Brainstem cavernous hemangioma with improvement of Holmes tremor on excision.

An 8-year-old boy presenting with left-angle paralysis, tremor in upper and lower extremities, and diplopia was diagnosed with hemorrhage from a mesencephalic cavernous hemangioma. He underwent hemangiomectomy through the occipital transtentorial approach 4 weeks post-hemorrhage, after which Holmes tremor (HT) markedly reduced. A year later, hemangioma has not recurred; he is now independent in his daily activities. Early intervention in the subacute stage allows for the complete removal of brainstem cavernomas (BSCs), with minimal risk of complications or sequelae. Proper timing and surgical approach for BSCs can prevent re-bleeding and improve HT after an initial hemorrhage, without any lasting negative consequences.

Reconsideration of Surgical Indication for Prolactin-producing Pituitary Tumor Focusing on Visual Impairment.

Prolactin-producing pituitary tumor (PRLoma) is the most prevalent functional pituitary tumor. If the tumor becomes large, vision can be impaired. In contrast to other pituitary tumors, cabergoline (CAB) is extremely effective for PRLoma and has become the first-line treatment. In this study, we examined our experience with the pharmacological and surgical management of PRLomas with visual impairment (VI) to determine whether VI could be a surgical indication. Further, we discussed the function of surgery in situations where the gold standard of PRLoma treatment was CAB administration. Of the 159 patients with PRLomas (age, 13-77 [mean = 36.3] years; men, 29; women, 130) at Tokyo Women's Medical University Hospital from 2009 to 2021, 18 (age, 15-67 [mean = 35.8] years; men, 12; woman, 6) had VI (subjectively, 12; objectively, 6). They started CAB treatment immediately (maximum dose: 0.5 to 6 mg/week; average: 2.17 mg/week). VI improved in 16 patients (88.9%) but did not improve in 2 (11.1%) requiring surgeries. One of the two patients had a parenchymal tumor resistant to CAB, and the other had a cystic tumor due to intratumoral bleeding. Consequently, CAB is the first-line treatment for PRLomas with VI because of its significantly high rate of improvement. However, close and rigorous surveillance is necessary for cases resistant to CAB, and the correct decision is required regarding surgical interventions at proper timing and appropriate surgical approaches considering the purpose of surgery.

Endoscope-assisted Trans-lamina Terminalis Resection of Chordoid Glioma at the Third Ventricle: A Case Report.

As per the 2021 World Health Organization (WHO) Classification of Tumors of the Central Nervous System, chordoid glioma (CG) is defined as a slow-growing glial neoplasm categorized as grade II tumor. This tumor is primarily located in the anterior part of the third ventricle, often adheres to important surrounding structures, and is hemorrhagic in nature. Therefore, dissecting this tumor is extremely difficult. In this study, we present the case of a 44-year-old man who initially complained of mild headache and was diagnosed with a homogeneous gadolinium-enhanced lesion in the third ventricle via magnetic resonance imaging. The pathological diagnosis based on his biopsy at the previous hospital was CG. The patient demonstrated no neurological deficit at that time, but the tumor had gradually grown, hydrocephalus appeared 2 years after the tumor was detected, and the patient developed short memory disorder and daytime sleepiness. We resected the tumor via the anterior interhemispheric trans-lamina terminalis approach using a microscope and an endoscope. The residual tumor at the blind spot of the microscopic view was resected under an angled rigid endoscopic view using dedicated tools for transsphenoidal surgery. The tumor was grossly resected, and the histopathological diagnosis was CG. Postoperative neurological findings included slight memory disorder and hypothalamic adrenal dysfunction. No tumor recurrence was reported 3 years post resection. The endoscope-assisted anterior interhemispheric trans-lamina terminalis approach was determined useful for CG resection with minimal surgical complications and without tumor recurrence.

Systemic Metastasis of Pediatric Diffuse High-grade Astrocytoma: A Case Report.

Extracranial brain tumor metastases are extremely rare. The etiology, pathophysiology, and clinical progression of systemic metastatic brain cancer remain to be elucidated. We encountered a case of pediatric diffuse high-grade astrocytoma in a four-year-old girl with subcutaneous and lymph node metastases. Numerous metastatic lesions emerged, progressed rapidly, and were difficult to manage despite temozolomide (TMZ) administration. The patient underwent repeated surgical resection for these lesions. Conversely, the primary intracranial lesions responded well to TMZ for some time. However, the patient died 15 months after the initial diagnosis. Extracranial metastasis and highly varying effects of chemotherapy were the characteristic clinical features in this case. Our analysis did not reveal definitive histopathological and molecular factors contributing to this presentation. The lack of notable molecular pathological features illustrates the unpredictability of glioma metastasis, and the treatment for extracranial metastasis remains unknown. A gene panel analysis revealed several genetic aberrations, including PDGFRA, PIK3CA, and NBN mutations. As it is impossible to resect all frequently and rapidly progressing lesions, we stress that the prognosis of metastatic brain tumors is undoubtedly poor if these tumors are refractory to existing treatments, including chemotherapy.

Corrigendum: Photodynamic therapy for malignant brain tumors in children and young adolescents.

[This corrects the article DOI: 10.3389/fonc.2022.957267.].

Clinical Features of Pituitary or Parasellar Tumor Onset with Cranial Nerve Palsy: Surgical Intervention Considerations.

OBJECTIVE: This study aimed to clarify the symptoms of pituitary or parasellar tumor onset with cranial nerve palsy (CNP) and to improve our knowledge of this rare symptom and its most appropriate treatment. METHODS: Among 1281 patients with pituitary or parasellar tumors surgically treated from 2003 to 2020, 30 cases (2.34%; 15 men and 15 women; mean age: 55.6 years, range: 6-83 years) first presenting with CNP were reviewed to evaluate the neurological symptoms, histological diagnosis, interval from onset to surgery, and time before complete CNP recovery. RESULTS: Pathological diagnoses comprised 17 pituitary adenomas, including 10 pituitary apoplexies and 4 adrenocorticotropic hormone-positive adenomas, and 13 other tumors, including 3 chordomas, 2 xanthogranulomas, 2 malignant lymphomas, 2 metastatic tumors, 1 Rathke cleft cyst, 1 plasmacytoma, 1 craniopharyngioma, and 1 neuroendocrine carcinoma. The mechanisms causing CNP were pituitary apoplexy (n = 10), cranial nerve compression or involvement (n = 17), and inflammatory changes (n = 9). As the first manifestation, 20 (66.7%) patients presented with oculomotor nerve palsy, 2 (6.7%) with trochlear nerve palsy, and 13 (43.3%) with abducens nerve palsy. Full recovery of CNP was obtained in 25 patients (83.3%) after surgery alone and in 2 patients (6.7%) after adjuvant therapy. Early surgery provided no significant difference in full recovery rates although it reduced the time to reach full recovery. CONCLUSIONS: It is critical to determine the mechanisms of CNP and intervene surgically to improve symptoms, shorten the duration of the disorder, prevent relapses, and obtain the correct pathological diagnosis to select the proper adjuvant therapy.

Photodynamic therapy for malignant brain tumors in children and young adolescents.

Photodynamic therapy (PDT) targets tumor cell remnants after resection. Here, we evaluated the feasibility of PDT for malignant brain tumors in children and young adolescents. This was a single-center, non-randomized, phase I/II clinical study. The primary endpoints were the safety of treatment with talaporfin sodium (TS) (phase I) and overall survival (OS) after PDT (phase II). The secondary endpoint was progression-free survival (PFS) after PDT. The TS dose was determined by dose escalation from 10 to 20 to 40 mg/m2 for every three cases starting from the initial enrolled case. Eight patients with a mean age of 170.2 months (129-214 months) at the time of PDT received nine procedures with a mean follow-up duration of 16.8 months (1-42 months) after PDT. Histopathological diagnoses included supratentorial anaplastic ependymoma (n = 2), anaplastic astrocytoma (n = 1), diffuse midline glioma with H3K27M mutation (n = 1), glioblastoma (n = 3), and pediatric high-grade glioma (n = 1). The outcome was survival in five patients and death in three patients. Recurrence occurred in six of the eight patients; the remaining two were recurrence-free after PDT. Therefore, OS and PFS were calculated as 21 and 6 months, respectively. Seizures and fevers, which were likely surgery-related symptoms, were commonly observed. Photosensitive skin rashes or liver dysfunction, which are common adverse effects in adults, were not observed. Our results showed that TS can be used safely in children at doses comparable to those used in adults, as there was no major complication associated with TS administration. However, we cannot make a definitive conclusion about the efficacy of PDT because of the small number of participants. Accumulating cases was difficult because of the rarity of pediatric brain tumors and the difficulty in making a preoperative differential diagnosis, considering the wide range of histopathological findings. Moreover, the psychological stress associated with light-shielding management in pediatric patients was more severe than initially expected. In conclusion, TS at doses comparable to those used in adults may be safe for use in children and young adolescents between the ages of 6 and 20 years. However, further studies are needed to clarify its efficacy.

Clinical features and difficulty in diagnosis of Langerhans cell histiocytosis in the hypothalamic-pituitary region.

Langerhans cell histiocytosis (LCH) is a multi-organ disorder that rarely involves the hypothalamic-pituitary region (HPR). HPR-LCH presents with severe progressive pituitary dysfunction and its prognosis is poor. The definitive diagnosis of LCH is considerably difficult and complicated owing to the occurrence of several diseases with similar manifestations in the HPR and its location in the deepest portion of the anterior skull base, in close proximity to important normal structures, severely limiting the size of the biopsy specimen. Chemotherapy is the established treatment modality for LCH; hence, timely and accurate diagnosis of LCH is essential for early therapeutic intervention. We retrospectively reviewed clinical features and biopsy procedures in four patients with HPR-LCH (all female, 28-44 years old) from 2009 to 2020. Maximum diameter of supra-sellar lesions was 23-35 mm and 2 cases had skip lesions. All patients demonstrated central diabetes insipidus, hyper-prolactinemia, and severe anterior pituitary dysfunction. Two of the patients had progressive disease. Furthermore, four patients presented body weight gain, two visual disturbance, and two impaired consciousness. The duration from onset to diagnosis of LCH was 3 to 10 (average 7.25) years. In total, eight operations were performed until final diagnosis. The percentage of correct diagnosis by biopsy was 50% (4/8). Clinical features of HPR-LCH are very similar to those of other HPR diseases, and their symptoms are progressive and irreversible. Clinicians should consider repeated biopsy with a more aggressive approach if the lesion is refractory to steroid therapy, in order to ensure accurate diagnosis and appropriate treatment.

Compact polytetrafluoroethylene assembly-type capillary electrophoresis with chemiluminescence detection.

We have developed a compact polytetrafluoroethylene (PTFE) assembly-type capillary electrophoresis with chemiluminescence (CL) detection system. Luminol-microperoxidase-hydrogen peroxide chemiluminescence reaction was adopted. The device is rectangular in shape (60 mm x 40 mm x 30 mm) and includes three reservoirs (sample, migration buffer, and detection reservoirs) with electrodes. The detection reservoir includes an optical fiber to transport light at the capillary tip to a photomultiplier tube. Isoluminol isothiocyanate (ILITC) was analyzed as a model using this device with fused-silica or polytetrafluoroethylene capillary tubes 10 cm in length. We also used the sample reservoir as a reactor for an immune reaction between anti-human serum albumin immobilized on glass beads and isoluminol isothiocyanate-labeled human serum albumin. The present polytetrafluoroethylene assembly with the capillary tube was useful as a palm-sized analysis device for separation and detection, as well as a reactor.

Non-genomic action of 17beta-estradiol on opening of Ca(2+)- and voltage-activated K+ channel in lacrimal acinar cells.

The effect of the sex hormone 17 beta-estradiol on the opening of Ca(2+)- and voltage-activated K+ channels (BK channels) in the basolateral plasma membrane of mouse lacrimal acinar cells was studied by patch-clamp single-channel recording and Ca(2+)-measurement using fura-2 AM. In intact cells (the cell-attached configuration) using a pipette containing a Na+ -rich solution, estradiol was added to the bath solution, which does not have direct contact with the electrically isolated areas of membrane patch from which the single-channel currents were recorded. Estradiol increased the frequency of opening of the BK channels within a few minutes after its application. The effect of estradiol on the opening of the BK channels in acinar cells in male mice was greater than that in females. In Ca(2+)-measurement using fura-2 AM, estradiol did not increase the level of intracellular Ca2+ during a 5-minute observation period. The application of estradiol with propranolol, a beta-adrenergic receptor blocker, did not increase BK channel opening. The application of estradiol with Rp-cAMPS, an inhibitor of cyclic AMP-dependent protein kinase (protein kinase A), also inhibited the increase in channel opening. The addition of a catalytic unit of protein kinase A to the inside of the excised membrane patch increased the frequency of opening of the BK channels. These results suggest that estradiol interacts with beta-adrenergic receptor on the basolateral membrane and regulates the opening of BK channels by protein phosphorylation via a cyclic AMP pathway, without a change in the Ca2+ level.