Outcome of central pontine and extrapontine myelinolysis (n = 44).

The findings in 44 patients (42 of whom were chronic alcoholics) with central pontine myelinolysis show that the outcome does not depend on the severity of neurological deficits during the acute phase of the condition or on concomitant internal diseases, including the degree of hyponatremia. Of the 34 patients for whom follow-up data were available, 32 survived. Of these 11 completely recovered, 11 had some deficits but were independent, and 10 were dependent (4 through disorders of memory or cognition, 3 with tetraparesis, 2 with cerebellar ataxia, 1 with polyneuropathy). The electrophysiological findings did not contribute usefully to the prediction of outcome. Additional neuroradiological diagnostic testing with magnetic resonance imaging was also of no prognostic significance. The extent of the initial pontine lesion was not correlated with the severity of clinical findings during the acute phase of disease, nor was persistence of the pontine lesion as usually seen on magnetic resonance imaging correlated with clinical improvement. We conclude that patients with cerebral myelinolysis survive if the nonspecific secondary complications of transient illnesses such as aspiration pneumonia, ascending urinary tract infection with subsequent septicemia, deep venous thrombosis, and pulmonary embolism can be avoided.

[Does maternal obesity increase the risk of fetal abnormalities? Analysis of 20,248 newborn infants of the Mainz Birth Register for detecting congenital abnormalities]. / Erhöht mütterliche Adipositas das Risiko für kindliche Fehlbildungen? Analyse von 20,248 Neugeborenen des Mainzer Geburtenregisters zur Erfassung angeborener Fehlbildungen.

AIM: To investigate the risk of congenital malformations for newborn of obese women (BMI > or = 30) compared with women of average prepregnancy weight. METHODS: We performed a prospective, population-based case-control study of 20,248 newborn born in the city of Mainz. A total of 1,451 infants (cases) with and 8,088 without congenital malformations (controls) were analysed. The relative risks of associations between obesity and malformations were calculated as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: The prevalence of malformations in children of obese mothers is 11.1% and thus approximately 4% higher than those of the total study population. There is a significant odds ratio for major malformations (OR 1.3; KI 1.0-1.7). Statistically significant associations were calculated for malformations of the internal urogenital system (OR 1.7; 1.1-2.8), the eyes (OR 5.0; 1.3-20.0) and for orofacial clefts (OR 1.7; 1.1-2.8). Among the specific malformations the highest associations occurred for encephalocele (OR 7.3; 1.1-50.6), common truncus arteriosus (OR 6.3; 1.6-24.8) and Potter sequence (OR 6.3; 1.6-24.8). Adjustment for confounding factors (e.g. maternal diabetes mellitus and age) did not change the odds ratios. CONCLUSIONS: Our data demonstrate that newborn of obese mothers are at an increased risk for malformations. An adequate prenatal examination of these pregnancies should include ultrasound screening by specially trained ultrasonographers in tertiary units (DEGUM II/DEGUM III) and serum alpha-fetoprotein measurements. Public health campaigns for prevention are advised.

[Pontine and extra-pontine myelinolysis. Early diagnostic and prognostic value of cerebral CT and MRI]. / Pontine und extrapontine Myelinolysen. Frühdiagnostischer und prognostischer Wert von zerebralem CT und MRT.

Retrospective examination of 44 patients with central pontine and/or extrapontine myelinolysis leads to the conclusion that in early diagnostics cerebral NMR is superior to cCT. T2-weighted images turned out to be the most sensitive parameter. Frequent contrast-medium enhancement early in the course up to 4 weeks after clinical manifestation in 7 patients underlines the pathogenetic idea of an initial transient blood-brain barrier. According to our results, central-pontine myelinolysis (CPM) proof by NMR can be expected after 1 week. During the clinical course, cCT and NMR findings showed no regression. Also no connection was noted between the size of the pontine lesion and the favorable clinical course in 72.2% of the patients, nor was there a correlation with the extent of the neurological symptoms at the crisis of the disease. Altogether, cCT and NMR are irrelevant for the prognosis of cerebral myelinolysis.

Vitamin K deficiency embryopathy: a phenocopy of the warfarin embryopathy due to a disorder of embryonic vitamin K metabolism.

Three unrelated infants presented with radiographic punctate calcifications, nasal hypoplasia, and abnormalities of the spine. Additional anomalies included cupped ears in 2 patients and one each with Dandy-Walker malformation with hydrocephaly, congenital cataracts, and peripheral pulmonary artery stenosis. The mothers of these 3 patients had chronic conditions associated with intestinal malabsorption requiring total parenteral nutrition for varying periods of time. The underlying causes of malabsorption were celiac disease, short bowel syndrome secondary to surgical resection, and jejuno-ileal bypass, respectively. Bleeding diathesis occurred in one mother requiring vitamin K supplementation during the second and third trimesters of pregnancy. We speculate that the chondrodysplasia punctata and other abnormalities in these children were caused by an acquired maternal vitamin K deficiency manifested during early pregnancy. However, the involvement of other vitamin deficiencies cannot be excluded. Thus, vitamin K deficiency of the embryo secondary to maternal malabsorption appears to be a third vitamin K-related mechanism leading to chondrodysplasia punctata in addition to warfarin embryopathy and epoxide reductase deficiency (pseudo-warfarin embryopathy).

Two different PAX3 gene mutations causing Waardenburg syndrome type I.

Waardenburg syndrome (WS) is a form of autosomal dominant inherited deafness combined with specific congenital anomalies. WS types I and III are correlated with mutations in the PAX3 gene on chromosome 2q37. In this report we describe two mutations in the human PAX3 gene causing WS type I in two families. One mutation is an insertion in the paired box domain resulting in a protein termination within the paired box. The second mutation is a base pair substitution producing an arginine to cysteine amino acid change in the homeobox region.

An unknown spondylo-meta-epiphyseal dysplasia in sibs with extreme short stature.

In three sibs of Jordanian descent a unique type of severe spondylo-meta-epiphyseal dysplasia results in extreme disproportionate dwarfism. They have a distinct facial appearance with hypotelorism, prognathia, and hypodontia. The limbs are short and the hands and feet stubby. Radiologically, the irregular end plates of the vertebral bodies, the very small and late appearing epiphyseal ossification centres, and the hypoplastic acetabular roofs are most impressive. Histopathologic studies of the growth plate demonstrate characteristic findings with fingerprint-like inclusion bodies in the hypertrophic chondrocytes. This seems to be a distinct, autosomal recessive skeletal dysplasia.

[The Vogt-Koyanagi-Harada uveomeningoencephalitic syndrome]. / Das uveomeningoenzephalitische Syndrom Vogt-Koyanagi-Harada.

VKHS is an inflammatory system disease with a subacute chronic course. It has a very variable, selective involvement of certain pigment cells of the eye, skin, inner ear, and meninges. Due in part to the fact that its symptoms are responsive to immunosuppressive therapy, pathogenesis as an autoimmune disease is considered. The clinical course of one of our patients is discussed. Early diagnosis of VKHS, although often very difficult, is mandatory for appropriate and timely treatment.

Kniest dysplasia is caused by dominant collagen II (COL2A1) mutations: parental somatic mosaicism manifesting as Stickler phenotype and mild spondyloepiphyseal dysplasia.

We describe two unrelated children with Kniest dysplasia, a severe autosomal dominant form of chondrodysplastic dwarfism associated with cleft palate, progressive arthropathy, myopia and retinal detachment. In the first patient the disorder was caused by a 28 base pair exon 12/intron 12 deletion in the gene coding for type II collagen. Her mother had mild abnormalities of the vertebral bodies and long bones compatible with abnormalities seen in Stickler arthro-ophthalmopathy. The second child had a transition of AG to GG at the 3' splice site of intron 20 of the COL2A1 gene. Her father had premature polvarthrosis interpreted as a sequela of mild spondyloepiphyseal dysplasia. Molecular studies revealed that the mother of the first and the father of the second child each had somatic mosaicism of the same mutation as their children. Heterozygous mutations of the gene coding for type II collagen can cause Kniest dysplasia, and somatic mosaicism for the same mutations can result in the Stickler phenotype or in mild spondyloepiphyseal dysplasia leading to premature polyarthrosis.

Cerebral malformation, seizures, hypertrichosis, distinct face, claw hands, and overlapping fingers in sibs of both sexes.

We report on sibs of both sexes with a multiple malformation syndrome of cerebral malformation, seizures, hypertrichosis, distinct face, claw hands, and overlapping fingers. The older boy died in a tonic extension spasm at age 4 months. When discharged, the younger girl was 3.5 months old. This appears to be an autosomal recessive syndrome which to our knowledge has not been described before.

[A rare differential diagnosis of waddling gait--osteomalacia caused by vitamin D deficiency]. / Seltene Differentialdiagnose des Watschelgangs-Osteomalazie durch Vitamin-D-Mangel.

The so-called "waddling gait" caused by paresis or mechanical insufficiency of the hip muscles is an ambiguous clinical guiding symptom. This pelvifemorally accentuated muscular weakness coinciding with pain in the range of the locomotor system should make one consider the diagnosis of osteomalacia due to deficiency of vitamin D, especially in Asian patients. In the present case, the course of investigation is described in detail, as well as the effective therapy. The diagnosis of this clinical picture ought to be familiar to any neurologist, since its more frequent appearance must be expected as an increasing number of Asians seek asylum in the years ahead. Social integration of the affected persons may be made easier by treatment on the lines described here.

Chondrodysplasia punctata, tibia-metacarpal (MT) type.

We describe 7 patients with a new form of chondrodysplasia punctata. Its principal clinical manifestations are flat midface and nose, short limbs, and otherwise normal development. Consistent radiologic manifestations in the newborn infant are discrete calcific stippling, coronal clefts of vertebral bodies, short tibiae, and shortness of the 2nd and 3rd metacarpal bones. Radiologic findings in the older child include shortness of tibiae and the 3rd and 4th metacarpals.

Spondyloenchondrodysplasia.

Spondyloenchondrodysplasia is a rare autosomal recessive skeletal dysplasia with vertebral dysplasia and enchondroma-like lesions in the pelvis and long bones. The vertebral bodies show dorsally accentuated platyspondyly with disturbance of ossification. Clinical abnormalities such as short stature, rhizomelic micromelia, increased lumbar lordosis, barrel chest, facial anomalies, and clumsy movements may be present. We report on four patients, three of them from one family, who showed a wide range of clinical and radiological changes to document considerable variability of expression of the mutated gene.