Elevated Cerebrospinal Fluid Protein Levels Research Articles

Chronic Immune Sensory Polyradiculopathy (CISP): A Systematic Review of the Literature

Chronic immune sensory polyradiculopathy (CISP) is a rare inflammatory immune disorder affecting the nervous system, primarily targeting the proximal sensory nerve roots. The condition was first described by Sinreich in 2004. We conducted a systematic review of CISP cases published on PubMed to identify common clinical presentations, along with neurophysiological, radiological, cerebrospinal fluid (CSF), and other findings. Our review included a total of 22 patients from 8 articles. Many patients presented with gait difficulties and sensory ataxia and were found to have normal nerve conduction studies (NCS) and electromyography (EMG) but exhibited characteristic abnormalities in somatosensory evoked potentials (SSEP), elevated CSF protein levels, thickened nerve roots on contrast-enhanced lumbar spine MRIs, and histological changes on nerve root biopsies. Clinical improvement was observed following treatment with steroids and/or intravenous immunoglobulin (IVIG). The study concluded that while CISP is rare, it is an important clinical entity to consider, as accurate diagnosis and appropriate treatment can lead to significant improvements in neurological symptoms and disabilities.

The Initial Clinical and Electrophysiological Characteristics of Different Subtypes of Guillain-Barré Syndrome Diagnosed Based on Serial Electrophysiological Examinations.

We aimed to identify different Guillain-Barré syndrome (GBS) subtypes, demyelination, axonal degeneration, and reversible conduction failure (RCF) as early as possible by analyzing the initial clinical and electrophysiological examinations. This study retrospectively collected GBS patients between October 2018 and December 2022 at Beijing Tiantan Hospital. The diagnostic criteria for the initial electrophysiological study were based on Rajabally's criteria, and the criteria for the serial electrophysiological study were based on Uncini's criteria. All subjects underwent clinical and electrophysiological evaluations at least twice within 8 weeks. A total of 47 eligible patients with GBS were included, comprising 19 acute inflammatory demyelinating polyradiculoneuropathy (AIDP), 18 axonal degenerations, and 10 RCFs. In the RCF group, 40%, 30%, and 30% patients were diagnosed as AIDP, axonal, and equivocal at the initial study, respectively. The AIDP group had significantly higher cerebrospinal fluid (CSF) protein than the RCF (123.8 [106.4, 215.1] mg/dL vs. 67.1 [36.8, 85.6] mg/dL, p=0.002) and axonal degeneration (123.8 [106.4, 215.1] mg/dL vs. 60.8 [34.8, 113.0] mg/dL, p<0.001) groups. The RCF group had significantly lower Hughes functional grades at admission (3 [2, 4] vs. 4 [4, 4], p=0.012) and discharge (1.0 [1.0, 2.0] vs. 3.0 [2.0, 3.0], p<0.001) than the axonal degeneration group and showed significantly shorter distal motor latency (DML), Fmin, Fmean, Fmax, and lower F% than the AIDP group (p<0.05). The early identification of RCF from AIDP had relatively obvious features, including slightly elevated CSF protein levels and normal or slightly prolonged DML and F-wave latencies, contrasting with the apparent elevation and prolongation seen in AIDP. Differentiating RCF from axonal degeneration remains challenging. One potential distinguishing factor is that the motor function in RCF tends to be better than in the latter.

A comparison of infectious and autoimmune meningoencephalitis: Clinical presentation, biochemical markers and MRI findings

Objective: This study investigates distinguishing patterns in lesion distribution, relevant clinical presentation and biochemical markers in MRI to differentiate infective encephalitis (IE) and autoimmune encephalitis (AE). Methods: Retrospective study of adult patients with a confirmed diagnosis of IE and AE admitted to the Neurology unit from January 2012 to December 2020 with MRI Brain. Selected cases with confirmed IE (according to the 2013 Infective Encephalitis Consortium diagnostic criteria) or antibody-positive AE (detection of Neuronal auto-antibody from blood or CSF), coupled by clinical presentation. MRI brain lesion distribution, lobar involvement, enhancement, haemorrhage, vasculopathy and atrophy were analysed. Results: Forty-seven patients (21 IE and 26 AE, respectively) were selected. IE group are older (48.0 ± 16.81) compared to AE (28.4 ± 14.10). Fever and vomiting were significant in IE (p&lt;0.001), whereas psychosis, seizure, movement disorder, and tumour (ovarian teratoma) were significant in the AE cohort. Cerebrospinal fluid (CSF) analysis showed elevated leucocytes with polymorphism and high protein levels in IE (2.081 g/L ± 2.93 vs AE (0.352g/L ± 0.18). MR imaging detected abnormal findings in 61.9% of cases with infectious encephalitis (IE), while 76.9% of cases with autoimmune encephalitis (AE) exhibited normal MRI results. Asymmetrical lesions and inferior frontal lobe distribution (57.1%) were significantly prevalent in IE (p&lt;0.05). Enhancement patterns and haemorrhage were rarely observed in AE patients. Conclusion: IE presented at an older age, with the majority having MRI findings such as asymmetrical lesions, leptomeningeal enhancement, and involvement of medial temporal, hippocampus and inferior frontal cortex. IE clinically presents with fever, vomiting, and elevated CSF leucocytes and protein levels. AE presents at a younger age with seizure, psychosis, movement disorder, tumour (ovarian teratoma). Fewer AE have MRI findings, and if present, tend to be symmetrical in distribution. Lobar involvement in the inferior frontal was the MRI feature that significantly favoured the diagnosis of IE compared to AE. IE and AE have distinct clinical, biochemical, and MRI abnormalities that can be discriminated between the 2 entities.

Autoimmune Nodopathy

Autoimmune nodopathy (AN), a newly established category of autoimmune disease, refers to an immune-mediated neuropathy associated with development of autoantibodies against membrane proteins, including neurofascin 186, neurofascin 155, contactin-1, and contactin-associated protein 1 located in the nodes of Ranvier or paranodes. Subclass analysis of these autoantibodies reveals predominant elevation of immunoglobulin (G4. Patients with AN show clinical and laboratory characteristics such as distal-predominant sensorimotor disturbance, sensory ataxia, poor response to intravenous immunoglobulin, and highly elevated cerebrospinal fluid protein levels. B cell-depletion therapy using an anti-CD20 monoclonal antibody is effective for patients with AN. Autoantibody measurement is beneficial not only for diagnosis but also for deciding treatment strategies for AN.

Clinical characteristics of patients with autoimmune nodopathy with anti-neurofascin155 antibodies.

According to the latest guidelines on chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), patients with CIDP with anti-neurofascin 155 (NF155) antibodies are referred to as autoimmune nodopathy (AN), an autoimmune disorder distinct from CIDP. We aimed to compare the clinical data of patients with AN with anti-NF155 antibodies with those of anti-NF155 antibodies-negative patients with CIDP, and to summarize the clinical characteristics of patients with AN with anti-NF155 antibodies. Nine patients with AN with anti-NF155 antibodies and 28 serologically negative patients with CIDP were included in this study. Diagnosis was made according to the diagnostic criteria in the European Academy of Neurology (EAN)/Peripheral Nerve Society (PNS) guidelines on CIDP published in 2021. Demographics, clinical manifestations, electrophysiological examination, cerebrospinal fluid (CSF) tests, and response to treatment were retrospectively analyzed. Compared with serologically negative patients with CIDP, those patients with AN with anti-NF155 antibodies were younger (p=0.007), had a younger onset age (p=0.009), more frequent ataxia (p=0.019), higher CSF protein levels (p=0.001), and more frequent axon damage in electrophysiology (p=0.025). The main characteristics of patients with AN with anti-NF155 antibodies include younger age and onset age, limb weakness, sensory disturbance, ataxia, multiple motor-sensory peripheral neuropathies with demyelination and axonal damage on electrophysiological examination, markedly elevated CSF protein levels, and varying degrees of response to immunotherapy. Patients with AN with anti-NF155 antibodies differed from serologically negative patients with CIDP in terms of clinical characteristics. When AN is suspected, testing for antibodies associated with the nodes of Ranvier is essential for early diagnosis and to guide treatment.

Toxic-Induced Encephalopathy Following Chemsex in a Young HIV-Positive Male: A Complex Case of Acute Cognitive Impairment with Anterograde Amnesia and Behavioral Alterations.

A broadened clinical spectrum of concomitant complications emerges among the escalating incidence of substance use, particularly within the 'chemsex' context. This case exemplifies the profound neurotoxic repercussions and neurological risk of chemsex in a young HIV-positive male and addresses the multifaceted challenges of such evolving paradigms in substance utilization. After consuming cannabis, poppers, methamphetamine, and cocaine, a 28-year-old HIV-positive male exhibited significant neurological and cognitive impairment. The initial presentation included dysarthria and profound anterograde amnesia. Laboratory findings showed leukocytosis with a PCR of 3mg/dl - elevated cerebrospinal fluid protein levels with no cells. Urine toxicology returned positive for cannabis and amphetamines. A brain CT scan revealed bilateral and symmetrical hippocampi and pale globes hypodensity, indicative of toxic-metabolic encephalopathy. MRI further identified lesions in the globus pallidus, cerebellum, and hippocampi. Following the detection of toxic encephalopathy, Initial neuropsychological was performed screening using the Montreal Cognitive Assessment (MoCA), which highlighted immediate memory deficits. An in-depth neuropsychological assessment conducted 3weeks later included the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV), the Rey Auditory Verbal Learning Test (RAVLT), and tests for visuospatial skills, motor functions, and memory recall. The evaluations revealed pronounced anterograde amnesia, persistent long-term memory inconsistencies, and notable executive function challenges, detailed in Table 1. The detailed analysis of this case underpins the severe neurological consequences that can manifest from heavy substance use. Comprehensive diagnostic evaluations, including neuroimaging and neuropsychological assessments, are crucial in elucidating the full spectrum of substance-induced cognitive impairments. There is an urgent need for enhanced public awareness and preventative measures, especially in the context of chemsex, to bring forth multifaceted health, social, and government implications that modern society must adeptly navigate.

Cerebrospinal fluid protein concentration in patients with lumbar spinal stenosis.

In this study, we examined the impact and degree of lumbar stenosis on cerebrospinal fluid (CSF) protein concentration. In this retrospective study, we analyzed protein concentrations in CSF samples of 61 patients with lumbar spinal stenosis (LSS) obtained during pre-operative myelography. Patients were divided into two groups: those showing no block to contrast (Group A) versus those showing medium block to contrast below the lumbar puncture level (Group B). The CSF protein concentration in Group B (104.3 ± 59 g/dL) patients with medium block was significantly greater than that in Group A (65.1 ± 33 g/dL) patients without medium block. A higher average CSF protein concentration was seen in Group B patients with significant lumbar stenosis versus Group A patients without significant lumbar stenosis. Theoretically, damage to the cauda equina in patients with LSS may cause these elevated CSF protein levels.

Learning from cerebrospinal fluid drug-resistant HIV escape-associated encephalitis: a case report

BackgroundIn the era of antiretroviral therapy (ART), central nervous system (CNS) complications in patients with human immunodeficiency virus (HIV) infection are sometimes associated with cerebrospinal fluid (CSF) viral escape. Here, we reported a case of persistent CNS viral escape with recurrent symptomatic encephalitis, which had ultimate stabilization achieved by a combination of ART adjustment and corticosteroids.Case presentationA 27-year-old man with HIV infection complained of recurrent headaches during the last year. His magnetic resonance imaging (MRI) presented diffused bilateral white matter lesions, and laboratory tests confirmed elevated CSF protein level, lymphocytic pleocytosis, and detectable CSF HIV RNA (774 copies/mL). Plasma HIV RNA was well suppressed with tenofovir, lamivudine, and lopinavir/ritonavir. Prednisone 60 mg once daily was initiated to reduce intracranial inflammation, followed by a good clinical response, with CSF HIV RNA still detectable (31.1 copies/mL). During the gradual tapering of prednisone, his headache relapsed, and booming viral loads were detected in both CSF (4580 copies/mL) and plasma (340 copies/mL) with consistent drug-resistant mutations. Thereupon, prednisone was resumed and the ART regimen was switched to zidovudine, lamivudine, and dolutegravir according to drug resistance tests. Persistent clinical recovery of symptoms, neuroimaging, and laboratory abnormalities were observed in the follow-up visits.ConclusionCSF and plasma HIV RNA and further drug resistance tests should be monitored in HIV-infected patients with neurologic symptoms, as opportunistic infections or tumors can be ruled out. ART optimization using a sensitive regimen may be crucial for addressing CSF viral escape and the related encephalitis.

Comparison of glial fibrillary acidic protein-immunoglobulin G-associated myelitis with myelin oligodendrocyte glycoprotein-immunoglobulin G-associated myelitis.

Glial fibrillary acidic protein-immunoglobulin G (GFAP-IgG)-associated myelitis and myelin oligodendrocyte glycoprotein-IgG (MOG-IgG)-associated myelitis have rarely been compared. Therefore, this study aimed to explore the clinical, laboratory, and imaging features of them to identify the differences. Overall, 14 and 24 patients with GFAP-IgG-and MOG-IgG-associated myelitis, respectively, were retrospectively screened and included in the study. Among the 14 patients with GFAP-IgG-associated myelitis, the condition was more common in males (71.4%), with a median age of onset of 36.5 years, and more common in adults than in children (35.7%). In contrast, among the 24 patients with MOG-IgG-associated myelitis, the condition was equally divided between males and females, with a median age of onset of 9.5 years and more in children (66.7%) than in adults. The median age of onset of GFAP-IgG-associated myelitis was later than that of the MOG-IgG group. Isolated myelitis was rare in both groups. Elevated cerebrospinal fluid (CSF) protein levels were more prevalent in patients with GFAP-IgG-associated myelitis (64.3%) than in those with MOG-IgG-associated myelitis (16.7%) (p < 0.05), whereas patchy gadolinium enhancement of the cerebral lesion site was less common in patients with GFAP-IgG-associated myelitis than in those with MOG-IgG associated myelitis (p < 0.05). Six patients had a combination of other neurological autoantibodies, the specific mechanism of the overlapping antibodies remains unclear. Cerebrospinal fluid analysis and gadolinium enhanced MRI examination may help to distinguish the two kinds of myelitis.

Elizabethkingia meningoseptica Outbreak in NICU: An Observational Study on a Debilitating Neuroinfection in Neonates

Background: Elizabethkingia meningoseptica is an emerging nosocomial pathogen implicated in neonatal sepsis with high mortality and morbidities. However, there is very limited data regarding the characteristics as well as outcomes following this infection, particularly in developing countries. Methods: We conducted a retrospective observational study of all infants with culture-positive Elizabethkingia sepsis as part of an outbreak, to study their clinical and epidemiological characteristics, as well as their antimicrobial susceptibility patterns, using a structured proforma from the neonatal intensive care unit database. Analysis was done using descriptive statistics and predictors of mortality and hydrocephalus were also identified. Results: Of the 21 neonates enrolled, 9 (42.9%) were male, with a mean gestational age and birth weight of 31.7 ± 3.4 weeks and 1320 ± 364 g, respectively. The median (interquartile range) age of onset of illness was 7 (5–12) days. The overall mortality rate was 23.8%, and among survivors, 50% had neurologic complications requiring intervention. Vancomycin and ciprofloxacin were the most used antibiotics for treatment in our series, with a median duration of 26 (17–38) days. On univariate analysis, shock at presentation was significantly associated with increased mortality (P = 0.04) while, seizures (P = 0.04) and elevated cerebrospinal fluid protein levels (P = 0 .01) at onset of illness predicted progressive hydrocephalus in surviving neonates. Conclusion: E. meningoseptica sepsis is associated with high morbidity and mortality. Early diagnosis and prompt initiation of appropriate antibiotics are critical for improving survival and neurodevelopmental outcomes. Though isolation of the organism by environmental surveillance is always not possible, with proper infection control measures, the infection can be controlled.

The effect of double filtration plasmapheresis and corticosteroids on patients with anti-dipeptidyl-peptidase-like protein 6 encephalitis.

Anti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis is a rare condition with varied symptoms including gastrointestinal issues, weight loss, cognitive and mental dysfunction, and hyperexcitability of the central nervous system. We studied five patients with anti-DPPX encephalitis who received immunotherapy, specifically DFPP, at our hospital. We analyzed their clinical symptoms, lab results, electrophysiological and imaging findings, and outcomes with immunotherapy. Patients presented with cognitive dysfunction, tremor, seizures, psychiatric disturbances, and cerebellar and brainstem dysfunction. Magnetic resonance imaging (MRI) showed brain abnormalities in one patient and elevated cerebrospinal fluid (CSF) protein levels in two patients. Antibodies against DPPX were detected in all patients and in CSF in two patients. One patient had antibodies against anti-CV2/contactin response mediator protein 5 (CRMP5). All patients responded well to DFPP and corticosteroids. DFPP may be an effective treatment for anti-DPPX encephalitis. Further research is needed to understand disease progression and evaluate immunotherapy efficacy.

MiR-31-5p as a Potential Circulating Biomarker and Tracer of Clinical Improvement for Chronic Inflammatory Demyelinating Polyneuropathy.

MicroRNAs are endogenous, small noncoding RNA molecules that play a pivotal role in the regulation of gene expression. MicroRNAs are involved in many biological processes such as proliferation, cell differentiation, neovascularization, and apoptosis. Studies on microRNA expression may contribute to a better understanding of the pathomechanism of chronic inflammatory demyelinating polyneuropathy (CIDP) and consequently enable the development of new therapeutic measures using antisense miRNAs (antagomirs). In this study, we evaluated the level of miR-31-5p in the serum of patients with CIDP and its correlation with the miR-31-5p level and clinical presentation and electrophysiological and biochemical parameters. The study group consisted of 48 patients, mean age 61.60 ± 11.76, who fulfilled the diagnostic criteria of a typical variant of CIDP. The expression of miR-31-5p in patient serum probes was investigated by droplet digital PCR. The results were correlated with neurophysiological findings and the patient's clinical and biochemical parameters. The mean copy number of miRNA-31 in 100 μl serum was 1288.64 ± 2001.02 in the CIDP group of patients, while in the control group, it was 3743.09 ± 4026.90. There was a significant positive correlation (0.426) between IgIV treatment duration and miR-31-5p expression. Patients without IgIV treatment showed significantly lower levels of miR-31 compared to the treated group (259.44 ± 304.02 vs. 1559.48 ± 2168.45; p = 0.002). The group of patients with body weight > 80 kg showed statistically significantly lower levels of miRNA-31-5p than the patients with lower body weight (934.37 ± 1739.66 vs. 1784.62 ± 2271.62, respectively; p = 0.014). Similarly, the patients with elevated cerebrospinal fluid (CSF) protein levels had significantly higher miRNA-31-5p expression than those with normal protein levels (1393.93 ± 1932.27 vs. 987.38 ± 2364.10, respectively; p = 0.044). The results may support the hypothesis that miR-31-5p is strongly involved in the autoimmune process in CIDP. The positive correlation between higher miR-31-5p levels and duration of IVIg treatment may be an additional factor explaining the efficacy of prolonged IVIg therapy in CIDP.

Population-Based Evaluation of Total Protein in Cerebrospinal Fluid

ObjectivesTo present a normal range of cerebrospinal fluid (CSF) protein levels in a community-based population and to evaluate factors that contribute to CSF protein level variability. Patients and MethodsSamples of CSF protein were obtained from participants aged 32 to 95 years who underwent lumbar puncture (LP) between November 1, 2007, and October 1, 2017, as part of the Mayo Clinic Study of Aging, a longitudinal, population-based study of residents of Olmsted County, Minnesota. ResultsA total of 633 participants (58.1% male; 99.1% White; mean ± SD age, 70.9±11.6 years) underwent LP with recorded CSF protein level. Mean ± SD CSF protein level was 52.2±18.4 mg/dL (to convert to mg/L, multiply by 10), with a 95% reference interval of 24.0 to 93.4 mg/dL (range, 14.0-148.0 mg/dL). Spinal stenosis and arterial hypertension were associated with higher CSF protein levels on univariable analysis (P<.001). Increasing age, male sex, and diabetes were all independently associated with higher CSF protein levels on multivariable analysis (P<.001). In the 66 participants with repeated LPs within 2.5 years, the coefficient of repeatability was 26.1 mg/dL. Eleven participants (16.7%) had a CSF protein level difference of 20 mg/dL or more between serial LPs, and 4 (6.1%) had a difference of 25 mg/dL or more. There was a trend toward greater CSF protein level variability in patients with spinal stenosis (P=.054). ConclusionThis large population-based study showed that CSF protein level can vary significantly among individuals. Elevated CSF protein level was independently associated with older age, male sex, and diabetes and is higher than listed in many laboratories. These findings emphasize the necessity of evidence-based reevaluation and standardization of CSF protein metrics.

Elevated cerebrospinal fluid protein levels associated with poor short-term outcomes after spinal cord stimulation in patients with disorders of consciousness.

Spinal cord stimulation (SCS) is a promising treatment for patients with disorders of consciousness (DoC); however, the laboratory examinations and different electrodes (permanent #39286 vs. temporary percutaneous #3777, Medtronic, USA) that are associated with postoperative outcomes are unclear. The study aims to study the association between the change in postoperative cerebrospinal fluid (CSF) protein level and improvement in consciousness after SCS in DoC patients and to explore whether different electrodes were associated with elevated CSF protein levels. A total of 66 DoC patients who received SCS treatment from December 2019 to December 2021 were retrospectively analyzed. Patients were grouped according to their elevated CSF protein level. The clinical characteristics of the patients and SCS stimulation parameters were compared. The preoperative sagittal diameter of the spinal canal is the distance from the midpoint of the posterior border of the vertebral body to the midpoint of the posterior wall of the spinal canal at the level of the superior border of C3. The postoperative sagittal diameter of the spinal canal is the distance from the midpoint of the posterior edge of the vertebral body to the anterior edge of the stimulation electrode. Patients with improved postoperative CRS-R scores greater than 3 or who progressed to the MCS + /eMCS were classified as the improved group and otherwise regarded as poor outcome. We found that more DoC patients had elevated CSF protein levels among those receiving SCS treatment with permanent electrodes than temporary percutaneous electrodes (P = 0.001), and elevated CSF protein levels were significantly associated with a reduced sagittal diameter (P = 0.044). In DoC patients receiving SCS treatment, we found that elevated CSF protein levels (P = 0.022) and preoperative diagnosis (P = 0.003) were significantly associated with poor outcomes at 3 months. Logistic regression analysis showed that elevated CSF protein levels were significantly associated with poor outcomes (OR 1.008, 95% CI 1.001-1.016, P = 0.032). The results suggest that reducing the effect of electrode pads on anatomical changes may help improve the outcomes of DoC patients receiving SCS treatment. CSF protein levels are associated with poor postoperative outcomes and whether they are potential biomarkers in DoC patients receiving SCS treatment remain further exploration.

Prognostic Implications of Early Albuminocytological Dissociation in Guillain-Barré Syndrome.

Half of Guillain-Barré syndrome (GBS) present elevated cerebrospinal fluid (CSF) protein levels within 1 week since symptom onset and 80% within 2 weeks. Our objective was to determine the clinical and prognostic implication of albuminocytological dissociation in early GBS. An ambispective cohort study was conducted. Good outcome was considered if the patient was able to walk unaided (Guillain-Barré disability score [GDS] ≤ 2 points) at 3-month follow-up. Patients were classified into two groups: with and without albuminocytological dissociation; we compared clinical and paraclinic characteristics between the groups. We analyzed clinical and electrophysiological factors related to presenting early dissociation through a multivariate model. We included 240 patients who fulfilled Asbury criteria for GBS. On further selection, only 94 patients fulfilled inclusion. Mean age was 45.94 ± 17.1 years and 67% were male. Median time from symptom onset to admission was 5 days (IQR 3-6). Regarding albuminocytological dissociation and electrophysiological variants, we found a significant difference: acute inflammatory demyelinating polyneuropathy (AIDP) [60.6% vs 26.2%, p = 0.002], acute motor axonal neuropathy (AMAN) [21.2% vs 49.1%, p = 0.009] and acute motor sensory axonal neuropathy (AMSAN) [12.1% vs 1.6%, p = 0.05]. We did not observe significant differences in recovery of independent walking in short term between both groups. The presence of conduction block in any variant (OR 3.21, 95% CI 1.12-9.16, p = 0.02) and absence of sural registration (OR 5.69, 95% CI 1.48-21.83, p = 0.011) were independent factors related to early dissociation. Early dissociation (<7 days) is not associated with any particular clinical feature or unfavorable outcome. It is more common to see in AIDP rather than axonal variants.

273. Neurological Involvement Caused by Intracellular Bacteria

BackgroundInfection of the central nervous system is a severe and fatal disease. Causative agents include bacteria, viruses or fungi. Intracellular bacteria are not only overlooked, but also underdiagnosed. We aimed to study the clinical, laboratory and evolutionary features of neurological involvement caused by intracellular bacteria.MethodsWe conducted a retrospective study including all patients hospitalized in the infectious disease department for neurological involvement caused by intracellular bacteria between 1995 and 2020. The diagnosis was confirmed by serology.ResultsWe encountered 76 cases among which 43 were males (56.6%). The mean age was 32±18 years. The revealing symptoms included fever (97.4%), cephalalgia (73.7%), vomiting (64.5%) and arthralgia (51.3%). Lumbar puncture revealed a median white blood cell count of 120[56-340]/mm3. Lymphocytic pleocytosis was noted in 62% of the cases. Elevated cerebrospinal fluid (CSF) protein level was noted in 37 cases (48.7%) with a median of 0.84[0.6-1.37] g/L. Low CSF fluid glucose level was noted in 14 cases (18.4%). There were 70 cases (92.1%) of meningitis and 6 cases of meningoencephalitis (7.9%). The causative agent included Rickettsia species in 47 cases (61.8%), Brucella species in 17 cases (22.4%) and Mycoplasma species in 12 cases (15.8%). Laboratory investigations included elevated C-reactive protein levels (40.7%), thrombocytopenia (32.8%) and increase in hepatic enzyme levels (21%). Anemia was noted in 27 cases (35.5%), leukocytosis in 24 cases (31.5%) and leucopoenia in 6 cases (7.8%). Blood and CSF cultures were positive for Brucella in 2 cases (2.6%) and 5 cases (6.5%), respectively. The mean duration of treatment was 156±94 days for brucellosis cases, 9±4 days for rickettsiosis cases and 10±6 days for Mycoplasma cases. The disease evolution was favorable in 72 cases (94.7%). Four patients were dead (5.3%). Complications were noted in 5 cases (6.5%) and sequelae in 2 cases (2.6%).ConclusionIntracellular bacteria including Brucella, Rickettsia and Mycoplasma species should be considered in front of neurological symptoms. Meningitis with lymphocytic pleocytosis was the most common clinical presentation. An early diagnosis followed by the adequate treatment might avoid complications and death.Disclosures All Authors: No reported disclosures

Cerebrospinal fluid abnormalities in first- and multi-episode schizophrenia-spectrum disorders: impact of clinical and demographical variables

Multiple lines of evidence indicate that immunological and inflammatory alterations contribute at least in a subgroup to the pathophysiology of schizophrenia. In this retrospective chart review, we investigated whether clinical factors contribute to altered cerebrospinal fluid (CSF) findings in schizophrenia-spectrum disorders. Clinical data from electronic medical records of patients with psychotic disorders (ICD-10: F20-F29) who received routine CSF diagnostics at the Department of Psychiatry and Psychotherapy, LMU Munich, Germany, were included. Chi² tests for dichotomous outcomes and independent t tests for continuous outcomes were used to compare differences between groups. A total of 331 patients were included in the analyses (43.2% female and 56.8% male). The mean age was 37.67 years (±15.58). The mean duration of illness was 71.96 months (±102.59). In all, 40% (128/320) were first-episode psychosis (FEP) patients and 60% (192/320) were multi-episode psychosis (MEP) patients. Elevated CSF protein levels were found in 19.8% and elevated CSF/serum albumin ratios (QAlb) in 29.4% of the cases. Pleocytosis was found in 6.1% of patients. MEP patients showed significantly higher mean QAlb compared with FEP patients (t(304.57) = −2.75, p = 0.006), which did not remain significant after correcting for age. QAlb elevation occurred more frequently in men (X2(1) = 14.76, p = <0.001). For treatment resistance, family history, and cMRI alterations, no significant differences in CSF-related outcomes were detected. Our work extends other retrospective cohorts confirming a relevant degree of CSF alterations in schizophrenia-spectrum disorders and shows the difficulty to relate these alterations to clinical and disease course trajectories. More research is needed to develop treatment response predictors from CSF analyses.

Misdiagnosis and diagnostic pitfalls of chronic inflammatory demyelinating polyradiculoneuropathy.

Background and purposeThe aim of this study was to determine the frequency of over‐ and underdiagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and to identify related diagnostic pitfalls.MethodsWe conducted a retrospective study in Dutch patients referred to the Erasmus University Medical Centre Rotterdam between 2011 and 2017 with either a diagnosis of CIDP or another diagnosis that was revised to CIDP. We used the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) 2010 diagnostic criteria for CIDP to classify patients into three groups: overdiagnosis, underdiagnosis, or confirmed diagnosis of CIDP. Clinical and laboratory features and treatment history were compared between groups.ResultsA referral diagnosis of CIDP was revised in 32% of patients (31/96; overdiagnosis). Of 81 patients diagnosed with CIDP, 16 (20%) were referred with another diagnosis (underdiagnosis). In the overdiagnosed patients, 20% of muscle weakness was asymmetric, 48% lacked proximal muscle weakness, 29% only had distal muscle weakness, 65% did not fulfil the electrodiagnostic criteria for CIDP, 74% had an elevated cerebrospinal fluid (CSF) protein level, and 97% had another type of neuropathy. In the underdiagnosed patients, all had proximal muscle weakness, 50% had a clinically atypical CIDP, all fulfilled the electrodiagnostic criteria for CIDP, and 25% had an increased CSF protein level.ConclusionOver‐ and underdiagnosis of CIDP is common. Diagnostic pitfalls include lack of attention to proximal muscle weakness as a diagnostic hallmark of CIDP, insufficient recognition of clinical atypical phenotypes, overreliance on CSF protein levels, misinterpretation of nerve conduction studies and poor adherence to electrodiagnostic criteria, and failure to exclude other causes of polyneuropathy.

Neonatal Ureaplasma parvum meningitis complicated with subdural hematoma: a case report and literature review

BackgroundNeonatal meningitis is a severe infectious disease of the central nervous system with high morbidity and mortality. Ureaplasma parvum is extremely rare in neonatal central nervous system infection.Case presentationWe herein report a case of U. parvum meningitis in a full-term neonate who presented with fever and seizure complicated with subdural hematoma. After hematoma evacuation, the seizure disappeared, though the fever remained. Cerebrospinal fluid (CSF) analysis showed inflammation with CSF pleocytosis (1135–1319 leukocytes/μl, mainly lymphocytes), elevated CSF protein levels (1.36–2.259 g/l) and decreased CSF glucose (0.45–1.21 mmol/l). However, no bacterial or viral pathogens in either CSF or blood were detected by routine culture or serology. Additionally, PCR for enteroviruses and herpes simplex virus was negative. Furthermore, the CSF findings did not improve with empirical antibiotics, and the baby experienced repeated fever. Thus, we performed metagenomic next-generation sequencing (mNGS) to identify the etiology of the infection. U. parvum was identified by mNGS in CSF samples and confirmed by culture incubation on mycoplasma identification medium. The patient’s condition improved after treatment with erythromycin for approximately 5 weeks.ConclusionsConsidering the difficulty of etiological diagnosis in neonatal U. parvum meningitis, mNGS might offer a new strategy for diagnosing neurological infections.

Clinical features of anti-leucine-rich glioma-inactivated 1 encephalitis in northeast China

AimTo examine the clinical characteristics, laboratory tests, imaging and electroencephalography presentation, treatment, and prognosis of anti-leucine-rich glioma-inactivated 1 (anti-LGI1) encephalitis and improve the awareness of this disease. MethodWe performed a retrospective analysis of the clinical data of 41 patients who were diagnosed with anti-LGI1 encephalitis. Their clinical characteristics, laboratory tests, and imaging and electroencephalography data were collected, and the treatment results and prognosis were evaluated. The modified Rankin Scale (mRS) was used to evaluate neurological function. ResultsA total of 41 patients were included in the study, the average follow-up time is 33.0 months.The initial symptoms included cognitive impairment (n = 16, 39.0%),faciobrachial dystonic seizures (FBDS) (n = 12, 29.3%), grand mal seizures (n = 5, 12.2%) hallucinations (n = 4, 9.8%), loss of consciousness (n = 2, 4.9%), nausea and vomiting (n = 1, 2.4%),and head discharge-like sensation and radiate one limb (n = 1, 2.4%). There were 20 and 21 patients in the good (mRS ≤ 2) and poor (mRS > 2) prognosis groups, respectively. In the good prognosis group, the initial symptoms included faciobrachial dystonic seizures (FBDS) (n = 6, 30.0%), cognitive impairment (n = 6, 30.0%), hallucinations (n = 4, 20.0%), grand mal seizures (n = 3, 15.0%), loss of consciousness (n = 2, 10.0%), and nausea and vomiting (n = 1, 5.0%). There were 10 patients with hyponatremia. Magnetic resonance imaging (MRI) showed limbic system involvement in 12 patients (60.0%).17 patients (85.0%) recovered, 2 (10.0%) showed significant improvement, and 1 (5.0%) died after a mean follow-up period of 36.9 months. In the poor prognosis group, the initial symptoms included FBDS (n = 6, 28.5%), cognitive impairment (n = 10, 47.6%), grand mal seizures (n = 2, 9.5%), and electric shock-like sensation in the left limbs (n = 1, 4.7%). There were 20 patients with hyponatremia. MRI showed limbic system involvement in 11 patients (52.4%). 11 patients (52.4%) recovered, 8 (38.1%) showed significant improvement, and 2 (9.5%) died after a mean follow-up period of 29.0 months. ConclusionsThe clinical characteristics of anti-LGI1 encephalitis include hyponatremia, FBDS, epileptic seizures, hallucinations, cognitive impairment, and loss of consciousness, while the rarely seen characteristics are nausea, vomiting, and other autonomic dysfunctions and electric shock-like sensation. The appearance of hallucinations often indicates a good prognosis.Hyponatremia and elevated cerebrospinal fluid protein levels can be used as indicators that affect the prognosis of patients.Limbic system involvement has nothing to do with prognosis.Attention should be paid to early diagnosis and timely first-line immunotherapy.