Alzheimer’s disease (AD) is a major type of dementia and neurodegenerative disease, characterized by memory loss and cognitive decline. Over decades, significant efforts have been dedicated to finding its cause, pathogenic mechanisms, biomarkers for early detection, and clinical trials for its treatment. Earlier approved drugs mainly ameliorated the symptoms of AD, until recent years when two drugs targeting amyloid-beta (Aβ) protein were approved to slow down the progression of the disease. This review article encompasses the history of drug development in treating AD and clinical trials that failed and succeeded. Clinicaltrials.org website was systematically searched and screened for randomized controlled trials with results posted in the past 10 years. Among the 3,388 AD clinical trials, 211 interventional studies registered under AD have met eligibility. This review includes the interventional targets for drug discovery such as Aβ, tau, neurotransmitter receptors, neuroinflammation, multi-target studies, repurposing pharmacological agents, non-pharmacological interventions, and clinical therapy development for the neuropsychiatric symptoms of dementia. Current clinical trials are ongoing and no results are available as of yet. With the vast choices of drug targets that have been investigated, this review aims to present some insights into future AD drug design and trials and contribute to our ongoing efforts to find the cure.

Neurological disorders including neurodegenerative disorders continue to pose significant therapeutic challenges. Triterpenoids, a diverse group of natural compounds found abundantly in plants, possess promising neuroprotective properties. This review aims to explore the potential of triterpenoids in mitigating neurodegeneration through various mechanisms, including antioxidant, anti-inflammatory, and anti-apoptotic activities. The neuroprotective potential of some notable triterpenoids, such as asiatic acid, asiaticoside, madecassoside, bacoside A, bacopaside I, ganoderic acids, and lucidenic acids are discussed in terms of their ability to modulate key pathways implicated in neurological disorders. Additionally, the potential therapeutic applications of triterpenoids in Alzheimer’s disease, Parkinson’s disease, cerebral ischemia, spinal cord injury, and epilepsy are examined. Furthermore, the review also underlines the challenges for the development of triterpenoids as neuroprotective agents, including the need for further preclinical and clinical studies to elucidate their efficacy and safety for translation into clinical practice.

New onset refractory status epilepticus (NORSE) is an etiologically heterogeneous condition that is associated with high morbidity and mortality. NORSE is often refractory to medical management prompting a workup for epilepsy surgery. Because NORSE remains etiologically elusive in most cases, surgical evaluations are challenging, especially when the epileptogenic zone (EZ) is not easy to lateralize as can be seen in frontal lobe seizures. Lateralizing a frontal lobe EZ may be challenging due to bilateral synchrony from commissural connections through the corpus callosum and low spatiotemporal resolution of the scalp electroencephalography (EEG). We report a pediatric patient with NORSE presenting with focal impaired awareness seizures clustering into super refractory status epilepticus (SRSE). She required surgical intervention for the treatment of her seizures after failing therapeutic doses of antiseizure medications, anesthetic drips, immunomodulation with methylprednisolone, intravenous immunoglobulin and anakinra, and the ketogenic diet. Despite her semiology being focal, the seizures were not well lateralized on scalp EEG and during phase 2 stereo-EEG (sEEG). Anterior magnetic resonance-guided laser interstitial thermal therapy corpus callosotomy (MRgLITT CC) was performed in a multistage surgical approach to successfully lateralize the EZ with a left-lateralized ictal pattern seen after reimplantation of sEEG electrodes. Our case suggests that minimally invasive MRgLITT CC can be successfully used to lateralize an EZ in frontal lobe epilepsy and that epilepsy surgery should be considered in patients with NORSE with SRSE. We also demonstrate that laser interstitial thermal therapy (LITT), while not always resulting in seizure freedom, can sufficiently disrupt a network to abort status epilepticus and lead to seizure improvements.

Epileptic seizures are prevalent in people with brain vascular abnormalities like arteriovenous malformations (AVMs) and cavernous malformations, greatly affecting their quality of life. The connection between intracranial vascular abnormalities and epilepsy is still under debate. Therefore, investigating epilepsy in individuals with AVMs is a crucial and current research area. This review presents a comprehensive examination of recent developments in epilepsy among individuals with brain AVMs. The authors conducted a detailed analysis of the natural progression, epidemiology, diagnostic methods, therapeutic approaches, and post-treatment outcomes for individuals with epilepsy associated with AVMs.

Major depressive disorder (MDD) is a common mental disorder associated with significant suffering and disability. Recent evidence has highlighted the role of the gut-brain axis in the pathogenesis of MDD. Enteric glial cells are a structurally and functionally diverse population that plays a key role in regulating enteric nervous function and maintaining intestinal mucosal integrity. These cells may be implicated in the origin of several digestive and extra-digestive disorders, known as enteric neuro-gliopathies (ENG). This paper reviews the evidence that MDD may also belong to the category of ENG. Animal models suggest that environmental adversity can lead to enteric glial dysfunction and depressive-like behaviors. Conditions that are highly comorbid with MDD, both intestinal and extra-intestinal, have been linked to enteric glial alterations. Peripheral blood markers linked to glial integrity and function are altered in patients with MDD, and certain treatments for MDD may have beneficial effects on enteric glial functioning. Though much of this evidence is indirect and provisional, it suggests that MDD may belong to the group of ENG. Further investigation of enteric glial functioning in MDD may yield valuable insights into the pathophysiology and treatment of this disorder.

Brain metastasis is the most prevalent neurologic problem of systemic cancer and it can increase the mortality rate in patients with cancer. It occurs more in patients with lung cancer, breast cancer, and melanoma. There are several molecular mechanisms in cancer cell progression, invasion, and location in new places during brain metastasis. Significant interactions between cancer cells, the brain microenvironment, and the blood-brain barrier (BBB) play a major role in brain metastasis. This study will focus on molecular mechanisms that contribute to cancer metastasis into the brain and finding new treatments with molecular research. Treatment strategies in patients with brain metastasis include surgical resection, radiotherapy, and chemotherapy; however, the penetration of chemotherapy drugs beyond the BBB is limited. Studying molecular, cellular, and physical mechanisms in brain metastasis helps to improve new strategies in drug delivery across the BBB. There are significant impacts of ion channels in brain metastasis and cancer treatment failure. Targeting molecular mechanisms and ion channels in brain metastasis led to increasing the better response in these patients. In this way, nano-drugs have caused a revolution in effective targeting and drug delivery in cancer treatment. This review describes the advances to facilitate the penetration of drugs in the BBB by using nano-drugs especially those that are targeting ion channels.