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Clinical Neuroscience

JULY 30, 2019

Cerebral cavernous malformation type 1 with retinal blood vessel tortuosity and KRIT1 gene mutation

KALMÁR Tibor, MARÓTI Zoltán, VADVÁRI Árpád, HALMOSI Ágnes, KÁLOVITS Ferenc, KÁLMÁN Bernadette

Cerebral cavernous malformations (CCMs) represent a relatively rare and heterogeneous clinical entity with mutations identified in three genes. Both sporadic and familial forms have been reported. We present a young female patient with episodic paresthesia and headaches, but without acute neurological deficits. Her mother had a hemorrhaged cavernoma surgically removed 21 years ago. Cranial magnetic resonance imaging revealed multiple cavernous malformations in the size of a few millimeters and the ophthalmologic exam detected retinal blood vessel tortuosity in the proband. Targeted exome sequencing analysis identified a nonsense mutation in exon 16 of the KRIT1 gene, which resulted in a premature stop codon and a truncated protein underlying the abnormal development of cerebral and retinal blood vessels. This mutation with pathogenic significance has been reported before. Our case points to the importance of a thorough clinical and molecular work up despite the uncertain neurological complaints, since life style recommendations, imaging monitoring and genetic counseling may have major significance in the long term health of the patient.

Clinical Neuroscience

JULY 30, 2016

[Transthyretin familial amyloid polyneuropathy - three Hungarian cases with rare mutations (His88Arg and Phe33Leu)]

CSILLIK Anita, POZSONYI Zoltán, SOÓS Krisztina, BALOGH István, BODÓ Imre, ARÁNYI Zsuzsanna

[Introduction - Transthyretin familial amyloid polyneuropathy is a rare autosomal dominant progressive systemic disesase of adults caused by endoneural amyloid deposition due to point mutations of the transthyretin gene. It is the most severe form among hereditary polyneuropathies, being fatal within 10 years if left untreated. The disease is underdiagnosed, the late onset forms (above the age of 50) being probably more widespread than previously thought. Early diagnosis is essential as the early introduction of causal therapy (tafamidis) slows progression and prolongs survival. Patients - We report here three non-related Hungarian cases of transthyretin familial amyloid polyneuropathy with non- Val30Met mutations (His88Arg in two cases, Phe33Leu in one case). They were all characterized by late-onset, progressive, length-dependent, axonal, sensorimotor polyneuropathy and the simultaneous presentation of severe restrictive cardiomyopathy. In all three cases, clinical and electrophysiological signs of myopathy were also present, suggesting the involvement of skeletal muscles as well. In two cases, high resolution ultrasound of the peripheral nerves was also performed, which showed segmental structural alterations (change or loss of fascicular structure) and some increase of echogenicity of the interfascicular epineurium, without substantial enlargement of the nerves. Conclusion - In Hungary, mainly the rare, non-Val30Met mutation forms of transthyretin familial amyloid polyneuropathy are encountered, as in our cases. As opposed to the Val30Met forms, these mutations are characterized by late onset and simultaneous presentation of severe cardiomyopathy. Our report highlights the importance of considering transthyretin familial amyloid polyneuropathy in the differential diagnosis of late-onset, progressive, axonal polyneuropathies of unknown etiology, particularly if associated with cardiac disease.]

Clinical Oncology

DECEMBER 05, 2014

[Bone metastases - Current treatment strategy]

BOÉR Katalin, NÉMETH Zsuzsanna

[Bone is the most common site of metastatic disease in many solid tumours, mainly in breast, prostate and lung cancer. Patients with bone metastases are at risk for skeletal-related events such as bone pain, pathological fractures requiring surgery and/or radiation to bone lesions, hypercalcemia, and spinal cord compression. Skeletal-related events are major source of morbidity for cancer patients and may be associated with negative impact on quality of life and survival. Bisphosphonates inhibit osteoclast function and are widely used in the treatment of malignant bone disease, as preventive therapy against skeletal-related events. Recently, the NF-κappa B-ligand (RANKL)-mediated osteoclast activity and this pathway in bone metabolism became a prime target for the treatment of bone metastases. The fi rst drug targeting the RANK-RANKL pathway is denosumab, a fully monoclonal human antibody which binds to RANKL and inhibits osteoclast activity. Nowadays optimal treatment of bone metastases requires multidisciplinary management of patients including the administration of bone-modifying agents such bisphosphonates or denosumab. The use of bone-targeted agents is a valuable additional treatment in the fi ght against bone metastases and multiple, randomised trials have demonstrated the effectivity of these drugs in reducing skeletal morbidity caused by advanced cancer.]

Lege Artis Medicinae

FEBRUARY 05, 2016

[Effect of rosuvastatin therapy’s introduction on lipid levels and on proportion of target values reaching in patients with familial hypercholesterolemia and familiarity]

SZTANEK Ferenc

[Familial hypercholesterolemia (FH) is a genetically heterogeneous disorders characterized by very high total cholesterol and low-density lipoprotein (LDL) cholesterol levels, and it accelerates the development of atherosclerosis and early cardiovascular disease. FH is most commonly caused by mutations in low-density lipoprotein receptor (LDLR) or apolipoprotein B-100 (APOB) genes. In rest of the cases the mutation is in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene. Previous studies have shown that rosuvastatin significantly reduces major cardiovascular events in high risk patients. The goal of our study was to investigate the lipid-altering efficacy of simvastatin or atorvastatin therapy compared with high-intensity rosuvastatin therapy in patients with FH and familiarity. Recent work has demonstrated the efficacy of high-intensity rosuvastatin therapy in enabling high-risk and very high-risk patients in lowering significantly plasma levels of total and LDL-cholesterol, which can subtantially affect major cardiovascular events in familial hypercholesterolemia.]

Clinical Neuroscience

DECEMBER 20, 2008

[Convulsions in neonatal period and infancy with rare etiology (neurogenetic disease)]

NAGY Andrea, SZEVER Zsuzsa, KORMOS Zsuzsa, SZÉKELY Emőke, TÓTH EDIT, SMIDÉLIUSZ Lajos, HORVÁTH Rita, KARCAGI Vera, SCHULER Ágnes, JÁVORSZKY Eszter

[Authors summerized the etiology of convulsions in neonatal period and infancy (hypoxy, intracranial hemorrhage, infections of central nervous system, metabolic background, chromosomal abnormalities, brain developmental abnormalities, benign neonatal convulsions, benign neonatal familial convulsions, drug withdrawal, inborn error of metabolism). They suggest screening examinations after convulsion, summerized the basic princpile of tandem examination and review a proposal at suspicion of inborn error of enzym defects (aminoacidemias, defects of fatty acid oxydation, organic acidemias). They present case history of two patients suffered in extraordinary inborn error of enzym defect (SCO2 gene mutation, propionic acidemia). Diagnosis originated in Heim Pál Hospital (settlement Madarász Hospital) with a Hungarian and international cooperation.]

Hungarian Radiology

DECEMBER 20, 2007

[Sarcoidosis involving liver and spleen, and with hypercalcemia]

TÓTH Mónika, WENINGER Csaba, MORÓ Zsuzsanna, SZOMOR Árpád

[INTRODUCTION - Sarcoidosis is a relatively common multisystemic disorder. Chest involvement is most frequent, but any organ can be involved. In case of abdominal lesions the suspicion of sarcoidosis rarely arises. CASE REPORT - A 53-year old female patient with a history of crural pain unresponsive to medications and weight loss of unknown origin was sent to the internist. Hypercalcemia and bone pain suggested multiple myeloma, however, this diagnosis could not be confirmed. Chest X-ray examination was negative. Splenomegaly and multiple hypodens splenic and hepatic lesions were detected by ultrasound and abdominal computed tomography. Finally, ultrasound guided biopsy of the liver proved stage II sarcoidosis. Steroid therapy was initiated and the splenic and hepatic lesions seen with ultrasound and CT scan disappeared. CONCLUSION - Sarcoidosis is usually suspected following chest X-ray or during chest CT examination. Nevertheless, our case demonstrates that multiple lesions in the spleen or liver may indicate sarcoidosis even in the absence of thoracic lesions. Biopsy taken from the lesions can lead to adequate diagnosis.]

Lege Artis Medicinae

DECEMBER 20, 2003

[CEREBRAL AMYLOID ANGIOPATHY - A FATAL CASE OF RECURRENT MULTIFOCAL CEREBRAL HEMORRHAGE]

POGÁNY Péter, HERMANN Zsuzsa

[Atherosclerosis and hypertension are the leading etiological factors in the pathogenesis of cerebral hemorrhage. With old age though, several other factors may appear of which cerebral amyloid angiopathy (CAA) is of major importance. This condition is characterized by the deposition of β-amyloid in the leptomeningeal vessels as well as in the small and medium sized arteries of the cerebral cortex and it is not associated with systemic amyloidosis. This pathological protein is also seen in the brains of otherwise healthy older individuals and may also appear in other diseases such as Alzheimer disease, Down-syndrome, vascular malformations, spongiform encephalopathy and dementia pugilistica. The condition may be asymptomatic but it may also cause cerebral hemorrhage, dementia or various transient neurological symptoms. Most cases are sporadic, but familial subtypes have also been described.]

Lege Artis Medicinae

DECEMBER 20, 2005

[LINKAGE OF POSTPRANDIAL LIPAEMIA AND GENES MUTATIONS IN FAMILIAL DYSLIPIDEMIA]

REIBER István

[The familial combined hyperlipidemia (FCH) is the most common form of heritable lipid disorder. The prevalence of FCH is 0.5 to 2.0% in the general population, and 15 to 20% in the survivors of myocardial infarction before the age of 60 years. Healthy people spend most part of their life in postprandial state, which is the sum of the 6-8 hours after each main meal spanning over 20 or 24 hour per day. After the ingestion of the fat rich meal the intestinal chylomicrons disturbs the balance of lipid metabolism. The disorder of the lipid transport does not always manifest itself in the fasting state when the lipid transport system is yet at poise. So, the measuring of fasting triglyceride does not reflect exactly the metabolic capacity and the true atherogen risk of the subject. The healthy FCH family members may have got abnormal higher and extended postprandial lipemia contrast of the normal fasting triglyceride levels. The distributions of PvuII and HindIII polymorphisms in FCH are different from normolipidemic controls. At the same time, there is significantly higher incidence of the apo e4 allele. The apo E4/3 genotypes have got higher and extended postprandial lipemia in FCH subjects. In the investigated international and Hungarian FCH groups have got the minor allele of apolipoprotein AV T/C polymorphism more frequently. The carrying status of the minor allele is accompanied with higher fasting lipid levels and associated with higher and extended postprandial lipemia. The Hungarian results suggest a decreased and extended catabolism of the remnants in FCH caused by apoAV T/C promoter variation that seems to have a more direct effect on the postprandial status than that of apoE 3/3-4/3 polymorphism. The knowledge of characteristics of postprandial lipemia influenced by the mutations of genes described by us are more useful as only the fasting triglyceride level and it is as effective as LDL- or HDL-cholesterol value in the measuring of prognosis of development of vascular disease with athero-thrombotic origin.]

Lege Artis Medicinae

MAY 26, 2008

[THE REAL FACE OF JUVENILE POLYPOSIS SYNDROME - MALIGNANCY IN A DISEASE PREVIOUSLY THOUGHT TO BE BENIGN]

TAM Beatrix, SALAMON Ágnes, BAJTAI Attila, NÉMETH Annamária, KISS János, SIMON László

[INTRODUCTION - The majority of colorectal cancer cases is sporadic, but familial and autosomal dominant forms should also be considered. Juvenile polyposis syndrome is an autosomal dominant condition caused by mutations in the SMAD4 or the BMPR1A gene. Typically, numerous hamartomatous polyps develop in the upper gastrointestinal and the colorectal area. In contrast to earlier opinions, some of these polyps may transform malignantly, like in the case presented here, at the age of 34-35 years on average. CASE REPORT - During the eighteen-year continuous care of the young man treated for juvenile polyposis, more than a hundred polyps were resected from the gastrointestinal tract. After an eigth-year intermission of surveillance because of insufficient compliance, the patient presented in a severe clinical condition caused by metastatic colorectal cancer. He died after a short palliative therapy at the age of 31. Based on the family tree, all of his living adult first-degree relatives were subsequently examined and juvenile polyposis syndrome was also diagnosed in his older brother. Genetic testing revealed a mutation in the BMPR1A gene in the clinically affected brother, one of his daughters, and also in the deceased proband's child. CONCLUSION - Genetic testing made it possible to relieve the mutation-free relatives of the anxiety and particularly of a number of unnecessary, mainly invasive examinations, while mutation carriers can be given the best possible clinical surveillance.]

Lege Artis Medicinae

MARCH 21, 2009

[THE REAL FACE OF JUVENILE POLYPOSIS SYNDROME - MALIGNANCY IN A DISEASE PREVIOUSLY THOUGHT TO BE BENIGN]

TAM Beatrix, SALAMON Ágnes, BAJTAI Attila, NÉMETH Annamária, KISS János, SIMON László

[INTRODUCTION - The majority of colorectal cancer cases is sporadic, but familial and autosomal dominant forms should also be considered. Juvenile polyposis syndrome is an autosomal dominant condition caused by mutations in the SMAD4 or the BMPR1A gene. Typically, numerous hamartomatous polyps develop in the upper gastrointestinal and the colorectal area. In contrast to earlier opinions, some of these polyps may transform malignantly, like in the case presented here, at the age of 34-35 years on average. CASE REPORT - During the eighteen-year continuous care of the young man treated for juvenile polyposis, more than a hundred polyps were resected from the gastrointestinal tract. After an eigth-year intermission of surveillance because of insufficient compliance, the patient presented in a severe clinical condition caused by metastatic colorectal cancer. He died after a short palliative therapy at the age of 31. Based on the family tree, all of his living adult first-degree relatives were subsequently examined and juvenile polyposis syndrome was also diagnosed in his older brother. Genetic testing revealed a mutation in the BMPR1A gene in the clinically affected brother, one of his daughters, and also in the deceased probands child. CONCLUSION - Genetic testing made it possible to relieve the mutation-free relatives of the anxiety and particularly of a number of unnecessary, mainly invasive examinations, while mutation carriers can be given the best possible clinical surveillance.]