Hemorragic presentation of Listeria Monocytogenes rhombencephalic abscess.

Early diagnosis of cryptococcal meningoencephalitis in HIV-negative patients: Integration of brain MRI and clinical findings

57-Year-Old Woman With Fever and Confusion

IntroductionListeriosis is a severe food-borne disease caused by Listeria monocytogenes infection. The data of listeriosis in Xi’an population are limited. The aim of this study is to evaluate the clinical features and fatality risk factors for listeriosis in three tertiary-care hospitals in Xi’an, ChinaMethodsThe characteristics of demographic data, underlying diseases, clinical manifestations, laboratory indicators, cranial imaging examination, antibiotics therapeutic schemes, and clinical outcomes were collected between 2011 and 2023. Logistic regression analysis was performed.ResultsSeventy-one etiologically confirmed listeriosis patients were enrolled, including 12 neonatal and 59 non-neonatal cases. The majority of neonatal listeriosis presented as preterm (50%) and fetal distress (75%). The main clinical manifestations of non-neonatal listeriosis included fever (88%), headache (32%), disorder of consciousness (25%), vomiting (17%), abdominal pain (12%), and convulsions (8%). The fatality rate in neonatal cases was higher than in non-neonatal listeriosis (42 vs. 17%). Although no deaths were reported in maternal listeriosis, only two of 23 patients had an uneventful obstetrical outcome. Five maternal listeriosis delivered culture-positive neonates, three of whom decreased within 1 week post-gestation due to severe complications. Twenty-eight cases were neurolisteriosis and 43 cases were bacteremia. Neurolisteriosis had a higher fatality rate compared with bacteremia listeriosis (36 vs. 12%). The main neuroradiological images were cerebral edema/hydrocephalus, intracranial infection, and cerebral hernia. Listeria monocytogenes showed extremely low resistance to ampicillin (two isolates) and penicillin (one isolate). The fatality risk factors were the involvement of the central nervous system, hyperbilirubinemia, and hyponatremia for all enrolled subjects. Hyperuricemia contributed to the elevation of fatality risk in non-neonatal listeriosis.ConclusionsWhen the patients suffered with symptoms of fever and central nervous system infection, they should be alert to the possibility of listeriosis. Early administration of ampicillin- or penicillin-based therapy might be beneficial for recovery of listeriosis.

Objective To report the first case of central nervous system Whipple's disease (WD) with relatively good prognosis in China and present a brief review of central nervous system WD so as to improve the understanding of the diagnosis and treatment of this rare disease. Methods The clinical data of diagnosis, treatment and prognosis of one case of 35-year-old female was analysed in detail. Results Headache, hemiplesia and dementia were the main symptoms of this case and hypercranial pressure crisis occurred. During the course of disease, the patient successively presented paroxysmal extremity convulsion, right leg weakness, urinary incontinence, overeating, body mass increase. Despite of high dose of corticosteroid, penicillin and compound sulfamethoxazole were used, no effect was seen. Along with the increasing of intracranial pressure, cerebral hernia occurred. Cerebrospinal fluid examination indicated that glucose and chloride were normal while protein was obviously increased to 1700 mg/L. Electrocardiography (EEG) showed slow wave in right frontal and temporal lobes. Serial magnetic resonance imaging (MRI) revealed mutiple long T1 and long T2 signals mainly in right cerebral hemisphere, frontal parietal temporal lobes, semioval center and basal ganglion, with edema and irregular loose contrast and extended to left cerebral. Brain biopsy showed large pieces of necrosis at right fronto-temporal lobe with massive infiltration of lymphocytes and plasmocytes at perivascular and brain tissue, and exudation of glitter cells. Positive PAS and methenamine silver staining revealed bacterial particles inglitter cells. Central nervous system tumor, demyelinating disease and inflammatory pseudotumor were excluded. Both clinical symptoms and neuroimging recovered well after regular antibiotic therapy. Conclusion Central nervous system WD is a rare disease with complicated symptoms and imaging characters challenging diagnosis and treatment. The pathological findings may only indicate a special infection of central nervous system with unknown origin. The management is difficult. The misdiagnosis rate and fatality are high. It is important for clinicians to be aware of the features of this disease and make early decision to perform brain biopsy for diagnosis. Once it is diagnosed, normalized therapy should be given. DOI：10.3969/j.issn.1672-6731.2011.05.017

In recent years, there have been major advancements in management of infectious diseases; however, infections that affect the central nervous system (CNS) remain a significant challenge. They are often difficult to diagnose and treat, resulting in prolonged hospitalization and high morbidity and mortality rates. With modern-day travel, outbreaks of infections can rapidly transcend the globe. Not surprisingly, several recent movies, novels, and nonfiction books have been based on encephalitis, and outbreaks have received wide attention by the popular media. The book is has 51 chapters, which are organized thematically into 10 parts and presented in >900 pages. It is an exhaustive and authoritative clinical review that is written for the practicing and academic clinician. The first part has chapters on how to approach patients with suspected CNS infections, cerebrospinal fluid (CSF) findings, and neuroradiological changes. It also has broad chapters on meningitis and encephalitis. Forty of the 51 chapters are divided by organism and cover all viruses, bacteria, spirochetes, fungi, parasites, and prions. The book also has chapters on undiagnosed and noninfectious chronic meningitis, surgical and critical care management of CNS infections, and vaccines that are relevant to these infections. This combination of a syndromic approach to the diagnosis and management of CNS infections and division of chapters by microorganisms is a unique aspect of this book. Each chapter is divided into several sections that include the epidemiology or provide a historical perspective of the infection, a brief description about the organism, clinical features, diagnosis, and management. Each of these sections has multiple subheadings, making it easy to find and focus on areas of interest to the reader. Most chapters have multiple color illustrations, as well as photomicrographs showing the pathology or neuroradiological findings. Where appropriate, tables, figures, and algorithms for management have been included. Each chapter has been written by leaders in the field, and this expertise is clearly reflected in the detail and the clinical perspective provided in each of the chapters. For example, the chapter on poliomyelitis includes a magnetic resonance imaging (MRI) scan and pathological findings, which are probably very hard to obtain as the disease is so rare these days. In the part on viral pathogens and related disorders, the chapters on herpes viruses, rabies, and prion diseases are particularly noteworthy. They are very exhaustive with multiple illustrations describing the pathophysiology, MRI and pathological findings, and approach to treatment. The chapter on encephalitis provides a very detailed approach on how to establish an etiological diagnosis in these patients and covers all aspects of unique clinical manifestations, laboratory findings, MRI findings, and pathogen isolation, comparing each of these aspects in a set of several large tables. The chapter on bacterial meningitis is extensive in scope, nearly 55 pages in length. It covers usual and unusual organisms. The diagnostic utility and interpretation of CSF findings in circumstances such as a traumatic tap or partially treated meningitis is particularly useful and so is the discussion and recommendations for adjunctive therapy and use of corticosteroids. The chapter on neurosyphilis provides excellent algorithms for diagnosis in human immunodeficiency virus–infected and uninfected subjects. Several excellent chapters have been devoted to tropical infections such as cerebral malaria, cysticercosis and other parasitic infections, tuberculosis, tick-borne diseases, trypanosomiasis, and others. Overall, the book is very well written and an important resource for all clinicians who work with patients who may develop any kind of CNS infection.

Listeria monocytogenes (LM) infection induces pyroptosis, a form of regulated necrosis, in host macrophages via inflammasome activation. Here, we examined the role of Mint3 in macrophages, which promotes glycolysis via hypoxia-inducible factor-1 activation, during the initiation of pyroptosis following LM infection. Our results showed that Mint3-deficient mice were more resistant to lethal listeriosis than wild-type (WT) mice. Additionally, the mutant mice showed higher levels of IL-1β/IL-18 in the peritoneal fluid during LM infection than WT mice. Moreover, ablation of Mint3 markedly increased the activation of caspase-1, maturation of gasdermin D, and pyroptosis in macrophages infected with LM in vitro, suggesting that Mint3 depletion promotes pyroptosis. Further analyses revealed that Mint3 depletion upregulates inflammasome assembly preceding pyroptosis via glycolysis reduction and reactive oxygen species production. Pharmacological inhibition of glycolysis conferred resistance to listeriosis in a Mint3-dependent manner. Moreover, Mint3-deficient mice treated with the caspase-1 inhibitor VX-765 were as susceptible to LM infection as WT mice. Taken together, these results suggest that Mint3 depletion promotes pyroptosis in host macrophages, thereby preventing the spread of LM infection. Mint3 may serve as a target for treating severe listeriosis by inducing pyroptosis in LM-infected macrophages.

THU0036 Discriminating Central Nervous System Infection and Neuropsychiatric Involvement in Patients with Systemic Lupus Erythematosus: A Single-Center Experience

Listeria monocytogenes (LM) is a gram-positive intracellular bacillus that in immunodeficient patients, children, geriatric patients, pregnant women, and even in healthy individuals can cause central nervous system infection, bacteremia, and other clinical manifestations, becoming a relevant pathogen. From the Microbiology Service data of 'Gregorio Marañón' Hospital, we selected all positive biological sample cultures for LM from inflammatory bowel disease (IBD) patients, from January 1986 until January 2011. These cases were included in an SPSS database, analyzing several basal clinical characteristics and factors related to the infection. Three patients diagnosed with IBD had positive cultures for LM during this period. All of them were male, and also all of them had a diagnosis of Crohn's disease. Every patient had a corticosteroid cumulated dose of more than 400 mg (equivalency in methylprednisolone doses), adding anti-tumor necrosis factor-α treatment (certolizumab) in one patient. Prior colonoscopy with biopsy was performed in two patients. Clinical presentation of the infection was bacteremia in two patients, accompanied by central nervous system infection in one patient. One patient had isolated meningoencephalitis. Despite correct empiric treatment, one patient died from a cause related to the infection, that is, rombencephalitis. Increased incidence of LM bacteremia was found in IBD patients, compared with the general population (12.2 bacteremias/100 000 IBD patient-years, compared with 1.6 bacteremias/100 000 person-years), with an odds ratio of 7.4. IBD patients may be at risk for more frequent and serious LM infection compared with the general population.

Human parechovirus (HPeV), particularly genotype A3, is a recognized cause of sepsis-like illness and central nervous system (CNS) infection in neonates and young infants. Brain magnetic resonance imaging (MRI) plays a key role in identifying CNS involvement, although neuroradiological findings may be heterogeneous. We report two infants with PCR-confirmed HPeV CNS infection presenting at 10 and 40 days of life, respectively, with contrasting MRI patterns. The first neonate showed the typical phenotype of bilateral fronto-parietal and periventricular white matter diffusion restriction despite minimal cerebrospinal fluid (CSF) pleocytosis. The second infant demonstrated isolated diffuse leptomeningeal enhancement without parenchymal lesions. Both patients experienced rapid clinical recovery and remained seizure-free; neurodevelopment was normal at follow-up in the case with white matter involvement. These observations highlight the spectrum of MRI findings in early infant HPeV CNS infection and reinforce that normal or near-normal CSF parameters do not exclude significant CNS involvement. Early MRI, combined with molecular testing, may improve diagnostic accuracy and inform follow-up strategies.Conclusion: These observations highlight the spectrum of MRI findings in early infant HPeV CNS infection and reinforce that normal or near-normal CSF parameters do not exclude significant CNS involvement. Early MRI, combined with molecular testing, may improve diagnostic accuracy and inform follow up strategies. What is Known: • Human parechovirus (HPeV) CNS infection in young infants is commonly associated with white-matter diffusion abnormalities on MRI and minimal or absent CSF pleocytosis. • MRI is a key diagnostic tool in identifying CNS involvement, although neuroradiological findings may be heterogeneous. What is New: • This report describes two infants with HPeV CNS infection showing contrasting MRI patterns, including isolated leptomeningeal enhancement without parenchymal lesions. • These findings broaden the recognized neuroradiological spectrum of HPeV infection and highlight the diagnostic value of MRI even in clinically mild cases.Supplementary informationThe online version contains supplementary material available at 10.1007/s00431-026-06955-x.

BackgroundSeizures can be part of the clinical presentation of central nervous system (CNS) infections. We describe patients suspected of a neurological infection who present with a seizure and study diagnostic accuracy of clinical and laboratory features predictive of CNS infection in this population.MethodsWe analyzed all consecutive patients presenting with a seizure from two prospective Dutch cohort studies, in which patients were included who underwent cerebrospinal fluid (CSF) examination because of the suspicion of a CNS infection.ResultsOf 900 episodes of suspected CNS infection, 124 (14%) presented with a seizure. The median age in these 124 episodes was 60 years (IQR 45–71) and 53% of patients was female. CSF examination showed a leukocyte count ≥ 5/mm3 in 41% of episodes. A CNS infection was diagnosed in 27 of 124 episodes (22%), a CNS inflammatory disorder in 8 (6%) episodes, a systemic infection in 10 (8%), other neurological disease in 77 (62%) and in 2 (2%) episodes another systemic disease was diagnosed. Diagnostic accuracy of clinical and laboratory characteristics for the diagnosis of CNS infection in this population was low. CSF leukocyte count was the best predictor for CNS infection in patients with suspected CNS infection presenting with a seizure (area under the curve 0.94, [95% CI 0.88 – 1.00]).ConclusionsClinical and laboratory features fail to distinguish CNS infections from other causes of seizures in patients with a suspected CNS infection. CSF leukocyte count is the best predictor for the diagnosis of CNS infection in this population.

Listeriosis is highly prevalent in the animal farming industry, with Listeria monocytogenes as the causative pathogen. To identify potential therapeutic targets for LM infection, we investigated the mechanisms of LM infection in goat uteri. We inoculated a group of goats with LM via jugular vein injection, isolated and raised them, and subsequently collected sterile samples of their uterine tissue after they exhibited clinical symptoms of LM infection. We used Giemsa staining, immunohistochemical staining, real-time qPCR, and Western blotting as experimental methods.First, we investigated the mechanism of Listeria monocytogenes (LM) infection in the goat uterus by examining the expression levels of listeriolysin O, E-cadherin, and tyrosine kinase c-Met in the uterus.Furthermore, we investigated the impact of LM infection on uterine autophagy and cell apoptosis. The results indicate that the injection of LM into the goats' jugular veins leads to LM infection in the goats' uteri. During LM survival inside the goat uterine cells, there is a significant increase in the expression levels of LLO, E-cadherin, and c-Met in the host uterine tissue. This suggests that LM may potentially infect goat uteri through the InlA/E-cadherin and InlB/c-Met pathways. Furthermore, LM infection increases the levels of apoptosis and autophagy in goat uteri. Apoptosis genes Bcl-2 and Bax, as well as autophagy-related genes LC3B, PINK1, and Parkin, exhibit varying degrees of changes in localization and expression in goat uteri, mediating the occurrence of apoptotic and autophagic responses.

Progressive rash as the first sign of Listeria meningitis and bacteremia

Longitudinal multivoxel MR spectroscopy study of pediatric diffuse pontine gliomas treated by radiotherapy

Limited data exist on the role of adjunctive intraventricular (IVT) antibiotics for the treatment of central nervous system (CNS) infections in traumatic brain injury (TBI) patients. To evaluate differences in CNS infection cure rates for TBI patients who received adjunctive IVT antibiotics compared with intravenous (IV) antibiotics alone. We retrospectively identified patients with TBI and bacterial CNS infections admitted to the trauma intensive care unit (ICU) from 1997 to 2013. Study patients received IV and IVT antibiotics, and control patients received IV antibiotics alone. Clinical and microbiological cure rates were determined from patient records, in addition to ICU and hospital lengths of stay (LOSs), ventilator days, and hospital mortality. A total of 83 patients were enrolled (32 study and 51 control). The duration of IV antibiotics was similar in both groups (10 vs 12 days, P = 0.14), and the study group received IVT antibiotics for a median of 9 days. Microbiological cure rates were 84% and 82% in study and control groups, respectively (P = 0.95). Clinical cure rates were similar at all time points. No significant differences were seen in days of mechanical ventilation, ICU or hospital LOS, or hospital mortality. When only patients with external ventricular drains were compared, cure rates remained similar between groups. TBI patients with CNS infections had similar microbiological and clinical cure rates whether they were treated with adjunctive IVT antibiotics or IV antibiotics alone. Shorter than recommended durations of antibiotic therapy still resulted in acceptable cure rates and similar clinically relevant outcomes.

INTRODUCTION Mitochondrial DNA (mtDNA) is inherited maternally and codes for a mitochondrion's ribosomal proteins, tRNAs, and 13 of its respiratory chain proteins. mtDNA depletion occurs when mtDNA levels are quantitatively significantly decreased, usually with <1 residual molecule per mitochondrion (normal number of 2–10) (1). In a single cell normal and mutated mtDNA may coexist (ie, heteroplasmy). The threshold of mutated mtDNA for a deleterious phenotype is variable and mtDNA depletion is tissue specific. It may be expressed in a single organ or multiple organs, resulting in diverse clinical manifestations. In addition to liver failure in infancy (1), other clinical manifestations of mtDNA deletion syndrome (MDS) include myopathy or encephalomyopathy, lactic acidosis, heart failure, renal tubulopathy, and neurological abnormalities (2). Liver transplantation is a potential treatment option for end-stage liver disease from MDS. Contraindications to transplantation, including involvement of vital organs such as the brain, need to be actively investigated (3). The severity of extrahepatic involvement may be variable. Mild extrahepatic involvement may not be a contraindication to transplantation. We report on a child with liver failure from MDS with apparent neurodevelopmental progress who was referred for liver transplantation evaluation and found to have unique and new brain magnetic resonance imaging (MRI) findings not evident from a previous MRI study. CASE REPORT A 5-month-old Caucasian female patient of nonconsanguineous parents presented to our hospital with failure to thrive (poor weight gain over 2 months). Conception was assisted by the maternal use of clomiphene. She was born without any complications with a birth weight of 3.274 kg. She had neonatal jaundice at 2 weeks of age (total bilirubin, 195 mmol/L; conjugated bilirubin, 10 mmol/L), which spontaneously resolved. Her gross motor development at presentation was mildly delayed. She had a mild head lag, sat with support, rolled from back to front, transferred objects from hand to hand, and used a coarse ulnar grasp. She fixed and followed with her eyes, turned toward sounds, cooed, and smiled. Physical examination revealed an alert and interactive child. Her weight was less than the third percentile for age and her length and head circumference were at the 50th percentile for age. She was not obviously jaundiced with no scleral icterus. The liver was soft and palpated at 4 cm below the costal margin with no splenomegaly. She exhibited mild to moderate hypotonia. The rest of her examination findings were within normal limits. Initial investigations revealed a hemoglobin level of 123 g/L, platelet count of 381 × 109/L, white blood cell count of 11 × 109/L, albumin level of 44 g/L, alkaline phosphatase level of 160 U/L, aspartate aminotransferase level of 108 U/L, alanine aminotransferase level of 62 U/L, γ-glutamyl transpeptidase level of 290 U/L, total bilirubin level of 71 mmol/L, conjugated bilirubin level of 26 mmol/L, and International Normalized Ratio of 1.2. She had normal levels of creatinine, urea, sodium, potassium, chloride, glucose, lactate:pyruvate, pyruvate, α-1-antitrypsin, ferritin, and creatine kinase. Her bicarbonate level was low (17 mmol/L). She had elevated levels of ammonia (67 mmol/L), α-fetoprotein (79,220 kU/L), serum lactate (3.7 mmol/L), cerebrospinal fluid lactate (4.1 mmol/L), qualitative fecal fat (4+), anion gap (18), partial thromboplastin time (50), and alanine (1200 mmol/L). The remainder of her amino acid levels were normal. The ceruloplasmin level was low at 0.10 g/L, with normal levels of urinary copper. Other normal investigations included head computed tomography, MRI of the brain, auditory brainstem response, visual evoked potential, bone marrow aspirate, echocardiography, ophthalmology evaluation, sweat chloride test, oligosaccharide and mucopolysaccharide screen, acylcarnitine profile, very long chain fatty acid profile, and isoelectric focusing of serum transferrin. The results of the urine organic acids, amino acids, reducing substances, and succinylacetone evaluations were normal. Ultrasonography of the abdomen showed hepatomegaly with increased liver echogenicity. A liver biopsy performed at 6 months of age showed pale lobular hepatocytes, focal balloon hepatocytes, cholestasis, mild inflammation, and fibrosis. Electron microscopy confirmed the presence of small droplet lipid vacuoles in the cytoplasm with no definable mitochondrial abnormalities (Fig. 1). mtDNA quantification by polymerase chain reaction analysis conducted at Columbia University on the liver biopsy specimen revealed 85% mtDNA depletion, confirming the diagnosis of MDS. A skeletal muscle biopsy showed immature, infantile skeletal muscle correlating appropriately with hypotonia, focal perimysial infiltrate of macrophages likely secondary to prior injections, and no evidence of mitochondrial abnormalities. Respiratory enzyme analysis on muscle showed a slight reduction of complex IV, but normal complex IV-to-control ratio.FIG. 1: Uranyl acetate and lead citrate stained electron micrograph of a hepatocyte (original magnification × 15,000) shows steatosis (double arrows) and mitochondria (single arrow) with varied size and pale matrix.The medications used during the course of her illness included lansoprazole, pancrelipase, coenzyme Q10, L-carnitine, and ADEK pediatric multivitamin. She was maintained on nasogastric feeds of an elemental formula. Neurodevelopmental Course Our patient showed mild isolated gross motor delay at initial referral. At 8 months of age, she continued to show gross motor delay due to hypotonia with the inability to sit unsupported or maintain head control. At 11 months of age, progress included the ability to tripod sit, lift her head when prone, and use a pincer grasp. She also said "mama" appropriately, understood the word "no" and shook her head, responded to her name, laughed, played peek-a-boo, and displayed object permanence. She mouthed and explored toys orally with a preference of using her right hand. Her tone was difficult to assess due to irritability. No reflexes could be elicited in the lower extremities (concurrent vitamin E level of 9 μmol/L [normal, 5–20 μmol/L]). The remainder of her neurological examination findings were normal. She did not show any indications of developmental regression, seizures, abnormal trend of head circumference, or hearing or visual impairment during her course of illness. Feeding and Nutrition Course The patient continued to demonstrate poor weight gain (significantly less than the fifth percentile). At 11 months of age she received a gastrostomy tube for nutritional support and management of worsening gastroesophageal reflux. Gastroscopy showed marked thickening of the mucosa with edema of the fundus and body of the stomach, with biopsies demonstrating atrophy of antral and oxyntic mucosa and normal histology of the duodenum. Because of worsening regurgitation, she received a gastrojejunostomy tube at 12 months of age. Course of Liver and Neurologic Involvement The liver profile test results gradually worsened, and at 1 year of age showed an aspartate aminotransferase level of 537 U/L, alanine aminotransferase level of 239 U/L, alkaline phosphatase level of 334 U/L, γ-glutamyl transpeptidase level of 125 U/L, total bilirubin level of 174 mmol/L, conjugated bilirubin level of 102 mmol/L, International Normalized Ratio of 2.7, serum lactate level of 8.6 mmol/L, albumin level of 30 g/L, glucose level of 3.3 mmol/L, and ammonia level of 50 μmol/L. She also developed upper gastrointestinal bleeding, with endoscopy revealing mild grade I varices and portal hypertensive gastropathy with no active bleeding. Her liver function continued to deteriorate despite apparent neurodevelopmental progress and she was admitted to the hospital for liver transplantation evaluation. A repeat MRI of the brain performed as a routine part of liver transplantation evaluation showed T2 hyperintensities suggestive of leukoencephalopathy (Figs. 2,3). There was confluent involvement of the corona radiata of the cerebral hemispheres with extension to the subcortical U-fibers, external capsules, and extreme capsules. The T2 hyperintensities corresponded to diffusion abnormalities representing acute disruption of the sodium/potassium pumps in the white matter (ie, acute demyelination). The brain MRI findings posed a significant risk for poor neurological outcome. Therefore, she was declined as a candidate for liver transplantation. She developed subacute fulminant liver failure with encephalopathy, resulting in death 1 week later.FIG. 2: A T2 transverse image at the level of the basal ganglia shows increased T2 signal in the white matter of all lobes, including the external and extreme capsules.FIG. 3: A T2 transverse image at the level of the pons shows bilateral symmetric linear areas of increased signal (single arrows) in the dorsal brainstem, which extended into the medulla oblongata.An autopsy limited to the abdomen at the parents' request showed ascites and visceral congestion. The liver was enlarged and smooth with a glistening capsule. The parenchyma was homogenous, green, and greasy. There were occasional 0.1-cm nodules, which appeared to be fattier than the surrounding liver. Histological sections showed fibrous septae forming a nodular appearance with rare hepatocytes, marked bile duct proliferation, and cholestasis. The rare islands of preserved hepatic parenchyma showed moderate microvesicular steatosis. Respiratory chain enzyme analysis on liver tissue showed a significant decrease in complex IV activity. The dgK gene was sequenced and no mutation was found. A novel mutation in the MPV17 gene was detected; a mutation in the same gene was reported in 2 other families (4). Recently, her younger brother was diagnosed with MDS and also found to possess the same mutation in the MPV17 gene, but he remains well at age 17 months and has only mild liver disease. DISCUSSION We report on a child with subacute fulminant hepatic failure from MDS with a novel mutation in the MPV17 gene presenting with a clinical neurodevelopmental course that poorly correlated with her unique neuroimaging findings. Despite hypotonia and mild global developmental delay predominantly affecting gross motor skills, she showed progress in all areas of development. No regression or new neurological deficits were evident aside from areflexia of her lower limbs. However, the neuroimaging unexpectedly showed new and extensive neurological involvement with severe demyelination, increasing the risk of poor neurological outcome after liver transplantation. In the hepatic form of MDS, the onset of symptoms usually occurs in the first year of life (5). Clinical manifestations of liver disease are variable and include jaundice, hepatomegaly, hematemesis from rapidly progressive liver failure, hypoglycemia, and lactic acidosis (6,7). The genotype and phenotype correlation is poor, as shown by our case and her brother's having the same mutation yet different liver manifestations. The hepatic form of MDS is associated with a high mortality rate. Most patients die in early childhood, and 1 study reported death in all 10 patients with hepatic MDS (6). Liver transplantation is a potential treatment option for end-stage liver disease from MDS. A previous study of 6 children who received liver transplants for liver disease from mitochondrial disorders without extrahepatic manifestations reported that 5 children had positive outcomes, including survival of the perioperative period (3). Central nervous system (CNS) involvement is not uncommon in MDS. It may occur in isolation or in combination with hepatocerebral MDS. Previously described CNS involvement includes seizures with abnormal electroencephalogram discharges, encephalopathy, and abnormal imaging findings (1,8–17). In neuroimaging, cerebral atrophy is common (3,14–16). Signal intensity changes on MRI have been described as T2 hyperintensities in the putamina, corona radiata, and cerebral peduncles. Vu et al (14) described a patient with initial normal MRI findings at 9 months of age; repeat scanning for weakness, hypotonia, and hyporeflexia at 14 months showed incomplete myelination. Morris et al (17) described a patient with developmental regression and tremor with T2 hyperintensities in the putamina and brainstem; at pathological review, these lesions represented the sequela of a metabolic or toxic process rather than necrosis. Therefore, previous cases demonstrate progressive radiological disease associated with neurological decline. However, our patient showed neurodevelopmental gain, which did not parallel findings on MRI. Our patient had a normal MRI brain at 9 months of age. At 1 year of age, the MRI showed unique and widespread findings of signal abnormalities with T2 hyperintensities representing acute demyelination in the subcortical U-fibers, corona radiata of the cerebral hemispheres, external and extreme capsules, and dorsal aspect of the pons extending into the medulla oblongata. We recognize that the severity of CNS involvement in MDS is variable and may be progressive. It also may not be clinically evident. Determination of the extent of involvement is important due to the risk of persistent and possibly progressive CNS involvement. Dubern et al (3) recommend an emergency CNS evaluation by clinical examination for muscle weakness, hypotonia, and cerebellar ataxia; MRI of the brain; cerebrospinal lactate and protein measurements; and fundoscopy for pigmentary retinopathy. In addition, we recommend ongoing clinical neurodevelopmental examination conducted by a pediatric neurologist and serial brain MRI examinations. It is vital when considering liver transplantation for liver failure from MDS to proceed with caution and evaluate for extrahepatic involvement. The extent of neurological involvement is variable and may not be clinically evident; it is not always a contraindication to liver transplantation, but it may yield a serious risk for poor neurological outcome. In our patient repeat neurological imaging detected unique, new, and progressive neurological involvement that was not clinically evident or initially present. Thus, clinical and radiological findings need to be considered. In addition to clinical evaluation, we recommend serial neurological imaging studies for the evaluation of the extent and progression of CNS disease. Acknowledgments The authors thank Drs Salvatore DiMauro and Sara Shanske (Department of Neurology, Columbia College of Physicians and Surgeons, Columbia University, New York) and Dr M. Zeviani (Division of Molecular Neurogenetics, National Neurological Institute "C. Besta," Milan, Italy) for their work on the mtDNA analysis. The authors also thank Dr M. James Philips (Department of Paediatric Laboratory Medicine, Division of Pathology, Hospital for Sick Children, Toronto) for review of the liver biopsy specimen.