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The Transverse Myelitis Association www.myelitys.org "Transverse Myelitis" chapter on the current treatment of neurological syndromes , Sixth Edition Douglas Kerr MD / PhD Publishers Johnson RT, Griffin, JW, & McArthur, JC Mosby P ress, 2001 Clinical features transverse myelitis (TM) is an acute inflammatory process affe cting a focal area of the spinal cord. Is clinically characterized by progress a nd acute or subacute symptoms and signs that motor and sensory dysfunction of th e autonomic nerves and nerve strokes marrow. In general, sensory dysfunction fol lowing a gradual increasing trend until reaching a peak, and the spinal MRI and a lumbar puncture can identify an acute inflammation. To make a definite diagnos is of MT will be excluded other neurological diseases known such as the compress ive myelopathy, syphilis, cancer, or arterio venous malformations spinal AVM. Th e transverse myelopathy is generally defined as acute non-compressive myelopathy whose symptoms suggest a location rostral limited. Symptoms can have a temporal progression in some subjects ranging from minutes to several hours, others for days to weeks. When the highest deficit has reached roughly 50% of patients lost motor function of lower limbs, almost 100% have urinary dysfunction different l evels and between 8094% report numbness, paresthesia or dysesthesia. The autonom ic symptoms albeit in varying degrees are: urinary urgency, bowel or bladder inc ontinence, difficulty or inability to empty the bladder and feeling of incomplete emptying or constipation. Etiology of TM intestinal There is a unique etiology for MT, but frequently the clinical syndrome may be d ue to neural tissue damage caused by an infectious agent or immune system or bot h. Parainfettiva Many clinical cases have their origin and often take place beca use of infection in the lungs or gastrointestinal syndromes. Minor are cases in which the MT is directly caused by a bacterial infection of the central nervous system (CNS). A variable percentage between 30 and 60% of patients are subject b efore 'attack (from 3-8 weeks) for a course of infection confirmed by serologica l evidence of acute infection (rubella, measles, mononucleosis, influenza, enter oviruses, mycoplasma or viral hepatitis A, B and C). Other pathogens such as Her pes virus (CMV cytomegalovirus or HHV-5, the varicella zoster virus VZV, herpes simplex virus HSV1 and HSV2, herpes hhv6 human virus, Epstein-Barr Virus EBV vir us leukemia T-cell HTLV-1 and Human Immunodeficiency Virus HIV-1) cause a direct infection of the bone and can cause the MT. The Borrelia burgdorferi (Lyme dise ase neuroborreliosis) and Treponema pallidum (syphilis) have been identified as possible fb / September 2007 Article Page 2 direct causes of infection to the CNS and MT. MT was also associated with system ic autoimmune diseases such as Systemic Lupus Eritoematoso SLE. Many patients ha d a spinal focal vasculitis associated with symptoms of active SLE, while other

patients showed the presence antiphospholipid antibodies or other types always r elated to them such as beta-2-glycoprotein I. Both types of antibodies are relat ed to a prothrombotic state and microvascular thrombosis, and may perhaps be ind icative of a pre-existing medical condition. For Transverse myelopathy patients is often ultimately diagnosed with Multiple Sclerosis MS. Important,in the formu lation of differential diagnosis of TM is ischemia of the spinal cord. have been described in patients with an initial diagnosis of MT, myocardial arterial, ven ous and brain (stroke). infarction caused by occlusion of spinal cord blood is v ery common in the anterior spinal area and cause damage to the corticospinal seg ment, the nerve fibers descending urinary and intestinal tract and spinothalamic tract without affecting the functionality of the spine back. Along the rostro c audal axis, the Most arterial strokes is T4T10 region due to poor collateral blo od flow in this area of the body that normally receives a double flow of blood. venous infarction can also occur with progressive neurological deficits and ofte n with a hemorrhagic transformation of reflexive persistent venous hypertension. In addition, long-lasting arteriovenous fistulas, resulting in a recurrent or i ntermittent myelopathy that occurs usually in males between 40 and 70 years of a ge. The diagnosis described above, should be considered for every patient with m yelopathy applicant since surgery or therapy endovasclare dell'aneurismo (emboli sm) may, some people restore neurologic function assessment of patients with TM For each patient who is suspected of acute spinal cord dysfunction should be guaranteed a timely assessment. Since rarely, at the beginning of the disease, occur simulta neously in the three types of dysfunctional patients (motor sensory and autonomi c), physicians should recommend in advancing our clinical investigation, apply a n evaluation criterion based on indicators with low threshold. Unfortunately, ra dicular back pain is one of the earliest and most common non-specific symptoms o f patients with TM. However, if a patient complains of difficulty minizione, inc ontinence than ever before or cross-sensory pain (similar to a compression banda ge, pain or numbness) the doctor should immediately provide emergency depth surv eys. Similarly, symptoms characterized by bilateral weakness in both lower limbs in association with the symptoms above, should press for a rapid assessment of more detailed diagnosis. Many patients who experience numbness in developing rap id progress is mistakenly diagnosed with Guillain-Barre Syndrome (GBS ). However , in contrast to the SGB, the MT is characterized by paralysis of cranial nerves , while GBS occurs rarely with urinary dysfunction and pain similar to compressi on. The initial evaluation of patients with a progressive myelopathy possible ca use strutturalemeccanica, such as slipped disc, a pathological vertebral fractur e, tumor, metastasis or spondilostesia (see algorithm Acute MT). Theoretically, an MRI MRI performed using liquid Contrast (gadolinium) should be performed a fe w hours fb / September 2007 Article Page 3 distance the onset of symptoms. In is not possible to have a timely MRI, a compu ted tomography myelography or computed tomography cord, can be a viable alternat ive. Both tests, however, have the disadvantage of not being relevant to an asse ssment of pathological intramedullary, is also a good idea to submit, following the acute phase, all patients with a diagnosis of an MT MRI as soon as possible. If causes and impediments to force a delay time of clinical imaging and patient manifests a rapidly progressive myelopathy,is recommended for administration of methylprednisolone in the physician: less than 3 hours of symptom onset 30mg/kg (in a single dose) in the first hour and 5.4mg/kg/ora subsequent 23 hours, at a distance of 3-8 hours of the first symptoms administer a single dose 30mg/kg, f ollowed by 5.4mg/kg/ora subsequent 47 hours. If you have identified a structural -mechanical origin of myelopathy, it must necessarily be considered a neurosurgi

cal intervention. Conversely, if not there struttuali-mechanical causes in patie nts with progressive myelopathy Transverse acute or sub-acute, therapeutic treat ment can be adjusted according to potential causes. should be carried out routin e tests such as a lumbar puncture, examination of cerebrospinal fluid, the searc h for oligoclonal bands, IgG index, CRP (C reactive protein), the antibody Lyme and mycoplasma and laboratory tests VDRL Venereal Disease Research. Although thi s list is not exhaustive, identifies those potentially treatable causes of Trans verse Myelopathy. A Depending on the clinical picture, further clinical trials c an give more guarantees additional serological diagnosis. During the period of w aiting for results of serology and PCR tests, often to administration of acyclov ir at a dose empirically (10 mg / kg intravenously three twice daily for 14-21 days), especially if before the myelitis, there is a histo ry of burning, radicular pain or radicular zoster. If the patient has clinical o r radiological evidence of mycoplasma, therapeutic treatment for the MT should i nclude doxycycline (100mg orally twice daily), azithromycin (500mg once daily an d 250mg next day orally). Similarly, the choice of treatment modalities, should be considered a possible addition to the intravenous ceftriaxone empirically use d for the diagnosis of Lyme disease (neuroborrelliosi). Immunocompromised Patien ts with a history of CMV (cytomegalovirus) or retinopathy poliradiculopatia, sho uld be administered ganciclovir (5 mg / kg intravenously every 12 hours.) Consid erations for microbiological etiology of TM should not deter the aggressive dose s of corticosteroids. The intravenous administration of high doses of corticoste roids has often starts after the formulation of a diagnosis of MT, several studi es have demonstrated the efficacy of corticosteroids in improving the ability to walk and recovery of motor function of the patient. Many doctors begin treatmen t by administering metilpredinosole (1000mg per day intravenously for 5 days), t his regimen should be applied to most patients as soon as you made a tentative d iagnosis MT. Weinshenker and his colleagues have reported that some patients wit h idiopathic inflammatory demyelination, intolerant to steroids, responding rath er well to plasmapheresis or apheresis therapy. "Consequently, in our clinic, pa tients suffering from acute MT has implemented a regimen based on a 5-day course of methylprednisolone sodium hemisuccinate (solumedrol) intravenously followed by plasmapheresis to a plasma volume 1.1 every other day for two fb / September 2007 Article Page 4 weeks. Currently, it is unclear when to start apheresis therapeutic in our clini c before starting apheresis, wait a week after the end of steroid treatment. In patients with MT with a known or suspected connective tissue disease, as such as SLE,the diagnostic investigation should encourage the search for evidence indic ating the presence of a systemic vasculitis or a predisposition based on pro-thr ombotic antiphospholipid antibodies. The suspicion of a vasculitic etiology may have a basis where there is evidence of: reduction of the concentration of C4 in the system Further, under anti-nuclear antibodies ANA levels, hematuria (blood in urine), high erythrocyte sedimentation rate ESR or other systemic diseases th at show the condition of SLE. For the patients in line with this clinical pictur e, should be administered intravenous high dose corticosteroids and should be ma de to perform the appropriate considerations of bolus doses of cyclophosphamide (500-1000mg/m2). may subsequently be administered monthly at a dose adjusted so as to obtain a low threshold white cell count (3000-4000/m3). Patients with SLE who have antiphospholipid anticporpi, often report previous arterial or venous t hrombotic events, fetal loss and livedo reticularis (a design skin due to dilati on of the capillary network, which determines the a drawing type reticular skin of blue). These patients usually require in order to prevent another attack of M T, a drug therapy anticoagulants. Treatment of the chronically ill MT Since MT i s usually a monophasic disease, treatment of patients following an acute attack

with consequences, is focused in the management of symptoms. Many management str ategies are similar to those applied to patients with traumatic spinal pathologies, which are not subject to this article (see Chapter X and the algorithm of TM Chronicle, reported later). In the management of patients with TM, to be followed several guiding principles . If the patient, although with difficulty, be able to hire or standing or walki ng, must strive to do at least daily. The vertical upright posture is critical b oth for the good preservation of bone structure and skeletal muscle for reactivi ty of the circulatory system. also decreases the incidence of urinary tract infe ctions and the possibility of deep vein thrombosis. Patients may need support or thopedic aids, such as a support structure for standing or special orthopedic cr utches; may also be necessary aquatic therapy (see details below) that may facil itate the movement. Patients with TM should also undergo medical checks for depr essive syndromes as well as being often recurrent, is an impediment to full subj ect to compliance of the rehabilitation regimens, negatively influencing the rec overy process. Another disorder that often afflicts people with MT have sexual d ysfunction, some patients suffering from erectile dysfunction, found an overall improvement of the function sex, taking sildenafil (Viagra) (50100mg 1 hour befo re sexual activity). Furthermore, should be screened for osteoporosis although y oung, as reduced or lack of ability to support your body weight can cause accele ration of bone erosion. An evaluation of bone density followed by a regimen (Ca + + 1000mg per day plus 400 IU vitamin D / d and possibly bisphosphonates reduce the likelihood of pathologic fractures and functional deterioration. fb / September 2007 Article Page 5 Often, the resulting urinary dysfunctions that plague some patients, evolve over time ATONIC bladder spasticity in it,episodes of incontinence. This trend is ca used by neurogenic detrusor overactivity (the biceps of the bladder), which is a consequence of damage to cargo of nerve fibers that regulate urination descenda nts. Patients with sacral MT (interest medullary cone) can bring lasting consequ ences, such as the inability to contract the bladder, where the lower motor neur ons that control the bladder have been damaged. It will be necessary to assess t he damage to the upper, an ultrasound impairment that should ideally be performe d in the first three months, urodynamic tests whose objective is the assessment of pressure storage and emptying, as well as instant sfinterometria voiding, wil l instead be carried out within the first six months subsequent to the onset of MT . These clinical conditions can lead to chronic damage of both urinary tract (upper and lower) and are often silent conditions. These clinical evaluations, h elp the doctor to formulate a drug therapy aimed at maximizing the urinary funct ion. The aim of effectively managing Urinary dysfunction is to reduce the pressu re storage of urine (<10-15cm in 20 hours), to lower the discharge pressure (<40 -60cm in 20 hours in men and <20-30cm in 20 hours in females) and to reduce the residual volume (<50 100cc). A simple detrusor overactivity can be treated with anticholinergic drugs, such as oxybutinina (Ditropam) extended release (5-10mg o nce or twice a day ) hyoscyamine (0.15-0.3 mg orally orally four times) than tol terodine (1-2mg twice daily) or propantheline (15mg orally every 4-6 hours). sfi nterometria While the results are instantaneous voiding required to assess the n eed for urological consultation and medication combined. Sacral nerve stimulation is a p romising new therapy, which may allow the patient to reduce or eliminate the nee d for intermittent catetarizzazione. Patients often reported as a result of TM, a permanent physical weakness. Following the traditional therapeutic strategies for rehabilitation is possible to obtain significant functional improvements, it recommends an application of attack. Hydrotherapy rehabilitation is beneficial

for patients with MT and in particular improves cardiovascular function, reduce spasticity, restores ability to take the vertical upright position and keep a se nse of self. Some patients reported significant improvements in terms of physica l strength and urinary function assuming fampridina (4-aminopyridine). This drug blocks potassium channels that inhibit the electrical repolarization neurons. T he drug then amplifies the conduction of nerve damage. It should be administered with caution because the potential side effects include paresthesia, vertigo an d dizziness, agitation, increased blood pressure, insomnia and headaches. The re commended starting dose of fampridina is 10mg daily, titrated up to a total dail y dose of 0.5-0.7mg/kg daily. Doses greater than 0.8mg/kg daily gave evidence of heart attack and must consequently be avoided. The pain or are lying the most d ebilitating long-term consequences that affect approximately 40% of patients wit h MT. The symptoms are often managed with the administration of gabapentin (up t o 4800mg a day divided into three or four doses), carbamazepine extended release (up to 1200mg per day in two doses)nortriptyline (up to 100mg per day administe red in the evening) or tramadol (up to 400mg daily divided into three fb / September 2007 Article Page 6 or four doses). Usually opioids are no more effective drugs and logistics as far as possible should be avoided because they cause side effects such as constipat ion and urinary retention. In some subjects, there was a considerable relief wit h fewer side effects administering opiates side intrathecal, ie through a pump i mplanted. In some local areas suffering from dysesthesia can be applied effectiv ely, a transcutaneous electrical stimulation (SETC). Constipation, for some pati ents MT is a perennial problem and often requires a combination of digital chron ic stimulation or manual cleaning of the rectum and laxatives. The goal of manag ing bowel function is regular evacuation of feces or fairly compact compact with out the need of chronic stress. Many patients respond quite well to a treatment regimen of Dulcolax (two confetti orally every evening). In addition, the interm ittent use of Bisacodyl in aqueous solution is highly effective in most patients . Spasticity affects virtually all patients with TM and often beyond recovery. P atients may report stiffness and soreness, tension or painful spasms of the butt ocks and legs. Spasticity may limit walking especially on undulating surfaces an d then walk to stimuli that create a destabilizing posture. In 60% of subjects, such as therapy Home is often used baclofen (an initial dose of 10mg to 100mg da ily). The fatigue and progressive development of a general physical weakness may be its potential effects. The Tizanidine (at an initial dose of 2mg per day up to 24-32mg daily in three divided doses) is a drug that inhibits the presynaptic motor neurons in the spinal cord and is theoretically more specific for interne urons, compared with baclofen. tiznadina Consequently, it could more easily caus e weakness, but its use is still rather limited side because of the fatigue that comes from his administration. The administrati on of diazepam (starting with a dose of 5mg, up to 30-40mg in three divided dose s) can be very effective in those patients with spasticity, who do not respond t izanidine it to them to baclofen. Patients with functionally limiting spasticity who do not respond to treatment by mouth, the intrathecal administration of bac lofen is a viable alternative. Following a clinical trial on the administration of baclofen through a lumbar puncture (50mcg and case of lack of efficacy from 7 5 to 100mcg) is an implanted subcutaneous pump which does received baclofen dire ctly to the cerebrospinal fluid from the lumbar region. The pumping speed can be adjusted from the outside, the pump must be refilled, percutaneously 3-5 times per year. Side effects include infection and weakness, but fatigue and worsening of constipation are generally rare. Other resources Transvere Johns Hopkins Tra nsverse Myelitis Association www.myelitis.org Myeopathy Center www.med.jhu.edu / jhtmc

fb / September 2007 Article Page 7 Figure 1 - Assessment of Patients with Acute Myelopatia ANA antinuclear antibodies ESR Erythrocyte Complement CH50 hemolytic activity GP I VZV glycoprotein I / Varicella Zoster Virus HSV / Herpes Simplex fb / September 2007 Article Page 8 Figure 2 - Management of patients with TM fb / September 2007