Relationship between heroin spongiform leucoencephalopathy and respiratory chain complex I deficiency / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the relationship between heroin spongiform leucoencephalopathy and respiratory chain complex I deficiency.</p><p><b>METHODS</b>The activity of respiratory chain complex I in peripheral white blood cell mitochondria was compared between 36 cases of heroin spongiform leucoencephalopathy and 36 healthy subjects using enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>The activity of respiratory chain complex I was 5.6∓2.4 U/ml in patients with heroin spongiform leucoencephalopathy, significantly higher than that in the normal subjects (4.2∓2.1 U/ml, t=2.634, P<0.05).</p><p><b>CONCLUSION</b>In patients with heroin spongiform leucoencephalopathy, mitochondrial dysfunction results in energy metabolism disorder to cause extensive demyelination of the cerebral white matter. Respiratory chain complex I deficiency of the mitochondria plays a significant role in the pathogenesis of heroin spongiform leucoencephalopathy.</p>

Clinical Manifestations of Leukodystrophies: A Single Center Study / 대한소아신경학회지

PURPOSE: Leukodystrophies have been defined as inherited metabolic disorders of myelin resulting in abnormal development or progressive destruction of the white matter. This study was performed to investigate the clinical manifestations and treatments of leukodystrophies in a single Korean tertiary center. METHODS: We retrospectively analysed the medical records of patients who had been diagnosed with leukodystrophy from May 1995 to May 2010 at the Asan Medical Center. RESULTS: During the 15-year study period, 36 cases of leukodystrophies were diagnosed with an verage age at symptom presentation of 49 months. Prominent symptoms at presentation were developmental delay (41%) and seizure (25%); however, nystagmus, developmental regression, hearing loss, gait disturbance, visual disturbance, attention deficit, hypotonia, hyperpigmentation, and hemiparesis were also observed. On MRI, periventricular involvement was noted frequently. The most common diagnoses were adrenoleukodystophy (25%), metachromatic leukodystrophy (11%), Krabbe disease (11%), and Pelizaeus-Merzbacher disease (8.3%). No final diagnosis was made in 14 cases (41%). Bone marrow transplantation was performed in 4 patients and showed favorable prognoses. CONCLUSION: Clinical features of leukodystrophies are not specific to diagnosis and most leukodystrophies remain undiagnosed; however, a logical algorithm based on prevalence could aid the laboratory testing. Because early detection and diagnosis is crucial for treatment and prognosis, it is important to have a high index of suspicion and watchful screening of familial history.

Association of cytochrome P4502D6 gene polymorphism with the susceptibility of heroin spongiform leucoencephalopathy / 南方医科大学学报

<p><b>OBJECTIVE</b>To elucidate the relation between cytochrome P4502D6 (CYP2D6) gene polymorphism and the susceptibility of heroin spongiform leucoencephalopathy (HSLE).</p><p><b>METHODS</b>With polymerase chain reaction-restriction fragment length polymorphism technique, the cytochrome P4502D6 gene polymorphisms were analyzed in HSLE cases and control subjects.</p><p><b>RESULTS</b>The frequencies of CYP2D6 (CYP2D6/C188, CYP2D6/L2938, CYP2D6/G4268) gene mutations were higher in HSLE patients than in the controls.</p><p><b>CONCLUSION</b>The CYP2D6 gene mutation is associated with a high risk of HSLE.</p>

Pathological analysis of heroin spongiform leukoencephalopathy / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the pathological characteristics of heroin spongiform leukoencephalopathy (HSLE).</p><p><b>METHODS</b>Cerebral tissue specimens were obtained from 15 patients with HSLE and the histological observations under optical and electron microscopes were carried out by HE, Bielschowsky's, and chromotrope 2R-brilliant green staining.</p><p><b>RESULTS</b>HSLE was characterized primarily by spongiform vacuolar degeneration of the cerebral white matter. Neurons in the gray matter, Purkinje and granular cells in the cerebella remain intact in all the cases. Numerous vacuoles, which merged to form larger cavities, appeared in the damaged white matter, and the axons survived in the deep white matter. The myelin sheath in the cerebellar white matter sustained more severe damages than those in the cerebral white matter. No vacuoles or lymphocyte infiltration occurred in the small peripheral vessels.</p><p><b>CONCLUSION</b>HSLE is pathologically characterized by vacuolar degeneration due to primary damage of the myelin, and the spongiform vacuolar degeneration is closely associated with the severity of demyelination in the white matter.</p>

Leukodystrophies: Indian scenario.

The leukodystrophies are familial disorders with onset usually in infancy or childhood. The clinical features consist of motor dysfunction with varying degree of cognitive decline. Magnetic Resonance Imaging (MRI) has helped to identify and characterize these disorders. In some leukodystrophies, biochemical enzymatic and genetic defects have been identified. The commonest leukodystrophy seen in India is Megalencephalic Leukodystrophy with subcortical cysts. The essential features consist of large head, mild pyramidal and cerebellar dysfunction, and occasional seizures. MRI studies show extensive white matter changes with temporal cysts. It is common in the Agarwal community in India. An identical mutation in exon 2 of the MLC 1 gene has been identified in this community suggesting a founder effect.

A Case of Canavan Disease

Canavan disease, also known as van Bogaert-Bertrand disease, is a rare autosomal recessive disorder characterized by early an onset and a progressive spongyform degeneration of the brain, associated with an edema of the central nerve system, intramyelinic swelling and neurologic symptoms. This disorder is most prevalent in people of Ashkenazi Jewish descent but has been observed in other ethnic groups. Patients have severe mental retardation, poor head control, macrocephaly and seizures. Canavan disease is caused by the accumulation of N-acetylaspartic acid(NAA) in the brain as the result of a deficiency of aspartoacylase(ASPA) activity. Most children are reported to have the infantile form, becoming symptomatic between three and six month of age, after unremarkable prenatal and perinatal course. We experienced a case of Canavan disease in a six day old female newborn baby, associated with seizure, degeneration of brain white matter and markedly elevated urine N-acetylaspartic acid(NAA) level. So, we report the case with a brief review of the related literature.

A Case of Canavan Disease / 대한소아신경학회지

Canavan disease(CD) is a rare autosomal recessive leukodystrophy caused by the deficiency of aspartoacylase and the accumulation in brain of N-acetylaspartate(NAA). CD has been reported mainly Ashkenazi Jews but also occurs in other ethnic groups. Usually it presents as early as the third month of life with megalencephaly, hypotonia later progressing to hypertonia, psychomotor and mental retardation, blindness, occasionally deafness and seizure. Diagnosis is based on the clinical feature, N-acetylaspartic aciduria, radiologic and pathologic findings. Histologically, the affected white matter shows extensive vacuolation and demyelination. There is no treatment for CD and the only prevention is through genetic counselling and prenatal diagnosis. We experienced a case of Canavan disease that was presented with hypotonia and developmental delay. Diagnosis was confirmed histologically. Radiologic findings are extensive high signal throughout the white matter on T2-weighted MRI and increased NAA peak and decreased choline peak of the white matter on MR spectroscopy.

Neonatal listeriosis

A total of one hundred and fifty newborns were studied: 30 with a picture of septicemia. 30 preterm, 30 with hyper bilirubinemia, 40 with respiratory distress and twenty healthy full term newborns as a control group. The work included cord and neonatal blood cultures and subcultures on blood agar and Listeria selective medias, transillumination technique, biochemical reactions for differentiation of different organisms in addition to detection of Listeria immunoglobulins against [la] and [4b]. The 150 cord blood cultures revealed: 127/150 [84.66 percent] were negative, 23/150 [15.33 percent] were infected with Staph [4 percent], Strep [5.33 percent], E.coli [4 percent] and Listeria 3/150 [2 percent]. The 150 neonatal blood cultures revealed: 60/150 [40 percent] were negative, 90/150 [60 percent] were infected with: Staph [20 percent], Strept [17.33 percent], E coli [12.66 percent], Listeria 7/150 [4.66 percent], Pseudomonas [4.66 percent] and Pneumococci [0.66 percent]. The 7 cases of neonatal listeriosis were distributed as follows 4/7 [57.1 percent] in septic group, 2/7 [28.6 percent] in Respiratory distress group, 1/7 [14.3 percent] in hyperbilirubinmic group. The most common clinical presentations were poor suckling [85.7 percent], Lethargy [85.7 percent], hypothermia [57.14 percent], vomiting [42.8 percent], cyanosis [42.8 percent] and granulomas of mucous membrane [28.5 percent]. The Listeria positive cases revealed a significant decrease in weight 3.11+1.73, [P<0.05] and midarm circumference 11.54+0.89 [P< 0.05] but no statistically significant change in length and head circumference when compared to the full term healthy newborns. Inspite of immediate initiation of specific antibiotics combination the mortality rate was 2/7 [28.57 percent]. Three cases [42.8 percent] with high antibody titer against Listeria [4b] were positive to Listeria in both cord and neonatal blood cultures, the other 4/7 [57.1 percent] with also high antibody titer, were positive only in neonatal blood culture. The perinatal Listeriosis can occur through the contaminated hands of the personnel or by contaminated equipment used in handling babies and their mothers