Acute disseminated encephalomyelitis.
This article describes the course of a young female diagnosed with acute disseminated encephalomyelitis (ADEM) with an atypical presentation. TD is a 22-year-old female who presented to the emergency department (ED) with sudden onset of bilateral frontal and occipital headache, nausea, vomiting, unsteady gait, and numbness and tingling in all four extremities. A stat computed tomography (CT) scan of the brain was obtained to rule out acute subarachnoid hemorrhage, and the scan results were negative. TD was admitted to the hospital for a more thorough neurological workup because of the sudden onset of her symptoms.
On neurological examination, she was found to be in significant pain, moaning, and unable to answer detailed questions. She was mentally aware and alert; however, she appeared exhausted. According to her mother, who was at the bedside, TD had been experiencing generalized weakness and a 3-month history of "leg heaviness" for which she did not seek medical attention. Only in the past day and a half--when the headache began and increased in severity--did TD go to the ED. During the neurological examination, she was able to move her extremities distally and proximally with 4/5 power, and her deep tendon reflexes were 2+ on the left side and 3+ on the right side. Her gait was significantly abnormal with unsteady and wide-based stepping movements, which she explained was a result of the heaviness she felt in her legs. Her pupils were equal, round, and reactive bilaterally, and extraocular movements were intact. The only other significant finding was a bilateral dysmetria evidenced by grossly overshooting on the finger-to-finger test, more prominent on the right than left. Past medical history was not significant for a preceding infectious illness or recent immunizations. She denied any fevers or seizure activity. She also denied any respiratory or gastrointestinal illnesses during the past month. This was the first time the patient had ever been in a hospital. Family history was noncontributory. The patient denied smoking, drinking alcohol, or using any medication, including birth control pills. She had no known allergies and was up-to-date on all immunizations.
Magnetic resonance imaging (MRI) of the brain and spine was ordered, in addition to magnetic resonance angiography (MRA) and magnetic resonance venography (MRV). The MRA and MRV series results were negative. The MRI of the brain showed an enhancing lesion embedded in the right cerebellar hemisphere (Fig 1). The spine MRI showed extensively enhancing, multilevel, intramedullary, abnormal signals in the cervical (Fig 2) and thoracic cord seen on the T2-weighted images as well as on fluid attenuated inversion recovery (FLAIR) images. The findings prompted a neurology consult for further evaluation. The list of differential diagnoses at this point was extensive. A lumbar puncture was performed, and the cerebrospinal fluid (CSF) was sent to the laboratory for a multitude of tests to rule out conditions such as an inflammatory process, sexually transmitted diseases, Lyme disease, and West Nile virus. All of the blood work results were negative. Based on the clinical presentation and neuroimaging, the patient was diagnosed with ADEM. The patient was started on 1 gram intravenous (IV) infusion of methylprednisolone daily for 5 days. Within 1-2 days after the IV steroid infusion, she started to neurologically improve, especially in gait, and was able to ambulate without falling.
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Pathophysiology of Acute Disseminated Encephalomyelitis
ADEM is a monophasic, nonvasculitic, inflammatory, demyelinating disease that can affect the entire central nervous system (CNS). It might be indistinguishable from many forms of encephalitis except for its patchy distribution of demyelinating lesions that may have a striking similarity to lesions caused by multiple sclerosis (MS). Unlike MS, ADEM is considered a disease of singular occurrence from which most people fully recover (Rust, 2005). Because of this fact, few biopsies have been obtained, and the nature of the condition remains elusive. ADEM appears to occur most frequently after childhood infections such as measles, smallpox, chickenpox, or their respective vaccinations (Menge et al., 2005). It has also been known to occur after nonspecific upper respiratory infections. The exact mechanism of disease pathophysiology is unknown. It is thought that the CNS becomes inflamed with subsequent demyelination because of a primary autoimmune response or an immune response secondary to an infection (Menge et al.). Regardless of the cause, the clinical and radiographic presentations remain the same.
It is difficult to estimate the incidence and prevalence of ADEM. In the United States, postvaccination ADEM for the prevention of mumps, measles, and rubella and for tick-borne encephalitis occurs in 10-20 out of 100,000 individuals (Menge et al., 2005). However, in developing countries without vaccinations, ADEM after "wild-type" measles is substantially higher, occurring in 100 out of 100,000 people (Rust, 2005). There is a seasonal risk with a peak in the winter and spring; the lowest incidence occurs in July and August. Risk factors include a combination of genetics, infectious diseases, exposure to immunizations, and light skin pigmentation (Rust). The condition is found in all ethnic groups, which complicates the assessment of risk factors. ADEM occurs worldwide, although it is thought to affect more people with a lesser degree of skin pigmentation in higher latitudes, similar to MS. ADEM is more common in children, with a mean age of 7.1 years and a peak range of 3-10 years (Dale & Branson, 2005). Mortality has been estimated as high as 10%-20% (Gabis, Panasci, Andriola, & Huang, 2004), and as low as less than 2% (Rust). Morbidity usually involves visual, motor, autonomic, or intellectual deficits, and epilepsy if gray matter is affected. Deficits may persist for several weeks; however, most deficits resolve within 1 year (Rust). Mental retardation is possible, especially in children younger than 2 years of age at disease onset. Males and females are equally affected. Female adolescents with ADEM are more likely than males to develop MS in the future (Dale & Branson), though there is no strong scientific theory to explain this occurrence.
The definition of ADEM has not been well articulated in the literature, despite incidents of the disease being reported for the last 250 years. Hollinger, Sturzenegger, Mathis, Schroth, and Hess (2002) provided criteria to facilitate diagnosis, including (1) a history of recent infection, although it may have been clinically silent; (2) a monophasic disease course; (3) disseminated CNS disease with neurologic findings; and (4) the absence of metabolic or infectious disorders. The history of events is the single most important part of the diagnostic criteria. In many cases--especially in the absence of a prodromal illness or recent vaccination--ADEM is a diagnosis of exclusion. The patient most commonly presents with one or more of the following symptoms: fever, headaches, meningismus, visual or mental status disturbances, or irritability. The signs and symptoms vary widely in each case. If there is cerebellar or spinal cord involvement, the patient may present with ataxia, nystagmus, sensory dysfunction, or weakness (Rust, 2005).
Neither MRI nor CSF results alone are adequate for diagnosing ADEM. MRI is useful in highlighting the disseminated involvement of white matter and identifying extent and location. MRI findings are virtually impossible to distinguish from MS lesions (Petzold, Stiepani, Klingebiel, & Zschenderlein, 2005), as both MS and ADEM may show T2-weighted images and FLAIR signal abnormality as well as abnormal enhancement with gadolinium contrast. However, T2-weighted images show ADEM lesions that are more pronounced with poorly defined margins in deep white matter and periventricular sparing. If the spinal cord is involved it will show large, swollen lesions that may extend into the thoracic region from the cervical region (Dale & Branson, 2005). As a general rule, ADEM lesions in the spinal cord are continuous lesions affecting multiple levels, whereas a typical MS lesion is confined to one spinal cord level. Any single lesion affecting more than one spinal level should raise suspicion for ADEM in the appropriate clinical picture. The typical MS lesions are also posterior in location on axial, cross-sectional views of the spinal cord, whereas the ADEM lesions tend to be more diffusely present throughout the entire cord. Unfortunately, many disorders can affect the CNS white matter, including vascular, metabolic, infectious, and inflammatory processes. MRI is helpful in ruling out other disorders but is not specifically diagnostic of ADEM.
Analysis of CSF is another important diagnostic tool in differentiating many neurologic conditions. In regard to ADEM, the CSF can be normal or, more likely, show nonspecific changes including an elevated protein and pleocytosis with lymphocytic predominance, a normal glucose, and negative cultures (Kennedy, 2004). Still, evaluation of CSF remains an essential element of the workup to rule out other possible causes, such as Lyme disease or other infectious diseases. Electroencephalogram (EEG) also is often performed, eliciting abnormal, yet nonspecific results including generalized and focal slowing and epileptiform discharges. Hollinger et al. (2002) found that EEG was abnormal in seven of eight patients with ADEM in which it was performed.
Because the list of differential diagnoses is extensive, history is vital in establishing the diagnosis. Figure 3 is by no means exhaustive, yet it constitutes a working menu of possibilities that should be considered early on in the differential.
Fig 3. ADEM Differential Diagnoses Multiple sclerosis Guillain-Barre syndrome Stroke Meningitis Lymphoma Acute inflammatory demyelinating polyradiculoneuropathy Toxic/metabolic encephalopathy Infectious encephalitis Vasculitis Postmalarial neurological syndrome HIV-1 central nervous system complications Metastatic tumor Glioblastoma multiforme Antiphospholipid antibody syndrome Neurosarcoidosis Cavernous sinus syndromes Cerebral venous sinus thrombosis Neurosyphilis Systemic lupus erythematous Wegener granulomatosis Note. ADEM = acute disseminated encephalomyelitis. Information from "Acute Disseminated Encephalomyelitis," by R. K. Garg, 2003, Postgraduate Medicine Journal 79, pp. 11-17; "Postinfectious Encephalomyelitis," by C. Mihai and B. Jublet, 2005, Current Neurolology and Neuroscience Reports, 5, pp. 440-445; and "Acute Disseminated Encephalomyelitis: An Update" by T. Menge, B. Hemmer, S. Nessler, H. Wiendl, O. Neuhaus, H. Hartung, et al., 2006, Archives of Nteurology, 62, pp.1673-1680.
There is a close diagnostic association between MS and ADEM that is difficult to differentiate on the basis of a single clinical encounter or radiographic image. Prompt diagnosis is warranted because treatment and healthcare decisions associated with each condition differ. It is not entirely clear in the literature if ADEM and MS are distinct clinical disorders, in that they share many similar attributes, such as being a disseminated disease of the CNS and radiographically similar. Because of the nature of the variability of disseminated disease, presentation of either condition can easily mimic the other; however, ADEM tends to have neurologic signs and symptoms not typically present in MS, such as headache, nausea, vomiting, drowsiness, and meningismus.
It is also important to differentiate between ADEM and viral encephalitis. Like MS, this distinction is not always apparent. The striking feature of ADEM is the prodromal illness or history of recent vaccination that is uncommonly found in encephalitis. ADEM may also be associated with visual loss in one or both eyes and spinal cord involvement; these problems are also uncommon in encephalitis (Kennedy, 2004). A history of recent travel abroad or to areas of high risk for arboviruses in the U.S. is useful information for the diagnosis of encephalitis. Because of the multiple nuances among ADEM and similar conditions, the necessity of a detailed and careful history of events cannot be overemphasized.
The overall goal of treatment is to arrest the CNS inflammatory response as quickly as possible. High-dose corticosteroids are the treatment of choice in inflammatory, demyelinating CNS diseases. Methylprednisolone 10-30 mg/kg/d (maximum 1 gram per day) over 3-5 days (Dale & Branson, 2005; Menge et al., 2005; Rust, 2005), followed by a tapered oral prednisolone over 2-6 weeks (Dale & Branson), is recommended as a standard medical treatment. Other options include the use of antiinflammatory and immunosuppressive treatments such as IV immunoglobulin (IVIG) and plasmapheresis (PE). While corticosteroids remain the first line of therapy, there have been no randomized controlled trials to determine the best evidence for medical treatment. PE and IVIG have both been used successfully in the treatment of ADEM; however, use tends to be reserved for cases where there is a contraindication or resistance to steroids or in the case of treatment failure (i.e., when no improvement is seen or the patient continues to deteriorate; Garg, 2003; Mihai & Jubelt, 2005). There are no formal guidelines to specify when treatment failure or resistance to therapy occurs; this distinction is based on the neurologist's experience with demyelinating disease and the overall impression of the patient's condition based on that knowledge.
The usual prognosis is excellent for most patients diagnosed with ADEM; however, mortality rates continue to be reported as high as 10% (Rust, 2005). Favorable outcomes were reported in 70%-90% of patients with ADEM (Menge et al., 2005), with 57%-81% making a complete recovery (Dale & Branson, 2005). Degree of recovery was not found to be related to the severity of the illness; even children who developed quadriparesis or blindness or went into a coma were able to recover fully (Rust). Relapses after ADEM are uncommon. When the disease does recur, healthcare providers are encouraged to reconsider the possibility of the relapsing-remitting type of MS. Rust reported the development of MS in 25% of patients with ADEM. The highest risk for MS was seen in patients who lacked one or more of the following characteristics: fever, mental status changes, history of prodromal viral illness or history of recent vaccination, EEG slowing, and significant CSF immune profile. Garg (2003) found that all the patients in his study that developed MS did so within 1 year of the initial ADEM episode.
TD remained in the hospital for 2 weeks. Once the diagnosis was made--several days after admission-she received high-dose steroids for 5 days. The steroid therapy was effective for TD, but not everyone is as fortunate. Although uncommon, patients can deteriorate further, despite therapy. TD continted on oral steroids, which were tapered over the course of a month. While there was marked improvement, she still required physical therapy and minimal assistance with walking, for which she underwent inpatient rehabilitation for several weeks. The nurses informed TD that a full recovery could take up to a year or longer. Because of TD's age, gender, and presentation, she is at an increased risk for the development of MS in the future; however, there are no known predictors or risk factors to suggest that she is at high risk. There are no specific activity restrictions for patients following ADEM, except for limitations that are imposed by focal neurologic deficits, loss of vision, ataxia, paresis, or other complications. Pain associated with ADEM is generally similar to neuropathic pain and is treated with centrally acting drugs such as carbamazepine, gabapentin, or topiramate. Fortunately, TD did not have associated pain. Teaching should include information about potential side effects of steroid therapy including, but not limited to, steroid-induced gastritis and stress ulcers, as well as hyperglycemia. TD planned to follow up in 6 months with an MRI scan to assess if the lesions had completely disappeared. In the meantime, she began to recover with the help of her family and friends who have been continuously at her side.
ADEM is a monophasic, inflammatory, demyelinating CNS disease that, once treated, has an excellent prognosis for recovery. TD, a 22-year-old female suffering from her first bout of ADEM, began recovering within several days after starting high-dose corticosteroids. ADEM is a neurologic condition that must be rapidly identified to reduce the extent of injury to the CNS. Because of the extensive range of differential diagnoses, the patient's history is the most important aspect of the examination. Nurses are in a position to provide essential information in collaboration with the neurology team by asking pertinent questions and performing a comprehensive assessment. Nurses also need to be familiar with the clinical course and prognosis of ADEM to help facilitate patient and family coping through the disease process.
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Dale, R. C., & Branson, J. A. (2005). Acute disseminated encephalomyelitis or multiple sclerosis: Can the initial presentation help in establishing a correct diagnosis? Archives of Disease in Childhood, 90(6), 636-639.
Gabis, L. V., Panasci, D. J., Andriola, M. R., & Huang, W. (2004). Acute disseminated encephalomyelitis: An MRI/MRS longitudinal study. Pediatric Neurology, 30(5), 324-329.
Garg, R. K. (2003). Acute disseminated encephalomyelitis. Postgraduate Medical Journal, 79, 11-17.
Hollinger, P., Sturzenegger, M., Mathis, J., Schroth, G., & Hess, C. W. (2002). Acute disseminated encephalomyelitis in adults: A reappraisal of clinical, CSF, EEG, and MRI findings. Journal of Neurology, 249(3), 320-329.
Kennedy, P. G. E. (2004). Viral encephalitis: Causes, differential diagnosis and management. Journal of Neurology, Neurosurgery & Psychiatry, 75, 10-15.
Menge, T., Hemmer, B., Nessler, S., Wiendl, H., Neuhaus, O., Hartung, H. P., et al. (2005). Acute disseminated encephalomyelitis: An update. Archives of Neurology, 62(11), 1673-1680.
Mihai, C., & Jubelt, B. (2005). Post-infectious encephalomyelitis. Current Neurology and Neuroscience Reports, 5(6), 440-445.
Petzold, G. C., Stiepani, H., Klingebiel, R., & Zschenderlein, R. (2005). Diffusion-weighted magnetic resonance imaging of acute disseminated encephalomyelitis. European Journal of Neurology, 12(9), 735-736.
Rust, R. S. (2005). Acute disseminated encephalomyelitis. Retrieved May 4, 2007, from www.emedicine.com/neuro/topic500.htm.
Kiwon Lee, MD, is clinical director of Neuro ICU at Jefferson Hospital for Neuroscience--Thomas Jefferson University Hospital, Philadelphia, PA.
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|Author:||Harris, Catherine; Lee Kiwon|
|Publication:||Journal of Neuroscience Nursing|
|Article Type:||Case study|
|Date:||Aug 1, 2007|
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