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Human immunoglobulin, delivered either intravenously (IVIg) or subcutaneously, is used to treat a range of immune-mediated neurological disorders. It has a role in acute or subacute inflammatory disease control and as a maintenance therapy in chronic disease management. This review considers mechanisms of IVIg action and the evidence for IVIg in neurological conditions. We use Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) as frameworks to demonstrate an approach to IVIg use in acute and chronic dysimmune neurological conditions across two different healthcare systems: the UK and Australia. We highlight the benefits and limitations of IVIg and focus on practical considerations such as informed consent, managing risks and adverse effects, optimal dosing and monitoring response. We use these basic clinical practice principles to discuss the judicious use of an expensive and scarce blood product with international relevance.
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OBJECTIVE: To evaluate the ability of semiology alone in localising the epileptogenic zone (EZ) in people with frontal lobe epilepsy (FLE) who underwent resective surgery. METHODS: We examined data on all individuals who had FLE surgery at our centre between January 01, 2011 and December 31, 2020. Descriptions of ictal semiology were obtained from video-EEG telemetry reports and presurgical multidisciplinary meeting summaries. The putative EZ was represented by the final site of resection. We assessed how well initial and combined set-of-semiologies correlated anatomically with the EZ, using a semiology visualisation tool to generate probabilistic cortical heatmaps of involvement in seizures. RESULTS: Sixty-one individuals had FLE surgery over the study period. Twelve months following surgery, 28/61 (46%) were completely seizure-free, with a further eight experiencing only auras. Comparing the semiology database with the putative EZ, combined set-of-semiology correctly lateralised in 77% (95% CI: 69-85%), localised to the frontal lobe in 57% (95% CI: 48-67%), frontal lobe subregions in 52% (95% CI: 43-62%), and frontal gyri in 25% (95% CI: 16-33%). No difference in degree of correlation was seen comparing those with ongoing seizures 12 months after surgery to those seizure free. SIGNIFICANCE: Semiology alone was able to correctly lateralize the putative EZ in 77%, and localise to a sublobar level in approximately half of individuals who had FLE surgery. Semiology is not adequate alone and must be combined with imaging and EEG data to identify the epileptogenic zone.
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Epilepsia del Lóbulo Frontal , Humanos , Epilepsia del Lóbulo Frontal/diagnóstico , Epilepsia del Lóbulo Frontal/cirugía , Convulsiones/cirugía , Electroencefalografía/métodos , Lóbulo Frontal/cirugía , Imagen por Resonancia Magnética/métodos , Resultado del TratamientoRESUMEN
OBJECTIVES: In centers which routinely perform single fiber electromyography (SFEMG) for suspected myasthenia gravis (MG), the additional benefit of other neurophysiologic investigations and the frequency of myasthenia mimics has not been ascertained. We aimed to illustrate the range of neurological and non-neurological myasthenia mimics referred for evaluation, and contrast features of their electrophysiologic evaluation with confirmed MG. METHODS: We reviewed all SFEMG studies performed at our center between 1 January 2018 and 31 December 2020. Patient demographics, clinical phenotype, antibody status and final diagnosis were recorded. Electrophysiologic findings were correlated with clinical features and sensitivity analyses performed. RESULTS: A total of 528 SFEMG studies were performed, of which 213 (41%) were abnormal. A diagnosis of MG was made in 101 individuals, including 46 with ocular MG and 35 with seronegative disease. Compared to myasthenia mimics with an abnormal SFEMG, individuals with MG had higher median jitter (mean consecutive difference 61 µs vs. 42 µs, p < 0.001) and a greater percentage of abnormal pairs (61% vs. 33%, p < 0.001) on SFEMG. Repetitive nerve stimulation was abnormal in 27.1% of people with MG and was associated with a generalized clinical phenotype (OR 4.17; 95% CI 1.67-10.48). Thirteen (2%) individuals with MG had normal SFEMG, of whom 10 were in clinical remission. Functional neurological disorders, cranial nerve palsies, primary ocular disease and myopathy were frequent myasthenia mimics. CONCLUSION: SFEMG can be abnormal in a number of myasthenia mimics, and routine nerve conduction studies and electromyography should always be undertaken. In centers where SFEMG is performed routinely for the investigation of suspected MG, extensive proximal repetitive nerve stimulation can be foregone without substantially affecting diagnostic evaluation. Normal SFEMG in those with confirmed myasthenia gravis may help indicate clinical remission.
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Miastenia Gravis , Humanos , Electromiografía , Miastenia Gravis/diagnósticoRESUMEN
OBJECTIVE: Resective surgery for selected individuals with frontal lobe epilepsy can be effective, although multimodal outcomes are less established than in temporal lobe epilepsy. We describe long-term seizure remission and relapse patterns, psychiatric comorbidity, and socioeconomic outcomes following frontal lobe epilepsy surgery. METHODS: We reviewed individual data on frontal lobe epilepsy procedures at our center between 1990 and 2020. This included the presurgical evaluation, operative details and annual postoperative seizure and psychiatric outcomes, prospectively recorded in an epilepsy surgery database. Outcome predictors were subjected to multivariable analysis, and rates of seizure freedom were analyzed using Kaplan-Meier methods. We used longitudinal assessment of the Index of Multiple Deprivation to assess change in socioeconomic status over time. RESULTS: A total of 122 individuals with a median follow-up of seven years were included. Of these, 33 (27 %) had complete seizure freedom following surgery, with a further 13 (11 %) having only auras. Focal MRI abnormality, histopathology (focal cortical dysplasia, cavernoma or dysembryoplastic neuronal epithelial tumor) and fewer anti-seizure medications at the time of surgery were predictive of a favorable outcome; 67 % of those seizure-free for the first 12 months after surgery never experienced a seizure relapse. Thirty-one of 50 who had preoperative psychiatric pathology noticed improved psychiatric symptomatology by two years postoperatively. New psychiatric comorbidity was diagnosed in 15 (13 %). Persistent motor complications occurred in 5 % and dysphasia in 2 %. No significant change in socioeconomic deciles of deprivation was observed after surgery. SIGNIFICANCE: Favorable long-term seizure, psychiatric and socioeconomic outcomes can be seen following frontal lobe epilepsy surgery. This is a safe and effective treatment that should be offered to suitable individuals early.
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Epilepsia del Lóbulo Frontal , Epilepsia del Lóbulo Temporal , Electroencefalografía , Epilepsia del Lóbulo Frontal/cirugía , Epilepsia del Lóbulo Temporal/cirugía , Humanos , Recurrencia , Estudios Retrospectivos , Factores Socioeconómicos , Resultado del TratamientoRESUMEN
OBJECTIVE: To estimate the cost and time taken to evaluate adults with drug-resistant focal epilepsy for potentially curative surgery. METHODS: We reviewed data on 100 consecutive individuals at a tertiary referral center evaluated for epilepsy surgery in 2017. The time elapsed between referral and either surgery or a definitive decision not to progress was measured. National Health Service tariffs applicable to our setting were used to estimate the total cost of evaluation for individuals following different routes through the pre-surgical pathway. After surgery, self-reported seizure freedom rates were obtained from each individual to assess the approximate cost of pre-surgical evaluation per additional person seizure-free. RESULTS: Of 100 individuals evaluated, 27 had surgery, 63 had a definitive decision not to have surgery, and ten were awaiting further investigations. The median duration of the pre-surgical evaluation was 29.7 months (IQR 18.6-44.1 months), with a median cost per person of £9138 (IQR £6984-£14,868). Those who proceeded to Stage Two investigations (including fluorodeoxyglucose positron emission tomography, ictal single-photon emission computerized tomography and intracranial electroencephalography) had a higher cost and extended evaluation length. After a median of 3.1 (IQR 2.3-3.7) years, 15/27 people who had surgery were seizure-free. This equated to an approximate cost of £123,500 spent per additional person seizure-free. CONCLUSION: Pre-surgical evaluation is long and costly, particularly for those who require icEEG. For those with drug-resistant focal epilepsy, surgery is, however, associated with a greater chance of seizure freedom. The suitability and risk-benefit ratio of surgery should be considered at each step of the pre-surgical pathway.
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Epilepsia Refractaria , Epilepsias Parciales , Epilepsia , Adulto , Epilepsia Refractaria/diagnóstico por imagen , Epilepsia Refractaria/cirugía , Epilepsias Parciales/cirugía , Epilepsia/cirugía , Humanos , Convulsiones , Medicina EstatalRESUMEN
OBJECTIVE: To ascertain seizure outcomes in people with drug-resistant focal epilepsy considered for epilepsy surgery but who did not proceed. METHODS: We identified people discussed at a weekly presurgical epilepsy multi-disciplinary (MDT) meeting from January 2015 to December 2019 and in whom a decision not to proceed to surgery was made. Seizure outcomes were obtained from individuals, primary care physicians and attending neurologists at a minimum of 12 months following the not to proceed decision. RESULTS: We considered 315 people who did not proceed to surgery after evaluation. Nine died, and 25 were lost to follow-up. We included 281 people with a median follow-up of 2.4 (IQR 1.5-4) years. In total, 83 (30%) people reported that seizures had improved or resolved since the MDT meeting. Thirteen (5%) were seizure-free over the last 12 months of follow-up, 70 (25%) had experienced more than 50% reduction in seizure frequency, 180 (64%) had no meaningful change, and 18 (6%) reported a doubling of seizure frequency. Of the 53 (16%) who had vagal nerve stimulation, 19/53 (37%) reported more than 50% reduction in frequency, including one seizure-free. SIGNIFICANCE: The chances of seizure freedom with further medications and neurostimulation are low for people with drug-resistant focal epilepsy who have been evaluated for surgery and do not proceed, but improvement may still occur. Up to a quarter have a > 50% reduction in seizures, and one in twenty become seizure-free eventually. Trying additional anti-seizure medication and neurostimulation is worthwhile in this population.
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Epilepsia Refractaria , Epilepsias Parciales , Epilepsia , Estimulación del Nervio Vago , Epilepsia Refractaria/tratamiento farmacológico , Epilepsia Refractaria/cirugía , Epilepsias Parciales/tratamiento farmacológico , Epilepsias Parciales/cirugía , Humanos , Convulsiones/cirugía , Resultado del TratamientoRESUMEN
OBJECTIVE: This study was undertaken to determine reasons for adults with drug-resistant focal epilepsy who undergo presurgical evaluation not proceeding with surgery, and to identify predictors of this course. METHODS: We retrospectively analyzed data on 617 consecutive individuals evaluated for epilepsy surgery at a tertiary referral center between January 2015 and December 2019. We compared the characteristics of those in whom a decision not to proceed with surgical treatment was made with those who underwent definitive surgery in the same period. Multivariate logistic regression was performed to identify predictors of not proceeding with surgery. RESULTS: A decision not to proceed with surgery was reached in 315 (51%) of 617 individuals evaluated. Common reasons for this were an inability to localize the epileptogenic zone (n = 104) and the presence of multifocal epilepsy (n = 74). An individual choice not to proceed with intracranial electroencephalography (icEEG; n = 50) or surgery (n = 39), risk of significant deficit (n = 33), declining noninvasive investigation (n = 12), and coexisting neurological comorbidity (n = 3) accounted for the remainder. Compared to 166 surgically treated patients, those who did not proceed to surgery were more likely to have a learning disability (odds ratio [OR] = 2.35, 95% confidence interval [CI] = 1.07-5.16), normal magnetic resonance imaging (OR = 4.48, 95% CI = 1.68-11.94), extratemporal epilepsy (OR = 2.93, 95% CI = 1.82-4.71), bilateral seizure onset zones (OR = 3.05, 95% CI = 1.41-6.61) and to live in more deprived socioeconomic areas (median deprivation decile = 40%-50% vs. 50%-60%, p < .05). SIGNIFICANCE: Approximately half of those evaluated for surgical treatment of drug-resistant focal epilepsy do not proceed to surgery. Early consideration and discussion of the likelihood of surgical suitability or need for icEEG may help direct referral for presurgical evaluation.
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Epilepsia Refractaria , Epilepsias Parciales , Epilepsia , Adulto , Epilepsia Refractaria/diagnóstico , Epilepsia Refractaria/cirugía , Electroencefalografía/métodos , Epilepsias Parciales/diagnóstico , Epilepsias Parciales/cirugía , Epilepsia/diagnóstico , Epilepsia/cirugía , Humanos , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos , Convulsiones/cirugía , Resultado del TratamientoRESUMEN
INTRODUCTION: Mitochondrial diseases exhibit wide phenotypic heterogeneity, and can present as progressive myoclonic epilepsy. SUMMARY: We report a case of adult-onset drug-resistant epilepsy, cortical myoclonus and bilateral optic neuropathies due to m.14487T>C, a rare mitochondrial gene mutation identified on whole-genome sequencing. This mutation, which affects the NADH dehydrogenase 6 (ND6) subunit of the mitochondrial respiratory chain, is most commonly implicated in cases of infantile-onset Leigh syndrome, although a broader phenotypic spectrum including migraine with aura and progressive myoclonic epilepsy have been described. Serial MRI scans over a 2-year period demonstrated the interval development of bihemispheric stroke-like lesions. Giant somatosensory evoked potentials and short-duration myoclonic jerks with craniocaudal spread on surface electromyography were consistent with cortical myoclonus. Optical coherence tomography showed bilateral symmetric thinning of the nerve fibre layer in the papillomacular bundles. CONCLUSION: Whole-genome sequencing can help to provide a definitive diagnosis for mitochondrial disease and should be considered in situations where clinical suspicion remains high despite normal genetic panels or muscle histopathology. Mitochondrial disease can present as adult-onset progressive myoclonic epilepsy, and bilateral optic neuropathies can be a striking feature of ND6 mitochondrial gene mutations. In our case, severe cortical myoclonus affecting speech and swallowing remained highly drug-resistant, however, symptomatic benefit was derived from targeted onabotulinum toxin A injections.
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This study provides contemporary data on patients admitted to a Neurology unit with seizures, the majority of whom have a diagnosis of epilepsy. There were 278 hospital presentations with seizure during the 6-month study period, with 60 admissions to the Neurology unit included for analysis. Provoking factors were identified in 40%, with poor medication adherence the commonest precipitant. CT-brain had low diagnostic yield in patients with epilepsy presenting with seizure and should be reserved for those with further indications for imaging. Patients with drug-resistant epilepsy comprised 54% of admissions suggesting management strategies in this cohort can be further optimized.
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Epilepsia/diagnóstico , Admisión del Paciente/estadística & datos numéricos , Habitaciones de Pacientes/estadística & datos numéricos , Adulto , Anciano , Distribución de Chi-Cuadrado , Minería de Datos , Epilepsia/epidemiología , Femenino , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Neurología/estadística & datos numéricos , Habitaciones de Pacientes/organización & administración , Estudios Prospectivos , Australia del Sur/epidemiologíaAsunto(s)
Betacoronavirus , Tronco Encefálico , Infecciones por Coronavirus/complicaciones , Encefalitis/diagnóstico , Encefalitis/etiología , Neumonía Viral/complicaciones , Anciano , COVID-19 , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/terapia , Encefalitis/terapia , Femenino , Humanos , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/terapia , SARS-CoV-2RESUMEN
Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a weekly virtual coronavirus disease 19 (COVID-19) neurology multi-disciplinary meeting was established at the National Hospital, Queen Square, in early March 2020 in order to discuss and begin to understand neurological presentations in patients with suspected COVID-19-related neurological disorders. Detailed clinical and paraclinical data were collected from cases where the diagnosis of COVID-19 was confirmed through RNA PCR, or where the diagnosis was probable/possible according to World Health Organization criteria. Of 43 patients, 29 were SARS-CoV-2 PCR positive and definite, eight probable and six possible. Five major categories emerged: (i) encephalopathies (n = 10) with delirium/psychosis and no distinct MRI or CSF abnormalities, and with 9/10 making a full or partial recovery with supportive care only; (ii) inflammatory CNS syndromes (n = 12) including encephalitis (n = 2, para- or post-infectious), acute disseminated encephalomyelitis (n = 9), with haemorrhage in five, necrosis in one, and myelitis in two, and isolated myelitis (n = 1). Of these, 10 were treated with corticosteroids, and three of these patients also received intravenous immunoglobulin; one made a full recovery, 10 of 12 made a partial recovery, and one patient died; (iii) ischaemic strokes (n = 8) associated with a pro-thrombotic state (four with pulmonary thromboembolism), one of whom died; (iv) peripheral neurological disorders (n = 8), seven with Guillain-Barré syndrome, one with brachial plexopathy, six of eight making a partial and ongoing recovery; and (v) five patients with miscellaneous central disorders who did not fit these categories. SARS-CoV-2 infection is associated with a wide spectrum of neurological syndromes affecting the whole neuraxis, including the cerebral vasculature and, in some cases, responding to immunotherapies. The high incidence of acute disseminated encephalomyelitis, particularly with haemorrhagic change, is striking. This complication was not related to the severity of the respiratory COVID-19 disease. Early recognition, investigation and management of COVID-19-related neurological disease is challenging. Further clinical, neuroradiological, biomarker and neuropathological studies are essential to determine the underlying pathobiological mechanisms that will guide treatment. Longitudinal follow-up studies will be necessary to ascertain the long-term neurological and neuropsychological consequences of this pandemic.
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Infecciones por Coronavirus , Enfermedades del Sistema Nervioso , Pandemias , Neumonía Viral , Adolescente , Corticoesteroides/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Betacoronavirus/patogenicidad , COVID-19 , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/epidemiología , Utilización de Medicamentos/estadística & datos numéricos , Femenino , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Londres/epidemiología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/líquido cefalorraquídeo , Enfermedades del Sistema Nervioso/diagnóstico por imagen , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Enfermedades del Sistema Nervioso/epidemiología , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/epidemiología , Estudios Retrospectivos , SARS-CoV-2 , Adulto JovenRESUMEN
Chronic inflammatory demyelinating polyneuropathy (CIDP) is characterised by significant clinical heterogeneity and as such reliable biomarkers are required to measure disease activity and assess treatment response. Recent advances in our understanding of disease pathogenesis and the discovery of novel serum-based, electrophysiologic and imaging biomarkers allow clinicians to make more informed decisions regarding individualised treatment regimes. As a chronic immune-mediated process typified by relapse following withdrawal of immunomodulatory therapy, a substantial proportion of patients with CIDP require long term treatment with intravenous immunoglobulin (IVIg), a scarce and expensive donor-derived resource. The required duration and intensity of immunoglobulin treatment vary widely between individuals, highlighting both the heterogeneous nature of the underlying disease process as well as the variable pharmacologic properties of IVIg. This review outlines the use of multimodal biomarkers in the longitudinal evaluation of nerve injury and how recent developments have impacted our ability to predict both response to immunoglobulin administration and its withdrawal.
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A rare extramedullary manifestation of haematological malignancy, myeloid sarcoma is most commonly seen in patients with acute myeloid leukaemia. We report on an adult patient who presented with an atypical phenotype of progressive cranial neuropathy without blood or bone marrow involvement, and in whom obtaining material for pathological diagnosis was made challenging by unusual findings of absent fluorodeoxyglucose-positron emission tomography avidity and involvement of sites not readily accessible to biopsy (orbital apex and cauda equina). The eventual diagnosis was obtained through biopsy of the uterine cervix before being verified on repeat lymph node and cerebrospinal fluid sampling prior to initiation of chemotherapy.
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The study aimed to determine the effects of mild exertional heat stress on intestinal injury, permeability, gastrointestinal symptoms, and systemic endotoxin and cytokine responses. Ten endurance runners completed 2 h of running at 60% VÌO2max in warm (WARM: 30°C) and temperate (TEMP: 22°C) ambient conditions. Rectal temperature (Tre) and gastrointestinal symptoms were recorded every 10 min during exercise. Blood samples were collected pre- and post-exercise, and during recovery to determine plasma intestinal fatty acid-binding protein (I-FABP) and cortisol concentrations, and systemic endotoxin and inflammatory cytokine profiles. Urinary lactulose:L-rhamnose ratio (L/R) was used to measure small intestine permeability. Compared with TEMP, WARM significantly increased Tre from 50 min onwards (38.1±0.3°C vs. 38.4±0.5°C, respectively; p<0.01), gastrointestinal symptoms (p=0.017), post-exercise plasma cortisol (26% vs. 59%, respectively; p<0.001) and I-FABP (127% vs. 184%, respectively; p<0.001) concentrations. Circulatory anti-endotoxin antibodies increased post-exercise (p<0.001) on WARM (20%) and TEMP (28%). No differences were observed for plasma endotoxin concentration (6% vs. 5% increase, respectively) or small intestine permeability (L/R 0.026±0.010 and 0.025±0.015, respectively). Both pro- and anti-inflammatory cytokines increased post-exercise, with inflammatory response cytokines TNF-α (p=0.015) and IL-8 (p=0.044), and compensatory anti-inflammatory cytokines IL-10 (p=0.065), and IL-1ra higher on WARM than TEMP. Findings suggest that exposure to warm ambient conditions during prolonged submaximal running induces transient intestinal epithelial injury, increases gastrointestinal symptoms, and promotes greater perturbations to the systemic cytokine profile compared to running in temperate conditions.
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PURPOSE: The study aimed to determine the effects of exertional-heat stress on gastrointestinal integrity, symptoms, systemic endotoxin and inflammatory responses; and assess the relationship between changes in body temperature and gastrointestinal perturbations. METHODS: Ten endurance runners completed 2 h running at 60% [Formula: see text]O2max in hot (HOT: 35 °C) and temperate (TEMP: 22 °C)-ambient conditions. Rectal temperature (T re) and gastrointestinal symptoms were recorded every 10 min during exercise. Blood samples were collected pre- and post-exercise, and during recovery to determine plasma intestinal fatty acid binding protein (I-FABP), cortisol, bacterial endotoxin and cytokine profile. Calprotectin was determined from pre- and post-exercise faecal samples. Urinary lactulose:L-rhamnose ratio was used to measure intestinal permeability. RESULTS: Compared with TEMP, HOT significantly increased T re (1.4 ± 0.5 vs 2.4 ± 0.8 °C, p < 0.001), cortisol (26 vs 82%, p < 0.001), I-FABP (127 vs 432%, p < 0.001), incidence (70 vs 90%) and severity (58 counts vs 720 counts, p = 0.008) of total gastrointestinal symptoms. Faecal calprotectin and circulating endotoxin increased post-exercise in both trials (mean increase 1.5 ± 2.5 µg/g, p = 0.032, and 6.9 ± 10.3 pg/ml, p = 0.047, respectively), while anti-endotoxin antibodies increased 28% post-exercise in TEMP and decreased 21% in HOT (p = 0.027). However, intestinal permeability did not differ between trials (p = 0.185). Inflammatory cytokines were greater on HOT compared to TEMP (p < 0.05). Increases in T re were positively associated with I-FABP, IL-10, cortisol, nausea and urge to regurgitate (p < 0.05). CONCLUSIONS: Exertional-heat stress induces a thermoregulatory strain that subsequently injures the intestinal epithelium, reduces endotoxin clearance capacity, promotes greater cytokinaemia, and development of gastrointestinal symptoms.
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Citocinas/sangre , Endotoxinas/sangre , Respuesta al Choque Térmico , Absorción Intestinal , Esfuerzo Físico , Adulto , Ejercicio Físico , Femenino , Humanos , Hidrocortisona/sangre , Reflujo Laringofaríngeo/etiología , Masculino , Náusea/etiologíaRESUMEN
Exertional heat stress (EHS) disturbs the integrity of the gastrointestinal tract leading to endotoxaemia and cytokinaemia, which have symptomatic and health implications. This study aimed to determine the effects of carbohydrate and protein intake during EHS on gastrointestinal integrity, symptoms, and systemic responses. Eleven (male, n = 6; female, n = 5) endurance runners completed 2 h of running at 60% maximal oxygen uptake in 35 °C ambient temperature on 3 occasions in randomised order, consuming water (WATER), 15 g glucose (GLUC), or energy-matched whey protein hydrolysate (WPH) before and every 20 min during EHS. Rectal temperature and gastrointestinal symptoms were recorded every 10 min during EHS. Blood was collected pre- and post-EHS, and during recovery to determine plasma concentrations of intestinal fatty-acid binding protein (I-FABP) as a marker of intestinal epithelial injury, cortisol, endotoxin, and inflammatory cytokines. Urinary lactulose/l-rhamnose ratio was used to measure small intestine permeability. Compared with WATER, GLUC, and WPH ameliorated EHS associated intestinal epithelial injury (I-FABP: 897 ± 478 pg·mL-1 vs. 123 ± 197 pg·mL-1 and 82 ± 156 pg·mL-1, respectively, p < 0.001) and small intestine permeability (lactulose/l-rhamnose ratio: 0.034 ± 0.014 vs. 0.017 ± 0.005 and 0.008 ± 0.002, respectively, p = 0.001). Endotoxaemia was observed post-EHS in all trials (10.2 pg·mL-1, p = 0.001). Post-EHS anti-endotoxin antibodies were higher (p < 0.01) and cortisol and interleukin-6 lower (p < 0.05) on GLUC than WATER only. Total and upper gastrointestinal symptoms were greater on WPH, compared with GLUC and WATER (p < 0.05), in response to EHS. In conclusion, carbohydrate and protein intake during EHS ameliorates intestinal injury and permeability. Carbohydrate also supports endotoxin clearance and reduces stress markers, while protein appears to increase gastrointestinal symptoms, suggesting that carbohydrate is a more appropriate option.