Wallerian degeneration (WD) is the irreversible axonal and myelin damage after the injury to the proximal portion of the axon or its cell body. The most frequent cause of WD in the central nervous ...system is ischemic stroke. Various studies have related the presence of pyramidal tract WD with the severity of motor deficit and partial motor improves. We present a patient with pyramidal tract WD without motor sequelae.
A 55 years old man, hypertense and heavy smoker, suffered a sudden episode of dysarthria and left hemiparesis. Routine analysis showed hypercholesterolemia and an aortic valvular sclerosis on an echocardiogram. Cranial magnetic resonance imaging (MRI) showed multiple supratentorial lacunar infarctions. He was discharged without deficits, antiaggregated with aspirin. Six months later, he suffered a sudden episode of dysarthria. A new cranial MRI disclosed WD of the right pyramidal tract without pyramidal signs on neurologic exam.
Presence of WD on the pyramidal tract is related with pyramidal disability in diverse degree but can develop a complete motor rehabilitation. We present a case of WD of the pyramidal tract without pyramidal deficits that supports the role of supplementary motor areas on motor rehabilitation.
IMPORTANCE: Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for ...neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date. OBJECTIVES: To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions. DATA SOURCES: PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC. STUDY SELECTION: Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex. DATA EXTRACTION AND SYNTHESIS: Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept. MAIN OUTCOME AND MEASURE: The cNfL levels adjusted for age and sex across diagnoses. RESULTS: Data were collected for 10 059 individuals (mean SD age, 59.7 18.8 years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes. CONCLUSIONS AND RELEVANCE: These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
SUMMARY
Cerebrospinal fluid (CSF) from multiple sclerosis (MS) patients contains B cells capable of spontaneous IgG secretion in vitro. This study analyses the function and regulation of these cells. ...CSF cells obtained from nine MS patients actively produced IgG during 2–3 days in culture, and the activity decreased when CSF cells were cultured in serum‐free medium. CSF cells from four controls did not secrete detectable IgG in vitro. Further experiments revealed that IL‐6 played a role on MS CSF IgG‐secreting cells, as can be deduced from the following findings: (i) the addition of exogenous IL‐6, but not of other cytokines, to serum‐free cultures restored missing CSF cell IgG secretion; (ii) the inclusion of anti‐IL‐6, but not of control, blocking MoAb reduced IgG secretion by CSF cells in fetal calf serum (FCS)‐containing cultures; and (iii) CSF cells were capable of active IL‐6 production in the presence of FCS. These results suggest that endogenous IL‐6 production by MS CSF cells seems to be responsible for inducing CSF IgG‐secreting B cells to reach terminal differentiation.
We studied the presence of serum antiphospholipid antibodies (APA) in 35 patients with migraine and 75 controls. None of the controls showed APA, while we found these antibodies in five patients out ...of the 35 studied (p = 0.003). The clinical features of migraineurs with APA were similar to those of patients without them. After a follow-up of one to two years, no patient suffered any neurological complications or developed any clinical features that would suggest the presence of autoimmune disease. Our results suggest that APA are not prominent in the pathogenesis of migraine attacks, or significant in the course of otherwise healthy migraine patients.
SUMMARY
HLA class I antigens are thought to be integral membrane proteins. However, soluble forms of these molecules have been detected. Our laboratory has recently shown that the predominant form of ...these soluble proteins present in human serum, spleen tissue and culture supernatant of activated lymphocytes exhibits molecular weight and structure similar to classical HLA class I antigens, but lacks HLA A or B polymorphic determinants. In the present study, the secretion of such soluble proteins by lymphocytes has been further explored. Phytohaemagglutinin‐stimulated normal lymphocytes secrete considerable quantities of soluble HLA (sHLA) class I proteins. This secretion seems to be a general property of lymphocytes, since activation of T as well as B cells by appropriate mitogens equally induce sHLA I secretion. Lymphocytes require RNA and protein synthesis, but not DNA synthesis, for the secretion to occur. Kinetic studies reveal that maximal sHLA I secretion precedes the peak of DNA synthesis by 24 h. In vitro stimulation with antigens or alloantigens also provokes sHLA I secretion. Moreover, this phenomenon has also been detected for in n'ro‐aclivated lymphocytes, as enhanced spontaneous sHLA I secretion was observed in cultures of Low‐density blastic B and T cells, and of blood lymphocytes obtained from normal subjects who had received a booster immunization 5 days earlier. Interferon‐gamma (IFN‐γ) increases the expression of membrane‐bound class I antigens but does not induce any sHLA I secretion, suggesting that both molecules are under different regulatory mechanisms. Our results indicate that human lymphocytes, upon stimulation, actively secrete considerable amounts of a soluble form of these biologically relevant proteins.
Patients with migraine have a platelet hyperaggregability. As this alteration could be the consequence of an abnormal lipid composition of platelet membranes, we studied the phospholipid specimens ...and the cholesterol/phospholipid ratio in platelet of neuron patients suffering from migraine. The cholesterol/phospholipid ratio was 0.7 +/- 0.1 (normal 0.6 +/- 0.1, molar ratio). The proportion of five main platelet phospholipids components including phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, phosphatidylserine, and phosphatidylinositol, were also normal. These data suggest that platelet hyperactivity in patients with migraine is not due to an altered lipid content of those cells.
We have studied the intrathecal synthesis of soluble class I antigens (sHLA), reflected by the index IH = (CSF sHLA/serum sHLA)/(CSF albumin/serum albumin), in multiple sclerosis (MS). IH was ...increased in patients in relapse, but normal in patients in remission; these findings show that there is a high lymphocyte activation within the central nervous system in patients with clinically active MS.
Lithium-induced headache Alvarez-Cermeño, J C; Fernández, J M; O'Neill, A ...
Headache,
April 1989, Letnik:
29, Številka:
4
Journal Article
Recenzirano
A 23-year old woman developed headache and papilledema due to benign intracranial hypertension (BIH) while taking lithium carbonate for only seven months because of manic-depressive disease. Having ...discarded other causes, drug ingestion was the most likely etiology of the syndrome since it was observed that symptoms improved upon lithium withdrawal and worsened when the treatment was restarted. This report shows that BIH may appear as a side-effect of relatively short-term therapy with lithium and, therefore, funduscopic exams should be performed in every patient receiving this drug.
sHLA are secreted by B and T lymphocytes upon activation. These antigens are present in serum and cerebrospinal fluid (CSF). The establishment of a sHLA index, IH = (CSF sHLA/serum sHLA)/(CSF ...albumin/serum albumin) helped us to define that values above 9.7 reflect an intrathecal synthesis of these proteins. IH was significantly increased in a group of patients with intrathecal production of IgG against HIV-1 (HIV) and directly correlated with the synthesis of such antibodies. Therefore, IH seems to be an index of lymphocyte activation in CNS.
Recent reports have shown association between CYP2D6 polymorphism and neuronal degenerative diseases such as Parkinson's disease. We investigated the association between this polymorphism and the ...risk for developing multiple sclerosis (MS). Leucocyte DNA from 118 MS patients and a control group of 200 unrelated healthy individuals was studied for the occurrence of 8 different CYP2D6 allelic variants by using allele-specific PCR amplification, XbaI and EcoRI RFLP analyses. The frequencies for these allelic variants in the MS and control groups were, respectively: CYP2D6wt 75.0% and 79.3%, CYP2D6A 0.4% and 1.3%, CYP2D6B 11.4% and 12.0%, CYP2D6C 4.2% and 2.0%, CYP2D6D 3.0% and 2.3%, CYP2D6L 0.8% and 0.3%, CYP2D6L2 5.1% and 3.0%. The frequencies of subjects with high CYP2D6 activity (those carrying two or more functional genes) were 77.1% and 73.5% in MS and control groups. The frequencies of subjects with absent CYP2D6 activity (those lacking functional genes) were 3.4% and 4.5% in MS and control groups, respectively. These results indicate that mutations at the CYP2D6 gene do not seem to be a factor in determining susceptibility to MS.
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