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.

Surveillance Study of Acute Neurological Manifestations among 439 Egyptian Patients with COVID-19 in Assiut and Aswan University Hospitals.

BACKGROUND: COVID-19 can be accompanied by acute neurological complications of both central and peripheral nervous systems (CNS and PNS). In this study, we estimate the frequency of such complications among hospital inpatients with COVID-19 in Assiut and Aswan university hospitals. MATERIALS AND METHODS: We screened all patients with suspected COVID-19 admitted from 1 June to 10 August 2020 to the university hospitals of Assiut and Aswan in Upper Egypt. Clinical and laboratory tests, CT/MRI of the chest and brain, and neurophysiology study were performed for each patient if indicated. RESULTS: 439 patients had confirmed/probable COVID-19; neurological manifestations occurred in 222. Of these, 117 had acute neurological disease and the remainder had nonspecific neuropsychiatric symptoms such as headache, vertigo, and depression. The CNS was affected in 75 patients: 55 had stroke and the others had convulsions (5), encephalitis (6), hypoxic encephalopathy (4), cord myelopathy (2), relapse of multiple sclerosis (2), and meningoencephalitis (1). The PNS was affected in 42 patients: the majority had anosmia and ageusia (31) and the others had Guillain-Barré syndrome (4), peripheral neuropathy (3), myasthenia gravis (MG, 2), or myositis (2). Fever, respiratory symptoms, and headache were the most common general symptoms. Hypertension, diabetes mellitus, and ischemic heart disease were the most common comorbidities in patients with CNS affection. CONCLUSION: In COVID-19, both the CNS and PNS are affected. Stroke was the most common complication for CNS, and anosmia and/or ageusia were common for PNS diseases. However, there were 6 cases of encephalitis, 2 cases of spinal cord myelopathy, 2 cases of MG, and 2 cases of myositis.

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.

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.

Prognostic Value of Tumor Infiltrating Lymphocytes in Locally Advanced HER2 Enriched Breast Cancer.

PURPOSE: We aim to study the association between stromal tumor infiltrating lymphocytes (TILs) level and disease free survival (DFS) in a group of ER and PR negative, HER2+ locally advanced breast cancer patients who underwent curative intent surgery. METHODS: This is a retrospective cohort study including 66 locally advanced hormone receptor-negative; HER2+ breast cancer patients presented between 2013 and 2015 at NCI-Cairo, Egypt. Enrolled patients had at least clinically T3 and/or node positive disease either clinically or radiologically. Metastatic workup included CT and bone scans or PET-CT. Patients with hormone receptor positive, HER2 negative, inadequate paraffin block and who lost follow up before or immediately after curative surgery were excluded. Patients were followed from breast surgery till relapse date for a minimum of 36 months. TILs and CD8 antigen were assessed on paraffin-embedded blocks using immunohistochemistry. RESULTS: Patients with a median age of 52 years presented with clinical T3 stage (53%) and N1 stage (61%). Modified radical mastectomy was performed in 79%. Only 41% received neoadjuvant chemotherapy and 56% received trastuzumab. TILs were 50, 17 and 33% for absent, intermediate and extensive groups and CD8+ lymphocytes were present in 80% of cases. At the end of follow-up period, 23 patients (35%) were found to have disease recurrence either loco-regional (22%) or distant (78%). TILs were 14, 4 and 5% for absent, intermediate and extensive respectively; while CD8+ lymphocytes were absent in 6% and present (≥1%) in 17%. Higher DFS was recorded for patients with extensive TILs level only who received trastuzumab. CONCLUSION: High TILs is good prognosis in HER2 enriched breast cancer provided that patients received HER2 directed therapy. Moreover, CD8+ lymphocytes are highly representative and maybe used as an alternative for TILs. We recommend considering TILs and specifically CD8+ as one of the risk factors that predict prognosis of HER2+ breast cancer.

Acute symptomatic seizures and COVID-19: Hospital-based study.

BACKGROUND AND PURPOSE: Post COVID-19 seizures are relatively rare. The aim of the present study was to estimate the frequency of acute symptomatic seizures among patients with COVID-19 and to discuss possible pathophysiological mechanisms. MATERIAL AND METHODS: Out of 439 cases with COVID-19 that were admitted to Assiut and Aswan University hospitals during the period from 1 June to 10 August 2020, 19 patients (4.3 %) presented with acute symptomatic seizures. Each patient underwent computed tomography (CT) or magnetic resonance imaging (MRI) of the brain and conventional electroencephalography (EEG). Laboratory investigations included: blood gases, complete blood picture, serum D-Dimer, Ferritin, C-reactive protein, renal and liver functions, and coagulation profile. RESULTS: Of the 19 patients, 3 had new onset seizures without underlying pathology (0.68 % out of the total 439 patients); 2 others (0.46 %) had previously diagnosed controlled epilepsy with breakthrough seizures. The majority of cases (14 patients, 3.19 %) had primary pathology that could explain the occurrence of seizures: 5 suffered a post COVID-19 stroke (3 ischemic and 2 hemorrhagic stroke); 6 patients had COVID-related encephalitis; 2 patients were old ischemic stroke patients; 1 patient had a brain tumor and developed seizures post COVID-19. CONCLUSION: acute symptomatic seizure is not a rare complication of post COVID-19 infection. Both new onset seizures and seizures secondary to primary brain insult (post COVID encephalitis or recent stroke) were observed.

Case Report: Guillain-Barré Syndrome Associated With COVID-19.

Guillain-Barré syndrome (GBS) is a potentially fatal, immune-mediated disease of the peripheral nervous system that is usually triggered by infection. Only a small number of cases of GBS associated with COVID-19 infection have been published. We report here five patients with GBS admitted to the Neurology, Psychiatry, and Neurosurgery Hospital, Assiut University/Egypt from July 1 to November 20, 2020. Three of the five patients were positive for SARS-CoV-2 following polymerase chain reaction (PCR) of nasopharyngeal swabs on day of admission and another one had a high level of IgM and IgG; all had bilateral ground-glass opacities with consolidation on CT chest scan (GGO) and lymphopenia. All patients presented with two or more of the following: fever, cough, malaise, vomiting, and diarrhea with variable duration. However, there were some peculiarities in the clinical presentation. First, there were only 3 to 14 days between the onset of COVID-19 symptoms and the first symptoms of GBS, which developed into flaccid areflexic quadriplegia with glove and stocking hypoesthesia. The second peculiarity was that three of the cases had cranial nerve involvement, suggesting that there may be a high incidence of cranial involvement in SARS-CoV-2-associated GBS. Other peculiarities occurred. Case 2 presented with a cerebellar hemorrhage before symptoms of COVID-19 and had a cardiac attack with elevated cardiac enzymes following onset of GBS symptoms. Case 5 was also unusual in that the onset began with bilateral facial palsy, which preceded the sensory and motor manifestations of GBS (descending course). Neurophysiological studies showed evidence of sensorimotor demyelinating polyradiculoneuropathy, suggesting acute inflammatory polyneuropathy (AIDP) in all patients. Three patients received plasmapheresis. All of them had either full recovery or partial recovery. Possible pathophysiological links between GBS and COVID-19 are discussed.

Clinical and Radiological Characteristics of Acute Cerebrovascular Diseases Among Egyptian Patients With COVID-19 in Upper Egypt.

Background and Purpose: There is little information on the acute cerebrovascular complications of coronavirus disease 2019 (COVID-19) in Egypt. The aim of this study was to estimate the proportion of acute cerebrovascular disease (CVD) among COVID-19 patients and evaluate their clinical and radiological characteristics in comparison with non-COVID-19 CVD. Materials and Methods: In a retrospective study, COVID-19 patients whom presented with CVD in Assiut and Aswan University Hospitals were compared with non-COVID-19, CVD patients, admitted to Qena University Hospital, prior to the pandemic. The following data were collected: clinical history and presentation, risk factors, comorbidities, brain imaging (MRI or CT), chest CT, and some laboratory investigations. Results: Fifty-five (12.5%) of the 439 patients with COVID-19 had acute CVD. Of them, 42 (9.6%) had ischemic stroke while 13 patients (2.9%) had hemorrhagic CVD. In the 250 cases of the non-COVID-19 group, 180 had ischemic stroke and 70 had hemorrhagic stroke. A large proportion of patients with COVID-19 who presented with ischemic stroke had large vessel occlusion (LVO), which was significantly higher than in non-COVID-19 patients with CVD (40 vs. 7.2%, P < 0.001). Comorbidities were recorded in 44 (80%) cases. In COVID-19 ischemic stroke patients, risk factors [hypertension and ischemic heart disease (IHD)] and comorbidities (hepatic and renal) were significantly higher than those in non-COVID-19 patients. In addition, 23.5% had hemorrhagic CVD, and six patients with LVO developed hemorrhagic transformation. Conclusion: Acute CVD among patients with COVID-19 was common in our study. LVO was the commonest. Hypertension, IHD, and anemia are the most common risk factors and could contribute to the worsening of clinical presentation. Comorbidities were common among patients with CVD, although a large number had elevated liver enzymes and creatinine that were partially due to COVID-19 infection itself. The current results begin to characterize the spectrum of CVD associated with COVID-19 in patients in Upper Egypt. Registration ID: The ID number of this study is IRB no: 17300470.

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.

The Effect of 20 Hz versus 1 Hz Repetitive Transcranial Magnetic Stimulation on Motor Dysfunction in Parkinson's Disease: Which Is More Beneficial?

BACKGROUND: There is evidence that both high and low frequency rTMS may have therapeutic effects on motor performance of Parkinson's disease. OBJECTIVE: The aim of the study was to conduct the first direct comparison of the two approaches. METHODS: 52 PD patients were randomly classified into two groups. The first group received 20 Hz and the 2nd group received 1 Hz rTMS with a total of 2000 pulses over M1of each hemisphere for ten days. Effects were assessed with the Unified Parkinson's Disease Rating Scale part III (UPDRS), Instrumental Activity of Daily Living (IADL), and a self-assessment score (SA) before, after the last session, and one month later. Cortical excitability was measured before and after the end of sessions. RESULTS: There was a significant improvement on all rating scales after either 1 Hz or 20 Hz rTMS, but the effect persisted for longer after 20 Hz (treatment X time interaction for UPDRS and IADL (P = 0.075 and 0.04, respectively). Neither treatment affected motor thresholds, but 20 Hz rTMS increased MEP amplitude and the duration of transcallosal inhibition. In an exploratory analysis, each group was subdivided into akinetic-rigid and tremor dominant subgroups and the effects of 1 Hz and 20 Hz treatment recalculated. There was weak evidence that patients with an akinetic-rigid presentation may respond better than those with predominant tremor. CONCLUSION: Both 20 Hz and 1 Hz rTMS improve motor function in PD, but 20 Hz rTMS is more effective.

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.

Clinical impact of SNP of P53 genes pathway on the adult AML patients.

INTRODUCTION: Acute myeloid leukemia (AML) is a highly heterogeneous disease, with biologically and prognostically different subtypes. AIM: To study the impact of p53, p21, and mdm2 gene polymorphisms on the clinical outcome in adult AML patients treated at the National Cancer Institute (NCI) - Cairo University. METHODS: Forty-eight adult AML patients presented to the Medical Oncology Department, NCI, from April 2010 till November 2011. Clinical data and bone marrow samples were obtained. Molecular genetic analysis involving P53, MDM2, and P21 single-nucleotide gene polymorphisms was done using polymerase chain reaction-restriction fragment length polymorphism coupled analysis. RESULTS: The mean age was 35.7 years. After a median follow-up period of 12 months, 28 patients (58.4%) achieved complete remission (CR) and the overall survival (OS) was 8.7 months. Patients with homozygous Arg/arg at codon 72 of P53 had a better median OS months than Arg/Pro and Pro/Pro (13.4 vs. 8.4 vs. 1.5 months, respectively; P = 0.045). P53/p21 combination had a better median OS and disease-free survival (DFS) of 12.1 and 13.7 months for wild type cases (GG + Ser/ser) and 20.3 and 20.7 months for patients with either variant genes (GC + Ser/arg) compared with 1.1 and 1.9 months for patients with both variant genes (CC + arg/arg), (P = 0.037 and 0.004). The presence of wild genotype of either P21 or MDM2 may abolish the effect of P53 homozygous variant genotype on the OS. Neither p21nor mdm2 polymorphism alone showed an impact on OS or DFS. CR was not affected by any of the three gene polymorphisms. CONCLUSION: The p53 pathway gene polymorphisms may affect the OS of adult AML patients.

Serum indolamine 2,3 dioxygenase as a marker in the evaluation of allergic rhinitis.

BACKGROUND: Allergic rhinitis occurs on exposure to a known allergen and is correlated with a positive skin test and physical examination results. Tryptophan is a substrate of many important proteins, e.g., indolamine 2,3 dioxygenase (IDO). IDO, an immunomodulator, is a metabolic enzyme induced by immune activation. It has a significant role in allergic reactions. T-helper 2 cell is proposed to affect the expression of IDO. AIM: To evaluate IDO levels in patients with allergic rhinitis compared with controls and its relationship to the severity of allergic rhinitis. METHODS: This case-control study included 20 patients who were atopic and with allergic rhinitis who attended the allergy clinic of Ain Shams University Hospitals. Twenty age- and sex-matched patients who were not atopic were included as controls. An allergic rhinitis diagnosis was made according to the Allergic Rhinitis and its Impact on Asthma document. Complete history taking, physical examination, skin-prick test, complete blood cell count, erythrocyte sedimentation rate, total serum immunoglobulin E (IgE), IDO concentration, and nasal smear for eosinophils were done for the patients. RESULTS: There was a significant increase in IDO levels in allergic rhinitis in comparison with subjects without allergy (p < 0.001). IDO was positively correlated with total IgE levels (p < 0.037). There was an insignificant relationship among IDO levels and age, sex, duration of the disease, severity score, nasal and blood eosinophilia, and number of positive allergens. CONCLUSION: IDO plays an important role in patients with atopic symptomatic allergic rhinitis, especially with increased levels of IgE. There is no relationship between IDO levels and severity of disease.