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
