Age- and sex-related characteristics of tonic GABA currents in the rat substantia nigra pars reticulata.

Previous studies have shown that the pharmacologic effects of GABAergic drugs and the postsynaptic phasic GABAAergic inhibitory responses in the anterior part of the rat substantia nigra pars reticulata (SNRA) are age- and sex-specific. Here, we investigate whether there are age- and sex-related differences in the expression of the δ GABAA receptor (GABAAR) subunit and GABAAR mediated tonic currents. We have used δ-specific immunochemistry and whole cell patch clamp to study GABAAR mediated tonic currents in the SNRA of male and female postnatal day (PN) PN5-9, PN11-16, and PN25-32 rats. We observed age-related decline, but no sex-specific changes, in bicuculline (BIM) sensitive GABAAR tonic current density, which correlated with the decline in δ subunit in the SNRA between PN15 and 30. Furthermore, we show that the GABAAR tonic currents can be modified by muscimol (GABAAR agonist; partial GABACR agonist), THIP (4,5,6,7-tetrahydroisoxazolo (5,4-c)pyridin-3-ol: α4ß3δ GABAARs agonist and GABACR antagonist), and zolpidem (α1-subunit selective GABAAR agonist) in age- and sex-dependent manner specific for each drug. We propose that the emergence of the GABAAR-sensitive anticonvulsant effects of the rat SNRA during development may depend upon the developmental decline in tonic GABAergic inhibition of the activity of rat SNRA neurons, although other sex-specific factors are also involved.

[Meningoencephalitis caused by Toscana virus in Czech travelers returning from the Mediterranean]. / Meningoencefalitidy zpusobené virem Toscana u ceských cestovatelu po návratu ze Stredomorí.

Presented are case studies of 3 patients with aseptic meninogencephalitis occurring after returning from the Mediterranean tourist regions. None of the infectious agents common in aseptic neuroinfections in the Czech Republic was detected in the patients. Serological tests showed that in each case, the illness was caused by Toscana virus, a phlebovirus belonging to the family Bunyaviridae. The virus is transmitted by tiny biting insects of the genus Phlebotomus commonly present in the Mediterranean area. The course of the disease was mild to moderate and all the patients recovered without sequelae. These case reports document the fact that this arbovirus should be considered in the differential diagnosis of patients with aseptic neuroinfections returning from endemic areas of this virus.

From Morris Water Maze to computer tests in the prediction of Alzheimer's disease.

BACKGROUND: Spatial navigation performance in the Hidden Goal Task (HGT), a real-space human analogue of the Morris Water Maze, can identify amnestic mild cognitive impairment (aMCI) patients with memory impairment of the hippocampal type, a known indicator of incipient Alzheimer's disease (AD). OBJECTIVE: Contrast results from computer versus real-space versions of the HGT. METHODS: A total of 42 aMCI patients were clinically and neuropsychologically classified into: (1) memory impairment of the hippocampal type--the hippocampal aMCI (HaMCI; n = 10) and (2) isolated retrieval impairment--the nonhippocampal aMCI (NHaMCI; n = 32). Results were compared to the control (n = 28) and AD (n = 21) groups. RESULTS: The HaMCI group, although similar to the NHaMCI group with respect to overall cognitive impairment, performed poorer on the computer version of the HGT and yielded parallel results to the real-space version. The two versions were strongly correlated. CONCLUSIONS: Both versions of the HGT can reliably identify aMCI with pronounced memory impairment of the hippocampal type. The computer version of the HGT may be a useful, relatively inexpensive screening tool for early detection of individuals at a high risk of AD.

A 71-nucleotide deletion in the periaxin gene in a Romani patient with early-onset slowly progressive demyelinating CMT.

BACKGROUND: Mutations in the periaxin (PRX) gene cause autosomal recessive demyelinating neuropathy Charcot-Marie-Tooth (CMT) type 4F. To date, 10 non-sense or frameshift PRX mutations have been reported in patients with early-onset neuropathy and further disease course consistent with either Dejerine-Sottas neuropathy or slow-progressive demyelinating CMT. METHODS: We sequenced 59 patients from 55 Czech families including four unrelated patients of Romani (Gypsy) origin with early-onset CMT displaying decreased nerve conduction velocities. RESULTS: We identified a novel homozygous mutation c.3286_3356del71 (K1095fsX18) in one Romani patient showing very slow disease progression. Amongst non-Romani Czech CMT patients, PRX mutations have been proven to be very rare.

EFNS guideline on the management of community-acquired bacterial meningitis: report of an EFNS Task Force on acute bacterial meningitis in older children and adults.

Acute bacterial meningitis (ABM) is a potentially life-threatening neurological emergency. An agreed protocol for early, evidence-based and effective management of community-acquired ABM is essential for best possible outcome. A literature search of peer-reviewed articles on ABM was used to collect data on the management of ABM in older children and adults. Based on the strength of published evidence, a consensus guideline was developed for initial management, investigations, antibiotics and supportive therapy of community-acquired ABM. Patients with ABM should be rapidly hospitalized and assessed for consideration of lumbar puncture (LP) if clinically safe. Ideally, patients should have fast-track brain imaging before LP, but initiation of antibiotic therapy should not be delayed beyond 3 h after first contact of patient with health service. In every case, blood sample must be sent for culture before initiating antibiotic therapy. Laboratory examination of cerebrospinal fluid is the most definitive investigation for ABM and whenever possible, the choice of antibiotics, and the duration of therapy, should be guided by the microbiological diagnosis. Parenteral therapy with a third-generation cephalosporin is the initial antibiotics of choice in the absence of penicillin allergy and bacterial resistance; amoxicillin should be used in addition if meningitis because of Listeria monocytogenes is suspected. Vancomycin is the preferred antibiotic for penicillin-resistant pneumococcal meningitis. Dexamethasone should be administered both in adults and in children with or shortly before the first dose of antibiotic in suspected cases of Streptococcus pneumoniae and H. Influenzae meningitis. In patients presenting with rapidly evolving petechial skin rash, antibiotic therapy must be initiated immediately on suspicion of Neisseria meningitidis infection with parenteral benzyl penicillin in the absence of known history of penicillin allergy.

Two cases of improvement of smooth pursuit eye movements after selective posterior rhizotomy.

OBJECTIVE: Selective posterior rhizotomy (SPR) represents a standard neurosurgical approach in the treatment of spasticity in children with cerebral palsy (CP). Beside the reduction of spasticity in lower limbs, SPR may have suprasegmental effects, considerably above the surgery site. In this communication, we report on the improvement of smooth pursuit eye movements (SPEM) in two children after SPR. MATERIAL AND METHODS: Four children with CP underwent SPR. Eye movements were registered by infrared video-oculography before and after the surgery. RESULTS: The analysis of SPEM showed the improvement of the correlation coefficient of the eye response to the stimulus after SPR in two subjects. Improvement of SPEM performance was largely due to suppression of spontaneous fixation nystagmus. CONCLUSION: SPR may lead to the improvement of SPEM in children with CP. The influence of SPEM improvement on quality of life in a group of severely disabled nonambulant children with CP remains to be assessed.

GDAP1 mutations in Czech families with early-onset CMT.

Mutations in the ganglioside-induced differentiation associated protein-1 gene (GDAP1) cause autosomal recessive (AR) demyelinating or axonal Charcot-Marie-Tooth neuropathy (CMT). In order to establish the spectrum and frequency of GDAP1 mutations in Czech population, we sequenced GDAP1 in 74 Czech patients from 69 unrelated families with early-onset demyelinating or axonal CMT compatible with AR inheritance. We identified three isolated patients with GDAP1 mutations in both alleles. In one additional sporadic and one familial case, the second pathogenic mutation remained unknown. Overall, we detected two different mutations, a novel R191X nonsense and a L239F missense mutation. L239F previously described in a German-Italian family is a prevalent mutation in Czech population and we give evidence for its common ancestral origin. All Czech GDAP1 patients developed involvement of all four limbs evident by the end of second decade, except for one isolated patient showing very slow disease progression. All patients displayed axonal type of neuropathy.

Antibody formation against beta-tubulin class III in response to brain trauma.

Brain trauma typically leads to neuronal damage and loss. Assuming a transient autoimmune response to debris of the damaged neurones, we have monitored serum titres of IgG and IgM antibodies to beta-tubulin class III (betaTcIII), which is almost exclusively found in neuronal cytoskeletons. In 15 out of 18 patients, the peak of the IgG or IgM antibody titre appeared in the serum within 3 weeks of a brain trauma.

Molecular and microscopical evidence of Ehrlichia spp. and Borrelia burgdorferi sensu lato in patients, animals and ticks in the Czech Republic.

We report moderately severe cases of human ehrlichiosis and a lethal one caused by human granulocytic Ehrlichia, the HGE agent, closely related to Ehrlichia phagocytophila and Ehrlichia equi. Their vector is the Ixodes ricinus tick, which also transmits Borrelia burgorferi sensu lato in central, west and east regions of the Czech Republic. The diagnosis was established by PCR with sequence analysis of the genes encoding 16S rRNA of Ehrlichia and with reverse hybridization by using enzyme linked immunosorbent assay with different covalently coupled probes to the activated plate. Ten out of 47 patients and 10 huntsmen were PCR positive and 7 of them seroconverted to the HGE. Coinfection of Ehrlichia phagocytophila with Borrelia burgdorferi sensu lato was detected in 3 patients. Ehrlichia spp., the HGE agent, was isolated and propagated only from one patient in the HL-60 promyelocytic cell line. The maintenance of Ehrlichia in culture and in patients was assayed also by immunocytological staining and electron microscopy. Sequence or hybridization analysis of PCR results in different wild mammals and birds showed significant sources of Ehrlichia fagocytophila in nature. Three variants of E. phagocytophila in wild roe deer and boars, as well as for the first time in birds, have been described. Cultures from the blood of horses, and from the spleen and kidney specimens of roes and boars, PCR positive for Ehrlichia spp., displayed a disappearing level of the pathogen or contamination with other bacteria.

[A neurologist's views on cellular and gene therapy in nervous system diseases]. / Pohled neurologa na bunecnou a genovou lécbu chorob nervového systému.

Lesional impairment of the brain and spinal cord is a serious and usually irreversible disorder. There is only a small chance of functionally significant compensation of lesions. Neurons and glia are marked by the minimal regeneration. Though plasticity and adaptability represent important mechanisms, which can contribute to the compensation of structural and functional CNS disorders, irreversible structural and functional deficits may develop. Transplantation of various cells incl. neurons from fetal brain or transplantation of genetically modified cells was therefore proposed. Clear verification of this method by animal tests and by clinically controlled trials is a necessary condition. Its application is expected in atrophic-degenerative and vascular diseases of CNS, tumors, injuries, seizure, inflammatory and demyelinating diseases in which the replacement of neurons, glia and enhancement of their regeneration play the key role. Transplantation of embryonic stem cells, fetal neural cells, and haematopoietic stem cells introduced by stereotaxic, hematogenic or intrathecal procedure gets the attention. Bioethical problems and the possible contribution of this method based on experience with transplantation of fetal cells into basal ganglia of 3 patients with Parkinson's disease and haematopoietic stem cell transplantation in multiple sclerosis (n 1) are discussed.

Paraneoplastic opsoclonus-myoclonus syndrome associated with malignant fibrous histiocytoma: neuropathological findings.

Paraneoplastic syndromes related to soft tissue tumors are very uncommon and an association of paraneoplastic diseases with a malignant fibrous histiocytoma (MFH) has not been reported so far. Opsoclonus-myoclonus is a rare paraneoplastic nervous system syndrome, that was well documented in adult patients with neoplasms particularly of the lung and breast. A 77-year-old woman developed typical opsoclonus-myoclonus syndrome and rapidly progressed to coma. The opsoclonus and generalized myoclonus continued until the patient's death seven months later. An autopsy examination identified a pleomorphic MFH in the retroperitoneum without a metastatic spread. Microscopic examination of the cerebellum revealed an atrophy of the granular layer along with a marked patchy loss of Purkinje cells, and a loss of neurons in the cerebellar nuclei accompanied by distinct peridental demyelination and astrogliosis. A moderate loss of neurons and neuronal chromatolysis were observed also in the inferior olivary nuclei. However, the omnipause neurons of the nucleus raphe interpositus, that are supposed to be responsible for opsoclonus generation under pathological conditions, as well as ocular brain stem nuclei were all intact. We failed to prove the presence of known antineuronal anti-Yo, anti-Hu or anti-Ri autoantibodies in both serum and cerebrospinal fluid (CSF) of the patient. However, the confirmation of the intrathecal IgG synthesis by oligoclonal bands in CSF and the immunohistochemical detection of IgG deposits on membranes of Purkinje cells, neurons of cerebellar granular layer and in cerebellar nuclei in our case support the presumed autoimmune nature of the disease.

[Esophageal echocardiography in patients with cerebrovascular stroke and atrial fibrillation]. / Jícnová echokardiografie u nemocných s cévní mozkovou príhodou a fibrilací síní.

Atrial fibrillation is an important risk factor of embolization into the CNS. Thus affected patients should receive permanent anticoagulant therapy. Oesophageal echocardiography (TEE) can help our decision in patients with relative contraindications of anticoagulant therapy. TEE was performed in 52 patients with atrial fibrillation and cerebrovascular attack (CMP) with an ischaemic aetiology. Transthoracic echocardiography did not reveal the source of embolization. In 10% patients a thrombus was found in the appendage of the left atrium, in another 9% patients a spontaneous echocontrast was found in the left atrium (prethrombotic condition) and in 5% patients an open foramen ovale. The results indicate the highly probable etiology of embolization in patients with cerebrovascular attacks and atrial fibrillation. This supports the recommendation of absolute indication of anticoagulant treatment in patients with cerebrovascular attacks and atrial fibrillation.

[Proportion of tau protein to phosphorylated tau protein CSF levels in differential diagnosis of dementia]. / Bedeutung der Gesamt-tau- und Phospho-tau-Protein-Liquorspiegel in der Demenzdiagnostik.

BACKGROUND: The diagnosis of Creutzfeldt-Jakob disease (CJD) is based on typical clinical features and can be supported by detection of 14-3-3 protein in the CSF. The present study suggests the importance of investigating this ratio of total tau protein to phosphorylated tau protein in differentiating CJD from other dementias. Thirty-one patients with Alzheimer's disease (AD) or frontotemporal dementia and four with definitive diagnoses of CJD were included in the study. METHODS AND MATERIAL: Results from baseline investigations were compared with those from an age-matched cognitively controlled group with Bell's palsy. Tau protein, phosphorylated tau protein, and beta amyloid were analyzed using a commercially available enzyme-linked immunosorbent assay; 14-3-3 protein was assessed by Western blotting. RESULTS AND CONCLUSION: A distinctly high proportion of total tau protein to phosphorylated tau protein in CSF was found in all patients diagnosed with CJD, even in those with negative 14-3-3 protein blot results. In contrast, marker analysis in patients with Alzheimer's dementia revealed the highest CSF ratio of beta amyloid to phosphorylated tau protein levels. These proteins are important diagnostic biomarkers for CJD, especially in patients with negative 14-3-3 protein findings.

Transoesophageal echocardiography in patients with stroke and low risk of embolic etiology.

Transoesophageal echocardiography (TEE) is currently the gold standard in the diagnosis of cardiac sources of embolization and the frequently discussed question is whether all patients with suspected embolic stroke should be screened by TEE. Based on the results of transthoracic echocardiography (TTE), we determined the significance of TEE in patients with ischemic stroke with low risk of embolic etiology. We made a retrospective evaluation of TEE examination in the period from 1(st) January 2000 to 31(st) December 2003 in patients with ischemic stroke and sinus rhythm and normal left ventricular function. TEE examination was done in 159 patients. A quarter of the patients had pathological findings in the heart: left atrial thrombus in nine (5.7%), spontaneous echocontrast in left atrium in 14 (8.8%), patent foramen ovale in 16 (10%) and other findings in seven (4.4%) patients. The finding of the thrombus or echocontrast in the left atrium correlated with the size of the left atrium and it was proved in the patients with left atrium of size above 39 mm. On the contrary, patent foramen ovale was found in younger patients (70 vs. 59 years). Our results have shown that TEE is of low relevance to patients with a normal transthoracic echocardiogram.

Neuroborreliosis in an HIV-1 positive patient.

Simultaneous co-infections of Borrelia burgdorferi sensu lato and HIV-1 are rare events, with only six published cases. A case of acute neuroborreliosis with facial palsy, meningoradiculitis (Bannwarth's syndrome) in an HIV-1 positive individual is described. Diagnosis was confirmed by Western immunoblot analysis of serum and CSF and by proof of intrathecal production of antibodies against B. garinii. The patient was successfully treated with cefotaxime. In all published HIV+ cases, the course of borreliosis did not differ from that of the HIV negative population and the prognosis in properly treated patients was good.

Amygdalar volume and psychiatric symptoms in Alzheimer's disease: an MRI analysis.

OBJECTIVES: We measured the volumes of the amygdala to test the hypothesis that the reduction of amygdalar volume may be associated with psychiatric symptoms in Alzheimer's disease. MATERIALS AND METHODS: Twenty-seven patients underwent neuropsychological investigation including the assessment of general clinical severity by the Mini-Mental State Examination (MMSE) and Neuropsychiatric Inventory (NPI). All patients underwent magnetic resonance imaging (MRI) of the head, from which the volumes of the amygdalae were measured. The obtained values were compared with those of controls (n = 15). RESULTS: Patients with Alzheimer's dementia showed significant reduction in MRI volumetric measurements compared with controls. We found a significant correlation of MMSE score and absolute amygdala volume (r = 0.62, P < 0.01). Neither the absolute nor relative volume of the amygdala showed any correlation with NPI scores. CONCLUSIONS: The atrophy of the amygdala does not have a direct association with the existence of neuropsychiatric symptoms. MRI volumetry of the amygdala may be relevant as a marker of dementia severity in Alzheimer's disease.

First experience with ELISA serosurvey for tick-borne borreliosis (Lyme disease) in Czechoslovakia.

Antibodies to Borrelia burgdorferi were searched for in the sera from two groups of hospital patients and one group of healthy agricultural workers. The antibody response was measured by the authors' own modification of the ELISA method employing the antigen prepared from Borrelia recurrentis strain propagated in laboratory mice. Positive antibody titres to Borrelia were demonstrated in 5 out of the 44 patients admitted to the Infectious Diseases Clinic, in 8 out of the 32 patients from the Neurologic Clinic and in 16 out of the 52 healthy agricultural workers living in areas infested with ticks. These findings are interpreted as showing the topicality of the Lyme disease problem in Czechoslovakia.