Neuropathological brain studies of patients with anti- Hu encephalitis revealed severe loss of neurons in combination with inflammatory infiltrates with predom- inantly T lymphocytes . These inflammatory signs and neurodegeneration suggest that early efficient treat- ment might be beneficial for the clinical outcome. We hypothesize that the treatment benefit might be of par- ticular success in patients with isolated peripheral neur- opathy prior to additional encephalitis. Analysis of the CSF with determination of intrathecalsynthesis of anti- Hu antibodies presents a useful tool to discriminate between these both groups of patients with and without involvement of the CNS. Our findings might be thus relevant for the treatment of these patients.
Although the number of patients affected with the disease is low, this zoonosis is important in our environment. In our sample, we studied patients affected between 2002 and 2007, the diagnosis being by the presence of eosi- nophils in CSF and clinical symptoms such as fever, vom- iting and headache. In Cuba there is no other parasite that can cause eosinophilia in the CSF. Infection with A. canto- nensis produces a prominent intrathecal production of IgM, IgA and IgG seven to ten days after the beginning of symptoms as we have reported earlier . In this study using the first diagnostic lumbar puncture, IgE intrathecalsynthesis was demonstrated but not IgM, IgA or IgG syn- thesis.
It has been postulated that MS is an autoimmune disease, and considerable efforts have been made to find a particular antigen associated with its physiopathology (1–4). The presence of T cells, macrophages, and antibodies in MS demyelinating plaques has been established (5). It has been postulated that T cells and macrophages play an important role in the inflammatory response observed in MS and that antibodies and complement participate in initial plaque development (6, 7). Increasing evidence indicates that IgM antibodies are also involved in this process. In this dis- ease, local CNS (intrathecal) synthesis of IgM, but not of IgG or IgA, correlates with intrathecalsynthesis of complement compo- nent C3 (8) and with the cerebrospinal fluid (CSF) concentration of myelin basic protein, an index of demyelination (9).
Reiber et al. ; IgG index ; and finally, the pres- ence of oligoclonal bands (OCBs) in CSF and in serum. Concentrations of CSF and serum proteins were measured nephelometrically (ProSpect System, Dade Behring, Sie- mens, Germany) according to the manufacturer’s instruc- tions. For detection of OCBs, CSF and serum samples were diluted to IgG concentrations of 20 mg/l followed by isoelectric focusing (IEF; Hydragel 9 CSF Isofocusing, Sebia, France) and immunofixation. Intrathecal Ig synthe- sis was considered significant if IF-values exceeded 10 % in the quantitative analysis. An elevated IgG index was de- fined as ≥ 0.65 and/or an increase of > 30 % compared to values of an earlier LP. The term “spurious quantitative intrathecalsynthesis” is used in the context of this study if elevated intrathecal immunoglobulin fractions or an in- creased IgG index were caused by the non-steady-state condition between serum and CSF occurring shortly after therapeutic apheresis.
under study with a range of values of Q albumin (QAlb) is shown in figure 1. The Q C 4 values for all twelve patients with meningoencephalitis are above the lower thin hyper- bolic line. For nine of these twelve patients Q C 4 was located above the upper solid line showing that these patients synthesized C 4 intrathecally. The Q C 4 for all con- trol patients is in the area between the thick hyperbolic line and the lower thin line, indicating that there is no CNS synthesis of this component. Also included is the QIgA of the patients with inflammatory meningoen- cephalitis and only five of these are in the region that indi- cates intrathecalsynthesis. Another two patients had no detectable IgA in CSF. Hence the pattern of intrathecalsynthesis of IgA is not the same as for C 4 , suggesting that IgA has a different role in the immune response, despite
determined nephelometrically (BN ProSpec, Dade Behr- ing, Germany). Intrathecalsynthesis of IgG to HSV, VZV, CMV, MV, RV, and Bb was determined by calculat- ing the respective antibody indices (AI): AI=QIgG[spec]/ QIgG[total], if QIgG[total]<Qlim, and AI=QIgG[spec]/ Qlim, if QIgG[total]>Qlim, with QIgG[spec]=IgGspec [CSF]/IgGspec[serum], and QIgG[total]=IgGtotal[CSF]/ IgGtotal[serum][1,3]. The upper reference range of QIgG[total], Qlim, was calculated according to Reiber’s formula . No lumbar puncture or phlebotomy was performed for this study, and no stored CSF or serum samples were used for this study. Instead, all data were retrieved retrospectively by an automated database search and analyzed anonymously. As clinical data were not available from all patients due to anonymization, a very conservative cut-off for AI positivity (2.0 instead of
sis of borrelial IgM and IgG antibodies was detected in 17/34 (50.0%) and 16/34 (47.0%) patients, respectively, with clini- cally evident Lyme neuroborreliosis, in 0/26 and 2/26 (7.7%) patients with suspected Lyme neuroborreliosis, and in 4/32 (12.5%) and 3/32 (9.4%) patients with TBE (Table 3). Al- though calculations of intrathecal antibody production on the basis of serum and CSF antibodies determined using the Liai- son test gave positive results more often than the correspond- ing findings from the IDEIA kit, a statistically significant dif- ference between the two tests was found only for intrathecalsynthesis of IgM antibodies in patients with clinically evident Lyme neuroborreliosis (17/34 versus 11/34; P ⫽ 0.0315).
pathology . The origin of long-term secreting PCs, likely the source of intrathecally synthesized IgG, has not been established yet. Moreover, the progressive colonization of MS meninges by FLS suggests that local B cell maturation to PCs may support the intrathecalsynthesis of IgM and IgG . However, since FLS accumulation seems to parallel disease progression (i.e., they were demonstrated in high percentage in progressive MS cases, rarely in RRMS and not at clinical onset), we would expect to observe qualita- tive modifications of the IgGOB patterns over the course of the disease. On the contrary, longitudinal studies demon- strated that IgGOB are almost qualitatively stable [15–19].
Detection of intrathecal immunoglobulin M (IgM) synthesis is a specific and sensitive parameter for the detection of CNS involvement in cases of HAT caused by T. brucei gambiense (1), but the technology used to assess intrathecalsynthesis is not suitable for use in the field. As a consequence of intrathecalsynthesis, the levels of IgM and trypanosome-specific antibod- ies are increased in the CSF of patients with the meningoen- cephalitic stage (7, 13). Two point-of-care tests were developed on this basis: the LATEX/IgM assay, for the detection of IgM in the CSF of patients with sleeping sickness (10), and the LATEX/T. brucei gambiense assay, for the detection of try- panosome-specific antibodies (4). Both of these are self-con- tained tests that can be performed out of the laboratory, need a minimum of equipment, and give immediate results. Inter- leukin-10 (IL-10) has also been proposed as a potential marker for stage determination, because high serum and CSF IL-10 concentrations have been observed in patients with the menin- * Corresponding author. Mailing address: Institute of Tropical Med-
Medical records of enrolled patients were retrospectively reviewed. Patients ’ demographic data (such as sex, age, height and weight), types of cancer, technical data (such as insertion interspace, catheter tip location), complications related to IMITPP were obtained from the medical records. Numerical pain rating scales (NRS) scores, Karnofsky per- formance scores (KPS), and doses of opioids before and after IMITPP were also determined. Costs before IMITPP (pre- IMITPP) were calculated based on the types and doses of systemic opioids on admission, including professional fee and costs of systemic opioids. Costs after IMITPP (post- IMITPP) were calculated based on the doses of intrathecal morphine at discharge, including professional fee, rental of the external drug infusion pump, costs of medication (mor- phine hydrochloride injection and 0.9% sodium chloride solution) and disposable wound care pack. The total implan- tation costs were determined as the total hospitalization expense, which included the costs of subcutaneous port and medication, ward fee, laboratory fee, image examination fee, anesthetic fee and operation fee.
Study involves adult patients aged between 18 – 60 years, ASA grade 1 and 2 posted for lower abdominal surgeries.Patients were randomly divided into two groups group A ,B,C ,group A received intrathecal neostigmine 50 micrograms with 2.5 ml of 0.5% hyperbaric bupivacaine and group B received 50 micrograms of clonidine with 2.5ml of 0.5% hyperbaric bupivacainegroup C received plain hyperbaric bupivacaine 0.5% 2.5 ml.On the day of surgery IV line secured with 18G cannula, IV midazolam 1mg given as premedication. Patients connected to multiparamonitor showing ECG, PR ,NIBP and SPO 2 and basal readings recorded. All patients are preloaded with IV fluids of 10 ml/kg .Under strict aseptic precautions lumbar puncture performed at L3- L4 space using 25 G spinal needle in right lateral position, the study drugs are injected into subarachnoid space at the rate of 1ml/3 sec. Patient turned supine immediately and supplemental oxygen given.
In man opiates have been used successfully chiefly in the treatment of chronic pain, post-operative and obstetric pain. Neither analgesia nor side effects are likely to result from systemic absorption of spinally administered opioids. Intrathecal morphine is effective in a dose well below that required for systemic effects while analgesic effect generally correlates poorly with plasma concentration following epidural fentanyl, pethidine and morphine.
Since morphine was first injected into the spinal fluid to treat cancer pain in 1979, there have been innovations in IDDS as well as the breadth of medications delivered to the intrathecal space for control of pain and spasticity. Delivering medications intrathecally allows for signifi- cantly reduced doses compared with oral therapy, along with a reduction in the adverse effects associated with oral or parenteral delivery of analgesics. Recent consensus guidelines provide lines of therapy with agents such as morphine, ziconotide, clonidine, and bupivacaine based on nociceptive, neuropathic, or mixed pain conditions. Most experts believe that IDDS can be quite effective for a smaller subset of patients with cancer, noncancer, and spasticity- induced pain. Further, trialing patients prior to implantation is generally recommended, but may be less necessary for patients suffering from cancer pain. The data emphasize the value of intrathecal therapy for cancer pain in terms of pain relief, reduction in adverse effects, and cost-effectiveness. The evidence is less clear for long-term relief in noncancer pain other than spasticity, although the cost-effectiveness data support its use within approximately 12–24 months compared with traditional therapies. Implanting physicians should be mindful of the need to monitor fluctuations in selected serum hormones, especially with intrathecal opi- oids as well as the potential for development of granuloma. Studies in progress with novel intrathecal agents coupled with advanced IDDS technology offer promise for more complete pain relief, enhanced safety, and better long-term outcomes in terms of quality of life.
Hyperbaric solutions are mostly used in this method since, they have a more rapid onset duration, Marcaine 0.5 % being the most commonly used. This drug usually produces sensory, motor and somatic block in about 9-10 minutes of intrathecal injection [1-3]. Using additives such as clonidine, morphine, fentanyl and sufentanil creates a more rapid block with more superior block quality [4-5].
for use in evaluating patients as candidates for advanced pain management interventions such as intrathecal (IT) therapy states that “Pain is defined as refractory, regardless of etiol- ogy, when 1) multiple evidence-based biomedical therapies used in a clinically appropriate and acceptable fashion have failed to reach treatment goals that may include adequate pain reduction and/or improvement in daily functioning or have resulted in intolerable adverse effects, and when 2) psychiatric disorders and psychosocial factors that could influence pain outcomes have been assessed and appropri- ately addressed”. 8
Explanation of the differences in our findings from the earlier demonstration of increased IT IgG Synthesis with IFN-α treatment reflect at least two possible factors, op- erating separately or together: 1) relapsing-remitting pa- tients have fundamentally different biological processes than progressive disease, [14,15] and, 2) the synthetic interferon products differ in many respects from the highly purified natural products [16,17]. Numerous ob- servations support the first explanation. However, the presence of 18 different fully glycosylated forms of in- terferons alpha, that comprises the natural product, may well provide an alternative explanation. Certainly, im- mune responses to “contaminants” like C1q in natural IFN-α  could contribute to benefit from the product, or may decrease any benefit.