PD As A Chronic Neurodegenerative Disease Essay

PD As A Chronic Neurodegenerative Disease Essay

It is estimated that 145,000 people suffer from Parkinson’s disease (PD) in the UK (1), with this figure predicted to rise by approximately 20% by 2025. PD is a chronic neurodegenerative disease for which there is no cure (2). It is caused by the death of nerve cells that make and replace dopamine from the substantia nigra of the basal ganglia and by the formation of lewy bodies (small proteins) in the brain cell (3). Without dopamine firing, the direct pathway, responsible for facilitating voluntary movements is interrupted. The 3 most common symptoms are resting tremor, rigidity and bradykinesia (1). PD As A Chronic Neurodegenerative Disease Essay.

However, as the disease progresses, non-motor symptoms as well as medication side effects start to appear e. g. hallucinations (4). I believe this study is of extreme importance and interest to health professionals and the NHS as the increasing prevalence of this disease means it is likely to cost the health system a lot of money in the future (5). I am a second year medical student of the University of Bristol. I have been set the task of discovering the effect of hospitalization on sufferers of PD as part of my student choice project in Musgrove hospital, Taunton. I aim to find out what symptoms people with PD present to the hospital with, to uncover the challenges patients with PD face in hospital and lastly, on the basis of the findings, to suggest measures to help patients overcome those challenges.

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Method: I identified different databases including Medline, Web of Sciences, PubMed, PMC, PsycINFO and searched for articles containing the keyword Parkinson’s and 2 or more of the following: inpatient, hospital, medication, experience and prevalence. I took note of my chosen research papers’ reference list for further material and to ensure I knew where each article was sourcing its information from. Additionally, I attended handover, ward rounds and spoke with patients who have PD as well as the multidisciplinary team looking after these patients. Results: Using the search methods above 40 articles were deemed relevant to the subject matter. I chose the most suitable 8 from this list which included the chosen studies’ and papers’ reference lists.

    1. Symptoms patients with PD present to the hospital with: There are a limited amount of resources and recent studies detailing the presenting complaint which people with PD arrive to the hospital with (9). One study reported that reduced functional ability, including falls (14%), fractures (4%) and general reduced physical ability (8%) was the most common reason patients with Parkinson’s were admitted to hospital (total 26%). Other reasons were infections (total 20%) including pneumonia (11%) and urinary tract infections (UTI) (9%) (6). Another study involving 260 emergency admissions of 173 patients with PD revealed 30% of admissions were to treat an infection (chest infection 22%, UTI 8%). Other reasons for admission included falls (13%), cardiovascular problems (5%), side effects of PD drugs (4%) and depression (3%) (7). During my placement in Taunton I saw 5 patients with PD: patient X had fractured her neck of femur (NOF), patient Y had been acutely confused and had fallen a day prior to admission, patient Z and W had come to hospital with worsening motor ability and patient A had fallen. PD As A Chronic Neurodegenerative Disease Essay.
    2. Challenges faced by patients with PD in hospital:
        1. MEDICATION

      Management of medication in Parkinson’s disease is one of the most challenging aspects of the syndrome.

      This becomes more challenging in a hospital setting for the following reasons

          • The timing of PD medication is very important. Most patients take their medication at specific times during the day and stick to this rigorously (8).
          • The frequency of medication differs from most other medication and can occur up to 5 times a day (9).
          • PD medication can be complex with many different drug combinations and doses.

      Hence this can make life difficult for a patient with PD in the following ways:

          • It can take a long time for a patient’s medication list to be sent from the patients GP surgery to the doctor to the pharmacist.
          • During this time a patient may have missed 2 medication rounds (10).
          • Most medications in hospital are given at a particular time (morning, lunch, evening) whereas PD medications may need to be given at atypical times e. g. 16: 00 hrs (10).
          • Depending on the reason for admission e. g. acute confusion, medication may need to be reviewed and modified. This takes time and could delay administration of medication.
          • Events such as surgery mean medication is stopped pre and postoperatively. One study in Aberdeen Royal Infirmary discovered that during 59 surgical admissions of 51 patients with PD, over 70% of admissions resulted in medication being missed during the patients stay at hospital (11).
        1. LACK OF PD EXPERTISE

      Most patients with PD presenting to the hospital are sent to general wards rather than neurology wards (12), where staff have limited knowledge of PD (9). A retrospective audit was carried out in the Princess Royal University of North Kent that highlighted the challenges faced by doctors and nurses when a patient with PD enters their ward.PD As A Chronic Neurodegenerative Disease Essay.  It showed that only 1 of 16 pre-registrar house officers understood the function of apomorphine (dopamine agonist) and 5 of 20 could name one drug that should not be given to a patient suffering from PD. 26 of 35 patients with PD either didn’t get the correct medication or got no medication, resulting in patients becoming constipated and their muscles stiffening (13).

      1. ENVIRONMENTA further difficulty in relation to general wards is that the environment may not be favourable. It might not be designed to give sufficient time to the patients to carry out basic activities, e. g. mobilising, eating and speaking. Sometimes there is not enough access to physiotherapy which is very important for patients with PD.
    3. Patient view on experience in the hospital

To supplement my reading and research, I planned to talk with various different patients with PD who entered the hospital over the course of three weeks. However, only one patient was able to converse with me. Thus it was necessary to speak with several members of staff to get more information. Patient X was admitted to the orthopaedic ward with a fractured NOF. After the procedure she did not receive pain medication immediately as the staff on the orthopaedic ward were unsure how such medication would interact with the PD medication. This patient had a further complication as she had a duodopa pump (liquid form of levodopa that is more potent than oral tablets). She had to be transferred to a ward with PD specialists. PD As A Chronic Neurodegenerative Disease Essay.

During this time her pain relief medication as well as her routine PD drugs were delayed leading to further complications such as low mood. Patient X was too unwell to speak with me so I got the case history from one of the consultant geriatricians on the ward. Patient Y was able to converse with me. He came in with severe confusion following a fall. He told me he often does not get his medication at the times he is used to. Patient Y’s main complaint now is that his muscles are very stiff and he finds it hard to get out of bed or go for short walks. The physiotherapist confirmed that patient Y has been unable to engage fully with his last 2 physio appointments during his time in hospital. He is in a bay with 7 other patients none of whom have the same condition. He finds it hard to sleep at night as it’s very noisy with bells ringing regularly. Patient Z and W have been very anxious since last week, mainly due to a new patient with dementia having been admitted to their bay.

Discussion

From my research and time spent on the wards, it would appear that patients with PD are admitted for several different reasons, some directly related to PD (decreased functional mobility), some indirectly related to PD (side effects of medication e. g. hallucinations, depression) and some possibly unrelated such as infections (7). However, for this question to be answered more conclusively, more studies would need to be conducted on the presenting complaints of patients with PD attending hospital. In addition I would visit more hospitals in order to see more patients and thus accumulate more reliable data. PD As A Chronic Neurodegenerative Disease Essay. As we can see from the results above, there are significant obstacles for a patient with PD in hospital. When PD medication is missed, given late or the wrong dose is administered, the patient becomes unwell (13) as is illustrated by patients X’s and Y’s experience. Patient X has already been in hospital 3 weeks. People without PD getting a hip replacement usually leave the hospital approximately 26 hours after the procedure (14).

Similarly, patient Y has been an inpatient for the last 2 weeks. His acute confusion and decreased functional mobility has worsened since his admission which may be partly due to mistimed medication. It appears that a patient’s stay in hospital is lengthened if they have PD. One study conducted over a 4 year period revealed patients’ average stay in hospital was 3. 5 days longer than patients without PD, 21. 3 versus 17. 8 (6). I believe the obstacles mentioned above contribute to this.

Conclusion

I wished to investigate if a hospital setting provided significant challenges for patients with PD. I researched several studies and articles on the subject matter, I spoke with all members of the multidisciplinary team including doctors, nurses, physiotherapists, occupational therapists social care workers, home first co-ordinators and spoke and observed patients on the wards where possible. It is clear PD is a very specialised disorder that requires extensive knowledge of the disease, including understanding the importance of regular administration of medication at specific times and of appropriate therapies. Patients with PD are regularly treated by health care professionals that are not experts in their condition and this can pose problems that ultimately mean patients with PD stay longer in hospital than patients without PD. RecommendationsIn view of the potential detrimental effects through admission to hospital, it may be beneficial to make more use of day hospital type management. For example where the presenting problem is decreased motor ability, the person could attend a day hospital regularly for monitoring medication changes and intensive physiotherapy. In relation to inpatient care I think there should be more specific education.

This would hopefully lead to less errors being made regarding treatment. Where the patient can’t be in a specialised unit a more integrated approach to their care would be beneficial, e. g. involvement of a geriatrician on an orthopaedic ward. PD As A Chronic Neurodegenerative Disease Essay.

In addition, the patient with PD could be identified early during admission for physiotherapy input. Lastly, some simple approaches in a hospital to encourage mobility would also benefit the patient with PD. The NHS campaign ‘End PJ Paralysis’ encourages hospital staff to get patients up, dressed and out of pyjamas and moving while in hospital. Patients with PD that are bed bound in hospital lose motor ability. This simple initiative could particularly benefit the patients with PD make one’s experience in hospital more enjoyable and shorter.

Reflection

This has been such a worthwhile project as I have learned so much in a field that I had little experience in. Before I started this project all I knew about PD was that it resulted from a reduction in dopamine firing in the brain. However, I now have a comprehensive awareness of the disease, it’s prevalence, the symptoms as well as the treatment side effects. Most importantly I have gained invaluable insights into a patient’s perspective of having the disease in a hospital setting. Throughout this project I have practiced talking to patients and listening in an active manner. I have learned the layout of the charts and I have observed how to clerk a patient. This project has inspired me to do further research on the subject matter possibly during my intercalation year or after I finish medical school.

Alzheimer’s disease and Parkinson’s disease are characterized as a chronic and progressive neurodegenerative disorder and are manifested by the loss of neurons within the brain and/or spinal cord. In the present chapter, we would like to summarize the molecular mechanism focusing on metabolic modification associated with neurodegenerative diseases or heritable genetic disorders.  PD As A Chronic Neurodegenerative Disease Essay.The identification of the exact molecular mechanisms involved in these diseases would facilitate the discovery of earlier pathophysiological markers along with substantial therapies, which may consist (of) mitochondria-targeted antioxidant therapy, mitochondrial dynamics modulators, epigenetic modulators, and neural stem cell therapy. Therefore, all these therapies may hold particular assurance as influential neuroprotective therapies in the treatment of neurodegenerative diseases.

Keywords

  • neurons
  • mitochondria-targeted antioxidants
  • mitochondrial dynamics
  • epigenetic regulations
  • stem cell
  • neurodegenerative diseases

1.1 What are neurons?

Neurons or nerve cells are the functional unit of the brain and nervous system, and they produce electrical signals known as action potentials. Action potentials permit them to speedily pass on the details over long distances. Their connections define who we are as a person. The creation of new neurons in the brain is known as neurogenesis [1].

1.2 Anatomy of a neuron

Different types of neurons may differ in a number of ways, but they all include three distinct regions with differing functions, that is, the cell body (soma), followed by the dendrites, the axons, and the connected axon terminals (Figure 1).

  1. Cell body: It is the place of biogenesis of almost all neuronal proteins and membranes. It contains a nucleus.

  2. Dendrites: The extensions of neurons that receive signals and conduct them toward the cell body (soma) are known as dendrites.

  3. Axon (nerve fiber): The extensions of neurons that conduct the signals away from the cell body to the other nerve cells or neuron are known as axons.

  4. Axon terminal (end-plate): The end part or terminal part of axons that makes a synaptic contact with other nerve cells is known as an axon terminal. PD As A Chronic Neurodegenerative Disease Essay. It is responsible for the initiation of transmission of nerve impulse to another nerve cell [2].

Figure 1.

Anatomy of neuron.

1.3 Functions of neurons

  1. Conduction and transmission of nerve impulses

  2. Initiation and conduction of action potential

  3. Synaptic transmission [3]

1.4 How neurons transmit information throughout the body?

Neurons converse with other neurons through axons and dendrites. When a neuron receives information from another neuron, it transmits an electrical signal along the length of the respective axon, known as action potential. At the axon terminal, the electrical signal is changed into chemical signal. The axon releases chemical messengers called neurotransmitters. The neurotransmitters are released into the gap between the axon terminal and the tip of a dendrite (receptor site) of a further neuron. PD As A Chronic Neurodegenerative Disease Essay. The space between the axon terminal and the tip of a dendrite is called a synapse. The neurotransmitters travel along the short distance through the synaptic gap to the dendrite. The dendrite receives the neurotransmitters and translates the chemical signal into electrical signal. This electrical signal travels all the way through the neuron, to be converted back into a chemical signal when it gets to adjoining neurons [4].

2. Neurodegenerative diseases

Etymologically, the word neurodegeneration comprises of “neuro,” which refers to neurons, and “degeneration,” which refers to the process of losing structure and/or function of either tissues or organs [5]. A neurodegenerative disease is considered as a slow, progressive failure of nerve cells within the central nervous system (CNS). This leads to deficits in particular brain functions like learning, movement, and cognition generally performed by the CNS (brain and spinal cord).

2.1 Factors associated with neurodegenerative diseases

  1. Aberrant protein dynamics with aggregation and degradation of defective protein [6]

  2. Oxidative stress and reactive oxygen species (ROS) formation

  3. Impaired bioenergetics and mitochondrial dysfunction

  4. Excessive exposure to metals and pesticides (Figure 2)

Figure 2.

Factors associated with neurodegenerative diseases.

2.2 Classification based on molecular defects

  1. Trinucleotide repeat diseases: HD, spinal cerebellar atrophy, and myotonic dystrophy [7].

  2. Prion diseases: Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker syndrome, and fetal familial insomnia [8]. PD As A Chronic Neurodegenerative Disease Essay.

  3. Synucleinopathies: PD, progressive supranuclear palsy and diffuse Lewy body dementia [9].

  4. Tauopathies: Corticobasal degeneration, frontotemporal dementia with parkinsonism linked to chromosome 1\(FTDP-17), and pick disease [10].

3. Alzheimer’s disease

Alzheimer’s disease (AD) is an irreparable, progressive neurodegenerative disease that affects normal brain functioning [11]. It is mainly the general cause of dementia [12]. Dementia is a syndrome associated with memory loss and loss of abilities like thinking, reasoning, and language skills along with other mental illness [12].

3.1 History

This disease is named after Dr. Alois Alzheimer. He observed some brain tissue abnormalities in an old woman who died due to some unusual mental illness. Later, he examined her brain and found many abnormal tangled bundles of fibers (called as tau tangles, neurofibrillary) and clumps (called as amyloid plaques). That is how he found the cause of AD [13].

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3.2 Causes

The cause of AD is not clearly understood.

  1. Genetic: Nearly, 70% of the cases are related to genetic factors with the involvement of many specific genes [14].

    1. Autosomal dominant inheritance: Also known as early-onset familial AD [15], it occurs due to the mutation in one of the three genes: Presenilin 1, presenilin 2, or amyloid precursor protein (APP) [16].

      Aβ42: A protein that is the main component of senile plaques, and the levels are increased due to mutation in APP and presenilin genes [17]. PD As A Chronic Neurodegenerative Disease Essay.

    2. Sporadic Alzheimer’s disease: In this type of AD, genetic and environmental factors play a major role.

      Example: Inheritance of the epsilon 4 allele of the apolipoprotein E (APOE) [18, 19].

  2. Cholinergic hypothesis: The cholinergic hypothesis states that AD is caused by the reduced synthesis of neurotransmitter acetylcholine [20].

  3. Amyloid hypothesis: The amyloid hypothesis states that AD is caused by the deposits of extracellular amyloid beta (Aβ) [21].

  4. Tau hypothesis: The tau hypothesis states that AD is caused due to abnormalities in tau protein, leading to the disintegration of microtubules in nerve cells [22, 23].

3.3 Molecular mechanism

(a) Proteopathy: AD has been recognized by plaque formation occurring due to abnormal folding of amyloid beta (Aβ) protein and tau protein in the nerve cells (brain) leading to the degeneration of nerve cells [24]. The amyloid precursor protein (APP) leads to the formation of Aβ. APP plays an important role in neuron-like developments and post-injury repair mechanism and survival [25, 26]. In AD, secreting enzymes like β-secretase and γ-secretase together will break down APP into small fragments that penetrate through the neuron membrane [27]. This leads to the formation of Aβ fibrils that later cluster together to form senile plaques and deposits in the outer side of neurons [28, 29]. Aggregated amyloid fibrils accumulation leads to the disruption of cell’s calcium ion homeostasis, which results in apoptosis [30] (Figure 3). PD As A Chronic Neurodegenerative Disease Essay.

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