Update of autoantibodies in neurologic disease.

Many neurologic disorders recently have been discovered to have an autoimmune basis with autoantibodies that are responsible for neurologic symptoms and progression of the disease. Diagnosis and treatment of these disorders are facilitated by detection and monitoring of several autoantibodies. Some tumors express protein antigens shared by neurons, and an antitumor immune response leads to autoimmune antineuronal reactions exemplified by "paraneoplastic cerebellar degeneration." Other antibodies react with gangliosides present in many locations of the nervous system, leading to motor neuron damage and polyneuropathy. Phospholipid antibodies indirectly cause neurologic syndrome largely through thrombosis of cerebral vessels; other autoantibodies also have associations with specific neurologic symptoms.     

Misdiagnosis of chronic pain as hysteria and malingering

Chronic soft tissue pain disorders are not well understood from a pathophysiologic standpoint. Psychologic difficulties are common, clinical signs incompatible with conventional understanding of the nervous system are often present, and these disorders usually fail to respond to medical intervention.When this constellation of factors is combined with unresolved litigation-compensation issues, it is not surprising that chronic pain disorders are often misdiagnosed as hysteria or malingering. Unfortunately, these diagnoses may have significant negative consequences that are not often appreciated and may compromise treatment.     

Lyme disease: neurologic manifestations

Lyme disease is a multisystem infectious, inflammatory, and immune-related disorder that follows the bit of an Ixodes dammini tick infected with Borrelia burgdorferi. Subsequent manifestations are protean. This is particularly true concerning the nervous system. It is estimated that 15% of patients with Lyme disease have neurologic complications. It is very possible that nervous system manifestations of Lyme disease are even more common, and these can occur from weeks to many years following the primary infection and can be quite devastating. A high index of suspicion is necessary in diagnosing Lyme-related disorders, because the majority of patients will not recall a tick bite or characteristic rash, and because the subsequent neurologic manifestations are not unlike those seen with many other diseases. With this awareness and appropriate laboratory testing, a presumptive diagnosis can usually be made without significant difficulty. When the nervous system has been affected by Lyme disease, aggressive antibiotic treatment is usually necessary, often using IV preparations. Usually, there will be significant improvement following the use of antibiotics, but there are some patients who will continue to have persistent, probably irreversible, nervous system abnormalities. This is often the case in patients who have had symptoms for long periods of time or who have had multiple recurrences.     

Evaluation and management of the dizzy patient.

Evaluation and management of the dizzy patient remains frustrating to both the patient and physician. Numerous disorders may induce dizziness; these include not only inner ear disoders but also various central nervous system, ocular, and general systemic disturbances. Since dizziness has many variations, the subtle nuances the symptom may manifest must be explored throughly. Similarly, a consistent approach to the patient's physical and larboratory examination must be taken to understand the pathophysiology of the dizziness. This includes comprehensive auditory and vestibular evaluation, complete neurologic and ophthalmologic examination, and laboratory evaluation for latent or manifest systemic disease. The management of dizziness and vertigo is largely symptomatic. Certain exceptions exist where specific medical and surgical approaches may be beneficial, but the limitations of such treatment must be appreciated.     

Immunotherapies in neurologic disorders

Therapy for autoimmune demyelinating disorders has evolved rapidly over the past 10 years to include traditional immunosuppressants as well as novel biologicals. Antibody-mediated neuromuscular disorders are treated with therapies that acutely modulate pathogenic antibodies or chronically inhibit the humoral immune response. In other inflammatory autoimmune disorders of the peripheral and central nervous system, corticosteroids, often combined with conventional immunosuppression, and immunomodulatory treatments are used. Because autoimmune neurologic disorders are so diverse, evidence from randomized controlled trials is limited for most of the immunotherapies used in neurology. This review provides an overview of the immunotherapies currently used for neurologic disorders.     

Efficacy and Tolerability of Intravenous Immunoglobulin and Subcutaneous Immunoglobulin in Neurologic Diseases

PurposeIV immunoglobulin (Ig) therapy has been widely used for the treatment of neurologic disorders, autoimmune diseases, immunodeficiency-related diseases, blood system diseases, and cancers. In this review, we summarize the efficacy and tolerability of IVIg and SCIg therapy in neurologic diseases.MethodsWe summarized and analyzed the efficacy and tolerability of IVIg and SCIg in neurologic diseases, by analyzing the literature pertaining to the use of IVIg and SCIg to treat nervous system diseases.FindingsIn clinical neurology practice, IVIg has been shown to be useful for the treatment of new-onset or recurrent immune diseases and for long-term maintenance treatment of chronic diseases. Moreover, IVIg may have applications in the management of intractable autoimmune epilepsy, paraneoplastic syndrome, autoimmune encephalitis, and neuromyelitis optica. SCIg is emerging as an alternative to IVIg treatment. Although SCIg has a composition similar to that of IVIg, the applications of this therapy are different. Notably, the bioavailability of SCIg is lower than that of IVIg, but the homeostasis level is more stable. Current studies have shown that these 2 therapies have pharmacodynamic equivalence.ImplicationsIn this review, we explored the efficacy of IVIg in the treatment of various neurologic disorders. IVIg administration still faces many challenges. Thus, it will be necessary to standardize the use of IVIg in the clinical setting. SCIg administration is a novel and feasible treatment option for neurologic and immune-related diseases, such as chronic inflammatory demyelinating polyradiculoneuropathy and idiopathic inflammatory myopathies. As our understanding of the mechanisms of action of IVIg improve, potential next-generation biologics can being developed.     

Bone marrow transplantation prolongs life span and ameliorates neurologic manifestations in Sandhoff disease mice.

The GM2 gangliosidoses are a group of severe, neurodegenerative conditions that include Tay-Sachs disease, Sandhoff disease, and the GM2 activator deficiency. Bone marrow transplantation (BMT) was examined as a potential treatment for these disorders using a Sandhoff disease mouse model. BMT extended the life span of these mice from approximately 4.5 mo to up to 8 mo and slowed their neurologic deterioration. BMT also corrected biochemical deficiencies in somatic tissues as indicated by decreased excretion of urinary oligosaccharides, and lower glycolipid storage and increased levels of beta-hexosaminidase activity in visceral organs. Even with neurologic improvement, neither clear reduction of brain glycolipid storage nor improvement in neuronal pathology could be detected, suggesting a complex pathogenic mechanism. Histological analysis revealed beta-hexosaminidase-positive cells in the central nervous system and visceral organs with a concomitant reduction of colloidal iron-positive macrophages. These results may be important for the design of treatment approaches for the GM2 gangliosidoses.     

Human immunodeficiency virus and the nervous system

In conclusion, there are a number of neurological manifestations of HIV infection, affecting both the central and peripheral nervous systems. Involvement of the CNS may occur very early in the course of infection and manifest itself as an acute aseptic meningitis. HIV encephalopathy is currently the most commonly diagnosed neurologic disorder associated with HIV and may in fact occur as a direct result of HIV infection in the brain. In years to come, HIV encephalopathy may assume epidemic proportions. Thus, nurses and other health care workers will have to be well versed in the major symptoms as well as the subtleties associated with this disease. Any drugs effective in treating these neurologic disorders must be capable of crossing the blood-brain barrier. AZT is currently being evaluated in the treatment of HIV encephalopathy. Only carefully designed prospective studies will define the natural history of neurologic disorders seen with HIV infection, as well as drugs effective in their treatment.     

Medical marijuana: emerging applications for the management of neurologic disorders

Marijuana contains over 60 different types of cannabinoids, which are its medicinally active ingredients. Cannabinoids have the capacity for neuromodulation--through direct, receptor-based mechanisms--at many levels within the nervous system, providing therapeutic properties that may be applicable to the treatment of neurologic disorders. These include antioxidation, neuroprotection, analgesia, anti-inflammation, immunomodulation, modulation of glial cells, and tumor growth regulation. This article reviews the current and emerging research on the physiologic mechanisms of endogenous and exogenous cannabinoids and their applications in the management of neurologic disease.     

Immunomodulation by statins: inhibition of cholesterol vs. isoprenoid biosynthesis.

Due to their ability to inhibit the synthesis of cholesterol, statins are widely used in medical practice and are the principal therapy for hypercholesterolemia. In addition, various findings suggest that statins also exert anti-inflammatory properties and may so play a role in modulating the immune system. Because of these properties, statins could provide a potential treatment for various chronic inflammatory diseases, including neuroinflammatory disorders such as multiple sclerosis. Here, we will review the effect of statins on the expression and function of a variety of immune relevant molecules and the underlying mechanisms that contribute to the immunomodulatory properties of statins. In this discussion we will also evaluate the effects of statins on central nervous system cells to emphasize the potential of these agents in the treatment of neuroinflammatory disorders.     

Multiple sclerosis: update in diagnosis and review of prognostic factors

The cornerstone of the diagnosis of multiple sclerosis is the neurologic history and examination. Support for the diagnosis as well as aid in the exclusion of other disorders can be obtained from other investigations. Analysis of cerebrospinal fluid can provide evidence of a central nervous system inflammatory process; evoked potential studies can provide evidence of subclinical multifocal involvement of the central nervous system. Magnetic resonance imaging can reveal dissemination of white matter lesions and help in the exclusion of other neurologic disorders. These tests have been incorporated into the modern diagnostic criteria for multiple sclerosis. The natural history of multiple sclerosis is variable; accordingly, early in the clinical course of the disorder, predicting the prognosis for a specific patient is usually difficult. Nevertheless, some features have limited predictive value.     

Differentiating organic from functional psychosis.

Psychosis is not pathognomonic of psychiatric illness. It is simply a nonspecific cluster of signs and symptoms that may occur in a broad array of medical, neurologic and surgical disorders or as a consequence of pharmacologic treatment, substance abuse or the withdrawal of drugs and alcohol. Psychoses are classified as organic or functional mental disorders. Organic disorders with psychosis are caused by structural defects or physiologic dysfunction of the brain. The causes of functional disorders have not yet been identified. Psychoses are also categorized as effective or nonaffective in character. Affective and nonaffective psychoses may be associated with either organic or functional disorders.     

Elevation of carcinoembryonic antigen in cerebrospinal fluid among patients with meningeal carcinomatosis

The concentration of carcinoembryonic antigen (CEA) in cerebrospinal fluid (CSF) was determined by using an enzyme immunoassay for 204 patients with various nonneoplastic neurologic disorders, 8 patients with systemic infectious diseases, 19 patients with systemic neoplastic diseases without involvement of the nervous system, and 35 patients with neoplastic neurologic disorders. The highest CEA level in CSF among patients without neoplastic neurologic disorders was 0.6 ng/ml. Of 35 patients with neoplastic neurologic disorders, 10 had CEA levels in CSF that exceeded 0.6 ng/ml, the highest level being 70.5 ng/ml. All 10 patients had carcinomas. Among 14 patients with neoplastic meningitis, 5 of 8 patients with meningeal carcinomatosis had elevated CEA concentrations. Although the efficacy of the assay for CEA in CSF must be compared with that of other laboratory tests such as cytologic examination and the assay for beta-glucuronidase--and any potentially false-positive results should be ruled out by determination of the serum CEA level--the CEA concentration in CSF can be used as an adjunctive diagnostic procedure for detection of meningeal carcinomatosis.     

Le syndrome compartimental abdominal

A rapid and uncontrolled increase in the volume of intra-abdominal organs can induce an intra-abdominal hypertension which leads to organ dysfunctions: renal, gastro-intestinal, hemodynamic, respiratory and neurologic. The association of these organ dysfunctions to an increased abdominal pressure level over 15–20 mmHg has been known as the abdominal compartment syndrome. Along with surgical and traumatic patients, the syndrome has been described in medical critically ill patients. Suggestive systemic symptoms are mainly decreased cardiac output with metabolic acidosis, oliguria, hypoxia and increased airway pulmonary pressure. Finally, it can result in multiple organ failure. The confirmation of abdominal compartment syndrome is simply performed by the measurement of bladder pressure. The syndrome might lead to an increased mortality rate in critically ill patients. The specific treatment remains not determined: early surgical decompression might improve the outcome but different medical treatments (neuromuscular blockade, gastric suctioning, hemofiltration) remain to be evaluated. A greater awareness of abdominal compartment syndrome might improve the management of multiple organ failure syndrome especially in medical critically ill patients.     

Medical costs of managed care in patients with type 2 diabetes mellitus

The main objective of this study was to analyze the principal treatment cost drivers in patients with type 2 diabetes mellitus in a managed care setting. The study used retrospective integrated (linked) medical and pharmacy claims data for the calendar year 1995. The data were obtained from, and in cooperation with, the Hawaii Medical Service Association, Honolulu, Hawaii. The medical claims data included paid claims for services and procedures for diabetes and commonly associated comorbidities. Claims and associated costs for pharmacotherapy administered to the patient population were recorded in the pharmacy data. Patients aged > or =65 years were excluded because Medicare claims were unavailable for the type 2 diabetic population. The sample used in this study included 5171 patients. An ordinary least squares regression model was employed to identify principal cost drivers among the identified cohort to the managed care system. Independent variables in the analysis consisted of the presence or absence of a number of commonly observed comorbidities associated with diabetes mellitus (hypertension, hyperlipidemia, cardiovascular diseases, congestive heart failure, renal disorders, retinopathy, neurologic disorders, and any cardiac or noncardiac comorbidity combinations), pharmacologic therapy variables (insulin, oral medication, or both), a number of significant events (hospitalization, dialysis, hemoglobin A1c testing, and eye examination), patient enrollment category (fee-for-service vs a capitated system), and patient age and sex. The dependent variable was the natural logarithm of total medical costs of treatment for diabetes and commonly observed comorbidities. Results showed that among comorbidity variables, the 3 largest treatment cost drivers for patients with type 2 diabetes were the presence of neurologic disorders, renal disorders, and any comorbidity combination (cardiac or noncardiac or both), in decreasing order of significance. Similarly, higher costs of treatment were associated with episodes of hospitalization, use of antidiabetic medication, dialysis services, and hemoglobin A1c testing. Whether the patient was being treated under a capitated provider payment system or a fee-for-service system did not have any significant impact on the medical costs of diabetes-related treatment. Age was positively associated with these costs, indicating that older patients were more likely to incur higher costs to the system. The overall explanatory power of the model was 40%. In summary, unless diabetes is properly managed and glucose levels monitored, some component of an integrated health system (hospital vs pharmacy) necessarily bears financial risk. An understanding of the underlying cost distribution for a chronic disease could help in targeting interventions, integrating disease-management services, and managing the formal structure of the health plan being considered.     

The elderly neuroscience patient: implications for the critical care nurse.

The elderly patient may present to the critical care unit with neurologic deficits such as acute confusion, loss of consciousness, or signs of a cerebrovascular accident. Recognizing the normal age-related changes that occur in the nervous system enables the critical care nurse to evaluate the patient's response to neurologic disorders. The normal neurologic changes associated with aging provide implications for assessment, response to the critical care environment, and the time needed for education and rehabilitation. Other changes, especially decreased immunity, malnutrition, and pulmonary and cardiac pathology, significantly increase the risk for morbidity and mortality after an acute neurologic event. Changes in pharmacokinetics and the likelihood of polypharmacy in the older patient greatly increase the risk for complications and side effects of the commonly used treatments. Important elements of nursing management for the elderly neuroscience patient include performing an accurate neurologic assessment, including noting changes in cognition, observing for adverse drug reactions, optimizing ventilation, and maximizing mobility and nutritional status. This article focuses on these aspects of nursing care for the elderly neuroscience patient.     

Sleep in patients with neurologic and psychiatric disorders

Given the widely recognized association between many neurologic and psychiatric disorders and significant sleep disturbances, the International Classification of Sleep Disorders Diagnostic and Coding Manual recognizes "Sleep Disorders Associated with Mental, Neurologic, or Other Medical Disorders" as one of four major classification categories. Such sleep disturbances may exacerbate symptoms of the underlying neurologic or psychiatric disorder or produce further adverse medical, behavioral, or psychosocial consequences. Therefore, adequate assessment and recognition of sleep disturbances in these populations is essential. This article includes a summary of neurologic systems influencing sleep that may be affected by neurologic and psychiatric disorders, followed by a brief review of sleep disturbances associated with many common neurologic and psychiatric disorders.     

Understanding the patient with migraine: the evolution from episodic headache to chronic neurologic disease. A proposed classification of patients with headache

Traditionally, episodic primary headache disorders are characterized by a return of preheadache (normal) neurologic function between episodes of headache. In contrast, patients with chronic headache often do not return to normal neurologic function between headache attacks. This article proposes that the evolution from episodic migraine to chronic headache may parallel the neurologic disruption observed during the progression of an acute migraine attack and that changes in baseline neurologic function between episodes of headache may be a more sensitive indicator of headache transformation than headache frequency alone. Early recognition of nonheadache changes in nervous system function may offer a more sensitive and specific approach to migraine prevention.     

Surgery in the patient with neurologic disease

Patients with neurologic disease who require surgery present distinct issues and challenges for the medical consultant. Although it is not possible to offer a unified approach to neurologic patients, the primary care consultant should understand the clinical issues that are common to these patients, and the individual considerations necessitated by the nature of the neurologic disorder and the clinical characteristics of the patient. The preoperative evaluation combines elements of literature evidence on risk assessment with a thorough understanding of the planned procedure and local practice patterns, and clinical judgment as to the estimated risk-benefit ratio. Perioperative management necessitates attention to many general principles of perioperative care, such as awareness of the potential for cardiopulmonary complications and the need for DVT prophylaxis. In addition, there are management issues for neurologic patients, such as blood pressure control and evaluation of hyponatremia, which may differ from other surgical patients. In these circumstances, the interaction of the neurologic condition with the medical condition and the implications of treatment on the underlying neurologic process also need to be considered.     

Acute Onset Headache With Neurologic Impairment

Patients with acute neurologic conditions presenting to the emergency department, urgent care, or medical outpatient clinic can be a challenge to the medical provider. Many neurologic disorders warrant decisive action and collaboration with appropriate higher levels of specialty care for optimal patient outcomes. Initial management is made by exclusion, warranted by a complete history and physical examination, so as not to miss any key findings with this elusive disorder. Understanding the most significant presenting signs and symptoms of neurologic presentations led the provider to the appropriate questions in order to identify the differential diagnoses.