Charcot–Marie–Tooth disease (CMT) is a neurological disorder affecting the peripheral nerves. Peripheral nerves act as a connection between the central nervous system (CNS), which includes the brain and spinal cord, and the rest of the body.
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The main function of these nerves is to regulate the sensory and motor functions, and hence, an individual diagnosed with CMT has abnormal sensory and motor functions. CMT results due to certain gene alterations and is also named as hereditary motor and sensory neuropathy (HMSN) or peroneal muscular atrophy.
Charcot–Marie–Tooth disease is named after three scientists - Jean-Martin Charcot, Pierre Marie, and Howard Henry Tooth - who identified CMT in 1886. CMT occurs either due to the defect in the nerve axon or due to the damage to the myelin sheath layering the axons, thereby resulting in cessation of the electrical signals transmitted by the nerves.
Charcot–Marie–Tooth disease can be inherited in an autosomal recessive, autosomal dominant, or X-linked dominant fashion.
Charcot–Marie–Tooth disease is categorized into various types according to the type of genetic mutations. Below is a list of various genetic mutations that are responsible for causing various forms of CMT:
Both motor and sensory nerves are affected by Charcot–Marie–Tooth disease, which affects activities like food ingestion, inhalation, walking, and speaking. Early symptoms of CMT usually manifest in early adolescence; however, it may begin in early or during later part of the adult life.
Initially, the longest nerve fibers are affected. Those fibers generally are those of the arms, hands, legs, and feet. Affected individuals may feel limited sensitivity upon touching hot items or may feel weakness in upper and lower limbs. One may even lose sensitivity to touch or may not even feel pain. Some other symptoms are:
CMT is a slowly progressing disease, and the affected person may lead a normal life for many years. However, occasionally, CMT may affect the respiratory muscles, which can become fatal.
Both men and women are affected by Charcot–Marie–Tooth disease. The early symptoms of CMT may start in teens or in early adulthood or during the middle years of life. However, CMT may remain unidentified, wrongly diagnosed, or may get diagnosed at advanced stages; hence, the genuine number of affected people may even be greater than available statistics. Currently, more than 250,000 Americans are affected by CMT.
Physicians usually start the diagnosis of Charcot–Marie–Tooth disease by questioning the medical and family history, which may indicate the extent and type of symptoms.
Furthermore, a physician may conduct certain neurological tests to identify muscle weakness, loss of muscle mass, abnormal tendon reflexes, and loss of sensation in both the upper and lower extremities. Some typical symptoms like high foot arch, hammertoe, flat feet, or upturned feet may direct toward CMT.
One typical sign that is usually present in CMT1 is the elongation of nerves that may, at times, be visible or may be palpable through the skin. These elongated nerves are referred to as hypertrophic nerves, which result due to the thickening of the myelin sheaths. Some other electrodiagnostic tests to confirm CMT are:
Nerve conduction tests: Electrodes are placed over the skin and transmit mild electric shocks for nerve arousal. An abnormal electric impulse may reveal CMT.
Electromyography (EMG): A fine needle electrode is introduced to the muscle via the skin. Electric activity is then determined through relaxing and tightening the muscle.
Biopsy of the nerve: A small portion of a peripheral nerve is removed from the calf muscle and is analyzed in the laboratory to differentiate CMT from other nerve disorders.
Genetic Testing: Genetic tests may be conducted either via blood or saliva. A positive genetic test is a confirmatory marker of CMT; however, a negative test does not rule out the possibility of CMT as some forms of CMT may remain undiagnosed even via genetic testing.
Currently, there is no cure for Charcot–Marie–Tooth disease; however, various therapies like physiotherapy, occupational therapy, orthopedic surgery, and application of orthopedic braces and devices have been found helpful in alleviating disabling symptoms associated with CMT. In some cases, pain killers are also prescribed if the condition turns painful in some patients.
Although it is not possible to regain the atrophied muscles, the best strategy remains to strengthen the unaffected muscles. Alternative therapies, like tailored physiotherapy programs, are also designed to reinforce strength and flexibility.
Physicians recommend moderate exercise; however, overexertion is discouraged to prevent any further damage. Some exercises which are less strenuous and are usually advisable are:
Some other tips which can help in managing Charcot–Marie–Tooth disease are:
Charcot-Marie-Tooth disease (CMT) & Podiatry
About The Study: Counties with higher social vulnerability had lower rates of U.S. Preventive Services Task Force-recommended screening for breast, cervical or colorectal cancer according to the results of this study of 3,141 counties.
Authors: Ryan Suk, Ph.D., M.S., of the University of Texas Health Science Center at Houston School of Public Health, is the corresponding author.
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Scores on the ACT college admissions test by this year's high school graduates hit their lowest point in more than 30 years — the latest evidence of the enormity of learning disruption during the pandemic.
The class of 2022's averagecomposite score was 19.8 out of 36, marking the first time since 1991 that the average score was below 20. What's more, an increasing number of high school students failed to meet any of the subject-area benchmarks set by the ACT — showing a decline in preparedness for college-level coursework.
The test scores, made public in a report Wednesday, show 42% of ACT-tested graduates in the class of 2022 met none of the subject benchmarks in English, reading, science and math, which are indicators of how well students are expected to perform in corresponding college courses.
In comparison, 38% of test takers in 2021 failed to meet any of the benchmarks.
"Academic preparedness is where we are seeing the decline," said Rose Babington, senior director for state partnerships for the ACT. "Every time we see ACT test scores, we are talking about skills and standards, and the prediction of students to be successful and to know the really important information to succeed and persist through their first year of college courses."
ACT scores have declined steadily in accurate years. Still, "the magnitude of the declines this year is particularly alarming," ACT CEO Janet Godwin said in a statement. "We see rapidly growing numbers of seniors leaving high school without meeting college-readiness benchmarks in any of the subjects we measure."
The results offer a lens into systemic inequities in education, in place well before the pandemic shuttered schools and colleges temporarily waived testing requirements. For example, students without access to rigorous high school curriculum suffered more setbacks during pandemic disruptions, Babington said. Those students are from rural areas, come from low-income families and are often students of color.
The number of students taking the ACT has declined 30% since 2018, as graduates increasingly forgo college and some universities no longer require admissions tests. But participation plunged 37% among Black students, with 154,000 taking the test this year.
Standardized tests such as the ACT have faced growing concerns that they're unfair to minority and low-income students, as students with access to expensive test prep or advanced courses often perform better.
Babington defended the test as a measure of college readiness. "Now more than ever, the last few years have shown us the importance of having high-quality data to help inform how we support students," Babington said.
Test scores now are optional for first-year student admission at many institutions. Some colleges, such as the University of California system, even opt for a test-blind policy, where scores are not considered even if submitted.
But many students still take the tests, hoping to get an edge in admissions by submitting their scores. Tyrone Jordan, a freshman at test-optional Arizona State University, said he took the ACT and the SAT to get ahead of other students and help him receive scholarships.
Jordan, who wants to pursue mechanical engineering, said he thinks his rigorous schedule at Tempe Preparatory Academy prepared him for college, and the standardized tests helped support him and his family financially.
"All the test did for me was deliver me extra financial money," Jordan said.
While Jordan was always planning to take the test, many students struggle with access or choose not to take the test since their universities of choice no longer require it. In Alabama, Louisiana, Mississippi, Nevada, Tennessee and Wyoming, everyone is tested.
John Salata says he is grateful his prostate-specific antigen (PSA) was tested when it was, even if it was by accident.
When Salata was 48, his primary care doctor mistakenly checked the box for a PSA test when ordering his panel of bloodwork. When Salata’s score came back high, she referred him to a urologist who gave him an antibiotic.
A few months later, his PSA tested even higher. He had a biopsy and received a diagnosis of cancer. He had a radical prostatectomy (surgery to remove the prostate gland and seminal vesicles after a prostate cancer diagnosis) in January 2011.
“When the pathology came back, it was 60% cancerous and it had spread beyond the surgical margins,” Salata recalls. “If we hadn’t found it, then it probably would have spread outside the prostate within a few years. It would have spread throughout the body. Even at that point in time there are usually no symptoms, so there would’ve been no need for me to see a doctor. Because the guidelines didn’t recommend testing until (age) 55 or 60, it would have gone unnoticed for some time. Then once you’re at stage 4, the care is generally palliative.”
Changes in recommendations for PSA testing as a screen for prostate cancer are a frequent occurrence. Why is it so difficult to decide whether or when it should be done? And what do the changes mean for men over the age of 50 as they enter the risk zone for this cancer type?
PSA is a protein made by prostate cells and released into the bloodstream. It is produced by both cancerous and noncancerous cells, but cancer cells tend to secrete PSA more directly into the blood, so PSA levels are often higher in patients with prostate cancer, according to Dr. Michael S. Leapman, associate professor of urology at Yale School of Medicine and clinical program leader of the Prostate and Urologic Cancers Program at Yale Cancer Center in New Haven, Connecticut.
“The PSA test does not diagnose prostate cancer,” Leapman says. “If you have a higher than average PSA, you’re identified to be in a higher risk category that typically triggers further investigation.”
PSA is specific to the prostate but not to prostate cancer, notes Dr. Mihir M. Desai, professor of clinical urology and director of robotic urologic surgery at Keck Medicine of USC in Los Angeles. High PSA levels also can be caused by infections, inflammation and other prostate procedures.
As with many cancer types, some prostate cancers may be so slow growing that they will not affect a patient significantly in their lifetime, so their detection and treatment may end up being worse than the cancer having been left alone. To ensure that prostate cancer screening is focused on those who would benefit, there are multiple organizations that issue medical guidelines in the United States, including the American Urological Association, National Comprehensive Cancer Network and American Cancer Society. Each formulates its guidelines based on data from clinical trials that are available at that time.
A patient may find that their PSA test is ordered by a primary care doctor who consults one source, and then by a urologist who consults another.
The U.S. Preventive Screening Task Force (USPSTF), an organization made up of public health and primary care experts, changed its PSA recommendations in 2018. According to their website, that year, the recommendation for men 55 to 69 years old to undergo periodic PSA-based screening for prostate cancer should be an individual one, and that clinicians should not screen men who do not express the preference.
Additionally, the recommendations were against PSA-based screening in men 70 years and older.
“In 2012, the USPSTF issued a statement saying that no one should be screened for prostate cancer with the PSA test. At the time, the judgment from the USPSTF was that the net harms of screening outweighed the potential benefit,” Leapman says.
This recommendation was based on the Prostate, Lung, Colorectal and Ovarian Cancer Screening (PLCO) trial. In the trial, investigators randomly assigned men into two groups: those who were given a PSA test and those who were not. The trial results, released in 2009, showed that the difference in number of deaths between the two groups was statistically insignificant.
Also in 2009, results of the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial were published. The trial was similar to the PLCO trial in that participants were randomly assigned into groups to receive PSA screening or not. However, results of the ERSPC showed a 29% relative reduction in mortality for the PSA-tested group.
Why the difference?
“One question we asked was how was the U.S. study conducted?” Leapman adds. “The main concern was that there was significant contamination — about 90% of the people in the ‘do not screen’ group had actually received PSA testing at some point. It really minimized the potential benefit that could have been seen because men were getting diagnosed in both groups. That contamination was not as prevalent in the European study.”
“The test itself is just a blood test,” Leapman says. “It’s usually combined with other routine bloodwork. So it’s not the test itself that is dangerous; it’s really what happens downstream.”
Often, the next step after receiving a high PSA test score is a biopsy. Dr. Kenneth Lin, professor of clinical family medicine at MedStar Georgetown University Hospital in Washington, D.C., says there can be real harm in this.
“Many men can be told they don’t need a definitive intervention,” Lin explains. “But nonetheless, when someone is walking around thinking there is some probability they have cancer, it often pushes them into treatments they don’t need because they’re never absolutely certain they don’t have it. So a lot of men do have removal of the prostate or radiation therapy when they don’t need to.”
Henry Wigglesworth, 64, is one such patient. When he was 55, he started having his PSA level tested regularly, and it climbed slowly and steadily in the following years until it reached 5. A score between 4 and 10 is in the range of “suspicious,” and approximately 25% of these patients with a score in that range have prostate cancer. Wigglesworth received a diagnosis of a nonaggressive form of prostate cancer in 2017.
“I still remember getting the call,” Wigglesworth says. “My urologist said the results of my biopsy showed I had cancer. Nobody wants to hear that. Then he said the good news was that I had the least harmful type of cancer that exists. It was still very upsetting. I’m healthy in all other respects. I never thought I would have cancer.”
That doctor recommended active surveillance that included frequent monitoring, but then told Wigglesworth that most men usually ended up opting for some form of treatment after five years or so. This prompted Wigglesworth to enroll in a study through the National Institutes of Health (NIH), where they monitored his cancer with regular PSA tests, MRIs and biopsies. They didn’t find any signs of progression.
When Wigglesworth later went to a urologist about his enlarged prostate, he explained his history, and the urologist said he never would have ordered the biopsy because Wigglesworth’s inflamed prostate likely had caused the high PSA result.
Approximately a year after the first biopsy, Wigglesworth returned to NIH. His doctor found a lesion, and Wigglesworth had another biopsy. He left the NIH with a catheter that remained in for four days. When the results came back inconclusive, the doctor ordered another biopsy.
“And I said, ‘No,’” Wigglesworth recalls. “I’m sorry. I’m not going to let you poke me again with that needle.”
While Wigglesworth has opted for active surveillance for his prostate cancer, Salata’s story shows the dangers of not testing. His cancer could have been diagnosed later in life, at the recommended age for testing, when, as he said, it could have been too late.
After the results of the ERSPC trial in 2018, the USPSTF updated its recommendations to state doctors should discuss the benefits and risks of PSA screening with patients who are between the ages of 55 and 69.
“PSA testing shouldn’t be a knee-jerk reaction,” Desai explains. “If patients are warned upfront that ‘Look, even if we do detect prostate cancer, it may be low risk and low grade, and we don’t even need to treat it,’ then they’re much more accepting of that fact afterward, so you can minimize the risk of overtreatment.”
Leapman says the use of active surveillance (close monitoring) as a form of treatment increased in the years USPSTF did not recommend PSA screening. This means prostate cancer is less likely to be overtreated. Desai uses a number of tools to assess a patient’s prostate cancer risk, including looking at the trajectory of their PSA numbers.
“If somebody has a brisk upshoot that doesn’t go down, then that’s more concerning,” Desai says. “If it happens in somebody who has a strong family history, that is concerning. African American men have a higher risk of prostate cancer, so the trigger for a biopsy is lower.”
The general trigger, or signal, to do a biopsy is when the PSA is at 4 or higher. However, if there is a quick upshoot, if the patient is Black or if there is a family history of prostate cancer, physicians may decide to do a biopsy with a lower PSA level.
But even with discussion, there are still overlooked costs of running PSA tests.
“I’d rather spend five minutes counseling somebody about nutrition or exercise,” Lin says. “But I may not have that time because I’m committed to discussing this test, which I think has a pretty marginal benefit at best.”
Leapman says the number of men given PSA tests decreased by approximately 15% between 2012 and 2018.
“After 2018 when the guidelines were changed,” he says, “there was a significant increase. We estimate that rates of testing have approximately gone back to levels prior to 2012.”
There were fewer PSA tests given during those years, but was there a decrease in the number of prostate cancer cases diagnosed?
“Overall the total incidence of prostate cancer has gone down because less testing means fewer biopsies, which means less detection,” Desai says. “But there is also evidence that the incidence of advanced or metastatic disease has begun to go up.”
Lin says the studies for these years can be challenging to interpret.
“What I’ve seen is that the percentage of cancers being diagnosed at a more advanced stage has gone up relative to the lower, earlier-stage cancers,” Lin says. “But you would expect that to happen because we were no longer screening as much. The proportions have changed. I haven’t seen good data showing that the absolute number of late-stage cancers has gone up relative to the population.”
Although MRIs have been around for a while, Leapman says the quality of the image has improved and can reliably show cancer in the prostate. This makes the biopsy more targeted and accurate.
“I think the MRI will hopefully spare some men biopsies,” Lin says. “Or if they have to undergo a biopsy, it’ll be more definitive.”
There are also other blood and urine-based biomarkers that when taken together with a PSA, Leapman says, can help doctors calculate the patient’s prostate cancer risk.
Salata and Wigglesworth say they have moved on with their lives. Salata says he was the first in his family to receive a diagnosis of prostate cancer, but his uncle and cousin also received diagnoses not much later. Salata’s son, who is 26, is planning to have his first PSA test in the next few years.
Wigglesworth notes he recently talked to someone who received a diagnosis of late-stage prostate cancer due to an early PSA test.
“And I thought, Oh my gosh, this test is amazing,” he says. “Everybody should have it. But then there’s the other side, the harm that can be done, not from the test itself, but from this odyssey that you have to go on to identify how it should be treated.”
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A 47-year-old Thai man is in critical condition after two Frenchmen assaulted him in an unprovoked attack caught on camera. According to Lakhana, Somkuan had said, “That car is so beautiful, when will we get a car like this?” They reportedly followed the Porsche to appreciate it for a bit longer before passing. The Porsche then allegedly began tailgating the couple’s motorbike and honked at them until they pulled to the side of the road in front of a grilled pork stall.