Dopamine Agonists Research Articles

Does Delaying Levodopa Prevent Motor Complications in Parkinson's Disease? A Meta-Analysis.

There has been a long debate whether delaying treatment with levodopa prevents motor complications in Parkinson's disease (PD). We performed a meta-analysis on randomized clinical trials (RCTs) that compared early- versus delayed-start treatment with levodopa in PD. A systematic review was conducted in PubMed, EMBASE, and Web of Science databases from inception to July 1, 2023. Only RCTs that compared early and delayed levodopa treatment in PD were included. Non-randomized comparisons from follow-up studies were included as well. Our primary outcomes were occurrence of overall motor complications, motor fluctuations, and dyskinesias. Seven studies with a total of 1149 patients (636 in the early-start group and 513 in the delayed-start) were included in our analysis. There was no difference between groups regarding motor complications (OR 1.39; 95% CI: 0.68-1.72; P = 0.37) or dyskinesias (OR 1.52; 95% CI: 0.90-2.57; P = 0.11). Motor fluctuations occurred less frequently in the early-start group (OR 0.70; 95% CI: 0.52-0.95; P = 0.02). Nonetheless, on subgroup analysis of dopamine agonists, rate of dyskinesias was smaller in the delayed-start group (OR 1.82; 95% CI: 1.08-3.07; P = 0.03). Delaying treatment with levodopa does not seem to prevent levodopa-related motor complications in PD. Adjunct treatment with dopamine agonists may reduce the need for higher doses of levodopa and thus reduce the risk for dyskinesias but this practice is often associated with a higher frequency of adverse effects related to dopamine agonists.

Accelerated solvent extraction of apomorphine from Nymphaea caerulea (Blue Water Lily) products: A proof‐of‐concept Green extraction for plant materials

AbstractNymphaea caerulea (Blue water lily) is an esthetically pleasing aquatic plant which is widely located across India and Africa. The blue water lily contains an alkaloid called apomorphine which is said to be a sedative, and a nonselective dopamine agonist and is now available in the local and online market in the form of powders and oils for various applications such as sleeping aid, anxiety reliever and sexual performance enhancer. These properties are abused by the consumption of Nymphaea caerulea to achieve a state of “high” which has led the categorization of the same as a novel psychoactive substance. In this paper, a rapid mass spectral analysis was performed for the preliminary screening of commercially available blue water lily products using the Waters Radian as soon as possible instrument, followed by the high performance liquid chromatography‐photo diode array method development and validation of the samples for the qualitative and quantitative analysis of apomorphine. Accelerated solvent extraction as a green alternative to the conventional soxhlet extraction was used in the extraction of the plant material. The method was finally screened for its greenness using the Complex green analytical procedure index method. The method was validated with a linearity of 0.9973; limit of detection and limit of quantitation of 0.02 and 0.18 µg/mL, respectively. The method was able to detect and quantitate apomorphine in two samples from the commercially available natural products of Nymphaea caerulea.

The effect of dysautonomia on motor, behavioral and cognitive fluctuations in Parkinson's disease.

Motor and non-motor fluctuations adversely impact quality of life in Parkinson's disease (PD). Dysautonomia, a feature frequently associated with PD and a possible adverse effect of dopaminergic therapy, may be comorbid with fluctuations. We sought to evaluate the effect of dysautonomia on motor and non-motor fluctuations in PD. Two hundred subjects with PD were evaluated in both "on" and "off" dopamine states to assess changes in symptoms related to dopaminergic fluctuations. Multivariable logistic regression was performed to assess the association of dysautonomia with motor, cognitive, and psychiatric worsening from ON to OFF states with adjustment for disease duration, levodopa equivalent daily dosage (LEDD), and dopamine agonist LEDD. Subjects with dysautonomia had greater odds of clinically meaningful change in motor features (OR 3.0), cognition (OR 3.4) and anxiety (OR 4.3) compared to those without dysautonomia. Dysautonomia may be a contributory mechanism behind fluctuations in PD. The exact nature of this relationship deserves further evaluation.

Mild/moderate phenotypes in AADC deficiency: Focus on the aromatic amino acid decarboxylase protein.

AADC deficiency is a severe neurometabolic inherited rare disorder due to the absence or decrease of dopamine and serotonin levels, causing deep motor and neurodevelopmental impairments. The disease is often fatal in the first decade of life, and pharmacological treatments (dopamine agonists, pyridoxine, and monoamine oxidase inhibitors as the first-line choices) can only alleviate the symptoms. Gene therapy surgery is now available for severe patients in the European Union and the United Kingdom, and follow-up data witness encouraging improvements. In the past few years, mostly due to the increased awareness and knowledge of AADC deficiency, together with newborn screening programs and advancements in methods for genetic diagnosis, the number of mild/moderate phenotypes of AADC deficiency patients has increased to 12% of the total. A review of the genotypes (homozygous/compound heterozygous) of AADC deficiency mild/moderate patients is presented here. The pathogenicity classification of each genetic variant is discussed. Then, we focused on the type of AADC protein possessed by patients and on the predictable structural score of the homodimeric/heterodimeric species of each protein variant. Since the terminology used for genetic and protein variants is the same, we highlighted how it could be misleading. We analyzed the loss-of-function as a fold-change decrease of activity of the recombinant purified AADC enzyme(s) theoretically synthesized by mild/moderate patients. A minimal residual kcat of 8% and/or kcat/Km of 1% seems necessary to avoid a severe disease manifestation. Overall, this cluster of mild/moderate patients needs consideration for a more appropriate and aimed therapeutic approach.

Recovery from hypogonadism in men with prolactinoma treated with dopamine agonists.

In men with prolactinoma treated with dopamine agonists (DA), the extent, timeline, and predictive factors of gonadotropic axis recovery are still unclear. We analyzed data of 97 men with a prolactinoma treated with DA (77/97 macroprolactinomas). We excluded patients with primary hypogonadism, surgery < 12 months after DA initiation, and patients with tumors < 5mm or prolactin < 45µg/l at diagnosis. Among the 97 patients, 12 had normal total testosterone (NT group) and 85 had low testosterone at diagnosis (LT group). In the NT group, testosterone rose from a mean of 13.5 nmol/l to 17.1nmol/l at 6 months (n = 11; p < 0.05) then remained stable at 12 months (n = 8). In the LT group, testosterone rose from a mean of 5.2 nmol/l to 9.6 nmol/l at 6 months (n = 66; p < 0.001) and further to 13.1nmol/l at 12 months (n = 40; p < 0.001) then remained stable. Recovery from hypogonadism occurred in 43%, 50%, and 54% of patients at 6, 12 and 24 months, respectively (61%, 69 and 69% if prolactin was normal). Factors independently associated with persistent hypogonadism at 12 months were at baseline the presence of visual field deficit and lower testosterone levels, while the most significant independent predictor of persistent hypogonadism at one year was a testosterone level < 7.4 nmol/l at 6 months, with 91% sensitivity and 94% specificity. Testosterone levels recover in a small majority of men with prolactinoma mostly during the first year of DA treatment. However, testosterone replacement could be considered earlier in patients with large and compressive tumors, and in whom testosterone remains below 7.4 nmol/l after 6 months of DA treatment.

Sex-based disparities in dopamine agonist response in patients with restless legs syndrome.

This study aimed to investigate sex-related differences in the response to ropinirole and pramipexole in patients with restless legs syndrome (RLS). By analysing clinical parameters and polysomnographic (PSG) findings, we sought to elucidate the potential factors related to sex disparities modulating treatment responses and sleep quality in RLS. A total of 41 drug-free patients with RLS, aged ≥18 years, underwent two consecutive nocturnal PSG recordings, without medication at baseline; before the second night, 26 patients received an oral dose of 0.25 mg pramipexole whereas 15 received 0.5 mg ropinirole. After each PSG recording, patients self-evaluated the severity of their previous night symptoms by means of an ad hoc visual analogue scale (VAS). At baseline, sleep efficiency and percentage of Stage N2 tended to be higher in females while wakefulness after sleep onset was significantly higher in males. After treatment, total leg movements during sleep (LMS), periodic LMS (PLMS), and periodicity indexes were significantly lower in females than in males. The VAS score was lower after treatment in all patients, without differences between the two sexes. This study demonstrates a higher acute responsiveness of PLMS to dopamine agonists (pramipexole and ropinirole) in females than in males with RLS. These findings might be explained by differential sex-related expression of dopamine receptors, especially D3, within the central nervous system. In addition, our findings provide translational hints toward a better tailored and sex-specific approach to the treatment of RLS associated with PLMS, with dopamine agonist possibly associated with a better outcome in females than in males.

Machine Learning-Driven Evaluation of Pramipexole and Mood Stabilizer Combination Therapy in Bipolar Disorder

Background Bipolar disorder (BD) requires long-term management to prevent relapse of depressive episodes. The use of pramipexole, a dopamine agonist, in combination with mood stabilizers has been explored for its potential to prevent antidepressant relapse. Objective This case series aims to evaluate the efficacy and safety of pramipexole in combination with mood stabilizers in preventing antidepressant relapse in patients with bipolar disorder. Methods Two patients with bipolar disorder who were at high risk of relapse after discontinuation of antidepressants were treated with pramipexole in combination with mood stabilizers. Clinical assessments were conducted using the Mood Disorder Questionnaire (MDQ), Clinical Global Impression-Severity (CGI-S), Hamilton Depression Rating Scale (HDRS), and Global Assessment of Functioning (GAF) before and after the addition of pramipexole. Results The combination therapy of pramipexole and mood stabilizers effectively prevented relapse in both patients. MDQ scores decreased, CGI-S scores improved, HDRS scores reduced, and GAF scores increased, with no significant adverse effects reported over a follow-up period of 12 months. Conclusion Pramipexole in combination with mood stabilizers appears to be an effective and safe strategy for preventing antidepressant relapse in patients with bipolar disorder. These findings suggest that this combination therapy could be considered for patients at high risk of relapse after antidepressant discontinuation.

The activation of D2-like dopamine receptors increases NMDA currents in the dorsal raphe serotonergic neurons

The dorsal raphe nucleus (DRN) receives dopaminergic inputs from the ventral tegmental area (VTA). Also, the DRN contains a small population of cells that express dopamine (DRNDA neurons). However, the physiological role of dopamine (DA) in the DRN and its interaction with serotonergic (5-HT) neurons is poorly understood. Several works have reported moderate levels of D1, D2, and D3 DA receptors in the DRN. Furthermore, it was found that the activation of D2 receptors increased the firing of putative 5-HT neurons. Other studies have reported that D1 and D2 dopamine receptors can interact with glutamate NMDA receptors, modulating the excitability of different cell types. In the present work, we used immunocytochemical techniques to determine the kind of DA receptors in the DRN. Additionally, we performed electrophysiological experiments in brainstem slices to study the effect of DA agonists on NMDA-elicited currents recorded from identified 5-HT DRN neurons. We found that D2 and D3 but not D1 receptors are present in this nucleus. Also, we demonstrated that the activation of D2-like receptors increases NMDA-elicited currents in 5-HT neurons through a mechanism involving phospholipase C (PLC) and protein kinase C (PKC) enzymes. Possible physiological implications related to the sleep-wake cycle are discussed.

Risk of Suicidal Ideation and Behavior Following Early-Onset Idiopathic Restless Legs Syndrome Treatment.

To estimate incidence rates of suicidal ideation and behavior following treatment initiation with gabapentinoids or dopamine agonists (DAs) in patients with newly diagnosed early-onset idiopathic restless legs syndrome (RLS) and to examine suicidal behavior risk, comparing between those receiving gabapentinoids and DAs. A new user retrospective cohort study using MarketScan claims data from 2012 to 2019 was conducted. Exposures were monotherapy gabapentinoids or DAs initiated within 60 days of new RLS diagnosis. Three varying outcome measures of suicidality were examined and incidence rates were calculated for each. A log-binomial regression model the estimated relative risk (RR) of the outcomes with gabapentinoids. Propensity score weighting adjusted for baseline covariates, including age, substance use disorders, hyperlipidemia, antipsychotic use, hypnotic/sedative use, and mood stabilizer use, which were most imbalanced before weighting. The cohort included 6672 patients, with 4986 (74.7%) initiating a DA and 1686 (25.3%) initiating a gabapentinoid. Incidence rates for all outcome measures were higher in the gabapentinoid group (suicidality: 21.6 vs. 10.7 per 1000 person-years; suicidality with self-harm: 23.0 vs. 11.1 per 1000 person-years; overdose- and suicide-related events: 30.0 vs. 15.5 person-years). Associated risk of suicidality (adjusted RR, 1.27 [95% CI, 0.86-1.88]); suicidality with self-harm (adjusted RR, 1.30 [95% CI, 0.89-1.90]); or overdose- and suicide-related events (adjusted RR, 1.30 [95% CI, 0.93-1.80]) was not significant with gabapentinoids. Incidence rates for suicidal ideation and behavior were higher among the gabapentinoid group, although increased risk was not detected after adjustment. A possible signal cannot be ruled out given limitations of the data and rarity of the outcome.

Preoperative treatment with dopamine agonist therapy influences surgical outcome in prolactinoma: a retrospective single-center on 159 patients

IntroductionProlactinoma account to the most common pituitary adenomas and current therapy regime constitutes of dopamine agonist therapy (DA) and surgery in selected cases [17]. Due to tumor fibrosis induced by previous DA therapy, surgical removal can be challenging though. Therefore, this study investigates how preoperative DA usage influences perioperative treatment and surgical outcome in prolactinoma and aims to ascertain whether a specific subgroup of prolactinoma patients could derive greater benefit from exclusive surgical intervention.MethodsWe retrospectively analyzed n = 159 surgically treated and histologically confirmed prolactinomas in the sella region from 2013–2022 in our institution. Clinical, radiological and surgical features were analyzed. Univariate and multivariate analyses were performed.ResultsOut of total of 159 prolactinoma patients, 83.6% received previous treatment with DA followed by surgery, while only 16.4% received exclusive surgery. Both groups presented similar initial tumor volumes (1.9cm3 vs. 1.5cm3, p = 0.59) and equal preoperative prolactin levels (PRL) (199.7 µg/l vs. 191.0 µg/l, p = 0.44). Surgical procedures took significantly longer when patients received prior DA treatment (79 min. vs. 70 min., p = 0.0479). Six months after surgery, pretreated patients revealed significantly higher PRL compared to non-treated (107 g/l vs. 8.64 µg/, p = 0.0009). Additionally, untreated microprolactinoma presented a remission of 100%, whereas pretreated exhibited a remission rate of 88.75%.ConclusionThe current study demonstrates that prior DA treatment is associated with significantly longer surgeries, higher recurrence rates and lower rates of normalization of PRL levels after surgery, particularly in microprolactinomas and support the latest recommendations of the Pituitary Society's Consensus Statement 2023, which favors the option of surgery alone as first-line therapy for microprolactinomas.

The Role of Endoscopic Transsphenoidal Surgery in Microprolactinomas: A Retrospective Study

Most patients with microprolactinomas have to take dopamine agonist for a lifetime. Many of them in our center have consulted endoscopic transsphenoidal surgery as an alternative therapy. The current study is a retrospective cohort analysis of 42 patients with microprolactinoma underwent endoscopic transsphenoidal surgery between January 2010 and December 2023 by experienced neurosurgeons in our center. The mean follow-up duration was 30.17 months (range, 13.00-45.40). The short-term (postoperative day 1) remission rate was 95.24% and the long-term (over 1-year follow-up) remission rate was 92.86%. As to remission, the pattern of prolactin level changes on postoperative day 1 was significantly associated with recurrence. In hypoprolactinemia group, all 29 patients showed remission at the 1-year follow-up. In patients with normal PRL levels, 10 out of 11 patients showed remission, while 1 out of 11 patients showed recurrence at the 1-year follow-up. In hyperprolactinemia group, all 2 patients showed recurrence at the 1-year follow-up. Moreover, adenoma location was significantly associated with recurrence as well. In the recurrent group (3 patients), 2 patients belonged to the uncertain group, while the other patient belonged to the lateral group. The surgical complications were temporary and resolved shortly after surgery. According to our findings, endoscopic transsphenoidal surgery performed on patients with microprolactinomas at advanced pituitary tumor centers could be an option with high success rates and low complications. Moreover, improving MRI imaging techniques and/or multidisciplinary team discussion before surgery for microprolactinoma could improve tumor remission after surgery.

Non-Ergot Dopamine Agonists and the Risk of Heart Failure and Other Adverse Cardiovascular Reactions in Parkinson's Disease.

Reports suggest possible risks of adverse cardiovascular reactions, including heart failure, associated with non-ergot dopamine agonist (DA) use in Parkinson's disease (PD). The objectives of our review were to evaluate the risk of heart failure and other adverse cardiovascular reactions in PD patients who received a non-ergot DA compared with other anti-PD pharmacological interventions, placebo, or no intervention. Studies were identified via searches of six bibliographic databases. Randomized controlled trials (RCTs) and non-randomized studies (NRS) were eligible for study inclusion. Random-effect meta-analyses were performed to estimate adverse cardiovascular reaction risks. Quality of evidence was assessed using GRADE. In total, forty-four studies (thirty-six RCTs and eight NRS) satisfied our inclusion criteria. A single RCT found no significant difference in the risk of heart failure with ropinirole compared with bromocriptine (odds ratio (OR) 0.39, 95% confidence interval (CI) 0.07 to 2.04; low certainty). Conversely, three case-control studies reported a risk of heart failure with non-ergot DA treatment. The quality of evidence for the risk of heart failure was judged as low or very low. Findings suggest that non-ergot DA use may be associated with adverse cardiovascular outcomes, including heart failure. Studies are needed to better understand cardiovascular risks associated with PD treatment.

Investigating the Neuroprotective Effect of Withaferin-A in a Parkinsonian Mouse Model

Parkinson's disease (PD) is an enduring and advancing neurodegenerative disorder that impacts millions worldwide. While options to manage its symptoms are available, a definitive cure remains elusive. To enhance the quality of life for PD patients and to alleviate symptoms, various classes of medications are employed including Levodopa (L-Dopa), Dopamine Agonists and Dopamine Agonists. Within this investigation, we investigated the neuroprotective potential of Withaferin-A within a mouse model of Parkinsonism, utilizing a proteomics methodology. Withaferin A, a natural compound extracted from the plant Withania somnifera, colloquially known as ashwagandha, has been explored for its therapeutic attributes across several conditions including PD. To assess the neuroprotective capacity of Withaferin A (WA), we employed a quantitative proteomics strategy to pinpoint proteins with distinct expression patterns in mouse models of Parkinson's disease (PD) treated with WA and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The experimental setup encompassed four groups of mice: Group I as control, group II administered MPTP, group III treated with Withaferin A and group IV receiving Withaferin A treatment. After humane termination and intracardial infusion, the substantia nigra (SN) region of the mice brains was collected. Employing tandem mass tags, quantitative proteomics was executed on the obtained brain samples through an Orbitrap Fusion Mass spectrometer (MS). The subsequent analysis of LC-MS/MS data was conducted via Proteome Discoverer and NCBI's mouse protein database using the MASCOT search engine. This comprehensive exploration unveiled a list of 6044 proteins among which alpha-synuclein was identified. Notably, 133 proteins exhibited differential expression. These differentially expressed proteins played pivotal roles in significant biological processes including cellular processes (signal transduction), metabolic processes (NADP metabolic process) and signaling (dopamine receptor signaling). Crucial pathways uncovered encompass Parkinson's disease and the dopamine receptor-mediated signaling pathway. It is our belief that the insights gleaned from this study provide a foundation for formulating targeted treatment strategies to combat Parkinson's disease, thus potentially enhancing the therapeutic landscape for individuals affected by this condition.

Characteristics and outcomes of men with erectile dysfunction as the presenting symptom due to a lactotroph adenoma

PurposeErectile dysfunction (ED) is frequently underreported in men suffering from prolactinomas and can be challenging to manage. Both dopamine agonists (DAs) and transsphenoidal surgery (TSS) correct hyperprolactinemia and restore gonadal function. However, there is scarce data regarding their effectiveness in correcting ED over the long term.MethodsThis study is a retrospective single-center comparative cohort study analyzing men diagnosed with prolactinomas, both with and without confirmed erectile dysfunction (ED) at diagnosis. Independent risk factors for persistent ED over the long term were examined using multivariate logistic regression.ResultsAmong the 39 men with lactotroph adenomas, ED was one of the presenting symptoms in 22 (56%). The mean age at diagnosis was 45 ± 12 years. Surgery was the primary treatment in 6 (27%) ED patients and 8 (47%) non-ED patients. After a mean follow-up of 74 ± 48 months, remission from hyperprolactinemia was achieved in the majority (76%) of men: 71% in the non-ED cohort and 81% in the ED group (p = 0.70), regardless of the primary treatment strategy (surgical 84% versus medical 72%, p = 0.46). Long-term remission of ED was noted in 16 (73%) patients. Interestingly, high baseline BMI levels emerged as potential risk factors for persistent ED over the long term (OR 1.4, 95%CI 1.0–1.9; p = 0.04), while neither the initial adenoma size nor the primary treatment strategy (i.e., TSS vs. DAs) reached statistical significance.ConclusionsCorrecting hyperprolactinemia and its associated hypogonadism significantly improves ED in the majority of men with prolactinomas over the long term, regardless of the primary treatment strategy employed. In addition to addressing endocrine deficiencies, the early initiation of weight control programs may be considered for men with lactotroph adenomas and ED. Although our study suggests an association between BMI and the risk of persistent ED, further research is needed to establish any causal relationships.

Precision Dopaminergic Treatment in a Cohort of Parkinson's Disease Patients Carrying Autosomal Recessive Gene Variants: Clinical Cohort Data and a Mini Review.

Parkinson's disease (PD) patients harboring recessive gene variants exhibit a distinct clinical phenotype with an early disease onset and relatively mild symptoms. Data concerning individualized therapy for autosomal recessive PD forms are still scarce. Demographic and treatment data of a cohort of PD carriers of recessive genes (nine homozygous or compound heterozygous PRKN carriers, four heterozygous PRKN carriers, and three biallelic PINK1 carriers) were evaluated. The average levodopa equivalent daily dose (LEDD) was 806.8 ± 453.5 (range 152-1810) in PRKN carriers and 765 ± 96.6 (range 660-850) in PINK1 carriers. The majority responded to low/moderate doses of levodopa. The response to dopamine agonists (DAs) was often favorable both as initial and longitudinal therapy. In total, 8/13 PRKN and 1/3 PINK1 carriers were treated with amantadine successfully, and this also applied to patients who could not tolerate levodopa or DAs. In the era of personalized treatment, the therapeutic approach in recessive PD gene carriers might differ as compared to idiopathic PD. Lower LEDD doses were efficient even in patients with a very long disease duration, while a few patients were doing well without any levodopa treatment decades after disease initiation. DAs or amantadine could be used as a first and main line treatment regimen if well tolerated. Literature data on therapeutic strategies in carriers of pathogenic mutations in recessive PD genes, including device-aided treatments, will be further discussed.

Impulse control disorders in Parkinson’s disease: a national Swedish registry study on high-risk treatments and vulnerable patient groups

BackgroundImpulse control disorders (ICDs) are known psychiatric conditions in Parkinson’s disease (PD), especially as a side effect of antiparkinsonian therapy. Screening for vulnerable patients and avoiding high-risk treatments can be...

Cardiometabolic effects of hypoprolactinemia.

The fall of PRL levels below the lower limit of the normal range configures the condition of hypoprolactinemia. Unlike PRL excess, whose clinical features and treatments are well established, hypoprolactinemia has been only recently described as a morbid entity requiring prompt identification and proper therapeutic approach. Particularly, hypoprolactinemia has been reported to be associated with the development of metabolic syndrome and impaired cardiometabolic health, as visceral obesity, insulin-resistance, diabetes mellitus, dyslipidaemia, chronic inflammation, and sexual dysfunction have been found more prevalent in patients with hypoprolactinemia as compared to those with normoprolactinemia. This evidence has been collected mainly in patients on chronic treatment with dopamine agonists for PRL excess due to a PRL-secreting pituitary tumour, and less frequently in those receiving the atypical antipsychotic aripiprazole. Nowadays, hypoprolactinemia appears to represent a novel and unexpected risk factor for cardiovascular diseases, as is the case for hyperprolactinemia. Nevertheless, current knowledge still lacks an accurate biochemical definition of hypoprolactinemia, since no clear PRL threshold has been established to rule in the diagnosis of PRL deficiency enabling early identification of those individual subjects with increased cardiovascular risk directly ascribable to the hormonal imbalance. The current review article focuses on the effects of hypoprolactinemia on the modulation of body weight, gluco-insulinemic and lipid profile, and provides latest knowledge about potential cardiovascular outcomes of hypoprolactinemia.

Parkinson’s disease: Causes, Symptoms, Diagnosis, and Treatment

Parkinson's disease is caused by degeneration of dopamine-producing neurons. Common muscular symptoms include resting tremors, bradykinesia (slowness of movement), muscle rigidity, and postural instability, which can impact a person's ability to move and perform daily activities. Parkinson’s disease is typically diagnosed in mid to late adulthood, with an average age of onset around sixty years, although early-onset cases can occur before the age of fifty. While there is no cure for Parkinson’s disease, medications such as levodopa and dopamine agonists are prescribed to manage symptoms. Deep brain stimulation surgery may be considered in advanced cases of Parkinson's disease.

Diagnostics and treatment of impulse control disorders, psychosis and delirium: systemic review-based recommendations- guideline "Parkinson's disease" of the German Society of Neurology.

Impulse control disorders (ICD), psychosis and delirium are part of the spectrum of behavioural changes associated with Parkinson's disease (PD). The diagnostic and therapeutic management of these rather complex neuropsychiatric conditions has been updated in the clinical guideline by the German Society of Neurology (DGN). Recommendations are based on a systematic literature reviews, other relevant guidelines and expert opinion. Patients receiving dopamine agonists (DA) therapy should be informed about the symptoms and risks of an ICD and should be routinely screened for ICD symptoms. In the presence of an ICD, DA should be reduced or discontinued and psychotherapeutic treatment may be considered. Non-oral therapies (levodopa/carbidopa intestinal gel infusion or deep brain stimulation) may also be an option for appropriate candidates. Psychosis in PD often has a gradual onset. Cognitive and affective disorders, psychiatric and medical comorbidities as well as polypharmacy are risk factors for a psychosis. Non-pharmacological treatments should be implemented as soon as possible and anti-parkinsonian medications should be adjusted/reduced if feasible. For psychosis associated with PD, quetiapine or clozapine should be used on an as-needed basis and for as short a time as is necessary, with safety monitoring. Delirium in PD may be underdiagnosed due to an overlap with chronic neuropsychiatric features of PD. Although transient by definition, delirium in PD can lead to permanent cognitive decline, motor impairment and increased mortality. Management of delirium includes pharmacological and non-pharmacological interventions. The updated guideline encompasses the evidence-based diagnostic, non-pharmacological and pharmacological management of ICD, psychosis and delirium in PD.

Pathogenesis, diagnosis and current treatment of prolactinoma: a review of the literature

ABSTRACT: Prolactinoma is a benign tumor of the pituitary gland that leads to the overproduction of prolactin. It is the most common type of pituitary adenoma, accounting for approximately 50% of all pituitary tumors. The clinical presentation of prolactinoma varies depending on the level of prolactin elevation and the size of the tumor. In women, common symptoms include galactorrhea, amenorrhea, and infertility. Men may present with hypogonadism, decreased libido, erectile dysfunction, and gynecomastia. Large prolactinomas, known as macroadenomas, can cause mass effects such as headaches, visual disturbances due to compression of the optic chiasm, and hypopituitarism due to pressure on surrounding pituitary tissue. Understanding the pathogenesis of prolactinoma is crucial for developing effective treatments and improving patient outcomes. The development of prolactinomas involves a complex interplay of genetic, hormonal, and cellular factors. Treatment of prolactinoma aims to normalize prolactin levels, reduce tumor size, and alleviate symptoms. The first-line therapy is dopamine agonists, such as cabergoline and bromocriptine, with surgery and radiotherapy reserved for refractory cases. Furthermore, chemotherapeutic agent - temozolomide may be a treatment of choice in aggressive or malignant prolactinomas. By understanding the underlying mechanisms and different treatment methods, healthcare providers can optimize the management and outcomes for patients with prolactinoma.