Showing papers in "Current Opinion in Neurology in 1996"

Mechanisms and management of fatigue in progressive neurological disorders.

Abstract: Fatigue in neurologic disorders has been examined in several important studies over the past year. These reports suggest that fatigue is a common and often profoundly debilitating symptom. Assessment and treatment of fatigue requires a multidisciplinary approach.

Oxidative Stress and Mitochondrial Dysfunction in Neurodegeneration

Abstract: Rapid advances are being made in our understanding of the pathogenesis of neurodegenerative diseases, particularly those in which specific DNA mutations have been identified. beta-amyloid has been shown to induce free radical formation both directly and via an effect on endothelial function. There is presuasive evidence for cytochrome oxidase dysfunction with oxidative stress and damage in the brains of patients with Alzheimer's disease. The confirmation of the complex II inhibitor 3-nitropropionic acid as a toxin model for Huntington's disease, together with the demonstration of reduced mitochondrial function in Huntington's disease caudate, supports the proposition that mutant huntingtin may exert its effect through an abnormality of energy metabolism.

Reflex hyperexcitability and muscle contracture in relation to spastic hypertonia

Abstract: Mechanisms of spasticity and possible therapeutic interventions continue to dominate research into motor disorders following cerebral lesions. However, the accumulated evidence suggests that this focus on spasticity may be out of step with its effects. In contrast, hypertonia remains an important problem. Further investigation into its link with muscle contracture is required and it needs to be clearly distinguished from reflex hyperexcitability in patients with spasticity.

Virtual reality: an assistive technology in neurological rehabilitation.

Abstract: The need for improved neurological rehabilitation strategies is self-evident. Recent developments in the computer technology of virtual reality hold the promise of exciting progress in this area. In this paper four areas of potential application of virtual reality to neurological rehabilitation are reviewed.

Familial amyloid polyneuropathy : new developments in genetics and treatment

Abstract: Familial amyloid polyneuropathy is an hereditary amyloidosis related to several different genetic errors. It usually presents as a severe peripheral neuropathy. The protein most frequently involved in the disease is transthyretin, a serum transport protein synthesized primarily in the liver. Variabl

Epilepsy in patients with central nervous system tumors.

Abstract: Seizure is often the first manifestation of a central nervous system tumor; such tumors are often responsible for pharmacologically refractory seizures. The treatment of tumor-associated epilepsy should, on one hand, follow sound neuro-oncological principles and, on the other hand, control the epile

Genetics of movement disorders

Abstract: Trinucleotide repeat expansions or unstable mutations are the cause of a growing number of hereditary movement disorders, especially inherited ataxias. Diagnostic practice as well as disease classifications have altered accordingly. Genes responsible for "Parkinsonian plus' syndromes and episodic movement disorders have also been recently mapped.

The immunopathogenesis of multiple sclerosis and guillain-barre syndrome

Abstract: This review covers current hypotheses regarding antigen-specific disease induction, immune responses within the central and peripheral nervous systems, the nonspecific inflammatory cascade, and mechanisms responsible for demyelination, axonal loss, and disease progression in multiple sclerosis and Guillain-Barre syndrome. We also discuss the new evidence on the role of infection as an aetiological factor in multiple sclerosis and Guillain-Barre syndrome.

Neurotoxicity of beta-amyloid and prion peptides.

Abstract: Neuropathological observations, supported by genetic and biochemical studies, indicate the central role of amyloid-beta protein deposits in the pathogenesis of Alzheimer's disease. In prion-related encephalopathies also, an altered form of prion protein forms amyloid fibrils and accumulates in the brain. In both conditions the amyloid deposition is accompanied by nerve cell loss, the pathogenesis and molecular basis of which are not understood. Synthetic peptides homologous to amyloid-beta protein and its fragments and to prion protein fragments are utilized to investigate the mechanisms of cerebral deposit formation and the role played by these proteins in Alzheimer's disease and prion-related encephalopathies, respectively. Amyloid-beta protein peptides have been shown to be neurotoxic and amyloidogenic under experimental conditions and numerous studies have been performed to clarify the mechanism of neuronal death induced by exposure to these peptides. Peptides homologous to the fragment 106-126 of prion protein, an integral part of all abnormal prion protein isoforms that accumulate in the brain of patients with prion-related encephalopathies, are neurotoxic, fibrillogenic, and have a secondary structure largely composed of beta-sheet and proteinase-resistant properties.

Spectrum of memory dysfunction in degenerative disease

Abstract: We have summarized relevant literature on the patterns of memory deficit found in Alzheimer's disease, the focal lobar atrophies (semantic dementia and dementia of frontal type) and three forms of subcortical dementia (progressive supranuclear palsy, Huntington's and Parkinson's disease). We have st

The effects of seizures on the brain.

Abstract: Since the time of Sommer's review of hippocampal pathology and Gower's tenet that' seizures beget seizures' there has been interest in changes in brain structure and function that may be associated with epilepsy. From recent experimental studies and clinical observations, there is increasing evidence that epilepsy is not only associated with structural and functional alterations in the nervous system, but also that seizures induce a diverse variety of molecular, cellular, and functional alterations in the brain.

Craniosynostosis: novel insights into pathogenesis and treatment.

Abstract: The identification in craniosynostosis syndromes of mutations in genes belonging to the fibroblast growth factor signalling pathway and the transcriptional regulator MSX2 provides important clues to the pathogenesis of these disorders. Although surgery continues to be the mainstay of treatment, new animal models and improved uncerstanding of cranial suture biology and pathology may lead to complementary therapies.

The immunopathologic and inflammatory differences between dermatomyositis, polymyositis and sporadic inclusion body myositis.

Abstract: In polymyositis and sporadic inclusion body myositis, clonal expansion of CD8+ cells which are primed to recognize previously unknown muscle antigens occurs. Compared with sporadic inclusion body myositis, however, in which the T-cell response may not be antigen driven, there is in polymyositis an overexpression of certain T-cell receptor gene families among the autoinvasive T-cells. Although studies on the endomysial expression of cytokines and cell adhesion molecules have provided additional support for the concept of an ongoing immune process, the site of sensitization and the mechanism by which the autoimmune process is triggered remains to be established. In dermatomyositis, a multiorgan disease, evidence exists that the complement-mediated microvascular injury by the putative antibody may not be limited to the endomysial vessels but may also involve the blood vessels in the dermis. The antigenic target on the endothelial cell in dermatomyositis patients and the pathogenic role of the recently studied anti-Mi-2 antibody directed against a helicase are still to be determined.

Magnetic resonance imaging in the differential diagnosis and monitoring of the treatment of multiple sclerosis.

Abstract: Treatments with potentially beneficial effects on the course of multiple sclerosis are now emerging and magnetic resonance imaging techniques are needed which have a high specificity for diagnosing multiple sclerosis, and which can characterize the heterogeneous nature of multiple sclerosis lesions and define disease evolution over time. Differential diagnosis may be improved by the use of gadolinium-enhanced magnetic resonance imaging, high-resolution spinal cord and optic nerve magnetic resonance imaging and non-conventional magnetic resonance imaging techniques. In the monitoring of treatment, a number of different approaches have been used to increase magnetic resonance imaging accuracy in describing and predicting disease activity and evolution. These include optimization of the acquisition and post-processing of data obtained with conventional magnetic resonance imaging techniques (T2-weighted and postcontrast T1-weighted sequences) and the use of newer nonconventional magnetic resonance imaging techniques.

Advances in the molecular genetics of the limb-girdle type of autosomal recessive progressive muscular dystrophy

Abstract: A reclassification of the limb-girdle types of autosomal recessive muscular dystrophy based on genetic and protein information has been made possible by major advances over the past 2 years. At least six different forms of limb-girdle types of autosomal recessive muscular dystrophy can be defined by their genetic basis, with at least two pathogenic mechanisms involved. Three forms are defined by involvement of different proteins of the sarcoglycan complex, while a muscle specific protease (calpain 3) is implicated in another form of the recessive disease. These findings provide the basis for a new diagnostic approach to the group, with molecular techniques now an essential part of the diagnostic process. A scheme for diagnosis in this group is proposed.

Presenile because of presenilin: the presenilin genes and early onset Alzheimer's disease.

Abstract: Alzheimer's disease is a neurodegenerative disorder characterized by the massive and invariant accumulation of amyloid plaques in the brains of affected patients. In many cases Alzheimer's disease occurs in the absence of a prior history of the disease in other family members and is designated as sporadic, whereas in approximately 10% of patients, dominantly transmitted mutations within one of three genes are found. A few mutations have been identified within the gene encoding the beta-amyloid precursor protein; however, these mutations account for only about 1-3% of cases with familial Alzheimer's disease. In the majority of autosomal dominant cases (40-50%), mutations have been found in a gene localized to chromosome 14. The responsible gene, now called presenilin-1, has recently been identified and shown to encode a putative seven transmembrane domain protein. Surprisingly, a second highly homologous gene (named presenilin-2) was cloned shortly thereafter. It is localized on human chromosome 1 and is also involved in a small number of cases with familial Alzheimer's disease. Early data suggest that mutations found within the two genes cause early onset Alzheimer's disease by influencing the proteolytic processing of amyloid beta-peptide in a pathological manner.

Inflammation in AIDS and the role of the macrophage in brain pathology.

Abstract: HIV-associated dementia complex is the most severe neurologic complication of AIDS. The pathologic substrate of the complex, termed HIV encephalitis, is marked by abundant infection and activation of brain macrophages. The pathogenesis of neurologic damage in HIV encephalitis is essentially undefined. Most current investigations are focused on potential viral or macrophage neurotoxins.

Central nervous system cell transplantation: a novel therapy for storage diseases?

Abstract: Many methods of gene transfer to the brain are under study. One employs a neural stem cell based strategy. Transplanting neural progenitor cells that intrinsically secrete missing or therapeutic gene products, or are genetically engineered ex vivo to do so, may provide a strategy for long-term treatment of central nervous system manifestations of a number of neurogenetic diseases. Multipotent neural progenitors or stem cells (or cells that mimic their behavior) are capable of differentiating along multiple central nervous system cell-type lineages. They can engraft as integral members of normal structures throughout the host central nervous system without disturbing other neurobiological processes. They can also be easily genetically manipulated ex vivo. By exploiting their basic biological properties, these cells may be able to deliver therapeutic gene products in a sustained, direct, and perhaps regulated fashion throughout the central nervous system. Furthermore, although they may disseminate these gene products throughout the brain, they nevertheless restrict that distribution to only the central nervous system. Thus, these vehicles may overcome many of the limitations of viral and non-neural cellular vectors, as well as pharmacologic and genetic interventions. The feasibility of this neural stem cell-based strategy has been demonstrated by correcting the widespread central nervous system pathology of a murine model of a prototypical inherited neurodegenerative disease, mucopolysaccharidosis type VII. These studies have helped to establish the use of such cells as a paradigm for transferring other molecules of therapeutic or developmental interest throughout the central nervous system at many ages.

Apolipoprotein E in neurology.

Abstract: Apolipoprotein E became relevant for neurologists in 1993 when the association of the apolipoprotein E-epsilon 4 allele with familial and sporadic late-onset Alzheimer disease was reported. Since that time, more than 100 confirmations and many research papers have appeared. A large neurobiological literature concerning the role of apolipoprotein E in the metabolism of the central nervous system is developing.

Physician and patient-oriented outcomes in progressive neurological disease: which to measure?

Abstract: Outcomes can be described as either physician or patient-oriented depending on whose perspective is adopted. Both perspectives offer different yet complementary information. Traditionally, the effectiveness of interventions has been evaluated in terms of physician-oriented outcomes. recently there has been a growing recognition of the importance of the patient's point of view in assessing the outcomes of medical care. This is now held to be central to the monitoring and evaluation of health care. This review describes these two perspectives and compares the nature of the information provided by each.

Primary and secondary stroke prevention.

Abstract: Recent clinical trials have demonstrated that we can prevent stroke with appropriate medical and surgical therapy. Treatment of stroke risk factors, antiplatelet therapy, anticoagulant therapy, and carotid endarterectomy have all proven to be effective if applied in appropriate clinical circumstances. This review will highlight the areas in which we have clinical trial evidence to guide us, and will point out those circumstances in which uncertainty remains.

Stroke in children and young adults

Abstract: This selective review of stroke in children and young adults addresses: (1) stroke in sickle cell disease, particularly the prognostic use of transcranial Doppler, (2) oral contraceptives as a stroke risk factor, (3) stroke in pregnancy, and (4) the prognosis of ischemic stroke in young adults Factors relevant to the primary prevention and outcome of stroke are emphasized

The mortality of epilepsy.

Abstract: The overall risk of premature death in patients with epilepsy has recently been quantified and is two to three times that of the general population. Most of the increased risk is directly related to the cause of the epilepsy itself. A small number of deaths in the general population of patients with epilepsy are epilepsy-related deaths, which includes those deaths caused by a seizure or accidents during or immediately after a seizure, as well as sudden unexpected death, for which no cause of death can be identified. Sudden unexpected deaths are more common in patients with intractable epilepsy. Recent studies suggest that improved seizure control, advice and help to avoid the hazards that occur during a seizure, as well as increased supervision of institutionalized patients, may help reduce the risks of epilepsy-related death occurring.

Current diagnosis and treatment of central nervous system germ cell tumours.

Abstract: Central nervous system germ cell tumours can be cured with high quality posttreatment neuropsychological and endocrinological measures. In order to firmly establish a histological diagnosis, surgery is essential. Management should be planned precisely according to histological and biological malignancy and the extent of the disease. Patients with germinoma can be cured by preirradiation chemotherapy followed by reduced dose irradiation.

Dementia with lewy bodies

Abstract: Dementia with Lewy bodies is a generic term which was proposed at the first International Workshop on Lewy Body Dementia (Newcastle upon Tyne, 1995). It is an all encompassing term that includes various types of disorder such as diffuse Lewy body disease, senile dementia of Lewy body type, and Lewy body variant of Alzheimer's disease. Epidemiological, clinical, neuropathological, biochemical, molecular biological, and therapeutic contributions to the understanding of dementia with Lewy bodies are reviewed.

Headache caused by raised intracranial pressure and intracranial hypotension.

Abstract: Extremes of intracranial pressure commonly cause headache. Benign intracranial hypertension is a rare syndrome of increased intracranial pressure manifesting as headache, intracranial noises, transient visual obscuration, and palsy of the sixth cranial nerve. Endocrine disorders such as obesity and hypoparathyroidism, hypervitaminosis A, tetracycline use and thyroid replacement are probable causes of benign intracranial hypertension. In the majority of cases, however, it is idiopathic. Benign intracranial hypertension is though to be caused by cerebral edema, high cerebrospinal fluid outflow resistance and high cerebral venous pressure, or a combination of the three. The management of benign intracranial hypertension includes, symptomatic headache relief, removal of offending risk factor(s), and medical or surgical reduction of intracranial pressure. Spontaneous intracranial hypotension is more rare than benign intracranial hypertension. Postural headache (worse in the upright position) is the hallmark of spontaneous intracranial hypotension. Typically, the cerebrospinal fluid pressure is less than 60 mm H2O. Diminished cerebrospinal fluid production, hyperabsorption, and leak are postulated mechanisms of spontaneous intracranial hypotension. Empirical treatment includes bed rest, administration of caffeine, corticosteroids or mineralocorticoids, epidural blood patch, and epidural saline infusion.

Rasmussen's encephalitis : an autoimmune disorder?

Abstract: Rasmussen's encephalitis is a rare progressive pediatric epileptic syndrome. Recent evidence from experimental animals and patients with the disease suggests an important role for both humoral- and cell-mediated immune mechanisms in the pathogenesis of this disease. The glutamate receptor subunit, GluR3, may be an important autoantigen in the disease.

Chronic inflammatory polyneuritis and neuropathies.

Abstract: This review deals with recent developments in chronic inflammatory polyneuropathies which, for the most part, are now amenable to effective treatments including immunosuppressive agents, therapeutic plasmapheresis, high-dose intravenous immunoglobulins and possible interferon-beta. Cell- and antibody-mediated mechanisms are discussed and interpreted against the background of experimental autoimmune neuritis. Antibodies of the immunoglobulin G and immunoglobulin M class have been described directed at various peripheral nervous system antigens. There is now ample evidence that some antibodies influence nerve function by mechanisms other than demyelination. Despite considerable overlap of clinical signs between idiopathic chronic inflammatory demyelinating polyradiculoneuropathy and chronic polyneuritis associated with monoclonal gammopathies or malignancies, we suggest maintaining the traditional separation rather than lumping them together. Some distinctive features have now been elaborated including presentation and response to treatment. Multifocal motor neuropathy is a separate disorder with a multifocal inflammatory demyelinating pathology resembling chronic inflammatory demyelinating polyradiculoneuropathy.

Deletion of the PMP22 gene and hereditary neuropathy with liability to pressure palsies.

Abstract: Deletion of the 1.5 Mb tract on chromosome 17p11.2-12 that is duplicated in Charcot-Marie-Tooth disease type 1A is commonly associated with hereditary neuropathy with liability to pressure palsies. The deletion, which originates from an unequal meiotic crossover involving two homologous repeats, causes underexpression of the peripheral myelin protein gene PMP22. PMP22 frameshift and non-sense mutations can be found in the rare nondeleted cases. Targeted disruption of the PMP22 gene in mice has provided an animal model for the disease. Current studies are aimed at characterising the genetics of this chromosomal rearrangement and the pathogenic role of altered PMP22 expression.

New aspects of migraine pathophysiology: lessons learned from positron emission tomography.

Abstract: Recent positron emission tomography investigations found spreading oligemia in the early phases of a human migraine attack. During the headache phase, increased cerebral blood flow was found in cortical sensory association areas and unilaterally in the brainstem. The brainstem activiation persisted