Movement Disorders 1 Flashcards
Main categories of hyperkinetic movement disorders
1) Dystonia
2) Chorea
3) Tremor
4) Myoclonus
5) Tic
Parkinsonism: Description
Akinesia/bradykinesia
Rigidity
Tremor at rest
Postural instability
Gait freezing
Flexion posture
Dystonia: Description
Παρατεταμένες ή διαλείπουσες μυικές συσπάσεις, οι οποίες προκαλούν ανώμαλες, συχνά επαναλαμβανόμενες κινήσεις, θέσεις ή και τα δύο.
Τα φαινομενολογικά χαρακτηριστικά των δυστονικών κινήσεων είναι:
* η σχετικά μεγάλη διάρκεια (σε σύγκριση με τον μυόκλονο και τη χορεία)
* η ταυτόχρονη σύσπαση αγωνιστών και ανταγωνιστών μυών
* η στροφική κίνηση του προσβεβλημένου μέρους του σώματος
* η συνεχής σύσπαση της ίδιας ομάδας μυών
* η εμφάνιση ή επιδείνωση των δυστονικών κινήσεων με την εκούσια κίνηση
Chorea: Description and Differential diagnosis
Ακούσιες, ακανόνιστες, μη ρυθμικές, απότομες, ταχείες, μη σταθερές κινήσεις οι οποίες μεταφέρονται από ένα μέρος του σώματος σε άλλο.
Το χαρακτηριστικό της χορείας είναι ότι οι χοριακές κινήσεις είναι απρόβλεπτες και τυχαίες όσον αφορά τη χωρική και χρονική κατανομή τους.
Differential diagnosis:
Huntington disease
Neuroacanthocytosis
Post-infectious chorea
Drug-induced chorea (e.g. levodopa, typical neuroleptics)
Vascular chorea
Autoimmune chorea (e.g. lupus)
Chorea gravidarum (a complication of pregnancy which can be associated with eclampsia and its effects upon the basal ganglia)
Hyperthyrodism
Nonketotic diabetes mellitus
Tic: Description and Differential diagnosis
Stereotyped, automatic, purposeless movements and vocalizations
Differential diagnosis:
Tourette syndrome
Cerebral palsy/developmental delay syndromes
Autism
Huntington disease
Myoclonus: Description and Differential diagnosis
Sudden, shock-like movements
Differential diagnosis:
Physiologic myoclonus
Essential myoclonus
Metabolic encephalopathy
Postanoxic myoclonus
Progressive myoclonic epilepsy
Tremor: Description
Repetitive oscillation of a body part
Describe:
1) Athetosis
2) Ballism
3) Akathisia
1) συνεχείς, βραδείες, άρρυθμες, σχετικά μακράς διάρκειας ερπυστικές κινήσεις που συνδυάζουν κάμψη, έκταση, απαγωγή και προσαγωγή.
Προσβάλλουν περισσότερο τα άκρα (κυρίως τα περιφερικά τμήματα), αλλά και το πρόσωπο, την κεφαλή και τον κορμό.
2) Κινήσεις πολύ μεγάλου εύρους με βίαιες εκτιναξεις των προσβεβλημένων άκρων από τα κεντρικά τους τμήματα.
Unilateral ballism is termed hemiballism and is most often caused by an infarct of the contralateral subthalamic nucleus (Luys).
3) Κινήσεις ανήσυχες (συνεχές περπάτημα, σταύρωμα/ ξεσταύρωμα των ποδιών κ.α.) που συνοδεύονται συνήθως από ένα αίσθημα αδημονίας με ακατάσχετη τάση για κίνηση.
Bradykinesia, rigidity and rest tremor definition
Bradykinesia is defined as slowness of movement plus a decrement in amplitude/speed or progressive hesitations/halts as movements are continued
Rigidity is a velocity-independent resistance (sometimes referred to as “lead-pipe resistance”) to passive movement of the major joints while the patient is in a relaxed position
Rest tremor is a 4 to 6 Hz tremor that is observed in a fully resting limb and is suppressed when initiating movement
Parkinson disease
1) mean age of onset
2) men to women ratio
1) 56 years in both sexes
2) nearly 2:1
Parkinson disease risk factors
●Age (the most important risk factor for PD)
●Sex – Males have a higher risk of PD than females
Factors associated with lower lifetime estrogen exposure (eg, early menopause, higher parity) have been associated with increased PD risk in females
●Genetics – A family history of PD in a first-degree relative is associated with a two- to threefold increase in the risk of PD.
Monogenic forms of PD account for less than 10 percent of PD cases and span autosomal dominant, autosomal recessive, and X-linked inheritance patterns. Most have a younger age of onset compared with sporadic PD
Aside from monogenic forms of PD, heterozygous pathogenic variants in the glucocerebrosidase 1 (GBA1) gene are another important genetic risk factor for PD. Other lysosomal enzyme-encoding genes have also been found to alter risk
●Environmental exposures
*Exposure to pesticides
*Exposure to nitrogen dioxide in air pollution
*High consumption of dairy products
*Living in urban or industrial areas with high release of copper, manganese, or lead
*Exposure to hydrocarbon solvents, particularly trichloroethylene
*Living in rural areas
*Farming or agriculture work
*The use of well water
*High dietary intake of iron, especially in combination with high manganese intake
*Reduced levels of dietary and sunlight-derived vitamin D
●Comorbidities
*Excess body weight and metabolic syndrome
*Type 2 diabetes mellitus
*History of traumatic brain injury
*History of melanoma or prostate cancer
Parkinson disease protective factors
The most consistently identified negative associations, or protective factors, for PD are cigarette smoking, caffeine consumption, and physical exercise.
Basal ganglia:
Direct pathway
Aμεσο μονοπάτι: η πληροφορία μεταφέρεται από τον φλοιό στο ραβδωτό σώμα καταλήγοντας στο έσω τμήμα της ωχράς σφαίρας και τη δικτυωτή μοίρα της μέλαινας ουσίας και θεωρείται ότι έχει διεγερτικό ρόλο
The direct pathway starts with cells in the striatum that make inhibitory connections with cells in the GPint.
The GPint cells in turn make inhibitory connections on cells in the thalamus.
Thus, the firing of GPint neurons inhibits the thalamus, making the thalamus less likely to excite the neocortex.
When the direct pathway striatal neurons fire, however, they inhibit the activity of the GPint neurons.
This inhibition releases the thalamic neurons from inhibition (i.e., it disinhibits the thalamic neurons), allowing them to fire to excite the cortex.
Thus, because of the “double negative” in the pathway between the striatum and GPint and the GPint and thalamus, the net result of exciting the direct pathway striatal neurons is to excite motor cortex.
Basal ganglia indirect pathway
Έμμεσο μονοπάτι: η πληροφορία μεταφέρεται από τον φλοιό στο ραβδωτό σώμα και αφού περάσει από το έξω τμήμα της ωχράς σφαίρας και τον υποθαλαμικό πυρήνα καταλήγει στο έσω τμήμα της ωχράς σφαίρας και τη δικτυωτή μοίρα της μέλαινας ουσίας ενώ ο ρόλος του πιστεύεται ότι είναι ανασταλτικός.
The indirect pathway starts with a different set of cells in the striatum.
These neurons make inhibitory connections to the external segment of the globus pallidus (GPext).
The GPext neurons make inhibitory connections to cells in the subthalamic nucleus, which in turn make excitatory connections to cells in the GPint. (Remember that the subthalamic-GPint pathway is the only purely excitatory pathway within the intrinsic basal ganglia circuitry.)
The GPint neurons make inhibitory connections on the thalamic neurons.
When the GPint cells are active, they inhibit thalamic neurons, thus making cortex less active.
When the subthalamic neurons are firing, they increase the firing rate of GPint neurons, thus increasing the net inhibition on cortex.
Firing of the GPext neurons inhibits the subthalamic neurons, thus making the GPint neurons less active and disinhibiting the thalamus.
However, when the indirect pathway striatal neurons are active, they inhibit the GPext neurons, thus disinhibiting the subthalamic neurons.
With the subthalamic neurons free to fire, the GPint neurons inhibit the thalamus, thereby producing a net inhibition on the motor cortex.
Basal ganglia pathways: what changes in PD
In PD, a reduction of dopamine-producing neurons leads to dopamine depletion in the substantia nigra and in the nigrostriatal pathway to the caudate and putamen.
This, in turn, results in relative overactivity of the indirect pathway, functionally disinhibiting the STN.
Decreased inhibition of the direct pathway causes additional disinhibition of the output nuclei (GPi and SNr).
Increased output from GPi causes increased inhibition of the thalamus and reduced excitatory input to the motor cortex, which is ultimately expressed as bradykinesia and other parkinsonian signs.
Parkinson disease pathologic hallmarks
The brains of patients with PD show depigmentation (αποχρωματισμός) (from loss of neuromelanin), neuronal loss, and gliosis, particularly in the substantia nigra pars compacta (SNc) and in the pontine locus ceruleus (υπομέλας τόπος).
These same areas are populated by Lewy bodies, which are round, eosinophilic, intracytoplasmic inclusions that stain positive for alpha-synuclein protein.
Lewy bodies are also found in the basal nucleus of Meynert, the cerebral cortex, the sympathetic ganglia, the dorsal vagal nucleus, the myenteric plexus of the intestines, and in the cardiac sympathetic plexus.
Parkinson disease genes
Which is the most prevalent monogenic cause of PD?
Mutation in LRRK2
Lewy body composition
Lewy bodies are made up mainly of alpha-synuclein and ubiquitin and also contain calbindin, synphilin-1, complement proteins, microfilament subunits, tubulin, microtubule-associated protein 1 and 2, and a parkin substrate protein called Pael-R
Parkinson disease diagnostic criteria
Parkinson disease absolute exclusion criteria
Parkinson disease red flags
Parkinson disease prodromal symptoms
Are they specific for PD?
●Rapid eye movement (REM) sleep behavior disorder (RBD)
●Constipation
●Hyposmia/olfactory dysfunction
They are not specific to PD and can also be seen with other synucleinopathies, such as DLB and MSA
Craniofacial manifestations of PD
Hypomimia (masked facial expression)
Decreased eye blinking
Speech disturbances (hypokinetic dysarthria, hypophonia)
Dysphagia (due to bradykinesia of the pharyngeal musculature)
Sialorrhea
Visual manifestations of PD
Blurred vision
Impaired contrast sensitivity
Hypometric saccades
Impaired vestibuloocular reflex
Impaired upward gaze and convergence
Lid apraxia
Musculosceletal manifestations of PD
Micrographia
Dystonia
Myoclonus
Camptocormia (severe anterior flexion of the thoracolumbar spine)
Pisa syndrome (subacute axial dystonia with lateral flexion of the trunk, head, and neck)
Kyphosis
Scoliosis
Difficulty turning in bed
Gait manifestations of PD
Shuffling, short-stepped gait
Freezing
Festination (επιτάχυνση βάδισης με μικρά βήματα)
Tremor in PD
1) Percentage
2) Location
3) Exacerbating factors
1) Tremor is the presenting symptom in approximately 70 to 80 percent of patients with PD and affects 80 to 100 percent of patients at some point in the course of the disease
2) Tremor usually starts unilaterally in the hand and then spreads contralaterally several years after the onset of symptoms. The side that is initially affected tends to be the more affected side throughout the course of the disease. The tremor can also involve the legs, lips, jaw, and tongue but rarely involves the head.
3) Anxiety, emotional excitement, or stressful situations can exacerbate the tremor.
How does bradykinesia affect PD patients
In the arms, bradykinesia typically starts distally with decreased manual dexterity of the fingers.
Patients often complain of difficulty performing simple tasks, such as buttoning clothes, tying shoelaces, double clicking a computer mouse, typing, or lifting coins from a pocket or purse.
In the legs, common complaints related to bradykinesia when walking include dragging the legs, shorter (shuffling) steps, or a feeling of unsteadiness. Patients may also have difficulty standing up from a chair or getting out of a car.
Also reduced arm swing, hypomimia, hypophonia, sialorrhea, micrographia
Clinical examination in PD
MDS-UPDRS scale
Rigidity in PD: Location
Rigidity, like tremor and bradykinesia, often begins unilaterally and typically on the same side as the tremor if one is present.
Rigidity eventually progresses to the contralateral side and remains asymmetric throughout the disease
Which symptom in PD is the least responsive in dopaminergic therapy?
postural instability
Major clinical subtypes of PD
●Tremor-dominant
●Akinetic-rigid
●Postural instability and gait difficulty
Parkinson disease non motor symptoms
●Cognitive dysfunction and dementia
●Psychotic symptoms (hallucinations and delusions)
●Mood disorders including depression, anxiety, and apathy/abulia
●Sleep disturbances
●Fatigue
●Autonomic dysfunction
●Olfactory dysfunction
●Gastrointestinal dysfunction
●Pain and sensory disturbances
●Dermatologic findings
Clinical features of PD dementia
A) Cognitive features
- Impaired attention
- Executive dysfunction
- Visuospatial dysfunction
- Impaired verbal memory
B) Behavioral features
- Apathy
- Changes in mood, including depression or anxiety
- Visual hallucinations
- Paranoid delusions
- Excessive daytime sleepiness
- Sleep disturbances, including fragmentation, nightmares, and REM sleep behavior disorder
A) percentage of psychotic symptoms in PD
B) Most common psychotic symptom in PD
A) 20 to 40 percent of drug-treated patients with PD
B) visual hallucinations
Greatest risk factor for nursing home placement in patients with PD
psychosis
Most common psychiatric disturbance in PD
Depression
PD treatment that may increase suicide rates
suicide rates may be increased after subthalamic nucleus deep brain stimulation
Discriminating characteristic between apathy and depression
mood, which is neutral in apathy and negative in depression
Sleep disorders in PD
1) Insomnia
2) Restless leg syndrome
3) REM sleep behavior disorder
Percentage of REM sleep disorder in PD
affects at least 50 percent of patients with clinically established PD
Autonomic problems in PD
orthostasis
constipation
dysphagia
diaphoresis
urinary difficulties
sexual dysfunction
Secondary parkinsonism causes
- Drug-induced (dopamine antagonists and depletors- Antipsychotic agents, metoclopramide, prochlorperazine, tetrabenazine, valproic acid)
- Hydrocephalus (normal-pressure hydrocephalus)
- Trauma
- Tumor
- Vascular (multi-infarct state)
- Metabolic (hypoparathyroidism, pseudohypoparathyroidism, chronic liver failure, extrapontine myelinolysis, end-stage kidney disease with diabetes, type 2 diabetes)
- Toxin (mercury, manganese, carbon monoxide, cyanide, MPTP)
- Infectious (Encephalitis lethargica, HIV/AIDS, neurosyphilis, prion disease, progressive multifocal leukoencephalopathy, toxoplasmosis)
- Hypoxia
- Genetic (Wilson disease, neurodegeneration with brain iron accumulation, neuroacanthocytosis)
Is postural instability an early sign of PD?
It does not appear until later in the course of the disease.
Thus, patients with parkinsonian signs who exhibit postural instability early in the course of the illness most likely have another form of parkinsonism.
Levodopa trial for PD
The majority of patients with idiopathic PD will enjoy a significant therapeutic response to an adequate long-term trial of moderate doses of levodopa (eg, 400 to 600 mg daily).
Complete absence of response to a dose of 1000 to 1500 mg/day for at least two months strongly suggests that the original diagnosis of PD was incorrect and that the diagnosis should be revised to one of the other parkinsonian syndromes
Role of conventional MRI in PD diagnosis
Brain MRI is not necessary in a patient with a classic presentation of PD, no other neurologic signs, and a good response to levodopa therapy
May be performed to exclude specific structural abnormalities (eg, hydrocephalus, tumor, or lacunar infarcts).
Brain MRI may also be helpful in patients with clinical findings that suggest atypical parkinsonism.
Role of DaTscan in PD diagnosis
Indications
It can reliably distinguish patients with PD and other parkinsonian syndromes associated with nigrostriatal degeneration (ie, MSA, PSP, and corticobasal degeneration) from controls or patients with essential tremor, but it cannot differentiate PD and the other parkinsonian syndromes from one another
It is suggested for the following scenarios:
●Patients for whom the diagnosis is unclear after serial clinical evaluations, such as those with long-standing ET whose tremor evolves to have characteristics of PD but fails to respond unequivocally to levodopa
●Patients suspected of having drug-induced parkinsonism (striatal uptake of the isotope should be normal in this setting)
●Patients who are possible candidates for deep brain stimulation but for whom the diagnosis of ET versus PD versus some other cause (eg, dystonia) is unclear and where an accurate diagnosis determines the target of deep brain stimulation (eg, thalamic ventral intermediate nucleus versus subthalamic nucleus/globus pallidus interna)
●To firmly establish the presence of nigrostriatal dopamine deficiency when recruiting for a clinical trial, particularly if the focus is neuroprotection
In which cases with parkinsonism is olfactory system affected?
Olfactory dysfunction is common in PD but is not associated with CBD, PSP, or vascular parkinsonism and is mild or nonexistent in MSA (exclusionary feature!).
Is autonomic testing useful in PD diagnosis?
Cardiac sympathetic denervation, as documented on MIBG myocardial scintigraphy, is relatively sensitive and specific for distinguishing PD from other neurodegenerative causes of parkinsonism
In which cases is genetic test useful in PD?
In the following patients with PD:
1) those with early-onset PD (younger than 40 years of age)
2) those who have a first-degree relative with PD and
3) those from a population with a higher prevalence of a monogenic form of PD, such as Ashkenazi Jewish or North African Berber
Parkinson disease differential diagnosis
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