Early olfactory involvement in Alzheimer's disease.

BACKGROUND: In Alzheimer's disease (AD) the olfactory system, including the olfactory bulb, a limbic paleocortex is severely damaged. The occurrence of early olfactory deficits and the presence of senile plaques and neurofibrillary tangles in olfactory bulb were reported previously by a few authors. The goal of the present study was to analyze the occurrence of AD-type degenerative changes in the peripheral part of the olfactory system and to answer the question whether the frequency and severity of changes in the olfactory bulb and tract are associated with those of the cerebral cortex in AD. MATERIAL AND METHODS: In 110 autopsy cases several cortical areas and the olfactory bulb and tract were analyzed using histo- and immunohistochemical techniques. Based on a semiquantitative analysis of cortical senile plaques, neurofibrillary tangles and curly fibers, the 110 cases were divided into four groups: 19 cases with severe (definite AD), 14 cases with moderate, 58 cases with discrete and 19 control cases without AD-type cortical changes. RESULTS: The number of cases with olfactory involvement was very high, more than 84% in the three groups with cortical AD-type lesions. Degenerative olfactory changes were present in all 19 definite AD cases, and in two of the 19 controls. The statistical analysis showed a significant association between the peripheral olfactory and cortical degenerative changes with respect to their frequency and severity (P < 0.001). Neurofibrillary tangles and neuropil threads appear in the olfactory system as early as in entorhinal cortex. CONCLUSION: The results indicate a close relationship between the olfactory and cortical degenerative changes and indicate that the involvement of the olfactory bulb and tract is one of the earliest events in the degenerative process of the central nervous system in AD.

[Evaluation of combined neurosurgical and trans-facial excision of extensive rhinosinus tumors infiltrating the anterior skull base]. / Evaluation de l'exérèse combinée neurochirurgicale et transfaciale des tumeurs rhino-sinusales extensives infiltrant la base antérieure du crâne.

Rhino-sinusal tumors are rare, representing approximately 0.3% of all cancers and 3% of tumors of the upper respiratory and digestive tracts. In cases in which the tumor has infiltrated the anterior cranial base, the treatment of choice is a surgical resection by combined neurosurgical and transfacial approach giving the best possible exposition for the excision. The resection is associated with various reconstruction techniques according to the extent of the defect. Sixteen patients with rhino-sinusal tumors extending to the anterior cerebral cavity were operated at the ENT clinic of the CHUV in Lausanne between 1977 and 1997. The transfacial and neurosurgical combined approach is rarely curative (30% 5 years survival rate, 80% local recurrence during follow-up), but is still justified, given that its disabling side-effects are scarce. It offers an acceptable quality of life and prevents complications inherent to the natural development of tumors. Pre- or postoperative radio- and chemotherapy, as well as skull base reconstructions using bone grafts or a micro-anastomosed flap give rise to complications which worsen significantly the overall prognosis and should therefore be avoided as much as possible. Still, this heavy surgery remains indicated, because it prevents the numerous complications of the natural course of the disease and offers an acceptable quality of life with only few side-effects.

Alzheimer disease: curly fibers and tangles in organs other than brain.

The filamentous brain lesions that define Alzheimer disease (AD) consist of senile plaques and neurofibrillary tangles. Undulated pathological filaments--curly fibers or neuropil threads--also occur in the neuropil. Beta-amyloid precursor proteins are synthesized by many cells outside the central nervous system and recently, deposition of beta-amyloid-protein was reported to occur in non-neuronal tissues. In addition, increasing data claim the importance of chronic inflammation in the pathogenesis of AD. These observations suggest that AD may be a widespread systemic disorder. Here we report that pathological argyrophilic filaments with histochemical properties of amyloid showing striking morphological similarity to curly fibers and/or tangles accumulate not only in ependymal layer and in epithelial cells of choroid plexus, but also in several other organs (e.g. liver, pancreas, ovary, testis, thyroid) in AD. The ependyma, choroid plexus, and various organs of 39 autopsy cases were analyzed. In search of curly fiber and tangle-like changes in organs other than brain, 395 blocks from 21 different tissues of 24 AD cases, 5 cases with discrete or moderate AD-type changes, and 10 control cases were investigated. We found in non-neuronal cells "curly fibers" or "tangles" immunoreactive with antibodies to P component, Tau-protein, ubiquitin, fibronectin, and Apolipoprotein-E, but lacking immunoreactivity with antibodies to neurofilament proteins. Ultrastructurally they consist of densely packed straight and paired helical filaments and closely resemble neurofibrillary tangles and neuropil threads. These observations indicate that the formation of "curly fibers" and "tangles" is not unique to the central nervous system. The results suggest that AD might be a systemic disorder or that similar fibrillary changes to tangles and curly fibers may also be associated with other amyloidosis than beta-amyloidosis. Further investigations are necessary to understand the pathogenetic interest of these fibrillary changes outside the CNS.

Curly fiber and tangle-like inclusions in the ependyma and choroid plexus--a pathogenetic relationship with the cortical Alzheimer-type changes?

The question of whether thread- and tangle-like inclusions of the choroid plexus (known as Biondi inclusions) are related to the cortical lesions in Alzheimer disease (AD) has been debated for almost a century, yet remains unanswered. Recently beta-amyloid protein was biochemically isolated from the plexus, indicating a possible pathogenetic relationship between the degenerative changes of the cerebral cortex and those of the plexus. The goal of the present study was to analyze whether or not a significant correlation exists between the occurrence of the cortical AD-type changes and those in the ependyma and choroid plexus. In 292 consecutive autopsy cases several cortical areas, the ependyma, and the choroid plexus were analyzed to look for AD-type changes and Biondi inclusions using histochemical staining techniques and immunohistochemistry. A semiquantitative analysis of the density of cortical AD-type changes showed that of the 292 cases, 63 had severe cortical changes, 23 moderate changes, and 142 discrete changes. In 64 cases no plaques or neurofibrillary tangles were found. The number of cases with thread- and tangle-like elements in the plexus and ependyma was more than 96% in the 3 groups with cortical AD-type lesions, but low in the group without AD-type cortical changes (19%). The pathological argyrophilic filaments accumulating in the ependymal layer and plexus had histochemical properties of amyloid and were immunoreactive with antibodies to P component, ubiquitin, fibronectin and Tau protein. They did not react with antibodies to neurofilament proteins. Ultrastructurally, they consisted of densely packed straight and paired helical filaments and closely resembled neurofibrillary tangles and neuropil threads. The highly significant correlation (chi2, p = 0.001; R = 0.85) between the occurrence of AD-type changes in the cortex and those in ependyma and plexus suggests a pathogenetic relationship.