The biological logic behind the connection between a foodborne diarrhoeal pathogen and a paralysing neurological disease is molecular mimicry. Certain C. jejuni strains express sialylated lipooligosaccharide (LOS) structures on their outer membrane that structurally resemble human peripheral nerve gangliosides such as GM1, GD1a, and GT1a. IgG autoantibodies raised against these bacterial LOS molecules cross-react with gangliosides on human nerve cells, damaging them and triggering the syndrome. The fine specificity of this mimicry is determined in part by a single amino acid polymorphism at position 51 of the sialyltransferase Cst-II: an asparagine residue (Asn51) renders the enzyme bifunctional, producing disialylated GT1a and GD3 mimics associated with Miller Fisher syndrome, whereas a threonine residue (Thr51) yields a monofunctional enzyme that generates GM1 and GD1a mimics linked to the acute motor axonal neuropathy variant of Guillain-Barré syndrome.

The second major surface antigen of C. jejuni is the capsular polysaccharide (CPS), the primary serodeterminant of the bacterium. CPS biosynthetic genes sit within a large, highly variable chromosomal segment flanked by conserved ABC-transporter genes, and variation in these genes gives rise to at least 47 heat-stable (HS) serotypes identified by the classical Penner agglutination system. These 47 serotypes represent approximately 35 distinct capsule types, many of which share more than 97 percent DNA similarity and are therefore clustered into complexes. Beyond its protective role, the capsule mediates serum resistance to complement-mediated killing, facilitates host colonization, and is required for full invasiveness. Epidemiological studies have repeatedly linked certain Penner types, including HS19, HS41, HS23/36, HS4, HS2, and HS1/44, to Guillain-Barré syndrome, with HS19 infection raising the risk of the syndrome at least six-fold compared with other capsular types.

Traditional typing of these two loci has long been cumbersome. Penner serotyping is laborious, the antisera are expensive, and a proportion of outbreak and sporadic strains fail to type due to phase variation or limited antiserum availability. Early molecular alternatives such as restriction fragment length polymorphism analysis, pulsed-field gel electrophoresis, and ribotyping offered improved discrimination but were too costly and complex for routine use. Multiplex PCR assays eventually replaced many serotypic tests, expanding from 17 capsule types to all 47 Penner serotypes, yet PCR-based methods remain culture-dependent, require separate assays for LOS class identification, and do not integrate virulence or antimicrobial-resistance profiling. Moreover, novel capsule loci continue to be discovered in strains from South and Southeast Asia, underscoring the advantage of flexible BLAST-based genomic approaches over PCR schemes with fixed primer sets.

CjejuniTyper addresses this gap as a modular pipeline implemented as a Bash shell script with embedded Python 3 modules. It accepts whole-genome assemblies in FASTA format and executes seven sequential stages: assembly quality control, Mash species confirmation, multilocus sequence typing (MLST), Penner HS capsule typing, LOS class typing, virulence-factor detection, and antimicrobial-resistance profiling. Species confirmation uses Mash v2.3 screening against a reference sketch containing C. jejuni and C. coli genomes, with a shared-hash ratio above 0.5 defining a supported call; C. coli or species-uncertain assemblies remain visible in the output but skip downstream C. jejuni-specific typing. Assembly quality control flags genomes with lengths outside the normal C. jejuni range of 1.3 to 2.0 megabases, GC content outside 27.5 to 33.5 percent, or more than 500 contigs.

Penner prediction in the pipeline replaces antibody-based serology with genomic detection of serotype-associated sequence markers and entire CPS loci. BLASTN searches against a curated marker-gene database evaluate hits across three hierarchical decision tiers, with the most stringent tier requiring at least 99.5 percent nucleotide identity and 80 percent coverage. Full CPS locus alignment provides fallback and supporting evidence, and selected complexes are further resolved using poly-G/C tract analysis for HS23_36c, amino-acid BLASTX analysis for HS8_17c, and in silico PCR confirmation for types including HS29, HS55, and HS58. The pipeline reports 31 conservative HS categories and complexes representing the 47 recognized Penner serotypes, because several serotypes share highly similar CPS loci that cannot be reliably separated from genome assemblies alone. Where sufficient genomic information exists, bracketed subtype predictions such as HS23_36c(HS36) are reported, with an asterisk indicating a predicted genomic subtype rather than a proven serological type.

LOS class assignment relies on a best-hit BLAST scoring system based on the product of percentage identity and fractional coverage, organized into seven decision tiers of decreasing stringency, from STRICT (at least 99.5 percent identity and 96 percent coverage) down to LOOSE (at least 90 percent identity and 60 percent coverage). Close-call rules distinguish the highly similar Classes A and B, and an orf11 BLAST step separates Class A from the mosaic Class R. The pipeline examines codon 51 of Cst-II directly from the query assembly, detecting accessory transferase genes cgtA, cgtB, and wlaN to infer putative ganglioside-mimic biosynthetic potential. A rule-based interpretation engine then combines LOS sialylation status, Penner GBS-associated serotypes, Cst-II allele status, and mimic genotype into a three-tier GBS-associated genomic classification, alongside virulence-factor detection covering cytolethal distending toxin and Type IV secretion system genes and antimicrobial-resistance profiling via AMRFinderPlus, all reported in a single tab-delimited output.

Validation was extensive. LOS typing was evaluated against 617 C. jejuni genome assemblies spanning all 19 implemented LOS classes, including 125 complete genomes and 492 draft assemblies. CjejuniTyper correctly assigned 595 of 617 assemblies, an accuracy of 96.4 percent with Cohen’s kappa of 0.958 and a Matthews correlation coefficient of 0.958, and typing coverage was 100 percent. Penner typing was evaluated against 96 assemblies with verified reference labels covering 14 of the 31 implemented CPS reference categories, collectively representing 27 individual Penner serotypes. The pipeline correctly classified 93 of 96 assemblies, an accuracy of 96.9 percent with kappa of 0.961 and MCC of 0.962, achieving perfect recall for HS41 and HS2. Most errors involved closely related or structurally overlapping loci in fragmented draft assemblies, particularly between the clinically important but computationally difficult LOS Classes A and B.

For the Guillain-Barré syndrome evaluation, the team used 113 retained genomes comprising 89 isolates previously reported from GBS patients and 24 enteritis controls from Bangladesh and international public datasets. Among 84 GBS-associated genomes with published LOS-class assignments, CjejuniTyper produced 83 concordant calls, corresponding to 98.8 percent concordance. In the Bangladesh case-control cohort, HIGH or MODERATE genomic profiles were identified in 34 of 38 GBS-associated isolates and 10 of 24 enteritis controls, corresponding to 89.5 percent sensitivity, 58.3 percent specificity, and 73.9 percent balanced accuracy, with an odds ratio of 11.90 for the association between a positive genomic profile and the GBS clinical group. Across all 89 retained GBS-associated genomes, 81, or 91.0 percent, received HIGH or MODERATE profiles. Targeted analysis showed that four of the ten positive controls contained full-length, high-identity mimicry-pathway proteins, indicating genuine genomic potential rather than analytical error.

The authors are careful to frame the tool’s scope. Because HIGH or MODERATE profiles were also present in some enteritis controls, the integrated classification indicates genomic mimicry-associated potential rather than patient-level clinical prediction; the presence of sialylated LOS and mimicry-associated genes in controls reveals genuine biological overlap between GBS-associated and enteritis isolates. The pipeline also currently supports only the implemented reference LOS classes and CPS types, so isolates carrying previously undescribed or highly divergent loci may be assigned to the closest reference or remain untypeable, and future updates will incorporate newly described reference sequences and expanded validation datasets. Nevertheless, CjejuniTyper represents, to the authors’ knowledge, the first publicly available pipeline that simultaneously performs capsule typing, LOS class assignment, Cst-II allele calling, virulence-gene profiling, and interpretation of GBS-associated genomic markers from genome assemblies. The workflow is freely available on GitHub and archived on Zenodo under an MIT License, designed to run on Linux with a bundled Conda environment, and suited to high-throughput genomic surveillance where numerous assemblies must be typed rapidly without culture-based serology, supporting the ongoing transition from phenotypic to genomic characterization of C. jejuni in clinical and public health microbiology.

Subject of Research: An automated bioinformatic pipeline for in silico typing of Campylobacter jejuni capsule and lipooligosaccharide loci with Guillain-Barré syndrome-associated genomic profiling

Article Title: CjejuniTyper: integrated in silico typing of Campylobacter jejuni capsule and lipooligosaccharide loci with GBS-associated genomic profiling

Article References: Jurić, D., Ferenčak, I., Grginić, A. G., Žmak, L., & Tabain, I. (2026). CjejuniTyper: integrated in silico typing of Campylobacter jejuni capsule and lipooligosaccharide loci with GBS-associated genomic profiling. Frontiers in Microbiology, 17, Article 1943123. https://doi.org/10.3389/fmicb.2026.1943123

Image Credits: AI Generated

DOI: 10.3389/fmicb.2026.1943123

Keywords: Campylobacter jejuni, CjejuniTyper, Guillain-Barré syndrome, lipooligosaccharide, capsular polysaccharide, Penner serotyping, ganglioside mimicry, bioinformatics, genomic surveillance, molecular mimicry, whole-genome sequencing, infectious disease

Pakistan has experienced repeated large dengue outbreaks, including a major epidemic in 2022 that prompted the World Health Organization to issue a formal disease outbreak notice. In such settings, children presenting with fever and new neurological symptoms pose a difficult diagnostic problem. The symptoms of dengue-related brain involvement, ranging from seizures and altered consciousness to weakness and confusion, overlap heavily with those of other viral encephalitides, autoimmune conditions, and metabolic derangements. Magnetic resonance imaging is often the decisive tool, but only if radiologists know which patterns to look for and how to distinguish them from close mimics. The Karachi group, led by Kumail Khandwala and Kiran Hilal, set out to fill that gap by illustrating the full spectrum of dengue-related neuroradiological findings in children and correlating each pattern with the published literature.

The review’s central organizing principle is pathophysiology. Rather than listing findings haphazardly, the authors divide the imaging manifestations of pediatric dengue into three broad mechanistic categories: direct viral invasion of nervous tissue, immune-mediated injury, and reversible edema syndromes. This framework matters because the categories carry different prognoses and demand different clinical responses. Direct viral invasion tends to produce the most severe imaging abnormalities and the gravest illness, while the reversible edema patterns, as their name implies, often resolve completely with supportive care. Immune-mediated disease occupies an intermediate position, sometimes responding dramatically to immunomodulatory treatment. Understanding which category a given scan belongs to is therefore not an academic exercise but a practical step toward appropriate management.

Within the direct-invasion category, the review describes meningoencephalitis, involvement of the deep gray matter nuclei, and rhombencephalitis, which is inflammation centered on the brainstem. The most striking and diagnostically valuable findings in this group are two named signs that have become associated with severe dengue encephalitis. The first is the so-called double doughnut sign, in which symmetric lesions in the thalami develop a central area of necrosis surrounded by a ring of edema, producing a pattern on axial images that resembles two doughnuts side by side. This appearance reflects acute necrotizing encephalopathy, a fulminant form of viral brain injury in which the damage is driven partly by a cytokine storm rather than by the virus alone. The review notes that dengue-associated acute necrotizing encephalopathy is now considered by many investigators to be a true variant of that syndrome rather than a mere mimic, a conclusion supported by a recent systematic review of published cases.

The second named pattern is the Jack-o’-lantern sign, seen in dengue rhombencephalitis. On imaging, the brainstem shows scattered, patchy areas of abnormal signal within the pons that give the structure a carved, hollowed-out appearance reminiscent of a Halloween pumpkin. Brainstem involvement in dengue is uncommon but clinically dangerous, because the pons and medulla control breathing, heart rate, and other vital functions. The review highlights that this sign has been reported to be reversible in some patients who survive the acute illness, which underscores the importance of recognizing it early and providing aggressive supportive care rather than assuming a uniformly fatal course. Distinguishing dengue rhombencephalitis from other causes of brainstem inflammation, such as Listeria infection or other flaviviruses, relies on the clinical context, serological testing, and the specific distribution of lesions.

The immune-mediated category encompasses two related but distinct white matter disorders. The first is acute leukoencephalopathy with restricted diffusion, a condition in which the brain’s white matter shows marked restriction of water molecule movement on diffusion-weighted imaging, indicating acute cytotoxic injury. The second is acute disseminated encephalomyelitis, a post-infectious autoimmune demyelinating syndrome in which the body’s immune response, triggered by the virus, mistakenly attacks the myelin sheaths of its own neurons. The review emphasizes that these two entities can be told apart by their diffusion characteristics and their timing relative to the infection. Acute leukoencephalopathy with restricted diffusion typically appears during the acute phase and shows true restricted diffusion, whereas acute disseminated encephalomyelitis tends to emerge days to weeks after the febrile illness and shows different diffusion behavior along with lesions that may enhance after contrast administration. This distinction has direct therapeutic consequences, because the autoimmune condition is the one that typically warrants corticosteroids or other immunotherapy.

The third category, reversible edema syndromes, includes two entities with reassuring outcomes when properly identified. Reversible splenial lesion syndrome involves a characteristic lesion in the splenium, the posterior portion of the corpus callosum that connects the brain’s two hemispheres. On MRI the lesion appears as a small, round area of restricted diffusion, and, crucially, it typically disappears completely on follow-up imaging as the child recovers. Dengue has been reported as a cause of this syndrome in multiple case reports from Asia and elsewhere. The second, less commonly reported entity in the dengue context is posterior reversible encephalopathy syndrome, a condition in which the parietal and occipital regions of the brain develop vasogenic edema, often in association with severe hypertension, seizures, and visual disturbances. The Karachi group has previously studied pediatric posterior reversible encephalopathy syndrome in depth, examining how blood pressure relates to imaging severity and atypical MRI features, and that expertise informs the current review’s treatment of the dengue-associated form.

Beyond the brain, the review extends its atlas to the spinal cord and peripheral nerves. Dengue-associated myelitis, inflammation of the spinal cord, can produce transverse myelitis with weakness and sensory loss below the affected level, and MRI plays a central role in defining the extent and character of the cord lesion. Guillain-Barré syndrome, the autoimmune peripheral neuropathy that causes ascending weakness and can progress to respiratory failure, has also been increasingly linked to dengue infection, with recent systematic reviews cataloging the clinical characteristics, outcomes, and predictors of severity in these patients. The review stresses that MRI is valuable in differentiating dengue-related myeloradiculopathies from other infectious and inflammatory causes, a distinction that determines whether antiviral, immunomodulatory, or purely supportive strategies are most appropriate.

Perhaps the most practically useful single insight in the review concerns hemorrhage. The authors highlight that intralesional hemorrhagic changes, detected on susceptibility-weighted imaging or gradient recalled echo sequences, particularly within the deep gray nuclei and the brainstem, represent a valuable marker that favors dengue over several viral and inflammatory mimickers. Susceptibility-weighted sequences are exquisitely sensitive to blood breakdown products, and their ability to reveal microhemorrhages in characteristic locations gives radiologists an additional clue that can tip the diagnostic balance in dengue’s favor. In a region where Japanese encephalitis, tuberculosis, and other neurotropic infections circulate alongside dengue, such pattern-recognition tools can meaningfully shorten the path to the correct diagnosis.

The broader significance of the Karachi review lies in its synthesis. By systematically illustrating the full range of pediatric dengue neuroradiology and anchoring each pattern in its pathophysiological mechanism, the authors aim to improve diagnostic confidence among radiologists and clinicians who may encounter only a handful of such cases in a career. As climate change expands the geographic range of the Aedes mosquito vectors and dengue incidence rises globally, the neurological complications of the virus will increasingly be seen outside traditional endemic zones, in emergency departments where familiarity with these imaging signatures is limited. A pattern-based approach, grounded in the double doughnut and Jack-o’-lantern signs, the diffusion characteristics that separate leukoencephalopathy from demyelination, and the hemorrhagic markers that distinguish dengue from its mimics, offers a practical framework for timely recognition and management of one of the more feared complications of a rapidly spreading tropical disease.

Subject of Research: Neuroradiological manifestations of pediatric dengue central nervous system infection on MRI

Article Title: The varying neuroradiological manifestations of pediatric dengue central nervous system infection: a pictorial review from Pakistan with literature correlation

Article References: Khandwala, K., Hasan, S. M., Mateen, S. K., Nadeem, N., & Hilal, K. (2026). The varying neuroradiological manifestations of pediatric dengue central nervous system infection: a pictorial review from Pakistan with literature correlation. Pediatric Radiology. https://doi.org/10.1007/s00247-026-06771-3

Image Credits: AI Generated

DOI: 10.1007/s00247-026-06771-3

Keywords: dengue, pediatric neurology, neuroradiology, MRI, encephalitis, double doughnut sign, Jack-o'-lantern sign, acute disseminated encephalomyelitis, reversible splenial lesion syndrome, Guillain-Barré syndrome, Pakistan, viral infection

At its core, the complement cascade is a proteolytic amplification machine. It can be triggered through three converging routes: the classical pathway, initiated when the C1 complex binds antibody-antigen complexes or other target structures; the lectin pathway, ignited when pattern-recognition molecules such as mannose-binding lectin and ficolins detect carbohydrate motifs on pathogens or damaged cells; and the alternative pathway, which samples surfaces continuously through spontaneous hydrolysis and is stabilized by properdin. All three routes converge on C3, whose cleavage generates the opsonin C3b that tags targets for phagocytosis and the anaphylatoxin C3a that recruits and activates inflammatory cells. Further cleavage of C5 releases the potent anaphylatoxin C5a and assembles the C5b-9 membrane attack complex, a pore-forming structure that can lyse susceptible cells. In host defence, this is a marvel of efficiency. In the nervous system, where many cell types are exquisitely vulnerable to lysis and inflammation, the same machinery can become an instrument of destruction.

What makes complement particularly fascinating in a neurological context is that it is not merely a circulating defence system but an active participant in normal brain physiology. Seminal experimental work has shown that classical pathway components, including C1q and C3, physically tag synapses during postnatal development, allowing microglia to prune weak or inactive connections in an activity-dependent manner. This complement-dependent synaptic sculpting is essential for wiring the developing brain, and related mechanisms continue to influence adult neural circuit plasticity, including microglia-mediated elimination of synapses linked to forgetting. The complement system also contributes to the clearance of apoptotic cells and cellular debris, processes fundamental to maintaining tissue health. These physiological roles carry a sobering implication: any therapeutic strategy that blanketly suppresses complement risks interfering with brain development, synaptic maintenance, and debris clearance, a concern that hangs over much of the current drug pipeline.

In autoimmune neurological disease, aberrant complement activation is now documented with striking consistency. In myasthenia gravis, autoantibodies against the acetylcholine receptor recruit complement to the neuromuscular junction, where the membrane attack complex destroys the postsynaptic membrane, a mechanism established experimentally decades ago and confirmed ultrastructurally by localization of the lytic component C9 at the motor end-plate. Complement activation profiles correlate with disease severity, and eculizumab, a monoclonal antibody that blocks cleavage of C5, demonstrated efficacy in refractory generalized disease in the pivotal REGAIN trial, earning regulatory approval and opening the floodgates for a broader class of anti-C5 agents, including the longer-acting ravulizumab and the subcutaneous peptide zilucoplan, alongside newer C5-targeting candidates such as gefurulimab now in phase 3 testing.

The antibody-mediated demyelinating diseases of the central nervous system tell a similarly compelling story. In neuromyelitis optica spectrum disorder, aquaporin-4-specific IgG1 antibodies bind astrocytic endfeet, fix complement, and generate astrogliotic, necrotic lesions; passive transfer experiments show that immunoglobulin G plus complement reproduces the pathology in animals. Blocking C5 with eculizumab dramatically reduced relapse rates in aquaporin-4-positive patients, and ravulizumab has since replicated these results with a more convenient dosing schedule. The related condition, myelin oligodendrocyte glycoprotein antibody-associated disease, displays its own distinctive complement activation signatures, with recent work showing that activation patterns downstream of C5 cleavage differ between MOGAD and aquaporin-4 antibody-positive neuromyelitis optica, and that complement profiles can predict clinical outcomes. In multiple sclerosis, complement deposition is a prominent feature of lesions, oligodendrocytes are peculiarly susceptible to complement lysis even in the absence of antibody, and growing clinical evidence links circulating complement activation products to structural brain damage, disease severity, and disability progression, including in primary progressive disease. Notably, animal studies reveal that some complement components, such as C5-derived signals, may actually facilitate remyelination, reinforcing the argument for nuanced, pathway-selective modulation rather than indiscriminate shutdown.

In disorders of the peripheral nervous system, complement has moved from suspected accomplice to validated therapeutic target. In Guillain-Barré syndrome, autoantibodies against gangliosides on motor nerve terminals and perisynaptic Schwann cells recruit the membrane attack complex, and complement inhibition protects nerve terminals in murine models. Eculizumab was tested in a large phase 3 trial and, although the primary endpoint was not met, encouraging signals and real-world comparative data for the proximal inhibitor ANX005, which blocks C1q, suggest that early, pathway-targeted intervention may still prove valuable. Chronic inflammatory demyelinating polyneuropathy has emerged as a particularly fertile field: recent complement profiling of sural nerves, together with the demonstration that terminal pathway activation tracks with disease severity, has set the stage for phase 2 studies of the C1s inhibitor riliprubart, with promising early efficacy and safety findings. Multifocal motor neuropathy and IgM anti-MAG antibody neuropathies are likewise being reinterpreted through a complement lens, with the C2-blocking antibody empasiprubart, derived from the ARGX-117 program, advancing through clinical development on the logic that IgM-driven complement activation depends critically on the classical pathway component C2.

Perhaps the most provocative frontier is neurodegeneration. In Alzheimer disease, genetic association studies first implicated complement genes as susceptibility loci, and mechanistic work then showed that C1q and C3 drive early synapse loss in mouse models, with microglia engulfing complement-tagged synapses. Complement C3 deficiency protects aged, plaque-laden mice from neurodegeneration, yet other data indicate that specific complement components exert tissue-protective effects, promoting clearance of amyloid debris and supporting repair. Similarly, in amyotrophic lateral sclerosis, elevations of C5a and the membrane attack complex in patient blood and dysregulation of the cascade in the hSOD1G93A mouse model motivated a randomized trial of ravulizumab, which did not slow disease progression but provided dose-finding and safety data that will inform future, more precisely targeted efforts. These mixed results crystallize the central dilemma of the field: complement is both arsonist and firefighter, and the therapeutic challenge is to extinguish the destructive arm of the cascade while preserving its reparative functions.

The authors of the review emphasize that the existing complement drug arsenal, which includes C5 inhibitors such as eculizumab, ravulizumab, and crovalimab; the C1s inhibitor sutimlimab; the C3-targeting peptide pegcetacoplan; factor B and factor D blockers such as iptacopan and danicopan; C1-esterase inhibitor concentrates; and the C2-blocking antibody empasiprubart, was largely forged in hematology, ophthalmology, and nephrology before being imported into neurology. Expanding these agents to the brain raises distinctive pharmacological hurdles, including the blood-brain barrier, the need for sustained pathway suppression in a compartment with limited drug access, and the infection risks inherent in disabling a key arm of host defence, particularly meningococcal disease in patients receiving terminal pathway inhibitors. Proximal inhibitors that block C1 or C2 confer broader cascade suppression and may better preserve certain distal functions, but they carry their own trade-offs in infection susceptibility and disruption of physiological opsonization and debris clearance.

Looking ahead, Dalakas and Lünemann argue that the future of complement-targeted neurology will depend on systematic, biomarker-guided patient selection. Reliable, disease-specific measures of complement activation, whether from cerebrospinal fluid, blood, or tissue, will be essential to identify which patients are most likely to benefit from proximal versus distal inhibition, and to time intervention before irreversible tissue injury has occurred. As biologics targeting other axes of autoimmunity, from FcRn antagonists and neonatal Fc receptor blockers to B-cell-depleting agents and, increasingly, CAR T-cell therapies, crowd the neurological treatment landscape, complement inhibitors will need to demonstrate not just efficacy but a rational, mechanistically defined place in therapeutic algorithms. What is no longer in doubt is the direction of travel: from a system once studied almost exclusively by immunologists, complement has become a frontier of clinical neurology, and the coming decade will determine how precisely medicine can wield its power without extinguishing its gifts.

Subject of Research: The role of the complement system and complement-targeted therapeutics in autoimmune and neurodegenerative neurological diseases

Article Title: Role of complement and complement-targeted therapeutics in neurological diseases

Article References: Dalakas, M. C., & Lünemann, J. D. (2026). Role of complement and complement-targeted therapeutics in neurological diseases. Nature Reviews Neurology. https://doi.org/10.1038/s41582-026-01261-4

Image Credits: AI Generated

DOI: 10.1038/s41582-026-01261-4

Keywords: complement system, neuroimmunology, myasthenia gravis, neuromyelitis optica, multiple sclerosis, Guillain-Barré syndrome, Alzheimer disease, amyotrophic lateral sclerosis, eculizumab, ravulizumab, membrane attack complex, complement inhibitors