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.

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.

Cerebrospinal fluid oligoclonal IgG bands in patients with spinal arteriovenous malformation and structural central nervous system lesions.

OBJECTIVE: To investigate the incidence and characteristics of patients with structural central nervous system (CNS) lesions and cerebrospinal fluid oligoclonal IgG bands. DESIGN: A retrospective study. METHOD: The medical records of patients with cerebrospinal fluid oligoclonal IgG bands were evaluated for the presence of structural CNS lesions, their location and cause, and for clinical characteristics. SETTING: Cerebrospinal fluid oligoclonal IgG bands were examined in the Neuroimmunology Laboratory, Hadassah University Hospital, Jerusalem, Israel. PATIENTS: Two hundred seventy of 570 patients with positive cerebrospinal fluid oligoclonal IgG bands were available for analysis. Twenty patients had structural CNS lesions. RESULTS: Twenty (7.5%) of the 270 patients had structural CNS lesions: 3 patients had spinal arteriovenous malformation; 5 patients had tumors; 9 patients had compressive cervical myelopathy. Traumatic leukomalacia, Arnold-Chiari malformation type 1, and CNS hemosiderosis were present in 1 patient each. In 2 patients (1 patient with recurrent meningioma and 1 patient with posttraumatic encephalomalacia) the presence of a structural CNS lesion was followed by the development of multiple sclerosis. In all 3 patients with spinal arteriovenous malformation, oligoclonal IgG identification prolonged the time to diagnosis and therapy, which varied from a few weeks to 3 years. CONCLUSIONS: Structural CNS lesions, responsible for the neurological disorder, were present in 20 patients (7.5%) with cerebrospinal fluid oligoclonal IgG bands. The mechanism underlying oligoclonal IgG presence in spinal arteriovenous malformation and the coexistence of multiple sclerosis and structural CNS lesions is unknown, but may be related to recurrent tissue damage with repeated presentation of CNS antigens to the immune system.

Polioencephalomalacia induced with amprolium in buffalo calves--clinicopathologic findings.

Polioencephalomalacia was induced in eight buffalo calves, 6-12 months old, by drenching amprolium (300 mg/kg body weight per day) for 29-55 days. Four buffalo calves of the same age group were drenched with tap water only and served as control. Blood samples were collected at different intervals during amprolium administration until the onset of clinical signs. Cerebrospinal fluid was also collected prior to amprolium administration and at the onset of clinical signs. A significant progressive decrease in erythrocyte transketolase (TK) activity and an increase in the percent of thiamine pyrophosphate (TPP) effect were observed in amprolium-fed calves during amprolium administration until the onset of clinical signs. There was a significant increase in blood lactate and blood pyruvate concentrations and a significant decrease in lactate/pyruvate ratio at the onset of clinical signs. Serum electrolyte (Na, Ca, P, Mg) concentrations showed no significant changes. However, the serum potassium concentration had decreased significantly at the onset of signs. The cerebrospinal fluid analyses revealed a significant increase in lactate and pyruvate concentrations and lactate/pyruvate ratio in amprolium-fed calves. The electrolytes (Na, K, Ca, P and Mg) of cerebrospinal fluid did not show any change. It is concluded that oral administration of amprolium (300 mg/kg body weight daily) for 4-6 weeks produces biochemical changes characteristic of polioencephalomalacia in buffalo calves.

[Topography and structure of secondary brain damage in edema associated with supratentorial foci of encephalomalacia]. / Topografia i struktura wtórnych uszkodzen mózgu w przebiegu obrzeku towarzyszacego nadnamiotowym ogniskom rozmiekania mózgu.

The paper comprises 70 cases of extensive supratentorial infarctions. The topography and structure of secondary lesions occurring in the region of herniation and displacements caused by the coexisting brain edema were analysed. The extent of edema served as criterion in the division of the material into three groups in dependence on the occurrence of herniations and displacements. Most frequent was herniation of hippocampal uncus and most rare that of the cerebellar vermis. In group I showing no herniations selective necrosis was noted of neurons particularly sensitive to ischemia and anoxia, especially in Sommer's sector of the hippocampus. In group II secondary necrosis was visible in the regions of herniae, and in the group III also in the translocated deep brain structures in the hemisphere contralateral to the infarct and in the brain stem where, moreover, secondary hemorrhages were present. Supratentorial secondary hemorrhages were less frequent. They were noted in the thalamus both on the side of the infarct and in the contralateral hemisphere. Supratentorial necroses were more frequent. Their intensity varied from selective necrosis to Jacob's edematous necrosis. Severe displacement of deep structures and of the brain stem was associated with development of secondary internal hydrocephalus, especially in the hemisphere contralateral to the herniation. To the most important pathogenetic factors causing development of secondary morphological lesions belong disturbances of blood supply occurring as the result of pressure differences between the supra- and infratentorial space, resulting from pressure and displacement of arterial vessels, damage of their walls and distrubances of venous flow and also development of secondary internal hydrocephalus. Extensive necroses and hemorrhages increase the area of primary necrosis. Lesions resulting from herniation, displacement and compression of vessels were superposed on the picture of brain edema both present or passed. Secondary necroses damaging bilaterally structures belonging to the limbic system and reticular formation may be an additional factor in the development of edematous encephalopathy and the development of a psychoorganic syndrome after stroke.

Characterization of experimentally induced equine leukoencephalomalacia (ELEM) in ponies (Equus caballus): preliminary report.

An isolate of Fusarium moniliforme (M-1225 Cairo #1) was cultured on autoclaved corn and fed daily to 5 ponies at a rate of 2.5 g corn/kg body wt. One pony developed clinical signs of toxicity after 28 days and was sacrificed. The remaining 4 ponies developed no clinical sign of toxicity even after extended exposure. Hematology, serum chemistry, cerebrospinal fluid (CSF), and liver and brain pathology were evaluated as possible diagnostic and prognostic indicators. Hematology was not informative. Aspartate aminotransferase and gamma-glutamyltranspeptidase activities were elevated only in the clinically positive pony. CSF was most informative. Elevated myelin basic protein levels (greater than 14 ng/ml; normal less than 2.0 ng/ml) and cytologic changes consistent with chronic inflammation were observed in the clinically positive pony. Chronic inflammation was also seen in one clinically normal pony. Cytoplasmic vacuolation and clumping were observed in the hepatocytes of all ponies. Brain pathology was consistent with ELEM in the clinically positive pony.

[Clinical course and CSF lactate in encephalomalacia (author's transl)]. / Uber die Korrelation von klinishcem Verlauf und Liquorlaktatspiegel bei enzephalomalazischen Insulten.

LCS level of lactate and clinical status correlate well during the initial stage of encephalomalacia (2nd-4th day) and during a period of 12 to 14 days after infarction LCS level of lactate may, therefore, be regarded as important parameter for short-term prognosis of encephalomalcia. The use of a semiquantitative clinical score also permits predictions as to the extent of remission to be expected. The reliability of this model of prognosis is limited by the comparatively small number of patients so far examined, the assumption of a linear relation between clinical alterations and changes in LCS lactate, as well as by the difficulty of determining LCS lactate in most severe cases at the specific time requested by the examination programme.