Lucie Tučková

Markedly asymmetric presentation in multiple system atrophy

BACKGROUND Multiple system atrophy (MSA) presents with fairly symmetrical, levodopa unresponsive parkinsonism and additional features like autonomic dysfunction, cerebellar and corticospinal tract involvement. Marked asymmetry in atypical parkinsonism suggests alternative diagnosis like Corticobasal syndrome (CBS). METHODS We describe five unusual cases, who presented initially with markedly asymmetric parkinsonism, rigid dystonic abnormal limb posturing and subsequently developed clinical and/or radiological features consistent with probable MSA-P. RESULTS Using the internationally accepted diagnostic criteria, the patients fulfilled the diagnostic criteria for probable MSA-P after 5 years from disease onset. Case 4 and 5 had characteristic MRI features and Case 2 was pathologically confirmed. CONCLUSIONS We use these cases to highlight that MSA-P MSA-P can present rarely with very marked asymmetry, dystonic limb and myoclonic jerks leading to a diagnosis of CBS at onset.

Unusual phenotype of pathologically confirmed progressive supranuclear palsy with autonomic dysfunction and cerebellar ataxia: Case report

Background:Based on the results of recent multicenter clinical–pathological studies, it seems that the clinical heterogeneity of progressive supranuclear palsy (PSP) is much broader than previously thought. We will report 2 cases of patients with unusual manifestation of pathologically confirmed PSP. Methods:Two female patients were diagnosed with the parkinsonian phenotype of multiple system atrophy (MSAP) according to current clinical diagnostic criteria at the ages of 55 and 60 years, respectively. The patients were followed up for the next 5 and 7 years. In both cases, a detailed neuropathological examination of the brain was conducted postmortem. Results:In the first case, the overall pathological picture corresponded with the diagnosis of 4R tauopathy. In the second case, the brain pathology corresponded with a combination of 4R tauopathy and neocortical amyloidopathy. Conclusion:Some of the main symptoms of MSA, such as cerebellar ataxia and orthostatic hypotension, are not rare parts of the clinical picture of PSP. PSP can thus be mistakenly diagnosed as MSA. In order to determine the most accurate clinical diagnosis of PSP, a revision of its current clinical diagnostic criteria seems appropriate.

Glioblastoma multiforme in patients with history of extracranial cancer: Case series

OBJECTIVES Significant progress in treatment strategies improves the expectations of patients with extracranial cancers. Metastases are the primary consideration in patients with cancer history. In the case of neurologic disorders, the patient should undergo brain MRI. A rationale is presented for surgery, whole-brain or stereotactic radiotherapy, or chemotherapy. Recently, we have encountered misdiagnosed primary malignant brain tumours in patients with oncologic history who had been admitted for surgery for brain metastases. The aim of our study is to evaluate the incidence of concurrent cancers, to assess the relationship between previous cancer staging and primary brain tumour evaluation as well as to determine treatment efficiency. METHODS From January 2007 to December 2011, we prospectively followed up patients with concurrent history of both extracranial cancer and subsequent glioblastoma multiforme. Information was collected on the clinical condition, imaging, history of extracranial cancer, previous and present surgical and oncologic procedures, and GBM histologic, cytogenetic, and molecular genetic investigations. RESULTS Five patients were recruited: three females and two males. The average patient age at the time of GBM diagnosis was 65.6 years. Three patients had a history of breast carcinoma, one of renal carcinoma and one of colorectal carcinoma. Following the diagnosis of carcinoma, three patients received chemotherapy and radiotherapy, one patient had radiotherapy alone, and one had no adjuvant therapy. In all the cases, surgery revealed primary GBM, with a standard occurrence of genetic abnormalities (Table 1). The average time from the diagnosis of extracranial cancer to that of GBM was 4 years. Four patients underwent chemoradiotherapy and one had palliative radiotherapy. Two patients completed oncotherapy and their OS was 27 months and 19 months, respectively. One patient had post-surgical progression of hemiparesis. One patient had pulmonary embolism during oncotherapy and one had paraplegia caused by a pathological fracture of vertebras T5 due to breast carcinoma metastases. The OS was 11.8 months (range 3-27 months). All the patients succumbed to GBM progression.

An adult multifocal medulloblastoma with diffuse acute postoperative cerebellar swelling: immunohistochemical and molecular genetics analysis

Medulloblastoma (MB), the most common malignant tumor typically affecting children, occurs only exceptionally in adults. Multifocal presentation of this malignancy in adulthood is even much rarer—only four cases with favorable postoperative course have been reported, so far. The study illustrates a very rare rapid postoperative clinical deterioration due to diffuse cerebellar swelling (DCS) in an adult multifocal MB (MMB). To the best of their knowledge, authors for the first time performed genetic analysis of MMB and demonstrated expression patterns of selected markers that put the patient within the sonic hedgehog (SHH) molecular subgroup and at least partially explain her unsatisfactory clinical course. Herein, authors summarized the relevant literature concerning this issue with the aim to determine features that would facilitate diagnosis and therapy of such a scarce clinical entity.

Progressive supranuclear palsy phenotype mimicking synucleinopathies

BACKGROUND Atypical parkinsonian syndromes are currently divided into two groups based on their pathological appearance: synucleinopathies and tauopathies. Based on recent clinico-pathological studies it is increasingly clear, that some pathological characteristics are shared by both groups. STUDY OBJECTIVE To describe two pathologically proven cases of tauopathy manifesting in vivo in two typical synucleinopathy phenotypes: multiple system atrophy and dementia with Lewy bodies. PATIENTS AND METHODS There were 67-year-old woman with a phenotype of multiple system atrophy and a 70-year-old man with a phenotype of dementia with Lewy bodies. The clinical diagnosis was based on the commonly used clinical diagnostic criteria. A detailed neuropathological examination of the brain was conducted post-mortem in both cases. RESULTS The overall pathological picture corresponded with a rare combination of two neurodegenerative entities: 4R tauopathy (meeting the diagnostic criteria for typical progressive supranuclear palsy) and neocortical stage of Alzheimers disease. CONCLUSION The interesting feature in both our cases was the presence of dual pathology: diffuse tauopathy and Alzheimers pathology. We believe, that our two unique cases should serve as an evidence that tauopathies such as CBS and PSP might mimic practically anything from the family of atypical parkinsonian syndromes, particularly when another concomitant neurodegenerative disease is present.

IDH Mutation Analysis in Glioma Patients by CADMA Compared with SNaPshot Assay and two Immunohistochemical Methods

Mutations in IDH1/2 genes are a marker of good prognosis for glioma patients, associated with low grade gliomas and secondary glioblastomas. Immunohistochemistry and Sanger sequencing are current standards for IDH1/2 genotyping while many other methods exist. The aim of this study was to validate Competitive amplification of differentially melting amplicons (CADMA) PCR for IDH genotyping by comparison with SNaPshot assay and two immunohistochemical methods. In our study, 87 glioma patients (46 from Olomouc and 41 from Ostrava) were analyzed. IDH1/2 mutations in native bioptical samples were analyzed at DNA level by CADMA and SNaPshot while IDH1 mutations in FFPE samples were analyzed at protein level by two IHC methods. CADMA PCR sensitivity for IDH1 was 96.4% and specificity 100% for 86 concluded samples. SNaPshot assay sensitivity was 92.9% and specificity of 100% for 85 concluded samples. IHC in the laboratory no. 2 reached sensitivity 85.7% and specificity 100% for 86 concluded samples. IHC in the laboratory no. 4 reached sensitivity of 96.4% and specificity of 79.7% in 74 concluded samples. Only one IDH2 mutation was found by SNaPshot while CADMA yielded false negative result. In conclusion, CADMA is a valid method for IDH1 p.(R132H) testing with higher sensitivity than SNaPshot assay. Also, molecular genetic methods of IDH1 testing from native samples were more robust than IHC from FFPE.