Cobblestone-like brain dysgenesis and altered glycosylation in congenital cutis laxa, Debre type.

OBJECTIVE: To delineate a new syndrome of brain dysgenesis and cutis laxa based on the description of 11 patients belonging to nine unrelated families recruited through an international collaboration effort. METHODS: Careful clinical assessment of patients from birth to the age of 23 years with follow-up studies ranging from 3 to 20 years. Biochemical studies of serum proteins glycosylation by isoelectric focusing and capillary zone electrophoresis were performed in 10 patients. Brain MRI studies using conventional methods were analyzed in eight patients. RESULTS: An expanded clinical spectrum of a syndrome comprising facial dysmorphia (enlarged anterior fontanelles, downward slant of palpebral fissures, prominent root of the nose), a connective tissue disorder (inguinal hernia, hip dislocation, high myopia), and neurologic impairment was defined. Early developmental delay was followed by onset of generalized seizures by the end of the first decade and a subsequent neurodegenerative course. A defect of N- or N- plus O-glycosylation of serum transferrins and ApoCIII was observed in 10 patients. An unusual cobblestone-like cortical malformation over the frontal and parietal regions was seen in eight patients and cerebellar abnormalities, including two patients with Dandy-Walker malformation, were observed in three patients. CONCLUSIONS: Our results suggest that autosomal recessive cutis laxa, Debré type, initially considered a dermatologic syndrome, is a multisystemic disorder with cobblestone-like brain dysgenesis manifesting as developmental delay and an epileptic neurodegenerative syndrome. It might represent a metabolic cause of Dandy-Walker malformation. It is associated with a deficient N- and-O glycosylation of proteins and shares many similarities with muscle-eye-brain syndromes.

Almotriptan and its combination with aceclofenac for migraine attacks: a study of efficacy and the influence of auto-evaluated brush allodynia.

Early treatment and combining a triptan with a non-steroidal anti-inflammatory drug (NSAID) are thought to improve outcome during migraine attacks, possibly by counteracting the negative influence of cutaneous allodynia. The aim of this multicentre, double-blind pilot study was to evaluate the prevalence of brush allodynia and its relative influence on the efficacy of a triptan-NSAID combination compared with headache intensity at the time of treatment. In a randomized, cross-over design, 112 migraineurs treated two moderate or severe attacks with almotriptan 12.5 mg combined with either aceclofenac 100 mg or placebo. Patients used a 2-cm brush to assess cutaneous allodynia. Allodynia was reported in 34.4% of attacks. The almotriptan-aceclofenac combination was numerically superior to triptan-placebo on 2-24-h sustained pain-free (P = 0.07), 2-h pain-free (P = 0.07) and headache recurrence (P = 0.05) rates, but not on 1-h headache relief. Allodynia numerically reduced treatment success overall, but this effect was not significant for the primary outcome measures. Headache intensity had a significant negative influence on 1-h relief in both attacks (P = 0.0001 and 0.0008, chi(2)) and on 2-24-h sustained pain-free rates in triptan-placebo-treated attacks (P = 0.013). Multivariate logistic regression analysis confirmed that headache intensity at treatment intake, rather than allodynia, significantly influenced most outcome measures, predominantly so in attacks treated with almotriptan and aceclofenac. In the latter, severe compared with moderate headache intensity reduced the likelihood of achieving the primary efficacy end-points [odds ratios (OR) 0.12 and 0.33], whereas allodynia was not a significant explanatory variable (OR 0.76 and 0.65). The results apply to the protocol used here and need to be confirmed in larger studies using quantitative sensory testing.

Two cases of maternal antenatal splenic rupture and hypotension associated with Moebius syndrome and cerebral palsy in offspring. Further evidence for a utero placental vascular aetiology for the Moebius syndrome and some cases of cerebral palsy.

UNLABELLED: We wish to report two cases of congenital abnormality after antenatal car accidents resulting in ruptured spleen and severe hypotension in the mothers at 8 and 14 weeks gestation. The first case had the classical Moebius syndrome with 6th and 7th cranial nerve palsy with abnormal brain stem evoked responses, presumably due to hypoxic/ischaemic brain stem damage and the second case had severe retardation and hypertonic cerebral palsy which at post mortem was found to be due to old hypoxic/ischaemic lesions to the caudate nucleus putamen and striatum. CONCLUSION: The cases described provide evidence that severe maternal hypotension during pregnancy can be associated with lesions to the midbrain and brain stem of offspring. The mechanism is probably utero-placental insufficiency, and extrapolation from these two unusual cases would support utero-placental insufficiency as a cause of Moebius syndrome and limb deficiency after chorionic villus sampling.

The influence of ototoxic drugs on brainstem auditory evoked potentials in man.

To examine the short- and long-term consequences of ototoxic drug administration, the brainstem auditory evoked potentials (BAEP) have been recorded in patients undergoing treatment with aminoglycosides antibiotics. It appears that the rapidity of the i.v. injection influences the short-term consequences of the drug administration. The long-term consequences may be reversible. Their reversibility could depend on the status of the ear before the first injection of ototoxic drug. In conclusion, BAEP may be useful as a means of atraumatic monitoring of the auditory function of patients treated with aminoglycosides antibiotics, the non-invasive character of this technique allowing it to be repeatedly used in both adult and young patients.