Clinical Neuroscience

[European treatment recommendation of neuromyelitis optica spectrum disorders: critical remarks and case discussion]


MAY 30, 2012

Clinical Neuroscience - 2012;65(05-06)

[Neuromyelitis optica is a demyelinating disease of the central nervous system mediated by antibodies against the waterchannel aquaporin4 (AQP4). In a number of cases the clinical manifestation is spatially limited. Such events of separate longitudinally extensive transverse myelitis (LETM) or relapsing/bilateral optic neuritis (RION/BON) are defined as NMO spectrum diseases. The diagnosis is further challenged by anti-AQP4 seronegative cases. While chronic immunosuppressive therapy should be introduced in definitive NMO, treatment strategy of the NMO spectrum is less defined. Recent EFNS guidelines recommend chronic immunosuppressive treatment of NMO spectrum diseases depending on the clinical course even in AQP4-seropositive cases. Presenting a case with relapsing optic neuritis, here we emphasize the importance of early immunosuppressive therapy in all seropositive NMO spectrum diseases regardless of relapse severity, in order to prevent an upcoming devastating relapse, i.e. NMO conversion.]



Further articles in this publication

Clinical Neuroscience

[Effect of two month positive airway pressure therapy on the structure of sleep, cognitive function and anxiety]


[Obstructive sleep apnea is a common disorder, characterized by repeated episodes of upper airway obstruction during sleep, resulting intermittent hypoxia and disruption of the normal sleep pattern, which caused cognitive dysfunction in these patients. Nasal continuous positive airway pressure is the treatment of choice for this disorder. The aim of the study is to evaluate the effect of short-term positive airway pressure on sleep pattern (polisomnographic measures), cognitive function and anxiety. Twenty four newly diagnosed and previously untreated patients with obstructive sleep apnea were evaluated a battery of neuropsychological tests before and after 2 and a half months of the treatment. We focused on working memory, short and long-term episodic memory, executive functions, anxiety and subjective sleepiness. Our results showed that the two and half month of treatment improved the respiration during sleep, sleep pattern and the subjective sleepiness. We found improvement in short- and long-term verbal memory, and complex working memory. Despite of treatment we did not find improvement in visuospatial learning. These results reveal that 2 and a half months of positive airway pressure treatment restored not only the normal respiration during sleep and normal sleep pattern, but also the cognitive functions. Our study suggests that cognitive dysfunction is at least partial reversible in obstructive sleep apnea patients after positive airway pressure treatment.]

Clinical Neuroscience

[Non-invasive brain stimulation for relieving acute and chronic pain]


[Controlling pain has always been one of the biggest challenges of medical science. Despite pharmacological developments, still many patients suffer from long-lasting pain. During the last 40 years several surgical interventions have been used to modulate the activity of the central nervous system in order to control chronic, pharmacoresistant pain. Because such interventions may involve very serious adverse events, safer and at least equally efficient methods are still required. In the 90’s new techniques of non-invasive brain stimulation have been introduced that enable the facilitation or inhibition of distinct cortical areas. These methods are based on the electrical stimulation of brain structures and to date they have been successfully used to modulate perceptual, cognitive and motor functions in healthy subjects and various diseases as well. In this review we describe such techniques of non-invasive brain stimulation, namely repeated transcranial magnetic stimulation and transcranial direct current stimulation and review the current literature about their efficacy in controlling acute and chronic pain.]

Clinical Neuroscience

[Prognostic factors of primary spinal tumors]

LAZÁRY Áron, BORS István Béla, SZÖVÉRFI Zsolt, RÓNAI Márton, VARGA Péter Pál

[Aims - Primary spinal tumors are rare diseases and there are less objective data in the international literature. We analyzed the epidemiology and clinical consequences of primary spinal tumors based on the clinical experience of the National Center for Spinal Disorders. Methods - Demographic and clinical data of 300 patients treated in our institute between 1995 and 2007 was collected retrospectively and analysed. Results - Beyond the relatively more frequent pathologies (chordoma, myeloma multiplex) we treated in our hospital some of the very rare types of tumors (spinal leiomyosarcoma, synovial sarcoma). Primary spinal tumors are most often located in the lumbosacral region causing most frequently (73%) local or radiating pain. Modern therapy of these patologies is based on the surgical intervention. Mean operation time was 130 minutes, mean blood loss was 650 ml in our pratice during these often technically challenging surgeries. We found a significant association among the operation time, the blood loss and the extension of the tumor (p<0.01). Histology (p<0.0001), severity of symptomes (p<0.05) and blood loss (p<0.05) were significantly related to mortality. Local recurrence was more than 5-fold in case of patients previously operated in another institute (p<0.0001). Conclusions - We successfully determined some significant prognostic factor on clinical behavior of primary spinal tumors performing a large scale retrospective study. Long time follow up of the patients and completion of our database with prospective data are planned for the future.]

Clinical Neuroscience

[New minimal invasive surgical techniques in spine surgery]


[The last decade has brought significant development in spine surgery. As in all field of surgery, introduction of the minimal invasive, atraumatic procedures characterized our activities. The number of short and long-time complications were significantly reduced and the effectiveness of operations were markedly improved by the new technical conditions, for example by the use of neuronavigation, surgical microscope, intraoperative fluoroscopy, high speed drill and the widespread of keyhole concept. The applied multislice CT imaging and the high resolution MRI enabled to improve the accuracy of the planned surgical procedures and to reduce the mortality and morbidity of operations. In our studies technical methods were investigated and new developments were established in the field of minimal invasive spine surgery. The National Institute of Neurosurgery's spinal surgical team pioneers further development and application of novel minimal invasive procedures. Applied methods of vanguard surgical procedures include split laminotomy, the “archbone” technique, the “over the top” decompression, the multilevel hemi-semi laminectomy, the supraforaminal “burr hole”, the facet joint sparing “open tunnel” techniques or parasplit minimal invasive approaches. The new innovative surgical techniques are applied in our daily routine and meet international trends by utilizing benefits of minimal invasive spinal surgery. Using our newly developed innovative techniques allow to decompress neural elements in case of spinal canal stenosis and to remove the intramedullary and extramedullary space-occupying lesions located in the spinal canal and spreading extraspinally through the neuroforamen. These techniques are specially tailored to preserve structural integrity and stability of the spinal column, and allow at the same time to minimize resection of and injury to tissues not directly involved in the pathologic processes. In our studies a classification system of spatial localization of pathological lesions and processes in spinal canal was developed by us. Using this classification system enables the surgeon to select and apply the appropriate minimal invasive technique from dorsal direction and to remove the space-occupying lesions located in the spinal canal. The minimal invasive techniques were characterized and summarized. This overview of the minimal invasive techniques can be applied and recommended in the daily routine of spine surgery. We proudly employ novel surgical techniques having been developed in our institution. These techniques are internationally recognized and applied in our practice on daily basis as well.]

Clinical Neuroscience

[Acute and chronic stress induced changes in gene transcriptions related to Alzheimer’s disease]

SÁNTHA Petra, PÁKÁSKI Magdolna, FAZEKAS Örsike, SZŰCS Szabina, FODOR Eszter Klára, KÁLMÁN János ifj., KÁLMÁN Sára, SZABÓ Gyula, JANKA Zoltán, KÁLMÁN János

[Preclinical and clinical studies demonstrate that stress may be implicated in the risk of neurodegenerative diseases such as Alzheimer’s disease (AD). Our study aimed to investigate the effects of acute and chronic immobilization stress (IS) on the gene transcriptions of β-actin, amyloid precursor protein (APP) and mitogen activated protein kinase-1 (MAPK-1), proteins related to synaptic plasticity and neuronal degeneration. Male Wistar rats were exposed to IS for five hours daily for 3 days (acute stress) or through 7-14-21 days (chronic stress). At the end of exposure periods, total RNA was purified from the cortex and hippocampus. The amounts of β-actin, APP and MAPK-1 mRNA were determined with real time PCR method. Our results indicate that the mRNA expression of β-actin and APP followed a U-shaped time-response curve. Both acute and chronic IS caused a significant increase in β-actin and MAPK-1 mRNA expression. Significant APP mRNA elevation was observed only by the 3rd week after RS. Our findings demonstrate that both acute and chronic IS lead to gene transcriptional changes of β-actin, APP and MAPK-1. These proteins maintain the normal function of the cytoskeleton and the synaptic plasticity. The above changes may lead to cognitive deterioration, and the development of AD.]

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Clinical Neuroscience

Life threatening rare lymphomas presenting as longitudinally extensive transverse myelitis: a diagnostic challenge

TOLVAJ Balázs, HAHN Katalin, NAGY Zsuzsanna, VADVÁRI Árpád, CSOMOR Judit, GELPI Ellen, ILLÉS Zsolt, GARZULY Ferenc

Background and aims – Description of two cases of rare intravascular large B-cell lymphoma and secondary T-cell lymphoma diagnosed postmortem, that manifested clinically as longitudinally extensive transverse myelitis (LETM). We discuss causes of diagnostic difficulties, deceptive radiological and histological investigations, and outline diagnostic procedures based on our and previously reported cases. Case reports – Our first case, a 48-year-old female was admitted to the neurological department due to paraparesis. MRI suggested LETM, but the treatments were ineffective. She died after four weeks because of pneumonia and untreatable polyserositis. Pathological examination revealed intravascular large B-cell lymphoma (IVL). Our second case, a 61-year-old man presented with headache and paraparesis. MRI showed small bitemporal lesions and lesions suggesting LETM. Diagnostic investigations were unsuccessful, including tests for possible lymphoma (CSF flow cytometry and muscle biopsy for suspected IVL). Chest CT showed focal inflammation in a small area of the lung, and adrenal adenoma. Brain biopsy sample from the affected temporal area suggested T-cell mediated lymphocytic (paraneoplastic or viral) meningoencephalitis and excluded diffuse large B-cell lymphoma. The symptoms worsened, and the patient died in the sixth week of disease. The pathological examination of the presumed adenoma in the adrenal gland, the pancreatic tail and the lung lesions revealed peripheral T-cell lymphoma, as did the brain and spinal cord lesions. Even at histological examination, the T-cell lymphoma had the misleading appearance of inflammatory condition as did the MRI. Conclusion – Lymphoma can manifest as LETM. In cases of etiologically unclear atypical LETM in patients older than 40 years, a random skin biopsy (with subcutaneous adipose tissue) from the thigh and from the abdomen is strongly recommended as soon as possible. This may detect IVL and provide the possibility of prompt chemotherapy. In case of suspicion of lymphoma, parallel examination of the CSF by flow cytometry is also recommended. If skin biopsy is negative but lymphoma suspicion remains high, biopsy from other sites (bone marrow, lymph nodes or adrenal gland lesion) or from a simultaneously existing cerebral lesion is suggested, to exclude or prove diffuse large B-cell lymphoma, IVL, or a rare T-cell lymphoma.

Clinical Neuroscience

Cases of inborn errors of metabolism diagnosed in children with autism

CAKAR Emel Nafiye, YILMAZBAS Pınar

Autism spectrum disorder is a neurodevelopmental disorder with a heterogeneous presentation, the etiology of which is not clearly elucidated. In recent years, comorbidity has become more evident with the increase in the frequency of autism and diagnostic possibilities of inborn errors of metabolism. One hundred and seventy-nine patients with diagnosis of autism spectrum disorder who presented to the Pediatric Metabolism outpatient clinic between 01/September/2018-29/February/2020 constituted the study population. The personal information, routine and specific metabolic tests of the patients were analyzed retrospectively. Out of the 3261 patients who presented to our outpatient clinic, 179 (5.48%) were diagnosed with autism spectrum disorder and were included in the study. As a result of specific metabolic examinations performed, 6 (3.3%) patients were diagnosed with inborn errors of metabolism. Two of our patients were diagnosed with classical phenylketonuria, two with classical homocystinuria, one with mucopolysaccharidosis type 3D (Sanfilippo syndrome) and one with 3-methylchrotonyl Co-A carboxylase deficiency. Inborn errors of metabolism may rarely present with autism spectrum disorder symptoms. Careful evaluation of the history, physical examination and additional findings in patients diagnosed with autism spectrum disorder will guide the clinician in the decision-making process and chose the appropriate specific metabolic investigation. An underlying inborn errors of metabolism may be a treatable cause of autism.

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

Alexithymia is associated with cognitive impairment in patients with Parkinson’s disease

SENGUL Yildizhan, KOCAK Müge, CORAKCI Zeynep, SENGUL Serdar Hakan, USTUN Ismet

Cognitive dysfunction (CD) is a common non-motor symptom of Parkinson’s disease (PD). Alexithy­mia is a still poorly understood neuropsychiatric feature of PD. Cognitive impairment (especially visuospatial dysfunction and executive dysfunction) and alexithymia share com­mon pathology of neuroanatomical structures. We hypo­thesized that there must be a correlation between CD and alexithymia levels considering this relationship of neuroanatomy. Objective – The aim of this study was to evaluate the association between alexithymia and neurocognitive function in patients with PD. Thirty-five patients with PD were included in this study. The Toronto Alexithymia Scale–20 (TAS-20), Geriatric Depression Inventory (GDI) and a detailed neuropsychological evaluation were performed. Higher TAS-20 scores were negatively correlated with Wechsler Adult Intelligence Scale (WAIS) similarities test score (r =-0.71, p value 0.02), clock drawing test (CDT) scores (r=-0.72, p=0.02) and verbal fluency (VF) (r=-0.77, p<0.01). Difficulty identifying feelings subscale score was negatively correlated with CDT scores (r=-0.74, p=0.02), VF scores (r=-0.66, p=0.04), visual memory immediate recall (r=-0.74, p=0.01). VF scores were also correlated with difficulty describing feelings (DDF) scores (r=-0.66, p=0.04). There was a reverse relationship bet­ween WAIS similarities and DDF scores (r=-0.70, p=0.02), and externally oriented-thinking (r=-0.77,p<0.01). Executive function Z score was correlated with the mean TAS-20 score (r=-62, p=0.03) and DDF subscale score (r=-0.70, p=0.01) Alexithymia was found to be associated with poorer performance on visuospatial and executive function test results. We also found that alexithymia was significantly correlated with depressive symptoms. Presence of alexithymia should therefore warn the clinicians for co-existing CD.