[Electrophoresis of cerebrospinal fluid proteins].
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132 cerebrospinals fluids from patients with degenerative diseases of the central nervous system have been analyzed for protein distribution in agar gel electrophoresis. After subdivision into diagnostically well defined groups these patients were compared with 48 with metabolic and psychiatric diseases and with 79 normal controls. The majority of diagnostic groups showed a tendency to permeability impairment. Other outstanding deviations were not found, except for single cases which were not statistically typical of the groups as a whole. However, the "degenerative type" of proteinogram emphasized in the literature predominated not only in the degenerative groups but also in certain other diseases with destruction of central nervous tissue which do not belong to the degenerative diseases in the strict sense. On the other hand, there are some degenerative subgroups without this "typical" electrophoretic pattern. There would thus appear to be grounds for amending the term "degenerative" into "tissue destroying" or "atrophic type", to avoid misinterpretation.
Cerebrospinal fluid (CSF) total protein, albumin and IgG concentrations were measured in 53 patients with lower back pain syndromes. In the majority of the patients (81 %) the protein values were within normal ranges, a finding contrary to previous studies. In six of 28 patients with acute lumbar disc prolapse and in two of four cases with spinal stenosis, a clearly abnormal protein pattern was observed, while patients who had been earlier operated on for disc prolapse showed normal values. The calculated permeability indexes suggest that the elevation of various proteins is linked with increased permeability across the blood-brain barrier and that the local immunoglobulin synthesis in CNS is lacking. In only one of the cases with an abnormal CSF protein pattern could no evidence of the cause of the pathological finding be observed in subsequent examinations.
The cerebrospinal fluid and serum proteins from 32 healthy individuals have been examined by isoelectric focusing in a pH-gradient from 3.5--11.0. Seventeen normal proteins have been identified by means of crossed immunoelectrofocusing. The pI-values of the main fractions of these proteins have been determined. On crossed immunoelectrofocusing microheterogeneity was observed for all of the proteins except haemopexin, gamma-trace protein of CSF and prealbumin of serum. Differences between serum and CSF were observed for 6 of the proteins. Prealbumin of CSF had a lower pI-value than in serum and showed partial immunological identity with prealbumin of serum. Transferrin of CSF included several components with lower sialic acid contents than in serum. The conversion of C'3-complement from beta-1-C to beta 1-A was slower in CSF than in serum. Qualitative differences between CSF and serum were also noticed for alpha2-macroglobulin and haptoglobin. IgM was not detected in CSF. In CSF the gamma-trace protein was found on isoelectric focusing in one third of the subjects. Two subjects had 2 close tau-fractions and another two had one unidentified band in the anodal IgG-area. The gamma-trace protein did not show any proteolytic activity, nor any resemblance in charge to 4 basic enzymes or with the histones tested.
A sibship originally reported by Friedman and Roy as showing severe mental retardation, strabismus, hyperactive tendon reflexes, lalling speech, and foot deformities was restudied. Three major additional findings were noted. The cerebrospinal fluid protein concentration was increased two to three times above normal in four siblings who were available for study. Radiographs of cranial structures in three siblings showed identical pathologic intracranial calcifications which correspond in distribution to the choroid plexus. The choroid plexus was not demonstrable in one patient when radiolabeled 99m-Tc-pertechnetate was injected without perchlorate. Neuropathologic findings in one sibling included small subcortical heterotopias and atrophy of the choroid plexus with encasement by glial fibrils. These findings denote a new heredofamilial neurologic syndrome associated with mental retardation and a disorder of choroid plexus.
Cerebrospinal fluids (CSF) (N = 365) from patients with non-inflammatory diseases of the central nervous system were analyzed for protein distribution by agar gel microelectrophoresis. After subdivision into diagnostically well defined groups, these patients were compared with 79 normal controls. Most of the diseases investigated were found to follow the "plasma-type" pattern. In some of them the deviations from normal were so extensive that a CSF-protein pattern similar to the "acute-phase reaction" in the serum occurred. Moreover, the following characteristics were found: a considerable increase in total protein and the gamma-globulin fractions in neurinomas; a reproducible increase in the alpha1-globulins in metastases of the central nervous system; and a statistically significant difference of CSF protein findings between male and female patients with protrusion of lumbar intervertebral discs.
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The increased permeability of the blood-brain barrier during acute inflammation of the central nervous system leads to changes of the cerebrospinal fluid (C.S.F.) protein pattern. Initially, in the cases of bacterial meningitis, cellulos acetate electrophoresis revealed decreased prealbumin, albumin and tau-globulin fraktion whereas alpha- and gamma-globulin fractions were found increased. In later stages of purulent inflammation a hydrocephalus occurred in five children, associated with an increased amount of albumin in the C.S.F. Cases of viral meningoencephalitis had a characteristic decrease of prealbumin and increase of gamma-globulin, the lowered prealbumin values were found more often. In three cases of congenital encephalitis pathological patterns of C.S.F. proteins were still found 1--1 1/2 years postpartum. Children with acute peripheral facial palsy and febrile convulsions had a normal C.S.F. protein profile.
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In order to investigate the value of CSF-protein analyses in spasmodic torticollis CSF from six patients with probable organic and two patients with probable psychogenic torticollis was examined by isoelectric focusing and electrophoresis. In all the patients with organic torticollis two pathological CSF-protein fractions were found in the alkaline region on electrofocusing and in four cases aberrant fractions occurred also in the acidic pH range. An increasing number of abnormal fractions were noted during at least the first year after onset of symptoms. Lithium treatment of three patients resulted in a striking decrease of torticollis as well as of the number of abnormal CSF-protein fractions. During placebo treatment of two cases, torticollis and the pathological CSF-proteins recurred. Some observations, including a few previous autopsy findings, might indicate that an encephalitogenic agent is involved in the pathogenesis of organic torticollis. In the patients with psychogenic torticollis the CSF-protein pattern was normal. This investigation supports a recent suggestion that organic and psychogenic torticollis might be distinguished by electrofocusing of the CSF-protein.
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Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. The lack of objective molecular biomarkers limits early diagnosis and personalized treatment. Here, we propose Essence, a benchmarking-validated framework integrating cerebrospinal fluid (CSF) proteomics with traditional and deep learning models to identify robust protein signatures for PD. Using data from two independent cohorts, 1266 high-confidence proteins are quantified, among which 178 exhibit differential abundance between PD and healthy controls (HC). Through systematic benchmarking of ten machine learning algorithms and four neural architectures, the Transformer model consistently outperforms alternatives across multiple feature selection strategies, achieving an area under the receiver operating characteristic curve (AUC) of 1.0000 with only 35 features. Functional analyses of the top-ranked 35 proteins reveal enrichment in neuroinflammatory, synaptic, and oxidative stress-related pathways. Importantly, spatial transcriptomic profiling based on the Allen Brain Atlas shows region-specific expression of these biomarkers in PD-relevant brain structures, including the striatum, subthalamic nucleus, hippocampus, and white matter tracts. This anatomical alignment supports the functional relevance of the identified markers and highlights their potential utility in early-stage diagnosis and mechanistic understanding of PD.
The CSF and sera of 17 patients with meningoencephalitis or encephalitis, 10 with meningitis or meningomyelitis, 5 subjects with postencephalitic sequelae and 2 with arachnoiditis were studied. Diseases involving the intracranial CNS parenchyma were found to give CSF electrofocusing findings differing from those of the other diagnostic subgroups. Differences regarding subfraction patterns of the gamma-globulin region seemed to be influenced of whether supra- or infratentorial structures were affected. The present study seems to indicate that the abnormal CSF-protein patterns found on electrofocusing were not only influenced by temporal but also by spatial factors.