Ultrastructural changes in paravertebral muscles associated with degenerative spondylolisthesis.

STUDY DESIGN: The paravertebral muscle of 30 patients with spondylolisthesis and 30 control patients were investigated histologically. OBJECTIVE: To propose myopathologic paravertebral muscle changes in cases of degenerative lumbar spondylolisthesis. SUMMARY OF BACKGROUND DATA: The stability of the vertebral column is based on both active and passive systems. The passive system is composed of the vertebrae, the intervertebral discs, and the ligaments. Surrounding muscles and tendons constitute the active system. The autochthonous back muscles take over support functions if the passive system is ineffective. In some cases, muscles are overstrained for a long period, ultimately leading to muscular changes. This study was performed to determine the histopathologic correlates of this permanent strain. METHODS: Between July 1998 and July 1999, paravertebral muscle biopsies were performed for 30 patients with monosegmental degenerative spondylolisthesis undergoing posterior lumbar interbody fusion. The tissue samples were submitted to histologic analysis including immune and enzyme histochemistry and electron microscopy. In addition, the muscle fibers were submitted to morphometry. RESULTS: Severe pathologic alterations were found. The findings showed that 22 patients (73.3%) had ragged red fibers with evident ultrastructural mitochondrial anomalies. The cristae appeared irregular in 12 patients (40%) Type 1 paracrystalline inclusions were detected in five samples (16.6%) and dense bodies in eight (26.6%). Fibers with ubiquitin-positive inclusions were detected by immunohistochemistry in 13 patients (43.3%). As shown by the electron microscope, these corresponded to granulofilamentous inclusions and polyglucosan bodies. The samples were submitted to genetical analysis because biochemical studies showed reduced activity of the respiratory chain enzymes. Normal mitochondrial deoxyribonucleic acids of unchanged length were detected. CONCLUSIONS: Apart from nonspecific myopathic changes such as those observed in rimmed vacuoles and rods, increased numbers of polyglucosan bodies were detected. This increase in polyglucosan bodies currently has not been described in patients with otherwise normal muscles.

Cerebral hemorrhage after systemic fibrinolysis in a patient with severe carotid artery stenosis.

Despite the beneficial effect of systemic fibrinolysis in treatment within 3 hours from ischemic stroke onset, the unpredicted occurrence of intracerebral hemorrhage remains a risk from such therapy. Few data exist defining patients at risk for this outcome. We report clinical and neuropathological data on a patient fulfilling NINDS rt-PA study and ECASS-2 inclusion criteria with an acute stroke due to high-grade carotid artery stenosis and preceded by amaurosis fugax. He died from an intracerebral hemorrhage after systemic fibrinolysis. The fatal outcome adds support to recommendations that rapid Doppler-sonographic evaluation of the extra- and intracranial vascular status be undertaken before systemic rt-PA is implemented in acute ischemic stroke.

Novel twelve-generation kindred of fatal familial insomnia from germany representing the entire spectrum of disease expression.

We present a novel large German kindred of fatal familial insomnia (FFI) consisting of three branches and comprising more than 800 individuals of 12 generations, the largest pedigree of any familial prion disease known today. There is a wide spectrum of clinical presentations leading to misdiagnoses of Olivo-Ponto-Cerebellar Atrophy (OPCA), Parkinson's or Alzheimer's disease in addition to Creutzfeldt-Jakob disease (CJD) and Gerstmann-Sträussler-Scheinker (GSS) syndrome. Molecular genetic analysis of the prion protein gene (PRNP) confirmed the mutation D178N segregating with methionine at the polymorphic codon 129 of PRNP in all 7 patients examined. This polymorphism at codon 129 is supposed to discriminate between familial CJD (fCJD) and FFI; the 129M allele determines FFI and 129V fCJD. Furthermore, heterozygosity at this site appears to induce prolonged disease duration as compared to the homozygous condition. The variability of the clinical and pathological findings documented for our patients indicates the difficulty in establishing the diagnosis of FFI on clinical and on pathological grounds alone. In three cases (IX-97, XI-21, V-2) followed up by us prospectively insomnia was an early and severe symptom; however, in case notes analyzed retrospectively this symptom was frequently missed. In contrast to previous reports and in agreement with recent studies we cannot confirm a clear relationship between the status of the M/V polymorphism at codon 129 and the age-of-onset of this disease.

Upregulation of vascular endothelial growth factor in severe chronic brain hypoxia of the rat.

The vascular endothelial growth factor (VEGF) has been shown to be upregulated in acute hypoxia. Although an increase in blood vessel number has been described in severe chronic brain hypoxia, it is unclear whether VEGF is upregulated in this condition. We therefore investigated male inbred Wistar rats, which were exposed for 9 to 13 weeks to decreasing amounts of oxygen, down to 7% O2 (15%: 15 days; 12%, 10%, respectively; 8%: 1 day, 3 weeks, respectively; 7%: 4 weeks). The expression of VEGF was studied by Northern analysis and in situ hybridization in frozen sections of cerebral cortex, hippocampus and cerebellum in six chronic hypoxic and two control rats. We found a marked upregulation of VEGF mRNA in all brain regions investigated, being strongest in cerebral cortex and cerebellum. Our results suggest a potential role of VEGF for vascular growth and vascular permeability observed in chronic cerebral hypoxia.

Cerebral angiogenesis triggered by severe chronic hypoxia displays regional differences.

The blood vessels in the brains of adult rats subjected to chronic normobaric hypoxia and control animals housed under normoxic conditions were morphometrically studied. Hypoxic male inbred Wistar rats were exposed over a period of 130 days to decreasing amounts of oxygen starting from 21% down to 7% (15%: 15 days; 12%, 10%, 8%: 22 days, respectively; 7%: 49 days). Areas of cerebral cortex, striatum, hippocampus, cerebellum, and medulla oblongata were investigated. The ratio vessel number per mm2 tissue and the average vessel size were measured using a Quantimet Q570. In the hypoxic animals, cerebral cortex, striatum, and hippocampus showed a significant increase of the vessel density per mm2 tissue (P < 0.01 or P < 0.05). The differences in both groups were highest in the striatum and hippocampus. In the cerebellum and the medulla oblongata of hypoxic animals, only a tendency to higher vessel numbers per mm2 tissue was found. The average blood vessel size differed only in the cerebral cortex and the cerebellum, but not in the other brain regions tested. The results indicate that the adaptation of the brain circulation to hypoxia is achieved by both angiogenesis and dilatation of microvessels, and that the pattern of the microcirculatory changes is not homogenous in all regions.

The relationship between cortical injury and brain tumour. Report of two cases and review of the literature.

We report on two cases of brain tumour and discuss the possible relationship to previous cortical trauma. The first patient, a 67-year-old male patient developed a glioblastoma at the same site of an open shell-splinter injury of the brain after a latency of 48 years. The second patient, a 55-year-old male, had a malignant anaplastic astrocytoma in the right frontal lobe 10 years after clipping of an aneurysm of the anterior communicating artery. Both cases fulfill the criteria of Zülch [52] for the correlation between cortical trauma and tumour. We believe that the development of a brain tumour following a cortical injury is very rare, although possible. Probably the brain must display some form of predisposing genetic alteration for a tumour to develop following a cortical injury.