Cowden syndrome and the associated Lhermitte-Duclos disease--Case presentation.

We report a patient with features of Cowden syndrome (CS). A 35-year old woman has been suffering from headache, vertigo and mild imbalance since 2 years. Examination showed subtle mucocutaneous lesions: papillomatous papules on the gingival mucosa, a few verrucous acral skin lesions and macrocephaly. Magnetic resonance imaging (MRI) revealed a tumor of the left cerebellar hemisphere with "tiger-striped" pattern on T2-weighted image (T2WI), typical of Lhermitte-Duclos disease (LDD)--one of the pathognomonic but infrequent features of CS. A pathogenic de novo heterozygous PTEN mutation: c.49C>T variant has been identified in exon 1 of the PTEN gene by sequencing.

Subtelomeric rearrangements in Polish subjects with intellectual disability and dysmorphic features.

Fluorescent in situ hybridization (FISH) was performed in 76 patients referred to our department because of intellectual disability and dysmorphic features that can be related to subtelomeric microaberrations. In all the patients, conventional cytogenetic methods revealed normal karyotype. Four (5.3%) subtelomeric rearrangements were detected by FISH: 2 subtelomeric 1p36 deletions, an unbalanced translocation involving chromosomes 1 and 12 with 1p36 deletion, and a de novo balanced translocation involving chromosomes 19 and 22. Thus, 3 cases of 1p36 subtelomeric deletion were found (3.95%). To confirm subtelomeric rearrangements in 2 patients, comparative genomic hybridization (CGH) was applied. Moreover, 3 cases of polymorphism without phenotypic effects were found: in 2 patients, the polymorphism involved the long arm of chromosome 2 (maternal derivative in both patients), while in the third patient, a polymorphism of the long arm of chromosome 7 was diagnosed. The latter polymorphism was also found in the patient's mother and grandfather.

The level of chemokine CXCL5 in the cerebrospinal fluid is increased during the first 24 hours of ischaemic stroke and correlates with the size of early brain damage.

Inflammation is an important feature of the pathophysiological response to ischaemic stroke. The ischaemic brain-invading leukocytes, neutrophils in particular, contribute to the exacerbation of tissue injury in stroke. Chemokines are a growing family of proteins performing chemotactic activity on selective leukocyte subpopulations. Chemokines are broadly divided into two major subfamilies on the basis of the arrangement of the two N-terminal cysteine residues, CXC and CC, depending on whether the first two cysteine residues have an amino acid between them (CXC) or are adjacent (CC). CXC chemokines possessing, close to the N terminus, the amino acid sequence glutamic acid-leucine-arginine (ELR motif) specifically act on neutrophils. CXCL5 is one of the ELR-expressing CXC chemokines and is a potent neutrophil attractant and activator. The objective of the study was to detect CXCL5 levels in the cerebrospinal fluid (CSF) and sera of stroke patients and to investigate the relation between these levels and the volume of brain computed tomography (CT) hypodense areas representing early ischaemic lesions. A total of 23 ischaemic stroke patients were studied. CSF and blood sampling and brain CT were performed within the first 24 hours of stroke. The control group consisted of 15 patients with tension headache. CXCL5 levels were determined by the ELISA method. CSF CXCL5 levels in stroke patients were significantly higher in comparison with the control group (38.2 +/- 18.4 pg/ml vs. 18.7 +/- 8.2 pg/ml; p < 0.001). No significant differences in serum CXCL5 levels were found between the stroke patients and the control group. CSF CXCL5 levels correlated positively with the volume of early brain CT hypodense areas (p < 0.0001). The results suggest that CXCL5 may play a role in the inflammatory reaction during the early phase of ischaemic stroke.

Interleukin-18 in acute ischaemic stroke patients.

As proinflammatory cytokines released during ischaemia are detrimental to the brain, the study aimed to evaluate serum interleukin-18 (IL-18) levels in stroke patients and to investigate the relation between these and epidemiological and clinical data. The study comprised 23 ischaemic stroke patients and 15 controls. Blood sampling for IL-18 determination and for chemistry, and brain CT were performed within 24 h of stroke, while neurological stroke severity and functional disability were estimated, respectively, with the Scandinavian stroke scale (SSS) and Barthel index (BI) within the same interval and two weeks later. There were higher serum IL-18 levels in stroke patients. These correlated with erythrocyte sedimentation rate (ESR), brain CT hypodense area volumes, and SSS and BI scores calculated at both studied times. Moreover, IL-18 levels were higher in patients with non-lacunar stroke subtype than in those with lacunar strokes. The results suggest that IL-18 is involved in stroke-induced inflammation and that initial serum IL-18 levels may be predictive of stroke outcome.

sPECAM-1 in serum and CSF of acute ischaemic stroke patients.

OBJECTIVES: As platelet endothelial cell adhesion molecule-1 (PECAM-1) is one of key mediators of transendothelial migration of leucocytes during inflammation, and inflammatory reaction is observed in cerebral ischaemia, we decided to determine the levels of soluble PECAM-1 (sPECAM-1) in serum and cerebrospinal fluid (CSF) of patients with acute stroke. MATERIAL AND METHODS: Twenty-three patients with first-ever in a lifetime completed ischaemic stroke have been studied. CSF and blood samples were obtained within 24 h of the onset of stroke and the levels of sPECAM-1 in serum and CSF were quantified by ELISA. RESULTS: Stroke patients displayed statistically significant higher levels of sPECAM-1 in sera and CSF in comparison with control group. The levels were significantly higher in serum than in CSF, correlated between each other, and CSF sPECAM-1 fraction was blood-derived. CONCLUSION: Our results indirectly suggest that PECAM-1 may play a role in the pathophysiological events during early phase of ischaemic stroke.

Early TNF-alpha levels correlate with ischaemic stroke severity.

OBJECTIVES: The study aimed to evaluate the levels of an important proinflammatory cytokine tumour necrosis factor-alpha (TNF-alpha) in cerebrospinal fluid (CSF) and serum in acute stroke and to study the relation between those and the neurological stroke severity and functional disability. MATERIAL AND METHODS: The investigations comprised 23 ischaemic stroke patients. CSF and blood samples were obtained 24 h after the onset of stroke, and stored until analysis. Patients were examined according to Scandinavian Stroke Scale (SSS) and to Barthel Index (BI). RESULTS: The patients displayed statistically significant high levels of TNF-alpha in CSF and sera within the first 24 h of stroke. These correlated significantly with SSS and BI scores calculated within the same interval, and 1 and 2 weeks later. CONCLUSION: Our results suggest the involvement of TNF-alpha in mechanisms of early stroke-induced inflammation and a predictive value of the initial TNF-alpha levels for the outcome of stroke.

Monocyte chemoattractant protein-1 is increased in the cerebrospinal fluid of patients with ischemic stroke.

BACKGROUND AND PURPOSE: Animal models of stroke have shown that focal cerebral ischemia results in an increased expression of several cytokines and chemokines that precedes leukocyte infiltration into ischemic lesions. The infiltrated leukocytes are thought to contribute to tissue injury in stroke. Monocyte chemoattractant protein-1 (MCP-1) may play an important role in monocyte/macrophage infiltration in stroke patients. METHODS: We studied MCP-1 level in sera and the cerebrospinal fluid of 23 ischemic stroke patients 24 hours after the onset of neurological symptoms and compared the results with 15 control patients with tension headache. The MCP-1 level was determined by ELISA. RESULTS: There was a significant increase of cerebrospinal fluid MCP-1 level in the studied stroke patients in comparison with the control group. The serum level of MCP-1 did not differ from that of control patients. CONCLUSIONS: Our results suggest that MCP-1 may play a role in the inflammatory reaction during the early phase of ischemic stroke.

[Tumor necrosis factor alpha (TNF-alpha) in patients with ischemic stroke]. / Czynnik martwicy nowotworu alfa (TNF-alfa) u chorych z udarem niedokrwiennym mózgu.

Tumour necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine. Stroke induces a rapid increase in TNF-alpha levels within and around the focus of damaged brain. The aim of our study was to evaluate, whether patients with stroke differ from control patients in the concentrations of TNF-alpha in cerebrospinal fluid and serum. We studied TNF-alpha levels in cerebrospinal fluid and serum in 30 patients with stroke within 24 h after onset of neurological signs and in 15 patients of control group with the diagnosis of tension headache and neurasthenia. In patients with stroke the levels of TNF-alpha in the cerebrospinal fluid and serum were significantly higher in comparison with control group. The results of our study may suggest the overproduction of TNF-alpha during first twenty-four hours of stroke.

Tumour necrosis factor-alpha is increased in the cerebrospinal fluid and serum of ischaemic stroke patients and correlates with the volume of evolving brain infarct.

A growing body of evidence suggests the involvement of inflammatory mediators, including cytokines, in the development of ischaemic brain lesions. The aim of the present study was to investigate whether tumour necrosis factor-alpha (TNF-alpha), the proinflammatory cytokine, contributes to early pathophysiological mechanisms leading to brain damage as a consequence of acute stroke. We have studied TNF-alpha levels in cerebrospinal fluid (CSF) and serum in 23 stroke patients within the first 24 hours after ischaemic stroke, confirmed by computerized tomography of the brain (CT). The control group consisted of 15 patients with the diagnosis of tension headache and neurasthenia. In stroke patients the levels of TNF-alpha both in CSF and serum were significantly higher in comparison with the control group. The positive correlation between the levels of TNF-alpha in CSF and serum of the studied patients has been observed. Furthermore, a positive correlation between both TNF-alpha levels in CSF and serum and the volume of evolving brain infarct have been shown.

The levels of TNF-alpha in cerebrospinal fluid and serum do not correlate with the counts of the white blood cells in acute phase of ischaemic stroke.

Stroke-induced inflammatory reaction, which leads to invasion of leukocytes into the evolving brain infarct, seems to play a key role in the deterioration of brain ischaemic impairment. We have studied CSF and serum levels of tumour necrosis factor-alpha (TNF-alpha), the potent proinflammatory cytokine, and peripheral white blood cells (WBC) counts in patients within the first 24 hours of ischaemic stroke. TNF-alpha levels in CSF and serum as well as WBC counts were increased. There was no correlation between TNF-alpha levels either in CSF and serum or in WBC counts. The results of our study suggest that increased CSF TNF-alpha levels may represent acute intracerebral inflammation in stroke, whereas elevated levels of TNF-alpha in serum may reflect the peripheral proinflammatory state as well as stroke-induced systemic inflammatory reaction. Increased CSF and serum TNF-alpha levels do not correlate with the elevation of WBC counts, suggesting that TNF-alpha overexpression observed in early phase of stroke is not dependent on increased total number of peripheral leukocytes.

[Clinical picture of spinocerebellar ataxia type I (SCA1)]. / Obraz kliniczny bezladu rdzeniowo-mózdzkowego typu I (SCA1).

Spinocerebellar ataxia is a group of diseases with autosomal dominant inheritance heterogenous both clinically and genetically. So called dynamic mutations underlie most these nosological units. The clinical patterns of various SCA types have not yet been defined completely. The purpose of the present report was description of the typical symptoms and signs of type 1 SCA. Seventeen patients from 13 families (M-2, F-15) were studied clinically in detail. The diagnosis was confirmed by DNA analysis. The assessment included neurological status, cognitive functions, the results of EEG, EMG, SEP, VEP, BAER and MRI examinations. The pedigrees indicated autosomal dominant inheritance pattern. The mean age at onset was 35.5 +/- 6.8 years (range 23-45 years) and it suggested negative correlation with the number of CAG repetitions. Cerebellar syndrome limb and truncal, ataxia and dysarthria was present in all cases. Six patients had nystagmus, 3 had slow saccades, 2 had gaze limitation upward, and lateral and 6 had dysphagia. Signs of pyramidal system involvement were found in 10 cases, one had athetotic movements, one had orthostatic hypotension. Two patients had dementia features, 9 had some decline of intellectual functions, mainly with difficulties of memorization, learning and concentration. In 16 cases MRI demonstrated vermis atrophy and atrophy of cerebellar hemispheres, 14 had fourth ventricle dilatation, 8 had flattening of pons base, 8 had narrowing of cervical spinal cord, 8 had dilated CSF spaces over frontal lobes and in 6 cases lateral ventricles were dilated. Electrophysiological peripheral nervous system investigations showed in 16 cases long-standing damage to the motor and sensory peripheral neurons at the level of nerve trunks, more pronounced in sensory nerves. In 13 cases peripheral neuron damage was subclinical. SEP showed in all patients disturbed function of ascending sensory pathways at peripheral and spinocortical levels.

Contribution of tumor necrosis factor alpha to the pathogenesis of stroke.

Tumor necrosis factor alpha (TNF-alpha) is a protein of a cellular origin belonging to a group of proinflammatory cytokines. A rapid overproduction of TNF-alpha in a cerebral post-ischemic inflammatory response leads to the stimulation of adhesive molecules expression with subsequent accumulation of leukocytes in the ischemic focus, which is preceded by their adhesion and migration. The TNF-alpha proinflammatory activity results mainly in extending the area of the brain infarct, which brings about negative clinical implications. Being the final morphological effect of ischemic stroke, TNF-alpha appears also to contribute to neuronal necrosis by its involvement in the process of apoptosis as well as in the death of neurons. The present study describes and discusses mainly the contribution of TNF-alpha to the formation of ischemic focus in the brain.

[Prenatal diagnosis: an attempt at evaluation of effectiveness and risk based on the experience of one center]. / Badania prenatalne--próba oceny efektywosci i ryzyka na podstawie materialu jednego osrodka.

We present the results of prenatal diagnosis in 2241 women carried out in one centre in the period 1985-1994. Indications were cytogenetic in 84% of the cases, of those in 77% it was maternal age 35 years and over. The second most frequent indication was open neural tube defect in a previously born child (7.5%). Abnormal results of prenatal tests in whole material were obtained in 60 cases (2.4%); in 47 cases this was chromosomal aberration. Abnormal result of prenatal test did not necessarily mean selective termination of pregnancy. In 17.5% of chromosomal fetal aberrations pregnancy was continued (it concerned mostly aberrations involving sex chromosomes). The risk of prenatal diagnosis (miscarriage due to the procedure) according to our estimation was between 0.3 and 0.6% of the tested pregnancies. Sociological analysis of the tested group showed clearly that women with better education (secondary and higher level) in Poland have much better access to prenatal diagnosis. Most of the tested woman (72%) considered a prenatal test a sine qua non condition of their procreation.

[Autosomal dominant spinocerebellar ataxia]. / Autosomalny dominujacy bezlad rdzeniowo-mózdzkowy.

The modern classification is presented based on genetic criteria of the group of degenerative nervous system diseases inherited as autosomal dominant trait and called collectively spinocerebellar ataxia (SCA). They belong mostly to the class of diseases of similar mutation mechanism in which amplification is present of the trinucleotide sequence (CAG)n. Clinical picture and neuropathological changes in various SCA types are compared.

[Juvenile form of Huntington's disease--diagnostic problems]. / Dziecieca i mlodziencza postac choroby Huntingtona--problemy diagnostyczne.

Variability of clinical manifestation is an important feature of Huntington's disease (HD). It is due to the high instability of CAG sequences within a coding region of IT15 gene. We present five pedigrees in which apart from the adult form of HD the juvenile form of the disease affected some of the patients--as a result of genetic anticipation. Molecular analysis confirmed the well known fact that anticipation, which manifests itself by earlier onset of the disease in the subsequent generations, is strongly correlated with the degree of amplification of (CAG)n repeats in IT15 gene. An interesting feature of the presented data is the fact, that expansion of CAG repeats occurred not only at the paternal but also at the maternal transmission of the mutation. Some children in the presented HD pedigrees presented other neurological disturbances which could be suspected of HD; a molecular analysis revealing normal number of CAG repeats, enabled us to avoid misdiagnosis. The presented data provide evidence that clinical diagnosis of HD, particularly in cases with not very characteristic clinical picture--is not possible without DNA analysis--even in the families undoubtfully affected with the disease.

[Germline mosaicism in a family with Duchenne muscular dystrophy]. / Mozaikowosc gonad w rodzinie z dystrofia miesniowa Duchenne'a.

In families with Duchenne/Becker muscular dystrophy, DNA analysis allows direct detection of the sex-linked dystrophy gene mutation. The detection of two alleles (heterozygous) in the region of a deletion in an affected son, excludes the mother having the same deletion. However, it is known that in isolated cases of this disease there is a risk of mosaicism, resulting in genetically different cell lines in the same or different tissues. Because of this consideration, in a subsequent pregnancy, prenatal diagnosis was performed on the mother, who was previously excluded from carrying the deletion based on DNA analysis of blood leukocytes. The examination showed the sex of the foetus to be male, and notably, a deletion identical to that in the ill boy was detected. This indicates that the patient has a germ cell deletion (germline mosaicism).

[Detecting carriers of a deletion in the dystrophin gene in families with a single case of Duchenne/Becker muscular dystrophy]. / Wykrywanie nosicielek delecji w genie dystrofiny w rodzinach z izolowanym przypadkiem dystrofii miesniowej Duchenne'a/Beckera.

A search for female mutation carriers was performed in 40 families with an isolated case of Duchenne/Becker muscular dystrophy due to a deletion in the dystrophin gene. Intragenic restriction sites and microsatellite sequences (CA repeats) were analysed in females possible carriers of the deletion. Application of this approach enabled us the detection of the deletion in 19 females in 9 families and exclusion of the deletion in 41 females in 23 families. The results of DNA analysis in the remaining 8 families were not informative.

[Carrier's detection in families affected by Duchenne/Becker muscular dystrophy in which DNA from affected individuals is not available]. / Okreslanie nosicielstwa mutacji wywolujacej dystrofie miesniowa Duchenne'a/Beckera w rodzinach z niedostepnym DNA chorego.

Carrier/noncarrier status of the mutated dystrophin gene was established in 9 females from four families with Duchenne/Becker muscular dystrophy, in which samples of DNA from the affected members were not available. Analysis of extra- and intragenic polymorphic segments of the dystrophin gene enabled identification of two female carriers and exclusion of carriership in four females. In three cases the results were not informative because of recombination in the analysed segment of the gene.