Parkinson's Disease – An Unusual Case of Prolonged Invasive Home Ventilation

Parkinson's disease is a neurodegenerative disorder characterized by muscle rigidity, tremor, slowing or loss of physical movement. The impact of the disease is indicated by the fact that mortality is two to five times as high among affected persons as among age matched controls resulting in reduction in life expectancy. Amongst the motor dysfunction, swallowing disturbances can lead to drooling and impaired ability to swallow. These could cause aspiration pneumonia and death. We report a case of prolonged invasive home ventilation. Patient needs four hours of ventilation a day and uses Passy Muir Valve PMV 2000 for speech. JMS 2013;16(2):97-98

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A multinational consensus on dysphagia in Parkinson's disease: screening, diagnosis and prognostic value

Journal of Neurology ◽

10.1007/s00415-021-10739-8 ◽

2021 ◽

Author(s):

Giuseppe Cosentino ◽

Micol Avenali ◽

Antonio Schindler ◽

Nicole Pizzorni ◽

Cristina Montomoli ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Prognostic Value ◽

Neurodegenerative Disorder ◽

Consensus Conference ◽

Motor Dysfunction ◽

Common Symptom ◽

Neurogenic Dysphagia ◽

Consensus Statements ◽

The Impact

Abstract Background Parkinson’s disease (PD) is a neurodegenerative disorder characterized by a combination of motor and non-motor dysfunction. Dysphagia is a common symptom in PD, though it is still too frequently underdiagnosed. Consensus is lacking on screening, diagnosis, and prognosis of dysphagia in PD. Objective To systematically review the literature and to define consensus statements on the screening and the diagnosis of dysphagia in PD, as well as on the impact of dysphagia on the prognosis and quality of life (QoL) of PD patients. Methods A multinational group of experts in the field of neurogenic dysphagia and/or PD conducted a systematic revision of the literature published since January 1990 to February 2021 and reported the results according to PRISMA guidelines. The output of the research was then analyzed and discussed in a consensus conference convened in Pavia, Italy, where the consensus statements were drafted. The final version of statements was subsequently achieved by e-mail consensus. Results Eighty-five papers were used to inform the Panel’s statements even though most of them were of Class IV quality. The statements tackled four main areas: (1) screening of dysphagia: timing and tools; (2) diagnosis of dysphagia: clinical and instrumental detection, severity assessment; (3) dysphagia and QoL: impact and assessment; (4) prognostic value of dysphagia; impact on the outcome and role of associated conditions. Conclusions The statements elaborated by the Consensus Panel provide a framework to guide the neurologist in the timely detection and accurate diagnosis of dysphagia in PD.

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Validation of Cognitive Rehabilitation as a Balance Rehabilitation Strategy in Patients with Parkinson’s Disease: Study Protocol for a Randomized Controlled Trial

Medicina ◽

10.3390/medicina57040314 ◽

2021 ◽

Vol 57 (4) ◽

pp. 314

Author(s):

Aida Arroyo-Ferrer ◽

Francisco José Sánchez-Cuesta ◽

Yeray González-Zamorano ◽

María Dolores del Castillo ◽

Carolina Sastre-Barrios ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Therapy ◽

Cognitive Processing ◽

Processing Speed ◽

Cognitive Rehabilitation ◽

Neurodegenerative Disorder ◽

Control Group ◽

Motor Symptoms ◽

The Impact

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder. This disease is characterized by motor symptoms, such as bradykinesia, tremor, and rigidity. Although balance impairment is characteristic of advanced stages, it can be present with less intensity since the beginning of the disease. Approximately 60% of PD patients fall once a year and 40% recurrently. On the other hand, cognitive symptoms affect up to 20% of patients with PD in early stages and can even precede the onset of motor symptoms. There are cognitive requirements for balance and can be challenged when attention is diverted or reduced, linking a worse balance and a higher probability of falls with a slower cognitive processing speed and attentional problems. Cognitive rehabilitation of attention and processing speed can lead to an improvement in postural stability in patients with Parkinson’s. Methods: We present a parallel and controlled randomized clinical trial (RCT) to assess the impact on balance of a protocol based on cognitive rehabilitation focused on sustained attention through the NeuronUP platform (Neuronup SI, La Rioja, Spain) in patients with PD. For 4 weeks, patients in the experimental group will receive cognitive therapy three days a week while the control group will not receive any therapy. The protocol has been registered at trials.gov NCT04730466. Conclusions: Cognitive therapy efficacy on balance improvement may open the possibility of new rehabilitation strategies for prevention of falls in PD, reducing morbidity, and saving costs to the health care system.

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Potential Role of Caffeine in the Treatment of Parkinson’s Disease

The Open Neurology Journal ◽

10.2174/1874205x01610010042 ◽

2016 ◽

Vol 10 (1) ◽

pp. 42-58 ◽

Cited By ~ 8

Author(s):

Mohsin H.K. Roshan ◽

Amos Tambo ◽

Nikolai P. Pace

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Randomized Clinical Trials ◽

Neurodegenerative Disorder ◽

Lewy Bodies ◽

Substantia Nigra Pars Compacta ◽

Muscle Rigidity ◽

Therapeutic Effects ◽

Motor Symptoms ◽

Wide Range

Parkinson’s disease [PD] is the second most common neurodegenerative disorder after Alzheimer’s disease, affecting 1% of the population over the age of 55. The underlying neuropathology seen in PD is characterised by progressive loss of dopaminergic neurons in the substantia nigra pars compacta with the presence of Lewy bodies. The Lewy bodies are composed of aggregates of α-synuclein. The motor manifestations of PD include a resting tremor, bradykinesia, and muscle rigidity. Currently there is no cure for PD and motor symptoms are treated with a number of drugs including levodopa [L-dopa]. These drugs do not delay progression of the disease and often provide only temporary relief. Their use is often accompanied by severe adverse effects. Emerging evidence from bothin vivoandin vitrostudies suggests that caffeine may reduce parkinsonian motor symptoms by antagonising the adenosine A2Areceptor, which is predominately expressed in the basal ganglia. It is hypothesised that caffeine may increase the excitatory activity in local areas by inhibiting the astrocytic inflammatory processes but evidence remains inconclusive. In addition, the co-administration of caffeine with currently available PD drugs helps to reduce drug tolerance, suggesting that caffeine may be used as an adjuvant in treating PD. In conclusion, caffeine may have a wide range of therapeutic effects which are yet to be explored, and therefore warrants further investigation in randomized clinical trials.

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Peptide TFP5/TP5 derived from Cdk5 activator P35 provides neuroprotection in the MPTP model of Parkinson’s disease

Molecular Biology of the Cell ◽

10.1091/mbc.e15-06-0415 ◽

2015 ◽

Vol 26 (24) ◽

pp. 4478-4491 ◽

Cited By ~ 19

Author(s):

BK. Binukumar ◽

Varsha Shukla ◽

Niranjana D. Amin ◽

Philip Grant ◽

M. Bhaskar ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Neurodegenerative Disorder ◽

Neuroprotective Effect ◽

Selective Inhibition ◽

Motor Dysfunction ◽

Dopamine Neurons ◽

Dopamine Depletion ◽

Neuroprotective Effects

Parkinson’s disease (PD) is a chronic neurodegenerative disorder characterized by the loss of dopamine neurons in the substantia nigra, decreased striatal dopamine levels, and consequent extrapyramidal motor dysfunction. Recent evidence indicates that cyclin-dependent kinase 5 (Cdk5) is inappropriately activated in several neurodegenerative conditions, including PD. To date, strategies to specifically inhibit Cdk5 hyperactivity have not been successful without affecting normal Cdk5 activity. Previously we reported that TFP5 peptide has neuroprotective effects in animal models of Alzheimer’s disease. Here we show that TFP5/TP5 selective inhibition of Cdk5/p25 hyperactivation in vivo and in vitro rescues nigrostriatal dopaminergic neurodegeneration induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP/MPP+) in a mouse model of PD. TP5 peptide treatment also blocked dopamine depletion in the striatum and improved gait dysfunction after MPTP administration. The neuroprotective effect of TFP5/TP5 peptide is also associated with marked reduction in neuroinflammation and apoptosis. Here we show selective inhibition of Cdk5/p25 hyperactivation by TFP5/TP5 peptide, which identifies the kinase as a potential therapeutic target to reduce neurodegeneration in Parkinson’s disease.

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Palmitate and Stearate are Increased in the Plasma in a 6-OHDA Model of Parkinson’s Disease

Metabolites ◽

10.3390/metabo9020031 ◽

2019 ◽

Vol 9 (2) ◽

pp. 31 ◽

Cited By ~ 1

Author(s):

Anuri Shah ◽

Pei Han ◽

Mung-Yee Wong ◽

Raymond Chang ◽

Cristina Legido-Quigley

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Stearic Acid ◽

Palmitic Acid ◽

Neurodegenerative Disorder ◽

Motor Dysfunction ◽

Substantia Nigra Pars Compacta ◽

Control Group ◽

Sprague Dawley ◽

Curative Therapy

Introduction: Parkinson’s disease (PD) is the second most common neurodegenerative disorder, without any widely available curative therapy. Metabolomics is a powerful tool which can be used to identify unexpected pathway-related disease progression and pathophysiological mechanisms. In this study, metabolomics in brain, plasma and liver was investigated in an experimental PD model, to discover small molecules that are associated with dopaminergic cell loss. Methods: Sprague Dawley (SD) rats were injected unilaterally with 6-hydroxydopamine (6-OHDA) or saline for the vehicle control group into the medial forebrain bundle (MFB) to induce loss of dopaminergic neurons in the substantia nigra pars compacta. Plasma, midbrain and liver samples were collected for metabolic profiling. Multivariate and univariate analyses revealed metabolites that were altered in the PD group. Results: In plasma, palmitic acid (q = 3.72 × 10−2, FC = 1.81) and stearic acid (q = 3.84 × 10−2, FC = 2.15), were found to be increased in the PD group. Palmitic acid (q = 3.5 × 10−2) and stearic acid (q = 2.7 × 10−2) correlated with test scores indicative of motor dysfunction. Monopalmitin (q = 4.8 × 10−2, FC = −11.7), monostearin (q = 3.72 × 10−2, FC = −15.1) and myo-inositol (q = 3.81 × 10−2, FC = −3.32), were reduced in the midbrain. The liver did not have altered levels of these molecules. Conclusion: Our results show that saturated free fatty acids, their monoglycerides and myo-inositol metabolism in the midbrain and enteric circulation are associated with 6-OHDA-induced PD pathology.

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Impact of Aging on the 6-OHDA-Induced Rat Model of Parkinson’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms21103459 ◽

2020 ◽

Vol 21 (10) ◽

pp. 3459 ◽

Cited By ~ 2

Author(s):

Sandra Barata-Antunes ◽

Fábio G. Teixeira ◽

Bárbara Mendes-Pinheiro ◽

Ana V. Domingues ◽

Helena Vilaça-Faria ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Animal Welfare ◽

Neurodegenerative Disorder ◽

Negative Impact ◽

Substantia Nigra Pars Compacta ◽

Nigrostriatal Pathway ◽

Aged Rats ◽

Age Related ◽

The Impact

Parkinson’s disease (PD) is the second most common age-related neurodegenerative disorder. The neurodegeneration leading to incapacitating motor abnormalities mainly occurs in the nigrostriatal pathway due to the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Several animal models have been developed not only to better understand the mechanisms underlying neurodegeneration but also to test the potential of emerging disease-modifying therapies. However, despite aging being the main risk factor for developing idiopathic PD, most of the studies do not use aged animals. Therefore, this study aimed at assessing the effect of aging in the unilateral 6-hydroxydopamine (6-OHDA)-induced animal model of PD. For this, female young adult and aged rats received a unilateral injection of 6-OHDA into the medial forebrain bundle. Subsequently, the impact of aging on 6-OHDA-induced effects on animal welfare, motor performance, and nigrostriatal integrity were assessed. The results showed that aging had a negative impact on animal welfare after surgery. Furthermore, 6-OHDA-induced impairments on skilled motor function were significantly higher in aged rats when compared with their younger counterparts. Nigrostriatal histological analysis further revealed an increased 6-OHDA-induced dopaminergic cell loss in the SNpc of aged animals when compared to young animals. Overall, our results demonstrate a higher susceptibility of aged animals to 6-OHDA toxic insult.

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Probiotics Treatment Improves Hippocampal Dependent Cognition in a Rodent Model of Parkinson’s Disease

Microorganisms ◽

10.3390/microorganisms8111661 ◽

2020 ◽

Vol 8 (11) ◽

pp. 1661

Author(s):

Caroline Xie ◽

Asheeta A. Prasad

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Psychiatric Symptoms ◽

Neuropsychiatric Symptoms ◽

Motor Dysfunction ◽

Adjunctive Treatment ◽

Motor Symptoms ◽

Post Surgery ◽

Probiotic Treatment ◽

The Impact

Parkinson’s disease (PD) is a neurological disorder with motor dysfunction and a number of psychiatric symptoms. Symptoms such as anxiety and cognitive deficits emerge prior to motor symptoms and persist over time. There are limited treatments targeting PD psychiatric symptoms. Emerging studies reveal that the gut microbe is altered in PD patients. Here we assessed the effect of a probiotic treatment in a rat model of PD. We used the neurotoxin (6-hydroxydopamine, 6-OHDA) in a preclinical PD model to examine the impact of a probiotic treatment (Lacticaseibacillus rhamnosus HA-114) on anxiety and memory. Rats underwent either sham surgery or received 6-OHDA bilaterally into the striatum. Three weeks post-surgery, rats were divided into three experimental groups: a sham group that received probiotics, a 6-OHDA group that received probiotics, and the third group of 6-OHDA received the placebo formula. All rats had access to either placebo or probiotics formula for 6 weeks. All groups were assessed for anxiety-like behaviour using the elevated plus maze. Cognition was assessed for both non-hippocampal and hippocampal dependent tasks using the novel object recognition and novel place recognition. We report that the 6-OHDA lesion induced anxiety-like behaviour and deficits in hippocampal dependent cognition. Interestingly, the probiotics treatment had no impact on anxiety-like behaviour but selectively improved hippocampal dependent cognition deficits. Together, the results presented here highlight the utility of animal models in examining the neuropsychiatric symptoms of PD and the potential of probiotics as adjunctive treatment for non-motor symptoms of PD.

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Editorial for the Special Issue “Animal Models of Parkinson’s Disease and Related Disorders”

International Journal of Molecular Sciences ◽

10.3390/ijms21124250 ◽

2020 ◽

Vol 21 (12) ◽

pp. 4250

Author(s):

Yuzuru Imai

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Animal Models ◽

Dopaminergic Neurons ◽

Neurodegenerative Disorder ◽

Motor Dysfunction ◽

Special Issue ◽

Midbrain Dopaminergic Neurons ◽

Age Dependent ◽

Common Neurodegenerative Disorder

Parkinson’s disease (PD) is the second most common neurodegenerative disorder characterized by age-dependent motor dysfunction and degeneration of the midbrain dopaminergic neurons [...]

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The Neuro-Protective Effects of the TSPO Ligands CB86 and CB204 on 6-OHDA-Induced PC12 Cell Death as an In Vitro Model for Parkinson’s Disease

Biology ◽

10.3390/biology10111183 ◽

2021 ◽

Vol 10 (11) ◽

pp. 1183

Author(s):

Sheelu Monga ◽

Nunzio Denora ◽

Valentino Laquintana ◽

Rami Yashaev ◽

Abraham Weizman ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cell Death ◽

Neurodegenerative Disorder ◽

Reactive Oxygen ◽

Ros Generation ◽

Oxygen Species ◽

The Impact

Parkinson’s disease (PD) is a progressive neurodegenerative disorder which is characterized by the degeneration of dopaminergic neurons in substantia nigra (SN). Oxidative stress or reactive oxygen species (ROS) generation was suggested to play a role in this specific type of neurodegeneration. Therapeutic options which can target and counteract ROS generation may be of benefit. TSPO ligands are known to counteract with neuro-inflammation, ROS generation, apoptosis, and necrosis. In the current study, we investigated an in vitro cellular PD model by the assessment of 6-hydroxydopamine (6-OHDA, 80 µM)-induced PC12 neurotoxicity. Simultaneously to the exposure of the cells to 6-OHDA, we added the TSPO ligands CB86 and CB204 (25 µM each) and assessed the impact on several markers of cell death. The two ligands normalized significantly (57% and 52% respectively, from 44%; whereas the control was 68%) cell proliferation at different time points from 0–24 h. Additionally, we evaluated the effect of these two TSPO ligands on necrosis using propidium iodide (PI) staining and found that the ligands inhibited significantly the 6-OHDA-induced necrosis. As compared to control, the red count was increased up to 57-fold whereas CB86 and CB204 inhibited to 2.7-fold and 3.2-fold respectively. Necrosis was also analyzed by LDH assay which showed significant effect. Both assays demonstrated similar potent anti-necrotic effect of the two TSPO ligands. Reactive oxygen species (ROS) generation induced by 6-OHDA was also inhibited by the two TSPO ligand up to 1.3 and 1.5-fold respectively, as compared to 6-OHDA group. CB86 and CB204 inhibited also normalized the cell viability up to 1.8-fold after the exposure to 6-OHDA, as assessed by XTT assay. The two TSPO ligands also inhibited apoptosis significantly (1.3-fold for both) as assessed by apopxin green staining. In summary, it appears that the two TSPO ligands CB86 and CB204 can suppress cell death of PC12 induced by 6-OHDA. The results may be relevant to the use of these two TSPO ligands as therapeutic option neurodegenerative diseases like PD.

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Levodopa Therapy for Parkinson's Disease: History, Current Status and Perspectives

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527319666200722153156 ◽

2020 ◽

Vol 19 (8) ◽

pp. 572-583

Author(s):

Helle Bogetofte ◽

Arezo Alamyar ◽

Morten Blaabjerg ◽

Morten Meyer

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Side Effects ◽

Dopaminergic Neurons ◽

Neurodegenerative Disorder ◽

Neuroprotective Effect ◽

Substantia Nigra Pars Compacta ◽

Current Status ◽

Current Evidence ◽

Muscle Rigidity

Parkinson’s Disease (PD) is a neurodegenerative disorder characterized by a preferential degeneration of dopaminergic neurons in the substantia nigra pars compacta. This results in a profound decrease of striatal dopamine (DA) levels, which in turn leads to the cardinal motor symptoms of PD; muscle rigidity, hypo- and bradykinesia and resting tremor. Even 50 years after its initial use, the DA precursor levodopa (L-dopa), is still the most effective medical therapy for the symptomatic treatment of PD. Long-term L-dopa treatment is however, unfortunately associated with undesirable side effects such as motor fluctuations and dyskinesias. Furthermore, despite the disease alleviating effects of L-dopa, it is still discussed whether L-dopa has a neurotoxic or neuroprotective effect on dopaminergic neurons. Here we review the history of L-dopa, including its discovery, development and current use in the treatment of PD. We furthermore review current evidence of the L-dopa-induced side effects and perspectives of L-dopa treatment in PD compared to other established treatments such as DA-agonists and the inhibitors of catechol-o-methyltransferase and monoamine oxidase B.

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