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Parkinson's Disease - Neurology

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Nadia Shams
Nadia Shams

Parkinson's disease is a progressive neurological disorder caused by degeneration of dopamine-producing neurons in the brain. The document presents a case study of a 70-year old male farmer diagnosed with Parkinson's based on symptoms of mild tremors, rigidity, and bradykinesia. The patient was started on levodopa treatment to control his symptoms as there is no cure for Parkinson's, and treatment aims to prevent progression and delay motor complications.

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Parkinson’s Disease BY DR NADIA SHAMS ASSOCIATE PROFESSOR RIHS - ISLAMABAD DrNadiaShamsRIHSIslamabad
Content  Introduction  Cause and pathogenesis  Case Study: ➢ Symptoms ➢ Diagnosis ➢ Treatment ➢ Conclusion Dr Nadia Shams RIHS Islamabad
oIntroduction  It is a progressive neurological condition  Results from the degeneration of dopamine-producing neurons in the substantia nigra  Afflicted 25,000 people in Malaysia  Various types of Parkinson’s disease  Risk factors: ➢ Middle aged and increased risk with age ➢ Hereditary ➢ Men (1.5 times more) ➢ Environmental exposure to toxins Dr Nadia Shams RIHS Islamabad
Symptoms  4 major symptoms: ➢ Rigidity – muscles are tensed and contracted ➢ Resting tremor – trembling which is most obvious when the patient is at rest or when stressed ➢ Bradykinesia – slowness in initiating movement ➢ Loss of postural reflexes or instability – poor balance and coordination  Non-motor symptoms ➢ Anxiety disorders, depression, sleep disturbances, orthostatic hypotension, olfaction dysfunction, dysphagia, sialorrhoea, dementia, psychosis and visual hallucinations Dr Nadia Shams RIHS Islamabad
Diagnosis and Treatment  Diagnosis: ➢ Neurological examination ➢ Autopsy of brain to find lewy bodies (trademark characteristic) ➢ Judgement of physicians  Treatment: ➢ Medications ➢ Diet ➢ Exercise, physical and speech therapy ➢ Surgery ❖ Cryothalamotomy ❖ Pallidotomy ❖ Deep brain stimulation Dr Nadia Shams RIHS Islamabad
oCauses and Pathogenesis  Degradation of dopaminergic neuron.  Free radicals.  Neurotoxin - MPTP  Genetic factors. Dr Nadia Shams RIHS Islamabad
Degradation of Dopaminergic Neuron  Substantia nigra pars compacta.  Death of neuron.  Symptoms of PD don’t appear until 50-80% of the neurons in the pars compacta have died.  Cause of death of neuron is not known. Dr Nadia Shams RIHS Islamabad
Free Radicals  Unpaired electrons that can easily react with surrounding molecules and destroy them.  Metabolism of dopamine by MAO produce hydrogen peroxide.  Glutathione normally breaks down the hydrogen peroxide quickly.  Reduced glutathione = loss of protection against free radicals → cell damage Dr Nadia Shams RIHS Islamabad
Neurotoxin - MPTP  1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) – neurotoxin.  MPTP crosses the blood-brain barrier and oxidized to 1-methyl-4-phenylpyridinium (MPP+) by monoamine oxidase B (MAO)-B  MPP+ selectively enters dopamine neurons via the dopamine transporter.  MPP+ inhibiting Complex I → leads to cell death via energy deficit. Dr Nadia Shams RIHS Islamabad
Genetic Factors • Mutation of SNCA genes in chromosome 4. • 2 types of alterations: • Alanine is replaced with threonine. • Cause alpha-synuclein to misfold. • SNCA genes is inappropriately duplicated or triplicated. • Extra copies of the gene lead to an excess of alpha-synuclein. • Aggregate (Lewy bodies) and attract other protein. • Clog neuron and impair the function of neuron. Dr Nadia Shams RIHS Islamabad
oCase Study: • 70 YEAR-OLD MALE • FARMER • REFERRED TO A MOVEMENT DISORDERS OUTPATIENT CLINIC Dr Nadia Shams RIHS Islamabad
Symptoms 1. Nondisabling intermittent resting tremor of left hand  Result of pallidal dysfunction  Triggered by specific loss of dopa minergic projections from retrorubral area Dr Nadia Shams RIHS Islamabad
2. Present of myerson  Eyes blinking when tapped on glabella (glabellar reflex)  Involuntary reflex disorder Dr Nadia Shams RIHS Islamabad
3. Mild signs of asymmetrical cogwheel rigidity and bradykinesia (left > right)  Cause to muscular aches and sensation of fatigue  Face become masklike, opened mouth, drooling and reduced blinking  Underscaling of movement commands in internally generated movements  Reflect the role of the basal ganglia in selecting and reinforce appropriate patterns of cortical activity during movement preparation and performance Dr Nadia Shams RIHS Islamabad
4. Normal gait and balance and postural reflexes  Under activity in the left cerebellar hemisphere with contrast of over activity in vermis  Associated with loss of lateral gravity shift in parkinsonian gait  Loss of postural reflexes  No tendency of falling forward  No difficulty of walking, turning and stopping Dr Nadia Shams RIHS Islamabad
Diagnostic Test  No specific test.  Usually based on present of symptoms.  Referral time should not be more than 6 weeks and not exceed two weeks in severe case.  No specific lab test used for diagnosis.  Follow – up= every 6 to 12 months. Dr Nadia Shams RIHS Islamabad
 Suggested method include: ➢ Neurologic examination ➢ Oculomotor examination ➢ Electroencephalograms (EEG) ➢ Single photon emission computed tomography (SPECT) Dr Nadia Shams RIHS Islamabad
❑ Neurological examination ➢ Patient’s medical and family history ➢ Observe sign and symptoms present. ➢ Suggested symptoms include: ❖ Bradikinesia ❖ Tremor ❖ Hypokinesia ❖ Rigidity ➢ Patient had normal cognition and myerson sign is present. ➢ Intermittent mild tremor was observed as well as cogwheel rigidity and bradykinesia. Dr Nadia Shams RIHS Islamabad
❑ Oculomotor examination ➢ To check abnormalities of eye movement, generation, and control. ➢ Normal in patient. ❑ Single photon emission computed tomography (SPECT) ➢ Show dramatic (50%) loss of striatal uptake in patient compared to normal individual. ❑ Electroencephalograms ➢ Record patient’s brain electrical activity. Dr Nadia Shams RIHS Islamabad
Single photon emission computed tomography (SPECT) Dr Nadia Shams RIHS Islamabad
Treatment According to the case study the patient was on initiation of treatment:In early-stage disease, the pharmacological options for the treatment of PD are multiple.  Levodopa: ➢ is a medicine that the brain converts to dopamine. ➢ is a medicine used to control symptoms of Parkinson's disease and used at all stages of the disease. ➢ Levodopa does not slow the disease process, but it improves muscle movement and delays severe disability. ➢ long-term levodopa therapy within 5 to 10 years can cause complication to occur such as Dyskinesia. Dr Nadia Shams RIHS Islamabad
 Dopamine agonist: ➢ Example of drugs:pramipexole,ropinirole ➢ directly stimulate the receptors in nerves in the brain that normally would be stimulated by dopamine. ➢ used in the early stages of Parkinson’s disease to reduce symptoms. ➢ effective in people who have been newly diagnosed with the disease (especially those younger than 60). ➢ Not effective as levodopa in reducing symptom but can prevent long term effect caused by levodopa. Dr Nadia Shams RIHS Islamabad
 Monoamine oxidase type B inhibitor ➢ MAO-B is an enzyme in our brain that naturally breaks down several chemicals in our brain including dopamine. ➢ Prevent the breakdown dopamine. ➢ they prevent the removal of dopamine between nerve endings and enhance release of dopamine from nerve cells. ➢ Example of drug: Rasagiline and selegiline. ➢ used in the early stages, to treat very mild symptoms (such as resting tremor) and delay the need for levodopa. ➢ rasagiline or selegiline may be added to levodopa treatment to reduce motor fluctuations , increase the time of effect of the levodopa. Dr Nadia Shams RIHS Islamabad
 Amantadine ➢ treat people who are in the early stages of Parkinson's disease. ➢ It is best used in people who have mild to moderate symptoms. ➢ cause greater amounts of dopamine to be released in the brain. ➢ can be used with levodopa in the later stages of Parkinson's disease to reduce dyskinesias. Dr Nadia Shams RIHS Islamabad
 Anticholinergic ➢ Example of drugs: benztropine,biperiden ➢ Anticholinergic medicines decrease levels of acetylcholine to achieve a closer balance with dopamine levels. ➢ In order to reduce the symptom. Dr Nadia Shams RIHS Islamabad
Decision pathway for the initiation of medication Dr Nadia Shams RIHS Islamabad
 Levodopa ( L-Dopa) ➢ the most effective antiparkinsonian medication. ➢ “start low, go slow” approach, L-dopa can be started at a dose of 50 mg daily (e.g., ¼ tablet of Madopar® 200/50 mg) increasing every 3-7 days by 50 mg to an initial maintenance dose of 50-100 mg 3x daily.  Selegiline ( Jumex and Selegos) ➢ usual dose is 10 mg in the morning. ➢ has a mild antiparkinsonian effect.Dr Nadia Shams RIHS Islamabad
 Dopamine agonist ➢ Next most potent class of drug after L-dopa. Dopamine agonist Usual Starting Dose Maximum recommend ed Dose Piribedil (Trivastal Retard *) 25-50mg 300mg/d Ropinirole immidiate release ( Requip *) 0.25mg 24mg/d Ropinirole Prolong Release (Requip PD*) 2mg 24mg/d Dr Nadia Shams RIHS Islamabad
 Anticholinergic agents  These include trihexyphenidyl or benzhexol (Apo-Trihex® and Benzhexol®)(1 or 2 mg 2-3x daily) and orphenadrine (Norflex®) (50 mg 2-3x daily).  Non-Pharmocologic Management ➢ physiotherapy: stretching and strengthening exercises and balance training. ➢ occupational therapy: lifestyle adaptations and assessment of safety in the home environment. ➢ speech therapy: rehabilitation techniques to strengthen speech for improved communication. ➢ Dietitian: advice from them. Dr Nadia Shams RIHS Islamabad
Conclusion  Patient has idiopathic Parkinson’s disease  There is no cure but therapies are available  Treatments aims to: ➢ Prevent clinical progression ➢ Improvement of parkinsonism ➢ Delay of motor complications  Complications: choking, falls and side effects of drugs  Prognosis: normal life expectancy for treated patients Dr Nadia Shams RIHS Islamabad
Dr Nadia Shams RIHS Islamabad

More Related Content

Parkinson's Disease - Neurology

  • 1. Parkinson’s Disease BY DR NADIA SHAMS ASSOCIATE PROFESSOR RIHS - ISLAMABAD DrNadiaShamsRIHSIslamabad
  • 2. Content  Introduction  Cause and pathogenesis  Case Study: ➢ Symptoms ➢ Diagnosis ➢ Treatment ➢ Conclusion Dr Nadia Shams RIHS Islamabad
  • 3. oIntroduction  It is a progressive neurological condition  Results from the degeneration of dopamine-producing neurons in the substantia nigra  Afflicted 25,000 people in Malaysia  Various types of Parkinson’s disease  Risk factors: ➢ Middle aged and increased risk with age ➢ Hereditary ➢ Men (1.5 times more) ➢ Environmental exposure to toxins Dr Nadia Shams RIHS Islamabad
  • 4. Symptoms  4 major symptoms: ➢ Rigidity – muscles are tensed and contracted ➢ Resting tremor – trembling which is most obvious when the patient is at rest or when stressed ➢ Bradykinesia – slowness in initiating movement ➢ Loss of postural reflexes or instability – poor balance and coordination  Non-motor symptoms ➢ Anxiety disorders, depression, sleep disturbances, orthostatic hypotension, olfaction dysfunction, dysphagia, sialorrhoea, dementia, psychosis and visual hallucinations Dr Nadia Shams RIHS Islamabad
  • 5. Diagnosis and Treatment  Diagnosis: ➢ Neurological examination ➢ Autopsy of brain to find lewy bodies (trademark characteristic) ➢ Judgement of physicians  Treatment: ➢ Medications ➢ Diet ➢ Exercise, physical and speech therapy ➢ Surgery ❖ Cryothalamotomy ❖ Pallidotomy ❖ Deep brain stimulation Dr Nadia Shams RIHS Islamabad
  • 6. oCauses and Pathogenesis  Degradation of dopaminergic neuron.  Free radicals.  Neurotoxin - MPTP  Genetic factors. Dr Nadia Shams RIHS Islamabad
  • 7. Degradation of Dopaminergic Neuron  Substantia nigra pars compacta.  Death of neuron.  Symptoms of PD don’t appear until 50-80% of the neurons in the pars compacta have died.  Cause of death of neuron is not known. Dr Nadia Shams RIHS Islamabad
  • 8. Free Radicals  Unpaired electrons that can easily react with surrounding molecules and destroy them.  Metabolism of dopamine by MAO produce hydrogen peroxide.  Glutathione normally breaks down the hydrogen peroxide quickly.  Reduced glutathione = loss of protection against free radicals → cell damage Dr Nadia Shams RIHS Islamabad
  • 9. Neurotoxin - MPTP  1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) – neurotoxin.  MPTP crosses the blood-brain barrier and oxidized to 1-methyl-4-phenylpyridinium (MPP+) by monoamine oxidase B (MAO)-B  MPP+ selectively enters dopamine neurons via the dopamine transporter.  MPP+ inhibiting Complex I → leads to cell death via energy deficit. Dr Nadia Shams RIHS Islamabad
  • 10. Genetic Factors • Mutation of SNCA genes in chromosome 4. • 2 types of alterations: • Alanine is replaced with threonine. • Cause alpha-synuclein to misfold. • SNCA genes is inappropriately duplicated or triplicated. • Extra copies of the gene lead to an excess of alpha-synuclein. • Aggregate (Lewy bodies) and attract other protein. • Clog neuron and impair the function of neuron. Dr Nadia Shams RIHS Islamabad
  • 11. oCase Study: • 70 YEAR-OLD MALE • FARMER • REFERRED TO A MOVEMENT DISORDERS OUTPATIENT CLINIC Dr Nadia Shams RIHS Islamabad
  • 12. Symptoms 1. Nondisabling intermittent resting tremor of left hand  Result of pallidal dysfunction  Triggered by specific loss of dopa minergic projections from retrorubral area Dr Nadia Shams RIHS Islamabad
  • 13. 2. Present of myerson  Eyes blinking when tapped on glabella (glabellar reflex)  Involuntary reflex disorder Dr Nadia Shams RIHS Islamabad
  • 14. 3. Mild signs of asymmetrical cogwheel rigidity and bradykinesia (left > right)  Cause to muscular aches and sensation of fatigue  Face become masklike, opened mouth, drooling and reduced blinking  Underscaling of movement commands in internally generated movements  Reflect the role of the basal ganglia in selecting and reinforce appropriate patterns of cortical activity during movement preparation and performance Dr Nadia Shams RIHS Islamabad
  • 15. 4. Normal gait and balance and postural reflexes  Under activity in the left cerebellar hemisphere with contrast of over activity in vermis  Associated with loss of lateral gravity shift in parkinsonian gait  Loss of postural reflexes  No tendency of falling forward  No difficulty of walking, turning and stopping Dr Nadia Shams RIHS Islamabad
  • 16. Diagnostic Test  No specific test.  Usually based on present of symptoms.  Referral time should not be more than 6 weeks and not exceed two weeks in severe case.  No specific lab test used for diagnosis.  Follow – up= every 6 to 12 months. Dr Nadia Shams RIHS Islamabad
  • 17.  Suggested method include: ➢ Neurologic examination ➢ Oculomotor examination ➢ Electroencephalograms (EEG) ➢ Single photon emission computed tomography (SPECT) Dr Nadia Shams RIHS Islamabad
  • 18. ❑ Neurological examination ➢ Patient’s medical and family history ➢ Observe sign and symptoms present. ➢ Suggested symptoms include: ❖ Bradikinesia ❖ Tremor ❖ Hypokinesia ❖ Rigidity ➢ Patient had normal cognition and myerson sign is present. ➢ Intermittent mild tremor was observed as well as cogwheel rigidity and bradykinesia. Dr Nadia Shams RIHS Islamabad
  • 19. ❑ Oculomotor examination ➢ To check abnormalities of eye movement, generation, and control. ➢ Normal in patient. ❑ Single photon emission computed tomography (SPECT) ➢ Show dramatic (50%) loss of striatal uptake in patient compared to normal individual. ❑ Electroencephalograms ➢ Record patient’s brain electrical activity. Dr Nadia Shams RIHS Islamabad
  • 20. Single photon emission computed tomography (SPECT) Dr Nadia Shams RIHS Islamabad
  • 21. Treatment According to the case study the patient was on initiation of treatment:In early-stage disease, the pharmacological options for the treatment of PD are multiple.  Levodopa: ➢ is a medicine that the brain converts to dopamine. ➢ is a medicine used to control symptoms of Parkinson's disease and used at all stages of the disease. ➢ Levodopa does not slow the disease process, but it improves muscle movement and delays severe disability. ➢ long-term levodopa therapy within 5 to 10 years can cause complication to occur such as Dyskinesia. Dr Nadia Shams RIHS Islamabad
  • 22.  Dopamine agonist: ➢ Example of drugs:pramipexole,ropinirole ➢ directly stimulate the receptors in nerves in the brain that normally would be stimulated by dopamine. ➢ used in the early stages of Parkinson’s disease to reduce symptoms. ➢ effective in people who have been newly diagnosed with the disease (especially those younger than 60). ➢ Not effective as levodopa in reducing symptom but can prevent long term effect caused by levodopa. Dr Nadia Shams RIHS Islamabad
  • 23.  Monoamine oxidase type B inhibitor ➢ MAO-B is an enzyme in our brain that naturally breaks down several chemicals in our brain including dopamine. ➢ Prevent the breakdown dopamine. ➢ they prevent the removal of dopamine between nerve endings and enhance release of dopamine from nerve cells. ➢ Example of drug: Rasagiline and selegiline. ➢ used in the early stages, to treat very mild symptoms (such as resting tremor) and delay the need for levodopa. ➢ rasagiline or selegiline may be added to levodopa treatment to reduce motor fluctuations , increase the time of effect of the levodopa. Dr Nadia Shams RIHS Islamabad
  • 24.  Amantadine ➢ treat people who are in the early stages of Parkinson's disease. ➢ It is best used in people who have mild to moderate symptoms. ➢ cause greater amounts of dopamine to be released in the brain. ➢ can be used with levodopa in the later stages of Parkinson's disease to reduce dyskinesias. Dr Nadia Shams RIHS Islamabad
  • 25.  Anticholinergic ➢ Example of drugs: benztropine,biperiden ➢ Anticholinergic medicines decrease levels of acetylcholine to achieve a closer balance with dopamine levels. ➢ In order to reduce the symptom. Dr Nadia Shams RIHS Islamabad
  • 26. Decision pathway for the initiation of medication Dr Nadia Shams RIHS Islamabad
  • 27.  Levodopa ( L-Dopa) ➢ the most effective antiparkinsonian medication. ➢ “start low, go slow” approach, L-dopa can be started at a dose of 50 mg daily (e.g., ¼ tablet of Madopar® 200/50 mg) increasing every 3-7 days by 50 mg to an initial maintenance dose of 50-100 mg 3x daily.  Selegiline ( Jumex and Selegos) ➢ usual dose is 10 mg in the morning. ➢ has a mild antiparkinsonian effect.Dr Nadia Shams RIHS Islamabad
  • 28.  Dopamine agonist ➢ Next most potent class of drug after L-dopa. Dopamine agonist Usual Starting Dose Maximum recommend ed Dose Piribedil (Trivastal Retard *) 25-50mg 300mg/d Ropinirole immidiate release ( Requip *) 0.25mg 24mg/d Ropinirole Prolong Release (Requip PD*) 2mg 24mg/d Dr Nadia Shams RIHS Islamabad
  • 29.  Anticholinergic agents  These include trihexyphenidyl or benzhexol (Apo-Trihex® and Benzhexol®)(1 or 2 mg 2-3x daily) and orphenadrine (Norflex®) (50 mg 2-3x daily).  Non-Pharmocologic Management ➢ physiotherapy: stretching and strengthening exercises and balance training. ➢ occupational therapy: lifestyle adaptations and assessment of safety in the home environment. ➢ speech therapy: rehabilitation techniques to strengthen speech for improved communication. ➢ Dietitian: advice from them. Dr Nadia Shams RIHS Islamabad
  • 30. Conclusion  Patient has idiopathic Parkinson’s disease  There is no cure but therapies are available  Treatments aims to: ➢ Prevent clinical progression ➢ Improvement of parkinsonism ➢ Delay of motor complications  Complications: choking, falls and side effects of drugs  Prognosis: normal life expectancy for treated patients Dr Nadia Shams RIHS Islamabad
  • 31. Dr Nadia Shams RIHS Islamabad