In order to define the patterns of neurological involvement in Behcet's disease and to assess prognostic factors, 558 files of the neuro-Behcet out-patient clinic were reviewed. Those patients without any evidence of objective neurological involvement as well as the patients with other possible explanations for the neurological picture, and cases not fulfilling the criteria for Behcet's disease were excluded. The remaining 200 cases (155 male, 45 female) were evaluated: 162 had parenchymal CNS involvement (brainstem or 'brainstem +' involvement in 51%, spinal cord involvement in 14%, hemispheric involvement in 15% and isolated pyramidal signs in 19%) while 38 had secondary or non-parenchymal CNS involvement. In the first group the most common findings were pyramidal signs, hemiparesis, behavioural changes and sphincter disturbance, whereas in the second group the syndrome of raised intracranial pressure due to dural sinus thrombosis was the main clinical manifestation. In 60% of the cases with parenchymal involvement, CSF was hypercellular and/or had an elevated protein level, whereas in cases with non-parenchymal involvement the CSF was usually normal except for the elevated pressure. In more than half of the patients with parenchymal involvement, MRI showed brainstem and/or basal ganglion lesions. Forty-one per cent of the cases had a course with at least one attack and remission, another 28% also had attack(s) but showed secondary progression, 10% had primary progression and 21% had silent neurological involvement. Survival analysis was performed in patients who had at least a 3-year duration of neurological disease. Parenchymal involvement, elevated protein and/or pleocytosis in the CSF, 'brainstem +' type involvement, primary or secondary progressive course and relapse during steroid tapering were all associated with a poorer prognosis.

Clinical patterns of neurological involvement in Behçet's disease: evaluation of 200 patients. The Neuro-Behçet Study Group.

BACKGROUND AND PURPOSE: Behcet disease (BD) is a multisystem vasculitis of unknown origin in which neurologic involvement has been reported in the range of 5% to 10% in large series. Reports on clinical and radiologic aspects of neuro-Behcet syndrome (NBS) are in general limited in number. Our purpose was to determine the MR patterns in patients with NBS who had neural parenchymal involvement and to correlate our findings with possible vascular pathophysiology. METHODS: The MR images of 65 patients with NBS and neural parenchymal involvement were reviewed. In a subgroup of patients who had serial MR studies, we evaluated the anatomic-radiologic location and distribution of the lesions and whether they corresponded to any vascular territory, and studied their extension, enhancement patterns, and temporal course. RESULTS: The most common imaging finding in NBS patients who had neural parenchymal involvement was a mesodiencephalic junction lesion with edema extending along certain long tracts in the brain stem and diencephalon in 46% of the patients. The next most common location of involvement was the pontobulbar region, seen in 40% of the cases. Three primary cervical spinal cord lesions and one case of isolated optic nerve involvement were observed. CONCLUSION: The parenchymal distribution of lesions in NBS appears to support the hypothesis of small-vessel vasculitis; mainly, venular involvement. The anatomic distribution of intraaxial veins of the CNS explains the predominant involvement of the brain stem structures observed in our patients. This pattern of lesion distribution might help to differentiate NBS from other vasculitides as well as from the inflammatory-demyelinating diseases of the CNS, such as multiple sclerosis.

http://www.ajnr.org/content/ajnr/20/6/1015.full.pdf

CNS involvement in neuro-Behçet syndrome: an MR study.

To test the hypothesis that genetic factors can determine susceptibility to hypertension-induced renal damage, we derived an experimental animal model in which two genetically different yet histocompatible kidneys are chronically and simultaneously exposed to the same blood pressure profile and metabolic environment within the same host. Kidneys from normotensive Brown Norway rats were transplanted into unilaterally nephrectomized spontaneously hypertensive rats (SHR-RT1.N strain) that harbor the major histocompatibility complex of the Brown Norway strain. 25 d after the induction of severe hypertension with deoxycorticosterone acetate and salt, proteinuria, impaired glomerular filtration rate, and extensive vascular and glomerular injury were observed in the Brown Norway donor kidneys, but not in the SHR-RT1.N kidneys. Control experiments demonstrated that the strain differences in kidney damage could not be attributed to effects of transplantation-induced renal injury, immunologic rejection phenomena, or preexisting strain differences in blood pressure. These studies (a) demonstrate that the kidney of the normotensive Brown Norway rat is inherently much more susceptible to hypertension-induced damage than is the kidney of the spontaneously hypertensive rat, and (b) establish the feasibility of using organ-specific genome transplants to map genes expressed in the kidney that determine susceptibility to hypertension-induced renal injury in the rat.

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Genetic susceptibility to hypertension-induced renal damage in the rat. Evidence based on kidney-specific genome transfer.

Age-related morphologic development of human adrenal zona reticularis (ZR) has not been well examined. Therefore, in this study, 44 human young adrenal autopsy specimens retrieved from large archival files (nZ252) were examined for immunohistochemical and morphometric analyses. Results demonstrated that ZR became discernible around 4 years of age, and both thickness and ratio per total cortex of ZR increased in an age-dependent fashion thereafter, although there was no significant increment in total thickness of developing adrenal cortex. We further evaluated immunoreactivity of both KI67 and BCL2 in order to clarify the equilibrium between cell proliferation and apoptosis in the homeostasis of developing human adrenals. Results demonstrated that proliferative adrenocortical cells were predominantly detected in the zona glomerulosa and partly in outer zona fasciculata (ZF) before 4 years of age and in ZR after 4 years of age, but the number of these cells markedly decreased around 20 years of age. The number of BCL2positive cells increased in ZR and decreased in ZF during development. Adrenal androgen synthesizing type 5 17bhydroxysteroid dehydrogenase (HSD17B5 or AKR1C3 as listed in the Hugo Database) was almost confined to ZR of human adrenals throughout development. HSD17B5 immunoreactivity in ZR became discernible and increased from around 9 years of age. Results of our present study support the theory of age-dependent adrenocortical cell migration and also indicated that ZR development is not only associated with adrenarche, but may play important roles in an initiation of puberty.

/pdf/development-of-the-human-adrenal-zona-reticularis-5cwhbfosu0.pdf

Development of the human adrenal zona reticularis: morphometric and immunohistochemical studies from birth to adolescence

Tissue remodelling in the adrenal gland.

This report consists of two cases who died after a neurological disorder of the central nervous system consistent with Behcet's disease clinically and pathologically. Post-mortem examination of the central nervous system revealed mild diffuse meningo- encephalitis with multiple foci of softening, demyelination and glial cell accumulation in the pons, midbrain, cerebral peduncle and internal capsule. The significance of these morphological findings has been discussed from an etiological viewpoint of Neuro-Behcet's syndrome.

Neuro-Behçet's syndrome: report of two autopsy cases.

The development and tissue differentiation of the adrenal cortex of rats were studied by giving experimental treatments to the fetus in vivo. A low-AGTH-condition was given to the fetus by administrating Dexamethasone through its mother, or directly into the subcutaneous tissue of the fetus, or by decapitation, brain aspiration or hypophysectomy. When the fetus was given the low-ACTH-condition for the last 5 days or more, the hypoplastic adrenal cortex developed specifically. It had nearly normal zona glomerulosa (ZG), and poorly differentiated zona fasciculo-reticularis (ZF-R) without differentiated ZF-R. The observing day was settled at 21 1/2 days old. The shorter the period of low-ACTH-condition was, the more thickened the differentiated zone (ZF-R) grew. On the contrary, the poorly differentiated layer became thinner in proportion to the period of low-ACTH-condition. The poorly differentiated cortical cell had ACTH-reactivity. It seems that the development and tissue differentiation of the ZF-R depend on fetal own ACTH, and poorly differentiated cortical cells appear below the ZG, and differentiate by ACTH and were gradually pushed inside. The zona glomerulosa develops and differentiates without dependence of ACTH. ACTA PATH. JAP. 27: 759-773, 1977.

Differentiation of the fetal adrenal cortex of rats--its experimental observation in vivo.

The effect caused by the double condition of potassium loading (K loading) and simultaneous sodium restriction (Na restriction) on the glomerular zone of rats is reported. After 2-week-diet of K loading and simultaneous Na restriction an increase of width of glomerular zone and decreases and micronization of fat granules were seen. Enzymic activity (glucose-6-phosphate dehydrogenase, steroid 3beta-ol-dehydrogenase) was increased. After 3-week-diet of the same condition the width of glomerular zone became 1/4 to 1/5 of the whole cortex. The cells in the glomerular zone demonstrated a trabecular arrangement. Ultrastructurally, hypertrophy of cells became marked and the size of cell was about 1.5 times that of normal cells. Dense body increased in number and became irregular in shape. In the widened cytoplasm, smooth endoplasmic reticulum and Golgi apparatus were well developed with numerous coated vesicles. Changes of mitochondria such as increase in number, transformation into round shape and vesicular cristae were characteristic. The severity of these changes was proportional to the duration of K loading and simultaneous Na restriction. After 8-week-diet the increase of large-sized lipid vacuole and dense body, and intramitochondrial deposition were observed in parallel with the above-mentioned changes. The changes observed in this study appeared earlier and stronger than those in the single-conditioned group of only K loading or Na restriction. The cause of these changes were considered to be a result of accelerated function of the glomerular cells.

The effect caused by the double condition of potassium loading and simultaneous sodium restriction on the glomerular zone of rats

Intracortical nodules in the zona fasciculata of rat adrenal glands were studied electron microscopically and histochemically. The nodules were classified into the following three types. A) Hyperplastic small cell type having numerous elongated mitochondria with vesicular cristae. Alkaline phosphatase activity was increased in this type of nodule. B) Hypertrophic large cell type having well developed smooth-surfaced endoplasmic reticulum, and occasionally forming a characteristic feature of fenestrated cisterna. Histochemical activity of steroid 3/3-ol dehydrogenase was increased. These morphological appearances suggest that this type of nodule has a greater capacity for steroid synthesis. C) Lipid droplet type having many mitochondria containing lamellar cristae and intramltochondrial deposits often found near large lipid vacuoles. The activity of secondary alcohol dehydrogenase was generally increased.



Structural and cellular relationships among these three types of nodule and the pathogenesis of cortical adenomatous nodule were also discussed.

Pathology of intracortical nodules in rat adrenal glands, especially on their fine‐structure

Pigmented lipid histiocytes (PLH) of chronic granulomatous disease (CGD) were examined by histochemistry and electron microscopy. The yellowish brown pigments were stainable with Sudan III and IV even in paraffin sections, and the sudanophilia was kept after oxidation with peracetic acid followed by methylation. In addition, the granules were positive to Gomori's chromium hematoxylin stain, 0.02% Nile blue sulfate stain and leuco-malachite green stain. Ultrastructural observation showed numerous intracytoplasmic granules in variable shapes and sizes measuring up to 4.8μ in diameter, with various electron densities. From these results, the pigment in PLH of CGD is comparable to a ceroid-like substance. The nature of the pigment and the pathogenesis of PLH are also discussed.

Hajime Sugihara

Papers

Neuro-Behçet's syndrome: report of two autopsy cases.

Differentiation of the fetal adrenal cortex of rats--its experimental observation in vivo.

The effect caused by the double condition of potassium loading and simultaneous sodium restriction on the glomerular zone of rats

Pathology of intracortical nodules in rat adrenal glands, especially on their fine‐structure

Histochemical and ultrastructural observation of the pigment in pigmented lipid histiocytes of chronic granulomatous disease