Successful control of radicular pain in a pediatric patient with Guillain-Barré syndrome.

A 10-year-old boy was diagnosed as having the axonal form of Guillain-Barré syndrome (GBS). The patient noticed progressive weakness of the lower legs on the 1st day of illness. Intravenous immunoglobulin therapy was immediately started on the 2nd day of illness. Despite the favorable recovery of muscle weakness, he complained of severe needle-like pain in the thighs and buttocks and also painful numbness over the gastrocnemius regions. Acetaminophen and hydroxyzine therapy was ineffective for the pain control. Oral prednisolone therapy (0.7 mg/kg/day) led to drastic pain-relief with favorable improvement of the weakness. Corticosteroid therapy is not typically used in the management of GBS patients. Although GBS-associated pain frequently occurs in children, only a few reports have indicated the analgesic utility of steroids in the treatment of pediatric GBS. This observation may suggest the alternative of this therapy as for the as the limited, but potentially rapid, control of GBS-associated acute radicular pain in pediatric patients.

A nationwide survey of opsoclonus-myoclonus syndrome in Japanese children.

BACKGROUND: Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disease characterized by opsoclonus, myoclonus, ataxia, and behavioral changes. The aim of our study was to investigate the epidemiological characteristics of OMS in Japan and to clarify the association between therapy and prognosis. METHODS: We retrospectively collected the data from 626 Japanese medical institutions from 2005 to 2010, and analyzed the clinical features of pediatric patients with OMS based on the data. RESULTS: In this survey, there were 23 patients (10 males and 13 females). The median ages at the disease onset and the time of study were 16.5 months (range: 11-152 months) and 54 months (range: 24-160 months), respectively. The principal symptoms were opsoclonus (23 patients, 100%), myoclonus (21 patients, 91.3%), and ataxia (23 patients, 100%). The related factors were neuroblastoma (10, 43.5%), infection (9, 39.1%), and immunization (2, 8.7%). The treatments for OMS were included intravenous immunoglobulin (17, 73.9%), methylprednisolone pulse (13, 56.5%), oral prednisolone (12 patients, 52.2%), and chemotherapy and/or operation for the underlying tumors (6, 26.1%), and rituximab (2, 8.7%). Complete remissions were obtained in 35.3%, 23.1%, 33.3%, 66.7%, and 100% of these treatments, respectively. At the latest follow-up period, 8 (34.8%) and 17 patients (73.9%) showed neurological sequelae of motor and intellectual functions, respectively. Patients whose treatment was started more than 30 weeks after the disease onset suffered from the severest neurological sequelae (OMS severity 4) more frequently than those less than 30 weeks (p=0.022). CONCLUSION: The annual incidence of OMS was estimated to be 0.27-0.40 cases per million in Japanese children. More than 70% of OMS patients had neurological sequelae, especially intellectual function. Early effective treatments within 30 weeks after the onset may be required to prevent the serious neurological outcome.

Traumatic head injury mimicking acute encephalopathy with biphasic seizures and late reduced diffusion.

Many studies have reported acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) associated with viral infection at onset, but few studies have reported AESD without infection. We report the case of a 9-month-old boy who had a clinical course mimicking AESD after a traffic accident. The traffic accident caused a mild subdural hematoma without neurological abnormalities on admission. The boy became unconscious on the second day, and he was diagnosed with non-convulsive status epilepticus on the third day. Diffusion-weighted imaging showed reduced water diffusion in the subcortical white matter. On laboratory analysis interleukin (IL)-6 was elevated in the cerebrospinal fluid (CSF), but not in the serum. He had severe neurological sequelae with mental retardation, spastic tetraplegia, and epilepsy. We suggest that brain damage mimicking AESD was caused by the traffic accident and the prolonged seizure during infancy.

Serum levels of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinases-1 in human herpesvirus-6-infected infants with or without febrile seizures.

Human herpesvirus-6 (HHV-6) is a cause of exanthema subitum and, sometimes, of febrile seizures. However, the pathogenesis of febrile seizures associated with HHV-6 infection remains unclear. We investigated serum matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels in infants with HHV-6 infection. Serum levels of both MMP-9 and TIMP-1 were significantly higher in infants with HHV-6 infection than in controls. Serum TIMP-1 levels were significantly higher in infants with febrile seizures than in infants without febrile seizures. Serum MMP-9/TIMP-1 ratios were significantly lower in infants with febrile seizures than in infants without febrile seizures. In infants with HHV-6 infection, positive correlations were found between serum MMP-9 concentrations and the white blood cells (WBC) count, and between serum TIMP-1 concentrations and the WBC count. Positive correlations were also found between the amounts of HHV-6 DNA and the ratios of MMP-9/TIMP-1 in infants with HHV-6 infection. In conclusion, we suggest that high serum levels of MMP-9 and TIMP-1 in infants with HHV-6 infection may induce dysfunction of the blood-brain barrier, eventually causing febrile seizures.

Effectiveness of laryngotracheal separation in neurologically impaired pediatric patients.

CONCLUSION: Laryngotracheal separation (LTS) can prevent aspiration pneumonia, improve the respiratory condition, and offer the possibility of home care for neurologically impaired children. OBJECTIVES: This study aimed to evaluate the effectiveness of LTS in neurologically impaired pediatric patients from the viewpoint of postoperative success of pneumonia prevention, improvement in the respiratory condition, and postoperative success rate of home-based care. METHODS: The medical records of 21 children who underwent LTS at an academic medical center from September 2004 to March 2013 were retrospectively investigated. Pre- and postoperative data, including the frequency of pneumonia treatment, the frequency of sputum suctioning, the respiratory condition, the nutrition method, and the outcome after LTS were assessed. We also used the scoring system for patients with severe motor and intellectual disabilities, medical care dependent group (SMID-MCDG) in Japan for evaluating the usefulness of LTS. RESULTS: The frequency of pneumonia treatment and that of suctioning decreased considerably after LTS. Furthermore, the respiratory condition improved at a rate of 63.19%. The SMID-MCDG score significantly reduced after LTS. No significant complications were observed and two-thirds of the patients were successfully discharged for home care after the procedure.

An 11-year-old girl with recurrent bacterial meningitis due to liquorrhea caused by bone malformation of the skull base.

The patient is a healthy 11-year-old girl with no history of trauma or hearing impairment. She developed pneumococcal meningitis three times, at ages 7, 10, and 11. Intracranial examination revealed, pore expansion and cerebrospinal fluid leakage in the right internal acoustic foramen, which were attributed to a bone malformation of the base of the skull. A procedure was performed to close the cerebrospinal fluid leakage; no relapse has been observed thus far. Previous case reports indicate that repetitive bacterial meningitis is often caused by internal ear malformation, trauma, tumors, or surgical operation. This case suggests the possibility that underlying disorders may not be apparent in cases of repetitive bacterial meningitis and, more proactive investigations are required to prevent further recurrence of meningitis.

Tau protein concentrations in the cerebrospinal fluid of children with acute disseminated encephalomyelitis.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is clinically characterized by the acute onset of neurological symptoms after a viral infection or immunization, and is thought to represent an autoimmune disease directed against myelin. Tau protein is a phosphorylated microtubule-associated protein, primarily located in neuronal axons. Increased levels of tau protein in cerebrospinal fluid (CSF) are found in various pathological conditions. METHODS: We used tau protein as a marker of axonal damage and examined its concentration in the CSF of 27 children with ADEM. RESULTS: CSF tau protein concentration in children with ADEM was significantly higher than that in the CSF of control subjects (P=0.008). There were no significant differences in CSF tau protein concentrations in the ADEM patients with and without encephalopathy. The CSF tau protein concentration in patients with partial lesion resolution in follow-up brain MRI was significantly higher than in patients with complete lesion resolution (P=0.014). CONCLUSIONS: In conclusion, we demonstrated that CSF tau protein concentration was significantly increased in ADEM patients. Our findings suggest that axonal damage may occur in addition to demyelination in children with ADEM.

High mobility group box 1 in patients with 2009 pandemic H1N1 influenza-associated encephalopathy.

BACKGROUND: Patients with 2009 pandemic H1N1 influenza-associated encephalopathy (pIE) have been reported in Japan. The most common clinical symptoms of this condition are seizures and progressive coma with high-grade fever. We previously highlighted the cytokine profile of pIE; our results suggest that proinflammatory cytokines play an important role in the pathogenesis. High mobility group box 1 (HMGB1) protein is a late mediator of inflammation or sepsis. However, there are few reports regarding the serum and cerebrospinal fluid (CSF) levels of HMGB1 in pIE patients. METHODS: We measured serum and CSF levels of HMGB1 in the following: pIE patients with poor outcomes, pIE patients without neurological sequelae, influenza patients without pIE, and control subjects. RESULTS: Serum HMGB1 levels were significantly higher in pIE patients with poor outcomes compared to those without neurological sequelae. In contrast, there was no difference in CSF HMGB1 levels among all groups. Regarding pIE patients, we found a significant positive correlation between HMGB1 levels and IL-6 in the serum but not in the CSF. CONCLUSIONS: Our results suggest that HMGB1 protein may be involved in the pathogenesis of pIE and that a high serum, but not CSF, level of inflammatory cytokines plays an important role in the severity of pIE.

Serum and cerebrospinal fluid levels of visinin-like protein-1 in acute encephalopathy with biphasic seizures and late reduced diffusion.

BACKGROUND: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) has recently been recognized as an encephalopathy subtype. Typical clinical symptoms of AESD are biphasic seizures, and MRI findings show reduced subcortical diffusion during clustering seizures with unconsciousness after the acute phase. Visinin-like protein-1 (VILIP-1) is a recently discovered protein that is abundant in the central nervous system, and some reports have shown that VILIP-1 may be a prognostic biomarker of conditions such as Alzheimer's disease, stroke, and brain injury. METHODS: However, there have been no reports regarding serum and cerebrospinal fluid (CSF) levels of VILIP-1 in patients with AESD. We measured the serum and CSF levels of VILIP-1 in patients with AESD, and compared the levels to those in patients with prolonged febrile seizures (FS). RESULTS: Both serum and CSF levels of VILIP-1 were significantly higher in patients with AESD than in patients with prolonged FS. Serum and CSF VILIP-1 levels were normal on day 1 of AESD. CONCLUSIONS: Our results suggest that both serum and CSF levels of VILIP-1 may be one of predictive markers of AESD.

Serum soluble CD163 levels in patients with influenza-associated encephalopathy.

BACKGROUND: Influenza-associated encephalopathy (IE) is a serious complication during influenza viral infection. Common clinical symptoms of IE include seizures and progressive coma with high-grade fever. We previously reported that hypercytokinemia and monocyte/macrophage activation may play an important role in the pathogenesis of IE. CD163 is a scavenger receptor for hemoglobin-haptoglobin complexes and is expressed by monocytes/macrophages. Proteolytic cleavage of monocyte-bound CD163 by matrix metalloproteinases releases soluble CD163 (sCD163). However, there have been no reports regarding serum sCD163 levels in IE patients. METHODS: We measured serum levels of sCD163 as a marker of monocyte/macrophage activation in IE patients with poor outcomes, those without neurological sequelae, influenza patients without IE, and control subjects. RESULTS: Serum sCD163 levels were significantly higher in IE patients with poor outcomes than in those without neurological sequelae. In particular, sCD163 levels in cases of death were significantly higher than those in other cases. CONCLUSIONS: Our results suggest that monocyte/macrophage activation is related to the pathogenesis of severe IE.

Serum matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 levels in non-herpetic acute limbic encephalitis.

The pathogenesis of non-herpetic acute limbic encephalitis (NHALE) has been not clear. Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) play important roles in the function of the blood-brain barrier. We measured the serum concentrations of MMP-9 and TIMP-1 by using enzyme-linked immunosorbent assay (ELISA) in 23 patients with NHALE in the acute and convalescent stages. Serum MMP-9 concentrations and ratios of serum MMP-9/TIMP-1 were significantly higher (1) in patients with NHALE in acute and convalescent stages than in control patients (all P < 0.001); (2) in patients with NHALE at the acute stage compared with those at the convalescent stage (P = 0.004, and P = 0.014, respectively). In contrast, serum TIMP-1 concentrations were significantly lower in patients with NHALE in the acute and convalescent stages than in control patients (both P < 0.001) but did not differ in patients with NHALE in the acute and convalescent stages. Our preliminary study suggests that the prolonged imbalance of MMP-9 and TIMP-1 is associated with the pathogenesis of NHALE.

Serial cerebrospinal fluid neurofilament concentrations in bacterial meningitis.

Neurofilament (NF) is one of the major cytoskeleton proteins of neurons. We investigated the concentrations of the heavy subunit of NF (NF-H) in cerebrospinal fluid (CSF) as biomarkers of neuronal injury in bacterial meningitis. Concentrations of NF-H in CSF of 26 children with bacterial meningitis and in 16 control subjects were measured by ELISA. The CSF NF-H levels were elevated in 22 of the 26 children (85%) with bacterial meningitis. The peak CSF NF-H level occurred at a median period of 10.5 days after onset of illness (range, 1 to 35 days). The peak CSF NF-H levels of the patients with neurological sequelae (n=4) were significantly higher than those without sequelae (n=22) (7.06 vs. 2.46 ng/mL as median, p=0.048). There was no significant difference in CSF NF-H levels between patients with and without severe neurological sequelae up to day 14 of illness, but the CSF NF-H levels in patients with sequelae were significantly higher than in those without sequelae after day 14 of illness (2.04 vs. 1.19 ng/mL as median, p=0.024). We suggest that neuronal injury occurs in bacterial meningitis regardless of the presence or absence of neurological sequelae.

Clinical characteristics of benign convulsions with rotavirus gastroenteritis.

Convulsions sometimes occur in infants and toddlers with mild gastroenteritis. We retrospectively investigated the hospital records of 106 patients admitted to our hospital who had rotavirus gastroenteritis from February 2002 to April 2008. There were 23 patients with convulsions, including 13 with benign convulsions, 9 with febrile seizures, and 1 with epilepsy. Gastroenteritis in patients with benign convulsions was mild from the viewpoint of body weights and serum creatinine concentrations on admission and the duration of admission. Serum Na(+) and Cl(-) concentrations of patients with benign convulsions were relatively lower than those without convulsions on admission (P = .006, and P = .008, respectively). Twelve of thirteen patients had no other seizures after oral administration of 5 mg/kg of carbamazepine, while 1 patient had 1 convulsion 15 minutes after the therapy. In conclusion, carbamazepine therapy was effective for benign convulsions with rotavirus gastroenteritis.

Mononuclear cell subpopulations in CSF and blood of children with bacterial meningitis.

OBJECTIVES: To elucidate mononuclear cell subsets of the cerebrospinal fluid (CSF) in order to investigate the pathogenesis of bacterial meningitis (BM). METHODS: Mononuclear cell and lymphocyte subsets in CSF and peripheral blood from 10 children with acute-stage BM before treatment on the same day were measured by flow cytometry. The control subjects for the subsets of peripheral blood were 15 healthy children. RESULTS: The percentages of CD14+ monocytes/macrophages (median: 56.5%), activated CD14+CD16+ monocytes/macrophages (20.9%), and CD14+CD16+ cells among total CD14+ cells (37.9%) in the CSF were significantly higher than those in the blood of children with BM (p<0.01, p<0.01, and p<0.05, respectively), which were significantly higher than those of the controls (p<0.001, p<0.001, p<0.05, respectively). The percentages of CD3+ (77.3%), CD4+ (45.2%), and CD8+ T cells (32.6%) in the CSF were significantly higher than those in the blood of affected children (p<0.01, p<0.01, and p<0.05, respectively). The percentages of CD3+, CD4+, and CD8+ T cells in the blood of children with BM were significantly lower than those of controls (all p<0.001). The percentages of CD20+ B cells (6.9%) in the CSF were significantly lower than those in the blood of affected children (p<0.01), which were significantly higher than those of controls (p<0.001). CONCLUSION: The percentages of monocytes/macrophages and T cells in CSF were higher than those in blood in children with BM.

Cerebrospinal fluid levels of cytokines in non-herpetic acute limbic encephalitis: comparison with herpes simplex encephalitis.

BACKGROUND: Recently, non-herpetic acute limbic encephalitis (NHALE) was identified as a new subgroup of limbic encephalitis. The immunological pathophysiology of NHALE is still unclear. METHODS: We measured the concentrations of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), IL-4, IL-6, IL-10, and soluble TNF receptor 1 (sTNFR1) in the cerebrospinal fluid (CSF) of 15 patients with NHALE and 13 with herpes simplex encephalitis (HSE) by cytometric bead array or ELISA. RESULTS: The CSF concentrations of IL-6 in patients with NHALE and IFN-gamma, IL-6, IL-10, and sTNFR1 in HSE patients were significantly higher than those of controls (p<0.001, p=0.004, p<0.001, p=0.018, and p<0.001, respectively). There were significant correlations among CSF IL-6, IL-10, and sTNFR1 levels in HSE patients. The CSF concentrations of IFN-gamma and sTNFR1 levels of patients with HSE were significantly higher than those with NHALE (p=0.001 and p=0.002, respectively). CONCLUSIONS: CSF cytokine levels in NHALE were relatively low compared with those in HSE. These results may be related to the favorable prognosis of NHALE.

Dexamethasone decreases cerebrospinal fluid soluble tumor necrosis factor receptor 1 levels in bacterial meningitis.

It is known that the use of adjunctive dexamethasone in bacterial meningitis reduces audiologic and neurologic sequelae. The cerebrospinal fluid (CSF) level of soluble tumor necrosis factor 1 (sTNFR1) is an important indicator of neurologic sequelae in bacterial meningitis. We measured the CSF levels of IL-6 and sTNFR1 before administration of antibiotics (CSF1) and 1-3 days after administration of antibiotics (CSF2) in nine patients with bacterial meningitis who received dexamethasone sodium and five without dexamethasone. The CSF2 IL-6 levels of patients with/without dexamethasone were significantly lower than for CSF1 IL-6 levels (p = 0.0077, and p = 0.0431, respectively). There were no significant differences of the ratio of CSF2/CSF1 IL-6 levels between patients with dexamethasone and those without dexamethasone. CSF2 sTNFR1 levels of patients with dexamethasone were significantly lower than for CSF1 sTNFR1 levels (p = 0.0208). However, CSF2 sTNFR1 levels of patients without dexamethasone were significantly higher than for CSF1 sTNFR1 levels (p = 0.0422). The ratio of CSF2/CSF1 sTNFR1 levels of patients with dexamethasone was significantly lower than that without dexamethasone (p = 0.0063). Our present study suggests that dexamethasone inhibits increase of CSF sTNFR1 levels after antibiotics therapy in bacterial meningitis.

Serum and CSF levels of cytokines in acute encephalopathy following prolonged febrile seizures.

It is well known that an acute encephalopathy occasionally follows prolonged febrile seizures. We measured the concentrations of interferon-gamma, tumor necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), IL-4, IL-6, IL-10, and soluble TNF receptor 1 (sTNFR1) in serum and CSF during the acute stage in 13 children with acute encephalopathy following prolonged febrile seizures (AEPFS) and 23 with prolonged febrile seizures without encephalopathy (PFS) to investigate the pathogenesis of AEPFS. Serum IL-6, IL-10, sTNFR1, and CSF IL-6 levels were significantly higher in AEPFS and PFS compared with control subjects. CSF IL-6 levels in AEPFS were significantly higher than those in PFS, but not serum IL-6, IL-10, or sTNFR1. The CSF IL-6 levels were significantly higher than the serum levels in AEPFS, but not PFS. The serum levels of sTNFR1 and IL-10 were significantly higher than those in the CSF in AEPFS and PFS. The serum IL-10 and sTNFR1 levels in patients who did not experience a second seizure were significantly higher than those in patients who experienced a second seizure, which was characterized by clusters of complex partial seizures several days after the initial prolonged febrile seizure. Our results suggest that serum IL-6, IL-10, TNF-alpha, and CSF IL-6 are part of the regulatory system of cytokines in AEPFS.

[Analysis of 11 patients with profound multiple disabilities who underwent laryngotracheal separation].

We examined the clinical usefulness of laryngotracheal separation surgery for patients with profound multiple disabilities (PMD). The subjects were 11 severely retarded children who experienced repeated incidents of aspiration pneumonia or who were enough to have aspiration pneumonia easily. A retrospective investigation of their medical records was performed regarding pre- and post-operative data, including the number of times sputum suctionings were required, the number of times pneumonia developed, respiratory conditions, and nutrition methods. The guardians were interviewed regarding musle tone, spasm, sleep quality, internal medications, and changes in mood. After surgery, improvement was confirmed in the number of times sputum suctionings were required, the incidence of pneumonia and respiratory conditions, and oral intake of food in three children. The guardians were aware of improvements in their children's sleep quality and mood. Laryngotracheal separation surgery can reduce the burden of health care for patients with PMD by improving their respiratory conditions and methods of nutrition intake.

Matrix metalloproteinase-9 and tissue inhibitors of metalloproteinases 1 in influenza-associated encephalopathy.

Matrix metalloproteinase-9 (MMP-9) and tissue inhibitors of metalloproteinases 1 (TIMP-1) play important roles in the function of the blood-brain barrier. Serum MMP-9 and TIMP-1 concentrations were determined in influenza virus infection with or without neurologic complications. Our results suggest that an imbalance between MMP-9 and TIMP-1 damages the blood-brain barrier and promotes febrile seizure or encephalopathy in influenza virus infection.