Title: Hypoglycemic Encephalopathy: A Case Series and Literature Review on Outcome

Determination

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Acknowledgments We are grateful to Otmar Huber for skillful assistance and support. Detemir led to
a greater response of autonomic and neuroglycopenic symptoms, albeit at lower blood glucose levels
than human insulin, which would suggest a lowering of the awareness of hypoglycemia. DWI on
admission shows hyperintense lesions in the IC, CR, and CS ( A ) with reduced ADC values (
arrows, B ). Furthermore, we were not able to perform an EMBASE search, since we were not able
to gain access to this database through the means supplied by our institution. Six of them died, two
were lost to follow-up, five had a long-term good outcome and two had a poor outcome. The
topography of the lesions did not display any prognostic value. Case study, Radiopaedia.org
(Accessed on 22 Feb 2024). Nine patients who underwent care limitation, including three patients
with withdrawal of care, survived to ICU discharge, all with a final poor outcome. MR imaging of
hypoglycemic encephalopathy: lesion distribution and prognosis prediction by diffusion-weighted
imaging. While some subsets within the retrieved studies could be identified, due to the
aforementioned differences this review format did not lend itself to a statistical analysis. Some
theories are based on cell damage due to increased extracellular aspartate and glutamate 7. His vital
signs on arrival at the emergency department were normal. Diffusion MR imaging of hypoglycemic
encephalopathy. As already known, hypoglycemic encephalopathy is more common in diabetic
patients and diabetes was associated with poor outcome in univariate, but no longer in multivariate
analysis. He was intubated and was transferred to the intensive care unit. Cytologic and
microbiologic investigations had negative results, as did investigations for other metabolic and toxic
causes. Previous Article in Journal Structural Perspective on Revealing and Altering Molecular
Functions of Genetic Variants Linked with Diseases. Seeking to identify predictive variables of long-
term outcome useful in daily practice, we found that low mRS prior to ICU admission and the
absence of abnormalities on first brain imaging were significantly, although not strongly, predictive
of outcome. Selection biases cannot be excluded regarding the non-responding invited ICU centers.
Journal of Functional Morphology and Kinesiology (JFMK). A, Initial DWI on admission shows
hyperintense lesions in the IC and CR, with reduced ADC values. Editors select a small number of
articles recently published in the journal that they believe will be particularly. Hypoglycemic
encephalopathy is a neurologic manifestation of hypoglycemia. Computed tomography of the brain
showed no abnormality. Severe hypoglycemia in a juvenile diabetic rat model: presence and severity
of seizures are associated with mortality. PLoS ONE. 2013;8(12):e83168. Article. Conflicts of
Interest The authors declare no conflicts of interest. Fifteen French adult ICUs were invited to
participate in the study in September 2015. Oral amino acids administered during a hypoglycemic
clamp raised glucagon levels in both healthy and T1DM participants. Specific characteristics of other
neuroprotective strategies. Apart from an apparently deleterious influence on the central nervous
system, hypoglycemic episodes furthermore possess the potential to damage the peripheral nervous
system as well.
Whatever the explanation of our findings, early-onset seizures should not be considered at least as
adding more clinical severity in prolonged hypoglycemic encephalopathy. They included also
patients with “hypoglycemic consciousness disturbance” which regained consciousness immediately
after glucose administration, while our population was only constituted of severe patients requiring
ICU because of a persistent coma over 24 h. Table 3 Characteristics of patients with or without a
decision of care limitation Full size table. Preceding studies by the same research group had revealed
that both recurrent hypoglycemia (RH) and diabetic rats showed increased extracellular lactate levels
and higher extracellular GABA concentrations in the VMH. Chan et al. therefore hypothesized that
in these conditions, the body’s adaption to, among other things, the alternate fuel substrate lactate
and its subsequently elevated levels leads to counter-regulatory failure during RH. Some theories are
based on cell damage due to increased extracellular aspartate and glutamate 7. Results Among the 15
ICUs invited to participate, one reported that no patient fulfilled the inclusion criteria; nine admitted
in the study period at least one patient that fulfilled the inclusion criteria and five provided no
information. Case of steroid-responsive encephalopathy from hypoglycaemia Google Scholar More
in this TOC Section. Similarly, in order to be as inclusive as possible regarding the employed study
design, we decided against defining a temporal limitation of the intervention’s administration with
respect to the hypoglycemia experiment. Otherwise swelling and oedema of the cortex, caudate and
lentiform nuclei. A review protocol was registered in the PROSPERO database. Influence of Sleep
Deprivation on Hypoglycemia Utilizing a number of cognitive tests, Inkster et al. Consequently, we
retrieved a variety of differing approaches and were able to qualitatively assess them. Cohort studies
have suggested that as many as 15% of patients with insulin-treated type 2 diabetes have at least one
episode of severe hypoglycemia. 1 Although the prevalence is not known, hypoglycemic
encephalopathy is a potentially life-threatening manifestation of hypoglycemia, which can present
with seizures, altered mental status or focal neurologic deficits. Severe hypoglycaemia, mild
cognitive impairment, dementia and brain volumes in older adults with type 2 diabetes: the
Atherosclerosis Risk in Communities (ARIC) cohort study. Oral amino acids administered during a
hypoglycemic clamp raised glucagon levels in both healthy and T1DM participants. A 45-year-old
man (patient 11) was found in a coma. Furthermore, we were not able to perform an EMBASE
search, since we were not able to gain access to this database through the means supplied by our
institution. Ten to fifteen days with no clinical improvement could be a minimal threshold, based on
the minimal time from admission to decision of therapeutic limitation among the patients who
survived their ICU stay. This article is an open access article distributed under the terms and
conditions of the Creative Commons Attribution (CC BY) license ( ). Journal of Pharmaceutical and
BioTech Industry (JPBI). This discrepancy may be explained by several reasons. Hypoglycemic and
hypoxic on scene, with long acting insulin pen in possession. Since we anticipated the number of
results to be relatively low and we wanted to produce as comprehensive an overview of the current
state of the research as possible, we decided to include both animal experiments and human studies.
International Journal of Molecular Sciences. 2019; 20(3):550. Hypoglycemic Encephalopathy: A
Neurologic Manifestation of Hypoglycemia. Impact of early-onset seizures on grading and outcome
in patients with subarachnoid hemorrhage. A Systematic Review of Neuroprotective Strategies in the
Management of Hypoglycemia. Nistor, Marius, Martin Schmidt, Isabel Graul, Florian Rakers, and
Rene Schiffner. For this purpose, 10 healthy volunteers, 10 T1DM patients with IAH, and 10 T1DM
patients with normal awareness of hypoglycemia (NAH) participated in a crossover trial on two
occasions, undergoing a hypoglycemic clamp subsequent to either a bout of HIIT or a rest period.
Disagreements were resolved through discussion and consensus.
To our knowledge, this study has the largest population of prolonged hypoglycemic encephalopathy
requiring ICU hospitalization. Whatever the explanation of our findings, early-onset seizures should
not be considered at least as adding more clinical severity in prolonged hypoglycemic
encephalopathy. Since pyruvate metabolization does not depend on cytosolic NAD, Choi et al.
However, some patients with severe impairment at ICU discharge may improve later, suggesting that
therapeutic limitation should not be decided early. A Systematic Review of Neuroprotective
Strategies in the Management of Hypoglycemia. Int. J. Mol. Sci. 2019, 20, 550. B, Follow-up DWI
obtained 4 days after symptom improvement shows that the hyperintense lesions have disappeared,
with normalization of ADC values. Overall, risk of bias across studies was medium to low, albeit a
number of studies exhibited an unclear risk of bias in several categories due to insufficient reporting.
An overview of the specific study characteristics and an overview of the respective parameters used
by individual studies is provided in Table 4. Feature papers represent the most advanced research
with significant potential for high impact in the field. A Feature. Conflicts of Interest The authors
declare no conflicts of interest. In addition, several patients did not undergo brain MRI, a more
sensitive tool than CT scan, and four of them had no imaging at all. Cerebral MRI, especially DWI,
is an important tool for the diagnosis and predictive of prognosis of this condition 1,2,4-6. All of the
human participants were above 18 years old. Acknowledgements The authors thank Ms. Ryoko Ono
for editing the images. Causes of hypoglycemia were various, mainly including insulin or oral
antidiabetic drugs abuse (65%) and neuroendocrine carcinoma (16%). The duration of hypoglycemia
was not entered in the statistical analysis since values were unknown in 22 patients. We diagnosed
hypoglycemic encephalopathy, likely from repeated episodes of hypoglycemia. Furthermore, we
were not able to perform an EMBASE search, since we were not able to gain access to this database
through the means supplied by our institution. Of a total of 16,230 results, 145 were assessed in full-
text form: 27 articles adhered to the inclusion criteria and were qualitatively analyzed. Please let us
know what you think of our products and services. Morphological evaluation revealed a moderate
region-specific protective effect on the caudoputamen and hippocampus, albeit only during
halothane anesthesia. Furthermore, 1-week follow-up was probably too short to fully evaluate this
pathology. Diffusion-weighted MRI predicts prognosis in severe hypoglycemic encephalopathy.
Considering the rising prevalence of diabetes mellitus in the population, we investigated
neuroprotective strategies during hypoglycemia in the form of a systematic review in adherence to
the PRISMA statement. Available published data on prognosticators in prolonged hypoglycemic
encephalopathy are based on cases series with a limited number of patients. Table 3 Characteristics of
patients with or without a decision of care limitation Full size table. Studies that observed human
participants with a history of other illnesses, as reported by the authors, that potentially alter cerebral
physiology, such as stroke, traumatic brain injury, epilepsy, neurodegenerative diseases, etc., were
therefore excluded. Theophylline increased epinephrine, norepinephrine, and cortisol response in
both participant groups and ameliorated hypoglycemia-induced CBF increase, albeit significantly
more in T1DM participants. Magnetic resonance imaging (MRI) revealed abnormal diffusion
restriction involving the cerebral cortex in multiple locations (Figure 1), with the changes most
confluent and pronounced in the right parieto-occipital cortex. A poor prognosis was observed in
31(63%) patients including 20 ICU non-survivors, two follow-up non-survivors and nine survivors
(Fig. 1 ). Noteworthy, six patients who were discharged from the ICU with poor functional status
improved their mRS at 1-year follow-up, including five who reached the good outcome group.
Pre-defined search strategies were utilized that were adapted to the respective database’s search
algorithm. It is known that hypoglycemia leads to cellular energy failure, as the brain is an obligate
glucose metabolizer. SGi was involved in statistical analysis, analysis and interpretation of the data,
and drafting the manuscript. Disagreements were resolved through discussion and consensus. 4.8.
Summary Measures and Analysis This review employed a qualitative summary and narrative analysis
of the retrieved results. Disagreements were resolved through discussion and consensus. Causes of
hypoglycemia were various, mainly including insulin or oral antidiabetic drugs abuse (65%) and
neuroendocrine carcinoma (16%). International Journal of Translational Medicine (IJTM). While on a
study level, the individual results appeared promising, more research is required to investigate not
only specific neuroprotective strategies against hypoglycemic cerebral damage, but also its
underlying pathophysiological mechanisms. Paper should be a substantial original Article that
involves several techniques or approaches, provides an outlook for. International Journal of
Molecular Sciences. 2019; 20(3):550. Otherwise swelling and edema of the cortex, caudate and
lentiform nuclei. PEB was involved in conception and design, data acquisition, analysis and
interpretation of the data, and drafting the manuscript. A further field of concern regarding
potentially harmful hypoglycemic states is that of neonatal hypoglycemia, which can occur after birth
due to a child’s conversion from an exogenous maternal glucose supply in utero to endogenous
glycogenolysis and gluconeogenesis. He was intubated and was transferred to the intensive care unit.
Cytologic and microbiologic investigations had negative results, as did investigations for other
metabolic and toxic causes. Download citation Received: 28 December 2011 Revised: 19 February
2012 Accepted: 12 March 2012 Published: 11 April 2012 Issue Date: October 2012 DOI: Share this
article Anyone you share the following link with will be able to read this content: Get shareable link
Sorry, a shareable link is not currently available for this article. According to French law on
noninterventional and retrospective studies, patients received written information about the study
and non-opposition to their participation in the study was sought. Efforts should be made to reduce
potential sources of bias and to standardize experimental models and designs to increase the
translational value of subsequent research. To preserve the internal coherence of the review, we
therefore presented all results in narrative form. 5. Conclusions A systematic literature search of three
medical databases regarding neuroprotective strategies during hypoglycemia yielded only a small
number of studies, although both human studies and animal experimental studies were included.
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The objective of this multicenter study was to study causes, initial consequences and the vital and
functional long-term prognosis of patients admitted to the ICU with prolonged neurological
manifestations related to obvious hypoglycemia. Editor’s Choice articles are based on
recommendations by the scientific editors of MDPI journals from around the world. DWI on
admission shows hyperintense lesions in the IC, CR, and CS (A) with reduced ADC values (arrows,
B). The splenium of the corpus callosum can also be affected, producing the so-called boomerang
sign. While some subsets within the retrieved studies could be identified, due to the aforementioned
differences this review format did not lend itself to a statistical analysis. For many patients, time
between hypoglycemia onset and first glucose administration was impossible to precisely assess.
Severe hypoglycaemia, mild cognitive impairment, dementia and brain volumes in older adults with
type 2 diabetes: the Atherosclerosis Risk in Communities (ARIC) cohort study. Additional results
would allow relevant advice to be given to specific patient groups concerning the sort and extent of
exercise that can be recommended, and which should be avoided. Rooijackers et al.’s experimental
study evaluated the effects of high-intensity interval training (HIIT) on subsequently reduced
reactions to hypoglycemia through lactate elevation. Counter-regulatory hormone levels did not differ
between the two interventions.
In the present study, lesion localization at first imaging (including MRI and CT scan) was not
predictive of outcome but normal early imaging that was mostly observed in brain CT scans was
considered as a factor of good outcome. Magnetic resonance imaging (MRI) revealed abnormal
diffusion restriction involving the cerebral cortex in multiple locations (Figure 1), with the changes
most confluent and pronounced in the right parieto-occipital cortex. Primary exclusion criteria were
aspects in the investigated studies that did not adhere to our PICOS criteria. DWI on admission
shows hyperintense lesions in the IC, CR, and CS (A) with reduced ADC values (arrows, B). Based
on a predefined inclusion protocol, results were screened and evaluated by two researchers. PEB was
involved in conception and design, data acquisition, analysis and interpretation of the data, and
drafting the manuscript. An initial screening of titles and abstracts based on our PICOS
characteristics led to the exclusion of 16,085 studies. Lactate reduced the glucose threshold at which
four-choice reaction time deteriorated and delayed counter-regulatory hormone release of adrenaline,
noradrenaline, growth hormone, and cortisol, while glucagon release remained unaffected. Moreover,
for the first time, we document gender differences in fear of hypoglycaemia, suggesting that females
are more affected by fear of hypoglycaemia than men. Predictors of outcome in hypoglycemic
encephalopathy. Changes in human brain glutamate concentration during hypoglycemia: insights into
cerebral adaptations in hypoglycemia-associated autonomic failure in type 1 diabetes. In both human
and animal studies, the reporting of appropriate measures against selection bias was very imprecise
and therefore prevented an accurate evaluation of this important aspect. Duration of hypoglycemia
was a significant predictor of outcome in univariate analysis, but was not included in the multivariate
analysis due to several missing data. Our population was small due to the scarcity of this disease,
and a larger population would have allowed a more robust multivariate analysis. Twenty-two (45%)
patients underwent therapeutic limitation, mainly related to no expected hope for improvement. A,
DWI shows bilaterally asymmetric confluent hyperintense lesions in the frontal, parietal, insular,
temporal, occipital cortices, and BG. Download citation Received: 04 November 2016 Accepted: 08
May 2017 Published: 22 May 2017 DOI: Share this article Anyone you share the following link with
will be able to read this content: Get shareable link Sorry, a shareable link is not currently available
for this article. However, normal brain CT scans were significantly more frequent than normal MRIs
( P Table 2 Type and results of imaging Full size table. Our systematic search was therefore designed
to be broad and to include as many related articles as possible. Overall risk of bias across studies
was medium to low. We use cookies on our website to ensure you get the best experience.
Furthermore, 1-week follow-up was probably too short to fully evaluate this pathology. A Systematic
Review of Neuroprotective Strategies in the Management of Hypoglycemia. A multiple stepwise
logistic regression model was established with any covariate with univariate significance of P value
Ethical considerations The study was approved by the Ethics Committee of the French Language
Society of Critical Care Medicine. Case report: hypoglycemia and diffusion-weighted imaging. This
discrepancy may be explained by several reasons. Journal of Pharmaceutical and BioTech Industry
(JPBI). Diffusion-weighted MR imaging in early diagnosis and prognosis of hypoglycemia.
International Journal of Turbomachinery, Propulsion and Power (IJTPP). Finally, mRS assessment
was not based on a standardized questionnaire, which could have led to possible mistakes.
All patient groups exhibited a similar endogenous elevation of lactate levels after exercise, with a
suppression of growth hormone and cortisol but unchanged catecholamine response as compared to
rest. NMDA- and AMPA-Receptor Blockade Based on previous research that showed that sustained
post-hypoglycemic neuronal damage is at least partly caused by excitatory amino acids, Nellgard et
al. While individually promising, further research into the potential neuroprotective properties of
these substances is needed, as well as their potential side effects. The differential diagnosis includes
hypoxic encephalopathy and an atypical posterior reversible encephalopathy syndrome. Diffusion-
weighted MR imaging in early diagnosis and prognosis of hypoglycemia. Case study,
Radiopaedia.org (Accessed on 22 Feb 2024). Forty-one patients (84%) were hospitalized in the ICU
within the first 24 h after the presumed onset of hypoglycemia and the eight remaining patients
between 24 and 48 h. Restricted diffusion can be an earlier and sensitive tool, and is commonly
reversible. Previous Article in Special Issue Post-Injury Neuroprotective Effects of the Thalidomide
Analog 3,6?-Dithiothalidomide on Traumatic Brain Injury. In contrast to control animals, 3dRH
animals exhibited an elevated lactate uptake, glucose oxidization, and tricarboxylic acid (TCA) cycle.
The remaining 27 studies matched our inclusion criteria and were qualitatively assessed. Abnormal
diffusion restriction through these involved structures. Feature papers represent the most advanced
research with significant potential for high impact in the field. A Feature. While on a study level, the
individual results appeared promising, more research is required to investigate not only specific
neuroprotective strategies against hypoglycemic cerebral damage, but also its underlying
pathophysiological mechanisms. Nistor, Marius, Martin Schmidt, Isabel Graul, Florian Rakers, and
Rene Schiffner. Continuous EEG monitoring, never performed here could have been more relevant
to rule out subclinical status epilepticus or better delineate patterns with prognosis value. Apart from
the potential risk of death during severe hypoglycemic episodes, a further concern regarding
recurrent episodes of hypoglycemia is cerebral damage. While we are confident in presenting a
somewhat comprehensive summary of the review question, we cannot preclude the possibility that
due to the broadness of our search protocol, some eligible studies were not covered. To our
knowledge, a review about this particular aspect of the side effects of hypoglycemia in the context of
potential protective strategies has not been performed up to this point. Hypoglycemia, with organic
acidemia, ketonuria, and hyperammonemia were found at examination. Finally, the present findings
offer prognostic tools, which need to be further delineated in larger, prospective investigations. The
remaining 145 studies were retrieved and assessed in full-text form, which resulted in the subsequent
exclusion of another 118 studies. International Journal of Turbomachinery, Propulsion and Power
(IJTPP). Influence of Sleep Deprivation on Hypoglycemia Utilizing a number of cognitive tests,
Inkster et al. References ? Akram K, Pedersen-Bjergaard U, Borch-Johnsen K, et al. However, some
patients with severe impairment at ICU discharge may improve later, suggesting that therapeutic
limitation should not be decided early. The Hypoglycaemia Fear Survey - Aloneness subscale was
significantly associated with frequency of severe hypoglycaemia, number of symptoms during mild
hypoglycaemia, gender, frequency of mild hypoglycaemia, HbA(1c), hypoglycaemic unawareness
and visits to the emergency room because of severe hypoglycaemia. Seeking to identify predictive
variables of long-term outcome useful in daily practice, we found that low mRS prior to ICU
admission and the absence of abnormalities on first brain imaging were significantly, although not
strongly, predictive of outcome. Our population was small due to the scarcity of this disease, and a
larger population would have allowed a more robust multivariate analysis.