Combination total lymphoid irradiation and low-dose corticosteroid therapy for progressive multiple sclerosis

Cook, Stuart D.; Devereux, C.; Troiano, Raymond; Bansil, S.; Zito, George; Sheffet, Alice J.; Jotkowitz, A.; Rohowsky‐Kochan, Christine; Dowling, Peter C.

doi:10.1111/j.1600-0404.1995.tb06984.x

Cited by 4 publications

(5 citation statements)

References 12 publications

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“…In an open trial, the effect of TLI combined with a 1-year course of low-dose prednisone was compared to the effect of sham TLI and TLI only in a prior double-blind study of patients with progressive MS [125]. Twenty-seven patients with progressive MS received TLI plus low-dose corticosteroids.…”

Section: Cladribine (2-chlorodeoxyadenosine)mentioning

confidence: 99%

Multiple sclerosis: Immune mechanism and update on current therapies

1995

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Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) afflicting approximately 250,000 individuals in the United States. This inflammatory disease has variable clinical manifestations, ranging from a relapsing-remitting course to a chronic progressive disease. Approximately one third of MS patients have chronic progressive disease often leading to severe impairment of mobility, paralysis, poor vision, and disturbances of bladder and bowel function. Although the etiology and pathogenesis remain unknown, accumulating evidence supports the hypothesis that exposure to an as-yet-unidentified infectious agent(s) triggers an aberrant immune response against self nervous tissue in genetically susceptible individuals. The tenfold higher concordance rate for MS in monozygotic twins compared to dizygotic twins, the increased incidence of MS in women compared to men (2:1), and the familial and racial occurrence of MS provide strong evidence that genetic factors influence susceptibility to MS. The major predisposing genes in MS are the human leukocyte antigen (HLA) class II molecules, DR15 and DQw6, molecularly defined as HLA-DRB1, 1501-DQA1 0102-DQB1 0602. In certain ethnic groups, MS susceptibility is more strongly associated with other DR molecules. Environmental factors are also believed to play a role, as suggested by the unique worldwide prevalence, migration effects, and epidemiological studies. Increased serum and cerebrospinal fluid antibody titers to numerous viruses have been reported; however, there have been no confirmed studies detecting viral RNA or antigen in MS brain tissue. At the present time, no known treatment can significantly alter the progression of MS. Based on the postulate that MS is an autoimmune disease associated with abnormalities in immunoregulation, a number of different immunosuppressive and immunomodulating agents have been tested as therapeutic modalities. In this article, we review the circumstantial evidence suggesting that immune system abnormalities are associated with the disease process, and provide an update on current therapies used in MS.

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Section: Cladribine (2-chlorodeoxyadenosine)mentioning

confidence: 99%

Multiple sclerosis: Immune mechanism and update on current therapies

1995

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“…Side effects were common and included infections and amenorrhea. Almost all patients became cushingoid and there were several fractures, and 1 patient died from unknown causes (107).…”

Section: Miscellaneousmentioning

confidence: 99%

The management of multiple sclerosis: Current and future therapies

Stevenson¹,

Thompson²

1998

Drugs of Today

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Management of the patient with multiple sclerosis (MS) encompasses a number of distinct, if overlapping, areas. They include anticipation and prevention of problems, symptom control, drug therapies aimed at reducing disease activity and finally, rehabilitation and service delivery. The recent advent of new immunosuppressant treatments for MS is extremely exciting. Beta-interferons (1a and 1b) are now licensed worldwide and glatiramer acetate (Copaxane ®) is in use in the United States. Many more drugs, including intravenous immunoglobulin, mitoxantrone, methotrexate and cladribine, are undergoing trials and some are showing promising results. Future therapies with monoclonal antibodies and adhesion molecules are also undergoing extensive research. Realistically, however, these new treatments aimed at reducing disease activity will have little impact on existing problems or the degree of disability. Consequently, much of the management of a patient with MS relates to control of the vast array of symptoms. These range from the obvious problems of weakness and spasticity, ataxia and sphincter disturbance, to less common but still important problems such as visual, cognitive, swallowing and respiratory difficulties. Some of the most common, and to the patient most disabling, symptoms are fatigue, thermal sensitivity and pain, areas often neglected by the physician in the face of more obvious physical needs. Much can be done for the patient in all areas. A combination of education, physiotherapy and drug therapy is usually required but occasionally there is a place for more invasive treatments such as intrathecal baclofen administration for severe spasticity or thalamic surgery for cerebellar tremor. A multidisciplinary team approach is essential in the overall management of the patient with MS,

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“…TLI is a time‐consuming treatment, but no delays in obtaining routine treatment were mentioned. The four MS trials were all small (with an average of 40 patients per trial), only one was multicentred 23 . The primary end‐points studied were the disease arrest rate or the absence of progression using the expanded disability status scale.…”

Section: Resultsmentioning

confidence: 99%

“…The least resemblance was probably that shown in one of the ARMD trails in which the treatment group underwent seven treatment sessions whereas the SRT group underwent only one and did not undergo CT simulation 11 . Others went to significant lengths to replicate the sound of the treatment, including the use of a pulse generator to create the sound of a linear accelerator 26 and using headphones to mask the sound of the active treatment by producing ‘white noise’ 23 . For lower energy treatments, shielding can be used to prevent the delivery of treatment whereas still enabling the machine to make its sound 19,28 .…”

Section: Discussionmentioning

confidence: 99%

Use of ‘sham’ radiotherapy in randomized clinical trials

Schwarz

Christie

2008

J Med Imag Rad Onc

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The objective of this systematic review was to identify quality trials that use sham radiotherapy in their design and review them to determine its potential value. The Cochrane Library, Pubmed and a Reference Search served as data sources. Trials were included if they met a minimum quality score of 3 on a validated assessment instrument (which assesses randomization, control and blinding) and if they compared sham radiotherapy to active treatment. External beam therapy and brachytherapy trials were considered. Twenty-six trials were identified, collectively including 2663 participants in the period of 1970-2004. All the trials studied the value of radiotherapy for treatment or prevention of benign diseases, including multiple sclerosis, coronary artery restenosis, age-related macular degeneration and Graves' ophthalmopathy. There were no trials relating to the use of radiotherapy in the treatment of malignancy. This review showed that it is possible to carry out sham radiotherapy with due regard for ethical concerns, with effective blinding and high levels of patient acceptance. Large sample sizes with multicentre trial designs were achievable. Although the statistical philosophy for using sham radiotherapy in trials is legitimate, it is no longer routinely used.

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Combination total lymphoid irradiation and low-dose corticosteroid therapy for progressive multiple sclerosis

Cited by 4 publications

References 12 publications

Multiple sclerosis: Immune mechanism and update on current therapies

Multiple sclerosis: Immune mechanism and update on current therapies

The management of multiple sclerosis: Current and future therapies

Use of ‘sham’ radiotherapy in randomized clinical trials

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