Cases reported "Parkinson Disease"

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1/78. Transplant of cultured neuron-like differentiated chromaffin cells in a Parkinson's disease patient. A preliminary report.

    BACKGROUND: Treatment of Parkinson's Disease (PD) has been attempted by others by transplanting either the patient's own adrenal medullary tissue or fetal substantia nigra into caudate or putamen areas. However, the difficulties inherent in using the patient's own adrenal gland, or the difficulty in obtaining human fetal tissue, has generated the need to find alternative methods. methods: We report here of an alternative to both procedures by using as transplant material cultured human adrenal chromaffin cells differentiated into neuron-like cells by extremely low frequency magnetic fields (ELF MF). RESULTS: The results of this study show that human differentiated chromaffin cells can be grafted into the caudate nucleus of a PD patient, generating substantial clinical improvement, as measured by the Unified Rating Scale for PD, which correlated with glucose metabolism and D2 DA receptor increases as seen in a PET scan, while allowing a 70% decrease in L-Dopa medication. DISCUSSION: This is the first preliminary report showing that transplants of cultured differentiated neuron-like cells can be successfully used to treat a PD patient.
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2/78. 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.
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3/78. 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.
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4/78. 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.
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5/78. 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.
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6/78. Function of the cerebellum in Parkinsonian rest tremor and Holmes' tremor.

    We describe a patient who developed Parkinson's disease (PD) 17 years after resection of his right cerebellum because of a Lindau tumor. He showed a classic 4.3-Hz resting tremor on the left side but a 3.1-Hz resting, postural, and intention tremor on the right side compatible with midbrain tremor (Holmes' tremor). We conclude that the generator of the tremor in PD cannot be located within the olivocerebellar loop. The cerebellum, however, seems to modulate the tremor frequency of parkinsonian rest tremor and may prevent the rest tremor from transforming into a postural and goal-directed tremor.
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7/78. Postural and action myoclonus in patients with parkinsonian type multiple system atrophy.

    patients with a parkinsonian syndrome and features of multisystem atrophy (pMSA) may exhibit abnormal movements of the hands and fingers, which are reported in the literature either as "jerky" tremor or myoclonus. We studied clinically and electrophysiologically these movements in 11 consecutive patients with pMSA. No abnormal movements were observed when the patients were at complete rest, except for a characteristic parkinsonian "pill-rolling" tremor in one patient. Abnormal small-amplitude, nonrhythmic movements involving just one or a few fingers, or more rarely the whole hand, were observed in nine patients when holding a posture or at the beginning of an action. Accelerometric recordings showed small-amplitude irregular oscillations which, contrary to those of patients with tremor, had no predominant peak in the Fast Fourier frequency spectrum analysis. Electromyographic recordings in the forearm and hand muscles showed brief jerks of less than 100 ms duration which were synchronous in antagonist muscles of the forearm and alternated with brief periods of silence. Electrical stimulation of the digital nerves evoked consistent reflex responses in the wrist flexor and extensor muscles at a latency of 55.3 /-4.1 ms (range, 50-63 ms). Routine electroencephalographic (EEG) and somatosensory evoked potentials to median nerve stimulation were normal. back-averaging of the EEG activity time-locked to the jerks was performed in two patients with no evidence of abnormal cortical activity. Two patients had episodes of transient respiratory failure related to pneumonia. This caused a long-lasting enhancement of the abnormal hand and finger movements, which became larger and more widespread, with features of posthypoxic myoclonus. We conclude that the abnormal hand and finger movements of patients with pMSA are a form of postural and action myoclonus, and can be described as mini-polymyoclonus.
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8/78. Tolcapone and hepatotoxic effects. Tasmar Advisory Panel.

    Four patients with parkinson disease have recently been described in whom severe hepatic dysfunction developed in association with tolcapone therapy. These reports led to the introduction of a "black box" warning and more intensive monitoring requirements in the united states. A review of these cases and all clinical trials indicates that liver dysfunction did not develop in any patient who had received monitoring of liver function according to the original prescribing information. Virtually all instances of liver enzyme abnormality and clinical liver dysfunction occurred within 6 months of initiating treatment. To assess the current role of tolcapone therapy in parkinson disease, a panel of neurologists and hepatologists was convened. consensus was reached with respect to the following: (1) Tolcapone is an effective agent in the treatment of patients with fluctuating parkinson disease. (2) The risk of developing irreversible liver injury is negligible with appropriate monitoring. (3) It may be possible to reduce the frequency of monitoring after 6 months of treatment. (4) The requirement that tolcapone be withdrawn if liver enzymes are elevated above the upper limit of normal on a single occasion is unnecessarily restrictive. It was concluded that tolcapone, when used as an adjunct to levodopa, is an effective anti-parkinsonian agent and that less frequent monitoring after 6 months, with an action limit of 2 to 3 times the upper limit of normal, is sufficient to ensure safety in patients who are deriving benefit from the drug.
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9/78. Use of an implantable cardioverter defibrillator in a patient with two implanted neurostimulators for severe Parkinson's disease.

    We report a patient with Parkinson's disease treated with two pectorally implanted neurostimulators (NSs) who presented with a life-threatening ventricular tachyarrhythmia in whom an abdominal ICD was implanted. Testing during implantation showed that the NS did not affect the bipolar sensing of the ICD, even when the NSs were set at a frequency of 130 pulses/s with an output of 5 V and pulse width of 0.21 ms in a bipolar and a unipolar configuration. The ICD shock, however, did affect both NSs: there was a reset to the output Off state and there was a reset of the electrode polarities.
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10/78. Failure of long-term pallidal stimulation corrected by subthalamic stimulation in PD.

    Bilateral high-frequency continuous stimulation of the internal globus pallidus or subthalamic nucleus constitutes a new therapeutic approach for the treatment of patients with severe PD. The authors report two patients in whom stimulation of the globus pallidus failed to give long-term relief and was successfully replaced by bilateral subthalamic stimulation. The results emphasize the reversibility of deep brain stimulation therapy and suggest that the subthalamic target is preferable to the pallidal target.
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