Myopathy is a prominent feature in Marinesco-Sjögren syndrome

Background

Marinesco–Sjögren syndrome (MSS) is an autosomal recessive multiorgan disorder showing clinical and genetic heterogeneity. The key features of MSS include cerebellar ataxia, early bilateral cataracts, delayed motor development, and varying degrees of mental retardation. Patients with a subtype of MSS with myoglobinuria and neuropathy have been linked to chromosome 18qter, and recently a locus for classical MSS has been localized on chromosome 5q31.

Objectives

To determine the importance of myopathy in this disorder apart from the CNS based disability and to establish the pattern of muscle involvement and degree of its severity.

Methods

Muscle computed tomography (CT) investigations were carried out in nine Finnish MSS patients homozygous for markers around the MSS locus on chromosome 5q31.

Results

Patients with severe clinical disability showed severe and generalized muscle degeneration. Muscle CT findings in patients with relatively severe clinical picture were characterized by severe involvement of the posterior thoracic and pelvic muscles, and almost all thigh muscles. In the legs the peronei and posterior compartment muscles were severely degenerated. The group of patients with moderate severity of disease showed the same pattern of involved muscle, albeit with lower degree of muscle degeneration.

Conclusions

Patients with MSS linked to chromosome 5q31 have a severe progressive myopathy, the extent of which may remain largely unrecognized because of the CNS involvement.     

Outcome of fractionated stereotactic radiotherapy in patients with pituitary adenomas resistant to conventional treatments: a 5·25‐year follow‐up study

Objective To investigate the long‐term outcome of fractionated stereotactic radiotherapy (FSRT) [45 Gy (range 45–54) in 25 fractions] in patients with pituitary adenomas characterized by tumour progression or hormonally active disease despite surgery and/or medical therapy. Design This was an observational follow‐up study of 5·25 years (median; range 1·7–10·4). Patients and measurements Pituitary tumour volume, visual acuity/fields, hypersecretion, hypopituitarism, cerebrovascular disease, second brain tumours and mortality were examined at regular intervals after FSRT in 30 patients with pituitary adenomas (20 nonfunctioning macroadenomas, 10 functioning). Prior to FSRT, 83% had been operated 1–3 times, 47% had visual field deficits/impaired vision and 50% pituitary dysfunction. Progressive disease, stable disease, partial and complete tumour response were defined by MRI. Results Tumour growth control was 100%. At the end of follow‐up, 30% had stable disease, 60% partial and 10% complete tumour response. Visual function was preserved and 36% of patients with prior field deficits improved. GH decreased from 4·2 (range, 2·3–6·5) to 1·1 (range, 0·5–1·5) μg/l (P < 0·001) in patients with acromegaly, and medical therapy could be reduced. In large prolactinomas, partial response or complete tumour response was achieved. FSRT was well tolerated. Pituitary function remained normal in 27%, 33% of patients had stable dysfunction, 17% deteriorated further and 23% developed new dysfunction. There were no cerebrovascular events, second brain tumours or FSRT‐related deaths. Conclusion According to this long‐term follow‐up study, FSRT is an efficient and safe adjuvant therapy for pituitary adenomas refractory to conventional treatments.     

Distribution of endothelial and basement membrane markers in angiogenic tumors of the nervous system

The distribution of two endothelial cell markers Factor-VIII-related antigen and Ulex europaeus agglutinin was examined by immunoperoxidase and immunofluorescence techniques in paraffin-embedded specimens representing the three main types of angiogenic neoplasms of the nervous system, hemangioblastoma, hemangioendothelioma and hemangiopericytoma. In addition, the distribution of the basement membrane (BM) marker, laminin, was studied in the same tumors. It was found that Ulex europaeus agglutinin was a more sensitive marker of neoplastic endothelial cells than Factor-VIII-related antigen. Both markers only stained endothelial cells, while the tumor cells of hemangiopericytomas and the stromal cells of hemangioblastomas remained unstained. These findings do not support the view that the stromal cells of hemangioblastomas are derived from endothelial cells. With antiserum to laminin a typical staining pattern could be noticed in each tumor, showing the architectural relationships of the cells very clearly. In all three tumor types laminin was only found in the BM of the vessels, not in the interstices of the neoplastic cells outside vessel lumina. Therefore, the reticulin network previously found between the individual cells of hemangiopericytomas does not correspond to BM. It is concluded that both Ulex europaeus agglutinin and laminin antisera could be valuable new aids for the diagnosis of the three tumor types.     

Histopathological differences of myotonic dystrophy type 1 (DM1) and PROMM/DM2

Muscle biopsy findings in DM2 have been reported to be similar to those in DM1. The authors used myosin heavy chain immunohistochemistry and enzyme histochemistry for fiber type differentiation on muscle biopsies. Their results show that DM2 patients display a subpopulation of type 2 nuclear clump and other very small fibers and, hence, preferential type 2 fiber atrophy in contrast to type 1 fiber atrophy in DM1 patients.     

Nd-YAG laser in subtotal thyroidectomy: A prospective randomized study

Thirty patients for thyroid resection were allocated into conventional (n=15) or laser (n=15) operations. The age and sex distribution were similar, as was the relation between unilateral and bilateral resections between the groups. A contact Nd-YAG laser was used for dissection and resection in the laser group, where there was significantly less bleeding than in the conventional group (p<0.05). The operation was also faster in the laser group. No complications occurred. It is concluded that the contact Nd-YAG laser technique can safely be used in resection of the thyroid gland.     

Variant Alzheimer's disease with spastic paraparesis and cotton wool plaques is caused by PS-1 mutations that lead to exceptionally high amyloid-beta concentrations

We describe 3 new families affected by Alzheimer's disease with spastic paraparesis. In affected individuals, including the earliest known patient with this clinical syndrome, neuropathological examination revealed large "cotton wool" plaques similar to those we have previously described in a Finnish family. In the families in which DNA was available, presenilin-1 mutations were observed. Transfection of cells with these mutant genes caused exceptionally large increases in secreted Abeta42 levels. Furthermore, brain tissue from individuals with this syndrome had very high amyloid-beta concentrations. These findings define the molecular pathogenesis of an important subgroup of Alzheimer's disease and have implications for the pathogenesis of the disease in general.     

Boron neutron capture therapy of brain tumors: clinical trials at the finnish facility using boronophenylalanine

Summary Two clinical trials are currently running at the Finnish dedicated boron neutron capture therapy (BNCT) facility. Between May 1999 and December 2001, 18 patients with supratentorial glioblastoma were treated with boronophenylalanine (BPA)-based BNCT within a context of a prospective clinical trial (protocol P-01). All patients underwent prior surgery, but none had received conventional radiotherapy or cancer chemotherapy before BNCT. BPA-fructose was given as 2-h infusion at BPA-dosages ranging from 290 to 400 mg/kg prior to neutron beam irradiation, which was given as a single fraction from two fields. The average planning target volume dose ranged from 30 to 61 Gy (W), and the average normal brain dose from 3 to 6 Gy (W). The treatment was generally well tolerated, and none of the patients have died during the first months following BNCT. The estimated 1-year overall survival is 61%. In another trial (protocol P-03), three patients with recurring or progressing glioblastoma following surgery and conventional cranial radiotherapy to 50–60 Gy, were treated with BPA-based BNCT using the BPA dosage of 290 mg/kg. The average planning target dose in these patients was 25–29 Gy (W), and the average whole brain dose 2–3 Gy (W). All three patients tolerated brain reirradiation with BNCT, and none died during the first three months following BNCT. We conclude that BPA-based BNCT has been relatively well tolerated both in previously irradiated and unirradiated glioblastoma patients. Efficacy comparisons with conventional photo radiation are difficult due to patient selection and confounding factors such as other treatments given, but the results support continuation of clinical research on BPA-based BNCT.