Titania-containing bioactive bone cement for total hip arthroplasty in dogs.

We developed a composite cement containing low-content bioactive titania fillers dispersed among specific polymethylmethacrylate (PMMA) polymers and investigated the mechanical properties and bioactivity of this titania bone cement (TBC) under load-bearing conditions in cemented total hip arthroplasty (THA) in adult female beagles. TBC and PMMA bone cement (PBC) were compared using custom-made prostheses. The dogs were killed 1, 3, 6, and 12 months postoperatively. The acetabulum was harvested to evaluate the osteoconductivity of the cement, whereas the femur was harvested for the push-out test and histological analyses. The compressive strength of TBC was significantly higher than that of PBC (p < 0.001), whereas the flexural and tensile strengths, as well as fracture toughness, were equivalent. The bonding strength values for TBC and PBC were 72.9 and 58.0 N/mm at 1 month, 69.4 and 57.2 N/mm at 3 months, 106.1 and 85.0 N/mm at 6 months, and 114.3 and 100.7 N/mm at 12 months, respectively. Histologically, TBC was in direct contact with bone without intervening with fibrous tissue over larger areas and newly formed bone was observed along the cement. The excellent mechanical properties and apparent bioactivity of this novel bone cement indicate its potential utility in clinical practice. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1238-1245, 2019.

Surface electromyogram and muscle ultrasonography for detection of muscle fasciculations in pediatric peripheral neuropathy.

A 12-year-old girl presented with talipes equinus of both legs, attenuation of upper and lower limb tendon reflexes, thermal hyperalgesia, and reduction of vibratory sensation. On clinical examination, muscle twitches of fingers of both hands, as well as the abductor halluces and the dorsal interossei muscles of the right foot were observed. Nerve conduction velocity was significantly declined in the upper and lower extremities. Needle electromyography (EMG) was not performed; however, ultrasonography revealed repetitive, semi-regular muscle twitches lasting 0.2-0.4s, concomitant with muscle discharges on surface EMG in the right foot muscles. These findings were compatible with contraction fasciculation in muscles under chronic reinnervation. Nerve and muscle biopsies were suggestive of chronic motor, sensory, and autonomic neuropathy. This is the first case of pediatric peripheral neuropathy where muscle fasciculation was noninvasively identified by simultaneous surface EMG and ultrasonography.

EEG Power Spectrum Analysis in Children with ADHD.

BACKGROUND: Attention deficit disorder/hyperactivity disorder (ADHD) is a pathological condition that is not fully understood. In this study, we investigated electroencephalographic (EEG) power differences between children with ADHD and healthy control children. METHODS: EEGs were recorded as part of routine medical care received by 80 children with ADHD aged 4-15 years at the Department of Pediatric Neurology in Tottori University Hospital. Additionally, we recorded in 59 control children aged 4-15 years after obtaining informed consent. Specifically, awake EEG signals were recorded from each child using the international 10-20 system, and we used ten 3-s epochs on the EEG power spectrum to calculate the powers of individual EEG frequency bands. RESULTS: The powers of different EEG bands were significantly higher in the frontal brain region of those in the ADHD group compared with the control group. In addition, the power of the beta band in the ADHD group was significantly higher in all brain regions, except for the occipital region, compared with control children. With regard to developmental changes, the power of the alpha band in the occipital region showed an age-dependent decrease in both groups, with slightly lower power in the ADHD group. Additionally, the intergroup difference decreased in children aged 11 years or older. As with the alpha band in the occipital region, the beta band in the frontal region showed an age-dependent decrease in both groups. Unlike the alpha band, the power of the beta band was higher in the ADHD group than in the control group for children of all ages. CONCLUSION: The observed intergroup differences in EEG power may provide insight into the brain function of children with ADHD.

Distinguishing Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion from Prolonged Febrile Seizures by Acute Phase EEG Spectrum Analysis.

BACKGROUND: To differentiate the features of electroencephalography (EEG) after status epileptics in febrile children with final diagnosis of either febrile seizure (FS) or acute encephalopathy for an early diagnosis. METHODS: We retrospectively collected data from 68 children who had status epilepticus and for whom EEGs were recorded within 120 h. These included subjects with a final diagnosis of FS (n = 20), epileptic status (ES; n = 11), acute encephalopathy with biphasic seizures and late reduced diffusion (AESD; n = 18), mild encephalopathy with a reversible splenial lesion (MERS; n = 7), other febrile encephalopathies (n = 10), hypoxic-ischemic encephalopathy (n = 1), and intracranial bleeding (n = 1). Initially, all EEGs were visually assessed and graded, and correlation with outcome was explored. Representative EEG epochs were then selected for quantitative analyses. Furthermore, data from AESD (n = 7) and FS (n = 16) patients for whom EEG was recorded within 24 h were also compared. RESULTS: Although milder and most severe grades of EEG correlated with neurological outcome, the outcome of moderate EEG severity group was variable and was not predictable from usual inspection. Frequency band analysis revealed that solid delta power was not significantly different among the five groups (AESD, MERS, FS, ES and control), and that MERS group showed the highest theta band power. The ratios of delta/alpha and (delta + theta)/(alpha + beta) band powers were significantly higher in the AESD group than in other groups. The alpha and beta band powers in EEGs within 24 h from onset were significantly lower in the AESD group. The band powers and their ratios showed earlier improvement towards 24 h in FS than in AESD. CONCLUSION: Sequential EEG recording up to 24 h from onset appeared to be helpful for distinction of AESD from FS before emergence of the second phase of AESD.

Ambroxol chaperone therapy for neuronopathic Gaucher disease: A pilot study.

OBJECTIVE: Gaucher disease (GD) is a lysosomal storage disease characterized by a deficiency of glucocerebrosidase. Although enzyme-replacement and substrate-reduction therapies are available, their efficacies in treating the neurological manifestations of GD are negligible. Pharmacological chaperone therapy is hypothesized to offer a new strategy for treating the neurological manifestations of this disease. Specifically, ambroxol, a commonly used expectorant, has been proposed as a candidate pharmacological chaperone. The purpose of this study was to evaluate the safety, tolerability, and neurological efficacy of ambroxol in patients with neuronopathic GD. METHODS: This open-label pilot study included five patients who received high-dose oral ambroxol in combination with enzyme replacement therapy. Safety was assessed by adverse event query, physical examination, electrocardiography, laboratory studies, and drug concentration. Biochemical efficacy was assessed through evidence of glucocerebrosidase activity in the lymphocytes and glucosylsphingosine levels in the cerebrospinal fluid. Neurological efficacy was evaluated using the Unified Myoclonus Rating Scale, Gross Motor Function Measure, Functional Independence Measure, seizure frequency, pupillary light reflex, horizontal saccadic latency, and electrophysiologic studies. RESULTS: High-dose oral ambroxol had good safety and tolerability, significantly increased lymphocyte glucocerebrosidase activity, permeated the blood-brain barrier, and decreased glucosylsphingosine levels in the cerebrospinal fluid. Myoclonus, seizures, and pupillary light reflex dysfunction markedly improved in all patients. Relief from myoclonus led to impressive recovery of gross motor function in two patients, allowing them to walk again. INTERPRETATION: Pharmacological chaperone therapy with high-dose oral ambroxol shows promise in treating neuronopathic GD, necessitating further clinical trials.

Sequential neuroradiological and neurophysiological studies in a Japanese girl with merosin-deficient congenital muscular dystrophy.

We describe the early manifestation and sequential assessment of the central and peripheral nervous system in a Japanese girl with merosin-deficient congenital muscular dystrophy. She showed severe hypotonia (''floppy infant") and suffered mild respiratory failure postnatally. Serum creatine kinase was elevated to 11,487 IU/L. The muscle biopsy showed dystrophic changes with negative expression of merosin (laminin α2), thereby confirming merosin-deficient congenital muscular dystrophy. Her motor milestones were severely delayed, but she could sit without support at the age of 3 years. After 3 years, her motor ability deteriorated and by the age of 5 years, she could not sit and control her neck. Magnetic resonance imaging (MRI) at 2 months of age revealed patterns that were appropriate for her age. At 1 year of age, the T2 weighted images showed diffuse high signal intensities throughout the centrum semiovale, and periventricular and subcortical white matter of the frontal and occipital lobes, while the U fibers, the corpus callosum and the internal capsule were spared. At the age of 7 years, these white matter abnormalities decreased. MR spectroscopy (MRS) revealed normal values of N-acetylaspartate (NAA)/creatine (Cr) and choline (Cho)/Cr metabolite ratios as well as slightly increased myoinositol (mI)/Cr metabolite ratios. Neurophysiological motor nerve conduction velocity (MCV) and compound muscle action potential (CMAP) of the median nerve were in the normal range at the age of 2 months. After the child reached 1 year of age, the MCV and CMAP lagged behind those of healthy controlled children. The sensory nerve conduction velocity of the median nerve demonstrated a mild delay at the age of 15 months. It improved to normal range at the age of 6 years but decreased at 7 years of age. These sequential findings suggest not only that muscular degeneration and dysmyelination had occurred but also that various other factors, including demyelination and the vasogenic system, may influence the pathology of MDC1A.

[Real-time tissue elastography in chronic liver disease].

BACKGROUND/AIM: In patients with chronic liver diseases, the histological classification of liver fibrosis is essential for predicting prognosis and selecting appropriate antiviral therapy. This study aimed to determine the usefulness of a new noninvasive method for the assessment of liver fibrosis by using real-time tissue elastography, which can be performed with conventional ultrasound probes. METHODS: Thirty-nine patients who had liver fibrosis and had undergone liver resection or liver biopsy were included in this study. The surgical specimens obtained were examined to determine the histological stage of liver fibrosis. The strain ratio of subcutaneous fat tissue to liver tissue was calculated. We examined the correlation between the strain ratio and the histological liver fibrosis stage, and compared the utility with various surrogate liver fibrosis markers. RESULTS: The strain ratio significantly differed with the stage of liver fibrosis, and they had significant correlation (Kruskal-Wallis test: p<0.0001; Spearman's rank correlation, p<0.0001, r=0.797). We identified 5.8 and 3.7 as the cutoff values of strain ratio for the diagnosis of cirrhosis and significant fibrosis. The sensitivity at these values was 92.9% and 81.9% respectively; the specificity, 96.0% and 88.9%; and the areas under the receiver operating characteristic curve (AUROCs), 0.977 and 0.913, respectively. The AUROC was superior to the other surrogate liver fibrosis markers tested. CONCLUSIONS: Real-time tissue elastography is a useful method for the diagnosis of significant fibrosis and cirrhosis in patients with chronic liver diseases.

[Study of autonomic dysfunction in patients with obstructive sleep apnea syndrome to head-up tilt test].

Although it is well known that autonomic dysfunction in obstructive sleep apnea syndrome (OSAS) is associated with hypertension, its relationship to hypotension and orthostatic dysregulation is still unclear. We examined the response of blood pressure (BP) and cardiovascular autonomic function to head-up tilt (HUT) test in patients with OSAS. In this study, 14 patients(mean age: 65+/-2 years old, male/female: 11/3) with diagnosed OSAS by overnight polysomnography and 84 healthy subjects(mean age: 62+/-1 years old, male/female: 46/38) underwent HUT test(from 5 to 10 min at 45 degrees). Autonomic functions were evaluated by spectrum analysis of blood pressure and heart rate variability. In healthy subjects, systolic BP was unchanged by HUT test due to the enhancement of sympathetic nerve activity and the inhibition of parasympathetic nerve activity. In contrast, autonomic responses were unchanged and systolic BP tended to be decreased by HUT test in OSAS patients. In conclusion, the results of this study suggest that baroreflex function is impaired in patients with OSAS. Furthermore, HUT test with spectrum analysis may be useful to evaluate autonomic functions in OSAS patients.

Low signal intensity and increased anisotropy on magnetic resonance imaging in the white matter lesion after head trauma: unrecognized findings of diffuse axonal injury.

We report on a four-year-old girl with head trauma caused by a motor vehicle accident. She presented with delirium, oculomotor palsy and ptosis in her left eye, left hemiparesis, and pyramidal signs in all extremities. Computed tomography on the day of admission showed diffuse cerebral edema with right-sided predominance. Magnetic resonance images on day 3 of admission showed lesions of diffuse axonal injury and contusion in the corpus callosum and right occipital and bilateral temporal lobes. There was a low-intensity lesion in the white matter of the right hemisphere on T2-weighted images, fluid-attenuated inversion recovery, T2()-weighted images, apparent diffusion coefficient maps and diffusion-weighted images. This low-intensity lesion disappeared by day 7, and a transient brain atrophy in the right hemisphere appeared on day 28. The low signal intensity in the cerebral white matter was apparently different from that associated with contusion and typical diffuse axonal injury, and might represent a late-onset accumulation of non-heme iron and free radicals in the white matter after head trauma.

Lower brainstem dysfunction in an infant with persistent primitive trigeminal artery.

A 6-month-old boy with persistent primitive trigeminal artery (PPTA) presented with stridor, dysphagia, delayed motor development and postural neck and shoulder dystonia. Magnetic resonance imaging/angiography and ultrasonography revealed PPTA, with flow from the dilated basilar artery to the right internal carotid artery, lower brainstem compression by the dilated basilar artery, and cerebellar vermis hypoplasia. Evoked potentials showed lower pons and medulla oblongata functional disruption. These lesions may be related to vascular etiology in the lower brainstem or to congenital malformation syndrome involving infratentorial structures. The relationship of this condition to Möbius syndrome is discussed.

Disappearance of frontal N30 component of median nerve stimulated SSEPs in two young children with abnormal striatal lesions.

Median nerve stimulated short-latency somatosensory evoked potentials (MN-SSEPs) were performed in two young children with extrapyramidal symptoms. Brain MRI showed bilaterally symmetric striatal lesions in both cases. The subcortical components (N9, N11, N13, N18, P11, and P13) and the parietal component (N20) were normally detected, whereas the frontal component (N30) was not detected bilaterally in either case. In conclusion, our findings suggest that frontal N30 disappearance could be observed since as early as young childhood and it may pathophysiologically reflect severe dysfunction in the extrapyramidal system.

Topographic MN-SSEPs (N18, N20 and N30) might characterize underlying CNS involvements in representative types of cerebral palsy.

This study is aimed at constructing the neurophysiological basis for determining the characteristic features of cerebral motor disturbance in representative cerebral palsy (CP) types using topographical S-SEPs technology. Median-nerve stimulated S-SEPs (MN-SSEPs) were examined for 23 patients with four representative types of cerebral palsy: 6 athetotic (including 3 patients due to hypoxic-ischemic encephalopathy (HIE) and 3 to kernicterus), 7 hemiplegic, 5 diplegic and 5 tetraplegic types, and 13 normal controls. In HIE group of athetotic CP, frontal N30 specifically showed severe amplitude reduction or abolishment. In hemiplegic CP, both N20 and N30 on the affected cerebral side tended either to disappear or to be normally evoked at the same time, and their mean amplitudes declined severely. In diplegic CP, the amplitudes of subcortical N18 and parietal N20 were not small but significantly enlarged. N30 amplitude stayed within normal. The reason for this unexpected enlargement of N18 and N20 is unclear, but may be partly due to premature birth which caused abnormally abundant dendritic spine due to absence from perinatal normal spine elimination in the brainstem. In several quadriplegic patients, both N20 and N30 disappeared. The mean amplitude of N30 severely decreased. In conclusion, topographical results of N18, N20 and N30 may basically suggest the underlying involvement of nervous structures in CP according to their representative type.

Re-evaluation of short latency somatosensory evoked potentials (P13, P14 and N18) for brainstem function in children who once suffered from deep coma.

One of the major clinical features of brain death is deep coma. Therefore, we re-evaluated retrospectively electrophysiological examinations of brainstem function in about 31 children who had once suffered from deep coma in order to reveal its pathophysiological characteristics. The patient age at coma ranged from 1 month to 10 years (mean 2 years 1 month). The electrophysiological examinations were performed, including any of short-latency somatosensory evoked potential (SSEP), brainstem auditory evoked potential (BAEP) and blink reflexes. We first compared results between the fair and poor prognostic groups, and then re-evaluated SSEP results on a few severely impaired patients with persistent vegetative state (PVS). Subsequently, SSEP clarified more specific findings for a deep coma condition than BAEP and blink reflex. A lack of P14, N18 and N20, and an amplitude reduction or vagueness of P13 in SSEP in these children strongly suggested high risk in their future neurological prognosis. In conclusion, electrophysiological examinations, especially SSEP (P13, P14 and N18), might be very useful in obtaining a long-term neurological prognosis after deep coma in children.

Congenital mirror movement: a study of functional MRI and transcranial magnetic stimulation.

Two male patients (a child and an adult) with congenital mirror movement were studied using functional MRI (fMRI) and transcranial magnetic stimulation (TMS). Bilateral primary sensorimotor cortices were activated during unilateral hand gripping on fMRI when the child patient was 8 years old andthe adult was 37 years old. Bilateral motor evoked potentials were induced from the hand and forearm muscles after TMS of each hemisphere. Bilateral motor responses were also induced from the arm muscles in the adult patient. Bilateral motor responses had short and similar latencies. Contralateral motor responses to TMS were smaller than ipsilateral ones in the hand muscles, while contralateral responses were larger than ipsilateral ones in the arm muscles. Contralateral hand motor responses reduced in amplitude or disappeared with increasing age while in the child patient, mirror movements decreased gradually. Our results suggest that bilateral activation of the primary sensorimotor cortices during intended unilateral hand movement and bilateral motor responses to TMS account, at least in part, for the pathophysiology of congenital mirror movement. Reduction of contralateral hand motor responses may be related to the decrease in mirror movements during development.

[P22 and N30 of median nerve SSEPs--independence of the frontal waves from parietal waves].

Median nerve short-latency somatosensory evoked potentials (MN-SSEPs) were recorded from the scalp to assess frontal lobe functions in children. Forty-nine patients, aged between three and fifty years old underwent 87 examinations. They were divided into four groups: A (3 to 4 years old); B (5 to 6 years old); C (7 to 15 years old) and D (20 to 50 years old). Stimulus electrodes were placed near the wrist on the median nerve. The study was done mostly in the waking state. To evaluate the independence of the frontal lobe from the parietal lobe we correlated the frontal P22 and parietal N20, and compared the frontal N30 with parietal negative waves. The intervals of the peak latency differed between P22 and N20 by -1.5 to 1.5 msec. Significant differences were noted between groups A and D, and between C and D. N30 and negative parietal waves resembled each other in children 3 to 4 years of age, but became different from 5 years old. They were dissimilar after 6 years old. Therefore, N30 waves were useful for evaluating the frontal elements in children over 5 years of age.