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The symptoms of migraine include eye pain, fatigue, nausea, vomiting, chills, difficulty concentrating and severe pain in the head.
There is an equal amount of boys and girls below the age of twelve who suffer from migraine. As much as painkillers can relief pain, a person suffering from migraine usually needs a combination of medications to relieve the pain caused by multiple activities in the brain.
Pharmaceutical giant, GlaxoSmithKline Consumer Healthcare (GSK) recently introduced Panadol Extra, a new variant of pain relief medication that is 37% stronger than normal Panadol to help relieve strong headaches such as migraine. During the launch at One World Hotel, Professor Dr Chia Yook Chin from University Malaya Medical Center described the different types of headaches, adding that people need to understand that migraines are not a regular headache. During a migraine attack, patients become highly sensitive to lights and sounds and will retreat to a dark and quiet room or corner. Panadol Extra contains caffeine as an additional ingredient to help relieve pain such as migraines, severe toothache and backaches. Panadol Extra is priced at RM 9.90 is available over the counter at leading pharmacies and stores. Amy Goldstein, MD is a Child Neurologist at the Children’s Hospital of Pittsburgh, where she is the Director of Neurogenetics and co-Director of the Neurofibromatosis Clinic. Mitochondrial disease refers to several hundred genetic diseases caused by mutations (or changes) in either mitochondrial DNA or nuclear DNA.
Figure 1, from the Society of Inherited Metabolic Disease (SIMD), shows the five  complexes (Roman numerals I – V). The OXPHOS chain uses our food (broken down by metabolism) and oxygen to make water, carbon dioxide and ATP. Another way to categorize mitochondrial disease is based on what type of defect is occurring due to the genetic mutation. What is the definition of this disorder from the context of how it differs from a healthy state? In some cases, mitochondrial disease is fatal, depending on the clinical symptoms and their severity.
The diagnosis of mitochondrial disease is complicated due to the two genomes (nuclear and mtDNA). There are commercial labs that can do both mtDNA and nuclear gene testing for mitochondrial disease. Prior to genetic testing, the physician or treating clinician must suspect mitochondrial disease. The most common childhood mitochondrial diseases are Leigh syndrome and Alper-Huttenlocher syndrome. In Alper-Huttenlocher syndrome (sometimes called Alpers disease), characteristics include brain atrophy, epilepsy, and neurologic regression. Certain medications can bring out symptoms and cause onset or worsening of mitochondrial disease. Nuclear-encoded mitochondrial genes are mutated in 80% of all disease and tend to present at an earlier age. A child could have many symptoms or disorders due to their mitochondrial disease, or could have only one organ affected. Children with mitochondrial disease may “crash” from a physiologic stressor, such as infection, dehydration, surgery, or anesthesia. A complete blood count (CBC) and comprehensive metabolic panel can check electrolytes, and liver and kidney functions. The previous traditional approach to diagnosis was to test for common mtDNA mutations (MELAS, MERRF, NARP, KSS), to perform a muscle biopsy to measure enzyme activities, and to use enzyme data to guide a gene-by-gene analysis. Although more than 1,000 genes are involved, the actual number of patients with a single disease causing mutation is only a handful at any one testing center or medical center. Besides diagnostic tests, there are other tests that may be necessary to check for organ involvement.
These are checklists of typical symptoms, family history, findings on exam, biochemistry, neuro-imaging and lab testing. Although there is no proven treatment, early treatment of symptoms can improve overall function of the child. It was noted in a recent survey, published by the Mitochondrial Medicine Society (in Reference section of this paper), there is little consensus on this issue.
A rare mitochondrial disease known as MNGIE has been treated with bone marrow transplantation and these clinical trials are ongoing. Another therapy attempted for mitochondrial disorders are hyperbaric oxygen chambers (HBO). Medications should be discussed with a patient’s routine clinician as this must be an individualized decision. Exercise is emerging as a powerful potential therapy for mitochondrial disease, but must be done in a supervised manner by both the clinician as well as a physical therapist.
Clinicians are working together to establish agreement in what symptoms or tests should be followed during a clinical trial with an intervention.
What’s the likelihood that a child will be able to function in an independent capacity as an adult?
The answer to this question depends on which mitochondrial disease the child has and what organs are affected. Children can have both learning disabilities and developmental disabilities due to mitochondrial disease. The Web site also contains further information about Individualized Education Plan (IEP) and other educational information. We have learned that both aerobic activity and resistance training (weight lifting) can be beneficial to patients with mitochondrial disease; however, exercise should be supervised and guided by a physical therapist familiar with mitochondrial disease.
Cystic fibrosis, a life-threatening disorder that severely damages the lungs and digestive system, is marked by an inherited, mutated gene. Amniocentesis is a prenatal test that gathers information about a fetus' health from a sample of amniotic fluid. Heel pain should be treated as soon as it is detected to prevent it from becoming permanent. Ladies should wear high pencil heels only on special occasions and that too for short periods of time.
It relaxes the muscles and relieves heel pain. Pain relieving herbal oil that contains the extract of arnica, ginger, camphor and peppermint are very effective to treating heel pain.
Stop for 10 minutes and as you feel the heel warming up start massaging again for 10 minutes.
Follow a regular exercise regime and proper diet for weight management. You can consult a dietician and a physical trainer for proper guidance to begin your weight management programme.
Since swollen testicles can be caused by so many different things, it is very important to see a doctor for swollen testicles that don't quickly get better on their own. If there is a hard lump in your baby's scrotum that gets larger when he cries, he might have a hernia. Regular headaches are caused by the narrowing of blood vessels and can be cured with aspirin. A headache, on the other hand, is associated with chills and fever besides a throbbing feeling in the head. However, as adults, research shows a higher percentage of women suffering from migraine compared to men. As most painkillers can be purchased over-the-counter, pharmacists must also look out for other signs and symptoms that may require medical attention. This clinically proven combination of active ingredients is safe to be consumed by the elderly and on an empty stomach. She is an Assistant Professor of Pediatrics at the University of Pittsburgh School of Medicine, where she attended medical school.  Dr. These mutations affect the ability for the mitochondria to properly function within a cell. As electrons pass down the chain from complex to complex, protons are pumped across the inner mitochondrial membrane. Like any wasteful factory, the defective ATP factory of the mitochondria can produce “black smoke” known as reactive oxygen species (or oxygen free radicals). Due to the complexity of the genetics involved, sometimes people in the same family (such as two siblings or mother and child) will have the same genetic mutation (genotype) but very different symptoms (phenotype). This is true even for those disorders that in the past have had a poor prognosis, such as Leigh syndrome. The DNA bases are numbered 1-16.569 and 3243 and 8993 refer to the position where these mutations occur. Complications can arise, especially in children who have significant neurologic problems, which can put them at risk for aspiration and respiratory depression. It has improved over past years due to advances in medical knowledge regarding the genes involved, as well as improvements in commercially available genetic testing.
The common saying for mitochondrial disease has been “any symptom, any age, any organ system, and any mode of inheritance”.
Most of these are autosomal recessive, meaning that mom and dad are both carriers of the mutation (usually without symptoms) and that 25% of the children they have may inherit both mutated genes.
An example of a mitochondrial disease that affects only one organ is called LHON, or Leber’s hereditary optic neuropathy, which causes vision loss but rarely other symptoms.
Magnetic resonance imaging (MRI) of the brain is a test commonly ordered for developmental delay, seizures, low muscle tone, or stroke-like episodes.
For example, if a muscle biopsy manifested a decrease in Complex I activity, then Complex I genes would be individually sequenced for mutations.


Additionally, only a handful of genes may have more than 10 patients described with that particular gene causing disease.
It may depend on which mitochondrial disease the child has and the symptoms that could be progressive and therefore must be followed over time. However, there are currently several ongoing clinical trials, with several more in discussion now and soon to open for enrollment.
Some of these have not been tested in a double-blind randomized trial (which is recommended). At this point, there is no other stem cell or bone marrow transplant treatment for mitochondrial disease.
Physical therapy, occupational therapy, speech therapy, vision therapy, and developmental therapy are all indicated for developmental delays, spasticity management, and overall rehabilitation. Patients and families are encouraged to participate in a patient registry so that they can be informed of access to an appropriate clinical trial. One of the medications that needs to be used with extreme caution is valproic acid for epilepsy in the patient who has (as yet to be diagnosed) Alpers syndrome.
Some of the conditions we thought were uniformly progressive and fatal are not (Leigh syndrome, for example). The prognosis is unpredictable without treatment; this is why natural history studies for each condition are so important.
This procedure is referred to as “outcome measures.” Clinicians have learned from numerous studies performed, without proving an effective therapy, which the correct outcome measure needs to be selected for the trial. These include reversible COX (Complex IV) myopathy, TRMU reversible liver failure, and children who outgrow Pearson syndrome (bone marrow and exocrine pancreatic failure). Fatigue and exercise intolerance can contribute to the overall quality of life that a patient experiences. Children might also have poor growth and need a feeding tube placed in order to receive the necessary calories for growth.
Many patients have exercise intolerance and fatigue, which can make exercise particularly challenging, yet therapeutic. Some doctors will prescribe the ketogenic diet in particular for epilepsy, but this needs to be closely monitored in mitochondrial disease patients, as fatty acids are processed in the mitochondria as well, and some people may have a secondary problem with this type of metabolism. If a woman has an mtDNA mutation, she has the possibly of passing any amount of mutated mitochondria to her future children (see Figure 5, courtesy of SIMD NAMA). Mitochondrial Medicine Society Clinical Directors Working Group: Clinical Director’s Work Group.
POLG DNA testing as an emerging standard of care before instituting valproic acid therapy for pediatric seizure disorders. It causes a thick, sticky mucus to build up in the lungs, digestive tract, and other areas of the body and is one of the most common chronic lung diseases in children and young adults. If a woman is at high risk for a genetic disease, a doctor may recommend CVS to determine whether a baby has certain genetic disorders, such as cystic fibrosis, among other diseases. It can be managed with simple home remedies that bear fruitful results if followed regularly. High heels cause unnecessary strain on calves and heels and cause pain. People suffering from heel pain can use heel pads in their shoes to support the heels. Pack some crushed ice in a plastic or cloth bag and gently massage the heel for 10-15 minutes.
You accept that you are following any advice at your own risk and will properly research or consult healthcare professional. This type of hernia happens when soft tissue, usually part of the intestines or the abdominal wall lining, pushes through a weak part of the abdominal wall.
Sexually transmitted diseases such as gonorrhea or chlamydia can cause swelling and pain in the testicles. A doctor will run several tests to determine whether you need treatment at a hospital or clinic, or whether you can treat the problem at home. Speak with your doctor to figure out the cause of the problem, including what treatments you can use to help relieve the swelling. Once you know the cause, it pays to understand the exact treatments available and which one you want to use. Migraine on the other hand is caused by the expansion of blood vessels in the brain and is a disease which is not necessarily associated with tension and stress. People having a migraine prefer to be in a dark and quiet room and require stronger medication than those suffering from a regular headache. People with a family history of migraine are four times more likely to suffer from migraine. A research conducted in 2001 by doctors from the US National Institute of Neurological Disorders and Stroke found that migraine is three times more common in women than men, possibly because migraine is sensitive to hormone fluctuation. If you suffer from migraine, it is best to make an appointment with a doctor to know the best remedy for you and to rule out other possibly life-threatening diseases. Goldstein has had a special interest in neurogenetic and neurometabolic disorders since her Pediatric intern year.
The person affected by mitochondrial disease may experience worsening of symptoms especially during times of metabolic stress (infection, fasting, and surgery) and may not return to their previous level of functioning.
Seizures are a common symptom and pose some risk of a life-threatening event if there is oxygen deprivation or a fall during a seizure. Then, typically from a viral illness, a regression occurs, meaning that the child loses skills they have gained. MRI can detect classic features of mitochondrial disease such as Leigh disease, where a part of the brain called the basal ganglia may show symmetric damage. Spinal fluid can be sent for glucose, protein, cell count, lactate, amino acids, and neurotransmitters. However, the rate of discovery of new mitochondrial genes has grown exponentially and continues to grow every year. Therefore, there are times when urine sediment (for MELAS) or muscle biopsy (for KSS deletions) needs to be performed to find the mtDNA mutation. For example, children with Kearns Sayre syndrome are at risk for cardiac conduction defects. Additionally, many conditions can look like mitochondrial disease, and even cause complex deficiencies in OXPHOS, but due to gene mutations in a gene not primarily involved in the mitochondrial OXPHOS system.
The effectiveness of a particular treatment will vary depending on the gene mutation and severity of symptoms. HBO tends to generate more oxygen free radicals, which is already problematic in mitochondrial disease. Research is being conducted on the amount and length of endurance (aerobic training) and resistance (strengthening) training. If one of the potential therapies is approved by the FDA, clinicians will then need to follow the natural history of the disorder to see how the prognosis changes.
However, children who outgrow Pearson syndrome and the need for transfusions, typically develop symptoms of Kearns-Sayre syndrome within a few years.
Again, each person will have an individual experience based on which disorder, what symptoms, and their severity.
If a metabolic dietician is available, a consultation may provide individual approach to diet, and possibly help some symptoms. Using anin vitro fertilization technique, the nucleus of the egg (with the mother’s DNA) can be placed into a donor egg that has had its nucleus removed. A cystic fibrosis gene test allows a couple to find out if one of both of them are carriers of the cystic fibrosis gene. For walking or jogging you should always wear sports shoes which have shock absorbing qualities.
Injury is one of the most common reasons for a swollen testicle, and given that the area is very sensitive for most men, injury is often recognized immediately. Fortunately, most of the reasons for swollen testicles are temporary and will go away with home remedies. Other possibilities include infections, including things like mumps (which are relatively rare) or a scrotal sac infection (which is more common). In most cases the injury is clear, and could be caused by anything from strenuous exercise to physical trauma. The bulge created by this can be painful and make it look as though your testicles are swollen.
There are usually other symptoms, such as burning upon urination, unusual discharge, and an urge to urinate frequently.
It can also lead to blood in the urine, painful urination, constant urge to urinate and discharge from the penis. That's why it is important to get any persistent swelling checked out by a doctor; but remember, not all cases of swelling mean something as serious as cancer.
It likely won't cause him any pain, but always check with the doctor to make sure everything is okay.
She has been a member of the Board of Trustees of the United Mitochondrial Disease Foundation, and on the medical advisory board for MitoAction. They are unique in that they have their own DNA, called mitochondrial DNA (mtDNA).  One role of the mitochondria includes making energy, or adenosine triphosphate (ATP), for every cell to function. Treatments are aimed at helping the mitochondria produce more ATP or to limit the damage of these free radicals with antioxidants. An example of this is Leigh syndrome pronounced Lee), which is caused by mutations in more than 60 different genes.
It is typical for families to be on a diagnostic odyssey for several years before being diagnosed.


Children develop typical lesions in an area of the brain known as the basal ganglia or brainstem. Other findings that may not be specific to mitochondrial disease include atrophy, white matter disease, and strokes. Genetic studies can be sent for mtDNA (common mutations or full sequencing and deletions), nuclear DNA genes (single gene, grouped as a panel to a specific condition such as all Complex I genes, or all known nuclear genes), or both mtDNA and nuclear DNA genes on a single panel known as dual massive parallel sequencing.
It is impossible to sequence each individual gene, and technology has advanced to what is called “massive parallel sequencing”. This is because the mutation load (or heteroplasmy) may be different from tissue to tissue. At times, the ordering clinician can appeal the medical necessity of a test to the insurance company.
Examples include Rett syndrome, Angelman syndrome, and some of the channelopathies (SCN1A causing epilepsy) that further confuse the picture. In addition, every mitochondrial disease patient should be participating in a patient registry. In some patients, the treatment can be specifically tailored and will be more effective than when treatment is “empiric”.
However, there are many anecdotal reports of a certain supplement helping, so many clinicians will start one or more. Additionally, clinicians are not sure if measuring blood levels is helpful or if there is a certain form or brand of one vitamin that is better than the others. School support via a 504 Education plan or Individualized Education Plan (IEP) would also be helpful; parents may need the help of the school guidance counselor or an education advocate to access necessary school-system supports.
Endurance training helps to prevent deconditioning and improves the number of mitochondria a patient has by stimulating mitochondrial biogenesis. The National Institute of Neurological Disorders and Stroke is currently developing Common Data Elements for Mitochondrial Disease to be used in design of future clinical trials. In this way, a woman can have her own biological children with the exception of her own mtDNA. Though the condition affects all races, it is most common in white people of Northern European descent. If a woman is at high risk for a genetic disease, a doctor may recommend an "amnio" to determine whether a fetus has certain genetic disorders, such as cystic fibrosis, among other diseases. You can use sesame oil for massage as it has the ability to warm up the area and penetrates easily in to the skin.
Sometimes the swelling can be caused by a lump or a cyst within or around the testicle, and that can happen over a period of hours, days or weeks.
Symptoms include pain, swelling, painful intercourse, chills, fever, an unusual discharge and swollen lymph nodes in the body.
It can also be caused by infections of the prostate or epididymis, or some sexually transmitted diseases. She is the current President of the Mitochondrial Medicine Society and a member of the Society for Inherited Metabolic Disorders and the Child Neurology Society, where she helps plan the Neurogenetics Special Interest Group meetings. If there is a mutation in the genes that code for mitochondrial proteins, decreased ATP production leads to energy failure of the cell and, eventually, to the organ.
Symptoms are generally those of energy failure and may affect a single organ or involve three or more organs (multi-systemic). Leigh syndrome can progress quickly or slowly, but many children have low muscle tone, developmental delay, and may have trouble swallowing or breathing on their own. Sometimes mutations are inherited from a parent and sometimes they are de novo, or new, not coming from a parent. When clinicians see strokes that fall outside a blood vessel distribution, mitochondrial disease may be suspected. This means many genes can be sequenced at the same time, greatly improving our efficiency to perform genetic testing via “high-throughput” screening of candidate genes.
Sometimes a skin biopsy can be performed instead of muscle biopsy in order to evaluate the Complex I-IV activities.
The patient registries will serve to help us understand the natural history of some of these disorders. For example, levocarnitine may be more beneficial in a patient with a documented deficiency than someone who has normal levels. Treatment may be beneficial and noted immediately to be helpful or take a few months to notice its effectiveness. They also know that getting vitamins and supplements covered by insurance can be very difficult; some vitamins are relatively expensive.
Resistance training may help improve the number of damaged mitochondria in the muscle for certain disorders. More research needs to be done so that clinicians learn the natural history for these conditions. It helps to stretch the entire muscles of the foot and relieves heel pain. In case of severe pain do the exercise gently and for a lesser period of time. She has received several awards for patient satisfaction, including Best Doctors in Pittsburgh Magazine.
Figure 1 also demonstrates how most of the complexes are made from a combination of mitochondrial encoded and nuclear encoded genes. In mtDNA disorders, symptoms depend on the percentage of mutation and which organs have the mutant mitochondria.
DiMauro and Schon) shows the circular mtDNA and the positions of mutations causing different disease states. An exception is Kearns-Sayre syndrome which is caused by a large deletion of a piece of mtDNA.
Using fresh muscle to frozen muscle has advantages in that additional testing, such as respirometry or oxygen consumption, can be performed.
Another example is folinic acid, or leucovorin, which should be considered for some patients with mitochondrial disease. In some cases, the treatment may not have any noted benefit but could be helpful to stop disease progression.
Patient participation in bioregistries is vitally important, as well as global collaboration so that data can be pooled from every country.
Others might be fine, but then suffer from stroke-like episodes and lose physical ability and sight. Inflammation, torsion of the testes and testicular cancer are also a few reasons why testicles might be swollen. She has contributed to recent literature on the diagnosis, management, and consensus criteria for mitochondrial disease.
For example, patients with the common A3243G mutation can cause MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) at higher mutation loads, and the syndrome known at MIDD (maternally inherited diabetes and deafness) at lower mutation loads.
Therefore, out of the approximately 1,000 genes that code for mitochondrial proteins, more disease genes are yet to be discovered.  When testing looks for mutations specifically in the mtDNA, and known nuclear genes (typically the coding portion only called exons), mutations may be found in up to 60% of patients who fit diagnostic criteria for mitochondrial disease (typical history and symptoms, abnormal biochemistry, abnormal muscle biopsy). There is a patient registry available through the North American Mitochondrial Disease Consortium (NAMDC) with sites throughout the US and Canada, as well as a patient populated registry through the United Mitochondrial Disease Consortium (UMDF). In particular, those with KSS or POLG mutations, which have symptoms from a secondary cerebral folate deficiency, can document with cerebrospinal fluid (CSF) testing if desired prior to supplementation. Individually these conditions may be rare, but collectively the numbers reach an estimate of 1:5,000 people.
She was also involved in the completion of the Common Data Elements for Mitochondrial Disease through the National Institutes of Neurological Disorders and Stroke. MRS can look at the chemical content of different areas of the brain, including elevations in lactate. For a listing of laboratory studies, issues, and muscle testing, please see the Mitochondrial Medicine Society Web page listed at the end. It can be helpful to determine in advance what parameter or symptom could be measured and to tell as few people as possible about the intervention. The Office of Dietary Supplements at the National Institute of Health (NIH) will be holding a special meeting to discuss these issues in December 2014. She has reviewed articles for journals including Pediatric Neurology and Journal of Child Neurology.
The percent heteroplasmy typically needs to reach a certain threshold to manifest specific symptoms.
Elevated lactate can be seen in mitochondrial disease but also in tumors, strokes, and prolonged seizures. An example of measuring effect can be how long a child can walk at the mall or at the zoo before getting tired. Below, in Figure 2, is an example (courtesy of NAMA SIMD), of the symptoms that develop as the mutation load increases for a mitochondrial disease from the T8993G mutation, causing either retinitis pigmentosa, NARP (neuropathy, ataxia, retinitis pigmentosa), or MILS (maternally inherited Leigh syndrome). Getting positive feedback is more valuable than if the same feedback came from someone who knows the child is on a new vitamin. Another issue that can make it difficult to determine is that some patients have “good days” and “bad days,” so trying to follow daily differences could be difficult.
Some doctors may not recommend any vitamins, while others could recommend a list of 10 or more.




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