Attenuation of inflammatory and neuropathic pain behaviors in mice through activation of free fatty acid receptor GPR40.

BACKGROUND: The G-protein-coupled receptor 40 (GPR40) is suggested to function as a transmembrane receptor for medium- to long-chain free fatty acids and is implicated to play a role in free fatty acids-mediated enhancement of glucose-stimulated insulin secretion from pancreas. However, the functional role of GPR40 in nervous system including somatosensory pain signaling has not been fully examined yet. RESULTS: Intrathecal injection of GPR40 agonist (MEDICA16 or GW9508) dose-dependently reduced ipsilateral mechanical allodynia in CFA and SNL models and thermal hyperalgesia in carrageenan model. These anti-allodynic and anti-hyperalgesic effects were almost completely reversed by a GPR40 antagonist, GW1100. Immunohistochemical analysis revealed that GPR40 is expressed in spinal dorsal horn and dorsal root ganglion neurons, and immunoblot analysis showed that carrageenan or CFA inflammation or spinal nerve injury resulted in increased expression of GPR40 in these areas. Patch-clamp recordings from spinal cord slices exhibited that bath-application of either MEDICA16 or GW9508 significantly decreased the frequency of spontaneous excitatory postsynaptic currents in the substantia gelatinosa neurons of the three pain models. CONCLUSIONS: Our results indicate that GPR40 signaling pathway plays an important suppressive role in spinal nociceptive processing after inflammation or nerve injury, and that GPR40 agonists might serve as a new class of analgesics for treating inflammatory and neuropathic pain.

Effect of Revascularization on Headache Associated with Moyamoya Disease in Pediatric Patients.

Episodic headache is common in childhood moyamoya disease (MMD). The onset, mechanism, cause of headache and the effect of revascularization surgery on headache are not yet clear. We studied 10 cases of children (7 boys and 3 girls) younger than 18 years who underwent revascularization for MMD between 2009 and 2013. We evaluated frequency of headache and cerebral blood flow changes by single photon emission computed tomography brain imaging with [I123]-labeled iofetamine (IMP-SPECT) before and after surgery. Patients' ages ranged from 0 to 15 years at onset and 2 to 17 years at the time of surgery, mean age being 6.7 and 8.0 years respectively. 9 of 10 patients presented with ischemic symptoms and 8 had headache. 5 patients underwent indirect bypass and 5 underwent combined direct and indirect bypass. Cerebral blood flow improvement was obtained in 14 of the 15 cerebral hemispheres revascularized. The mean follow-up duration was 32.9 months. All the patients had good outcomes with improvement of ischemic neurological deficits. Headache improved in 7 (87.5%) of 8 patients. Headache in pediatric moyamoya disease is associated with change in cerebral hemodynamics. Revascularization including combined direct bypass and indirect techniques may be required to reduce headache in patients with MMD.

Solitary Cranial Langerhans Cell Histiocytosis: Two case reports.

Langerhans cell histiocytosis (LCH) is a proliferation of Langerhans cells intermixed with inflammatory cells, in particular eosinophils, that may manifest as a unisystem (unifocal or multifocal) or multisystem disease. We describe the clinical and histologic spectrum of LCH of the orbit and skull in our two cases. Both cases had unifocal erosive skull lesions with a history of trauma. Typical histologic features included numerous histiocytes with varying degrees of giant cell formation and scattered eosinophilic granulocytes. The presence of Langerhans cells was confirmed by CD1a and S100 immunohistochemistry. LCH has an excellent prognosis when treated with surgical resection, steroids and radiotherapy or chemotherapy. One of our patients is disease free at 7 year follow-up and one patient had regression of lesion on follow-up.

Neuroimaging diagnosis of pineal region tumors-quest for pathognomonic finding of germinoma.

INTRODUCTION: Our study aimed to elucidate the imaging features for the differentiation of pineal germinoma and other pineal region tumors. METHODS: Image data sets of computed tomographic (CT) scan and magnetic resonance imaging (MRI) data of 93 pineal region tumors including 33 germinomas, 30 nongerminomatous germ cell tumors (NGGCTs), 20 pineal parenchymal tumors (PPTs), and 10 miscellaneous tumors of pineal region were reviewed. Imaging features on CT and MRI were qualitatively assessed by three readers. To know the reasons for morphological differences between germinomas and NGGCTs, histological investigation was done. RESULTS: Localized calcification was seen in more than 70 % of germ cells tumors (GCTs: germinomas and NGGCTs) while it was scattered in more than half of PPTs. Cystic components in tumors were most frequent in NGGCTs (62 %). Multiplicity of lesion was restricted to GCTs: 39.4 % in germinoma and 10.0 % in NGGCTs. Thick peritumoral edema was more frequent in germinoma than in NGGCT: 40.6 vs. 14.8 % (p=0.0433, Fisher's test). Bithalamic extension of tumor was seen in 78.8 % of germinomas. It was significantly rare in other groups of tumors (p<0.0001, Fisher's test). The relative collagen amount per unit area was significantly lower in germinoma than in NGGCTs. CONCLUSION: By paying attention to characteristic features as bithalamic extension, thick peritumoral edema, calcification pattern, multiplicity, and their combination, the preoperative differential diagnosis of pineal germinoma will become more accurate.

Transsphenoidal surgical treatment of pituitary adenomas in patients aged 80 years or older.

To know the clinical characteristics of pituitary adenomas in the elderly patients aged 80 years or older who were surgically treated. From 1995 through 2012, 907 patients underwent surgery for the pituitary adenomas at Kagoshima- and Hiroshima University hospitals in Japan. Ten (1.1%) patients were aged 80 years or older. We retrospectively assessed the clinical characteristics including preoperative comorbidities, manifestations, neuroimaging findings, and endocrinologic features of these ten patients. The subjects included eight males and two females. Their ages ranged from 80 to 86 with mean of 83.1 years. Of these, besides one case of growth hormone-producing adenoma, others were clinically nonfunctioning adenoma. Six patients had modest comorbidities such as hypertension, cardiovascular diseases, diabetes mellitus, or chronic kidney dysfunction, and all patients were classified into grade 2-3 on American Society of Anesthesiologists' Physical Status grading. Transsphenoidal surgery was performed in all due to visual disturbance in eight, diabetes mellitus as an intercurrent illness of acromegaly in one, and for the purpose of preventing visual disturbance in one patient who had an adenoma impinging optic chiasm but still had normal visual field. The surgeries provided sufficient decompression of the optic pathways and improved visual disorder in all. In an acromegalic male, his comorbidities considerably improved. No permanent surgical morbidity ensued. More than three axes of anterior pituitary hormones were preoperatively impaired in all, which were rarely recovered. Transsphenoidal surgery is safe and efficient treatment way for patients aged 80 years or older with pituitary adenomas with chiasmatic symptoms when the patients' general condition is well preserved and pituitary hormonal deficiency is adequately replaced.

Factors Affecting the Outcome after Surgical Clipping of Ruptured Distal Anterior Cerebral Artery (DACA) Aneurysms.

Objective The purpose of this study is to assess demographic, clinical, and unique morphological characteristics of distal anterior cerebral artery (DACA) aneurysm. The relation of outcome included Glasgow Outcome Scale (GOS) using various independent variables, Hunt and Hess clinical grade (H&H), Miller Fischer grade, intraoperative rupture, and comparison of outcomes at discharge and last follow-up. Methods Demographic data, aneurysm characteristics, and treatment outcomes were evaluated in 28 ruptured DACA aneurysms operated over a period of 13 years. Association between independent variables and dependent variables (GOS) at discharge and at last follow-up (13 years) was analyzed, and the interrelationship between these factors and outcome was evaluated. GOS was used to assess functional outcomes. Results Over a period of 13 years, 500 patients harboring ruptured intracranial aneurysms were surgically clipped, and out of them 28 patients (5.6%) had ruptured DACA aneurysms. In this series, 20 (71.4%) patients had low grade and 8 (28.6%) had high grade H&H. Out of the 28 patients, 19 (67.8%) had good recovery, 6 (21.5%) were severely disabled, and 3 (10.7%) died at the time of discharge. On the last follow-up (13 years), smoking ( p -value 0.03) and use of temporary clip ( p -value 0.00) were significant predictors for unfavorable outcome. Conclusion The results of our case series show that even with ruptured aneurysm excellent overall outcome after microsurgical clipping can be achieved, even though among cerebral aneurysms, DACA aneurysm is considered to have less favorable outcome. Alcohol consumption and use of temporary clip were the predictors for unfavorable outcome at the time of discharge. On the last follow-up, smoking and use of temporary clip were found to be the risk factors for unfavorable outcome. Although the small sample size of this study is a limitation, smoking and use of temporary clip play an important role on the overall outcome. The aim of this study was to analyze data to determine factors which may influence outcome after surgical clipping of ruptured DACA aneurysms.

Changes in Electrocardiogram in Patients With Spontaneous Subarachnoid Hemorrhage: A Cross-Sectional Study.

Background Electrocardiographic (ECG) changes are frequently reported findings in patients with subarachnoid hemorrhage (SAH). We conducted a retrospective descriptive study to assess the prevalence of electrocardiographic changes in patients with non-traumatic SAH.  Methods In this single-center retrospective cross-sectional study, ECG recordings of 45 patients who presented to Tribhuvan University Teaching Hospital in the year 2019 with SAH were collected and analyzed to detect any abnormalities.  Results In our study, 88.8% of patients had some form of ECG abnormality. The most common ECG abnormalities associated with SAH were QTc prolongation, T-wave abnormalities, and bradycardia, which were found, respectively, in 35.5%, 24.4%, and 24.4% of the patients. Other ECG changes we observed include ST depression, large U-waves, atrial fibrillation, and premature ventricular contractions. Conclusion Morphological and rhythm abnormalities are frequently observed in patients with SAH, which may cause diagnostic dilemmas and unnecessary workups. Further studies are required to evaluate their significance and correlate ECG changes with clinical outcomes.

Bilateral Internal Carotid Arteries Occlusion: A Case Report.

Bilateral internal carotid artery occlusion is a disease that is encountered rarely. We report a case of a 54 years old female smoker, who presented with acute onset right-sided limb weakness, facial deviation and slurring of speech. On computed tomography angiography occlusion of the bilateral internal carotid artery was seen and a high-flow collateral circulation was formed through the vertebrobasilar system. Computed tomography brain perfusion showed marked cerebral hypoperfusion on the left side. The patient was thrombolysed and kept on dual antiplatelet therapy. Post-medical treatment, motor power and speech significantly improved.

Outcome of Decompressive Craniectomy for Traumatic Brain Injury: An Institutional-Based Analysis from Nepal.

OBJECTIVE: Decompressive craniectomy (DC) is one of the commonly used treatment modalities for refractory intracranial hypertension after traumatic brain injury. The objective of this study is to assess the functional outcome following DC in closed traumatic brain injury based on Glasgow Outcome Scale (GOS). MATERIALS AND METHODS: This is a retrospective study conducted at Nepal Mediciti Hospital, Nepal, from September 2017 to October 2019. Data of the patients who had undergone DC for closed traumatic brain injury were reviewed from medical record files. Patients who had DC for nontraumatic causes were excluded from the study. Functional outcome was assessed using GOS at 3 months of follow-up. RESULTS: Of the 52 decompressive craniectomies, 46 were included in the study. The majority was male (71.7%). The mean age and the mean Glasgow Coma Scale (GCS) score at presentation were 41.87 (standard deviation [SD] ± 15.29) and 7.59 (SD ± 2.97), respectively. The most common mode of injury was road traffic accident (76.1%). 60.9% had GCS score ≤8 while 39.1% had >8 GCS on admission. 34.8% had both the pupils reactive while 58.7% were anisocoric. Majority had Marshall IV and above grade of injury (67.4%). Sixteen (34.8%) had inhospital mortality. Favorable outcome was seen in 39.1%. GCS score >8 at presentation (72.2%, P < 0.001), bilaterally intact pupillary reflexes (75%, P < 0.001), Marshall grade injury ≤3 on computed tomography scan (90%, P < 0.001), and age <50 years (50%, P = 0.039) were significantly associated with favorable outcome. Procedure-related complications were seen in 36.9%. CONCLUSION: Favorable outcome was seen in 39.1%. Age <50 years, higher GCS score at presentation (>8), intact pupillary reflexes, and lower Marshall grade injuries were associated with favorable outcome. We recommend a larger prospective study to assess the long-term functional outcome after DC using extended GOS.

Retrospective Study and Outcome Predictor after Microsurgical Resection of Cerebral Arteriovenous Malformations in Nepal.

OBJECTIVE: The purpose of this study is to assess demographic, clinical, and morphological characteristics of patients with brain arteriovenous malformations (bAVMs). The relation of outcome using modified Ranklin Scale (mRS) at time of discharge, early and last follow ups with respect to various factors. MATERIALS AND METHODS: Demographic data, arteriovenous malformation characteristics, and treatment outcomes were evaluated in 43 bAVMs treated with microsurgery between 2009 and 2019. For this series, 43 patients were retrospectively reviewed. A subgroup analysis for Spetzler-Martin grades (SMG) I/II, III, IV/V and III-V were performed. The mRS was used to assess functional outcomes. RESULTS: Overall, mean age at diagnosis was 33 years (standard deviation = 19). Transient deficit, mRS deterioration and impaired functional outcome occurred less frequently in SMG I-II patients compared with Grade III-V patients combined (29% vs. 32% respectively, P = 0.00). All patients with SMG Grade I, Supplemented SMG Grade 2, 3, 4 and 6 had a mRS score of 2 or less at the last follow-up. Age was the only significant predictor of overall outcome after bAVM surgery on Chi-square test (P = 0.046), i.e: all patients <20 years had mRS score of 2 or less on last follow-up. Unfavorable outcome (mRS score of 3 or more than 3) level increased with higher grades in SMG on long term follow-up. CONCLUSION: The results of our case series of bAVM with SMG Grade I and Suplemented Grade 2, 3, 4 and even higher grade i.e., 6 can have excellent overall outcome after microsurgical resection. Association of factors which increases the grading system of bAVM like eloquence, deep venous drainage and increasing sizes did not correlate with the predicted unfavorable outcomes, whereas age of patients was a predictor of overall outcome. Although the small sample size of this study is a limitation, age of patient plays important role on the overall outcome.

Microvascular Decompression in Patients Aged 30 Years or Younger.

OBJECTIVE: The aim of this study was to identify the etiology of hemifacial spasm (HFS) and trigeminal neuralgia (TN) in patients aged 30 years or younger and to examine the efficacy of microvascular decompression (MVD). PATIENTS AND METHODS: Between 1996 and 2012, 228 HFS and 190 TN patients underwent MVD at Atsuchi Neurosurgical Hospital. Of these, 7 patients were 30 years of age or younger at the time of treatment (HFS: n = 6, TN: n = 1). Assessments were based on their medical history and on magnetic resonance imaging, magnetic resonance angiography, surgical, and follow-up findings. RESULTS: The age of the 6 HFS patients ranged from 23 to 30 years (mean 27.8 ± 1.8 [standard deviation] years) at the time of surgery; the earliest symptom onset was in an 11-year-old boy. We noted vascular variations in 5 patients, a duplicate posterior inferior cerebellar artery in 2 patients, a short basilar artery in 1 patient, and an aberrant arterial course in 2 patients. At the latest follow-up, 1-69 months after MVD, 5 of the HFS patients were asymptomatic and the 6th had mild residual symptoms. A 23-year-old TN female underwent straightening of the trigeminal nerve by separation of a thickened arachnoid membrane from the nerve and dislocation of a small branch of the superior cerebellar artery from the distal end of the root exit zone. While she continued to experience occasional facial pain 48 months after the operation, she required no medication because surgery yielded significant pain amelioration. CONCLUSION: Although the pathogenesis of early-onset HFS and TN remains unclear, our findings suggest that vascular variations may be related to the etiology of vascular compression symptoms in patients with HFS or TN. MVD was useful for the treatment of neurovascular compression symptoms in young patients.

Choroid Plexus Tumors: Experience of 10 Cases with Special References to Adult Cases.

Choroid plexus tumors (CPTs) are rare intraventricular neoplasms accounting for about 0.3-0.6% of all intracranial tumors. This retrospective study on CPTs presents clinico-pathological features and management strategies based on a 20-year single-institutional experience. This series included 10 consecutive patients with pathologically proven CPTs; 5 choroid plexus papillomas (CPPs), 3 atypical CPPs (ACPPs), and 2 choroid plexus carcinomas (CPCs). Their clinical, radiological, and histopathological features as well as management including follow-up studies were reviewed. The patients included five males and five females, aging from 0 years to 61 years with median of 28 years. The affected site was lateral ventricle in two adults and fourth ventricle in eight patients; four children and four adults. The most common symptoms were gait disturbance and memory disturbance. All the patients underwent craniotomy with total, subtotal, and partial removals achieved in 50%, 40%, and 10% of the patients, respectively. The occurrence of the high grade subtypes was 50% in both the adult and pediatric groups. The Ki-67/MIB-1 index increased across the three histological subtypes, from CPP to ACPP and then to CPC. Adjuvant therapy was administered in three patients. The two patients (one adult and one child) with CPC died of whole central nervous system dissemination. At a median of 62-month follow-up, the other eight patients were alive, with only one patient having recurrence and reoperation. The results demonstrate that gross total resection is usually curative for CPP and ACPP, and adjuvant chemoradiotherapy would be required for CPC and incompletely resected ACPP.

Third ventricular atypical meningioma which recurred with further malignant progression.

Meningiomas in the third ventricle are rare, with only very few cases reported in the literature. We report a case of primary third ventricular anaplastic meningioma in a 49-year-old man who presented with progressive weakness of the left limbs and headache. Magnetic resonance imaging revealed a tumor which seemed to arise from the right thalamus and extending into third ventricle. The tumor was heterogeneously enhanced with gadolinium. It was totally removed by right transventricular-subchoroidal approach. The lesion was intraoperatively found to be whitish hard and embedded in right thalamus, but had attachment to choroid plexus near foramen Monroi with narrow interface. The histological diagnosis was atypical meningioma, WHO Grade II. Lesion recurred 20 months later and was resected via the same approach, which turned out to be papillary meningioma, WHO Grade III. The patient had second recurrence 23 months after second surgery which was operated and the final diagnosis was anaplastic meningioma (WHO Grade III). Literature review showed meningioma of the third ventricle is quite exceptional and more than half of the cases were aggressive subtypes (Grade II or III).

Mature posterior fossa teratoma mimicking dermoid cyst.

We describe a very rare case of mature posterior fossa teratoma in an adult who presented with clinico-radiological findings consistent with a dermoid cyst. A computed tomography scan showed a hypodense mass in the cistern magna with calcification and a sinus tract in the occipital bone. Magnetic resonance imaging revealed a hypo- to hyperintense mass without contrast enhancement. The intraoperative picture showed a dermal sinus and a cyst containing lipid, keratin and hair. Histopathological examination showed a tumor with components of all the three germ layers; thereby, a diagnosis of mature teratoma was made. The histopathological differentiation between teratoma and dermoid cyst is very valuable for ruling out the presence of immature/malignant or germinomatous components that would require further adjuvant therapies. Thus, we here present a rare case of posterior fossa teratoma mimicking dermoid cyst and emphasize the importance of histopathological differentiation between these entities.

Immunohistochemical expression of thrombomodulin in vestibular schwannoma.

Many vestibular schwannomas (VS) manifest intratumoral microhemorrhages whose underlying mechanisms are not fully understood. Thrombomodulin (TM) is an endothelial anticoagulant cofactor that promotes the thrombin-mediated formation of activated protein C that inhibits thrombus formation. We investigated the existence of TM in VS and its potential role in the development of microhemorrhages. We used immunohistochemical staining to study the expression of TM in tissues derived from 25 patients with VS. Hemosiderin deposition was examined by Berlin blue staining and compared with the expression of TM. Vascular endothelial cells in all 25 VS tissues expressed TM. The TM-positive vessel ratio, calculated by dividing the number of TM-positive by the number of CD34-positive lumens, was significantly higher in hemosiderin-laden than hemosiderin-negative tissues (0.71 ± 0.17 vs. 0.53 ± 0.31, p = 0.049, Mann-Whitney U test). Our findings suggest a close relationship between the expression of TM and microhemorrhage in VS.

Cerebellopontine angle endodermal cyst presenting with hemifacial spasm.

Intracranial endodermal cysts presenting with hemifacial spasm (HFS) are extremely rare. We report a right cerebellopontine angle (CPA) endodermal cyst in a 56-year-old man who presented with a 6-month history of right-sided hemifacial spasm. Computed tomography revealed a homogenous, well-demarcated, hyperdense lesion extending from prepontine cistern to right CPA. Magnetic resonance imaging demonstrated a right CPA extra-axial cystic lesion protruding into Meckel's cave, with compression of cranial nerves VII and VIII. Light brown, creamy cystic content was totally removed, and the thin cyst wall surrounding cranial nerves VII and VIII and the right vertebral artery was subtotally removed through the right lateral suboccipital approach. On microscopic examination, the cyst wall was composed of mono- to multilayered stratified epithelia, which were lined by ciliated or nonciliated cuboidal cells, with cilia showing the characteristic 9 + 2 pattern. Immunohistochemistry showed positive staining of cells composing the cyst wall with carcinoembryonic antigen, epithelial membrane antigen, cytokeratin 8, and negative staining with cytokeratin 20, and S-100, thereby characterizing endodermal cyst. Postoperatively, the patient was free of facial spasm.