Category Archives: Articles

Update: Double level isthmic spondylolisthesis

Double level isthmic spondylolisthesis

Isthmic spondylolisthesis, which is demonstrated in 4%-6% of the general population, is one of the most common types of spondylolisthesis. However, double-level isthmic spondylolisthesis is extremely rare. Only a few reports have examined the outcomes of surgical treatment of double-level spondylolisthesis.

Reviews

Between 2004 and 2014, thirty-two patients with double-level isthmic spondylolisthesis who underwent posterior lumbar interbody fusion (PLIF) with autogenous bone chips were reviewed retrospectively. The clinical outcomes were measured by VAS (Visual analog scale) and JOA(Japanese Orthopaedic Association) score.

At an average follow-up of 2.8 years, the mean score on the VAS of back pain and sciatica decreased from 6.48 and 4.26 points preoperatively to 1.82 and 1.10 points at final follow-up, respectively. The average JOA score improved from 13.8±3.1 preoperative to 25.6±1.3 (range, 17-28) points postoperative. The average recovery rate was 77.6%. The good and excellent rate was 84.3% (27/32). The fusion rate was 87.5% (28/32). Changes in disc height, degree of listhesis, whole lumbar lordosis, and sacral inclination between the pre- and postoperative periods were significant.

The findings suggest that PLIF with autogenous bone chips for double-level isthmic spondylolisthesis could yield good functional short-term results. It seems to be a viable approach in the treatment of double-level isthmic spondylolisthesis 1).

Case series

Fifty-four patients who were managed surgically for treatment of double-level symptomatic isthmic spondylolisthesis were included in this study. Between May 2004 and September 2012, 29 consecutive patients underwent posterior lumbar interbody fusion (PLIF) with autogenous bone chips (group I) at Foshan Hospital of Traditional Chinese Medicine, Guangdong, China. Between March 2005 and December 2013, 25 consecutive patients underwent PLIF with cage (group II) at Zhujiang Hospital of Southern Medical University, Guangdong, China. The mean follow-up periods were 27.2 and 26.8 months, respectively.

The mean VAS scores of back and leg pain significantly decreased from 7.2 to 2.2 and 5.8 to 2.1 in the group I and from 7.0 to 1.9 and 6.1 to 1.8 in the group II, respectively. In the group I, mean ODI scores improved significantly from 54% to 14.2% and, in the group II, from 60% to 12.6%. In both groups, VAS and ODI scores significantly changed from pre- to postoperatively (p<0.001), but postoperative outcome between groups was statistically not significant. Solid union was observed in 27 of 29 patients (89.6%) in the group I and in 22 of 25 patients (88%) in the group II, without statistically significant differences (p>0.05). In both groups, changes in disc height, degree of listhesis, and whole lumbar lordosis between the pre- and postoperative periods were significant.

Clinical and functional outcomes demonstrate no significant differences between groups in treating back and leg pain of adult patients with double-level isthmic spondylolisthesis 2).

Case reports

2017

To the best of Kim et al. knowledge, there has been no report regarding rheumatoid arthritis associated with spinal neuroarthropathy and combined double-level isthmic spondylolisthesis.

They report a rare case of spinal neuroarthropathy with double-level isthmic spondylolisthesis in a rheumatoid arthritis (RA) patient. A 56-year-old female patient under medical treatment for RA during the last 13 years presented aggravating radiating pain to her right lower extremity and a limping gait developed 4 months ago. The disease activity of RA had remained low for a long time. Serial radiographs during last 8-year follow-up showed progressive dislocation at L4-L5 and L5-S1 with double-level isthmic spondylolisthesis and severe destructive status at the last follow-up. The patient underwent decompression and circumferential fusion with sacropelvic fixation and acceptable reduction was obtained.

A RA patient with double-level isthmic spondylolisthesis showed a progressive destructive lesion. In addition to clinical presentations, the imaging findings were very similar to ones of spinal neuroarthropathy. The authors conclude that this Grand Round case probably had SNA secondary to RA and that this, combined with two-level isthmic spondylolisthesis, resulted in her rapidly progressing destructive lumbar lesion 3).

2014

Song et al. present an unusual case of double-level isthmic spondylolisthesis of the lumbar spine. The patient had low-back pain for 20 years and did not respond to conservative treatment. Radiographs revealed bilateral pars defects at L-4 and L-5. Grade 2 isthmic spondylolisthesis was present, both at L4-5 and at L5-S1. The patient underwent decompression, reduction, and posterior lumbar interbody fusion with autogenous bone chips from posterior decompression. At follow-up after 12 months, the patient was free of pain, slippage was corrected, and fusion was achieved. Posterior lumbar interbody fusion with posterior instrumentation and reduction may yield good functional short-term results for double-level spondylolisthesis 4).

2012

An unusual case of a double-level isthmic spondylolisthesis of the lumbar spine in a 38-year-old female was described. The patient had been suffering from low back pain for 8 years and did not respond to conservative treatment. Her medical examination revealed that grade II isthmic spondylolisthesis was present both at L-4 to L-5 and at L-5 to S-1. The patient was managed by surgical treatment. After the reduction of lysthesis with posterior instrumentation, posterior lumbar interbody fusion (PLIF) technique was performed for double level. At a recent follow-up, 1 year after the surgery, the symptoms of the patient were completely resolved, reduction was preserved, and fusion was achieved. PLIF with posterior instrumentation and reduction seems to be a convenient treatment option in the treatment for double-level spondylolisthesis 5).

1)

Song D, Song D, Zhang K, Chen Z, Wang F, Xuan T. Double-level isthmic spondylolisthesis treated with posterior lumbar interbody fusion: A review of 32 cases. Clin Neurol Neurosurg. 2017 Aug 19;161:35-40. doi: 10.1016/j.clineuro.2017.08.007. [Epub ahead of print] PubMed PMID: 28843115.
2)

Song D, Chen Z, Song D, Li Z. Comparison of posterior lumbar interbody fusion (PLIF) with autogenous bone chips and PLIF with cage for treatment of double-level isthmic spondylolisthesis. Clin Neurol Neurosurg. 2015 Nov;138:111-6. doi: 10.1016/j.clineuro.2015.08.012. Epub 2015 Aug 20. PubMed PMID: 26318362.
3)

Kim SI, Kim YH, Lee JW, Kang WW, Ha KY. Rheumatoid arthritis-associated spinal neuroarthropathy with double-level isthmic spondylolisthesis. Eur Spine J. 2017 Jul 28. doi: 10.1007/s00586-017-5220-6. [Epub ahead of print] PubMed PMID: 28755075.
4)

Song D, Chen Z, Song D. Surgical treatment of double-level isthmic spondylolisthesis. J Neurosurg Spine. 2014 Apr;20(4):396-9. doi: 10.3171/2013.12.SPINE13521. Epub 2014 Jan 31. PubMed PMID: 24484307.
5)

Uysal M, Circi E, Ozalay M, Derincek A, Cinar M. The surgical treatment for a rare case of double-level isthmic spondylolisthesis in L4 and L5 lumbar spine: decompression, reduction and fusion. Eur J Orthop Surg Traumatol. 2012 Nov;22 Suppl 1:21-4. doi: 10.1007/s00590-012-0993-0. Epub 2012 Apr 19. PubMed PMID: 26662742.

Update: Multinodular and vacuolating neuronal tumor of the cerebrum

Multinodular and vacuolating neuronal tumor of the cerebrum

Multinodular and vacuolating neuronal tumors of the cerebrum (MVNT) are superficial neuronal tumors in adults that were first documented in 2013 1)

It is a new pattern of neuronal tumour included in the World Health Organization Classification of Tumors of the Central Nervous System 2016, as a unique cytoarchitectural pattern of gangliocytoma.

There are fifteen reports in the literature to date. They are typically associated with late onset epilepsy.

Clinical, pathological and genetic data could indicate that MVNT aligns more with a malformative lesion than a true neoplasm with origin from a progenitor neuro-glial cell type showing aberrant maturation 2).

Differential diagnosis

Dysembryoplastic neuroepithelial tumor – DNET can appear similar but usually is mostly cortical (rather than subcortical) often has bright FLAIR rim focal cortical dysplasia (Type II) high T2 signal deep to cortex is in the same location but is usually associated with a radial glial band (transmantle sign) and with thickened abnormal overlying cortex perivascular spaces location can be similar usually more elongated along vessel long axis fully attenuating on FLAIR 3).

Treatment

MVNTs appear to be benign tumours with very indolent biological behaviour which can, if asymptomatic, be followed with imaging alone. In symptomatic patients (epileptic) surgical resection often controls seizures, with no tumour regrowth reported 4) 5) 6) 7).

Case series

2017

Thom et al. present a series of ten cases and compare their pathological and genetic features to better characterised epilepsy associated malformations including focal cortical dysplasia type II (FCDII) and low-grade epilepsy associated tumours (LEAT). Clinical and neuroradiology data were reviewed and a broad immunohistochemistry panel was applied to explore neuronal and glial differentiation, interneuronal populations, mTOR pathway activation and neurodegenerative changes. Next generation sequencing was performed for targeted multi-gene analysis to identify mutations common to epilepsy lesions including FCDII and LEAT. All of the surgical cases in this series presented with seizures, and were located in the temporal lobe. There was a lack of any progressive changes on serial pre-operative MRI and a mean age at surgery of 45 years. The vacuolated cells of the lesion expressed mature neuronal markers (neurofilament/SMI32, MAP2, synaptophysin). Prominent labelling of the lesional cells for developmentally regulated proteins (OTX1, TBR1, SOX2, MAP1b, CD34, GFAPδ) and oligodendroglial lineage markers (OLIG2, SMI94) was observed. No mutations were detected in the mTOR pathway genes, BRAF, FGFR1 or MYB. Clinical, pathological and genetic data could indicate that MVNT aligns more with a malformative lesion than a true neoplasm with origin from a progenitor neuro-glial cell type showing aberrant maturation 8).


Nunes et al. report 33 cases of presumed multinodular and vacuolating neuronal tumor of the cerebrum that exhibit a remarkably similar pattern of imaging findings consisting of a subcortical cluster of nodular lesions located on the inner surface of an otherwise normal-appearing cortex, principally within the deep cortical ribbon and superficial subcortical white matter, which is hyperintense on FLAIR. Only 4 of the cases are biopsy-proven because most were asymptomatic and incidentally discovered. The remaining were followed for a minimum of 24 months (mean, 3 years) without interval change. They demonstrate that these are benign, nonaggressive lesions that do not require biopsy in asymptomatic patients and behave more like a malformative process than a true neoplasm 9).

2013

Huse et al. report 10 cases of a non-neurocytic, purely neuronal tumor affecting adults. Situated in the cerebral hemispheres, with 7 of 10 confined to the temporal lobes, most presented with seizures as their principal clinical manifestations. On magnetic resosnance imaging (MRI), the tumors generally appeared solid and non-contrast enhancing with minimal diffuse infiltration, edema, or mass effect. Six examples demonstrated internal nodularity. Microscopically, the tumor cells were largely distributed into discrete and coalescent nodules exhibiting varying degrees of matrix vacuolization, principally within the deep cortical ribbon and superficial subcortical white matter. Populating elements ranged from morphologically ambiguous to recognizably neuronal, with only two cases manifesting overt ganglion cell cytology. In all cases, tumor cells exhibited widespread nuclear immunolabeling for the HuC/HuD neuronal antigens, although expression of other neuronal markers, including synaptophysin, neurofilament and chromogranin was variable to absent. Tumor cells also failed to express GFAP, p53, IDH1 R132H, or CD34, although CD34-labeling ramified neural elements were present in the adjoining cortex of seven cases. Molecular analysis in a subset of cases failed to reveal DNA copy number abnormalities or BRAF V600E mutation. Follow-up data indicate that this unusual neuronal lesion behaves in benign, World Health Organization (WHO) grade I fashion and is amenable to surgical control 10).

Case reports

2015

Fukushima et al. report a case of MNVT involving a 37-year-old man who presented with an epileptogenic, superficial solid lesion in the left parietal lobe. Histomorphology of the resected specimen was characterized by nodular lesions with vacuolation. Nodules comprised irregular proliferation of neuronal cells, which ranged from ganglion-like forms to those with indistinct lineage. Immunohistochemical analysis showed that the lesional cells stained positively for HuC/HuD, synaptophysin, and Olig2, and negatively for NeuN, neurofilament, chromogranin A, GFAP, CD34, IDH1(R132H), and BRAF(V600E). Eighteen months following surgery, the patient is well and without neurological deficits. MVNTs are distinctive tumors that should be differentiated from ganglion cell tumors, dysembryoplastic neuroepithelial tumors, and malformation of cortical development 11).

2014

Bodi et al. report the findings in two cases with similar features, a surgical resection and the other an autopsy specimen.Case 1, a 34-year-old female, underwent surgical resection for a multinodular non-enhancing frontal white matter lesion causing intractable epilepsy. Case 2, presented with motor neurone disease (MND) at the age of 71 and MRI scanning revealed extensive multinodular non-enhancing white matter lesions in the temporal lobe. There was no history of epilepsy and post mortem histology confirmed MND.Macroscopically multiple small grey well-formed, discrete and coalescent nodules were seen in the deep cortex and subcortical white matter. On histology, mature-looking neurons with large cytoplasmic vacuoles were distributed in a fibrillary background, where vacuoles were also noted. In the resected tumour scattered oligodendroglia-like cells were present. No ganglion cells were seen. The vacuolated cells exhibited immunopositivity for synaptophysin, HuC/HuD and p62 but were negative for NeuN, neurofilament, GFAP, IDH1, nestin and CD34. Electron microscopy showed non-membrane bound cytoplasmic vacuoles in the neurons and in some neuronal processes. The seizures recurred in Case 1.Some clinicopathological features of this lesion suggest a possible relationship with dysembryoplastic neuroepithelial tumour (DNT) although the morphological features are not typical of DNT. Case 2 demonstrates that MVNT may remain asymptomatic 12).

References

1) , 6) , 10)

Huse JT, Edgar M, Halliday J, Mikolaenko I, Lavi E, Rosenblum MK. Multinodular and vacuolating neuronal tumors of the cerebrum: 10 cases of a distinctive seizure-associated lesion. Brain Pathol. 2013 Sep;23(5):515-24. doi: 10.1111/bpa.12035. Epub 2013 Feb 1. PubMed PMID: 23324039.
2) , 8)

Thom M, Liu J, Bongaarts A, Reinten RJ, Paradiso B, Jäger HR, Reeves C, Somani A, An S, Marsdon D, McEvoy A, Miserocchi A, Thorne L, Newman F, Bucur S, Honavar M, Jacques T, Aronica E. MULTINODULAR AND VACUOLATING NEURONAL TUMOURS IN EPILEPSY: DYSPLASIA OR NEOPLASIA? Brain Pathol. 2017 Aug 19. doi: 10.1111/bpa.12555. [Epub ahead of print] PubMed PMID: 28833756.
4) , 12)

Bodi I, Curran O, Selway R, Elwes R, Burrone J, Laxton R, Al-Sarraj S, Honavar M. Two cases of multinodular and vacuolating neuronal tumour. Acta Neuropathol Commun. 2014 Jan 20;2:7. doi: 10.1186/2051-5960-2-7. PubMed PMID: 24444358; PubMed Central PMCID: PMC3899932.
5) , 11)

Fukushima S, Yoshida A, Narita Y, Arita H, Ohno M, Miyakita Y, Ichimura K, Shibui S. Multinodular and vacuolating neuronal tumor of the cerebrum. Brain Tumor Pathol. 2015 Apr;32(2):131-6. doi: 10.1007/s10014-014-0198-9. Epub 2014 Aug 22. PubMed PMID: 25146549.
7) , 9)

Nunes RH, Hsu CC, da Rocha AJ, do Amaral LLF, Godoy LFS, Watkins TW, Marussi VH, Warmuth-Metz M, Alves HC, Goncalves FG, Kleinschmidt-DeMasters BK, Osborn AG. Multinodular and Vacuolating Neuronal Tumor of the Cerebrum: A New “Leave Me Alone” Lesion with a Characteristic Imaging Pattern. AJNR Am J Neuroradiol. 2017 Jul 13. doi: 10.3174/ajnr.A5281. [Epub ahead of print] PubMed PMID: 28705817.

Update: Cystic metastases

Cystic metastases

Epidemiology

The development of cystic brain metastases remains a relatively rare occurrence.

Etiology

Metastatic brain tumors are normally composed of cystic components, however, the reasons for the cyst formation have not been clearly investigated 1). Stem 2) reported that the brain cyst fluid protein always presents in the inflammatory exudates. Cumings 3) also reported that the cyst fluid formation may be correlated with the tumor degeneration. Gardner et al 4) found that fluid accumulating in brain tumors runs in the normal drainage route, since there are no lymphatic vessels in the tumors.

Gamma knife radiosurgery (GKRS) is occasionally a useful tool for maintaining good brain status in patients with brain metastases (METs). Conversely, Ishikawa et al. experienced patients with delayed cyst formation (DCF) several years after GKRS, a complication not previously reported 5).

Differential diagnosis

The main challenge in discrimination between intracranial cystic lesions is to differentiate benign inflammatory cystic lesions (as cerebral abscess) from malignant cystic lesions (as cystic metastases and cystic glioma) which have totally different management.

Cerebral abscess.

Hydatid cyst.

Other intra-axial cysts, e.g. intracranial arachnoid cyst, neuroglial cyst, porencephalic cyst.

The most common tumors are, hemangioblastoma, pilocytic astrocytoma, ganglioglioma, pleomorphic xanthoastrocytoma, tanycytic ependymoma, intraparenchymal schwannoma, desmoplastic infantile ganglioglioma.

Cystic meningioma is a rare form of intracranial meningioma. Meningiomas are typically solid tumors but may rarely have cystic components. The diagnosis of cystic meningioma is clinically challenging as the finding of multiple intra-axial tumors, including metastatic tumors, is relatively common. We report a case of cystic meningioma initially diagnosed as a metastatic tumor from a recurrence of acute lymphoid leukemia. However, postoperative histopathological examination demonstrated an atypical meningioma 6).

Treatment

In a review, Kim et al. describe the characteristics of cystic brain metastasis and evaluate the combined use of stereotactic aspiration and radiosurgery in treating large cystic brain metastasis. The results of several studies show that stereotactic radiosurgery produces comparable local tumor control and survival rates as other surgery protocols. When the size of the tumor interferes with radiosurgery, stereotactic aspiration of the metastasis should be considered to reduce the target volume as well as decreasing the chance of radiation induced necrosis and providing symptomatic relief from mass effect. The combined use of stereotactic aspiration and radiosurgery has strong implications in improving patient outcomes 7).

Case series

2017

Between December 2007 and February 2015, 38 consecutive patients with 40 cystic metastases underwent Ommaya reservoir implantation at our institution. The patient characteristics, treatment parameters, and all available clinical and neuroimaging follow-ups were analyzed retrospectively.

The rate of volume reduction was significantly related to the location of the tube tip inside the cyst. By placing the tip at or near the center, 58.7% reduction was achieved, whereas reduction of 42.6% and 7.7% occurred with deep and shallow tip placement, respectively (p=0.011). Although there was no additional surgery in the center placement group, additional surgeries were performed in 5 out of the 23 deep and shallow cases due to inadequate volume reduction. No other factors were correlated with successful volume reduction.

For adequate volume reduction using the Ommaya reservoir in the treatment of cystic brain metastases prior to stereotactic radiosurgery, the tip of the reservoir tube should be placed at the center of the cyst 8).

2016

Lee et al. retrospectively reviewed the clinical, radiological, and dosimetry data of 37 cystic brain metastases of 28 patients who were treated with GKRS. Cyst drainage was performed in 8 large lesions before GKRS to decrease the target volume. The mean target volume was 4.8 (range, 0.3-15.8) cc at the time of GKRS, and the mean prescription dose was 16.6 (range, 13-22) Gy.

The actuarial median survival time was 17.7 ± 10.2 months, and the primary tumor status was a significant prognostic factor for survival. The actuarial local tumor control rate at 6 and 12 months was 93.1 and 82.3%, respectively. Among the various factors, only prescription dose (>15 Gy) was a significant factor related to local tumor control after multivariate analysis (p = 0.049). Cyst volume or cyst/total tumor volume ratio did not influence local control after GKRS, when the target volume was reduced to about 15 cc after cyst drainage.

According to this results, they suggest that stereotactic radiosurgery should be considered as one of the treatment options for cystic brain metastases, when large tumor volume can be reduced by surgical drainage before radiosurgery, especially for patients with a controlled primary tumor 9).


A study involved 48 patients who were diagnosed with cystic metastatic brain tumors between January 2008 and December 2012 in the Department of Neurosurgery of Nanfang Hospital Southern Medical University (Guangzhou, China). Every patient underwent Leksell stereotactic frame, 1.5T magnetic resonance imaging (MRI)-guided stereotactic cyst aspiration and Leksell GKRS. Subsequent to the therapy, MRI was performed every 3 months. The results indicated that 48 cases were followed up for 24-72 months, with a mean follow-up duration of 36.2 months. Following treatment, 44 patients (91.7%) exhibited tumor control and 4 patients (8.3%) experienced progression of the local tumor. During this period, 35 patients (72.9%) succumbed, but only 2 (4.2%) of these succumbed to the brain metastases. The total local control rate was 91.7% and the median overall survival time of all patients was 19.5 months. The 1-year overall survival rate was 70.8% and the 2-year overall survival rate was 26.2%. In conclusion, these results indicated that the method of stereotactic cyst aspiration combined with GKRS was safe and effective for patients with large cystic brain metastases. This method is effective for patients whose condition is too weak for general anesthesia and in whom the tumors are positioned at eloquent areas. This method enables patients to avoid a craniotomy, and provides a good tumor control rate, survival time and quality of life 10).

2014

Between February 2005 and March 2012, a total of 24 patients underwent GKR after cyst aspiration for 29 cystic metastatic brain tumors. The median age was 60 years (range, 18-81). The number of male patients was 18 and that of female patients 6. Most of the patients were in class II (87.5%) based on the data of the Radiation Therapy Oncology Group using recursive partitioning analysis. We analyzed the changes in tumor volume, the local control rate, intracranial progression-free survival (PFS) and overall survival (OS).

Before aspiration, the mean total tumor volume was 32.7 cm(3) (range, 12.1-103.3) and cystic volume was 18.6 cm(3) (range, 8-72.3). The mean duration of cyst drainage was 1 day (range, 1-2). The mean amount of aspiration was 16.8 cm(3) (range, 6-67.4). After aspiration, the total mean volume was 12.4 cm(3) (range, 3.7-38.1) and cystic volume was 2.0 cm(3) (range, 0.1-9.5). The nature of the cyst was serous in 18, serous and hemorrhagic in 3, and serous and necrotic in 8. The median prescription dose was 16 Gy (range, 14-20). There was no treatment-related complication. The local control rate was 58.6% (17/29). The median survival to local recurrence was 6.0 (±1.42) months. During the follow-up period, an Ommaya reservoir was placed in 3 patients. Insertion of an Ommaya reservoir and whole-brain radiotherapy (WBRT) or GKR were done in 2 patients, WBRT in 2, GKR in 1 and operation in 1. The median intracranial PFS and OS after intracranial metastasis was 5.2 (±0.42) and 6.8 (±0.38) months.

Cyst aspiration and GKR were feasible and safe but not very efficient, which could be an alternative option for large cystic metastases in patients who could not expect longer survival time 11).

2013

Ebinu et al. reviewed a prospectively maintained database of brain metastases patients treated between 2006 and 2010. All lesions with a cystic component were identified, and volumetric analysis was done to measure percentage of cystic volume on day of treatment and consecutive follow-up MRI scans. Clinical, radiologic, and dosimetry parameters were reviewed to establish the overall response of cystic metastases to GKRS as well as identify potential predictive factors of response.

A total of 111 lesions in 73 patients were analyzed; 57% of lesions received prior whole-brain radiation therapy (WBRT). Lung carcinoma was the primary cancer in 51% of patients, 10% breast, 10% colorectal, 4% melanoma, and 26% other. Fifty-seven percent of the patients were recursive partitioning analysis class 1, the remainder class 2. Mean target volume was 3.3 mL (range, 0.1-23 mL). Median prescription dose was 21 Gy (range, 15-24 Gy). Local control rates were 91%, 63%, and 37% at 6, 12, and 18 months, respectively. Local control was improved in lung primary and worse in patients with prior WBRT (univariate). Only lung primary predicted local control in multivariate analysis, whereas age and tumor volume did not. Lesions with a large cystic component did not show a poorer response compared with those with a small cystic component.

This study supports the use of GKRS in the management of nonsurgical cystic metastases, despite a traditionally perceived poorer response. Our local control rates are comparable to a matched cohort of noncystic brain metastases, and therefore the presence of a large cystic component should not deter the use of GKRS. Predictors of response included tumor subtype. Prior WBRT decreased effectiveness of SRS for local control rates 12).

2012

Between 2005 and 2010, 25 cystic metastases in 25 patients were treated at Dokkyo Medical University. The patients first underwent MRI and stereotactic aspiration of the cyst while stationary in a Leksell stereotactic frame; immediately afterward, the patients underwent a second MR imaging session and Gamma Knife treatment. Tumor volume reduction, tumor control rate, and overall survival were examined.

Tumor volume, including the cystic component, decreased from 8.0-64.2 cm(3) (mean 20.3 cm(3)) to 3.0-36.2 cm(3) (mean 10.3 cm(3)) following aspiration, and the volume of 24 of 25 lesions decreased to less than 16.6 cm(3), which is equivalent to the volume of a 3.16-cm sphere. At least 20 Gy was delivered to the entire lesion in 24 of 25 cases. Good tumor control was obtained in 16 of 21 cases that could be evaluated during a median follow-up period of 11 months (range 1-27 months); however, reaccumulation of cyst contents was observed in 2 patients who required Ommaya reservoir placement.

The 1-day aspiration plus GKS procedure is an effective and time-efficient treatment for large cystic brain metastases 13).

2009

Hydrofiber dressing is a sodium carboxymethylcellulose hydrocolloid polymer with high fluid-absorptive capacity. This material was originally used as a dressing for exudative wounds. Hydrofiber dressing was used for 8 patients with cystic-type metastatic brain tumor. Tumor removal was performed after hydrofiber dressing was inserted into the cyst cavity to transform the tumor into a solid-type tumor.

Transformation of cystic-type metastatic brain tumors into smaller solid-type tumors using hydrofiber dressing facilitated en bloc resection of tumor. The dressing also absorbed residual cyst fluid and was thus also effective in preventing intraoperative dissemination of tumor cells. This approach enabled ideal en bloc resection in all patients. There were no adverse events.

These findings suggest hydrofiber dressing may be useful in surgery for cystic-type metastatic brain tumors 14).

2008

Between January 2001 and November 2005, 680 consecutive patients with brain metastases underwent GKS at our hospital, 30 of whom were included in this study (18 males and 12 females, mean age 60.6 +/- 11 years, range 38-75 years). Inclusion criteria were: 1) no prior whole-brain radiation therapy or resection procedure; 2) a maximum of 4 lesions on preoperative MR imaging; 3) at least 1 cystic lesion; 4) a Karnofsky Performance Scale score >or= 70; and 5) histological diagnosis of a malignant tumor.

Non-small cell lung carcinoma was the primary cancer in most patients (19 patients [63.3%]). A single metastasis was present in 13 patients (43.3%). There was a total of 81 tumors, 33 of which were cystic. Ten patients (33.3%) were in recursive partitioning analysis Class I, and 20 (66.6%) were in Class II. Before drainage the mean tumor volume was 21.8 ml (range 3.8-68 ml); before GKS the mean tumor volume was 10.1 ml (range 1.2-32 ml). The mean prescription dose to the tumor margin was 19.5 Gy (range 12-25 Gy). Overall median patient survival was 15 months. The 1- and 2-year survival rates were 54.7% (95% confidence interval 45.3-64.1%) and 34.2% (95% confidence interval 23.1-45.3%). Local tumor control was achieved in 91.3% of the patients.

The results of this study support the use of a multiple stereotactic approach in cases of multiple and cystic brain metastasis 15).

Case reports

2015

A study describes the first case of histopathologically-confirmed brainstem metastasis originating from lung adenosquamous carcinoma, and discusses the outcomes of treatment by stereotactic aspiration combined with gamma knife radiosurgery (GKRS). A 59-year-old female presented with a cystic mass (15×12×13 mm; volume, 1.3 cm3) located in the pons, two years following surgical treatment for adenosquamous carcinoma of the lung. The patient received initial GKRS for the lesion in the pons with a total dose of 54.0 Gy, however, the volume of the mass subsequently increased to 3.9 cm3 over a period of three months. Computed tomography-guided stereotactic biopsy and aspiration of the intratumoral cyst were performed, yielding 2.0 cm3 of yellow-white fluid. Histology confirmed the diagnosis of adenosquamous carcinoma. Aspiration provided immediate symptomatic relief, and was followed one week later by repeat GKRS with a dose of 12.0 Gy. The patient survived for 12 months following the repeat GKRS; however, later succumbed to the disease after lapsing into a two-week coma. The findings of this case suggest that stereotactic aspiration of cysts may improve the effects of GKRS for the treatment of cystic brainstem metastasis; the decrease in tumor volume allowed a higher radiation dose to be administered with a lower risk of radiation-induced side effects. Therefore, stereotactic aspiration combined with GKRS may be an effective treatment for brainstem metastasis originating from adenosquamous carcinoma 16).

2009

A 71-year-old man who was admitted to the emergency department after an episode of loss of consciousness. On neurological examination a left hemiparesis was observed. The patient’s previous history entailed a total cystectomy and radical prostatectomy 7 months ago because of a transitional cell carcinoma (TCC) of the urinary bladder. Brain imaging work-up revealed a cystic lesion with perifocal edema in the right frontal lobe. The patient was operated and the histological diagnosis was consistent with a metastatic carcinoma, with morphological, histochemical and immunohistochemical features comparable to those of the primary tumor. Postoperative the patient was in excellent neurological state and received complementary chemotherapy and total brain irradiation. Additional imaging and laboratory examinations excluded other metastatic lesion. The patient died 18 months later due to systemic disease. Although intracranial metastases from TCC of urinary bladder have a low incidence, in follow-up examinations any alterations in neurological status in these patients should be thoroughly evaluated 17).


Cystic brain metastases from small-cell lung carcinomas are exceedingly rare and neurosurgical operations are not suitable for those cases considering invisible micrometastases. A 34-year-old female patient presented with small-cell lung carcinoma that metastasized to the brain as a solitary cyst with a thin wall 24 months after a good partial response to initial chemoradiotherapy. The brain mass volume and the main symptom of left hemiplegia, which made the Karnofsky performance status (KPS) fall to 30%, did not respond to whole brain irradiation. Therefore, an Ommaya reservoir was inserted, which dramatically improved the KPS to 70%. This minimally invasive surgical strategy is suitable even for patients with a poorer KPS bearing cystic brain metastases 18).

References

1)

Kim MS, Lee SI, Sim SH. Brain tumors with cysts treated with Gamma Knife radiosurgery: is microsurgery indicated? Stereotact Funct Neurosurg. 1999;72 Suppl 1:38-44. PubMed PMID: 10681689.
2)

Stem K. Chemical study of fluids obtained from cerebral cysts: Report on 56 cases. Brain. 1939;62:88. doi: 10.1093/brain/62.1.88.
3)

CUMINGS JN. The chemistry of cerebral cysts. Brain. 1950 Jun;73(2):244-50. PubMed PMID: 14791790.
4)

GARDNER WJ, COLLIS JS Jr, LEWIS LA. Cystic brain tumors and the blood-brain barrier. Comparison of protein fractions in cyst fluids and sera. Arch Neurol. 1963 Mar;8:291-8. PubMed PMID: 13946556.
5)

Ishikawa E, Yamamoto M, Saito A, Kujiraoka Y, Iijima T, Akutsu H, Matsumura A. Delayed cyst formation after gamma knife radiosurgery for brain metastases. Neurosurgery. 2009 Oct;65(4):689-94; discussion 694-5. doi: 10.1227/01.NEU.0000351771.46273.22. PubMed PMID: 19834373.
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Ramanathan N, Kamaruddin KA, Othman A, Mustafa F, Awang MS. Cystic Meningioma Masquerading as a Metastatic Tumor: A Case Report. Malays J Med Sci. 2016 May;23(3):92-4. PubMed PMID: 27418876; PubMed Central PMCID: PMC4934725.
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Kim M, Cheok S, Chung LK, Ung N, Thill K, Voth B, Kwon DH, Kim JH, Kim CJ, Tenn S, Lee P, Yang I. Characteristics and treatments of large cystic brain metastasis: radiosurgery and stereotactic aspiration. Brain Tumor Res Treat. 2015 Apr;3(1):1-7. doi: 10.14791/btrt.2015.3.1.1. Epub 2015 Apr 29. Review. PubMed PMID: 25977901; PubMed Central PMCID: PMC4426272.
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Oshima A, Kimura T, Akabane A, Kawai K. Optimal implantation of Ommaya reservoirs for cystic metastatic brain tumors preceding Gamma Knife radiosurgery. J Clin Neurosci. 2017 May;39:199-202. doi: 10.1016/j.jocn.2016.12.042. Epub 2017 Jan 20. PubMed PMID: 28117259.
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Lee SR, Oh JY, Kim SH. Gamma Knife radiosurgery for cystic brain metastases. Br J Neurosurg. 2016;30(1):43-8. doi: 10.3109/02688697.2015.1039489. Epub 2015 May 11. PubMed PMID: 25958957.
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Wang H, Qi S, Dou C, Ju H, He Z, Ma Q. Gamma Knife radiosurgery combined with stereotactic aspiration as an effective treatment method for large cystic brain metastases. Oncol Lett. 2016 Jul;12(1):343-347. Epub 2016 May 18. PubMed PMID: 27347148; PubMed Central PMCID: PMC4907086.
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Jung TY, Kim IY, Jung S, Jang WY, Moon KS, Park SJ, Lim SH. Alternative treatment of stereotactic cyst aspiration and radiosurgery for cystic brain metastases. Stereotact Funct Neurosurg. 2014;92(4):234-41. doi: 10.1159/000362935. Epub 2014 Aug 19. PubMed PMID: 25138737.
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Ebinu JO, Lwu S, Monsalves E, Arayee M, Chung C, Laperriere NJ, Kulkarni AV, Goetz P, Zadeh G. Gamma knife radiosurgery for the treatment of cystic cerebral metastases. Int J Radiat Oncol Biol Phys. 2013 Mar 1;85(3):667-71. doi: 10.1016/j.ijrobp.2012.06.043. Epub 2012 Aug 9. PubMed PMID: 22885145.
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Higuchi F, Kawamoto S, Abe Y, Kim P, Ueki K. Effectiveness of a 1-day aspiration plus Gamma Knife surgery procedure for metastatic brain tumor with a cystic component. J Neurosurg. 2012 Dec;117 Suppl:17-22. doi: 10.3171/2012.7.GKS121001. PubMed PMID: 23205784.
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Update: Atypical meningioma

Atypical meningioma (AM)

Atypical (WHO Grade IImeningiomas comprise a heterogeneous group of tumors, with histopathology delineated under the guidance of the WHO and a spectrum of clinical outcomes.

In atypical meningiomas bone involvement and large meningioma peritumoral edema are associated with increased tumor progression.

Classification

Intracranial atypical meningiomas

Spinal atypical meningiomas

Epidemiology

Approximately 15-20% of meningiomas are atypical, meaning that the tumor cells do not appear typical or normal. Atypical meningiomas are neither malignant (cancerous) nor benign, but may become malignant.

Treatment

The treatment of atypical meningioma remains controversial and under-investigated in prospective studies. The roles of surgery, radiation therapy, radiosurgery, and chemotherapy have been incompletely delineated. This has left physicians to decipher how they should treat patients on a case-by-case basis.

In a study, Sun et al. review the English-language literature on the management and clinical outcomes using the WHO 2000/2007 grading criteria. Twenty-two studies for AMs were examined in detail. The authors examined clinical decision points using the literature and concepts from evidence-based medicine. Acknowledging the retrospective nature of the studies, the authors did find evidence for the following clinical strategies:

1) maximal safe resection

2) active surveillance after gross-total resection

3) adjuvant radiation therapy after subtotal resection of AM, especially in the absence of putative radio resistant features 1).

Postoperative radiotherapy

Atypical meningiomas are increasingly irradiated, even after complete or near-complete microsurgical resection despite data that suggests that close observation remains reasonable in the setting of aggressive microsurgical resection.

The efficacies of adjuvant stereotactic radiosurgery (SRS) and external beam radiation therapy (EBRT) for atypical meningiomas (AMs) after subtotal resection (STR) remain unclear.

Conformal, high dose radiotherapy resulted in significant improvement of local control for atypical and malignant meningiomas. Increased local control resulted also in improved rates of survival for patients with malignant meningioma 2).

Role of necrosis

Adjuvant radiation therapy or external beam radiation therapy (EBRT) improved local control after stereotactic radiosurgery STR but only for tumors without spontaneous necrosis. Spontaneous necrosis may aid in decisions to administer adjuvant SRS or EBRT after STR of AMs 3).

Necrosis may be a negative predictor of radiation response regardless of radiation timing or modality 4).

Recurrence

Grade II atypical meningiomas tend to recur and grow faster.

Retrospective series supports the observation that postoperative radiotherapy likely results in lower recurrence rates of gross totally resected atypical meningiomas.

Patients older than 55 years and those with mitoses noted during pathological examination had a significant risk of recurrence after GTR; for these patients, postoperative radiotherapy is recommended 5).

After GTR without postoperative radiation, AMs have a high recurrence rate. Most recurrences occurred within 5 years after resection. Recurrences caused numerous reoperations per patient and shortened survival 6).

A multicenter prospective trial will ultimately be needed to fully define the role of radiotherapy in managing gross totally resected atypical meningiomas 7).

Study limitations, including inadequate statistical power, may underlie the studies’ inability to demonstrate a statistically significant benefit for adjuvant radiotherapy in AM. Because these tumors preferentially recur within 5 years of surgical resection, future studies should define whether early adjuvant therapy should become part of the standard treatment paradigm for completely excised tumors 8).

Brain invasion and high mitotic rates may predict recurrence. After gross total resection (GTR) of AMs, EBRT appears not to affect progression free survival and overall survival, suggesting that observation rather than EBRT may be indicated after GTR 9).

Outcome

The rarity and the inconsistent criteria for defining atypical meningioma prior to the WHO 2007 classification made its management and prognostic factors poorly understood. Only few articles have addressed the survival rates of WHO-classified atypical meningiomas. The small number or the disproportionate representation of irradiated patients was a weakness for these articles.

The most important prognostic factor in determining recurrence was Simpson grading. There was no statistically significant impact of adjuvant radiotherapy on the recurrence of atypical meningiomas. Metaanalysis for the existing literature is needed 10).

Case series

2017

The National Cancer Database was used to identify 2515 patients who were diagnosed with AM between 2009 and 2012 and underwent STR or GTR with or without adjuvant RT. Propensity score matching was first applied to balance covariates including age, year of diagnosis, sex, race, histology, and tumor size in STR or GTR cohorts stratified by adjuvant RT status. Multivariate regression according to the Cox proportional hazards model and Kaplan-Meier survival plots with log-rank test were then used to evaluate OS difference associated with adjuvant RT.

GTR is associated with improved OS compared with STR. In the subgroup analysis, adjuvant RT in patients who underwent STR demonstrated significant association with improved OS compared with no adjuvant RT (adjusted hazard ratio [AHR] 0.590, P = .045); however, adjuvant RT is not associated with improved OS in patients who underwent GTR (AHR 1.093, P = .737).

Despite the lack of consensus on whether adjuvant RT reduces recurrence after surgical resection of AM, our study observed significantly improved OS with adjuvant RT compared with no adjuvant RT after STR 11).

2016

Real-Peña et al published 27 patients with pathological diagnosis of atypical meningioma, and who had a minimum follow-up time of 6 months after diagnosis. Later prognostic factors (age <50years, male gender, bone involvement, peri-lesional swelling, tumour volume, location, Ki67/MIB-1) were evaluated after the stratification of patients undergoing complete resection in recurrencies and non-recurrencies. Univariate analysis was performed using Mann-Whitney test, χ(2) homogeneity test/Fisher exact test. Finally, multivariate analysis was performed using binary logistic regression to obtain the values for R(2) Nagelkerke and the Hosmer-Lemeshow to evaluate the goodness of fit.

The uni- and multivariate analysis showed no statistically significant differences between recurrent and non-recurrent subgroups of patients undergoing complete resection. It is noted in the results that for each year of age above 50 years, the risk of recurrence is decreased by 5.8%.

Although current prognostic factors may show an increased risk of recurrence once patients are stratified by the two most important factors (pathology and extent of resection), those factors are insufficient to predict the ultimate outcome of patients affected by this pathology 12)


Endo et al., reviewed 45 patients with atypical meningioma who underwent surgical intervention between January 2000 and December 2013. The mean age of the patients and mean follow-up period was 58.7 years and 81.0 months, respectively. Analyses included factors such as patient age, gender, location and size of tumor, extent of surgical resection (Simpson Grading System), and MIB-1 index (LI). Univariate analysis was used to detect prognostic factors associated with recurrence and survival.

The 5-year recurrence-free rate for all 45 patients was 58.4 %; 5- and 10-year survival rates were 83.2 % and 79.9 %, respectively. In univariate analyses, age >60 years, and MIB-1 LI correlated with disease recurrence, whereas age >60 years, subtotal surgical resection, MIB-1 LI, and indication for radiotherapy correlated with death. MIB-1 LI levels higher than 12.8 % and 19.7 % predicted recurrence and death, respectively. In our cohort, 26 patients received postoperative radiotherapy including conventional radiation (n = 21) or gamma knife radiosurgery (n = 5). Postoperative radiotherapy did not decrease recurrence rates in our cohort (p = 0.63). Six and two patients who died during the study period underwent conventional radiation and radiosurgery, respectively.

Age, male gender, extent of surgical resection, and higher MIB-1 LI influenced the outcome of atypical meningioma. In our cohort, postoperative radiotherapy failed to provide long-term tumor control. Following incomplete surgical resection of atypical meningioma in elderly patients, adjuvant postoperative radiotherapy may not be an ideal treatment option, particularly when MIB-1 LI is higher than 19.7 % 13).


44 WHO Grade II and 9 WHO Grade III meningiomas treated by CyberKnife for adjuvant or salvage therapy. Patient demographics, treatment parameters, local control, regional control, locoregional control, overall survival, radiation history, and complications were documented.

For WHO Grade II patients, recurrence occurred in 41%, with local, regional, and locoregional failure at 60 months recorded as 49%, 58% and 36%, respectively. For WHO Grade III patients, recurrence occurred in 66%, with local, regional, and locoregional failure at 12 months recorded as 57%, 100%, and 43%. The 60-month locoregional control rates for radiation naïve and experienced patients were 48% and 0% (p = 0.14), respectively. Overall, 7 of 44 Grade II patients and 8 of 9 Grade III patients had died at last follow-up. The 60-month and 12-month overall survival rates for Grade II and III meningioma were 87% and 50%, respectively. Serious complications occurred in 7.5% of patients.

SRS for adjuvant and salvage treatment of WHO Grade II meningioma by a hypofractionated plan is a viable treatment strategy with acceptable long-term tumor control, overall survival, and complication rates. Future work should contribute additional study toward the radiation naïve and the local management of malignant meningioma 14).


A triple center case-note review of adults with newly-diagnosed atypical meningiomas between 2001 and 2010 was performed. Pathology diagnosis was made according to the World Health Organization classification in use at the time of surgery. Patients with multiple meningiomas, neurofibromatosis type 2 and radiation-induced meningiomas were excluded. Extent of resection was defined as gross total resection (GTR; Simpson Grade I-III) or subtotal resection (STR; Simpson Grade IV-V). Survival analysis was performed using the Kaplan-Meier method. One hundred thirty-three patients were identified with a median age of 62years (range 22-86years) and median follow-up of 57.4months (range 0.1-152.2months). Tumors were mostly located in the convexity (50.4%) or falcine/parasagittal regions (27.1%). GTR (achieved in 85%) was associated with longer progression free survival (PFS) (5year PFS 81.2% versus 40.08%, log-rank=11.117, p=0.001) but not overall survival (OS) (5year OS 76.6% versus 39.7%, log-rank=3.652, p=0.056). Following GTR, early adjuvant radiotherapy was administered to 28.3% of patients and did not influence OS (5year OS 77.0% versus 75.7%, log-rank=0.075, p=0.784) or PFS (5year PFS 82.0% versus 79.3%, log-rank=0.059, p=0.808). Although extent of resection emerged as an important prognostic variable, early adjuvant radiotherapy did not influence outcome following GTR of atypical meningiomas. Prospective randomized controlled trials are planned 15).

2015

Twenty-eight patients with skull base atypical meningiomas underwent microsurgical resection between June 2001 and November 2009. The clinical characteristics of the patients and meningiomas, the extent of surgical resection, and complications after treatment were retrospectively analyzed.

Thirteen patients (46.4%) had disease recurrence or progression during follow up time. The median time to disease progression was 64 months. The extent of the surgical resection significantly impacted prognosis. Gross total resection (GTR) of the tumor improved progression free survival (PFS) compared to subtotal resection (STR, p = 0.011). An older patient age at diagnosis also resulted in a worse outcome (p = 0.024). An MIB-1 index <8% also contributed to improved PFS (p = 0.031). None of the patients that underwent GTR and received adjuvant radiotherapy had tumors recur during follow up. STR with adjuvant radiotherapy tended to result in better local tumor control than STR alone (p = 0.074). Three of 28 patients (10.7%) developed complications after microsurgery. The GTR group had a higher rate of complications than those with STR. There were no late adverse effects after adjuvant radiotherapy during follow up.

For patients with skull base atypical meningiomas, GTR is desirable for longer PFS, unless radical excision is expected to lead to severe complications. Adjuvant radiation therapy is advisable to reduce tumor recurrence regardless of the extent of surgical resection. Age of disease onset and the MIB-1 index of the tumor were both independent prognostic factors of clinical outcome 16).


A retrospective analysis of the patients operated at the Clinic of Neurosurgery, Clinical Center of Serbia, Belgrade, between January 1st 1995 and December 31th 2006 was performed. In that period 88 lesions met the histological criteria for atypical (75) and anaplastic (13) meningioma. Postoperative radiotherapy was conducted in 63.6% of patients.

At a median follow-up of 67.4 months in all patients the overall survival was 68 months and five-year survival was about 54.5%. The median survival was 76 months with surgery and adjuvant radiotherapy and 40 months with surgery alone (Log rank=7.4; p=0.006). Recurrent disease occurred in 58 patients (65.9%). Median time between first surgery and tumor recurrence in patients undergoing radiotherapy was 51 months, while in non-irradiated group 24 months (Log rank=17.7; p˂0.001). Multivariate analysis identified as recurrence-predicting factors anaplastic histotype (hazard ratio=2,9; p=0,003) and postoperative radiotherapy (hazard ratio=4,5; p<0,001).

The addition of adjuvant radiotherapy to surgery for atypical and anaplastic meningiomas resulted in a clinically meaningful and statistically significant survival benefit 17).

Case reports

Only two prior cases of benign dendritic melanocytes colonizing a meningioma have been reported.

Dehghan Harati et al. add a third case, describe clinicopathologic features shared by the three, and elucidate the risk factors for this very rare phenomenon. A 29 year-old Hispanic woman presented with headache and hydrocephalus. MRI showed a lobulated enhancing pineal region mass measuring 41 mm in greatest dimension. Subtotal resection of the mass demonstrated an atypical meningioma, WHO grade II, and the patient subsequently underwent radiotherapy. She presented 4 years later with diplopia, and MRI showed an enhancing extra-axial mass measuring 47 mm in greatest dimension and centered on the tentorial incisura. Subtotal resection showed a brain-invasive atypical meningioma with melanocytic colonization. The previous two cases in the literature were atypical meningiomas, one of which was also brain invasive. Atypical meningiomas may be at particular risk for melanocytic colonization as they upregulate molecules known to be chemoattractants for melanocytes. We detected c-Kit expression in a minority of the melanocytes as well as stem cell factor and basic fibroblast growth factor in the meningioma cells, suggesting that mechanisms implicated in normal melanocyte migration may be involved. In some cases, brain invasion with disruption of the leptomeningeal barrier may also facilitate migration from the subarachnoid space into the tumor. Whether there is low-level proliferation of the dendritic melanocytes is unclear. Given that all three patients were non-Caucasian, meningiomas in persons and/or brain regions with increased dendritic melanocytes may predispose to colonization. The age range spanned from 6 years old to 70 years old. All three patients were female. The role of gender and estrogen in the pathogenesis of this entity remains to be clarified. Whether melanocytic colonization may also occur in the more common Grade I meningiomas awaits identification of additional cases 18).

References

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Sun SQ, Hawasli AH, Huang J, Chicoine MR, Kim AH. An evidence-based treatment algorithm for the management of WHO Grade II and III meningiomas. Neurosurg Focus. 2015 Mar;38(3):E3. doi: 10.3171/2015.1.FOCUS14757. PubMed PMID: 25727225.
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Hug EB, Devries A, Thornton AF, Munzenride JE, Pardo FS, Hedley-Whyte ET, Bussiere MR, Ojemann R. Management of atypical and malignant meningiomas: role of high-dose, 3D-conformal radiation therapy. J Neurooncol. 2000 Jun;48(2):151-60. PubMed PMID: 11083080.
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Sun SQ, Cai C, Murphy RK, DeWees T, Dacey RG, Grubb RL, Rich KM, Zipfel GJ, Dowling JL, Leuthardt EC, Leonard JR, Evans J, Simpson JR, Robinson CG, Perrin RJ, Huang J, Chicoine MR, Kim AH. Management of atypical cranial meningiomas, part 2: predictors of progression and the role of adjuvant radiation after subtotal resection. Neurosurgery. 2014 Oct;75(4):356-63. doi: 10.1227/NEU.0000000000000462. PubMed PMID: 24932708.
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Sun SQ, Cai C, Murphy RK, DeWees T, Dacey RG, Grubb RL, Rich KM, Zipfel GJ, Dowling JL, Leuthardt EC, Simpson JR, Robinson CG, Chicoine MR, Perrin RJ, Huang J, Kim AH. Radiation Therapy for Residual or Recurrent Atypical Meningioma: The Effects of Modality, Timing, and Tumor Pathology on Long-Term Outcomes. Neurosurgery. 2016 Jul;79(1):23-32. doi: 10.1227/NEU.0000000000001160. PubMed PMID: 26645969.
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Lee KD, DePowell JJ, Air EL, Dwivedi AK, Kendler A, McPherson CM. Atypical meningiomas: is postoperative radiotherapy indicated? Neurosurg Focus. 2013 Dec;35(6):E15. doi: 10.3171/2013.9.FOCUS13325. PubMed PMID: 24289123.
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Komotar RJ, Iorgulescu JB, Raper DM, Holland EC, Beal K, Bilsky MH, Brennan CW, Tabar V, Sherman JH, Yamada Y, Gutin PH. The role of radiotherapy following gross-total resection of atypical meningiomas. J Neurosurg. 2012 Oct;117(4):679-86. doi: 10.3171/2012.7.JNS112113. Epub 2012 Aug 24. PubMed PMID: 22920955.
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Kaur G, Sayegh ET, Larson A, Bloch O, Madden M, Sun MZ, Barani IJ, James CD, Parsa AT. Adjuvant radiotherapy for atypical and malignant meningiomas: a systematic review. Neuro Oncol. 2014 May;16(5):628-36. doi: 10.1093/neuonc/nou025. Epub 2014 Apr 2. PubMed PMID: 24696499; PubMed Central PMCID: PMC3984561.
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Sun SQ, Kim AH, Cai C, Murphy RK, DeWees T, Sylvester P, Dacey RG, Grubb RL, Rich KM, Zipfel GJ, Dowling JL, Leuthardt EC, Leonard JR, Evans J, Simpson JR, Robinson CG, Perrin RJ, Huang J, Chicoine MR. Management of atypical cranial meningiomas, part 1: predictors of recurrence and the role of adjuvant radiation after gross total resection. Neurosurgery. 2014 Oct;75(4):347-55. doi: 10.1227/NEU.0000000000000461. PubMed PMID: 24932707.
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Hammouche S, Clark S, Wong AH, Eldridge P, Farah JO. Long-term survival analysis of atypical meningiomas: survival rates, prognostic factors, operative and radiotherapy treatment. Acta Neurochir (Wien). 2014 Aug;156(8):1475-81. doi: 10.1007/s00701-014-2156-z. Epub 2014 Jun 26. PubMed PMID: 24965072.
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Wang C, Kaprealian TB, Suh JH, Kubicky CD, Ciporen JN, Chen Y, Jaboin JJ. Overall survival benefit associated with adjuvant radiotherapy in WHO grade II meningioma. Neuro Oncol. 2017 Mar 24. doi: 10.1093/neuonc/nox007. [Epub ahead of print] PubMed PMID: 28371851.
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Update: Rehabilitation after lumbar disc surgery

Rehabilitation after lumbar disc surgery

Studies have shown late post-operative physical disability and residual pain in patients following lumbar disc surgery despite growing evidence of its beneficial effects. Therefore, rehabilitation is required to minimise the late postoperative complications.

Several rehabilitation programmes are available for individuals after lumbar disc surgery.

Cochrane review in 2009 showed that exercise programs starting 4 to 6 weeks postsurgery seem to lead to a faster decrease in pain and disability than no treatment. High intensity exercise programs seem to lead to a faster decrease in pain and disability than low intensity programs. There were no significant differences between supervised and home exercises for pain relief, disability, or global perceived effect. There is no evidence that active programs increase the reoperation rate after first-time lumbar surgery 1) 2).


metaanalysis in 2014 showed considerable variation in the content, duration and intensity of the rehabilitation programmes, and for none of them was high- or moderate-quality evidence identified. Exercise programmes starting four to six weeks postsurgery seem to lead to a faster decrease in pain and disability than no treatment, with small to medium effect sizes, and high-intensity exercise programmes seem to lead to a slightly faster decrease in pain and disability than is seen with low-intensity programmes, but the overall quality of the evidence is only low to very low. No significant differences were noted between supervised and home exercise programmes for pain relief, disability or global perceived effect. None of the trials reported an increase in reoperation rate after first-time lumbar surgery. High-quality randomised controlled trials are strongly needed 3).


A Multicentre, randomised, controlled trial, and economic evaluation with concealed allocation and intention-to-treat-analysis in adults who underwent discectomy for a herniated lumbar disc, confirmed by magnetic resonance imaging, and signs of nerve root compression corresponding to the herniation level.

Early rehabilitation (exercise therapy) for 6 to 8 weeks, versus no referral, immediately after discharge.

In line with the recommended core outcome set, the co-primary outcomes were: functional status (Oswestry Disability Index); leg and back pain (numerical rating scale 0 to 10); global perceived recovery (7-point Likert scale); and general physical and mental health (SF12), assessed 3, 6, 9, 12 and 26 weeks after surgery. The outcomes for the economic evaluation were quality of life and costs, measured at 6, 12 and 26 weeks after surgery.

There were no clinically relevant or statistically significant overall mean differences between rehabilitation and control for any outcome adjusted for baseline characteristics: global perceived recovery (OR 1.0, 95% CI 0.6 to 1.7), functional status (MD 1.5, 95% CI -3.6 to 6.7), leg pain (MD 0.1, 95% CI -0.7 to 0.8), back pain (MD 0.3, 95% CI -0.3 to 0.9), physical health (MD -3.5, 95% CI -11.3 to 4.3), and mental health (MD -4.1, 95% CI -9.4 to 1.3). After 26 weeks, there were no significant differences in quality-adjusted life years (MD 0.01, 95% CI -0.02 to 0.04 points) and societal costs (MD -€527, 95% CI -2846 to 1506). The maximum probability for the intervention to be cost-effective was 0.75 at a willingness-to-pay of €32 000/quality-adjusted life year.

Early rehabilitation after lumbar disc surgery was neither more effective nor more cost-effective than no referral 4).

Case series

2017

Twenty-one patients aged 25-65 years undergoing lumbar microdiscectomy were randomly assigned to the rehabilitation group (n = 14) or active control group (n = 7) by simple randomisation. Eight rehabilitation sessions were initiated 2-3 weeks after surgery. Thirty-minute sessions were conducted twice weekly for four weeks. Post-operative physical disability and pain were assessed at baseline and at the two-year follow-up.

Post-operative physical disability improved more in patients who had undergone rehabilitation than in those who had received control care (63% vs. -23%, P< 0.05). Post-operative residual low back and leg pain were alleviated in the treatment group (26% and 57%, respectively), but intensified in the control group (-5% and -8%, respectively).

This study demonstrated the potential of manipulative rehabilitation and importance of post-operative management after lumbar disc surgery. Definitive trials with larger sample sizes are required to confirm the feasibility and potential therapeutic effectiveness of this approach 5).


A study aimeds to investigate (1) motives, motivations and expectations regarding the choice for a specific rehabilitation setting after herniated disc surgery and (2) how rehabilitation-related motivations and expectations are associated with rehabilitation outcome (ability to work, health-related quality of life and satisfaction with rehabilitation) three months after disc surgery.

The longitudinal cohort study refers to 452 disc surgery patients participating in a subsequent rehabilitation. Baseline interviews took part during acute hospital stay (pre-rehabilitation), follow-up interviews three months later (post-rehabilitation). Binary logistic regression and multiple linear regression analyses were applied.

(1) Motives, motivations and expectations: Inpatient rehabilitation (IPR) patients stated “less effort/stress” (40.9%), more “relaxation and recreation” (39.1%) and greater “intensity of care and treatment” (37.0%) regarding their setting preference, whereas outpatient rehabilitation (OPR) patients indicated “family reasons” (45.3%), the wish for “staying in familiar environment” (35.9%) as well as “job-related reasons” (11.7%) as most relevant. IPR patients showed significantly higher motivation/expectation scores regarding regeneration (p < .001), health (p < .05), coping (p < .001), retirement/job (p < .01), psychological burden (p < .05) and physical burden (p < .001) compared to OPR patients. (2) Associations with rehabilitation outcome: Besides other factors (e.g. age, gender and educational level) rehabilitation-related motivations/expectations were significantly associated with rehabilitation outcome measures. For example, patients with less motivations/expectations to achieve improvements regarding “physical burden” showed a better health-related quality of life (p < .01) three months after disc surgery. Less motivations/expectations to achieve improvements regarding “psychological burden” was linked to a better mental health status (p < .001) and a greater satisfaction with rehabilitation (OR = .806; p < .05).

Rehabilitation-related motivations and expectations differed substantially between IPR and OPR patients before rehabilitation and were significantly associated with rehabilitation outcome. Taking motivational and expectation-related aspects into account may help to improve allocation procedures for different rehabilitation settings and may improve rehabilitation success 6).

2016

Twenty-one patients aged 25-69 years who underwent lumbar microdiscectomy were randomised to either the manipulative rehabilitation treatment group or the active control group. Rehabilitation was initiated 2-3 weeks after surgery, twice a week for 4 weeks. Each session was for 30 minutes. Primary outcomes were the Roland-Morris disability questionnaire and the visual analogue pain scale. Outcome measures were assessed at baseline and post-intervention.

Early post-operative physical disability was improved with a 55% reduction by early individualised manipulative rehabilitation, compared to that of control care with a 5% increase. Early post-operative residual leg pain decreased with rehabilitation (55%) and control care (9%).

This pilot study supports the feasibility of a future definitive randomised control trial and indicates this type of rehabilitation may be an important option for post-operative management after spinal surgery 7).

References

1)

Ostelo RW, Costa LO, Maher CG, de Vet HC, van Tulder MW. Rehabilitation after lumbar disc surgery. Cochrane Database Syst Rev. 2008 Oct 8;(4):CD003007. doi: 10.1002/14651858.CD003007.pub2. Review. Update in: Cochrane Database Syst Rev. 2014;3:CD003007. PubMed PMID: 18843637.
2)

Ostelo RW, Costa LO, Maher CG, de Vet HC, van Tulder MW. Rehabilitation after lumbar disc surgery: an update Cochrane review. Spine (Phila Pa 1976). 2009 Aug 1;34(17):1839-48. doi: 10.1097/BRS.0b013e3181abbfdf. Review. PubMed PMID: 19602996.
3)

Oosterhuis T, Costa LO, Maher CG, de Vet HC, van Tulder MW, Ostelo RW. Rehabilitation after lumbar disc surgery. Cochrane Database Syst Rev. 2014 Mar 14;(3):CD003007. doi: 10.1002/14651858.CD003007.pub3. Review. PubMed PMID: 24627325.
4)

Oosterhuis T, Ostelo RW, van Dongen JM, Peul WC, de Boer MR, Bosmans JE, Vleggeert-Lankamp CL, Arts MP, van Tulder MW. Early rehabilitation after lumbar disc surgery is not effective or cost-effective compared to no referral: a randomised trial and economic evaluation. J Physiother. 2017 Jul;63(3):144-153. doi: 10.1016/j.jphys.2017.05.016. Epub 2017 Jun 28. PubMed PMID: 28668558.
5)

Kim BJ, Kim T, Ahn J, Cho H, Kim D, Yoon B. Manipulative rehabilitation applied soon after lumbar disc surgery improves late post-operative functional disability: A preliminary 2-year follow-up study. J Back Musculoskelet Rehabil. 2017 May 5. doi: 10.3233/BMR-169546. [Epub ahead of print] PubMed PMID: 28505954.
6)

Löbner M, Stein J, Luppa M, Konnopka A, Meisel HJ, Günther L, Meixensberger J, Stengler K, Angermeyer MC, König HH, Riedel-Heller SG. Choosing the right rehabilitation setting after herniated disc surgery: Motives, motivations and expectations from the patients’ perspective. PLoS One. 2017 Aug 22;12(8):e0183698. doi: 10.1371/journal.pone.0183698. eCollection 2017. PubMed PMID: 28829828.
7)

Kim BJ, Ahn J, Cho H, Kim D, Kim T, Yoon B. Early individualised manipulative rehabilitation following lumbar open laser microdiscectomy improves early post-operative functional disability: A randomized, controlled pilot study. J Back Musculoskelet Rehabil. 2016;29(1):23-9. doi: 10.3233/BMR-150591. PubMed PMID: 25792303.

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).

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