De novo EEF1A2 mutations in patients with characteristic facial features, intellectual disability, autistic behaviors and epilepsy.

Eukaryotic elongation factor 1, alpha-2 (eEF1A2) protein is involved in protein synthesis, suppression of apoptosis, and regulation of actin function and cytoskeletal structure. EEF1A2 gene is highly expressed in the central nervous system and Eef1a2 knockout mice show the neuronal degeneration. Until now, only one missense mutation (c.208G > A, p.Gly70Ser) in EEF1A2 has been reported in two independent patients with neurological disease. In this report, we described two patients with de novo mutations (c.754G > C, p.Asp252His and c.364G > A, p.Glu122Lys) in EEF1A2 found by whole-exome sequencing. Common clinical features are shared by all four individuals: severe intellectual disability, autistic behavior, absent speech, neonatal hypotonia, epilepsy and progressive microcephaly. Furthermore, the two patients share the similar characteristic facial features including a depressed nasal bridge, tented upper lip, everted lower lip and downturned corners of the mouth. These data strongly indicate that a new recognizable disorder is caused by EEF1A2 mutations.

Clinico-radiological features of subarachnoid hyperintensity on diffusion-weighted images in patients with meningitis.

AIM: To investigate the clinical and radiological features of meningitis with subarachnoid diffusion-weighted imaging (DWI) hyperintensity. MATERIALS AND METHODS: The clinical features, laboratory data, and radiological findings, including the number and distribution of subarachnoid DWI hyperintense lesions and other radiological abnormalities, of 18 patients seen at five institutions were evaluated. RESULTS: The patients consisted of eight males and 10 females, whose ages ranged from 4 months to 82 years (median 65 years). Causative organisms were bacteria in 15 patients, including Haemophilus influenzae, Streptococcus pneumoniae, Streptococcus agalactiae, Staphylococcus aureus, Klebsiella pneumoniae, and Listeria monocytogenes. The remaining three were fungal meningitis caused by Cryptococcus neoformans. Subarachnoid DWI hyperintense lesions were multiple in 16 of the 18 cases (89%) and predominantly distributed around the frontal lobe in 16 of the 18 cases (89%). In addition to subarachnoid abnormality, subdural empyema, cerebral infarction, and intraventricular empyema were found in 50, 39, and 39%, respectively. Compared with paediatric patients, adult patients with bacterial meningitis tended to have poor prognoses (7/10 versus 1/5; p = 0.1). CONCLUSION: Both bacterial and fungal meningitis could cause subarachnoid hyperintensity on DWI, predominantly around the frontal lobe. This finding is often associated with poor prognosis in adult bacterial meningitis.

Clinical and neuroradiologic findings of congenital hydrocephalus in infant born to mother with HTLV-I-associated myelopathy.

We describe clinical and neuroradiologic findings in a male infant with congenital hydrocephalus born to a mother who developed human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy. Ultrasonography at age 20 days showed multiple cysts in the subependymal germinal matrix and enlarged lateral ventricles. Elevation of serum HTLV-I antibody suggested that his hydrocephalus was probably due to intrauterine HTLV-I infection. HTLV-I may cause neurotropic infection in utero.

Multiple epiphyseal dysplasia with small head, congenital nystagmus, hypoplasia of corpus callosum, and leukonychia totalis: a variant of Lowry-Wood syndrome?

We report on a boy with multiple epiphyseal dysplasia (MED), mild short stature, small head, mental retardation and congenital nystagmus associated with other visual problems. These manifestations were similar to those seen in Lowry-Wood syndrome (LWS). He also had hypoplasia of the corpus callosum and leukonychia totalis, which were not described in the previous cases.

Immunostaining of human amniotic epithelial cells: possible use as a transgene carrier in gene therapy for inborn errors of metabolism.

Immunoreactivity of human cultured amniotic epithelial (AE) cells was investigated to evaluate the possible use of these cells as a transgene carrier in gene therapy for inborn errors of metabolism. AE cells were prepared and cultured by the methods described previously. Flow cytometry analysis revealed that these cells did not express any class II antigen at all on their surfaces. But the class I antigen was slightly expressed on their surfaces. Immunoperoxidase staining was slightly positive as to the class I antigen but not to the class II antigen at all. pSV-beta-galactosidase was transfected into AE cells by means of electroporation, followed by staining of the cells with X-gal. Several cells in 60 mm dish expressed beta-galactosidase activity. The possible gene transfer of beta-galactosidase into cultured AE cells may suggest that these cells could be used as a transgene carrier in gene therapy for inborn errors of metabolism.

Evidence for active acetylcholine metabolism in human amniotic epithelial cells: applicable to intracerebral allografting for neurologic disease.

Human amniotic epithelial (HAE) cells have been used for allotransplantation in patients with lysosomal storage disease due to lack of expression of HLA antigens. Previously, we have reported the expression of differentiation markers for both neural stem cells, and neuron and glial cells. In the present study, we investigated the presence of choline acetyltransferase (ChAT) and acetylcholine (ACh) in HAE cells using different experimental approaches. Cultured HAE cells showed strong immunoreactivity against ChAT antibody. ChAT activity in primary cells was 24.9 +/- 8.5 pmol/mg protein/h. Using HPLC with electrochemical detection, ACh was detected in both cell incubation media and cell pellets indicating that these cells synthesize and release ACh in a time-dependent manner. Additional confirmation of this hypothesis was gained from the data obtained from RT-PCR and Western blot analyses which revealed the expression of ChAT mRNA and ChAT protein, respectively, in HAE cells. Results of the present study suggest that HAE cells can possibly be applied for intracerebral allografting to treat neurologic diseases in which cholinergic neurons are damaged.

Early onset muscular dystrophy with autosomal dominant heredity. Report of a family and CT findings of skeletal muscle.

The clinical features and muscle pathology in a female infant and her mother with early onset and slowly progressive muscular dystrophy (MD), possibly transmitted through autosomal dominant inheritance, are described. The mother exhibited multiple joint contractures at birth. The daughter had mild proximal muscle weakness at 2 3/12 years old. The muscle biopsy specimens from both patients showed myopathic changes with evidence of fiber necrosis and regeneration. Computed tomographic (CT) findings of their skeletal muscles suggested that proximal muscles were involved at an early stage, with later gradual involvement of generalized muscles, without a characteristic selectivity pattern in thigh muscles. This may possibly be a clinically benign and distinct variant of MD with a slowly degenerating pattern of skeletal muscles on CT.

Event-related potentials (P300) and EEG activity in childhood partial epilepsy.

To clarify the relationship between the cognitive function and EEG activity, auditory event-related potentials (P300) were examined in 72 patients with partial epilepsy. Twenty-six patients (67 trials) had idiopathic partial epilepsies (IPE), and 46 (118 trials) symptomatic or cryptogenic partial epilepsies (SPE). For this study, patients undergoing carbamazepine monotherapy with a dose of less than 16 mg/kg/day were selected to rule out the effects of anti-epileptic drugs. The results were as follows: (1) The P300 latency tended to be prolonged in association with the EEG slowing in both epileptic groups. (2) There was no clear relationship between the frequency of paroxysmal discharges and the P300 latency. (3) The P300 latency was slightly prolonged in the patients with temporal foci compared with that in ones with extra-temporal foci. (4) There was no significant relationship between the generalization of focal paroxysmal discharges and the P300 latency. These results suggested that the influence of EEG abnormalities (particularly paroxysmal discharges) on the P300 latency is relatively little, and the cognitive dysfunction in partial epilepsies mainly originates from other factors such as the epileptogenic lesion itself.

Epileptic seizures and event-related potentials (P300) in childhood partial epilepsies.

To clarify the relationship between cognitive function and clinical seizures, auditory event-related potentials (P300) were examined in 72 patients (185 trials) with partial epilepsy. Twenty-six patients (67 trials) had idiopathic partial epilepsies (IPE), and 46 (118 trials) symptomatic or cryptogenic partial epilepsies (SPE). In this study, to rule out the effects of epileptogenesis and other factors, we only examined patients with partial epilepsies undergoing carbamazepine (CBZ) monotherapy at doses of less than 16 mg/kg/day. The results were: 1) the mean age-corrected P300 latency in the patients with SPE (394 +/- 38 msec) was significantly prolonged compared with that in the patients with IPE (378 +/- 28). 2) The prolongation of the P300 latency had no relationship to the seizure frequency, seizure type or seizure duration. 3) In both epileptic groups, there was no significant correlation between the seizure-free period and the age-corrected P300 latency. Our results suggest that the effect of clinical seizures on the cognitive function may be relatively little, and that the cognitive dysfunction in partial epilepsies may mainly originate from epileptogenesis or other factors.

Simple and low-cost tele-nuclear medicine conference system with the e-mail protocol.

PURPOSE: Because of the recent innovative growth in computer technology, digital imaging, and the Internet, we can take advantage of these facilities for education and clinical work in nuclear medicine. We developed a tele-nuclear medicine conference system with electronic mail (e-mail) on the Internet. METHODS: Twenty-one physicians (20 radiologists, 1 neurologist), 6 technologists and 2 medical students in six university hospitals (Japan 5, Canada 1), 5 local hospitals in Japan participated in this project. We used digital still cameras (330 k pixels) equipped with a floppy disk drive and 10 x optical zoom to digitize images with JPEG compression (640 x 480 matrix). The images were attached to e-mail messages (containing a brief description of each case). The mail was sent simultaneously to all members on the mailing list. Scintigram and SPECT images as well as other radiological images were sent by e-mail. Reply mails about each case were sent to all members via the mailing list. RESULTS: During a period of 6 months, 18 cases (tumor/infection: 7, bone: 6, cardiovascular: 1, neurology; 3, endocrine: 1) with 144 e-mails (average 5.6/case) were submitted to the conference. The average period of discussion was 15.6 days. The number of attached images was 1 to 9 (average, 4.2/e-mails). JPEG compression rate was 1/10 to 1/20. The quality of the images was good enough for discussion. Some cases required additional images for further discussion. CONCLUSION: Our tele-nuclear medicine conference with an electronic mailing list and digital camera was simple and low-cost. The conference system was useful for education and clinical work.

FDG-PET findings in sclerosing hemangioma of the lung: a case report.

We report a case of sclerosing hemangioma of the lung that showed an intermediately increased accumulation of 18F-fluorodeoxyglucose (FDG) on positron emission tomography (PET). We suggest that FDG-PET may be useful for considering a lesion as benign or low-grade malignant.

Germinoma arising in the basal ganglia in early stage: CT and MR findings.

We report a patient with a germinoma originating in the left basal ganglia. Unenhanced computed tomography (CT) revealed a relatively well-defined high-density lesion, which was slightly enhanced with contrast medium. No tumor stain was noted on angiography. The mass showed hypointensity on T1-weighted magnetic resonance imaging (MRI), and heterogeneous hyperintensity on T2-weighted imaging. The lesion was homogeneously enhanced after the administration of Gd-DTPA. To our knowledge, the MR findings of basal ganglia germinoma have been retrospectively reviewed in just four reported cases, only two of which were examined with Gd-DTPA enhancement. The two cases revealed relatively large masses with cysts and peritumoral edema, and were slightly enhanced after the intravenous injection of Gd-DTPA. Our case was thought to be in the early stage, and its CT and MR findings were slightly different from those of previously reported cases.

Intracaval invasion of left adrenal cortical carcinoma extending into the right atrium.

A case of adrenal carcinoma with advanced inferior vena cava (IVC) involvement is reported. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a large mass over the upper pole of the left kidney, with tumor thrombus from the IVC to the right atrium of the heart. Angiography demonstrated that this mass received its blood supply mainly from the left superior adrenal artery, and, parasitically, the left middle adrenal artery, splenic artery, and lumbar arteries. Venacavography revealed obstruction of the IVC and the collateral, dilated azygos vein. Radical surgery was performed, including resection of the tumor and the tumor thrombus in the IVC and right atrium with the aid of cardiopulmonary bypass. Although renal carcinoma with tumor thrombus invasion of the IVC or atrium is common, adrenal tumor thrombus invasive to the atrium is very rare.

Are animal models useful for understanding the pathophysiology of lysosomal storage disease?

UNLABELLED: Spontaneously occurring genetic lysosomal storage diseases are as rare in other mammalian species as in man. However, the advent of gene targeting technology has revolutionized the state of animal models of genetic diseases. Nearly all lysosomal storage diseases known in man have been duplicated in the mouse. The technology now allows, not only complete inactivation of endogenous genes, but also the introduction of essentially any type of mutation. These animal models can overcome many of the limitations inherent in studies of human patients--rarity of the disease, extremely complex genetic background and logistical and ethical constraints in the design and execution of experiments with human subjects. For example, genetic manipulations of germ cells or cross-breeding experiments between two mutants are readily feasible with animal models. Two major areas of the utility of animal models are the clarification of the pathophysiology/pathogenetic mechanism of disease and the exploration of therapeutic approaches. Examples of experiments using animal models of lysosomal storage disease are presented, primarily from studies undertaken in our own laboratory. CONCLUSION: Animal models have proved invaluable in extending our knowledge of the lysosomal storage diseases and exploring potential therapies.

[Evaluation of cerebral perfusion imaging with N-isopropyl-p-[123I]iodoamphetamine (IMP) in the cases of antiphospholipid syndrome].

Five cases of antiphospholipid syndrome with mild headache, but without any neurological deficits and abnormal findings by CT and MRI, were examined by cerebral blood perfusion SPECT using N-isopropyl-p-[123I]iodoamphetamine (IMP). Although three cases were performed quantification of cerebral blood flow with a microsphere method simultaneously, their values were within normal limits. Two of them showed focal low perfusion areas. One case had relatively low perfusion areas in the bilateral occipital lobes and the right temporal lobe, which improved after treatment. One of two had low perfusion in the bilateral occipital lobes. Other three cases only showed uniformity of radioisotope uptake on the cerebral blood perfusion SPECT. Low perfusion areas in antiphospholipid syndrome might be caused by microarterial thrombosis, microvenous thrombosis or spasms, although they could be reversible. As early detection of cerebral abnormality admit to protect irreversible progress of cerebral blood flow, cerebral blood flow SPECT should be performed in cases of antiphospholipid syndrome with neurological complaints.

[Automatic calculation of left ventricular volume and ejection fraction from gated myocardial perfusion SPECT--basic evaluation using phantom].

We evaluated accuracy of Quantitative Gated SPECT Program that enabled calculation of the left ventricular (LV) volume and ejection fraction by automatically tracing the contour of the cardiac surface. Cardiac phantoms filled with 99mTc-solution were used. Data acquisition was made by 180-degree projection in L type and 360-degree projection in opposed type. Automatic calculation could be done in all processes, which required 3-4 minutes. Reproducibility was sufficient. The adequate cut off value of a prefilter was 0.45. At this value LV volume was 93% of the actual volume in L type acquisition and 95.9% in opposed type acquisition. The LV volume obtained in L type was smaller than that obtained in opposed type (p < 0.05). The tracing of the defects was fair, on the cardiac phantoms with all of 90-degree defects and 180-degree defects of the septal and lateral wall. The LV volume was estimated to be larger on the phantom with 180-degree defect of the anterior wall, and to be smaller on the phantom of 180-degree defect of the inferoposterior wall. Because tracing was deviated anteriorly at the defects. In the patients with similar conditions to 180-degree defect of the anterior wall or inferoposterior wall, the LV volume should be carefully evaluated.

[Relationship between electroencephalographic abnormality and late blink reflex responses in infantile spasms and EIEE].

Electrically elicited blink reflex (BR) were analyzed in seven patients with age dependent epileptic encephalopathies (5 patients with infantile spasms and 2 with EIEE). Four patients with infantile spasms showed prolonged latency of the late BR responses (R2). In 2 patients with EIEE showing suppression burst pattern on EEG, R2 was not detectable. R2 abnormality in BR might reflect the dysfunction of the brainstem reticular formation in age dependent epileptic encephalopathies.

[A case of early-onset and slowly progressive chronic inflammatory demyelinating polyneuropathy--electrophysiological findings with clinical course].

A case of early-onset and slowly progressive chronic inflammatory demyelinating polyneuropathy (CIDP) was reported. Her progressive gait disturbance began at six years of age and she developed pes cavus. At the age of 13 years, a diagnosis of CIDP was made, and oral corticosteroid therapy was started. This therapy was effective, but the disease relapsed soon. Muscular strength improved after supplementation of an immunosuppressant with oral corticosteroid, following steroid pulse therapy. On peripheral motor conduction study, M waves showed very low amplitudes and remarkably delayed onset-latencies. New units of M wave appeared and amplitudes increased soon after initiation of the corticosteroid therapy because of an improvement of conduction block, and durations of M wave were prolonged. Then, in accordance with shortening of M wave latencies, some dispersed units were synchronized and durations reduced. At relapse, changes of M wave showed an inverse relationship to the changes of M wave with clinical improvement. The electrophysiological findings started improving 1 week after the therapy, while clinical improvement was detected several weeks later. We conclude that the change of M wave was a sensitive marker to evaluate the effect of the therapy in our CIDP case.

[A case of Sanfilippo syndrome type C: long-term clinical course and treatment].

We reported a Japanese girl with the Sanfilippo syndrome type C. She was born to healthy parents married consanguineously. She began to deteriorate and became disoriented at the age of 6 year and 8 month. She also developed sleep problems and dysphagia. Physical examination revealed short stature, slightly coarse facial features, contracture of the PIP joints and hypertrophy of the tonsils. There was neither hepatomegaly nor corneal clouding. Laboratory examination demonstrated an increase in urinary excretion of glycosaminoglycan. Electrophoresis of the urinary glycosaminoglycans indicated that heparan sulfate was the predominant component. Enzymatic assay using her skin fibroblasts demonstrated a complete deficiency of acetyl-CoA: a-glucosaminide N-acetyltransferase activity. Low dose erythromycin alleviated hypertrophy of her tonsils, thereby improving dysphagia.