Establishing connectivity through microdissections of midbrain stimulation-related neural circuits.

Comprehensive understanding of the neural circuits involving the ventral tegmental area is essential for elucidating the anatomo-functional mechanisms governing human behaviour as well as the therapeutic and adverse effects of deep brain stimulation for neuropsychiatric diseases. While the ventral tegmental area has been successfully targeted with deep brain stimulation for different neuropsychiatric diseases, the axonal connectivity of the region has not been fully understood. Here using fiber micro-dissections in human cadaveric hemispheres, population-based high-definition fiber tractography, and previously reported deep brain stimulation hotspots, we find that the ventral tegmental area participates in an intricate network involving the serotonergic pontine nuclei, basal ganglia, limbic system, basal forebrain, and prefrontal cortex, which is implicated in the treatment of obsessive-compulsive disorder, major depressive disorder, Alzheimer's disease, cluster headaches, and aggressive behaviors.

Unveiling the axonal connectivity between the precuneus and temporal pole: Structural evidence from the cingulum pathways.

Neuroimaging studies have consistently demonstrated concurrent activation of the human precuneus and temporal pole (TP), both during resting-state conditions and various higher-order cognitive functions. However, the precise underlying structural connectivity between these brain regions remains uncertain despite significant advancements in neuroscience research. In this study, we investigated the connectivity of the precuneus and TP by employing parcellation-based fiber micro-dissections in human brains and fiber tractography techniques in a sample of 1065 human subjects and a sample of 41 rhesus macaques. Our results demonstrate the connectivity between the posterior precuneus area POS2 and the areas 35, 36, and TG of the TP via the fifth subcomponent of the cingulum (CB-V) also known as parahippocampal cingulum. This finding contributes to our understanding of the connections within the posteromedial cortices, facilitating a more comprehensive integration of anatomy and function in both normal and pathological brain processes. PRACTITIONER POINTS: Our investigation delves into the intricate architecture and connectivity patterns of subregions within the precuneus and temporal pole, filling a crucial gap in our knowledge. We revealed a direct axonal connection between the posterior precuneus (POS2) and specific areas (35, 35, and TG) of the temporal pole. The direct connections are part of the CB-V pathway and exhibit a significant association with the cingulum, SRF, forceps major, and ILF. Population-based human tractography and rhesus macaque fiber tractography showed consistent results that support micro-dissection outcomes.

The lateral retrocanthal transorbital endoscopic approach to the middle fossa: cadaveric stepwise approach and review of quantitative cadaveric data.

OBJECTIVE: The lateral retrocanthal transorbital endoscopic approach (LRCTEA) facilitates trajectory to the middle fossa, preserving the lateral canthal tendon and thus avoiding postoperative complications such as eyelid malposition. Here, the authors sought to define the surgical anatomy and technique of LRCTEA using a stepwise approach in cadaveric heads and offer an in-depth examination of existing quantitative data from cadaveric studies. METHODS: The authors performed LRCTEA to the middle cranial fossa under neuronavigation in 7 cadaveric head specimens that underwent high-resolution (1-mm) CT scans preceding the dissections. RESULTS: The LRCTEA provided access to middle fossa regions including the cavernous sinus, Meckel's cave, and medial temporal lobe. The trajectories and endpoints of the approach were confirmed using electromagnetic neuronavigation. A stepwise approach was delineated and recorded. CONCLUSIONS: The authors' cadaveric study delineates the surgical anatomy and technique of the LRCTEA, providing a stepwise approach for its implementation. As these approaches continue to evolve, their development and refinement will play an important role in expanding the surgical options available to neurosurgeons, ultimately improving outcomes for patients with complex skull base pathologies. The LRCTEA presents a promising advancement in skull base surgery, particularly for accessing challenging middle fossa regions. However, surgeons must remain vigilant to potential complications, including transient diplopia, orbital hematoma, or damage to the optic apparatus.

Anatomical and surgical characteristics correlate with pachymeningeal failure in patients with brain metastases after neurosurgical resection and adjuvant stereotactic radiosurgery.

PURPOSE: Neurosurgery (NS) is an essential modality for large brain metastases (BM). Postoperative stereotactic radiosurgery (SRS) is the standard of care adjuvant treatment. Pachymeningeal failure (PMF) is a newly described entity, distinct from classical leptomeningeal failure (LMF), that is uniquely observed in postoperative patients treated with adjuvant SRS. We sought to identify risk factors for PMF in patients treated with NS + SRS. METHODS: From a prospective registry (2009 to 2021), we identified all patients treated with NS + SRS. Clinical, imaging, pathological, and treatment factors were analyzed. PMF incidence was evaluated using a competing risks model. RESULTS: 144 Patients were identified. The median age was 62 (23-90). PMF occurred in 21.5% (31/144). Female gender [Hazard Ratio (HR) 2.65, p = 0.013], higher Graded Prognostic Assessment (GPA) index (HR 2.4, p < 0.001), absence of prior radiation therapy (HR N/A, p = 0.018), controlled extracranial disease (CED) (HR 3.46, p = 0.0038), and pia/dura contact (PDC) (HR 3.30, p = 0.0053) were associated with increased risk for PMF on univariate analysis. In patients with PDC, wider target volumes correlated with reduced risk of PMF. Multivariate analysis indicated PDC (HR 3.51, p = 0.0053), piecemeal resection (HR 2.38, p = 0.027), and CED (HR 3.97, p = 0.0016) independently correlated with PMF risk. PMF correlated with reduced OS (HR 2.90, p < 0.001) at a lower rate compared to LMF (HR 10.15, p < 0.001). CONCLUSION: PMF correlates with tumor PDC and piecemeal resection in patients treated with NS + SRS. For unclear reasons, it is also associated with CED. In tumors with PDC, wider dural radiotherapy coverage was associated with a lower risk of PMF.

Pachymeningeal disease: a systematic review and metanalysis.

BACKGROUND: Pachymeningeal disease (PMD) is a newly recognized pattern of brain metastasis (BrM) failure that specifically occurs following surgery with adjuvant stereotactic radiosurgery (SRS) and has unique prognostic implications relative to leptomeningeal disease (LMD). Here, we report its prevalence, prognostic implications, and associated risk factors. METHODS: A literature search was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses on PUBMED and Cochrane from January 2000 to June 2023. RESULTS: We identified 12 studies that included a total of 3992 BrM patients, 659 (16.5%) of whom developed meningeal disease (MD) following surgery plus adjuvant SRS, including either PMD or LMD. The mean prevalence of MD across studies was 20.9% (7.9-38.0%), with PMD accounting for 54.6% of this prevalence and LMD comprising the remaining 45.4%. Mean of the median overall survivals following diagnosis of PMD and LMD was 10.6 months and 3.7 months p = 0.007, respectively, a significant difference. Only 2 risk factors for PMD were reported in ≥ 2 studies and also identified as statistically significant per our meta-analysis: infratentorial location and controlled systemic disease status. CONCLUSION: While PMD has a superior prognosis to LMD, it is nevertheless a critical oncologic event associated with significant mortality and remains poorly recognized. PMD is predominantly observed in patients with controlled systemic disease status and infratentorial location. Future treatment strategies should focus on reducing surgical seeding and sterilizing surgical cavities.

Endoscopic endonasal surgery for prolactinomas: prognostic factors for disease control and management of persistent disease.

Only a limited number of studies have focused on the results of the Endoscopic Endonasal Approach (EEA) for treatment of prolactinomas. We sought to assess the effectiveness of EEA for prolactinoma surgery, identify factors for disease remission, and present our approach for the management of persistent disease. Forty-seven prolactinomas operated over 10 years, with a mean follow-up of 59.9 months, were included. The primary endpoints were early disease remission and remission at last follow-up. Resistance/intolerance to DA were surgical indications in 76.7%. Disease remission was achieved in 80% of microprolactinomas and 100% of microprolactinomas enclosed by the pituitary. Early disease remission was correlated with female gender (p=0.03), lower preoperative PRL levels (p=0.014), microadenoma (p=0.001), lack of radiological hemorrhage (p=0.001), absence of cavernous sinus (CS) invasion (p<0.001), and extent of resection (EOR) (p<0.001). Persistent disease was reported in 48.9% of patients, with 47% of them achieving remission at last follow-up with DA therapy alone. Repeat EEA and/or radiotherapy were utilized in 6 patients, with 66.7% achieving remission. Last follow-up remission was achieved in 76.6%, with symptomatic improvement in 95.8%. Factors predicting last follow-up remission were no previous operation (p=0.001), absence of CS invasion (p=0.01), and EOR (p<0.001). Surgery is effective for disease control in microprolactinomas. In giant and invasive tumors, it may significantly reduce the tumor volume. A multidisciplinary approach may lead to long-term disease control in three-quarters of patients, with symptomatic improvement in an even greater proportion.

Postoperative CT scans after resection of brain metastases: neurosurgical routine or added value?

BACKGROUND: Metastasis is the most common brain tumor in adults. It is the standard of care at most North American centers to obtain an early postoperative imaging after their resection. However, the necessity of this practice in the absence of a new postoperative deficit remains unclear. METHODS: We retrospectively reviewed our surgical cohort of patients who underwent resection of brain metastases from July 2018 to June 2019. We collected demographic data and reviewed results of routine postoperative CT scans and neurological morbidities to examine the diagnostic and therapeutic yield of an early postoperative scan. In addition, we performed a systematic review of the topic. RESULTS: Our review included 130 patients, all of whom underwent gross total resection of one or more brain metastases. On postoperative CT, none had unexpected findings such as cavity hematoma or new ischemia; no changes in management resulted from postoperative imaging. One patient required a higher dose of dexamethasone on postoperative day 4 for delayed hemiparesis and aphasia due to cerebral edema. Three additional patients underwent a wound washout for delayed infection during a subsequent admission. Our systematic review identified three additional studies; in a combined cohort of 450 patients (including our own), no patients had clinically actionable findings on routine postoperative CT. CONCLUSIONS: Following resection of brain metastases, a routine postoperative CT scan has low diagnostic yield and did not change patient management in any cases examined in this work.

Defining the limits and indications of the Draf III endoscopic approach to the lateral frontal sinus and maximizing visualization and maneuverability: a cadaveric and radiological study.

PURPOSE: The DRAF III procedure has been used for access to the lateralmost part of the frontal sinus. We sought to identify anatomical and radiological measurements as well as modifications that predict the lateral limits of visualization and surgical access after this procedure. METHODS: Seven cadaver heads were imaged with computed tomography scan. The distance from midline to the medial orbital wall (MOWD), midline to the lateral end of the frontal sinus (MLD), the sum of MLDs (SMLD), interorbital distance (IOD) and the shortest anteroposterior distance of the frontal recess (APD) were utilized. The ratios MLD/MOWD, and SMLD/IOD were calculated. The same distances were measured on 41 CT scans. Orbital transposition (OT) and partial resection of the piriform aperture (PAR) were performed; the visualization and reach were assessed. The angle of insertion was measured before and after the modifications. RESULTS: Only the ratio MLD/MOWD was consistently predictive of access to the lateral, superior and posterior wall of the frontal sinus. Following the modifications, a visualization of 100% laterally was achieved with the 30- and 45 degree endoscopes and every lateral recess could be reached with the 70 degree suction. A mean increase of the angle of insertion of 25.3 and 59.6% was recorded after OT and PAR, respectively. CONCLUSIONS: IOD rather than APD defines the limits of the Draf III approach to the lateral frontal sinus and MLD/MOWD ratio can serve as a useful preoperative tool. Along to the already described OT, PAR increases visualization and reach of the lateral frontal sinus.

A stepwise laboratory manual for the dissection and illustration of limbic and paralimbic structures: lessons learned from the Klingler's technique.

BACKGROUND: Three-dimensional relationships within the limbic and paralimbic areas are often hard to grasp. Relevant anatomical structures exhibit a complicated architecture and connectivity and therefore surgical approaches targeting lesions or functional resections in this area pose a distinct challenge. PURPOSE: To provide an educational, comprehensive, systematic and stepwise manual for the dissection and illustration of major limbic structures since there is a gap in the pertinent literature. Further, we aim to offer a thorough yet simplified roadmap for laboratory and intraoperative dissections. METHODS: Twenty (20) normal adult, formalin-fixed cerebral hemispheres were studied through the fiber dissection technique and under the microscope. Stepwise and in tandem medial to lateral and lateral to medial dissections were performed in all specimens aiming to reveal the morphology and spatial relationships of major limbic and paralimbic areas. RESULTS: Fourteen (14) consecutive, discrete and easily reproducible laboratory anatomical steps are systematically described to reveal the intricate anatomy of the limbic and paralimbic structures and their main connections. CONCLUSION: This study offers for the first time in the pertinent literature a focused, step-by-step laboratory manual for the dissection and illustration of the limbic and paralimbic structures. The overreaching goal is to supplement the novice and experienced anatomist and neurosurgeon with a thorough and systematic reference to facilitate laboratory or intraoperative dissections.

Dissociation between visuospatial neglect assessment tasks and its neuroanatomical substrates: a case report.

Visuospatial neglect possesses significant heterogeneity in clinical features and neuroanatomical substrates. Behavioral dissociations on different neglect tasks have been reported in the past, and the investigation of their respective anatomical correlates at cortical and, to a lesser degree, subcortical levels has been attempted in stroke studies. We report a patient with a neoplasm occupying the right ventral post-central gyrus and anterior supramarginal gyrus. The patient was admitted preoperatively with dissociation on the performance of neglect tasks, showing clinical deficits in the line bisection task and clock drawing, but not on the cancelation task. The patient underwent an awake craniotomy for tumor excision. Intraoperative visuospatial mapping was employed by applying direct electrical stimulation (DES) to the supramarginal gyrus and the ventral branch of the superior longitudinal fasciculus (SLF III) during the line bisection task. According to our findings, DES was ineffective at the cortical level, but it induced strong rightward bias when applied subcortically at the SLF III. By combining our preoperative and intraoperative anatomical and clinical data, we suggest that the posterior part of the SLF III might have a distinct role in the perceptual component of neglect. Our findings are discussed within the context of previous literature supporting the notion that particular behavioral features of spatial neglect are mediated by different white-matter connections.

Mapping the superficial morphology of the occipital lobe: proposal of a universal nomenclature for clinical and anatomical use.

The superficial anatomy of the occipital lobe has been described as irregular and highly complex. This notion mainly arises from the variability of the regional sulco-gyral architecture. Our aim was to investigate the prevalence, morphology, and correlative anatomy of the sulci and gyri of the occipital region in cadaveric specimens and to summarize the nomenclature used in the literature to describe these structures. To this end, 33 normal, adult, formalin-fixed hemispheres were studied. In addition, a review of the relevant literature was conducted with the aim to compare our findings with data from previous studies. Hence, in the lateral occipital surface, we recorded the lateral occipital sulcus and the intraoccipital sulcus in 100%, the anterior occipital sulcus in 24%, and the inferior occipital sulcus in 15% of cases. In the area of the occipital pole, we found the transverse occipital sulcus in 88% of cases, the lunate sulcus in 64%, the occipitopolar sulcus in 24%, and the retrocalcarine sulcus in 12% of specimens. In the medial occipital surface, the calcarine fissure and parieto-occipital sulcus were always present. Finally, the basal occipital surface was always indented by the posterior occipitotemporal and posterior collateral sulci. A sulcus not previously described in the literature was identified on the supero-lateral aspect of the occipital surface in 85% of cases. We named this sulcus "marginal occipital sulcus" after its specific topography. In this study, we offer a clear description of the occipital surface anatomy and further propose a standardized taxonomy for clinical and anatomical use.

A systematic review of surgical treatments of idiopathic intracranial hypertension (IIH).

Idiopathic intracranial hypertension denotes raised intracranial pressure in the absence of an identifiable cause and presents with symptoms relating to elevated ICP, namely headaches and visual deterioration. Treatment of IIH aims at reducing intracranial pressure, relieving headache and salvaging patients' vision. Surgical interventions are recommended for medically refractory IIH and include CSF diversion techniques, optic nerve sheath fenestration, bariatric surgery and venous sinus stenting. Prospective studies on the surgical options for IIH are scant and no evidence-based guidelines for the surgical management of medically refractory IIH have been established. A search in Cochrane Library, MEDLINE and EMBASE from 1 January 1985 to 19 April 2019 for controlled or observational studies on the surgical treatment of IIH (defined in accordance with the modified Dandy or the modified Friedman criteria) in adults yielded 109 admissible studies. VSS improved papilledema, visual fields and headaches in 87.1%, 72.7% and 72.1% of the patients respectively, with a 2.3% severe complication rate and 11.3% failure rate. CSF diversion techniques diminished papilledema, visual field deterioration and headaches in 78.9%, 66.8% and 69.8% of the cases and are associated with a 9.4 severe complication rate and a 43.4% failure rate. ONSF ameliorated papilledema, visual field defects and headaches in 90.5, 65.2% and 49.3% of patients. Severe complication rate was 2.2% and failure rate was 9.4%. This is currently the largest systematic review for the available operative modalities for IIH. VSS provided the best results in headache resolution and visual outcomes, with low failure rates and a very favourable complication profile. In light of this, VSS ought to be regarded as the first-line surgical modality for the treatment of medically refractory IIH.

The corticotegmental connectivity as an integral component of the descending extrapyramidal pathway: novel and direct structural evidence stemming from focused fiber dissections.

This study opts to investigate the thus far ill-defined intra-hemispheric topography, morphology, and connectivity of the extrapyramidal fibers that originate from the frontoparietal cortex and project to the tegmental area and to explore structural correlations to the pyramidal pathway. To this end, twenty normal adult, formalin-fixed cerebral hemispheres were studied through the fiber micro-dissection technique. Stepwise and in-tandem medial to lateral and lateral to medial dissections were carried out in all specimens. The cortical termination of the fibers under investigation was carefully defined, and their entry zone at the tegmental area was meticulously recorded. We consistently identified the corticotegmental tract (CTT) as a distinct fiber pathway lying in the white matter of the genu and posterior limb of the internal capsule and travelling medial to the corticospinal tract (CST) and lateral to the thalamic radiations. The CTT exhibits a fan-shaped configuration and can be classified into three discrete segments: a rostral one receiving fibers from BA8 (pre-SMA, frontal eye fields, dorsal prefrontal cortex), a middle one arising from areas BA4 and BA6 (primary motor cortex and premotor cortex), and a caudal one stemming from areas BA1/2/3 (somatosensory cortex). The anatomical location, configuration, trajectory, and axonal connectivity of this tract are attuned to the descending component of the extrapyramidal system, and therefore, it is believed to be implicated in locomotion, postural control, motor inhibition, and motor modification. Our results provide further support on the emerging concept of a dynamic, parallel, and delocalized theory for complex human motor behavior.

Endoscopic extra-capsular resection of a giant pituitary adenoma: how I do it.

BACKGROUND: Giant pituitary adenomas are characterized by their large size and potential to invade parasellar and suprasellar regions leading to visual decline and hypopituitarism. Thus, they remain a significant surgical challenge, and gross total removal is only achieved in the minority of cases. METHOD: We aim to describe the key surgical steps for endoscopic extra-capsular resection of a giant pituitary adenoma with the aim of achieving complete tumor resection with description of the relevant surgical anatomy, indications and limitations. CONCLUSION: Endoscopic extra-capsular resection of giant pituitary tumors when feasible allows for complete tumor resection, early identification of the gland and avoidance of manipulation of the optic apparatus.

Angiosarcoma-related cerebral metastases: a systematic review of the literature.

Angiosarcoma-related cerebral metastases have only been recorded in a few case reports and case series and have not been systematically reviewed to date. Our objective was therefore to perform a systematic literature review on cases of angiosarcomas metastasizing to the brain to inform current practice. All three major libraries-PubMed/MEDLINE, Embase, and Cochrane-were systematically searched, until January 2019. Articles in English reporting angiosarcoma-related cerebral metastases via hematogenous route were included. Our search yielded 45 articles (38 case reports, 5 retrospective studies, 1 case series and 1 letter to the editor), totaling 48 patients (mean age 47.9 years). The main primary site was the heart. The mean time of diagnosis of cerebral metastases following primary tumor identification was 4.9 months. In 15 cases, the brain was the only metastatic site. In cases of multiple extracerebral metastases, the most common sites were the lung and bone. Acute intracerebral supratentorial hemorrhage was the most common presenting radiological feature. Treatment strategies were almost equally divided between the surgical (with or without adjuvant treatment) and the medical arm. Mean overall survival was 7.2 months while progression-free survival was 1.5 months. To our knowledge, this is the first systematic literature review on angiosarcoma-related cerebral metastases. This pathology proves to be an extremely rare clinical entity and carries a poor prognosis, and no consensus has been reached regarding treatment.

Intrathecal Baclofen Therapy for Painful Muscle Spasms in a Patient with Friedreich's Ataxia.

Friedreich's ataxia (FA) is the most frequent hereditary ataxia syndrome, while painful muscle spasms and spasticity have been reported in 11-15% of FA patients. This report describes the successful management of painful spasms in a 65-year-old woman with FA via intrathecal baclofen (ITB) therapy following unsuccessful medical treatments. To our knowledge, this is the third reported case in the literature. Unfortunately, the pathophysiological characteristics of muscle spasms in FA are not well explored and understood while the therapeutic mechanisms of the different treatments are rather vague. Taking into consideration the suggested spinal atrophy in FA, the clinical resemblance of FA and chronic spinal injury muscle spasms, together with the rapid ITB therapy effectiveness in alleviating FA muscle spasms, we attempted to suggest a putative pathophysiological mechanism acting at the spinal level and possibly explained by the presence of independent spinal locomotor systems producing muscle spasms. Specifically, overexcitement of these centers, due to loss of normal regulation from upper CNS levels, may result in the uncontrolled firing of secondary motor neurons and may be the key to producing muscle spasms. However, further research under experimental and clinical settings seems to be necessary.

Efficacy, complications and cost of surgical interventions for idiopathic intracranial hypertension: a systematic review of the literature.

BACKGROUND: To define the efficacy, complication profile and cost of surgical options for treating idiopathic intracranial hypertension (IIH) with respect to the following endpoints: vision and headache improvement, normal CSF pressure restoration, papilloedema resolution, relapse rate, operative complications, cost of intervention and quality of life. METHODS: A systematic review of the surgical treatment of IIH was carried out. Cochrane Library, MEDLINE and EMBASE databases were systematically searched from 1985 to 2014 to identify all relevant manuscripts written in English. Additional studies were identified by searching the references of retrieved papers and relative narrative reviews. RESULTS: Forty-one (41) studies were included (36 case series and 5 case reports), totalling 728 patients. Three hundred forty-one patients were treated with optic nerve sheath fenestration (ONSF), 128 patients with lumboperitoneal shunting (LPS), 72 patients with ventriculoperitoneal shunting (VPS), 155 patients with venous sinus stenting and 32 patients with bariatric surgery. ONSF showed considerable efficacy in vision improvement, while CSF shunting had a superior headache response. Venous sinus stenting demonstrated satisfactory results in both vision and headache improvement along with the best complication profile and low relapse rate, but longer follow-up periods are needed. The complication rate of bariatric surgery was high when compared to other interventions and visual outcomes have not been reported adequately. ONSF had the lowest cost. CONCLUSIONS: No surgical modality proved to be clearly superior to any other in IIH management. However, in certain contexts, a given approach appears more justified. Therefore, a treatment algorithm has been formulated, based on the extracted evidence of this review. The traditional treatment paradigm may need to be re-examined with sinus stenting as a first-line treatment modality.

Finger tapping and verbal fluency post-tap test improvement in INPH: its value in differential diagnosis and shunt-treatment outcomes prognosis.

BACKGROUND: Idiopathic normal pressure hydrocephalus (INPH) diagnosis is challenging as it can be mimicked by other neurological conditions, such as neurodegenerative dementia and motor syndromes. Additionally, outcomes after lumbar puncture (LP) tap test and shunt treatment may vary due to the lack of a common protocol in INPH assessment. The present study aimed to assess whether a post-LP test amelioration of frontal cognitive dysfunctions, characterizing this syndrome, can differentiate INPH from similar neurological conditions and whether this improvement can predict INPH post-shunt outcomes. METHOD: Seventy-one consecutive patients referred for INPH suspicion and LP testing, were enrolled. According to the consensus guidelines criteria, 29 patients were diagnosed as INPH and 42 were assigned an alternative diagnosis (INPH-like group) after reviewing clinical, neuropsychological and imaging data, and before LP results. A comprehensive neuropsychological assessment for frontal executive, upper extremity fine motor functions, aphasias, apraxias, agnosias and gait evaluation were administered at baseline. Executive, fine motor functions and gait were re-examined post-LP test in all patients and post-shunt placement in INPH patients. RESULTS: Of the INPH patients, 86.2% showed cognitive amelioration in the post-LP test; in addition, all but one (97%) presented with neurocognitive and gait improvement post-shunt. Verbal phonological fluency and finger tapping task post-LP improvement predicted positive clinical outcome post-shunt. None of the INPH-like group presented with neurocognitive improvement post-LP. CONCLUSIONS: Post-LP amelioration of verbal fluency and finger tapping deficits can differentiate INPH from similar disorders and predict positive post-shunt clinical outcome in INPH. This becomes of great importance when gait assessment is difficult to perform in clinical practice.

Maternal environmental risk factors for congenital hydrocephalus: a systematic review.

OBJECTIVE Congenital hydrocephalus (CH) is one of the most frequent CNS congenital malformations, representing an entity with serious pathological consequences. Although several studies have previously assessed child-related risk factors associated with CH development, there is a gap of knowledge on maternal environmental risk factors related to CH. The authors have systematically assessed extrinsic factors in the maternal environment that potentially confer an increased risk of CH development. METHODS The Cochrane Library, MEDLINE, and EMBASE were systematically searched for works published between 1966 and December 2015 to identify all relevant articles published in English. Only studies that investigated environmental risk factors concerning the mother-either during gestation or pregestationally-were included. RESULTS In total, 13 studies (5 cohorts, 3 case series, 3 case-control studies, 1 meta-analysis, and 1 case report) meeting the inclusion criteria were identified. Maternal medication or alcohol use during gestation; lifestyle modifiable maternal pathologies such as obesity, diabetes, or hypertension; lack of prenatal care; and a low socioeconomic status were identified as significant maternal environmental risk factors for CH development. Maternal infections and trauma to the mother during pregnancy have also been highlighted as potential mother-related risk factors for CH. CONCLUSIONS Congenital hydrocephalus is an important cause of serious infant health disability that can lead to health inequalities among adults. The present study identified several maternal environmental risk factors for CH, thus yielding important scientific information relevant to prevention of some CH cases. However, further research is warranted to confirm the impact of the identified factors and examine their underlying behavioral and/or biological basis, leading to the generation of suitable prevention strategies.

Interventions for idiopathic intracranial hypertension.

BACKGROUND: Idiopathic intracranial hypertension (IIH) has an estimated incidence of one to three people per 100,000 people per year, and occurs most commonly in obese, young women. IIH is associated with severe morbidity, notably due to a significant threat to sight and severe headache. Several different management options have been proposed. Conservative measures centre on weight loss. Pharmacological therapy includes use of diuretics. Refractory and sight-threatening cases demand surgical intervention, most often in the form of cerebrospinal fluid (CSF) diversion or optic nerve sheath fenestration. Other treatments include venous sinus stenting and bariatric surgery. OBJECTIVES: To assess the effects of any intervention for IIH in any patient group. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015 Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to July 2015), EMBASE (January 1980 to July 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 22 July 2015. SELECTION CRITERIA: We included only randomised controlled trials (RCTs) in which any intervention was compared to placebo, or to another form of treatment, for people with a clinical diagnosis of IIH. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the search results for trials to be included in the review. We resolved any discrepancies by third party decision. MAIN RESULTS: We identified two completed RCTs (enrolling a total of 211 participants and conducted in the UK and US) and two ongoing trials that met the inclusion criteria. Both completed trials compared acetazolamide to placebo, in conjunction with a weight loss intervention in both groups. Attrition bias was a problem in both trials with high loss to follow-up, in one study this loss to follow-up occurred particularly in the acetazolamide arm. One trial was unmasked and we judged it to be at risk of performance and detection bias.In these studies, change in visual acuity was similar in the treatment and control groups as measured by logMAR acuity. In one study people in the acetalomazide group had a similar change in logMAR acuity compared to the placebo group between baseline and 12 months in the right eye (MD 0.04 logMAR, 95% CI -0.08 to 0.16) and left eye (MD 0.03 logMAR, 95% CI -0.09 to 0.15). In the other study people in the acetalomazide group had a similar change in vision over six months compared with people in the placebo group (mean difference in change in letters read was 0.01 (95% CI -1.45 to 1.46). One study reported no cases of visual loss in 21 people treated with acetalomazide compared to 2/20 cases in the placebo group (odds ratio 0.17, 95% CI 0.01, 3.82).The prespecified outcome for this review was reduction in CSF pressure to normal levels which was not reported by the two trials. One trial reported that, in a subsample of 85 participants who agreed to lumbar puncture at 6 months, people in the acetalomazide group on average had a greater reduction in CSF pressure (MD -59.9 mmH(2)O, 95% CI -96.4, -23.4).In one study, people in the acetalozamide group on average experienced a greater reduction in papilloedema as assessed by fundus photographs MD -0.70 (95% CI -1.00 to -0.40) and by clinical grading MD -0.91 (95% CI -1.27 to -0.54) between baseline and six months in the study eye.Headache was recorded as present/absent in one study at 12 months (OR 0.42, 95% CI 0.12,1.41, 41 participants). Both studies reported headache on visual analogue scales (different ones) but results were inconclusive (MD for change in headache score measured on 10-point visual analogue scale at 12 months was 1.0 (-1.80, 3.70, 41 participants) and MD for change in headache score on a 6 point scale measured at 6 months was -0.45 (-3.5,2.6, number of participants unclear).In one study, a similar proportion of people in the acetalomazide group were in remission (however, the trial authors did not state their definition of this term) at 12 months compared to the placebo group. However, the 95% CIs were wide and there is considerable uncertainty as to the effect (OR 1.13 (95% CI 0.32 to 3.90, 41 participants).In one study of 185 participants, people in the acetalomazide group had an increased risk of decreased CO2, diarrhoea, dysgeusia, fatigue, nausea, paresthesia, tinnitus and vomiting compared to people in the placebo group. In general, the estimates of effect were uncertain with wide 95% CIs. Adverse effects were not reported in the other study.One study reported that quality of life was better in acetazolamide-treated patients based on the visual quality of life (VFQ-25) (MD 6.35, 95% CI 2.22 to 10.47) and the physical (MD 3.02, 95% CI 0.34 to 5.70) and mental (MD 3.45, 95% CI 0.35 to 6.55) components of the 36-Item Short Form Health Survey tool at six months. Costs were not reported in either study.We judged the evidence to be low certainty (GRADE) downgrading for imprecision and risk of bias. AUTHORS' CONCLUSIONS: Although the two included RCTs showed modest benefits for acetazolamide for some outcomes, there is insufficient evidence to recommend or reject the efficacy of this intervention, or any other treatments currently available, for treating people with IIH. Further high-quality RCTs are required in order to adequately assess the effect of acetazolamide therapy in people with IIH.