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

2.1.1.1. Monogeneic causes

2.1.1.1.1. Recessive

2.1.1.1.2. Dominant

2.1.1.2. Genetic risk factors

2.1.1.2.1. GBA

2.1.1.2.2. MAPT

2.1.1.2.3. PLA2G6

2.1.1.2.4. X-linked

2.1.1.2.5. UCHL-1 (disputed!)

2.1.1.2.6. GIGYF2 (disputed!)

2.1.1.2.7. FBXO7

2.1.1.2.8. NURR1

2.1.1.2.9. HtrA2/Omi

2.1.1.2.10. BST1?

2.1.2. Incidence

2.1.2.1. 8-18/100.000 /year

2.1.3. Prevalence

2.1.3.1. 1% of people >60 years

2.1.3.2. Increases with age

2.1.3.3. 0,3% in entire population of industrialised countries

2.1.4. Non-genetic

2.1.4.1. Risk factors

2.1.4.1.1. Well Established

2.1.4.1.2. Controversial

2.1.4.2. Risk reducing factors

2.1.4.2.1. Not well established

2.1.4.2.2. Smoking

2.1.4.2.3. Caffeine

2.1.4.2.4. (sub)acute onset: within 0-6 months; 1 month - 60%, 3 months - most

2.1.4.2.5. Controversial

2.1.4.3. Others?

2.1.4.3.1. Head trauma

2.1.5. Drug Induced

2.1.5.1. antipsychotics

2.1.5.1.1. classic - D2 receptor block

2.1.5.1.2. extrapyr. effects w/ 80% block

2.1.5.1.3. risk 10-40%; main: dose and potency, age, Female, pre-existent P.

2.1.5.1.4. reversible; recovery - 6+ months

2.1.5.1.5. atypical: <40-70% D2 occ.

2.1.5.2. anti-emetics

2.1.5.2.1. metoclopramide

2.1.5.2.2. domperidone - not crossing BBB; DIP rare

2.1.5.3. Calcium channel blockers

2.1.5.3.1. Women > Men (2:1-3:1)

2.1.5.3.2. >60y

2.1.5.3.3. nigrostriatal mitochondrial resp.chain disf. (by inhibition of D storage in presyn vesicles or by D2 r. occup.)

2.1.5.3.4. within 9-12 months

2.1.5.4. cholinomimetics

2.1.5.4.1. anticholinergics - th PD (rigidity&tremor)

2.1.5.4.2. AchE inhibitors

2.1.5.5. Chemotherapeutics

2.1.5.6. Dopamine depletors

2.1.5.6.1. reserpine (antihipertensive), tetrabenazine

2.1.5.6.2. depletion of D from presyn vesicles

2.1.5.6.3. methyldopa (D2 block; falseNT)

2.1.5.7. Others

2.1.5.7.1. meperidine

2.1.5.8. DIP

2.1.5.8.1. most frequent causes = drugs which block D2 r. in the striatum

2.1.5.8.2. 4-37% treated patients

2.1.5.8.3. increasing w/ age

2.1.5.8.4. if persisting -> underlying idiopathic

2.1.5.8.5. sy

2.2. Disease mechanisms

2.2.1. Mitochondrial dysfunction

2.2.1.1. Calcium signalling

2.2.1.2. Fission and fusion

2.2.1.3. Mitophagy

2.2.2. Lysosomal dysfunction

2.2.2.1. ATP13A2 mutations

2.2.2.1.1. protein mistargeting

2.2.2.1.2. ER retention

2.2.2.1.3. lysosomal acidification

2.2.2.2. GBA mutations

2.2.2.2.1. glycolipid metabolism dysregulation

2.2.3. Misfolding of proteins

2.2.3.1. Prion mechanism?

2.2.3.2. aggregation

2.2.3.2.1. accumulation

2.2.3.3. taupoathies

2.2.3.4. synucleinopathies

2.2.3.5. Autocatalytic acticity

2.2.4. Trafficking and vesicle release

2.2.4.1. alpha synuclein

2.2.4.1.1. synaptic problems

2.2.4.1.2. reduction of vesicles

2.2.4.2. PINK1 mutations

2.2.4.2.1. modulate dopaminergic transmission

2.2.5. Link with cancer?

2.2.5.1. mTOR signalling in PD

2.2.5.2. PD genes dysregulated in cancer

2.2.5.3. Altered risk for come cancers in PD

2.2.6. Cell loss

2.2.6.1. Ventrolateral Snc cells

2.2.6.1.1. Dopamine toxicity?

2.2.6.1.2. Alpha synuclein aggregation?

2.2.6.1.3. Neuromelalin neurons more susceptible

2.2.6.1.4. Calcium signaling?

2.2.6.2. 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

2.3.5.1. Basal ganglia anatomy

2.3.5.1.1. Subthalamic Nucleus

2.3.5.1.2. Striatum

2.3.5.1.3. Globus Pallidus

2.3.5.1.4. Sn

2.3.5.2. Basal ganglia physiology

2.3.5.2.1. Direct pathway

2.3.5.2.2. Indirect pathway

2.3.5.3. Limbic system

2.3.6. Autonomic nervous system

2.3.6.1. Structure

2.3.6.1.1. Pre-ganglionic

2.3.6.1.2. Post-ganglionic

2.3.6.2. dysautonomia

2.3.6.2.1. gastrointeestnial

2.3.6.2.2. cardiovascular

2.3.6.2.3. urogenital

2.3.6.2.4. sudomotor

2.3.6.2.5. thermoregulatory

2.3.6.3. Regulation

2.3.6.3.1. Hypothalamus

2.3.6.3.2. 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

5.1.1.1. stereotactical

5.1.1.1.1. DBS

5.1.1.1.2. ablation

5.1.1.2. (fetal cells implantation)

5.1.2. Physical Therapy

5.1.2.1. Treadmill

5.1.2.2. Dual Task

5.1.2.3. Transfers

5.1.2.4. 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

5.2.1.1. Levodopa

5.2.1.2. Dopamine agonists

5.2.1.3. Anticholinergic

5.2.1.4. Amantadine

5.2.2. Neuroprotective drugs

5.2.2.1. New Evidence

5.2.2.1.1. Nicotine and Caffeine

5.2.2.1.2. Polyphenol (Green Tea)

5.2.2.1.3. Pramixezole

5.2.2.1.4. Co-enzyme Q10

5.2.2.1.5. Creatine

5.2.2.1.6. NSAIDs

5.2.2.1.7. Acupuncture

5.2.2.1.8. Vitamin E

5.2.2.2. Classic Treatment

5.2.2.2.1. MAO Inhibitors

5.2.2.2.2. NMDA blockers

5.2.2.2.3. GDNF proteins

6. Symptoms and Diagnosis

6.1. Differential Diagnosis

6.1.1. http://www.mdvu.org/library/disease/pd/par_dd.asp

6.1.2. http://bestpractice.bmj.com/best-practice/monograph/147/diagnosis/differential.html

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

6.2. http://cmk-proxy.mf.uni-lj.si:2054/full_record.do?product=WOS&search_mode=GeneralSearch&qid=3&SID=U1Jiip17DKpJkbpdjaD&page=1&doc=3

6.3. Radiological diagnostics

6.3.1. MRI

6.3.1.1. Diffusion MRI

6.3.1.2. a large number of sequences

6.3.1.2.1. T1W, TW2

6.3.1.2.2. PD

6.3.1.2.3. T2W gradient echo

6.3.1.2.4. Diffusion -weighted imaging

6.3.1.2.5. diffusion tensor imaging (DTI)

6.3.2. Transcranial sonography

6.3.3. CT

6.3.4. PET

6.3.4.1. the assessment of neurotransmitter systems (predominantly the pre- and postsynaptic dopaminergic functions, also serotonergic and cholinergic system

6.3.4.2. glucose metabolism in the various Parkinsonian syndromes

6.3.4.3. neuroinflammation, load of amyloid plaques, and cardiac sympathetic denervatio

6.3.5. SPECT

6.4. DIAGNOSTIC CRITERIA

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: http://archneur.ama-assn.org/cgi/content/full/56/1/33?ijkey=b9c0a672fa63aad85443a37e4f155c355377526c

6.4.4. http://jnnp.bmj.com/content/79/4/368.full

6.5. Symptoms

6.5.1. Primary motor symptoms

6.5.1.1. Resting tremor

6.5.1.2. Bradykinesia

6.5.1.3. Rigidity

6.5.1.4. Postural Instability (Impaired Balance and Coordination)

6.5.2. Secondary motor symptoms

6.5.2.1. Gait and posture symptoms

6.5.2.1.1. Stooped posture

6.5.2.1.2. Poverty of movement (decreased arm swing)

6.5.2.1.3. Dystonia

6.5.2.2. Other

6.5.2.2.1. Fatigue

6.5.2.2.2. Cramping

6.5.2.2.3. "Masking"

6.5.2.2.4. Impaired gross motor coordination

6.5.2.2.5. Impaired fine motor dexterity&motor coordination

6.5.2.2.6. Micrographia

6.5.2.2.7. Akathisia

6.5.2.3. Speech and swallowing disturbances

6.5.2.3.1. Slurred speech

6.5.2.3.2. Softness of voice

6.5.2.3.3. Difficulty swallowing

6.5.2.3.4. Drooling

6.5.3. Non-motor symptoms

6.5.3.1. Sleep disorders

6.5.3.2. Cognitive/neurobehavioural abnormalities

6.5.3.2.1. Dementia/confusion

6.5.3.2.2. Compulsive behaviour

6.5.3.2.3. Bradyfrenia

6.5.3.2.4. Memory difficulties

6.5.3.2.5. Fear or anxiety

6.5.3.2.6. Depression

6.5.3.3. Autonomic dysfunction

6.5.3.3.1. gastrointeestnial

6.5.3.3.2. cardiovascular

6.5.3.3.3. urogenital

6.5.3.3.4. sudomotor

6.5.3.3.5. thermoregulatory

6.5.3.4. Sensory abnormalities

6.5.3.4.1. Pain

6.5.4. http://jnnp.bmj.com/content/79/4/368.full

6.6. Diagnosis

6.6.1. medical history & neurological exam - Esra

6.6.1.1. medical history

6.6.1.1.1. risk factors

6.6.1.1.2. symptoms

6.6.1.2. neurological examination

6.6.1.2.1. Washing hands, introducing yourself, and asking permission (consent) to examine:)

6.6.1.2.2. Gait and Stance

6.6.1.2.3. Face

6.6.1.2.4. Inspection

6.6.1.2.5. Trunk

6.6.1.2.6. Arms

6.6.1.2.7. Extra

6.6.2. Radiology EEG - Mojica

6.6.2.1. Radiological diagnostics

6.6.2.1.1. MRI

6.6.2.1.2. Transcranial sonography

6.6.2.1.3. CT

6.6.2.1.4. PET

6.6.2.1.5. SPECT

6.6.2.2. Neurophysiological diagnostics

6.6.2.2.1. EEG

6.6.2.2.2. MEG (Magnetoencephalography

6.6.2.2.3. Evoked potentials

6.6.2.2.4. ERD (Event related Desynchronisation) combines the elements of EEG with the MRCP

6.6.2.3. node

6.6.3. biochem & genetics - Vlada

6.6.3.1. Biochem

6.6.3.1.1. Vit D

6.6.3.1.2. Biomarker in blood after Mn exposure - parkin 2

6.6.3.1.3. alpha synulein nitration in mononuclear cells as a biomarker (+autophagy)

6.6.3.1.4. mRNA ???

6.6.3.2. Genetics

6.6.3.2.1. parkin gene mutations (more often in patients with an early onset of PD, Hispanic ethnicity patients and family history of PD)

6.6.3.2.2. PLA2G6 mutations

6.6.3.2.3. 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

6.8.1. http://www.patientslikeme.com/parkinsons/community

6.8.2. http://www.pdf.org/en/symptoms