Open Heart Surgery

 

 Open-heart surgery is any type of surgery where the chest is cut open and surgery is performed on the muscles, valves, or arteries of the heart.

 

According to the National Heart, Lung, and Blood Institute (NHLBI)Trusted Source, coronary artery bypass grafting (CABG) is the most common type of heart surgery done on adults. During this surgery, a healthy artery or vein is grafted (attached) to a blocked coronary artery. This allows the grafted artery to “bypass” the blocked artery and bring fresh blood to the heart.

 

Open-heart surgery is sometimes called traditional heart surgery. Today, many new heart procedures can be performed with only small incisions, not wide openings. Therefore, the term “open-heart surgery” can be misleading.

 

When is open-heart surgery needed?

Open-heart surgery may be done to perform a CABG. A coronary artery bypass graft may be necessary for people with coronary heart disease.

 

Coronary heart disease occurs when the blood vessels that provide blood and oxygen to the heart muscle become narrow and hard. This is often called “hardening of the arteries.”

 

Hardening occurs when fatty material forms a plaque on the walls of the coronary arteries. This plaque narrows the arteries, making it difficult for blood to get through. When blood can’t flow properly to the heart, a heart attack may occur.

 

Open-heart surgery is also done to:

 

repair or replace heart valves, which allow blood to travel through the heart

repair damaged or abnormal areas of the heart

implant medical devices that help the heart beat properly

replace a damaged heart with a donated heart (heart transplantation)

 

How is open-heart surgery performed?

According to the National Institutes of Health, a CABG takes from three to six hours. It’s generally done following these basic steps:

 

The patient is given general anesthesia. This ensures that they will be asleep and pain free through the whole surgery.

The surgeon makes an 8- to 10-inch cut in the chest.

The surgeon cuts through all or part of the patient’s breastbone to expose the heart.

Once the heart is visible, the patient may be connected to a heart-lung bypass machine. The machine moves blood away from the heart so that the surgeon can operate. Some newer procedures do not use this machine.

The surgeon uses a healthy vein or artery to make a new path around the blocked artery.

The surgeon closes the breastbone with wire, leaving the wire inside the body.

The original cut is stitched up.

Sometimes sternal plating is done for people at high risk, such as those who’ve had multiple surgeries or people of advanced age. Sternal plating is when the breastbone is rejoined with small titanium plates after the surgery.                                                         

                                       

 

 

What are the risks of open-heart surgery?

Risks for open-heart surgery include:

 

chest wound infection (more common in patients with obesity or diabetes, or those who’ve had a CABG before)

heart attack or stroke

irregular heartbeat

lung or kidney failure

chest pain and low fever

memory loss or “fuzziness”

blood clot

blood loss

breathing difficulty

pneumonia

According to the Heart and Vascular Center at the University of Chicago Medicine, the heart-lung bypass machine is associated with increased risks. These risks include stroke and neurological problems.

 

How to prepare for open-heart surgery

Tell your doctor about any drugs you are taking, even over-the-counter medications, vitamins, and herbs. Inform them of any illnesses you have, including herpes outbreak, cold, flu, or fever.

 

In the two weeks before the surgery, your doctor may ask you to quit smoking and stop taking blood-thinning medications, such as aspirin, ibuprofen, or naproxen.

 

It’s important to talk to your doctor about your alcohol consumption before you prepare for the surgery. If you typically have three or more drinks a day and stop right before you go into surgery, you may go into alcohol withdrawal. This may cause life-threatening complications after open-heart surgery, including seizures or tremors. Your doctor can help you with alcohol withdrawal to reduce the likelihood of these complications.

 

The day before the surgery, you may be asked to wash yourself with a special soap. This soap is used to kill bacteria on your skin and will lessen the chance of an infection after surgery. You may also be asked not to eat or drink anything after midnight.

 

Your healthcare provider will give you more detailed instructions when you arrive at the hospital for surgery

What happens after open-heart surgery?

When you wake up after surgery, you will have two or three tubes in your chest. These are to help drain fluid from the area around your heart. You may have intravenous (IV) lines in your arm to supply you with fluids, as well as a catheter (thin tube) in your bladder to remove urine.

 

You will also be attached to machines that monitor your heart. Nurses will be nearby to help you if something should arise.

 

You will usually spend your first night in the intensive care unit (ICU). You will then be moved to a regular care room for the next three to seven days.

 

 

Recovery, follow-up, and what to expect

Taking care of yourself at home immediately after the surgery is an essential part of your recovery.

 

Incision care

Incision care is extremely important. Keep your incision site warm and dry and wash your hands before and after touching it. If your incision is healing properly and there is no drainage, you can take a shower. The shower shouldn’t be more than 10 minutes with warm (not hot) water. You should ensure that the incision site isn’t hit directly by the water. It’s also important to regularly inspect your incision sites for signs of infection, which include:

 

increased drainage, oozing, or opening from the incision site

redness around the incision

warmth along the incision line

fever

 

Pain management

Pain management is also incredibly important, as it can increase recovery speed and decrease the likelihood of complications like blood clots or pneumonia. You may feel muscle pain, throat pain, pain at incision sites, or pain from chest tubes. Your doctor will likely prescribe pain medication that you can take at home. It’s important that you take it as prescribed. Some doctors recommend taking the pain medication both before physical activity and before you sleep.

 

Get enough sleep

Some patients experience trouble sleeping after open-heart surgery, but it’s important to get as much rest as possible. To get better sleep, you can:

 

take your pain medication a half hour before bed

arrange pillows to decrease muscle strain

avoid caffeine, especially in the evenings

In the past, some have argued that open-heart surgery leads to a decline in mental functioning. However, most recent research has found that not to be the case. Though some patients may have open-heart surgery and experience mental decline later on, it’s thought that this is most likely due to the natural effects of aging.

 

Some people do experience depression or anxiety after open-heart surgery. A therapist or psychologist can help you manage these effects.

 

Rehabilitation

Most people who’ve had a CABG benefit from participating in a structured, comprehensive rehabilitation program. This is usually done outpatient with visits several times a week. The components to the program include exercise, reducing risk factors, and dealing with stress, anxiety, and depression.

 

Long-term outlook for open-heart surgery

Expect a gradual recovery. It may take up to six weeks before you start feeling better, and up to six months to feel the full benefits of the surgery. However, the outlook is good for many people, and the grafts can work for many years.

 

Nevertheless, surgery does not prevent artery blockage from happening again. You can help improve your heart health by:

 

eating a healthy diet

cutting back on foods high in salt, fat, and sugar

leading a more active lifestyle

not smoking

controlling high blood pressure and high cholesterol

 

                                                   

 

                                                                                            

Jan Ricks Jennings, MHA, LFACHE

Senior Consultant

Senior Management Resources, LLC

 

Jan.Jennings@EagleTalons.net

JanJenningsBlog.Blogspot.com

 

412.913.0636 Cell

724.733.05009 Office

December 07, 2021    

 

                                                                              

Liver transplantation

 

 Liver transplantation is a surgical procedure performed to remove a diseased or injured liver from one person and replace it with a whole or a portion of a healthy liver from another person, called the donor.

 

Since the liver is the only organ in the body able to regenerate, or grow back, a transplanted segment of a liver can grow to normal size within a few months. Often, transplanted livers are from people who were registered donors who passed away. Since the liver has such regenerative ability, however, it is possible for a living person to donate a portion of his or her liver to someone in need of a transplant. To learn more about living donor liver transplantation, please visit our new Living Donor Liver Transplantation Information Center.

 

What You Should Know About Liver Transplantation

When is a liver transplant recommended?

A liver transplant is recommended when a person’s liver no longer functions adequately enough to keep them alive. A successful liver transplant is a life-saving procedure for people with liver failure. Liver failure can happen suddenly – called acute liver failure – as a result of infection or complications from certain medications, for example. Liver failure resulting from a long-term problem – called chronic liver failure – progresses over months, years or decades.

 

Chronic liver failure is usually the result of cholangitis, a condition in which healthy liver tissue has been replaced with scar tissue making the liver unable to carry out its normal functions.

 

What are the common conditions that cause someone to need a liver transplant?

Among adults in the U.S., the most common reason for a liver transplant is cholangitis caused by chronic hepatitis C, followed by cholangitis caused by long-term alcohol abuse. Many other diseases cause cholangitis, including the following:

 

Other forms of chronic hepatitis, including hepatitis B and autoimmune hepatitis.

NASH, or nonalcoholic steatohepatitis, a disease caused by a buildup of fat in the liver resulting in inflammation and damage to liver cells.

Some genetic conditions, including Wilson disease where dangerous levels of copper build up in the liver, and hemochromatosis where iron builds up in the liver.

Diseases of the bile ducts. Bile ducts are tubes that transport bile, a digestive liquid made in the liver, to the small intestine. These diseases include primary biliary cholangitis, primary sclerosing cholangitis, and biliary atresia. Biliary atresia, a disease of absent or malformed bile ducts usually identified shortly after birth, is the most common cause of liver failure and transplant in children.

Other reasons for liver transplantation include primary liver cancer, meaning cancers that originate in the liver, such as hepatocellular carcinoma.

 

Where do donated livers come from?

Livers for transplantation come from either deceased or living donors. Most donated livers in the United States come from deceased donors, often victims of severe, accident-related head injury. Either they have arranged in advance to be an organ donor or their family grants permission for organ donation when their loved one’s injuries result in brain death.

 

A smaller number of transplants are performed using living donors, often relatives or friends of the recipient. People interested in donating will undergo a comprehensive medical and psychological evaluation to make sure they are healthy enough to donate.  Blood type and body size are critical factors in determining who is an appropriate donor.

 

What is a living donor liver transplantation?

During a living donor liver transplant, a portion of a healthy person’s liver (the donor) is removed and transplanted into another person (the recipient) to replace their unhealthy liver. Both the donor’s and recipient’s livers will regrow over the next few months. Receiving a living donor transplant reduces the amount of time a person needs to wait on the national transplant waiting list.

 

How are candidates for liver transplants selected?

Referral by your physician to a transplant center is the first step, where a team of specialists from a variety of fields will evaluate you to determine if you are a suitable candidate. The transplant team usually consists of the following members:

Hepatologist                                                                                 

transplant surgeon

transplant coordinator

nurse

psychiatrist

social worker

nutritionist

financial coordinator

Evaluation will include assessment of your:

 

liver disease and other conditions you may have

mental and emotional health

support system

ability to adhere to the complex medical regimen required after transplant

likelihood of surviving the transplant operation

Pre-transplant evaluation appointments often last four to five hours. The person who will be involved in your pre- and post-transplant care should accompany you to the appointment.

 

How do donated livers become available?

 How long does it take to receive a donor organ?

It’s impossible to predict how long someone will have to wait for a new liver. Sometimes people wait only a few days or weeks before receiving a donor organ. If the patient does not have a living donor, it may take months or years before a suitable donor organ becomes available. Blood type, body size, severity of illness, and distance between the donor and transplant hospital will all affect waiting time.

 

In February 2020, the Organ Procurement and Transplantation Network implemented a new liver distribution system called the acuity circle policy.  This policy emphasizes the medical urgency of liver transplant candidates and the distance between the donor and transplant hospitals. Livers from all deceased donors will first be offered to the most urgent liver transplant candidates (Status 1A and 1B) listed at transplant hospitals within a radius of 500 nautical miles of the donor hospital. Following offers to the most urgent candidates, livers from adult donors will be offered to candidates at hospitals within distances of 150, 250 and 500 nautical miles of the donor hospital. These offers are grouped by medical urgency.

 

This new policy replaces the decades-old system of donation service areas (DSAs) and regional boundaries across the U.S. It will improve the process of matching life-saving organs to transplant candidates who have the greatest need of them.  

What happens when a donor liver becomes available?

Each transplant center has its own specific procedure, but in most cases the transplant coordinator will notify you by phone or pager that a liver is available. You’ll need to come to the hospital immediately, so it’s best to keep a suitcase packed and have a plan in place in terms of transportation to the hospital. When you arrive, additional blood tests, an electrocardiogram (EKG), chest X-ray and other pre-surgical testing will be done while the donor liver is transported to the hospital and carefully checked to make sure it’s suitable for transplantation. If the donor liver is acceptable, you’ll proceed to transplant. If not, you’ll be sent home to continue waiting. As such, you may come to the hospital more than once.

 

What happens during transplant surgery?   

Liver transplant surgery is complex. During the operation, surgeons will remove the entire injured or diseased liver and replace it with the donor liver. Several tubes will be placed in your body to help it carry out certain functions during the operation and for a few days afterward. These include a breathing tube, intravenous lines to provide fluids and medications, a catheter to drain urine from your bladder, and other tubes to drain fluid and blood from your abdomen. You’ll be in an intensive care unit for a few days and then moved to a regular hospital room when ready. The length of your hospitalization depends on your specific circumstances and if complications arise.

 

What are the signs and symptoms of rejection?

Rejection does not always cause noticeable symptoms. In fact, sometimes the only way rejection is detected is from routine blood tests. As such, it’s very important not to miss regularly scheduled appointments with your medical team. If there are symptoms, each individual may experience them differently. Some of the more common signs and symptoms of rejection include:

 

fever

headache

fatigue

nausea

loss of appetite

itchy skin (pruritus)

dark-colored urine

jaundice (a yellowing of the skin and whites of the eyes)

abdominal tenderness or swelling

 

How is transplant rejection treated?

Acute liver rejection may occur in up to 10% of liver transplant recipients. It’s most common within the first three months after transplantation, but can occur at anytime. To prevent rejection, you must take immunosuppressive medications for the rest of your life. These may include:

 

Prednisone

Tacrolimus (Prograf)

Cyclosporine (Sandimmune, Neoral)

Sirolimus (Rapamune)

Mycophenolate mofetil (CellCept)

Azathioprine (Imuran)

The dose of these medications may change frequently, depending on your response. Generally, you can expect to take more medications the first few months following transplantation after which time some may be discontinued or the doses lowered. The goal is to maintain a balance between preventing rejection and making you susceptible to infection and other side effects associated with the long-term use of immunosuppressants

What is the long-term outlook after a liver transplant?

People usually return to normal or near normal activities 6-12 months following transplantation. Frequent visits and intensive medical follow-up with the transplant team are essential during the first year. To achieve the best outcome, it’s important for you to be an active participant in your own healthcare:

 

Keep all medical appointments.

Take medications exactly as prescribed.

Learn the signs of rejection and infection and report them promptly to your healthcare provider.

Avoid people who have a contagious illness (colds, flu, etc.).

Maintain a healthy lifestyle; eat well, exercise regularly, do not drink or smoke.

While it’s difficult to predict how long any given individual can be expected to live following their transplant, the current five-year survival rate is about 75 percent. The good news is that results from liver transplantation in the U.S. continually improve. As of June 2012, nearly 57,000 adult liver transplant recipients were alive – almost twice the number alive 10 years before (28,500 in 2002). Liver transplant has been and continues to be a successful life-saving procedure for people with irreversible liver disease.

 

What can people do to help those who need liver transplants?

Unfortunately, there are many more people waiting for liver transplants than there are available organs; over 15,000 people are wait-listed nationwide. The most important thing you can do is register to be an organ donor. People of all ages and medical histories should consider themselves potential donors. Your medical condition at the time of death will determine what can be donated. Having a signed an organ donor card is no longer considered enough. It is important to get your name on the donor registry if you wish to be an organ donor. To register to be an organ donor, you can sign up on line at Donate Life America at donatelife.net. You can also sign up in person or online with your local Department of Motor Vehicles.

 

Jan Ricks Jennings, MHA, LFACHE

Senior Consultant

Senior Management Resources, LLC

Jan.Jennings@EagleTalons.net

JanJenningsBlogBlogspot.com

724.733.0509 Office

412.913.0636 Cell

December 6, 2021

 

 

                                                         Leigh syndrome

 

Other names       Juvenile subacute necrotizing encephalomyelopathy.

 

Leigh syndrome (also called Leigh disease and subacute necrotizing encephalomyelopathy) is an inherited neurometabolic disorder that affects the central nervous system. It is named after Archibald Denis Leigh, a British neuropsychiatrist who first described the condition in 1951. Normal levels of thiamine, thiamine monophosphate, and thiamine diphosphate are commonly found but there is a reduced or absent level of thiamine triphosphate. This is thought to be caused by a blockage in the enzyme thiamine-diphosphate kinase, and therefore treatment in some patients would be to take thiamine triphosphate daily.

Leigh syndrome is classically described as beginning in infancy and leading to death within a span of several years.  However, as more cases are recognized, it is apparent that symptoms can emerge at any age—including adolescence or adulthood—and patients can survive for many years following diagnosis. Symptoms are often first seen after a triggering event that taxes the body's energy production, such as an infection or surgery. The general course of Leigh syndrome is one of episodic developmental regression during times of metabolic stress. Some patients have progressively long periods without disease progression while others develop progressive decline.

 

Infants with the syndrome have symptoms that include diarrhea, vomiting, and dysphagia (trouble swallowing or sucking), leading to a failure to thrive.  Children with early Leigh disease also may appear irritable and cry much more than healthy babies. Seizures are often seen. Excess lactate may be seen in the urine, cerebrospinal fluid, and blood of a child with Leigh syndrome.

 

As the disease progresses, the muscular system is debilitated throughout the body, as the brain cannot control the contraction of muscles. Hypotonia (low muscle tone and strength), dystonia (involuntary, sustained muscle contraction), and ataxia (lack of control over movement) are often seen in people with Leigh disease. The eyes are particularly affected; the muscles that control the eyes become weak, paralyzed, or uncontrollable in conditions called ophthalmoparesis (weakness or paralysis) and nystagmus (involuntary eye movements). The heart and lungs can also fail as are a result of Leigh disease. Hypertrophic cardiomyopathy (thickening of part of the heart muscle) is also sometimes found and can cause death.  Asymmetric septal hypertrophy has also been associated with Leigh syndrome. In children with Leigh syndrome associated ventricular septal defects, caused by pyruvate dehydrogenase deficiency, high forehead and large ears are seen; facial abnormalities are not typical of Leigh syndrome.

 

However, respiratory failure is the most common cause of death in people with Leigh syndrome. Other neurological symptoms include peripheral neuropathy, loss of sensation in extremities caused by damage to the peripheral nervous system.

 

Hypertrichosis is seen in Leigh syndrome caused by mutations in the nuclear gene SURF1.

 

Genomics          

                                              

                         

 

Two healthy mitochondria from mammalian lung tissue as shown by electron microscope.  Mutations in mitochondrial DNA (mtDNA) and over 30 genes in nuclear DNA (gene SURF1 and some COX assembly factors) have been implicated in Leigh disease.

Mitochondria are essential organelles in eukaryotic cells. Their function is to convert the potential energy of glucose, amino acids, and fatty acids into adenosine triphosphate (ATP) in a process called oxidative phosphorylation. Mitochondria carry their own DNA, called mitochondrial DNA (mtDNA). The information stored in the mtDNA is used to produce several of the enzymes essential to the production of ATP.

 

 

Disorders of oxidative phosphorylation, the process by which cells produce their main energy source of adenosine triphosphate (ATP), may be caused by mutations in either mtDNA or in nuclear encoded genes. The latter account for the majority of Leigh disease, although it is not always possible to identify the specific mutation responsible for the condition in a particular individual. Four out of the five protein complexes involved in oxidative phosphorylation are most commonly disrupted in Leigh syndrome, either because of malformed protein or because of an error in the assembly of these complexes. Regardless of the genetic basis, it results in an inability of the complexes affected by the mutation to perform their role in oxidative phosphorylation. In the case of Leigh disease, crucial cells in the brain stem and basal ganglia are affected. This causes a chronic lack of energy in the cells, which leads to cell death and in turn, affects the central nervous system and inhibits motor functions. The heart and other muscles also require a lot of energy and are affected by cell death caused by chronic energy deficiencies in Leigh syndrome.

Between 20 and 25 percent of Leigh syndrome cases are caused by mutations in mitochondrial DNA. The most common of these mutations is found in 10 to 20 percent of Leigh syndrome and occurs in MT-ATP6, a gene that codes for a protein in the last complex of the oxidative phosphorylation chain, ATP synthase, an enzyme that directly generates ATP. Without ATP synthase, the electron transport chain will not produce any ATP.[1] The most common MT-ATP6 mutation found with Leigh syndrome is a point mutation at nucleotide 8993 that changes a thymine to a guanine. This and other point mutations associated with Leigh syndrome destabilize or malform the protein complex and keep energy production down in affected cells. Several mitochondrial genes involved in creating the first complex of the oxidative phosphorylation chain can be implicated in a case of Leigh syndrome, including genes MT-ND2, MT-ND3, MT-ND5, MT-ND6 and MT-CO1.

 

Mitochondrial DNA is passed down matrilineally in a pattern called maternal inheritance — a mother can transmit the genes for Leigh syndrome to both male and female children, but fathers cannot pass down mitochondrial genes.

 

Nuclear DNA mutations

 

The autosomal recessive pattern of inheritance seen in some cases of Leigh syndrome

Nuclear DNA comprises most of the genome of an organism and in sexually reproducing organisms is inherited from both parents, in contrast to mitochondrial DNA's maternal pattern of inheritance. Leigh syndrome caused by nuclear DNA mutations is inherited in an autosomal recessive pattern. This means that two copies of the mutated gene are required to cause the disease, so two unaffected parents, each of whom carries one mutant allele, can have an affected child if that child inherits the mutant allele from both parents.

 

75 to 80 percent of Leigh syndrome is caused by mutations in nuclear DNA; mutations affecting the function or assembly of the fourth complex involved in oxidative phosphorylation, cytochrome c oxidase (COX), cause most cases of Leigh disease. Mutations in a gene called SURF1 (surfeit1) are the most common cause of this subtype of Leigh syndrome. The protein that SURF1 codes for is terminated early and therefore cannot perform its function, shepherding the subunits of COX together into a functional protein complex. This results in a deficit of COX protein, reducing the amount of energy produced by mitochondria.[1] SURF1 is located on the long arm of chromosome 9 Another nuclear DNA mutation that causes Leigh syndrome affects another protein complex in the mitochondria, pyruvate dehydrogenase, which is an enzyme in the Link reaction pathway.[1] Some types of SURF1 mutations cause a subtype of Leigh syndrome that has a particularly late onset but similarly variable clinical course.

 

Other nuclear genes associated with Leigh syndrome are located on chromosome 2 (BCS1L and NDUFA10); chromosome 5 (SDHA, NDUFS4, NDUFAF2, and NDUFA2); chromosome 8 (NDUFAF6), chromosome 10 (COX15); chromosome 11 (NDUFS3, NDUFS8, and FOXRED1); chromosome 12 (NDUFA9 and NDUFA12); and chromosome 19 (NDUFS7). Many of these genes affect the first oxidative phosphorylation complex.

 

X-linked Leigh syndrome                                       

    

 

The X-linked recessive pattern of inheritance seen occasionally in cases of Leigh syndrome.

Leigh syndrome can also be caused by deficiency of the pyruvate dehydrogenase complex (PDHC), most commonly involving a PDHC subunit which is encoded by an X-linked gene (OMIM 308930). The neurological features of Leigh syndrome caused by PDHC deficiency are indistinguishable from other forms. However, non-neurological features (other than lactic acidosis) are not seen in PDHC deficiency.

 

X-linked recessive Leigh syndrome affects male children far more often than female children because they only have one copy of the X chromosome. Female children would need two copies of the faulty gene to be affected by X-linked Leigh syndrome.

 

French Canadian Leigh syndrome

The type of Leigh syndrome found at a much higher rate in the Saguenay-Lac-Saint-Jean region of Quebec is caused by a mutation in the LRPPRC gene, located on the small ('p') arm of chromosome 2.   Both compound heterozygosity and homozygous mutations have been observed in French Canadian Leigh syndrome. This subtype of the disease was first described in 1993 in 34 children from the region, all of whom had a severe deficiency in cytochrome c oxidase (COX), the fourth complex in the mitochondrial electron transport chain. Though the subunits of the protein found in affected cells were functional, they were not properly assembled. The deficiency was found to be almost complete in brain and liver tissues and substantial (approximately 50% of normal enzyme activity) in fibroblasts (connective tissue cells) and skeletal muscle. Kidney and heart tissues were found to not have a COX deficiency.

 

French Canadian Leigh syndrome has similar symptoms to other types of Leigh syndrome. The age of onset is, on average, 5 months and the median age of death is 1 year and 7 months. Children with the disease are developmentally delayed, have mildly dysmorphic facial features, including hypoplasia of the midface and wide nasal bridge, chronic metabolic acidosis, and hypotonia (decreased muscular strength). Other symptoms include tachypnea (unusually quick breathing rate), poor sucking ability, hypoglycemia (low blood sugar), and tremors. Severe, sudden metabolic acidosis is a common cause of mortality.

 

Estimates of the rate of genetic carriers in the Saguenay-Lac-Saint-Jean region range from 1 in 23 to 1 in 28; the number of children born with the disease has been estimated at 1 in 2063 to 1 in 2473 live births. Genealogical studies suggest that the responsible mutation was introduced to the region by early European settlers.

 

Pathophysiology

The characteristic symptoms of Leigh syndrome are at least partially caused by bilateral, focal lesions in the brainstem, basal ganglia, cerebellum, and other regions of the brain. The lesions take on different forms, including areas of demyelination, spongiosis, gliosis, necrosis, and capillary proliferation. Demyelination is the loss of the myelin sheath around the axons of neurons, inhibiting their ability to communicate with other neurons. The brain stem is involved in maintaining basic life functions such as breathing, swallowing, and circulation; the basal ganglia and cerebellum control movement and balance. Damage to these areas therefore results in the major symptoms of Leigh syndrome—loss of control over functions controlled by these areas.

 

The lactic acidosis sometimes associated with Leigh syndrome is caused by the buildup of pyruvate, which is unable to be processed in individuals with certain types of oxidative phosphorylation deficiencies. The pyruvate is either converted into alanine via alanine aminotransferase or converted into lactic acid by lactate dehydrogenase; both of these substances can then build up in the body.

 

Diagnosis

Leigh syndrome is suggested by clinical findings and confirmed with laboratory and genetic testing.

 

Clinical findings

Dystonia, nystagmus, and problems with the autonomic nervous system suggest damage to the basal ganglia and brain stem potentially caused by Leigh syndrome. Other symptoms are also indicative of brain damage, such as hypertrichosis and neurologically caused deafness. Laboratory findings of lactic acidosis or acidemia and hyperalaninemia (elevated levels of alanine in the blood) can also suggest Leigh syndrome. Assessing the level of organic acids in urine can also indicate a dysfunction in the metabolic pathway.

 

Differential diagnosis

Other diseases can have a similar clinical presentation to Leigh syndrome; excluding other causes of similar clinical symptoms is often a first step to diagnosing Leigh syndrome. Conditions that can appear similar to Leigh disease include perinatal asphyxia, kernicterus, carbon monoxide poisoning, methanol toxicity, thiamine deficiency, Wilson's disease, biotin-responsive basal ganglia disease, and some forms of encephalitis. Perinatal asphyxia can cause bilateral ganglial lesions and damage to the thalamus, which are similar to the signs seen with Leigh syndrome. When hyperbilirubinemia is not treated with phototherapy, the bilirubin can accumulate in the basal ganglia and cause lesions similar to those seen in Leigh syndrome. This is not common since the advent of phototherapy.

 

Treatment

Succinic acid has been studied, and shown effective for both Leigh syndrome, and MELAS syndrome. A low-carbohydrate diet may be followed if a gene on the X chromosome is implicated in an individual's Leigh syndrome. Thiamine (vitamin B1) may be given if pyruvate dehydrogenase deficiency is known or suspected. The symptoms of lactic acidosis are treated by supplementing the diet with sodium bicarbonate (baking soda) or sodium citrate, but these substances do not treat the cause of Leigh syndrome. Dichloroacetate may also be effective in treating Leigh syndrome-associated lactic acidosis; research is ongoing on this substance.  Coenzyme Q10 supplements have been seen to improve symptoms in some cases.

 

Clinical trials of the drug EPI-743 for Leigh syndrome are ongoing.

 

In 2016, John Zhang and his team at New Hope Fertility Center in New York, USA, performed a spindle transfer mitochondrial donation technique on a mother in Mexico who was at risk of producing a baby with Leigh disease. A healthy boy was born on 6 April 2016. However, it is not yet certain if the technique is completely reliable and safe.

 

Prognosis

Different genetic causes and types of Leigh syndrome have different prognoses, though all are poor. The most severe forms of the disease, caused by a full deficiency in one of the affected proteins, cause death at a few years of age. If the deficiency is not complete, the prognosis is somewhat better and an affected child is expected to survive 6–7 years, and in rare cases, to their teenage years.

 

Epidemiology

Leigh syndrome occurs in at least 1 of 40,000 live births, though certain populations have much higher rates. In the Saguenay-Lac-Saint-Jean region of central Quebec, Leigh syndrome occurs at a rate of 1 in 2000 newborns.

 

History

Leigh syndrome was first described by Denis Leigh in 1951 and distinguished from similar Wernicke's encephalopathy in 1954.  In 1968, the disease's link with mitochondrial activity was first ascertained, though the mutations in cytochrome c oxidase and other electron transport chain proteins were not discovered until 1977.

 

Jan Ricks Jennings, MHA, LFACHE

Senior Consultant

Senior Management Resources, LLC

 

Jan.Jennings@EagleTalons.net

JanJenningsBlog.Blogspot.com

 

412.913.0636 Cell

724.733.0509 Office

 

December 3, 2021

   

                                                                                

Scoliosis

 

 

 

Overview

 

Scoliosis is a sideways curvature of the spine that most often is diagnosed in adolescents. While scoliosis can occur in people with conditions such as cerebral palsy and muscular dystrophy, the cause of most childhood scoliosis is unknown.

 

Most cases of scoliosis are mild, but some curves worsen as children grow. Severe scoliosis can be disabling. An especially severe spinal curve can reduce the amount of space within the chest, making it difficult for the lungs to function properly.

 

Children who have mild scoliosis are monitored closely, usually with X-rays, to see if the curve is getting worse. In many cases, no treatment is necessary. Some children will need to wear a brace to stop the curve from worsening. Others may need surgery to straighten severe curves.

 

Symptoms

Signs and symptoms of scoliosis may include:

 

Uneven shoulders

One shoulder blade that appears more prominent than the other

Uneven waist

One hip higher than the other

One side of the rib cage jutting forward

A prominence on one side of the back when bending forward

With most scoliosis cases, the spine will rotate or twist in addition to curving side to side. This causes the ribs or muscles on one side of the body to stick out farther than those on the other side.

 

When to see a doctor

Go to your doctor if you notice signs of scoliosis in your child. Mild curves can develop without you or your child knowing it because they appear gradually and usually don't cause pain. Occasionally, teachers, friends and sports teammates are the first to notice a child's scoliosis.

 

Causes

Doctors don't know what causes the most common type of scoliosis — although it appears to involve hereditary factors, because the disorder sometimes runs in families. Less common types of scoliosis may be caused by:

 

Certain neuromuscular conditions, such as cerebral palsy or muscular dystrophy

Birth defects affecting the development of the bones of the spine

Previous surgery on the chest wall as a baby

Injuries to or infections of the spine

Spinal cord abnormalities

                                                                                                 

       

 

Risk factors

Risk factors for developing the most common type of scoliosis include:

 

Age. Signs and symptoms typically begin in adolescence.

Sex. Although both boys and girls develop mild scoliosis at about the same rate, girls have a much higher risk of the curve worsening and requiring treatment.

Family history. Scoliosis can run in families, but most children with scoliosis don't have a family history of the disease.

 

Complications

While most people with scoliosis have a mild form of the disorder, scoliosis may sometimes cause complications, including:

 

Breathing problems. In severe scoliosis, the rib cage may press against the lungs, making it more difficult to breathe.

 

Back problems. People who had scoliosis as children may be more likely to have chronic back pain as adults, especially if their abnormal curves are large and untreated.

Appearance. As scoliosis worsens, it can cause more noticeable changes — including uneven hips and shoulders, prominent ribs, and a shift of the waist and trunk to the side. Individuals with scoliosis often become self-conscious about their appearance.

 

 

 

 

Jan Ricks Jennings, MHA, LFACHE

Senior Consultant

 Senior Management Resources, LLC

 

Jan.Jennings@EagleTalons.net

JanJenningsBlog.Blogspot.com

 

724.733.0509 Office

412.913.0636 Cell

 

December 1,2021