A New Sarcoma Shortly after Treatment for High-Grade Glioma with Adjuvant Chemoradiation: A Case Report.

Introduction: High-grade gliomas are central nervous system tumors conventionally treated with surgery followed by adjuvant chemoradiotherapy. Secondary cancer due to radiation therapy is a rare yet established phenomenon that typically occurs years after radiation therapy. Case Presentation: In this case, we discuss an early presentation of a second cancer adjacent to the radiation field. This case report is of a 52-year-old male who developed a new scalp sarcoma at the site of primary surgery 8 months after radiation therapy. Genetic testing revealed a heterozygous missense variant in the NF1 gene, a variant of uncertain significance. The report highlights that this case does not conform to the expected criteria for postradiation sarcoma in terms of timing. Conclusion: Secondary cancers may arise earlier than expected, even in phenotypically normal patients, as they may have unmanifested variants of relevant mutations. The question of pre-radiotherapy screening for radiosensitivity syndromes and diseases requires further study, as current data are limited and do not provide enough insight into the significance of different genetic variants.

Recombinant tissue plasminogen activator (rTPA) management for first onset acute ischemic stroke with covid -19 and non-covid -19 patients.

OBJECTIVES: Cerebrovascular stroke (CVS) is one of the well-known complications of coronavirus-2019 (Covid-19), but less is known about the outcome and safety of thrombolytic therapy in these patients. In this study we compare the efficacy and safety of Tissue plasminogen activator (rTPA) in acute ischemic stroke (AIS) patients with or without Covid-19 infection. MATERIALS AND METHODS: A comparative prospective study in which all patients who presented with AIS and eligible for rTPA were recruited from the emergency department and classified into 2 groups (AIS with Covid-19 infection and AIS without Covid-19 as controls). Demographic data, symptoms of Covid-19, clinical examination, neuroimaging, and laboratory investigations were obtained in each patient. National Institute of Health Stroke Scale (NIHSS) and the Modified Rankin Scale (mRS) were assessed before, immediately after rTPA, and 3 months later. RESULTS: There were 22 patients in the COVID-19 group and 25 control patients. Those with COVID-19 were more likely to have a history of smoking and Diabetes Mellitus than controls. On admission, motor symptoms were more severe in patients with COVID-19. COVID-19 patients were more likely to have symptomatic intra-cerebral hemorrhage and radiological hemorrhagic transformation than controls. Onset to door time (ODT) and onset to successful reperfusion time were significantly longer in Covid-19 patients than controls. Clinical improvement and frequency of re-occlusion and recurrent ischemic stroke at 3 months follow-up did not differ between groups, although there was higher number of deaths (27.3%) in the Covid-19 group than controls (16%). CONCLUSIONS: Using rTPA is safe and effective in patients with AIS with or without COVID-19 infection despite the high frequency of hemorrhagic transformation and high number of deaths.

A double blind randomized clinical trial of the effectiveness of low frequency rTMS over right DLPFC or OFC for treatment of obsessive-compulsive disorder.

We compared the effectiveness of low frequency repetitive transcranial magnetic stimulation over right dorsolateral prefrontal cortex (DLPFC), right orbitofrontal cortex (OFC) and sham for treatment of obsessive-compulsive disorder (OCD) and sought to determine possible predictors of effective treatment. Sixty OCD patients participated and were randomly allocated to one of the 3 treatment groups. Treatment was administered daily for 10 days. Assessments were made at the beginning and end of therapy as well as three months later using the Yale-Brown obsessive compulsive scale (Y-BOCS), Hamilton Anxiety Rating Scale (HAM-A), Beck Depression Inventory (BDI), and Clinical Global Impression - Severity scale (CGI-S). There were no significant demographic or clinical differences between the groups at baseline. One-way repeated measures ANOVA showed that participants in all 3 groups improved their scores on all rating scales following treatment. A two-way repeated measures ANOVA revealed a significant time and group interaction due to the fact that both active treatment groups outperformed the sham group, although there was no significant difference between the two. Percent improvement had significant negative correlations with the following factors: duration of illness, baseline Y-BOCS, HAM-A, and BDI. We conclude that rTMS over either right DLPFC or OFC has a therapeutic effect on OCD symptoms. Patients with lower Y-BOCS and fewer comorbidities responded best to rTMS.

Ten-year survival in glioblastoma patient with neurofibromatosis type 1: illustrative case.

BACKGROUND: Gliomas are commonly detected in patients with neurofibromatosis type 1 (NF1) at an early age. Few patients with NF1 are diagnosed with glioblastoma. The course of management, response to therapy, and prognosis of such patients are unknown. Few reports have shown longer-than-average survival rates for patients with NF1 with glioblastoma. OBSERVATIONS: A 27-year-old man with NF1 presented with symptoms of high intracranial pressure. Imaging and pathology showed left frontotemporal glioblastoma. Gross total resection was achieved, and concurrent chemoradiotherapy was administered. Recurrence of tumor was detected 48 months later, and the patient underwent tumor debulking and concurrent chemoradiotherapy. The patient received first-, second-, and third-line chemotherapy (temozolomide, bevacizumab, bevacizumab/irinotecan) with good tolerance and has survived >10 years since then with good functional status. LESSONS: This case demonstrates >10 years overall survival of glioblastoma in a patient with NF1. Reports of patients with NF1 with longer survival may be attributed to the young age at diagnosis and relatively better tolerance for therapy. It might also support the growing evidence of a unique subset of glioblastoma associated with NF1 and opens the door for a more molecular targeted therapy in the future.

Alteration of Gut Microbiota in Alzheimer's Disease and Their Relation to the Cognitive Impairment.

BACKGROUND: Dysbiosis of gut microbiota has been reported to be enrolled in the pathogenesis of Alzheimer's disease (AD). However, there is a lack of relevant studies on this topic in Egyptian patients with AD. OBJECTIVE: To investigate different species of gut microbiota in Egyptian patients with AD and correlate microbiota bacterial abundance with clinical data. METHODS: The study included 25 patients with AD and 25 healthy volunteers as age and sex-matched controls. Clinical data was taken for each patient, including medical history and examination; Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were assessed for each participant. Bacterial DNA was extracted from stool, and abundance quantified via qPCR using 16S rRNA group-specific primers. RESULTS: Akkermansia, Enterobacteria, Bacteroidetes, Bacillus cereus, Prevotella, and Clostridium cluster IV were more abundant in the AD group than in the control group, although there was significantly less abundance of Bifidobacterium spp., Firmicutes, and Actinobacteria in patients with AD than in controls, whereas no such significance was found for lactic acid bacteria between both groups. Lactic acid bacteria and Prevotella abundance was negatively correlated with cognitive impairment (p = 0.03 with MMSE, and p = 0.03 with MoCA). Prevotella abundance was positively correlated with age of onset and duration of illness and negatively correlated with smoking and coronary heart disease (p = 0.007, p = 0.03, p = 0.035, and p = 0.047, respectively). CONCLUSION: The current work highlighted a significant relationship between AD and gut microbiota dysbiosis. A higher abundance of Prevotella species and lactic acid bacteria was correlated with cognition.

Breast-cancer detection using blood-based infrared molecular fingerprints.

BACKGROUND: Breast cancer screening is currently predominantly based on mammography, tainted with the occurrence of both false positivity and false negativity, urging for innovative strategies, as effective detection of early-stage breast cancer bears the potential to reduce mortality. Here we report the results of a prospective pilot study on breast cancer detection using blood plasma analyzed by Fourier-transform infrared (FTIR) spectroscopy - a rapid, cost-effective technique with minimal sample volume requirements and potential to aid biomedical diagnostics. FTIR has the capacity to probe health phenotypes via the investigation of the full repertoire of molecular species within a sample at once, within a single measurement in a high-throughput manner. In this study, we take advantage of cross-molecular fingerprinting to probe for breast cancer detection. METHODS: We compare two groups: 26 patients diagnosed with breast cancer to a same-sized group of age-matched healthy, asymptomatic female participants. Training with support-vector machines (SVM), we derive classification models that we test in a repeated 10-fold cross-validation over 10 times. In addition, we investigate spectral information responsible for BC identification using statistical significance testing. RESULTS: Our models to detect breast cancer achieve an average overall performance of 0.79 in terms of area under the curve (AUC) of the receiver operating characteristic (ROC). In addition, we uncover a relationship between the effect size of the measured infrared fingerprints and the tumor progression. CONCLUSION: This pilot study provides the foundation for further extending and evaluating blood-based infrared probing approach as a possible cross-molecular fingerprinting modality to tackle breast cancer detection and thus possibly contribute to the future of cancer screening.

Highlights on the Management of Oligometastatic Disease.

Purpose: The understanding of oligometastatic disease (OMD) is rapidly evolving and with this comes the ability to utilize a number of modalities that excel in the localized control of disease. It has been identified that there are no clear guidelines based on high-level evidence to standardized approaches toward the management of OMD. These highlights have been developed to provide a road map for all health-care professionals who are involved in the management of OMD to support standardized patient care. Methods: The Saudi Lung Cancer Guidelines Committee is a part of the Saudi Lung Cancer Association which, in turn, is part of the Saudi Thoracic Society. Considering that lung cancer constitutes a major proportion of OMD prevalence, the committee took the initiative to develop national highlights to support the management of OMD within Saudi Arabia. The committee members are national clinical leaders who collaborated with international expertise to establish these highlights to serve as a general clinical pathway in the management of OMD. Results: Standardization of the indications to diagnose oligometastases and patient selection criteria including ineligibility criteria for treatment are the basis of the highlights. Treatment approaches including surgical and the variety of radiotherapeutical options are discussed in relation to specific oligometastatic sites. Acceptable measurements for response to treatment and the future for the treatment of OMD conclude the development of the highlights. Conclusion: These are the first national highlights addressing this important disease in oncology. The implementation of these highlights as guidelines requires a robust multidisciplinary team and access to specific technology and expertise. These highlights are based on the most recent findings within the literature but will require repeated review and updating due to this rapidly evolving field in disease management.

Effect of chronic nicotine consumption on motor cortical excitability: A transcranial magnetic stimulation study.

OBJECTIVES: Transcranial magnetic stimulation (TMS) allows exploration of the mode of action of neuroactive substances in the human brain, and allows evaluation of neuronal networks, which might be involved in the action of nicotine. The aim of the present study was to explore motor cortex excitability in chronic smokers and non-smokers using TMS. METHODS: The study included 50 healthy subjects, of whom 25 were chronic smokers and 25 were age- and sex-matched non-smokers. Number of cigarettes per day and duration of smoking in years were documented. Serum level of cotinine was measured. Resting and active motor threshold (RMT, AMT) and input-output curves (I/O) were performed to assess corticospinal excitability. The duration of the contralateral silent period (cSP) at different ranges of stimulation intensities and ipsilateral silent period (iSP) were used as measures of inhibition. RESULTS: There were no significant differences either in RMT or AMT between groups. I/O curve showed a significant intensity×group interaction (P=0.008). This was attributable to significantly higher amplitudes of MEP among smokers than non-smokers especially at 130, 140 and 150% of RMT (P=0.0001 and P=0.03 and 0.02 respectively). The mean duration of the cSP at different intensities and iSP duration were similar in both groups. Nicotine level and smoking index were correlated respectively with rMT and iSP (P=0.03 and 0.01). CONCLUSION: The present results confirm previous findings by Grundey et al. (2013) that chronic nicotine consumption is characterized by hyperexcitability of corticospinal output. We speculate that it is a secondary adaptation to long-term nicotine use with high inter-individual variance.

TMS excitability study in essential tremor: Absence of gabaergic changes assessed by silent period recordings.

BACKGROUND: Essential tremor (ET) is thought to emerge from activity in a distributed cerebello-thalamo-cortical network. It has been proposed that the network goes into oscillation because of abnormal GABAergic inhibitory transmission. OBJECTIVE: To test this idea by investigating GABAergic circuitry in motor cortex using transcranial magnetic stimulation (TMS). METHODS: Motor cortex excitability was examined using TMS in 21 patients with essential tremor and in 20 control subjects. Resting and active motor threshold (RMT, AMT) and input-output curves examined corticospinal excitability. Contralateral silent period (cSP) at a different range of stimulation intensities, and the ipsilateral silent period (iSP) using a stimulus intensity of 150% RMT were used as measures of GABAergic function. RESULTS: RMT and AMT were significantly lower in patients than controls and patients had a steeper I/O curve. However, there were no significant differences in either cSP at different intensities or in iSP. CONCLUSION: We found no evidence in favour of the GABA hypothesis in ET.

Repetitive transcranial magnetic stimulation for treatment of tardive syndromes: double randomized clinical trial.

Tardive syndromes (TDS) typically manifest 3 months or later after exposure to antipsychotic drugs, and unfortunately have no satisfactory medical treatment. We explored the possibility of using therapeutic repetitive transcranial magnetic stimulation (rTMS). Twenty-six patients were allocated to receive real or sham rTMS over the hand/arm area of motor cortex (M1). Each received a daily total of 2000 rTMS pulses (20 Hz at 100% rMT: 1000 stimuli per hemisphere) for 10 consecutive days. Outcome was assessed using the Abnormal Involuntary Movement Scale (AIMS) and TMS measures of M1 excitability. Three patients in the sham group failed to complete the study. At baseline, there was no significant difference between the groups in age, sex distribution, duration of illness, AIMS score and drug treatment. rTMS improved symptoms in both groups. However, there was a greater reduction in the AIMS score of the real rTMS group compared with the sham group (real, 8.3 ± 1.7 points; sham 1.2 ± 3.3; repeated measure analysis ANOVA Time X Group interaction P = 0.001). The same trends were observed in the clinical subscales. Following treatment, MEP amplitudes at higher intensities (140, and 150%) increased more in the real treatment group than in the sham group. This is the first clinical trial study of bilateral hemispheric rTMS in patients with TDS and suggests that 20 Hz rTMS might be a feasible treatment option in patients unresponsive to "first-line" treatment.Clinical trial registration ClinicalTrials.gov Identifier: NCT03145311.

Changes in recruitment of motor cortex excitation and inhibition in patients with drug-induced tardive syndromes.

OBJECTIVES: It has recently been suggested that drug-induced tardive syndromes (TS) might be due to maladaptive plasticity, which increases motor excitability in cerebral cortex and basal ganglia. In order to test this hypothesis, we performed the first measurements of cortical excitability in TS. METHODS: Motor cortex excitability was examined using transcranial magnetic stimulation (TMS) in 22 TS patients and compared with that in 20 age and sex-matched healthy individuals. Resting and active motor threshold (RMT, AMT) and input-output curves (I/O curves) assessed corticospinal excitability. The duration of the contralateral silent period (cSP) at a range of stimulation intensities and ipsilateral silent period (iSP) were used as measures of inhibition. RESULTS: There were no significant differences in RMT and AMT between patients and controls, although the input-output curves were significantly steeper in patients. The cSP (at different stimulus intensities) and iSP were both longer in the patients compared to the control group. However, most of this difference could be accounted for by increased recruitment of motor evoked potentials (MEPs) in patients. CONCLUSION: TS is characterized by hyperexcitability of corticospinal output that might contribute to the lack of selectivity in muscle recruitment and contribute to excess involuntary movement. The findings are opposite to those in naturally-occurring hyperkinesia such as Sydenham's and Huntington's chorea, suggesting a fundamental difference in the pathophysiology.

Saudi lung cancer management guidelines 2017.

BACKGROUND: Lung cancer management is getting more complex due to the rapid advances in all aspects of diagnostic and therapeutic options. Developing guidelines is critical to help practitioners provide standard of care. METHODS: The Saudi Lung Cancer Guidelines Committee (SLCGC) multidisciplinary members from different specialties and from various regions and healthcare sectors of the country reviewed and updated all lung cancer guidelines with appropriate labeling of level of evidence. Supporting documents to help healthcare professionals were developed. RESULTS: Detailed lung cancer management guidelines were finalized with appropriate resources for systemic therapy and short reviews highlighting important issues. Stage based disease management recommendation were included. A summary explanation for complex topics were included in addition to tables of approved systemic therapy. CONCLUSION: A multidisciplinary lung cancer guidelines was developed and will be disseminated across the country.

Spectrum of epilepsy - prevalence, impact, and treatment gap: an epidemiological study from Al-Quseir, Egypt.

BACKGROUND: Epidemiology continues to be an important research tool in the study of epilepsy and related disorders, providing a better understanding of the frequency, causes, and natural history of the disorder. OBJECTIVE: To estimate the prevalence of epilepsy in Al-Quseir, Red Sea Governorate, Egypt, and its magnitude of treatment gap. METHODS: The study was part of a door-to-door study, including every door, to screen all inhabitants in Al-Quseir (33,818 inhabitants) by three specialists of neurology and 15 female social workers (for demographic data collection) using a standardized screening questionnaire. All suspected cases were subjected to detailed history, clinical examination, and electroencephalogram. Neuroimaging studies and estimation of serum drug level were done in select cases if needed. RESULTS: The study revealed that the lifetime prevalence rate of epilepsy in Al-Quseir is 5.5/1,000, with the highest peak during early childhood, while that of active epilepsy is 3.3/1,000 population. The annual incidence rate is 48/100,000, and the age-specific incidence rate has a U-shaped pattern with two peaks of incidence in early infancy and elderly life. Localization-related epilepsy is the most frequently encountered type (58.8%). The treatment gap of epilepsy in Al-Quseir is 83.8%. CONCLUSION: The lifetime prevalence of epilepsy in Al-Quseir city, Red Sea Governorate, was 5.5/1000.

Prevalence of neurological disorders in Al Quseir, Egypt: methodological aspects.

Methodology and strategy play a very important role in epidemiological studies. Determination of the study area, geographical features, facilities, difficulties, and key personnel from the same area are important factors for successful methodology. Over 31 months (July 1, 2009 to January 31, 2012), a screening and an examination survey were carried out to ascertain the prevalence of epilepsy, stroke, dementia, cerebellar ataxia, migraine, cerebral palsy, Parkinsonism, chorea, athetosis, dystonia, trigeminal neuralgia, Bell's palsy, multiple sclerosis, spinal cord disorders, and attention deficit hyperactivity disorders in Al Quseir, Red Sea Governorate, Egypt. A total of 33,285 people were screened by three neurologists in a door-to-door manner, including every door, using a standardized Arabic questionnaire to detect any subject with a neurological disorder. The methodological aspects of this project were carried out through eight phases: (1) data collection; (2) preparation; (3) screening; (4) case ascertainment; (5) investigations; (6) classifications; (7) data entry; and (8) statistics and tabulations. The results of this study reveal that the total prevalence of neurological disorders in Al Quseir was 4.6% and higher among females (5.2%) than males (3.9%). The highest prevalence was recorded in the elderly population (60+ years [8.0%]) and among the age group 18-39 years (5.4%).