For June 2015 we have selected: Menon P, Geevasinga N, Yannikas C, Howells J, Kiernan MC, Vucic S. Sensitivity and specificity of threshold tracking transcranial magnetic stimulation for diagnosis of amyotrophic lateral sclerosis: a prospective study. Lancet Neurology 2015;14:478-484.
The early diagnosis of amyotrophic lateral sclerosis (ALS) and its atypical phenotypes may be particularly challenging. To diagnose ALS, the El Escorial and the Awaji clinical and neurophysiological criteria are currently used, but the sensitivity of these criteria is considered overall unsatisfactory. It can be particularly difficult to identify signs of upper motor neuron (UMN) dysfunction. Transcranial magnetic stimulation (TMS) seems to be an emerging reliable technique to objectively evaluate the functional integrity of the UMN system. In particular, by using threshold tracking TMS technique, cortical hyperexcitability has been found to be a possible biomarker of early ALS (with progression to normal excitability or hypoexcitability within the evolution of the disease).
To assess the accuracy of the threshold tracking TMS technique in differentiating ALS from mimic neuromuscular disorders, Menon and colleagues prospectively studied a population of 281 patients with suspected ALS referred to three neuromuscular centers in Sydney, Australia. At time of recruitment patients underwent threshold tracking TMS (index test, STARD criteria) and clinical assessments according to the Awaji diagnostic criteria (reference standard, STARD criteria) to differentiate ALS from non-ALS. TMS examiners were masked to the results of reference test, investigations and history of the patients, whereas a separate rater did all data analysis. The diagnosis of ALS was eventually made in 209 patients (after a mean follow-up of 15.8 months), while 68 patients were diagnosed with non-ALS disorders. Threshold tracking TMS could differentiate ALS from non-ALS with a sensitivity of 73.21% (95% CI 66.66-79.08) and a specificity of 80.88% (69.53-89.40). Reduction of averaged short-interval intracortical inhibition (SICI, interstimulus interval 1-7 ms) was the most important diagnostic TMS variable.
“This study provides evidence of the utility of threshold tracking TMS in improving early diagnosis of ALS’, says Professor A. Ludolph, from the Department of Neurology of the Ulm University, Germany. “Indeed, an extra 34% of patients with ALS were early diagnosed using TMS compared to the Awaji criteria alone. Threshold tracking TMS seemed also to be useful in differentiating between patents with and without signs of UMN dysfunction and different ALS subtypes. Moreover, riluzole treatment did not interfere with the TMS sensitivity.”
“The early diagnosis of ALS is important for prompt riluzole treatment and, eventually, patient inclusion in other therapeutic clinical trials. As such, this study supports the use of threshold tracking TMS as an important complementary diagnostic tool’, states Professor V. Silani, from the Department of Neurology of the University of Milan Medical School, Milan, Italy. “However, the wide use of this specialized technique has obvious critical limitations, due to the technology itself, operator skills, and training. Further multicenter studies are needed to validate a broad utilize of this interesting technique.”
The other nominees for the June’s paper of the month are:
- Mons U, Muezzinler A, Gellert C, et al., for the CHANCES consortium. Impact of smoking and smoking cessation on cardiovascular events and mortality among older adults: meta-analysis of individual participant data from prospective cohort studies of the CHANCES consortium. British Medical Journal 2015;350:h1551 (doi:10.136/bmj.h1551): Data collected from 503,905 elderly subjects involved in European and USA cohorts show that smoking is a strong independent risk of cardiovascular events and mortality. However, smoking cessation reduces this related cardiovascular risk even at old age.
- Rapp SR, Case LD, Peiffer A, et al. Donepezil for irradiated brain tumor survivors: a phase III randomized placebo-controlled clinical trial. Journal of Clinical Oncolology 2015;33 (doi: 10.1200/JCO.2014.58.4508): 6-month treatment with donepezil was no effective in improving overall cognitive function in adult brain tumor survivors after radiotherapy. However, some individual cognitive domains significantly improved, especially in patients with greater pretreatment cognitive impairment.
- Machado GC, Maher CG, Ferreira PH, et al. Efficacy and safety of paracetamol for spinal pain and osteoarthritis: systematic review and meta-analysis of randomized placebo controlled trials. British Medical Journal 2014;350:h1225 (doi:10.1136/bmj.h1225): Data analyses from 13 randomized clinical trials indicate that paracetamol is unsuccessful in improving low back pain and quality of life, and slightly effective in improving hip or knee osteoarthritic pain in the short-term.
- The AVERT Trial Collaboration group. Efficacy and safety of very early mobilization within 24h of stroke onset (AVERT): a randomized controlled trial. Lancet Neurology April 17, 2015 (doi:10.1016/S0140-6736(15)60690-0: This study enrolled 2,104 patients from 56 acute stroke units in five countries. Compared to patients receiving the usual care, patients who received very early mobilisation, within 24 h after the stroke. had less favorable outcome in terms of little or no disability at 3 months. There was no difference in death or serious adverse events.