Case report: Use of granulocyte-colony stimulating factor as an immunomodulatory therapy in a patient with neuromyelitis optica spectrum disorder and comorbid immunodeficiency

BackgroundAutoimmune diseases can coexist with immunodeficiency. We describe a treatment approach in which granulocyte-colony stimulating factor (G-CSF) is used to restore immune competence without worsening autoimmunity. G-CSF is a polyfunctional cytokine that influences survival, proliferation, and differentiation of hematopoietic stem cells, and has immunomodulatory effects on the innate and adaptive immune systems.ObjectiveTo report a case of neuromyelitis optica spectrum disorder (NMOSD) with comorbid immunodeficiency and frequent infections.MethodsCase report and review of literature.ResultsA 23 years-old man presented with a focal onset seizure with impaired awareness at age 12. At age 18, he developed headaches, recurrent multifocal seizures, and non-convulsive status epilepticus. Brain magnetic resonance imaging (MRI) showed extensive T2 hyperintense and gadolinium-enhancing periventricular and corpus callosum lesions. Serum aquaporin 4 antibody was positive 1:10,000 (normal value <1.5 titer), hence he was diagnosed with NMOSD. As a complication, patient developed mucormycotic pneumonia with cavitation, requiring thoracotomy precluding use of immunosuppressants. Gene testing demonstrated a mutation in MT-ND4 gene encoding for NADH dehydrogenase 4 in mitochondrial complex 1. Eventually, he began a treatment with filgrastim, a G-CSF analog, in addition to intravenous immunoglobulins and prednisone. Patient’s NMOSD has been in remission without relapses, or coexistent infections ever since.ConclusionG-CSF is a polyfunctional cytokine with important immunomodulatory effects, which makes it an interesting therapeutic option when autoimmunity coexists with immunodeficiency and was used successfully in this case

International consensus recommendations for management of new onset refractory status epilepticus including febrile infection-related epilepsy syndrome: Statements and supporting evidence

Objective: This study was undertaken to develop consensus-based recommendations for the management of adult and pediatric patients with new onset refractory status epilepticus (NORSE)/febrile infection-related epilepsy syndrome (FIRES) based on best evidence and experience. Methods: The Delphi methodology was followed. A facilitator group of nine experts was established, who defined the scope, users, and suggestions for recommendations. Following a review of the current literature, recommendation statements concerning diagnosis, treatment, and research directions were generated, which were then rated on a scale of 1 (strongly disagree) to 9 (strongly agree) by a panel of 48 experts in the field. Consensus that a statement was appropriate was reached if the median score was ≥7 and inappropriate if the median score was ≤3. The analysis of evidence was mapped to the results of each statement included in the Delphi survey. Results: Overall, 85 recommendation statements achieved consensus. The recommendations are divided into five sections: (1) disease characteristics; (2) diagnostic testing and sampling; (3) acute treatment; (4) treatment in the postacute phase; and (5) research, registries, and future directions in NORSE/FIRES. The detailed results and discussion of all 85 statements are outlined herein. A corresponding summary of findings and practical flowsheets are presented in a companion article. Significance: This detailed analysis offers insight into the supporting evidence and the current gaps in the literature that are associated with expert consensus statements related to NORSE/FIRES. The recommendations generated by this consensus can be used as a guide for the diagnosis, evaluation, and management of patients with NORSE/FIRES, and for planning of future research

Selective and coherent activity increases due to stimulation indicate functional distinctions between episodic memory networks

Posterior-medial and anterior-temporal cortical networks interact with the hippocampus and are thought to distinctly support episodic memory. We causally tested this putative distinction by determining whether targeted noninvasive stimulation could selectively affect neural signals of memory formation within the posterior-medial network. Stimulation enhanced the posterior-medial network's evoked response to stimuli during memory formation, and this activity increase was coherent throughout the network. In contrast, there was no increase in anterior temporal network activity due to stimulation. In addition, control stimulation of an out-of-network prefrontal cortex location in a separate group of subjects did not influence memory-related activity in either network. The posterior-medial network is therefore a functional unit for memory processing that is distinct from the anterior temporal network. These findings suggest that targeted stimulation can lead to network-specific increases in excitability during memory formation and hold promise for efforts to fine-tune network involvement in episodic memory via brain stimulation © 2018 The Authors, some rights reserved

Data_Sheet_1_Case report: Use of granulocyte-colony stimulating factor as an immunomodulatory therapy in a patient with neuromyelitis optica spectrum disorder and comorbid immunodeficiency.PDF

BackgroundAutoimmune diseases can coexist with immunodeficiency. We describe a treatment approach in which granulocyte-colony stimulating factor (G-CSF) is used to restore immune competence without worsening autoimmunity. G-CSF is a polyfunctional cytokine that influences survival, proliferation, and differentiation of hematopoietic stem cells, and has immunomodulatory effects on the innate and adaptive immune systems.ObjectiveTo report a case of neuromyelitis optica spectrum disorder (NMOSD) with comorbid immunodeficiency and frequent infections.MethodsCase report and review of literature.ResultsA 23 years-old man presented with a focal onset seizure with impaired awareness at age 12. At age 18, he developed headaches, recurrent multifocal seizures, and non-convulsive status epilepticus. Brain magnetic resonance imaging (MRI) showed extensive T2 hyperintense and gadolinium-enhancing periventricular and corpus callosum lesions. Serum aquaporin 4 antibody was positive 1:10,000 (normal value ConclusionG-CSF is a polyfunctional cytokine with important immunomodulatory effects, which makes it an interesting therapeutic option when autoimmunity coexists with immunodeficiency and was used successfully in this case.</p

Supplementary Materials

Supplementary Material

Data from: Network-targeted stimulation engages neurobehavioral hallmarks of age-related memory decline

Objective: To test whether targeting hippocampal-cortical brain networks with high-frequency transcranial magnetic stimulation (TMS) in older adults influences behavioral and neural measures characteristic of age-related memory impairment. Methods: Fifteen adults aged 64 – 80 years (mean = 72 years) completed a single-blind, sham-controlled experiment. Stimulation targets in parietal cortex were determined based on functional magnetic resonance imaging (fMRI) connectivity with the hippocampus. Recollection and recognition memory were assessed after five consecutive daily sessions of full-intensity stimulation versus low-intensity sham stimulation using a within-subjects crossover design. Neural correlates of recollection and recognition memory formation were obtained via fMRI, measured within the targeted hippocampal-cortical network versus a control frontal-parietal network. These outcomes were measured ~24 hours after the final stimulation session. Results: Recollection was specifically impaired in older adults compared to a young-adult control sample at baseline. Relative to sham, stimulation improved recollection to a greater extent than recognition. Stimulation increased recollection fMRI signals throughout the hippocampal-cortical network, including at the targeted location of the hippocampus. Effects of stimulation on fMRI recollection signals were greater than those for recognition and were greater in the targeted network compared to the control network. Conclusions: Age-related recollection impairments were causally related to hippocampal-cortical network function in older adults. Stimulation selectively modified neural and behavioral hallmarks of age-related memory impairment, indicating effective engagement of memory intervention targets in older adults

International consensus recommendations for management of new onset refractory status epilepticus (NORSE) including febrile infection-related epilepsy syndrome (FIRES): Summary and clinical tools

Objective: To develop consensus-based recommendations for the management of adult and pediatric patients with new-onset refractory status epilepticus (NORSE)/febrile infection-related epilepsy syndrome (FIRES) based on best available evidence and expert opinion. Methods: The Delphi methodology was followed. A facilitator group of nine experts was established who defined the scope, users, and suggestions for recommendations. Following a review of the current literature, recommendation statements concerning diagnosis, treatment, and research directions were generated that were then voted on using a scale of 1 (strongly disagree) to 9 (strongly agree) by a panel of 48 experts in the field. Consensus that a statement was appropriate was reached if the median score was greater than or equal to 7, and inappropriate if the median score was less than or equal to 3. Results: Overall, 85 recommendation statements achieved consensus. The recommendations are divided into five sections: (1) disease characteristics; (2) diagnostic testing and sampling; (3) acute treatment; (4) treatment in the post-acute phase; and (5) research, registries, and future directions in NORSE/FIRES. These are summarized in this article along with two practical clinical flowsheets: one for diagnosis and evaluation and one for acute treatment. A corresponding evidence-based analysis of all 85 recommendations alongside responses by the Delphi panel is presented in a companion article. Significance: The recommendations generated by this consensus can be used as a guide for the diagnosis; evaluation; and management of patients with NORSE/FIRES; and for planning of future research