Intramuscular injections of botulinum toxin for the treatment of upper back myofascial pain syndrome: A systematic review of randomized controlled trials.

BACKGROUND AND OBJECTIVE: Myofascial pain syndrome (MPS) is a chronic musculoskeletal disorder characterized by the presence of trigger points. Among the treatment options, botulinum toxin injections have been investigated. The aim of this paper was to provide a synthesis of the evidence on intramuscular botulinum toxin injections for upper back MPS. DATABASES AND DATA TREATMENT: A systematic review of the literature was performed on the PubMed, Scopus and Cochrane Library, using the following formula: ("botulinum") AND ("musculoskeletal") AND ("upper back pain") OR ("myofascial pain"). RESULTS: Ten studies involving 651 patients were included. Patients in the control groups received placebo (saline solution) injections, anaesthetic injections + dry needling or anaesthetic injections. The analysis of the trials revealed modest methodological quality: one "Good quality" study, one "Fair" and the other "Poor". No major complications or serious adverse events were reported. Results provided conflicting evidence and did not demonstrate the superiority of botulinum toxin over comparators. Most of the included trials were characterized by a small sample size, weak power analysis, different clinical scores used and non-comparable follow-up periods. Even if there is no conclusive evidence, the favourable safety profile and the positive results of some secondary endpoints suggest a potentially beneficial action in pain control and quality of life. CONCLUSION: The currently available studies show conflicting results. Their overall low methodological quality does not allow for solid evidence of superiority over other comparison treatments. Further insights are needed to properly profile patients who could benefit more from this peculiar injective approach. SIGNIFICANCE: The randomized controlled trials included in this review compared using botulinum toxin to treat upper back MPS with placebo or active treatments (e.g., dry needling or anaesthetics) showing mixed results overall. Despite the lack of clear evidence of superiority, our study suggests that the use of botulinum toxin should not be discouraged. Its safety profile and encouraging results in pain control, motor recovery and disability reduction make it an interesting treatment, particularly in the subset of patients with moderate to severe chronic pain and active trigger points. To support the safety and efficacy of botulinum toxin, further high-quality studies are needed.

ERIGO: a possible strategy to treat orthostatic hypotension in progressive supranuclear palsy? A feasibility study.

Progressive supranuclear palsy (PSP) is a neurodegenerative disease of the central nervous system, presenting with different clinical phenotypes, all involving the extrapyramidal system. Orthostatic hypotension (OH) is a common symptom of cardiovascular autonomic dysfunction. OH is defined as a fall in systolic blood pressure of at least 20 mmHg and/or a fall in diastolic blood pressure of at least 10 mmHg on standing or head-up tilt. In this pilot study, we tested the feasibility and efficacy of the ERIGO® device in managing OH non-responsive to conventional treatments in a sample of patients with PSP. OH was chosen as the primary outcome, as the symptom is a serious complication in neurodegenerative disorders, challenging the rehabilitation treatment. Six patients received intensive training using ERIGO®, a robot- assisted tilt table with an integrated leg movement system that allows progressive verticalization of the patient, and application of functional electrical stimulation. In all the participants, OH improved after the training with the device, suggesting that robotic verticalization may be a feasible and effective tool in improving blood pressure stability in patients with PSP. Further studies in larger samples, also including patients with other neurodegenerative disorders associated with OH, are needed to confirm these promising results.

Augmentative and alternative communication improves quality of life in the early stages of amyotrophic lateral sclerosis.

This study aimed to evaluate the efficacy of low-tech augmentative and alternative communication (AAC) aids in improving quality of life (QoL) and mood disorders, as well as the psychosocial impact of assistive devices, in 10 patients affected by amyotrophic lateral sclerosis (ALS) in the early stage of the disease, when speech difficulties appear. The AACtraining (AAC-T) study lasted around six months and comprised two phases of three months each: AAC-intervention (AAC-I) followed by AAC-familiarization (AAC-F). All the patients were assessed at the beginning (T0) and at the end (T1) of AAC-I, as well as at the end of AAC-F (T2). During the AAC-I phase, we applied a three-phase AAC intervention model to evaluate intelligibility of language, participation patterns, communication needs and adaptation to the AAC tools. All the patients showed a gradual and significant improvement, especially in acceptance of the AAC aids, mood and QoL. Moreover, a reduction of caregiver burden was noted. Our study has demonstrated the utility of the AAC aids also in the early stages of the disease in patients with ALS presenting with dysarthria. In our opinion, AAC-T may act as a bridge between the initial and later phases of the disease, when patients need to use high-tech aids, including an eye-tracking communication device. In conclusion, in this study we highlighted how early AAC-T in patients with ALS may be a valuable tool to demonstrate how specific strategies and low-technology aids can improve QoL of these patients and their caregivers, also decreasing stress and depression.

Multiple sclerosis and non-dystrophic myotonias: do they share a common pathophysiology?

Some patients with multiple sclerosis (MS) complain of symptoms, such as myokymia, myotonia, spasms, and stiffness, which have been demonstrated to be due to a concurrent non-dystrophic myotonia, i.e. myotonia congenita or paramyotonia congenita. Beyond the known casual association between MS and non-dystrophic myotonia, a channelopathy representing a primary trait of MS rather than an epiphenomenon of demyelization (i.e., an acquired channelopathy) may exist. Indeed, the finding of MS patients with no genetic evidence of non-dystrophic myotonia but showing a clinical picture resembling this condition would support this hypothesis. Thirty patients with MS and no concurrent diagnosis of myotonia congenita or paramyotonia congenita were submitted to the Fournier protocol. Some of these MS patients presented abnormal muscle excitability with scarce myotonic discharges, but only a few of them had clinical features compatible with myotonia congenita or paramyotonia congenita syndromes. Even though the low number of recruited patients did not allow a robust statistical analysis, our data seemed to indicate the presence of an ion channel dysfunction that is independent of the acquired channelopathies and likely represents a common pathophysiological mechanism underlying a unique channelopathy simultaneously involving the peripheral and the central nervous system in individuals with MS. Confirming the presence of such a primary channelopathy in MS patients is of non-negligible importance, since dysfunction of ion channels may represent a suitable therapeutic target in MS.

TRPV4 related scapuloperoneal spinal muscular atrophy: Report of an Italian family and review of the literature.

Scapuloperoneal spinal muscular atrophy (SPSMA) is a rare autosomal dominant disorder caused by heterozygous mutations in the transient receptor potential cation channel (TRPV4) gene, characterized by progressive scapuloperoneal atrophy and weakness. Additional features, such as vocal cord paralysis, scoliosis and/or arthrogryposis, are likely to occur. We report the first Italian family with SPSMA, harboring the c.806G>A mutation in TRPV4 gene (p. R269H). The pattern of expression was variable: the father showed a mild muscular involvement, while the son presented at birth skeletal dysplasia and a progressive course. We reinforce the concept that the disease can be more severe in the following generations. The disorder should be considered in scapuloperoneal syndromes with autosomal dominant inheritance and a neurogenic pattern. The presence of skeletal deformities strongly supports this suspicion. An early diagnosis of SPSMA may be crucial in order to prevent the more severe congenital form.

Long-term follow-up in infantile-onset lambert-eaton myasthenic syndrome.

Lambert-Eaton myasthenic syndrome is a neuromuscular junction disorder characterized by proximal limb muscle weakness, fatigability, decreased deep-tendon reflexes, and autonomic symptoms. There are 2 forms of Lambert-Eaton myasthenic syndrome: one most frequently associated with small-cell lung cancer (P-Lambert-Eaton myasthenic syndrome) and the other that is a pure autoimmune form (NP-Lambert-Eaton myasthenic syndrome). Lambert-Eaton myasthenic syndrome is a very rare disorder in children younger than age 12 years. Herein, we report a 25-year-old man with NP-Lambert-Eaton myasthenic syndrome, which onset was at the age of 10 years. To date, this is the most long-term follow-up of NP-Lambert-Eaton myasthenic syndrome in childhood. In our patient, the only symptomatic treatment with 3,4-diaminopyridine phosphate has been sufficient to guarantee him a good quality of life. Our data remind physicians to keep in mind the diagnosis of Lambert-Eaton myasthenic syndrome in children with a proximal myopathic pattern and they confirm the specificity of compound muscle action potential incremental pattern after brief maximal effort in Lambert-Eaton myasthenic syndrome.

ANT1 is reduced in sporadic inclusion body myositis.

To investigate ANT1 and NF-κB expression in inclusion body myositis (IBM) muscle and to verify their possible roles in the pathogenesis of the disease, we collected muscle samples from five patients with IBM, polimyositis (PM) and controls. p65 form of NF-κB was analyzed using immunocytochemistry, Western blot and EMSA. Western blot of ANT1 was performed and confirmed by gene expression study. Mann-Whitney test was used for groups comparisons. NF-κB (p65) was found over-expressed both with western blot and EMSA, either in IBM or PM patients versus controls (p < 0.01). Expression of ANT1 were lower in IBM samples versus both PM and controls (p < 0.01). ANT1 reduction and NF-κB over-expression in IBM muscle could explain the lack of apoptosis in such disease. Normal ANT1 expression in PM could be related to the scarcity of mitochondrial abnormalities in the disease, but it could also suggest that these two conditions diverge in activating different anti-apoptotic pathways.

A new explanation for recessive myotonia congenita: exon deletions and duplications in CLCN1.

OBJECTIVE: To assess whether exon deletions or duplications in CLCN1 are associated with recessive myotonia congenita (MC). METHODS: We performed detailed clinical and electrophysiologic characterization in 60 patients with phenotypes consistent with MC. DNA sequencing of CLCN1 followed by multiplex ligation-dependent probe amplification to screen for exon copy number variation was undertaken in all patients. RESULTS: Exon deletions or duplications in CLCN1 were identified in 6% of patients with MC. Half had heterozygous exonic rearrangements. The other 2 patients (50%), with severe disabling infantile onset myotonia, were identified with both a homozygous mutation, Pro744Thr, which functional electrophysiology studies suggested was nonpathogenic, and a triplication/homozygous duplication involving exons 8-14, suggesting an explanation for the severe phenotype. CONCLUSIONS: These data indicate that copy number variation in CLCN1 may be an important cause of recessive MC. Our observations suggest that it is important to check for exon deletions and duplications as part of the genetic analysis of patients with recessive MC, especially in patients in whom sequencing identifies no mutations or only a single recessive mutation. These results also indicate that additional, as yet unidentified, genetic mechanisms account for cases not currently explained by either CLCN1 point mutations or exonic deletions or duplications.

Acetazolamide efficacy in hypokalemic periodic paralysis and the predictive role of genotype.

OBJECTIVES: Acetazolamide has been the most commonly used treatment for hypokalemic periodic paralysis since 1968. However, its mechanism of efficacy is not fully understood, and it is not known whether therapy response relates to genotype. We undertook a clinical and genetic study to evaluate the response rate of patients treated with acetazolamide and to investigate possible correlations between response and genotype. METHODS: We identified a total of 74 genotyped patients for this study. These included patients who were referred over a 15-year period to the only U.K. referral center or to a Chinese center and who underwent extensive clinical evaluation. For all genotyped patients, the response to acetazolamide therapy in terms of attack frequency and severity was documented. Direct DNA sequencing of CACNA1S and SCN4A was performed. RESULTS: Only 46% of the total patient cohort (34 of 74) reported benefit from acetazolamide. There was a greater chance of benefit in patients with mutations in CACNA1S (31 responded of 55 total) than in those with mutations in SCN4A (3 responded of 19 total). Patients with mutations that resulted in amino acids being substituted by glycine in either gene were the least likely to report benefit. CONCLUSIONS: This retrospective study indicates that only approximately 50% of genotyped patients with hypokalemic periodic paralysis respond to acetazolamide. We found evidence supporting a relationship between genotype and treatment response. Prospective randomized controlled trials are required to further evaluate this relationship. Development of alternative therapies is required.