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In medicine, a prodrome is an early sign or symptom (or set of signs and symptoms, referred to as prodromal symptoms[1]) that often indicates the onset of a disease before more diagnostically specific signs and symptoms develop. More specifically, it refers to the period between the first recognition of a disease's symptom until it reaches its more severe form.[1] It is derived from the Greek word prodromos, meaning "running before".[2] Prodromes may be non-specific symptoms or, in a few instances, may clearly indicate a particular disease, such as the prodromal migraine aura.

For example, fever, malaise, headache and lack of appetite frequently occur in the prodrome of many infective disorders. A prodrome can be the early precursor to an episode of a chronic neurological disorder such as a migraine headache or an epileptic seizure, where prodrome symptoms may include euphoria or other changes in mood, insomnia, abdominal sensations, disorientation, aphasia, or photosensitivity. Such a prodrome occurs on a scale of days to an hour before the episode, where an aura occurs more immediate to it.[3]

Prodromal labour, mistakenly called "false labour," refers to the early signs before labour starts.[4]

In mental health

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The prodrome is a period during which an individual experiences some symptoms and/or a change in functioning, which can signal the impending onset of a mental health disorder.[5] It is otherwise known as the prodromal phase when referring to the subsyndromal stage or the early abnormalities in behavior, mood, and/or cognition before illness onset.[6] Early detection of the prodrome can create an opportunity to administer appropriate early interventions quickly to try to delay or decrease the intensity of subsequent symptoms.[7]

Schizophrenia

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See also: Schizophrenia § Onset

Schizophrenia was the first disorder for which a prodromal stage was described.[8] People who go on to develop schizophrenia commonly experience non-specific negative symptoms such as depression, anxiety, and social isolation.[8] This is often followed by the emergence of attenuated positive symptoms such as problems with communication, perception, and unusual thoughts that do not rise to the level of psychosis.[8] Closer to the onset of psychosis, people often exhibit more serious symptoms like pre-delusional unusual thoughts, pre-hallucinatory perceptual abnormalities or pre-thought disordered speech disturbances.[8] As positive symptoms become more severe, in combination with negative symptoms that may have begun earlier, the individual may meet the diagnostic criteria for schizophrenia.[9] Although a majority of individuals who experience some of the symptoms of schizophrenia will never meet full diagnostic criteria, approximately 20–40% will eventually be diagnosed with schizophrenia.[10] One of the challenges of identifying and treating the prodrome is that it is difficult to predict who, among those with symptoms, are likely to meet full criteria later.[citation needed][11]

Duration

[edit]

The prodromal phase in schizophrenia can last anywhere from several weeks to several years, and comorbid disorders, such as major depressive disorder, are common during this period.[12]

Identification/assessments

[edit]

Screening instruments include the Scale of Prodromal Symptoms[13][14] and the PROD-screen.[15][16]

Signs and symptoms of the prodrome to schizophrenia can be assessed more fully using structured interviews. For example, the Structured Interview for Prodromal Syndromes,[17][14] and the Comprehensive Assessment of At Risk Mental States (CAARMS)[18] are both valid and reliable methods for identifying individuals likely experiencing the prodrome to schizophrenia or related psychotic-spectrum disorders.

There are ongoing research efforts to develop tools for early detection of at-risk individuals. This includes development of risk calculators[19] and methods for large-scale population screening.[20]

Interventions

[edit]

Describing the schizophrenia prodrome has been useful in promoting early intervention. Although not all people who are experiencing symptoms consistent with the prodrome will develop schizophrenia, randomized controlled trials suggest that intervening with medication and/or psychotherapy can improve outcomes.[10] Interventions with evidence of efficacy include antipsychotic and antidepressant medications, which can delay conversion to psychosis and improve symptoms, although prolonged exposure to antipsychotics has been associated with adverse effects including tardive dyskinesia, an irreversible neurological motor disorder.[10] Psychotherapy for individuals and families can also improve functioning and symptomatology; specifically cognitive behavioral therapy (CBT) helps improve coping strategies to decrease positive psychosis symptoms.[10] Additionally, omega-3 fish oil supplements may help reduce prodromal symptoms.[10] Current guidelines suggest that individuals who are at "high risk" for developing schizophrenia should be monitored for at least one to two years while receiving psychotherapy and medication, as needed, to treat their symptoms.[21]

Bipolar disorder

[edit]

Symptomology

[edit]

There is also growing evidence that there is a prodromal phase before the onset of bipolar disorder.[22] Although a majority of individuals with bipolar disorder report experiencing some symptoms preceding the full onset of their illness, the prodrome has not yet been described systematically. Descriptive reports of bipolar prodrome symptoms vary and often focus on nonspecific symptoms of psychopathology, making identification of the prodromal phase difficult. The most commonly observed symptoms are too much energy, elated or depressed mood, and alterations in sleep patterns.[23] There are no prospective studies of the prodrome to bipolar disorder, but in the Longitudinal Assessment of Manic Symptoms (LAMS) study, which followed youth with elevated symptoms of mania for ten years,[24] approximately 23% of the sample met the bipolar criteria at the baseline and 13% of which did not meet the criteria at baseline eventually were diagnosed with bipolar disorder.[25]

Duration

[edit]

The reported duration of the prodrome to bipolar disorder varies widely (mean = 27.1 ± 23 months);[23] for most people, evidence suggests that the prodromal phase is likely to be long enough to allow for intervention.[26]

Identification/assessments

[edit]

Symptoms consistent with the prodrome to bipolar disorder can be identified through semi-structured interviews such as The Bipolar Prodrome Symptom Interview and Scale-Prospective (BPSS-P),[27] and the Semi-structured Interview for Mood Swings[28] and symptom checklists like the Young Mania Rating Scale (YMRS)[29] and the Hamilton Depression Scale (HAM-D).[30][23][22]

Interventions

[edit]

Early intervention is associated with better outcomes for people with prodromal symptoms of bipolar disorder. Interventions with some evidence of efficacy include medication (e.g. mood stabilizers, atypical antipsychotics) and psychotherapy. Specifically, family-focused therapy improves emotion regulation and enhances functioning in both adults and adolescents.[31] Interpersonal and Social Rhythm Therapy (IPSRT) may be beneficial for youth at risk of developing the disease by helping to stabilize their sleep and circadian patterns.[32] Psychoeducational Psychotherapy (PEP) may be protective in individuals at risk of developing bipolar disorder and are associated with a four-fold reduction in risk for conversion to bipolar disorder.[33] This research needs to be explored further, however, it is currently thought to produce improvements in decreased stress due to social support and improved functioning through the skills developed in PEP. PEP can prove especially beneficial for individuals presenting transitional mania symptoms as it can assist caregivers in recognizing prodromal mania symptoms and knowing the next steps towards early intervention.[33] The key goals of this type of therapy are to provide education about mood disorders and treatments, social support, and to build skills in symptom management, emotion regulation, and problem-solving and communication. This research is in its infancy, further investigations will be necessary to determine which methods lead to the best outcomes and for whom.[34]

In neurological conditions

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Neurodegenerative diseases

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Several neurodegenerative diseases have a prodromal phase. Early impairments in behavior, personality and language may be detected in Alzheimer's disease.[35] In dementia with Lewy bodies, there is an identifiable set of early signs and symptoms that can appear 15 years or more before dementia develops.[36] The earliest symptoms are constipation and dizziness from autonomic dysfunction, hyposmia (reduced ability to smell), visual hallucinations, and rapid eye movement sleep behavior disorder (RBD).[37] RBD may appear years or decades before other symptoms.[38] In Parkinson's disease the loss of sense of smell may aid in earlier diagnosis.[39] Multiple sclerosis may have a prodromal phase.[40][41]

Migraine

[edit]

The prodromal phase of migraine is not always present, and varies from individual to individual, but can include ocular disturbances such as shimmering lights with reduced vision, altered mood, irritability, depression or euphoria, fatigue, yawning, excessive sleepiness, craving for certain food (e.g. chocolate), stiff muscles (especially in the neck), hot ears, constipation or diarrhea, increased urination, and other visceral symptoms.[42]

See also

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References

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[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Prodrome

View on Grokipedia
from Grokipedia
A prodrome is an early set of nonspecific signs, symptoms, or other findings that occur before the onset of the typical, more characteristic manifestations of a , serving as a warning of its impending development. This phase, derived from word prodromos meaning "forerunner" or "precursor," represents a transitional period that can vary in duration from hours to years depending on the condition. In , the prodrome is recognized across various specialties, particularly in infectious, neurological, and psychiatric disorders, where it enables opportunities for early detection and intervention to potentially mitigate disease progression. For instance, in infectious diseases such as or , prodromal symptoms often include fever, , and , appearing days before the or that define the acute phase. In neurological conditions like migraines, the prodrome may manifest 1–2 days prior to the with subtle changes such as mood swings, cravings, increased , or frequent yawning, affecting up to 60–80% of patients. Similarly, in , a prodrome can involve a vague of impending , including anxiety or irritability, occurring hours to days beforehand. The concept holds particular significance in , where the prodrome of psychotic disorders like involves a gradual emergence of subthreshold symptoms such as social withdrawal, attenuated psychotic experiences (e.g., unusual beliefs or perceptual changes), and declining function, often lasting months to years before full . This phase, sometimes termed the "ultra-high-risk" state, affects 20–40% of individuals who may convert to within 2–4 years, highlighting the value of prodromal identification for preventive treatments like or low-dose antipsychotics to improve long-term outcomes. In neurodegenerative diseases such as , prodromal features—including increased healthcare utilization, cognitive impairments, and fatigue—can precede clinical diagnosis by up to 10–20 years, with recent 2025 research indicating signs up to 15 years prior; this underscores the role of biomarkers like MRI lesions or autoantibodies in early risk stratification. Overall, recognizing the prodrome across these contexts emphasizes its diagnostic and prognostic importance, though challenges remain due to its nonspecific nature, which can overlap with other conditions and complicate timely intervention.

Overview and General Principles

Definition

The term prodrome originates from word prodromos, meaning "running before" or "running forward," signifying symptoms that precede the main phase of a . In , a prodrome is defined as one or more early, often nonspecific signs or symptoms that signal the impending onset of a or illness, before the full clinical manifestation. This phase distinguishes conditions with gradual symptom escalation from those with sudden acute onset or prolonged incubation, allowing for potential early intervention. Prodromal phases occur across various categories; in infectious diseases, for instance, they may present as fever, , , or preceding the characteristic , as seen in . In chronic conditions, prodromes often involve subtle, nonspecific alterations in functioning that foreshadow more overt , though these vary widely by type. The prodrome must be differentiated from related concepts: unlike an , which consists of specific perceptual disturbances (such as visual or sensory changes) occurring immediately before an acute event like a or , the prodrome is typically earlier and less focal. In contrast, the preclinical phase refers to subclinical pathological changes—detectable via biomarkers or imaging but without any noticeable symptoms—preceding the symptomatic prodrome. The prodrome's recognition is especially valuable in fields like and for enabling timely monitoring and management.

Historical Context

The concept of the prodrome, derived from the Greek word meaning "running ahead," originated in ancient as a descriptor for early warning signs preceding the full manifestation of illness. , in his corpus particularly the treatises on epidemics, documented prodromal symptoms such as unusual , sensory changes, and behavioral shifts that foreshadowed outbreaks of diseases like plagues, emphasizing environmental and seasonal precursors to guide clinical observation. During the 18th and 19th centuries, the prodrome gained formal recognition in , notably for . Swiss physician Samuel Tissot's 1778 treatise Traité des nerfs et de leur maladies provided one of the earliest systematic accounts, describing prodromal phases involving , visual auras, and mood alterations hours or days before the onset, drawing on both historical texts and his clinical practice to differentiate from other cephalalgias. This period marked a transition from anecdotal reports to more structured neurological classifications, influencing later 19th-century works that linked prodromes to vascular and disturbances. In early 20th-century , following Sigmund Freud's explorations of and latent psychic processes, the prodrome was adapted to psychotic disorders. Eugen Bleuler's 1911 monograph Dementia Praecox or the Group of formalized the prodromal phase in as a subtle period of affective flattening, thought disorganization, and social withdrawal preceding overt psychotic symptoms, framing it as part of the illness's chronic progression rather than isolated precursors. This conceptualization shifted focus from to recognizing gradual deteriorations, though empirical validation remained limited until mid-century. Key milestones in the mid-to-late advanced prodromal research in . In 1966, John Chapman analyzed subjective experiences in young patients, identifying depersonalization, perceptual anomalies, and volitional disruptions as core early symptoms, based on interviews with 40 cases to highlight their predictive value over Bleuler's primary symptoms. The 1990s brought validation in affective disorders through Maurizio Fava and Robert Kellner's review, which defined bipolar and depressive prodromes as clusters of nonspecific symptoms like sleep changes and anxiety emerging weeks to years before full episodes, advocating their use for preventive strategies in 24 reviewed studies. The witnessed a from retrospective to prospective prodrome identification, particularly in , via ultra-high-risk (UHR) models. Developed by Patrick McGorry and Alison Yung in the mid-1990s at the , these criteria—encompassing attenuated psychosis, brief limited intermittent psychotic symptoms, and genetic risk with deterioration—were prospectively tested in longitudinal cohorts during the , demonstrating 20-40% transition rates to within 2-3 years and enabling early intervention trials. In the and , and have refined prodrome detection across disorders. Functional MRI and diffusion tensor imaging studies of UHR individuals revealed progressive gray matter reductions in frontal and temporal regions preceding onset, with meta-analyses confirming their prognostic utility in distinguishing converters from non-converters. Similarly, research, including elevated and inflammatory markers, has supported earlier identification in neurodegenerative prodromes, integrating multimodal data for improved risk stratification.

Clinical Characteristics

The prodromal phase exhibits a wide range of durations, typically spanning from seconds to years, contingent on the acuity of the underlying ; acute processes such as infections or seizures often feature short prodromes lasting minutes to days, whereas chronic neurodegenerative conditions may involve extended periods of up to several years. Common nonspecific symptoms during this phase include or lack of energy, mood or affective changes, , , sleep disturbances, cognitive impairments such as poor concentration or "fog," and somatic complaints like , , , or . These manifestations are inherently vague and not , often resembling commonplace experiences rather than signaling a specific . Prodromal presentations demonstrate considerable variability, manifesting as subtle, intermittent, or progressively intensifying symptoms that may resolve spontaneously or escalate; this heterogeneity is shaped by individual factors, including age and genetic predispositions, which influence symptom onset, severity, and trajectory. The nonspecific quality of prodromal symptoms presents substantial diagnostic challenges, as they frequently overlap with normal physiological responses to stress, transient emotional states, or unrelated conditions, thereby increasing the risk of false positives in clinical assessments; longitudinal monitoring over time is crucial for discerning true prodromal patterns from benign fluctuations. Early recognition of the prodrome holds prognostic significance, as it facilitates timely interventions that are associated with enhanced clinical outcomes by mitigating progression and improving overall across diverse pathologies.

Prodrome in Psychiatric Disorders

Schizophrenia

The prodromal phase of features a distinct symptom profile, including attenuated positive symptoms such as unusual thought content, suspiciousness, and perceptual disturbances; negative symptoms like social withdrawal, , and emotional blunting; cognitive deficits encompassing and impairments; and a progressive decline in social, academic, or occupational functioning. These symptoms often emerge subtly and intensify over time, distinguishing the prodrome from other psychiatric precursors by their emphasis on subthreshold psychotic-like experiences alongside persistent negative and cognitive features. This phase typically spans 1 to 5 years, commencing in late or early adulthood (ages 15 to 30), with a gradual progression from nonspecific changes to more pronounced psychotic . The duration can vary, but longitudinal studies indicate an average of 2 to 3 years before transition to full , influenced by individual factors such as age at onset and environmental exposures. Recent advances as of 2025 include the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ) program, which explores body fluid biomarkers for identifying risk, enhancing early detection capabilities. Additionally, a 2024 study linked cognitive impairments in psychotic disorders to alterations in brain network organization, offering promise for improved early intervention strategies. Identification of the schizophrenia prodrome relies on standardized assessments like the Structured Interview for Prodromal Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS), which evaluate symptom severity, frequency, and duration. These tools define ultra-high-risk (UHR) states through criteria including genetic risk (e.g., family history of psychosis) plus recent functional deterioration, attenuated psychotic symptoms of at least one week's duration, or brief limited intermittent psychotic symptoms. UHR identification enables early monitoring, with conversion rates to full psychosis estimated at 20% to 40% within 2 to 3 years without intervention. Interventions during this phase prioritize psychosocial approaches, such as for (CBTp) to address attenuated symptoms and coping strategies, alongside family education and support to mitigate stress. Low-dose antipsychotics may be considered for those with significant distress or rapid symptom worsening, though evidence supports their use cautiously due to risks. These strategies aim to delay or prevent transition, with trials demonstrating reduced conversion rates through integrated early intervention programs. Risk factors specific to the schizophrenia prodrome include a family history of psychotic disorders, which elevates genetic vulnerability; use, particularly during , that can accelerate symptom onset; and urban upbringing, associated with increased incidence due to social adversity and environmental stressors. These factors interact with the prodromal process, heightening the likelihood of progression when combined with UHR criteria.

Bipolar Disorder

The prodrome of is characterized by subthreshold hypomanic symptoms such as increased energy, reduced need for , and , alongside depressive features including low mood and , often accompanied by cyclothymic mood instability and nonspecific anxiety or disturbances. These symptoms typically emerge gradually and can be difficult to distinguish from other mood fluctuations, with mood lability and subsyndromal depression being among the most consistent early indicators. In high-risk individuals, such as offspring of parents with , chronic and may also precede full syndromal episodes. The duration of the bipolar prodrome varies, often lasting 1-2 years prior to the first full manic or depressive episode, though some studies report ranges from several months to over 7 years, with prodromes before recurrent episodes typically spanning days to weeks. Onset commonly peaks in late or early adulthood, around ages 15-25, during a period of heightened vulnerability to affective instability. Prodromal phases are frequently triggered by stressors, such as interpersonal conflicts or life transitions, and individuals with a anxiety disorders face an elevated risk of progression to . As of 2025, research has advanced toward transdiagnostic models of the prodrome for severe mood disorders, analyzing temporal relationships between symptoms over 2 years to better predict progression. A 2024 qualitative study further identified key prodromal signs like sleep changes and mood lability in first manic episodes, supporting earlier identification in at-risk individuals. Detection of the bipolar prodrome relies on tools like mood charting to track daily affective changes and the Bipolar Prodrome Symptom Interview and Scale-Prospective (BPSS-P), a semi-structured assessment that evaluates mania, depression, and general symptoms on a 0-6 severity scale, demonstrating strong reliability and validity in distinguishing at-risk youth from controls. Emphasis is placed on family history of mood disorders and documentation of subthreshold episodes, as these factors enhance predictive accuracy in clinical settings. Early interventions for the bipolar prodrome include to foster symptom recognition and adherence, which has been shown to reduce relapse rates and episode severity in at-risk individuals. Mood stabilizers such as provide prophylaxis against manic escalation, with evidence from youth studies indicating decreased depressive symptoms and upon early initiation. Lifestyle measures, including through therapies like Interpersonal and Social Rhythm Therapy, help stabilize circadian rhythms and mitigate prodromal anxiety. Overall, prospective studies confirm that early detection and intervention shorten the duration of untreated illness and improve long-term functional outcomes.

Major Depressive Disorder

The prodromal phase of (MDD) refers to the period preceding a full depressive episode, characterized by a distinct pattern of subclinical symptoms that often build from underlying or subsyndromal states. Common symptoms include , , sleep disturbances such as initial or delayed , anxiety, reduced concentration, and somatic complaints like unexplained aches or tension. These manifestations differ from more general nonspecific and anxiety by their progressive intensification toward core depressive features, such as persistent low mood, without involving mood elevation. A 1990 study of first-episode patients identified generalized anxiety and as particularly prevalent prodromal signs compared to healthy controls, with similar patterns recurring in relapses. The duration of the prodrome in MDD varies widely but is typically present in most cases, lasting from weeks to months before the onset of a full , though it can extend to years in recurrent or high-risk individuals. A 2024 study found that 93.2% of patients reported a prodromal phase with a duration of 7.9 months (SD = 12.5), highlighting its variability across episodes. This phase commonly emerges in adulthood, but it can begin in , particularly among those with early subclinical symptoms, and may persist longer in recurrent cases due to residual effects from prior episodes. Research from a 2018 clinical study reported a prodromal duration of 115 days (range: 20–300 days), emphasizing the need for timely recognition to prevent progression. Recent investigations as of 2025 have examined the duration of untreated illness in MDD, underscoring how delays in treatment initiation during the prodrome affect long-term prognosis. A 2024 study on stressors during the prodromal phase identified interpersonal and environmental triggers as key contributors, informing targeted preventive measures. Identification of the MDD prodrome relies on prospective tracking through validated inventories that monitor emerging symptoms, with a focus on stressors and lingering residual symptoms from previous episodes. Tools such as the Inventory of Depressive Symptomatology (IDS) or its quick version (QIDS) are commonly used for self-report or clinician-rated assessment of symptom severity, enabling early detection of subclinical changes like or issues. The research, including analyses, pinpointed prodromal as a key predictor of impending episodes, often linked to heightened perceived stress from interpersonal or environmental triggers. A 2018 study using the Clinical Interview for Depression and Related Syndromes (CIDRS) confirmed that such assessments help differentiate prodromal signs in remitted patients. Early interventions during the MDD prodrome aim to mitigate progression to full episodes, primarily through psychological approaches like (CBT) and techniques, with antidepressants considered for high-risk cases. CBT has demonstrated efficacy in reducing prodromal symptoms and preventing onset, with meta-analyses showing small-to-moderate effects (Hedges' g = 0.35) in subsyndromal depression across 18 trials, including school-based programs for adolescents. , such as CBT for , addresses common prodromal features like sleep disturbances and has shown moderate-to-large benefits in 23 studies. For individuals at elevated risk, low-dose antidepressants may be initiated alongside therapy, though evidence emphasizes psychotherapy's role in long-term prevention. The prodrome is notably associated with higher perceived stress, such as from family loss or relational conflicts, and is more prevalent in women and those with a family history of depression, where correlates strongly with genetic vulnerability.

Prodrome in Neurological Disorders

Migraine

The prodromal phase of migraine, also known as the premonitory phase, precedes the by a variable period and is characterized by a range of subtle symptoms that signal an impending attack. Common manifestations include mood alterations such as , depression, or , alongside food cravings—often for carbohydrates or sweets—and excessive yawning. and are also frequently reported, reflecting autonomic and musculoskeletal involvement. These symptoms can overlap with general somatic complaints but are distinct in their predictive association with onset. This phase typically lasts from a few hours to 48 hours before the begins, though durations of 1–6 hours are common in many episodes. In individuals with chronic , defined as 15 or more days per month, prodromal symptoms may recur frequently, aligning with the episodic nature of attacks. Cognitive symptoms like "brain fog," manifested as difficulty concentrating or thinking, affect up to 30% of those experiencing prodrome and contribute to impaired daily functioning. Identification of the prodromal phase relies on patient self-reporting through diaries or electronic tools to track symptom patterns and their timing relative to headaches. Recognition often involves noting associations with triggers such as stress, which can exacerbate mood changes, or hormonal fluctuations like withdrawal in women. No standardized diagnostic scales exist specifically for migraine prodrome, but prospective logging enables prediction of attacks with high reliability in about 77% of cases. Management focuses on early intervention to mitigate headache progression, including non-pharmacological measures like rest in a quiet, dark environment, hydration, and consistent sleep schedules to address fatigue and lifestyle triggers. Over-the-counter analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs) can alleviate symptoms like neck stiffness, while lifestyle adjustments—such as avoiding known triggers—reduce recurrence. Pharmacological options include triptans like rizatriptan or gepants such as ubrogepant, which, when administered during prodrome, prevent moderate-to-severe headaches in 45–46% of cases compared to 28–29% with placebo, based on neurology clinical trials. These strategies highlight the prodrome as a critical window for abortive therapy, supported by neuroimaging evidence of early brain activation patterns.

Epilepsy

The prodrome in refers to a phase of subjective symptoms that precede the onset of a by minutes to days, distinct from the aura, which marks the beginning of the ictal phase itself. Common prodromal symptoms include headaches, mood alterations such as and anxiety, , nonspecific "funny feelings," and changes in patterns. These symptoms are reported by 20-50% of patients with , with a mean of approximately 22% across multiple studies, though rates vary by type and individual factors. The duration of the prodromal phase is highly variable, typically ranging from 10 minutes to several days, with most episodes lasting between 30 minutes and 24 hours. In IGE, emerging evidence points to an extended prodromal period detectable up to 5 years before the first , characterized by increased healthcare utilization, including higher rates of prescriptions and medical visits. This long-term pattern underscores the potential for early identification in at-risk individuals, though short-term prodromes are more commonly self-reported in clinical settings. Identification of prodromal symptoms relies primarily on self-reports and seizure diaries, which help track patterns and reliability. (EEG) monitoring can reveal associated preictal patterns, such as subtle abnormalities, though it is not always definitive for prodrome detection. Prodromes are often linked to triggers like , which may exacerbate symptoms and increase seizure risk. Interventions during the prodromal phase focus on leveraging these warnings to mitigate impact, including strategies such as assuming a safe position, timing antiepileptic medication doses, and avoiding high-risk activities. Patient programs emphasize recognition of personal prodromal signs to empower self-management, with evidence showing that intensive self-management can reduce frequency and improve . These approaches highlight the clinical value of prodromes in enhancing patient autonomy and safety, particularly when tied to modifiable triggers.

Neurodegenerative Diseases

The prodromal phase of neurodegenerative diseases represents a prolonged period of subclinical pathological changes preceding overt clinical symptoms, often involving protein misfolding and aggregation known as proteinopathies. In conditions such as (PD), (AD), and (MS), this phase is characterized by early non-motor symptoms that reflect underlying neuronal damage, including olfactory dysfunction, gastrointestinal issues, sleep disturbances, cognitive subtleties, and systemic complaints like fatigue and pain. Recent reviews highlight that these prodromal manifestations stem from preclinical protein accumulation, such as in PD and amyloid-beta/ in AD, occurring years before motor or cognitive decline becomes evident. In PD, common prodromal symptoms include , , and rapid eye movement (REM) sleep behavior disorder, which can manifest as vivid dreaming with physical enactments. These non-motor features often emerge due to early and involvement. For AD, the prodrome frequently presents as (MCI) with subtle memory lapses, such as difficulty recalling recent events, alongside neuropsychiatric symptoms like . In MS, prodromal signs encompass musculoskeletal pain, mood disorders including depression and anxiety, and chronic fatigue, reflecting inflammatory processes in the before demyelinating lesions become clinically apparent. The duration of this prodromal phase varies by disease but typically spans years to decades; for instance, in PD, it can exceed 10 years, with some evidence suggesting up to 20 years of latency. Identification of the prodromal stage relies on biomarker assessments and screening tools to detect early . In PD, dopamine transporter imaging via DaTscan reveals reduced striatal uptake, while prospective cohorts like the Parkinson's Progression Markers Initiative (PPMI) track non-motor symptoms and longitudinally. For , cognitive screens such as the (MoCA) identify MCI, supplemented by cerebrospinal fluid or blood-based amyloid and tau . In MS, clinical of prodromal symptoms like fatigue and mood changes, combined with MRI for subtle changes, aids detection. Early interventions focus on symptomatic management and prevention trials; exercise programs alleviate non-motor symptoms in prodromal PD, such as improving constipation and sleep quality, while disease-modifying therapies are tested in at-risk cohorts. Advanced detection methods include retinal imaging for amyloid deposits in and olfactory tests for in PD, enabling earlier enrollment in neuroprotective trials.

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