Treatment challenges in pediatric stroke patients.

Aim. In this study we presented our experience of 18 years on the etiology, risk factors, prophylactic and acute treatment, the effect of treatment to recurrence rate of patients with stroke. Methods. The population included 108 patients who had been treated for stroke at Pediatric Neurology Department of Ankara University with the diagnosis of arterial ischemic stroke and sinovenous thrombosis between January 1992 and August 2010. Forty-one girls (38%) and 67 boys (62%) with mean symptom age 3.1 ± 4.04 years, (0-18 years old) were followed up with a mean period of 4.9 ± 3.78 years (0-17 years). Results. 30 patients had no risk factors, 34 patients had only one risk factor and 44 patients had multiple risk factors. Recurrence was seen in three patients. There was no any statistical correlation between the recurrence of stroke and the existence of risk factors (P = .961). Seventeen patients received prophylactic treatment; 2 of them without any risk factors, 3 had one risk factor, 12 patients, who constituted the majority of our patients, had multiple risk factors (P = .024). Conclusion. With this study we showed that the right prophylaxis for right patients reduces the rate of recurrence.

Distal truncation of KCC3 in non-French Canadian HMSN/ACC families.

BACKGROUND: Hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC) is a severe and progressive autosomal recessive polyneuropathy. Mutations in the potassium-chloride cotransporter 3 gene (KCC3) were identified as responsible for HMSN/ACC in the French Canadian (FC) population. In the present study, the authors were interested in finding new mutations in non-FC populations, assessing the activity of mutant proteins and refining genotype-phenotype correlations. METHODS: The authors screened KCC3 for mutations using direct sequencing in six non-FC HMSN/ACC families. They then assessed the functionality of the most common mutant protein using a flux assay in Xenopus laevis oocytes. RESULTS: The authors identified mutations in exon 22 of KCC3: a novel mutation (del + 2994-3003; E1015X) in one family, as well as a known mutation (3031C-->T; R1011X) found in five unrelated families and associated with two different haplotypes. The function of the cotransporter was abolished, although a limited amount of mutant proteins were correctly localized at the membrane. CONCLUSIONS: KCC3 mutations in exon 22 constitute a recurrent mutation site for hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC), regardless of ethnic origin, and are the most common cause of HMSN/ACC in the non-French Canadian (FC) families analyzed so far. Therefore, for genetic analysis, exon 22 screening should be prioritized in non-FC populations. Finally, the R1011X mutation leads to the abrogation of KCC3's function in Xenopus laevis oocytes, likely due to impaired transit of the cotransporter.

Toxic hepatitis in a case of Angelman syndrome associated with Lennox-Gastaut syndrome.

We report a 26-month-old boy with Angelman syndrome associated with Lennox-Gastaut syndrome, who developed a rash and a persistent toxic hepatitis after lamotrigine was added to valproate therapy. The patient had typical findings of both Angelman and Lennox-Gastaut syndromes. Chromosome analysis performing by FISH analysis showed a deletion in chromosome 15 (q11.2 q11.2). Although some cases of Angelman syndrome associated with Lennox-Gastaut syndrome were reported in the literature, valproate and/or lamotrigine induced toxic hepatitis in Angelman syndrome has hitherto never been described. We conclude that VPA and LTG combination should be given with great caution or avoided in patients with Angelman syndrome.

Psychotic disorder in a case with Hallervorden-Spatz disease.

OBJECTIVE: Hallervorden-Spatz disease is a rare autosomal recessive condition, with early onset of predominantly extrapyramidal dysfunction. The symptoms of the disease are dystonia, rigidity, choreoathetosis, pyramidal signs, and intellectual decline. Recent genetic studies mapped the disease to chromosome 20p12.3-p13, and identified mutations in the pantothenate kinase gene. This report describes a childhood onset case of Hallervorden-Spatz disease with schizophreniform psychotic symptoms. Former reports about the psychiatric comorbidity generally included depressive disorder. METHOD: A single case report. RESULTS: A 14-year-old boy with Hallervorden-Spatz disease presented a psychotic episode with prominent auditory hallucinations. Symptoms were relieved after neuroleptic treatment. CONCLUSION: To the authors' knowledge, this is the first published report of the disease with psychotic symptoms. The contribution of basal ganglia, with their wide projections, to the emergence of psychotic symptoms was discussed.

Do we consider Andermann syndrome in infants with agenesis of corpus callosum.

Andermann syndrome is characterized by agenesis of corpus callosum, anterior horn cell disease, a mixed sensory and motor neuropathy, and facial dysmorphism, and is inherited as an autosomal recessive trait. A 7-month-old boy was admitted with developmental retardation. Head control was not gained and he could not sit. He had high arched palate, elongated facies and large angle of the mandible, which were compatible with the Andermann syndrome. Moderate hypotonicity and absent tendon reflexes were also noted. Serum creatine kinase level was normal. Magnetic resonance imaging of the brain showed agenesis of the corpus callosum. Electromyographic examination revealed the presence of both sensory and motor neuropathy. The patient was diagnosed as having the Andermann syndrome according to the clinical and laboratory findings and he is reported due to rare presentation.

A fatal case of cerebellar hypoplasia associated with anterior horn cell disease.

A 27-month-old girl was admitted with inability to walk and speak. The pregnancy, labor and delivery were unremarkable. She was the second child of first degree consanguineous parents and the other 5-year-old child was healthy. On physical examination, she could sit without aid. Horizontal nystagmus and bilateral optic atrophy were diagnosed. Moderate hypotonicity and muscle atrophy were noted in the lower extremities, and deep tendon reflexes were found to be brisk. Serum creatine kinase level was normal. Brainstem auditory evoked potential was also bilateral normal. Flash visual evoked potential was found to be prolonged bilaterally. Magnetic resonance imaging of the brain showed severe cerebellar hypoplasia and mild cerebral atrophy. Electromyographic examination was consistent with anterior horn cell disease. Muscle biopsy specimen was unremarkable. Genetic analysis was unremarkable. The patient was diagnosed with cerebellar hypoplasia associated with anterior horn cell disease, which was named as amyotrophic cerebellar hypoplasia, Norman's disease or infantile neuronal degeneration in the literature. During the follow-up, the parents said that she died at the age of 34 months, because of probable infection.

Atypical benign partial epilepsy of childhood (pseudo-Lennox syndrome): report of two brothers.

Two brothers (3 and 2 year old) with characteristic findings of atypical benign partial epilepsy of childhood (pseudo-Lennox syndrome) are reported, to emphasize the presence of a possibility of a genetic basis of this disorder and the importance of intravenous immune globulin (IVIG), vigabatrin (VGB) and lamotrigine (LTG) therapy. Sleep EEGs of both the patients showed typical features of Lennox-Gastaut syndrome. On follow-up, the convulsions were found to be resistant to numerous antiepileptic agents in one patient while they were easily controlled with LTG monotherapy in the other patient. In the elder brother, who was diagnosed as intractable epilepsy, the convulsions disappeared with IVIG and VGB. During the long term follow-up, they were seizure free for five and two years respectively, and their mental motor development was excellent.

Hypopotassemic paralysis: a rare presentation of proximal renal tubular acidosis.

Neurologic manifestations can accompany systemic diseases, and primary disease can be identified with a careful history, physical examination, and laboratory investigations. A 14-year-old girl with paraplegia and absence of deep tendon reflexes in the lower extremities after 2 days of vomiting and diarrhea was referred to our pediatric neurology department with a diagnosis of Guillain-Barré syndrome. Short stature, dehydration, motor and mental retardation, bilateral cataracts, glaucoma, and band keratopathy were detected on physical examination. Hypopotassemia and severe metabolic acidosis were found on biochemical examination. Her paraplegia improved after appropriate fluid and electrolyte replacement, but metabolic acidosis persisted after cessation of intravenous therapy, and isolated proximal renal tubular acidosis was detected. Because she had isolated proximal renal tubular acidosis and other abnormalities, she was diagnosed with Donckerwolcke-Winsnes syndrome.

Masturbation mimicking seizure in an infant.

A 3.5-month-old boy was referred to our hospital with the diagnosis of infantile spasm. His developmental milestones and physical examination were normal. During the follow-up we recorded about six to nine attacks a day and the duration of attacks was changed between 15 seconds-1.5 minutes. During the episodic attacks he was flushed and had tonic posturing associated with crossing of thighs, without loss of consciousness and his eye movements were normal. Routine and long-term electroencephalogram (EEG) were normal during attack. The patient was diagnosed as masturbation according to the clinical and EEG findings. In conclusion, we would like to stress that masturbation should also be considered in infants who were admitted with complaint of seizure, and aside from EEG monitoring a detailed history and careful observation are very important factors in differential diagnosis of these two different conditions.

Encephalocraniocutaneous lipomatosis associated with iris coloboma, chorioretinitis and spinal cord involvement: a case report.

A 9-year-old boy with a history of lipoma excision and laminectomy at the Th10-11 levels, resulting in incomplete paraparesis and neurogenic bladder, was admitted for a comprehensive rehabilitation programme. Physical examination revealed an ipsilateral focal dermal hypoplastic defect within an area of alopecia and a subcutaneous lipomatous tissue on the left temporo-parietal region of the scalp. Iris coloboma and chorioretinitis were diagnosed on the left eye. He also had mild mental retardation and triparesis. Magnetic resonance imaging of the brain and the spine demonstrated hyperintense masses which were consistent with lipoma. Although in the literature three cases of encephalocraniocutaneous lipomatosis (ECCL) concomitant with spinal cord involvement have been reported, to our knowledge iris coloboma and chorioretinitis in ECCL have not been reported previously. In conclusion, we would like to stress that aside from known ophthalmological malformations, iris coloboma and chorioretinitis may also be observed in ECCL and that all patients who have been diagnosed as having ECCL should be examined for spinal cord involvement.

Mobius syndrome associated with ventricular septal defect.

We report a 10-year-old boy with Mobius syndrome (MS) associated with ventricular septal defect who was delivered after an unsuccessful curettage before the 10th week of gestation. Methylergobasine which is an ergot alkaloid was also applied during the curettage procedure. Despite of the curettage procedure, the pregnancy was continued and he was delivered. His developmental milestones were delayed. On account of this case, we think that direct mechanical fetal trauma and vasoconstriction or both may cause MS. But, further extensive studies are needed to verify this hypothesis.

The effect of iron supplementation on visual-evoked potentials in infants with iron-deficiency anemia.

Flash visual-evoked potentials were studied in 20 infants with iron-deficiency anemia to determine the effect of iron deficiency on visual function by using visual-evoked potentials in this type of anemia. After iron therapy for 12 weeks, visual-evoked potentials were retested in these otherwise healthy infants. All infants showed an excellent hematological response to iron therapy. Post-treatment visual-evoked potential N2 latencies (negative deflections) decreased significantly compared to the pre-treatment values (p < 0.05). These results suggest that iron-deficiency anemia causes subclinical visual impairment, and visual-evoked potentials may be a useful non-invasive means of detecting subtle effects of nutritional deficiencies and monitoring the nutritional status of infants.

Plasminogen activator inhibitor-1 4G/5G polymorphism in Turkish children with cerebral infarct and effect on factor V 1691 A mutation.

The thrombotic risk of carrying plasminogen activator inhibitor-1-675 4G allele was found to be controversial in previous studies. The aim of this study was to evaluate the possible effect of plasminogen activator inhibitor-1 4G/5G polymorphism in the pathogenesis of childhood stroke. The case-control study included 43 patients with cerebral infarct who were below the age of 18 years (range, 10 months to 18 years) and 113 healthy unrelated individuals without family histories of thrombosis. Plasminogen activator inhibitor-1 4G/5G polymorphism was analyzed according to a previously described method. There was no statistically significant difference in patient and control groups for the distribution of plasminogen activator inhibitor-1 4G/5G polymorphism (P = .75) (allele frequency 4G controls: 0.50; patients: 0.53). However, there was a significant difference for the factor V (FV) 1691 A mutation for both groups (P = .0007).

Common mutations at the homocysteine metabolism pathway and pediatric stroke.

Heterozygosity and/or homozygosity for mutations at the genes of the enzymes involved in homocysteine metabolism may confer an increased risk for thrombosis by causing hyperhomocysteinemia. Although the mutations related to homocysteine metabolism possibly increase the risk of stroke, the data are conflicting and there are very few reports linking these defects to acute stroke in children. We aimed to study the role of these mutations in Turkish children with ischemic stroke. Forty-six patients having cerebral infarct were clinically diagnosed, and the infarction verified with magnetic resonance imaging of the brain was included in the study. All patients were below the age of 18 (10 months to 18 years). Sixty-eight controls, consecutively selected among healthy unrelated subjects from the same geographic area of Turkey without personal and family history of thrombosis, stroke or Behest's disease, were included. Genotyping for the common mutations was carried out by the methods described previously. There was no difference between the pediatric stroke patients and controls for the distribution of methylene tetrahydrofolate reductase (MTHFR) 677 C-T, MTHFR 1298 A-C, methylene tetrahydrofolate dehydrogenase (MTHFD) 1958 G-A and methionine synthase reductase (MTRR) 66 A-G alleles. There was no risk for double gene alterations (MTHFR 677 C-T vs. 1298 A-C) after individuals with FV 1691 A mutation is excluded. Twelve of the 46 patients were found to carry FV 1691 A mutation (26.0%), one being homozygote. The cerebral infarct risk for FV 1691 A was found to be 6.4 (CI 95% 1.7-23.0). Eight of the 46 patients were found to carry PT 20210 A mutation (16.6%). Two of the FV 1691 A heterozygous patients carried PT 20210 A mutation at the same time (4.2%). As a conclusion, we can say that FV 1691 A and PT 20210 A mutations are important and must be included to the routine analysis of pediatric stroke patients.

The alpha2 Gene alleles of the platelet collagen receptor integrin alpha2 beta1 in Turkish children with cerebral infarct.

The possible role of point mutations in the platelet integrin alpha2 beta1 gene in Turkish children with ischemic stroke was evaluated in this study. The case-control study included 44 pediatric patients with cerebral infarct (age range, 10 months to 18 years) and 96 healthy unrelated individuals. Genotyping was performed according to previously described methods. Distribution of the three haplotypes were 36.4%, 45.3%, 10.4% and 31.8%, 50.0%, 13.6% for the controls and the patients, respectively. A new fourth haplotype was found which was 7.8% and 4.5% respectively. Our data indicated that these haplotypes are not risk factors in pediatric stroke group.

Brainstem auditory-evoked potentials in iron-deficiency anemia.

Slight-to-moderate impairments may be observed in mental and motor developments of infants with iron- deficiency anemia. Brainstem auditory-evoked potentials provide a noninvasive means of examining the auditory aspect of the central nervous system functions. In this study the effect of iron-deficiency anemia on auditory functions was investigated by using brainstem auditory-evoked potentials. Brainstem auditory-evoked potentials of the 20 iron-deficient infants were not significantly different from those of the control group that included 20 healthy age-matched infants. Furthermore, there was not a statistically significant difference between the brainstem auditory-evoked potentials of the study group performed before and 3 months after oral iron therapy. Although we could not demonstrate a hearing loss in infants with moderate iron-deficiency anemia in this study, the relationship between severe iron-deficiency anemia and hearing loss or auditory dysfunction remains to be determined.

Cerebral blood flow abnormalities in symptomatic West syndrome: a single photon emission computed tomography study.

BACKGROUND: Infantile spasm (IS) is an age-dependent epileptic encephalopathy of variable etiology. Although IS is well studied, its pathogenesis is unclear. Infantile spasm is usually considered a generalized epilepsy, but recent studies point to focal cerebral blood flow (CBF) abnormalities. METHODS: In six symptomatic IS patients, single photon emission computed tomography (SPECT) with [99Tc]-HMPAO, electroencephalography (EEG), magnetic resonance imaging (MRI)/computed tomography (CT) and their correlation were evaluated. RESULTS: Single photon emission computed tomography showed unifocal (regional) cerebral hypoperfusion in two infants, multifocal (diffuse) cerebral hypoperfusion in three infants and normal perfusion in the other infant. Electroencephalograms obtained in near-time of the SPECT studies showed diffuse abnormalities in five infants with hypoperfusion on SPECT. Cranial MRI/CT showed diffuse and/or localized cerebral lesions in all infants, all of whom had corresponding areas of hypoperfusion on SPECT. In one patient whose spasms were stopped with anticonvulsants, SPECT was normal, in two patients SPECT showed unifocal lesions, while in another three patients whose spasms were decreased but not stopped, SPECT showed multifocal hypoperfusion. CONCLUSIONS: This pilot study may indicate that there are CBF anomalies in symptomatic IS. The degree of CBF may be a predictor of prognosis and multifocal hypoperfusion may be a poor prognostic criteria in IS.

Neurophysiological changes in COPD patients with chronic respiratory insufficiency.

Chronic hypoxemia is known to cause peripheral neuropathy (PNP) in chronic obstructive pulmonary disease (COPD) patients. We aimed to know how often PNP is encountered in such patients and the changes in the central nervous system (CNS) if any. We enrolled 32 patients (30 M, 2 F; mean age +/- SD: 61.5 +/- 8.8 years) with COPD into the study. PaO2 > or = 55 mmHg was considered as the cut-off value designating tissue hypoxia. According to this cut-off value the subjects were divided into two groups: Group I, n: 19, PaO2 < 55 mmHg and Group II, n: 13, PaO2 > or = 55 mmHg. All subjects were evaluated with motor and sensory nerve conduction studies (MNCV and SNCV, respectively), electromyography, visual and brainstem evoked potentials (VER and BAER, respectively). We detected PNP in 93.8% of the study subjects. Distal latency of sural nerve correlated significantly with cigarette consumption and reduction in PEFR. SNCV of median nerve was reduced as PaCO2 was elevated and pH was lowered. BAER wave III latency showed significant inverse correlation with PEFR, FEF25 and FEF25-75. Interpeak latency (IPL) of BAER I-III was also significantly and inversely correlated with FEV1/FVC and FEF25-75. IPL of BAER III-V too showed significant correlations with PaCO2, HCO3- and pH of the arterial blood. As BAER III and IPLs of it represent the pontomedullary portion of the brain, cigarette smoking and airways obstruction may not only cause peripheral neuropathy but also a delay in evoked responses of the brain stem by inducing chronic hypercapnia and respiratory acidosis in patients with COPD.

Factor V (His 1299 Arg) in young Turkish patients with cerebral infarct.

Inherited gene defects related to the coagulation system have been reported as risk factors for stroke. Recently, a genetic component in the factor V (FV) gene that contributes to activated protein C resistance both in the presence and absence of FV 1691 G-->A was reported. This highly conserved FV gene haplotype was marked as R2 polymorphism, an A to G alteration at position 4070 in exon 13 that predicts the His 1299 Arg substitutions. The aim of this study was to evaluate the role of this mutation in Turkish children with ischemic infarct. The case-control study included 48 patients with cerebral infarction; all were 18 years of age or younger (range: 10 months to 18 years). Ten (20.8%) of the 48 patients were found to carry the FV 1299 His-->Arg mutation, one being homozygous. One patient who had a combination of FV 1691 G-->A and protein C deficiency also carried the FV 4070A mutation. A homozygous FV 1299A patient had a prothrombin (PT) 20210A mutation in the heterozygous state. The cerebral infarct risk for FV 1299 was found to be 2.4 (95% confidence interval 0.9-6.8) for all groups. When underlying conditions were excluded, the incidence of FV 1299 was found to be 8/35 (22.8%), but the risk was almost the same. When two other common thrombophilic mutations (i.e. FV 1691 G-->A and PT 20210 G-->A) were excluded, the incidence of FV 4070 mutation increased to 7/21 (33.3%). The risk also increased to 3.9 (95% confidence interval 1.2-12.3).