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Update: Atorvastatin for chronic subdural hematoma

Atorvastatin for chronic subdural hematoma

It is well known that inflammation influence chronic subdural hematoma (CSDH) formation to a large extent. Atorvastatin has pleiotropic effects on restraining inflammation and promoting angiogenesis besides its cholesterol-lowering function. Hence, atorvastatin may induce anti-inflammation effects and facilitate therapeutic effects for subdural hematoma (SDH).

Atorvastatin treatment may eliminate SDH and improve the neural function of the rats through its anti-inflammatory effects. Hence, it indicated that statin induced inflammatory modulation might play a significant role in rats 1).


Results of a preliminary prospective study showed that oral administration of atorvastatin is safe and effective in treating CSDH, offering a cost-effective alternative to surgery. A prospective randomized clinical trial is required to validate the effect of atorvastatin 2). 3).


Jiang et al. reported a clinical research trial protocol that was designed to evaluate the therapeutic effects of atorvastatin on CSDH 4).

Limited evidence suggests that oral atorvastatin may be beneficial in the management of CSDH. Further high-quality studies focused on dosage, duration, hematoma size are needed to further elucidate the role of atorvastatin in the management of CSDH 5).

A retrospective cohort comparison study has shown that CSDH with Atorvastatin had a lower rate of deterioration and burr-hole drainage 6).

The knowledge of the conservative treatment modalities for cSDH is sparse and based on small case series and low grade evidence. However, some treatment modalities seem promising even in symptomatic patients with large haematomas. Randomised controlled trials are currently underway, and will hopefully provide us with good evidence for or against the conservative treatment of cSDH 7).

Retracted articles

Atorvastatin administration may decrease the risks of recurrence.Patients with severe brain atrophy and bilateral CSDH are prone to the recurrence 8) is a retracted article 9).

Effect of atorvastatin on resolution of chronic subdural hematoma: a prospective observational study [RETRACTED] 10).

1)

Li T, Wang D, Tian Y, Yu H, Wang Y, Quan W, Cui W, Zhou L, Chen J, Jiang R, Zhang J. Effects of atorvastatin on the inflammation regulation and elimination of subdural hematoma in rats. J Neurol Sci. 2014 Jun 15;341(1-2):88-96. doi: 10.1016/j.jns.2014.04.009. Epub 2014 Apr 13. PubMed PMID: 24774750.
2)

Wang D, Li T, Tian Y, Wang S, Jin C, Wei H, Quan W, Wang J, Chen J, Dong J, Jiang R, Zhang J. Effects of atorvastatin on chronic subdural hematoma: a preliminary report from three medical centers. J Neurol Sci. 2014 Jan 15;336(1-2):237-42. doi: 10.1016/j.jns.2013.11.005. Epub 2013 Nov 14. PubMed PMID: 24269089.
3)

Xu M, Chen P, Zhu X, Wang C, Shi X, Yu B. Effects of Atorvastatin on Conservative and Surgical Treatments of Chronic Subdural Hematoma in Patients. World Neurosurg. 2016 Jul;91:23-8. doi: 10.1016/j.wneu.2016.03.067. Epub 2016 Mar 29. PubMed PMID: 27044372.
4)

Jiang R, Wang D, Poon WS, Lu YC, Li XG, Zhao SG, Wang RZ, You C, Yuan XR, Zhang JM, Feng H, Fei Z, Yu XG, Zhao YL, Hu J, Kang DZ, Yu RT, Gao GD, Zhu XD, Sun T, Hao JH, Liu XZ, Su N, Yue SY, Zhang JN. Effect of ATorvastatin On Chronic subdural Hematoma (ATOCH): a study protocol for a randomized controlled trial. Trials. 2015 Nov 18;16:528. doi: 10.1186/s13063-015-1045-y. PubMed PMID: 26581842; PubMed Central PMCID: PMC4652431.
5)

Qiu S, Zhuo W, Sun C, Su Z, Yan A, Shen L. Effects of atorvastatin on chronic subdural hematoma: A systematic review. Medicine (Baltimore). 2017 Jun;96(26):e7290. doi: 10.1097/MD.0000000000007290. Review. PubMed PMID: 28658127; PubMed Central PMCID: PMC5500049.
6)

Chan DY, Chan DT, Sun TF, Ng SC, Wong GK, Poon WS. The use of atorvastatin for chronic subdural haematoma: a retrospective cohort comparison study(). Br J Neurosurg. 2017 Feb;31(1):72-77. doi: 10.1080/02688697.2016.1208806. Epub 2016 Nov 23. PubMed PMID: 27881024.
7)

Soleman J, Noccera F, Mariani L. The conservative and pharmacological management of chronic subdural haematoma. Swiss Med Wkly. 2017 Jan 19;147:w14398. doi: smw.2017.14398. PubMed PMID: 28102879.
8)

Liu H, Luo Z, Liu Z, Yang J, Kan S. Atorvastatin May Attenuate Recurrence of Chronic Subdural Hematoma. Front Neurosci. 2016 Jun 28;10:303. doi: 10.3389/fnins.2016.00303. eCollection 2016. Retraction in: Front Neurosci. 2016 Oct 07;10 :465. PubMed PMID: 27445673; PubMed Central PMCID: PMC4923224.
9)

Frontiers Editorial Office. Retraction: Atorvastatin May Attenuate Recurrence of Chronic Subdural Hematoma. Front Neurosci. 2016 Oct 7;10:465. eCollection 2016. PubMed PMID: 27738420; PubMed Central PMCID: PMC5054353.
10)

Liu H, Liu Z, Liu Y, Kan S, Yang J, Liu H. Effect of atorvastatin on resolution of chronic subdural hematoma: a prospective observational study [RETRACTED]. J Neurosurg. 2016 Jul 29:1-10. doi: 10.3171/2015.12.JNS151991. [Epub ahead of print] Retraction in: J Neurosurg. 2017 Feb;126(2):651. PubMed PMID: 27471887.

Update: Cerebellopontine angle arachnoid cyst

Cerebellopontine angle arachnoid cyst

Epidemiology

Middle cranial fossa is the most common site of intracranial arachnoid cysts, followed by the cerebellopontine angle (CPA) and suprasellar area.

Clinical features

They usually remain asymptomatic so they are often diagnosed incidentally during radiological evaluation for other reason 1).

As these cysts enlarge, they may compress surrounding structures and cause neurological symptoms. Patients may present with vague, nonspecific symptoms such as headache and ataxia2).

These cysts also can cause dysfunction of specific cranial nerves, including III, IV, VI (to cause diplopia), V (to induce trigeminal neuralgia), VII (to cause congenital or acquired facial paralysis), VIII (to cause hearing loss, tinnitus, vertigo), X (to result in hoarseness and dysphagia) 3) 4) 5).

Gurkas et al. report a patient with cranial nerve palsies and mirror movements found in upper extremities. They postulated that CPA arachnoid cyst compressing the brain stem and the pyramidal decussation may lead to mirror movements 6).

Diagnosis

MRI (magnetic resonance imaging) scan techniques have led to CPA arachnoid cysts being more frequently diagnosed and with a higher degree of certainty. The need for further understanding of their natural history as well as for the development of a management rationale has been highlighted with this increased rate of diagnosis.

In the series of Alaani et al. these lesions have a characteristic location in the posterior-inferior aspect of the CPA below the facial and vestibulocochlear nerves. These cysts did not show change in size on repeated MRI scan and the patients’ symptoms did not progress over the period of follow up 7).

Differential diagnosis

The differential diagnosis of an arachnoid cyst of the cerebellopontine angle includes other cystic lesions (epidermoid and neurenteric cyst, cystic acoustic schwannoma).

MRI is helpful in differentiating arachnoid cysts from those cystic lesions. If a pathologic cause of a retrocochlear disorder is suspected in a patient with a unilateral sensorineural hearing loss and tinnitus, MRI should be performed to evaluate the cerebellopontine angle.

On MRI, arachnoid cysts appear as smooth-surfaced lesions that in all magnetic resonance sequences exhibit a signal characteristic of CSF. In contrast, epidermoid cysts show mixed signals on FLAIR images and high signals on diffusion weighted images. Neurenteric cysts present high signals on T1-weighted images and cystic schwannomas show some foci of contrast enhancement on T1-weighted postcontrast images 8) 9).

Treatment

The optimal surgical management of arachnoid cysts remains controversial.

Although surgery for these entities is controversial, arachnoid cysts can be treated surgically with open craniotomy for cyst removal, fenestration into adjacent arachnoid spaces, shunting of cyst contents, or endoscopic fenestration.

Alaani et al. support a conservative management approach to the majority of these cysts 10).

The definitive treatment for these arachnoid cysts is a retrosigmoid suboccipital craniotomy and microsurgical resection and fenestration of the cyst walls 11).

Outcome

The risks of surgery are few, but complications (meningitis, hemiparesis, oculomotor palsy, subdural hematoma, grand mal epilepsy, and death) have been reported 12)13) 14).

Olaya et al. report the first case of complete recovery from sensorineural hearing loss and facial weakness following endoscopic fenestration 15).

Case series

2017

3 pediatric patients with CPA arachnoid cysts (2 with hearing loss and 1 with recurrent headaches) who underwent neurosurgical treatment at the authors’ institution.

Four pediatric patients were diagnosed with CPA arachnoid cysts at the International Neuroscience Institute during the period from October 2004 through August 2012, and 3 of these patients underwent surgical treatment. The authors describe the patients’ clinical symptoms, the surgical approach, and the results on long-term follow-up. RESULTS One patient (age 14 years) who presented with headache (without hearing deficit) became asymptomatic after surgical treatment. The other 2 patients who underwent surgical treatment both had hearing loss. One of these children (age 9 years) had recent-onset hypacusia and experienced complete recovery immediately after the surgery. The other (age 6 years) had a longer history (2 years) of progressive hearing loss and showed an interruption of the deficit progression and only mild improvement at the follow-up visit.

CPA arachnoid cysts are uncommon in pediatric patients. The indication and timing of the surgical treatment are fundamental, especially when a hearing deficit is present 16).

2005

Alaani et al. present a series of five adult patients with different clinical presentations attributed to CPA arachnoid cysts. These lesions have a characteristic location in the posterior-inferior aspect of the CPA below the facial and vestibulocochlear nerves. These cysts did not show change in size on repeated MRI scan and the patients’ symptoms did not progress over the period of follow up. The findings would support a conservative management approach to the majority of these cysts 17).

1997

Five patients (three male and two female patients) with a mean age of 5.6 years have been operated on at the Department of Neurosurgery, New York University Medical Center, USA. since 1980 till 1997.

All five arachnoid cysts compressed the cerebellum or brain stem. One patient had associated hydrocephalus. Three patients presented with refractory headaches associated with nausea and vomiting. The remaining two patients presented with cerebellar signs. No patient had an initial cranial neuropathy.

All patients underwent a retrosigmoid suboccipital craniotomy and microsurgical resection and fenestration of the cyst walls. One patient underwent two procedures. A cystoperitoneal shunt was inserted at the first operation. After the shunting procedure, the patient’s condition deteriorated; however, after the microsurgical resection and fenestration, his symptoms improved. With a mean 5.2-year follow-up, there has been no evidence of clinical or radiographic recurrence 18).

Case reports

2017

A 4-year-old boy with global developmental delay, esotropia, moderate aortic root dilation, genu valgum, and in-toeing gait. MRI brain for evaluation of neonatal hypotonia revealed a left cerebellopontine angle arachnoid cyst. He referred on newborn hearing screening, and diagnostic auditory brainstem response (ABR) showed left profound retrocochlear hearing loss. Surgical intervention for the arachnoid cyst was deferred, with spontaneous resolution at age two years without hearing recovery. CMA revealed a novel, de novo 5.1 Mb microdeletion of 22q13.31q13.33 not involving SHANK3, a gene typically deleted in PMS.

As diagnostic sensitivity improves, smaller chromosomal imbalances will be detectable related to milder or different phenotypes. They present two patients with novel deletions of chromosome 22q13 associated with multiple congenital anomalies and features distinct from PMS 19).

2016

A 14-year-old previously healthy girl presented to our outpatient clinic with a 6-weeks history of frontal headache. They typically would start in the occipital region and then radiate bifrontally. The neurological examination was unremarkable. Magnetic resonance imaging revealed an extra-axial bilateral lesion in bilateral cerebellopontine angle, larger on left side. The lesions were homogeneously hypointenese on T1-weighted imaging and hyperintense on T2-weighted imaging without evidence of contrast enhancement and without evidence of restriction on diffusion-weighted imaging. No surgical treatment was indicated.

Bilateral arachnoid cysts of the cerebellopontine angle are very infrequent and the main indication for surgery is the existence of clinical symptoms or neurological deficit coincident with the locations of the cysts 20).

2015

Petscavage et al. present the case of a 49-year-old woman who presented with acute, nonprogressive left sensorineural hearing loss and benign positional vertigo that was associated with an arachnoid cyst of the cerebellopontine angle. The presence of the lesion was documented by MRI examinations that were obtained 7 years apart. Arachnoid cysts at the cerebellopontine angle are usually found incidentally on MRI performed for unrelated reasons. However, if the arachnoid cyst displaces or compresses adjacent cranial nerves, symptoms may result. They review the salient imaging features of arachnoid cysts that allow their differentiation from other lesions of the cerebellopontine angle 21).


Gurkas et al. report a patient with a CPA arachnoid cyst. He presented with cranial nerve palsies and mirror movements found in upper extremities. They postulated that CPA arachnoid cyst compressing the brain stem and the pyramidal decussation may lead to mirror movements, and conclude that mirror movements can be associated with CPA arachnoid cyst 22).


A 71-year old woman presenting with a right hemifacial spasm and an ipsilateral arachnoid cyst. Preoperative magnetic resonance imaging findings suggested a neurovascular compression caused by displacement of the facial-acoustic complex and the anterior inferior cerebellar artery by the cyst. Cyst excision and microvascular decompression of the facial nerve achieved permanent relief. The existing cases of arachnoid cysts causing hemifacial spasm are reviewed and the importance of a secondary neurovascular conflict identification and decompression in these cases is highlighted 23).


Trigeminal Neuralgia in a Child With a Cerebellopontine Angle Arachnoid Cyst 24).


Sharma et al. report two cases of bilateral CPA AC with their pathophysiology and review of literature 25).

2014

Visagan et al. first report a CPA arachnoid cyst causing TGN in a paediatric case 26).

2012

A 62-year-old man complaining of vertigo and progressive hearing loss was diagnosed with an arachnoid cyst at the right cerebellopontine angle based on magnetic resonance imaging (MRI). In this case-report, we used computed tomography (CT) cisternography to determine whether the arachnoid cyst communicated with the cerebrospinal fluid (CSF) space. Differentiating between a noncommunicating and communicating arachnoid cyst is required for presurgical evaluation. CT cisternography is a less used but reliable radiological technique for determining the presence of communication, and could therefore be included in the diagnostic work-up of arachnoid cysts. The patient underwent surgery with fenestration of the arachnoid cyst; his vertigo improved and his hearing was preserved 27).


Superior oblique myokymia (SOM) is a rare disorder with an unclear pathogenesis. We describe a first reported case of chronic disabling SOM in association with a cerebellopontine angle arachnoid cyst, who had a gradual and eventually complete symptomatic resolution 8 months following cyst marsupialisation. Among other aetiologies, SOM may therefore be due to abnormal CSF flow dynamics resulting in structural compromise of the nerve 28).

2011

A 7-month-old infant presented to the hospital with a history of delayed milestones and an abnormal increase in head circumference. Magnetic resonance images and CT scans of the brain showed a large CSF cavity involving the entire brainstem and a right CPA arachnoid cyst causing obstruction of the fourth ventricle and dilation of the lateral and third ventricles. Cerebrospinal fluid diversion was performed by direct communication from the syringobulbia cavity to the left lateral ventricle and from the left lateral ventricle through another ventricular catheter; external ventricular drainage was performed temporarily for 5 days. Communication between the syrinx and arachnoid cyst was confirmed. Clinically, there was a reduction in head circumference, and serial MR imaging of the brain showed a decrease in the size of the syrinx cavity and the ventricle along with opening of the normal CSF pathways. The postoperative course was uneventful, and no further intervention was necessary. On follow-up of the child at 3 years, his developmental milestones were normal. Surgical intervention for this condition is mandatory. The appropriate type of surgery should be performed on the basis of the pathophysiology of the developing syringobulbia 29).


A 47-year-old woman complaining of sharp and lancinating pain in the right periauricular and submandibular areas visited our hospital. Swallowing, chewing, and lying on her right side triggered the pain. Her neurologic examination revealed no specific abnormalities. The results of routine hematologic and blood chemistry studies were all within normal limits. Carbamazepine and gabapentin were given, but her symptoms persisted. Her pain was temporarily relieved only by narcotic pain medication. MRI showed an arachnoid cyst located in the right cerebellomedullary cistern extending to the cerebellopontine cistern. Cyst removal was performed via a right retrosigmoid approach. Lateral suboccipital craniotomy was performed using the right park-bench position. After opening the dura and cerebellopontine angle, the arachnoid cyst was exposed. The arachnoid cyst was compressing the flattened lower cranial nerves at the right jugular fossa. Her symptoms resolved postoperatively. Two months after the operation, she was completely free from her previous symptoms 30).

2009

A rare case of cerebellopontine angle arachnoid cyst manifesting as hemifacial spasm (HFS) is reported. The patient is a 42-year-old woman with 10-month history of left HFS. A preoperative magnetic resonance imaging scan showed a well-demarcated area, hypointense on T1-weighted imaging and hyperintense on T2-weighted imaging, in the left cerebellopontine angle, without contrast enhancement, resembling an arachnoid cyst. METHODS: The cyst was excised with microneurosurgical technique and the facial, vestibular, and acoustic nerves were completely decompressed from the arachnoid wall. RESULTS: The postoperative course was uneventful, and the left HFS disappeared immediately. Histologically, the cyst wall was a typical arachnoidal membrane. Ten months after surgery, the patient is symptom free. CONCLUSION: It is well-known that in approximately 10% of cases, trigeminal neuralgia can be caused by a space-occupying mass. However, the fact that HFS can also be caused by organic lesions as well as neurovascular compression is less well-known. Although the occurrence of tumor compression causing HFS has been previously recognized, cerebellopontine angle cysts have very rarely been described. The observation of a patient with a cerebellopontine angle arachnoid cyst causing HFS prompted us to review the literature relative to HFS caused by an organic lesion rather than neurovascular compression 31).

2007

a patient with a CPA arachnoid cyst who presented with hoarseness (unilateral vocal cord paralysis) and dysphagia secondary to isolated compression of the vagus nerve. This rare presentation of a CPA arachnoid cyst has not been reported previously. CLINICAL PRESENTATION: The patient described is a 50-year-old man who experienced a precipitous onset of hoarseness and dsyphagia. An otolaryngological evaluation revealed right-sided vocal cord paralysis. Brain magnetic resonance images displayed a cystic mass at the right CPA and anterior displacement of the vagus nerve. INTERVENTION: The patient underwent retrosigmoidal craniectomy with cyst fenestration, which was well tolerated. Intraoperatively, Cranial Nerve X was found splayed over the cyst and was consequently decompressed. CONCLUSION: Postoperatively, the patient’s dysphagia completely resolved. However, the results of a laryngeal electromyocardiogram revealed minimal evidence of recovery in the affected vocal fold, and the patient continued to suffer from dysphonia. Although CPA arachnoid cysts are rare, they should be considered when a patient presents with an isolated cranial nerve palsy. Treatment options include cyst fenestration and cranial nerve decompression 32).

2006

A 51 years old female is reported who was diagnosed by IRM of a 4,5 x 2 cm arachnoid cyst, situated on the left cerebello-pontine angle, with tinnitus, hearing loss and vertigo that mimicked a Meniere’s attack. We think thees benign tumors must be included in the differential diagnosis of Meniere’s disease because they can be indistinguishable from it clinically 33).

1)

Gönül E, Izci Y, Onguru O. Arachnoid cyst of the cerebellopontine angle associated with gliosis of the eighth cranial nerve. J Clin Neurosci. 2007 Jul;14(7):700-2. PubMed PMID: 17475499.
2) , 11) , 18)

Jallo GI, Woo HH, Meshki C, Epstein FJ, Wisoff JH. Arachnoid cysts of the cerebellopontine angle: diagnosis and surgery. Neurosurgery. 1997 Jan;40(1):31-7; discussion 37-8. Review. PubMed PMID: 8971821.
3)

Hayden MG, Tornabene SV, Nguyen A, Thekdi A, Alksne JF. Cerebellopontine angle cyst compressing the vagus nerve: Case report. Neurosurgery. 2007;60:E1150.
4)

Babu R, Murali R. Arachnoid cyst of the cerebellopontine angle manifesting as contralateral trigeminal neuralgia: Case report. Neurosurgery. 1991;28:886–7.
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Messerer M, Nouri M, Diabira S, Morandi X, Hamlat A. Hearing loss attributable to a cerebellopontine-angle arachnoid cyst in a child. Pediatr Neurosurg. 2009;45:214–9.
6) , 22)

Gurkas E, Altan BY, Gücüyener K, Kolsal E. Cerebellopontine angle arachnoid cyst associated with mirror movements. J Pediatr Neurosci. 2015 Oct-Dec;10(4):371-3. doi: 10.4103/1817-1745.174440. PubMed PMID: 26962347; PubMed Central PMCID: PMC4770653.
7) , 10) , 12) , 17)

Alaani A, Hogg R, Siddiq MA, Chavda SV, Irving RM. Cerebellopontine angle arachnoid cysts in adult patients: what is the appropriate management? J Laryngol Otol. 2005 May;119(5):337-41. PubMed PMID: 15949094.
8)

Brackmann DE, Arriaga MA: Extra-axial neoplasms of the posterior fossa. In: Cummings CW, Fredrickson JM, Harker LA, Krause CJ, Richardson MA, Schuller DE (eds) Otolaryngology Head and Neck Surgery. 3rd ed. St. Louis, MO: Mosby-Year Book: 1998: 3294-3314.
9)

Bonneville F, Sarrazin JL, Marsot-Dupuch K, Iffenecker C, Cordoliani YS, Doyon D, Bonneville JF: Unusual lesions of the cerebellopontine angle: a segmental approach. Radiographics 2001; 21: 419-43.
13)

Ucar T, Akyuz M, Kazan S, Tuncer R: Bilateral cerebellopontine angle arachnoid cysts: case report. Neurosurgery 2000; 47: 966-968.
14)

Eslick GD, Chalasani V, Seex K: Diplopia and headaches associated with cerebellopontine angle arachnoid cyst. ANZ J Surg 2002; 72: 915-917.
15)

Olaya JE, Ghostine M, Rowe M, Zouros A. Endoscopic fenestration of a cerebellopontine angle arachnoid cyst resulting in complete recovery from sensorineural hearing loss and facial nerve palsy. J Neurosurg Pediatr. 2011 Feb;7(2):157-60. doi: 10.3171/2010.11.PEDS10281. PubMed PMID: 21284461.
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Giordano M, Gallieni M, Samii A, Di Rocco C, Samii M. Surgical management of cerebellopontine angle arachnoid cysts associated with hearing deficit in pediatric patients. J Neurosurg Pediatr. 2017 Nov 24:1-5. doi: 10.3171/2017.8.PEDS17341. [Epub ahead of print] PubMed PMID: 29171799.
19)

Ha JF, Ahmad A, Lesperance MM. Clinical characterization of novel chromosome 22q13 microdeletions. Int J Pediatr Otorhinolaryngol. 2017 Apr;95:121-126. doi: 10.1016/j.ijporl.2016.12.008. Epub 2016 Dec 23. PubMed PMID: 28576520.
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Gelabert-Gonzalez M, Aran-Echabe E, Pita-Buezas L. [Bilateral cerebellopontine arachnoid cyst]. Rev Neurol. 2016 Jun 16;62(12):555-8. Spanish. PubMed PMID: 27270677.
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Petscavage JM, Fink JR, Chew FS. Acute sensorineural hearing loss resulting from cerebellopontine angle arachnoid cyst. Radiol Case Rep. 2015 Nov 6;5(2):435. doi: 10.2484/rcr.v5i2.435. PubMed PMID: 27307864; PubMed Central PMCID: PMC4898228.
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Ruiz-Juretschke F, Vargas A, González-Rodrigalvarez R, Garcia-Leal R. Hemifacial spasm caused by a cerebellopontine angle arachnoid cyst. Case report and literature review. Neurocirugia (Astur). 2015 Nov-Dec;26(6):307-10. doi: 10.1016/j.neucir.2015.05.001. Review. PubMed PMID: 26165486.
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Grande-Martín A, Díaz-Conejo R, Verdú-Pérez A, Hernández-Moneo JL. Trigeminal Neuralgia in a Child With a Cerebellopontine Angle Arachnoid Cyst. Pediatr Neurol. 2015 Aug;53(2):178-9. doi: 10.1016/j.pediatrneurol.2015.03.010. PubMed PMID: 25937388.
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Sharma A, Sharma A, Mittal RS, Gandhi A. Bilateral cerebellopontine arachnoid cyst: A rare entity. Br J Neurosurg. 2015;29(4):576-8. doi: 10.3109/02688697.2015.1015100. PubMed PMID: 25815737.
26)

Visagan R, Wright D, Jayamohan J. Trigeminal neuralgia in a paediatric patient caused by arachnoid cyst. Br J Neurosurg. 2014 Sep 15:1-2. [Epub ahead of print] PubMed PMID: 25222867.
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Abhinav K, Park ND, Patel NK. Trochlear myokymia secondary to cerebellopontine angle arachnoid cyst. Br J Neurosurg. 2012 Oct;26(5):754-5. doi: 10.3109/02688697.2011.641617. PubMed PMID: 22324436.
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Muroi A, Syms NP, Oi S. Giant syringobulbia associated with cerebellopontine angle arachnoid cyst and hydrocephalus. J Neurosurg Pediatr. 2011 Jul;8(1):30-4. doi: 10.3171/2011.4.PEDS10565. PubMed PMID: 21721885.
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32)

Hayden MG, Tornabene SV, Nguyen A, Thekdi A, Alksne JF. Cerebellopontine angle cyst compressing the vagus nerve: case report. Neurosurgery. 2007 Jun;60(6):E1150; discussion 1150. PubMed PMID: 17538363.
33)

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Update: Familial cerebral cavernous malformation

Familial cerebral cavernous malformation

Familial cerebral cavernous malformations, which account for at least 20% of all cases, can be passed from parent to child. Individuals with familial CCMs typically have multiple lesions. Familial CCMs are passed through families in an autosomal dominant manner, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Each child of an individual with familial CCM has a 50% chance of inheriting the mutation.

It is an autosomal-dominant disease with incomplete penetrance. The pathogenic genes of FCCM have been mapped into three loci: CCM1/KRIT1, CCM2/MGC4607, and CCM3/PDCD10.

see https://www.ncbi.nlm.nih.gov/books/NBK1293/.


Although the clinical course is unpredictable, symptoms typically present during adult life and include headaches, focal neurological deficits, seizures, and potentially fatal stroke. In addition to neural lesions, extraneural cavernous malformations have been described in familial disease in several tissues, in particular the skin 1).


In recent years there has been an increasing amount of publications linking FCCMs with other pathology, predominantly with extracranial and intracranial mesenchymal anomalies.

When faced with an unusual clinical feature in a patient with a Mendelian disorder, the clinician may entertain the possibilities of either the feature representing a novel manifestation of that disorder or the co-existence of a different inherited condition. Here we describe an individual with a submandibular oncocytoma, pulmonary bullae and renal cysts as well as multiple cerebral cavernous malformations and haemangiomas. Genetic investigations revealed constitutional mutations in FLCN, associated with Birt-Hogg-Dubé syndrome (BHD) and CCM2, associated with familial cerebral cavernous malformation. Intracranial vascular pathologies (but not cerebral cavernous malformation) have recently been described in a number of individuals with BHD (Kapoor et al. in Fam Cancer 14:595-597, 10.1007/s10689-015-9807-y , 2015) but it is not yet clear whether they represent a genuine part of that conditions’ phenotypic spectrum. We suggest that in such instances of potentially novel clinical features, more extensive genetic testing to consider co-existing conditions should be considered where available. The increased use of next generation sequencing applications in diagnostic settings is likely to lead more cases such as this being revealed 2).


A study described an unusual association between 2 independent hereditary diseases of confirmed genetic origin-a combination that has not been described previously 3).

Rosário Marques et al. documented a novel mutation on KRIT1 gene, and the second to be reported in a Portuguese family. This mutation consists in a two nucleotide insertion (c.947_948insAC) within the exon 10, resulting in premature protein termination (p.Leu317Argfs*2). These findings will hopefully contribute to a better clinical, imaging and genetic characterisation of this disease, particularly while trying to identify the factors that influence its treatment and prognosis 4).


Yang et al., investigated the genetic mutation in a Chinese family with FCCM.

The proband is a 29-year-old female presenting with a 1-month history of headache. Brain magnetic resonance imaging (MRI) revealed multiple intracranial lesions, the largest one showing a popcorn-like appearance. After a 4-year conservative observation, there was no significant clinical or radiological progression. Family investigation found five of her relatives had multiple CCM lesions. DNA sequencing analysis in the proband disclosed a novel heterozygous deletion mutation (c.1919delT; p.Phe640SerfsX21) in exon 17 of the CCM1/KRIT1 gene. This mutation leads to a frameshift and is predicted to cause a premature termination codon to generate a truncated Krev interaction trapped-1 (Krit1) protein of 659 amino acids. The mutation segregated with the disease in the family. C The current study identified a novel CCM1/KRIT1 heterozygous deletion mutation (c.1919delT) associated with FCCM. The findings expand the CCM gene mutation profiles in the Chinese population, which will be beneficial for genetic counseling 5).


A proband was hospitalized for sudden unconsciousness and underwent surgical treatment. The section of lesions showed classical cavernous-dilated vessels without intervening brain parenchyma, and hemosiderin-laden macrophages were accumulated in the surrounding tissue. In addition, magnetic resonance imaging (MRI) showed severe multiple cerebral cavernous malformation (CCM) lesions in cerebrum, brainstem, and cerebellum in other affected subjects. Especially, for the proband’s mother, hundreds of lesions were presented, and a few lesions were found in the expanded lateral ventricle (Evans’ index =0.33). Moreover, she showed the similar symptoms of hydrocephalus, including headache, dizziness, and diplopia. It was extremely rare in previous reports. To date, the genetic alterations leading to FCCM in Chinese population remain largely unknown. We investigated genetic defects of this family. Sequence analyses disclosed a novel heterozygous insertion mutation (c.1896_1897insT; p.Pro633SerfsTer22) in KRIT1/CCM1. Moreover, our real-time PCR results revealed that the mRNA level of KRIT1/CCM1 were significantly decreased in FCCM subjects (CCM family =0.42 ± 0.20 vs. healthy control =1.01 ± 0.16, P = 0.004). It indicated that this mutation could cause KRIT1/CCM1 functional mRNA deficiency. It may be closely related with the pathogenesis of FCCM. Our findings provided a new gene mutation profile which will be of great significance in early diagnosis and appropriate clinical surveillance of FCCM patients 6).

Case series

Fifty-seven familial CCM type-1 patients were included in this institutional review board-approved study. Baseline SWI (n = 57) and follow-up SWI (n = 17) were performed on a 3T Siemens MR scanner with lesions counted manually by the study neuroradiologist. We modified an algorithm for detecting radiation-induced microbleeds on SWI images in brain tumor patients, using a training set of 22 manually delineated CCM microbleeds from two random scans. Manual and automated counts were compared using linear regression with robust standard errors, intra-class correlation (ICC), and paired t tests. A validation analysis comparing the automated counting algorithm and a consensus read from two neuroradiologists was used to calculate sensitivity, the proportion of microbleeds correctly identified by the automated algorithm. RESULTS: Automated and manual microbleed counts were in strong agreement in both baseline (ICC = 0.95, p < 0.001) and longitudinal (ICC = 0.88, p < 0.001) analyses, with no significant difference between average counts (baseline p = 0.11, longitudinal p = 0.29). In the validation analysis, the algorithm correctly identified 662 of 1325 microbleeds (sensitivity=50%), again with strong agreement between approaches (ICC = 0.77, p < 0.001). CONCLUSION: The automated algorithm is a consistent method for counting microbleeds in familial CCM patients that can facilitate lesion quantification and tracking 7).


The authors retrospectively reviewed abdominal CT scans in 38 patients with fCCM, 38 unaffected age- and sex-matched control subjects, and 13 patients with sporadic, nonfamilial cerebral cavernous malformation (CCM). The size, number, and laterality of calcifications and the morphologic characteristics of the adrenal gland were recorded. Brain lesion count was recorded from brain magnetic resonance (MR) imaging in patients with fCCM. The prevalence of adrenal calcifications in patients with fCCM was compared with that in unaffected control subjects and those with sporadic CCM by using the Fisher exact test. Additional analyses were performed to determine whether age and brain lesion count were associated with adrenal findings in patients with fCCM. Results Small focal calcifications (SFCs) (≤5 mm) were seen in one or both adrenal glands in 19 of the 38 patients with fCCM (50%), compared with 0 of the 38 unaffected control subjects (P < .001) and 0 of the 13 subjects with sporadic CCM (P = .001). Adrenal calcifications in patients with fCCM were more frequently left sided, with 17 of 19 patients having more SFCs in the left adrenal gland than the right adrenal gland and 50 of the 61 observed SFCs (82%) found in the left adrenal gland. No subjects had SFCs on the right side only. In patients with fCCM, the presence of SFCs showed a positive correlation with age (P < .001) and number of brain lesions (P < .001). Conclusion Adrenal calcifications identified on CT scans are common in patients with fCCM and may be a clinically silent manifestation of disease 8).

1)

de Vos IJ, Vreeburg M, Koek GH, van Steensel MA. Review of familial cerebral cavernous malformations and report of seven additional families. Am J Med Genet A. 2017 Feb;173(2):338-351. doi: 10.1002/ajmg.a.38028. Epub 2016 Oct 28. Review. PubMed PMID: 27792856.
2)

Whitworth J, Stausbøl-Grøn B, Skytte AB. Genetically diagnosed Birt-Hogg-Dubé syndrome and familial cerebral cavernous malformations in the same individual: a case report. Fam Cancer. 2017 Jan;16(1):139-142. doi: 10.1007/s10689-016-9928-y. PubMed PMID: 27722904; PubMed Central PMCID: PMC5243871.
3)

Belousova OB, Okishev DN, Ignatova TM, Balashova MS, Boulygina ES. Hereditary Multiple Cerebral Cavernous Malformations Associated with Wilson Disease and Multiple Lipomatosis. World Neurosurg. 2017 Sep;105:1034.e1-1034.e6. doi: 10.1016/j.wneu.2017.06.002. Epub 2017 Jun 8. PubMed PMID: 28602929.
4)

Rosário Marques I, Antunes F, Ferreira N, Grunho M. Familial cerebral cavernous malformation: Report of a novel KRIT1 mutation in a Portuguese family. Seizure. 2017 Nov 10;53:72-74. doi: 10.1016/j.seizure.2017.10.020. [Epub ahead of print] PubMed PMID: 29145060.
5)

Yang C, Wu B, Zhong H, Li Y, Zheng X, Xu Y. A novel CCM1/KRIT1 heterozygous deletion mutation (c.1919delT) in a Chinese family with familial cerebral cavernous malformation. Clin Neurol Neurosurg. 2017 Nov 20;164:44-46. doi: 10.1016/j.clineuro.2017.11.005. [Epub ahead of print] PubMed PMID: 29169046.
6)

Wang H, Pan Y, Zhang Z, Li X, Xu Z, Suo Y, Li W, Wang Y. A Novel KRIT1/CCM1 Gene Insertion Mutation Associated with Cerebral Cavernous Malformations in a Chinese Family. J Mol Neurosci. 2017 Feb;61(2):221-226. doi: 10.1007/s12031-017-0881-5. Epub 2017 Feb 3. PubMed PMID: 28160210.
7)

Zou X, Hart BL, Mabray M, Bartlett MR, Bian W, Nelson J, Morrison LA, McCulloch CE, Hess CP, Lupo JM, Kim H. Automated algorithm for counting microbleeds in patients with familial cerebral cavernous malformations. Neuroradiology. 2017 Jul;59(7):685-690. doi: 10.1007/s00234-017-1845-8. Epub 2017 May 22. PubMed PMID: 28534135; PubMed Central PMCID: PMC5501247.
8)

Strickland CD, Eberhardt SC, Bartlett MR, Nelson J, Kim H, Morrison LA, Hart BL. Familial Cerebral Cavernous Malformations Are Associated with Adrenal Calcifications on CT Scans: An Imaging Biomarker for a Hereditary Cerebrovascular Condition. Radiology. 2017 Aug;284(2):443-450. doi: 10.1148/radiol.2017161127. Epub 2017 Mar 20. PubMed PMID: 28318403; PubMed Central PMCID: PMC5519414.

Update: GLARIUS trial

GLARIUS trial

The GLARIUS trial which investigated the efficacy of bevacizumab (BEV)/irinotecan (IRI) as compared to standard temozolomide (TMZ) in the first-line therapy of MGMT promoter methylation glioblastoma showed that progression free survival was significantly prolonged by BEV/IRI while overall survival was similar in both arms 1).


A report focusses on quality of life (QoL) and Karnofsky performance score (KPS) during the whole course of the disease.

Patients (n=170) received standard radiotherapy and were randomized (2:1) for BEV/IRI or standard TMZ. At least every three months KPS was determined and QoL was measured using the EORTC QLQ-C30 and EORTC QLQ-BN20 questionnaires. A generalized estimating equation model (GEE) evaluated differences in the course of QoL and KPS over time. Also, the time to first deterioration and the time to postprogression deterioration was analyzed separately.

In all dimensions of QoL and KPS, GEE analyses and time to first deterioration analyses did not detect significant differences between the treatment arms. At progression, 82% of patients receiving second-line therapy in the standard arm received BEV second-line therapy. For the dimensions motor dysfunction and headaches, time to postprogression deterioration was prolonged in the standard arm receiving crossover second-line BEV in the vast majority of patients at the time of evaluation.

GLARIUS did not find indications for a BEV-induced detrimental effect on QoL in first-line therapy of MGMT-nonmethylated GBM patients. Moreover, GLARIUS provided some indirect corroborative data supporting the notion that BEV may have beneficial effects upon QoL in relapsed GBM 2).

1)

Herrlinger U, Schäfer N, Steinbach JP, Weyerbrock A, Hau P, Goldbrunner R, Friedrich F, Rohde V, Ringel F, Schlegel U, Sabel M, Ronellenfitsch MW, Uhl M, Maciaczyk J, Grau S, Schnell O, Hänel M, Krex D, Vajkoczy P, Gerlach R, Kortmann RD, Mehdorn M, Tüttenberg J, Mayer-Steinacker R, Fietkau R, Brehmer S, Mack F, Stuplich M, Kebir S, Kohnen R, Dunkl E, Leutgeb B, Proescholdt M, Pietsch T, Urbach H, Belka C, Stummer W, Glas M. Bevacizumab Plus Irinotecan Versus Temozolomide in Newly Diagnosed O6-Methylguanine-DNA Methyltransferase Nonmethylated Glioblastoma: The Randomized GLARIUS Trial. J Clin Oncol. 2016 May 10;34(14):1611-9. doi: 10.1200/JCO.2015.63.4691. Epub 2016 Mar 14. PubMed PMID: 26976423.

2)

Schäfer N, Proescholdt M, Steinbach JP, Weyerbrock A, Hau P, Grauer O, Goldbrunner R, Friedrich F, Rohde V, Ringel F, Schlegel U, Sabel M, Ronellenfitsch MW, Uhl M, Grau S, Hänel M, Schnell O, Krex D, Vajkoczy P, Tabatabai G, Mack F, Schaub C, Tzaridis T, Nießen M, Kebir S, Leutgeb B, Urbach H, Belka C, Stummer W, Glas M, Herrlinger U. Quality of life in the GLARIUS trial randomizing bevacizumab/irinotecan versus temozolomide in newly diagnosed, MGMT-nonmethylated glioblastoma. Neuro Oncol. 2017 Nov 7. doi: 10.1093/neuonc/nox204. [Epub ahead of print] PubMed PMID: 29121274.

Update: Trampoline injury

Trampoline injury

Trampolines were responsible for over 6,500 pediatric cervical spine injuries in 1998. This represents a five-fold increase in just 10 years. While most have been minor, paraplegiaquadriplegia and death are all reported.

Brown and Lee present 2 cases of trampoline-related cervical spine injury and review the relevant literature. Additionally, they examine the efforts made to reduce the incidence of trampoline injuries, and discuss why these have failed. They conclude that safety guidelines and warnings are inadequate. In addition, they support recommendations for a ban on the use of trampolines by children 1).

see Severe Trampoline Injuries: Incidence and Risk Factors in Children and Adolescents 2).

Case reports

A 4-year-old boy who presented with neck pain after falling off a trampoline. His neurological examination did not reveal any focal abnormalities, but radiographs were thought to be consistent with a right, C4-C5, unilateral, jumped facet.

Reduction attempts were made with Gardner-Wells tongs and traction. After failure to achieve adequate reduction, evaluations using two-dimensional computed tomography confirmed congenitally absent cervical pedicles. He was treated conservatively and experienced resolution of their presenting symptoms.

The congenital absence of a cervical pedicle is a rare entity that is frequently misdiagnosed. Diagnoses can be accurately confirmed with two-dimensional computed tomography. Conservative treatment resulted in successful management of this clinical entity 3).

1)

Brown PG, Lee M. Trampoline injuries of the cervical spine. Pediatr Neurosurg. 2000 Apr;32(4):170-5. Review. PubMed PMID: 10940766.
2)

Korhonen L, Salokorpi N, Suo-Palosaari M, Pesälä J, Serlo W, Sinikumpu JJ. Severe Trampoline Injuries: Incidence and Risk Factors in Children and Adolescents. Eur J Pediatr Surg. 2017 Nov 22. doi: 10.1055/s-0037-1608676. [Epub ahead of print] PubMed PMID: 29166677.
3)

Sheehan J, Kaptain G, Sheehan J, Jane J Sr. Congenital absence of a cervical pedicle: report of two cases and review of the literature. Neurosurgery. 2000 Dec;47(6):1439-42. Review. PubMed PMID: 11126916.

Update: Chronic subdural hematoma recurrence

Chronic subdural hematoma recurrence

Epidemiology

Recurrence rates after chronic subdural hematoma (CSDH) evacuation with any of actual techniques twist drill craniostomy (TDC), burr hole craniostomy, craniotomy range from 5% to 30%. 1)

Risk factors

In the series of Han et al. independent risk factors for recurrence were as follows: age > 75 years (HR 1.72, 95% CI 1.03-2.88; p = 0.039), obesity (body mass index ≥ 25.0 kg/m2), and a bilateral operation 2).

Chon et al. shown that postoperative midline shifting (≥5 mm), diabetes mellitus, preoperative seizure, preoperative width of hematoma (≥20 mm), and anticoagulant therapy were independent predictors of the recurrence of chronic subdural hematoma.

According to internal architecture of hematoma, the rate of recurrence was significantly lower in the homogeneous and the trabecular type than the laminar and separated type 3).

see Chronic subdural hematoma and anticoagulant therapy.


The recurrence rate of chronic subdural hematoma cSDH seems to be related to the excessive neoangiogenesis in the parietal membrane, which is mediated via vascular endothelial growth factor (VEGF). This is found to be elevated in the hematoma fluid and is dependent on eicosanoid/prostaglandin and thromboxane synthesis via cyclooxygenase-2 (COX-2).


Antiplatelet therapy

Antiplatelet therapy significantly influences the recurrence of CSDH 4).

Pneumocephalus

Remaining pneumocephalus is seen as an approved factor of recurrence 5) 6).

Septation

Jack et al.found a 12% reoperation rate. CSDH septation (seen on computed tomogram scan) was found to be an independent risk factor for recurrence requiring reoperation (p=0.04). Larger post-operative subdural haematoma volume was also significantly associated with requiring a second drainage procedure (p<0.001). Independent risk factors of larger post-operative haematoma volume included septations within a CSDH (p<0.01), increased pre-operative haematoma volume (p<0.01), and a greater amount of parenchymal atrophy (p=0.04). A simple scoring system for quantifying recurrence risk was created and validated based on patient age (< or ≥80 years), haematoma volume (< or ≥160cc), and presence of septations within the subdural collection (yes or no).

Septations within CSDHs are associated with larger post-operative residual haematoma collections requiring repeat drainage. When septations are clearly visible within a CSDH, craniotomy might be more suitable as a primary procedure as it allows greater access to a septated subdural collection. The proposed scoring system combining haematoma volume, age, and presence of septations might be useful in identifying patients at higher risk for recurrence 7).

Membranectomy

Opening the internal hematoma membrane does not alter the rate of patients requiring revision surgery and the number of patients showing a marked residual hematoma six weeks after evacuation of a CSDH 8).

In the study of Lee et al, an extended surgical approach with partial membranectomy has no advantages regarding the rate of reoperation and the outcome. As initial treatment, burr-hole drainage with irrigation of the hematoma cavity and closed-system drainage is recommended. Extended craniotomy with membranectomy is now reserved for instances of acute rebleeding with solid hematoma 9).

Diabetes

Surgeons should consider informing patients with diabetes mellitus that this comorbidity is associated with an increased likelihood of recurrence

10) 11) 12).


Balser et al. report 11% recurrence, which included individuals who recurred as late as 3 years after initial diagnosis 13).

Close imaging follow-up is important for CSDH patients for recurrence prediction. Using quantitative CT volumetric analysis, strong evidence was provided that changes in the residual fluid volume during the ‘self-resolution’ period can be used as significantly radiological predictors of recurrence 14).

A structural equation model showed a significant association between increased antiinflammatory activity in hematoma fluid samples and a lower risk of recurrence, but this relationship was not statistically significant in venous blood samples. Moreover, these findings indicate that anti-inflammatory activities in the hematoma may play a role in the risk of a recurrence of CSDH 15).

Irrigation with artificial cerebrospinal fluid (ACF) decreased the rate of CSDH recurrence 16).

Treatment

There is no definite operative procedure for patients with intractable chronic subdural hematoma (CSDH).

Most recurrent hematomas are managed successfully with burr hole craniostomies with postoperative closed-system drainage. Refractory hematomas may be managed with a variety of techniques, including craniotomy or subdural-peritoneal shunt placement 17).

Although many studies have reported risk factors or treatments in efforts to prevent recurrence, those have focused on single recurrence, and little cumulative data is available to analyze refractory CSDH.

Matsumoto et al. defined refractory CSDH as ≥2 recurrences, then analyzed and compared clinical factors between patients with single recurrence and those with refractory CSDH in a cohort study, to clarify whether patients with refractory CSDH experience different or more risk factors than patients with single recurrence, and whether burr-hole irrigation with closed-system drainage reduces refractory CSDH.

Seventy-five patients had at least one recurrence, with single recurrence in 62 patients and ≥2 recurrences in 13 patients. In comparing clinical characteristics, patients with refractory CSDH were significantly younger (P=0.04) and showed shorter interval to first recurrence (P<0.001). Organized CSDH was also significantly associated with refractory CSDH (P=0.02). Multivariate logistic regression analysis identified first recurrence interval <1 month (OR 6.66, P<0.001) and age <71 years (OR 4.16, P<0.001) as independent risk factors for refractory CSDH. On the other hand, burr-hole irrigation with closed-system drainage did not reduce refractory CSDH.

When patients with risk factors for refractory CSDH experience recurrence, alternative surgical procedures may be considered as the second surgery, because burr-hole irrigation with closed-system drainage did not reduce refractory CSDH 18).

Implantation of a reservoir 19) 20) 21).

Subdural-peritoneal shunt 22).

Middle meningeal artery embolization

Embolization of the MMA is effective for refractory CSDH or CSDH patients with a risk of recurrence, and is considered an effective therapeutic method to stop hematoma enlargement and promote resolution 23) 24) 25) 26) 27) 28).

A pilot study indicated that perioperative middle meningeal artery (MMA) embolization could be offered as the least invasive and most effectual means of treatment for resistant patients of CSDHs with 1 or more recurrences 29).

Chihara et al. have treated three cases of CSDH with MMA embolization to date, but there was a postoperative recurrence in one patient, which required a craniotomy for hematoma removal and capsulectomy. MMA embolization blocks the blood supply from the dura to the hematoma outer membrane in order to prevent recurrences of refractory CSDH. Histopathologic examination of the outer membrane of the hematoma excised during craniotomy showed foreign-body giant cells and neovascular proliferation associated with embolization. Because part of the hematoma was organized in this case, the CSDH did not resolve when the MMA was occluded, and the development of new collateral pathways in the hematoma outer membrane probably contributed to the recurrence. Therefore, in CSDH with some organized hematoma, MMA embolization may not be effective. Magnetic resonance imaging (MRI) should be performed in these patients before embolization 30).

Case series

2017

A retrospective analysis of 756 consecutive patients with CSDH who underwent bur hole surgery at the Hanyang University Medical Center (Seoul and Guri) between January 1, 2004, and December 31, 2014. During the 6-month follow-up, 104 patients (13.8%) with recurrence after surgery for CSDH were identified. Independent risk factors for recurrence were as follows: age > 75 years (HR 1.72, 95% CI 1.03-2.88; p = 0.039), obesity (body mass index ≥ 25.0 kg/m2), and a bilateral operation.

This study determined the risk factors for recurrence of CSDH and their effects on outcomes. Further studies are needed to account for these observations and to determine their underlying mechanisms 31).

2016

Chronic subdural hematomas (cSDHs) have shown an increasing incidence in an ageing population over the last 20 years, while unacceptable recurrence rates of up to 30 % persist. The chronic subdural hematoma recurrence rate seems to be related to the excessive neoangiogenesis in the parietal membrane, which is mediated via vascular endothelial growth factor (VEGF). This is found to be elevated in the haematoma fluid and is dependent on eicosanoid/prostaglandin and thromboxane synthesis via cyclooxygenase-2 (COX 2). With this investigator-initiated trial (IIT) it was thought to diminish the recurrence rate of operated-on cSDHs by administering a selective COX-2 inhibitor (Celecoxib) over 4 weeks’ time postoperatively in comparison to a control group.

The thesis of risk reduction of cSDH recurrence in COX-2-inhibited patients was to be determined in a prospective, randomised, two-armed, open phase-II/III study with inclusion of 180 patients over a 2-year time period in four German university hospitals. The treated- and untreated-patient data were to be analysed by Fisher’s exact test (significance level of alpha, 0.05 [two-sided]).

After screening of 246 patients from January 2009 to April 2010, the study had to be terminated prematurely as only 23 patients (9.3 %) could be enrolled because of on-going non-steroid anti-rheumatic (NSAR) drug treatment or contraindication to Celecoxib medication. In the study population, 13 patients were treated in the control group (six women, seven men; average age 66.8 years; one adverse event (AE)/serious adverse event (SAE) needing one re-operation because of progressive cSDH (7.7 %); ten patients were treated in the treatment group (one woman, nine men; average age 64.7 years; five AEs/SAEs needing two re-operations because of one progressive cSDH and one wound infection [20 %]). Significance levels are obsolete because of insufficient patient numbers.

The theoretical advantage of COX-2 inhibition in the recurrent cSDH could not be transferred into the treatment of German cSDH patients as 66.6 % of the patients showed strict contraindications for Celecoxib. Furthermore, 55 % of the patients were already treated with some kind of COX-2 inhibition and, nevertheless, developed cSDH. Thus, although conceptually appealing, an anti-angiogenic therapy with COX-2 inhibitors for cSDH could not be realised in this patient population due to the high prevalence of comorbidities excluding the administration of COX2 inhibitors 32).

2010

Recurrence rates after chronic subdural hematoma (CSDH) evacuation with any of actual techniques twist drill craniostomy (TDC), burr hole craniostomy, craniotomy range from 5% to 30%. Use of drain has improved recurrence rates when used with burr-hole craniostomy. Now, we analyze predictors of recurrence of TDC with drain.

Three hundred twelve consecutive patients with CSDH have been studied in a retrospective study. Operative technique in all patients consisted in TDC with drain. Data recorded included any associated comorbidity. Radiologic measures of the CSDH before and after the procedure were studied. Clinical evaluation included Modified Rankin Scale, Glasgow Coma Scale (GCS), and neurological deficits. Two groups were compared: recurrence group and nonrecurrence group. Follow-up was for at least 1 year.

Twelve percent experienced recurrence. Preoperative CSDH width, preoperative midline shift, postoperative midline width, postoperative CSDH width, and residual CSDH 1 month later were significantly associated with CSDH recurrence. The logistic regression model for the multivariate analysis revealed that postoperative midline shift and postoperative neurological deficit were significantly associated with CSDH recurrence. The duration of treatment with dexamethasone was found not to be related with recurrence. Mortality before hospital discharge was 1%. Hospital stay was 2.5 days.

TDC with drain has similar results in recurrence rates, morbidity, mortality, and outcome as other techniques as burr-hole craniostomy with drain. Preoperative and postoperative hematoma width and midline shift are independent predictors of recurrence. Brain re-expansion and time of drain maintenance are important factors related with recurrence of CSDH. Future CSDH reservoirs must avoid negative pressure and sudden pressure changes inside the whole closed drain system 33).

Case reports

2016

Mewada et al. report a case with right hemiparesis and aphasia 1 month after a fall from a bicycle. Computed tomography scan of the head showed left chronic subdural hematoma, which was evacuated by burr-hole drainage. The postoperative course was complicated by reaccumulation within short period of time. On superselective digital subtraction angiography of MMA, iatrogenic dAVF was found on left side. We embolized successfully it using n-butyl cyanoacrylate after a third irrigation. No reaccumulation found in the postoperative period or at last follow-up. They proposed a treatment protocol based on the own experience and literature review.

Refractory chronic subdural hematoma with reaccumulation within a short interval should be subjected to digital subtraction angiography of the MMA. Embolization of ipsilateral MMA is safe, effective, and a useful option for the treatment of iatrogenic dAVF and resolution of hematoma 34).


An 85-year-old male presented with left CSDH, which recurred five times. The hematoma was irrigated and drained through a left frontal burr hole during the first to third surgery and through a left parietal burr hole during the fourth and fifth surgery. The hematoma had no septation and was well-evacuated during each surgery. Antiplatelet therapy for preventing ischemic heart disease was stopped after the second surgery, the hematoma cavity was irrigated with artificial cerebrospinal fluid at the third surgery, and the direction of the drainage tube was changed to reduce the postoperative subdural air collection at the fourth surgery. However, none of these interventions was effective. He was successfully treated by fibrin glue injection into the hematoma cavity after the fifth surgery.

This procedure may be effective for refractory CSDH in elderly patients 35).


A 67-year-old man with dural arteriovenous fistula (AVF) presenting as a non-traumatic chronic subdural hematoma (CSDH). This previously healthy patient was hospitalized due to progressive headache with subacute onset. He underwent burr-hole surgery twice for evacuating the left CSDH that was thickest at the posterior temporal area. The operative procedure and finding was not extraordinary, but subdural hematoma slowly progressed for days following the revision surgery. After investigation by super-selective external carotid angiography, a dural AVF found near the transverse-sigmoid sinus was diagnosed. Dural AVF was completely occluded with trans-arterial injecting polyvinyl alchol particles into the petrosquamosal branch of the middle meningeal artery. The patient showed a good neurological outcome with no additional intervention. Brain surgeons have to consider the possibility of dural AVF and perform cerebral angiogram if necessary when they manage the cases that have a spontaneously occurred and repeatedly recurring CSDH 36).

2007

Spontaneous intracranial hypotension (SIH) is reported to cause chronic subdural hematoma (SDH), however diagnosis of SIH in patients with SDH is not always easy.

Takahashi et al. report a case of chronic SDH refractory to repeated drainage, which was attributed to SIH. A forty-five-year-old man who had been suffering from orthostatic headache for one month was admitted to our hospital presenting with unconsciousness and hemiparesis. CT on admission revealed a chronic subdural hematoma, which was successfully treated once with subdural drainage. However, the patient fell into unconscious again with recurrence of the hematoma within several days. After two more sessions of drainage, SIH due to cerebrospinal fluid leakage was diagnosed with spinal magnetic resonance imaging (MRI) and radionuclide cisternography. Spinal MRI demonstrated abnormal fluid accumulation in the thoracic epidural space, and the radionuclide cisternogram showed early excretion of tracer into urine as well as absence of intracranial tracer filling. After treatment with epidural blood patching, the hematoma rapidly disappeared and he was discharged without symptoms. In the treatment of chronic SDH, especially in young to middle aged patient without preceding trauma or hematological disorders, physicians should pay attention to underlying SIH to avoid multiple surgery. MRI of the spine as well as radionuclide cisternography is useful in evaluation of this condition 37).

1) , 33)

Escosa Baé M, Wessling H, Salca HC, de Las Heras Echeverría P. Use of twist-drill craniostomy with drain in evacuation of chronic subdural hematomas: independent predictors of recurrence. Acta Neurochir (Wien). 2011 May;153(5):1097-103. doi: 10.1007/s00701-010-0903-3. Epub 2010 Dec 31. PubMed PMID: 21193935.

2) , 31)

Han MH, Ryu JI, Kim CH, Kim JM, Cheong JH, Yi HJ. Predictive factors for recurrence and clinical outcomes in patients with chronic subdural hematoma. J Neurosurg. 2017 Nov;127(5):1117-1125. doi: 10.3171/2016.8.JNS16867. Epub 2016 Dec 16. PubMed PMID: 27982768.

3)

Chon KH, Lee JM, Koh EJ, Choi HY. Independent predictors for recurrence of chronic subdural hematoma. Acta Neurochir (Wien). 2012 Sep;154(9):1541-8. doi: 10.1007/s00701-012-1399-9. Epub 2012 Jun 1. PubMed PMID: 22653496.

4)

Wada M, Yamakami I, Higuchi Y, Tanaka M, Suda S, Ono J, Saeki N. Influence of antiplatelet therapy on postoperative recurrence of chronic subdural hematoma: a multicenter retrospective study in 719 patients. Clin Neurol Neurosurg. 2014 May;120:49-54. doi: 10.1016/j.clineuro.2014.02.007. Epub 2014 Feb 24. PubMed PMID: 24731576.

5)

Mori K, Maeda M (2001) Surgical treatment of chronic subdural hematoma in 500 consecutive cases: clinical characteristics, surgical outcome, complications, and recurrence rate. Neurol Med Chir (Tokyo) 41:371–381

6)

Stanišić M, Hald J, Rasmussen IA, Pripp AH, Ivanović J, Kolstad F, Sundseth J, Züchner M, Lindegaard KF (2013) Volume and densities of chronic subdural haematoma obtained from CT imaging as predictors of postoperative recurrence: a prospective study of 107 operated patients. Acta Neurochir 155:323–333

7)

Jack A, O’Kelly C, McDougall C, Max Findlay J. Predicting Recurrence after Chronic Subdural Haematoma Drainage. Can J Neurol Sci. 2015 Jan 5:1-6. [Epub ahead of print] PubMed PMID: 25557536.

8)

Unterhofer C, Freyschlag CF, Thomé C, Ortler M. Opening the Internal Hematoma Membrane does not Alter the Recurrence Rate of Chronic Subdural Hematomas – A Prospective Randomized Trial. World Neurosurg. 2016 May 2. pii: S1878-8750(16)30210-8. doi: 10.1016/j.wneu.2016.04.081. [Epub ahead of print] PubMed PMID: 27150644.

9)

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Update: Anterior cerebral artery infarct

Anterior cerebral artery infarct

Stroke in the anterior cerebral artery territory are much less common than either middle cerebral artery or posterior cerebral artery territory infarcts.

Epidemiology

ACA territory infarcts are rare, comprising ~2% of ischaemic strokes.

ACA territory infarcts are less common because if the A1 segment is occluded there is generally enough collateral flow via the contralateral A1 segment to supply the distal ACA territory.

Etiology

Embolic strokes (often with MCA involvement) are the most common cause.

Rarely, they are also seen as a complication of severe midline shift, where the ACA is occluded by mass effect or severe vasospasm.

An asymmetry of the A1 segment of the anterior cerebral artery (A1SA) was identified on digital subtraction angiography studies from 127 patients (21.4%) and was strongly associated with anterior communicating artery aneurysm (ACoAA) (p < 0.0001, OR 13.7). An A1SA independently correlated with the occurrence of ACA infarction in patients with ACoAA (p = 0.047) and in those without an ACoAA (p = 0.015). Among patients undergoing Anterior communicating artery aneurysm endovascular treatment, A1SA was independently associated with the severity of ACA infarction (p = 0.023) and unfavorable functional outcome (p = 0.045, OR = 2.4).

An A1SA is a common anatomical variation in SAH patients and is strongly associated with ACoAA. Moreover, the presence of A1SA independently increases the likelihood of ACA infarction. In SAH patients undergoing ACoAA coiling, A1SA carries the risk for severe ACA infarction and thus an unfavorable outcome. Clinical trial registration no.: DRKS00005486 (http://www.drks.de/) 1).

Clinical features

Diagnosis

The features are those of cerebral infarction in the anterior cerebral artery vascular territory:

Paramedian frontoparietal cerebral cortex

Anterior corpus callosum.

Anterior limb of the internal capsule.

Inferior portion of the Caudate nucleus head.

Differential diagnosis

Case series

Kumral et al. studied 48 consecutive patients who admitted to the stroke unit over a 6-year period.

They performed magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) in all patients, and Diffusion weighted magnetic resonance imaging (DWI) in 21. In the stroke registry, patients with ACA infarction represented 1.3% of 3705 patients with ischemic stroke. The main risk factors of ACA infarcts was hypertension in 58% of patients, diabetes mellitus in 29%, hypercholesterolemia in 25%, cigarette smoking in 19%, atrial fibrillation in 19%, and myocardial infarct in 6%. Presumed causes of ACA infarct were large-artery disease and cardioembolism in 13 patients each, small-artery disease (SAD) in the territory of Heubner’s artery in two and atherosclerosis of large-arteries (<50% stenosis) in 16. On clinico-radiologic analysis there were three main clinical patterns depending on lesion side; left-side infarction (30 patients) consisting of mutism, transcortical motor aphasia, and hemiparesis with lower limb predominance; right side infarction (16 patients) accompanied by acute confusional state, motor hemineglect and hemiparesis; bilateral infarction (two patients) presented with akinetic mutism, severe sphincter dysfunction, and dependent functional outcome. Our findings suggest that clinical and etiologic spectrum of ACA infarction may present similar features as that of middle cerebral artery infarction, but frontal dysfunctions and callosal syndromes can help to make a clinical differential diagnosis. Moreover, at the early phase of stroke, DWI is useful imaging method to locate and delineate the boundary of lesion in the territory of ACA 3).

1)

Jabbarli R, Reinhard M, Roelz R, Kaier K, Weyerbrock A, Taschner C, Scheiwe C, Shah M. Clinical relevance of anterior cerebral artery asymmetry in aneurysmal subarachnoid hemorrhage. J Neurosurg. 2017 Nov;127(5):1070-1076. doi: 10.3171/2016.9.JNS161706. Epub 2016 Dec 23. PubMed PMID: 28009232.
3)

Kumral E, Bayulkem G, Evyapan D, Yunten N. Spectrum of anterior cerebral artery territory infarction: clinical and MRI findings. Eur J Neurol. 2002 Nov;9(6):615-24. PubMed PMID: 12453077.