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Neuropathy

Disease Details

Family Health Simplified

Description
Neuropathy is a condition that occurs when peripheral nerves are damaged, causing weakness, numbness, and pain, often in the hands and feet.
Type
Neuropathy can be classified into various types including:

1. **Peripheral Neuropathy**: This type affects the peripheral nerves.
2. **Autonomic Neuropathy**: This type affects the nerves that control involuntary body functions.
3. **Focal Neuropathy**: This type is characterized by damage to a single nerve.
4. **Proximal Neuropathy**: This type affects nerves in the hips, thighs, or buttocks.

Genetic transmission of neuropathies can vary:

1. **Hereditary Neuropathy**: These include conditions such as Charcot-Marie-Tooth disease (CMT), which is commonly inherited in an autosomal dominant pattern, though autosomal recessive and X-linked patterns are also observed.
2. **Acquired Neuropathy**: These are not typically related to genetic transmission but can result from various external factors like diabetes, infections, or exposure to toxins.

In hereditary cases, the specific pattern of genetic transmission can provide insights into family history and risk factors.
Signs And Symptoms
Those with diseases or dysfunctions of their nerves may present with problems in any of 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 the most common form, length-dependent peripheral neuropathy, pain and parasthesia appears 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 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.
Prognosis
Neuropathy prognosis varies widely depending on the underlying cause, the type of neuropathy, and the timeliness of treatment. Early detection and management can often slow or halt the progression of symptoms. However, in some cases, neuropathy can lead to permanent nerve damage, resulting in chronic pain, loss of sensation, and disability. Proper medical management, lifestyle changes, and, in some instances, physical therapy can improve quality of life for those affected.
Onset
Neuropathy often has a gradual onset, with symptoms developing slowly over time. These symptoms can include numbness, tingling, pain, and muscle weakness. The specific cause, location, and type of nerves affected can influence the onset and progression of the condition.
Prevalence
Neuropathy, particularly peripheral neuropathy, affects approximately 2.4% of the general population. This number can increase to about 8% in individuals aged 55 years and older. The prevalence is higher among people with diabetes, reaching up to 50% in long-term diabetes cases.
Epidemiology
Epidemiology of neuropathy:

Neuropathy, often referred to as peripheral neuropathy, involves damage to the peripheral nerves and can result from various causes, such as diabetes, infections, and autoimmune diseases. The epidemiology varies based on the type and cause:

- **Diabetic Neuropathy**: Among individuals with diabetes, approximately 50% may develop some form of neuropathy.
- **Prevalence**: The overall prevalence of peripheral neuropathy in the general population is estimated to be around 2-3%, rising to 8% in people aged 55 and older.
- **Idiopathic Neuropathy**: In some cases, the cause remains unknown, accounting for 23-36% of neuropathy cases depending on the study.

Neuropathy affects both sexes, though certain types like diabetic neuropathy might show some prevalence differences due to the underlying disease distribution. The prevalence tends to increase with age.

(Note: "nan" is interpreted as potentially a mistaken or incomplete entry and has been excluded from this summary.)
Intractability
Neuropathy can be challenging to treat, and some cases are indeed intractable. The intractability largely depends on the underlying cause, the extent of nerve damage, and how early treatment begins. While some types of neuropathy can be managed effectively with medications, lifestyle changes, and addressing the root cause, others may not respond well to treatment and can lead to persistent symptoms.
Disease Severity
Disease Severity: Neuropathy severity can range from mild to severe, depending on the extent of nerve damage and the underlying cause.

Nan: Nan typically refers to nanometers in different contexts, but in this query, it might be a typo or unclear. If it refers to nutrient availability in neuropathy, patients often need to monitor and manage levels of certain nutrients like B vitamins, which are important for nerve health.
Healthcare Professionals
Disease Ontology ID - DOID:870
Pathophysiology
Neuropathy is a condition involving damage to the peripheral nerves. The pathophysiology of neuropathy typically includes:

1. **Axonal Damage:** Direct injury to the nerve fibers (axons) which may result from trauma, metabolic disturbances (such as diabetes), or toxic exposures.
2. **Demyelination:** Damage to the myelin sheath which insulates nerve fibers, often seen in autoimmune conditions like Guillain-Barré syndrome.
3. **Inflammation:** Inflammatory processes can lead to nerve damage, as seen in various types of vasculitis or infections.
4. **Ischemia:** Reduced blood flow can cause nerve damage due to lack of oxygen and nutrients, often linked to conditions like peripheral artery disease.
5. **Genetic Factors:** Some forms of neuropathy are inherited and result from genetic mutations affecting nerve function and structure.

These mechanisms can result in symptoms such as pain, tingling, numbness, and muscle weakness.
Carrier Status
Carrier status is not applicable to neuropathy. Neuropathy refers to damage or dysfunction of one or more nerves, resulting in symptoms such as pain, numbness, tingling, or weakness, typically in the hands and feet. It can be caused by various factors including diabetes, infections, inherited disorders, toxins, and certain medications, but there is no concept of being a 'carrier' for neuropathy.
Mechanism
Neuropathy refers to a condition that involves damage to the peripheral nerves, which can cause weakness, numbness, and pain, typically in the hands and feet. Here's a brief overview of its mechanisms and molecular mechanisms:

**Mechanism:**
1. **Nerve Damage:** Neuropathy can result from direct injury to nerves, which disrupts their ability to transmit signals properly. This damage can be due to a variety of factors including physical injury, infections, metabolic issues, or toxic exposures.
2. **Impaired Blood Supply:** Poor circulation or blood supply, common in conditions such as diabetes, can deprive nerves of essential nutrients and oxygen, leading to nerve damage.
3. **Autoimmune Reactions:** The body's immune system may mistakenly attack peripheral nerves, as seen in conditions like Guillain-Barré syndrome.

**Molecular Mechanisms:**
1. **Oxidative Stress:** Reactive oxygen species (ROS) and free radicals can damage nerve cells and their supporting structures, contributing to neuropathy. This is particularly relevant in diabetic neuropathy.
2. **Inflammatory Cytokines:** Chronic inflammation can lead to elevated levels of cytokines, such as TNF-α and IL-6, which can damage nerve cells and disrupt signal transmission.
3. **Mitochondrial Dysfunction:** Mitochondria are critical for energy production in cells. Dysfunctional mitochondria can lead to reduced ATP production, energy deficits, and increased oxidative damage.
4. **Deposition of Advanced Glycation End-products (AGEs):** High blood sugar levels can lead to the formation of AGEs, which can accumulate in nerve cells and cause structural and functional damage.
5. **Impaired Ion Channels:** Ion channel dysfunctions, particularly involving sodium, potassium, and calcium channels, can impair nerve signal transmission and lead to symptoms of neuropathy.
6. **Altered Lipid Metabolism:** Abnormalities in lipid metabolism can affect nerve cell membranes and myelin sheaths, leading to compromised nerve function.

Understanding these mechanisms can help in devising targeted treatments for different types of neuropathy.
Treatment
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 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.
Compassionate Use Treatment
For neuropathy, compassionate use treatment, off-label, or experimental treatments can provide additional options for patients when standard therapies are insufficient or unavailable.

1. **Compassionate Use Treatment**: Compassionate use, also known as expanded access, allows patients to gain access to investigational drugs or therapies outside of clinical trials. This is particularly considered for severe neuropathy cases unresponsive to existing treatments. Specific drug access via compassionate use depends on regulatory approval and the individual pharmaceutical company's policies.

2. **Off-label Treatments**: Off-label use involves prescribing approved medications for neuropathy in ways not specifically indicated by the regulatory authority. Common off-label treatments for neuropathy include:
- **Antidepressants**: Medications like amitriptyline or duloxetine may be used to manage neuropathic pain.
- **Anticonvulsants**: Gabapentin and pregabalin, though primarily used for seizures, are often prescribed off-label for neuropathic pain relief.
- **Topical Agents**: Lidocaine or capsaicin patches might be recommended to ease local pain.

3. **Experimental Treatments**: These involve therapies that are still under research but may show promise in treating neuropathy. Experimental treatments include:
- **Stem Cell Therapy**: Investigated for its potential to repair nerve damage.
- **Gene Therapy**: Exploring ways to correct underlying genetic causes of neuropathy.
- **Neuromodulation Devices**: Techniques like spinal cord stimulation or transcutaneous electrical nerve stimulation (TENS) are being studied for neuropathic pain management.
- **Biologics**: Novel biologic agents targeting specific pathways involved in neuropathic pain are under investigation.

All of these approaches require careful consideration and discussion with a healthcare professional to understand their potential benefits and risks.
Lifestyle Recommendations
Lifestyle recommendations for managing neuropathy include:

1. **Healthy Diet**: Eat a balanced diet rich in fruits, vegetables, whole grains, and lean proteins to support overall health.
2. **Regular Exercise**: Engage in low-impact exercises like walking, swimming, or cycling to improve blood flow and reduce symptoms.
3. **Foot Care**: Inspect your feet daily for sores or injuries, and wear comfortable, well-fitting shoes to prevent further damage.
4. **Avoid Alcohol**: Limit or abstain from alcohol, as it can exacerbate nerve damage.
5. **Manage Blood Sugar**: If diabetic, maintain stable blood sugar levels through medication, diet, and regular monitoring.
6. **Stop Smoking**: Quit smoking to improve circulation and overall nerve health.
7. **Stress Management**: Practice relaxation techniques such as yoga, meditation, or deep breathing to reduce stress and pain.
8. **Adequate Sleep**: Ensure you get sufficient rest to help your body heal and manage symptoms.

Consult with a healthcare provider for personalized advice and treatment options.
Medication
A range of medications that act on 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 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 for their failings.
It 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 state that amitriptyline and gabapentin can be used for treating the pain of sciatica. This is despite both the lack of high quality evidence that demonstrates 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.
Repurposable Drugs
For neuropathy, some repurposable drugs that have shown promise include:

1. Gabapentin - Originally used for epilepsy, now commonly prescribed for neuropathic pain.
2. Pregabalin - Similar to gabapentin, also initially for epilepsy, now for neuropathic pain.
3. Amitriptyline - A tricyclic antidepressant that can alleviate nerve pain.
4. Duloxetine - An antidepressant (SNRI) that can treat neuropathic pain.
5. Carbamazepine - An anticonvulsant that stabilizes nerve activity.
6. Lidocaine patches - Originally for local anesthesia, useful in treating localized neuropathic pain.

Please consult a healthcare provider for personalized medical advice.
Metabolites
Neuropathy is a disease affecting the peripheral nerves, often causing weakness, numbness, and pain. Some metabolites associated with neuropathy include:

1. **Methylmalonic Acid**: Elevated levels can indicate vitamin B12 deficiency, often linked to neuropathy.
2. **Homocysteine**: High levels are also associated with vitamin B12 and folate deficiencies, contributing to neuropathy.
3. **Glucose**: Poorly controlled glucose levels can lead to diabetic neuropathy.
4. **2,3-DPG (2,3-Diphosphoglycerate)**: Alterations in its concentration may impact nerve function.

These metabolites can provide insights into underlying causes or the state of neuropathy.
Nutraceuticals
Nutraceuticals such as alpha-lipoic acid, acetyl-L-carnitine, and vitamin B12 have been studied for their potential benefits in managing neuropathy. Alpha-lipoic acid may help reduce oxidative stress and improve nerve function. Acetyl-L-carnitine might aid in nerve regeneration and pain relief, while vitamin B12 is crucial for nerve health and repair. Always consult a healthcare professional before starting any new supplement regimen.
Peptides
Peptides are short chains of amino acids that play essential roles in various biological processes. For neuropathy, certain peptides are being explored for their potential therapeutic benefits. These include:

1. **CGRP (Calcitonin Gene-Related Peptide):** Its role in pain pathway modulation makes it a target for treatment.
2. **PACAP (Pituitary Adenylate Cyclase-Activating Polypeptide):** Involved in neuroprotection and neural repair mechanisms.
3. **Peptide-based growth factors:** Such as NGF (Nerve Growth Factor), which can promote nerve regeneration.

Nanotechnology (nan) is being leveraged to enhance the delivery and efficacy of treatments for neuropathy. Applications include:

1. **Nanoparticles:** Designed to deliver drugs or peptides directly to nerve cells, improving localization and reducing side effects.
2. **Nanofibers:** Used in tissue engineering to create scaffolds that support nerve regeneration.
3. **Liposomes:** Nanoscale vesicles that can encapsulate neuroprotective agents for targeted therapy.

Research continues to explore these innovative approaches to improve outcomes for neuropathy patients.