Haemorrhagic transformation in ischaemic stroke is more frequent than clinically suspected - A neuropathological study.

OBJECTIVES: The vast majority of literature on the frequency of the haemorrhagic transformation of ischaemic stroke is based on imaging studies. The purpose of the present study was to assess the added value of autopsy and neuropathological analysis in a neurology centre with emphasis on acute stroke care. METHODS: We retrospectively analysed the findings of 100 consecutive brain autopsies followed by detailed clinical correlation. RESULTS: The clinical diagnosis was confirmed by neuropathology in every patient with intracerebral haemorrhage and with non-cerebrovascular neurological disorders (e.g. primary tumours, metastases, infections). At admission 64 patients (age 62years, SD 6.5) were diagnosed with acute ischaemic stroke. In 10 of these patients (16%) haemorrhagic transformation was diagnosed clinically by a second CT. In 24 cases (38%) haemorrhagic transformation was detected only at autopsy. The distribution of haemorrhagic transformation in our material was the following: small petechiae in 26.5%, more confluent petechiae in 29.4%, ≤30% of the infarcted area with some mild space-occupying effect in 29.4% and >30% of the infarcted area with significant space-occupying effect or clot remote from infarcted area in 14.7%. Most of the PH1-2 transformations developed in thrombolysed patients and all of the PH2 type transformations were diagnosed already clinically. CONCLUSIONS: We demonstrated that haemorrhagic transformation is frequent and often undiscovered in vivo. Our findings underline the importance of post-mortem neuropathological examination also in the era of advanced imaging techniques and prove that autopsy is the ultimate yardstick of our diagnostic and therapeutic efforts. The high number of haemorrhagic transformations diagnosed only after death is an important novel finding with clinical implications.

New prognostic score for the prediction of 30-day outcome in spontaneous supratentorial cerebral haemorrhage.

AIMS: The purpose of the present study was to evaluate predictors of outcome in primary supratentorial cerebral haemorrhage. Furthermore, we aimed to develop a prognostic model to predict 30-day fatality. METHODS: We retrospectively analyzed a database of 156 patients with spontaneous supratentorial haemorrhage to explore the relationship between clinical and CT characteristics and fatal outcome within 30 days using multiple logistic regression analysis. The analyzed factors included volumetric data assessed by neuropathological and CT volumetry. A second CT scan in survivors or neuropathological ABC/2 volumetry in nonsurvivors was used along with the baseline CT to assess the growth index of haematoma. RESULTS: Systolic blood pressure, serum potassium and glucose levels, platelet count, absolute and relative haematoma volumes, and presence and size of intraventricular haemorrhage statistically significantly predicted the fatal outcome within 30 days. Based on our results we formulated a six-factor scoring algorithm named SUSPEKT to predict outcome. CONCLUSIONS: After validation the SUSPEKT score may be applicable in general clinical practice for early patient selection to optimize individual management or for assessment of eligibility for treatment trials.

[Molecular genetics of familial tumour syndromes of the central nervous system]. / A központi idegrendszert érinto családi daganatszindrómák molekuláris háttere.

Although most of the central nervous system tumours are sporadic, rarely they are associated with familial tumour syndromes. These disorders usually present with an autosomal dominant inheritance and neoplasia develops at younger age than in sporadic cases. Most of these tumours are bilateral, multiplex or multifocal. The causative mutations occur in genes involved in cell cycle regulation, cell growth, differentiation and DNA repair. Studying these hereditary cancer predisposition syndromes associated with nervous system tumours can facilitate the deeper understanding of the molecular background of sporadic tumours and the development of novel therapeutic agents. This review is an update on hereditary tumour syndromes with nervous system involvement with emphasis on molecular genetic characteristics and their clinical implications.

Inclusion body myositis - pathomechanism and lessons from genetics.

Inclusion body myositis is a rare, late-onset myopathy. Both inflammatory and myodegenerative features play an important role in their pathogenesis. Overlapping clinicopathological entities are the familial inclusion body myopathies with or without dementia. These myopathies share several clinical and pathological features with the sporadic inflammatory disease. Therefore, better understanding of the genetic basis and pathomechanism of these rare familial cases may advance our knowledge and enable more effective treatment options in sporadic IBM, which is currently considered a relentlessly progressive incurable disease.

Poly(ADP-ribose) polymerase-1 (PARP1) and p53 labelling index correlates with tumour grade in meningiomas.

Meningiomas are one of the most frequent intracranial tumours, with 13 histological types and three grades according to the 2007 WHO Classification of Tumours of the Central Nervous System. p53, as one of the most potent tumour suppressor proteins, plays a role in nearly 50% of human tumours. Poly(ADP-ribose) polymerase (PARP) is a DNA repair enzyme with high ATP demand. It plays a role in apoptosis by activating an apoptosis inducing factor, and in necrosis by consuming NAD+ and ATP. Only PARP1 has been investigated in detail in tumours out of the 17 members of the PARP superfamily; however, its role has not been studied in meningiomas yet. The aim of this study was to determine the role of p53 and PARP1 in meningiomas of different grade and to establish whether there is any correlation between the p53 and PARP1 expression. Both PARP1 and p53 have been expressed in all examined meningiomas. PARP1 labelled grade II tumours with a higher intensity as compared to grade I and III neoplasms, respectively. An increased p53 expression was noted in grade III meningiomas. There was no statistical correlation between p53 and PARP1 expression. Our data indicate that both PARP1 and p53 activation is a feature in meningiomas of higher grade, PARP1 overexpression being an early, whereas p53 overexpression, a late event in tumour progression.

[The diagnosis of herpes encephalitis--a case-based update]. / A herpesencephalitis diagnosztikájáról egy esetismertetés kapcsán.

Herpes simplex virus encephalitis (HSVE) is a rare and life-threatening infection. The clinical signs are diverse and often misleading regarding the aetiology. However, focal seizure with fever and typical CT/MRI finding should always raise the possibility of HSVE as early diagnosis and antiviral therapy is crucial. Before the advent of molecular techniques and high-tech imaging histological examination from multiple brain biopsies were often necessary. Although nowadays PCR and other molecular methods may provide an aetiological diagnosis some cases need neuropathological verification. Due to the high IgG seropositivity rate in the population the plasma IgG titer is not diagnostic and elevation of its plasma level requires several weeks. We report the case of a 25-years old male patient who initially presented with epileptic seizures. There was no final diagnosis and no causal treatment in the district general hospital. The patient was admitted to our institution in comatose state on day 9; the initiated diagnostic tests and therapy could not save the patient who died next day. The autopsy and subsequent neuropathological examination revealed HSVE. We present a flowchart on diagnostic work-up and special techniques to aid diagnosis in suspected viral encephalitis.

[Diagnosis of cerebral hemorrhage before the era of computed tomography]. / A cerebrális állományvérzés diagnosztikája a komputertomográfia korszaka elott.

INTRODUCTION: During the past decades there has been a great progress in neuroimaging methods. Cranial computed tomography is part of the daily routine now and its use allows a fast diagnosis of parenchymal hemorrhage. However, before the availability of computed tomography the differentiation between ischemic and hemorrhagic stroke was based on patient history, physical examination, percutan angiography and cerebrospinal fluid sampling, and the clinical utility could be evaluated by autopsy of deceased patients. AIM: The authors explored the diagnostic performance of cerebrospinal fluid examination for the diagnosis of ischemic and hemorrhagic stroke. METHOD: Data of 200 deceased stroke patients were retrospectively evaluated. All patients had liquor sampling at admission and all of them had brain autopsy. RESULTS: Bloody or yellowish cerebrospinal fluid at admission had a positive predictive value of 87.5% for hemorrhagic stroke confirmed by autopsy, while clear cerebrospinal fluid had positive predictive value of 90.7% for ischemic stroke. Patients who had clear liquor, but autopsy revealed hemorrhagic stroke had higher protein level in the cerebrospinal fluid, but the difference was not statistically significant (p = 0.09). CONCLUSIONS: The results confirm the importance of pathological evaluation of the brain in cases deceased from cerebral stroke. With this article the authors wanted to salute for those who contributed to the development of the Hungarian neuropathology. In this year we remember the 110th anniversary of the birth, and the 60th anniversary of the death of professor Kálmán Sántha. Professor László Molnár would be 90 years old in 2013.

Neuronal caspase-3 and PARP-1 correlate differentially with apoptosis and necrosis in ischemic human stroke.

Apoptotic cell death contributes to neuronal loss in the penumbral region of brain infarction. Activated caspase-3 (ACA-3) cleaves proteins including poly(ADP-ribose) polymerase-1 (PARP-1) important in DNA repair, thus promoting apoptosis. Overactivation of PARP-1 depletes NAD(+) and ATP, resulting in necrosis. These cell death phenomena have been investigated mostly in experimental animals. We studied an autopsy cohort of 13 fatal ischemic stroke cases (symptoms 15 h to 18 days) and 2 controls by immunohistochemical techniques. The number of PARP-1 immunoreactive neurons was highest in the periinfarct area. Nuclear PARP-1 correlated with increasing neuronal necrosis (P = 0.013). Cytoplasmic PARP-1 correlated with TUNEL in periinfarct and core areas (P = 0.01). Cytoplasmic cleaved PARP-1 was inversely correlated with increasing necrotic damage (P = 0.001). PAR-polymers were detected in neurons confirming enzymatic activity of PARP-1. Cytoplasmic ACA-3 correlated with death receptor Fas (r (s) = 0.48; P = 0.005). In conclusion, the confirmation of the same pathways of cell death than previously described in experimental animal models encourages neuroprotective treatments acting on these mediators also in human stroke.