Category Archives: Infection

Update: Spinal instrumentation infection

Spinal instrumentation infection

Instrumentation has become an integral component in the management of various spinal disorders. The rate of infection varies from 2% to 20% of all instrumented spinal procedures.

Surgical site infection (SSI) in the spine is a serious postoperative complication. Factors such as posterior surgical approach, arthrodesis, use of spinal instrumentation, age, obesity, diabetes, tobacco use, operating-room environment and estimated blood loss are well established in the literature to affect the risk of infection 1).

Diagnosis

There are multiple risk factors for postoperative spinal infections. Infections in the setting of instrumentation are more difficult to diagnose and treat due to biofilm. Infections may be early or delayed. C Reactive Protein (CRP) and Magnetic Resonance Imaging (MRI) are important diagnostic tools. 2).


Blood specimens were obtained from patients who underwent posterior decompression, instrumentation with pedicular screws, and posterolateral fusion from June 2009 to January 2011. CRP and ESR levels were measured on the day before surgery and on postoperative days 1, 3, 7, 11, 14, 28, and 42.

Mean CRP levels peaked on the third day postoperatively in all groups. By day 7 postoperatively, it had dropped rapidly. At the 14th and 28th postoperative days, decreases to normal CRP levels were found in 16% and 80% of all patients, respectively. The pattern of decline in CRP was similar among groups. Values of ESR increased and peaked between the third and seventh postoperative days. ESR values gradually decreased. At the 42 day postoperatively, ESR level still remain above normal values in all groups 3).


MRI is a useful tool for the early diagnosis of a deep SSI. However, the diagnosis is frequently difficult with feverish patients with clear wounds after posterior spinal instrumentation (PSI) because of artifacts from the metallic implants. There are no reports on MRI findings that are specific to a deep SSI after PSI.

Kimura et al. found that fluid collection outside the head of the PS on an axial MRI scan (PS fluid sign) strongly suggested the possibility of an abscess.

The SSI group comprised 17 patients with a deep SSI after posterior lumbar spinal instrumentation who had undergone an MRI examination at the onset of the SSI. The non-SSI group comprised 64 patients who had undergone posterior lumbar spinal instrumentation who did not develop an SSI and had an MRI examination within 4 weeks after surgery. The frequency of a positive PS fluid sign was compared between both groups.

The PS fluid sign had a sensitivity of 88.2%, specificity of 89.1%, positive predictive value of 68.1%, and negative predictive value of 96.6%. The 2 patients with a false-negative PS fluid sign in the SSI group had an infection at the disk into which the interbody cage had been inserted. Three of the 7 patients with a false-positive PS fluid sign in the non-SSI group had a dural tear during surgery.

The PS fluid sign is a valuable tool for the early diagnosis of a deep SSI. The PS fluid sign is especially useful for diagnosing a deep SSI in difficult cases, such as feverish patients without wound discharge 4).

Treatment

Optimal results are obtained with surgical debridement followed by parenteral antibiotics.

Until today the role of spinal instrumentation in the presence of a wound infection has been widely discussed and recently many authors leave the hardware in place with appropriate antibiotic therapy 5).

Removal or replacement of hardware should be considered in delayed infections.

An improved understanding of the role of biofilm and the development of newer spinal implants has provided insight in the pathogenesis and management of infected spinal implants. It is important to accurately identify and treat postoperative spinal infections. The treatment is often multimodal and prolonged 6).

Evidence based medicine

In a study, from the Department of Neurosurgery, Northwestern University Feinberg School of Medicine, Chicago, USA evidence based medicine was used to assess optimal surgical and medical management of patients with post-operative deep wound infection following spinal instrumentation. A computerized literature search of the PubMed database was performed. Twenty pertinent studies were identified. Studies were separated into publications addressing instrumentation retention versus removal and publications addressing antibiotic therapy regimen. The findings were classified based on level of evidence (I-III) and findings were summarized into evidentiary tables.

No level of evidence 1 or level of evidence 2 was identified. With regards to surgical management, five studies support instrumentation retention in the setting of early deep infection. In contrast, for delayed infection, the evidence favors removal of instrumentation at the time of initial debridement. Surgeons should be aware that for deformity patients, even if solid fusion is observed, removal of instrumentation may be associated with significant loss of correction. A course of intravenous antibiotics followed by long-term oral suppressive therapy should be pursued if instrumentation is retained. A shorter treatment course may be appropriate if hardware is removed 7).


The objective of a study was to investigate the morbidity and mortality associated with instrumented fusion in the setting of primary spinal infection.

A search was performed in the PubMed and Medline databases for clinical case series describing instrumented fusion in the setting of primary spinal infection between 2003 and 2013. The search was limited to the English language and case series including at least 20 patients. The primary outcome measure was postoperative infection (recurrent local infection) + surgical site infection (SSI); secondary outcome measures included reoperation rates, development of other complications, and perioperative mortality.

There were 26 publications that met the inclusion criteria, representing 931 patients with spondylodiscitis who underwent decompression, debridement, and instrumented fusion. Spinal infections occurred most commonly in the lumbosacral spine (39.1%) followed by the thoracic spine (27.1%). The most common microorganisms were Staphylococcus spp. After decompression, debridement, and instrumented fusion, the overall rate of postoperative infection was 6.3% (1.6% recurrent infection rate + 4.7% SSI rate). The perioperative complication rate was 15.4%, and the mortality rate was estimated at 2.3%. Reoperation for wound debridement, instrumentation removal, pseudoarthrosis, and/or progressive neurological deficit was performed in 4.5% of patients.

The findings in this literature review suggest that the addition of instrumentation in the setting of a primary spinal infection has a low local recurrent infection rate (1.6%). However, the combined risk of postoperative infection is 6.3% (recurrent infection + SSI), more than three-fold the current infection rate following instrumentation procedures for degenerative spine disease. Moreover, the addition of hardware does usher in complications such as instrumentation failure and pseudoarthrosis requiring reoperation 8).

Case series

2017

A retrospective, cohort study of 84 patients with deep spine infection managed at a major tertiary hospital over 14 years with a minimum follow up of 2 years.

It is often believed that implants should not be inserted in patients with deep spine infection because of the risk of persistent or recurrent infection. However, there are often concerns about spinal stability and a paucity of evidence to guide clinical practice in this field.

Dennis et al. compared the mortality, reoperation, and reinfection rates in patients with spine infection treated with antibiotics alone, antibiotics with debridement, and antibiotics with debridement and instrumentation. Significant outcome predictors were determined using multivariable logistic regression model.

Forty-nine males and 35 females with a mean age was 62.0 years had spine infection affecting the lumbar spine predominantly. The most common form of infection was osteomyelitis and spondylodiscitis (69.4%). Staphylococcus aureus was the most common causative organism (61.2%).There was no difference in terms of reoperation or relapse for patients treated with antibiotics alone, antibiotics with debridement, or antibiotics with debridement and instrumentation. However, compared with antibiotics alone, the crude inhospital mortality was lower for patients treated with instrumentation (odds ratio, OR, 0.82; P = 0.01), and antibiotics with debridement (OR 0.80; P = 0.02).

Spinal instrumentation in an infected spine is safe and not associated with higher reoperation or relapse rates. Mortality is lower for patients treated with instrumentation 9).


A retrospective review of patients with MRSE-related SSIs from 665 consecutive cases of SI surgery performed between 2007 and 2014

During the study period, SSIs occurred in 21 patients. MRSE was isolated from cultures obtained from surgical wounds in nine of the 21 patients (43%). There were four males and five females with a mean age of 63.9 ± 15.1 years. Six patients presented with inflammatory signs, such as wound drainage, pyrexia, erythema, and elevated C-reactive protein. Three patients did not have signs of infection, but had early implant failure, and were diagnosed by positive cultures collected at the time of revision surgery. The mean time from index surgery to the diagnosis of infection was 23.6 days (range, 7-88 days). In one patient, the implant was removed before antibiotic treatment was administered because of implant failure. Eight patients were managed with antibiotics and implant retention. During the follow-up period, MRSE-related SSIs in seven of the eight patients were resolved with implant retention and antibiotics without the need for further surgical intervention. One patient did not complete the antibiotic course because of side effects, and implant removal was required to control the infection.

Early detection, surgical debridement, and administration of appropriate antibiotics for a suitable duration enabled infection control without the need for implant removal in the treatment of MRSE-related SSI after SI surgery 10).


Eleven patients with SSI after undergoing spinal surgery involving instrumentation were studied. All had been refractory to conventional treatments, including intravenous antibiotic administration and conventional debridement and irrigation. Antibiotic-loaded bone cement was placed on and around the instrumentation to cover them and to occupy the surrounding dead space. Two general types of antibiotics were loaded into the polymethylmethacrylate bone cement. The recipes for the mixture were changed depending on the bacterial cultures. Sensitive antibiotics were administered generally for 2-6 weeks until the C-reactive protein level was normalized.

All patients were treated successfully using antibiotic-loaded bone cement. Only 1 patient needed a repeat of this procedure to treat an infection. Antibiotic-loaded bone cement was placed in situ in all patients during the follow-up period and there were no significant adverse events.

Antibiotic-loaded bone cement treatment reduces the dead space and achieves the targeted drug delivery simultaneously. Treatment using antibiotic-loaded bone cement is an effective treatment option for complex spinal SSI 11).


Between 2010 and 2015, 12 out of 514 patients who developed a deep infection after spinal surgery, were selected and reviewed retrospectively at multiple centers (MGM Hospital, Kamothe and Center for Orthopaedic & Spine Surgery, New Panvel, Navi Mumbai, India). Out of 12 patients, one of the patients needed a partial implant exchange although none of the cases needed complete implant removal. All patients had achieved clean closed wounds along with a retention of the instrumentation. There was no need for flap surgery to cover wound defect in any case. However, antibiotic treatment was necessary in all cases. None of the patients showed a new infection after the treatment.

The study demonstrates the usefulness of VAC therapy as an alternative management for wound conditioning of a back wound with the high complexity in nature after instrumented spine surgeries as it eliminates complex secondary surgeries, prolong use of antibiotics and removal of the implants 12).

2015

A retrospective database review of consecutive patients with traditional open lumbar spinal surgery was performed. SSIs patients were identified and reviewed for clinically relevant details, and postoperative SSIs’ incidence was calculated for the entire cohort as well as for subgroups with or without spinal implants. In 15 years, 1,176 patients underwent open lumbar spinal surgery with spinal implants and 699 without. Thirty-eight developed postoperative SSIs. Total SSI rate for the entire group was 2.03%. The incidence of postoperative SSIs in the nonimplant group was relatively low. Patients received antibiotics, hyperbaric oxygen therapy, and wet dressing.

Liu et al. provided the precise rates of postoperative SSIs in traditional open spinal surgery obtained from a single-centre data. Patients with spinal implants had higher SSIs’ incidence than those without 13).

2014

Thirty-six patients underwent only decompression, and 82 underwent decompression and instrumented fusion. In the decompression-only group, 8.33% of patients had continued osteomyelitis/discitis compared with 9.76% of patients in the instrumented group (P = 0.807). Importantly, the reoperation rate was also similar between the decompression-only group (19.44%) and the instrumented group (17.07%; P = 0.756). Similarly, subanalyses based on infection location revealed no significant increase in rates of recurrent infection or reoperation in patients who underwent instrumentation 14).


Patients who received just decompression for spinal infection had similar reoperation and continued infection rates as patients who additionally underwent instrumentation, irrespective of infection location within the spine. These findings suggest that instrumentation of the infected spine may be a safe treatment modality and should be considered when the spinal integrity is compromised 15).

2008

A 10-year retrospective audit. (1) The incidence of infection; (2) causative organisms; (3) whether eradication of infection is achievable with spinal implant retention; (4) patient outcome. The reported incidence of infection following posterior spinal instrumentation is between 2.6 and 3.8%. Management of infection is controversial, with some advocating serial wound debridement while others report that infection cannot be eradicated with retention of implants. There are no published data demonstrating that propionibacteria are associated with early postoperative infection. The management of infected cases at our institution includes eventual removal of their implants. Our population was identified by studying the case notes of all patients who had undergone removal of spinal implants and cross-referencing this population with positive microbiology or histology reports. The incidence of infection was 3.7%. Propionibacteria were isolated in 45% of cases. The diagnosis of infection was unexpected in 25% of patients, following removal of implants for prominence of implants or back pain. Sixty per cent of patients with acute postoperative deep wound infection had continuing active infection on subsequent removal of implants, despite long-term antibiotics and wound debridement. Fourty-six per cent of patients had a stable, pain-free spine at the end of their treatment. This is the largest reported series of infections following posterior spinal instrumented fusions of which we are aware. Propionibacteria are a common cause of infection and successful eradication of infection cannot be reliably achieved with antibiotics and wound debridement alone 16).

1997

Twenty-three of 238 patients (9.7%) developed wound infections following segmental spinal instrumentation. When the infected group and a matched control group were compared, the infected group had a significantly higher number of patients with cerebral palsy and myelodysplasia (nonambulatory), patients with wound hematomas, patients with fusions that extended into the sacral region, and patients who were incontinent of urine. A high incidence of infections with gram-negative aerobic bacilli correlated with the extension of the surgery into the sacral region and bowel and/or bladder incontinence. Prophylactic antibiotics with broader coverage for gram-negative bacilli may be warranted for these procedures. Postoperative wound infections were managed by surgical drainage and debridement as well as antibiotics. Removal of the hardware was not necessary to control the infection in these patients who underwent segmental spinal instrumentation 17).

1)

Gerometta A, Rodriguez Olaverri JC, Bitan F. Infections in spinal instrumentation. Int Orthop. 2012 Feb;36(2):457-64. doi: 10.1007/s00264-011-1426-0. Epub 2012 Jan 5. Review. PubMed PMID: 22218913; PubMed Central PMCID: PMC3282865.

2) , 6)

Kasliwal MK, Tan LA, Traynelis VC. Infection with spinal instrumentation: Review of pathogenesis, diagnosis, prevention, and management. Surg Neurol Int. 2013 Oct 29;4(Suppl 5):S392-403. doi: 10.4103/2152-7806.120783. eCollection 2013. PubMed PMID: 24340238; PubMed Central PMCID: PMC3841941.

3)

Kunakornsawat S, Tungsiripat R, Putthiwara D, Piyakulkaew C, Pluemvitayaporn T, Pruttikul P, Kittithamvongs P. Postoperative Kinetics of C-Reactive Protein and Erythrocyte Sediment Rate in One-, Two-, and Multilevel Posterior Spinal Decompressions and Instrumentations. Global Spine J. 2017 Aug;7(5):448-451. doi: 10.1177/2192568217699389. Epub 2017 Apr 11. PubMed PMID: 28811989; PubMed Central PMCID: PMC5544159.

4)

Kimura H, Shikata J, Odate S, Soeda T. Pedicle Screw Fluid Sign: An Indication on Magnetic Resonance Imaging of a Deep Infection After Posterior Spinal Instrumentation. Clin Spine Surg. 2017 May;30(4):169-175. doi: 10.1097/BSD.0000000000000040. PubMed PMID: 28437330.

5)

Dobran M, Mancini F, Nasi D, Scerrati M. A case of deep infection after instrumentation in dorsal spinal surgery: the management with antibiotics and negative wound pressure without removal of fixation. BMJ Case Rep. 2017 Jul 28;2017. pii: bcr-2017-220792. doi: 10.1136/bcr-2017-220792. PubMed PMID: 28756380.

7)

Lall RR, Wong AP, Lall RR, Lawton CD, Smith ZA, Dahdaleh NS. Evidence-based management of deep wound infection after spinal instrumentation. J Clin Neurosci. 2015 Feb;22(2):238-42. doi: 10.1016/j.jocn.2014.07.010. Epub 2014 Oct 11. Review. PubMed PMID: 25308619.

8)

DE LA Garza-Ramos R, Bydon M, Macki M, Abt NB, Rhee J, Gokaslan ZL, Bydon A. Instrumented fusion in the setting of primary spinal infection. J Neurosurg Sci. 2017 Feb;61(1):64-76. Epub 2015 Apr 15. Review. PubMed PMID: 25875732.

9)

Dennis Hey HW, Nathaniel Ng LW, Tan CS, Fisher D, Vasudevan A, Liu KG, Thambiah JS, Kumar N, Lau LL, Wong HK, Tambyah PA. Spinal Implants Can Be Inserted in Patients With Deep Spine Infection: Results From a Large Cohort Study. Spine (Phila Pa 1976). 2017 Apr 15;42(8):E490-E495. doi: 10.1097/BRS.0000000000001747. PubMed PMID: 27333342.

10)

Takizawa T, Tsutsumimoto T, Yui M, Misawa H. Surgical Site Infections Caused by Methicillin-resistant Staphylococcus epidermidis After Spinal Instrumentation Surgery. Spine (Phila Pa 1976). 2017 Apr 1;42(7):525-530. doi: 10.1097/BRS.0000000000001792. PubMed PMID: 27428392.

11)

Masuda S, Fujibayashi S, Otsuki B, Kimura H, Matsuda S. Efficacy of Target Drug Delivery and Dead Space Reduction Using Antibiotic-loaded Bone Cement for the Treatment of Complex Spinal Infection. Clin Spine Surg. 2017 Jul 7. doi: 10.1097/BSD.0000000000000567. [Epub ahead of print] PubMed PMID: 28692571.

12)

Kale M, Padalkar P, Mehta V. Vacuum-Assisted Closure in Patients with Post-operative Infections after Instrumented Spine Surgery: A Series of 12 Cases. J Orthop Case Rep. 2017 Jan-Feb;7(1):95-100. doi: 10.13107/jocr.2250-0685.706. PubMed PMID: 28630851; PubMed Central PMCID: PMC5458710.

13)

Liu JT, Liao WJ, Chang CS, Chen YH. Management of Deep Infection after Instrumentation on Lumbar Spinal Surgery in a Single Institution. Biomed Res Int. 2015;2015:842010. doi: 10.1155/2015/842010. Epub 2015 Jul 26. PubMed PMID: 26273650; PubMed Central PMCID: PMC4529929.

14) , 15)

Bydon M, De la Garza-Ramos R, Macki M, Naumann M, Sciubba DM, Wolinsky JP, Bydon A, Gokaslan ZL, Witham TF. Spinal Instrumentation in Patients with Primary Spinal Infections Does Not Lead to Greater Recurrent Infection Rates: An Analysis of 118 Cases. World Neurosurg. 2014 Jun 14. pii: S1878-8750(14)00560-9. doi: 10.1016/j.wneu.2014.06.014. [Epub ahead of print] Review. PubMed PMID: 24937598.

16)

Collins I, Wilson-MacDonald J, Chami G, Burgoyne W, Vineyakam P, Berendt T, Fairbank J. The diagnosis and management of infection following instrumented spinal fusion. Eur Spine J. 2008 Mar;17(3):445-450. doi: 10.1007/s00586-007-0559-8. Epub 2007 Dec 13. Erratum in: Eur Spine J. 2017 Jul 20;:. PubMed PMID: 18075763; PubMed Central PMCID: PMC2270376.

17)

Perry JW, Montgomerie JZ, Swank S, Gilmore DS, Maeder K. Wound infections following spinal fusion with posterior segmental spinal instrumentation. Clin Infect Dis. 1997 Apr;24(4):558-61. PubMed PMID: 9145726.

Update: Cladophialophora bantiana

Cladophialophora bantiana

Cladophialophora bantiana is a dematiaceous fungus with a predilection for causing central nervous system (CNS) infection manifesting as brain abscess.

Immunocompromised individuals with organ transplantations and AIDS are susceptible to acquire the fungal infection, particularly in brain or meninges. However, primary cerebral phaeohyphomycosis caused by C. bantiana appears to be an exception to this rule, occurring more commonly in immunocompetent than in immunocompromised patients 1).

Epidemiology

It is the most frequently isolated species from cerebral phaeohyphomycosis. It mostly affects adult men in the second and third decade of life 2).

In the Grant Medical College and Sir J. J. Hospital, Mumbai, India, Forty-one (54.70%) abscesses were found to be due to pyogenic organisms, 4% due to Mycobacterium tuberculosis and 1.3% were due to Cladophialophora bantiana 3).

Diagnosis

There is no initial clinical or laboratory feature that makes a preoperative diagnosis possible and relies on microbiological confirmation 4).

Treatment

Successful treatment depends on obtaining a complete surgical resection, an accurate microbiological diagnoses for mold identification, and an effective long-term, personalized antifungal treatment. Close radiographic surveillance is necessary to ensure complete eradication 5).


C. bantiana tends to be resistant to amphotericin B. Accordingly, Al-Abdely et al. evaluated amphotericin B and three triazoles–posaconazole, itraconazole, and fluconazole–for treatment of C. bantiana infection in mice. In immunosuppressed ICR mice infected intravenously, posaconazole, itraconazole, and amphotericin B prolonged survival. This improvement in survival corresponded with a reduction in brain fungal concentrations for mice which were given itraconazole and posaconazole, but not amphotericin B. In nonimmunosuppressed BALB/c mice infected intracerebrally, posaconazole showed dose-dependent responses in survival and reduction of brain tissue counts. These responses were observed for short, delayed, and prolonged therapy. Although posaconazole prolonged the survival of mice with reductions in brain fungal counts, it did not sterilize brain tissue with continuous therapy for 8 weeks. They concluded that posaconazole shows promise for the treatment of C. bantiana brain infections 6).

Outcome

It may carry up to a 70% mortality rate despite advances in surgical resection capabilities and the use of both systemic and intrathecal antifungal treatments 7).

The outcome is better in patients with abscess. Excision of the abscess followed by combination antifungal therapy results in better outcome. Close follow-up is required due to high risk of recurrence 8).

Reviews

Dash C, Kumar A, Doddamani RS. Is complete excision the key to cure for Cladophialophora bantiana brain abscess? A review of literature. Neurol India. 2016 Sep-Oct;64(5):1062-4. doi: 10.4103/0028-3886.190250. PubMed PMID: 27625264. 9)


Chakrabarti et al. reviewed 124 culture proven C. bantiana brain abscess cases; 103 cases published in English literature during 1952 through 2014 and 21 unpublished cases from the Postgraduate Institute of Medical Education and Research, Chandigarh, India. The majority (57.3%) of the patients was from Asian countries especially from India (62/124, 50%). The diagnosis of the cases was delayed with mean duration 115 days after developing symptoms. The disease was nearly equally distributed in immunocompetent and immunosuppressed hosts but associated with significantly higher mortality (77.1%) in later group. Complete excision of brain lesion in immunocompetent host led to significantly better survival (43.7%). Though all commercially available antifungal drugs have been used in these patients, amphotericin B deoxycholate or lipid preparations were most commonly (62.83%) prescribed agent. None of the drugs used was found to be independently associated with improved outcome. In vitro antifungal susceptibility testing of 13 isolates of our center, demonstrated good activity to voriconazole, posaconazole, and itraconazole, but these triazoles were prescribed in only 29.2% patients. Increased awareness with early suspicion of the disease, and aggressive medical and surgical approach in treating these patients may improve the outcome 10).

Case series

2017

At the Geisinger Health System, Danville, Pennsylvania, the patients’ cases presented with raised intracranial features of headache, visual field cut, and/or memory loss, with a correspondingly wide variety of radiological differential diagnoses. It was the microbiological, histopathological, and genomic identification of C. bantiana that ensured targeted, individualized patient therapies.

Successful treatment depends on obtaining a complete surgical resection, an accurate microbiological diagnoses for mold identification, and an effective long-term, personalized antifungal treatment. Close radiographic surveillance is necessary to ensure complete eradication of pheoid fungi11).

2007

A retrospective study of 10 patients with CNS cladosporiosis managed at National Institute of Mental Health and Neurosciences from 1979 to 2006. It is a descriptive study. The case records were reviewed for clinical presentation, radiological features, management and outcome. Only those patients in whom the fungus could be isolated on culture were included in the study.

The age of the patients ranged from three to 42 years. Nine patients presented with features of space-occupying lesion and one patient with chronic meningitis. There were no specific clinical or radiological features. None of patients had impaired immune status. This infection presented as two pathomorphological forms – diffuse meningoencephalitis and focal abscesses. Burr hole tapping and excision are the surgical options. Both patients with burr hole tapping required excision of abscess subsequently. Two out of seven patients with abscess expired compared to all three patients with diffuse meningoencephalitis who expired. Recurrences occurred in four of the five patients following excision of the abscess. Combination antifungal treatment had better result than monotherapy. The outcome was poor with survival of only 50%.

Thorough microbiological examination is required to diagnose CNS infection caused by C. bantiana. The outcome is better in patients with abscess. Excision of the abscess followed by combination antifungal therapy results in better outcome. Close follow-up is required due to high risk of recurrence 12).

Case reports

2017

A 55-year-old diabetic male presented with severe headache, blurred-vision, behavioural abnormalities, eye-pain and ear-discharge. He was undergoing treatment for hypertension, prostatomegaly and obstructive pulmonary disease. He was on steroids for the past six years for uveitis. Haematology reports indicated elevated WBC and platelet count. He was negative for HIV, hepatitis, autoimmune antibodies and tumour markers. CD4 count was within normal limits. Brain magnetic resonance imaging revealed multiple ring-enhancing lesions and oedema in the left tempero-parietal region. Chest X-ray showed irregular consolidations in right paracardiac region and confluence in both lungs. Positron Emission Tomography of whole body revealed multiple lesions in brain, lungs, lymph nodes and C3-vertebrae. Histopathology of the lung lesion showed non-tuberculous infectious pathology and brain lesions showed necrosis with occurrence of pigmented hyphal fungi. The pus aspirated during surgical excision of brain lesions grew black mold, identified as C. bantiana. Although patient was started on intravenous Voriconazole, he succumbed to the infection after 7 days. The lesion was initially suspected to be of tuberculous etiology, and the lesions in lungs were also suggestive of malignancy, which was however ruled out by histopathological examination. Such diagnostic dilemmas are common in the infection caused by Cladophialophora, which can cause treatment delay and death. Early diagnosis is therefore mandatory for the rapid treatment and survival of patients 13).

2016

Kuan et al. report comprehensive genomic analyses of C. bantiana isolated from the brain abscess of an immunocompetent man, the first reported case in Malaysia and Southeast Asia. The identity of the fungus was determined using combined morphological analysis and multilocus phylogeny. The draft genome sequence of a neurotrophic fungus, C. bantiana UM 956 was generated using Illumina sequencing technology to dissect its genetic fundamental and basic biology. The assembled 37.1 Mb genome encodes 12,155 putative coding genes, of which, 1.01% are predicted transposable elements. Its genomic features support its saprophytic lifestyle, renowned for its versatility in decomposing hemicellulose and pectin components. The C. bantiana UM 956 was also found to carry some important putative genes that engaged in pathogenicity, iron uptake and homeostasis as well as adaptation to various stresses to enable the organism to survive in hostile microenvironment. This wealth of resource will further catalyse more downstream functional studies to provide better understanding on how this fungus can be a successful and persistent pathogen in human 14).


A 76-year-old man was admitted with mild motor aphasia and underwent total excision of a mass in the left frontal lobe. With the postoperative diagnosis of brain abscess due to infection with dematiaceous fungi (C. bantiana) associated with hypogammaglobulinemia following gastrectomy, intravenous antifungal drugs including amphotericin B and fluconazole were administered. Regrowth of the abscess with intraventricular rupture was noted at about the 88th day after the initial surgery, and the patient underwent neuroendoscopic aspiration of the pus and placement of a ventricular drain. Following intraventricular administration of miconazole through ventricular drainage or an Ommaya reservoir, neuroradiological findings improved, but general and neurological conditions worsened. Further treatment was discontinued and the patient died 9 months after onset. The poor outcome in this patient is attributed to 1)intractability of dematiaceous fungi, 2)development of ventriculitis and the need for intraventricular administration of antifungal drugs, and 3)untreatable hypogammaglobulinemia following gastrectomy 15).

2014

A 34 year old immunocompetent woman who presented with convulsions. She was initially treated with antituberculous drug. During 15 days of treatment, she deteriorated. Hence she underwent craniotomy, which revealed brain abscesses due to C. bantiana. Subsequently she was treated with fluconazole , but eventually succumbed to the infection on the 7th day of treatment. Mortality remains high with this rare mycosis, even in immunocompetent patients. The case illustrates the clinical and radiological similarities between tuberculoma and other etiologies of brain abscesses. This emphasizes the need to perform histological and microbiological studies prior to the initiation of any form of therapy 16).


A 27 year-old male patient presenting without any chronic disease was admitted to the emergency department of our hospital with the complaints of persistent headache and diplopia. Magnetic resonance imaging (MRI) showed a space-occupying lesion in the right parietal lobe and left frontal lobe. Brain abscess was diagnosed in the patient who was referred to the neurosurgery department. Treatment was initiated with ceftriaxone and metronidazole. The abscess material sent for direct microscopic examination in the mycology laboratory was stained with Gram and Giemsa and cultured in the Sabouraud dextrose agar medium (SDA) with and without antibiotics (cycloheximide and chloramphenicol). Then, it was incubated at 37°C and 25°C. Direct examination and staining revealed a septate hyphae. The patient who received liposomal amphotericin B was referred to the infectious diseases department. Surface colors of all media including SDA with cycloheximide were olive-gray to black and contained velvety colonies. Lemon-like very long and integrated chains of conidium with poor branching in cornmeal Tween 80 agar, as well as growth at 42°C in passages, positive urease test result and cycloheximide resistance suggested C.bantiana. The isolate was confirmed as C. bantiana based on its DNA sequence analysis. Minimum inhibitor concentration (MIC) values for amphotericin B, voriconazole, caspofungin, and posaconazole were 2 µg/ml, 0.03 µg/ml, 0.03 µg/ml and 0.03 µg/ml, respectively. Liposomal amphotericin B was replaced with voriconazole due to the antifungal susceptibility profile. The patient who was symptom-free was discharged at 24 days after hospitalization with oral voriconazole treatment. In conclusion, cerebral phaeohyphomycosis should be considered in immunocompetent individuals. Given the fact that early diagnosis saves lives, such specimens should promptly be sent for mycological analysis 17).


A case of multiple brain abscesses caused by C. bantiana in an immune competent patient. The diagnosis was based on CT scan of head, direct examination and culture of the aspirate from the abscess. Despite complete surgical resection of the abscesses and antifungal therapy with amphotericin B and voriconazole the patient could not be saved. All the cases of cerebral phaeohyphomycosis due to this rare neurotropic fungus reported from India between 1962 and 2009 have also been reviewed 18).

2008

A 20-yr-old male presented with multiple brain abscess which was subsequently proven microbiologically to be due to Cladophialophora Bantiana. In spite of near total excision and appropriate antifungal agents succumbed to his illness.

George et al. report this case to highlight its rarity and high mortality in an immunocompetent host. There is no initial clinical or laboratory feature that makes a preoperative diagnosis possible and relies on microbiological confirmation 19).


A 53-year-old male who presented with headache, tremor and memory disturbance. Radiological evaluation was suggestive of brain abscess. He underwent gross total excision of the cerebral abscess. The histopathological examination and pus culture was suggestive of brain abscess caused by Cladophialophora bantiana. Authors report a rare case of biopsy and culture proven Cladophialophora bantiana brain abscess in an immunocompetent host. The authors review the relevant literature and current treatment options while emphasizing the need for a cost-effective novel antifungal drug to salvage a subset of patients suffering from this rare but increasingly frequent condition 20).

2006

Cerebral phaeiohyphomycosis due to Cladophialophora bantiana 21).

2005

Lyons et al.report the first successfully treated case of Cladophialophora bantiana cerebral abscess with the relatively new antifungal agent voriconazole. Infection with this organism is often fatal. A 64-year-old man presented to our institution with progressive neurologic symptoms due to a brain abscess. A stereotactic brain biopsy confirmed the pathogen as C. bantiana. We discuss the successful treatment of this patient, and review the pharmacological actions of voriconazole and the literature on the treatment of this organism. Previously considered a rare cause of cerebral abscess, C. bantiana fungal infections have become more common in recent years. Aggressive and continuous treatment with voriconazole may offer an improved chance of survival in these patients 22).

References

1) , 14)

Kuan CS, Cham CY, Singh G, Yew SM, Tan YC, Chong PS, Toh YF, Atiya N, Na SL, Lee KW, Hoh CC, Yee WY, Ng KP. Genomic Analyses of Cladophialophora bantiana, a Major Cause of Cerebral Phaeohyphomycosis Provides Insight into Its Lifestyle, Virulence and Adaption in Host. PLoS One. 2016 Aug 29;11(8):e0161008. doi: 10.1371/journal.pone.0161008. eCollection 2016. PubMed PMID: 27570972; PubMed Central PMCID: PMC5003357.

2) , 17)

Atalay MA, Koç AN, Koyuncu S, Ulu Kiliç A, Kurtsoy A, Alp Meşe E. [Cladophilaphora bantiana brain abscess treated with voriconazole in an immunocompetent patient]. Mikrobiyol Bul. 2014 Jul;48(3):501-6. Turkish. PubMed PMID: 25052118.

3)

Menon S, Bharadwaj R, Chowdhary A, Kaundinya DV, Palande DA. Current epidemiology of intracranial abscesses: a prospective 5 year study. J Med Microbiol. 2008 Oct;57(Pt 10):1259-68. doi: 10.1099/jmm.0.47814-0. PubMed PMID: 18809555.

4) , 19)

George IA, Mathews MS, Karthik R, John L, Sundar A, Abraham OC, Joseph V. Fatal cerebral abscess caused by Cladophialophora bantiana. J Assoc Physicians India. 2008 Jun;56:470-2. PubMed PMID: 18822631.

5) , 7) , 11)

Ahmad M, Jacobs D, Wu HH, Wolk DM, Kazmi SAJ, Jaramillo C, Toms SA. Cladophialophora Bantiana : A Rare Intracerebral Fungal Abscess-Case Series and Review of Literature. Surg J (N Y). 2017 Mar 30;3(2):e62-e68. doi: 10.1055/s-0037-1598248. eCollection 2017 Apr. PubMed PMID: 28825023; PubMed Central PMCID: PMC5553499.

6)

Al-Abdely HM, Najvar LK, Bocanegra R, Graybill JR. Antifungal therapy of experimental cerebral phaeohyphomycosis due to Cladophialophora bantiana. Antimicrob Agents Chemother. 2005 May;49(5):1701-7. PubMed PMID: 15855484; PubMed Central PMCID: PMC1087650.

8) , 12)

Garg N, Devi IB, Vajramani GV, Nagarathna S, Sampath S, Chandramouli BA, Chandramuki A, Shankar SK. Central nervous system cladosporiosis: an account of ten culture-proven cases. Neurol India. 2007 Jul-Sep;55(3):282-8. PubMed PMID: 17921658.

9)

Dash C, Kumar A, Doddamani RS. Is complete excision the key to cure for Cladophialophora bantiana brain abscess? A review of literature. Neurol India. 2016 Sep-Oct;64(5):1062-4. doi: 10.4103/0028-3886.190250. PubMed PMID: 27625264.

10)

Chakrabarti A, Kaur H, Rudramurthy SM, Appannanavar SB, Patel A, Mukherjee KK, Ghosh A, Ray U. Brain abscess due to Cladophialophora bantiana: a review of 124 cases. Med Mycol. 2016 Feb;54(2):111-9. doi: 10.1093/mmy/myv091. Epub 2015 Oct 18. Review. PubMed PMID: 26483430.

13)

Lahiri Mukhopadhyay S, Mahadevan A, Bahubali VH, Dawn Bharath R, Prabhuraj AR, Maji S, Siddaiah N. A rare case of multiple brain abscess and probably disseminated phaeohyphomycosis due to Cladophialophora bantiana in an immunosuppressed individual from India. J Mycol Med. 2017 May 3. pii: S1156-5233(16)30233-5. doi: 10.1016/j.mycmed.2017.04.002. [Epub ahead of print] PubMed PMID: 28478966.

15)

Shimogawa T, Sayama T, Haga S, Akiyama T, Makihara K, Morioka T. [Brain Abscess due to Infection with Dematiaceous Fungi Cladophialophora bantiana Associated with Hypogammaglobulinemia Following Gastrectomy: A Case Report]. No Shinkei Geka. 2016 Jan;44(1):59-66. doi: 10.11477/mf.1436203208. Japanese. PubMed PMID: 26771098.

16)

Khetan SP, Agrawal VA, Qazi MS. Cerebral phaeohyphomycosis–could early diagnosis have saved the patient? Indian J Med Microbiol. 2014 Oct-Dec;32(4):440-2. doi: 10.4103/0255-0857.142248. PubMed PMID: 25297034.

18)

Suri P, Chhina DK, Kaushal V, Kaushal RK, Singh J. Cerebral Phaeohyphomycosis due to Cladophialophora bantiana – A Case Report and Review of Literature from India. J Clin Diagn Res. 2014 Apr;8(4):DD01-5. doi: 10.7860/JCDR/2014/7444.4216. Epub 2014 Apr 15. PubMed PMID: 24959445; PubMed Central PMCID: PMC4064842.

20)

Borkar SA, Sharma MS, Rajpal G, Jain M, Xess I, Sharma BS. Brain abscess caused by Cladophialophora Bantiana in an immunocompetent host: need for a novel cost-effective antifungal agent. Indian J Med Microbiol. 2008 Jul-Sep;26(3):271-4. Review. PubMed PMID: 18695333.

21)

Pardo F, Ferrer E, Romero PA, Pérez del Molino ML. Cerebral phaeiohyphomycosis due to Cladophialophora bantiana. Enferm Infecc Microbiol Clin. 2006 Nov;24(9):593-4. PubMed PMID: 17125684.

22)

Lyons MK, Blair JE, Leslie KO. Successful treatment with voriconazole of fungal cerebral abscess due to Cladophialophora bantiana. Clin Neurol Neurosurg. 2005 Oct;107(6):532-4. Epub 2005 Jan 13. PubMed PMID: 16202830.

Update: Spinal intramedullary tuberculosis

Spinal intramedullary tuberculosis

First reported by Cascino and Dibble 1).

Epidemiology

Intramedullary spinal tuberculosis is rare and constitute only 0.2-5% of all CNS tuberculoma2) 3). The combination of intramedullary and intracranial tuberculomas is extremely rare and only few cases have been reported in the literature so far 4) 5) 6) 7) 8).

Clinical features

Clinical presentation of spinal intramedullary tuberculosis (SIMT) is similar to intramedullary spinal cord tumor, with a characteristic subacute myelopathy, with slowly progressive paraplegia, sensory deficits, and/or bowel and bladder dysfunction.

Diagnosis

Diagnosis is strongly suspected with a clinical history of known tuberculosis in conjunction with characteristic findings on magnetic resonance imaging.

The MRI is a sensitive and non-invasive tool for diagnosing and localizing intramedullary as well as brain tuberculomas. The lesion appears as an isointense or hyperintense ring on the T1-weighted images and as an isointense or hypointense lesion on the T2-weighted images. MRI will also delineate the extent of surrounding edema. MRI also helps in determining the stage of tuberculoma formation. Presence of a bright central spot in the granuloma (target sign) is indicative of central caseation (rich foci).

Gd-DTPA enhancement MRI is more sensitive than MRI without enhancement in demonstrating the lesions of tuberculoma and arachnoiditis. In early stages of brain tuberculoma contrast MRI will show homogeneous enhancement representing the early tuberculoma stage, which may later evolve to ring enhancement with hypointense center. 9) 10) 11).

Jaiswal et al. suggest that MRI of the brain should be performed in all case of intramedullary spinal tuberculoma because of the possible presence of early asymptomatic/mild symptomatic intracranial tuberculomas 12).

Treatment

Management involves multiagent antitubercular chemotherapy without or with operative intervention.

Conservative treatment with antituberculosis medications and a short course of injectable steroids offers an effective, inexpensive, safe, and feasible option for treating intra-medullary tuberculoma, especially in developing countries 13).

Role of steroid is largely unproven. However, in patients with peri-lesional edema short-term steroids may be helpful 14). Usually, the conservative treatment is successful in achieving complete clinical neurological recovery over a period of 1 year, which is also accompanied by resolution of the tuberculomas 15).

Surgery is reserved for the patients with large lesions causing significant compression, patients who do not respond to or deteriorates during conservative treatment 16) 17) 18) 19) 20) 21) 22) 23) 24).

Case series

2009

Fifteen patients were analyzed. Mean age of presentation was 31 years (range: 18-45 years), with average duration at presentation being 11 months (2-24 months). Common locations: dorsal region: 7 cases, cervical: 5 cases, cervicodorsal: 2 cases and dorsolumbar region: 1 case. Sensori-motor involvement was noted in fourteen patients. Bowel and bladder involvement was seen in ten patients while one patient had respiratory distress. Only 40% of patients had secondary involvement of spine while the rest of the cases were having primary spinal intramedullary tuberculosis. Three patients had previous history of tubercular meningitis, while one patient had old pulmonary tuberculosis. There were one case each of cervical node involvement and intracranial granuloma. Twelve patients underwent surgery while others were conservatively managed, all patients received antitubercular therapy for 18 months. Nine of the twelve operated patients showed improvement in motor power, while two of the conservatively managed patients improved. Patients presenting late had a poorer outcome.

Spinal intramedullary tuberculosis is a non-malignant, treatable lesion giving a good outcome on management. Surgically managed patients showed a better outcome 25).

2002

During a period of 16 years (1985-2000), ten cases of intramedullary tuberculomas were diagnosed in All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India. Of these, eight cases were histologically proven intramedullary tuberculomas. The clinical profile, radiological data and histological slides were reviewed.

Age ranged from 18 to 45 years (mean 29.7 years) and there was slight male preponderance (six men, four women). Duration of symptom varied from 3 to 20 months (mean 11.5 months). All of them presented with motor weakness and sensory impairment. Most common site of involvement was dorsal cord followed by cervical, cervicodorsal and dorsolumbar regions. Three patients had associated involvement of lungs, cervical lymphnodes, and brain, and one patient had past history of tuberculous meningitis. Two patients were treated conservatively but surgical excision was done in eight cases followed by medical treatment.

Radiologically, intramedullary tuberculomas should be differentiated from other space occupying lesions (SOL) to avoid unnecessary surgery especially in those patients with tuberculosis of the other organs. The incidence of intramedullary tuberculomas is likely to increase with a rise in the incidence of AIDS 26).

Case reports

2017

A case of concurrent occurrence of intramedullary tuberculoma with multiple intracranial tuberculomas in a young 16-year-old boy, who presented with two weeks history of paresthesias and weakness of the lower limbs and diminution of vision in left eye, who had been treated for pulmonary tuberculosis. Magnetic resonance imaging (MRI) spine showed a well-circumscribed lesion opposite L1, which was diagnosed as intramedullary tuberculoma. As for vision complaint, on cranial imaging, he was found to have multiple round contrast enhancing lesions, which were diagnosed as intracranial tuberculomas based on their typical MRI findings. He had complete recovery with conventional treatment of anti-tubercular therapy and steroids, without any surgical intervention.

They suggest that MRI of the brain should be performed in all case of intramedullary spinal tuberculoma because of the possible presence of early asymptomatic/mild symptomatic intracranial tuberculomas 27).


A 9 month old boy with a retrospectively-recognized history of pulmonary TB presenting with fever and back tenderness found to have lower extremity hypertonia and clonus. Imaging revealed concurrent intracranial and spinal intramedullary tuberculomas. The patient was treated for hydrocephalus with external ventricular drainage followed by T8-10 laminectomy, drainage of abscess, and duraplasty. Parietal lobe biopsies proved the tuberculous etiology of intracranial lesions 28).


Varghese et al. report the case of a 49-year-old female with dull aching pain of both upper limbs of 1-week duration. On examination, she had no motor deficits. All the deep tendon reflexes were normal. The plantar responses were flexor bilaterally. Cervical spine imaging favored intramedullary tumor. She had partial relief of symptoms with steroid treatment. Repeat imaging done 1 month later revealed mild interval enlargement of the intramedullary lesions and multiple enlarged mediastinal and hilar nodes. Endoscopic ultrasound-guided fine-needle aspiration cytology of mediastinal nodes was suggestive of granulomatous inflammation. Hence, SIMT was considered as the probable diagnosis. The patient was started on antituberculosis therapy 29).

2015

A 25-year-old male who presented with a history of progressive paraparesis. Initial diagnosis was made as an intramedullary tumor by magnetic resonance imaging (MRI). The treatment of the patient involved is complete surgical excision of intramedullary lesion followed by appropriate antituberculous therapy. Postoperatively, his neurological symptoms were dramatically improved. With combination of both surgical and medical treatments, excellent clinical outcome was obtained.

This case illustrates the risk of misdiagnosis and the importance of histological confirmation of a pathological lesion as spinal cord tuberculoma prior to surgical therapy, which should be kept in mind as a differential diagnosis of the intramedullary spinal cord tumors 30).

2012

A patient with dorsal intramedullary tuberculoma who improved clinically as well as radiologically with antituberculous treatment and steroids 31).

References

1)

Cascino J, Dibble JB. Tuberculoma of spinal cord. JAMA. 1956;162(5):461–462.
2) , 16)

Citow JS, Ammirati M. Intramedullary tuberculoma of the spinal cord: Case report. Neurosurgery. 1994;35:327–30.
3) , 17)

Süzer T, Coşkun E, Tahta K, Bayramoǧlu H, Düzcan E. Intramedullary spinal tuberculoma presenting as a conus tumor: A case report and review of the literature. Eur Spine J. 1998;7:168–71.
4) , 14)

Huang CR, Lui CC, Chang WN, Wu HS, Chen HJ. Neuroimages of disseminated neurotuberculosis: Report of one case. Clin Imaging. 1999;23:218–22.
5) , 9)

Lin SK, Wu T, Wai YY. Intramedullary spinal tuberculomas during treatment of tuberculous meningitis. Clin Neurol Neurosurg. 1994;96:71–8.
6) , 18)

Shen WC, Cheng TY, Lee SK, Ho YJ, Lee KR. Disseminated tuberculomas in spinal cord and brain demonstrated by MRI with gadolinium-DTPA. Neuroradiology. 1993;35:213–5.
7) , 10) , 13) , 15)

Thacker MM, Puri AI. Concurrent intra-medullary and intra-cranial tuberculomas. J Postgrad Med. 2004;50:107–9.
8) , 19)

Yen HL, Lee RJ, Lin JW, Chen HJ. Multiple tuberculomas in the brain and spinal cord: A case report. Spine (Phila Pa 1976) 2003;28:E499–502.
11) , 20)

Shaharao VB, Pawar M, Agarwal R, Bavdekar SB. Intra-medullary tuberculoma occurring during treatment of tuberculous meningitis. Indian J Pediatr. 2004;71:107–8.
12) , 27)

Jaiswal M, Gandhi A, Purohit D, Mittal RS. Concurrent multiple intracranial and intramedullary conus tuberculoma: A rare case report. Asian J Neurosurg. 2017 Apr-Jun;12(2):331-333. doi: 10.4103/1793-5482.143461. PubMed PMID: 28484568; PubMed Central PMCID: PMC5409404.
21)

Gupta VK, Sharma BS, Khosla VK. Intramedullary tuberculoma: Report of two cases with MRI findings. Surg Neurol. 1995;44:241–3.
22)

Kayaoglu CR, Tuzun Y, Boga Z, Erdogan F, Gorguner M, Aydin IH. Intramedullary spinal tuberculoma: A case report. Spine (Phila Pa 1976) 2000;25:2265–8.
23)

Kumar R, Jain R, Kaur A, Chhabra DK. Brain stem tuberculosis in children. Br J Neurosurg. 2000;14:356–61.
24)

Rhoton EL, Ballinger WE, Jr, Quisling R, Sypert GW. Intramedullary spinal tuberculoma. Neurosurgery. 1988;22:733–6
25)

Ramdurg SR, Gupta DK, Suri A, Sharma BS, Mahapatra AK. Spinal intramedullary tuberculosis: a series of 15 cases. Clin Neurol Neurosurg. 2009 Feb;111(2):115-8. doi: 10.1016/j.clineuro.2008.09.029. Epub 2008 Dec 5. PubMed PMID: 19058910.
26)

Sharma MC, Arora R, Deol PS, Mahapatra AK, Sinha AK, Sarkar C. Intramedullary tuberculoma of the spinal cord: a series of 10 cases. Clin Neurol Neurosurg. 2002 Sep;104(4):279-84. PubMed PMID: 12140088.
28)

Ghali MGZ, Srinivasan VM, Kim CJ, Malik A. Spinal intramedullary tuberculosis with concurrent supra- and infratentorial intracranial disease in a 9 month old boy: case report and review of the literature. World Neurosurg. 2017 May 19. pii: S1878-8750(17)30768-4. doi: 10.1016/j.wneu.2017.05.069. [Epub ahead of print] Review. PubMed PMID: 28532916.
29)

Varghese P, Abdul Jalal MJ, Kandathil JC, Mathew IL. Spinal Intramedullary Tuberculosis. Surg J (N Y). 2017 Mar 30;3(2):e53-e57. doi: 10.1055/s-0037-1599823. eCollection 2017 Apr. PubMed PMID: 28825021; PubMed Central PMCID: PMC5553513.
30)

Mishra SS, Das D, Das S, Mohanta I, Tripathy SR. Spinal cord compression due to primary intramedullary tuberculoma of the spinal cord presenting as paraplegia: A case report and literature review. Surg Neurol Int. 2015 Mar 23;6:42. doi: 10.4103/2152-7806.153844. eCollection 2015. PubMed PMID: 25883834; PubMed Central PMCID: PMC4392528.
31)

Thirunavukarasu SC, Ramachandrappa A. A rare case of intramedullary tuberculoma: Complete resolution after medical treatment and role of magnetic resonance imaging in diagnosis and follow-up. Asian J Neurosurg. 2012 Oct;7(4):223-6. doi: 10.4103/1793-5482.106661. PubMed PMID: 23559994; PubMed Central PMCID: PMC3613649.

Update: Cryptococcal meningitis

Cryptococcal meningitis

Cryptococcosis is a fungal infection caused by Cryptococcus spp. that enters the body via inhalation, which mainly invades the lungs and central nervous system.

Two types of fungus can cause cryptococcal meningitis (CM). They are called Cryptococcus neoformans (C. neoformans) and Cryptococcus gattii (C.gattii). This disease is rare in healthy people. CM is more common in people who have compromised immune systems, such as people who have AIDS.

Cryptococcal meningitis may have long-term morbidity and requires a permanent cerebrospinal fluid shunt.

see Cryptococcus neoformans ventriculoperitoneal shunt infection.

see Cryptococcal choroid plexitis.

Clinical features

Cryptococcal meningitis are usually subacute or chronic in nature. HIV-infected patients may have minimal or nonspecific symptoms. Common symptoms are as follows:

Headache

Confusion

Lethargy

Obtundation

Coma

Normal or mildly elevated temperature

Nausea and vomiting (with increased intracranial pressure)

Fever and stiff neck (with an aggressive inflammatory response; less common)

Blurred vision, photophobia, and diplopia

Hearing defects, seizures, ataxia, aphasia, and choreoathetoid movements

After lung and CNS infection, the next most commonly involved organs in disseminated cryptococcosis include the skin, the prostate, and the medullary cavity of bones. Cutaneous manifestations (10-15% of cases) are as follows:

Papules, pustules, nodules, ulcers, or draining sinuses

Umbilicated papules in patients with AIDS

Cellulitis with necrotizing vasculitis in organ transplant recipients

Other less common forms of cryptococcosis include the following:

Optic neuritis or endophthalmitis

Myocarditis

Chorioretinitis

Hepatitis

Peritonitis

Renal abscess

Myositis

Adrenal involvement.

Diagnosis

The workup in patients with suspected cryptococcosis includes the following:

Cutaneous lesions: Biopsy with fungal stains and cultures

Blood: Fungal culture, cryptococcal serology, and cryptococcal antigen testing

Cerebrospinal fluid: India ink smear, fungal culture, and cryptococcal antigen testing

Urine and sputum cultures, even if renal or pulmonary disease is not clinically evident

In AIDS patients with cryptococcal pneumonia, culture of bronchoalveolar lavage washings

With possible CNS cryptococcosis, especially in patients who present with focal neurologic deficits or a history compatible with slowly progressive meningitis, consider obtaining a computed tomography or magnetic resonance imaging scan of the brain prior to performing a lumbar puncture. If a mass lesion is identified, do not perform a lumbar puncture to obtain spinal fluid; rather, consult a neurosurgeon for an alternative procedure.

With pulmonary cryptococcosis, radiographic findings in patients who are asymptomatic and immunocompetent may include the following:

Patchy pneumonitis

Granulomas ranging from 2-7 cm

Miliary disease similar to that in tuberculosis.

Treatment

Treatment of cryptococcal meningitis consists of three phases: induction, consolidation, and maintenance. Effective induction therapy requires potent fungicidal drugs (amphotericin B and flucytosine), which are often unavailable in low-resource, high-endemicity settings. As a consequence, mortality is unacceptably high. Wider access to effective treatment is urgently required to improve outcomes. For human immunodeficiency virus-infected patients, judicious management of asymptomatic cryptococcal antigenemia and appropriately timed introduction of antiretroviral therapy are important 1).

Case series

2017

A study aimed to evaluate the risk factors and create a predictive model for permanent shunt treatment in cryptococcal meningitis patients. This was a retrospective analytical study conducted at Khon Kaen University. The study period was from January 2005 to December 2015.

They enrolled all adult patients diagnosed with cryptococcal meningitis. Risk factors predictive for permanent shunting treatment were analyzed by multivariate logistic regression analysis. There were 341 patients diagnosed with cryptococcal meningitis. Of those, 64 patients (18.7%) were treated with permanent shunts. There were three independent factors associated with permanent shunt treatment. The presence of hydrocephalus had the highest adjusted OR at 56.77. The resulting predictive model for permanent shunt treatment (y) is (-3.85) + (4.04 × hydrocephalus) + (2.13 × initial CSF opening pressure (OP) > 25 cm H2O) + (1.87 × non-HIV). In conclusion, non-HIV status, initial CSF OP greater than or equal to 25 cm H2O, and the presence of hydrocephalus are indicators of the future necessity for permanent shunt therapy 2).

2014

In Japan, most cases of cryptococcosis are caused by Cryptococcus neoformans(C. neoformans). Until now, only three cases which the infectious agent was Cryptococcus neoformans var. gattii(C. gattii)have been reported. As compared with cryptococcosis caused by C. neoformans, which is often observed in immunocompromised hosts, cryptococcosis caused by C. gattii occurs predominantly in immunocompetent hosts and is resistant to antifungal drugs. Here, we report a case of refractory cerebral cryptococcoma that was successfully treated by surgical resection of the lesions. A 33-year-old man with no medical history complained of headache, hearing disturbance, and irritability. Pulmonary CT showed a nodular lesion in the left lung. Cerebrospinal fluid examination with Indian ink indicated cryptococcal meningitis, and PCR confirmed infection with C. gattii. C. gattii is usually seen in the tropics and subtropics. Since this patient imported trees and soils from abroad to feed stag beetles, parasite or fungal infection was, as such, suspected. Although he received 2 years of intravenous and intraventricular antifungal treatment, brain cryptococcomas were formed and gradually increased. Because of the refractory clinical course, the patient underwent surgical resection of the cerebral lesions. With continuation of antifungal drugs for 6 months after the surgeries, Cryptococcus could not be cultured from cerebrospinal fluid, and no lesions were seen on MR images. If cerebral cryptococcosis responds poorly to antifungal agents, surgical treatment of the cerebral lesion should be considered. 3).

1)

Sloan DJ, Parris V. Cryptococcal meningitis: epidemiology and therapeutic options. Clin Epidemiol. 2014 May 13;6:169-82. doi: 10.2147/CLEP.S38850. eCollection 2014. Review. PubMed PMID: 24872723; PubMed Central PMCID: PMC4026566.

2)

Phusoongnern W, Anunnatsiri S, Sawanyawisuth K, Kitkhuandee A. Predictive Model for Permanent Shunting in Cryptococcal meningitis. Am J Trop Med Hyg. 2017 Aug 14. doi: 10.4269/ajtmh.17-0177. [Epub ahead of print] PubMed PMID: 28820702.

3)

Inada T, Imamura H, Kawamoto M, Sekiya H, Imai Y, Tani S, Adachi H, Ishikawa T, Mineharu Y, Asai K, Ikeda H, Ogura T, Shibata T, Beppu M, Agawa Y, Shimizu K, Sakai N, Kikuchi H. [Cryptococcus Neoformans Var. Gattii meningoencephalitis with cryptococcoma in an immunocompetent patient successfully treated by surgical resection]. No Shinkei Geka. 2014 Feb;42(2):123-7. Japanese. PubMed PMID: 24501185.

SFTS virus and neurosurgery

The SFTS virus is a tick borne phlebovirus in the family Bunyaviridae. It appears to be more closely related to the Uukuniemi virus serogroup than to the Sandfly fever group.

It is a member of the Bhanja virus serocomplex.

The clinical condition it caused is known as severe fever with thrombocytopenia syndrome (SFTS).

SFTS is an emerging infectious disease that was first described in northeast and central China and now has also been discovered in Japan and South Korea. SFTS has a fatality rate of 12% and as high as 30% in some areas. The major clinical symptoms of SFTS are fever, vomiting, diarrhea, multiple organ failure, thrombocytopenia (low platelet count), leukopenia (low white blood cell count) and elevated liver enzyme levels.

Emergence of encephalitis/encephalopathy during severe fever with thrombocytopenia syndrome progression has been identified as a major risk factor associated with a poor prognosis.

Case reports

Yoo et al. report the first case of severe fever with thrombocytopenia syndrome (SFTS) and a acute spontaneous subdural hematoma (SDH) in Korea. A 79-year-old male presented with fever and thrombocytopenia. On the third day of hospitalization, his mental changed from drowsy to semi-coma. Brain computed tomography indicated an acute subdural hemorrhage on the right convexity. He was given early decompressive craniectomy, but did not survive. Real-time reverse transcription polymerase chain reaction analysis of a blood sample indicated the presence of SFTS virus (SFTSV). This is the first reported case with intracranial hemorrhage and SFTS. This case report describes our treatment of a patient with acute SDH and an infection from a tick-borne species of Bunyaviridae 1).


A 56-year-old Japanese man presented with fever and diarrhea, followed by dysarthria. Diffusion-weighted magnetic resonance imaging demonstrated high signal intensity in the splenium of the corpus callosum. The severe fever with thrombocytopenia syndrome virus genome was detected in our patient’s serum, and the clinical course was characterized by convulsion, stupor, and hemorrhagic manifestations, with disseminated intravascular coagulation and hemophagocytic lymphohistiocytosis. Supportive therapy not including administration of corticosteroids led to gradual improvement of the clinical and laboratory findings, and magnetic resonance imaging demonstrated resolution of the splenial lesion. The serum severe fever with thrombocytopenia syndrome viral copy number, which was determined with the quantitative reverse-transcription polymerase chain reaction, rapidly decreased despite the severe clinical course. The patient’s overall condition improved, allowing him to be eventually discharged.

Patients with encephalitis/encephalopathy due to severe fever with thrombocytopenia syndrome virus infection may have a favorable outcome, even if they exhibit splenial lesions and a severe clinical course; monitoring the serum viral load may be of value for prediction of outcome and potentially enables the avoidance of corticosteroids to intentionally cause opportunistic infection 2).

1)

Yoo J, Oh JW, Jang CG, Moon JH, Kim EH, Chang JH, Kim SH, Kang SG. Spontaneous Acute Subdural Hemorrhage in a Patient with a Tick Borne Bunyavirus-Induced Severe Fever with Thrombocytopenia Syndrome. Korean J Neurotrauma. 2017 Apr;13(1):57-60. doi: 10.13004/kjnt.2017.13.1.57. Epub 2017 Apr 30. PubMed PMID: 28512621; PubMed Central PMCID: PMC5432452.
2)

Kaneko M, Maruta M, Shikata H, Asou K, Shinomiya H, Suzuki T, Hasegawa H, Shimojima M, Saijo M. Unusual presentation of a severely ill patient having severe fever with thrombocytopenia syndrome: a case report. J Med Case Rep. 2017 Feb 3;11(1):27. doi: 10.1186/s13256-016-1192-0. PubMed PMID: 28153057; PubMed Central PMCID: PMC5290612.

Neurosurgery and ACS National Surgical Quality Improvement Program (ACS-NSQIP)


VP shunts were placed in 3,984 patients either as an initial placement (n = 1,093) or as a revision (n = 2,891). Compared to the initial-placement group, the revision group was significantly more likely to experience shunt failure (14 vs. 8%, p < 0.0001). In the initial-placement group, congenital hydrocephalus was independently associated with shunt failure (OR 1.83; 95% CI 1.01-3.31, p = 0.047). In the revision group, cardiac risk factors (OR 1.38; 95% CI 1.00-1.90, p = 0.047), a chronic history of seizures (OR 1.33; 95% CI 1.04-1.71, p = 0.022), and a history of neuromuscular disease (OR 0.61; 95% CI 0.41-0.90, p = 0.014) were independently associated with shunt failure.

Identifying the factors associated with VP shunt failure may allow the development of interventions to decrease failures. Further refinement of the collected variables in the ACS National Surgical Quality Improvement Program (NSQIP) Pediatric specific to neurosurgical procedures is necessary to identify modifiable risk factors 1).


Cote et al., performed a search of the ACS National Surgical Quality Improvement Program (ACS-NSQIP) database for all patients undergoing operations with a neurosurgeon from 2006 to 2013. They analyzed demographics, past medical history, and post-operative respiratory failure, defined as unplanned intubation and/or ventilator dependence for more than 48 h post-operatively.

Of 94,621 NSQIP-reported neurosurgical patients from 2006 to 2013, 2325 (2.5 %) developed post-operative respiratory failure. Of these patients, 1270 (54.6 %) were male, with an overall mean age of 60.59 years; 571 (24.56 %) were current smokers and 756 (32.52 %) were ventilator-dependent. Past medical history included dyspnea in 204 patients (8.8 %), COPD in 198 (8.5 %), and congestive heart failure in 66 (2.8 %). The rate of post-operative respiratory failure decreased from 4.1 % in 2006 to 2.1 % in 2013 (p < 0.001). Of the 2325 patients with respiratory failure, 1061 (45.6 %) underwent unplanned intubation post-operatively and 1900 (81.7 %) were ventilator-dependent for more than 48 h. The rate of both unplanned intubation (p < 0.001) and ventilator dependence (p < 0.001) decreased significantly from 2006 to 2013. Multivariate analysis demonstrated that significant risk factors for respiratory failure included inpatient status (p < 0.001, OR = 0.165), age (p < 0.001, OR = 1.014), diabetes (p = 0.001, OR = 1.489), functional dependence prior to surgery (p < 0.001, OR = 2.081), ventilator dependence (p < 0.001, OR = 10.304), hypertension requiring medication (p = 0.005, OR = 1.287), impaired sensorium (p < 0.001, OR = 2.054), CVA/stroke with or without neurological deficit (p < 0.001, OR = 2.662; p = 0.002, OR = 1.816), systemic sepsis (p < 0.001, OR = 1.916), prior operation within 30 days (p = 0.026, OR = 1.439), and operation type (cranial relative to spine, p < 0.001, OR = 4.344).

Based on the NSQIP database, risk factors for respiratory failure after neurosurgery include pre-operative ventilator dependence, alcohol use, functional dependence prior to surgery, stroke, and recent operation. The overall rate of respiratory failure decreased from 4.1 % in 2006 to 2.1 % in 2013 according to these data 2).


Data from adult patients who underwent surgery for spinal tumors (2011-2014) were extracted from the prospective National Surgical Quality Improvement Program (NSQIP) registry. Multivariable logistic regression was used to evaluate predictors of reoperation, readmission, and major complications (death, neurological, cardiopulmonary, venous thromboembolism [VTE], surgical site infection [SSI], and sepsis). Variables screened included patient age, sex, tumor location, American Society of Anesthesiologists (ASA) physical classification, preoperative functional status, comorbidities, preoperative laboratory values, case urgency, and operative time. Additional variables that were evaluated when analyzing readmission included complications during the surgical hospitalization, hospital length of stay (LOS), and discharge disposition.

Among the 2207 patients evaluated, 51.4% had extradural tumors, 36.4% had intradural extramedullary tumors, and 12.3% had intramedullary tumors. By spinal level, 20.7% were cervical lesions, 47.4% were thoracic lesions, 29.1% were lumbar lesions, and 2.8% were sacral lesions. Readmission occurred in 10.2% of patients at a median of 18 days (interquartile range [IQR] 12-23 days); the most common reasons for readmission were SSIs (23.7%), systemic infections (17.8%), VTE (12.7%), and CNS complications (11.9%). Predictors of readmission were comorbidities (dyspnea, hypertension, and anemia), disseminated cancer, preoperative steroid use, and an extended hospitalization. Reoperation occurred in 5.3% of patients at a median of 13 days (IQR 8-20 days) postoperatively and was associated with preoperative steroid use and ASA Class 4-5 designation. Major complications occurred in 14.4% of patients: the most common complications and their median time to occurrence were VTE (4.5%) at 9 days (IQR 4-19 days) postoperatively, SSIs (3.6%) at 18 days (IQR 14-25 days), and sepsis (2.9%) at 13 days (IQR 7-21 days). Predictors of major complications included dependent functional status, emergency case status, male sex, comorbidities (dyspnea, bleeding disorders, preoperative systemic inflammatory response syndrome, preoperative leukocytosis), and ASA Class 3-5 designation (p < 0.05). The median hospital LOS was 5 days (IQR 3-9 days), the 30-day mortality rate was 3.3%, and the median time to death was 20 days (IQR 12.5-26 days).

In a ACS National Surgical Quality Improvement Program analysis, 10.2% of patients undergoing surgery for spinal tumors were readmitted within 30 days, 5.3% underwent a reoperation, and 14.4% experienced a major complication. The most common complications were SSIs, systemic infections, and VTE, which often occurred late (after discharge from the surgical hospitalization). Patients were primarily readmitted for new complications that developed following discharge rather than exacerbation of complications from the surgical hospital stay. The strongest predictors of adverse events were comorbidities, preoperative steroid use, and higher ASA score. These models can be used by surgeons to risk-stratify patients preoperatively and identify those who may benefit from increased surveillance following hospital discharge 3).


Using the American College of Surgeons’ National Surgical Quality Improvement Program (ACS-NSQIP) dataset, a retrospective analysis of the complications experienced by patients that underwent surgical management of a UIA between the years of 2007 and 2013. The primary outcomes of interest were mortality within the 30-day perioperative period and adverse discharge disposition to a location other than home. Predictors of morbidity and mortality were elucidated using multivariable logistic regression analyses controlling for available patient demographic, comorbidity, and operative characteristics.

662 patients were identified in the ACS-NSQIP dataset for operative management of an unruptured aneurysm. The observed rates of 30-day mortality and adverse discharge disposition were 2.27% and 19.47%, respectively. A hundred and eight (16.31%) patients developed at least one major complication. On multivariable analysis, death within 30days was significantly associated with increased operative time (OR 1.005 per minute, 95% CI 1.002-1.008) and chronic preoperative corticosteroid use (OR 28.4, 95% CI 1.68-480.42), whereas major complication development was associated with increased operative time (OR 1.004 per minute, 95% CI 1.002-1.006), age (OR 1.017 per year, 95% CI 1-1.034), preoperative dependency (OR 3.3, 95% CI 1.16-9.40) and diabetes mellitus (OR 2.89, 95% CI 1.45-5.75). Lastly, increasing age (OR 1.017 per year, 95% CI 1-1.034) as well as ASA Class 3 (OR 1.73, 95% CI 1.08-2.77) and 4 (OR 2.28, 95% CI 1.1-4.72) were independent predictors of discharge to a location other than home.

The study yields morbidity and mortality benchmarks for UIA surgery in a representative, national surgical registry. It will hopefully aid in recognizing those patients at greater risk for postoperative complications following surgical management, leading to appropriate changes in treatment strategies for this selected group of patients 4).


2351 patients underwent peripheral nerve surgery, 120 complications were identified in 100 patients (4.25%), and 103 patients (4.38%) received nerve grafting. Thirty-one (1.95%) of the 1593 patients underwent unplanned readmission. Nerve grafting procedures had no association with postoperative complications and unplanned readmission rates. Patients who experienced an inpatient procedure (OR= 2.54, P<0.001), a longer operative time (OR= 1.00, P<0.001) and worse wound classifications (OR= 1.83, P<0.001) all had increased odds of postoperative complications. An inpatient procedure (OR= 2.74, P=0.014) and any complications (OR= 24.43, P<0.001) were significantly associated with unplanned readmission.

The study confirms that peripheral nerve surgery and nerve graft procedures can be safely performed with low complication risks and low unplanned readmission rates. We also identified the risks associated with perioperative adverse outcomes, and these data may be used as an adjunct for risk stratification for patients under consideration for peripheral nerve surgery. This approach may enable the improved targeting of the most costly and harmful complications of preventive measures 5).


1) Gonzalez DO, Mahida JB, Asti L, Ambeba EJ, Kenney B, Governale L, Deans KJ, Minneci PC. Predictors of Ventriculoperitoneal Shunt Failure in Children Undergoing Initial Placement or Revision. Pediatr Neurosurg. 2017;52(1):6-12. PubMed PMID: 27490129.
2) Cote DJ, Karhade AV, Burke WT, Larsen AM, Smith TR. Risk factors for post-operative respiratory failure among 94,621 neurosurgical patients from 2006 to 2013: a NSQIP analysis. Acta Neurochir (Wien). 2016 Sep;158(9):1639-45. doi: 10.1007/s00701-016-2871-8. Epub 2016 Jun 23. PubMed PMID: 27339268.
3) Karhade AV, Vasudeva VS, Dasenbrock HH, Lu Y, Gormley WB, Groff MW, Chi JH, Smith TR. Thirty-day readmission and reoperation after surgery for spinal tumors: a National Surgical Quality Improvement Program analysis. Neurosurg Focus. 2016 Aug;41(2):E5. doi: 10.3171/2016.5.FOCUS16168. PubMed PMID: 27476847.
4) Kerezoudis P, McCutcheon BA, Murphy M, Rayan T, Gilder H, Rinaldo L, Shepherd D, Maloney PR, Hirshman BR, Carter BS, Bydon M, Meyer F, Lanzino G. Predictors of 30-day perioperative morbidity and mortality of unruptured intracranial aneurysm surgery. Clin Neurol Neurosurg. 2016 Oct;149:75-80. doi: 10.1016/j.clineuro.2016.07.027. Epub 2016 Jul 27. PubMed PMID: 27490305.
5) Hu K, Zhang T, Hutter MM, Xu W, Williams ZM. Thirty-Day Perioperative Adverse Outcomes Following Peripheral Nerve Surgery: An Analysis of 2351 Patients in the ACS NSQIP Database. World Neurosurg. 2016 Jul 16. pii: S1878-8750(16)30545-9. doi: 10.1016/j.wneu.2016.07.023. [Epub ahead of print] PubMed PMID: 27436210.

Book: Cranial Osteomyelitis: Diagnosis and Treatment

Cranial Osteomyelitis: Diagnosis and Treatment
By Ali Akhaddar

Cranial Osteomyelitis: Diagnosis and Treatment

Price:$129.00 

ADD TO SHOPPING CART

This book is the first reference book covering exclusively all aspects of this challenging disease. It is designed to serve as a succinct appropriate resource for neurosurgeons, otorhinolaryngologists, neuroradiologists, researchers and infectious disease specialists with an interest in cranial infection. Cranial Osteomyelitis provides an in-depth review of knowledge of the management of skull osteomyelitis, with an emphasis on risk factors, causative pathogens, pathophysiology of dissemination, clinical presentations, neuroradiological findings and treatment modalities, medical and surgical. Sections on the prognosis and prevention of this illness are also included. The book will help the reader in choosing the most appropriate way to manage this challenging bone infection. In addition, it supplies clinicians and investigators with both basic and more sophisticated information and procedures relating to the complications associated with skull osteomyelitis. It also considers future areas of investigation and innovative therapeutic philosophies. The book is richly illustrated to provide readers with unparalleled access to a comprehensive collection of cranial osteomyelitis images (biological, clinical, neuroradiological, and surgical) taken directly from the author’s collection and experience in the field.


Product Details

  • Published on: 2016-04-24
  • Original language: English
  • Number of items: 1
  • Dimensions: 9.61″ h x .79″ w x 6.26″ l, .0 pounds
  • Binding: Hardcover
  • 325 pages

Ali AKHADDAR, MD, is Professor of Neurosurgery at the Faculty of Medicine, Mohammed V University in Rabat (Morocco) and Chairman of the Department of Neurosurgery at Avicenne Military Hospital of Marrakech (Morocco). He is an Expert Member of the Scientific Committees of the National Scientific and Technological Research Center of Morocco (CNRST). Dr Akhaddar is a Member of the American Association of Neurological Surgeons (AANS), the Congress of Neurological Surgeons (CNS), the French speaking society of Neurosurgery (SNCLF) and the Military Neurosurgeons Committee in the World Federation of Neurosurgical Societies (WFNS). He has received many awards during his career, including from the Moroccan Society of Neurosurgery, the World Federation of Neurosurgical Societies [Traveling Fellowship Award: Nagoya 2007, Boston 2009 and Seoul 2013], the University of Mohammed V of Rabat and the French Society of Hospitals’ History (SFHH).Dr Akhaddar is a member of the editorial board of the Open Neurosurgery Journal and Médecine du Maghreb and is a reviewing editor for many medical journals. He is the author of three previous books; he has authored and co-authored more than 200 papers published in peer-reviewed journals (140 indexed in PubMed*) and five book chapters.