First case report of cerebral folate deficiency caused by a novel mutation of FOLR1 gene in a Chinese patient.

BACKGROUND: Cerebral folate deficiency (CFD) is a neurological disease, hallmarked by remarkable low concentrations of 5-methyltetrahydrofolic acid (5-MTHF) in cerebrospinal fluid (CSF). The primary causes of CFD include the presence of folate receptor (FR) autoantibodies, defects of FR encoding gene FOLR1, mitochondrial diseases and congenital abnormalities in folate metabolism. CASE PRESENTATION: Here we first present a Chinese male CFD patient whose seizure onset at 2 years old with convulsive status epilepticus. Magnetic Resonance Imaging (MRI) revealed the development of encephalomalacia, laminar necrosis in multiple lobes of the brain and cerebellar atrophy. Whole Exome Sequencing (WES) uncovered a homozygous missense variant of c.524G > T (p.C175F) in FOLR1 gene. Further laboratory tests demonstrated the extremely low level of 5-MTHF in the CSF from this patient, which was attributed to cerebral folate transport deficiency. Following the intravenous and oral treatment of calcium folinate, the concentrations of 5-MTHF in CSF were recovered to the normal range and seizure symptoms were relieved as well. CONCLUSIONS: One novel variation of FOLR1 was firstly identified from a Chinese male patient with tonic-clonic seizures, developmental delay, and ataxia. The WES and laboratory results elucidated the etiology of the symptoms. Clinical outcomes were improved by early diagnosis and proper treatment.

Consideration of evidence for therapeutic interventions in bovine polioencephalomalacia.

Randomized, masked, prospective clinical trial evidence for therapeutic intervention in naturally occurring bovine polioencephalomalacia (polio) is nonexistent. This article evaluates the use of thiamine and anti-inflammatories in the therapy of polioencephalomalacia based on available information related to the pathophysiology of the disease, induced models, disease outcome in other species (sheep), and parallels in similar disease in humans.

Severe enteroviral encephalitis complicated by encephalomalacia--case presentation.

Enteroviral encephalitis is a rare neuroinfection more often diagnosed in children within the context of enteroviral epidemic outbreaks. It has pleomorphic clinical features, variable severity and a definite potential to cause neuropsychological sequelae especially in infants. Some subtypes are extremely severe with a mortality rate of up to 25% by affecting the brain stem. These subtypes usually come with highly specific findings on neuroimaging. We present a paediatric case of diffuse encephalitis most likely enteroviral in nature, with some particular features concerning the severe clinical form, the neuroimaging aspects and the neuropsychological sequelae due to the rarely described evolution towards encephalomalacia.

Parkinsonism with multiple cysts in the bilateral striata.

The present paper reports on a 68-year-old man with a 10-year history of parkinsonism who developed hallucinations and delusions after admission to an intensive care unit for the treatment of organophosphate intoxication. His initial diagnosis was delirium. On the basis of brain computed tomography findings and clinical symptoms, we diagnosed drug-induced psychosis in parkinsonism with multiple cysts in the bilateral striata.

Effects of high-sulfur water and clinoptilolite on health and growth performance of steers fed forage-based diets.

Sulfur-induced polioencephalomalacia (sPEM), a neurological disorder affecting ruminants, is associated with consumption of diets with increased S (high-S). High-S water is commonly found in many western states and is a major source of dietary S for grazing cattle. Consumption of high-S water has been associated with sPEM and decreased performance. Identification of a feed supplement that would counteract the negative effects of high-S water would decrease the incidence of sPEM and prevent performance reductions in regions with problematic water sources. The objectives of this study were to 1) determine the effects of administering high-S drinking water to forage-fed feedlot steers on health and performance, and 2) determine the effectiveness of clinoptilolite, a clay mineral with increased cation-exchange capacity, in negating the effects of high-S drinking water. Yearling steers (n = 96; 318.2 +/- 2.1 kg of BW) were randomly assigned to 1 of 4 treatments for a 77-d trial period: control with low-S water (566 mg of SO(4)/L), high-S water (3,651 mg of SO(4)/L), or high-S water plus clinoptilolite supplemented at 2.5 or 5.0% of the diet DM. Feed and water consumption were measured daily, and all steers were weighed on d -2, -1, 29, 53, 76, and 77. Plasma samples were collected on d 0, 58, and 77, and liver samples on d 0 and 77. There was a greater (P or= 0.546) in ADG or G:F were observed. Plasma Cu decreased (P = 0.029) to a greater magnitude in high-S water steers than the control steers over the 77-d trial period. Mineral analyses of hepatic tissue from randomly selected healthy steers from each treatment group (n = 10 per treatment) showed an interaction (P

Persistence of herpes simplex virus DNA in cerebrospinal fluid of neonates with herpes simplex virus encephalitis.

OBJECTIVE: The significance of detecting herpes simplex virus (HSV) DNA in the cerebrospinal fluid (CSF) of infants with HSV encephalitis after receipt of prolonged therapy with high-dose (60 mg kg(-1) day(-1)) acyclovir is unknown. We report the clinical and laboratory characteristics, neuroimaging studies and outcomes of four neonates with HSV encephalitis who had persistence of CSF HSV DNA, by polymerase chain reaction (PCR) after 15 to 21 days of high-dose acyclovir therapy. STUDY DESIGN: Retrospective chart review. RESULTS: All four infants had abnormal neuroimaging studies and subsequently experienced severe developmental delay or death. CONCLUSION: A persistently positive CSF HSV PCR in neonates may be another risk factor for worse neurodevelopmental outcome. Prospective studies are needed to document how often HSV DNA persists in CSF, elucidate whether it represents an initially high CSF viral load, ongoing viral replication or viral resistance, and determine its possible association with neurodevelopmental impairment.

Hyperprolactinemia presenting with encephalomalacia-associated seizure disorder and infertility: a novel application for bromocriptine therapy in reproductive endocrinology.

OBJECTIVES: To describe successful oral bromocriptine therapy for hyperprolactinemia accompanied by seizure disorder and encephalomalacia identified during infertility evaluation. MATERIALS & METHODS: A 32 year-old male with an unspecified seizure disorder was referred for infertility consultation. The initial seizure was at age 12, and was treated sequentially with phenytoin, phenobarbitol, and carbamazepine monotherapy which was maintained for six years and then discontinued. At age 26, a second seizure was experienced and 150mg lamotrigine b.i.d. was initiated. When the patient married it was discovered that erection was impossible; tadalafil was administered without success. At our center, total testosterone was low at 107ng/dl and semen analysis revealed oligoasthenozoospermia. Serum prolactin was 79.3ng/ml; visual field examination was normal. Brain MR showed no pituitary enlargement. However, encephalomalacia of the right occiptal lobe with porencephalic dilation of the occipital horn of the right lateral ventricle was present. RESULTS: The patient was initially placed on 2.5mg/d bromocriptine but after three months only a nominal reduction of serum prolactin was achieved. Serum prolactin normalized (25.4ng/ml) after bromocriptine was increased to 7.5mg/d. Repeat semen analysis showed overall sperm concentration of 85M/ml, 30% motility and 12% normal forms morphology (Kruger strict criteria). Total testosterone level was 191ng/dl after final bromocriptine dose was attained, which was well tolerated. DISCUSSION: Bromocriptine has an established role in the management of hyperprolactinemia, particularly in women. For males with elevated serum prolactin even when associated with focal encephalomalacia and seizure disorder, bromocriptine therapy can offer safe benefits including improved semen parameters and normal serum testosterone levels.

[Severe late-onset group B streptococcal infection. A case report]. / Schwerer Verlauf einer "Late-Onset" B-Streptokokken Infektion - Ein Fallbericht -

BACKGROUND: Group B Streptococcus (GBS) is a well-known cause of neonatal pneumonia, sepsis and meningitis. Peripartal antibiotic prophylaxis for early-onset GBS infection is in routine use since the beginning of the last decade, but strategies for effective prevention of late-onset GBS infections are still lacking. CASE REPORT: Few hours after discharge from a non-local maternity ward a 3-week-old boy was admitted to our hospital because of GBS meningitis with necrotizing encephalomalacia. Maternal mastitis, not a disease of the baby, had led to the first admission. DISCUSSION: Case history and negative maternal swabs and cultures for GBS led to the hypothesis of nosocomial infection. Screening and risk based peripartal antibiotic prophylaxis, better monitoring and improved therapeutic modalities have reduced the incidence and mortality of early-onset GBS infections, but peripartal prophylaxis failed to influence late-onset GBS infections. Up to 40 % of infants with late-onset meningitis develop neurological sequelae. Maternal vaccination with multivalent conjugate vaccines against GBS is a new strategy which may lead to passive protection of the infant. Further studies to examine the efficacy of vaccines are in progress.

Polioencefalomalacia em bovinos nos estados de Mato Grosso do Sul e Säo Paulo / Polioencephalomalacia in cattle in the states of Mato Grosso do Sul and Säo Paulo

Trinta focos de polioencefalomalacia (PEM) foram diagnosticados no período de agosto de 1993 a outubro de 1997. Vinte e nove focos ocorreram no estado de Mato Grosso do Sul (MS) e um no estado de São Paulo (SP). Foram afetados bovinos de 4 a 84 meses de idade. A morbidade dos rebanhos afetados variou de 0,02% a 14,28% e a letalidade de 42,5% a 100%. A doença não apresentou uma sazonalidade e ocorreu em vários municípios do MS. Em todos os focos estudados os animais afetados eram criados em regimes de criação extensiva, com exceção de um foco. Os sinais clínicos observados foram exclusivamente nervosos e a evolução dos casos variou de 12 horas a 4 dias. A maioria dos animais tratados com tiamina e dexametasona recuperou-se. Histologicamente, as lesões consistiam de necrose laminar do córtex cerebral. Adicionalmente em 2 casos observaram-se hemorragias submeningeanas e corticais, e em 9 casos presença de infiltrado de eosinófilos. A dosagem de sódio no líquor apresentou-se elevada em um caso. A etiologia da PEM não está esclarecida, porém em alguns casos a intoxicação por cloreto de sódio/privação de água pode estar envolvida na etiologia da enfermidade. A PEM representa 4,78% dos casos de enfermidades de bovinos diagnosticadas no Laboratório de Anatomia Patológica da UFMS. Com bases nos resultados, verifica-se a importância da enfermidade no diagnóstico diferencial de outras doenças com quadro clínico neurológico no MS, principalmente a raiva, a meningoencefalite por herpesvírus bovino tipo 5 (HVB-5) e o botulismo.

Focal symmetrical encephalomalacia in a 6-month-old Dorset sheep.

Neurological examination of a sheep that had acute onset of recumbency and mental depression indicated a diffuse symmetrical thalamocortical lesion. Cerebrospinal fluid analysis suggested a degenerative central nervous system disease. Thiamin administration resulted in partial and temporary improvement. Brain histological lesions were typical of focal symmetrical encephalomalacia.

Sulphur-induced polioencephalomalacia in lambs.

An outbreak of polioencephalomalacia affected 16 of 46 Swaledale lambs and five of 25 Scottish blackface lambs 15 to 32 days after they were introduced to an ad libitum concentrate ration containing 0.43 per cent sulphur. The clinical signs were acute and included depression central blindness and head-pressing, but no hyperaesthesia, nystagmus, dorsiflexion of the neck or opisthotonos were observed. Treatment of the affected lambs with vitamin B1, dexamethasone and antibiotics was associated with a prolonged recovery period, though no further cases were identified after vitamin B1 had been given parenterally to all the lambs at risk.

A herd outbreak of equine leukoencephalomalacia.

Equine leukoencephalomalacia (ELEM) affected 6 of 10 pleasure horses in adjacent paddocks at a boarding facility. Four of the 6 affected horses died or were euthanized. Two of 3 horses presented for treatment survived with complete resolution of clinical signs. Treatment was primarily supportive. Dimethyl sulfoxide, dexamethasone, flunixin meglumine and thiamine were administered as anti-inflammatory agents and to decrease or prevent cerebral edema. Fusarium monileforme was cultured from ear corn fed the affected horses. Fumonisin B1, B2 and B3 were isolated.

Role of thiamine status in sulphur induced polioencephalomalacia in sheep.

The effects of excess dietary sulphur were studied in sheep supplemented and unsupplemented with thiamine. The diets contained either 0.19 per cent sulphur (LS) or 0.63 per cent sulphur (HS) in combinations with 14 mg kg-1 thiamine (LB1) or 243 mg kg-1 thiamine (HB1). A total of 56 two-month-old lambs were used. Groups consisting of nine, nine, 22 and 16 lambs were fed LS-LB1, LS-HB1, HS-LB1 and HS-HB1 diets, respectively for 14 weeks. Out of 22 lambs fed the HS-LB1 diet, seven lambs developed neurological signs between the third and eighth week of the trial. Two of these lambs died, three that were in extremis were euthanased, and two recovered completely. All clinically affected animals had extensive malacic lesions in the cerebral cortex, midbrain and brainstem. None of the lambs from the LS groups or HS-HB1 group developed clinical signs. Several clinically normal lambs from the HS-LB1 group had necrotic lesions in their brains at gross and microscopic examination. Supplementation with dietary thiamine prevented development of clinical signs, but did not totally prevent development of microscopic brain lesions. Brain thiamine concentration, transketolase activity and thiamine pyrophosphate (TPP) effect were not different (P greater than 0.05) among groups. There was a strong effect (P less than 0.0001) of dietary thiamine supplementation on blood thiamine concentration and TPP effect. Blood thiamine concentration was higher whereas TPP effect was lower in the thiamine supplemented sheep. Blood and tissue thiamine concentrations in sheep exposed to high dietary sulphur did not indicate either systemic or local thiamine deficiency per se. Increased TPP effect in sheep fed the HS-LB1 diet indicated mild to moderate metabolic thiamine deficiency. Thiamine inadequacy may be an effect of an increased requirement for thiamine in animals exposed to excess dietary sulphur.

[E-vitamin activity of vitamin E derivatives with experimental encephalomalacia in chicks]. / E-vitaminnaia aktivnost' proizvodnykh vitamina E pri eksperimental'noi entsefalomaliatsii u tsypliat.

When adding pharmacopoeian alpha-tocopherylacetate, short-chain alpha-tocopherylacetate, alpha-tocopherylquinine, short-chain alpha-tocopherylquinone and alpha-tocopheronolactone to E-avitaminotic rations pharmacopoeian alpha-tocopherylacetate and alpha-tocopheronolactone manifest the highest E-vitamin activity in preventing encephalomalacia in chickens. The action of alpha-tocopheronolactone is not directly associated with changes in the content of vitamin E and ubiquinone in the brain and liver tissues. All the studied derivatives are effective in increasing resistance of erythrocytes to osmotic hemolysis. The data obtained evidence for a nonspecific function of vitamin E in preventing alimentary encephalomalacia in chickens as well as for the absence of disturbances in ubiquinone metabolism under conditions of the E-hypovitaminosis experimental model.