While current immunomodulating drugs aim to reduce multiple sclerosis (MS) exacerbations and slow disease progression, rehabilitation aims to improve and maintain the functional abilities of patients in the face of disease progression. An increasing number of journal articles are describing the value of the many rehabilitation interventions that can be used throughout the course of the disease, from the initial symptoms to the advanced stages. An integrated team of healthcare professionals is necessary to address a myriad of problems to reduce impairments, disabilities, and handicaps. The problems may be related to fatigue, weakness, spasticity, mobility, balance, pain, cognition, mood, relationships, bowel, bladder, sexual function, swallowing, speech, transportation, employment, recreation, and activities of daily living (ADL) such as dressing, eating, bathing, and household chores. The team can help prevent complications and secondary disabilities, while increasing patient safety. Improving neurologically related function, maintaining good relationships, and feeling productive and creative adds enormously to the quality of life of people with MS and their families. Rehabilitation is more than an ‘extra’ service that is given after medical therapies; it is an integral part of the management of the diverse set of problems encountered throughout the course of the disease. An interdisciplinary team may have many members, including physicians, nurses, physical therapists, occupational therapists, speech and language pathologists, psychotherapists, social workers, recreational therapists, vocational rehabilitation therapists, patients, families, and other caregivers.
Multiple sclerosis; rehabilitation
The management of multiple sclerosis (MS) revolves around disease management, symptom management, and person management. Of these, symptom management takes up the bulk of the time of the practicing physician. Some symptoms are easily managed whereas others are more difficult. Decisions have often to be made on whether to treat or to wait and watch. This article discusses the varied symptoms of MS and the approaches to management, which involves rehabilitation, pharmacological treatments, and surgical procedures. The skilled physician managing MS should be familiar with the multiple approaches to improving the quality of life of those with MS. After the diagnosis has been established and the decisions regarding treatment approaches have been made, the talk in a typical office appointment for MS usually turns to symptom management. Thus, the majority of management decisions made by the clinician revolve around that important topic. It is symptom management that will determine quality of life for those with MS, It is the basis for improving function, and, up until twenty years ago, it was the only basis for treating MS. Now, however, we can approach treatment by disease management, symptom management, and person management. The MS specialist must be well versed in all three areas.
Management; multiple sclerosis; symptom
The therapeutic options for multiple sclerosis are rapidly expanding. What was once seen as a disease with little hope for treatment is now a target of rapid drug development. Current therapies have demonstrated efficacy in limiting the impact of the disease, but none is fully effective in all patients. However, promising new treatments are on the horizon. In this review we will discuss potential novel immunomodulating drugs that are in advanced stages of investigation; these drugs include monoclonal antibodies, chimeric molecules, and oral therapies. The use of hematopoietic stem cells will also be discussed and, in addition, we will look farther ahead at possible novel targets for the development of new immunomodulatory or neuroprotective pharmaceuticals.
Drugs; investigational; multiple sclerosis; therapeutics
Since 1993, six disease-modifying therapies for multiple sclerosis (MS) have been proven to be of benefit in rigorous phase III clinical trials. Other agents are also available and are used to treat MS, but definitive data on their efficacy is lacking. Currently, disease-modifying therapy is used for relapsing forms of MS. This includes clinically isolated syndrome/first-attack high-risk patients, relapsing patients, secondary progressive patients who are still experiencing relapses, and progressive relapsing patients. The choice of agent depends upon drug factors (including affordability, availability, convenience, efficacy, and side effects), disease factors (including clinical and neuroimaging prognostic indicators), and patient factors (including comorbidities, lifestyle, and personal preference). This review will discuss the disease-modifying agents used currently in MS, as well as available alternative agents.
Disease-modifying agents; glatiramer acetate; interferon beta; multiple sclerosis therapy; natalizumab
A key component of multiple sclerosis is the occurrence of episodes of clinical worsening with either new symptoms or an increase in older symptoms over a few days or weeks. These are known as exacerbations of multiple sclerosis. In this review, we summarize the pathophysiology and treatment of exacerbations and describe how they are related to the overall management of this disease.
Exacerbation; management; multiple sclerosis; relapse; steroids
Magnetic Resonance Imaging (MRI) has brought in several benefits to the study of Multiple Sclerosis (MS). It provides accurate measurement of disease activity, facilitates precise diagnosis, and aid in the assessment of newer therapies. The imaging guidelines for MS are broadly divided in to approaches for imaging patients with suspected MS or clinically isolated syndromes (CIS) or for monitoring patients with established MS. In this review, the technical aspects of MR imaging for MS are briefly discussed. The imaging process need to capture the twin aspects of acute MS viz. the autoimmune acute inflammatory process and the neurodegenerative process. Gadolinium enhanced MRI can identify acute inflammatory lesions precisely. The commonly applied MRI marker of disease progression is brain atrophy. Whole brain magnetization Transfer Ratio (MTR) and Magnetic Resonance Spectroscopy (MRS) are two other techniques use to monitor disease progression. A variety of imaging techniques such as Double Inversion Recovery (DIR), Spoiled Gradient Recalled (SPGR) acquisition, and Fluid Attenuated Inversion Recovery (FLAIR) have been utilized to study the cortical changes in MS. MRI is now extensively used in the Phase I, II and III clinical trials of new therapies. As the technical aspects of MRI advance rapidly, and higher field strengths become available, it is hoped that the impact of MRI on our understanding of MS will be even more profound in the next decade.
Magnetic resonance imaging; multiple sclerosis; problem-oriented clinical approach
Technological advances have made it possible to examine the human cerebrospinal fluid (CSF) in a manner that was previously impossible. CSF provides a window into the changes that occur in the central nervous system (CNS) in health and disease. Through analysis of the CSF, we discern indirectly the state of health of the CNS, and correctly or incorrectly, draw conclusions regarding mechanisms of CNS injury and repair.
Objective, Materials and Methods:
To review the current state of knowledge of changes in the CSF in multiple sclerosis.
Establishing CSF markers that permit evaluation of the various biological processes in multiple sclerosis remains a challenge. Of all the biological processes, inflammatory markers are probably the best identified. Detection of oligoclonal immunoglobulin bands in the CSF is now established as the single most useful laboratory marker in the CSF to aid in the diagnosis of multiple sclerosis. Markers of demyelination, remyelination, neuro-axonal loss, neural repair and regeneration, and astrogliosis are only now being recognized. A good surrogate for any of these pathophysiological processes has not been defined to date.
The goal of future research is not only to define surrogate markers in the CSF for each of the above functions, but also to extend it to other more readily accessible body fluids like blood and urine. A synopsis of the current literature in most of these areas of CSF evaluation pertaining to multiple sclerosis is presented in this article.
Cerebrospinal fluid; multiple sclerosis
Pediatric multiple sclerosis (MS) represents a particular MS subgroup with unique diagnostic challenges and many unanswered questions. Due to the narrow window of environmental exposures and clinical disease expression, children with MS may represent a particularly important group to study to gain a better understanding of MS pathogenesis. Acute disseminated encephalomyelitis (ADEM) is more common in children than in adults, often making the differential diagnosis of MS, particularly a clinically isolated syndrome, quite difficult. Although both disorders represent acute inflammatory disorders of the central nervous system and have overlapping symptoms, ADEM is typically (not always) self-limiting. The presence of encephalopathy is much more characteristic of ADEM and may help in distinguishing between the two. Young children (under ten years old) with MS differ the most from adults. They have a lower frequency of oligoclonal bands in their cerebrospinal fluid and are less likely to have discrete lesions on MRI. Problems of cognitive dysfunction and psychosocial adjustment have particularly serious implications in both children and teenagers with MS. Increased awareness of these difficulties and interventions are needed. While clinical research on therapies to alter the disease course is limited, the available data fortunately suggests that disease-modifying therapy is well tolerated and likely to be effective. Ultimately, multinational research studies are necessary to advance our knowledge of the causes, symptoms, and treatment of pediatric MS and such collaborations are currently underway.
Pediatric multiple sclerosis
Neuromyelitis optica is an inflammatory demyelinating disorder of the central nervous system. The discovery of a specific antibody (NMO IgG /aquaporin-4 antibody) in patients with this condition has led to a marked revival of research on the disease. This article summarizes the major advances in neuromyelitis optica, particularly in the last 2 years, and supplements the previous review published in this Journal in 2007. Important among these developments are: the epidemiological studies, which have provided estimates of incidence and prevalence; identification of mutations in the aquaporin-4 gene; improved understanding of the effects of anti-aquaporin-4 antibody on astrocytes; roles of excitatory amino acid transporter type 2 and glutamate; requirement of aquaporin-4 to be in orthogonal arrays to be antigenic; recognition of the presence of aquaporin-4 antibody in patients with cancer and posterior reversible encephalopathy syndrome; possibility of monitoring the disease using the antibody, and the effectiveness of rituximab and mycophenolate in preventing relapses.
Aquaporin; multiple sclerosis; myelitis; neuromyelitis optica
The diagnosis of multiple sclerosis (MS) requires objective findings referable to the central nervous system. A wide differential diagnosis often has to be considered. Magnetic resonance imaging and electrophysiologic and cerebrospinal fluid studies can all contribute to an early definitive diagnosis. The McDonald diagnostic criteria for MS (2005) are the currently recognized MS diagnostic criteria. The clinical subtypes of MS and their diagnosis are discussed in this article. Being informed of the diagnosis may be a stressful experience for the patient and this is also dealt with.
Multiple Sclerosis; Clinical subtypes; diagnosis; diagnostic criteria
B cells have recently been identified as an integral component of the immune system; they play a part in autoimmunity through antigen presentation, antibody secretion, and complement activation. Animal models of multiple sclerosis (MS) suggest that myelin destruction is partly mediated through B cell activation (and plasmablasts). MS patients with evidence of B cell involvement, as compared to those without, tend to have a worse prognosis. Finally, the significant decrease in new gadolinium-enhancing lesions, new T2 lesions, and relapses in MS patients treated with rituximab (a monoclonal antibody against CD20 on B cells) leads us to the conclusion that B cells play an important role in MS and that immune modulation of these cells may ameliorate the disease. This article will explore the role of B cells in MS and the rationale for the development of B cell–targeted therapeutics. MS is an immune-mediated disease that affects over 2 million people worldwide and is the number one cause of disability in young patients. Most therapeutic targets have focused on T cells; however, recently, the focus has shifted to the role of B cells in the pathogenesis of MS and the potential of B cells as a therapeutic target.
B cells; multiple sclerosis; treatment
Multiple sclerosis (MS) is a suspected autoimmune disease in which myelin-specific CD4+ and CD8+ T cells enter the central nervous system (CNS) and initiate an inflammatory response directed against myelin and other components of the CNS. Acute MS exacerbations are believed be the result of active inflammation, and progression of disability is generally believed to reflect accumulation of damage to the CNS, particularly axonal damage. Over the last several years, the pathophysiology of MS is being appreciated to be much more complex, and it appears that the development of the MS plaque involves a large number of cell populations, including CD8+ T lymphocytes, B cells, and Th17 cells (a population of helper T cells that secrete the inflammatory cytokine IL-17). The axonal transection and degeneration that is thought to represent the basis for progressive MS is now recognized to begin early in the disease process and to continue in the progressive forms of the disease. Molecules important for limiting aberrant neural connections in the CNS have been identified, which suppress axonal sprouting and regeneration of transected axons within the CNS. Pathways have also been identified that prevent remyelination of the MS lesion by oligodendrocyte precursors. Novel neuroimaging methodologies and potential biomarkers are being developed to monitor various aspects of the disease process in MS. As we identify the pathways responsible for the clinical phenomena of MS, we will be able to develop new therapeutic strategies for this disabling illness of young adults.
Magnetic resonance imaging; multiple sclerosis; pathogenesis; review
The epidemiology of multiple sclerosis has been extensively investigated and two features have consistently emerged: marked geographical variation in prevalence and substantial familial clustering. At first sight, geographic variation would seem to imply an environmental cause for the disease, while familial clustering would seem to suggest that genetic factors have the predominant etiological effect. However, given that geographic variation in prevalence could result from variation in the frequency of genetic risk alleles and that familial clustering might result from shared environmental exposure rather than shared genetic risk alleles, it is clear that these crude inferences are unreliable. Epidemiologists have been resourceful in their attempts to resolve this apparent conflict between “nurture and nature” and have employed a whole variety of sophisticated methods to try and untangle the etiology of multiple sclerosis. The body of evidence that has emerged from these efforts has formed the foundation for decades of research seeking to identify relevant genes and this is the obvious place to start any consideration of the genetics of multiple sclerosis.
Genetics; genome-wide association study; multiple sclerosis
The apnea test is a mandatory examination for determining brain death (BD), because it provides an essential sign of definitive loss of brainstem function. However, several authors have expressed their concern about the safety of this procedure as there are potential complications such as severe hypotension, pneumothorax, excessive hypercarbia, hypoxia, acidosis, and cardiac arrhythmia or asystole. These complications may constrain the examiner to abort the test, thereby compromising BD diagnosis. Nevertheless, when an appropriate oxygen-diffusion procedure is used, this technique is safe. We review here the prerequisites to begin the test, its procedure, potential complications, and the use of alternative ancillary tests. We recommend that the apnea test be retained as a mandatory procedure for the diagnosis of BD. In those situations when the apnea test is terminated by the examiner for some reason or when it is impossible to carry it out in a patient due to the presence of some pathologic condition, alternative ancillary tests should be used to confirm BD.
Ancillary tests; apnea test; brain death
Paraplegia due to a spinal cord epidural mass is an extremely rare presentation of undiagnosed leukemia. We are reporting a case of 14-year-old girl, who presented with paraplegia due to thoracic epidural mass, as the initial presenting manifestation of acute myeloid leukemia. Granulocytic sarcoma or chloroma should be considered in the differential diagnosis of an epidural mass in patients with or with out leukemia granulocytic sarcoma, which are rare extramedullary tumor-like proliferation of myelogenous precursor cells that may de novo precede acute leukemia or coincide with the first manifestation or relapse of acute myeloid leukemia.
Acute myeloid leukemia; chloroma; granulocytic sarcoma
A mobile plaque in the carotid artery is an uncommon entity, usually detected incidentally on a carotid duplex scan or angiography. It is associated with an indeterminate risk of an embolic stroke and should be managed on an emergent basis. We report here a case of a mobile plaque in the internal carotid artery that was detected serendipitously in a carotid duplex scan.
Carotid duplex; mobile plaque