Transient Clinical Improvement Research Articles

Brainstorm: A case of granulomatous encephalitis

Background: Free-living amoebas (FLAs) can cause severe and fatal central nervous system infections that are difficult to diagnose. Methods: We present the case of a 74-year-old immunocompetent woman admitted for focal neurological symptoms with enhancing lesions in the right cerebellar hemisphere. A first cerebral biopsy showed granulomatous inflammation, but no microorganisms were identified. After transient clinical improvement, she eventually deteriorated 4 months after initial presentation, with an MRI confirming multiple new masses affecting all cerebral lobes. Results: A second brain biopsy revealed granulomatous and acute inflammation with organisms containing a large central nucleus with prominent karyosome, consistent with FLAs. Immunohistochemical and polymerase chain reaction assays performed at CDC were positive for Acanthamoeba spp, confirming the diagnosis of granulomatous amoebic encephalitis (GAE) caused by Acanthamoeba spp. The patient was treated with combination therapy recommended by CDC, but died a few days later. Upon histopathological rereview, amoebic cysts and trophozoites were identified by histochemical and immunohistochemical methods in the first cerebral biopsy. Conclusion: FLA infections can be challenging to diagnose because of the low incidence, non-specific clinical and radiological presentation, lack of accessible diagnostic tools, and clinicians’ unfamiliarity. This case highlights the importance of recognizing FLA as a potential cause of granulomatous encephalitis, even in the absence of risk factors, as early treatment might be associated with favourable outcomes in case reports. When suspected, CDC laboratories offer tests to confirm the diagnosis promptly.

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) Initially Presenting as Septic Meningoencephalitis in a 16-Year-Old Male.

We describe a case of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) in a 16-year-old patient who initially presented with clinical features of septic meningoencephalitis. This case outlines the importance of considering a diagnosis of MOGAD in patients who fail to improve with appropriate antimicrobial therapy or show a positive clinical response to glucocorticoids (often used in treatment of meningococcal meningitis). We emphasise the importance of recognising that an infectious prodrome can precede MOGAD. A 16-year-old male was admitted with vomiting, fever, headache, photophobia and altered mental state. He was treated for meningoencephalitis with initial clinical improvement. Lumbar puncture findings were suggestive of viral meningoencephalitis. During admission the patient went through several periods of transient clinical and biochemical improvement, alternating with periods of symptomatic relapse. On day 17 of admission, he was transferred to a tertiary centre for suspected autoimmune disseminated meningoencephalitis (ADEM) and two days later, he suffered a catastrophic neurological decline with new dysarthria, dysphagia, aphasia, horizontal nystagmus and facial paralysis. He made a remarkable neurological recovery after commencing treatment with IV immunoglobulin, IV methylprednisolone and plasma exchange, with complete resolution of symptoms. MOGAD can run a variable course and present soon after a central nervous system infection, making the diagnosis more challenging. Nonetheless, patients can achieve a full neurological recovery with early recognition, diagnosis and treatment of this rare entity. Autoimmune encephalitis can be preceded by an infectious prodrome which makes the diagnosis more challenging.Autoimmune encephalitis can run a subacute and fluctuating course with transient periods of symptomatic improvement preceding a rapid neurological decline.Glucocorticoids often used in treatment of patients with meningococcal meningitis may lead to transient symptomatic improvement in patients with autoimmune encephalitis, masking the diagnosis.MRI findings of demyelination in autoimmune encephalitis may lag behind clinical symptoms by days to weeks.

Tazobactam/ceftolozane and tobramycin combination therapy in extensively drug-resistant Pseudomonas aeruginosa infections in severe burn injury: a case report

BackgroundCombination therapy with tazobactam/ceftolozane (TAZ/CTLZ) and high-dose aminoglycosides has been reported to be efficacious in extensively drug-resistant (XDR)-Pseudomonas aeruginosa infection. However, there are no reports of efficacy in XDR-P. aeruginosa infection for combination therapy with low-dose aminoglycosides and TAZ/CTLZ. Herein, we describe a rare case of severe burn injury patients with persistent bacteremia due to XDR-P. aeruginosa, which was successfully treated with TAZ/CTLZ and low-dose tobramycin (TOB).Case presentationA 31-year-old man was admitted to the intensive care unit with severe burn injury involving 52% of the total body surface area and a prognostic burn index of 79.5. The patient had recurrent bacterial infections since admission, and blood cultures collected on the 37th day of admission revealed the presence of P. aeruginosa strains that were resistant to all β-lactams and amikacin (AMK). The results of the antimicrobial synergistic study showed no synergistic effect of low-dose meropenem (MEPM) and AMK combination therapy. The patient had acute renal failure, and it was difficult to increase the dose of MEPM and AMK, respectively. Thus, we initiated TAZ/CTLZ 1.5 g/8 h instead of the AMK and MEPM combination therapy on the 43rd day of hospitalization. Low-dose TAZ/CTLZ was continued because of prolonged renal dysfunction and resulted in a transient clinical improvement. However, the dosage of TAZ/CTLZ could be increased as the renal function improved, but despite an increased TAZ/CTLZ dose, bacteremia persisted, and the blood cultures remained positive. Thus, TOB was added to TAZ/CTLZ at low doses for synergistic effect against Gram-negative bacteria. Blood cultures collected after initiation of combination therapy with TAZ/CTLZ and low-dose TOB were negative on two consecutive follow-up evaluations. Thereafter, although the patient had several episodes of fever and increased inflammatory response, blood cultures consistently tested negative, and all of the wounds healed. On the 93rd day, due to the good healing progress, the patient was transferred to another hospital.ConclusionsTAZ/CTLZ and low-dose TOB combination therapy showed the potential for synergistic effects. Our present report suggests a novel synergistic treatment strategy for rare cases that are refractory to the treatment of infections, such as XDR-P. aeruginosa infection.

USE OF INFLIXIMAB AS THERAPEUTIC OPTION FOR STEROID-RESISTANT PARADOXICAL REACTION IN TB

SESSION TITLE: TB and TB-Involved Case PostersSESSION TYPE: Case Report PostersPRESENTED ON: 10/17/2022 12:15 pm - 01:15 pmINTRODUCTION: Paradoxical reaction (PR) is an immune-mediated disease exacerbation precipitated by initiation of antitubercular therapy (ATT). Unlike IRIS (immune reconstitution inflammatory syndrome), a hyperinflammatory response to HIV/AIDS treatment, PR is independent of antiretroviral therapy (ART). Standard guideline therapy for PR is limited, with glucocorticoids as a standard of care. We describe a case of steroid-resistant tuberculin PR that improved with experimental Infliximab therapy.CASE PRESENTATION: 42-year-old HIV negative female with a history of rheumatoid arthritis on methotrexate and ovarian cancer on chemotherapy, presented with dyspnea and left-sided weakness. Chest imaging demonstrated a diffuse miliary pattern (image 1). QuantiFERON testing was positive. Cerebrospinal fluid studies, bronchoalveolar lavage and sputum cultures detected Mycobacterium tuberculosis (TB). Cultures demonstrated no antimicrobial resistance. Magnetic Resonance Imaging demonstrated lesions favoring CNS tuberculomas (image 2).There was transient clinical improvement with expanded ATT (Rifampin, Isoniazid, Pyrazinamide, Levofloxacin, Linezolid, Dexamethasone) but the disease continued to worsen despite increasing dosage of the glucocorticoid. Emergent salvage therapy with Infliximab significantly improved the intracranial and respiratory disease burden (image 3) with near resolution of clinical findings.DISCUSSION: An overexaggerated cell-mediated immune response against killed or damaged mycobacterium results in PR [1]. Moreover, granulomatous host response to TB may sequester the organism from administered antitubercular treatment [2]. Manipulation of immunomodulation by targeting tumor necrosis factor alpha (TNF alpha) is a proposed potential therapeutic option for PR [2] as it can decrease inflammation and disrupt granulomatous formations.CONCLUSIONS: There are only handful case reports exploring alternatives for steroid resistant PR. TNF-a inhibition is a potential valid treatment option in such cases [2].Reference #1: Blackmore, T. K., Manning, L., Taylor, W. J., & Wallis, R. S. (2008). Therapeutic Use of Infliximab in Tuberculosis to Control Severe Paradoxical Reaction of the Brain and Lymph Nodes. Clinical Infectious Diseases, 47(10), e83–e85. https://doi.org/10.1086/592695Reference #2: Briner, M., Oberholzer, M., Chan, A., & Wagner, F. (2021). Potential disease trigger as a therapeutic option: infliximab for paradoxical reaction in tuberculosis of the central nervous system. BMJ Case Reports, 14(8), e235511. https://doi.org/10.1136/bcr-2020-235511DISCLOSURES: No relevant relationships by Nicholas KlimbergNo relevant relationships by Pallabi ShresthaNo relevant relationships by Sarah UpsonNo relevant relationships by Kenji Yoshino SESSION TITLE: TB and TB-Involved Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Paradoxical reaction (PR) is an immune-mediated disease exacerbation precipitated by initiation of antitubercular therapy (ATT). Unlike IRIS (immune reconstitution inflammatory syndrome), a hyperinflammatory response to HIV/AIDS treatment, PR is independent of antiretroviral therapy (ART). Standard guideline therapy for PR is limited, with glucocorticoids as a standard of care. We describe a case of steroid-resistant tuberculin PR that improved with experimental Infliximab therapy. CASE PRESENTATION: 42-year-old HIV negative female with a history of rheumatoid arthritis on methotrexate and ovarian cancer on chemotherapy, presented with dyspnea and left-sided weakness. Chest imaging demonstrated a diffuse miliary pattern (image 1). QuantiFERON testing was positive. Cerebrospinal fluid studies, bronchoalveolar lavage and sputum cultures detected Mycobacterium tuberculosis (TB). Cultures demonstrated no antimicrobial resistance. Magnetic Resonance Imaging demonstrated lesions favoring CNS tuberculomas (image 2). There was transient clinical improvement with expanded ATT (Rifampin, Isoniazid, Pyrazinamide, Levofloxacin, Linezolid, Dexamethasone) but the disease continued to worsen despite increasing dosage of the glucocorticoid. Emergent salvage therapy with Infliximab significantly improved the intracranial and respiratory disease burden (image 3) with near resolution of clinical findings. DISCUSSION: An overexaggerated cell-mediated immune response against killed or damaged mycobacterium results in PR [1]. Moreover, granulomatous host response to TB may sequester the organism from administered antitubercular treatment [2]. Manipulation of immunomodulation by targeting tumor necrosis factor alpha (TNF alpha) is a proposed potential therapeutic option for PR [2] as it can decrease inflammation and disrupt granulomatous formations. CONCLUSIONS: There are only handful case reports exploring alternatives for steroid resistant PR. TNF-a inhibition is a potential valid treatment option in such cases [2]. Reference #1: Blackmore, T. K., Manning, L., Taylor, W. J., & Wallis, R. S. (2008). Therapeutic Use of Infliximab in Tuberculosis to Control Severe Paradoxical Reaction of the Brain and Lymph Nodes. Clinical Infectious Diseases, 47(10), e83–e85. https://doi.org/10.1086/592695 Reference #2: Briner, M., Oberholzer, M., Chan, A., & Wagner, F. (2021). Potential disease trigger as a therapeutic option: infliximab for paradoxical reaction in tuberculosis of the central nervous system. BMJ Case Reports, 14(8), e235511. https://doi.org/10.1136/bcr-2020-235511 DISCLOSURES: No relevant relationships by Nicholas Klimberg No relevant relationships by Pallabi Shrestha No relevant relationships by Sarah Upson No relevant relationships by Kenji Yoshino

Pseudotumoral pulmonary tuberculosis secondary to a paradoxical reaction in an immunocompetent patient from Benin: A case report

Paradoxical reactions (PR) during tuberculosis treatment are rare in HIV negative subjects and result in polymorphic clinical presentations which could sometimes lead to confusion. We report the case of a postpartum mother, HIV negative who was placed on treatment for pulmonary tuberculosis. She experienced transient clinical improvement and developed PR which mimicked lung malignancy. This is a rare phenomenon and may result in diagnostic and therapeutic dilemma in resource poor settings.

MM-218: Renal Failure Reversal in Bi-Clonal Multiple Myeloma Treated with Daratumumab, Cyclophosphamide, and Dexamethasone as a Second-Line Treatment

Renal failure (RF) is known to be reversal reversible in multiple myeloma (MM) and is associated with improved survival. We hereby present a case of a 52-year-old female who was diagnosed in February 2020 with bi-clonal multiple myeloma, where the immunofixation showed 2 pics, IgGκ and free light chain kappa, associated with acute renal failure. Lab tests showed creatinine of 7 mg/dl and Hb of 7 g/dL. The bone marrow biopsy was consistent with MM and showed 18% aberrant plasma cells (PCs). The immunohistochemistry study showed CD38+ and kappa+. Induction chemotherapy with VRD, bortezomib 1.3 mg/m2, revlimid 25 mg, and steroid dexamethasone 40 mg was initiated for 2 cycles, with hemodialysis. After 2 cycles of VRD, a transient clinical improvement was noted but without enhanced renal function amelioration. The serum protein electrophoresis (SPEP) for IgGκ was repeated and found to be decreased, from 42 g/l to 1.9 g/l, with major increases in the free light chain kappa from 42 to 995 mg/dl and B2-microglobulin from 24 to 47 mcg/l. Second-line treatment was initiated with daratumumab 16 mg/kg, cyclophosphamide 600 mg/m2, and dexamethasone 40 mg, taking into consideration that the patient was resistant to proteasome inhibitor and immunomodulatory drugs (IMiDs). After 2 months of treatment, there was an amelioration of kidney function, with normalization of creatinine to 3.2 mg/dl. The patient stopped her hemodialysis, and the free light chain kappa decreased to 53 mg/dl. The patient is proposed to have ASCT after finishing her second-line treatment and reevaluation.

Osteomyelitis caused by Aggregatibacter aphrophilus – a case report

Osteomyelitis in children is often secondary to haematogenous dissemination of bacteria into long bone metaphyses. Organisms causing osteomyelitis vary with age, and the virulence of different pathogens influences clinical presentation.1 Aetiological diagnosis is important in determining appropriate antibiotic therapy. This case involves an 11-year-old girl with 4 months worsening left knee pain and difficulty weight bearing. She had no fever, preceding trauma or recent dental procedures. Inflammatory markers were unremarkable, with radiological evidence of a Brodie’s abscess. She was trialled on oral cephalexin; despite transient clinical improvement, she re-presented with worsening symptoms. She was afebrile, with distal femoral point tenderness, no evidence of knee joint involvement and 1/6 mid-systolic murmur at the pulmonic area. Intravenous flucloxacillin was commenced, with debridement and washout of the distal femoral lesion. Surgical specimens grew Aggregetibacter aphrophilus sensitive to ampicillin, with negative blood cultures. Transthoracic echocardiography showed no valvular abnormalities. Her mobility improved, and she was transitioned to amoxicillin, with planned duration of 3 months. Aggregetibacter aphrophilus is a low virulence HACEK group bacterial pathogen with potential to cause osteomyelitis.2 This case of an uncommon, low-virulence pathogen causing osteomyelitis shows the importance of aetiological diagnosis to guide appropriate management, especially in cases with indolent presentations. 1.Arnold JC, Bradley JS. Osteoarticular infections in children. Infect Dis Clin North Am 2015; 29: 557–74.2.Norskov-Lauritsen N, Kilian M. Reclassification of Actinobacillus actinomycetemcomitans, Haemophilus aphrophilus, Haemophilus paraphrophilus and Haemophilus segnis as Aggregatibacter actinomycetemcomitans gen. nov., comb. nov., Aggregatibacter aphrophilus comb. nov. and Aggregatibacter segnis comb. nov., and emended description of Aggregatibacter aphrophilus to include V factor-dependent and V factor-independent isolates. Int J Syst Evolutionary Microbiol 2006; 56: 2135–46.

MON-250 Late Diagnosis of ACTH-secreting Pulmonary Neuroendocrine Tumor by Repeated 68Ga Dotatate Pet/ct: Influence of Tumor Size in Abnormal Uptake?

Background: 68Ga DOTATATE PET/CT (68Ga-PET) has been proposed as a superior method in identifying ectopic ACTH syndrome (EAS). However, recent systematic review suggests its sensitivity is not as high as believed (1). We report a challenging case of EAS whose source was uncovered only after repeated 68Ga-PET. Clinical Case: A 15‐year-old male presented with rapid onset of typical features of Cushing’s syndrome (CS) and metabolic impairment. Hormone evaluation confirmed severe ACTH-dependent CS. Pituitary transsphenoidal surgery was performed due to positive responses in desmopressin stimulation and high dose dexamethasone suppression test, in addition to a 4 mm nodule in pituitary MRI. No tumor was found in surgical specimen and no hormonal improvement was observed after surgery. Inferior petrosal sinus sampling demonstrated no central to peripheral ACTH gradient. Neck US, thorax/abdomen/pelvis CT were negative and PET-CT/FDG was inconclusive. OctreoScan® identified anomalous uptake on left mediastinum and led the patient to a thoracic surgery (TS) with nodule resection at left hilum. Pathology confirmed ACTH positive 10 mm neuroendocrine tumor (NET) infiltrating a lymph node. The patient had transient clinical and hormonal improvement, with recurrence 7 months later. Thoracic CT (T-CT) showed a 7 mm nodule on inferior segment of superior left lobe, PET-CT/FDG and OctreoScan® were negative but abnormal uptake was verified by 68Ga-PET in subcarinal area. A sub centimetric lymph node was resected and pathology confirmed ACTH positive NET, although the patient did not achieve remission. Octreotide LAR, cabergoline and ketoconazole did not control hypercortisolism and bilateral adrenalectomy was performed. Then, T-CT showed stable lung nodule and 2nd 68Ga-PET was negative. One year later, T-CT evidenced growth of lung nodule to 15 mm and 3rd 68Ga-PET demonstrated for the first time, abnormal uptake in this area. The patient underwent resection of left superior lung lobe along with ipsilateral hilar lymph nodes, and histopathology study revealed an ACTH-secreting atypical pulmonary carcinoid tumor with Ki67 of 10% and 5 out of 11 lymph nodes affected. ACTH fell from 288 to 64 pg/mL after surgery. Conclusion: Despite the high sensitivity attributed to 68Ga-PET, false negatives have been reported. In the present case, primary tumor was evidenced by 68Ga-PET seven years after the first resection of a metastatic lymph node, in the 3rd 68Ga-PET assessment and after tumor growth. This adds to the evidence that further studies are needed to better assess the accuracy of 68Ga-PET for EAS. Reference: [1] Varlamov et al. Diagnostic utility of Gallium‐68‐somatostatin receptor PET/CT in ectopic ACTH‐secreting tumors: a systematic literature review and single‐center clinical experience. Pituitary 2019; 22:445–455

Delta-24-RGD combined with radiotherapy exerts a potent antitumor effect in diffuse intrinsic pontine glioma and pediatric high grade glioma models

Pediatric high grade gliomas (pHGG), including diffuse intrinsic pontine gliomas (DIPGs), are aggressive tumors with a dismal outcome. Radiotherapy (RT) is part of the standard of care of these tumors; however, radiotherapy only leads to a transient clinical improvement. Delta-24-RGD is a genetically engineered tumor-selective adenovirus that has shown safety and clinical efficacy in adults with recurrent gliomas. In this work, we evaluated the feasibility, safety and therapeutic efficacy of Delta-24-RGD in combination with radiotherapy in pHGGs and DIPGs models. Our results showed that the combination of Delta-24-RGD with radiotherapy was feasible and resulted in a synergistic anti-glioma effect in vitro and in vivo in pHGG and DIPG models. Interestingly, Delta-24-RGD treatment led to the downregulation of relevant DNA damage repair proteins, further sensitizing tumors cells to the effect of radiotherapy. Additionally, Delta-24-RGD/radiotherapy treatment significantly increased the trafficking of immune cells (CD3, CD4+ and CD8+) to the tumor niche compared with single treatments.In summary, administration of the Delta-24-RGD/radiotherapy combination to pHGG and DIPG models is safe and significantly increases the overall survival of mice bearing these tumors. Our data offer a rationale for the combination Delta-24-RGD/radiotherapy as a therapeutic option for children with these tumors.SignificanceDelta-24-RGD/radiotherapy administration is safe and significantly increases the survival of treated mice. These positive data underscore the urge to translate this approach to the clinical treatment of children with pHGG and DIPGs.

Spontaneous non-traumatic tension pneumocephalus in a dog with a nasal meningoencephalocele

A 1.5-year-old neutered male Border collie was presented with acute onset left forebrain signs and unilateral nasal discharge 14 months after MRI diagnosis of nasal meningoencephalocele. Subsequent MRI revealed intraventricular...

A lifelong study of a pack Rhodesian ridgeback dogs reveals subclinical and clinical tick-borne Anaplasma phagocytophilum infections with possible reinfection or persistence

BackgroundVarious tick-borne infections often occur without specific clinical signs and are therefore notoriously hard to diagnose separately in veterinary practice. Longitudinal studies over multiple tick seasons performing clinical, serological and molecular investigations in parallel, may elucidate the relationship between infection and disease. In this regard, six related Rhodesian Ridgeback dogs living as a pack became subject of lifetime studies due to ongoing tick infestations and recurring clinical problems. Blood samples for diagnostic tests were obtained throughout the years 2000 to 2009.MethodsData collected from clinical observations, hemograms, serology and detection of Anaplasma phagocytophilum, either by microscopy or by DNA amplification and typing, were placed in a time line. This dataset essentially presents as a prospective study enabling the association of the Anaplasma infections with occurring disease.ResultsAll six dogs were infected, and two of them developed particular clinical symptoms that could be associated with Anaplasma infections over time. More specifically, episodes of general malaise with fever and purpura with thrombocytopenia and bacterial inclusions in granulocytes, were found concurrently with Anaplasma DNA and specific antibodies in peripheral blood samples. DNA from A. phagocytophilum variant 4 (of 16S rRNA) was found in multiple and sequential samples. DNA-sequences from variant 1 and the human granulocytic ehrlichiosis (HGE) agent were also detected.ConclusionsIn this study two lifelong cases of canine anaplasmosis (CGA) are presented. The data show that dogs can be naturally infected concurrently with A. phagocytophilum variant 1, variant 4 and the HGE agent. The ongoing presence of specific antibodies and Anaplasma DNA in one dog indicates one year of persisting infection. Treatment with doxycycline during recurring clinical episodes in the other dog resulted in transient clinical improvement and subsequent disappearance of specific antibodies and DNA suggesting that re-infection occurred.

192 Multi-Watt Near Infrared Phototherapy is an Effective Treatment for Depression

AbstractBackgroundDepression treatment is hampered by low efficacy of antidepressant medications and concerns about alternative modalities. Animal studies of treatment with low-level (0.5 Watt or less) near infrared (NIR) light from diodes has shown some benefit in models of traumatic brain injury (TBI) with evidence of reduced lesion size, increased neurotrophin production, synaptogenesis, fewer apoptotic cells, and improved neurological function. Two small case series have demonstrated transient clinical improvement with low-level NIR treatment given on a daily basis over several weeks. We have previously shown marked and persistent clinical improvement in a case series of patients with chronic mild-to-moderate (m-MTBI) after treatmentwith NIR at a power of 9 Watts or greater. We also have published a review of the potential for application of NIR for the treatment of depression. The current study explores NIR efficacy in a proof-of-concept study as a treatment for depression.MethodsThirty-nine sequential patients treated for TBI between March 2013 and May 2017 provided depression self-assessment data and/or were administered the Hamilton Depression Rating Scale. Each completed the Quick Inventory of Depression Symptomatology-Self Reports (QIDS) before and after treatment. Patients received transcranial multi-Watt near-infrared light treatment (NILT) using near-infrared lasers (810/980 nm at 8-15 Watts) applied to forehead and temporal regions bilaterally for 9-12 minutes to each area.ResultsFor 36 of the 39 patients, after 16.82 + 6.26 treatments, QIDS scores indicated a robust response (decrease of QIDS total score by > 50%). For 32 of 39 patients post-treatment QIDS scores indicated a remission from depression (decrease of QIDS total score < 5). Overall, the QIDS score fell from 14.10 + 3.39 to 3.44 + 3.39 SD (p=6.29 X 10-19). With 12 or fewer treatments, QIDS score dropped from 14.83 + 2.55 to 4.17 + 3.93. Patients receiving 13 or more treatments showed a change in QIDS score from 13.67 + 3.64 to 3.11 + 3.14. Those (N=15) who received the entire treatment course within 8 weeks or less (5.33 + 1.72 weeks) showed a change in QIDS score from 13.86 + 3.14 to 4.5 + 3.94. Suicidal ideation resolved in all, but two patients. The non-responsive patients are described in detail. Patients remained in remission for up to 55 months after a single course of treatment.ConclusionThis is the first report of high-powered NILT showing efficacy for depression. Patients saw benefit often within 4 treatments and some had resolution of depressive symptoms in as little as 4 weeks. These data raise an intriguing possibility – that NILT may be a safe, effective, and rapid treatment for depression. A double-blind, placebo controlled trial is warranted to verify these proof-of-concept data.Funding AcknowledgementsNeuro-Laser Foundation

Augmented cartilage regeneration by implantation of cellular versus acellular implants after bone marrow stimulation: a systematic review and meta-analysis of animal studies.

Bone marrow stimulation may be applied to regenerate focal cartilage defects, but generally results in transient clinical improvement and formation of fibrocartilage rather than hyaline cartilage. Tissue engineering and regenerative medicine strive to develop new solutions to regenerate hyaline cartilage tissue. This systematic review and meta-analysis provides a comprehensive overview of current literature and assesses the efficacy of articular cartilage regeneration by implantation of cell-laden versus cell-free biomaterials in the knee and ankle joint in animals after bone marrow stimulation. PubMed and EMBASE (via OvidSP) were systematically searched using tissue engineering, cartilage and animals search strategies. Included were primary studies in which cellular and acellular biomaterials were implanted after applying bone marrow stimulation in the knee or ankle joint in healthy animals. Study characteristics were tabulated and outcome data were collected for meta-analysis for studies applying semi-quantitative histology as outcome measure (117 studies). Cartilage regeneration was expressed on an absolute 0–100% scale and random effects meta-analyses were performed. Implantation of cellular biomaterials significantly improved cartilage regeneration by 18.6% compared to acellular biomaterials. No significant differences were found between biomaterials loaded with stem cells and those loaded with somatic cells. Culture conditions of cells did not affect cartilage regeneration. Cartilage formation was reduced with adipose-derived stem cells compared to other cell types, but still improved compared to acellular scaffolds. Assessment of the risk of bias was impaired due to incomplete reporting for most studies. Implantation of cellular biomaterials improves cartilage regeneration compared to acellular biomaterials.

A rare case of multiple pituitary adenomas in an adolescent Cushing disease presenting as a vertebral compression fracture.

Cushing disease in children and adolescents, especially with multiple pituitary adenomas (MPAs), is very rare. We report 17-year-old boy with MPAs. He presented with a vertebral compression fracture, weight gain, short stature, headache, and hypertension. On magnetic resonance imaging (MRI), only a left pituitary microadenoma was found. After surgery, transient clinical improvement was observed but headache and hypertension were observed again after 3 months later. Follow-up MRI showed a newly developed right pituitary microadenoma 6 months after the surgery. The need for careful clinical and radiographic follow-up should be emphasized in the search for potential MPAs in patients with persistent Cushing disease.

Myoclonus epilepsy and ataxia due to KCNC1 mutation: Analysis of 20 cases and K+ channel properties.

To comprehensively describe the new syndrome of myoclonus epilepsy and ataxia due to potassium channel mutation (MEAK), including cellular electrophysiological characterization of observed clinical improvement with fever. We analyzed clinical, electroclinical, and neuroimaging data for 20 patients with MEAK due to recurrent KCNC1 p.R320H mutation. In vitro electrophysiological studies were conducted using whole cell patch-clamp to explore biophysical properties of wild-type and mutant KV 3.1 channels. Symptoms began at between 3 and 15 years of age (median = 9.5), with progressively severe myoclonus and rare tonic-clonic seizures. Ataxia was present early, but quickly became overshadowed by myoclonus; 10 patients were wheelchair-bound by their late teenage years. Mild cognitive decline occurred in half. Early death was not observed. Electroencephalogram (EEG) showed generalized spike and polyspike wave discharges, with documented photosensitivity in most. Polygraphic EEG-electromyographic studies demonstrated a cortical origin for myoclonus and striking coactivation of agonist and antagonist muscles. Magnetic resonance imaging revealed symmetrical cerebellar atrophy, which appeared progressive, and a prominent corpus callosum. Unexpectedly, transient clinical improvement with fever was noted in 6 patients. To explore this, we performed high-temperature in vitro recordings. At elevated temperatures, there was a robust leftward shift in activation of wild-type KV 3.1, increasing channel availability. MEAK has a relatively homogeneous presentation, resembling Unverricht-Lundborg disease, despite the genetic and biological basis being quite different. A remarkable improvement with fever may be explained by the temperature-dependent leftward shift in activation of wild-type KV 3.1 subunit-containing channels, which would counter the loss of function observed for mutant channels, highlighting KCNC1 as a potential target for precision therapeutics. Ann Neurol 2017;81:677-689.

Fecal Microbial Transplantation in Early‐Onset Colitis

Fecal Microbial Transplantation in Early‐Onset Colitis

P26 – 2615: Landau Kleffner syndrome following a minor head trauma – Case report

Background Landau Kleffner syndrome (LKS) is well defined epileptic encephalopathy best described by the synonym – acquired epileptic aphasia. Etiopathogenesis remains unknown. Structural lesions are rare. A few published cases postulated triggering role of head trauma in functional disconnection of cortical speech areas. Objective To evaluate the clinical presentation and management of a boy with LKS following a minor head trauma. Case report and results A ten years old boy of far consanguineous parents, at his age of six developed a generalized tonic clonic seizure following a head trauma two weeks before upon fall. The immediate period was uneventful, the child had only nose bleeding, brain CT was normal. However, consequent EEG showed ESES and he was started on valproates. Noncompliance led to another seizure six months later. Over that period, gradual regression in the ability to use or comprehend spoken language was noted. EEG showed more or less pronounced bilateral ESES affecting predominantly left temporo-parietal regions. Perinatal period and developmental before the onset of the illness were normal. Family history was unremarkable. Metabolic work up was normal. MRI brain done twice was unremarkable. Neurological status, apart from aphasia, was normal. Parents reported impulsivity and cognitive decline. He had one episode of focal seizure two years since the onset, but further has remained controlled. He went through several antiepileptic drugs combinations including valproates, clobazam, levetiracetam, clonazepam and lamotrigine. Ethosuximide was stopped due to intolerance. Two trials with oral prednisolone: the first lasting four months, complicated by hypertension, the second, of one month prednisolone with evening diazepam, resulted in transient clinical and EEG moderate improvement. Ketogenic diet was recommended. Conclusion Aphasia, inspite of various therapeutical attempts and favorable seizure control, remained the main concern. Corticosteoids transiently and partially improved the condition. Possible role of head trauma in LKS etiopatogenesis needs further consideration.

Sweet Syndrome and Pulmonary Tuberculosis in a CrohnÂ’s Disease Patient Treated with Anti-TNFα

A 36-year-old man with Crohn’s Disease (CD), under infliximab therapy, was admitted with fever and skin lesions on the face, trunk and upper limbs. Skin biopsy was consistent with Sweet Syndrome (SS). He was treated with corticosteroids, with transient clinical improvement, but without healing of skin lesions. After 2 weeks, the fever relapsed and the patient complained of night sweats. Chest X-ray and CT-scan revealed pulmonary diffuse micronodular pattern with a condensation suggestive of pulmonary tuberculosis. Tuberculin test and IGRA were positive. Bronchoalveolar lavage culture was positive for M. tuberculosis. The patient started anti-tuberculosis standard regimen and discontinued anti-TNFα therapy. During treatment, there was clinical and radiological worsening and development of CD flare. We admitted an immune reconstitution inflammatory syndrome and anti- TNFα was reintroduced after 2 months, with improvement in CD symptoms, complete healing of skin lesions and resolution of TB. To our knowledge, this is the first case reported in the literature that presents the association between SS and pulmonary tuberculosis in a patient on anti-TNFα treatment for CD, complicated with IRIS. Early recognition of this association is essential for a effective treatment. Diagnosis and therapy of SS and pulmonary tuberculosis in a patient with CD are herein discussed.

Numb chin syndrome secondary to leptomeningeal carcinomatosis from gastric adenocarcinoma.

Numb chin syndrome (NCS) can be a sign of malignancy. Its association with gastric adenocarcinoma is rare. We report a case of a 27-year-old Hispanic female that presented with complaint of left sided headache associated with numbness of the left side of chin and lower gingiva. Initial brain MRI, whole body gallium scan, high resolution CT of chest and elevated protein in the CSF were suggestive of sarcoidosis. She was treated with IV steroids with transient clinical improvement. Two weeks later, her symptoms worsened and further evaluation revealed the diagnosis of a poorly differentiated metastatic gastric adenocarcinoma with leptomeningeal involvement. This case report aims to emphasize the importance of identifying NCS as a possible indication of an underlying malignant condition. Reported cases of NCS associated with metastatic gastric adenocarcinoma are very rare.

PReS-FINAL-2086: In vitro investigation of the sustained therapeutic effect of etanercept loaded microspheres on human rheumatoid arthritis fibroblast-like synoviocytes

Anti-TNFα treatment has become an important part of our systemic treatment in chronic inflammatory arthritis. Local application to the joint produces transient clinical improvement since the drug quickly leaves the joint.