Why do some HNPP results appear negative?

Jul 26, 2017 suswatibasu1 Comment

Genetic testing for HNPP can be daunting, mostly because it can be a confirmation of all your worst fears. At the same time, it can come as a relief for many, as it marks the start of an official journey. But what happens when your results turn up negative?

As the NHS website explains, we need two peripheral myelin protein-22 (PMP22) genes, one from each parent, for the normal development of the peripheral nerves. These genes provide instructions for the creation of PMP22 protein, which makes up the protective outer layer of each nerve. This outer layer, which is a bit like the plastic coating that insulates a wire, is called myelin.

“It would have been nice to feel the immediate gratification of a positive HNPP test result. It would have answered nearly every question I had about what was happening to my body.”

From the Girl With A Purple Cane blog

In HNPP, one copy of the PMP22 gene is lost (deleted) so that people have only one copy of this gene. A person with HNPP will have inherited a faulty copy of the PMP22 gene from one of their parents.

With only one normal PMP22 gene, their myelin is fragile and more susceptible to injury. Just the slightest pressure, stretch or repetitive movement on the nerve causes sections of the myelin to be lost. Signals cannot be relayed to and from the muscles properly.

A genetic test usually confirms whether one of the copies is deleted. Around 80 per cent of cases of HNPP is down to deletions of this particular gene. However, in some cases even with a genetic test, it can come back negative.

According to DNA diagnostic experts GeneDx, genetic diagnosis is identified in approximately 50-70 per cent of individuals with the hereditary neuropathic condition Charcot-Marie-Tooth disease, which shows that even if the symptoms present themselves, they may not be explicitly diagnosed for all.

This was seen in a 2006 study where a 32-year-old woman diagnosed with CMT, where the PMP22 genes are duplicated, came back with a false negative even though she had two different types of gene mutations.

gene testing HNPP hereditary neuropathy — Algorithm for Peripheral Neuropathy testing – *GeneDx*

What happens if the results are positive?

A positive result indicates that a disease-causing mutation was identified in the individual who was tested. In this case, you can get predictive genetic testing in terms of planning ahead as well as testing for your family. They can then go ahead for further evaluation. There can be variability in symptoms, age of onset, and disease severity even among members of the same family who have the same genetic mutation.

What if the results are negative?

Even with a negative test result, it does not rule out that a person with neuropathy does not have a genetic condition. As the diagnostic company suggests possible reasons for a negative result could be:

The patient has a mutation in a gene not included in the testing panel
The patient may have a mutation in a part of a neuropathy gene that was not covered by the test
The patient does not have hereditary type of neuropathy

As Sharon Plon, Medical Geneticist and Director of MD-PhD program at Baylor College of Medicine, says:

@splon this form of CMT can be confused with myopathies so CMT hadn't been considered.

— Sharon Plon (@splon) September 27, 2013

Unknown results

In some cases, results may not conclusive either way. These results are referred to as variant of unknown clinical significance (VUS). This indicates that the role of the genetic change in causing neuropathies has not clearly been established. In some cases, testing of other family members may help clarify the clinical significance of a VUS. The greater the number of affected family members who carry the VUS, the greater the likelihood that the identified variant is hereditary.

In other instances, if the person is the only one identified with a single mutation, they may be a heterozygous carrier i.e. they inherit a pair of genes where one is dominant and one is recessive.

Advantages of getting a panel test if negative

Higher diagnostic rate
- all ‘common’ genes in one test
- the rare genes included/ genes that no diagnostic service is available
- more patients and families to get a genetic diagnosis
Faster turn around time
- all genes in one test, not sequential testing
Familial cases can avoid further clinical investigations
Enhance our knowledge and understanding for IPN genes (Enrich for fragments of interest)
- routine testing of rare genes
- interaction between genes/ modifying mutations
Cost savings
- directly: panel testing is cost effective
- indirectly: faster result / high diagnostic rate can lead to reduced
- appointments and other investigations for patient and family

However, the cost of a genetic test depends on the complexity of the test and can range from under £100 to £1000s, for example a basic chromosome test (karyotype) would cost about £150 and screening a panel of 108 genes associated with congenital cateracts costs £1100. The cost increases if more than one test is necessary or if multiple family members need to be tested. So it can be a hefty investment depending on where you’re getting it done.

The problems with certain gene tests

Either way, as some research states, the CMT1A duplication was identified more frequently than the HNPP deletion, suggesting some types of gene variants are more difficult to detect to than others such as those for HNPP.

The study, Charcot-Marie-Tooth Disease And Related Hereditary Polyneuropathies featured in the Genetics in Medicine journal, says: “HNPP can mimic multifocal neuropathy, a frequently inflammatory disorder that requires immunosuppressant therapy.

“Molecular testing occasionally identifies new sequence variations of unknown pathogenic significance. In these cases further studies (segregation analysis, functional assay) are required to establish pathogenicity, which are performed in research laboratories.”

Hence there is still quite a lot of testing to be done to perfect the current sequencing method. So hopefully it won’t come as a shock if your results turn out to be negative, but be prepared for that eventuality.

Is surgery worth it with HNPP?

Jul 23, 2017Jul 23, 2017 suswatibasu4 Comments

Carpal tunnel syndrome seems to be a common occurrence with many HNPP sufferers, and the symptoms sometimes overlap when it comes to nerve damage around the wrists. Not to mention, foot issues such as high arches and unstable ankles appear for some with this particular condition. And the obvious question for those newly-diagnosed tends to be can surgery help stop or relieve the symptoms?

Most people with HNPP have attacks of numbness, tingling and muscle weakness in the leg or foot, which can make walking, climbing stairs and driving difficult or impossible, and can result in foot drop – the inability to lift the front part of the foot because of muscle weakness.

While others can simultaneously have weakness in the elbow, wrist or hands, which can result in wrist drop and loss of sensation in the index finger and thumb (symptoms similar to those of carpal tunnel syndrome), making fine movements such as fastening buttons, typing and gripping impossible.

Disclaimer: Please ask your medical practitioner or doctor for more information. This article is based on various research, journals and testimonies.

What is carpal tunnel syndrome?

Carpal tunnel syndrome or CTS is a common condition that causes a tingling sensation, numbness and sometimes pain in the hand and fingers. These sensations usually develop gradually and start off being worse during the night. They tend to affect the thumb, index finger and middle finger.

The symptoms of CTS also tend to develop gradually, and usually start off being worse at night or early in the morning.

Any repetitive actions of the hand or wrist can aggravate the symptoms, as can keeping your arm or hand in the same position for a prolonged period of time.

Symptoms include:

A dull ache and discomfort in the hand, forearm or upper arm
A burning, prickling sensation (paraesthesia) in the hand similar to pins and needles
Dry skin, swelling or changes in the skin colour of the hand becoming less sensitive to touch (hypoaesthesia)
Weakness and wasting away (atrophy) of the muscles at the base of the thumb
Pain may spread from your hand up to your forearm and elbow.

CTS ends up becoming a symptom of HNPP, as muscle strain isn’t the cause, rather nerve issues present itself in the form of carpal tunnel syndrome.

Will CTS surgery help?

The problem with getting surgery for CTS is that it may relieve symptoms in the short term, but evidence suggests that it is likely to return after a period of time. A study for The Musculoskeletal Journal of Hospital for Special Surgery presented a 38-year-old HNPP sufferer with complaints of numbness in the first three digits of both hands and weakness of both hands after doing yoga. She was seen by a hand surgeon after wrist splints and anti-inflammatories had no benefit.

“The doctor told me I would have instant relief, which I did. My recovery time about 3 weeks. Disadvantages: I lost 30% strength in my right hand.”

Case from Inspire Forum for Charcot-Marie Tooth

Ten weeks after the diagnosis, she underwent carpal tunnel and Guyon’s canal (surgery to decompress the ulnar nerve) releases, which yielded significant improvement in symptoms within a week. However, after several years, the symptoms returned and instead her hand was left permanently weakened by the surgery.

The authors of the report conclude: “Typically, carpal tunnel release is of little benefit, and ulnar nerve transposition at the elbow may worsen symptoms.

“However, in cases with severe symptoms, debility, and/or deformity, surgical intervention should be considered on an individual basis and in this patient appears to have been beneficial.”

This shows that surgery should be undertaken on a case by case basis. So you really need to weigh up your options, as it may relieve pain now, but create issues at a later stage.

Another case study featured in the report Is Carpal Tunnel Warranted for HNPP? also warned about having multiple surgeries. Authors Nicholas Earle and Douglas W. Zochodne conducted extensive research on the role of carpal tunnel decompression surgery for those with HNPP.

“[We] do not recommend multiple decompression procedures in an attempt to modify the natural history of HNPP.”

Is carpal tunnel decompression warranted for HNPP?
Nicholas Earle and Douglas W. Zochodne 2013

Two patients with HNPP underwent nerve decompression and surgery for CTS. Despite seeing some improvements, there were issues during surgery for one of the patients in terms of symptoms of HNPP posing itself.

The authors state that even though carpal tunnel decompression could be offered to patients who have “appropriate, persistent, and significant symptoms”, they add: “we do not recommend multiple decompression procedures in an attempt to modify the natural history of HNPP”.

Surgery for anyone increases the risk of nerve damage, from lying still. Individuals with HNPP are at a much greater risk. Nevertheless, knowing about the susceptibility to pressure palsies can help the surgical team avoid causing them by positioning you to avoid pressure palsies.

Correcting foot deformities

I do feel uncomfortable with the word ‘deformity’ but I’ll use this to describe the next lot of symptoms.

It is more common for those with hereditary neuropathies such as Charcot Marie-Tooth disorder, to undergo operations to correct the positioning of a foot. Clawed toes can be straightened, high arched feet can be flattened, and unstable ankles can be tightened.

For some people with HNPP, the toes begin to claw, causing pain on the ball of the foot, which develops as the deformity places downward pressure on the heads of the metatarsal bone and the protective fat pad beneath them is pulled away by the upturning toes.

Walking becomes painful and wearing shoes becomes difficult, hence many wear cushioned orthotics and special insoles to help alleviate symptoms. Over time, the deformity becomes fixed and conservative treatment no longer helps.

Foot drop, however, is more frequent as Glenn Pfeffer, MD, is the Director of the Foot and Ankle Center at Cedars-Sinai Medical Center reports. In an interview to the Hereditary Neuropathy Foundation, Dr Pfeffer says the muscles that lift up the foot and ankle weakens due to motor nerve issues, eventually causing the foot to drop. While it isn’t a long term solution, the doctor says surgery for patients with CMT and foot drop has “made great advances in the past decade”. But he only recommends surgery after conservative measures such as stretches, physiotherapy, as well as orthotics no longer work.

On a CMT UK forum on Health Unlocked, one person had undergone surgery for foot drop, consisting of four operations and then two subsequent procedures. The online user said: “Weigh up how much of handicap it is now, how much does it hurt and ask your surgeon about the long term future of your foot.”

While others have had more positive outcomes, with another netizen, who had high arches corrected, saying: “Was so incredible. It was life changing for me.”

Either way, whatever you choose to do, it’s important to also remember to provide your medical practitioner, surgeons, nurses and anyone involved with details of your condition, as you may need to have special positioning during surgery.

During surgery

In the Journal of Association of Anaesthetists of Great Britain and Ireland, a case of a woman with HNPP, who underwent a biopsy under general anaesthesia, was left with weakness and decreased sensation of her left arm due to incorrect positioning.

The study added that approximately 16 per cent of all anaesthesia-related claims in the United States was down to peripheral nerve injuries. The ulnar nerve is damaged most commonly (0.33 per cent of general anaesthetics); this is three times as common as injury to other nerves. Hence it is essential that you let your medical team know about your condition well in advance.

In the end, it is your choice if you want to go ahead with surgery, but the more knowledge you have beforehand on what to expect, the better the decision you will make and the outcome will be.

HNPP · Mental Health · Physical Health

Dealing with genetic testing with HNPP

Jul 22, 2017Jul 22, 2017 suswatibasu4 Comments

Getting genetically tested can be traumatic depending on the outcome, but for many it is a necessity. The uncertainty of not knowing for either yourself or your family can be a harrowing experience, but what comes next may appear to be more difficult. However, a diagnosis for HNPP can help explain how conditions are inherited, in order to help draw up medical management plans and discuss further family planning options.

“There are no right answers, there are simply decisions.”

Asked on the Inspire Forum for Inherited Neuropathy

The psychological effect of a genetic disorder can vary by the nature of the condition and the relationship of a person to the affected individual. Every family is different and it is difficult to predict how people will react to a genetic diagnosis. It’s helpful to think in advance about some of the possible reactions, though, so you can react quickly and minimise distress.

Disclaimer: Please ask your medical practitioner or doctor for more information. This article is based on various research, journals and testimonies.

The following information has been taken from Understanding Genetics: A New England Guide for Patients and Health Professionals:

Patients

A genetic diagnosis can be a great relief to the person suffering from the condition. It helps HNPP sufferers understand their disorder, especially when the condition is rare and the patient has struggled to find a diagnosis. Patients often spend years living with a condition without knowing its name or cause. Diagnoses usually lead to improved treatment options and access to support services. They can also help other family members make decisions about their own lives.

However, a genetic diagnosis may lead to negative reactions, too. The science of genetics can be confusing, and sufferers are often frustrated until they understand the nature of their condition. Anyone identified with a mutation may consider themselves at fault or interpret their diagnoses as leading to something they cannot fight. A genetic diagnosis can lead to fears about insurance and employment discrimination.

The reaction to a diagnosis varies from individual to individual.

Parents

Understandably, the diagnosis of a genetic condition may put stress on a relationship. Couples with an affected child often face difficult family planning decisions because future children may be at higher risk. Depending on the condition, parents may also be faced with hard choices regarding prenatal testing. It can also put a strain on relationships some times causing a communication breakdown. The magnitude of these decisions and their outcomes has an impact on the individuals involved and on their relationship.

Family

Unaffected family members should not be forgotten in the case of a genetic disorder. When one family member is diagnosed with a mutation, family members who do not have the mutation often feel guilt that loved ones are affected when they are not.

“When my daughter was in junior high, she told me that if it’s hereditary, it was my responsibility to figure it out. I’ve had various inconclusive genetic tests but am hopeful this next one will pinpoint it. The info won’t affect me in any way, but maybe generations from now, it could be life-changing.”

Asked on the Inspire Forum for Inherited Neuropathy

Siblings of children with special needs sometimes feel neglected because parents need to focus more time and effort on their siblings. Including unaffected family members in the planning of care for individuals with genetic conditions can help them come to grips with their own emotional issues.

Adults who are diagnosed with a genetic condition and are considering having a child will need to consider the risk of having an affected child as well as their ability to care for the child.

Genetic test results are often complex and may be difficult for patients and their families to understand. In some cases, a genetic test may reveal the risk status of other family members who may not wish to know this information, potentially encroaching upon their autonomy or privacy.

In general, support or advocacy groups and community resources can provide ongoing support to patients and their families with genetic conditions. Support groups provide a forum for sharing experiences about caring for a family member affected with a genetic condition, coping with a new diagnosis, obtaining healthcare or other services, and healing. Members of support groups know first-hand what it means to be faced with a diagnosis and to need accurate, up-to-date information. Staying connected with their community helps individuals fight the feelings of isolation that often surround families living with a genetic condition.

That being said, knowing what to expect during the testing process can help to prepare for what’s to come.

How to prepare for a genetic appointment

There are several things it is helpful to consider and find out before your genetic appointment, these include:

Take questions with you – Thinking through your concerns and queries in advance and writing them down to take with you
Check where the appointment will be – Genetic centres can be based in clinics across different hospitals so double-check with your hospital
Give details of other family member’s genetic diagnosis – If another member of your family has previously been seen in the genetic clinic, please let the clinic know their name and date of birth before your appointment. This will help them link the family information and will save time at your appointment.
Gather as much information about your family history – You are likely to be asked for this in your appointment. Clinics usually only ask about your family history as far back as grandparents.
If you want someone else tested who isn’t present – If your concern is about a genetic diagnosis affecting another member of the family, the clinic will need to get confirmation of the diagnosis. You may be asked to pass a consent form to your relative before your appointment.
Ask for help if you need additional assistance – It is very helpful to let the clinic know in advance.

What does an appointment involve and what happens after?

You will be seen by a clinical geneticist or a genetic counsellor, or both, depending on the reason you have been referred.
Your medical and family history will be taken.
If needed, you/your child will be examined by the doctor.
Where a diagnosis is known, you will be provided with information about the condition including an explanation of how it is inherited and what this may mean for you and other members of your family.
Options around genetic testing and family planning will be discussed if appropriate.
Support will be offered around decisions that need to be made
If genetic testing is available and you wish to go ahead with this, then you may have a blood sample taken.
Following your appointment it is likely you will be sent a letter summarising the information discussed.
You may only need to attend the clinic once or several appointments may be needed. You will be told at your appointment whether you need to be seen again.
If you had a blood sample taken for genetic testing, you should be told when to expect the results and agree a plan for how you will receive these.
Some types of results are always given in person in the clinic or by letter.

What next?

Genetic counselling – this involves a healthcare professional talking to you about a genetic condition or possible genetic condition affecting you, your child or another member of your family. Another important aspect of genetic counselling is that it provides support with the emotional and family implications of a genetic disorder.
Be wary of information you find on the internet – The internet is a powerful tool for diagnosis and support but there is a lot of misinformation out there and some of the things you read might be frightening. Remember, genetic conditions can manifest themselves differently in different people – every one of us is unique.
Connect with other people – This is a great way to share advice and support one another.
Know your rights – Apart from coping with the emotional and medical issues related to a positive genetic test result, patients are often faced with life-changing decisions, especially when it comes to family planning and thinking about genetic testing for your children. But it’s also important to check where your genetic information is going and how it is being used so ask about it during your appointment.

To find out more information about genetic testing and counselling, here are some organisations that deal with this specifically:

HNPP · Medication

Side effects of medication for HNPP

Jul 20, 2017Jul 20, 2017 suswatibasu4 Comments

After discovering that suffering from a fever and chronic fatigue for the past two weeks was down to my medication left me feeling alarmed. So is it a case of the drugs don’t work – they just make you worse?

It is common for people with peripheral neuropathy to experience different degrees of pain. Hence it’s important to identify the type of pain medication that will work best for managing painful peripheral neuropathy symptoms, that also works with your body chemistry, and compliments other treatments.

Disclaimer: Please check with your doctor or practitioner before taking new medicines. Make sure you’re not allergic.

Differences between pain

Acute pain usually comes on suddenly and is caused by something specific. It is sharp in quality. Acute pain usually does not last longer than six months. It goes away when there is no longer an underlying cause for the pain.

Chronic pain is pain that is ongoing and usually lasts longer than six months. This type of pain can continue even after the injury or illness that caused it has healed or gone away. Pain signals remain active in the nervous system for weeks, months, or years. Some people suffer chronic pain even when there is no past injury or apparent body damage.

The following are the main types of medication that HNPP sufferers tend to use.

Amitriptyline

Amitriptyline is used for headaches and depression, as well as neuropathic pain. It reportedly provides pain relief in about 1 in 4 (25%) more people than does a placebo, and about 1 in 4 (25%) more people than placebo report having at least one adverse event, which may be troublesome, but probably not serious. The most common side effects, experienced by 5-15 per cent of people, include dizziness, drowsiness, dry mouth, nausea, sometimes insomnia and constipation. Apparently it is slow-acting so it can take around six to eight weeks to show any effect.

Duloxetine

Otherwise known as Cymbalta, is commonly used to treat bladder problems, depression as well as neuropathic pain. According to a study for the Cochrane Database of Systematic Reviews, most people taking duloxetine however will have at least one side effect. These are mostly minor and the most common are feeling sick, being too awake or too sleepy, headache, dry mouth, constipation or dizziness. About one in six people stop duloxetine because of side effects. Serious problems caused by duloxetine are very rare though some HNPP sufferers have reported muscle spasms with this medication.

Pregabalin

Branded under the name Lyrica is among the most commonly used to treat peripheral neuropathy and specifically HNPP. It can be used to treat epilepsy, headaches or anxiety. It is said to slow nerve impulses that may cause seizures and blocks nerve related pain. While most can take it with it no problems, some of the side effects include dizziness, extreme drowsiness, headache, dry mouth, peripheral oedema (accumulation of fluid causing swelling), weight gain, blurred vision, motor in coordination and ataxia (tremor or lack of muscle control) occurring in 1-10 per cent patients at lower doses.

Gabapentin

Commonly known by its brand name Neurontin, it falls into a class of drugs known as anti-convulsants – or drugs used to treat epileptic seizures as well as relieve nerve pain. Only 14 per cent of patients taking gabapentin for chronic neuropathic pain report meaningful relief, according to another report by the Cochrane Database of Systematic Reviews. In a recent study by an independent organisation looking at the effectiveness of gabapentin and other drugs for treatment of nerve pain, as few as one in ten patients experienced a reduction in pain.

Two of the most common side effects of gabapentin are fatigue and weight gain. Many report excessive sleepiness and difficulty functioning while taking gabapentin. Significant weight gain has also been reported among some taking the drug – although the risk is generally low.

A study by the University of Miami Department of Neurology found that weight gain is more common among high dose users. In their study of 28 patients taking over 3000 mg/day, 10 patients experienced weight gain of 10 per cent of their baseline weight. That being said, some HNPP’ers have found relief from it, so it’s important not to knock anything until you try it.

When dealing with pain, it is worth giving whatever you can a chance and working with your doctor to try different approaches so that you find the particular approach that is right for you, which brings you the benefits of pain relief, allows you to do more, and gives you the quality of life that you want.

HNPP · Physical Health

Should you take part in clinical trials for HNPP?

Jul 17, 2017Jul 17, 2017 suswatibasuLeave a comment

“Clinical trials” is phrase that’s always bandied about for illnesses such as cancer, and you may wonder what it actually is and whether it’s worth taking part. The use of human volunteers to collect data is not always for everyone. It is wrapped in the enigma of experimentation and feeling exploited. But what is it all about?

“Fear is a greater barrier than the reality.”

Robert L. Comis, M.D

The National Heart, Lung and Blood Institute, run by the US Health Department, describes a clinical trial as research studies that explore whether a medical strategy, treatment, or device is safe and effective for humans. These studies enable medical professionals to follow the best path for certain illnesses or groups of people. The NHLBI say: “Clinical trials produce the best data available for health care decision-making.”

So why are people reluctant to take part?

A survey by Harris Interactive, Inc., showed that of the patients who knew about clinical trials, 71 per cent still chose not to participate.

Uncertainty of treatment – Fear of being treated as a guinea pig and getting a placebo is the most common factor that pulls patients away from clinical trials. In fact, placebos are rarely used in cancer treatment trials, and never in lieu of standard treatment, according to Robert L. Comis, M.D., president of the Coalition of National Cancer Cooperative Groups and chairman of the Eastern Cooperative Oncology Group in Philadelphia. Ninety-seven percent said they were treated with dignity and respect, and received excellent or good quality care.
Worry about insurance – For our US friends, one in five participants were concerned that their insurance companies may not pay out. But for those who enrolled in clinical trials, 79 per cent said their insurance company ultimately paid for the care they received.
Uncertainty of results/adverse effects – People are afraid whether the new therapy will work to improve their health or worsen their disease. Although researchers cannot guarantee outcomes, patient safety is apparently top priority. Each trial has enforced oversight, and patients also have rights that help protect them. Currently participant’s right are protected by regulatory bodies like the Institutional Review Board (IRB) in the US, and Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. There will be an equivalent to your native country, usually through the government.
Inconveniences. Some people can’t commit to the time required to participate in a clinical trial. Others may find the available hours incompatible with their schedule. Travel is an issue for some, whether they’re unable to transport themselves or find a geographic location close enough. Other social and economic disadvantages contribute to some populations being underrepresented. Some trials even pay the participants for enrolling in a trial. However, FDA suggests people must learn thoroughly about the risks involved in a study before enrolling, and not get lured by the free treatment or money being offered.
Missed opportunities – Low enrolment is attributed to many factors and varies on a per study basis, but if more people knew about clinical trials there would certainly be more participation. One study found that only one in three US adults knew about clinical trials, of the 1,000 surveyed.

The NHLBI state: “The purpose of clinical trials is research, so the studies follow strict scientific standards. These standards protect patients and help produce reliable study results.”

But does that ease our fears?

To be fair, it’s unusual for clinical trials to try something completely experimental. They usually go through a lot of scientific research before getting to this stage. That being said it is important to check the credentials if you do wish to take part.

It is one of the final stages of a long and careful research process. The process often begins in a laboratory, where scientists first develop and test new ideas.

If an approach seems promising, the next step may involve animal testing. This shows how the approach affects a living body and whether it’s harmful. However, an approach that works well in the lab or animals doesn’t always work well in people. Hence, research in humans is needed. It may start off with only a few patients, in order to ensure safety, while in later phases of clinical trials, researchers learn more about the new approach’s risks and benefits.

Why do they need volunteers?

Volunteers can play an important role at this stage of development, which is crucial for new treatments to reach pharmacy shelves. Without sufficient numbers of trial participants, the drug development process stalls and a trial must be repeated, scaled back or, even worse, the potential new therapy is abandoned. This lengthens the time it takes for new treatments to come to market. No amount of funding or other resources can compensate for the lack of clinical research volunteers.

According to the Foundation of Peripheral Neuropathy, across all diseases, 85 per cent across of clinical trials finish late due to difficulties enrolling participants and nearly one-third of trials fail to recruit a single subject and cannot ever begin.

Phases of the trial

Clinical trials are conducted in phases designed to answer a separate research question.

Phase 1 Safety testing of a small batch of healthy volunteers – recruiting only a few patients, usually less than 100. The first few patients to take part (called a cohort or group) are given a very small dose of the drug. If all goes well, the next group have a slightly higher dose. The dose is gradually increased with each group. The researchers monitor the effect of the drug until they find the best dose to give. Doctors/researchers look at how the drug affects the volunteer: How is it absorbed? How is it metabolised and eliminated from the body? Does it cause side effects?
Phase 2 Testing effectiveness and safety on small batch of patients – doctors evaluate the candidate drug’s effectiveness in a larger group of patient volunteers. In this case, researchers compare the efficacy of the drug on the patient compared to a different treatment. Patients are either given a placebo or a drug that is already used for treatment. Some phase 2 trials are randomised. This means the researchers put the people taking part into treatment groups at random. Doctors/ also analyse optimal dose strength and possible side effects.
Phase 3 Testing effectiveness and safety on a much larger group of patient volunteers – Phase 3 trials usually involve many more patients than phase 1 or 2. This is because differences in success rates may be small. So, the trial needs many patients to be able to show the difference. This phase of research is essential in determining whether the drug is safe and effective. Patient volunteers are divided into three groups: the group that gets the standard treatment; the group that gets the new treatment being tested; and if doctors do not know if the new treatment is better than the standard treatment, but they believe it is as good and may be better.
Phase 4 Researching long-term side effects – Phase 4 trials are usually done after a drug has been shown to work and has been granted a licence. The goal of this phase is to continue studying side effects of a new treatment.

If you take part in a clinical trial, you may be one of the first people to benefit from a new treatment.

However, there is also a chance that the new treatment turns out to be no better, or worse, than the standard treatment. It’s a chance / risk, and ultimately it’s your choice if it really is for you.

Where to find clinical trials:

Centerwatch.com – global database of clinical trials
NHS.uk – UK-based clinical trials
UK Clinical Trials Gateway – Educational side of the NHS
Global Register for Inherited Neuropathies – collects clinical and genetic information on patients from around the world diagnosed with various forms of hereditary neuropathies
ClinicalTrials.gov – US health department based clinical trials
World Health Organization – International clinical trials registry platform

HNPP · Medication · Physical Health

Patient-doctor relations and HNPP

Jul 15, 2017Jul 28, 2017 suswatibasu1 Comment

One of the most important parts of your journey with any kind of peripheral neuropathy is to establish good relations with your doctor. Having recently had a bad experience with a locum GP, only reiterates the need for clear communication and real understanding, especially with a condition that seems to relatively unknown.

A strong emotional fit between how a patient ideally seeks to feel and their doctor makes it more likely that the patient follows the doctor’s health advice, according to a study by Stanford psychology Associate Professor Jeanne Tsai and Tamara Sims.

Sims said that by learning how patients want to feel and tailoring treatments accordingly, physicians can enhance their patients’ trust in them. Finding out what matters to a patient in terms of goals and values is important, she noted.

“This may open the lines of communication so that not only do patients listen more, but they open up and disclose more information to their provider,” she said in an interview.

Finding a specialist:

Finding a doctor who has the clinical training to diagnose and treat neuropathy is not an easy task, however. As Russell L. Chin, M.D. Associate Professor of Clinical Neurology at Weill Medical College of Cornell University states, “there is insufficient training even in medical school in the clinical aspects of neuropathy”.

Disclaimer: Everything written is based on personal and other’s testimonies, available journals and research.

Then there is the fact that there is no one test to diagnose neuropathy and 99 per cent of what the doctor must use is subjective and you have a cocktail for a major patient-doctor problem. So what can you do?

Dr Norman Latov, who specialises in neurology at Weill Cornell Medicine in New York, and author of Peripheral Neuropathy: When the Numbness, Weakness and Pain Won’t Stop, states early diagnosis and if possible treatment is critical to preventing severe disability. So where to begin?

First understand that peripheral neuropathy is a neuromuscular disease. You need to find a Board Certified Neuromuscular Neurologist as this increases the odds of finding one who is able to diagnose and treat neuropathy. In this case, I found the name of a hospital and doctor through a similar hereditary neuropathy based organisation (CMT UK) and they were able to give more details.
For those in the US, you may want to visit a neuropathy centre and the NSN website has a list of doctors and centres. It is worth reading LtCol Eugene B Richardson’s experience on finding a doctor, in which he had to try out several before settling on someone more suitable.
Ask a nurse at the local hospital or doctor’s office. Ask a support group leader or even ask another patient in a support group. Everyone has different pieces of the jigsaw in regards to information, so it’s worth searching around for it.
Avoid centres and doctors who claim to cure all neuropathies and offer over-stated claims. This again is mostly for US-based sufferers, as there are more private consultants that offer this kind of treatment.

Once you have found someone suitable, it is important to establish a rapport and relationship in moving forward. According to John A. Senneff in Numb Toes And Other Woes, you need to be as specific as possible in describing your symptoms and health concerns, including when the symptoms started, what they feel like, and lifestyle changes you made when they started, anything in particular that triggers them or anything that relieves your symptoms. [1]

What should you do once you have found a doctor?

In terms of working with your doctor, following are some of the suggestions given:

Educate yourself – Your doctor should not be your only source of information. For example, pharmacists and patient support groups can provide useful information.
Ask questions – If you have not call from a newspaper or magazine you would like to discuss with your doctor, don’t be reluctant to take the material with you to your appointment. If you disagree with what your doctor is prescribing do it in a way not to put him or her on the defensive. You may need to be tactful when asking.
Disclose symptoms and medication – For your initial session remember to mention all of your medications including prescription as well as over the counter. Also be prepared to discuss your symptoms in detail.
Discuss your medical history in depth – Don’t be afraid to divulge information that might be relevant. Your doctor will be much more effective in dealing with your problem if he or she knows as much about the surrounding circumstances as you do.
Be honest – even if it’s uncomfortable with meeting to unhealthy behaviour. It is necessary to tell your doctor the truth.
Take notes – if the explanation is complex have your doctor write it down for you.
Get a second opinion – if your doctor advises an invasive test or therapy that carries risk.[2]

Room for improvement definitely exists in the patient-doctor relationship. As Tsai and Sims note, physicians should recognise that their patients have “effective ideals” that might influence how they respond to physicians. In looking at how doctors can improve, the authors add:

Physicians could evaluate their patients’ ideal affect in light of whether there are more effective health care providers or treatments consistent with those ideals.
If none exist, physicians might discuss with patients how their ideal affect might help or hinder specific health care recommendations and treatments.
More effective interventions aimed at educating clinicians about the importance of ideal affect in health care should be developed.

No matter how difficult it may seem sometimes, there are physicians out there who understands the value of the doctor patient-partnership for patients with hereditary neuropathy.

1. Page 237-238, “Numb Toes And Other Woes”, Senneff, John A., 2001.
2. Page 236, “Numb Toes And Other Woes”, Senneff, John A., 2001.

HNPP · Medication · Physical Health

Can medical marijuana help pain from HNPP?

Jul 13, 2017Mar 6, 2018 suswatibasu3 Comments

cannabis marijuana hnpp hereditary neuropathy

This is a super controversial subject, especially since it’s part of a wider global debate on whether to legalise marijuana for those with chronic illnesses. I say this as some medical professionals I’ve spoken to have recommended it to ease nerve pain from HNPP. It isn’t for everyone for a variety of personal reasons and it is obviously still illegal in most countries.

With marijuana, or cannabis, the advantages include the fact that there has been a long history of use and some evidence of benefits – many patients swear by the herb to relieve their pain, and physicians see it helping those who have few other options. To others, medical marijuana – which lacks both standardised formulations and rigorous clinical testing – represents a challenging deviation from the ideal of evidence-based medicine.

The issue is that one can generalise that medical cannabis has a higher level of testing standards required to meeting the medical standards for dispensing in areas where it has been legalised. These standards do not always apply to recreational use. But this may differ from country to country, from state to state.

This is more of a hypothetical situation for many.

Disclaimer: Everything written is based on personal and other’s testimonies, available journals and research. Please check with your doctor or practitioner before taking new medicines, and do not break your country’s laws.

So is it helpful?

According to Medical Marijuna Inc, a pro-marijuana think-tank, two major cannabinoids found in cannabis, tetrahydrocannabinol (THC) and cannabidiol (CBD), activate the two main cannabinoid receptors (CB1 and CB2) of the endocannabinoid system within the body.

These receptors regulate the release of neurotransmitter and central nervous system immune cells to manage pain levels.

Mark Ware, a pain clinician at McGill University, Montreal, Canada, explained that the CBDs act as modulators, “circuit breakers,” on numerous nervous pathways. Within these pathways, CB receptors are located at many key sensory intersections.

neuropathy

Once the nerve is stimulated by an action potential (normal nerve conduction) endocannabinoids such as anandamide flow retrograde up to the presynaptic terminal to dampen the forward flow of nervous information. This leads to less pain impulses being generated and perceived. This decrease is interpreted as pain relief.

Dr Rosemary Mazanet has done some extensive research on the use of medical marijuana on neuropathic pain. Writing for the Foundation for Peripheral Neuropathy, she said: “Although CBD and THC act differently in the body, they seem to have many of the same medical benefits. Unfortunately, most of this evidence comes from animals, since very few studies on cannabis have been carried out in human patients.”

She adds: “Patients should treat marijuana for medical use like they would any prescription and avoid operating a motor vehicle or heavy machinery, performing child or elder care, and making important decisions while under treatment.”

Unlike opioids, marijuana cannot cause someone to stop breathing, no matter how much they ingest.

What are the side effects?

Increased heart rate
Dry mouth
Reddening of the eyes
Muscle relaxation
Sensation of cold or hot
Anxiety and paranoia are the most commonly reported side effect of smoking marijuana with a high THC content
Alteration of conscious perception
Feelings of well-being, relaxation or stress reduction, increased sensuality, increased awareness of sensation, increased libido, and creativity
With very high doses, THC can induce auditory and visual hallucinations. THC should be used only under the care of a physician by anyone with a mental health history.

Effects of cannabis

Peak levels of cannabis-associated intoxication occur approximately 30 minutes after smoking. The total short-term duration of cannabis effects when smoked is based on the potency, method of smoking (vape) and how much is smoked. Any acute effects that accompany cannabis use usually abate after 6 hours.

When taken orally (in the form of capsules, food or drink), the effects take longer to manifest initially, and generally last longer, typically for 4–10 hours after consumption. Taking marijuana in the form of edibles can have unpredictable effects, since they are delayed and thus harder to predict.

Where is it legal for medicinal use?

Smoking weed is legal to some extent in 30 states in the USA, though the majority only allow consumption for medicinal purposes. So where has medicinal marijuana been legalised?

Countries where medicinal use is legal	Information on how it is used
Argentina	Decriminalised for personal use. Medical cannabis is legal in Chubut since September 2016, and in Santa Fe since November 2016.
Australia	Legal for medicinal and scientific purposes. Decriminalised for personal use in the Northern Territory, South Australia and the Australian Capital Territory.
Bosnia & Herzogovina	In 2016 it was announced that the Ministry of Civil Affairs had formed a task force to explore the legalising of cannabis and cannabinoids for medical purposes.
Canada	Legal with government issued licence for medical or industrial purposes. In April 2016, Health Minister Jane Philpott announced that new legislation would be introduced in spring 2017 to legalise and regulate cannabis in Canada.
Chile	Since 2014, Chile allows the cultivation of cannabis for medical purposes with the authorisation of The Chilean Agriculture Service (SAG). Sale of marijuana-derived medication is allowed on prescription in pharmacies, from December 2015.
Colombia	Legal for up to 22 grams for personal use. No limit for medical or scientific purpose, and if licensed by the “National Anti-narcotics Council”
Croatia	In 2015, the Ministry of Health officially legalised the use of cannabis-based drugs for medical purposes for patients with illnesses such as cancer, multiple sclerosis, or AIDS.
Czech Republic	Medical use of cannabis on prescription has been legal and regulated since 2013
Finland	Since 2006, use of medical cannabis has been possible under a special license. In 2014, 223 licenses were issued.
France	Legislation permitting the sale of medications containing cannabis derivatives was enacted in June 2013.
Germany	On May 4, 2016 the Cabinet of Germany decided to approve the measure for legal cannabis for seriously ill patients who have consulted with a doctor and “have no therapeutic alternative”. German Health Minister, Hermann Gröhe, presented the legal draft on the legalisation of medical cannabis to the cabinet, which took effect in early 2017.
India	Legal or tolerated in several states such as West Bengal, Gujarat, Bihar, Odisha and the North East.
Israel	Illegal for recreational use, but limited medical uses have been permitted since the 1990s
Italy	Licensed cultivation for medical and industrial use is strictly regulated.
Jamaica	On 25 February 2015, the Jamaican House of Representatives passed a law decriminalising possession of up to two ounces of cannabis.
Macedonia	Medical cannabis legalised in 2016.
Mexico	In December 2016, Mexico’s Senate voted to legalise marijuana for medicinal and scientific purposes – this was approved by the Chamber of Deputies in April 2017.
Netherlands	Personal possession has been decriminalised since 1976, and cannabis products are only sold openly in certain local “coffeeshops”
Philippines	Congress introduced House Bill No. 4477 in 2016, known as the Compassionate Use of Medical Cannabis Act, which would legalise the use of medical marijuana.
Poland	Legal for medicinal use only
Portugal	In 2001, Portugal became the first country in the world to decriminalise the use of all drugs
Puerto Rico	In 2015 the Governor of Puerto Rico signed a executive order to legalise cannabis for medicinal use only
Romania	Medical cannabis legalised in 2013.
Slovenia	Cannabis-based drugs are legal for medical use, but not cannabis itself.
Turkey	The cultivation of marijuana is legal in nineteen provinces in Turkey for medicincal and scientific purposes. However, with permission this can also be conducted in other provinces too.
USA	Illegal at the federal level but legal at the state level in Alaska, California, Colorado, Maine, Massachusetts, Nevada, Oregon and Washington, and in Washington, D.C.; decriminalised in eighteen states, medicinal legal in 25 states and Guam. All Indian Reservations are allowed to regulate cannabis laws; laws vary by reservation.
Uruguay	José Mujica has fully legalised any use of Cannabis in Uruguay; law does not specify quantity for “personal amount”

According to the study Medicinal Cannabis and Painful Sensory Neuropathy in the American Medical Association Journal of Ethics, Dr Igor Grant said: “Our society should be able to find ways to separate the medical benefits of making a treatment available to improve lives when indicated from broader social policy on recreational use, marijuana legalization, and unsubstantiated fears that medicinal cannabis will lead to widespread cannabis addiction.”

Nothing is 100 per cent safe, but when you weigh the benefits against the risks, and if you suffer from chronic neuropathic pain, you may find a worthwhile benefit from using medical marijuana, as long as you use it responsibly and you do it legally.

HNPP · Medication · Physical Health

HNPP and Alternative Supplements

Jul 4, 2017Jul 24, 2017 suswatibasu4 Comments

It sounds like there are a lot of good tidbits of information as well as conflicting messages in terms of taking supplements, and other foodstuffs that are said to have wonderful healing properties.

From supporting nerve regrowth to reducing inflammation, there is a whole host of additional organic as well as synthetic tablets and herbs that can be taken with regular medication.

I personally take a selection of Vitamin B tablets and Folic Acid, which was recommended to me by a neurologist, but everyone’s body is different and reacts in different ways.

So is it necessary to take supplements?

Regardless of the cause of your peripheral neuropathy, boosting the health of your nerves through proper diet and supplementation can help slow the spread of your symptoms. However, the sooner you and your doctor can pinpoint a cause, the quicker you can identify and begin the most effective treatment for your symptoms.

While this is by no means a comprehensive list, these medicinal and herbal suggestions have definitely gotten a lot of praise.

Disclaimer: Please check with your doctor or practitioner before taking new medicines. Make sure you’re not allergic.

Magnesium

Magnesium is said to help maintain nerve function, mostly by reducing pain, calming overactive nerves and relaxing your muscles. This calming effect on nerves and muscles helps reduce pain and improve mobility. According to a 2010 study, a major mechanism of pain is the excessive stimulation of a brain chemical called “NMDA.” Magnesium seems to settle down this pain-carrying neurotransmitter without the toxins of other medications.

Low levels magnesium may result in fatigue, cramping and weakness – among other symptoms.

Alternatives to supplements:

So from where else can you get your magnesium intake?

Spinach
Pumpkin seeds
Beans and peas
Fresh fruits
Quinoa

Vitamin B

One common cause of peripheral neuropathy is a deficiency of B vitamins, particularly B12. If a B12 deficiency isn’t treated in a timely fashion, the nerve damage can become permanent. It is the most important link in the chain of the various B vitamins.

However, without vitamin B2 and B6, your body’s ability to properly absorb and make use of these vitamins for the benefit of your nerves becomes significantly handicapped.

Alternatives to supplements:

The NHS website has laid out some of the foods that are high in B12:

Meat
Salmon
Cod
Milk
Cheese
Eggs
Some fortified breakfast cereals

Folic Acid

Folic acid, known as folate in its natural form, helps the body form healthy red blood cells and reduce the risk of central neural tube defects. Folic acid is needed to activate the B12. B6, B9 (folic acid) and B2 are needed for B1 to be absorbed.

If you’re taking folic acid supplements, it’s important not to take too much, as this could be harmful. Folic acid can actually be absorbed by having a healthy diet. Adults need 200mcg of folic acid a day. It can’t be stored in the body, so you need it in your diet every day.

Alternative for supplements:

Folate is found in small amounts in many foods:

Broccoli
Brussel sprouts
Liver (but avoid this during pregnancy)
Spinach
Asparagus
Peas
Chickpeas
Fortified breakfast cereals

Potassium

Potassium helps generate energy so that the nerves can transmit messages. The way it does this is called the sodium-potassium pump. Essentially, there is more potassium inside your cells and more sodium outside. When the gate that allows one or the other to leave or enter the cell opens, potassium leaves and sodium enters. This “pump” generates the energy for your nerves to transmit messages.

Alternatives to supplements:

Sweet potato
White and kidney beans
Dark leafy greens such as spinach
Avocado
Bananas
Certain fish – Wild salmon, tuna, halibut, flounder, and Pacific cod
Milk
Tomato sauces
Dried fruits -Apricots, peaches and figs

Acetyl-L-Carnitine

Acetyl-L-carnitine (ALC) is a naturally occurring amino acid and is potentially effective at preventing peripheral neuropathy as well as lessening neuropathic symptoms once they have developed. ALC has been shown to influence neurotransmitters (NTs), including acetylcholine (organic chemical that works as a neurotransmitter) and dopamine.

Disclaimer: Please check with your doctor or practitioner before taking new medicines. Make sure you’re not allergic and it doesn’t interact with other medications.

Turmeric

Turmeric is an ancient spice commonly used in Ayurvedic and Chinese medicines to treat digestive issues, inflammation, skin conditions, and wounds. Turmeric is also known as an anti-ischemic agent, which helps in regulating blood supply to peripheral nerves. Lack of blood supply to nerves is of the key reason for these nerves not working properly.

Although there is not currently much research to support its standing as an effective anti-inflammatory or that it can benefit nerve issues, there is much anecdotal evidence that it has its advantages.

For more information on how to consume it, visit TheKitchn.com.

Hemp Oil

A slightly more controversial product is Hemp Oil or Cannabidiol (CBD). For many HNPP sufferers, this is harder to come by depending on the laws of your country. However, it is said to benefit users. Two major cannabinoids found in cannabis, activate the two main cannabinoid receptors, which is said to regulate the release of neurotransmitter and central nervous system immune cells to manage pain levels. There are foods and liquids containing hemp that can also be consumed.

Some of the most popular forms of hemp foods include:

Whole hemp seeds
Shelled hemp seed (hemp hearts)
Hemp oil
Hemp protein
Hemp milk

Omega 3 Oils

Research from Queen Mary, University of London suggests that omega-3 fatty acids, which are found in fish oil, have the potential to protect nerves from injury and help them to regenerate.

Omega-3 fatty acids are vital for the body’s normal growth and development because the body cannot manufacture omega-3 fatty acids. Therefore it has to be consumed in foods such as oily fish.

Foods that include Omega 3 include:

Flaxseeds
Fatty / oily fish – wild salmon, halibut, mackerel, tuna
Walnuts

Coq 10

CoQ10 (CoEnzyme Q10) is an antioxidant naturally produced by your body. As it relates to your nerves, CoQ10 plays a role in correction mitochondrial dysfunction, a condition that can lead to a decline in nerve health and cause nerve related problems or pain. Long-term low dose CoQ-10 inhibited neuropathy induced pain, according to a study.

Coq10 can be found in:

Fish- Sardines, Mackerel, salmon, tuna, herring
Beef, Lamb, Pork- organs like heart, liver, kidneys
Eggs
Spinach
Broccoli
Cauliflower
Wheat-germ
Peanuts, Pistachio, sesame seeds
Soyabean oil, Canola oil

Zinc

Don’t go crazy with zinc supplementation because it can cause a secondary copper metabolic problem, however, there are plenty of foods that are naturally high in zinc.

Why do you need zinc for peripheral neuropathy? It turns out that zinc plays a part in modulating the brain and body’s response to stress all along the way. The highest amount of zinc in the body is found in our brains, particularly in a part of our brains called the hippocampus, and it is critical to cell signalling. But you don’t need a huge amount to fulfil your daily quota which can be done quite simply.

Foods that are high in zinc:

Oysters
Crab and lobster
Meat and poultry as well as eggs
Legumes – hummus, chickpeas, lentils, edamame, and black beans
Vegetables – mushrooms, spinach, broccoli, kale, and garlic
Nuts and seeds
Whole grains
Fortified breakfast cereals
Milk and dairy foods
Dark chocolate

If there are any more supplements you would like to add, please feel free to comment below! Do these particular products work for you?

Dark chocolate as a medical aid makes me very happy indeed.

UPDATE: Since writing the initial post, a few other supplements including Coq 10 and Omega 3 Oils has been suggested and added above.