Clinical Neuroscience

[Clinicopathological variability in neurodegeneration with brain iron accumulation]

VINCZE András1,2, KAPÁS István3, MOLNÁR J. Mária4, KOVÁCS G. Gábor1

MARCH 24, 2010

Clinical Neuroscience - 2010;63(03-04)

[Neurodegeneration with brain iron accumulation (NBIA) is a rare, progressive neurodegenerative disorder with extrapyramidal and cognitive clinical symptoms characterized by iron accumulation predominantly in the globus pallidus, as well as extensive axonal spheroids in various regions of the brain. Recent studies indicate multiple genetic causes, however the illness can occur without obvious genetic background. The most frequent genetic form is the pantothene kinase associated neurodegeneration (PKAN) with mutation in the pantothenate kinase 2 (PANK2) gene. Further forms include phosphoslipase A2 (PLA2G6) gene mutation, neuroferritinopathy, and aceruloplasminaemia. To demonstrate the phenotypic variability associated with NBIA we present two patients. In the first patient iron deposition in the globus pallidus and axonal spheroids throughout the whole brain confirmed the neuropathological diagnosis of NBIA. Based on the long duration (27 years), the relatively late onset (at age of 13) of the disease, and the symmetrical hypointensity in the globus pallidus, without the eye-of-thetiger sign in cranial MRI, this case most likely represented an idiopathic form of NBIA but atypical PKAN may be also considered. In our second patient, who is still alive after duration of 9 years, MRI revealed the typical eye-of-the-tiger phenomenon that supported the clinical diagnosis of NBIA and was highly suggestive of PKAN. Since NBIA shows similarities with other neurodegenerative disorders, genetic examination may be essential in the diagnosis of this disease, however, cranial MRI together with the clinical picture may be highly indicative of NBIA.]


  1. Institute of Neurology, Medical University of Vienna, Vienna
  2. Department of Central Electron Microscope Laboratory, Medical University of Pécs, Pécs
  3. Department of Neurology, Jávorszky County Hospital, Vác
  4. Clinical and Research Centre for Molecular Neurology, Semmelweis University, Budapest



Further articles in this publication

Clinical Neuroscience

[Deep brain stimulation for treatment refractory obsessive-compulsive disorder - a case report]

CSIGÓ Katalin, DÖME László, HARSÁNYI András, DEMETER Gyula, RACSMÁNY Mihály

[In the last 30 years it has been a great development in the understanding and therapy of obsessive-compulsive disorder. Adequate pharmaco- and cognitive-behavior therapies reduce the symptoms in 40-60% of patients, so a remarkable portion of patients still remains refractory to conventional treatment. Neurosurgery - with it’s reversible and irreversible techniques - brought a breakthrough in the therapy of treatment refractory patients. In the present case, we represent a 3 months follow-up of an obsessive-compulsive patient treated by deep brain stimulation. In our case, the stimulation target was the anterior limb of internal capsule. The clinical symptoms were measured by Y-BOCS. In addition various neuropsychological tests were used to monitor patient’s executive functions before and 3 months after the deep brain stimulation. We found that obsessive-compulsive symptoms improved after three months of the stimulation. The neuropsychological tests showed improvement in some executive functions (e.g. fluency, set-shifting, decision making). On the other hand our results revealed severe neurocognitive - mainly attention skill - deficits in a treatment refractory obsessive-compulsive patient.]

Clinical Neuroscience

[Differential diagnosis of atypical Parkinsonian syndromes]


[Atypical Parkinson syndromes are distinguished from idiopathic Parkinson disease by insufficient or missing response to dopaminergic replacement therapy and therefore they have significantly unfavorable prognoses. Early differential diagnosis is very important for the patient. It enables the therapist to give suitable consults, to avoid unnecessary or inappropriate therapy, which are not free of medication side effects and furthermore facilitates the selection of adapted symptomatically medical and physical measures of treatment. In case of future development of neuroprotective or causally therapy strategies correct diagnosis will allow an early start of therapy. The differential diagnosis separation of the three clinical pictures from the idiopathic Parkinson disease with clinical criteria might be difficult in the early stage of disease. Additional neuroimaging and nuclear medical investigations may support the clinical probable diagnosis.]

Clinical Neuroscience

[Numbers, counting and calculating problems in view of cognitive neurology]


[The ability to count and calculate is a human-specific skill comprised of understanding numeric values and categories and performing numerical operations; it is an acoustic-verbal symbolic activity that may be expressed in writing and understood by reading. The neuronal bases and precursors of cognitive systems have been supplied to mankind by the process of evolution. Abilities to create symbols (speech, visual letter and number symbols) must have played a decisive role in the emergence of man from the world of primates. Although counting and calculating problems are classified into numerous types, two main forms of dyscalculia have practical importance: the acquired one (the loss of learned knowledge) and the developmental one (the disturbance of the acquisition of arythmetical knowledge).]

Clinical Neuroscience

[Neuron to glia - 15 years history of the cytoplasmic]

PAPP Mátyás

Clinical Neuroscience

[Movement analyzing devices for analyzing the actual state of patients with movement disorders]


[Movement analysis gives valuable information on the actual state of patients. Based on it, the early diagnosis and objective assessment of the progress of several diseases can be helped. Our research work has been focused on developing clinically applicable movement analyzing devices.]

All articles in the issue

Related contents

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

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

Simultaneous subdural, subarachnoideal and intracerebral haemorrhage after rupture of a peripheral middle cerebral artery aneurysm


The cause of intracerebral, subarachnoid and subdural haemorrhage is different, and the simultaneous appearance in the same case is extremely rare. We describe the case of a patient with a ruptured aneurysm on the distal segment of the middle cerebral artery, with a concomitant subdural and intracerebral haemorrhage, and a subsequent secondary brainstem (Duret) haemorrhage. The 59-year-old woman had hypertension and diabetes in her medical history. She experienced anomic aphasia and left-sided headache starting one day before admission. She had no trauma. A few minutes after admission she suddenly became comatose, her breathing became superficial. Non-contrast CT revealed left sided fronto-parietal subdural and subarachnoid and intracerebral haemorrhage, and bleeding was also observed in the right pontine region. The patient had leucocytosis and hyperglycemia but normal hemostasis. After the subdural haemorrhage had been evacuated, the patient was transferred to intensive care unit. Sepsis developed. Echocardiography did not detect endocarditis. Neurological status, vigilance gradually improved. The rehabilitation process was interrupted by epileptic status. Control CT and CT angiography proved an aneurysm in the peripheral part of the left middle cerebral artery, which was later clipped. Histolo­gical examination excluded mycotic etiology of the aneu­rysm and “normal aneurysm wall” was described. The brain stem haemorrhage – Duret bleeding – was presumably caused by a sudden increase in intracranial pressure due to the supratentorial space occupying process and consequential trans-tentorial herniation. This case is a rarity, as the patient not only survived, but lives an active life with some residual symptoms.

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

Extraskeletal, intradural, non-metastatic Ewing’s sarcoma. Case report


Intracranial localization of Ewing’s sarcoma is considerably very rare. Herein, we present clinical and neuroimaging findings regarding a 4-year-old boy with intracranial Ewing’s sarcoma. He was born prematurely, suffered intraventricular haemorrhage, posthaemorrhagic hydrocephalus developed, and a ventriculoperitoneal shunt was inserted in the newborn period. The patient endured re­gular follow ups, no signs of shunt malfunction nor increased intracranial pressure were observed. The last neuroima­ging examination was performed at 8 months of age. Upon reaching the age of 4 years, repeated vomiting and focal seizures began, and symptoms of increased intracranial pressure were detected. A brain MRI depicted a left frontoparietal space-occupying lesion infiltrating the superior sagittal sinus. The patient underwent a craniotomy resulting in the total excision of the tumour. The histological examination of the tissue revealed a small round blue cell tumour. The diagnosis was confirmed by the detection of EWSR1 gene translocation with FISH (fluorescent in situ hybridization). No additional metastases were detected during the staging examinations. The patient was treated in accordance to the EuroEwing 99 protocol. Today, ten years onward, the patient is tumour and seizure free and has a reasonably high quality of life.