Role of the Glymphatic System in Alzheimer's Disease and Treatment Approaches: A Narrative Review.

Currently, there is unavailability of disease-modifying medication for Alzheimer's disease (AD), a debilitating neurological disorder. The pathogenesis of AD appears to be complex and could be influenced by the glymphatic system present in the central nervous system (CNS). Amyloid-beta (Aß) and other metabolic wastes are eliminated from the brain interstitium by the glymphatic system, which encompasses perivascular channels and astroglial cells. Dysfunction of the glymphatic system, which could occur due to decreased aquaporin 4 (AQP4) expression, aging-related alterations in the human brain, and sleep disruptions, may contribute to the pathogenesis of AD and also accelerate the development of AD by causing a buildup of harmful proteins like Aß. Promising approaches have been examined for reducing AD pathology, including non-pharmacological therapies that target glymphatic function, like exercise and sleep regulation. In addition, preclinical research has also demonstrated the therapeutic potential of pharmaceutical approaches targeted at augmenting AQP4-mediated glymphatic flow. To identify the precise processes driving glymphatic dysfunction in AD and to find new treatment targets, more research is required. Innovative diagnostic and treatment approaches for AD could be made possible by techniques such as dynamic contrast-enhanced MRI, which promises to evaluate glymphatic function in neurodegenerative diseases. Treatment options for AD and other neurodegenerative diseases may be improved by comprehending and utilizing the glymphatic system's function in preserving brain homeostasis and targeting the mechanisms involved in glymphatic functioning. This review intends to enhance the understanding of the complex link between AD and the glymphatic system and focuses on the function of AQP4 channels in promoting waste clearance and fluid exchange.

A Rare Diagnosis of Aseptic Hypertrophic Pachymeningitis: A Case of Mycobacterial Tuberculosis Origin.

Tubercular meningitis is a rare yet devastating type of extrapulmonary tuberculosis (TB) posing great diagnostic challenges due to the nonspecific clinical presentation of the patients. Here, we present a rare diagnosis of hypertrophic pachymeningitis due to Mycobacterium tuberculosis. A 36-year-old male presented with a history of headaches and giddiness for one month. Neurological examination revealed hypo-reflexive triceps and ankle reflexes. Routine blood tests and autoimmune workup were normal. Brain MRI with contrast revealed diffuse dural thickening, focal leptomeningeal enhancement in the right temporal sulci, and enhancement in both the frontal and parietal convexity and the falx cerebri and along the tentorium cerebelli. Cerebrospinal fluid (CSF) analysis revealed elevated proteins, suggestive of aseptic meningitis. Meningeal biopsy revealed a chronic ill-formed granulomatous inflammatory lesion with occasional acid-fast bacilli, consistent with tubercular pachymeningitis. The patient was administered intravenous (IV) methylprednisolone for five days, following which the symptoms subsided. He was advised tablet prednisolone on discharge, and immunomodulation with rituximab was recommended as outpatient treatment. Hypertrophic pachymeningitis is a rare diagnosis characterized by the inflammation and fibrosis of the dura matter due to a diverse etiology. Tubercular etiology must be considered when the routine laboratory tests are negative, and the diagnosis should be confirmed by meningeal biopsy. The treatment of the underlying cause and corticosteroids remain the mainstay management of hypertrophic pachymeningitis. Hence, mycobacterial tuberculosis should be considered as a possible differential diagnosis while evaluating hypertrophic pachymeningitis, especially when the routine laboratory tests and immunological workup are negative.

Dropped Head Syndrome Secondary to Danon Disease: A Case Report.

Dropped head syndrome (DHS) is characterized by neck extensor muscle weakness, which may be isolated or secondary to another neurologic diagnosis. DHS, due to lysosomal storage disorders, has not been reported in the literature. We present a 21-year-old male who had complaints of slowly worsening difficulty swallowing for the past eight years, along with difficulty keeping his head erect. His past medical history was significant for apical hypertrophic cardiomyopathy (HCM), and he had a history of sudden cardiac death in his immediate family. Clinical examination was significant only for neck extensor muscle weakness. His laboratory investigations were unremarkable, save for a significantly elevated creatine kinase (CK). Finally, whole exome sequencing identified a hemizygous stop gain variant in the lysosome-associated membrane protein 2 (LAMP-2) gene, pointing to a diagnosis of Danon disease (DD). DD is a rare, X-linked, inherited disease, due to a defect in the LAMP-2 gene that disrupts lysosomal autophagy. It is characterized by a triad of HCM, skeletal myopathy, and intellectual disability. Males typically suffer a more severe phenotype, and the cardiac disease drives its prognosis. Management involves regular cardiac monitoring, with appropriate physical therapy for myopathy and multidisciplinary treatment for intellectual disability. We suggest that DD be considered in the differential diagnosis for patients with HCM and elevated CK.

Pediatric Posterior Reversible Encephalopathy Syndrome Secondary to Post-Streptococcal Glomerulonephritis: A Case Report.

This case report presents a unique case of a 15-year-old male with post-streptococcal glomerulonephritis (PSGN) who developed posterior reversible encephalopathy syndrome (PRES). The patient presented with symptoms of fever, headache, emesis, visual disturbances, and involuntary movements of all four limbs. On examination, the patient had elevated blood pressure, decreased visual acuity of the left eye, leukocytosis, and uremia. MRI findings showed symmetrical enhancement of superficial and deep watershed areas, predominantly in the occipital and temporal regions. Treatment with antibiotics and anti-hypertensives resulted in the complete resolution of hyperintense lesions seen in brain MRI after three weeks, and the patient remained symptom-free for one month. This case highlights the rare association between PSGN and PRES and emphasizes the importance of monitoring and managing hypertension in patients with PSGN. Understanding the association between these two conditions may lead to earlier diagnosis and treatment of PRES, ultimately improving patient outcomes.

Connecting the Dots: The Interplay Between Stroke and the Gut-Brain Axis.

This article discusses the interplay between the gut-brain axis and stroke, a multifaceted neurological disorder that affects millions of people worldwide. The gut-brain axis is a bidirectional communication network linking the central nervous system (CNS) to the gastrointestinal tract (GIT), including the enteric nervous system (ENS), vagus nerve, and gut microbiota. Dysbiosis in the gut microbiota, alterations in the ENS and vagus nerve, and gut motility changes have been linked to increased inflammation and oxidative stress, which are contributing factors in the development and progression of stroke. Research on animals has shown that modifying the gut microbiota can impact the results of a stroke. Germ-free mice displayed improved neurological function and decreased infarct volumes, indicating a positive effect. Furthermore, studies in stroke patients have shown alterations in the gut microbiota composition, indicating that targeting dysbiosis could be a potential therapeutic strategy for stroke. The review suggests that targeting the gut-brain axis may represent a potential therapeutic approach to reduce the morbidity and mortality associated with stroke.

A Case of Borderline Tuberculoid Leprosy With Type One Lepra Reaction.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, which primarily affects the skin and peripheral nerves. The variants that can be identified include tuberculoid (TT), borderline tuberculoid (BT), mid-borderline (BB), borderline lepromatous (BL), and lepromatous forms (LL). Type one lepra reactions are delayed hypersensitivity reactions that are often observed in borderline variants due to an unstable immunological response. They can exacerbate skin lesions and neuritis, leading to a higher risk of disabilities and deformities. Early detection and management would play a major role in limiting morbidity. Here, we present a case of a 46-year-old male diagnosed with borderline tuberculoid leprosy on multidrug therapy who developed features suggestive of type one lepra reaction. Early recognition of this entity helps in mitigating the risk of permanent nerve damage, disability, deformity, and morbidity.

Exploring the Correlation Between Influenza A Virus (H3N2) Infections and Neurological Manifestations: A Scoping Review.

Influenza A virus (IAV), particularly the H3N2 variant, is known to cause respiratory manifestations, but it can also lead to neurological complications ranging from mild symptoms like headache and dizziness to severe conditions such as encephalitis and acute necrotizing encephalopathy (ANE). In this article, the correlation between the H3N2 variant of the IAV and neurological manifestations is discussed. Additionally, prompt recognition and treatment of influenza-associated neurological manifestations are highlighted to prevent infection-related long-term complications. This review briefly discusses various neurological complications linked to IAV infections, such as encephalitis, febrile convulsions, and acute disseminated encephalomyelitis, and the potential mechanisms involved in the development of neurological complications.

Ipsilateral Hemiparesis in a Patient With Existing Contralateral Hemiparesis: A Case Report of a Rare Presentation of Ischemic Stroke.

Supratentorial strokes causing ipsilateral hemiparesis (ILH) are rare. We report a middle-aged male with multiple atherosclerotic risk factors, who had previously suffered a right-hemispheric stroke that caused left hemiplegia. Subsequently, he presented with worsening left-sided hemiplegia, with imaging revealing a left-hemispheric stroke. Diffusion tensor tract imaging showed crossed motor tracts, with disruption of the left-sided pyramidal tract. During his stay, he developed right hemiplegia due to the expansion of the same left-hemispheric infarct. Potential mechanisms for ILH in a stroke include injury to reorganized tracts following an initial insult and congenitally uncrossed motor tracts. In our patient, after his first stroke, the left hemisphere likely assumed greater ipsilateral motor control, causing ILH after the recent stroke. Our case adds to the literature on this interesting phenomenon and provides further insight into post-stroke recovery.

Evaluation of Acute Symptomatic Seizures and Etiological Factors in a Tertiary Care Hospital From a Developing Country.

INTRODUCTION: The etiologies of acute symptomatic seizures (ASS) differ across the globe. We aimed to evaluate the etiological spectrum of acute seizures and to observe the pattern of seizure types among study participants. METHODOLOGY: We conducted this prospective study from 2016 to 18. We included all patients aged 20 years or older, presenting with ASS. We excluded those with pseudoseizures. We performed appropriate descriptive analyses to describe the demographic details, etiology of ASS, and pattern of ASS. RESULTS: One hundred and thirty-eight patients were enrolled, constituting about 0.8% of total hospital admissions. The mean age at presentation was 44.33 ± 17.73 years. The most common etiologies for ASS were cerebrovascular accidents (CVA - 32.6%), neuroinfections (26.8%), metabolic derangements (13%), alcohol withdrawal (10.9%), and intracranial tumors (4.3%). 71% of the patients presented with only a single episode of ASS. The predominant type of seizure was generalized tonic-clonic seizures, seen in 70.2% of all patients, followed by focal with the bilateral tonic-clonic type (15.9%) and focal seizures (10.1%). New-onset seizures presenting as status epilepticus were observed in 3.6%. DISCUSSION: CVA and neuroinfections were the most common causes of ASS in our study, highlighting the need for community awareness of these conditions and the need to seek rapid care. The majority of our patients had only a single episode of seizures, with generalized seizures being the most common type, followed by focal onset seizures.