Isotropic volumetric MRI for displaying cranial perineural spread of cranial nerve in nasopharyngeal carcinoma

Objective To observe the value of isotropic volumetric MRI for displaying perineural spread(PNS)of cranial nerve(CN)in nasopharyngeal carcinoma.Methods Eighty-seven patients with pathologically proven nasopharyngeal carcinoma were prospectively enrolled.MR scanning,including three-dimensional liver acquisition with volume acceleration-flexible(3D LAVA_Flex)image,T2WI with fat suppression(T2WI-FS),T1WI,contrast enhancement(CE)T1WI-FS of nasopharynx and neck region were performed.The displaying rates of CN PNS were evaluated and compared between 3D LAVA_Flex and T2WI-FS,T1WI,CE-T1WI-FS at patient level,CN group level and neural level,respectively.Results The displaying rate of CN PNS in all 87 nasopharyngeal carcinoma patients by 3D LAVA_Flex sequence was 49.43%(43/87),higher than that of conventional MRI(30/87,34.48%,P=0.001).Among 59 patients with advanced nasopharyngeal carcinoma diagnosed with conventional sequences,the displaying rate of CN PNS was 71.19%(42/59)by 3D LAVA-Flex sequence,higher than that of conventional MRI(30/59,50.85%,P=0.001).At both patient level and posterior CN level,significant differences of the displaying rate of CN PNS were found between 3D LAVA-Flex sequence and T2WI-FS,T1WI,CE-T1WI-FS,while at CN level,the displaying rates of mandibular nerve PNS,CNⅨ—ⅪPNS in jugular foramen(P<0.05)and CNⅨ—ⅫPNS in carotid space of 3D LAVA_Flex sequence were all significantly higher than that of T2WI-FS,T1WI and CE-T1WI-FS(all P<0.05),of PNS of CNⅢ—Ⅴin cavernous sinus were higher than that of T2WI-FS(P<0.05),while of PNS of hypoglossal nerve were significantly higher than that of T2WI-FS and T1WI(both P<0.05).Conclusion 3D LAVA_Flex sequence could be used to effectively display CN PNS of nasopharyngeal carcinoma.

Skull Base Osteomyelitis: A Rare Cause of Multiple Cranial Nerve Palsies—A Case Report from Ghana

Introduction: Skull Base Osteomyelitis (SBO) is an infectious inflammation of the skull bones that is often caused by malignant otitis externa (MOE) and affects the temporal bone. This condition commonly affects immunocompromised individuals and the elderly, particularly those with a history of diabetes mellitus. Diagnosis is challenging because of non-specific symptoms that lead to late detection and complications. This report discusses a case of SBO with multiple bilateral cranial nerve abnormalities and highlights the diagnostic and management challenges in high-risk individuals with subtle clinical signs. Case presentation: This report describes a 63-year-old patient with hypertension and diabetes who underwent surgical debridement of the left ear due to malignant otitis externa 4 months prior to presentation. The patient presented with significant dysarthria, dysphagia, ptosis of the left eye with double vision, and hearing impairment in the left ear. Examination revealed bilateral CN VI palsy, right CN VII palsy, left CN VIII palsy, and a right CN XII deficit. Initial tests were unremarkable, but a high Fungitell assay and a second review of the CT scan and MRI revealed a pathological process in the base of the skull involving bony structures and cranial nerves bilaterally, which helped diagnose SBO. The patient was subsequently discharged with oral voriconazole and continued his usual medications. The patient requested further management abroad, because he did not notice resolution of his symptoms. Surgical treatment was employed abroad to relieve his symptoms, as he recovered slowly. Conclusion: This case report underscores the importance of a multidisciplinary approach to address SBO. Collaboration between specialists in infectious diseases, otolaryngology, radiology, and neurology plays a pivotal role in achieving an accurate diagnosis and developing a tailored treatment plan. Although SBO may be infrequent, this case report highlights the need to maintain heightened clinical suspicion in high-risk individuals.

Hepatocellular carcinoma metastasizing to the skull base involving multiple cranial nerves

We describe a rare case of HCV-related recurrent multiple hepatocellular carcinoma （HCC） metastasizing to the skull base involving multiple cranial nerves in a 50-year-old woman. The patient presented with symptoms of ptosis, fixation of the right eyeball, and left abducens palsy, indicating disturbances of the right oculomotor and trochlear nerves and bilateral abducens nerves. Brain contrast-enhanced computed tomography （CT） revealed an ill-defined mass with abnormal enhancement around the sella turcica. Brain magnetic resonance imaging （HR/） disclosed that the mass involved the clivus, cavernous sinus, and petrous apex. On contrast-enhanced HRI with gadolinium-chelated contrast medium, the mass showed inhomogeneous intermediate enhancement. The diagnosis of metastatic HCC to the skull base was made on the basis of neurological findings and imaging studies including CT and MRI, without histological examinations, Further studies may provide insights into various methods for diagnosing HCC metastasizing to the craniospinal area.

THE RELATIONSHIP BETWEEN THE INVASION OF PARAPHARYNGEAL SPACES AND THE INVOLVEMENT OF CERVICAL NODES AND POSTERIOR GROUP CRANIAL NERVES IN NASOPHARYNGEAL CARCINOMA

Two hundred cates of nasopharyngeal carcinoma (NPC) admitted to this department from Feb. 1985 to May. 1988 were analysed according to the CT scanning and clinical findings of the primary lesions prior to radiotherapy. The results showed that involvement of parapharyngeal space was very common in NPC, about 80% (160/200 cases) ; particularly unilateral or bilateral retro-styloid spaces, about 69.5% (139/200 cases). It was proposed that patients with NPC had a high Incidence of ipsilateral cervical node metastasis. Contralateral cervical node metastasis was rare. The development of cervical node metastasto in NPC has two modes: one Is direct Infiltration of the retro-stylold space by the lesion; the other Is along the nasopharyngeal lymphatic rete. The data also showed that patients with NPC who presented symptoms of Ⅸ- Ⅲ cranial nerve paralyses always had ipsilateral or bilateral retro- styloid space Infiltrations.

Clinical Application of Quantitative Nursing for Lower Cranial Nerves Injury after Cerebellopontine Angle Tumors

Objective: To retrospectively analyze the clinical utility of quantitative nursing measures of 10 cases of lower cranial nerves injury after cerebellopontine angle tumors surgery to provide the experience for improving the recovery rate and living quality of these patients. Methods: The clinical data of 10 cases of lower cranial nerves injury after cerebellopontine angle tumors surgery was analyzed. For problems such as dysphagia and dyspnea of these patients, the nursing care focused on strict monitoring, timely oxygen inhalation nursing, posture nursing, ventilator nursing, swallowing function training, etc. Results: After received quantitative care, 10 patients with lower cranial nerves injury after cerebellopontine angle tumors surgery were recovered well, and their symptoms such as dysphagia and dyspnea were gradually improved and safely discharged. Conclusion: Lower cranial nerves injury is one of the serious complications after removal of cerebellopontine angle tumors, which impacts the life and health of patients. Caregivers should accurately understand and analyze the symptoms, and quantitative and targeted nursing measures for posterior cranial nerves injury are helpful in the postoperative rehabilitation of patients and improve their living quality.

Multiple cranial nerve palsies with small angle exotropia following COVID-19 mRNA vaccination in an adolescent:A case report

BACKGROUND Several vaccines against the severe acute respiratory syndrome coronavirus 2 have been approved and widely distributed,raising public concerns regarding the side effects of immunization,as the incidence of ease.Although many adverse events following the coronavirus disease 2019(COVID-19)vaccine have been reported,neurological complications are relatively uncommon.Herein,we report a rare case of multiple cranial palsies following COVID-19 vaccination in an adolescent patient.CASE SUMMARY A previously healthy,14-year-old Asian girl with facial palsy presented to the emergency department with inability to close the right eye or wrinkle right side of the forehead,and pain in the right cheek.She had received second dose of the COVID-19 mRNA vaccine(Pfizer-BioNTech)18 days before onset of symptoms.She was diagnosed with Bell’s palsy and prescribed a steroid(1 mg/kg/day methylprednisolone)based on symptoms and magnetic resonance imaging findings.However,the next day,all sense of taste was lost with inability to swallow solid food;the gag reflex was absent.Horizontal diplopia was also present.Due to worsening of her condition,she was given high-dose steroids(1g/day methylprednisolone)for 3 days and then discharged with oral steroids.Improvement in the symptoms was noted 4 days post steroid treatment completion.At the most recent follow-up,her general condition was good with no symptoms except diplopia;ocular motility disturbances were noted.Hence,prism glasses were prescribed for diplopia relief.CONCLUSION Small-angle exotropia was observed in the facial,trigeminal,and glossopharyngeal nerve palsies,in our patient.The etiology of this adverse effect following vaccination was thought to be immunological.

Neck pain and absence of cranial nerve symptom are clues of cervical myelopathy mimicking stroke:Two case reports

BACKGROUND Cervical myelopathy is a potential stroke imitator,for which intravenous thrombolysis would be catastrophic.CASE SUMMARY We herein present two cases of cervical myelopathy.The first patient presented with acute onset of right hemiparesis and urinary incontinence,and the second patient presented with sudden-onset right leg monoplegia.The initial diagnoses for both of them were ischemic stroke.However,both of them lacked cranial nerve symptom and suffered neck pain at the beginning of onset.Their cervical spinal cord lesions were finally confirmed by cervical computed tomography.A literature review showed that neck pain and absence of cranial nerve symptom are clues of cervical myelopathy.CONCLUSION The current report and the review remind us to pay more attention to these two clues in suspected stroke patients,especially those within the thrombolytic time window.

Sellar Chordoma Presenting as Pseudo-macroprolactinoma with Unilateral Third Cranial Nerve Palsy

We described a 61-year-old female with a sellar chordoma, which presented as pseudo-macroprolactinoma with unilateral third cranial nerve palsy. Physical examination revealed that her right upper lid could not be raised by itself, right eyeball movement limited to the abduction direction, right pupil dilated to 4.5 mm with negative reaction to light, and hemianopsia in bitemporal sides. CT scanning showed a hyperdense lesion at sellar region without bone destruction. Magnetic resonance imaging （MRI） revealed the tumor was 2.3 cmx2.8 cmx2.6 cm, with iso-intensity on TlWl, hyper-intensity on T2WI and heterogeneous enhancement on contrast imaging. Endocrine examination showed her serum prolactin level increased to 2,032.49 mlU/ml. The tumor was sub-totally resected via pterional craniotomy under microscope and was histologically proven to be a chordoma. Postoperatively, she recovered uneventfully but ptosis and hemianopsia remained at the 6th month.

Metaphysical Energy Therapy in the Treatment of Cranial Nerve Palsies with Special Reference to Bell’s Palsy

Neuropathy, or nerve injury, is a severe and common impediment of diabetes. Studies evaluate that 50% of people with diabetes will develop neuropathy. Diabetic nerve injury is impairment of a single solitary nerve (also named mononeuropathy). Com- monly 2 cranial nerves Viz., cranial nerve VII and cranial nerve VI are involved in facial nerve palsies. The former one is called Bell’s palsy and is acute Lower Motor Neuron facial nerve paralysis (>80%) causing an inability to control facial muscles on the affected side. The later one is sixth nerve palsy, (the abducens nerve), which is responsible for triggering contraction of the lateral rectus muscle to abduct (i.e., turn out) the eye resulting in double vision on the affected side. In recent times, we have found to our amazement, rapid restoration of normalcy within a few hours to a few days, of Cranial Nerve palsies in diabetic subjects at our centre. We are presenting a group of cases having Type2DM over different time periods from 6 to 20 years and those who suddenly suffered facial nerve palsy and they came to VHSDRC for treatment. They were started on the new modality called the Dynamic Acupuncture Mediated Meta-physical Energy Therapy (DAMM Therapy), to recover from the facial palsy. The DAMM therapy is a unique novel way of infusing and transferring healing energy from the therapist to the patient. Within 2 - 7 sittings of DAMM therapy patients showed 75% - 100% improvement in their clinical condition.

Multiple Cranial Nerve Palsies in Otolaryngology Consultation: An Atypical Clinical Presentation Revealing Myasthenia Gravis

Introduction: Myasthenia gravis is a chronic autoimmune neuromuscular disease, presents with weakness and fatigability of striated skeletal muscles. It is a rare disease in Cameroon. We report an uncommon case of myasthenia gravis in a patient with feeding difficulties, notion of oronasal reflux and swallowing disorders as first complaints. Observation: We report the case of a 29-year-old woman consulted at our department of Otolaryngology and Cervico-Facial Surgery for dysphagia and swallowing disorders. She also presented with facial diplegia, oculomotor paralysis, nasal voice, and dysarthria which has been evolving for several years now. The clinical examination revealed multiple cranial nerve palsies. The complementary workup showed a decrement of more than 50% in the electroneuromyography and the presence of anti-acetylcholine receptor autoantibodies in the blood workup. A diagnosis of myasthenia confirms clinical presumption. We initially observed a worsening of neuromuscular disorders despite the pyridostigmine treatment and subsequently a clear improvement of the clinical features concerning swallowing and speech disorders, oculomotricity and facial diplegia under a treatment combining prednisone and azathioprine. Conclusion: Myasthenia gravis is a rare and potentially fatal autoimmune neuromuscular disease. We thus highlight the atypical clinical presentation and therapeutic itinerary of our patient and the importance to think about this clinical diagnosis in front of any multiple cranial nerve paralysis in otolaryngology consultation.

Imaging traumatic facial nerve injuries:a narrative review of current strategies and future directions for cranial nerve imaging

Traumatic facial nerve injuries can result in temporary or permanent loss of function.Restoration of facial expression may occur spontaneously or require surgical intervention.Although thorough examination and history can localize the site of facial nerve damage,it can be difficult to predict if and when recovery will occur.This is salient because the window for optimal outcomes from surgical re-neurotization can be as short as 1 to 2 years,after which functional loss may be irreversible.It is essential to offer patients the most appropriate treatment plan based on prognosis,and imaging plays an essential role in localizing the site and morphology of nerve injury.Multiple imaging modalities have been used to evaluate the facial nerve,including computed tomography(CT)and,more recently,advanced magnetic resonance imaging(MRI)and ultrasound(US).CT and MRI are more commonly implemented;however,Diffusion tensor tractography,high-resolution US,and functional US are gaining traction for studying cranial nerve pathology.Until recently,the morphology of facial nerve and other cranial nerve injuries could only be inferred using non-invasive diagnostic techniques.With the advent of newer imaging technologies and techniques to examine nerves,more refined assessment and prognostic information is now possible.This article reviews up-to-date cranial nerve imaging techniques from the last ten years and explores future avenues for facial nerve imaging.

Three-dimensional-fast imaging employing steady-state acquisition and T2-weighted fast spin-echo magnetic resonance sequences on visualization of cranial nerves Ⅲ-Ⅻ

Because of the small diameter and complex anatomic course of the cranial nerves except for the optic nerve, trigeminal nerve, facial nerve, and cochlear and vestibular nerve, other cranial nerves are difficult to be visualized in magnetic resonance imaging （MRI） scanning with conventional thickness （5-10 mm）. With the rapid development of MRI technology high spatial resolution, three-dimensional and two-dimensional magnetic resonance imaging technologies have been used in recent years in the observation of normal and abnormal cranial nerves, including three-dimensional constructive interference in steady state （3D CISS） sequence, three- dimensional magnetization-prepared rapid gradient-echo （3D MP-RAGE） sequence, three-dimensional fast inflow with steady-state precession （3D FISP） seohuence, and some fast spin-echo （FSE） sequences. - Threedimensional fast imaging employing steady-state acquisition （3D-FIESTA） is a fast three-dimensional steady-state imaging sequence with high spatial resolution and contrast between the organizational structures. And this sequence was reportedly used in the study on the diseases in the cerebellopontine angle; inner ear and posterior fossa tumors.7＇8 However, the reports about the value of 3D-FIESTA sequence for the visualization of normal cranial nerves are still rare.

Ocular cranial nerve palsies secondary to sphenoid sinusitis

Objective:The clinical presentation of sphenoid sinusitis can be highly variable.Rarely,sphenoid sinusitis may present with cranial nerve complications due to the proximity of these structures to the sphenoid sinus.Method:A case series from Rabin Medical Center and all cases of cranial nerves palsies secondary to sphenoid sinusitis that have been reported in the literature were reviewed.Results:Seventeen patients were identified.The abducent nerve was the most common cranial nerve affected (76％),followed by the oculomotor nerve (18％).One patient had combined oculomotor,trochlear and abducent palsies.The most common pathology was isolated purulent sphenoid sinusitis in 64％ followed by allergic fungal sinusitis (AFS) in 18％,and fungal infection in 18％.94％ had an acute presentation.The majority (85％) received a combined intravenous antibiotics and surgical treatment.The remainder received conservative treatment alone.Complete recovery of cranial nerve palsy was noted in 82％ during follow up.Conclusion:Sphenoid sinusitis presenting as diplopia and headaches is rare.A neoplastic process must be ruled out and early surgical intervention with intravenous antimicrobial therapy carry an excellent outcome with complete resolution of symptoms.

Efficacy of intraorbital electroacupuncture for diabetic abducens nerve palsy： study protocol for a prospective single-center randomized controlled trial

Abducens nerve palsy（ANP） is commonly seen in patients with diabetes mellitus. The validity of acupuncture as a traditional Chinese medicine method in peripheral nerve repair is well established. However, its efficacy in randomized controlled trials remains unclear. Herein, we designed a protocol for a prospective, single-center, randomized controlled trial to investigate the effect of intraorbital electroacupuncture on diabetic ANP. We plan to recruit 60 patients with diabetic ANP, and randomly divide them into treatment and control groups. Patients in both groups will continue their glucose-lowering therapy. A neural nutrition drug will be given to both groups for six weeks. The treatment group will also receive intraorbital electroacupuncture therapy. We will assess efficacy of treatment, eyeball movement, diplopia deviation and the levels of fasting blood-glucose and glycosylated hemoglobin before treatment at 2, 4, and 6 weeks after treatment. The efficacy and recurrence will be investigated during follow-up（1 month after intervention）. This protocol was registered at Chinese Clinical Trial Registry on 16 January 2015（Chi CTR-IPR-15005836）. This study was approved by the Ethics Committee of First Affiliated Hospital of Harbin Medical University of China（approval number： 201452）. All protocols will be in accordance with Declaration of Helsinki, formulated by the World Medical Association. Written informed consent will be provided by participants. We envisage that the results of this clinical trial will provide evidence for promoting clinical use of this new therapy for management of ANP.

Electrical stimulation promotes regeneration of injured oculomotor nerves in dogs

Functional recovery after oculomotor nerve injury is very poor. Electrical stimulation has been shown to promote regeneration of injured nerves. We hypothesized that electrical stimulation would improve the functional recovery of injured oculomotor nerves. Oculomotor nerve injury models were created by crushing the right oculomotor nerves of adult dogs. Stimulating electrodes were positioned in both proximal and distal locations of the lesion, and non-continuous rectangular, biphasic current pulses （0.7 V, 5 Hz） were administered 1 hour daily for 2 consecutive weeks. Analysis of the results showed that electrophysiological and morphological recovery of the injured oc- ulomotor nerve was enhanced, indicating that electrical stimulation improved neural regeneration. Thus, this therapy has the potential to promote the recovery of oculomotor nerve dysfunction.

Management of an intracranial hypotension patient with diplopia as the primary symptom:A case report

BACKGROUND Intracranial hypotension(IH)is a disorder involving cerebrospinal fluid(CSF)hypovolemia due to spontaneous or traumatic spinal CSF leakage and is easily being misdiagnosed or missed,especially in these patients without the prototypical manifestation of an orthostatic headache.At present,the management of IH with both cranial nerve VI palsy and bilateral subdural hematomas(SDHs)is still unclear.CASE SUMMARY A 67-year-old male Chinese patient complained of diplopia on the left side for one and a half mo.Computed tomography revealed bilateral SDHs and a midline shift.However,neurotrophic drugs were not effective,and 3 d after admission,he developed a non-orthostatic headache and neck stiffness.Enhanced magnetic resonance imaging revealed dural enhancement as an additional feature,and IH was suspected.Magnetic resonance myelography was then adopted and showed CSF leakage at multiple sites in the spine,confirming the diagnosis of having IH.The patient fully recovered following multiple targeted epidural blood patch(EBP)procedures.CONCLUSION IH is a rare disease,and to the best of our knowledge,IH with diplopia as its initial and primary symptom has never been reported.In this study,we also elucidated that it could be safe and effective to treat IH patients with associated cranial nerve VI palsy and bilateral SDHs using repeated EBP therapy.

A standardized method to create peripheral nerve injury in dogs using an automatic non-serrated forceps

This study describes a method that not only generates an automatic and standardized crush injury in the skull base, but also provides investigators with the option to choose from a range of varying pressure revels. We designed an automatic, non-serrated forceps that exerts a varying force of 0 to 100 g and lasts for a defined period of 0 to 60 seconds. This device was then used to generate a crush injury to the right oculomotor nerve of dogs with a force of 10 g for 15 seconds, resulting in a deficit in the pupil-light reflex and ptosis. Further testing of our model with Toluidine-blue staining demonstrated that, at 2 weeks post-surgery disordered oculomotor nerve fibers, axonal loss, and a thinner than normal myelin sheath were visible. Electrophysiological examination showed occasional spontaneous potentials. Together, these data verified that the model for oculomotor nerve injury was successful, and that the forceps we designed can be used to establish standard mechanical injury models of peripheral nerves.

Location of the AICA influences the severity but not occurrence of ISSNHL:A reappraisal using high-resolution 3 T MRI

Objective:To investigate the potential influence of anatomical variation in the anterior inferior cerebellar artery(AICA)on the occurrence and severity of idiopathic sudden sensorineural hearing loss(ISSNHL).Methods:Ninety ISSNHL patients were enrolled.The anatomical location of the AICA was exhibited using high-resolution magnetic resonance imaging(MRI),and the various AICA types classified by previously reported Chavda and Gorrie methods were analyzed.The severity of hearing loss in the ipsilateral ear among different AICA types was compared.Results:Approximately 85.6%of subjects had unilateral ISSNHL(uISSNHL),and the others had bilateral ISSNHL(bISSNHL).In the uISSNHL group,the ratios of different AICA types were similar between the ipsilateral and contralateral ears.The ratios of the different AICA types in the bISSNHL group were similar to those in the uISSNHL group.In the uISSNHL group,pure tone audiometry(PTA)thresholds at 2 kHz,4 kHz and 8 kHz of patients with Chavda type II AICA were higher than those of patients with Chavda type I and type III,with a significant difference at 4 kHz between type I and type II.There was a tendency of the PTA threshold in patients with Chavda type II or Gorrie type C to gradually increase from low to high frequency zones.Conclusion:When the AICA enters the IAC(Chavda type II)or crosses between the 7th and 8th cranial nerves(Gorrie type C),the severity and frequency of hearing impairment in ISSNHL but not the occurrence of ISSNHL will be affected.

Intraoperative facial motor evoked potentials monitoring with transcranial electrical stimulation for preservation of facial nerve function in patients with large acoustic neuroma

Background Although various monitoring techniques have been used routinely in the treatment of the lesions in the skull base, iatrogenic facial paresis or paralysis remains a significant clinical problem. The aim of this study was to investigate the effect of intraoperative facial motor evoked potentials monitoring with transcranial electrical stimulation on preservation of facial nerve function. Method From January to November 2005, 19 patients with large acoustic neuroma were treated using intraoperative facial motor evoked potentials monitoring with transcranial electrical stimulation （TCEMEP） for preservation of facial nerve function. The relationship between the decrease of MEP amplitude after tumor removal and the postoperative function of the facial nerve was analyzed. Results MEP amplitude decreased more than 75% in 11 patients, of which 6 presented significant facial paralysis （H-B grade 3）, and 5 had mild facial paralysis （H-B grade 2）. In the other 8 patients, whose MEP amplitude decreased less than 75%, 1 experienced significant facial paralysis, 5 had mild facial paralysis, and 2 were normal. Conclusions Intraoperative TCEMEP can be used to predict postoperative function of the facial nerve. The decreased MEP amplitude above 75 % is an alarm point for possible severe facial paralysis.

Differences in individual susceptibility affect the development of trigeminal neuralgia

Trigeminal neuralgia is a syndrome due to dysfunctional hyperactivity of the trigeminal nerve, and is characterized by a sudden, usually unilateral, recurrent lancinating pain arising from one or more divisions of the nerve. The most accepted pathogenetic mechanism for trigeminal neuralgia is compression of the nerve at its dorsal root entry zone or in its distal course. In this paper, we report four cases with trigeminal neuralgia due to an unknown mechanism after an intracranial intervention The onset of trigeminal neuralgia after surgical interventions that are unrelated to the trigeminal nerve suggests that in patients with greater individual susceptibility, nerve contact with the vascular structure due to postoperative pressure and changes in cerebrospinal fluid flow may cause the onset of pain.