[Issues of transition support to adulthood and the practices of pediatric-adult healthcare transition in neurological diseases].

A workshop of the Special Committee on Measures for Transition from Pediatric to Adult Health Care, the Japanese Society of Neurology was held to discuss various issues and practices involved in healthcare transition. The following points were addressed: (1) the history of, and issues involved in, promoting support for patients requiring medical care, (2) cooperation between pediatric medical centers and university hospitals, (3) collaboration between pediatrics and neurology in medical and rehabilitation facilities, and (4) a questionnaire survey of members of the Japanese Society of Neurology. The reasons for extreme difficulties in pediatric-adult healthcare transition for patients with neurological diseases, especially those who require continuous intensive medical care over a long period of time, include the difference in the operating systems of pediatric and adult departments, in addition to the difference in the diseases treated during childhood and adulthood. For holistic transition support, it is necessary to strengthen cooperation not only among medical professionals, but also among multiple professions, as well as between local communities and government.

Foot extension and retraction in the clam Calyptogena okutanii without any Keber's valve: an inflatable fastener bag model.

In order to investigate the foot manipulation of a clam without a Keber's valve, Calyptogena okutanii was examined by light microscopy, magnetic resonance imaging and computed tomography. The foot chamber was divided into two compartments by a dense muscle fastener zone (FZ) comprising a pedal artery and sinuses in the mid-sagittal plane in between muscles running in the anterior-posterior oblique direction. The distal part of the foot chamber (inflatable fastener bag, IFB) had a loose superficial muscle layer. The proximal part of the foot chamber (visceral reservoir, VR) was covered by a dense superficial muscle layer. The outlet of the VR was connected with the hinge ligament duct, consisting of the hinge ligament, a pair of shells and the pericardium. Based on these anatomical structures, foot extension starts from contraction of muscles in the FZ, so that flow in the FZ is stopped. Then, the superficial muscles of the foot contract, and the pressure of the IFB increases so that the foot can extend. Foot retraction starts from the relaxation of muscles in the FZ so that the hemolymph returns to the VR. The hinge ligament duct allows a constant return flow from the foot chamber to the gills and the heart. The heart rate and the flow in the FZ, which decreased and increased during the foot extension and retraction, respectively, supported this model. In conclusion, the FZ of Calyptogena okutanii could be an alternative to Keber's valve in Anodonta, playing a similar role.

An autopsied case report of spastic paraplegia with thin corpus callosum carrying a novel mutation in the SPG11 gene: widespread degeneration with eosinophilic inclusions.

BACKGROUND: The detailed neuropathological features of patients with autosomal recessive hereditary spastic paraplegia with a thin corpus callosum (TCC) and SPG11 mutations are poorly understood, as only a few autopsies have been reported. Herein, we describe the clinicopathological findings of a patient with this disease who received long-term care at our medical facility. CASE PRESENTATION: A Japanese man exhibited a mild developmental delay in early childhood and intellectual disability, followed by the appearance of a spastic gait by age 13. At the age of 25 years, he became bedridden and needed a ventilator. Genetic analysis revealed a homozygous splice site variant in the SPG11 gene (c. 4162-2A > G) after the provision of genetic counselling and acquisition of informed consent from his parents. He died of pneumonia at the age of 44. His brain weighed 967 g and was characterized by a TCC, and his spinal cord was flattened. Microscopically, degeneration was observed in the posterior spinocerebellar tract, the gracile fasciculus, and the posterior column in addition to the corticospinal tract. Marked neuronal loss and gliosis were observed in the anterior horn, Clarke's column, and hypoglossal and facial nuclei. Various types of neurons, in addition to motor neurons, showed coarse eosinophilic granules that were immunoreactive for p62. The loss of pigmented neurons with gliosis was apparent in both the substantia nigra and locus coeruleus. Lateral geniculate body degeneration was a characteristic feature of this patient. Furthermore, peripheral Lewy body-related α-synucleinopathy and scattered α-synuclein-immunoreactive neurites in the locus coeruleus and reticular formation of the brainstem were observed. CONCLUSIONS: In patients with hereditary spastic paraplegia with SPG11 mutations, a variety of clinical phenotypes develop due to widespread lesions containing p62-immunoreactive neuronal cytoplasmic inclusions. We herein report the lateral geniculate body as another degenerative site related to SPG11-related pathologies that should be studied in future investigations.

Detection of muscle activity with forearm pronation exercise using T2-map MRI.

[Purpose] We aimed to detect muscle activity during a forearm pronation exercise using a 0.2 T MRI system. [Participants and Methods] We recruited healthy adult volunteers (7 males, 4 females). Transverse relaxation time (T2) values for 10 forearm muscles were obtained from transverse multiple-spin-echo MR images of one-third of the ulna, lengthwise from the olecranon, in the resting state and after isotonic forearm pronation exercise at three strength levels (5, 15, and 25% of the maximum voluntary contraction). Z values were calculated as (T2e - T2r)/SDr, where T2e, T2r and SDr were T2 after exercise, 34 ms, and 3 ms, respectively. A Z value of 2.56 was used as the threshold for defining muscle activation. [Results] T2 values increased significantly in the pronator teres muscle (agonist), while those in the supinator muscle (antagonist) showed no change. The sensitivity and specificity values obtained were high and low, respectively, for all of the three exercise strength levels employed. In some of the participants, activity was detected in the flexor carpi radialis, extensor carpi ulnaris, and extensor digitorum. [Conclusion] Using T2-map MRI, we detected activity in primary and secondary mover muscles. We also found individual variations in the use of forearm muscles during pronation.

Rat mandibular condyle and fossa grew separately then unified as a single joint at 20 days old, which was the weaning age.

Magnetic resonance imaging (MRI) was used to observe growth of the mandibular condyle, mandibular fossa, and articular disc as a single unit. Changes in each component's relative position and size were observed using 7-tesla MRI. Mandibular condyle chondrocytes' growth was evaluated with immunohistochemistry, using the expression of zinc transporter ZIP13. Three-dimensional T1-weighted (T1w) MRI was used to obtain images of the TMJ of Sprague Dawley rats at 4-78 days old (P4-78) with a voxel resolution of 65 µm. Two-dimensional T1w MR images were acquired after a subcutaneous injection of the contrast reagent gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA). The T1w MR images showed that the mandibular condyle was located posterior to the mandibular fossa until P20; however, it then moved to a location underneath the mandibular fossa. In the Gd-DTPA enhanced images, the articular disc was identified as a region with lower signal intensity from P20. The number of ZIP13-positive chondrocytes at P6 was larger than the number at P24. In conclusion, the mandibular condyle with cartilage and disc grows on the posterior side of the mandibular fossa until P20, which was the weaning age. Then, the condyle fit into the mandibular fossa and completed the functional unit.

Three novel mutations of the MCT8 (SLC16A2) gene: individual and temporal variations of endocrinological and radiological features.

We performed genetic analysis and clinical investigations for three patients with suspected monocarboxylate transporter 8 (MCT8) deficiency. On genetic analysis of the MCT8(SLC16A2) gene, novel mutations (c.1333C>A; p.R445S, c.587G>A; p.G196E and c.1063_1064insCTACC; p.R355PfsX64) were identified in each of three patients. Although thyroid function tests (TFTs) showed the typical pattern of MCT8 deficiency at the time of genetic diagnosis in all patients, two patients occasionally were euthyroid. A TRH test revealed low response, exaggerated response and normal response of TSH, respectively. Endocrinological studies showed gonadotropin (Gn) deficiency in two adult patients. On ultrasonography, goiter was detected in one patient. Interestingly, pituitary magnetic resonance imaging (MRI) demonstrated atrophy and thinness of the pituitary gland in two patients. Our findings suggest that thyroid status in patients with MCT8 deficiency varies with time of examination, and repeated TFTs are necessary for patients suspected of MCT8 deficiency before genetic analysis. In addition, it is noteworthy that some variations were observed on the TRH test and ultrasonography of the thyroid gland in the present study. Morphological abnormality of the pituitary gland may be found in some patients, while Gn deficiency should be considered as one of the complications.

[Safety and efficacy of surgical closure of the larynx for recurrent aspiration pneumonia in persons with severe motor and intellectual disabilities: a comparative study with tracheoesophageal diversion].

OBJECTIVE: We retrospectively investigated the efficacy and complications of surgical closure of the larynx (SCL) for recurrent aspiration pneumonia in comparison with tracheoesophageal diversion. METHODS: The subjects were persons with severe motor and intellectual disabilities (SMID) who had undergone surgery for recurrent aspiration pneumonia between 1994 and 2011: A 8 SCL patients group and a 16 tracheoesophageal diversion patients group. We investigated two groups the lower respiratory infection incidence, length of hospital stay for the surgery, postoperative complications, and rate of cannula withdrawal, by reviewing medical records. RESULTS: Both the SCL and the tracheoesophageal diversion group showed a reduction in the incidence of infection after surgery, indicating that the efficacy of SCL was equivalent to that of tracheoesophageal diversion in preventing aspiration pneumonea. The SCL group showed a reduction in the length of hospital stay and an increased rate of cannula withdrawal as compared with the tracheoesophageal diversion group. CONCLUSION: The efficacy of SCL was equivalent to that of tracheoesophageal diversion in preventing aspiration for SMID. We consider SLC to have potential for reducing the burden on patients.

Changes to Muscle T2after Single-finger Exercise Measured with 0.2T MR Imaging.

We constructed an arm holder for muscle exercise from a forearm-shaped plastic shell and magnetic resonance (MR) imaging position markers and determined the echo time (39 ms) for T2-weighted spin-echo MR imaging from T2values of the exercised (50 ms) and resting (32 ms) muscle at 0.2 tesla. The smallest detectable muscle was the extensor digiti minimi muscle (cross-sectional area 25 mm²). This combination could be useful to monitor finger exercise in patients undergoing physical therapy.

Real-time PCR assays for monitoring anaerobic fungal biomass and population size in the rumen.

The relationship between copy numbers of internal transcribed spacer 1 (ITS1) and biomass or zoospore count of anaerobic fungi was studied to develop a quantitative real-time PCR-based monitoring method for fungal biomass or population in the rumen. Nine fungal strains were used to determine the relationship between ITS1 copy number and fungal biomass. Rumen fluid from three sheep and a cow were used to determine the relationship between ITS1 copy number and fungal population. ITS1 copy number was determined by real-time PCR with a specific primer set for anaerobic fungi. Freeze-dried fungal cells were weighed for fungal biomass. Zoospore counts were determined by the roll-tube method. A positive correlation was observed between both ITS1 copy number and dry weight and ITS1 copy number and zoospore counts, suggesting that the use of ITS1 copy numbers is effective for estimating fungal biomass and population density. On the basis of ITS1 copy numbers, fluctuations in the fungal population in sheep rumen showed that although the values varied among individual animals, the fungal population tended to decrease after feeding. In the present study, a culture-independent method was established that will provide a powerful tool for understanding the ecology of anaerobic fungi in the rumen.

Intravenous lidocaine for status epilepticus during childhood.

The clinical efficacy of lidocaine for convulsive status epilepticus in 53 convulsive episodes was examined in 37 children (17 males, 20 females). Mean age of patients receiving lidocaine was 3 years 7 months (SD 3y 5mo). Lidocaine administration achieved control of status epilepticus in 19 of 53 convulsive episodes (35.8%). Seizures ceased within 5 minutes of lidocaine administration in all 19 patients who were responsive to the drug. Regarding aetiology of status epilepticus and types of seizures, there was no statistical difference in effectiveness. Mild decrease of oxygen saturation, monitored by pulse oximetry, was observed in one patient, which improved by oxygenation using a mask. Lidocaine is a useful anticonvulsive agent; however, the response rate to lidocaine appears to be quite low, as less than half of the seizures were effectively controlled by lidocaine. Favourable properties of the drug include prompt responses, less alteration of consciousness, and fewer adverse effects, including less respiratory depression.

[Choice and administration sequence of antiepileptic agents for status epilepticus and frequent seizures in children].

We investigated the sequence of the administration, the efficacy and the safety of antiepileptic drugs (AED) given intravenously for the treatment of status epilepticus and frequent seizures in children. Our institute has a recommended sequence of AED administration for treatment of status epilepticus: the first-line agent is diazepam (0.3 - 0.5 mg/kg administered intravenously, once or twice). The second-line drugs include midazolam (0.15 - 0.4 mg/kg intravenously, once or twice, and if necessary, followed by continuous infusion at 0.06 - 0.18 mg/kg/hour), lidocaine (1 - 2 mg/kg intravenously, once or twice, and if necessary, followed by continuous infusion at 2 - 4 mg/kg/hour) and phenytoin (10 - 20 mg/kg, infused slowly). For those patients who previously experienced a seizure which was refractory to diazepam but responsive to the second-line agent, it was recommended to use the second-line agent as a first-line agent. When seizures were refractory to the first and second-line agents, thiopental was administered (3 - 10 mg/kg intravenously, and if necessary, followed by continuous infusion at 2 -5 mg/kg/hour). The etiologies of 177 occasions of status epilepticus and frequent seizures were categorized into two groups:epilepsy (n = 95) and situation-related seizures (n = 82). Situation-related seizures included febrile seizures (n = 44), acute encephalopathy/encephalitis (n = 31) and benign infantile convulsions (n = 7). The ages of the patients ranged from 0.1 to 18.4 years (average +/- SD:3.69 +/- 3.15 years). Diazepam was administered as the first-line drug on 157 of 177 occasions (88.7%). On 116 occasions the second-line agents were administered. Midazolam and lidocaine were injected as the second-line agent on 54 (46.6%), and on 33 (28.4%) occasions, respectively, although both midazolam and lidocaine injections were off-label use for seizure control in Japan. Thiopental was used as the third to fifth-line agent. Effective ratios (effective occasions/total occasions) of each drug were the following: thiopental 19/21 (90.4%), midazolam 57/99 (57.6%), lidocaine 25/60 (41.7%), phenytoin 16/41 (39.0%), diazepam 59/164 (36.0%). Thiopental was statistically more effective than midazolam, lidocaine, diazepam or phenytoin (p < 0.01), and midazolam was statistically more effective than diazepam (p < 0.01) or phenytoin (p < 0.05). Administration of thiopental caused complications more frequently than the other agents (p < 0.01): The complications by thiopental were severe in some cases requiring intratracheal intubations and artificial ventilation. From the viewpoint of both efficacy and safety, midazolam should be recommended as one of the first-line agents for status epilepticus.

[Single photon emission computed tomography findings in a case of alternating hemiplegia of childhood in relation to migraine].

Single photon emission computed tomography (SPECT) was performed 3 times during attacks and performed 4 times during postictal periods on a case of alternating hemiplegia of childhood. Hyperperfusion of the corresponding hemisphere to hemiparesis was suggested by asymmetric increase RI uptake during the ictal scans, whereas interictal scans showed symmetric topography of cerebral blood flow. Manifestations except hemiplegia included loss of consciousness and vomiting. These manifestations and ictal SPECT findings are the same evidence as hemiplegic migraine. It suggests that these two disorders have a similar pathophysiology. There are two interesting findings regarding this patient. The first finding is magnetic resonance imaging showed progressive cerebellar atrophy. Second finding is interictal SPECT showed a progressive decrease of cerebral perfusion, especially in cerebellar hemispheres. These two findings suggest alternating hemiplegia of childhood may be a chronic progressive disorder.