Volume 68, Issue 6 Louisville Medicine | Page 17

matory cells such as CD8 + B cells , monocytes , macrophages and microglia . This results in damage to myelin and axons . Pathological features include cytokine damage , antibody activity , complement damage , oxidative stress and mitochondrial dysfunction .
An additional risk factor for MS and increased disability is a low level of Vitamin D ; now MS patients are treated to maintain levels between 50 and 80 nanograms / milliter .
Multiple sclerosis at onset may follow variable patterns . The most common ( almost 85 %), is relapsing and remitting , with symptoms followed by a remission followed by a relapse - at variable intervals . In a much smaller percent , classified as primary progressive multiple sclerosis , symptoms never remit with progressive disability . Since the development of disease modifying therapies , we have seen a delay from 15 to now 25 years of disease duration prior to more severe progression . Now , 50 % of patients take much longer to develop secondary progressive MS . This is a pattern where the patient will have progressive disability , usually deterioration of gait , balance and cognitive decline , but without clear exacerbations and without inflammatory markers such as new MS plaques on MRI scanning .
A fourth pattern is relapsing progressive . An MS relapse represents inflammation along nerves and myelin with new or worsening symptoms and or neurological signs that must be present for at least 24 to 48 hours without any signs of infection or fever . A pseudo-exacerbation is not caused by new damage but may represent reappearance of prior symptoms . Most common etiologies include an occult urinary tract infection , excess exercise , other systemic illness , increased environmental temperatures , depression and stress . Exacerbations are often preceded or accompanied by an exacerbation of MS fatigue .
Severe MS relapses or exacerbations are often treated with steroids usually IV Solu-Medrol 1 g / day , three to five days in duration . Occasionally treatment may include Decadron or Acthar ( longer-acting injectable corticotropin ). Less severe exacerbations may be treated with oral steroids , 4 mg Solu-Medrol dose packs , two at the same time . A very severe exacerbation might require plasmapheresis or intravenous immunoglobulin ( IVIG ).
There has been no effective evidence-based therapy for multiple sclerosis until recent times . In 1970 , steroids or ACTH documented shortening the course of an exacerbation or relapse but not altering ultimate outcome . In 1993 , Betaseron , a high dose , high frequency interferon , was the first disease modifying therapy documented to reduce relapses and MRI plaque acquisition but available only by lottery until 1996 . In 1995 , Copaxone , a complex myelin analogue protein was certified . In 1996 , Avonex , a low dose , less frequent interferon became available . In 2002 , Rebif another high dose , high frequency interferon was approved . All of these therapies were given by injection . In 2010 , the first oral drug Gilenya appeared , followed in 2012 with Aubagio . Subsequently , new therapies of various mechanisms and toxicities appeared , leaving patient and doctor now with 23 choices , including the CD20 B cell-targeted
ALL IN THE HEAD monoclonal antibody , Ocrevus . Initial therapies were directed at T cell mechanisms and were effective for a relapsing remitting course . Subsequent addition of B cell modulation has resulted in the response of progressive components . Although no multiple sclerosis cure has yet been achieved , we are very close to drug therapies that result in no disease activity : that is no relapses , no new plaque acquisition on MRI scan and no disability progression .
It has become increasingly complex to select disease modifying therapies . The choice has to be made by an informed patient with extensive physician guidance , outlining effectiveness versus immune-suppression , side effect and safety issues . Costs can run high . Factors may include significant fetal side effects important for young women desiring to have a family or underlying systemic factors such as hepatic disease , hematologic disorders or depression . Patient choices are also modified by parenteral versus oral administration and insurance coverage . An entire article would be necessary for specific treatment options and symptomatic therapy .
The management of an MS patient is challenging , but with a combination of a careful history and physical examination with disease correlation of anatomy , physiology , immunology and the ability to have a close patient relationship has therapeutic potential . In addition to continuing research for additional disease modifying therapies , there is active research for medications that might result in remyelination and drugs that might modify the usually later , noninflammatory degenerative changes which affect nerve cells and axons , resulting in cognitive decline . The early course of multiple sclerosis is an inflammatory process with predominant demyelination and MRI evidence of plaque acquisition . Later , cell body and axonal pathology is noted with evidence of atrophy but not myelin loss . Although this is a recent appreciation of the degenerative pathology , Charcot made note of this in his pathologic examinations . There is recent attention to biomarkers for activity and presence of disease such as neurofilament light chain determination .
Treating the MS patient is certainly a team approach with primary care , looking for systemic disease - particularly urinary tract infections - as a cause for exacerbation or pseudo-exacerbation . Obstructive sleep apnea must be ruled out when there is an unexplained increase in spasticity . We must assure maintenance of vitamin D levels for the MS patient to be 50 – 80 nanograms / milliliter , and provide support , education and help with the family ’ s understanding of disability that may “ come and go ” but remains a constant risk . Patient education includes the benefit of diet , weight reduction , low-salt intake and smoking cessation , and exercise and fitness have documented benefit .
Compared to the treatment we could offer in my youth , now it is a matter of fine discernment of the suitable and affordable medication and biologic agent . It ’ s been a long road .
Dr . Meckler , FAAN is a practicing neurologist with special interest in multiple sclerosis and neuroophthalmology at Norton Neurology Services .
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