Parkinsonism
- General
- Parkinsonism may be primary or secondary to other conditions.
- All result from a relative loss of dopamine mediated inhibition of the effects of acetylcholine in the basal ganglia.
Idiopathic paralysis agitans (IPA) Clinical
- Classical Parkinson’s disease AKA shaking palsy.
- Numbers
- Affects ≈ 1% of Americans > age 50 yrs,
- Frequently underdiagnosed.
- Male: female ratio is 3:2.
- Clinical features
- Classic triad of Parkinson's disease
- Tremor (resting, 4-7/second)
- Rigidity (cogwheel)
- Bradykinesia
- Other signs may include:
- Postural instability,
- Micrographia,
- Mask-like facies.
- Gait
- Of small, shuffling steps (marche á petits pas)
- Festinating gait.
- Non-motor symptoms
- Drooling (reduced swallowing),
- Dementia,
- REM sleep disorders,
- Loss of smell,
- Constipation,
- Mood disorder (especially depression),
- Orthostatic hypotension,
- Bladder and erectile dysfunction
- Other features:
- Unilateral onset
- Progressive disorder
- Excellent L-dopa response
- Pathophysiology
- Degeneration primarily of pigmented (neuromelanin-laden) dopaminergic neurons of the pars compacta of the substantia nigra, → Reduced levels of dopamine in the neostriatum (caudate nucleus, putamen, globus pallidus) →
- Decreases the activity of inhibitory neurons with predominantly D2 class of dopamine receptors, which project directly to the internal segment of the globus pallidus (GPi),
- Increases (by loss of inhibition) activity of neurons with predominantly D1 receptors which project indirectly to the globus pallidus externa (GPe) and subthalamic nucleus.
- The net result is increased activity in GPi which has inhibitory projections to the thalamus → suppresses activity in the supplemental motor cortex among other locations.
- Increased direct pathway increases hyperkinesia
- Increased indirect pathway causes akinesia
- Basal ganglia projections
Pathway | Neurotransmitter | Type |
SNc—striatal direct pathway (nigrostriatal) | Dopamine acting at D1 receptors | Excitatory |
SNc—striatal indirect pathway (nigrostriatal) | Dopamine acting at D2 receptors | Inhibitory |
Striatum—SNr (striatonigral) | GABA (Substance P, dynorphin) | Inhibitory |
Striatum—GPi (striatopallidal) | GABA (Substance P, dynorphin) | Inhibitory |
Striatum—Gpe (striatopallidal) | GABA (Enkephalin) | Inhibitory |
STN—Gpi/SNr (subthalamopallidal/nigral) | Glutamate | Excitatory |
GPi/SNr—thalamus (pallido/nigro-thalamic) | GABA | Inhibitory |
VA/VL—cortex (thalamocortical) | Glutamate | Excitatory |
Cortico-striatal | Glutamate | Excitatory |
- Pathology
- Microscopy
- Lewy bodies (eosinophilic intraneuronal hyaline inclusions) are the hallmark of IPA.
Difference between Parkinson’s and multiple system atrophy
Parkinson’s disease | Multiple system atrophy | |
Synucleinopathy | Synucleinopathy | |
Definition | Bradykinesa with resting tremor or rigidity | Progressive neurodegenerative disorder characterized by a combination of symptoms that affect both the autonomic nervous system (the part of the nervous system that controls involuntary action such as blood pressure or digestion) and movement. |
Clinical features | - Bradykinesia - Rigidity - Tremor (repetitive movement) - Dyskinesia (has rotator component to it) - Acting out dreams | - Adult onset - Progressive - Autonomic failure: urinary incontonence, erectile dysfunction, or orthostatic hypotension - Poorly levodopa responsive Parkinsonism (bradykinesia, rigidity, tremor, postural instability) or cerebellar syndrome (gait ataxia, cerebellar dysarthria, limb ataxia, cerebellar oculomotor dysfunction) |
Pathophysiology | Loss of substantia nigra neurons, which project to the caudate nucleus and putamen, results in depletion of the neurotransmitter dopamine | Unknown cause. ? Prion like spreading of aberrant alpha-synuclein from neuron to glia → glial myelin dysfunction + sti. Inflammation → neurodegeneration Loss of cells in • Putamen, substantia Nigra, caudate nucleus, locus ceruleus, pontine nuclei, intermediolateral cell columns |
Clinically distinguishing IPA from secondary parkinsonism (see below) may be difficult early.
Idiopathic paralysis agitans | 2nd Parkinson | |
Speed of onset | Gradual onset | Rapid onset and progression |
Response to Levodopa | Response well | Equivocal |
Location of early symptoms | Asymmetrical (Bradykinesia + tremor) | Symmetrical/midline symptoms (Ataxia, gait impartment, Sphincter disturbance) |
Presence of other features | None | Such as early dementia, sensory findings, profound orthostatic hypotension, or abnormalities of extraocular movements |
Parkinsons plus (Secondary parkinsons)
- MND
- PSP
- Corticobasal degeneration
Overshooting of eyes due to Cerebellar disease
Eyes cannot follow: smooth pursuit system
Labile emotions; cry then laugh without feeling of sadness. MND
Natural progression
- 3/4 have rest tremor
- Spread to ipsilateral foot I year
- Contralateral limb involvement 2 - 3 yrs
- Many non-motor features
Pathology
- Bragg stage
- Stage 1: The disease begins in structures of the lower brainstem and the olfactory system. In particular, the dorsal motor nucleus of the vagus nerve in the medulla oblongata and anterior olfactory nucleus are affected.
- Stage 2: The pathology spreads to the pons and rhombencephalon
- Stage 3: The pathology spreads to the midbrain and forebrain
- Stage 4: The pathology spreads to the basal portions of the cerebral cortex
- Stage 5: The pathology spreads to the entire cortex
- Stage 6: The pathology spreads to the entire neocortex
- Correlation with clinical symptoms
Clinical grading
- MDS-UPDRS (Movement disorder society-Unified Parkinson's Disease Rating Scale)
- Consists of 4 parts:
- Non-motor experiences of daily living (Part I)
- Motor experiences of daily living (Part II)
- Motor examination (Part III)
- Motor complications (Part IV)
- Used to measure severity of PD
- Higher the score the worse the disability
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