Toward the validation of a new method (MUNIX) for motor unit number assessment.

INTRODUCTION: This prospectively designed study analyzed the correlation of a new, non-invasive neurophysiological method (Motor Unit Number Index - MUNIX) with two established Motor Unit Number Estimation (MUNE) methods. METHODS: MUNIX and incremental stimulation MUNE (IS-MUNE) were done in the abductor digiti minimi muscle (ADM), while MUNIX and spike-triggered averaging MUNE (STA-MUNE) were tested in the trapezius muscle. Twenty healthy subjects and 17 patients with amyotrophic lateral sclerosis (ALS) were examined. RESULTS: MUNIX and MUNE values correlated significantly (ADM: n=108; Spearman-Rho; r=0.88; p<0.01; trapezius muscle: n=49; Spearman-Rho; r=0.46; p<0.01). DISCUSSION: MUNIX indeed reflects the number of motor units in a muscle, and may sensibly be recorded from the trapezius muscle. With MUNIX being both much more patient friendly and much more rapid to assess than MUNE, the results support the use of MUNIX when motor unit number assessment is desired.

Discharge rates in electromyography distinguish early between peripheral and central paresis.

INTRODUCTION: Abnormally increased discharge rates (DRs) of motor unit potentials on concentric needle electromyography (CNEMG) indicate a loss of motor units in peripheral neurogenic lesions. METHODS: To determine when increased DRs occur during the course of a peripheral nerve lesion, we retrospectively analyzed CNEMG recordings of 19 patients with acute weakness of peripheral origin. RESULTS: The initial CNEMG studies took place from 3.7 hours to 10 days after the onset of the lesion. Abnormally increased DRs (≥20/s) were found in all but 1 of the muscles in which MRC grade was <4. Peripheral neurogenic damage was confirmed in all patients thereafter. The DRs depended on neither the kind of lesion nor the time between onset and CNEMG examination. CONCLUSIONS: The measurement of DRs of motor unit potentials is helpful immediately after a sudden paresis of MRC grade 3 or worse to differentiate between a central and a peripheral lesion.

Differentiation between uniform and non-uniform motor nerve conduction slowing.

OBJECTIVE: Demyelination may cause a uniform reduction of the conduction velocity of all fibres of a peripheral nerve segment, or may affect only certain nerve fibres in a non-uniform way while sparing others. This study was done to improve the detection of non-uniform conduction slowing by using the high-frequency attenuation (HFA) method. METHODS: Nerve conduction data from patients with early inflammatory demyelinating neuropathy (non-uniform demyelination, n=20), hereditary neuropathy (uniform demyelination, n=9), motor neuron disease (axon loss, n=20), and from healthy control subjects (n=20) were analysed. RESULTS: HFA, compound muscle action potential (CMAP) amplitude decay, and F-wave chronodispersion correlated significantly. Among these variables both HFA and amplitude decay most sensitively identified non-uniform demyelination (35%). In the patients with uniform demyelination, the most frequent finding was a reduced nerve conduction velocity (NCV) (100%). The most specific marker of non-uniform demyelination was HFA. For uniform demyelination it was NCV. CONCLUSIONS: The pattern of correlations between the variables studied confirms that NCV and F-min are indicators of uniform conduction slowing. HFA, amplitude decay, and F-wave chronodispersion indicate non-uniform conduction slowing, for which HFA is both sensitive and specific. SIGNIFICANCE: The HFA method improves both the diagnostic sensitivity and specificity of nerve conduction studies in patients with non-uniform demyelination.

Use of botulinum toxin A in adult neurological disorders: efficacy, tolerability and safety.

The protein botulinum neurotoxin A (BoNT/A) is one of seven distinct neurotoxins produced by Clostridium botulinum. BoNT/A blocks cholinergic synapses with an extremely high specificity and potency. Appropriately purified and diluted, BoNT/A serves as a reliable and well tolerated drug that is applied by local injection.The efficacy of BoNT/A is evident in the symptomatic therapy of disorders in which muscular hyperactivity plays a prominent role, such as focal dystonias and hemifacial spasm; in these disorders, BoNT/A is considered first-line therapy. BoNT/A is also beneficial in the treatment of both adults and children with spasticity of various causes. The pain that frequently accompanies these conditions is effectively reduced by BoNT/A. A genuine analgesic effect for BoNT/A unrelated to skeletal muscle spasmolysis has been suggested on the basis of in vitro and in vivo (animal) data. However, studies in humans designed to detect such an effect were negative, as were controlled studies of BoNT/A in patients with primary headache disorders.BoNT/A also acts on cholinergic synapses of the autonomic nervous system, and injection of BoNT/A into salivary glands significantly decreases the production of saliva. This may be beneficial for patients with Parkinson's disease, in whom the excessive production of saliva may be problematic.Overall, BoNT/A has been confirmed as an efficacious, predictable and well tolerated drug in an ever-increasing number of neurological disorders.

Botulinum toxin A does not alter capsaicin-induced pain perception in human skin.

A genuine peripheral antinociceptive and anti-inflammatory effect of Botulinum neurotoxin type A (BoNT/A) has been proposed but could not be demonstrated in humans so far. Therefore, 100 mouse units of Botulinum toxin A (Dysport) and placebo were injected in a double blind paradigm in defined skin areas of 50 subjects. At baseline and after 4 and 8 weeks allodynia was induced in the skin areas with capsaicin ointment. Heat and cold pain threshold temperatures were measured with quantitative sensory testing, and threshold intensities upon electrical stimulation with a pain specific surface electrode were determined. No BoNT/A related differences in pain perception were found at any quality. There is neither a direct peripheral antinociceptive effect nor a significant effect against neurogenic inflammation of BoNT/A in humans.

Treatment of chronic tension-type headache with botulinum toxin A: a randomized, double-blind, placebo-controlled multicenter study.

A beneficial effect of botulinum toxin on tension-type headache was reported in open-label studies but scientifically rigorous clinical studies are lacking. Therefore we conducted a prospective, multicenter, randomized, double-blind, placebo-controlled trial. Multiple pericranial muscles of 112 patients with chronic tension-type headache were treated either with 500 mouse units of botulinum toxin (Dysport) or with placebo. The diagnoses were made strictly following the International Headache Society criteria. Co-existence of migraine was an exclusion criterion. Injections were made following a fixed scheme and not adjusted to the patient's symptoms. Patients kept a headache diary that was used to calculate the area under the headache curve of 6 weeks before and 12 weeks after the treatment as the main effect measure. Secondary effect measures were the number of days with headache, the number of days with intake of analgesics, the duration of the nocturnal sleep, and the Beck Depression Inventory score. There were no significant differences between the verum group and the placebo group in any of these variables. Seven patients of the verum group had transient weakness of the eyelids, the neck, or both, indicating that a higher dose than used in this study does not seem sensible for the treatment of headache. The statistical power of the study was high enough to warrant the conclusion that there is no clinically significant effect of botulinum toxin A on chronic tension-type headache.

Increased metabolic muscle fatigue is caused by some but not all mitochondrial mutations.

CONTEXT: Excessive muscle fatigue occurs in patients with a mitochondrial encephalomyopathy (MEM), but it is also a frequent problem in patients with other neuromuscular disorders (ONMD). OBJECTIVE: To determine whether, and to what extent, metabolic muscle fatigue specifically occurs in patients with an MEM. DESIGN: Metabolic muscle fatigue was assessed in a series of 21 patients with an MEM, including 13 patients with chronic progressive external ophthalmoplegia and 8 patients with various mitochondrial point mutations; 27 patients with ONMD; and 25 healthy controls. Isometric twitch force of the ankle dorsiflexors was measured after supramaximal stimulation of peroneal nerves. Six trains of stimuli (of 1 minute's duration with rates from 0.2 to 5 stimuli per second) were given to each subject. RESULTS: An abnormal decrement of the twitch amplitude that occurred during a stimulation train was found in patients with MEM and in those with ONMD. The decrement of the twitch amplitude of controls and of patients with ONMD was strongly influenced by their muscle force (P<.001). After subtraction of the influence of the muscle force, specific fatigue was notably higher in patients with chronic progressive external ophthalmoplegia than in patients with ONMD and in controls, and it correlated well with elevations of serum lactate. Specific fatigue was also abnormal in a patient with a mitochondrial G7497A mutation, but normal in patients with an A3243G or a G11778A mutation. The heteroplasmy of mitochondrial DNA in muscle correlated neither with the force measures nor with the serum lactate levels. CONCLUSIONS: Generally, metabolic muscle fatigue accompanies muscular weakness. Specifically, some but not all mitochondrial mutations cause excessive metabolic muscle fatigue.

Botulinum toxin A and the cutaneous nociception in humans: a prospective, double-blind, placebo-controlled, randomized study.

Aside from temporary chemodenervation of skeletal muscle and potential anti-inflammatory effects, a genuine peripheral antinociceptive effect of Botulinum Neurotoxin Type A (BoNT/A) has been suspected. To evaluate the effect of BoNT/A on cutaneous nociception in humans, 50 healthy volunteers received subcutaneous injections of 100 mouse units (MU) BoNT/A (Dysport) and placebo. Both forearms of each subject were treated in a double-blind fashion, one with verum, one with placebo. Heat and cold pain thresholds within the treated skin areas were measured with quantitative sensory testing (QST) and pain thresholds were evaluated with local electrical stimulation (ES). The tests were done before treatment, and after 4 and 8 weeks. No major side effects were noted. All participants completed the study. Heat and cold pain thresholds increased from baseline to week 4 by 1.4 degrees C for verum and by 1.1 degrees C for placebo. From baseline to week 8, the thresholds increased by 2.7 degrees C for verum and by 1.2 degrees C for placebo. Electrically induced pain thresholds shifted from baseline to week 4 by -0.07 mA for verum and by 0.01 mA for placebo. From baseline to week 8, the thresholds increased by 0.10 mA for verum and by 0.11 mA for placebo. None of these differences was statistically significant. The study shows that there is no direct peripheral antinociceptive effect of BoNT/A in humans. The efficacy of BoNT/A in various pain syndromes must be explained by other pathways such as chemodenervation or anti-inflammatory effects.