205. Neurological Manifestations of Systemic Lupus Erythematosus: A Comprehensive Review

Article type: Literature Review
Article title: Neurological Manifestations of Systemic Lupus Erythematosus: A Comprehensive Review

Journal: Cureus
Year: 2025
Authors: Maleesha Jayasinghe, Fatemeh Rashidi, Ahmed Farid Gadelmawla, Jamir Pitton Rissardo, Masoumeh Rashidi, Christopher C. Elendu, Ana Leticia Fornari Caprara, Ibrahim Khalil, Khalil I. Hmedat, Mohamed Atef, Hania Moharam, Omesh Prathiraja
E-mail: jamirrissardo@gmail.com

ABSTRACT
Neurological involvement in systemic lupus erythematosus (SLE) poses significant challenges, impacting patient morbidity, mortality, and quality of life. This narrative review provides an update on the pathogenesis, clinical presentation, diagnosis, and management of neurological SLE. The multifaceted pathophysiology involves immune-mediated and vascular mechanisms such as autoantibodies, neuroinflammation, complement dysregulation, and genetic factors. Neuropsychiatric SLE (NPSLE) manifests in a variety of ways, including cognitive dysfunction, mood disorders, psychosis, cerebrovascular disease, demyelinating syndromes, and neuropathies. Diagnosing neurological SLE is complicated by nonspecific and fluctuating symptoms, requiring comprehensive neurological examination, neuroimaging, autoantibody profiling, and cerebrospinal fluid analysis. Current management strategies include corticosteroids, immunosuppressive agents, and emerging biologics targeting specific immune pathways. Managing neuropsychiatric symptoms, seizures, and neuropathic pain remains a complex aspect of treatment. This review highlights the importance of early recognition and tailored management approaches to improve patient outcomes in neurological SLE.
Keywords: diagnosis of npsle, lupus erythematosus, neuropsychiatric systemic lupus erythematosus (npsle), sle, systemic lupus erythematosus disease.

Full text available at:

DOI

Citation
Jayasinghe M, Rashidi F, Gadelmawla AF, et al. Neurological Manifestations of Systemic Lupus Erythematosus: A Comprehensive Review. Cureus 2025;17: e79569.
Table 1. Immune-mediated mechanisms in neurological SLE. SLE: systemic lupus erythematosus, aPL: antiphospholipid, NPSLE: neuropsychiatric systemic lupus erythematosus, CNS: central nervous system, MAP-2: microtubule-associated protein 2, AECA: anti-endothelial-cell antibody, β2-GPI: beta-2-glycoprotein I, anti-RP Ab: anti-ribosomal P protein antibodies, aPL Ab: antiphospholipid antibodies, anti-MAP-2 Ab: anti-microtubule-associated protein 2 antibodies, anti-GAPDH Ab: anti-glyceraldehyde-3-phosphate dehydrogenase antibodies, BBB: blood-brain barrier.

Table 2. Diagnostic tests for neurological SLE. SLE: systemic lupus erythematosus, CNS: central nervous system, MRI: magnetic resonance imaging, CT: computed tomography, PET: positron emission tomography, CSF: cerebrospinal fluid, WM: white matter, SPECT: single-photon emission computed tomography, apL: antiphospholipid, NMO: neuromyelitis optica, NPSLE: neuropsychiatric systemic lupus erythematosus, MS: multiple sclerosis.

Table 3. Management of neuropsychiatric manifestations in SLE. SLE: systemic lupus erythematosus, DNA: deoxyribonucleic acid, IV: intravenous, CNS: central nervous system, NPSLE: neuropsychiatric systemic lupus erythematosus, IL-2: interleukin-2, GI: gastrointestinal, TPE: therapeutic plasma exchange, IVIG: intravenous immunoglobulin.

Figure 1. Pathophysiology, clinical manifestations, and treatment of NPSLE. NPSLE: neuropsychiatric systemic lupus erythematosus.

204. Accepted

203. Accepted

202. Accepted

201. Understanding Reflex Epilepsy: Triggers, Mechanisms, And Management

Article type: Literature Review
Article title: Understanding Reflex Epilepsy: Triggers, Mechanisms, And Management

Journal: IJMSDH
Year: 2025
Authors: Faiyyaz Ur Rehman, Jamir Pitton Rissardo, Nigar Hashmi, Han Gul, And Ana Letícia Fornari Caprara
E-mail: jamirrissardo@gmail.com

ABSTRACT
Reflex epilepsy, a distinctive subset of epileptic disorders, is characterized by seizures reliably triggered by specific stimuli or activities. This comprehensive literature review synthesizes current knowledge and recent advancements in understanding reflex epilepsy, shedding light on its diverse triggers, clinical manifestations, and underlying neurophysiological mechanisms. The review explores the vast array of triggers, encompassing visual stimuli, specific movements, cognitive processes, and sensory inputs, revealing the intricate interplay between external stimuli and epileptic events. Significant clinical heterogeneity is observed in reflex epilepsy, with manifestations ranging from focal motor seizures to alterations in consciousness. Advances in neuroimaging and electroencephalography have contributed valuable insights into the neurophysiological basis of reflex epilepsy, emphasizing cortical hyperexcitability and abnormalities in sensory and cognitive processing. Genetic and molecular studies have uncovered potential markers associated with reflex epilepsy, offering a glimpse into its hereditary aspects and paving the way for future diagnostic and therapeutic strategies. The literature underscores the psychosocial impact of reflex epilepsy on the quality of life of affected individuals, prompting the need for holistic, patient-centered care approaches.
Keywords: reflex epilepsy, triggers, seizure, musicogenic epilepsy, reflex, photosensitivity.

Full text available at:

DOI

Citation
Rehman FU, Rissardo JP, Hashmi N, Gul H, Caprara ALF. Understanding Reflex Epilepsy: Triggers, Mechanisms, And Management. IJMSDH 2025;11:01-19.
Figure 1. Prevalence of Different Types of Reflex Epilepsy.

200. Exploring the Neurological Manifestations of Leprosy: Clinical Insights and Implications

Article type: Literature Review
Article title: Exploring the Neurological Manifestations of Leprosy: Clinical Insights and Implications

Journal: Cureus
Year: 2025

Authors: Masoumeh Rashidi, Jamir Pitton Rissardo, Vishnu V. Byroju, Ana Leticia Fornari Caprara, Fatemeh Rashidi, Omesh Prathiraja, Hania Moharam, Christopher C. Elendu, Mallak Bahar, Maleesha Jayasinghe
E-mail: jamirrissardo@gmail.com

ABSTRACT
Leprosy is one of the neglected tropical diseases, and its elimination remains a public health problem globally. This manuscript comprehensively explores the neurological manifestations of leprosy, offering clinical insights and implications for the diagnosis, management, and understanding of this disease. Beginning with a review of historical context, etiology, and epidemiology, we delve into the pathophysiology of leprosy neuropathy, highlighting mechanisms of nerve damage and immune response. Peripheral nerve involvement, including sensory and motor deficits, nerve enlargement, and deformities, are discussed in detail, along with the challenges in diagnosis and management. Psychological and social implications of neurological deficits in leprosy are addressed, emphasizing the importance of holistic care and support. Emerging trends in neuroimaging and molecular diagnostics offer promising avenues for improved diagnosis and therapeutic interventions. Novel therapeutic strategies are identified to enhance treatment efficacy and prevent disability in leprosy neuropathy by targeting immunomodulatory pathways, antibacterial agents, and a personalized medicine approach.

Keywords: cutaneous manifestations of leprosy, hansen's disease, leprosy, leprosy complications, leprosy transmission, leprosy treatment, manifestations of leprosy, mycobacterium leprae.

Full text available at:

DOI

Citation
Rashidi M, Pitton Rissardo J, Byroju V V, et al. Exploring the Neurological Manifestations of Leprosy: Clinical Insights and Implications. Cureus 2025;17: e77799.
Figure 1. Transmission and neural invasion of Mycobacterium leprae (M. leprae). Aerosol transmission is the most accepted route, although vectors and environmental factors are still being studied. Once they enter the bloodstream, M. leprae replicate in macrophages and reach the central nervous system, where they replicate in Schwann cells. Many animals, such as armadillos and monkeys, are considered reservoirs.

Figure 2. Th1 and Th2 responses in leprosy. Antigen-presenting cells activate Th1 cells, resulting in macrophage activation and granuloma formation. This triggers a tuberculoid form of leprosy, which is less severe. When the Th2 pathway is activated, macrophage activation is limited, and disseminated disease develops, termed lepromatous leprosy.

Table 1. Receptors and molecules related with leprosy neuropathy.

Table 2. Studies on the prevalence of leprosy neuropathic pain.

Table 3. Studies using steroids in leprosy neuropathy.

199. Drug-Induced Myoclonus: A Systematic Review

Article type: Literature Review
Article title: Drug-Induced Myoclonus: A Systematic Review

Journal: Medicina
Year: 2025
Authors: Jamir Pitton Rissardo, Ana Letícia Fornari Caprara, Nidhi Bhal, Rishikulya Repudi, Lea Zlatin, and Ian M. Walker
E-mail: jamirrissardo@gmail.com

ABSTRACT
Background and Objectives: Myoclonus is already associated with a wide variety of drugs and systemic conditions. As new components are discovered, more drugs are suspected of causing this disabling abnormal involuntary movement. This systematic review aims to assess the medications associated with drug-induced myoclonus (DIM). Materials and Methods: Two reviewers assessed the PubMed database using the search term “myoclonus”, without language restriction, for articles published between 1955 and 2024. The medications found were divided into classes and sub-classes, and the subclasses were graded according to their level of evidence. Results: From 12,097 results, 1115 were found to be DIM. The subclasses of medications with level A evidence were intravenous anesthetics (etomidate), cephalosporins (ceftazidime, cefepime), fluoroquinolones (ciprofloxacin), selective serotonin reuptake inhibitors (citalopram, escitalopram, paroxetine, sertraline), tricyclic antidepressant (amitriptyline), glutamate antagonist (amantadine), atypical antipsychotics (clozapine, quetiapine), antiseizure medications (carbamazepine, oxcarbazepine, phenytoin, gabapentin, pregabalin, valproate), pure opioid agonist (fentanyl, morphine), bismuth salts, and mood stabilizers (lithium). The single medication with the highest number of reports was etomidate. Drug-induced asterixis is associated with a specific list of medications. The neurotransmitters likely involved in DIM are serotonin, dopamine, gamma-aminobutyric acid (GABA), and glutamate. Conclusions: DIM may be reversible with management that can include drug discontinuation, dose adjustment, and the prescription of a medication used to treat idiopathic myoclonus. Based on the main clinical constellation of symptoms and pathophysiological mechanisms found in this study, DIM can be categorized into three types: type 1 (serotonin syndrome), type 2 (non-serotonin syndrome), and type 3 (unknown).
Keywords: myoclonus; neurotoxicity; encephalopathy; drug-induced myoclonus; adverse effect; myoclonus/chemically induced; antidepressant-induced myoclonus; opioid-induced myoclonus; anti-seizure medication-induced myoclonus; antibiotic-induced myoclonus

Full text available at:

DOI

Citation
Rissardo JP, Fornari Caprara AL, Bhal N, Repudi R, Zlatin L, Walker IM. Drug-Induced Myoclonus: A Systematic Review. Medicina 2025;61(1):131.

Abstract Figure. Drug-induced myoclonus (DIM). Abbreviations: ASM, antiseizure medications; CBZ, carbamazepine; GABA, gamma-aminobutyric acid; GBP, gabapentin; IV, intravenous; OXC, oxcarbazepine; PGB, pregabalin; PHT, phenytoin; SSRIs, selective serotonin reuptake inhibitors; TCA, tricyclic antidepressants; VPT, valproate.

Figure 1. PRISMA flowchart of the screening process.

Figure 2. Classification of drug-induced myoclonus based on possible pathophysiological mechanisms.

Figure 3. Algorithm of management of drug-induced myoclonus.

Table 1. Drug-induced myoclonus and level of evidence.

Table 2. Proposed mechanisms for drug-induced myoclonus.

Table 3. Proposed classification for drug-induced myoclonus.

Table S1. Articles of Myoclonus Associated with Drugs in PubMed.

Table S2. Anesthetic-Induced Myoclonus.

Table S3. Antibiotic-Induced Myoclonus.

Table S4. Antidepressant-Induced Myoclonus.

Table S5. Antipsychotic-Induced Myoclonus.

Table S6. Antiseizure Medication-Induced Myoclonus.

Table S7. Opioid-Induced Myoclonus.

Table S8. Drug-Induced Asterixis.

198. Accepted

197. Galantamine-memantine combination in the treatment of Parkinson’s disease dementia

Article type: Literature Review

Article title: Galantamine-Memantine Combination in the Treatment of Parkinson’s Disease Dementia

Journal: Brain Science
Year: 2024

Authors: Emma D. Frost, Swanny X. Shi, Vishnu V. Byroju, Jamir Pitton Rissardo, Jack Donlon, Nicholas Vigilante, Briana P. Murray, Ian M. Walker, Andrew McGarry, Thomas N. Ferraro, Khalid A. Hanafy, Valentina Echeverria, Ludmil Mitrev, Mitchel A. Kling, Balaji Krishnaiah, David B. Lovejoy, Shafiqur Rahman, Trevor W. Stone, and Maju Mathew Koola
E-mail: jamirrissardo@gmail.com

ABSTRACT
Parkinson’s disease (PD) is a progressive neurodegenerative disorder that affects over 1% of population over age 60. It is defined by motor and nonmotor symptoms including a spectrum of cognitive impairments known as Parkinson’s disease dementia (PDD). Currently, the only US Food and Drug Administration-approved treatment for PDD is rivastigmine, which inhibits acetylcholinesterase and butyrylcholinesterase increasing the level of acetylcholine in the brain. Due to its limited efficacy and side effect profile, rivastigmine is often not prescribed, leaving patients with no treatment options. PD has several derangements in neurotransmitter pathways (dopaminergic neurons in the nigrostriatal pathway, kynurenine pathway (KP), acetylcholine, α7 nicotinic receptor, and N-methyl-D-aspartate (NMDA) receptors) and rivastigmine is only partially effective as it only targets one pathway. Kynurenic acid (KYNA), a metabolite of tryptophan metabolism, affects the pathophysiology of PDD in multiple ways. Both galantamine (α7 nicotinic receptor) and memantine (antagonist of the NMDA subtype of the glutamate receptor) are KYNA modulators. When used in combination, they target multiple pathways. While randomized controlled trials (RCTs) with each drug alone for PD have failed, the combination of galantamine and memantine has demonstrated a synergistic effect on cognitive enhancement in animal models. It has therapeutic potential that has not been adequately assessed, warranting future randomized controlled trials. In this review, we summarize the KYNA-centric model for PD pathophysiology and discuss how this treatment combination is promising in improving cognitive function in patients with PDD through its action on KYNA.

Keywords: cognition; drug combination; galantamine; kynurenic acid; memantine; N-acetylcysteine; neuropharmacology; Parkinson’s disease dementia; Parkinson’s disease treatment

Full text available at:
https://www.mdpi.com/2076-3425/14/12/1163

DOI
https://doi.org/10.3390/brainsci14121163

Citation
Frost ED, Shi SX, Byroju VV, Rissardo JP, Donlon J, Vigilante N, et al. Galantamine-memantine combination in the treatment of Parkinson’s disease dementia. Brain Sci 2024;14:1163.

Figure 1. Kynurenine pathway. An abbreviated depiction of the kynurenine pathway showing the major steps.

Figure 2. Overview of the kynurenine pathway in the brain and its effects. Depiction of the differential expression of the KP in cells of the central nervous system. Astrocytes lack the full complement of KP enzymes, hence KP activation in astrocytes terminates in the production of neuroprotective KYNA. However, as microglia fully express KP enzymes, KP activation in microglia can result in the production of neurotoxic metabolites 3-HK and QUIN. KP = Kynurenine Pathway; TRP = Tryptophan; KYNA = Kynurenic Acid; IDO = Indoleamine 2,3-dioxygenase; TDO = Tryptophan-2,3-dioxygenase; QUIN = Quinolinic Acid; 3-HAA = 3 Hydroxyanthranilic Acid; 3-HK = 3-hydroxykynurenine; KMO = Kynurenin-3-monooxygenase; KYN = Kynurenine.

Figure 3. Kynurenine pathway-centric pathophysiology model. Depiction of some of the receptors, pathways, and processes affected by increased levels of major kynurenine pathway metabolites KYN, KYNA, 3-HK, and QUIN after pathway activation. AhR = aryl hydrocarbon receptor; α7nAChR = Alpha7 nicotinic receptor; BCL-2 = B-cell Lymphoma 2; GABA = γ-aminobutyric acid; KYN = Kynurenine; KYNA = Kynurenic Acid; NMDA = N-methyl-D-aspartate; QUIN = Quinolinic Acid; 3-HK = 3-hydroxykynurenine. ↑, increased process; ↓, decreased process.

Figure 4. Magic bullet versus shotgun approach. The magic bullet approach has long been thought to be the answer to treating complex medical conditions. Pharmaceutical companies hoped that they would be able to develop a single drug to treat many conditions. However, this has failed countless times. We argue that the shotgun approach is more effective. Using multiple drugs (shotgun approach) to target multiple pathways implicated in a disease is likely to a more effective treatment approach.

Table 1. Meta-analyses of randomized controlled trials in schizophrenia: potential medications in Parkinson’s disease (PD).

196. Rasmussen Encephalitis: Clinical Features, Pathophysiology, and Management Strategies—A Comprehensive Literature Review

Article type: Literature Review

Article title: Rasmussen Encephalitis: Clinical Features, Pathophysiology, and Management Strategies—A Comprehensive Literature Review

Journal: Medicina
Year: 2024
Authors: Ana Leticia Fornari Caprara, Jamir Pitton Rissardo, Eric P. Nagele
E-mail: jamirrissardo@gmail.com

ABSTRACT
Rasmussen encephalitis (RE) is a rare and progressive form of chronic encephalitis that typically affects one hemisphere of the brain and primarily occurs in pediatric individuals. The current study aims to narratively review the literature about RE, including historical information, pathophysiology, and management of this condition. RE often occurs in individuals with normal development, and it is estimated that only a few new cases are identified each year in epilepsy centers. Approximately 10% of cases also occur in adolescents and adults. The hallmark feature of RE is drug-resistant focal seizures that can manifest as epilepsia partialis continua. Also, patients with RE usually develop motor and cognitive impairment throughout the years. Neuroimaging studies show progressive damage to the affected hemisphere, while histopathological examination reveals T-cell-dominated encephalitis with activated microglial cells and reactive astrogliosis. The current therapy guidelines suggest cerebral hemispherotomy is the most recommended treatment for seizures in RE, although significant neurological dysfunction can occur. Another option is pharmacological management with antiseizure medications and immunomodulatory agents. No significant progress has been made in understanding the pathophysiology of this condition in the last decades, especially regarding genetics. Notably, RE diagnosis still depends on the criteria established by Bien et al., and the accuracy can be limited and include genetically different individuals, leading to unexpected responses to management.

Keywords: rasmussen encephalitis; rasmussen syndrome; encephalitis; epilepsy; hypometabolism; epilepsia partialis continua; refractory epilepsy; cerebral hemiatrophy

Citation
Fornari Caprara AL, Rissardo JP, Nagele EP. Rasmussen Encephalitis: Clinical Features, Pathophysiology, and Management Strategies—A Comprehensive Literature Review. Medicina 2024; 60:1858.
Figure 1. The natural history of Rasmussen’s encephalitis.

Figure 2. Schematic diagram of the proposed mechanisms for the drugs related to Rasmussen’s encephalitis management. 1—Inhibition of lymphocyte T proliferation (tacrolimus, mycophenolate mofetil, and azathioprine). 2—Diapedesis blockage (natalizumab). 3—Pro-inflammatory cytokines blockage (adalimumab, anakinra, and infliximab). 4—Antibody blockage/ clearance (intravenous immunoglobulin, plasmapheresis, and adsorption). 5—Inhibition of lymphocyte B proliferation (rituximab). 6—Inhibition of T and B lymphocytes (alemtuzumab, mitoxantrone, cyclophosphamide). 7—Unknown etiology (ganciclovir). 8—Broad-spectrum anti-inflammatory action (corticosteroids).

Figure 3. Management of Rasmussen’s encephalitis. First, surgery eligibility should be assessed. Second, medical treatment can be used independent of the indication of the surgical procedure. The first-line therapies are corticosteroids ± intravenous immunoglobulin (IVIg) ± plasmapheresis/immunoadsorption. Second-line therapies are related to targeting lymphocytes, pro-inflammatory cytokines, and other mechanisms. The data is scarce in providing specific definitions for most second-line therapies in RE.

Table 1. Histological classification proposed by Robitaille et al. (1991)

Table 2. Neuroimaging stages of Rasmussen’s encephalitis proposed by Bien et al. (2005)



Table 3. Clinical criteria for Rasmussen encephalitis, adapted from Bien et al. (2005)

Table 4. Critical analysis of cases described by Olson et al. (2013)

Table 5. Medical treatment of Rasmussen’s encephalitis.

Table 6. Seizure outcomes in children with Rasmussen’s encephalitis undergoing resective or hemispheric epilepsy surgery.

Table 7. Cognitive outcome after hemispherectomy in patients with RE.

Table 8. Differential diagnosis of RE and explorations, adapted from Bien et al. (2005)

Table 9. Neuroimaging of some cerebral hemi-atrophy causes.
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