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Parkinson's Disease by Mind Map: Parkinson
3.5 stars - 2 reviews range from 0 to 5

Parkinson's Disease

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

Pathogenesis

Epidemiology

Genetic, Monogeneic causes, Recessive, Parkin, Protein: E3 ubiquitin ligase, Autophagy, Proteasomal protein degredation, Parkinson:, early onset, most common recessive form, devoid of LB?, PINK1, Protein: Mitochondrial kinase, Ca2+ signalling, Respiratory chain (complex I+IV), Parkinson's:, 2nd most common recessive form, DJ-1, Protein: Mitochondrial homeostasis, Very rare, ATP13A2, Protein: lysosomal P-type ATPase, Lysosomal dysfunction, Dominant, SNCA, Protein: alpha-synuclein, Main component of Lewy bodies, alpha-synuclein deposition, Parkinson's:, mutation, duplications and triplications of the gene cause PD, LRRK2, Protein: kinase, regulation of vesicle dynamics at the presynaptic membrane, Parkinson's, mutations are most common cause of PD, Genetic risk factors, GBA, Involved in Gaucher's disease, most common genetic risk factor for PD, MAPT, autosomal dominant FTLD with Parkinsonism, PLA2G6, Phospholipase A2, X-linked, Unknown gene at locus Xq21-25, UCHL-1 (disputed!), GIGYF2 (disputed!), FBXO7, E3 ubiquitin ligase, NURR1, HtrA2/Omi, Function: mitochondrial protease, disputed! but only mouse model with phenotype, BST1?, identified in one GWAS but not others, involved in calcium mobilization

Incidence, 8-18/100.000 /year

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

Non-genetic, Risk factors, Well Established, Age, Age related changes in cellular function, Controversial, Gender, 3:2 Male-female ratio, Ethnicity, Caucasian > African or Asian, Diatary Iron, Risk reducing factors, Not well established, Oestrogens, Dietary intake, Antioxidants, Vitamin E, Fat & fatty acids, Dietary vitamin B6 in absence of B12 and folate, Low cholesterol / cholesterol lowering drugs, Smoking, Caffeine, inhibitor of the adenosine A2 receptor, improves motor deficits in a mouse model of PD.42, (sub)acute onset: within 0-6 months; 1 month - 60%, 3 months - most, Controversial, Alcohol, Others?, Head trauma

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, potentiating cholinergic transmission, th of Alzheimer's, physostigmine in the past; DIP, esp tremor, 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, D2 block - similar to PD, other drugs & toxins, non-parkinsonian motor and cognitive sy, most do not benefit from Ldopa th, postsyn D2 blockade or postsyn lesions in striatal cells, atypical syndrome + absence of Ldopa effect, other causes, parkinson-plus syndromes, vascular parkinsonism, age, progression, typical sy

Disease mechanisms

Is parkinson's Disease not just accelerated aging?   Look at all levels of brain function

Mitochondrial dysfunction, Calcium signalling, Fission and fusion, Mitophagy

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

Misfolding of proteins, Prion mechanism?, aggregation, accumulation, Lewy bodies, taupoathies, synucleinopathies, Autocatalytic acticity

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

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

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

Anatomy & Pathology

Noradrenaline

Acetylcholine

Olfactory system

Associative circuit

Nigrostriatal Part of the brain, Basal ganglia anatomy, Subthalamic Nucleus, Striatum, Globus Pallidus, Sn, Compact part, Ventrolateral cells, Reticulated part, Basal ganglia physiology, Direct pathway, Indirect pathway, Limbic system

Autonomic nervous system, Structure, Pre-ganglionic, Choinergic, Nicotinic, myelinated fibers, sympathic/parasympathic, Post-ganglionic, Sympathic, Noradrenergic, most axons, Nicotinic, only: Adrenal gland and Sweat gland, Parasympathic, Cholinergic, muscarinic, Anatomy, Enteric, Plexus of Auerbach, Plexus of Meissner, Cholinergic and opioidergic cells, dysautonomia, gastrointeestnial, Dysphagio, Dorsal Motor Nucleus of Vagus Nerve, cardiovascular, orthostatic hypotension, urogenital, urinary, sexual, sudomotor, thermoregulatory, Regulation, Hypothalamus, Projections, reticular formation, hippocampus, cerebral cortex, basal ganglia, entorrhinal cortex, thalamus, Signalling, endocrine system, Brainstem: solitary tract nucleus, spinal cord nuclei, preganglionic autonomic neurons, Pathology, Alfasynucleinopathy, Lewybody, Locations, peripheral autonomic nerve system, Are the depositions a sign of cell death?, Are these depositions undermining function of the cell?, Are all peripheral nerve cells involved or only a specific subset, What's the cause of the autonomic denervation?, Some non-motor symptoms are responsive to dopamine treatment, does dopamine slow down neurodegeneration?, Brainstem

Social & economical burden

Progressive

Home monitoring

Carers

Costs

Michael J Fox

Untreatable

Threpetlika

Research Methods

Quantification

Pd scales

Braak

No good animal model

Dopamine receptor imaging

Ablation

Therapy

Non-pharmacological

Surgery, stereotactical, DBS, ablation, (fetal cells implantation)

Physical Therapy, Treadmill, Dual Task, Transfers, Balance

Psychological Therapy

Speech and Language Therapy

Occupational Therapy

Pharmacological

Symptomatic treatment, Levodopa, Dopamine agonists, Anticholinergic, Amantadine

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

Symptoms and Diagnosis

Differential Diagnosis

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

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

Essential tremor

Progressive supranuclear palsy

Multiple system atrophy

Corticobasal degeneration

Diffuse Lewy body dementia

AD

Drug-induced parkinsonism

Vascular parkinsonism

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

Radiological diagnostics

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

Transcranial sonography

CT

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

SPECT

DIAGNOSTIC CRITERIA

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

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

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

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

Symptoms

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

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

Non-motor symptoms, Sleep disorders, Cognitive/neurobehavioural abnormalities, Dementia/confusion, Compulsive behaviour, Bradyfrenia, Memory difficulties, Fear or anxiety, Depression, Autonomic dysfunction, gastrointeestnial, Dysphagio, Dorsal Motor Nucleus of Vagus Nerve, cardiovascular, orthostatic hypotension, urogenital, urinary, sexual, sudomotor, thermoregulatory, Sensory abnormalities, Pain

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

Diagnosis

medical history & neurological exam - Esra, medical history, risk factors, family history of neurologic disease, sex, advancing age, agricultural work, declining oestrogen levels, rural living, genetic factors, low levels of B vitamin folate, head trauma, any drugs?, symptoms, Rigidity - an increased tone or stiffness in the muscles, increasing during movement and may be painful, Tremor - potentially worse on one side of the body and may involve the arms, legs, head, neck, face, and jaw, Slowness in beginning to move, Poor balance with sudden movement or changes in body position, Difficulty in walking, including a decreased arm swing, Shuffling steps, Difficulty in making turns, The inability to take the next step, neurological examination, Washing hands, introducing yourself, and asking permission (consent) to examine:), Gait and Stance, Festinating gait, Decreased arm swing, Difficulty turning and initiating movements, Postural instability, Face, glabellar tap (keep blinking - normally adjust), normal eye movements but abnormal vertical gaze, Inspection, Hypomimia(decreased facial expression), Blepharoclonus (fine eyelid tremor), resting (tremorbrought out by distraction - such as conversation), tardive dyskinesia(chewing movements of the mouth - drug treatment side effect), Trunk, Axial rigidity (found in the 'supranuclear palsy' form of Parkinson's disease), Arms, - Normal muscle bulk / reflexes / power, Tremor ('pill rolling', more pronounced at rest - as opposed to cerebellar tremors that are more pronounced upon initiation of movement), Increased tone - leadpipe rigidity (move whole arm around elbow joint) & cog-wheel rigidity (support forearm and flex/extend the flat palm at the wrist - cogwheeling is the jerky 'stepwise' movement that is felt due to tremor superimposed upon rigidity) ? features enhanced when asking the patient to move the other arm up and down - 'distractor', Bradykinesia (slowness of movement - observed when patient is asked to flap arms up and down), Finger-nose pointing (tremor decreases), Extra, Micrographia (small writing), - Examine the observations chart for a postural BP drop (in the 'multisystem atrophy' form of Parkinson's), Examine the drug chart (is this perhaps a drug-induced 'Parkinsonism' - caused by anti-dopaminergic drugs such as metoclopromide), Examine the cerebellar system's function (also affected in 'multisystem atrophy')

Radiology EEG - Mojica, Radiological diagnostics, MRI, Diffusion MRI, a large number of sequences, T1W, TW2, PD, T2W gradient echo, Diffusion -weighted imaging, diffusion tensor imaging (DTI), Transcranial sonography, loss of neuromelanin and increase of iron (hyperechogenity) in the SN, CT, 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, SPECT, 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, Neurophysiological diagnostics, EEG, Minor slowing of the EEG (also in non demented patients), MEG (Magnetoencephalography, widespread slowing of resting state brain activity at non-demented PDpatients, evident in early stage, Evoked potentials, VEP (visual evoked potential),, ERG (electroretinogram), blockade of dopaminergic cells in the retina my dopamin antagonists results in an abnormal PERG in healthy subjectsm. in PD-decrease of the PERG for median frequencies and increased contrast treshold, Slowing of the VEP mor outspoken in demented, OEP (olfactory), early diagnostics?, abnormal desynchronization of of the in untreated PD,, BAEP (bulbus olfactorius), normal,, SEP (somato sensory sistem activation), N30, ERP (electroretinogram),, MEP (magnetic), ERD (Event related Desynchronisation) combines the elements of EEG with the MRCP, node

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

Time plan

11:15 - Planning the strategy for research

12:00 - Lunch

13:30 - Research

15:15 - Working on the presentation

16:30 - Presentation Skills training (altogether)

17:30 - final review of your presentation

18:00 - Presentation to Professors

LINKS

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

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