Our results suggest a significant association between recent infection and CAD that is not explained by mechanical factors occurring during infection.

CAD is associated with ultrastructural connective tissue abnormalities, mostly without other clinical manifestations of a connective tissue disease. A structural defect in the extracellular matrix of the arterial wall leading to a genetic predisposition is suggested. The dermal connective tissue abnormalities detected can serve as a phenotypic marker for further genetic studies in patients with CAD and large families to possibly identify the underlying basic molecular defect(s).

The cause of spontaneous cervicocerebral artery dissection is unknown. An underlying arteriopathy due to a connective tissue disorder has often been presumed. We studied 25 patients with proven nontraumatic dissections. The ultrastructural morphology of dermal connective tissue components was assessed by transmission electron microscopy of skin biopsies. Ultrastructural abnormalities were seen in 17 (68%) patients, resembling in some cases the aberrations found in Ehlers-Danlos syndrome type II or III. These observations indicate a correlation of cervical artery dissections with connective tissue abnormalities. A structural abnormality in the extracellular matrix potentially caused by basic molecular defects is suggested and warrants further exploration.

Background and Purpose-The dermal connective tissue of most patients with spontaneous cervical artery dissections (sCAD) contains abnormal collagen fibers. This suggests a predisposing connective tissue defect. The ultrastructural abnormalities in the skin of patients with sCAD have similarity with the morphological alterations in patients with Ehlers-Danlos syndrome type II, a dominant hereditary disorder that has been correlated in some patients to mutations within the genes encoding type V collagen. The aim of this study was to assess the alpha 1 chain of type V collagen (COL5A1) as a candidate gene for sCAD. Methods-We searched for mutations in the COL5A1 gene in cDNA from cultured fibroblasts of 19 patients with sCAD using single-strand conformational polymorphism analysis and nucleotide sequence analysis of polymerase chain reaction-amplified fragments of the whole COL5A1 coding sequence. Results-We detected 1 missense mutation leading to a predicted amino acid (192D/N) substitution within the N-terminal propeptide in 2 siblings. All other patients showed regular COL5A1 sequences with some silent polymorphisms. Conclusions-Mutations in the COL5A1 gene do not appear to be a major factor in the etiology of sCAD. (Stroke.1999;30:1887-1890.)Key Words: connective tissue disorders Ⅲ dissection Ⅲ genetics Ⅲ mutation S pontaneous cervical artery dissections (sCAD) are increasingly recognized as a cause of stroke among young and middle-aged patients. 1 A predisposing arteriopathy in these patients has been postulated. 2 A recent study by Brandt et al 3 substantiated the hypothesis of a predisposing defect in the extracellular matrix. These authors found ultrastructural abnormalities in skin biopsies of a majority of patients with sCAD and suggested an association with a connective tissue disorder. Major findings included numerous enlarged and irregular collagen fibrils and pronounced elastic fiber fragmentation. The abnormalities resembled the morphological alterations in patients with Ehlers-Danlos syndrome type II or III (EDS II/III). 4 Those changes were not observed in age-matched stroke patients with alternative etiologies of cerebral ischemic infarcts or in healthy control subjects. None of the patients with sCAD had other phenotypic manifestations of a known hereditary connective tissue disorder.Type V collagen belongs to the family of fibrillar collagens. [5][6][7] It is expressed at a low level in many tissues and plays an important role in type I fibrillogenesis by modulating and influencing fibril diameter. 8 -9 Mutations in COL5A1 and COL5A2 may lead to ultrastructural abnormalities similar to those observed in sCAD patients. 10 Furthermore, some patients with EDS I/II carry mutations in the COL5A1or the COL5A2 gene (for reference, see Michalickova et al 11 ). The ultrastructural similarities of dermal connective tissue aberrations of EDS II patients and sCAD patients prompted us to start this study and to analyze the full coding sequence of COL5A1 in patients with sCAD. Subjects and MethodsWe investig...

The intracranial space is divided into two large compartments by the tentorium. The hydrostatic pressure of spinal fluid is responsible for buoyancy of the brain within these compartments. In patients with craniectomy this equilibrium is exposed to atmospheric pressure. We report on four cases of reversible herniation after either bilateral or unilateral decompressive craniectomy performed for increased intracranial pressure (ICP) and failure of conservative ICP treatment. All four patients had survived a severe neurological disease (encephalitis, subdural haematoma, stroke) which required craniectomy to control raised ICP. All were successfully weaned from the ventilator and awake and CT scans showed no space-occupying lesion anymore. The patients showed a typical "sunken pattern" at the trepanation site. All patients developed clinical signs of transtentorial herniation (i.e. unilateral dilated pupils, deteriorated alertness, and extensor posturing) shortly after either diagnostic or presumed therapeutic lumbar puncture. One patient developed herniation a second time while in the typical 30 degrees upright position. After craniectomy, transtentorial herniation is possible even in the absence of increased ICP. It is related to a negative gradient between atmospheric and intracranial pressure, which is enhanced by changes in the CSF compartment following lumbar puncture. Lumbar puncture should be avoided if possible and, when necessary, only be performed in the head-down position. Acute therapy in these cases is quite simple; it requires flat or even head-down positioning and early cranioplasty.