Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013362 (dysarthria)
 3,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leigh disease is a subacute neurodegenerative disorder characterized by symmetric necrotic lesions in the basal ganglia, cerebellum, thalamus, brain stem, and optical nerves and caused by altered oxidative phosphorylation. We describe the clinical, biochemical, neuroimaging, and molecular studies of a 19-year-old boy with early-onset Leigh disease manifesting as severe extrapyramidal disorder with generalized dystonia and choreoathetosis. He was born of healthy parents after an uneventful pregnancy and delivery. At the age of 2 1/2 years, after a minor respiratory infection, he developed unstable, broad-based gait and tremor of the hands. These symptoms persisted for the next several years, when ataxia became more prominent. Difficulty in swallowing, dysarthria, trunk dystonia, and marked dyskinesia of the arms and hands gradually developed. Nystagmus, transient ptosis, and strabismus also appeared. Abnormal laboratory findings included elevated plasma and cerebrospinal fluid lactate and pyruvate, with an abnormal lactate/pyruvate ratio. Cranial computed tomography and magnetic resonance imaging demonstrated signs of cerebellar atrophy, bilateral and symmetric hypodensities in the lentiform nucleus and thalamus, and transient hyperintensities of cerebral peduncles in T2-weighted sequences suggestive of Leigh disease. Muscle biopsy revealed isolated fiber atrophy, necrotic fibers undergoing phagocytosis, and no ragged-red fibers. The measured catalytic activity of cytochrome c oxidase in skeletal muscle homogenates demonstrated a partial cytochrome c oxidase deficiency No abnormalities in the mitochondrial genome and in the SURF-1 gene were found. The boy is currently receiving levodopa therapy, creatine monohydrate, and a high dosage of thiamine and lipoic acid, his condition is stabilized, and extrapyramidal symptoms are less pronounced.
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PMID:Cytochrome c oxidase partial deficiency-associated Leigh disease presenting as an extrapyramidal syndrome. 1151 Sep 39

The term acanthocytosis is derived from the Greek for "thorn" and is used to describe a peculiar spiky appearance of erythrocytes. Acanthocytosis is found to be associated with at least three hereditary neurological disorders that are generally referred to as neuroacanthocytosis. Abetalipoproteinaemia is an autosomal recessive condition, characterised by absence of serum apolipoprotein B containing lipoproteins leading to fat intolerance and fat-soluble vitamin deficiency. This results in a progressive spinocerebellar ataxia with peripheral neuropathy and retinitis pigmentosa. Chorea-acanthocytosis is also an autosomal recessive condition and is characterised by chorea, orofaciolingual dyskinesia, dysphagia, dysarthria, areflexia, seizures and dementia. Some of its features, including choreic movements, peripheral neuropathy with areflexia, elevated serum creatine kinase levels and myopathy are shared by another form of neuroacanthocytosis, McLeod syndrome. Patients affected by this X-linked disorder also show abnormal expression of Kell blood group antigens and a permanent haemolytic state. In addition to these cases, acanthocytosis is occasionally associated with other neurological disorders, such as Hallervorden-Spatz disease. For each of the neuroacanthocytosis syndromes we review the main clinical features and their molecular bases. The recent molecular genetics findings are the first step towards the understanding of the pathogenetic mechanisms and eventually the search for effective treatments.
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PMID:Clinical features and molecular bases of neuroacanthocytosis. 1218 48

The introduction of levodopa in the 1960s revolutionised the treatment of Parkinson's disease (PD), and it continues to be the most effective symptomatic therapy. The vast majority of PD patients who start treatment with L-dopa experience good to excellent functional benefit. In vitro studies with high doses of L-dopa and absent glia had shown that it may be neurotoxic, but other tissue culture studies show L-dopa to be neuroprotective. Most studies in animal models and clinico-pathological and mortality studies in humans failed to show evidence in favour of accelerated dopaminergic neuronal loss with long-term L-dopa therapy.L-dopa continues to be beneficial throughout the course of PD, although as the disease progresses, escape of some symptoms from adequate control may occur and refractory disabilities such as impaired balance, dysarthria, cognitive decline and hallucinations may emerge. Treatment of advanced PD may also be complicated by the emergence of motor fluctuations and dyskinesias. Studies in animal models and in humans show that these motor complications are not specific to a particular dopaminergic agent, but that they are related both to the extent of the striatal lesion and to the mode of application of dopaminergic agents: Pulsatile administration of L-dopa and of the dopamine agonist apomorphine causes more motor complications than continuous striatal dopaminergic receptor stimulation, and continuous administration can alleviate existing dyskinesias and fluctuations. Several controlled studies comparing levodopa and dopamine agonists as initial treatment have attempted to answer the question whether delaying L-dopa therapy can reduce the occurrence of motor complications. Three medium-term (3-5 years) and one 10-year study showed less dyskinesia in the first five years of treatment in patients who had started therapy with a dopamine agonist. However, these studies also consistently showed that levodopa provided better functional improvement in the first years of treatment. Ten-year follow-up data in patients randomised to L-dopa or bromocriptine also showed a slightly lower incidence of motor complications in the bromocriptine arm. However, this difference was not significant for the clinically relevant moderate and severe forms of dyskinesias and fluctuations, and was achieved at the expense of significantly worse disability scores during the first years of therapy. Furthermore, the relative impact of motor disability and dyskinesias on patients' quality of life remains to be established. Concordance is essential in the optimum treatment of PD and patients should be informed of the various therapeutic options available. Treatment should respect individual patients' needs and take into account their particular functional disabilities and specific handicaps. Low-dose L-dopa therapy (up to 400 mg/day), however, remains the most effective initial treatment of choice for the majority of patients.
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PMID:Treatment of Parkinson's disease: levodopa as the first choice. 1237 59

We report a 52-year-old Japanese woman who developed dyskinesia, epilepsy, and gait disturbance. She was well until 35 years of age, when she noted the onset of gait disturbance. She also noted abnormal involuntary movements in her limbs. She also noted dysarthria at age 38. A neurologist examined her at age 41. The neurologist found cerebellar ataxia and dyskinesia. The atrophy of the brain stem and the cerebellum was on CT. She started to have generalized convulsion with loss of consciousness. Dementia became apparent at age 40. In October, 1993, she became psychotic in which she behaved violently taking off her clothes shouting as "Fire". She was treated with major tranquilizers and became quiet. However, choreic movements became prominent. Her subsequent course was complicated with dysphagia, dementia, convulsion, and frequent bouts of pneumonia. She expired on January 24, 2000 after developing pneumonia. Her father and one sibling had similar motor disturbances. She was discussed in a neurological CPC. The chief discussant arrived at conclusion that the patient had dentatorubral-pallidoluysian atrophy. Most of the participants agreed with this diagnosis. Postmortem examination revealed that entire brain looked smaller than normal including the brain stem and the cerebellum. The cerebellar dentate nucleus showed loss of neurons and gliosis; glumose degenerations were also seen. The external segment of the pallidum showed neuronal loss and gliosis. The subthalamic nucleus showed gliosis without neuronal loss. A demyelinated focus was found in the pons; the lesion looked similar to central pontine myelinolysis. The cerebral white matters were unremarkable. Other areas were unremarkable. The pathological diagnosis was dentatorubral-pallidoluysian atrophy. The pathologic lesion which might explain her dementia was not apparent.
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PMID:[A 52-year-old woman with dyskinesia, epilepsy and gait disturbance]. 1247 84

Subthalamic stimulation is known to improve tremor, akinesia and rigidity in Parkinson's disease. However, other signs such as hypophonia and swallowing disorders can be relatively resistant to this technique. The effect on dysarthria remains unclear. The aim of this study was to investigate the effects of implantation of electrode and stimulation of the subthalamic nucleus (STN) on parkinsonian dysarthria. Seven patients were prospectively included. Electrodes (Medtronic) were implanted in both STN. The electrode contacts and stimulation parameters were adjusted to provide best relief of symptoms with fewest side effects. Assessment used global scales (Unified Parkinson Disease Rating Scale, UPDRS II and III), dyskinesia scale, exhaustive dysarthria assessment (bucco-facial movements, voice, articulation, intelligibility) and the 'dysarthria' item from the UPDRS III. Evaluations were performed in six conditions: before and three months after surgery (pre-op, post-op) stimulation turned off or on (off-stim, onstim), and without or with a suprathreshold levodopa dose (offdrug, on-drug). Performance level on the UPDRS III significantly improved following electrode implantation and stimulation. For dysarthria, modest beneficial effects were observed on several motor parameters, especially lip movements. Voice mildly improved, especially for the modulation in loudness and pitch. Articulation was not affected. Furthermore, intelligibility was slightly reduced in the on-stimulation condition, especially when patients received levodopa. At an individual level, negative effects on intelligibility were observed in two patients, and this was associated with a discrete increase in facial and trunk dyskinesias, but not with the electrode position or stimulation parameters. In conclusion, surgery had weak effects on dysarthria. Intelligibility can be worsened, especially in the on-drug condition. Thus, adaptation of the stimulation parameters can be difficult.
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PMID:Effects of subthalamic nucleus stimulation on parkinsonian dysarthria and speech intelligibility. 1501 14

We conducted an open label pilot study of the effect of bilateral subthalamotomy in 18 patients with advanced Parkinson's disease. In seven patients, the first subthalamotomy pre-dated the second by 12-24 months ('staged surgery'). Subsequently, a second group of 11 patients received bilateral subthalamotomy on the same day ('simultaneous surgery'). Patients were assessed according to the CAPIT (Core Assessment Program for Intracerebral Transplantation) protocol, a battery of timed motor tests and neuropsychological tests. Evaluations were performed in the 'off' and 'on' drug states before surgery and at 1 and 6 months and every year thereafter for a minimum of 3 years after bilateral subthalamotomy. Compared with baseline, bilateral subthalamotomy induced a significant (P < 0.001) reduction in the 'off' (49.5%) and 'on' (35.5%) Unified Parkinson's Disease Rating Scale (UPDRS) motor scores at the last assessment. A blind rating of videotape motor exams in the 'off' and 'on' medication states preoperatively and at 2 years postoperatively also revealed a significant improvement. All of the cardinal features of Parkinson's disease as well as activities of daily living (ADL) scores significantly improved (P < 0.01). Levodopa-induced dyskinesias were reduced by 50% (P < 0.01), and the mean daily levodopa dose was reduced by 47% at the time of the last evaluation compared with baseline (P < 0.0001). Dyskinesias occurred intraoperatively or in the immediate postoperative hours in 13 patients, but were generally mild and short lasting. Three patients developed severe generalized chorea that gradually resolved within the next 3-6 months. Three patients experienced severe and persistent postoperative dysarthria. In two, this coincided with the patients exhibiting large bilateral lesions also suffering from severe dyskinesias. No patient exhibited permanent cognitive impairment. The motor benefit has persisted for a follow-up of 3-6 years. This study indicates that bilateral subthalamotomy may induce a significant and long-lasting improvement of advanced Parkinson's disease, but the clinical outcome was variable. This variability may depend in large part on the precise location and volume of the lesions. Further refinement of the surgical procedure is mandatory.
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PMID:Bilateral subthalamotomy in Parkinson's disease: initial and long-term response. 1568 66

Most movement disorders, reflecting degenerative disorders, develop in a slowly progressive fashion. Some movement disorders, however, manifest with an acute onset. We wish to give an overview of the management and therapy of those acute-onset movement disorders.Drug-induced movement disorders are mainly caused by dopamine-receptor blockers (DRB) as used as antipsychotics (neuroleptics) and antiemetics. Acute dystonic reactions usually occur within the first four days of treatment. Typically, cranial pharyngeal and cervical muscles are affected. Anticholinergics produce a prompt relief. Akathisia is characterized by an often exceedingly bothersome feeling of restlessness and the inability to remain still. It is a common side effect of DRB and occurs within few days after their initiation. It subsides when DRB are ceased. Neuroleptic Malignant Syndrome is a rare, but life-threatening adverse reaction to DRB which may occur at any time during DRB application. It is characterised by hyperthermia, rigidity, reduced consciousness and autonomic failure. Therapeutically immediate DRB withdrawal is crucial. Additional dantrolene or bromocriptine application together with symptomatic treatment may be necessary. Paroxysmal dyskinesias are childhood onset disorders characterised by dystonic postures, chorea, athetosis and ballism occurring at irregular intervals. In Paroxysmal Kinesigenic Dyskinesia they are triggered by rapid movements, startle reactions or hyperventilation. They last up to 5 minutes, occur up to 100 times per day and are highly sensitive to anticonvulsants. In Paroxysmal Non-Kinesiogenic Dyskinesia they cannot be triggered, occur less frequently and last longer. Other paroxysmal dyskinesias include hypnogenic paroxysmal dyskinesias, paroxysmal exertional dyskinesia, infantile paroxysmal dystonias, Sandifer's syndrome and symptomatic paroxysmal dyskinesias. In Hereditary Episodic Ataxia Type 1 attacks of ataxia last for up to two minutes, may be accompanied by dysarthria and dystonia and usually respond to phenytoin. In Type 2 they can last for several hours, may be accompanied by vertigo, headache and malaise and usually respond to acetazolamide. Symptomatic episodic ataxias can occur in a number of metabolic disorders, but also in multiple sclerosis and Behcet's disease.
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PMID:Diagnosis and management of acute movement disorders. 1620 29

Both posteroventral pallidotomy and pallidal deep brain stimulation (DBS) have a documented effect on Parkinsonian symptoms. DBS is more costly and more laborious than pallidotomy. The aim of this study was to analyse the respective long-term effect of each surgical procedure on contralateral symptoms in the same patients. Five consecutive patients, two women and three men, who at first surgery had a mean age of 64 years and a mean duration of disease of 18 years, received a pallidotomy contralateral to the more symptomatic side of the body. At a mean of 14 months later, the same patients received a pallidal DBS on the side contralateral to the pallidotomy. All patients had on-off phenomena and dyskinesias. There were three left-sided and two right-sided pallidotomies, and, subsequently, two left-sided and three right-sided pallidal DBS. The latest evaluation was performed 37 months (range 22-60) after the pallidotomy and 22 months (range 12-33) after the pallidal DBS. Mean UPDRS motor score pre-operatively was 49 and at last follow-up 33 (32.7% improvement, p<0.05). Appendicular items 20-26 contralateral to pallidotomy remained improved more significantly than contralateral to DBS. Dyskinesia scores were also improved more markedly contralateral to the pallidotomy. Two patients exhibited moderate dysarthria and one patient severe dysphonia following DBS. Symptoms contralateral to the chronologically older pallidotomy, especially dyskinesias, rigidity and tremor, were still more improved than symptoms contralateral to the more recent pallidal DBS, despite numerous post-operative patient visits to optimise stimulation parameters.
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PMID:Pallidotomy versus pallidal stimulation. 1655 82

The safety and efficacy of subthalamic nucleus (STN) deep brain stimulation (DBS) in patients who have had a previous unilateral pallidotomy is not clear. We identified 10 patients (9 male) at the Baylor College of Medicine Parkinson's Disease Center who underwent STN DBS after prior unilateral pallidotomy. Demographics, efficacy as determined by off Unified Parkinson's Disease Rating Scale (UPDRS) part III scores, and levodopa equivalent dosing were analyzed. We then compared these to an age- and sex-matched group of 25 DBS patients who had no prior pallidotomy. After their initial pallidotomy (mean age, 51.8 +/- 10.8 years), the mean UPDRS motor off medicine scores improved from 51.3 +/- 14.3 to 34.9 +/- 12.8, and the UPDRS dyskinesia score improved from 1.8 +/- 1.0 to 0.8 +/- 0.7. Their STN DBS off UPDRS motor scores (mean age, 56.0 +/- 10.2 years) improved by 16.0% from 53.1 +/- 9.7 (range, 42-68) to 44.6 +/- 11.1 (range, 25-67). In contrast, the UPDRS off motor scores in a control group of 25 DBS patients improved by 49.9%, from 49.7 +/- 11.1 to 25.7 +/- 18.9, (16.0% vs. 49.9%; P < 0.001). Changes in UPDRS dyskinesia scores were similar in both groups. AE thought to be related to the STN DBS following pallidotomy included worse dysarthria (three) and worse balance (two). STN DBS patients with prior pallidotomy had less improvement in UPDRS off motor score compared to other STN DBS patients, despite relatively good outcomes immediately after their pallidotomy. This may be partially due to a selection bias, but it may also indicate that prior pallidotomy is a negative predictor of outcome of STN DBS and should be considered in patient selection.
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PMID:Subthalamic deep brain stimulation in patients with a previous pallidotomy. 1667 6

We report the case of a 31-year-old man with bipolar disorder who was on a combination therapy of lithium, lamotrigine and escitalopram. Serum lithium level was within therapeutic range. Cerebellar symptoms such as dysarthria, ataxia, and dyskinesia developed in the patient following the pneumonia. Cerebellar syndrome was most likely due to lithium neurotoxicity, which was associated with additional factors such as acute febrile pneumonia, fever and hyponatremia. The reported case suggests that infections may increase the risk of cerebellar toxicity of lithium, even in the therapeutic doses.
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PMID:Cerebellar syndrome in a patient with pneumonia under lithium treatment: A case report. 1680 24


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