Parkinson's Disease

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Parkinson's Disease by Mind Map: Parkinson's Disease

1. Functional imaging with tracers targeting specifically the dopamine system and regional brain function may show discrete abnormalities helping the clinician shorten considerably the diagnostic process

2. Pathogenesis

2.1. Epidemiology

2.1.1. Genetic Monogeneic causes Recessive Dominant Genetic risk factors GBA MAPT PLA2G6 X-linked UCHL-1 (disputed!) GIGYF2 (disputed!) FBXO7 NURR1 HtrA2/Omi BST1?

2.1.2. Incidence 8-18/100.000 /year

2.1.3. Prevalence 1% of people >60 years Increases with age 0,3% in entire population of industrialised countries

2.1.4. Non-genetic Risk factors Well Established Controversial Risk reducing factors Not well established Smoking Caffeine (sub)acute onset: within 0-6 months; 1 month - 60%, 3 months - most Controversial Others? Head trauma

2.1.5. Drug Induced antipsychotics classic - D2 receptor block extrapyr. effects w/ 80% block risk 10-40%; main: dose and potency, age, Female, pre-existent P. reversible; recovery - 6+ months atypical: <40-70% D2 occ. anti-emetics metoclopramide domperidone - not crossing BBB; DIP rare Calcium channel blockers Women > Men (2:1-3:1) >60y nigrostriatal mitochondrial resp.chain disf. (by inhibition of D storage in presyn vesicles or by D2 r. occup.) within 9-12 months cholinomimetics anticholinergics - th PD (rigidity&tremor) AchE inhibitors Chemotherapeutics Dopamine depletors reserpine (antihipertensive), tetrabenazine depletion of D from presyn vesicles methyldopa (D2 block; falseNT) Others meperidine DIP most frequent causes = drugs which block D2 r. in the striatum 4-37% treated patients increasing w/ age if persisting -> underlying idiopathic sy

2.2. Disease mechanisms

2.2.1. Mitochondrial dysfunction Calcium signalling Fission and fusion Mitophagy

2.2.2. Lysosomal dysfunction ATP13A2 mutations protein mistargeting ER retention lysosomal acidification GBA mutations glycolipid metabolism dysregulation

2.2.3. Misfolding of proteins Prion mechanism? aggregation accumulation taupoathies synucleinopathies Autocatalytic acticity

2.2.4. Trafficking and vesicle release alpha synuclein synaptic problems reduction of vesicles PINK1 mutations modulate dopaminergic transmission

2.2.5. Link with cancer? mTOR signalling in PD PD genes dysregulated in cancer Altered risk for come cancers in PD

2.2.6. Cell loss Ventrolateral Snc cells Dopamine toxicity? Alpha synuclein aggregation? Neuromelalin neurons more susceptible Calcium signaling? Cells in Locus Coeruleus

2.3. Anatomy & Pathology

2.3.1. Noradrenaline

2.3.2. Acetylcholine

2.3.3. Olfactory system

2.3.4. Associative circuit

2.3.5. Nigrostriatal Part of the brain Basal ganglia anatomy Subthalamic Nucleus Striatum Globus Pallidus Sn Basal ganglia physiology Direct pathway Indirect pathway Limbic system

2.3.6. Autonomic nervous system Structure Pre-ganglionic Post-ganglionic dysautonomia gastrointeestnial cardiovascular urogenital sudomotor thermoregulatory Regulation Hypothalamus Pathology

3. Social & economical burden

3.1. Progressive

3.2. Home monitoring

3.3. Carers

3.4. Costs

3.5. Michael J Fox

3.6. Untreatable

3.7. Threpetlika

4. Research Methods

4.1. Quantification

4.2. Pd scales

4.3. Braak

4.4. No good animal model

4.5. Dopamine receptor imaging

4.6. Ablation

5. Therapy

5.1. Non-pharmacological

5.1.1. Surgery stereotactical DBS ablation (fetal cells implantation)

5.1.2. Physical Therapy Treadmill Dual Task Transfers Balance

5.1.3. Psychological Therapy

5.1.4. Speech and Language Therapy

5.1.5. Occupational Therapy

5.2. Pharmacological

5.2.1. Symptomatic treatment Levodopa Dopamine agonists Anticholinergic Amantadine

5.2.2. Neuroprotective drugs New Evidence Nicotine and Caffeine Polyphenol (Green Tea) Pramixezole Co-enzyme Q10 Creatine NSAIDs Acupuncture Vitamin E Classic Treatment MAO Inhibitors NMDA blockers GDNF proteins

6. Symptoms and Diagnosis

6.1. Differential Diagnosis



6.1.3. Essential tremor

6.1.4. Progressive supranuclear palsy

6.1.5. Multiple system atrophy

6.1.6. Corticobasal degeneration

6.1.7. Diffuse Lewy body dementia

6.1.8. AD

6.1.9. Drug-induced parkinsonism

6.1.10. Vascular parkinsonism


6.3. Radiological diagnostics

6.3.1. MRI Diffusion MRI a large number of sequences T1W, TW2 PD T2W gradient echo Diffusion -weighted imaging diffusion tensor imaging (DTI)

6.3.2. Transcranial sonography

6.3.3. CT

6.3.4. PET the assessment of neurotransmitter systems (predominantly the pre- and postsynaptic dopaminergic functions, also serotonergic and cholinergic system glucose metabolism in the various Parkinsonian syndromes neuroinflammation, load of amyloid plaques, and cardiac sympathetic denervatio

6.3.5. SPECT


6.4.1. National Institute of Neurological Disorders and Stroke (NINDS) diagnostic criteria for Parkinson’s disease (PD)

6.4.2. UK Parkinson’s Disease Society Brain Bank’s clinical criteria for the diagnosis of probable Parkinson’s disease

6.4.3. CRITERIA:


6.5. Symptoms

6.5.1. Primary motor symptoms Resting tremor Bradykinesia Rigidity Postural Instability (Impaired Balance and Coordination)

6.5.2. Secondary motor symptoms Gait and posture symptoms Stooped posture Poverty of movement (decreased arm swing) Dystonia Other Fatigue Cramping "Masking" Impaired gross motor coordination Impaired fine motor dexterity&motor coordination Micrographia Akathisia Speech and swallowing disturbances Slurred speech Softness of voice Difficulty swallowing Drooling

6.5.3. Non-motor symptoms Sleep disorders Cognitive/neurobehavioural abnormalities Dementia/confusion Compulsive behaviour Bradyfrenia Memory difficulties Fear or anxiety Depression Autonomic dysfunction gastrointeestnial cardiovascular urogenital sudomotor thermoregulatory Sensory abnormalities Pain


6.6. Diagnosis

6.6.1. medical history & neurological exam - Esra medical history risk factors symptoms neurological examination Washing hands, introducing yourself, and asking permission (consent) to examine:) Gait and Stance Face Inspection Trunk Arms Extra

6.6.2. Radiology EEG - Mojica Radiological diagnostics MRI Transcranial sonography CT PET SPECT Neurophysiological diagnostics EEG MEG (Magnetoencephalography Evoked potentials ERD (Event related Desynchronisation) combines the elements of EEG with the MRCP node

6.6.3. biochem & genetics - Vlada Biochem Vit D Biomarker in blood after Mn exposure - parkin 2 alpha synulein nitration in mononuclear cells as a biomarker (+autophagy) mRNA ??? Genetics parkin gene mutations (more often in patients with an early onset of PD, Hispanic ethnicity patients and family history of PD) PLA2G6 mutations LRRK2 3 -6% of PD familial cases and 2% of PD sporadic cases

6.7. Time plan

6.7.1. 11:15 - Planning the strategy for research

6.7.2. 12:00 - Lunch

6.7.3. 13:30 - Research

6.7.4. 15:15 - Working on the presentation

6.7.5. 16:30 - Presentation Skills training (altogether)

6.7.6. 17:30 - final review of your presentation

6.7.7. 18:00 - Presentation to Professors

6.8. LINKS