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Background: Due to the growing use of artificial respiration in amyotrophic lateral sclerosis (ALS), physicians are increasingly confronted with patients seeking discontinuation of therapy. Yet there are few systematic investigations of the withdrawal of ventilation therapy., Patients and Methods: In a retrospective investigation of nine German ALS patients, clinical data were recorded from the discontinuation of noninvasive ventilation (n=4) and mechanical ventilation (n=5)., Results: In cases of residual spontaneous breathing, intensified symptom control of dyspnea and anxiety was possible with intravenous morphine sulfate at a low dose rate (10 mg/h) but high cumulative dose (185-380 mg). The terminal phase after removing the mask was protracted (22:10 h to 28:00 h). In cases of minimal or absent spontaneous breathing the disconnection was realized in deep sedation, which required a moderate total dose of morphine sulfate (120 mg) but a high dosage rate (up to 300 mg/h). The terminal phase in deep sedation was short (15-80 min)., Conclusion: The elective termination of ventilation requires differentiated pharmacologic palliative care. More controlled studies are required in order to establish evidence-based guidelines for the termination of ventilation.

Thin corpus callosum has been recently observed in two patients with an autosomal dominant trait of hereditary spastic paraplegia (HSP) linked to a novel mutation in the spastin gene (SPG4). In the same two patients cerebellar atrophy has been found. Reportedly, in other members of the same family, there has been a variable presence of mental retardation. We report on the clinical and genetic investigation of an Austrian family with a novel mutation in the spastin gene. Genetic analysis of the SPG4 locus revealed a mutation (C1120A) and a known intronic polymorphism (996-47G>A) of the spastin gene. In one affected family member, previously undescribed dysplasia of the corpus callosum (CC) was found in conjunction with otherwise uncomplicated HSP. Dysplastic CC was not paralleled with cortical atrophy, cognitive impairment or other phenotypic variations. Two further affected family members showed the same mutation and polymorphism, but no evidence of CC abnormalities. We conclude that apparently pure HSP may present with MRI features of dysplastic CC. This finding extended the spastin-related phenotype which is distinct from previous reports of thin CC in HSP.

Recent identification of ion channel gene mutations in Mendelian epilepsies suggests that genetically driven neuronal hyperexcitability plays an important role in epileptogenesis. In this study, we tested the hypothesis that genetic variation in the human SCN2B gene confers liability to common subtypes of idiopathic generalized epilepsies (IGE). A systematic search for mutations was performed in 92 IGE patients. We detected a novel single nucleotide polymorphism (SNP), however, allele frequencies did not differ between IGE patients and controls (chi2 = 0.19, df = 1, p = 0.744). Furthermore, a missense mutation in codon 209 (Asn209Pro) was identified in one patient, but was found to be absent in an affected sibling of the index patient. Thus, our results do not suggest a major role of the SCN2B gene in the etiology of common IGE subtypes.