Phenotypic variation in Creutzfeldt-Jakob disease, May 31 and June 1, 1996, Vienna, Austria.
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Animals↗
Biomedical subjects
H Budka
Publications and source records attributed to H Budka.
Creutzfeldt-Jakob disease in Austria.
Between 1969 and 30 September 1995, 79 Austrian patients had Creutzfeldt-Jakob disease (CJD) diagnosed neuropathologically by necropsy or biopsy. The annual incidence has significantly increased in recent years (average 0.18 per million in 1969-85, and 0.67 per million in 1986-94; estimate for 1995: 1.5 per million). Also, the percentage of patients with CJD over 70 years at death increased significantly until 1989 but is since in decline. There is no regional clustering, familial occurrence, or recognised iatrogenic risk. One patient had a 10 year history of intramuscular injection of purified bovine RNA preparation (Regeneresen) from various organs including the brian. The ages at death are symmetrically distributed around the median of 64 years. The median duration of disease is four months. Most patients (76%) died within six months of onset. Retrospectively, 86% of patients fulfilled clinical criteria of probable or possible CJD. Neuropathology showed the classic triad of spongiform change, astrogliosis, and neuronal loss in most cases. Two cases did not show unequivocal tissue alterations, but anti-PrP immunocytochemistry detected PrP deposits also in these cases. It is concluded that the recent rise in incidence of CJD in Austria most likely reflects increased awareness and diagnosis of CJD rather than a real increase. As bovine spongiform encephalopathy (BSE) has not been reported in Austria, the data do not support a link between a rise in incidence of sporadic CJD and BSE.
Adolescent↗
Subacute measles virus encephalitis: a new and fatal opportunistic infection in a patient with AIDS.
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AIDS-Related Opportunistic Infections↗
Familial meningocerebrovascular amyloidosis, Hungarian type, with mutant transthyretin (TTR Asp18Gly)
Amyloid deposits in leptomeningeal vessels, subarachnoid, subpial, and subependymal cerebrospinal regions, spinal ganglia, peripheral nerves, and some internal organs (predominantly heart and kidney) characterize a dominantly inherited disease in a Hungarian family. We found four definitely and three probably affected members in this family of 56 persons in four generations. Clinical features in all definitely diseased patients include disturbance of memory, psychomotor deceleration, ataxia, and hearing loss. In most patients there was temporary disorientation, migraine-like headache with vomiting, and tremor. Some patients had nystagmus, pyramidal signs with spastic paraparesis, hallucinations, urinary retention, and obstipation. Single patients had facial tics and sleep disorders. Progressive visual disturbance and clinically manifest polyneuropathy were absent. CSF protein was markedly elevated in all patients. CT showed characteristic symmetric calcification along the sylvian fissure; MRI after contrast administration showed prominent enhancement at the surface of the sylvian fissures, brainstem, and cerebellum. Autopsy data was available in three definitely affected patients and in one unaffected family member. Immunohistochemistry identified the amyloid deposits as of the AF (transthyretin, TTR) type; DNA studies revealed a novel TTR missense mutation at codon 18 (TTR Asp18Gly). According to clinical features, pathologic alterations, and molecular studies, this disease is a novel type of systemic familial amyloidosis with disease manifestation clinically restricted to the CNS. It is similar to the oculoleptomeningeal amyloidoses but can be clinically diagnosed by characteristic CTs and the absence of progressive visual impairment.
Adult↗
Meningocerebrovascular amyloidosis associated with a novel transthyretin mis-sense mutation at codon 18 (TTRD 18G)
We describe a novel transthyretin mutation at codon 18 where Asp is replaced by Gly (D18G) in a Hungarian kindred. This mutation is associated with meningocerebrovascular amyloidosis, producing dementia, ataxia, and spasticity. Fifty different transthyretin mutations are related to amyloid deposition, typically producing a peripheral neuropathy or cardiac dysfunction. These symptoms are absent in this family. Up to now, amyloid-beta (A beta), cystatin C, and prion proteins have been known to be deposited as amyloid in the brain, leading to stroke or dementia. With this report we establish that transthyretin amyloid deposition can also produce central nervous system dysfunction as the major clinical symptom.
Amino Acid Sequence↗
[Consensus report: tissue handling in suspected Creutzfeldt-Jakob disease and other spongiform encephalopathies (prion diseases) in the human. European Union Biomed-1 Concerted Action].
Despite many sensational and intimidating reports in the mass media, transmissible spongiform encephalopathies (prion diseases) are not contagious in the usual sense. Successful transmission requires both specific material (an affected individual's tissue, from or adjacent to CNS) and specific modes (mainly penetrating contact with the recipient). Nevertheless, specific safety precautions are mandatory to avoid accidental transmission and to decontaminate any infectivity. The autopsy is essential for definite diagnosis of these disorders. Recommendations are given here for safe performance of the autopsy, for neuropathology service and appropriate decontamination; they are based on the current literature and on precautions taken in most laboratories experienced in handling tissue from transmissible spongiform encephalopathies. In essence, special care must be taken to avoid penetrating wounds, possible contamination should be kept to a minimum, and potentially infectious material must be adequately decontaminated by specific means. The full English text of this Consensus Report was published in Brain Pathology 5: 319-322 (1995).
Autopsy↗
Repermeation of partially embolized cerebral arteriovenous malformations: a clinical, radiologic, and histologic study.
PURPOSE: To describe the pattern and time course of embolization-related tissue lesions and repermeation of the intranidal cast after endovascular embolization of cerebral arteriovenous malformations (AVMs) with N-butyl cyanoacrylate (NBCA). METHODS: We retrospectively reviewed the records of 26 patients who were treated by endovascular embolization with NBCA and subsequent surgical extirpation to look for embolization-related tissue lesions and repermeation of the cast. A residual flow through the malformation was identified on preoperative angiograms in every case. RESULTS: Pattern and time course of embolization-related tissue lesions were typical. Until 3 months after embolization, repermeation of embolized structures did not occur. In contrast, repermeation was found in every patient who had surgery later than 3 months after the first embolization (n = 13; 50%). In these cases, histologic examination of the resected nidus disclosed capillary structures inside the lumen of embolized vessels. Capillaries were traced immunohistochemically with antibodies against membrane-bound factor VIII. No parameter other than the interval between the first embolization and surgery was found to relate to the repermeation of the cast. CONCLUSION: Intranidal recapillarization can occur later than 3 months after the first embolization with NBCA if total and solid casting of the nidus was not accomplished.
Adolescent↗
[Spinal pathology in spinal muscular atrophy in comparison with amyotrophic lateral sclerosis].
We analyze neuronal cytopathology and secondary reactions in spinal-muscular atrophy (SMA) in comparison with amyotrophic lateral sclerosis (ALS). In a series of SMA and ALS cases, immunohistochemistry was performed on spinal cord sections for neuronal, astroglial and microglial antigens, ubiquitin and tau proteins. Swollen motoneurons staining for phosphorylated neurofilament proteins are seen in most SMA but few ALS cases. Ubiquitinated inclusions are found only in ALS. In SMA, glial bundles are prominent in anterior roots, to lesser extent in posterior roots. In ALS, glial bundles are seen only in some cases. While basic histopathologies are similar in both types of motor neurone diseases, neuronal cytoskeletal pathology is more prominent in SMA, possibly reflecting a more acute degenerative process. The presence of axon spheroids and glial bundles also in posterior horns/roots of both types of motor neurone disease suggests spread of degenerative pathology beyond the motor system.
Amyotrophic Lateral Sclerosis↗
[Sporadic juvenile amyotrophic lateral sclerosis with neuronal basophil inclusion bodies--a nosologic entity?].
Among the very few cases of juvenile sporadic amyotrophic lateral sclerosis (ALS), 6 cases with neuronal basophilic inclusion bodies (BI) and clinical features uncommon to "classical" adult sporadic ALS have been reported. We present here two further cases and review the relevant literature. There are clinical and neuropathological similarities of systemic degeneration between juvenile cases with or without BI and juvenile and adult sporadic ALS when the latter is allowed to run a protracted course in patients on respirators. Because of overlapping topology and neuronal cytoskeletal pathology, the nosologic distinction within the ALS spectrum is questionable.
Adult↗
[Multifocal motor neuropathy with conduction block--a clinico-neuropathologic case report].
Descriptions on patients with multifocal motor neuropathy with conduction block (MMNCB), including histology, nerve fiber teasing and electron microscopy on nerve biopsy, are rare. We report a 64-year old female patient with progredient weakness of the upper extremities without sensory deficit. Electrophysiology shows conduction blocks up to 80% in several examined motor nerves. A biopsy of the sensory sural nerve reveals features of a mixed axonal and de- and remyelinating neuropathy. Thus sural nerve biopsy contributes here significantly to differential diagnosis and supports an immune mediated pathogenesis of MMNCB.
Amyotrophic Lateral Sclerosis↗
Clinical, radiological and histological presentations of dysembryoplastic neuroepithelial tumors (DNT). Report of two cases.
Dysembryoplastic neuroepithelial tumor (DNT) is a recently described rare brain neoplasm with characteristic clinical and morphological features and favorable prognosis. We report here two cases of DNT. The first concerned a 12 years old girl who presented complex seizures preceded by acoustic aura (melodies). Computed tomography revealed a hypodense tumor measuring 2 x 2.5 cm in diameter, located paracortically in the left temporal lobe. The second tumor was removed from a 21-year-old man with partial complex seizures. Nine years earlier patient underwent neurosurgery with partial removal of the tumor The tumor's histopathologic diagnosis is unfortunately lacking. Computed and magnetic resonance imaging showed a mass occupying the cortex and paracortical areas of the anterior pole of the temporal lobe. Histologically, both tumors consisted of small, S-100 protein immunopositive oligodendrocyte-like cells (OLCs) arranged between synaptophysin- and, to a lesser degree, NFP-immunopositive axons (glioneuronal element). In the second case, an area of pilocytic astrocytoma-like appearance was also found, these cells were immunopositive for GFAP. The present study provides clinical, radiological and histological data, which may be helpful in differential diagnosis of this newly recognised brain tumor.
Adult↗
Suprasellar meningioma with expression of glial fibrillary acidic protein: a peculiar variant.
A 24-year-old female presented with a 3-year history of a suprasellar and intraventricular solid midline process measuring about 3 x 4 cm. At surgery, this tumour was sharply delineated and of stone-like firmness and was removed completely. Histology suggested meningioma, featuring nests and cords of epithelium-like cells with prominent cytoplasm amidst abundant fibrous stroma with prominent lymphoplasmocellular infiltration. Immunocytochemically, the tumour cells expressed vimentin, S-100 protein, epithelial membrane antigen, cytokeratins, and most surprisingly, glial fibrillary acidic protein (GFAP). Ultrastructural investigation revealed abundant intermediate filaments and occasionally dense secretory granules in tumour cells with short, finger-like cytoplasmic processes joined by very rare small, but well-developed desmosomes. This tumour most likely represents a peculiar variant of meningioma with prominent production of GFAP, as previously described [Budka H (1986) Acta Neuropathol (Berl) 72: 43-54].
Adult↗
Immunohistochemical study of apolipoprotein E in human cerebrovascular white matter lesions.
In the brains of ine cases with cerebrovascular disease, one with mixed dementia, one with amyloid angiopathy and two non-neurological controls, we found three cases with focal accumulation of apolipoprotein E (apo-E) in dystrophic axons and accompanying macrophages. Since amyloid precursor protein (APP) and chromogranin A (CgA) accumulate after axonal damages, and are sensitive markers of the white matter lesions, the regional distribution of apo-E was compared to that of APP and CgA. apo-E-immunoreactive axons were present in the periphery of an infarction with neighboring macrophages, but not in mild white matter lesions that contained APP- or CgA-immunoreactive fiber bundles. The results suggest a role of apo-E in recycling cholesterol and other membrane components via macrophages into remodeling neurites in the brain, but this phenomenon is restricted to the periphery of infarction and may be less prominent than in the peripheral nervous system.
Aged↗
Trilobar holoprosencephaly ("triprosencephaly"): a unique type of cerebral malformation.
Little is known about the neuropathology of the median facial cleft syndrome, which presents as a combination of a wide range of teratological manifestations. We report a unique type of cerebral malformation combined with the median facial cleft syndrome in a 7-day-old female infant with malformations of toes and fingers, hypertelorism and a median cleft nose, as well as a frontally protruding, dorsomedian hornlike cele. At autopsy, the cranium presented facial clefts and bony defects, resulting in partitioning of the anterior cranial fossa into three compartments. The brain had malformative features of lobar holoprosencephaly combined with tripartition of frontal lobes, including an encephalomeningocystocele originating from a right accessory frontal lobe.
Abnormalities, Multiple↗
Diffuse Lewy body disease as substrate of primary lateral sclerosis.
We describe the case of a 40-year-old male patient who had presented clinically as primary lateral sclerosis for the past 10 years and neuropathologically as diffuse Lewy body disease (DLBD). Neuropathology demonstrated DLBD as an almost ubiquitous disorder of the neuronal cytoskeleton.
Adult↗
Diagnostic value of stereotactic biopsy of cerebral lesions in patients with AIDS.
A neurological complication occurs in 40-60% of HIV infected patients during the course of the disease. In 10-20% the neurological complication is the first manifestation of the HIV infection. A reliable neuropathological diagnosis is a prerequisite for a specifically selected treatment. While modern computer-assisted imaging techniques, such as computed tomography or magnetic resonance imaging, do possess a high sensitivity, they do not as a rule permit an unambiguous diagnosis. Between October 1989 and July 1994 we biopsied 38 HIV infected patients stereotactically. The indication for the biopsy was determined by having radiologically detectable lesions with no regression tendency in patients under antitoxoplasmosis therapy. In 89% an unambiguous diagnosis was made based on the biopsy; 11% of the biopsies were not diagnostic. For the most part, toxoplasmosis (31%) and progressive multifocal leucoencephalopathy (29%) were involved. 18% of the patients suffered from a non-Hodgkin lymphoma. The foci were primarily frontal (47%), parietal (21%) or localised in the basal ganglia area (11%). The result of the biopsy led to a change in treatment for 52% of the patients. Morbidity and mortality of the operation were 0%. The results or our research series are similar to other groups. It was shown that stereotactic brain biopsy is a safe and effective method for establishing a sound basis for treating the frequently life-threatening cerebral complications of AIDS.
Acquired Immunodeficiency Syndrome↗
Neuroaxonal dystrophy in experimental Creutzfeldt-Jakob disease: electron microscopical and immunohistochemical demonstration of neurofilament accumulations within affected neurites.
Neuroaxonal dystrophy is a feature of neuronal degeneration encountered in all subacute spongiform "virus" encephalopathies, including scrapie and Creutzfeldt-Jakob disease (CJD). By immunohistochemical techniques, the accumulation of 200 kDa neurofilament protein was demonstrated in affected neurites in murine CJD. These neurites exhibited the ultrastructural features of dystrophic neurites encountered in other neurodegenerative disorders, particularly Alzheimer's disease. These findings support the hypothesis that impairment of slow axoplasmic transport is a common pathogenetic mechanism for CJD and many other neurodegenerative conditions.
Animals↗
Tissue handling in suspected Creutzfeldt-Jakob disease (CJD) and other human spongiform encephalopathies (prion diseases)
Despite many sensational and intimidating reports in the mass media, transmissible spongiform encephalopathies (prion disease) are not contagious in the usual sense. Successful transmission requires both specific material (an affected individual's tissue, from or adjacent to CNS) and specific modes (mainly penetrating contact with the recipient). Nevertheless, specific safety precautions are mandatory to avoid accidental transmission and to decontaminate any infectivity. Autopsy is essential for definite diagnosis of these disorders. Recommendations are given here for performance of the autopsy, for neuropathology service and appropriate decontamination; they are based on the current literature and on precautions taken in most laboratories with experience in handling tissue from transmissible spongiform encephalopathies. In particular, special care must be taken to avoid penetrating wounds, possible contamination should be kept to a minimum, and potential infectious material must be adequately decontaminated by specific means.
Autopsy↗