Neurological conditions are diseases that affect the nervous system, which includes the brain, spinal cord and nerves (Peate, 2021). These conditions can have a profound impact on a person's daily life, causing a range of symptoms from memory loss to difficulty moving. Although the pathophysiology of each condition is unique, many share some commonalities.
Alzheimer's disease
Alzheimer's is a neurodegenerative disorder affecting approximately 50 million people worldwide (Breijyeh and Karaman, 2020), making it the most common cause of dementia among older adults. The pathophysiology of Alzheimer's disease is complex and not yet fully understood, but research has identified key changes in the brain that occur in individuals with the disease.
One of the hallmarks of Alzheimer's disease is the accumulation of beta-amyloid plaques and tau protein tangles in the brain. Beta-amyloid is a protein fragment that is derived from the amyloid precursor protein. It aggregates to form plaques between neurons, causing disruption in the communication pathways between them. Tau protein is involved in maintaining the structural integrity of the neurons, but in Alzheimer's disease, it forms tangles within the neurons, causing them to collapse. These abnormal protein deposits interfere with the normal functioning of neurons, leading to cell death and brain atrophy (Huang and Mucke, 2012).
In addition to these changes, inflammation has also been identified as a key contributor to the development of Alzheimer's. Microglia, the resident immune cells in the brain, play a crucial role in maintaining brain health, but they also contribute to inflammation in response to beta-amyloid plaques. Chronic inflammation in the brain can damage neurons, contributing to the progression of the disease (Heneka et al, 2015).
Understanding the underlying pathophysiology of Alzheimer's disease is crucial for the development of effective treatments and interventions. Current findings provide valuable insights into the mechanisms involved in the development and progression of the condition.
It is important to note that Alzheimer's progresses differently in each individual, and not everyone will experience all the symptoms associated with the condition. Box 1 provides an overview of the main symptoms commonly associated with Alzheimer's.
Box 1.Common symptoms associated with Alzheimer's disease
- Memory loss
- Disorientation and confusion
- Difficulty with problem solving and planning
- Language problems
- Poor judgement
- Misplacing items
- Mood and personality changes
- Difficulty in completing familiar tasks
- Withdrawal from social activities
- Changes in hygiene and self-care
Parkinson's
Parkinson's is a progressive neurological condition affecting movement, which is caused by the degeneration of dopamine-producing neurons in the brain (Olanow and Tatton, 1999). Dopamine plays a crucial role in the regulation of movement, so the loss of these neurons leads to the characteristic motor symptoms of Parkinson's disease, such as tremors and rigidity (Kalia and Lang, 2015).
The substantia nigra is a small part of the brain that produces dopamine, which helps control movement. In Parkinson's, the cells in the substantia nigra that produce dopamine stop working properly or die, leading to a shortage of dopamine in the brain. Basal ganglia (located deep within the brain, primarily in the cerebral hemispheres) act as a control centre for movement, using dopamine to transmit signals to different parts of the brain controlling how we move. Insufficient dopamine from the substantia nigra leads to these signals being misinterpreted. As a result, people with Parkinson's can have problems with their movements (see Box 2).
Box 2.Common symptoms in Parkinson's
- Tremors
- Bradykinesia
- Muscle rigidity
- Postural instability
- Akinesia
- Freezing of gait
- Micrographia
- Speech and swallowing difficulties
- Mask-like expression
- Non-motor symptoms
The pathophysiology of Parkinson's also involves the accumulation of abnormal protein deposits in the brain. In this case, the protein alpha-synuclein forms clumps called Lewy bodies, which interfere with the normal functioning of neurons (Spillantini and Goedert, 2013). These protein deposits also activate immune cells in the brain, leading to chronic inflammation (Qin et al, 2016).
Researchers have, in addition, identified inflammation as a key contributor to the development of Parkinson's. Such inflammatory processes can contribute to the degeneration of dopamine-producing neurons and accelerate the progression of the disease (L'Episcopo et al, 2018). An increase in inflammatory cytokines, such as tumour necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), has been identified in the brains of people with Parkinson's (Sriram et al, 2002).
Parkinson's is a progressive condition, so it should be noted that individuals may experience symptoms to varying degrees and at different rates of progression. Box 2 provides an outline of symptoms associated with Parkinson's; and see Case Study.
Multiple sclerosis
The nervous system consists of the central nervous system (CNS), including the brain and spinal cord, and the peripheral nervous system, which connects the CNS to the rest of the body (Figure 1). The CNS, encased in the skull and spine, processes information received from the peripheral nervous system and co-ordinates the body's responses. Made up of neurons and glial cells, the CNS is the primary area affected by multiple sclerosis (MS).
MS is a chronic autoimmune disease (Ghasemi et al, 2017) that damages nerves in the CNS, leading to various symptoms, depending on the location of the damage. The impact is felt throughout the body, as the peripheral nerves for the face and body are linked to the CNS at the spinal vertebrae.
The pathophysiology of MS involves a complex interplay between the immune system and the CNS (Frischer et al, 2019). In people with MS, the immune system mistakenly attacks and damages the myelin sheath, leading to inflammation and scarring (Compston and Coles, 2008) (Figure 2). This damage can occur in multiple areas of the brain and spinal cord, which is the reason why symptoms of MS can vary widely between individuals (Ghasemi et al, 2017).
In addition to the damage caused by inflammation, researchers have identified oxidative stress as a key contributor to the development of MS (Haider et al, 2014). It occurs when there is an imbalance between the production of reactive oxygen species and the body's ability to neutralise them (Fridovich, 1995). This can lead to cell damage and inflammation in the nervous system, exacerbating the symptoms of MS (Haider et al, 2014).
Because MS is such a variable condition, not all individuals will experience all symptoms, and these can also come and go, or change over time (see Box 3).
Box 3.Common symptoms associated with multiple sclerosis
- Fatigue
- Difficulty walking
- Numbness or tingling
- Muscle weakness
- Spasticity
- Visual disturbances
- Problems with balance and co-ordination
- Bladder and bowel dysfunction
- Cognitive changes
- Emotional changes
- Pain
- Heat sensitivity
Epilepsy
Epilepsy is a neurological condition characterised by recurrent seizures. These are caused by abnormal electrical activity in the brain, which can lead to a range of symptoms such as : convulsions, loss of consciousness, and altered behaviour.
Epilepsy is a complex neurological condition. Specific symptoms can vary widely from person to person, and those outlined in Box 4 are the main symptoms that people may experience. Some individuals' epilepsy may be well-controlled with medication, others may experience frequent or more severe seizures requiring additional treatment strategies.
Box 4.Symptoms related to epilepsy
- Seizures
- Auras, which are warning signs or sensations that precede a seizure
- Loss of consciousness
- Repetitive jerking or twitching movements of the limbs or other body parts
- Unusual sensations, such as tingling, numbness or a feeling of déjà vu
- Confusion, memory loss or difficulty recalling recent events
- Incontinence
- Repetitive movements: automatisms, such as lip smacking, chewing or picking at clothes, may be observed during complex partial seizures
- Postictal state: after a seizure, there is often a period of confusion and fatigue, before the person returns to normal functioning
The pathophysiology of epilepsy involves a disruption in the normal balance of excitation and inhibition in the brain. Normally, there is a delicate balance between excitatory and inhibitory signals, allowing for normal brain function. In people with epilepsy, this balance is disrupted, leading to excessive excitatory activity and seizures.
Researchers have also identified (Patel et al, 2019; Falco-Walter, 2020; Chaunsali et al, 2021) changes in the structure and function of neurons and synapses in the brains of people with epilepsy. These changes can lead to an increase in seizure activity and a decrease in the brain's ability to regulate itself. Several studies (Anwar et al, 2020; Mukhtar, 2020; Balestrini et al, 2021 have investigated the pathophysiology of epilepsy, identifying mechanisms that contribute to the development and recurrence of seizures. One study (Avoli and de Curtis, 2011) found that there is a decreased ability of inhibitory neurons to regulate the activity of excitatory neurons in people who have epilepsy, which leads to an increase in excitatory activity and the occurrence of seizures.
Another study (Barker-Haliski and White, 2015) found that changes in the structure and function of synapses in the brain can contribute to the development of epilepsy. Specifically, the researchers found that there is an increase in the number of excitatory synapses in people with epilepsy, which can lead to an imbalance between excitatory and inhibitory signals and an increased risk of seizures.
A further study (Vezzani et al, 2016) determined that inflammation in the brain can contribute to the development of epilepsy. The researchers found that these inflammatory processes can disrupt the normal balance of excitatory and inhibitory signals, leading to increased excitability and seizure development.
Overall, the studies have suggested the pathophysiology of epilepsy involves a complex interplay between excitatory and inhibitory signals in the brain, as well as changes in the structure and function of neurons and synapses, and inflammation in the brain.
Stroke
Stroke is a neurological condition that occurs when blood flow to the brain is disrupted by a blood clot or bleeding. There are two main types of stroke: ischaemic stroke and haemorrhagic stroke, each of which has a different pathophysiology.
Ischaemic stroke occurs when blood flow to the brain is blocked, which is usually by a blood clot. This blockage prevents oxygen and nutrients from reaching brain cells, leading to cell death and brain damage. The pathophysiology of ischaemic stroke involves a complex interplay between the blood vessels and the brain. When blood flow to the brain is disrupted, a cascade of events occurs that can lead to cell death and brain damage: these include inflammation, oxidative stress and excitotoxicity, when neurons become overstimulated and damaged (Hui et al, 2022; Hill and Mitchell, 2023).
Haemorrhagic stroke occurs when a blood vessel in the brain ruptures, causing bleeding. The pathophysiology of haemorrhagic stroke involves the accumulation of blood in the brain, leading to increased pressure and damage to brain cells. This pressure can also cause brain shift, or the displacement of brain tissue, due to the raised intracranial pressure, causing further damage (Cardim et al, 2021).
Both types of stroke can result in a range of symptoms, such as paralysis, difficulty speaking and cognitive impairment. Treatment options depend on the type and severity of the stroke, but may include medications, rehabilitation and, in some cases, surgery (Cardim et al, 2021).
Time is of the essence in treating stroke, prompt medical attention can minimise damage to the brain and improve the chances of recovery. FAST – which stands for ‘face drooping’, ‘arm weakness’, ‘speech difficult’ and ‘time to call 999’ can help quickly identify whether a person is having a stroke (Box 5) and to get medical help promptly. It is important to remember the acronym ‘FAST’, a simple way to recognise stroke symptoms.
Box 5.FAST
- F Face drooping: ask the person to smile. Does one side of their face droop?
- A Arm weakness: ask the person to raise both arms. Does one arm drift downward?
- S Speech difficulty: ask the person to repeat a simple sentence. Is their speech slurred or strange?
- T Time to call 999: if you observe any of these signs, it is crucial to call emergency services immediately
Case study: Maria Brown, a 65-year-old patient with Parkinson's
Background
Maria Brown, who is 65 years old, has been diagnosed with Parkinson's disease. She has been referred to the neurology clinic for management of symptoms, which include tremors, bradykinesia and rigidity. Ms Brown has a history of hypertension and hyperlipidaemia, for which she takes lisinopril and atorvastatin.
Assessment and diagnosis
On assessment, Ms Brown reports difficulty with her activities of living due to her motor symptoms. She reports difficulty with dressing, grooming and eating, as well as difficulty with balance and falls. The nurse notes a resting tremor in her left hand, as well as bradykinesia and rigidity.
The neurologist confirms the diagnosis of Parkinson's and prescribes a dopamine agonist to help alleviate the symptoms. The neurologist recommends that Ms Brown begins a regular exercise programme and refers her to physiotherapy for assessment and treatment.
Management and treatment
As the registered nurse assigned to Ms Brown's care, your role is to assist with the management of her symptoms, ensuring that she receives safe and effective care. This includes administering her medications as prescribed, monitoring for adverse effects and providing education and support to the patient and her family. You administer her medication, making sure to assess her vital signs before and after administration, as well as monitor for adverse effects such as nausea, dizziness or hallucinations.
You also discuss with Ms Brown the importance of being vigilant about monitoring for potential side-effects associated with dopamine agonists. It is crucial, for example, to explain to the patient how she must be aware of a potential side effect called impulse control disorders (ICDs). Offering Ms Brown insight about ICDs and monitoring for these behaviours is essential for her wellbeing.
The nursing care provided focuses on offering Ms Brown holistic support and maintaining her dignity and quality of life. She is provided with more than simply physical support and the administration of medication. Her care encompasses emotional, psychological and holistic care, enhancing her overall wellbeing.
You also work with the physiotherapist to ensure that Ms Brown is receiving the appropriate exercises and interventions to improve her mobility and balance.
As part of your education and support role, you provide Ms Brown and her family with information about Parkinson's, including its causes, symptoms and treatment options. You also provide her with resources for support groups and other community resources, which can help them cope with the challenges of living with Parkinson's.
Follow-up
As part of follow-up care, you monitor Ms Brown's symptoms, assessing her response to treatment. You also work with the neurologist, adjusting her medication regimen as needed, and provide ongoing education and support to the patient and her family.
Conclusion
Parkinson's disease is a chronic neurological condition that can have a significant impact on a person's quality of life. As a nurse, it is important to provide safe and effective care to patients with Parkinson's, including administering medications, monitoring for adverse effects, and providing education and support to patients and their families.
By working collaboratively with other health professionals and providing ongoing care and support, nurses can help improve the outcomes and quality of life for patients with Parkinson's.
Migraine
Migraine is a neurological disorder characterised by recurrent episodes of headache that can be severe and disabling. The exact cause of migraine is not fully understood, Several studies have identified key changes in the brain that occur during an episode.
One of the hallmarks of migraine is a change in the activity of the trigeminal nerve, a major sensory nerve in the face and head. According to Goadsby et al (2017), during a migraine this nerve becomes overactive, leading to the release of neuropeptides such as calcitonin gene-related peptide (CGRP) and substance P; these activate and sensitise pain receptors. CGRP plays a crucial role in the pathophysiology of migraine because it can dilate blood vessels in the brain, leading to headache and other symptoms. The symptoms that are associated with migraine will vary from person to person. It is important to note that not everyone with migraines experience all the symptoms listed in Box 6.
Box 6.Key symptoms of migraine
- Headaches: severe, throbbing, often located on one side of the head
- Visual disturbances (auras) before the headache phase
- Sensitivity to light (photophobia) during an attack
- Sensitivity to sound (phonophobia)
- Nausea and vomiting
- Pain exacerbated by physical activities
- Sensory symptoms such as tingling or numbness in the face or extremities and difficulty speaking
- Pulsating or throbbing sensation (pain), which can be debilitating
- Aura without headache, individuals may experience an aura without the subsequent headache phase, known as a ‘silent migraine’ or ‘migraine equivalent’
Studies (Ayata, 2018; Dussor, 2019) have identified changes in the activity of certain brain regions during a migraine. For example, the cortex, which is involved in processing sensory information, becomes overexcited during a migraine, leading to sensitivity to light and sound. As per Ayata (2018), functional magnetic resonance imaging (MRI) studies have shown that the cortical spreading depression (CSD) is the underlying cause of the aura in migraine. CSD is a wave of neuronal depolarisation that propagates across the cerebral cortex and is accompanied by increased blood flow and decreased oxygen supply to the brain.
Consequently, while the exact cause of migraine is still unknown, researchers have identified several changes in the brain that occur during an episode, including overactivity of the trigeminal nerve and the overexcitability of certain brain regions such as the cortex. These findings provide insight into the pathophysiology of migraine and may guide the development of new therapeutic approaches.
Amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS) is often referred to as MND (motor neurone disease). It is a neurodegenerative disease that affects motor neurons in the brain and spinal cord, leading to progressive muscle weakness, spasticity and, eventually, paralysis. The pathophysiology of ALS is complex and not yet fully understood, several studies (Ashford et al, 2021; Joshua et al, 2022; Noakes et al, 2023) have identified some key changes occurring in the brain and nervous system of people with the disease.
A hallmark of ALS is the accumulation of abnormal protein deposits (including TDP-43, FUS and SOD1) in the brain and spinal cord. These protein aggregates interfere with the normal functioning of motor neurons, leading to their degeneration and death (Grad et al, 2020).
In addition to the protein changes, researchers (Appel et al, 2021; Ravnik-Glavač et al, 2022; Xiong et al, 2022) have identified inflammation and oxidative stress as key contributors to the development and progression of ALS. Chronic inflammation in the nervous system can lead to the activation of glial cells, producing cytokines and other inflammatory mediators further damaging motor neurons (Raffaele et al, 2020). Oxidative stress can also contribute to motor neuron damage by causing cellular damage and death (Solleiro-Villavicencio and Rivas-Arancibia, 2018).
Research has also shown changes in the structure and function of motor neurons in people with ALS. For instance, researchers have identified defects in axonal transport, the process by which proteins and other cellular materials are transported along the length of a neuron. These defects can lead to the accumulation of toxic materials in motor neurons, leading to their degeneration and death (Grad et al, 2020).
Consequently, the pathophysiology of ALS involves a complex interplay between protein aggregation, inflammation and oxidative stress, as well as changes in the structure and function of motor neurons. Although there is currently no cure for ALS, understanding the underlying pathophysiology of the disease may help researchers to develop new therapeutic strategies to slow or halt its progression.
Box 7 provides an overview of symptoms associated with ALS/MND.
Box 7.Common symptoms associated with amyotrophic lateral sclerosis/motor neurone disease
- Muscle weakness: progressive muscle weakness affecting various muscle groups. Typically starts in one region, ie the hands or legs and spreads over time
- Muscle atrophy: muscles atrophy due to the loss of motor neurons controlling them
- Fasciculations (muscle twitching)
- Dysarthria, weakening of muscles used for speech can lead to slurred speech and difficulty articulating words
- Dysphagia: ALS/MND can affect muscles involved in swallowing
- Respiratory symptoms can impact muscles involved in breathing, leading to shortness of breath and respiratory difficulties
- Fatigue and muscle cramps
- Emotional and cognitive changes, such as depression or anxiety, there may be subtle cognitive changes
- Pseudobulbar affect, uncontrollable emotional outbursts, such as laughing or crying, unrelated to the person's emotional state
Huntington's disease
Huntington's disease is a progressive neurological condition characterised by a range of symptoms, including movement disorders, cognitive impairment and psychiatric symptoms. It is the result of a genetic mutation, which causes the production of a toxic protein called huntingtin that accumulates in the brain and leads to damage to neurons. The onset and progression of Huntington's disease varies among individuals. Box 8 provides insight into the symptoms associated with the condition.
Box 8.Symptoms that may be related to Huntington's
- Uncontrollable, jerky and random movements (chorea)
- Cognitive changes/cognitive decline
- Behavioural and psychiatric symptoms, including mood swings, irritability, aggression, depression, anxiety and social withdrawal
- Physical decline
- Dysphagia
- Weight loss
- Dysarthria
- Impaired eye movements
- Disrupted sleep patterns
- Difficulty concentrating and planning
- Loss of independence
The genetic mutation is dominant, so only one copy of the gene is needed for an individual to develop the condition (National Institute of Neurological Disorders and Stroke, 2023). It means that, if one parent has Huntington's disease, each child has a 50% chance of inheriting the mutated gene and developing the disease. Understanding the dominant nature of the mutation can significantly impact family planning decisions. Potential parents may opt for genetic counselling or consider options such as in vitro fertilisation with pre-implantation genetic diagnosis to avoid passing on the gene.
The pathophysiology of Huntington's disease involves a disruption in the normal functioning of neurons and synapses in the brain. According to Petersén and Björkqvist (2006), the huntingtin protein disrupts the normal transport of molecules within neurons, leading to an accumulation of toxic substances and damage to neurons. The accumulation of huntingtin in neurons also leads to a decrease in the activity of certain enzymes that are important for normal neuronal function, which further contributes to the neuronal damage seen in the disease.
Researchers have also identified changes in the activity of certain brain regions in people with Huntington's disease. The basal ganglia, which is involved in movement control, becomes overactive, leading to the characteristic movement disorders seen in the disease (Mink, 2016). The overactivity of the basal ganglia is thought to be due to the loss of inhibitory neurons that normally regulate the activity of the basal ganglia.
Consequently, the pathophysiology of Huntington's disease involves a disruption in the normal functioning of neurons and synapses in the brain, as well as changes in the activity of certain brain regions, such as the basal ganglia. These findings provide insight into the underlying mechanisms of the disease, and help to guide the development of new therapeutic approaches.
Conclusion
Although the pathophysiology of each neurological condition is unique, there are some commonalities. Inflammation, oxidative stress and protein aggregation are key contributors to the development of many neurological conditions, including epilepsy, stroke, ALS and Huntington's disease. Understanding these underlying mechanisms can help researchers develop more effective treatments for these conditions in the future. In addition, a deeper understanding of the pathophysiology of migraine can help develop targeted therapies for this common neurological condition.
KEY POINTS
- Neurodegenerative and neurological diseases such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis (motor neurone disease) share common elements of disrupted neural communication and structural integrity due to abnormal protein accumulation
- Inflammation is a recurring theme across multiple conditions, such as Alzheimer's and Parkinson's, where it exacerbates disease progression by damaging neurons
- The immune system plays a significant role in conditions such as multiple sclerosis, where it mistakenly attacks parts of the central nervous system, and also contributes to inflammation in other diseases
- Despite advancements in the understanding the pathophysiology of these conditions, many aspects remain unclear, making continued research critical for the development of effective treatments and interventions
CPD reflective questions
- How can your nursing practice adapt to the individual variability in symptom presentation and disease progression commonly seen in neurological conditions such as Alzheimer's and Parkinson's?
- Consider the varied pathophysiology of the neurological disorders discussed in this article. How could your new knowledge enhance your nursing interventions to develop patient care?
- Given the immune system's involvement in certain neurological conditions, how might nurses collaborate with immunologists or other specialists to provide a more holistic approach to patient care?