Neurological Disorders

Alzheimer’s disease

Alzheimer’s disease is a progressive neurological disorder which causes the degeneration and subsequent death of neurons in the brain. It is the most common cause of dementia, a condition characterised by cognitive decline, thus impacting cognitive, behavioural and social skills.

Alzheimer's can often occur 10-20 years before the manifestation of symptoms, however, short-term memory loss is often the first indicator of the disease. Other associated symptoms as the disease worsens include:

• Challenges in planning and/or problem-solving

• Difficulty completing familiar tasks

• Confusion with time or place

• Trouble understanding visual images and spatial relationships

• Decreased or poor judgement

• Changes in mood and/or personality

There are many unknown factors that come into play when it comes to Alzheimer’s. The onset of the disease could be due to genetic, lifestyle or environmental factors, all of which have an impact on the function of certain proteins within the brain. When these proteins cannot function optimally, they disrupt neurons within the brain and release a series of toxins. The damaged neurons eventually lose contact with each other and die.

Currently, researchers are investigating two proteins found within the brain and analysing their connection to the onset of Alzheimer's. These are beta-amyloid proteins and Tau proteins.

When beta-amyloid proteins cluster together, they form larger deposits called amyloid plaques, which seem to have a harmful effect on neurons by damaging cell to cell communication. The deposition of this protein typically spreads from the basal neocortex, making its way through the hippocampus and then reaching the rest of the cortex.

Tau proteins play an integral part in the internal support and transport system of a neuron, carrying nutrients and other essential materials. In patients with Alzheimer's disease, these Tau proteins change shape, reorganizing themselves into structures called neurofibrillary tangles. The spreading of these tangles begins in the transentorhinal and hippocampal regions, and continues to the primary areas of the neocortex. These tangles are able to disrupt the neuron’s transport system, and are toxic to cells at the same time.

While there is no known cure for Alzheimer’s at the moment, there are drugs which can help temporarily with the cognitive symptoms. One such drug is the cholinesterase inhibitor, which works to boost cell to cell communication by preserving acetylcholine, a neurotransmitter that is often depleted due to Alzheimer’s disease. Another drug used to treat Alzheimer’s is memantine. This drug works towards treating and maintaining an alternate brain cell communication network, and can slow the progression of the symptoms of moderate to severe Alzheimer's.

Epilepsy

Epilepsy is a neurological disorder affecting the central nervous system, causing abnormal brain activity. In an epileptic brain, neurons become hyperexcitable and poised to discharge randomly and abnormally. It is the disruption of control mechanisms to prevent this random discharge, or the promotion of neuron firing, that can lead to epilepsy. The abnormality in brain activity is manifested in the form of seizures, of which there are different types that vary in severity. Symptoms of seizures include, but are not limited to:

• Temporary confusion

• Staring spells

• Uncontrollable jerking movements of the arms and legs

• Loss of consciousness or awareness.

Doctors often classify seizures as focal or generalised. These types vary based on where brain abnormality begins. Focal seizures are those in which brain abnormality begins in only one area of the brain. These types of seizures can result in a loss of consciousness, but this is often not the case. Focal seizures that do not result in a loss of consciousness tend to portray themselves through an alteration of emotions or senses. They may also result in involuntary jerking of a body part and spontaneous sensory symptoms such as tingling, dizziness and flashing lights. Focal seizures which do result in a loss of consciousness often appear as though the individual is zoning out of a situation. The individual might stare into space and not respond normally to their environment, or perform repetitive movements, such as hand rubbing, chewing, swallowing or walking in circles.

Generalised seizures are those that have an effect on all areas of the brain. There are six further types of generalised seizures:

• Absence seizures - often occur in children and are characterized by subtle body movements, eg. lip-smacking and staring into space. These types of seizures might occur in clusters and cause a brief loss of awareness.

• Tonic seizures - cause muscle stiffening, usually in the back, arm and leg muscle.

• Atonic seizures - cause a loss of muscle control, leading to a sudden collapse to the ground.

• Clonic seizures - cause repeated or rhythmic muscle movements, usually affecting the neck, face and arms.

• Myoclonic seizures - usually appear as brief and sudden jerks of the arms and legs.

• Tonic-clonic seizures - cause a sudden loss of consciousness, body shaking and a loss of bladder control.

Treatment for epilepsy relies on anti-seizure medications, which greatly decrease the number of seizures that an individual might experience. These medications are proven to work very well, however, they can cause severe side effects, such as loss of coordination and problems with speech. Hence, it is necessary to actively monitor the individual’s response to these medications and ensure that taking them does not cause more harm than good.

Multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disease that affects the brain and spinal cord. The disease occurs when the insulating layer surrounding nerve fibres (myelin sheath) is attacked by the immune system. The absence of myelin sheath causes messages to be slowed or blocked during transmission, thus leading to difficulty transmitting messages between the brain and other parts of the body. Eventually, this can lead to permanent nerve damage and deterioration, hence MS can potentially be disabling.

The symptoms of MS vary depending on the extent and severity of nerve damage. These can include the following:

• Limb numbness/weakness, usually occurring on one side of the body

• Electric-shock sensations with some neck movements, eg. bending the neck forward (Lhermitte sign)

• Tremor and/or lack of coordination

• Partial or complete loss of vision, usually one eye at a time

• Pain with eye movement

• Blurred vision

• Prolonged double vision

• Slurred speech

• Fatigue

• Dizziness

• Tingling sensation/pain in parts of the body

• Muscle stiffness and spasms

• Problems with bladder control

The causes of MS are yet unknown, with a combination of genetic and environmental factors believed to be responsible. Some risk factors that increase the likelihood of individuals developing the disease are as follows:

• Age - onset usually occurs between the ages of 20 and 40

• Sex - women are 2-3 times more likely to have relapsing-remitting MS than men

• Family history - higher risk if parent(s) or sibling(s) have had the disease

• Infections - several viruses have been associated with a higher risk of MS, eg. Epstein-Barr virus, which causes infectious mononucleosis

• Vitamin D - low levels of vitamin D and sunlight exposure are associated with a higher risk of MS

• Autoimmune diseases - higher risk of MS with certain autoimmune diseases, eg. thyroid disease, pernicious anemia, psoriasis, type 1 diabetes or IBD.

As for the prognosis of the disease, most people have a relapsing-remitting course of disease, with periods of new symptoms over days or weeks, followed by periods of disease remission lasting from months to even years. There are two types of disease progression - primary-progressive MS, and secondary-progressive MS. Secondary-progressive MS is more common, occuring in over 50% of patients, where steady progression of symptoms occurs with or without periods of remission, within 10 to 20 years from the period of disease onset. Primary-progressive MS, characterised by a gradual onset and progression of symptoms, usually without relapses, is relatively less common amongst patients.

There is no cure for MS till date, however, medications and rehabilitation strategies can be used for management. Some of the medications that can be used to treat MS relapses and modify the disease course include:

• Injectable medications - eg. avonex (delays the time to the next attack), copaxone (blocks myelin-damaging T-cells, mechanism still unknown) and Kesimpta (monoclonal antibody that binds to some immune B cells and depletes them to prevent them destroying myelin sheath)

• Oral medications - eg. aubagio (inhibits the function of certain immune cells active in MS), dimethyl fumarate (causes the immune response to be less inflammatory and is thought to have antioxidant properties that protect the brain and spinal cord from damage) and mavenclad (temporarily reduces the number of T and B lymphocytes without suppressing the immune system continually)

• Infused medications - eg. tysabri (monoclonal antibody that prevents the movement of potentially damaging immune cells from the bloodstream) and ocrevus (monoclonal antibody that targets CD20 positive B lymphocytes, which contribute to nerve damage in MS).

The various methods of rehabilitation that can be used to manage MS include:

• Physical therapy - patients can seek help from physical therapists to improve mobility, strength, balance, posture, fatigue and pain.

• Occupational therapy - patients can also consult occupational therapists, who provide training in energy conservation techniques and guidance on how to use adaptive tools and devices to simplify everyday tasks.

• Vocational rehabilitation - there may be state vocational rehabilitation programs available for patients to help them maintain current employment or find new employment to accommodate their needs.

• Speech-language pathology - a speech-language pathologist can be consulted to treat problems with speech and swallowing, which could result due to extensive damage to the nervous system.

• Cognitive rehabilitation - patients can consult neuropsychologists to treat changes in their ability to think, reason, concentrate or remember.

Parkinson’s disease

Parkinson’s disease is a progressive nervous system disorder which affects one’s movement. The disorder is both degenerative and progressive, meaning that the onset of symptoms is gradual, and these symptoms worsen over time.

Parkinson's occurs when neurons in the motor cortex, mainly the basal ganglia and substantia nigra, become impaired and die. As the neurons in these areas are associated with dopamine production, Parkinson’s causes a drastic reduction in dopamine production, which could be why Parkinson’s patients experience issues with movement. Patients suffering from Parkinson's also lose nerve endings that are responsible for secreting norepinephrine. Norepinephrine acts as the chemical messenger of the sympathetic nervous system, which is responsible for the body’s rapid involuntary responses, such as the control of heart rate and blood pressure. The loss of norepinephrine might explain the fatigue and irregular blood pressure associated with Parkinson’s.

Some cases of Parkinson’s are hereditary, while others can be traced to genetic mutations. However, the majority of cases occur randomly and do not run in families. This has led many researchers to believe that the onset of Parkinson’s is influenced by a combination of environmental and genetic factors.

The symptoms of Parkinson’s include, but are not limited to, the following:

• A tremor in hands, arms, legs, jaw or head

• Stiffness of the limbs and trunk

• Slowness of movement (bradykinesia)

• Irregular blood pressure

• Fatigue

Symptoms tend to originate in one side of the body, eventually affecting both sides as the disease progresses. It is likely that symptoms will still be more serious on their side of origin.

Parkinson’s can be diagnosed on the basis of an individual’s medical history and a neurological examination. Various biochemical tests can be used to diagnose cases with genetic origins. As of yet, there is no cure for the disease, however, several medications and rehabilitative therapies can be administered to manage the symptoms.

References

• Alzheimer’s disease. Available at: https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/symptoms-causes/syc-20350447#:~:text=Alzheimer's%20disease%20is%20a%20progressive,person's%20ability%20to%20function%20independently (Accessed: 8 September 2020)

• 10 Early Signs and Symptoms of Alzheimer's (2020). Available at: https://www.alz.org/alzheimers-dementia/10_signs (Accessed: 28 November 2020).

• Raskin et al. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384474/ (Accessed: 8 September 2020)

• Alzheimer’s disease - Diagnosis and Treatments. Available at: https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/diagnosis-treatment/drc-20350453 (Accessed: 8 September 2020)

• Epilepsy. Available at: https://www.mayoclinic.org/diseases-conditions/epilepsy/symptoms-causes/syc-20350093#:~:text=Epilepsy%20is%20a%20central%20nervous,races%2C%20ethnic%20backgrounds%20and%20ages (Accessed: 8 September 2020)

• Scharfman. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2492886/ (Accessed: 8 September 2020)

• Epilepsy - Diagnosis and Treatments. Available at: https://www.mayoclinic.org/diseases-conditions/epilepsy/diagnosis-treatment/drc-20350098 (Accessed: 8 September 2020)

• Medications (2020). Available at: https://www.nationalmssociety.org/Treating-MS/Medications (Accessed: 7 September 2020).

• Multiple sclerosis - Symptoms and causes (2020). Available at: https://www.mayoclinic.org/diseases-conditions/multiple-sclerosis/symptoms-causes/syc-20350269 (Accessed: 7 September 2020).

• Rehabilitation (2020). Available at: https://www.nationalmssociety.org/Treating-MS/Rehabilitation (Accessed: 7 September 2020).

• Avonex (2020). Available at: https://www.nationalmssociety.org/Treating-MS/Medications/Avonex (Accessed: 7 September 2020).

• Multiple sclerosis (2017). Available at: https://www.nhs.uk/conditions/multiple-sclerosis/ (Accessed: 7 September 2020).

• Kesimpta (2020). Available at: https://www.nationalmssociety.org/Treating-MS/Medications/Kesimpta (Accessed: 7 September 2020).

• Aubagio (2020). Available at: https://www.nationalmssociety.org/Treating-MS/Medications/Aubagio (Accessed: 7 September 2020).

• Tysabri (2020). Available at: https://www.nationalmssociety.org/Treating-MS/Medications/Tysabri-%C2%AE (Accessed: 7 September 2020).

• Ocrevus (2020). Available at: https://www.nationalmssociety.org/Treating-MS/Medications/Ocrevus (Accessed: 7 September 2020).

• Mavenclad (2020). Available at: https://www.nationalmssociety.org/Treating-MS/Medications/Mavenclad (Accessed: 7 September 2020).

• Dimethyl Fumarate Delayed-Release Capsules (2020). Available at: https://www.nationalmssociety.org/Treating-MS/Medications/Dimethyl-Fumarate-Delayed-Release-Capsules (Accessed: 7 September 2020).

• Parkinson's disease - Symptoms and causes (2020). Available at: https://www.mayoclinic.org/diseases-conditions/parkinsons-disease/symptoms-causes/syc-20376055 (Accessed: 7 September 2020).

• Parkinson's Disease (2020). Available at: https://www.nia.nih.gov/health/parkinsons-disease#:~:text=Parkinson's%20disease%20is%20a%20brain,have%20difficulty%20walking%20and%20talking. (Accessed: 7 September 2020).

• What Is Parkinson's? (2020). Available at: https://www.parkinson.org/understanding-parkinsons/what-is-parkinsons (Accessed: 11 September 2020).

• Spine, M. (2020) Parkinson's Disease (PD) Mayfield Brain & Spine Cincinnati, Ohio, Mayfieldclinic.com. Available at: http://www.mayfieldclinic.com/pe-pd.htm#:~:text=Parkinson's%20disease%20(PD)%20is%20a%20degenerative%2C%20progressive%20disorder%20that,plan%20and%20control%20body%20movement. (Accessed: 11 September 2020).