Leukodystrophy Imaging: Insights for Diagnostic Dilemmas.

Leukodystrophies, a group of rare demyelinating disorders, mainly affect the CNS. Clinical presentation of different types of leukodystrophies can be nonspecific, and thus, imaging techniques like MRI can be used for a more definitive diagnosis. These diseases are characterized as cerebral lesions with characteristic demyelinating patterns which can be used as differentiating tools. In this review, we talk about these MRI study findings for each leukodystrophy, associated genetics, blood work that can help in differentiation, emerging diagnostics, and a follow-up imaging strategy. The leukodystrophies discussed in this paper include X-linked adrenoleukodystrophy, metachromatic leukodystrophy, Krabbe's disease, Pelizaeus-Merzbacher disease, Alexander's disease, Canavan disease, and Aicardi-Goutières Syndrome.

Amyotrophic Lateral Sclerosis: From Mechanisms to Current, Emerging, and Alternative Therapeutics.

Amyotrophic Lateral Sclerosis (ALS) is a severe neurodegenerative disease affecting the motor neurons. Although the etiology remains unknown, mutations in superoxide dismutase 1 have been observed in patients with familial ALS, resulting in increased calcium in the cells and leading to cell death. Additionally, studies in patients with the C9orf72 repeat expansion have shown lower age of onset, cognitive and behavioral impairments, and reduced survival. Accumulation of TDP-43 in the cytoplasm of neurons and glial cells caused by the loss of UBQLN2 has been shown to lead to mitotoxicity and proteasomal overload. Early diagnosis of ALS is necessary for the optimization of care between a patient's neurologist and interdisciplinary team members to ensure the best outcomes possible. Proper management between physical therapy, occupation therapy, and pharmaceutical medications can improve ALS symptoms, achieving the highest quality of life possible for the patient. The current therapeutic medication recommended for ALS is Riluzole, but new therapies are emerging. This paper analyzes mechanisms of injury and progression of ALS along while analyzing current, emerging, and alternative therapeutics targeting ALS.

Neurologic orphan diseases: Emerging innovations and role for genetic treatments.

Orphan diseases are rare diseases that affect less than 200000 individuals within the United States. Most orphan diseases are of neurologic and genetic origin. With the current advances in technology, more funding has been devoted to developing therapeutic agents for patients with these conditions. In our review, we highlight emerging options for patients with neurologic orphan diseases, specifically including diseases resulting in muscular deterioration, epilepsy, seizures, neurodegenerative movement disorders, inhibited cognitive development, neuron deterioration, and tumors. After extensive literature review, gene therapy offers a promising route for the treatment of neurologic orphan diseases. The use of clustered regularly interspaced palindromic repeats/Cas9 has demonstrated positive results in experiments investigating its role in several diseases. Additionally, the use of adeno-associated viral vectors has shown improvement in survival, motor function, and developmental milestones, while also demonstrating reversal of sensory ataxia and cardiomyopathy in Friedreich ataxia patients. Antisense oligonucleotides have also been used in some neurologic orphan diseases with positive outcomes. Mammalian target of rapamycin inhibitors are currently being investigated and have reduced abnormal cell growth, proliferation, and angiogenesis. Emerging innovations and the role of genetic treatments open a new window of opportunity for the treatment of neurologic orphan diseases.

Mapping the Glymphatic Pathway Using Imaging Advances.

The glymphatic system is a newly discovered waste-clearing system that is analogous to the lymphatic system in our central nervous system. Furthermore, disruption in the glymphatic system has also been associated with many neurodegenerative disorders (e.g., Alzheimer's disease), traumatic brain injury, and subarachnoid hemorrhage. Thus, understanding the function and structure of this system can play a key role in researching the progression and prognoses of these diseases. In this review article, we discuss the current ways to map the glymphatic system and address the advances being made in preclinical mapping. As mentioned, the concept of the glymphatic system is relatively new, and thus, more research needs to be conducted in order to therapeutically intervene via this system.

Mechanisms of Mitochondrial Oxidative Stress in Brain Injury: From Pathophysiology to Therapeutics.

Mitochondrial oxidative stress has been implicated in various forms of brain injury, both traumatic and non-traumatic. Due to its oxidative demand, the brain is intimately dependent on its mitochondrial functioning. However, there remains appreciable heterogeneity in the development of these injuries regarding ROS and their effect on the sequelae. These include traumatic insults such as TBIs and intracranial hemorrhaging secondary to this. In a different vein, such injuries may be attributed to other etiologies such as infection, neoplasm, or spontaneous hemorrhage (strokes, aneurysms). Clinically, the manner of treatment may also be adjusted in relation to each injury and its unique progression in the context of ROS. In the current review, then, the authors highlight the role of mitochondrial ROS in various forms of brain injury, emphasizing both the collective and unique elements of each form. Lastly, these narratives are met with the current therapeutic landscape and the role of emerging therapies in treating reactive oxygen species in brain injuries.