PARKINSONS DISEASE

Dr Rocksy Fransisca VS, SpS Click to edit Master subtitle style Faculty of Medicine UPH Siloam Hospitals Lippo Village

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Objective
Student should be able to: Understand the patophysiology of Parkinson Disease Differentiated Parkinson Disease and Parkinsonism Describe the clinical symptoms of Parkinson Disease

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Definition of PD

Parkinson disease is a progressive neurologic disorders caused by degeneration of dopamine neurons Parkinson disease is second most common degenerative disorders of the aging brain after Alzheimer Disease

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History

JAMES PARKINSON described in his classical monograph an Essay on The Shaking Palsy (1817)
involuntary tremolous motion, with lessened muscular power, in parts not in action and even when supported: with the prospensity to bend the trunk forward and to pass from a walking to a running pace; the 4/18/12 sense and intellect being

History
In later nineteenth century, JEANMARTIN CHARCHOT described a pill rolling tremor and masked face as particular features of PD. He commented on the absence of weakness and the occationals impairment of intellect In 1917 LEWY first described the characteristic eosinophilic intracytoplasmic inclusion bodies in 4/18/12 various regions of the brainstem. But

Epidemiology

PD makes up approximately 80% of cases of parkinsonism PD begins between the age of 40 and 70; the mean age of onset of PD occurring in sixth decades 5-10% of PD patients experience onset of symptom before age 40;

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Develop under age 21 : juvenile PD Develop from age 21 40 : young onset PD

Epidemiology
Incidence : 5-24/100.000 (worldwide) 20.5/100.000 (USA) Prevalence: 57-317/100.000 worldwide 300/100.000 USA/ Canada (Strickland & Bertoni, 2004) Prevalence of PD rising slowly with aging population 4/18/12

Etiology
No definite single etiology is confirmed for primary PD PD may result from a complex interaction between environmental toxic factors, genetic susceptibility traits and aging In more than 90% of cases, PD arise as sporadic condition Pathology is characterized by 4/18/12 dopaminergic neuronal

Etiology

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Etiology

(continue)

Many cellular mechanism have been proposed, including oxidative stress, premature apoptosis, loss of neurotrophic factors, glutamate toxicity, inflammatory processes, mitochondrial dysfunction, neuromelanin degeneration and so on On familial forms of PD, found several gene abnormalities in the 4/18/12 ubiquitin-proteosomal system and

PD Pathogenesis

Common intersecting pathways underlying PD pathogenesis. Both environmental factors and mutations in familial PD-linked genes encoding -synuclein, parkin, DJ-1, PINK1 and LRRK2 are associated with PD pathogenesis. These pathogenic mutations and environmental factors are known to cause disease due to mitochondrial dysfunction, oxidative damage, abnormal protein aggregation and protein phosphorylation compromising key roles of dopaminergic neuronal 4/18/12 function and survival. Environmental factors similar to pesticides and

Parkinsonian Syndromes

Primary parkinsonism Parkinson disease

Parkinson-plus syndrome

Secondary parkinsonism Drug induced: dopamine antagonist and depletors Hemiatrophy-parkinsonism Hydrocephalus: normal pressure hydrocephalus Hypoxia Infectious: postencephalitic Metabolic: parathyroid dysfunction Toxin: Manganese, CO, MPTP, cyanide, carbon disulfide Trauma 4/18/12

Cortical-basal ganglionicdegeneration Dementia syndrome: Alzheimer disease, diffuse lewy-body disease, frontotemporal dementia Lytico-bodig (Guamanian parkinsonnism dementia ALS) Multiple system atrophy syndrome: striatal degeneration, shy-drager syndrome, sporadic OPCA, motor neuron disease-parkinsonism Progressive Palidal atrophy Progresive supranuclear palsy

Familial neurodegenerative disease

Huntingtons disease Hallervorden-spatz disease Lubag (X-linked dystoniaparkinsonism)

Pathologic stage of PD
(proposed by Braak et al)

Stage 1

Medulla oblongata and olfactory bulb lesion in dorsal nucleus of cranial nerve IX and X, intermediate reticular formation, olfactory bulb, and anterior olfactory muscle Pontine tegmentum pathology of stage 1 plus lesion in caudal raphe nuclei, giganto cellular reticular nucleus and sub ceruleus complex Midbrain pathology of stage 2 plus lesion in pars compacta of substansia nigra Basal pros encephalon and meso cortex pathology of stage 3 plus pros encephalic lesion, antero medial temporal meso cortex and allocortex (CA-2 plexus) Neocortical pathology of stage 4 plus lesion in prefrontal cortex and sensory association neocortical area

Stage 2

Stage 3

Stage 4

Stage 5

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Stage 6

Clinical features

The four cardinal sign of PD are :

Tremor Rigidity Bardykinesia Postural instability

Onset is insidious and difficult to ascertain precisely Tremor is oscillation of body part Rigidity refers to increased resistance (stiffness) when the joint is passively 4/18/12 flexed and extended

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Clinical features

The best clinical predictors of a pathology diagnosis of PD are:

Asymmetric of onset Presence of resting tremor Good response to dopamine medication therapy

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The clinical diagnosis of

Biological markers
Over at least 2 decades, functional neuroimaging of nigrostriatal dopaminergic pathway with PET and SPET has been refined as a tool in quantifying functional dopaminergic terminal in striatum Studies using PET have found an increase in glucose metabolism as well as a reduction of flourodopa 4/18/12 uptake and retention in basal ganglia

Clinical diagnosis (Hughes)

It is POSSIBLE if one of the following is present : tremor (either resting or postural), rigidity, or bradykinesia It is PROBABLE if two of the major features (TRAP) are present; or if resting tremor, rigidity or bradykinesia are asymmetric It is DEFINITE if three of the major

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UK Parkinsons Disease society Brain Bank

Step 1 3 Bradykinesia at least three of the following symptom At least one the following criteria: (prospective) criteria:

Criteria diagnosis of

J Neurol Neurosurg Psychiatry, April 2008; 79:368-376

Rigidity Unilateral onset 4 6 Hz rest tremor Rest tremor Postural instability not caused by primary Progressive disorder visual, vestibular, cerebellar or proprioseptive dysfunction Persistent asymmetric primarily affecting side of onset Excellent response (70% 100%) to Step 2 levodopa Exclude other cause of Parkinsonism 4/18/12 Severe levodopa induced chorea

NINDS Diagnosis Criteria for Parkinson Disease

Group A features (characteristic of PD)

(National Institute of Neurological Disorders and Stroke)

J Neurol Neurosurg Psychiatry, April 2008; 79:368-376

Resting tremor Bradykinesia Rigidity Asymmetric onset

Group B features (suggestive or alternative diagnosis)

Features usual early in clinical course Prominent postural instability in first 3 4/18/12 years after symptom onset

NINDS Diagnosis Criteria for Parkinson Disease

(continue)

J Neurol Neurosurg Psychiatry, April 2008; 79:368-376

Criteria for definite PD

All criteria for probable PD are met; and Histopathological confirmation of diagnosis is obtained at autopsy

Criteria for probable PD

At least three of the four features in group A are present; and None of the features in group B is present (note: symptom duration 3 years is necessary to meet this requirement); and 4/18/12

Clinical criteria for the diagnosis or exclusion of Parkinson Disease

Samii A, Parkinsons Disease, Lancet 2004;363:1783-1793

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Exposure Exclusion Clinically criteria Diagnosis to drug that can possible cause criteria PD parkinsonism, One of the following: such as asymmetric neuroleptics, resting tremor, some emetics asymmetric medication, rigidity or tetrabenazine, asymmetric reserpin, bradykinesia flunarizine and Clinically cinnarizine probable PD

The early symptom of PD

may be non specific and difficult to ascertain precisely

Fatique Reduced energy Joint stiffness (especially of the

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Tremor
Resting tremor is the most common presenting feature of PD Approximately 70% noticed tremor as the first symptom It may be present in one or more limb, usually asymmetric Tremor is typically present when the limb is at rest, limb in the position of postural maintenance Diminish with voluntary activity but 4/18/12

Tremor (continue)

The jaw, tongue, head and trunk are rarely affected; although in a severe as to transmitted to the trunk and head Tremor limited to head / neck likely sign of essential tremor PD tremor is generally less likely to be exacerbate with coffein or improved with alcohol Parkinson related postural tremor (re-emergent tremor) Appearance of tremor is often delayed after the patient assumes an outstretched horizontal position

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Tremor in PD vs Essential Tremor

FEATURE
Age of onset Family history Frequency Tremor characteristic Influence factor Rest Action Mental concentration Writing Walking Alcohol Postural tremor Distribution other than limb Neuroimaging dopaminergic system Mid brain sonography Neuropathology Tratment

PARKINSON DISEASE
55-75 +/4 6 Hz Supinasi - pronasi Increase Decrease Decrease Decrease (micrographia) Increase Re-emergent Face, jaw, hips, chin

ESSENTIAL TREMOR
10 - 80 ++ 5 - 10 Flexion - extention Decrease Increase Increase Increase (tremulous) Decrease Decrease Without latency Head, voice

Marked dopaminergic deficits Mild Marked hyper-echogenicity Nigrostriatal degeneration, lewy bodies Mild Mild cerebellar degeneration

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Anticholinergic, dopaminergic Alcohol, beta blockers, drugs, DBS primidone, topiramat,

Bradykinesia

One of the most disabling manifestation of PD 80% to 90% of patients Slowness of voluntary movement and poverty of normal asscociated movement Akinesia : impliying nearly absent voluntary movement
The movement is too small to be seen The time to generate movement to 4/18/12 extremely long

Bradykinesia (continue)
Eye presents with saccadic hypometria Face with reduced frequency of blinking and diminished facial animation. Facial expression is reduced (hypomimia or masked facies) Hypophonia: bradykinesia of respiratory and the vocal cord muscle New onset of stuttering or re4/18/12 emergence of childhood stuttering

Rigidity
Parkinson himself did not speak of rigidity in his description. Charchot identified this important sign and differentiated it from spasticity Is continuous and uniform increase in muscle tone, felt as smooth resistance throughout the range of passive movements > 90% of patients 4/18/12

Rigidity

(continue)

May be associated with pain, and painfull shoulders is one of the most frequent initial manifestation of PD. Commonly misdiagnosed as arthritis, bursitis or rotator cuff injury Rigidity causes stooped posture and forward shift of center of gravity (propulsion), flexed limb and decrease arm swing when walking In addition, patients may suffer 4/18/12 dystonia especially in their feet, such

Rigidity vs spasticity

Rigidity in PD

Implies pathology of the extrapyramidal system Absence of pyramidal weakness Decrease strenght; movement is slow and seemingly weak but not really weakness

Spasticity: is of spinal origin.

Spasticity is velocity dependent (clasp knife) and association with upper motor neuron sign, eq hyper reflexia, babinsky 4/18/12

Postural Instability

Usually last symptom to occur Indicative of progression to advance stage of disease Postural instability is likely to be the combined effect of rigidity and bradykinesia It is mainly due to the loss of postural reflexes, which causes difficulties in positional adjustments
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Postural Instability
These symptom are unfortunately relatively resistant to pharmacological treatment. Patients may require physical therapy or rely on walking aids The most common cause of falls and contributes significantly to the risk of hips fractures The long latency of the onset of falls differentiated PD from other neurodegenerative disorders (such as PSP, MSA)

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Parkinsonian Gait
Gait is defined as a complex motor and mental skill that, when properly executed, requires the integration of mechanism of locomotion with those of balance, motor control, cognition and musculoscelethal function Gait is the most essential motor tasks require for independence and ambulation PD is the second most common 4/18/12

Parkinsonian Gait

(continue)

Stooped Posture: PD patient stand in general flexion (trunk is flexed forward) Stand immobile and rigid with paucity of automatic movement of limbs and a mask-like, fixed facial expression with infrequent blinking A rest tremor often involved the finger and wrist at 4-5 cycles per second
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Parkinsonian Gait
Gait should be assessed in every PD patient as part of basic evaluation

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Time walk test The patient 10 m UP and GO asked to perform stand up and line straightwalk forward walking for 3 meters, turn of Measurement around and step gait speed, return back step length, and to his / her chair frequency Evaluate: Self-initiated gait turning, gait can improved initiation and

Festinating gait
Typical disturbance of locomotion in PD; rarely in symptomatic parkinsonism It consist of rapid small steps taken in an attempt to keep the center of gravity above the feet while the trunks leans forward involuntarily and shift COG forward To compensate and prevent falling: people with PD increase steeping 4/18/12

Freezing
Motor block; is a form of akinesia (loss of movement) and is one of the most disabling symptom of PD Is characteristic features of PD, and common cause of falls Less frequently in patients whose main symptom is tremor Most common affect the leg during walking (but arms and eyelid can also be involved) Typically manifest as a sudden and 4/18/12

Natural progression
The progression of PD is varies among patients; but may be related to different subtypes It affect the upper and or lower limb asymmetrically, and eventually, most patient will be affected on both side When PD begins in elderly patient, decline is more rapid than in middle age onset patients; and bradykinesia, rigidity and balance problems 4/18/12 predominate over tremor

Nonmotor feature of PD
Neuropsychiatric dysfunction Mood disorders Apathy and an-hedonia Frontal executive dysfunction Dementia and psychosis Sleep fragmentation and insomnia REM sleep behavior disorders (RBD) Periodic limb movements in sleep (PLMS) / Restless legs syndrome (RLS) Excessive daytime somnolence Orthostatic hypotension Urogenital dysfunction constipasion Olfactory dysfunction Abnormal sensations pain

Sleep disorders

Autonomic dysfunction

Sensory symptom and pain 4/18/12

Parkinson Disease vs Parkinsonism

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Management

Parkinson disease (PD) is a chronic disorder that requires broad-based management including patient and family education, support group services, general wellness maintenance, exercise, and nutrition. Treatment of PD can be divided into :
1. 2. 3.

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Pharmacologic Non-pharmacologic Surgical therapy.

Non-Pharmacologic treatment of Parkinson disease

EXERCISE AND PHYSICAL THERAPY : Exercise will not

slow the progression of akinesia, rigidity, or gait disturbance, but it can prevent some secondary orthopedic effects of rigidity and flexed posture such as shoulder, hip, and back pain, and it may also improve function in some motor tasks. Brisk walks, swimming, and water aerobic exercises are particularly useful. Referral to a physical therapist or exercise group may be a good way to get patients started in such activities.

Speech therapy : Dysarthria and hypophonia are common

manifestations of Parkinson disease (PD).

Nutrition : Elderly patients with chronic illness are at risk for

poor nutrition and weight loss. No specific diet influences the course of Parkinson disease (PD), A high fiber diet and adequate hydration help manage the constipation of PD. Large, high-fat meals that slow gastric emptying and interfere with medication absorption should be avoided. Dietary protein restriction is not necessary except in some patients with 4/18/12

Pharmacologic treatment of Parkinson disease

The major drugs available for symptomatic therapy include: 1. Levodopa 2. MAO B inhibitors 3. Dopamine agonists 4. COMT inhibitors 5. Anticholinergic agents 6. Amantadine

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Management of comorbid problems associated with PD

Patients with PD may experience problems related to the disease itself or to the medications used to treat it. These comorbid problems include psychosis, hallucinations, daytime sleepiness, depression, fatigue and dementia. PSYCHOSIS AND HALLUCINATIONS : visual hallucinations, delusions, and paranoia. Antiparkinsonian drugs can be reduced or stopped in reverse order of their potency and effectiveness if hallucinations are causing disability The atypical neuroleptics clozapine and quetiapine may be helpful in low doses. DEMENTIA : DAYTIME SLEEPINESS : involves efforts to improve 4/18/12 nocturnal sleep hygiene and to treat causes of poor

Surgical Therapy

Deep Brain Stimulation

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Thank you
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