Movement Disorders (1) Flashcards
Movement disorders are among the most fascinating disorders within the realm of neurology. They do not involve paralysis of movement but rather distortions or perversions of movements and span a spectrum from disorders that produce excessive movement to disorders that result in a paucity of movement.
Movement disorders are the result of dysfunction or damage to the portions of the brain that are collectively referred to as ____ _______
the basal ganglia.
What are the basal ganglia nuclei?
The nuclei that are generally considered to comprise the basal ganglia are the caudate, putamen, globus pallidus, subthalamic nucleus, and the substantia nigra.
What is the main function of the basal ganglia?
The basic function of the basal ganglia is not to produce or initiate movement – that is the function of the pyramidal system – but to modulate movement. In so doing, the basal ganglia work to facilitate intended movements while suppressing unwanted movements.
Disease processes that damage the basal ganglia, then, will produce a clinical picture of either too little movement or excessive, unwanted movement. Disorders that result in too little movement are labeled what?
hypokinetic movement disorders, while disorders that produce excessive, or unwanted or distorted movement are referred to as hyperkinetic movement disorders.
Some movement disorders damage the basal ganglia in such a way that elements of both too little and distorted movement may be present. These are called what?
mixed movement disorders.
Three of the most frequently encountered hypokinetic movement disorders are:
Parkinson’s disease,
progressive supranuclear palsy, and
multiple system atrophy.
How common is PD?
Parkinson’s disease (PD) is a relatively common neurologic disease. It is the second-most common neurodegenerative disorder, after Alzheimer’s disease.
If one looks at the entire population, PD may not seem so common, with a prevalence of only 100 per 100,000 (1 per thousand). However, it is an age-related disorder, so that if one looks at individuals age 60 and above, a very different picture emerges. In this elderly population, the prevalence of PD is approximately 2000 per 100,000 - or 2% of this age group, and some figures place this prevalence even higher.
What causes PD?
The etiology of PD is not known and, indeed, there may not be a single uniform etiology for everyone with the disorder. For a relatively small proportion of individuals with PD, specific genetic mutations have been identified and it is probable that more will be identified in the future.
In individuals with young-onset PD, where PD symptoms appear before age 50, genetic factors are more likely to be operative than in persons who develop PD later in life. In these individuals, who actually make up the majority for PD patients, other factors appear to be important. A number of environmental factors have been suggested to be involved in the genesis of PD, but none have been unequivocally proven.
The typical age of onset of PD motor symptoms is when?
between the ages of 55-65. Approximately 10% of individuals develop their first symptoms before age 40. With current PD treatment, the life expectancy of someone with PD is almost, though not quite, normal.
How does PD present initially?
The motor features of PD typically first involve one side of the body, but eventually become bilateral. The initial asymmetry of dysfunction, however, is often maintained.
PD is characterized by four primary, or cardinal, motor features. Namely:
Tremor, typically appearing with the limb at rest and disappearing with movement, is the most frequent initial motor feature of PD.
Rigidity: characterized by increased muscle tone that is persistently present throughout passive movement (unlike the “clasp-knife” pattern of increased tone evident with spasticity).
The term bradykinesia literally means slow movement, but the concept of bradykinesia actually involves much more – it includes difficulty both initiating and terminating movement, slowness in carrying out movement, difficulty performing repetitive movements, and difficulty carrying out simultaneous movements.
Postural instability
Postural instability, or balance impairment, is a cardinal feature of PD but is different from the other cardinal features. How?
In that it does not appear early in the course of PD, but makes its appearance later in the course of the disease.
In fact, if an individual with parkinsonism develops balance impairment and falling within the first year of the appearance of motor dysfunction, he or she almost certainly does not have idiopathic PD but rather one of the other parkinsonian syndromes, such as progressive supranuclear palsy or multiple system atrophy.
There are a number of additional motor features of PD that are very characteristic of the disorder, but are not referred to as cardinal features. Namely:
Reduced facial expression, or facial masking, is often present and magnified by reduced frequency of blinking.
The posture of the person with PD gradually becomes more stooped.
Gait changes also develop in which the PD patient walks with smaller steps, although still on a narrow base, and doesn’t pick up one or both feet normally, which results in a shuffling character to the gait.
Reduced arm swinging when walking is also characteristic.
Speech becomes softer and often somewhat slurred – the term hypokinetic dysarthria is applied to this characteristic PD speech pattern.
Handwriting may become progressively smaller in size – sometimes a pattern will be evident in which the handwriting starts out virtually normal in size, but becomes progressively smaller the longer the individual writes (aka micrographia)
This slide gives a sense of the facial masking characteristic of PD
This slide demonstrates the stooped posture characteristic of PD
PD is also characterized by a number of features that have nothing to do with motor function. These are called what?
non-motor features.
Behavioral changes are probably the most widely recognized non-motor features of PD. What are some common ones?
Depression occurs in 40-50% of PD patients at some point during the course of their illness, and may actually precede the development of motor features.
Anxiety may develop in up to 40% of individuals also.
Progressive cognitive impairment may become evident as PD progresses. However, if it develops early in the course of an individual with parkinsonism, the diagnosis is probably not idiopathic PD but rather one of the other “parkinsonism-plus” syndromes such as dementia with Lewy bodies.
Cognitive impairment
Describe the cognitive impairment seen in PD
Characterized by executive dysfunction, in which individuals experience difficulty making decisions and carrying out plans, rather than the more pure memory impairment characteristic of Alzheimer’s disease.
Autonomic dysfunction is another non-motor facet of PD. Virtually all aspects of autonomic function may be affected. Describe some.
Gastrointestinal dysfunction in the form of constipation is most widely recognized, but dysphagia and impaired gastric emptying may also be present.
Bladder dysfunction most often takes the form of bladder over-activity with frequency and urgency, but underactive bladder function, with impaired bladder emptying, may be present in some patients.
Erectile dysfunction is common in men with PD and diminished libido in both men and women.
Impaired blood pressure regulation, with orthostatic hypotension is often attributed to PD medications, but can occur as part of PD itself.
Cardiac sympathetic denervation is also evident in many patients with PD, but doesn’t produce clear-cut symptoms.
Individuals with PD may display thermoregulatory dysfunction in the form of episodic profuse sweating, which is embarrassing and aggravating but not dangerous.
Non-motor dysfunction in PD may also entail a variety of other features. What are some?
Impairment of olfaction may become evident years before the classic motor features of PD make their appearance.
Blurred vision, particularly for near tasks, is frequently described by PD patients. Pain is also common in the setting of PD. In fact, shoulder discomfort, often misdiagnosed as bursitis, may be the presenting symptom of PD.
Individuals with PD may also display a number of sleep-related problems. Like what?
Sleep fragmentation, with frequent awakenings, is very common.
The most characteristic sleep-related problem of PD, however, is the development of REM sleep behavior disorder, in which individuals retain the ability to move during dreaming and, thus, may “act out” their dreams with hitting, kicking, hollering, and even jumping out of bed.
Fatigue is yet another very frequent non-motor feature of PD that is poorly understood.
Although the pathologic process that constitutes PD is clearly more complicated and widespread, the primary basis of the motor dysfunction of PD – and the classic pathologic abnormality of PD – is what?
degeneration of pigmented neurons that have their cell body in the substantia nigra pars compacta in the midbrain. Neurons in other brainstem nuclei, such as the locus ceruleus and the dorsal motor nucleus of the vagus, are also affected.
Below: This slide demonstrates the loss of pigmentation in the substantia nigra in PD.
Microscopically, the pathological hallmark of PD is the presence of what?
cytoplasmic inclusion bodies, called Lewy bodies, within surviving pigmented neurons within the substantia nigra and elsewhere. Lewy bodies are also present within the enteric nervous system, although here they are not within pigmented neurons.
Below: The fried egg-appearing inclusion within the cytoplasm of this pigmented neuron is a Lewy body.
A primary component of Lewy bodies is a protein called ________
alpha-synuclein. Thus, disease processes in which alpha-synuclein aggregates are labelled synucleinopathies.
The neurochemical hallmark of PD is ______ deficiency, classically within the substantia nigra in the midbrain and the striatum within the cerebrum.
dopamine. This is the result of the degeneration and death of the pigmented neurons with their cell bodies in the substantia nigra and their axons terminating within the striatum, which utilize dopamine as their neurotransmitter. Dopamine neuronal loss, however, is not confined to the substantia nigra and involves dopaminergic neurons in other locations as well.
It has also become clear that the neurochemical disturbances in PD do not involve dopaminergic neurons exclusively. In fact, multiple other neurotransmitter systems are also involved. What are some?
Nor, Serotonin, glutamate, others
What is Progressive supranuclear palsy (PSP)?
Characterized by features of parkinsonism, but also by additional features not seen in PD. Therefore it is classified as a “parkinsonism-plus” syndrome.
How common is PSP? Prognosis?
PSP is much less common than PD. Reports of prevalence range from approximately 1.0-6.5 per 100,000. No genetic basis for PSP has been uncovered. Its usual age of onset is somewhat younger than that of PD, typically between the ages of 50-60. In contrast to PD, there is no effective treatment for the symptoms of PSP and it follows a relentlessly progressive course with a life expectancy of only approximately 10 years.
What are the neruologic features of PSP?
The parkinsonian features of PSP consist primarily of rigidity and bradykinesia. Unlike PD, the features of PSP are often quite symmetric. Axial musculature is especially likely to be involved and this may sometimes result in neck extension (in contrast to the neck flexion of PD), although neck extension is not present in the majority of individuals with PSP.
Individuals with PSP may display facial masking in the form of a peculiar “astonished” facial expression that differs from that seen in PD.
Dysarthria is often an early development in PSP and may be severe.
What are some other neurologic features of PSP?
Gait and balance disturbances are also early developments in persons with PSP and unexplained falling may even be the presenting feature of the disease. This is in marked contrast to PD.
Another prominent difference between the two disorders is that tremor is typically not present in PSP.
Behavioral dysfunction in the form of emotional lability and dementia are frequent in PSP and may develop early in the course of the disease process.
What is the defining clinical feature of PSP – the feature that most clearly separates it from PD and ultimately permits diagnosis?
The development of a characteristic eye movement abnormality, called a supranuclear gaze palsy.
The initial clinical manifestation of the supranucleur gaze palsy is what?
impairment of volitional downgaze (aka may present as messy eater, dirty tie sign, or difficulty descending stairs). This is diametrically different from PD, where difficulty with upgaze is often present.
With progression of the oculomotor dysfunction, upgaze is then affected and eventually horizontal gaze also becomes impaired.
What causes the impairment of eye movement in PSP?
Not due to paralysis of the extraocular muscles, but rather due to dysfunction at a level above the brainstem nuclei involved with eye movements, prompting the term “supranuclear” gaze palsy for the abnormality.
That the eyes are actually still capable of moving can be demonstrated by the oculocephalic maneuver, in which the patient is asked to fix his or her gaze on a point while the head is then passively rotated in a vertical or horizontal plane and full excursion of the eyes elicited. Individuals with PSP may also display difficulty with opening closed eyes when asked to do so, despite being able to do so spontaneously. This is termed apraxia of eyelid opening.
Other features of PSP?
Persons with PSP may also develop signs of pyramidal tract involvement, such as positive Babinski signs, and may also display a variety of sleep disturbances.
From a gross anatomic standpoint, PSP is characterized by what?
midbrain and cerebral cortical atrophy.
Microscopically, neuronal loss and gliosis are present in multiple areas, including the substantia nigra and other areas of the rostral midbrain, including the pedunculopontine nucleus. The globus pallidus is also prominently affected.
____________, composed of unpaired straight filaments that contain abnormally phosphorylated tau protein are a pathological hallmark of PSP. Thus PSP is called a tauopathy.
Neurofibrillary tangles
_______ is the most prominent neurochemical abnormality of PSP.
Nigrostriatal dopaminergic deficiency. However, other neurotransmitter systems are also affected, including cholinergic (ACh), GABAergic and noradrenergic (Nor).
What is MSA?
Multiple system atrophy (MSA) is another parkinsonism-plus syndrome, characterized by parkinsonian features plus additional distinctive clinical and pathological abnormalities.
The microscopic hallmark of MSA is the presence of:
glial cytoplasmic inclusion bodies that, like PD, stain for alpha synuclein.
Neuronal loss and gliosis, with consequent atrophy are characteristic of HD. This is especially evident in what areas?
the caudate and putamen.
What is Kayser-Fleisher ring?
The formation of brown pigment around the outer rim of the cornea. The brown discoloration is produced by copper deposition in Descemet’s membrane within the cornea.
They may be very difficult or even impossible to see on routine eye examination in individuals with brown eyes, requiring slit lamp examination by an experienced ophthalmologist or neuroophthalmologist. Kayser-Fleischer rings are virtually always present in individuals with WD who have developed neurological or psychiatric dysfunction, but may not be present in persons with only hepatic symptoms or in presymptomatic individuals.
What is this?
This slide demonstrates a sunflower cataract in WD. These typically can only be seen on slit-lamp exam and are due to copper deposition in the lens.
A microscopic hallmark of WD is what?
the Opalski cell, which is an altered glial cell that can be found in the basal ganglia of individuals with WD.
