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Multiple Sclerosis 9/20/13

posted Sep 20, 2013, 12:50 PM by Eliany Mejia   [ updated Sep 20, 2013, 3:02 PM ]

Today we talked about a very interesting case with typical presentation of Multiple sclerosis, so lets talk about it!

Multiple sclerosis (MS) also known as encephalomyelitis disseminate and is characterized by chronic inflammation with demyelination and scarring. 
MS is the most frequent cause of neurologic disability in early to middle adulthood aside from trauma. It is more common in females. The median and mean ages of MS onset are 23.5 and 30 years of age, respectively. The peak age of onset is about 5 years earlier for women than for men. Onset of MS can rarely occur as late as the seventh decade. 

MS derived its term from the multiple scarred areas in the brain termed plaques. The acute lesion in MS is characterized by perivenular cuffing and tissue infiltration by mononuclear cells predominantly T lymphocytes and macrophages. As the lesion evolves, demyelination occurs, with macrophages and microglial cells scavenging the myelin debris. Proliferation of astrocytes lead to scar formation. MS is more common in people who live farther from the Equador. The cause of this geographical pattern is not clear. While the north-south gradient of incidence is decreasing, as of 2010 it is still present. 

While the cause is not clear, the underlying mechanism is thought to be either destruction of the immune system or failure of the myelin-producing cells. Proposed causes for this include genetics and environmental factors such as infections. There is no association between vaccines and MS. Although many viruses, and particularly the Epstein Barr virus, have been associated with MS, there is no specific evidence linking viruses directly to the development of MS. Genetic factors appear to contribute to the pathogenesis of MS, particularly variation involving the HLA-DRB1 locus and HLA-DR2 allele. 

Clinical presentation:
The most common initial symptoms include weakness in one or more limbs, blurring of vision secondary to optic neuritis, sensory disturbances, diplopia and ataxia. 
MS takes several forms, with new symptoms either occurring in isolated attacks (relapsing forms) or building up over time (progressive forms). Between attacks, symptoms may go away completely; however, permanent neurological problems often occur, especially as the disease advances. 

Clinical course:

Several subtypes, or patterns of progression, have been described. Subtypes use the past course of the disease in an attempt to predict the future course. They are important not only for prognosis but also for treatment decisions. The National Multiple Sclerosis Society, in 1996 described 4 clinical courses:

1. Relapsing remitting (RRMS) : characterized by unpredictable relapses followed by periods of months to years of remission. This describes the initial course of 80%- 85% of individuals with MS. When deficits always resolve between attacks, this is sometimes referred to as benign MS. However, most patients with RRMS will eventually enter a secondary progressive phase.
2. Secondary progressive (SPMS): occurs in around 65% of those with initial relapsing-remitting MS, who eventually have progressive neurologic decline between acute attacks without any definite periods of remission. 
3. Primary progressive (PPMS): occurs in approximately 10–20% of individuals, with no remission after the initial symptoms. It is characterized by progression of disability from onset, with no, or only occasional and minor, remissions and improvements.
4. Progressive relapsing (PRMS): describes those pts who, from onset, have a steady neurologic decline but also have clear superimposed attacks. This is the least common of all subtypes. 

The relapsing form of MS is generally associated with a better prognosis than progressive disease, other prognostic factor are lesion load and psycho-social stress.

Clinical data alone may be sufficient for a diagnosis of MS if an individual has had separate episodes of neurologic symptoms characteristic of the disease. In those who seek medical attention after only one attack, other testing is needed for the diagnosis. The most commonly used diagnostic tools are neruoimaging, analysis of CSF and evoked potentials.

The Poser criteria for the diagnosis of MS were developed in the mid 80's and considered clinical characteristics and a number of laboratory studies including CSF analysis, evoked potentials, and neuroimaging. ( see attachment). The Poser criteria were developed primarily to ensure that only MS patients were included in research studies. They have been supplanted by the McDonald criteria, which were developed in 2001 and subsequently revised in 2005 and 2010.

McDonald criteria: The core requirement of the diagnosis is the objective demonstration of dissemination of CNS lesions in both space and time, based upon either clinical findings alone or a combination of clinical and MRI findings: 
Dissemination in space is demonstrated on MRI by one or more T2 lesions in at least two of four MS-typical regions of the CNS (periventricular, juxtacortical, infratentorial, or spinal cord) or by the development of a further clinical attack implicating a different CNS site. 
- Dissemination in time is demonstrated on MRI by the simultaneous presence of asymptomatic gadolinium-enhancing and nonenhancing lesions at any time, or a new T2 and/or gadolinium-enhancing lesion(s) on follow-up MRI, irrespective of its timing with reference to a baseline scan, or by the development of a second clinical attack. 

The McDonald criteria assign diagnostic confidence as follows:

- The diagnosis of "MS" is given if the criteria are fulfilled and there is no better explanation for the clinical presentation
- The diagnosis of "possible MS" is given if MS is suspected but the criteria are not completely met 
- The diagnosis of "not MS" is given if another diagnosis better explains the clinical presentation 

Testing of CSF can provide evidence of chronic inflammation in the CNS. CSF abnormalities consist of mononuclear cell pleocytosis, an elevation in the level of total Ig, and the presence of oligoclonal Ig, which are inflammation markers found in 75–85% of people with MS. Evoked response testing may detect slowed or abnormal conduction in visual, auditory, somatosensory, or motor pathways ( usually abnormal in 67-85% of pts with MS). However, no clinical sign or diagnostic test finding is unique for MS. 

The treatment may be for symptomatic management, or focused to arrest the disease with chemotherapeutic drugs, depending on the pattern of MS. During acute attacks, administration of high doses of corticosteroids, such as methylprednisolone, is the usual therapy, with oral corticosteroids seeming to have a similar efficacy and safety profile. Although generally effective in the short term for relieving symptoms, corticosteroid treatments do not appear to have a significant impact on long-term recovery. Severe attacks which do not respond to corticosteroids might be treatable by plasmapheresis

Disease-modifying treatments

After making a diagnosis of definite MS, it is important to present the data in summary form to the patient and to discuss the risks and benefits of each treatment. One of the most important points is to remind the patient that these therapies slow the disease, but they do not stop it or make the patient feel better.

Eight disease-modifying agents have been approved for RRMS including:Interferon beta-1a, Interferon beta-1b, glatiramer acetate, mitoxantrone, natalizumab, fingolimod, teriflunomide and dimethyl fumarate.  Their cost effectiveness as of 2012 is unclear. There are no consensus guidelines, with the exception that mitoxantrone should be reserved for patients with rapidly advancing disease who have failed other therapies

Treatment for progressive MS should be individualized on the basis of disease progression as well as patient and physician preference. Treatment recommendations differ between PPMS and SPMS. And all suggested treatments for PPMS are empiric, as no convincing clinical trial evidence of effectiveness has been found for disease modifying therapy.

Our patient has the typical presentation of RRMS, this is her MRI:
MRI brain: 1.7 cm abnormal area of enhancement in the left centrum semi-ovale consistent with an active area of demyelination.  There was also nonenhancing periventricular and subcortical white matter demyelinating disease. Findings were consistent with MS. Our patient was started on IV steroids with almost complete resolution of her symptoms. She is having regular follow up with Neurology who is planning to start DMTs. 

I have also attached some good review articles for you to read, including the new and revised 2010 McDonald diagnostic criteria. Enjoy the reading and have a great weekend!!
Eliany Mejia,
Sep 20, 2013, 2:27 PM
Eliany Mejia,
Sep 20, 2013, 2:27 PM