Successful use of non-invasive positive pressure ventilation in a patient with the severe form of X-linked myotubular myopathy.

The severity of X-linked myotubular myopathy (XLMTM) ranges from mild to severe, depending on the level of ventilatory support required. Patients with the severe form of XLMTM usually die within the first year of life due to respiratory failure. Most survivors need tracheostomies, and there has only been one report about the use of non-invasive positive pressure ventilation (NPPV) in patients with the severe form of XLMTM because of the severity of the associated respiratory failure. We successfully applied NPPV with high-span positive inspiratory pressure (PIP) in a patient with the severe form of XLMTM, who also had secondary pectus excavatum. About a year after the initiation of NPPV with high-span PIP, the patient's pectus excavatum had improved. As the patient's pectus excavatum improved, his respiratory disturbance was ameliorated, and the frequency of respiratory infections gradually decreased. NPPV might be the first-choice respiratory management strategy for patients with XLMTM.

Left ventricular noncompaction cardiomyopathy in a patient with trisomy 13: A report and review of the literature.

Left ventricular noncompaction cardiomyopathy (LVNC) is characterized by prominent trabecular meshwork, and it is thought to result from arrest of the normal compaction process during embryogenesis. Patients with LVNC may be asymptomatic or have symptoms ranging from heart failure to stroke, life-threatening arrhythmias, or sudden death. The frequency of LVNC in children has increased with longer clinical courses. About 80% of patients with trisomy 13 have a congenital cardiac abnormality, but a clinical description of LVNC with trisomy 13 is lacking because of its poor prognosis and lack of awareness about LVNC. We described a patient with trisomy 13 who was diagnosed with LVNC-dilated phenotype and died suddenly, as well as two additional patients with LVNC. All three patients had chronic heart failure without congenital heart disease and were treated with diuretics. To manage trisomy 13 with or without congenital heart disease, cardiac disease such as LVNC may present at any ages, and therefore cardiac evaluation should be considered as a part of their appropriate management.

[Enteral nutrition ameliorated superior mesenteric artery syndrome in a patient with Duchenne muscular dystrophy].

The abdominal complications of Duchenne muscular dystrophy (DMD) include acute gastric dilatation, superior mesenteric artery (SMA) syndrome, ileus and constipation. We report herein a patient with DMD in whom SMA syndrome was successfully treated with enteral tube nutrition. The patient was a 16-year-old boy diagnosed with DMD at 2 years. Steroid therapy was started at 5 years, and he was unable to walk and was wheelchair-bound at 11 years. Lordoscoliosis progressed after the age of 14 years. Noninvasive mechanical ventilation was introduced due to respiratory impairment at 15 years. During 8 months with respiratory impairment, his body weight decreased from 40.3 kg to 33.4 kg. He was referred to our hospital for vomiting and hematemesis. Radiographic studies indicated a diagnosis of SMA syndrome. Enteral nutrition with a nasojejunal tube successfully treated SMA syndrome for 5 months and his body weight increased from 32.7 kg to 36.1 kg. Gastrostomy was subsequently performed and no recurrence was evident. SMA syndrome is caused by compression of the third part of the duodenum at the angle between the aorta and SMA. The conditions for duodenal vascular compression are weight loss resulting in depletion of the retroperitoneal fat and progressive lordosis. The reasons for SMA syndrome with our patient were weight loss and progressive lordoscoliosis. A conservative approach with enteral nutrition promoted weight gain, increasing retroperitoneal fat. Enteral nutrition should be considered for the treatment of SMA syndrome as a complication of DMD.

Effects and limits of acute noninvasive positive pressure ventilation in children with severe motor and intellectual disabilities with pneumonia/bronchitis.

Objective: We have frequently applied noninvasive positive pressure ventilation (NPPV) to treat acute respiratory failure in children with severe motor and intellectual disabilities. We investigated the features and causes of conditions requiring endotracheal intubation. We aimed to determine whether phlegm expulsion using appropriate breathing physiotherapy with NPPV could avoid the need for endotracheal intubation in such patients. Methods: Between December 2010 and November 2012, 21 children with 51 episodes of acute respiratory failure were placed on NPPV at our hospital. We investigated the ratio, background, and causes of conditions requiring endotracheal intubation. Results: Pneumonia and bronchitis caused 30 and 21 episodes of respiratory failure, respectively. Respiratory infection required endotracheal intubation in 8 of 30 episodes of pneumonia, and in none of the 21 episodes of bronchitis. Respiratory infections were caused by upper airway obstruction with large amounts of secretion (n=4), lower airway obstruction due to atelectasis (n=3) and a combination of both (n=1). The frequency of breathing physiotherapy was significantly higher for all patients who required assistance with active phlegm expulsion than in those who did not (p=0.006). More patients on endotracheal intubation also required phlegm aspiration compared with other patients (p=0.019). Conclusion: We applied NPPV to acute respiratory failure in children with severe motor and intellectual disabilities. This allowed 84% of them to avoid endotracheal intubation. Acute respiratory failure did not improve in any patient who required endotracheal intubation, but we also used NPPV with breathing physiotherapy and postural drainage. Assistance with phlegm expulsion is hampered in children with severe motor and intellectual disabilities due to conditions such as thoracic deformations, joint contracture and glossoptosis. We consider that assistance with phlegm expulsion using appropriate breathing physiotherapy with NPPV is very important for such patients.

A patient with Joubert syndrome who developed sleep-related breathing disorder at 15 years of age.

Joubert syndrome is characterized by neonatal breathing disorders that are thought to improve with age, but recent findings indicate that sleep-related breathing disorders can occur even after infancy. A 15-year-old boy who had a breathing disorder during the neonatal period developed mental retardation and hypotonia. He was diagnosed with Joubert syndrome based on the clinical course and molar tooth sign on brain MRI at 9 years of age. Daytime sleepiness developed at 15 years of age. An interview and the results of sleep questionnaires (Epworth sleepiness scale, Pediatric sleep questionnaire and Pittsburgh sleep quality index), indicated that the patient had daytime sleepiness and a sleep-related breathing disorder. Overnight polysomnography showed central apnea with an apnea hypopnea index of 16, indicating that the patient had central sleep apnea syndrome. After nighttime oxygen therapy at home for one month, the sleep questionnaires showed improved daytime sleepiness and the sleep-related breathing disorder. The improvement persisted for over 12 months thereafter. Sleep-related breathing disorders could be indicated by non-specific complaints such as daytime sleepiness and lead to appropriate therapies. Such disorders should be considered as a complication of Joubert syndrome even after infancy.

Severe acute abdomen caused by symptomatic Meckel's diverticulum in three children with trisomy 18.

Meckel's diverticulum (MD) is the most prevalent congenital anomaly of the gastrointestinal tract and often presents a diagnostic challenge. Patients with trisomy 18 frequently have MD, but the poor prognosis and lack of consensus regarding management for neonates has meant that precise information on the clinical manifestations in infants and children with MD is lacking. We describe the cases of three children with trisomy 18 who developed symptomatic MD. Intussusception was diagnosed in Patient 1, intestinal volvulus in Patient 2, and gastrointestinal bleeding in Patient 3. All three patients underwent surgical treatment and only the Patient 1 died due to pulmonary hypertensive crisis. The other two patients experienced no further episodes of abdominal symptoms. In patients with trisomy 18, although consideration of postoperative complications and prognosis after surgical treatment is necessary, symptomatic MD should carry a high index of suspicion in patients presenting with acute abdomen.

[Effectiveness of continuous infusion of tizanidine (Ternelin) via a feeding tube for patients with the mixed type of tetraplegia].

OBJECTIVE: Severe muscle hypertonia in patients with the mixed type of tetraplegia may be associated with significant deterioration in the quality of life of the patients. Intermittent use of oral muscle relaxant drugs, for example, Tizanidine (Ternelin), which is a fast-acting muscle relaxant, can provide relief from the severe hypertonia in these patients, but only for short durations. METHODS: We conducted a retrospective study of the effect of continuous infusion of tizanidine via a feeding tube on the severe systemic muscle hypertonia in patients with the mixed type of tetraplegia. We mixed tizanidine with milk or other enteral nutrients and administered the mixture via a naso-duodenal tube at a constant infusion rate several hours to 5 patients with the mixed type of tetraplegia showing severe uncontrolled systemic hypertonia under intermittent treatment with oral muscle relaxant drugs. RESULTS: Significant relief from the systemic muscle hypertonia was obtained in 4 of the 5 patients with improvement of the quality of life of the patients, e. g., they could get adequate sleep. There were no serious side effects in any of the cases. CONCLUSION: We consider that continuous infusion of tizanidine via a feeding tube would be useful for the treatment of severe systemic hypertonia in patients in whom the symptom cannot be adequately controlled by intermittent use of oral muscle relaxant drugs.

[Status of children with food allergy who were prescribed an adrenaline autoinjector (epipen)].

PURPOSE: Both to evaluate the characteristics of food allergic children who were prescribed an adrenaline autoinjector and to assess whether it was used appropriately. METHODS: The characteristics of food allergic children who were prescribed an adrenaline autoinjector were investigated. Among these children, those who experienced severe anaphylaxis due to inadvertent ingestion were analyzed, as was whether and how the autoinjector was used. RESULTS: An adrenaline autoinjector was prescribed to 139 food allergic children, most often for egg, followed by milk and wheat allergies. Concomitant bronchial asthma, atopic dermatitis, and food allergies of other causes were present in 49 (35.3%), 68 (48.9%), and 102 cases (73.4%), respectively. The most frequent organ involved in anaphylaxis was the skin (94.2%), followed by the respiratory (78.5%), digestive (28.1%), and circulatory (24.8%) organs. A total of 24 cases experienced severe anaphylaxis after the prescription; however, the autoinjector was used in only six (25%) of those cases. The reasons given for lack of use included fear of use, unavailability of the autoinjector, prior improvement with use of an oral antihistamine and immediate visit to a hospital emergency department in eight, five, three and one case, respectively. CONCLUSION: These results suggest that the autoinjector is often not used appropriately after prescription. Therefore, children and their caregivers require more effective guidance on proper adrenaline autoinjector use.

Efficacy of pyruvate therapy in patients with mitochondrial disease: a semi-quantitative clinical evaluation study.

BACKGROUND: Disorders of oxidative phosphorylation (OXPHOS) cause an increase in the NADH/NAD(+) ratio, which impairs the glycolysis pathway. Treatment with pyruvate is expected to decrease the ratio and thereby restore glycolysis. There are some case reports on the efficacy of pyruvate treatment for mitochondrial diseases. However, few of these reports assessed their results using a standardized scale. METHODS: We monitored 4 bedridden patients with OXPHOS disorders who continued therapies of 0.5-1.0 g/kg/day of sodium pyruvate for more than 12 months. The efficacies of these treatments were evaluated with the Newcastle Pediatric Mitochondrial Disease Scale and the Gross Motor Function Measure with 88 items. RESULTS: The ages of the patients at the treatment initiation ranged from 8-100 months. Of the 4 patients, 3 exhibited improvements within 1-3 months from the initiation of treatment. Among these 3 patients, one maintained the improvement for over 2 years. The remaining 2 regressed 3-6 months after the initiation of treatment. The blood lactate/pyruvate ratios did not correlate with the efficacy of treatment. CONCLUSION: Pyruvate was effective even in bedridden patients with OXPHOS disorders, at least in the short term. Clinical trials with more patients and less severe disabilities are necessary to evaluate the long-term efficacy of this treatment. Biomarkers other than lactate and pyruvate need to be identified to biochemically monitor the efficacy of this treatment.

Pathological fracture and pyogenic osteomyelitis in a patient with type 2 Gaucher disease.

In Gaucher disease (GD), enzyme replacement therapy (ERT) results in the alleviation of hematological abnormalities and visceral infiltration as well as improvement in quality of life and life-span. However, several years may be required for skeletal manifestations, which are usually observed in type 1 and 3 GD, to respond to ERT. Infants with type 2 GD rarely present skeletal manifestations because most of these patients die within the first 2 years of life before they develop skeletal involvement. The use of ERT may prolong the lifespan of these patients and influence the natural history of the disease. The present study reports a new natural history of treated GD in which a 2-year and 7-month-old girl with type 2 GD who was receiving ERT developed valproate-induced Fanconi syndrome, pathological fractures, and pyogenic osteomyelitis. In conclusion, skeletal disease may occur in any type of GD, and Fanconi syndrome may lead to severe skeletal complications in patients with GD.

[Changes in serum levels of selenium, zinc and copper in patients on a ketogenic diet using Ketonformula].

OBJECTIVE: Ketogenic diets tend to cause trace mineral deficiencies. Ketonformula is a foumula for a ketogenic diet developed by Meiji Co Ltd in Japan. No reports are available on the trace mineral deficiencies associated with a use of Ketonformula. METHODS: We monitored the serum levels of selenium, zinc and copper as well as the amount of the daily intake of these minerals before and at 6 months after the initiation of the ketogenic diet with Ketonformula in six patients with intractable epilepsy associated with severe motor and intellectual disabilities. RESULT: The median serum selenium concentration decreased from 7.0 (range, 6.5-12.3) microg/dl to 6.2 (5.4-10.9) microg/dl as a result of the 6-month-treatment with Ketonformula (p < 0.05, Wilcoxon signed-rank test). The median daily selenium intake decreased from 17.8 (15.0-27.0) microg/day at the baseline to 5.5 (5.0-22.0) microg/day after 6 months on the diet (p < 0.05). The median serum zinc concentration increased slightly (from 66.0 (46.0-84.0) microg/dl to 68.0 (46.0-71.0) microg/dl), but the difference was not significant. The median daily zinc intake, however, significantly decreased from 4.2 (3.7-6.0) mg/day to 2.2 (2.0-3.0) mg/day (p < 0.05). The median serum copper concentration also showed no significant decrease (from 134.5 (119.0-168.0) microg/dl to 126.0 (86.0-183.0) microg/dl). The median daily copper intakes, however, decreased significantly from 0.80 (0.35-1.30) mg/day to 0.30 (0.26-0.40) mg/day (p < 0.05). CONCLUSIONS: The decline of the serum selenium concentrations and daily enteral intakes of selenium, zinc, and copper after 6 months on Ketonformula suggested that patients on this ketogenic formula needs close monitoring as well as supplementation of these trace minerals.

Reversible splenic lesion in a patient with Febrile Infection-Related Epilepsy Syndrome (FIRES).

Febrile infection-related epilepsy syndrome (FIRES) is a severe epileptic syndrome that manifests with refractory seizures or status epilepticus in previously healthy children after banal febrile illness. The neuroimaging findings in the acute phase of FIRES are nonspecific or normal. We report the case of a 7-year-old boy with FIRES who presented with a reversible lesion in the splenium of the corpus callosum on brain magnetic resonance imaging (MRI). The patient developed clusters of clonic seizures with a deviation of the eyes after a 3-day history of fever. A reversible splenial lesion was observed on brain MRI and, therefore, the initial diagnosis was mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). However, the intractable complex partial seizures necessitated a long-term midazolam infusion, indicating that FIRES was a more likely diagnosis than MERS. All other findings of this patient met the diagnostic criteria for FIRES. With this diagnosis, a high-dose phenobarbital was administrated, and the seizures were successfully controlled. This case indicated that FIRES should be considered even in patients with a reversible splenial lesion associated with encephalitis/encephalopathy.

Glycemic index treatment using Japanese foods in a girl with Lennox-Gastaut syndrome.

We introduced a low glycemic index treatment using Japanese ethnic foods to a 13-year-old girl with Lennox-Gastaut syndrome caused by tuberous sclerosis complex. She had previously refused the modified Atkins diet within 2 weeks of diet treatment because of its restrictiveness. The low glycemic index treatment was implemented by limiting the daily carbohydrate intake to 50 g of foods with a glycemic index of less than 50 relative to that of glucose, which included udon, soba, and unpolished Japonica rice with natto. One month after the initiation of the diet therapy, the clusters of tonic seizures for 30 to 60 minutes during sleep were reduced from two or three times per week to once or twice per month, and the frequent myoclonic seizures in the awake state disappeared. She has been on the diet therapy for more than 1 year, and the efficacy of the diet has been sustained. Low glycemic index treatment should be considered for patients with medication-resistant epilepsy who cannot tolerate restrictive diet therapies. Japanese ethnic foods can be used for this diet therapy.

Passive toothbrushing-induced seizures: report of a severely disabled girl.

Toothbrushing-induced seizures are rare reflex seizures triggered by the brushing of one's own teeth. We encountered an 11-year-old girl with severe mental retardation, hypotonic cerebral palsy and epilepsy who presented with toothbrushing-induced seizures. She had had spontaneous brief tonic seizures several times a day since the age of 1 year and 2 months and started presenting with the same type of seizures induced by toothbrushing from the age of 8 years. As she could not brush her teeth by herself due to her disabilities, her mother brushed her teeth daily for her. The interictal EEG showed spike-and-wave complexes in the frontal regions bilaterally. The [Tc-99m]HMPAO-SPECT at the time of the seizure induced by toothbrushing suggested that the seizures originated from the left perisylvian cortex. This is the first report of toothbrushing-induced seizures triggered by the brushing of the patient's teeth by another person ('passive toothbrushing').

Grisel syndrome as a complication of Kawasaki disease: a case report and review of the literature.

UNLABELLED: Grisel syndrome is a non-traumatic atlantoaxial subluxation and a rare complication of any inflammatory condition of the upper neck and otolaryngological procedures. Delayed diagnosis causes neurological impairment, ranging from radiculopathy to paralysis and death. Kawasaki disease is a very frequent and important acute febrile vasculitis of childhood that is seen worldwide, and upper neck involvement (cervical lymphadenopathy) is one of the common symptoms of Kawasaki disease. A case of Grisel syndrome that occurred as a complication of Kawasaki disease is reported. This is the first case report, in English, of Grisel syndrome as a complication of Kawasaki disease. CONCLUSION: Pediatricians should be aware of Grisel syndrome as a possible complication of Kawasaki disease.

[Efficacy, safety and tolerability of high-dose topiramate with rapid dose titration in symptomatic West syndrome].

OBJECTIVE: We investigated the efficacy, safety, and tolerability of high-dose topiramate with rapid dose titration in 12 children with symptomatic West syndrome who suffered from severe motor and intellectual disabilities. METHODS: Topiramate was introduced as add-on therapy at the daily dose of 1 mg/kg/day, followed by increments of 2 mg/kg at 3- or 4-day intervals, up to a maximum of 19 or 20 mg/kg/day. The ages at the start of topiramate therapy ranged from 5 to 22 months. Prior to the topiramate therapy, the patients had received 2 to 6 antiepileptic agents with (8 patients) or without ACTH (4 patients). RESULTS: Topiramate appeared to be effective in 8 of the 12 patients (67%); four became seizure-free;three showed greater than 90% seizure reduction; one showed greater than 50% seizure reduction. The maintenance dose was 7 to 20 mg/kg/day (mean:17.9 +/- 3.9 mg/kg/day). In 4 of these 8 patients (50%), the spasms relapsed several months after complete cessation or diminution in the frequency of the spasms following treatment with topiramate. All of the 8 topiramate-responsive patients could continue the topiramate therapy throughout this study. The duration of topiramate therapy was 7 to 42 months (median: 12.5 months). There were no severe side effects that necessitated discontinuation of topiramate, including kidney stones. CONCLUSIONS: High-dose topiramate with rapid dose titration was revealed to be effective, safe, and well-tolerated in children with symptomatic West syndrome.