Craniocervical junction involvement in inflammatory arthritis: a single-center radiologic study.

Background/aim: Craniocervical junction (CCJ) can be involved in inflammatory arthritis. We aimed to define types of CCJ involvement in rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA) and compare them with patients without inflammatory arthritides. Materials and methods: In this retrospective analysis, cervical CT or MRIs of patients with RA, SpA, or PsA, taken for any reason between 2010 and 2020, according to ICD-10 codes, were scanned. Demographic data of the patients were recorded. CCJ involvements (atlantoaxial, vertical, or subaxial subluxation, odontoid process involvement) were reevaluated by an experienced radiologist. The control group consisted of consecutive patients without inflammatory arthritis. Results: Exactly 459 patients (204 RA, 200 SpA, and 55 PsA) and 78 patients in the control group were included in the study. CCJ involvement was detected in 101 (49.5%) RA, 53 (26.5%) SpA, 10 (18.2%) PsA, and 4 patients (5.1%) in the control group (p < 0.001). The odontoid process was one of the main targets, especially in RA patients (69 (33.8%)), which was significantly higher than in the SpA, PsA, and control groups. Although vertical subluxation (VS) was numerically higher in the RA and SpA groups compared to the control group, VS-related brainstem compression was relatively uncommon: 6 (2.9%) in RA, 1 (0.5%) in AS, and none in the PsA and control groups. Conclusion: CCJ involvement can often be detected in patients with inflammatory arthritis, especially in RA and SpA patients. The odontoid process is the main target of inflammation.

Does Combined Fractionated Stereotactic Radiotherapy and Immunotherapy Change the Outcome of Recurrent High-Grade Gliomas?

Background Radiotherapy (RT) with immune checkpoint inhibitors (ICI) has yielded good responses in many cancers. We aimed to report the results of combined fractionated stereotactic radiotherapy (FSRT) and ICI in patients with recurrent high-grade glioma. Methodology Patients were treated with FSRT and nivolumab which were continued until progression or toxicity. The Response Assessment in Neuro-oncology and Immunotherapy Response Assessment in Neuro-oncology criteria were used to assess treatment response on magnetic resonance imaging. Treatment-related toxicity was noted in all patients. Results A total of eight patients were included. Recurrence was detected after a median of 5.8 months following the first RT, all in the treatment field. FSRT (3 × 8 Gy) was applied with neoadjuvant, concurrent, and adjuvant nivolumab. After a median follow-up of 21.3 months from diagnosis and 12.6 months from recurrence, one patient was alive and seven succumbed to the disease. The median overall survival was 20.9 months after diagnosis and 12.9 months after recurrence. The median progression-free interval was 2.3 months after FSRT. The local control (LC) rate was 62.5% with a median local recurrence-free survival of nine months. Progression in other regions of the brain was observed in four patients with a median progression-free survival of 2.1 months. Acute toxicity was not observed. ICI-related grade 3 late pneumonitis was observed in two patients, and grade 1 late thyroid toxicity in two patients. One patient with pneumonitis also developed osteoporosis and radiation necrosis. Conclusions A high LC rate was achieved with concurrent FSRT and ICI with a severe late toxicity rate of 25%. This combination can be an option in recurrent high-grade gliomas.

International consensus classification of hippocampal sclerosis and etiologic diversity in children with temporal lobectomy.

INTRODUCTION: The distribution of hippocampal sclerosis (HS) subtypes, according to the classification of the International League Against Epilepsy (ILAE), has been reported mainly in adult patients. We aimed to review the pathological findings in children who had anterior temporal lobectomy accompanied with amygdalohippocampectomy, in view of the current classification, and evaluate postsurgical outcome with respect to HS subtypes in childhood. METHODS: Seventy children who underwent temporal resections for treatment of medically refractory epilepsy, with a minimum follow-up of 2 years, were included; the surgical hippocampus specimens were re-evaluated under the HS ILAE classification. RESULTS: Neuropathological evaluations revealed HS type 1 in 38 patients (54.3%), HS type 2 in 2 (2.8%), HS type 3 in 21 patients (30%), and no HS in 9 patients (12.9%). Of 70 patients, 23 (32.9%) had dual pathology, and the most common pattern was HS type 3 with low-grade epilepsy-associated brain tumors (LEAT). The distribution of HS types with respect to age revealed that HS type 3 and no HS subgroups had significantly more patients younger than 12 years, compared with those of HS type 1 (90.5%, 77.8% vs 47.4%, respectively). History of febrile seizures was higher in HS type 1. Prolonged/recurrent febrile seizures were most common in patients 12 years and older, whereas LEAT was the most common etiology in patients under 12 years of age (p < 0.001). Patients with HS type 1 had longer duration of epilepsy and an older age at the time of surgery compared with patients with HS type 3 and no HS (p: 0.031, p: 0.007). At final visit, 74.3% of the patients were seizure-free. Seizure outcome showed no significant difference between pathological subtypes. CONCLUSIONS: Our study presents the distribution of HS ILAE subtypes in an exclusively pediatric series along with long-term seizure outcome. The study reveals that the leading pathological HS subgroup in children is HS type 1, similar with adult series. Hippocampal sclerosis type 2 is significantly less in children compared with adults; however, HS type 3 emerges as the second most predominant group because of dual pathology, particularly LEAT. Further studies are required regarding clinicopathological features of isolated HS in pediatric cohort. Seizure-free outcome was favorable and similar in all HS types in children. The proportion of HS types may be better defined in pediatric patients with temporal resections, as the current HS ILAE classification becomes more widely used, and may help reveal the surgical and cognitive outcome with respect to HS types.

Combination of Paclitaxel and R-flurbiprofen loaded PLGA nanoparticles suppresses glioblastoma growth on systemic administration.

Malignant gliomas are highly lethal. Delivering chemotherapeutic drugs to the brain in sufficient concentration is the major limitation in their treatment due to the blood-brain barrier (BBB). Drug delivery systems may overcome this limitation and can improve the transportation through the BBB. Paclitaxel is an antimicrotubule agent with effective anticancer activity but limited BBB permeability. R-Flurbiprofen is a nonsteroidal antienflammatory drug and has potential anticancer activity. Accordingly, we designed an approach combining R-flurbiprofen and paclitaxel and positively-charged chitosan-modified poly-lactide-co-glycolic acid (PLGA) nanoparticles (NPs) and to transport them to glioma tissue. NPs were characterized and, cytotoxicity and cellular uptake studies were carried out in vitro. The in vivo efficacy of the combination and formulations were evaluated using a rat RG2 glioma tumor model. Polyethylene glycol (PEG) modified and chitosan-coated PLGA NPs demonstrated efficient cytotoxic activity and were internalized by the tumor cells in RG2 cell culture. In vivo studies showed that the chitosan-coated and PEGylated NPs loaded with paclitaxel and R-flurbiprofen exhibited significantly higher therapeutic activity against glioma. In conclusion, PLGA NPs can efficiently carry their payloads to glioma tissue and the combined use of anticancer and anti-inflammatory drugs may exert additional anti-tumor activity.

Epilepsy in neurofibromatosis type 1: Diffuse cerebral dysfunction?

INTRODUCTION: Neurofibromatosis type 1 (NF1) is accompanied by epileptic seizures in 4-7% of patients. We examined clinical, electrophysiological, and radiological features associated with epilepsy in our NF1 series in order to identify risk factors. METHODS: We reviewed data of 641 pediatric patients with NF1 diagnosis according to National Institutes of Health (NIH) criteria in Hacettepe University records from January 2008-August 2018. Demographic features, NF1-related clinical and imaging characteristics, age at onset of epilepsy, seizure semiology, and frequency, electroencephalogram (EEG) findings, and response to treatment were noted. RESULTS: Twenty-six patients with NF1, 15 male, 11 female, had epilepsy. Age at seizure onset was 6 months to 13 years. Seizure semiology was focal with impaired awareness (n = 9, 34%), focal aware motor (n = 2, 8%), focal to bilateral tonic-clonic (n = 3, 12%), generalized tonic-clonic (n = 7, 28%), absence (n = 3, 12%), infantile spasms (n = 1), and unclassified type (n = 1). None had a history of status epilepticus. The EEG findings were normal for age in ten patients (38%). Others had focal (n = 8, 30%), generalized (n = 7, 27%), or multifocal (n = 1, 4%) discharges. On brain magnetic resonance imaging (MRI) signal intensity changes typical for NF1 (neurofibromatosis bright objects, NBOs) were the most common finding (80%), followed by normal MRI (20%). There was no relation between the localization of NBOs and discharges on EEG. Seventeen patients (65%) were seizure-free at the time of the study; 11 of them still under medication including four on multiple antiepileptic drugs. The rate of learning problems and NBO were significantly higher in patients with NF1 with epilepsy compared to those without. DISCUSSION: Epilepsy in NF1 is associated with relatively infrequent seizures and good response to treatment. Learning disorders are markedly frequent in this group, irrespective of the severity of epilepsy. The absence of correlation between the localizations of epileptiform discharges and lesions on MRI support the role of cellular or synaptic mechanisms rather than structural causes in the pathogenesis of epilepsy.

Farnesylthiosalicylic acid-loaded lipid-polyethylene glycol-polymer hybrid nanoparticles for treatment of glioblastoma.

OBJECTIVES: We aimed to develop lipid-polyethylene glycol (PEG)-polymer hybrid nanoparticles, which have high affinity to tumour tissue with active ingredient, a new generation antineoplastic drug, farnesylthiosalicylic acid (FTA) for treatment of glioblastoma. METHOD: Farnesylthiosalicylic acid-loaded poly(lactic-co-glycolic acid)-1,2 distearoyl-glycerol-3-phospho-ethanolamine-N [methoxy (PEG)-2000] ammonium salt (PLGA-DSPE-PEG) with or without 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) hybrid nanoparticles has been prepared and evaluated for in-vitro characterization. Cytotoxicity of FTA-loaded nanoparticles along with its efficacy on rat glioma-2 (RG2) cells was also evaluated both in vitro (in comparison with non-malignant cell line, L929) and in vivo. KEY FINDINGS: Scanning electron microscopy studies showed that all formulations prepared had smooth surface and spherical in shape. FTA and FTA-loaded nanoparticles have cytotoxic activity against RG2 glioma cell lines in cell culture studies, which further increases with addition of DOTAP. Magnetic resonance imaging and histopathologic evaluation on RG2 tumour cells in rat glioma model (49 female Wistar rats, 250-300 g) comparing intravenous and intratumoral injections of the drug have been performed and FTA-loaded nanoparticles reduced tumour size significantly in in-vivo studies, with higher efficiency of intratumoral administration than intravenous route. CONCLUSION: Farnesylthiosalicylic acid-loaded PLGA-DSPE-PEG-DOTAP hybrid nanoparticles are proven to be effective against glioblastoma in both in-vitro and in-vivo experiments.

A Rare Pediatric Case of Neurocysticercosis Misdiagnosed As Brain Abscess.

Neurocysticercosis is a parasitic infection of the central nervous system caused by the larval stage of Taenia solium. Although this zoonotic infection is one of the major public health problems in some developing countries, it is extremely rare in Turkey. In this article, we present the case of a pediatric patient with neurocysticercosis who was misdiagnosed with brain abscess because of focal seizures in another hospital.

Mesenchymal stem cell application in children with subacute sclerosing panencephalitis.

Subacute sclerosing panencephalitis (SSPE) is a serious, often fatal disease that responds poorly to current treatment modalities. Recently, the ability of mesenchymal stem cells (MSCs) to produce neurotrophic factors and inflammatory molecules has placed them among potential treatment agents for neurological conditions. We report the results of four patients treated with MSC for SSPE. The patients were followed up clinically, and by periodical laboratory evaluations, magnetic resonance imaging (MRI), and electroencephalography. One patient deteriorated to stage III of the disease, two patients remained in the same stage, and one died from disease progression and respiratory problems. Neurological findings and electroencephalography scores were consistent with the clinical course of the patient whereas MRI showed new inflammatory lesions in two patients. This is the first report of the application of MSC in SSPE. No benefit is demonstrated.

Amyloidoma of the temporal bone and upper cervical spine; presentation of a rare clinical entity with a brief literature review.

The amyloidoses comprise a heterogeneous group of diseases characterized by the extracellular deposition of an insoluble protein complex in various tissues. Amyloidomas in bone are most common in patients with systemic amyloidosis and plasma cell dyscrasias. Decreased clearance of beta2 microglobulin frequently causes excessive amyloid deposition in the musculoskeletal system in patients with a history of chronic renal failure and long-term dialysis treatment. Calvarial and/or upper cervical amyloid depositions are rarely seen in clinical practice; therefore the diagnosis requires high index of suspicion and special staining of the tissue. In this article, we present a patient with amyloidoma at the right temporal bone and upper cervical spine. The etiology, radiological findings and differential diagnosis were briefly discussed in the highlights of relevant literature. Amyloidomas should be particularly kept in mind in patients with a history of long-term dialysis therapy, plasma cell dyscrasias or long-standing inflammatory diseases. Differential diagnosis mostly encounters benign or malign mesenchymal neoplasms of the dura and skull base, metastatic tumors, plasmacytoma and brown tumor in the calvarium, as well as primary osseous tumors or metastatic lesions in the spine.

An unusual central nervous system involvement in rheumatoid arthritis: combination of pachymeningitis and cerebral vasculitis.

Severe primary central nervous system (CNS) involvement such as vasculitis and pachymeningitis can rarely occur in rheumatoid arthritis (RA) even in the absence of systemic disease activation. The authors illustrate a female patient with well-controlled RA who presented with headaches, encephalopathy, seizures and relapsing focal neurological deficits. Primary rheumatoid cerebral vasculitis and pachymeningitis were diagnosed based on suggestive brain magnetic resonance (MR) imaging, MR angiography, cerebrospinal fluid analysis and cerebral angiography. MR showed abnormal leptomeningeal enhancement and hyperintense FLAIR signal in the cortical subarachnoid spaces consistent with pachymeningitis. Cerebral angiography findings were consistent with vasculitis. Aggressive treatment resulted in significant clinicoradiological resolution. Cerebral vasculitis is a rare but certain manifestation of RA. This complication can be diagnosed in the presence of suggestive angiographic and CSF findings. The condition may be steroid resistant, and needs to be treated more aggressively.

Mycoplasma pneumoniae-associated transverse myelitis with unexpected rapid response to macrolide therapy: a case report.

A seven-year-old boy admitted with the complaints of fever, weakness in legs, sensory loss in lower limb, and difficulty in voiding lasting for two weeks. His initial symptoms also included cough and fever. His spinal magnetic resonance imaging scan demonstrated acute transverse myelitis, and Mycoplasma pneumoniae-specific IgM and IgG antibodies were found to be positive in cerebrospinal fluid (CSF) and serum samples. He was treated with a single high-dose intravenous immunoglobulin (2 g/kg/dose) and clarithromycin. Mycoplasma pneumoniae is a frequent cause of upper and lower respiratory tract infections in children. Central nervous system (CNS) manifestations are among the most frequent extrapulmonary complications during the course of the disease. They occur most frequently in children, usually within three weeks after the onset of respiratory illness, with an incidence of approximately 1 in 1,000 patients. In this report, we present a seven-year-old boy with transverse myelitis during the course of Mycoplasma pneumoniae infection with serological confirmation both in serum and CSF samples.

Reversible posterior leukoencephalopathy syndrome: report of three cases.

Reversible posterior leukoencephalopathy syndrome is characterized clinically by headache, abnormalities of mental status and visual perception, and seizures. Despite its diverse causes, common precipitating factors are defined as abrupt elevations of blood pressure, renal decompensation, fluid retention, and immunosuppressive therapy. We report three children with reversible posterior leukoencephalopathy syndrome presenting with generalized seizures and headache. The causes of reversible posterior leukoencephalopathy syndrome were considered to be acute hypertension and immunosuppressive therapy in case 1 with systemic lupus erythematosus, chemotherapy (vincristine and/or actinomycin-D) and hyponatremia in case 2, and acute hypertension in case 3, admitted with a familial Mediterranean fever attack. In light of these cases, we review the literature for the etiology, clinical and laboratory findings, and pathogenetic mechanisms of the disease.

Congenital infiltrating lipomatosis of the face with ipsilateral hemimegalencephaly.

An extremely rare case of congenital infiltrating lipomatosis of the face (CILF) associated with ipsilateral hemimegalencephaly is reported in a 3-month-old boy. MRI not only thoroughly evaluated the extent of the lesion, but also demonstrated the cerebral anomaly. MRI is indispensable in the evaluation of patients suspected of having CILF.