Developmental abnormalities of mid and hindbrain: a study of 23 Egyptian patients

With the advent of neuroimaging modalities specifically, magnetic resonance imaging [MRI], recognition of developmental defects of posterior fossa has greatly improved. Is to delineate the clinical, cytogenetics and radiological features of patients with midhindbrain anomalies. Twenty-three patients with mid-hind brain malformations were included in this study. Complete clinical evaluation, cytogenetic analysis and neuroradiological study were done for each patient. Patients' sex ratio was [M: F/ 0.9:1] and the mean age was 2.17 years. Parental consanguinity was 86.9% and positive family history was recorded in 7 families. Based on clinico-radiological findings, patients were categorized as Joubert syndrome and related cerebellar disorders [34.8%], pontocerebellar hypoplasia [26.1%], lissencephaly cerebellar hypoplasia [13%], isolated cobblestone lissencephaly with normal muscle and eye [8.7%], isolated vermian hypoplasia [13%] and retrocerebellar cyst [4.4%]. Cytogenetic analysis revealed abnormalities in 3 patients [13%]; pericentric inversion of chromosome 8 in a patient with lissencephaly cerebellar hypoplasia, del 5p14.3-pter delineating Cri du chat syndrome and associated with vermian hypoplasia and del 18q21.1-qter in a patient with retrocerebellar cyst due to paternal balanced translocation t [4;18]. FISH for specific locus and whole chromosomal painting were used to document the assigned aberrations. Although most of the cerebellar malformations are of Mendelian inheritance, this study emphasizes the importance of chromosomal analysis for patients with posterior fossa anomalies. With more researches describing clinico-radiological characterization of hind brain dysgenesis will allow better understanding of these disorders, further delineation of relevant syndromes and new genes identification

Study of neurometabolic disorders in Egyptian children

Background: Metabolic brain diseases usually present with a complex neurological picture so they are often overlooked. This prospective study was undertaken to focus on the clinical aspects, biochemical abnormalities and neuroimaging of the brain in children suffering from neurometabolic disorders

Patients and methods: This study was carried out on 130 patients suspected clinically of having metabolic brain diseases and presented to the neuropediatric clinic, neonatal intensive care unit in Benha faculty of medicine and the neurometabolic specialized clinic in Abu El-Reesh hospital. The diagnosis of neurometabolic disorders was confirmed in 29 children [22%]. They were 19 males and 10 females, their age ranged from 5 days to 10 yrs with mean age 3.61 +/- 2.2 years. They presented with clinical manifestations suggestive of metabolic brain diseases. They were subjected to thorough history, clinical examination, investigations in the form of serum ammonia, serum lactate ,blood glucose, blood gases assessment, ketone bodies in urine, CPK [creatine phosphokinase],urine organic acids, plasma aminogram, enzymatic assay, EMG [Electromyography],EEG[electroencephalography], muscle biopsy, CT and MRI of the brain

Results: Patients were classified according to their clinical presentations, biochemical and radiological findings into 5 groups, Group I, Organic acidemia 10 cases [34.5%], including, Methyl malonic acidemia [4 cases], Biotinidase deficiency [3 cases], Glutaric Aciduria type 1 [2 cases] and Maple syrup urine disease [one case]. Group II, Mitochondrial disorders 9 cases [31%] including, Leigh syndrome [4 cases], Pyruvate dehydrogenase deficiency [2 cases], mitochondrial encephalomyopathy [2 cases] and MELAS syndrome[mitochondrial encephalopathy, lactic acidosis and stroke] [one case]. Group III, Urea cycle abnormalities 5 cases [17.2 %]. Group IV Aminoacidopathy 3 cases [10.4 %]in the form of Phenylketonuria. Group V Fatty acid oxidation defect 2 cases [6.9%]. The main neurological manifestations were global developmental delay [93.1%], seizures [89.7%], hypertonia [65.5%] and microcephaly [55.2%]. Biochemical abnormalities were: Group I: had acidosis in 9 cases[90%] [ketoacidosis in [4 cases],lactic acidosis in[3 cases],acidosis without ketosis in [2 cases]], ketosis only in one case [10%] and hyperammonemia in 7 cases [70%] of cases. GroupII: had mainly lactic acidosis 5 cases [55.6%] and mild hyperammonemia [11.1%]. GroupIII: had isolated hyperammonemia [100%]. Group IV: had hyperphenylalaninemia in [100%] of cases with phenylketonuria. Group V: had lactic acidosis,mild hyperammonemia, hypoglycemia and absent ketosis in [100%]of cases. Neuroimaging showed abnormal findings in the form of basal ganglia abnormalities [41.4%], brain atrophy [27.5%], diffuse demeylination and focal demeylination [6.9%]each and normal findings in [17.3%]

Conclusion: Presence of unexplained neurological symptoms whose severity is out of proportion to the inciting illness should arouse suspicion of a metabolic disease. Screening tests like blood gas analysis, blood levels of lactate, glucose and ammonia, urine examination for ketones and neuroimaging provide valuable clues to the presence of an underlying metabolic disease

Application of polymerase chain reaction to the diagnosis of congenital toxoplasma and herpes simplex virus infection

Because Polymerase Chain Reaction [PCR] is a sensitive, rapid and specific method, we applied it on the sera and CSF of 42 patients in whom congenital toxoplasmosis or herpes simplex virus infection were suspected clinically seeking for a rapid and better diagnostic approach for these treatable congenital infections in order to minimize their morbidity and mortality by early therapeutic intervention . PCR was also applied on the sera of 12 mothers, the CSF and sera of 10 controls. HSV1 IGM antibody was performed by enzyme linked immunoassay [EIA] on all samples. HSVDNA was detected successfully by PCR in serum and CSF samples of 32/42 patients [16/21 neonates, 76.2% ; 16/21 infants 76.2%] and in the sera of 9/12 mothers, while HSV[1] IGM antibodies were positive in 21/42 cases, 50% [9/21 neonates, 42.8% ; 11/21 infants 52.3%] with a sensitivity of 70.8% and 41.2% for serum and CSF respectively while specificity was 100% for both samples [PCR isa golden standard method 100%]. PCR proved to be superior to serology detecting 11 additional cases with congenital HSV infection. SO, PCR. could be usefull for the confirmative diagnosis of congenital HSV infection especially in serologically negative cases. Concerning toxoplasmosis, the system adopted in this study using the P30 gene failed to detect toxoplasma DNA in the serum and CSF samples of ail studied cases. Therefore, for adequate laboratory diagnosis of toxoplasmosis, combination of several different test systems including immunoblot technique in addition to PCR and usage of at least 2 different toxoplasma gondii strains as antigens is mandatory