Usefulness of quantitative susceptibility mapping for the diagnosis of Parkinson disease.

BACKGROUND AND PURPOSE: Quantitative susceptibility mapping allows overcoming several nonlocal restrictions of susceptibility-weighted and phase imaging and enables quantification of magnetic susceptibility. We compared the diagnostic accuracy of quantitative susceptibility mapping and R2* (1/T2*) mapping to discriminate between patients with Parkinson disease and controls. MATERIALS AND METHODS: For 21 patients with Parkinson disease and 21 age- and sex-matched controls, 2 radiologists measured the quantitative susceptibility mapping values and R2* values in 6 brain structures (the thalamus, putamen, caudate nucleus, pallidum, substantia nigra, and red nucleus). RESULTS: The quantitative susceptibility mapping values and R2* values of the substantia nigra were significantly higher in patients with Parkinson disease (P < .01); measurements in other brain regions did not differ significantly between patients and controls. For the discrimination of patients with Parkinson disease from controls, receiver operating characteristic analysis suggested that the optimal cutoff values for the substantia nigra, based on the Youden Index, were >0.210 for quantitative susceptibility mapping and >28.8 for R2*. The sensitivity, specificity, and accuracy of quantitative susceptibility mapping were 90% (19 of 21), 86% (18 of 21), and 88% (37 of 42), respectively; for R2* mapping, they were 81% (17 of 21), 52% (11 of 21), and 67% (28 of 42). Pair-wise comparisons showed that the areas under the receiver operating characteristic curves were significantly larger for quantitative susceptibility mapping than for R2* mapping (0.91 versus 0.69, P < .05). CONCLUSIONS: Quantitative susceptibility mapping showed higher diagnostic performance than R2* mapping for the discrimination between patients with Parkinson disease and controls.

An adult form of Alexander disease: a novel mutation in glial fibrillary acidic protein.

Glial fibrillary acidic protein (GFAP) mutation has been reported in Alexander disease. We report a patient with the adult form of Alexander disease who shows a novel mutation in GFAP. This case presented with progressive dysarthria, dysphagia and spastic gait on the right side. Brain and spinal cord MRI showed marked atrophy of the medulla oblongata and spinal cord. Abnormal high signal intensities in the ventral medulla oblongata were detected bilaterally. There were no white matter lesions or contrast enhancing lesions. Recently, there have been reports of patients with a juvenile form of Alexander disease presenting with atrophy or signal abnormalities of the medulla or spinal cord. Atrophy of the medulla and spinal cord have specifically been described as suggestive of Alexander disease [1]. Sequence analysis of the GFAP gene of this patient showed a heterozygous c.221T>C mutation, predicting a p.M74T amino acid change. In all patients suspected of Alexander disease on the basis of MRI findings, GFAP analysis is necessary to confirm the diagnosis.

Adult neural stem and progenitor cells modified to secrete GDNF can protect, migrate and integrate after intracerebral transplantation in rats with transient forebrain ischemia.

Adult neural stem and progenitor cells (NSPCs) are important autologous transplantation tools in regenerative medicine, as they can secrete factors that protect the ischemic brain. We investigated whether adult NSPCs genetically modified to secrete more glial cell line-derived neurotrophic factor (GDNF) could protect against transient ischemia in rats. NSPCs were harvested from the subventricular zone of adult Wistar rats and cultured for 3 weeks in the presence of epidermal growth factor. The NSPCs were treated with fibre-mutant Arg-Gly-Asp adenovirus containing the GDNF gene (NSPC-GDNF) or enhanced green fluorescent protein (EGFP) gene (NSPC-EGFP; control group). In one experiment, cultured cells were transplanted into the right ischemic boundary zone of Wistar rat brains. One week later, animals underwent 90 min of intraluminal right middle cerebral artery occlusion followed by magnetic resonance imaging and behavioural tests. The NSPC-GDNF group had higher behavioural scores and lesser infarct volume than did controls at 1, 7 and 28 days postocclusion. In the second experiment, we transplanted NSPCs 3 h after ischemic insult. Compared to controls, rats receiving NSPC-GDNF had decreased infarct volume and better behavioural assessments at 7 days post-transplant. Animals were killed on day 7 and brains were collected for GDNF ELISA and morphological assessment. Compared to controls, more GDNF was secreted, more NSPC-GDNF cells migrated toward the ischemic core and more NSPC-GDNF cells expressed immature neuronal marker. Moreover, the NSPC-GDNF group showed more effective inhibition of microglial invasion and apoptosis. These findings suggest that NSPC-GDNF may be useful in treatment of cerebral ischemia.

High-frequency repetitive transcranial magnetic stimulation improves refractory depression by influencing catecholamine and brain-derived neurotrophic factors.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive and easily tolerated method of altering cortical physiology. To date, numerous open and sham controlled clinical trials have explored the antidepressant potential of rTMS. In the present study, we investigated clinical trials of high-frequency rTMS (20 Hz) for treatment of refractory depression, and also examined the effect of rTMS on plasma levels of catecholamine metabolites and brain-derived neurotropic factor (BDNF). METHODS: Twenty-six depressed inpatients who met the DSM-IV criteria for major depressive disorder and had failed to respond to treatment with at least two antidepressant drugs given at adequate doses (above 150 mg/day in an equivalent dose of imipramine) and durations (at least 4 weeks for each drug) were enrolled in this study. Eleven were males, 15 females. The ages of the subjects ranged from 19 to 78 years old (mean +/- SD = 52.9 +/- 17.8). All patients were administered left prefrontal 20 Hz rTMS at 80 % MT (total 800 pulses a day) over ten daily sessions. The plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) were analyzed by high-performance liquid chromatography. The plasma levels of BDNF were also measured with the sandwich ELISA method. RESULTS: The mean 17-item Hamilton Rating Scale for Depression (Ham-D) score of 20.5 +/- 5.2 before rTMS was significantly decreased to 15.6 +/- 7.3 after rTMS. Nine of 26 patients (35 %) demonstrated some improvement (Ham-D > or = 25 %) by rTMS. The levels of plasma MHPG, but not those of HVA, were significantly reduced after rTMS treatment, and a negative correlation was observed between the change in plasma MHPG levels and the change in scores of agitation. In addition, the plasma levels of BDNF were significantly increased by 23 % in responders and partial responders, but not in nonresponders, after rTMS treatment, and a trend for association was found between the changes in Ham-D scores and changes in plasma BDNF levels in all patients after rTMS treatment. CONCLUSION: These results suggest that rTMS treatment brings about some improvement in refractory depression, especially for symptoms such as agitation, by influencing MHPG and BDNF, which is in accordance with previous reports showing that BDNF was increased by various antidepressants treatments.

Endovascular treatment of basilar tip aneurysms associated with moyamoya disease.

We report the efficacy and safety of endovascular treatment of basilar tip aneurysms (BTA) in five patients with moyamoya disease. The patients underwent intra-aneurysmal embolisation with detachable platinum coils. Three BTA presented with subarachnoid haemorrhage (SAH); the other two were asymptomatic. In four cases, one embolisation procedure produced >95% angiographic obliteration of the aneurysm. In the other patient, 80-90% obliteration was achieved initially, but due to growth of the residual aneurysm, the procedure was repeated 7 months later. Two patients experienced transient oculomotor paresis as a procedure-related complication. Mean follow-up was 43.6+/-34.0 months (range 8-92 months). One patient died of putaminal haemorrhage unrelated to the aneurysm 15 months after embolisation. The other four had no subsequent SAH and survived without sequelae. Endovascular embolisation using detachable platinum coils proved to be a safe and efficient treatment modality for BTA associated with moyamoya disease.

Somatosensory evoked high frequency oscillations recorded from subdural electrodes.

OBJECTIVES: To examine high frequency oscillations (HFOs) of somatosensory evoked potentials (SEPs) recorded directly from subdural electrodes to investigate the relationship between the primary somatosensory cortex and HFOs. METHODS: SEPs were recorded directly from subdural electrodes previously implanted in 3 patients for clinical evaluation prior to surgical treatment of intractable epilepsy. RESULTS: The primary sensory cortex (area 3b) was proposed as the source of somatosensory HFOs, because the distribution of HFOs recorded from the subdural electrodes agreed with the distribution of the N20-P20 components of the somatosensory evoked potential. The somatosensory HFOs showed a strictly somatotopic source arrangement. There was a polarity inversion of the prophase component and also the N20-P20 component of HFOs across the central sulcus. However, the phase was synchronized in the latter part of the HFOs. CONCLUSIONS: We propose that the origins of the early and latter parts of HFOs are different, and that there was a clear somatotopy.

ROC analysis of detection of metastatic pulmonary nodules on digital chest radiographs with temporal subtraction.

RATIONALE AND OBJECTIVES: The authors' purpose was to evaluate the effect of temporal subtraction on digital chest radiographs in the detection of metastatic pulmonary nodules. MATERIALS AND METHODS: The study included 21 cases with metastatic pulmonary nodule and 21 cases without metastatic nodule. Eleven radiologists, including eight residents and three certified radiologists, provided their confidence levels for the presence or absence of pulmonary nodules without and with temporal subtraction. Their performances without and with temporal subtraction were evaluated by means of receiver operating characteristic analysis with both independent and sequential tests. RESULTS: For the independent test, the radiologists' Az (area under the receiver operating characteristic curve) values were 0.871 without and 0.954 with temporal subtraction, compared with 0.882 and 0.955, respectively, for the sequential test. Diagnosis accuracy was significantly improved with the use of temporal subtraction. There was no significant difference in Az values between the independent and sequential tests. CONCLUSION: Temporal subtraction is useful in the detection of metastatic pulmonary nodules, and this technique augments the value of digital chest radiography.

Decreased susceptibility to pentylenetetrazol-induced seizures after low-frequency transcranial magnetic stimulation in rats.

We studied the effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) on seizure susceptibility in rats. rTMS of 1000 pulses at 0.5 Hz led to a prolonged latency for seizure development after an intraperitoneal injection of pentylenetetrazol. The rTMS effectively prevented the development of status epilepticus of pentylenetetrazol-induced convulsions. These findings indicate that low-frequency rTMS affects the neural excitability, in the direction of anticonvulsive, and therefore, suggest the possibility of therapeutic use of rTMS in epilepsy.

Polarization dependence of resonant X-ray emission spectra in early transition metal compounds.

We calculate the polarization dependent spectra of resonant X-ray emission in TiF3, VF3 and Cr2O3, which have one, two and three 3d electron(s) in the ground state, respectively. We study the detailed mechanism of the spectral structures, comparing with a previous result of TiO2. Then we discuss systematically the difference of spectra with the change of the 3d electron number from group theoretical consideration.

In vivo histological changes occurring in hydroxyapatite cranial reconstruction--case report.

Histological changes were observed in a hydroxyapatite plate and hydroxyapatite granules used to repair a craniotomy defect and removed after 2 years and 9 months of use. The hydroxyapatite plates and granules had completely fused to the cranium, with new bone formation on the dural side extending in a three-dimensional matrix along the pores with the Haversian system in the center. New bone formation was less extensive under the artificial dura than under normal dura. This finding suggests that the dura has the ability to promote bone formation. A new vessel was found along the interconnecting pores. The interconnecting pores allow osteoconduction in the hydroxyapatite plate, so new bone formation can progress. Hydroxyapatite has osteoconduction properties and is biocompatible, so gains strength in vivo through new bone formation, and is the ideal material for artificial bones. Factors important to achieving good bone formation after cranial reconstruction surgery include presence of the dura, and pore size approximate to the Haversian system (100-500 microns) and interconnecting pores in the hydroxyapatite plate.

Cerebellar stimulation in acute cerebellar ataxia.

OBJECTIVES: To report follow-up studies of cerebellar stimulation in patients with acute cerebellar ataxia (ACA). METHODS: We studied two patients with ACA. One patient also had decreased deep sensations in the feet due to combined diseases such as diabetic polyneuropathy and lumbosacral radiculopathies. We applied the technique of electrical stimulation over the cerebellum which was reported previously (Ugawa et al., J Physiol 441 (1991a) 57). RESULTS: Conditioning stimulation over the cerebellum did not reduce the size of motor-evoked potentials to test magnetic stimulation of the motor cortex at conditioning-test intervals of 5, 6, and 7 ms in the acute stage in both patients. However, normal suppression was recognized in the recovery stage in both patients. CONCLUSIONS: This technique was useful for follow-up evaluation of cerebellar function in patients with ACA and was also useful for distinguishing cerebellar ataxia from sensory ataxia in a patient with combined diseases.

Paraspinal motor evoked potentials by magnetic stimulation of the motor cortex.

The authors studied five patients with MS and four patients with HTLV-1 associated myelopathy (HAM) to investigate the usefulness of paraspinal motor evoked potentials (MEP) after magnetic stimulation of the motor cortex. In patients with MS, MEP disappeared or onset latencies were delayed below the lesion. In patients with HAM, the onset latencies were prolonged bilaterally. Thus, paraspinal MEP are very useful in detecting spinal cord lesions.

Delayed cerebral radiation necrosis occurring twice at different regions and times in a patient with a metastatic brain tumour.

No case of histopathologically confirmed delayed cerebral radiation necrosis (DCRN) that occurred twice at different regions and times in the same patient has been previously reported. We present a patient with such a rare clinical course and who is surviving long-term (over 13 years) with a history of a distant metastasis of a malignant tumour. To diagnose DCRN preoperatively was very difficult. However, surgical extirpation seemed to be effective for DCRN. The patient is still in a good performance status after surgery.

A cytotoxic ribonuclease which specifically cleaves four isoaccepting arginine tRNAs at their anticodon loops.

Colicin D has long been thought to stop protein synthesis in infected Escherichia coli cells by inactivating ribosomes, just like colicin E3. Here, we show that colicin D specifically cleaves tRNAs(Arg) including four isoaccepting molecules both in vivo and in vitro. The cleavage occurs in vitro between positions 38 and 39 in an anticodon loop with a 2',3'-cyclic phosphate end, and is inhibited by a specific immunity protein. Consistent with the cleavage of tRNAs(Arg), the RNA fraction of colicin-treated cells significantly reduced the amino acid-accepting activity only for arginine. Furthermore, we generated a single mutation of histidine in the C-terminal possible catalytic domain, which caused the loss of the killing activity in vivo together with the tRNA(Arg)-cleaving activity both in vivo and in vitro. These findings show that colicin D directly cleaves cytoplasmic tRNAs(Arg), which leads to impairment of protein synthesis and cell death. Recently, we found that colicin E5 stops protein synthesis by cleaving the anticodons of specific tRNAs for Tyr, His, Asn, and Asp. Despite these apparently similar actions on tRNAs and cells, colicins D and E5 not only exhibit no sequence homology but also have different molecular mechanisms as to both substrate recognition and catalytic reaction.

Using HOS for characterization of periodical and time-varying waveform.

We applied an approach based on high order statistics (HOS) to classification of time series. This is different from most of the prior analyses in which signal features have been compared. In our approach, we investigate an input signal deformed non-linearly in time and contaminated with additional different forms of noise, e.g. Gaussian, non-Gaussian and their mixed form. The bispectrum-averaging technique (third order statistics) which preserves information about both amplitude and phase of the Fourier transform is studied for the reconstruction of the predictable waveform. The technique does require neither an initial estimate nor a peak-to-peak synchronization of the realizations. Thus, the normal waveform is considered ideally to be smooth and entirely predictable. The residual is characterized by subtracting the predictable part from the original waveform. Under non-linearity assumption, we propose that the Volterra process tool is suitable for analysis and differentiation between the patterns contained in the time series residual. We present and classify some results of the output of the linear transfer function of the process. The approach is numerically tested with the use of computer-generated data. Its effectiveness in dealing with electrocardiogram (ECG)-related data is also demonstrated.

[Usefulness of temporal subtraction images of chest computed radiography for detection of metastatic pulmonary nodules].

Temporal subtraction is a technique by which a previous chest radiograph is subtracted from a current radiograph in order to enhance interval changes. Our purpose in this study was to evaluate the usefulness of temporal subtraction for the detection of metastatic pulmonary nodules. We examined 19 cases of metastatic nodules less than 15 mm in diameter (8.4 mm on average). Temporal subtraction images were created based on the matching of local lung areas in pairs of chest radiographs. By using the subtraction images, the detectability of nodules was clearly improved in 5 cases and moderately improved in 8 cases; there was no improvement in 6 cases. The subtraction images were especially useful for nodules superimposed over normal structures, such as rib, mediastinum, and diaphragm, as well as for small nodules. In 6 of the 19 cases, the nodules had been missed clinically; however, the temporal subtraction images clearly demonstrated half of missed small nodules. Temporal subtraction made it possible to enhance subtle interval changes and helped in detecting small pulmonary metastases. This technique seems promising for augmenting the capabilities of computed radiography of the chest.