Coenzyme Q10 deficiency and isolated myopathy.

Three unrelated, sporadic patients with muscle coenzyme Q10 (CoQ10) deficiency presented at 32, 29, and 6 years of age with proximal muscle weakness and elevated serum creatine kinase (CK) and lactate levels, but without myoglobinuria, ataxia, or seizures. Muscle biopsy showed lipid storage myopathy, combined deficiency of respiratory chain complexes I and III, and CoQ10 levels below 50% of normal. Oral high-dose CoQ10 supplementation improved muscle strength dramatically and normalized serum CK.

Mutations in the acid alpha-glucosidase gene (M. Pompe) in a patient with an unusual phenotype.

Glycogenosis type II (Pompe disease) is a lysosomal storage disease caused by deficiency of acid alpha-glucosidase (acid maltase). The disease is autosomal recessive inherited and is clinically and genetically heterogenous. The authors describe a 30-year-old woman affected by late-onset Pompe disease with vascular affection resembling atherosclerotic angiopathy of the elderly. Genetic analysis revealed two novel mutations (Ala237Val and Gly293Arg) in the acid alpha-glucosidase gene in this patient.

Detection of elevated N epsilon-carboxymethyllysine levels in muscular tissue and in serum of patients with fibromyalgia.

OBJECTIVES: To compare levels of the advanced glycation end product (AGE) N(epsilon)-carboxymethyllysine (CML) present in the muscle tissue and in the serum of patients with fibromyalgia (FM) vs. healthy controls. METHODS: The serum levels of CML were measured in 41 patients with FM and 81 healthy controls. The presence of CML, nuclear factor kappa B (NF-kappaB), the AGE receptor (RAGE), collagen types I, II, VI, and CD68-positive monocytes/macrophages in muscle tissue of 14 patients with FM was investigated by immunohistochemistry. RESULTS: Patients with FM showed significantly increased serum levels of CML in comparison to healthy controls. The immunohistochemical investigation revealed a stronger staining for CML and NF-kappaB and more CD68-positive monocytes/macrophages in the muscle of FM patients. The collagens and CML were co-localized, suggesting that the AGE modifications were related to collagen. RAGE was absent in controls but a faint and patchy staining was seen in FM. CONCLUSIONS: In the interstitial connective tissue of fibromyalgic muscles we found a more intensive staining of the AGE CML, activated NF-kappaB, and also higher CML levels in the serum of these patients compared to the controls. RAGE was only present in FM muscle. AGE modification of proteins causes reduced solubility and high resistance to proteolytic digestion of the altered proteins (e.g. AGE-modified collagens). AGEs can stimulate different types of cells by activation of the transcription factor NF-kappaB, mediated by specific receptors of AGEs (e.g. RAGE) on the cell surface. Both mechanisms may contribute to the development, perpetuation, and spreading of pain characteristic in FM patients.

Fibromyalgia-symptom or diagnosis: a definition of the position.

According to the American College of Rheumatology the diagnosis of fibromyalgia is based on criteria for the classification of fibromyalgia consisting entirely of clinical signs and symptoms. For diagnostic reasons autonomic disturbances and mental features have to be considered. The distinction between fibromyalgia (tender points) and myofascial pain syndrome (trigger points) is essential. Internal and neurological disorders as a primary cause of fibromyalgia have to be excluded. The etiology and pathogenesis of fibromyalgia still remain uncertain. The myopathological patterns in fibromyalgia are non-specific: type II fiber atrophy, an increase of lipid droplets, a slight proliferation of mitochondria, and a slightly elevated incidence of ragged red fibers. Initial reports on some allelic abnormalities in the serotonin system seem to highlight the important role of serotonin already presumed earlier. Significantly high levels of substance P in the cerebrospinal fluid of FM patients additionally support the impact of these neurotransmitters on both nociceptive and antinociceptive mechanisms.

The T102C polymorphism of the 5-HT2A-receptor gene in fibromyalgia.

Based on a possible involvement of serotonergic dysfunction in the pathophysiology of fibromyalgia (FM) and on preliminary reports of a possible genetically driven vulnerability for this disorder we investigated the silent T102C polymorphism of the 5-HT2A-receptor gene in 168 FM patients and 115 healthy controls. Our results showed a significantly different genotype distribution in FM patients with a decrease in T/T and an increase in both T/C and C/C genotypes as compared to the control population (Fisher's Exact test, two-sided, P = 0.008). However, the increase in allele-C102 frequency felt short of significance (P = 0.07). Correlation of genotypes to clinical parameters revealed no influences on age of onset, duration of disease or psychopathological symptoms, measured with the Beck Depression Inventory and the symptom checklist SCL-90-R. In contrast to that the pain score, being a self reported information on pain severity, was significantly higher in patients of the T/T genotype (Mann-Whitney U test, P = 0.028). This suggests that the T102-allele might be involved in the complex circuits of nociception. However, the T102C polymorphism is not directly involved in the aetiology of FM but might be in linkage dysequilibrium with the true functional variant, which has to be unravelled.

Relationship of substance P, 5-hydroxyindole acetic acid and tryptophan in serum of fibromyalgia patients.

The serotonergic system has repeatedly been discussed to be involved in the pathophysiology of fibromyalgia (FM), which is a syndrome of widespread pain and sleep disturbance. Elevated levels of substance P (SP), a mediator of nociception, have been described in FM. In this study the possible relationship between SP and serotonin (5-HT) together with its precursor tryptophan (TRP) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) was evaluated in 51 serum samples of fibromyalgia patients. These parameters were compared with clinical data such as pain intensity or sleep quality. A strong negative correlation between SP and 5-HIAA (P = .000) as well as between SP and TRP (P = .009) could be demonstrated. High serum concentrations of 5-HIAA and TRP showed a significant relation to low pain scores (5-HIAA: P = .030; TRP: P = .014). Moreover, 5-HIAA was strongly related to good quality of sleep (P = .000), while SP was related to sleep disturbance (P = .005). These data are valid to support the hypothesis of a systemic involvement of 5-HT and SP in fibromyalgia.

Immunosuppressive treatment of rippling muscles in patients with myasthenia gravis.

Rippling muscle disease is a rare autosomal dominant disorder that may occur sporadically. In this report two patients presenting with rippling muscles followed by myasthenia gravis are described. Our first patient developed rippling muscles about 1 month after infection with Yersinia enterocolitica. Two years later myasthenia gravis appeared. Our second patient had a 2-year history of asthma prior to the onset of rippling muscles which preceded the myasthenic symptoms by 4-8 weeks. Acetylcholine receptor and anti-skeletal muscle antibody titers were positive in both patients. In both patients the rippling phenomena worsened with pyridostigmine treatment but markedly improved after immunosuppression with azathioprine.

A systematic mutation screen of 10 nuclear and 25 mitochondrial candidate genes in 21 patients with cytochrome c oxidase (COX) deficiency shows tRNA(Ser)(UCN) mutations in a subgroup with syndromal encephalopathy.

COX deficiency is believed to be the most common defect in neonates and infants with mitochondrial diseases. To explore the causes of this group of disorders, we examined 25 mitochondrial genes (three COX subunit genes and 22 tRNA genes) and 10 nuclear COX subunit genes for disease associated mutations using PCR-SSCP and direct sequencing of polymorphic SSCP fragments. DNA from one patient with severe COX deficiency and with consanguineous parents was entirely sequenced. The patient population consisted of 21 unrelated index patients with mitochondrial disorders and predominant (n=7) or isolated (n=14) COX deficiency. We detected two distinct tRNA(Ser)(UCN) mutations, which have been recently described in single kindreds, in a subgroup of four patients with COX deficiency, deafness, myoclonic epilepsy, ataxia, and mental retardation. Besides a number of nucleotide variants, a single novel missense mutation, which may contribute to the disease phenotype, was found in the mitochondrial encoded COX 1 gene (G6480A). Mutations in nuclear encoded COX subunit genes were not detected in this study.

Breaking the news in amyotrophic lateral sclerosis.

Telling the diagnosis to patients with amyotrophic lateral sclerosis (ALS) is a daunting task for any neurologist. Obviously, breaking the news in ALS is not a standardizable procedure. However, proven techniques exist to reduce the trauma to the patient and ease the burden on the doctor, thus reducing the risk of burnout and the tendency to 'pull away' from the patient. Such communication skills are of fundamental importance to clinical practice and should be more prominent in medical teaching. The way the patient is told the diagnosis is now recognized to be the first and one of the most delicate steps in palliative care. Information is best offered in a stepwise fashion at the patient's pace with an emphasis on positive aspects, and in the presence of the patient's family. Reviewing available therapeutic options and current research efforts may foster hope for the future, while pointing out that almost all symptoms of ALS can be alleviated by palliative therapy may help to reduce fears. Encouraging patients to ask questions and disclose anxieties is important for their psychological wellbeing. Available options for mechanical ventilation should be reviewed early enough to allow for unhurried decision-making. We believe that the terminal phase of the disease should be discussed at the latest when dyspneic symptoms appear, in order to prevent unwarranted fears of 'choking to death'.

[Myofascial pain syndrome--frequent occurrence and often misdiagnosed]. / Das myofasziale Schmerzsyndrom--häufig vorhanden und häufig verkannt.

Myofascial pain syndrome (MPS) is a very common localized--sometimes also polytopic--painful musculoskeletal condition associated with trigger points, for which, however, diagnostic criteria established in well-designed studies are still lacking. These two facts form the basis for differentiating between MPS and the fibromyalgia syndrome. The difference between trigger points (MPS) and tender points (fibromyalgia) is of central importance--not merely in a linguistic sense. A knowledge of the signs and symptoms typically associated with a trigger point often obviates the need for time-consuming and expensive technical diagnostic measures. The assumption that many cases of unspecific complaints affecting the musculoskeletal system may be ascribed to MPS makes clear the scope for the saving of costs.

Adult human cardiomyocytes coexpress vimentin and Ki67 in heart transplant rejection and in dilated cardiomyopathy.

BACKGROUND: The aim of this study was to investigate whether adult human cardiomyocytes may reexpress vimentin and whether this is linked to cellular activation. METHODS: Myocardial samples of 81 heart transplant recipients (n=183) and patients with dilated cardiomyopathy (n=10) were investigated by immunohistochemistry with the use of the marker molecule vimentin, the muscle-specific protein desmin, and Ki67, a marker for cell activation. RESULTS: Vimentin protein expression in cardiomyocytes was found in 28 samples of transplant recipients and 5 myocardial samples of patients with dilated cardiomyopathy. Coexpression of vimentin and Ki67 was found in 52 of 340 vimentin-positive cardiomyocytes. CONCLUSIONS: We suggest that the vimentin/Ki67 coexpression indicates cell activation processes as the result of different growth stimuli.

Marinesco Sjögren syndrome with rhabdomyolysis. A new subtype of the disease.

Four children from two families with characteristics of Marinesco-Sjögren syndrome (congenital cataract, ataxia) are presented. All children had clinical and neurophysiological signs of a demyelinating polyneuropathy. Three of them developed acute rhabdomyolysis with marked weakness and CK levels of up to 40,000 U/I following a viral infection. In all children CK levels returned to normal within two weeks. Symptoms were recurrent in one of the children and resulted in a severe disability. In two other children recovery of motor function took about a month following the first attack. Metabolic disorders of the muscle were excluded by pathobiochemical examination of a muscle biopsy in one of the children. In conclusion, acute rhabdomyolysis can occur as a neuromuscular complication of Marinesco-Sjögren syndrome.

Morphologic aspects of fibromyalgia.

The most common morphological finding in muscle biopsies in longstanding fibromyalgia is type II fiber atrophy. This can be found in many other conditions such as disuse atrophy, affections of the corticospinal tracts, steroid atrophy, and other different neuromuscular disorders. An increase in lipid droplets and a slight proliferation of mitochondria in type I muscle fibers are correlated with the duration of fibromyalgia. In some cases we could find some ragged red fibers (RRF) which histochemically show a pronounced accumulation of lipids and mitochondria and single fiber defects of cytochrome-c-oxidase. In some fibromyalgia patients with RRF, we could find deletions of the mitochondrial genoma.

[Considerations in patient education in amyotrophic lateral sclerosis (ALS)]. / Gedanken zur Aufklärung bei amyotropher Lateralsklerose (ALS).

Given the relentless progression of amytrophic lateral sclerosis (ALS) and the lack of causative therapy, breaking the news to ALS patients and their families is a daunting task for any physician. Obviously, such a task cannot be standardized. However, it is now recognized to be the first and one of the most sensitive and important steps in palliative care. Information should be offered in a stepwise fashion, in the presence of the patient's family. All questions from the patient should be discussed openly, with emphasis on the positive aspects. Available therapeutic options should be reviewed, pointing out the fact that all symptoms of ALS can be alleviated by palliative therapy. At the onset of dyspneic symptoms, the terminal phase of the disease and the option of mechanical ventilation should be discussed.