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Clinical Neuroscience

SEPTEMBER 30, 2020

[Prognostic significance of invasion in glioblastoma]


[Glioblastoma is the most common malignant CNS tumor, its surgical removal is hindered by the tumors invasive nature, while current anti-tumor therapies show limited effectiveness – mean overall survival is 16-24 months. Some patients show minimal response towards standard oncotherapy, however there are no routinely available prognostic and predictive markers in clinical practice to identify the background of mentioned differences in prognosis. This research aims to identify the prognostic significance of invasion-related extracellular (ECM) components. Patient groups with different prognoses were created (OS: group A <16 months, group B > 16 months), and internationally recognized prognostic markers (IDH1 mutation and MGMT promoter hyper-methylation) were tested in the flash-frozen tumor samples. Furthermore, the mRNA levels of 46 invasion-related ECM molecules were measured. Clinical data of the patients who have been operated on at the University of Debrecen Clinical Center Department of Neurosurgery and treated at the Department of Clinical Oncology showed no significant differences except for survival data (OS and PFS), and reoperation rate. All samples were IDH wild type. MGMT promoter hypermethylation rate showed significant differences (28.6% vs 68.8%). The expressional pattern of the invasion-related ECM molecules, i.e. the invasion spectrum also showed major differences, integrin β2, cadherin-12, FLT4/VEGFR-3 and versican molecules having signficantly different mRNA levels. The accuracy of the inivasion spectrum was tested by statistical classifier, 83.3% of the samples was sorted correctly, PPV was 0.93. The difference found in the reoperation rate when comparing different prognostic groups aligns with literature data. MGMG promoter region methylation data in Hungarian samples has not been published yet, and further confirming current knowledge urges the implementation of MGMT promoter analysis in clinical practice. Studying the invasion spectrum provides extra information on tumors, as a prognostic marker it helps recognizing more aggressive tumors, and calls attention to the necessity of using anti-invasive agents in GBM therapies in the future.]

Clinical Neuroscience

SEPTEMBER 30, 2020

Late simultaneous carcinomatous meningitis, temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting with mono-symptomatic vertigo – a clinico-pathological case reporT

JARABIN András János, KLIVÉNYI Péter, TISZLAVICZ László, MOLNÁR Anna Fiona, GION Katalin, FÖLDESI Imre, KISS Geza Jozsef, ROVÓ László, BELLA Zsolt

Although vertigo is one of the most common complaints, intracranial malignant tumors rarely cause sudden asymmetry between the tone of the vestibular peripheries masquerading as a peripheral-like disorder. Here we report a case of simultaneous temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting as acute unilateral vestibular syndrome, due to the reawakening of a primary gastric signet ring cell carcinoma. Purpose – Our objective was to identify those pathophysiological steps that may explain the complex process of tumor reawakening, dissemination. The possible causes of vestibular asymmetry were also traced. A 56-year-old male patient’s interdisciplinary medical data had been retrospectively analyzed. Original clinical and pathological results have been collected and thoroughly reevaluated, then new histological staining and immunohistochemistry methods have been added to the diagnostic pool. During the autopsy the cerebrum and cerebellum was edematous. The apex of the left petrous bone was infiltrated and destructed by a tumor mass of 2x2 cm in size. Histological reexamination of the original gastric resection specimen slides revealed focal submucosal tumorous infiltration with a vascular invasion. By immunohistochemistry mainly single infiltrating tumor cells were observed with Cytokeratin 7 and Vimentin positivity and partial loss of E-cadherin staining. The subsequent histological examination of necropsy tissue specimens confirmed the disseminated, multi-organ microscopic tumorous invasion. Discussion – It has been recently reported that the expression of Vimentin and the loss of E-cadherin is significantly associated with advanced stage, lymph node metastasis, vascular and neural invasion and undifferentiated type with p<0.05 significance. As our patient was middle aged and had no immune-deficiency, the promoting factor of the reawakening of the primary GC malignant disease after a 9-year-long period of dormancy remained undiscovered. The organ-specific tropism explained by the “seed and soil” theory was unexpected, due to rare occurrence of gastric cancer to metastasize in the meninges given that only a minority of these cells would be capable of crossing the blood brain barrier. Patients with past malignancies and new onset of neurological symptoms should alert the physician to central nervous system involvement, and the appropriate, targeted diagnostic and therapeutic work-up should be established immediately. Targeted staining with specific antibodies is recommended. Recent studies on cell lines indicate that metformin strongly inhibits epithelial-mesenchymal transition of gastric cancer cells. Therefore, further studies need to be performed on cases positive for epithelial-mesenchymal transition.

Clinical Neuroscience

MARCH 30, 2020

CANOMAD syndrome with respiratory failure

SALAMON András, DÉZSI Lívia, RADICS Bence, VARGA Tímea Edina, HORTOBÁGYI Tibor, TÖMÖSVÁRI Adrienn, VÉCSEI László, KLIVÉNYI Péter, RAJDA Cecília

CANOMAD (chronic ataxic neuropathy, ophthalmoplegia, M-protein agglutination, disialosyl antibodies) syndrome is a rare polyneuropathy. IgM paraproteins react with ganglioside-containing disialylated epitopes resulting in dorsal root ganglionopathy and B-lymphocyte infiltration of cranial and peripheral nerves. Clinical features include ataxia, slight muscle weakness, areflexia, sensory- and cranial nerve symptoms. Case studies have reported the efficacy of rituximab and intravenous immunoglobulin (IVIg) treatments. We present the case of a 57-year-old man, who had difficulty walking, with numbness and clumsiness in all limbs. He had areflexia, vibratory sensation loss and ataxia. Laboratory tests showed IgM monoclonal components and disialosyl antibodies in the serum. Nerve conduction studies indicated severe sensorimotor demyelinating polyneuroradiculopathy. Despite IVIg and rituximab treatments, the patient’s disease course gradually worsened and he died of respiratory failure. Neuropathological examination revealed dorsal column- and dorsal root atrophy with mixed mononuclear cell infiltration. This article aims to draw attention to this syndrome, and the use of early potent immunosuppressive treatment to improve patients’ quality of life.

Clinical Neuroscience

MARCH 30, 2019

Secretory meningioma with bone infiltration and orbital spreading

KÁLOVITS Ferenc, TAKÁTS Lajos, SOMOGYI Katalin, GARZULY Ferenc, TOMPA Márton, KÁLMÁN Bernadette

Secretory meningioma is a rare form of meningiomas which differentiates from the meningothelial subtype. It is characterized by significant peritumor edema and distinct immunohistochemical and molecular genetic profiles. We present a middle aged female patient with secretory meningioma infiltrating the orbital bone from the primary cranial base location and causing exophthalmos, features rarely described with this tumor. Surgical resection was challenging because of the associated brain swelling and rich vascularization of the tumor. Imaging and immunohistochemical studies revealed characteristic hallmarks of secretory meningioma. While histologically it was a benign tumor, due to the orbital bone and soft tissue infiltration, postoperative management of neurological sequelae was challenging. This case highlights distinctive clinical, imaging and histological features along with individual characteristics of a rare form of meningiomas.

Clinical Neuroscience

SEPTEMBER 30, 2018

Acute motor and sensory axonal neuropathy associated with Sjögren’s syndrome


Sjögren’s syndrome (SS) is an autoimmune disease with mononuclear cell infiltration and destruction of the lacrimal gland and salivary glands, which cause dryness of the eyes and mouth. The most common neurological condition seen in SS is peripheral neuropathy. Initial manifestation of SS as an acute fulminant peripheral neuropathy is extremely rare. We report a 42-year-old patient presenting with acute motor sensory-axonal neuropathy in the presence of SS. She showed partial response to intravenous immunoglobulin but favourable clinical improvement was seen after initiation of corticosteroid treatment.

Lege Artis Medicinae

JUNE 20, 2016

[Neurological symptoms in a patient with treated multiple myeloma]


[INTRODUCTION - Meningeal infiltration by multiple myeloma is rare. Its incidence among cases of multiple myeloma is 1%. CASE REPORT - Multiple myeloma was diagnosed in a 53-year-old woman in December 2014. After chemotherapy, the disease was treated with autologous bone marrow transplantation in June 2015. Remission was observed through two months, but in August the patient was hospitalized due to severe headache with neck stiffness. Meningitis or viral encephalitis were suspected following her investigation. She was taken to the Intensive Care Unit because of a progression to status epilepticus. The EEG-examination revealed generalized slow wave activity and a right temporal epileptiform focus manifesting rarely. Clinical brain death developed on the 17th day in hospital. DISCUSSION - Although meningeal infiltration is infrequent in multiple myeloma, the present case report draws attention to this possibility. ]

Clinical Neuroscience

OCTOBER 05, 2013

[Characterization of CD4+ and CD8+ Tregs in a Hodgkin’s lymphoma patient presenting with myasthenia-like symptoms]

KRAUSZ Ludovic Tibor, MAJOR Zoltán Zsigmond, MURESANU Dafin Fior, CHELARU Eugen, NOCENTINI Giuseppe, RICCARDI Carlo

[The co-occurrence of Hodgkin’s lymphoma (HL) and myasthenia gravis (MG) is a rare phenomenon that is sometimes considered a paraneoplastic manifestation. There are a few documented cases in which myasthenia symptoms manifested only after the surgical removal of the tumor. However, the biological basis of this association is unknown. One hypothesis is that it derives from the infiltration of the residual thymic tissue by the developing tumor. In our case, the myasthenic symptoms led to the HL diagnosis. Our objective was to investigate the T cell phenotype in a HL patient presenting myasthenia-like symptoms. In patients with autoimmune disease, Tregs are usually decreased, but in some diseases, they appear to be increased. It has been speculated that this phenomenon may occur due to a homeostatic attempt by the immune system to control the expansion of auto-reactive effector cells. In the described patient the proportion of lymphoma infiltrating Tregs was high (more than 10% of CD4+ and 1.34% of CD8+ cells), suggesting that Tregs are increased in patients suffering from HL and eventually of myasthenia gravis. Treg involvement in HL is controversial and is currently under investigation. In this context, our data may contribute to a better understanding of the underlying mechanism of the link between HL and autoimmune phenomena.]

Clinical Neuroscience

SEPTEMBER 30, 2012

[Administration of preemptive analgesia by diclofenac to prevent acute postcraniotomy headache]

SIMON Éva, BÁNK Judit, GÁL Judit, SIRÓ Péter, NOVÁK László, FÜLESDI Béla, MOLNÁR Csilla

[Purpose - Postcraniotomy headache (PCH) is a frequent perioperative complication in neuroanesthesia. The aim of the present work was to assess the incidence of PCH and to test the efficacy and safety of preoperatively administered diclofenac. Methods - Patients undergoing craniotomies for intracranial tumor resections were enrolled. In the case group 100 mg diclofenac p.o. one hour prior to surgery was used as a preemptive analgesic along with infiltration of the surgical site with a combination of lidocaine and epinephrine. In controls only surgical site infiltration was used. VAS scores were assessed preoperatively, on the day of surgery (DoS), on the 1st and 5th postoperative days. Results - We have found that PCH of any severity is between 50-90% during the first five days after surgery. The number of cases characterized as “no pain” significantly decreased in the early postoperative period, but remained in both groups still higher on the 5th postoperative day than observed preoperatively. In both groups, the number of headaches characterized as mild pain remained relatively stable and substantial increases in case numbers were observed in moderate and severe headaches, showing a declining tendency over time in the postoperative period. A significant effect of diclofenac pretreatment was observed compared to controls on DoS (χ2: 10.429, p<0.015), on the 1st (χ2: 8.75, p<0.032) and 5th postoperative days (χ2: 14.3, p<0.002). Conclusions - The relatively low incidence of severe PCH on day five in the diclofenac group may indicate that preoperatively administered diclofenac effectively reduces postcraniotomy headache. A randomized study is encouraged to test this hypothesis.]

Hypertension and nephrology

MAY 20, 2012

[Sándor Gerő, the researcher clinician (1904-1992)]

GÁCS János

[Sándor Gerő presents two theories concerning the origin of atherosclerosis. The first one is called “primary lipid infiltration concept” which means the penetration of high concentration plasma lipids into the arterial wall without its damage. The other theory for the origin of atherosclerosis is primary damage of the vascular wall (namely of fibers, mucopolysaccharid etc.) which is followed by lipid infiltration. In the literature it is named “primary vascular concept” of atherosclerosis. The author investigates the two possibilities with experimental and clinical methods and concludes that primary vascular damage is more probable to be the origin of atherosclerosis.]

Clinical Neuroscience

JULY 30, 2012

[Selective ultrastructural vulnerability in the cuprizone-induced experimental demyelination]

ÁCS Péter, KOMOLY Sámuel

[Background and purpose - It has been reported that multiple sclerosis has four different neuropathological subtypes, and two of them (type III and IV) are characterized by primary oligodendrocyte loss. However, the exact pathomechanism that lead to oligodendrocyte apoptosis in human demyelinating diseases is still elusive. The copper chelator cuprizone induces primary oligodendrocyte apoptosis and consequent demyelination in well defined areas of the mouse brain. Nevertheless, the precise subcellular events that result in oligodendrocyte cell death in the cuprizone model are still unknown. We aimed to study the ultrastructural alterations that might induce oligodendrocyte apoptosis in the cuprizone experimental demyelination model. Methods - C57BL/6 mice were given cuprizone for two, 21 and 35 days to induce demyelination to investigate early pathological events, and different stages of demyelination. In addition, mice were given cuprizone for 35 days and were allowed to recover for two or 14 days to study early and late remyelination. After the cuprizone treatment, mice were sacrificed and the corpus callosum, the superior cerebellar peduncle, the optic nerve and the sciatic nerve were studied by electron microscopy. Results - The ultrastructural analysis revealed that cuprizone induced oligodendrocyte apoptosis is accompanied by the formation of giant mitochondria in the affected cells in the corpus callosum and in the superior cerebellar peduncle. Apoptosis of the myelin producing cells was present through the whole cuprizone challenge. Severe demyelination occurred after three weeks of cuprizone administration associated with massive macrophage infiltration and astrocytosis of the demyelinated areas. Axons and neurons remained unaffected. Conclusion - The formation of giant mitochondria in myelin producing oligodendrocytes is the first pathological sign in the cuprizone experimental demyelination. Mitochondrium pathology in the cuprizone challenge might serve as a useful model to study the pathomechanism of multiple sclerosis subtypes (III and IV) characterized by primary oligodendrocyte degeneration.]