Progesterone and its derivatives for the treatment of catamenial epilepsy: A systematic review.

OBJECTIVE: Catamenial epilepsy (CE) is defined as an increase in seizure frequency during specific phases of the menstrual cycle in women with epilepsy. The treatment usually includes a combination of non-hormonal and hormonal therapies. This systematic review summarizes the available data on the efficacy of progesterone and its derivates to treat CE. METHODS: We performed a systematic search of the literature to identify studies reporting data on the use of progesterone and its derivatives (any type and dose) for the treatment of CE. The main outcome included the efficacy of progesterone and its derivatives on seizure frequency. RESULTS: Nineteen articles (457 patients) were included; four were randomized controlled trials (two comparing progesterone vs placebo and two comparing norethisterone vs placebo). Progesterone was generally administered during the luteal phase (from day 15 to 25) or during perimenstrual exacerbations (from day 23 to 25), with an average dose of 10-30 mg/day to a maximum of 300 mg/day. The therapy, usually well tolerated, was ineffective in the randomized controlled trials; conversely, it was associated with an overall reduction in seizure frequency in case reports and uncontrolled studies. CONCLUSIONS: Although data from uncontrolled studies suggest that hormone therapy with progesterone may be useful in the treatment of CE, its efficacy has not been demonstrated in controlled trials. The possible antiseizure effect of progesterone could be mediated by its active metabolite allopregnanolone, making the plasmatic measurement of these hormones mandatory to evaluate efficacy. Further randomized controlled trials should investigate the efficacy of progesterone and its derivatives, addressing these pharmacological issues.

Aristotle - Ἀριστοτέλης (ARISTOTÉLES, 384/3- 322/1 BCE) The revelation of tuberculosis in his zoological works.

One of the most challenging issues with the sources of ancient medicine is to be able to identify the correspondence between the diseases we know today and those reported in ancient medical texts. Ancient diseases' definitions rarely help us, and the symptoms described often correspond to more than one disease. This is especially true about tuberculosis, a disease that historians of medicine habitually associates with the Greek words phthi(n)o (φθίνω), verb, phthisis/phthoe (φθίσις/φθόη), noun, phthinodes/phthisikos (φθινώδης/φθισικός), adjective, all etymologically linked to an Indo-European root that expresses the idea of consumption in a broad sense. This article aims to analyze a group of Greek words, branchos/branchia (ßράγχος/ßράγχια), krauros/kraurao (κραῦρος/κραυράω), and katarreo (καταρρέω), that appear in nosological contexts very close to the infectious disease that today we call tuberculosis. Moreover, the paper aims to focus on the transmission pathways of TB being via animal-human contact and some ancient strategies to cure it. The symptoms, transmission pathways and therapeutic approach of tuberculosis belong to a homogeneous pathological picture that emerges from a set of texts that date back to the period between the fifth century BC and the second century AD.

Voices from the past: The pioneering use of the phonograph in neurology.

Since its discovery by the American inventor and industrialist Thomas Alva Edison (1847-1931) in 1877, the phonograph attracted much interest in the field of medicine. This article describes the earliest pioneering examples of the use of the phonograph in neurology. In France, the use of the phonograph for obtaining audio recordings of delusions and speech or language disturbances was first proposed by Victor Maurice Dupont (1857-1910) in 1889 and in Italy by the physician Gaetano Rummo (1853-1917), who had studied at La Salpêtrière under Jean-Martin Charcot (1825-1893). The applicability of the phonograph to the record of speech disturbances was illustrated in England by John Hughlings Jackson (1835-1911) and William Halse Rivers (1864-1922), and by William Hale White (1857-1949) and Cuthbert Hilton Golding-Bird (1848-1939) in 1891. Since then, audio recordings have been used rarely in neurology, a branch of medicine where the visual aspects dominate, to the extent that inspection can be enough to reach a definite clinical diagnosis. In the mid-20th century, the advent of audio and video recordings supplanted audio recordings alone, relegating them to a very marginal role.

Digital therapeutics in neurology.

Digital therapeutics (DTx) is a section of digital health defined by the DTx Alliance as "delivering evidence-based therapeutic interventions to patients that are driven by software to prevent, manage, or treat a medical disorder or disease. They are used independently or in concert with medications, devices, or other therapies to optimize patient care and health outcomes". Chronic disabling diseases could greatly benefit from DTx. In this narrative review, we provide an overview of DTx in the care of patients with neurological dysfunctions.

New anti-seizure medication for elderly epilepsy patients - a critical narrative review.

Introduction: The number of elderly patients with epilepsy is growing in resource rich countries due to demographic changes and increased longevity. Management in these patients is challenging as underlying etiology, co-morbidities, polypharmacy, age-related pharmacokinetic and pharmacodynamic changes need to be considered.Areas covered: Lacosamide, eslicarbazepine acetate, brivaracetam, and perampanel have been approved in the USA and Europe for monotherapy and/or adjunctive treatment of seizures in the last few years. The authors review the pharmacological properties and safety profile of these drugs and provide recommendations for their use in in the elderly.Expert opinion: There are only limited data available on more recent antiseizure medications (ASMs). Drugs with a low risk of interaction (lacosamide, brivaracetam) are preferred choices. Once daily formulations (perampanel and eslicarbazepine acetate) have the advantage of increased compliance. Intravenous formulations (brivaracetam and lacosamide) are useful in emergency situations and in patients who have difficulties to swallow. Dose adjustments are necessary for all ASMs used in the elderly with slow titration and lower target doses than in the regulatory trials. The adverse event profile does not significantly differ from that found in the general adult population.

A cross-sectional survey among physicians on internet use for epilepsy-related information.

OBJECTIVE: We investigated views towards the Internet in a sample of Italian healthcare specialists involved in epilepsy field, to identify factors associated with the attitude of being influenced by information found on the Internet. METHODS: This study was a self-administered survey conducted in a group of members of the Italian Chapter of the International League Against Epilepsy (ILAE) in January 2018. RESULTS: 184 questionnaires were analyzed. 97.8 % of responders reported to seek online information on epilepsy. The Internet was most frequently searched to obtain new information (69.9 %) or to confirm a diagnostic or therapeutic decision (37.3 %). The influence of consulting the Internet on clinical practice was associated with registration to social network(s) (OR: 2.94; 95 %CI: 1.28-6.76; p = 0.011), higher frequency of Internet use (OR: 3.66; 95 %CI: 1.56-9.21; p = 0.006) and higher confidence in reliability of online information (OR: 2.61; 95 %CI: 1.09-6.26; p = 0.031). No association was found with age, sex, years in epilepsy practice or easiness to find online information. CONCLUSION: Internet is frequently used among healthcare professionals involved in the epilepsy to obtain information about this disease. The attitude of being influenced by the Internet for diagnostic and/or therapeutic decisions in epilepsy is independent on age and years of experience in epilepsy, and probably reflects an individual approach towards the Web.

Increased risk of epilepsy in patients registered in the Swedish Dementia Registry.

BACKGROUND AND PURPOSE: Data on epilepsy in dementia, particularly on its risk factors, are scarce. Confounding comorbidities and the rising incidence of epilepsy in older age have hampered studies in this field. The occurrence and risk factors for epilepsy in the Swedish Dementia Registry (SveDem), a large cohort of patients with dementia, have been examined. METHODS: Information on epilepsy and seizure-related diagnoses, comorbidities and survival were extracted for all individuals in SveDem (n = 81 192) and three randomly selected age- and gender-matched controls from the population register, excluding all with a dementia diagnosis (n = 223 933). The risk of epilepsy following dementia diagnosis was estimated with Kaplan-Meier curves, and Cox proportional hazard modelling was used to identify risk factors and adjust for comorbidities. RESULTS: A diagnosis of epilepsy was found more frequently amongst dementia patients [4.0%, 95% confidence interval (CI) 3.8-4.1] than controls (1.9%, 95% CI 1.9-2.0). The risk of incident epilepsy after dementia was 2.1% (95% CI 1.9-2.3) at 5 years and 4.0% (95%CI 3.4-4.6) at 10 years, compared to 0.8% (95% CI 0.8-0.8) and 1.6% (95% CI 1.4-1.8) respectively for controls. The risk was greatest for early-onset Alzheimer's disease. In multivariate analysis, dementia was associated with a hazard ratio of 2.52 (95% CI 2.31-2.74) for epilepsy. Young age, male sex, stroke, brain trauma, brain tumour and low Mini-Mental State Examination score significantly increased the risk. CONCLUSIONS: Dementia, particularly young-onset Alzheimer's disease, increases the risk of subsequent epilepsy. Further studies are needed to determine optimal management and the impact of epilepsy on prognosis.

Cannabidiol as adjunctive treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome.

Epilepsy is one of the most common chronic disorders of the brain affecting around 70 million people worldwide. Treatment is mainly symptomatic, and most patients achieve long-term seizure control. Up to one-third of the affected subjects, however, are resistant to anticonvulsant therapy. Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) are severe, refractory epilepsy syndromes with onset in early childhood. Currently available interventions fail to control seizures in most cases, and there remains the need to identify new treatments. Cannabidiol (CBD) is the first in a new class of antiepileptic drugs. It is a major chemical of the cannabis plant, which has antiseizure properties in absence of psychoactive effects. This article provides a critical review of the pharmacology of CBD and the most recent clinical studies that evaluated its efficacy and safety as adjunctive treatment of seizures associated with LGS and DS.

Randomized controlled trials of antiepileptic drugs for the treatment of post-stroke seizures: A systematic review with network meta-analysis.

OBJECTIVE: To determine the best available evidence on the efficacy and tolerability of antiepileptic drugs (AEDs) used to treat poststroke seizures and epilepsy. METHODS: MEDLINE, Embase, CENTRAL, ClinicalTrials.gov and Opengrey.eu were searched for RCTs of AEDs used to treat post-stroke epilepsy. The following outcomes were considered: seizure freedom; occurrence of adverse effects (AEs); withdrawal for AEs. The methodological quality was assessed according to the Cochrane Handbook for Systematic Reviews of Interventions. Adjusted indirect comparisons were made between each AED using controlled-release carbamazepine (CR-CBZ) as common comparator. RESULTS: Only 2 RCTs were included, one comparing levetiracetam (LEV) with CR-CBZ and the other comparing lamotrigine (LTG) with CR-CBZ. No significant difference was found in seizure freedom between either LEV or LTG and CR-CBZ. Occurrence of AEs were lower for LEV and LTG than for CR-CBZ. Indirect comparisons showed no difference between LEV and LTG for seizure freedom (OR 0.86; 95%CI: 0.15-4.89). Occurrence of AEs was higher for LEV than for LTG (OR 6.87; 95%CI: 1.15-41.1). For withdrawal rates due to AEs, we found a large width and asymmetrical distribution of confidence intervals around the obtained OR of 10.8 (95% CI: 0.78-149.71). CONCLUSIONS: Direct and indirect comparisons did not find a difference in seizure freedom between the various AEDs, probably because of the small number of patients included. LEV and LTG appears better tolerated than CR-CBZ and LEV seems associated with more AEs than LTG. Further studies are required to provide robust evidence on efficacy and tolerability of AEDs for treating poststroke epilepsy.

Why do people search Wikipedia for information on multiple sclerosis?

BACKGROUND: Wikipedia is a frequently-accessed online source of health-related information. In this study we evaluated the number of views of the Italian Wikipedia articles related to multiple sclerosis (MS) and its treatment. METHODS: Using Pageviews Analysis we assessed the total views, and mean monthly and daily views of the Italian Wikipedia articles on MS and its treatments from 1 January 2015 to 31 October 2017. We compared the views of the article on MS with those for Alzheimer´s disease, epilepsy, migraine and stroke, and adjusted results for crude disease prevalence. RESULTS: The total views of the Italian Wikipedia article on MS was 929,983 (mean monthly views: 33,214; mean daily views: 1089). The adjusted views for the Italian Wikipedia article on MS were higher than those for the other neurological disorders. The normalized views for the MS article were 16, 7, 145 and 11 times higher than those of the articles on Alzheimer's disease, epilepsy, migraine and stroke, respectively. Peaks were temporally related to famous people with MS talking about their disease in talk shows on television or to news on novel treatments for MS. CONCLUSION: Wikipedia searches do not reliably reflect its actual epidemiology. Celebrities with MS acting as testimonials might effectively increase public knowledge on MS.

Transcranial magnetic stimulation studies in complex regional pain syndrome type I: A review.

The sensory and motor cortical representation corresponding to the affected limb is altered in patients with complex regional pain syndrome (CRPS). Transcranial magnetic stimulation (TMS) represents a useful non-invasive approach for studying cortical physiology. If delivered repetitively, TMS can also modulate cortical excitability and induce long-lasting neuroplastic changes. In this review, we performed a systematic search of all studies using TMS to explore cortical excitability/plasticity and repetitive TMS (rTMS) for the treatment of CRPS. Literature searches were conducted using PubMed and EMBASE. We identified 8 articles matching the inclusion criteria. One hundred fourteen patients (76 females and 38 males) were included in these studies. Most of them have applied TMS in order to physiologically characterize CRPS type I. Changes in motor cortex excitability and brain mapping have been reported in CRPS-I patients. Sensory and motor hyperexcitability are in the most studies bilateral and likely involve corresponding regions within the central nervous system rather than the entire hemisphere. Conversely, sensorimotor integration and plasticity were found to be normal in CRPS-I. TMS examinations also revealed that the nature of motor dysfunction in CRPS-I patients differs from that observed in patients with functional movement disorders, limb immobilization, or idiopathic dystonia. TMS studies may thus lead to the implementation of correct rehabilitation strategies in CRPS-I patients. Two studies have begun to therapeutically use rTMS. This non-invasive brain stimulation technique could have therapeutic utility in CRPS, but further well-designed studies are needed to corroborate initial findings.

A critical appraisal of randomized controlled trials on intravenous phenytoin in convulsive status epilepticus.

Since the 1970s, intravenous (IV) phenytoin (PHT) has traditionally been used as second-stage treatment for convulsive status epilepticus (SE) after failure of benzodiazepines. The aim of this review was to critically assess the evidence supporting the use of IV PHT as treatment of convulsive SE in patients of any age. In particular, we critically appraised the results of randomized controlled trials (RCTs) evaluating IV PHT as treatment of convulsive SE. A systematic search of the literature was carried out to identify RCTs evaluating IV PHT as treatment of convulsive SE in patients of any age. Eight RCTs (544 patients allocated to IV PHT) were included. The included studies differed in almost every single characteristic considered. Six RCTs (472 patients) used IV PHT without demonstrating refractoriness of SE to benzodiazepines. Only two RCTs (72 patients) used IV PHT as second-line treatment for benzodiazepine-resistant convulsive SE. Overall, most evidence from RCTs supports the use of IV PHT immediately after IV diazepam, even if seizures have not recurred. The recommendation derived from RCTs supporting the use of IV PHT as second-line treatment in benzodiazepine-resistant convulsive SE is weak. This is emblematic of the lack of robust evidence from large RCTs to inform clinical practice on how to treat SE after failure of first-line drugs. IV PHT given immediately after first-line benzodiazepines could prolong their short antiepileptic effect and prevent seizure recurrence.

Low-frequency rTMS of the unaffected hemisphere in stroke patients: A systematic review.

The aim of this review was to summarize the evidence for the effectiveness of low-frequency (LF) repetitive transcranial magnetic stimulation (rTMS) over the unaffected hemisphere in promoting functional recovery after stroke. We performed a systematic search of the studies using LF-rTMS over the contralesional hemisphere in stroke patients and reviewed the 67 identified articles. The studies have been gathered together according to the time interval that had elapsed between the stroke onset and the beginning of the rTMS treatment. Inhibitory rTMS of the contralesional hemisphere can induce beneficial effects on stroke patients with motor impairment, spasticity, aphasia, hemispatial neglect and dysphagia, but the therapeutic clinical significance is unclear. We observed considerable heterogeneity across studies in the stimulation protocols. The use of different patient populations, regardless of lesion site and stroke aetiology, different stimulation parameters and outcome measures means that the studies are not readily comparable, and estimating real effectiveness or reproducibility is very difficult. It seems that careful experimental design is needed and it should consider patient selection aspects, rTMS parameters and clinical assessment tools. Consecutive sessions of rTMS, as well as the combination with conventional rehabilitation therapy, may increase the magnitude and duration of the beneficial effects. In an increasing number of studies, the patients have been enrolled early after stroke. The prolonged follow-up in these patients suggests that the effects of contralesional LF-rTMS can be long-lasting. However, physiological evidence indicating increased synaptic plasticity, and thus, a more favourable outcome, in the early enrolled patients, is still lacking. Carefully designed clinical trials designed are required to address this question. LF rTMS over unaffected hemisphere may have therapeutic utility, but the evidence is still preliminary and the findings need to be confirmed in further randomized controlled trials.

rTMS of the prefrontal cortex has analgesic effects on neuropathic pain in subjects with spinal cord injury.

STUDY DESIGN: Repetitive transcranial magnetic stimulation study. OBJECTIVES: The analgesic effects of repetitive transcranial magnetic stimulation (rTMS) in chronic pain have been the focus of several studies. In particular, rTMS of the premotor cortex/dorsolateral prefrontal cortex (PMC/DLPFC) changes pain perception in healthy subjects and has analgesic effects in acute postoperative pain, as well as in fibromyalgia patients. However, its effect on neuropathic pain in patients with traumatic spinal cord injury (SCI) has not been assessed. SETTING: Merano (Italy) and Salzburg (Austria). METHODS: In this study, we performed PMC/DLPFC rTMS in subjects with SCI and neuropathic pain. Twelve subjects with chronic cervical or thoracic SCI were randomized to receive 1250 pulses at 10 Hz rTMS (n=6) or sham rTMS (n=6) treatment for 10 sessions over 2 weeks. The visual analog scale, the sensory and affective pain rating indices of the McGill Pain Questionnaire (MPQ), the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale were used to assed pain and mood at baseline (T0), 1 day after the first week of treatment (T1), 1 day (T2), 1 week (T3) and 1 month (T4) after the last intervention. RESULTS: Subjects who received active rTMS had a statistically significant reduction in pain symptoms in comparison with their baseline pain, whereas sham rTMS participants had a non-significant change in daily pain from their baseline pain. CONCLUSION: The findings of this preliminary study in a small patient sample suggest that rTMS of the PMC/DLPFC may be effective in relieving neuropathic pain in SCI patients.

The contribution of neurophysiology in the diagnosis and management of cervical spondylotic myelopathy: a review.

STUDY DESIGN: Topical review of the literature. OBJECTIVE: The objective of this review article was to assess indications and usefulness of various neurophysiological techniques in diagnosis and management of cervical spondylogenic myelopathy (CSM). METHODS: The MEDLINE, accessed by Pubmed and EMBASE electronic databases, was searched using the medical subject headings: 'compressive myelopathy', 'cervical spondylotic myelopathy (CSM)', 'cervical spondylogenic myelopathy', 'motor evoked potentials (MEPs)', 'transcranial magnetic stimulation', 'somatosensory evoked potentials (SEPs)', 'electromyography (EMG)', 'nerve conduction studies (NCS)' and 'cutaneous silent period (CSP)'. RESULTS: SEPs and MEPs recording can usefully supplement clinical examination and neuroimaging findings in assessing the spinal cord injury level and severity. Segmental cervical cord dysfunction can be revealed by an abnormal spinal N13 response, whereas the P14 potential is a reliable marker of dorsal column impairment. MEPs may also help in the differential diagnosis between spinal cord compression and neurodegenerative disorders. SEPs and MEPs are also useful in follow-up evaluation of sensory and motor function during surgical treatment and rehabilitation. EMG and NCS improve the sensitivity of cervical radiculopathy detection and may help rule out peripheral nerve problems that can cause symptoms that are similar to those of CSM. CSP also shows a high sensitivity for detecting CSM. CONCLUSION: Neuroimaging, especially magnetic resonance imaging, represents the procedure of choice for the diagnosis of CSM, but a correct interpretation of morphological findings can be achieved only if they are correlated with functional data. The studies reported in this review highlight the crucial role of the electrophysiological studies in diagnosis and management of CSM.

Assessment of corticospinal excitability after traumatic spinal cord injury using MEP recruitment curves: a preliminary TMS study.

STUDY DESIGN: Transcranial magnetic stimulation study. OBJECTIVES: To further investigate the corticospinal excitability changes after spinal cord injury (SCI), as assessed by means of transcranial magnetic stimulation (TMS). SETTING: Merano (Italy) and Salzburg (Austria). METHODS: We studied resting motor threshold (RMT), motor evoked potential (MEP) amplitude and recruitment curve in five subjects with good recovery after traumatic incomplete cervical SCI. RESULTS: RMT did not differ significantly between patients and controls, whereas the slope of MEP recruitment curve was significantly increased in the patients. CONCLUSION: This abnormal finding may represent an adaptive response after SCI. The impaired ability of the motor cortex to generate proper voluntary movement may be compensated by increasing spinal excitability. The easily performed measurement of MEP recruitment curve may provide a useful additional tool to improve the assessment and monitoring of motor cortical function in subjects with SCI. Increasing our knowledge of the corticospinal excitability changes in the functional recovery after SCI may also support the development of effective therapeutic strategies.

rTMS modulates reciprocal inhibition in patients with traumatic spinal cord injury.

STUDY DESIGN: Randomized, double-blind, crossover, sham-controlled trial. OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) leads to a significant reduction of spasticity in subjects with spinal cord injury (SCI), but the physiological basis of this effect is still not well understood. The purpose of this study was to evaluate the disynaptic reciprocal Ia inhibition of soleus motoneurons in SCI patients. SETTING: Department of Neurology, Merano, Italy and TMS Laboratory, Paracelsus Medical University, Salzburg, Austria. METHODS: Nine subjects with incomplete cervical or thoracic SCI received 5 days of daily sessions of real or sham rTMS applied over the contralateral M1. We compared the reciprocal inhibition, the Modified Ashworth Scale and the Spinal Cord Injury Assessment Tool for Spasticity at baseline, after the last session and 1 week later in the real rTMS and sham stimulation groups. RESULTS: We found that real rTMS significantly reduced lower limb spasticity and restored the impaired excitability in the disynaptic reciprocal inhibitory pathway. CONCLUSIONS: In a small proof-of-concept study, rTMS strengthened descending projections between the motor cortex and inhibitory spinal interneuronal circuits. This reversed a defect in reciprocal inhibition after SCI, and reduced leg spasticity.