Various Forms Of Parkinsonism Research Articles

Gastrointestinal disturbances in various forms of parkinsonism

One of the non-motor autonomic disorders of parkinsonism is gastrointestinal disorders, which depend on the form and stage of the disease. To examine the types of gastrointestinal disorders in parkinsonism, depending on the form of the disease. 103 patients with PD were examined, of them primary parkinsonism was 51, secondary parkinsonism was 44, tertiary parkinsonism was 8. The average age of patients was from 33 to 65 years (mean age 46.7 ± 8.1 years). The diagnosis was made according to special criteria that can be differentiated. All patients had various gastrointestinal disorders, according to the type of discomfort after eating, hypersolivation and defecation. Evaluated on the scale UPDRS. After our careful analysis, the results show that with Parkinson's disease, discomfort after eating is 2.1 ± 1.4 points, hypersolivation 0.85 ± 2.2 points and defecation 1.5 ± 1.4 points. In secondary parkinsonism, discomfort after eating is 1.5 ± 1.7, hypersolivation - 0.9 ± 2.1, and defecation 1.8 ± 1.6 points. When at tertiary parkinsonism, this data is 1.8 ± 1.8–0.76 ± 1.7 - 1.2 ± 2.5 points. The total points for PD are 5.4, for secondary parkinsonism 2.51 and for tertiary parkinsonism 4.5 points. After eating and parkinsonism more bowel movements. Gastrointestinal disturbances of the type of discomfort after eating, hypersolivation and defecation depend on the form of parkinsonism. With the help of these disorders it is possible to differentiate the forms and course of the disease.Gastrointestinal disturbances may be a predictor of Parkinson's disease, which can be observed in preclinical manifestations.

Banisteriopsis caapi, a Forgotten Potential Therapy for Parkinson's Disease?

Banisteriopsis caapi, a liana indigenous to the Amazon basin with metagnomigenic properties and possible anti-depressant effects is one of the natural sources of harmala alkaloids. A summary of early trials with extracts of Banisteriopsis caapi and Peganum harmala (from which harmine was first isolated) in the 1920s and 1930s on various forms of parkinsonism is given as well as a brief overview of the known pharmacological properties of harmine. Despite its earlier abandonment because of perceived weaker efficacy than solanaceous alkaloids like scopolamine and hyoscine we propose that harmine should be reconsidered as a potential rapidly acting anti-Parkinsonian agent.

PARK2 Mediates Interleukin 6 and Monocyte Chemoattractant Protein 1 Production by Human Macrophages

Leprosy is a persistent infectious disease caused by Mycobacterium leprae that still affects over 200,000 new patients annually. The host genetic background is an important risk factor for leprosy susceptibility and the PARK2 gene is a replicated leprosy susceptibility candidate gene. The protein product of PARK2, Parkin, is an E3 ubiquitin ligase that is involved in the development of various forms of Parkinsonism. The human macrophage is both a natural host cell of M. leprae as well as a primary mediator of natural immune defenses, in part by secreting important pro-inflammatory cytokines and chemokines. Here, we report that down-regulation of Parkin in THP-1 macrophages, human monocyte-derived macrophages and human Schwann cells resulted in a consistent and specific decrease in interleukin-6 (IL-6) and monocyte chemoattractant protein 1 (MCP-1/CCL2) production in response to mycobacteria or LPS. Interestingly, production of IL-6 at 6 hours by THP-1 cells stimulated with live M. leprae and M. bovis BCG was dependent on pretreatment with 1,25-dihydroxyvitamin D3 (VD). Parkin knockdown in VD-treated cells blocked IL-6 induction by mycobacteria. However, IκB-α phosphorylation and levels of IκB-ξ, a nuclear protein required for IL-6 expression, were not affected by Parkin silencing. Phosphorylation of MAPK ERK1/2 and p38 was unaffected by Parkin silencing while JNK activation was promoted but did not explain the altered cytokine production. In a final set of experiments we found that genetic risk factors of leprosy located in the PARK2 promoter region were significantly correlated with M. leprae sonicate triggered CCL2 and IL6 transcript levels in whole blood assays. These results associated genetically controlled changes in the production of MCP-1/CCL2 and IL-6 with known leprosy susceptibility factors.

Differentiation between Parkinson disease and other forms of Parkinsonism using support vector machine analysis of susceptibility-weighted imaging (SWI): initial results

To diagnose Parkinson disease (PD) at the individual level using pattern recognition of brain susceptibility-weighted imaging (SWI). We analysed brain SWI in 36 consecutive patients with Parkinsonism suggestive of PD who had (1) SWI at 3 T, (2) brain (123)I-ioflupane SPECT and (3) extensive neurological testing including follow-up (16 PD, 67.4 ± 6.2 years, 11 female; 20 OTHER, a heterogeneous group of atypical Parkinsonism syndromes 65.2 ± 12.5 years, 6 female). Analysis included group-level comparison of SWI values and individual-level support vector machine (SVM) analysis. At the group level, simple visual analysis yielded no differences between groups. However, the group-level analyses demonstrated increased SWI in the bilateral thalamus and left substantia nigra in PD patients versus other Parkinsonism. The inverse comparison yielded no supra-threshold clusters. At the individual level, SVM correctly classified PD patients with an accuracy above 86 %. SVM pattern recognition of SWI data provides accurate discrimination of PD among patients with various forms of Parkinsonism at an individual level, despite the absence of visually detectable alterations. This pilot study warrants further confirmation in a larger cohort of PD patients and with different MR machines and MR parameters.

Clinical Differential Diagnosis of Parkinsonism

Several clinical diagnostic criteria are available for differentiating Parkinson’s disease from the various forms of parkinsonism, but most clinical features have inadequate sensitivity and positive predictive value in the differential diagnosis of these conditions. Although a diagnosis of Parkinson’s disease can be a simple clinical exercise in typical patients with a positive response to dopaminergic treatment, the differential diagnosis versus other parkinsonian disorders can be challenging in some cases, particularly early in the disease. In this paper we have reviewed the motor and nonmotor clinical features that are helpful in the differential diagnosis of the most common forms of parkinsonism. A correct diagnosis in a parkinsonian patient is not simply an academic exercise, but it is crucial for planning any possible therapeutical intervention.

A definition of Parkinson's disease

We are now entering a period when the process of unraveling the puzzles of ‘Parkinson's Disease’ has generated a mass of information that does not fit into our traditional concepts. Having split off ‘Progressive Supranuclear Palsy’ and ‘Multiple System Atrophy’, we are faced with the dilemma of what to do with the various forms of Parkinsonism caused by a number of different mutations, and how to interpret pathological heterogeneity. Faced with these new questions, it is time to reconsider how ‘Parkinson's Disease’ is to be defined.

Novel alpha-synuclein-immunoreactive proteins in brain samples from the Contursi kindred, Parkinson's, and Alzheimer's disease.

A specific mutation (A53T) in the encoding region for alpha-synuclein has been identified in a large multigenerational family with an autosomal dominant parkinsonism known as the Contursi kindred. In this study, we used a monoclonal antibody directed against alpha-synuclein in order to identify novel proteins in the brain of an affected member of this kindred who had come to autopsy. Homogenates from the frontal cortex and caudate nucleus were examined using Western blot techniques and compared to matched autopsy specimens from control subjects and patients with various forms of parkinsonism. Western blots, using a 15-min exposure time, revealed the expected 19-kDa band representing alpha-synuclein in all brain samples examined. However, a novel band in the 36-kDa range was also present in the Contursi brain which was not seen in cortex or caudate from control brains or in frontal cortex from 14 cases of typical Parkinson's disease. With a 24-h exposure time, this band was faintly seen in the caudate nucleus of three of the Parkinson's disease cases. Surprisingly, the 36-kDa band (as well as other high-molecular-weight bands) was also present in frontal cortex and caudate nucleus in 3 additional cases that met diagnostic criteria for both Parkinson's disease and Alzheimer's disease. A preliminary analysis of samples from the frontal cortex of 10 Alzheimer's disease cases revealed a 36-kDa band in only one instance. The identification of novel alpha-synuclein-immunoreactive bands in these various forms of parkinsonism may open new research avenues for exploring the relationship between abnormal protein deposition in the brain and one or more neurodegenerative disorders, including the Contursi form of familial parkinsonism.

The Use of Pet in Parkinsons-Disease

Activation studies with positron emission tomography (PET) have provided an understanding of the pathophysiology of akinesia and tremor in Parkinsons disease (PD). [F-18]6-fluoro-L-dopa (FD)-PET and dopamine receptor imaging by PET can assist in the differential diagnosis of various forms of parkinsonism. FD-PET is capable of detecting subclinical dopaminergic deficits. This allows not only the early or preclinical detection of PD but also the investigation of subclinical lesions of the substantia nigra in PD-related disorders. Longitudinal studies of PD and MPTP induced parkinsonism have provided new insight into the pathogenesis of PD.

Neurophysiological investigations of the features of the state and physiological activity of some structures of the striopallidum and thalamus in various forms of parkinsonism.

The results of many years of investigations of the features of the functional state and physiological activity of some structures of the striopallidum (Cd, GP, Put) and thalamus (VP, VL, CM) as links in the brain systems of the organization of mental and motor activity in patients with various forms of parkinsonism are presented in generalized form. The possibilities for the use of various types of ultraslow physiological processes to study the brain mechanisms of the activational and emotional states, with more precise definition of the role of structures of the striopallidal complex in the formation of systems supporting these types of mental activity in parkinsonism, are reviewed.

A year's experience of L-DOPA in the treatment of Parkinson's disease.

206 patients with Parkinson's disease have been treated with oral L-DOPA for periods ranging from three to twelve months. Marked or very marked improvement of bradykinesia, rigidity and tremor occurred respectively in 58.3%, 34.7% and 15% of the cases at the 3rd month of treatment; in 70.8%, 47.7% and 20% at the 6th month (80 cases); in 88%, 64.4% and 16.2% at the 9th month (34 cases). The degree of independence gained in overall behavioural performance has been recorded at three-monthly intervals and reported for the various forms of Parkinsonism (idiopathic 133 cases; arteriosclerotic 39 cases; postencephalitic 34 cases). About 78% of the patients experienced side-effects; all of them were reversible and not very important.

Stereotactic surgery for the relief of Parkinson's disease: Part 1. A critical review

A critical review of the literature dealing with the pathology of the various forms of Parkinsonism and with experimental studies concerning the mechanism of tremor and rigidity is presented. Some recent reports on biochemical defects in Parkinson's syndrome are summarised. The development of surgical methods in the treatment of Parkinsonism is outlined, with emphasis on the evolution of stereotactic procedures. The results reported from surgical lesions in various parts of the basal ganglia, and the means of creating these lesions are discussed. Several series of autopsied cases have demonstrated that the therapeutic lesion is not always accurately sited in the elected target. The indications and contraindications for surgical treatment in Parkinsonism are mentioned. Reports of several large series of basal ganglia operations are reviewed and the effects of pallidal and thalamic lesions are compared, with particular reference to bilateral procedures. The incidence of reported postoperative complications is analysed in detail. This review confirms that correctly placed surgical lesions in the ventrolateral nucleus of the thalamus can arrest tremor and rigidity in the majority of patients, while only a slight beneficial effect on akinesia and defects of postural equilibrium can be achieved. Clinical, anatomical and physiological observations derived from stereotactic operations on the basal ganglia justify the assumption that the sensorimotor or premotor cortex may be significantly involved in the pathology of Parkinson's disease.

Five-year study of benztropine (cogentin) methanesulfonate; outcome in three hundred two cases of paralysis agitans.

• Benztropine, a synthetic drug with anticholinergic, antihistaminic, and sedative actions, was administered by mouth to 302 patients with various forms of Parkinsonism. The drug was found to have peripheral curariform effects that are long-lasting, cumulative, and very useful. Doses of 5 to 10 mg. thrice daily caused excessive flaccidity, to the extent that a patient was unable to lift his arm or raise his head off the pillow. Best results, in the control of rigidity, contracture, tremor, and insomnia, were obtained in the dosage range of 1 to 4 mg. a day for older patients and 2 to 8 mg. a day for younger ones. Abnormalities of gait, which troubled 56 patients, were alleviated in 35 of these. Three case histories are given to illustrate the relief from insomnia, night cramps, rigidity, and tremor, the recurrence of symptoms when the drug was temporarily withdrawn, the safety of continued use for more than five years, and the possibility of obviating side-effects, when they do occur, by simultaneous administration of phenindamine and trihexyphenidyl.