Parkinsonism What makes it different?

Transcription

1 What is Parkinsonism? Parkinsonism What makes it different? Praween Lolekha, MD. MSc. Neurology division, Department of Internal Medicine Thammasat University A motor syndrome with the following cardinal features: Bradykinesia Rest tremor Rigidity Postural instability Flexed posture Freezing or motor blocks Definite 2/6 Probable 1/6 Possible 2/6 Differential diagnosis of Parkinsonism Red flags for Parkinsonism Idiopathic Parkinson s Disease (PD) Secondary parkinsonism - Drug-induced - Vascular parkinsonism - Normal pressure hydrocephalus (NPH) - CNS infection - Metabolic-toxic encephalopathy - Structural lesions - Head trauma Parkinsonism Parkinson-plus syndrome - Progressive supranuclear palsy (PSP) - Corticobasal dengeneration (CBD) - Multiple system atrophy (MSA) - Diffuse Lewy body disease (DLB) Heredodegenerative parkinsonism - Huntington s disease - Wilson s disease (WD) - Neuroacanthocytosis - Neurodegeneration with brain iron accumulation (NBIA) - Spinocerebellar ataxias (2,3,17) - Others Young-onset : Juvenile (genetic) PD Wilson s disease (WD), NBIA Symmetric onset: MSA, PSP, VaP, NPH Absent tremor : Ataxia : MSA, PSP, CBD, VaP, NPH MSA, SCA Pyramidal signs : MSA, PSP, CBD, VaP, NPH Neuropathy : MSA Early postural instability: PSP, MSA, VaP, NPH Red flags for Parkinsonism Secondary 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. Drug-induced parkinsoism Normal pressure hydrocephalus (NPH) Cerebrovascular disease Toxins Trauma 1

2 Drug-induced parkinsonism 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) Cerebrovascular parkinsonism Lower body 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 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 Toxic induced parkinsonism 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 2

3 Infectious and parkinsonism Encephalitis lethargica Von-Economo s disease, 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 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 years old Prognosis ~10 years MSA-P: common in western MSA-C: common in Asia Late stage 28% have all symptoms Cytoplasmic αs-containing inclusions in oligodendroglia 3

4 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 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 Pyramidal symptoms Hyperreflexia Spastic dystonia Extensor plantar response Pseudobulbar palsy REM sleep behavior disorder Obstructive Sleep Apnea (OSA) Pisa syndrome Transverse pontine fibers degeneration Hyposignal in putamen with slit like Hyperintense (iron deposit) 4

5 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 ( mg/day) Dystonia- Botulinum toxin injection Steele-Richardson-Olszewski syndrome Most common parkinson-plus syndrome Prevalence 6-6.4/100,000 Onset years old Prognosis ~10 years Macroscopic pathology Subthalamic nucleus Red nucleus Substantia nigra Pontine tegmentum Striatum Oculomotor nucleus Medulla Dentate nucleus Tufted astrocyte Tau +ve Neurofibrillary tangle 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) 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) 5

6 PSP-Imaging study 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 Penguin sign Morning glory sign Corticobasal Syndrome (CBS) and Corticobasal Degeneration (CBD) Levodopa response ~10-30% in the first 2 years Gait training Prevent falls Botulinum toxin injection +/- Anticholinergic - Dopamine agonists Co enzyme Q10 Cortex + Basal ganglia pathology Corticobasal syndrome (CBS: clinical phenotype) CBD, AD, Pick s disease, PSP, FTD, CJD, PML Corticobasal degeneration (CBD: pathology) Age onset: years old Hyperphosphorylated tau The least common parkinson-plus Corticobasal Syndrome (CBS) 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 Cortical lobe signs Apraxia : limb apraxia, ideomotor apraxia, limbkinetic apraxia, orobuccal apraxia, apraxial of eyelid opening Aphasia, mutism Alien limb (50%) Cortical sensory loss, visual neglect Dementia Disinhibition, agitation, depression, anxiety 6

7 Corticobasal degeneration (CBD) Tau-positive ballooned neuron Asymmetry cortical atrophy Astrocytic plagues Tau accumulation in Cortex Basal ganglia Thalamus Brainstem Dementia with Lewy Bodies (DLB) Levodopa response 20% -Dopamine agonists +Benzodiazepine +Botulinum toxin injection Rx dementia, depression 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 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