PART 4 in Microsoft Office

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Two main mutations: A53T, A30P: promote oligomerization of -synuclein Accounts for 50% of early-onset inherited PD; 20% of sporadic early onset cases Gene is E3 ubiquitin protein ligase; activity is decreased by parkin mutations PET: widespread reductions in dopamine uptake (unlike sporadic PD) Gene is ubiquitin carboxy-terminal hydrolase L1 Mutations decreased recycling of ubiquitin monomers Mitochondrial gene Slow progression; gene plays role in cellular response to oxidative stress Gene is novel kinase Gene is implicated in the formation and identity of dopaminergic neurons

Clinical Features A tetrad of hypo- and bradykinesia, resting tremor, postural instability, and rigidity are the core features of Parkinson disease These are evident as expressionless face, poverty and slowness of voluntary movement, resting tremor, stooped posture, axial instability, rigidity, and festinating gait These manifestations of basal ganglionic disease have been fully described in Chap 4, and only certain diagnostic problems and nuances of the clinical picture need be considered here The early symptoms may be dif cult to appreciate and are often overlooked by family members because they evolve slowly and tend to be attributed to the natural changes of aging The voice becomes soft and monotonous For a long time the patient may not be conscious of the inroads of the disease At rst the only complaints may be of aching of the back, neck, shoulders, or hips and of vague weakness A slight stiffness and slowness of movement or a reduction in the natural swing of one arm during walking are ignored, until one day it occurs to the physician or to a member of the family that the patient has the cast of Parkinson disease Infrequency of blinking, as pointed out originally by Pierre Marie, is often a helpful early sign The usual blink rate (12 to 20 per minute) is reduced in the parkinsonian patient to 5 to 10 per minute, and with it there is a slight widening of the palpebral ssures, creating a stare (Stellwag sign) A reduction in movements of the small facial muscles imparts the characteristic expressionless masked appearance (hypomimia) When seated, the patient makes fewer small shifts and adjustments of position than the normal person (hypokinesia), and the ngers straighten and assume a exed and adducted posture at the metacarpophalangeal joints The characteristic tremor, which usually involves a hand, is often listed as the initial sign; but in at least half the cases, observant family members will already have remarked on the patient s relative immobility and reduction or slowness of movement More-

over, in 20 to 25 percent of cases the tremor is mild and intermittent or evident in only one nger or one hand The tremor of the fully developed case takes several forms, as was remarked in Chap 6 The four-per-second pill-rolling tremor of the thumb and ngers, while most characteristic, is seen in only a proportion of patients and is typically present when the hand is motionless, ie, not used in voluntary movement (hence the term resting tremor) Complete relaxation, however, greatly reduces or abolishes the tremor, and a volitional movement usually dampens it momentarily The rhythmic beat coincides with an alternating burst of activity in agonist and antagonist muscles in the electromyogram (EMG); hence the apt description alternating tremor is also applied The arm, jaw, tongue, eyelids, and foot are less often involved Even the least degree of tremor is felt during passive movement of a rigid part (cogwheel phenomenon, or Negro s sign) The tremor shows surprising uctuations in severity and is aggravated by walking and excitement, but the frequency of the tremor remains constant (Hunker and Abbs) It bears repetition that one side of the body is typically involved before the other, and the classic tremor then remains asymmetrical as the illness advances Lance and associates have called attention to a second common type of tremor in Parkinson disease a ne, seven- to eightper-second, slightly irregular action tremor of the outstretched ngers and hands This tremor, unlike the slower one, persists throughout voluntary movement, is not evident with the limb in a resting position, and is more easily suppressed by relaxation Electromyographically, it lacks the alternating bursts of action potentials seen in the more typical tremor and resembles, if not equates with, essential tremor (page 81, Table 6-1)) It is subject to different medications than those used for the alternating tremor The Parkinson patient may have either type of tremor or both We have been less impressed with rigidity and hypertonus as