Acute Disseminated Encephalomyelitis (ADEM) Following Campylobacter jejuni Infection in a 12-Year-Old Girl

We reported a case of acute disseminated encephalomyelitis (ADEM) in a 12-year-old girl shortly after developing fever and vomiting, and ultimately found to have Campylobacter jejuni by antigen detection and conventional stool culture. Campylobacter jejuni has been associated with peripheral demyelinating diseases including Guillain–Barre's syndrome, but it has not been previously implicated in central demyelination in children. The clinical description and review of the literature are included here.

CENTRAL MYELIN AND DEMYELINATION

INTRODUCTION:CNS demyelinating disorders are common neurological illness that affects the brain. This causes signicant disability and mortality if not properly identied and treated. CNS demyelinating diseases includes multiple sclerosis, acute disseminated encephalomyelitis, NMO spectrum disorders and transverse myelits. Here we are reporting a case of central demyelination. CASE SUMMARY: 44yrs female admitted with subacute onset of weakness of all four limbs, more on left side and sensory disturbance in the form of numbness and tingling in all four limbs, more on left side, associated with urinary urgency and constipation. Patient had right optic neuritis 3 years back. General examination was normal. Vital signs were stable. On nervous system examination, patient had decresed visual acuity in right eye, with relative afferent pupillary defect and impaired red green colour vision, fundus was normal. Motor system examination, Patient had normal bulk, increased tone, brisk deep tendon reexes, power of 4 on right and 4- on left side with extensor planter on both sides. Patient had decresed sensation below C5 spinal cord level, predominantly joint position and vibration sense with positive lhermitte's sign. Other systems were normal. Routine lab investigation ,ECG,CXR were normal. CSF analysis revealed elevated protein of 72mg. MRI BRAIN WITH WHOLE SPINE SCREENING(contrast) revealed Multiple smallT2/FLAIR hyperintense lesion in bilateral juxta cortical, subcortical(involving the temporal lobes and callososeptal interface), subtle patchy enhancement in the left peritrigonal lesion and in body of corpus callosum. Mild atrophy of cervical cord from C3 to C5 with T2 hyperintense involving both hemicord from C2 to C5 level, focal Hyperintensity subtle contrast enhancement in Dorsal cord at the level of D11, Features suggestive of demyelination likely Multiple Sclerosis.

Clinical Features and Genetic Risk of Demyelination Following Anti-TNF Treatment

Background Anti-TNF exposure has been linked to demyelination events. We sought to describe the clinical features of demyelination events following anti-TNF treatment and to test whether affected patients were genetically predisposed to multiple sclerosis [MS]. Methods We conducted a case-control study to describe the clinical features of demyelination events following anti-TNF exposure. We compared genetic risk scores [GRS], calculated using carriage of 43 susceptibility loci for MS, in 48 cases with 1219 patients exposed to anti-TNF who did not develop demyelination. Results Overall, 39 [74%] cases were female. The median age [range] of patients at time of demyelination was 41.5 years [20.7–63.2]. The median duration of anti-TNF treatment was 21.3 months [0.5-99.4] and 19 [36%] patients were receiving concomitant immunomodulators. Most patients had central demyelination affecting the brain, spinal cord, or both. Complete recovery was reported in 12 [23%] patients after a median time of 6.8 months [0.1–28.7]. After 33.0 months of follow-up, partial recovery was observed in 29 [55%] patients, relapsing and remitting episodes in nine [17%], progressive symptoms in three [6%]: two [4%] patients were diagnosed with MS. There was no significant difference between MS GRS scores in cases (mean -3.5 × 10–4, standard deviation [SD] 0.0039) and controls [mean -1.1 × 10–3, SD 0.0042] [p = 0.23]. Conclusions Patients who experienced demyelination events following anti-TNF exposure were more likely female, less frequently treated with an immunomodulator, and had a similar genetic risk to anti-TNF exposed controls who did not experience demyelination events. Large prospective studies with pre-treatment neuroimaging are required to identify genetic susceptibility loci.

PATH-60. PRIMARY CNS LYMPHOMA PRECEDED BY ACUTE DEMYELINATION

Primary CNS lymphoma commonly presents with nonspecific encephalopathy or focal neurologic deficits. Magnetic resonance imaging typically shows a homogeneously enhancing mass with surrounding edema. The imaging differential diagnosis is broad, and includes high grade glioma and neuroinflammatory conditions. Definitive diagnosis therefore requires biopsy. Here we present a case of primary CNS lymphoma that was diagnosed as an acute demyelinating process on initial biopsy. A 68 year old female presented with gait instability and vertigo. MRI showed right cerebellar and right trigonal enhancing lesions. Biopsy revealed an acute demyelinating inflammatory process and she was diagnosed with acute disseminated encephalomyelitis. She was treated with intravenous methylprednisolone followed by oral prednisone with resulting clinical and radiographic improvement. She was re-admitted to hospital 4 months later with encephalopathy. Imaging showed a new enhancing mass in the pericallosal frontal lobes. Repeat brain biopsy showed diffuse large B-cell lymphoma. This case illustrates a highly unusual situation of biopsy-proven central demyelination preceding a primary CNS lymphoma diagnosis. It raises a number of etiopathological questions concerning the coexistence and potential causal relationships between demyelination and lymphoma. Additionally, it highlights the need for repeat biopsy if clinical and radiographic suspicion for lymphoma persists despite an alternative initial biopsy result.

118 Case series: subacute combined degeneration of the spinal cord in vitamin B12-replete recreational nitrous oxide abusers

IntroductionWithin a few years of its discovery in late 18th century, nitrous oxide was being used recreationally for its pleasurable effects. It remains in widespread use as an inhaled stimulant today, and can be legally acquired in bulk quantities with relative ease. In the body prolonged exposure to nitrous oxide leads to the oxidization of vitamin B12, rendering it unusable in key enzymatic reactions necessary for myelin synthesis. Over time this qualitative deficiency leads to a central demyelination syndrome that characteristically develops despite normal serum vitamin B12 levels and, with continued exposure to nitrous oxide, resists treatment with vitamin B12 supplementation.MethodNitrous oxide abusers presenting with a central demyelination syndrome were enrolled in this case series. Serum levels of vitamin B12, active B12, folate and homocysteine were measured. Nitrous oxide exposure was discontinued, and all patients were treated in accordance with evidence-based guidelines.ResultsEight patients presented with predominantly moderate-to-severe clinical deficits. The majority were vitamin B12 replete. In most cases individuals had actively engaged in prolonged vitamin B12 supplementation in an attempt to circumvent the harmful pathophysiology, of which they were loosely aware. Following treatment and rehabilitation several patients were discharged into full-time care, and most had significant residual disability at follow-up.ConclusionsThis case series not only illustrates the tragic consequences of abuse of this widely available and legally procured stimulant, but also highlights the futility of pursuing a nominally ‘protective’ strategy of vitamin B12 supplementation in the context of continued nitrous oxide exposure.

TrkB Agonist LM22A-4 Increases Oligodendroglial Populations During Myelin Repair in the Brain

The neurotrophin, brain-derived neurotrophic factor (BDNF) promotes central nervous system (CNS) myelination during development and after injury. This is achieved via activation of oligodendrocyte-expressed tropomyosin-related kinase (Trk) B receptors. However, while administration of BDNF has shown beneficial effects, BDNF itself has a poor pharmacokinetic profile. Here, we compare two TrkB-targeted BDNF-mimetics, the structural-mimetic, tricyclic dimeric peptide-6 (TDP6) and the non-peptide small molecule TrkB agonist LM22A-4 in the cuprizone model of central demyelination in female mice. Both mimetics promoted remyelination, increasing myelin sheath thickness and oligodendrocyte densities after one-week recovery. Importantly, LM22A-4 exerts these effects in an oligodendroglial TrkB-dependent manner. However, analysis of TrkB signaling by LM22A-4 suggests rather than direct activation of TrkB, LM22A-4 exerts its effects via indirect transactivation of Trk receptors. Overall, these studies support the therapeutic strategy to selectively targeting TrkB activation to promote remyelination in the brain.