Hypoxaemia and interstitial lung disease in an infant with hypothyroidism and hypotonia.

A 7-month-old-term male infant presented with cough, tachypnoea, hypoxaemia and post-tussive emesis. Clinical history was significant for respiratory failure and pulmonary hypertension in the neonatal period requiring assisted ventilation, congenital hypothyroidism, mild hypotonia, recurrent respiratory infections, hypoxaemia requiring supplemental oxygen and nasogastric tube feeds. Physical examination showed tachypnoea, coarse bilateral breath sounds and mild hypotonia. Chest radiograph revealed multifocal pulmonary opacities with coarse interstitial markings and right upper lobe atelectasis. Following antibiotic therapy for suspected aspiration pneumonia, chest CT scan was performed and showed multiple areas of pulmonary consolidation and scattered areas of bilateral ground-glass opacities. Genetic studies showed a large deletion of chromosome 14q13.1-14q21.1, encompassing the NK2 homeobox 1 (NKX2-1) gene consistent with a diagnosis of brain-thyroid-lung (BTL) syndrome. Our case highlights the importance of genetic studies to diagnose BTL syndrome in infants with hypothyroidism, hypotonia and lung disease.

Combined mutations of NKX2-1 and surfactant protein C genes for refractory low oxyhemoglobin saturation and interstitial pneumonia: A case report.

RATIONALE: Mutations of the NKX2-1 gene are associated with brain-lung-thyroid syndrome, which is characterized by benign hereditary chorea, hypothyroidism, and pulmonary disease with variable presentation. Surfactant protein C (SFTPC) gene mutations result in chronic interstitial lung disease in adults or severe neonatal respiratory distress syndrome. PATIENT CONCERNS: Recurrent hypoxemia was observed shortly after birth in a baby at a gestational age of 40 weeks and birth weight of 3150 g. The need for respiratory support gradually increased. He had hypothyroidism and experienced feeding difficulties and irritability. DIAGNOSIS: Genetic examination of the peripheral blood revealed combined mutations of the NKX2-1 and SFTPC genes. INTERVENTIONS: The patient was administered respiratory support, antibiotics, low-dose dexamethasone, supplementary thyroxine, venous nutrition, and other supportive measures. OUTCOMES: The patient's guardian stopped treatment 3 months after commencement of treatment, due to the seriousness of his condition and the patient died. LESSONS: Combined mutations of NKX2-1 and SFTPC genes are very rare. Thus, idiopathic interstitial pneumonia with hypothyroidism and neurological disorders require special attention.

Chronic stimulation of the globus pallidus internus for treatment of non-dYT1 generalized dystonia and choreoathetosis: 2-year follow up.

OBJECT: The authors studied the long-term efficacy of deep brain stimulation (DBS) of the posteroventral lateral globus pallidus internus up to 2 years postoperatively in patients with primary non-DYT1 generalized dystonia or choreoathetosis. The results are briefly compared with those reported for DBS in DYT1 dystonia (Oppenheim dystonia), which is caused by the DYT1 gene. METHODS: Enrollment in this prospective expanded pilot study was limited to adult patients with severely disabling, medically refractory non-DYT1 generalized dystonia or choreoathetosis. Six consecutive patients underwent follow-up examinations at defined intervals of 3 months, 1 year, and 2 years postsurgery. There were five women and one man, and their mean age at surgery was 45.5 years. Formal assessments included both the Burke-Fahn-Marsden dystonia scale and the recently developed Unified Dystonia Rating Scale. Two patients had primary generalized non-DYT1 dystonia, and four suffered from choreoathetosis secondary to infantile cerebral palsy. Bilateral quadripolar DBS electrodes were implanted in all instances, except in one patient with markedly asymmetrical symptoms. There were no adverse events related to surgery. The Burke-Fahn-Marsden scores in the two patients with generalized dystonia improved by 78 and 71% at 3 months, by 82 and 69% at 1 year, and by 78 and 70% at 2 years postoperatively. This was paralleled by marked amelioration of disability scores. The mean improvement in Burke-Fahn-Marsden scores in patients with choreoathetosis was 12% at 3 months, 29% at 1 year, and 23% at 2 years postoperatively, which was not significant. Two of these patients thought that they had achieved marked improvement at 2 years postoperatively, although results of objective evaluations were less impressive. In these two patients there was a minor but stable improvement in disability scores. All patients had an improvement in pain scores at the 2-year follow-up review. Medication was tapered off in both patients with generalized dystonia and reduced in two of the patients with choreoathetosis. All stimulation-induced side effects were reversible on adjustment of the DBS settings. Energy consumption of the batteries was considerably higher than in patients with Parkinson disease. CONCLUSIONS: Chronic pallidal DBS is a safe and effective procedure in generalized non-DYT1 dystonia, and it may become the procedure of choice in patients with medically refractory dystonia. Postoperative improvement of choreoathetosis is more modest and varied, and subjective ratings of outcome may exceed objective evaluations.

Cerebellar stimulation for cerebral palsy spasticity, function, and seizures.

Chronic cerebellar stimulation (CCS) applied to the superio-medial cortex reduces generalized cerebral spasticity, athetoid movements, and seizures. Eighteen clinics have reported on 600 cerebral palsy (CP) patients who comprise 90% of those treated with CCS. CP patients have varying degrees of limited abilities interfered with by spasticity (primitive reflexes, increased muscle tone, co-contractions, and spasms) and by athetoid movements in two-thirds of the patients. With CCS, spasticity reduction occurred in 85% (marked 25%, moderate 34%, mild 27%) and resulted in improvements in patient drooling, speech, respiration, posture, motor performance, gait, joint range of motion, and mood states. Radiofrequency (RF)-linked stimulators were used initially with serious equipment and calibration problems; 68% of 422 patients improved. When totally implantable controlled-currrent stimulators were used, 86% of 178 patients improved. Our double-blind study of 20 CP patients using this implantable stimulator showed 12 (60%) improved in motor performance, joint range of motion, and profile of mood states when the stimulator was ON. When abilities are graded (1: poor to 9: best), the seven patients with the higher functioning grades (5-8) all improved (99% confidence level). Intractable seizures occurred in 27 (8%) of our CP patients. At a 17-year follow-up, 19 patients contacted were using or had used CCS with 10 (53%) seizure-free and 6 (32%) with reduced seizures. CCS should be given by a totally implanted controlled-current stimulator (1-4 microCoulombs/sq. cm. /phase, 150-200 Hz) applied intermittently to the superio-medial cerebellar cortex for safe, effective, and continuous results.

Head-position training through biofeedback: prosthetic or cure?

This report investigates the effectiveness of biofeedback in the treatment of poor head-positioning in patients with cerebral palsy. Four patients were given feedback of head-position trainer: two were given 20 sessions, the other two were given 10 sessions followed by 10 sessions of social reinforcement. It was found that biofeedback produced significant changes in head control during therapy but that these did not transfer well to other situations, nor did it result in long-term positive improvement. The use of social reinforcement produced excellent and long-term gains. These results are discussed in terms of stimulus properties and reinforcement conditions. General implications of this study in relation to the generalisation and maintenance of behaviour change are also discussed.

Chronic paleocerebellar stimulation in dystonia and athetosis. Report of two cases.

Two patients suffering from dystonia and athetosis have been treated by means of chronic electrical stimulation of the paleocerebellum and were followed for over two and a half years. One of the patients showed signs of slight improvement, while no improvement at all was observed in the other patient. Some observations and problems are discussed.

Effect of sensory integrative therapy on the coordination of children with choreoathetoid movements.

Learning-disabled children with deficits in sensory integration as well as choreoathetosis and who received sensory integrative therapy gained more on an eye-hand coordination test than did control children. Using a one-tailed test, levels of significance difference between the mean gain scores of the experimental and control groups were .058 for the more accurate hand and .061 for the less accurate hand. It is not possible to determine whether the therapeutic effect was on the motor or on the sensory integrative aspect of coordination or on both.

Observations on physiological and psychological functions of the ventral oral internal nucleus of the human thalamus.

Eight patients underwent VOI thalamotomy for spasmodic torticollis or choreoathetosis. The clinical results were disappointing: at follow-up examination 8 months postoperatively, on average, none of the seven patients with torticollis regarded the effect as good. In two there was some long-lasting improvement, but in five the results was nil. One patient with choreoathetosis did not benefit from surgery. Side-effects were frequent but not serious; they included excessive sleepiness, drowsiness, weight increase, deterioration of memory and loss of general activity. Electrical stimulation of the VOI nucleus caused subjective sensations in the neck and shoulder muscles without movements of the head, and autonomic or emotional reactions. An evoked scalp response was recorded in contralateral frontal area 8. As shown by psychological tests, in visuospatial performances there is a preoperative defect, which seems to be specific to spasmodic torticollis. After left VOI thalamotomy both receptive and expressive verbal efficiency were impaired. Visual perception and memory were almost unaffected by VOI thalamotomy.

Chronic cerebellar stimulation in cerebral palsy.

Data are presented for the first 50 patients with cerebral palsy who underwent chronic cerebellar stimulation for symptom alleviation. We observed significant shorter and longer term improvement in spasticity as well as athetosis, speech, and functional status. Continuing increments in improvement were noted as a function of time on stimulation. In many instances, psychometric test scores and behavior also were improved. There was one death in this series. There were no neurologic complications due to cerebellar stimulation. The results of this study warrant the judicious use of cerebellar stimulation for symptomatic and functional relief in cerebral palsy.

Frontal EMG-biofeedback training of athetoid cerebral palsy patients: a report of six cases.

Six athetoid cerebral palsy patients participated in the following: speech and motor prebiofeedback training evaluation; frontal EMG biofeedback training, 6 wk; speech and motor postbiofeedback training evaluation. Frontal pretraining levels for the subjects averaged 28.9 muV p-p. Subjects' feedback consisted of an auditory signal (clicks) varying proportionately with frontal EMG activity. A visual meter display of the integrated EMG was also provided. Self-regulation of frontal EMG was evident for all subjects within session 1. Throughout all sessions, EMG levels of 2-4 mu V were often attained. Trend analysis of EMG acquisition curves showed significant reduction in frontal tension across sessions for all but one subject. Frontal posttraining levels averaged 13.0 muV p-p. Parents or subjects, or both, reported subtle improvements in various speech and motor functions, a finding confirmed by objective postbiofeedback training evaluation. Only the 2 most severely impaired subjects, JA and DS, failed to improve significantly on the speech measures. All subjects improved significantly on those measures that tapped fine and gross motor skills. Collectively, these results indicate that EMG biofeedback training shows promise as an additional treatment modality in the habilitation of cerebral palsy patients.