Knobloch syndrome

Knobloch syndrome

Knobloch syndrome (KS) is a rare autosomal recessive disorder associated with multiple ocular and cranial abnormalities. Occult occipital skull defect or encephalocele should raise suspicion of this disease. It is never reported in neurosurgical literature, possibly due to a lack of clinician familiarity, leading to underdiagnosis and inadequate management.


Four patients originally presented for genetic evaluation of symptomatic structural brain malformations. Whole-genome genotyping, whole-exome sequencing, and confirmatory Sanger sequencing were performed. Using immunohistochemical analysis, Caglayan et al. investigated the protein expression pattern of COL18A1 in the mid-fetal and adult human cerebral cortex and then analyzed the spatial and temporal changes in the expression pattern of COL18A1 during human cortical development using the Human Brain Transcriptome database.

They identified two novel homozygous deleterious frame-shift mutations in the COL18A1 gene. On further investigation of these patients and their families, they found that many exhibited certain characteristics of Knobloch syndrome, including pronounced ocular defects. This data strongly support an important role for COL18A1 in brain development, and this report contributes to an enhanced characterization of the brain malformations that can result from deficiencies of collagen XVIII.

This case series highlights the diagnostic power and clinical utility of whole-exome sequencing technology-allowing clinicians and physician scientists to better understand the pathophysiology and presentations of rare diseases. They suggest that patients who are clinically diagnosed with Knobloch syndrome and/or found to have COL18A1 mutations via genetic screening should be investigated for potential structural brain abnormalities even in the absence of an encephalocele 1).


Venkateshappa reported a patient that also had seizures, which is a sporadic presentation of this syndrome.

They report a clinico-radiologic finding of a 7-year-old boy who presented with seizures, cataracts, and an occipital bone defect along with bilateral subependymal heterotopias and polymicrogyria.

This case highlights the importance of consideration of this syndrome in children with a midline occipital bone defect with or without encephalocele and seizures. Early recognition of this presentation is critical for obtaining access to appropriate genetic counseling and subsequent monitoring and prevention of complications by surgical intervention 2).


1)

Caglayan AO, Baranoski JF, Aktar F, Han W, Tuysuz B, Guzel A, Guclu B, Kaymakcalan H, Aktekin B, Akgumus GT, Murray PB, Erson-Omay EZ, Caglar C, Bakircioglu M, Sakalar YB, Guzel E, Demir N, Tuncer O, Senturk S, Ekici B, Minja FJ, Šestan N, Yasuno K, Bilguvar K, Caksen H, Gunel M. Brain malformations associated with Knobloch syndrome–review of literature, expanding clinical spectrum, and identification of novel mutations. Pediatr Neurol. 2014 Dec;51(6):806-813.e8. doi: 10.1016/j.pediatrneurol.2014.08.025. Epub 2014 Sep 4. PMID: 25456301; PMCID: PMC5056964.
2)

Venkateshappa BM, Raju B, Rallo MS, Jumah F, Suresh SC, Gupta G, Nanda A. Knobloch Syndrome, a Rare Cause of Occipital Encephalocele and Seizures: A Case Report. Pediatr Neurosurg. 2021 Mar 31:1-5. doi: 10.1159/000512719. Epub ahead of print. PMID: 33789317.

Sinus pericranii treatment

Sinus pericranii treatment

Accepted guidelines or recommendations concerning the managementdiagnosis, and treatment of sinus pericranii are still lacking.

Angiography plays a crucial role in the classification of SP and choice of the optimal treatment. Only accessory SP is amenable to treatment, whereas dominant SP must be preserved.

Ellis et al describe a simple and unique method for determining whether intracranial venous outflow may be compromised by sinus pericranii treatment. This involves performing catheter angiography while the lesion is temporarily obliterated by external compression. Analysis of intracranial venous outflow in this setting allows visualization of angiographic changes that will occur once the sinus pericranii is permanently obliterated. Thus, the safety of surgical intervention can be more fully appraised using this technique 1).


There were notable improvements following surgical resection for the abnormal venous lesions and several sclerotherapies 2)


Intraoperative hemostasis is essential while sinus pericranii is detached from the craniumHemostatic agents such as bone wax or absorbable gelatin and heat coagulation seem to be useful. However, complicative hemorrhage concerning to the preceded technique has been also reported. To detect minor shunting points between the sinus pericranii and the intracranial veins, the major venous connection can be manually compressed. Intraoperative manual compression of a major venous connection of sinus pericranii can be an option to manage intraoperative bleeding 3).

The endovascular approach is becoming increasingly relevant and has proven to be safe and effective 4).

The surgical treatment involves the resection of the extracranial venous package and ligation of the emissary communicating vein. In some cases of SP, surgical excision is performed for cosmetic reasons. The endovascular technique has been described by transvenous approach combined with direct puncture and the recently endovascular embolization with Onyx 5).


1)

Ellis JA, Mejia Munne JC, Feldstein NA, Meyers PM. Determination of sinus pericranii resectability by external compression during angiography: technical note. J Neurosurg Pediatr. 2015 Oct 16:1-5. [Epub ahead of print] PubMed PMID: 26474103.
2)

Ryu JY, Lee JH, Lee JS, Lee JW, Lee SJ, Lee JM, Lee SY, Huh S, Kim JY, Hwang SK, Chung HY. Combined treatment of surgery and sclerotherapy for sinus pericranii. Arch Craniofac Surg. 2020 Apr;21(2):109-113. doi: 10.7181/acfs.2019.00521. Epub 2020 Apr 20. PMID: 32380811; PMCID: PMC7206457.
3)

Fujimoto Y, Ishibashi R, Maki Y, Kitagawa M, Kinosada M, Kurosaki Y, Ikeda H, Chin M. A Simple Surgical Technique for Pediatric Sinus Pericranii: Intraoperative Manual Compression of a Major Shunting Point. Pediatr Neurosurg. 2021 Mar 29:1-6. doi: 10.1159/000514478. Epub ahead of print. PMID: 33780955.
4)

Pavanello M, Melloni I, Antichi E, Severino M, Ravegnani M, Piatelli G, Cama A, Rossi A, Gandolfo C. Sinus pericranii: diagnosis and management in 21 pediatric patients. J Neurosurg Pediatr. 2015 Jan;15(1):60-70. doi: 10.3171/2014.9.PEDS13641. PubMed PMID: 25360854.
5)

Rangel-Castilla L, Krishna C, Klucznik R, Diaz O. Endovascular embolization with Onyx in the management of sinus pericranii: a case report. Neurosurg Focus. 2009 Nov;27(5):E13. doi: 10.3171/2009.8.FOCUS09170. PubMed PMID: 19877791.

Lumbosacral Lipomyelomeningocele

Lumbosacral Lipomyelomeningocele

Lipomyelomeningocele, is a closed neural tube defect, that usually occurs in the lumbosacral area as a single lesion but can be associated with other spinal dysraphism 1) and Caudal regression syndrome.

Represent a unique population within the spectrum of spinal dysraphism.

Premature separation of the neuroectoderm from the ipsilateral surface ectoderm allowing mesenchymal tissue to invade into the central canal, or “premature dysjunction” theory, was proposed for the pathogenesis of dorsal type lumbosacral lipoma. To test this theory, the unilateral neural fold was incised using Hamburger and Hamilton stage 12 or 13 chick embryos. Among 35 embryos evaluated, 15 showed abnormal findings, and of these one showed findings which suggested lumbosacral lipoma: a back lump, blending of the neuroepithelium and mesenchyme through indistinct basement membrane and vertebral body abnormalities. The other 14 embryos showed abnormalities including blunt tails, open neural tube defects, incomplete closure of the dorsal neuroepithelium with intact skin, skin dimples, disorganized gray matter, scoliosis, ectopic neuroepithelium and an accessory spinal cord. The results revealed that the incision of the unilateral neural fold in the early chick embryo may produce a lesion suggestive of lumbosacral lipoma, a finding which supports the premature dysjunction theory. This method needs further refinement to overcome technical difficulties, high mortality, and a low yield before being adopted as an experimental model for lumbosacral lipoma 2).

A subcutaneous lipoma that passes through a midline defect in the lumbodorsal fascia, vertebral neural arch, and dura, and merges with an abnormally low tethered cord 3).

The natural history of LMMC remains poorly defined. The description and prevalence of the presenting orthopaedic clinical signs and symptoms for LMMC have been infrequent and often documented only in general terms.

Many patients with lumbosacral lipoma are asymptomatic; however, a significant proportion will have neurological deficits present at birth and most develop neurological symptoms over time.

Implication of these deficits with respect to natural history and management are not well understood.

New dynamic MRI-based parameters to establish the presence and magnitude of tethered cord syndrome (TCS) have been defined. oscillatory frequency (OF) measured the extent of loss of translational cord displacement in supine and prone positions; delta bending angle (ΔBA) defined the relative angulation of conus with lower spinal cord, and sagittal and axial root angles represented ventral nerve root stretching. The difference in OF or ΔBA was minimum in the group with thick filum terminale and progressively increased in the groups with lipomyelomeningocele and meningomyelocele 4)


Butterfly vertebra may be associated.

Untethering surgery.


From Naidich TP, McLone DG, Mutluer S. A new understanding of dorsal dysraphism with lipoma (lipomyeloschisis): radiologic evaluation and surgical correction. AJNR. 1983; 4:103–116 5)

  1. mobilize the subcutaneous mass, it funnels down through the deep fascia

  2. open last intact vertebral arch (work from normal dura)

  3. identify the fibrovascular band that crosses the most cephalic widely bifid lamina

  4. sectioning the fibrovascular band frees the dural tube and releases the sharp kink in the superior surface of the meningocele

  5. taking care to preserve dorsal nerve roots, the dura is incised anterior to the dura-lipoma junction

  6. similar procedure is carried out with arachnoid membrane

  7. dural/arachnoid incisions are continued around entire extent of tethered conus

  8. cord and placode are untethered;

  9. Lipoma is then trimmed as completely as possible, intentionally leaving some fat behind to avoid injury to dorsal surface of placode. Superior extension along dorsal surface of cord or into central canal is debulked as much as is safely possible

  10. the placode is reformed into a closed neural tube

  11. close the pial margins

  12. the dura is closed (primarily if possible, or using fascia lata graft if too much tension is placed on folded placode)


An expansile dural graft should be incorporated in cases of lipomyelomeningocele in which primary dural closure does not permit free flow of CSF 6).


Continuous eCUSA-based stimulation of the cauda equina during LMMC resection is a feasible mapping technique with potential added value improving safety of untethering. Future studies evaluating extension of untethering, as well as the rates of retethering and long-term neurological and urological outcomes, are warranted 7).

The aim of a study is to compare the outcomes of surgical and conservative treatments of pediatric asymptomatic lumbosacral lipomas, and to address whether the patients can benefit from prophylactic surgeries. The literature reports of surgical and conservative treatments of child asymptomatic lumbosacral lipomas were reviewed and collected, and a meta-analysis of the reports regarding the incidence of sphincter and lower limb dysfunctions was performed. A total of five literatures were collected, containing a total of 403 patients, among which 124 patients received conservative treatments with 32 (25.81%) cases developing neurological dysfunctions during follow-up, and 279 received prophylactic surgical treatments with 30 (10.75%) patients developing neurological dysfunctions in follow-up, the difference being statistically significant (P ≤ 0.05). For pediatric asymptomatic lumbosacral lipomas of the three major subtypes, the limited source of literature so far suggests that prophylactic surgery is superior to conservative strategy in preventing the patients from neurological deterioration. Larger patient cohorts, randomized studies, and longer length of follow-ups are needed for further corroboration 8).

Lumbosacral lipomyelomeningocele case series.

Lumbosacral Lipomyelomeningocele with Lateral Attachment to Neural Placode 9).


Fetal lipomyelomeningocele was suspected during the second-trimester ultrasound and confirmed by magnetic resonance imaging. The pregnancy took its course and a term neonate was delivered. At 2 years of age lipomyelomeningocele surgical removal was performed. The patient is now 4 years old and, despite neurogenic bladder, is a healthy boy with normal psychomotor development for his age. This case illustrates the favorable prognosis of this entity and the importance of prompt diagnosis and multidisciplinary counseling 10).


A patient with lipomyelomeningocele (known in utero) presented for MRI characterization prior to surgical procedure at three months of age. Cross-sectional imaging revealed a spinal dysraphism of the lower lumbar spine, with a posterior spinal defect spanning L4 to S2 subcutaneous fat intrusion, and distal spinal cord extrusion. An osseous excrescence was also appreciated, articulating with the left iliac bone. This case demonstrates the youngest known lipomyelomeningocele with accessory limb and the abnormal growth of multiple tissue types at the site of spinal dysraphism-a potential consequence of dedifferentiated cell proliferation originating from a secondary neural tube defect or rachipagus parasitic twinning 11)


1)

Hanif H, Khanbabazadeh S, Nejat F, El Khashab M. Tethered cord with tandem lipomyelomeningoceles, split cord malformation and thick filum. J Pediatr Neurosci. 2013 Sep;8(3):204-6. doi: 10.4103/1817-1745.123665. PubMed PMID: 24470813.
2)

Li YC, Shin SH, Cho BK, Lee MS, Lee YJ, Hong SK, Wang KC. Pathogenesis of lumbosacral lipoma: a test of the “premature dysjunction” theory. Pediatr Neurosurg. 2001 Mar;34(3):124-30. PubMed PMID: 11359100.
3)

Emery JL, Lendon RG. Lipomas of the Cauda Equina and Other Fatty Tumors Related to Neurospinal Dysraphism.DevMedChildNeurol.1969;11:62–70
4)

Singh S, Behari S, Singh V, Bhaisora KS, Haldar R, Krishna Kumar G, Mishra P, Phadke RV. Dynamic magnetic resonance imaging parameters for objective assessment of the magnitude of tethered cord syndrome in patients with spinal dysraphism. Acta Neurochir (Wien). 2018 Nov 20. doi: 10.1007/s00701-018-3721-7. [Epub ahead of print] PubMed PMID: 30456429.
5)

Naidich TP, McLone DG, Mutluer S. A new understanding of dorsal dysraphism with lipoma (lipomyeloschisis): radiologic evaluation and surgical correction. AJNR. 1983; 4:103–116
6)

Alexiades NG, Ahn ES, Blount JP, Brockmeyer DL, Browd SR, Grant GA, Heuer GG, Hankinson TC, Iskandar BJ, Jea A, Krieger MD, Leonard JR, Limbrick DD Jr, Maher CO, Proctor MR, Sandberg DI, Wellons JC 3rd, Shao B, Feldstein NA, Anderson RCE. Development of best practices to minimize wound complications after complex tethered spinal cord surgery: a modified Delphi study. J Neurosurg Pediatr. 2018 Sep 14:1-9. doi: 10.3171/2018.6.PEDS18243. [Epub ahead of print] PubMed PMID: 30215584.
7)

Sapir Y, Buzaglo N, Korn A, Constantini S, Roth J, Rochkind S. Dynamic mapping using an electrified ultrasonic aspirator in lipomyelomeningocele and spinal cord detethering surgery-a feasibility study. Childs Nerv Syst. 2021 Jan 6. doi: 10.1007/s00381-020-05012-8. Epub ahead of print. PMID: 33404721.
8)

Xiong Y, Yang L, Zhen W, Fangyong D, Feng W, Ting L. Conservative and surgical treatment of pediatric asymptomatic lumbosacral lipoma: a meta-analysis. Neurosurg Rev. 2016 Oct 28. [Epub ahead of print] Review. PubMed PMID: 27796602.
9)

Nejat A, Habibi Z, Nejat F. Lumbosacral Lipomyelomeningocele with Lateral Attachment to Neural Placode: Case Illustration. Pediatr Neurosurg. 2021 Mar 29:1-3. doi: 10.1159/000513409. Epub ahead of print. PMID: 33780945.
10)

Sarmento-Gonçalves I, Cunha M, Loureiro T, Pinto PS, Ramalho C. Fetal lipomyelomeningocele: A closed neural tube defect diagnosed at second trimester ultrasound examination. J Clin Ultrasound. 2018 Nov 8. doi: 10.1002/jcu.22662. [Epub ahead of print] PubMed PMID: 30411358.
11)

Wilkes SL, Choi JJ, Rooks VJ. Lumbosacral lipomyelomeningocele with anomalous osseous limb in a 3-month-old female. Radiol Case Rep. 2015 Dec 3;10(1):1051. doi: 10.2484/rcr.v10i1.1051. PMID: 27408662; PMCID: PMC4921161.
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