Greg Thaera

Are corticosteroid and antiviral treatments effective for bell palsy? A critically appraised topic.

Background:Bell palsy is idiopathic peripheral facial weakness that typically resolves without severe clinical sequelae. Treatment with corticosteroids and antiviral drugs is often initiated to improve the likelihood of a favorable outcome. Objective:Are corticosteroid and antiviral medications effective in the treatment of Bell palsy? Methods:The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario with a structured question, search strategy, critical appraisal, results, evidence summary, commentary, pre- and postassessment, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and a clinical content expert in the field of Otolaryngology. Results:The largest (18 trials involving 2786 patients) current systematic review and meta-analysis for pharmacologic treatment of Bell palsy was selected for appraisal. The meta-analysis demonstrated a clear benefit of oral corticosteroids, alone, in preventing unsatisfactory recovery of facial weakness (relative risk, 0.69 [95% confidence interval {CI}, 0.55–0.87], number needed to treat 11 [95% CI, 8–25]). Treatment with antiviral medication, alone, was not associated with a reduced risk of unsatisfactory recovery. When administered concurrently with corticosteroids, antiviral treatments displayed a trend toward reduced risk of unsatisfactory recovery, compared with corticosteroids alone (relative risk, 0.75 [95% CI, 0.56–1.00]). Conclusion:Corticosteroids effectively reduce the risk of an unfavorable outcome in Bell palsy. Antiviral agents, when administered concurrently with corticosteroids, may result in additional benefit.

Do Cannabinoids Reduce Multiple Sclerosis-Related Spasticity?

Background:The plant Cannabis sativa contains numerous cannabinoids, which are aromatic hydrocarbons that have central nervous system effects mediated through specific cannabinoid receptors. Some patients with multiple sclerosis (MS) report symptomatic relief from spasticity, pain, and other symptoms when using smoked cannabis, and small trials have suggested some symptomatic benefit. Objective:Do cannabinoids improve spasticity in patients with MS? Methods:We addressed the question through the development of a structured, critically appraised topic. Participants included consultant and resident neurologists, clinical epidemiologists, medical librarian, and clinical content experts in the field of MS. Participants started with a clinical scenario and a structured question, devised search strategies, located and compiled the best evidence, performed a critical appraisal, synthesized the results, summarized the evidence, provided commentary, and declared bottom-line conclusions. Results:The largest randomized, placebo-controlled trial of oral cannabinoid therapy detected no improvement for MS-related spasticity as measured by the Ashworth scale. However, subjective participant reports indicated improvement in spasticity (P = 0.01), spasms (P = 0.038), sleep quality (P = 0.025), and pain (P = 0.002) without detriment to depression, fatigue, irritability, or walk time. A second randomized controlled trial, which used subjective participant report as the primary outcome, revealed the same discrepancy between subjective and objective spasticity outcome measures. Conclusion:Randomized controlled trials have failed to confirm objective evidence for a beneficial effect of cannabinoids on MS-related spasticity. However, improvement in subjective assessments of spasticity and other related symptoms have been consistently noted, raising questions about the sensitivity and validity of current objective outcome instruments. Further research is warranted with regards to both outcome instrument development and the effects of cannabinoids on MS-related spasticity.

Is donepezil effective for multiple sclerosis-related cognitive dysfunction? A critically appraised topic.

Background:Cognitive dysfunction affects approximately half of the patients with multiple sclerosis (MS). Cholinesterase inhibitor drugs are approved to treat cognitive dysfunction associated with degenerative dementia. Objective:To critically assess current evidence regarding the efficacy of the cholinesterase inhibitor, donepezil in the treatment of MS-associated cognitive impairment. Methods:The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario, structured question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the fields of behavioral neurology and MS. Results:A randomized control trial was selected for critical appraisal. This trial randomized MS patients to receive donepezil 10 mg daily or placebo for treatment of MS-related cognitive dysfunction. There was no significant treatment effect found between the 2 groups on either the primary outcome of memory or any of the secondary cognitive measures. Post hoc analyses suggested a trend favoring donepezil in subjects with greater baseline cognitive dysfunction. Conclusions:Donepezil 10 mg daily for 24 weeks is not superior to placebo in improving MS-related cognitive dysfunction.

Positive neurologic phenomena with initiation of dalfampridine for multiple sclerosis

OBJECTIVE Review cases of positive neurologic phenomena initiated or worsened with dalfampridine in patients with multiple sclerosis. BACKGROUND Oral, extended release dalfampridine (4-aminopyridine or 4-AP) is a potassium-channel blocker approved for the treatment of gait impairment in multiple sclerosis (MS). The enhanced conduction along demyelinated axons promoted by dalfampridine could potentially lead to development of positive neurologic phenomena. METHODS We reviewed the medical records of patients who were started on dalfampridine for activation of positive sensory or motor symptoms. RESULTS Four of 76 patients (5.3%) developed positive sensory symptoms within one month of starting dalfampridine; one additional patient had new-onset seizure. Cessation of dalfampridine was insufficient to resolve symptoms in two patients with recurrent trigeminal neuralgia. CONCLUSIONS Initiation of dalfampridine may be associated with initiation or recurrence of positive sensory symptoms in patients with multiple sclerosis. The increased axonal conduction from potassium channel blockade may contribute to this exacerbation of positive sensory phenomena.

Teaching NeuroImages: Dyspnea as a presenting manifestation of amyloid myopathy

A 69-year-old man had dyspnea followed by slowly progressive proximal leg weakness over 2 years. He had macroglossia (figure 1). Creatine kinase was 1,378 U/L. A deltoid biopsy revealed myopathy, denervation atrophy, and congophilic deposits around perimysial vessels, indicating amyloid (figure 2). Further workup revealed serum monoclonal lambda protein, bone marrow amyloid, and cardiomyopathy. Amyloid myopathy, an underrecognized entity, predominantly presents with progressive proximal weakness in primary amyloidosis.1 Dyspnea results from cardiomyopathy or respiratory muscle weakness (our patient had both). Macroglossia due to amyloid deposition is a helpful clinical clue. The patient is on chemotherapy with cyclophosphamide, dexamethasone, and bortezomib, which improves prognosis in amyloidosis.2