A Male Patient Presents With Isolated Abducens Nerve Palsy: An Atypical Presentation of Ocular Myasthenia Gravis.

Myasthenia gravis is an autoimmune disease of the neuromuscular junction caused by autoantibodies directed against the acetylcholine receptors. It presents with skeletal muscle weakness, often initially presenting with ocular symptoms such as ptosis and diplopia. When myasthenia gravis is isolated to only ocular symptoms, it is referred to as ocular myasthenia gravis (OMG). Here, we present an atypical initial presentation of OMG in a 68-year-old male patient presenting with isolated abducens nerve palsy at the initial onset. With this case report, we highlight the importance of a thorough history and clinical assessment necessary for a timely diagnosis of OMG in patients who present with isolated abducens nerve palsy.

Acetyl-cholinesterase-inhibitors reconsidered. A narrative review of post-marketing studies on Alzheimer's disease.

The real efficacy of Acetyl-cholinesterase-inhibitors (AChEI) has been questioned. In this narrative review we evaluated their effect on cognitive decline, measured by Mini Mental State Examination (MMSE), and on total mortality rates in patients with Alzheimer's disease (AD) recruited into post-marketing open/non-randomized/retrospective studies. In AD patients treated with AChEI, the mean MMSE loss ranged from 0.2 to 1.37 points/years, compared with 1.07-3.4 points/years in non-treated patients. Six studies also reported data about survival; a reduction in total mortality relative risk between 27% and 42% was observed, over a period of 2-8 years. The type of studies and the use of MMSE to assess cognitive decline, may have introduced several biases. However, the clinical effects of AChEI seem to be of the same order of magnitude as the drugs currently used in most common chronic disorders, as regards progression of the disease and total mortality. In the absence of long-term randomized trials on "standard" unselected AD outpatients, open/retrospective studies and health databases represent the best available evidence on the possible effect of AChEI in the real-word setting. Our data support the clinical benefit of AChEI in older patients affected by AD.

Successful use of neostigmine for resistant gastroparesis following distal gastrectomy: A case report.

INTRODUCTION AND IMPORTANCE: Although short acting acetyl cholinesterase inhibitors are used in colonic or small bowel pseudo-obstruction, their use in post-surgical gastroparesis is not clear. We demonstrate the successful use of neostigmine in a patient with resistant gastroparesis following distal gastrectomy. CASE PRESENTATION: A 73-year-old male presented with features of gastric outflow obstruction 3 weeks following a distal gastrectomy. Prior to 3 weeks, he underwent an uneventful open distal gastrectomy for an incidentally detected low grade gastrointestinal stromal tumour (GIST) of the gastric antrum. An omega-loop isoperistaltic, 2-layer, posterior, retrocolic gastrojenunostomy was performed with a jejuno-jejunostomy. Abdominal ultrasonography was negative for intra-abdominal collections. Gastrograffin study and endoscopy ruled out an obstruction. A trial of prokinetics was unsuccessful with persistent nasogastric tube drain. Intravenous neostigmine was commenced with immediate symptomatic relief, reduction of abdominal distension and bowel evacuation without any cardiac adverse effects. At 6 months follow up, the patient was tolerating normal diet with no recurrence of symptoms. CLINICAL DISCUSSION: The management of post-surgical gastroparesis is challenging. Although various prokinetics are described for gastric motility disorders, the studies among post-gastrectomy patients with gastroparesis are limited. In our patient, the successful administration of neostigmine avoided the morbidity due to revision surgery. CONCLUSION: The use of neostigmine infusion was safe and effective for post-surgical gastroparesis after distal gastrectomy in our patient. To date, there are no trials investigating the place of neostigmine for resistant gastroparesis after gastric surgery and future studies are warranted prior to routine use in clinical practice.

The Latest Advances in the Diagnosis and Treatment of Dementia.

Dementia is a debilitating neurological condition that is characterized by persistent cognitive decline. It is a global health challenge, with a rapidly increasing prevalence due to an increasing aging population. Although definitive diagnosis of various conditions of dementia is only possible by autopsy, clinical diagnosis can be performed by a specialist. The diagnostic process has evolved with recent breakthroughs in diagnostic tools, such as advanced imaging techniques and biomarkers. These tools facilitate early and accurate identification of the condition. Early diagnosis is vital, as it enables timely interventions to improve the quality of life for affected individuals. Treatment strategies for dementia encompass both pharmacological and non-pharmacological approaches. Non-pharmacological treatments include cognitive training and lifestyle modifications. Among pharmacological treatments, acetyl-cholinesterase inhibitors including donepezil, rivastigmine, and galantamine can be used in various doses based on the severity of the disease. Apart from these, N-methyl-D-aspartate receptor antagonists such as memantine can also be used. Furthermore, personalized treatments have also gained significant attention in dementia treatment. Interdisciplinary care, involving healthcare professionals, social workers, and support networks, is crucial for comprehensive and holistic dementia management.

6-Methyluracil derivatives as acetylcholinesterase inhibitors for treatment of Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is the major age-related progressive neurodegenerative disorder. The brain of AD patients suffers from loss of cholinergic neurons and decreased number of synapses [1]. AD is caused by an imbalance between Aß production and clearance, resulting in increased amount of Aß in various forms [2]. Reduction of Aß production and increasing clearance of Aß pathogenic forms are key targets in the development of potential therapeutic agents for AD treatment. Unfortunately, only nosotropic approaches for treatment of AD are currently effective in humans. These approaches mainly focus on the inhibition of brain acetyl-cholinesterase (AChE) to increase lifetime of cerebral acetylcholine [3]. It is important to emphasize that AChE itself promotes the formation of Aß fibrils in vitro and Aß plaques in the cerebral cortex of transgenic mouse models of AD [4]. This property of AChE results from interaction between Aß and the peripheral anionic site of the enzyme (PAS) [5]. Dual binding site inhibitors of both catalytic active site (CAS) and PAS can simultaneously improve cognition and slow down the rate of Aß-induced neural degeneration. Unfortunately, the assortment of AChE PAS ligands is still extremely limited. OBJECTIVE: To study putative advantages of AChE non-charged PAS inhibitors based on 6-methyluracil derivatives for the treatment of Alzheimer's disease. METHODS: In vitro studies. Concentration of drug producing 50% of AChE/BuChE activity inhibition (IC50) was measured using the method of Ellman et al. [6]. Toxicological experiments were performed using IP injection of the different compounds in mice. LD50, dose (in mg/kg) causing lethal effects in 50% of animals was taken as a criterion of toxicity [7]. The ability of compound to block in vitro AChE-induced Aß1-40 aggregation was studied using a thioflavin T (ThT) fluorescent probe [8].In vivo biological assays. For in vivo blood-brain barrier permeation assay brains were removed 30 min after IP injection of LD50 dose of tested compound injection. The inhibitory potency was measured using the method of Ellman.Scopolamine and transgenic models of AD were used to evaluate the influence of compound 35 on spatial memory performance.Water solution of scopolamine was injected to mice (ip) 20 minutes before starting memory test during 14 days [9]. Mice were assigned to 7 groups, including 4 groups receiving injection (ip) of compound in different dosages, donepezil-treated mice (donepezil is conventionally used to treat Alzheimer's disease), positive and negative control groups. Double transgenic (APP/PS1) mice expressing a chimeric mouse/human amyloid precursor protein and a mutant of human presenilin-1 [10] were assigned to 4 groups, including transgenic animals injected (ip) with compound 35 or donepezil solution, positive (transgenes injected with water) and negative (wild-type mice) controls.To evaluate spatial memory performance, mice were trained on a reward alternation task using a conventional T-maze [11]. The criterion for a mouse having learned the rewarded alternation task was 3 consecutive days of at least 5 correct responses out of the 6 free trials.For ß-amyloid peptide load was evaluated quantitatively as a number and summary area of Thioflavine S fluorescent spots in cerebral cortex and hippocampal images using Image J program. Statistical analyses were performed using the Mann-Whitney test. RESULTS: We evaluated the acute toxicity of the most active compounds. The most potent AChE inhibitor compound 35 (IC50 (AChE) = 5 ± 0.5 nM) exhibited the lowest LD50 values (51 mg/kg) and inhibited brain AChE by more than 71 ± 1%. Compound 35 at 10 nM, exhibited a significant (35 ± 9%) inhibitory activity toward human AChE-induced Aß aggregation.Scopolamine injection induced significant decrease in correct choice percentage in T-maze, as well as decrease in percentage of mice reaching criterion for learning the task by day 14. This memory deficit was relieved to some extent either by compound 35 (5 mg/kg) or donepezil (reference compound) treatment (0.75 mg/kg). Interestingly, higher doses of compound 35 (10 and 15 mg/kg) produced less therapeutic effect on spatial memory deficit.Group of APP/PS1 mice showed 3 times lower percentage of reaching behavioral criterion and lower percentage of correct choice in T-maze alternation task comparing to WT mice, whereas compound 35 (5 mg/kg) or Donepezil treatment effectively improved these parameters in APP/PS1 mice.Compound 35 treatment (5 mg/kg) during 14 days significantly reduced percentage of summary area and number of ß-amyloid peptide (ßAP) deposits visualized in sections of cerebral cortex, dentate gyrus, and hippocampal CA3 area in APP/PS1 mice. The most prominent reduction of ßAP load by compound 35 treatment was found in CA3 area and cerebral cortex. Meanwhile, Donepezil treatment (1 mg/kg) during 14 days significantly reduced ßAP load in cerebral cortex but not in dentate gyrus and CA3 area. CONCLUSIONS: Experiments showed that the most potent AChE inhibitor compound 35 (6-methyluracil derivative) permeated the blood-brain barrier, improved working memory in the APP/PS1 transgenic mice and significantly reduced the number and area of Aß plaques in the brain. Thus, compound 35 is a promising candidate as a bi-functional inhibitor of AChE for treatment of AD.

RBC acetyl cholinesterase: A poor man's early diagnostic biomarker for familial alzheimer's and Parkinson's disease dementia.

OBJECTIVE: Analysis of red blood cell acetyl cholinesterase (AChE) in a familial Alzheimer's diseases (AD) Parkinson's disease dementia (PDD) and their first generation. SETTING: General hospital, Mahad district, Raigad. PATIENTS AND METHODS: Clinically diagnosed patients of AD and PDD and their asymptomatic relatives. Their blood was collected in EDTA tube and transferred to laboratory at Mumbai. RESULT: Median red blood cell (RBC) cholinesterase levels amongst PDD, their first generation asymptomatic relatives, familial AD, asymptomatic relatives of AD, healthy controls, farmers exposed to pesticides (positive control) and other neurological condition without dementia (hypertension with TIA 1, sub-dural hematoma 2, hypothyroid 1, non-familial unilateral parkinsonism without dementia 3, writers cramps 2, hyponitremia 1 and cerebral palsy with non-fluent aphasia 1). Median values of RBC AChE were 19086.78 U/L, 15666.05 U/L, 9013.11 U/L, 7806.19 U/L, 14334.57 U/L, 9785.05 U/L and 13162.60 U/L, respectively. As compared to controls, RBC AChE levels were statistically significant among PDD (P = 0.004) and significantly lowered among familial AD patients (P = 0.010), relatives of patients (P = 0.010). INTERPRETATIONS: Below the normal RBC AChE level is a potential biomarker in asymptomatic relatives of familial AD patients. RBC AChE is raised than normal level in patients suffering from PDD, where AChE inhibitors are helpful. However, RBC AChE level below the normal where AChE inhibitor may not be effective.

Treatment of Visual Hallucinations in Schizophrenia by Acetylcholinesterase Inhibitors: a case report.

Schizophrenia and various neurological disorders have some signs and symptoms. Visual hallucinations are one of such disorders. The related studies in some diseases for example Parkinson Disease and Lewy Body Dementia indicate that Acetylcholine (Ach) plays a significant role in neuropsychiatric manifestation and its association with visual hallucination; therefore, visual hallucinations occur due to the depletion of Ach. Drug therapies such as Cholinesterase inhibitors (ChEIs) for increasing Ach level may be beneficial in treating visual hallucination. AchEI's have been used in the treatment of visual hallucinations in Dementia and Parkinson's Disease. We thought that a similar Ach depletion may cause visual hallucinations in patients with schizophrenia and may provide a target for drug treatment. We had a patient with schizophrenia whose psychotic symptoms responded to the treatment plan, but her visual hallucination did not. However, the patient's visual hallucination successfully responded to Rivastigmine (AchEI).This case illustrates the use of an AchEI in the treatment of refractory visual hallucinations in a patient with schizophrenia.