Paper of the Month

For September 2018, we have selected:  Katzenschlager R, Poewe W, Rascol O, et al. Apomorphine subcutaneous infusion in patients with Parkinson’s disease with persisten motor fluctuations (TOLEDO): a multicenter, double-blind, randomized, placebo-controlled trial. Lancet Neurol July 25, 2018. doi:10.1016/S1474-4422(18)30284-4. Subcutaneous infusion of apomorphine, a potent dopamine receptor agonist, is widely used in patients with Parkinson’s disease (PD) with motor fluctuations not optimally controlled with oral medication, but the previous evidence base to support this approach was weak, derived from open label studies.

For August 2018, we have selected: Corvol JC, Artaud F, Cornier-Dequaire F, et al., for the DIGPD Study Group. Longitudinal analysis of impulse control disorders in Parkinson disease. Neurology 2018. doi:10.1212/WNL.0000000000005816. Impulse control disorders (ICDs) are frequent in Parkinson’s disease (PD) patients, and can have relevant consequences on social life. Whereas the association between treatment with dopamine agonists (DA) and the onset of ICDs is well known, there is controversy about the relationship with dose and duration of DA therapy.

For July 2018, we have selected: Thomalla G, Simonsen CZ, Boutitie G, et al., for the WAKE-UP Investigators. MRI-guided thrombolysis for stroke with unknown time of onset. NEJM May 16, 2018. doi:10.1056/NEJMoa1804355. Thrombolysis is currently performed in patients with acute ischemic stroke within a window of 4.5 hours since the symptoms’ onset. In about one third of the patients, the exact time of stroke onset is unknown, like in patients who wake up from sleeping.

For May 2018, we have selected: Kappos L, Bar-Or A, Cree BAC, et al., for the EXPAND Clinical Investigators. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomized, phase 3 study. Lancet Neurol 2018;391:1263-1273. Secondary progressive multiple sclerosis (SPMS) is characterized by a previous history of relapsing remitting MS (RRMS) and the continuous progression of disability over the years typically without relapses.

For April 2018, we have selected: Whelan CD, Altmann A, Botia JA, et al., for the ENIGMA-Epilepsy Working Group. Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study. Brain 2018;141:391-408. Epilepsy affects 0.6-1.5% of the population worldwide with one-third of patients being resistant to antiepileptic treatment. Nowadays epilepsy is considered a network disorder in which several structural changes are involved.

by Elena Moro For March 2018, we have selected: Honig LS, Vellas B, Woodward M, et al. Trial of solanezumab for mild dementia due to Alzheimer’s disease. N Engl J Med 2018;378:321-330. Alzheimer’s disease (AD) pathology can be related to either excessive production or reduced elimination of beta amyloid (Aβ), which eventually results in oligomers, fibrils, and neuritic Aβ plaques.

For February 2018, we have selected: Feneberg E, Oeckl P, Steinacker P, et al. Multicenter evaluation of neurofilaments in early symptom onset amyotrophic lateral sclerosis. Neurology 2018;90:e22-30. doi:10.1212/WNL.0000000000004761. Amyotrophic lateral sclerosis (ALS) is a devastating neurological disorder affecting motor neurons. The course of the disease is progressive with life span of 3 to 5 years from the onset of the symptoms.

For January 2018, we have selected: Mendell JR, Al-Zaidy S, Shell R, et al. Single-dose gene-replacement therapy for spinal muscular atrophy. NEJM 2017;377:1713-1722. Spinal muscular atrophy (SMA) is caused by loss or dysfunction of the gene encoding survival motor neuron 1 protein (SMN1). Disease severity is also influenced by a second gene, SMN2, which can produce smaller amounts of this protein.

For December 2017, we have selected: Dwivedi R, Ramanujam B, Chandra PS, et al. Surgery for drug-resistant epilepsy in children. NEJM 2017;377:1639-1647. Drug-resistant epilepsy can be particularly devastating in children due to the heavy impact on psychosocial aspects and quality of life of these little patients and their family.

For November 2017, we have selected: Mittal S, Bjørnevik K, Im DS, et al. ß2-Adrenoreceptor is a regulator of the α-synuclein gene driving risk of Parkinson’s disease. Science 2017;140:2295-2305. Disturbed proteostasis of α-synuclein is now thought to play a critical role in the pathogenesis of Parkinson’s disease (PD). Physiological functions of this protein include synaptic transport as well as involvement in the metabolism of membrane phospholipids, and in the differentiation and survival of dopaminergic neurons.

For October 2017, we have selected: Andersen G, Hedermann G, Witting N, Duno M, Andersen H, Vissing J. The antimyotonic effect of lamotrigine in non-dystrophic myotonias: a double-blind randomized study. Brain 2017;140:2295-2305. Patients with myotonia congenita and paramyotonia congenita can be disabled by the myotonic phenomenon in the activities of daily living, with a huge impact on their quality of life.

For September 2017, we have selected: Hoffman EM, Watson JC, St Sauver J, Staff NP, Klein CJ. Association of long-term opioid therapy with functional status, adverse outcomes, and mortality among patients with polyneuropathy. JAMA Neurology 2017;74:773-779. Neuropathic pain is a common symptom in polyneuropathy that can be difficult to manage. Opioids are usually recommended as second-line treatment, with primary care physicians being mainly involved in opioid prescription.

or August 2017, we have selected: The Writing Group on behalf of the Edaravone (MCI-186) ALS 19 Study Group. Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: a randomized, double-blind, placebo-controlled trial. Lancet Neurol 2017;16:505-512. There is evidence that oxidative stress induced by free radicals is a key factor of progression in amyotrophic lateral sclerosis (ALS).