The effect of anticholinergic drugs on cognition of patients with Parkinson's disease: a cohort study from the Egyptian population.

BACKGROUND: Cognitive dysfunction is a non-motor manifestation of Parkinson's disease (PD). We aimed to determine the frequency and patterns of cognitive dysfunction in treated patients with PD and their predictors. RESEARCH DESIGN AND METHODS: This study included 80 patients (male = 48; female = 32) and 30 healthy individuals. They underwent neuropsychiatric evaluations. Measurements included Beck's depression inventory - II (BDI-II), mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA). RESULTS: Patients had mean age of 55.56 ± 9.06 yrs, duration of PD of 4.86 ± 2.71 yrs and Hoehn and Yahr Scoring of 2.19 ± 0.89. They were on levodopa/carbidopa therapy and adjuvant therapy with benztropine mesylate, an anticholinergic drug, (n = 51) or amantadine sulfate, a dopaminergic drug, (n = 29). Sixteen (20%) had moderate depressive symptoms. Mild and moderate cognitive impairments were reported in 38.8% and 28.8% (by MMSE) and 46.3% and 31.3% (by MoCA). Patients had lower global cognitive scoring (p = 0.0001) and scorings of different cognitive functions (naming, attention, language, abstraction, memory and orientation) than controls. Patients treated with benztropine had lower cognition than with amantadine. Correlation analyses showed that lower cognition was only associated with chronic PD and its treatment (p = 0.0001). CONCLUSIONS: Cognitive dysfunction is common with PD (77.5%) particularly with anticholinergic drugs. De-prescription of anticholinergics is recommended for patients with PD.

The effect of epilepsy and antiseizure medications on cardiac autonomic functions in children with epilepsy.

BACKGROUND: Autonomic manifestations have been frequently studied in adults with epilepsy. Here, we evaluated cardiac autonomic (ANS) functions in children with epilepsy in the interictal period and determined the risks for their dysfunctions. RESEARCH DESIGN AND METHODS: This study included 60 patients (boys = 25; girls = 35 age: 14.53 ± 2.54 yrs) and 25 controls. Patients were well-controlled on antiseizure medications (ASMs). The battery of testing included measuring resting heart rate (HR) and blood pressure (BP), 30:15 ratio, HR variability (HRV) response to deep breathing, Valsalva ratio and BP changes in response to standing, isometric exercise and cold. RESULTS: Dizziness was reported in 25%. Autonomic dysfunctions were found in 45% (n = 27). Manifestations included high frequencies of abnormal 30:15 ratio (22%), HRV responses to deep breathing (45%), Valsalava ratio (45%), and BP responses to standing (35%), isometric exercise (27%) and cold (27%), indicating parasympathetic and sympathetic hypofunctions. There were positive correlations between parasympathetic and sympathetic dysfunctions. Logistic analysis showed that the durations of epilepsy and ASMs therapy were associated with ANS dysfunctions [95% CI: 0.895-4.719, p = 0.004]. CONCLUSIONS: Parasympathetic and sympathetic autonomic hypofunctions are common in children with epilepsy. This could be due to the depressant effect of sodium channel blocker ASMs on central and/or cardiac autonomic systems.

The effectiveness of cerebrolysin, a multi-modal neurotrophic factor, for treatment of post-covid-19 persistent olfactory, gustatory and trigeminal chemosensory dysfunctions: a randomized clinical trial.

BACKGROUND: This trial aimed to monitor the outcomes of persistent post-covid-19 smell and taste disorders after cerebrolysin therapy, a NTF, and olfactory and gustatory trainings. RESEARCH DESIGN AND METHODS: This was a prospective randomized trial. It included 250 patients (male = 93, female = 157; age: 31.3 ± 8.9 years). Patients were randomized into group 1 (n = 150): received cerebrolysin [5 ml/d (IM), 5d/week] and practiced olfactory and gustatory trainings, and group 2 (n = 100): practiced olfactory and gustatory trainings only, for ≥ 8-24 weeks. Measures of outcomes were: a clinical questionnaire; sniffin' odor, taste and flavor identification tests; and global rating scales for smell and taste. RESULTS: The duration of disorders was 11.7 ± 3.7mo (range: 6-24mo). The majority (n = 167; 66.8%) developed parosmia within months (3.6 ± 2.7mo) after anosmia. Objective testing showed anosmia in all and taste, flavor, and trigeminal sensory losses in 18% (n = 45). Analyses for secondary outcome were done on 202 patients (group 1 = 130; group 2 = 72). Recovery was complete in 61.5% (n = 80) with cerebrolysin therapy and partial in 17% (n = 22). There was no recovery with trainings only. There were no predictors for recovery. CONCLUSIONS: Cerebrolysin had fast, promising, and constant effect, with cure rate of > 60%. This might be due to its ability to initiate and enhance neuronal regeneration and reorganization of sensory epithelia. TRIAL REGISTRATION: NCT04830943.

Evaluation of chronic idiopathic tinnitus and its psychosocial triggers.

BACKGROUND: The tinnitus susceptibility patterns in relation to different psychological and life stressors are unknown in different cultures. AIM: To determine the comorbid psychosocial factors and behaviors associated with tinnitus and the predictors for the increase in its severity. METHODS: Participants were 230 adults (males = 70; females = 160; mean age = 38.6 ± 3.3). They underwent audiograms, speech discrimination and masking testing, and neuropsychiatric evaluation. Measures used for assessment included tinnitus handicap inventory, depression anxiety stress scale 21 (DASS-21), perceived stress scale (PSS), and insomnia severity index (ISI). RESULTS: Patients had mean duration of tinnitus of 11.5 ± 2.5 mo. They had intact hearing perception at 250-8000 Hz and 95 (41.3%) had aggravation of tinnitus loudness by masking noise. Decompensated tinnitus was reported in 77% (n = 177). The majority had clinically significant insomnia (81.3%), somatic symptoms (75%) other than tinnitus and perceived moderate (46.1%) and high (44.3%) stress to tinnitus. The severe/extremely severe symptoms of depression, anxiety and stress were reported in 17.4%, 35.7% and 44.3%, respectively. Patients with decom-pensated type had significantly higher scores for ISI (P = 0.001) and DASS-21 (depression = 0.02, anxiety = 0.01, stress = 0.001) compared to those with compensated tinnitus. Psychiatric interviewing showed that 35.7% had non-specific anxiety disorder, 17.4% had major depression, and 19.6% fulfilled the criteria of somatization disorder. Multivariate analysis showed that the only independent predictors for tinnitus severity were the duration of tinnitus [odd ratios (OR) = 0.832, 95%CI: 0.640-1.158; P = 0.001] and PSS (OR = 0.835, 95%CI: 0.540-1.125; P = 0.001) scores. CONCLUSION: To the best of our knowledge, this is the first study in our culture to evaluate the causal relationship between psychological factors and tinnitus onset, severity and persistence. Tinnitus could be the earliest and dominant somatic symptom induced by life stressors and psychological vulnerabilities. Therefore, multidisciplinary consultation (psychologists, psychiatrists, and neurologists) is important to acknowledge among the audiologists and otolaryngologists who primarily consult patients.

Evaluation of children and adults with post-COVID-19 persistent smell, taste and trigeminal chemosensory disorders: A hospital based study.

BACKGROUND: Smell disorders are the most frequent persistent coronavirus disease 2019 (COVID-19) complications. AIM: To describe the patterns and characteristics of persistent smell and taste disorders in Egyptian patients. METHODS: Assessment was done to 185 patients (adults = 150, age: 31.41 ± 8.63 years; children = 35; age: 15.66 ± 1.63 years). Otolaryngology and neuropsychiatric evaluations were done. Measurements included: A clinical questionnaire (for smell and taste); sniffin' odor, taste and flavor identification tests and the Questionnaire of Olfactory Disorders-Negative Statements (sQOD-NS). RESULTS: Duration of disorders was 11.53 ± 3.97 ms (6-24 ms). Parosmia (n = 119; 64.32%) was developed months after anosmia (3.05 ± 1.87 ms). Objective testing showed anosmia in all, ageusia and flavor loss in 20% (n = 37) and loss of nasal and oral trigeminal sensations in 18% (n = 33) and 20% (n = 37), respectively. Patients had low scoring of sQOD-NS (11.41 ± 3.66). There were no specific differences in other demographics and clinical variables which could distinguish post-COVID-19 smell and taste disorders in children from adults. CONCLUSION: The course of small and taste disorders are supportive of the nasal and oral neuronal compromises. Post-COVID-19 taste and trigeminal disorders were less frequent compared to smell disorders. Post-COVID-19 flavor disorders were solely dependent on taste and not smell disorders. There were no demographics, clinical variables at onset or specific profile of these disorders in children compared to adults.

Idiopathic steno-occlusive disease with bilateral internal carotid artery occlusion: A Case Report.

BACKGROUND: Moyamoya disease (MMD) is a rare cause of acute stroke and transient ischemic attacks in children. We described clinical, diagnostic features and follow-ups of a young child with acute stroke. CASE SUMMARY: We report a 4-year-old girl with left hemiparesis after an acute ischemic stroke. Her history was also significant for repeated left or right focal motor seizures, generalized tonic-clonic convulsions and transient ischemic attacks. Her magnetic resonance imaging and computed tomography (CT) of the brain and magnetic resonance angiography, CT angiography and venography on the cerebral vessels revealed evidence of bilateral fronto-parietal ischemic infarctions, occlusion of the right and left internal carotid arteries started at its bifurcation and non-visualization of right and left anterior and middle cerebral arteries. There was evidence of progression in angiography manifested as development of collaterals from the basal perforating vessels, increase in the extent of large intracranial arterial stenosis/occlusion and extensive collateral circulation with predominance from the posterior circulation. Physical and neurological evaluation and comprehensive laboratory investigations excluded an obvious comorbid disease or risk factor for the child's condition. The diagnosis of MMD was highly suggested as a cause of the child's steno-occlusive condition. She was treated symptomatically with levetiracetam, an antiepileptic medication. Aspirin was prescribed for secondary prevention. Her clinical manifestations were improved during the three years of follow-up. Revascularization surgery was postponed. CONCLUSION: Up to our knowledge, this is the first report for MMD in a child in our country. The clinical improvement and the stabilization of the child's condition over the 3 years of follow-up could be attributed to the rapid and extensive recruitment of collaterals and absence of risk factors or comorbidities. Revascularization surgery is highly recommended.

Restless leg syndrome in patients with chronic kidney disease: a hospital-based study from Upper Egypt.

OBJECTIVES: Chronic kidney disease (CKD) is a common cause of restless leg syndrome (RLS). RLS is under-recognized, misdiagnosed and undertreated disorder in our locality. In this study, we aimed to determine the prevalence of RLS due to CKD and its predictors. METHODS: This cross-sectional study included 520 patients [male = 200; female = 320; age: 48.45 ± 3.63yrs; uremia duration: 6.44 ± 1.65yrs; CKD5D = 400; CKD3D = 120). RLS diagnosis was done by clinical interviewing according to International RLS Study Group criteria. All underwent detailed biochemical testing and iron and ferritin levels' measurements. Insomnia, depression and anxiety severities were assessed using insomnia sleep index (ISI), Beck Depression Inventory (BDI-II) and State-Trait Anxiety Inventory for Adults (STAI-AD) scales. RESULTS: RLS was found in 22.31% [ESKD = 26%, CKD3D = 10%]. Insomnia, depression and anxiety were found in 76.15%, 91.15% and 44.23%, respectively. Insomnia was correlated with depression (r = 0.488, p = 0.001) and anxiety (r = 0.360, p = 0.006) but not RLS. Multiple linear regression analysis showed that ESKD (OR = 3.8, 95%CI = 2.5-8.5, p = 0.001), inadequate dialysis (OR = 4.6, 95%CI = 3.5-8.6, p = 0.001), hyperparathyroidism (OR = 5.1, 95%CI 3.2-13.7, p = 0.0001) and peripheral neuropathy (OR = 5.6, 95%CI = 3.8-12.8, p = 0.0001) were independently associated with RLS. CONCLUSION: The prevalence of RLS with CKD is 22.31%. It is 2.6 times more frequent and severe with ESKD compared to CKD3D. It seems that RLS may occur early with CKD and becomes worse with progressive kidney impairment. Also, insomnia, depression and anxiety are common with CKD, however, their severities were not correlated with RLS. Predictors for RLS were ESKD, inadequacy of dialysis, hyperparathyroidism and peripheral neuropathy.

Vestibular function in children with generalized epilepsy and treated with valproate.

BACKGROUND: Studies that evaluated vestibular function with epilepsy are fewer than auditory studies. We assessed vestibular function in children with epilepsy in inter-ictal period. RESEARCH DESIGN AND METHODS: This cross-sectional study included 35 children with generalized epilepsy (boys=15; girls=20; age=11.20±1.21 years; epilepsy duration=3.54±1.80 years) and treated with valproate (VPA) and 24 healthy children. Vestibular evaluation was conducted using videonystagmography (VNG) and cervical vestibular evoked myogenic potentials (cVEMPs). RESULTS: Dizziness was the vestibular symptom in 22.86% of cases. Vestibular dysfunctions (VDs) were found in 65.71%. Manifestations of peripheral VD (65.71%) included unilateral caloric weakness and reduced cVEMP amplitudes. Manifestations of central VD (28.57%) included oculomotor abnormalities, positional nystagmus with normal calorics, and prolonged cVEMPs latencies. Significant correlations were found between VDs and duration of epilepsy and its treatment [r = -0.368, P=0.01] and VPA dose [r = -0.286, P=0.02] and level [r = -0.355, P=0.01]. Logistic regression analysis showed that duration of epilepsy and its treatment [OR = 3.55 (95% CI = 2.54-6.50), P=0.001] were independently associated with VDs. CONCLUSIONS: VDs are common in children with epilepsy. Bilateral peripheral VD was more common than central VD, suggesting an adverse effect of VPA. However, epilepsy cannot be excluded as a cause of central VD.

Peripartum depression and its predictors: A longitudinal observational hospital-based study.

BACKGROUND: Depression is a common problem in women in childbearing years due to burdens of motherhood and building a family. Few studies estimate the prevalence of antepartum depression compared to those in the postpartum period. AIM: To estimate the prevalence and the severities of peripartum depression and major depressive disorder and their predictors. METHODS: This is a longitudinal observation study. It included 200 women scoring ≥ 13 with the Edinburgh Postpartum Depression Scale, indicating presence of symptoms of depression. They had a gestational age of ≥ 6 wk and did follow-ups until the 10th week to 12th weeks postpartum. Information of women's reactions to life circumstances and stressors during the current pregnancy were gathered from answers to questions of the designed unstructured clinical questionnaire. Severities of depression, anxiety, and parenting stress were determined by the Beck Depre-ssion Inventory, State-Trait Anxiety Inventory for Adults, and Parenting Stress Index-Short Form, respectively. Psychiatric interviewing was done to confirm the diagnosis of major depression. Measuring the levels of triiodothronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) was done in both antepartum and postpartum periods. RESULTS: Out of 968 (mean age = 27.35 ± 6.42 years), 20.66% (n = 200) of the patients had clinically significant symptoms of depression and 7.44% had major depression. Previous premenstrual dysphoria, post-abortive depression, and depression unrelated to pregnancy and were reported in 43%, 8%, and 4.5% of the patients, respectively. Psychosocial stressors were reported in 15.5% of the patients. Antepartum anxiety and parenting stress were reported in 90.5% and 65% of the patients, respectively. Postpartum T3, T4, and TSH levels did not significantly differ from reference values. Regression analysis showed that anxiety trait was a predictor for antepartum (standardized regression coefficients = 0.514, t = 8.507, P = 0.001) and postpartum (standardized regression coefficients = 0.573, t = 0.040, P = 0.041) depression. Antepartum depression (standardized regression coefficients = -0.086, t = -2.750, P = 0.007), and parenting stress (standardized regression coefficients = 0.080, t = 14.34, P = 0.0001) were also predictors for postpartum depression. CONCLUSION: Results showed that 20.66% of the patients had clinically significant symptoms of depression and 7.44% had major depression. Anxiety was a predictor for antepartum and postpartum depression. Antepartum depression and parenting stress were also predictors for postpartum depression.

Vestibular function for children with insulin dependent diabetes using cervical vestibular evoked myogenic potentials testing.

BACKGROUND: Healthy vestibular system adjusts balance during static and dynamic conditions. This is important for normal development (standing up and walking). Vestipulopathies (central and peripheral) are common complications of diabetes in adult population. Related studies are scare in children with type 1 diabetes (T1D). AIM: To assess saccular function of otolith organ in children with T1D and predictors for its dysfunction. METHODS: Cervical vestibular evoked myogenic potential (cVEMP) was used for objective evaluation. RESULTS: The study included 40 patients (boys = 15; girls = 25). Patients had mean age of 13.63 ± 1.50 years, duration of diabetes of 5.62 ± 2.80 years, frequent attacks of diabetic ketoacidosis (55%) and hypoglycemia (30%), hyperlipidemia (20%), hypertension (12.5%) and peripheral neuropathy (40%). Dizziness was found in 10%. Compared to healthy children (n = 25), patients had prolonged cVEMP P1 and N1 latencies and reduced P1-N1 amplitude. Bilateral cVEMP abnormalities were found in 60% (vs 25% for unilateral abnormalities). Higher frequencies and severe vestibulopathies were found with chronic diabetes of > 5 years, hemoglobin A1c values > 7%, frequent diabetic ketoacidosis and hypoglycemic attacks and presence of dizziness. Regression analyses showed that predictors for prolonged P1 latencies and reduced P1-N1 amplitudes were only chronic diabetes (> 5 years) {odds ratio (OR) = 2.80 [95% confidence interval (CI): 1.80-5.33], P = 0.01; OR = 3.42 (95%CI: 2.82-6.81)} and its severity (hemoglobin A1c > 7%) [OR = 3.05 (95%CI: 2.55-6.82), P = 0.01; OR = 4.20 (95%CI: 3.55-8.50), P = 0.001]. CONCLUSION: Dysfunction or injury of the saccular macula and its pathways is prevalent in children with T1D. Optimum glycemic control is important to prevent diabetes related vestipulopathies.

Vestibular Function in Children with Type 1 Diabetes: Videonystagmography Testing.

BACKGROUND: Vestibular system is critical for maintaining balance and learning complex tasks. This study aimed to determine the frequencies, types, and predictors of vestibular dysfunctions (VDs) in children with type 1 diabetes (T1D) using videonystagmography (VNG). PATIENTS AND METHODS: This study included 65 patients (children with T1D = 40; controls = 25). The patients underwent VNG. RESULTS: Patients (boys = 15; girls = 25) had a mean age of 14.05 ± 1.82 years and duration of illness of 6.30 ± 2.84 years. The majority had frequent attacks of diabetic ketoacidosis (DKA) (65%) and hypoglycemia (40%). Dizziness was reported in 20%. VNG abnormalities were reported in 70% (n = 28), of them 71.43 and 28.57% had central and peripheral VDs, respectively. Dizziness was associated with peripheral VD. Compared to patients without VDs, those with VDs were older and had earlier age at onset and longer duration of diabetes (>5 years), higher levels of HbA1c (>7%), higher frequencies of DKA and hypoglycemic attacks, comorbid medical conditions, and diabetic complications. Multiple logistic regression analysis showed that presence of VNG abnormalities (VDs) was independently correlated with diabetes duration >5 years (odds ratio [OR] = 4.52 [95% confidence interval [CI] = 3.55-7.04], p = 0.001), HbA1c% levels >7% (OR = 3.42 [95% CI = 2.84-5.75], p = 0.001), and presence of hypoglycemic attacks (OR = 4.65 [95% CI = 2.85-7.55]). CONCLUSIONS: -VDs are prevalent in children with T1D and correlated with the duration and severity of diabetes and the occurrence of hypoglycemic attacks. Therefore, optimizing glycemic control and prevention and treatment of diabetic complications and comorbidities are important. Multidisciplinary follow-ups are required for early detection and management of diabetic VDs.

Scanning Electron Microscopy of Vitellogenic Oocytes and Spawned Eggs of the Portunid Crab Charybdis hellerii (Crustacea-Brachyura) (Milne Edwards, 1867).

BACKGROUND: The portunid crab Charybdis hellerii is an economically critical aquatic species in the Mediterranean region. Several investigators have reported scanning electron microscopy (SEM) observations on some crustacean's eggs' morphology. Going through the previous studies, knowledge regarding the morphology of C. hellerii. vitellogenic oocytes and spawned egg membranes are not available. AIMS AND OBJECTIVES: In the present study, an attempt has been made to describe the morphology and the structure of the membranes of vitellogenic oocytes and the newly spawned eggs to provide necessary information for further studies on the reproductive and evolutionary biology of the crab C. hellerii. MATERIALS AND METHODS: Samples of ripe pinkish orange ovaries of non-ovigarous females and the spawned incubated eggs of ovigerous females with orange and grey spawns were processed for scanning electron microscopy. The prepared samples were examined in a Zeiss DSM 940 scanning electron microscope. RESULTS: The present SEM study revealed that, vitellogenic oocytes are highly packed with yolk inclusions, which appear to be embedded in a definite acellular matrix and surrounded by a distinct chorion, which is pierced by several pores. The follicle cells appear polygonal in shape and interconnected through thin lateral projections and strongly associated with vitellogenic oocytes. The brooded fertilized eggs are attached through a marked stalk (funiculus) and surrounded by three distinct envelopes, which showed specific ornamentations and variations in their surface topography. The outer envelope coarsely wrinkled, while the middle envelope showed finely wrinkled ornamentation, and the inner envelope appeared with its characteristic spongy, porous appearance. CONCLUSIONS: This study denotes a significant difference between mature vitellogenic oocytes inside the ripe ovary and the spawned ova. The differences have been shown in the structure and external ornamentation of their surrounding membranes. Unlike the vitellogenic oocytes, the spawned ova were surrounded by three distinct layers, which are differ in their surface architecture. Such membrane architecture is species specific characteristic and has been thought to be an adaptive feature for brooded fertilized eggs to survive from stressful environmental conditions.

Biallelic variants in HPDL cause pure and complicated hereditary spastic paraplegia.

Human 4-hydroxyphenylpyruvate dioxygenase-like (HPDL) is a putative iron-containing non-heme oxygenase of unknown specificity and biological significance. We report 25 families containing 34 individuals with neurological disease associated with biallelic HPDL variants. Phenotypes ranged from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spasticity and global developmental delays, sometimes complicated by episodes of neurological and respiratory decompensation. Variants included bona fide pathogenic truncating changes, although most were missense substitutions. Functionality of variants could not be determined directly as the enzymatic specificity of HPDL is unknown; however, when HPDL missense substitutions were introduced into 4-hydroxyphenylpyruvate dioxygenase (HPPD, an HPDL orthologue), they impaired the ability of HPPD to convert 4-hydroxyphenylpyruvate into homogentisate. Moreover, three additional sets of experiments provided evidence for a role of HPDL in the nervous system and further supported its link to neurological disease: (i) HPDL was expressed in the nervous system and expression increased during neural differentiation; (ii) knockdown of zebrafish hpdl led to abnormal motor behaviour, replicating aspects of the human disease; and (iii) HPDL localized to mitochondria, consistent with mitochondrial disease that is often associated with neurological manifestations. Our findings suggest that biallelic HPDL variants cause a syndrome varying from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spastic tetraplegia associated with global developmental delays.

Behavioral assessment of children and adolescents with Graves' disease: A prospective study.

Previous studies have identified frequent comorbid neuropsychiatric disorders and conditions in adults with thyrotoxicosis. These studies are scarce or even lacking in pediatric population. This work aimed to study the behavior of children and adolescents with Graves' disease (GD). This study included 35 children with GD (boys = 15; girls = 25; mean age: 11.45±1.50yrs) and 40 healthy children (boys = 20; girls = 20; mean age: 12.54±1.62yrs). Behavior was assessed using Child Behavior Checklist (CBCL). Children with GD were assessed during periods of thyroid hormone elevation (active disease) and normalized thyroid hormones (with anti-thyroid drugs or ATDs). Compared to healthy children, patients during periods of thyroid hormone elevation (74.29%) and normalized thyroid hormones (31.43%) had higher frequencies of behavioral abnormalities and scorings of total CBCL scale (P = 0.01; P = 0.04, respectively) and its subscales' [Anxious/Depressed (P = 0.02; P = 0.04), Withdrawn/Depressed (P = 0.03; P = 0.04) and Somatic Complaints (P = 0.03; P = 0.127) and Social (P = 0.01; P = 0.225), Thought (P = 0.01; P = 0.128) and Attention (P = 0.01; P = 0.01) problems], indicating internalizing and externalizing problems. The majority of patients had at least two different behavioral problems. Marked improvement was found during period of normalized thyroid hormones (P = 0.001). Correlation analyses showed significant associations between total CBCL scoring and age at onset (P = 0.01; P = 0.001) and lower concentrations of thyroid stimulating hormone (TSH) (P = 0.001; P = 0.04) and higher concentrations of free thyroxine (fT4) (P = 0.01; P = 0.02), triiodothyronine (fT3) (P = 0.01; P = 0.03) and thyrotropin receptor antibodies (TRAbs) (P = 0.001; P = 0.01) during periods of thyroid hormone elevation and normalized thyroid hormones, respectively. Multiple linear regression analysis showed that "at presentation" lower concentrations of TSH (P = 0.001; P = 0.03) and higher concentrations of fT4 (P = 0.001, P = 0.01), fT3 (P = 0.01; P = 0.06) and TRAbs (P = 0.001; P = 0.001) were predictors of behavioral problems during periods of active disease and normalized thyroid hormones. We conclude that GD is associated with higher frequencies and severities of anxiety, depression and inattention during periods of thyroid hormone elevation as well as normalized thyroid hormones with ATDs. Therefore, early diagnosis and optimizing management are required to improve children's social life.

Behavioral assessment of females with congenital adrenal hyperplasia.

PURPOSE: Patients with congenital adrenal hyperplasia (CAH) have an increased risk of psychological/psychiatric symptoms and disorders. This study aimed to assess the behavior of girls with CAH and its independent risk variables. METHODS: This cross-sectional study included 55 girls with CAH due to 21-hydroxylase deficiency (mean age 12.64 ± 1.52 years; salt-wasting (SW) form = 20, simple virilizing (SV) form = 35). Psychiatric interviewing and the Strength and Difficulties Questionnaire (SDQ) (parent-reporting questionnaires) were used to assess behavior. RESULTS: Compared to controls (n = 60), patients had a high total SDQ score (P = 0.001) and emotional, conduct, and hyperactivity-inattention symptoms, peer relationship problems (P = 0.001 for all), and prosocial behavior (p = 0.01) subscale scores, indicating externalizing and internalizing behavioral problems. Severe emotional symptoms and poor disease control were found with SW compared to the SV form. Multiple linear regression showed that bone age (BA) (ß = 0.331, t = 3.608; P = 0.001) and 17-OHP (ß = 0.408, t = 4.220; P = 0.001), testosterone (ß = 0.348, t = 3.220; P = 0.001), and androstenedione (ß = 0.238, t = 2.487; P = 0.015) levels were independently associated with behavioral problems. CONCLUSION: Females with CAH had frequent and severe behavioral symptoms. Excess androgenization, which was in part due to suboptimal steroid therapy, was the cause of the behavioral problems. Therefore, early optimization of CAH management should be stressed to prevent psychological consequences.

Behavioral problems in children with primary monosymptomatic nocturnal enuresis.

BACKGROUND AND OBJECTIVES: Primary monosymptomatic nocturnal enuresis (PMNE) is a common distressing condition to children and parents. This study aimed to determine frequencies, severities and characteristics of behavioral problems with PMNE. METHODS: This cross-sectional study included 80 children with PMNE (age: 12.58 ± 1.24 yrs.; boys = 58, girls = 22) and 60 healthy children. Behavioral symptoms were assessed by Strength and Difficulties Questionnaire (SDQ). RESULTS: This study included 80 children (boys/girls ratio = 2.64:1) with PMNE. They had mean age of 12.58 ± 1.24 yrs. The majority (70%) had good response to medical treatment. Compared to controls, children with enuresis had higher frequencies of emotional, conduct and hyperactivity-inattention symptoms and peer relationship and prosocial problems and higher total (P = 0.001) and different subscales' scores of SDQ. There was an overlap of behavioral problems in 52.2% of children with nocturnal enuresis. Compared to children without behavioral symptoms, children with behavioral symptoms were significantly older at age at presentation (P = 0.046) regardless of gender, residence and type or response to medications. Multiple regression analysis showed that emotional [ß = 0.053 (95%CI = 0.037-0.084), P = 0.024] and hyperactivity-inattention symptoms [ß = 0.063 (95%CI = 0.028-0.097), P = 0.001] were significantly associated with enuresis independent to other problems. CONCLUSION: PMNE is associated with higher risk of behavioral problems particularly emotional and hyperactivity-inattention symptoms indicating externalizing and internalizing problems, therefore, the importance of early non-pharmacological or/and drug interventions. The comorbid behavioral disorders should be treated separately according to evidence-based recommendations to prevent persistence of enuresis and the development of psychiatric disorders in the future.

Evaluation of the effectiveness of valproic acid for treating cyanotic breath holding spells: A Pilot prospective study.

BACKGROUND: Cyanotic breath-holding spells (CBHS) are self-limited conditions among younger children. Frequent spells cause parents' fear and anxiety. Seizures, brain damage and sudden death have been rarely reported with BHS. Some reported spells' frequency reduction with iron or piracetam. We evaluated the effectiveness of valproic acid (VPA) to treat CBHS and predictors of improvement. METHODS: Participants were 90 children with CBHS (≥4/week) (age: 1.6±0.4yrs). They were treated with VPA (5 mg/kg/d). Follow-ups occurred after 3-≥6 months. Autonomic nervous system functions were evaluated. RESULTS: The majority (74.4%) had daily spells and 19% had ≥2 spells/d. Crying or anger provoked spells. Postural hypotension was found in 46.7%. They had normal electroencephalography and QT, QTc interval or QTd or QTcd and heart rate. Compared to controls, postural fall in systolic (>20mmHg) and diastolic (>10mmHg) blood pressures and mean arterial pressure (>10mmHg) were observed in 46.7%, 74.4% and 72.2% and miosis observed with 0.125% pilocarpine in 28.9% (P=0.001). Spells' frequency reduction (P=0.001) occurred within 3 months with VPA. The independent prdictors for spell' frequency reduction were reduction of anger and crying [OR=4.52(95%CI=2.35-6.04), P =0.01]. CONCLUSION: VPA therapy reduces CBHS' frequency. Mood improvement is a suggestive effective mechanism. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT04482764.

The Effect of Epilepsy and Antiepileptic Drugs on Cortical Motor Excitability in Patients With Temporal Lobe Epilepsy.

OBJECTIVES: Transcranial magnetic stimulation (TMS) has been used to assess cortical disinhibition/excitation with epilepsy and determine the degree of patients' response to antiepileptic drugs (AEDs). However, the results of studies are variable and conflicting. We assessed cortical motor excitability in adults with temporal lobe epilepsy (TLE). METHODS: The TMS parameters used for assessment were: resting (RMT) and active (AMT) motor thresholds, cortical silent period (CSP), and central motor conduction time (CMCT). RESULTS AND CONCLUSIONS: This study included 40 adults (males, 22; females, 18) with TLE with impaired awareness or to bilateral tonic clonic seizures (mean age, 32.50 ± 3.38 years; duration of illness, 6.15 ± 2.02 years) and on treatment with AEDs (valproate, 15; carbamazepine, 15; levetiracetam, 10]. The majority (62.5%) were seizure-free for ≥1 year on AEDs before TMS testing. All had normal brain magnetic resonance imaging except two, who had mesial temporal sclerosis. Comparing the entire patients with controls, patients had significantly bihemispheric higher RMT and AMT particularly over the epileptic hemisphere and shorter CSP and CMCT in the epileptic hemisphere. Shorter CSP and CMCT were observed in patients on valproate or carbamazepine and those who were uncontrolled on medications but not with levetiracetam. Significant correlations were identified between RMT and AMT (P = 0.01) and between CSP and CMCT (P = 0.001). We conclude that chronic TLE had increased cortical disinhibition in the epileptic hemisphere which can spread outside the epileptogenic zone despite the apparent control on AEDs. The TMS studies using CSP and CMCT may help future prediction of pharmacoresistance and, therefore, the need of combined AEDs with multiple mechanisms of action.

Cortical excitability in epilepsy and the impact of antiepileptic drugs: transcranial magnetic stimulation applications.

INTRODUCTION: Epileptic conditions are characterized by impaired cortical excitation/inhibition balance and interneuronal disinhibition. Transcranial magnetic stimulation (TMS) is a neurophysiological method that assesses brain excitation/inhibition. AREA COVERED: This review was written after a detailed search in PubMed, EMBASE, ISI web of science, SciELO, Scopus, and Cochrane Controlled Trials databases from 1990 to 2020. It summarizes TMS applications for diagnostic and therapeutic purposes in epilepsy. TMS studies help to distinguish different epilepsy conditions and explore the antiepileptic drugs' (AEDs') effects on neuronal microcircuits and plasticity mechanisms. Repetitive TMS studies showed that low-frequency rTMS (0.33-1 Hz) can reduce seizures' frequency in refractory epilepsy or pause ongoing seizures; however, there is no current approval for its use in such patients as adjunctive treatment to AEDs. EXPERT OPINION: There are variable and conflicting TMS results which reflect the distinct pathogenic mechanisms of each epilepsy condition, the dynamic epileptogenic process over the long disease course resulting in the development of recurrent spontaneous seizures and/or progression of epilepsy after it is established, and the differential effect of AEDs on cortical excitability. Future epilepsy research should focus on combined TMS/functional connectivity studies that explore the complex cortical excitability circuits and networks using different TMS parameters and techniques.