Timothy J. Counihan

T-cells expressing natural killer (NK) receptors are altered in multiple sclerosis and responses to α-galactosylceramide are impaired

Multiple sclerosis (MS) is an autoimmune disorder characterised by clinical relapse and remission and pathological demyelination with varying inflammation. Because it is suggested that T-cells expressing natural killer cell receptors (NKR) play important roles in regulating human autoimmune diseases, we have quantified populations of T-cells expressing the NKR CD56, CD161 and CD94 in the peripheral blood of MS patients, in healthy control subjects (HS) and in patients with other neurological diseases (OND). CD161(+) T-cells and CD94(+) T-cells were significantly decreased in MS patients with primary progressive disease and secondary progressive disease respectively whereas CD56(+) T-cell numbers were unchanged. In contrast NKT-cells that express the invariant Valpha24-Jalpha18(+) T-cell receptor identified here by specific receptor antibody and CD1d-tetrameric PBS57-loaded complexes, were increased in MS patients compared with HS. Reductions in CD161(+) T-cells and CD94(+) T-cells relative to HS were also observed in the OND group and this was particularly prominent in Parkinsonian patients. A striking functional finding was that while NKT-cells in unfractionated peripheral blood from healthy subjects expanded in number and produced IFN-gamma upon stimulation with alpha-galactosylceramide, NKT-cells from MS patients did not. Thus we have identified alterations in a number of potentially important lymphocyte sub-populations warranting further investigation in the immune response in MS.

Maternal brain death: medical, ethical and legal issues

Case presentationWe present the case of a pregnant woman who experienced a cerebral venous sinus thrombosis resulting in brain death at 13xa0weeks gestation. We discuss the management of the mother and foetus following this tragic event. We also discuss the complex medical, legal and ethical issues that arose following maternal brain death. The central question is whether continuing maternal organ supportive measures in an attempt to prolong gestation to attain foetal viability is appropriate, or whether it constitutes futile care.DiscussionSuccessful maintenance of maternal brain somatic function to facilitate foetal maturation in utero has been reported. While the gestational age of the foetus is central to resolving this issue, there is no clear upper physiological limit to the prolongation of somatic function following brain death. Furthermore, medical experience regarding prolonged somatic support is limited. Finally, the legal rights conferred on the foetus may vary significantly depending on the jurisdiction in which the maternal brain death occurs and may have important implications.ConclusionsA consensus building approach, involving the family, is essential to resolving these potentially conflicting issues.

Perineuritis in acute lyme neuroborreliosis

Perineuritis is an unusual cause of direct peripheral nerve injury. We describe the clinicopathologic features of a 56‐year‐old man with mononeuritis multiplex due to Lyme disease; sural nerve biopsy demonstrated florid perineuritis. Treatment with intravenous ceftriaxone resulted in marked neurologic improvement. This study supports the notion that perineuritis forms part of the pathogenesis in acute Lyme neuroborreliosis. Muscle Nerve, 2009

Invariant Natural Killer T-cell anergy to endogenous myelin acetyl-glycolipids in multiple sclerosis

To extend our studies on glycolipid-reactive invariant Natural Killer T-cell (iNKT-cell) function in multiple sclerosis (MS), we investigated the stimulatory activities of two myelin-derived glycolipids that are poly-acetylated derivatives of β-galactosylceramide designated as fast-migrating cerebrosides (FMC) by thin-layer chromatography. In healthy subjects, FMC stimulation of peripheral blood cells significantly expanded iNKT-cells similar to α-GalCer and induced significant increases in Th1, Th2 and Th17 cytokines. In marked contrast, MS patients failed to respond to FMCs or to α-GalCer stimulation indicating an anergic response. We propose that myelin-derived FMC glycolipids stimulate iNKT-cell responses in vivo and this is blocked in MS.

Acute aseptic meningitis and diffuse myelitis as the presenting features of neurological Behcet disease

We report an explosive presentation of neurological Behcet disease, in an Irish male patient. We present the clinical and radiological findings in our patient and discuss a novel and effective therapeutic approach. We review other treatment modalities of patients with neurological involvement.

Facial diplegia and deafness following a fall

A 45-year-old man presented to the emergency department (ED) after falling down two flights of stairs. He had bilateral raccoon eyes, subconjunctival haemorrhages and CSF otorrhoea suggestive of skull base fracture (SBF). Although he had difficulty speaking and responded inappropriately, giving the impression of mixed dysphasia, written communication was normal, and he complained of deafness and dizziness. n nFacial motion was barely perceptible and complete eye closure was not possible, consistent with grade 5 facial palsies on the House-Brackmann facial nerve grading system. Bell’s phenomena (Fig.xa01) and dysarthrophonia secondary to facial weakness were marked. He was also mildly ataxic. Computed tomography (CT) imaging confirmed extensive SBF and audiometric testing confirmed bilateral deafness. High-resolution axial petrous temporal bone CT (Fig.xa02) demonstrated fractures involving the facial canals. The right-sided fracture traversed the fundus of the internal auditory canal, likely transecting the cochlear nerve, and the left-sided fracture involved the otic capsule, likely disrupting auditory and vestibular function. n n n nFig.xa01 n na A 45-year-old man with facial diplegia. b Patient attempting to close both eyes producing bilateral Bell’s phenomenon. c Magnification of b demonstrating marked bilateral Bell’s phenomenon (more pronounced on the right side) n n n n n nFig.xa02 n nRight and left axial petrous temporal bone CT. Right axial CT shows a medial subtype of horizontal temporal bone fracture. There is a fracture of the posterior petrous surface (white arrow) extending anteriorly through the fundus of the internal auditory ... n n n nPost-traumatic facial nerve palsy complicates 1.5% of SBFs involving the temporal bones [1]. Petrous temporal bone fractures may disrupt the facial nerve, membranous labyrinth and inner ear. While cranial nerves seven and eight may be injured by petrous temporal bone fractures, concomitant bilateral facial weakness and deafness in this setting is extremely rare [2]. Most post-traumatic facial nerve injuries recover with conservative management and time [3, 4]. n nThis case illustrates how bilateral facial weakness and deafness may be mistaken for mixed dysphasia and highlights the need to consider it in patients with apparent speech disturbances in the ED.