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IntroductionImmune-mediated encephalitis can occur in the absence of measurable pathogenic antibodies in CSF or serum.Methods and resultsWe present the case of a 29-year-old Sudanese woman presented with four days history of meningism. She is three months post-partum with her fifth child and does not have significant past medical history. She is a current smoker with history of methamphetamine and heroin use until 5 years ago. There were no focal neurological deficits on examination. CT brain was normal and her CSF had 420×106/L leucocytes (Polymorphs 18, Mononuclears 402). Three days later, she deteriorated clinically with GCS 11 and developed left sided hemiplegia requiring intubation and ventilation in intensive care.The CSF culture along with autoimmune encephalitis panel, anti-neuronal antibodies, HSV, VZV, Enterovirus, cryptococcal antigen, TB quantiferon, HIV, Malaria were negative. Her immunology tests were unremarkable including rheumatoid factor, complements, anti-nuclear antibodies, dsDNA, PR3, MPO, RNP, Smith, Ro, La, Scleroderma 70 and Jo-1 antibodies. The MRI Brain showed persistent changes in right hemispheric cortical and subcortical gyriform FLAIR hyperintensities which were also present in DWI images. The EEG showed right temporo-occipital region 7–8 Hz rhythmic discharges with generalised diffuse slowing. She had right parietal lobe brain biopsy which shows perivascular and intramural inflammation by mononuclear cells almost comprised of CD3 T-cells consistent with encephalitis associated with secondary lymphocytic vasculitis. She was treated with intravenous pulsed methylprednisolone and IVIg followed by plasma exchange. Then given high dose oral corticosteroids with slow tapering and intravenous Cyclophosphamide four weekly. Significant neurological improvement noted over next 8 weeks with patient being alert and participating in ongoing multidisciplinary rehabilitation for hemiplegia.ConclusionA case of cerebral biopsy confirmed, CSF and serum antibody-negative encephalitis is presented.

Carbamazepine (CBZ) is the gold standard antiepileptic drug (AED) for focal onset seizures. Despite CBZ being the benchmark AED, with readily available therapeutic drug monitoring, patients presenting with recurrent secondarily generalized tonic-clonic (or cluster) seizures or generalized tonic-clonic status epilepticus (SE) are primarily treated with other long-acting agents. The aim of the study was to examine the potential use of rectal (PR) CBZ as alternative long-acting treatment to parenteral AEDs following the termination of cluster seizures or SE with acute intravenous therapies. Oral CBZ syrup was given PR using 400-mg equivalent aliquots. Serum CBZ levels were requested after administration to confirm achievement of minimum therapeutic levels (total CBZ>20μmol·L(-1)). Where levels were subtherapeutic, the procedure was repeated using 400-mg CBZ bolus aliquots until therapeutic levels were achieved. Seven patients received PR CBZ to manage cluster seizures or SE following the initial termination of acute seizures with IV therapies including benzodiazepines. Six patients had no prior history of seizures, and 1 patient with a prior history was not taking AED therapy at the time of presentation. All patients subsequently remained seizure-free, and therapeutic CBZ levels were achieved in 6 of the 7 subjects within 5-10h of initial CBZ dosing. In conclusion, the present study reports 7 patients who were safely and effectively treated with PR CBZ, which proved to be a viable and safe alternative to parenteral AEDs for maintenance of seizure freedom.

We report a 37-year-old woman with a 2 month history of proximal muscle weakness and extremely high creatine kinase (21,808 U/L) due to necrotizing auto-immune myositis (NAM) in association with anti-synthetase syndrome. Myositis-specific auto-immune antibody panel was positive for anti-Signal recognition particle and anti-PL-12. CT scan of the chest confirmed interstitial lung disease. Prednisolone, intravenous immunoglobulin and cyclophosphamide therapy was given with gradual improvement. This patient is notable for the unusual combination of NAM and anti-synthetase syndrome with the rare finding of two myositis-specific autoantibodies, which directed testing for associated extramuscular features and management with more aggressive immunotherapy.

The anti-synthetase syndrome is a rare, autoimmune multi-system disorder of unclear etiology characterized by a variable combination of inflammatory myositis, interstitial lung disease, Raynaud’s phenomenon and arthritis. Serum autoantibodies to aminoacyl-tRNA synthetase (Anti-PL-12) are often present. The prognosis of the disease is largely determined by the pulmonary involvement. Prednisone with or without azathioprine and methotrexate have been used for myositis, while cyclophosphamide should be considered for severe pulmonary involvement. Anti SRP associated necrotizing autoimmune myositis is part of the spectrum of autoimmune inflammatory myopathies. It is characterized by the presence of signal recognizing particle antibodies which may occur in isolation or in some cases, in conjunction with other serum auto-antibodies. We describe a rare and interesting case of a 37 year old female who presented with a progressive proximal muscle weakness involving the upper and lower limbs in association with lethargy. She also displayed Raynaud’s phenomenon and complained of exertional shortness of breath. She had extremely high creatine kinase levels (22,000) U/L and electrophysiological confirmation of an active myositis. She had positive anti SRP antibodies and muscle biopsy findings of a necrotizing autoimmune myositis. In addition, she had anti-PL-12 antibodies and evidence of interstitial lung disease on pulmonary function tests and CT lung imaging. Her constellation of symptoms, signs and investigative findings were consistent with an anti-synthetase syndrome. She was treated initially with methylprednisone, azathioprine and IVIG without significant improvement. Her myositis and ILD partially responded to IV cyclophosphamide therapy. This case demonstrates a unique patient with anti-synthetase syndrome in association with anti-SRP and anti-PL-12 myositis specific antibodies. It highlights the use of myositis-specific antibody testing in assisting the diagnosis and choice of therapy. Further studies are required to determine the occurrence of multiple myositis specific antibodies in necrotizing myopathies and if their presence correlates with prognosis and treatment response.