Ferenc Kövér

Morphometric changes of gray matter in Parkinson's disease with depression: a voxel-based morphometry study.

The origin of the high rate of depression in idiopathic Parkinsons disease (PD) is unknown. We applied voxel‐based morphometry (VBM), as a sensitive tool in detection of gray matter MR density alterations, to find differences in depressed and nondepressed PD patients. Patients with idiopathic PD were classified into depressed (DPD) and nondepressed (NDPD) groups based on the Montgomery‐Åsberg Depression Rating Scale (MADRS). Subsequently, a group comparisons were performed between depressed PD (n = 23), nondepressed PD (n = 27) and normal healthy controls (NC, n = 16). There was no difference in gray matter density comparing healthy controls to any PD groups. However, when NDPD and DPD cohorts were compared, density alteration of the bilateral orbitofrontal, bilateral rectal gyrus, and also the right superior temporal pole was detected in the depressed subgroup. Exploratory analyses revealed an inverse correlation of MADRS scores and severity of VBM alteration in these regions beside the right medial temporal gyrus, anterior and medial cingular gyrus, and parahippocampal gyrus. These results suggest that depression in PD is related to gray matter decrease in the bilateral orbitofrontal and right temporal regions as well as the limbic system.

MRI-assessed volume of left and right hippocampi in females correlates with the relative length of the second and fourth fingers (the 2D: 4D ratio)

Atrophy of the left or right side of the hippocampus has been related to cognitive deficits and psychiatric disease. In this study, we examined the correlation between the hippocampal volume laterality index and the relative lengths of the second (index finger) and fourth (ring finger) digits (2D:4D) in healthy female subjects. The 2D:4D ratio is fixed in utero, and the ratio is higher in women than in men. There is evidence that this ratio is an indicator of the intrauterine concentration of testosterone, which influences the development of different regions of the brain. Assessing the volume of different parts of the brain of 40 healthy adult female students by magnetic resonance imaging (MRI), we found that the 2D:4D ratio was associated with an asymmetry in the hippocampal sub-regions. Smaller volume on the left side was found in the posterior part of the hippocampus in females with a low (masculine type) 2D:4D ratio. On the other hand, smaller volume on the left side was found in the middle part of the hippocampus in females with a high (female type) 2D:4D ratio. Thus, the development of the middle and posterior regions of the hippocampal formation may respond in opposite ways to prenatal levels of testosterone. Other brain regions such as the amygdala, the cerebral cortex, the total volume hippocampus, and the head of the hippocampus did not show such a difference.

Natural course of LGI1 encephalitis: 3-5 years of follow-up without immunotherapy

Antibodies against LGI1 (leucin-rich glioma-inactivated 1 protein) are associated with limbic encephalitis (LE), which is characterized by a favorable outcome following immunotherapy. Here, we present two cases, where antibodies against LGI1 were detected in the sera 36 and 53 months after acute LE, respectively, and none of the patients received immunotherapy. LE showed characteristics of LGI1 encephalitis in both cases, including low sodium content in the sera; disorientation, hallucination, short-term memory loss; and epileptic seizures. One patient had faciobrachial tonic seizures. MRI indicated bilateral inflammation of the hippocampus in one case. We reviewed longitudinal clinical and MRI data covering 53 and 36 months after LE without immunotherapy, respectively. Both patients became seizure-free and spontaneously recovered with mild/moderate cognitive impairment. No relapses have been observed. Follow-up brain MRI indicated early hippocampal sclerosis and global brain atrophy in one case characterized by more pronounced cognitive deficit. Memory and verbal fluency were affected most during the natural course of LGI1 encephalitis. LGI1 encephalitis had a monophasic course and spontaneously improved, suggesting that a relatively benign natural course may contribute to the favorable outcome observed after immunotherapy. Our data also indicate that LGI1 antibodies can be present in the sera without clinical disease activity.

IMPLANTED DEEP BRAIN STIMULATOR AND 1.0 TESLA MAGNETIC RESONANCE IMAGING

There is a great need for MRI examinations of patients who have previously undergone deep brain stimulator (DBS) implantation. The current guidelines pertain only to a 1.5‐Tesla horizontal‐bore scanner complying with strict safety regulations. Moreover, almost all published in vitro and in vivo studies concerning patient safety are carried out on 1.5 Tesla MR scanners. The aim of our work is to share our clinical experience of 1.0‐Tesla brain MR imaging. During the past four years, 34 patients with different types of implanted DBS systems underwent 1.0‐Tesla MR examinations to answer diagnostic or clinical questions. Apart from the scanner type applied, all other safety instructions were strictly followed. The MRI itself made no significant difference to the measured impedances or the stimulation parameters required to achieve the optimal therapeutic results. From theoretical considerations, it may be assumed that 1.0‐Tesla MRI can be performed safely on DBS‐implanted patients, provided that all other recommendations are adhered to. J. Magn. Reson. Imaging 2006.

Intravascular lymphomatosis of the nervous system

Sirs: Intravascular lymphoma (IVL) is a rare and aggressive variant of diffuse large cell lymphoma [1–3]. Its rarity (one person per million), multiplicity of presentations, and absence of lymphoma cells in the reticuloendothelial system complicate early diagnosis [2– 5]. Most of IVL belong to systemic diffuse large B cell lymphomas (DLBCL), but aberrant expression of integrins prohibits extravasal migration [6]. Multifocal cortical and subcortical T2 hyperintense lesions were observed on the MRI of the brain (Fig. 1 A and Table 1). CSF showed albumino-cytological dissociation. Stereotactic brain biopsy revealed IVL. Cells displayed an activated B cell phenotype profile on immuno-staining (CD20+, MUM1+, Bcl-6+ and CD10–) (Fig. 1 B). In situ hybridiza-

Intravascular lymphoma presenting with neurological signs but diagnosed by prostate biopsy: suspicion as a key to early diagnosis

Dear Sir, Intravascular lymphoma (IVL) is a rare subtype of diffuse large B-cell lymphoma (DLBCL) characterized by neoplastic cells within the blood vessel lumina and occlusion of small vessels in different tissues [1,2]. The majority of the patients are presented with prominent or exclusive neurological symptoms [2–5]. Given its rarity (incidence: 1/1 million), the variety of clinical presentations and the absence of lymphoma cells in the rethiculo-endothelial system, early diagnosis is difficult, but critical for survival [2–7]. As diagnosis is provided by pathological examination of the affected tissues, particularly brain, a high index of suspicion is required. A 64-year-old man was admitted with a week history of subfebrility, dizziness and progressive confusional state. On physical examination, lymph nodes, liver and spleen were not palpated. There were no skin lesions. Body temperature was 37.8 C, blood pressure was 130/80 mmHg and pulse was 82/min with sinus rythm. Neurological examinations revealed acute confusional state, delirium with acustic and visual hallucinations and repeated, transient left-sided hemiparesis. Serum LDH (1393 U/l) and high-sensitive Creactive protein levels were elevated (hsCRP, 16.3 mg/l). Thrombocytopenia was found (82.7 · 10 platelets/l) but hemoglobin concentration was normal (135 g/l). Other blood sample tests were unremarkable including tumor, markers (PSA: 2.2 lg/l, CEA: 1.1 ng/ml; AFP: 1.1 lg/l; CA-125: 9 U/ml; CA-15-3: 15 U/ ml; CA-19-9: 3.8 U/ml) and systemic antibodies (ANA screen: 2.4 IU/ml; antidsDNA: 5.2 IU/ml; ANCA MPO3, PR3 IgG screen negative; anti-cardiolipin IgM, IgG screen negative; anti-B2-glycoprotein IgM, IgG screen negative; anti-phosphatidyl serine IgG: 4.0 U/ml, IgM: 0.7 U/ ml). Neuroimaging was performed twice. Following a negative cranial CT examination (slide thickness 4,5 mm, axial slice by slice mode with a Somatom Sensation 16 machine, Siemens, Germany), magnetic resonance imaging (MRI) of the brain did not indicate either signal alteration or enhancement (axial T2 turbo spin echo, TR: 6000 ms, TE: 93 ms, echo train: 18; coronal FLAIR, TR: 9000 ms, TE: 93 ms, echo train: 16; sagittal T1 gradient echo, TR: 440 ms, TE: 2.5 ms and diffusion-weighted ADC sequences, b = 0, b = 500, b = 1000 with 4 mm slide thickness performed by Siemens Trio Tim 3.0 T MRI machine, Erlangen, Germany) (Fig. 1a). Protein content of the cerebrospinal fluid was increased (1.2 g/l) but pathological cells and oligoclonal bands examined by isoelectric focusing were not found. Based on the clinical picture and laboratory abnormalities, IVL was suspected. As MRI was negative, abdominal and pelvic CT were performed to search for extracerebral manifestations. Enlarged adrenal glands and inhomogenously enhancing enlarged prostate gland suggested malignancy (Fig. 1b and c). Transrectal ultrasound guided prostate needle biopsy revealed large atypical lymphoid cells in the small venules and capillaries. After endogenous peroxidase blocking, slides were incubated with antibodies against CD3 (Dako, pre-diluted; Glostrup, Denmark), CD10 (Novocastra, 1:75; Newcastle, UK), CD20 (Novocastra, 1:400), Bcl-6 (Dako, 1:10), MUM1 (Dako, 1:30), GFAP (Bio-Genex, 1:750; San Ramon, CA, USA). The antibodies were visualized in an automated immunostainer (Ventana Medical System, Tucson, AZ, USA). Lymphoma cells were positive for CD20, MUM1, MIB-1 indicating an activated B-cell-like (ABC) phenotype (Fig. 1d). The first cycle of rituximabCHOP treatment (R-CHOP) resulted in resolution of neurological signs and normalization of laboratory parameters (LDH, CRP, platelet count). The patient has been in clinical remission for 5 months. The fever, mental state and transient neurological signs together with elevated LDH, hsCRP and thrombocytopenia were highly suggestive of IVL [2,4,6,7]. Increased protein in the CSF was also characteristic [4,6,7]. In the present case, MRI was negative despite of the clinical symptoms and signs. Brain MRI most often discloses signal alterations suggestive of small vessel ischemia or demyelination providing a site for stereotactic biopsy in IVL patients with neurological signs [6–8]. Cranial MRI may disclose non-specific hyperintense white matter lesions but are rarely normal in IVL [9–11]. Our recent case series indicated heterogeneous neuroimaging results in IVL, which may complicate diagnosis [7]. The negative MRI findings may be explained by incomplete and transitory obliteration of the small vessels. In the present case, the absence of signal alterations on MRI hindered brain biopsy. Therefore, search for extracerebral manifestations as potential biopsy sites was crucial to establish diagnosis. Abdominal CT was performed, which disclosed enlarged adrenal glands, a possible manifestation of IVL [7,8]. In addition, enhancement in the prostate, whilst PSA was normal, also suggested IVL rather than cancer, and provided a convenient site for biopsy. Rare case reports of IVL and large series of malignant lymphoma cases involving the prostate gland suggest that the diagnosis of solitary lymphoma or infiltration by a systemic lymphoma has to be taken into account if the PSA value is in the normal range [12– 17]. Prostate involvement has previously been described only in a few cases of intravascular B-cell lymphoma. In contrast to our case, the patients were referred to urology department due to lower urinary tract obstruction in those cases. Only a single patient presented neurological signs as well indicating lesions in the spinal cord [15–17]. In a review of 81 cases, prostate gland was not amongst diagnostic sites for in vivo diagnosis, indicating the rarity of prostate involvement [18]. In a recent review of eight neurological cases, no involvement of the prostate gland has been described [4]. In our recent case series, prostate gland was not affected [7]. Diffuse, CD20+ large B-cell lymphomas are known to be morphologically and immuno-phenotypically heterogeneous and can be divided into subtypes based on the expression of the late stage of B-cell

The effect of carotid stenting on rheological parameters, free radical production and platelet aggregation

INTRODUCTION Carotid artery stenting has become a possible treatment of significant carotid stenosis. The risk of stent occlusion and restenosis might be increased by abnormal rheological conditions amplified platelet aggregation and free radical production during the operation. AIMS The aim of our study was to assess the changes in hemorheological parameters, platelet aggregation, and catalase activity after endovascular treatment of carotid stenosis. METHODS 18 patients (11 men, ages 68 +/- 9 years and 7 women, ages 62 +/- 8 years) suffering from significant carotid stenosis and treated with carotid endovascular intervention were examined. Alteration in hemorheological parameters as well as epinephrine-, ADP-, and collagen-induced platelet aggregation were evaluated. Antioxidant reserve was characterized by the determination of catalase activity. The measurements were carried out directly before and after the procedure and 1, 2, 5 days and 1 month following the intervention. Preceding the operation the patients were administered a maximum dose (300 mg) of clopidogrel. RESULTS Hematocrit, plasma fibrinogen concentration (PFC) and whole blood-, and plasma viscosity values (WBV and PV) significantly decreased immediately after stenting (p<0.001). By the fifth day following the intervention the PFC, WBV, PV, red blood cell (RBC) aggregation and ADP-induced platelet aggregation significantly increased (p<0.0001) compared to values measured postprocedurally. At 1 month follow-up these parameters, except whole blood viscosity, decreased significantly compared to measurements made on the 5th day. On the other hand, catalase activity showed significant elevation by the end of the first month. CONCLUSION Hemorheological parameters and platelet aggregation showed specific changes following carotid stenting. Abnormal changes of the rheological conditions and increasing platelet activation are the most pronounced in the first week following stenting, which may lead to early stent occlusion. Oxidative stress production returned to baseline levels only by the end of the first month.

Susac’s syndrome: clinical characteristics of a Hungarian case

UNLABELLED Encephalopathy, recurrent occlusion of retinal arteries and hearing loss comprise the clinical picture of Susacs syndrome. The correct diagnosis is frequently missed because of incomplete clinical signs or negligence of previous symptoms. Early diagnosis and treatment can halt the progression and prevent permanent disability. METHODS Here, we describe a Hungarian case and review the clinical characteristics, diagnostic procedures and current concepts of therapy. RESULTS A 30-year-old female was admitted to our neurology department because of change in her personality, apathy, and difficulty in concentration. Brain MRI indicated multiple hyperintense T2-weighted lesions including cerebellum and corpus callosum. Protein content of the CSF was markedly elevated. The recurrent bilateral loss of vision and hearing along with migraine in her previous 2,5-year-long medical history suggested Susacs syndrome. Fundoscopy and fluorescein angiography indicated multiple occlusions of the retinal arteries, audiography revealed bilateral hearing loss. Systemic autoimmune and connective tissue diseases and thrombophilia were excluded. The markedly elevated protein in the cerebrospinal fluid supported Susacs syndrome. Chronic treatment with methylprednisolone resulted in remission of clinical signs. DISCUSSION Consideration of multiple clinical signs is an important key to the diagnosis of rare clinical entities like Susacs syndrome.A Susac-szindroma ritka, tobbszoros szervi erintettseggel jaro korkep, melyet encephalopathiabol, a retinat ellato arteria againak okkluziojabol es hallascsokkenesből allo triasz jellemez. Ritka előfordulasa, fluktualo lefolyasa es a hosszabb-rovidebb ideig inkomplett klinikai kep miatt sokszor nem ismerik fel, pedig az időben megkezdett kezeles a prognozist kedvezően befolyasolja. Modszer: Kozlemenyunkben egy beteg esetet ismertetjuk, es osszefoglaljuk a korkep legfontosabb ismerveit, diagnosztikai es terapias lehetősegeit. Eredmenyek: A 30 eves nőbeteg ismeretlen eredetű encephalopathia, napok alatt kialakulo szemelyisegvaltozas, meglassult gondolkodas, inditekhiany miatt kerult a pszichiatriai, majd a neurologiai klinikankra. A koponya MR-vizsgalata multiplex feherallomanyi laesiokat, liquorvizsgalata emelkedett osszfeherjet mutatott. Az anamnezisben szereplő ismetlődő ketoldali lataszavar, hallascsokkenes es migrenes fejfajas az encephalopathiaval egyutt a fiatal nőbeteg eseteben Susac-szindroma lehet...

Occlusive hydrocephalus complicating tuberous sclerosis: report of two cases.

Two patients—6 and 14 years old—with tuberous sclerosis are presented. Both developed a subependymal giant cell astrocytoma from nodules located near to the foramen of Monro. They caused obstruction of the cerebrospinal fluid pathways. Signs of raised intracranial pressure were detected in both patients, and one of them had also developed infantile spasm—Blitz‐Nick‐Salaam seizures. Cutaneous stigmata being characteristic for this entity were observed in both cases, but their mental development was unaffected. Diagnosis was based on computed tomography. Angiography did not reveal pathological vessels. The tumours were completely excised through transcallosal exposure in both cases. The patients have been symptom‐free during the follow‐up time of 1 and 2 years. Although the incidence of malignant transformation of tuberous sclerosis is less than 15% the disease generally has a poor prognosis which can be ascribed to sudden increase of intracranial pressure caused by obstruction of cerebrospinal fluid pathways by paraventricular tumours. However, regular follow‐up of paraventricular nodules and maintenance of patency of cerebrospinal fluid pathways by microsurgical methods in patients suffering from mild cerebral disorders offers a better chance of survival.

[The effect of carotid stenting on rheological parameters, free radical production and platelet aggregation].

INTRODUCTION Carotid artery stenting has become a possible treatment of significant carotid stenosis. The risk of stent occlusion and restenosis might be increased by abnormal rheological conditions amplified platelet aggregation and free radical production during the operation. AIMS The aim of this study was to assess the changes of the rheologic parameters, platelet aggregation, and oxidative stress after endovascular treatment of carotid stenosis. METHODS 18 patients (11 men, ages 68 +/- 9 years and 7 women, ages 62 +/- 8 years) suffering from significant carotid stenosis and treated with carotid endovascular intervention were examined. Alteration in hemorrheological parameters as well as epinephrine-, ADP-, and collagen-induced platelet aggregation were evaluated. Oxidative stress was characterized by the determination of catalase activity. The measurements were carried out directly before and after the procedure and 1, 2, 5 days and 1 month following the intervention. Preceding the operation the patients were administered a maximum dose (300 mg) of clopidogrel. RESULTS The hematocrit, the plasma fibrinogen concentration (Pfc) and whole blood-, and plasma viscosity (Wbv and Pv) decreased significantly immediately after stenting ( p < 0.001). By the fifth day following the intervention the Pfc, Wdv, Pv, red blood cell (Rbc) aggregation and ADP-induced platelet aggregation increased significantly ( p < 0.0001) compared to values measured after the procedure. At 1 month follow-up these parameters, excepting Wbv, decreased significantly compared to measurements made on the 5th day. On the other hand, catalase activity showed significant elevation by the end of the first month. CONCLUSION Hemorrheological parameters and platelet aggregation showed specific changes following carotid stenting. Abnormal changes of the rheological conditions and increasing platelet activation are the most pronounced in the first week following stenting, which may lead to the stents early occlusion. Oxidative stress production returned to baseline levels only by the end of the first month.