Clinicopathological Features in Morvan's Syndrome: An Autopsy Case Study.

Morvan's syndrome is a rare, complex autoimmune syndrome comprising peripheral nerve hyperexcitability, dysautonomia, insomnia, and encephalopathy. In this case report, we highlight the clinical and pathological findings of an elderly gentleman who presented to us with clinical features of Morvan's syndrome associated with anti-contactin-associated protein 2 (CASPR-2) antibodies. Histopathology [Figure 3] revealed cortical atrophy with gliosis and mild microglial proliferation. Microglial activation and gliosis were observed in the hippocampus, hypothalamus, and thalamus. Brainstem showed multifocal inflammation. Mild inflammation was observed in the leptomeninges. Morvan's syndrome is an autoimmune disease with antibodies targeted against CASPR within the voltage-gated potassium channel (VGKC) complex. Early diagnosis and treatment play a key role in the management of patients. Most patients show a good response when treated with plasmapheresis and steroids. This patient presented to us late into the illness and succumbed.

Interleukin-31 in serum and cerebrospinal fluid of dogs with syringomyelia.

BACKGROUND: Syringomyelia is a spinal cord cavity containing cerebrospinal fluid (CSF)-like fluid. If syringomyelia asymmetrically involves the dorsal horn grey matter of the spinal cord, affected dogs show increased signs of dysesthesia and neuropathic pain, like increased itching behaviour. In the dorsal horn, amongst others, receptors for Interleukin-31 (IL-31) can be found. IL-31 is one of the main cytokines involved in the pathogenesis of pruritus in atopic dermatitis in different species. This study investigates suspected elevated levels of IL-31 in serum and CSF of dogs showing signs of pain or increased itching behaviour related to syringomyelia. The IL-31 were measured in archived samples (52 serum and 35 CSF samples) of dogs with syringomyelia (n = 48), atopic dermatitis (n = 3) and of healthy control dogs (n = 11) using a competitive canine IL-31 ELISA. RESULTS: Mean serum IL-31 level in dogs with syringomyelia was 150.1 pg/ml (n = 39), in dogs with atopic dermatitis 228.3 pg/ml (n = 3) and in healthy dogs 80.7 pg/ml (n = 10). Mean CSF IL-31 value was 146.3 pg/ml (n = 27) in dogs with syringomyelia and 186.2 pg/ml (n = 8) in healthy dogs. Individual patients with syringomyelia (especially dogs with otitis media or otitis media and interna or intervertebral disc herniation) showed high IL-31 levels in serum and CSF samples, but the difference was not statistically significant. IL-31 serum and CSF levels did not differ significantly in dogs with syringomyelia with or without itching behaviour and with or without signs of pain. CONCLUSION: Based on this study, increased IL-31 levels seem not to be correlated with itching behaviour or signs of pain in dogs with syringomyelia, but might be caused by other underlying diseases.

Impairment of Connexin 43 may initiate cilia decline in syringomyelia.

Ependymal cilia, which are maintained by the Connexin 43 (Cx43) and protected by the actin network, play an essential role in regulating cerebrospinal fluid (CSF) circulation. The decline of ependymal cilia has been reported in syringomyelia, but the underlying mechanism remains unclear. In this study, we used an extradural compression-induced syringomyelia rat model to investigate the changes in cilia and related pathologies during the formation of syringomyelia. We divided rats into control and syringomyelia groups and sacrificed them at three time points, 7, 14, and 28 days postoperative (dpo). Scanning electron microscopy (SEM) and immunofluorescence (IF) were used to illustrate the number and morphology of ependymal cilia. IF was also used to show the status of centrioles, actin network, and Cx43 (the main component of the gap junction). Transmission electron microscopy (TEM) was used to observe the structure of the gap junction. The results showed that most syringomyelia were located at segments (T10-12) rostral to the compression site (T13). SEM images showed that the number of cilia in the central canal (CC) declined in two phases during the development of syringomyelia (early stage, 7 dpo; later stage, 14 and 28 dpo). The number of cilia showed a significant difference between the early and later stages of syringomyelia development. Additionally, TEM showed the absence of gap junction and IF illustrated less Cx43 expression in ependymal cells (ECs) at the compression site in both the early and later stages. Actin network disruption and centrioles reduction at adjacent segments rostral to the compression site were found in the later stage. These findings indicate that the loss of Cx43 at the compression site may be related to cilia detachment at rostral adjacent segments by disrupting intercellular communication in the early stage of syringomyelia development. This early cilia decline then causes actin network disorganization, further aggravating cilia decline by exposing centrioles to CSF shear stress in the later stage. These findings suggest a potential mechanism of ependymal cilia decline in the development of syringomyelia and may provide a novel perspective for future research in this area.

Effectiveness of C1 Laminectomy for Chiari Malformation Type 1: Posterior Fossa Volume Expansion and Syrinx-Volume Decrease Rate.

PURPOSE: This study aimed to analyze the effect of foramen magnum decompression with C1 laminectomy (C1L) for Chiari malformation type 1 (CM-1) in terms of improving clinical symptoms, expanding posterior fossa volume, and decreasing syrinx volume. MATERIALS AND METHODS: Between January 2007 and June 2019, 107 patients with CM-1 were included. The median patient age was 13±13 years (range: 9 months-60 years), female-to-male ratio was 1:1, and average length of tonsil herniation was 13±5 mm (range: 5-24 mm). Surgical techniques were divided into four groups based on duraplasty or C1L usage. Among the study subjects, 38 patients underwent duraplasty and had their syrinx volumes measured separately on serial magnetic resonance imaging. A three-dimensional visualization software was used to evaluate the syrinx-volume decrease rate. RESULTS: Bony decompression exhibited a mere 20% volume expansion of the lower-half posterior fossa. C1L offered a 3% additional volume expansion, which rose to 5% when duraplasty was added (p=0.029). There were no significant differences in complication rate when C1L was combined with duraplasty (p=0.526). Syrinx volumes were analyzed in 38 patients who had undergone duraplasty. Among them, 28 patients who had undergone duraplasty without C1L demonstrated a 5.9% monthly decrease in syrinx volume, which was 7.5% in the remaining 10 patients with C1L (p=0.040). CONCLUSION: C1L was effective in increasing posterior fossa volume expansion, both with and without duraplasty. A more rapid decrease in syrinx volume occurred when C1L was combined with duraplasty.

Dorsal horn volume loss and pain pathway changes in Cavalier King Charles Spaniels with syringomyelia, signs of pain, and phantom scratching.

ABSTRACT: Central neuropathic pain is a core clinical sign of syringomyelia in humans and Cavalier King Charles Spaniel (CKCS) dogs. This histopathological study used spinal cords from CKCS dogs with syringomyelia to investigate the following conditions: (1) whether specific structural cervical spinal cord entities involved in nociception were affected by loss of neuroparenchyma or other pathological changes in CKCS dogs with pain-related behaviour and phantom scratching, (2) whether pain-related behaviour or phantom scratching correlated with loss of a specific anatomical entity or upregulation of glia cells, and (3) whether syringomyelia-related lesions affected specific functional spinal cord units of nociception. Spinal cord segments C1-C8 from CKCS dogs with magnetic resonance imaging-confirmed syringomyelia and clinical signs of pain and phantom scratching (n = 8) were compared with those from CKCS dogs without syringomyelia (n = 4). Dogs with unilateral scratching (n = 7) had a volume loss ( P = 0.043) of the dorsal horn laminae I-III in the ipsilateral side compared with the contralateral dorsal horn. A clear pattern of ipsilateral changes in the dorsal root entry zone characterised by deafferentation and reorganization of first-order axons into deeper laminae was found in cases with lateralised scratching. Significant changes in cell number density were not found for astrocytes or microglia, suggesting that the dogs represented cases of end-stage syringomyelia and thus could not reveal astrogliosis and microgliosis, which may be involved in the early phases of syrinx development and phantom scratching. The present relationship between clinical findings and dorsal horn and pain pathway pathology in CKCS dogs suggests that these dogs may be of interest as a supplement to experimental model pain research.

Effect of mesenchymal stem cells therapy in experimental kaolin induced syringomyelia model.

BACKGROUND: Syringomyelia is a pathological cavitation of the spinal cord. In this study, we examined whether a syrinx cavity would limit itself with axonal regeneration and stem cell activity in the cavity, and we evaluated subjects on a functional basis. METHODS: Groups were designated as kaolin, trauma, kaolin-trauma, and saline groups. Also divided out of the syringomyelia treated groups were those given human mesenchymal stem cells (hMSCs). All groups were evaluated with immunohistochemistry, electron microscopy, confocal microscopy and functionally. RESULTS: The kaolin-trauma group had a significant correction of BBB score with hMSCs therapy. The syrinx cavity measurements showed significant improvement in groups treated with hMSCs. The tissue surrounding the syrinx cavity, however, appeared to be better organized in groups treated with hMSCs. The process of repair and regeneration of damaged axons in the lesion were more improved in groups treated with hMSCs. Using confocal microscopy, fluorescence of hMSCs was observed in the central canal, in the ependymal tissue, and around the lesion. CONCLUSIONS: It was concluded that axonal repair accelerated in groups receiving stem cells, and thus, stem cells may be effective in recovery of neural tissue and myelin damage in syringomyelia.

Long-term surgical outcome of Chiari type-I malformation-related syringomyelia: an experience of tertiary referral hospital.

OBJECTIVE: Syringomyelia is a common condition seen in patients with Chiari type-I malformation (CM1). The purpose of this retrospective study was to evaluate the long-term clinical and radiological outcomes of posterior fossa decompression with duraplasty (PFDD) with coagulation of tonsillar ectopia in consecutive surgically treated adult patients with CM1-related syringomyelia (CRS). METHODS: Over 9 years' duration (1993-2001), medical charts of diagnosed patient with CM1 at our neurosurgical center were reviewed retrospectively. This study included adult patients with CM1 who had syringomyelia and underwent PFDD with coagulation of tonsillar ectopia surgery. The differences between the pre- and postoperative syrinx/cord ratio (S/C), the syrinx length, and the regression of herniated cerebellar tonsils on coronal and midsagittal MRIs were evaluated. RESULTS: A total of 87 surgical procedures (46 primary operations, 7 ventriculoperitoneal shunts, and 34 additional operations) for CRS were performed on 24 males and 22 females. The mean preoperative S/C was 0.59 ± 0.12. The means of regression in herniated cerebellar tonsils on mid-sagittal and coronal images were 11.8 ± 2.3 mm and 10.2 ± 2.2 mm (p < 0.0001), respectively. 35 (76.1%) patients were discharged after showing signs of recovery or improvement. Different complications occurred in 16 (34.8%) patients. Negative correlations were noticed between postoperative recovery/improvement and the long symptoms' duration, the herniated tonsils' extent, S/C, and the persistence of the herniated tonsils on the coronal images. CONCLUSION: Early diagnosis of patients with CRS can improve surgical outcomes. Due to its efficacy in resolving clinical symptoms and syrinx cavities, PFDD is still an optimal surgical approach for CRS.

Statistical Shape Analyses of the Brainstem in Chiari Patients.

AIM: To ascertain whether the brain stem?s shape differs in patients with syrinx and without syrinx in cases with Chiari malformation Type I (CM-1), relative to healthy controls. MATERIAL AND METHODS: Data on marked brainstem regions were obtained from 2D digital image files. Generalized Procrustes analysis was used to evaluate shape differences among patients with syrinx, patients without syrinx, and healthy controls. Shape deformations among groups were examined by Thin Plate Spline (TPS) analysis. RESULTS: According to the brain stem shape, there were differences between patients with syrinx and controls, and between patients without syrinx and controls. High-level deformations were also observed among the groups. CONCLUSION: In the present study, the presence of shape deformations in Chiari patients? brainstem was demonstrated. This is the first study using a landmark-based geometrical morphometric method to demonstrate the shape difference in Chiari patients? brainstem.

Specific microstructural changes of the cervical spinal cord in syringomyelia estimated by diffusion tensor imaging.

The microstructure of the spinal cord in syringomyelia has not been well studied. The aim of this study was to evaluate the microstructure of the cervical cord in patients with syringomyelia using diffusion tensor imaging (DTI) and to investigate the association between DTI parameters and the size of the syrinx cavity. Thirty patients with syringomyelia and 11 age-matched controls were included in this study. DTI and T1/T2-weighted MRI were used to estimate spinal microstructure. The patients were divided into a clinical symptom group (group A) and a non-clinical symptom group (group B) according to ASIA assessments. The fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values (mm2/s) were measured and compared between patients and controls. Correlation between FA/ADC and the size of the syrinx cavity was examined with a bivariate analysis. FA values were lower (P < 0.000) and ADC values were higher (P < 0.000) compared to the controls at the level of all syrinxes examined in patients with syringomyelia; both FA values and ADC values reached normal values either above or below the syrinx levels (all P > 0.05). FA values and ADC values at all cervical levels were not significantly different either in controls or outside of the syrinx (all P > 0.05). FA values of group A was significantly lower than those of group B (P < 0.000). There was a negative association between FA values and the size of syrinx cavity, and a positive association between ADC values and the size of syrinx cavity (FA: P < 0.05, ADC: P < 0.05). The microstructure of the cervical spinal cord is different across all patients with syringomyelia. DTI is a promising tool for estimating quantitative pathological characteristics that are not visible with general MRI.

Presacral neuroendocrine tumors associated with the Currarino syndrome.

Currarino syndrome (CS) is an autosomal dominant syndrome caused by mutations in MNX1 and characterized by anorectal abnormalities, partial sacral agenesis, and presacral masses. The presacral masses are typically benign; however, malignant degeneration can occur, and presacral neuroendocrine tumors (NETs) have been reported in six cases. We report three individuals from two families affected by CS in which multiple individuals developed presacral NETs. The first family, 491, had six members with features of CS, including two siblings who presented with presacral, Grade 2 NETs, one of which had metastasized to bone and lymph nodes. A germline c.874C>T (p.Arg292Trp) mutation was found in a highly conserved region of MNX1 in three affected members who underwent sequencing. A second somatic variant/deletion in MNX1 was not detected in either patient's tumor. In the second family, 342, the proband presented with an incidentally discovered presacral NET. The proband's father had previously undergone resection of a presacral NET, and so genetic testing was performed, which did not reveal an MNX1 mutation or copy number variants. The lack of a second, somatic mutation in the tumors from family 491 argues against MNX1 acting as a tumor suppressor, and the absence of a germline MNX1 mutation in family 342 suggests that other genetic and anatomic factors contribute to the development of presacral NETs. These cases highlight the variable presentation of CS, and the potential for malignancy in these patients.

Transplantation of Human Neural Precursor Cells Reverses Syrinx Growth in a Rat Model of Post-Traumatic Syringomyelia.

Posttraumatic syringomyelia (PTS) is a serious condition of progressive expansion of spinal cord cysts, affecting patients with spinal cord injury years after injury. To evaluate neural cell therapy to prevent cyst expansion and potentially replace lost neurons, we developed a rat model of PTS. We combined contusive trauma with subarachnoid injections of blood, causing tethering of the spinal cord to the surrounding vertebrae, resulting in chronically expanding cysts. The cysts were usually located rostral to the injury, extracanalicular, lined by astrocytes. T2*-weighted magnetic resonance imaging (MRI) showed hyperintense fluid-filled cysts but also hypointense signals from debris and iron-laden macrophages/microglia. Two types of human neural stem/progenitor cells-fetal neural precursor cells (hNPCs) and neuroepithelial-like stem cells (hNESCs) derived from induced pluripotent stem cells-were transplanted to PTS cysts. Cells transplanted into cysts 10 weeks after injury survived at least 10 weeks, migrated into the surrounding parenchyma, but did not differentiate during this period. The cysts were partially obliterated by the cells, and cyst walls often merged with thin layers of cells in between. Cyst volume measurements with MRI showed that the volumes continued to expand in sham-transplanted rats by 102%, while the cyst expansion was effectively prevented by hNPCs and hNESCs transplantation, reducing the cyst volumes by 18.8% and 46.8%, respectively. The volume reductions far exceeded the volume of the added human cells. Thus, in an animal model closely mimicking the clinical situation, we provide proof-of-principle that transplantation of human neural stem/progenitor cells can be used as treatment for PTS.

Hypothesis on the pathophysiology of syringomyelia based on analysis of phase-contrast magnetic resonance imaging of Chiari-I malformation patients.

Background: Despite several hypotheses, our understanding of syringomyelia's pathophysiology remains limited. The hypothesis proposed by Oldfield et al. suggests that piston-like movement of the cerebellar tonsils propels the cerebrospinal fluid (CSF) into the syrinx via the spinal perivascular space. However, a significant question remains unanswered: how does the CSF enter and stay in the syrinx, which has a higher pressure than the subarachnoid space. In the current study, we attempted to verify Oldfield's hypothesis using phase-contrast magnetic resonance imaging (MRI) data from patients with syringomyelia. Methods: We analyzed phase-contrast MRI scans of 18 patients with Chiari-I malformation associated with syringomyelia, all of whom underwent foramen magnum decompression, and 21 healthy volunteers. We obtained velocity waveforms for CSF and brain tissue from regions of interest (ROI) set at the various locations. These waveforms were synchronized at the peak timing of downward CSF flow. We compared the preoperative patient data with the control data and also compared the preoperative patient data with the postoperative patient data. Results: The syrinx shrank in 17 (94%) of the patients, and they experienced significant clinical improvement. When comparing pre- and postoperative MRI results, the only significant difference noted was the preoperative elevated velocity of the cerebellar tonsil, which disappeared post-surgery. The CSF velocities in the subarachnoid space were higher in the preoperative patients than in the controls, but they did not significantly differ in the postoperative MRI. The tonsillar velocity in the preoperative MRI was significantly lower than that of the CSF, suggesting that the elevated tonsillar velocity was more of an effect, rather than the cause, of the elevated CSF velocity. Conclusions: Given these findings, a completely new paradigm seems necessary. We, therefore, propose a novel hypothesis: the generative force of syringomyelia may be the direction-selective resistance to CSF flow in the subarachnoid space.

Rapid deterioration of an asymptomatic lumbosacral lipoma due to formation of an extracanalicular syrinx: case report.

The authors present the case of a 1-month-old girl with a lumbosacral lipoma who then developed an extracanalicular syrinx and experienced rapid deterioration. The patient's initial MRI study, obtained before she became symptomatic, revealed a spinal lipoma with a syrinx in contact with the lipoma-cord interface. She was initially asymptomatic but developed loss of motor function in the left leg 14 days after MRI. Emergency surgery was performed. Intraoperative findings revealed a swollen spinal cord. Lipomatous tissue on the caudal side of the conus was removed subtotally, and the central canal was opened. Expansion of the syrinx was observed intraoperatively. Postoperatively, the patient's left leg paresis remained. Postoperative MRI revealed rostral and extracanalicular expansion of the syrinx. This is the first report on the rapid deterioration of a conus lipoma due to extracanalicular expansion of a syrinx. Careful follow-up and repeat MRI should be considered for patients with spinal lipomas with syringomyelia, especially when the syrinx is attached to the lipoma-cord interface.

Association between craniovertebral junction abnormalities and syringomyelia in patients with chiari malformation type-1.

OBJECTIVE: To assess the correlation between craniovertebral junction (CVJ) abnormalities and syringomyelia in patients with Chiari malformation type-1 (CM1). METHODS: This was a retrospective study including patients with CM1. Identification of cases was done by searching a radiology database at a university hospital from 2012 to 2017. Patients were divided into 2 groups based on whether CVJ abnormalities were present (CVJ+) or absent (CVJ-). The patients` demographic and clinical data were reviewed. All magnetic resonance imaging studies were examined by a certified neuroradiologist. RESULTS: Sixty-four consecutive patients with CM1 were included. The mean age was 24+/-17 years; 59% were females. The CVJ+ group had more female patients (p=0.012). The most frequent CVJ abnormality was platybasia (71%), followed by short clivus (44%) and cervical kyphosis (33%). The CVJ abnormalities were more in Syringomyelia cases (p=0.045). However, the results were not significant when hydrocephalus cases were excluded. CONCLUSION: Among CM1 patients, CVJ abnormalities were found more in patients with syringomyelia. Future studies with larger sample size are required to further study the correlation between CVJ abnormalities and both syringomyelia and hydrocephalus in CM1 patients.

Chronic extradural compression of spinal cord leads to syringomyelia in rat model.

BACKGROUND: Syringomyelia is a common spinal cord lesion. However, whether CSF blockage is linked to the formation and enlargement of syringomyelia is still controversial. The current model of syringomyelia needs modification to more closely mimic the clinical situation. METHODS: We placed cotton strips under the T13 lamina of 40 8-week-old rats and blocked CSF flow by extradural compression. After 4 and 8 weeks, MRI was performed to evaluate the morphology of syringomyelia and the ratio of spinal cord diameter to syrinx diameter calculated. Locomotor function was evaluated weekly. Spinal cord sections, staining and immunohistochemistry were performed 8 weeks after surgery, the ratio of the central canal to the spinal cord area was calculated, and ependymal cells were counted. In another experiment, we performed decompression surgery for 8 rats with induced syringomyelia at the 8th week after surgery. During the surgery, the cotton strip was completely removed without damaging the dura mater. Then, the rats received MRI imaging during the following weeks and were sacrificed for pathological examination at the end of the experiment. RESULTS: Syringomyelia formed in 82.5% (33/40) of rats at the 8-week follow-up. The Basso, Beattie and Bresnahan (BBB) scores of rats in the experimental group decreased from 21.0±0.0 to 18.0 ±3.9 in the first week after operation but returned to normal in later weeks. The BBB score indicated that the locomotor deficit caused by compression is temporary and can spontaneously recover. MRI showed that the syrinx is located in the center of the spinal cord, which is very similar to the most common syringomyelia in humans. The ratio of the central canal to the spinal cord area reached (2.9 ± 2.0) × 10-2, while that of the sham group was (5.4 ± 1.5) × 10-4. The number of ependymal cells lining the central canal was significantly increased (101.9 ± 39.6 vs 54.5 ± 3.4). There was no syrinx or proliferative inflammatory cells in the spinal cord parenchyma. After decompression, the syringomyelia size decreased in 50% (4/8) of the rats and increased in another 50% (4/8). CONCLUSION: Extradural blockade of CSF flow can induce syringomyelia in rats. Temporary locomotor deficit occurred in some rats. This reproducible rat model of syringomyelia, which mimics syringomyelia in humans, can provide a good model for the study of disease mechanisms and therapies.

Intradural Pathology Causing Cerebrospinal Fluid Obstruction in Syringomyelia and Effectiveness of Foramen Magnum and Foramen of Magendie Dredging Treatment.

OBJECTIVE: This article discusses the procedure of foramina magnum and Magendie dredging, summarizing the pathologic changes in the intradural region of the craniocervical junction in patients with syringomyelia and the pathophysiologic mechanism of cerebrospinal fluid (CSF) circulation obstruction. METHODS: Clinical data from 50 adult patients with syringomyelia treated at Xuanwu Hospital from July 2018 to January 2019 were collected and retrospectively analyzed. All operations were performed with foramina magnum and Magendie dredging, and all intradural factors that may have induced the obstruction of CSF circulation were recorded. RESULTS: Intradural pathology was found in all patients. The pathologic changes that may have caused obstruction of the CSF circulation include tonsil occupying the foramen magnum and overlying foramen of Magendie in 88% (44/50), intertonsillar arachnoid adhesions in 36% (18/50), tonsil to medulla arachnoid adhesions in 18% (9/50), medialized tonsils in 70% (35/50), vermian branch of posterior inferior cerebellar artery in 22% (11/50), arachnoid veil in 16% (8/50), cisterna magna cyst in 4% (2/50), and tonsil to dura mater arachnoid adhesions in 8% (4/50). Mean duration of follow-up was 13.3 months. The long-term effective rate was 96.0%. Postoperative magnetic resonance imaging revealed that the size of the syringomyelia was reduced or completely resolved in 88% of patients. The mean preoperative Japanese Orthopaedic Association score was 12.9 ± 3.1, which improved to 14.7 ± 3.2 (P < 0.05) at last clinical follow-up. CONCLUSIONS: Intradural pathology that causes CSF circulation obstruction exists in many forms. Relieving the obstruction of the foramen magnum and foramen of Magendie is key to surgical treatment.

Nonreflecting Boundary Conditions for a CSF Model of Fourth Ventricle: Spinal SAS Dynamics.

In this paper, we introduce a one-dimensional model for analyzing the cerebrospinal fluid dynamics within the fourth ventricle and the spinal subarachnoid space (SSAS). The model has been derived starting from an original model of Linninger et al. and from the detailed mathematical analysis of two different reformulations. We show the steps of the modelization and the rigorous analysis of the first-order nonlinear hyperbolic system of equations which rules the new CSF model, whose conservative-law form and characteristic form are required for the boundary conditions treatment. By assuming sub-critical flows, for the particular dynamics we are dealing with, the most desirable option is to employ the nonreflecting boundary conditions, that allow the simple wave associated with the outgoing characteristic to exit the computational domain with no reflections. Finally, we carry out some numerical simulations related to different cerebral physiological conditions.