Duarte Machado

Treatment of Refractory Pain with Botulinum Toxins—An Evidence-Based Review

OBJECTIVES To provide updated information on the role of botulinum toxins in the treatment of refractory pain based on prospective, randomized, double-blind, placebo-controlled studies. DESIGN OF THE REVIEW: Class I and class II articles were searched online through PubMed (1966 to the end of January 2011) and OvidSP including ahead-of-print manuscripts. RESULTS Level A evidence (two or more class I studies-established efficacy): pain of cervical dystonia, chronic migraine, and chronic lateral epicondylitis. Level B evidence (one class I or two class II studies-probably effective and recommended): post-herpetic neuralgia, post-traumatic neuralgia, pain of plantar fasciitis, piriformis syndrome, and pain in total knee arthroplasty. Level C evidence (one class II study-possibly effective, may be used at discretion of clinician): allodynia of diabetic neuropathy, chronic low back pain, painful knee osteoarthritis, anterior knee pain with vastus lateralis imbalance, pelvic pain, post-operative pain in children with cerebral palsy after adductor hip release surgery, post-operative pain after mastectomy, and sphincter spasms and pain after hemorrhoidectomy. Level U evidence (efficacy not proven due to diverse class I and II results): myofascial pain syndrome and chronic daily headaches. Studies in episodic migraine and tension headaches have shown treatment failure (level A-negative). CONCLUSION Evidence-based data indicate that administration of botulinum toxin in several human conditions can alleviate refractory pain. The problems with some study designs and toxin dosage are critically reviewed.

Tremor-related quality of life: A comparison of essential tremor vs. Parkinson's disease patients

BACKGROUND Tremor-related quality of life is a multi-dimensional concept that reflects the physical, emotional and other health effects of tremor. Curiously, tremor-related quality of life has never been directly compared in patients with the two major tremor disorders, essential tremor (ET) and Parkinsons disease (PD). We performed a head-to-head comparison of ET with PD patients. METHODS The Quality of Life in Essential Tremor (QUEST) questionnaire was administered to 103 ET and 103 matched PD patients enrolled in a clinical-epidemiological study in New York. RESULTS The QUEST total score and QUEST physical subscore were higher in ET than PD patients (both p < 0.05). In relative terms, ET patients reported significantly more impairment than PD patients in multiple areas; PD patients reported more impairment than ET patients in one area (all p ≤ 0.02). In absolute terms, tremor impacted on many aspects of quality of life in both diseases, including physical and psychosocial, and in one-third or more of PD patients, tremor sometimes, frequently or always interfered with numerous physical activities, including writing, using a typewriter/computer, fixing small things, dressing, eating, and holding reading material. CONCLUSIONS Tremor is a clinical entity that can have numerous effects on patients. While there were relative differences between the two major tremor disorders, ET and PD, in absolute terms, tremor impacted on several domains of quality of life, from physical to psychosocial, in a large proportion of ET and PD patients. Attempts to judge the efficacy of treatments for tremor, whether pharmacological or surgical, should consider its broad impact.

OnabotulinumtoxinA for Treatment of Focal Cancer Pain After Surgery and/or Radiation

OBJECTIVE To report the relief from refractory focal post-radiation and/or postsurgical cancer pain after local treatment with onabotulinumtoxinA. SETTING AND DESIGN We studied the effect of onabotulinumtoxinA in seven cancer patients who suffered from severe focal pain (visual analog scale >5) at the site of local surgery or radiotherapy or both. OnabotulinumtoxinA (20-100 units) was injected into the focal pain areas (skin or muscle or both). Five of seven patients were followed beyond 1 year (1.5-5 years) with repeat treatment. RESULTS All seven patients reported a significant improvement in pain (mean drop in visual analog scale score of 5.1). They described their response on the patient global assessment as satisfactory (two patients) or very satisfactory (five patients). Six of seven patients found the pain relief associated with significant improvement in quality of life. One patient developed weakness of jaw muscles after bilateral masseter injection that was not observed during second injection (reduced dose). Improvements with treatment persisted with repeat injections during long-term follow-up (five patients). CONCLUSION Local treatment with onabotulinumtoxinA can significantly reduce pain and improve quality of life in cancer patients suffering from pain in the area of surgery and radiation and was well tolerated in cancer patients.

Idiopathic hypertrophic pachymeningitis mimicking neurosarcoidosis.

The approach to a patient presenting with multiple cranial europathies is complex given the diverse number of causes includng neoplastic, vascular, traumatic, infectious, autoimmune and nflammatory etiologies. In cases where imaging reveals thickened ura with enhancement around multiple cranial nerves and no priary cause can be found, the diagnosis of idiopathic hypertrophic achymeningitis (IHP) is given [1–3]. Here we present the case of a atient with multiple worsening cranial neuropathies who underent extensive evaluation consistent with neurosarcoidosis, but hose dural biopsy revealed IHP.

Botulinum toxin in essential hand tremor - A randomized double-blind placebo-controlled study with customized injection approach

INTRODUCTION To evaluate the safety and efficacy of incobotulinumtoxinA (IncoA) injection for treatment of essential hand tremor. In essential tremor and Parkinsons disease tremor, administration of onabotulinumtoxinA via a fixed injection approach improves the tremor but a high percentage of patients (30-70%) develop moderate to severe hand weakness which has limited its use in clinical practice. METHODS This study was performed from July 2013 to July 2016 on 33 subjects. This is a double-blind, placebo-controlled, crossover trial injecting 80-120 units of IncoA into 8-14 hand and forearm muscles using a customized approach. The subjects were followed for 28 weeks. The treatment efficacy was evaluated by the Fahn Tolosa Marin tremor rating score and NIH genetic criteria for tremor severity at 4 and 8 weeks after each of the two sets of treatments. Hand strength was assessed by an ergometer. RESULTS There was statistically significant improvement in clinical rating score of tremor at 4 and 8 weeks following the IncoA injection. CONCLUSION In this study, injection of IncoA treatment via a customized approach improved essential tremor on the clinical scales and patients perception with a low occurrence of significant hand weakness.

Botulinum Toxin in Parkinson Disease Tremor: A Randomized, Double-Blind, Placebo-Controlled Study With a Customized Injection Approach

BACKGROUND In essential tremor and Parkinson disease (PD) tremor, administration of onabotulinumtoxinA via a fixed injection approach improves the tremor, but many patients (30%-70%) develop moderate to severe hand weakness, limiting the use of onabotulinumtoxinA in clinical practice. OBJECTIVE To evaluate the safety and efficacy of incobotulinumtoxinA (IncoA) injection for the treatment of tremor in PD. PATIENTS AND METHODS In this double-blind, placebo-controlled, crossover trial, 30 patients each received 7 to 12 (mean, 9) IncoA injections into hand and forearm muscles using a customized approach. The study was performed from June 1, 2012, through June 30, 2015, and participants were followed for 24 weeks. Treatment efficacy was evaluated by the tremor subsets of the Unified Parkinsons Disease Rating Scale and the Patient Global Impression of Change 4 and 8 weeks after each of the 2 sets of treatments. Hand strength was assessed using an ergometer. RESULTS There was a statistically significant improvement in clinical rating scores of rest tremor and tremor severity 4 and 8 weeks after the IncoA injection and of action/postural tremor at 8 weeks. There was a significant improvement in patient perception of improvement at 4 and 8 weeks in the IncoA group. There was no statistically significant difference in grip strength at 4 weeks between the 2 groups. CONCLUSION Injection of IncoA via a customized approach improved PD tremor on a clinical scale and patient perception, with a low occurrence of significant hand weakness. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT02419313.

Abobotulinum Toxin A in the Treatment of Chronic Low Back Pain

Chronic low back pain is a debilitating condition with a complex and multifactorial pathophysiology. Botulinum neurotoxins (BoNTs) have strong analgesic effects, as shown in both animal models of pain and in human beings. A randomized, double-blind, placebo-controlled, parallel format study to investigate the efficacy of abobotulinum toxin A (aboA) in chronic low back pain was conducted. The study cohort consisted of 18 patients who received 100 units of aboA into each of the five lumbar extensor spinae muscles unilaterally or bilaterally (total dose 500 to 1000 units), and 19 who received normal saline of the same volume. The level of pain and quality of life were assessed using the visual analogue scale (VAS) and three questionnaires including the Oswestry Low Back Pain Disability Questionnaire (OLBPDQ). Patients’ perception of improvement was recorded via patient global impression of change (PGIC). The primary outcome measure, the proportion of responders with VAS of <4 at 6 weeks, was not met, but the data was significantly in favor of aboA at 4 weeks (p = 0.008). The total Oswestry score representing quality of life improved in the aboA group compared to the placebo group (p = 0.0448). Moreover, significantly more patients reported their low back pain as “much improved” in the abobotulinum toxin A group (0.0293).

Public Knowledge and Attitude toward Essential Tremor: A Questionnaire Survey.

Background Public awareness of and attitude toward disease is an important issue for patients. Public awareness of essential tremor (ET) has never been studied. Methods We administered a 10-min, 31-item questionnaire to 250 consecutive enrollees. These included three samples carefully chosen to have a potential range of awareness of ET: 100 individuals ascertained from a vascular disease clinic, 100 individuals from a general neurology clinic, and 50 Parkinson’s disease (PD) patients. Results Leaving aside PD patients, only 10–15% of enrollees had ever heard of or read about “ET.” Even among PD patients, only 32.7% had ever heard of or read about ET. After providing enrollees with three synonymous terms for ET (“benign tremor,” “kinetic tremor,” “familial tremor”), ~40% of non-PD enrollees and 51.0% with PD had ever heard or read about the condition. Even among participants who had heard of ET, ~10% did not know what the main symptom was, 1/3 were either unsure or thought ET was the same disease as PD, 1/4 thought that ET was the same condition as frailty- or aging-associated tremor, 2/3 attributed it to odd causes (e.g., trauma or alcohol abuse), only 1/3 knew of the existence of therapeutic brain surgery, fewer than 1/2 knew that children could have ET, and 3/4 did not know of a celebrity or historical figure with ET. Hence, lack of knowledge and misconceptions were common. Conclusion Public knowledge of the existence and features of ET is overall poor. Greater awareness is important for the ET community.

Orofacial dyskinesia after moxifloxacin treatment--a case with normal hepatorenal function and review of literature.

BackgroundOrofacial dyskinesia is rarely reported with antibiotics. Among antibiotics, third-generation fluoroquinolones are known to cause movement disorders. We report the first patient who developed orofacial dyskinesia after taking a fourth-generation fluoroquinolone, namely, moxifloxacin. MethodsThe patient is a 58-year-old woman who was treated with moxifloxacin for acute bronchitis. She developed orofacial dyskinesia involving the tongue, lips, and facial muscles after treatment. ResultsDiscontinuation of moxifloxacin and treatment with clonidine resulted in significant reduction of orofacial dyskinesia over the period of 8 to 12 weeks. A review of literature shows reports of a variety of involuntary movements with third-generation fluoroquinolones, mostly manifesting in patients with impaired renal and kidney function. ConclusionsThe fourth-generation fluoroquinolone moxifloxacin can cause orofacial dyskinesia like third-generation fluoroquinolone antibiotics and in a patient with normal renal and liver function.

Clinical Use of Botulinum Neurotoxins: Pain

Animal data have shown that botulinum neurotoxins (BoNTs) inhibit the release of pain neurotransmitters/neuromodulators (glutamate, substance P, calcitonin-gene-related peptide) and pro-inflammatory agents (prostaglandins, bradykinin, histamine) from peripheral nerve endings and sensory ganglia and reduce the phenomena of peripheral and central sensitization, major factors for pain chronicity. A review of class I and II studies (double blind, placebo controlled) using the criteria set forward by the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology shows different levels of efficacy for a large number of human pain disorders: There exists level A evidence (two or more class I studies—established efficacy) for pain of cervical dystonia, chronic migraine and chronic lateral epicondylitis and level-B evidence (one class I or two class II studies—probably effective) for postherpetic and posttraumatic neuralgia, pain of plantar fasciitis, piriformis syndrome and pain in total knee arthroplasty. Level C evidence (one class II study—possibly effective) denotes allodynia of diabetic neuropathy, chronic low back pain, painful knee osteoarthritis, anterior knee pain with vastus lateralis imbalance, pelvic pain, postoperative pain in children with cerebral palsy after adductor hip release surgery, postoperative pain after mastectomy and sphincter spasms and pain after hemorrhoidectomy. The myofascial pain syndrome and chronic daily headaches have level U evidence (efficacy not proven due to controversial results). Results of BoNT treatment trials in episodic migraine and chronic tension headaches justify level A evidence for treatment failure. The end of each assessed category includes a medical comment and suggestions for improvement of future studies. For certain pain syndromes, figures are provided to illustrate the suggested number and site of injections and the appropriate doses.