Intraepidermal nerve-fibre density as a biomarker of the course of neuropathy in patients with Type 2 diabetes mellitus.

AIMS: This paper aims to investigate whether intraepidermal nerve-fibre density (IENFD) may be used as a marker of the course of neuropathy in patients with Type 2 diabetes mellitus. METHODS: Skin biopsies from the distal leg were serially evaluated in a group of 30 patients with Type 2 diabetes mellitus (median age 60 years, 17 men) with a short duration of diabetes (< 3 years) and good glucose control, and in 23 age- and sex-matched controls. The time intervals between biopsies were > 2 years (median 33.8 months). Eighteen patients with Type 2 diabetes mellitus had symptoms or signs of distal symmetrical diabetic polyneuropathy, 12 had no neuropathy. RESULTS: At first skin biopsy, IENFD was normal in all controls and in patients without neuropathy (mean 9.5 and 7.9 fibres/mm, respectively) compared with abnormal IENFD in 77.8% in patients with polyneuropathy (mean 3.4 fibres/mm). The annual rate of intraepidermal nerve-fibre (IENF) loss expressed as a percentage of the first IENFD value in patients with diabetic polyneuropathy was significantly higher [mean (se), 11.95 (3.82)%] compared with controls [1.92 (1.81)%, P < 0.001] and similar to patients without polyneuropathy [12.16 (4.38)%]. The rate of IENF loss did not correlate with degree of glucose control. CONCLUSIONS: The annual rate of IENF loss in patients with Type 2 diabetes mellitus was several times higher than that of healthy participants, irrespective of the presence of signs or symptoms of diabetic polyneuropathy at initial evaluation. The change in IENFD is not linear and should be expressed as a proportion of initial IENFD to serve as a marker of the course of diabetic neuropathy.

Outcomes and their predictors in lumbar spinal stenosis: a 12-year follow-up.

PURPOSE: The aim of this prospective observational cohort study was to evaluate long-term outcomes in patients with mild-to-moderate lumbar spinal stenosis (LSS) and to analyse the predictors of clinical outcomes. METHODS: A group of 53 patients were re-examined after a median period of 139 months. Evaluations were made of subjective clinical outcome, objective clinical outcome and its predictors, any correlation between subjective and objective outcome, and the development of changes in radiological and electrophysiological parameters after 12 years. RESULTS: Satisfactory objective and subjective clinical outcomes were recorded in 54.7 and 43.4% of patients, respectively. No statistically significant correlation between objective and subjective clinical outcome was found (Spearman coefficient = 0.225, p = 0.132). Patients with isolated unsatisfactory subjective outcome exhibited the highest Functional Comorbidity Index of all subgroups. Electrophysiological and radiological findings did not demonstrate statistically significant changes after 12-year follow-up. Multivariate logistic regression confirmed only the lowest transverse diameter of spinal canal ≦13.6 mm as an independent predictor of unsatisfactory clinical outcome (OR = 5.51). CONCLUSIONS: Satisfactory objective and subjective clinical outcomes were disclosed in about half of the patients with mild-to-moderate LSS in a 12-year follow-up. The number of comorbid diseases had an unfavourable effect on subjective evaluation of clinical outcome. The lowest transverse diameter of spinal canal proved to be the only independent predictor of deterioration of clinical status in LSS patients.

Neurological impairment score in lumbar spinal stenosis.

BACKGROUND AND AIM: The Oswestry Disability Index (ODI) is an interview-based instrument generally accepted as a measure of disability in patients with lumbar spinal stenosis (LSS). There is, however, no generally accepted measure for neurological impairment in LSS. We therefore developed a scoring system [neurological impairment score in lumbar spinal stenosis (NIS-LSS)] for the assessment of neurological impairment in the lower limbs of patients with LSS, then performed a validation study to facilitate its implementation in the routine clinical evaluation of patients with LSS. METHODS: The NIS-LSS is based on the combined evaluation of tendon reflexes, tactile and vibratory sensation, pareses, and the ability to walk and run; the total score ranges from 0 (inability to walk) to 33 points (no impairment). A group of 117 patients with LSS and a control group of 63 age- and sex-matched healthy volunteers were assessed with the NIS-LSS to evaluate capacity to discriminate between LSS patients and controls. A correlation with the ODI was performed for assessment of construct validity. RESULTS: The median NIS-LSS was 27 points in LSS patients compared with 33 points in controls. The NIS-LSS discriminated LSS patients from healthy controls to a high degree of significance: the optimum NIS-LSS cut-off value was 32 points with a sensitivity of 85.5% and a specificity of 81.3% (p < 0.001). Overall NIS-LSS correlated significantly with the ODI score (p < 0.001). Vibratory sensation (p = 0.04), presence of paresis (p = 0.01) and especially the ability to walk and run (p < 0.001) were the NIS-LSS elements that correlated most closely with the degree of disability assessed by the ODI. CONCLUSIONS: The NIS-LSS is a simple and valid measure of neurological impairment in the lower limbs of patients with LSS (without comorbidity), discriminating them from healthy controls to a high degree of sensitivity and specificity and correlating closely with the degree of disability. It extends our ability to quantify neurological status and to follow changes arising out of the natural course of the disease or the effects of treatment.

Prediction of long-term clinical outcome in patients with lumbar spinal stenosis.

PURPOSE: The natural course of lumbar spinal stenosis (LSS) fluctuates and is not necessarily progressive. The aim of this study was to explore the predictors of clinical outcome in patients with LSS that might eventually help to optimise the therapeutic choices. METHODS: A group of 56 patients (27 men, 29 women, median age 55; range 31-72 years) with clinically symptomatic mild-to-moderate LSS were re-examined after a median period of 88 months and their clinical outcomes classified as satisfactory (34 patients, 60.7 % with stable or improved clinical status) or unsatisfactory (22 patients, 39.3 % for whom clinical status deteriorated). A wide range of demographical, clinical, imaging and electrophysiological entry parameters were evaluated as possible predictors of clinical outcome. RESULTS: Unlike the demographical, clinical and imaging variables, certain electrophysiological parameters were significantly associated with unsatisfactory outcomes. There was a significantly higher prevalence of pluriradicular involvement detected by EMG in patients with unsatisfactory outcome than those with satisfactory outcome (68.2 vs. 32.3 %; p = 0.035). Patients with unsatisfactory outcome had more frequent bilateral abnormalities of the soleus H-reflex (50.0 vs. 14.7 %; p = 0.015) and lower mean H-reflex amplitude. Multivariate logistic regression proposed two variables as mutually independent predictors of unsatisfactory outcome: EMG signs of pluriradicular involvement (OR = 3.72) and averaged soleus H-reflex amplitude ≤ 2.8 mV (OR = 2.87). CONCLUSIONS: Satisfactory outcomes were disclosed in about 61 % of the patients with mild-to-moderate LSS in a 7-year follow-up. Electrophysiological abnormalities, namely the presence of pluriradicular involvement and abnormalities of the soleus H-reflex, were predictive of deterioration of clinical status in these patients.

Imbalance in T-cell and cytokine profiles in patients with relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) is characterized by autoimmune attack leading to demyelination of the white matter in the central nervous system with devastating clinical consequences. Several immune-mediated destruction mechanisms were previously proposed including different T-cell subsets but complex view on immune system function in patients with MS is missing. In the present study, T-lymphocyte populations and pro-inflammatory as well as suppressive cytokine profiles were evaluated in detail in previously untreated patients with relapsing-remitting MS (RRMS). CD4(+) and CD8(+) naïve, central memory (Tcm), effector memory (Tem), terminal effector memory (Ttem), CD4(+) regulatory T-cells (Treg) and CD8(+) T-suppressor cells (Ts) were analysed using flow cytometry, and levels of ten plasma cytokines were determined using fluorescent bead-based immunoassay. We evaluated two groups of RRMS with minor (n=33) and major (n=25) clinical impairment and compared them with healthy controls (n=40) in order to detect any correlation between severity of MS clinical symptoms and immune disturbances. Significant differences were noted in CD4(+)CD45RA(+)CCR7(+) naïve T-cells, CD4(+)CD45RO(+)CCR7(-) and CD8(+)CD45RO(+)CCR7(-) Tem cells, while no differences were recognized in Tcm, Ttem, Treg and Ts cells in RRMS patients. Nine out of ten studied cytokines were disturbed in plasma samples of patients with RRMS. In conclusion, we demonstrate complex immune dysbalances in untreated MS patients.

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.

Small-fibre involvement in diabetic patients with neuropathic foot pain.

AIMS: To assess small-fibre involvement in diabetic patients with neuropathic pain. METHODS: Peripheral nerve function was assessed in 30 patients with Type 2 diabetes mellitus (T2DM, n = 24) or impaired glucose tolerance (IGT, n = 6), and clinical symptoms of neuropathic pain in the feet, using nerve conduction studies, autonomic tests, thermal quantitative sensory testing (T-QST) and quantification of intra- and subepidermal nerve fibre densities in skin punch biopsies. RESULTS: Clinical signs of isolated small-fibre sensory involvement were present in 13 patients [pure small-fibre neuropathy (pSFN)], seven patients had isolated positive sensory symptoms without neurological deficits (pSFN-). Ten patients had concomitant electrophysiological and/or clinical signs of large-fibre sensory involvement [mixed-fibre neuropathy (MFN)]. Twenty-seven patients (90%) had both reduced skin innervation and abnormalities of the T-QST parameters. Two other patients displayed either abnormal skin innervation or T-QST, and only one patient had normal findings on both tests. The criteria of small-fibre neuropathy (SFN) were met in all 20 patients without large-fibre involvement. Small-fibre involvement was also present in the 10 MFN patients. Both T-QST and skin biopsy parameters revealed significant differences between these clinical subgroups, with increased severity of small-fibre involvement in the MFN group. Autonomic dysfunction was found in 43% of patients and did not correlate with either clinical, T-QST or skin biopsy data. CONCLUSIONS: Although the exact mechanism of neuropathic pain in diabetic patients is not known, pain is almost invariably accompanied by small-fibre dysfunction and pathology irrespective of autonomic or large-fibre involvement.

[Recommendations for early identification of damage to the skeleton by malignant processes, and for early diagnosis of multiple myeloma]. / Doporucení pro casné rozpoznání postizení skeletu maligním procesem a pro casnou diagnostiku mnohocetného myelomu.

The number of newly diagnosed cases of multiple myeloma in the Czech Republic is about 3-4 per 100 000 persons per year. In the higher age groups, the incidence increases. Multiple myeloma is an illness that reacts well to treatment which can result in periods of remission lasting for years. Some of the patients are even able to return to work. A pre-requisite for successful treatment is early diagnosis and this is usually in the hands of first line physicians. This is the reason why the Czech Myeloma Group, in conjunction with neurologists, orthopedicians and radio diagnosticians has issued the following recommendations for first line physicians containing a more detailed description of the symptoms and the diagnostic pitfalls of the disease. This disease reminds a chameleon for the variety of its symptoms. For the sake of clarification, we shall divide multiple myeloma symptoms into five points, each of which is reason enough to warrant an examination to confirm or rule out a malignant cause of health problems (a negative result does not automatically mean exclusion). If any of the recommended examinations results positive, the diagnostic process must be continued, in which case a general practitioner refers the patient to a specialist health centre. Observing these recommendations should minimize the number of cases of late diagnosis. 1. Bone destruction symptoms. - Unexplained backache for more than one month in any part of spine even without nerve root irritability or without pain in other part of skeleton (ribs, hips, or long bones). - Pain at the beginning of myeloma disease is very similar to benigne common discopathy, however the intensity of backache is decreasing within one months in benigne disease. In the case of malignant process the intensity of bone pain is steadily increasing. - Immediate imaging and laboratory investigation are indicated by resting and night pain in spinal column or in any part of skeleton. - Backache with the sign of spinal cord or nerve compression should be sent for immediate X Ray, and focussed CT/MRI followed by acute surgery if needed. - Osteoporosis especially in men and premenopausal women. 2. Features of changed immunity or bone marrow function. Persistent and recurrent infection, typical is normochromic anaemia, with leucopenia and trombocytopenia. 3. Raised erythrocyte sedimentation rate even increase concentration of total plasma protein. 4. Impaired renal function. Increased level of creatinin or proteinuria, nephrotic syndrome with bilateral legs oedema. 5. Hypercalcemia with typical clinical symptoms (polyuria with dehydratation, constipation, nausea, low level conscience, coma). Every one from these points has to be reason for general medical doctor to start battery of tests: -X-ray of bones focused to painful area (mandatory before physiotherapy, local anaesthesia or other empiric therapy). If plain X-ray does not elucidate pain and symptoms are lasting more than one month, please consider all circumstances and results from laboratory investigation. This patient needs referral to the centre with MRI/CT facilities (CT or MRI is necessary investigation in case of nerve root or spine compression). -Investigation of erythrocyte sedimantion rate (high level of sedimentation of erythrocyte can indicate multiple myeloma). -Full blood count. -Basic biochemical investigation serum and urine: serum urea, creatinin, ionts including calcium, total protein, and albumin CRP (high concentration of total protein indicates myeloma, low level of albumin indicates general pathological process, similary increased concentration of fibrinogen, impaired renal function indicates myeloma kidney, however hypercalcemia is typical for highly aggressive myeloma). -Quantitative screening for IgG, IgM and IgA in serum (isolated raised level one of immunoglobulin with decreased level of the others indicates myeloma). -Common electrophoresis of serum is able to detect monoclonal immunoglobulin level at few gramm concentration. If all the laboratory investigation are in normal level the possibility that the current problems are multiple myeloma origine is smaller, but it does not exclude one of rare variant--non secretory myeloma (undifferentiated plasmocyt lost characteristic feature to produce monoclonal immunoglobulin). If any of tests indicate the possibility of myeloma, patient require urgent specialist referral to department with possibility to make diagnosis of malignant myeloma.

Risk factors for critical illness polyneuromyopathy.

Although numerous clinical, laboratory, and pharmacological variables have been reported as significant risk factors for critical illness polyneuromyopathy (CIPM), there is still no consensus on the aetiology of this condition. Objectives of the study were to assess the clinical and electrophysiological incidence and risk factors for CIPM.A cohort of critically ill patients was observed prospectively for a one-month period and the association between neuromuscular involvement and various potential risk factors was evaluated. Sixty one critically ill patients completed the follow-up (30 women, 31 men, median age 59 years).CIPM development was detected clinically in 17 patients (27.9 %) and electrophysiologically in 35 patients (57.4 %). CIPM was significantly associated with the presence and duration of systemic inflammatory response syndrome and the severity of multiple, respiratory, central nervous, and cardiovascular organ failures. The median duration of mechanical ventilation was significantly longer in patients with CIPM than in those without (16 vs 3 days, p<0.001). Independent predictors of CIPM obtainable within the 1(st) week of critical illness were the admission sequential organ failure assessment score (odds ratio [OR], 1.15; 95% confidence interval [CI], 1.02-1.36), the 1(st) week total sequential organ failure assessment scores (OR, 1.14; 95 % CI, 1.06-1.46) and the 1(st) week duration of systemic inflammatory response syndrome (OR, 1.05; 95% CI, 1.01-1.15). They were able to correctly predict the development of CIPM at the end of the 1(st) week in about 80% of critically ill cases.In conclusion, the presence and duration of systemic inflammatory response syndrome and the severity of multiple and several organ failures are associated with increased risk of the development of CIPM.

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.

[Comparison of diagnostic validity of carbohydrate-deficient transferrin and other laboratory markers in chronic ethanol abuse]. / Srovnání diagnostické validity karbohydrát deficientního transferinu a dalsích laboratorních markeru chronického abúzu etanolu.

BACKGROUND: Carbohydrate-deficient transferrin (CDT) has been reported to be the best laboratory marker of the chronic alcohol abuse, but there are conflicting data on its accuracy and sensitivity ranging from 19% to 96% in various studies. The aim of this study was to compare the diagnostic efficiency of CDT with the other markers of alcohol abuse used in clinical practice with respect to possible sex differences. METHODS AND RESULTS: The serum CDT (using the method of anion-exchange chromatography and TIA), mean corpuscular volume (MCV), gamma-glutamyl-transferase (GMT) values and platelet count were evaluated in 50 alcohol-dependent patients admitted to the Center of Detoxification and in the reference group of 85 healthy teetotallers. The cut-off values for %CDT where established in the level of 2.2% and 2.5% for men and women respectively. In men we proved a comparatively high diagnostic efficiency of CDT (AUC 0.94, sensitivity 82.6%, specificity 96.7%) and GMT, MCV seem to be less accurate marker of chronic alcohol abuse. In contrast there was a lower diagnostic validity of CDT in women in comparison with common markers (AUC 0.83, sensitivity 60%, specificity 88%). CONCLUSIONS: The laboratory diagnosis of chronic alcohol consumption can be improved by using a combination of several markers. The specificity and also the cumulative sensitivity of such a battery of laboratory markers can be elevated by CDT evaluation. In a part of patients, CDT can be the only detectable abnormality.

[Diagnostic value of carbohydrate-deficient transferrin, gamma-glutamyltransferase and mean erythrocyte volume as laboratory markers of chronic alcohol abuse]. / Diagnostická výteznost karbohydrát deficitního transferinu, gama-glutamyltransferázy a stredního objemu erytrocytu jako laboratorních markeru chronického abúzu alkoholu.

INTRODUCTION: Our research aimed at finding out values of carbohydrate-deficient transferin (CDT), gamma-glutamyltransferase (GGT) and mean corpuscular volume (MCV) for the purposes of future etiological diagnostics of alcohol neuropathy in thin fibres. METHODS: We examined the serum of 80 control subjects (50 women and 30 men), and the serum of 33 alcoholics (20 men and 13 women) with the daily consumption of more than 60 g alcohol in the course of the last four weeks. CDT was determined with the use of microcolumn separation after iron saturation followed by turbidimetric immunoassay (ChronoAlcoI. D., Sangui Biotech, Inc.) on Cobas-Mira analyser. CDT is expressed as a percentage of the total transferin. Senzitivity, specificity, positive likelihood ration (+LR), ROC and the area under the ROC curve were determined using statistical program MedCalc. RESULTS: The senzitivity, specificity and positive likelihood ratio (+LR) for CDT-%, respectively, were 82.6, 96.7 and 24.8 for men (cut off 2.2%), and 60.0, 88.0 and 5.0 for women (cut off 2.5%). The respective values for GMT were 95.7, 90.0 and 9.6 for men (cut off 0.64 mu kat/l), and 90.0, 80.0 and 4.5 for women (cut off 0.38 mu kat/l); for MCV 82.6, 96.7 and 24.8 for men (cut off 95.0 fL), and 80.0, 100.0 and 20.0 for women (cut off 97.2 fL). The area under the ROC curve for CDT-%, GMT and MCV, respectively, were 0.940, 0.964 and 0.896 for men, and 0.829, 0.917 and 0.906 for women. CONCLUSION: In men, CDT-% and MCV showed the same values of the statistical parameters studied. GGT was more sensitive and less specific. In women, all the parameters studied presented a lesser diagnostic value, except for MCV with 100% specificity and +LR 20.0.

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.

[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.

Conservative treatment versus surgery in spondylotic cervical myelopathy: a prospective randomised study.

A prospective randomised 2-year study was performed to compare the conservative and operative treatment of mild and moderate forms of spondylotic cervical myelopathy (SCM). Forty-eight patients presenting with the clinical syndrome of SCM, with a modified Japanese Orthopaedic Association (mJOA) score of 12 points or more, were randomised into two groups. Group A, treated conservatively, consisted of 27 patients, mean age 55.6 +/- 8.6 years, while group B was treated surgically (21 patients, mean age 52.7 +/- 8.1 years). The clinical outcome was measured by the mJOA score, recovery rate (RR), timed 10 m walk, score of daily activities (recorded by video and evaluated by two observers blinded to the therapy), and by the subjective assessment of the patients at 6, 12, and 24 months of the follow-up. There was, on average, no significant deterioration in mJOA score, recovery ratio, or timed 10 m walk within either group during the 2 years of follow-up. In the surgery group there was a slight decline in the scores for daily activities and subjective evaluation. A comparison of the two groups showed no significant differences in changes over time in mJOA score or quantified gait, but there were significant differences in the score of daily activities recorded by video at 24 months, which was a little lower in the surgical group, and also in RR and subjective evaluation, which were both worse in the surgical group at months 12 and 24. However, at month 6, this last parameter was significantly better in the surgical than in conservative group. Surgical treatment of mild and moderate forms of SCM in the present study design, comprising the patients with no or very slow, insidious progression and a relatively long duration of symptoms, did not show better results than conservative treatment over the 2-year follow-up.

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.

[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.