Asian Study of Cerebral Venous Thrombosis.

BACKGROUND/OBJECTIVE: Most of the studies and registries related to cerebral venous thrombosis (CVT) are reported from European countries and the United States. The objective of the present study is to identify risk factors, presentation, and outcome of CVT in Asian patients. METHODS: Asian CVT registry is a prospective multinational observational study that included patients (aged > 16 years) with symptomatic CVT. RESULTS: Eight hundred and twelve patients (59% women) from 20 centers in 9 Asian countries were included. Mean age of the patients was 31 years. Motor weakness in limbs was present in 325 (40%) patients. One hundred and eighty (22.1%) patients had a normal Glasgow coma scale (GCS) at presentation, and another 529 patients (65%) had GCS between 11 and 14. The rest (103; 13%) had a GCS of less than 10 at presentation. Permanent risk factors were present in 264 (33%) patients, transient in 342 (42%) patients, both in 43 (5%) patients and no risk factors were found in 163 (20%) patients. Anemia was present in 51%, use of oral contraceptive pills (OCP) was present in 12% women and a hypercoaguable state was present in more than 40% of those tested. One hundred and forty-three cases (18%) were in women who were either pregnant (18; 2%) or in the puerperium (up to 6 weeks postpartum; N = 125; 15%). A total of 86 (10.5%) patients were diagnosed with infection in any part of the body. The most common MRI finding was local brain edema or ischemia (53.3%) followed by hemorrhage (26.7%). Twenty-seven patients (3.3%) died during hospital stay. The mRS score at discharge was available for 661 (81%) patients. Of these, 577 (87.3%) had good functional outcome at discharge. Motor weakness at presentation, GCS of 9 or less and mental status disorder were the strongest independent predictors of mortality at last follow-up among patients with CVT. CONCLUSIONS: Important differences were identified as compared to western data including younger age, high frequency of anemia, low use of OCP, and high frequency of hypercoaguable states. Functional outcome at discharge was good.

Occurrence of Hashimoto's thyroiditis among the patients with Sydenham's chorea.

AIM: The purpose of this study was to examine the possible association of Hashimoto's thyroiditis (HT) with Sydenham's chorea (SC). MATERIALS AND METHODS: A total of 25 SC patients and 25 patients with the diagnosis of HT were included in the study. Neurological, cardiac, radiological abnormalities, clinical findings, and biochemical analysis were evaluated. RESULTS: Heart murmur as a result of mitral valve deformation was present in all SC group patients. No neurologic and cardiac abnormalities were noted in HT group. Serum thyroid-stimulating hormone (TSH), anti-thyroid peroxidase, and anti-thyroglobulin levels were found to be high in 4 patients of the SC group and called as SC with HT group. Significant elevation of serum TSH levels in SC with HT group (31.75 ± 3.71 µU/ml) was observed when compared to HT group (12.60 ± 4.24 µU/ml, p < 0.05). CONCLUSION: These results showed that HT can be occurred among the patients with SC with cardiac involvement.

Prevalence of resistant occipital lobe epilepsy associated with celiac disease in children.

PURPOSE: Celiac disease (CD) is a chronic, inflammatory autoimmune disorder caused by intolerance to ingested gluten. Increased frequency of CD has been reported in occipital lobe epilepsy. The aim of the present study is to investigate the frequency of CD among children followed up due to epilepsy and diagnosed with epileptic activity in the occipital lobe in at least one electroencephalography (EEG) test. METHODS: For this research, 90 pediatric epilepsy patients with epileptic activity in the occipital lobe were enrolled in the study group, while the control group comprised of 100 healthy children. In addition to the EEG examination, tissue transglutaminase (tTG) antibody was determined on duodenal biopsy. RESULTS: None of the healthy children in the control group was positive in terms of the tTG antibody test used to scan CD. In the group with epileptic activity in the occipital lobe, two patients out of 90 were tTG antibody positive. The seroprevalence was 1/45 (2.22 %) in this group. These two patients were diagnosed with CD based on the endoscopic duodenal biopsy. In these patients, the seizures were uncontrollable through monotherapy. CONCLUSIONS: Our results showed that the prevalence of CD is observed to be higher than the normal population among the patients with occipital lobe epilepsy. This type of seizure disorder seems to be more resistant to monotherapy, compared with other types of occipital epilepsy. Therefore, screening for CD is recommended in children with resistant epileptic activity in the occipital lobe.

Prevalence and clinical significance of antithyroid antibodies in children with immune thrombocytopenic purpura.

BACKGROUND AND OBJECTIVE: To determine the prevalence and the clinical significance of thyroid autoantibodies and their influence on treatment response in children with idiopathic thrombocytopenic purpura (ITP). PATIENT AND METHOD: We retrospectively analyzed the antithyroglobulin (anti-TG) and antithyroid peroxidase (anti-TPO) antibodies from the records of 151 ITP patients who were admitted to the Pediatric Hematology Department of Gaziantep University between 2009 and 2012. RESULTS: Anti-TPO and/or anti-TG was found positive in 38 (36.8%) of 103 patients whose thyroid autoantibody levels were measured. The comparison of positivity ratios of autoantibodies between acute and chronic ITP patients showed no significant difference. However, the separate comparison of each group of ITP patients with control group showed significantly high positivity ratios of autoantibodies in ITP patients. The initial mean platelet count of anti-TPO positive patients at diagnosis was significantly less than that of the negative patients (P = .008). One month after treatment, platelet count of anti-TPO positive patients was significantly less than that of the negative patients (P = .01). Moreover, the mean platelet counts of anti-TPO positive patients were significantly less than those of the negative patients after intravenous immunoglobulin treatment (P < .001). CONCLUSION: We demonstrated that the thyroid-autoimmune-diseases-related autoantibodies are frequently found in childhood ITP. Although no recommendation is found in international guidelines regarding screening for thyroid autoantibodies in patients with ITP, in view of the high incidence of antithyroid antibodies and their potential negative effect on treatment response, screening these patients for such antibodies would be recommended.

Pregnancy and puerperium-related strokes in Asian women.

BACKGROUND: Despite an increased risk of stroke in pregnancy and puerperium, the overall incidence of the condition in this population is low. Therefore, there is limited data pertaining to these patients particularly from Asian countries. Our objective was to describe the risk factors and outcomes of 110 pregnancy-related ischemic strokes from 5 Asian countries. METHODS: Data were collected by retrospective chart review in most cases and prospectively in the rest. Inclusion criteria for this subanalysis were women, pregnant or within 1-month postpartum, presenting to the study center with acute ischemic stroke (arterial or venous) confirmed by neuroimaging. Intracranial hemorrhages other than the ones associated with cerebral venous thrombosis or hemorrhagic infarct were excluded. Risk factors were diagnosed based on already published criteria. Outcomes were measured using modified Rankin score. Statistical analysis was done using Statistical Package for Social Sciences version 19.0. RESULTS: In all, 110 women with mean age of 27.94 years presented with pregnancy-related ischemic strokes; 58.2% of the strokes occurred postpartum and 49.1% were secondary to cerebral venous thrombosis. Venous strokes were significantly more likely to occur postpartum compared with arterial strokes (P=.01), to have abnormal "hypercoagulable panel result on admission" (P<.001), less likely to have traditional stroke risk factors (P<.001), to have hemorrhagic conversion of stroke (P<.001), and to have lesser stroke severity and better functional outcome at 3 months (P<.001 for each). CONCLUSION: Cerebral venous thrombosis is a significant contributor to pregnancy-related strokes in Asian women. Both traditional and pregnancy-specific risk factors should be addressed to control ischemic stroke risk in these women.

Ischemic stroke in young Asian women: risk factors, subtypes and outcome.

BACKGROUND AND OBJECTIVE: The objective of our study was to describe risk factors, mechanisms and outcome of young Asian women with ischemic stroke. METHODS: Twelve tertiary-care centers in 8 Asian countries participated. Women aged 15-45 years were included if they had an ischemic stroke supported by neuroimaging. Data on age, risk factor history, stroke mechanism and discharge status were collected. RESULTS: A total of 958 subjects were included, their mean age was 34 years. Large-vessel thrombosis comprised 24%, cerebral venous thrombosis 21%, cardioembolism 19% and small-vessel thrombosis 15%. The stroke risk factors included hypertension (29%), diabetes (14%), pregnancy (11%), valvular heart disease (10%) and cigarette smoking (3%). Anemia was found in 42%, and mortality was 4%; at discharge, 17% had modified Rankin score (mRS) >4 and 83% mRS 0-3. CONCLUSION: Unlike among Caucasians, large-vessel thrombosis, cerebral venous thrombosis and cardioembolism are common among young Asian women with stroke. A high proportion are pregnancy-related. More studies are needed.

Headache in Cerebral Venous Thrombosis: incidence, pattern and location in 200 consecutive patients.

We analyzed the incidence, pattern and location of headache in consecutive 200 patients with proven diagnosis of CVT to identify an association between localization of headache and site of sinus involvement. Headache was present in 136 (68%) patients. The duration of headache (reported in 128 patients) was reported as acute (1-3 days), 81 patients (60%); sub-acute (4-14 days), 33 patients (24%); and chronic (more than 14 days), 14 patients (10%). The quality of headache (reported in 72 patients) was reported as throbbing 12 (9%), band like 27 (20%), thunderclap 7 (5%), and other (pounding, exploding, stabbing, etc.) 26 (20%). The location of headache (reported in 101 patients) was reported as unilateral (one side of head) 48 (37%), localized (frontal, temporal, occipital, and neck) 25 (19%), and diffuse (whole head) 28 (20%). 43 (32%) patients had normal neurological examination (normal mental status, cranial nerves, motor and sensory examination with down going planters). 93 (68%) patients have abnormal findings on neurological examination including papilledema 29 (15%) patients, altered mental status 38 (19%), and focal neurological deficit 45 (22%) patients. There was no association between headache and presence of hemorrhage on CT and MRI (P = 0.1) or hydrocephalus (P = 0.09). There was no association between localization of headache and site of sinus thrombosis except sigmoid sinus thrombosis, where 17 out of 28 patients with involvement of sigmoid sinus alone or in combination with transverse sinus had pain in the occipital and neck region (P < 0.05). There was no association between lateralization of pain and site of thrombosis (P = 0.66).

Effectiveness Oral Theophylline, Piracetam, and Iron Treatments in Children With Simple Breath-Holding Spells.

Breath-holding spells (BHS) are common nonepileptic paroxysmal events in children. This is a retrospective study to compare the effectiveness of oral theophylline, piracetam, and iron treatments in children with simple BHS. A total of 146 children (75 girls and 71 boys) with simple BHS were included to this retrospective study. Children were divided into 4 groups: nontreated (no anemia and no treatment), oral theophylline (10 mg/kg/d as a single daily dose), piracetam (40 mg/kg/d in 2 divided doses), and elementary iron (3 mg/kg/d as a single daily dose) treatments. Iron therapy had been given only in children with iron deficiency anemia. Neurologic, cardiologic, and biochemical evaluations were performed for all children. The majority of the patients had cyanotic spells (83.6%). The frequency of attacks/month was markedly decreased with iron (58.8%) and theophylline (82.9%) treatments, but not with piracetam therapy (8.8%) and nontreated group (4.7%). Satisfaction of the parents/caregivers was found to be high in the theophylline group (P < .001). Our results showed that theophylline was the most effective therapy to decrease the frequency of simple BHS in children.

Cerebral venous sinus thrombosis in children: a multicenter cohort from the United States.

This study presents a large multicenter cohort of children with cerebral venous thrombosis from 5 centers in the United States and analyzes their clinical findings and risk factors. Seventy patients were included in the study (25 neonates, 35%). The age ranged from 6 days to 12 years. Thirty-eight (55%) were younger than 6 months of age, and 28 (40%) were male. Presenting features included seizures (59%), coma (30%), headache (18%), and motor weakness (21%). Common neurological findings included decreased level of consciousness (50%), papilledema (18%), cranial nerve palsy (33%), hemiparesis (29%), and hypotonia (22%). Predisposing factors were identified in 63 (90%) patients. These included infection (40%), perinatal complications (25%), hypercoagulable/hematological diseases (13%), and various other conditions (10%). Hemorrhagic infarcts occurred in 40% of the patients and hydrocephalus in 10%. Transverse sinus thrombosis was more common (73%) than sagittal sinus thrombosis (35%). Three children underwent thrombolysis, 15 patients received anticoagulation, and 49 (70%) were treated with antibiotics and hydration. Nine (13%) patients (6 of them neonates) died. Twenty-nine patients (41%) were normal, whereas 32 patients (46%) had a neurological deficit at discharge. Seizures and coma at presentation were poor prognostic indicators. In conclusion, cerebral venous thrombosis predominantly affects children younger than age 6 months. Mortality is high (25%) in neonatal cerebral venous thrombosis. Only 18 (25%) patients were treated with anticoagulation or thrombolysis.

Cerebral venous thrombosis: analysis of a multicenter cohort from the United States.

OBJECTIVE: The data regarding diagnosis, prognosis, management, and outcome of patients with cerebral venous thrombosis are limited from the United States. METHODS: Patients with diagnosis of cerebral venous thrombosis were identified by International Classification of Diseases, Ninth Revision coding system at 10 centers in the United States during a 10-year period by retrospective chart review (1991-1997) or prospective enrollment (1997-2001). In all, 232 patients were screened for study inclusion and 182 of these patients were included in the study. RESULTS: The age range was 13 to 82 years (mean 38 years). Hypercoagulable state was the most common predisposing factor followed by pregnancy, malignancy, and homocystinemia. Neurologic examination revealed normal findings in 69 patients (38%); 37 (20%) were comatose, 59 (32%) had papilledema, and 71 (39%) had hemiparesis. In all, 61 patients (33%) had evidence of hemorrhage by computed tomography/magnetic resonance imaging. A total of 27 patients (15%) were treated with thrombolysis and 124 (68%) with anticoagulation. Overall mortality was 13% (n = 24). One-year follow up was available for 96 patients (53%). Of these, 26 (27%) were healthy, 43 (45%) were ambulatory with assistance, and 27 (28%) were still bedridden. On multivariate analysis, the best predictors of a poor outcome were coma at presentation (odds ratio 15.2 [95% confidence interval; 1.5-66]) and intracerebral hemorrhage (odds ratio 8.7 [95% confidence interval; 1.3-34.5]). CONCLUSION: Clinical and radiologic presentation of cerebral venous thrombosis in the United States is not much different from other parts of world but spectrum and frequency of predisposing factors are different. Number of patients treated with thrombolysis is higher as compared with other reported series of such patients. Coma at presentation and intracerebral hemorrhage were the strongest predictors of poor outcome, which is comparable with other series.

Association of Neutrophil/Lymphocyte Ratio With Intravenous Immunoglobulin Treatment in Children With Guillain-Barré Syndrome.

Guillain-Barré syndrome (GBS) is an acute immune-mediated inflammatory polyneuropathy of the peripheral nervous system. The authors aimed to investigate whether the neutrophil/lymphocyte (N/L) and platelet/lymphocyte (P/L) ratios are the parameters that associated with the drug treatment or severity of GBS. Twenty-seven children with GBS were retrospectively analyzed from the medical records of patients who attended to the Pediatric Neurology Department of the Gaziantep University Hospital. Biochemical and hematologic parameters were measured. Leukocytes, neutrophils counts and N/L ratio were significantly higher before the intravenous immunoglobulin treatment ( P < .001). However, there were no marked differences in platelet count and P/L ratio. In addition, marked correlation was observed between the N/L ratio after treatment and duration of weakness. The results of the study showed that N/L ratio is significantly higher in GBS patients, and reduces following with intravenous immunoglobulin treatment.

Efficacy of stem cell therapy in ambulatory and nonambulatory children with Duchenne muscular dystrophy - Phase I-II.

PURPOSE: Duchenne muscular dystrophy (DMD) is an X-linked recessive pediatric disorder that ultimately leads to progressive muscle degeneration. It has been known that cell-based therapies were used to promote muscle regeneration. The main purpose of this study was to investigate the effects of allogeneic Wharton jelly-derived mesenchymal stem cells therapy in Duchenne muscular dystrophy. PATIENTS AND METHODS: Four ambulatory and five nonambulatory male patients were assessed as having acceptance criteria. Gene expression and immunohistochemical analysis were performed for dystrophin gene expression. The fluorescent in situ hybridization method was used for detection of chimerism and donor-recipient compatibility. Complement dependent lymphocytotoxic crossmatch test and detection of panel reactive antigen were performed. All patients were treated with 2 × 106 cells/kg dose of allogeneic Wharton jelly-derived mesenchymal stem cells via intra-arterial and intramuscular administration. Stability was maintained in patient follow-up tests, which are respiratory capacity tests, cardiac measurements, and muscle strength tests. RESULTS: The vastus intermedius muscle was observed in one patient with MRI. Chimerism was detected by fluorescent in situ hybridization and mean gene expression was increased to 3.3-fold. An increase in muscle strength measurements and pulmonary function tests was detected. Additionally, we observed two of nine patients with positive panel reactive antigen result. CONCLUSION: All our procedures are well tolerated, and we have not seen any application-related complications so far. Our main purpose of this study was to investigate the effects of allogeneic mesenchymal stem cell therapy and determine its suitability and safety as a form of treatment in this untreatable disorder.

Idiopathic epilepsy of childhood and potassium ion channels.

The etiology of common idiopathic epileptic syndromes is genetically determined, but the complex pattern of inheritance suggests an epistatic interaction of several susceptibility genes. Mutations in over 70 genes now define biological pathways leading to rare monogenic forms of epilepsy in humans and animals. Recognizing the molecular basis of an ion-channel disease has provided new opportunities for screening, early diagnosis, and therapy of these conditions. Potassium can affect the development of common seizure type and can be defined seizure susceptibility allele. The existence of inward-rectifying potassium (Kir) channels was first recognized half a century ago. The biophysical fingerprint of Kir channels is inward rectification in the current-voltage relationship , which limits potassium efflux at depolarizing membrane potentials. Kir channels are essential in the control of resting membrane potential, coupling of the metabolic cellular state with membrane excitability, and maintenance of potassium homeostasis. The critical interval contains several candidate genes, one of which, KCNJ1O, exhibits a potentially important polymorphism with regard to fundamental aspects of seizure susceptibility. Deletion of KCNJ1O as a seizure susceptibility gene that code for inward rectifier potassium ion channels imparts protection against seizures results in spontaneous seizures and increased seizure susceptibility. The unique role of Kir channels in membrane physiology coupled with previous strong association between ion channel gene mutations and seizure phenotypes puts even greater focus on KCNJ1O. The major challenge of the future will be to recognize the molecular basis of a Kir-mediated channelopathy in order to screen, diagnose and treat these ion channel diseases.

Acute stroke secondary to internal carotid artery pseudoaneurysm: MRI findings and treatment with endovascular coiling.

Internal carotid artery pseudoaneurysms are uncommon. We report a young man with history of trivial trauma who presented with middle cerebral artery stroke. Head CT scan revealed a right parapharyngeal mass. MRI confirmed the diagnosis of internal carotid pseudoaneurysm. Cerebral angiogram showed dissection of internal carotid artery with a large pseudoaneurysm and almost complete occlusion of vessel distal to aneurysm. Vessel was obliterated by fibercoiling and gluing by endovascular technique to diminish risk of further embolization. MRI characteristics of carotid pseudoaneurysms and role of endovascular treatment are discussed.

Brain MRI findings in infants with primary congenital glaucoma.

BACKGROUND: Congenital glaucoma appears in the first months of life, eventually at birth. Isolated congenital glaucoma is characterized by minor malformations of the irido-corneal angle of the anterior chamber of the eye. Clinical manifestations include tearing, photophobia and enlargement of the globe appearing in the first months of life. Imaging technology such as optical coherence tomography and measurement of central corneal thickness may play an important role in the assessment of children with suspected or known glaucoma. However, no MRI findings of the CNS in patients with primary congenital glaucoma (PCG) were reported in the literature. The purpose of this study was to investigate MRI findings of the brain in infants with PCG. METHODS: We reviewed the radiological, histopathological and clinical characteristics of infants with primary congenital glaucoma. The records of 17 patients with PCG were reviewed and the MRIs of the brain and associated manifestations were analyzed. RESULTS: Three patients with PCG had abnormal MRI findings suggesting agenesis of the corpus callosum. Two infants had delayed myelinization of the brain. DISCUSSION: Significant abnormal optic nerve excavation and increased corneal diameters in 2 patients with delayed myelinization may suggest that intraocular pressure can be more striking and more severe, revealing a close relationship with PCG and abnormal myelinization in the white matter. Studies with more patients are needed to confirm these results.

Serial Casting as an Adjunct to Botulinum Toxin Type A Treatment in Children With Cerebral Palsy and Spastic Paraparesis With Scissoring of the Lower Extremities.

The purpose of this study was to examine whether combination therapy of serial casting and botulinum toxin type A injection can further enhance the effects of botulinum toxin type A in children with cerebral palsy with scissoring of both legs. This study was a prospective and randomized trial. The children were divided into 2 groups, one of which received serial casting after botulinum toxin type A (n = 40), and the other which only received botulinum toxin type A (n = 40). Serial casting started 3 weeks after the botulinum toxin type A. Both groups received physiotherapy. Groups were assessed at baseline then compared at 6 and 12 weeks following the intervention. Significant improvements in Gross Motor Function Measure-66 and Caregiver Health Questionnaire were recorded in both groups ( P < .001). The modified Ashworth scale improved significantly following botulinum toxin type A in the serial casting group ( P < .05), but not in botulinum toxin type A only group. These results suggest that serial casting after botulinum toxin type A can enhance the benefits of botulinum toxin type A in children with cerebral palsy.

Paediatric cerebral venous thrombosis.

Cerebral venous thrombosis (CVT) in children is a multifactorial serious disease. It is being increasingly diagnosed, mainly because of more sensitive diagnostic procedures and increasing clinical awareness. The clinical manifestations can be life-threatening and cause long-term neurological deficits. Thromboembolism in children is a multifactorial disorder in which both genetic and acquired risk factors play a role. CVT occurs in various clinical settings, including infection, dehydration, renal failure, trauma, cancer and haematological disorder with multiple risk factors. Clinical manifestations of CSVT are nonspecific and may be subtle. Most of the clinical scenarios occur at all ages and the clinician should consider this diagnosis in a wide range of acute neurological presentations in childhood. CVT can have an extremely variable clinical presentation, mode of onset, imaging appearance and outcome. Its prognosis remains largely unpredictable. Diffusion and perfusion MRI may play a role in detecting venous congestion and CT or MR venography are now the methods of choice for investigation of cerebral venous thrombosis. The options for treatment of infants and children include standard or low molecular weight heparin for 7-10 days followed by oral anticoagulants for 3-6 months. Specific treatment with anticoagulation is controversial in children, but has been established as appropriate therapy in adults. Anticoagulant treatment with heparin is probably safe and beneficial for children with sinus thrombosis, even those with intracranial haemorrhages.

Wernekink comissure syndrome: a rare midbrain syndrome secondary to stroke.

Wernekink commissure involves the decussation of superior cerebellar peduncle (SCP) in midbrain. We report an elderly hypertensive, diabetic man who developed slurred speech, ataxia, and internuclear ophthalmoplegia. MRI examination revealed an unusual ischemic stroke involving Wernekink commissure. This rare stroke pattern involving decussation of SCP occurs in the setting of small arterial disease. The association between the anatomic location of the stroke and clinical findings is noteworthy.

Local thrombolytic treatment of cerebral venous thrombosis in three paediatric patients.

There is increasing evidence that local thrombolysis can be used with relative safety and efficacy in adults with superior sagittal sinus thrombosis (SSST). However, little data is available on the use of local thrombolysis in children with SSST. We report three patients who received local thrombolysis for dural sinus thrombosis. Two patients received urokinase and one patient received urokinase followed by local TPA infusion. Recanalization was achieved in two patients.

The Clinical Implications of Todd Paralysis in Children With Benign Rolandic Epilepsy.

The aim of this study was to describe the clinical and electroencephalographic (EEG) findings of postictal Todd paralysis in benign rolandic epilepsy of childhood and find out the possible correlation with migraine. Based on International Headache Society pediatric migraine criteria, patients were investigated for migraine, and 12 of the 108 patients with benign rolandic epilepsy (6 girls and 6 boys, 11.1%) were found to have postictal Todd paralysis. Ten of these 12 patients (83.3%) had pediatric migraine based on the diagnostic criteria. We showed comorbidity of migraine and benign rolandic epilepsy with postictal Todd paralysis in children. Increased incidence of migraine in the present study suggest that children who have benign rolandic epilepsy and postictal Todd paralysis are more likely to have migraines.