Clinical Neuroscience

Case report of a woman with anti amphiphysin positive stiff person syndrome

MANHALTER Nóra, GYÖRFI Orsolya, BOROS Erzsébet, BOKOR Magdolna, FAZEKAS Ferenc, DÉNES Zoltán, FABÓ Dániel, KAMONDI Anita, ERÕSS Loránd

MAY 30, 2017

Clinical Neuroscience - 2017;70(05-06)


Stiff person syndrome is a rare neuroimmunological disease, characterized by severe, involuntary stiffness with superimposed painful muscle spasms, which are worsened by external stimuli. The classical form is associated with high levels of antibodies against glutamic acid decarboxylase. One of the variant forms is associated with antibodies against amphiphysin. This entity is a paraneoplastic syndrome, caused primarily by breast cancer, secondarily by lung cancer. Symptomatic therapy of anti amphiphysin positive stiff person syndrome includes treatment with benzodiazepines and baclofen (including intrathecal baclofen therapy). The effect of immunological therapies is controversial. Treatment of the underlying cancer may be very effective. In this report, we describe a 68 year old female presenting with an unusally rapidly developing anti amphiphysin positive stiff person syndrome, which was associated with breast cancer. Her painful spasms abolished after intrathecal baclofen treatment was initiated. Her condition improved spontaneously and significantly after cancer treatment, which enabled to start her complex rehabilitation and the simultaneous dose reduction of the intrathecal baclofen. The bedridden patient improved to using a rollator walker and the baclofen pump could be removed 18 monthes after breast surgery. This highlights the importance of cancer screening and treatment in anti amphiphysin positive stiff person syndrome cases.



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Clinical Neuroscience

[EEG-based cerebral networks in 14 neurological disorders]

DÖMÖTÖR Johanna, CLEMENS Béla, CSÉPÁNY Tünde, EMRI Miklós, FOGARASI András, HOLLÓDY Katalin, PUSKÁS Szilvia, FEKETE Klára, KOVÁCS Attila, FEKETE István

[Background - Brain networks have not been systematically investigated yet in most neurological disorders. Purpose - To investigate EEG functional connectivity (EEGfC) networks in 14 neurological disorders. Patients - Potentially eligible patients were collected from clinical and EEG databases. All the available clinical data and EEG records were critically revised. All the patients who suffered of a single neurological disorder (out of the 14) and had a good quality EEG recording entered the study. Confoundig factors as comorbidity and CNS-active drug effects were eliminated as far as possible. EEG analysis - Three minutes of resting-state, waking EEG activity were selected for analysis. Current source density (CSD) values were computed for 2394 cortical voxels by Low Resolution Electromagnetic Tomography (LORETA). Thereafter, Pearson correlation coefficients were computed between all pairs of 23 cortical regions of interest (ROI) in each hemisphere (LORETA Source Correlation, LSC software). Computation was carried out for conventional EEG broad bands and very narrow bands (1 Hz bandwidth) between 1 and 25 Hz as well. Correlation coefficients of each group were statistically compared to our normative EEG (LSC) database by two-talied t-tests. Bonferroni-corrected p<0.05 values were accepted as statistically significant, and were graphically displayed as topographical networks. Results and conclusion - Group-specific networks were demonstrated. However, non-specific networks, charasteristic for most groups, were detected as well. Common finding were: decreased connectivity in the alpha band and increased connectivity in the delta, theta bands and upper-beta band. Decreased alpha-band connectivity presumably reflected primary lesional effects and on the other hand, non-specific vulnerability of “rich club connections”. Increased connectivity in the slow bands presumably indicated adaptive-compensatory activity of brain homeostasis. ]

Clinical Neuroscience

[Experience with natalizumab-treatment at Semmelweis University]

GOMBOS Barbara, ILJICSOV Anna, BARSI Péter, HEGEDÛS Katalin, SIMÓ Magdolna

[Multiple sclerosis is an autoimmune demyelinating disorder of the central nervous system. During the last two decades, numerous disease modifying drugs have been introduced for the treatment of the relapsing-remitting form of the disease. Since 2010, natalizumab (NTZ) treatment has been used as a second-line therapy for patients with breakthrough disease. In comparison to conventional immunomodulant drugs, NTZ has a more specific effect in that it prevents the entry of immune cells into the central nervous system without interfering with systemic immune response. The efficacy and the safety of NTZ have been confirmed by several studies. The most severe side-effect of NTZ is progressive multifocal leukoencephalopathy, which has been associated with an increased incidence in patients with anti-JCV antibody positivity, and in those who have been undergoing NTZ treatment for over two years and who have received prior immunosuppressive therapy. In the present study, our experience with natalizumab treatment of 37 patients at the Department of Neurology of Semmelweis University during the last 6 years is presented. We have observed a significant decrease of disease activity in our patients; in many cases the disease has become inactive both clinically (36/37) and radiologically (34/37). The patients’ quality of life has improved significantly during the treatment. In accordance with the literature, we confirm that NTZ is a highly effective treatment in a carefully selected patient group, and can be administered without significant inconvenience to the patient. ]

Clinical Neuroscience

The role of the insula in the parieto-frontomedial epileptic network. Clues from successful surgical treatment

BALOGH Attila, AIMEN Anwar, KELEMEN Anna, ERÕSS Loránd, FABÓ Dániel

We present a case of MRI negative SMA seizure with the seizure onset zone in the secondary leg area on the superior bank of the Sylvian fissure, localized with multiscale electro-clinical and neuroradiological examinations. The 34-year-old female patient’s intractable epilepsy started at age 14. She had diffuse pain aura in her left leg followed by tonic posturing with fully preserved consciousness suggesting parieto-fronto-medial seizure propagation. Her daily nocturnal SMA seizures became drug-resistant. Multiple 3T MRI images and neuropsychological evaluations were normal. Interictal PET detected a right parietal and insular FDG hypometabolism. The seizure onset zone and the symptomatogenic zone were localized by invasive electrophysiology. The insular deep electrode showed the propagation of ictal activity with an onset in the secondary sensory leg area through the insula to the fronto-medial surface. Eighteen spontaneous seizures, electrical cortical stimulation and cortical mapping confirmed the designated area of the resection, which was later proved macroscopically abnormal during surgery. The histological and immunohistological workup confirmed focal cortical dysplasia (IIb type). Postoperative postprocessing morphometry of the preoperative MRI study confirmed the lesion in the right inferior parietal lobe. The patient remained seizure free after surgery for more than 4 years, and medication free for the last two years. Our results concluded that the insula has a „relay” or „node” function in the parieto-opercular-fronto-medial epileptic network. The insular functional connectivity predisposed frontal propagation of the epileptic activity in the connectome of her epilepsy. The three-way insular structural connectivity has determining function on the seizure propagation.

Clinical Neuroscience

[Prevention of invasive meningococcal infection, recognition and first treatment of the disease in primary care]


[Neisseria meningitidis, the meningococcus, is a Gram-negative diplococcal bacterium that is only found naturally in humans. The meningococcus is part of the normal microbiota of the human nasopharynx and is commonly carried in healthy individuals. In some cases systemic invasion occurs, which can lead to meningitis and/or septicemia. Invasive disease caused by Neisseria meningitidis is potentially devastating, with a high case fatality rate and high rates of significant sequelae among survivors after septicaemia or meningitis. Between 2006-2015 every year between 34 and 70 were the numbers of the registered invasive disease because of Neisseria meningitis, the morbidity rate was 0.2-0.7⁰⁄₀₀₀₀. Half of the diseases (50.7%) were caused by B serotype N. meningitidis, 23.2% were C serotype. In this article the authors summarise what you must do and must not do as primary care physician when suddenly meeting a young patients suspected of having meningococcus infection. ]

Clinical Neuroscience

[Relationship between the number of hours of sunshine and the number of (violent) suicides in Hungary]

BOZSONYI Károly, ZONDA Tamás, FÜLÖP Andrea, BÁLINT Lajos

[Aim - Studying the impact of the sunshine on the numbers of suicides. The number of suicides is highest in the late spring and early summer months, while it is lowest in the cold, gloomy winter. Although the exact causes are still un-known, there are some theories about this phenomenon. A number of studies conducted in recent years have conclud-ed that the rise in suicide rate during the warm months might be due to an increased exposure to sunlight, especially in the cases of the violent method. We studied the validity of this hypothesis on a large Hungarian database. Methods and subjects - We analyzed the number of monthly hours of sunshine and the number of suicides by sex and by violent vs. non-violent method over a 360-month period. Our sample consisted of 127 877 committed suicides between 1971 and 2000. The parabolic trend of seasonality had to be removed from the suicide time series, then regression analysis was conducted on the seasonally adjusted data. Results - Our analysis revealed that in Hungary there was no statistically significant direct relationship between the number of hours of sunshine and the number of suicides. Moreover, there was no correlation between the hours of sunshine and the number of violent suicides either. Conclusion - If the above claim were confirmed in subsequent research, it would mean that our current therapeutic regime should be reconsidered during the spring-summer seasons.]

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Clinical Neuroscience

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

[What happens to vertiginous population after emission from the Emergency Department?]

MAIHOUB Stefani, MOLNÁR András, CSIKÓS András, KANIZSAI Péter, TAMÁS László, SZIRMAI Ágnes

[Background – Dizziness is one of the most frequent complaints when a patient is searching for medical care and resolution. This can be a problematic presentation in the emergency department, both from a diagnostic and a management standpoint. Purpose – The aim of our study is to clarify what happens to patients after leaving the emergency department. Methods – 879 patients were examined at the Semmel­weis University Emergency Department with vertigo and dizziness. We sent a questionnaire to these patients and we had 308 completed papers back (110 male, 198 female patients, mean age 61.8 ± 12.31 SD), which we further analyzed. Results – Based on the emergency department diagnosis we had the following results: central vestibular lesion (n = 71), dizziness or giddiness (n = 64) and BPPV (n = 51) were among the most frequent diagnosis. Clarification of the final post-examination diagnosis took several days (28.8%), and weeks (24.2%). It was also noticed that 24.02% of this population never received a proper diagnosis. Among the population only 80 patients (25.8%) got proper diagnosis of their complaints, which was supported by qualitative statistical analysis (Cohen Kappa test) result (κ = 0.560). Discussion – The correlation between our emergency department diagnosis and final diagnosis given to patients is low, a phenomenon that is also observable in other countries. Therefore, patient follow-up is an important issue, including the importance of neurotology and possibly neurological examination. Conclusion – Emergency diagnosis of vertigo is a great challenge, but despite of difficulties the targeted and quick case history and exact examination can evaluate the central or peripheral cause of the balance disorder. Therefore, to prevent declination of the quality of life the importance of further investigation is high.]

Clinical Neuroscience

Neuroscience highlights: Main cell types underlying memory and spatial navigation

KRABOTH Zoltán, KÁLMÁN Bernadette

Interest in the hippocampal formation and its role in navigation and memory arose in the second part of the 20th century, at least in part due to the curious case of Henry G. Molaison, who underwent brain surgery for intractable epilepsy. The temporal association observed between the removal of his entorhinal cortex along with a significant part of hippocampus and the developing severe memory deficit inspired scientists to focus on these regions. The subsequent discovery of the so-called place cells in the hippocampus launched the description of many other functional cell types and neuronal networks throughout the Papez-circuit that has a key role in memory processes and spatial information coding (speed, head direction, border, grid, object-vector etc). Each of these cell types has its own unique characteristics, and together they form the so-called “Brain GPS”. The aim of this short survey is to highlight for practicing neurologists the types of cells and neuronal networks that represent the anatomical substrates and physiological correlates of pathological entities affecting the limbic system, especially in the temporal lobe. For that purpose, we survey early discoveries along with the most relevant neuroscience observations from the recent literature. By this brief survey, we highlight main cell types in the hippocampal formation, and describe their roles in spatial navigation and memory processes. In recent decades, an array of new and functionally unique neuron types has been recognized in the hippocampal formation, but likely more remain to be discovered. For a better understanding of the heterogeneous presentations of neurological disorders affecting this anatomical region, insights into the constantly evolving neuroscience behind may be helpful. The public health consequences of diseases that affect memory and spatial navigation are high, and grow as the population ages, prompting scientist to focus on further exploring this brain region.

Clinical Neuroscience

The etiology and age-related properties of patients with delirium in coronary intensive care unit and its effects on inhospital and follow up prognosis

ALTAY Servet, GÜRDOGAN Muhammet, KAYA Caglar, KARDAS Fatih, ZEYBEY Utku, CAKIR Burcu, EBIK Mustafa, DEMIR Melik

Delirium is a syndrome frequently encountered in intensive care and associated with a poor prognosis. Intensive care delirium is mostly based on general and palliative intensive care data in the literature. In this study, we aimed to investigate the incidence of delirium in coronary intensive care unit (CICU), related factors, its relationship with inhospital and follow up prognosis, incidence of age-related delirium and its effect on outcomes. This study was conducted with patients hospitalized in CICU of a tertiary university hospital between 01 August 2017 and 01 August 2018. Files of all patients were examined in details, and demographic, clinic and laboratory parameters were recorded. Patients confirmed with psychiatry consultation were included in the groups of patients who developed delirium. Patients were divided into groups with and without delirium developed, and baseline features, inhospital and follow up prognoses were investigated. In addition, patients were divided into four groups as <65 years old, 65-75 yo, 75-84 yo and> 85 yo, and the incidence of delirium, related factors and prognoses were compared among these groups. A total of 1108 patients (mean age: 64.4 ± 13.9 years; 66% men) who were followed in the intensive care unit with variable indications were included in the study. Of all patients 11.1% developed delirium in the CICU. Patients who developed delirium were older, comorbidities were more frequent, and these patients showed increased inflammation findings, and significant increase in inhospital mortality compared to those who did not develop delirium (p<0.05). At median 9-month follow up period, rehospitalization, reinfarction, cognitive dysfunction, initiation of psychiatric therapy and mortality were significantly higher in the delirium group (p<0.05). When patients who developed delirium were divided into four groups by age and analyzed, incidence of delirium and mortality rate in delirium group were significantly increased by age (p<0.05). Development of delirium in coronary intensive care unit is associated with increased inhospital and follow up morbidity and mortality. Delirium is more commonly seen in geriatric patients and those with comorbidity, and is associated with a poorer prognosis. High-risk patients should be more carefully monitored for the risk of delirium.

Clinical Neuroscience

Autonomic nervous system may be affected after carpal tunnel syndrome surgery: A possible mechanism for persistence of symptoms after surgery

ONDER Burcu, KELES Yavuz Betul

After carpal tunnel surgery, some patients report complaints such as edema, pain, and numbness. Purpose – The aim of this study was to evaluate autonomic nervous system function in patients with a history of carpal tunnel surgery using sympathetic skin response (SSR). Thirty three patients (55 ±10 years old) with a history of unilateral operation for carpal tunnel syndrome were included in the study. The SSR test was performed for both hands. Both upper extremities median and ulnar nerve conduction results were recorded. A reduced amplitude (p=0.006) and delayed latency (p<0.0001) were detected in the SSR test on the operated side compared to contralateral side. There was no correlation between SSR and carpal tunnel syndrome severity. Although complex regional pain syndrome does not develop in patients after carpal tunnel surgery, some of the complaints may be caused by effects on the autonomic nervous system.