Spinal cord MRI in clinically isolated optic neuritis

BACKGROUND/METHODS: One hundred and fifteen patients with clinically isolated optic neuritis underwent magnetic resonance imaging (MRI) of the brain and spinal cord within 3 months of the onset of symptoms. RESULTS: Eighty one (70%) patients had brain lesions and 31 (27%) had cord lesions. Cord lesions were seen in 12% with a normal brain MRI, 21% with between one and eight brain lesions, and 45% with nine or more brain lesions. When the new diagnostic criteria for MS were applied, MRI cord imaging used for evidence of dissemination in time and space allowed a diagnosis of MS in only one additional asymptomatic patient at 1 year, two additional asymptomatic patients at 3 years. CONCLUSIONS: Using existing criteria, spinal cord imaging rarely contributes to the diagnosis in patients with clinically isolated optic neuritis.     

Contacting the host: insights and implications of pathogenic Neisseria cell interactions

Neisseria is a highly adapted human specific pathogen that initiates infection at the mucosal epithelia by using multiple adhesins to interact with host cell receptors. Colonization begins at the apical cell surface with a multi-step adhesion cascade, followed by invasion and persistence within the cell and finally transcytosis at the basolateral surface. The type IV pill are implicated in mediating the initial attachment of both meningococci and gonococci, and this association has been shown to involve contact with the cellular receptor CD46. In this review we describe the initial events in the adhesion, invasion and signaling of pathogenic Neisseria focusing on the initial attachment and signaling induced by the interaction of the type IV pili with CD46.     

Does a kidney-sharing alliance have to sacrifice cold ischemic time for better HLA matching?

BACKGROUND: The Scotland-Northern Ireland Kidney Allocation Alliance was created in August 1998. The purpose was to optimize the transplant service through increased regional exchange, higher quality matched kidneys, and better organ distribution. METHODS: An analysis was performed on prospectively collected data regarding retrieval and transplant activity. The degree of HLA matching, the cold ischemic time (CIT), the balance of exchange, and graft survival were analyzed for a 2-year period after the introduction of the new alliance and compared with the last year before alliance. RESULTS: There was a 17.7% increase in the number of transplants performed. In the 2-year period, 78% of kidneys were exported from the retrieving center compared with 55% in the prealliance year, (P<0.05, chi2). The proportion of 000 mismatched transplants and other favorable matches increased from 9.5 to 21% and from 52.5 to 61%, respectively. There was no significant difference between the CIT for the three study periods, nor between the CIT for locally used kidneys versus those exchanged within the Alliance (P>0.05, Student's t test). The largest center was a net importer of kidneys, whereas small and medium-sized centers balanced their exchange within the 2-year period. The 1-year transplant survival rate improved from 81.5% in the prealliance year to 88.4% at the end of the second year. CONCLUSIONS: The introduction of a regional kidney allocation alliance has improved the degree of HLA matching and increased the exchange of organs, without a significant increase in the CIT and any detrimental effect on graft survival.     

Presenilin-1 mutations alter K+ currents in the human neuroblastoma cell line,SH-SY5Y

Mutations in presenilin 1 (PS1) are the major cause of autosomal dominant Alzheimer's disease. We have measured the voltage-gated K+ current in the human neuroblastoma cell line SH-SY5Y using whole-cell patch-clamp. When cells were stably transfected to over-express PS1, no change in K+ current was observed. However, over-expression of a deletion mutation (deltaE9) in PS1 led to a decreased K+ current. These changes were channel specific since no change in the Na+ current could be observed in the same cells. Confocal microscopy revealed that the K(V)3.1 K+ channel subunit had a diminished plasma membrane distribution when the deltaE9 over-expressing cells were compared to control cells. Intracellular retention of Kv3.1 is consistent with the notion that PS1 can modulate the activity and trafficking of ion channels in central neurones and implicates a compromise in electrical signalling as an underlying factor in the pathogenesis of familial Alzheimer's disease.     

B Cell lymphoma of the brain stem masquerading as myasthenia

A 54 year old man is described with signs compatible with ocular myasthenia gravis and an apparent excellent response to pyridostigmine. Subsequent clinical progression and further investigation suggested the presence of an inflammatory brain stem lesion, which responded to corticosteroid therapy. Clinical relapse, including the development of central neurogenic hyperventilation, led to a brain stem biopsy, confirming a diagnosis of B cell lymphoma. This case illustrates the propensity of primary CNS lymphoma (PCNSL) to mimic other conditions. Brain MRI is mandatory in presumed "test negative" ocular myasthenia with atypical clinical findings. Spontaneous regression of PCNSL or response to corticosteroids is common and should not mitigate against the diagnosis. Histopathological confirmation should ideally be made before starting therapy, as this may obscure or delay the correct diagnosis. Although PCNSL is rare, it must be considered in all patients with brain stem syndromes, and in all patients 50 years or older with contrast enhancing focal lesions.     

Comment on ‘Predicting recurrence in axillary node negative breast cancer patients’, by Rosner and Lane

on behalf of the Nottingham Breast Unit     

Neural and musculoskeletal contributions to the development of stance balance control in typical children and in children with cerebral palsy

Studies on the development of automatic postural responses in both typically developing children and children with cerebral palsy were performed. With the appearance of "pull-to-stand" behavior, typically developing children first began to show muscle responses to platform movements in mainly the ankle muscles. With increased development, additional agonist muscles were added to the response pattern and a consistent distal to proximal sequence began to emerge. Well-organized responses were seen with the onset of independent stance and walking, along with the reduction of antagonist muscle co-activation. The older children with cerebral palsy who were pre-walkers had immature muscle activation patterns like those seen in the typically developing children at the pull-to- stand stage of development. These included disorganized muscle responses and increased frequency of coactivation of both proximal–distal and agonist–antagonist muscles. In order to determine if musculoskeletal constraints contributed to these response patterns, normal children were asked to stand in a crouched posture similar to that of children with CP. This caused postural muscle response patterns to more closely approximate those of children with spastic diplegia.