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Ito M.,Ehime University | Fukuda M.,Ehime University | Suzuki Y.,Ehime Rehabilitation Center for Children | Wakamoto H.,Ehime Rehabilitation Center for Children | Ishii E.,Ehime University
BMC Pediatrics | Year: 2017

Background: Long-term treatment with antibiotics containing pivalic acid may decrease serum carnitine concentration and can sometimes be associated with severe hypoglycemia and encephalopathy in infants. Little has been reported, however, on severe hypocarnitinemia induced by acute administration in older children. Case presentation: We describe a 6-year-old Japanese girl with Fukuyama-type congenital muscular dystrophy who lost consciousness after 3 days of treatment with an antibiotic containing pivalic acid (cefditoren pivoxil). Investigations at the onset of unconsciousness revealed hypoglycemia (free plasma glucose concentration: 31 mg/dL) and hypocarnitinemia (serum free carnitine concentration: 6.2 μmol/L). Intravenous administration of glucose rapidly improved her symptoms without any complications. Serum free carnitine concentration was 29.0 μmol/L immediately prior to the initiation of cefditoren pivoxil. Computed tomography scanning showed severe peripheral skeletal muscle atrophy, indicating the likelihood of decreased carnitine stores in skeletal muscle. Conclusions: Although serum carnitine concentration can appear deceptively normal, skeletal muscle carnitine stores can be reduced in patients with severe muscular atrophy. Even a short course of a pivalate-containing antibiotic can lead to life-threatening hypocarnitinemia in older children with severe muscular dystrophy. © 2017 The Author(s).


PubMed | Ehime Rehabilitation Center for Children, National Hospital Organization Shikoku Cancer Center, National Hospital Organization Minami Kyushu Hospital, Ehime Prefectural Central Hospital and 2 more.
Type: Journal Article | Journal: The Journal of pediatrics | Year: 2015

To determine whether the serum level of Krebs von den Lungen-6 (KL-6), a circulating high-molecular weight glycoprotein and a diagnostic biomarker of interstitial lung diseases, is a clinically useful biomarker for detecting chronic aspiration in children with severe motor and intellectual disabilities (SMIDS).Children with SMIDS undergoing videofluorography for assessment of dysphagia were prospectively evaluated. Based on the videofluorography results, the participants were classified into aspiration and non-aspiration groups. Age, sex, white blood cell count, and serum levels of C-reactive protein, lactate dehydrogenase, albumin, and KL-6 were compared between the 2 groups. Binary logistic regression was performed to identify factors independently associated with the presence of aspiration.A total of 66 patients participated in this study, 37 who were classified as the aspiration group and 29 as the non-aspiration group. The serum KL-6 level in the aspiration group was significantly higher than that in the non-aspiration group (median, 344 U/mL vs 207 U/mL, P < .01). Logistic regression modeling showed that the number of prescribed antiepileptic drugs (OR, 1.978; 95% CI, 1.217, 3.214; P < .01) and serum KL-6 level (OR, 1.012; 95% CI, 1.005, 1.019; P < .01) were independent predictors of aspiration.The study demonstrated that the KL-6 level is significantly higher in children with SMIDS who aspirate than in those who do not. KL-6 shows promise as a biomarker for chronic lung disease due to aspiration in these children.


Wakamoto H.,Ehime Prefectural Central Hospital | Wakamoto H.,Ehime Rehabilitation Center for Children | Takahashi Y.,Shizuoka Institute of Epilepsy and Neurological Disorders | Ebihara T.,Ehime Prefectural Central Hospital | And 4 more authors.
Brain and Development | Year: 2012

Acute encephalitis with refractory, repetitive partial seizures (AERRPS) is a neurologic syndrome characterized by extraordinarily frequent and refractory partial seizures, which immediately evolve into refractory epilepsy. To elucidate the pathophysiology of AERRPS, we performed an immunologic study of an affected boy, revealing decreased natural killer (NK) cell activity in the peripheral blood mononuclear cells. IgG antibodies against the glutamate receptor (GluR)ε2, ζ1, and δ2 subunits were all positive in both the serum and cerebrospinal fluid (CSF). There were raised plasma concentrations of interleukin (IL)-2, IL-6, IL-10, tumor necrosis factor-α, and interferon-γ as well as an extremely elevated CSF level of IL-6. These findings suggest that AERRPS is immune-mediated encephalitis, in which both autoimmunity and exaggerated cytokine production are involved. NK cell dysfunction may be the underlying abnormality in this AERRPS case, which might have contributed to the production of GluR autoantibodies. © 2012 The Japanese Society of Child Neurology.


PubMed | Ehime University, Ehime Rehabilitation Center for Children, Ehime Prefectural Central Hospital and Sumitomobesshi Hospital
Type: Journal Article | Journal: Pediatrics international : official journal of the Japan Pediatric Society | Year: 2015

The aim of this study was to assess the importance of KL-6 level in evaluating the status of stabilized chronic pneumonia in children in the severe motor and intellectual disabilities-medical care-dependent (SMID-MCD) category.A total of 20 SMID-MCD children were enrolled in this study. Serum KL-6, white blood cell count, C-reactive protein, chest computed tomography (CT) and other factors related to respiratory complications were analyzed in all children under stable respiratory conditions.Mean age was 5.8 1.0 years (mean SE). Serum KL-6 was significantly higher in those SMID-MCD children with abnormal CT than in those with normal CT: 316 39 U/mL versus 190 11, respectively (P = 0.0075).Measures of serum KL-6 level provide valuable information for determining the respiratory management of SMID-MCD children with occult chronic pneumonia.


Shigemi R.,Matsuyama Shimin Hospital | Fukuda M.,Ehime University | Suzuki Y.,Ehime University | Morimoto T.,Ehime Rehabilitation Center for Children | Ishii E.,Ehime University
Brain and Development | Year: 2011

We report a case involving a 15-year-old boy with MELAS (G13513A mutation) who developed several stroke-like episodes in a short period of time. Intravenous administration of l-arginine during the acute phase of the stroke-like episodes reduced symptoms immediately, and oral supplementation of l-arginine successfully prevented further stroke-like episodes. This is the first report on effective l-arginine therapy in MELAS associated with the G13513A mutation. © 2010 The Japanese Society of Child Neurology.


Fukuda M.,Ehime University | Suzuki Y.,Ehime University | Hino H.,Ehime University | Kuzume K.,Ehime Prefectural Niihama Hospital | And 2 more authors.
Epilepsia | Year: 2010

Theophylline-associated seizures (TAS) often progress to prolonged or treatment-resistant convulsions. Theophylline is a nonselective adenosine receptor antagonist. Adenosine is an endogenous anticonvulsant that can terminate seizures. Fever and young age have been reported to be risk factors for TAS. To elucidate the mechanism of TAS, we investigated the effect of theophylline and adenosine receptor ligands on hyperthermia-induced seizures in juvenile rats. The treatment dose of theophylline or control saline was injected intraperitoneally 1 h before hyperthermia-induced seizures. The seizure threshold in the theophylline group was significantly lower and seizure duration was significantly longer than those in the control group. The addition of a selective adenosine A1 receptor agonist and an adenosine kinase inhibitor completely counteracted the effects of theophylline. Moreover, a selective A1 antagonist caused a significantly longer seizure duration compared with the control. These findings suggest that blockage of the adenosine A1 receptor is the main cause of TAS. © 2009 International League Against Epilepsy.


Suzuki Y.,Ehime University | Kobayashi M.,Ehime University | Kuwabara K.,Ehime University | Kawabe M.,Ehime University | And 2 more authors.
Brain and Development | Year: 2013

Patients with severe motor and intellectual disabilities (SMID) often suffer from autonomic nervous system disturbances. At the same time, the caregivers of patients with SMID face challenges to understand the patients' chronic health problems effectively by simply observing them. Therefore, recognizing specific symptoms is important to improve support for SMID. We investigated the autonomic nervous function in patients with SMID with skin vasomotor responses to cold stimuli. The relationship of the results of cold stress and autonomic symptoms observed by the main caretakers was also examined. We analyzed 38 patients with SMID. Their hand skin temperature was measured before and after cold stimuli using infrared thermography. A 'distal-dorsal difference' (DDD) at baseline, and the recovery rate of the second fingertip and dorsum were calculated. All main caregivers filled out questionnaires evaluating autonomic symptoms. The recovery rate of the second fingertip and dorsum after cold stimuli was lower than 80% in 64% and 60% patients, respectively. The baseline DDD was greater than 1 °C in 84% of the patients. A DDD > 1 °C was associated with a reduced recovery rate. All caregivers recognized some autonomic-related symptoms. Patients with constipation or snoring demonstrated a reduced recovery rate. However, none of the observed symptoms can predict the presence of a reduced rate with cold stimuli in a statistically significant way. This study showed excessive sympathetic nerve activities in patients with SMID. The baseline DDD could be a valuable parameter accessing their microvascular circulation. To improve the life of a person with SMID, accessing autonomic function using a noninvasive method, such as thermography is warranted without directly observed symptoms. © 2012 The Japanese Society of Child Neurology.


Fukuda M.,Ehime University | Kawabe M.,Ehime University | Takehara M.,Ehime University | Iwano S.,Ehime University | And 6 more authors.
Brain and Development | Year: 2015

Background: Carnitine deficiency is relatively common in epilepsy; risk factors reportedly include combination antiepileptic drug (AED) therapy with valproic acid (VPA), young age, intellectual disability, diet and enteral or parenteral feeding. Few studies have examined the correlation between each risk factor and carnitine deficiency in children with epilepsy. We examined the influence of these risk factors on carnitine deficiency, and identified a formula to estimate plasma free carnitine concentration in children with epilepsy. Methods: Sixty-five children with epilepsy and 26 age-matched controls were enrolled. Plasma carnitine concentrations were measured using an enzyme cycling assay, and correlations were sought with patients' other clinical characteristics. Results: Carnitine deficiency was found in approximately 17% of patients with epilepsy and was significantly associated with carnitine-free enteral formula only by tube feeding, number of AEDs taken (independent of VPA use), body weight (BW), body height and Gross Motor Function Classification System (GMFCS) score. Stepwise multiple linear regression analysis indicated that carnitine concentration (in μmol/L) could be accurately estimated from a formula that does not require blood testing: 42.44+0.14×(BW in kg)-18.16×(feeding)-3.19×(number of AEDs), where feeding was allocated a score of 1 for carnitine-free enteral formula only by tube feeding and 0 for taking food orally (R2=0.504, P<0.001). Conclusions: Carnitine-free enteral formula only by tube feeding, multiple AED treatment and low BW are risk factors for carnitine deficiency in children with epilepsy l-carnitine should be administered to children at risk of deficiency to avoid complications. Treatment decisions can be informed using an estimation formula that does not require blood tests. © 2014 The Japanese Society of Child Neurology.


Fukuda M.,Ehime University | Suzuki Y.,Ehime University | Hino H.,Ehime University | Morimoto T.,Ehime Rehabilitation Center for Children | Ishii E.,Ehime University
Seizure | Year: 2011

Adenosine is a potent neuromodulator in the central nervous system (CNS). The functional deterioration of adenosine A1 receptors in the CNS was reported to cause a failure of termination of seizures and to a lower seizure threshold of hyperthermia-induced seizures (HS) in childhood rats, which may contribute to adenosine-related convulsive disorders such as theophylline-associated seizures in childhood patients. In contrast to the inhibitory effect of adenosine A1 receptors, the function of adenosine A2A receptors remains controversial. To clarify the function of adenosine A2A receptors in childhood convulsive disorders associated to hyperthermia, we investigated the in vivo interaction between adenosine A2A receptors and their ligands in HS in childhood rats. Adenosine selective A2A receptor ligands were injected intraperitoneally before HS. We measured brain temperature at the onset of seizures and the mortality rate after HS. We found that brain temperature at seizure onset was significantly higher in the A2A receptor antagonist group compared with that in the control group (p < 0.05), and there was no significant difference in mortality among the groups. In contrast, brain temperature at seizure onset was significantly lower in the A2A receptor agonist group compared with that in the control group (p < 0.05), and mortality was significantly higher in the A2A agonist group compared with that in the control group (p < 0.001). The activation of the adenosine A2A receptor might enhance seizures associated to hyperthermia in the childhood human brain, and be involved in the pathogenesis of sudden unexpected death in epilepsy (SUDEP) in childhood patients with convulsive disorders. © 2010 British Epilepsy Association.


PubMed | Ehime University, Ehime prefectural Niihama Hospital, Ehime prefectural Imabari Hospital and Ehime Rehabilitation Center for Children
Type: | Journal: Blood cells, molecules & diseases | Year: 2016

Gaucher disease is a lysosomal storage disease caused by deficiency of glucocerebrosidase and accumulation of glucocerebroside. Three major sub-types have been described, type 2 is an acute neurological form that exhibits serious general symptoms and poor prognosis, compared with the other types. This case was a girl diagnosed with type 2 Gaucher disease at 12months of age who presented with poor weight gain from infancy, stridor, hypertonia, hepatosplenomegaly, trismus and an eye movement disorder. Enzyme replacement therapy (ERT) was administered, but she had frequent myoclonus and developmental regression. She needed artificial ventilation because of respiratory failure. She died at 11years of age. An autopsy demonstrated infiltrating CD68-positive large cells containing abundant lipids in alveoli, while in the liver, kidney and bone marrow CD68-positive cells were small and round. In the bone marrow, myelodysplastic changes were present without Gaucher cells. The infiltration of Gaucher cells in alveoli was marked, suggesting that ERT was relatively ineffective in pulmonary involvement, particularly intra-alveolar. Additional treatments are necessary to improve the neurological and pulmonary prognosis of type 2Gaucher disease.

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