Parkinsonism: Pathophysiology and Clinical Manifestations

by Roy Strowd, MD

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    00:01 Pathophysiologically, what's going on in the brain is the development and deposition of alpha synuclein.

    00:07 So idiopathic Parkinson's disease is an alpha synucleinopathy.

    00:12 And when we think about Parkinsonism, Parkinsonisms and Parkinsonian conditions, we have some that are synucleinopathy and some that are tauopathies.

    00:20 Let's spend a few minutes thinking about the synucleinopathies.

    00:25 Alpha synuclein is a neuronal protein that regulates synaptic vesicle trafficking, and neurotransmitter release.

    00:33 Alpha synuclein is mainly localized at the presynaptic terminals of the neurons, but it's also present in other subcellular compartments, in the cytoplasm and the Golgi complex.

    00:46 In the alpha-synucleinopathies we have build up of alpha synuclein.

    00:50 This starts in the neuronal cytoplasm, where unfolded monomers of alpha synuclein interact and aggregate together to form unstable dimers and oligomers interact even further to form amyloid fibrils, and you can see a depiction of those fibrils here developing and gumming up normal neural circuitry in the brain.

    01:12 Further accumulation of these fibrils results in the development of a Lewy body.

    01:17 And a lewy body is is an abnormal aggregated protein that disrupts normal neural function.

    01:25 Pathophysiologically, why is alpha-synuclein buildup so bad? Well, there's two things I want you to think about that alpha-synuclein does.

    01:34 And the first is it builds up in neurons and we see abnormal neural activity as a result of this byproduct waste product that is accumulated within the neuron.

    01:44 In addition, we also see microglial activation.

    01:48 And this is the immune mediator within the brain, the microglia and this activation of microglia contributes to ongoing damage that occurs in the neurons and other structures within the brain.

    02:00 And the result is neurodegeneration, progressive neurologic dysfunction, decline, and ultimately atrophy and loss of key neural structures in these conditions.

    02:13 So let's think a little bit more about what's happening on a global scale within the brain in this alpha-synucleinopathy and other Parkinsonisms.

    02:21 We categorize this condition as an extrapyramidal disorder.

    02:25 And if we think back to the pyramidal and extrapyramidal systems, they're different.

    02:29 They're different in terms of where they are, and in terms of what patients present with.

    02:34 The extrapyramidal system is the basal ganglia system.

    02:38 It's the caudate, putamen, globus pallidus internus, externus, the subthalamic nucleus and the substantia nigra.

    02:46 And together that circuitry makes up the extrapyramidal system.

    02:50 Problems with the extrapyramidal system present as Parkinsonisms with bradykinesia, rigidity, postural instability, with or without tremor.

    03:00 That contrast a pyramidal system dysfunction.

    03:03 The pyramidal system is the upper motor neuron system.

    03:06 It's the corticospinal and corticobulbar fibers and dysfunction of the pyramidal system presents with weakness and spasticity and increased tone and hyperreflexia.

    03:16 So disorders are very separate in terms of those that affect the extrapyramidal system and the pyramidal system, both in how they present and how we manage those patients.

    03:26 So let's look a little bit closer at the key clinical manifestations of a Parkinsonism.

    03:30 We're going to start with bradykinesia, which means reduced movement.

    03:34 There's less movement, smaller movements, an overall reduction in the amount of movement of the patient.

    03:40 This is seen in 80% of idiopathic PD patients.

    03:44 Patients will have decreased manual dexterity of the fingers and we may see reduced finger tapping or opening and closing of the hands.

    03:52 This progresses from distally often to proximally, and we'll see less movement of the entire body.

    03:57 shuffling of gait can be seen reduced arm swing can be seen.

    04:02 Patients will describe difficulty in completing simple tasks such as tying shoelaces, buttoning clothes, picking up small objects, all of their movements will be slowed and small.

    04:13 And one of the things we look at is the gait.

    04:14 And shuffling of gait is one manifestation of bradykinesia or reduced movement.

    04:22 Let's talk a little bit about the second cardinal feature - rigidity.

    04:25 And this is really important seen in 70 to 80% of patients with idiopathic Parkinson's disease.

    04:32 It's described as increased resistance to passive movements.

    04:35 So when we evaluate rigidity, we have the patient relax.

    04:39 We're looking at passive movement so we're moving the patient's joint as opposed to the patient moving volitionally And we have increase in tone.

    04:48 Importantly, rigidity and parkinsonism are different from the spasticity we see from stroke patients.

    04:54 spasticity is a pyramidal system, it is velocity and angle dependent.

    04:59 There's more resistance out on extension and more resistance, the faster the arm or leg or limb removed.

    05:05 Rigidity is not clasp-knife spasticity.

    05:08 It has lead-pipe rigidity.

    05:10 And so patients who have rigidity or an extrapyramidal symptom have increase in tone throughout the range of movement and with any ankle or velocity, so it's not velocity or ankle dependent.

    05:23 This begins often unilaterally, particularly in patients with idiopathic Parkinson's disease and can progress to the contralateral side, or in some patients, remaining asymmetric throughout the course of the disease.

    05:35 And in some patients, particularly those with idiopathic Parkinson's disease, we can see cogwheel rigidity.

    05:42 cogwheel rigidity is that combination of rigidity plus tremor.

    05:45 Patients are very stiff, there's increased tone to passive movement and on top of that, we have a tremor.

    05:51 And the result is cog wheeling, or that resistance and relaxation of passive movement at the same time.

    05:58 Postural instability is important.

    06:01 This is one of the most important of those initial three cardinal symptoms of a Parkinsonism.

    06:06 It usually occurs in more advanced stages of idiopathic Parkinson's disease, and this is defined clinically using the pull test.

    06:13 The patient is standing upright, the examiner stands behind the patient.

    06:17 And without the patient looking or being aware, the examiner will pull back the patient, pull back on their shoulders and the patient is instructed to remain still.

    06:27 The patient's, on a normal exam is for the patient to remain upright.

    06:32 And an abnormal exam is for the patient to take multiple steps backwards, or to fall as a result of the inability to right oneself using their axial musculature.

    06:43 And then the last cardinal feature is tremor.

    06:46 This is not seen in all parkinsonisms, but is primarily seen in idiopathic Parkinson's disease.

    06:52 The tremor we see in idiopathic Parkinson's Disease is a rest tremor and often described as a pill rolling tremor, with the appearance of the patient rolling a pill in between their thumb and index finger.

    07:05 This is intermittent early in the stages of idiopathic.

    07:09 It decreases with voluntary actions, so when patients are moving, we don't see the tremor, and when their limbs remain at rest, it is more obvious.

    07:17 It can involve the hands often initially or even the legs, lips, jaw and tongue.

    07:22 And initially in idiopathic Parkinson's disease, it's often unilateral, but can progress to bilateral involvement.

    07:28 And importantly, these four cardinal features can be seen in any Parkinsonism.

    07:33 With classic Parkinsonisms, we see rigidity, bradykinesia, postural instability.

    07:38 In idiopathic PD, we often also see tremor.

    09:20 And now let's look at a video of an example of the pull test being performed.

    09:26 And here we're going to see the patient standing upright.

    09:29 The examiner is placed behind the patient and instructs them to remain upright.

    09:34 A pole or force is exerted on the patient's shoulders, and the patient is instructed to stay upright.

    09:40 A normal finding is a patient remaining upright or taking one step.

    09:44 And patients who take multiple steps or may fall have a reduction in axial tone, which is indicative of Parkinsonism.

    09:53 Now let's look at a video of tremor.

    09:55 There are a number of different types of tremor that we can see.

    09:59 Two of the most common types of tremor are rest and action or which what is called a kinetic tremor.

    10:05 The rest tremor that we see is present at rest when the arms are still or the legs are still And often will induce this by asking the patients to rest their arms and legs and ask them to recite the days of the week or the months of the year forward or backward distracting them to bring out that rest tremor.

    10:23 That's different from a kinetic or action tremor which is present with action To evaluate action or kinetic tremors, we'll have the patient draw a series of spirals and action movement and we're looking for the presence of that tremor during action movement.

    About the Lecture

    The lecture Parkinsonism: Pathophysiology and Clinical Manifestations by Roy Strowd, MD is from the course Introduction to Parkinson Disease.

    Included Quiz Questions

    1. Cogwheel rigidity
    2. Clasp-knife rigidity
    3. Spastic rigidity
    4. Clonus
    5. Bradykinesia
    1. Lewy bodies
    2. Amyloid plaques
    3. Neurofibrillary tangles
    4. Pick bodies
    5. Kuru plaques
    1. Parkinsonism
    2. Spasticity
    3. Creutzfeldt-Jakob disease
    4. Essential tremor
    5. Alzheimer dementia
    1. Bradykinesia
    2. Rigidity
    3. Postural instability
    4. Resting tremor
    5. Vocal tremor

    Author of lecture Parkinsonism: Pathophysiology and Clinical Manifestations

     Roy Strowd, MD

    Roy Strowd, MD

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