Acute dystonia

Acute dystonia is a side effect of antipsychotic medication; it nearly always develops a few weeks after the start of a dopamine-blocking agent or substantial increase of the dosage. Acute dystonia is characterized as a syndrome of sustained muscle contractions, frequently causing twisting and repetitive movements or abnormal postures. The risk of acute dystonia depends greatly on the presence of risk factors: early age, male sex, use of cocaine, a history of acute dystonia, and use of a highly potent antipsychotic agent in a normal dosage. The mechanism underlying acute dystonia is unknown: both increase and decrease of the striatal dopamine transmission have been put forward as possible causes. Acute dystonia may also be caused by dopamine-blocking agents that are used not as antipsychotic medication but, for instance, as anti-emetics. Anticholinergic agents are extremely efficacious in treatment as well as prevention of acute dystonia. Prophylaxis of acute dystonia is indicated for patients belonging to the risk groups.     

Value of orally administered retard morphine for therapy of severe pulmonary emphysema of the pink-puffer type. A pilot study

BACKGROUND AND OBJECTIVE: In severe "pink puffer" emphysema the patients' physical capacity is limited by dyspnoea despite maximal application of established treatment. This pilot study investigated the effect of retarded morphine, taken orally for 10 days, on ventilation, dyspnoea, walking capacity and wakefulness. PATIENTS AND METHODS: Twenty clinically stable patients (11 men, 9 women, mean age 68.5 [50-81] years) with "pink puffer" emphysema were studied over a period of 10 days in a prospective, non-controlled trial of cross-over design. Criteria for inclusion in the study were: 1-second forced expiratory volume (FEV1) < 1 I, vital capacity < 50% and normocapnia. In addition to their existing therapy patients received either no further therapy or retarded morphine. Morphine dosage was increased to maximally 3 x 30 mg daily, depending on effectiveness and side effects, dyspnoea at rest and immediately after a 6-min walk (assessed with Borg's visual analog scale), maximal walking capacity were determined, as well as blood gases, respiratory minute volume and the respiratory drive (airway occlusion pressure [P0.1]), responsiveness of the respiratory pathways to CO2 and wakefulness (concentration, fatigue, interest in surroundings). RESULTS: Twelve patients completed the study (group A). In the remaining patients (group B) the test had to be stopped prematurely because of undesirable side effects or an exacerbation of the underlying infection. In group A, morphine (mean dosage: 49.2 +/- 28.4 mg/d) caused a reduction of PaO2, dyspnoea on activity, the resting minute respiratory volume, respiratory drive and CO2 response, and an increase in PaCO2, HCO3- and the 6-min walking distance. Morphine did not produce a change in subjectively evaluated vigilance and the blood pH. CONCLUSION: After strict patient selection oral morphine produced a reduction of exercise dyspnoea and an increase in walking capacity in half of the patients with severe pulmonary emphysema. There also occurred a slight rise in PaCO2 without any relevant respiratory acidosis or significant decrease in wakefulness.     

The common marmoset (Callithrix jacchus) as a model for neuroleptic-induced acute dystonia

To examine whether acute dystonia is induced by neuroleptic treatment, common marmosets were treated with haloperidol orally twice a week over 25 weeks until dystonic behavior was elicited. Movement disorders such as acute dystonia were observed 6 weeks after the initial treatment, and had appeared in all treated animals by 25 weeks. Once these movement disorders were induced, they consistently reappeared after further treatment with haloperidol, and once haloperidol dosing was discontinued, the episodes vanished. Then, various neuroleptic drugs (bromperidol, chlorpromazine, risperidone thioridazine, sulpiride, tiapride, and clozapine) or a nonneuroleptic drug (diazepam) were administered orally instead of haloperidol in the above animals. All the neuroleptic drugs except for clozapine elicited similar abnormal behavior, while diazepam failed to induce any dystonia. An anticholinergic drug, trihexyphenidyl, which is known to reduce acute dystonia in patients, was also given orally to the above haloperidol-sensitized animals, followed by further treatment with haloperidol 30 min later. This clearly suppressed the induction of dystonia by haloperidol. The similarity between these findings for haloperidol-pretreated common marmosets and clinical findings suggests that the present model is useful for predicting the potential of antipsychotics to induce acute dystonia in humans.     

Rapid assay of plasma brain natriuretic peptide in the assessment of acute dyspnoea

AIM: Recognition of heart failure may be difficult in patients presenting with acute dyspnoea, particularly in the presence of chronic airways obstruction or obesity. In a previous study of patients with acute dyspnoea, we showed that the measurement of plasma brain natriuretic peptide (BNP)-a hormone secreted in increased amounts by the failing heart-accurately distinguishes heart failure from primary lung disorder. The aim of the present study was to develop a rapid assay for BNP and evaluate its diagnostic use in patients acutely hospitalised for increasing dyspnoea of any cause. METHODS: A rapid assay for plasma BNP, providing results within 24 h of blood collection, was developed without loss of precision. The results of the rapid and previously established BNP assays were highly correlated (r = 0.9). To determine the diagnostic value of the rapid assay, measurements were undertaken on the day of admission in 123 breathless patients (mean age 68.3, range 23 to 90 years) and related to conventional diagnostic assessments and final outcome. RESULTS: In patients diagnosed and treated urgently for clinical heart failure, plasma BNP was significantly higher (115 (SE 13) pmol/L, n = 39) than in those without clinical heart failure (33 (5) pmol/L, n = 84, p < 0.001). Using a cut-off of 50 pmol/L for the presence of heart failure, there was discordance between BNP level and clinical diagnosis in 21 of 123 cases. Reassessment after independent analysis of discordant cases increased the difference in BNP level in the presence (123 (13) pmol/L, n = 43) or absence (24 (1.5) pmol/L, n = 80) of heart failure. Using two way analysis of variance, no further improvement in discrimination was found when chest radiographs were used together with the BNP data. CONCLUSION: Rapid BNP assays are practicable and provide accurate information on cardiac status-superior to chest radiographs in many cases-early in the course of the patient's presentation with acute dyspnoea.     

Intensive medical monitoring with transesophageal echocardiography in fulminant pulmonary embolism

HISTORY AND FINDINGS: A 60-year-old man underwent a continence-preserving anterior rectal resection for a high rectal carcinoma. After mobilisation on the 5th postoperative day dyspnoea and cyanosis suddenly developed requiring emergency intubation and mechanical ventilation. INVESTIGATIONS: His heart rate was 160/min, blood pressure 80/50 mmHg, mean pulmonary artery pressure by indwelling catheter was 70 mmHg. The electrocardiogram had the classical signs of acute right-heart overload. Transoesophageal echocardiography (TOE) demonstrated marked right-heart and pulmonary artery dilatation. TREATMENT AND COURSE: Despite thrombolytic treatment (bolus of 50 mg r-TPA; one day later bolus of 1 million IU urokinase followed by 100,000 IU/h) a new thromboembolus was seen by TOE to straddle the pulmonary artery bifurcation. After the urokinase dosage had been raised to 200,000 IU/h TOE on the 6th day no longer showed the embolus and documented a reduction in right-heart dilatation associated with improved haemodynamics. CONCLUSION: TOE is an ideal method for the rapid diagnosis and for monitoring the response to treatment of fulminant pulmonary arterial embolism. As it can also diagnose thromboembolism without significant haemodynamic consequences it is possible to adjust fibrinolytic treatment accordingly.     

Psychoautonomic and neurovascular disorders in patients with autonomic vascular dystonia and the hyperventilation syndrome and methods for their correction

35 patients with vegetocirculatory dystonia and hyperventilation syndrome, but without the signs of organic lesion of nervous system were treated. The complex treatment included the breathing exercises with feedback mechanisms, the correction of psychovegetative and neurovascular disturbances, the massage of neck region and a head, psychotherapy, angioprotective, vegeto- and psychotropic drug therapy. The disappearance of acute vascular attacks and paroxysms of migrainous headache, the normalization of all breathing parameters and the improvement of vegetative status were observed in all patients.     

Frequency of familial inheritance among 488 index patients with idiopathic focal dystonia and clinical variability in a large family

Idiopathic torsion dystonia is characterized by involuntary twisting movements and postures. One molecularly defined form with generalized dystonia has been shown to be autosomal dominantly inherited with reduced penetrance in chromosome 9q34.1, especially in Ashkenazi Jewish families, while other generalized families from Europe and families with other subtypes of dystonia have been excluded from linkage to this locus. Genealogical studies suggest that the much more frequent focal dystonia follows an autosomal dominant inheritance with reduced penetrance as well. For our study, 488 patients with focal dystonia, without a tendency for generalization, were interviewed for their family history. Evidence for hereditary disposition was found in 88 individuals. In a second step, all available family members of 17 of the 488 index patients (chosen for cooperation) were clinically examined. Objective diagnosis of affected relative was established in 13 families, whereas only 4 of the 17 index patients had previously admitted a positive family history. Furthermore, a large three-generation family with focal dystonia linked to chromosome 18p (linkage data described elsewhere) was identified. The familial pattern of all reported families is compatible with autosomal dominant inheritance with reduced penetrance. Assessment only on patients' report leads to underestimation of the frequency of familial idiopathic focal dystonia.     

Precapillary pulmonary hypertension of uncertain etiology

HISTORY AND CLINICAL FINDINGS: A 39-year-old man was hospitalized for investigation of increasing dyspnoea for 3 month. On admission he was found to have bilateral ankle oedema, an enlarged liver and loud systolic murmur over the lower sternum. INVESTIGATIONS: There were signs of right heart strain/hypertrophy on the chest radiogram and echocardiogram. After treatment of right heart failure cardiac catheterization indicated moderate precapillary pulmonary hypertension (PH) with a mean pulmonary artery pressure (PAPm) of 24 mm Hg and pulmonary vascular resistance (PVR) of 470 dyn.s.cm-5 at rest. All known causes having been excluded, the PH was classified as idiopathic. TREATMENT AND COURSE: Evidence of acute pulmonary vascular reactivity was obtained with nitric oxide (NO) inhalation and oral diltiazem, a calcium-channel blocker. The latter, at a dosage of 3 x 120 mg daily, had after 13 days achieved a persisting reduction of PVR at rest and a reduction in PAP rise during exercise. CONCLUSION: After exclusion of other causes, the acute right heart failure was found to be due to primary pulmonary hypertension. The therapeutic efficacity of diltiazem as a vasodilator can be predicted from the response to inhaled NO.     

Plasma brain natriuretic peptide in assessment of acute dyspnoea

Recognition of heart failure (HF) may be difficult in patients presenting with acute dyspnoea, particularly in the presence of chronic airways obstruction. Since increased secretion of the cardiac hormones atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) occurs early in the course of HF, we have assessed the value of measuring these hormones in plasma in the diagnosis of suspected HF in 52 elderly patients presenting with acute dyspnoea, and compared values with left-ventricular ejection fraction (LVEF), a standard measure of left-ventricular function, by radionuclide angiography. Patients were enrolled prospectively. On the basis of clinical findings, conventional tests, and response to specific treatment, 20 of the 52 patients were classified as having primary lung disorder (PLD), 12 as HF alone, and 20 as HF with underlying PLD (HF/PLD). Compared with findings in PLD patients, LVEF was significantly depressed in HF and HF/PLD patients (p < 0.001), whereas both plasma ANP and BNP were significantly increased (p < 0.001). Admission plasma BNP concentration more accurately reflected the final diagnosis of HF (93% sensitivity and 90% specificity when BNP > or = 22 pmol/L) than LVEF or plasma ANP concentration. When all patients were considered together, there were strong negative correlations between LVEF and log BNP (r = -0.7, p < 0.001) and log ANP (r = -0.59, p < 0.001). Our finding that plasma BNP is raised in dyspnoeic patients with HF but not in acutely breathless patients with PLD, suggests that rapid BNP assays may assist in the diagnosis of patients with acute dyspnoea.     

Rapid treatment of acute psychosis

Twenty-four patients with acute functional psychoses were treated with intramuscular haloperidol in a three-hour period. There was almost complete remission of cardinal symptoms (thought disorder, hallucinations, and delusional activity) in this period for 11 patients. Acute dystonia, easily reversed, was the only significant side effect. The authors therefore suggest that outpatient management may be feasible and preferable in the treatment of some acute psychotic episodes.     

Reconstruction after proximal gastrectomy using a stapled, U-shaped jejunal pouch

Any model for the physiology of dystonia must be able to explain how dystonia can be produced in various circumstances. Brain lesions can cause dystonia; responsible sites include the basal ganglia, brainstem, and thalamus, but the most common site is the putamen. Dystonia can be hereditary, and genetic linkage has been found for both generalized and focal dystonia. The only genetic dystonia for which the gene product is known is Segawa disease, a hereditary progressive dystonia with marked diurnal fluctuation. The defect is in guanosine triphosphate cyclohydrolase I, a gene that makes a cofactor for the synthesis of dopamine, which explains why this form of dystonia should be amenable to treatment with levodopa. Another example of dystonia in which a disorder of dopamine pharmacology appears responsible is the dystonia occurring in Parkinson disease, either spontaneously or as a result of treatment. Curiously, the dystonia occurs at both peak and trough dopamine levels.     

Long-term follow-up of levodopa responsiveness in generalized dystonia

OBJECTIVES: To assign an accurate diagnosis to patients with dystonia based on the presence of sustained levodopa responsiveness and to determine whether motor fluctuations occur in patients with dystonia who are withheld from levodopa. PATIENTS AND METHODS: Patients with generalized dystonia who responded to treatment in the 1970s with levodopa/carbidopa were surveyed by phone and then examined during a 3-day levodopa holiday. Functional imaging with fluorodopa positron emission tomography was performed on a subset of patients. RESULTS: In the phone interview, 4 of 7 patients with a diagnosis of dopa-responsive dystonia reported the wearing-off effect a short while (within 4-8 hours) after missing a dose of levodopa. Five patients with dopa-responsive dystonia were examined repetitively during levodopa withdrawal, and 3 developed recurrent symptoms of dystonia as the drug was withheld. In each case, worsening of dystonia did not occur until 29 hours or more after levodopa withdrawal, providing evidence for a response profile similar to the long duration response described in Parkinson disease. No significant changes were seen in the dystonia scores of the 3 patients with idiopathic torsion dystonia who were withheld from levodopa. CONCLUSIONS: We suggest that the subjective feeling of wearing off experienced by our patients with dopa-responsive dystonia may have been for one of the nonmotor effects of levodopa, such as mood elevation. Our data provide objective evidence for the often-repeated assertion that motor fluctuations (analogous to those in levodopa-treated patients with Parkinson disease) do not occur in patients with dopa-responsive dystonia.     

Spironolactone and acute mountain sickness

Thirteen adults trekking in Nepal in 1974 to altitudes between 4,300 m and 5,500 m remained free from acute mountain sickness while taking spironolactone as a prophylactic measure. Two years previously five of these adults trekking at similar altitudes, but without treatment, had suffered from acute mountain sickness. The regime used was spironolactone in a dosage of 25 mg three times a day for two days preceding and during the periods spent at altitudes above 3,000 m.     

Myocardial infarct in the puerperium

Two women of 34 and 31 years suffered an acute myocardial infarction in the puerperium. One of them had many risk factors for atherosclerosis: hypercholesterolaemia, hypertriglyceridaemia, diabetes mellitus, hypertension, obesity, nicotine abuse and a positive family history for cardiovascular disease. She had an occluded right coronary artery and was successfully treated with percutaneous transluminal coronary angioplasty. The other patient had an acute myocardial infarction after her first delivery. She was known with hypercholesterolaemia, obesity and nicotine abuse. During her latest pregnancy she was treated with acetylsalicylic acid. Again she developed an acute myocardial infarction in the puerperium, probably due to coronary dissection. Although the incidence of acute myocardial infarction is low in the peripartal period (less than 1 in 10,000) the diagnosis should be considered when a woman presents with chest pain or dyspnoea.     

Metabolic support of collecting duct transport

This study investigated the impact of deep diaphragmatic breathing (DB) on blood gases, breathing pattern, pulmonary mechanics and dyspnoea in severe hypercapnic chronic obstructive pulmonary disease (COPD) patients recovering from an acute exacerbation. Transcutaneous partial pressure of carbon dioxide (Ptc,CO2) and oxygen (Ptc,O2) and arterial oxygen saturation (Sa,O2), were continuously monitored in 25 COPD patients with chronic hypercapnia, during natural breathing and DB. In eight of these patients, breathing pattern and minute ventilation (V'E) were also assessed by means of a respiratory inductance plethysmography. In five tracheostomized patients, breathing pattern and mechanics were assessed by means of a pneumotachograph/pressure transducer connected to an oesophageal balloon. Subjective rating of dyspnoea was performed by means of a visual analogue scale. In comparison to natural breathing deep DB was associated with a significant increase in Ptc,O2 and a significant decrease in Ptc,CO2, with a significant increase in tidal volume and a significant reduction in respiratory rate resulting in increased V'E. During DB, dyspnoea worsened significantly and inspiratory muscle effort increased, as demonstrated by an increase in oesophageal pressure swings, pressure-time product and work of breathing. We conclude that in severe chronic obstructive pulmonary disease patients with chronic hypercapnia, deep diaphragmatic breathing is associated with improvement of blood gases at the expense of a greater inspiratory muscle loading.     

Pathophysiologies of dystonia and myoclonus--consideration from the standpoint of treatment

Pathophysiologies of disorders with dystonia or myoclonus were studied by evaluating the effects of treatment. Naturally, the main lesion of the dystonia responding to levodopa is in the nigrostriatal dopamine neuron. The target of stereotaxic operations is ventrolateral palladium for postural dystonia and the nucleus ventralis oralis posterior (Vop) thalamus for action dystonia. Torsion dystonia with lesion in the striatum and/or the pallidum causes axial torsion, it may be postural through the descending pathway and action through Vop. Stereotaxic operations on these pathways have shown to be effective. Focal dystonia is a reflection of abnormal co-activation of cortical motor neurons, occurring in a particular voluntary movement. Botulinus toxin injected into the affected muscle should be effective. Of myoclonus with epilepsy, cortical reflex myoclonus or cortical induced reticular myoclonus responds to valproic acid. However, no antiepileptic drugs are effective on those with primary brainstem lesion. Reticular reflex myoclonus due to asphyxia responds to ventralis intermedius thalamotomy. Idiopathic myoclonus associated with dystonia is particular because it responds to ventrolateral thalamotomy. Myoclonus except for idiopathic myoclonus with dystonia is associated with atonic NREM suggesting dysfunction of the dorsal raphe serotonergic neuron or the brainstem nucleus reticularis gigantocellularis, the causative neuron for experimental uremic myoclonus. Treatment for these neurons is necessary.     

Reversible airflow limitation in adults with respiratory infection

The aim of the study was to determine the occurrence of airflow limitation and the frequency of significant reversibility in respiratory infections in adults without known asthma or chronic obstructive pulmonary disease (COPD). We also wanted to study the association between airflow limitation and aetiological agents diagnosed by serological analyses. Spirometry was performed in 574 adult general practice patients with upper or lower respiratory tract infection, and follow-up measurement was obtained in 429 of them. In the latter group, we also obtained paired sera for analysis of anti-bodies against respiratory viruses, chlamydial and mycoplasmal agents. Median forced expiratory volume in one second (FEV1) in all patients included was 90% of predicted; significantly lower in patients with an established diagnosis of asthma or COPD, compared to those without, 77 and 91% predicted, respectively. Among the patients without known asthma or COPD there was a strong association between low FEV1 and the symptoms cough and dyspnoea. Both acute-phase and follow-up FEV1 was measured in 395 of the patients without known asthma or COPD, and a significant increase in median value from 92 to 96% was registered. A reversibility of FEV1 of > 15% was measured in 23% of the 395 patients, uninfluenced by anti-asthma treatment in the great majority. Patients with an established viral, mycoplasmal or chlamydial infection had a significantly lower FEV1 at entry and a greater reversibility, compared to those without such aetiological diagnosis. We conclude that reversible obstruction was particularly common in the patients diagnosed as having acute bronchitis, but that it was found in the patients patients diagnosed as having upper respiratory tract infection.(ABSTRACT TRUNCATED AT 250 WORDS)     

MPTP induces dystonia and parkinsonism. Clues to the pathophysiology of dystonia

The pathophysiology of dystonia is unclear, but several clues implicate striatal dopamine dysfunction. In contrast, the causal relationship between striatal dopamine deficiency and parkinsonism is well defined. We now suggest that parkinsonism or dystonia may occur following striatal dopamine deficiency. Baboons treated with intracarotid 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) developed transient hemidystonia prior to hemiparkinsonism. The day after MPTP treatment, most animals had spontaneous ipsilateral turning. Within a few days, all developed contralateral hemidystonia, with the arm and leg extended and externally rotated. This transient dystonia preceded hemiparkinsonism with flexed posture, bradykinesia, and postural tremor that persisted for up to 1.5 years. Dystonia corresponded temporally with a decreased striatal dopamine content and a transient decrease in D2-like receptor number. The time course of dystonia and parkinsonism is analogous to lower limb dystonia as the first, frequently transient, symptom of Parkinson's disease in humans. The association of striatal dopamine deficiency with dystonia and parkinsonism implies that other factors influence clinical manifestations.     

Diagnosis of pulmonary thromboembolism in a cat using echocardiography and pulmonary scintigraphy

A 10-year-old male cat was presented with sudden onset of respiratory difficulties. Clinical examination revealed an acute dyspnoea with cyanosis associated with a left systolic heart murmur. Standard thoracic radiographs excluded pulmonary oedema and showed very few pulmonary changes given the intensity of the respiratory compromise. Echocardiographic examination revealed hypertrophic cardiomyopathy and a thrombus in the right pulmonary artery. Pulmonary scintigraphy confirmed a pulmonary thromboembolism with hypovascularisation of the left cranial lobe and of the ventral segment of the right lobe. Conservative treatment was instituted using an antibiotic (doxycycline), anticoagulants (heparin, coumadine) and a calcium inhibitor (diltiazem). The cat was given absolute rest. The general condition of the animal improved.