Parkison

Parkison’s Disease Definition Chronic progressive neurological disorder characterised by the presence of bradykinesia with at least one rest tremor or rigidity Risk factors Sporadic idiopathic Most common Age History of familial of PD in younger people Mutations in genes encoding glucocerebrosidase MPTP exposure Chronic metal exposure Male Genetic risk factors PINK-1 GBA DJ-1 TREM2 SNCA PRKN LRRK2 Head trauma Toxin exposure Pesticides Clinical Features Prodromal premotor symptoms Non-specific non motor symptoms May happen up to 7 years before motor symptoms Anosmia Olfactory bulb is one of the first things that get affected Depression/anxiety Aches and pain REM sleep behaviour disorder Autonomic features Urinary urgency Hypotension Constipation Restless leg syndrome Bradykinesia Slow movements Progressive reduction in amplitude of repeated movements Delay in movement initiation Gait freezing Akinesia Resting tremor Unvarying increased resistance within the range of passive movement Stooped or hunched posture Due to rigidity Rigidity Resistance is independent of velocity or direction (unlike spasticity) Throughout entire range of movement Lead pipe Cogwheel Masked facies Hypophonia Hypokinetic dysarthria Micrographia Shuffling gait Due to rigidity and bradykinesia Asymmetrical gait changes Fatigue Neuropsychiatry symptoms Depression, anxiety and psychosis Red Flags Early cognitive changes Rapid progression Poor response to levodopa Atypical symptoms And the other features of DDx Classification Stage Description I Unilateral involvement only II Bilateral involvement without impairment of balance Mid to moderate involvement III Some postural instability Physical independent Severe disability IV Posture imbalance Still can walk without assistance Wheelchair bound or bedridden unless aided V Pathology Hallmark Lewy body neural inclusion Loss of dopaminergic neurons from the pars compacta of the SN in the mid brain Diagnosis Criteria for PD: Bradykinesia and ONE of: Limb rigidity 4 to 6 Hz resting tremor Postural instability does not caused by visual vestibular, cerebellar or proprioceptive dysfunction Differentiation Features suggestive of PD rather than other causes of parkinsonism Features that suggest a diagnosis other than PD Dementia early in the disease course Falls within the first year of diagnosis Early development of severe autonomic dysfunction Urinary incontinence Neurogenic orthostatic hypotension Unliteral resting tremor Other neuro signs such as Excellent response to levodopa Upper motor neuron signs Progressive disorder Vertical gaze palsy Persistent asymmetry of motor symptoms Cerebellar signs Symptom onset coincides with dopamine antagonist treatment No response to 800 to 100 mg per day of levodopa History of repeated strokes with stepwise progression of parkinsonian features Significant vascular disease, cerebellar atrophy of the midbrain or iron or calcium deposition visible on neuroimaging Investigations Mainly a clinical diagnosis Investigations are done when diagnosis is unclear or red flags for other DDx are present DaTscan Most established imaging test Visualises the dopamine system in the brain Radioactive tracer is injected -> attaches to dopamine transporters in the striatum Allows for imaging of the density of dopamine receptors After 3 to 6 hours -> a scan is made to detect tracer present In PD -> reduced signal in the straitum Highly sensitive but cannot different between different types of Parkisonian disorders Skin Bx Tests for abnormal alpha synuclein deposits in peripheral nerves Three Bx Neck, thigh and leg CSF test -> seed amplification assay Detects abnormal alpha synuclein in CSF via amplification techniques Other imaging modalities that may be useful PET scans -> measure glucose metabolism or dopamine production Advanced MRI Transcranial sonography Alpha-synuclein PET Combining imaging methods can provide a more complete diagnosis May do Ix to rule out other DDx Management Levodopa Dopamine precursor -> converted to dopamine in the brain Treatment of choice for motor symptoms Greatest effect on motor symptoms in PD with the least adverse effect Is combined wit dopa-decarboxylase inhibitor E.g. benserazide or capidopa A clear response can take 4 to 8 weeks Most patients on it will eventually develop motor symptom complications. Can be managed using drugs such as entacapone Side effects: Nausea Orthostatic dizziness Somnolence MAO-B inhibitors Anticholinergics E.g. benztropine Usually for prominent rest tremor Careful for elderly and those with cognitive frailty NMDA receptor antagonist Useful for dyskinesia Avoid late in the afternoon or evening due to risk of insomnia Use with caution in people with cardiac failure Side effects: Hallucinations Peripheral oedema Insomnia Livedo reticularis Avoid dopamine blocking anti-emetics Dopamine agonists Can cause behavioural adverse effects E.g. compulsive shopping, eating, hoarding, gambling, sexual preoccupations, non- medical use medicines etc. Do not use in patients with a history of the above and a history or disorders of substance use or addictive behaviours Patients must be advised of those side effects before commencing this class Amantadine For management of levodopa induced dyskinesia For patients with persistent nausea Use domperidone for their nausea 3 times a day for up to 7 days Rapid eye movement sleep behaviour Clonazepam Insomnia Sleep hygiene Amitriptyline Constipation Fibre supplementation Macrogol Psychosis Quetiapine Depression Paroxetine Restless leg syndrome Pramipexole Orthostatic hypotension Increase fluid and salt intake Fludrocortisone Deep brain stimulation Stereotactic insertion of electrodes in the brain In subthalamic nucleus: response is similar to levodopa with reduction in dyskinesia In globus pallidus: improves dyskinesia but levodopa is still required for motor symptoms Thalamus -> tremor only Levodopa intestinal gel infusion For only a select group of patients with severe motor complications Tissue transplantation Mixed results Physiotherapy, occupational therapy and physical aids Complications In later stages may not respond to medications Dementia Severe depression Anxiety Dysphagia and chocking and aspiration pneumonia Pneumonia Falls