Endoscopic third ventriculostomy and choroid plexus cauterization

Endoscopic third ventriculostomy and choroid plexus cauterization

Endoscopic third ventriculostomy with choroid plexus cauterization (ETV/CPC) offers an alternative to shunt.


While ventriculoperitoneal shunt (VPS) insertion is the standard treatment for myelomeningocele-associated hydrocephalus (MAH), it can be complicated by shunt infection and shunt malfunction. As such, endoscopic third ventriculostomy (ETV), with or without choroid plexus coagulation (CPC), has been proposed as an alternative.

ETV+CPC was associated with a higher success rate than ETV alone for MAH in a meta-analysis of published studies. ETV, with or without CPC, was technically feasible and safe for this patient population 1).


In the twenty-first century, choroid plexus cauterization (CPC) in combination with endoscopic third ventriculostomy (ETV) has emerged as an effective treatment for some infants with hydrocephalus, leading to the favourable condition of ‘shunt independence‘.

Coulter et al. provide a narrative technical review considering the indications, procedural aspects, morbidity and its avoidance, postoperative care and follow-up. The CP has been the target of hydrocephalus treatment for more than a century. Early eminent neurosurgeons including Dandy, Putnam and Scarff performed CPC achieving generally poor results, and so the procedure fell out of favour. In recent years, the addition of CPC to ETV was one of the reasons greater ETV success rates were observed in Africa, compared to developed nations, and its popularity worldwide has since increased. Initial results indicate that when ETV/CPC is performed successfully, shunt independence is more likely than when ETV is undertaken alone. CPC is commonly performed using a flexible endoscope via septostomy and aims to maximally cauterize the CP. Success is more likely in infants aged >1 month, those with hydrocephalus secondary to myelomeningocele and aqueductal obstruction and those with >90% cauterized CP. Failure is more likely in those with post-haemorrhagic hydrocephalus of prematurity (PHHP), particularly those <1 month of corrected age and those with prepontine scarring. High-quality evidence comparing the efficacy of ETV/CPC with shunting is emerging, with data from ongoing and future trials offering additional promise to enhance our understanding of the true utility of ETV/CPC 2).


In the quest to identify the optimal means of cerebrospinal fluid diversion free of shunt dependency, endoscopic third ventriculostomy (ETV) with choroid plexus cauterization (CPC) has been proposed as a promising procedure in select children. Supplementing traditional ETV with obliteration of the choroid plexus has been shown to decrease the likelihood of ultimate shunt dependency by roughly 20%. Originally devised to treat hydrocephalus in infants in sub-Saharan Africa, ETV/CPC has gained eager attention and cautious support in the developed world 3).

Diagnosing treatment failure is dependent on infantile hydrocephalus metrics, including head circumference, fontanel quality, and ventricle size.

Systematic review was performed using four electronic databases and bibliographies of relevant articles, with no language or date restrictions. Cohort studies of participants undergoing ETV/CPC that reported outcome were included using MOOSE guidelines. The outcome was time to repeat CSF diversion or death. Forest plots were created for pooled mean and its 95 % CI of outcome and morbidity.

Of 78 citations, 11 retrospective reviews (with 524 total participants) were eligible. Efficacy was achieved in 63 % participants at follow-up periods between 6 months and 8 years. Adverse events and mortality was reported in 3.7 and 0.4 % of participants, respectively. Publication bias was detected with respect to efficacy and morbidity of the procedure. A large discrepancy in success was identified between ETV/CPC in six studies from sub-Saharan Africa (71 %), compared to three studies from North America (49 %).

The reported success of ETV/CPC for infantile hydrocephalus is higher in sub-Saharan Africa than developed nations. Large long-term prospective multi-center observational studies addressing patient-important outcomes are required to further evaluate the efficacy and safety of this re-emerging procedure 4).

2016

It is not clear to what degree these metrics should be expected to change after ETV/CPC. Using these clinical metrics, Dewan et al., present and analyze the decision making in cases of ETV/CPC failure.

Infantile hydrocephalus metrics, including bulging fontanel, head circumference z-score, and frontal and occipital horn ratio (FOHR), were compared between ETV/CPC failures and successes. Treatment outcome predictive values of metrics individually and in combination were calculated.

Forty-four patients (57% males, median age 1.2 months) underwent ETV/CPC for hydrocephalus; of these patients, 25 (57%) experienced failure at a median time of 51 days postoperatively. Patients experiencing failure were younger than those experiencing successful treatment (0.8 vs 3.9 months, p = 0.01). During outpatient follow-up, bulging anterior fontanel, progressive macrocephaly, and enlarging ventricles each demonstrated a positive predictive value (PPV) of no less than 71%, but a bulging anterior fontanel remained the most predictive indicator of ETV/CPC failure, with a PPV of 100%, negative predictive value of 73%, and sensitivity of 72%. The highest PPVs and specificities existed when the clinical metrics were present in combination, although sensitivities decreased expectedly. Only 48% of failures were diagnosed on the basis all 3 hydrocephalus metrics, while only 37% of successes were negative for all 3 metrics. In the remaining 57% of patients, a diagnosis of success or failure was made in the presence of discordant data.

Successful ETV/CPC for infantile hydrocephalus was evaluated in relation to fontanel status, head growth, and change in ventricular size. In most patients, a designation of failure or success was made in the setting of discordant data 5).

2014

A study retrospectively reviewed medical records of 27 premature infants with intraventricular hemorrhage (IVH) and hydrocephalus treated with ETV and CPC from 2008 to 2011. All patients were evaluated using MRI before the procedure to verify the anatomical feasibility of ETV/CPC. Endoscopic treatment included third ventriculostomy, septostomy, and bilateral CPC. After ETV/CPC, all patients underwent follow-up for a period of 6-40 months (mean 16.2 months). The procedure was considered a failure if the patient subsequently required a shunt. The following factors were analyzed to determine a relationship to patient outcomes: gestational age at birth, corrected age and weight at surgery, timing of surgery after birth, grade of IVH, the status of the prepontine cistern and cerebral aqueduct on MRI, need for a ventricular access device prior to the endoscopic procedure, and scarring of the prepontine cistern noted at surgery.

Seventeen (63%) of 27 patients required a shunt after ETV/CPC, and 10 patients did not require further CSF diversion. Several factors studied were associated with a higher rate of ETV/CPC failure: Grade IV hemorrhage, weight 3 kg or less and age younger than 3 months at the time of surgery, need for reservoir placement, and presence of a normal cerebral aqueduct. Two factors were found to be statistically significant: the patient’s corrected gestational age of less than 0 weeks at surgery and a narrow prepontine cistern on MRI. The majority (83%) of ETV/CPC failures occurred in the first 3 months after the procedure. None of the patients had a complication directly related to the procedure.

Endoscopic third ventriculostomy/CPC is a safe initial procedure for hydrocephalus in premature infants with IVH and hydrocephalus, obviating the need for a shunt in selected patients. Even though the success rate is low (37%), the lower rate of complications in comparison with shunt treatment may justify this procedure in the initial management of hydrocephalus. As several of the studied factors have shown influence on the outcome, patient selection based on these observations might increase the success rate 6).

2005

A total of 710 children underwent ventriculoscopy as candidates for ETV as the primary treatment for hydrocephalus. The ETV was accomplished in 550 children: 266 underwent a combined ETV-CPC procedure and 284 underwent ETV alone. The mean and median ages were 14 and 5 months, respectively, and 443 patients (81%) were younger than 1 year of age. The hydrocephalus was postinfectious (PIH) in 320 patients (58%), nonpostinfectious (NPIH) in 152 (28%), posthemorrhagic in five (1%), and associated with myelomeningocele in 73 (13%). The mean follow up was 19 months for ETV and 9.2 months for ETV-CPC. Overall, the success rate of ETV-CPC (66%) was superior to that of ETV alone (47%) among infants younger than 1 year of age (p < 0.0001). The ETV-CPC combined procedure was superior in patients with a myelomeningocele (76% compared with 35% success, p = 0.0045) and those with NPIH (70% compared with 38% success, p = 0.0025). Although the difference was not significant for PIH (62% compared with 52% success, p = 0.1607), a benefit was not ruled out (power = 0.3). For patients at least 1 year of age, there was no difference between the two procedures (80% success for each, p = 1.0000). The overall surgical mortality rate was 1.3%, and the infection rate was less than 1%.

The ETV-CPC was more successful than ETV alone in infants younger than 1 year of age. In developing countries in which a dependence on shunts is dangerous, ETV-CPC may be the best option for treating hydrocephalus in infants, particularly for those with NPIH and myelomeningocele 7).


1)

Omar AT, Espiritu AI, Spears J. Endoscopic third ventriculostomy with or without choroid plexus coagulation for myelomeningocele-associated hydrocephalus: systematic review and meta-analysis. J Neurosurg Pediatr. 2022 Jan 21:1-9. doi: 10.3171/2021.11.PEDS21505. Epub ahead of print. PMID: 35061994.
2)

Coulter IC, Dewan MC, Tailor J, Ibrahim GM, Kulkarni AV. Endoscopic third ventriculostomy and choroid plexus cauterization (ETV/CPC) for hydrocephalus of infancy: a technical review. Childs Nerv Syst. 2021 May 15. doi: 10.1007/s00381-021-05209-5. Epub ahead of print. PMID: 33991213.
3)

Dewan MC, Naftel RP. The Global Rise of Endoscopic Third Ventriculostomy with Choroid Plexus Cauterization in Pediatric Hydrocephalus. Pediatr Neurosurg. 2016 Dec 22. doi: 10.1159/000452809. [Epub ahead of print] PubMed PMID: 28002814.
4)

Weil AG, Westwick H, Wang S, Alotaibi NM, Elkaim L, Ibrahim GM, Wang AC, Ariani RT, Crevier L, Myers B, Fallah A. Efficacy and safety of endoscopic third ventriculostomy and choroid plexus cauterization for infantile hydrocephalus: a systematic review and meta-analysis. Childs Nerv Syst. 2016 Nov;32(11):2119-2131. PubMed PMID: 27613635.
5)

Dewan MC, Lim J, Morgan CD, Gannon SR, Shannon CN, Wellons JC 3rd, Naftel RP. Endoscopic third ventriculostomy with choroid plexus cauterization outcome: distinguishing success from failure. J Neurosurg Pediatr. 2016 Dec;25(6):655-662. PubMed PMID: 27564786.
6)

Chamiraju P, Bhatia S, Sandberg DI, Ragheb J. Endoscopic third ventriculostomy and choroid plexus cauterization in posthemorrhagic hydrocephalus of prematurity. J Neurosurg Pediatr. 2014 Apr;13(4):433-9. doi: 10.3171/2013.12.PEDS13219. PubMed PMID: 24527862.
7)

Warf BC. Comparison of endoscopic third ventriculostomy alone and combined with choroid plexus cauterization in infants younger than 1 year of age: a prospective study in 550 African children. J Neurosurg. 2005 Dec;103(6 Suppl):475-81. PubMed PMID: 16383244.

Plasma p-tau181

Plasma p-tau181

Frank et al. from the Boston University School of Medicine examined the ability of plasma hyperphosphorylated tau (p-tau)181 to detect cognitive impairment due to Alzheimer’s disease (AD) independently and in combination with plasma total tau (t-tau) and neurofilament light (NfL).

Plasma samples were analyzed using the Simoa platform for 235 participants with normal cognition (NC), 181 with mild cognitive impairment due to AD (MCI), and 153 with AD dementia. Statistical approaches included multinomial regression and Gaussian graphical models (GGMs) to assess a network of plasma biomarkers, neuropsychological tests, and demographic variables.

Plasma p-tau181 discriminated AD dementia from NC, but not MCI, and correlated with dementia severity and worse neuropsychological test performance. Plasma NfL similarly discriminated diagnostic groups. Unlike plasma NfL or t-tau, p-tau181 had a direct association with cognitive diagnosis in a bootstrapped GGM.

These results support plasma p-tau181 for the detection of Alzheimer’s disease dementia and the use of blood-based biomarkers for optimal disease detection 1).


Results suggest that in elderly individuals without dementia at baseline, plasma p-tau181 biomarkers were associated with greater memory decline and rates of clinical progression to dementia. Plasma p-tau181 improved prediction of memory decline above a model with currently available clinical and genetic data. While the clinical importance of this improvement in the prediction of memory decline is unknown, these results highlight the potential of plasma p-tau181 as a cost-effective and scalable Alzheimer’s disease biomarker 2)


Plasma p-tau231 is a promising novel biomarker of emerging AD pathology with the potential to facilitate clinical trials to identify vulnerable populations below the PET threshold of amyloid-β positivity or apparent entorhinal tau deposition. 3).


The study of Karikari et al. adds significant weight to the growing body of evidence in the use of plasma p-tau181 as a non-invasive diagnostic and prognostic tool for AD, regardless of clinical stage, which would be of great benefit in clinical practice and a large cost-saving in clinical trial recruitment. 4)


O’Connor et al. investigated the timing of p-tau181 changes using 153 blood samples from 70 individuals in a longitudinal study of familial AD (FAD). Plasma p-tau181 was measured, using an in-house single-molecule array assay. We compared p-tau181 between symptomatic carriers, presymptomatic carriers, and non-carriers, adjusting for age and sex. We examined the relationship between p-tau181 and neurofilament light and estimated years to/from symptom onset (EYO), as well as years to/from the actual onset in asymptomatic subgroup. In addition, we studied associations between p-tau181 and clinical severity, as well as testing for differences between genetic subgroups. Twenty-four were presymptomatic carriers (mean baseline EYO -9.6 years) while 27 were non-carriers. Compared with non-carriers, plasma p-tau181 concentration was higher in both symptomatic (p < 0.001) and presymptomatic mutation carriers (p < 0.001). Plasma p-tau181 showed considerable intra-individual variability but individual values discriminated symptomatic (AUC 0.93 [95% CI 0.85-0.98]) and presymptomatic (EYO ≥ -7 years) (AUC 0.86 [95% CI 0.72-0.94]) carriers from non-carriers of the same age and sex. From a fitted model, there was evidence (p = 0.050) that p-tau181 concentrations were higher in mutation carriers than non-carriers from 16 years prior to estimated symptom onset. Our finding that plasma p-tau181 concentration is increased in symptomatic and presymptomatic FAD suggests potential utility as an easily accessible biomarker of AD pathology. 5).


1)

Frank B, Ally M, Brekke B, Zetterberg H, Blennow K, Sugarman MA, Ashton NJ, Karikari TK, Tripodis Y, Martin B, Palmisano JN, Steinberg EG, Simkina I, Turk KW, Budson AE, O’Connor MK, Au R, Goldstein LE, Jun GR, Kowall NW, Stein TD, McKee AC, Killiany R, Qiu WQ, Stern RA, Mez J, Alosco ML. Plasma p-tau181 shows stronger network association to Alzheimer’s disease dementia than neurofilament light and total tau. Alzheimers Dement. 2021 Dec 2. doi: 10.1002/alz.12508. Epub ahead of print. PMID: 34854549.
2)

Therriault J, Benedet AL, Pascoal TA, Lussier FZ, Tissot C, Karikari TK, Ashton NJ, Chamoun M, Bezgin G, Mathotaarachchi S, Gauthier S, Saha-Chaudhuri P, Zetterberg H, Blennow K, Rosa-Neto P; Alzheimer’s Disease Neuroimaging Initiative. Association of plasma P-tau181 with memory decline in non-demented adults. Brain Commun. 2021 Jun 14;3(3):fcab136. doi: 10.1093/braincomms/fcab136. PMID: 34222875; PMCID: PMC8249102.
3)

Ashton NJ, Pascoal TA, Karikari TK, Benedet AL, Lantero-Rodriguez J, Brinkmalm G, Snellman A, Schöll M, Troakes C, Hye A, Gauthier S, Vanmechelen E, Zetterberg H, Rosa-Neto P, Blennow K. Plasma p-tau231: a new biomarker for incipient Alzheimer’s disease pathology. Acta Neuropathol. 2021 May;141(5):709-724. doi: 10.1007/s00401-021-02275-6. Epub 2021 Feb 14. PMID: 33585983; PMCID: PMC8043944.
4)

Karikari TK, Benedet AL, Ashton NJ, Lantero Rodriguez J, Snellman A, Suárez- Calvet M, Saha-Chaudhuri P, Lussier F, Kvartsberg H, Rial AM, Pascoal TA, Andreasson U, Schöll M, Weiner MW, Rosa-Neto P, Trojanowski JQ, Shaw LM, Blennow K, Zetterberg H; Alzheimer’s Disease Neuroimaging Initiative. Diagnostic performance and prediction of clinical progression of plasma phospho-tau181 in the Alzheimer’s Disease Neuroimaging Initiative. Mol Psychiatry. 2021 Feb;26(2):429-442. doi: 10.1038/s41380-020-00923-z. Epub 2020 Oct 26. PMID: 33106600.
5)

O’Connor A, Karikari TK, Poole T, Ashton NJ, Lantero Rodriguez J, Khatun A, Swift I, Heslegrave AJ, Abel E, Chung E, Weston PSJ, Pavisic IM, Ryan NS, Barker S, Rossor MN, Polke JM, Frost C, Mead S, Blennow K, Zetterberg H, Fox NC. Plasma phospho-tau181 in presymptomatic and symptomatic familial Alzheimer’s disease: a longitudinal cohort study. Mol Psychiatry. 2020 Jul 14. doi: 10.1038/s41380-020-0838-x. Epub ahead of print. PMID: 32665603.

Idiopathic normal pressure hydrocephalus

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