The changes of c-Fos expression by motor cortex stimulation in the deafferentation pain model.

The effect of motor cortex stimulation (MCS) therapy for deafferentation pain was evaluated based on c-Fos, a known pain marker. Nineteen mature cats weighing 1.5-3.5 kg were used. Cats were divided into three groups: a deafferentation pain group in which the left trigeminal ganglion was destroyed, an MCS group in which MCS was used following destruction of the trigeminal ganglion, and a control group. Sites and levels of c-Fos expression were examined immunohistochemically. The percentage of c-Fos-positive cells in the left spinal nucleus of the trigeminus, the bilateral insula, and the bilateral operculum increased in both the deafferentation pain and the MCS groups. There were no statistically significant differences between these groups. In the cingulate gyrus, the percentage of c-Fos-positive cells increased bilaterally in the deafferentation pain group and the MCS group, but the increase was greater in the MCS group. The increase in c-Fos-positive cells in the left spinal nucleus of the trigeminus in the deafferentation group may reflect reported electrical hyperactivity. The cingulate gyrus, insula, and parietal operculum were activated after deafferentation. This change (increase in c-Fos positive cells) is related to the development of deafferentation pain. Pain relief due to MCS is not dependent on the suppression of the activated left spinal nucleus of the trigeminus or the descending analgesic mechanism of the brain stem. Activation of the cingulate gyrus appears to be a factor in the analgesic mechanism of MCS.

[Leiomyosarcoma of the uterus metastatic to the brain].

A case of 52-year-old female presented with dysarthria and paresis of right upper extremity 3 years after an operation and chemotherapy for uterine leiomyosarcoma. Magnetic resonance imaging showed an enhanced mass in the left corona radiata. Brain biopsy was carried out and pathological examination of the specimen showed features of a leiomyosarcoma. Uterine leiomyosarcoma is an uncommon tumor and its metastasis to the brain is rare. Only 13 other cases have been published. The patient underwent gamma-knife therapy and obtains good quality of life.

Usefulness of acellular dermal graft as a dural substitute in experimental model.

BACKGROUND: Friction injury of cortical surface or cerebrospinal fluid leakage are the major complications of polytetrafluoroethylene (ePTFE) duraplasty because of their strong surface tension and lesser adaptability. Autologous duraplasties are also accompanied by potential donor-site complications and are inappropriate for large defects. Acellular Dermal Graft (ADG), prepared from cadaver human skin, does not have the above-mentioned drawbacks because of its human nature. Moreover, the dermal basement membrane and supporting tissues remain intact, so the rate of cellular migration and transformation to the surrounding host tissue is supposed to be excellent. We studied ADG in canine model to observe the rate of transformation into the surrounding dura mater via collagen synthesis from the invaded fibroblasts to evaluate its usefulness as a duraplasty. METHODS: Dural grafting surgery was performed on 6 adult mongrel dogs weighing from 8 to 12 kgs under general anesthesia. Three dogs were sacrificed after 1 month (acute) of surgery and the other three (chronic) were sacrificed after 3 months with overdose of pentobarbital sodium. Transcardiac perfusion-fixation with 4% paraformaldehyde was done. Hematoxylin-eosin and trichrome masson stains were performed to see the graft cellularity. Thickness of grafts was also assessed along the length of the histologic sections. RESULTS: Duralization, which was microscopically characterized by infiltration with regular array of collagen fibers, was observed at a few places in every high-power field in acute group. But in chronic animals, where dermal side of ADG was facing towards cranium, duralization was excellent. CONCLUSIONS: Our result suggests that ADG can be considered as a useful dural substitute.

Assessment of vascular injury in patients with stroke by measurement of pulse wave velocity.

Vascular injury causes various diseases and may be especially important as a risk factor for stroke, and early diagnosis is useful for prevention of stroke. Recently, pulse wave velocity (PWV) has been receiving increasing attention as a noninvasive measurement of vascular injury. In this study, we investigated PWV of patients with stroke to determine the degree of vascular injury. PWV was measured in 114 patients with stroke, and the significance of differences between the PWV of stroke subgroups and that of the control group was investigated in an age- and sex-matched case-control study. In comparison with the control group, PWV was increased significantly in patients with intracerebral hemorrhage (P = .0107) and cerebral infarction (P < .0001). Of risk factors, hypertension and high PWV were independently related to the presence of intracerebral hemorrhage on multivariate analyses. Smoking and high PWV were found to be independent risk factors for cerebral infarction. A strong relationship between stroke and PWV was demonstrated. Measurement of PWV is useful for quantitatively assessing the progression of vascular injury, which may potentially be a risk factor for stroke.

A case of definitely congenital glioblastoma manifested by intratumoral hemorrhage.

BACKGROUND: A female infant was born with a left-sided glioblastoma that manifested clinically with weakened crying and feeding on day 1 of life, fever and bulging anterior fontanel on day 4, and right hemiparesis by day 10. METHODS: Preoperative magnetic resonance imaging showed hemosiderin intensity indicating that hemorrhage had occurred during the prenatal period. Radical surgical removal of the tumor was performed on the 22nd postnatal day. RESULTS: Postoperatively, the right hemiparesis did not worsen and the patient did not have any new neurological deficits. The right hemiparesis gradually improved after her initial surgery, and she was able to stand by herself at 18 months of age. Adjuvant chemotherapy and radiation were administered. This patient survived for 27 months following birth, which is a relatively long time for glioblastoma cases. Radical removal at the first operation with reliance on the plasticity of infant cerebral function was the key point in the long survival.

Role of a decreased expression of the local renin-angiotensin system in the etiology of cerebral aneurysms.

BACKGROUND: Local renin-angiotensin systems (RAS) have been implicated as playing an important role in vascular remodeling. The relationship of this system to the etiology of cerebral aneurysm was investigated. METHODS AND RESULTS: The aneurysmal wall from patients with a ruptured or unruptured cerebral aneurysm and the cortical cerebral artery in control patients with head trauma or a glioma were taken during surgery for study. Local RAS were evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and/or immunohistochemistry. RT-PCR analysis revealed a significantly decreased expression of angiotensin-converting enzyme (ACE), angiotensin type 1 (AT1) receptor, basic fibroblast growth factor, platelet-derived growth factor-AA, and tissue inhibitor of matrix metalloproteinases-1 mRNA in the aneurysmal wall as compared with the control cortical arterial wall. Immunohistochemistry also revealed a decreased expression of ACE, AT1 receptor, and angiotensin II in the aneurysmal wall. CONCLUSIONS: Expression of local RAS was decreased in the aneurysmal wall, which may induce aneurysm formation caused by a lack of vascular remodeling that prevents the arterial wall from thickening under increased hemodynamic stress. This is the first report that suggests that a decreased expression of local RAS plays a part in the pathogenesis of any disease.

Spontaneously ruptured craniopharyngioma cyst without meningitic symptoms --two case reports.

Two cases of spontaneous rupture of cystic craniopharyngioma without chemical meningitis are described. A 70-year-old woman complained of headache and visual field disturbance in July 1993. The tumor was extirpated in November 1993 and again in December 1996. After regular periodic follow-up evaluation, she was hospitalized for reoperation because of expansion of the cyst on magnetic resonance (MR) imaging in November 1998. However, preoperative MR imaging taken 8 weeks later revealed spontaneous reduction of the cyst. A 69-year-old woman noticed deteriorating vision and bitemporal hemianopsia in November 1998. The tumor was removed in December 1998, and 50.4 Gy postoperative radiotherapy was administered. MR imaging in May 2000 demonstrated an enlargement of the cyst, so she was hospitalized again for operation. However, preoperative MR imaging taken 7 weeks later showed spontaneous reduction of the cyst. Neither of the cases of cyst rupture were accompanied by symptoms of chemical meningitis. The signal intensity of the tumors on T1-weighted MR imaging declined after cyst reduction. Thereafter, the cysts increased in size again at 7 months and 5 months. Regular follow-up on MR imaging is necessary, since the cyst size can increase rapidly, even after spontaneous rupture.

Pituitary abscess showing high uptake of thallium-201 on single photon emission computed tomography--case report.

A 32-year-old female presented with a rare case of pituitary abscess manifesting as homonymous hemianopsia. Serum prolactin level was slightly high (40.8 ng/ml). Magnetic resonance (MR) imaging showed the content of the lesion as homogeneously isointense on the T1-weighted images and hyperintense on the T2-weighted images. The capsule of the lesion, which appeared thin and smooth, was enhanced by gadolinium. Dural enhancement around the sella turcica was also recognized. Thallium-201 single photon emission computed tomography (201Tl SPECT) showed homogeneous high accumulation in the pituitary region on both the early and delayed images. The lesion was treated via a transnasaltranssphenoidal approach. The cystic lesion contained pus and the capsule consisted of normal pituitary gland with inflammatory changes. The patient was treated with antibiotics for 3 weeks and the pituitary abscess was cured completely. Pituitary abscess can be differentiated from pituitary adenoma as lesion with a homogeneous high uptake on 201Tl SPECT on both the early and delayed images, and no enhancement of the central portion on MR images.

Risk factors for aneurysmal subarachnoid hemorrhage in Aomori, Japan.

BACKGROUND AND PURPOSE: Japan is known to have an incidence of aneurysmal subarachnoid hemorrhage (SAH) as high as that in Finland, where SAH is especially common. However, the risk factors for SAH in Japan are unknown. The purpose of this study was to identify the risk factors and then examine their possible roles in cases of SAH in Japan. METHODS: Case-control data were collected in the Aomori prefecture between June 2000 and May 2001 and in the Shimokita area between 1989 and 1998. A history of hypertension, cigarette smoking, alcohol consumption, hypercholesterolemia, and diabetes mellitus were examined as possible risk factors for SAH by using stepwise logistic regression analysis. RESULTS: Stepwise logistic regression analysis showed that a history of hypertension and current smoking increased the risk of SAH and that a history of hypercholesterolemia decreased the risk of SAH. Alcohol consumption and a history of diabetes mellitus were excluded from the model, because their log-likelihood ratios were not significant. The adjusted odds ratios, obtained by forcing matching factors, were 2.29 for a history of hypertension (95% CI, 1.66 to 3.16), 3.12 for current smoking (95% CI, 2.05 to 4.77), and 0.41 for a history of hypercholesterolemia (95% CI, 0.24 to 0.71). The prevalence of hypertension in control subjects was 27% in men and 31% in women, whereas the prevalence of cigarette smoking in control subjects was 46% in men and 9% in women. CONCLUSIONS: Hypertension and cigarette smoking seem to be independent risk factors for SAH in Japan. The high prevalence of hypertension in both sexes and the high prevalence of cigarette smoking in men in the general population might contribute to the high incidence of SAH in Japan.

Apoptosis of auditory neurons following central process injury.

Although apoptotic changes in auditory neurons induced by injury to peripheral processes (dendrites) have been intensively studied, apoptotic changes in auditory neurons induced by injury to central processes (axons of spiral ganglion cells, SGCs) have not been reported previously, probably due to lack of an experimental model. The present study reports for the first time the appearance, extent, and time course of SGC apoptosis following injury to the central processes. Apoptosis was studied in a rat model that consisted of compression of the auditory nerve in the cerebellopontine (CP) angle cistern with intraoperative recordings of auditory nerve compound action potentials (CAPs) to ensure highly reproducible results. Rats were killed between day 0 and day 14 after compression and apoptosis of SGCs was evaluated quantitatively as well as qualitatively by terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining, anti-activated caspase-3 immunostaining, Hoechst 33342 staining, and electron microscopy. The average number of TUNEL-positive apoptotic SGCs in each cochlear turn increased from day 1 to day 5 and then decreased gradually to an undetectable level on day 14 after compression. The average proportion of apoptotic SGCs identified in any cochlear turn on any day was always lower than 10%. The results of our present study should be useful in determining the therapeutic time window for rescuing auditory neurons undergoing apoptosis due to injury during surgery in the CP angle.

Nimodipine ameliorates trauma-induced cochlear neuronal death.

Excessive entry of Ca2+ into injured cochlear neurons activates various Ca(2+)-activated enzymes and subsequent spiral ganglion cell death. Therefore, preventing intracellular calcium overload by using Ca2+ channel antagonists may become an important countermeasure to spiral ganglion cell death. We experimentally investigated whether an L-type Ca2+ channel blocker (nimodipine) can rescue traumatized cochlear neurons from degeneration. A group of rats (n = 6) was pre-operatively treated with nimodipine for one week and compression injury was applied to the cerebellopontine angle portion of the cochlear nerve in a highly quantitative fashion. The rats from the compression with nimodipine treatment groups were post-operatively treated with nimodipine for 10 days and killed for histological examination. The histological analysis of the temporal bones revealed that the spiral ganglion cells in the basal turn of the cochlea where the magnitude of traumatic impact had been the least in our experimental condition were rescued in a statistically significant fashion in the compression with nimodipine treatment group. The results of the present study indicate that nimodipine may become an intra- and post-operative important adjunct to raise the rate of hearing preservation in vestibular schwannoma excision or other cerebellopontine angle surgical interventions.

Temporal pattern of cochlear nerve degeneration following compression injury: a quantitative experimental observation.

OBJECT: It has been empirically recognized that the cochlear nerve is highly vulnerable to traumatic stress resulting from surgical procedures; therefore, careful manipulation of the cochlear nerve is mandatory in preventing trauma-induced hearing loss during cerebellopontine angle (CPA) surgery. There is, however, no precise knowledge about the temporal pattern of cochlear nerve degeneration following trauma. This study was performed to determine the temporal pattern of injury that occurs after cochlear nerve trauma, knowledge of which is indispensable not only to neurosurgeons but also to all those who manage lesions involving the cochlear nerve. METHODS: Right suboccipital craniectomies were performed in groups of rats with the aid of a surgical microscope, and the seventh and eighth cranial nerve trunks were identified at the internal auditory meatus. The cochlear nerve was quantifiably compressed while compound action potentials of the cochlear nerve were monitored and recorded. Following injury, one group of rats was killed for histological examination at the end of each week for 4 weeks. Data from this study disclosed that the degeneration of the compressed cochlear nerve progressed in a relatively rapid manner and was complete within 1 week after the insult. The main pathophysiological mechanisms responsible for cochlear neuronal death in this experimental setting appeared to be necrosis, and an apoptotic mechanism seemed to play a subsidiary role. CONCLUSIONS: Accurate knowledge about the temporal profile of trauma-induced cochlear nerve degeneration is closely linked with the problem of the therapeutic time window. The results of the present study indicated that any measures to ameliorate cochlear nerve degeneration following trauma should be started as early as possible (within 1 week) after an injury.

Axonal injury in auditory nerve observed in reversible latency changes of brainstem auditory evoked potentials (BAEP) during cerebellopontine angle manipulations in rats.

Intraoperative monitoring of brainstem auditory evoked potentials (BAEP) has been widely utilized to reduce the incidence of postoperative hearing disturbance due to cerebellopontine angle manipulations. The prolongation of wave V of BAEP is usually used as a criterion to warn the surgeons to modify their surgical maneuvers. However, it is not known whether all neuropathological changes are avoided if BAEP latency intraoperatively returns to the baseline level or some neuropathological changes 'silently' occur even if BAEP normalizes. The aim of this study was to experimentally clarify this point that would be important for the long-term prognosis of patients' hearing. The cerebellopontine angle portion of the auditory nerve was quantitatively compressed in the rats and reversible prolongation of BAEP latency was reproduced just as it occurs during surgery in humans. Twenty-four hours after the compression, the auditory nerve was removed for beta-APP immunostaining to investigate the degree of axonal injury. The results of the present study disclosed that axonal injury occurred even in the cases where the intraoperative normalization of prolonged wave IV (equivalent to wave V in humans) latency had been obtained. Therefore, the interpretation of BAEP changes based only on the prolongation of the latency of BAEP was not enough to prevent the auditory nerve from developing morphological changes. Changes in the amplitude of wave V of BAEP appears to be more sensitive than its latency change as an intraoperative indicator for axonal injury in the auditory nerve.

Subarachnoid hemorrhage caused by a dissecting aneurysm of the internal carotid artery.

OBJECT: Subarachnoid hemorrhage (SAH) caused by the rupture of a dissecting aneurysm of the internal carotid artery (ICA) has been considered rare. Based on data from cooperatively collected cases, the clinical features of patients with dissecting aneurysms of the ICA who presented with SAH were examined. METHODS: Data from 18 patients with dissecting aneurysms of the ICA who presented with SAH diagnosed on the basis of clinical signs, neuroradiological findings, and intraoperative findings from 41 institutions were collected during a 5-year period between 1995 and 1999. The authors found that 0.3% of all cases of SAH and 3.1% of cases of SAH of unverified cause were attributable to a dissecting aneurysm of the ICA. Eleven patients (61%) were middle-aged women, and eight patients (44%) had hypertension. Rebleeding before admission was demonstrated in 13 patients (72%), and intraoperative bleeding was exhibited in half of the patients who underwent surgery during the acute stage. Postoperative growth of an aneurysm bulge or recurrent SAH was seen in five of 10 patients who had undergone wrapping or clipping of the aneurysm bulge in the acute phase. Trapping with or without bypass, which resulted in no postoperative recurrence, was performed in three patients in the acute stage and in two patients in the chronic stage. Twelve patients (67%) had a poor prognosis, primarily attributed to intraoperative bleeding and postoperative recurrence. CONCLUSIONS: Generally, dissecting aneurysms of the ICA are not thought of as frequent causes of SAH. Nonetheless. the presence of these aneurysms should be considered when dealing with SAH because they have a susceptibility to bleeding that can lead to a poor prognosis. Careful surgical planning is necessary to decrease intraoperative bleeding and to avoid postoperative recurrence.

Pineal region tumor manifesting initially as hearing impairment.

An 18-year-old male presented with a pineal region germinoma with hearing impairment as the chief complaint. Magnetic resonance image demonstrated a well-enhanced multi-cystic tumor extending into the upper fourth ventricle and wall of the bilateral lateral ventricles. Audiometry revealed bilateral mild hearing impairment in the low frequencies. Auditory brainstem response recording showed low amplitudes in all waves (IV-V/I ratio < 1) with prolong latencies (I-V and III-V) on the right but no discernable wave at 60 dB clicks on left. Hearing impairment and audiometric findings were improved after ventriculoperitoneal shunt operation. The hearing impairment appeared to be a mixed (conductive and sensorineural) type. The tumor was responsible for the sensorineural deafness because of invasion and compression of the central auditory structures. The inferior brachium was maximally compressed anterolaterally by the dilated bilateral lateral ventricles and posteromedially by the tumor. Hydrocephalus caused conductive deafness by halting or arresting the footplate of stapes movement, as a consequence of high-pressure transmission through the cochlear aqueduct.

[Successful treatment of a huge meningeal hemangiopericytoma using Preoperative Autologous Transfusion and Hemodilutional Autologous Transfusion: case report].

We report successful operations for a meningeal hemangiopericytoma using sufficient amounts of Preoperative Autologous Transfusion (PAT) and Hemodilutional Autologous Transfusion (HAT). A 23-year-old woman with amenorrhea and bilateral visual field disturbance was found to have a huge intracranial tumor. MRI showed a well-enhanced cystic mass in the left middle fossa, suprasellar, intrasellar, sphenoidal sinus, and cavernous sinus. Preoperatively, the tumor was thought to be a cystic pituitary tumor or meningioma. Surgical removal was planned in three steps. The first operation was carried out via the transsphenoidal approach. Total blood loss was 1348 ml and 2 MAP infusion were required to control bleeding. Histopathological diagnosis was hemangiopericytoma. After preparation of PAT 400 ml and HAT 800 ml, we carried out the second partial removal operation mainly via the interhemispheric approach. Total blood loss was 1829 ml and required autologous transfusion only. After preparation of PAT 1200 ml and HAT 400 ml, the last total removal operation was carried out mainly via the pterional and subtemporal approach. Total blood loss was 1813 ml and required autologous transfusion only. We needed 2 MAP infusion in the first operation, but were able to perform total removal successfully without homologous blood transfusion because a sufficient amount of PAT and HAT had been prepared preoperatively. Hemangiopericytoma required postoperative radiation therapy to avoid local recurrence. After successful removal of the tumor surgically, postoperative radiation therapy was able to be carried out efficiently.

Meningiomas with brain edema: radiological characteristics on MRI and review of the literature.

OBJECT: Despite their benign characteristics, meningiomas are often accompanied by perifocal brain edema. The aims of this study are to determine what kind of characteristics on magnetic resonance (MR) image are indicative of a meningioma that produces brain edema and to investigate the mechanism responsible for brain edema accompanying meningiomas. METHODS: Fifty-one patients with meningioma were examined by magnetic resonance imaging (MRI), and tumor size, tumor location, shape of tumor margin, peritumoral rim, and signal intensity of tumor on T2-weighted image (T2WI) were compared and correlated with the presence versus absence of brain edema. Surgical histopathology was also examined and correlated with the MRI findings and brain edema. RESULTS: Shape of tumor margin, peritumoral rim, and signal intensity of tumor on T2WI correlated with brain edema on multivariate analyses. CONCLUSION: Invasive pattern of brain-tumor interface and hyperintensity on T2WI were indicative factors of meningiomas producing brain edema.

A case of macroprolactinoma with subclinical growth hormone production.

We describe a rare case of macroprolactinoma with subclinically synchronous growth hormone (GH) production. A 59-year-old man with a giant adenoma in his pituitary had elevated serum prolactin (PRL) and insulin-like growth factor (IGF)-I levels, despite normal levels of basal GH. Serum GH levels were paradoxically increased in response to an intravenous administration of thyrotropin-releasing hormone (TRH). Prolonged exposure to glucose as a result of oral glucose tolerance testing (oGTT) failed to decrease GH levels. Two-week treatment with cabergoline, a dopamine D2 receptor agonist, decreased serum PRL and GH levels, and size of the tumor. Immunohistochemistry and in situ hybridization revealed PRL-producing cells capable of synchronous GH production. Acidophilic stem cell adenoma may be responsible for these phenomena. The nature of high proliferation and invasive tumor growth should be kept in mind when managing patients with this cell type of adenoma. IGF-I levels should be followed in PRLoma, even when basal GH levels are within the normal range, because mixed PRL- and GH-producing tumors would lie underneath. Further endocrinological examinations such as TRH test and oGTT are recommended when elevated IGF-I levels are detected.