Standardized MR Perfusion Scoring System for Evaluation of Sequential Perfusion Changes and Surgical Outcome of Moyamoya Disease.

BACKGROUND AND PURPOSE: Simple-but-precise evaluation of cerebral perfusion is crucial for the treatment of Moyamoya disease. We aimed to develop a standardized scoring system for MR perfusion suitable for Moyamoya disease evaluation and investigate the postoperative serial changes and outcome predictors. MATERIALS AND METHODS: From January 2013 to December 2016, patients diagnosed with Moyamoya disease and receiving indirect revascularization were recruited prospectively. Clinical data and serial imaging studies were analyzed. The TTP maps were standardized using cerebellar reference values. We developed a scoring system of standardized TTP maps: 14 points for each hemisphere with higher points indicating better perfusion. RESULTS: In total, 24 children (4-17 years of age, 41 hemispheres) and 20 adults (18-51 years of age, 34 hemispheres) were included. The mean preoperative TTP scores were higher in children (7.34 ± 3.90) than in adults (4.88 ± 3.24). The standardized TTP maps revealed dynamic improvement with an increase in the corresponding scores at the 1-, 3-, and 6-month postoperative follow-ups; the scores stabilized after 6 months. The mean improvement in the 6-month scores of the pediatric and adult groups was 4.15 ± 3.55 and 6.03 ± 3.04, respectively. The 6-month TTP score improvements were associated with Matsushima grades. If we took score improvement as the outcome, the preoperative TTP score was the only significant predictor in multivariable analysis. CONCLUSIONS: The standardized TTP maps and scoring system facilitated the quantification of the sequential perfusion changes during Moyamoya disease treatment. The preoperative perfusion status was the only predictor of indirect revascularization outcome.

NMDA Receptor-Mediated Motor Cortex Plasticity After 20 Hz Transcranial Alternating Current Stimulation.

Transcranial alternating current stimulation (tACS) has been shown to modulate neural oscillations and excitability levels in the primary motor cortex (M1). These effects can last for more than an hour and an involvement of N-methyl-d-aspartate receptor (NMDAR) mediated synaptic plasticity has been suggested. However, to date the cortical mechanisms underlying tACS after-effects have not been explored. Here, we applied 20 Hz beta tACS to M1 while participants received either the NMDAR antagonist dextromethorphan or a placebo and the effects on cortical beta oscillations and excitability were explored. When a placebo medication was administered, beta tACS was found to increase cortical excitability and beta oscillations for at least 60 min, whereas when dextromethorphan was administered, these effects were completely abolished. These results provide the first direct evidence that tACS can induce NMDAR-mediated plasticity in the motor cortex, which contributes to our understanding of tACS-induced influences on human motor cortex physiology.

Compromised neuroplasticity in cigarette smokers under nicotine withdrawal is restituted by the nicotinic α4ß2-receptor partial agonist varenicline.

Nicotine modulates neuroplasticity and improves cognitive functions in animals and humans. In the brain of smoking individuals, calcium-dependent plasticity induced by non-invasive brain stimulation methods such as transcranial direct current stimulation (tDCS) and paired associative stimulation (PAS) is impaired by nicotine withdrawal, but partially re-established after nicotine re-administration. In order to investigate the underlying mechanism further, we tested the impact of the α4ß2-nicotinic receptor partial agonist varenicline on focal and non-focal plasticity in smokers during nicotine withdrawal, induced by PAS and tDCS, respectively. We administered low (0.3 mg) and high (1.0 mg) single doses of varenicline or placebo medication before stimulation over the left motor cortex of 20 healthy smokers under nicotine withdrawal. Motor cortex excitability was monitored by single-pulse transcranial magnetic stimulation-induced motor evoked potential amplitudes for 36 hours after plasticity induction. Stimulation-induced plasticity was absent under placebo medication, whereas it was present in all conditions under high dose. Low dose restituted only tDCS-induced non-focal plasticity, producing no significant impact on focal plasticity. High dose varenicline also prolonged inhibitory plasticity. These results are comparable to the impact of nicotine on withdrawal-related impaired plasticity in smokers and suggest that α4ß2 nicotinic receptors are relevantly involved in plasticity deficits and restitution in smokers.

Partially non-linear stimulation intensity-dependent effects of direct current stimulation on motor cortex excitability in humans.

Transcranial direct current stimulation (tDCS) of the human motor cortex at an intensity of 1 mA with an electrode size of 35 cm(2) has been shown to induce shifts of cortical excitability during and after stimulation. These shifts are polarity-specific with cathodal tDCS resulting in a decrease and anodal stimulation in an increase of cortical excitability. In clinical and cognitive studies, stronger stimulation intensities are used frequently, but their physiological effects on cortical excitability have not yet been explored. Therefore, here we aimed to explore the effects of 2 mA tDCS on cortical excitability. We applied 2 mA anodal or cathodal tDCS for 20 min on the left primary motor cortex of 14 healthy subjects. Cathodal tDCS at 1 mA and sham tDCS for 20 min was administered as control session in nine and eight healthy subjects, respectively. Motor cortical excitability was monitored by transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials (MEPs) from the right first dorsal interosseous muscle. Global corticospinal excitability was explored via single TMS pulse-elicited MEP amplitudes, and motor thresholds. Intracortical effects of stimulation were obtained by cortical silent period (CSP), short latency intracortical inhibition (SICI) and facilitation (ICF), and I wave facilitation. The above-mentioned protocols were recorded both before and immediately after tDCS in randomized order. Additionally, single-pulse MEPs, motor thresholds, SICI and ICF were recorded every 30 min up to 2 h after stimulation end, evening of the same day, next morning, next noon and next evening. Anodal as well as cathodal tDCS at 2 mA resulted in a significant increase of MEP amplitudes, whereas 1 mA cathodal tDCS decreased corticospinal excitability. A significant shift of SICI and ICF towards excitability enhancement after both 2 mA cathodal and anodal tDCS was observed. At 1 mA, cathodal tDCS reduced single-pulse TMS-elicited MEP amplitudes and shifted SICI and ICF towards inhibition. No significant changes were observed in the other protocols. Sham tDCS did not induce significant MEP alterations. These results suggest that an enhancement of tDCS intensity does not necessarily increase efficacy of stimulation, but might also shift the direction of excitability alterations. This should be taken into account for applications of the stimulation technique using different intensities and durations in order to achieve stronger or longer lasting after-effects.

Pyridoxal phosphate is better than pyridoxine for controlling idiopathic intractable epilepsy.

AIM: To study the difference between pyridoxine (PN) and its active form, pyridoxal phosphate, (PLP) in control of idiopathic intractable epilepsy in children. METHODS: Among 574 children with active epilepsy, 94 (aged 8 months to 15 years) were diagnosed with idiopathic intractable epilepsy for more than six months. All received intravenous PLP 10 mg/kg, then 10 mg/kg/day in four divided doses. If seizures recurred within 24 hours, another dose of 40 mg/kg was given, followed by 50 mg/kg/day in four divided doses. For those patients whose seizures were totally controlled, PLP was replaced by the same dose of oral PN. If the seizure recurred, intravenous PLP was infused followed by oral PLP 50 mg/kg/day. RESULTS: Fifty seven patients had generalised seizures (of whom 13 had infantile spasms) and 37 had focal seizure. Eleven had dramatic and sustained responses to PLP; of these, five also responded to PN. Within six months of treatment with PLP or PN, five of the 11 patients were seizure free and had their previous antiepileptic medicine tapered off gradually. Two were controlled with pyridoxine and the other three needed PLP to maintain seizure freedom. The remaining six responders needed PLP exclusively for seizure control. Six of the 11 responders to PLP had infantile spasms (46%); four of them needed PLP exclusively. The other five responders were in the remaining 81 patients with other seizure type. CONCLUSIONS: PLP could replace PN in the treatment of intractable childhood epilepsy, particularly in the treatment of infantile spasms.

Cervical cord tethering mimicking focal muscular atrophy.

Spinal cord tethering rarely occurs in the cervical region. In adults, it usually results from previous operations. However, congenital origin is always diagnosed and treated early in the infant period. We report a 12-year-old boy with cervical spinal dysraphism which was erroneously diagnosed as focal muscular atrophy, a benign form of motor neuron disease. The patient was brought to our hospital because of rapid deterioration of symptoms. Careful evaluation disclosed a hairy dimple at the nuchal area, which led to the correct diagnosis. X-ray of the cervical spine showed spina bifida from C(4) to C(6) levels and fusion of the laminae of C(4) and C(5). Spine MRI studies disclosed that the cervical cord was tethered caudally and dorsally, and the ventral nerve roots were markedly stretched, especially over the left side. Surgical intervention was undertaken and the patient's muscle power improved after untethering. The purpose of this report is to acquaint the reader with a surgically treatable condition that may appear to be benign focal amyotrophy. Skin lesion at the nuchal area should be carefully looked for.

Multimodal approach of cranial ultrasound in children.

The potential uses of cranial ultrasound have been overlooked for years because of the advent of fascinating neuroimaging studies such as computed tomography (CT) and magnetic resonance imaging (MRI) study. In this article, the authors introduce the developments and refinement in modern pediatric neurosonology. In the past, only neonates with widely open fontanels seemed to be good candidates for cranial ultrasound study. Actually, any tiny skull defect can be used as an acoustic window. And the thin skulls of children do not hinder the ability of ultrasound to obtain acceptable image transcranially. Today, many CT and MRI studies can be replaced with the advanced cranial ultrasound if clinicians or neurologists recognize the advantages. Cranial ultrasound can provide Doppler hemodynamic studies which CT and MRI can not. Only ultrasound can provide convenient, real-time intraoperative guidance and continuous bedside monitoring in patients who need neurological intensive care. Cranial ultrasound also plays an important role in follow-up studies because it is convenient, economical, and safe, especially in children. To obtain all the benefits from an ultrasound study, one has to realize the "multimodal" applications of it, including the applications of all acoustic windows, multifrequency transducers, and hemodynamic study with the aid of power Doppler and contrast agents. With a multimodal approach, physicians can achieve the utmost from the powerful modern cranial ultrasound in pediatric patients.

CPP antagonizes hypoxia-induced changes in dopamine metabolism in the striatum of newborn rat.

Treatment with 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), a potent and competitive N-methyl-D-aspartate antagonist, is able to reduce the hypoxia-induced increase in striatal dopamine level by 26% even after the hypoxic insult has occurred. The hypoxia-induced decrease of the striatal 3,4-dihydroxyphenylacetic acid level can also be reversed by CPP. This study demonstrates that CPP can antagonize the hypoxia-induced changes in the dopamine metabolism in the striatum of the newborn rat.

Distribution and expression of the subunits of N-methyl-D-aspartate (NMDA) receptors; NR1, NR2A and NR2B in hypoxic newborn piglet brains.

The purpose of this study was to identify the distribution and the expression of the NR1, NR2A and NR2B subunits of the NMDA receptor after cerebral hypoxia. Ten piglets were divided into control and hypoxic groups (n=5, each). The control piglets were ventilated with normoxia for 1 h, and the hypoxic piglets were ventilated with hypoxia until paO2 was below 20 mmHg. Tissue samples from the nine different regions of newborn piglet brain were obtained, and the protein amount of the NR1, NR2A, and NR2B subunits measured by immunoblot using the antibody to the NR1, NR2A, and NR2B subunits. The NR1, N2A, and NR2B subunits were distributed very differently; hippocampus and cortical area are more prominent than white matter and cerebellum. But the expression of the NR1, NR2A and NR2B subunits were not significantly different between the control and the hypoxic group, 1 h after hypoxic exposure, indicating no changes in the protein amount of NMDA receptor subunits. These results show a significantly higher amount of the NR1, NR2A and NR2B subunits in the hippocampus and the cerebral cortex of newborn brains, indicating that these structures could be highly vulnerable to excitotoxicity in the newborn brain.

Excitatory amino acid receptor antagonists decrease hypoxia induced increase in extracellular dopamine in striatum of newborn piglets.

The present study tested the hypothesis that the increase in extracellular striatal dopamine during hypoxia is least partly associated with activation of N-methyl-D-aspartate (NMDA) and/or non-NMDA excitatory amino acid receptors. Studies were performed in anesthetized and mechanically ventilated 2-3 days old piglets. Hypoxic insult was induced by decreasing the oxygen fraction in inspired gas (FiO2) from 22 to 7% for 1 h, followed by 1 h reoxygenation at 22%. Cortical oxygen pressure was measured optically by oxygen dependent quenching of phosphorescence, and extracellular striatal dopamine was measured using in vivo microdialysis. The microdialysis probes were perfused with Ringer solution +/- 50 microM (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) or 50 microM 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX). One hour of hypoxia decreased the cortical oxygen pressure from 46 +/- 3 Torr to 10 +/- 1.8 Torr. In striatum perfused with Ringer, statistically significant increase in extracellular dopamine, to 1050 +/- 310% of control, was observed after 20 min of hypoxia. By 40 min of hypoxia the extracellular level of dopamine increased to 4730 +/- 900% of control; by the end of the hypoxic period the values increased to 18,451 +/- 1670% of control. The presence of MK-801 in the perfusate significantly decreased the levels of extracellular dopamine during hypoxia. At 20, 40 and 60 min of hypoxia extracellular level of dopamine increased to 278 +/- 94% of control, 1530 +/- 339% of control and 14,709 +/- 1095 of control, respectively. The presence of NBQX caused a statistically significant decrease, by about 30%, in the extracellular dopamine compared to control, only at the end of the hypoxic period. It can be concluded that in striatum of newborn piglets, the excitatory NMDA receptors but not the non-NMDA receptors may be modulating the changes in extracellular levels of dopamine. The NMDA receptor antagonist, MK-801, may exert part of its reported neuroprotective effect to hypoxic stress in striatum by decreasing the levels of extracellular dopamine.

Combined encephalo-arterio-synangiosis and encephalo-myo-synangiosis in the treatment of moyamoya disease.

From January 1990 to December 1995, a total of nine cases of Moyamoya disease were treated at the National Taiwan University Hospital with combined encephalo-arterio-synangiosis (EAS) and encephalo-myo-synangiosis (EMS). There were five males and four females and their ages ranged from 6 months to 31 years. Of these, two cases had their first symptom as intracranial hemorrhage and the rest of the cases had ischemic manifestations. Surgical treatment with combined EAS and EMS was performed on 16 hemispheres of the nine cases. The superficial temporal artery with its anterior and posterior branches was isolated and fixed to the pial surface. Then, the muscle pedicle from the bivalved temporal muscle was used as a dural graft to cover the artery. All the cases showed good neovascularization on follow-up angiography performed at 2-3 months after surgery. These two patients with hemorrhagic symptoms were followed for 52 and 61 months, respectively. Neither of these two cases showed recurrent bleeding. For patients with ischemic symptoms, the follow-up period ranged from 8 to 73 months (mean 41.7 months). All the patients showed improvement in their clinical symptoms.

Cerebral oxygen transport and metabolism during graded isovolemic hemodilution in experimental global ischemia.

To verify the optimal hematocrit (Hct) level in the treatment of cerebral ischemia, cerebral oxygen transport (CTO2) and cerebral oxygen metabolism (CMRO2) in graded isovolemic hemodilution were evaluated during cerebral ischemia. Isovolemic hemodilution with low molecular weight dextran to stepwise lower Hct from 43% to 36%, 31%, and 26% was carried out in 13 splenectomized dogs, 6 h after global cerebral ischemia. Global ischemia of the animals was produced by multiple intra- and extracranial ligations of cerebral arteries. Cerebral blood flow (CBF) was measured with radioisotope labeled microspheres. CTO2, CMRO2, and oxygen extraction fraction (OEF) were calculated from CBF, arterial oxygen content (CaO2), and venous oxygen content (CvO2). In dogs with global cerebral ischemia, CBF increased with graded isovolemic hemodilution (r=-0.73, P<0.05). CTO2 reached its highest value at a Hct level of 31.3%. CTO2 at Hct of 36.1% and 31.3% was statistically different from the value measured at a Hct of 43.3%, and there was a decrease when Hct was lowered to 25.9%. CMRO2 was the highest when Hct was at 31.3% and differed significantly from the value measured at a Hct of 43.3%. There was a 10% increase of OEF when Hct was at 25.9%; however this change was not statistically significant compared with the OEF at Hct of 36.1% and 31.3%, respectively. These findings indicate that CTO2 and CMRO2 were the highest when Hct was reduced to 31% in hemodilution. Hct at 31% is the optimum for cerebral metabolism in ischemic status. Uncoupling of CTO2, CMRO2 with CaO2 was also observed in this study. This phenomenon suggests that hemodilution to augment cerebral circulation may be at least partially attributed to the beneficial effects of hemorheologic improvement in the microcirculation of the ischemic brain.

Supraorbital approach of the anterior cerebral artery: a new window for transcranial Doppler sonography.

Usually, a transtemporal Doppler sonographic study of the anterior cerebral artery can insonate the A1 segment only. We found a new window just above the supraorbital ridge to approach the A2 segment and even the proximal portion of the pericallosal segment in 17 of 21 volunteers aged from 16 months to 39 years. The failed four cases had an average age of 23 years. We suggest that the supraorbital approach can be tried as another window during transcranial Doppler sonographic examinations, especially in the young patient and in those for whom the transtemporal approach has failed.

Sonographic lenticulostriate vasculopathy in infants: some associations and a hypothesis.

PURPOSE: To describe the causes of infantile lenticulostriate vasculopathy (LSV) as demonstrated by sonography and propose the pathogenesis of these findings. METHODS: Five hundred eighty-six infants were examined via echoencephalography because of seizures, psychomotor retardation, dysmorphism, congenital malformation, microcephaly, macrocephaly, bulging of anterior fontanel, consciousness disturbance, or prematurity. We directed our attention on the sonographic study to the basal ganglionic and thalamic areas. Twenty-eight of the 586 patients underwent color Doppler studies. RESULTS: In 34 infants with gray-scale neurosonographic findings of LSV, 16 were associated with various causes that have been reported before. In 8 patients entities not previously associated with LSV were found: neonatal lupus, neonatal hypoglycemia, uncomplicated prematurity, encephalitis, and head injury. In the remaining 10 cases, a specific cause could not be found. The LSV was found in 16 (40%), 5 (14%), and 13 (3%) patients with perinatal, acquired, and nonspecific causes, respectively. Generally, this is an uncommon finding because it was observed in only 34 (5.8%) of the study infants; 24 of these 34 had a documented cause of the vasculopathy. With LSV associated with perinatal causes there was a greater chance of sonographic LSV's developing than with that of acquired causes. CONCLUSIONS: We suggest that sonographic LSV is a nonspecific marker of a previous insult to the developing brain, and the special hemodynamics of the fetal brain plays an important role in its pathogenesis.

Spinal intradural arteriovenous fistula: a case with an unusual presentation.

Spinal intradural arteriovenous fistula is a rare type of spinal vascular malformation. It is usually fed by the anterior spinal artery and causes episodic myelopathy in young adults. We present a pediatric patient with such a vascular malformation which was fed directly by a medullary artery. The clinical course, complete radiological study and the excellent outcome will be described in detail. This rare subtype of spinal vascular malformation will be discussed.

Choreoathetosis as an initial sign of relapsing of herpes simplex encephalitis.

Twelve children with type 1 herpes simplex encephalitis (3 with relapse, 9 without) have been monitored during the past 7 years. Ten of the children received intravenous infusion of acyclovir (30 mg/kg/day) for 10 days, 1 child who experienced relapse received 15 mg/kg/day, and another relapsed child received no antiviral agents until relapse. Relapse occurred 20-36 days after initial onset. All relapsed patients underwent another 10 days of acyclovir treatment (30 mg/kg/day). Choreoathetosis appeared as the initial sign of relapse followed by rapidly progressive unresponsiveness in all 3 relapsed patients: in 1 nonrelapsed patient choreoathetosis occurred during the recovery period. In these 4 patients involuntary movement was remitted within 3 months to 2 years. One patient with choreoathetosis died of measles pneumonia 4 months after onset of herpes simplex encephalitis and the surviving 3 were severely retarded. Although neuroimaging sparing of basal ganglia does not indicate structural and functional abnormalities, the disturbance of the neural connection among the basal ganglia and the cerebral cortex, which manifested severe damage over frontal, temporal, and parietal mantles on CT, may be the source of movement disorders in these patients. We conclude that choreoathetosis may be the first sign of relapse of herpes simplex encephalitis in children and may be an indicator of poor prognosis. The neuropathogenesis of choreoathetosis requires further investigation.

Percutaneous lumbar discectomy: indications and surgical results in 35 consecutive cases.

Thirty-five patients (27 men and eight women) who met our criteria of case selection for percutaneous lumbar discectomy (PLD) were treated by this method during the period May 1992 to June 1993. Thirty-six spaces, including one man with double disc disease, were decompressed. Patients ranged in age from 14 to 64 years. All patients but one were followed up for a minimum of six months. The operative results, evaluated by a more objective functional grading system, revealed a short-term (two months) success rate of 83% and a mid-term (six months) success rate of 76%. This discrepancy resulted from two recurrences of sciatic symptoms. It indicates that the medical conditions of those who have received PLD are by no means static, but instead may fluctuate. The operative result was similar to that of open discectomy, averaging 81.1% in reported series. Our "functional grading system" reflects these fluctuations quantitatively. With respect to the operative success rate, there was a statistical difference between the very good, good and fair-poor indication groups of patients, as were categorized by our major criteria of indications that included three clinical manifestation criteria and the other three radiographic findings. This result emphasizes the critical role of case selection in the operative success rate. Complications consisted of one disc infection which cleared without sequelae. This study provides an objective means of selecting cases and evaluating surgical results which, in turn, makes the use of this procedure convincing and predictable.

Solitary cerebellar metastasis from Ewing's sarcoma: case report and review of the literature.

A rare case of Ewing's sarcoma metastatic to the cerebellum is presented. Neurosurgical intervention was required which played a significant role in the treatment of this patient. The incidence and treatment of central nervous system involvement from Ewing's sarcoma is reviewed and discussed.

Medical cure of a brainstem abscess and serial brainstem auditory evoked potentials.

The brainstem abscess of a nine-year-old girl with tetralogy of Fallot was cured after six weeks of parenteral antibiotic therapy, without surgical intervention. Serial studies of brainstem auditory evoked potentials were undertaken until the patient was clinically normal. To the authors' knowledge, this is only the second medically cured case reported in the literature, and it is the first case studied with serial brainstem auditory evoked potentials. If the clinical status allows, medical treatment of a brainstem abscess with appropriate antibiotics could be tried before surgical intervention such as stereotactic aspiration for reducing the mass.