CD68 in Cerebral Aneurysms of Smokers and Nonsmokers: An Immunohistochemical Analysis.

BACKGROUND: There is some evidence indicating that inflammation of the aneurysmal wall is related to aneurysmal growth and rupture. The presence of CD68 may indicate greater inflammatory activity. The objective of this study is to evaluate CD68 immunoexpression in surgically resected brain aneurysms and its association with smoking. METHODS: The resected brain aneurysmal walls after microsurgical clipping were envoyed to immunohistochemistry investigation. The objective was to evaluate the expression of CD68 and CD34 antibodies. The associations between inflammatory markers, smoking, and rupture were tested using Fischer's exact test. RESULTS: CD68 immunoexpression in the tunica media was associated with larger aneurysms: 7.0 mm (7.0-9.0 mm) versus 5.0 mm (3.5-5 mm; p = 0.011). There was no statistically significant association between smoking and CD68 expression in the tunica media (p = 0.234) or in either the tunica media or the tunica intima (p = 0.628). There was also no statistically significant association between hemorrhagic presentation of the aneurysm and CD68 expression in the tunica media (p = 0.689) or in either the tunica media or the tunica intima (p = 0.348). Therefore, the presence of CD68-positive cells in the aneurysmal walls indicates an association with size, especially if the tunica media is exclusively compromised (p = 0.011). CONCLUSION: Immunohistochemistry investigation for CD68 antibodies was used to determine histiocytic infiltration. Adequately powered studies are necessary to further investigate the association between CD68-positive cells and both smoking history and hemorrhagic presentation of aneurysms.

B-Cell Lymphoma Intramedullary Tumor: Case Report and Systematic Review.

Intramedullary tumors represent the major cause of spinal cord injuries, and its symptoms include pain and weakness. Progressive weakness may concomitantly occur in the upper and lower limbs, along with lack of balance, spine tenderness, sensory loss, trophic changes of extremity, hyperreflexia, and clonus. The study protocol was in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A systematic search of the MEDLINE electronic database was performed to identify the studies reporting the clinical features of children and adults who presented with an intramedullary lymphoma. Twenty-one studies were included, reporting 25 cases. Manuscripts were excluded if the full-text article was not available, original data were not reported (e.g., review articles), or if the main disease was not intramedullary lymphoma. A structured data extraction form was employed to standardize the identification and retrieval of data from manuscripts. To enlighten the discussion, a case is also presented. An 82-year-old woman with Fitzpatrick skin type II, diagnosed and treated for non-Hodgkin's lymphoma 7 years ago, was admitted with mental confusion and memory loss for the past 2 months-evolving with recurring falls from her own height. One day before admission, she displayed Brown-Séquard syndrome. An expansive lesion from C2 to C4 in the cervical spinal cord was found and a hypersignal spinal cord adjacent was described at the bulb medullary transition to the C6-C7 level. A primary spinal cord tumor was considered, as well as a melanoma metastasis, due to the lesion's flame pattern. The patient presented a partial recovery of symptoms and a reduction of the spinal cord edema after being empirically treated with corticosteroids, but the lesion maintained its extent. Subsequently, a large diffuse B-cell lymphoma with nongerminal center was found in open body biopsy, infiltrating neural tissue. The main objective of the present study is to report a surgical case treated for a large diffuse B-cell lymphoma, in addition to presenting the results of a systematic review of primary intramedullary spinal cord lymphoma.

Dyke-Davidoff-Masson Syndrome: Main clinical and radiological findings- systematic literature review.

INTRODUCTION: Dyke-Davidoff-Masson syndrome (DDMS), or cerebral hemiatrophy, was first described in 1933. It is characterised by cerebral injury that causes hypoplasia in one of the cerebral hemispheres. The disease has different clinical degrees and two aetiologies: congenital and acquired. Radiological findings depend on the degree of injury and the patient's age at the time. OBJECTIVE: To provide information on the main clinical and radiological characteristics of this disease. METHODS: A systematic review of the PubMed, MEDLINE, and LILACS databases was conducted using only one keyword. Dyke-Davidoff-Masson syndrome. A total of 223 studies were identified, and the results are presented in tables and graphics. RESULTS: The mean age of the patients was 19.44 (0-83 years), and the majority were male (55.32%). The most common types of epileptic seizures were generalised tonic-clonic seizures (31 cases), focal impaired awareness seizures (20 cases), focal motor seizures (13 cases), focal to bilateral tonic-clonic seizures (nine cases), and focal myoclonic seizures (one case). The main features of the disease were rapid deep tendon reflexes and extensor cutaneous-plantar tendon reflexes (30 cases - 16%), contralateral hemiparesis or hemiplegia (132 cases - 70%), gait alterations (16 cases - 9%), facial paralysis (nine cases - 5%), facial asymmetry (58 cases - 31%), limb asymmetry (20 cases - 11%), delayed developmental milestones (39 cases - 21%), intellectual disability (87 cases - 46%), and language/speech disorders (29 cases - 15%). Left hemisphere atrophy was the most prevalent. CONCLUSION: DDMS is a rare syndrome, and several questions regarding this disease remain unanswered. This systematic review aims to elucidate the most common clinical and radiological aspects of the disease and emphasises the need for further investigation.

Is percutaneous balloon compression better than microvascular decompression to treat trigeminal neuralgia? A systematic review and meta-analysis.

BACKGROUND: Trigeminal neuralgia (TN) is a neuropathic pain that affects one or more branches of the trigeminal nerve. Surgical options after pharmacological failure are Microvascular Decompression (MVD) or percutaneous procedures, which include Balloon Compression (PBC). This study aims to describe pain outcomes and complications after PBC and MVD procedures for patients with trigeminal neuralgia. METHODS: We performed a systematic review and meta-analysis on PubMed, EMBASE, LILACS, and Web of Science databases up to April 2022, following PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and meta-Analysis). Articles that separately describe pain outcome for MVD and PBC were included. MINORS tool was used for bias assessment. Meta-analysis results are presented in forest plot and funnel plot. RESULTS: 853 studies were assessed for screening, and 11 studies met the inclusion criteria for this review. A total of 1046 patients underwent PBC and 1324 underwent MVD. The subgroup analysis for patients without multiple sclerosis shows that MVD was associated with lower number of patients with pain than PBC, with an OR value of 0.54 (95 % CI 0.34-0.84). All other analyses evidenced a tendency for better outcomes after the MVD procedure, but with no statistically significant difference. CONCLUSION: Considering short and long pain relief, recurrence of pain and total complications for MVD and PBC, our study found that MVD is the best surgical option available for trigeminal neuralgia.

Preoperative scale proposal based on clinical outcome for elderly patients with ruptured intracranial aneurysms undergoing microsurgery.

INTRODUCTION: Life expectancy in individuals has increased in recent years. There is no consensus in the literature on the best treatment for a ruptured aneurysm in the elderly (> 60 years), but some places only have microsurgery as a therapeutic strategy. This work aims to develop a prognostic scale for ruptured intracranial aneurysms in the elderly. MATERIAL AND METHODS: Two thousand five hundred thirty patients with subarachnoid hemorrhage were retrospectively evaluated in the last ten years, and 550 of them were elderly. We developed a prognostic scale from the analysis of medical records, clinical and tomographic features that had statistical significance. Glasgow Coma Outcome (GOS) was the outcome of interest and p value < 0,05 was considered statistically significant. RESULTS: Five hundred fifty patients were evaluated, and the comorbidities that were independent variables for poor prognosis were smoking and arterial hypertension; clinical variables were Hunt-Hess, modified Rankin and Glasgow Coma Scale; tomographic was Fisher scale. Poor outcome was defined as GOS ≤ 3. Poor surgical outcomes were more remarkable in the high-risk factor categories, being 6.41 times higher among individuals who had 3 to 4 risk factors and 8.80 times higher among individuals with 5 to 6 risk factors. CONCLUSION: In some vascular neurosurgery services worldwide, microsurgery is the only therapeutic option. This scale aimed at the elderly patient individualizes the treatment and can predict the clinical outcome in ruptured intracranial aneurysms.

Primary central nervous system lymphoma in a patient with multiple sclerosis using fingolimod.

Primary central nervous system lymphoma (PCNSL) is an uncommon lymphoproliferative disease associated with immunosuppression. Here, we report the case of a patient with multiple sclerosis, under treatment with fingolimod (FTY720, Gilenya) for 4 years, who developed this condition. Although the causal relationship cannot be established, there are cases in the literature that describe the appearance of lymphoma after the use of this medication. Considering the high mortality of PCNSL, epidemiological studies are necessary to establish a relationship between its arising and the use of immunosuppressants.

What is the ideal grade of resection for parasagittal meningiomas with the invasion of superior sagittal sinus? Simpson I or Simpson II resection? A retrospective observational study.

Background: Parasagittal meningioma (PSM) is a tumor located in the parasagittal angle which extends to and/ or invades the superior sagittal sinus (SSS). Surgical resection of the PSM, the standard treatment in such cases, poses a challenge for neurosurgery, particularly where there is an invasion of the SSS. This is due to the risk of complications through injury to the adjacent vascular structures. The objective of the study was to perform a comparative evaluation of the surgical techniques for total resection of the PSM (Simpson Grade [SG] I and SG II), which present the highest rates of success in terms of the following variables: mortality, recurrence, and postoperative complications. Methods: Fifty-six patients undergoing resection surgery for PSM with the invasion of the SSS were enrolled. The patients were divided into two groups: Group A, comprising 26 cases of patients subjected to SG I PSM resection surgery and Group B, with 31 cases of patients subjected to SG II PSM resection surgery, with preservation of the SSS. Results: The results showed that Group B had lower rates of postoperative deficit (P = 0.026), zero mortality, and reduced recurrence. The use of complementary radiotherapy for atypical meningiomas (WHO II) in Group B was satisfactory in controlling the disease. Conclusion: The Simpson II, with preservation of the SSS, was better as it diminishes the vascular risks of surgery, reduces the frequency of severe postoperative deficit, and reduces mortality.

Miller-Fisher syndrome after first dose of Oxford/AstraZeneca coronavirus disease 2019 vaccine: a case report.

INTRODUCTION: Miller-Fisher Syndrome (MFS) is a variant of Guillain-Barré syndrome (GBS), an acute immune-mediated neuropathy, which manifests as a rapidly evolving areflex motor paralysis. This syndrome presents as a classic triad: ophthalmoplegia, areflexia, and ataxia. MFS is usually benign and self-limited. CASE REPORT: A Caucasian patient was admitted to our hospital with the flu, loss of bilateral strength in the lower limbs and upper limbs and sudden-onset ataxia 7 days after receiving a first dose of the Oxford/AstraZeneca COVID-19 vaccine. On neurological examination, the patient had Glasgow Coma Scale score of 15, with absence of meningeal signs; negative Babinski sign; grade 2 strength in the lower limbs and grade 4 strength in the upper limbs; axial and appendicular cerebellar ataxia; and peripheral facial diparesis predominantly on the right, without conjugate gaze deviation. Cerebrospinal fluid (CSF) was collected on admission, and analysis revealed albuminocytological dissociation with CSF protein of 148.9 mg/dL; leukocytes, 1; chlorine, 122; glucose, 65 mg/mL; red cells, 2; and non-reactive venereal disease research laboratory test result. The COVID-19 IgG/IgM rapid immunological test was negative. Electroneuromyography revealed a recent moderate-grade and primarily sensory and motor demyelinating polyneuropathy with associated proximal motor block. DISCUSSION AND CONCLUSION: Miller-Fisher Syndrome may be related to events other than infections prior to neuropathy, as in the case reported here. The patient presented strong correlations with findings for MFS reported in the literature, such as the clinical condition, the results of electroneuromyography, and results of the CSF analysis typical for MFS. When treatment was provided as proposed in the literature, the disease evolved with improvement. Ultimately, the diagnosis of incomplete MFS was made, including acute ataxic neuropathy (without ophthalmoplegia).

[Surgical approaches to petroclival meningiomas Part 2: narrative review of what we learned with 30 cases]. / Abordajes quirúrgicos de los meningiomas petroclivales Parte 2: revisión narrativa y lo que aprendimos con 30 casos.

Background: The surgical ressection of petroclival meningiomas is challenging due to its deep location and relationship with vital neurovascular structures. Usually they are benign injuries, but they can involve or infiltrate skull base bones, dura mater and brainstem. This makes the total removing very difficult or impossible without causing neurological deficits. The objective of this study is to review the surgical approaches used on the treatment of petroclival meningiomas and the knowledge which we achieved upon the surgical management of 30 cases. Methods: Series of 30 petroclival meningioma-cases. In the beginning of our series we used petrous approach for all the cases, however, with the acquiring of experience, we are indicating the retrosigmoid approach, leaving the petrous and skull-orbito-zigomatics approaches for selected cases. Results: Owing to the difficulty of the access, the petroclival meningiomas usually require different surgical approaches and have distint surgical difficulties. There are three main approaches: fronto-orbito-zigomatics and variants; petrous and variants and retrosigmoid, and they can be combined. The choice for a surgical approach is usually on the location and size of the tumor, on the skull shape, the involvement of venous structures and according to the surgeon´s experience. Conclusion: Petroclival meningiomas are rare and complex on the skull base. The adequate choice is crucial to achieve the good surgical result.

[Surgical Approaches to Petroclival Meningiomas Part 1: Microsurgical Anatomy]. / Abordajes quirúrgicos de meningiomas petroclivales parte 1: anatomía microquirúrgica.

Background: Most petroclival meningiomas are benign tumors, but their neurosurgical treatment is one of the greatest challenges in this field. Acquiring a deep practical knowledge of brain anatomy is the first step on the path to successfully meeting this challenge. To this end, the present paper is divided into two parts. The first regards the microsurgical anatomy and surgical approaches used in the management of petroclival meningiomas. The second correlates the brain anatomies of the 30 cases of petroclival meningiomas which the senior author (GRI) has operated on. Methods: Eight cadaver heads were dissected using surgical microscopes at the University of Arkansas microsurgery laboratory. The heads were stabilized in a Mayfield device to simulate surgical conditions and colored silicon was injected to highlight the differences between arteries and veins. The approaches performed were: cranio-orbital zygomatic, posterior and anterior petrosectomy, and retrosigmoid. Results: Three main surgical approaches were chosen to treat petroclival meningiomas: the pterional approach and its variants, the petrous approach and its variants, and the retrosigmoid approach. To rationalize the choice of approach, the clivus was separated into superior, middle, and inferior thirds. Conclusion: Several surgical approaches are useful in accessing the petroclival region. Acquiring a practical knowledge of this anatomy in a microsurgical laboratory is fundamental for any surgeon who intends to operate on petroclival meningiomas.

Success of lateral cervical spinal cord stimulation for the treatment of chronic neuropathic refractory pain.

BACKGROUND: Spinal cord stimulation (SCS) is traditionally performed by implanting surgical leads along the midline of the spinal cord, over the dorsal columns. Here, we present a patient who successfully underwent lateral cervical SCS to treat chronic refractory neuropathic pain. METHODS: A 46-year-old female, with a schwannoma involving the right axillary nerve, presented with a chronic refractory right upper extremity pain syndrome. The tumor was located between the fibers of the teres minor and the posterior deltoid, and measured 2.2 cm in diameter. After 8 months of analgesics, opioids, physiotherapy, and acupuncture, the patient underwent surgery; however, the tumor was unresectable (i.e., due to significant adjacent vascular/neural structures). Three months later, she had a midline C6-C7 laminectomy for placement of a right-sided epidural SCS lead (i.e., containing 16 electrode contacts). RESULTS: Within 4 days following this SCS procedure, the patient's pain completely resolved; at 10 postoperative months, she still remains pain free. CONCLUSION: Lateral SCS at the C6-C7 level provided a safe and effective option for the relief of chronic neuropathic pain attributed to an unresectable schwannoma of the right axillary nerve in a 46-year-old female.

Single-Nucleotide Variants in microRNAs Sequences or in their Target Genes Might Influence the Risk of Epilepsy: A Review.

Single-nucleotide variant (SNV) is a single base mutation at a specific location in the genome and may play an import role in epilepsy pathophysiology. The aim of this study was to review case-control studies that have investigated the relationship between SNVs within microRNAs (miRs) sequences or in their target genes and epilepsy susceptibility from January 1, 2010 to October 31, 2020. Nine case-control studies were included in the present review. The mainly observed SNVs associated with drug-resistant epilepsy (DRE) risk were SNVs n.60G > C (rs2910164) and n.-411A > G (rs57095329), both located at miR-146a mature sequence and promoter region, respectively. In addition, the CC haplotype (rs987195-rs969885) and the AA genotype at rs4817027 in the MIR155HG/miR-155 tagSNV were also genetic susceptibility markers for early-onset epilepsy. MiR-146a has been observed as upregulated in human astrocytes in epileptogenesis and it regulates inflammatory process through NF-κB signaling by targeting tumor necrosis factor-associated factor 6 (TRAF6) gene. The SNVs rs2910164 and rs57095329 may modify the expression level of mature miR-146a and the risk for epilepsy and SNVs located at rs987195-rs969885 haplotype and at rs4817027 in the MIR155HG/miR-155 tagSNV could interfere in the miR-155 expression modulating inflammatory pathway genes involved in the development of early-onset epilepsy. In addition, SNVs rs662702, rs3208684, and rs35163679 at 3'untranslated region impairs the ability of miR-328, let-7b, and miR-200c binding affinity with paired box protein PAX-6 (PAX6), BCL2 like 1 (BCL2L1), and DNA methyltransferase 3 alpha (DNMT3A) target genes. The SNV rs57095329 might be correlated with DRE when a larger number of patients are evaluated. Thus, we concluded that the main drawback of most of studies is the small number of individuals enrolled, which lacks sample power.

Rare complication of ventriculoperitoneal shunt: Ectopic distal catheter in a Grynfeltt hernia - case report.

BACKGROUND: Ventriculoperitoneal shunts (VPSs) insertion is the most common used intervention in cases of hydrocephalus. The main postoperative complications are infections and catheter obstructions. Although the literature has well-documented cases describing migration of the distal catheter, this rare presentation can become more confusing when occurring in conjunction with some unusual preexistent morbidity in the patient, as a Grynfeltt hernia. CASE DESCRIPTION: This study reports a rare case of a VPS postoperative migration, in which the distal catheter exits the abdominal cavity through a Grynfeltt hernia. This condition was not discovered until the catheter fistulated through the overlying skin. The Grynfeltt hernia is the most uncommon among the lumbar ones and it's asymptomatic in the majority of the cases, being hardly diagnosed. CONCLUSION: The unusualness of the reported case deserves furthermore discussion to properly evaluate these underlying mechanisms of catheter migration.

Dorsal Root Entry Zone Lesioning: Systematic Review

Introduction Dorsal root entry zone (DREZ) leasioning (DREZ-otomy) is considered an effective treatment for chronic pain due to spinal cord injuries, brachial and lumbosacral plexus injuries, postherpetic neuralgia, spasticity, and other conditions. The objective of the technique is to cause a selective destruction of the afferent pain fibers located in the dorsal region of the spinal cord. Objective To identify and review the effectiveness and the main aspects related to DREZ-otomy, as well as the etiologies that can be treated with it. Methods The PubMed, MEDLINE and LILACS databases were used as bases for this systematic review, having the impact factor as the selection criteria. The 23 selected publications, totalizing 1,099 patients, were organized in a table for systematic analysis. Results Satisfactory pain control was observed in 70.1% of the cases, with the best results being found in patients with brachial/lumbosacral plexus injury (70.8%) and the worst, in patients with trigeminal pain (40% to 67%). Discussion Most of the published articles observed excellent results in the control of chronic pain, especially in cases of plexus injuries. Complications are rare, and can be minimized with the use of new technologies for intraoperative monitoring and imaging. Conclusion DREZ-otomy can be considered a great alternative for the treatment of chronic pain, especially in patients who do not tolerate the side effects of the medications used in the clinical management or have refractory pain.

Skin erosion in deep brain stimulation procedures: Using the temporalis muscle to treat this complication - A technical note.

BACKGROUND: Skin erosion is a common complication after deep brain stimulator procedures. Despite being a relatively common event, there is no standard surgical technique or a widely accepted guideline for managing this kind of complication. METHODS: We describe a case of cutaneous erosion in the connector's site of deep brain stimulation case, surgically managed with anterior displacement of the connectors and overlapping and wrapping the connections within the temporal muscle. RESULTS: Postoperatively, the patient did well and achieved complete resolution of the skin erosion, with no signs of infection or new skin lesions. CONCLUSION: This technique demonstrated to be effective in this case in the long-term follow-up.

Spinal intramedullary abscess due to Candida albicans in an immunocompetent patient: A rare case report.

BACKGROUND: A spinal intramedullary abscess is a rare clinical entity in which patients classically present with a subacute myelopathy and progressive paraplegia, sensory deficits, and/or bowel and bladder dysfunction. We report the second case of spinal intramedullary abscess caused by Candida albicans to ever be published and the first case of its kind to be surgically managed. CASE DESCRIPTION: A 44-year-old female presented with severe lumbar pain associated with paraparesis, incontinence, and paraplegia. She reported multiple hospital admissions and had a history of seizures, having already undergone treatment for neurotuberculosis and fungal infection of the central nervous system unsuccessfully. Nevertheless, no laboratory evidence of immunosuppression was identified on further investigation. Magnetic resonance imaging showed a D10-D11, well-circumscribed, intramedullary mass within the conus, which was hypointense on T1-weighted imaging and hyperintense on T2/STIR weighted. The patient underwent surgery for removal and biopsy of the lesion, which provided the diagnosis of an intramedullary abscess caused by C. albicans, a very rare condition with only one case reported in literature so far. CONCLUSION: C. albicans intramedullary abscess is a very rare clinical entity, especially in immunocompetent patients. We highlight C. albicans as an important etiology that must be considered in differential diagnosis. Critical evaluation of every case, early diagnosis, timely referral and surgical management of the abscess is essential to improve neurological outcome.

Rosai-Dorfman disease mimicking images of meningiomas: Two case reports and literature review.

BACKGROUND: Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytic proliferative disorder classically as a massive cervical lymphadenopathy. However, over the years, extranodal locations were confirmed with the central nervous system involvement in less than 5% of cases, which is marked as a significant differential diagnosis of meningiomas, with which they are widely confused due to the similarity of their radiological images. CASE DESCRIPTION: We report a 37-year-old man and 45-year-old man who were diagnosed with intracranial RDD but whose radiological images mimic meningiomas, requiring anatomopathological and tumor's immunohistochemistry for definitive diagnosis. Moreover, a review of 184 publications with 285 cases of intracranial involvement of this disease was also performed, comparing these findings with those brought in the previous studies. CONCLUSION: Intracranial Rosai-Dorfman tumors should always be remembered as differential diagnosis of meningiomas since they are similar radiologically and macroscopically. Once remembered and diagnosed, the lesion must be treated following the same pattern of resection done in meningiomas and, treatment's differences will not occur in the surgical excision technique, but in complementary chemotherapy implementation, radiotherapy, and even with radiosurgery aid, depending on the case. Thus, it is possible to obtain better results than with just the isolated surgical procedure.

An unusual case of lead migration in occipital nerve stimulation: A case report and literature review.

BACKGROUND: Lead migration is a complication associated with occipital nerve stimulation (ONS). We present a rare case in which fibrosis in the stress relief loop caused lead migration in the treatment of occipital neuralgia. CASE DESCRIPTION: A 30-year-old woman with a 5-year history of refractory occipital neuralgia, who had been under ONS therapy for 2 months, presented with a sudden onset of typical occipital neuralgia pain associated with cervical muscles spasms and myoclonus. A skull radiography showed lead migration. The patient underwent surgery for lead repositioning. During surgery, we identified extensive fibrosis throughout the stress relief loop that produced several constriction points. The fibrosis in the stress relief loop increased tension on the lead during head-and-neck movement, causing progressive migration of the lead. CONCLUSION: Although lead migration is a common complication of ONS, its association with fibrosis in the stress relief loop has not, to the best of our knowledge, been reported before. Lead migration can directly affect treatment outcome and it is, therefore, important to fully understand the possible mechanisms that can cause it and how to promptly manage them.

Cervical Cordotomy in Terminal Cancer: Pain Relieving in Oncological Treatment

Cordotomy consists in the discontinuation of the lateral spinothalamic tract (LST) in the anterolateral quadrant of the spinal cord, which aims to reduce the transference of nociceptive information in the dorsal horn of the gray matter of the spinal cord to the somatosensory cortex. The main indication is for patients with terminal cancer that have a low life expectancy. It improves the quality of life by relieving pain. The results are promising and the pain relief rate varies between 69 and 100%. Generally speaking, the complications are mostly temporary and not remarkable.