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Chronic Meningitis

Disease Details

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Description: Chronic meningitis is an inflammation of the meninges that persists for four weeks or more, often caused by infections, autoimmune disorders, or cancers.
Type: Chronic meningitis is an infectious disease, not typically associated with genetic transmission. It results from prolonged inflammation of the meninges due to various infectious agents, such as bacteria, fungi, or mycobacteria.
Signs And Symptoms: Some of the possible symptoms of chronic meningitis (due to any cause) include headache, nausea and vomiting, fever, and visual impairment. Nuchal rigidity (or neck stiffness with discomfort in trying to move the neck), a classic symptom in acute meningitis, was seen in only 45% of cases of chronic meningitis with the sign being even more rare in non-infectious causes. Other signs associated with chronic meningitis include altered mental status or confusion, and papillary edema (swelling of the optic disc).The headache in chronic meningitis is commonly described as diffuse, poorly localized and constant. Lethargy is a common symptom, with 40% of those also having mental status changes. The inflammation can affect the cranial nerves as they course through the subarachnoid space leading to cranial nerve palsies. Nerve roots may also be affected in chronic meningitis leading to radiculopathy.
Prognosis: The mortality of tuberculosis meningitis is 20-50% even with treatment. A longer duration of presenting symptoms was associated with a higher mortality in tuberculosis meningitis. HIV co-infection, multidrug resistant tuberculosis, or the development of hydrocephalus or focal weakness in tuberculosis meningitis are also associated with a poor prognosis. In those who survive tuberculosis meningitis, 30% have longstanding neurological impairments including seizures, weakness, deafness, blindness, intellectual disability.The mortality rate in cryptococcal meningitis is 25%.
Onset: Chronic meningitis typically has a gradual onset, with symptoms developing over weeks to months.
Prevalence: Chronic meningitis is relatively rare compared to acute meningitis. It accounts for a small percentage of all meningitis cases. Exact prevalence is difficult to determine due to variations in geographic locations and underlying causes.
Epidemiology: Tuberculosis meningitis is more common in children and people who are HIV positive. Cryptococcal meningitis is also more common in those who are HIV positive; with HIV co-infection being present in 95% of cases in low and middle income countries and 80% of cases in high income countries. Those who are immunosuppressed due to organ transplantation also have a higher incidence of cryptococcal meningitis.

== References ==
Intractability: Chronic meningitis can be challenging to treat, but it is not necessarily intractable. The treatment and prognosis depend on the underlying cause, such as infections, autoimmune disorders, or cancer. While some cases may be more difficult to manage, many can be treated effectively with appropriate medical intervention.
Disease Severity: Disease Severity: Chronic meningitis tends to develop more slowly than acute meningitis and can persist for weeks or longer. It often leads to serious, long-term complications if not treated promptly and effectively. The severity can range from moderate to severe, depending on the underlying cause and the timeliness of treatment.
Healthcare Professionals: Disease Ontology ID - DOID:10341
Pathophysiology: The pathogenesis of tuberculosis meningitis involves mycobacterium tuberculosis being shed into the environment via respiratory droplets from an infected person. These droplets are then inhaled to the lungs where the mycobacterium tuberculosis is phagocytosed by macrophages as part of the Th1-helper T cell response and a granuloma forms. Either via disseminated tuberculosis, or by other means, some tubercula gain access to the meninges. Small foci of tuberculous bacilli, known as Rich foci, deposit in the brain, meninges and spinal cord. The tuberculosis bacilli then gain access to the subarachnoid space via the Rich foci and begin the process of meningeal inflammation characteristic of tuberculosis meningitis.
Carrier Status: Chronic meningitis typically does not involve a carrier status. It is a persistent inflammation of the meninges, usually caused by infections with organisms such as Mycobacterium tuberculosis, fungi (like Cryptococcus), or spirochetes (such as Treponema pallidum). Carrier status is more commonly associated with acute forms of meningitis caused by bacteria such as Neisseria meningitidis.
Mechanism: Chronic meningitis is characterized by inflammation of the meninges (the protective membranes covering the brain and spinal cord) that persists for an extended period, typically more than four weeks.

### Mechanism:
1. **Infectious Agents**: Chronic meningitis can be caused by various infectious agents, including bacteria (e.g., Mycobacterium tuberculosis, Treponema pallidum), fungi (e.g., Cryptococcus neoformans), viruses (e.g., HIV), and parasites.
2. **Non-infectious Causes**: It can also stem from non-infectious sources like autoimmune diseases (e.g., lupus), cancer (metastasis to the meninges), or certain medications.
3. **Immune Response**: The persistent presence of an infectious or inflammatory agent leads to a prolonged immune response, resulting in sustained inflammation.

### Molecular Mechanisms:
1. **Pathogen Entry and Persistence**: Pathogens may enter the central nervous system through the bloodstream or direct extension from adjacent structures. Once in the cerebrospinal fluid (CSF), they evade the host immune system, often by residing within host cells or forming biofilms (as is the case with some bacteria).
2. **Immune Modulation**: Chronic pathogens can modulate the immune response to avoid clearance. For example, Mycobacterium tuberculosis can inhibit phagosome-lysosome fusion in macrophages, allowing the bacteria to survive and replicate.
3. **Cytokine Production**: The ongoing presence of pathogens or inflammatory stimuli leads to continuous production of pro-inflammatory cytokines like TNF-α, IL-1β, and IL-6. These cytokines perpetuate the inflammatory response, leading to tissue damage and sustained symptoms.
4. **Persistence of Cells**: Macrophages, T-cells, and other immune cells accumulate in the meninges, contributing to chronic inflammation. Infections like tuberculosis meningitis lead to granuloma formation – clusters of immune cells that aim to contain the infection but also cause tissue damage.
5. **Blood-Brain Barrier Dysfunction**: Chronic inflammation can disrupt the blood-brain barrier, allowing more pathogens and immune cells to enter the CSF and meninges, exacerbating the condition.

Understanding these mechanisms helps in diagnosing, treating, and devising strategies to manage chronic meningitis, including antimicrobial therapy for infections and immunosuppressive treatments for non-infectious causes.
Treatment: Initial diagnostic evaluation often fails to identify a causative organism in chronic infectious meningitis, and empirical therapy may be initiated to prevent significant disability or death. Empiric therapy is indicated in those who are immunocompromized or who are neutropenic. In those who are immune competent, empiric therapy is less well established and is usually initiated on a case by case basis. In those who undergo empirical therapy, treatment involves anti-tuberculosis therapy combined with steroids in areas where tuberculosis is endemic. Anti-fungal empirical therapy is also commonly employed due to fungi's ubiquitous presence and ability to cause opportunistic infections in those who are immunosuppressed. When a causative organism is identified then anti-microbial therapy is targeted specifically to that organism.
Treatment of tuberculosis meningitis consists of a 2 month induction regiment with isoniazid, rifampin, pyrazinamide and ethambutol followed by an extended course (often 7-10 months) of isoniazid and rifampin as maintenance therapy. Isoniazid and pyrazinamide are able to cross the blood-brain barrier. However the duration of maintenance treatment is assumed based on experience with pulmonary tuberculosis, and the optimal duration of therapy in tuberculosis meningitis is not well established. Steroid co-administration is thought to improve outcomes. There is a paucity of information regarding the optimal treatment regiment for multi-drug resistant tuberculosis meningitis (which is by definition resistant to isoniazid and rifampin), but fluoroquinolones and aminoglycosides are able to achieve adequate brain and spinal cord penetration and are often used.The World Health Organization recommends a screen and treat approach with regards to cryptococcal meningitis in those with HIV. All HIV positive people with low CD4+ T cells should undergo cryptococcal serum antigen testing. Those who screen positive for serum cryptococcal antigen should undergo a lumbar puncture followed by treatment if the cerebrospinal fluid contains cryptococcus. Those who cannot undergo a lumbar puncture but screen positive for cryptococcal antigen in the serum should be presumptively treated. Cryptococcal meningitis is treated with 2 weeks of induction therapy using the antifungals amphotericin B and flucytosine followed by 8 weeks of induction therapy with fluconazole and then a prolonged duration (at least one year) of lower dose maintenance fluconazole therapy. Lifelong treatment is required in those with AIDS, however in those who begin anti-retroviral therapy and have CD4 T-cells above 200, therapy can be stopped. Steroid co-therapy is not indicated in cryptococcal meningitis and may worsen outcomes and delay recovery.Hydrocephalus is a common complication in chronic infectious meningitis, including tuberculosis and cryptococcal meningitis. In cases of hydrocephalus, intracranial pressure is controlled by serial therapeutic lumbar punctures (often done daily) until opening pressure normalizes. Diuretics such as furosemide or acetazolamide, osmotic agents such as mannitol, external ventricular drainage, or ventriculoperitoneal shunts may also be used in tuberculosis meningitis to control intracranial pressure.
Compassionate Use Treatment: Chronic meningitis is a persistent inflammatory response of the meninges, the protective tissues covering the brain and spinal cord, lasting for more than four weeks. For compassionate use, off-label, or experimental treatments, the options can vary depending on the underlying cause (bacterial, fungal, viral, or non-infectious).

1. **Compassionate Use Treatments**: These are typically considered when all standard treatments have failed. Options might include:
- **Intravenous immunoglobulin (IVIG)** for immune-mediated forms.
- **Antifungal/Antiviral agents** not typically approved for meningitis but used under compassionate use agreements.

2. **Off-Label Treatments**: These are drugs approved for other indications but used for chronic meningitis due to a lack of effective standard treatments.
- **Rifampin**: Often used in bacterial infections, may be used for chronic bacterial meningitis.
- **Fluconazole, Itraconazole**: Antifungals used off-label for chronic fungal meningitis.

3. **Experimental Treatments**: These are usually under clinical investigation.
- **Biologic agents**: Targeted therapies like TNF inhibitors for chronic inflammatory or autoimmune causes.
- **Novel antivirals**: Under investigation for chronic viral meningitis.
- **Gene therapy**: Research is ongoing for genetic or metabolic causes leading to chronic meningitis.

It's important to consult a specialist experienced in managing chronic meningitis for a tailored treatment approach.
Lifestyle Recommendations: Chronic meningitis refers to a prolonged inflammation of the meninges, the protective membranes covering the brain and spinal cord. Lifestyle recommendations for managing chronic meningitis include:

1. **Healthy Diet:** Consume a balanced and nutritious diet rich in fruits, vegetables, whole grains, lean proteins, and healthy fats to bolster your immune system and overall health.

2. **Hydration:** Ensure adequate fluid intake to keep the body well-hydrated, aiding in overall wellness and recovery.

3. **Rest and Sleep:** Prioritize sufficient rest and good sleep hygiene to support the body's healing processes and maintain strength.

4. **Stress Management:** Implement stress-reducing techniques such as mindfulness meditation, yoga, or deep-breathing exercises to help manage stress levels and improve mental well-being.

5. **Regular Medical Check-ups:** Stay in regular contact with healthcare providers to monitor the condition, manage symptoms, and adjust treatment plans as necessary.

6. **Medication Adherence:** Diligently follow prescribed medication regimens, including antibiotics, antivirals, or antifungals, as guided by a healthcare professional.

7. **Avoid Smoking and Alcohol:** Refrain from smoking and limit alcohol consumption to reduce additional strain on the body and support overall health.

8. **Immunizations:** Stay up-to-date with vaccinations to prevent infections that could lead to or exacerbate meningitis.

9. **Physical Activity:** Engage in moderate physical exercise appropriate to your condition to maintain overall fitness and enhance the immune system, as advised by your healthcare provider.

10. **Infection Control:** Practice good hygiene, such as regular handwashing and avoiding close contact with sick individuals, to prevent further infections.
Medication: Chronic meningitis treatment focuses on addressing the underlying cause:
1. **Bacterial Infections**: Long-term antibiotic therapy tailored to the specific bacteria identified.
2. **Fungal Infections**: Antifungal medications such as amphotericin B or fluconazole, often for extended periods.
3. **Tuberculosis**: A combination of antibiotics like isoniazid, rifampin, pyrazinamide, and ethambutol for several months.
4. **Non-Infectious Causes**: Corticosteroids or immunosuppressive drugs for inflammatory or autoimmune conditions.

The choice of medication depends on the specific pathogen or underlying cause.
Repurposable Drugs: Chronic meningitis is a prolonged inflammation of the meninges and can be caused by various infectious and non-infectious conditions. Specific repurposable drugs for chronic meningitis would depend on the underlying cause, as treatment must target the specific etiology (e.g., bacterial, viral, fungal, or non-infectious). Broadly, some repurposable drugs that may be considered include:

1. **Antibiotics (e.g., Vancomycin, Ceftriaxone)** - for bacterial causes.
2. **Antifungals (e.g., Amphotericin B, Fluconazole)** - for fungal causes.
3. **Antivirals (e.g., Acyclovir)** - for viral causes.
4. **Corticosteroids (e.g., Dexamethasone)** - to reduce inflammation in certain cases.
5. **Immunosuppressants (e.g., Methotrexate)** - for non-infectious, autoimmune causes.

These drugs are subject to careful consideration by a healthcare professional to ensure they are appropriate for the specific type and cause of chronic meningitis.
Metabolites: In chronic meningitis, certain metabolites may be altered due to prolonged inflammation and infection affecting the central nervous system. These can include:

1. **Lactate**: Increased levels in the cerebrospinal fluid (CSF) due to anaerobic glycolysis from inflammatory cells.
2. **Glucose**: Decreased CSF glucose levels as pathogens and inflammatory cells consume glucose.
3. **Protein**: Elevated CSF protein levels due to increased permeability of the blood-brain barrier and the presence of inflammatory proteins.

Metabolite levels are important in the diagnosis and monitoring of chronic meningitis to understand the extent and progression of the disease.
Nutraceuticals: Nutraceuticals are not typically considered a primary or standard treatment for chronic meningitis. Management usually involves identifying and addressing the underlying cause, which could be bacterial, fungal, or another pathogen, and then treating it with appropriate antimicrobial or antifungal medications. Nutraceuticals might be used as supportive care to boost overall health and immunity but should not replace conventional medical treatment. Always consult with a healthcare provider for personalized recommendations.
Peptides: Chronic meningitis involves prolonged inflammation of the meninges, the protective membranes covering the brain and spinal cord. Peptides, which are short chains of amino acids, are being researched for their potential roles in diagnostics and therapeutics related to this condition. For example, certain antimicrobial peptides might be investigated for their ability to target persistent infections that cause chronic meningitis. However, the term "nan" isn't clear in this context and could vary in meaning—perhaps intended to reference nanotechnology or nanomedicine, which may also be explored as innovative approaches to diagnose or treat this disease.