Wednesday, May 29, 2013

Antimicrobial resistance

Antimicrobial resistance

Fact sheet N°194
Reviewed March 2012

Key facts

  • Infections caused by resistant microorganisms often fail to respond to conventional treatment, resulting in prolonged illness and greater risk of death.
  • About 440 000 new cases of multidrug-resistant tuberculosis (MDR-TB) emerge annually, causing at least 150 000 deaths.
  • Resistance to earlier generation antimalarial medicines such as chloroquine and sulfadoxine-pyrimethamine is widespread in most malaria-endemic countries.
  • A high percentage of hospital-acquired infections are caused by highly resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA).
  • Inappropriate and irrational use of antimicrobial medicines provides favourable conditions for resistant microorganisms to emerge, spread and persist.

What is antimicrobial resistance?

Antimicrobial resistance (AMR) is resistance of a microorganism to an antimicrobial medicine to which it was previously sensitive. Resistant organisms (they include bacteria, viruses and some parasites) are able to withstand attack by antimicrobial medicines, such as antibiotics, antivirals, and antimalarials, so that standard treatments become ineffective and infections persist and may spread to others. AMR is a consequence of the use, particularly the misuse, of antimicrobial medicines and develops when a microorganism mutates or acquires a resistance gene.

Why is antimicrobial resistance a global concern?

AMR kills
Infections caused by resistant microorganisms often fail to respond to the standard treatment, resulting in prolonged illness and greater risk of death.
AMR hampers the control of infectious diseases
AMR reduces the effectiveness of treatment because patients remain infectious for longer, thus potentially spreading resistant microorganisms to others.
AMR threatens a return to the pre-antibiotic era
Many infectious diseases risk becoming uncontrollable and could derail the progress made towards reaching the targets of the health-related United Nations Millennium Development Goals set for 2015.
AMR increases the costs of health care
When infections become resistant to first-line medicines, more expensive therapies must be used. The longer duration of illness and treatment, often in hospitals, increases health-care costs and the financial burden to families and societies.
AMR jeopardizes health-care gains to society
The achievements of modern medicine are put at risk by AMR. Without effective antimicrobials for care and prevention of infections, the success of treatments such as organ transplantation, cancer chemotherapy and major surgery would be compromised.
AMR threatens health security, and damages trade and economies
The growth of global trade and travel allows resistant microorganisms to be spread rapidly to distant countries and continents.

Facts on antimicrobial resistance

About 440 000 new cases of multidrug-resistant tuberculosis (MDR-TB) emerge annually, causing at least 150 000 deaths. Extensively drug-resistant tuberculosis (XDR-TB) has been reported in 64 countries to date.
Percentage of MDR-TB among new TB cases since 1994
Resistance to earlier generation antimalarial medicines such as chloroquine and sulfadoxine-pyrimethamine is widespread in most malaria-endemic countries. Falciparum malaria parasites resistant to artemisinins are emerging in South-East Asia; infections show delayed clearance after the start of treatment (indicating resistance).
Percentages of patients with P. falciparum parasitaemia on day 3 after treatment with an ACT (2006–2010)
A high percentage of hospital-acquired infections are caused by highly resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci.
Staphylococcus aureus (hospital isolates): percentage of methicillin-resistant strains, 2007, Latin America and the Caribbean
Resistance is an emerging concern for treatment of HIV infection, following the rapid expansion in access to antiretroviral medicines in recent years; national surveys are underway to detect and monitor resistance.
Ciprofloxacin is the only antibiotic currently recommended by WHO for the management of bloody diarrhoea due to Shigella organisms, now that widespread resistance has developed to other previously effective antibiotics. But rapidly increasing prevalence of resistance to ciprofloxacin is reducing the options for safe and efficacious treatment of shigellosis, particularly for children. New antibiotics suitable for oral use are badly needed.
AMR has become a serious problem for treatment of gonorrhoea (caused by Neisseria gonorrhoeae), involving even "last-line" oral cephalosporins, and is increasing in prevalence worldwide. Untreatable gonococcal infections would result in increased rates of illness and death, thus reversing the gains made in the control of this sexually transmitted infection.
New resistance mechanisms, such as the beta-lactamase NDM-1, have emerged among several gram-negative bacilli. This can render powerful antibiotics, which are often the last defence against multi-resistant strains of bacteria, ineffective.

What drives antimicrobial resistance?

Inappropriate and irrational use of medicines provides favourable conditions for resistant microorganisms to emerge and spread. For example, when patients do not take the full course of a prescribed antimicrobial or when poor quality antimicrobials are used, resistant microorganisms can emerge and spread.
Underlying factors that drive AMR include:
  • inadequate national commitment to a comprehensive and coordinated response, ill-defined accountability and insufficient engagement of communities;
  • weak or absent surveillance and monitoring systems;
  • inadequate systems to ensure quality and uninterrupted supply of medicines
  • inappropriate and irrational use of medicines, including in animal husbandry:
  • poor infection prevention and control practices;
  • depleted arsenals of diagnostics, medicines and vaccines as well as insufficient research and development on new products.

Combat drug resistance: no action today, no cure tomorrow

The emergence of AMR is a complex problem driven by many interconnected factors; single, isolated interventions have little impact. A global and national multi-sectoral response is urgently needed to combat the growing threat of AMR.

WHO's response

WHO is engaged in guiding the response to AMR through:
  • policy guidance, support for surveillance, technical assistance, knowledge generation and partnerships, including through disease prevention and control programmes;
  • essential medicines quality, supply and rational use;
  • infection prevention and control;
  • patient safety;
  • laboratory quality assurance.
WHO has selected combating antimicrobial resistance as the theme for World Health Day 2011. On this day, WHO issues an international call for concerted action to halt the spread of antimicrobial resistance and recommends a six-point policy package for governments.
WHO calls on all key stakeholders, including policy-makers and planners, the public and patients, practitioners and prescribers, pharmacists and dispensers, and the pharmaceutical industry, to act and take responsibility for combating antimicrobial resistance.

Utah Curriculum for Nursing Assistant Training

Utah Curriculum for Nursing Assistant Training
Corresponding pages from
Hartman’s Nursing
Assistant Care: The Basics, 3rd Edition
Hartman Publishing, Inc. (formerly
The Nursing
Assistant's Handbook
1. Explain the purpose of health care organizations such
as long-term care, home health agency and acute care
Ch 1, pp 1-3
2. Identify members of the health care team in terms of
their roles and responsibilities
Ch 1, pp 5-7
3. List the basic responsibilities of the health care
Ch 1, pp 3-4, 8-17
4. Identify professional requirements related to
certification/registration requirements
Ch 10, pp 231-232
5. Identify scope of practice Ch 1, pp 7-8
6. Identify beginning procedure actions Ch 6, pp 117-118
1. Describe verbal, non-verbal and body language as
forms of communication
Ch 2, pp 20-29
2. Identify the senses used when observing Ch 2, p 22
3. Discuss how and when to report observations Ch 2, pp 20-21; we have observing and reporting
lists throughout the textbook. In Chapter 4, our
anatomy & physiology and common diseases
chapter, these lists exist for every body system,
beginning on page 74.
4. Identify the importance of documentation Ch 1, pp 17-18; Ch 2, pp 20-21
- Explain the relationship between microorganisms and
Ch 2, pp 43-44
- List how microorganisms are spread Ch 2, pp 43-44
- Explain the body's defenses against infection Ch 2, pp 43-44
- Explain Standard(Universal) Precautions Ch 2, pp 43-53
- Recognize sterile and unsterile supplies Ch 2, p 50
- Explain the principles of disinfection Ch 2, pp 50-52
- Explain personal and environmental hygiene Ch 2, pp 43-53
- Explain OSHA Ch 2, p 33
- Identify four safety measures that should be used for
patient care
Ch 2, pp 29-34
- List five fire prevention rules health care assistants
should follow
Ch 2, pp 33-35
- Identify potential hazards that may occur in any setting
and the role of the Health Care Assistant in correcting
the potential hazards
Ch 2, pp 29-34
- Describe the step-by-step procedure a health care
assistant should follow if a fire occurs
Ch 2, pp 33-35
- Describe symptoms of a foreign body airway
Ch 2, pp 36-37
- Differentiate between life threatening and non-life
threatening emergencies
Ch 2, pp 35-43
- List basic physical needs Ch 4, pp 73-103
- List basic emotional needs Ch 3, pp 56-65
- Identify behavior that results when basic needs are not
Ch 2, pp 25-29; Ch 3, pp 66-67; Ch 5, pp 111-114
- Recognize age appropriate physical and behavioral
changes in regards to the patient's sexuality
Ch 3, p 57
- Explain the role of a health care assistant in regard to a
patient's sexuality
Ch 3, p 57
- Recognize, understand and respect a pateint's need for
spirituality in whatever form it may be expressed
Ch 3, pp 59-60
- Explain the role of the health care assistant in helping
to meet the patient's basic needs
Ch 3, pp 56-61
- Describe principles of body mechanics Ch 2, pp 30-31
- Describe how to protect oneself from injury before and
during moving a patient
Ch 2, pp 30-31; Ch 6, pp 147-158
- Describe the principles of positioning Ch 6, pp 147-158
- Explain the importance of preventing the complications
of immobility
Ch 3, p 61; Ch 6, pp 118-121; Ch 9, p 215
- Describe the patient's need for rest and sleep Ch 7, pp 191-195
- Explain how a Health Care Assistant can help a patient
meet their activity needs
Ch 3, p 61; Ch 9, p 215
- Describe how a Health Care Assistant can assist a
patient experiencing pain
Ch 7, pp 175-177
- Explain how a Health Care Assistant can make a
patient's environment comfortable and safe
Ch 7, pp 190-191
- Explain how a Health Care Assistant can maintain a
clean environment
Ch 2, pp 50-51; Ch 7, pp 190-191
- Explain proper positioning/answering of call lights and
alternative monitoring devices
Ch 7, p 190; Included as a step in every
- Describe general furniture/equipment and its proper
Ch 2, pp 50-51; Ch 7, pp 190-191
- Explain the general guidelines to remember in making
a bed
Ch 7, pp 192-195
- List factors which can affect vital signs Ch 7, pp 164-179
- State normal ranges for vital signs Ch 7, pp 164-179
- Describe when vital signs should be measured Ch 7, pp 164-179
- Explain the importance of cleanliness and skin care Ch 6, pp 118-121
- Describe the general rules related to bathing patients
and the observations to make
Ch 6, pp 121-130
- Identify the safety precautions for patients taking tub
baths or showers
Ch 6. pp 128-130
- Identify the purposes of perineal care Ch 6, pp 124-125
- Explain the importance of oral hygiene and list the
observations to report
Ch 6, pp 138-143
- Identify the purposes of a back massage Ch 6, pp 125-126
- Explain the importance of hair care and shaving Ch 6, pp 126-128, 133-135
- Explain the importance of nail and foot care Ch 6, pp 130-132
- Explain basic anatomy and physiology of digestive
Ch 4, pp 91-94
- Identify common disorders of digestive system Ch 4, pp 91-94
- Define a well balanced diet Ch 8, pp 197-200
- Name the four food groups in the food pyramid and
list foods included in each group
Ch 8, pp 197-200
- Describe principles of safe food storage Not Included
- Describe common therapeutic diets and the purpose of
Ch 8, pp 201-203
- Describe preventative measures for aspiration Ch 8, pp 211-212
- Identify basic structures and functions of the urinary
Ch 4, pp 89-91
- Define terminology related to elimination Ch 6, pp 143-147; Ch 9, pp 225-226
- Demonstrate ability to perform skills outlined Ch 6, pp 143-147; Ch 9, pp 225-226
- Describe the structure and function of cells, tissues,
organs, and systems
Ch 4, pp 73-103
- Explain how body systems work together Ch 4, pp 73-103
- Know which changes in appearance or body function
should be reported to the nurse/supervisor
Ch 2, pp 20-21; we have observing and reporting
lists throughout the textbook. In Chapter 4, our
anatomy & physiology and common diseases
chapter, these lists exist for every body system,
beginning on page 74.
- Describe what cancer is Ch 4, pp 101-103
- Discuss how to care for patients who are experiencing
side effects of cancer and its treatments
Ch 4, pp 101-103
- Identify needs of the dying patient Ch 3, pp 67-71
- List and define the 5 stages of Kubler-Ross's grieving
Ch 3, pp 67-68
- Describe death with dignity Ch 3, pp 69-70
- Identify physical care of the dying patient Ch 3, pp 67-71
- Perform post mortem care Ch 3, p 71
- Describe the process for certification as a CNA Ch 10, pp 231-232
- Explain the difference between certification and
1. Application of Restraints
Procedure for application of restraint not
included; restraint alternatives discussed in
Ch 7, pp 179-182
2. Communication Skill
Reporting Ch 2, pp 20-21; we have observing and reporting
lists throughout the textbook. In Chapter 4, our
anatomy & physiology and common diseases
chapter, these lists exist for every body system,
beginning on page 74.
Verbal Ch 2, pp 20-21
Written /Charting Ch 1, pp 17-18
Admission of Patient Ch 7, pp 160-162
Discharge of Patient Ch 7, pp 163-164
Transfer of Patient(I.e. another room, another facilty) Ch 7, pp 162-163
3. Infection Control
Hand Washing Ch 2, pp 45-47
Gloving - Putting On/Removing PPE(Gown, Mask,
Ch 2, pp 47-50
Standard Universal Precautions Ch 2, pp 44-55
Isolation Ch 2, pp 51-53
Safe Handling of Waste & Linens Ch 2, pp 50-51
Maintain Sterile Field Ch 2, pp 43-53
4. Safety
Proper Body Mechanics Ch 2, pp 30-31
Care of Patient After Falls Ch 2, pp 31-32
Care of Choking Patient Ch 2, pp 36-37
Controlling Bleeding Ch 2, p 39
First Aid - (Fainting, Seizures, Shock) Ch 2, pp 29-34
CPR Handout in instructor's guide
5. Body Mechanics
Assist Patient Into/Out of Bed Ch 6, pp 154-159
Assist Patient Onto/Off of the Toilet Ch 6, pp 146-147
One Person Assist/Pivot Transfer Ch 6, pp 154-159
Two Person Assist Not Included
Total Body Lift Not Included
Use of a Transfer/Safety/Gait Belt Ch 9, pp 215-218
Use of a Mechanical Lift Ch 6, pp 157-159
Assisting to Transfer a Hemiplegic Patient Ch 4, p 80
Assisting to Transfer a Total Hip Patient Ch 4, p 77
Lifting with use of a Lift Sheet Ch 6, pp 120-121
Log Rolling Ch 6, pp 152-153
A. Positioning
Prone Ch 6, p 148
Semi-Prone/Sims Ch 6, p 148
Supine Ch 6, pp 147-148
Lateral Ch 6, p 148
Semi-Fowler's Not Included
High-Fowler's Ch 6, p 148
In a Wheel Chair Ch 6, pp 154-157
In a Geri-Chair(if permitted by facility) Ch 6, p 155
With Foot Board and/or Bed Cradle Ch 6, pp 120-121
Trendelenberg Not Included
Reverse Trendelenberg Not Included
Ambulating Ch 9, pp 215-218
Ambulating a Blind Patient Ch 9, p 216
B. Assisting the Patient in the Use of:
Cane Ch 9, pp 215-218
Crutches Ch 9, pp 215-218
Walker Ch 9, pp 215-218
C. Range of Motion
Active Ch 9, pp 221-225
Passive Ch 9, pp 221-225
Pressure Sore Prevention Ch 6, pp 118-121
D. Use of: Prosthetic Devices
Braces Ch 9, pp 220-221
Orthotics Ch 9, pp 220-221; Ch 2, p 25; Ch 6, pp 121, 142-
6. Environment
Bed Making Ch 7, pp 192-195
Occupied: Complete/Foundation Change/Surgical Ch 7, pp 192-194
Linen Handling Ch 2, pp 50-51
Call Light Position Ch 7, p 190; Included as a step in every
7. Vital Signs/ Height & Weight
Oral Temperature Ch 7, pp 166-168
Rectal Temperature Ch 7, pp 168-169
Tympanic Temperature Ch 7, p 169
Axillary Temperature Ch 7, pp 170-171
Radial Pulse Ch 7, p 171
Apical Pulse Not Included
Carotid Pulse Not Included
Respiration Ch 7, pp 171-172
Blood Pressure By Pulse Obliteration Ch 7, pp 173-175
Weight Ch 7, pp 177-178
Height Ch 7, pp 177-179
8. Hygiene/Grooming
Completed Bed Bath Ch 6, pp 122-125
Partial Bed Bath Ch 6, p 122
Shower Chair/Cart Ch 6. pp 128-130
Tub Ch 6, pp 121-130
Skin Care Ch 6, pp 118-121
Back Rub/Massage Ch 6, pp 125-126
Peri-Care Ch 6, pp 124-125
Toileting Ch 6, pp 143-147
Hair Care/Shampoo Ch 6, pp 126-128, 133
Mouth Care Ch 6, pp 138-143
Dentures Ch 6, pp 142-143
Natural Teeth Ch 6, pp 138-142
Unconscious Patient Ch 6, pp 140-141
Shave - Electric Ch 6, pp 134-135
AM Care Ch 6, p 117
HS Care Ch 6, p 117
Nail Care/Foot Care Ch 6, pp 130-132
Dressing/Undressing Patient Ch 6, pp 135-138
9. Nutrition
Demonstrate the Abdominal Thrust Ch 2, pp 36-37
Assist Patient with Meals Ch 8, pp 207-210
Measure and Record Food and Fluid Intake Ch 7, pp 182-183
Feed the Patient Ch 8, pp 207-210
10. Elimination
Bathroom Privileges with Assist Ch 6, pp 143-147
A. Catheter Care
Ch 7, pp 186-188
Positioning Bag and Tubing Ch 7, pp 186-188
Peri-Care Ch 6, pp 124-125
Emptying Bag Handout in instructor's guide
Replacing External Male Catheter Ch 7, pp 186-188
Change Bag to Leg Bag or Other Drainage Bag Not Included
Documentation of Output Ch 7, pp 182-183
Decontamination Procedure Ch 6, pp 124-125
Bedpan/Urinal Ch 6, pp 143-145
Bedside Commode Ch 6, pp 146-147
Incontinent Care Ch 6, pp 124-125, 143-147
B. Specimen Collection
Simple Urinalysis Ch 7, pp 184-185
Simple Stool Ch 7, pp 185-186
Clean Catch/Mid Stream Ch 7, pp 184-185
Sterile Specimen Ch 2, p 53
C. Enemas
Preparation For Positioning Handout in instructor's guide
Post Enema Care Handout in instructor's guide
Recording of Results Handout in instructor's guide
Enema Administration(if permitted by facility)
Handout in instructor's guide
D. Ostomy Care
Colostomy Ch 4, p 93
Ileostomy Ch 4, p 93
Emptying Ch 4, pp 93-94
Observation and Reporting Ch 4, pp 93-94
Appliance Application(if permitted by facility) Not Included
11. Body Systems
Observe For Changes and/or
Breakdown/Integumentary System
Ch 4, pp 73-74; Ch 6, pp 118-121
A. Musculoskeletal
Warm Compresses Handout in instructor's guide
Warm Soak Handout in instructor's guide
K-Pad Handout in instructor's guide
Ice Bag/Commercial Cold Pack Handout in instructor's guide
Casts/Dressings/Elastic Bandages Ch 7, pp 195-196
Observation and Reporting Ch 4, pp 75-78
B. Neurological System/Mental Illness
Observe For Changes Ch 5, pp 104-116
C. Endocrine System
Urine Testing Ch 7, pp 184-185
Finger Stick Blood Glucose Test Ch 4, p 97
Diabetic Skin Care Ch 4, p 97
Observe for Changes Ch 4, pp 94-97
D. Sensory System
Care of Glasses/Contacts Ch 2, p 26
Care of Hearing Aids Ch 2, pp 25-26
Observe for Changes Ch 4, pp 83-84
E. Cardiovascular System
Application of Antiembolism Stockings Ch 6, pp 137-138
F. Respiratory System
Oxygen Monitoring Ch 7, pp 188-190
Applies Nasal Cannula Not Included
Applies Oxygen Mask Not Included
Maintains Humidifier Bottle Not Included
Able to Check Oxygen Flow Rate Not Included
Skin Care Ch 7, pp 188-190
Observation for Changes Ch 7, pp 188-190
G. Digestive System
Feeding Patient with Swallowing Difficulties Ch 8, pp 210-212
Bowel Care Ch 4, pp 91-94
Observe for Changes Ch 4, pp 91-94
H. Urinary System
Care of Foley Catheter Ch 7, pp 186-188
Observe for Changes Ch 4, pp 89-91
I. Reproductive System
Observe for Changes Ch 4, pp 97-99
12. Death and Dying
Post Mortem Care Ch 3, p 71

Sunday, May 26, 2013

BRCA Choices Not Affordable for Many US Women

BRCA Choices Not Affordable for Many US Women

Roxanne Nelson
May 23, 2013 Angelina Jolie's public announcement of her decision to undergo a double prophylactic mastectomy after learning she was positive for a mutation in the BRCA1 gene has certainly put genetic testing squarely into the limelight.
However, her story has also caused a ripple of backlash across the Internet, exposing the realities of many US women who have little choice on the issue, especially if they do not have the health insurance, the money, or the means to undertake a series of extended medical procedures.
Several posts have expressed sadness, anger, and resentment over the media storm surrounding Jolie. Although people appreciate the difficulty of making such a decision and the courage of going so public with it, they also bring attention to the other side of the story.
"The bigger issue is that many women in America simply cannot afford to be sick," says one blogger, writing in "The issue of affordability has been swept under the carpet. The media has instantly polarized the debate in terms of women who may or may not entreat medical intervention. "
In a commentary published in the LA Times, writer Robin Abcarian notes, "Unlike Jolie, most people do not live in a world where cost, even to save one's life, is no object." She commends Jolie for sharing her story, adding, "It would be a lovely thing if everyone had access to the high level of care she has received."
Some of the articles took a stronger and more acrid tone. A teacher in New Jersey, also with a strong family history of cancer, reported that Jolie's account "upset me."
"That's good for her; she's got the best health care and she's got money. She doesn't have to worry about taking off of work. She doesn't have to worry about taking care of her family, cooking or cleaning — the things that the normal woman would have to do," she wrote.

Disparities and Dangers

Disparities in access to healthcare is not a new revelation — it is an issue that has been at the political forefront in the United States — and with no real solutions at hand, Jolie's story has served to amplify that rift.
There are an estimated 940,000 BRCA mutation–carriers living in the United States, but only about 10% are aware of their status, commented Lisa Schlager, vice president, Community Affairs and Public Policy at FORCE, a national nonprofit organization focused on hereditary breast and ovarian cancer. "While there are multiple factors involved, many of the women simply can't afford to find out," she told Medscape Medical News.
"That is unfortunate, as this is the direction where medicine is going," she commented in an interview. "We have the ability to use this information to customize and personalize care, and we are hindering this progress."
We have the ability to use this information to customize and personalize care, and we are hindering this progress.
Schlager believes that the huge publicity surrounding Jolie's story has helped bring genetic testing to the forefront, along with all of the gaps and inconsistencies. But there is also the danger that Jolie's story might tend to simplify how extensive the entire process of undergoing a prophylactic mastectomy actually is.
"We need to explain that this is not an easy surgery," she said. "This is not the same as getting a breast enhancement. Things can go wrong, there can be significant complications, and recovery can take a while."
It is also not a 1-step deal to remove and reconstruct the breast, and in fact, multiple surgeries may be needed during reconstruction, to reach the desired effect. "We don't want to scare women away, we just want them to go into it with their eyes open," she said.
Jolie is not the first celebrity who has spoken openly about opting for double mastectomies. Actress Christina Applegate was diagnosed with breast cancer at age 36, and after finding out that she was positive for the BRCA gene mutation, opted for a bilateral mastectomy. But she already had a cancer diagnosis, whereas Jolie's surgery was prophylactic.
The dilemma of whether or not to undergo the procedure is illustrated by a story from the United Kingdom in which a popular television presenter, Kristie Allstrop, has talked about her family history of breast cancer and her decision to opt for monitoring (for now), whereas her sister Fiona decided to undergo a double prophylactic mastectomy. Although Fiona had tested negative for the BRCA1 and BRCA2 genes, medical experts believed that, given the family's medical history, she probably carried a yet unidentified mutant gene, according to press reports.

Expensive Process

The whole process of counseling, genetic testing, and any preventive actions taken as a result of testing is expensive.
For a start, the cost of the BRCA test alone is about $4000. Preventive surgery and more frequent screenings can be prohibitively expensive, even if a woman does have insurance. Especially with surgery, indirect costs, such as those associated with taking time off from work and childcare, also need to be figured into the equation.
But there is an upside to the story. Although genetic counseling, testing, and preventive options will continue to remain out of reach for many women in the foreseeable future, there are options, and the tide may slowly be shifting.
Many insurers will cover the cost of prophylactic mastectomies, according to Jen Flory, JD, "although it often takes filing both an internal and external appeal to get it."
"The BRCA testing itself should be covered by any plan started after March 23, 2010, as Health and Human Services has found this to be one of the mandatory free preventative care measures covered under the Affordable Care Act [ACA]," said Flory, who is director of the Cancer Legal Resource Center, Los Angeles, California. "Older insurance companies generally charge a co-pay or coinsurance for the test."
Schlager noted that in her experience, most major insurers will cover genetic counseling and testing, provided that the patient meets the guidelines set by the National Comprehensive Cancer Network (NCCN). "The guidelines are very far as personal history or family history. So if you don't meet them, you probably won't be covered," she added.
When it goes into full effect, the ACA will at minimum provide genetic counseling to certain persons and their families, she added, although there are some caveats. "Men do not qualify for BRCA testing under the ACA," Schlager said. "And Medicare will only cover it if you already have cancer."
The rationale for that, believes Schlager, is that genetic cancers tend to strike at a younger age, and Medicare is dealing with an older population. "But still, it would be good to be identified as a carrier, as that would be important information for the family," she said.
Medicaid coverage is also restrictive, and coverage of the test varies state by state, according to Flory. "Those that cover it generally have stringent risk factors and cover it on a once-in-a-lifetime basis."
Myriad Genetics, currently the only company offering testing for the BRCA gene, also offers free testing for low-income women and those without any insurance. They have very stringent eligibility criteria, Schlager pointed out, but it still is an option, and many women can get tested that way. As previously reported by Medscape Medical News, Myriad has been enmeshed for several years in a legal battle over its patent rights to the BRCA genes, and the case is currently being deliberated by the US Supreme Court. Oral arguments were heard on April 15, and a decision is expected this summer.

Prohibitive Costs

But once a woman has received genetic counseling and opted for testing — then what?
Information is a scary thing if you can't do anything with it," said Schlager. And for some women, that is where they will reach an impasse.
Information is a scary thing if you can't do anything with it.
Many insurance companies will pay for preventive services, provided they meet certain criteria, such as those outlined by the NCCN. If an insurance company covers a mastectomy, whether prophylactic or for cancer treatment, it is obligated to cover the costs of the reconstructive surgery, owing to regulations in the Women's Health and Cancer Rights Act (WHCRA), which was signed into law in 1998.
But unlike Jolie, women may be limited in their choice of plastic surgeons, depending on their insurance coverage. They may only be able to use surgeons within their insurer's network, for example, and some plastic surgeons do not take insurance at all. It can also be difficult to find a surgeon willing to take Medicaid, owing to the very low reimbursement.
In addition, health insurance will generally not cover everything. There could be co-payments and incidentals that can bring out-of-pocket expenses into the 5-figure realm. Schlager, who underwent prophylactic mastectomy herself in the late 1990s, notes that even though she was covered under a good insurance policy, over the years she has incurred about $20,000 in out-of-pocket expenses.
The cost of a prophylactic mastectomy, with reconstruction, can run upwards of $100,000 when the fees from the hospital, anesthesia, surgeons, medications, and incidentals are factored in. Add in possible complications, such as an infection, and the cost can easily double. On, where women in the forum have compared notes, they report having to pay between $10,000 and $25,000 in co-payments or fees that their insurance company will not pick up. One noted that her insurer only paid $6,500 of the $28,000 it cost for reconstruction, while another reported $40,000 in out-of-pocket costs because of her 20% co-pay.
Even surveillance can be costly. Mammograms are usually covered, and there are often low-cost options for those, commented Heather MacDonald, MD, assistant professor of clinical obstetrics and gynecology and breast surgery at the University of Southern California (USC), in Los Angeles. "But MRIs [magnetic resonance images], which are also recommended, are very expensive, and it can be difficult getting insurers to pay for them."
For women without insurance, options become even slimmer, and most would be unable to afford surgery. Although not the only option, even surveillance and chemoprevention can be beyond the means of many.

Perseverance and Ingenuity

Dr. MacDonald, however, is optimistic that with perseverance and ingenuity, many more people can have access to healthcare. With her colleagues, she runs a high-risk clinic at USC, where they offer a wide range of preventive options, including mammograms, MRIs, pelvic ultrasounds, medications, and surgical prophylaxis "if that's what patients choose."
"There is a hodgepodge of programs that we can get patients enrolled in," Dr. MacDonald said in an interview. "We get creative, and it is rare that we don't have something that we can offer high-risk women."
She explained that they have a 3-year grant from the Avon Foundation and that the Medicaid program in California (known as MediCal) will pay for BRCA testing for eligible patients. "So as the Affordable Care Act expands MediCal, we will be able to get more patients covered."
"So this is very much going to be a state-by-state issue as to how patients are covered under the Affordable Care Act," she added. "We are lucky in California that MediCal will cover BRCA testing for patients who really need it."
The MediCal model is set up so that women see a genetic counselor, but many patients cannot afford or lack access to one. In such cases, there are guidelines that are published by the American Congress of Obstetricians and Gynecologists (ACOG) and the NCCN that give very clear criteria as to who may benefit from testing, Dr. MacDonald explained. "If those patients have a primary care doctor and fall within the guidelines for testing, then their primary care doctor can order the test for them."
Dr. MacDonald emphasized that it is far better to involve a genetic counselor because it is a complicated process, but if that option is not available, then a physician can coordinate it. "MedicCal will cover, based on the NCCN guidelines," she noted.
She is optimistic that women in other parts of the country can also receive assistance. "It can be done," she said. "It required dedicated personal and outside money, and Avon was the fifth organization that we submitted our proposal to before someone gave us a chance. Anyone in LA County is eligible to join our program."
Dr. MacDonald points out that the women who are most likely to struggle are those in small rural areas, where access to care may already be problematic. It may be harder to find a physician who accepts Medicaid, because providers in these areas can be few and far between. It is also more difficult to access large academic medical centers, which often provide services at low cost or free of charge.
"Finding providers to take Medicaid is a problem and will continue to be, but it will hopefully get better," she noted, adding that under the ACA, more women may be able to obtain health insurance, which will open the door to more options.

Angelina Jolie's Mastectomy: BRCA Testing in the Spotlight

Angelina Jolie's Mastectomy: BRCA Testing in the Spotlight

Kate Johnson
May 16, 2013 Superstar Angelina Jolie's headline revelation this week about her positive genetic test for the BRCA1 mutation and subsequent double prophylactic mastectomy has stunned the world and put the entire field of breast cancer medicine on high alert.
Her story is "the epitome" of individualized medicine, said Eric Topol, MD, editor-in-chief of Medscape.
"She took charge by getting the test done, getting the critical information about whether she would be at risk for breast cancer and how high that risk would be, and then making a key decision of preventive surgery," said Dr. Topol, who is director, Scripps Translational Science Institute Chief Academic Officer, Scripps Health Professor of Genomics, the Scripps Research Institute.
With more than 1600 comments registered for Jolie's New York Times op-ed piece, there is little doubt about the intense public interest, which is already having a ripple effect in cancer clinics across the United States.
"With this publicity and her speaking out, I have a feeling there will be increased requests [for BRCA testing]," Sandra M. Swain, MD, president of the American Society of Clinical Oncology, told Medscape Medical News.
Angelina Jolie (REUTERS/Toby Melville)
"We already know from studies that women think they are at a higher risk of breast cancer than they actually are," said Dr. Swain, a breast cancer specialist and medical director of the Washington Cancer Institute at MedStar Washington Hospital Center.
"Hearing this, people may think, 'Oh, she's 37, maybe I also have that risk.' "
Indeed, there has already been an uptick in patient calls and emails at Moores Cancer Center at the University of California, San Diego. "People are just wondering about how to go about getting the test or more information," said Lisa Madlensky, PhD, CGC, a cancer geneticist and director of the center's Family Cancer Genetics Program, in an interview.
"I expect a lot of women are asking themselves if they should get tested or not because of a family history," said Jennifer Litton, MD, from the Department of Breast Medical Oncology, Division of Cancer Medicine, the University of Texas MD Anderson Cancer Center, in Houston.
"Overall, I think healthcare providers may expect increased questions about this testing," she told Medscape Medical News.

Assessing Risk

Unlike the average woman, who faces a breast cancer risk of about 12%, Jolie's risk before surgery was roughly 7-fold higher.
"My doctors estimated that I had an 87 percent risk of breast cancer and a 50 percent risk of ovarian cancer," wrote Jolie, whose mother was diagnosed with ovarian cancer at 46 years of age and died a decade later.
But physicians fielding questions and requests for BRCA testing from patients on the basis of a worrying family history "really need to be armed with information," said Dr. Swain.
"Primary care is going to be responsible for a lot of this, and so they're the ones who really need to be educated about what to do and not just be ordering this test on everybody. It's an expensive test, there are a lot of implications. I personally don't order the test — and I know a lot about it — so a primary care physician who really has no education in it should really not be ordering this test. I have a genetic counselor who does a full pedigree to see if they're at increased risk and need to be tested for a BRCA mutation".
"It's not something you want to automatically order," agreed Dr. Madlensky, who says that ideally, patients should be screened in primary care for red flags that might suggest the need for referral to genetic counseling — even before a test is considered.
"There are different types of BRCA testing, and knowing which one to order is a bit complicated, depending on ancestry, cancer diagnosis or not, known BRCA mutation in family or not," she said, adding that a patient's family history should not be taken at face value.
"A lot of times, the story that is in the family is not accurate. Breast cancer reporting is pretty good, but when people report they had a relative with ovarian cancer, often when we try to get those records, we find it was not ovarian but cervical or uterine or something not related to the BRCA genes."
Although there are no standardized criteria for selecting candidates for BRCA counseling, the National Cancer Institute, the National Comprehensive Cancer Network, and the US Preventive Services Task Force outline family history red flags, which generally point to first- and second-degree relatives with breast and/or ovarian cancers, especially at young ages:
  • 2 first-degree relatives (mother, daughter, or sister) diagnosed with breast cancer, one of whom was younger than 50 years
  • 3 or more first- or second-degree relatives (aunt or grandmother) diagnosed regardless of age
  • combination of first- and second-degree relatives diagnosed with breast and ovarian cancer regardless of age
  • first-degree relative with bilateral breast cancer
  • breast cancer in a male relative
  • combination of 2 or more first- or second-degree relatives with ovarian cancer
  • For women of Ashkenazi Jewish descent: any first-degree or 2 second-degree relatives on same side of family diagnosed with breast or ovarian cancer
Although Jolie has not publicly discussed the full extent of her family history beyond her mother, sources suggest that other relatives have likely been either diagnosed with similar cancers or have tested positive for the BRCA mutation.
We really ideally want the first test in the family to be on someone who's had a cancer diagnosis. Dr. Lisa Madlensky
But even if a person's history involves only 1 first-degree relative, BRCA testing "could be" appropriate in some cases, especially if that relative can no longer be tested herself, said Dr. Madlensky. BRCA testing should be viewed as a family undertaking, preferably with the cancer patient central, she added.
"We really ideally want the first test in the family to be on someone who's had a cancer diagnosis. That way, we can figure out whether cancer was result of a BRCA mutation or not. If that test is negative, then there's no need to go and test any of the other family members," she explained. "That's something most people — including physicians — are not aware of," she added.
Sometimes, discussing why a patient should not pursue testing can also be very helpful, commented Jennifer Litton, MD, assistant professor of breast medical oncology, the University of Texas MD Anderson Cancer Center.
The BRCA gene only accounts for 5% to 10% of breast cancer... Dr. Jennifer Litton
"It is important for everyone to realize and to communicate when discussing with patients that a mutation in the BRCA gene only accounts for 5% to 10% of breast cancer, and so for the vast majority of women who get breast cancer, it is not due to a mutation in this gene," she said.

Jolie's Decision

Prophylactic double mastectomy is a choice that often sparks debate, sometimes shock and disbelief, and always emotion.
"Once I knew that this was my reality, I decided to be proactive and to minimize the risk as much I could," wrote Jolie. "I started with the breasts, as my risk of breast cancer is higher than my risk of ovarian cancer."
Speaking to the New York Times, breast surgeon Susan Love, MD, said, "When you have to cut off normal body parts to prevent a disease, that's really pretty barbaric when you think about it."
But Jolie's decision was "a very, very solid choice, a reasonable choice, especially in the face of such alarming high risk of breast cancer and ovarian cancer," said Dr. Swain.
Dr. Madlensky agreed. "For someone who tests positive for BRCA mutation, its actually not radical at all. Its one of the options that is medically appropriate."
Other options for women with this mutation are medication (tamoxifen or raloxifene) or screening, "but we know screening is not preventative. It only hopes to find a cancer as early as possible," said Dr. Litton.

Eliminating Fear

For Jolie, the surgery eliminated fear. "My chances of developing breast cancer have dropped from 87 percent to under 5 percent. I can tell my children that they don't need to fear they will lose me to breast cancer," she wrote. "The decision to have a mastectomy was not easy. But it is one I am very happy that I made.... I do not feel any less of a woman. I feel empowered that I made a strong choice that in no way diminishes my femininity."
Much of the work physicians may face in light of Jolie's story will involve providing information and alleviating the kind of anxiety Jolie described — time-consuming tasks, especially because many women tend to overestimate their risk, said Mary Jane Esplen, RN, PhD, head, Program of Psychosocial and Psychotherapy Research in Cancer Genetics at Toronto General Research Institute, in Canada.
Dr. Esplen has found psychosocial oncology counseling helpful for women who cannot always accept the facts when they are told that their risk is low.
"Risk perceptions are not always based on what we might refer to as rational knowledge," she said. "We saw that just giving information alone wasn't modifying their own internal sense of risk. It had to do with family history, sometimes there were losses in families and it had to do with grief, and it had to do with this imprint that's left with a family history and the experiences associated with that."
Referring patients to genetic counseling can also be effective in diffusing anxiety, said Dr. Madlensky, debunking the notion that such counselors are hard to find.
"One of the biggest myths is that its hard to get access to a cancer genetic specialist," she said, but that is not the case. The National Society of Genetic Counselors 2012 professional status survey found that wait times for the vast majority of its members were within a 2-week period, she noted.


What Is a Pacemaker?

A pacemaker is a small device that's placed in the chest or abdomen to help control abnormal heart rhythms. This device uses electrical pulses to prompt the heart to beat at a normal rate.
Pacemakers are used to treat arrhythmias (ah-RITH-me-ahs). Arrhythmias are problems with the rate or rhythm of the heartbeat. During an arrhythmia, the heart can beat too fast, too slow, or with an irregular rhythm.
A heartbeat that's too fast is called tachycardia (TAK-ih-KAR-de-ah). A heartbeat that's too slow is called bradycardia (bray-de-KAR-de-ah).
During an arrhythmia, the heart may not be able to pump enough blood to the body. This can cause symptoms such as fatigue (tiredness), shortness of breath, or fainting. Severe arrhythmias can damage the body's vital organs and may even cause loss of consciousness or death.
A pacemaker can relieve some arrhythmia symptoms, such as fatigue and fainting. A pacemaker also can help a person who has abnormal heart rhythms resume a more active lifestyle.

Understanding the Heart's Electrical System

Your heart has its own internal electrical system that controls the rate and rhythm of your heartbeat. With each heartbeat, an electrical signal spreads from the top of your heart to the bottom. As the signal travels, it causes the heart to contract and pump blood.
Each electrical signal normally begins in a group of cells called the sinus node or sinoatrial (SA) node. As the signal spreads from the top of the heart to the bottom, it coordinates the timing of heart cell activity.
First, the heart's two upper chambers, the atria (AY-tree-uh), contract. This contraction pumps blood into the heart's two lower chambers, the ventricles (VEN-trih-kuls). The ventricles then contract and pump blood to the rest of the body. The combined contraction of the atria and ventricles is a heartbeat.
For more information about the heart's electrical system and detailed animations, go to the Health Topics How the Heart Works article.


Faulty electrical signaling in the heart causes arrhythmias. Pacemakers use low-energy electrical pulses to overcome this faulty electrical signaling. Pacemakers can:
  • Speed up a slow heart rhythm.
  • Help control an abnormal or fast heart rhythm.
  • Make sure the ventricles contract normally if the atria are quivering instead of beating with a normal rhythm (a condition called atrial fibrillation).
  • Coordinate electrical signaling between the upper and lower chambers of the heart.
  • Coordinate electrical signaling between the ventricles. Pacemakers that do this are called cardiac resynchronization therapy (CRT) devices. CRT devices are used to treat heart failure.
  • Prevent dangerous arrhythmias caused by a disorder called long QT syndrome.
Pacemakers also can monitor and record your heart's electrical activity and heart rhythm. Newer pacemakers can monitor your blood temperature, breathing rate, and other factors. They also can adjust your heart rate to changes in your activity.
Pacemakers can be temporary or permanent. Temporary pacemakers are used to treat short-term heart problems, such as a slow heartbeat that's caused by aheart attackheart surgery, or an overdose of medicine.
Temporary pacemakers also are used during emergencies. They might be used until your doctor can implant a permanent pacemaker or until a temporary condition goes away. If you have a temporary pacemaker, you'll stay in a hospital as long as the device is in place.
Permanent pacemakers are used to control long-term heart rhythm problems. This article mainly discusses permanent pacemakers, unless stated otherwise.
Doctors also treat arrhythmias with another device called an implantable cardioverter defibrillator (ICD). An ICD is similar to a pacemaker. However, besides using low-energy electrical pulses, an ICD also can use high-energy pulses to treat life-threatening arrhythmias.



By Mayo Clinic staff
Bradycardia is a slower than normal heart rate. The heart usually beats between 60 and 100 times a minute in an adult at rest. If you have bradycardia (brad-e-KAHR-de-uh), your heart beats fewer than 60 times minute.
Bradycardia can be a serious problem if the heart doesn't pump enough oxygen-rich blood to the body. For some people, however, bradycardia doesn't cause symptoms or complications.
An implanted pacemaker and other treatments may correct bradycardia and help your heart maintain an appropriate rate.

Multiple Sclerosis

Multiple sclerosis

From Wikipedia, the free encyclopedia
Multiple sclerosis
Classification and external resources

Demyelination by MS. The CD68 colored tissue shows several macrophages in the area of the lesion. Original scale 1:100
eMedicineneuro/228 oph/179emerg/321 pmr/82radio/461
Multiple sclerosis (MS), also known as "disseminated sclerosis" or "encephalomyelitis disseminata", is an inflammatory disease in which the fattymyelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum ofsigns and symptoms.[1] Disease onset usually occurs in young adults, and it is more common in women.[1] It has a prevalence that ranges between 2 and 150 per 100,000.[2] MS was first described in 1868 by Jean-Martin Charcot.[3]
MS affects the ability of nerve cells in the brain and spinal cord to communicate with each other effectively. Nerve cells communicate by sending electrical signals called action potentials down long fibers called axons, which are contained within an insulating substance called myelin. In MS, the body's own immune system attacks and damages the myelin. When myelin is lost, the axons can no longer effectively conduct signals.[4] The namemultiple sclerosis refers to scars (sclerae-—better known as plaques or lesions) particularly in the white matter of the brain and spinal cord, which is mainly composed of myelin.[3] Although much is known about the mechanisms involved in the disease process, the cause remains unknown. Theories include genetics or infections. Different environmental risk factors have also been found.[4][5]
Almost any neurological symptom can appear with the disease, and the disease often progresses to physical and cognitive disability.[4] Psychiatric symptoms and difficult thinking may also occur.[6] MS takes several forms, with new symptoms occurring either in discrete attacks (relapsing forms) or accumulating over time (progressive forms).[7] Between attacks, symptoms may go away completely, but permanent neurological deficits often occur, especially as the disease advances.[7]
There is no known cure for multiple sclerosis. Treatments attempt to return function after an attack, prevent new attacks, and prevent disability.[4] MS medications can have adverse effects or be poorly tolerated, and many people pursue alternative treatments, despite the lack of supporting scientific study. The prognosis is difficult to predict; it depends on the subtype of the disease, the individual's disease characteristics, the initial symptoms and the degree of disability the person experiences as time advances.[8] Life expectancy of people with MS is 5 to 10 years lower than that of the unaffected population.[1]

Signs and symptoms

Main symptoms of multiple sclerosis
A person with MS can suffer almost any neurological symptom or sign, including changes in sensation such as loss of sensitivity or tingling, pricking or numbness (hypoesthesia and paresthesia), muscle weakness, clonusmuscle spasms, or difficulty in moving; difficulties with coordination and balance (ataxia); problems in speech (dysarthria) or swallowing (dysphagia), visual problems (nystagmusoptic neuritis including phosphenes,[9][10] or diplopia),fatigueacute or chronic pain, and bladder and bowel difficulties.[1] Cognitive impairment of varying degrees and emotional symptoms of depression orunstable mood are also common.[1] Uhthoff's phenomenon, an exacerbation of extant symptoms due to an exposure to higher than usual ambient temperatures, and Lhermitte's sign, an electrical sensation that runs down the back when bending the neck, are particularly characteristic of MS although not specific.[1] The main clinical measure of disability progression and symptom severity is the Expanded Disability Status Scale or EDSS.[11]
Symptoms of MS usually appear in episodic acute periods of worsening (called relapses, exacerbations, bouts, attacks, or "flare-ups"), in a gradually progressive deterioration of neurologic function, or in a combination of both.[7] Multiple sclerosis relapses are often unpredictable, occurring without warning and without obvious inciting factors with a rate rarely above one and a half per year.[1] Some attacks, however, are preceded by common triggers. Relapses occur more frequently during spring and summer.[12] Viral infections such as the common coldinfluenza, or gastroenteritis increase the risk of relapse.[1] Stress may also trigger an attack.[13] Pregnancy affects the susceptibility to relapse, with a lower relapse rate at each trimester of gestation. During the first few months after delivery, however, the risk of relapse is increased.[1] Overall, pregnancy does not seem to influence long-term disability. Many potential triggers have been examined and found not to influence MS relapse rates. There is no evidence that vaccination and breast feeding,[1] physical trauma,[14] or Uhthoff's phenomenon[12] are relapse triggers.


Most likely MS occurs as a result of some combination of genetic, environmental and infectious factors,[1] and possibly other factors like vascular problems.[15] Epidemiological studies of MS have provided hints on possible causes for the disease. Theories try to combine the known data into plausible explanations, but none has proved definitive.


HLA region of Chromosome 6. Changes in this area increase the probability of suffering MS.
MS is not considered a hereditary disease. However, a number of genetic variations have been shown to increase the risk of developing the disease.[16]
The risk of acquiring MS is higher in relatives of a person with the disease than in the general population, especially in the case of siblings, parents, and children.[4] The disease has an overall familial recurrence rate of 20%.[1] In the case of monozygotic twins, concordance occurs only in about 35% of cases, while it goes down to around 5% in the case of siblings and even lower in half-siblings. This indicates susceptibility is partly polygenicallydriven.[1][4] It seems to be more common in some ethnic groups than others.[17]
Apart from familial studies, specific genes have been linked with MS. Differences in the human leukocyte antigen (HLA) system—a group of genes inchromosome 6 that serves as the major histocompatibility complex (MHC) in humans—increase the probability of suffering MS.[1] That changes in the HLA region are related to the susceptibility of an individual for MS has been known for over thirty years,[18] and additionally this same region has been implicated in the development of other autoinmmune diseases such as diabetes type I and systemic lupus erythematosus.[18] The most consistent finding is the association between multiple sclerosis and alleles of the MHC defined as DR15 and DQ6.[1] Other loci have shown a protective effect, such as HLA-C554 and HLA-DRB1*11.[1] Overall, it has been stimated that HLA changes accounts for between 20 and 60% of the genetic predisposition for MS.[18] Modern genetic methods (Genome-wide association studies, or GWAS) have also permitted to discover at least 12 other genes outside the HLA locus that modestly increase the probability of suffering MS.[18]

Environmental factors

Different environmental factors, both of infectious and non-infectious origin, have been proposed as risk factors for MS. Although some are partly modifiable, only further research—especially clinical trials—will reveal whether their elimination can help prevent MS.[19]
MS is more common in people who live farther from the equator, although many exceptions exist.[1] Decreased sunlight exposure has been linked with a higher risk of MS.[19] Decreased vitamin D production and intake has been the main biological mechanism used to explain the higher risk among those less exposed to sun.[19][20][21]
Severe stress may be a risk factor although evidence is weak.[19] Smoking has also been shown to be an independent risk factor for developing MS.[20]Association with occupational exposures and toxins—mainly solvents—has been evaluated, but no clear conclusions have been reached.[19]Vaccinations were investigated as causal factors for the disease; however, most studies show no association between MS and vaccines.[19] Several other possible risk factors, such as diet[22] and hormone intake, have been investigated; however, evidence on their relation with the disease is "sparse and unpersuasive".[20]
Gout occurs less than would statistically be expected in people with MS, and low levels of uric acid have been found in people with MS as compared to normal individuals. This led to the theory that uric acid protects against MS, although its exact importance remains unknown.[23]


Many microbes have been proposed as potential infectious triggers of MS, but none have been substantiated.[4] Moving at an early age from one location in the world to another alters a person's subsequent risk of MS.[5] An explanation for this could be that some kind of infection, produced by a widespread microbe rather than a rare pathogen, is the origin of the disease.[5] There are a number of proposed mechanisms, including the hygiene hypothesis and the prevalence hypothesis. The hygiene hypothesis proposes that exposure to several infectious agents early in life is protective against MS, the disease being a response to a later encounter with such agents.[1] The prevalence hypothesis proposes that the disease is due to a pathogen more common in regions of high MS prevalence where in most individuals it causes an asymptomatic persistent infection. Only in a few cases and after many years does it cause demyelination.[5][24] The hygiene hypothesis has received more support than the prevalence hypothesis.[5]
Evidence for viruses as a cause includes the presence of oligoclonal bands in the brain and cerebrospinal fluid of most people with MS, the association of several viruses with human demyelinationencephalomyelitis, and induction of demyelination in animals through viral infection.[25] Human herpes viruses are a candidate group of viruses linked to MS. Individuals who have never been infected by the Epstein-Barr virus have a reduced risk of having the disease, and those infected as young adults have a greater risk than those who had it at a younger age.[1][5] Although some consider that this goes against the hygiene hypothesis, since the noninfected have probably experienced a more hygienic upbringing,[5] others believe that there is no contradiction since it is a first encounter at a later moment with the causative virus that is the trigger for the disease.[1] Other diseases that have also been related with MS are measlesmumps, and rubella.[1]


Demyelination in MS. On Klüver-Barrera myelin staining, decoloration in the area of the lesion can be appreciated (Original scale 1:100).


MS is believed to be an immune-mediated disorder mediated by a complex interaction of the individual's genetics and as yet unidentified environmental insults.[4] Damage is believed to be caused by the person's own immune system attacking the nervous system. Possible targets of the immune response include myelin basic protein (MBP) and proteolipid protein (PLP). The commonly prescribed MS drug Copaxone was designed to mimic MBP and therefore act as a decoy for autoreactive immune cells. Even so, the role of MBP in MS is controversial; it is buried within the myelin sheath (rather than on the surface), where immune cells would not be able to recognize it.
Recent data suggest a role for myelin lipids in MS.[26] Historically, researchers have assumed the myelin target was a protein, even though the myelin sheath is nearly 80% lipid. Furthermore, lipids are known to be the target of another prominent nervous system autoimmune condition, Guillain-Barre Syndrome.
Whether the autoantigen is a protein or a lipid, autoimmunity may arise when immune cells recognizing a foreign antigen cross-react with self antigens. This process is known as molecular mimicry.[4][27]


The name multiple sclerosis refers to the scars (sclerae – better known as plaques or lesions) that form in the nervous system. MS lesions most commonly involve white matter areas close to theventricles of the cerebellumbrain stembasal ganglia and spinal cord; and the optic nerve. The function of white matter cells is to carry signals between grey matter areas, where the processing is done, and the rest of the body. The peripheral nervous system is rarely involved.[4]
More specifically, MS destroys oligodendrocytes, the cells responsible for creating and maintaining a fatty layer—known as the myelin sheath—which helps the neurons carry electrical signals(action potentials).[4] MS results in a thinning or complete loss of myelin and, as the disease advances, the cutting (transection) of the neuron's axons. When the myelin is lost, a neuron can no longer effectively conduct electrical signals.[4] A repair process, called remyelination, takes place in early phases of the disease, but the oligodendrocytes cannot completely rebuild the cell's myelin sheath.[28] Repeated attacks lead to successively fewer effective remyelinations, until a scar-like plaque is built up around the damaged axons.[28] Different lesion patterns have been described.[29]


Apart from demyelination, the other pathologic hallmark of the disease is inflammation. According to a strictly immunological explanation of MS, the inflammatory process is caused by T cells, a kind of lymphocyte. Lymphocytes are cells that play an important role in the body's defenses.[4] In MS, T cells gain entry into the brain via disruptions in the blood–brain barrier. Evidence from animal models also point to a role of B cells in addition to T cells in development of the disease.[30]
The T cells recognize myelin as foreign and attack it as if it were an invading virus. This triggers inflammatory processes, stimulating other immune cells and soluble factors like cytokines andantibodies. Further leaks form in the blood–brain barrier, which in turn cause a number of other damaging effects such as swelling, activation of macrophages, and more activation of cytokines and other destructive proteins.[4]

Blood–brain barrier breakdown

The blood–brain barrier is a part of the capillary system that prevents the entry of T cells into the central nervous system.[4] However, it may become permeable to these types of cells because of an infection or a virus.[4] When the blood–brain barrier regains its integrity, typically after the infection or virus has cleared, the T cells are trapped inside the brain.[4]


Multiple sclerosis can be difficult to diagnose since its signs and symptoms may be similar to other medical problems.[1][31] Medical organizations have created diagnostic criteria to ease and standardize the diagnostic process especially in the first stages of the disease.[1] Historically, the Schumacher and Poser criteria were both popular.[32]
Currently, the McDonald criteria focus on a demonstration with clinical, laboratory and radiologic data of the dissemination of MS lesions in time and space for non-invasive MS diagnosis, though some have stated that the only proved diagnosis of MS is autopsy, or occasionally biopsy, where lesions typical of MS can be detected through histopathological techniques.[1][33][34]
Clinical data alone may be sufficient for a diagnosis of MS if an individual has suffered separate episodes of neurologic symptoms characteristic of MS.[33] Since some people seek medical attention after only one attack, other testing may hasten and ease the diagnosis. The most commonly used diagnostic tools are neuroimaging, analysis of cerebrospinal fluid and evoked potentialsMagnetic resonance imaging of the brain and spine shows areas of demyelination (lesions or plaques). Gadolinium can be administered intravenously as a contrast to highlight active plaques and, by elimination, demonstrate the existence of historical lesions not associated with symptoms at the moment of the evaluation.[33][35] Testing of cerebrospinal fluid obtained from alumbar puncture can provide evidence of chronic inflammation of the central nervous system. The cerebrospinal fluid is tested for oligoclonal bands of IgG on electrophoresis, which are inflammation markers found in 75–85% of people with MS.[33][36] The nervous system of a person with MS responds less actively to stimulation of the optic nerve and sensory nerves due to demyelination of such pathways. These brain responses can be examined using visual and sensory evoked potentials.[37]

Clinical courses

Progression of MS subtypes
Several subtypes, or patterns of progression, have been described. Subtypes use the past course of the disease in an attempt to predictthe future course. They are important not only for prognosis but also for therapeutic decisions. In 1996 the United States National Multiple Sclerosis Society standardized four clinical courses:[7]
  1. relapsing remitting,
  2. secondary progressive,
  3. primary progressive, and
  4. progressive relapsing.
The relapsing-remitting subtype is characterized by unpredictable relapses followed by periods of months to years of relative quiet (remission) with no new signs of disease activity. Deficits suffered during attacks may either resolve or leave sequelae, the latter being more common as a function of time.[1] This describes the initial course of 80% of individuals with MS.[1] When deficits always resolve between attacks, this is sometimes referred to as benign MS,[38] although people will still accrue some degree of disability in the long term.[1] On the other hand, the term malignant multiple sclerosis is used to describe MS patients who reach significant level of disability in a short period of time.[39] The relapsing-remitting subtype usually begins with a clinically isolated syndrome (CIS). In CIS, a person has an attack suggestive of demyelination, but does not fulfill the criteria for multiple sclerosis.[1][40] However only 30 to 70% of persons experiencing CIS later develop MS.[40]
Nerve axon with myelin sheath
Secondary progressive MS describes around 65% of those with an initial relapsing-remitting MS, who then begin to have progressive neurologic decline between acute attacks without any definite periods of remission.[1][7] Occasional relapses and minor remissions may appear.[7]The median time between disease onset and conversion from relapsing-remitting to secondary progressive MS is 19 years.[41] The primary progressive subtype describes the approximately 10–15% of individuals who never have remission after their initial MS symptoms.[42] It is characterized by progression of disability from onset, with no, or only occasional and minor, remissions and improvements.[7] The age of onset for the primary progressive subtype is later than for the relapsing-remitting, but similar to mean age of progression between the relapsing-remitting and the secondary progressive. In both cases it is around 40 years of age.[1]
Progressive relapsing MS describes those individuals who, from onset, have a steady neurologic decline but also suffer clear superimposed attacks. This is the least common of all subtypes.[7]
Atypical variants of MS with non-standard behavior have been described; these include Devic's diseaseBalo concentric sclerosisSchilder's diffuse sclerosis and Marburg multiple sclerosis. There is debate on whether they are MS variants or different diseases.[43] Multiple sclerosis also behaves differently in children, taking more time to reach the progressive stage.[1] Nevertheless they still reach it at a lower mean age than adults.[1]


Although there is no known cure for multiple sclerosis, several therapies have proven helpful. The primary aims of therapy are returning function after an attack, preventing new attacks, and preventing disability. As with any medical treatment, medications used in the management of MS have several adverse effectsAlternative treatments are pursued by some people, despite the shortage of supporting, comparable, replicated scientific study.

Acute attacks

During symptomatic attacks, administration of high doses of intravenous corticosteroids, such as methylprednisolone, is the routine therapy for acute relapses,[1] while oral corticosteroids seem to have a similar efficacy and safety profile.[44] Although generally effective in the short term for relieving symptoms, corticosteroid treatments do not appear to have a significant impact on long-term recovery.[45] Consequences of severe attacks which do not respond to corticosteroids might be treated by plasmapheresis.[1]

Disease-modifying treatments

Disease-modifying treatments are expensive and most of these require frequent (up-to-daily) injections. Others require IV infusions (pictured) at 1–3 month intervals.
Irritation zone after injection of glatiramer acetate.
As of April 2013, eight disease-modifying treatments have been approved by regulatory agencies of different countries. The approved drugs are interferon beta-1ainterferon beta-1bglatiramer acetatemitoxantronenatalizumabfingolimodteriflunomide and dimethyl fumarate.[1][46][47][48][49]
The interferons and glatiramer acetate are delivered by frequent injections, varying from once-per-day for glatiramer acetate to once-per-week (but intra-muscular) for interferon beta-1a. Natalizumab and mitoxantrone are given by intravenous (IV) infusion at monthly intervals in the case of natalizumab and every three months in the case of mitoxantrone.[50][51][52] In 2010 fingolimod became the first oral drug approved by the FDA,[46] being followed by teriflunomide and dimethyl fumarate.[47][48] Fingolimod and teriflunomide are taken through a daily single dose whereas dimethyl fumarate is administered twice daily.[47][48][53] Most drugs are approved only for the relapsing-remitting course (RRMS). Medications are modestly effective at decreasing the number of attacks in RRMS.[54]
Interferons and glatiramer acetate are roughly equivalent, reducing relapses by approximately 30%.[1] Comparisons to natalizumab show that the most effective is the latter, both in terms of relapse rate reduction and halting disability progression.[55] Mitoxantrone may be the most effective of them all; however, it is generally not considered as a long-term therapy, as its use is limited by severe secondary effects.[1][56] While more studies of the long-term effects of the drugs are needed,[1][56][57] specially for the newest treatments, existing data on the effects of interferons and glatiramer acetate indicate that early-initiated long-term therapy is safe and it is related to better outcomes.[57][58]
The earliest clinical presentation of RRMS is the clinically isolated syndrome (CIS). Treatment with interferons during an initial attack decreases the chance that a person will develop clinical MS.[1][59] Treatment of progressive MS is more difficult than relapsing-remitting MS. Mitoxantrone has shown positive effects in those with secondary progressive and progressive relapsing courses. It is moderately effective in reducing the progression of the disease and the frequency of relapses in short-term follow-up.[60] No treatment has been proven to modify the course of primary progressive MS.[61]Efficacy of most common treatments, interferons and glatiramer acetate, in early-onset MS (before eighteen years of age) has been estimated to be roughly equivalent to adults.[62]
As with many medical treatments, these treatments have several adverse effects. One of the most common is irritation at the injection site for glatiramer acetate and the interferon treatments. Over time, a visible dent at the injection site, due to the local destruction of fat tissue, known as lipoatrophy, may develop. Interferons produce symptoms similar to influenza;[63] some people taking glatiramer experience a post-injection reaction manifested by flushing, chest tightness, heart palpitations, breathlessness, and anxiety, which usually lasts less than thirty minutes.[64] More dangerous but much less common are liver damage from interferons,[65] severe cardiotoxicityinfertility, and acute myeloid leukemia of mitoxantrone,[1][56] and the putative link between natalizumab and some cases of progressive multifocal leukoencephalopathy.[1]
Fingolimod may give rise to hypertension and bradycardiamacular edema, elevated liver enzymes or reduction in lymphocite levels.[66] Teriflunomide is considered a very safe drug. Nevertheless there have been reports of liver failure and PML and it is dangerous for fetal development.[66] Most common secondary effects of dimethyl fumarate are flushing and gastrointestinal problems.[48] While dimethyl fumarate leads to a reduction in white blood cell count there were no reported cases of opportunistic infections during clinical trials.[48]

Associated symptoms

Disease-modifying treatments reduce the progression rate of the disease, but do not stop it. As multiple sclerosis progresses, the symptomatology tends to increase. The disease is associated with a variety of symptoms and functional deficits that result in a range of progressive impairments and disability. Management of these deficits is therefore very important. Both drug therapy and neurorehabilitation have shown to ease the burden of some symptoms, though neither influences disease progression.[1][67] Some symptoms have a good response to medication, such as unstable bladder and spasticity, while management of many others is much more complicated.[1] As for any person with neurologic deficits, amultidisciplinary approach is key to improving quality of life; however, there are particular difficulties in specifying a 'core team' because people with MS may need help from almost any health profession or service at some point.[1] Multidisciplinary rehabilitation programs increase activity and participation of people with MS but do not influence impairment level.[68] Due to the paucity of randomized controlled studies, there is limited evidence of the overall efficacy of individual therapy disciplines,[69][69][70] though there is good evidence that specific approaches, such as exercise,[71][72] psychology therapies, particularly cognitive behavioral approaches[73] and energy conservation instruction[74] are effective.

Alternative treatments

Over 50% of MS patients may use complementary and alternative medicine, although numbers vary greatly depending on the definition of alternative medicine used.[75] The evidence for effectiveness for such treatments in most cases is weak or absent.[75][76] Examples of treatments used by patients with unproven efficacy are dietary supplementation and regimens,[75][77]relaxation techniques such as yoga,[75] herbal medicine (including the use of medical cannabis),[75][78] hyperbaric oxygenation,[79] self-infection with hookworm (known generally as helminthic therapy), reflexology or acupunture.[75][80] Regarding the characteristics of users, they are more frequently women, have had MS for a longer time and tend to be more disabled. Moreover, they also have lower levels of satisfaction with conventional healthcare.[75]


Disability-adjusted life year for multiple sclerosis per 100,000 inhabitants in 2004
  no data
The prognosis (the expected future course of the disease) for a person with multiple sclerosis depends on the subtype of the disease; the individual's sex, age, and initial symptoms; and the degree of disability the person experiences.[8] The disease evolves and advances over decades, 30 being the mean years to death since onset.[1]
Female sex, relapsing-remitting subtype, optic neuritis or sensory symptoms at onset, few attacks in the initial years and especially early age at onset, are associated with a better course.[8][81]
The life expectancy of people with MS is 5 to 10 years lower than that of unaffected people.[1] Almost 40% of people with MS reach the seventh decade of life.[81] Nevertheless, two-thirds of the deaths in people with MS are directly related to the consequences of the disease.[1] Suicide also has a higher prevalence than in the healthy population, while infections and complications are especially hazardous for the more disabled ones.[1]
Although most people lose the ability to walk before death, 90% are still capable of independent walking at 10 years from onset, and 75% at 15 years.[81][82]


Two main measures are used in epidemiological studies: incidence and prevalence. Incidence is the number of new cases per unit of person–time at risk (usually number of new cases per thousand person–years); while prevalence is the total number of cases of the disease in the population at a given time. Prevalence is known to depend not only on incidence, but also on survival rate and migrations of affected people. MS has a prevalence that ranges between 2 and 150 per 100,000 depending on the country or specific population.[2] Studies on populational and geographical patterns of epidemiological measures have been very common in MS,[24] and have led to the proposal of different etiological (causal) theories.[5][19][20][24]
MS usually appears in adults in their thirties but it can also appear in children.[1] The primary progressive subtype is more common in people in their fifties.[42] As with many autoimmune disorders, the disease is more common in women, and the trend may be increasing.[1][83] The CDC data suggest that MS is three times more common in women than in men in the United States.[84] In children, the sex ratio difference is higher,[1] while in people over fifty, MS affects males and females almost equally.[42]
There is a north-to-south gradient in the northern hemisphere and a south-to-north gradient in the southern hemisphere, with MS being much less common in people living near the equator.[1][83]Climatesunlight and intake of vitamin D have been investigated as possible causes of the disease that could explain this latitude gradient.[20] However, there are important exceptions to the north–south pattern and changes in prevalence rates over time;[1] in general, this trend might be disappearing.[83] This indicates that other factors such as environment or genetics have to be taken into account to explain the origin of MS.[1] MS is also more common in regions with northern European populations.[1] But even in regions where MS is common, some ethnic groups are at low risk of developing the disease, including the SamisTurkmenAmerindians, Canadian Hutterites, Africans, and New Zealand Māori.[85]
Environmental factors during childhood may play an important role in the development of MS later in life. Several studies of migrants show that if migration occurs before the age of 15, the migrant acquires the new region's susceptibility to MS. If migration takes place after age 15, the migrant retains the susceptibility of his home country.[1][19] However, the age–geographical risk for developing multiple sclerosis may span a larger timescale.[1] A relationship between season of birth and MS has also been found which lends support to an association with sunlight and vitamin D. For example fewer people with MS are born in November as compared to May.[86]


Medical discovery

Detail of Carswell's drawing of MS lesions in the brain stem and spinal cord(1838)
The French neurologist Jean-Martin Charcot (1825–1893) was the first person to recognize multiple sclerosis as a distinct disease in 1868.[87]Summarizing previous reports and adding his own clinical and pathological observations, Charcot called the disease sclerose en plaques. The three signs of MS now known as Charcot's triad 1 are nystagmusintention tremor, and telegraphic speech (scanning speech), though these are not unique to MS. Charcot also observed cognition changes, describing his patients as having a "marked enfeeblement of the memory" and "conceptions that formed slowly".[3]
Before Charcot, Robert Carswell (1793–1857), a British professor of pathology, and Jean Cruveilhier (1791–1873), a French professor of pathologic anatomy, had described and illustrated many of the disease's clinical details, but did not identify it as a separate disease.[87] Specifically, Carswell described the injuries he found as "a remarkable lesion of the spinal cord accompanied with atrophy".[1] Under the microscope, Swiss pathologist Georg Eduard Rindfleisch (1836–1908) noted in 1863 that the inflammation-associated lesions were distributed around blood vessels.[88][89]
After Charcot's description, Eugène Devic (1858–1930), Jozsef Balo (1895–1979), Paul Ferdinand Schilder (1886–1940), and Otto Marburg (1874–1948) described special cases of the disease. During all the 20th century there was an important development on the theories about the cause and pathogenesis of MS while efficacious treatments began to appear in 1990.[1]

Historical cases

There are several historical accounts of people who lived before or shortly after the disease was described by Charcot and probably had MS.
A young woman called Halldora who lived in Iceland around 1200 suddenly lost her vision and mobility but, after praying to the saints, recovered them seven days after. Saint Lidwina of Schiedam (1380–1433), a Dutch nun, may be one of the first clearly identifiable MS patients. From the age of 16 until her death at 53, she suffered intermittent pain, weakness of the legs, and vision loss—symptoms typical of MS.[90] Both cases have led to the proposal of a 'Viking gene' hypothesis for the dissemination of the disease.[91]
Augustus Frederick d'Este (1794–1848), son of Prince Augustus Frederick, Duke of Sussex and Lady Augusta Murray and the grandson of George III of the United Kingdom, almost certainly suffered from MS. D'Este left a detailed diary describing his 22 years living with the disease. His diary began in 1822 and ended in 1846, although it remained unknown until 1948. His symptoms began at age 28 with a sudden transient visual loss (amaurosis fugax) after the funeral of a friend. During the course of his disease, he developed weakness of the legs, clumsiness of the hands, numbness, dizziness, bladder disturbances, and erectile dysfunction. In 1844, he began to use a wheelchair. Despite his illness, he kept an optimistic view of life.[92][93]
Another early account of MS was kept by the British diarist W. N. P. Barbellionnom-de-plume of Bruce Frederick Cummings (1889–1919), who maintained a detailed log of his diagnosis and struggle with MS.[93] His diary was published in 1919 as The Journal of a Disappointed Man.[94]


There have been important advances in the research of multiple sclerosis in the last decade that have led to a deeper comprenhension of the disease mechanisms and also to more effective treatments.[95] Nevertheless, MS continues to be an active field of research.[95]

Diagnosis and disease biomarkers

Magnetic resonance imaging brain scan produced using a Gradient-echo phase sequence. It shows an iron deposition in an existing white matter lesion (inside green box in the middle of the image; enhanced and signaled with red arrow at top-left hand side corner). This and other imaging techniques are still under development.[96]
Regarding diagnosis it is not expected that diagnostic criteria may change in the near future. On the other hand, while the search for biomarkers of the disease that may aid diagnosis, prediction of disease evolution,or evaluation of disease evolution, is intense there are not any expected breakthroughs in the short term.[95]
The variable clinical presentation of MS and the lack of diagnostic laboratory tests lead to delays in diagnosis and the impossibility of predicting diagnosis. New diagnostic methods that are being investigated include work with anti-myelin antibodies, and studies with serum and cerebrospinal fluidbut none of them has yielded reliable positive results.[97]
Currently there are no clinically established laboratory investigations available that can predict prognosis. However, several promising approaches have been proposed. Investigations on the prediction of evolution have centered on monitoring disease activity. Disease activation biomarkers includeinterleukin-6nitric oxide and nitric oxide synthaseosteopontin, and fetuin-A.[97] On the other hand since disease progression is the result of neurodegeneration the roles of proteins indicative of neuronalaxonal, and glial loss such as neurofilamentstau and N-acetylaspartate are under investigation.[97] A final investigative field is work with biomarkers that distinguish between medication responders and nonresponders.[97]
The improvement in neuroimaging techniques such as positron emission tomography (PET) or magnetic resonance imaging (MRI) carry a promise for better diagnosis and prognosis predictions, albeit the effect of such improvements in daily medical practice may take several decades.[95] Regarding MRI, there are on the one hand several techniques that have already shown some usefulness in research settings and could be introduced into clinical practice, such as double-inversion recovery sequences, magnetization transferdiffusion tensor, or functional magnetic resonance imaging.[98] These techniques have a higher pathological specificity than existing ones, but still lack some development including standarization of acquisition protocols and the creation of normative values.[98] On the other hand, there are also several techniques under development that could be useful.[98] These include the use of new contrast agents capable of measuring levels of peripheral macrophages, inflammation, or neuronal dysfunction.[98] Other techniques may quantify iron deposition and could serve to evaluate the role of this pathological feature in MS, or cerebral perfusion, which is known to be altered in patients.[98] Similary new PET radiotracers might serve as markers of altered proccessess in MS such as brain inflammation, cortical pathology,apoptosis, or remylienation.[99]

Clinical measures of evolution

The main measure of evolution of symptoms, specially important as an endpoint in MS trials, is the EDSS. However, this and other measures used in clinical studies are far from perfect and suffer from insetiveness or inadequate validation.[100] In this sense there is ongoing research to improve the EDSS and other measures such as the Multiple Sclerosis Functional Composite. This is specially important at the current state of research where the greater efficacy of existing medications force functional measures in clinical trials to be highly sensitive in order to adequately measure disease changes.[100]


Progress in the field of genetics has been outstanding in the last two decades with highly improved methods and cheaper tests. These advances have in turn led to a greater understanding of the genetic component of MS. This trend is expected to continue, raising the possibility of discovering key mechanisms implicated in the disease. However, it is hard to predict how this future discoveries will impact in the clinical practice or in the research for new drugs and treatments.[95]
An example of a soon-to-be finished study is the Wellcome Trust case control consortium, a massive collaboration study including 120,000 genetic samples, of which 8000 are from individuals with MS.[18] This study may presummibly identify all the common genetic variants involved in MS.[18] Further studies will probably involve full genome sequencing of large samples, or the study of structural genetic variants such as insertionsdeletions or polymorphisms.[18]


Chemical structure of alemtuzumab
Research directions on MS treatments include investigations of MS pathogenesis and heterogeneity; research of more effective, convenient, or tolerable new treatments for RRMS; creation of therapies for the progressive subtypes; neuroprotection strategies; and the search for effective symptomatic treatments.[101]
Advances during the last decades has led to the recent approval of several oral drugs. These drugs are expected to gain in popularity and frequency of use at the expense of previously existing therapies.[95] Further oral drugs are still under investigation, the most notable example being laquinimod, which was announced in August 2012 to be the focus of a third phase III trial after mixed results in the previous ones.[102] Similarly, Other studies are aimed to improve efficacy and ease of use of already existing therapies through the use of novel preparations. Such is the case the PEGylated version of interferon-β-1a, that has a longer life than normal interferon and therefore it is being studied if given at less frequent doses has a similar efficacy than the existing product.[103][104] Request for approval of peginterferon beta-1a is expected during 2013.[104]
Monoclonal antibodies, which are drugs of the same family as natalizumab, have also raised high levels of interest and research. Alemtuzumab,daclizumab and CD20 monoclonal antibodies such as rituximabocrelizumab and ofatumumab have all shown some benefit and are under study as potential treatments for MS.[105] Nevertheless their use has also been accompanied by the appearance of potentially dangerous adverse effects, most importantly opportunistic infections.[95] Related to these investigations is the recent development of a test against JC virus antibodies which might help to predict what patients are at a greater risk of developing progressive multifocal leukoencephalopathy when taking natalizumab.[95] While monoclonal antibodies are probably going to have some role in the treatment of the disease in the future, it is believed that it will be small due to the risks associated to them.[95]
Another research strategy is to evaluate the combined effectiveness of two or more drugs.[106] The main rationale for polytherapy in MS is that the involved treatments target different mechanisms of the disease and therefore their use is not necessarily exclusive.[106] Moreover synergies, in which a drug potentiates the effect of another are also possible. Nevertheless there can also appear important drawbacks such as antagonizing mechanisms of action or potentiation of deleterious secondary effects.[106] While there have been several clinical trials of combined therapy none has shown positive enough effects to merit the consideration as a viable treatment for MS.[106]
Finally, regarding neuroprotective and specially regenerative treatments, such as stem cell therapy, while their research is considered of high importance at the moment they are only a promise of future therapeutic approaches.[107] Likewise, there are not any effective treatments for the progressive variants of the disease. Many of the newest drugs as well as those under development are probably going to be evaluated as therapies for PPMS or SPMS, and their improved effectiveness when compared with previously existing drugs may eventually lead to a positive result in these groups of patients.[95]

Chronic cerebrospinal venous insufficiency

In 2008, vascular surgeon Paolo Zamboni suggested that MS involves a vascular process he referred to as chronic cerebrospinal venous insufficiency (CCSVI), in which veins from the brain are constricted. He found CCSVI in all patients with MS in his study, performed a surgical procedure, later called in the media "liberation procedure" to correct it and claimed that 73% of participants improved.[108] This theory received important attention in the media and among MS patients, specially in Canada.[109] Concern has been raised with Zamboni's research as it was neither blinded nor controlled, and additionally its assumptions about the pathophisiology of the disease may not be backed by known data.[110] Also further studies have either not found a relationship or found a much less strong one.[111] This has raised serious objections to the hypothesis of CCSVI originating MS.[112] The "liberation procedure" has been criticized for possibly resulting in serious complications and deaths while its benefits have not been proven.[110] Currently it is recommended not to use the proposed treatment unless its effectiveness is confirmed by controlled studies.[113] Research on CCSVI has been fast tracked but researchers have been unable to confirm whether CCSVI has a role in causing MS.[111]

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