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Post-haemorrhagic hydrocephalus is associated with poorer surgical and neurodevelopmental sequelae than other causes of infant hydrocephalus.

ABSTRACT:

Purpose

This retrospective cohort study aimed to investigate the surgical and neurodevelopmental outcomes (NDO) of infant hydrocephalus. We also sought to determine whether these outcomes are disproportionately poorer in post-haemorrhagic hydrocephalus (PHH) compared to other causes of infant hydrocephalus.

Methods

A review of all infants with hydrocephalus who had ventriculoperitoneal (VP) shunts inserted at Great Ormond Street Hospital (GOSH) from 2008 to 2018 was performed. Demographic, surgical, neurodevelopmental, and other clinical data extracted from electronic patient notes were analysed by aetiology. Shunt survival, NDO, cerebral palsy (CP), epilepsy, speech delay, education, behavioural disorders, endocrine dysfunction, and mortality were evaluated.

Results

A total of 323 infants with median gestational age of 37.0 (23.29-42.14) weeks and birthweight of 2640 g (525-4684 g) were evaluated. PHH was the most common aetiology (31.9%) and was associated with significantly higher 5-year shunt revision rates, revisions beyond a year, and median number of revisions than congenital or "other" hydrocephalus (all p < 0.02). Cox regression demonstrated poorest shunt survival in PHH, related to gestational age at birth and corrected age at shunt insertion. PHH also had the highest rate of severe disabilities, increasing with age to 65.0% at 10 years, as well as the highest CP rate; only genetic hydrocephalus had significantly higher endocrine dysfunction (p = 0.01) and mortality rates (p = 0.04).

Conclusions

Infants with PHH have poorer surgical and NDO compared to all other aetiologies, except genetic hydrocephalus. Research into measures of reducing neurodisability following PHH is urgently required. Long-term follow-up is essential to optimise support and outcomes.

SUBMITTER: Mohamed M

PROVIDER: S-EPMC8578110 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundIntraventricular hemorrhage (IVH) and post-hemorrhagic hydrocephalus (PHH) have a complex pathophysiology involving inflammatory response, ventricular zone and cell-cell junction disruption, and choroid-plexus (ChP) hypersecretion. Increased cerebrospinal fluid (CSF) cytokines, extracellular matrix proteins, and blood metabolites have been noted in IVH/PHH, but osmolality and electrolyte disturbances have not been evaluated in human infants with these conditions. We hypothesized that CSF total protein, osmolality, electrolytes, and immune cells increase in PHH.MethodsCSF samples were obtained from lumbar punctures of control infants and infants with IVH prior to the development of PHH and any neurosurgical intervention. Osmolality, total protein, and electrolytes were measured in 52 infants (18 controls, 10 low grade (LG) IVH, 13 high grade (HG) IVH, and 11 PHH). Serum electrolyte concentrations, and CSF and serum cell counts within 1-day of clinical sampling were obtained from clinical charts. Frontal occipital horn ratio (FOR) was measured for estimating the degree of ventriculomegaly. Dunn or Tukey's post-test ANOVA analysis were used for pair-wise comparisons.ResultsCSF osmolality, sodium, potassium, and chloride were elevated in PHH compared to control (p = 0.012 - < 0.0001), LGIVH (p = 0.023 - < 0.0001), and HGIVH (p = 0.015 - 0.0003), while magnesium and calcium levels were higher compared to control (p = 0.031) and LGIVH (p = 0.041). CSF total protein was higher in both HGIVH and PHH compared to control (p = 0.0009 and 0.0006 respectively) and LGIVH (p = 0.034 and 0.028 respectively). These differences were not reflected in serum electrolyte concentrations nor calculated osmolality across the groups. However, quantitatively, CSF sodium and chloride contributed 86% of CSF osmolality change between control and PHH; and CSF osmolality positively correlated with CSF sodium (r, p = 0.55,0.0015), potassium (r, p = 0.51,0.0041), chloride (r, p = 0.60,0.0004), but not total protein across the entire patient cohort. CSF total cells (p = 0.012), total nucleated cells (p = 0.0005), and percent monocyte (p = 0.016) were elevated in PHH compared to control. Serum white blood cell count increased in PHH compared to control (p = 0.042) but there were no differences in serum cell differential across groups. CSF total nucleated cells also positively correlated with CSF osmolality, sodium, potassium, and total protein (p = 0.025 - 0.0008) in the whole cohort.ConclusionsCSF osmolality increased in PHH, largely driven by electrolyte changes rather than protein levels. However, serum electrolytes levels were unchanged across groups. CSF osmolality and electrolyte changes were correlated with CSF total nucleated cells which were also increased in PHH, further suggesting PHH is a neuro-inflammatory condition.

Project description:BACKGROUND:Postinfectious hydrocephalus in infants is a major health problem in sub-Saharan Africa. The conventional treatment is ventriculoperitoneal shunting, but surgeons are usually not immediately available to revise shunts when they fail. Endoscopic third ventriculostomy with choroid plexus cauterization (ETV-CPC) is an alternative treatment that is less subject to late failure but is also less likely than shunting to result in a reduction in ventricular size that might facilitate better brain growth and cognitive outcomes. METHODS:We conducted a randomized trial to evaluate cognitive outcomes after ETV-CPC versus ventriculoperitoneal shunting in Ugandan infants with postinfectious hydrocephalus. The primary outcome was the Bayley Scales of Infant Development, Third Edition (BSID-3), cognitive scaled score 12 months after surgery (scores range from 1 to 19, with higher scores indicating better performance). The secondary outcomes were BSID-3 motor and language scores, treatment failure (defined as treatment-related death or the need for repeat surgery), and brain volume measured on computed tomography. RESULTS:A total of 100 infants were enrolled; 51 were randomly assigned to undergo ETV-CPC, and 49 were assigned to undergo ventriculoperitoneal shunting. The median BSID-3 cognitive scores at 12 months did not differ significantly between the treatment groups (a score of 4 for ETV-CPC and 2 for ventriculoperitoneal shunting; Hodges-Lehmann estimated difference, 0; 95% confidence interval [CI], -2 to 0; P=0.35). There was no significant difference between the ETV-CPC group and the ventriculoperitoneal-shunt group in BSID-3 motor or language scores, rates of treatment failure (35% and 24%, respectively; hazard ratio, 0.7; 95% CI, 0.3 to 1.5; P=0.24), or brain volume (z score, -2.4 and -2.1, respectively; estimated difference, 0.3; 95% CI, -0.3 to 1.0; P=0.12). CONCLUSIONS:This single-center study involving Ugandan infants with postinfectious hydrocephalus showed no significant difference between endoscopic ETV-CPC and ventriculoperitoneal shunting with regard to cognitive outcomes at 12 months. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01936272 .).