Chronic active VZV infection manifesting as zoster sine herpete,zoster paresis and myelopathy

After lumbar-distribution zoster, an HTLV-1-seropositive woman developed chronic radicular sacral-distribution pain (zoster sine herpete), cervical-distribution zoster paresis and thoracic-distribution myelopathy. Detection of anti-varicella zoster virus (VZV) IgM and VZV IgG antibody in cerebrospinal fluid (CSF), with reduced serum/CSF ratios of anti-VZV IgG compared to normal serum/CSF ratios for albumin and total IgG, proved that VZV caused the protracted neurological complications. Diagnosis by antibody testing led to aggressive antiviral treatment and a favorable outcome.     

Acute, chronic, and recurrent varicella zoster virus neuropathy without zoster rash

The authors report three patients with acute, chronic, and recurrent neuropathy associated with varicella zoster virus (VZV) infection but without zoster rash. CSF of all three patients contained VZV immunoglobulin G antibody, but not herpes simplex virus. In two patients, serum/CSF ratios of VZV immunoglobulin G were reduced compared to normal ratios for immunoglobulin G and albumin, and one patient also had VZV immunoglobulin M in CSF. All three patients received antiviral therapy and improved. The diagnosis of nervous system infection by VZV may be confirmed by the presence of antibody to VZV in CSF even without detectable VZV DNA.     

Increased levels of inflammatory chemokines in amyotrophic lateral sclerosis

Background and purpose:  Amyotrophic lateral sclerosis (ALS) is classically assumed to be a neurodegenerative disorder. Inflammation has been observed in CNS tissue in ALS patients. We investigated the expression and prognostic relevance of proinflammatory chemokines in ALS.
Methods:  We analyzed nine chemokines, eotaxin, eotaxin-3, IL-8, IP-10, MCP-1, MCP-4, macrophage derived chemokine (MDC), macrophage inflammatory protein-1β (MIP-1β), and serum thymus and activation- regulated chemokine (TARC) in serum and cerebrospinal fluid (CSF) of 20 ALS- and 20 non-inflammatory neurological disease (NIND)-patients.
Results:  MCP-1 and IL-8 levels in CSF in ALS were significantly higher than in NIND (1304 pg/ml vs. 1055 pg/ml, P  = 0.013 and 22.7 pg/ml vs. 18.6 pg/ml, P  = 0.035). The expression of MCP-1 and IL-8 were higher in CSF than in serum ( P  < 0.001). There was a trend towards higher MCP-1 CSF levels in ALS patients with shorter time between first symptoms and diagnosis ( r  = −0.407; P  = 0.075).
Conclusions:  We confirmed previous findings of increased MCP-1 levels in CSF of ALS patients. Furthermore, increased levels of IL-8 in CSF suggest a stimulation of a proinflammatory cytokine cascade after microglia activation. We found a tendency for higher MCP-1 values in patients with a shorter diagnostic delay, who are known to have also a shorter survival. This may suggest an association of higher MCP-1 levels with rapidly progressing disease.     

IL-10 levels in cerebrospinal fluid and serum of patients with severe traumatic brain injury: relationship to IL-6, TNF-alpha, TGF-beta1 and blood-brain barrier function

Controlling the extent of inflammatory responses following brain injury may be beneficial since posttraumatic intracranial inflammation has been associated with adverse outcome. In order to elucidate the potential role of anti-inflammatory mediators, the production of interleukin-10 (IL-10) was monitored in paired cerebrospinal fluid (CSF) and serum of 28 patients with severe traumatic brain injury (TBI) and compared to control samples. The pattern of IL-10 was analyzed with respect to the patterns of IL-6, tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) in both fluids during a time period of up to 22 days. In parallel, the function/dysfunction of the blood-brain barrier (BBB) was monitored using the CSF-/serum-albumin quotient (Q(A)) and compared to intrathecal cytokine levels. Mean IL-10 concentration in CSF was elevated in 26 out of 28 TBI patients (range: 1.3-41.7 pg/ml) compared to controls (cut-off: 1.06 pg/ml), whereas only seven patients had elevated mean IL-10 concentration in serum (range: 5.4-23 pg/ml; cut-off: 5.14 pg/ml). The time course of IL-10 was similar in both fluids, showing a peak during the first days and a second, lower rise in the second week. Intrathecal IL-10 synthesis is hypothesized since CSF-IL-10 levels exceeded serum-IL-10 levels in most of the patients, IL-10-index (CSF/serum-IL-10/QA) was elevated in 23 individuals, and elevation of CSF-IL-10 showed to be independent from severe BBB dysfunction. Neither CSF nor serum IL-10 values correlated with the dysfunction of the BBB. IL-10, IL-6 and TGF-beta1 showed similar patterns in CSF over time, whereas rises of TNF-alpha corresponded to declines of IL-10 levels. Our results suggest that IL-10 is predominantly induced intrathecally after severe TBI where it may downregulate inflammatory events following traumatic brain damage.     

Cerebrospinal fluid interleukin-6 levels in patients with West syndrome

Elevated cytokine response has been reported in patients with epileptic seizures. The objective of this study was to investigate the possible role of interleukin-6 (IL-6) in the pathogenesis of infantile spasms in West syndrome (WS). We measured IL-6 levels in cerebrospinal fluid (CSF) obtained from the newly diagnosed patients with WS. Twelve patients with WS (Group I) were classified as symptomatic WS (Group IA) in eight and as cryptogenic WS (Group IB) in four. The results were compared with control groups including patients with tonic-clonic seizures associated with two different kind of inflammation of central nervous system; Group IIA (infection): bacterial meningitis/encephalitis and Group IIB (trauma): post-traumatic seizures. There was no statistically significant difference between the mean values of CSF IL-6 levels in patients with WS (2.95 +/- 2.31 pg/ml) and those of subgroups of WS (Group IA: 2.26 +/- 2.01 pg/ml and Group IB: 4.33 +/- 2.52 pg/ml). Both control groups had highly increased IL-6 levels in CSF (Group IIA: 193.05 +/- 185.52 pg/ml and Group IIB: 112.74 +/- 167.44 pg/ml) than those of the patients with WS. Elevated IL-6 response in patients with tonic-clonic seizures associated with inflammation of central nervous system might be due to the seizures themselves or related to the underling etiology (infection or trauma). However, no elevated IL-6 response was found in patients with infantile spasms.     

Interleukin 1beta and interleukin 6 relationship with paediatric head trauma severity and outcome.

BACKGROUND: Based on the known inflammatory role of interleukins (IL), we evaluated IL-1beta and IL-6 expressions and their association with the severity of traumatic brain injury (TBI; Glasgow Coma Scale [GCS]) and the outcome (Glasgow Outcome Score [GOS]) recorded in a paediatric population. DESIGN: The design was a perspective observational clinical study carried out in the paediatric intensive care unit of the University Hospital. METHODS: We measured the IL-1beta and IL-6 levels in 14 children with severe TBI (patients) and in 12 children with obstructive hydrocephalus (control group). Cerebrospinal fluid (CSF) and plasma samples were collected 2 h (T1) and 24 h (T2) after TBI. Interleukins were assayed using the immunoenzymatic method. RESULTS: The IL-1beta mean level was significantly lower than the IL-6 mean level both in the CSF and plasma of TBI children. In the CSF, the IL-1beta level increased from 55.71+/-72.79 pg/ml at T1 to 106.10+/-142.12 pg/ml at T2 and the IL-6 level increased from 405.43+/-280.28 pg/ml at T1 to 631.57+/-385.35 pg/ml at T2; a similar trend was observed in plasma. We found a statistically significant correlation between the increase in CSF and plasma interleukin levels between T1 and T2 and head injury severity (GCS相似文献   

Chemokines CXCL10 and CXCL11 in the cerebrospinal fluid of patients with tick-borne encephalitis

OBJECTIVES: The aim of our study was to determine whether cerebrospinal fluid (CSF) of patients with tick-borne encephalitis (TBE) contains CXCL10, CXCL11, p40 subunit of interleukin-12 (IL-12)/IL-23, IL-18 and IL-15. We compared serum and CSF concentrations of CXCL10 and analysed the possible concentration gradient of this chemokine between the periphery and central nervous system. MATERIALS AND METHODS: The study enrolled 19 TBE patients and 10 patients with non-inflammatory neurological diseases. RESULTS: CSF of TBE patients contained CXCL10 (median 217 pg/ml), CXCL11 (8.3 pg/ml), p40 subunit of IL-12/IL-23 (38.9 pg/ml), IL-18 (30.1 pg/ml) and IL-15 (5.9 pg/ml). CXCL10 in the CSF of TBE patients was higher compared with serum (median 62 pg/ml, P < 0.001). CONCLUSION: CSF of TBE patients contains CXCL10, CXCL11, p40 subunit of IL-12/IL-23, IL-18 and IL-15. Increased CXCL10 concentration in CSF suggests a role for this chemokine in the recruitment of CXCR3-expressing T-cells into the CSF of TBE patients.     

Interleukin-1β is increased in the cerebrospinal fluid of patients with small infarcts

Background and purpose:  Interleukin-1beta (IL-1β) and interleukin-6 (IL-6) are involved in inflammatory responses during large vessel occlusion in animal models. The aim of this study was to investigate the intrathecal levels of cytokines in patients with acute small infarcts.
Methods:  Forty patients with acute minor stroke and 32 non-stroke patients (including 29 age- and gender-matched subjects) who received operations with spinal anesthesia were studied prospectively and underwent measurements of cerebrospinal fluid (CSF) IL-1β and IL-6 levels.
Results:  After an age- and gender-matched analysis of 58 patients (29 pairs), the mean intrathecal levels of IL-1β were 0.80 pg/ml in patients with small infarcts and 0.59 pg/ml in non-stroke patients ( P  <   0.0001). In addition, the mean CSF levels of IL-6 were 21.54 pg/ml and 7.52 pg/ml in the stroke and control groups, respectively ( P  =   0.38). These results were consistent with the data without matching. The CSF levels of IL-1β in the 40 stroke patients were significantly higher than in the 32 non-stroke controls ( P  <   0.0001).
Conclusions:  The proinflammatory cytokine IL-1β, but not IL-6, remained elevated in the CSF of patients in the acute stage of small infarcts.     

The protean manifestations of varicella-zoster virus vasculopathy

Varicella-zoster virus (VZV) vasculopathy in the central nervous system (CNS) affects large and small cerebral vessels. Large-vessel disease is most common in immunocompetent individuals, whereas small-vessel disease usually develops in immunocompromised patients. In some patients, both large and small vessels are involved. Neurological features are protean. Neurological disease often occurs months after zoster and sometimes without any history of zoster rash. Magnetic resonance imaging (MRI) scanning, cerebral angiography, and examination of cerebrospinal fluid (CSF) with virological analysis are needed to confirm the diagnosis. VZV vasculopathy patients do not always have VZV DNA in CSF, but diagnosis can be confirmed by finding anti-VZV antibody in CSF, along with reduced serum/CSF ratios of VZV immunoglobulin G (IgG) compared to albumin or total IgG. When VZV vasculopathy develops months after zoster, antiviral treatment is often effective.     

Predictive value of serum interleukin-6 level in influenza virus-associated encephalopathy

OBJECTIVE: In Japan, >200 children with influenza virus-associated encephalopathy were reported in 1999 and the mortality rate was high. The levels of tumor necrosis factor-alpha (TNFalpha) and interleukin-6 (IL-6) in both CSF and serum were significantly increased in severe cases. The authors found a correlation between elevated serum cytokine levels and mortality and neurologic morbidity. METHODS: TNFalpha, IL-6, soluble tumor necrosis factor receptor 1 (sTNF-R1), interferon-gamma (IFNgamma), and IL-2 were measured by the ELISA method in sera from six children with encephalopathy before and during therapy, and in six age-matched controls with influenza type A virus infection. RESULTS: The increases in the serum TNFalpha, IL-6, and sTNF-R1 levels were statistically significant at the onset of symptoms before therapy, but the IL-6 level was most useful for diagnosis. The serum IL-6 levels were >6,000 pg/mL in children with brain stem dysfunction, about 150 pg/mL in children without brain stem dysfunction, and <80 pg/mL in controls. The time course of the serum IL-6 level also reflected the clinical condition. Once the serum IL-6 level was increased to >15,000 pg/mL, none of the children survived. The lower the maximal serum IL-6 level, the milder the CNS sequelae. CONCLUSION: The serum IL-6 level may be the most useful indicator for the diagnosis and the clinical severity of influenza virus-associated encephalopathy.     

Decreased levels of interleukin-10 and transforming growth factor-beta 2 in cerebrospinal fluid of patients with high grade astrocytoma

OBJECTIVE: Glioma cells can produce anti-inflammatory cytokines such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) which inhibit T cell and monocyte function. It is unknown if production of these cytokines is limited to the site of tumor or these molecules are also released to cerebrospinal fluid and blood. The goal of our study was to determine if patients with astrocytoma have increased levels of IL-10 and TGF-beta 2 in cerebrospinal fluid (CSF) and serum. METHODS: CSF and serum samples were taken from 16 patients with astrocytoma of grade III or grade IV according to the WHO classification and from 28 age- and gender-matched controls (patients with normal pressure hydrocephalus or with lumbar disk herniation). Cytokine concentrations were measured using ELISA methods. RESULTS AND DISCUSSION: There was no difference in serum levels of IL-10 and TGF-beta 2 between groups. Patients with astrocytoma had decreased levels of IL-10 (0.9 +/- 1.2 versus 3.5 +/- 9.2 pg/ml, p=0.01) and TGF-beta 2 (0.0 +/- 0.0 versus 5.4 +/- 9.4 pg/ml, p=0.05) in CSF compared to controls. Because serum IL-10 and TGF-beta 2 levels are similar in patients with astrocytoma and in controls, these cytokines are probably not directly involved in peripheral monocyte and T cell deactivation.     

Serum and CSF levels of MCP-1 and IP-10 in multiple sclerosis patients with acute and stable disease and undergoing immunomodulatory therapies

The two chemokines, monocyte chemoattractant protein (MCP)-1 and gamma-interferon inducible protein (IP)-10, are thought to be involved in the pathogenesis of multiple sclerosis (MS). We measured MCP-1 and IP-10 levels in serum and CSF samples from 38 acute and 25 stable MS patients and from 40 controls. The latter consisted in patients with other inflammatory neurological diseases (OIND) or with non-inflammatory neurological diseases, and healthy controls. CSF MCP-1 levels exceeded those found in serum in all the patients studied as well as in healthy controls. CSF MCP-1 levels were significantly lower in acute MS [468+/-(S.E.M.) 18 pg/ml] than in stable MS (857+/-104 pg/ml). When detectable, serum and CSF IP-10 levels were significantly higher in acute MS (serum 331+/-66 pg/ml; CSF 118+/-16 pg/ml) than in stable MS (serum 69+/-7 pg/ml; CSF 25+/-2 pg/ml). Among OIND patients, those with HIV-1-associated dementia showed high serum and CSF levels of both MCP-1 and IP-10. Those with encephalitis showed high serum and CSF levels of IP-10 and CSF mononuclear pleiocytosis. We also evaluated the effects of 6-methylprednisolone or IFN-beta1a therapy on circulating MCP-1 and IP-10 levels. Neither MCP-1 nor IP-10 post-therapy levels varied significantly from baseline values. Our findings suggest that (a) MCP-1 could be constitutively produced within the brain; (b) MCP-1 and IP-10 CSF levels in acute MS vary significantly from those in stable MS, and these variations are inverse; and (c) current MS therapies do not modify circulating levels of MCP-1 and IP-10.     

Soluble interleukin-1 receptor type II levels are elevated in cerebrospinal fluid in Alzheimer's disease patients

Evidence from epidemiological, clinical and experimental studies favour the hypothesis that inflammatory events are part of the neuropathology in Alzheimer's disease. Proinflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) have been found in activated microglia in the vicinity of amyloid plaques in Alzheimer's disease brain. In the present study, the levels of soluble IL-1 receptor type II (sIL-1R type II), IL-1 receptor antagonist (IL-1ra), IL-1beta, IL-6 and TNF-alpha were analyzed in cerebrospinal fluid (CSF) samples from Alzheimer's disease patients and control subjects. The levels of sIL-1R type II were significantly higher in CSF from Alzheimer's disease patients than in CSF samples from control subjects (38.5+/-8 pg/ml (mean+/-S.E.M.) vs. 7.9+/-4 pg/ml, p<0.05). Measurements of the proinflammatory cytokines IL-6 and TNF-alpha showed no significant difference between the two groups, and the levels of IL-1beta and IL-1ra in the present material were too low to permit detection. The increased levels of sIL-1R type II may reflect a compensatory mechanism to balance an increased release of IL-1 receptor agonists in the Alzheimer's disease brain.     

Cerebrospinal fluid levels of interleukin-6 and interleukin-12 in children with meningitis

Purpose  Certain cytokines play important roles in the pathophysiology of meningitis. The main purpose of this study was to investigate if the levels of interleukin-6 (IL-6) and interleukin-12 (IL-12) in cerebrospinal fluid (CSF) could be diagnostic predictors of bacterial meningitis in children. Methods  CSF was obtained from 95 patients suspected with meningitis. These cases were classified to the bacterial meningitis (n = 12), aseptic meningitis (n = 41), and nonmeningitis (n = 42) groups. The levels of IL-6 and IL-12 in CSF were measured using the enzyme-linked immmunosorbent assays test. Results  The CSF IL-6 levels in the bacterial meningitis group (45.2 ± 50.0 pg/ml) were significantly higher than those in the aseptic meningitis group (12.9 ± 10.2 pg/ml) and the nonmeningitis group (6.5 ± 7.8 pg/ml; p < 0.05). The CSF IL-12 levels in the bacterial meningitis group (69.8 ± 67.1 pg/ml) were significantly higher than those in the aseptic meningitis group (22.9 ± 10.8 pg/ml) and the nonmeningitis group (15.3 ± 11.2 pg/ml; p < 0.05). With regard to diagnosis, the measurement of CSF IL-6 and IL-12 levels showed sensitivities of 96% and 96%, respectively, and specificities of 51% and 75%, respectively. Conclusion  It is suggested that the CSF IL-6 and IL-12 levels are useful markers for distinguishing bacterial meningitis from aseptic meningitis.     

Subclinical reactivation of varicella zoster virus in all stages of HIV infection

Analysis of 200 paired serum and cerebrospinal fluid (CSF) samples from 180 HIV-positive individuals, 136 of whom had AIDS, revealed intrathecal synthesis of antibodies specific for varicella zoster virus (VZV) in 28 (16%) individuals, measles virus in 15 (8%), herpes simplex virus-1 (HSV-1) in 1 (0.6%), and HSV-2 in none. Of the 28 subjects with a positive VZV antibody specificity index, only 1 had zoster rash at the time of serum and CSF sampling; of the total 180 HIV-positive subjects, 146 (81%) had no history of zoster. Based on an estimated 33.4 million HIV-positive individuals worldwide, subclinical reactivation of VZV in even less than 16% of HIV-positive people suggests the possibility that millions of people have active VZV infection of the central nervous system. In cases of VZV vasculopathy, myelopathy and even zoster sine herpete, the CSF is often positive for anti-VZV antibody, but negative for VZV DNA. To rule out VZV infection of the nervous system, CSF must be tested for VZV DNA and anti-VZV IgG and IgM antibody.     

Vitamin B12 levels in serum and cerebrospinal fluid of people with Alzheimer's disease

Vitamin B12 levels in the serum and the cerebrospinal fluid (CSF) were compared between patients with Alzheimer's disease (AD) and senile dementia of Alzheimer's type (SDAT) (AD group) and patients with multi-infarct dementia (MID group). The B12 levels in the serum and the CSF were 742 +/- 359 pg/ml and 28 +/- 7 pg/ml (mean +/- SD), respectively, in the AD group, and 962 +/- 254 pg/ml and 50 +/- 26 pg/ml, respectively, in the MID group. CSF B12 levels were significantly lower in the AD group than in the MID group, whereas the serum levels were not different. At the same time, the serum levels of almost all patients were within the normal range, whereas the CSF levels were 25 pg/ml or lower in 10 of 12 AD patients. Therefore, this low level in the CSF is considered to be a characteristic finding in the AD group.     

Intracerebroventricular injection of interleukin-1 stimulates the release of high levels of interleukin-6 and interleukin-1 receptor antagonist into peripheral blood in the primate.

Previous studies in the rodent have shown that the cytokine IL-1 can act within the brain to influence peripheral IL-6 secretion. In order to determine if such an interaction occurs in the primate, we have compared the effects of intracerebroventricular vs. intravenous injection of IL-1beta on the release of IL-6 into the peripheral circulation of the monkey. The effects of i.c.v. IL-1beta on the release of the IL-1 receptor antagonist (IL-1ra) were studied in parallel. For comparison, we have also measured the release of both IL-6 and IL-1ra into lumbar CSF after i.c.v. IL-1beta injection. Ten ovariectomized rhesus monkeys with indwelling lateral ventricular and peripheral venous cannulae were studied. Human rIL-1beta (400 ng) was infused either i.c.v. or i.v. over 30 min and blood samples were collected for IL-6 and IL-1ra measurement by monoclonal human ELISAs. Although both i.c.v. and i.v. IL-1beta stimulated IL-6 and IL-1ra release into peripheral blood, the stimulation was much more profound after i.c.v. injection (p < 0.001). Peak IL-6 levels were 2010 +/- 590 pg/ml after i.c.v. IL-1beta compared to 243 +/- 60 pg/ml after i.v. IL-1beta. Peak IL-1ra levels were 61,310 +/- 16,190 pg/ml after i.c.v. IL-1beta compared to 18,175 +/- 4270 pg/ml after i.v. IL-1beta. There was no significant effect of an i.c.v. saline infusion on peripheral IL-6 or IL-1ra levels. In four animals, lumbar CSF was collected 7 h after i.c.v. IL-1beta injection. The mean concentration of IL-6 in CSF was 103, 570 +/- 13,780 pg/ml after i.c.v. IL-1beta vs. 224 +/- 190 pg/ml after i.c.v. saline injection; IL-1ra was 47,460 +/- 6290 pg/ml vs. 1040 +/- 550 pg/ml. As expected, both i.c.v. and i.v. IL-beta stimulated ACTH and cortisol release; the stimulation was significantly greater after i.c.v. compared to i.v. administration (p < 0.001). Thus, in the monkey, i.c.v. injection of IL-1beta stimulates the release of large amounts of IL-6 and IL-1ra into the CSF and the peripheral circulation. Both IL-6 and IL-1ra were released into the peripheral circulation to a much greater extent after i.c.v. compared to i.v. IL-1beta infusion. These studies provide further support in the primate for a mechanism by which inflammation within the brain could induce a variety of systemic responses.     

The soluble 60-kDa tumour necrosis factor receptor: no difference found between patients with relapsing-remitting multiple sclerosis and controls: increasing levels are associated with the recovery from Guillain-Barré syndrome

We determined serum and cerebrospinal fluid (CSF) levels of the soluble 60-kDa tumour necrosis factor (TNF) receptor (sTNF-R p60) in 50 patients with relapsing-remitting multiple sclerosis (MS) and in 18 patients with Guillain-Barré syndrome (GBS). Neither in serum nor in CSF samples was there a statistically significant difference between mean receptor concentrations of patients with MS (serum: 1064, SD 262 pg/ml; CSF: 555, SD 130 pg/ml), with other noninflammatory neurological diseases (serum: 1008, SD 248 pg/ml; CSF: 530, SD 112 pg/ml) and with healthy control subjects (serum: 918, SD 180 pg/ml). In order to determine disease activity, magnetic resonance imaging (MRI) of the brain was performed in all MS patients. The mean sTNF-R p60 levels of patients who showed gadolinium DTPA enhancement on MRI were not different from those without enhancement (1034, SD 274 pg/ml vs 1099, SD 248 pg/ml in serum samples and 546, SD 109 pg/ml vs 565, SD 152 pg/ml in CSF samples). In GBS, the sTNF-R p60 levels of serum and CSF samples were significantly higher than in MS and all control groups except for the group with viral meningitis (VM) (GBS: 1544, SD 834 pg/ml in serum, 882, SD 147 pg/ml in CSF; VM: 1518, SD 375 pg/ml in serum, 1131, SD 611 pg/ml in CSF; P < 0.001 for serum samples and P < 0.005 for CSF samples). Serial serum sTNF-R p60 measurements in 13 patients with GBS showed an increase in receptor levels parallel with the recovery from the disease (1276, SD 374 pg/ml at the time of disease onset, 1554, SD 482 pg/ml 14–24 days later and 1787, SD 525 pg/ml after 28–32 days). From our results and the conflicting data of previous studies, we could not agree with the suggestion that the assessment of sTNF-R p60 in MS patients is a useful marker for disease activity. In GBS, subsequently increasing sTNF-R p60 levels are associated with recovery from the disease. It remains to be shown whether they might represent a relevant pathogenetic factor during this stage of GBS. Received: 31 October 1997 Received in revised form: 26 January 1998 Accepted: 10 February 1998     

Experimental axonal injury triggers interleukin-6 mRNA, protein synthesis and release into cerebrospinal fluid.

Diffuse axonal injury is a frequent pathologic sequel of head trauma, which, despite its devastating consequences for the patients, remains to be fully elucidated. Here we studied the release of interleukin-6 (IL-6) into CSF and serum, as well as the expression of IL-6 messenger ribonucleic acid (mRNA) and protein in a weight drop model of axonal injury in the rat. The IL-6 activity was elevated in CSF within 1 hour and peaked between 2 and 4 hours, reaching maximal values of 82,108 pg/mL, and returned to control values after 24 hours. In serum, the levels of IL-6 remained below increased CSF levels and did not exceed 393 pg/mL. In situ hybridization demonstrated augmented IL-6 mRNA expression in several regions including cortical pyramidal cells, neurons in thalamic nuclei, and macrophages in the basal subarachnoid spaces. A weak constitutive expression of IL-6 protein was shown by immunohistochemical study in control brain. After injury, IL-6 increased at 1 hour and remained elevated through the first 24 hours, returning to normal afterward. Most cells producing IL-6 were cortical, thalamic, and hippocampal neurons as confirmed by staining for the neuronal marker NeuN. These results extend our previous studies showing IL-6 production in the cerebrospinal fluid of patients with severe head trauma and demonstrate that neurons are the main source of IL-6 after experimental axonal injury.     

Varicella zoster virus meningoencephalitis accompanied by rhabdomyolysis without skin eruption

We report a case of a 38-year-old man with a Varicella zoster virus (VZV) reactivation who manifested meningoencephalitis accompanied by rhabdomyolysis without a skin eruption. During the acute phase, VZV DNA was detected in serum and cerebrospinal fluid (CSF) by the polymerase chain reaction (PCR). After 16 days, all symptoms and signs resolved, and follow-up PCR studies revealed negative conversion of VZV in the serum and CSF. We discuss the possible underlying mechanism of VZV reactivation in our patient. This is the first case report of VZV reactivation meningoencephalitis accompanied by rhabdomyolysis without skin eruption demonstrated by viral DNA in the serum and CSF.