Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 73-year-old African American female presented to our clinic with painful lower extremity lesions of 2 weeks duration. She was in her usual state of health until 3 months prior to presentation when she reported symptoms of fatigue and weakness. She also noticed an enlarging mass on the left side of her neck. She denied fevers, chills, night sweats or cough. Her symptoms were unresponsive to a course of oral dicloxacillin. The neck mass enlarged over 8 weeks and she was referred to our institution for evaluation. CT scan of the neck showed an enlarged lymph node. Ten days prior to her presentation in dermatology, a fine needle aspirate of the enlarging lymph node revealed necrotizing granulomas. Tissue was sent for routine mycobacterial and fungal cultures. Routine blood work, chest radiograph, and a tuberculin skin test were also performed. At the time of her dermatology visit she described the development of multiple new painful, non-pruritic lesions, bilaterally on the lower extremities. She also reported a red crusted area that appeared at the site of her tuberculin test that was placed subsequent to the development of her lower extremity lesions. Her past medical history was significant for Parkinson's disease, hypothyroidism and hypertension. Her current medications included l-thyroxine, estrogen and diltiazem. Her travel history was only remarkable for a trip to Jamaica the previous spring. She was born and raised in Haiti. She reported a history of a positive tuberculin skin test 20 years ago, but received no therapy. Physical examination revealed a 2 x 3 centimeter firm, nontender left lateral neck mass (Fig. 1). Her right forearm revealed an erythematous, ulcerated, indurated plaque 1.5 cm in diameter (Fig. 2.). Her lower extremities revealed tender 0.5 to 1 cm erythematous nodules below the knees bilaterally (Fig. 3). A punch biopsy of a lower extremity nodule revealed a mild pervisacular dermal infiltrate. Within the subcutaneous tissue there was septal widening. There was also a lymphohistiocytic infiltrate with a slight admixture of neutrophils within the septa of the fat lobules. There was no evidence of necrotizing vasculitis or collagen necrosis. An acid-fast stain was not performed. The histologic findings were consistent with a diagnosis of erythema nodosum. Her laboratory evaluation including CBC, electrolytes, thyroid studies, angiotensin converting enzyme level and chest radiograph were normal. Approximately 1 week after her dermatological evaluation, the fine-needle aspirate culture grew Mycobacterium tuberculosis. A diagnosis of tuberculous lymphadenitis associated with erythema nodosum was confirmed. The patient was started on quadruple therapy of isoniazid, rifampin, ethambutol and pyrazinamide. Her lower limb skins lesions rapidly resolved over the subsequent month and her neck mass also diminished in size. She completed 6 months of antituberculous therapy with complete resolution of her lymphadenopathy.
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PMID:Erythema nodosum associated with reactivation tuberculous lymphadenitis (scrofula). 1201 Mar 45

In the UK, around 10-12 in every 10,000 people have multiple sclerosis, typical features of which include weakness, ataxia, spasticity and sensory loss. By comparison, around 16-18 in every 10,000 have Parkinson's disease, a condition typified by rigidity, bradykinesia, tremor and postural instability. Both conditions can limit function with, for example, nearly 25% of patients with multiple sclerosis and about 10% of those with Parkinson's disease being dependent on a wheelchair. Physiotherapy is widely used as part of a multidisciplinary approach to the management of multiple sclerosis, while 7-38% of people with Parkinson's disease are referred for physiotherapy. Here, we review the evidence for physiotherapy in the management of patients with either condition.
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PMID:MS, Parkinson's disease and physiotherapy. 1205 30

We report on a 63-year-old man with idiopathic Parkinson's disease who developed kyphosis and a severe forward flexion of the thoracolumbar spine. A typical feature was an increase during walking or standing and it completely disappeared in the supine position, mimicking the clinical phenomenon of camptocormia (bent spine). In addition to the abnormal posture, a weakness of the erector spinal muscles, local pain, reddening, and elevated temperature of the paraspinal muscles were evident. Creatine kinase was initially elevated, electromyography showed spontaneous activity and a myopathic pattern. Magnetic resonance imaging and bioptic examinations revealed a focal myositis of the paraspinal muscles. This case indicates that camptocormia can be mimicked by focal myositis of paraspinal muscles and must be included in the differential diagnosis, especially when additional symptoms as inflammatory signs or weakness are present.
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PMID:Camptocormia in Parkinson's disease mimicked by focal myositis of the paraspinal muscles. 1211 14

THALAMUS: The human thalamus is a nuclear complex located in the diencephalon and comprising of four parts (the hypothalamus, the epythalamus, the ventral thalamus, and the dorsal thalamus). The thalamus is a relay centre subserving both sensory and motor mechanisms. Thalamic nuclei (50-60 nuclei) project to one or a few well-defined cortical areas. Multiple cortical areas receive afferents from a single thalamic nucleus and send back information to different thalamic nuclei. The corticofugal projection provides positive feedback to the "correct" input, while at the same time suppressing irrelevant information. Topographical organisation of the thalamic afferents and efferents is contralateral, and the lateralisation of the thalamic functions affects both sensory and motoric aspects. Symptoms of lesions located in the thalamus are closely related to the function of the areas involved. An infarction or haemorrhage thalamic lesion can develop somatosensory disturbances and/or central pain in the opposite hemibody, analgesic or purely algesic thalamic syndrome characterised by contralateral anaesthesia (or hypaesthesia), contralateral weakness, ataxia and, often, persistent spontaneous pain. BASAL GANGLIA: Basal ganglia form a major centre in the complex extrapyramidal motor system, as opposed to the pyramidal motor system (corticobulbar and corticospinal pathways). Basal ganglia are involved in many neuronal pathways having emotional, motivational, associative and cognitive functions as well. The striatum (caudate nucleus, putamen and nucleus accumbens) receive inputs from all cortical areas and, throughout the thalamus, project principally to frontal lobe areas (prefrontal, premotor and supplementary motor areas) which are concerned with motor planning. These circuits: (i) have an important regulatory influence on cortex, providing information for both automatic and voluntary motor responses to the pyramidal system; (ii) play a role in predicting future events, reinforcing wanted behaviour and suppressing unwanted behaviour, and (iii) are involved in shifting attentional sets and in both high-order processes of movement initiation and spatial working memory. Basal ganglia-thalamo-cortical circuits maintain somatotopic organisation of movement-related neurons throughout the circuit. These circuits reveal functional subdivisions of the oculomotor, prefrontal and cingulate circuits, which play an important role in attention, learning and potentiating behaviour-guiding rules. Involvement of the basal ganglia is related to involuntary and stereotyped movements or paucity of movements without involvement of voluntary motor functions, as in Parkinson's disease, Wilson's disease, progressive supranuclear palsy or Huntington's disease. The symptoms differ with the location of the lesion. The commonest disturbances in basal ganglia lesions are abulia (apathy with loss of initiative and of spontaneous thought and emotional responses) and dystonia, which become manifest as behavioural and motor disturbances, respectively.
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PMID:Functional anatomy of thalamus and basal ganglia. 1219 99

Dystonias are frequently observed in Parkinson's disease or other parkinsonian syndromes. They can occur during off-periods, either in the morning (early morning dystonia) or during daily off-periods, and during on-periods. Dystonia involves more frequently the upper and lower limbs, the neck or the face. Dystonia can be painful in particular off-period feet dystonia. The mechanisms underlying dystonia are not fully understood, basal ganglia activity and levodopa levels seems to play an important role. There are several medical options to try and improve those dystonias, adjustment of levodopa doses, adding a dopamine agonist drug, anticholinergics, lithium, baclofene or clonazepam. Those options are not always very effective. Botulinum toxin injections are an alternative treatment for focal dystonia. Muscles have to be selected by observation of the dystonia. Deep muscles in particular in the legs can be injected under EMG guidance. Botulinum toxin injections are particularly helpful and safe for lower limb dystonia. They can be used also for other forms of dystonia. Upper limb dystonia can be injected, allowing more comfort and easier hygiene but not necessarily better function, weakness is the main side effect. Cervical dystonia, blepharospam and oromandibular dystonia can be managed the same way as idiopathic dystonia. The dose might be lower since the muscles are usually not as hypertrophic. Side effects are as expected dysphagia and neck weakness in case of cervical dystonia, ptosis, inocclusion and diplopia in case of blepharospasm, jaw opening difficulty with oromandibular dystonia. Basal ganglia surgery can also help dystonia in a selected population of parkinsonian patients.
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PMID:[Parkinsonian dystonia]. 1461 83

Both constipation and fecal incontinence are prominent lower gastrointestinal tract (LGIT) dysfunctions that occur frequently in multiple system atrophy (MSA). We investigated the mechanism of constipation and fecal incontinence in MSA. Colonic transit time (CTT), sphincter electromyography (EMG), and rectoanal videomanometry were performed in 15 patients with MSA (10 men, 5 women; mean age, 63.5 years; mean duration of disease, 3 years; decreased bowel frequency [< 3 times a week] in 9; difficulty in expulsion in 11; fecal incontinence in 3) and 10 age-matched healthy control subjects (7 men and 3 women; mean age, 62 years; decreased bowel frequency in 2; mild difficulty in expulsion in 2; fecal incontinence in none). Compared to the control subjects, MSA patients had significantly prolonged CTT in the rectosigmoid segment and total colon. Sphincter EMG showed neurogenic motor unit potentials in none of control subjects but in 93% of MSA patients. At the resting state, MSA patients showed a lower anal squeeze pressure (external sphincter weakness) and a smaller increase in abdominal pressure on coughing. During rectal filling, MSA patients showed smaller amplitude in phasic rectal contraction, which was accompanied by an increase in anal pressure that normally decreased, together with leaking in 3 patients. During defecation, most MSA patients could not defecate completely and had larger postdefecation residuals. MSA patients had weak abdominal strain, smaller rectal contraction on defecation, and larger anal contraction on defecation (paradoxical sphincter contraction on defecation), although these differences were not statistically significant. These findings in MSA patients were similar to those in Parkinson's disease patients in our previous study, except for the sphincter denervation and weakness in MSA. Constipation in MSA most probably results from slow colonic transit, decreased phasic rectal contraction, and weak abdominal strain, and fecal incontinence results from weak anal sphincter due to denervation. The responsible sites for these dysfunctions seem to be both central and peripheral nervous systems that regulate the LGIT.
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PMID:Colonic transit time, sphincter EMG, and rectoanal videomanometry in multiple system atrophy. 1530 Jun 57

A 79-year-old woman, with Parkinson's disease treated with cabergoline, was admitted to a hospital due to jaundice and weakness. She was found confused, absent minded, and died after 2 weeks. Autopsy showed an extrahepatic bile duct adenocarcinoma with spread to the gall bladder, the liver, and regional lymphnodes. While cleaning the hospital bed after her death, the nurses found several tablets hidden in the bed. Biological samples obtained at the autopsy were screened for common drugs and narcotics. Several drugs such as buprenorphine, codeine, paracetamol, and propranolol were detected in the blood at therapeutic levels. A method to determine cabergoline in whole blood and other forensic matrices was developed, and further investigations determined cabergoline concentrations in whole blood and liver tissue of 94 and 3100 microg/kg, respectively. The blood concentration was 100 times above the therapeutic level reported on cabergoline in plasma and in combination with her symptoms, suggest she took a fatal overdose of cabergoline.
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PMID:A fatal overdose of the ergot derivative cabergoline. 1548 21

Neurological disorders in humans can be modeled in animals using standardized procedures that recreate specific pathogenic events and their behavioral outcomes. The development of animal models of Parkinson's disease (PD) is important to test new neuroprotective agents and strategies. Such animal models of PD have to mimic, at least partially, a Parkinson-like pathology and should reproduce specific features of the human disease. PD is characterized by massive degeneration of dopaminergic neurons in the substantia nigra, the loss of striatal dopaminergic fibers and a dramatic reduction of the striatal dopamine levels. The formation of cytoplasmic inclusion bodies (Lewy bodies) in surviving dopaminergic neurons represents the most important neuropathological feature of PD. Furthermore, the massive striatal dopamine deficiency causes easily detectable motor deficits in PD patients, including bradykinesia, rigidity, and resting tremor, which are the cardinal symptoms of PD. Over the years, a broad variety of experimental models of PD were developed and applied in diverse species. This review focuses on the two most common "classical" toxin-induced PD models, the 6-hydroxy-dopamine (6-OHDA model) and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model. Both neurotoxins selectively and rapidly destroy catecholaminergic neurons, whereas in humans the PD pathogenesis follows a progressive course over decades. This discrepancy reflects one important and principal point of weakness related to most animal models. This review discusses the most important properties of 6-OHDA and MPTP, their modes of administration, and critically examines advantages and limitations of selected animal models. The new genetic and environmental toxin models of PD (e.show $132#g. rotenone, paraquat, maneb) are discussed elsewhere in this "special issue."
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PMID:Classic toxin-induced animal models of Parkinson's disease: 6-OHDA and MPTP. 1550 55

Alpha-Synuclein is a major component of Lewy bodies, neuronal inclusions diagnostic for Parkinson's disease (PD). While an Ala53Thr mutation in alpha-synuclein can cause PD in humans, in mice the wildtype residue at position 53 is threonine, indicating that mice are either too short-lived to develop PD, or are protected by the six other amino acid differences between the proteins in these two species. Mice carrying an Ala53Thr human SNCA transgene driven by the mouse prion promoter show a mild movement disorder and only rarely develop severe pathology by 2 years of age. To determine whether the presence of mouse alpha-synuclein affects the pathogenicity of the human protein, the transgene was crossed into mice lacking endogenous alpha-synuclein. Mice that express only human alpha-synuclein developed a neuronopathy characterized by limb weakness and paralysis with onset beginning at 16 months of age. The neuronopathy is probably due to high levels of expression of the transgene in the ventral spinal cord leading to motor neuron damage and Wallerian degeneration of the ventral roots. These data suggest mouse alpha-synuclein is protective against the deleterious effects of the human mutant protein.
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PMID:Exacerbated synucleinopathy in mice expressing A53T SNCA on a Snca null background. 1558 43

Exposure to agricultural insecticides, together with yet incompletely understood predisposing genotype/phenotype elements, notably increase the risk of Parkinson's disease. Here, we report findings attributing the increased risk in an insecticide-exposed rural area in Israel to interacting debilitating polymorphisms in the ACHE/PON1 locus and corresponding expression variations. Polymorphisms that debilitate PON1 activity and cause impaired AChE overproduction under anticholinesterase exposure were strongly overrepresented in patients from agriculturally exposed areas, indicating that they confer risk of Parkinson's disease. Supporting this notion, serum AChE and PON1 activities were both selectively and significantly lower in patients than in healthy individuals and in carriers of the risky polymorphisms as compared with other Parkinsonian patients. Our findings suggest that inherited interactive weakness of AChE and PON1 expression increases the insecticide-induced occurrence of Parkinson's disease.
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PMID:Acetylcholinesterase/paraoxonase interactions increase the risk of insecticide-induced Parkinson's disease. 1562 87


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