Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied 45 non-demented patients with Parkinson's disease (PD), 12 with progressive supranuclear palsy (PSP), 10 with multiple system atrophy (MSA) and 12 with neuroleptic-induced parkinsonism (NIP) for the presence of apraxia. Our aim was to determine whether a standard comprehensive assessment of different praxic functions would demonstrate specific types of errors not attributable to bradykinesia, rigidity, tremor or any other abnormal elementary motor deficit. PD patients on chronic levodopa treatment were examined in the 'on' and 'off' (treatment) states. Based on apraxia assessment scores, bilateral ideomotor apraxia for transitive movements was found in eight (75%) and 12 (27%) of PSP and PD patients, respectively. Ideomotor apraxia was mainly characterized by spatial errors (i.e., external and internal configuration, body-part-as-object and trajectory). Four PSP but no PD patients exhibited ideomotor apraxia for intransitive movements. PSP as well as PD patients with ideomotor apraxia also had difficulties in imitating hand and finger postures, but none of them failed on pantomime comprehension and pantomime recognition/discrimination. Some PSP patients exhibited, in addition, a limbkinetic type of apraxia and a minority of them displayed deficits on tasks involving multiple steps. Neither MSA nor NIP patients showed any disturbance of praxic functions. There were no differences in age, disease duration, Mini Mental State Examination (MMSE), Unified Parkinson's disease Rating Scale and Hoehn-Yahr scores between apraxic and non-apraxic PD patients, and ideomotor apraxia scores were similar in the 'on' and 'off' states. A correlation was found between ideomotor apraxia scores in PD patients and deficits in frontal lobe-related neuropsychological tasks such as the Tower of Hanoi, verbal fluency and the Trail Making Test. Furthermore, PD patients with apraxia showed higher Hamilton depression scores than non-apraxic PD patients. In PSP patients, ideomotor apraxia scores correlated significantly with cognitive deficit as measured with MMSE. The presence or absence of cortical involvement, and its severity and distribution might determine the presence and type of apraxia in PD and PSP. Apraxia in these conditions would therefore reflect combined cortico-striatal dysfunction.
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PMID:Apraxia in Parkinson's disease, progressive supranuclear palsy, multiple system atrophy and neuroleptic-induced parkinsonism. 905 99

At present, there are three major surgical approaches to Parkinson's disease (PD): (1) Ablative surgery (i.e. pallidotomy, thalamotomy); (2) deep brain stimulation (DBS) of the thalamus, internal globus pallidus (GPi) and subthalamic nucleus (STN); and (3) grafting fetal mesencephalic cells into the striatum. As a result of increasing understanding of the pathophysiology of the basal ganglia and the demonstration of surgical alleviation of experimental parkinsonism, surgery has regained a paramount importance in the management of PD. The aim of pallidotomy and DBS is to reduce the excessive inhibitory output from the GPi and substantia nigra reticulata (SNr). Pallidotomy and DBS of the STN or GPi aim to reverse the pathophysiological consequences of dopamine deficiency in PD, and should be considered entirely symptomatic treatments. The ideal candidates for pallidotomy are young patients in good general health in whom dyskinesias are the main reasons for disability. Patients with severe bilateral problems uncontrollable with present pharmacological tools are candidates for DBS. As yet, there are no formal data to help decide how to choose between GPi and STN stimulation. In our practice, patients are allocated to GPi stimulation when 'on' dyskinesias are extremely severe. In most other instances, we prefer to perform STN stimulation. At present there is almost no reason to decide for the thalamic stimulation since tremor is equally arrested by STN stimulation, which in addition improves all other features of PD. Equally the only indication for thalamotomy would be a patient with long-standing tremor as the main clinical manifestation, which can not be controlled with drugs. The proportion of patients in whom the thalamus will be the preferable target for either DBS or thalamotomy is small (less than 5%). Grafting aims to repair the nigrostriatal pathway and restore dopaminergic function in the striatum. In the future implants containing not only dopaminergic cells but also growth factors and a variety of other substances could become a method to not only functionally compensate the biochemical abnormalities of PD but also to arrest its progression. This technique is limited to a few centres around the world owing to the technical, logistical and ethical problems of obtaining and handling embryonic cells. At present, grafting of dopaminergic cells is perhaps best suited for patients with young-onset PD (less than 45 years old) who are at high risk of developing complications within a short time of beginning pharmacological treatment and in whom the idea of making lesions or implanting electrodes into the brain for decades seems less appealing. Consideration of surgery in any given patient should be weighed against the risks (about 1% mortality and 2-6% of severe morbidity-hemiplegia, cognitive deficit, speech problems, etc.) associated with these techniques. The development of better imaging methods and the growing expertise of multidisciplinary teams will undoubtedly make surgery for PD safer and more effective in the future.
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PMID:Surgical treatment of Parkinson's disease. 942 72

Substance abuse through the deliberate inhalation of petrol (petrol sniffing or gasoline sniffing) is prevalent in inner-urban and remote rural communities. Although acute toxic encephalopathy is a well-documented consequence of petrol sniffing, the neurological and cognitive effects of chronic petrol sniffing are unknown. A structured neurological examination and the Cambridge Neuropsychological Test Automated Battery (CANTAB) were used to assess neurological and cognitive function in 33 current-sniffers (individuals who had sniffed petrol for >6 months), 30 ex-sniffers (individuals who had sniffed petrol in the past but had abstained for 6 months) and 34 matched non-sniffers (individuals who had never sniffed petrol). No subject was, or had been, encephalopathic from petrol sniffing and all were residing in their community. Blood lead and hydrocarbon levels and information about petrol sniffing behaviour were obtained from each subject. When compared with non-sniffers, current-sniffers showed higher rates of abnormal tandem gait, rapid alternating hand movements, finger to nose movements, postural tremor, bilateral palmomental reflexes and brisk deep reflexes. Cognitive deficits occurred in the areas of visual attention, visual recognition memory and visual paired associate learning. Ex-petrol sniffers showed higher rates of abnormal tandem gait and bilateral palmomental reflexes and cognitive deficits in the areas of visual recognition memory and pattern-location paired associate learning. Blood lead levels and length of time of petrol sniffing correlated significantly with the magnitude of neurological and cognitive deficits. Blood hydrocarbon levels were not related to neurocognitive deficits, although this may have been due to methodological difficulties in obtaining hydrocarbon levels. These results suggest that subtle neurological and cognitive abnormalities do occur in individuals who abuse petrol but who do not have acute toxic encephalopathy and that the severity of these abnormalities is reduced with abstinence.
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PMID:Neurological and cognitive abnormalities associated with chronic petrol sniffing. 979 46

The beneficial effects of ventral intermediate nucleus (VIM) stimulation were evaluated in 20 patients with tremor refractory to medical therapy. Thalamic stimulation is a non-ablative procedure which has the advantage of a reversible, non-destructive lesion. Eleven patients [7 with Parkinson's disease (PD) and 4 with essential tremor (ET)] received unilateral VIM implantation, while 9 patients had staged bilateral VIM implantation (4 with PD, 5 with ET). PD patients showed a significant improvement in contralateral arm and leg rest tremor and ipsilateral leg rest tremor (p < 0.02) at a mean follow-up period of 16.2 +/- 7.0 months. Patients with PD did not demonstrate any significant decrease in medication use at follow-up. ET patients demonstrated significant improvement in postural and action tremor in the contralateral arm (p < 0.001), but no significant improvement in the contralateral leg tremor at follow-up. Significant improvements were also seen in ET patients in the Clinical Rating Scale for Tremor (p < 0.001) with respect to several activities of daily living at a mean follow-up of 14.9 +/- 8. 1 months. Deep brain stimulation is a safe and effective treatment for severe tremor refractory to medications. It is a highly effective, reversible, adaptable, and predictable procedure which avoids the complication of cognitive deficit seen in patients with bilateral thalamotomies.
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PMID:Deep brain stimulation of the ventral intermediate nucleus of the thalamus for control of tremors in Parkinson's disease and essential tremor. 1064 Sep 20

A late onset neurological syndrome in carriers of premutation in FMR1 gene was recently described. The condition was named fragile-X-associated tremor/ataxia syndrome (FXTAS) and includes intentional tremor, cerebellar ataxia, parkinsonism, and cognitive deficit. We ascertained the contribution of FMR1 premutation to the phenotypes ataxia, tremor and/or parkinsonism. Sixty-six men over 45 years old presenting these symptoms, isolated or combined, were tested. Also, 74 normal men, randomly chosen in the population, formed the control group. In the patient group, no premutation carrier was found, which is in agreement with other observed frequencies reported elsewhere (0-5% variation). No significant differences were found when comparing gray zone allele frequencies among target and control groups. The FXTAS contribution in patients with phenotypic manifestations of FXTAS was 15/748 (2%). The presence of gray zone alleles is not correlated with FXTAS occurrence.
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PMID:Frequency of FMR1 premutation in individuals with ataxia and/or tremor and/or parkinsonism. 1827 22

Gait disorders form part of the axial symptoms observed in Parkinson's disease (PD) and also represent a major source of therapeutic failure in the later stages of PD, with the appearance of freezing of gait (FOG) and falls. Double-blind clinical trials and, above all, clinical experience have demonstrated that l-DOPA is effective in reducing FOG. Dopaminergic agonists appear to be less effective than l-DOPA and lack formal proof of their efficacy. The enzyme inhibitors provide modest benefits, which need to be confirmed. Hence, these symptoms appear to be partially doparesistant and justify investigation of other major neurotransmission systems. Of the various drugs with partial noradrenergic activity, methylphenidate may improve FOG and attention disorders. Memantine has shown some value in improving motor symptoms and gait in fluctuating parkinsonian patients - possibly by reducing the effect of glutamatergic hyperactivation of the subthalamic nucleus on the pedunculopontine nucleus (PPN). The PPN's dense cholinergic innervation also suggests that cholinesterase inhibitors may be of use, although any benefits must be set against a potential aggravation of rest tremor. The many interactions between the serotoninergic and dopaminergic systems require the implementation of clinical studies on the complex motor impact of serotoninergic treatments, which may aggravate the parkinsonian syndrome while improving gait (as is the case with paroxetine and ritanserin). This review seeks to develop the various pathophysiological hypotheses prompted by the results of fundamental studies and pilot clinical trials, with a view to justifying the implementation of confirmatory, double-blind, placebo-controlled therapeutic trials.
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PMID:[Pharmacological hypotheses and therapeutic strategies for gait disorders in Parkinson's disease]. 1981 97

Progressive cognitive deficits are common in patients with fragile X-associated tremor/ataxia syndrome (FXTAS), with no targeted treatment yet established. In this substudy of the first randomized controlled trial for FXTAS, we examined the effects of NMDA antagonist memantine on attention and working memory. Data were analyzed for patients (24 in each arm) who completed both the primary memantine trial and two EEG recordings (at baseline and follow-up) using an auditory "oddball" task. Results demonstrated significantly improved attention/working memory performance after one year only for the memantine group. The event-related potential P2 amplitude elicited by non-targets was significantly enhanced in the treated group, indicating memantine-associated improvement in attentional processes at the stimulus identification/discrimination level. P2 amplitude increase was positively correlated with improvement on the behavioral measure of attention/working memory during target detection. Analysis also revealed that memantine treatment normalized the P2 habituation effect at the follow-up visit. These findings indicate that memantine may benefit attentional processes that represent fundamental components of executive function/dysfunction, thought to comprise the core cognitive deficit in FXTAS. The results provide evidence of target engagement of memantine, as well as therapeutically relevant information that could further the development of specific cognitive or disease-modifying therapies for FXTAS.
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PMID:Memantine Improves Attentional Processes in Fragile X-Associated Tremor/Ataxia Syndrome: Electrophysiological Evidence from a Randomized Controlled Trial. 2689 32