The role of ketogenic diet in controlling epileptic seizures

Objectives:To study the role of the ketogenic diet (KD) in controlling seizures in children with medically resistant epilepsy in Saudi Arabia.Methods:This retrospective study was conducted in the Pediatric Neurology Clinic at a tertiary care epilepsy center. Thirty-one patients with medically resistant epilepsy were enrolled from 2013 to 2018. The seizure reduction variables were evaluated at 6, 12, 18 and 24 months after enrollment.Results:Of the 31 patients, 14 (45.2%) were males and 17 (54.8%) were females. The most common types of seizures were myoclonic seizures and mixed seizures, both of which occurred in 9 (29%) of the participants. Of the participants, 15 (48.4%) had seizures one to 5 times per day. Six months after starting a KD, 2 (6.45%) of participants were seizure-free; 6 (19.35%) were seizure-free after 12 months of treatment.Conclusion:The present study highlighted the effectiveness of KD in medically resistant epilepsy children to local population. A larger cohort is warrant to confirm these findings.

Epilepsy is a common neurological disorder. It is characterized by seizures and affects approximately 65–70 million people worldwide.1 Children and the elderly are most commonly affected by seizures; the condition is rarer in adults.2 Epilepsy remains a challenging neurological disorder despite effective pharmacological therapies.3 More than 30% of epileptic patients do not achieve complete control of seizures with available anti-epileptic drugs (AEDs).1,4 Around 20-40% of patients with epilepsy have refractory epilepsy “failure of, adequate trials of 2 tolerated, appropriately chosen and used AED schedules (whether as monotherapies or in combination) to achieve the sustained seizure freedom” and who are not candidates for surgery, non-pharmacological interventions should be considered for ketogenic diet (KD) treatment.5,6The KD has been proposed for first time in 1920s as a non-pharmacologic treatment to control refractory childhood epilepsy.1 The KD is a high-fat, low-protein, low-carbohydrate diet, with ketogenic ratio of 4:1 or 3:1 in grams which is the most commonly administered ratio.7,8 The KD increases the production of ketone bodies, which brain uses these ketone bodies as an energy source instead of glucose.2 Some hypotheses have been proposed regarding the KD’s anti-seizure effects, suggesting that changes in the nature and degree of energy metabolism in the brain, changes in neurotransmitter function, changes in synaptic transmission, and changes in neuronal cellular properties may explain the diet’s effectiveness.9 Higher ketone levels correlate with better seizure control.9 Ten to 15% of children with epilepsy become completely seizure free on a KD.3 Furthermore, the KD has a prolonged beneficial effect even after it is discontinued.9The International Ketogenic Diet Study Group strongly recommends that the KD be considered as a treatment for children with epilepsy who fail to respond to two or three anticonvulsant medications, regardless of age or gender.9 Our objective was to study the efficacy of the KD in children with medically resistant epilepsy in Saudi Arabia.     

The comorbidity of headaches in pediatric epilepsy patients: How common and what types?

Objectives:To estimate the prevalence and characteristics of headache in pediatric epileptic patients.Methods:This cross-sectional study was performed over 6 months period from January 2018 to June 2018 at King Abdullah Specialist Children Hospital, King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia using a structured questionnaire in pediatric patients with epilepsy.Results:There were 142 patients enrolled (males, 57.7%; average age, 10.7±3.1 years) with idiopathic epilepsy (n=115, 81%) or symptomatic epilepsy (n=27, 19%). Additionally, patients had focal epilepsy (n=102, 72%) or generalized epilepsy (n=40, 28%), and among them, 11 had absence epilepsy. Overall, 65 (45.7%) patients had headaches compared with 3/153 (2%) in the control group (p < 0.0001). Among the 65 patients with headaches, 29 (44.6%) had migraine-type, 12 (18.4%) had tension-type, and 24 (36.9%) had unclassified headache. There was no significant difference in age, gender, type of epilepsy syndrome, and antiepileptic used except in patients with or without headache. For migraine patients, there was a lower headache prevalence in the subgroup treated with valproic acid compared with other treatments.Conclusion:Headache, predominantly migraine, is a common problem in pediatric epileptic patients and choosing valproic acid when possible can be important in preventing migraine in these patients.

Epilepsy and headache are chronic paroxysmal disorders that affect adult and pediatric patients1 with episodic manifestations. Headache or (cephalalgia) is defined as a feeling of pain in the region of the head or neck. Primary headaches include migraines, tension-type headache, and cluster headache. Epileptic seizure is a brief episode of signs or symptoms caused by abnormal excessive synchronized neuronal activity.2 Epilepsy is defined as a condition where the patient has an enduring tendency to have recurrent unprovoked seizures.2 These two disorders coexist in some patients.3 There are few studies on the comorbidity of headaches in children with epilepsy.4-6 Other studies reported a significant association between migraine and epilepsy.1,7-9 Additionally, the genetic predisposition for both entities was reported in some forms of channelopathy,10 and others found more prevalence of migraine headache in specific diseases in pediatric like benign epilepsy with centrotemporal spikes and juvenile myoclonic epilepsy.11 Seizure-associated headache is common, with an incidence of 42–51% in adult epileptic patients.12 However, for pediatric patients, it is often neglected by parents and physicians because of other neurological manifestations of the seizure such as loss of consciousness and motor components,13 and approximately 36% of the parents were reported to be unaware that their children experienced headache.14 It is our experience that headache is a common problem in up to 50% of epilepsy patients but we do not know exactly the prevalence, in addition to what type of headache is most commonly found in epileptic pediatric patients. Because of few reports on this topic have conflicting results, the objective of this study was to evaluate the prevalence and characteristics of headache in children with epilepsy who were seen at one center in Saudi Arabia.     

Knowledge of and attitudes toward epilepsy surgery among neurologists in Saudi Arabia

Objectives:To investigate the levels of knowledge and attitudes toward epilepsy surgery among neurologists in Saudi Arabia and evaluate the factors that affect the physicians’ knowledge and attitudes.Methods:A quantitative observational cross-sectional study conducted at King Saud University Medical City, Riyadh. The data were collected using a newly developed, self-administered online questionnaire. The questionnaire contained 3 sections: demographic information, knowledge, and attitudes which then sent to neurologist in Saudi Arabia from December 2016 to March 2017.Results:A total of 106 neurologists met our inclusion criteria. Eighty percent of the participants had at least one epilepsy center in their city, and 78% indicated that they had access to adequate expertise and resources to enable the appropriate selection of epilepsy surgical candidates. Only 57.5% of the neurologists had a sufficient level of knowledge regarding epilepsy surgery. Neurologists with higher level of knowledge referred more patients to EMU and discussed epilepsy surgery more often with their patients. Overall, more than half of the neurologists (52.8%) had a positive attitude toward epilepsy surgery. There was a significantly positive correlation between the scores of knowledge and attitude (p<0.001).Conclusion:Neurologists in Saudi Arabia appear to have moderate knowledge of and positive attitudes toward epilepsy surgery. The place of the last neurology certificate, type of practicing hospital, and access to expertise and resources, affected their knowledge. Adequate knowledge was positively correlated with attitude.

Epilepsy is one of the most common neurological disorders in Saudi Arabia, with an estimated prevalence of 6.54 per 1000 individuals.1 It is estimated that 20-40% of newly diagnosed patients are expected to fail seizure control with medical treatment.2 Refractory epilepsy is commonly defined as the failure to achieve freedom from seizures despite two or more antiepileptic drugs (AEDs).3 Patients with drug-resistant epilepsy (DRE) have a lower quality of life and face more social difficulties than patients with controlled epilepsy.4-6 More than half of the economic burden of epilepsy is accounted for by patients with refractory epilepsy.7 Epilepsy surgery is the best evidence-based treatment option for these patients with drug resistant focal epilepsy.8,9 The current guidelines for patient referral to epilepsy surgery were published in 2003 by the American Academy of Neurology.9 The benefits of epilepsy surgery may not only reduce the frequency of seizures but might also lower mortality and improve the quality of life.10 Despite its proven efficacy and favorable outcome, the average referral delay of an epilepsy surgery candidate is more than 20 years.11 This delay is predominately attributed to non-adherence to referral guidelines, which results from a lack of awareness and familiarity with them.12 Another factor that contributes to the delay is patients’ misbeliefs regarding the surgery’s risks and benefits, which are highly influenced by physicians’ lack of knowledge.13 Epilepsy surgery was introduced to Saudi Arabia in 1998.14 Several epilepsy surgery centers have subsequently been established across the country. A survey in 2013 showed that 56% of health-care professionals in Saudi Arabia were not aware that surgery was a treatment option for patients with epilepsy.15 Our aims in this study were to investigate the levels of knowledge and attitudes toward epilepsy surgery among neurologists in Saudi Arabia and evaluate the factors that affect the physicians’ knowledge and attitudes.     

Predicting future handedness and hemispheric dominance during infancy by analyzing sleep spindles

Objectives:To investigate whether sleep spindles asynchrony (SSA) using scalp sleep electroencephalogram (EEG) among children below 2 years of age can predict future handedness.Methods:This is a retrospective study conducted from October 2016 until June 2017 at the King Fahad Medical City (KFMC), Riyadh, Kingdom of Saudi Arabia. We retrospectively reviewed 300 EEGs recorded at our neurophysiology laboratory.We included EEGs performed during sleep for infants aged 2 months to 2 years who have already attained their handedness or those aged above 2 years. We excluded records of children younger than 2 months or above 2 years of age (at the time of the EEG) or those aged below 2 years (at the time of the interview), and severely abnormal tracings and those without sleep or enough SSA .Results:The lateralization of Sleep Spindles (SS) was mostly right-hemispheric (52%) compared to left-hemispheric (36.4%). The overall SS laterality did not correlate with handedness (p=0.81). In the majority of right-handed (64%) and left-handed (60%) children, the SSA was contralateral to the side of hand preference; however, it did not correlate statistically (p=0.377).Conclusion:We were unable to prove a statistically significant correlation between SSA and future hand preference. Further research involving larger cohorts is still needed.

Sleep architecture is an essential part of evaluating any electroencephalogram (EEG). Despite being recognized and described as early as the discovery of EEG, sleep features remain understudied. In most children, Sleep Spindles (SS) do not synchronize over the 2 hemispheres until the child develops Handedness, usually at 2 years of age. This coincidence of the establishment of Handedness and synchrony of SS makes the connection between the 2 maturational developments important. We planned to investigate the possibility of anticipating future hemispheric dominance and future Handedness using the concept of Sleep Spindles Asynchrony (SSA). The SS consist of bilaterally symmetric low to medium voltage bicentral synchronous rhythmic spindle-like waves, with frequency ranging from 12 to 16 Hz, which often appear along K-complexes lasting approximately 2-3 seconds.1 The identification of SS is easy in any sleep EEG due to their abundance in infants and children. Their typical location in adults is a synchronous burst of waves around the vertex; in children, it varies according to age.2–7 It is thought that the origin of sleep spindles is the thalamocortical network. However, there is no functional meaning definitively established for this mechanism so far, which makes our study relevant to this area.3 The SS are not seen in the first 2 months of life and start to appear afterward.8 The absence of sleep spindles during mid-infancy is considered a significant abnormality. However, their independent occurrence (asynchrony) below 2 years of age is common and a normal finding.9–12 These sleep milestones are consistent between subjects, and therefore they are an essential indication of functional maturation.13 Chatburn et al14 found that sleep spindle activity was associated with various aspects of maturation and is an integral part of brain development. It is suggested that sleep EEG may be a marker for intellectual ability.15 Specifically, SS are associated with the intelligence quotient (IQ).16 The SS are also found to be involved in procedural memory.17 There are a few speculations about how Handedness is created in individuals. Although antenatal mechanisms might be essential, analysis considering in utero development verified that Handedness was an extremely accurate indicator of hemispheric dominance after birth.18 Early hand preference does not develop before one-year of age, and the usual age at which Handedness appears is 2 years, coinciding electrographically with SS synchrony, making a causal relationship or mechanism between the 2 markers highly likely.19–20 There is no previously published research to date to have studied this area.21     

Consanguinity in patients with mesial temporal lobe epilepsy due to hippocampal sclerosis in a Saudi population

Objectives:To investigate if there is an association between consanguinity and hippocampal sclerosis (HS) in the Saudi population.Methods:A retrospective case-control study was conducted by assessing the prevalence of consanguinity in patients with pathologically proven HS, who underwent epilepsy surgery at King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia, between January 2004 and December 2015. We reviewed the medical records to extract data, which included; age, gender, duration of epilepsy, history of febrile seizure, family history of epilepsy in a first or second-degree relative, and pathology reports.Results:A total of 120 patients, out of which 40 patients (65% male) having mesial temporal lobe epilepsy due to HS, and 80 controls (56% male) with cryptogenic epilepsy, were identified. Twenty-two patients (53.5%) in the HS group had a history of consanguinity. In the control group, 30 patients (37.5%) had a history of consanguinity. The odds ratio was 2.04 (95% confidence interval = 0.94 - 4.4, p = 0.052). A family history of epilepsy was found in 28% of the patients with HS and 32.5% cryptogenic epilepsy. Only 8 patients (19.5%) with HS reported a history of febrile seizure.Conclusion:Our retrospective case-control study suggests that consanguinity might increase the likelihood of developing HS.

Consanguineous marriage, in clinical genetics, is defined as a union between couples related as second cousins or closer.1 Saudi Arabian culture has a higher consanguinity rate than other Arab, Asian, and Western communities. Consanguinity is not known to increase the risk of idiopathic or cryptogenic epilepsy, based on recent studies from Saudi Arabia and UAE.2,3 However, there is a strong evidence that the marriage of first cousins is one of the main reasons for the increased prevalence of autosomal recessive diseases.4The association between consanguinity and epilepsy due to hippocampal sclerosis (HS), the most common pathology found in patients with intractable focal epilepsy, has not been adequately studied.5 A familial type of mesial temporal lobe epilepsy (FMTLE) has been described with homogeneous and heterogeneous clinical manifestations.6-8 Moreover, magnetic resonance imaging (MRI) of the brain of asymptomatic first-degree relatives of patients with confirmed FMTLE showed evidence of HS, which supports the genetic predisposition to FMTLE.9 Although, FMTLE is widely recognized as an autosomal dominant disease with incomplete penetrance, autosomal recessive or X-linked forms have also been reported. Still, they have not been confirmed by extensive studies.10In this study, we aimed to investigate the association between consanguinity and HS in a Saudi population. This study may help expand our knowledge of the underlying mechanisms of HS and may shed some light on a possible genetic substrate that contributes to the development of HS in this population.     

Patterns and prognosis of Ventriculoperitoneal shunt malfunction among pediatrics in Saudi Arabia

Objectives:To examine the predictors of pediatric ventriculoperitoneal (VP) shunt malfunction in a university hospital.Methods:A retrospective cohort was conducted. Patients under 18 years old who underwent VP shunt revision at least once between 2016 and 2019 were included. Data were stratified based on age, gender, diagnosis, type of valve, valve position, cause of revision, and part revised.Results:A total of 45 patients (64% males and 36% females) were included in this study. Eighty-two revision surgeries were identified. The most common revised part was the entire shunt system. The most common type of valve which required revision was the low-pressure valve (15.5%). Since a p-value of less than 0.05 was considered significant, no significant differences among the 4 groups for different points.Conclusions:Younger age at initial VP shunt insertion is associated with a higher rate of shunt malfunction. Valve mechanical failures followed by infections are the most common causes for the first 3 revisions. A prospective multi-center study to confirm the current findings is recommended.

Ventriculoperitoneal (VP) shunt insertion is one of the most common procedures in pediatric neurosurgery for treating hydrocephalus.1 Among pediatric age group hydrocephalus is considered a common, surgically correctable condition in which there is an increase in the volume cerebrospinal fluid (CSF), leading to cerebral ventricles dilatation, thinning of the cerebral mantle, and elevation of intracranial pressure.2 Patients with VP shunts represent more than 30,000 hospital admissions per year.2 Although VP shunting has decreased the morbidity and mortality of hydrocephalus, it is still associated with multiple complications, many of which require surgical revision.1–4 Recent studies have reported the rate of complications following VP shunting to be between 30% and 50%.3–6 Shunt malfunctions causes can be categorized into infectious, mechanical, or functional.2–4 Shunt failure definition is revision or replacement of the original shunt between 30-days and 1-year.2 Mechanical failure can happen at the proximal end, valve, or distal end, and it includes obstruction, disconnection, fracture, distal end migration, or inflammation. Functional failure happens when there is overdrainage or underdrainage of cerebrospinal fluid while the whole shunt system is properly functioning. Infection happens when the patients demonstrate clinical findings and positive fluid sampling results.3 The most common complication necessitating revision are obstruction, infection, and displacement.2,3,6,7 Shunt failure is most common within the first 2 years postoperatively.3 Many important predictors of VP shunt failure have been reported in the literature, including etiologies of the hydrocephalus, prematurity, and age at the initial placement of the shunt.1,8,9 Clinical factors that may increase the risk of shunt revision include time from the first surgery, surgical procedure duration, prior treatments, number of surgeons, surgical expertise, surgical technique, anatomic site of the shunt, and diagnosis.1,7–10 Proximal catheter tip location is another predictor, as tip positions in the Foramen of Monro, lateral ventricles, or the third ventricle all were associated with lower rates of surgical revision.11 Other predictors of shunt failure were reported to be poor catheter placement and use of a non-programmable valve.12Previous studies have emphasized the need to identify children at risk, and for prospective cohorts to to investigate the relationship of risk factors and incidence of shunt revisions.1,9,10 Risk factors for VP shunt complications vary across institutions and populations, and a very limited number of studies addressing VP shunt malfunction have been conducted in Saudi Arabia, and only one in the last 10 years was published.13The goal of this study was to determine patterns and predictors of pediatric VP shunt malfunction, causes of the hydrocephalus and VP shunt revision and type of valve malfunction and define the best preventive measures. This knowledge will contribute to lowering the incidence of shunt malfunction, decreasing the number of surgeries, and increasing complication-free intervals between surgeries in hydrocephalic pediatric patients.     

Complementary and alternative medicine use among ischemic stroke survivors in Jeddah,Saudi Arabia

Objectives:To determine the prevalence and pattern of complementary and alternative medicine (CAM) use and the CAM types used by stroke patients in Jeddah, Kingdom of Saudi Arabia.Methods:This cross-sectional study included 152 ischemic stroke survivors who visited King Fahad Hospital, Jeddah, Kingdom of Saudi Arabia, between January 2018 and December 2019. Phone-based and face-to-face surveys were conducted. Data on the patients’ demographic characteristics, their use of CAM, and their pattern of CAM use were gatheredResults:Ninety (59.2%) stroke patients used CAM, mainly cauterization (29.61%) and Quran recitation by a religious sheik (28.95%). Most of the patients (72.22%) used CAM post-hospitalization and within less than one month from stroke onset (62.22%). A minority (6.67%) of the patients stopped their medication while on CAM. Some patients (25.56% to 31.11%) discussed with their physician their use of CAM. The CAM users reported a subjective improvement in their physical weakness (45.6%) and psychological wellbeing (62.2%). The patients learned about CAM mainly from their relatives and friends (96.7%), and the most common reason for their CAM use was their belief in this intervention (42.22%).Conclusion:The CAM use was prevalent among our cohort of Saudi ischemic stroke patients, and cauterization and Quran recitation were the most commonly used CAM interventions. An effective communication was lacking between the medical professionals and the stroke patients as regards CAM use despite the interest of the patients in this intervention.

Over the past 2 decades, the burden of stroke has increased globally.1 Stroke is the second leading cause of morbidity and mortality; the annual incidence of stroke is approximately 15 million, and over 5.5 million stroke-related deaths occur annually.2–4 Also, the prevalence of the modifiable risk factors of stroke is increasing, and the burden of stroke increases with the aging of the population.5 Adults aged >25 years have an estimated lifetime stroke risk of 24.9%.6 Despite the advancements in acute stroke care, highly effective treatments for the later phases of stroke are lacking. This shortcoming in the stroke care leads patients and their relatives to seek other treatment options, such as complementary and alternative medicine (CAM).7 The CAM is defined by the United State of America National Institutes of Health as “a group of diverse medical and health care systems, practices, and products that are not generally considered conventional medicine.”8 The CAM has been used for a long time now,9 and people widely practice CAM for various health conditions, such as cancer, epilepsy, multiple sclerosis, infertility, surgical procedure, dermatological conditions, hypertension, pain, and other types of illnesses.1,9–11 The prevalence of CAM use varies by country. For example, the prevalence of CAM use is 82% in the United States,12 61% in Australia,13 51% in Malaysia,14 and 61% in Turkey.15 Religion, cultures, and values influence the types and patterns of its use.16 People in Western countries practice herbal medicine, reflexology, aromatherapy, massage, osteopathy, meditation, and spiritual healing;10,17–19 by contrast, those in Asian countries such as China, India, and Taiwan commonly use therapies such as traditional Chinese medicine, Ayurvedic medicine, physical exercises, acupuncture, Tai Chi, yoga, and homeopathy.20–23 In Saudi Arabia, different types of CAM are used including the Quran recitation therapy, honey consumption, plant-based traditional medicine (e.g., Murrah and black seed consumption), cupping (“Hojamah”), and cauterization (“skin ironing”)9,24–27Research highlighted that aside from their potential benefits, some types of CAM have many side effects and potential toxicities, and patients are commonly unaware of these possible dangers.28 One study reported 2 cases wherein the cauterization led to severe complications, such as skin burn.29 Another study that investigated the components of herbal medicines in Saudi Arabia indicated that 15.7% of the tested samples contain toxic amounts of heavy metals, including arsenic and mercury.30 Despite the potential risk of many CAM interventions, it has been noted that many patients do not inform their physicians about their practice of CAM.31Stroke patients in many countries, including the United States (30.6%–46%)32,33 and South Korea (54%), use CAM.34 In Riyadh, Saudi Arabia, 67% of patients with neurological problems use CAM,9 and most of them use cupping (Hojamah) (45.4%), herbal medicine (42.3%), cauterization (33.7%), and Quran recitation (20.4%).9 However, no available study has analyzed the use of CAM particularly by stroke patients in Saudi Arabia. Thus, this study aimed to determine the prevalence and pattern of CAM use and the types of CAM being practiced by ischemic stroke patients relation to their demographic data.     

The etiology and risk factors of convulsive status epilepticus in pediatric patients of tertiary center in Saudi Arabia

Objectives:To assess the etiology of status epilepticus (SE) among the pediatric patients of a tertiary center in Jeddah, Kingdom of Saudi Arabia (KSA).Methods:Data from 88 cases was obtained retrospectively from 2006 to 2017 from King Abdulaziz University Hospital (KAUH). Patients aged between 28 days and 14 years with the symptoms of SE were selected for this study.Results:The data show that the proportions of SE etiologies were 30.5% for febrile seizure, 11.9% for electrolytes imbalance, 8.5% for hydrocephalus, 6.8% for CNS infections, and 6.8% for neoplasm. The other etiologies of SE were trauma, fever, intractable epilepsy, cerebrovascular accident, hemorrhagic stroke, etc. There were no clear etiologies in 8 cases. Most of the patients were not of Saudi origin (64.3%), boys (67.8%), and had generalized epilepsy types (91.8%), and 58.6% of the patients complied with epilepsy medications.Conclusion:The most prevalent etiology of convulsive status epilepticus was a febrile seizure, followed by electrolyte imbalance and hydrocephalus. However, a nationwide study in KSA must be conducted to determine the major etiologies of SE for its effective management and prevention. Educating families and patients regarding antiepileptic drugs is necessary.

Status epilepticus (SE) is a life-threatening seizure and common pediatric crisis. It is the most critical case of seizure. For every 100,000 children, 73 had SE. The younger the child, the higher the incidence of SE will be. The incidence of SE in children aged less than 2 is high at 156 per 100,000 and is at the highest for infants.1-3 The SE is the commonest pediatric neurological emergency and a major cause of admission to the pediatric intensive care unit (PICU). Historically, many attempts have been made to define and explain seizure and SE. The International League Against Epilepsy (ILAE) recently defined SE as generalized convulsive SE for any tonic-clonic seizures that continue more than 5 minutes, as focal SE for any focal seizure that continues more than 10 minutes.4 Clinicians describe it in a very operational and timed manner, stating that early action can prevent neuronal injuries from happening. They define SE as a continuous attack that exceeds 5 minutes or 2 or more separate attacks with incomplete recovery of consciousness between attacks.5 The SE is of 2 types: the convulsive type (CSE), which is the commonest, and the non-convulsive type (NCSE), which accounts for only 6% of the cases.6The main risk factors for SE are listed in many studies, with acute febrile illness being listed as a major cause. One study conducted in Japan found that prolonged febrile seizure is the cause of SE for 81.6% of the cases, while the causes for 18.4% of the cases were epilepsy, encephalopathy/encephalitis, and meningitis.7 Another study was carried out at Ayub Medical College with 125 patients, where most of the cases were caused due to acute febrile illnesses.8 In a cohort study conducted by the Specialized Children Hospital’s Pediatric Emergency Department at Cairo University, the acute symptomatic (AS) causes were the main etiologies. In that study, most AS cases (61%) were caused due to central nervous system (CNS) infection; the other causes were metabolic, hemorrhagic stroke, and neoplasim; most of them were infants aged less than one year at the SE onset (67%) and suffered from refractory seizure (86%) in which the seizure lasts for more than 60 minutes.9 Another main cause of SE was epilepsy; as mentioned in previous study in 1994, most SE patients have a history of epilepsy. Febrile seizures, meningitis, encephalitis, and metabolic disease were the other etiologies of SE in the study.10 However, only few studies include pediatric cases from Riyadh city of Saudi Arabia11 and a guideline management,12 and only a few and old (2002 and less) studies on SE pediatric patients in Jeddah,13,14 and thus making our study a significant contribution in this field. The study objectives are to identify the most common SE risk factors to prevent them in the future.     

Neurodevelopmental and epilepsy outcomes of patients with infantile spasms treated in a tertiary care center

Objectives:To assess the neurodevelopmental and epilepsy outcomes in children with infantile spasms (IS).Methods:A retrospective chart review of all patients with infantile spasms admitted to King Khalid University Hospital (KKUH), Riyadh, Saudi Arabia between January 2000 and December 2017. Infants who were diagnosed to have IS as per the International League Against Epilepsy (ILAE) definition were included in this study. Patients who lost follow-up and those who did not receive treatment at KKUH were excluded.Results:Total of 53 patients were included and categorized into unknown, cryptogenic and symptomatic type of IS. The majority had symptomatic etiology (71.7%). Type of etiology and delay in initiation of treatment were significant predictors of motor and cognitive outcomes, but not seizure control. Patients with unknown IS, who were diagnosed earlier (0.72-month), had better neurodevelopmental outcomes. Vigabatrin in combination with either Adrenocorticotropic hormone (ACTH) or Prednisolone showed better seizure control in comparison to monotherapy and other combination modalities.Conclusion:Neurodevelopmental outcomes of IS are strongly associated with the underlying etiology. Early initiation of treatments had a favorable cognitive and motor outcome. Early response to combination therapy with resolution of spasms and hypsarrhythmia had better seizure outcomes. However, motor and cognitive outcomes were not affected by the response to the combination therapy.

Infantile spasms (IS) is a rare form of epileptic encephalopathy characterized by spasms and hypsarrhythmia on the electroencephalogram (EEG).1 IS is diagnosed at 6 months of age on average.2 There are no reports on the incidence of IS in Saudi Arabia. International estimates put the figure at 1:6,000 – 1:4,000 live births. Studies suggest that IS constitutes 2% of childhood epilepsies, and a quarter of epilepsy cases are seen during the first year of life.3 The etiology of IS is divided into prenatal, perinatal, or postnatal disorders.3 Genetic defects associated with IS are increasingly being understood. Tuberous sclerosis is the most common disorder associated with IS and constitutes 10-30% of symptomatic IS. It is an autosomal dominant disorder caused by mutations in TSC1 and TSC2 genes, with variable manifestations, including cardiac and renal tumors, cutaneous malformations, and seizures.4 Mutations in the ARX gene and cyclin-dependent kinase-like protein 5 (CDKL5), 14q12 duplications harboring FOXG1, STXBP1, and PLCB1 have been also implicated in IS.5-8 Other prenatal causes include hydrocephalus, hydranencephaly, Trisomy 21, Hypoxic-ischemic encephalopathy, congenital infections, and trauma. IS can also occur secondary to a perinatal or postnatal disorders, including meningitis, trauma, encephalitis, intracranial hemorrhage, and inborn errors of metabolism.9When there is no clear cause of IS identified, IS can be labeled as unknown or cryptogenic. Uunknown IS is characterized by normal development prior to the onset of IS. Cryptogenic IS, on the other hand, is diagnosed when no known etiology is determined, but prior developmental delay has occurred.10Neurodevelopmental regression is characteristic of IS, and children with history of IS often have poor neurodevelopmental outcomes.11 In a cohort of 180 patient, 53% of infants with symptomatic IS have normal seizure status and cognitive development compared to 21.9% of infants with unknown IS.12The long-term survival of patients with IS thought to be poor and was related to the underlying condition, where unknown IS generally has a better prognosis than symptomatic IS.11 The aim of this study was to identify those patients and treatment factors that correlate with favorable neurodevelopmental and epilepsy outcomes in a tertiary hospital in Saudi Arabia.     

Association between craniovertebral junction abnormalities and syringomyelia in patients with chiari malformation type-1

Objectives:To assess the correlation between craniovertebral junction (CVJ) abnormalities and syringomyelia in patients with Chiari malformation type-1 (CM1).Methods:This was a retrospective study including patients with CM1. Identification of cases was done by searching a radiology database at a university hospital from 2012 to 2017. Patients were divided into 2 groups based on whether CVJ abnormalities were present (CVJ+) or absent (CVJ-). The patients’ demographic and clinical data were reviewed. All magnetic resonance imaging studies were examined by a certified neuroradiologist.Results:Sixty-four consecutive patients with CM1 were included. The mean age was 24±17 years; 59% were females. The CVJ+ group had more female patients (p = 0.012). The most frequent CVJ abnormality was platybasia (71%), followed by short clivus (44%) and cervical kyphosis (33%). The CVJ abnormalities were more in Syringomyelia cases (p = 0.045). However, the results were not significant when hydrocephalus cases were excluded.Conclusion:Among CM1 patients, CVJ abnormalities were found more in patients with syringomyelia. Future studies with larger sample size are required to further study the correlation between CVJ abnormalities and both syringomyelia and hydrocephalus in CM1 patients.

Chiari malformation type-1 (CM1) was first described in 1891 by Austrian pathologist Hans Chiari.1,2 The CM1 is defined as caudal displacement of the cerebellar tonsils below the foramen magnum by 5 mm or more.3,4 This definition is merely a radiological definition. In the literature, the degree of cerebellar tonsil displacement varies from 3 mm to 5 mm.4 CM1 affects approximately 1% of the population and may involve a spectrum of neurologic involvement.2 Syringomyelia is reported in 25% of CM1 cases and may cause irreversible damage to the spinal cord with subsequent neurological deficits.5The pathophysiology of syringomyelia development in patients with CM1 has been extensively studied.6-9 Majority of publications indicated a block to the cerebrospinal fluid (CSF) circulation at the level of the craniovertebral junction (CVJ).8,9 Subsequently, the cerebrospinal fluid (CSF) accumulates and forms syringomyelia.8,9 The source of the CSF forming the syringomyelia can be from the fourth ventricle, the subarachnoid space (SAS), or from an extracellular source.8,9 From the 1950s to the 1970s, syringomyelia was believed to result from a difference in CSF pressure between the fourth ventricle and the central canal of the spinal canal.7 Theories to explain this mechanism include James Gardner’s water-hammer theory, Bernard Williams’ cranio-spinal pressure dissociation theory, and Ball and Dayan’s theory of tonsillar obstruction to the CSF pathway.10-12 In the 1990s, Oldfield believed that the mechanism of the development of syringomyelia involved abnormal CSF flow at the level of the foramen magnum.6,7 The descent of the cerebellar tonsils with each cardiac cycle produces a pressure wave in the spinal SAS, and thereby compresses the spinal cord from the outside and propagates a syrinx.7,9Several intradural and extradural factors have been implicated in the pathophysiology of CM1. Among the intradural factors identified during surgery for CM1, the presence of an arachnoid membrane obstructing the foramen of Magendie (i.e., an arachnoid veil) was significantly more frequent in patients with an associated syringomyelia.6 Other studies have examined whether the degree of tonsillar descent below foramen magnum in the CM1 patients is a contributing factor to the development of syringomyelia; however, the impact of tonsillar descent is controversial.6,9,13 Some studies have reported that the rate of syringomyelia increases as the degree of tonsillar herniation increases.6,9 As a possible explanation for syringomyelia development, other studies14,15 have addressed crowding of the SAS at the foramen magnum caused by tonsillar decent. In a study by Doruk et al15, the measured cervicomedullary compression ratio, defined as the ratio of the area occupied by the cerebellar tonsils to the area of the foramen magnum, was significantly correlated with the development of syringomyelia. This ratio could reflect the severity of blockage of the SAS at the CVJ and further supports the previously described mechanisms of syringomyelia development.9Extradural abnormalities at the CVJ are associated with CM1.15 Such pathologies include a small posterior cranial fossa, platybasia, basilar invagination, and short clivus.3,6,8,9 Several studies have examined the presence of CVJ abnormities in CM1 patients with and without syringomyelia.13,16-21 However, the presence of associated syringomyelia within the context of CM1 with and without CVJ abnormalities was inadequately highlighted. For instance, in one study,13 syringomyelia existed in 64% of CM1 patients with a short clivus, compared to 36% of CM1 patients without a short clivus. In order to further understand the relationship between the presence of one or more CVJ abnormalities and syringomyelia in CM1, the current study was conducted. Such knowledge will likely enhance the understanding of CVJ relationship with CM1 and may aid in the management of syringomyelia in such patients.     

Is cesarean section delivery associated with autism spectrum disorder?

Objectives:To investigate a correlation between birth by caesarean section and autism spectrum disorder (ASD).Methods:A case-control study with a case to control ratio of 1:2 was performed in Al-Madina Al-Munawarah city, Kingdom of Saudi Arabia during the year 2016. The cases were selected according to the eligibility criteria and children attending a well-baby clinic in the same hospital, were chosen as the control group subjects. Data was collected from the medical records and an interview-based questionnaire was administered to the mothers. The chi-square test was used for bivariate analysis and logistic regression to estimate the crude and adjusted odds ratios (ORs).Results:Eighty-seven cases of ASD and 174 control group subjects were included in the current study. Approximately 39% (n=34) of the 87 children with ASD were delivered by cesarean section compared to 21% (n=36) of the 174 children in the control group. After adjusting for potentially confounding factors, the adjusted OR was 2.9 (95% confidence interval [CI]: 1.57-5.35).Conclusion:An association between delivery by cesarean section and ASD was found in this study, in support of the findings of other studies. It is recommended that preventive measures are adopted to avoid unnecessary cesarean sections.

Autism spectrum disorder (ASD) comprises a range of conditions that are characterized by impaired social communication and interaction, as well as repetitive behavior. Autism spectrum disorder begins in childhood and continues into adulthood, leading to a significant psychological and financial burden on the caregiver and family. The worldwide prevalence of ASD is estimated to be 0.7%, although wide variability has been reported.1 In addition, it has been reported in several studies that the prevalence of ASD is increasing worldwide. A real increase in ASD cannot be excluded even though it might be explained by improvements in documentation and the diagnosis of milder cases.2,3The pathophysiology of the disease is not well understood but multifactorial etiology is suggested by the current evidence.1 Various genetic and environmental factors have been found to be associated with ASD, including, advanced paternal age and exposure to heavy metals such as lead and inorganic mercury.4 As is the case with many other diseases, it is believed that ASD is caused by an interaction between genetic and environmental factors rather than attributable to a single cause. Deoxyribonucleic acid (DNA) methylation, which can be influenced by diet, stress, drugs, or environmental chemicals, has also been suggested as the mechanism involved in this interaction.5Globally, cesarean section delivery is estimated to account for 19% of all births, ranging from 7% in Africa to 41% in Latin America and the Caribbean.6 An average of 4% global increase in ASD has been reported annually over the last few decades.6 Cesarean section is associated with various short and long-term health challenges, including respiratory morbidities,7 hospitalization for asthma,8 acute lymphoblastic leukemia,9 and neurodevelopmental impairment.10 Conflicting results have been reported in previous studies on an association between cesarean section delivery and the subsequent development of ASD in the infant.11-13 Thus, the current study objective was to investigate the association of birth by cesarean section and the risk of ASD.     

Frequency of antiepileptic drugs and response change in pediatric patients receiving 2 or more antiepileptic drugs

Objectives:To investigate the frequency of changes in antiepileptic drugs (AEDs) use, as well as concomitant changes in the degree of seizure control in pediatric patients, who are receiving 2 or more AEDs.Methods:A prospective follow-up study at Jordan University Hospital’s pediatric neurology clinics was conducted on epileptic pediatric patients receiving at least 2 AEDs between December 2013 and April 2014. Patients were followed for 12 months.Results:A total of 82 patients were included, with a mean age of 7.2±4.7 years. The mean number of AEDs received by patients at enrollment was 2.4±0.6, and 2.5±0.7 after follow-up. Most patients (63.4%) experienced no change in seizure control, and the majority reported at least one adverse drug reaction. Most patients received lower doses than recommended, both at the beginning and end of the study. During the year, only 3 patients (4%) were eligible for dose tapering, which would then be converted to monotherapy. Follow-up appointments average was 4.2±2.9 visits/patients in one year. The frequency of medication changes and dose adjustment was very low, about one-third (29.3%) of patients requiring no change in AEDs during any follow-up visits.Conclusion:During the one year follow-up study, most patients on polytherapy maintained their level of response to the AEDs, with minimal changes in their regimen despite frequent follow-up visits. Only a small percent could be converted to AEDs monotherapy.

Epilepsy is the most common neurological disorder in children.1 Despite the increase in the number of antiepileptic drugs (AEDs), about one third of patients with childhood epilepsy continue to have seizures.2 Successful management of epilepsy depends on many factors, including the cause of epilepsy, type of epilepsy, and AED-related issues, such as: dosing, compliance, side effects, monitoring, and pharmacokinetics.3,4 Most AEDs have a suboptimal patient tolerability profile (with a wide range of side effects); the second-generation AEDs may be better tolerated than the traditional AEDs, but are not actually more effective.5Due to the complexity of classifying seizures, as well as the difficulty in choosing the most appropriate AED, many patients must deal with drug therapy changes over the course of their treatment/management.5-7 It has been estimated that approximately 50% of patients who are newly diagnosed with epilepsy become seizure-free for at least 12 months on their first AED.7 However, about one-third receive 2 or more AEDs, while continuing to experience seizures.5 In general, patients requiring multiple AEDs to manage their epilepsy represent the more resistant group of patients. This group must be closely followed to optimize their AED regimen;8 as the change in drug therapy might be more likely, but improvement is expected to be limited. Cited reasons for lack of improvement include incorrect diagnosis, inappropriate choice of AED and/or dose, in addition to lack of adherence. Data regarding follow-up studies of pediatric patients on AED polytherapy is scarce.9,10 The aim of the current study is to conduct a short-term (12 months) follow-up study of the change in AEDs, as well as the response in a subgroup of pediatric epileptic patients receiving AED polytherapy.     

Incidence,risk factors,clinical presentation,and outcomes of hemorrhagic transformation in patients with ischemic stroke admitted to a tertiary hospital in Kingdom of Saudi Arabia

Objectives:To describe the incidence rate, clinical presentation, relevant risk factors, and outcome of hemorrhagic transformation (HT) among ischemic stroke patients.Methods:This retrospective study analyzed HT in patients with ischemic stroke admitted to King Abdullah Medical City from August 2011 to April 2019. Data were analyzed using SPSS. Patients characteristics, procedures, treatments, and outcomes were reported.Results:There were 504 ischemic stroke patients. The HT was detected in 38 patients (8%). The median age was 66.5 (54.3 -77.5) years, and 24 (63%) were males. HT was classified as hemorrhagic infarction (HI) in 22 patients (58%) while 16 patients (42%) were parenchymal hematoma (PH). The most common risk factors noted were: hypertension (74%), diabetes mellitus (DM) (66%), hyperlipidemia (63%) and ischemic heart disease (IHD) (61%). Nine patients (23.6%) developed HT after receiving thrombolytic therapy. Only one patient (3%) died of HT patients.Conclusion:HT accounted for (8%) of all ischemic stroke patients. Old age, DM, hypertension, and hyperlipidemia are frequently encountered with stroke patients who developed HT. Follow up CT brain could be of value and could identify HT early to get better outcomes.

Hemorrhagic transformation (HT) which is a spectrum of hemorrhage related to brain ischemia.1 The HT is a primary complications of acute ischemic stroke (AIS).2 Ischemia makes the cerebral vasculature fragile and more reliable to cause HT after AIS.3–5 HT increases both morbidity and mortality rate in the ischemic stroke patients.2 The HT affects the outcomes with potential severe short- and long-term effects.6 The incidence of HT is between 10–40% and depends on many factors.1,7,8 Most of HT occurs within 2 weeks of an ischemic stroke.5 Previous studies considered old age, hypertension (HTN), diabetes mellitus (DM), large infarct (>2 cm), reperfusion time, lower platelet count and treatment with thrombotic- or anticoagulant-therapies as risk factors.9–12 The most effective treatment for AIS according to previous studies is recombinant tissue plasminogen activator (r-tPA),13 however, it appears to increase the risk of symptomatic or asymptomatic HT.1 Previous studies also suggest that the outcome of HT patients be strongly associated with HT type hemorrhagic infarction (HI) (Petechiae) or parenchymal hematoma (PH) (a space-occupying lesion), PH was a significant predictor of both mortality and neurological deterioration.14 Thus, it is critical to understand HT and its characteristics especially in our population. This retrospective study was designed to describe the incidence rate, clinical presentation, and relevant risk factors of HT among ischemic stroke patients. Identifying such knowledge could improve the outcome and decrease the risk of HT in AIS patients.     

Prevalence and risk factors of myasthenia gravis recurrence post-thymectomy

Objectives:To evaluate the prevalence and the factors associated with recurrence of myasthenia gravis following thymectomy.Methods:Six electronic databases which reported on recurrence of myasthenia gravis following thymectomy and/or its risk factors from 1985 to 2018 were searched. Summary prevalence and risk values obtained based on the random effect models were reported.Results:Seventy (70) papers containing 7,287 individuals with myasthenia gravis who received thymectomy as part of their management were retrieved. The patients had a mean follow-up of 4.65 years post-thymectomy. The prevalence of myasthenia gravis recurrence post-thymectomy was 18.0% (95% CI 14.7–22.0%; 1865/7287). Evident heterogeneity was observed (I²=93.6%; p<0.001). Recurrence rate was insignificantly higher in male compared with female patients (31.3 vs. 23.8%; p=0.104). Pooled recurrence rates for thymomatous (33.3%) was higher than the rate among non-thymomatous (20.8%) myasthenia gravis patients (Q=4.19, p=0.041). Risk factors for recurrence include older age, male sex, disease severity, having thymomatous myasthenia gravis, longer duration of the myasthenia gravis before surgery, and having an ectopic thymic tissue.Conclusion:A fifth of individuals with myasthenia gravis experience recurrence after thymectomy. Closer monitoring should be given to at-risk patients and further studies are needed to understand interventions to address these risks.

Myasthenia gravis (MG) a rare clinical condition characterized by autoimmune abnormalities is also the commonest neuromuscular junction (NMJ) disorder.1 Its pathophysiology involves the production of abnormal antibodies which binds to nicotinic acetylcholine receptors at the NMJ of skeletal muscles leading to alteration and damage of the NMJ.1-2 The disease is common in young women, however, another peak in incidence may occur at the 6th or 7th decade of life mainly in men in some population; and it may exhibits no sex preference in others.2 Clinically, patients with MG develop varying levels of skeletal muscle weakness affecting the ocular, bulbar, oculo-bulbar system, respiratory system, and the extremities.1 The pattern and course of MG is complex, varying from early remission to acute exacerbation and even death.3Previous research has revealed a strong relation between MG and disorders affecting the thymus. About 40 to 70% of individuals with MG have thymic follicular hyperplasia, and 10 to 21% of them have thymoma.4-6 Also, 20-47% of individuals having a thymoma have already developed or will develop MG.6-7 Findings from the literature indicate that 40 to 90% of individuals with MG attained remission following thymectomy compared with 10 to 20% among individuals with MG treated with medications without any surgery.6,8 Also, a recent randomised controlled trial demonstrated that thymectomy for individuals with nonthymomatous MG demonstrated better treatment outcomes during a three-year period compared with pharmacological therapy alone.9 Thus, guidelines now recommend thymectomy as a key treatment approach for MG.10A number of systematic reviews and/or meta-analyses among individuals with MG have been carried out. Some of these reviews explored the differences in outcomes between thymectomy and conservative management of MG,11,12 others compared surgical approaches of thymectomy,13-15 or potential prognostic factors for remission among individuals with MG irrespective of histological type following thymectomy.3,16 None assessed recurrence of MG following thymectomy or its risk factors. The identification of patient factors which are associated with recurrence of MG following thymectomy is crucial for the development of targeted interventions to address challenges associated with the care of individuals with MG. This systematic review and meta-analysis aimed to estimate the post-thymectomy recurrence rates and to investigate the factors associated with recurrence of MG following thymectomy in individuals with MG.     

Clinical Presentation and outcome of acute disseminated encephalomyelitis in Saudi Arabia: Tertiary Center Experience

Objectives:To evaluate the clinical presenation of acute disseminated Encephalomyelitis (ADEM) in pediatric age group, treatments, and to asses the outcome at King Abdulaziz Medical City, Riyadh, Kingdom of Saudia Arabia.Methods:The medical records of all patients younger than 18 years of age with a diagnosis of ADEM and treated at King Abdulaziz Medical City from January 1996 to Decemeber 2016 were collected. A total of 20 patients were included.Results:Of 20 patients enrolled in our study, 13 (65%) were female. Autumn and summer were the most common seasons in which ADEM presented (60%); 19 (95%) patients had a history of preceding viral illnesses. The most common neurological deficits on presentation were weakness (85%), ataxia (45%), and nystagmus (45%). Cortical and subcortical lesions (60%) were the most common finding on cranial magnetic resonance imaging. Seventeen patients (85%) received steroid only. Only 16 patients continued with follow-up, with a mean duration of 7 months. All 16 patients improved: 11 patients were recovered and 5 patients still had a neurological deficit at the clinic visits. No patient had relapsed.Conclusion:Most of the patients in this case series have an excellent outcome and attended follow-up visits and no disease relapses were identified. Further exploration of the disease is recommended.

Acute disseminated encephalomyelitis (ADEM) is a demyelinating disorder of the white matter in the central nervous system (CNS) that is caused by an immune-mediated monophasic inflammatory attack. The incidence is higher in the pediatric age group, varying worldwide from 0.3-0.6 per 100,000 children per year.1,2 The pathogenesis in ADEM is not fully understood; the existing evidence suggests that the disease results from a reaction to myelin-derived antigens triggered by immunization or infection.3 Preceding vaccination or infection has been reported in 67% of cases in multiple cohort studies.4 The ADEM has been reported to occur more commonly in winter and spring because of the increased likelihood of infection at these times.5The ADEM has a wide range of clinical presentations. Encephalopathy is usually the first clinical sign and develops suddenly, with alterations in consciousness, behavioral changes, or postictal symptoms that are unexplained by fever.6 From 2 to 8 days, the clinical presentation progressively worsens and deficits are maximized. Radiological findings are distinctive. The most common presenting feature on MRI is the presence of multiple bilateral T2-enhancing supratentorial white matter lesions. Accompanying lesions are often present in the thalamus and/or basal ganglia (40% of cases) and the brainstem and/or cerebellum (45% of cases).7-13Most patients will make a good recovery after ADEM, though it usually takes 4-6 weeks. At follow-up, approximately 60-90% of individuals have minimal or no neurological deficits.4,6,14 The relapse rate for ADEM is between 2-29%.15 As it is a very uncommon disease worldwide and in Saudi Arabia, data on clinical presentation and outcome of ADEM are lacking. To address this information gap, we have explored the clinical features and patterns of ADEM in children and young people in Saudi Arabia.     

The potential role of nutritional components in improving brain function among patients with Alzheimer’s disease: a meta-analysis of RCT studies

Objectives:To find out the potential role of nutritional components in improving brain function among patients with Alzheimer’s disease (AD).Methods:The correlation between nutrition and cerebral function in cases of AD has been the focus of 19 prospective randomised controlled trials (RCTs) with a combined research sample of 2297 patients. These RCTs are subject to systematic review and meta-analysis in the current paper.Results:Findings showed that chain-free secondary saturated fatty acids (SFA) and trans fatty acids (TFA) occurred in higher concentrations in AD patients’ brains than in controls. Furthermore, neuroinflammation was caused by remodelling of the lipid membrane and AD patients’ cognitive function was impacted by alterations in tyrosine, tryptophan, purine, and tocopherol pathway metabolomics. Moreover, in cases of mild-to-moderate AD, reduction in functionality was induced by administration of alpha-tocopherol for more than 12 months. Consumption of Souvenaid helps in synaptic synthesis, which enhances functional connectivity. Furthermore, consumption of the B vitamins folate, cobalamin and pyridoxine at dosages of 0.8 mg, 0.5 mg and 20 mg per day, respectively, over a period of one year resulted in lower plasma tHcy levels and brain atrophy.Conclusion:Chain-free SFA and TFA occur in greater amounts in the brains of individuals with AD than in those without AD.

Life expectancy has recently increased enormously throughout the world, owing to development in medical sciences. As a result, the ageing population has expanded quickly, causing a phenomenal rise in the prevalence of late-life cognitive diseases like AD and vascular dementia (VaD).1-3 Besides impacting cognition in ageing individuals, causing the brain to become atrophied and disrupting learning, cognitive, reasoning and communication capabilities, such conditions are also a significant burden from a social and economic perspective.4 Dementia occurs in 5-8% of people older than 65, 15-20% of those older than 75 and 25-50% of those older than 85 years of age.5 Age, gender, head trauma and CVD risk factors (e. g. cardiac disease, diabetes, high blood pressure, depression, high cholesterol, sedentarism, smoking, alcohol drinking) are among the known sporadic AD risk factors that are not of genetic origin.6-8The creation of medication capable of deferring AD onset by disrupting and mitigating Aβ synthesis has been the aim of a number of clinical research trials and empirical work and has attracted ample annual investment from pharmaceutical companies. Even though such medication is yet to be formulated, drugs for symptom management do exist.9 Thus, the approach toward drug development for AD, as well as the therapeutic role of nutrition in preventing AD, need to be reconsidered.Evidence has been produced that AD risk and progression are diminished by diet-related components like antioxidants,10,11 vitamins,12-14 polyphenols,15,16 and omega-3 fatty acids.17,18 By contrast, saturated fatty acids19 and simple carbohydrates20 are considered to increase likelihood of AD development.21 The RCTs carried out in the period 2010-2018 were reviewed in this paper to investigate whether AD patients’ cognitive function can be enhanced based on nutritional constituents. To this end, a meta-analysis was conducted to establish the extent to which cerebral function in AD cases was influenced by nutrition-based treatments. Furthermore, subgroup meta-analyses were also carried out to determine conformance to nutrition plans, proportion of deaths due to general causes and AD, respectively, body weight (BW), lean body mass (LBW), life expectancy, quality of life (QoL), and development of additional neurodegenerative diseases.     

The role of the family in early intervention of preterm infants with abnormal general movements

Objectives:To determine the effect of family-based intervention on motor function in preterm infants.Methods:This study was designed as a randomized controlled trial between August 2015 and September 2016. Forty-two preterm infants were randomized and split equally between the family-based intervention group, composed of a physiotherapeutic and a familial component (8 males, 8 females; mean age 91±3.09 days), and the traditional early intervention group (8 females, 8 males, mean age: 91.06±2.4 days). Both groups received a treatment program based on a neurodevelopmental approach during 3- to 12-months-old. The groups were evaluated at corrected ages of the third, sixth, ninth, twelfth, and 24th months using the Bayley Scale of Infant and Toddler Development, Third Edition (Bayley-III).Results:Within-group changes over time were statistically significant using multivariate tests of fine motor (Multivariate analysis of variance (MANOVA); F=1515.27, p<0.001) and gross motor (MANOVA; F=1950.59, p=0.001) development. However, there was no interaction between groups in fine (MANOVA; F=0.027, p=0.872) and gross motor development (MANOVA; F=0.022, p=0.883).Conclusion:The early intervention approaches might support fine and gross motor function development in preterm infants in the first year of life.

There is growing evidence that the first year of life is critical for brain development.1,2 The neuronal differentiation process, including the formation of dendrites and axons, as well as the production of neurotransmitters and synapses, is especially active during the prenatal period and continues to be active postnatally.2,3 Myelination starts in the second trimester of pregnancy and progresses rapidly in the first year of life.1,4 Recent studies suggest that interventions during infancy, when high plasticity is observed in the brain, might be more effective than interventions during childhood.5,6 Early diagnosis of infants at high-risk for major developmental disorders, such as cerebral palsy (CP) or minor motor and neurological dysfunction,7,8 is therefore important in providing appropriate interventions.9 Even if early interventions cannot change the physical outcome for infants with neurodevelopmental disorders, intervening with these high-risk infants helps to decrease secondary musculoskeletal system disorders and increase their functional abilities.10 However, it is still unclear which interventions are the most successful. The literature shows that early interventions effectively support cognitive development, but do not or only slightly affect motor development.5,11 With the increase in the survival of preterm infants, comprehensive follow-up programs have been developed to determine appropriate interventions to support them1. One of these, entitled Coping with and Caring for Infants with Special Needs (COPCA), was developed by Dierks et al.12 As a new family-based approach aimed to provide active involvement of the family in the intervention. This program’s approaches are based on both family education and neural group selection theory for infants. In a randomized controlled study, Hielkema et al13 demonstrated no difference in outcomes between Traditional Infant Physical Therapy (TIP) and the COPCA program for infants with an abnormal General Movements Assessment (GMA). A recent review by Hielkema et al14 demonstrated a medium level of evidence on early interventions and family education and called for high-quality studies on these subjects. Dirks and Hadders-Algra et al15 indicated that the importance of the role of the family in early intervention for infants with special needs has increased, and high-quality studies are now required to investigate the effect of family-based care.In addition to them, the quality of mother-infant interaction is one of the most important aspects of normal development.16 In comparison with mothers of full-term infants, mothers of preterm infants have a higher risk of postpartum depression after infants’ discharge.17 This might be caused the effect of premature birth and maternal separation (with prolonged stay in the Neonatal Intensive Care Unit) on hormones in both the mother and infant, which are crucial for managing the adaptive maternal behavior and emotional changes.18 In a randomized controlled trial, Hane et al16 investigated the impact of Family Nurture Intervention (FNI) to improve the developmental trajectories via increasing emotional connection between mothers and their premature infants. These authors proved that infants in FNI had increased cognitive and language scores on the Bayley-III at 18-months-old and decreased risk of attention problems, autism spectrum disorders, and postpartum depression of mother.16 In the other valuable study, Myer et al19 showed an improvement in the frontal cortical brain region (which is responsible for attention, behavior adaptation and cognitive development) in preterm infants that received FNI. Also, Welch et al20 demonstrated greater developmental changes and increased brain activity between brain regions in the FNI group. These studies promote the importance of the mother-infant relationship for normal neurodevelopmental processes. Based on these results, integrating the mothers in early intervention programs is essential for physiotherapy approaches.In the literature, many studies investigated the effect of the early intervention approaches by comparing the traditional infant physiotherapy on infants’ motor development.21-23 However, these studies could not prove any significant effects on motor development after early intervention. The possible explanation of the absence of the differences in motor development between the experimental and control group might be the heterogeneity of interventions, less specificity of the assessment tools to present the changes in development, and the impact of the normal growth process of infants.6,13 It is, therefore, difficult to compare interventions based on randomized controlled trials.13 There is a need for high-quality research that investigates the effects of physiotherapy interventions on gross and fine motor development of the high-risk infants to determine more useful, inexpensive, and accessible interventions for mothers, infants, and clinicians. The present study aimed to determine the effects of a family-based COPCA intervention program on fine and gross motor function in preterm infants.