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.

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.

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.

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.

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.

Septic pulmonary and systemic embolism in tricuspid endocarditis.

A 28-year-old woman presenting with fever was referred to our hospital and diagnosed as septic pulmonary embolism secondary to tricuspid valve endocarditis. Although antibiotic therapy was initiated, she further showed multiple complications including Janeway lesions and cerebral infarctions, suggestive of septic systemic embolism. Transoesophageal echocardiography detected a right-to-left shunt through a patent foramen ovale (PFO). The patient was successfully treated with surgical tricuspid valvuloplasty and PFO closure. Paradoxical systemic embolism may occur in patients with septic pulmonary embolism through the PFO.

Schinzel-Giedion syndrome: a further cause of early myoclonic encephalopathy and vacuolating myelinopathy.

Here, we report a male child with Schinzel-Giedion syndrome associated with intramyelinic edema detected on brain magnetic resonance imaging (MRI) and persistent suppression-burst pattern on electroencephalography (EEG) with erratic myoclonus of the extremities and face. Similar to nonketotic hyperglycinemia, Schinzel-Giedion syndrome may be recognized as another causative genetic disease of early myoclonic encephalopathy and vacuolating myelinopathy.

[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.

Clinical features and outcome of patients with IRAK-4 and MyD88 deficiency.

Autosomal recessive interleukin-1 receptor-associated kinase (IRAK)-4 and myeloid differentiation factor (MyD)88 deficiencies impair Toll-like receptor (TLR)- and interleukin-1 receptor-mediated immunity. We documented the clinical features and outcome of 48 patients with IRAK-4 deficiency and 12 patients with MyD88 deficiency, from 37 kindreds in 15 countries.The clinical features of IRAK-4 and MyD88 deficiency were indistinguishable. There were no severe viral, parasitic, and fungal diseases, and the range of bacterial infections was narrow. Noninvasive bacterial infections occurred in 52 patients, with a high incidence of infections of the upper respiratory tract and the skin, mostly caused by Pseudomonas aeruginosa and Staphylococcus aureus, respectively. The leading threat was invasive pneumococcal disease, documented in 41 patients (68%) and causing 72 documented invasive infections (52.2%). P. aeruginosa and Staph. aureus documented invasive infections also occurred (16.7% and 16%, respectively, in 13 and 13 patients, respectively). Systemic signs of inflammation were usually weak or delayed. The first invasive infection occurred before the age of 2 years in 53 (88.3%) and in the neonatal period in 19 (32.7%) patients. Multiple or recurrent invasive infections were observed in most survivors (n = 36/50, 72%).Clinical outcome was poor, with 24 deaths, in 10 cases during the first invasive episode and in 16 cases of invasive pneumococcal disease. However, no death and invasive infectious disease were reported in patients after the age of 8 years and 14 years, respectively. Antibiotic prophylaxis (n = 34), antipneumococcal vaccination (n = 31), and/or IgG infusion (n = 19), when instituted, had a beneficial impact on patients until the teenage years, with no seemingly detectable impact thereafter.IRAK-4 and MyD88 deficiencies predispose patients to recurrent life-threatening bacterial diseases, such as invasive pneumococcal disease in particular, in infancy and early childhood, with weak signs of inflammation. Patients and families should be informed of the risk of developing life-threatening infections; empiric antibacterial treatment and immediate medical consultation are strongly recommended in cases of suspected infection or moderate fever. Prophylactic measures in childhood are beneficial, until spontaneous improvement occurs in adolescence.

Central tegmental tract lesion in a girl with holoprosencephaly presenting with West syndrome.

We described a 16-month-old female patient who developed West syndrome at 3 months of age. MRI revealed a holoprosencephaly with incomplete fusion of the cerebrum, associated with central tegmental tract (CTT) lesions. At 1 year of age, the CTT lesion was still present on T2-weighted MRI. The CTT represents an important projection pathway of the extrapyramidal tract and the CTT lesions have rarely been reported using MRI in patients with neonatal hypoxic-ischemic encephalopathy and several inborn errors of metabolism. Although the exact mechanism remains obscure, we suggest that disturbances in midbrain fibers that connect to the basal ganglia, may have contributed to the etiology of West syndrome in this patient.

[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.

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.

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.

Neonatal-onset brainstem reticular reflex myoclonus following a prenatal brain insult: generalized myoclonic jerk and a brainstem lesion.

Brainstem reticular reflex myoclonus (BRRM) is characterized by sudden, generalized, shock-like movements that can be elicited by sensory stimulation. We present a boy, born after 35 weeks gestation, who was diagnosed with neonatal-onset BRRM. Within 1 hr of birth, the patient showed spasticity and generalized clonic movements of all limbs elicited with tactile stimulation anywhere on the body. Surface electromyography showed co-contraction of agonistic and antagonistic muscles, revealing that his generalized clonic movements were tremulous myoclonus in nature. Brain magnetic resonance imaging (MRI) at 21 hrs after birth disclosed high-intensity lesions in the Rolandic area, thalamus, basal ganglia, and brainstem, including the dorsal pons and medulla, the center of BRRM, in T1-weighted images. Follow-up MRI at 1 month revealed dramatic improvement in the pontine lesion. The patient showed gradual remission of the characteristic movements, which disappeared at 1 year of age, but the patient died unexpectedly at 1 year and 3 months. In conclusion, neonatal BRRM arises as a result of severe brainstem injury, and the associated lesions may only be seen temporarily on MRI taken soon after birth.

Delayed separation of the umbilical cord in two siblings with Interleukin-1 receptor-associated kinase 4 deficiency: rapid screening by flow cytometer.

We describe 2 siblings who had interleukin-1 receptor-associated kinase 4 deficiency with a novel mutation in exon 2. They had delayed separation of the umbilical cord. The flow cytometric analysis of monocytic intracellular tumor necrosis factor-alpha production in response to lipopolysaccharide may be a useful method to screen for the disease.

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.

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.