Multiple Sclerosis

Question 1

What are 4 details about multiple sclerosis?

Answer 1

Multiple Sclerosis is an autoimmune inflammatory disease in which the myelin sheaths surrounding the axons of neurons (nerve cells) are damaged or destroyed, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms

The name multiple sclerosis refers to scars (scleroses)
particularly in the white matter of the brain and spinal
cord

Disease onset usually occurs in young adults between the ages of 20 and 40 years

Multiple sclerosis is diagnosed roughly twice as often in women compared to men

Question 2

What are 6 details about the course of multiple sclerosis?

Answer 2

Multiple sclerosis is a complex debilitating condition with high morbidity and mortality

Often the disease follows a biphasic course where a relapsing-remitting stage is followed by a more severe progressive stage

Onset of these attacks can include paresthesia (numbness), diplopia (double vision), scotoma (visual anomalies), sensory and motor disorders of limbs and cerebellar incoordination (lack of balance).

After a variable amount of time (months to years), the
relapsing-remitting stage of multiple sclerosis may advance to an episodic downhill course of progressively worse symptoms culminated by blindness due to retrobulbar neuritis, ataxia, incontinence, paraplegia, major system failure and death

Progressive disease is untreatable and the main cause of permanent disability in the multiple sclerosis patient population

There is no cure for multiple sclerosis and despite intensive efforts, the average life expectancy is reduced by about 10 years compared to the general population

Question 3

What are 3 details about the global burden of multiple sclerosis?

Answer 3

Based upon a global survey conducted by WHO during 2005-2007, there are more than 1.3 million people with multiple sclerosis, 630,000 in Europe, 520,000 in the Americas, 66,000 in the Eastern Mediterranean, 56,000 in the Western Pacific, 31,500 in Southeast Asia
and 11,000 in Africa

During 2015, GBD investigators estimated that 2.0 million people were living with multiple sclerosis in the world population

Nevertheless, the age-standardized annual prevalence decreased by 2% during 2005-2015

Question 4

What are 7 details about the prevalence and incidence of multiple sclerosis in region?

Answer 4

Globally, the annual prevalence of multiple sclerosis is extraordinarily variable, ranging from less than 1 case per 100,000 in Africa to 176 cases per 100,000 in
Hungary

The median prevalence is 30 per 100,000.
Rates exceed 100 cases per 100,000 in North America (USA, Canada) and several European countries (Hungary, Germany, Czech Republic, Norway, Denmark,
Poland)

Far lower rates (less than 10 cases per 100,000) are reported by most countries in Africa, Southeast Asia, the Western Pacific and South America

Prevalence rates are substantially higher in high income countries than low income countries

The median annual incidence among all reporting countries is 25 cases per million with a range from less than l in Africa to 290 cases per million in the small Eastern Mediterranean nation of Croatia

The global pattern of incidence is similar to the prevalence

High rates are found in high income developed countries and low rates in low income developing countries

Question 5

What are 3 details about the annual age-specific incidence of multiple sclerosis?

Answer 5

Despite the wide international variability in the prevalence and incidence rates, certain epidemiologic features of multiple sclerosis have been found to be
relatively invariant

The majority of cases (60-70%) are diagnosed prior to age 40 years and the mean age of onset is 29 years for all regions and income groups in both men and
women

There is a consistent 2:1 female to male ratio of both the incidence and prevalence of multiple sclerosis, irrespective of income level

Question 6

What are 2 details about the global DALY for multiple sclerosis?

Answer 6

As with the global patterns of prevalence and incidence, the DALY rates are higher in developed nations with more advanced diagnostic, treatment and reporting capabilities

High annual DALY rates are found in high income developed countries and low rates in low income developing countries

Question 7

What are 8 details about lymphocyte penetration of blood-brain barrier?

Answer 7

Disruption of the blood brain barrier precedes the development of multiple sclerosis

The blood brain barrier consists of tight junctions between the endothelial cells that line the capillaries and other blood vessels of the brain and spinal cord

Under normal conditions, these tight junctions prevent entrance of T cells into neurological tissues

Many viruses and certain other infectious agents may compromise the blood-brain barrier and allow T cells to pass through

Upon clearance of the infection, the T cells may become trapped inside the brain and stimulate immunoreactivity and inflammation

Dysregulation of the blood-brain barrier and transendothelial migration of activated leukocytes and their release of inflammatory cytokines and chemokines
are among the earliest cerebrovascular abnormalities seen in multiple sclerosis brains

Inflammation is a chief pathologic hallmark of relapsing-remitting multiple sclerosis

According to one model, T cells gain entrance into the brain through the blood-brain barrier and become immunoreactive, thereby stimulating a cascade of destructive inflammatory processes including axon transection, myelin degradation and glial cell death

Question 8

What are 5 details about demyelination and multiple sclerosis?

Answer 8

Imaging the lesions using MRI with gadolinium
enhancement provides the most conclusive evidence for a diagnosis of relapsing-remitting multiple sclerosis

Lesions can be pathologically characterized as
immunologically active or chronic by various degrees of
microgliosis, astrocytosis, myelin vacuolation or loss

Demyelinated lesions will undergo a reparative process
whereby oligodendrocytes replace lost myelin with a
thinner but still functional sheath.

The principal cell responsible for myelin formation and repair is the oligodendrocyte, a glial cell that synthesizes and maintains myelin for up to 40 nerve axons in the central nervous system.

Failure of remyelination by oligodendrocytes is thought to be largely responsible for sustained neurological symptoms in patients with progressive multiple
sclerosis

Question 9

What are 2 details about multiple sclerosis and ethnic differences?

Answer 9

The highest rates of multiple sclerosis are observed
in regions largely inhabited by Caucasians and the
lowest in those areas with primarily non-Caucasian
populations

Environmental agents also predominantly influence
the risk, irrespective of race

Question 10

What are 2 details about the genetics of multiple sclerosis?

Answer 10

Genetic variation at the Major Histocompatibility Complex (MHC) on chromosome 6 has been found to
influence the risk of developing multiple sclerosis

Several genetic polymorphisms of the human leukocyte
antigen (HLA) system appear to either increase or decrease the risk

Question 11

What are 2 details about multiple sclerosis and Sardinia?

Answer 11

Prevalence rates of multiple sclerosis in Sardinians
are among the highest in the world, ranging from 144
to 152 per 100,000.

The genetically isolated population of this small
island also has one of the highest rates of type 1
diabetes, another autoimmune conditions

Question 12

What are 4 details about multiple sclerosis, sunlight, and vitamin D?

Answer 12

Evidence from both in vitro investigations and animal
studies suggests that vitamin D influences the risk of
developing multiple sclerosis

In animal studies, the administration of biologically active vitamin D has been shown to prevent the onset of
experimental autoimmune encephalitis (an experimental mouse model of multiple sclerosis) as well as its progression

In humans, the totality of observational evidence suggests that vitamin D may have both chemopreventive and therapeutic value in reducing the burden of multiple sclerosis

Multicenter double-blind placebo-controlled randomized clinical trials of vitamin D supplementation are currently in progress to elucidate such effects in patients with multiple sclerosis

Question 13

What are 6 details about infectious disease and multiple sclerosis?

Answer 13

Scores of microbial infectious agents have been proposed as potential triggers in the pathogenesis of multiple sclerosis; however, no specific microbe (MMR, HHV etc) has been clearly substantiated as causative

Many childhood infections have been studied including measles, mumps, rubella, varicella, human herpes virus type 6, retroviruses, and Chlamydia pneumoniae

Albeit, results for specific microbes either reflect no association whatever or are inconsistent from study to study

One possible exception is Epstein-Barr Virus (EBV) which infects up to 90% of the population by adulthood

Several serological studies have detected significantly higher frequencies of EBV antibodies in the sera and cerebral spinal fluid of multiple sclerosis patients
compared to controls

Some studies have found an increased risk among individuals with a history of infectious mononucleosis (which is caused by EBV infection)

Question 14

What are 2 details about multiple sclerosis and migrant populations?

Answer 14

Studies of multiple sclerosis rates in migrants show that
people migrating from a high risk area to a low risk area
experience a decrease in disease rates, whereas people
migrating from a low risk area to a high risk area retain
their low rates

These findings suggest that the risk of disease is established during early in life and prior to the time of migration

Question 15

What are 4 details about multiple sclerosis and organic solvents?

Answer 15

Several studies have assessed the association between exposure to organic solvents and multiple sclerosis

A meta-analysis of case control studies found a 70% increase in overall risk (pooled OR=1.7)

However, a subsequent review of 14 studies revealed
inconsistencies and methodological issues with risk estimates ranging from 0.4 to 4.9

Additional studies are needed to confirm a positive association

Question 16

What are 2 details about multiple sclerosis and tobacco?

Answer 16

A meta-analysis revealed an approximate 50% increase in the risk for smokers compared to nonsmokers (RR=1.52).

Findings suggest that smoking significantly heightens the risk of developing multiple sclerosis

Question 17

What are 6 details about the prevention and therapy of multiple sclerosis?

Answer 17

There is no known cure for multiple sclerosis.

Corticosteroids are typically used to manage acute attacks and certain immunomodulatory drugs (interferon-b, glatiramer acetate) have proven effective in some patients

A variety of monoclonal antibodies that target specific
molecules in the immunopathogenesis of multiple sclerosis are currently being investigated in randomized clinical trials

Therapies aimed at enhancing natural mechanisms of
remyelination in the brain hold promise for the treatment of progressive multiple sclerosis and are of intense interest in current neurological research

There is intense interest in the use of supplementary vitamin D or vitamin D analogs for the prevention and management of multiple sclerosis

Randomized clinical trials are currently in progress to evaluate the potential benefit of vitamin D therapy for patients with relapsing-remitting multiple sclerosis