Parkinson's disease

“ Localization of the atrophy.A. Schematic initial progression of Lewy body deposits in the first stages of Parkinson's Disease, as proposed by Braak and colleagues. B. Localization of the cluster of significant volume reduction in PD compared with HC. The significant cluster located in the medulla oblongata/pons is superimposed as a red blob on the mean normalized anatomical scan of all participants. ”

“ I urge physicians, scientists and government and private agencies concerned with Parkinson's disease to sponsor activities designed to inform every American of the need to continue the struggle and the need of their support. ”

“ Moreover, the intention tremor of such a patient, rather than Parkinson’s disease, suggests multiple sclerosis, of which latter disease, however, there is no other sign. Nor does there seem any evidence that these tremors were of cerebellar, paretic, goitrous, or of any definite toxic origin. On the whole, Meige regards it as a neuropathic manifestation resembling what is found in traumatic neurosis. He believes that there is not sufficient evidence that it is the consequence of any structural change in the nervous system. ”

“ As rigorous a distinction must be drawn between the gestures of chorea and the gesticulations of the sufferer from tic as between the tremor of insular sclerosis and of Parkinson's disease.
In assigning an exact meaning to the term muscular inco-ordination, we cannot do better than quote the remarks of Guinon:
The tabetic who throws his legs to right and left, who as he sits at table cannot carry his spoon to his mouth, furnishes an instance of true motor inco-ordination. ”

“ The key result is the finding of a single significant cluster of white matter volume reduction, overlapping the rostral part of the medulla oblongata and the caudal part of the pons. This finding is consistent with the existence of a common anatomical starting point of PD, in accordance with Braak et al. [10] , [12] , unrelated to the duration of the disease, or the severity in term of motor impairments. This finding is also independent of age, although this factor is known to interact with PD condition [22] . ”

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“ PD clinical diagnosis is particularly prone to errors [1] , [2] , as this array of motor symptoms is also present in a wide range of other parkinsonian conditions such as progressive supranuclear palsy, dementia with Lewy bodies, and multiple system atrophy. Confirmation of the diagnosis is often brought by disease progression and the response of patients to levodopa medication. ”

“ In senility, chorea, and Parkinson's disease, the tremors are incessant and continue even when the body is in a state of repose; in sclerosis, goitre, and chronic inebriety they accompany voluntary movements, and in this case they are easily detected by making the patient lift the tip of his finger to his nose or a filled glass to his lips. The nearer the hand approaches its goal, the more intense the oscillations become. Above all, the examiner should not fail to ask the patient to put out his tongue. ”

“ We recruited 23 PD patients at Hoenn and Yahr stages I to II of the disease and 18 healthy controls (HC) matched for age. T1-weighted anatomical scans were acquired (MPRAGE, 1 mm3 resolution) and analyzed using an optimized VBM protocol to detect white and grey matter volume reduction without spatial a priori. When the HC group was compared to the PD group, a single cluster exhibited statistical difference (p<0.05 corrected for false detection rate, 4287 mm3) in the brain stem, between the pons and the medulla oblongata. ”

“ For each group, bold line shows the median, central box includes the middle 50% of the data, and tails of the boxplot show the minimum and maximum values. We ran additional analyses to assess the effect of age in the tested population. No cluster of significant atrophy survived at the threshold used. At last, we ran analyses specific to the PD groups, using age, gender, UPDRS-III score and duration of the disease (expressed as the time elapsed between the first neurological diagnosis and the MRI acquisition) as covariates, and found no atrophy patterns. ”

“ In conclusion, to our knowledge, this is the first study demonstrating that conventional T1-weighted 3 T MRI scans can validate in vivo, on a group basis, the first stages of Braak's model [10] – [12] , This key finding, based on conventional MRI scans easily acquired in clinical practice, could define a critical marker of the disease, in association with other biomarkers, for the diagnosis of PD when initial symptomatology appears, but also presymptomatically as other related symptoms occurs, such as autonomic dysfunctions [29] , RBD [13] , or anosmia [30] . ”

“ Since VBM analysis is a conservative method, as no a priori region of interest is studied, we postulate that damage in this region is common to all patients while the regional evolution of the neurodegenerative process may be more variable across PD patients, and hence lowers the sensibility of white matter VBM analysis in other brain regions. It is also likely that later stages of the disease affect grey matter more significantly but in a more heterogeneous way. ”

“ The patient was a lad about seventeen, who at that time had laboured under this extraordinary disease for more than twelve years. His body was so distorted, and the legs and arms so twisted round it, by the continued convulsive working, that no words can give an adequate idea of the oddity of his figure; the agitation of the muscles was perpetual; but in general he did not complain of pain nor sickness ”

“ By these repeated observations, he hoped that he had been led to a probable conjecture as to the nature of the malady, and that analogy had suggested such means as might be productive of relief, and perhaps even of cure, if employed before the disease had been too long established. He therefore considered it to be a duty to submit his opinions to the examination of others, even in their present state of immaturity and imperfection. ”

“ As slow as is the progress of the disease, so slow in all probability must be the period of the return to health. In most cases, especially in those in which the disease has been allowed to exist long unopposed, it may be found that all that art is capable of accomplishing, is that of checking its further progress. ”

“ By the nature of the symptoms we are taught, that the disease depends on some irregularity in the direction of the nervous influence; by the wide range of parts which are affected, that the injury is rather in the source of this influence than merely in the nerves of the parts; by the situation of the parts whose actions are impaired, and the order in which they become affected, that the proximate cause of the disease is in the superior part of the medulla spinalis; and by the absence of any injury to the senses and to the intellect, that the morbid state does not extend to the encephalon. ”

“ As time and the disease proceed, difficulties increase: writing can now be hardly at all accomplished; and reading, from the tremulous motion, is accomplished with some difficulty. Whilst at meals the fork not being duly directed frequently fails to raise the morsel from the plate: which, when seized, is with much difficulty conveyed to the mouth. At this period the patient seldom experiences a suspension of the agitation of his limbs. ”

“ Lewy bodies have been historically considered as the hallmark of the disease [25] , and more recently, their presence in the substantia nigra has been proposed to correlate with the motor scores of the UPDRS [26] . However, recent progresses in molecular biology and histo-immunology suggest that alpha-synuclein deposits, which constitute the main part of Lewy bodies, involve other cerebral structures than those latter, including the pons and the medulla oblongata, and that it should be considered as a more direct measure of PD pathology and clinical symptomatology [27] . ”

“ Treating of a disease resulting from an assemblage of symptoms, some of which do not appear to have yet engaged the general notice of the profession, particular care is required whilst endeavouring to mark its diagnostic characters. It is sufficient, in general, to point out the characteristic differences which are observable between diseases in some respects resembling each other. But in this case more is required: it is necessary to show that it is a disease [28] which does not accord with any which are marked in the systematic arrangements of nosologists ”

“ D. Western blot analysis shows that 5-HT failed to counteract the effect of dopamine on Akt activity in the presence of dopamine. All other conditions are the same as previously described in Figs. 3–5. Discussion Dopamine has a net inhibitory effect on mitochondrial movement in hippocampal neurons Dopamine is an important neurotransmitter in the regulation of many aspects of neural function. Changes in levels of dopamine, as well as in the dynamic activity of mitochondria, have been implicated in the onset of symptoms in both Parkinson's disease and schizophrenia [11] , [12] . ”

“ Palsy, either consequent to compression of the brain, or dependent on partial exhaustion of the energy of that organ, may, when the palsied limbs become affected with tremulous motions, be confounded with this disease. In those cases the abolition or diminution of voluntary muscular action takes place suddenly, the sense of feeling being sometimes also impaired. But in this disease, the diminution of the influence of the will on the muscles comes on with extreme slowness, is always accompanied, and even preceded, by agitations of the affected parts, and never by a lessened sense of feeling. ”

“ The disease, respecting which the present inquiry is made, is of a nature highly afflictive. Notwithstanding which, it has not yet obtained a place in the classification of nosologists; some have regarded its characteristic symptoms as distinct and different diseases, and others have given its name to diseases differing essentially from it; whilst the unhappy sufferer has considered it as an evil, from the domination of which he had no prospect of escape. ”

“ Experiment has not indeed been yet employed to prove, but analogy certainly warrants the hope, that similar advantages might be derived from the use of the means enumerated, in the present disease. It is obvious, that the chance of obtaining relief will depend in a great measure on the period at which the means are employed. As in every other disease, so here, the earlier the remedies are resorted to, the greater will be the probability of success. ”

“ But in this disease there is one circumstance which demands particular attention; the long period to which it may be extended. One of its peculiar symptoms, Scelotyrbe festinans, [61] may not occur until the disease has existed ten or twelve years, or more; hence, when looking for the period, within which our hopes of remedial aid is to be limited; we may, guided by the slow progress of the malady, extend it to a great length, when compared with that within which we should be obliged to confine ourselves in most other diseases. ”

“ II. A propensity to bend the trunk forwards, and to pass from a walking to a running pace.
This affection, which observation seems to authorise the being considered as a symptom peculiar to this disease, has been mentioned by few nosologists: it appears to have been first noticed by Gaubius, who says, “Cases occur in which the muscles duly excited into action by the impulse of the will, do then, with an unbidden agility, and with an impetus not to be repressed, accelerate their motion, and run before the unwilling mind. ”

“ The term Shaking Palsy is evidently inapplicable to the first of these cases, which [31] appears to have belonged more properly to the genus Convulsio, of Cullen, or to Hieranosos of Linnæus and Vogel [10] .
The latter appears to be referable to that class of proteal forms of disease, generated by a disordered state of primæ viæ, sympathetically [32] affecting the nervous influence in a distant part of the body. ”

“ As the disease proceeds towards its last stage, the trunk is almost permanently bowed, the muscular power is more decidedly diminished, and the tremulous agitation becomes violent. The patient walks now with great difficulty, and unable any longer to support himself [8] with his stick, he dares not venture on this exercise, unless assisted by an attendant, who walking backwards before him, prevents his falling forwards, by the pressure of his hands against the fore part of his shoulders. ”

“ Hitherto the patient will have experienced but little inconvenience; and befriended by the strong influence of habitual endurance, would perhaps seldom think of his being the subject of disease, except when reminded of it by the unsteadiness of his hand, whilst writing or employing himself in any nicer kind of manipulation. But as the disease proceeds, similar employments are accomplished with considerable difficulty, the hand failing to answer with exactness to the dictates of the will. Walking [5] becomes a task which cannot be performed without considerable attention. ”