Arata Watanabe

Effect of intracranial pressure on the diameter of the optic nerve sheath

OBJECT The subarachnoid space around the optic nerve in the orbit can be visualized using T2-weighted MR imaging with the fat-saturation pulse sequence. The optic nerve sheath (ONS) diameter can be estimated by measuring the outer diameter of the subarachnoid space. Dilated ONS is associated with idiopathic intracranial hypertension and hydrocephalus, and is believed to reflect increased intracranial pressure (ICP). The relationship between dilated ONS and ICP is unclear because of the difficulty in obtaining noninvasive measurements of ICP. The authors investigated the relationship between subdural pressure measured at the time of surgery and ONS diameter measured on MR images in patients with chronic subdural fluid collection. METHODS Twelve patients underwent bur-hole craniostomy with continuous drainage for chronic subdural hematoma or hygroma in 2006. Orbital thin-slice fat-saturated MR images were obtained before and after surgery, and the ONS diameters were measured just behind the optic globe. Subdural pressure was measured using a manometer before opening of the dura mater. RESULTS A significant correlation was found between the ONS diameter and the subdural pressure (correlation coefficient 0.879, p = 0.0036). The ONS diameter before surgery (6.1 +/- 0.7 mm) was significantly reduced after surgery (4.8 +/- 0.9 mm, p = 0.003; measurements are expressed as the mean +/- standard deviation). CONCLUSIONS Increased ONS diameter measured on coronal orbital thin-slice fat-saturated T2-weighted MR images is a strong indicator of increased ICP, and helps to differentiate between passive subdural fluid collection due to brain atrophy and subdural hygroma with increased ICP.

Regional brain serotonin synthesis is increased in the olfactory bulbectomy rat model of depression: an autoradiographic study

Serotonin synthesis rates were evaluated using α‐[14C]methyl‐l‐tryptophan (α‐MTrp) autoradiographic methods in olfactory bulbectomized (OBX) rats. They were significantly (p < 0.05) increased in the frontal (50%) and parietal (40%) cortices, superior olive (over 30%), and the substantia nigra (30%) in the OBX rats as compared to the sham operated animals. There were also increases in 5‐hydroxytryptamine (5‐HT) synthesis in some limbic areas: the cingulate (32%), the medial forebrain bundle (58%), the hippocampus (13–25%) and the thalamus (22–40%). The largest increase in 5‐HT synthesis after OBX was observed in the sensory‐motor cortex (67%). 5‐HT synthesis rates were significantly decreased in the dorsal and medial raphe nuclei, but there was no significant change the ventral tegmental area and the locus coeruleus following OBX. These results indicate that olfactory bulbectomy causes an imbalance in 5‐HT synthesis in some projection areas by disproportionally increasing 5‐HT synthesis rates in specific brain regions and making more 5‐HT available for neurotransmission. This imbalance in 5‐HT synthesis and the subsequent elevation of tissue 5‐HT may be responsible for the creation of non‐physiological circuitry which may, in part, be reflected in the symptoms resembling human depression.

Chronic administration of citalopram in olfactory bulbectomy rats restores brain 5-HT synthesis rates: an autoradiographic study

RationaleThe olfactory bulbectomized (OBX) rat model is widely accepted as an animal model of depression with a proposed serotonergic imbalance in the brain.ObjectiveTo study the effects of chronic administration of citalopram on serotonin (5-HT) synthesis rates.MethodSerotonin synthesis was evaluated using the α-[14C]methyl-l-tryptophan (α-MTrp) autoradiographic method in OBX rats. Citalopram was administered continuously (10 mg kg−1 day−1) for 14 days using a subcutaneous osmotic minipump.ResultsThe OBX rats treated with citalopram (OBX-CTP) have the same 5-HT synthesis rates as the sham-operated rats treated with citalopram (Sham-CTP). The OBX-CTP rats, relative to the OBX rats treated with saline (OBX-SAL), showed a reduction in the majority of the terminal brain structures, suggesting a normalization of 5-HT synthesis in the OBX-CTP rats following treatment. The OBX-SAL rats have significantly greater synthesis than the Sham-SAL rats in a majority of the terminal structures, but lower rates in the dorsal raphe. A few structures in the OBX-CTP group have lower synthesis than in the Sham-SAL group (e.g., dorsal raphe, hippocampus, amygdala). The data suggest that receptors in some brain areas are likely still responsive to the elevated levels of the extracellular 5-HT produced by citalopram.ConclusionThere is no significant global or individual structure difference in the synthesis between the Sham-CTP and OBX-CTP groups. The similarity in the synthesis between the OBX-CTP, Sham-CTP and Sham-SAL groups is likely a result of changes in the sensitivity of the receptors through which 5-HT synthesis is controlled. Because of some of the differences in the synthesis between the Sham-CTP and Sham-SAL groups, the data suggest that receptors throughout the brain are not fully desensitized.

The inhibition of tryptophan hydroxylase, not protein synthesis, reduces the brain trapping of α-methyl-L-tryptophan: an autoradiographic study

The effects of the tryptophan hydroxylase (TPH) inhibitor p-chlorophenylalanine (PCPA; 200mg/kg; 3 days), and of the protein synthesis inhibitor cycloheximide (CXM, 2mg/kg), on regional serotonin (5-HT) synthesis were studied using the alpha-[14C]methyl-L-tryptophan (alpha-[14C]MTrp) autoradiographic method. The objectives of these investigations were to evaluate the changes, if any, on 5-HT synthesis, as measured with alpha-MTrp method, following the inhibition of TPH by PCPA, or the inhibition of proteins synthesis by CXM. The rats were used in the tracer experiment approximately 24h after the last dose of PCPA was administered, and in the CXM experiments, they were used 30 min following a single injection of CXM. In both experiments, the control rats were injected with the same volume of saline (0.5 ml/kg; s.c.) and at the same times as the drug injections. The results demonstrate that trapping of alpha-MTrp, which is taken to be related to brain 5-HT synthesis, is drastically reduced (40-80%) following PCPA treatment. The inhibition of protein synthesis with CXM did not have a significant effect on the global brain trapping of alpha-MTrp and 5-HT synthesis. These findings suggest that the brain trapping of alpha-[14C]MTrp relates to brain 5-HT synthesis, but not to brain protein synthesis.

Selective 5-HT1B receptor agonist reduces serotonin synthesis following acute, and not chronic, drug administration: results of an autoradiographic study.

The effects of acute and chronic administration of the serotonin (5-HT)1B agonist CP-93,129, on 5-HT synthesis rates were evaluated using the alpha-[14C]methyl-L-tryptophan (alpha-MTrp) autoradiographic method. In the acute treatment study, CP-93,129 (7 mg/kg) was injected intraperitoneally 30 min before the alpha-MTrp injection (30 microCi over 2 min). A single dose of CP-93,129 caused a significant increase in the synthesis in the median raphe nucleus (MR) without a significant influence on the dorsal raphe nucleus (DR). There was a reduction in 5-HT synthesis in almost all of the projection areas. In the chronic treatment study, CP-93,129 was administered continuously (7 mg/kg/day) for 14 days using an osmotic minipump implanted subcutaneously. The chronic treatment with CP-93,129 did not produce a significant change in 5-HT synthesis in the raphe nuclei nor in the nerve terminal structures, except for the medial frontal bundle and the visual and sensory-motor cortices. The unaltered 5-HT synthesis rates in the chronic treatment study probably reflect a normalization of the synthesis as a result of the desensitization of 5-HT1B autoreceptors and/or heteroreceptors.

Chronic buspirone treatment normalizes regional serotonin synthesis in the olfactory bulbectomized rat brain: An autoradiographic study

The effects of chronic buspirone treatments, administered by minipump at doses of 10 and 20 mg/(kg day) for 14 days, on brain 5-HT synthesis in olfactory bulbectomized (OBX) rats were evaluated. The alpha-[14C]methyl-L-tryptophan autoradiographic method was used. We compared the synthesis in the buspirone treated OBX rats (administered either 10 mg/(kg day) (OBX-10) or 20 mg/(kg day) (OBX-20)) to that of the saline treated OBX rats (OBX-SAL), and the sham operated rats (SHX) treated with saline. In addition, OBX-10 rats were compared to SHX rats treated with 10 mg/(kg day) (SHX-10) of buspirone. All treatments were carried out for 14 days. Adult Sprague-Dawley rats were used. Two weeks following the OBX or SHX procedures, the rats were assigned to the OBX-10, OBX-20, OBX-SAL, SHX-10, or SHX-SAL groups, respectively. The 5-HT synthesis rates R (pmol/(g/min)) were calculated from the trapping constant of alpha-[14C]MTrp (K*; ml/(g min)) and the plasma concentration of the plasma non-protein-bound tryptophan (Cp; pmol/ml) using the lumped constant (LC) measured previously in the rat brain. There was no significant difference in the plasma free or total tryptophan among these groups. The overall synthesis in the OBX-10 group was not statistically different from the OBX-SAL group, but it was different from the OBX-20 and SHX-SAL groups. The OBX-20 rats had an overall significant reduction in 5-HT synthesis, when compared to the OBX-SAL group, but did not differ from the SHX-SAL group, which did not differ from the SHX-10 group. These results suggest that 10 mg/(kg day) of buspirone for 14 days in the OBX rats did not produce a significant alteration in 5-HT synthesis, but 20 mg/(kg day) for 14 days resulted in an overall significant reduction in brain 5-HT synthesis. The latter treatment brought the synthesis to the level found in the sham operated rats, i.e., a normal level. These results suggest that normalization (reduction to the level found in the SHX-SAL rats) of 5-HT synthesis in the OBX requires a greater dose of buspirone (20 mg/(kg day)) than that needed to produce a desensitization of the 5-HT1A receptors in the sham operated rats (10 mg/(kg day)). This probably indicates that 5-HT1A receptors have different functionality in the OBX rats than that found in the intact or sham operated rats. Furthermore, our results support the hypothesis that 5-HT1A receptors mediate the antidepressant-like effect of 5-HT1A agonists, as the chronic 5-HT1A agonist treatment in the depression model known to be sensitive to antidepressants resulted in the normalization of 5-HT synthesis.

Effectiveness of an epidural blood patch for patients with intracranial hypotension syndrome and persistent spinal epidural fluid collection after treatment

OBJECT Magnetic resonance imaging may show a fluid collection in the spinal epidural space of patients with spontaneous intracranial hypotension syndrome (SIHS), but the chronological changes remain unclear. METHODS Brain and spine MR imaging findings were analyzed in 16 patients (9 women and 7 men, mean age 48.6 years) with SIHS before and after treatment. RESULTS Diffuse dural enhancement was seen in 15 patients, and the epidural fluid collection in the spinal canal was clear in 15 and equivocal in 1. Symptoms disappeared after bed rest in 1 patient, and an epidural blood patch was performed in 15 patients, resulting in complete resolution of symptoms in 13. After the follow-up period (range 1-20 months, mean 5.0 months), 1 patient had persistent mild headache that gradually worsened in the afternoon, and another patient complained of heaviness of the eyes. Follow-up MR imaging demonstrated disappearance of the dural enhancement in all patients, but a fluid collection in the spinal canal remained in 4. Two of the 4 patients had persistent symptoms, but the other patients exhibited complete resolution of the symptoms. CONCLUSIONS An epidural blood patch is effective for sealing of CSF leaks, but the resolution of SIHS-related symptoms does not always imply complete eradication of the leakage.

Diagnostic value of the optic nerve sheath subarachnoid space in patients with intracranial hypotension syndrome.

OBJECT The size of the subarachnoid space in the optic nerve sheath (ONS) on MR images is thought to reflect intracranial pressure. The diagnostic value of this space was investigated in patients with spontaneous intracranial hypotension (SIH) syndrome. METHODS Coronal fat-saturated T2-weighted MRI of the orbit was performed in 15 patients with SIH fulfilling the diagnostic criteria for headache caused by low CSF pressure of the International Classification of Headache Disorders or the criteria for spontaneous spinal CSF leaks and intracranial hypotension. The size of the subarachnoid space in the ONS was measured in 2 slices behind the eyeballs. The images were compared before and after treatment. The CSF pressure was measured by lumbar puncture. RESULTS Before treatment, the diameter of the ONS subarachnoid space ranged from 2.58 to 4.21 mm (mean 3.34 mm) and the thickness from 0 to 0.48 mm (mean 0.15 mm). Both measurements showed significant correlations with CSF opening pressure, and 8 patients had no CSF space before treatment. The size of CSF space increased in many patients after effective treatment. CONCLUSIONS Disappearance of the CSF space in the ONS was frequently observed in patients with SIH. This characteristic finding may be useful in the diagnosis of SIH as well as in the evaluation of treatment effectiveness.

Bony carotid canal hypoplasia in patients with moyamoya disease.

OBJECT The natural history of moyamoya disease is not well known. We have observed that the bony carotid canal is hypoplastic in patients with adult onset moyamoya disease. Bony carotid canal development should represent internal carotid artery (ICA) development, and may stop with the beginning of ICA stenosis. The purpose of this study was to determine the onset of moyamoya disease by measuring the bony carotid canal. METHODS The normal diameter of the bony carotid canal was evaluated on 4-mm thick bone window CT scans of the skull base in 60 Japanese patients aged 20-80 years, who had minor head trauma or headache considered to be unrelated to the skull base or arterial systems. The relationship between age and bony carotid canal development was assessed in a second group of 50 patients aged 0-19 years, including 10 under 2 years, using CT scans with the same parameters. The diameter of the bony carotid canal in 17 Japanese patients with moyamoya disease was measured. RESULTS The normal diameter in adults was 5.27 +/- 0.62 mm (mean +/- SD). The bony carotid canal developed rapidly before approximately 2 years of age. After fusion of the bony suture, the bony carotid canal developed slowly. The mean diameter of the bony carotid canal was 3.31 +/- 0.44 mm in 11 adult patients with adult-onset moyamoya disease. According to the apparent curve of bony carotid canal development, ICA stenosis was assumed to start in early childhood. CONCLUSIONS Our findings suggest that most cases of Asian moyamoya disease may arise in childhood and that many Asian adult patients with moyamoya disease may develop occlusive vasculopathy in childhood.

Jugular Compression and Radionuclide Cisternographic Patterns in Patients With Chronic Headache

Objective.—We investigated the value of the jugular compression test (JCT) in screening patients with chronic headache attributable to persistent cerebrospinal fluid (CSF) leakage.