Expert Review of Neurotherapeutics

Restless Legs Syndrome/Willis-Ekbom Disease (RLS/WED) is a sleep disorder characterized by an urge to move the legs, frequently associated or triggered by unpleasant sensations in the lower limbs that affects approximately 2.5% of adults. Therapy and management of RLS/WED require long term interventions, since the typical manifestation of this disorder is chronic. Areas covered: In this review, we provide an update regarding the treatment of RLS/WED with particular attention to future challenges for its management...

Reminiscence therapy (RT) is a popular psychosocial intervention widely used in dementia care. It involves discussion of past events and experiences, using tangible prompts to evoke memories or stimulate conversation. Areas covered: The aim of this review is to evaluate the effectiveness of RT for people with dementia. It includes studies from the specialized register of the Cochrane Dementia and Cognitive Improvement Group (ALOIS). Searches yielded 185 records of which 22 (n=1972) were eligible for inclusion...

Fibromyalgia (FM) is a chronic disorder whose symptoms of musculo-skeletal pain, fatigue, sleep disturbances and cognitive impairment pervade the personal, occupational and social aspects of a patient's life. Together with the antidepressants duloxetine and milnacipram, the anticonvulsant pregabalin (PGB) is one of the three drugs approved by the Food and Drug Administration (FDA) for the treatment of FM. The aim of this narrative review is to summarise the data relating to the efficacy and safety of the controlled-release formulation of PGB (PGB-CR) in patients with FM...

No abstract text is available yet for this article.

Progressive myoclonus epilepsies (PMEs) constitute a rare and heterogeneous group of genetic disorders with a distinctive triad of myoclonus, seizures, and progressive neurological deterioration. PMEs, even though rare, are arguably the severest form of epilepsies accounting for <1% of all epilepsies with age at onset varying from infancy to adulthood, depending on the disease. A majority are inherited as autosomal recessive traits, however rare types following autosomal dominant and mitochondrial inheritance are also present...

Limb Girdle Muscular Dystrophies (LGMD) encompasses a clinically heterogeneous group of rare, genetic progressive muscle disorders presenting with weakness and atrophy of predominant pelvic and shoulder muscles. The spectrum of disease severity ranges from severe childhood-onset muscular dystrophy to adult-onset dystrophy. Areas covered: The review presents an update of the clinical phenotypes and diagnostic options for LGMD including both dominant and recessive LGMD and consider their differential clinical and histopathological features...

Evaluation of people with Parkinson's disease (PD) is often complex due to heterogeneity of symptoms and disease course, including the variability of motor fluctuations and dyskinesia. Routine clinical evaluations may be incomplete, may not accurately capture important symptoms, and may not reflect day-to-day variability. While significant advances have been made in wearable ambulatory continuous objective monitoring (COM) technologies, many clinicians remain uncertain of how to incorporate them in clinical practice, including the value to clinical decision-making...

Integrated genomics has significantly advanced our understanding of medulloblastoma heterogeneity. It is now clear that it actually comprises at least four distinct molecular subgroups termed Wnt/Wingless (WNT), Sonic Hedgehog (SHH), Group 3, and Group 4 with stark clinical and biological differences. Areas covered: This paper reviews advances in the classification and risk stratification of medulloblastoma, specifically integrating subgroup with clinical and cytogenetic risk factors, with a summary of the potential to lead to more precise therapies...

Cerebrolysin is a neuropeptide preparation with neurotrophic effects and promotes recovery after brain injury. Its preclinical profile promises wide applications due to its multi-target effects. Currently, Cerebrolysin is used for treatment of cerebral ischemia and neurodegeneration. Areas covered: In stroke, earlier clinical trials with Cerebrolysin were performed mostly in mildly affected stroke populations, which usually have a favorable prognosis. Due to this selection, a floor or ceiling effect of recovery measures in the mild cases may have prevented to show a clear benefit between treatment groups...

Huntington's disease (HD) is an inherited neurodegenerative disorder for which no disease-modifying treatment is currently available. Only symptomatic treatment can be offered. Chorea is the most common motor manifestation of HD and may interfere with daily activities, reduce quality of life, and cause injury. Areas covered: Deutetrabenazine is the first deuterated drug and second drug after tetrabenazine, the classic vesicular monoamine transporter type 2 (VMAT2) inhibitor, to receive approval for the treatment of chorea associated with HD...

Primary neurological disorders are notoriously debilitating and deadly, and over the past four decades stem cell therapy has emerged as a promising treatment. Translation of stem cell therapies from the bench to the clinic requires a better understanding of delivery protocols, safety profile, and efficacy in each disease. Areas covered: In this review, benefits and risks of intracerebral stem cell transplantation are presented for consideration. Milestone discoveries in stem cell applications are reviewed to examine the efficacy and safety of intracerebral stem cell transplant therapy for disorders of the central nervous system and inform design of translatable protocols for clinically feasible stem cell-based treatments...

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder with no cure and conventional treatments limited by significant adverse effects and variable benefit. In the last decade, therapeutic development has expanded based on improved understanding of autoimmunity and financial incentives for drug development in rare disease. Clinical subtypes exist based on age, gender, thymic pathology, autoantibody profile, and other poorly defined factors, such as genetics, complicate development of specific therapies...

Peripheral neuropathy is a common symptom throughout the population, with numerous possible etiologies. The diagnosis of peripheral neuropathies (and their causes) is mainly based on clinical, electrophysiological, biological, and imaging features. Areas covered: This paper reviews the main causes of neuropathy and discusses the usefulness of nerve biopsy (NB) in such cases. Expert commentary: In most cases, NB is not mandatory in the diagnostic work-up of a peripheral neuropathy. However, NB is clearly an indication in cases of vasculitis...

Stroke is a major cause of disability and death in the United States and across the world, and the incidence and prevalence of stroke are expected to rise significantly due to an aging population. Obstructive sleep apnea, an established independent risk factor for stroke, is a highly prevalent disease that is estimated to double the risk of stroke. It remains uncertain whether non-apnea sleep disorders increase the risk of stroke. Areas covered: This paper reviews the literature describing the association between incident stroke and sleep apnea, rapid eye movement sleep behavior disorder, restless legs syndrome, periodic limb movements of sleep, insomnia, and shift work...

Progressive supranuclear palsy (PSP) is associated with microtubule-associated protein tau dysfunction. Originally thought to result in a syndrome of atypical Parkinsonism, vertical supranuclear gaze palsy, and cognitive impairment, several additional phenotypic manifestations of PSP pathology have been described over the last 20 years. Furthermore, prototypical PSP features may develop late, making early diagnosis challenging. Areas covered: An in-depth view of emerging knowledge in the field of PSP. Advances in clinicopathologic correlation, blood, cerebrospinal, and more importantly neuroimaging biomarkers are discussed in light of the 2017 PSP diagnostic criteria by the Movement Disorders Society Study Group...

Available preventive drug treatments for migraine lack complete efficacy and often have unpleasant adverse effects. Hence, their clinical utility and therapeutic adherence are limited. Noninvasive neurostimulation methods applied over various peripheral sites (forehead, mastoid, upper arm, cervical vagus nerve) have raised great interest because of their excellent efficacy/tolerance profile. Among them external trigeminal nerve stimulation (eTNS) was first to obtain FDA approval for migraine therapy. Areas covered: All clinical trials of eTNS as preventive or acute migraine treatment published in extenso or presented at congresses are reviewed...

In current migraine clinical practice, no specific diagnostic investigations are available and therefore the diagnosis is an eminently clinical process where instrumental examinations may have a part to exclude possible causes of secondary headaches. While migraine clinical phenotype has been widely characterized, migraine pathophysiology has still a gap that might be partly bridged by structural and functional neuroimaging investigations. Areas covered: This article aims to review the recent advances in functional neuroimaging, the consequent progress in the knowledge of migraine pathophysiology and their putative application and impact in the clinical setting...

Epigenetic modifications have recently been linked to neurodegenerative diseases, such as frontotemporal dementia (FTD), which represents the second most common form of dementia in adulthood after Alzheimer's disease (AD). Epigenetic regulation occurs at different cellular levels and serve as a way to alter genetic information not only in aging but also following environmental signals. Thus, epigenetics mechanisms could exert their function at early stage of the disease, especially in sporadic cases. Areas covered: Herein, the available evidence supporting the concept that epigenetic-driven changes might shed the light into the pathogenic mechanisms of FTD will be summarized, with particular regard to their influence in underlying sporadic/familiar FTD onset and/or severity, and to the possibility to open a new scenario to facilitate early diagnosis and the identification of novel therapeutic targets...

Neuroprotection and remyelination are two unmet needs in the treatment of multiple sclerosis (MS). Therapeutic potential has been identified with sexual hormones, supported in women by a decrease in MS activity during the pregnancy, in men by a greater severity of symptoms and a faster progression than in women. Areas covered: The therapeutic effect of testosterone and estrogens is reviewed. Both hormones have demonstrated an anti-inflammatory effect. Testosterone has an effect in protecting neurons in culture against glutamate-induced toxicity and oxidative stress, and stimulates myelin formation and regeneration mediated through the neural androgen receptor...

Cerebral amyloid angiopathy (CAA) is characterized by the pathologic deposition of amyloid-beta within cortical and leptomeningeal arteries, arterioles, capillaries and, in rare cases, the venules of the brain. It is often associated with the development of lobar intracerebral hemorrhages (ICHs) but may cause other neurologic symptoms or be asymptomatic. Magnetic resonance imaging characteristics, such as lobar microbleeds, support a diagnosis of CAA and assist with hemorrhage risk assessments. Immunosuppressants are used to treat rarer inflammatory forms of CAA...