241. Minimal Hepatic Encephalopathy: A Narrative Review

Article type: Literature Review
Article title: Minimal Hepatic Encephalopathy: A Narrative Review

Journal: Cureus
Year: 2026
Authors: Jamir Pitton Rissardo, Fatemeh Rashidi, Hania Moharam, Ibrahim Khalil, Meryem Bahar, Masoumeh Rashidi, Basem Ahmed, Saleh Salem, Ana Leticia Fornari Caprara, Abhishek A. Chouthai, Ahmed M. Kedwany, Hagar H. Sayed, Omesh Prathiraja, Maleesha Jayasinghe
E-mail: jamirrissardo@gmail.com

ABSTRACT
Minimal hepatic encephalopathy (MHE) is primarily a cognitive disorder linked to chronic liver disease that often remains underdiagnosed due to the subtlety of its clinical manifestations. These symptoms are frequently overlooked or dismissed as inconsequential in clinical practice, leading to many undiagnosed cases. The standard neurological examination is usually normal in individuals with MHE. Regular and systematic screening for MHE is essential for early detection, which can improve cognitive outcomes and prevent progression to a more serious and debilitating condition known as overt hepatic encephalopathy. The pathophysiology of MHE is very complex and multifactorial, involving several interacting mechanisms. Mainly, hyperammonemia, systemic inflammation, gut-derived neurotoxins, oxidative stress, and mitochondrial dysfunction are at its root. Any of these factors may interfere with the normal functioning of neurotransmitters, giving rise to the typical subtle cognitive impairments that are hallmarks of MHE. The Animal Naming Test and EncephalApp-Stroop test are practical, rapid, and easily administered tools for screening for minimal hepatic encephalopathy in outpatient and bedside settings. Emerging diagnostic technologies, including advanced neuroimaging techniques and novel biomarkers, have also been investigated and show promise for improving the early detection and diagnosis of MHE.
Keywords: chronic liver diseases, driving impairment, electroencephalography, hepatic encephalopathy, minimal hepatic encephalopathy, neurocognitive testing, neuropsychological testing, psychometric tests, quality of life

Full text available at:

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Citation
Rissardo JP, Rashidi F, Moharam H, Khalil I, Bahar M, Rashidi M, Ahmed B, Salem S, Fornari Caprara AL, Chouthai AA, Kedwany AM, Sayed HH, Prathiraja O, Jayasinghe M. Minimal Hepatic Encephalopathy: A Narrative Review. Cureus 18(8): e113978. doi:10.7759/cureus.113978.
Figure 1. Grades of hepatic encephalopathy.
Figure 2. Role of ammonia in the pathophysiology of hepatic encephalopathy.
Figure 3. The algorithm for arriving at the diagnostically appropriate diagnosis of minimal hepatic encephalopathy.
Figure 4. Proposed clinical algorithm for the diagnosis of minimal hepatic encephalopathy.
Table 1. Diagnostic methods for the detection of MHE. ANT: Animal Naming Test, CFF: critical flicker frequency testing, CHE: covert hepatic encephalopathy, CRT: Continuous Response Time test, EEG: electroencephalography, HRQOL: health-related quality of life, ICT: Inhibitory Control Test, MHE: minimal hepatic encephalopathy, PHES: Psychometric Hepatic Encephalopathy Score, RBANS: Repeatable Battery for the Assessment of Neuropsychological Status, SIP: Sickness Impact Profile, 3-NT: 3-nitrotyrosine.
Table 2. Precipitating factors diagnosis and management. BRTO: Balloon-Occluded Transvenous Retrograde TIPS: transjugular intrahepatic portosystemic shunt, SPSS: spontaneous portosystemic shunt, BRTO: balloon-occluded retrograde transvenous obliteration, CARTO: coil-assisted retrograde transvenous obliteration, PARTO: plug-assisted retrograde transvenous obliteration, HE: hepatic encephalopathy, IV: intravenous, BMI: body mass index, DEXA: dual-energy X-ray absorptiometry, GI: gastrointestinal, PPI: proton pump inhibitor.Obliteration, CARTO: Coil-Assisted Retrograde Transvenous Obliteration, PARTO: Plug-assisted BRTO.
Table 3. Published studies on the management of minimal hepatic encephalopathy. BCAA: branched-chain amino acids, BDT: block design test, CFF: critical flicker frequency, CEP: cognitive evoked potentials, DST: digit symbol test, EEG: electroencephalogram, FOS: fructooligosaccharide, HRQOL: health-related quality of life, ICT: inhibitory control test, LTT: line tracing test, MHE: minimal hepatic encephalopathy, NCT-A: number connection test-A, NCT-B: number connection test-B, NfL: Neurofilament light, OHE: overt hepatic encephalopathy, PHES: psychometric hepatic encephalopathy score, SDT: serial dotting test, SIBO: small intestinal bacterial overgrowth.

240. Accepted.

239. Accepted

Abstracts - 2026

 2026


AAPM Pain Connect - Salt Lake City

Spinal Cord Stimulation in Parkinson’s Disease: Beyond Motor Control—A Path to Pain Relief

Beyond Motor Control: Deep Brain Stimulation Significantly Reduces Pain in Parkinson’s Disease

MDS PAS 2026 - Houston







World Parkinson Congress - Phoenix





ACNS Annual Meeting - New Orleans

Successful Surgical Treatment of Radiation-Induced Epilepsy Using sEEG: A Case Report

EEG-Guided Anesthesia in Cardiothoracic Surgery: Does BIS Improve Neurological Outcomes?

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Smartphone Videos for Seizure Diagnosis: High Specificity Compared to cEEG

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Rowan Research Day - Stratford

Cerebrospinal Fluid and Serum Manganese Levels in Parkinson’s Disease: A Method‑Stratified Meta‑analysis

Effects of Subthalamic Nucleus Deep Brain Stimulation on Depressive Symptoms in Patients with Parkinson’s Disease: A Meta‑Analysis

Efficacy and Safety of Droxidopa for Neurogenic Orthostatic Hypotension: A Systematic Review and Meta‑analysis

Efficacy and Safety of Levetiracetam for Essential Tremor: A Systematic Review and Meta‑Analysis

Focal Status Epilepticus in a Patient with Responsive Neurostimulation: A Rare Complication and Management Insights

Irritability and Related Behavioral Adverse Events Associated With Levetiracetam: A Meta‑Analysis and Meta‑Regression of Randomized Trials

Missense Mutations in the SNCA Gene: Molecular Mechanisms and Clinical Implications

Prevalence and Clinical Correlates of Restless Legs Syndrome in Neuromyelitis Optica Spectrum Disorder: A Systematic Review and Meta‑analysis

Trends and Disparities in Mortality Involving Epilepsy and Aspiration Pneumonia Among Older Adults in the United States, 1999–2020

Wearable and Technology‑Assisted Gait and Balance Interventions in Parkinson’s Disease: A Systematic Review and Meta‑Analysis

AAN - Chicago
























Comparing the Efficacy and Safety of Endovascular Therapy versus Best Medical Treatment in Patients with Distal Medium Vessel Occlusion: A Systematic Review and Meta-Analysis





AAIC - London, UK

Harnessing Gamma: Randomized Placebo-controlled Evidence For 40 Hz Sensory Stimulation In Alzheimer’S Disease

Repetitive Transcranial Magnetic Stimulation In Severe Alzheimer Disease: A Meta-analytic Evaluation Of Cognitive Outcomes

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P2P - Phoenix


ATMRD - Washington, D.C.

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Retinal Structural Changes in Huntington Disease: An OCT‑Based Meta‑analysis

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Efficacy and Safety of Curcumin Supplementation in Parkinson’s Disease: A Meta‑Analysis of Randomized Controlled Trials

MDS International Congress - Seoul, Korea

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Subthalamic Deep Brain Stimulation Produces Consistent Improvements in Sleep Quality and Daytime Sleepiness in Parkinson’s Disease: A Systematic Review and Meta-analysis

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Effects of Modafinil on Motor and Non‑Motor Outcomes in Parkinson’s Disease: A Meta‑Analysis of Randomized, Placebo‑Controlled Trials

Efficacy and Safety of Inhaled and Sublingual Apomorphine for On-Demand Treatment of OFF Episodes in Parkinson’s Disease: A Meta‑Analysis of Randomized Placebo‑Controlled Trials

Efficacy and Adverse Events of Tetrabenazine, Deutetrabenazine, and Valbenazine in Huntington’s Disease

Clinical Impact of Nicotine in Parkinson’s Disease: Evidence from Randomized Controlled Studies

Motor and Quality‑of‑Life Outcomes After MR‑Guided Focused Ultrasound Subthalamotomy for Parkinson’s Disease: A Meta‑analysis

Ketogenic Diet and Motor Outcomes in Parkinson’s Disease: A Meta-analysis of Randomized Trials

Efficacy and Safety of Ecopipam for Tourette Syndrome: A Meta‑analysis of Controlled Trials

A Meta-analysis of Tonic Motor Activation (TOMAC) Therapy for Restless Legs Syndrome

Efficacy and Safety of Mesdopetam (IRL790) for Levodopa‑Induced Dyskinesia in Parkinson’s Disease: A Meta‑analysis of Randomized Controlled Trials

Efficacy of Vitamin C for Restless Legs Syndrome: A Systematic Review and Meta‑analysis of Randomized Controlled Trials

Antidepressants in Huntington’s Disease: A Meta‑Analysis of Mood and Motor Outcomes with Placebo-controlled Trials

Risk of Deep Venous Thrombosis in Patients With Parkinson’s Disease: A Meta‑Analysis of Observational Studies

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Escitalopram for Depression and Motor Symptoms in Parkinson’s Disease: A Systematic Review and Meta‑analysis

ISFTD - Philadelphia, PA

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C9orf72-Associated Parkinsonism: Defining a Multisystem Neurodegenerative Spectrum

ANA - San Diego, CA

Deferiprone in Parkinson’s Disease: Motor, Imaging, and Safety Outcomes Across Randomized Trials

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Abstracts - 2025

 2025


AANS - Boston


AAN - San Diego












MDS International Congress - Hawaii, USA










CNS - LA










AES - Atlanta

Abstracts - 2023

2023

238. Accepted

237. Accepted

236. Accepted

235. Neurodegeneration in Parkinson’s Disease: The Role of Environmental Toxins

Article type: Literature Review
Article title: Neurodegeneration in Parkinson’s Disease: The Role of Environmental Toxins

Journal: Journal of Central Nervous System Disease
Year: 2026
Authors: Jamir Pitton Rissardo, Megan Katz, Vishnu Vardhan Byroju, Ana Letícia Fornari Caprara, and Ian M. Walker

ABSTRACT
Parkinson’s disease (PD) is a rapidly growing global health challenge, with prevalence projected to reach 13–14 million cases by 2040. While aging and improved diagnostic awareness partly explain this trend, mounting evidence implicates environmental factors as critical contributors. This review synthesizes current literature on exposures such as pesticides, solvents, heavy metals, air pollutants, and infectious agents, emphasizing their mechanistic links to neurodegeneration. These factors interact with genetic susceptibility and aging, supporting the “multiple-hit” hypothesis, which posits that PD arises from cumulative insults rather than a single cause. Mitochondrial dysfunction, oxidative stress, neuroinflammation, and impaired protein clearance emerge as convergent pathways underlying dopaminergic vulnerability. Recent findings highlight viral infections—particularly SARS-CoV-2—as potential triggers or amplifiers of PD pathogenesis, raising concerns about long-term neurological sequelae following pandemics. Beyond individual toxins, the exposome concept underscores the lifelong interplay of physical, chemical, and social exposures in shaping disease risk. Climate-related changes, including increased air pollution and wildfire frequency, further compound these risks, suggesting a systemic dimension to PD etiology. Understanding these complex interactions is essential for developing preventive strategies, refining experimental models, and informing public health policies aimed at mitigating environmental contributions to neurodegeneration. This multifactorial perspective offers a foundation for future research targeting modifiable risk factors and resilience mechanisms in PD.
Keywords: Parkinson’s disease, neurodegeneration, environmental toxins, pesticides, air pollution, heavy metals, solvents, multiple-hithypothesis, SARS-CoV-2, exposome 

Full text available at:

DOI

Citation
Pitton Rissardo J, Katz M, Byroju VV, Fornari Caprara AL, Walker IM. Neurodegeneration in Parkinson’s Disease: The Role of Environmental Toxins. Journal of Central Nervous System Disease. 2026;18. doi:10.1177/11795735261461554.
Figure 1. Likelihood of diagnosing Parkinson’s Disease (PD). The probability of a PD diagnosis increases as the cumulative burden of risk factors rises. Key contributors include aging, chronic inflammation, and exposure to environmental toxins and pollutants. These factors interact with genetic susceptibility—particularly high-penetrance mutations—to elevate disease risk. The synergistic effect of these elements underscores the multifactorial nature of PD pathogenesis.
Figure 2. Role of exposome in Parkinson’s Disease. Exposure to environmental factors through an individual’s life-time plays a role in pathogenesis of Parkinson’s disease. (A) Heavy metals (Iron, Zinc, Mercury, Lead, Copper) exposure through paint, tools and drinking water. (B) Air pollution and environmental toxins containing PM2.5, NO2, O3 and other particles. (C) Pesticide and fungicide exposure to 2,4-dichlorodiphenyldichloroethylene, Rotenone, diquat, paraquat and others. (D) Helicobacter pylori infection and other gut microbiomes exert influence. (E) Exercise and physical activity. (F) Exposure to nicotine, intravenous drugs and toxins such as MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). (G) Diet and understanding of macro and micronutrients.
Table 1. Environmental and Biological Risk Factors Associated With Parkinson’s Disease.
Table 2. Toxic Models of Parkinson’s Disease.