GEP (Life Control) Week 4 Flashcards

Question

What is the epidemiology and aetiology of parkinson

Answer 1

**Epidemiology:** * The mean age of onset of PD is about 65 years -Cases occurring in people aged 21-40 years are considered young-onset PD -Patients younger than 21 years have juvenile parkinsonism * PD affects 1 to 2 people per 1000 at any time * The prevalence increases with age to affect 1% of the population above 60 years * PD is more common in men than women **Aetiology:** * The aetiology of PD is unknown * There is a genetic predisposition, with subsequent environmental factors/exposures contributing to the evolution of clinical disease * Age is the only undisputed risk factor

Answer 2

**Cardinal motor features:** Bradykinesia Pill rolling tremor (4-6Hz) Rigidity Asymmetric onset **Other motor features:** Hypokinetic dysarthria Hypophonia Shuffling gait Stooped posture Poor balance Micrographia Mask like face **Non-motor features** Constipation Hyposmia Sleep disorders fatigue **Neuropsychiatric features**: Anxiety Depression Impulsive-compulsive behaviour Psychosis Cognitive impairment Dementia

Answer 3

Parkinson's disease is characterized by: * Progressive degeneration of dopamine-producing neurons in the substantia nigra pars compacta * Leading to dopamine deficiency in the basal ganglia -Loss of dopamine to 20-40% of normal before symptoms are seen * This disruption of dopamine signaling results in abnormalities in motor control and other brain functions -Reduced excitation of the direct pathway = reduced disinhibition of the thalamus = reduced movement -Reduced inhibition of the indirect pathway = more inhibition of the thalamus = reduced movement **Investigations:** * Diagnosis of Parkinson's disease is primarily based on clinical assessment, including a detailed medical history and neurological examination * One of the best ways of establishing a diagnosis of PD in a patient with suggestive symptoms is a clear response to Levodopa treatment ## Footnote Pathophysiology: Surviving neurons often contain Lewy bodies (made of α-synuclein protein that has misfolded and aggregated) Lewy bodies can be widespread throughout the brain which causes neuronal degeneration and dementia 20-40% of PD patients develop Parkinson’s disease dementia (PDD), usually 10-15 years after diagnosis The primary aetiology appears to be the accumulation of alpha-synuclein in various parts of the brain, primarily the substantia nigra, leading to degeneration and subsequent loss of dopamine in the basal ganglia that control muscle tone and movement. The accumulation of the alpha-synuclein protein may be secondary to a genetic predisposition, such as with the PARK-1 mutation. There has been some recent interest in establishing an infectious etiology that triggers this alpha-synuclein accumulation after reports that the earliest degenerative change in PD appears in the myenteric plexus on the GIT, from where it progresses up to involve the dorsal motor nucleus of the vagus nerve, the sleep centers in the pons, and then the midbrain. This interesting theory also addresses why patients with PD typically suffer from gastrointestinal motility issues and REM sleep disorder, both of which can precede the motor manifestations of PD for many years. Therefore, as our knowledge about the etiology of PD evolves, it is not enough to regard this disorder as primarily caused by a lack of dopamine in the substantia nigra. There appears to be a darker, more extensive pathophysiology behind this, and the non-genetic causes of alpha-synuclein deposition in the brain are a subject of active research. Investigations: MRI is useful in narrowing the differential and excluding other conditions that may present with a similar examination, such as normal pressure hydrocephalus or subcortical stroke. In certain situations, a DAT scan may be used to identify the loss of dopaminergic uptake in the basal ganglia. However, the interpretation of this test can be challenging, and the routine use of this test is to be discouraged. LP can be done to rule out normal pressure hydrocephalus.

Answer 4

-Dopamine involved in control of BG -Important role in motor function, reward-based learning, addiction and mood -Synthesized in substantia nigra of midbrain, starts off with tyrosine, converted into L-DOPA (via TH) and then DA (via DDC), then packaged into vesicles and released into synaptic cleft, where has action in it’s receptors, then taken up into either presynaptic terminal or astrocytes, and broken into inactive metabolites by MAO-B of COMT -Important to know about enzymes in above, as target for some of PD drugs -Dopamine receptors are GPC receptors – 5 types (D1-D5) D1-like (D1 and D5) are ‘S’ coupled, stimulatory, excitatory and depolarize neurons D2-like (D2, D3, D4) are ‘I’ coupled, so inhibitory, so hyperpolarize neurons

Answer 5

Primary mgmt: carbidopa (peripheral DOPA decarboxylase inhibitors) + levodopa (synthetic dopamine precursor) Secondary mgmt: pramipexole OR ropinirole OR rotigotine transdermal (dopamine receptor agonists) Tertiary mgmt: selegiline OR rasagiline OR safinamide (MAO-B inhibitors) Varying the pharmacokinetics of levodopa has sometimes helped, such as newer formulations of delayed-release levodopa or a continuous GI pump infusion form of levodopa

Answer 6

**Physical/non-pharmacological:** Exercise!!! Physiotherapy Occupational therapy Speech and language therapy Psychologists **Other:** Deep brain stimulation ## Footnote Physical/non-pharmacological: Progressive resistance exercise, aerobic exercise, and balance training have been shown to reduce motor symptoms and improve functional status. Activities such as Tai Chi, dance, and music therapy have also been shown to be safe and beneficial for patients with PD, and may improve quality of life and reduce falls. Water-based therapy has shown benefits in improving balance, mobility, and quality of life in people with PD, and may be preferred to land-based therapy by patients with fear of falling. Gait-specific training, rather than generic exercise programmes, should be employed if improved gait performance is the specific outcome of interest. Specific physiotherapy programmes aimed at improving freezing of gait in PD, such as Lee Silverman Voice Treatment-BIG therapy (LSVT-BIG), have been shown to be effective in reducing motor impairments. External cueing (external temporal or spatial stimuli, including rhythmic auditory cues, visual cues,verbal cues, or attentional cues) during physiotherapy reduces motor disease severity and improves gait outcomes. Community-based exercise programmes, which may include a home exercise component, are recommended. These reduce motor disease severity and improve non-motor symptoms, functional outcomes, and quality of life. Virtual reality interventions may be effective for improving balance, motor function, gait, quality of life, and ability to perform activities of daily living in patients with PD, although the evidence is mostly of low quality. Individually tailored and standard cognitive training may improve memory, executive function, and attention in people with PD. Similarly, cognitive rehabilitation has been reported to lead to improvements in one or more cognitive domains Other: Deep brain stimulation has become the surgical procedure of choice as it does not damage brain tissue, is reversible, and the stimulation can be altered as the disease progresses. DBS involves stimulation of the STN, globus pallidus interna, and the thalamus. However, DBS is not complication-free; it is prohibitively expensive, and its long-term benefits remain debatable.

Answer 7

**Prognosis:** * Treatment of PD is symptomatic as no curative or disease-modifying agents are available * Rates of progression vary between patients, with rapidly and slowly progressive forms * A typical course for the slowly progressive form: -2-3 years when treatment with dopaminergic agents improves symptoms -After 5 years of levodopa treatment, motor complications develop -Eventually, after a number of years, symptoms of freezing, falling, and dementia, which do not respond to levodopa, cause significant disability * Factors that predict more rapid rate of progression: -Older age at symptom onset -Rigidity/hypokinesia as presenting symptoms (versus rest tremor) -Associated comorbidities -Decreased response to dopaminergic medications **Complications:** Levadopa induced dyskinesia Dementia Bladder dysfunction Orthostatic hypotension Sleep disorders Dysphagia Psychosis Depression Anxiety ## Footnote Dyskinesias are involuntary, erratic, writhing movements of the face, arms, legs or trunk.

GEP (Life Control) Week 4 Flashcards

(31 cards)