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We report the case of a 12-year-old boy presenting with acquired horizontal nystagmus, headaches, and vertigo. CT, MRI, viral tests, and the Lyme disease test were at first negative. We made the diagnosis of neuroborreliosis based on a repeated Lyme disease test and lumbar puncture revealing intrathecal synthesis of specific antibodies. Adjusted antibiotic treatment led to complete disappearance of symptoms. Lyme borreliosis is difficult to diagnose and should be sought in case of unusual neuro-ophthalmic signs, especially in children., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Introduction: Multiple sclerosis and other inflammatory diseases of the central nervous system produce various and nonspecific symptoms. The diagnosis of these diseases is ultimately a clinical decision, although examination of cerebrospinal fluid (CSF) and other complementary tests such magnetic resonance imaging (MRI) and evoked potentials can be contributive. One important aspect of these diseases is intrathecal synthesis of immunoglobulins., Patients and Methods: In order to determine the contribution of CSF/serum immunofixation to the diagnosis of inflammatory diseases of the central nervous system, we conducted a retrospective study in the biochemistry laboratory of the military instruction hospital Mohammed V. 363 CSF/serum samples were collected over a period of four years., Results: Immunofixation was less sensitive than MRI for the diagnosis of inflammatory neurological disease (44% vs 87%), but was much more specific than MRI (97% for immunofixation vs 38%). The positive predictive value was higher that for MRI (85% vs 40%). The negative predictive value (80%) was close to that of MRI (86%). The bivariate analysis showed that immunofixation results could be predicted from clinical findings and complementary test results such as the index of Link, syphilis serology in CSF, and MRI., Conclusions/discussion: Semi-automatic Hydrasys immunofixation of CSF IgG is a technique exhibiting excellent diagnostic and analytical performance for the diagnosis of inflammatory neurological diseases., (Copyright © 2010. Published by Elsevier Masson SAS.)

We report the case of a sixty-eight years old patient, who was admitted to the emergency for paresthesis associated with dysarthra and speech complaints. Neuroimaging revealed the presence of stenosis caused by arteritis. The notion of history of syphilis infection led to diagnosis of neurosyphilis. Diagnosis is difficult due to its clinical polymorphism and requires using several tests in the cerebrospinal fluid (CSF) because infection involving the central nervous system. Neurosyphilis is diagnosed by finding elevated cell count (80 leukocytes/mm3), high protein level (1.07 g/L) and positive IgG oligoclonal bands. In addition CSF and blood should be titrated with the VDRL and TPHA tests which are difficult to interpret. The diagnosis of active neuro-syphilis requires positive, non specific and specific inflammatory tests.

Introduction: We report the magnetic resonance imaging (MRI) findings in a case of neurosyphilis revealed by the involvement of two cranial nerves., Case Report: A 41-year-old man developed a right cochleovestibular and left trigeminal neuropathy, associated with high serum titers of VDRL and TPHA, high titers of TPHA in the cerebrospinal fluid (CSF) and several CSF oligoclonal IgG bands. On MRI, hypertrophy and gadolinium contrast enhancement of these cranial nerves were associated with several supratentorial cortical nodules surrounded by marked cerebral edema, corresponding to syphilitic gummas. One of these cortical nodules was biopsied. Microscopic examination showed lesions of meningoencephalitis with necrosis and granulomatous vasculitis. After penicillin therapy, the serum VDRL titers and the MRI abnormalities disappeared, a partial clinical recovery was observed and a significant reduction of the serum TPHA titers was found., Discussion: Such MRI abnormalities are not specific and can be observed in various tumoral, auto-immune and infectious diseases. They can also mimic neurofibromatosis type II. Cranial nerve involvements in neurosyphilis can result from nerve inflammation in basal meningitis, nerve ischemia in meningovasculitis or from compression by an adjacent gumma. In our case, the cranial neuropathy was related to a mixed meningovascular and parenchymatous form of neurosyphilis.

Introduction: Central nervous system manifestations represent 0.54 to 8% of neurological complication in Lyme disease., Observation: A 78-year-old woman presented a severe meningo-encephalitis with visual disorders (agnosia, alexia) progressing towards coma. Cranial magnetic resonance imaging revealed large areas of hypersignal T2 in the white matter of the lower, parieto-occipital lobes and left temporal lobe. The cerebrospinal fluid (CSF) contained 16 then 293 white corpuscles/mm3 of lympho-monocytes, increased protein level from 2.67 to 5.83 g/l and an increase in IgG index with oligoclonal distribution of IgG. Serological Elisa analysis for Lyme disease was slightly positive in blood (confirmed by western blot) but clearly in the CSF (IgG and IgM). Treatment with ceftriaxone followed by methylprednisolone provided clinical improvement 3 months later., Discussion: Acute meningo-encephalitis is often benign, protein-like and of good prognosis: the gnosic visual disorders with posterior leukoencephalopathy are unusual. A blood level of specific antibodies slightly positive on Elisa at the early stage of the infection warrants confirmation by Western blot in the blood and by Elisa in the CSF. Additional corticosteroid therapy may be required in the severe forms that evoke acute disseminated encephalomyelitis.

The analysis of the cerebrospinal fluid is the only biological test included in the diagnostic criteria for MS. A search for intrathecal IgG synthesis by isoelectrofocussing should always be performed when the cerebrospinal fluid is analyzed for a possible diagnosis of MS. Intrathecal IgG synthesis is detected in about 95 p. 100 of MS cases. However, it is not specific for MS and only signs the inflammatory nature of the nervous system lesions. In our opinion, analysis of the CSF should be proposed systematically for primary progressive MS, in most cases of monosymptomatic demyelinating syndromes, and according to the clinical context and the result of the MRI analyses in the remaining forms. To date, no prognostic criteria can be drawn from the analysis of the CSF. Other biological tests can be performed in order to eliminate other diagnosis. These tests only have a great interest in atypical forms of the disease.

The clinical and demographic characteristics of 86 Brazilian patients with clinically definite multiple sclerosis (MS) were compared to the cerebrospinal fluid (CSF) findings. The disease course was relapsing-remitting in 71% and chronic progressive in 29% of the cases. The IgG index was increased in 76% in the chronic progressive status and 46% and 49% during the bout and remission, respectively (p < 0.005). Only 36% of the MS patients using corticosteroids had increased IgG index, in comparison to the 64% of the patients without immunosupressive treatment. Oligoclonal IgG bands were detected in the CSF of 77% and 88% of the MS corticosteroids users and non-users, respectively. The quantitative study of intrathecal synthesis of IgG contributes to demonstrate the immunological differences between the two forms of MS, the relapsing-remitting and the chronic progressive. The treatment with corticosteroids decreases quantitatively the intrathecal synthesis of IgG but not the presence of oligoclonal bands.

Intrathecal immunoglobulin synthesis is observed in more than 90% of all cases of multiple sclerosis, producing a specific CSF IgG oligoclonal electrophoretic pattern. The consensual method used as reference is isoelectric focusing (IEF). We developed a new CSF Ig analysis method by immunofixation (IF). The method includes an immunoenzymatic detection step performed directly on the gel allowing the use of unconcentrated CSF and avoiding the blotting step. The reliability of this method was established by the analysis of 210 CSF/serum pairs including defined, probable and possible MS, other inflammatory CNS diseases and controls (noninflammatory CNS diseases and peripheral nervous system diseases). Intrathecal IgG synthesis was detected in 95.5% of defined MS cases. The specificity for CNS inflammatory diseases including MS diagnosis, evaluated by comparison with controls, was 98.8%. This new method is quicker and visual interpretation is easier than with IEF. It is a semi-automated method that should be considered for standardization of CSF IgG analysis.

A retrospective study was carried out at the Neurological and Neurosurgical Hospital of Lyon in order to evaluate the interest of detecting IgG oligoclonal bands by isoelectric focusing with IgG immunorevelation for the early diagnosis of multiple sclerosis (MS). Patients have been grouped according to their disorders: multiple sclerosis (281 cases), definite (182 cases) and possible (99 cases), others inflammatory neurological diseases (63 cases), various non-inflammatory neurological disorders (180 cases) and indefined neurological disorders (664 cases). The following examinations were performed: CSF cell count and cytology after concentration and cytocentrifugation, CSF and serum determination of albumin and IgG with CSF/serum ratios, agarose gel electrophoresis and isoelectric focusing of oligoclonal IgG. The technique used was isoelectric focusing using agarose gel, transfer onto PVDF membrane and then IgG immunorevelation with biotinylated anti-human IgG antibodies. Isoelectric focusing with IgG immunorevelation is the most sensitive (94%) and specific (96%) technique. Isoelectric focusing with immune detection can be recommended as the most efficient test (gold standard) for the detection of chronic CNS inflammation.

Though the global course of the disease is well known when considering large cohorts of patients, it is rather difficult to make a prognosis for a given patient. It is essential however to predict the course of the disease as early as possible in order to be able to give the patient the right treatment at the right time. Age at disease onset is one of the most important clinical predictive factors, as this has been proved by various analyses. The earlier the disease onset, the better the prognosis. The inaugural symptom of optic neuritis, the long interval between the first two relapses, a remitting form at onset are predictive factors of a good evolution. A normal brain magnetic resonance imaging performed on the occasion of a first isolated sign of the central nervous system is the marker of a good prognosis. Conversely, the presence of oligoclonal bands in the cerebrospinal fluid and the increase of IgG index increase the risk of occurrence of a second relapse. The new techniques of magnetic resonance imaging and the exhaustive initial clinical examination using several classifications of disability will allow a better prognosis for a given patient.

Thirty-four HIV-1-infected in-patients of the Hôpital Central des Forces Armées Congolaises, Brazzaville, Congo, hospitalized for suspected cerebral toxoplasmosis, have been evaluated for integrity of the blood-brain barrier, intrathecal synthesis of total IgG, toxoplasmic serology in blood and cerebrospinal fluid, and for intrathecal synthesis of IgG to Toxoplasma gondii. An empiric scale to gauge the possibility of clinical cerebral toxoplasmosis was used to classify the patients (+, +2, +3). Only an intrathecal synthesis of IgG to Toxoplasma gondii was found to be associated with suspected cerebral toxoplamosis: it was found in about 80% of patients, and more frequently in patients with a higher probability of disease. In contrast, alteration of the blood-brain barrier, intrathecal synthesis of total IgG and toxoplasmic serology in blood as well as in cerebrospinal fluid were not associated with suspected cerebral toxoplamosis. Taken together, these findings confirm that intrathecal synthesis of antitoxoplasmic antibodies of IgG isotype occurs in cerebral toxoplasmosis. Demonstration of intrathecal synthesis of antitoxoplasmic IgG antibodies could be used to confirm clinical diagnosis of cerebral toxoplamosis, especially in an African context, where sophisticated laboratory facilities are often lacking.

The stage of human African trypanosomiasis (HAT) is important to define precisely as far as it is directly related to the type of treatment used. The beginning of the neurological involvement is difficult to find out because there is no known specific clinical or biological sign. This study is trying to look for a precise marker and has been realized in Congo. 70 subjects with parasitologically confirmed HAT and 70 controls are included. The stage of HAT is determined according to the classical definition on the field using the cerebrospinal fluid (CSF) cell count: less than 5 cells/microliters for the first stage (P1), more than 5 cells/microliters for the second stage (P2). The blood analysis has included: glucose, urea, creatinine, sodium, potassium, calcium, chloride, phosphorus, uric acid, total bilirubin, unconjugated bilirubin, total cholesterol, triglycerides, total proteins, aspartate aminotransferase, alanine aminotransferase, creatinine phosphokinase, alkaline phosphatase, gamma-glutamyltransferase, immunoglobulins M and G, C3c fraction of complement, transferrin, seromucoid alpha 1, haptoglobin and albumin. In CSF we have analyzed IgM, IgG, protein levels and the bloodbrain barrier (BBB) impairment. The comparison between the subjects and their controls, the subjects in P1 and in P2, the CSF cell count and the other CSF alterations show the interest of the IgM level in CSF and the BBB impairment to identify subjects in P2. However there is a low gradation in the biological disturbances and not a precise threshold point. Nevertheless it seems reasonable to raise the CSF cell count level to 20 cells/microliters to define the beginning of the nervous involvement.

Unique physiological and immunological features of the brain, as previously presented, explain the limitation of local inflammatory reactions and the existence of intrathecal specific IgG production. In addition, some parasitic factors of recent knowledge are induced during neurocysticercosis, which could be involved in vivo in a modulation of the immune response by larval products (a soluble RNA-peptide, some metacestode surface sphingoglycolipids). These recent findings lead us to make a critical review of the antigenic profiles obtained by enzyme-linked immunoelectrotransfer blot (EITB) on samples collected from patients suffering from simple or multiple neurocysticercosis.

Cerebral toxoplasmosis and cytomegalovirus (CMV) infection are very frequent in AIDS. Biological markers of toxoplasmosis and CMV were studied in blood and cerebrospinal fluid (CSF) of 121 HIV-positive and 35 HIV-negative patients in the Central Hospital of the Congolese Army in Brazzaville. In the case of clinically suspected cerebral toxoplasmosis, the simultaneous presence of specific IgG antibodies in the blood and in the CSF can be considered as having complementary diagnostic value (PPV = 63.3%, NPV = 89.9%). The symptomatology of AIDS is very polymorphous and includes various etiological factors; as a result it is very difficult to estimate the responsibility of cytomegalovirus in the absence of positive viral culture, even with the simultaneous presence of specific IgG antibodies in the blood and CSF (PPV = 75.7%, NPV = 54.6%).

In a study carried out in Gabon, antibodies against the treponema were looked for in the cerebrospinal fluid (CSF) in 13 children with active congenital syphilis (presence of specific IgM antibodies) and in 7 children with positive serologic reactions reflecting transplacental passage of maternal antibodies. Serologic reactions used included the VDRL test, the TPHA test, and the FTA-ABS IgG and IgM tests. Among the 13 children with syphilis, 7 had a positive FTA-ABS IgG test in the CSF without correlation with severity of clinical features, CSF protein levels or CSF cytologic findings. The TPHA test was positive in only four children and the VDRL test was always negative. Passage of antibodies into the CSF is possible (1 case in this study after treatment of the mother), but TPHA is helpful in developing countries of research of neurosyphilis.

CSF immunological reactions are classified in 5 patterns, considering the level of CSF albumin and the percentage of CSF-IgG. The 5 patterns are: 1) normal, 2) inflammatory (pure local synthesis of IgG), 3) two types of trasudates (inflammatory or not) when blood-CSF exchanges increase, 4) meningitis if a transudate is associated with local IgG synthesis. The distinction between transudate and meningitis needs the determination of serum IgG. This classification better than the classical ratios, defines the immunological status of a neurological patient in the different phases of his disease. It determines the frequency of the 5 immunological patterns for each nervous disease and the signification of any antibody detected in the CSF. It proposes a common language between the different laboratories and overall, between biologists and clinicians.

Cerebrospinal fluid (CSF) protein values were measured in 652 children between the ages of 1 day and 17 years, allowing the authors to define the dynamics of the blood-brain barrier under normal conditions and during inflammation of the nervous system. The ratio of CSF albumin/serum albumin (whose upper limit was 0.65 in the study) was the best sign of alteration of blood-brain barrier permeability. The CSF IgG level, whose upper limit was 0.85 (for serum IgG between 10 and 14 g/l) is the most useful criterion for detecting an intra-thecal synthesis of IgG. Six patterns of CSF proteins are defined on the basis of immunochemical and electrophoretic studies. The ratio of CSF albumin/serum albumin and the CSF IgG level must be compared to the electrophoretic pattern of CSF proteins in order to better characterize one aspect of the blood-brain barrier under normal and pathologic conditions of the central nervous system.

Intrathecal IgG synthesis has been studied in neurological patients by both quantitative and qualitative methods. An elevated correlation was found between IgG/Albumin quotient, IgG-Index and IgG SYN: moreover the appearance of oligoclonal IgG bands in CSF seems clearly related to high IgG Index values, as observed by statistical analysis. Nevertheless oligoclonal pattern in CSF is always present in diseases associated with immunological abnormalities, while quantitative parameters may be found elevated also in the diseases without a clear immunological disturbance. The authors stress the great importance of CSF examination by Isoelectric Focusing in the evaluation of intrathecal IgG synthesis in multiple sclerosis.

Intrathecal synthesis of immunoglobulins can be proved by means of two methods: quantitatively by immunoglobulins titration in CSF, the results expressed with several ratios; qualitatively by demonstration of oligoclonal distribution of gammaglobulins. IEF is the most sensitive of the qualitative methods. From a technical point of view Agarose Isoelectrofocusing seems to be a better method than polyacrylamide isoelectrofocusing and permits, when the interpretation is difficult, immunofixation into the gel. The authors report the results of a comparative study between the evaluation of the IgG Index and agarose isoelectrofocusing of 281 CSF divided into 113 CSF from patients with Multiple Sclerosis (MS) and 168 CSF from patients with other neurological diseases (OND). Sensitivity of IEF was higher than IgG index to prove intrathecal IgG synthesis: in the group of patients with MS, 91 p. 100 of CSF were abnormal instead of 72 p. 100 of IgG Index. In the group of patients with OND, abnormalities in IEF were low (5 p. 100) but the number of inflammatory diseases was poor. These results were similar with the findings of many authors using the same methods. In our opinion, IEF is the best technique which a specialized laboratory can use in routine to prove an immunoglobulin intrathecal synthesis.

The restriction of heterogenicity of immunoglobulins G (IgG), or oligoclonal distribution, in the cerebrospinal fluid (CSF) can be observed after electrophoresis or electrofocalization, the IgG nature of each oligoclonal band being confirmed by subsequent immuno-electrophoresis. Using immunofixation, the oligoclonal bands can be visualized and characterized simultaneously, but requires previous concentration of the CSF, which is a source of error. The technique of radioimmunofixation, here described, allows the study of IgG with 20 microliters of non-concentrated CSF. It demonstrates that the oligoclonal characteristic is present in normal CSF and is a more quantitative than qualitative feature. Preliminary results show that the method can be applied to the study of all CSF proteins. By using a viral antigen labelled with I-125, for example, it should be possible to reveal and visualize the antibody activity of each oligoclonal band and to determine whether the quantitative increase in an oligoclonal band corresponds to a definite antigenic stimulation.

The authors compared 9 cases of myeloma and 2 cases of Waldenström's disease with 10 cases of benign monoclonal gammapathies. None of the patients (except one) had neurological involvement; one patient hab diabetes. The study was focused on the immunoglobulins and proteins in the CSF. The following observations were made: - The CSF protein was raised in 8 out of the 11 malignant gammopathies and in 5 out of the 10 benign gammopathies; - An identical monoclonal protein was found in the CSF and serum in all the cases of malignant gammopathies. In the cases considered to be benign, the results were less concordant: one IgM lymphoma had normal CSF; three IgG dysglobulinemias had different immunoglobulins proteins in their CSF: - The mean CSF immunoglobulin level was much higher in the myeloma patients than in the benign gammopathies; - A number of findings suggest intrathecal secretion (at least in the malignant gammopathies). This is also true in a good number of the benign gammopathy cases. Direct tumoural invasion of the CSF may be more common than generally supposed. However, the study of CSF immunoglobulins alone does not establish the diagnosis of malignant dysglobulinemia. Nevertheless, the authors consider that the finding of intrathecal secretion of immunoglobulin, especially in patients with a discordance in FAB and FC fractions, should lead to a closer follow-up of these patients.

Titration of IgG, albumin, and specific antibodies, both in serum and CSF, during the course of a Candidal meningoencephalitis allowed to demonstrate intrathecal synthesis of specific IgG antibodies against C. albicans.

Cerebrospinal fluid, G, A, M, immunoglobulins, alpha-2-macroglobulin and ceruloplasmin levels were determined by a nephelometric Laser method of a control group of 21 adult patients strictly suffering from a "slipped disc" disease. The same CSF parameters were studied on a second group of 90 patients including adults and children with normal CSF proteins levels (< 500 mg per liter). Normal values were established according to the different age groups. Results were given in milligrams per liter and nanomols per liter.

The authors describe various applications of an immunoblot technique which allows the qualitative determination of the specific antibody activity of oligoclonal IgG intrathecally synthesized in infectious diseases of the nervous system. After dilution of sera to the same IgG concentration as the paired CSF samples, 10 microliters of both fluids are applied side by side on agarose gel plates and isoelectrically focused. Precipitated IgG or specific IgG antibodies are then blotted onto a nitrocellulose sheet previously coated with either a rabbit anti-IgG antiserum or the antigen under study, respectively. The immunoblot is successively incubated with biotinylated anti-IgG antiserum and with the streptavidin-biotin-peroxidase complex before staining with 4 chloro-1-naphthol. This method was applied to samples from patients with subacute sclerosing panencephalitis, herpetic encephalitis, meningoradiculitis due to Herpes Zoster, neuro-AIDS, neurobrucellosis, meningoradiculitis or encephalomyelitis due to Borrelia burgdorferi, and tuberculous meningitis. In each case, specific oligoclonal IgG antibodies, superimposed or not on a diffuse polyclonal synthesis were detected in the CSF, but not, or more faintly, in the corresponding serum. This was taken as evidence for an intra-thecal synthesis of these antibodies. In contrast, when a "mirror effect" was observed, i.e. similar oligoclonal bands in both serum and CSF after dilution at the same IgG concentration, an intra-thecal synthesis was ruled out.

Serological monitoring was performed in 13 cases of herpetic encephalitis (one infant and 12 adults). Samples taken simultaneously from blood and cerebrospinal fluid (CSF) were tested before and after initiation of antiviral treatment. Antiherpesvirus (anti-HSV) antibodies were assayed by an ELISA method. The state of the blood-brain barrier was controlled by assaying other antiviral antibodies. Immune response was studied during the 3-to-4 weeks of the course of the infection. Anti-HSV IgG levels in CSF increased markedly after 12 days. At the same time, antibody serum/CSF ratios dropped below a value of 20, indicating intrathecal secretion of the antibody. Based on results in monitoring these 13 cases, it may be suggested that 3 samples of serum and CSF are required to confirm the herpetic etiology, including 2 samples taken during the second week of the course of encephalitis.

The purpose of this study (about 187 adult psychiatric patients) is to investigate correlations between "organic brain syndrome" (vascular or abiotrophic) and values of CSF proteins (technique of two-dimensional immunoelectrophoresis). The authors show positive correlations between 'vascular' brain syndrome and increase of one alpha 2 globulin, between 'abiotrophic' brain syndrome and decrease in all globulins, the importance of brain damage and increase of IgG/albumin ratio.

Cerebrospinal fluid and serum immunoglobulins were studied in 76 patients with acute meningitis of various aetiologies. This comparative study showed that the increase of CSF immunoglobulin levels was related to important modifications of the permeability of the blood-brain barrier (especially in case of bacterial meningitis) or to a local in situ production (particularly in case of "viral" meningitis). Results obtained allow us to draw a different biochemical pattern in purulent meningitis and acute lymphocytic meningitis.

Intrathecal synthesis of immunoglobulins is analyzed by two methods: quantitatively by immunoglobulin titration (IgG index) in cerebrospinal fluid (CSF) and qualitatively by demonstration of oligoclonal distribution of gammaglobulins. The authors report the results of a comparative study evaluating the IgG index and agarose electrophoresis versus electrofocusing. Sensitivity of electrofocusing was higher than the IgG index of standard agarose electrophoresis. Electrofocusing is the best method of proving intrathecal synthesis of immunoglobulins. Although oligoclonal bands are a useful aid in the diagnosis of multiple sclerosis, they indicate an immunological response but are not diagnostic for a particular disease.

ELISA detection of specific antibodies in the serum (IgG) and cerebrospinal fluid (IgG, IgM and IgA) was evaluated in 28 patients. Diagnosis of cerebral cysticercosis and evaluation of disease activity was based on CT scan findings. Specific IgG antibodies were found in the serum in 83.3% of patients with active disease and 10% of those with inactive disease. Cerebrospinal fluid tests evidenced specific antibodies in all patients with active disease and none of the patients with inactive disease. The specific CSF antibodies were IgG (94.4%), IgM (66.6%) or IgA (66.6%). Antibody titers were significantly higher in patients with an intraventricular vesicle or cyst.

We describe a detection method relying both on the copper displacement from a Sephadex gel by peptides and proteins, and on the subsequent colorimetric determination of the complexed copper. The system described is fully automated and it permits a continuous analysis of column effluents. The choice of cuprizone as a detecting reagent for copper, enables one to bring the detection limit down to 200 ng for albumin and 60 ng for alanylglycylglycin. The specificity of the method is the same as the biuret reaction. Some examples of the possible applications are given.

Refsum's disease although rare is of great interest for it may benefit at least partially from treatment. Its clinical diagnosis depends on the association of pigmented retinitis, polyneuritis and cerebellar syndrome. It is confirmed beyond doubt by the increased C.S.F. protein and phytanemia. A full family history is necessary for it is possible to detect heterozygous carriers of the defect by enzyme studies on fibroblast cultures.

Multiple sclerosis (MS) is often characterized by a intrathecal synthesis of immunoglobulins (Ig) in cerebrospinal fluid (CSF), which may be evaluated in several ways: ratio methods (IgG index, Schuller's or Tourtelotte's formulae) or demonstration of an oligoclonal distribution, or both. In a retrospective study, 256 CSF analyses were evaluated. The 4 parameters studied were disturbed in about the same proportions in each of the 3 MS subgroups of Mac Alpine's classification. An oligoclonal distribution is more rarely present in pathologies other than MS. None of these tests is specific for the diagnosis of MS. Haptoglobin index variations do not distinguish between the different groups of patients. From a physiopathological point of view, however, they may perhaps reveal an acute local inflammatory reaction, different from the immune reaction giving rise to the Ig synthesis.

The oligoclonal gamma-fractions in the cerebrospinal fluid (C.S.F.) from one case of subacute sclerosing panencephalitis (S.S.P.E.) have been studied by means of immunolectrophoresis. The gamma-zone consisted of IgG and free kappa and lambda chains. Besides that, a rabbit immune serum against S.S.P.E. C.S.F. has been prepared. This immune serum did reveal in the gamma-zone one additional protein which is different from IgG and normal tissue proteins. The possibility for this additionnal protein to be of myelinic origin is postulated, because of the demyelinisating nature of the lesion.

The results obtained with gel electrophoresis on CSF samples of multiple sclerosis patients are compared with measurements of CSF IgG indexes (IgG/alb and IgG/total protein). The correlation between these parameters is good, provided the upper normal limit of the IgG/alb index is over 35% and an "overlapping" zone between 21 and 35% is introduced where the IgG/alb index has not the same diagnostic value.