84-441: Classifications of Charcot–Marie–Tooth disease refers to the types and subtypes of Charcot–Marie–Tooth disease (CMT), a genetically and clinically heterogeneous group of inherited disorders of the peripheral nervous system characterized by progressive loss of muscle tissue and touch sensation across various parts of the body. CMT is a result of genetic mutations in a number of genes . It has to be kept in mind that sometimes
168-416: A comprehensive metabolic panel screening for diabetes and pre-diabetes, and a serum immunofixation test , which tests for antibodies in the blood. The treatment of peripheral neuropathy varies based on the cause of the condition, and treating the underlying condition can aid in the management of neuropathy. When peripheral neuropathy results from diabetes mellitus or prediabetes , blood sugar management
252-694: A 10–20% response. Three of the seven authors of the review had conflicts of interest declared. In a 2019 Cochrane review of pregabalin the authors conclude that there is some evidence of efficacy in the treatment of pain deriving from post-herpetic neuralgia, diabetic neuropathy, and post-traumatic neuropathic pain only. They also warned that many patients treated will have no benefit. Two of the five authors declared receiving payments from pharmaceutical companies. A 2017 Cochrane systematic review found that oxcarbazepine had little evidence to support its use for treating diabetic neuropathy, radicular pain, and other neuropathies. The authors also call for better studies. In
336-487: A 2015 Cochrane systematic review the authors found a lack of evidence showing any effectiveness of zonisamide for the treatment of pain deriving from any peripheral neuropathy. A 2014 Cochrane review found that studies of levetiracetam showed no indication of its effectiveness at treating pain from any neuropathy. The authors also found that the evidence was possibly biased and that some patients experienced adverse events. A 2013 Cochrane systematic review concluded that there
420-449: A deficient amount of glycyl-tRNA in cells, preventing the elongation phase of protein synthesis . Elongation is a key step in protein production, so when there is a deficiency of glycyl-tRNA, protein synthesis is unable to continue at glycine sites. GARS1 mutations also stall initiation of translation due to a stress response that is induced by glycine addition failure. By stalling elongation and initiation of translation, CMT2D mutations in
504-533: A definitive diagnosis, but not all the genetic markers for CMT are known. CMT is first most noticed when someone develops lower leg weakness, such as foot drop, or foot deformities, including hammertoes and high arches, but signs alone do not lead to diagnosis. Patients must be referred to a physician specialising in neurology or rehabilitation medicine. To see signs of muscle weakness, the neurologist may ask patients to walk on their heels or to move part of their leg against an opposing force. To identify sensory loss,
588-408: A diagnosis of small-fiber peripheral neuropathy. In EMG testing, demyelinating neuropathy characteristically shows a reduction in conduction velocity and prolongation of distal and F-wave latencies, whereas axonal neuropathy shows a reduction in amplitude. Laboratory tests include blood tests for vitamin B 12 levels, a complete blood count , measurement of thyroid stimulating hormone levels,
672-412: A lesion in the central nervous system as a cause, a diagnosis may be made on the basis of symptoms, laboratory and additional testing, clinical history, and a detailed examination. During physical examination , specifically a neurological examination , those with generalized peripheral neuropathies most commonly have distal sensory or motor and sensory loss, although those with a pathology (problem) of
756-436: A particular patient diagnosed with CMT can exhibit a combination of any of the above gene mutations; thus, in these cases precise classification can be arbitrary. Charcot%E2%80%93Marie%E2%80%93Tooth disease Charcot–Marie–Tooth disease ( CMT ) is a hereditary motor and sensory neuropathy of the peripheral nervous system characterized by progressive loss of muscle tissue and touch sensation across various parts of
840-533: A placebo. For tramadol, Cochrane found that there was only modest information about the benefits of its usage for neuropathic pain. Studies were small, had potential risks of bias and apparent benefits increased with risk of bias. Overall the evidence was of low or very low quality and the authors state that it "does not provide a reliable indication of the likely effect". For oxycodone the authors found very low-quality evidence showing its usefulness in treating diabetic neuropathy and postherpetic neuralgia only. One of
924-444: A secondary injury, as prolonged periods of limited mobility can drastically accelerate symptoms of CMT. Pain due to postural changes, skeletal deformations, muscle fatigue, and cramping is fairly common in people with CMT. It can be mitigated or treated by physical therapies, surgeries, and corrective or assistive devices. Analgesic medications may also be needed if other therapies do not provide relief from pain. Neuropathic pain
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#17327730929491008-444: A similarly nonspecific finding that indicates a cycle of denervation / reinnervation . Normally, type I and type II muscle fibers show a checkerboard-like random distribution. However, when reinnervation occurs, the group of fibers associated with one nerve are of the same type. The standard for indicating fiber type is histoenzymatic adenosine triphosphatase (ATPase at pH 9.4). Often, the most important goal for patients with CMT
1092-402: A subtype of muscular dystrophy . Symptoms of CMT usually begin in early childhood or early adulthood but can begin later. Some people do not experience symptoms until their early 30s or 40s. Usually, the initial symptom is foot drop or high arches early in the course of the disease. This can be accompanied by hammertoe , where the toes are always curled. Wasting atrophy of muscle tissue of
1176-410: A sweat test and a tilt table test. Diagnosis of small fiber involvement in peripheral neuropathy may also involve a skin biopsy in which a 3 mm-thick section of skin is removed from the calf by a punch biopsy , and is used to measure the skin intraepidermal nerve fiber density (IENFD), the density of nerves in the outer layer of the skin. Reduced density of the small nerves in the epidermis supports
1260-460: Is a pattern of nerve damage that is quite different from mononeuropathy, often more serious and affecting more areas of the body. The term "peripheral neuropathy" sometimes is used loosely to refer to polyneuropathy. In cases of polyneuropathy, many nerve cells in various parts of the body are affected, without regard to the nerve through which they pass; not all nerve cells are affected in any particular case. In distal axonopathy , one common pattern
1344-414: Is also often the case that the aforementioned medications are prescribed for neuropathic pain conditions for which they had not been explicitly tested on or for which controlled research is severely lacking; or even for which evidence suggests that these medications are not effective. The NHS for example explicitly states that amitriptyline and gabapentin can be used for treating the pain of sciatica. This
1428-672: Is also present in oligodendrocytes , demyelination can appear in the CNS as well. Schwann cells create the myelin sheath by wrapping their plasma membranes around the axon. These Schwann cells work together with neurons and fibroblasts to create a functional nerve. Schwann cells and neurons exchange molecular signals by way of gap junctions that regulate survival and differentiation Demyelinating Schwann cells cause abnormal axon structure and function. They may cause axon degeneration, or they may simply cause axons to malfunction. The myelin sheath allows nerve cells to conduct signals faster. When
1512-494: Is caused by, or associated with, several medical conditions: Autonomic neuropathy is a form of polyneuropathy that affects the non-voluntary, non-sensory nervous system (i.e., the autonomic nervous system ), affecting mostly the internal organs such as the bladder muscles, the cardiovascular system , the digestive tract , and the genital organs. These nerves are not under a person's conscious control and function automatically. Autonomic nerve fibers form large collections in
1596-481: Is completed by the person affected by polyneuropathy. The total score and individual item scores can be followed over time, with item scoring used by the patient and care provider to estimate the clinical status of some of the more common life domains and symptoms impacted by polyneuropathy. The causes are grouped broadly as follows: Peripheral neuropathy may first be considered when an individual reports symptoms of numbness, tingling, and pain in feet. After ruling out
1680-532: Is considered to be targetable for CMT2D treatment. CMT can also be produced by X-linked mutations, in which case it is called X-linked CMT (CMTX). In CMTX, mutated connexons create nonfunctional gap junctions that interrupt molecular exchange and signal transport. The mutation can appear in the GJB1 gene coding for the connexin 32 protein, a gap junction protein expressed in Schwann cells. Because this protein
1764-415: Is despite both the lack of high-quality evidence that demonstrates the efficacy of these medications for that symptom, and also the prominence of generally moderate to high-quality evidence that reveals that antiepileptics in specific, including gabapentin, demonstrate no efficacy in treating it. In general, according to Cochrane's systematic reviews, antidepressants have shown to either be ineffective for
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#17327730929491848-492: Is important to distinguish it from polyneuropathy because when a single nerve is affected, it is more likely to be due to localized trauma or infection. The most common cause of mononeuropathy is physical compression of the nerve, known as compression neuropathy . Carpal tunnel syndrome and axillary nerve palsy are examples. Direct injury to a nerve, interruption of its blood supply resulting in ( ischemia ), or inflammation also may cause mononeuropathy. " Polyneuropathy "
1932-608: Is integral to protein translation and attaches glycine to its cognate tRNA. Many different mutations have been found in CMT2D patients, and it remains unclear how mutations in GARS1 cause CMT2D. However, it is thought that mutant glycyl-tRNA synthetase (GlyRS) interferes with transmembrane receptors, causing motor disease, and that mutations in the gene could disrupt the ability of GlyRS to interact with its cognate RNA, disrupting protein production. The GARS1 mutations present in CMT2D cause
2016-426: Is key to treatment. In prediabetes in particular, strict blood sugar control can significantly alter the course of neuropathy. In peripheral neuropathy that stems from immune-mediated diseases, the underlying condition is treated with intravenous immunoglobulin or steroids. When peripheral neuropathy results from vitamin deficiencies or other disorders, those are treated as well. A range of medications that act on
2100-1228: Is named after those who classically described it: the Frenchman Jean-Martin Charcot (1825–1893), his pupil Pierre Marie (1853–1940), and the Briton Howard Henry Tooth (1856–1925). Ankyrin : Long QT syndrome 4 Peripheral neuropathies Peripheral neuropathy , often shortened to neuropathy , refers to damage or disease affecting the nerves . Damage to nerves may impair sensation, movement, gland function, and/or organ function depending on which nerve fibers are affected. Neuropathies affecting motor , sensory , or autonomic nerve fibers result in different symptoms. More than one type of fiber may be affected simultaneously. Peripheral neuropathy may be acute (with sudden onset, rapid progress) or chronic (symptoms begin subtly and progress slowly), and may be reversible or permanent. Common causes include systemic diseases (such as diabetes or leprosy ), hyperglycemia-induced glycation , vitamin deficiency , medication (e.g., chemotherapy , or commonly prescribed antibiotics including metronidazole and
2184-554: Is often a symptom of CMT, though, like other symptoms of CMT, its presence and severity vary from case to case. For some people, pain can be significant to severe and interfere with daily life activities. However, pain is not experienced by all people with CMT. When neuropathic pain is present as a symptom of CMT, it is comparable to that seen in other peripheral neuropathies , as well as postherpetic neuralgia and complex regional pain syndrome , among other diseases. Atypical presentations of CMT can also lead to leg muscles, specifically
2268-667: Is revealed in many of the Cochrane systematic reviews listed below, studies of these medications for the treatment of neuropathic pain are often methodologically flawed and the evidence is potentially subject to major bias. In general, the evidence does not support the usage of antiepileptic and antidepressant medications for the treatment of neuropathic pain. Better-designed clinical trials and further review from non-biased third parties are necessary to gauge just how useful for patients these medications truly are. Reviews of these systematic reviews are also necessary to assess their failings. It
2352-466: Is simultaneous or sequential involvement of individual noncontiguous nerve trunks , either partially or completely, evolving over days to years and typically presenting with acute or subacute loss of sensory and motor function of individual nerves . The pattern of involvement is asymmetric. However, as the disease progresses, deficit(s) becomes more confluent and symmetrical, making it difficult to differentiate from polyneuropathy. Therefore, attention to
2436-419: Is tested with a 128-Hz tuning fork , and decreased sensation of light touch when touched by a nylon monofilament. Diagnostic tests include electromyography (EMG) and nerve conduction studies (NCSs), which assess large myelinated nerve fibers. Testing for small-fiber peripheral neuropathies often relates to the autonomic nervous system function of small thinly- and unmyelinated fibers. These tests include
2520-408: Is that the cell bodies of neurons remain intact, but the axons are affected in proportion to their length; the longest axons are the most affected. Diabetic neuropathy is the most common cause of this pattern. In demyelinating polyneuropathies, the myelin sheath around axons is damaged, which affects the ability of the axons to conduct electrical impulses. The third and least common pattern affects
2604-425: Is thought to be caused by aberrant gain-of-function missense mutations . The GARS1 gene is a protein-coding gene responsible for the encoding of glycyl-tRNA synthetase (GlyRS). Glycyl-tRNA synthetase is a class II aminoacyl-tRNA synthetase and acts as the catalyst for the synthesis of glycyl-tRNA by covalently bonding amino acids with their corresponding cognate tRNAs for protein translation . Glycyl-tRNA synthetase
Charcot–Marie–Tooth disease classifications - Misplaced Pages Continue
2688-407: Is to maintain movement, muscle strength, and flexibility. Therefore, an interprofessional team approach with occupational therapy (OT), physical therapy (PT), orthotist, podiatrist, and or orthopedic surgeon is recommended. Appropriate footwear is also very important for people with CMT, but they often have difficulty finding well-fitting shoes because of their high-arched feet and hammertoes. Due to
2772-662: The cell bodies of neurons directly. This affects the sensory neurons (known as sensory neuronopathy or dorsal root ganglionopathy ). The effect of this is to cause symptoms in more than one part of the body, often symmetrically on the left and right sides. As for any neuropathy, the chief symptoms include motor symptoms such as weakness or clumsiness of movement; and sensory symptoms such as unusual or unpleasant sensations such as tingling or burning ; reduced ability to feel sensations such as texture or temperature, and impaired balance when standing or walking. In many polyneuropathies, these symptoms occur first and most severely in
2856-399: The fluoroquinolone class of antibiotics (such as ciprofloxacin , levofloxacin , moxifloxacin )), traumatic injury , ischemia , radiation therapy , excessive alcohol consumption, immune system disease , celiac disease , non-celiac gluten sensitivity , or viral infection. It can also be genetic (present from birth) or idiopathic (no known cause). In conventional medical usage ,
2940-484: The neuromuscular junction (NMJ). The neuromuscular junction is abnormal in CMT2D mice, with subjects showing neuromuscular junction degeneration in hind muscles. The dorsal root ganglia (DRG) are also affected via aberrant sensory neuron fate, meaning that sensory neuron cell fates are abnormally determined. CMT2D mice have fewer proprioceptive and mechanosensitive neurons, but have more nociceptive neurons, possibly due to mutant GlyRS aberrantly interacting with
3024-401: The peripheral nervous system . Symptoms depend on the nerves involved, but may include pain , paresthesia (pins-and-needles), paresis (weakness), hypoesthesia (numbness), anesthesia , paralysis , wasting, and disappearance of the reflexes . Causes of neuritis include: Types of neuritis include: Those with diseases or dysfunctions of their nerves may present with problems in any of
3108-435: The soleus muscle , forms the triceps surae muscles (distal calf muscles), occurs causing the known "stork leg deformity". In most cases, ankle-foot orthoses that have functional elements for the foot lifting and adjustable control of the lowering of the forefoot make sense. Weak calf muscles lead to insufficient activation of the forefoot lever. This leads to an additional increasing uncertainty when standing and walking. If
3192-587: The GARS1 gene cause translational repression, meaning that overall translation is inhibited. GARS1-associated axonal neuropathy is progressive , meaning that it worsens over time. Unknown mechanisms are thought to cause the chronic neurodegeneration resulting from the aberrant GlyRS; however, one theory on the mechanism for the disease is VEGF deficiency. Mutant GlysRS interferes with neuronal transmembrane receptors, including neuropilin 1 (Nrp1) and vascular endothelial growth factor (VEGF) , causing neuropathy. GARS-CMT2D mutations alter GlyRS and allow it to bind to
3276-509: The Nrp1 receptor, interfering with the normal binding of Nrp1 to VEGF. While enhanced expression of VEGF improves motor function, reduced expression of Nrp1 worsens CMT2D; because Nrp1 binds to mutant GlyRS in mutant GARS1-CMT2D individuals, Nrp1 expression is reduced, in turn worsening motor function. Mice with deficient VEGF demonstrate motor neuron disease over time. Thus, the VEGF/Nrp1 pathway
3360-402: The affected glands and organs, but common symptoms are poor bladder control, abnormal blood pressure or heart rate, and reduced ability to sweat normally. Peripheral neuropathy may be classified according to the number and distribution of nerves affected (mononeuropathy, mononeuritis multiplex, or polyneuropathy), the type of nerve fiber predominantly affected (motor, sensory, autonomic), or
3444-412: The autonomic nervous system, but not the only one; some conditions affecting the brain or spinal cord also may cause autonomic dysfunction , such as multiple system atrophy , and therefore, may cause similar symptoms to autonomic neuropathy. The signs and symptoms of autonomic neuropathy include the following: Neuritis is a general term for inflammation of a nerve or the general inflammation of
Charcot–Marie–Tooth disease classifications - Misplaced Pages Continue
3528-407: The axon towards the synapses . This prevents the synapses from functioning. CMT is a heterogeneous disease and the mutations linked to it may occur in many different genes. Based on the affected gene, CMT is categorized into several types and subtypes. CMT2 variants are typically referred to as axonal neuropathies due to the axonal degeneration observed. CMT2 variants are a result of damage to
3612-456: The benefit of antidepressant medications for several types of chronic non-cancer pains (including neuropathic pain) in children and adolescents and the authors found the evidence inconclusive. A 2017 Cochrane systematic review found that daily dosages between 1800–3600 mg of gabapentin could provide good pain relief for pain associated with diabetic neuropathy only. This relief occurred for roughly 30–40% of treated patients, while placebo had
3696-763: The body are affected it is called " mononeuritis multiplex ", "multifocal mononeuropathy", or "multiple mononeuropathy". Neuropathy may cause painful cramps , fasciculations (fine muscle twitching), muscle loss, bone degeneration, and changes in the skin, hair, and nails. Additionally, motor neuropathy may cause impaired balance and coordination or, most commonly, muscle weakness; sensory neuropathy may cause numbness to touch and vibration, reduced position sense causing poorer coordination and balance, reduced sensitivity to temperature change and pain, spontaneous tingling or burning pain, or allodynia (pain from normally nonpainful stimuli, such as light touch); and autonomic neuropathy may produce diverse symptoms, depending on
3780-407: The body. This disease is the most commonly inherited neurological disorder , affecting about one in 2,500 people. It is named after those who classically described it: the Frenchman Jean-Martin Charcot (1825–1893), his pupil Pierre Marie (1853–1940), and the Briton Howard Henry Tooth (1856–1925). There is no known cure. Care focuses on maintaining function. CMT was previously classified as
3864-478: The calf muscles are weak, an orthosis should therefore be equipped with functional elements to activate the forefoot lever. An orthotic joint with an adjustable dynamic dorsiflexion stop with a strong spring in combination with a lower leg shell in front of the shin is recommended for this. Such orthoses help to control foot drop, and instability of the foot and ankle and offer the patient a better sense of balance when standing and walking without restricting mobility and
3948-451: The calves, enlarging. This hypertrophic type of CMT is not caused by the muscles enlarging directly, but by pseudohypertrophy of the legs as fatty tissue enters the leg muscles. Charcot–Marie–Tooth disease is caused by genetic mutations that cause defects in neuronal proteins. Nerve signals are conducted by an axon with a myelin sheath wrapped around it. Most mutations in CMT affect
4032-775: The central nervous system have been used to symptomatically treat neuropathic pain. Commonly used medications include tricyclic antidepressants (such as nortriptyline , amitriptyline . imapramine , and desipramine , ) serotonin-norepinephrine reuptake inhibitor (SNRI) medications ( duloxetine , venlafaxine , and milnacipran ) and antiepileptic medications ( gabapentin , pregabalin , oxcarbazepine zonisamide levetiracetam , lamotrigine , topiramate , clonazepam , phenytoin , lacosamide , sodium valproate and carbamazepine ). Opioid and opiate medications (such as buprenorphine , morphine , methadone , fentanyl , hydromorphone , tramadol and oxycodone ) are also often used to treat neuropathic pain. As
4116-578: The degradation of sensory axons) are observed along with motor deficits; otherwise, distal hereditary motor neuropathy type V is diagnosed. It is unknown why sensory involvement is so varied between GARS1 neuropathy patients. Symptoms of CMT2D include foot deformity, muscle weakness and cramping, compromised reflexes, loss of sensation, and muscle atrophy, and are similar to the symptoms of both CMT1 and CMT2 variants. Symptoms and severity vary from patient to patient. Mice are often used to model CMT2D, and typically demonstrate aberrant neuromuscular function at
4200-659: The disease can vary. Involuntary grinding of teeth and squinting are prevalent and often go unnoticed by the person affected. Breathing can be affected in some, as can hearing, vision, and neck and shoulder muscles. Scoliosis is common, causing hunching and loss of height. Hip sockets can be malformed. Gastrointestinal problems can be part of CMT, as can difficulty chewing, swallowing, and speaking (due to atrophy of vocal cords ). A tremor can develop as muscles waste. Pregnancy has been known to exacerbate CMT, as well as severe emotional stress. Patients with CMT must avoid periods of prolonged immobility such as when recovering from
4284-416: The disease. Early- and late-onset forms occur with 'on and off' painful spasmodic muscular contractions that can be disabling when the disease activates. Sensory and proprioceptive nerves in the hands and feet are often damaged, while unmyelinated pain nerves are left intact. Overuse of an affected hand or limb can activate symptoms including numbness, spasm, and painful cramping. Symptoms and progression of
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#17327730929494368-483: The disease. The mother and father each had one normal and one mutant copy of this gene and had mild or no symptoms. The offspring who inherited two mutant genes presented fully with the disease. The constant cycle of demyelination and remyelination , which occurs in CMT, can lead to the formation of layers of myelin around some nerves, termed an "onion bulb". These are also seen in chronic inflammatory demyelinating polyneuropathy . Muscles show fiber type grouping,
4452-416: The drug is ineffective for treating neuropathic pain. The authors caution against positive interpretations of the evidence. For sodium valproate the authors of a 2011 Cochrane review found that "three studies no more than hint that sodium valproate may reduce pain in diabetic neuropathy". They discuss how there is a probable overestimate of the effect due to the inherent problems with the data and conclude that
4536-409: The dynamics of the ankle joint. Studies confirm the positive effect of orthoses with adjustable functional elements in patients with paralysis of these muscle groups. It is of great advantage if the resistances of the two functional elements can be set separately from one another in the two directions of movement, dorsiflexion and plantar flexion . The severity of symptoms varies widely even for
4620-500: The evidence does not support its usage. In a 2014 systematic review of carbamazepine the authors believe the drug to be of benefit to some people. No trials were considered greater than level III evidence; none were longer than 4 weeks in length or were deemed as having good reporting quality. A 2017 Cochrane systematic review aiming to assess the benefit of antiepileptic medications for several types of chronic non-cancer pains (including neuropathic pain) in children and adolescents found
4704-647: The evidence inconclusive. Two of the ten authors of this study declared receiving payments from pharmaceutical companies. A Cochrane review of buprenorphine, fentanyl, hydromorphone, and morphine, all dated between 2015 and 2017, and all for the treatment of neuropathic pain, found that there was insufficient evidence to comment on their efficacy. Conflicts of interest were declared by the authors in this review. A 2017 Cochrane review of methadone found very low-quality evidence, three studies of limited quality, of its efficacy and safety. They could not formulate any conclusions about its relative efficacy and safety compared to
4788-403: The extracellular region of tropomyosin receptor kinase, or Trk, receptors. Trk receptors are crucial to the survival and development of sensory neurons; when disrupted, nerve development and survival is disrupted as well, possibly leading to the abnormal sensory neuron counts observed in CMT2D mice. CMT2D is a result of autosomal dominant mutations in the human GARS1 gene located at 7p14.3 and
4872-432: The feet. Autonomic symptoms also may occur, such as dizziness on standing up, erectile dysfunction , and difficulty controlling urination. Polyneuropathies usually are caused by processes that affect the body as a whole. Diabetes and impaired glucose tolerance are the most common causes. Hyperglycemia-induced formation of advanced glycation end products (AGEs) is related to diabetic neuropathy. Other causes relate to
4956-428: The four authors declared receiving payments from pharmaceutical companies. More generally, a large-scale 2013 review found opioids to be more effective for intermediate-term use than short-term use, but couldn't properly assess effectiveness for chronic use because of insufficient data. Most recent guidelines on the pharmacotherapy of neuropathic pain however are in agreement with the results of this review and recommend
5040-527: The genetic cause of a particular patient's disease was precisely determined by sequencing the whole genome of an affected individual. This was done by the scientists employed by the Charcot Marie Tooth Association (CMTA). Two mutations were identified in a gene, SH3TC2 , known to cause CMT. Researchers then compared the affected patient's genome to the genomes of the patient's mother, father, and seven siblings with and without
5124-420: The lack of good sensory reception in the feet, CMT patients may also need to see a podiatrist for assistance in trimming nails or removing calluses that develop on the pads of the feet. Lastly, patients can also decide to have surgery performed by a podiatrist or an orthopedic surgeon. Surgery may help to stabilize the patients' feet or correct progressive problems. These procedures include straightening and pinning
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#17327730929495208-426: The lower parts of the legs may give rise to a "stork leg" or "inverted champagne bottle" appearance. Weakness in the hands and forearms occurs in many people as the disease progresses. High-arched feet ( pes cavus ) or flat-arched feet ( pes planus ) are classically associated with the disorder. Loss of touch sensation in the feet, ankles, and legs as well as in the hands, wrists, and arms occurs with various types of
5292-441: The most common form, length-dependent peripheral neuropathy, pain and parasthesia appear symmetrically and generally at the terminals of the longest nerves, which are in the lower legs and feet. Sensory symptoms generally develop before motor symptoms such as weakness. Length-dependent peripheral neuropathy symptoms make a slow ascent of the lower limbs, while symptoms may never appear in the upper limbs; if they do, it will be around
5376-422: The myelin sheath is damaged, however, nerve signals are slower. This can be measured by a common neurological test, electromyography . When the axon is damaged, the result is a reduced compound muscle action potential . CMT can be diagnosed through three different forms of tests: measurement of the speed of nerve impulses ( nerve conduction studies ), a biopsy of the nerve, and DNA testing. DNA testing can give
5460-449: The myelin sheath, but some affect the axon. Chromosome 17 The most common cause of CMT (70–80% of the cases) is the duplication of a large region on the short arm of chromosome 17 that includes the gene PMP22 . Chromosome 1 Some mutations affect the gene MFN2 , on chromosome 1 , which codes for a mitochondrial protein. Mutated MFN2 causes the mitochondria to form large clusters, or clots, which are unable to travel down
5544-445: The nerve axons , rather than damage to the myelin sheath (as is the case with CMT1). Damaged axons cause slowed transmission of signals to the muscles and brain, causing symptoms including muscle atrophy, weakness, decreased sensitivity, and foot deformity. Symptoms of CMT2 variants typically appear between the ages of 5 and 25. CMT2D is one of 31 CMT2 variants, and is only diagnosed if sensory deficits (such as loss of sensation due to
5628-515: The nerves may be perfectly normal; may show proximal weakness, as in some inflammatory neuropathies, such as Guillain–Barré syndrome ; or may show focal sensory disturbance or weakness, such as in mononeuropathies. Classically, ankle jerk reflex is absent in peripheral neuropathy. A physical examination will involve testing the deep ankle reflex as well as examining the feet for any ulceration . For large fiber neuropathy, an exam will usually show an abnormally decreased sensation to vibration, which
5712-407: The neurologist tests for deep-tendon reflexes, such as the knee jerk, which are reduced or absent in CMT. The doctor may also ask about the patient's family history since CMT is hereditary. The lack of family history does not rule out CMT but is helpful to rule out other causes of neuropathy, such as diabetes or exposure to certain chemicals or drugs. In 2010, CMT was one of the first diseases where
5796-610: The normal nerve functions. Symptoms vary depending on the types of nerve fiber involved. In terms of sensory function, symptoms commonly include loss of function ("negative") symptoms, including numbness , tremor , impairment of balance, and gait abnormality . Gain of function (positive) symptoms include tingling , pain , itching , crawling, and pins-and-needles . Motor symptoms include loss of function ("negative") symptoms of weakness, tiredness , muscle atrophy , and gait abnormalities ; and gain of function ("positive") symptoms of cramps , and muscle twitch ( fasciculations ). In
5880-422: The particular type of polyneuropathy, and there are many different causes of each type, including inflammatory diseases such as Lyme disease , vitamin deficiencies, blood disorders, and toxins (including alcohol and certain prescribed drugs). Most types of polyneuropathy progress fairly slowly, over months or years, but rapidly progressive polyneuropathy also occurs. It is important to recognize that at one time it
5964-479: The pattern of early symptoms is important. Mononeuritis multiplex is sometimes associated with a deep, aching pain that is worse at night and frequently in the lower back, hip, or leg. In people with diabetes mellitus , mononeuritis multiplex typically is encountered as acute, unilateral, and severe thigh pain followed by anterior muscle weakness and loss of knee reflex. Electrodiagnostic medicine studies will show multifocal sensory motor axonal neuropathy. It
6048-446: The physical condition of the affected individuals. If the muscles of the lower extremities are weak, it makes sense to prescribe custom-fabricated orthotics . Depending on which muscle groups are affected, the correct orthoses with appropriate functional elements should be prescribed. A weakness of the tibialis anterior muscle , which lifts the feet, is usually accompanied by an atrophy of the gastrocnemius muscle which, together with
6132-419: The prediabetes group", and stated that "A search for alternate neuropathy causes is needed in patients with prediabetes." The treatment of polyneuropathies is aimed firstly at eliminating or controlling the cause, secondly at maintaining muscle strength and physical function, and thirdly at controlling symptoms such as neuropathic pain . Mononeuritis multiplex , occasionally termed polyneuritis multiplex ,
6216-425: The process affecting the nerves; e.g., inflammation ( neuritis ), compression ( compression neuropathy ), chemotherapy ( chemotherapy-induced peripheral neuropathy ). The affected nerves are found in an EMG (electromyography) / NCS (nerve conduction study) test and the classification is applied upon completion of the exam. Mononeuropathy is a type of neuropathy that only affects a single nerve . Diagnostically, it
6300-405: The same type of CMT. Cases of monozygotic twins with varying levels of disease severity have been reported, showing that identical genotypes are associated with different levels of severity (see penetrance ). Some patients can live a normal life and are almost or entirely asymptomatic. A 2007 review stated that "life expectancy is not known to be altered in the majority of cases." The disease
6384-418: The thorax, abdomen, and pelvis outside the spinal cord . They have connections with the spinal cord and ultimately the brain, however. Most commonly autonomic neuropathy is seen in persons with long-standing diabetes mellitus type 1 and 2. In most—but not all—cases, autonomic neuropathy occurs alongside other forms of neuropathy, such as sensory neuropathy. Autonomic neuropathy is one cause of malfunction of
6468-548: The time that leg symptoms reach the knee. When the nerves of the autonomic nervous system are affected, symptoms may include constipation, dry mouth, difficulty urinating, and dizziness when standing . A user-friendly, disease-specific, quality-of-life scale can be used to monitor how someone is doing living with the burden of chronic, sensorimotor polyneuropathy. This scale, called the Chronic, Acquired Polyneuropathy - Patient-reported Index (CAP-PRI), contains only 15 items and
6552-593: The toes, lowering the arch, and sometimes, fusing the ankle joint to provide stability. CMT patients must take extra care to avoid falling as fractures take longer to heal in someone with an underlying disease process. Additionally, the resulting inactivity may cause the CMT to worsen. The Charcot–Marie–Tooth Association classifies the chemotherapy drug vincristine as a "definite high risk" and states, "vincristine has been proven hazardous and should be avoided by all CMT patients, including those with no symptoms." Several corrective surgical procedures can be done to improve
6636-508: The treatment of neuropathic pain or the evidence available is inconclusive. Evidence also tends to be tainted by bias or issues with the methodology. Cochrane systematically reviewed the evidence for the antidepressants nortriptyline, desipramine, venlafaxine, and milnacipran and in all these cases found scant evidence to support their use for the treatment of neuropathic pain. All reviews were done between 2014 and 2015. A 2015 Cochrane systematic review of amitriptyline found that there
6720-494: The use of opioids. A 2017 Cochrane review examining mainly propoxyphene therapy as a treatment for many non-cancer pain syndromes (including neuropathic pain) concluded, "There was no evidence from randomised controlled trials to support or refute the use of opioids to treat chronic non-cancer pain in children and adolescents." A 2016 Cochrane review of paracetamol for the treatment of neuropathic pain concluded that its benefit alone or in combination with codeine or dihydrocodeine
6804-451: The word neuropathy ( neuro- , "nervous system" and -pathy , "disease of") without modifier usually means peripheral neuropathy . Neuropathy affecting just one nerve is called "mononeuropathy", and neuropathy involving nerves in roughly the same areas on both sides of the body is called "symmetrical polyneuropathy" or simply " polyneuropathy ". When two or more (typically just a few, but sometimes many) separate nerves in disparate areas of
6888-653: Was high-quality evidence to suggest that lamotrigine is not effective for treating neuropathic pain, even at high dosages 200–400 mg. A 2013 Cochrane systematic review of topirimate found that the included data had a strong likelihood of major bias; despite this, it found no effectiveness for the drug in treating the pain associated with diabetic neuropathy. It had not been tested for any other type of neuropathy. Cochrane reviews from 2012 of clonazepam and phenytoin uncovered no evidence of sufficient quality to support their use in chronic neuropathic pain." A 2012 Cochrane systematic review of lacosamide found it very likely that
6972-405: Was no evidence supporting the use of amitriptyline that did not possess inherent bias. The authors believe amitriptyline may have an effect in some patients but that the effect is overestimated. A 2014 Cochrane systematic review of imipramine notes that the evidence suggesting benefit were "methodologically flawed and potentially subject to major bias." A 2017 Cochrane systematic review assessed
7056-647: Was thought that many of the cases of small fiber peripheral neuropathy with typical symptoms of tingling, pain, and loss of sensation in the feet and hands were due to glucose intolerance before a diagnosis of diabetes or pre-diabetes. However, in August 2015, the Mayo Clinic published a scientific study in the Journal of the Neurological Sciences showing "no significant increase in...symptoms...in
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