Expert Review of Neurotherapeutics

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, REM 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. Hence, non-invasive 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. Amongst them external trigeminal nerve stimulation (eTNS) was first to obtain FDA approval for migraine therapy...

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 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...

Treatment of dystonia should be individualized and tailored to the specific needs of patients. Surgical treatment is an important option in medically refractory cases. Several issues regarding type of the surgical intervention, targets, and predict factors of benefit are still under debate. Areas covered: To date, several clinical trials have proven the benefit and safety of deep brain stimulation (DBS) for inherited and idiopathic isolated dystonia, whereas there is still insufficient evidence in combined and acquired dystonia...

Antipsychotics have long been the mainstay of treatment for agitation and psychosis in Alzheimer's disease. Despite their current use successive studies have shown that they only confer a modest benefit which must be balanced against their well-established serious side effects (extrapyramidal symptoms, stroke, accelerated cognitive decline and mortality). Areas covered: This review outlines the current guidance on antipsychotic usage and the evidence of their continued usage against a backdrop of emerging pharmacological treatments and an increasing emphasis on the importance of non-pharmacological interventions...

Mobility disability is one of the most widespread and impactful consequences of multiple sclerosis (MS). Disease modifying drugs (DMDs) may delay the progression of disability over time; however, there is minimal evidence supporting the efficacy of DMDs for reversing mobility disability or restoring ambulatory function in persons with MS. Areas covered: This review outlines symptomatic pharmacologic and non-pharmacologic therapeutic approaches that target mobility disability with the goal of restoring and improving walking function...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

Chronic noncancer pain has remained a challenging clinical problem. Opioid analgesics are effective, but they are known to be associated with opioid use disorder and potentially treatment-limiting side effects. Buprenorphine is a Schedule III synthetic opioid in the USA with a chemical structure similar to that of morphine but with a longer duration of action, greater potency, and other unique pharmacological attributes. Its role in treatment of chronic noncancer pain may be broader than currently thought. Areas covered: The pharmacokinetics, pharmacodynamics, clinical efficacy, and safety profile of transdermal buprenorphine in moderate chronic noncancer pain syndromes patients will be discussed...

Deep brain stimulation (DBS) of the posterior hypothalamic region (pHyr) has been shown to be efficacious for more than a half of patients suffering from trigeminal autonomic cephalalgias (TACs); nonetheless, controversies about the mechanisms of action and the actual site of stimulation have arisen in recent years. Areas covered: Firstly, a review of the most recent literature on the subject is presented, stressing the critical points that could, in the future, make a difference for optimal management of patients afflicted by these life-threating diseases...

Chronic myelomonocytic leukaemia (CMML) is a clonal hematopoietic stem cell disorder characterized by the presence of an absolute monocytosis in the peripheral blood (>1 x 109 /L) and the presence of myelodysplastic and myeloproliferative features in the bone marrow. Involvement of the central nervous system (CNS) is uncommon in CMML. Areas covered: Herein described is a case report of a CMML patient who presents with symptomatic chronic subdural collection overlying a haemorrhagic brain lesion, along with diffuse dural infiltration, after two cycles of azacytidine...

No abstract text is available yet for this article.

Primary central nervous system lymphoma (PCNSL) retains peculiar biological and clinical characteristics and a worse prognosis with respect to other comparable lymphomas. The need for high doses of chemotherapy to achieve valid drug concentrations in cerebral tissues and/or radiotherapy results in severe treatment-related toxicities, mainly neurologic, which are frequently as disabling as the disease itself. Areas covered: Several emerging combined therapies are addressed that focus on treating PCNSL. The prognosis has improved in the last years but several questions remain unanswered and the research of more effective therapies goes on...

No abstract text is available yet for this article.

Astroglia represent the main cellular homeostatic system of the central nervous system (CNS). Astrocytes are intimately involved in regulation and maintenance of neurotransmission by regulating neurotransmitters removal and turnover and by supplying neurons with neurotransmitters precursors. Astroglial cells are fundamental elements of monoaminergic transmission in the brain and in the spinal cord. Astrocytes receive monoaminergic inputs and control catabolism of monoamines through dedicated transporters and intracellular enzymatic pathways...

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that causes progressive muscle weakness and disability, eventually leading to death. Heterogeneity of disease has become a major barrier to understanding key clinical questions such as prognosis and disease spread, and has disadvantaged clinical trials in search of therapeutic intervention. Patterns of disease have been explored through recent advances in neuroimaging, elucidating structural, molecular and functional changes. Unique brain signatures have emerged that have lent a greater understanding of critical disease mechanisms, offering opportunities to improve diagnosis, guide prognosis, and establish candidate biomarkers to direct future therapeutic strategies...