Parkinson's Disease

General information

The theme of 2025/26 is Parkinson's disease and levodopa monitoring. Parkinson's disease is a progressive neurodegenerative disorder caused by the loss of dopamine-producing neurons in the substantia nigra region of the brain. This results in a severe dopamine deficiency in the basal ganglia, which are critical for initiating and smoothing movement. The primary motor symptoms advancing from this deficit include tremor, muscle rigidity, slowness of movement, and postural instability.[1] Generally, the management of motor symptoms relies on the administration of levodopa (L-Dopa), a dopamine precursor that can cross the blood-brain barrier, unlike dopamine itself.[2] Levodopa is absorbed from the gastrointestinal tract and transported via the bloodstream to the brain, where it is decarboxylated into dopamine to restore motor function. Consequently, the concentration of levodopa in the blood serum directly influences the therapeutic effect and the onset of motor complications. A standard therapeutic range for plasma levodopa is typically considered to be between 1 - 3 µg/mL (approximately 5 - 15 µmol/L) following a dose.[3] As the disease progresses, the relationship between dose and clinical response becomes unpredictable, leading to motor fluctuations and dyskinesias. Therefore, monitoring levodopa levels serves as a crucial tool for optimizing dosing regimens. There is no cure for Parkinson's disease, although medications and therapies can manage the symptoms. In advanced cases, patients may undergo surgical treatments like deep brain stimulation to help control motor symptoms.[4]

History and Current Situation 0f Parkinson's Disease

Some accounts trace tremor-like syndromes to ancient medical texts: for example, an Ayurvedic treatise (c. 10th century BC) describes a disorder of shaking, loss of movement, and drooling, resembling features of Parkinson’s disease [5]. Later writers such as Sylvius de la Boë (1680) and Sauvages (1768) described rest tremor and gait festination, hinting at the same syndrome [6]. The disease as a defined neurologic entity was first characterized in 1817 by James Parkinson in An Essay on the Shaking Palsy, describing six cases with tremor, rigidity, and progressive motor decline [7]. In 1865 William Sanders proposed the term “Parkinson’s disease,” which was later popularized by Jean-Martin Charcot, who clarified the triad of rigidity, tremor, and bradykinesia [8]. In the late 19th and early 20th centuries, neuropathological studies revealed degeneration of the substantia nigra and related basal ganglia circuits as the anatomical substrate of the disease [9]. Until mid-20th century treatments were limited to anticholinergic agents (e.g. belladonna alkaloids, trihexyphenidyl) and ablative surgeries. The major breakthrough came in the 1960s when dopamine’s role was discovered, and levodopa therapy was introduced, revolutionizing symptomatic treatment [10]. In later decades, neurosurgical techniques such as deep brain stimulation (DBS) became available for patients with advanced symptoms [8,9].

Parkinson’s disease (PD) is now the second most common neurodegenerative disorder, next to Alzheimer’s disease, imposing a rapidly growing global burden [10,11]. According to the Global Burden of Disease (GBD) Study (2021), 11.77 million people worldwide lived with PD, with an age-standardized prevalence of ~138.6 per 100,000 and incidence ~15.6 per 100,000 [11]. From 1990 to 2021, age-standardized prevalence, incidence, DALYs, and mortality all increased substantially across most regions [3,11]. Projections suggest prevalence may rise to ~ 267 cases per 100,000 by 2050, representing ~76 % growth from current levels [8]. Some estimates forecast that the number of PD patients may more than double by 2050 to ~ 25 million globally [12].

Pathologically, PD is characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta and accumulation of α-synuclein aggregates (Lewy bodies) [9,10]. Both genetic predispositions (e.g. LRRK2, GBA mutations) and environmental exposures (e.g. pesticides, industrial chemicals) are believed to contribute, but causality remains uncertain [7,13]. Clinically, the disease manifests with motor symptoms (bradykinesia, rigidity, resting tremor, postural instability) and nonmotor features (e.g. hyposmia, REM sleep behavior disorder, autonomic dysfunction, depression), many of which may precede motor onset [10]. Diagnosis remains primarily clinical, aided by response to dopaminergic therapy; imaging and molecular biomarkers are under investigation but not yet definitive for routine use [9]. Treatment remains symptomatic: levodopa is the gold standard, though long-term use is often complicated by motor fluctuations and dyskinesias; DBS and other neuromodulatory approaches are used in selected patients [10,8]. Major ongoing challenges include disease heterogeneity, lack of validated biomarkers for early detection and progression, and unequal access to advanced diagnostics and therapies globally. Wearable and biosensor technologies are a promising frontier for monitoring PD and detecting early signs.