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Multiple Sclerosis

Multiple sclerosis is an acquired chronic immune mediated inflammatory condition
 of the central nervous system ( CNS ) , affecting both the brain and 
the spinal cord ( NICE 2015 ).

Relapsing-remitting
 MS ( RRMS )-Most common subtype 
( 80 to 90 % ) where periods of stability ( remission ) are followed by episodes when there are exacerbation of symptoms ( relapses )

CNS repair and use of neurological reserves can remodel and compensate the damage to some extent.

Secondary progressive –About 2/3 rd of people who start with RRMS may progress to secondary progressive when there is a gradual accumulation of disability unrelated to relapses , which become less frequent or stop completely.

Primary Progressive –About 10 % of people have primary progressive MS where symptoms gradually develop and worsen over time from the start , without ever experiencing relapses and remissions.

Underlying neurodegeneration rather than inflammation as in RRMS is the cause.

How common ? Multiple sclerosis ( MS ) is the commonest non-traumatic disabling disease to affect young adults MS is increasingly becoming a global disease – about 2.5 million individuals are affected worldwide MS is more common in females with a ratio of 3 : 1 in most developed countries Prevalence of MS varies with latitude Mean age at symptom onset and diagnosis is the mid 30s.

Pathophysiology-Exact pathophysiology is not known What is known is that the disease is mediated by auto-reactive lymphocytes that cross the blood-brain barrier – enter the CNS and cause local inflammation resulting in demyelination and axonal loss The resulting inflammation , damage and destruction is generally irreversible and leads to brain atrophy and a host of symptoms including reduced fine motor control , cognitive impairment , depression and anxiety.

Risk factors –Female sex Northern latitude- prevalence increases as the distance from the equator increases Genetic- multiple genes are though to contribute 
Family history of auto-immnune illness
About 1 in 8 patients have a family h/o MS Smoking Vitamin D deficiency- vit D sufficiency is a major protective factor on which there is consensus and has known interactions with many factors affecting MS onset / severity Epstein Barr virus ( EBV )

Presentation –Diagnosis of MS is to be made by a consultant neurologist 
who may use an established up to date criteria for eg the 2010 McDonald criteria. 

Clinical presentation in MS may include
 loss or reduction of vision in 1 eye with painful eye movements double vision ascending sensory disturbance and / or weakness problems with balance , unsteadiness or clumsiness altered sensation traveling down the back and sometimes into the limbs when bending the neck forwards
( Lhermitte’s symptom )

these may happen
 usually in people who are under 50 and may have a h/o previous neurological symptoms and have symptoms that have evolved over more than 24 hrs and have symptoms that may persist over several days or weeks and then improve.

Patients may present with Clinically Isolated Syndromes ( CIS ) – can be mono or polysymptomatic based on the location of the eloquent lesions. The most commonly seen presentations are optic neuritis , brain and spinal cord syndromes .
Some studies quote specific figures as ( this for RMMS ) – the 1st relapse usually consists of optic neuritis ( 20-30 % ) , acute myelitis (20-50 % ) or brainstem lesions (10-15 % )


 Optic neuritis – in about 20 % of patients acute demyelinating optic neuritis is the presenting symptom About 1/2 of MS patients would be affected by acute demyelinating optic neuritis at some point of the illness Blurry spots in the visual feild Transverse myelitis -impairment of motor , sensory tracts in the spinal cord due to inflammatory mediated injury
TM may manifest as tightening around the chest or abdomen which indicates TM of the posterior columns of the spinal cord Brainstem involvement may manifest as
double vision , vertigo , facial weakness or bulbar symptoms as dysphagia Weakness -is common. Corticospinal tract involvement usually leads to focal weakness of the lower extremities Numbness and paraesthesia Sensory problems -pain ( burning or electrical ) and different unpleasant feelings Cerebellar dysfunction – tremor , dysmetria , dysdiadochokinesia , gait ataxia Fatigue- affects most MS patients Cognitive deficits – memory impairment , major depression Heat insensitivity Headaches.

Diagnosis -A delay in diagnosis is common.
MS is a clinical diagnosis – supported by MRI findings , CSF analysis , laboratory findings , visual evoked potential studies. No single test is totally reliable hence diagnosis is made based on clinical features supported by findings from certain studies.

NICE has advised that the following blood tests should be done before referring a person suspected of having MS Full blood count Inflammatory markers ( e.g ESR , CRP ) Liver function tests Renal function tests Calcium Glucose Thyroid function tests Vit B12 HIV serology.

Principles of treatment –Early diagnosis and initiating of treatment is the key Over a quarter of patients with symptom of MS have to visit their family doctor over 4 times before they are referred to a neurologist Making a diagnosis of MS is one of the most challenging aspects of practicing neurological medicine A delay of about 10 yrs before the diagnosis was common but this is now improving with more refined diagnostic criteria and imaging techniques Delayed diagnosis is the biggest barrier to treatment across the globe Various other diagnoses and disease processes can confuse the clinician – together these are called MS mimics- a discussion is not possible here about those but a good link is provided under resources from National MS Society – Other conditions to rule out The neurological reserve and repair mechanisms are limited and if MS related brain damage is undetected MS may go untreated leading to exhaustion of brain reserves and an early progression to SPMS state ie

Early treatment is to prevent further damage and preserve function
 Early diagnosis ensures

early pharmacological treatment

steps to improve brain health as exercise , smoking cessation , weight loss and control of co-morbidities such as hypertension
 MS lead to irreversible damage to the brain and spinal cord and once neurological reserve is exhausted there are steady increases in physical and mental disability – at this stage pharmacological management fails and there are no approved drug treatments for non-relapsing secondary progressive MS
.

Relapse –Diagnose a relapse of MS if the person
 develop new symptoms or has worsening of existing symptoms


and these last for more than 24 hrs in the absence of infection or any other cause after a stable period of atleast 1 month

Also take into account before diagnosing a relapse
 r/o any infection – particularly UTIs and respiratory infections and try and differentiate if this is a relapse or fluctuation in disease or progression

Assess and offer treatment as early as possible and within 14 days of onset of symptoms

Do not routinely diagnose a relapse of MS if symptoms are present for > than 3 months


.

Offer methylprednisolone 0.5 mg x 5 days Do not prescribe steroids at a lower doses than methylprednisolone 0.5 g daily for 5 days to treat a relapse Do not give rescue to self-administer for future relapses IV methlprednisolone @ 1 g daily x 3-5 days is an alternative – discuss with the MS team.To prognosticate effectively for MS patients is difficult There is considerable interpatient variability It is quoted in several papers that the median survival time is approximately 5-10 yrs shorter for MS patients for the age matched general population.

LINKS AND RESOURCES

FURTHER INFORMATION AND RESOURCES

Other conditions to rule out National Multiple Sclerosis Society https://www.nationalmssociety.org/Symptoms-Diagnosis/Other-Conditions-to-Rule-Out

MS trust Professional resources https://www.mstrust.org.uk/health-professionals/resources/clinical-learning/practical-guides-and-useful-links

MS treatment summary from National MS Society https://www.nationalmssociety.org/Treating-MS/Medications

MS Guidelines

American Academy of Neurologyhttps://www.aan.com/Guidelines/home/ByTopic?topicId=18

Comprehensive Care in Multiple Sclerosis https://cdn.ymaws.com/www.mscare.org/resource/collection/4CB3E940-0D5C-4ADD-9C48-8FA7AAAC2DB9/CMSC_WhitePaper_Comprehensive_Care_in_MS.pdf

The consortium of MS Centres https://www.mscare.org/page/practice_guidelines

NICE guideline https://www.nice.org.uk/guidance/cg186/documents/multiple-sclerosis-2014-full-guideline2

References-

  1. BMJ Best Practice Multiple Sclerosis Multiple Sclerosis
  2. Diagnosis Management and prognosis by Benjamin K-T Tsang in Australian Family Physician Vol 40 , No 12 , December 2011
  3. Multiple Sclerosis a Primary Care Approach Am Fam Physician: 2014 Nov 1;90 (9) : 644-652
  4. Multiple Sclerosis Diagnosis and Management:A simple Literature Review Yazeed Hamoud Multaq Alshammari et al 2019 Archives of Pharmacy Practice
  5. Multiple Sclerosis Dorothee Chabas and Bertrand Fontaine et al December 2004
  6. Multiple Sclerosis in adults: management NICE Clinical Guidelines October 2014
  7. London School of Economics and Political Science Changing paradigms in the management of Multiple Sclerosis White Paper Panos Kanavos

 

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