Cases reported "Parkinson Disease"

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11/1120. Missense and silent tau gene mutations cause frontotemporal dementia with parkinsonism-chromosome 17 type, by affecting multiple alternative rna splicing regulatory elements.

    frontotemporal dementia with parkinsonism, chromosome 17 type (FTDP-17) is caused by mutations in the tau gene, and the signature lesions of FTDP-17 are filamentous tau inclusions. Tau mutations may be pathogenic either by altering protein function or gene regulation. Here we show that missense, silent, and intronic tau mutations can increase or decrease splicing of tau exon 10 (E10) by acting on 3 different cis-acting regulatory elements. These elements include an exon splicing enhancer that can either be strengthened (mutation N279(K)) or destroyed (mutation Delta280(K)), resulting in either constitutive E10 inclusion or the exclusion of E10 from tau transcripts. E10 contains a second regulatory element that is an exon splicing silencer, the function of which is abolished by a silent FTDP-17 mutation (L284(L)), resulting in excess E10 inclusion. A third element inhibiting E10 splicing is contained in the intronic sequences directly flanking the 5' splice site of E10 and intronic FTDP-17 mutations in this element enhance E10 inclusion. Thus, tau mutations cause FTDP-17 by multiple pathological mechanisms, which may explain the phenotypic heterogeneity observed in FTDP-17, as exemplified by an unusual family described here with tau pathology as well as amyloid and neuritic plaques. ( info)

12/1120. Immunohistochemical and subcellular localization of Parkin protein: absence of protein in autosomal recessive juvenile parkinsonism patients.

    Autosomal recessive juvenile parkinsonism (AR-JP) is a distinct clinical entity characterized by a selective degeneration of nigral neurons. Recently, the parkin gene responsible for AR-JP has been identified. Now, we report the subcellular localization of Parkin protein in patients with AR-JP or Parkinson's disease (PD) and in controls by immunoblotting and immunohistochemistry using antibodies raised against the Parkin molecule. Parkin protein was absent in all regions of the brains of patients with AR-JP. Parkin protein was not decreased in the brains of sporadic PD patients. Immunoreactivity was detected in a few lewy bodies. Parkin protein was located in both the Golgi complex and cytosol. ( info)

13/1120. Developmental stuttering and Parkinson's disease: the effects of levodopa treatment.

    The effects of dopamine on developmental stuttering was studied in a 44 year old man with developmental stuttering and Parkinson's disease during three levodopa "on" periods and three "off" periods. When compared with the "off" periods, during the "on"' periods he demonstrated an increase of speech dysfluencies. These findings lend support to the dopamine hypothesis of developmental stuttering. ( info)

14/1120. Numerous and widespread alpha-synuclein-negative lewy bodies in an asymptomatic patient.

    lewy bodies (LB) and pale bodies (PB), their putative precursors, can be found in a spectrum of diseases characterized by parkinsonism and/or dementia. Furthermore, LB are occasionally observed in some other neurodegenerative diseases and in normal aging. Classical LB are typically found in the brain stem, especially in the substantia nigra, where these inclusions are associated with neuronal loss and clinical signs of idiopathic Parkinson's disease (PD). The so-called cortical LB occur in the cerebral cortex, amygdala and claustrum with little or no neuronal loss and are clinically associated with dementia in dementia with LB (DLB). We describe a patient without apparent clinical signs of parkinsonism and/or dementia, whose brain contained numerous classical-like LB, pale inclusions with features of PB and transitions between these two. These inclusions had similar immunohistological (ubiquitin positive; neurofilament positive; tau negative) and ultrastructural features as the LB in PD and DLB except for the lack of immunoreactivity for alpha-synuclein. The pons and cerebral cortex showed the highest number of LB, up to 165/1.76 mm2. These numbers were contrasted by the lack of obvious neuronal loss or gliosis. The absence of alpha-synuclein reactivity in the LB in this symptomless patient corroborates the hypothesis that alpha-synuclein accumulation in LB is an important step in neurodegeneration in PD and DLB, but tones down the role of alpha-synuclein in LB formation in general. This patient seems to represent a new variant in the spectrum of diseases associated with LB. ( info)

15/1120. Parallel processing of sensory inputs: an evoked potentials study in Parkinsonian patients implanted with thalamic stimulators.

    In two drug-resistant Parkinsonian subjects, who underwent thalamic chronic stimulation for extrapyramidal symptoms relief, median nerve somatosensory evoked potentials (SEPs) were recorded before and at different times following the thalamic lead implant. In both subjects, a transient obliteration of post-rolandic SEPs components was detected; pre-rolandic waves' amplitude was preserved or showed a tendency to increase after the beginning of chronic stimulation. Parietal waves' amplitude totally recovered pre-surgical values after 1 month. Latency of both pre- and post-central components remained stable. The 'dissociate behaviour' of the examined waves following the thalamic implant reinforces the hypothesis that short-latency sensory inputs are processed by separate and independent routes which are functionally segregated at subcortical level. ( info)

16/1120. Camptocormia (bent spine) in patients with Parkinson's disease--characterization and possible pathogenesis of an unusual phenomenon.

    Camptocormia is characterized by severe forward flexion of the thoracolumbar spine which increases while walking and disappears in the recumbent position. We describe for the first time eight patients with presumed idiopathic Parkinson's disease (mean age 66 /-5 yrs; mean symptom duration 13.1 /-5.1 yrs) who developed camptocormia. This impressive abnormal posture emerged 4-14 years from disease onset, and in some patients stooped posture was the prominent symptom at diagnosis. There was no clear correlation between camptocormia and levodopa treatment. In some patients the camptocormic posture improved, and in others it was unchanged or even aggravated following levodopa administration. Three patients reported worsening of this symptom during "off" periods and also with fatigue. The pathogenesis of this phenomenon is unknown but might represent either a rare type of dystonia or an extreme form of rigidity. ( info)

17/1120. Diffuse lewy body disease presenting as multiple system atrophy.

    OBJECTIVES: The majority of patients with diffuse lewy body disease have cognitive or psychiatric manifestations as part of their initial presentation. A sizable minority present with parkinsonian features alone. Autonomic features may also occur, typically after the development of cognitive changes. We aim to demonstrate that diffuse lewy body disease may rarely also present with parkinsonism accompanied by marked autonomic dysfunction in the absence of significant cognitive or psychiatric abnormalities. methods: Case report based on a retrospective chart review and neuropathological examination. RESULTS: We report on a patient in whom a clinical diagnosis of multiple system atrophy was made based on a presentation of parkinsonism with prominent and early autonomic involvement. The former included postural tremor, rigidity and bradykinesia, while the latter consisted of repeated falls due to orthostasis and the subsequent development of urinary incontinence midway through the course of her illness. She was poorly tolerant of dopaminergic therapy due to accentuated orthostasis. Benefit from levodopa was limited and only evident when attempted withdrawal resulted in increased rigidity. There was no history of spontaneous or drug-induced hallucinations, delusions or fluctuating cognition, and in contrast to the prominence and progression of her parkinsonian and autonomic features over the first several years, cognitive impairment did not occur until the final stages of her illness, seven years after the onset of initial symptoms. Neuropathological examination revealed numerous lewy bodies in both neocortical as well as subcortical structures consistent with a diagnosis of diffuse lewy body disease. There was marked neuronal loss in the substantia nigra as well as the autonomic nuclei of the brainstem and spinal cord. CONCLUSIONS: In addition to cognitive, psychiatric, and parkinsonian presentations, diffuse lewy body disease may present with parkinsonism and prominent autonomic dysfunction, fulfilling proposed criteria for the striatonigral form of MSA. ( info)

18/1120. From off-period dystonia to peak-dose chorea. The clinical spectrum of varying subthalamic nucleus activity.

    The effect of chronic bilateral high-frequency stimulation of the subthalamic nucleus (STN) on levodopa-induced dyskinaesias was investigated in eight patients with fluctuating Parkinson's disease complicated by functionally disabling off-period dystonia. All of the patients also had severe diphasic and peak-dose chorea, so that it was possible to study the effect of high-frequency stimulation on the different types of levodopa-induced dyskinaesias. Off-period fixed dystonia was reduced by 90% and off-period pain by 66%. After acute levodopa challenge, high-frequency stimulation of the STN reduced diphasic mobile dystonia by 50% and peak-dose choreic dyskinaesias by 30%. The effect of bilateral high-frequency stimulation of the STN on the Unified Parkinson's Disease Rating Scale motor score had the same magnitude as the preoperative effect of levodopa. This allowed the levodopa dose to be reduced by 47%. The combination of reduced medication and continuous high-frequency stimulation of the STN reduced the duration of on-period diphasic and peak-dose dyskinaesias by 52% and the intensity by 68%. Acute high-frequency stimulation of the STN mimics an acute levodopa challenge, concerning both parkinsonism and dyskinaesias, and suppresses off-period dystonia. Increasing the voltage can induce repetitive dystonic dyskinaesias, mimicking diphasic levodopa-induced dyskinaesias. A further increase in voltage leads to a shift from a diphasic-pattern dystonia to a peak-dose pattern choreodystonia. Chronic high-frequency stimulation of the STN also mimics the benefit of levodopa on parkinsonism and improves all kinds of levodopa-induced dyskinaesias to varying degrees. Off-period dystonia, associated with neuronal hyperactivity in the STN is directly affected by stimulation and disappears immediately. The effect of chronic high-frequency stimulation of the STN on diphasic and peak-dose dyskinaesias is more complex and is related directly to the functional inhibition of the STN and indirectly to the replacement of the pulsatile dopaminergic stimulation by continuous functional inhibition of the STN. Chronic high-frequency stimulation of the STN allows a very gradual increase in stimulation parameters with increasing beneficial effect on parkinsonism while reducing the threshold for the elicitation of stimulation-induced dyskinaesias. In parallel with improvement of parkinsonism, the levodopa dose can be gradually decreased. As diphasic dystonic dyskinaesias are improved to a greater degree than peak-dose dyskinaesias, both direct and indirect mechanisms may be involved. Peak-dose choreatic dyskinaesias, associated with little evidence of parkinsonism and thus with low neuronal activity in the STN, are improved, mostly indirectly. Fixed off-period dystonia, mobile diphasic dystonia and peak-dose choreodystonia seem to represent a continuous clinical spectrum reflecting a continuous spectrum of underlying activity patterns of STN neurons. ( info)

19/1120. Deterioration in parkinsonism with low-dose pergolide.

    The administration of dopamine agonists can have a role early in the course of Parkinson's disease, in an attempt to reduce the frequency of long-term motor complications associated with the use of levodopa. After treatment with dopamine agonists has begun, gradual dose escalation is recommended to reduce the incidence of side effects; at low doses, parkinsonian symptoms significantly decline in some patients, only to improve as the dose increases. We report a number of such patients and discuss the possible pathogenesis of this motor deterioration. ( info)

20/1120. Treatment with AC pulsed electromagnetic fields improves olfactory function in Parkinson's disease.

    Olfactory dysfunction is a common symptom of Parkinson's disease (PD). It may manifest in the early stages of the disease and infrequently may even antedate the onset of motor symptoms. The cause of olfactory dysfunction in PD remains unknown. Pathological changes characteristic of PD (i.e., lewy bodies) have been demonstrated in the olfactory bulb which contains a large population of dopaminergic neurons involved in olfactory information processing. Since dopaminergic drugs do not affect olfactory threshold in PD patients, it has been suggested that olfactory dysfunction in these patients is not dependent on dopamine deficiency. I present two fully medicated Parkinsonian patients with long standing history of olfactory dysfunction in whom recovery of smell occurred during therapeutic transcranial application of AC pulsed electromagnetic fields (EMFs) in the picotesla flux density. In both patients improvement of smell during administration of EMFs occurred in conjunction with recurrent episodes of yawning. The temporal association between recovery of smell and yawning behavior is remarkable since yawning is mediated by activation of a subpopulation of striatal and limbic postsynaptic dopamine D2 receptors induced by increased synaptic dopamine release. A high density of dopamine D2 receptors is present in the olfactory bulb and tract. Degeneration of olfactory dopaminergic neurons may lead to upregulation (i.e., supersensitivity) of postsynaptic dopamine D2 receptors. Presumably, small amounts of dopamine released into the synapses of the olfactory bulb during magnetic stimulation may cause activation of these supersensitive receptors resulting in enhanced sense of smell. Interestingly, in both patients enhancement of smell perception occurred only during administration of EMFs of 7 Hz frequency implying that the release of dopamine and activation of dopamine D2 receptors in the olfactory bulb was partly frequency dependent. In fact, weak magnetic fields have been found to cause interaction with biological systems only within narrow frequency ranges (i.e., frequency windows) and the existence of such frequency ranges has been explained on the basis of the cyclotron resonance model. ( info)
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