[Schnitzler syndrome: case report, the experience with glucocorticoid and anakinra (Kineret) therapies and monitoring of systemic cytokine response]. / Schnitzler-syndrom: popis prípadu, zkusenosti s lécbou glukokortikoidy a preparátem anakinra (Kineret) a sledování cytokinové odpovedi organizmu.

Schnitzler syndrome is a rare idiopathic disease characterized by chronic urtica, presence of monoclonal IgM immunoglobuline and further, less common symptoms. This case report describes another case of this disease affecting a male adult born in 1963. The first symptoms, eruptions of non-pruritic urticarial rash, appeared in this patient at the age of 43. In addition, bone pains (mainly tibias) and joint pains (mainly knees) were present. Later on however, severe attacks of fever, chills and shaking together with bone and joint pains were added to during which new urticarial eruptions appeared. Primarily, the man was followed up without any substantial therapeutic results at a department of dermatovenerology, subsequently, due to a finding of monoclonal IgM kappa immunoglobulin (serum concentration 1.9 g/l) he was referred to our department for the reason of gammopathy being a differential diagnosis. On a CT scan hyperostosis in claviculae and pelvic bones was identified. Also on the CT, an increase in cortical thickness was described in the long bones of the lower extremities, where areas of technetium pyrophosphate accumulation were identified on a bone scintigraphy. These areas were found in the chest and sacral regions as well. From the blood exams, the proinflammatory status of the organism was apparent (CRP 35.9 mg/l, erythrocyte sedimentation rate 92 mm/h, leukocytes 12.4 x 10(9)/l). After excluding other differential diagnoses, the patient was diagnosed with Schnitzler syndrome. As regards therapy, we made initial use of the effect of corticoids which abated the symptoms, however, these were causing serious adverse reactions in the form of iatrogenous Cushing's syndrome. The therapy took a turn only after biologic therapy with anakinra (interleukin-1 receptor antagonist) had started, which minimized the Schnitzler symptoms with very good drug tolerance. In the work we measured serum levels of interleukins for disease activity monitoring. The most sensitive were interleukins IL-6 and especially IL-18 the levels of which were the highest at the time of clinical exacerbation of the disease, whereas the levels of IL-1beta and TNF-alpha (tumour necrosis factor) were during all measurements below the limit of detection. Concerning the growing numbers of the reports on successful biological therapy with anakinra and our positive experience, we propose that the therapeutic response to anakinra should be included within the diagnostic criteria of Schnitzler syndrome, which is significant above all in differential diagnosis thereof.

An objective evaluation of contraction power of neo-phallus reconstructed with free re-innervated LD in female-to-male transsexuals.

AIMS: Objective evaluation of contraction power of the neo-phallus reconstructed with a novel technique in female-to-male transsexuals. PATIENTS AND METHODS: From December 2001 to September 2005, 22 patients with gender identity disorder underwent neo-phalloplasty with the re-innervated latissimus dorsi free flap. All the patients were subjected to an early rehabilitation protocol of the transferred muscle; the beginning time of neo-phallus voluntary contraction was recorded in 18 patients. 14 patients, who came for examinations, were objectively evaluated for the strength of transplanted muscle contraction in neo-phallus by electromyography and measurement of the maximum weight lifted. RESULTS: 18 patients were able to voluntarily contract the neo-phallus after an average period of 4.11 months. In 14 of them, the average weight lifted was 1129 g. After electromyography, the mean number of positive peaks in the 100 ms period was 31.5; the mean amplitude from 10 highest positive peaks, measured peak-to-peak, was 0.99 mV. DISCUSSION AND CONCLUSION: The advantage of this technique is non-requirement of the prosthesis for sexual activity due to the development of strong voluntary contraction of the neo-phallus. Our findings document objectively the strength of voluntary contraction of the neo-phallus as a consequence of re-innervation of the transferred muscle. Furthermore, data represent useful tool for clinical assessment and comparison.

Mitoxantrone therapy in rapidly worsening multiple sclerosis.

BACKGROUND: This study evaluates mitoxantrone (MX) therapy in patients with relapsing remitting and secondary progressive multiple sclerosis (MS). OBJECTIVES: Evaluation of the disability progression and side effects of MX. METHODS: There were studied 33 patients (10 males, 23 females), average age 48.5+/-9.9 SD) with relapsing remitting and secondary progressive MS. The disability was evaluated using Expanded Disability Status Scale (EDSS). Time period from the onset to secondary progressive course of the disease was 9.3 years. Patients, whose disability progression increased by one or more EDSS point per one year, and not responding to other therapy, were treated with mitoxantrone. Patients were treated once monthly with intravenous administration of mitoxantrone 12 mg/m2, not exceeding the maximum cumulative dose of 14 mg/m2 and Solu-Medrol 1000 mg. Six pulses were done in each patient. EDSS score was measured at the beginning of the treatment and after twelwe month. Disability progression was evaluated. Nonparametric Wilcoxon matched pair test was used for statistical analysis. (Tab. 1, Fig. 3, Ref: 5.)

A mutation in the X-linked Emery-Dreifuss muscular dystrophy gene in a patient affected with conduction cardiomyopathy.

A screening for mutation in the X-linked Emery-Dreifuss muscular dystrophy (X-EMD) gene was performed among patients affected with severe heart rhythm defects and/or dilated cardiomyopathy. Patients were selected from the database of the Department of Cardiology of the University Hospital Brno. One patient presented a mutation in the X-EMD gene and no emerin in his skeletal muscle. The patient had a severe cardiac disease but a very mild muscle disorder that had not been diagnosed until the mutations was found. This case shows that mutations in X-EMD gene, as it was shown for autosomal-dominant EMD, can cause a predominant cardiac phenotype.

Median nerve mononeuropathy in spondylotic cervical myelopathy: double crush syndrome?

We studied the association between spondylotic cervical myelopathy (SCM) and median nerve mononeuropathy (MNM) and examined the validity of the double-crush hypothesis. Sixty consecutive patients with clinically overt spondylotic cervical myelopathy were examined by means of nerve conduction studies, electromyography, and median nerve somatosensory evoked potentials; the frequency of the electrophysiological signs of focal MNM at the wrist was compared with that of a control group comprising 100 sex- and age-matched patients. Electrophysiological signs of MNM were found in 20 myelopathic patients (33%) in comparison with an 11% prevalence in the control group (P<0.05). The signs of motor anterior horn cell lesion at the C8-Th1 level and concomitant motor axonal MNM ipsilaterally were found in three hands, while the signs of sensory axonal loss at C6-7 segments due to ganglionic or postganglionic sensory lesion outside the wrist and concomitant sensory axonal MNM were present in one hand. While demonstrating a statistically significant association between SCM and MNM, we found no evidence of an etiological relationship between these two conditions. Electrophysiological signs of MNM fail anatomical (segmental level and side) and pathophysiological (axonal type of lesion) requirements of the double-crush hypothesis in most of patients with concomitant SCM and MNM.

The value of somatosensory- and motor-evoked potentials in predicting and monitoring the effect of therapy in spondylotic cervical myelopathy. Prospective randomized study.

STUDY DESIGN: A 2-year follow-up prospective randomized electrophysiologic and clinical study of patients with spondylotic cervical myelopathy. OBJECTIVE: To assess the value of somatosensory- and motor-evoked potentials in the evaluation and prediction of the effect of therapy. SUMMARY OF BACKGROUND DATA: Previous studies have yielded conflicting data concerning the correlation between the changes in evoked potential parameters and the clinical postsurgical outcome in spondylotic cervical myelopathy. METHODS: Sixty-one patients with magnetic resonance images suggesting spondylotic cervical cord compression and clinical signs of cervical myelopathy were divided into two groups according to the degree of clinical cervical cord involvement. The 49 patients with mild and moderate spondylotic cervical myelopathy were randomized into groups that underwent either surgical or conservative therapy. Patients were evaluated clinically and by the means of somatosensory- and motor-evoked potentials. RESULTS: The clinical and evoked potential changes showed good correlation on the group level, but poor correlation intraindividually. There were no significant evoked potential and clinical group changes after 6 months and 2 years in the mild myelopathy group treated either surgically and conservatively, whereas patients with severe myelopathy displayed significant improvement in clinical and evoked potential parameters after surgery. In a subgroup of patients, the isolated segmental medullar N13 abnormality could potentially predict favorable postsurgical clinical outcome. CONCLUSIONS: Longitudinal evoked potentials showed limited use for evaluating the results of therapy in an individual patient. They could be useful in the group assessment of therapy results and in labeling a subgroup of patients with potentially favorable postsurgical outcome.

[Compressive ischemic neuropathies of the upper extremities and work]. / Kompresivne ischemické neuropatie na horních koncetinách a práce.

The objective of the presented study was to motile that cumulative trauma disorders of the upper extremities in recent years leads to arising morbidity and applications for compensation for occupational diseases. This rise is probably not associated with an increase of this disorder but a different awareness of workers and doctors as regards the possible adverse effect of forceful and frequently repeated movements of the upper extremities on their function, extended diagnostics and notification. It is important to master the diagnosis of these diseases and interpretation of auxiliary examinations to prevent inadequate payment of damages to the affected subjects and on the other hand to prevent breakdown or in adequate function of the financial provisions in this area. A number of syndromes of the mentioned conditions has very few objective symptoms and abnormal results of auxiliary examinations. The diagnosis of stenotic syndromes has a compared with other disorders great support in electrophysiological techniques, their high sensitivity and specificity (1, 15). The authors discuss therefore their problems and suggest electrophysiological criteria of medium grade affections in the carpal tunnel syndrome which is the condition for compensation for occupational disease and which so far was defined only roughly in this country.

[Adverse effects of administration of intravenous human immunoglobulins]. / Nezádoucí úcinky podání intravenózního lidského imunoglobulinu.

Treatment with intravenous human immunoglobulin (IVIG) has become a routine therapeutic method in immunodeficiency states and autoimmune diseases. Although it is a relatively safe therapeutic method it may have serious undesirable effects. Knowledge of these undesirable effects is the prerequisite for coping with them and in some instances it is possible to prevent them. Undesirable effects of IVIG administration can be divided into six groups: 1. Generalized reaction, in particular fever, shiver, nausea, vomiting, tachycardia, dyspnoea, changes of blood pressure are recorded in less than 5% patients, usually during infusion and depend on the rate of administration. 2. Hypersensitivity and anaphylactic reactions may be also severe to fatal and are usually the manifestation of the action of antibodies against IgA; they may be anticipated in particular in patients with deficiency of class A immunoglobulins and in patients with autoimmune diseases. 3. Haematological: rare and usually clinically irrelevant haemolytic anaemia. 4. Neurological: frequent and minor headache, rarely relapsing aseptic meningitis syndrome. 5. Nephrological: renal failure which developed by the mechanism of osmotic nephrosis, relatively very rare, affecting almost exclusively patients with nephropathy present before administration of IVIG. 6. Thrombotic complications manifested by cerebral ischaemia. They are however extremely rare and their relationship to IVIG administration is controversial. At present we can rule out transmission of viral infection by IVIG preparations with the exception of transmission of the hepatitis C virus.

[Postpoliomyelitis syndrome and progressive postpoliomyelitis muscular atrophy]. / Postpoliomyelitický syndrom a progresivní postpoliomyelitická svalová atrofie.

New complaints of patients after poliomyelitis following after decades of a stabilized condition are described by the term postpoliomyelitic syndrome (PPS). They affect at least half the patients after poliomyelitis. The best defined picture from a broad spectrum of new complaints is so-called progressive postpoliomyelitic atrophy (PPMA). The authors review contemporary knowledge of the etiopathogenesis of PPS and PPMA and their possible therapy.

[Muscular dystrophies detected by immunophenotyping and genotype analysis (mRNA and DNA)]. / Svalové dystrofie detekované imunofenotypizací a analýzou genotypu (m-RNA a DNA).

Complex diagnosis of muscular dystrophies including clinical, bioptical and molecular genetic approaches has been provided in a limited extent in this country. Our group of neurologists, pathologists and geneticists has examined approximately 240 patients suspected of having muscular dystrophies, mostly coming from Southern and Northern Moravia. The patients were sent to the examination most often from departments of neurology and clinical genetics, and less frequently from departments of internal medicine. According to the final diagnosis, the patients were divided into groups: with dystrophinopathies and carriers of dystrophinopathies (DMD/BMD), merosin deficient form of congenital muscular dystrophy, and Emery-Dreifuss muscular dystrophy including the carriers of this disease. Some relatives of patients with dystrophinopathies were also examined using the methods of segregation analysis. High proportion of the DMD/BMD patients can be detected by the methods of molecular genetics. Analysis of mRNA using RT PCR and PTT enables the detection of deletions, duplications, and point mutations in dystrophin gene and encompasses a larger diagnostic scope in comparison with examinations of DNA level by the multiplex PCR method from the peripheral blood which enables only deletion detections. Immunophenotyping of the dystrophin protein plays an important role especially using antibodies against carboxyterminal (DYS2) and rod domain (DYS1) of dystrophin. Deficient sarcolemmal expression of DYS2 and DYS1 reveals unambiguously a pathological dystrophin. On the other hand, less pronounced deficiencies in dystrophin expression in BMD patients and DMD/BMD carriers may not always be detected in muscle biopsies. In this case, it is necessary to supplement the examination by Western blotting and genotype analysis. The examination of patients with clinically diagnosed muscular dystrophy should start with a muscle biopsy which enables the estimation of presence and degree of structural changes. Application of antibodies against the components of DGC and emerin may reveal a deficiency in expression of these proteins. Immunohistochemical examination completed by Western blotting leads to the subsequent molecular genetic analysis of DNA or mRNA. Secondary deficiencies in expression of other DGC proteins are often revealed in muscle biopsies of dystrophinopathies and this fact must be taken into account in the evaluation of immunohistochemical findings. There is a possibility of replacement of invasive muscle biopsy by skin biopsy or buccal mucosal smears in cases of merosin and emerin deficiencies. Commercially available antibodies against merosin, emerin, calpain and sarcoglycans enable extensive identification and detailed classification of muscular dystrophies. Screening of the patients based on the application of methods described and discussed in this report is the task of the forthcoming period.

[Surgical treatment of cervical spondylotic myelopathy in the Czech and Slovak Republic in 1994]. / Stave operacní terapie spondylogenní cervikální myelopatie v Ceské a Slovenské republice v roce 1994.

The authors investigated the state of surgery on account of cervical spondylosis and in particular spondylogenic cervical myelopathy in the Czech and Slovak Republic in 1994. They assessed the number of operated patients, surgical methods, indication criteria and the diagnostic strategy of different departments. The total number of patients operated on account of cervical spondylosis in 1994 was 347, incl. 113 on account of cervical spondylogenic myelopathy. As to surgical techniques in the majority the anterior approach was selected (Smith-Robinson's method). Laminectomy was performed in 14 and laminoplasty in 22 cases. The number of operated patients is, as compared with the frequency of similar operations in the United States, six times lower. As all departments where enquiries were made operate every cervical compression regardless of the degree of functional deficiency, this may reflect inadequate diagnosis of the disease.

Matrix metalloproteinase-9 and matrix metalloproteinase-2 as biomarkers of various courses in multiple sclerosis.

BACKGROUND: Matrix metalloproteinases are notable contributors to neuroinflammation and blood-brain barrier disruption in multiple sclerosis (MS). OBJECTIVE: The goal of this study was to determine the serum levels of matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-2 (MMP-2), and their tissue inhibitors (TIMP-1) and (TIMP-2), and to investigate their possible relations to type, disability, and severity of MS. MATERIALS AND METHODS: Eighty-seven patients with definite MS according to the McDonald criteria and 50 healthy controls were enrolled in the study. Their clinical status was evaluated with the Expanded Disability Status Scale. Serum levels were analyzed by enzyme-linked immunoassay. RESULTS: A significant elevation in MMP-9 serum levels and in the MMP-9/TIMP-1 ratio was found in the whole MS group (P<0.001), in the relapsing-remitting MS (RRMS) (P<0.001), and secondary-progressive MS (SPMS) (P<0.001) groups when compared with the controls. A significant elevation in MMP-2 serum levels and in the MMP-2/TIMP-2 ratio was observed in the primary progressive (P<0.001) and the SPMS (P<0.002) groups when compared with the RRMS group, and this increase was also associated with the disability (P<0.001) and severity (P<0.05) of the disease. CONCLUSION: We confirmed that metalloproteinases are useful biological markers in MS, providing information about the clinical type, disability, and severity of the disease.

Predictive factors for mild forms of spondylotic cervical myelopathy treated conservatively or surgically.

A prospective 3-year randomized study comparing conservative and surgical treatment of spondylotic cervical myelopathy to establish predictive factors for outcome after conservative treatment and surgery. The clinical, electrophysiological and imaging parameters were examined to reveal how they characterized the clinical outcome. Statistically, pair-wise and multiple comparisons of different were used with the independent t-test and on one-way anova models followed by Tukey multiple-range tests. The patients with a good outcome in the conservatively treated group were of older age before treatment, had normal central motor conduction time (CMCT), and possessed a larger transverse area of the spinal cord. The patients with a good outcome in the surgically treated group had a more serious clinical picture (expressed in mJOA score and slower walk). Patients should rather be treated conservatively if they a spinal transverse area larger than 70 mm2, are of older age, and have normal CMCT. Surgery is more suitable for patients with clinically worse status and a lesser transverse area of spinal cord.

Predictive factors for spondylotic cervical myelopathy treated conservatively or surgically.

A prospective 3-year randomized study comparing conservative and surgical treatment of spondylotic cervical myelopathy to establish predictive factors for outcome after conservative treatment and surgery. The clinical, electrophysiological and imaging parameters were examined to reveal how they characterized the clinical outcome. The patients with a good outcome in the conservatively treated group were of older age before treatment, had normal central motor conduction time (CMCT), and possessed a larger transverse area of the spinal cord. The patients with a good outcome in the surgically treated group had a more serious clinical picture (expressed in mJOA score and slower walk). Patients should rather be treated conservatively if they have a spinal transverse area larger than 70 mm2, are of older age and have normal CMCT. Surgery is more suitable for patients with clinically worse status and a lesser transverse area of spinal cord.

[Transcranial and spinal stimulation of motor pathways using conventional stimulator]. / Transkraniální a spinální stimulace motorické dráhy konvencním stimulátorem.

In a group of 31 subjects with a normal locomotor system in the area of the upper extremities transcutaneous cortical and spinal stimulation was administered using a conventional stimulator with an electromyographic tracing on the contralateral tenar and a common investigation of the motor conduction of the median nerve. The mean latency on stimulation on the calva was 20.0 +/- SD 0.9 ms, the mean amplitude 3.8 +/- SD 1.6 mV. The conduction time between cortex and the cervical spinal area was on average 4.8 +/- SD 0.5 ms, between cortex and wrist 16.26 +/- SD 0.8 ms, the mean latency on spinal stimulation 15.2 +/- SD 0.9 ms. The authors found a statistically significant relationship between the latencies from the calva, and spinal stimulation, with the height of the subject and with the length of the upper extremity, while there was no relationship between the conduction time in the central portion of the motor pathway and these anthropometric parameters. The authors evaluate the risk and tolerance of transcranial stimulation in man.

[Somatosensory evoked potentials in the diagnosis of multiple sclerosis]. / Somatosenzitivní evokované potenciály v diagnostice sclerosis multiplex.

The authors examined SEP in a group of 54 patients with the clinical diagnosis of SM. The sensitivity of the test in SEP of the median nerve was 68%, in SEP of the tibial nerve 78%. Concurrent use of both techniques revealed an abnormality in 83%. Subclinical abnormalities were present in 28% (median nerve) and 24% resp. (tibial nerve) of the patients. In case of a clinical disturbance of sensitivity the SEP finding was normal in 10% of the patients. A typical abnormality in SM was the absence of spinal responses and prolongation of the central conduction time. In 41% of the patients with an abnormal finding the abnormality was unilateral. The authors discuss possibilities of topical diagnosis of sensitive lesions by means of SEP.

Multimodal sensory and motor evoked potentials in a two-year follow-up study of MS patients with relapsing course.

Serial recording of multimodal sensory (pattern reversal visual, brainstem auditory, median and tibial somatosensory) and motor evoked potentials during a 2-year period was performed on a group of 25 patients with relapsing multiple sclerosis. A new, 10-degree evoked potentials abnormality scale was introduced. In contrast to the insignificant common trend of both the mean individual EP latency parameters and the mean expanded disability status scale and evoked potentials abnormality scale to deteriorate the changes in both expanded disability status scale (p less than 0.05) and evoked potentials abnormality scale (p less than 0.01) were significant using a 1-point criterion for change and non-parametric testing. Changes in both scales differed in about 50% of patients; contrary to bidirectional changes in the clinical scale, no improvement in the evoked potential scale was found. The introduction of an evoked potentials abnormality scale based on separate cut-off step-like criteria may increase the robustness of evoked potential changes due to the activity of the disease in longitudinal studies.

Site of motor pathway excitation during cervical spinal stimulation.

In a set of 25 normal subjects the probable site of activation of the motor pathway was looked for using transcutaneous cervical spinal stimulation. The motor conduction time in the fastest fibres between the "spinal cord" and the wrist reached 10.79 (SD 1.17) ms when using this technique and this value was compared to the same parameter obtained with other methods: F wave mean conduction time in the established distance was 11.0 (SD 0.96) ms; the conversion of sensory to motor conduction showed 11.0 (SD 1.1) ms and H wave 10.97 (SD 1.03) ms. The conduction time through the fastest motor fibres with the spinal stimulation corresponds to the activation of the alpha-motoneuron axons near their bodies. When interpreting the results of the cortical and spinal stimulation, it is necessary to take this fact into account.