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1.
Prilozi ; 32(1): 113-25, 2011.
Article in English | MEDLINE | ID: mdl-21822182

ABSTRACT

Campylobacter jejuni (C. jejuni) infection frequently triggers autoimmune-mediated neuropathies, especially the Guillain-Barre syndrome (GBS). The molecular mimicry between the core oligosaccharides of bacterial lipopolysaccharides (LPSs) and the human gangliosides presumably results in the production of anti-neural cross-reactive antibodies which are likely to be a contributory factor in the induction and pathogenesis of GBS. The aim of our study was to determine the presence of cross-reactive epitopes in C. jejuni LPSs isolated from enteritis patients and to determine their antigen reactivity. For that purpose we collected stool specimens from 21 patients with enteritis and without neurological symptoms. Seven different serotypes of C. jejuni (0:27; 0:6/0:7; 0:38; 0:3; 0:1/0:44; 0:19; 0:37) were detected using the Penner system. Unexpectedly, one serotype from this group was detected as 0:19, a serotype rarely isolated from enteritis patient and in close association with GBS. Binding studies using cholera toxin-B subunit and peanut agglutinin, showed the presence of ganglioside-like epitopes in C. jejuni strains 0:37, 0:19 and 0:27. Reactivity with sera from patient with GBS, with confirmed previous exposure to C. jejuni and with high a titre of anti-ganglioside antibodies, showed that the same three LPSs from C. jejuni serotypes 0:37, 0:19 and 0:27 bear cross-reactive epitopes in their LPSs structures. Our results confirm the results from previous studies that LPSs from certain C. jejuni serotypes bear cross-reactive ganglioside-like epitopes which might be involved in the induction of GBS after C. jejuni infection.


Subject(s)
Campylobacter Infections/immunology , Campylobacter jejuni , Enteritis , Gangliosides/immunology , Guillain-Barre Syndrome/immunology , Adult , Antibodies, Bacterial/immunology , Campylobacter jejuni/genetics , Campylobacter jejuni/immunology , Cross Reactions , Enteritis/immunology , Enteritis/microbiology , Female , Humans , Lipopolysaccharides/immunology , Male , Molecular Mimicry , Serogroup , Serotyping/methods , Statistics as Topic
2.
Eur J Neurol ; 17(7): 893-902, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20402760

ABSTRACT

BACKGROUND: Important progress has been made in our understanding of the autoimmune neuromuscular transmission (NMT) disorders; myasthenia gravis (MG), Lambert-Eaton myasthenic syndrome (LEMS) and neuromyotonia (Isaacs' syndrome). METHODS: To prepare consensus guidelines for the treatment of the autoimmune NMT disorders, references retrieved from MEDLINE, EMBASE and the Cochrane Library were considered and statements prepared and agreed on by disease experts. CONCLUSIONS: Anticholinesterase drugs should be given first in the management of MG, but with some caution in patients with MuSK antibodies (good practice point). Plasma exchange is recommended in severe cases to induce remission and in preparation for surgery (recommendation level B). IvIg and plasma exchange are effective for the treatment of MG exacerbations (recommendation level A). For patients with non-thymomatous MG, thymectomy is recommended as an option to increase the probability of remission or improvement (recommendation level B). Once thymoma is diagnosed, thymectomy is indicated irrespective of MG severity (recommendation level A). Oral corticosteroids are first choice drugs when immunosuppressive drugs are necessary (good practice point). When long-term immunosuppression is necessary, azathioprine is recommended to allow tapering the steroids to the lowest possible dose whilst maintaining azathioprine (recommendation level A). 3,4-Diaminopyridine is recommended as symptomatic treatment and IvIG has a positive short-term effect in LEMS (good practice point). Neuromyotonia patients should be treated with an antiepileptic drug that reduces peripheral nerve hyperexcitability (good practice point). For paraneoplastic LEMS and neuromyotonia optimal treatment of the underlying tumour is essential (good practice point). Immunosuppressive treatment of LEMS and neuromyotonia should be similar to MG (good practice point).


Subject(s)
Autoimmune Diseases/therapy , Clinical Protocols/standards , Neuromuscular Junction Diseases/therapy , Autoimmune Diseases/drug therapy , Autoimmune Diseases/immunology , Evidence-Based Medicine/methods , Evidence-Based Medicine/trends , Humans , Isaacs Syndrome/drug therapy , Isaacs Syndrome/immunology , Isaacs Syndrome/therapy , Lambert-Eaton Myasthenic Syndrome/drug therapy , Lambert-Eaton Myasthenic Syndrome/immunology , Lambert-Eaton Myasthenic Syndrome/therapy , MEDLINE , Meta-Analysis as Topic , Myasthenia Gravis/drug therapy , Myasthenia Gravis/immunology , Myasthenia Gravis/therapy , Neuromuscular Junction Diseases/drug therapy , Neuromuscular Junction Diseases/immunology , Review Literature as Topic
3.
Acta Neurol Scand ; 121(2): 94-8, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19804472

ABSTRACT

OBJECTIVES: To evaluate serum leptin concentration and its relation to metabolic syndrome (MSy) in non-diabetic patients with myotonic dystrophy type 1 (DM1). MATERIALS AND METHODS: This study included 34 DM1 patients, and the same number of healthy subjects matched for age, sex and body mass index (BMI). RESULTS: DM1 patients had increased BMI and insulin resistance, and increased leptin and insulin concentrations, but the other features of MSy such as diabetes, glucose intolerance and hypertension were not detected in DM1 patients. Serum leptin levels were higher in patients with DM1 than in healthy controls (8.5 +/- 6.6 ng/ml vs 3.6 +/- 2.9 ng/ml in men, and 13.9 +/- 10.0 ng/ml vs 10.9 +/- 6.9 ng/ml in women, respectively). In DM1 patients, leptin levels correlated with BMI, fasting insulin and insulin resistance (HOMA) (P < 0.01). CONCLUSIONS: The leptin overproduction correlated with insulin resistance in DM1 patients but the significance of this finding remains unclear.


Subject(s)
Leptin/blood , Metabolic Syndrome/blood , Myotonic Dystrophy/blood , Adult , Blood Glucose , Blood Pressure , Body Mass Index , Cholesterol/blood , Fasting , Female , Glucose Tolerance Test , Humans , Insulin/blood , Insulin Resistance , Male , Metabolic Syndrome/complications , Middle Aged , Myotonic Dystrophy/complications , Sex Characteristics , Triglycerides/blood
4.
Eur J Neurol ; 15(9): 893-908, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18796075

ABSTRACT

Despite high-dose intravenous immunoglobulin (IVIG) is widely used in treatment of a number of immune-mediated neurological diseases, the consensus on its optimal use is insufficient. To define the evidence-based optimal use of IVIG in neurology, the recent papers of high relevance were reviewed and consensus recommendations are given according to EFNS guidance regulations. The efficacy of IVIG has been proven in Guillain-Barré syndrome (level A), chronic inflammatory demyelinating polyradiculoneuropathy (level A), multifocal mononeuropathy (level A), acute exacerbations of myasthenia gravis (MG) and short-term treatment of severe MG (level A recommendation), and some paraneoplastic neuropathies (level B). IVIG is recommended as a second-line treatment in combination with prednisone in dermatomyositis (level B) and treatment option in polymyositis (level C). IVIG should be considered as a second or third-line therapy in relapsing-remitting multiple sclerosis, if conventional immunomodulatory therapies are not tolerated (level B), and in relapses during pregnancy or post-partum period (good clinical practice point). IVIG seems to have a favourable effect also in paraneoplastic neurological diseases (good practice point) [corrected],stiff-person syndrome (level A), some acute-demyelinating diseases and childhood refractory epilepsy (good practice point).


Subject(s)
Immunoglobulins, Intravenous/therapeutic use , Nervous System Diseases/therapy , Autoimmune Diseases of the Nervous System/immunology , Autoimmune Diseases of the Nervous System/therapy , Clinical Trials as Topic , Combined Modality Therapy , Demyelinating Diseases/immunology , Demyelinating Diseases/therapy , Epilepsy/therapy , Evidence-Based Medicine , Humans , Immunoglobulins, Intravenous/administration & dosage , Immunoglobulins, Intravenous/adverse effects , Immunoglobulins, Intravenous/pharmacology , Immunosuppressive Agents/therapeutic use , Paraneoplastic Polyneuropathy/immunology , Paraneoplastic Polyneuropathy/therapy , Paraproteinemias/immunology , Paraproteinemias/therapy , Plasma Exchange
6.
Acta Myol ; 27: 59-62, 2008 Oct.
Article in English | MEDLINE | ID: mdl-19364063

ABSTRACT

Hereditary motor and sensory neuropathy Lom type (HMSNL), also called CMT 4D, a hereditary autosomal recessive neuropathy, caused by mutation in N-Myc downstream regulated gene 1 (NDRG1 gene), was first described in a Bulgarian Gypsy population near Lom and later has been found in Gypsy communities in Italy, Spain, Slovenia and Hungary. We present two siblings with HMSNL, female and male, aged 30 and 26, respectively in a Serbian non-consanguineous family of Gypsy ethnic origin. They had normal developmental milestones. Both had symptoms of lower limb muscle weakness and walking difficulties with frequent falls, which began at the age of seven. At the age of 12, they developed hearing problems and at the age of 15 hand muscle weakness. Neurological examination revealed sensorineural hearing loss, dysarthria, severe distal and mild proximal muscle wasting and weakness, areflexia and impairment of all sensory modalities of distal distribution. Electrophysiological study revealed denervation with severe and early axonal loss. Sensorineural hearing loss was confirmed on electrocochleography and brainstem evoked potentials. Molecular genetic testing confirmed homozygote C564t (R148X) mutation in NDRG1 gene.


Subject(s)
Hereditary Sensory and Motor Neuropathy/genetics , Adult , Cochlear Nerve/physiopathology , Female , Hearing Loss, Sensorineural/diagnosis , Hearing Loss, Sensorineural/genetics , Hearing Loss, Sensorineural/physiopathology , Hereditary Sensory and Motor Neuropathy/blood , Humans , Male , Neurologic Examination , Otoacoustic Emissions, Spontaneous , Roma/genetics , Serbia , Siblings , Vestibular Function Tests
8.
Eur J Neurol ; 13(7): 691-9, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16834699

ABSTRACT

Important progress has been made in our understanding of the cellular and molecular processes underlying the autoimmune neuromuscular transmission (NMT) disorders; myasthenia gravis (MG), Lambert-Eaton myasthenic syndrome (LEMS) and neuromyotonia (peripheral nerve hyperexcitability; Isaacs syndrome). To prepare consensus guidelines for the treatment of the autoimmune NMT disorders. References retrieved from MEDLINE, EMBASE and the Cochrane Library were considered and statements prepared and agreed on by disease experts and a patient representative. The proposed practical treatment guidelines are agreed upon by the Task Force: (i) Anticholinesterase drugs should be the first drug to be given in the management of MG (good practice point). (ii) Plasma exchange is recommended as a short-term treatment in MG, especially in severe cases to induce remission and in preparation for surgery (level B recommendation). (iii) Intravenous immunoglobulin (IvIg) and plasma exchange are equally effective for the treatment of MG exacerbations (level A Recommendation). (iv) For patients with non-thymomatous autoimmune MG, thymectomy (TE) is recommended as an option to increase the probability of remission or improvement (level B recommendation). (v) Once thymoma is diagnosed TE is indicated irrespective of the severity of MG (level A recommendation). (vi) Oral corticosteroids is a first choice drug when immunosuppressive drugs are necessary in MG (good practice point). (vii) In patients where long-term immunosuppression is necessary, azathioprine is recommended together with steroids to allow tapering the steroids to the lowest possible dose whilst maintaining azathioprine (level A recommendation). (viii) 3,4-diaminopyridine is recommended as symptomatic treatment and IvIg has a positive short-term effect in LEMS (good practice point). (ix) All neuromyotonia patients should be treated symptomatically with an anti-epileptic drug that reduces peripheral nerve hyperexcitability (good practice point). (x) Definitive management of paraneoplastic neuromyotonia and LEMS is treatment of the underlying tumour (good practice point). (xi) For immunosuppressive treatment of LEMS and NMT it is reasonable to adopt treatment procedures by analogy with MG (good practice point).


Subject(s)
Autoimmune Diseases of the Nervous System/therapy , Neuromuscular Junction Diseases/therapy , Adrenal Cortex Hormones/therapeutic use , Azathioprine/therapeutic use , Humans , Immunosuppressive Agents/therapeutic use , Lambert-Eaton Myasthenic Syndrome/therapy , MEDLINE/statistics & numerical data , Myasthenia Gravis/therapy , Mycophenolic Acid/analogs & derivatives , Mycophenolic Acid/therapeutic use , Plasma Exchange/methods , Thymectomy/methods
9.
Eur J Neurol ; 13(5): 451-4, 2006 May.
Article in English | MEDLINE | ID: mdl-16722967

ABSTRACT

The purpose of this investigation was to determine survival and mortality in patients with myotonic dystrophy type 1 (DM1) in the Belgrade population within the period from 1983 to 2002. Data of a number of diagnosed DM1 patients with their demographic, clinical and genetic characteristics were gathered from hospital records in all neurologic institutions in Belgrade for the period 1983-2002. Death certificates were reviewed to determine the cause of death. Survival analysis by life table method and Cox proportional hazard model was performed. Within the observed period, in the population of Belgrade, 15 fatal outcomes among 101 patients with DM1 were registered. Average DM1 mortality rate was 0.5/1,000,000 (95% CI 0.3-0.8), and standardized mortality ratio (SMR) was 5.3. A significant inverse correlation was found between age at onset of DM1 and CTG repeats (P=0.023). The cumulative probability of 15-year survival for DM1 patients in Belgrade was 49+/-5% (48+/-2% for males and 50+/-7% for females). Younger age at onset was a significant unfavorable prognostic factor (hazard ratio=4.2; P=0.012).


Subject(s)
Myotonic Dystrophy/therapy , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Myotonic Dystrophy/mortality , Probability , Retrospective Studies , Survival Analysis , Time Factors , Yugoslavia/epidemiology
10.
J Neurol Neurosurg Psychiatry ; 76(8): 1099-102, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16024887

ABSTRACT

OBJECTIVES: To determine if myasthenia gravis (MG) with antibodies to MuSK is a distinct subgroup of seronegative MG. METHODS: We assayed antibodies to muscle specific tyrosine kinase (MuSK) in 55 MG patients who had no antibodies to acetylcholine receptors and looked for the specific phenotype, comparing clinical features of anti-MuSK positive and anti-MuSK negative MG patients. RESULTS: MG with anti-MuSK antibodies was characterised by a striking prevalence of female patients (15 women, two men). Age at onset ranged from 22 to 52 years, with 70.6% of patients presenting at < 40 years of age. The majority of patients (82.4%) had prevalent involvement of facial and bulbar muscles. One third of them did not respond well to anticholinesterase drugs. Steroid immunosuppression was effective in eight patients (44.4%). Nine patients underwent thymectomy; six of these had no thymus pathology, while three had a hyperplastic thymus. At the end of the observation period, six (35.3%) patients were in remission, five (29.4%) improved, four (23.6%) did not change, and two (11.7%) had died. CONCLUSIONS: MG patients with antibodies to MuSK have characteristic clinical features that are different from features of the remaining seronegative MG patients. This emphasises the predictive value of anti-MuSK antibody analysis in seronegative MG patients.


Subject(s)
Autoantibodies/immunology , Myasthenia Gravis/immunology , Receptor Protein-Tyrosine Kinases/immunology , Receptors, Cholinergic/immunology , Adult , Age Distribution , Age of Onset , Electromyography , Female , Humans , Hyperplasia/pathology , Hyperplasia/surgery , Male , Middle Aged , Muscle, Skeletal/immunology , Muscle, Skeletal/physiopathology , Myasthenia Gravis/epidemiology , Myasthenia Gravis/physiopathology , Predictive Value of Tests , Prevalence , Sex Distribution , Thymectomy/statistics & numerical data , Thymus Gland/pathology , Thymus Gland/surgery
11.
Acta Neurol Scand ; 111(4): 247-52, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15740576

ABSTRACT

Cyclosporine A (CsA) treatment was evaluated in 52 patients with severe generalized myasthenia gravis (MG) whose illness was not controlled by anticholinesterase drugs, thymectomy, corticosteroids, and azathioprine. The efficacy of CsA treatment was expressed by mean disability score quotient (MDSQ), which was obtained by comparing mean disability score (MDS) at the beginning of the treatment with the MDS at the end of the follow-up period. For the entire group of patients MDSQ was 53.3%, indicating moderate improvement. Analyzing individual cases, eight patients (15%) did not improve, 17 (33%) showed moderate improvement, 20 (38%) showed remarkable improvement, and seven patients (14%) achieved complete remission. The most common side effects were rise of serum creatinine (seven), hypertension (two), gingival hyperplasia (two), hypertrichosis (six), myalgia (10), and 'flu-like' symptoms (10 patients). The results of this study suggest that CsA is efficacious and safe treatment in severe and resistant forms of MG.


Subject(s)
Cyclosporine/therapeutic use , Immunosuppressive Agents/therapeutic use , Myasthenia Gravis/drug therapy , Adult , Cyclosporine/adverse effects , Disabled Persons , Female , Humans , Immunosuppressive Agents/adverse effects , Male , Middle Aged , Myasthenia Gravis/pathology , Severity of Illness Index , Treatment Outcome
12.
Acta Neurol Scand ; 111(4): 274-7, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15740580

ABSTRACT

OBJECTIVES: Analysis of the CTG-repeat number and three biallelic markers, Alu(+/-), HinfI(+/-), and TaqI(+/-), in the DMPK gene in healthy and myotonic dystrophy type 1 (DM1) Serbian individuals. Also, the consideration of haplotypes in the light of the proposed models of CTG-repeat evolution and origin of the DM1 mutation. MATERIALS AND METHODS: Markers were analyzed by PCR and haplotypes were obtained on 203 unrelated normal chromosomes and 24 unrelated DM1 chromosomes. RESULTS: A strong linkage disequilibrium was detected between the three biallelic markers alone (P <0.0001) and between distinct CTG-repeat size classes and reconstructed haplotypes. Greater than 98% of normal chromosomes contain (+++) and (- - -) haplotypes. The (+++) haplotype is the most common, while the (CTG)(9-17) are the most frequent alleles. We found a complete association of (+++) haplotype with (CTG)(> or =18) and mutated alleles. CONCLUSIONS: (CTG)(9-17)/(+++) haplotype is the ancestral haplotype and DM1 mutation occurred on (CTG)(18-35)/+++ chromosome.


Subject(s)
Myotonic Dystrophy/genetics , Protein Serine-Threonine Kinases/genetics , Case-Control Studies , Female , Genetic Markers , Haplotypes , Humans , Male , Myotonin-Protein Kinase , Pedigree , Trinucleotide Repeats , Yugoslavia
16.
Acta Neurol Scand ; 105(1): 55-8, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11903110

ABSTRACT

OBJECTIVES: Myotonic dystrophy type 1 (DM1) is caused by large expansions of cytosine-thymine-guanine (CTG)-repeats in myotonic dystrophy protein kinase (DMPK)-gene. This gene is highly polymorphic in healthy individuals. It has been proposed that expanded alleles originated from the group of large sized normal alleles. If this is correct, one should expect a positive correlation between the frequency of large sized normal alleles and a prevalence of this disorder in a population. In this paper we determined the distribution of alleles of DMPK gene in healthy Yugoslav population. MATERIAL AND METHODS: A sample of 235 healthy individuals of Yugoslav origin have been genotyped for the alleles of DMPK locus. RESULTS: We found 22 different alleles, ranging in size from 5 to 29 repeats. Among 470 chromosomes studied, 41 chromosomes had more than 18 repeats (8.72%). CONCLUSIONS: Relatively high frequency of large sized normal alleles found in our population, suggest that prevalence of DM1 in Yugoslavia should not be different from the prevalence in other European populations.


Subject(s)
Cytosine Nucleotides/genetics , Gene Frequency/genetics , Guanine Nucleotides/genetics , Myotonic Dystrophy/genetics , Polymorphism, Genetic/genetics , Protein Serine-Threonine Kinases/genetics , Thymine Nucleotides/genetics , Trinucleotide Repeats/genetics , Genotype , Humans , Myotonin-Protein Kinase , Reference Values , White People/genetics , Yugoslavia
17.
Acta Haematol ; 106(3): 130-2, 2001.
Article in English | MEDLINE | ID: mdl-11713380

ABSTRACT

Monocytoid B cell lymphoma (MBCL) is an immunologically and morphologically well-defined low-grade lymphoma with a predilection for lymph nodes of the parotid region. We describe an association of MBCL with anti-myelin-associated glycoprotein (MAG) polyneuropathy in a 53-year-old male. The diagnosis of stage IV MBCL with nodular bone marrow infiltration, Sjögren's syndrome and sensorimotor polyneuropathy was made in October 1996. Serum immunoelectrophoresis demonstrated IgMkappa paraprotein. This was then cross-reacted with epitopes of MAG and sulphated glucuronyl paragloboside (SGPG) on myelin sheaths, and detected by thin layer chromatography and Western blot. Direct immunofluorescence of a sural nerve biopsy showed loss of myelin fibres, segmental demyelinization and IgM deposits on the myelin sheaths. The cerebrospinal fluid was normal. After six cycles of chemotherapy (ChlVPP protocol), all the patient's haematological parameters normalized accompanied by an improvement in neurological signs. The improvement of the polyneuropathy after chemotherapy indicates that the autoimmune anti-MAG and anti-SGPG antibodies resulted from the neoplastic lymphoid proliferation.


Subject(s)
Antibodies, Neoplasm/immunology , Antigens, Neoplasm/immunology , Globosides/immunology , Lymphoma, B-Cell/immunology , Lymphoma, Non-Hodgkin/immunology , Myelin-Associated Glycoprotein/immunology , Neoplasm Proteins/immunology , Paraproteins/immunology , Autoantibodies/immunology , Autoimmune Diseases/complications , Humans , Immunoglobulin M/immunology , Immunoglobulin kappa-Chains/immunology , Lymph Nodes/pathology , Lymphoma, B-Cell/complications , Lymphoma, B-Cell/pathology , Lymphoma, Non-Hodgkin/complications , Lymphoma, Non-Hodgkin/pathology , Male , Middle Aged , Parotitis/etiology , Purpura/etiology , Sensation Disorders/etiology , Sjogren's Syndrome/complications , Spleen/pathology
18.
Psychiatr Genet ; 11(4): 201-5, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11807410

ABSTRACT

A number of human hereditary neuromuscular and neurodegenerative disorders are caused by the expansion of trinucleotide repeats within certain genes. The molecular mechanisms that underlie these expansions are not yet known. We have analyzed six trinucleotide repeat-containing loci [spinocerebellar ataxias (SCA1, SCA3, SCA8), dentatorubral-pallidoluysian atrophy (DRPLA), Huntington chorea (HD) and fragile X syndrome (FRAXA)] in myotonic dystrophy type 1 (DM1) patients (n = 52). As controls, we analyzed two groups of subjects: healthy control subjects (n =133), and a group of patients with non-triplet neuromuscular diseases (n = 68) caused by point mutations, deletions or duplications (spinal muscular atrophy, Charcot-Marie-Tooth disease, type 1A, hereditary neuropathy with liability to pressure palsies, and Duchenne and Becker muscular dystrophy). Allele frequency distributions for all tested loci were similar in these three groups with the exception of the SCA1 locus. In DM1 patients, the SCA1 allele with 31 CAG repeats account for 40.4% of all chromosomes tested, which is significantly higher than in two other groups (11.3% in healthy controls and 6.6% in the group of non-triplet diseased patients; P < 0.001, Fisher's exact test). This is consistent with our previous findings in HD patients. The absence of this association in non-triplet diseases as well as in healthy controls could indicate a possible role of this SCA1 allele with 31 repeats in triplet diseases. Here we discuss a possible role of the SCA1 region in pathological trinucleotide repeat expansions.


Subject(s)
Nerve Tissue Proteins/genetics , Nuclear Proteins/genetics , Spinocerebellar Ataxias/genetics , Trinucleotide Repeats , Alleles , Ataxin-1 , Ataxins , Base Sequence , DNA/blood , DNA/genetics , DNA Primers , Female , Gene Frequency , Humans , Male , Reference Values
19.
Eur J Neurol ; 8(6): 689-92, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11784354

ABSTRACT

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder most commonly caused by a 1.5-Mb deletion in chromosome 17p11.2 which contains the peripheral myelin protein-22 (PMP22) gene. Mutations resulting in functional loss of one PMP22 gene copy are less frequent. We present a 51-year-old patient with a l.5-Mb deletion in chromosome 17p11.2 who exhibited signs of peripheral as well as central nervous system lesions. He gave a history of recurrent episodes of limb numbness and weakness with spontaneous but incomplete recovery since age 20. His father and two brothers had similar symptoms. Neurological examination revealed signs of multiple mononeuropathy associated with frontal lobe, corticospinal tract and cerebellar dysfunction, as well as signs of initial cognitive impairment. Electrophysiological investigations showed a demyelinating peripheral nerve disease with multiple conduction blocks and conduction disturbances in both optic nerves. Magnetic resonance imaging of the brain revealed multiple subcortical and periventricular foci of myelin lesions. The association of central and peripheral nervous system lesions in this patient indicates a possible role of PMP22 not only in peripheral but also in central nervous system myelin structure.


Subject(s)
Brain/pathology , Myelin Sheath/pathology , Chromosomes, Human, Pair 17 , Gene Deletion , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Myelin Proteins/genetics
20.
Srp Arh Celok Lek ; 128(7-8): 247-52, 2000.
Article in Serbian | MEDLINE | ID: mdl-11089431

ABSTRACT

Myasthenia gravis (MG) is an antigen-specific autoimmune disease in which antibodies directed against nicotinic acetylcholine receptors of the postsynaptic muscle membrane (nAChR) impair neuromuscular transmission. MG is clinically characterized by abnormal muscle fatigue and weakness. The initial symptoms and signs are often unrecognized. Therefore, we analyzed the diagnostic errors and duration of diagnostic delay in patients affected with MG (n = 444) in a ten-year period (January 1, 1983-December 31, 1992) in Yugoslavia. The initial diagnosis was correct in 44.4% of patients and erroneous in 38.4%; 17.2% of patients were admitted without an initial diagnosis. The average duration of diagnostic delay was 11 months. We present the differential diagnostic difficulties in MG and discuss the principles of diagnostic strategy which may reduce the risk of diagnostic errors in MG.


Subject(s)
Myasthenia Gravis/diagnosis , Adult , Aged , Diagnosis, Differential , Diagnostic Errors , Female , Humans , Male , Middle Aged
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