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121-763: Multiple sclerosis ( MS ) is an autoimmune disease resulting in damage to the insulating covers of nerve cells in the brain and spinal cord . As a demyelinating disease , MS disrupts the nervous system's ability to transmit signals , resulting in a range of signs and symptoms , including physical, mental , and sometimes psychiatric problems. Symptoms include double vision , vision loss, eye pain, muscle weakness, and loss of sensation or coordination. MS takes several forms, with new symptoms either occurring in isolated attacks (relapsing forms) or building up over time (progressive forms). In relapsing forms of MS symptoms may disappear completely between attacks, although some permanent neurological problems often remain, especially as

242-566: A clinically isolated syndrome (CIS) over a number of days with 45% having motor or sensory problems, 20% having optic neuritis, and 10% having symptoms related to brainstem dysfunction, while the remaining 25% have more than one of the aforementioned difficulties. With optic neuritis as the most common presenting symptom, people with MS notice sub-acute loss of vision, often associated with pain worsening on eye movement, and reduced color vision. Early diagnosis of MS-associated optic neuritis helps timely initiation of targeted treatments. However, it

363-676: A genetic predisposition , other cases have been associated with infectious triggers or exposure to environmental factors, implying a complex interplay between genes and environment in their etiology. Some of the most common diseases that are generally categorized as autoimmune include coeliac disease , type 1 diabetes , Graves' disease , inflammatory bowel diseases (such as Crohn's disease and ulcerative colitis ), multiple sclerosis , alopecia areata , Addison's disease , pernicious anemia , psoriasis , rheumatoid arthritis , and systemic lupus erythematosus . Diagnosing autoimmune diseases can be challenging due to their diverse presentations and

484-534: A lumbar puncture can provide evidence of chronic inflammation in the central nervous system. The cerebrospinal fluid is tested for oligoclonal bands of IgG on electrophoresis , which are inflammation markers found in 75–85% of people with MS. Several diseases present similarly to MS. Medical professionals use a patient's specific presentation, history, and exam findings to make an individualized differential . Red flags are findings that suggest an alternate diagnosis, although they do not rule out MS. Red flags include

605-432: A 30% chance of developing MS, 5% for a nonidentical twin, 2.5% for a sibling, and an even lower chance for a half sibling. If both parents are affected, the risk in their children is 10 times that of the general population. MS is also more common in some ethnic groups than others. Specific genes linked with MS include differences in the human leukocyte antigen (HLA) system—a group of genes on chromosome 6 that serves as

726-457: A crucial step in triggering autoimmune diseases. The exact mechanisms by which they contribute to disease onset remain to be fully understood. For instance, certain autoimmune conditions like Guillain-Barre syndrome and rheumatic fever are thought to be triggered by infections. Furthermore, analysis of large-scale data has revealed a significant link between SARS-CoV-2 infection (the causative agent of COVID-19 ) and an increased risk of developing

847-437: A demyelinating process such as MS is bilateral internuclear ophthalmoplegia, where the patient experiences double vision when attempting to move their gaze to the right & left. Some 60% or more of MS patients find their symptoms, particularly including fatigue, are affected by changes in body temperature. The main measure of disability and severity is the expanded disability status scale (EDSS), with other measures such as

968-509: A diagnosis of MS. As similarly described before, B-cells can also produce cytokines that induce an inflammatory immune response via activation of autoreactive T-cells. As such, higher levels of these autoreactive B-cells is associated with increased number of lesions & neurodegeneration as well as worse disability. Another cell population that is becoming increasingly implicated in MS are microglia . These cells are resident to & keep watch over

1089-414: A frequently updated set of guidelines used to establish an MS diagnosis. There is no cure for MS. Current treatments aim to mitigate inflammation and resulting symptoms from acute flares and prevent further attacks with disease-modifying medications. Physical therapy and occupational therapy , along with patient-centered symptom management, can help with people's ability to function. The long-term outcome

1210-403: A function that is compromised in autoimmune diseases. In healthy individuals, immune tolerance prevents the immune system from attacking the body's own cells. When this process fails, the immune system may produce antibodies against its own tissues, leading to an autoimmune response. The elimination of self-reactive T cells occurs primarily through a mechanism known as "negative selection" within

1331-473: A genetic component. Some conditions, like lupus and multiple sclerosis, often occur in several members of the same family, indicating a potential hereditary link. Additionally, certain genes have been identified that increase the risk of developing specific autoimmune diseases. Evidence suggests a strong genetic component in the development of autoimmune diseases. For instance, conditions such as lupus and multiple sclerosis frequently appear in multiple members of

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1452-501: A gradual worsening over time without periods of recovery (10–15% of cases). A combination of these two patterns may also occur or people may start in a relapsing and remitting course that then becomes progressive later on. Relapses are usually unpredictable, occurring without warning. Exacerbations rarely occur more frequently than twice per year. Some relapses, however, are preceded by common triggers and they occur more frequently during spring and summer. Similarly, viral infections such as

1573-519: A higher concordance rate among identical twins compared with fraternal twins. For instance, the rate in multiple sclerosis is 35% in identical twins compared to 6% in fraternal twins. There is increasing evidence that certain genes selected during evolution offer a balance between susceptibility to infection and the capacity to avoid autoimmune diseases. For example, variants in the ERAP2 gene provide some resistance to infection even though they increase

1694-523: A history of prior stroke. The relationship between post-stroke depression and PBA is complicated, because the depressive syndrome also occurs with high frequency in stroke survivors. Post-stroke patients with PBA are more depressed than post-stroke patients without PBA, and the presence of a depressive syndrome may exacerbate the weeping side of PBA symptoms. Recent studies suggest that approximately 10% of patients with multiple sclerosis (MS) will experience at least one episode of emotional lability. PBA

1815-514: A pain reliever, and is also used as a recreational drug. Quinidine sulfate affects the way the heart beats, and is generally used in people with certain heart rhythm disorders. It is also used to treat malaria. Quinidine sulfate, as a metabolic inhibitor, "increases plasma levels of dextromethorphan by competitively inhibiting cytochrome P450 2D6, which catalyzes a major biotransformation pathway for dextromethorphan," enabling therapeutic dextromethorphan concentrations. Dextromethorphan/quinidine

1936-787: A patient younger than 15 or older than 60, less than 24 hours of symptoms, involvement of multiple cranial nerves , involvement of organs outside of the nervous system , and atypical lab and exam findings. In an emergency setting, it is important to rule out a stroke or bleeding in the brain. Intractable vomiting, severe optic neuritis, or bilateral optic neuritis raises suspicion for neuromyelitis optica spectrum disorder (NMOSD). Infectious diseases that may look similar to multiple sclerosis include HIV, Lyme disease , and syphilis . Autoimmune diseases include neurosarcoidosis , lupus , Guillain-Barré syndrome , acute disseminated encephalomyelitis , and Behçet's disease . Psychiatric conditions such as anxiety or conversion disorder may also present in

2057-537: A person's own immune system. As briefly detailed in the causes section of this article, MS is currently thought to stem from a failure of the body's immune system to kill off autoreactive T-cells & B-cells. Currently, the T-cell subpopulations that are thought to drive the development of MS are autoreactive CD8+ T-cells, CD4+ helper T-cells, and T H 17 cells. These autoreactive T-cells produce substances called cytokines that induce an inflammatory immune response in

2178-484: A pivotal role in the diagnosis of autoimmune diseases. These tests can identify the presence of certain autoantibodies or other immune markers that indicate a self-directed immune response. In some cases, imaging studies may be used to assess the extent of organ involvement and damage. For example, chest x-rays or CT scans can identify lung involvement in diseases like rheumatoid arthritis or systemic lupus erythematosus, while an MRI can reveal inflammation or damage in

2299-442: A potential causative factor in the development of autoimmune diseases, such as dermatomyositis. Furthermore, exposure to pesticides has been linked with an increased risk of developing rheumatoid arthritis. Vitamin D, on the other hand, appears to play a protective role, particularly in older populations, by preventing immune dysfunctions. Infectious agents are also being increasingly recognized for their role as T cell activators —

2420-440: A recent investigation estimate the prevalence of PBA associated with traumatic brain injury to exceed more than 55% of survivors. Education of patients, families, and caregivers is an important component of the appropriate treatment of PBA. Crying associated with PBA may be incorrectly interpreted as depression; laughter may be embarrassing, anger can be debilitating. It is therefore critical for families and caregivers to recognize

2541-728: A relatively high risk and that live closer to the equator such as Sardinians , inland Sicilians , Palestinians , and Parsi . MS symptoms may increase if body temperature is dysregulated. Fatigue is particularly affected. Smoking may be an independent risk factor for MS. Stress may also be a risk factor, although the evidence to support this is weak. Association with occupational exposures and toxins —mainly organic solvents —has been evaluated, but no clear conclusions have been reached. Vaccinations were studied as causal factors; most studies, though, show no association. Several other possible risk factors, such as diet and hormone intake, have been evaluated, but evidence on their relation with

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2662-464: A role in MS onset, although EBV alone may be insufficient to cause it. The nuclear antigen of EBV , which is the most consistent marker of EBV infection across all strains, has been identified as a direct source of autoreactivity in the human body. These antigens appear more likely to promote autoimmunity vitamin D-deficient persons. The exact nature of this relationship is poorly understood. MS

2783-400: A severe change of mental status, as in traumatic brain injury they often have insight into their problem and judge their emotional displays as inappropriate and out of character. The clinical effect of PBA can be severe, with unremitting and persistent symptoms that can be disabling to patients, and may significantly affect quality of life for caregivers. While not as profoundly disabling as

2904-408: A similar way. Other rare diseases on the differential include CNS lymphoma , congenital leukodystrophies , and anti-MOG-associated myelitis . Autoimmune disease An autoimmune disease is a condition that results from an anomalous response of the adaptive immune system , wherein it mistakenly targets and attacks healthy, functioning parts of the body as if they were foreign organisms. It

3025-424: A small proportion of those infected later develop MS. A study of more than 10 million US military members compared 801 people who developed MS to 1,566 matched controls who did not. The study found a 32-fold increased risk of MS development following EBV infection. It did not find an increased risk after infection with other viruses, including the similar cytomegalovirus . These findings strongly suggest that EBV plays

3146-597: A symptom of hyperthyroidism , Graves' disease , or hypothyroidism in combination with depression. PBA has also been observed in association with a variety of other brain disorders, including brain tumors , Wilson's disease , syphilitic pseudobulbar palsy , and various encephalitides . Rarer conditions associated with PBA include gelastic epilepsy , dacrystic epilepsy, central pontine myelinolysis , olivopontinocerebellar atrophy , lipid storage diseases , chemical exposure (e.g., nitrous oxide and insecticides ), fou rire prodromique , and Angelman syndrome . It

3267-440: A thorough evaluation of the patient's medical history and a comprehensive physical examination. Clinicians often pay close attention to the patient's symptoms, family history of autoimmune diseases, and any exposure to environmental factors that might trigger an autoimmune response. The physical examination can reveal signs of inflammation or organ damage, which are common features of autoimmune disorders. Laboratory testing plays

3388-426: A total of 326 participants received one of three dose options. "METHODS: In a 12-week randomized, double-blind trial, ALS and MS patients with clinically significant PBA" were given a twice-daily dose of one of the following: 283 patients (86.8%) completed the study. The number of PBA episodes (laughing, crying or aggressive outbursts) were 47% and 49% lower (based on the trial's outcome measures), respectively, for

3509-427: A wide range of new-onset autoimmune diseases. Women typically make up some 80% of autoimmune disease patients. Whilst many proposals have been made for the cause of this high weighting, no clear explanation is available. A possible role for hormonal factors has been suggested. For example, some autoimmune diseases tend to flare during pregnancy (possibly as an evolutionary mechanism to increase health protection for

3630-456: Is a combination of these two generic drugs, and is the first FDA-approved drug for the treatment of PBA, approved on October 29, 2010. In the pivotal multicenter study that led to its approval, the "Objectives...[were] to evaluate the safety, tolerability, and efficacy of two different doses of AVP-923 [Dextromethorphan/quinidine combination]...when compared to placebo." The conditions and results of that study are as follows: At one study site,

3751-410: Is a known risk factor for developing MS. Inversely, those who live in areas of relatively higher sun exposure and subsequently increased UVB radiation have a decreased risk of developing MS. As of 2019, the north–south gradient of incidence is still present and is increasing. On the other hand, MS is more common in regions with northern European populations, so the geographic variation may simply reflect

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3872-550: Is a symptom of ALS that many patients are unaware of and do not receive information about from their physician. One study of 301 consecutive cases in a clinic setting reported a 5% prevalence. PBA occurred in patients with more severe head injury , and coincided with other neurological features suggestive of pseudobulbar palsy. The Brain Injury Association of America (BIAA) indicates that approximately 80% of survey respondents experience symptoms of PBA. Results from

3993-421: Is a systemic autoimmune disease that affects multiple organs, including the skin, joints, kidneys, and the nervous system. It is characterized by a widespread loss of immune tolerance. The disease is characterized by periods of flares and remissions, and symptoms range from mild to severe. Women, especially those of childbearing age, are disproportionately affected. Type 1 diabetes is a condition resulting from

4114-478: Is an autoimmune disease with a combination of genetic and environmental causes underlying it. Both T-cells and B-cells are involved, although T-cells are often considered to be the driving force of the disease. The causes of the disease are not fully understood. The Epstein-Barr Virus (EBV) has been shown to be directly present in the brain of most cases of MS and the virus is transcriptionally active in infected cells. EBV nuclear antigens are believed to be involved in

4235-427: Is associated with an increased risk of central nervous system cancer, primarily in the brain. Rheumatoid arthritis (RA) primarily targets the joints, causing persistent inflammation that results in joint damage and pain. It is often symmetrical, meaning that if one hand or knee has it, the other one does too. RA can also affect the heart, lungs, and eyes. Additionally, the chronic inflammation and over-activation of

4356-492: Is correlated with lymphoproliferative disorders . Graves' disease is a condition characterized by development of autoantibodies to thyroid-stimulating hormone receptors. The binding of the autoantibodies to the receptors results in unregulated production and release of thyroid hormone , which can lead to stimulatory effects such as rapid heart rate, weight loss, nervousness, and irritability. Other symptoms more specific to Graves' disease include bulging eyes and swelling of

4477-477: Is crucial to adhere to established diagnostic criteria when treating optic neuritis due to the broad range of alternative causes, such as neuromyelitis optica spectrum disorder (NMOSD), and other autoimmune or infectious conditions. The course of symptoms occurs in two main patterns initially: either as episodes of sudden worsening that last a few days to months (called relapses , exacerbations, bouts, attacks, or flare-ups) followed by improvement (85% of cases) or as

4598-595: Is difficult to predict; better outcomes are more often seen in women, those who develop the disease early in life, those with a relapsing course, and those who initially experienced few attacks. MS is the most common immune-mediated disorder affecting the central nervous system (CNS). Nearly one million people in the United States had MS in 2022, and in 2020, about 2.8 million people were affected globally, with rates varying widely in different regions and among different populations. The disease usually begins between

4719-529: Is equipped with several mechanisms to maintain a delicate balance between defending against foreign invaders and protecting its own cells. To achieve this, it generates both T cells and B cells , which are capable of reacting with self-proteins. However, in a healthy immune response, self-reactive cells are generally either eliminated before they become active, rendered inert via a process called anergy, or their activities are suppressed by regulatory cells. A familial tendency to develop autoimmune diseases suggests

4840-442: Is estimated that over 80 recognized types of autoimmune diseases exist, this section provides an overview of some of the most common and well-studied forms. Coeliac disease is an immune reaction to eating gluten , a protein found in wheat , barley , and rye . For those with the disease, eating gluten triggers an immune response in the small intestine , leading to damage on the villi , small fingerlike projections that line

4961-429: Is estimated that there are more than 80 recognized autoimmune diseases, with recent scientific evidence suggesting the existence of potentially more than 100 distinct conditions. Nearly any body part can be involved. Autoimmune diseases are a separate class from autoinflammatory diseases . Both are characterized by an immune system malfunction which may cause similar symptoms, such as rash, swelling, or fatigue, but

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5082-421: Is generally associated with later stages of the disease (chronic progressive phase). PBA in MS patients is associated with more severe intellectual deterioration, physical disability, and neurological disability. A study designed specifically to survey for prevalence found that 49% of patients with amyotrophic lateral sclerosis (ALS) also had PBA. PBA does not appear to be associated with duration of ALS. It

5203-428: Is hypothesized that these primary neurologic injuries and diseases affect chemical signaling in the brain, which in turn disrupts the neurologic pathways that control emotional expression. PBA is one of the most frequently reported post-stroke behavioral disorders , with a range of reported prevalence rates from 28% to 52%. The higher prevalence rates tend to be reported in stroke patients who are older or who have

5324-434: Is more advanced, walking difficulties lead to higher risk of falling. Difficulties thinking and emotional problems such as depression or unstable mood are also common. The primary deficit in cognitive function that people with MS experience is slowed information-processing speed, with memory also commonly affected, and executive function less commonly. Intelligence, language, and semantic memory are usually preserved, and

5445-402: Is not considered a hereditary disease , but several genetic variations have been shown to increase its risk. Some of these genes appear to have higher expression levels in microglial cells than expected by chance. The probability of developing MS is higher in relatives of an affected person, with a greater risk among those more closely related. An identical twin of an affected individual has

5566-447: Is provided in the pathophysiology section of this article as well as the standalone article on the pathophysiology of MS . Early evidence suggested the association between several viruses with human demyelinating encephalomyelitis , and the occurrence of demyelination in animals caused by some viral infections. One such virus, Epstein-Barr virus (EBV), can cause infectious mononucleosis and infects about 95% of adults, though only

5687-509: Is responsible for the immune system's central tolerance, where autoreactive T-cells are killed without being released into circulation. A similar mechanism kills autoreactive B-cells in the bone marrow. Some autoreactive T-cells & B-cells may escape these defense mechanisms, which is where peripheral immune tolerance defenses take action by preventing them from causing disease. However, these additional lines of defense can still fail. Further detail on immune dysregulation's contribution to MS risk

5808-441: Is still under investigation; the primary pathogenic mechanisms of PBA remain controversial. One hypothesis, established by early researchers such as Wilson and Oppenheim, placed emphasis on the role of the corticobulbar pathways in modulating emotional expression in a top-down model, and theorized that PBA occurs when bilateral lesions in the descending corticobulbar tract cause failure of voluntary control of emotion, which leads to

5929-468: Is the most commonly used method of diagnosis with the Schumacher and Poser criteria being of mostly historical significance. The McDonald criteria states that patients with multiple sclerosis should have lesions which are disseminated in time (DIT) and disseminated in space (DIS), i.e. lesions which have appeared in different areas in the brain and at different times. Below is an abbreviated outline of

6050-414: Is typically diagnosed based on the presenting signs and symptoms, in combination with supporting medical imaging and laboratory testing. It can be difficult to confirm, especially early on, since the signs and symptoms may be similar to those of other medical problems. The McDonald criteria , which focus on clinical, laboratory, and radiologic evidence of lesions at different times and in different areas,

6171-465: The CNS , a person with MS can have almost any neurological symptom or sign referable to it. Fatigue is one of the most common symptoms of MS. Roughly 65% of people with MS experience fatigue symptomatology, and of these, some 15–40% report fatigue as their most disabling MS symptom. Autonomic , visual, motor, and sensory problems are also among the most common symptoms. The specific symptoms depend on

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6292-475: The common cold , influenza , or gastroenteritis increase their risk. Stress may also trigger an attack. Many events do not to affect rates of relapse requiring hospitalization including vaccination , breast feeding , physical trauma, and Uhthoff's phenomenon . Many people with MS who become pregnant experience lower symptoms During the first months after delivery, the risk increases. Overall, pregnancy does not seem to influence long-term disability. MS

6413-402: The equator (e.g. those who live in northern regions of the world), although exceptions exist. The cause of this geographical pattern is not clear, although exposure to ultraviolet B (UVB) radiation and vitamin D levels may be possible explanations. For example, those who live in northern regions of the world have less exposure to UVB radiation and subsequently lower levels of vitamin D, which

6534-463: The major histocompatibility complex (MHC). The contribution of HLA variants to MS susceptibility has been known since the 1980s, and it has also been implicated in the development of other autoimmune diseases, such as type 1 diabetes and systemic lupus erythematosus . The most consistent finding is the association between higher risk MS development and the MHC allele DR15 , which is present in 30% of

6655-450: The multiple sclerosis functional composite being increasingly used in research. EDSS is also correlated with falls in people with MS. While it is a popular measure, EDSS has been criticized for some of its limitations, such as overreliance on walking. MS may have a prodromal phase in the years leading up to its manifestation, characterized by psychiatric issues, cognitive impairment, and increased use of healthcare. 85% of cases begin as

6776-441: The 2017 McDonald Criteria for diagnosis of MS. As of 2017, no single test (including biopsy) can provide a definitive diagnosis. Magnetic resonance imaging (MRI) of the brain and spine may show areas of demyelination (lesions or plaques). Gadolinium can be administered intravenously as a contrast agent to highlight active plaques, and by elimination, demonstrate the existence of historical lesions not associated with symptoms at

6897-498: The 2019 movie Parasite , the character Ki-woo sustains head trauma, and although it is not clearly mentioned that he's affected by pseudobulbar affect, he mentions not being able to stop laughing when thinking about all the events that occur in the movie. In the 2020 movie Naan Sirithal , the character Gandhi ( Hiphop Tamizha Adhi ) suffers from pseudobulbar affect due to all the stress he suffers from various parts of his life gets accumulated and starts to laugh uncontrollably. In

7018-498: The CNS, leading to the development of the disease. More recently, however, the role of autoreactive B-cells has been elucidated. Evidence of their contribution to the development of MS is implicated through the presence of oligoclonal IgG bands (antibodies produced by B-cells) in the CSF of patients with MS. The presence of these oligoclonal bands has been used as supportive evidence in clinching

7139-669: The CNS, responding to pathogens by shifting between pro- & anti-inflammatory states. Microglia have been shown to be involved in the formation of MS lesions and have been shown to be involved in other diseases that primarily affect the CNS white matter. Although, because of their ability to switch between pro- & anti-inflammatory states, microglia have also been shown to be able to assist in remyelination & subsequent neuron repair. As such, microglia are thought to be participating in both acute & chronic MS lesions, with 40% of phagocytic cells in early active MS lesions being proinflammatory microglia. The name multiple sclerosis refers to

7260-507: The Emotions in Man and Animals by Charles Darwin was published in 1872. In Chapter VI, "Special Expressions of Man: Suffering and Weeping", Darwin discusses cultural variations in the acceptability of weeping and the wide differences in individual responses to suffering. The chapter contains the following sentence: We must not, however, lay too much stress on the copious shedding of tears by

7381-498: The U.S. and Northern European population. Other loci exhibit a protective effect, such as HLA-C554 and HLA-DRB1 *11 . HLA differences account for an estimated 20 to 60% of the genetic predisposition . Genome-wide association studies have revealed at least 200 MS-associated variants outside the HLA locus . The prevalence of MS from a geographic standpoint resembles a gradient, with it being more common in people who live farther from

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7502-443: The adjacent Table. In some cases, depressed mood and PBA may co-exist. Since depression is one of the most common emotional changes in patients with neurodegenerative disease or post-stroke sequelae, it is often comorbid with PBA. Comorbidity implies that depression is distinct from PBA and is not necessary for, nor does it exclude, a diagnosis of PBA. The specific pathophysiology involved in this frequently debilitating condition

7623-472: The ages of 20 and 50 and is twice as common in women as in men. MS was first described in 1868 by French neurologist Jean-Martin Charcot . The name "multiple sclerosis " is short for multiple cerebro-spinal sclerosis , which refers to the numerous glial scars (or sclerae – essentially plaques or lesions) that develop on the white matter of the brain and spinal cord. As MS lesions can affect any part of

7744-619: The appearance of uncontrollable emotions is commonly associated with many additional neurological disorders such as attention deficit hyperactivity disorder , Parkinson's disease , cerebral palsy , autism , epilepsy , and migraines . This may lead to avoidance of social interactions for the patient, which in turn impairs their coping mechanisms and their careers. PBA may often be misdiagnosed as clinical depression or bipolar disorder ; however, many clear distinctions exist. In depressive and bipolar disorders , crying, anger or laughter are typically indicative of mood , whereas

7865-470: The bacterium that causes strep throat , Streptococcus pyogenes , might trigger rheumatic fever , an autoimmune response affecting the heart. Similarly, some studies propose a link between the Epstein–Barr virus , responsible for mononucleosis, and the subsequent development of multiple sclerosis or lupus. Another area of interest is the immune system's ability to distinguish between self and non-self,

7986-492: The body's immune system mistakenly attacking its own cells and tissues, causing inflammation and damage. However, due to the broad range of autoimmune diseases, the specific presentation of symptoms can significantly vary based on the type of disease, the organ systems affected, and individual factors such as age, sex, hormonal status, and environmental influences. An individual may simultaneously have more than one autoimmune disease (known as polyautoimmunity), further complicating

8107-497: The body's self-molecules. This phenomenon, known as molecular mimicry , can lead to cross-reactivity, where the immune response to such infections inadvertently results in the production of antibodies that also react with self-antigens. An example of this is Guillain–Barré syndrome , in which antibodies generated in response to a C. jejuni infection also react with the gangliosides in the myelin sheath of peripheral nerve axons. Diagnosing autoimmune disorders can be complex due to

8228-419: The body. The peripheral nervous system is rarely involved. To be specific, MS involves the loss of oligodendrocytes , the cells responsible for creating and maintaining a fatty layer—known as the myelin sheath—which helps the neurons carry electrical signals (action potentials). This results in a thinning or complete loss of myelin, and as the disease advances, the breakdown of the axons of neurons. When

8349-733: The brain and spinal cord in multiple sclerosis. Given the variety and nonspecific nature of symptoms that can be associated with autoimmune diseases, differential diagnosis—determining which of several diseases with similar symptoms is causing a patient's illness—is an important part of the diagnostic process. This often involves ruling out other potential causes of symptoms, such as infections, malignancies, or genetic disorders. Labile affect The pseudobulbar affect, also referred to as emotional lability , should not be confused with depression that stems from emotional instability – affective dysregulation – commonly seen in mental illnesses and certain personality disorders. The cardinal feature of

8470-461: The brain. Gadolinium cannot cross a normal BBB, so gadolinium-enhanced MRI is used to show BBB breakdowns. The pathophysiology and mechanisms causing MS fatigue are not well understood. MS fatigue can be affected by body heat, and this may differentiate MS fatigue from other primary fatigue. Fatigability (loss of strength) may increase perception of fatigue, but the two measures warrant independent assessment in clinical studies. Multiple sclerosis

8591-923: The cardinal cause or mechanism of the diseases are different. A key difference is a malfunction of the innate immune system in autoinflammatory diseases, whereas in autoimmune diseases there is a malfunction of the adaptive immune system . Symptoms of autoimmune diseases can significantly vary, primarily based on the specific type of the disease and the body part that it affects. Symptoms are often diverse and can be fleeting, fluctuating from mild to severe, and typically comprise low-grade fever , fatigue , and general malaise . However, some autoimmune diseases may present with more specific symptoms such as joint pain , skin rashes (e.g., urticaria ), or neurological symptoms. The exact causes of autoimmune diseases remain unclear and are likely multifactorial, involving both genetic and environmental influences. While some diseases like lupus exhibit familial aggregation, suggesting

8712-422: The child), when hormone levels are high, and improve after menopause, when hormone levels decrease. Women may also naturally have autoimmune disease trigger events in puberty and pregnancy. Under-reporting by men may also be a factor, as men may interact less with the health system than women. Certain viral and bacterial infections have been linked to autoimmune diseases. For instance, research suggests that

8833-442: The complexity and multifaceted nature of these conditions. Various environmental triggers are identified, some of which include: Chemicals, which are either a part of the immediate environment or found in drugs, are key players in this context. Examples of such chemicals include hydrazines , hair dyes , trichloroethylene , tartrazines , hazardous wastes, and industrial emissions. Ultraviolet radiation has been implicated as

8954-399: The context in which they occur. Where patients have significant cognitive deficits (e.g., Alzheimer's ) it can be unclear whether it is true PBA as opposed to a grosser form of emotional dysregulation, but patients with intact cognition often report the symptom as disturbing. Patients report that their episodes are at best only partially amenable to voluntary control, and unless they experience

9075-480: The crying, anger or other emotional displays in PBA is minimal or nonexistent, whereas for those with depression, the emotional expression (typically crying) can be modulated by the situation. Similarly, the trigger for episodes of crying in patients with PBA may be nonspecific, minimal or inappropriate to the situation, but in depression the stimulus is specific to the mood-related condition. These differences are outlined in

9196-447: The development and progression of various autoimmune diseases, either directly or as catalysts. Current research suggests that up to seventy percent of autoimmune diseases could be attributed to environmental influences, which encompass an array of elements such as chemicals, infectious agents, dietary habits, and gut dysbiosis. However, a unifying theory that definitively explains the onset of autoimmune diseases remains elusive, emphasizing

9317-424: The diagnosis of an autoimmune condition, often in conjunction with tests for specific biological markers, but also help monitor disease progression and response to treatment. Ultimately, due to the diverse nature of autoimmune diseases, a multidimensional approach is often needed for the management of these conditions, taking into consideration the variety of symptoms and their impacts on individuals' lives. While it

9438-430: The diagnostic criteria established for any one connective tissue disease. Some 30–40% transition to a specific connective tissue disease over time. The exact causes of autoimmune diseases remain largely unknown; however, research has suggested that a combination of genetic, environmental, and hormonal factors, as well as certain infections, may contribute to the development of these disorders. The human immune system

9559-466: The disease advances. In progressive forms of MS, bodily function slowly deteriorates once symptoms manifest and will steadily worsen if left untreated. While its cause is unclear, the underlying mechanism is thought to be due to either destruction by the immune system or inactivation of myelin-producing cells. Proposed causes for this include immune dysregulation, genetics , and environmental factors, such as viral infections . The McDonald criteria are

9680-445: The disease is "sparse and unpersuasive". Gout occurs less than would be expected and lower levels of uric acid have been found in people with MS. This has led to the theory that uric acid is protective, although its exact importance remains unknown. Obesity during adolescence and young adulthood is a risk factor for MS. Multiple sclerosis is an autoimmune disease, primarily mediated by T-cells. The three main characteristics of MS are

9801-718: The disinhibition, or release, of laughing/crying centers in the brainstem. Other theories implicate the prefrontal cortex . PBA is a condition that occurs secondary to neurological disease or brain injury, and is thought to result from disruptions of neural networks that control the generation and regulation of motor output of emotions. PBA is most commonly observed in people with neurologic injuries such as traumatic brain injury (TBI) and stroke , and neurologic diseases such as dementias including Alzheimer's disease , attention deficit hyperactivity disorder (ADHD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). It has been reported as

9922-431: The disorder is a pathologically lowered threshold for exhibiting the behavioral response of laughter, crying, anger or all of the above. An affected individual exhibits episodes of laughter, crying, anger or a combination of these without an apparent motivating stimulus or in response to stimuli that would not have elicited such an emotional response before the onset of their underlying neurologic disorder. In some patients,

10043-617: The drug-combination options than for the placebo. The "mean CNS-LS scores" decreased by 8.2 points for both drug-combination options, vs a decrease of 5.7 points for the placebo. Overall, the trial showed a statistically significant benefit from taking a combination of dextromethorphan and quinidine, with both dosages being safe and well tolerated. For a secondary objective measuring a participant's "perceived health status...measuring eight health concepts: vitality, physical functioning, bodily pain, general health perceptions, physical role-, emotional role-, social role functioning, and mental health,"

10164-402: The early 1900s, and since then, advancements in understanding and management of these conditions have been substantial, though much more is needed to fully unravel their complex etiology and pathophysiology . Autoimmune diseases represent a vast and diverse category of disorders that, despite their differences, share some common symptomatic threads. These shared symptoms occur as a result of

10285-467: The emotional response is exaggerated in intensity but is provoked by a stimulus with an emotional valence congruent with the character of the emotional display. For example, a sad stimulus provokes a pathologically exaggerated weeping response instead of a sigh, which the patient normally would have exhibited in that particular instance. However, in some other patients, the character of the emotional display can be incongruent with, and even contradictory to,

10406-556: The emotional valence of the provoking stimulus or may be incited by a stimulus with no clear valence. For example, a patient may laugh in response to sad news or cry in response to stimuli with no emotional undertone, or, once provoked, the episodes may switch from laughing to crying or vice versa. The symptoms of PBA can be severe, with persistent and unremitting episodes. Characteristics include: Many people with neurologic disorders exhibit uncontrollable episodes of laughing, crying, or anger that are either exaggerated or contradictory to

10527-400: The formation of lesions in the central nervous system (also called plaques), inflammation, and the destruction of myelin sheaths of neurons . These features interact in a complex and not yet fully understood manner to produce the breakdown of nerve tissue, and in turn, the signs and symptoms of the disease. Damage is believed to be caused, at least in part, by attack on the nervous system by

10648-450: The gastrointestinal tract and some lymphoproliferative cancers. Multiple sclerosis (MS) is a neurodegenerative disease in which the immune system attacks myelin , a protective covering of nerve fibers in the central nervous system, causing communication problems between the brain and the rest of the body. Symptoms can include fatigue, difficulty walking, numbness or tingling, muscle weakness, and problems with coordination and balance. MS

10769-538: The global distribution of these high-risk populations. A relationship between season of birth and MS lends support to this idea, with fewer people born in the Northern Hemisphere in November compared to May being affected later in life. Environmental factors may play a role during childhood, with several studies finding that people who move to a different region of the world before the age of 15 acquire

10890-404: The higher dosage showed improvement, especially on measures of social functioning and mental health. Prevalence estimates place the number of people with PBA between 1.5 and 2 million in the United States alone, which would be less than 1% of the U.S. population even at the high end of the estimate. Some argue that the number is probably higher and that clinicians underdiagnose PBA. However,

11011-547: The idea that the symptoms seemed similar to those caused by a bulbar lesion (that is, a lesion in the medulla oblongata ). Terms such as forced crying, involuntary crying, pathological emotionality, and emotional incontinence have also been used, although less frequently. Arthur Fleck, the central character of the 2019 film Joker , displays signs of pseudobulbar affect, which are said to be what Joaquin Phoenix used as inspiration for his character's signature laugh. In

11132-452: The immune system attacking insulin-producing beta cells in the pancreas , leading to high blood sugar levels. Symptoms include increased thirst , frequent urination , and unexplained weight loss . It is most commonly diagnosed in children and young adults. Undifferentiated connective tissue disease occurs when people have features of connective tissue disease, such as blood test results and external characteristics, but do not fulfill

11253-406: The immune system creates an environment that favors further malignant transformation of other cells, perhaps explaining the associations with cancer of the lungs and skin as well as the increased risk of other hematologic cancers, none of which are directly affected by the inflammation of joints. Psoriasis is a skin condition characterized by the rapid buildup of skin cells, leading to scaling on

11374-495: The insane, as being due to the lack of all restraint; for certain brain-diseases, as hemiplegia, brain-wasting, and senile decay, have a special tendency to induce weeping. Historically, there have been a variety of terms used for the disorder, including pseudobulbar affect, pathological laughter and crying, emotional lability, emotionalism, emotional dysregulation, or more recently, involuntary emotional expression disorder. The term pseudobulbar ( pseudo- + bulbar ) came from

11495-419: The level of cognitive impairment varies considerably between people with MS. Uhthoff's phenomenon , a worsening of symptoms due to exposure to higher-than-usual temperatures, and Lhermitte's sign , an electrical sensation that runs down the back when bending the neck, are particularly characteristic of MS, although may not always be present. Another presenting manifestation that is rare but highly suggestive of

11616-624: The location and type of autoimmune response. For instance, in rheumatoid arthritis, an autoimmune disease primarily affecting the joints, symptoms typically include joint pain, swelling, and stiffness. On the other hand, type 1 diabetes, which results from an autoimmune attack on the insulin-producing cells of the pancreas, primarily presents with symptoms related to high blood sugar, such as increased thirst, frequent urination, and unexplained weight loss. Commonly affected areas in autoimmune diseases include blood vessels, connective tissues, joints, muscles, red blood cells, skin, and endocrine glands such as

11737-658: The locations of the lesions within the nervous system, and may include focal loss of sensitivity or changes in sensation in the limbs, such as feeling tingling, pins and needles, or numbness; limb motor weakness/pain, blurred vision , pronounced reflexes , muscle spasms , difficulty with ambulation (walking), difficulties with coordination and balance ( ataxia ); problems with speech or swallowing , visual problems ( optic neuritis manifesting as eye pain & vision loss, or nystagmus manifesting as double vision ), fatigue, and bladder and bowel difficulties (such as urinary or fecal incontinence or retention), among others. When MS

11858-407: The loss of myelin, or they may cause the axon to break down completely. The blood–brain barrier (BBB) is a part of the capillary system that prevents the entry of T cells into the central nervous system. It may become permeable to these types of cells secondary to an infection by a virus or bacteria. After it repairs itself, typically once the infection has cleared, T cells may remain trapped inside

11979-420: The lower legs . Inflammatory bowel disease encompasses conditions characterized by chronic inflammation of the digestive tract, including Crohn's disease and ulcerative colitis . In both cases, individuals lose immune tolerance for normal bacteria present in the gut microbiome . Symptoms include severe diarrhea, abdominal pain, fatigue, and weight loss. Inflammatory bowel disease is associated with cancers of

12100-452: The moment of the evaluation. Central vein signs (CVSs) have been proposed as a good indicator of MS in comparison with other conditions causing white lesions. One small study found fewer CVSs in older and hypertensive people. Further research on CVS as a biomarker for MS is ongoing. Only postmortem MRI allows visualization of sub-millimetric lesions in cortical layers and in the cerebellar cortex. Testing of cerebrospinal fluid obtained from

12221-400: The myelin is lost, a neuron can no longer effectively conduct electrical signals. A repair process, called remyelination , takes place in early phases of the disease, but the oligodendrocytes are unable to completely rebuild the cell's myelin sheath. Repeated attacks lead to successively less effective remyelinations, until a scar-like plaque is built up around the damaged axons. These scars are

12342-543: The new region's risk of MS. If migration takes place after age 15, the persons retain the risk of their home country. Some evidence indicates that the effect of moving may still apply to people older than 15. There are some exceptions to the above mentioned geographic pattern. These include ethnic groups that are at low risk and that live far from the equator such as the Sami , Amerindians , Canadian Hutterites , New Zealand Māori , and Canada's Inuit , as well as groups that have

12463-498: The origin of the symptoms and during an attack magnetic resonance imaging (MRI) often shows more than 10 new plaques. This could indicate that some number of lesions exist, below which the brain is capable of repairing itself without producing noticeable consequences. Another process involved in the creation of lesions is an abnormal increase in the number of astrocytes due to the destruction of nearby neurons. A number of lesion patterns have been described. Apart from demyelination,

12584-527: The other sign of the disease is inflammation . Fitting with an immunological explanation, the inflammatory process is caused by T cells , a kind of lymphocytes that plays an important role in the body's defenses. T cells gain entry into the brain as a result of disruptions in the blood–brain barrier . The T cells recognize myelin as foreign and attack it, explaining why these cells are also called "autoreactive lymphocytes". The attack on myelin starts inflammatory processes, which trigger other immune cells and

12705-579: The overactive immune response. In certain cases, intravenous immunoglobulin may be administered to regulate the immune system. Despite these treatments often leading to symptom improvement, they usually do not offer a cure and long-term management is often required. In terms of prevalence, a UK study found that 10% of the population were affected by an autoimmune disease. Women are more commonly affected than men. Autoimmune diseases predominantly begin in adulthood, although they can start at any age. The initial recognition of autoimmune diseases dates back to

12826-424: The pathogenesis of multiple sclerosis, but not all people with MS have signs of EBV infection. Dozens of human peptides have been identified in different cases of the disease, and while some have plausible links to infectious organisms or known environmental factors, others do not. Failure of both central and peripheral nervous system clearance of autoreactive immune cells is implicated in MS development. The thymus

12947-434: The pathological displays of crying which occur in PBA are often in contrast to the underlying mood, or greatly in excess of the mood or eliciting stimulus. In addition, a key to differentiating depression from PBA is duration: PBA episodes are sudden, occurring in an episodic manner, while crying in depression is a more sustained presentation and closely relates to the underlying mood state. The level of control that one has over

13068-456: The pathological nature of PBA and the reassurance that this is an involuntary syndrome that is manageable. Traditionally, antidepressants such as sertraline , fluoxetine , citalopram , nortriptyline and amitriptyline have been prescribed with some efficacy. Dextromethorphan hydrobromide affects the signals in the brain that trigger the cough reflex. It is used as a cough suppressant, although it can sometimes be used, medicinally, as

13189-471: The physical symptoms of the most common diseases that cause it (such as ALS ), PBA may significantly influence individuals' social functioning and their relationships with others. Such sudden, frequent, extreme, uncontrollable emotional outbursts may lead to social withdrawal and interfere with activities of daily living, social and professional pursuits, and reduce overall healthcare. For example, patients with ALS and MS are often cognitively normal. However,

13310-449: The prevalence estimate of 2 million is based on an online survey. Self-selected computer-savvy patients in at-risk groups evaluated their own symptoms and submitted their self-diagnoses. No doctor or clinic confirmed the data. Motivation to participate could have been influenced by the presence of symptoms, which would have skewed the results. The actual prevalence could very well be quite a bit lower than estimated. The Expression of

13431-499: The release of soluble factors like cytokines and antibodies . A further breakdown of the blood-brain barrier, in turn, causes a number of other damaging effects, such as swelling , activation of macrophages , and more activation of cytokines and other destructive proteins. Inflammation can potentially reduce transmission of information between neurons in at least three ways. The soluble factors released might stop neurotransmission by intact neurons. These factors could lead to or enhance

13552-675: The risk of autoimmunity (positive selection). In contrast, variants in the TYK2 gene protect against autoimmune diseases but increase the risk of infection (negative selection). This suggests the benefits of infection resistance may outweigh the risks of autoimmune diseases, particularly given the historically high risk of infection. Several experimental methods such as the genome-wide association studies have been used to identify genetic risk variants that may be responsible for diseases such as type 1 diabetes and rheumatoid arthritis. A significant number of environmental factors have been implicated in

13673-538: The same family, signifying a potential hereditary link. Furthermore, certain genes have been identified that augment the risk of developing specific autoimmune diseases. Experimental methods like genome-wide association studies have proven instrumental in pinpointing genetic risk variants potentially responsible for autoimmune diseases. For example, these studies have been used to identify risk variants for diseases such as type 1 diabetes and rheumatoid arthritis. In twin studies, autoimmune diseases consistently demonstrate

13794-403: The scars (sclerae – better known as plaques or lesions) that form in the nervous system. These lesions most commonly affect the white matter in the optic nerve , brain stem , basal ganglia , and spinal cord , or white matter tracts close to the lateral ventricles . The function of white matter cells is to carry signals between grey matter areas, where the processing is done, and the rest of

13915-484: The skin's surface. Inflammation and redness around the scales is common. Some individuals with psoriasis also develop psoriatic arthritis , which causes joint pain, stiffness, and swelling. Sjögren syndrome is a long-term autoimmune disease that affects the body's moisture-producing glands (lacrimal and salivary), and often seriously affects other organ systems, such as the lungs, kidneys, and nervous system. Systemic lupus erythematosus , referred to simply as lupus,

14036-457: The small intestine and promote nutrient absorption. This explains the increased risk of gastrointestinal cancers , as the gastrointestinal tract includes the esophagus, stomach, small intestine, large intestine, rectum, and anus, all areas that the ingested gluten would traverse in digestion. The incidence of gastrointestinal cancer can be partially reduced or eliminated if a patient removes gluten from their diet. Additionally, coeliac disease

14157-631: The symptomatology. Symptoms that are commonly associated with autoimmune diseases include: Specific autoimmune diseases have a wide range of other symptoms, with examples including dry mouth, dry eyes, tingling and numbness in parts of the body, unexpected weight loss or gain, and diarrhoea. These symptoms often reflect the body's systemic inflammatory response. However, their occurrence and intensity can fluctuate over time, leading to periods of heightened disease activity, referred to as flare-ups, and periods of relative inactivity, known as remissions. The specific presentation of symptoms largely depends on

14278-414: The thymus, an organ responsible for the maturation of T cells. This process serves as a key line of defense against autoimmunity. If these protective mechanisms fail, a pool of self-reactive cells can become functional within the immune system, contributing to the development of autoimmune diseases. Some infectious agents, like Campylobacter jejuni , bear antigens that resemble, but are not identical to,

14399-400: The thyroid gland (in diseases like Hashimoto's thyroiditis and Graves' disease) and the pancreas (in type 1 diabetes). The impacts of these diseases can range from localized damage to certain tissues, alteration in organ growth and function, to more systemic effects when multiple tissues throughout the body are affected. The appearance of these signs and symptoms can not only provide clues for

14520-405: The transient nature of many symptoms. Treatment modalities for autoimmune diseases vary based on the type of disease and its severity. Therapeutic approaches primarily aim to manage symptoms, reduce immune system activity, and maintain the body's ability to fight diseases. Nonsteroidal anti-inflammatory drugs (NSAIDs) and immunosuppressants are commonly used to reduce inflammation and control

14641-414: The wide range of diseases within this category and their often overlapping symptoms. Accurate diagnosis is crucial for determining appropriate treatment strategies. Generally, the diagnostic process involves a combination of medical history evaluation, physical examination , laboratory tests , and, in some cases, imaging or biopsies . The first step in diagnosing autoimmune disorders typically involves

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