Features of psychological reactions induced by perampanel: A case report.

WHAT IS KNOWN AND OBJECTIVE: Perampanel, an anticonvulsant, might induce psychological reactions. CASE DESCRIPTION: A 70-year-old woman, who had been taking 2500 mg/day levetiracetam, complained of right-hand minor-convulsion. Perampanel of 2 mg/day was additionally prescribed, and the dosage was increased to 4 mg/day. Two weeks after taking 4 mg/day perampanel, she changed her personality and kept insulting her husband; however, the patient herself was aware of her strange behaviour. She regained her normal personality after quitting the perampanel medication. WHAT IS NEW AND CONCLUSION: This self-awareness is crucial to distinguish the perampanel-induced reaction from psychosis.

Headache in patients with chronic subdural hematoma: analysis in 1080 patients.

Headache is a major symptom in chronic subdural hematoma (CSDH) patients. However, some CSDH patients do not complain headache although the hematoma is thick with definite midline shift. This clinical study was performed to identify the mechanism of headache in CSDH patients. We compiled clinical data of 1080 surgically treated CSDH patients (711 males and 369 females), and in 54 cases, the pressure of hematoma was measured during burr hole surgery using a glass-stick manometer. Headache was recognized in 22.6% of patients, while nausea or vomit suggesting increased intracranial pressure was detected in only 3.0%. Ophthalmological examination was performed in 238 patients, and papilledema was identified in only one patient (0.4%). The mean age of patients with headache (59.8 ± 16.9 years) was significantly younger than that of those without (75.7 ± 11.2 years) (P < 0.01). In 54 cases, the mean hematoma pressure was not significantly different between patients with (17.1 ± 6.2 mmH2O) and without (18.4 ± 7.2 mmH2O) headache (P > 0.10). Hematoma thickness was significantly greater in patients without headache (P < 0.01), but the ratio of midline shift to hematoma thickness was significantly greater in patients with headache (P < 0.01). In our results, the status of increased intracranial pressure was rare in CSDH patients, and high hematoma pressure was not a cause of headache. Midline shift was the most influenced factor for headache in our study, and based on the results, the authors consider that the potential cause of headache in CSDH might be stretching or twisting of the pain-sensitive meninges and meningeal arteries or veins.

Delayed post-traumatic large subgaleal hematoma caused by diastasis of rhomboid skull suture on the transverse sinus.

PURPOSE: This study aimed to consider an appropriate treatment for large subgaleal hematoma with skull fracture and epidural hematoma (EDH). CASE REPORT: A 6-year-old boy presented at our hospital with head trauma, and computed tomography (CT) showed a thin EDH in the right temporo-occipital area and cranial diastasis in the right lambdoidal suture. However, no neurological deficits were identified in the patient. One week after trauma, he visited our hospital again with a massive fluctuant watery mass extending from the forehead to the right temporoparietal areas, and laboratory data revealed that he was anemic. CT showed a massive subgaleal hematoma with extremely high density around the cranial diastasis. Damage of the transverse sinus was suspected, and emergent sinus repair surgery was performed. The surgery disclosed that bleeding from the transverse sinus was flowing out extracranially through the cranial diastasis. The subgaleal and epidural hematomas were removed, and bleeding from the sinus was stopped by dural tacking sutures along the transverse sinus. Postoperative CT demonstrated complete disappearance of epidural and subgaleal hematomas. The patient recovered from general fatigue without blood transfusion and was discharged 9 days after surgery. CONCLUSIONS: The therapeutic strategy for massive subgaleal hematoma is individualized. However, treatment for massive subgaleal hematoma with skull fracture should not be considered the same as for hematoma without skull fracture. Emergent surgery is recommended before neurological deterioration is recognized in the patient if damage to the dural sinus is suspected.

Radiation-induced meningiomas in multiple regions, showing rapid recurrence and a high MIB 1 labeling index: a case report and review of the literature.

Combined chemotherapy and prophylactic cranial irradiation has improved the prognosis of children with acute leukemia. However cranial irradiation carries a latent risk of the induction of secondary intracranial tumors. We encountered a patient who developed multiple intracranial radiation-induced meningiomas (RIMs) 25 years after prophylactic cranial irradiation for the treatment of acute leukemia in childhood. The patient had 3 intracranial lesions, 1 of which showed rapid growth within 6 months; another of the tumors also enlarged within a short period. All of the tumors were surgically treated, and immunohistochemistry indicated a high MIB-1 labeling index in each of the multiple lesions. In the literature, the MIB-1 labeling indices of 27 tumors from 21 patients were examined. Among them, 12 recurrent tumors showed higher MIB-1 labeling indices compared to the MIB-1 labeling indices of the non-recurrent tumors. Overall, 11 of the patients with RIM had multiple lesions and 8 cases developed recurrence (72.7%). RIM cases with multiple lesions had higher MIB-1 labeling indices compared to the MIB-1 labeling indices of cases with single lesions. Collectively, these data showed that the MIB-1 labeling index is as important for predicting RIM recurrences, as it is for predicting sporadic meningioma (SM) recurrences. RIMs should be treated more aggressively than SMs because of their greater malignant potential.

Vertebral artery dissection caused by swinging a golf club: case report and literature review.

Vertebral artery (VA) dissection caused by swinging a golf club is extremely rare, and the mechanism of the dissection has not been elucidated. A 39-year-old man suddenly felt sharp neck pain and dizziness when he swung a driver while playing golf and visited our clinic. Imaging studies showed acute right cerebellar infarction and complete occlusion of the right VA at the C2 (axis) level. After 1 month of 100 mg aspirin treatment, the occluded right VA was completely recanalized and the patient became totally asymptomatic. Professional golfers look at the position of the ball on the ground or tee until completion of their follow-through. However, some amateur golfers look in the direction that the ball travels at the beginning of their follow-through. It is hypothesized that this rapid disproportionate head rotation produces VA elongation and distortion, mainly at the C2 level, causing stenosis or occlusion of the artery.

Molecular status of pituitary carcinoma and atypical adenoma that contributes the effectiveness of temozolomide.

There have been several reports of temozolomide (TMZ) treatment of pituitary carcinomas and atypical adenomas. O(6)-methyl-guanine-DNA methyltransferase is not the sole molecule determining the sensitivity to TMZ in pituitary carcinomas and atypical adenomas. The Japan Society of Hypothalamic and Pituitary Tumors study suggests that MSH6, one of mismatch repair pathway enzyme, fulfills a contributory role to the efficacy of TMZ treatment for pituitary carcinomas and atypical adenomas. The preserved MSH6 function might be essential for the responsiveness to TMZ treatment in pituitary carcinomas and atypical adenomas.

Fulminant Non-occlusive Mesenteric Ischemia After Head Trauma: Report of Two Cases.

There have been no case reports of non-occlusive mesenteric ischemia (NOMI) following head trauma. Our two patients with non-surgical traumatic intracerebral hemorrhage succumbed to NOMI one week after the injury. Both were women over age 80 years and were clinically improving before NOMI occurred. One patient had been eating since admission, while the other had not, which prompted the initiation of enteral nutrition on day 5. The patients shared many characteristics: 1) over age 80 years; 2) minor brain contusion; 3) constipation for a week; 4) minimal abdominal symptoms; 5) rapidly developing leukocytosis, hyperglycemia, hypernatremia, and elevated blood urea nitrogen; 6) massive diarrhea with a small amount of blood on the same day that laboratory data became abnormal; and 7) fever and shock developed shortly after diarrhea appeared. Because of the fulminant worsening of the condition, shock status, and old age, surgical intervention was considered high risk and not performed in either patient. In retrospect, if NOMI had been diagnosed earlier when the acute pancreatitis-like symptoms began, surgical intervention may have saved their lives. Clinicians should be aware that NOMI can occur after relatively minor head trauma, which can cause death if the diagnosis is delayed.

Urinary growth hormone level and insulin-like growth factor-1 standard deviation score (IGF-SDS) can discriminate adult patients with severe growth hormone deficiency.

Adult growth hormone (GH) deficiency (AGHD) in Japan is diagnosed based on peak GH concentrations during GH provocative tests such as GHRP-2 stimulation test. In this study, we aimed to evaluate the ability of serum insulin-like growth factor-1 (sIGF-1) and urinary GH (uGH) at the time of awakening to diagnose AGHD. Fifty-nine patients with pituitary disease (32 men and 27 women; age 20-85 y (57.5 ± 15.5, mean ± SD) underwent GHRP-2 stimulation and sIGF-1 testing. Thirty-six and 23 patients were diagnosed with and without severe AGHD, respectively based on a peak GH response of <9 ng/mL to GHRP-2 stimulation. Serum IGF-1 was evaluated as a standard deviation score (IGF-1 SDS) based on age and sex. We determined whether uGH levels in urine samples from 42 of the 59 patients at awakening were above or below the sensitivity limit. We evaluated IGF-1 SDS and uGH levels in a control group of 15 healthy volunteers. Values for IGF-1 SDS were significantly lower in patients with, than without (-2.07 ± 1.77 vs.-0.03 ± 0.92, mean ± SD; p < 0.001) AGHD whereas the range of IGF-1 SDS substantially overlapped at > -1.4. IGF-1 SDS discriminated AGHD more effectively in patients aged ≤60 years. The χ2 test revealed a statistical relationship between uGH and AGHD (test statistic: 7.0104 ≥ χ2 (1; 0.01) = 6.6349). When IGF-1 SDS is < -1.4 or uGH is below the sensitivity limit, AGHD can be detected with high sensitivity.

Midline Shift Induced by the Drainage of Cerebrospinal Fluid in Three Patients With External Decompression.

It is not rare that progressive hydrocephalus worsens clinical conditions in a patient with external decompression and drainage or shunt surgery is required. However, spinal drainage or shunt surgeries potentially carry a risk of causing paradoxical herniation in a patient with decompressive craniectomy, particularly in a comatose case with wide craniectomy. Careful and strict observations are necessary for such patients. In our three comatose cases with craniectomy, paradoxical herniation occurred due to excessive drainage after 5-7 days of shunt surgery and lumbar drainage, although the drainage pressure was set at more than 10 cmH2O. Fortunately, in the three cases, the herniation improved within a few days after the drain was clamped and the bed was flattened. However, the Trendelenburg position and epidural blood patch might be necessary if paradoxical herniation occurs acutely after lumbar puncture or drainage because delayed resolution can be fatal in the herniation.

A case of reversible posterior leukoencephalopathy syndrome with acute hypotension.

Reversible posterior leukoencephalopathy syndrome (RPLS) is theoretically associated with hypertensive encephalopathy because the most patients demonstrate abrupt increasing of blood pressure (BP). A 59-year-old woman, who had undergone cholecystectomy 4 days before, complained of a headache and rapidly progressing visual disturbance. Her BP was postoperatively controlled at around 150/80, but her BP was 89/46 when she noticed her symptoms. Magnetic resonance imaging showed vasogenic edema in bilateral occipital and right parietal lobes, and intracranial magnetic resonance angiography revealed bilateral diffuse peripheral vasoconstriction. After discontinuing ropivacaine administration via epidural catheter, her BP rose to 114/62 and her symptoms completely disappeared within a few days. Except for hypotension, the clinical course and the radiological evidences in our case were consistent with RPLE. This case supports another hypothesis of RPLS mechanism that arterial endothelial injury by toxic drug effect results in transudation of fluid from blood vessels causing vasogenic brain edema.

A case of subarachnoid hemorrhage with pituitary apoplexy caused by idiopathic hypertrophic pachymeningitis.

Steroid therapy is considered to improve clinical symptoms in hypertrophic pachymeningitis. We present a 70-year-old man with idiopathic hypertrophic pachymeningitis, whose clinical signs progressively worsened despite steroid therapy. He died of subarachnoid hemorrhage (SAH) with pituitary apoplexy 2 months after the admission regardless of improvement of laboratory data and magnetic resonance imaging appearance by one-and-half-month steroid therapy. Autopsy revealed thickened dura mater supporting the diagnosis of hypertrophic pachymeningitis. Brain parenchyma is generally not affected by the disease; however, histological investigation suggested that inflammation of the dura caused damage to superior hypophyseal artery resulting in SAH and apoplexy in the anterior lobe of the pituitary gland. The higher dose and the longer duration of steroid therapy should have achieved in our case although most laboratory data recovered within the normal range. The aggressiveness of hypertrophic pachymeningitis must be evaluated by clinical signs rather than by laboratory data or imaging examinations.

Molecular morphology of pituitary cells, from conventional immunohistochemistry to fluorescein imaging.

In situ hybridization (ISH) at the electron microscopic (EM) level is essential for elucidating the intracellular distribution and role of mRNA in protein synthesis. EM-ISH is considered to be an important tool for clarifying the intracellular localization of mRNA and the exact site of pituitary hormone synthesis on the rough endoplasmic reticulum. A combined ISH and immunohistochemistry (IHC) under EM (EM-ISH&IHC) approach has sufficient ultrastructural resolution, and provides two-dimensional images of the subcellular localization of pituitary hormone and its mRNA in a pituitary cell. The advantages of semiconductor nanocrystals (quantum dots, Qdots) and confocal laser scanning microscopy (CLSM) enable us to obtain three-dimensional images of the subcellular localization of pituitary hormone and its mRNA. Both EM-ISH&IHC and ISH & IHC using Qdots and CLSM are useful for understanding the relationships between protein and mRNA simultaneously in two or three dimensions. CLSM observation of rab3B and SNARE proteins such as SNAP-25 and syntaxin has revealed that both rab3B and SNARE system proteins play important roles and work together as the exocytotic machinery in anterior pituitary cells. Another important issue is the intracellular transport and secretion of pituitary hormone. We have developed an experimental pituitary cell line, GH3 cell, which has growth hormone (GH) linked to enhanced yellow fluorescein protein (EYFP). This stable GH3 cell secretes GH linked to EYFP upon stimulation by Ca²+ influx or Ca²+ release from storage. This GH3 cell line is useful for the real-time visualization of the intracellular transport and secretion of GH. These three methods from conventional immunohistochemistry and fluorescein imaging allow us to consecutively visualize the process of transcription, translation, transport and secretion of anterior pituitary hormone.

Functional molecular morphology of anterior pituitary cells, from hormone production to intracellular transport and secretion.

Combined in situ hybridization (ISH) and immunohistochemistry (IHC) under electron microscopy (EM-ISH & IHC) has sufficient ultrastructural resolution to provide two-dimensional images of subcellular localization of pituitary hormone and its mRNA in a pituitary cell. The advantages of semiconductor nanocrystals (Quantum dots; Qdots) and confocal laser scanning microscopy (CLSM) enable us to obtain three-dimensional images of the subcellular localization of pituitary hormone and its mRNA. Both EM-ISH & IHC and ISH & IHC using Qdots and CLSM are useful for understanding the relationship between protein and mRNA simultaneously in two or three dimensions. CLSM observation of rab3B and SNARE proteins such as SNAP-25 and syntaxin revealed that both rab3B and SNARE system proteins play an important role and work together as the exocytotic machinery in anterior pituitary cells. Another important issue is the intracellular transport and secretion of pituitary hormone. An experimental pituitary cell line, the GH3 cell, in which growth hormone (GH) is linked to enhanced yellow fluorescein protein (EYFP), has been developed. This stable GH3 cell secretes GH linked to EYFP upon being stimulated by Ca(2+) influx or Ca(2+) release from storage. This GH3 cell is useful for real-time visualization of the intracellular transport and secretion of GH. These three methods enable us to visualize consecutively the processes of transcription, translation, transport, and secretion of pituitary hormone.

Clinico-pathological significance of RCAS1 expression in gliomas: a potential mechanism of tumor immune escape.

RCAS1, one of the tumor cell surface antigens, is strongly expressed in aggressive tumors. RCAS1 suppresses the in vitro growth of immune effector cells. We investigated the expression of RCAS1 in 57 gliomas using immunohistochemistry. Furthermore, we examined the association of the RCAS1 expression with the infiltration of tumor infiltrating lymphocyte (TIL). RCAS1 overexpression was significantly correlated with high histological grade and poor prognosis. Reduced infiltration and increased apoptosis of TILs was observed in RCAS1-positive regions. Apoptotsis of TILs appeared to be induced by RCAS1. RCAS1 expression in gliomas may play roles in tumor progression and tumor immune escape.

Pathophysiology of tethered cord syndrome and similar complex disorders.

Tethered cord syndrome (TCS) is a stretch-induced functional disorder of the spinal cord due to the fact that its caudal portion is anchored by an inelastic structure. The functional lesion of TCS is generally situated in the lumbosacral cord, and many authors have shown that the syndrome is reversible via surgery to untether the cord. To clarify the expressions relevant to TCS, such as "cord tethering" and "tethered cord," the authors have formulated three categories. These categories include cases that show the anatomical appearance of spinal cord stretching. Among them, Category 1 is isolated to represent the "true TCS." The authors focus their discussion of the pathophysiology of TCS on Category 1 to explain the impaired oxidative metabolism and electrophysiological derangements within the tethered spinal cord, which is the primary intrinsic cause of the dysfunction. Furthermore, they extend the discussion to the extrinsic (outside the spinal cord) factors and other complex conditions that mimic TCS.

Primary malignant B-cell-type dural lymphoma: Case report.

BACKGROUND: The primary malignant dural lymphoma of B-cell type is rare. Our review of the literature (24 cases) indicated that patients with this tumor had female predominance, immunocompetency, and longer survival compared with those with primary malignant intracerebral lymphomas. Based on its clinicopathological features, this dural lymphoma may be classified differently from other types of malignant lymphomas in the central nervous system. CASE DESCRIPTION: The authors report an example of a patient who had a favorable course of malignant dural lymphoma. A 59-year-old woman presented with primary malignant dural lymphoma in the frontal area. Histological diagnosis was a diffuse large B-cell-type lymphoma of intermediate malignancy, but MIB-1 index was extremely high. Subtotal tumor removal was followed by 4 courses of chemotherapy. Thirty months after surgery, the patient is asymptomatic with no MRI evidence of recurrence. A combination of subtotal resection and chemotherapy for a primary malignant dural lymphoma is an effective means to attempt cure of this tumor. CONCLUSION: These rare tumors may be managed successfully by subtotal resection and postoperative treatment. We believe that chemotherapy is the treatment of choice after subtotal resection of malignant dural lymphomas, as experienced in our case.

Glioblastoma multiforme versus pleomorphic xanthoastrocytoma with anaplastic features in the pathological diagnosis: a case report.

BACKGROUND: Pleomorphic xanthoastrocytoma (PXA) with anaplastic features should be strictly distinguished from glioblastoma multiforme (GBM). CASE PRESENTATION: A case of PXA that was initially diagnosed as GBM is presented. A 42-year-old man visited our clinic because of right hemiparesis and total aphasia. Head magnetic resonance imaging demonstrated enhanced multiple cystic lesions in the left temporal lobe suggesting an intra-parenchymal brain tumor. The lesion was partially removed and GBM with a Ki-67 index of 20 % was diagnosed by pathological examination of the resected specimen. Despite receiving radiation and chemotherapy, the patient died 6 months after the first admission. At autopsy, the boundary between the tumor and normal brain tissue was clear. Large parts of the tumor demonstrated typical features of PXA, including pleomorphism, clear xanthomatous cells with foamy cytoplasm, positive silver staining, and a Ki-67 index of less than 1 %. DISCUSSION AND CONCLUSIONS: GBM should be diagnosed only when the majority of the tumor cells are undifferentiated. Although the operative specimen appeared typical GBM histologically, the diagnosis of GBM was subsequently excluded by the autopsy finding that much of the tumor had the characteristic features of a benign PXA. Therefore, the final diagnosis in this case was PXA with anaplastic features. PXA with anaplastic features should be carefully distinguished from GBM to facilitate appropriate decisions concerning treatment.

Characterization of microglia induced from mouse embryonic stem cells and their migration into the brain parenchyma.

We derived microglia from mouse embryonic stem cells (ES cells) at very high density. Using the markers Mac1(+)/CD45(low) and Mac1(+)/CD45(high) to define microglia and macrophages, respectively, we show that Mac1(+) cells are induced by GM-CSF stimulation following neuronal differentiation of mouse ES cells using a five-step method. CD45(low) expression was high and CD45(high) expression was low on induced cells. We used a density gradient method to obtain a large amount of microglia-like cells, approximately 90% of Mac1(+) cells. Microglia-like cells expressed MHC class I, class II, CD40, CD80, CD86, and IFN-gammaR. The expression level of these molecules on microglia-like cells was barely enhanced by IFN-gamma. Intravenously transferred GFP(+) microglia derived from GFP(+) ES cells selectively accumulated in brain but not in peripheral tissues such as spleen and lymph node. GFP(+) cells were detected mainly in corpus callosum and hippocampus but were rarely seen in cerebral cortex, where Iba1, another marker of microglia, is primarily expressed. Furthermore, both GFP(+) and Iba1(+) cells exhibited a ramified morphology characteristic of mature microglia. These studies suggest that ES cell-derived microglia-like cells obtained using our protocol are functional and migrate selectively into the brain but not into peripheral tissues after intravenous transplantation.

A rapidly enlarging nocardial brain abscess mimicking malignant glioma.

Nocardial brain abscesses are uncommon and are not preceded by clear infectious symptoms in most cases. Delayed identification of the bacteria is responsible for a high mortality rate. A 58-year-old afebrile woman was admitted to our hospital because of progressive right hemiparesis and aphasia. Magnetic resonance imaging (MRI) showed a single ring-enhanced lesion in the left frontal lobe. It was extremely difficult to establish the diagnosis of brain abscess, because the laboratory data provided little evidence of bacterial infection, (201)TlCl-scintigraphy revealed definite accumulation of thallium in the lesion, and follow-up MRI demonstrated rapid enlargement of the lesion. Total resection was performed because of the possibility of a malignant brain tumor, but brain abscess was finally diagnosed with histological examination. A nocardial species was detected through microscopic examination of the pus obtained at surgery, and this precise diagnosis of nocardial brain abscess in the early stage enabled the administration of appropriate antibiotics and the patient's quick recovery. Nocardial brain abscesses are often misdiagnosed as malignant brain tumors, and a definitive diagnosis may not be possible without detecting bacteria from the lesion. Total excision of the abscess can produce good results when the abscess is large and located superficially, but incomplete aspiration and drainage of a lesion is associated with a high chance of relapse.