Cu,Zn SOD in German families with ALS.

We studied the gene for Cu,Zn SOD in 15 German patients with familial ALS and did not find any mutation. Activity of the enzyme and its expression at the protein level was also normal in each patient and in 18 patients suffering from the sporadic form of ALS.

[Computed tomography of the skeletal muscles in neuromuscular diseases]. / Computertomographie der Skelettmuskulatur bei neuromuskulären Erkrankungen.

CT-documentation of skeletal muscular lesions caused by neuromuscular diseases implies an essential contribution to conventional techniques in the macroscopic field. Size, distribution and degree of lesions as well as compensatory mechanisms are proved thereby. We report about the different effects on muscle appearance referring to 106 patients of our own experience in amyotrophic lateral sclerosis, spinal muscular atrophy, poliomyelitis, polyradiculitis, polyneuropathy as well as peripheral traumatic nerve lesions.

[Technic for computed tomographic study of skeletal muscles in neuromuscular diseases]. / Technik computertomographischer Skelettmuskeluntersuchungen bei neuromuskulären Erkrankungen.

Computed tomography provides a complete view of morphological alterations in skeletal muscle caused by neuromuscular diseases. A good image quality of the lower as well as of the upper limbs is obtained by choosing a small scanning-field and an appropriate scanning-position. The arms are best examined one by one. In follow-up studies muscular atrophy can be documented by planimetric and densimetric measurements. Furthermore CT-scanning is a convenient method for selecting suitable muscles for muscle biopsy.

[MR-tomography and -spectroscopy of skeletal muscles using high magnetic field strengths]. / MR-Tomographie und -Spektroskopie der Skelettmuskulatur bei hohen Magnetfeldstärken.

Intact as well as neuromuscular affected skeletal muscles can be precisely analysed by MR tomography with high magnetic field strengths. The substitution of muscle by adipose tissue under atrophic conditions is seen most clearly in fat images, while the morphology of small structures is predominantly shown by water images. The aim of in-vivo spectroscopy is an identification and quantification of metabolites. A relative increase in the amount of adipose tissue within atrophic muscles was confirmed by the 1-H spectrum. As concluded from 13-C and 31-P spectra there was neither a change in adipose tissue composition nor a modification of energy metabolism.

Muscle stiffness and electrical activity in paramyotonia congenita.

To investigate the pathomechanism of paramyotonic stiffness, the mechanogram of isometric finger force and the electromyogram of the flexor digitorum muscle were simultaneously recorded in five unrelated paramyotonia congenita patients. Cooling of the forearm provoked "spontaneous" electrical activity, but the accompanying force was less than 5% of the maximal voluntary isometric contraction amplitude. The relaxation of maximal voluntary contractions executed in the cold had a normal first phase and a very slow second phase. The force amplitude at the beginning of the slow phase was up to 80% of the maximal contraction amplitude; the duration of the slow phase was up to several minutes. It was concluded that the slowed muscle relaxation is more important as a factor contributing to paramyotonic stiffness than spontaneous force generation. Involuntary electrical activity recorded during the slow relaxation phase was too low to account for the force. Intercostal muscle biopsies obtained from four patients showed similar phases of slow relaxation when stimulated to give isometric twitches or tetani in the cold. Extracellular recording with electrodes designed to pick up all activity from the small bundles clearly showed that the slow relaxation phase was not caused by spontaneous action potentials. One possible explanation for the slowed relaxation is a long-lasting depolarization-induced contracture of the muscle fibers following activation in the cold.

Hypokalemic periodic paralysis: in vitro investigation of muscle fiber membrane parameters.

To study the mechanism of attacks in familial hypokalemic paralysis, we recorded resting membrane potentials, action potentials, current-voltage relationships, and isometric forces in intercostal muscle fibers from three patients. In normal extracellular medium, the resting potential was reduced, but membrane conductance was not different from control. Excitability was reduced and the action potentials had no overshoot. On exposure to a 1-mM potassium solution, with or without insulin, the cells depolarized to about -50 mV, and became inexcitable. Over the tested membrane potential range from -120 to -40 mV, the slope conductance in the 1-mM potassium solution was not different from that of control fibers in a 1-mM potassium solution. In particular, the potassium component conductance was not reduced. Depolarized fibers could not be completely repolarized by returning to a 3.5-mM potassium solution. An experimentally induced transient shift of the chloride equilibrium potential to a highly negative value caused stable repolarization. Paralysis could also be induced by replacement of extracellular chloride with an impermanent anion, a treatment which causes myotonia in healthy fibers. It was concluded that the basic defects are a reduced excitability and an increased sodium conductance, and that these defects are aggravated on reduction of the extracellular potassium concentration.

Studies of the coding region of the neuronal glutamate transporter gene in amyotrophic lateral sclerosis.

Studies of the coding region of the neuronal glutamate transporter of 6 amyotrophic lateral sclerosis (ALS) patients and 10 controls show an identical pattern of four reported amino acid variations. No mutations and polymorphisms were detected in 5 sporadic ALS patients and a single patient with the familial form of the disease.

Adynamia episodica hereditaria with myotonia: a non-inactivating sodium current and the effect of extracellular pH.

To study the mechanism of periodic paralysis, we investigated the properties of intact muscle fibers biopsied from a patient who had adynamia episodica hereditaria with electromyographic signs of myotonia. When the potassium concentration in the extracellular medium, [K]e, was 3.5 mmol/l, force of contraction, membrane resting potential, and intracellular sodium activity were normal, but depolarizing voltage clamp steps revealed the existence of an abnormal inward current. This current was activated at membrane potentials less negative than -80 mV, reached a maximum within 50 msec, and was not inactivated with time. The inward current was completely and reversibly blocked by tetrodotoxin, which indicates that it was carried by sodium ions. In a solution containing 9 mmol/l potassium, normal muscle would depolarize to -63 mV and yet be capable of developing full tetanic force upon stimulation. The muscle from the patient depolarized to -57 mV and became inexcitable, i.e., it was paralyzed. A contracture did not develop. Lowering of the extracellular pH did not influence the resting potential, but it effectively antagonized or prevented the paralytic effect of high [K]e by changing the inactivation characteristics of the sodium channels. Hydrochlorothiazide, which had a therapeutic effect on the patient, did not prevent paralysis in vitro. An abnormal rise of the intracellular sodium activity was recorded when the extracellular potassium concentration was raised to 10 mmol/l.

[Diagnosis of susceptibility to malignant hyperthermia using the in vitro contracture test]. / Diagnose der Anlage zu Maligner Hyperthermie mit Hilfe des in vitro-Kontrakturtests.

Though a malignant hyperthermia (MH) crisis is still a critical event during general anesthesia, recent developments in prophylaxis and treatment should help in avoiding fatal episodes. The best means to avoid MH episodes would be early recognition of MH susceptibility. Today the only reliable test to identify MH susceptibility is the in vitro contracture test. Thus, to diagnose MH susceptibility we performed this test on muscle biopsies from 26 individuals who: (1) had an event during general anesthesia that may have been indicative of MH (4 patients); (2) had a family member with a medical history of MH (20 patients); or (3) had unexplained elevated CK levels (1 patient). The criteria according to which patients were submitted to the testing are shown in detail in Table 1. We used the standardized version of the contracture test that has been proposed by the European Malignant Hyperpyrexia Group. Muscle biopsies (20-30 mm long, 8 mm diameter) were dissected into 8-10 small bundles (2-3 mm diameter) and tested within 3 h post-biopsy in four independent tissue baths with various concentrations of caffeine or halothane. According to the concentration of caffeine or halothane necessary to elicit contractures exceeding a predefined force threshold (20 mN), it was possible to classify the patients as MHS (MH-susceptible), MHE (equivocal), or MHN (negative). In addition to the in vitro test, clinical, laboratory, and neurophysiological data were collected from these patients and correlated with the individual test results (Table 2). Thirteen patients were classified as MHS, five were MHE, and seven patients MHN (Fig. 3).(ABSTRACT TRUNCATED AT 250 WORDS)

The glial glutamate transporter complementary DNA in patients with amyotrophic lateral sclerosis.

Here, we report a mutation screening by single-stranded conformational analysis of the astroglial human brain glutamate transporter (HBGT) II complementary DNA in patients with amyotrophic lateral sclerosis. The conformational analysis data indicate a lack of sequence variations in the HBGT II coding region in 6 patients with amyotrophic lateral sclerosis and the same number of nonneurological control subjects. In both groups, three variants of the HBGT II 5' untranslated region were isolated. We have no evidence that the reported complementary DNA variants are disease specific.

Amyotrophic lateral sclerosis: macro-EMG and twitch forces of single motor units.

Macro-EMG potentials (MEP)s and twitch contractions (spike-triggered-averaging) of single motor units (MUs) have been recorded in the first dorsal interosseus muscle (FDI) of 10 control subjects and 20 patients with amyotrophic lateral sclerosis (ALS). MUs over the full range of voluntary recruitment thresholds were studied. Patients with slightly affected FDIs (5) mainly showed MUs with enlarged MEPs and increased twitch forces. In contrast, the patients with more severely affected FDIs (15) revealed decreased twitch forces, especially in the MUs with higher thresholds. The corresponding MEPs could be enlarged as well as normal. It appears that MU sprouting and the resulting increase of twitch force can compensate for the loss of motoneuron in early stages of ALS. In more advanced stages, however, a decline of the force of the surviving MUs, especially of those with higher thresholds, seems to contribute to the progressive muscle weakness, in addition to the corticospinal degeneration and the reduction in the number of motoneurons.

In vivo P-NMR spectroscopy: muscle energy exchange in paramyotonia patients.

Using phosphorus nuclear magnetic resonance spectroscopy, we studied the muscle metabolism in four patients with paramyotonia congenita as reflected in the PC/Pi and PC/ATP ratios. At normal body temperature, all results were indistinguishable from controls. After cooling to 29 degrees C muscle temperature and a single 2-sec maximum contraction, the forearm muscles were stiff. At this stage, no decrease in the ATP content could be detected. In greater than 50% of the experiments with patients, an additional peak occurred transiently at the resonant frequency for monophosphates. After a working period at 29 degrees C muscle temperature, the paramyotonic muscles were paralyzed, but displayed spectra similar to those obtained at normal body temperature and full working capability. Intracellular pH was close to 7 in paramyotonic muscle under all conditions examined.