Open-Label Allopregnanolone Treatment of Men with Fragile X-Associated Tremor/Ataxia Syndrome.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder affecting approximately 45% of male and 16% of female carriers of the FMR1 premutation over the age of 50 years. Currently, no effective treatment is available. We performed an open-label intervention study to assess whether allopregnanolone, a neurosteroid promoting regeneration and repair, can improve clinical symptoms, brain activity, and magnetic resonance imaging (MRI) measurements in patients with FXTAS. Six patients underwent weekly intravenous infusions of allopregnanolone (2-6 mg over 30 min) for 12 weeks. All patients completed baseline and follow-up studies, though MRI scans were not collected from 1 patient because of MRI contraindications. The MRI scans from previous visits, along with scans from 8 age-matched male controls, were also included to establish patients' baseline condition as a reference. Functional outcomes included quantitative measurements of tremor and ataxia and neuropsychological evaluations. Brain activity consisted of event-related potential N400 word repetition effect during a semantic memory processing task. Structural MRI outcomes comprised volumes of the hippocampus, amygdala, and fluid-attenuated inversion recovery hyperintensities, and microstructural integrity of the corpus callosum. The results of the study showed that allopregnanolone infusions were well tolerated in all subjects. Before treatment, the patients disclosed impairment in executive function, verbal fluency and learning, and progressive deterioration of all MRI measurements. After treatment, the patients demonstrated improvement in executive functioning, episodic memory and learning, and increased N400 repetition effect amplitude. Although MRI changes were not significant as a group, both improved and deteriorated MRI measurements occurred in individual patients in contrast to uniform deterioration before the treatment. Significant correlations between baseline MRI measurements and changes in neuropsychological test scores indicated the effects of allopregnanolone on improving executive function, learning, and memory for patients with relatively preserved hippocampus and corpus callosum, while reducing psychological symptoms for patients with small hippocampi and amygdalae. The findings show the promise of allopregnanolone in improving cognitive functioning in patients with FXTAS and in partially alleviating some aspects of neurodegeneration. Further studies are needed to verify the efficacy of allopregnanolone for treating FXTAS.

Intensive respiratory care service. Organisation, orientation, system and future. Our experience of management of 288 cases.

Between Jan. 1983 and Dec. 1986, 288 patients with acute respiratory failure of varied aetiologies were admitted to tetanus and respiratory care ward. One hundred and twenty patients (41.66%) had primary respiratory diseases, 107 (37.15%) of poisoning, 24 (8.3%) had neuromuscular diseases and 37 (12.48%) had miscellaneous disorders. Ventilatory support was given for more than 6 hours to 118 patients. The overall survival was 61.81% and on ventilator 38.13%. The mortality was high with ARDS (100%), miscellaneous (100%) pneumonia with septicaemia (75%) and COAD (54.28%). Patient with COAD had high mortality with acidosis (pH less than 7.1, P less than 0.01), hypotension (systolic BP less than 90 mm of Hg, p less than 0.05) and oliguria (urine out put less than 400 ml/24 hours, p less than 0.05). Organophosphorus compound was the commonest poison (89.75%) and patients who had moderate to severe hypoxia (pO2 less than 60 mm of Hg), hypotension and an interval of more than 4 hours between the consumption of poison and admission (all P less than 0.05) expired; 68.18% expired within the first 72 hours. All the patients with primary neuromuscular paralysis and bronchial asthma survived. Hospital acquired infections (160 patients), retained secretions (108 patients) and hypotension (64 patients) were the commonest complications seen in the 288 patients. Staphylococcus aureus (32.14%) was the commonest organism isolated. Financial constraints, drug shortages and frequent failure of machines were other major problems in the intensive respiratory care unit.