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STUDY OBJECTIVES: To analyze (1) the impact of a protocol of early respiratory evaluation of the indications for home mechanical ventilation (HMV) in patients with amyotrophic lateral sclerosis (ALS), and (2) the effects of the protocol and of bulbar involvement on the survival of patients receiving noninvasive ventilation (NIV). DESIGN AND SETTING: Retrospective study in a tertiary care referral center. PATIENTS: HMV was indicated in 86 patients with ALS, with 22 patients (25%) presenting with intolerance to treatment associated with bulbar involvement. Treatment with HMV had been initiated in 15 of 64 patients prior to initiating the protocol (group A) and in the remaining 49 patients after protocol initiation (group B). RESULTS: In group A, the majority of patients began treatment with HMV during an acute episode requiring ICU admission (p = 0.001) and tracheal ventilation (p = 0.025), with a lower percentage of patients beginning HMV treatment without respiratory insufficiency (p = 0.013). No significant differences in survival rates were found between groups A and B among patients treated with NIV. Greater survival was observed in group B (p = 0.03) when patients with bulbar involvement were excluded (96%). Patients without bulbar involvement at the start of therapy with NIV presented a significantly better survival rate (p = 0.03). Multivariate analysis showed bulbar involvement to be an independent prognostic factor for survival (relative risk, 1.6; 95% confidence interval, 1.01 to 2.54; p = 0.04). No significant differences in survival were observed between patients with bulbar involvement following treatment with NIV and those with intolerance, except for the subgroup of patients who began NIV treatment with hypercapnia (p = 0.0002). CONCLUSIONS: Early systematic respiratory evaluation in patients with ALS is necessary to improve the results of HMV. Further studies are required to confirm the benefits of NIV treatment in patients with bulbar involvement, especially in the early stages. [ABSTRACT FROM AUTHOR]

In POEMS syndrome the identification and biopsy of an osteosclerotic lesion or a lymph node typical of Castleman's disease (CD) is essential to establish the diagnosis and plan appropriate treatment. We report four patients in whom the localisation and identification of diagnostic bone lesions or lymphadenopathies were guided by fluorodeoxyglucose positron emission tomography integrated with computerised tomography (FDG PET/CT). FDG PET/CT identified bone lesions not detected with other techniques in one patient, and revealed hypermetabolic characteristics in bone lesions or adenopathies in the others, thus guiding the diagnostic biopsy in those with hypermetabolism. In conclusion, FDG PET/CT may be useful in detecting and selecting bone lesions and lymph nodes for biopsy in patients with suspected POEMS syndrome., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

A 27-year-old woman of Moldavian origin presented at the age of 15 with progressive proximal limb weakness and painful cramps in her calf muscles. Clinical examination revealed prominent muscle weakness in proximal muscles of the lower extremities and distal anterior compartment of legs, and mild weakness in shoulder girdle muscles. In addition, she had marked calf hypertrophy, muscle atrophy involving the anterior and posterior compartments of the thighs, and the distal anterior compartment of legs, as well as mild scapular winging and hyperlordosis. A muscle biopsy taken from the biceps brachii showed mild dystrophic changes, absent vacuoles, and abundant lobulated fibers. Immunofluorescence and Western blot assays demonstrated complete telethonin deficiency. Molecular analysis revealed a homozygous Trp25X mutation in the telethonin (TCAP) gene resulting in termination of transcription at an early point. Four families from Brazil with telethonin deficiency have previously been reported and classified as LGMD2G, but the actual frequency of this disease is unknown. With this current identification of a case outside the Brazilian population, telethonin mutation-associated LGMD should be considered worldwide.

Immunohistochemical studies using antibodies to myogenic regulatory factors (MRFs) Myo D, myogenin, myf-5, and myf-6, and transcription factors c-Fos and c-Jun, were performed on muscle biopsies from patients suffering from Duchenne and Becker muscular dystrophies, polymyositis, and denervation atrophy, to investigate whether expression of these factors occurs during degeneration and regeneration of adult muscle fibres. Strong Myo D, myogenin, myf-5 and myf-6 immunoreactivity was observed in the nuclei of small regenerating fibres and satellite cells, as revealed by double-labelling immunohistochemistry with N-CAM antibodies, in Duchenne and Becker muscular dystrophies and in polymyositis. This suggests that the myogenic programme is activated during regeneration of adult human muscle fibres. In addition, strong myf-6 and c-Jun immunoreactivity was found in the cytoplasm of some necrotic muscle fibres in patients with Duchenne and Becker muscular dystrophies and in patients with polymyositis. The latter findings suggest that strong cytoplasmic expression of myf-6 and c-Jun is related to the process of muscle fibre degeneration that occurs in these conditions. Increased Myo D, myogenin, myf-5 and myf-6 immunoreactivity was not observed in the nuclei of denervated muscle fibres, although strong c-Fos and c-Jun immunoreactivity was seen in the nuclei of denervated muscle fibres; this suggests that denervation triggers the expression of these transcription factors. Taken together, these observations demonstrate that MRFs and c-Fos and c-Jun are selectively expressed in different human muscular disorders.

Muscle biopsies from patients affected by muscular dystrophies and polymyositis were processed with the method of in situ labeling of nuclear DNA fragmentation in order to assess whether apoptosis occurs in these diseases. Apoptotic nuclei were seen in the mononuclear cell infiltrates in inflammatory myopathies but not in dying muscle fibers, thus confirming the general opinion that death of muscle fibers in human diseases is not produced by a mechanism of apoptosis.

The development of non-pyramidal neurons was studied in the rat sensorymotor cortex during the fetal and early postnatal periods with Golgi's method. Additional data of the early stages were obtained using autoradiography and electron microscopy. Horizontal neurons in the marginal layer were found from the 15th postconceptional (pc.) day (cellular birthday: 13th-15th pc. day). Horizontal neurons in the inner margin of the early cortical plate were found from the 16th pc. day (cellular birthday: 14th-16th pc. day). Coarse cell profiles were seen with Golgi's method, but, under electron microscope, increased numbers of organelles were observed in these cells, as compared to those of the cortical plate. From the 17th day of gestational age to the moment of birth, a small number of non-pyramidal neurons were stained with Golgi's method, including horizontal, stellate, and neurogliform neurons, at different levels of the cortical plate. The greatest development of the non-pyramidal system was observed during the second postnatal week, while the greatest increase of dendritic branches and synaptic spines was observed during the third and fourth weeks. This pattern is similar to that observed in the pyramidal system, but an ascending gradient was not observed.

A 49-year-old man developed mononeuritis multiplex associated with angioimmunoblastic lymphadenopathy. The biopsy of the sural nerve revealed focal reduction of myelinated fibres and axonal degeneration, as well as perivascular inflammatory infiltrates composed of lymphocytes and plasma cells, exhibiting policlonal immunoglobulin expression, proliferation of blood vessels, thickening of the vessel wall and endothelial hyperplasia. These latter changes are similar to those commonly encountered in the lymph nodes, as well as in other organs, in patients suffering from angioimmunoblastic lymphadenopathy.