Increased longevity and refractoriness to Ca(2+)-dependent neurodegeneration in Surf1 knockout mice.

Leigh syndrome associated with cytochrome c oxidase (COX) deficiency is a mitochondrial disorder usually caused by mutations of SURF1, a gene encoding a putative COX assembly factor. We present here a Surf1-/- recombinant mouse obtained by inserting a loxP sequence in the open reading frame of the gene. The frequency of -/-, +/+ and +/- genotypes in newborn mice followed a mendelian distribution, indicating that the ablation of Surf1 is compatible with postnatal survival.

Upper eyelid gold weight implants in patients with facial nerve palsy. Surgical technique.

Facial nerve injuries produce lagophthalmos and consequent ocular disease caused by corneal exposure. The management of the affected eye in patients with facial palsy has been improved. Previously ointment, eye drops, taping, partial or complete tarsorrhaphy was the primary treatment of the inability to close the eyelid.

Pravastatin in vivo reduces mononuclear cell migration through endothelial monolayers.

The objective was to evaluate pravastatin modulation on peripheral blood mononuclear cell (PBMC) migration across endothelial monolayers. Eleven hypercholesterolaemic patients were treated with pravastatin 20 mg/day. At baseline (T0), after 40 days (T40) and after 6 months (T 6 months) of treatment total serum cholesterol, low-density lipoprotein (LDL), high-density lipoprotein, triglycerides, C-reactive protein, as well as tumour necrosis factor-alpha (TNF-alpha) and metalloproteinases-9 plasma levels were evaluated.

Architectural (Type IA) focal cortical dysplasia and parvalbumin immunostaining in temporal lobe epilepsy.

Purpose: We analyzed 26 surgically treated patients operated on for intractable epilepsy associated with type IA (architectural) cortical dysplasia, to investigate neuropathologic and immunocytochemical features, particularly of the gamma-aminobutyric acid (GABA)ergic system, and to compare the findings with those observed in normal cortex.

Methods: Routinely stained slides and serial sections immunostained for neurofilaments (SMI 311), microtubule-associated protein-2 (MAP-2), neuron-specific nuclear protein (NeuN), glial fibrillary acidic protein (GFAP), parvalbumin (PV), calbindin (CB), and calretinin (CR) were processed. Some sections were processed by using single-immunoperoxidase procedures; others were processed for double immunofluorescence labelling and observed by confocal microscopy.

GJA12 mutations in children with recessive hypomyelinating leukoencephalopathy.

Background: Pelizaeus-Merzbacher-like disease (PMLD) is an inherited hypomyelinating leukoencephalopathy with onset in early infancy. Like Pelizaeus-Merzbacher disease (PMD), PMLD is characterized clinically by nystagmus, cerebellar ataxia, and spasticity, due to a permanent lack of myelin deposition in the brain. Mutations in the GJA12 gene, encoding connexin 47 (Cx47), were recently reported in five children with autosomal recessive PMLD.

MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion.

The mitochondrial (mt) DNA depletion syndromes (MDDS) are genetic disorders characterized by a severe, tissue-specific decrease of mtDNA copy number, leading to organ failure. There are two main clinical presentations: myopathic (OMIM 609560) and hepatocerebral (OMIM 251880). Known mutant genes, including TK2, SUCLA2, DGUOK and POLG, account for only a fraction of MDDS cases.

Childhood-onset multifocal motor neuropathy with conduction blocks.

Multifocal motor neuropathy (MMN) is an acquired disorder with onset in adulthood. The authors describe a patient with a slowly progressing distal upper limb motor neuropathy since age 6 years, in whom definite conduction blocks in upper limbs, outside common entrapment sites, and no sensory involvement were consistent with MMN. IV immunoglobulin treatment produced marked muscle strength improvement and conduction block disappearance.

Atypical transverse myelitis due to cytomegalovirus in an immunocompetent patient.

Cytomegalovirus (CMV)-associated transverse myelitis is rare in immunocompetent patients. We report a 73-year-old man with no evidence of immune compromise, who developed acute transverse myelitis. Cerebrospinal fluid pleocytosis indicated central nervous system inflammation, and spinal MRI showed weak signal hypointensity in T1, hyperintensity in T2 and DP between C7 and T2, but no contrast enhancement.

A post-marketing study on immunomodulating treatments for relapsing-remitting multiple sclerosis in Lombardia: preliminary results.

The preliminary results of a post-marketing study on relapsing-remitting multiple sclerosis patients treated with immunomodulating agents attending the Lombardia Region's Multiple Sclerosis Centers are presented. A total of 294 patients treated with Betaferon (67), Avonex (115), Rebif 22 (45), Rebif 44 (18) and Copaxone (49) were included. Relapse frequency consistently decreases at 1 year and continues to decrease after 5 years of treatment, without differences between therapeutic groups.

A key regulatory role for histamine in experimental autoimmune encephalomyelitis: disease exacerbation in histidine decarboxylase-deficient mice.

Histamine can modulate the cytokine network and influence Th1 and Th2 balance and Ab-isotype switching. Thus, pharmacological blockade or genetic deletion of specific histamine receptors has been shown to reduce the severity of experimental autoimmune encephalomyelitis (EAE), a prototypic Th1-mediated disease with similarities to human multiple sclerosis. To study the comprehensive contribution of endogenous histamine to the expression of EAE, we attempted to induce EAE in histidine decarboxylase-deficient mice, which are genetically unable to make histamine.

Production and post-surgical modification of VEGF, tPA and PAI-1 in patients with glioma.

Malignant gliomas are associated with risk of thromboembolism, but the molecular link between tumor and peripheral pro-coagulant status has not been elucidated. Vascular Endothelial Growth Factor (VEGF), tissue-type Plasminogen Activator (tPA), Plasminogen Activator Inhibitor-1 (PAI-1) and lipoprotein (lp) (a) influence the pro-coagulant status. To assess whether the presence of the tumor influenced the peripheral levels of VEGF, tPA, PAI-1 and lp(a), we studied the expression and secretion of VEGF, tPA, PAI-1 and lp(a) in glioma specimens, in peripheral blood and in primary glioma-derived cultures.

ETHE1 mutations are specific to ethylmalonic encephalopathy.

Mutations in ETHE1, a gene located at chromosome 19q13, have recently been identified in patients affected by ethylmalonic encephalopathy (EE). EE is a devastating infantile metabolic disorder, characterised by widespread lesions in the brain, hyperlactic acidaemia, petechiae, orthostatic acrocyanosis, and high levels of ethylmalonic acid in body fluids. To investigate to what extent ETHE1 is responsible for EE, we analysed this gene in 29 patients with typical EE and in 11 patients presenting with early onset progressive encephalopathy with ethylmalonic aciduria (non-EE EMA).

Mitochondrial disorders.

Although mitochondrial disorders have been known for more than thirty years, a major breakthrough in their understanding came much later with the discovery of an impressive number of mutations in mitochondrial DNA (mtDNA). Partial deletions, duplications, or maternally inherited point mutations of mtDNA have been associated with well-defined clinical syndromes. Given the complexity of mitochondrial genetics and biochemistry, the clinical manifestations of mitochondrial disorders are extremely heterogeneous.

Disability pattern in chronic migraine with medication overuse: a comparison with migraine without aura.

Objectives: To assess headache-related disability in chronic migraine with medication overuse (CMO), as defined by Silberstein and Lipton (1996, 2001) in comparison to that caused by migraine without aura, investigating similarities and differences in disability patterns in these two conditions.

Background: It is well known that migraine has a marked impact on daily activities. Less information is available on the functional consequences of chronic migraine.

Persistent fixed torticollis due to Atlanto-axial rotatory fixation: report of 4 pediatric cases.

Atlanto-axial rotatory fixation (AARF) is a rare cause of childhood torticollis that may occur spontaneously or in association with trauma and upper respiratory infections. We describe the clinical findings, as well as the effectiveness of imaging in the diagnosis and the treatment of 4 children with AARF, in whom acute fixed non-dystonic torticollis was the presenting symptom. Onset of torticollis was spontaneous in Case 1, after general anesthesia for cholesteatoma surgery in Case 2, after a trauma in Case 3, and during hypersomnia in Case 4.

Magnesium as a treatment for paediatric tension-type headache: a clinical replication series.

The objective was to determine the initial utility of magnesium salt as a treatment for paediatric episodic and chronic tension-type headache (TTH). The study took the form of a clinical replication series in the Outpatient Headache Center at the National Neurological Institute "C. Besta", Milan, Italy.

In vitro effects of topotecan and ionizing radiation on TRAIL/Apo2L-mediated apoptosis in malignant glioma.

The survival of patients with malignant gliomas is still unsatisfactory despite multimodality treatment, therefore new therapeutic strategies are required. Tumor necrosis factor apoptosis related ligand (TRAIL/Apo2L), a member of the tumor necrosis factor superfamily, may induce apoptotic cell death in several tumors, but not in normal cells, upon binding with specific receptors. In the present study, the expression and function of TRAIL receptors (TRAIL-R1/DR4 and TRAIL-R2/DR5) has been investigated in five human glioma cell lines (U87, U138, U373, A172, SW1783) in ex vivo tumors and in primary cultures obtained from the tumors.

Sensorimotor cortex excitability in Unverricht-Lundborg disease and Lafora body disease.

Objective: To investigate whether Unverricht-Lundborg disease (ULD) and Lafora body disease (LBD) can be differentiated on the basis of their neurophysiologic profiles.

Methods: Somatosensory evoked potentials (SSEPs), long-loop reflexes (LLRs), and the influence of conditioning nerve stimulation on the motor potentials evoked by transcranial stimulation in 8 patients with LBD and 10 patients with ULD were investigated.

Results: Both groups showed sensorimotor cortex hyperexcitability, but their electrophysiologic profiles were different.

The multiple sclerosis functional composite: different practice effects in the three test components.

Background: The multiple sclerosis functional composite (MSFC) is a multidimensional, MS-specific outcome measure for use in clinical trials, comprising three tests: timed 25-foot walk (T25FW), paced auditory serial addition (PASAT), and 9-hole peg (9HP).

Objective: To assess interrater and intrarater reliability and practice/fatigue effects in the MSFC.

Methods: The MSFC was administered by two neurologists after a formal training session to 32 MS outpatients.

Mitochondrial myopathy and ophthalmoplegia in a sporadic patient with the 5698G-->A mitochondrial DNA mutation.

We describe a second patient carrying the 5698G-->A transition in the mitochondrial DNA gene encoding tRNA(Asn), who has an apparently isolated mitochondrial myopathy with chronic progressive external ophthalmoplegia. A muscle biopsy showed the presence of ragged-red and COX-negative fibres. Analysis of the mutation load on single muscle fibres showed significant segregation of the 5698G-->A with COX-depleted fibres.

Trigeminal autonomic cephalalgias: from pathophysiology to clinical aspects.

The strictly unilateral headaches, more commonly known as trigeminal autonomic cephalalgias (TACs), are characterised by severe, strictly unilateral pain in the territory of the distribution of the trigeminal nerve, associated with autonomic manifestations. The recent International Headache Society classification lists the strictly unilateral headaches as cluster headache (CH), episodic and chronic paroxysmal hemicrania, and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing. CH is the most common and best-defined of the TACs, whose pathophysiologies have not been adequately defined.

Chronic migraine with medication overuse: treatment outcome and disability at 3 years follow-up.

Patients with chronic migraine and medication overuse are particularly difficult to treat. No clear consensus exists about treatment strategies to be used and little data exists about the functional impact of headache in these patients. The purpose of the study was to determine (1) the clinical course of a sample of chronic migraine patients with medication overuse 36 months following treatment intervention and (2) whether functional impairment, assessed by the Migraine Disability Assessment (MIDAS) questionnaire, improved upon treatment.