Deep Brain Stimulation or Duodenal Levodopa/Carbidopa Infusion: Choosing the Right Therapy for Individual Patients

CNS Spectrums ◽  
2008 ◽  
Vol 13 (S7) ◽  
pp. 8-10 ◽  
Author(s):  
Jens Volkmann

Parkinson's disease is a progressive neurodegenerative disorder with prominent motor features. The cardinal motor signs, bradykinesia, rigidity, and tremor, are treated effectively by dopaminergic therapies. Levodopa is standard, and often initial, therapy for patients with this condition. However, with continued treatment, and as the disease progresses, the response to oral dopaminergic drugs becomes unstable and motor fluctuations emerge, including off periods (when medication effects wear off) and dyskinesia (dystonic or choreatic movements) (Slide 1). Risk factors for motor complications include younger age at disease onset, longer disease duration, higher levodopa dosage, and more severe motor symptoms.

Author(s):  
Leslie Wayne Ferguson ◽  
Ali H. Rajput ◽  
Alexander Rajput

AbstractBackground:Several studies have compared early-onset Parkinson disease (EOPD) and late-onset Parkinson disease (LOPD) but most are not based on autopsy confirmed cases.Methods:We compared clinical and pharmacological profiles, time to reach irreversible Hoehn and Yahr (H&Y) Stage 3 and levodopa motor complications in autopsy confirmed EOPD and LOPD cases.Results:At first clinic visit EOPD cases were younger but had longer disease duration and they died at a younger age (all p<0.0001). Anti-Parkinsonian drug use, including levodopa, was significantly delayed in EOPD. Lifetime use of amantadine (p<0.05) and dopamine agonists (p<0.01) were higher in EOPD. While lifetime use of levodopa was similar in the two groups, levodopa was used for a significantly longer period by EOPD (p< 0.0001). EOPD had a higher cumulative incidence of dyskinesias (p<0.01), wearing-off (p<0.01), and on-off (p<0.01). However, the time to dyskinesia onset was similar in the two groups. The threshold to wearing-off was much longer in EOPD (p<0.01). H&Y stage profile at first visit was similar in the two groups. The duration from disease onset to reach irreversible H&Y stage 3 was significantly longer in EOPD.Conclusions:Our observations indicate that progression of PD is slower in EOPD and suggest that the pre-clinical interval in this group is longer. These findings can be used for case selection for drug trials and studies of the pathogenesis of PD.


Author(s):  
Pedro Barbosa ◽  
Atbin Djamshidian ◽  
Andrew John Lees ◽  
Thomas Treharne Warner

ABSTRACT Background: Impulsive compulsive behaviors (ICBs) can affect a significant number of Parkinson’s disease (PD) patients. Objective: We have studied brain samples from a brain bank of PD patients who received apomorphine via continuous infusion in life to assess the prevalence and outcome of ICBs. Methods: A search on the Queen Square Brain Bank (QSBB) database for cases donated from 2005 to 2016 with a pathological diagnosis of idiopathic PD was conducted. Notes of all donors who used apomorphine via continuous infusion for at least three months were reviewed. Clinical and demographic data were collected, as well as detailed information on treatment, prevalence and outcomes of ICBs. Results: 193 PD cases, 124 males and 69 females, with an average age at disease onset of 60.2 years and average disease duration of 17.2 years were reviewed. Dementia occurred in nearly half of the sample, depression in one quarter, and dyskinesias in a little over 40%. The prevalence of ICBs was 14.5%. Twenty-four individuals used apomorphine infusion for more than three months. Patients on apomorphine had younger age at disease onset, longer disease duration, and higher prevalence of dyskinesias. The prevalence of de novo ICB cases among patients on apomorphine was 8.3%. Apomorphine infusion was used for an average of 63.1 months on an average maximum dose of 79.5 mg per day. Ten patients remained on apomorphine until death. Conclusions: Apomorphine can be used as an alternative treatment for patients with previous ICBs as it has low risk of triggering recurrence of ICBs.


2020 ◽  
Author(s):  
Philip C. Buttery ◽  
Roger A. Barker

Abstract Parkinson’s disease (PD) is a neurodegenerative disorder that carries large health and socioeconomic burdens. Current therapies for PD are ultimately inadequate, both in terms of symptom control and in modification of disease progression. Deep brain stimulation and infusion therapies are the current mainstay for treatment of motor complications of advanced disease, but these have very significant drawbacks and offer no element of disease modification. In fact, there are currently no agents that are established to modify the course of the disease in clinical use for PD. Gene and cell therapies for PD are now being trialled in the clinic. These treatments are diverse and may have a range of niches in the management of PD. They hold great promise for improved treatment of symptoms as well as possibly slowing progression of the disease in the right patient group. Here, we review the current state of the art for these therapies and look to future strategies in this fast-moving field.


Lupus ◽  
2021 ◽  
pp. 096120332110124
Author(s):  
Gian Domenico Sebastiani ◽  
Francesca Romana Spinelli ◽  
Elena Bartoloni ◽  
Alessandra Bortoluzzi ◽  
Enrica Bozzolo ◽  
...  

Objective To report baseline data of SLE patients enrolled in the Lupus Italian Registry (LIRE). Methods Patients affected by SLE aged ≥ 16 years were consecutively recruited in a multicenter prospective study comparing two cohorts: patients starting biologic immunosuppressants (BC) and patients starting non-biologic immunosuppresants (NBC). Results 308 patients were enrolled, 179 in NBC and 129 in BC. Mean age at disease onset and at diagnosis was significantly higher in NBC (p = 0.023, p = 0.045, respectively). Disease duration was longer in BC (p = 0.022). Patients in BC presented arthritis more frequently (p = 0.024), those in NBC nephropathy (p = 0.03). Quality of life was worse in BC (p = 0.031). Anti-dsDNA, low C3, were significantly more frequent in BC (p < 0.001, p = 0.009, respectively). Mycophenolate, methotrexate and azathioprine were the drugs more frequently prescribed in NBC, Belimumab and Rituximab in BC. Conclusion The predominant organ involvement was different in the two cohorts: kidney involvement predominated in NBC, joint involvement in BC. Despite the younger age at disease onset, patients of the BC had a longer disease duration and more frequently had taken a cumulative prednisone dosage greater than 10 g. Even the pattern of clinical manifestations inducing to prescribe biological rather than conventional immunosuppressants was quite different. Keywords: Autoantibody(ies), autoimmune disease, belimumab, cohort studies, glucocorticoids, immunosuppressants, rituximab, systemic lupus erythematosus


2019 ◽  
pp. 158-173

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder caused by a dopamine deficiency that presents with motor symptoms. Visual disorders can occur concomitantly but are frequently overlooked. Deep brain stimulation (DBS) has been an effective treatment to improve tremors, stiffness and overall mobility, but little is known about its effects on the visual system. Case Report: A 75-year-old Caucasian male with PD presented with longstanding binocular diplopia. On baseline examination, the best-corrected visual acuity was 20/25 in each eye. On observation, he had noticeable tremors with an unsteady gait. Distance alternating cover test showed exophoria with a right hyperphoria. Near alternating cover test revealed a significantly larger exophoria accompanied by a reduced near point of convergence. Additional testing with a 24-2 Humphrey visual field and optical coherence tomography (OCT) of the nerve and macula were unremarkable. The patient underwent DBS implantation five weeks after initial examination, and the device was activated four weeks thereafter. At follow up, the patient still complained of intermittent diplopia. There was no significant change in the manifest refraction or prism correction. On observation, the patient had remarkably improved tremors with a steady gait. All parameters measured were unchanged. The patient was evaluated again seven months after device activation. Although vergence ranges at all distances were improved, the patient was still symptomatic for intermittent diplopia. OCT scans of the optic nerve showed borderline but symmetric thinning in each eye. All other parameters measured were unchanged. Conclusion: The case found no significant changes on ophthalmic examination after DBS implantation and activation in a patient with PD. To the best of the authors’ knowledge, there are no other cases in the literature that investigated the effects of DBS on the visual system pathway in a patient with PD before and after DBS implantation and activation.


2014 ◽  
pp. 73-77
Author(s):  
Van Chuong Nguyen ◽  
Thi Kim Anh Nguyen

Background: A Research glomerular filtration rate (GFR) of 61 patients with type 2 diabetes mellitus with renal scanning 99mTc-DTPA glomerular filtration rate at the hospital 175. Objective: (1) To study characteristics of imaging of renal function. (2) Understanding the relationship between GFR with blood sugar, HbA1c, blood pressure and albuminuria in patients with type 2 diabetes. Methods: Descriptive, prospective, cross-sectional study. Clinical examination, Clinical tests and 99mTc-DTPA GFR gamma - camera renography for patients. Result: GFR of the study group was 75,4 ± 22,3 ml/phut/1,73m2, the left kidney was 35,0 ± 13,0 is lower than the right kidney and 39,8 ± 11,9; p <0,01. There is no correlation between GFR with blood glucose and HbA1c, the risk of reduced GFR in hypertensive group associated is OR = 6,5 with p<0,01; albuminuria (+) is OR = 4,2 with p <0,01; and disease duration > 10 years is OR = 3,5 with p <0.01. Conclusion: GFR of the left kidneys is lower than the right kidney; correlation decreased GFR associated with hypertension, albuminuria and disease duration. Keywords: GFR, diabetes, albuminuria


2021 ◽  
Vol 11 (7) ◽  
pp. 671
Author(s):  
Oihane Pikatza-Menoio ◽  
Amaia Elicegui ◽  
Xabier Bengoetxea ◽  
Neia Naldaiz-Gastesi ◽  
Adolfo López de Munain ◽  
...  

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that leads to progressive degeneration of motor neurons (MNs) and severe muscle atrophy without effective treatment. Most research on ALS has been focused on the study of MNs and supporting cells of the central nervous system. Strikingly, the recent observations of pathological changes in muscle occurring before disease onset and independent from MN degeneration have bolstered the interest for the study of muscle tissue as a potential target for delivery of therapies for ALS. Skeletal muscle has just been described as a tissue with an important secretory function that is toxic to MNs in the context of ALS. Moreover, a fine-tuning balance between biosynthetic and atrophic pathways is necessary to induce myogenesis for muscle tissue repair. Compromising this response due to primary metabolic abnormalities in the muscle could trigger defective muscle regeneration and neuromuscular junction restoration, with deleterious consequences for MNs and thereby hastening the development of ALS. However, it remains puzzling how backward signaling from the muscle could impinge on MN death. This review provides a comprehensive analysis on the current state-of-the-art of the role of the skeletal muscle in ALS, highlighting its contribution to the neurodegeneration in ALS through backward-signaling processes as a newly uncovered mechanism for a peripheral etiopathogenesis of the disease.


2021 ◽  
Vol 7 (2) ◽  
pp. 28
Author(s):  
Camille S. Corre ◽  
Dietrich Matern ◽  
Joan E. Pellegrino ◽  
Carlos A. Saavedra-Matiz ◽  
Joseph J. Orsini ◽  
...  

Krabbe disease (KD) is a rare inherited neurodegenerative disorder caused by a deficiency in galactocerebrosidase enzyme activity, which can present in early infancy, requiring an urgent referral for hematopoietic stem cell transplantation, or later in life. Newborn screening (NBS) for KD requires identification and risk-stratification of patients based on laboratory values to predict disease onset in early infancy or later in life. The biomarker psychosine plays a key role in NBS algorithms to ascertain probability of early-onset disease. This report describes a patient who was screened positive for KD in New York State, had a likely pathogenic genotype, and showed markedly reduced enzyme activity but surprisingly low psychosine levels. The patient ultimately developed KD in late infancy, an outcome not clearly predicted by existing NBS algorithms. It remains critical that psychosine levels be evaluated alongside genotype, enzyme activity levels, and the patient’s evolving clinical presentation, ideally in consultation with experts in KD, in order to guide diagnosis and plans for monitoring.


2016 ◽  
Vol 33 (S1) ◽  
pp. S147-S147
Author(s):  
M.D.C. Ferreira ◽  
S. Varanda ◽  
G. Carneiro ◽  
B. Santos ◽  
Á. Machado

IntroductionPsychosis is one of the most prevalent non-motor complications in Parkinson's disease (PD). Risk factors for PD psychosis are advancing age, longer disease duration, severe motor symptoms, presence of dementia, sleep disorders, depression and autonomic dysfunction. Treatment is challenging in this setting because antipsychotic medications are known to worse motor symptoms.ObjectivesTo highlight the therapeutic difficulties in PD-related psychosis.MethodsCase description and literature review.ResultsWe report a case of a 74-year-old woman with a 9-year history of PD, who presented a complex psychotic disorder consisting in auditory, olfactory and visual (gulliverian and lilliputian) hallucinations, persecutory and sexual delusions. Additionally, the patient presented euthymic mood, without evidence of cognitive impairment or impulse-control disorder. These symptoms began after dopamine agonist therapy (ropinirole 4 mg/day). Other medical conditions that could justify these symptoms were excluded. Initially, ropinirole was removed, but without psychotic remission. Then, she was treated with antipsychotic medication (clozapine 25 mg/day) with full psychotic remission and without significant worsening of motor symptoms.ConclusionsClozapine treatment is frequently delayed, mainly for fear of its side effects, particularly agranulocytosis. However, this antipsychotic drug presents many benefits regarding the management of PD-related psychosis, namely few motor effects and even improvement of motor fluctuations.Disclosure of interestThe authors have not supplied their declaration of competing interest.


Author(s):  
Anuja Sharma ◽  
Jaspreet Singh Anand ◽  
Yatender Kumar

: Alzheimer's Disease (AD), often called the 'Plague of the 21st Century,' is a progressive, irreversible neurodegenerative disorder that leads to the degeneration and death of neurons. Multiple factors, such as genetic defects, epigenetic regulations, environmental factors, or cerebrovascular damage, are a manifestation of the neurodegenerative process that begins to occur decades before the onset of disease. To date, no treatment or therapeutic strategy has proven to be potent in inhibiting its progress or reversing the effects of the disease. The ever-increasing numbers and lack of sufficient therapies that can control or reverse the effects of the disease have propelled research in the direction of devising efficient therapeutic strategies for AD. This review comprehensively discusses the active and passive immunotherapies against Amyloid-β and Tau protein, which remain the popular choice of targets for AD therapeutics. Some of the prospective immunotherapies against Aβ plaques have failed due to various reasons. Much of the research is focused on targeting Tau, specifically, targeting the mid-region of extracellular Tau due to their potential to prevent seeding and hence the spread of neurofibrillary tangles (NFTs). Thus, there is a need to thoroughly understand the disease onset mechanisms and discover effective therapeutic strategies.


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