Corticosteroid-induced hyperammonaemic encephalopathy in a woman with late-onset ornithine transcarbamylase deficiency.

Ornithine transcarbamylase deficiency (OTCD) is a rare, X linked disorder that can manifest in late adulthood in heterozygous females as severe hyperammonaemia following environmental stressors. We present a case of hyperammonaemic encephalopathy that was triggered by glucocorticoid administration in an adult woman with heterozygous OTCD with clinical response to haemodialysis, ammonia scavengers and a high-calorie, low-protein diet.

[A case of COVID-associated encephalopathy in a patient with multiple sclerosis]. / Klinicheskii sluchai COVID-assotsiirovannoi entsefalopatii u patsienta s rasseyannym sklerozom.

A case of acute encephalopathy manifested with impaired consciousness, hemichorrhea, speech and cognitive impairment in a female patient with COVID-19 and multiple sclerosis is presented. In the literature, there are isolated reports of such a combination of diseases, and therefore difficulties arise in carrying out differential diagnosis and prescribing therapy. Given the limited knowledge about the long-term consequences of COVID-19, systematic analysis of such cases and follow-up of such patients is necessary.

A rare case of bilateral frontal lobe lesions due to thyroid storm.

Thyroid storm is a rare but well-known life-threatening complication that occurs due to acute exacerbation of thyrotoxicosis with the increased levels of circulating thyroid hormones. Reports of metabolic encephalopathy associated with thyroid storm are scarce. We describe the case of a 23-year-old male patient with no previous history of abnormal thyroid function who had consumed excessive amounts of alcohol before disease onset. The patient was found unconscious and febrile on a roadside by a passerby and was admitted to our hospital's emergency department. His primary clinical presentation included hyperthermia (40.8 °C), nodal tachycardia (180 beats/min), seizures, coma, and hypoglycemia (2.18 mmol/L). The hypoglycemia was quickly corrected after admission, but his level of consciousness showed no improvement. With aggressive screening, the patient was found to have severe thyroid dysfunction (T3 = 6.67 nmol/L, T4 = 252.00 nmol/L, free T3 = 29.20 pmol/L, free T4 = 65.30 pmol/L, and TSH = 0.001 µIU/mL). After medical treatment, plasmapheresis, hemofiltration, and hemoperfusion, the patient showed substantial improvement in thyroid hormone levels and stabilization of vital signs, but the impaired consciousness and seizures persisted. Multiple computed tomography scans revealed brain abnormalities. Magnetic resonance imaging performed after tracheal extubation revealed bilateral frontal lobe lesions. We reported a case of metabolic encephalopathy in a patient with life-threatening thyroid storm and bilateral frontal lobe lesions. Hypoglycemia may have been involved in the development of encephalopathy in our patient. Health care providers should consider thyroid storm in the differential diagnosis of hyperthermia, seizures, and coma. Early plasmapheresis, hemofiltration, and hemoperfusion can lower T4 levels and improve prognosis in patients with thyroid storm and encephalopathy.

[Adult-onset COVID-19-associated Fulminant Acute Encephalopathy with Elevated Cerebrospinal Fluid Interleukin-8: A Case Report].

A 26-year-old woman receiving immunosuppressive therapy for polymyositis was infected with COVID-19 (an omicron mutant strain) and presented with fever. On the second day after the onset, she was admitted to our hospital and developed status epilepticus. Brain magnetic resonance imaging on admission revealed abnormal symmetric hyperintensities in the bilateral putamen and around the dorsal horns of the lateral ventricle. Three days after admission, brain computed tomography revealed marked cerebral edema and herniation. The cerebrospinal fluid (CSF) cell count was normal, and the reverse transcription polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 was negative. Interleukin (IL)-2, 6, and 10 levels were within the normal range in both serum and CSF, whereas IL-8 levels in the CSF were markedly higher compared to serum levels. She had fulminant acute encephalopathy, suspected to be in the early stages of acute necrotizing encephalopathy (ANE). Steroid pulse therapy and intravenous infusions of remdesivir were ineffective, and the patient died of sepsis on the 26th day after admission. We demonstrated that ANE may occur even in patients infected with Omicron strains and speculated that the pathogenesis in this case might be associated with intrathecal IL-8 production by microglial activation.

Predicting factors for acute encephalopathy in febrile seizure children with SARS-CoV-2 omicron variant: a retrospective study.

BACKGROUND: SARS-CoV-2 posed a threat to children during the early phase of Omicron wave because many patients presented with febrile seizures. The study aimed to investigate predicting factors for acute encephalopathy of children infected by SARS-CoV-2 Omicron variant presenting with febrile seizures. METHODS: The retrospective study analyzed data from pediatric patients who visited the emergency department of Chang Gung Memorial Hospital in Taiwan between April and July 2022. We specifically focused on children with COVID-19 who presented with febrile seizures, collecting demographic, clinical, and laboratory data at the pediatric emergency department, as well as final discharge diagnoses. Subsequently, we conducted a comparative analysis of the clinical and laboratory characteristics between patients diagnosed with acute encephalopathy and those with other causes of febrile seizures. RESULTS: Overall, 10,878 children were included, of which 260 patients presented with febrile seizures. Among them, 116 individuals tested positive for SARS-CoV-2 and of them, 14 subsequently developed acute encephalopathy (12%). Those with acute encephalopathy displayed distinctive features, including older age (5.1 vs. 2.6 years old), longer fever duration preceding the first seizure (1.6 vs. 0.9 days), cluster seizure (50% vs. 16.7%), status epilepticus (50% vs. 13.7%) and occurrences of bradycardia (26.8% vs. 0%) and hypotension (14.3% vs. 0%) in the encephalopathy group. Besides, the laboratory findings in the encephalopathy group are characterized by hyperglycemia (mean (95% CI) 146 mg/dL (95% CI 109-157) vs. 108 mg/dL (95% CI 103-114) and metabolic acidosis (mean (95% CI) pH 7.29(95% CI 7.22-7.36) vs. 7.39 (95%CI 7.37-7.41)). CONCLUSIONS: In pediatric patients with COVID-19-related febrile seizures, the occurrence of seizures beyond the first day of fever, bradycardia, clustered seizures, status epilepticus, hyperglycemia, and metabolic acidosis should raise concerns about acute encephalitis/encephalopathy. However, the highest body temperature and the severity of leukocytosis or C-reactive protein levels were not associated with poor outcomes.

A Young Girl with Acute Encephalopathy Who Presented with Status Epilepticus Following a Flu-Like Illness.

BACKGROUND Acute necrotizing encephalopathy of childhood (ANEC) is a rare form of acute encephalopathy in children that is characterized by rapid and progressive deterioration in the patient's clinical condition. Our aim in reporting the case is to highlight the importance of early diagnoses and aggressive early management of ANEC to achieve a better outcome. We report the case of a 5-year-old girl who presented with acute progressive encephalopathy with bilateral symmetrical thalamic involvement and brainstem lesion proceeded by a flu-like illness. CASE REPORT We report a 5-year-old girl who was previously healthy. She presented with rapid progressive encephalopathy and status epilepticus following a flu-like illness. Her magnetic resonance imaging (MRI) showed significance symmetrical bilateral thalamic enhancement with brainstem lesions, which is consistent with the diagnosis of ANEC of childhood, and her initial electroencephalogram (EEG) showed severe encephalopathy. Despite extensive management of ANEC, the patient showed a poor prognosis. CONCLUSIONS ANEC is a rare, specific, devastating condition in the pediatric population. Early diagnosis and aggressive management should be initiated immediately to avoid the high mortality associated with the condition. Furthermore, to highlight the importance of the clear history of the patient who presented with rapid and progressive deterioration in the level of consciousness and status epilepticus proceeded by viral illness, a rapid neuroradiological images such as brain MRI should be obtained to confirm the diagnosis of this rare condition. We also seek to increase awareness of this disorder among healthcare workers and general practitioners.

A rare case of daratumumab-associated encephalopathy in multiple myeloma.

Aim: Daratumumab, a CD38 monoclonal antibody, has been widely used in patients with multiple myeloma. Although a variety of adverse events have been reported, consciousness impairment has not been reported yet. We report a case of encephalopathy associated with daratumumab. Case presentation: A 57-year-old male, diagnosed with relapsed multiple myeloma, was treated with daratumumab. He developed a loss of consciousness after the first administration. Cerebral spinal fluid and magnetic resonance imaging of the brain suggested encephalopathy. Conclusion: It is recommended to be aware of rare but life threatening side effects of daratumumab. We present a case of rare encephalopathy characterized by consciousness disorder associated with daratumumab, which was successfully resolved on prompt institution of steroids, although the mechanism was unknown.

Daratumumab is a drug. It is used to treat multiple myeloma. Many patients use this drug. It has many side effects. But consciousness disorder is rare. A 57-year-old male was diagnosed with multiple myeloma. He was treated with daratumumab. He became unconscious after this treatment. Steroids helped his recovery.

[A case of Hashimoto's encephalopathy with acute onset of psychiatric symptoms and diffuse deep white matter lesions on brain MRI].

A 51-year-old man developed acute disturbances in consciousness and psychiatric symptoms one month prior to admission. He was referred and admitted to the Department of Psychiatry of our hospital and transferred to the neurology department because diffuse white matter lesions were found on his brain during MRI. 123I-IMP-SPECT showed extensive cerebral hypoperfusion mainly in the frontal lobes. Anti-Tg, anti-TPO, and anti-NAE antibodies were positive. These findings led to a diagnosis of Hashimoto's encephalopathy. The patient responded to steroid pulse therapy, high-dose steroid therapy, and intravenous immunoglobulin therapy, showing improvement in symptoms and imaging findings. Hashimoto's encephalopathy often presents with MRI findings similar to those of limbic encephalitis, when the patient presents with acute consciousness disturbance and psychiatric symptoms. However, this case showed diffuse white matter lesions, which may be clinically important for the differential diagnosis.

Delayed encephalopathy after acute carbon monoxide poisoning: a case study.

Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is a relatively rare inflammatory-associated neurometabolic complication. In this article, we present a case report of a 50-year-old male patient with a history of carbon monoxide poisoning. This acute poisoning, although successfully controlled during a stay in the intensive care unit of a local hospital, later led to persistent neurological symptoms. The patient was then treated in the inpatient unit of the rehabilitation clinic, where cognitive deterioration began to develop 20 days after admission. Subsequent examination using EEG and magnetic resonance imaging confirmed severe encephalopathy later complicated by SARS-CoV-2 infection with fatal consequences due to bronchopneumonia. Because currently there are no approved guidelines for the management of DEACMP, we briefly discuss the existing challenges for future studies, especially the application of rational immunosuppressive therapy already in the acute treatment phase of CO poisoning, which could prevent the development of a severe form of DEACMP.

Transjugular intrahepatic portosystemic shunts for adults with hepatorenal syndrome.

BACKGROUND: Hepatorenal syndrome is a condition that occurs in people with chronic liver disease (such as alcoholic hepatitis, advanced cirrhosis, or fulminant liver failure) and portal hypertension. The prognosis is dismal, often with a survival of weeks to months. Hepatorenal syndrome is characterised by the development of intense splanchnic vasodilation favouring ascites and hypotension leading to renal vasoconstriction and acute renal failure. Therefore, treatment attempts focus on improving arterial pressure through the use of vasopressors, paracentesis, and increasing renal perfusion pressure. Several authors have reported that the placement of transjugular intrahepatic portosystemic shunts (TIPS) may be a therapeutic option because it decreases portal pressure and improves arterial and renal pressures. However, the evidence is not clearly documented and TIPS may cause adverse events. Accordingly, it is necessary to evaluate the evidence of the benefits and harms of TIPS to assess its value in people with hepatorenal syndrome. OBJECTIVES: To evaluate the benefits and harms of transjugular intrahepatic portosystemic shunts (TIPS) in adults with hepatorenal syndrome compared with sham, no intervention, conventional treatment, or other treatments. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 2 June 2023. SELECTION CRITERIA: We included only randomised clinical trials with a parallel-group design, which compared the TIPS placement with sham, no intervention, conventional therapy, or other therapies, in adults aged 18 years or older, regardless of sex or ethnicity, diagnosed with chronic liver disease and hepatorenal syndrome. We excluded trials of adults with kidney failure due to causes not related to hepatorenal syndrome, and we also excluded data from quasi-randomised, cross-over, and observational study designs as we did not design a separate search for such studies. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. all-cause mortality, 2. morbidity due to any cause, and 3. serious adverse events. Our secondary outcomes were 1. health-related quality of life, 2. non-serious adverse events, 3. participants who did not receive a liver transplant, 4. participants without improvement in kidney function, and 5. length of hospitalisation. We performed fixed-effect and random-effects meta-analyses using risk ratio (RR) or Peto odds ratio (Peto OR), with 95% confidence intervals (CI) for the dichotomous outcomes and mean difference (MD) or standardised mean difference (SMD) for the continuous outcomes. We used GRADE to assess certainty of evidence. MAIN RESULTS: We included two randomised clinical trials comparing TIPS placement (64 participants) versus conventional treatment (paracentesis plus albumin 8 g/L of removed ascites) (66 participants). The co-interventions used in the trials were dietary treatment (sodium less than 60 mmoL/day), spironolactone (300 mg/day to 400 mg/day), and furosemide (120 mg/day). Follow-up was up to 24 months. Both were multicentre trials from Spain and the USA, and Germany, conducted between 1993 and 2002. Most participants were men (aged 18 to 75 years). We are uncertain about the effect of TIPS placement compared with conventional treatment, during the first 24 months of follow-up, on all-cause mortality (RR 0.88, 95% CI 0.55 to 1.38; 2 trials, 130 participants; I2 = 58%; very low-certainty evidence) and on the development of any serious adverse event (RR 1.60, 95% CI 0.10 to 24.59; 2 trials, 130 participants; I2 = 78%; very low-certainty evidence). The use of TIPS may or may not result in a decrease in overall morbidity such as bacterial peritonitis, encephalopathy, or refractory ascites, during the first 24 months of follow-up, compared with the conventional treatment (RR 0.95, 95% CI 0.77 to 1.18; 2 trials, 130 participants; I2 = 0%; low-certainty evidence). We are uncertain about the effect of TIPS placement versus conventional treatment on the number of people who did not receive a liver transplant (RR 1.03, 95% CI 0.93 to 1.14; 2 trials, 130 participants; I2 = 0%; very low-certainty evidence) or on the length of hospitalisation (MD -20.0 days, 95% CI -39.92 to -0.08; 1 trial, 60 participants; very low-certainty evidence). Kidney function may improve in participants with TIPS placement (RR 0.53, 95% CI 0.27 to 1.02; 1 trial, 70 participants; low-certainty evidence). No trials reported health-related quality of life, non-serious adverse events, or number of participants with improvement in liver function associated with the TIPS placement. Funding No trials reported sources of commercial funding or conflicts of interest between researchers. Ongoing studies We found one ongoing trial comparing TIPS with conventional therapy (terlipressin plus albumin) and listed one study as awaiting classification as no full-text article could be found. AUTHORS' CONCLUSIONS: TIPS placement was compared with conventional treatment, with a follow-up of 24 months, in adults with hepatorenal syndrome type 2. Based on two trials with insufficient sample size and trial limitations, we assessed the overall certainty of evidence as low or very low. We are unsure if TIPS may decrease all-cause mortality, serious adverse events, the number of people who did not receive a liver transplant, and the days of hospitalisation because of the very low-certainty evidence. We are unsure if TIPS, compared with conventional treatment, has better effects on overall morbidity (bacterial peritonitis, encephalopathy, or refractory ascites). TIPS may improve kidney function, but the certainty of evidence is low. The trials included no data on health-related quality of life, non-serious adverse events, and liver function associated with the TIPS placement. We identified one ongoing trial and one study awaiting classification which may contribute to the review when information becomes available.

New onset of isolated adrenocorticotropin deficiency associated with encephalopathy following coronavirus disease 2019 in a healthy elderly man.

Coronavirus disease 2019 (COVID-19) due to a severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can include various systemic organ disorders including endocrinopathies and neurological manifestations. We report the case of a 65-year-old Japanese man who developed isolated adrenocorticotropic hormone (ACTH) deficiency and encephalopathy following SARS-CoV-2 infection. Two weeks after his COVID-19 diagnosis, he was emergently admitted to our hospital because of subacute-onset delirium. On admission, he presented hyponatremia (128 mEq/L) and secondary adrenal insufficiency (ACTH <1.5 pg/mL, cortisol 0.53 µg/dL). Brain imaging and laboratory examinations including SARS-CoV-2 polymerase chain reaction testing in the cerebrospinal fluid revealed no abnormalities. His consciousness level worsened despite the amelioration of hyponatremia by intravenous hydrocortisone (100 mg/day), but his neurological presentations completely resolved after three consecutive days of high-dose (400 mg/day) hydrocortisone. His encephalopathy did not deteriorate during hydrocortisone tapering. He continued 15 mg/day hydrocortisone after discharge. His encephalopathy might have developed via a disturbance of the autoimmune system, or a metabolic effect associated with adrenal insufficiency, although the time lag between the hyponatremia's improvement and the patient's neurological response to the steroid was incompatible with common cases of delirium concurrent with adrenal insufficiency. At 13 months after his hospitalization, the patient's neurological symptoms have not recurred and he has no endocrinological dysfunctions other than the remaining ACTH deficiency. A thorough consideration of the immunological and metabolic characteristics of SARS-CoV-2 is advisable when clinicians treat patients during and even after their COVID-19 disease period.

Progressive encephalopathy after routine 4-month immunizations in a patient with NAXD genetic variant.

Metabolic pathways are known to generate byproducts-some of which have no clear metabolic function and some of which are toxic. Nicotinamide adenine dinucleotide phosphate hydrate (NAD(P)HX) is a toxic metabolite that is produced by stressors such as a fever, infection, or physical stress. Nicotinamide adenine dinucleotide phosphate hydrate dehydratase (NAXD) and nicotinamide adenine dinucleotide phosphate hydrate epimerase (NAXE) are part of the nicotinamide repair system that function to break down this toxic metabolite. Deficiency of NAXD and NAXE interrupts the critical intracellular repair of NAD(P)HX and allows for its accumulation. Clinically, deficiency of NAXE manifests as progressive, early onset encephalopathy with brain edema and/or leukoencephalopathy (PEBEL) 1, while deficiency of NAXD manifests as PEBEL2. In this report, we describe a case of probable PEBEL2 in a patient with a variant of unknown significance (c.362C>T, p.121L) in the NAXD gene who presented after routine immunizations with significant skin findings and in the absence of fevers.

Clinical characteristics of SARS-CoV-2-associated encephalopathy in children: Nationwide epidemiological study.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sometimes triggers acute encephalopathy as a serious neurological complication in children. We previously reported the clinico-radiological findings of SARS-CoV-2-associated encephalopathy. The advent of the SARS-CoV-2 omicron variant led to a marked increase in pediatric patients with coronavirus disease 2019 (COVID-19); however, epidemiological changes with acute encephalopathy according to the emergence of SARS-CoV-2 have not yet been documented. Therefore, the present study investigated epidemiological differences in SARS-CoV-2-associated encephalopathy during the BA.1/BA.2 and BA.5 predominant periods and also between SARS-CoV-2-associated and non-SARS-CoV-2-associated encephalopathy. METHODS: We conducted a nationwide survey of SARS-CoV-2-associated encephalopathy in Japanese children between June and November 2022. We compared the present results during the BA.5 predominant period and previous findings during the BA.1/BA.2 predominant period. We also compared the clinico-radiological syndromes of encephalopathy between SARS-CoV-2-associated and non-SARS-CoV-2-associated encephalopathy. RESULTS: Although many patients with SARS-CoV-2-associated encephalopathy in the BA.5 predominant period had seizures as their initial symptoms, no significant differences were observed in the clinical features. Patients with SARS-CoV-2-associated encephalopathy had worse outcomes than those with non-SARS-CoV-2-associated encephalopathy (p-value = 0.003). Among 103 patients with SARS-CoV-2-associated encephalopathy, 14 (13.6%) had severe types of acute encephalopathy, namely, encephalopathy with acute fulminant cerebral edema (AFCE) and hemorrhagic shock and encephalopathy syndrome (HSES). Also, 28 (27.2%) patients with SARS-CoV-2-associated encephalopathy had poor outcome: severe neurological sequelae or death. Ninety-five patients (92.2%) were not vaccinated against SARS-CoV-2. CONCLUSIONS: In SARS-CoV-2-associated encephalopathy, high percentages of AFCE and HSES can result in poor outcomes.

Retinodural haemorrhage of infancy, abusive head trauma, shaken baby syndrome: The continuing quest for evidence.

The shaken baby syndrome was originally proposed in the 1970s without any formal scientific basis. Once data generated by scientific research was available, the hypothesis became controversial. There developed essentially two sides in the debate. One side claimed that the clinical triad of subdural haemorrhage, retinal haemorrhage, and encephalopathy, or its components, is evidence that an infant has been shaken. The other side stated this is not a scientifically valid proposal and that alternative causes, such as low falls and natural diseases, should be considered. The controversy continues, but the contours have shifted. During the last 15 years, research has shown that the triad is not sufficient to infer shaking or abuse and the shaking hypothesis does not meet the standards of evidence-based medicine. This raises the issue of whether it is fit for either clinical practice or for the courtroom; evidence presented to the courts must be unassailable. WHAT THIS PAPER ADDS: There is insufficient scientific evidence to assume that an infant with the triad of subdural haemorrhage (SDH), retinal haemorrhage, and encephalopathy must have been shaken. Biomechanical and animal studies have failed to support the hypothesis that shaking can cause SDH and retinal haemorrhage. Patterns of retinal haemorrhage cannot distinguish abuse. Retinal haemorrhages are commonly associated with extracerebral fluid collections (including SDH) but not with shaking. Infants can develop SDH, retinal haemorrhage, and encephalopathy from natural diseases and falls as low as 1 foot. The shaking hypothesis and the literature on which it depends do not meet the standards of evidence-based medicine.

The etiological spectrum of multiple ring-enhancing lesions of the brain: a systematic review of published cases and case series.

OBJECTIVE: Multiple ring-enhancing lesions of the brain are enigmatic neuroimaging abnormality. In this systematic review, we evaluated the etiological spectrum of these lesions. METHODS: This systematic review adhered to the PRISMA guidelines. We searched PubMed, Embase, Scopus, and Google Scholar up until 15 June 2023. We included case reports and case series. Quality evaluation of each case was based on selection, ascertainment, causality, and reporting. The extracted information included demographic characteristics, clinical features, type and number of multiple enhancing brain lesions, diagnostic procedures, final diagnoses, treatments, and patient outcomes. PROTOCOL REGISTRATION: PROSPERO CRD42023437081. RESULTS: We analyzed 156 records representing 161 patients, 60 of whom were immunocompromised. The mean age was 42.6 years, and 67% of patients experienced symptoms for up to 1 month. A higher proportion of immunocompromised patients (42% vs. 30%) exhibited encephalopathy. Chest or CT thorax abnormalities were reported in 27.3% of patients, while CSF abnormalities were found in 31.7%, more frequently among the immunocompromised. Definitive diagnoses were established via brain biopsy, aspiration, or autopsy in 60% of cases, and through CSF examination or other ancillary tests in 40% of cases. Immunocompromised patients had a higher incidence of Toxoplasma gondii infection and CNS lymphoma, while immunocompetent patients had a higher incidence of Mycobacterium tuberculosis infection and immune-mediated and demyelinating disorders. The improvement rate was 74% in immunocompetent patients compared to 52% in the immunocompromised group. CONCLUSION: Multiple ring-enhancing lesions of the brain in immunocompromised patients are more frequently caused by Toxoplasma gondii infections and CNS lymphoma. Conversely, among immunocompetent patients, Mycobacterium tuberculosis infection and immune-related demyelinating conditions are common.