Introduction. Migraine is a common, debilitating primary headache. Memantine is a non-competitive N-methyl D-aspartate (NMDA) antagonist that lowers neuronal excitability that could prevent migraine attacks. This study aimed to determine the efficacy and safety of memantine in patients with episodic migraine attacks using a systematic review and meta-analysis.

Methods. We searched CENTRAL, MEDLINE, Scopus, Cochrane, LILACS, ClinicalTrials.gov, HERDIN and Google Scholar for relevant studies until July 31, 2020. Prespecified screening and eligibility criteria for inclusion were applied. Included studies underwent methodological quality assessment. Study design, patient characteristics, interventions given, and relevant outcomes were extracted and synthesized.

Results. This review included five relevant articles - two randomized controlled trials (RCT) and three non randomized studies (one retrospective records review and survey, two prospective open-label single-arm trials). There were 109 patients included in the RCTs and 197 patients reported in the non-randomized studies. Pooled data from the two RCTs showed that memantine at 10 mg/day significantly decreased the monthly number of migraine days at 12 weeks compared to placebo with a mean difference of -1.58 [95% confidence interval (CI) -1.84, -1.32]. Non-randomized studies also showed a decrease in migraine days per month with memantine (5 to 20 mg/day) after 12 weeks [95% CI]: -9.1 [-11, -7.23], -7.2 [-8.85, -5.55], and -4.9 [-6.29, -3.51]. Adverse drug events (ADE) did not differ significantly between patients treated with memantine compared to placebo.

Conclusion. Memantine may be effective and well-tolerated as prophylaxis for episodic migraine.

BACKGROUND: Alzheimer's dementia is the most common dementia. However, recently, choline alfoscerate is prescribed for treating Alzheimer's dementia, although it is not a treatment for this disease. PURPOSE: To analyze the prescription patterns of choline alfoscerate as a dementia treatment for patients with Alzheimer's disease and to analyze, as well as the factors affecting choline alfoscerate prescription. METHOD: The 2016 HIRA-NPS data was used in this study. The code of Alzheimer's dementia is F00 in the ICD-10 disease classification code. We analyzed the demographic, clinical, and regional characteristics associated with donepezil, rivastigmine, galantamine, memantine, and choline alfoscerate prescriptions. All statistical and data analyse were conducted by SAS 9.4 and Excel. RESULTS: For patients with Alzheimer's disease, choline alfoscerate was the second most prescribed after donepezil. Analysis results showed that choline alfoscerate was more likely to be prescribed to men than to women, and more likely to be prescribed by local health centers than by medical institutions. Moreover, choline alfoscerate was highly likely to be prescribed at neurosurgical departments, among medical departments. CONCLUSION: This study confirmed that choline alfoscerate was prescribed considerably for patients with Alzheimer's dementia. Further studies valuating its clinical validity should be performed to clarify whether choline alfoscerate prescription is appropriate for treating Alzheimer's dementia.
Alzheimer Disease ; Choline ; Classification ; Dementia ; Female ; Galantamine ; Glycerylphosphorylcholine ; Humans ; International Classification of Diseases ; Male ; Memantine ; Methods ; Prescriptions ; Rivastigmine

Parkinson's disease is one of the most common neurodegenerative disorders world widely. Although curable therapies are practically not available yet, symptomatic managements using anti-Parkinson medications have shown to be quite effective to improve patients' quality of life. The discovery of dopaminergic deficits in Parkinson's disease in 1960s have brought about the human clinical trials of levodopa, which opened an “Era of Dopamine” in treatment history of the Parkinson's disease. Levodopa still remains gold standard. Dopamine agonists have proved their efficacies and delayed the development of long-term complications of levodopa use. Inhibitors of respective enzyme monoamine oxidase-B and catechol-O-methyltransferase, anticholinergics, and amantadine strengthen the therapeutic effects via either monotherapy or adjunctive way. Strategy of continuous dopaminergic stimulation and disease modification are weighing in current advances. This article is providing evidence-based review of pharmacological treatment of Parkinson's disease from early to advanced stages as well as management its unavoidable adverse reactions.
Amantadine ; Catechol O-Methyltransferase ; Cholinergic Antagonists ; Dopamine Agonists ; Drug Therapy ; Humans ; Levodopa ; Neurodegenerative Diseases ; Parkinson Disease ; Quality of Life ; Therapeutic Uses

Memantine is a non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist clinically approved for moderate-to-severe Alzheimer's disease (AD) to improve cognitive functions. There is no report about the proteomic alterations induced by memantine in AD mouse model yet. In this study, we investigated the protein profiles in the hippocampus and the cerebral cortex of AD-related transgenic mouse model (3×Tg-AD) treated with memantine. Mice (8-month) were treated with memantine (5 mg/kg/bid) for 4 months followed by behavioral and molecular evaluation. Using step-down passive avoidance (SDA) test, novel object recognition (NOR) test and Morris water maze (MWM) test, it was observed that memantine significantly improved learning and memory retention in 3xTg-AD mice. By using quantitative proteomic analysis, 3301 and 3140 proteins in the hippocampus and the cerebral cortex respectively were identified to be associated with AD abnormalities. In the hippocampus, memantine significantly altered the expression levels of 233 proteins, among which PCNT, ATAXIN2, TNIK, and NOL3 were up-regulated, and FLNA, MARK 2 and BRAF were down-regulated. In the cerebral cortex, memantine significantly altered the expression levels of 342 proteins, among which PCNT, PMPCB, CRK, and MBP were up-regulated, and DNM2, BRAF, TAGLN 2 and FRY1 were down-regulated. Further analysis with bioinformatics showed that memantine modulated biological pathways associated with cytoskeleton and ErbB signaling in the hippocampus, and modulated biological pathways associated with axon guidance, ribosome, cytoskeleton, calcium and MAPK signaling in the cerebral cortex. Our data indicate that memantine induces higher levels of proteomic alterations in the cerebral cortex than in the hippocampus, suggesting memantine affects various brain regions in different manners. Our study provides a novel view on the complexity of protein responses induced by memantine in the brain of AD.
Alzheimer Disease ; Animals ; Axons ; Brain ; Calcium ; Cerebral Cortex ; Cognition ; Computational Biology ; Cytoskeleton ; Hippocampus ; Learning ; Memantine ; Memory ; Mice ; Mice, Transgenic ; N-Methylaspartate ; Proteome ; Ribosomes ; Water

Memantine, a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) receptor, suppresses the release of excessive levels of glutamate that may induce neuronal excitation. Here we investigated the effects of memantine on salicylate-induced tinnitus model. The expressions of the activity-regulated cytoskeleton-associated protein (ARC) and tumor necrosis factor-alpha (TNF α)genes; as well as the NMDA receptor subunit 2B (NR2B) gene and protein, were examined in the SH-SY5Y cells and the animal model. We also used gap-prepulse inhibition of the acoustic startle reflex (GPIAS) and noise burst prepulse inhibition of acoustic startle, and the auditory brainstem level (electrophysiological recordings of auditory brainstem responses, ABR) and NR2B expression level in the auditory cortex to evaluate whether memantine could reduce salicylate-mediated behavioral disturbances. NR2B was significantly upregulated in salicylate-treated cells, but downregulated after memantine treatment. Similarly, expression of the inflammatory cytokine genes TNFα and immediate-early gene ARC was significantly increased in the salicylate-treated cells, and decreased when the cells were treated with memantine. These results were confirmed by NR2B immunocytochemistry. GPIAS was attenuated to a significantly lesser extent in rats treated with a combination of salicylate and memantine than in those treated with salicylate only. The mean ABR threshold in both groups was not significant different before and 1 day after the end of treatment. Additionally, NR2B protein expression in the auditory cortex was markedly increased in the salicylate-treated group, whereas it was reduced in the memantine-treated group. These results indicate that memantine is useful for the treatment of salicylate-induced tinnitus.
Acoustics ; Animals ; Auditory Cortex ; Brain Stem ; Evoked Potentials, Auditory, Brain Stem ; Genes, Immediate-Early ; Glutamic Acid ; Immunohistochemistry ; Integrin alpha2 ; Memantine ; Models, Animal ; N-Methylaspartate ; Neurons ; Noise ; Prepulse Inhibition ; Rats ; Reflex, Startle ; Tinnitus ; Tumor Necrosis Factor-alpha

Cryptococcus neoformans is the most common microorganism found in cerebrospinal fluid (CSF) cytology and causes life-threatening infections in immunocompromised hosts. Although its cytomorphologic features in conventional smear cytology have been well described, those in liquid-based cytology have rarely been. A 73-year-old woman with diffuse large B-cell lymphoma presented with mental confusion and a spiking fever. To rule out infectious conditions, CSF examination was performed. A cytology slide that was prepared using the ThinPrep method showed numerous spherical yeast-form organisms with diameters of 4–11 μm and thick capsules. Occasional asymmetrical, narrow-based budding but no true hyphae or pseudohyphae were observed. Gomori methenamine silver staining was positive. Cryptococcosis was confirmed in blood and CSF through the cryptococcal antigen test and culture. Liquid-based cytology allows for a clean background and additional slides for ancillary testing, facilitating the detection of microorganisms in CSF specimens, particularly when the number of organisms is small.
Aged ; Capsules ; Cerebrospinal Fluid ; Cryptococcosis ; Cryptococcus neoformans ; Female ; Fever ; Humans ; Hyphae ; Immunocompromised Host ; Lymphoma, B-Cell ; Meningitis, Cryptococcal ; Methenamine ; Methods

Dementia is a clinical syndrome characterized by a cluster of symptoms and signs that manifest as difficulties in cognitive functions such as memory, psychological and psychiatric changes, and impairments in activities of daily living. As a result of worldwide trends of population aging, dementia has had a huge impact on public health in almost all countries. Disease modification therapies for dementia have not yet been developed. However, pharmacotherapy is essential in patients with dementia to combat delays in their cognitive and functional decline. In this article, we review the current pharmacotherapy for dementia. Three acetylcholinesterase inhibitors—donepezil, rivastigmine, galantamine—and memantine are the only medications that have been approved for the treatment of dementia. We present the indications, dose recommendations, side effects, and criteria for National Health Insurance coverage in Korea of these medications for dementia treatment. Although the Ministry of Food and Drug Safety in Korea has not approved any medications for managing the behavioral and psychological symptoms of dementia, some antipsychotics and antidepressants have been studied and used clinically for those purposes. Clinicians may consider vitamin E, Ginkgo biloba extract, choline alfoscerate, or omega-3 fatty acids as additional treatment options. Non-steroid anti-inflammatory drugs, estrogen hormone therapy, and statins are not generally recommended for dementia treatment. We believe that our findings will aid clinicians in the treatment of patients with cognitive decline.
Acetylcholinesterase ; Activities of Daily Living ; Aging ; Antidepressive Agents ; Antipsychotic Agents ; Cholinesterase Inhibitors ; Cognition ; Dementia ; Drug Therapy ; Estrogens ; Fatty Acids, Omega-3 ; Ginkgo biloba ; Glycerylphosphorylcholine ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Korea ; Memantine ; Memory ; National Health Programs ; Public Health ; Rivastigmine ; Vitamin E ; Vitamins

OBJECTIVE: We examined whether amantadine can prevent the development of dyskinesia. METHODS: Patients with drug-naïve Parkinson's disease (PD), younger than 70 years of age and in the early stage of PD (Hoehn and Yahr scale < 3), were recruited from April 2011 to December 2014. The exclusion criteria included the previous use of antiparkinsonian medication, the presence of dyskinesia, significant psychological disorders, and previous history of a hypersensitivity reaction. Patients were consecutively assigned to one of 3 treatment groups in an open label fashion: Group A-1, amantadine first and then levodopa when needed; Group A-2, amantadine first, dopamine agonist when needed, and then levodopa; and Group B, dopamine agonist first and then levodopa when needed. The primary endpoint was the development of dyskinesia, which was analyzed by the Kaplan-Meier survival rate. RESULTS: A total of 80 patients were enrolled: Group A-1 (n = 27), Group A-2 (n = 27), and Group B (n = 26). Twenty-four patients were excluded from the analysis due to the following: withdrawal of amantadine or dopamine agonist (n = 9), alternative diagnosis (n = 2), withdrawal of consent (n = 1), and breach in the protocol (n = 12). After exclusion, 5 of the 56 (8.93%) patients developed dyskinesia. Patients in Group A-1 and A-2 tended to develop dyskinesia less often than those in Group B (cumulative survival rates of 0.933, 0.929, and 0.700 for A-1, A-2, and B, respectively; p = 0.453). CONCLUSION: Amantadine as an initial treatment may decrease the incidence of dyskinesia in patients with drug-naïve PD.
Amantadine ; Diagnosis ; Dopamine Agonists ; Dyskinesias ; Humans ; Hypersensitivity ; Incidence ; Levodopa ; Parkinson Disease ; Survival Rate

Purpureocillium lilacinum, formerly Paecilomyces lilacinus, is a saprophytic fungus found in soil and rotting vegetation and rarely pathogenic to humans. Only 4 cases of cutaneous infection caused by Purpureocillium lilacinum have been reported in the name of Paecilomyces lilacinus. Herein, we report a case of localized cutaneous infection due to Purpureocillium lilacinum. A healthy 81-year-old immunocompetent male presented with an erythematous scaly and pustular plaque on his left dorsal hand that had begun 3 months ago. Histopathologic examination showed suppurative granulomatous inflammation with hyphae and round spores in the dermis. Periodic acid-Schiff and methenamine silver stain revealed fungal spores. Fungus culture from the biopsy specimen revealed velvety pink to white colonies after 15 day-incubation period. The slide culture stained with lactophenol-cotton blue showed typical long hyphae and flask-shaped phialides with oval conidia in chains. The result of DNA sequencing from the colony was identical to that of Purpureocillium lilacinum.
Aged, 80 and over ; Biopsy ; Dermis ; Fungi ; Hand ; Humans ; Hyphae ; Inflammation ; Male ; Methenamine ; Paecilomyces ; Sequence Analysis, DNA ; Skin* ; Soil ; Spores ; Spores, Fungal

Cryptococcosis is caused by several Cryptococcus species, including C. neoformans and C. gattii. Skin involvement is seen in 10~20% of systemic cryptococcosis. There are also rare cases of primary cutaneous cryptococcosis in which skin-penetrating trauma is the alleged mechanism of infection. A 16-year-old male presented with multiple, 0.2~0.3 cm-sized, brownish papules on the whole body for 2 weeks. He had past history of acute lymphoblastic leukemia and received bone marrow transplant 1 year ago. After leukemia had recurred 1 month ago and after chemotherapy, multiple brownish papules developed. Histopathologic examinations revealed narrow-based budding yeasts in hematoxylin and eosin, Periodic acid-Schiff, and Gomori methenamine silver stains. Also in mucicarmine stain there were pink-colored capsules around the cell walls. Finally it was diagnosed as deep fungal infection due to Cryptococcus species. In spite of administrating fluconazole, the patient expired due to respiratory failure caused by pneumonia. Herein, we report a case of Cryptococcus species infection in a bone marrow transplant patient.
Adolescent ; Bone Marrow* ; Capsules ; Cell Wall ; Coloring Agents ; Cryptococcosis ; Cryptococcus* ; Drug Therapy ; Eosine Yellowish-(YS) ; Fluconazole ; Hematoxylin ; Humans ; Leukemia ; Male ; Methenamine ; Pneumonia ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Respiratory Insufficiency ; Saccharomycetales ; Skin