Casimir Funk: his discovery of the vitamins and their deficiency disorders.

The history of the discovery of vitamins is the history of their deficiency disorders. Their discoverer was Casimir Funk, who is considered the 'father of vitamin therapy'. In his experimental research, Funk studied the interrelationships in the human body of those elements that Eijkman had demonstrated in animals, particularly in birds.

The aristaless (Arx) gene: one gene for many "interneuronopathies".

The ARX (Aristaless-related (X-linked) homeobox) gene is not only present in arthropods and their ancestors, but also in vertebrates including humans (ARX orthologs). The gene is composed of 5 coding exons and it is expressed predominantly in foetal and adult brain and skeletal muscle. In this review we report on our experience and review the existing literature on the genotype and phenotype heterogeneity associated with ARX abnormalities in humans ranging from severe neuronal migration defects (e.

Pigmentary mosaicism, subcortical band heterotopia, and brain cystic lesions.

A 10-year-old boy presented with a severe and diffuse mosaic skin hypopigmentation running (in narrow bands) along the lines of Blaschko associated with mosaic areas of alopecia, facial dysmorphism with midface hypoplasia, bilateral punctate cataract, microretrognathia, short neck, pectus excavatum, joint hypermobility, mild muscular hypotonia, generalized seizures, and mild mental retardation. Cranial magnetic resonance imaging revealed hypoplastic corpus callosum (primarily posterior), subcortical band heterotopia, and diffuse subcortical, periventricular cystic-like lesions. Similar dysmorphic features were observed in the child's mother, but with no imaging abnormalities.

Prevalence of dementia in the rural island town of Ama-cho, Japan.

Background: With the striking increase in the number of elderly people in Japan, dementia has not only become a medical but also a social issue.

Methods: We studied the prevalence of dementing disorders in a rural island town of Japan (Ama-cho), using a door-to-door 2-phase design.

Results: Of the 120 persons screened as having cognitive impairment, 104 people were diagnosed as having dementia.

Neurofibromatosis type 1 and infantile spasms.

Background: There is no agreement on the prevalence, natural history and outcome of infantile spasms (IS) in neurofibromatosis type 1 (NF1). By contrast, its prevalence and outcome are well characterised in the setting of other neurocutaneous disorders (e.g.

Homocysteine is toxic for dopaminergic neurons in primary mesencephalic culture.

Hyperhomocysteinemia associated with L-3,4-dihydroxyphenylalanine (L-dopa) treatment has been observed in patients with Parkinson's disease. We investigated the toxicity of homocysteine (Hcy) on E14-rat-primary mesencephalic culture. Exposure to 0-5 mM Hcy decreased number of tyrosine hydroxylase (TH)-positive dopaminergic neurons and microtubule associated protein 2 (MAP2)-positive neurons in a dose-dependent manner.

Esophageal balloon dilation in children: prospective analysis of hemodynamic changes and complications during general anesthesia.

Study Objective: To investigate hemodynamic changes and complications in children during balloon dilation of esophageal strictures.

Design: Prospective, controlled study.

Setting: University teaching hospital.

Bilateral periventricular nodular heterotopia with amniotic band syndrome.

The amniotic (constriction) band syndrome is characterized by distal ring constrictions, intrauterine amputations, and acrosyndactyly. External constriction by amniotic bands is the generally accepted mechanism: early amniotic rupture leads to formation of mesodermal fibrous strands that constrict, entangle, and amputate distal portions of limbs. Etiology is heterogeneous.

Herpes zoster of the trigeminal nerve following microvascular decompression.

A patient developed herpes zoster of the maxillary division of the trigeminal nerve after microvascular decompression. Varicella zoster virus lies dormant in the Gasserian ganglion until reactivation and can cause herpes zoster ophthalmicus. This can result in serious ocular complications including blindness.

[Anti-Yo antibody associated paraneoplastic cerebellar degeneration with gastric adenocarcinoma in a male patient: a case report].

We report a 71-year-old man presenting with paraneoplastic cerebellar degeneration (PCD) associated anti-Yo antibody after surgery for gastric adenocarcinoma. Seven months after partial gastrectomy, he deviated to the right on walking. Furthermore, a feeling of dysarthria appeared and he was unable to sit after 2 months.

Genetic variation in the myeloperoxidase gene and cognitive impairment in multiple sclerosis.

There is evidence that multiple sclerosis (MS) may associated with cognitive impairment in 25 to 40% of cases. The gene encoding myeloperoxidase (MPO) is involved in molecular pathways leading to beta-amyloid deposition. We investigated a functional biallelic (G/A) polymorphism in the promoter region (-463) of the MPO gene in 465 patients affected by MS, divided into 204 cognitively normal and 261 impaired.

Electrocortical effects of MDMA are potentiated by acoustic stimulation in rats.

Background: 3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is known for its toxicological, psychopathological and abuse potential. Some environmental conditions, e.g.

Thiamine-responsive congenital lactic acidosis: clinical and biochemical studies.

We studied six infants with thiamine-responsive congenital lactic acidosis and normal pyruvate dehydrogenase complex activity in vitro, through clinical and biochemical analysis. In addition to elevated lactate and pyruvate levels, the data revealed increased urinary excretion of alpha-ketoglutarate, alpha-ketoadipate, and branched chain ketoacids, indicating functional impairment of thiamine-requiring enzymes, such as pyruvate dehydrogenase complex, alpha-ketoglutarate dehydrogenase complex, alpha-ketoadipate dehydrogenase, and branched chain amino acid dehydrogenase. The metabolism of thiamine has not been investigated in patients with thiamine-responsive congenital lactic acidosis.

Earliest clinical manifestations and natural history of neurofibromatosis type 2 (NF2) in childhood: a study of 24 patients.

Background: Neurofibromatosis type 2 (NF2) is an autosomal dominant disease characterised by the development of multiple nervous system tumours, ocular abnormalities, and skin tumours. Although classically considered a disease of adults, initial signs and/or symptoms may be evident in childhood and are often unrecognised.

Objectives: The aim of this study was to identify the earliest clinical presentations of NF2 and to characterise the clinical course and outcome in children with NF2.

Multiple sclerosis in children under 10 years of age.

Despite the consistent amount of information accumulated in recent years on multiple sclerosis (MS) in childhood, many clinicians still view this condition as an exclusively young adult-onset disease and do not consider that it may occur and manifest even during infancy and pre-school age, suggesting that the number of MS cases in the paediatric age group may have been underestimated. Thus, the need to have practical parameters for therapeutic, counselling and educational purposes in such settings as caring for patients whose onset of disease is at very early ages may increasingly arise for practising clinicians. In addition, the clinical and radiographic criteria for the diagnosis of MS have not been validated in a paediatric MS population; accordingly, inclusion age at onset (such as for research purposes) is generally over 10 years.

Ten years of experience with pediatric neuroendoscopic third ventriculostomy: features and perioperative complications of 210 cases.

Obstructive hydrocephalus remains a problem, and improvements in fiberoptic technology have promoted interest in neuroendoscopic ventriculostomy (NTV) as an alternative to standard cerebrospinal fluid shunts. The present study assessed 210 pediatric NTVs performed between 1994 and 2004 in patients aged 2 months to 10 years. Five children needed same-session ventriculoperitoneal shunting due to insufficient bypass of the obstruction.

Review of zonisamide development in Japan.

Zonisamide is a benzisoxazole-based compound first synthesized in the early 1970s by the research laboratories of Dainippon Pharmaceutical Company in Osaka, Japan. Identified as an anticonvulsant during exploratory research, zonisamide has since been characterized as having broad-spectrum antiepilepsy and neuroprotective effects. Early clinical studies in Japan demonstrated that zonisamide has a long elimination half-life and is well tolerated; Phase II and III clinical trials established the drug's efficacy and safety for the treatment of partial and generalized seizures.

Overview of Japanese experience-controlled and uncontrolled trials.

Zonisamide is a new type of benzisoxazole derivative, first marketed in Japan in 1989. This study analyzed: (1) the drug's efficacy by seizure and epilepsy type in a total of 1008 patients treated during the development of zonisamide in Japan; (2) the effectiveness of zonisamide for 726 newly-diagnosed patients treated with zonisamide postmarketing; and (3) 50 patients with generalized epilepsies and epileptic syndromes (idiopathic generalized epilepsies, symptomatic generalized epilepsies, Lennox-Gastaut syndrome, Doose syndrome, and West syndrome), and 19 patients with undetermined epilepsies and specific syndromes (refractory grand mal in childhood, severe myoclonic epilepsy in infancy, other undetermined epilepsy, familial essential myoclonic epilepsy, and mitochondrial encephalomyopathy with ragged-red fibers). Analysis of study results showed that among all patients treated, zonisamide was highly effective for the treatment of idiopathic generalized epilepsy, temporal lobe epilepsy, and other partial epilepsies.

Ophthalmological manifestations in segmental neurofibromatosis type 1.

Aims: To study the ophthalmological manifestations in individuals with the typical features of neurofibromatosis type 1 (NF1) circumscribed to one or more body segments, usually referred to as segmental NF1.

Methods: Visual acuity and colour tests, visual field examination, slit lamp biomicroscopy of the anterior segment, and a detailed examination of the retina by indirect ophthalmoscopy were performed at diagnosis and follow up in 72 consecutive subjects (29 males, 43 females; aged 1-64 years; mean age 14.6 years) seen at the university departments of paediatrics in Catania and Rome, Italy, during years 1990-2003, who had in restricted body areas: (1) typical pigmentary manifestations of NF1 (cafe au lait spots and freckling) only (n = 48); (2) NF1 pigmentary manifestations and neurofibromas alone (n = 2); (3) neurofibromas only (n = 15); and (4) plexiform neurofibromas only (n = 7).

Colour blindness in everyday life and car driving.

Purpose: The aim of the present work was to ascertain, through the administration of a psychosocial questionnaire, the difficulties that subjects with defective colour vision experience in carrying out everyday tasks and work, including driving a car with a driver's licence held for no more than 3 years.

Methods: Subjects with defective colour vision (n = 151) and subjects with normal vision (n = 302) completed a psychosocial questionnaire regarding the difficulties associated with congenital colour vision deficiency in daily life, work and driving a car. Subjects were diagnosed as colour-blind using the Ishihara test.

Delineation of a newly recognized neurocutaneous malformation syndrome with "cutis tricolor".

The term "cutis tricolor" describes the combination of congenital hyper- and hypo-pigmented lesions, in close proximity to each other with a background of normal skin. Cutis tricolor represents twin spotting and has been reported as an isolated skin disorder or as part of a neurocutaneous malformation syndrome. We report on an 11-year-old girl with diffuse pigmentary changes of the cutis tricolor type, facial anomalies, mental retardation, epileptic seizures, EEG anomalies, small skull, progressive double-curved thoracolumbar/lumbar scoliosis with vertebral scalloping and dysplastic vertebral pedicles and ribs, and tibial bowing.

Cardiac-restricted ankyrin-repeated protein is differentially induced in duchenne and congenital muscular dystrophy.

Cardiac ankyrin-repeated protein (CARP) has been shown to associate with a transcription factor, YB-1, that may activate expression of the ventricular myosin light chain-2 gene during cardiogenesis. CARP is induced in the adult hypertrophic heart subjected to pressure overload, suggesting that CARP may play important functional roles in both embryonic and adult hearts. Although CARP expression was initially believed to be restricted to the heart, we found recently that CARP is induced strongly in human fetal skeletal muscle and in experimentally denervated skeletal muscle, leading us to speculate that CARP may also play important roles in skeletal muscle.

Altered expression of cardiac ankyrin repeat protein and its homologue, ankyrin repeat protein with PEST and proline-rich region, in atrophic muscles in amyotrophic lateral sclerosis.

Objectives: Cardiac ankyrin repeat protein, CARP, is a protein that is restrictedly expressed in the heart but barely expressed in skeletal muscles. Since CARP is induced by pressure overload to the heart, it is proposed to be a genetic marker for cardiac hypertrophy. We recently identified a novel protein, ankyrin repeat protein with PEST and proline-rich region (ARPP), which is homologous to CARP and is preferentially expressed in type 1 skeletal muscle fibers (cf.