PREFACE The advantages which have been derived from the caution with which hypothetical statements are admitted, are in no instance more obvious than in those sciences which more particularly belong to the healing art. It therefore is necessary, that some conciliatory explanation should be offered for the present publication: in which, it is acknowledged, that mere conjecture takes the place of experiment; and, that analogy is the substitute for anatomical examination, the only sure foundation for pathological knowledge. When, however, the nature of the subject, and the circumstances under which it has been here taken up, are considered, it is hoped that the offering of the following pages to the attention of the medical public, will not be severely censured. 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. The disease is of long duration: to connect, therefore, the symptoms which occur in its later stages with those which mark its commencement, requires a continuance of observation of the same case, or at least a correct history of its symptoms, even for several years. Of both these advantages the writer has had the opportunities of availing himself, and has hence been led particularly to observe several other cases in which the disease existed in different stages of its progress. 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. To delay their publication did not, indeed, appear to be warrantable. The disease had escaped particular notice; and the task of ascertaining its nature and cause by anatomical investigation, did not seem likely to be taken up by those who, from their abilities and opportunities, were most likely to accomplish it. That these friends to humanity and medical science, who have already unveiled to us many of the morbid processes by which health and life is abridged, might be excited to extend their researches to this malady, was much desired; and it was hoped, that this might be procured by the publication of these remarks. Should the necessary information be thus obtained, the writer will repine at no censurewhich the precipitate publication of mere conjectural suggestions may incur: but shall think himself fully rewarded by having excited the attention of those, who may point out the most appropriate means of relieving a tedious and most distressing malady.

An Essay on the Shaking Palsy

Postural deformities are frequent and disabling complications of Parkinson's disease (PD) and atypical parkinsonism. These deformities include camptocormia, antecollis, Pisa syndrome, and scoliosis. Recognition of specific postural syndromes might have differential diagnostic value in patients presenting with parkinsonism. The evidence to date suggests that postural deformities have a multifactorial pathophysiology. Contributing factors include muscular rigidity; axial dystonia; weakness caused by myopathy; body scheme defects due to centrally impaired proprioception; and structural changes in the spine. The relative contribution of these different factors varies between patients and across specific syndromes. Improved understanding of the mechanisms underlying postural deformities in PD might ultimately lead us to more effective management strategies for these disabling and drug-refractory complications.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(11)70067-9.pdf

Postural deformities in Parkinson's disease

The neurotransmitter dopamine (DA) is an important molecule bridging the nervous and immune systems. DA through autocrine/paracrine manner modulates the functions of immune effector cells by acting through its receptors present in these cells. DA also has unique and opposite effects on T cell functions. Although DA activates naive or resting T cells, but it inhibits activated T cells. In addition, changes in the expression of DA receptors and their signaling pathways especially in T cells are associated with altered immune functions in disorders like schizophrenia and Parkinson's disease. These results suggest an immunoregulatory role of DA. Therefore, targeting DA receptors and their signaling pathways in these cells by using DA receptor agonists and antagonists may be useful for the treatment of diseases where DA induced altered immunity play a pathogenic role.

/pdf/the-immunoregulatory-role-of-dopamine-an-update-17bl7k4g1p.pdf

The immunoregulatory role of dopamine: an update.

Object Arachnoid cysts are a frequent finding on intracranial imaging. The prevalence and natural history of these cysts in adults are not well defined. Methods We retrospectively reviewed the electronic medical records of a consecutive series of adults who underwent brain MRI over a 12-year interval to identify those with arachnoid cysts. The MRI studies were reviewed to confirm the diagnosis. For those patients with arachnoid cysts, we evaluated presenting symptoms, cyst size, and cyst location. Patients with more than 6 months' clinical and imaging follow-up were included in a natural history analysis. Results A total of 48,417 patients underwent brain MRI over the study period. Arachnoid cysts were identified in 661 patients (1.4%). Men had a higher prevalence than women (p < 0.0001). Multiple arachnoid cysts occurred in 30 patients. The most common locations were middle fossa (34%), retrocerebellar (33%), and convexity (14%). Middle fossa cysts were predominantly left-sided (70%, p < 0.001). Thirty-f...

Prevalence and natural history of arachnoid cysts in adults.

We evaluated the feasibility and safety of therapy with mesenchymal stem cells (MSCs) through consecutively intra-arterial and three repeated intravenous injections and compared the long-term prognosis between MSC-treated (n=11) and control multiple system atrophy (MSA) patients (n=18). The MSC-treated patients showed significantly greater improvement on the unified MSA rating scale (UMSARS) than the control patients at all visits throughout the 12-month study period. Orthostasis in UMSARS I items and cerebellar dysfunction-related items of UMSARS II items were significantly different in favor of MSC treatment compared to controls. Serial positron emission tomography scan in the MSC-treated group showed that increased fluorodeoxyglucose uptake from baseline was noted in cerebellum and frontal white matters. No serious adverse effects related to MSC therapy occurred. This study demonstrated that MSC therapy in patients with MSA was safe and delayed the progression of neurological deficits with achievement of functional improvement in the follow-up period.

Clinical Pharmacology & Therapeutics (2008); 83, 5, 723–730. doi:10.1038/sj.clpt.6100386

Autologous Mesenchymal Stem Cell Therapy Delays the Progression of Neurological Deficits in Patients With Multiple System Atrophy

Background: Camptocormia is an abnormal flexion of the thoracolumbar spine during standing and walking that abates in the recumbent position. Methods: In a single-centre epidemiological and clinical study, the prevalence of camptocormia in Parkinson disease (PD) and its relationship with the clinical features of PD were investigated. A total of 275 consecutive outpatients were systematically screened for camptocormia with a clinical evaluation. Patients who screened positive for camptocormia were subsequently reassessed by formal goniometric analysis. The demographic and clinical features of the patients with and without camptocormia were then compared. Results: A 6.9% (19/275, 95% CI, 4.2 to 10.6) prevalence of camptocormia was found. Camptocormia was found in patients with more severe PD, as clinically assessed by the Hoehn–Yahr (HY) staging and the motor Unified Parkinson Disease Rating Scale (UPDRS) part III, longer l-dopa treatment duration and greater l-dopa daily dose and presence of DSM-IV dementia. Camptocormia was reported to develop after the clinical onset of PD. No correlation was found between the degree of trunk flexion and age, duration of PD, UPDRS motor score, HY staging, and l-dopa treatment duration and dose. As a risk factor, the study identified previous vertebral surgery. Conclusions: Camptocormia, a relatively common sign in PD seems to be related to the clinical severity of PD.

https://jnnp.bmj.com/content/jnnp/80/2/145.full.pdf

Camptocormia in Parkinson disease: an epidemiological and clinical study

Botulinum neurotoxins have been shown to be a safe and effective therapeutic option for most forms of focal dystonia, and are now considered to provide the best symptomatic treatment in these disorders. However, only a few papers addressed the long-term efficacy and safety of repeated treatments with this drug. This article reviews the data from clinical trials that have assessed the long-term results of botulinum neurotoxin type A (BoNT-A) and type B in the treatment of the different forms of focal craniocervical dystonia, cervical dystonia (CD), blepharospasm, oromandibular, and laryngeal dystonia. Studies on the long-term effects of BoNT-A therapy have demonstrated that the majority of patients comply with this repeated treatment because they experience a positive and stable effect over time. It is still unclear whether in patients with focal dystonia the mean dose of BoNT-A changes over time. In spite of the wide spectrum of side effects reported to be associated with BoNT-A treatment, there is no evidence of specific side effects due exclusively to the long-term use of such drugs. The only exception to these positive long-term findings is the occurrence of a subgroup of patients with CD who fail to maintain a sustained response after the first or second effective treatment, partly owing to the development of neutralizing antibodies against the toxin. Longitudinal studies aimed at defining the risk factors for this abnormal pattern of response to botulinum toxin treatment are currently being conducted.

Efficacy and Safety of Long-term Botulinum Toxin Treatment in Craniocervical Dystonia: A Systematic Review

Cardiovascular dysfunction in untreated Parkinson's disease: A multi-modality assessment.

Multiple system atrophy (MSA) is a sporadic neurodegenerative disease of undetermined aetiology presenting with parkinsonian, autonomic, cerebellar, and pyramidal signs. Despite the lack of any effective therapy to reverse MSA, some of the symptoms may be improved with adequate symptomatic therapies. Medical treatment is largely aimed at mitigating the parkinsonian and autonomic features. The therapeutic results of levodopa therapy in cases of MSA are difficult to interpret because of their variability. Nevertheless, the simple statement that patients with MSA do not respond to levodopa is false. Clinical and pathologically proven series document levodopa efficacy in about 40-60% of patients with MSA and predominant parkinsonian features. Other antiparkinsonian compounds (dopamine agonists, amantadine) may also be employed, but they are not more effective than levodopa. Orthostatic hypotension (OH) can be suspected from the patient s history and subsequently documented in the clinic by measuring lying and standing blood pressure. The diagnosis ideally should be confirmed with additional laboratory tests to determine the cause and evaluate the functional deficit, so as to aid treatment. A number of pharmacological agents with different mechanisms of action have been used in MSA to reduce OH when this is symptomatic. OH can also be alleviated by avoiding aggravating factors, such as the effects of food, micturition, exposure to a warm environment, and physiological diurnal changes, and by using other non-pharmacological strategies. The treatment of the very common genitourinary symptoms (incontinence, retention, impotence) should also be considered in order to improve the quality of life of these patients.

Management of multiple system atrophy: state of the art

Mirror movements (MM) refer to ipsilateral involuntary movements that appear during voluntary activity in contralateral homologous body regions. This study aimed to compare the frequency and distribution of MM in an unselected sample of 274 patients with Parkinson's disease (PD) and 100 healthy subjects, and to check a possible relationship between MM and parkinsonian features. MM of the hand were scored according to the Woods and Teuber scale. The frequency of MM was lower in PD patients than in healthy subjects (29% vs. 71%, P < 0.0001). The distribution of MM also differed in the two groups being often bilateral in healthy subjects, invariably unilateral in PD patients. When parkinsonian signs were unilateral, MM always manifested on the unaffected side; when parkinsonian signs were bilateral, MM manifested on the less affected side. PD patients manifesting MM scored significantly lower on Hohen and Yahr staging than patients without MM. Likewise, there was a significant inverse correlation between the intensity of MM as rated by the Woods and Teuber score and HY staging (r = -0.16, P < 0.01). The low frequency of MM in PD probably relates to the complex interactions between the pathophysiological mechanisms leading to parkinsonian signs and the mechanisms responsible for movement lateralization.

Dorina Tiple

Papers

Camptocormia in Parkinson disease: an epidemiological and clinical study

Efficacy and Safety of Long-term Botulinum Toxin Treatment in Craniocervical Dystonia: A Systematic Review

Cardiovascular dysfunction in untreated Parkinson's disease: A multi-modality assessment.

Management of multiple system atrophy: state of the art

Mirror movements in patients with Parkinson's disease