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.

Deep brain stimulation for dystonia-choreoathetosis in cerebral palsy: Pallidal versus thalamic stimulation.

INTRODUCTION: Dystonia-choreoathetosis is common in patients with cerebral palsy, and medical treatment is mostly unsatisfactory. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) has shown some effect, but there is still a need to optimize treatment strategies. We aimed to assess whether the thalamic ventral intermediate nucleus (Vim) might be an alternative DBS target in dystonia-choreoathetosis. METHODS: Three patients with cerebral palsy and dystonia-choreoathetosis underwent implantation of DBS electrodes concurrently in the GPi and Vim. Final selection of stimulation site and switches during follow-up with corresponding clinical outcomes were assessed. RESULTS: One patient with initial GPi stimulation was switched to Vim, but likewise did not improve significantly (BFM: pre-OP 142, GPi 140, Vim 134) and stimulation was discontinued. In one patient Vim was chosen as initial target for chronic DBS. Since clinical benefit was not yet satisfying, stimulation was switched to GPi resulting in further mild clinical improvement (BFM: pre-OP 99.5, Vim 82.5, GPi 82). In one patient GPi was selected and kept on follow-up due to some therapeutic effect (BFM: pre-OP 135, GPi DBS 121). CONCLUSIONS: The GPi still represents the most convenient DBS target in patients with dystonia-choreoathetosis. Vim DBS did not show a relevant long-term advantage in everyday life in our patients. Further alternative DBS targets need to be considered in acquired dystonia.

Escalas de compromiso funcional y de movimientos involuntarios en extremidades superiores en niños con trastornos de movimiento de tipo extrapiramidal / Scales evaluating functional compromise and involuntary upper extremity movements in children with extra pyramidal disorders

Introducción. Los niños con parálisis cerebral de tipo extrapiramidal requieren de una evaluación funcional global que mida cambios antes, durante y después de tratamientos. Objetivo. Validar dos escalas de evaluación: compromiso funcional global y tipo de movimiento involuntario predominante en extremidades superiores. Pacientes y método. 63 pacientes seleccionados aleatoriamente de Teleton-Santiago-Chile-2006, diagnóstico parálisis cerebral, alteración de movimiento de tipo extrapiramidal, de 4–18 años, que cumplieron requisitos de inclusión; se aplicó escala de compromiso funcional (con dimensiones: postura sedente, actividades de la vida diaria y funcionalidad manual) y escala de movimientos Involuntarios (atetosis, coreatetosis y distonía). Resultados. La escala de compromiso funcional muestra alta consistencia interna (α Cronbach 0,94), valor kappa de variabilidad entre observadores de 0,78; validez de constructo constituido por 2 componentes principales que explicaron 75,7% de la funcionalidad. La escala clasificó a los niños en 46% como grave o severo, 25,4% como moderado, 20,6% como leve y sólo al 7,9% como clínicamente normal. La escala de movimientos involuntarios registró confiabilidad con valor kappa de 0,85 y consistencia interna de 0,97; clasificó como distónicos al 38,1% de los niños, coreatetósicos el 33,3% y 28,9% como atetósicos. Conclusión. Las escalas demostraron ser confiables y válidas por lo tanto, pueden ser utilizadas como ayuda en la planificación y evolución terapéutica(AU)

Introduction. Children with extrapyramidal cerebral palsy require a comprehensive functional assessment that records their functions before, and measures the changes during and after the treatments. Objective. Validate two assessment scales: global functionality and type of predominant unintentional movement in upper extremities. Patients and method. 63 patients were randomly selected from Teleton-Santiago-Chile-2006, diagnosed with cerebral palsy, extrapyramidal type alteration movement, 4 to 18 years, which met the inclusion requirements: they were evaluated with the functional compromise scale (with dimensions: sitting posture, daily living activities, and manual functionality) and with the involuntary movements scale (athetosis, choreathetosis and dystonia). Results. The scale of functional assessment shows high internal consistency (α Cronbach 0.94), a kappa value of variability among observers of 0.78, and construct validity, which consists of two main components that explained 75.7% of the functionality. The scale ranked children as: 46% as serious or severe, 25.4% as moderate, 20.6% as mild, and only 7.9% as normal. The scale of involuntary movements showed high reliability with kappa value of 0.85 and internal consistency of 0.97, and ranked 38.1% of the children as dystonic, 33.3% as choreathetosics, and 28.9% as athetosics. Conclusion. The scales proved to be reliable and valid therefore can be used as an aid in planning and therapeutic evaluation(AU)

Bilateral pallidal deep brain stimulation for the treatment of patients with dystonia-choreoathetosis cerebral palsy: a prospective pilot study.

BACKGROUND: Cerebral palsy (CP) with dystonia-choreoathetosis is a common cause of disability in children and in adults, and responds poorly to medical treatment. Bilateral pallidal deep brain stimulation (BP-DBS) of the globus pallidus internus (GPi) is an effective treatment for primary dystonia, but the effect of this reversible surgical procedure on dystonia-choreoathetosis CP, which is a subtype of secondary dystonia, is unknown. Our aim was to test the effectiveness of BP-DBS in adults with dystonia-choreoathetosis CP. METHODS: We did a multicentre prospective pilot study of BP-DBS in 13 adults with dystonia-choreoathetosis CP who had no cognitive impairment, little spasticity, and only slight abnormalities of the basal ganglia on MRI. The primary endpoint was change in the severity of dystonia-choreoathetosis after 1 year of neurostimulation, as assessed with the Burke-Fahn-Marsden dystonia rating scale. The accuracy of surgical targeting to the GPi was assessed masked to the results of neurostimulation. Analysis was by intention to treat. FINDINGS: The mean Burke-Fahn-Marsden dystonia rating scale movement score improved from 44.2 (SD 21.1) before surgery to 34.7 (21.9) at 1 year post-operatively (p=0.009; mean improvement 24.4 [21.1]%, 95% CI 11.6-37.1). Functional disability, pain, and mental health-related quality of life were significantly improved. There was no worsening of cognition or mood. Adverse events were related to stimulation (arrest of the stimulator in one patient, and an adjustment to the current intensity in four patients). The optimum therapeutic target was the posterolateroventral region of the GPi. Little improvement was seen when the neurostimulation diffused to adjacent structures (mainly to the globus pallidus externus [GPe]). INTERPRETATION: Bilateral pallidal neurostimulation could be an effective treatment option for patients with dystonia-choreoathetosis CP. However, given the heterogeneity of motor outcomes and the small sample size, results should be interpreted with caution. The optimum placement of the leads seemed to be a crucial, but not exclusive, factor that could affect a good outcome. FUNDING: National PHRC; Cerebral Palsy Foundation: Fondation Motrice/APETREIMC; French INSERM Dystonia National Network; Medtronic.

Hyperkinetic movement disorder in a child treated by globus pallidus stimulation.

We report herein the case of a 9-year-old girl with life-threatening hyperkinetic involuntary movement of unknown etiology. Medical treatment was ineffective for her stereotypy and choreoathetotic/ballistic movements, but bilateral stimulation of the globus pallidus immediately alleviated these symptoms. Pallidal deep-brain stimulation may be considered the therapy of choice for children with intractable hyperkinetic movement disorders.

Bilateral stimulation of the globus pallidus internus to treat choreathetosis in Huntington's disease: technical case report.

OBJECTIVE AND IMPORTANCE: Huntington's disease (HD) produces debilitating motor abnormalities that are poorly responsive to medical therapy. Deep brain stimulation (DBS) may offer a treatment option for afflicted patients, but its role in the management of HD remains unclear. In the present case, DBS leads were implanted bilaterally into the posteroventral globus pallidus internus (GPi) to control disabling and medically intractable choreathetosis in a severely affected HD patient. The surgical procedure, intraoperative electrophysiological findings, and 12-month postoperative course, with patient video, are presented. CLINICAL PRESENTATION: This 41-year-old man with genetically confirmed HD developed motor symptoms at age 28. He had completed multiple medical trials without alleviation of his progressive and debilitating choreathetosis. Extensive clinical assessment, including neuropsychological testing, was performed to determine surgical candidacy. INTERVENTION: DBS leads were bilaterally implanted, under stereotactic guidance, into the posteroventral GPi. Disease progression and symptom control were assessed at regular postoperative intervals. Bilateral pallidal stimulation produced a dramatic reduction in choreathetoid movements and improvement in overall motor functioning. The patient also exhibited normalization of body weight, mood, and energy level, as well as improved performance of activities of daily living. These effects were sustained at 1 year after surgery. CONCLUSION: The clinical benefits of DBS observed in this HD patient were comparable to those reported in other hyperkinetic disorders and demonstrate that pallidal stimulation can provide long-term alleviation of HD-associated choreathetosis.

[Reversible choreoathetosis associated with lithium intoxication].

Several reports have been published in the literature of choreoathetosis associated with lithium intoxication, but little is known about choreoathetosis without concurrent antipsychotic treatment. We report a 65-year-old woman with lithium intoxication whose choreoathetosis completely recovered without sequela following decrease of her serum lithium level. She had been treated elsewhere for bipolar II disorder and also for hypertension, chronic hepatitis type C and diabetes mellitus. As she became hypomanic, lithium carbonate at 600 mg/day was commenced, which was increased to 1200 mg/day due to unfavorable therapeutic response. She began to manifest disorientation and abnormal involuntary movement and was therefore referred to our Department of Psychiatry. Her clinical symptoms at admission included consciousness disturbance with marked bilateral symmetrical slow-wave activity in her EEG and choreoathetosis was observed in her face and upper and lower extremities. Cerebellar symptoms were minimal with only mild ataxic gait and finger-to-nose test did not show dysmetria or intention tremor. Her serum lithium level was 3.52 mEq/L, which was clearly in the toxic range. She demonstrated no metabolic abnormalities including hyperglycemia, and was diagnosed with lithium intoxication and treated with water loading and mannitol for forced diuresis. On the 14th day after admission her consciousness disturbance and choreoathetosis resolved, but EEG abnormalities still persisted. On the 23rd day after admission, she was discharged with clinical remission and normal EEG background activity. Although she developed mild renal dysfunction, hemodialysis was not indicated. Hypersensitivity of dopamine receptor in the nigrostriatal pathways may contribute to choreoathetosis in association with the patient's vulnerability. Choreoathetosis can be a sign of lithium intoxication and prompt treatment is required following careful differential diagnosis.

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.

Vacuolating leukoencephalopathy with subcortical cysts with late onset athetotic movements.

We reported a 10-year-old male with vacuolating leukoencephalopathy with subcortical cysts, who presented athetotic movements in the late stage. Magnetic resonance imaging demonstrated diffuse cerebellar white matter lesions, in addition to typical cerebral white matter abnormalities and characteristic subcortical cysts in the anterotemporal and parietal areas. Fluid-attenuated inversion recovery images are highly sensitive for the detection of subcortical cysts, which is essential for a diagnosis. This is most likely to be a severe form of vacuolating leukoencephalopathy with subcortical cysts, presenting with athetotic movements in the late stage.

Lindane toxicity in a 24-year-old woman.

A case of lindane toxicity in a 24-year-old woman who used lindane shampoo for treatment of an alleged case of lice infestation is described. The patient experienced uncontrolled motor activity that began approximately 2 hours after treatment and resolved approximately 48 hours later. A review of the literature revealed that most cases of acute lindane toxicity resulting from topical application have occurred in the pediatric and geriatric populations and are manifested by grand mal seizures. No case of acute lindane toxicity resulting from topical use was found in the emergency medicine literature. This case illustrates the toxic, neurologic effects of lindane in a young adult.

[The comparison of motor developmental processes between spastic diplegic children and athetotic children who have been treated since infancy].

We studied the correlation between motor developmental processes and prognosis of locomotion at the age of 4 years, among 15 spastic diplegic children (S) and 21 athetotic children (A), who started treatment under 1 year of age. The children of each type were divided into two groups according to the ability of locomotion at the age of 4 years; S- I: 6 walkers, S- II: 9 crawler, A- I: 11 walkers and A- II: 10 crawler. We compared the average corrected ages when the subjects attained the abilities to roll over, creep, sit with hands, crawl, sit up, cruise with support, stand up, and walk alone, and made a statistical analysis by t test among 4 groups. Also we compared the cumulative frequency percentages for the ages about the locomotion mentioned above. The S- I group attained all of the abilities of locomotion significantly earlier than the S- II group. The A- I group could crawl and sit up significantly earlier than the S- II group. The A- I group could crawl and sit up significantly earlier than the A- II group. The S- I group began to creep and sit with hands significantly earlier than the A- I group. We found no significant differences between the S- II group and the A- II group in motor developmental processes. These studies revealed that it would be possible to expect the prognosis of ambulation at the age of 4 years according to the early motor developmental processes among the spastic diplegic children.(ABSTRACT TRUNCATED AT 250 WORDS)