Multiple Sclerosis Homeopathic Treatments

Proven MS Treatment By Dr Gary Levin

The healing process is done by using a simple step-by-step method that rehabilitates your immune system and boosts supporting body systems to get rid of all symptoms (and types) of Multiple Sclerosis Plus re-energizes and purifies your body for maximum health. In my step-by-step Treatment System, you'll learn how my Directed Nutrition method plus a special vitamin regimen will significantly reduce your symptoms and eventually completely rid you of your current condition. It shouldn't be any surprise to people that directed nutrition and simple plants and vitamins can be the basis for powerful cures. Contrary to popular belief, even prescription drugs aren't wholly manufactured from synthetics. Often a rare plant, available only in the rain forests of the Amazon, is the basis of powerful prescription medications. And don't forget that your body is Made From natural materials and incorporates a system that uses natural products such as food to constantly rebuild and heal. Continue reading...

Proven MS Treatment By Dr Gary Levin Summary

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Description Of Multiple Sclerosis

An important feature of multiple sclerosis is the marked variability in neurologic symptoms and clinical course. Four different types of disease course have been described. Most patients present with relapsing-remitting disease. An individual develops neurologic symptoms and signs over hours to days and typically recovers in 6-8 weeks. This is followed by various lengths of disease-free periods. Some individuals have few relapses and no residual symptoms, whereas others have frequent relapses and accumulating disability. Approximately one-half of the patients with relapsing-remitting disease go on to develop secondary progressive disease. In this case, features of relapsing-remitting disease are followed by a gradual decline in function with or without superimposed relapses. Primary progressive disease, which affects 10-15 of individuals with MS, is characterized by a gradual decline in neurologic condition from onset, without relapses. This form of disease progression is typically...

Multiple Sclerosis

Multiple sclerosis (MS) is a neurologic disorder that causes variable motor, sensory, visual, and cerebellar dysfunction due to multifocal areas of CNS myelin destruction. Paresthesias, gait difficulty, extremity weakness, poor coordination, and visual disturbances occur most often with a relapsing and remitting clinical course. Despite the lack of a definitive cure, immunosuppression and immunomodulation provide adequate symptomatic therapy in the majority of patients. Most patients with MS sustain only mild to moderate lifetime morbidity without a reduction in overall life expectancy.

What is the difference between an intervention in a clinical trial and in an observational study

The major goals of medical treatment are to reduce or eliminate the symptoms and signs of a disease, to slow or halt disease progression, or to prevent specific complications, including premature death. The natural history of most diseases is unpredictable in individual patients. Several acute conditions such as the common cold are self-limiting other diseases such as multiple sclerosis are often intermittent with unpredictable remissions. The time course of many chronic conditions is highly variable and the risk of complications of degenerative conditions such as atherosclerosis is unpredictable, although one can differentiate between low- and high-risk subjects. Consequently, distinguishing between real treatment effects and the natural course of a disease can be a major challenge. By using comparable groups of study subjects in a clinical trial, one receiving the new treatment and the other not, we are able to make a good estimate of both favorable and unfavorable treatment effects.

Polymers Could Be the Most Broadly Applicable Multivalent Ligands

Copaxone (glatiramer acetate), marketed by Teva Pharmaceuticals (Israel), is an example of a highly successful polymer therapeutic 163 . Glatiramer acetate is a large (average MW 5-11 kDa) synthetic polypeptide of l-Ala, l-G1u, l-Lys, and l-Tyr (a mimic of myelin basic protein) that is random in distribution but defined in composition 164 . It has been approved for the treatment of patients with re-lapsing-remitting multiple sclerosis (RR-MS reducing the frequency of relapses and disease progression in clinical studies) 165 . While the exact mechanism of action is unknown, the polypeptide is known to attenuate patients' autoimmune response to myelin and to reduce both the inflammation and neurodegeneration associated with the disease 164 . An oral form of glatiramer acetate is effective in the treatment of models of MS in vivo (rodents and primates) 166, 167 . It has not yet, however, shown statistically significant results in human clinical trials (as of 2005, Phase II clinical...

Demyelinative Diseases

This group of diseases has long been the most familiar of all the white matter disorders. Multiple sclerosis is the prototype white matter disease of the central nervous system, affecting the spinal cord as well as the brain, and has been a major clinical and research interest of neurologists since the time of Jean Marie Charcot, who made many important observations about the disease in the late 19th century. In part because they tend to affect patients at early stages in life, demyelinative diseases are a significant source of neurologic disability. Study of these diseases has also been stimulated by the likelihood that their pathogenesis can shed light on many aspects of neural dysfunction.

Anatomical Changes With

White Matter Hyperintensities With the advent of MRI, abnormal signals were observed in the white matter in a number of neurological diseases known to affect the white matter (e.g., multiple sclerosis and Binswanger's disease), in various dementias, as well as in the elderly. Because these MRI signals are often best observed using scanning parameters that result in their appearing as bright lucencies against a black (low-signal) white matter, they have been termed white matter hyperintensities (WMHs). Two kinds have been distinguished (i) Periventricular white matter hyperintensities (PWMHs) appear either as frontal or occipital caps of the cerebral ventricles or as a thin lining surrounding the ventricles, and (ii) deep white matter hyperintensitites (DWMHs) are seen as subcortical punctate foci, although larger confluences of foci form with increased severity and often merge with the PWMHs. The neuropathological substrate for these signals can vary depending on the disease. In...

Neurological Abnormalities

Ing dysfunction include CVEs, cauda equina syndrome or spinal cord compression, Parkinson's disease, Shy-Drager syndrome (multisystem atrophy), multiple sclerosis (MS), and motor neuron disease (MND). Spinal cord injury also causes long-term voiding dysfunction, but rarely AUR. Most patients are, however, managed with an in-dwelling catheter after the initial injury, until the period of spinal shock has passed when a better idea of long-term bladder function can be ascertained.

Disregulatory Conditions

Multiple sclerosis is another condition that in 710 of patients leads to PLC, sometimes with euphoria. Characteristics of so-called pseudobulbar palsy associated with multiple sclerosis (as with bilateral strokes) include dysarthria, dysphagia, bifacial weakness, and weak tongue movements but preserved coughing, yawning, laughing, and crying.

Central nervous system

Multiple sclerosis Multiple sclerosis (MS) is characterized by areas of myelin destruction in the central nervous system known as plaques. Central nervous system myelin is made by oligodendrocytes and as the illness progresses oligodendrocytes come to be lost. In addition, axons coursing through areas of demyelination may be destroyed, particularly in the later stages of the disease. Multiple sclerosis is an inflammatory disease. B cells, macrophages, and CD4' and CD8 ' T cells are found within and at the margins of active plaques. All these cell types are activated the B cells synthesize IgG which exhibits oligoclonal restrictions, the macrophages release interleukin 1 (II.-1), tumor nccrosis factor a (TNFa), and IL-6. The CD4 T cells are chiefly of the Tnl cell subset. They secrete IL-2, IFNy and lymphotoxin (LT), all of which are found in active MS plaques. The mainstay of treatment of multiple sclerosis attacks is glucocorticoid therapy. One popular treatment regimen is...

Individual Adjustment and Well Being

In outpatient clinics and mental health centers, practically any CBT can be modified and applied for use in individual and group formats with community-residing persons with disability. There are situations in which individual CBT may be preferred over group interventions. For example, individualized CBT for depressed persons with multiple sclerosis may be more effective than group interventions because the practitioner can tailor strategies to the unique needs of the progressively degenerative symptoms experienced by the individual (Mohr, Boudewyn, Goodkin, Bostrom, & Epstein, 2001). However, assertion and other interpersonal skills may be best taught in group formats (Glueckauf & Quittner, 1992). These skills have long been recognized as essential in navigating tense interpersonal encounters and in managing the debilitating social stigma associated with visible disability. Social skills training is associated with greater well-being, mobility, and acceptance of disability...

An estimated 2 million cases of traumatic brain injury TBI

Occur in the United States every year, with around 500,000 sufficiently serious to require hospitalization. Additionally, a large number of cases of mild TBI remain unreported or undiagnosed each year. Therefore, TBI, with its estimated incidence of 100 per 100,000 persons, occurs more often than many of the better known diseases affecting the central nervous system tissue (e.g., Parkinson's disease, Alzheimer's disease, multiple sclerosis). Epidemiologically, TBI is most often associated with motor vehicle, bicycle, or pedestrian-vehicle accidents followed by falls and violence- and sports-related incidents, occuring primarily in people 15-24 years of age. Estimates for the lifetime cost of care for a severely injured person range from 600,000 to 1,875,000 and add up to a yearly cost of 9-10 billion for rehabilitation for new cases in the Unites States alone. Although the development of

Role of Methylation in Organisms

Against myelin basic protein was detected in patients with multiple sclerosis diseases. Chuikov et al. (2004) found a novel mechanism to regulate p53 function through lysine methylation by Set9 methyltransferase. Set9 specifically methylates p53 at one residue within the C-terminus regulatory region. Methylated p53 is restricted to the nucleus, and the modification positively affects its stability. Set9 regulates the expression of p53 target genes in a manner dependent on the p53-methylation site. The crystal structure of a ternary complex of Set9 with a p53 peptide and the cofactor product provides the molecular basis for recognition of p53 by this lysine methyltransferase.

Toxicity and tolerability

Because the role of chemokine receptors in natural inflammatory and immune responses is not fully understood, the impact of manipulating these systems is considered uncharted territory. There is an experiment of nature, in effect, for the CCR5 receptor, in that individuals who lack gene expression of this receptor appear to have a full lifespan and no obvious immunological defects. The subset of individuals who are homozygous recessive for CCR5 receptor expression are over-represented among the occasionally identified highly exposed but non-infected individuals, relative to the general population, an observation that first led to the recognition of the key role of CCR5 for HIV entry 42 . Recent observations suggest the possibility that host deficiency of CCR5 expression, a protective state in terms of HIV pathogenesis, may increase the risk of encephalitis caused by West Nile virus 43 , and alter the risks for immune-mediated diseases such as multiple sclerosis 44 . Again, it would...

Disorders Of Laughter

In 1994, Shaibani, Sabbagh, and Doody proposed four criteria to distinguish pathological laughter and crying from normal laughter and crying. First, PLC is inappropriate to the situation since it occurs spontaneously or in response to nonspecific stimuli or inappropriate, arbitrary stimuli (e.g., one patient with a left cerellar hematoma showed pathological laughter following left hand tremor). Second, PLC is unmoti-vated that is, there is no relation between the affect and observed expression, nor is there relief or mood change afterwards. Third, PLC is involuntary that is, it has its own pattern and occurs against the patient's will. Neither the duration nor the content of PLC can be controlled, and patients do not gradually change from smiling to laughing but have a sudden, brief outburst without any warning. Fourth, PLC differs from emotional lability, which refers to an exaggerated emotional response to a normal stimulus. The latter characterizes patients with multiple sclerosis...

Multi Centre Trials in Other Conditions

BarKHoF et al. (1997) have considered the requirements for multi-centre trials in multiple sclerosis, identifying the need to establish observer variability over multiple centres, as well as improve quantification methods and compare the different techniques in a multi-centre longitudinal fashion in order to include variation caused by both scanner and segmentation techniques, in addition to biological activity. BarKHoF et al. (1993) report a database developed for recording serial brain MRI results suitable for multiple sclerosis multi-centre trials. Nyland et al. (1996) report on a randomised, double-blind, placebo controlled multi-centre study at eight centres in Norway to evaluate the efficacy and safety of 4.5 and 9.0 MIU recombinant human interferon alfa-2a (Roferon-A) given thrice weekly in patients with relapsing-remittent multiple sclerosis. The primary objective is to determine new disease activity analysed by monthly MRI with gadodiamide (Gd-DTPA-BMA, Omniscan).

Well Researched Cerebrospinal Fluid Markers in Patients With Probable Alzheimer Disease

5 of autopsied healthy normal individuals exceeded 3 ng ml. Levels in living CSF of 62 of possible or probable AD patients, 0 of normal controls, 2 of multiple sclerosis patients, and 16 of Parkison disease patients exceeded 3 ng ml Levels in living CSF of 89 of possible probable AD patients and 11 of normal controls exceeded 2 ng ml.

Human autoimmune and infectious diseases

Patients with multiple sclerosis (MS) have dramatically elevated levels of TGFp mRNA-expressing mononuclear cells in blood and CSF. MS patients also have elevated numbers of circulating MBP- and proteolipid protein (PLP)-reactive TGFp mRNA-expressing cells. Interestingly, patients with severe MS had fewer cells expressing TGF'P mRNA compared to patients with mild MS. In another recent study, patients with stable MS had higher levels of

Antigen Presentation and Effector Functions

Experimental autoimmune encephalomyelitis (EAE) is a widely used model of autoimmune CNS disease that mimics several aspects of human multiple sclerosis (MS). It is the prototype of a T cell-mediated CNS disorder and can be induced in susceptible animals by immunization with CNS myelin components or adoptive transfer of T helper cells primed against central myelin. Clinically, the disease is characterized by weight loss, paralysis, and ataxic gait developing at the end of the second week after immunization. Depending on the immunization protocol and the species used, animals recover spontaneously and disease subsides or animals develop a relapsing-remitting course. Histopathologically, EAE is characterized by massive T cell and macrophage infiltration in the CNS and variable degrees ofdemyelination. The interactions between T cells and macrophages are orchestrated by cytokines. In EAE, the balance between pro- and antiinflammatory cytokines most likely determines the clinical course....

TABLE 2022 Frequency of Presenting Signs and Symptoms in Hypoglycemia

Hypoglycemia has been misdiagnosed as stroke, transient ischemic attack, seizure disorder, traumatic head injury, brain tumor, narcolepsy, multiple sclerosis, psychosis, sympathomimetic drug ingestion, hysteria, altered sleep patterns and nightmares, and depression. -l8,9,1 and l1 Although uncommon, bradycardia has also been reported.12

Major Clinical Syndromes Of Aggression

Toxic-metabolic encephalopathies Vitamin B12 deficiency Alcohol, cocaine Multiple sclerosis Vascular dementia Delusional cognition Paranoid schizophrenia and sleep terrors, which arise out of non-REM sleep. Nocturnal seizures must also be excluded. The evaluation in suspected cases includes a thorough history of sleep complaints from patient and bed partner, neurological and psychiatric examination, overnight polysomnographic study, and MRI. REM sleep behavior disorder has been associated with a variety of neurological conditions, including Parkinsonism, dementia, stroke, multiple sclerosis, and alcohol withdrawal. However, more than 50 of cases are idiopathic. Pontine tegmental lesions, which might be expected from animal studies, are rare, possibly because pontine injury frequently produces devastating motor and arousal deficits that preclude expression of the disorder. Approximately 90 of patients exhibit sustained improvement when treated with clonazopam.

The Axonal Myelin Sheath

Myelin is not confined to axons. Somata and dendrites may be loosely wrapped in it. Myelin may be protective, assuring continued connectivity. In demyelinating diseases like multiple sclerosis, demyelinated axons conduct impulses, but less rapidly and efficiently. During remission, the improvement in conduction may be greater than the remyelination that has occurred.

Dementia Associated with Sensorimotor Signs

Inherited disorders of metabolism (e.g., metachromatic leukodystrophy, Kuf's disease) Normal pressure hydrocephalus Multiple sclerosis As noted on Table 7, there are numerous dementias that are associated with sensorimotor signs of which we will briefly mention HIV associated dementia, neurosyphilis, normal pressure hydrocephalus, multiple sclerosis, and extrapyramidal syndromes. These dementias tend to present with apathy, social withdrawal, blunted affect, diminished behavioral output, and compromised attention. For example, changes in mental state changes can be the presenting Patients with multiple sclerosis often suffer from cognitive, emotional, and behavioral problems that tend to add to their disability and problems functioning at home and work (122-124). Dementia has been reported in up to a third of patients with Parkinson's disease (125-128). Some patients have coexisting Alzheimer's pathology, which probably accounts for their decline in mental state functioning. Others...

Physiologic and pathologic significance of the MAC

The MAC plays an important pathophysiologic role in several autoimmune and inflammatory diseases. In some cases this may be due to its cytotoxic effect, as in several immune hematologic diseases. In many instances, however, the pathophysiologic participation of the MAC is more likely related to its ability to elicit cell activation when present in sublytic amounts. The MAC has been implicated in renal diseases such as acute poststreptococcal glomerulonephritis, membranous and membranoproliferative type III nephropathy and lupus nephritis, in neurological diseases such as multiple sclerosis, Guillain-Barr syndrome and myasthenia gravis, in rheumatoid arthritis and immune-complex vasculitis, and in the extension of myocardial infarction lesions and

Contribution to Disease

Luxol Multiple Sclerosis

Multiple Sclerosis Multiple sclerosis (MS) is a major demyelinating disease with pathological features similar to those of the experimental animal model, experimental allergic encephalomyelitis (EAE). Blood vessels in the CNS of MS patients characteristically have inflamed Figure 4 Demyelinated plaque occurring in the brain of a patient with multiple sclerosis. Tissue section staining with Luxol fast blue visualizes myelinated areas (dark) and regions devoid of myelin (light). Figure 4 Demyelinated plaque occurring in the brain of a patient with multiple sclerosis. Tissue section staining with Luxol fast blue visualizes myelinated areas (dark) and regions devoid of myelin (light).

Principles Of Neurotransplantation

The field of neural transplantation for the treatment of neurological diseases first became a potential therapeutic modality in 1979 when Bjorklund and Perlow showed that transplantation of dopamine containing neurons in rat striatum improved functional deficits induced by damage to the nigrostriatal pathway. Since that time, advances in neural transplantation have moved from the animal model to the human model with varying degrees of success. Animal models encompass a wide variety of disease states from degenerative diseases to trauma and stroke models. Tissue used for transplantation ranges from fetal tissue to tumor lines to stem cells. In some models, implants provide a source of neurotrophic factors. Successes in animal models have led to transplant trials in the human population. Patient trials include transplantation for Parkinson's disease, Huntington's disease, spinal cord injury, and stroke. As research in animal models progresses, transplant trials may be initiated for the...

Bdv And Human Disease

There have been no large, controlled prevalence studies. Furthermore, methods for diagnosis of human infection are not standardized thus, it is difficult to pursue meta-analysis. Most reports suggesting an association between BDV and human disease have focused on neuropsychiatric disorders, including unipolar depression, bipolar disorder, or schizophrenia however, BDV has also been linked to chronic fatigue syndrome, AIDS encephalopathy, multiple sclerosis, motor neuron disease, and brain tumors (glioblastoma multiforme) (Tables II and III). The improbably broad spectrum of candidate disorders has led some investigators to propose that infection is ubiquitous, and, that in some disorders, elevation of serum antibody titers or the presence of viral transcripts in peripheral blood mononuclear cells or neural tissues reflects generalized (AIDS) or localized (glioblastoma multiforme) immunosuppression.

Qualitative Features Of Neurocognitive Complications

HIV neurocognitive complications are often described as having subcortical features. This means that the pattern of impairment is somewhat reminiscent of that seen in neurological diseases that affect primarily the subcortical structures or white matter and possibly pathology involving frontostriatal circuits (e.g., Huntington's disease, Parkinson's disease, and multiple sclerosis). Persons with this pattern of neuropathology tend to have difficulties in psychomotor abilities, speed of information processing, initiation, divided

Neuroinflammatory disorders

Neuroinflammatory diseases share the same pathological finding of foci of degeneration in the myelin sheath of nervous tissue. Multiple sclerosis (MS) is the commonest neuroinflammatory, demyelinating disease, which affects the central nervous system. It is also the commonest cause of chronic neurodisa-bility in young adults, with a median age of onset of 31 years and prevalence in Britain of 80-100 100,000 population. It particularly affects the spinal cord, optic nerves and brainstem.

A LTP or Memory Formation Causes Changes in Gene Expression

Changes in gene expression can be measured in a number of ways. In fishing for the expression of genes that are unknown, two techniques have been used successfully subtractive hybridization and differential display. Subtractive hybridization permits a mathematical subtraction of gene expression in control tissue from expression in treated or perturbed tissue, allowing isolation of mRNA specifically from genes that have been upregulated or downregulated. Differential display involves amplification of both control and perturbed sequences and subsequent separation of the amplified products, which permits one to determine directly which sequences have been increased. However, with the completion of the Human Genome Project and with other entire mammalian genomes in reach, a technique called DNA microarray analysis has become increasingly important. In principle, DNA microarray techniques can measure expression of all known genes at one time, and it likely will become the method of choice...

Inflammatory Lesions 1 Infections

Multiple Sclerosis Multiple sclerosis is a demyelinating disorder affecting the CNS. The clinical associations reflect white matter damage upper motor neuron weakness and paralysis, incoordination, visual disturbances, and paraesthesia. The course is often acute onset followed by a progress of many years with alternating remissions and relapses. Less commonly, there are different variants, such as an acute severe disease that incurs a rapid progress to death, chronic progession without remis Multiple sclerosis is an autoimmune disease in which the patient's immune system reacts against the neuronal myelin sheath. In addition to demyelination, damage in the CNS occurs to the axons and an inflammatory filtrate can be detected. Although numerous aspects of the genetics, histopathology, and other immunological details have been the subject of recent and wide-ranging investigations, the precise pathophysiological course of the illness remains unclear.

The Cerebral Vasculature

When the blood-brain barrier is disrupted, edema fluid accumulates in the brain, leading to neurological impairments. Increased permeability of the blood-brain barrier plays a central role in many neu-ropathological conditions, including multiple sclerosis, AIDS, and childhood lead poisoning, and may also play a role in Alzheimer's disease (Claudio et al., 1995 Bu e et al., 1994). The blood-brain barrier is composed of three cellular components endothelial cells, pericytes, and astrocytes and one noncellular component the basement membrane. These components interact with each other to produce a highly selective and dynamic barrier system. In general, disruption of the blood-brain barrier causes perivascular or vasogenic edema, which is the accumulation of fluids from the blood around the blood vessels of the brain. This is one of the main features of multiple sclerosis. In multiple sclerosis, inflammatory cells, primarily T cells and macrophages, invade the brain by migrating through...

Neuropsychological Testing

The clinical neuropsychological evaluation of patients with possible toxic encephalopathy necessitates that the clinician perform a careful and thorough examination of each patient. Many areas of cognitive function must be assessed so that exposure-related effects can be detected and other possible diagnoses comprehensively evaluated and ruled in or out. Because there is overlap between the behavioral effects of exposure to certain neurotoxic chemicals and those associated with developmental disorders (e.g., learning disabilities, attention deficit disorder), psychiatric conditions (e.g., posttraumatic stress disorder, bipolar disorder), neurological diseases (e.g., multiple sclerosis, cerebrovascular disease, primary progressive dementia, parkinsonism), and the exposure to ethanol, medications, and illegal drugs, the test battery must allow for consideration of these alternative or contributing conditions. E. Conditions with overlapping pathologies can make differential diagnosis...

Clinical Presentation

Misdiagnosis of the persistent vegetative state is not uncommon but unfortunately may severely affect patient care. Some individuals initially described as having persistent vegetative state do not meet the strict diagnostic criteria of this syndrome. Patients have been found to be interactive with their environment, to possess alternative diagnoses such as multiple sclerosis, or to be in coma rather than in the persistent vegetative state.

Validation Studies of Dynamic Contrast Enhanced MRI

Oesophage Marteau Piqueur

The DCE-MRI approach is widely used to draw inferences into microvascular parameters such as microvascular permeability, blood volume, and tissue perfusion. Confirmed insight into the whereabouts, and amount of the tracer, at the tissue level would unquestionably help to determine the most accurate and precise way to model the signal changes in DCE-MRI. This can be accomplished by correlating DCE-MRI with quantitative transmission electron microscopy (TEM) methods. TEM can be used, in combination with energy dispersive X-ray spectrometry (EDXS) microanalysis to assess the subcellular content and location of heavy metals like gadolinium and iron (Elster 1989 LoPachin and SaubermanN 1990 Taherzadeh et al. 1998). This method analyses the characteristic X-ray patterns, produced from the heavy metal based MRI contrast agents when an electron beam passes through the tissue. Where the concentration is high enough elemental distribution maps can be produced (LoPachin and Saubermann 1990). A...

Routes of administration

For longer-term feeding, pharyngostomy and oesophagos-tomy are used by some surgeons. Surgically placed gastros-tomies are used for long-term administration of feed for patients with progressive deglutition disorders (motor neurone disease, multiple sclerosis). Stamm gastrotomy (Fig. 4.2) is simple to perform as a temporary procedure. The removal of the tube is rapidly followed by closure of the cutaneous orifice. The percutaneous endoscopically-placed gastrostomy (PEG) is now the technique of choice for long-term administration of EN. This technique has a lower morbidity and mortality, when compared with the conventional surgical placement. A needle catheter jejunostomy is shown in

Oxidative Stress Related Disorders

Oxidative stress is implicated in the inflammatory demy-elination that characterizes multiple sclerosis suggesting GST polymorphisms may be associated with disability. In 177 patients with disease duration over 10 years, GSTM3 AA (OR 2.4) and homozygosity for both GSTM1*0 and GSTP1*Ile105-encoding allele (OR 5.0) were linked with severe disability suggesting that long-term prognosis in MS is influenced by GST-mediated ability to remove toxic products of oxidative stress. 1 Exposure to ultraviolet radiation also results in local oxidative stress in skin. Response to such exposure, examined as minimal erythema dose, has been shown to be mediated by GSTM1 and GSTT1 genotype in a gene dosage-dependent manner. 19 Furthermore, nonmela-noma skin cancer has also been linked to these poly-

Clinical Description of Infection

These viruses are ubiquitous and frequently reactivate. Proof that viral replication is causal in specific disease associations is usually lacking. The greatest attention has focused on links between HHV-6A and multiple sclerosis and HHV-7 and the skin rash pityriasis rosea. Links between HHV-6 HHV-7 and chronic fatigue syndrome have not been substantiated by molecular techniques.

Diagnostic Assessment

Medical conditions which may present with manic symptoms include infectious diseases (encephalitis, influenza, syphilis, AIDS), endocrine disorders (hyperthyroidism), tumours, and neurological conditions (temporal lobe epilepsy, multiple sclerosis, Wilson's disease, closed or open head injury). Manic symptoms may be induced by medications (steroids, isoniazid, sympathomimetics) and alcohol or drug abuse.

Epidemiology and Diagnosis

In the history it is important, as well as asking about LUTS, to exclude any other co-morbidities that could be contributing to the presentation. It is important to exclude neurological disorders, including cerebrovas-cular events, multiple sclerosis (MS), spinal cord injury (SCI), pelvic or perineal trauma, Parkinson's disease, multisystem atrophy (MSA), and motor neuron disease (MND), and consider if they are taking any drugs that could contribute to dysfunctional voiding (anticholin-ergics, antidepressants, anesthetic agents, analgesics). Also, it is important to assess the patient's general medical state to ensure that they are not going to come to any harm as a result of any therapy instigated.

Cerebrospinal Fluid Tests for Alzheimer Disease

NYMOX has developed a quantitative test for measuring levels of a specific type of neuronal thread protein (AD7c-NTP) in small samples of CSF (70-72). This protein is overexpressed in brain neurons in AD. The promotional material of NYMOX indicates that in 80-90 of autopsy-verified cases of AD, the level of this protein exceeds a designated cut-off level, while less than 5 of control values exceed this level. This test is being advertised as the first test proven to help physicians be certain in the diagnosis of Alzheimer's disease . . . now you can rule it out. Because interpathologist agreement for the diagnosis of AD by brain autopsy is about 85 , it has been suggested that the CSF test might be used as a gold standard against which other antemortem tests for AD are compared instead of brain autopsy. The 1992 publication had some important limitations. Around 70 of clinical patients with probable AD were reported to have AD7c-NTP levels > 3 ng mL in contrast to less than 5 of...

Glial Fibrillary Acidic Protein

GFAP is an intermediate filament protein expressed in astroglia. It was first isolated from multiple sclerosis brain, in which astrocytes are very reactive. Intermediate filaments constitute major components of the cytoskeleton of eukaryotic cells as 10-nm filaments. On the basis of differences in size and amino acid sequences, GFAP together with vimentin and desmin are classified as type III intermediate filament proteins. They are composed of three distinct regions an amino-

Microarray Analysis of Human Brain Disorders

Postmortem microarray research of neurological disorders has been very productive over the last several years. In particular, transcriptome profiling of Rett's syndrome, Alzheimer's disease (AD), and multiple sclerosis (MS) has been at the forefront of these analyses, and the results are providing a fundamentally new view of these disorders. Analysis of the frontal cortex in subjects with Rett's syndrome revealed that mutation of transcriptional repressor methyl-CpG binding protein-2 (MECP-2) leads to alterations in the mRNA levels NMDA-NR1, MAP-2, and synaptic vesicle proteins (Johnston et al, 2001), as well as increased expression of glial markers (Colantuoni et al., 2001).

The cerebral white matter constitutes approximately onehalf

Subcortical gray matter regions within and between the hemispheres, and it enables more efficient neuronal transmission and cerebral function. Disorders of the cerebral white matter comprise a diverse group of neuropathologic conditions, of which multiple sclerosis is the best known. Neurologic dysfunction is well-known to be associated with these disorders, and neurobehavioral syndromes including dementia are also being increasingly recognized. Recognition of these clinical phenomena represents an opportunity to improve the care of individuals with these disorders and to expand our understanding of the human brain.

Techniques Used in Humans 1 Microstructure

Visualization of white mater bundles in humans is important for issues of both clinical and basic science. In clinical neurology, there are many conditions, such as stroke, multiple sclerosis, amyotrophic lateral sclerosis, and traumatic head injury, that lead to pathological alterations in white matter tracts. Imaging techniques allow improved in vivo diagnosis and analysis of these conditions. These techniques also offer immense promise as a probe of normal connectivity in the human brain.

Differential Diagnosis

Careful history taking and physical examination should be used to rule out neurologic disease. A high index of suspicion should be maintained for physical disorders that have a vague onset, such as systemic lupus erythematosus, multiple sclerosis, polymyositis, Lyme disease, and drug toxicity or poisoning. Schizophrenia and depression may have associated conversion disorders. In somatization disorders, the symptoms are more chronic and involve multiple organ systems. With hypochondriasis, patients are usually without loss of function and display the conviction that some terrible undiscovered illness is present. Hypochondriacal patients will be overly concerned with symptoms. In cases of factitious symptoms, usually associated with malingering, patients will consciously complain about symptoms to

Human Neurological Diseases Studied by Microarray Technology

Multiple Sclerosis The complexity and ad hoc methods of the design and analysis in this study results in uncertainties about interpreting the conclusions. Rather than use an average-fold ratio across a class, the authors use individual experiment's fold ratios subject to additional constraints. There is no statement about reproducibil-ity studies performed by the authors and the very small numbers and particular definition of significance make it difficult to accept the results confidently. In addition, the title of this report is highly inappropriate (''Expression Profiling Identifies Responder and Non-responder Phenotypes to Interferon- in Multiple Sclerosis''). The claim made is that of class prediction that measuring an expression profile allows one to identify whether a patient is a responder or not. Such a claim is difficult to understand given that no class prediction methods (Table I) were used in this study. It is easy to make thousands of measurements and find one or a...

Considering environmental factors

Endometriosis is related to environmental contamination. Dioxin, one of the first pollutants scientists studied, is an example (see the sidebar Understanding dioxin exposure earlier in this chapter) of an environmental effect on endometriosis. Likewise, scientists can link pollutants to multiple sclerosis, lupus, thyroid disease, chronic fatigue syndrome, fibromyalgia, and even cancer.

Pathology

Oligodendrocytes are compromised in many neurological diseases, including demyelinating diseases (e.g., multiple sclerosis), metabolic diseases (e.g., Pelizaeus-Merzbacher's disease), infectious diseases (e.g., progressive multifocal leukoencephalopathy), neurodegenerative diseases (e.g., Alzheimer's disease), and tumors (e.g., oligodendrogliomas). Under pathological conditions oligodendrocytes assume the various functions described above, the nature of the function partly dependent on the particular cell type. However, this cell type is mainly activated under conditions of myelin degeneration, and their main function is remyelination. Destruction of oli-godendrocytes induces unchecked demyelination, with disastrous consequences for brain function.

Health History

Nonetheless, these early successes were achieved at very high costs. Johns Hopkins Oncology Center, for example, acquired their first computer system in 1976 for a quarter million dollars its processing power was only a fraction of today's desktop computers. Other successful early patient record systems include the Computer Stored Ambulatory Record System (COSTAR), the Regenstrief Medical Record System (RMRS) and The Medical Record (TMR). COSTAR, a patient record system developed at Massachusetts General Hospital by Octo Barnett in the 1960s, was later extended to record patient data relating to different types of ailments (for example, multiple sclerosis MS-COSTAR ) and is used even today in several teaching hospitals and research universities across the globe. RMRS was a physician-designed integrated inpatient and outpatient information system implemented in 1972, and TMR is an evolving medical record system that was developed in the mid-1970s at Duke University Medical Center....

Cytokines

A modern study of the host response to endotoxin (or any pyrogen) quickly becomes a study of cytokines. Once an exogenous agent (or event) has triggered the inflammatory response, the host's response is believed to no longer depend upon the agent activating the cascade but rather becomes self perpetuating. The symptoms and progressive effects may continue on the given course, and even intensify after the agent has been cleared from the system and or after the event (burn, wound, etc.) has passed. The study of cytokines and their effects has been a field of explosive and fertile growth during the biotechnology revolution. Many genes encoding these substances have been cloned and expressed, and several have been commercialized as treatments for a variety of diseases including viral infections, multiple sclerosis, and certain cancers.

Radiation Therapy

Prophylactic brain irradiation is widely used in patients with lung cancer and acute leukemia. Cognitive domains impaired as a result of radiation therapy include information processing speed, executive functions, memory, sustained attention, and motor coordination. Anatomically, periventricular white matter hyperintensities are observed on neuroimaging. The pattern of deficits is consistent with those seen in other subcortical diseases of white matter such as multiple sclerosis. Children are particularly vulnerable to radiation injury to the brain. Even relatively low-dose cranial irradiation can cause mild declines in intelligence in older children, with more severe impairments in memory, acquisition of academic skills, and attentional skills in children treated before age 5. In both adults and children there is conflicting evidence whether concomitant chemotherapy is synergistically toxic. Finally, many patients with head and neck cancers, such as paranasal sinus tumors and...

Neurologic Diseases

The elderly comprise the largest percentage of cancer patients. Patients in older age groups are not only at increased risk to develop cancer but also more vulnerable to age-related neurocognitive disorders unrelated to but coexisting with cancer, such as cerebrovascular disease and dementia of the Alzheimer's type. Cancer patients may also have a preexisting history of traumatic brain injury, developmental disorder, multiple sclerosis, and other conditions or diseases that affect cognitive functioning. These patients may be more vulnerable to develop neurotoxic side effects from cancer and cancer treatment and need to be monitored closely.

Neuroimaging

The study of cerebral white matter has been dramatically facilitated in the past three decades by the development of powerful neuroimaging techniques. Computerized tomography (CT) scanning became available in the 1970s, and for the first time a noninvasive image of the brain in vivo became easily obtainable. Magnetic resonance imaging (MRI) was introduced in the 1980s and offered much improved visualization of brain structures, particularly white matter. MRI has been a most significant advance in the understanding of white matter disorders, revolutionizing the diagnosis of multiple sclerosis (MS) and rapidly expanding the list of disorders with white matter pathology that were previously difficult to detect. Another development in the field of MRI is the advent

Autonomy of Actions

Specific situations in which superficial preoccupation with the issues of patient autonomy and death with dignity could have led to inappropriate clinical and ethical decisions (p. 407). In one of the cases, a patient with multiple sclerosis appeared to autonomously refuse further lifesaving treatment following a suicide attempt. However, psychiatric evaluation showed that the patient had become depressed and withdrawn at the time his wife and sons began spending time with his mother-in-law who had been diagnosed with inoperable cancer.

Demyelination

Important challenges for the future are the derivation of functional oligodendrocytes from hES cells and the demonstration of functional benefits in vivo, including strategies to obtain remyelination over more extended CNS regions. In clinical terms, the transplantation of ES-derived oligodendro-cytes into models of multiple sclerosis would be of particular interest. However, a successful strategy will require sophisticated strategies to overcome host-mediated factors that prevent oligodendrocytes maturation as well as strategies that address the autoimmune nature of the disease.

Applications

A principal clinical application of evoked responses has been for assessment of the patency of sensory information processing pathways. Measurements of the ABR and early VEP have been used as objective diagnostics for the integrity and proper development of the auditory and visual pathways in infancy and childhood. The latency of the VEP has been used for the assessment of multiple sclerosis. Demyelination associated with this progressive degenerative disorder causes decreases in conduction velocity apparent as increases in the latency of cortical response components. Endogenous response components such as the P300 have been used as a generic probe of psychological and cognitive processes in disorders ranging from schizophrenia to Alzheimer's to alcoholism. In many cases the link between the diagnostic measure and the underlying pathology is tenuous, but statistical differences between normal and affected individuals can be observed.

Autoimmunity

The well-documented examples of drug-induced autoimmune-like syndromes have led to studies to determine whether certain agents contribute to the incidence of autoimmune diseases. Some of the chemical and therapeutic agents suggested to be associated with autoimmune diseases or autoimmune phenomenon (i.e. increased levels of autoantibodies), in experimental animals or humans are listed in Table 1 and include several heavy metals, pharmaceuticals, organic solvents and foods. As a number of factors participate in the development of autoimmune disease and it presents both diverse clinical symptomology and organ specificity, appropriate animal models have been difficult to develop. One method that has received attention is the popliteal lymph node assay (PLNA) which measures proliferative activity in the draining lymph nodes. Although this assay appears to detect low molecular weight compounds with immunomodulatory potential, it does not necessarily discriminate those that influence...

Figure

Extrapyramidal syndromes such as Wilson's disease, Parkinson's disease, progressive supranuclear palsy, cor-ticobasal ganglionic degeneration, and multiple system atrophy may be associated with dystonia. Parkinson's disease may present with symptoms of lower limb dystonia. Patients with progressive supranuclear palsy often present with dystonic muscle contraction of the axial muscles, and some patients with corticobasal ganglionic degeneration will exhibit profound limb dystonia in addition to, and sometimes masking, symptoms of alien-limb phenomenon. Tonic spasms of multiple sclerosis are typically transient attacks of hemidystonia of the limbs. Reported secondary causes of dystonia include exposure to dopamine receptor-blocking drugs (tardive dystonia) hypoxic encephalopathy, head trauma, encephalitis, human immunodeficiency virus (HIV) and other infections, peripheral or segmental nerve injury, reflex sympathetic dystrophy, inherited disorders (e.g., Wilson's disease), metabolic...

Voiding symptoms

LUTS are a feature in women with urethral stenosis or obstruction of the urethra by a gravid uterus or severe genital organ prolapse. Failure of the normal sphincter mechanisms to relax and open during voiding will lead to voiding symptoms. This is seen after spinal trauma and in some patients with multiple sclerosis.

Basic Principles

It is not the intention of the present chapter to present clinical neuropathology in all of its complexity. Instead the focus will be mainly on sudden and unexpected death attributable to intracranial disorders and or functional disturbances of the CNS in adults. Similar naturally occurring processes in children are discussed elsewhere (pp. 451 ff). Cerebral diseases coincidentally associated with sudden, unexpected death or resulting from initially survived external violence such as impact or intoxication are additionally treated here. Because the neuropathologist is often confronted with such disorders in connection with forensic questions, they are relevant to the topic of the present volume. Diseases of the latter type can lead to death due to generalized cerebral or extracerebral processes or events. Typical chronic or acute neurological disease processes that do not lead directly to death, i.e. multiple sclerosis will be shortly discussed, but the usual spectrum of neurological...

Treatment

Prognostic Features of Multiple Sclerosis Favorable Less favorable Genetic engineering has led to the manufacture of compounds such as interferon-b (IFN-b), which is where produced by Escherichia coli or mammalian ovarian cells after gene insertion. Copaxone (glatir-amer acetate) is a synthetic compound made of four amino acids. These agents allow for selective immunomodulation and thus lower toxicity. There is conclusive evidence from large-scale trials that these agents are partially effective in the treatment of MS. IFN-b-1b (Betaseron) was the first of these agents to be assessed. The drug was shown to effectively decrease the risk of exacerbation of MS and had the effect of slowing accumulation of new lesions on MRI. Although the drug did not show an effect on slowing progression of disease, as measured by the EDSS, the effect on MRI led many to believe that the long-term outcome of a patient treated with this will be better than the expected natural history. IFN-b-1a (Avonex)...

TlWeighted Methods

Contrast agents used with MRI have predominantly been based on gadolinium chelates, providing a positive contrast on Tl-weighted images. Their initial application was to demonstrate areas of blood-brain barrier breakdown, as a method of identifying and classifying CNS lesions such as those from multiple sclerosis, or from cancer. More recently in cancer their use has extended to the evaluation of other solid tumours, aiding discrimination of active disease from fibrosis, necrosis and normal tissues. They are used in other applications to identify perfusion defects, and to increase the sensitivity of MR angiog-raphy. In tumour studies, in addition to morphological assessment of the enhanced region, there has been interest in evaluating the dynamics of contrast uptake and wash out, which can be related to physiological parameters by the use of appropriate physiological models.

Cytokine regulation

The CD4 molecule functions as a coreceptor for T cell receptor-antigen interactions and contributes to the intracellular signaling pathways required for CD4' T cell activation. CD4+ cells are involved in the pathogenesis of several autoimmune diseases, e.g. multiple sclerosis, and participate in transplantation reactions. Over the last few years, several approaches have been developed to inhibit the responses of CD4 T cells, including the use of mAbs and peptides which compete for the presentation of antigens, yet these may have broad effects on all CD4h T cells. Recently, synthetic peptides that mimic structural features of the CD4 molecule itself have been designed to block the functional role of CD4 during antigen-specific T cell activation. It is thought that this approach can achieve inhibition of the CD4 T cells that participate in autoimmunity or transplantation reactions, without impairing the ability of other T cells from later responding to other antigenic challenges.

Introduction

Disease-specific genes in human tissues have been made for such neurological conditions as multiple sclerosis (Mycko etal., 2003), Alzheimer's disease (Colangelo et al., 2002 Ginsberg et al., 2000 Marvanova et al., 2003), psychiatric disorders (Bunney et al., 2003 Middleton et al., 2002 Mirnics et al., 2000 Pongrac et al., 2002), and epilepsy (Elliott et al., 2003).

White Matter

Collections of axons ensheathed with myelin that are most often called tracts, but that may also be termed fasciculi, bundles, lemnisci, funiculi, and peduncles. Traveling extensively throughout the brain to link widely dispersed gray matter areas, these groups of fibers integrate cortical and subcortical regions into functionally unified neural networks. These networks subserve the many unique functions of the brain, from basic sensory and motor activities to complex cognition and emotion. By virtue of the dramatic increase in axonal conduction velocity that is afforded by myelin, rapid and efficient transfer of information across white matter tracts occurs, which enables the highest functions in the cerebral hemispheres. The many neurologic and neurobehavioral deficits sustained by individuals with the white matter disease multiple sclerosis (MS) testify to the importance of white matter in brain function.

Function

Schwann cells have been implicated in the repair of axons after injury. One of the major differences between peripheral and central axons is that the peripheral nerves will regenerate to a large degree whereas central axons seem unable to do so. This accounts for the devastating injury seen in patients whose central axons have been damaged, e.g., spinal cord trauma and multiple sclerosis. In the peripheral nervous system, cut axons can sprout and these sprouts elongate and reconnect with the correct targets. In the CNS, axons sprout but cannot advance to their original targets thus, regeneration fails. In the peripheral nervous system the neurotrophins NGF, NT3, and BDNF show beneficial effects on the survival of axons, and these are also released from Schwann cells. More recent studies have indicated that peripheral nerves can be used in the regeneration of central axons. In the spinal cord, injection of Schwann cells into the site of injury is a promising strategy to aid...

The Brain

There is recent evidence that low maternal vitamin D can adversely affect brain development in the fetus.3840 In newborn offspring of vitamin D deplete rat mothers (versus controls), the cortex had a higher length width ratio and was proportionally thinner, and lateral ventricle volume was greater.40 Throughout the brain there was more cell proliferation. The proportion of mitotic cells was increased while nerve growth factor content was reduced.39 Some of these brain features altered in vitamin D deficiency are similar to those reported in patients with schizophrenia. It has been hypothesized that low maternal vitamin D may contribute to increased susceptibility to neurological disorders, including schizophrenia and multiple sclerosis in the offspring.414 In a recent study using data from the Northern Finland 1966 Birth Cohort, males given at least 2000IU of vitamin D per day in the first year of life had reduced risk of schizophrenia (Risk ratio 0.23, 95 CI 0.06-0.95) compared with...

Bruno Antonsson

Apoptosis Mitochondrial Pathway Swelling

Multicellular organisms are dependent on the removal of damaged or unwanted cells both during their development and in the adult life. This is ensured by apoptosis or programmed cell death. Apoptosis is an active energy (ATP) requiring process where cells are eliminated in an ordered manner. A large variety of different stimuli, both extracellular signals and signals generated from inside the cell itself can initiate the apoptosis signaling cascades. Two intracellular apoptosis signaling pathways have been identified, the death-receptor pathway and the mitochondrial pathway. Apoptosis is accompanied by characteristic morphological and biochemical changes, such as chromatin condensation, DNA degradation, nuclear fragmentation, exposure of phosphatidylserine on the outside of the plasma membrane, and finally cellular fragmentation into apoptotic bodies. Although, apoptosis is an essential process, it is also involved in a wide range of pathologies. Increased apoptosis has been...

Immunotherapy

Other cytokines have also been used in clinical trials against cancer, and the cognitive impairments tend to be similar to those seen with IFN-a. IL-2 and TNF can cause memory deficits, difficulties with motivation and flexible thinking, motor dyscoordina-tion, depression, and anorexia. Visuoperceptual and language functions tend not to be affected. TNF exhibits dose-dependent toxicity such as decreased attentional abilities, verbal memory deficits, motor coordination impairments, and frontal lobe executive dysfunction. Headache, anorexia, stroke-like events (e.g., transient amnesia), and demyelination in the brain are also adverse effects of TNF. IL-1 and its receptors are found in many areas of the brain, particularly the hippocampus. IL-1 suppresses the influx of calcium into the hippocampus neurons, which may explain the preponderance of memory impairments in patients with IL-1-associated toxicity. The neurotoxic effects of IL-2 appear to be dose related and occur in nearly all...

Excitotoxicity

A slower, subtler form of excitotoxicity is implicated in a variety of chronic and slowly progressing neurodegenerative disorders as well as in the penumbra of stroke damage. In disorders such as AD, Huntington's disease, Parkinson's disease, multiple sclerosis, HIV-associated dementia, ALS, and glaucoma, it is hypothesized that chronic exposure to moderately elevated glutamate concentrations or glutamate receptor hyperactivity for longer periods of time than occur during normal neurotransmission trigger cellular processes in neurons that eventually lead to

Abducens Nerve

Is characterized by weakness in adduction of the eye on the side ipsilateral to the lesion during attempted conjugate eye movements toward the opposite side accompanied by nystagmus in the contralateral, abducting eye. Bilateral internuclear ophthalmoplegia can occur due to multiple sclerosis.

Physiology

Schwann cells have been implicated in Charcot-Marie-Tooth disease, a common inherited heterogeneous group of peripheral neuropathies. This disease is usually inherited as an autosomal dominant disorder, although recessively inherited forms do occur less commonly. Charcot-Marie-Tooth (CMT) disease is associated with severe demyelination of peripheral nerves, which results in greatly slowed conduction velocities in the nerves and results in muscle dysfunction and atrophy. It is a slowly progressive disease, and patients may ultimately become unable to walk. The most frequent form of the disease CMT1, designated CMT1A, is caused by abnormalities of one of several genes expressed in Schwann cells. The majority of cases have been shown to be associated with duplication in the p11-p12 region of chromosome 17, which contains the peripheral myelin protein 22 (PMP22) gene, which encodes one of the major PNS myelination proteins. A less common form of CMT1 (CMT1B) is caused by mutation in the...

Incontinence

Overflow incontinence is a result of urinary retention from a hypotonic detrusor muscle. This is seen in the setting of neuropathy secondary to diabetes, spinal cord injuries, outflow obstruction, postoperatively, or lower motor neuron diseases (i.e., multiple sclerosis). Symptoms include postvoid bladder fullness (the feeling of never having an empty bladder), small quantities on micturition, and leaking. Diagnosis is made through complete history and physical examination with emphasis on the neurologic examination and determination of postvoid residual volume. Therapy is directed at treating the underlying cause and teaching intermittent self-catheterization.

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