====== Idiopathic paralysis agitans ======

===== Epidemiology =====

Affects ≈ 1% of Americans >age 50 yrs,
((Mitchell SL, Kiely DK, Kiel DP, et al. The Epidemiology, Clinical Characteristics, and Natural History of Older Nursing Home Residents with a Diagnosis of Parkinson's Disease. J Am Geriatr Soc. 1996; 44:394–399))
it is frequently underdiagnosed.
((Lang AE, Lozano AM. Parkinson's Disease. First of Two Parts. N Engl J Med. 1998; 339:1044–1053))
Male: female ratio is 3:2. Not clearly environmentally or genetically induced, but may be influenced by these factors.

===== Pathophysiology =====

Degeneration primarily of pigmented ([[neuromelanin]]-laden) [[dopaminergic neuron]]s of the [[pars compacta]] of the [[substantia nigra]], resulting in reduced levels of [[dopamine]] in the [[neostriatum]] ([[caudate nucleus]], [[putamen]], [[globus pallidus]]). This decreases the activity of inhibitory neurons with predominantly D2 class of [[dopamine receptor]]s, which project directly to the internal segment of the globus pallidus (GPi), and also increases (by loss of inhibition) activity of neurons with predominantly D1 receptors which project indirectly to the globus pallidus externa (GPe) and subthalamic nucleus
((Kondziolka D, Bonaroti EA, Lunsford LD.
Pallidotomy for Parkinson's Disease. Contemp
Neurosurg. 1996; 18:1–6))

The net result is increased activity in GPi which has inhibitory projections to the thalamus which then suppresses activity in the supplemental motor cortex among other locations.

Histologically: [[Lewy bodies]] (eosinophilic intraneuronal hyaline inclusions) are the hallmark of IPA.

===== Clinical =====

Classical [[Parkinson’s disease]] AKA [[shaking palsy]]. 

Other signs may include postural instability, micrographia, mask-like facies. Gait consists of small, shuffling steps (marche á petits pas) or festinating gait.

===== Differential diagnosis =====

Clinically distinguishing IPA from [[secondary parkinsonism]]: 

May be difficult early. IPA generally exhibits gradual onset of [[bradykinesia]] with [[tremor]] that is often asymmetrical and initially responds well to [[levodopa]]. Other disorders are suggested with rapid progression of symptoms when the initial response to levodopa is equivocal, or when there is early midline symptoms (ataxia or impairment of gait and balance, sphincter disturbance...) or the presence of other features such as early [[dementia]], sensory findings, profound orthostatic hypotension, or abnormalities of extraocular movements
((Koller WC, Silver DE, Lieberman A. An Algorithm for the Management of Parkinson's Disease. Neurology. 1994; 44:S5–52))
((Young R. Update on Parkinson's Disease. Am Fam Physician. 1999; 59:2155–2167)).

===== References =====