Strength in Parkinson's disease: Relationshp to rate of force generation and clinical status

Maximum elbow flexor and extensor muscle strength was measured in 9 patients with Parkinson's disease on and off antiparkinsonian medication. In addition, the rate of force generation, the rate of actively returning force to resting levels, and passive release of force “relaxation” were measured in submaximal contractions. The measures of strength and contraction time were correlated with changes in clinical status as measured by the Unified Parkinson's Disease Rating Scale. When patients were off medication, their reduction in strength was significantly greater in extension than flexion. The reduction in flexion strength did not reach statistical significance. The extensor weakness was primarily due to decreased tonic activation of the extensor muscles and not to muscle coactivation. Muscle relaxation time was much more prolonged than was force generation time or active force return time. The increase in relaxation time and the decrease in extensor strength both correlated with changes in clinical status. Finally, changes in extensor torque correlated with the time to actively return force, suggesting that reduced strength is related to a reduced ability to generate rapid contractions in some patients with Parkinson's disease. These results suggest that there is an asymmetric distribution of muscle weakness in Parkinson's disease and that selected measures of muscle strength and muscle relaxation correlate with changes in clinical status.     

Focal myopathy mimicking posterior interosseous nerve syndrome.

A 25-year-old man developed weakness of extension of the right index, middle, and fourth fingers at the metacarpophalangeal joints, over 2 years. No sensory deficit was present. Nerve conduction studies, including the right radial nerve, were within normal limits. Needle electromyographic (EMG) examination showed myopathic changes that were limited to the right extensor digitorum communis and extensor indicis proprius muscles. An intravenous edrophonium chloride test had no effect on weakness and repetitive stimulation showed no significant decremental response. An EMG-guided open biopsy of the extensor digitorum communis muscle revealed severe myopathic changes. Evaluation for the cause of myopathic involvement was negative. After 13 months, clinical examination and electrophysiological studies showed no significant progression. This case exemplifies the fact that a focal myopathy may mimic an entrapment neuropathy.     

Adult-onset nemaline myopathy: Another cause of dropped head.

A 59-year-old man with severe neck extensor weakness had findings diagnostic of nemaline myopathy on muscle biopsy. Review of the literature shows that dropped head occurs in nearly half of the patients with adult-onset nemaline myopathy. Other leading causes of dropped head syndrome are amyotrophic lateral sclerosis, myasthenia gravis, and isolated neck extensor myopathy.     

Treatment of occupational cramp with botulinum toxin: Diffusion of toxin to adjacent noninjected muscles

Over a 5-year period, 40 patients, 11 with musician's and 29 with writer's cramp, were treated with botulinum toxin A using a precise injection technique in which the hollow-bore electromyography (EMG) needle was positioned by both standard EMG and by muscle twitch evoked by stimulating current passed through it. Moderate to complete improvement in dystonia occurred in 28 patients (70%) after the first injection and in 34 patients (85%) after the second injection with better outcome in nonmusicians than in musicians. Of note, weakness of uninjected muscles, immediately adjacent to those injected, was found in 25/40 patients (63%). The most common patterns of toxin spread were from flexor digitorum sublimis to profundus, extensor carpi radialis to extensor digitorum communis, and extensor indicis proprius to extensor pollicis brevis. Spread to, and weakness of, adjacent uninjected muscles was a major factor contributing to suboptimal outcome in 6/39 (15%) such patients. © 1997 John Wiley & Sons, Inc. Muscle Nerve, 20, 593–598, 1997.     

Parkinsonism and neck extensor myopathy: a new syndrome or coincidental findings?

BACKGROUND: Dropped head in parkinsonism has been attributed to dystonia or unbalanced muscle rigidity. To our knowledge, isolated neck extensor myopathy with parkinsonism has been described in only one patient. OBJECTIVES: To assess the occurrence of neck extension weakness resulting in dropped head in patients with parkinsonism and to explore whether the head drop might be the consequence of neck extensor myopathy. PATIENTS AND METHODS: All patients who were evaluated because of parkinsonism in the Department of Neurology in our hospital between January 1, 1997, and December 31, 1999, and were found to have both parkinsonism and neck extension weakness resulting in head drop were studied. The patients underwent clinical examination, blood tests including the levels of creatine kinase and myoglobin and neurophysiological evaluation with needle electromyography and autonomic tests. Open biopsy on a neck muscle was performed in the patients who could cooperate. RESULTS: Of 459 patients evaluated because of parkinsonism, 7 were found to have neck extensor weakness resulting in head drop. Needle electromyography revealed myopathic changes in all 7 patients. Muscle biopsy, which was performed in 5 patients, disclosed myopathic changes in all 5 patients. Electron microscopy revealed mitochondrial abnormalities in 2 of these 7 patients. Three of the patients had concomitant neck rigidity that could contribute to the neck position. All 7 patients had autonomic dysfunction and 6 responded poorly to levodopa therapy, making a diagnosis of multiple system atrophy probable. CONCLUSION: Parkinsonism may be associated with isolated neck extensor myopathy resulting in dropped head, and this condition should be suggestive of multiple system atrophy.     

Reciprocal Ia inhibition in spastic paralysis in man.

Reciprocal reflex connections were studied in capsular hemiplegia and spastic paresis with spinal cord lesions, using Lloyd's technique. Effects of conditioning stimulation of the tibial or peroneal nerve on the H reflex in the antagonists were examined. Stimulus intensity was controlled with reference to the threshold of the M wave. Weaker stimulation than this threshold was regarded as stimulation of group I afferents. It aroused no subjection sensation in intact subjects. Early and strong inhibition, comparable to Ia inhibition in the cat (Lloyd 1946), was observed from weak stimulation of the tibial nerve on the pre-tibial (flexor) H reflex, but not from the peroneal nerve on the triceps surae (extensor) H reflex in capsular hemiplegia. Alcohol block of extensor motor points resulted in reduction of spasticity without further paralysis in the blocked muscle and a remarkable increase in strength of the antagonist pre-tibial muscles. These results suggest that an extensor spasticity withe flexor weakness, which is common in capsular hemiplegia, may be due to an imbalance of reflex activities via Ia muscle afferents, and that a part of flexor weakness can be restored by "disinhibition' by reduction of Ia inflow from extensor muscles. Ia inhibition was also observed in one third of cases with spinal cord lesions at rest. It returned to normal after recovery from spastic paresis by radical therapy in some cases.     

Two patients with 'Dropped head syndrome' due to mutations in LMNA or SEPN1 genes

Dropped head syndrome is characterized by severe weakness of neck extensor muscles with sparing of the flexors. It is a prominent sign in several neuromuscular conditions, but it may also be an isolated feature with uncertain aetiology. We report two children in whom prominent weakness of neck extensor muscles is associated with mutations in lamin A/C (LMNA) and selenoprotein N1 (SEPN1) genes, respectively. This report expands the underlying causes of the dropped head syndrome which may be the presenting feature of a congenital muscular dystrophy.     

Early or late appearance of "dropped head syndrome" in amyotrophic lateral sclerosis

BACKGROUND: "Dropped head syndrome" caused by neck extensor weakness has been reported in a variety of neuromuscular disorders. Previously published reports include isolated cases with amyotrophic lateral sclerosis (ALS). In this report, nine patients with ALS and dropped head syndrome seen during a 20 year period are described. PATIENTS AND INVESTIGATIONS: Between 1981 and 2000, 683 patients with ALS were diagnosed, based on El Escorial criteria. Nine of these had profound neck extensor weakness observed as an early feature, or developing during the later stages of the disease. The protocol for evaluation included detailed clinical history, neurological examination, electromyography, and nerve conduction studies. Investigations were undertaken to exclude malignancy, lymphoproliferative disorders, thyroid dysfunction, and collagen vascular disease. RESULTS: The incidence of dropped head syndrome was 1.3%. The mean (SD) age of the affected patients was 53.3 (10.3) years (range 33 to 65), with an equal distribution of cases in the fourth to seventh decades. In six patients, head drop was an early feature (mean interval from onset of illness 11.6 months (range 3 to 24)); in three it was late (between three and eight years after onset). In five patients, mild neck flexor weakness was present in addition to severe extensor weakness. In all nine patients there were diffuse upper and lower motor neurone signs. None of the patients had difficulty in breathing but all had difficulty in swallowing and social embarrassment, both of which could be corrected by simple measures. CONCLUSIONS: Dropped head syndrome is an important clinical sign and usually occurs as an early feature within the first one to two years after the onset of ALS. The cause of dropped head syndrome in these nine cases could be easily established as ALS by the presence of generalised signs.     

Musk-antibody positive myasthenia gravis presenting with isolated neck extensor weakness

Dropped head sign is characterized by the gradual forward sagging of the head due to weakness of neck extensor muscles. This may be a prominent sign of several neuromuscular disorders and may be an isolated feature of myasthenia gravis (MG). We describe a patient with isolated neck extensor weakness, eletrophysiological findings suggesting myasthenia gravis and positive MuSK antibodies. This case supports that finding anti-MuSK antibodies may be extremely helpful in dropped head patients and negative acetylcholine receptor antibodies especially if needle EMG does not reveal myopathic or neurogenic patterns.     

Muscle weakness in respiratory and peripheral skeletal muscles in a mouse model for nebulin-based nemaline myopathy

Nemaline myopathy is among the most common non-dystrophic congenital myopathies, and is characterized by the presence of nemaline rods in skeletal muscles fibers, general muscle weakness, and hypotonia. Although respiratory failure is the main cause of death in nemaline myopathy, only little is known regarding the contractile strength of the diaphragm, the main muscle of inspiration. To investigate diaphragm contractility, in the present study we took advantage of a mouse model for nebulin-based nemaline myopathy that we recently developed. In this mouse model, exon 55 of Neb is deleted (Neb^ΔExon55), a mutation frequently found in patients. Diaphragm contractility was determined in permeabilized muscle fibers and was compared to the contractility of permeabilized fibers from three peripheral skeletal muscles: soleus, extensor digitorum longus, and gastrocnemius. The force generating capacity of diaphragm muscle fibers of Neb^ΔExon55 mice was reduced to 25% of wildtype levels, indicating severe contractile weakness. The contractile weakness of diaphragm fibers was more pronounced than that observed in soleus muscle, but not more pronounced than that observed in extensor digitorum longus and gastrocnemius muscles. The reduced muscle contractility was at least partly caused by changes in cross-bridge cycling kinetics which reduced the number of bound cross-bridges. The severe diaphragm weakness likely contributes to the development of respiratory failure in Neb^ΔExon55 mice and might explain their early, postnatal death.     

Concomitant dermatomyositis and myasthenia gravis presenting with respiratory insufficiency

We report a 28-year-old woman with a history of chronic immune-mediated hepatitis, in whom the simultaneous manifestation of dermatomyositis and myasthenia gravis resulted in severe neck extensor weakness and subacute respiratory insufficiency, followed by proximal muscle weakness and external ophthalmoplegia. Radiological signs of a thymoma were absent. The distinguishing clinical, electrophysiological, and biopsy findings are discussed. We suggest that an underlying immunoregulatory disorder was present, explaining the occurrence of three rare immune-mediated diseases in one patient.     

Relationship between various clinical signs in lesions of the descending motor system (a statistical study)

Classical upper motor neuron disease findings weakness, hypertonus, hyperreflexia, clonus and decreased skill), in patients with lesions of the descending motor system as manifested by extensor plantar responses, were statistically analyzed to determine if there was a relationship between them. In the upper extremity a highly significant relationship existed between weakness and decreased skill (p<0.005). In the lower extremity a highly significant relationship was noted between hyperreflexia and clonus (p<0.005) and a significant relationship existed between weakness and hypertonus (0.025>p>0.010). No statistically significant relationship was noted between the other findings in either the upper or the lower extremity.     

The dropped head syndrome.

We describe four patients with a neuromuscular syndrome characterized by relatively isolated neck extensor weakness. EMG and muscle biopsies suggest a restrictive noninflammatory myopathy predominantly affecting the cervical paraspinal muscles.     

Botulinum toxin type A in cerebellar tremor caused by multiple sclerosis

The intention tremor seen in chronic progressive multiple sclerosis is often disabling and existing treatments are of limited benefit The present pilot study was designed to assess the role of Botulinum toxin type A (BOTOX®) in such cases. Five patients with the condition received 40 mouse units of toxin into the flexor and extensor compartments of the forearm. Two of these went on to receive a further 100 mouse units 2 months after the previous injection. Tremor was assessed at 0, 2 and 8 weeks post-injection using a validated clinical rating scale, spirography and handwriting samples, and a clinician's global rating scale; functional capacity was measured using an activities of daily living (ADL) scale adapted for use in tremor. No statistically significant improvement occurred in intention tremor, although there was a trend toward a mild improvement in the clinician's global rating scale. Patients noted an increase in their pre-existing corticospinal weakness which proved to be dose-limiting. No change occurred in ADL scores. It is concluded that pre-existing weakness limits the use of Botulinum toxin in the intention tremor seen in multiple sclerosis, but further work in disabling primary and secondary cerebellar degenerations without corticospinal weakness may be worthwhile.     

Periodicities in the rate of on-demand electrical stimulation of the mesencephalic reticular formation to maintain wakefulness.

The effect of chronic administration of corticosteroids on the contractile properties of muscle has not been studied despite the regular occurrence of skeletal muscle weakness and atrophy in steroid myopathy. Two muscles, the predominantly fast-twitch-glycolytic extensor digitorum longus and the predominantly slow-twitch-oxidative soleus muscle of rabbits, were studied to determine if there is a differential effect dependent on the fiber type composition of the muscle. The fast-twitch-glycolytic extensor digitorum longus showed a loss of muscle mass associated with an alteration in contractile properties manifested by slower relaxation. The slow-twitch-oxidative soleus muscle was relatively unaffected by steroid treatment. Isometric contraction in the longus muscle was weaker in the treated animals but showed normal strength when measurements were normalized by comparing contractile data based on the cross-sectional area of the control and treated muscles. The findings suggest the possibility that the alteration in contractile properties could be related to changes in myosin or other contractile protein components of the fast-twitch-glycolytic extensor digitorum longus muscle. Changes in sarcoplasmic reticulum, although less likely, are not excluded by the present data.     

Dystrophia myotonica. Peripheral nerve involvement and pathogenetic implications.

A comparative electrophysioloical study of patients with dystrophia myotonica and control subjects is presented. The study includes estimation of the number of motor axons innervating the extensor digitorum brevis muscle and measurements of the conduction of M- and F-waves along the deep peroneal nerve. There is unequivocal electrophysiological evidence of nerve involvement in the disease. This was indicated by (a) prolongation of the terminal latencies and slowing of the motor conduction of the deep peroneal nerve (P less than 0.001), (b) delayed conduction of the F-wave along the proximal segments of the nerves (P less than 0.02-0.01), (c) reduced number of motor axons innervating the extensor digitorum brevis muscle (P less than 0.001), (d) high amplitude motor unit potentials and discrete EMG activity on the maximal volitional contraction of minimally affected muscles in one patient. However, if the muscle changes were secondary to the nerve involvement occurring in the disease, one would expect that the electrophysiological findings of neuropathy would become more prominent in patients with severe muscle wasting and weakness. Our results showed that in some patients with marked muscle atrophy and weakness there was no evidence of nerve involvement while in other patients with slight to moderate degree of muscle weakness the electrophysiological studies indicated peripheral neuropathy. Therefore, it appears that both the nerves and the muscles are independently affected by the pleiotropic action of the responsible gene and the evidence does not suggest that the muscle atrophy of patients with dystrophia myotonica is entirely neural.     

Influence of physiotherapeutic facilitation techniques on motor evoked potentials in centrally paretic hand extensor muscles

In the rehabilitation of stroke patients, various facilitation techniques are applied to reduce weakness in centrally paretic muscles and to improve functional motor capacity. The present investigation compared the facilitatory effect of 5 different physiotherapeutic approaches onto the centrally paretic extensor carpi radialis muscle in 30 stroke patients classified into 3 groups according to the individual degree of paresis. In order to quantify the influence of the respective facilitation manoeuvre, single transcranial magnetic stimuli were applied before and during the application of cutaneous/proprioceptive stimuli, a weight bearing task, contraction of the affected and the non-affected extensor carpi radialis muscle and during proximal preinnervation on the affected side. All procedures, indeed, enhanced the frequency of occurrence of muscular response potentials and their amplitudes while diminishing their response latencies. The most prominent effects were observed when the muscle itself was voluntarily activated. A similarly strong facilitation was obtained in the most severely affected patients with cutaneous and proprioceptive stimuli, but such stimuli had inhibitory effects in the healthy control group. The present study illustrates the interaction of cortically evoked motor potentials with peripherally or centrally generated inputs, contributes to the understanding of the neurophysiological mechanisms underlying physiotherapeutic facilitation techniques and helps in providing rational criteria to decide about the most appropriate facilitation method.     

Vulnerability of lower brachial myotomes in motor neurone disease: A clinical and single fibre EMG study

Single fibre EMG was used to study the motor unit fibre density in the right biceps brachii, extensor digitorum communis and first dorsal interosseous muscles of 15 patients with motor neurone disease, with different patterns of initial weakness. There was an inverse relationship between strength and fibre density in these muscles. Abnormalities were more marked in patients whose initial symptom was arm weakness, but collateral reinnervation was not as effective as in other neurogenic disorders. These findings are consistent with a hypothesis that motor neurone disease begins segmentally, or at a discrete level within the motor system, before becoming generalised. The single fibre EMG fibre density is a useful quantitative technique for sequential assessment of patients with neurogenic disorders.     

线状体肌病的临床及超微病理学特征(附1例报道)

目的探讨线状体肌病的临床特点、病理学特征。方法结合近3年国外文献复习,分析1例线状体肌病患者的临床特点和超微病理学特征。结果患者3岁发病,症状逐渐加重,病程逾20年,表现为典型的肌张力减低和肢体无力,症状以双下肢为主,近端和远端同时受累,伸肌为著,远端为甚,肌萎缩明显;病理检查发现线状小体、肌膜皱缩、肌纤维断裂,α和β颗粒以及一小块变性的神经纤维束。结论线状体肌病可累及全身骨骼肌,临床表现为肌张力减低和肌无力,病理学特征为线状小体。     

Bradykinesia,muscle weakness and reduced muscle power in Parkinson's disease

Muscle power (force × velocity) could clarify the relationship between weakness and bradykinesia in Parkinson's disease (PD). The aims of this study were to determine if patients with PD were weaker and/or less powerful in their leg extensor muscles than a neurologically normal control group and to determine the relative contributions of force and movement velocity/bradykinesia to muscle power in PD. Forty patients with PD and 40 controls were assessed. Strength in Newtons (N) was measured as the heaviest load the participant could lift. Power in Watts (W) was measured by having the participant perform lifts as fast as possible. The PD group were 172 N weaker (95% CI 28–315) and 124 W less powerful at peak power (95% CI 32–216) than controls. However, velocity at maximal power was only reduced compared with controls when lifting light to medium loads. When lifting heavy loads bradykinesia was no longer apparent in the PD group. These results suggest that reduced muscle power in PD at lighter loads arises from weakness and bradykinesia combined, but at heavier loads arises only from weakness. The absence of bradykinesia in the PD group when lifting heavy loads warrants further investigation. © 2009 Movement Disorder Society