Clinical Neuroscience

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

KALMÁR Tibor1, MARÓTI Zoltán1, VADVÁRI Árpád2, HALMOSI Ágnes3, KÁLOVITS Ferenc4,5, KÁLMÁN Bernadette5,6

JULY 30, 2019

Clinical Neuroscience - 2019;72(07-08)

DOI: https://doi.org/10.18071/isz.72.0273

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.

AFFILIATIONS

  1. University of Szeged, Institute of Pediatrics and Pediatric Health Center, Szeged Hungary
  2. Markusovszky University Teaching Hospital, Department of Radiology, Szombathely
  3. Markusovszky University Teaching Hospital, Department of Ophthalmology, Szombathely
  4. Markusovszky University Teaching Hospital, Department of Neurosurgery, Szombathely
  5. University of Pécs, School of Medicine, School of Graduate Studies, Pécs
  6. Department of Molecular Pathology of the Markusovszky University Teaching Hospital, Szombathely

COMMENTS

0 comments

Further articles in this publication

Clinical Neuroscience

[Sleep habits among preschool- and schoolchildren]

FUSZ Katalin, RITECZ Bernadett, BALOGH Brigitta, TAKÁCS Krisztina, SOMLAI Eszter, RAPOSA L. Bence, OLÁH András

[Objective - Our aim is to evaluate sleep habits, sleep quality and influencing factors among preschool- and schoolchildren. Method - Two questionnaires were recorded. Questionnaire 1 dealt with sleeping habits, breastfeeding and health behavior of preschool children and infant, and it contained the abbreviated version of the Children’s Sleep Habits Questionnaire. Questionnaire 2 dealt with health behavior and the application of sleep hygiene rules, as well as it contained the Athens Insomnia Scale. Subjects - We assessed a total of 1063 questionnaires: 516 kindergarten children participated in our online survey across the country; 547 primary and secondary school students participated in the 2nd questionnaire survey in Szolnok. Results - Parents’ observation shows that the average nighttime sleeping time of kindergarten children is 10 hours 20 minutes on weekdays and 10 hours 36 minutes on weekends. The most popular sleeping habits in kindergarten age: teal reading (65.1%) and co-sleeping (42.8%). Parents of infants used breastfeeding (50.4%) and rocking (43.2%) most frequently before sleep. Co-sleeping has a positive influence on the length of lactation. Among the preschool sleeping habits we have proved a number of positive effects of teal reading, while watching television have negative effects. The sleep quality of school-age children according to the Athens Insomnia Scale is 6.11 points (SD: 4.11), 19% of the children are insomniac. Their sleep time is 7 hours 31 minutes on weekdays and 9 hours 30 minutes on weekends. The usage of good health behavior and sleep hygiene rules positively influence sleep quality and sleep duration. Conclusions - With our results, we would like to draw the attention of children and parents to the importance of sleeping and using sleep hygiene rules.]

Clinical Neuroscience

[Treatment of complex regional pain syndrome with amitriptyline]

KOMOLY Sámuel

[Introduction - Complex regional pain syndrome is a di­stressing neuropathic pain condition without known etiology and evidence based treatment. Case presentation - Here a posttraumatic severe case of complex regional pain syndrome is presented, successfully treated by amitriptyline monotherapy. Amitriptyline is one of the most effective evidence based treatments of peri­pheral diabetic neuropathic pain and other neuropathic pain syndromes. Discussion - Amitriptyline seems to be effective to decrease pain, autonomic and motor symptoms in chronic regional pain syndrome. Conclusion - Controlled trials may be warranted to test the effectiveness of amitriptyline in complex regional pain syndrome.]

Clinical Neuroscience

A case report of Morvan syndrome

AYTAC Emrah, ACAR Türkan

Morvan syndrome is a rare disease characterized by peripheral nerve hyperexcitability, encephalopathy, dys­autonomia and significant insomnia. The patient, who was included in the present study, was followed-up at our clinics for confusion, myokymia, hyperhidrosis, epileptic seizures, tachycardia, agitation, hypokalemia, and hyponatremia. The cranial MRI of the patient demonstrated hyperintensities at the T2 and FLAIR sections of the medial temporal lobe and insular lobes. Electromyography and neurotransmission examination results were concordant with peripheral nerve hyperreactivity. Contactin-associated protein-like 2 antibodies and leucine-rich glioma inactivated protein 1 antibodies were detected as positive. The patient was diagnosed with Morvan syndrome; intravenous immunoglobulin and corticosteroid treatment was started. Almost full remission was achieved. This very rare syndrome implies challenges in diagnosis and treatment; however, remission can be achieved during the follow-up. In addition, caution is needed in the long-term follow-up of these patients regarding the development of malignancies.

Clinical Neuroscience

Investigation of risk factors, topographic location and stroke mechanisms of unilateral isolated and posterior cerebral ARTERY thalamic infarcts

GÖKCAL Elif, SENGUL Yildizhan, USLU Ilgen Ferda

Aim - In this study, we aimed to examine the risk factors, topographic features and stroke mechanisms of acute ischemic unilateral infarcts of thalamus. Methods - Patient with isolated thalamic infarct and those with posterior cerebral artery (PCA) infarction who were admitted to our hospital between January 2014 and January 2017 with acute unilateral thalamic infarction (TI) were included in this study (isolated thalamic infarction/ isolated TI; thalamic and posterior cerebral artery infarction/PCA+TI). Demographic characteristics and vascular risk factors of the patients were determined. Thalamic infarct areas were recorded topographically as anterior, posteromedial, ventrolateral, posterolateral, more than one area, and variant areas. Stroke mechanism was determined according to the criteria of „Trial of Org 10172 in Acute Stroke Treatment” (TOAST). Patients with isolated TI and PCA TI were compared according to risk factors, stroke mechanism and infarct topography. Results - Forty-three patients with a mean age of 63.3 ± 14.5 years were included in the study. Twenty-eight patients (60.1%) were found to have isolated TI and the remaining 15 patients (34.9%) had PCA+TI. 32.1% of patients with isolated TI had sensory symptoms on presentation, and 60% of patients with PCA-TI had sensorimotor symptoms. The mean age, the mean score on National Institutes of Health Stroke Scale (NIHSS) and the mean frequency of atrial fibrillation were higher in PCA+TI patients than in isolated-TI patients (p: 0.04, p: 0.004, p: 0.02 respectively). 32.6% of the patients had ventrolateral, 30.2% had posteromedial involvement. Ventrolateral topography was seen in 46.7% of the PCA+TI patients, while posteromedial topography was seen in 39.3% of the isolated-TI patients. 53.6% of the isolated-TI had small vessel disease etiology, while 40% of the PCA+TI had cardioembolic etiology, and the other 40% had large artery atherosclerosis. Conclusion - Our study showed that the most ommon stroke mechanism in patients with thalamic infarction is the small vessel disease. Isolated TI and PCA+TI patients differ in terms of etiologic mechanism and infarct topography. Variant territorial involvement and multiple area involvements can be quite common in thalamic infarcts.

Clinical Neuroscience

Attitude of spine surgeons towards the application of 3D technologies - a survey of AOSpine members

ÉLTES Endre Péter, KISS László, BARTOS Márton, EÖSZE Zsolt, SZÖVÉRFI Zsolt, VARGA Pál Péter, LAZÁRI Áron

Background - 3D technologies (3D virtual and physical model, 3D printing, computer aided engineering, finite element analysis based simulations) play an important role in personalized spine surgery. Objective - In collaboration with AOSpine a global, online survey-based study was performed in order to determine the acceptance rate and the factors which stand against the wider spread of 3D technologies. Methods - A survey containing 21 questions was developed and divided into five pages, every page corresponding to one chapter. Our analysis is based on the responses of 282 spine surgeons from 57 countries. To interpret our results in a global context, we used the Human Development Index of the respondent's countries in comparisons. Results - Significant difference between the AOSpine regions (p ≤ 0.05) was found, with the highest acceptance in Asia-Pacific region. There was no significant difference in acceptance score according to the field of spine surgery, or the surgical experience in years (p=0.77, and p=0.19). In the case of public practice, we found significantly higher acceptance compared to private and mixed (public and private) surgical practice (p ≤ 0.05). The acceptance of the technology varied based on the respondent’s resident country’s Human Development Index and was significantly different between „Medium” vs “Very high” (p = 0.0005) and „High” vs „Very high” (p=0.019) category. Significant positive correlation was found between the acceptance score and the HDI score (Spearman test, ρ = 0.37, p = 0.007). The main limitation factor was identified as the lack of information. Conclusion - There is high interest among spine surgeons towards the incorporation of 3D technologies into the clinical practice. Education, the healthcare system, and the economic environment plays a major role in acceptance. Our results provide the basis of a strategy to promote the application of 3D technologies.

All articles in the issue

Related contents

Clinical Neuroscience

[The role of MRI in measuring the effectivity of disease modifying treatments II]

KINCSES Zsigmond Tamás, TÓTH Eszter, FRICSKA-NAGY Zsanett, FÜVESI Judit, RAJDA Cecília, BENCSIK Krisztina, VÖRÖS Erika, CSOMOR Angéla, PALKÓ András, VÉCSEI László

[The paraclinical examinations, principally the MRI have an increasing significance in the diagnosis of multiple sclerosis. However, MRI markers also have a prominent role in monitoring of the disease-course and activity, and also in the planning of possible therapeutic changes. In accordance with previously published international guidelines, in this article we propose a protocol for the monitoring the treatment efficacy in multiple sclerosis. This could be the basis of a consensus based guideline to be implemented in Hungary.]

Clinical Neuroscience

Long-term follow-up results of concomitant chemoradiotherapy followed by adjuvant temozolomide therapy for glioblastoma multiforme patients. The importance of MRI information in survival: Single-center experience

LUKÁCS Gábor, TÓTH Zoltán, SIPOS Dávid, CSIMA Melinda, HADJIEV Janaki, BAJZIK Gábor, CSELIK Zsolt, SEMJÉN Dávid, REPA Imre, KOVÁCS Árpád

Introduction - Glioblastoma multiforme (GBM) is the most common malignant primary anomaly of central nervous system. The GBM infiltrates the nearly sturctures from the initial tumor and its metastatic attribution is well known. The aim of our single-centered retrospective study was to introduce the importance of postoperative medical imaging confirmation of total tumor resection for patient with GBM combined concomitant and adjuvant chemoradiotherapy on a 10 year long patient follow up. Methods - From January 2006 to April 2015 we registered 59 patients with newly diagnosed GBM at the University of Kaposvár Health Center Institute of Diagnostic Imaging and Radiation Oncology. The histological diagnosis was confirmed by a proficient neuropathologist (World Health Organisation WHO; grade IV astrocytoma). According to histological status if the ECOG performance status of patients allowed it the mutidisciplinary oncoteam recommended adjuvant chemoradiotherapy all features strictly by Stupp protocol. (60 Gy dose on the gross tumor volume and 2-3 cm margin for the clinical target volume with parallel 75 mg/m2 TMZ. Four weeks after monotherapial phase patients had to recieve 6 cycles of TMZ first cycle with 150 mg/m2 up to 200 mg/m2). The irradiation was carried out by a conformal three dimensional planning system. Results - 59 patients with the median age of 63 (range 17-84) year. Our sample counted 34 male patients and 25 woman patients. 14 patients underwent gross total tumor resection while, 39 patients underwent partial resection and the rest from our sample 6 patients passed through biopsy. Statistical analysis showed a lengthier survival among males than females, with a median survival of 13 months for males and females, the OS of 26.209 for males, meanwhile 15.625 for females. However, the difference is not considerable (log-rank p=0.203). Our study found that the estimated survival of patients at least 50 years old is significantly shorter at a median survival of 12 months (log rank p=0.027) than that of patients below 50 years of age at a median survival of 23 months. The longest estimated median survival was calculated with patients of ECOG '0' condition (16 months). However, no significant difference was found in the estimated survival of patients of different ECOG conditions (log-rank p=0.146). Based on the extent of surgery, complete resection resulted in the longest average survival of 36.4 months, followed by 21.5 months among patients with biopsy, and 15.8 months among patients with partial resection. Different surgical procedures, however, did not result in significant differences in survival (log-rank p=0.059). The overal survival of patients who had complete resection confirmed by MRI compared with the overal survival of patients with residual tumor confirmed by MRI as well we can estimate that there is significant difference between these two groups (p=0,004). Conclusion - Despite complex and intense treatment, recurrence is inevitable and causes relatively rapid death. In our analysis complete resection, as defined from the neurosurgeon’s report and postoperative MRI, resulted in an independently significant improvement in OS. Our results are the evidences that the treatment of patients with glioblastoma multiforme in Hungary is at least on the same level as any other developed European countries.

Clinical Neuroscience

[The role of MRI in measuring the effectivity of disease modifying treatments I]

TÓTH Eszter, BENCSIK Krisztina, VÖRÖS Erika, FRICSKA-NAGY Zsanett, FÜVESI Judit, RAJDA Cecília, CSOMOR Angéla, PALKÓ András, VÉCSEI László, KINCSES Zsigmond Tamás

[MRI has a significant role in the diagnosis of multiple sclerosis. The newer and newer treatment options of the disease make it necessary to monitor the effectiveness of the therapy. Besides the clinical signs (clinical relapses and progression), the different MRI parameters can also reflect the disease activity. In our current article we summarize those MRI markers, which best predict the long-term disability, based on the international standards.]

Clinical Neuroscience

[Childhood sporadic type of hemiplegic migraine with arteria cerebri media hypoperfusion]

NAGY Csaba, BAJZIK Gábor, SKOBRÁK Andrea, CSORBA Eszter, LAJTAI Anikó, BALOGH Gábor, NAGY Ferenc, VAJDA Zsolt

[Hemiplegic migraine is a rare subtype of migraine that is associated with reversible motor weakness in the aura phase. This is an uncommon form of migraine usually starting in childhood. The purpose of this case report is to highlight the differential diagnostic difficulty of the first attack. We describe a case, where the fluctuating unilateral motor weakness and aphasia suggested that the patient had ischaemic stroke. Nevertheless the brain MRI and MR angiography, the measured 5-hydroxyindole acetic acid (5-HIAA) concentration changes and the spontaneously improving clinical status proved the diagnosis of hemiplegic migraine. The MRI and MR angiography was very beneficial in establishing the correct diagnosis in this case. To distinguish between the familiar and sporadic type of hemiplegic migraine further genetic tests can be carried out.]

Clinical Neuroscience

[Magnetic resonance imaging in the course of alemtuzumab and teriflunomide therapy]

MIKE Andrea, KINCSES Zsigmond Tamás, VÉCSEI László

[Our work aimed to review the published results of magnetic resonance imaging (MRI) obtained in the course of alemtuzumab and teriflunomide therapy in multiplex sclerosis. In multiplex sclerosis MRI sensitively detects subclinical pathological processes, which do not manifest clinically in the early course of the disease, however have substantial significance from the viewpoint of the long-term disease prognosis. MRI has an increasingly important role in the early monitoring of the therapeutic efficacy. In the last 15 years several clinical trials have been conducted with alemtuzumab and teriflunomide in multiple sclerosis providing evidence about the favourable clinical effect of these drugs. MRI images were acquired in these trials as well, and the results published recently in the scientific literature. These MRI results denote the suppression of the disease activity and the neurodegenerative processes, which may imply a favourable effect on the long-term prognosis of the disease. ]