Functional characterization of variants found in Japanese patients with hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant form of vascular dysplasia. Genetic diagnosis is made by identifying loss-of-function variants in genes, such as ENG and ACVRL1. However, the causal mechanisms of various variants of unknown significance remains unclear. In this study, we analyzed 12 Japanese patients from 11 families who were clinically diagnosed with HHT. Sequencing analysis identified 11 distinct variants in ACVRL1 and ENG. Three of the 11 were truncating variants, leading to a definitive diagnosis, whereas the remaining eight were splice-site and missense variants that required functional analyses. In silico splicing analyses demonstrated that three variants, c.526-3C > G and c.598C > G in ACVRL1, and c.690-1G > A in ENG, caused aberrant splicing, as confirmed by a minigene assay. The five remaining missense variants were p.Arg67Gln, p.Ile256Asn, p.Leu285Pro, and p.Pro424Leu in ACVRL and p.Pro165His in ENG. Nanoluciferase-based bioluminescence analyses demonstrated that these ACVRL1 variants impaired cell membrane trafficking, resulting in the loss of bone morphogenetic protein 9 (BMP9) signal transduction. In contrast, the ENG mutation impaired BMP9 signaling despite normal cell membrane expression. The updated functional analysis methods performed in this study will facilitate effective genetic testing and appropriate medical care for patients with HHT.

Helmet therapy efficacy and its prediction in Japanese infants with positional plagio- and brachycephaly.

PURPOSE: To provide additional information on optimal start times and therapeutic effectiveness based on treatment outcome of Japanese infants with positional plagio- and brachycephaly (PPB) receiving cranial molding helmet therapy (CMHT). METHODS: In this retrospective cohort study, data from a 3D head scanning system was analyzed from 2173 Japanese infants who completed CMHT. Anterior and posterior symmetry ratio (ASR and PSR) and longitudinal to transverse diagonal ratios (LD/TDR) were calculated based on skull shape at helmet design and at completion of therapy. The outcomes were evaluated using the regression analysis and a predictive model using cranial parameters was developed. RESULTS: The earlier the start of therapy, the greater the therapeutic effect on ASR, PSR, and LD/TDR (ASR, -0.134 percent points (ppt)/day; PSR, -0.086 ppt/day; and LD/TDR, -0.131 ppt/day). In the predictive model, in addition to starting age of the therapy, sex (male), the degree of deformity of the head (DoD) (moderate and severe), quadrant volume, PSR, and head circumference at the start of treatment also had a positive effect on changes in ASR, DoD (moderate and severe), ASR, LD/TDR and transverse diameter for PSR, sex (male), DoD (moderate), quadrant volume, PSR, and head circumference for LD/TDR. CONCLUSION: The starting age of therapy had a relatively smaller contribution to outcome effects. Applying the cranial parameter obtained at the start of treatment to the predictive model helps to predict the effect of CMHT and whether PPB can be treated with CMHT in infants of older age.

Pediatric craniopharyngioma with significantly increased intraoperative visual evoked potential amplitude and postoperative visual acuity improvement: a case report.

Visual evoked potential (VEP) is an established modality that allows safe brain tumor resection and preservation of optical function. We herein present a case of a pediatric craniopharyngioma with significant improvement in the VEP amplitude detected during endoscopic transsphenoidal surgery (ETS) and obvious postoperative improvement in visual acuity. A 13-year-old boy presented with visual acuity disturbance in his right eye and was followed up for 5 months by an ophthalmologist. His visual acuity rapidly worsened, and a suprasellar lesion with calcification was found on brain computed tomography. The patient underwent tumor resection during ETS with intraoperative transcranial VEP monitoring. Gross total tumor resection was achieved without injury to the perforators, including the superior hypophyseal arteries. The VEP amplitude was unstable, and significant waves were not detectable before tumor resection; however, a positive wave was detected after removing most of the tumor and exposing the bilateral optic nerves and optic chiasm. Subsequently, negative and positive VEP waves were continuously detected. Visual acuity improved remarkably on postoperative day 10. This case demonstrated both a significant increase in the intraoperative VEP amplitude and rapid postoperative improvement in visual acuity. We surmised that the preoperative rapid worsening of visual dysfunction, intraoperative increase in the VEP amplitude, and significant postoperative improvement in visual acuity were associated with the compression of the optic nerves by the internal carotid artery, anterior cerebral artery, and tumor.

A case of a pineal parenchymal tumor of intermediate differentiation with bifocal lesions differentiated by negative placental alkaline phosphatase in the spinal fluid.

Placental alkaline phosphatase (PLAP) in the spinal fluid is helpful for the diagnosis of intracranial germinomas. Bifocal lesions involving the pineal and pituitary regions have also been reported as characteristic findings of intracranial germinomas. We present a rare case of a 15-year-old boy with a pineal parenchymal tumor of intermediate differentiation (PPTID) with bifocal lesions negative for PLAP. Magnetic resonance imaging of the brain revealed bifocal mass lesions in the pineal and suprasellar regions and non-communicating hydrocephalus. We initially suspected a germinoma based on imaging findings, but all tumor markers, including PLAP, in the spinal fluid were negative. Based on these results, germinoma was considered less likely, and an endoscopic third ventriculostomy and endoscopic tumor biopsy were performed for diagnosis. The histopathological diagnosis was PPTID, corresponding to World Health Organization grade 3, in both pineal and suprasellar specimens. A craniotomy for tumor removal was performed, resulting in total resection. PLAP is known to have high sensitivity and extremely high negative predictive value for germinomas. Although bifocal lesions highly suggest germ cell tumors, there are exceptions, as in the present case. This case suggests that PLAP measurements are useful for differentiation, leading to appropriate treatment strategies.

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.

Comparison of efficacy between clazosentan and fasudil hydrochloride-based management of vasospasm after subarachnoid hemorrhage focusing on older and WFNS grade V patients: a single-center experience in Japan.

Subarachnoid hemorrhage often leads to poor outcomes owing to vasospasm, even after successful aneurysm treatment. Clazosentan, an endothelin receptor inhibitor, has been proven to be an effective treatment for vasospasms in a Japanese randomized controlled trial. However, its efficacy in older patients (≥ 75 years old) and those with World Federation of Neurosurgical Societies (WFNS) grade V has not been demonstrated. We retrospectively evaluated the efficacy of clazosentan in older patients and those with WFNS grade V, using real-world data. Patients with subarachnoid hemorrhage treated before and after the introduction of clazosentan were retrospectively evaluated. The patients were categorized into two groups (clazosentan era versus pre-clazosentan era), in which vasospasm management and outcomes were compared. Vasospasms were managed with fasudil hydrochloride-based (pre-clazosentan era) or clazosentan-based treatment (clazosentan era). Seventy-eight patients were included in this study: the clazosentan era (n = 32) and pre-clazosentan era (n = 46). Overall, clazosentan significantly reduced clinical vasospasms (clazosentan era: 31.3% versus pre-clazosentan era: 60.9%, p = 0.01), delayed cerebral ischemia (DCI) (9.4% versus 39.1%, p = 0.004), and vasospasm-related morbidity and mortality (M/M) (3.1% versus 19.6%, p = 0.03). In subgroup analysis of older patients or those with WFNS grade V, no significant difference was observed in clinical outcomes, although both DCI and vasospasm-related M/M were lower in the clazosentan era. Clazosentan was more effective than fasudil-based management in preventing DCI and reducing vasospasm-related M/M. Clazosentan could be used safely in older patients and those with WFNS grade V, although clinical outcomes in these patients were comparable to those of conventional treatment.

Loss-of-function mutations in SGCE found in Japanese patients with myoclonus-dystonia.

SGCE myoclonus-dystonia is a monogenic form of dystonia with an autosomal dominant mode of inheritance that co-occurs with a myoclonic jerk. In this study, we present 12 Japanese patients from nine families with this disease. Targeted next-generation sequencing covering major causative genes for monogenic dystonias identified nine distinct SGCE mutations from each of the families: three nonsense, two frameshift, two missense, one in-frame 15 bp deletion, and one splice donor site mutations, of which four were previously unreported. One missense mutation (c.662G>T, p.Gly221Val) was located at the 3' end of exon 5 (NM_001099400), which was predicted to cause aberrant splicing according to in silico predictions. Minigene assays performed together with the c.825+1G>C mutation demonstrated complete skipping of exon 5 and 6, respectively, in their transcripts. The other missense (c.1345A>G, p.Met449Val) and 15 bp deletion (c.168_182del, p.Phe58_Leu62del) mutations showed a significant reduction in cell membrane expression via HiBiT bioluminescence assay. Therefore, we concluded that all the detected mutations were disease-causing. Unlike the other detected mutations, p.Met449Val affects only isoform 3 (NP_001092870 encoded by NM_001099400) among the variously known isoforms of SGCE. This isoform is brain-specific and is mostly expressed in the cerebellum, which supports recent studies showing that cerebellar dysfunction is a key element in the pathophysiology of SGCE myoclonus-dystonia.

Encoding of social exploration by neural ensembles in the insular cortex.

The insular cortex (IC) participates in diverse complex brain functions, including social function, yet their cellular bases remain to be fully understood. Using microendoscopic calcium imaging of the agranular insular cortex (AI) in mice interacting with freely moving and restrained social targets, we identified 2 subsets of AI neurons-a larger fraction of "Social-ON" cells and a smaller fraction of "Social-OFF" cells-that change their activity in opposite directions during social exploration. Social-ON cells included those that represented social investigation independent of location and consisted of multiple subsets, each of which was preferentially active during exploration under a particular behavioral state or with a particular target of physical contact. These results uncover a previously unknown function of AI neurons that may act to monitor the ongoing status of social exploration while an animal interacts with unfamiliar conspecifics.

Tumor volume and calcifications as indicators for preoperative differentiation of grade II/III diffuse gliomas.

PURPOSE: To retrospectively evaluate preoperative clinical factors for their ability to preoperatively differentiate malignancy grades in patients with incipient supratentorial grade II/III diffuse gliomas. METHODS: This retrospective study included 206 adult patients with incipient supratentorial grade II/III diffuse gliomas according to the 2016 World Health Organization classification of tumors of the central nervous system. The cohort included 136 men and 70 women, with a median age of 41 years. Preoperative factors included age, sex, presence of calcifications on computed tomography scans, and preoperative tumor volume measured using preoperative magnetic resonance imaging. RESULTS: In patients with oligodendrogliomas (IDH-mutant and 1p/19q-codeleted), calcifications were significantly more frequent (p = 0.0034) and tumor volume was significantly larger (p < 0.001) in patients with grade III tumors than in those with grade II tumors. Moreover, in patients with IDH-mutant astrocytomas, preoperative tumor volume was significantly larger (p = 0.0042) in patients with grade III tumors than in those with grade II tumors. In contrast, none of the evaluated preoperative clinical factors were significantly different between the patients with grade II and III IDH-wildtype astrocytomas. CONCLUSION: In adult patients with suspicison incipient supratentorial grade II/III diffuse gliomas, presence of calcifications and larger preoperative tumor volume might be used as preoperative indices to differentiate between malignancy grades II and III in oligodendrogliomas (IDH-mutant and 1p/19q-codeleted) and larger preoperative tumor volume might have similar utility in IDH-mutant astrocytomas.

Postsurgical dural supply to the spinal cord arteriovenous malformation in spinal arteriovenous metameric syndrome.

Dural supply from the external carotid system in cerebral arteriovenous malformations (AVMs) is well known, but actual angiographic evidence of dural supply to spinal cord AVMs (SCAVMs) has not been reported. Here, we report a case of dural supply to the conus SCAVM in the spinal arteriovenous metameric syndrome segment 25-30. Thirteen years after spinal surgery (T12-L2 laminoplasty), spinal angiography showed multiple dural supplies from the dorsal somatic branches, prelaminar arteries, and radiculomeningeal arteries to the SCAVM at the level of the previous spinal surgery. To the best of our knowledge, this is the first reported case with dural supply to the spinal cord. This case demonstrates that the extradural and extraspinal branches can supply the spinal cord in rare instances of spinal dural adhesions following repeated hemorrhages and surgical intervention under a metameric link background.

Bilateral Radiofrequency Ventral Intermediate Thalamotomy for Essential Tremor.

INTRODUCTION: With the advent of MR-guided focused ultrasound, the importance of the efficacy and safety of bilateral ventral intermediate (Vim) thalamotomy for essential tremor (ET) has increased. However, reports on bilateral Vim thalamotomy for ET remain scarce. METHODS: To review the results and complications of bilateral Vim thalamotomy for the treatment of ET in the upper extremities, we retrospectively analyzed the patients with ET who underwent bilateral Vim thalamotomy with radiofrequency (RF) thermal coagulation. As bilateral simultaneous thalamotomy can cause surgical complications, thalamotomy was performed in stages. The interval between the first and second thalamotomies was 21.3 ± 14.7 months. We evaluated the efficacy using the Clinical Rating Scale for Tremor (CRST) before and after the first and second treatments, respectively. We also evaluated the complications before and after the first and second treatments, respectively. Moreover, we assessed the adverse events. RESULTS: Seventeen patients were included in the study. The mean follow-up period following the second thalamotomy was 29.3 ± 15.0 months. The CRST part A + B scores were 34.9 ± 9.7, 20.8 ± 7.0, and 7.4 ± 6.8 before, following the first (40.4% improvement, p < 0.0001) and second thalamotomies (78.6% improvement, p < 0.0001), respectively. Nine patients presented with prolonged adverse events, including dysarthria, dysgeusia, dysphagia, tongue numbness, unsteady gait, and postural instability at the last available evaluation. All adverse events were mild and did not interfere with the patient's daily activities. DISCUSSION/CONCLUSIONS: Bilateral Vim thalamotomy with RF thermal coagulation was an effective treatment for ET in both upper extremities. Despite most possible complications being mild, additional studies with a larger sample size are required to ensure patient safety.

Selective surgical mamillo-thalamic tract disconnection in hypothalamic hamartoma results in complete disappearance of gelastic seizures.

Hypothalamic hamartoma is a less common condition characterized by the several types of epileptic seizures including the gelastic type. It is reported that gelastic seizures are resistant to medical treatment with anticonvulsants, while stereotactic thermocoagulation or Gamma Knife radiosurgery are effective for seizure control. Here, we report an individual case where direct surgical resection disconnecting hypothalamic hamartoma from mammillothalamic tract resulted in complete disappearance of gelastic seizures without deterioration of cognitive function. A 6-year-old boy developed gelastic seizures at the age of 2 and suffered from precocious puberty. Anticonvulsants including carbamazepine and zonisamide failed to control seizures. The patient underwent direct division of the mammillothalmic tract by removal of hypothalamic hamartoma partially via anterior interhemispheric approach. It was observed that gelastic seizures disappeared completely after the surgical treatment without any endocrine and cognitive dysfunction for a follow-up period of 14 years. The mammillothalamic tract which connects anterior nucleus of thalamus and mammillary bodies plays a key role in gelastic seizures related to hypothalamic hamartoma. In this case, we disconnected the hamartoma specifically from the mammillary bodies and not from the rest of hypothalamus. Effectively, it enabled permanent control of seizures. This result shows that fibers connecting other hypothalamic structures and the dorsomedial nucleus of thalamus are not involved in gelastic seizure propagation from the hypothalamic hamartoma. When surgical treatment of hypothalamic hamartomas is performed it has high morbidity associated with hypothalamic disorders. Therefore, disconnection between hypothalamic hamartoma and mammillary bodies presents a possibility of reducing hypothalamic damage. Surgical disconnection between hamartoma and mammillothalamic tract carries minimal hypothalamic injury risk and our results suggest that it has the potential of seizure control for intractable gelastic seizures with less complications.

Efficacy of the pedicle trapezius muscle flap for the multisurgical removal of pediatric posterior fossa anaplastic ependymoma.

OBJECTIVE: Exceedingly refractory, pediatric anaplastic ependymoma in many cases requires multisurgical removal. The high risk of poor wound healing and CSF leakage especially at the posterior fossa make this tumor difficult to treat. CASE: A 9-year-old girl has had 4th ventricular anaplastic ependymoma since the age of 3. She experienced tumor removal 8 times including 4 posterior fossa craniotomies because tumors were disseminated not only to the posterior fossa but also to the cerebral hemispheres. She also underwent a dermal graft using a free flap. She experienced CSF leaks and meningitis frequently because the wound healing was poor. We performed a dermal flap closure using a pedicle trapezius muscle flap with a plastic surgeon when we performed the 5th tumor removal. RESULT: We achieved complete wound closure in spite of broad deficiencies in subcutaneous and epidermal tissues. After that, recurrences of posterior fossa tumors presented within a short term, and tumor removal via an incision of a pedicle trapezius muscle flap was performed without recurrence of CSF leaks and meningitis. DISCUSSION AND CONCLUSION: For the first time, we are able to report on the efficacy of using the pedicle trapezius muscle flap for multisurgical removal of pediatric posterior fossa anaplastic ependymoma. The muscle flap was found to be effective because of the multiple surgeries expected, and the pedicle trapezius muscle flap was found to be resilient to multiple surgical procedures. Although advantageous, the dorsal scapular artery which is required for flap creation is actually difficult to harvest. Compared to a flee flap, the pedicle trapezius muscle flap maintains vascular supply. Furthermore, this technique has the possibility of being applied to defective dura mater closure that cannot be watertight due to multiple surgeries. However, it is very important to inform the patient's family not only about the improved efficacy of surgery, but also to raise awareness on consequential cosmetic issues.

Increase in serum vimentin levels in patients with glioma and its correlation with prognosis of patients with glioblastoma.

Early diagnosis of glioma is of great value to improve prognosis. We focused on serum vimentin levels as a useful biomarker for preoperative diagnosis. The aim of this study was to determine whether serum vimentin levels in patients with glioma are significantly higher than those of healthy adult volunteer and whether the serum vimentin level is associated with overall survival (OS) in patients with glioblastoma (GBM). This study included 52 consecutive patients with newly diagnosed glioma and a control group of 13 healthy adult volunteers. We measured serum vimentin levels in blood samples obtained from patients with glioma preoperatively and a control group. Furthermore, we investigated the correlation between serum vimentin levels and OS in patients with GBM. The serum vimentin levels of patients with glioma were significantly higher than those of the control group. The serum vimentin level of 2.9 ng/ml was the optimal value for differentiating patients with glioma from the control group with a sensitivity of 92.3% and specificity of 88.5%. The serum vimentin levels correlated significantly with immunoreactivity for survivin. In 27 patients with GBM, serum vimentin levels (cutoff value, median value 53.3 ng/ml) correlated with OS in univariate and multivariate analyses. Our study revealed that serum vimentin levels of patients with glioma are significantly higher than those of the control group. Therefore, we believe that serum vimentin level might be a useful and practical biomarker for preoperative diagnosis of glioma. Furthermore, high serum vimentin levels correlated significantly with shorter OS in patients with GBM.

Relationship between characteristics of glioma treatment and surgical site infections.

PURPOSE: Surgical site infections (SSIs) after neurosurgery are common in daily practice. Although numerous reports have described SSIs in neurosurgery, reports specific to gliomas are limited. This study aimed to investigate the relationship between SSIs and glioma treatment characteristics, such as reoperations, radiation therapy, and chemotherapy. METHODS: We examined 1012 consecutive patients who underwent craniotomy for glioma between November 2013 and March 2022. SSIs were defined as infections requiring reoperation during the observation period, regardless of their location. We retrospectively analyzed SSIs and patient factors. RESULTS: During the observation period, SSIs occurred in 3.1% (31/1012). In the univariate analysis, three or more surgeries (P = 0.007) and radiation therapy (P = 0.03) were associated with SSIs, whereas intraoperative magnetic resonance imaging (MRI) was not significantly associated (P = 0.35). Three or more surgeries and radiation therapy were significantly correlated with each other (P < .0001); therefore, they were analyzed separately in the multivariate analysis. Three or more surgeries were an independent factor triggering SSIs (P = 0.02); in contrast, radiation therapy was not an independent factor for SSIs (P = 0.07). Several SSIs localized in the skin occurred more than 1 year after surgery. CONCLUSIONS: Undergoing three or more surgeries for glioma is an independent risk factor for SSIs. Glioma SSIs can occur long after surgery. These results are considered characteristic of gliomas. We recommend careful long-term observation of patients at a high risk of SSIs.

Localization and symptoms associated with removal of negative motor area during awake surgery.

BACKGROUND: In awake surgery, cortical mapping may identify the negative motor area (NMA). However, since speech arrest occurs regardless of whether the NMA or the frontal language area (FLA) is stimulated, the presence of speech arrest alone does not distinguish the NMA from the FLA. Furthermore, the exact location and function of the NMA is not well understood. The purpose of this study was to more accurately locate the NMA in a group of cases in which the NMA and FLA could be identified in different brain gyri, and to describe symptoms in cases in which the NMA was removed. METHODS: There were 18 cases of awake surgery at our institution between 2000 and 2013 in which cortical stimulation allowed identification of FLA and NMA in separate brain gyri. In these cases, the pre- and post-removal mapping results were projected onto a 3D model postoperatively. We investigated the symptoms and social rehabilitation in a case in which the tumour invaded the same brain gyrus as the NMA and the NMA had to be resected in combination with the tumour. RESULTS: In cases where the NMA and FLA could be identified in different brain gyri, NMA was localized inferior to the precentral gyrus in all cases. In four cases where NMA was removed with the tumour, apraxia of speech was observed during the surgery; the same symptoms persisted after it, but it improved within a few months, and the patients were able to return to work. CONCLUSION: In cases where NMA and FLA could be identified separately by awake mapping, the NMA was commonly localized inferior to the precentral gyrus. When NMAs were resected in combination with tumour invasion, they did not lead to serious, long-term complications.

Transsinusal embolization of transverse sigmoid sinus dural arteriovenous fistula in a hybrid operating room: A technical note.

BACKGROUND: Using the transverse sinus as a conduit to treat a transverse sigmoid sinus dural arteriovenous fistula is uncommon. This report describes a minimally invasive direct puncture technique for the transverse sinus to treat a complex dural arteriovenous fistula in a hybrid operating room. CASE: The patient was a 64-year-old man with intractable status epilepticus. Digital subtraction angiography demonstrated a right transverse sigmoid sinus dural arteriovenous fistula (Borden type II, Cognard type IIa+b). We performed a transcranial direct puncture because the femoral vein approach was not feasible due to bilateral thrombosed sinuses. Under general anesthesia and park-bench patient positioning, the transverse sinus was exposed and catheterized, and the affected sinus was embolized using microcoils. The fistula was completely obliterated, resolving the status epilepticus. CONCLUSIONS: Direct puncture of the transverse sinus can be effective for treating a transverse sigmoid sinus dural arteriovenous fistula. In a hybrid operating room, combined treatments can be performed comfortably and safely in a single session of general anesthesia. This treatment option is a viable alternative when other methods are unsuccessful.

[Intraoperative Visual Evoked Potential].

In neurosurgery, the intraoperative visual evoked potential(VEP)has recently been used for the management of anterior skull base and parasellar tumors related to the optic pathways to prevent postoperative visual complications. We used light emitting diode photo-stimulation thin pad and stimulator(Unique Medical, Japan). We also recorded the electroretinogram(ERG)simultaneously to exclude technical errors. VEP is defined as an amplitude between the maximum positive wave at 100 ms(P100)and the prior negative wave(N75). In intraoperative VEP monitoring, reproducibility of VEP should be ascertained, particularly in patients with preoperative advanced visual impairment and an intraoperative diminished amplitude. Furthermore, a 50% reduction in the amplitude is critical. In such cases, we should consider suspending or changing surgical manipulation. We have not clearly verified the relationship between the absolute intraoperative VEP value and postoperative visual function. Mild peripheral visual field defects cannot be detected in the present intraoperative VEP system. However, intraoperative VEP with ERG monitoring can serve as a real-time warning to guide surgeons to avoid postoperative visual impairment. We should comprehend the principles, characteristics, disadvantages, and limitations of intraoperative VEP monitoring for reliable and effective utilization.

Prediction of Cross-Clamp-Induced Cerebral Ischemia During Carotid Endarterectomy Using Arterial Blood Flow Assessment.

BACKGROUND: Cross-clamping during carotid endarterectomy (CEA) is associated with the risk of cerebral ischemia. Various studies have evaluated different criteria for detecting cerebral ischemia, but difficulties arise when ischemic changes appear after the carotid artery is cross-clamped and incised. Here, we explored a parameter that can predict cerebral ischemia prior to cross-clamping during CEA using a blood-flow meter. METHODS: The carotid arterial blood flow was measured directly (direct ABF) in the common carotid artery prior to cross-clamping. The anatomical information in preoperative magnetic resonance imaging, cerebral blood flow in xenon-enhanced computed tomography, and carotid peak systolic flow velocity by carotid echo from the skin surface were also evaluated. A decrease in the short-latency somatosensory evoked potentials (SSEP) during cross-clamping to insert a shunt was assessed, and a decrease in amplitude of ≥ 50% was considered an indicator for cerebral ischemia. Surgery was performed under general anesthesia, and a shunt was inserted in all cases. RESULTS: Of 156 CEA patients between April 2013 and March 2020, 30 had decreased SSEP during cross-clamping. The baseline characteristics and intra- and postoperative findings were not significantly different between patients with and without a decrease in SSEP. Among the evaluated parameters, only the direct-ABF ratio (ABF-internal carotid artery/ABF-common carotid artery) differed significantly between the 2 groups (P = 0.011). The direct-ABF ratio ≤ 0.58 was predictive of cerebral ischemia during CEA. CONCLUSIONS: Direct-ABF measurement with an ultrasonic blood-flow meter can be useful for predicting cerebral ischemia prior to carotid artery cross-clamping during CEA.

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.