Parkinson s Disease
Basal ganglia motor circuit 1 Direct pathway (gas pedal) 2 Indirect pathway (brake) To release or augment the tonic inhibition of GPi on thalamus
Direct pathway There is a tonic inhibition of GP on thalamus Striatum (putamen and caudate) directly inhibit/decrease/release GPi inhibition Result with increase excitatory effect of thalamus on frontal motor area This pathway is medicated by dopamine excitatory effect on D1 receptor of putamen Direct pathway is a gas pedal effect
Indirect pathway GPi tonic inhibit thalamus Striatum indirectly excite GPi through GPe and STN Result with increase GPi inhibition on thalamus The pathway is mediated by inhibitory D2 receptor of putamen Indirect pathway is a brake
Parkinsonism Parkinsonism is a group of symptoms ( syndrome) Parkinsonism is not equal to Parkinson s Disease Think Parkinson s Disease when 1. Asymmetric onset 2. L Dopa responsive 3. Rest tremor 4. Without early fall, cerebellar sign, early dysautonomia
United Kingdom Parkinson's Disease Society Brain Bank Diagnostic Criteria for Parkinson s Disease Step 1: Diagnosis of Parkinsonism Bradykinesia and at least one of the following: Muscular rigidity 4 6 Hz resting tremor Postural instability not caused by primary visual, vestibular, cerebellar or proprioceptive dysfunction Criteria of diagnosis of Parkinson disease (Gelb et al, 1999) commissioned and supported by the Advisory Council of the National Institute of Neurological Disorders and Stroke, US National Institutes of Health.
DaT scan SPECT to detect Dopamine transporter in suspected parkinsonian patient Isotope Ioflupane (Iodine 123) has high affinity to presynapic dopamine transporter in putamen Dopaminergic neuron at the striatum is lost in patient with parkinsonism Usually about 60 % dopaminergic neuron is lost before patient with Parkinson s disease become symptomatic Not specific to Parkinson s disease
Medical treatment of Parkinson s disease
Only treat Tremor Deep brain stimulation L Dopa response symptom Motor fluctuation Dyskinesia No effect on cognitive function and behaviour problem
PROTOCOL FOR DEEP BRAIN STIMULATION FOR PARKINSON S DISEASE Criteria for Candidate 1 Idiopathic Parkinson s disease 1.1 No features of atypical parkinsonism such as cerebellar, ocular, pyramidal or autonomic signs 1.2 Exclude MSA, PSP or DLB 2 Disabling motor complications despite optimized medications 2.1 UPDRS motor > 30/108 at medication off condition 2.2 H&Y > 2.5/5 at medication off condition 2.3 S&E < 70/100 at medication off condition 3 Dopamine responsive 4 Duration of disease: 5 years 5 Age: 75 6 No Significant mental health problem e.g. dementia, depression or active psychosis unrelated to medication 6.1 MMSE 24/30 7 No significant co-morbidity with contraindication to surgery or with limited life expectancy 8 MRI brain reveals no structural lesion, no severe cerebral atrophy or extensive white matter change Pre-op Baseline Assessment and to Confirm Fulfillment of the Criteria: 1 Medication ON/OFF dairy for 7 days by the patient / caregiver 2 UPDRS and levodopa challenge test: 2.1 Full UPDRS (part I IV) 2.2 L-dopa challenge test: 2.2.1 Levodopa 200mg at practically medication Off (12 hours) 2.2.2 Dopamine responsive: 33% decrease in UPDRS part III (motor) scores compared with the score at medication Off condition 3 Psychological assessment (by psychologist) General Cognition MoCA Attention/Working Memory Digit Span Spatial Span Stroop Color Trails test Language Category Fluency Visuoperception Hooper Visual Organization Test Memory CAVLT Benton Visual Retention Abstraction/Reasoning/Planning WCST Mood/Trait/Disposition HADS STAI STDI 4 PD39 5 Psychiatry assessment (clinical consultation for screening of psychiatric disorder) 6 Serum copper and ceruloplasmin, serum manganese 1
Outcome Assessment 1 At 6, 12 and 24 months post-op: 1.1 UPDRS with medication Off and On 1.2 Psychological assessment (same as the protocol for pre-op assessment) 1.3 PD39 References. 1 Defer GL, Widner H, Marie RM et al: Core Assessment Program for Surgical Interventional Therapies in Parkinson s Disease (CAPSIT-PD).Movement Disorder 1999;14(4):572-584 2 Lang AE, MD, Houeto JL, Krack P, et al: Deep Brain Stimulation: Preoperative Issues Movement Disorders 2006; 21(Suppl):S171 S196 3 Gill DJ, Freshman A, Blender JA, Ravina B: The Montreal Cognitive Assessment as a screening tool for cognitive impairment in Parkinson s disease.movement disorders 2008;23(7):1043-1046 4 Mok CTV: Protocol for deep brain stimulation for Parkinson s disease. 2000 (PWH/CUHK movement disorder group) 5 National Collaborating Centre for Chronic Conditions: Parkinson s disease: National clinical guideline for diagnosis and management in primary and secondary care. Royal College of Physicians 2006. www.rcplondon.ac.uk 6 Tsang KL, Chi I, Ho SL, Lou VW, Lee TM, Chu LW: Translation and validation of the standard Chinese version of PDQ-39: a quality-of-life measure for patients with Parkinson's disease. Movement Disorder 2002;17(5):1036 Abbreviation of Assessment scales: 1 H&Y: Hoehn and Yahr Staging Scale 2 MMSE: Mini Mental State Examination [total scores 30] 3 PD39: Quality of life measure for patients with Parkinson s disease 4 S & E: Schwab and England Activity of Daily Livng Scale 5 UPDRS: Unified Parkinson s Disease Rating Scales (HKMDS Meeting 30Jan2009, XLZhu)
Procedure of DBS 1. Frame placement 2. Imaging e.g CT/MRI 3. Selection of target direct or indirect method and planning of trajectory 4. Burr holes for entry 5. Microelectrode recording 6. Electrode stimulation 7. Fixation of electrode 8. Connection of electrodes to extension cable and pulse generator 9. Placement of pulse generator