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.

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.

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.

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.

Movement Disorders Due to Selective Basal Ganglia Lesions with Uremia.

BACKGROUND: Basal ganglia (BG) lesions are rarely reported in patients with uremia and may manifest by movement disorders. However, their exact incidence and pathogenesis have not been extensively studied. This study aimed to determine the frequency, types, risk variables (clinical, laboratory, and imaging), and manifestations of BG lesions with uremia and patients' neurologic outcomes. METHODS: This observational study included 70 adults (mean age: 45.87 ± 3.36 years; duration of uremia: 5.5 ± 1.5 years). They underwent extensive evaluations (clinical, laboratory, and neuroimaging) and had prospectively evaluated clinically every 3 months for 2 years. Repeated magnetic resonance imaging (MRI) brains were done to patients with movement disorders and correlated with their neurologic outcomes. RESULTS: BG lesions were found in 15 patients (21.4%) and 6 (8.6%) had movement disorders [Parkinsonism (n = 4), choreo-dystonia (n = 1) and dystonia (n = 1)] after the onset of uremia (mean = 10 months). There were no characteristic risk variables that distinguished patients with movement disorders from those without. Five developed movement disorders prior to the period of the study and one was de novo. The majority was females and had diabetes and higher frequencies of abnormal renal dysfunction, metabolic derangements, and white matter hyperintensities in MRIs. Movement disorders persisted in all patients despite the resolution of neuroimaging in three patients. CONCLUSIONS: There is no clear threshold for renal failure to result in movement disorders due to BG lesions. The clinical outcome is variables depending on each patient's comorbidities and complications. Persistent neuronal damage (due to uremic toxins/metabolic/nutritional and ischemic/microvascular factors) has been suggested as the cause of poor neurologic outcomes.

Psychogenic nonepileptic seizures in adults with epilepsy: a tertiary hospital-based study.

Objectives: Many studies describe and characterize psychogenic nonepileptic seizures (PNES) in high-income but few come from low/middle and low income countries.Design/methods: We aimed to determine the prevalence of PNES coexisted in adults with epilepsy and to characterize their semiology, comorbidities and predictors whether presented with epilepsy (n = 563) or alone (n = 73). Patients were recruited from a tertiary referral epilepsy clinic. Clinical suspicion and diagnosis were done by the neurologist based on histories and clinical cues. Psychiatric evaluation included structured psychiatric interviewing and assessment of symptoms of depression, anxiety and stress using Depression Anxiety Stress Scale (DASS 21).Results: The prevalence of PNES with epilepsy was 4.97% and diagnosed after a mean interval of 7.12yrs from onset of the first attack. Patients with PNES were predominantly females in their 2nd-3rd decades. Semiology of PNES included loss of consciousness, drop attacks, involuntary movements and speech arrest. Compared to patients with PNES coexisted with epilepsy, those with PNES alone were younger at presentation (p = 0.01) and age at onset (p = 0.002) and had frequent attacks (p = 0.001), psychosocial stressors and comorbid medical illnesses (p = 0.0001) and higher scores of depression, anxiety (p = 0.01) and stress (p = 0.001). In multivariate analysis, the significant predictors of high DASS scores with PNES were psychosocial stressors and comorbid medical conditions.Conclusions: The prevalence of PNES among adults with epilepsy is ∼5%. They are frequently misdiagnosed and treated as epilepsy. Specialist neurologists are more comfortable to diagnose patients with PNES. The multidisciplinary neurology and psychiatric assessments will help in the patient's therapeutic plan.

Synergistic Anti-Breast-Cancer Effects of Combined Treatment With Oleuropein and Doxorubicin In Vivo.

CONTEXT: Breast cancer is a leading cause of cancer fatalities among women worldwide. Of the more than 80% of patients who receive adjuvant chemotherapy, approximately 40% relapse. The majority of these patients die of disseminated metastatic disease, which emphasizes the need for new therapeutic strategies. OBJECTIVE: The study intended to investigate the anticancer effects of oleuropein (OL) and doxorubicin (DOX) individually and in combination on breast tumor xenografts and also to evaluate the molecular pathways involved. DESIGN: The research team designed in vivo (animal) and in vitro (cell culture) studies. SETTING: The study was performed in the College of Science of King Saud University in the University Center for Women Students (Riyadh, Saudi Arabia). ANIMALS: The study involved 40 female, nude mice (BALB/c OlaHsd-foxn1). INTERVENTION: The mice were injected subcutaneously with MDA-MB-231 human breast cancer cells. After the growth of tumors, the animals were randomly divided into 4 groups to receive intraperitoneal injections: (1) group 1 (control group)-dimethyl sulfoxide, (2) group 2 (intervention group)-50 mg/kg of OL, (3) group 3 (intervention group)-2.5 mg/kg of DOX, and (4) group 4 (intervention group)-1.5 mg/kg of DOX, immediately followed by 50 mg/kg of OL. The OL was extracted from Manzanillo olive trees (Olea europaea) grown in Tabouk, Saudi Arabia. OUTCOME MEASURES: The measures included the isolation and primary culture of the tumor xenografts, apoptosis analysis by annexin V, cellular lysate preparation, and immunoblotting. RESULTS: The volume of the tumor increased aggressively, reaching 173 mm3 in the control animals in a time-dependent manner. On the other hand, a sharp drop, to 48.7 mm3, in the volume of the tumor was observed with the 2 drugs combined, a more than 3-fold decrease. The effect was mediated through the induction of apoptosis via the mitochondrial pathway. The combined treatment downregulated the antiapoptosis and proproliferation protein, nuclear factor-kappa Β, and its main oncogenic target cyclin D1. Furthermore, it inhibited the expression of BCL-2 and survivin. This inhibition could explain the cooperative suppression of the proliferation of breast tumor xenografts and the induction of apoptosis by the combined effect of the compounds used. CONCLUSIONS: The key findings clearly indicate the synergistic efficacy of DOX with natural and nontoxic OL against breast tumor xenografts.

Cochlear Function in Adults with Epilepsy and Treated with Carbamazepine.

BACKGROUND: Epilepsy is a chronic medical disease and is associated with comorbid adverse somatic conditions due to epilepsy itself or its long-term treatment. OBJECTIVES: This study evaluated cochlear function in patients with idiopathic epilepsy and treated with carbamazepine (CBZ). PATIENTS AND METHODS: Included were 47 patients (mean age = 34.56 ± 7.11 years and duration of illness = 17.84 ± 7.21 years) and 40 healthy subjects. They underwent pure-tone audiometry and transient evoked otoacoustic emission (TEOAE) analyses. RESULTS: Hearing loss (mainly bilateral mild) was reported in one third of patients. Compared to controls, patients had lower TEOAE amplitudes at 1.0-4.0 kHz particularly at high frequencies (3 and 4 kHz). Significant correlations were identified between TEOAE amplitudes with CBZ dose (at 3 kHz: r = -0.554, p = 0.008; at 4 kHz: r = -0.347, p = 0.01), its serum level (at 4 kHz: r = -0.280, p = 0.045) and duration of treatment (at 3 kHz: r = -0.392, p = 0.008; at 4 kHz: r = -0.542, p = 0.001). CONCLUSIONS: Long-term CBZ treatment may result in cochlear dysfunction and auditory deficits.

Cognitive function in children with classic congenital adrenal hyperplasia.

Studies of cognitive function in patients with congenital adrenal hyperplasia (CAH) are few and controversial. This study aimed to investigate general intelligence and specific cognitive functions in children with salt wasting (SW) form of CAH and their relationship to demographic, clinical, and laboratory variables. This study included 36 children with classic 21 hydroxylase deficiency SW type of CAH (males = 12; females = 24; mean age = 15.6 ± 2.3 years). Intelligence quotient (IQ) and cognition were assessed using Wechsler Intelligence Scale for Children 3rd edition (WISC-III) and Stanford Binet Subsets Test version 4 (SBST4). Compared to controls, patients had lower mean full-scale (FS) IQ (P = 0.01) score, particularly performance IQ score (P = 0.001), and comprehension, pattern analysis, quantitation, bead memory, and memory for sentences of SBST4 (P = 0.05, P = 0.014, P = 0.001, P = 0.002, and P = 0.05, respectively). Lower IQ was observed in poorly controlled compared with well-controlled patients on medical treatment. Significant correlations were observed between FSIQ with age (r = - 0.810; P = 0.001), duration of treatment (r = - 0.887; P = 0.01), dose of glucocorticoids (r = - 0.463; P = 0.01), 17-OHP (r = - 0.543; P = 0.01) and testosterone (r = - 0.462; P = - 0.006) levels, and number of hyponatremic episodes (r = - 0.350; P = 0.05). In multivariate analysis, the independent risks of low FSIQ were the dose of glucocorticoids (OR = 1.14; 95% CI = 1.08-1.23, P = 0.0001), 17-OHP levels (OR = 2.25; 95% CI = 1.19-2.85, P = 0.01), and number of hyponatremic episodes (OR = 4.34; 95% CI = 2.05-5.15, P = 0.01).Conclusion: Patients with SW form of CAH may have lower IQ and cognitive deficits which may be related to the dose of glucocorticoids, androgen excess, and number of hyponatremic episodes. What is Known: • Congenital adrenal hyperplasia (CAH) is a group of inherited impairment of cortisol biosynthesis. • Studies of cognitive function in patients with congenital adrenal hyperplasia (CAH) are few and controversial. What is New: • Children with CAH may have lower intelligent quotient (IQ) and cognitive deficits. • Early hyponatremic episodes, overtreatment with glucocorticoids, and high androgen levels may be possible causative factors for the cognitive deficits.

Cardiac autonomic function in children with type 1 diabetes.

Cardiovascular autonomic neuropathy (CAN) is a major complication of type 1 diabetes (T1D). This study aimed to evaluate cardiac autonomic nervous system (ANS) function in children with T1D and its relation to different demographic, clinical and laboratory variable. This cross-sectional study included 60 children with T1D (mean age = 15.1 ± 3.3 years; duration of diabetes = 7.95 ± 3.83 years). The following 8 non-invasive autonomic testing were used for evaluation: heart rate at rest and in response to active standing (30:15 ratio), deep breathing and Valsalva maneuver (indicating parasympathetic function); blood pressure response to standing (orthostatic hypotension or OH), sustained handgrip and cold; and heart rate response to standing or positional orthostatic tachycardia syndrome or POTs (indicating sympathetic function). None had clinically manifest CAN. Compared to healthy children (5%), 36.67% of children with T1D had ≥ 2 abnormal tests (i.e., CAN) (P = 0.0001) which included significantly abnormal heart rate response to standing (POTs) (P = 0.052), active standing (30:15 ratio) (P = 0.0001) and Valsalva maneuver (P = 0.0001), indicating parasympathetic autonomic dysfunction, and blood pressure response to cold (P = 0.01), indicating sympathetic autonomic dysfunction. 54.55, 27.27 and 18.18% had early, definite and severe dysfunction of ANS. All patients had sensorimotor peripheral neuropathy. The longer duration of diabetes (> 5 years), presence of diabetic complications and worse glycemic control were significantly associated with CAN. CONCLUSIONS: The study concluded that both parasympathetic and sympathetic autonomic dysfunctions are common in children with T1D particularly with longer duration of diabetes and presence of microvascular complications. What is Known: • Cardiovascular autonomic neuropathy (CAN) is a major complication of type 1 diabetes (T1D). • Limited studies evaluated CAN in children with T1D. What is New: • CAN is common in children with T1D. • Cardiac autonomic functions should be assessed in children with T1D particularly in presence of microvascular complications.

Iron deficiency and cyanotic breath-holding spells: The effectiveness of iron therapy.

Aim: Frequent cyanotic breath holding spells cause fear and severe anxiety to parents. This study aimed to evaluate clinical, laboratory and treatment characteristics of children with cyanotic breath holding spells. Methods: Included were 180 children (mean age: 1.82 ± 0.53 years) with cyanotic breath holding spells. They were divided into three groups: with iron deficiency, with iron deficiency anemia and without iron deficiency. Blood hemoglobin (HB), ferritin and iron concentrations were measured at baseline and after 3 and 6 months of iron treatment. Results: The mean spell frequency was 24.57 ± 7.31/months, 83% had spells after the age of 1 year, 37% had daily spells, 16% had family history of spells, and 61% had Iron deficiency/Iron deficiency anemia (p = .001). No significant difference in the frequency of spells between children with iron deficiency and those with Iron deficiency anemia. Compared to patients without iron deficiency, there was significant reduction of spells frequency, increased hemoglobin, ferritin and iron levels after 3 and 6 months of iron therapy (p = .0001). Negative correlations were observed between spell frequency with hemoglobin (p = .001), ferritin (p = .0001) and iron (p = .001) levels. Conclusion: Not only Iron deficiency anemia but also iron deficiency alone without anemia is associated with a risk of high-frequency cyanotic breath holding spells. Iron therapy results in reduction in spells' frequency which was correlated with increasing ferritin and iron levels.

Genetic and phenotypic characterization of complex hereditary spastic paraplegia.

The hereditary spastic paraplegias are a heterogeneous group of degenerative disorders that are clinically classified as either pure with predominant lower limb spasticity, or complex where spastic paraplegia is complicated with additional neurological features, and are inherited in autosomal dominant, autosomal recessive or X-linked patterns. Genetic defects have been identified in over 40 different genes, with more than 70 loci in total. Complex recessive spastic paraplegias have in the past been frequently associated with mutations in SPG11 (spatacsin), ZFYVE26/SPG15, SPG7 (paraplegin) and a handful of other rare genes, but many cases remain genetically undefined. The overlap with other neurodegenerative disorders has been implied in a small number of reports, but not in larger disease series. This deficiency has been largely due to the lack of suitable high throughput techniques to investigate the genetic basis of disease, but the recent availability of next generation sequencing can facilitate the identification of disease-causing mutations even in extremely heterogeneous disorders. We investigated a series of 97 index cases with complex spastic paraplegia referred to a tertiary referral neurology centre in London for diagnosis or management. The mean age of onset was 16 years (range 3 to 39). The SPG11 gene was first analysed, revealing homozygous or compound heterozygous mutations in 30/97 (30.9%) of probands, the largest SPG11 series reported to date, and by far the most common cause of complex spastic paraplegia in the UK, with severe and progressive clinical features and other neurological manifestations, linked with magnetic resonance imaging defects. Given the high frequency of SPG11 mutations, we studied the autophagic response to starvation in eight affected SPG11 cases and control fibroblast cell lines, but in our restricted study we did not observe correlations between disease status and autophagic or lysosomal markers. In the remaining cases, next generation sequencing was carried out revealing variants in a number of other known complex spastic paraplegia genes, including five in SPG7 (5/97), four in FA2H (also known as SPG35) (4/97) and two in ZFYVE26/SPG15 Variants were identified in genes usually associated with pure spastic paraplegia and also in the Parkinson's disease-associated gene ATP13A2, neuronal ceroid lipofuscinosis gene TPP1 and the hereditary motor and sensory neuropathy DNMT1 gene, highlighting the genetic heterogeneity of spastic paraplegia. No plausible genetic cause was identified in 51% of probands, likely indicating the existence of as yet unidentified genes.

Effect of ginseng extract on the TGF-ß1 signaling pathway in CCl4-induced liver fibrosis in rats.

BACKGROUND: Liver diseases are major global health problems. Ginseng extract has antioxidant, immune-modulatory and anti-inflammatory activities. This study investigated the effect of ginseng extract on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. METHODS: Male Wistar rats were divided into four groups: control group, ginseng group, CCl4 group and CCl4 + ginseng group. Liver injury was induced by the intraperitoneal (I.P) injection of 3 ml/kg CCl4 (30% in olive oil) weekly for 8 weeks. The control group was I.P injected with olive oil. The expression of genes encoding transforming growth factor beta (TGF-ß), type I TGF-ß receptor (TßR-1), type II TGF-ß receptor (TßR-II), mothers against decapentaplegic homolog 2 (Smad2), Smad3, Smad4, matrix metalloproteinase 2 (MMP2), MMP9, tissue inhibitor matrix metalloproteinase-1 (TIMP-1), Collagen 1a2 (Col1a2), Collagen 3a1 (Col3a1), interleukin-8 (IL-8) and interleukin -10 (IL-10) were measured by real-time PCR. RESULTS: Treatment with ginseng extract decreased hepatic fat deposition and lowered hepatic reticular fiber accumulation compared with the CCl4 group. The CCl4 group showed a significant increase in hepatotoxicity biomarkers and up-regulation of the expression of genes encoding TGF-ß, TßR-I, TßR-II, MMP2, MMP9, Smad-2,-3, -4, and IL-8 compared with the control group. However, CCl4 administration resulted in the significant down-regulation of IL-10 mRNA expression compared with the control group. Interestingly, ginseng extract supplementation completely reversed the biochemical markers of hepatotoxicity and the gene expression alterations induced by CCl4. CONCLUSION: ginseng extract had an anti-fibrosis effect via the regulation of the TGF-ß1/Smad signaling pathway in the CCl4-induced liver fibrosis model. The major target was the inhibition of the expression of TGF-ß1, Smad2, and Smad3.

The relationship between valproate induced tremors and circulating neurotransmitters: a preliminary study.

Patients with epilepsy and on valproate (VPA) therapy may develop tremors as a common adverse effect; however, its exact mechanisms are unknown. We hypothesize that VPA-induced tremors may be related to the disturbances in dopamine (DA) and catecholamines (norepinephrine (NE) and epinephrine (E)) concentrations (which are also involved in VPA anticonvulsant effect). We aimed to determine the frequency and type of VPA-induced tremors and their risk factors and to investigate whether or not they are related to the plasma DA, NE and E concentrations. This study included 75 adults with primary epilepsy (mean age: 31.90 ± 5.62 years) and on VPA therapy for 10.57 ± 3.55 years and 40 matched healthy controls. Patients were divided according to the absence or presence of tremors. Blood samples were analyzed for DA, NE and E. Intermittent action tremors in both hands were reported in 31 (41.33%). Chronic standard VPA therapy, older age, longer treatment duration and higher serum concentrations of VPA are risk factors for tremors. None of the patients on controlled release VPA had tremors. Compared to controls, patients (without and with tremors) had lower DA (p = 0.0001) and NE (p = 0.01) concentrations. Compared to patients without tremors, patients with tremors had lower levels DA (p = 0.045) and NE (p = 0.01). Significant correlations were identified between DA with NE (r = 0.540, p = 0.001) concentrations and serum VPA with DA (r = -0.285, p = 0.045) and NE (r = -0.358, p = 0.01) plasma levels. We conclude that benign action tremors are common with standard VPA. Mechanisms underlying VPA-induced tremors may involve abnormalities of DA and NE neurotransmitters.

Homozygous nonsense mutation in SGCA is a common cause of limb-girdle muscular dystrophy in Assiut, Egypt.

INTRODUCTION: The genetic causes of limb-girdle muscular dystrophy (LGMD) have been studied in numerous countries, but such investigations have been limited in Egypt. METHODS: A cohort of 30 families with suspected LGMD from Assiut, Egypt, was studied using immunohistochemistry, homozygosity mapping, Sanger sequencing, and whole exome sequencing. RESULTS: Six families were confirmed to have pathogenic mutations, 4 in SGCA and 2 in DMD. Of these, 3 families harbored a single nonsense mutation in SGCA, suggesting that this may be a common mutation in Assiut, Egypt, originating from a founder effect. CONCLUSIONS: The Assiut region in Egypt appears to share at least several of the common LGMD genes found in other parts of the world. It is notable that 4 of the 6 mutations were ascertained by means of whole exome sequencing, even though it was the last approach adopted. This illustrates the power of this technique for identifying causative mutations for muscular dystrophies. Muscle Nerve 54: 690-695, 2016.

Indications and expectations for neuropsychological assessment in routine epilepsy care: Report of the ILAE Neuropsychology Task Force, Diagnostic Methods Commission, 2013-2017.

The International League Against Epilepsy (ILAE) Diagnostic Methods Commission charged the Neuropsychology Task Force with the job of developing a set of recommendations to address the following questions: (1) What is the role of a neuropsychological assessment? (2) Who should do a neuropsychological assessment? (3) When should people with epilepsy be referred for a neuropsychological assessment? and (4) What should be expected from a neuropsychological assessment? The recommendations have been broadly written for health care clinicians in established epilepsy settings as well as those setting up new services. They are based on a detailed survey of neuropsychological assessment practices across international epilepsy centers, and formal ranking of specific recommendations for advancing clinical epilepsy care generated by specialist epilepsy neuropsychologists from around the world. They also incorporate the latest research findings to establish minimum standards for training and practice, reflecting the many roles of neuropsychological assessment in the routine care of children and adults with epilepsy. The recommendations endorse routine screening of cognition, mood, and behavior in new-onset epilepsy, and describe the range of situations when more detailed, formal neuropsychological assessment is indicated. They identify a core set of cognitive and psychological domains that should be assessed to provide an objective account of an individual's cognitive, emotional, and psychosocial functioning, including factors likely contributing to deficits identified on qualitative and quantitative examination. The recommendations also endorse routine provision of feedback to patients, families, and clinicians about the implications of the assessment results, including specific clinical recommendations of what can be done to improve a patient's cognitive or psychosocial functioning and alleviate the distress of any difficulties identified. By canvassing the breadth and depth of scope of neuropsychological assessment, this report demonstrates the pivotal role played by this noninvasive and minimally resource intensive investigation in the care of people with epilepsy.

Atherosclerosis in epilepsy: its causes and implications.

Evidence from epidemiological, longitudinal, prospective, double-blinded clinical trials as well as case reports documents age-accelerated atherosclerosis with increased carotid artery intima media thickness (CA-IMT) in patients with epilepsy. These findings raise concern regarding their implications for age-accelerated cognitive and behavioral changes in midlife and risk of later age-related cognitive disorders including neurodegenerative processes such as Alzheimer's disease (AD). Chronic epilepsy, cerebral atherosclerosis, and age-related cognitive disorders including AD share many clinical manifestations (e.g. characteristic cognitive deficits), risk factors, and structural and pathological brain abnormalities. These shared risk factors include increased CA-IMT, hyperhomocysteinemia (HHcy), lipid abnormalities, weight gain and obesity, insulin resistance (IR), and high levels of inflammatory and oxidative stresses. The resulting brain structural and pathological abnormalities include decreased volume of the hippocampus, increased cortical thinning of the frontal lobe, ventricular expansion and increased white matter ischemic disease, total brain atrophy, and ß-amyloid protein deposition in the brain. The knowledge that age-accelerated atherosclerosis may contribute to age-accelerated cognitive and behavioral abnormalities and structural brain pathologies in patients with chronic epilepsy represents an important research path to pursue future clinical and management considerations.

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.