Parkinsonism What makes it different?

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Parkinsonism

What makes it different?

Praween Lolekha, MD. MSc. Neurology division, Department of Internal Medicine Thammasat University

What is Parkinsonism ?

•A motor syndrome with the following cardinal features: •Definite 2/6 •Probable 1/6 •Possible 2/6 Bradykinesia Rest tremor Rigidity Postural instability Flexed posture

Freezing or motor blocks

Differential diagnosis of

Parkinsonism

Parkinsonism Idiopathic Parkinson’s Disease (PD) Secondary

parkinsonism Parkinson-plus syndrome Heredodegenerative parkinsonism

- Drug-induced - Vascular parkinsonism - Normal pressure hydrocephalus (NPH) - CNS infection - Metabolic-toxic encephalopathy - Structural lesions - Head trauma - Progressive supranuclear palsy (PSP) - Corticobasal dengeneration (CBD) - Multiple system atrophy (MSA) - Diffuse Lewy body disease (DLB)

- Huntington’s disease - Wilson’s disease (WD) - Neuroacanthocytosis - Neurodegeneration with brain iron accumulation (NBIA) - Spinocerebellar ataxias (2,3,17) - Others

Red flags for Parkinsonism

•Young-onset : Juvenile (genetic) PD Wilson’s disease (WD), NBIA •Symmetric onset: MSA, PSP, VaP, NPH •Absent tremor : MSA, PSP, CBD, VaP, NPH •Ataxia : MSA, SCA

•Pyramidal signs : MSA, PSP, CBD, VaP, NPH •Neuropathy : MSA

•Early postural instability: PSP, MSA, VaP, NPH

Red flags for Parkinsonism

•Myoclonus : CBD, CJD

•Dementia : DLB, AD, CJD, PSP, VaD •Psychotic symptoms: DLB, AD •Focal cortical signs : CBD •Alien limb sign: CBD •Oculomotor deficits : PSP •Dysautonomia : MSA

•Non-response to levodopa: MSA, CBD, PSP, VaD, etc.

Secondary Parkinsonism

•Drug-induced parkinsoism

•Normal pressure hydrocephalus (NPH) •Cerebrovascular disease

•Toxins •Trauma

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Drug-induced parkinsonism

•Most common cause of 2nd parkinsonism •Dopamine blocking agents

•Signs & Symptoms

•Symmetrical onset

•Action and postural tremor: upper limbs, oral •Gradual and progressive (1-3 months) •Improve after discontinue drugs (may take as

long as 18 months)

Drug-induced parkinsonism

Cerebrovascular parkinsonism

•3-12% of parkinsonism •Arteriosclerosis risk factors •Multi-infarct parkinsonism •Lower body parkinsonism •No definite diagnosis criteria

•Parkinsonism with evidence of cerebrovascular disease

•Acute (1 month), progressive (1 year) onset with lesions at basal ganglia, thalamus, substantia nigra after a stroke

•Extensive subcortical white-matter lesions

Lower body parkinsonism

•Most common type of vascular parkinsonism •Gait freezing, start hesitation

•Wide-base shuffling gait •Normal upper extremities •No tremor

•Not response to levodopa treatment •Dementia, pseudobulbar palsy

Normal Pressure Hydrocephalus

•Gait apraxia •Subcortical dementia •Urinary incontinence

•Fisher’s test: removing 30-50cc of CSF and observing for improvement in symptoms over the next 24 hours (100% specificity, 30% sensitivity) •Predict response to ventriculoperitoneal shunt

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Infectious and parkinsonism

Encephalitis lethargica

• Von-Economo’s disease, 1917-1927 • No recurrence of the epidemic has since

been reported

• Fever, sore throat, headache, myalgia • Somnolent opthalmoplegia, sleepy sickness • Parkinsonism, catatonia, akinetic mutism • 40% mortality, 60% morbidity

• Unknown cause: post viral infection, Influenza? • Autoimmune: steptococcus gr. A infection?

Parkinson-plus syndrome

Multiple System Atrophy (MSA)

•

Striatonigral degeneration : MSA-P

•

Shy-Drager syndrome : MSA-A

•

Olivopontocerebellar atrophy: MSA-C

Pathology:

Glia cytoplasmic inclusion (GCIs)

GCIs + gliosis • Basal ganglia • Cerebellum • Pons • Inferior olivary nuclei • Spinal cord

•

Prevalence 1-5/100,000

•

Age onset 40-60 years old

•

Prognosis ~10 years

•

MSA-P: common in western

•

MSA-C: common in Asia

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•

Autonomic (at least 1 symptom)

•Orthostatic hypotension

•30mmHg systolic, 15mmHg diastolic

•3 minutes

•Syncope, light-headedness, dizziness •Erectile dysfunction

•Urinary incontinence •Constipation •“Cold-hand sign”

Multiple System Atrophy (MSA)

•

Parkinsonism

•Akinetic rigidity

•Postural tremor, myoclonus •May be asymmetrical involvement •Orofacial dystonia

•Anterocollis •Laryngeal dystonia

(inspiratory stridor)

•

Cerebellar symptoms

•Gait ataxia --> limb ataxia (late) •Scanning + spastic dysarthria •Dysmetric saccade

•Gaze-evoked nystagmus •Disequilibrium

•Early gait disorder, wide-based gait

Multiple System Atrophy (MSA)

•Pyramidal symptoms

•Hyperreflexia •Spastic dystonia •Extensor plantar response •Pseudobulbar palsy •REM sleep behavior disorder •Obstructive Sleep Apnea (OSA) •Pisa syndrome

Transverse pontine fibers degeneration

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Treatment

•Early response to levodopa 40%, < 2 years •Prevent complication

•Laryngeal dystonia •Orthostatic hypotension

•Fluid intake, high salt diet

•Elastic body garments

•Head-up at night

•Fludrocortisone (0.1-0.3mg/day)

•Dystonia- Botulinum toxin injection

Progressive Supranuclear Palsy (PSP)

•Steele-Richardson-Olszewski syndrome •Most common parkinson-plus syndrome •Prevalence 6-6.4/100,000

•Onset 60-70 years old •Prognosis ~10 years

Progressive Supranuclear Palsy (PSP)

Tau +ve Neurofibrillary tangle Tufted astrocyte Subthalamic nucleus Red nucleus Substantia nigra Pontine tegmentum Striatum Oculomotor nucleus Medulla Dentate nucleus

Macroscopic pathology

• Atrophy of midbrain tectum, tecmentum

• Atrophy of superior colliculi • Dilate third ventricle • Hypersignal periaqueductal

gray, red nucleus, midbrain

•Richardson’s syndrome (Classic PSP) •PSP-parkinsonism (PSP-P) (30%)

•PSP-pure akinesia with gait freezing (PSP-PAGF) •PSP-corticobasal syndrome (PSP-CBS)

•PSP-progressive non-fluent aphasia (PSP-PNFA)

Progressive Supranuclear Palsy (PSP)

•Parkinsonism: symmetrical

•Early postural instability: backward falls •Axial>limb rigidity

•Cervical dystonia: retrocollis •Facial dystonia: procerus sign •Mild postural, action tremor

•Frontal lobe dysfunction: apathy, disinhibition (applause sign)

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•

Extraocular movement

•Slow vertical saccades: first eye sign •Vertical gaze palsy : down-> up->

horizontal which corrected by VOR •Decreased nystagmus in optokinetic testing •Decrease eye blink

•Eyelid opening apraxia

PSP-Imaging study

Penguin sign

Morning glory sign

Treatment

• Levodopa response ~10-30% in the first 2 years

• Gait training

• Prevent falls

• Botulinum toxin injection

• +/- Anticholinergic

• - Dopamine agonists

• Co enzyme Q10

Corticobasal Syndrome (CBS) and

Corticobasal Degeneration (CBD)

• Cortex + Basal ganglia pathology

• Corticobasal syndrome (CBS: clinical phenotype) • CBD, AD, Pick’s disease, PSP, FTD, CJD, PML • Corticobasal degeneration (CBD: pathology)

• Age onset: 60-70 years old

• Hyperphosphorylated tau

• The least common parkinson-plus

Corticobasal Syndrome (CBS)

• Parkinsonism • Levodopa-resistant parkinsonism • Asymmetric akinetic rigid syndrome • Limb clumsiness • Limb dystonia

• Action tremor, myoclonus • Postural instability and falls

Fisted hand sign

Corticobasal Syndrome (CBS)

• Cortical lobe signs

• Apraxia : limb apraxia, ideomotor apraxia, limb-kinetic apraxia, orobuccal apraxia, apraxial of eyelid opening

• Aphasia, mutism • Alien limb (50%)

• Cortical sensory loss, visual neglect • Dementia

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Corticobasal degeneration (CBD)

Tau-positive ballooned neuron

Astrocytic plagues Tau accumulation in • Cortex • Basal ganglia • Thalamus • Brainstem

Asymmetry cortical atrophy

Treatment

•

Levodopa response 20%

•

-Dopamine agonists

•

+Benzodiazepine

•

+Botulinum toxin injection

•

Rx dementia, depression

Dementia with Lewy Bodies (DLB)

•2nd most common of dementia (15-30%) •Mean age 75 years old

•Dementia: 1 year rule of PDD

•Fluctuating, visuospatial, attention

•Parkinsonism: symmetrical onset, no tremor •Recurrent visual hallucination: vivid, complex •Extreme sensitivity to neuroleptics

Treatment

•

Cholinesterase inhibitors

•Rivastigmine

•

Memantine (NMDA receptor antagonist)

•

Atypical antipsychotic drugs

•Clonzapine, Quetiapine

•

+/- Levodopa

•

- DA/Anticholinergic

PD PSP MSA CBD DLB Motor symmetry + +++ +++ - ++ Axial rigidity ++ +++ ++ ++ ++ Tremor +++ - - + + Limb dystonia + + + +++ - Pyramidal signs - + ++ +++ - Apraxia - + - +++ - Postural instability ++ +++ ++ + ++

Vertical supranuclear gaze restriction + +++ ++ ++ -

Frontal behavior + +++ + ++ ++

Visual hallucination + - - + +++

Dysautonomia + - ++ - +

Levodopa response early in course +++ + + - + Levodopa response late in course ++ - + - +