The role of brain magnetic resonance imaging on the timing of antiepileptic drugs withdrawal following mesial temporal lobe epilepsy surgery

Objectives:To assess the influence of magnetic resonance imaging (MRI) brain findings on the timing of antiepileptic drugs (AEDs) withdrawal following anterior temporal lobectomy (ATL) in patients with mesial temporal lobe epilepsy (MTLE).Methods:We conducted a retrospective chart review at King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia from Jan, 2004 – Dec, 2017 of patients with MTLE who underwent ATL and included patients who had a minimum of 2 years of follow-up. We evaluated the association between the time required to start tapering and discontinuing AEDs after ATL in patients with Engel class I outcomes and their preoperative brain MRI.Results:We studied 64 patients who underwent ATL. The majority of patients (63%) had hippocampal sclerosis (HS) on histopathology. Following ATL, the mean time to start tapering AEDs was 10 months and AEDs were discontinued at a mean of 48 months. Abnormal brain MRI was observed in 53 (83%) patients, with findings suggestive of mesial temporal sclerosis (MTS) accounting for 75% of these abnormalities. The presence of any MRI abnormality was associated with a 10-month earlier tapering of AEDs (p<0.01), and an 18-month earlier complete withdrawal of AEDs (p<0.01). The odds of being seizure-free within the first year were higher if MTS was present in the brain MRI (adjusted OR=16). Similarly, this was associated with seizure freedom after the first year (adjusted OR=14.8, p<0.01). The presence of unilateral temporal IEDs on preoperative EEG were also associated with earlier tapering and discontinuation of AEDs as well as a seizure-free state after ATL surgery (OR=8.5 and 4.2, for the first and second year respectively, p<0.01).Conclusion:Patients with abnormal MRI findings and unilateral IEDs had earlier tapering of AEDs with an overall shorter AED discontinuation plan. Moreover, the presence of MTS on MRI, along with unilateral IEDs, were predictors of seizure freedom following ATL.

Anterior temporal lobectomy (ATL) is the standard treatment for medically refractory mesial temporal lobe epilepsy (MTLE), achieving seizure remission in approximately 70% of patients. ^1-3 However, the feasibility and timing of antiepileptic drug (AEDs) withdrawal after ATL are debatable. ⁴ The need for AEDs withdrawal stems from the adverse effects following long-term use, ^5,6 difficulties in maintaining compliance, and their high cost. ^7,8 Moreover, AEDs withdrawal following successful ATL is generally considered safe. ⁴ There are no evidence-based guidelines for managing AEDs withdrawal after resective epilepsy surgery. ^9,10 Moreover, few prospective and retrospective studies have assessed postoperative AEDs management exclusively in patients with MTLE. ^4,11-13 Hence, the timing of AEDs withdrawal after temporal lobectomy is controversial. ^12,14,15 The difficulties faced are how to taper AEDs, how soon it is safe to taper, which clinical profiles favor tapering, and what is the optimal time to start the tapering process. Predicting successful AEDs withdrawal following ATL has been examined in a few studies; however, the results were inconsistent. ^9,12,16-18 In one study, brain magnetic resonance imaging (MRI) findings were associated with seizure outcomes following ATL with successful AEDs discontinuation. ¹² The MRI can detect brain abnormalities, predict postoperative seizure, and AEDs freedom ² Despite this, data are lacking regarding the role of MRI in determining the time to start tapering AEDs postoperatively, as well as the time until AEDs discontinuation in those who do not require postoperative AEDs treatment. These data are essential for establishing guidelines that could assist clinicians with AED management following ATL.We aimed to assess the role of brain MRI in planning the tapering of AEDs and determining when to discontinue AEDs in patients with MTLE following ATL. We also evaluated seizure outcomes in patients with a minimum of 2 years of postoperative follow-up.     

Unique challenges in the management of a Giant retroperitoneal Schwannoma associated with vertebral body destruction and spinal canal invasion

Retroperitoneal schwannomas are rare, and giant lesions associated with osteolysis are unique clinical entities for which management guidelines are lacking. Herein, we present our experience with treating a large paraspinal retroperitoneal schwannoma, compare it with previously reported cases, highlight the challenges faced with its management, and propose a treatment plan. A 56-year-old female patient presented with back and left leg radicular pains. Contrast-enhanced CT and MRI scanning and histological analysis confirmed the presence of a giant retroperitoneal schwannoma causing near-complete destruction of the fourth lumbar vertebral body and spinal canal invasion. The tumor was totally removed by a two-step operation with no adverse consequences. The patient recovered well and remained in good clinical and radiological status 9 months post-surgery. Therefore, retroperitoneal schwannomas causing bone destruction and spinal canal invasion are best treated through a combined posterior-anterior approach.

Schwannomas in the retroperitoneal space are rare; they account for less than 3% of all schwannomas.¹ Retroperitoneal schwannomas (RSs) are often benign (99%) and giant-sized because the expansile retroperitoneal space allows the tumor to enlarge even before presenting; therefore, one-third of RS cases are incidentally discovered.^2,3 The presenting symptoms are usually nonspecific: abdominal pain and distension are the most typical presenting features followed by back pain and radicular leg symptoms.^2,4Paraspinal retroperitoneal schwannomas that erode the spinal column are exceedingly rare with only four cases previously reported in the recent 15-year English literature.^1,3-5 They are unique clinical entities because of their rarity, presenting features, and complexity of management. The challenges in managing RS include ensuring a correct preoperative diagnosis, achieving an oncologic resection with no vascular or neurological injury, and maintaining the spinal column stability postoperatively. Therefore, the surgical resection of sizable RS poses a tremendous challenge and effective surgical management guidelines are lacking.In this paper, we present our management strategy for a massive RS that caused almost the complete lysis of the fourth lumbar (L4) vertebral body resulting in spinal canal invasion with severe neural compression. We propose a practical surgical management plan based on the lessons learned from this case and our updated review of previously reported cases.     

Decompressive craniectomy is a life-saving procedure in malignant MCA infarction

Objectives:To investigate the indications, timings, and outcomes of decompressive craniectomy (DC) performed for malignant middle cerebral artery (MCA) infarctions at our tertiary care center.Methods:This retrospective case series involved patients who underwent DC for malignant MCA infarction at King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, between January 2012 and December 2018. Demographic, clinical, and radiological data were collected, and stroke- and surgery-related complications and discharge outcomes were assessed.Results:Eighteen patients (mean age: 50±10 years), of whom 13 (72%) were men, underwent DC during the study period. Of the patients, 9 (50%) had severe stroke (NIHSS 16–25), 10 (56%) had right MCA infarction, and 11 (61%) received either intravenous thrombolysis or endovascular thrombectomy or their combination. Indications for surgery included clinical deterioration as seen in 16 (89%) patients, ipsilateral pupillary dilatation as seen in 11 (61%) patients, and signs of raised intracranial pressure in 6 (33%) patients. Surgery was performed within 48 h in 14 (78%) patients. The mean Intensive Care Unit stay was 15±7 days. Seven (39%) patients were discharged home and 3 (17%) were transferred to an inpatient rehabilitation unit, and 2 (11%) patients died. All patients had stroke-related complications; one (6%) patient developed cerebrospinal fluid leak, 3 (17%) had sunken skin flap syndrome and wound infection each, and 2 (11%) developed epidural hematoma.Conclusion:The DC was life-saving in the our patients with malignant MCA infarction. Most of the patients had surgery within 48 hours. More than one-third of the patients were discharged home, while mortality occurred in only 2 patients. Moreover, stroke- and surgery-related complications were common in our cohort.

Stroke is one of the leading causes of death and adult disability worldwide.^1,2 The burden of stroke is increasing and is a significant challenge for health care systems across the globe.² Ischemic stroke due to occlusion of proximal middle cerebral artery (MCA), usually involve large portions of a hemisphere and may cause space-occupying cerebral edema, leading to rapid neurological deterioration and cerebral herniation.^2,3 Nearly 35 years ago, Hacke et al⁴ coined the term “malignant” for acute and complete MCA territory infarction involving a space-occupying cerebral edema and subsequently a considerably rapid neurological deterioration and herniation. Malignant MCA infarction involves more than 50% of and often the entire MCA territory.^3-5 In the early phase of malignant MCA infarction, cytotoxic edema develops followed by the development of vasogenic edema.³ Approximately 1-10% of all MCA strokes can turn into malignant MCA infarction with a mortality risk of up to 80% within the first week.^2,3 Acute brain swelling occuring within 48 hours results in elevated intracranial pressure (ICP) or brain herniation, which in turn leads to the deterioration of consciousness or death usually within the first week.^2,3,6 The clinical predictors of malignant transformation include high NIHSS (National Institute of Health Stroke Scale) score, young age, female gender, as well as history of hypertension, ischemic heart disease, and congestive heart failure.^2,6 The radiological predictors of malignant transformation are >66% perfusion deficit, >50% involvement of MCA territory on initial CT scan, and combined involvement of internal carotid artery and MCA, among many others.⁶Control of ICP remains an important challenge in patients with severe post-stroke or post-traumatic brain edema. The medical management for raised ICP include head-of-bed elevation, hyperventilation, osmotic therapy, and sedation.^6,7 Although osmotic therapy has failed to improve treatment outcomes, it can be used to bridge time until definitive surgical treatment can be performed.³ Systemic hypothermia in raised ICP due to malignant MCA infarction has been associated with multiple complications without any clear benefit on outcome.⁶Trephination, an ancient treatment method of brain diseases, may be the earliest form of decompressive craniectomy.⁸ Decompressive craniectomy (DC) was described more than a century ago, but it did not receive acceptance for most of the 20th century.^8,9 One of the earliest reports on DC for malignant MCA infarction was published in 1951.¹⁰ A pooled analysis of three randomized trials conducted in the early part of this century showed for the first time the benefit of early DC in malignant MCA infarction.¹¹ These 3 initial European trials, namely, DECIMAL, DESTINY, and HAMLET, were the first to prove that DC was associated with decreased mortality and with the increased number of patients with favorable outcome.^11-14 The mortality rates decreased from 78% in historical controls to as low as 16% in surgically treated patients, with the number needed to treat (NNT) as low as 2 for survival with mRS (modified Rankin Scale) of ≤4.¹³The DC involves the removal of a part of the skull referred to as bone flap; along with opening of dura to accommodate brain swelling.^8,9 In malignant MCA infarction, only unilateral decompression, also termed as decompressive hemicraniectomy, is performed.⁸ The DC allows an edematous brain tissue to herniate outside, thus preventing neuronal damage in other regions of the brain.^2,8 A meta-analysis of 8 randomized trials and 4 observational studies confirmed the mortality benefit of DC in malignant MCA infarction.⁷ Patients and caregivers were satisfied with their QALY despite the disability of the patients; however, professionals did not consider surgery as favorable treatment due to the high disability rates post-surgery.⁷There is one prior published study about decompressive craniectomy in malignant MCA infarction from Saudi Arabia describing 6 patients undergoing DC.¹⁵ Our study aimed to investigate the indications, timings, and outcomes of DC performed for malignant MCA infarctions at our tertiary care center. We believe that this work will add to the limited literature about this condition from the region.     

Prevalence and biopsychosocial factors associated with treatment adherence among people with epilepsy in a tertiary care hospital in Riyadh,Saudi Arabia

Objectives:To identify the magnitude of treatment adherence among people with epilepsy (PWE) and the impact of sociodemographic, medical and psychosocial factors on treatment adherence.Methods:A quantitative cross-sectional observational study was performed based on data collected from adult patients attending the epilepsy clinic, King Saud University Medical City, Riyadh, Saudi Arabia. Patients completed paper-based questionnaires including a sociodemographic, cultural, psychiatric history and medical history sections. In addition to that we evaluated treatment adherence by visual-analogue scale (VAS), depressive symptoms by PHQ-9, anxiety symptoms by GAD7, physical symptoms by PHQ-15, attachment style by ECR16 and cognitive impairment by MOCA.Results:A total of 207 patients participated, with a mean age of 34 years;.53.6% were female. The mean patient-reported adherence to their treatment regimen was 81.6%±18.4%. Univariate analysis revealed statistically significant negative associations between depression, anxiety and physical symptoms and treatment adherence. However, multiple linear regression analysis only showed physical symptoms to be a significant predictor for epilepsy medication adherence.Conclusion:Somatic (physical) complaints could be important predictors of treatment adherence in (PWE). This study is one of the first to suggest the importance of targeting physical symptoms in screening and intervention approaches to improve Antiepileptic drugs (AEDs) adherence.

Epilepsy is one of the most common chronic serious neurological diseases and affects approximately 50 million people of all ages worldwide. ¹ The estimated median prevalence of epilepsy in Arab countries is 2.3/1,000 (varying from 0.9–6.5/1,000), which is just within the range found in Europe, North America, Australia, and Asia. ² In Saudi Arabia, the prevalence of active epilepsy is 6.54/1000 population. ³ According to global and local studies, most cases of epilepsy are idiopathic, though it may be caused by cerebrovascular accidents, head trauma, cerebral palsy and CNS infection. ^1,4 The overall mortality rate for (PWE) is increased by two- to threefold compared with the general population. ^1,5,6 In addition, there are high rates of psychological conditions such as depression and anxiety among (PWE). ^7-10 Patients with mood disorders are more likely to be nonadherent with regard to medication. ^8,11–13 The World Health Organization defines medication adherence as the extent to which a patient’s behavior, in terms of taking medications, following a diet, and/or executing lifestyle changes, corresponds with agreed recommendations from a health care provider. ¹⁴ Anti-epileptic drugs (AEDs) are the main therapy for epilepsy to prevent seizures. ¹⁵ Indeed, up to 70% of children and adults with epilepsy can be successfully treated with AEDs. ¹ However, the prevalence of significant medication nonadherence in epilepsy has been reported to vary between 26% and 79%. ¹⁶ A cross-sectional study performed locally in Riyadh, Saudi Arabia, at King Fahad Hospital found that 48.7% of patients were nonadherent regarding anti-epileptic medication. In this study, adherence was assessed by asking patients whether they ever missed or stopped their medications, with the most common factor for nonadherence being forgetfulness. ¹⁷ In another local study performed among adolescents with epilepsy conducted cross-sectionally at Riyadh National Hospital in Saudi Arabia, 38.3% were antiepileptic drugs nonadherent, and the most important factors affecting adherence to prescribed medication were the age of the mother, number of family members, number of administered drugs and seizure frequency. ¹⁸ In general, the risk of subsequent seizures among nonadherent patients may increase by 21%. ¹⁹ Nonadherence is also associated with an increased likelihood of hospitalization and emergency room admission and with an over threefold increased risk of mortality compared to adherence. ^20,21 Depression, stress and anxiety are all associated with reduced antiepileptic drug adherence. ^{8,11–13,22–24} Additionally, the results of another study showed that depression measured by another scale (NDDI-E) correlated with an increased risk of AED nonadherence, which led to the same result. ²⁵ Conversely, perceived social support correlated positively with adherence. ²³ In another study, however, neither depression nor family support were associated with adherence. ²⁶ Nevertheless, these studies did not discuss the correlation between attachment style and cognitive function with treatment adherence in patients with epilepsy (PWE). However, multiple studies conducted on other diseases showed an association between attachment style especially avoidance, and reduced adherence to medical treatments. ^27–29 A study at King Khalid University Hospital in Saudi Arabia has addressed the psychosocial predictors of treatment adherence in another neurological disorder, multiple sclerosis, and found that 79.47% of patients were adherent to treatment, with the most significant factor associated with nonadherence being cultural beliefs. ³⁰ To date, there is a lack of research about the psychosocial aspects of epilepsy in Arab countries. ³¹ In fact, none of the local studies we found mentioned psychosocial predictors related to adherence among patients with epilepsy. Hence, this cross-sectional study aims to identify psychosocial predictors, specifically depression symptoms, anxiety symptoms, cognitive impairment, attachment style and cultural beliefs, for treatment adherence among (PWE). Addressing psychosocial problems may help to optimize care for these patients. ³² Overall, identifying barriers to AED adherence is imperative to help practitioners who are developing appropriate strategies to improve adherence rates. ^20,24      

Predictors of citation rates for research publications in Neurosciences

Objectives:To identify the predictors of citation rates for research publication in Neurosciences.Methods:All original articles including meta-analyses (MAs) and systematic reviews (SRs) that were published in Neurosciences during 2011 to 2019 were reviewed. The impact of several predictors on citation rates was assessed using correlation coefficient and mean difference tests.Results:This study examined 231 articles. The mean article citation number was 11.6. The correlation analysis showed a significant association between citation rates and duration from publication in years (p<0.0001), sample size (p<0.0001), study design (p=0.0353), and level of evidence (LOE) (p=0.03). The comparative analysis showed significantly more citations for articles that were published 6-10 years ago (p<0.0001), had a sample size >91 (p=0.0359), were randomized controlled trials (p=0.0353), MAs and SRs (p<0.0001), and level of evidence (LOE)-I (p=0.0004). Retrospective case series had significantly lower citations. The higher and lower citation numbers for publications from Iran and rehabilitation, respectively, may have been influenced by the duration from publication.Conclusion:The most significant predictors of citation rates for Neurosciences publications were the age of articles, population size, study design, and LOE. Awareness of the predictors of citation rates may help researchers enhance the academic impact of their work.

The number of citations an article receives, also referred to as the citation rate, is arguably the most important indicator of its impact and clinical significance. ^1,2 Identification of the predictors of citation rates is useful for researchers and journals in order to boost the impact of their work. ¹ This topic has been the subject of several studies in recent years. Most such publications have focused on identifying the predictors of citation rates in the literature relating to certain fields, including neurosurgery, ² spine, ³ orthopedics, ⁴ neurosciences, ⁵ plastic surgery, ⁶ urology, ⁷ radiology, ⁸ and glioblastoma multiforme trials. ⁹ Several variables were identified as potential citation rate predictors. Their significance however, differed between various reports. These included sample size, study design, level of evidence (LOE), topic, journal IF, field, and publishing country, as well as the number of authors, institutions, countries, and references listed on the paper. ^1-4,6-9 In a recent study, ⁵ several bibliometrics besides journal IF were identified as predictors of citation counts in neurosciences journals. These included the Eigenfactor score, cited half-life, immediacy index, and number of articles. Furthermore, in the era of digitization, open access, and social media activities are increasingly recognized as drivers of citation activities. ¹ Neurosciences Journal, which is referred to as Neurosciences (Riyadh) in PubMed and will heretofore be referred to as Neurosciences in this article, is an open access, peer-reviewed, quarterly publication that was launched in 1996. ¹⁰ The journal is published by the Armed Forces Hospital, Riyadh, Kingdom of Saudi Arabia (KSA). ¹⁰ The Scimago Journal and Country Rank (SJR) web site, ¹¹ ranked KSA as fortieth in the world and fourth in the Middle East based on the total citations of its clinical neuroscience literature during 1996- 2020. However, to date, the factors that influence citation rates have not been addressed in Neurosciences or in any other Saudi medical journal. The objective of this study is to identify the predictors of citation rates for Neurosciences publications. It is hoped that the awareness of the factors that impact citations will help researchers enhance the impact of their work.     

Early seizures in stroke – frequency,risk factors,and effect on patient outcomes in a tertiary center in Saudi Arabia

Objectives:To determine the frequency, risk factors, and outcomes of Early seizure (ES) after stroke in a Saudi cohort.Methods:A retrospective study was conducted in King Abdulaziz Medical City, Riyadh, KSA. All stroke patients whether they had first or recurrent stroke were included from February 2016 to December 2017. Data were analyzed using the SAS software version 9.4.Results:Out of 665 patients, 456 (68.6%) were males and 564 (85.2%) were Saudis; the cohort’s mean age was 60.6±12.6 years. Fifty-one (7.7%) patients had ES, which were more common in women (p=0.0123). Loss of consciousness (p=0.0402) and confusion (<0.0007) were associated with ES, whereas unilateral weakness (p=0.001) and unilateral numbness (p=0.0317) at presentation decreased the risk of ES. Vascular risk factors did not differ between patients with and without ES. Hemorrhagic stroke was associated with ES (p=0.0054), whereas patients with small vessel disease were less likely to develop ES (p=0.0013). Patients with ES had more severe stroke (NIHSS >5) (p=0.0139), more ICU admissions (49% vs. 26.2%; p=0.0005), longer length of hospital stay (44.9 days vs. 24.9 days; p=0.0018), higher rates of stroke-related complications (e.g. recurrent stroke, pulmonary embolism, hospital acquired infections, and need for tracheostomy and gastrostomy tube placement) (p≤0.0001), and were likely to be more severely disabled defined as mRS 3–5 at discharge (47.7% vs. 40.8%; p=0.0055) or to die in hospital (11.8% vs. 4.6%; p≤0.0001).Conclusion:The ES after stroke were common in our cohort. Increased stroke severity and confusion were independent predictors of ES. The ES were associated with higher rates of in-hospital complications, longer length of hospital stay, and worse outcomes at discharge.

Stroke is one of the common causes of symptomatic seizures in the elderly. Post-stroke seizures (PSS) are commonly classified into early seizures (ES) and late seizures (LS). ¹ No specific cut-off point that delineates ES has been agreed upon, but most studies arbitrarily define ES as those that occur within 7–14 days of incident stroke. ^1-2 The PSS occurring beyond this period are considered LS. The incidence rate for ES after stroke is not well established, although it has been reported to be 2%–33%. ^2,3 A recent meta-analysis has found that ES incidence after ischemic stroke is 3.3%, whereas the LS incidence rate was found to be 18 per 1000 person-years. ¹ A study investigating seizures that occurred within 24 h of stroke onset has found an incidence of 3.1% in more than 6,000 stroke patients. ³ Not all patients with PSS develop epilepsy. Approximately 2-4% of patients develop epilepsy after stroke. ⁴ Data on the risk factors for ES after stroke are inconsistent. In some studies, cardioembolic stroke, cortical location of stroke, hemorrhagic transformation of ischemic stroke, increased severity of stroke, and history of coronary artery disease or atrial fibrillation were found to be the predictors of ES after stroke. ^2,4-5 The ES after stroke are associated with increased morbidity and mortality, and can affect the functional independence of stroke patients, resulting in poorer quality of life, as well as in increased resource utilization. ^3-6 However, evidence-based data on PSS and guidelines on PSS management remain lacking. ⁶ The PSS are not uncommon and are broadly classified into ES and LS. Not all patients with ES develop post-stroke epilepsy. ⁶ The pathophysiological mechanisms underlying ES and LS are widely different. Having a specific time window to define ES from LS is crucial, as this may help in predicting post-stroke epilepsy. In the acute phase of stroke, ionic shifts, excitotoxicity neurotransmitters, metabolic dysfunction, and changes in coagulation cascade can all contribute to the early onset of seizure after an ischemic event. ^7-8 By contrast, LS results from persistent structural changes and gliosis that occur in the late phase of stroke, causing disruption in neuronal firing, circuit dysfunction, and eventually epileptogenic changes. ^7-8 The PSS has been studied in different populations; considering the observed variations in incidence, risk factors, and outcomes of PSS, we find it important to investigate this condition in the Saudi population. Our study aimed to determine the frequency of post stroke seizures in our population, and to identify the predictors of ES. It also looked at the outcome of these patients. To the best of our knowledge, this is the earliest study to report data on ES after stroke in a Saudi cohort, and it may be useful in planning future large-scale studies on ES prevention and management.     

Invasive aspergillosis of the central nervous system in immunocompetent patients in Saudi Arabia: Case series and review of the literature

Objective:Invasive aspergillosis of the central nervous system in immunocompetent patients is a rare disease. We present in this study three cases that were treated in our centre and reviewed the results of similar studies from Saudi Arabia.Methods:We retrospectively reviewed all cases of invasive aspergillosis of the central nervous system (CNS) that were treated in our hospital in the last 10 years. We also reviewed the literature for any similar series published from Saudi Arabia.Results:We had three cases treated in our centre and we also found three similar case series in the literature. Total number of cases, including our series was 28, age range from 17 to 66, 10 men and 18 women. The source of infection was nasal sinuses in all cases. Initial presentations were variable and included headache (80% of cases), proptosis or diplopia (50% of cases), seizures (20% of cases), cranial nerve palsies (18% of cases) and acute deterioration in level of consciousness (18% of cases). All patients underwent surgery followed by long course of antifungal treatment. Clinical outcome was reported as cured or no recurrence in 13 cases (47%).Conclusions:Invasive aspergillosis of CNS is a rare disease in immunocompetent patients. Despite treatment prognosis remains unfavourable in many cases.

Invasive aspergillosis (IA) is the most common invasive mould infection, particularly among immunocompromised patients. Aspergillus fumigatus accounts for almost 90% of infections in humans. However, other Aspergillus species, such as A. flavus, A. terreus and A. niger, were more commonly isolated in cases involving immunocompetent patients.¹ Cases of of IA of the central nervous system (CNS) infections in immunocompetent patients are rare and mainly reported in tropical and subtropical geographic areas, including Southeast Asia and the Middle East.²The most common primary infection site of IA of CNS in immunocompetent patients is usually the paranasal sinuses (sinus aspergillosis). From there, the infection can invade the skull base and orbit and then locally infiltrate the intracranial cavity. This invasion can lead to different pathological changes in the CNS, including granuloma or abscess formation, meningeal inflammation and cerebrovascular insults (ischaemic stroke, or intracranial haemorrhage due to vascular thrombosis, or mycotic aneurysm).^3,4Clinical presentations of IA of CNS can be indolent or acute with variable symptoms, depending on the location of the infection in the CNS and the ensuing pathological changes.² The diagnosis of IA of CNS is usually difficult, since clinical presentations can vary, and radiological findings may mimic invasive skull base lesions, high-grade brain tumours, and other causes of CNS infections or abscess.^2-4 Sampling of the infected area (sinuses or intracranial extension) for bacterial, mycobacterium, fungal and histopathology are essential for diagnosis.² When diagnosis of IA of CNS is confirmed, surgical excisions of infected tissue of the paranasal sinuses, skull base bone and brain abscesses/granuloma should be performed when feasible.⁴ Following surgery, an extended course of antifungal therapy should be prescribed. However, initiation of empirical antifungal therapy on suspicion is recommended due to high mortality.¹ Prognosis remains poor in a the majority of IA of CNS cases due to difficulty in achieving a complete resection due to the location of the brain invasion and involvement of intracranial vessels. In addition, some antifungal medications have limited ability in cerebrospinal fluid penetration.^2,4In this paper, we present a case series of IA of CNS in immunocompetent patients from our centre. We have also searched the literature for similar studies of the disease in Saudi Arabia in the last four decades. The overall aim was to review the clinical presentations, radiological findings, pathological features, mycology studies, treatment and clinical outcomes of IA of CNS in Saudi Arabia.     

Efficacy and safety of rituximab in patients with multiple sclerosis: An observational study at a tertiary center in Makkah,Saudi Arabia

Objectives:To assess the efficacy and safety of rituximab for multiple sclerosis (MS) treatment in terms of reduction in clinical relapses, magnetic resonance imaging (MRI) activity, Expanded Disability Status Scale (EDSS) score and adverse events.Methods:This is a retrospective cross-sectional study conducted at King Abdullah Medical City, from January 2017 to August 2021, involving patients with MS given rituximab, with 1-year follow-up. Clinical parameters were noted pre- and post-treatment to determine efficacy; adverse events were noted to analyze safety. A paired samples t-test was used to compare responses pre- and post-treatment. A p-value<0.05 was considered significant.Results:Among 31 patients, 6 (19.4%) had progressive MS, and 25 (80.6%) had relapsing-remitting MS (mean disease duration=8.12±5.65 years). The annual relapse rate reduced from 1.67±0.97 to 0.06±0.25 (p<0.001), the EDSS score from 3.16±2.14 to 2.80±2.28 (p=0.141) and the MRI activity score from 1.84±1.03 to 1.03±0.18 (p<0.001). Only one patient had enhancing lesion activity post-treatment. The commonest side effect was urinary tract infection (25.8%). Only 2 patients discontinued the drug.Conclusion:Rituximab is an efficient drug in reducing the annual relapse rate and MRI activity of patients with MS, with few tolerable side effects not leading to drug discontinuation or any lethal outcome.

Multiple sclerosis (MS) is a condition of the central nervous system carrying a chronic course and having autoimmune etiology. The disease has a prevalence of 40.4 per 100,000 people in Saudi Arabia. ¹ MS can have a relapsing-remitting course which begins with an acute attack and is then followed by full or partial recovery (also known as relapsing-remitting MS [RRMS]). Alternative clinical presentation of MS is characterized by progressive neurological worsening without any acute attack (also known as primary progressive MS). Secondary Progressive MS is another advanced stage in the course of disease where disability worsens gradually without a new relapse. ^2,3 The disease process was earlier thought to be mediated by T cells, but research has brought forth the suggestion that B cells, too, do play a role in the pathological process. ⁴ It is now well understood that antigen presentation by B cells is a necessary step in the pathogenesis of the immune-mediated process against the glycoprotein myelin found in central nervous system. ⁵ Therapies targeting T cells (for example, interferon-beta and natalizumab) have been traditionally used for MS, but not all patients improve despite treatment compliance. Moreover, interferon causes a myriad of highly stressful side effects, and natalizumab, in addition to causing minor adverse effects, has a risk of causing a serious condition like progressive multifocal leukoencephalopathy (PML). ⁶ New therapies that target B cells are increasingly being investigated. Rituximab (RTX) is one such drug that targets CD 20 expressing B cells and also reduces T cells. The drug has shown promising results in the treatment process. ^7,8 The safety of RTX usage is established by Class IV evidence. ⁹ Phase 2 trials have shown that RTX reduces magnetic resonance imaging (MRI) inflammatory lesions by up to 88% in the patients of MS. ^10,11 Off-label RTX usage in MS is further supported by several trials. ^11,12,13 One such study showed MRI activity reduce from 88% to 8.3% in only a year and annual relapse rate reduce from 0.75 to 0.36 with the use of RTX. ¹³ The common side effects of RTX usage in patients with MS include infections (36%), with urinary tract infection being the most common, and infusion reactions (8%). This CD 20 targeting drug also increases the risk for fungal infections. ^14,15 Studies comparing the efficacy of RTX to conventional therapies have concluded that RTX has better performance in MS, especially in newly diagnosed cases of RRMS. ¹⁶ Our aim was to study the reduction in MRI inflammatory lesions, disability changes and relapses in patients with MS presenting at King Abdullah Medical City as a result of RTX therapy.     

Investigation of inflammation related gene polymorphism of the mannose-binding lectin 2 in schizophrenia and bipolar disorder

Objectives:To investigate the association between mannose-binding lectin 2 (MBL2) codon 54 polymorphism and clinical features of patients diagnosed with schizophrenia (SCZ) or bipolar disorder (BD).Methods:One hundred and eighteen patients with SCZ, 100 patients with BD, and 100 healthy volunteers were included in the case-control study. The patients consecutively admitted to the outpatient clinic in December 2017-May 2018 and were evaluated with some scales for clinical parameters. Polymerase chain reaction and RFLP were used to determine MBL2 polymorphism in DNA material.Results:The MBL2 gene polymorphism distributions in SCZ or BD patients were significantly different from the control group. The heterozygous genotype percentages were significantly higher in the control group than in the SCZ or BD patients (OR: 0.450; 95% Cl: 0.243-0.830; p=0.010; OR: 0.532; 95%Cl: 0.284-0.995; p=0.047, respectively), and there were statistically significant differences in the MBL2 polymorphism distributions between treatment-responsive SCZ or BD patients and treatment-resistant patients diagnosed with SCZ or BD. The heterozygous genotype percentages were also significantly higher in the treatment-responsive group than in the treatment-resistant group in SCZ or BD patients (OR: 7.857; 95% Cl: 1.006-61.363; p=0.023; OR: 8.782; 95% Cl: 1.114-69.197; p=0.016, respectively).Conclusion:The presence of a heterozygous MBL2 genotype seems to be favorable both in terms of the absence of SCZ and BD in the healthy population and treatment response for Turkish patients.

Schizophrenia (SCZ) and bipolar disorder (BD) are chronic psychiatric disorders that cause substantial disruptions in psychosocial capacity and occur in approximately 1% of the world population.¹ Genome-wide association studies (GWAS) of Psychiatric Genomics Consortium for SCZ recognized more than a hundred common single nucleotide polymorphisms (SNPs) with minor individual effects presenting susceptibility to the SCZ.² A similar mega-analysis for BD, although including a more moderate sample, identified common risk variants specific to BD.³ The long-lasting alterations in gene expression patterns after environmental exposures imply that epigenetic mechanisms might also play a critical role in chronic psychiatric disorders.⁴ Again, previous researches have constantly reported shared genetic etiology between SCZ and BD. Researches showing the genetic overlap between SCZ and BD have improved from studying family and twin inheritance to determine genetic correlation and performing polygenic risk score analysis from GWAS data in large case-control samples.⁵ Despite these researches with large sample size, the cause of both disorders is still relatively unknown; recent studies have shown that uncontrolled activity of microglia and excessive inflammatory responses caused by pro-inflammatory cytokines are among the factors that play a role in the development of SCZ and BD based on genetic susceptibility.^1,6 A relationship between SCZ and many autoimmune diseases and an increase in the prevalence of an autoimmune disease occurrence by about 45% have been found. Moreover, infections of embryonic and early childhood periods lead to delays in fetal brain development and excessive synaptic pruning during adolescence, are among the possible risk factors of psychosis.^7,8 Systemic inflammation and central inflammation are thought to be associated with episodes, remission, and prognosis of BD. Neuroendocrine irregularities, neurotransmitter abnormalities, and glial cell dysfunctions cause plastic alterations in the mood-regulating brain areas. The high rate of comorbid autoimmune diseases also supports this claim.⁹Mannose-binding lectin (MBL) has a vital function in the innate immune system by stimulating the complement system’s lectin pathway. Therefore, it is the only collectin that binds to microorganisms, serves as an opsonin, promotes phagocytosis, and stimulates macrophages. MBL2 gene, which consists of 4 exons in the q11.2-q21 region of the long arm of chromosome 10, encoded MBL. Mutation at codon 54 follows in a replacement of glycine to aspartic acid (allele B), and the normal MBL2 allele is defined by allele A.^10-12 In heterozygous mutants, serum MBL decreases almost 10-fold, whereas, in homozygous mutants, the level decreases to an undetectable level. MBL deficiency is the most common immune defect in humans, affecting approximately 5-7% of individuals.¹³ A decrease in serum MBL level can cause recurrent spontaneous miscarriage,¹⁴ premature birth,¹⁵ and exacerbation of chronic diseases such as ischemic heart disease,¹⁶ and severe infections such as sepsis and systemic inflammatory response syndrome (SIRS).¹⁷ Besides, previous studies suggested that MBL plays an essential role in the pathogenesis of autoimmune diseases.^12,18 We believe that this is the first case-control study comparing MBL2 genotype distributions in patients with SCZ or BD according to treatment resistance, clinical characteristics, and scale scores in detail.Aims of the studyWe aimed to examine whether MBL2 codon 54 polymorphism was involved in the etiopathogenesis and treatment response of SCZ and BD compared with healthy controls.     

The effect of cervical mobilization on balance and static plantar loading distribution in patients with multiple sclerosis: A randomized crossover study

Objectives:To investigate the influence of repeated cervical mobilization (CM) on balance and plantar loading distribution in patients with Multiple Sclerosis (MS).Methods:A total of 12 individuals were included in the cross over study designed as a cross sectional. The study was carried out from October 2019 until July 2020. Individuals received traditional treatment (TM) and cervical mobilization treatments (CM) 2 days a week for 4 weeks in a different order by random method. It was treated with joint traction and sliding techniques. Soft tissue mobilization techniques for myofascial relaxation were applied for CM in addition to TM. Romberg test (RT), Sharpened Romberg Test (SRT), and Functional Reach Test (FRT) were used to balance the assessment. Plantar loading distribution was evaluated with Pedobarography. The maximum and mean pressure in the foot, the percentages of pressure values in the fore and rear of the foot, and percentages of the bodyweight discharge onto right feet and left feet were recorded.Results:The forefoot loading increased after treatment in the CM group (p<0.05). The duration of RT and SRT increased, and average pressure decreased in the cervical mobilization group (p<0.05). The body weight discharge onto right feet and left feet approached 50% after cervical mobilization (p<0.05).Conclusions:Cervical mobilization techniques can positively change the balance and plantar loading distribution compared to traditional treatment. Cervical mobilization applications could be used to support neurological rehabilitation.

Multiple sclerosis (MS) is a demyelinating, inflammatory, chronic, and neurodegenerative central nervous system (CNS) disease.¹ Motor findings (spasticity, weakness), sensory findings (numbness, tingling, loss of sensation), balance and coordination problems, fatigue, visual dysfunction, cognitive disorder, bulbar symptoms (dysarthria, dysphagia respiratory problems), bladder-bowel dysfunction can be observed in patients.² Studies show that 80% of patients have different levels of sensory impairment.³ The sense of proprioception, which is part of the somatosensory system, has an important role in the regulation of the vestibular system. This sense is obtained from the receptors in the joints, muscles, tendons, and ligaments and constitutes the position perception of the extremities and the body. Proprioceptors present in different proportions in different body structures and tissues are especially rich in the cervical region.⁴ Studies have proved that different treatment methods such as vibration and Kinesio taping on the cervical region stimulate the proprioceptive system, and these methods improve visual and vestibular connections.^5-7 Another method that can be applied to activate the proprioceptive system in this area is cervical mobilization techniques.Manual techniques affect mechanotransduction, converting mechanical impulses into biological signals by myocytes and fibroblasts.⁸ Thus, silent gamma motor neurons are stimulated by inputs in muscle spindle afferents and smaller-diameter afferents.⁹ The cervical region is important for postural control, and cervical afferents provide input to cervicocollic, cervicooculler, and tonic neck reflex. So that postural stability, as well as head and eye movements, are controlled and maintained.¹⁰ Muscle spindles in the cervical region, especially in the suboccipital area are found in high densities.¹⁰ The application of manual therapy techniques to the cervical region increases motor control by increasing the proprioception transmitted from the vertebra segment to the central nervous system.¹¹ These techniques also increase short-term motor neuron activity, resulting in increased performance in activities related to proprioception.¹² It was known that the effects of mobilization techniques with neurophysiological effects on balance development, but studies investigating the effect of cervical mobilization are limited to orthopedic cases or healthy persons.^9,13Moreover, many studies in literature focused that manual therapy techniques diminish pain, improve range of motion, quality of life in groups without neurological disorders.^14-16 In other words, both the sample variety in terms of disorders and the treatment effects were examined in a narrow range.The stimulation of the cervical region rich in proprioceptors increases somatosensory system activity so that it contributes to the improvement of balance. Balance and gait problems were frequently seen in MS patients.¹⁷ The foot, which carries the whole body weight and plays an important role in locomotion, provides a base of support for balance.¹⁸ Balance and plantar pressure were investigated together in our study since the sensorial inputs for balance are obtained from plantar pressure. In accord with the move, the base of support constantly changes during the walk, daily activities. As change base of support, plantar load distribution alters.¹⁸ Main plantar load on the forefoot has been associated with balance disorders and falls.¹⁹An individual can provide balance by using toe pressure to correct the many postural disturbances that are experienced in everyday life.¹⁸ In addition, the plantar sensation obtained from the forefoot with the loading is essential in the control of balance. Moreover, ıt determined reduced peak pressure under the metatarsal head because of spasticity in MS.²⁰ It is unknown how plantar pressure distribution changes with rehabilitation in MS patients.Based on this background, the literature supports the positive effect of cervical mobilization in neurological disorders. However, only one study investigated the effect of cervical mobilization in MS.²¹ Therefore, our study is planned to investigate the effects of repeated cervical mobilization on balance and plantar pressure in MS individuals.     

The response patterns of infantile spasms to treatments in 156 patients: Hormonal therapy with intravenous synthetic ACTH appears promising

Objectives:To report the efficacy of intravenous (IV) synthetic ACTH (Tetracosactide) in the treatment of infantile spasms.Methods:This is a retrospective chart review of patients with a diagnosis of infantile spasms conducted at the Pediatric Department of King Abdulaziz Medical City (KAMC) in Riyadh, Saudi Arabia, from 01-01-2005 to 31-12-2019.Results:Of the 156 cases, 141 were treated initially with vigabatrin (VGB) with a complete response seen in 42(30%). Synthetic ACTH (Tetracosactide) IV injections were used in a total of 52 cases with response in 25(48%). Of the 35 cases which initially failed with VGB, 20(57%) responded to synthetic ACTH. The injections were used as a first line in 8 cases with response in 6(75%). The response to oral steroids was seen in 4/14(29%) cases. A relapse was seen in 2/42(5%) of patients treated with VGB and in 5/25(20%) of those who were treated with synthetic ACTH. The response was highest in the idiopathic group with 7/7(100%). Epilepsy at 2 years was seen in 26/50(52%) and 50/57(88%) of the responders and non-responders, respectively (p=0.000). Only 14/156(9%) of cases had a fair neurological outcome. All of them were from the responder groupConclusion:The response to VGB is suboptimal, while the response to synthetic ACTH is encouraging making it a good alternative for natural ACTH as a potential first line therapy in infantile spasms.

Infantile spasms is an age-dependent epileptic syndrome that typically presents during the first 2 years of life and has a peak presentation at 4 to 9 months of age.^1,2 The spasms are brief seizures that come in clusters and are usually associated with developmental arrest or regression. The characteristic electroencephalographic (EEG) pattern is called hypsarrhythmia and has the form of high amplitude multifocal epileptiform discharges and a chaotic high amplitude slow background.³ Overall, the prognosis of infantile spasms is unfavorable, with 60% having epilepsy and 75% having developmental delay after 2 years of follow-up.⁴ Furthermore, this epileptic syndrome has various causes. The International League Against Epilepsy classifies infantile spasms as cryptogenic and symptomatic. Cryptogenic infantile spasms have no identifiable cause with fair development prior to the onset of seizures.⁵ Symptomatic causes of infantile spasms include prenatal causes, such as brain malformations, intrauterine infections, chromosomal anomalies, and single gene causes.⁵ Premature delivery and periventricular leukomalacia are also becoming important causes of infantile spasms with the increased survival of very premature infants.⁶ Postnatal causes, such as hypoxic ischemic encephalopathy and meningitis, are also common and well-identifiable causes.⁵ Hereditary neurometabolic disorders rarely cause infantile spasms and have only been discussed in case reports; however, they accounted for 12.5% of cases in a study done at our institution.⁷ This was a result of the high rate of consanguineous marriages in the Saudi population.^8,9The 2 treatment modalities that showed benefits with this epileptic syndrome include vigabatrin(VGB) and hormonal therapy.^10-12 The medication that showed the best response rate was ACTH. The response rate varies across studies and is about 50–90%.¹³ The ACTH was also associated with a better outcome and neurocognitive development.¹⁴ High dose oral corticosteroid has been advocated as an alternative therapy with a comparable efficacy of 67%.¹² However, other antiepileptic drugs that showed some efficacy include valproic acid, topiramate, zonesamide, and nitrazepam.¹³ Early treatments may contribute to better outcomes.^15,16The primary goal of this study is to report the efficacy of intravenous (IV) synthetic ACTH (Tetracosactide) in the treatment of infantile spasm patients presenting to a tertiary care center in Saudi Arabia. The secondary goal is to report the response to other modalities particularly VGB and oral steroids, as well as reporting outcomes according to responses.     

Prevalence of depression and anxiety among adult patients with multiple sclerosis at Riyadh City,Saudi Arabia

Objectives:To determine the prevalence of depression and anxiety in adult multiple sclerosis patients attending tertiary facilities in Riyadh, Saudi Arabia.Methods:This is a cross-sectional study conducted among MS patients in Riyadh City, Saudi Arabia. A self-administered questionnaire was distributed among MS patients at Prince Sultan Military Medical City in Riyadh, Saudi Arabia between April 2020 and January 2021. The questionnaire consisted of socio-demographic characteristics and the Hospital Anxiety and Depression Scale (HADS). Univariate using Chi-square test and multivariate regression analysis had been performed to determine the factors associated with anxiety and depression among MS patients.Results:A total of 328 MS patients took part in the study. The most prevalent age group was 36–45 years old (38.4%), with over 70% of the participants being females. Anxiety and depression were shown to be prevalent in MS patients at 42.9 percent and 58.8 percent, respectively. According to statistical tests, being less educated and having partial to severe disability was linked to an increased rate of anxiety and depression, whereas being female was more prone to anxiety symptoms but not depression.Conclusion:Depression was more frequent than anxiety. As a result, while assessing psychiatric diseases in the study group, depression/anxiety may be expected to be more frequent amongst those of greater disability.

Multiple sclerosis (MS) is a central nervous system demyelinating disease caused by an immunological response. Depression and anxiety are more common in patients with multiple sclerosis (PWMS) than in the general population, ^1-4 which is a well-known phenomenon. However, we believe that these illnesses are under-recognized in PWMS because several MS symptoms overlap with depression and anxiety, making detection more difficult. Fatigue, sleeplessness, anorexia, memory loss, and concentration problems are all common symptoms of depression, MS, or both. ^5,6 Furthermore, the symptoms of MS might mislead self-report rating scales designed to detect depression and anxiety, resulting in false positives or negatives. ^5,6 Moreover, depression in PWMS can impair their quality of life (QOL), medication adherence, and compliance, worsening their prognosis. ^7-9 Suicidal thoughts and attempts are also common. ^10-13 The hospital Anxiety and Depression Scale is a one-of-a-kind measure for detecting anxiety and depression while taking into account both disorders’ possible confounders, and it has been validated for use in PWMS. ⁶ Depression is a significant mood illness that affects many people. It creates severe symptoms that impact how you feel, think, and handle day-to-day tasks like working, sleeping, and eating. ¹⁴ In PWMS, the lifetime prevalence of depression in up to 50%, ³ compared to 10.8% in the general population. ¹⁵ The cause of depressive disorders in people with MS is unknown. However, it is assumed to be complex, with psychological, social, and neurological aspects - as well as immunologic and genetic factors - all having a part. ¹⁶ Furthermore, depression can have a severe impact on these patients’ health by raising the severity of their symptoms and reducing their compliance with therapy and follow-up, both of which have an impact on their medical costs. ⁹ In addition to a decreased quality of life (QOL), cognitive impairment, and an increased risk of suicide, especially when anxiety is present. ^7,10,11 Furthermore, PWMS have a 10-year lower life expectancy than the general population of the same age. ² Patients, caregivers, and care providers should not underestimate the impact of sadness and anxiety on PWMS. Improved identification, diagnosis, and treatment in medical offices, where people with mood disorders are frequently seen for the first time, can assist to improve these negative outcomes. ¹⁷ Unfortunately, despite convincing evidence of its high incidence, greater influence on prognosis, and quality of life, depression and anxiety are still underdiagnosed and undertreated. ¹³ The goal of this study is to find out how common depression and anxiety are among adult patients with multiple sclerosis in Riyadh, Saudi Arabia. We’ll also see if there’s a link between Hospital Anxiety and Depression Scale (HADS) score and patients’ demographical, socio-educational, and MS-related characteristics, as well as MS duration, Immunomodulatory type, and EDSS scores.     

Polarity-dependent cerebellar transcranial direct current stimulation modulates online functions of the alerting attention network

Objectives:To investigate the modulatory effect of anodal, cathodal and sham cerebellar transcranial direct current stimulation (ctDCS) on the efficiency of the 3 attention networks namely alerting network, orienting network, and the network of executive control.Methods:A sham-controlled, single-blind study. Experiments were performed at the neuroscience lab of Imam Abdulrahman Bin Faisal University, Dammam, Kingdom of Saudi Arabia, between the months of January-July of 2018. Sixty-three healthy subjects were assessed for eligibility and a total of 60 subjects (30 males and 30 females) met the inclusion criteria. Subjects were randomly divided into 3 groups that received a single 20-minute session of 2 mA of anodal, cathodal or sham ctDCS while performing tasks. The tasks corresponded to the 3 attention networks-vigilance task assessed the alerting network, Posner’s attention task assessed the orienting network and Flanker task assessed the network of executive control. The Edinburgh handedness inventory-short form determined the subjects’ handedness.Results:Analysis of variance (ANOVA) showed a highly significant polarity-independent group*task effect (p=0.003) for the vigilance task. Moreover, there was a significant polarity-independent group*task effect for valid cues (p=0.006). A polarity-dependent group*task effect was observed for invalid cues (p=0.011).Conclusion:Conclusion: Findings demonstrate that ctDCS modulates alerting attention and highlights a more profound effect of cerebellar modulation in attention tasks with higher cognitive load.

In addition to motor theories, the cerebellum is believed to contribute to the execution of non-motor tasks that correspond to cognitive functions.^1-4 With the emergence of neuro-imaging techniques, these theories were supported by showing correlated activation patterns of the cerebral cortex and the contralateral cerebellum in a range of cognitive tasks.^5-7 It was revealed that the cerebral cortex and cerebellum have mirrored network patterns where each part of the cerebrum (motor and cognitive) is represented by an area in the cerebellum.⁸ Several techniques also identified the presence of distinct cognitive closed-loop circuits that do not overlap with motor circuits of the cerebellum.^9,10 Moreover, it was observed that not all patients with cerebellar stroke have motor impairments, highlighting that cerebellar motor syndromes are only associated with lesions in the cerebellar sensorimotor domains of function.¹¹ This suggested that the cerebellum has a unique functional topography for influencing the performance of different cognitive functions.In terms of cognitive functions and specifically attention, Petersen et al,¹² illustrated the presence of 3 distinct but inter-connected networks for attention processing. It was concluded based on a multitude of evidence in the literature, that attention networks are anatomically distinct entities that are not linked to other pathways responsible for input, processing, or output of stimuli. The first network known as the alerting network, is responsible for arousal and vigilance systems where a warning cue activates phasic alteration in a person’s resting state.¹² It represents a tonic alertness where the appearance of a stimulus is followed by a response. The second network or orienting network focuses on filtering the information received to selectively focus on the spatial attributes of a signal, location or sensory stimulus.¹² The third network known as the network of executive control, represents the ability to consciously focus on a target while simultaneously inhibiting interference from stimuli across other sensory systems. It is a state where a target or sensory stimulus is detected amidst the interference of other targets or stimuli.Transcranial direct current stimulation (tDCS) is a non-invasive modulation method where different brain regions are stimulated below the threshold of neuronal damage.^13,14 Low intensity current modulates brain regions, and this leads to the excitation or inhibition of different functions through the process of long-term potentiation (LTP).¹⁵ With the emergence of these techniques, several studies have employed tDCS to investigate the effect of different polarities of current (anode, cathode and sham) on the functioning of the cognitive domain.^16,17 Based on the concept of cerebellar brain inhibition (CBI), it has been proven that the cerebellum imposes an inhibitory effect through the facilitation of Purkinje fibers.¹⁸ This indicates that anodal stimulation facilitates the inhibitory effect of the Purkinje, while cathodal stimulation inhibits that effect and thereby increases excitability.In general, very few studies have investigated the effect of cerebellar modulation on attention networks. Some studies have observed a modulation effect of the dorsolateral prefrontal cortex (DLPFC) on all attention tasks, while others revealed a modulatory effect of tDCS on the network of executive control alone.^17,19 Ferrucci et al,²⁰ also assessed cerebellar modulation using cerebellar transcranial direct current stimulation (ctDCS) and observed improvement in a task that represented the network of executive control. The most recent and relevant study was conducted by Mannarelli et al,²¹ where the attention network test (ANT) was used to assess the effect of ctDCS on the functioning of the 3 attention networks. Findings revealed a significant difference in scores of the network of executive control. In the study paradigm, 7 cue conditions were administered to differentiate between the 3 attention networks. While the functioning of attention networks overlaps in daily life situations, they function separately along the dorsal and ventral visual streams.¹² Moreover, the cerebellum has been proven to have a more profound effect on tasks that impose a higher cognitive load or difficulty.^22,23 Therefore, the paradigm failed to precisely account for distinction between the alerting and orienting networks and overlooked that the orienting network can be sub-divided into several cue conditions that impose a higher mental load or difficulty.Therefore, this study investigated the effect of different polarities of ctDCS on the efficiency of the 3 attention networks. A modified study paradigm was employed to individually assess the 3 attention networks and to investigate the efficiency of functioning of the orienting network based on different cue conditions with varying difficulty. Considering the concept of CBI, anodal current was hypothesized to deteriorate the efficiency of the 3 attention networks. Contrarily, cathodal current was hypothesized to improve the same variables while sham current had no modulatory effect on the 3 attention networks.     

Prevalence of depression among epileptic patients in Taif City,Saudi Arabia

Objectives:To assess depression and its relation with different factors among people with epilepsy in wider range of ages.Methods:A cross-sectional study was conducted in Taif city. The sample size was 150; the inclusion criteria were ≥18-year-old patients diagnosed with epilepsy. The data were collected by interviewing patients following up from rural and urban areas of Taif in neurology clinics at King Faisal Medical Complex (KFMC) and King Abdul-Aziz Specialist Hospital (KAASH). The PHQ-9 score was used to screen for depression.Results:Our study showed that approximately 76.7% (n=115) of the patients had some form of depression. A severe form of depression was identified in 8.7% (n=13) of the patients, and a moderately severe form was observed in 13.3% (n=20) of the patients. There was no significant association between depression and gender, duration of epilepsy, type of epilepsy, and medications for epilepsy, while there was a statistical association between depression and age, stress level, and employment status (p<0.044, p<0.001, p<0.008, respectively).Conclusion:Depression is common in people with epilepsy. Regular screening for depression is recommended in people with epilepsy for early detection and treatment.

Epilepsy is one of the common neurological disorders in the world affecting people of all ages.¹ Approximately 1.5 and 5% of any population will have afebrile seizures at some time.² The prevalence of epilepsy in Saudi Arabia is 6.54 per 1000.¹ There are many psychiatric comorbidities associated with epilepsy.³ Poor adaptation to the new diagnosis of epilepsy has been found to cause different psychiatric disorders.⁴Depression is one of the most common psychiatric comorbidities in people with epilepsy with an estimated prevalence of approximately 10% in the general population and approximately 30% in people with epilepsy.³ Depression in people with epilepsy is associated with a poor quality of life and a high risk for suicidal ideations compared to people with epilepsy without depression.⁵Li et al³ 2019 determined that 29.9% of epileptics had depression, and 15.8% of them had suicidality. Moreover, a case–control study conducted in Greece determined that the Patient Health Questionnaire (PHQ-9) for the evaluation of depression severity was higher in people with epilepsy compared to that in the control.⁵ Fecske et al⁶ indicated that the prevalence of depression in pediatrics with epilepsy was 15%.In 2016, a study was performed in Taif, Saudi Arabia, which showed that 89% of 12–18-year-old adolescents with epilepsy had depression.⁷ Therefore, the aim of this study was to estimate the prevalence of depression among people with epilepsy and its association with demographic characteristics, type of convulsions, duration of epilepsy and number of medications used, and the stress level within a broader range of population.     

Cranial capacity measurement for modern Chinese adults based on 3D reconstruction

Objectives:To determine the average modern adult cranial capacity in China, and assess the gender differences and trends in order to establish normal reference values and provide theoretical basis for individualized treatment in clinical practice.Methods:We conducted a cross-sectional study between January 2019 to June 2020. Thin-slice (0.9 mm) CT scans of 309 males and 238 females from China were obtained, and classified into the 18-32, 33-47, 48-62, 63-77 and 78-92 years age groups. Three-dimensional reconstruction was performed using mimics software to obtain the cranial capacity for statistical analysis.Results:The average cranial capacity of men was 1497.12±120.70 cm3 and that of women was 1326.24±95.72 cm3. The average cranial capacity of men was larger than that of women in all age groups. In addition, cranial capacity across the different age groups showed significant differences among both men and women.Conclusion:The average cranial capacity of modern Chinese male is larger that of females, and both sexes show a tendency to an increase in the intracranial volume over the past few decades. Our findings provide important data for establishing normal reference values for cranial capacity of modern Chinese adults and theoretical basis for individualized treatment of certain cranial diseases with increased intracranial pressure.

Cranial capacity, also known as total intracranial volume (TIV), includes the volume of the brain, cerebrospinal fluid and other structures within the cranial cavity.¹ Studies have shown cranial capacities varies according to geographical regions, race, gender and age.^2,3 While several reports have been published on the cranial capacities of different ethnic and racial groups such as South Africa, India, Korea and America, little is known regarding the cranial capacity of modern Chinese adults.^4,5Cranial capacity is a reliable parameter in pediatrics, forensic medicine, oral surgery and in the diagnosis of cranial cavity deformities.^6,7 However, its application in cerebral hemorrhage and other diseases leading to intracranial hypertension has not been reported in the literature. Everyone have different Cranial capacity, even if the volume of intracranial hematoma is the same, intracranial hypertension will be different. Therefore, when the intracranial hematoma volume is used as an indication of cerebral hemorrhage surgery, the difference of individual cranial capacities should be considered at the same time. It is common knowledge that prior cranial capacity data is usually calculated through filling up the cranial cavity with sand, rapeseed or on the basis of the cranial diameters that are measured through CT images or head.^8,9 However, filling up the cranial cavity with sand, rapeseed and other fillers after autopsy is not an accurate method for obtaining the sample size, and also causes larger error due to the age of the samples. Furthermore, mathematical calculation of the cranial capacity on the basis of diameter also results in large errors, and the meridians and formulae for evaluating the cranial volume are not unified.^9,10 Therefore, there is at present no reliable reference for comparing cranial capacity between different populations. Three-dimensional reconstruction of cranial images and pixel filling is a novel approach for measuring cranial capacity.^11,12 The range of cranial capacity is drawn by the software, which then generates a volume map of the region of interest and measures the volume. It is not only accurate in measurement, but also beneficial to the measurement of cranial capacities with large living samples.¹³Although the cranial capacity is of great significance, there is few report on the measurement of cranial capacity of modern Chinese adults in vivo with large samples of three-dimensional reconstruction technology. Therefore, this study can know the normal reference, sexual dimorphism, individual difference and changing trend of cranial capacity of Chinese modern adults which will provide a theoretical basis for individualized treatment of certain cranial diseases with increased intracranial pressure.     

COMTVal158Met polymorphism is associated with ecstasy (MDMA)-induced psychotic symptoms in the Turkish population

Objectives:To investigate catechol-O-methyltransferase (COMT) Val158Met gene polymorphism in MDMA use disorder (MUD) by comparing genotype distributions between MUD patients and healthy controls considering clinical parameters.Methods:Eighty-two MUD patients’ were consecutively admitted to the outpatient psychiatry clinic in May 2019-January 2020, and 95 healthy volunteers were included in the case-control study. We used the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) to determine COMT Val158Met polymorphism.Results:The COMT Val158Met genotype distribution and allele frequencies of the MUD patient group were significantly different from the healthy control group. The Met/Met genotype (OR: 2.692; 95% Cl: 1.272-5.698; p=0.008) and Met allele frequencies (OR: 1.716; 95% Cl: 1.118-2.633; p=0.013) were significantly higher in the control group than in MUD patients. When the COMT Val158Met genotype and allele frequency distributions were compared between 2 groups according to the psychotic symptoms in the MUD patient group, the COMT Val158Met genotype distributions were significantly different between the groups of patients. The percentage of patients with the Val/Val genotype was significantly lower in MUD patients with a psychotic symptom than the MUD patients without a psychotic symptom (OR: 2.625; 95% Cl: 1.069–6.446; p=0.033).Conclusion:The COMT Val158Met gene polymorphism was found to be related to the MUD-diagnosed Turkish patients and MDMA-induced psychotic symptoms.

3,4-methylenedioxymethamphetamine (MDMA), a ring-substituted amphetamine derivative, is a popular recreational drug best known as ‘ecstasy.’ This group of chemicals, which includes 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxyethylamphetamine (MDE), are named phenylethylamines and characterized by a mixture of hallucinogenic and psychostimulant effects.¹ The MDMA binds to all presynaptic monoamine transporters, most strongly to the serotonin transporter, and causes serotonin and dopamine’s rapid and potent release from presynaptic terminals.² Therefore, MDMA-related psychopathologies may be related to excitotoxicity, mitochondrial dysfunction, or oxidative stress in serotonergic and dopaminergic systems.³ Short-term neuropsychiatric consequences of MDMA can be counted as increased self-acceptance, self-confidence, reduced inhibitions, and heightened sexual sensitivity.⁴ The long-term neuropsychological outcomes of MDMA were investigated in several types of research but have shown different results. The most common findings were anxiety, depression, psychotic symptoms, memory, and attention deficits.⁵Catechol-O-methyltransferase (COMT) enzyme has a role in the degradation of dopamine and different catecholamines, and the COMT gene is expressed from chromosome 22q11.2. Decreased COMT enzyme activity is related to valine’s amino acid change to methionine caused by a guanine-to-adenine substitution at codon 158 of the COMT gene.⁶ In the brain, the COMT Val158Met (rs4680) polymorphism has been determined to change the activity of COMT, which probably causes alteration in dopamine neurotransmission and may end with behavioral abnormalities since dopamine takes a unique position in addiction.⁷ Besides, there are studies of Val158Met for psychiatric disorders such as bipolar disorder (BD), schizophrenia (SCZ), and substance use disorder (SUD) that have shown contradictory results.^8-10 Many researchers showed statistically significant relationships of the COMT Val158Met polymorphism in subphenotypes of psychiatric disorders such as SCZ patients with homicidal or aggressive behavior or BD with rapid cycling.^11,12 Again, although some reports indicate a positive association between COMT polymorphisms and addiction, most studies have not detected a link between them.^13-15 The lack of evidence in a relationship suggests additional studies about the association of the COMT gene with SUD.Therefore, we hypothesized that the COMT Val158Met polymorphism might be related to the MUD and some clinical parameters such as the comorbidity of the alcohol or cigarette use disorder, the presence of attempted suicide, and psychotic symptoms. We aimed to investigate the association between the MUD and COMT Val158Met gene polymorphism by comparing healthy controls and considering clinical parameters.     

Public knowledge and awareness of stroke among adult population in Taif city,Saudi Arabia

Objectives:To evaluate the knowledge and awareness of stroke in adult population in Taif, Kingdom of Saudi Arabia and to address the association between several sociodemographic variables of participants and their knowledge regarding stroke.Methods:A cross-sectional study was conducted among adult residents in Taif, Kingdom of Saudi Arabia, during the period of December, 2020 to February, 2021 using an online questionnaire.Results:Our study included 3456 participants (43.6% males, 56.4% females). Analysis showed that 61.7% of the participants were aware of stroke. Participants who were 15-39 years-old had good knowledge. Male participants had better knowledge than females. The most identified risk factor was ‘unhealthy lifestyle’ (84.5%) and the least identified one was ‘epilepsy’ (34.8%). The most identified symptom was ‘slurred speech’ (57.5%), and the least identified one was ‘dizziness’ (36.2%). Approximately 86.6% of the participants agreed that stroke was a medical emergency. A total of 41.5% of the participants agreed that stroke was treatable and 42.6% agreed that stroke was a preventable disease.Conclusion:Although the participants recognize that stroke is a medical emergency and that early intervention is crucial, the obtained results show that there is a large gap in the knowledge of the warning signs and symptoms of stroke. Increasing community awareness about these warnings may affect how quickly the patient is treated.

Stroke is a serious neurological disorder, and it is one of the major causes of long-term disability.¹ Global prevalence of stroke is estimated to be 80 million cases in 2016.² Stroke can occur owing to ischemia or hemorrhage and causes damage of brain tissue leading to neurological function and cognitive deficits.³ Among different types of stroke, blockage of arterial supply in the brain, which is known as ischemic stroke, is the most common type of stroke.⁴ Stroke is a preventable neurological disease that has many modifiable risk factors. Patients with chronic diseases (namely, hypertension, diabetes mellitus, hyperlipidemia, and cardiac disease) or cigarette smokers (which are the commonest risk factors) are considered to have higher risk of stroke.⁵ Stroke risk increases in women using an oral contraceptive pills for long duration.⁶ Lifestyle modification (namely, salt restriction, smoking cessation, sports, and maintaining normal weight) can reduce the risk of stroke up to 50%.⁷ The incidence of stroke is decreasing in many countries due to improved high blood pressure control and decreased levels of smoking.⁸ Patients with risk factors should be aware of the risk of stroke and must have knowledge about the warning signs. Stroke warning signs include sudden numbness or weakness of the face or limbs, confusion, speaking difficulties, difficulty seeing, difficulty walking, and severe headache with an unknown cause.⁹ Early identification of stroke symptoms with early management of acute attack is very effective to reduce the burden of stroke complications.¹⁰ Lack of knowledge of the warning signs and the importance of time to manage stroke attack may lead to delay the decision of seeking medical help.¹¹ Increasing stroke awareness expedites stroke symptom recognition and seeking medical attention.¹²Stroke is the second leading cause of death worldwide (9.7% of all deaths) just after ischemic heart disease.¹³ With aging, the incidence of stroke increases. The incidence reaches 670-970 of 100,000 per year for people over 65 years old.¹⁴ The incidence of stroke in Kingdom of Saudi Arabia (KSA) is 29 per 100,000 people annually.¹⁵ It is a major cause of death and disability in KSA (with up to 6.4% mortality rate).¹⁶     

Clinical delineation of myasthenia gravis in the Kingdom of Bahrain

Objectives:To report demographic and clinical data on 98 myasthenia gravis (MG) patients, seen over 5 years (January 2014-December 2018).Methods:This was a retrospective, observational cohort study carried out at 3 hospitals in Bahrain. MG was classified into ocular or generalized types. We subdivided MG into early-onset (EOMG, ≤ 49 years) or late-onset (LOMG, > 49 years). Demographic and clinical data were recorded. The data was entered and analyzed using SPSS version 26.0.Results:61.2% were females. The mean age at onset was 43.8±17.7 years in males and 43.1±15.7 years in females. 72.4% had EOMG. A pure ocular presentation was most common (51%). Limb weakness was more prevalent in AChR-positive patients. The MuSK group had more severe presentation. 57.1% of patients were AChR-positive, 3.1% MuSK-positive, and 39.8% double-seronegative. Generalized disease onset was more likely with AChR. Abnormal CT chest was seen in 24/69 (35%) including thymic hyperplasia, thymoma, and thymic atrophy. Pathology findings were thymic hyperplasia (55.0%), thymoma (30%), thymolipoma (10%), and normal thymus (5%). Treatment outcomes were favorable.Conclusion:The present study revealed that MG was more common in females, with similar age at onset between males and females. The majority of patients had EOMG with ocular disease and AChR positivity. The clinical outcomes were favorable. Following a standardized protocol for MG diagnosis and workup is recommended.

Myasthenia gravis (MG) is an autoimmune disease of neuromuscular transmission, characterized by fatigable muscle weakness,¹ mediated by an antibody attack on components of the postsynaptic membrane of the neuromuscular junction, such as the acetylcholine receptor (AChR), muscle-specific tyrosine kinase (MuSK) and lipoprotein receptor-related protein 4 (LRP4).^2,3 This may result in various distribution of muscle weakness among different patients, including ocular and limb weakness, bulbar involvement, and sometimes respiratory failure, as well as various degrees of severity.^2,4,5 The MG is the major disorder that affects the neuromuscular junction, while other rarer syndromes include the Lambert-Eaton myasthenic syndrome and botulism, both affecting the presynaptic neuromuscular junction.⁴ The Myasthenia Gravis Foundation of America (MGFA) clinical classification (class I ocular, class II mild generalized weakness, class III moderate generalized weakness, class IV severe weakness, and class V needing intubation) is used to identify subgroups of MG patients sharing certain clinical features or disease severity, which may help predict disease prognosis and treatment outcome.⁶Based on serum antibody profile and clinical phenotypes, MG can be classified into seven subgroups: early-onset MG (EOMG), late-onset MG (LOMG), thymoma-associated MG, MuSK MG, LRP4 MG, ocular MG, and seronegative (SN) generalized MG.^4,5,7 This classification is clinically useful, as there are important differences in terms of clinical features, thymus abnormalities, treatment outcome, and drug adverse events among different phenotypes.^2,5 For example, Deymeer et al⁵ compared the clinical characteristics of 32 anti-MuSK MG, 161 anti-AChR MG and 33 SN MG patients. The MuSK MG group had more bulbar involvement and more severe disease with crises, while the SN group had a milder disease with a good outcome and lower percentage of steroid maintenance doses and use of other immunosuppressants such as azathioprine. Females predominated in all 3 groups.In general, the prognosis of MG is good, due to early diagnosis and availability of symptomatic treatment, and the use of effective immunosuppressants and other supportive measures.⁴ The aim of our study was to retrospectively gather data on the clinical characteristics of MG patients in the Kingdom of Bahrain, and compare it with regional and international data.     

Sjogren’s syndrome associated with bilateral peripheral facial paralysis

Sjogren’s Syndrome (SS) is a chronic autoimmune disorder that may be complicated by neurological dysfunctions. The involvement of cranial nerves in SS was described as a very rare complication. Moreover, bilateral peripheral facial paralysis associated with SS has been described only in 3 patients in the literature and the first case was described by Henrik Sjogren himself in 1935. We report a 59-year-old female with bilateral peripheral facial paralysis associated with Sjogren’s syndrome. She was treated with 5-day IVIG consecutively and continued oral methylprednisolone 16mg/day and almost fully recovered at 2 months of follow-up examination. Acute bilateral peripheral facial palsy in SS is a very rare condition and Lyme disease, Guillain-Barré syndrome, HIV infection, and central nervous system lymphoma should be considered in the differential diagnosis. As a result, SS should be considered as an underlying cause of bilateral facial paralysis.

Sjögren’s Syndrome (SS) is a systemic chronic autoimmune and vasculitic disorder characterized by lymphocytic infiltration of lacrimal and salivary glands.¹ In 39% of the affected cases, the disease can start with neurological findings. The most common peripheral involvement of SS is sensory neuropathies.²Peripheral facial paralysis associated with primary SS has been described in very few cases, and most of them were unilaterally affected.³ Only three had bilateral facial nerve involvement.⁴ Here, we described a patient with SS, who presented with bilateral facial nerve involvement.     

Public awareness of the neurological manifestation of COVID-19 in Saudi Arabia

Objectives:To assess awareness of the neurological manifestation of COVID-19 on the Saudi population.Methods:This was a cross-sectional study conducted using a Google Form survey to obtain responses randomly from the Saudi population between February and March 2021 using social media.Results:A total of 831 participants completed the questionnaire. The distribution of the identified isolated neurological manifestations of COVOD-19 infections by participants’ age was assessed among the respondents. Loss of smell (88.9%), loss of taste (86.8%), and headache (72.6%) were the most identified first manifestations among all the age groups, while stroke (13.4%) was the least identified for all ages with no statistical significance (p>0.05 for all). Regarding COVID-19 related neurological symptoms, the same was reported: loss of smell, taste, and headache were the most identified symptoms among all the age groups, while stroke was the least identified for all ages with no statistical significance (p>0.05 for all).Conclusion:The study concluded that awareness of COVID-19’s neurological symptoms could help detect an atypical case, which can help in early intervention and its medical treatment. Moreover, the study also suggested conducting educational programs that emphasize the early identification of neurological symptoms of COVID-19.

COVID-19’s first case was identified in 2019 in Wuhan city of China, and then in the year 2020, this spread globally, causing a pandemic.^1,2 It is found that the COVID-19 virus does not find its way into the respiratory system as other respiratory viruses do. This virus is transmitted through various means such as via droplets, airborne, and even through surfaces, and at any time; therefore, it is very difficult to control the virus from spreading.^2,3 This virus can affect various bodily functions, causing multiple symptoms, and eventually lead to acute organ damage or even endless sequels. Although the most common manifestation is fever and respiratory tract symptoms, extrapulmonary symptoms include hematological problems, cardiac arrest, acute kidney injury, gastrointestinal pain, liver damage, neurological illnesses, ocular manifestation, and dermatologic complications.^2,4,5 Several studies have shown that patients of COVID-19 could show signs of the central or peripheral nervous system that can vary from mild to severe (loss of taste and smell, headache, dizziness, ischemic stroke, delirium, and encephalitis). These symptoms can appear before the start of fever, respiratory tract, or as an isolated manifestation.^6-9 Therefore, this study has evaluated public awareness about the neurological appearances of COVID-19 among the Saudi population.