Combined effect of pulmonary rehabilitation and music therapy in patients with chronic obstructive pulmonary disease.

[Purpose] We aimed to analyze parameters of pulmonary function and physiological, psychological, and physical factors in patients with chronic obstructive pulmonary disease (COPD) receiving pulmonary rehabilitation (PR) and music therapy (MT). [Participants and Methods] This randomized crossover comparative study included in-patients diagnosed with COPD and a ratio of forced expiratory volume measured at the first second and forced vital capacity (FEV1/FVC) of <70% after administration of a bronchodilator. Patients were randomly divided into two groups that received either PR only or MT and PR (n=13 each). The PR program included conditioning, respiratory muscle training, and endurance training, whereas the MT program included vocal, singing, and breathing exercises using a keyboard harmonica. The programs lasted 8 weeks, in which pre- and post-intervention data were compared every 4 weeks. [Results] The FEV1/FVC in the MT group improved after the intervention. Expiratory volume control was obtained better with feedback by sound than with expiration practice. In the MT and PR program, it was easier to adjust the timing and volume of breathing, obtain expiratory volume control, and, thus, improve FEV1/FVC than in conventional practice. [Conclusion] Combining MT with PR improves parameters of pulmonary function in patients with COPD. Music therapy is a novel approach that, in combination with PR, may be used in COPD management.

Outcome of renal proximal tubular dysfunction with Fanconi syndrome caused by sodium valproate.

BACKGROUND: Although Fanconi syndrome is rare in patients with epilepsy treated with sodium valproate (VPA), the prevalence might be higher in children with severe motor and intellectual disabilities (SMID). VPA-induced Fanconi syndrome usually has a favorable outcome, but the long-term outcome of renal tubular dysfunction in SMID patients remains unknown. The aim of this study was therefore to investigate the long-term outcome of renal proximal dysfunction in SMID children with Fanconi syndrome caused by VPA. METHODS: The records of six children with SMID and Fanconi syndrome caused by VPA were retrospectively reviewed to assess long-term proximal renal tubular function after discontinuation of VPA. All six patients had intractable epilepsy and required tube feeding. RESULTS: Proximal tubular dysfunction improved in almost all patients after VPA discontinuation, although abnormal uric acid reabsorption persisted in three patients. Five patients had hypocarnitinemia. After carnitine supplementation, one of these three patients with decreased ability to reabsorb uric acid had a normal serum level and improved fractional excretion of uric acid. CONCLUSIONS: Secondary carnitine deficiency may cause prolonged tubular dysfunction in some SMID patients with VPA-induced Fanconi syndrome. Fanconi syndrome caused by VPA is a usually reversible dysfunction of the proximal tubules, but can be permanent. Although not effective for all patients, carnitine is recommended for patients with VPA-induced Fanconi syndrome, especially children with SMID.

Immediate effects of rhythmic auditory stimulation on gait in stroke patients in relation to the lesion site.

[Purpose] Rhythmic auditory stimulation has been used in gait training for stroke patients. However, few studies have investigated its effects in relation to lesion sites. Therefore, this study examined the immediate effects of rhythmic auditory stimulation on gait in stroke patients with lesions in different regions. [Subjects and Methods] One hundred and five patients were recruited and divided into five groups according to the lesion site: cerebellum, pons and medulla, thalamus, putamen, and corona radiata. During training, participants walked to an auditory, continuous rhythmic beat, which was set to each individual's cadence. [Results] Pre- versus post-test measures revealed significant increases in velocity and stride length in the cerebellum, pons and medulla, and thalamus groups. Although the putamen and corona radiata groups demonstrated increases in velocity and stride length, the increases were not significant. [Conclusion] Rhythmic auditory stimulation was effective in facilitating the prediction of motor timing and gait rhythm in stroke patients with lesions in the cerebellum, pons and medulla, and thalamus, which are associated with impairment of the timing mechanism.

[Anti-convulsant therapy].

Treatment for seizures during acute encephalopathy and encephalitis is not so different from those for seizures due to other etiologies. However, it is sometimes accompanied with intensive care and we also have to pay attention to consciousness disturbance, because it is difficult to determine whether consciousness disturbance is caused by encephalopathy itself, or effect of anticonvulsant therapy, especially in early stage of acute encephalopathy. In Japanese guideline of treatment for influenza encephalopathy, an intravenous administration of diazepam or midazolam as first-line agent, phenobarbital or phenytoin as second-line agent, and midazolam (continuous) or thiopental as third-line agent, were recommended for therapy for status epilepticus.

Lowered Rhythm Tapping Ability in Patients With Constructional Apraxia After Stroke.

Rhythm tapping tasks are often used to explore temporal reproduction abilities. Many studies utilizing rhythm tapping tasks are conducted to evaluate temporal processing abilities with neurological impairments and neurodegenerative disorders. Among sensorimotor and cognitive disorders, rhythm processing abilities in constructional apraxia, a deficit in achieving visuospatial constructional activities, has not been evaluated. This study aimed to examine the rhythm tapping ability of patients with constructional apraxia after a stroke. Twenty-four patients were divided into two groups: with and without constructional apraxia. There were 11 participants in the constructional apraxia group and 13 in the without constructional apraxia group. The synchronization-continuation paradigm was employed in which a person performs a synchronized tapping activity to a metronome beat and continues tapping after the beat has stopped. For statistical analysis, a three-way mixed analysis of variance (2 × 2 × 3) was conducted. The factors were groups (with and without constructional apraxia), tapping tasks (synchronization and continuation), and inter-stimulus intervals (600, 750, and 1000 ms). A significant effect of group factor was found (F[1,132] = 16.62; p < 0.001). Patients in the without constructional apraxia group were able to more accurately reproduce intervals than those in the constructional apraxia group. Moreover, a significant effect of tapping tasks was found (F[1,132] = 8.22; p < 0.01). Intervals were reproduced more accurately for synchronization tasks than continuation tasks. There was no significant inter-stimulus interval effect. Overall, these results suggest that there might be a relation between temporal and spatial reproductions in a wide spectrum of processing levels, from sensory perception to cognitive function.

Effectiveness of lidocaine infusion for status epilepticus in childhood: a retrospective multi-institutional study in Japan.

We evaluated the usefulness of intravenous lidocaine therapy for managing of status epilepticus (SE) during childhood in a retrospective multi-institutional study. Questionnaires were sent to 28 hospitals concerning patients admitted for SE who were managed with lidocaine, assessing patient characteristics, treatment protocols and efficacy. In 279 treated patients, 261 SE occurrences at ages between 1 month and 15 years were analyzed. SE was classified as showing continuous, clustered, or frequently repeated seizures. Considering efficacy and side effects in combination, the usefulness of lidocaine was classified into six categories: extremely useful, useful, slightly useful, not useful, associated with deterioration, or unevaluated. In 148 SE cases (56.7%), lidocaine was rated as useful or extremely useful. Multivariate analysis indicated lidocaine was to be useful in SE with clustered and frequently repeated seizures, and SE attributable to certain acute illnesses, such as convulsions with mild gastroenteritis. Efficacy was poor when SE caused by central nervous system (CNS) infectious disease. Standard doses (approximately 2mg/kg as a bolus, 2mg/kg/h as maintenance) produced better outcomes than lower or higher doses. Poor responders to the initial bolus injection of lidocaine were less likely to respond to subsequent continuous infusion than good initial responders. We recommend lidocaine for use in SE with clustered or frequently repeated seizures, and in SE associated with benign infantile convulsion and convulsions with mild gastroenteritis. Lidocaine should be initiated with a bolus of 2mg/kg. If SE is arrested by the bolus, continuous maintenance infusion should follow; treatment should proceed to different measures when SE shows a poor response to the initial bolus of lidocaine.

[Case of west syndrome associated with transient marked sinus dysfunction during ACTH therapy].

An 11-month-old boy with multiple congenital anomalies developed West syndrome and ACTH therapy was started. Marked bradycardia during sleep was observed after the 16th day of ACTH therapy. Echocardiography revealed both intraventricular septum and left ventricular free wall thickening with preservation of biventricular function. Both the patient's marked sinus dysfunction and his cardiac hypertrophy were suspected to be related to the ACTH therapy. Sinus function gradually improved after ACTH therapy was withdrawn and treatment with oral beta-agonist was started. We believe that the patient's sinus dysfunction and cardiac hypertrophy were caused by ACTH treatment because of the subacute nature of the onset and the absence of other potentially contributory factors such as infection or respiratory failure. Pediatricians should be aware that cardiac dysfunction could be associated with ACTH therapy for West syndrome.

Efficacy of intravenous midazolam for status epilepticus in childhood.

A retrospective multicenter study was conducted, designed to evaluate the efficacy and safety of midazolam for the treatment of status epilepticus. The subjects were 358 inpatients who received intravenous midazolam therapy for status epilepticus. The mean age was 48.6 +/- 46.5 months. The underlying disorder was epilepsy in 195 cases, and acute symptomatic diseases in 163 (encephalitis or encephalopathy in 88 cases). Midazolam was administered as a bolus dose (0.25 +/- 0.21 mg/kg), followed if necessary by continuous infusion (0.26 +/- 0.25 mg/kg/hr). The bolus injection was effective in 162 (56.6%) of the 286 cases. In the end, seizure suppression was obtained in 231 cases (64.5% of the total). The effectiveness of midazolam was lower in patients in whom midazolam was initiated more than 3 hours after seizure onset, and this tendency was particularly marked in the epilepsy group. During the treatment period, 10 patients died, but none of these deaths were associated with midazolam therapy. The incidence and types of adverse events were consistent with previously reported data. The present results indicate that midazolam is highly effective for the management of status epilepticus, if used sufficiently early after seizure onset.

Serial changes on diffusion-weighted magnetic resonance imaging in encephalitis or encephalopathy.

It is recognized that diffusion-weighted magnetic resonance imaging is a sensitive method of detecting cerebral lesions in various neurologic disorders. This report presents two patients with acute encephalitis or encephalopathy who manifested similar serial changes on diffusion-weighted magnetic resonance imaging. Clinically, Patient 1, a 2-year-old male, was diagnosed as having hemiconvulsion-hemiplegia-epilepsy syndrome and Patient 2, a 9-month-old male, acute encephalitis associated with exanthema subitum. Despite the different etiology and the distribution of lesions, diffusion-weighted magnetic resonance imaging of these two patients revealed high-intensity lesions in the subcortical white matter in the acute phase, and then in the cortex, or basal ganglia, or both. In the convalescent phase, high-intensity lesions disappeared and brain atrophy developed. These serial changes were not recognized using other conventional methods. Although the exact mechanism for these serial changes remains unknown, these changes might reflect some pathogenic mechanism in acute encephalopathy or encephalitis.

[Child case of chronic inflammatory demyelinating polyneuropathy showing phagocytic myelinolysis and regenerative changes on electron microscopic analysis of the sural nerve].

We reported a 9-year-old boy with chronic inflammatory demyelinating polyneuropathy (CIDP) showing characteristic electron microscopic study findings on a sural nerve biopsy. He came to our hospital because of muscle weakness progressing slowly for 2 years. He developed distal muscle weakness and areflexia. Cerebrospinal fluid protein was elevated without pleocytosis. Moter conduction velocities were reduced. Partial conduction block and abnormal temporal dispersion were present. The electron microscopic findings on a sural nerve biopsy comprised both active demyelinating lesions, i.e., macrophages were peeling away the myelin lamellae and phagocytosing some myelin debris, and remyelinating lesions with onion bulb formations. Some findings mimic electron microscopic changes in Guillain-Barré syndrome, although tests for the known anti-ganglioside antibodies were negative. So, he was diagnosed as having definite CIDP and prednisolone with gamma-globulin infusion was effective to ameliorate his symptoms.

Invasive Bacterial Infection in Patients with Interleukin-1 Receptor-associated Kinase 4 Deficiency: Case Report.

Interleukin-1 receptor-associated kinase 4 (IRAK4) deficiency (OMIM #607676) is a rare primary immunodeficiency of innate immune defect. We identified 10 patients from 6 families with IRAK4 deficiency in Japan, and analyzed the clinical characteristics of this disease. Nine patients had homozygous c.123_124insA mutation, and 1 patient had c.123_124insA and another nonsense mutation (547C>T). Umbilical cord separation occurred on the 14th day after birth or thereafter. Two patients had no severe infections owing to the prophylactic antibiotic treatment. Severe invasive bacterial infections occurred before the age of 3 in the other 8 patients. Among them, 7 patients had pneumococcal meningitis. Five patients died of invasive bacterial infection during infancy, although intravenous antibiotic treatment was started within 24 hours after onset in 4 patients among them. Analysis of cerebrospinal fluid of the patients who had fatal meningitis revealed very low glucose levels with only mild pleocytosis. The clinical courses of invasive bacterial infections were often rapidly progressive despite the early, appropriate antibiotic treatment in IRAK4 deficiency patients. The early diagnosis and appropriate prophylaxis of invasive bacterial infections are necessary for the patients.

Acute respiratory distress syndrome in children with severe motor and intellectual disabilities.

We report 13 severely disabled children with acute respiratory distress syndrome, who were treated at the Department of Pediatrics, Niigata City General Hospital between 1995 and 2002. The children ranged in age from 1 year to 16 years. All were non-ambulant. Chronic aspiration and gastro-esophageal reflux were recognized in 12 patients. Patients had the rapid onset of dyspnea refractory to oxygen therapy. Diffuse bilateral lung infiltrates were present on chest X-ray. Predisposing events included sepsis (3 patients), pneumomia (7 patients), pancreatitis (1 patient) and two children with other infections. All required mechanical ventilation for periods of 3-26 days and received oxygen for 5-64 days. Steroid therapy and surfactant therapy were given to eight and three patients, respectively. Only one patient developed an air leak complication. Despite intensive care, three children died, one underwent tracheostomy and nine recovered completely. Acute respiratory distress syndrome is a commonly recognized cause of acute respiratory failure following a variety of insults. It is characterized by the acute onset of dyspnea refractory to oxygen therapy, and diffuse lung infiltrates. Children with severe motor and intellectual disabilities had various complications. In this study, chronic aspiration and gastro-esophageal reflux are considered to be one of predisposing factors triggering acute respiratory distress syndrome in children with severe motor and intellectual disabilities. Although acute respiratory distress syndrome was considered to be a not infrequent occurrence, its mortality rate might be low despite the severity of the disease in children with severe motor and intellectual disabilities. Acute respiratory distress syndrome can be a complication seen in severely disabled children.

Fanconi syndrome caused by sodium valproate: report of three severely disabled children.

We report three severely disabled children with epilepsy, a 4-year-old boy, 8-year-old girl and 14-year-old girl, who were treated with sodium valproate from the age of 2 months, 3 months and 7 years, respectively, and who developed Fanconi syndrome. All three patients were bed-ridden and fed by means of a nasogastric or gastrostomy tube. Since Fanconi syndrome was considered to be caused by sodium valproate, it was stopped. After the discontinuation of sodium valproate, renal involvement improved in all patients in 2-12 months. Severely handicapped children may be at risk for sodium valproate-induced renal involvement. Although among the adverse effects of sodium valproate, renal involvement is uncommon, Fanconi syndrome due to valproate therapy has rarely been reported. We have to pay attention to Fanconi syndrome in epileptic children treated with sodium valproate, especially in severely disabled children.

Benign "setting sun" phenomenon in full-term infants.

I report two normally developed infants showing benign" setting sun" phenomenon. A 2(2-12)-year-old boy and a 7-year-old boy, who were born without any complications at full term, developed brief episodes of downward gazing during sucking and crying after birth However, there were no other clinical or laboratory findings, and they developed normally. The phenomenon was not visible until 6 months and 7 months, respectively. The "setting sun" phenomenon usually indicates underlying severe brain damage and can also be seen, although rarely, in healthy full-term infants until 1 to 5 months. However, the benign "setting sun" phenomenon might exist until 6 or 7 months of age in normal infants.

Periodic lateralized epileptiform discharges in children.

Thirteen children in whom electroencephalography revealed periodic lateralized epileptiform discharges in the acute phase of cerebral involvement were included in this study. Four were diagnosed as having influenza-associated encephalopathy, two nonherpetic limbic encephalitis, two theophylline-associated seizures, one Mycoplasma pneumoniae encephalitis, one acute encephalopathy, and one bacterial meningitis. All patients developed seizures; six developed hemiconvulsions. As to prognosis, two died, six had some neurologic sequelae, and five had no neurologic sequelae. Although periodic lateralized epileptiform discharges are not disease specific, the importance of these disorders had not been focused on as a cause of periodic lateralized epileptiform discharges.

Vitamin K deficiency in severely disabled children.

Vitamin K status was examined in 21 severely disabled children in our hospital from September 2001 to August 2002, and 9 children were found to have a vitamin K deficiency. The 21 patients were divided into two groups: group A, 9 patients with vitamin K deficiency, and group B, 12 patients without vitamin K deficiency. The laboratory data and background factors in the two groups were compared statistically. In group A, all patients received enteral nutrition and anticonvulsants. The protein induced by vitamin K absence-II values were elevated in eight patients. Seven exhibited a bleeding tendency. Six developed vitamin K deficiency in association with infection and four were treated with antibiotics. All showed a good response to the administration of vitamin K. The patients in group A had factors such as use of antibiotics, infection, and elemental nutrition at significantly higher rates than those in group B. Data indicating nutrition factors such as body weight, caloric intake, total protein level, and hemoglobin level were not significantly different between the two groups. Severely disabled children suffer from deficiencies of various nutritional elements. However, vitamin K deficiency in severely disabled children has not been fully investigated. Infection, use of antibiotics, and elemental nutrition are risk factors for vitamin K deficiency in severely disabled children. In severely disabled children, there might be marginal vitamin K intake via enteral nutrition, so more vitamin K supplementation is necessary, especially with infection and use of antibiotics.

Normally developed infant with a suppression burst pattern on electroencephalography in the neonatal period.

The background activity on neonatal electroencephalography (EEG) is a good prognostic indicator. An EEG suppression burst pattern usually indicates severe brain dysfunction and has been considered to be associated with a serious neurodevelopmental outcome. We report here a 2-year-old girl who developed generalized convulsions without any perinatal brain insult at 3 days of age. At that time, her EEG constantly showed a suppression burst pattern, and her prognosis was considered to be poor. However, her seizures were well controlled with the oral administration of carbamazepine, and the suppression burst pattern on EEG disappeared at 27 days of age. Unexpectedly, she developed normally for the following 2 years. Although children with normal development, despite the appearance of suppression burst, are extremely rare, and the reason why this patient showed a favorable outcome remains unknown, the clinical course of this patient proved that an EEG suppression burst pattern is not always associated with a poor prognosis.

Carbamazepine-induced abnormal pitch perception.

A 7-year-old boy began to complain that his pitch perception was decreased just after oral medication with carbamazepine was initiated for the treatment of epilepsy. When he played the piano, he felt as if he had played a musical note of almost a half pitch lower than he had. His pitch perception recovered soon after the cessation of carbamazepine. A 14-year-old girl noted a lowered pitch of music sounds while she played the piano just after the administration of carbamazepine for the treatment of epilepsy. Carbamazepine was withdrawn and the auditory symptoms disappeared. Both patients were musically trained. Reversible pitch perception abnormalities are a rare adverse effect of carbamazepine, however, the clinical features of the reported cases were similar; they were musically trained, young, female and Japanese. Although the mechanism remains unclear, we have to pay attention to this subtle adverse effect when we treat epileptic patients with carbamazepine.

Hypoparathyroidism and facial dysmorphism as main symptoms of 22q.11 deletion syndrome.

A 12-year-old Japanese boy with mental retardation and facial dysmorphism developed frequent convulsions, and hypocalcemia due to hypoparathyroidism was recognized. Chromosomal analysis involving the fluorescence in situ hybridization method revealed a microdeletion of 22q11.2. However, other laboratory examinations revealed no cardiac anomaly, thymic hypoplasia, or cleft palate. It is well known that typical cases of 22q11 deletion syndrome have a cardiac anomaly, thymic hypoplasia and a cleft palate. However, the phenotype of 22q11 deletion syndrome is diverse, and hypoparathyroidism and facial dysmorphism have been reported in nine cases, including this case, associated with 22q11 deletion. This combination of clinical manifestations could be given another term, such as hypoparathyroidism-facial syndrome. Some hypoparathyroidism patients due to 22q11.2 deletion may be misdiagnosed as having idiopathic hypoparathyroidism, and a child diagnosed as having hypoparathyroidism should be examined for chromosomal 22q.11.2. deletion.