances have included the identification of behavioral profiles, differentiation of apathy and depression, characterization of risk f
156 citations
TL;DR: Recognition of these methodological differences between animal and human studies has led to new trial design proposals, including better stratification of patients, a focus on moderate injury and earlier treatment, and larger sample sizes for clinical studies.
Abstract: Purpose of review Preclinical studies have shown that treatment to limit secondary cell damage can significantly improve outcome after traumatic brain injury. In contrast, neuroprotection trials in human traumatic brain injury have failed to convincingly demonstrate therapeutic benefit. Recent literature has begun to address this discrepancy between preclinical and clinical trials. Recent findings Perhaps the most important recent observations relate to the potential role of apoptosis in secondary brain injury. Because apoptosis peaks more than 24 h after injury, concepts about the therapeutic window for traumatic brain injury treatment have changed. Apoptosis and necrosis are in delicate balance and inhibition of one cell death pathway may enhance the other. This raises questions about the ultimate effectiveness of treatment strategies directed toward a single injury mechanism. In contrast to clinical head injury, which reflects a complex multi-factorial disorder, animal models are generally designed to address only a single injury component and are performed in genetically inbred animals of a single sex. Moreover, animal studies usually employ pretreatment or early posttreatment administration, examine moderate rather than severe injury, fail to examine brain drug levels or treatment optimization, and do not use an intent-to-treat methodology. Summary Recognition of these methodological differences between animal and human studies has led to new trial design proposals. For clinical studies, there should be better stratification of patients, a focus on moderate injury and earlier treatment, and larger sample sizes. Animal experiments should better parallel clinical studies and address therapeutic window and treatment optimization. Recognition of multiple cell death pathways should lead to new treatment strategies - including both combination drug treatment and drugs that affect multiple components of the secondary injury cascade.
140 citations
TL;DR: An increasing understanding of the pathogenetic mechanisms holds out promise for the effective treatment of diabetic neuropathy, and the early detection of abnormal glucose metabolism is particularly important, as treatments will probably be most effective if administered early in the course of the neuropathy.
Abstract: Purpose of reviewThis review will focus on recent advances in the field of diabetic neuropathy, with an emphasis on distal symmetric sensory and sensorimotor polyneuropathy. Some new information in the areas of diabetic amyotrophy and diabetic autonomic neuropathy will also be reviewed.Recent findin
133 citations
TL;DR: Recent findings question a simple CD4 T helper type 1 T cell paradigm and provide evidence for the role of various immune cells in the pathogenesis of experimental autoimmune encephalomyelitis and multiple sclerosis.
Abstract: Multiple sclerosis is characterized by demyelination and chronic inflammation of the central nervous system. Extensive studies in the animal model experimental autoimmune encephalomyelitis have suggested that multiple sclerosis is an autoimmune disorder mediated by myelin-specific CD4 T cells secreting T helper type 1 cytokines and tumor necrosis factor alpha. This concept has been widely used to develop new experimental therapies. However, recent findings in both experimental autoimmune encephalomyelitis and multiple sclerosis question a simple CD4 T helper type 1 T cell paradigm and provide evidence for the role of various immune cells in the pathogenesis of experimental autoimmune encephalomyelitis and multiple sclerosis. In this paper we review recent progress and discuss the implications for new therapeutic strategies.
TL;DR: New treatments to prevent development of Alzheimer's disease are targeting mild cognitive impairment as a treatment group and neurologists will increasingly be called upon to make this diagnosis.
Abstract: Mild cognitive impairment is an emerging term that encompasses the clinical state between elderly normal cognition and dementia. Controversy surrounds its characterization, implementation, and definition. Mild cognitive impairment is now the focus of natural history studies, biomarker studies, along with Alzheimer's disease prevention studies. The mild cognitive impairment stage may be the optimum stage at which to intervene with preventive therapies. Depending on the cohort source and definition, between 19 and 50% of mild cognitive impairment individuals progress to dementia (usually Alzheimer's disease) over 3 years. Despite controversy, progress has been achieved in defining risk factors for progression from mild cognitive impairment to dementia. New treatments to prevent development of Alzheimer's disease are targeting mild cognitive impairment as a treatment group and neurologists will increasingly be called upon to make this diagnosis.
TL;DR: In chronic inflammatory demyelinating polyradiculopathy differing clinical subtypes are beginning to emerge as has already occurred with the Guillain-Barre syndrome, but neither pathogenic correlates nor particular therapeutic approaches have yet been defined for these subgroups.
Abstract: In chronic inflammatory demyelinating polyradiculopathy differing clinical subtypes are beginning to emerge as has already occurred with the Guillain-Barre syndrome. However, neither pathogenic correlates nor particular therapeutic approaches have yet been defined for these subgroups. The neurophysiological techniques of terminal latency index and of modified F ratio help differentiate chronic inflammatory demyelinating polyradiculopathy from IgM paraproteinaemic neuropathy. Diagnosis may be assisted by magnetic resonance imaging studies in which enlarged nerve roots and plexuses and gadolinium enhancement may be evident. Further insight into pathogenesis has come from studies showing pathogenic antibodies in a small percentage of patients. Immunohistological studies examining the presence of adhesion, co-stimulatory and antigen presenting molecules in nerve biopsies have shown that T cell activation can be initiated and perpetuated within nerve and that Schwann cells possess the necessary markers to function as antigen presenting cells. Recent clinical trials have confirmed the therapeutic short term efficacy of intravenous immunoglobulin and Prednisone.
TL;DR: Mitochondrial dysfunction has gained considerable interest as a potential cause of epileptic seizures and therapy-resistant forms of severe epilepsy because mitochondria are intimately involved in pathways leading to the neuronal cell death characteristic for the areas of epileptogenesis.
Abstract: Mitochondrial dysfunction has gained considerable interest as a potential cause of epileptic seizures and therapy-resistant forms of severe epilepsy. Impairment of mitochondrial function has recently been observed in the seizure focus of human and experimental epilepsy. Additionally, a broad variety of mutation of mitochondrial DNA leading to the inhibition of mitochondrial respiratory chain or directly of mitochondrial adenosine triphosphate synthesis in epileptogenic areas of the human brain has been associated with epileptic phenotypes. Since mitochondrial oxidative phosphorylation provides the major source of adenosine triphosphate in neurons, and mitochondria participate in cellular Ca2+ homeostasis they can modulate neuronal excitability and synaptic transmission. Furthermore, mitochondria are intimately involved in pathways leading to the neuronal cell death characteristic for the areas of epileptogenesis.
TL;DR: Tentative clues as to the potential immunopathogenic mechanisms in acute transverse myelitis and related inflammatory disorders of the spinal cord have recently emerged, and a further understanding of how the immune system induces neural injury will depend upon confirmation and extension of these findings.
Abstract: Acute transverse myelitis is a group of disorders characterized by focal inflammation of the spinal cord and resultant neural injury Acute transverse myelitis may be an isolated entity or may occur in the context of multifocal or even multisystemic disease It is clear that the pathological substrate--injury and dysfunction of neural cells within the spinal cord--may be caused by a variety of immunological mechanisms For example, in acute transverse myelitis associated with systemic disease (ie systemic lupus erythematosus or sarcoidosis), a vasculitic or granulomatous process can often be identified In idiopathic acute transverse myelitis, there is an intraparenchymal or perivascular cellular influx into the spinal cord, resulting in the breakdown of the blood-brain barrier and variable demyelination and neuronal injury There are several critical questions that must be answered before we truly understand acute transverse myelitis: (1) What are the various triggers for the inflammatory process that induces neural injury in the spinal cord? (2) What are the cellular and humoral factors that induce this neural injury? and (3) Is there a way to modulate the inflammatory response in order to improve patient outcome? Although much remains to be elucidated about the causes of acute transverse myelitis, tantalizing clues as to the potential immunopathogenic mechanisms in acute transverse myelitis and related inflammatory disorders of the spinal cord have recently emerged It is the purpose of this review to illustrate recent discoveries that shed light on this topic, relying when necessary on data from related diseases such as acute disseminated encephalomyelitis, Guillain-Barre syndrome and neuromyelitis optica Developing a further understanding of how the immune system induces neural injury will depend upon confirmation and extension of these findings and will require multicenter collaborative efforts
TL;DR: Neurofibromas and schwannomas are benign peripheral nerve sheath tumours that occur as isolated sporadic lesions, but have their major clinical impact on the neurocutaneous diseases neurofibromaatosis 1 and neurof fibromatosis 2.
Abstract: Purpose of reviewNeurofibromas and schwannomas are benign peripheral nerve sheath tumours that occur as isolated sporadic lesions, but have their major clinical impact on the neurocutaneous diseases neurofibromatosis 1 and neurofibromatosis 2. The gene products neurofibromin and merlin (schwannomin)
TL;DR: The basic hypothesis is that over-expression of amyloid-β precursor protein within aging muscle fibers is an early upstream event causing the subsequent pathogenic cascade.
Abstract: Purpose of reviewSporadic inclusion-body myositis (s-IBM) and hereditary inclusion body myopathies are progressive muscle diseases that lead to severe disability We discuss recent advances in illuminating their pathogenic mechanism(s)Recent findingsWe emphasize how different etiologies might lead
TL;DR: An anatomical‐functional model as an operational framework is adopted in order to systematize the recent literature on emotional, behavioural and mood changes after stroke and prevent a complete understanding of emotional perception and behavioural responses in stroke.
Abstract: The brain mediates and integrates all cognitive activities, emotional experiences and finally behaviours. Stroke is undoubtedly a privileged disease for human behavioural studies, because of its high incidence. Recent advances in high-resolution magnetic resonance imaging techniques and functional neuroimaging allow both the precise localization of lesions and on-line visualization of the activity of cerebral areas and networks. Nevertheless, the neuropsychiatry of stroke remains uncertain in its relationship with brain dysfunction. Clinical studies on registry populations, single case studies, and functional neuroimaging data provide interesting findings, but differences in methods and great individual intervariability still prevent a complete understanding of emotional perception and behavioural responses in stroke. We adopted an anatomical-functional model as an operational framework in order to systematize the recent literature on emotional, behavioural and mood changes after stroke. The dysfunction of the areas subserving fundamental and executive functions induces behavioural and affective changes (such as depression, anxiety, apathy) that reflect the dysfunction of the whole system. Conversely, lesions in the system of instrumental functions induce signature syndromes (aphasia, anosognosia). At any delay from stroke, the diagnosis and treatment of mood and behavioural changes are a priority for clinicians and healthcare professionals to improve the quality of life of patients.
TL;DR: Advances in neuroimaging and in genetic and other laboratory testing approaches have resulted in an increased definition of stroke subtypes and risk factors, which have led to an enhanced understanding of the multiple risk factors underlying childhood stroke.
Abstract: Childhood stroke is emerging as a serious and frequent disorder. In contrast to adult stroke, the study of childhood stroke is in a very early stage of research development with no randomized controlled trials conducted to date outside of sickle cell stroke. The results of research in adults have limited applicability to children with stroke due to fundamental age-related differences in the neurological, cerebrovascular and coagulation systems. In recent years clinical and basic research studies have improved our understanding of childhood stroke. Population-based studies have resulted in an increased awareness of the frequencies and features of stroke syndromes in children. Cohort and case-control studies have led to an enhanced understanding of the multiple risk factors underlying childhood stroke. Advances in neuroimaging and in genetic and other laboratory testing approaches have resulted in an increased definition of stroke subtypes and risk factors.
TL;DR: It is taken that chronic daily headache is what it says ‐ frequent headache, and hematologists make a diagnosis of anemia, which invites further investigation and sub‐classification, neurologists might diagnose chronic daily headaches not to imply that all its causes are the same but simply to begin the clinical process.
Abstract: Systematic scientific classification of primary headaches is inexact, relying on clinical features because the disorders lack diagnostic markers, although the International Headache Society classification has been successful in providing relatively homogenous clinical groups for pathophysiological and therapeutic studies. One area in which there have been particular difficulties and uncertainty is in classifying patients with frequent headache, particularly chronic daily headache. Clinical research on the topic is limited, and imprecise because of uncertainties of definition. Rigorous basic or applied clinical research is a rarity, attested to by a paucity of new publications in the past year. Accordingly, the scientific basis of chronic daily headaches remains to be determined. There is agreement on one issue: for headache specialists and neurologists this is an important clinical problem. We take the position that chronic daily headache is what it says--frequent headache. As hematologists make a diagnosis of anemia, which invites further investigation and sub-classification, neurologists might diagnose chronic daily headache not to imply that all its causes are the same but simply to begin the clinical process.
TL;DR: Interest has grown in treatment of multiple sclerosis‐related erectile failure, and female sexual dysfunction is also now gaining some attention, with new classification criteria and methods for assessing and treating these patients.
Abstract: The fundamental strategy in treating multiple sclerosis patients with unstable bladders involves a combination of suppressing urgency and ensuring effective urinary drainage. Anticholinergics remain the first-line treatment, but alternative therapies are undergoing clinical trials. With a range of new proerectile oral medications available, interest has grown in treatment of multiple sclerosis-related erectile failure. Female sexual dysfunction is also now gaining some attention, with new classification criteria and methods for assessing and treating these patients.
TL;DR: Qualitative lesion analysis in stroke patients indicates the importance of cortical regions such as the intraparietal sulcus and the middle frontal gyrus for subserving praxic function in apraxia.
Abstract: Impairments in praxic functioning are common after stroke, most frequently when the left hemisphere is affected. Several recent studies of apraxia after stroke have made advances in understanding the right hemisphere contribution to praxis, particularly for the performance of novel actions. Moreover, quantitative lesion analysis in stroke patients indicates the importance of cortical regions such as the intraparietal sulcus and the middle frontal gyrus for subserving praxic function. Complex neuropsychological models have been developed to account for the many dissociations observed in the types of errors observed in stroke patients. Relatively lacking, however, are models that attempt to relate the neurological data to what is known about praxis from functional neuroimaging in normal subjects and from physiological studies in the monkey. Moreover, a coherent interpretation of the results of apraxia studies remains hampered by the lack of a standard testing instrument to assess the nature and severity of apraxic impairments in the groups tested.
TL;DR: The present review summarizes data on neurologic complications following vaccination, and provides evidence that indicates whether they were directly associated with the vaccines, and claims that complications are caused by adjuvants, preservatives and contaminants.
Abstract: Public tolerance to adverse reactions is minimal. Several reporting systems have been established to monitor adverse events following immunization. The present review summarizes data on neurologic complications following vaccination, and provides evidence that indicates whether they were directly associated with the vaccines. These complications include autism (measles vaccine), multiple sclerosis (hepatitis B vaccine), meningoencephalitis (Japanese encephalitis vaccine), Guillain-Barre syndrome and giant cell arteritis (influenza vaccine), and reactions after exposure to animal rabies vaccine. Seizures and hypotonic/hyporesponsive episodes following pertussis vaccination and potential risks associated with varicella vaccination, as well as vaccine-associated paralytic poliomyelitis following oral poliovirus vaccination, are also described. In addition, claims that complications are caused by adjuvants, preservatives and contaminants [i.e. macrophagic myofasciitis (aluminium), neurotoxicity (thimerosal), and new variant Creutzfeldt-Jakob disease (bovine-derived materials)] are discussed.
TL;DR: This review provides an update on the current understanding of the pathogenesis of Guillain-Barre syndrome and progress has been made in elucidating relevant pathomechanisms, especially in the axonal variants of the disease.
Abstract: This review provides an update on the current understanding of the pathogenesis of Guillain-Barre syndrome (GBS). Progress has been made in elucidating relevant pathomechanisms, especially in the axonal variants of the disease. However, the precise target autoantigens still need to be determined. Future therapeutic approaches and currently available strategies are critically discussed.
TL;DR: The conclusions have been that the most recent evidence does not support Robinson's influential neuroanatomical model, assuming that a left frontal stroke could provoke a major PSD, indistinguishable from the functional forms of major depression.
Abstract: Post-stroke depression (PSD) is a very frequent and important consequence of stroke, but, in spite of the high number of papers aiming to clarify various aspects of this disorder, controversies about its incidence, its (biological or psychological) determinants, its consequences and its treatment still persist. In the present survey we have taken separately into account each of these issues, starting from a critical discussion of the main factors which can affect the estimates of the incidence of PSD. We have then surveyed and updated the debate between proponents of a neuroanatomical and a psychological interpretation of PSD. Our conclusions have been that the most recent evidence does not support Robinson's influential neuroanatomical model, assuming that a left frontal stroke could provoke a major PSD, indistinguishable from the functional forms of major depression. In the section devoted to the consequences of PSD, we have particularly taken into account the problem of the deleterious influence that PSD could have on functional recovery. The available evidence does not allow us to conclude if an improvement of PSD also leads to an improvement of the patient's functional status. As for the therapy of PSD, a pharmacological treatment with selective serotonin reuptake inhibitors has proven effective and safe, whereas psychological methods of treatment of patients and their families have not yet given conclusive results.
TL;DR: The recent mapping of additional dystonia gene loci, the identification of novel dySTONia genes, and the characterization of proteins encoded by these genes have enhanced the understanding of various forms and aspects of the dystonias and have opened up new avenues for research.
Abstract: Purpose of reviewThe present review covers recent advances in dystonia research related to dystonia genetics and treatment. These have led to the discovery of novel dystonia genes and loci, to changing classification schemes, and to the introduction of improved and new treatment options.Recent findi
TL;DR: The multi‐infarct model and the Alzheimer's model of dementia are gradually being replaced by a much broader concept of vascular cognitive impairment, which reflects a more profound understanding of the pathogenic mechanisms that underlie this complex syndrome.
Abstract: The concept of vascular dementia is undergoing revision The multi-infarct model and the Alzheimer's model of dementia, usually referred to as 'multi-infarct dementia', are gradually being replaced by a much broader concept of vascular cognitive impairment This conceptual evolution reflects a more profound understanding of the pathogenic mechanisms that underlie this complex syndrome As a consequence of this revision new diagnostic criteria have been established during the past 25 years, resulting in new problems with regard to precise disease definition and limited inter-rater reliability The particular criteria chosen by a clinician or investigator to diagnose vascular dementia have a major impact on epidemiology, disease management and health economic estimates
TL;DR: Assessment of the clinical features suggests that an accuracy of 90% may be the highest that can be expected using current diagnostic criteria for Parkinson disease.
Abstract: Parkinson disease is a slowly progressive neurodegenerative disorder with a varied clinical picture and a variable rate of progression. Recently, there have been some studies conducted to assess the diagnostic accuracy and other clinical aspects of the disease. In the absence of a biomarker the clinical diagnosis is imprecise. This leads to a significant number of misdiagnoses, especially in early disease. Assessment of the clinical features suggests that an accuracy of 90% may be the highest that can be expected using current diagnostic criteria. In addition to bradykinesia, which is a core symptom, different types of tremors occur. Whereas the rest tremor is characteristic, action tremor, re-emergent tremor and orthostatic tremor may occur in Parkinson disease. Symptomatic treatments are quite effective in early disease but clinical course is complicated by the appearance of motor fluctuations and dyskinesias in more advanced disease. Non-motor complications, such as cognitive, psychiatric and autonomic problems, become bothersome and disabling in some patients.
TL;DR: The present review describes advances in Rasmussen's encephalitis, an unihemispheric intractable epileptic disease with persistent inflammation, with specific attention to the recent recognition of cytotoxicity by CD8+/granzyme-B-positive T lymphocytes as a new pathogenic mechanism of neuronal damage.
Abstract: The present review describes advances in Rasmussen's encephalitis (also known as Rasmussen's syndrome), an unihemispheric intractable epileptic disease with persistent inflammation. Specific attention is given to the recent recognition of cytotoxicity by CD8 + /granzyme-B-positive T lymphocytes as a new pathogenic mechanism of neuronal damage.
TL;DR: NO synthase and the NO production site have been localized using immunohistochemistry and a new fluorescence indicator for NO to suggest that excessive NO production may play an essential role in inner ear disorders.
Abstract: During the past year significant advances have been made in our understanding of the functional significance of nitric oxide (NO) in the inner ear. NO synthase and the NO production site have now been localized using immunohistochemistry and a new fluorescence indicator for NO. The functional significance of NO in the inner ear, in particular as a neurotransmitter, is becoming increasingly clear. Increasing evidence suggests that excessive NO production may play an essential role in inner ear disorders. The production of an inducible form of NO synthase may be closely related to this phenomenon. Based on the mechanisms of inner ear disorders, new pharmacological strategies for preventing or treating inner ear disorders have been suggested.