Tag: pathophysiology

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Is there a relationship between the extent of tonsillar ectopia and the severity of the clinical Chiari syndrome?

Acta Neurochirurgica (2020) 162:1531–1538

Chiari 1 malformation is diagnosed if the cerebellar tonsils extend at least 5 mm below the opisthion-basion line.

Objective To examine the correlation of the extent of tonsillar ectopia with the prevalence and severity of the symptoms associated with the Chiari malformation.

Methods Patients (N = 428) were grouped according to the extent of tonsillar ectopia on the mid-sagittal MRI image (group 1, 0–< 3 mm; group 2, 3–5 mm; group 3, > 5 mm). Groups were compared regarding demographics, symptoms, neurological signs, pain score, and response to HADS and sf-36 questionnaires.

Results were analyzed using one-way ANOVA, chi-square, and two sample Z test, and Student’s t test for pairwise comparison, (statistical significance p < 0.05). A logistic regression analysis was performed to determine the relationship between tonsillar ectopia and the probability of a patient reporting any particular symptom. Results There were 97,148 and 183 patients in groups 1, 2, and 3 respectively. Groups did not differ with regard to antecedent trauma or female preponderance. Patients in group 1 were more symptomatic than those in groups 2 and 3 with regard to some symptoms, (p = 0.04–p = 0.000). Regression analysis confirmed an inverse relationship between the extent of tonsillar ectopia and the likelihood of many symptoms. The pain score was greatest in group 1, (p = 0.006). Prevalence of objective signs of myelopathy did not differ between groups except for Hoffmann sign which was more prevalent in group 1, (p = 0.034). HADS and sf-36 scores did not differ between groups.

Conclusion The severity of the symptoms associated with the Chiari malformation does not correlate directly with the extent of tonsillar ectopia. The extent of tonsillar ectopia should be re-evaluated as the threshold for diagnosis of Chiari 1 malformation.

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Is there a relationship between the extent of tonsillar ectopia and the severity of the clinical Chiari syndrome?

Acta Neurochirurgica (2020) 162:1531–1538

Chiari 1 malformation is diagnosed if the cerebellar tonsils extend at least 5 mm below the opisthion-basion line. Objective To examine the correlation of the extent of tonsillar ectopia with the prevalence and severity of the symptoms associated with the Chiari malformation.

Methods Patients (N = 428) were grouped according to the extent of tonsillar ectopia on the mid-sagittal MRI image (group 1, 0–< 3 mm; group 2, 3–5 mm; group 3, > 5 mm). Groups were compared regarding demographics, symptoms, neurological signs, pain score, and response to HADS and sf-36 questionnaires. Results were analyzed using one-way ANOVA, chi-square, and two sample Z test, and Student’s t test for pairwise comparison, (statistical significance p < 0.05). A logistic regression analysis was performed to determine the relationship between tonsillar ectopia and the probability of a patient reporting any particular symptom.

Results There were 97,148 and 183 patients in groups 1, 2, and 3 respectively. Groups did not differ with regard to antecedent trauma or female preponderance. Patients in group 1 were more symptomatic than those in groups 2 and 3 with regard to some symptoms, (p = 0.04–p = 0.000). Regression analysis confirmed an inverse relationship between the extent of tonsillar ectopia and the likelihood of many symptoms. The pain score was greatest in group 1, (p = 0.006). Prevalence of objective signs of myelopathy did not differ between groups except for Hoffmann sign which was more prevalent in group 1, (p = 0.034). HADS and sf-36 scores did not differ between groups.

Conclusion The severity of the symptoms associated with the Chiari malformation does not correlate directly with the extent of tonsillar ectopia. The extent of tonsillar ectopia should be re-evaluated as the threshold for diagnosis of Chiari 1 malformation.

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The pathophysiology of chronic noncommunicating hydrocephalus: lessons from continuous intracranial pressure monitoring and ventricular infusion testing

J Neurosurg 129:220–233, 2018

The pathophysiology of chronic noncommunicating hydrocephalus (ncHC) is poorly understood. This present study explored whether lessons about the pathophysiology of this clinical entity might be retrieved from results of overnight monitoring of pulsatile and static intracranial pressure (ICP) and ventricular infusion testing.

METHODS The study cohort included adult patients (> 20 years of age) with chronic ncHC due to aqueductal stenosis in whom symptoms had lasted a minimum of 6 months. A reference cohort consisted of age- and sex-matched patients managed for communicating HC (cHC). Information about symptoms and clinical improvement following surgery was retrieved from a quality register, and results of overnight ICP recordings and ventricular infusion testing were retrieved from the hospital ICP database.

RESULTS The cohort with ncHC consisted of 61 patients of whom 6 (10%) were managed conservatively, 34 (56%) by endoscopic third ventriculostomy (ETV), and 21 (34%) using ETV and subsequent shunt surgery. In patients responding to surgery, pulsatile ICP (mean ICP wave amplitude) was significantly increased to a similar magnitude in patients with ncHC and the reference cohort (cHC). Furthermore, intracranial compliance (ICC) was reduced in clinical responders. The results of ventricular infusion testing provided evidence that patients responding to ETV have impaired ventricular CSF absorption, while those requiring shunt placement after ETV present with impaired CSF absorption both in the intraventricular and extraventricular compartments.

CONCLUSIONS The study may provide some lessons about the pathophysiology of chronic ncHC. First, increased pulsatile ICP and impaired ICC characterize patients with chronic ncHC who respond clinically to CSF diversion surgery, even though static ICP is not increased. Second, in patients responding clinically to ETV, impaired ventricular CSF absorption may be a key factor. Patients requiring shunt placement for clinical response appear to have both intraventricular and extraventricular CSF absorption failure. A subgroup of patients with ncHC due to aqueductal stenosis has normal ventricular CSF absorption and normal ICC and may not be in need of surgical CSF diversion.

 

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Role of the petrous ridge and angulation of the trigeminal nerve in the pathogenesis of trigeminal neuralgia, with implications for microvascular decompression

Acta Neurochirurgica (2018) 160:971–976

Vascular compression is the main pathogenetic factor in apparently primary trigeminal neuralgia; however some patients may present with clinically classical neuralgia but no vascular conflict on MRI or even at surgery. Several factors have been cited as alternative or supplementary factors that may cause neuralgia. This work focuses on the shape of the petrous ridge at the point of exit from the cavum trigeminus as well as the angulation of the nerve at this point.

Methods Patients with trigeminal neuralgia that had performed a complete imagery workup according to our protocol and had microvascular decompression were included as well as ten controls. In all subjects, the angle of the petrous ridge as well as the angle of the nerve on passing over the ridge were measured. These were compared from between the neuralgic and the nonneuralgic side and with the measures performed in controls.

Results In 42 patients, the bony angle of the petrous ridge was measured to be 86° on the neuralgic side, significantly more acute than that of controls (98°, p = 0.004) and with a trend to be more acute than the non-neuralgic side (90°, p = 0.06). The angle of the nerve on the side of the neuralgia was measured to be on average 141°, not significantly different either from the other side (144°, p=0.2) or from controls (142°, p = 0.4). However, when taking into account the grade of the conflict, the angle was significantly more acute in patients with grade II/III conflict than on the contralateral side, especially when the superior cerebellar artery was the conflicting vessel.

Conclusion This pilot study analyzes factors other than NVC that may contribute to the pathogenesis of the neuralgia. It appears that aggressive bony edges may contribute—at least indirectly—to the neuralgia. This should be considered for surgical indication and conduct of surgery when patients undergo MVD.

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Pathophysiology of Intracranial Aneurysm: The ICAN Project

Neurosurgery 80:621–626, 2017

Understanding the pathophysiologic mechanism of intracranial aneurysm
 (IA) formation is a prerequisite to assess the potential risk of rupture. Nowadays, there are neither reliable biomarkers nor diagnostic tools to predict the formation or the evolution of IA. Increasing evidence suggests a genetic component of IA but genetics studies have failed to identify genetic variation causally related to IA.

OBJECTIVE: To develop diagnostic and predictive tools for the risk of IA formation and rupture.

METHODS: The French ICAN project is a noninterventional nationwide and multicentric research program. Each typical IA of bifurcation will be included. For familial forms, further IA screening will be applied among first-degree relatives. By accurate phenotype description with high-throughput genetic screening, we aim to identify new genes involved in IA. These potential genetic markers will be tested in large groups of patients. Any relevant pathway identified will be further explored in a large cohort of sporadic carriers of IA, which will be well documented with clinical, biological, and imaging data.

EXPECTED OUTCOMES: Discovering genetic risk factors, better understanding the pathophysiology, and identifying molecular mechanisms responsible for IA formation will be essential bases for the development of biomarkers and identification of therapeutic targets.

DISCUSSION: Our protocol has many assets. A nationwide recruitment allows for the inclusion of large pedigrees with familial forms of IA. It will combine accurate phenotyping and comprehensive imaging with high-throughput genetic screening. Last, it will enable exploiting metadata to explore new pathophysiological pathways of interest by crossing clinical, genetic, biological, and imaging information.

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The role of cancer stem cells in glioblastoma

The role of cancer stem cells in glioblastoma

Neurosurg Focus 37 (6):E6, 2014

Recurrence in glioblastoma is nearly universal, and its prognosis remains dismal despite significant advances in treatment over the past decade. Glioblastoma demonstrates considerable intratumoral phenotypic and molecular heterogeneity and contains a population of cancer stem cells that contributes to tumor propagation, maintenance, and treatment resistance. Cancer stem cells are functionally defined by their ability to self-renew and to differentiate, and they constitute the diverse hierarchy of cells composing a tumor. When xenografted into an appropriate host, they are capable of tumorigenesis.

Given the critical role of cancer stem cells in the pathogenesis of glioblastoma, research into their molecular and phenotypic characteristics is a therapeutic priority.

In this review, the authors discuss the evolution of the cancer stem cell model of tumorigenesis and describe the specific role of cancer stem cells in the pathogenesis of glioblastoma and their molecular and microenvironmental characteristics. They also discuss recent clinical investigations into targeted therapies against cancer stem cells in the treatment of glioblastoma.

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Pathophysiology of shunt dysfunction in shunt treated hydrocephalus

Pathophysiology of shunt dysfunction in shunt

Acta Neurochir (2013) 155:1763–1772

We hypothesized that shunt dysfunction in the ventricular catheter and the shunt valve is caused by different cellular responses. We also hypothesized that the cellular responses depend on different pathophysiological mechanisms.

Methods Removed shunt material was collected. Macroscopic tissue in the catheters was paraffin-embedded and HE-stained. Valves were incubated with trypsin-EDTA in order to detach macroscopically invisible biomaterial, which was then cytospinned and HE-stained. Associated aetiological and surgical data were collected by reviewing patient files, and ventricular catheter position was examined using preoperative radiology (CT scans).

Results We examined eleven ventricular catheters and ten shunt valves. Catheters: 6/11 catheters contained intraluminal tissue consisting of vascularised glial tissue and inflammatory cells (macrophages/giant cells and a few eosinophils). Catheter adherence correlated with the presence of intraluminal tissue, and all tissue containing catheters had some degree of ventricle wall contact. All obstructed catheters contained intraluminal tissue, except one catheter that was dysfunctional because of lost ventricular contact. Valves: Regardless of intraoperative confirmation of valve obstruction, all ten valves contained an almost uniform cellular response of glial cells (most likely ependymal cells), macrophages/giant cells, and lymphomonocytic cells. Some degree of ventricle wall catheter contact was present in all examined valves with available radiology (9/10).

Conclusions The same cellular responses (i.e., glial cells and inflammatory cells) cause both catheter obstruction and valve obstruction. We propose two synergistic pathophysiological mechanisms. (1) Ventricle wall/parenchymal contact by the catheter causesmechanical irritation of the parenchyma including ependymal exfoliation. (2) The shunt material provokes an inflammatory reaction, either nonspecific or specific. In combination, these mechanisms cause obstructive tissue ingrowth (glial and inflammatory) in the catheter and clogging of the valve by exfoliated glial cells and reactive inflammatory cells.

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Spinal cord traction, vascular compromise, hypoxia, and metabolic derangements in the pathophysiology of tethered cord syndrome

Neurosurg Focus 29 (1):E9, 2010. (10.3171/2010.3.FOCUS1085)

The definition of tethered cord syndrome (TCS) relies mainly on radiological criteria and clinical picture. The presence of a thickened filum terminale and a low-lying conus medullaris in symptomatic patients is indicative of TCS. The radiological definition of TCS does not take into account cases that involve a normal-lying conus medullaris exhibiting symptoms of the disease.

Methods. The authors performed a MEDLINE search using the terms “tethered cord” and “pathophysiology.” The search returned a total of 134 studies. The studies were further filtered to identify mostly basic research studies in animal models or studies related to the biomechanics of the filum terminale and spinal cord.

Results. Spinal cord traction and the loss of filum terminale elasticity are the triggers that start a cascade of events occurring at the metabolic and vascular levels leading to symptoms of the disease. Traction on the caudal cord results in decreased blood flow causing metabolic derangements that culminate in motor, sensory, and urinary neurological deficits. The untethering operation restores blood flow and reverses the clinical picture in most symptomatic cases.

Conclusions. Although classically defined as a disease of a low-lying conus medullaris, the pathophysiology of TCS is much more complex and is dependent on a structural abnormality, with concomitant altered metabolic and vascular sequelae. Given the complex mechanisms underlying TCS, it is not surprising that the radiological criteria do not adequately address all presentations of the disease.

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