Paradoxical reaction in tuberculous meningitis: presentation, predictors and impact on prognosis.

BACKGROUND: Awareness about paradoxical reactions in tuberculous meningitis is crucial as a paradoxical reaction may lead to certain wrong conclusions (for example, an erroneous diagnosis, and a possibility of treatment failure, mycobacterial drug-resistance, drug toxicity, or presence of a malignancy). The present study was planned to evaluate the incidence and predictive factors of paradoxical reactions in light of clinical, cerebrospinal fluid, and neuroimaging characteristics. METHODS: In this prospective cohort study, consecutive patients fulfilling the International Consensus criteria of tuberculous meningitis were included. Patients were subjected to clinical evaluation, cerebrospinal fluid evaluation, and neuroimaging. Patients were treated with anti-tuberculosis drugs along with corticosteroids. Patients were regularly followed up at 3 monthly intervals. At each follow up patients were evaluated clinically and repeat cerebrospinal fluid analysis was performed along with repeat neuroimaging. Disability assessment was done using Barthel index. RESULTS: We enrolled 141 patients of tuberculous meningitis. Approximately one-third of patients (44/141; 31.2 %) developed a paradoxical reaction. Twenty-seven patients developed hydrocephalus, 26 developed tuberculomas, 12 developed optochiasmatic arachnoiditis and 4 patients had spinal arachnoiditis. In 41 patients (out of 44) cerebrospinal fluid paradoxically worsened (increase in cells and/or protein); 2 demonstrated a decrease in cells with polymorph predominance while in one it was normal. In 3 patients, paradoxical cerebrospinal fluid changes were not associated with neuroimaging changes. On multivariate analysis, predictors of paradoxical reaction were female gender (p = 0.013), HIV positivity (p = 0.01) and a shorter duration of illness (p = 0.049). Development of paradoxical reactions did not predict the disability status of the patients. CONCLUSIONS: Paradoxical reaction occurs in approximately one-third of patients with tuberculous meningitis. Female gender, concomitant HIV infection, and a shorter duration of illness were significant predictors. Paradoxical reactions did not adversely affect the outcome.

Clinical findings for fungal infections caused by methylprednisolone injections.

BACKGROUND: Since September 18, 2012, public health officials have been investigating a large outbreak of fungal meningitis and other infections in patients who received epidural, paraspinal, or joint injections with contaminated lots of methylprednisolone acetate. Little is known about infections caused by Exserohilum rostratum, the predominant outbreak-associated pathogen. We describe the early clinical course of outbreak-associated infections. METHODS: We reviewed medical records for outbreak cases reported to the Centers for Disease Control and Prevention before November 19, 2012, from the six states with the most reported cases (Florida, Indiana, Michigan, New Jersey, Tennessee, and Virginia). Polymerase-chain-reaction assays and immunohistochemical testing were performed on clinical isolates and tissue specimens for pathogen identification. RESULTS: Of 328 patients without peripheral-joint infection who were included in this investigation, 265 (81%) had central nervous system (CNS) infection and 63 (19%) had non-CNS infections only. Laboratory evidence of E. rostratum was found in 96 of 268 patients (36%) for whom samples were available. Among patients with CNS infections, strokes were associated with an increased severity of abnormalities in cerebrospinal fluid (P<0.001). Non-CNS infections were more frequent later in the course of the outbreak (median interval from last injection to diagnosis, 39 days for epidural abscess and 21 days for stroke; P<0.001), and such infections developed in patients with and in those without meningitis. CONCLUSIONS: The initial clinical findings from this outbreak suggest that fungal infections caused by epidural and paraspinal injection of a contaminated glucocorticoid product can result in a broad spectrum of clinical disease, reflecting possible variations in the pathogenic mechanism and in host and exposure risk factors. (Funded by the Centers for Disease Control and Prevention.).

Lumbar arachnoiditis and thecaloscopy: brief review and proposed treatment algorithm.

The term arachnoiditis describes the inflammation of the meninges and subarachnoid spaces. Lumbar arachnoiditis is characterized by obliterated nerve root sleeves and the adherence of nerve roots to each other in the proximity of the cauda equina, and may be secondary to infectious diseases or tumors, iatrogenic (subsequent to spinal surgery) or idiopathic. It is not very clearly defined epidemiologically or clinically, and various theories regarding its pathophysiology have been proposed; furthermore, its treatment is difficult because there is a lack of evidence-based diagnostic and therapeutic gold standards. Thecaloscopy has been recently described as a novel technique for retrograde transcutaneous neuroendoscopic inspection of the subarachnoid structures of the lumbar thecal sac; it has also been suggested for the treatment of lumbar arachnoiditis. We here review the most modern techniques for the treatment of this disease such as thecaloscopy and neurostimulation.

Neurologic deficits and arachnoiditis following neuroaxial anesthesia.

Of late, regional anesthesia has enjoyed unprecedented popularity; this increase in cases has brought a higher frequency of instances of neurological deficit and arachnoiditis that may appear as transient nerve root irritation, cauda equina, and conus medullaris syndromes, and later as radiculitis, clumped nerve roots, fibrosis, scarring dural sac deformities, pachymeningitis, pseudomeningocele, and syringomyelia, etc., all associated with arachnoiditis. Arachnoiditis may be caused by infections, myelograms (mostly from oil-based dyes), blood in the intrathecal space, neuroirritant, neurotoxic and/or neurolytic substances, surgical interventions in the spine, intrathecal corticosteroids, and trauma. Regarding regional anesthesia in the neuroaxis, arachnoiditis has resulted from epidural abscesses, traumatic punctures (blood), local anesthetics, detergents, antiseptics or other substances unintentionally injected into the spinal canal. Direct trauma to nerve roots or the spinal cord may be manifested as paraesthesia that has not been considered an injurious event; however, it usually implies dural penetration, as there are no nerve roots in the epidural space posteriorly. Sudden severe headache while or shortly after an epidural block using the loss of resistance to air approach usually suggests pneumocephalus from an intradural injection of air. Burning severe pain in the lower back and lower extremities, dysesthesia and numbness not following the usual dermatome distribution, along with bladder, bowel and/or sexual dysfunction, are the most common symptoms of direct trauma to the spinal cord. Such patients should be subjected to a neurological examination followed by an MRI of the effected area. Further spinal procedures are best avoided and the prompt administration of IV corticosteroids and NSAIDs need to be considered in the hope of preventing the inflammatory response from evolving into the proliferative phase of arachnoiditis.

Tuberculous radiculomyelitis (arachnoiditis): myelographic (and CT myelographic) appearances.

Tuberculous radiculomyelitis (arachnoiditis) remains one of the important causes of paraplegia in India. The diagnosis usually rests on clinical history and examination, and on laboratory findings in the cerebro-spinal fluid (CSF). Few descriptive reports are available of the myelographic appearance, with water-soluble contrast media, in tuberculous radioculomyelitis (arachnoiditis). A retrospective review of 21 myelograms and 10 computed tomographic (CT) myelograms, in 14 patients with tuberculous radiculomyelitis, was carried out, with a view to describing, in detail, the radiographic features. An attempt was made to assess the use of the radiologic procedures in diagnosis and follow up in these patients. Conventional myelographic findings included block (8/14), irregular subarachnoid space (9/14), filling defects (8/14), sluggish contrast flow (2/14), root thickening (3/14) and atrophic cord (2/14). Computed tomographic myelography showed reduced contrast density in portions of the opacified CSF ring around the cord in affected region (6/7) and, in addition, demonstrated septa and adhesions. Intravenous contrast CT was not found to be useful (2/2). Follow-up studies showed partial resolution (3/6), deterioration (1/6) and status quo of radiological findings (2/6). Although these changes can be seen in chronic radiculomyelitis (arachnoiditis) from other causes, such as leukaemic infiltration/lymphoma, other chronic central nervous system infections and iatrogenic causes, including repeated intrathecal injections, conventional myelography appeared to be useful for diagnosis and follow up in tuberculous radiculomyelitis (arachnoiditis).

Adhesive arachnoiditis after lumbar myelography.

Of 1500 myelographies, 99 patients had subsequent myelographies from which the prevalence of adhesive arachnoiditis caused by the initial investigation could be calculated. Three different water-soluble contrast agents had been used in the initial study: Kontrast U (800 patients), Dimer-X (400 patients), and Conray (300 patients) and the subsets of patients restudied represented 6%, 8% and 8% respectively of the whole series. After the first myelography 68 patients had no operation, 31 patients had hemilaminectomy. Conray produced arachnoid changes in 71% of the nonoperated patients. This differed significantly from the 43% caused by Kontrast U, and the 27% evoked by Dimer-X. The same trend was evident in the operated subset. The severity of the arachnoid changes was greater after Conray. Analysis of the iodine content of the different contrast media and comparison with similar series suggested that hyperosmolarity of the agent was responsible for the changes.