Biomedical subjects

F Garzuly

Publications and source records attributed to F Garzuly.

At least 19 recordsLinked to original sources

PubMed2002

Cutaneous lymphatic amyloid deposits in "Hungarian-type" familial transthyretin amyloidosis: a case report.

Multiple transthyretin (TTR) mutations have recently been identified and implicated in the development of familial systemic amyloidoses, but early diagnosis of these disorders is still largely unresolved. We investigated the presence and tissue distribution of TTR-derived amyloid in skin biopsies of a 59-year-old woman carrying the "Hungarian-type" mutation of TTR (Asp18Gly). Clinical symptoms involved severe central nervous system dysfunction without signs of polyneuropathy, also referred to as the "central form" of TTR-related systemic amyloidosis. Skin biopsy was also evaluated as a tool in order to diagnose this type of TTR amyloidosis. Biopsy samples were collected from the infra-axillary region. Light microscopy using Congo red and polarized light was used to diagnose amyloid deposits. Subsequently, electron microscopic analysis was performed to correlate the amyloid deposits with vicinal dermal structures. The amyloid class was determined by means of immunocytochemistry. TTR amyloid was primarily localized to lymphatic microvessels in the present case, whereas arterioles were devoid of TTR amyloid deposits. In addition, the well-known association of TTR amyloid with neural structures along the erector pilorum and around the sebaceous and serosal (sweat) glands was also evident. Electron microscopic analysis of amyloid deposits revealed characteristic amyloid fibrils that were irregular in shape, and exhibited a heterogeneous density and a random deposition pattern. Immunocytochemistry confirmed the cutaneous accumulation of TTR amyloid. In conclusion, amyloid deposits were abundantly present in the skin of a patient with "Hungarian-type" TTR amyloidosis; skin biopsy seems to be appropriate for the diagnosis of this disorder. We showed that besides the erector pilorum, sweat glands and nerve terminals, lymphatic microvessels are also severely infiltrated by TTR amyloid. Whether these pathological alterations can exclusively be found in "Hungarian-type" TTR amyloidosis should still be investigated. If such changes are not specific for the Asp18Gly mutation, they may be considered as diagnostic markers for "central" TTR amyloid disorders.

Amyloidosis↗

PubMed1996

[Clinical characteristics of Hungarian-type familial meningo-cerebrovascular amyloidosis].

Amyloid deposits of the CNS caused clinical symptoms in four members of a Hungarian family. Histological investigations revealed a systemic disease, immunohistologically the deposited material was a transthyretin variant, DNA analysis showed a new transthyretin mutation (TTRAsp 18Gly). The disease--named meningocerebrovascular amyloidosis, Hungarian type--is inherited dominantly like other already known familial amyloidoses caused by transthyretin variants, however it does not cause the usual familial polyneuropathy but symptoms similar to those of the rare oculoleptomeningeal amyloidosis. The aim of the present study is to point to differential diagnosis. Its complaints, neurological signs and clinical findings which may be suspect of atypical migraine, brain tumour, chronic leptomeningitis or herpes encephalitis, multiple sclerosis and Parkinson disease are analysed and compared with those of other known types of familial amyloidoses. Attention is drawn to symmetrical calcification on CT scans. Skin biopsy may help the diagnosis. At present, therapy is only symptomatic.

Amyloidosis↗

PubMed1996

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↗

PubMed1996

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↗

PubMed1994

[Pathological features of neuroleukemia. Changes and lessons].

Between 1971 and 1992 neuropathological examinations were performed in 316 patients having died of leukaemia. Among them 73 had acute lymphoid leukaemia, 134 acute myeloid leukaemia, 49 chronic lymphoid leukaemia and 60 chronic myeloid leukaemia. Meningeal leukaemia, which had been a frequent pathological complication at the beginning of the examination period, later had become rarer. The study made it possible to define further neurologic complications, the characteristic neuropathological changes of the different types and some subtypes of leukaemia and to draw clinical consequences. The incidence of cerebral "leukaemic nodules" was twelve times higher in the myeloid than in the lymphoid leukaemias, this may be the explanation for the fact that central nervous system haemorrhage was more frequent in the myeloid types. Subdural haematoma can primarily be expected in acute myeloid leukaemia. The neuropathologic features of chronic lymphoid leukaemia were particular, as no "leukaemic nodules" developed, and meningeal leukaemia was a rare event; at the same time, it was related with the highest incidence of infiltration of the dura mater and the sciatic nerve.

Adolescent↗

PubMed1993

[Hypernephroma and associated AL-amyloidosis with polyneuropathy in monoclonal gammopathy].

Malignant neoplasms may have secondary (reactive, AA), amyloidosis as a sequel. Among carcinomas, this is most frequent with hypernephroma. We report a 60-year-old male patient with progressive polyneuropathy and monoclonal gammopathy of the kappa type. A renal tumor was histologically diagnosed as hypernephroma at nephrectomy. The patient did not improve postoperatively and died three and a half months later from pulmonary embolism. Autopsy revealed a systemic amyloidosis, predominantly with prominent deposits in peripheral nerves. Immunohistochemical staining demonstrated the amyloidosis as of the primary (AL) type, rather than of the expected AA type. A plasmocytoma was not detected, either clinically or at autopsy. We assume here a coincidental rather than causal connection between the hypernephroma and the monoclonal gammopathy with AL amyloid and the neuropathy.

Amyloid↗

PubMed1986