Shivam Mittal

Botulinum Toxin Treatment of Neuropathic Pain

Neuropathic pain (NP), a common form of human pain, often poorly responds to analgesic medications. In this review the authors discuss the pathophysiology and conventional treatment of neuropathic pain and provide evidenced-based statements on the efficacy of botulinum neurotoxins (BoNTs) in this form of pain. The level of efficacy for BoNT treatment in each category of NP is defined according to the published guidelines of the American Academy of Neurology. The data indicate that BoNT treatment (most of the literature is with onabotulinumtoxinA) is effective (level A evidence) in postherpetic neuralgia and trigeminal neuralgia. It is probably effective (level B) in posttraumatic neuralgia and painful diabetic neuropathy. The data on complex regional pain syndrome, carpal tunnel syndrome, occipital neuralgia, and phantom limb pain are preliminary and await conduction of randomized, blinded clinical trials. Much remains to be learned about the most-effective dosage and technique of injection, optimum dilutions, and differences among BoNTs in the treatment of neuropathic pain.

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.

Incobotulinum Toxin-A Improves Post-Surgical and Post-Radiation Pain in Cancer Patients.

Cancer patients who undergo surgery or radiation can develop persistent focal pain at the site of radiation or surgery. Twelve patients who had surgery or radiation for local cancer and failed at least two analgesic medications for pain control were prospectively enrolled in a research protocol. Patients were injected up to 100 units of incobotulinum toxin A (IncoA) intramuscularly or subcutaneously depending on the type and location of pain (muscle cramp or neuropathic pain). Two patients passed away, one dropped out due to a skin reaction and another patient could not return for the follow up due to his poor general condition. All remaining 8 subjects (Age 31–70, 4 female) demonstrated significant improvement of Visual Analog Scale (VAS) (3 to 9 degrees, average 3.9 degrees) and reported significant satisfaction in Patients’ Global Impression of Change scale (PGIC) (7 out of 8 reported the pain as much improved). Three of the 8 patients reported significant improvement of quality of life.

Tremors and Klinefelter’s Syndrome

Background Klinefelter’s syndrome (KS) has been associated with tremor, but reports on tremor phenomenology and treatment are limited. Case Reports Patient 1 is a 17-year-old male with a dystonic tremor treated with deep brain stimulation (DBS). Patient 2 is a 57-year-old male with a predominant left hand resting tremor and dystonic features. Discussion Our cases suggest that the tremor in patients with KS may be dystonic in nature. Patient 1 is also the third reported case of successful treatment with DBS. These cases have implications for elucidating the underlying neurobiological mechanism of tremor and identifying treatment options.

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.

Botulinum Toxin in Restless Legs Syndrome—A Randomized Double-Blind Placebo-Controlled Crossover Study

Background: Restless Legs Syndrome (RLS) is a common movement disorder with an estimated prevalence of up to 12%. Previous small studies with onabotulinumtoxin A (OnaA) for RLS have shown inconsistent results. Methods: Twenty-four patients with an International RLS score (IRLS) of >11 (moderate-severe) were enrolled in this blinded, placebo-controlled crossover study. Twenty-one patients completed the evaluations at 4, 6, and 8 weeks after each injection. One-hundred units of Incobotulinumtoxin A (IncoA) or normal saline were injected into tibialis anterior, gastrocnemius, and biceps femoris muscles each side. Results: Improvement from a severe (IRLS >21) to a mild/moderate (IRLS ≤20) score was significant at four weeks (p = 0.0036) and six weeks (p = 0.0325) following IncoA administration compared to placebo. Additionally, there was significant improvement in pain score at six weeks as measured by Visual Analogue Scale (p = 0.04) and the Johns Hopkins Quality of Life Questionnaire (p = 0.01) in the IncoA group. Definite or marked improvement on Patient Global Impression of Change was seen in 7 out of 21 patients in the IncoA group vs. 1 out of 21 patients in the placebo group at 4 weeks (p = 0.012). Conclusion: IncoA injection lead to a reduction in severity of RLS symptoms, pain score, and quality of life, without any adverse effects.

Teaching Neuro Images: Balamuthia mandrillaris amebic encephalitis : Clinical–radiologic–pathologic correlation

A 32-year-old immunocompetent man presented with new-onset generalized tonic-clonic seizures. On examination, he had mild right hand weakness, with right-sided Hoffman sign, ankle clonus, and Babinski reflex present. MRI of the brain demonstrated vasogenic edema surrounding a ring-enhancing lesion in the left parietal lobe (figure, A). Repeat brain MRIs showed rapid progression of the lesion, with new lesions appearing in the contralateral hemisphere (figure, B and C). Pathology showed necrotizing meningoencephalitis with organisms consistent with ameba (figure, D). Indirect immunofluorescence and PCR was positive for Balamuthia mandrillaris. About 200 cases of Balamuthia infection have been reported worldwide, and it has a very high mortality rate of 95%.1

Botulinum Toxin in Parkinson Disease Tremor

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.

Original articleBotulinum 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.

Hypocupremia: A Possible Association with Late Cortical Cerebellar Atrophy

Background We report a patient, diagnosed with late cortical cerebellar atrophy, who had persistent low serum copper levels. Case report A 48-year-old male developed progressive difficulty with balance, frequent falls, and dysarthric speech, which worsened over a short time span. He had an extensive ataxia work-up, which was unremarkable except for persistent low serum copper levels despite adequate supplementation. Magnetic resonance imaging of the brain showed marked cerebellar atrophy. The patient experienced progressive worsening of symptoms, which did not improve with either oral or parenteral copper supplementation. Discussion To our knowledge, ours is the first case report of late cortical cerebellar atrophy in the setting of low serum copper levels. The current report should trigger further research in mechanisms leading to copper deficiency and its possible role in cerebellar disease.