Cortical spreading depression and central pain networks in trigeminal nuclei modulation: time for an integrated migraine pathogenesis perspective

Deficiency of vitamin K predisposes to early, classic or late hemorrhagic disease of the newborn (HDN); of which late HDN may be associated with serious and life-threatening intracranial hemorrhage. Late HDN is characterized intracranial bleeding in infants aged 1 week to 6 months due to severe vitamin K deficiency. Late HDN is still an important cause of mortality and morbidity in developing countries where vitamin K prophylaxis is not routinely practiced. Children with cholestatic liver disease are at risk for developing secondary vitamin K deficiency because of fat malabsorbtion and inadequate dietary intake. In this study, we described 11 infants with cholestatic liver disease with different etiologies exhibiting intracranial hemorrhage (ICH). Six patients underwent surgical evacuation of ICH, following the administration of vitamin K and/or fresh frozen plasma. The possibility of cholestatic liver disease should be considered in the treatment of ICH due to vitamin K deficiency.     

Benign intracranial hypertension in an older child with cystic fibrosis

Despite having normal height and weight, a 6-year-old girl had frequent bowel movements and slight recurrent chest infections since the age of 4 years and headache for 1 year. The patient appeared healthy, but examination of the ocular fundus revealed papilledema. Cranial computed tomography appeared normal. Lumbar puncture disclosed an elevated opening cerebrospinal fluid pressure, with normal biochemical, cellular, and bacteriologic findings. Laboratory investigations indicated pathologic steatorrhea, elevated electrolytes in 3 sweat tests, and low serum levels of vitamins A and E. The diagnosis of pseudotumor cerebri in a patient with cystic fibrosis was made. After treatment with prednisone (1 mg/kg/day), pancreatic extracts, and vitamin supplements, headache and papilledema resolved and serum vitamin A and E levels subsequently became normal. Older children with cystic fibrosis rarely have benign intracranial hypertension, but when present it is often due to hypervitaminosis during correction of malnutrition. In this child, pseudotumor cerebri and associated hypovitaminosis improved after combined corticosteroid and vitamin treatment.     

Reversible visual evoked potential abnormalities in vitamin E deficiency

A patient with cystic fibrosis and cirrhosis developed a progressive neurological syndrome associated with ataxia, proximal weakness, and ophthalmoplegia. Profound deficiencies of vitamins A, D, and E were present. Visual acuity and results of retinal funduscopy were normal. The pattern reversal visual evoked potential was initially abnormal (P100 latency, 136 and 130 ms from left and right eyes, respectively) but became normal (less than 3 standard deviations from mean control P100 latency) over a two-month period when vitamin E was administered. This case documents a potentially reversible visual evoked potential abnormality in a visually asymptomatic patient with vitamin E deficiency.     

迟发性维生素K缺乏并颅内出血临床分析

目的 探讨维生素K缺乏症并颅内出血误诊原因、诊断、手术治疗及其预后。方法 回顾性分析我院自1994年1月至2002年收治的维生素K缺乏症并颅内出血患儿48例。结果 本组48例，临床治愈27例，好转10例，放弃治疗3例，死亡8例；其中18例手术中，15例治愈，2例好转，1例死亡。结论 迟发性维生素K缺乏并颅内出血，见于新生儿和婴儿，发病突然，部分病例有前驱感染和使用抗生素的病史，易于误诊。CT检查、PT检验和维生素K治疗可有效确诊。对有手术指征，手术治疗可以提高治愈率，降低死亡率，改善生存质量。     

Intracranial hemorrhage in an infant due to vitamin K deficiency --successful management of spontaneous intracerebral and subjural hematoma]

A one-month-old male infant with spontaneous intracerebral and subdural hematomas due to vitamin K deficiency was described. He was breastfed. Loose stools continued and began to contain blood. He had fever, vomiting and convulsion, and became drowsy. The blood studies showed anemia and hypoprothrombinemia. Left carotid angiograms revealed intracerebral and subdural hematomas. He was treated successfully by immediate operation and administration of vitamin K. 2) Vitamin K deficient hemorrhage beyond the immediate newborn period was discussed with reference in the literature. Three etiologic factors included, decreased vitamin K intake, decreased intestinal absorption of vitamin K and decreased production of vitamin K by colon bacteria. The most important factor of the three seemed to be low vitamin K intake. Intracranial hemorrhage was recognized in about one third of the cases in the literature. It was emphasized that vitamin K deficiency occurring beyond the immediate newborn period was very important as a cause of intracranial hemorrhage in infancy.     

B超引导下婴儿晚发性维生素K缺乏颅内血肿的外科治疗

目的 探讨婴儿晚发性维生素K缺乏所致颅内出血的诊断及外科治疗。方法 对31例婴儿晚发性维生素K缺乏症致颅内出血的患儿进行手术治疗．其中12例侧脑室穿刺外引流术应用了经前囟头颅B超立体定向引导技术。结果 治愈26例．好转3例，死亡2例。结论 对本病有手术指征患儿及时手术，可明显降低病死率及致残率。应用头颅B超立体定向引导技术，使侧脑室穿刺更准确。     

Ataxia with isolated vitamin E deficiency presenting as mutation negative Friedreich's ataxia

Ataxia with vitamin E deficiency is an autosomal recessivecondition associated with a defect in the α-tocopherol transfer protein. Clinically it manifests as a progressive ataxia with aphenotype resembling that of Friedreich's ataxia. There is some evidence that progression of neurological symptoms is prevented byvitamin E therapy. A patient is described who was given a clinical diagnosis of Friedreich's ataxia. Molecular genetic analysis showed the absence of the frataxin gene expansion. Subsequent vitamin E assayshowed deficiency and a diagnosis of ataxia with vitamin E deficiencywas made. It is recommended that all patients with ataxia of unknowncause should have vitamin E deficiency excluded. When a diagnosis ofFriedreich's ataxia is considered patients should have frataxinanalysis in addition. Further, neurologists should be aware thatataxia with vitamin E deficiency may present as "mutationnegative" Friedreich's ataxia.

     

Facial palsy and idiopathic intracranial hypertension in twins with cystic fibrosis and hypovitaminosis A

Facial nerve palsies are uncommon in infants. We report on 10-week-old monozygotic twins, diagnosed with cystic fibrosis by newborn screening, who developed facial palsy and increased intracranial pressure. Cranial imaging and cerebrospinal fluid analysis produced normal results. Levels of serum vitamin A were below normal range. Low levels of vitamin A are associated with facial nerve paralysis, and are at least partly implicated in the development of increased intracranial pressure in infants with cystic fibrosis.     

Kupfermangel – eine behandelbare Ursache der Myelopathie

Copper deficiency myelopathy is an important and treatable differential diagnosis of vitamin B12 deficiency, of degenerative diseases presenting with the cardinal sign ataxia, and less often of motor neuron diseases. We report a 30-year-old female who presented with progressive gait disorder and sensory disturbances in her feet. Neurological examination showed tetraparesis with spastic ataxia. Laboratory investigations showed malabsorption, anemia, and leukopenia. Further extensive diagnostic investigations revealed copper deficiency due to malabsorption as the probable cause of the neurological deterioration. After oral copper substitution was started, the progression of her neurological symptoms could be stopped.     

Visual and somatosensory evoked potentials in vitamin E deficiency with cystic fibrosis

Patients with cystic fibrosis (CF) and pancreatic malabsorption frequently have vitamin E deficiency. Affected patients may develop spinocerebellar degeneration with dysarthria, ataxia, proximal weakness, proprioceptive loss and areflexia. Of a highly selected group of 10 patients with vitamin E levels below 5 micrograms/ml (normal 5-20 micrograms/ml), 7 had abnormal neurological examinations, predominantly affecting vibration and joint position perception with some severely affected patients manifesting diminished visual acuity, tremor, ataxia and diffuse weakness. Evoked potential studies showed marked abnormalities in 3 patients, demonstrating deficits in the optic pathways and in the cervical cord dorsal column pathways. Evoked potential studies may supplement careful neurological examination in patients with CF before and after supplementation with vitamin E to evaluate their progression and response to treatment.     

Vitamin K deficiency in severely disabled children

Vitamin K status was examined in 21 severely disabled children in our hospital from September 2001 to August 2002, and 9 children were found to have a vitamin K deficiency. The 21 patients were divided into two groups: group A, 9 patients with vitamin K deficiency, and group B, 12 patients without vitamin K deficiency. The laboratory data and background factors in the two groups were compared statistically. In group A, all patients received enteral nutrition and anticonvulsants. The protein induced by vitamin K absence-II values were elevated in eight patients. Seven exhibited a bleeding tendency. Six developed vitamin K deficiency in association with infection and four were treated with antibiotics. All showed a good response to the administration of vitamin K. The patients in group A had factors such as use of antibiotics, infection, and elemental nutrition at significantly higher rates than those in group B. Data indicating nutrition factors such as body weight, caloric intake, total protein level, and hemoglobin level were not significantly different between the two groups. Severely disabled children suffer from deficiencies of various nutritional elements. However, vitamin K deficiency in severely disabled children has not been fully investigated. Infection, use of antibiotics, and elemental nutrition are risk factors for vitamin K deficiency in severely disabled children. In severely disabled children, there might be marginal vitamin K intake via enteral nutrition, so more vitamin K supplementation is necessary, especially with infection and use of antibiotics.     

Rise in Late Onset Vitamin K Deficiency Bleeding in Young Infants Because of Omission or Refusal of Prophylaxis at Birth

BackgroundNewborns are at risk for vitamin K deficiency and subsequent bleeding unless supplemented at birth. Vitamin K deficiency bleeding is an acquired coagulopathy in newborn infants because of accumulation of inactive vitamin K–dependent coagulation factors, which leads to an increased bleeding tendency. Supplementation of vitamin K at birth has been recommended in the United States since 1961 and successfully reduced the risk of major bleeding. Refusal or omission of vitamin K prophylaxis is increasing and puts newborn infants at risk for life-threatening bleeding.PatientsOver an eight month period, we encountered seven infants with confirmed vitamin K deficiency; five of these patients developed vitamin K deficiency bleeding.ResultsThe mean age of the seven infants with vitamin K deficiency was 10.3 weeks (range, 7-20 weeks); manifestations ranged from overt bleeding to vomiting, poor feeding, and lethargy. None of the infants had received vitamin K at birth, and all were found to have profound derangement of coagulation parameters, which corrected rapidly with administration of vitamin K in IV or intramuscular form. Four of the seven infants had intracranial hemorrhage; two of these infants required urgent neurosurgical intervention.ConclusionSupplementation of vitamin K at birth for all newborns prevents major hemorrhagic complications, such as intracranial bleeding, due to vitamin K deficiency. Parental refusal of vitamin K is increasingly common. It is critical that health care providers and the public be made aware of the varied presentation of this preventable acquired coagulopathy.     

A study of the relationship between neurological function and serum vitamin E concentrations in patients with cystic fibrosis.

A patient with cystic fibrosis and undetectable serum vitamin E concentrations is described who developed a progressive spinocerebellar syndrome and pigmentary retinopathy with abnormal somatosensory and visual evoked potentials (SSEPs and VEPs). In order to assess the relationship between neurological function and serum vitamin E concentrations in cystic fibrosis, 29 unselected patients who had no neurological symptoms were examined neurologically. Ten were randomly selected for neurophysiological assessment by recording SSEPs and VEPs. Electroretinograms (ERGs) were also performed in five cases. The findings were correlated with serum vitamin E concentrations which were unknown to the neurological investigators prior to completion of the study. Only one patient had definite reflex and sensory abnormalities, and the remaining 28 were clinically normal. The ERG was abnormal in two cases, one of whom had abnormal VEPs. SSEPs were normal in all 10 cases. Twenty six patients had serum vitamin E concentrations below the normal range. In two of the three patients who had definite neurological or electrophysiological abnormalities serum vitamin E concentrations were below the median value for the whole group.     

An unusual case of Munchausen syndrome by proxy

An 11-year-old boy was presented by his father with a long and plausible history of cystic fibrosis. The diagnostic test for cystic fibrosis, the sweat test, was normal and excluded the diagnosis. The medical history was later found to be false, and the child to be well. By definition, the case met the criteria for Munchausen Syndrome by Proxy with fabrication of symptoms on behalf of another in order to deceive medical personnel. Unusual features included the illness chosen, the father as the parent falsifying illness, his failure to pursue unnecessary investigations and treatment, and the ease with which he relinquished the diagnosis of cystic fibrosis.     

婴儿维生素K缺乏致颅内出血36例临床分析

目的 探讨婴儿维生素K缺乏致颅内出血的l临床特点、远期预后随访和预防. 方法收集新华医院小儿神经外科自2000年11月至2007年9月收治的36例维生素K缺乏致颅内出血患儿的病史资料,对其病因、临床表现、影像学特点、诊断、治疗、预后及预防进行分析,其中13例患儿采用外科手术治疗,23例患儿采用内科药物治疗.结果 住院治疗期间有1例患儿死亡,其余35例存在不同程度的改善.出院后经过半个月～7年的随访,手术治疗的患儿中1例死亡,1例留有后遗症;保守治疗的息儿中1例死亡,4例留有后遗症.结论及时诊断、尽早积极采取综合治疗措施可提高此病的抢救成功率,降低病死率及致残率.进行大规模科普宣传,提高人们对此病的重视程度,加强各种预防措施,对降低该病的发病率十分重要.     

Bleeding and non-bleeding phenotypes in patients with GGCX gene mutations

Functional limitations for the vitamin K cycle, caused either by mutations in gamma-glutamyl carboxylase or vitamin K epoxide reductase genes, result in hereditary deficiency of vitamin K-dependent coagulation factors (VKCFD1 and VKCFD2, respectively). Patients suffering from VKCFD often share several other anatomical irregularities which are not related to haemostasis. Here we report on nine patients, eight of them previously unreported, who presented with VKCFD1. All were examined with special attention to vitamin K-dependent coagulation factors as well as to bone and heart development and to other anatomical signs of embryonal vitamin K deficiency. In total, we detected ten mutations in the gamma-glutamyl carboxylase gene of which seven have not been previously reported. Most interestingly, additional non-bleeding phenotypes were observed in all patients including midfacial hypoplasia, premature osteoporosis, cochlear hearing loss, heart valve defects, pulmonary stenosis, or pseudoxanthoma elasticum-like phenotype. Undercarboxylated matrix Gla protein, osteocalcin, and periostin appear to be responsible for these defects which are also observed in cases of fetal warfarin syndrome.     

Postoperative dementia: toxicity of nitrous oxide

INTRODUCTION: Post-operative neuropsychiatric manifestations represent a frequent situation and may be due to several aetiologies. The responsibility of vitamin B12 deficiency must be evoked, especially in case of anaesthesia with a currently used substance: nitrous oxide. CASE REPORT: A 65 year-old man with no medical history, presented problems walking and memory loss 16 days after surgery for femoral prosthesis. Neurological examination revealed paraplegia with syndrome of combined degeneration of the spinal cord. The exploration of cognitive functions showed disorientation in time with memory disorders and disturbance of executive functioning. There was no apraxia, aphasia or agnosia. There were neither psychotic symptoms nor mood changes. MMS was at 18/30. Red blood count revealed an anaemia with macrocytosis (MGV=120 3). Vitamin B12 rate was very low (less than 30 g/l). Folate blood level was normal. Brain MRI showed moderate cerebral atrophy. Other investigations led to the diagnosis of Biermer's disease (fundic atrophy at biopsy with presence in the serum of antibodies to intrinsic factor). The diagnosis of neurological attack related to a vitamin B12 deficiency secondary to Biermer's disease was established, but the appearance of disorders in the post-operative period suggested the existence of an added factor. The recovery of informations revealed that anaesthesia was maintained by nitrous oxide during two hours and the patient exhibited pre-operative anaemia with macrocytosis. The hypothesis of decompensation of latent vitamin B12 deficiency by nitrous oxide was evoked. Replacement therapy by vitamin B12 induced real improvement of the cognitive impairment. MMS increased to 25/30. DISCUSSION: Cognitive impairment due to vitamin B12 deficiency is rarely dominated by isolated memory disorders. An authentic dementia is exceptional. Our patient had a dementia diagnosed on the basis of DSM IV criteria including memory disorders, disturbance of executive functioning and significant impairment in social and occupational functioning, associated with a combined degeneration of the spinal cord, common in vitamin B12 deficiency. Furthermore, he had an unknown Biermer's disease responsible for pre-operative deficiency which was clinically latent (there was only macrocytosis anaemia). The appearance of problems in the post-operative period was due to an acute decompensation of the latent deficiency induced undoubtedly by nitrous oxide used in anaesthesia. According to Christensen, nitrous oxide causes irreversible oxidation of vitamin B12 cobalt's atom responsible for its inactivation and the appearance of clinical manifestations. Evolution under vitamin B12 replacement therapy depends on the rapidity of its founding. In our case, it led to an improvement, notably in cognitive functions. CONCLUSION: Through this observation, the authors underline the necessity to search for vitamin B12 deficiency in the case of cognitive features following general anaesthesia.     

Placental transfer of vitamin K1 and its implications in fetal hemostasis

Vitamin K status was evaluated using coagulation studies and/or vitamin K1 assays in a total of 53 normal fetuses and 47 neonates. Second trimester fetal blood samples were obtained for prenatal diagnosis under ultrasound guidance. Endogenous vitamin K1 concentrations (determined by high performance liquid chromatography) were substantially lower than maternal levels. The mean maternal-fetal gradient was 14-fold at mid trimester and 18-fold at birth. Despite low vitamin K levels, descarboxy prothrombin, detected by a staphylocoagulase assay, was elevated in only a single fetus and a single neonate. After maternal oral supplementation with vitamin K1, cord vitamin K1 levels were boosted 30-fold at mid trimester and 60-fold at term, demonstrating placental transfer. However, these levels were substantially lower than corresponding supplemented maternal levels. Despite elevated vitamin K1 concentrations, supplemented fetuses and neonates showed no increase in total or coagulant prothrombin activity. These results suggest that the low prothrombin levels found during intrauterine life are not due to vitamin K deficiency.     

Psychosis-induced vitamin D deficiency with secondary hyperparathyroidism and osteoporotic fractures

Vitamin D deficiency is common in patients with insufficient sunlight exposure and nutritional deficit in calcium and vitamin D. We present a patient with vitamin D deficiency, secondary hyperparathyroidism and resulting osteoporotic fractures caused or supported by psychosis-induced minimal sunlight exposure and nutritional deficits. To our knowledge, this is the first case where delusional ideas could have led to a vitamin D deficiency, secondary hyperparathyroidism and osteoporotic fractures. Similar clinical cases could be more often, but significantly underdiagnosed, among schizophrenia patients. An appropriate prevention by UV light exposure, food fortification and supplements is normally sufficient for patients at risk.