Glomus Tumors

Background

Glomus jugulare tumors are rare, slow-growing, hypervascular tumors that arise within the jugular foramen of the temporal bone. They are included in a group of tumors referred to as paragangliomas, which occur at various sites and include carotid body, glomus vagale, and glomus tympanicum tumors.


Glomus jugulare tumors occur predominantly in women in the fifth and sixth decades of life. Because of the insidious onset of symptoms, these tumors often go unnoticed, and delay in diagnosis is frequent. Because of the location and extent of involvement, glomus jugulare tumors present a significant diagnostic and management, as well as social, challenge.

Lateral view of the initial carotid arteriogram of a 20-year-old woman who presented in June 1970 with episodic hypertension, headaches, and palpitations. Urine catecholamine levels were elevated, and a pheochromocytoma was suspected. She underwent a negative exploratory laparotomy. She subsequently developed palsies of the IX, X, XI, and XII cranial nerves on the right side. A norepinephrine-secreting glomus jugulare tumor with intracranial and cervical extension was identified on radiologic and arteriographic imaging. Arrows delineate the tumor blush. The arrowhead demonstrates branch of the middle meningeal artery providing blood supply to the tumor. This branch was embolized.

History of the Procedure

The glomera jugulare, or glomus bodies, are small collections of paraganglionic tissue. They are derived from embryonic neuroepithelium in close association with the autonomic nervous system and are found in the region of the jugular bulb. In 1840, this tissue was first described by Valentin as ganglia tympanica. In 1878, Krause described the tissue as glandula tympanica. Guild was the first to note the similarity between these collections of tissue and the carotid body. He referred to them as glomus jugulare.

These structures also have been referred to as nonchromaffin paraganglia. The first description of glomus tumor as a hyperplastic glomus bodies was reported by Masson in 1924.


In 1945, Rosenwasser described the first patient diagnosed with glomus jugulare tumor.The patient survived until 1987. An association of glomus tumor with neurofibromatosis Type 1 (NF-1) has been described.
Vascular tumors of the middle ear had previously been reported, but Rosenwasser was the first to recognize the origin of these tumors from the glomus jugulare. He provided the first description of the surgical removal of a glomus jugulare tumor.

Problem

Glomus tumors of the temporal bone occur in the region of the jugular bulb and middle ear. These are rare, vascular, slow-growing tumors, and most are benign. Tumors that originate from the jugular bulb and may extend to involve the middle ear are referred to as glomus jugulare tumors.
Glomus tumors are also referred to as chemodectomas or nonchromaffin paragangliomas.

Paragangliomas are often found at other sites, including the middle ear (glomus tympanicum tumor), the carotid body (carotid body tumor), and the vagus nerve in proximity to the inferior (nodosum) vagal ganglion (glomus vagale tumor, glomus intravagale tumor). Affected sites that are much less commonly reported are the periaortic area, trachea, larynx, mandible, nose, ciliary ganglion, and fallopian canal. Optimal treatment of temporal bone glomus tumors remains controversial.

Epidemiology

Frequency

Glomus tumors occur with an estimated annual incidence of 1 case per 1.3 million people.Although rare, glomus tumors are the most common tumor of the middle ear and are second to vestibular schwannoma as the most common tumor of the temporal bone.

The female-to-male ratio is 3-6:1. Glomus jugulare tumors have also been noted to be more common on the left side, especially in females.
Most tumors occur in patients aged 40-70 years, but cases have been reported in patients as young as 6 months and as old as 88 years. Multicentric tumors are found in 3-10% of sporadic cases and in 25-50% of familial cases.

Etiology

Glomus jugulare tumors originate from the chief cells of the paraganglia, or glomus bodies, located within the wall (adventitia) of the jugular bulb, and can be associated with either the auricular branch of the vagus nerve (Arnold nerve) or the tympanic branch of the glossopharyngeal nerve (Jacobson nerve). Paraganglia are small (< 1.5 mm) masses of tissue composed of clusters of epithelioid (chief) cells within a network of capillary and precapillary caliber vessels. The number seems to increase until the fourth decade of life and then seems to decline. Paraganglia develop from the neural crest and are believed to function as chemoreceptors. Based on the presence of catecholamines and neuropeptides, paraganglia are included in the amine precursor uptake and decarboxylase (APUD) system, which has more recently been referred to as the diffuse neuroendocrine system (DNES).

Although most paragangliomas are sporadic, they can be familial with autosomal dominant inheritance and incomplete penetrance. The development of tumors in familial cases is dependent on age and on the sex of the affected parent. The nonchromaffin paragangliomas have a familial tendency. Tumors rarely occur in people younger than 18 years, and as a result of suspected genomic imprinting, only children of males possessing the disease gene develop tumors. The gene responsible for hereditary paragangliomas has been localized to band 11q23.

Pathophysiology

Glomus tumors are encapsulated, slowly growing, highly vascular, and locally invasive tumors. Sen et al described histological structure of glomus tumors as a dense matrix of connective tissue among nerve fascicles.These tumors tend to expand within the temporal bone via the pathways of least resistance, such as air cells, vascular lumens, skull base foramina, and the eustachian tube. They also invade and erode bone in a lobular fashion, but they often spare the ossicular chain.

Initially, the skull base erodes in the region of the jugular fossa and posteroinferior petrous bone, with subsequent extension to the mastoid and adjacent occipital bone (see the image below). Significant intracranial and extracranial extension may occur, as well as extension within the sigmoid and inferior petrosal sinuses. Neural infiltration is also common.

Lateral carotid arteriogram obtained 22 years after radiation therapy in a 20-year-old woman who presented in June 1970 with episodic hypertension, headaches, and palpitations.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

The parenchyma of the paraganglia consists of 2 primary cell types. Type I cells are more common and are typically round with indistinct cell borders. Type II cells are smaller and irregularly shaped.
Metastases from glomus tumors occur in approximately 4% of cases.A reduction in the proportion of type II cells and a poorer staining of type I cells for s-100 and glial fibrillary acidic protein are reported to be correlated with an increased tumor grade. A metastatic lesion is distinguished from a multicentric lesion based on location. Metastases have been found in the lung, lymph nodes, liver, vertebrae, ribs, and spleen. Malignancy of the tumor probably is related to p53 and p16INK4A mutations.

Additional studies using immunohistochemical techniques revealed that malignant glomus tumors are characterized by the presence of MIB-1, p53, Bcl-2 and CD34.Up to 4% of the tumors are functional and produce clinically significant levels of catecholamines, norepinephrine, or dopamine with symptoms mimicking a pheochromocytoma. Pheochromocytoma, parathyroid adenoma, and thyroid carcinoma have been reported in association with glomus jugulare tumors.

The Glasscock-Jackson and Fisch classifications of glomus tumors are widely used. The Fisch classification of glomus tumors is based on extension of the tumor to surrounding anatomic structures and is closely related to mortality and morbidity.

• Type A tumor - Tumor limited to the middle ear cleft (glomus tympanicum)
• Type B tumor - Tumor limited to the tympanomastoid area with no infralabyrinthine compartment involvement
• Type C tumor - Tumor involving the infralabyrinthine compartment of the temporal bone and extending into the petrous apex
• Type C1 tumor - Tumor with limited involvement of the vertical portion of the carotid canal
• Type C2 tumor - Tumor invading the vertical portion of the carotid canal
• Type C3 tumor - Tumor invasion of the horizontal portion of the carotid canal
• Type D1 tumor - Tumor with an intracranial extension less than 2 cm in diameter
• Type D2 tumor - Tumor with an intracranial extension greater than 2 cm in diameter

Presentation

The clinical course of temporal bone glomus tumors reflects their slow growth and paucity of symptoms. Often, a significant delay in diagnosis occurs, and tumors may be large when first identified.

The most common symptoms are conductive hearing loss and pulsatile tinnitus. Other aural signs and symptoms are ear fullness, otorrhea, hemorrhage, bruit, and the presence of a middle ear mass. Significant ear pain is uncommon. Involvement of the inner ear produces vertigo and sensorineural hearing loss.

Cranial nerve involvement produces hoarseness and dysphagia. The presence of jugular foramen syndrome (paresis of cranial nerves IX-XI) is pathognomonic for this tumor, but it usually follows one year after the initial symptoms of hearing loss and pulsatile tinnitus. Less commonly, glomus tumors produce facial nerve palsy, hypoglossal nerve palsy, or Horner syndrome.
Headache, hydrocephalus, and elevated intracranial pressure may be produced by intracranial extension of the tumor. Ataxia and brainstem symptoms may also develop. Involvement of the dural sinuses may mimic sinus thrombosis.

In about 2-4% of cases, the first or leading symptoms are hypertension and tachycardia (pheochromocytomalike symptoms) produced by catecholamines, norepinephrine, or dopamine excreted by the tumor. Also, somatostatin, vasoactive intestinal polypeptide (VIP), calcitonin, and neuron-specific enolase may be produced by the tumor. Other related symptoms include headache, perspiration, pallor, and nausea.

Otoscopic examination reveals a characteristic, pulsatile, reddish-blue tumor behind the tympanic membrane that is often the beginning of more extensive findings (ie, the tip of the iceberg).
Audiologic examination reveals mixed conductive and sensorineural hearing loss. The sensorineural component tends to be more significant with larger tumors.

Plain skull radiography may show enlargement of the lateral jugular foramen and fossa. Axial and coronal computed tomography (CT) scanning with thin sections are superior at demonstrating the extent of bone destruction. Magnetic resonance imaging (MRI) with gadolinium-diethylenetriamine pentaacetic acid (DTPA) contrast is best for delineating tumor limits. Glomus tumors on T1- and T2-weighted MRI have characteristic soft tissue mixed intensity with intermixed high-intensity signals and signal voids (ie, salt and pepper appearance) representing fast flowing blood. A combination of CT scanning and contrast MRI is the imaging regimen of choice for glomus jugulare tumors.

Unless carotid arteriography is necessary for preoperative evaluation and/or embolization, noninvasive techniques are preferred; however, for large tumors involving the internal carotid artery (ICA), preoperative carotid arteriography with cross-compression or trial balloon occlusion is recommended. The venous drainage systems also need to be carefully studied before sinus occlusion is carried out during surgical resection.

For tumors with large intracranial extension, vertebral arteriography is advised to exclude arterial feeders from the posterior circulation.

Differential diagnoses include the following:

• Chordoma
• Otitis Media
• Eosinophilic Granuloma (Histiocytosis X)
• Meningioma
• Schwannoma
• Neurofibroma
• Chondrosarcoma
• Carcinoma (primary and metastatic)
• Cholesteatoma
• Osteoma
• Otosclerosis
• Chronic mastoiditis
• Cholesterol granuloma
• Aneurysm
• Aberrant intrapetrous internal carotid artery
• Idiopathic hemotympanum
• Arterious malformation
• Prominent jugular bulb
• Persistent stapedial artery
• Lymphoma

Indications

See Surgical therapy for specific surgical indications.

Relevant Anatomy

Most jugulotympanic paraganglia are located in the adventitia of the jugular bulb within the jugular foramen. 

The main blood supply is via the ascending pharyngeal artery from the external carotid artery (ECA) and branches from the petrous portion of the internal carotid artery (ICA). Larger glomus jugulare tumors may also have blood supply from other branches of the ECA, ICA, vertebral artery, and thyrocervical trunk.

The walls of the jugular foramen are formed anterolaterally by the petrous bone and posteromedially by the occipital bone. The canal follows an anterior, inferior, and lateral direction to exit the skull.

The posterolateral portion of the foramen (pars venosa) contains the jugular bulb, posterior meningeal artery, and cranial nerves X and XI. The anteromedial portion (pars nervosa) contains the inferior petrosal sinus and cranial nerve IX. The jugular bulb is situated between the sigmoid sinus and the internal jugular vein. The lower cranial nerves are situated medial to the medial wall of the jugular bulb. The inferior petrosal sinus enters the medial aspect of the jugular bulb via several channels anterior to cranial nerves IX, X, and XI.

Many important structures are in proximity to the jugular bulb, including the internal auditory canal, the posterior semicircular canal, the middle ear, the medial external auditory canal, the facial nerve (posterolaterally), and the ICA (anteriorly) within the carotid canal. At the extracranial end of the jugular foramen, the ICA, internal jugular vein, and cranial nerves VII, X, XI, and XII are within a 2-cm area.

Contraindications

 Because this tumor is rare and may present with various symptoms, surgery may be contraindicated for various reasons, including age and general physical condition. Surgical resection of the glomus tumor is relatively simple and complication free for type I tumors. Large tumors that affect the lower cranial nerves and extend beyond the petrous apex carry a significant risk of postoperative complications, especially in older patients. In these cases, other modalities of treatment should be considered (eg, embolization, radiation, gamma knife radiosurgery, intratumoral injection of cyanoacrylate glue).

Glomus Tumors Workup

Staging

The Glasscock-Jackson and Fisch classifications of glomus tumors are widely used. The Fisch classification of glomus tumors is based on extension of the tumor to surrounding anatomic structures and is closely related to mortality and morbidity.

• Type A tumor - Tumor limited to the middle ear cleft (glomus tympanicum)
• Type B tumor - Tumor limited to the tympanomastoid area with no infralabyrinthine compartment involvement
• Type C tumor - Tumor involving the infralabyrinthine compartment of the temporal bone and extending into the petrous apex
• Type C1 tumor - Tumor with limited involvement of the vertical portion of the carotid canal
• Type C2 tumor - Tumor invading the vertical portion of the carotid canal
• Type C3 tumor - Tumor invasion of the horizontal portion of the carotid canal
• Type D1 tumor - Tumor with an intracranial extension less than 2 cm in diameter
• Type D2 tumor - Tumor with an intracranial extension greater than 2 cm in diameter
   
   

  Glomus Tumors Treatment & Management

  Medical Therapy

  Some cases require no treatment. Often, glomus jugulare tumors are diagnosed within the sixth or seventh decade of life and can be followed by imaging only and may not need surgical intervention.
  
  A study from Vanderbilt University found that in the absence of brainstem compression or concern for malignancy, observation of  glomus jugulare tumors can be a viable initial management approach for elderly patients. Of 15 patients studied (80% female; median age, 69.6 yr), radiologic growth occurred in 5 patients. The median growth rate of the 5 enlarging tumors was 0.8 mm/yr (range, 0.6-1.6 mm/yr) using maximum linear dimension, or 0.4 cm³/yr (0.1-0.9 cm³/yr) with volumetric analysis. No deaths were attributable to tumor progression or treatment. 
  
  Medical therapy may be indicated in some cases. Alpha-blockers and beta-blockers are useful for tumors secreting catecholamines. They are usually administered for 2-3 weeks before embolization and/or surgery to avoid potentially lethal blood pressure lability and arrhythmias. Successful treatment of pulmonary metastases with etoposide (VP-16) and cisplatin has been described. In a preliminary report, a somatostatin analogue (octreotide) has been successfully used for growth control of somatostatin receptor–positive tumors.
  

  Surgical Therapy

  Surgery is the treatment of choice for glomus jugulare tumors. However, more recently, radiation therapy, particularly a gamma knife radiosurgery, has been shown to provide good tumor growth control with a low risk of treatment-related cranial nerve injury.
  
  
  A large retrospective, multicenter, international study analyzed the long-term outcome in 132 patients with primary radiation treatment or radiation after partial resection of a glomus tumor. The study found long-term successful control of the tumor growth, improvement of tinnitus and overall neurological status, as well as cranial nerve function. These results strongly suggest that gamma knife radiosurgery is becoming the treatment of choice for glomus tumors. 
  
  A German study of 32 patients who underwent stereotactic radiosurgery for glomus jugulare tumors showed that stereotactic linear accelerator (LINAC) radiosurgery achieved excellent long-term tumor control, along with a low rate of morbidity. According to the study, following LINAC stereotactic radiosurgery, 10 of 27 patients showed a significant improvement of their previous neurologic complaints, whereas 12 patients remained unchanged. No tumor progression was observed. Five patients died due to unrelated causes. Overall survival rates after 5, 10, and 20 years were 100%, 95.2% and 79.4%, respectively.
  
  
  Because resection of glomus jugulare tumors can be challenging due to their inherent vascularity, preoperative embolization of these tumors with ethylene vinyl alcohol (Onyx) has been proposed.A study by Gaynor et al showed a dramatic reduction of blood loss and facilitation of surgical resection, but these results came at the price of a higher incidence of cranial nerve neuropathy.
  
  
  The surgical approach depends on the localization and extension of the tumor. Intraoperative monitoring including EEGs and somatosensory-evoked potentials (SSEPs) are routinely used.
  Fisch type A tumors (see Pathophysiology) can be excised by a transmeatal or perimeatal approach.
  
  Type B tumors (see Pathophysiology) require an extended posterior tympanotomy.
  Type C tumors (see Pathophysiology) require radical resection via a standard combined transmastoid-infratemporal or transtemporal-infratemporal approach with or without internal carotid artery (ICA) trapping, preceded by external carotid artery (ECA) embolization or superselective embolization. Intraoperatively, temporarily occlude the transverse or sigmoid sinus with EEG monitoring to determine whether vein bypass should be performed for total resection. Surgery leads to therapeutic success in about 90% of patients. Intratumoral injection of cyanoacrylate glue has been proposed to control bleeding.
  
  Large type D tumors (see Pathophysiology) need to be treated with a combined otologic and neurosurgical approach. An infratemporal approach with a skull base resection and a posterior fossa exploration are the most advisable in attempting to remove the entire tumor. Partial resection of the tumor needs to be followed by radiation and follow-up MRI/CT scanning.
  
  Radiation therapy and radiosurgery may be indicated. Both classic fractionated radiation therapy (40-50 Gy) and stereotactic radiosurgery (eg, gamma knife surgery) are successful in long-term control of tumor growth and in decrease of catecholamine excretion in functional tumors; however, the short duration of observation after stereotactic radiosurgery does not allow for definite conclusions. Radiation treatment is advised as the sole treatment modality for elderly or infirm patients who are symptomatic, especially those with extensive or growing tumors.
  
  Gross total resection of some extensive tumors may be extremely difficult and may carry unwarranted risk. In such cases, radiotherapy may be indicated to treat residual tumor following subtotal resection.However, a 2004 study by Prahbu showed that even complex glomus tumors can be managed surgically. See the images below.
  
  

  

  A significant decrease of tumor vascular blush (arrows) following embolization of a norepinephrine-secreting glomus jugulare tumor with intracranial and cervical extension.

  
  

  

  CT imaging demonstrates the extent of bony destruction (white and black arrows) by the tumor. The normal jugular foramen on the left (arrow head) is shown for comparison. The patient subsequently underwent surgical resection of the extracranial portion of this extensive tumor. The remaining intracranial portion was treated with radiation therapy (54 Gy). Follow-up evaluations, including imaging and laboratory investigations, demonstrated long-term control of both tumor growth and catecholamine production.

  
  

  Preoperative Details

  If routine screening for catecholamine is positive (3 times the reference range), alpha-blockers and beta-blockers are administered for 2-3 weeks before surgery and embolization. This helps to avoid blood pressure lability and arrhythmias. In emergent cases, 3 days of treatment is adequate.
  

  Intraoperative Details

  Surgical approach depends on the localization and extent of the tumor (see Pathophysiology). Fisch type A tumors can be excised by a transmeatal or perimeatal approach. Type B tumors require an extended posterior tympanotomy. Type C tumors require radical resection via a standard combined transmastoid-infratemporal or transtemporal-infratemporal approach with or without ICA trapping, preceded by external carotid artery embolization or superselective embolization. Surgery leads to therapeutic success in about 90% of patients. Treat large type D tumors with a combined otologic and neurosurgical approach. An infratemporal approach with a skull base resection and a posterior fossa exploration are advisable in the attempt to remove the entire tumor.
  

  Postoperative Details

  Patients are usually in the sixth decade of life; therefore, careful monitoring of cardiac function is advisable, especially if a catecholamine secreting tumor was only partially resected.
  Postoperative lower cranial nerve deficits need to be carefully diagnosed, and, when present, early rehabilitation is advocated.
  

  Follow-up

  Radiologic and, when indicated, endocrinologic monitoring for tumor growth or regrowth is indicated every 6 months to 1 year for 2 years and then, depending on the dynamics of the tumor behavior, every 2 years. See the images below.
  

  

  Lateral carotid arteriogram obtained 22 years after radiation therapy in a 20-year-old woman who presented in June 1970 with episodic hypertension, headaches, and palpitations.

  
  

  

  Corresponding MRI of the tumor depicted in the previous image indicating no evidence of tumor growth over time.

  
  

  Complications

  Complications of surgery include death, cranial nerve palsies, bleeding, cerebrospinal fluid (CSF) leak, meningitis, uncontrollable hypotension/hypertension, and tumor regrowth.
  Complications of radiation include ICA thrombosis, secondary tumor development, pituitary-hypothalamic insufficiency, CSF leak, tumor growth, and radiation necrosis of bone, brain, or dura.
  

  Outcome and Prognosis

  Glomus jugulare tumors may grow slowly and produce cranial nerve palsies that, to a certain point, are benign and mostly cosmetic. However, despite this optimistic assessment, a recent study showed a long-term reduced quality of life in patients with glomus tumors.
  
  The mortality rate is 6.2% among patients treated with radiation and 2.5% among those treated surgically. The overall mortality rate is 8.7%.
  Twenty years after treatment, the survival rate is 94%, and 77% of patients remain symptom free. In 1945, Rosenwasser described the first patient diagnosed with glomus jugulare tumor. The patient survived until 1987.
  

  Future and Controversies

  Surgery is the treatment of choice for glomus tumors, and its effectiveness will improve with intraoperative guiding and imaging systems.
  
  The cooperative work of neurosurgeons and neuro-otologists to surgically resect Fisch type A, B, and C tumors has proven to be of value. However, definitive optimal treatment of type D glomus jugulare tumor is still controversial.
  
  Because of its long-term effects on the bone and brain, radiation that is not stereotactically targeted is outdated. Radiosurgery with its influence on neuro-oncology must be proven useful in treatment of these slowly growing tumors. 
  
  Continued tumor growth and postsurgical damage to the lower cranial nerves are issues that still need to be successfully addressed.
  Recent genetic research on familial glomus jugulare tumors suggests future directions of treatment towards gene manipulation.
  

   

   
   
   

 

Causes and Treatments of Migraine and Related Headaches

Migraine Headaches Introduction

Headaches are very common; in fact, almost everyone will have a headache at some point. Headaches have been written about since the time of the Babylonians. Migraine headaches are even discussed in the Bible. Some very famous historical figures (for example, Napoleon Bonaparte) suffered from severe headaches.
Experts do not agree about what causes headaches, but they agree that more studies are needed. Headaches are hard to study because of the following reasons:

• People experience pain differently (in other words, a headache one person rates as a 10 on a scale of 10 might be rated as a 5 by another person).
• Measuring headache pain in a standard way that accounts for the personal way people feel pain is almost impossible.
• Studies are limited to human subjects.

Although headaches might rarely be due to infections or diseases, most are probably the result of an inborn protective mechanism responding to an external environmental stress. Headaches can be divided into 2 broad categories: primary headaches and secondary headaches. Primary headaches are not caused by problems with a person's internal structure or organs or by bacteria, viruses, or other organisms. Migraine, cluster, tension, and rebound headaches are types of primary headache. Secondary headaches are those caused by an underlying structural or organic disease.
Several observations support this idea. When exposed to very high or low temperatures, people sometimes develop a migrainelike headache. (Migraine headaches are sometimes called vascular headaches. Vascular means having to do with the blood vessels.) These headaches can also suddenly arise in some people when they do not get enough sleep or food.
Common triggers of migraine headaches include heat, stress, and lack of sleep or food. Not every headache sufferer is sensitive to these triggers, but virtually all persons with migraine headaches (called migraineurs) have some environmental trigger. About 70% of migraineurs have a first-degree relative (parent, brother, sister, or child) with a history of migraine. People with an inherited tendency for headaches may respond more easily than others to these external stress factors. Some experts have therefore thought that headache is an adaptive and developed response. Most primary headaches slowly develop over minutes to hours. The pain experienced in headache is transmitted by the slowest of all unmyelinated nerves. Unmyelinated nerves lack a myelin sheath, or covering, and send impulses slowly.

Migraine Headaches

Migraine headaches affect 17% of females and 6% of males in the United States. Before puberty, boys and girls get migraines at about the same rate, although boys may get them slightly more often. In individuals older than 12 years, the frequency of migraines increases in both males and females. The frequency declines in individuals older than 40 years.
In the United States, white women have the highest frequency of migraine, while Asian women have the lowest. The female-to-male ratio increases from 2.5:1 at puberty to 3.5:1 at age 40 years, after which it declines. The rate of migraine headaches in females of reproductive age has increased over the last 20 years.
Migraine Headaches, Causes
The causes of migraine headaches are not clearly understood. In the 1940s, it was proposed that a migraine begins with a spasm, or partial closing, of the arteries leading to the main part of the brain (called the cerebrum). The first spasm decreases blood supply to part of the brain, which causes the aura (lights, haze, zig-zag lines, or other symptoms) that some people experience. These same arteries then become too relaxed, which increases blood flow and causes pain.
About 30 years later, the chemicals dopamine and serotonin were found to play a role in migraine headaches. (These chemicals are called neurotransmitters.) Dopamine and serotonin are normally found in the brain, but they can cause blood vessels to act in uncharacteristic ways if they are present in abnormal amounts or if the blood vessels are unusually sensitive to them.
Together, these 2 theories have come to be known as the neurovascular theory of migraine, and it is presently believed that both theories provide insight into the causes of headache.
Various triggers are thought to initiate migraine headaches in people who are prone to developing them. Different people may have different triggers.

• Smoking has been identified as a trigger for many people.
  
  
• Certain foods, especially chocolate, cheese, nuts, alcohol, and monosodium glutamate (MSG), may trigger migraine headaches. (MSG is a flavor enhancer used in many foods, including Chinese dishes.)
  
  
• Missing a meal or changing sleep patterns may bring on a headache.
  
  
• Stress and tension are also risk factors. People often have migraines during times of increased emotional or physical stress.
  
  
• Contraceptives (birth control pills) are a common trigger. Women may have migraines at the end of the pill cycle as the estrogen component of the pill is stopped. This is called an estrogen-withdrawal headache.

Migraine Headaches, Association with other diseases Migraines may occur more frequently in persons with the following diseases:

• Epilepsy
  
  
• Familial dyslipoproteinemias (abnormal cholesterol levels)
  
  
• Hereditary hemorrhagic telangiectasia
  
  
• Tourette syndrome
  
  
• Hereditary essential tremor
  
  
• Hereditary cerebral amyloid angiopathy
  
  
• Ischemic stroke: Migraine with aura is a risk factor (odds ratio, 6:1).
  
  
• Depression and anxiety
  
  

Migraine Headaches, Clinical features Headache is seldom the only feature of migraine, and it is sometimes entirely absent. Some patients report a prodromal phase (an early phase before the start of a full-blown condition, usually accompanied by certain symptoms) 24 hours before the headache. Symptoms during this early phase may include irritability, depression, or hyperexcitability. Migraine with aura (classic migraine) usually has several early visual symptoms, including photopsia (flashes of light) and fortification spectra (wavy linear patterns in the visual fields), or migrating scotoma (patches of blurred or absent vision). The headache is usually described as throbbing or pulsing. Migraines are typically unilateral (affecting one side), but the side affected in each episode may change. Unilaterality is not a requirement for migraine diagnosis, however.
Nausea, vomiting, photophobia (sensitivity to light), phonophobia (sensitivity to sound), irritability, and malaise (general discomfort or uneasiness, an “out-of-sorts” feeling) are common. The headache usually lasts for 6-24 hours. Migraineurs generally prefer to lie quietly in a dark room.
Sometimes, a history of certain triggers can be identified. Common associations in migraine include head injury, physical exertion, fatigue, drugs (nitroglycerine [Nitrostat], histamine, reserpine [Serpasil], hydralazine [Apresoline], ranitidine [Zantac], estrogen), and stress.
If the headache is always on one side, the doctor must look for a structural lesion by using imaging studies like magnetic resonance imaging (MRI). Having a history of migraine attacks and determining what brings them on are important, because a secondary headache can mimic a migraine headache and thus mask a new medical problem.
Migraine Headaches, Variants

• Migraine without aura (common migraine) is a throbbing headache without the early visual symptoms.
  
  
• Ophthalmic migraine is a type of migraine associated with eye problems. This variant is sometimes called retinal migraine or ocular migraine.
  
  
• Abdominal migraine is the term used to describe periodic abdominal pain in children that is not accompanied by headache.
  
  
• Complicated migraine is a type of migraine in which migraine attacks are accompanied by permanent problems like paralysis.
  
  
• Vertebrobasilar migraine manifests without headaches but with symptoms like vertigo, dizziness, confusion, speech disturbances, tingling of extremities, and clumsiness.
  
  
• Status migrainosus is the term used to describe migraine attacks that persist for days. These attacks may result in complications such as dehydration.
  
  

Migraine Headaches, Treatment overview

• Avoid factors that cause a migraine attack (for example, lack of sleep, fatigue, stress, certain foods, vasodilators).
  
  
• Treat accompanying conditions (for example, anxiety, depression).
  
  
• Oral birth control agents (contraceptives) may increase the frequency of headaches in females. Women may be advised to discontinue oral contraceptives (or to use a different form) for a trial period to see if they are a factor.
  
  

Migraine Headaches, Abortive treatment Abortive treatments stop migraines quickly. Many drugs are now available for immediate treatment of migraine attacks. The goal is rapid and effective relief of headache. The most effective drugs for stopping a migraine are the triptans, which specifically target serotonin receptors. They are all very similar in chemical structure and action. The following is a list of triptans:

• Sumatriptan (Imitrex, Imigran)
  
  
• Zolmitriptan (Zomig, Zomig-ZMT)
  
  
• Naratriptan (Amerge, Naramig)
  
  
• Rizatriptan (Maxalt, Maxalt-MLT)
  
  
• Almotriptan (Axert)
  
  
• Frovatriptan (Frova)
  
  
• Eletriptan (Relpax)
  
  

The following nontriptans also act on the serotonin receptors. They also act on some other receptors, most likely on those for dopamine and noradrenalin. Sometimes, they are effective when the triptans fail.

• Ergotamine tartrate (Cafergot)
  
  
• Dihydroergotamine (D.H.E. 45 Injection, Migranal Nasal Spray)
  
  
• Acetaminophen-isometheptene-dichloralphenazone (Midrin)
  
  

The following are primarily used when nausea is a complicating factor in migraine headache. In some cases, they also help relieve the headache.

• Prochlorperazine (Compazine)
  
  
• Promethazine (Phenergan)
  
  

Combination drugs like butalbital-acetaminophen-caffeine (Fioricet), butalbital-aspirin-caffeine (Fiorinal), or acetaminophen with codeine (Tylenol With Codeine) are general painkillers in the narcotic class. They can help relieve any kind of pain to some degree, whereas the triptans, ergotamines, and Midrin are used specifically for headaches and do not help relieve arthritis, back pain, or menstrual cramps.
Treatment strategies are more successful if they are tailored to the individual patient and are initiated early in the headache.
Patients with severe nausea and vomiting at the onset of an attack may at first respond best to intravenous prochlorperazine. These patients may be dehydrated; adequate fluid intake is necessary.
Vasoconstrictors (agents that narrow the blood vessels), such as ergotamines or triptans, should not be given to patients with known complicated migraine without the advice of a headache specialist. Instead, acute attacks should be treated with one of the other available agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs) or prochlorperazine.
Mild and infrequent attacks may not always require the use of ergotamines or triptans and may be adequately treated with acetaminophen (Tylenol), NSAIDs, propoxyphene (Darvon, Darvocet), or a combination of these.
About 40% of all attacks do not respond to triptans or any other substance. If all else fails, migraineurs with an attack lasting more than 72 hours (status migrainous) can be treated with intravenous medications. Brief hospitalization may be needed.
Migraine Headaches, Preventive treatment
Patients who have frequent acute migraine attacks and report that the attacks affect their quality of life should consider preventive therapy as a supplement to the specific headache-stopping drugs (abortive treatments) they use.
The goals of preventive therapy include decreasing the frequency and severity of acute attacks and improving quality of life.
Patients with complicated migraine headaches who have a history of neurological symptoms associated with their attacks are definite candidates for preventive therapy. For these patients, even a single previous complicated migraine episode qualifies them for long-term preventive therapy.
The choice of preventive medication should be tailored to the individual's profile, taking into account comorbidities (concurrent medical conditions) such as depression, weight gain issues, exercise tolerance, asthma, and pregnancy plans. All medications have side effects; therefore, selection must be individualized.
Preventive drugs include beta-blockers, tricyclic antidepressants, some anticonvulsants, calcium channel blockers, cyproheptadine (Periactin), and NSAIDs such as naproxen (Naprosyn). Unlike the specific headache-stopping drugs (abortive drugs), most of these were developed for other conditions and have been coincidentally found to have headache preventive effects. The following drugs also have preventive effects; unfortunately, they also have more side effects:

• Methysergide maleate (Sansert): This drug has many side effects.
  
  
• Lithium (Eskalith, Lithobid): This drug has many side effects.
  
  
• Indomethacin (Indocin): This drug can cause psychosis in some people with cluster headaches.
  
  
• Steroids: Prednisone (Deltasone, Meticorten) works extremely well for some people and should be tried if other therapies fail.
  
  

How long a person should follow a preventive therapy plan is a function of his or her response to the drug being taken. If headaches completely stop, it is reasonable to gradually reduce the dosage so long as headaches do not recur.

Cluster Headaches

Cluster headaches have been called histamine cephalalgia, Horton neuralgia, and erythromelalgia. The causes of cluster headaches are not known with certainty. The mechanisms by which the body produces cluster headache pain and other symptoms are also not known for sure.
Cluster Headaches, Prevalence
Cluster headaches are rare. (Less than 1% of the population experience them.) People who do have such headaches usually start to have them when aged 20-40 years. Males get them more often than females (by a ratio of 5-8:1). Usually, no family history of cluster headaches is noted.
Cluster Headaches, Clinical features
Typically, cluster headaches come on with no warning. The signs and symptoms may include intense burning or penetrating pain, often described as a stabbing or hot poker sensation, in or around one eye or temple, occasionally spreading to the forehead, nose, cheek, or upper gum and jaw.
Cluster headaches usually occur on one side of the head. Pain is often penetrating and lasts from 15 minutes to 4 hours. Cluster headaches often cause people to awaken in the middle of the night. During a cluster headache, people are restless and may find relief in pacing or crying. Cluster headaches start rapidly over a few minutes. Periodicity (occurring at regular intervals) is characteristic of cluster headaches. Clusters of headaches are experienced, each cluster lasting as long as several months, once or twice a year. Using alcohol, histamines, or nitroglycerine during a cluster headache may worsen the attack.
Certain personality and physical characteristics have been associated with cluster headaches. A leonine (lionlike) appearance is one of them. Strong associations with smoking, alcohol use, and previous head and face trauma have been noted.
Cluster Headaches, Abortive treatment

Most of the headache-stopping drugs (abortive drugs) effective in treating migraine headaches are also effective in stopping cluster headaches, suggesting that the two types are related.

• Oxygen therapy: This is the treatment of choice and is very safe and effective. Early in an attack, oxygen delivered through a face mask has been known to either stop an attack or diminish its intensity. Why this works is unknown.
  
  
• Occipital nerve steroid injection (methylprednisolone acetate [Depo-Medrol]): An injection of this drug may stop a cluster headache attack.

Cluster Headaches, Preventive therapy
As with the abortive drugs, most of the preventive drugs effective in treating migraine headaches are also effective in preventing cluster headaches, again suggesting that the two types are related.

Daily Chronic Headache

Daily chronic headache is defined as a headache that is present for more than 15 days a month and for at least 6 months a year. Three main types are noted: chronic tension-type headache, migraine chronic tension-type headache complex, and rebound (analgesic abuse) headache. How the body produces chronic daily headaches is not well understood. They have been associated with depression, anxiety, bipolar disorders, panic attacks, mouth/jaw problems, stress, and drug overuse.

Chronic tension-type headache

Chronic tension-type headaches are not associated with a history of migraine or cluster headaches. Patients report almost constant daily headaches of mild-to-moderate intensity. The headache is described as a feeling of tightness or pressure that is not worsened, and may actually be improved, by activity. Patients with chronic tension-type headaches can carry on their daily activities. Nausea and photophobia (sensitivity to light) may occur, but vomiting usually does not. A small group of patients may have head and neck tenderness.
Chronic tension-type headache, Treatment
Patients who are less responsive to previous treatment and those with conditions like depression and stress may be good candidates for psychological treatments. Biofeedback has been successful in patients with tension headache. They are taught how to relax their tense muscles. Thermal biofeedback, in which patients are taught to increase their body temperatures to improve their headaches, has also worked. Other less conventional treatments, such as relaxation training and stress-coping training, may be helpful in the long term.

Transformed migraine

Migraine transformation has been a term used by some experts to describe when intermittent migraines become daily migraines. This type of headache is believed to be associated with analgesic or ergotamine overuse. Patients report intermittent typical migraine attacks along with the daily chronic headaches.
Transformed migraine, Treatment

• Detoxification
  
  
  • Stopping all analgesics and headache-related medications is best done in an inpatient setting.
    
    
  • Doctors may prescribe a clonidine (Catapres) patch to lessen withdrawal symptoms if narcotic analgesics are involved.
  
  
• Preventive: Preventive treatments for transformed migraine headaches are identical to those used for the other types of migraine headache.
  
  

Other uncommon chronic headaches
Hemicrania continua and chronic paroxysmal hemicrania are uncommon forms of chronic headache. Chronic paroxysmal hemicrania is a severe chronic headache similar to cluster headache. It has a male predominance. The headaches are paroxysmal (pulsing), with pain in the temple/eye region lasting 20-30 minutes. The paroxysms occur several times a day. This type of headache can last several years. Treatment with indomethacin (Indocin) results in a dramatic response.

Secondary Headaches

Secondary headaches are related to physical problems and include the following:

• Space-occupying intracranial (inside the head) lesions: The headaches associated with intracranial tumors are initially paroxysmal. Classic headaches of this type wake a person from sleep at night and are associated with projectile vomiting. With time, the headaches may become continuous and intensify with activities that increase intracranial pressure (for example, coughing, sneezing).
• 
  
• Meningeal irritation: Meningitis, especially the chronic forms (tuberculous, fungal), can irritate the meninges (membrane covering the brain and spinal cord) and result in chronic headaches. The headaches are often diffuse (spread out).  
• 
  
• Posttraumatic headache: Headache can be part of a postconcussion syndrome. Patients may report vague headaches, fatigue, memory problems, and irritability for months or years after the traumatic event.
• 
  
• Temporal arteritis: This is an inflammation of some of the arteries of the extracranial (outside the skull) arteries. The headache is generally localized to the affected side and may be worsened by chewing.
• 
  
• Post-lumbar puncture (spinal tap) headache: Lumbar puncture can cause a headache that is worsened by sitting up from a lying position. It usually goes away by itself after the person drinks fluids and has caffeine in some form.
• 
  
• Referred pain: Headache may be a form of referred pain from neighboring structures. Dental disease can cause chronic headaches. Upper neck diseases or arthritis can also cause headaches. People with acute sinus or jaw problems can experience headaches; however, uncomplicated chronic sinusitis does not cause headaches.
• 
  
• Idiopathic intracranial hypertension (benign intracranial hypertension, pseudotumor cerebri): This disorder, most common in young women, is due to increased intracranial (within the head) pressure in the absence of any structural central nervous system abnormality or obstruction to the flow of cerebrospinal fluid.

Synonyms and Keywords

headache, headaches, headache medicine, headache medicines, daily headache, causes and treatments of migraine and related headaches, treatment for migraines, treatment of migraines, primary headache, secondary headache, migraine headache, migraine headaches, status migrainous, migraineur, cluster headache, cluster headaches, histamine cephalalgia, Horton neuralgia, erythromelalgia, chronic daily headache, hemicrania continua, chronic paroxysmal hemicrania, tension headache, tension headaches, tension-type headache, rebound headache, vascular headache, ophthalmoplegic migraine, aspirin abuse, analgesic abuse, estrogen-withdrawal headache

Neurosurgery for Cerebral Aneurysm

Overview

The word aneurysm comes from the Latin word aneurysma, which means dilatation. Aneurysm is an abnormal local dilatation in the wall of a blood vessel, usually an artery, due to a defect, disease, or injury.
Aneurysms can be true or false. A false aneurysm is a cavity lined by blood clot. The 3 major types of true intracranial aneurysms are saccular, fusiform, and dissecting. See image below.

Common locations of cerebral saccular aneurysms. The relative incidences are shown

This article reviews the types, pathology, clinical picture, and management of intracranial aneurysms. For patient education resources, see the Headache Center, as well as Aneurysm, Brain. 

Causes and Classification of Intracranial Aneurysms

The common causes of intracranial aneurysm include hemodynamically induced or degenerative vascular injury, atherosclerosis (typically leading to fusiform aneurysms), underlying vasculopathy (eg, fibromuscular dysplasia), and high-flow states, as in arteriovenous malformation (AVM) and fistula.
Uncommon causes include trauma, infection, drugs, and neoplasms (primary or metastatic).
Intracranial aneurysms are classified as follows:

• Saccular aneurysms
  

  • Developmental or degenerative
  • Traumatic
  • Mycotic
  • Oncotic
  • Flow-related
  • Vasculopathy-related
  • Drug-related
• Fusiform aneurysms
• Dissecting aneurysms

Saccular Aneurysms

Developmental/Degenerative Aneurysms

Pathology

Saccular aneurysms are rounded berrylike outpouchings that arise from arterial bifurcation points, most commonly in the circle of Willis (see image below). These are true aneurysms, ie, they are dilatations of a vascular lumen caused by weakness of all vessel wall layers.

A normal artery wall consists of 3 layers: the intima, which is the innermost endothelial layer; the media, which consists of smooth muscle; and the adventitia, the outermost layer, which consists of connective tissue. The aneurysmal sac itself is usually composed of only intima and adventitia. The intima is typically normal, although subintimal cellular proliferation is common. The internal elastic membrane is reduced or absent, and the media ends at the junction of the aneurysm neck with the parent vessel. Lymphocytes and phagocytes may infiltrate the adventitia. The lumen of the aneurysmal sac often contains thrombotic debris. Atherosclerotic changes in the parent vessel are also common.
Etiology
Most saccular or intracranial berry aneurysms were once thought to be congenital in origin, arising from focal defects in the media and gradually developing over a period of years as arterial pressure first weakens and subsequently balloons out the vessel wall.
Recent studies have found scant evidence for congenital, developmental, or inherited weakness of the arterial wall. Although genetic conditions are associated with increased risk of aneurysm development (see Associated conditions), most intracranial aneurysms probably result from hemodynamically induced degenerative vascular injury. The occurrence, growth, thrombosis, and even rupture of intracranial saccular aneurysms can be explained by abnormal hemodynamic shear stresses on the walls of large cerebral arteries, particularly at bifurcation points.
Less common causes of saccular aneurysms include trauma, infection, tumor, drug abuse (cocaine), and high-flow states associated with AVMs or fistulae.
Incidence
The true incidence of intracranial aneurysms is unknown but is estimated at 1-6% of the population.Published data vary according to the definition of what constitutes an aneurysm and whether the series is based on autopsy data or angiographic studies. In one series of patients undergoing coronary angiography, incidental intracranial aneurysms were found in 5.6% of cases, and another series found aneurysms in 1% of patients undergoing 4-vessel cerebral angiography for indications other than subarachnoid hemorrhage (SAH). Familial intracranial aneurysms have been reported. Whether this represents a true increased incidence is unclear.

Associated conditions

Congenital abnormalities of the intracranial vasculature, such as fenestrations of the vertebrobasilar junction or persistent trigeminal arteries, are associated with an increased incidence of saccular aneurysms. Fenestrations associated with saccular aneurysms have been found both at the fenestration site and on other, nonfenestrated vessels in the same patient. However, recent evidence indicates that the incidence of aneurysm at a fenestration site is not different from the typical association of other vessel bifurcations with saccular intracranial aneurysm.
Vasculopathies such as fibromuscular dysplasia (FMD), connective tissue disorders, and spontaneous arterial dissection are associated with an increased incidence of intracranial aneurysm.
Conditions that have been associated with increased incidence of cerebral aneurysms are as follows:

• Polycystic kidney disease
• Coarctation of the aorta
• Anomalous vessels
• FMD
• Connective tissue disorders (eg, Marfan, Ehlers-Danlos)
• High-flow states (eg, vascular malformations, fistulae)
• Spontaneous dissections

Autosomal dominant polycystic kidney disease (ADPKD) is by far the most common genetic abnormality associated with intracranial aneurysms, with an estimated 5-40% of ADPKD patients harboring such lesions. These lesions are often multiple. All patients with ADPKD should undergo screening using magnetic resonance angiography (MRA). The proper age to begin screening patients with ADPKD, as well as the frequency of rescreening (if the initial MRA findings are negative), are unresolved issues.
Screening for intracranial aneurysms is also recommended for people who have 2 immediate relatives with intracranial aneurysms.

Multiplicity

Intracranial aneurysms are multiple in 10-30% of all cases (see image below).About 75% of patients with multiple intracranial aneurysms have 2 aneurysms, 15% have 3, and 10% have more than 3. A strong female predilection is observed with multiple aneurysms. Although the overall female-to-male ratio is 5:1, the ratio rises to 11:1 in patients with more than 3 aneurysms.
 The circle of Willis has been dissected, and 3 berry aneurysms are observed. Multiple aneurysms are observed in about 20-30% of cases of berry aneurysm. Such aneurysms are congenital in the sense that the defect in the arterial wall may be present from birth, but the actual aneurysm develops over years, so rupture is most likely to occur in middle-aged adults. 

Multiple aneurysms are also associated with vasculopathies such as FMD and other connective tissue disorders.
Multiple aneurysms can be bilaterally symmetric (ie, mirror aneurysms) or located asymmetrically on different vessels. More than one aneurysm can be present on the same artery.
Aneurysms typically become symptomatic in people aged 40-60 years, with the peak incidence of SAH occurring in people aged 55-60 years.Intracranial aneurysms are uncommon in children and account for less than 2% of all cases. Aneurysms in the pediatric age group are often more posttraumatic or mycotic than degenerative and have a slight male predilection. Aneurysms found in children are also larger than those found in adults, averaging 17 mm in diameter.
Aneurysms commonly arise at the bifurcations of major arteries. Most saccular aneurysms arise on the circle of Willis (see images below) or the middle cerebral artery (MCA) bifurcation.
Common locations of cerebral saccular aneurysms. The relative incidences are shown

• Anterior circulation aneurysms: Approximately 86.5% of all intracranial aneurysms arise on the anterior (carotid) circulation. Common locations include the anterior communicating artery (30%), the internal carotid artery (ICA) at the posterior communicating artery origin (25%), and the MCA bifurcation (20%). The ICA bifurcation (7.5%) and the pericallosal/callosomarginal artery bifurcation account for the remainder (4%).
• Posterior circulation aneurysms: About 10% of all intracranial aneurysms arise on the posterior (vertebrobasilar) circulation. Seven percent arise from the basilar artery bifurcation, and the remaining 3% arise at the origin of the posterior inferior cerebellar artery (PICA) where it comes off of the vertebral artery.
• Miscellaneous locations: These lesions account for 3.5% of all lesions and involve sites such as the superior cerebellar artery and the anterior inferior cerebellar artery where they branch off the basilar artery. Saccular aneurysms are uncommon in locations other than the sites mentioned above. Aneurysms that develop at distal sites in the intracranial circulation are often caused by trauma or infection (see Traumatic aneurysms). Nontraumatic distal aneurysms, particularly along the anterior cerebral artery (ACA), have a high frequency of multiplicity and spontaneous hemorrhage.

Clinical presentation
Most aneurysms do not cause symptoms until they rupture; when they rupture, they are associated with significant morbidity and mortality.

• Subarachnoid hemorrhage
  

  • The most common presentation of intracranial aneurysm is subarachnoid hemorrhage (SAH; see images below). In North America, 80-90% of nontraumatic SAHs are caused by the rupture of an intracranial aneurysm. Another 5% are associated with bleeding from an AVM or tumor, and the remaining 5-15% are idiopathic. Remembering that trauma is overwhelmingly the most common cause of SAH is important, and a good history is often helpful in this regard. Increases in the number of patients taking antiplatelet or anticoagulant agents means that even a . minortrauma could result in SAH
  • The white arrow on the black card marks the site of a ruptured berry aneurysm in the circle of Willis. This is a major cause of subarachnoid hemorrhage. The subarachnoid hemorrhage from a ruptured aneurysm is more of anirritant-producing vasospasm than a mass lesion
  •   . Shown here is a CT scan of an aneurysmal subarachnoid hemorrhage. The CT scan in a 55-year-old woman shows subarachnoid blood within the interpeduncular and ambient cisterns and the right sylvian fissure caused by a ruptured aneurysm at the junction of the right carotid artery and theposterior communicating artery

   . A CT scan in an 82-year-old woman shows extensive subarachnoid blood within the cortical sulci, intraventricular hemorrhage, and an intracerebral hematoma adjacent to a large ruptured aneurysm of the anterior communicating artery.
  
  

  • On presentation, patients typically report experiencing the worst headache of their lives. The association of meningeal signs should increase suspicion of SAH. For a full description of the SAH, refer to the article Subarachnoid Hemorrhage.
  • Subhyaloid hemorrhages, often bilateral, located between the retina and vitreous membrane, may be observed in up to 25% of patients.
  • The most widely used clinical method for grading the clinical severity of SAH is the Hunt and Hess scale, which measures the clinical severity of the hemorrhage on admission and has been shown to correlate well with outcome, as follows:
    • Grade 0 - Unruptured aneurysm
    • Grade 1 - Asymptomatic or minimal headache and slight nuchal rigidity
    • Grade 2 - Moderate-to-severe headache, nuchal rigidity, no neurologic deficit other than cranial nerve palsy
    • Grade 3 - Drowsiness, confusion, or mild focal deficit
    • Grade 4 - Stupor, moderate-to-severe hemiparesis, possible early decerebrate rigidity, and vegetative disturbances
    • Grade 5 - Deep coma, decerebrate rigidity, and moribund appearance
  • The Fisher grade, which describes the amount of blood seen on a noncontrast head CT, is also useful in correlating the likelihood of developing vasospasm (discussed below), the most common cause of death and disability from SAH. Vasospasm is overwhelmingly most common in Fisher grade 3 and rarely found in patients with no blood on CT scan.
    • Fisher 1 - No blood detected
    • Fisher 2 - Diffuse or vertical layers less than 1 mm thick
    • Fisher 3 - Localized clot or vertical layer greater than or equal to 1 mm
    • Fisher 4 - Intracerebral or intraventricular clot with diffuse or no SAH
  • Other symptoms: Signs and symptoms of aneurysm other than those associated with SAH are relatively uncommon. Some intracranial aneurysms produce cranial neuropathies. A common example is the third nerve palsy that is secondary to posterior communicating artery aneurysm. Other, less common, symptoms include visual loss caused by an ophthalmic artery aneurysm that compresses the optic nerve, seizures, headaches, and transient ischemic attacks or cerebral infarction secondary to emboli (usually associated with large or giant partially thrombosed MCA aneurysms). The so-called giant aneurysms (diameter >2.5 cm) are more often symptomatic because of their mass effect. 

  
  Clinical outcome
  Vasospasm is the leading cause of disability and death from aneurysm rupture (see images below). Of patients with SAH, 10% die before reaching medical attention and another 50% die within one month. Fifty percent of survivors have neurological deficits. Ruptured aneurysms are most likely to rebleed within the first day (2-4%), and this risk remains very high for the first 2 weeks (about 25%) if left untreated. Early referral to a hospital that has physicians experienced in treating intracranial aneurysms, early treatment (open surgery and clipping or endovascular coiling), and aggressive treatment of vasospasm are 3 factors that have been correlated with improved outcomes.
  
  Outcomes associated with unruptured aneurysms are based primarily on whether they are treated and the results of that treatment.
  
  Natural history
  
  The risk of rupture among aneurysms that have not bled is unknown and, for many years, was believed to be 1-2% per year. Prior to the advent of endovascular coiling, most aneurysms were surgically treated via craniotomy (clipped) to prevent a future disastrous hemorrhage. A study (International Study of Unruptured Intracranial Aneurysms [ISUIA]) published in 1998 (retrospective component) and 2003 (prospective component) that involved 2621 and 1692 subjects, respectively, with intracranial aneurysms without intervention to determine the true natural history risk, has changed our current understanding of the natural history risk of aneurysms.
  Surprisingly, the study found that, for certain aneurysms, particularly those smaller than 7 mm and those located in the anterior circulation in patients who had not had a hemorrhage from another aneurysm, the risk of subsequent rupture was extremely small (0.05% per year in the retrospective and a 5-year cumulative risk of rupture of 0% in the prospective arm). Aneurysms at other locations (such as the basilar tip and the posterior communicating artery), aneurysms larger than 10 mm, and aneurysms that are found in patients who had bled from a prior aneurysm were found to have higher risks (about 0.5% per year). Despite these results, other recent reports continue to estimate the rupture risk for unruptured aneurysms at 1% per year.Critics of the ISUIA study emphasized that the selection was biased because surgeons who entered patients into the study felt that these aneurysms were less likely to bleed. Thus, the results of this study have significantly affected the way aneurysms are managed, with more and more aneurysms undergoing conservative management as opposed to invasive therapy, particularly if the aneurysms are small and asymptomatic.Untreated ruptured aneurysms have a very high risk of rebleeding after the initial hemorrhage. The risk is estimated at 20-50% in the first 2 weeks, and such rebleeding carries a mortality rate of nearly 85%. Aneurysms that have not ruptured but have manifested with other symptoms such as a new onset third nerve palsy (considered a true emergency that requires urgent treatment of the aneurysm), brain stem compression due to a giant aneurysm, or visual loss (caused by an ophthalmic artery aneurysm), for example, should be treated because the natural history risk of rupture is believed to be significantly higher (6% per year) than that of incidentally discovered lesions.Cigarette smoking, female sex, and younger age have recently been shown to correlate with aneurysm growth and rupture.
  The apex of vessel bifurcations is the site of maximum hemodynamic stress in a vascular network. Vascular and internal flow hemodynamics have a crucial effect on the origin, growth, and configuration of intracranial aneurysms. In the aneurysm, wall shear stress caused by the rapid changes of blood flow direction (the result of systole and diastole) continually damages the intima at an aneurysm cavity neck. These augmented hemodynamic stresses probably cause the initiation and subsequent progression of most saccular aneurysms. Thrombosis and rupture are also explained by intra-aneurysmal hemodynamic stresses.Studies demonstrate that the geometric relationship between an aneurysm and its parent artery is the principal factor that determines intra-aneurysmal flow patterns. In lateral aneurysms, such as those that arise directly from the ICA, blood typically moves into the aneurysm at the distal aspect of its ostium and exits at its proximal aspect, producing a slow-flow vortex in the aneurysm center. Opacification of the lumen then proceeds in a cranial-to-caudal fashion. Contrast stagnation within these aneurysms is often pronounced.
  In contrast to lateral aneurysms, intra-aneurysmal circulation is rapid, and vortex formation with contrast stasis is rare when aneurysms arise at the origin of branching vessels or a terminal bifurcation. These patterns of intra-aneurysmal flow are important not only for the formation and progression of an aneurysm itself but also because they may influence the selection and placement of endovascular treatment devices.
  In giant saccular aneurysms (>2.5 cm), slow growth can occur by recurrent hemorrhages into the lesion. The highly vascularized membranous wall of giant intracranial aneurysms is the most likely source of these intra-aneurysmal hemorrhages. Giant sacs commonly contain multilayered laminated clots of varying ages and consistency. The outer wall is fibrous and thick. These multilaminated giant aneurysms seldom rupture into the subarachnoid space and typically produce symptoms related to their mass effect.
  

  Traumatic Aneurysms

  Traumatic aneurysms account for less than 1% of all aneurysms. The following 2 general types of traumatic aneurysms are identified: aneurysms secondary to penetrating trauma and aneurysms secondary to nonpenetrating trauma.
  
  Penetrating trauma
  
  Intracerebral aneurysms secondary to penetrating injuries are commonly due to high-velocity missile wounds of the head. A recent study demonstrated a 50% overall prevalence of major vascular lesions in civilian patients with penetrating missile injuries examined in the acute stage. Nearly half of these patients had traumatic aneurysms. The diagnosis of posttraumatic aneurysm may be delayed or overlooked on CT scan because the lesion is often obscured by the presence of an accompanying hemorrhagic intraparenchymal contusion.
  Penetrating injuries to extracranial vessels can cause lacerations, arteriovenous fistulae, dissection, or traumatic pseudoaneurysm. The carotid artery is the most frequently involved vessel. Pathologically, a false aneurysm lacks any components of a vessel wall. These false aneurysms, or pseudoaneurysms, are really cavities, typically within adjacent blood clots, that communicate with a vessel lumen. Radiographically, a false aneurysm projects beyond the vessel margin into the adjacent soft tissues. The periadventitial hematoma can be delineated on CT scan or magnetic resonance (MR) studies.
  Occasionally, the external carotid artery is a site of traumatic injury. The superficial temporal artery (STA) is the most commonly affected vessel. STA traumatic pseudoaneurysm occurs as a complication of scalp trauma and may result from penetrating injury or blunt trauma.
  Meningeal vessels are uncommon sites of traumatic pseudoaneurysm development; most occur on branches of the middle meningeal artery. When a meningeal pseudoaneurysm hemorrhages, it is usually into the epidural space. Direct penetrating injury to the vertebral artery (VA) is uncommon. Occasionally, cervical spine fracture-dislocations damage the VA. These typically produce dissection or occlusion; pseudoaneurysms are rare.
  
  Nonpenetrating trauma
  
  Intracranial aneurysm secondary to nonpenetrating trauma is rare and usually occurs at the skull base (where it involves the petrous, cavernous, or supraclinoid ICA) or along the peripheral intracranial vessels. ICA aneurysms at the skull base can be caused by blunt trauma or skull fracture. Hyperextension and head rotation may stretch the ICA over the lateral mass of C1 or shear the artery at its intracranial entrance.
  Peripheral intracranial aneurysms can be caused by closed head injury. The distal anterior cerebral artery and peripheral cortical branches are commonly involved sites distal to the circle of Willis. Frontolateral impacts produce shearing forces between the inferior free margin of the falx cerebri and the distal ACA. This can cause a common type of nonpenetrating traumatic intracranial aneurysm, a traumatic aneurysm of the pericallosal artery. Suspect the presence of a traumatic distal ACA aneurysm if a juxtafacial hematoma is observed on CT scan.
  Suspect traumatic cortical artery aneurysm if a delayed hematoma near the brain periphery develops adjacent to the site of a skull fracture.
  
  Treatment
  
  Although cases have been reported to resolve spontaneously, direct treatment is usually recommended. Such aneurysms can usually be approached either surgically (clipping) or endovascularly (coiling), depending on the location. For aneurysms located proximally near the skull base, balloon-test occlusion and parent vessel sacrifice may be an option. For distal aneurysms, coiling or clipping with vascular bypass (if important branch vessels are incorporated into the aneurysm neck) may both be considered.
  

  Mycotic Aneurysms

  The term mycotic aneurysm refers to any aneurysm that results from an infectious process that involves the arterial wall. These aneurysms may be caused by a septic cerebral embolus that causes inflammatory destruction of the arterial wall, beginning with the endothelial surface. A more likely explanation is that infected embolic material reaches the adventitia through the vasa vasorum. Inflammation then disrupts the adventitia and muscularis, resulting in aneurysmal dilatation.
  Mycotic aneurysms were once estimated to account for 2-3% of all intracranial aneurysms but were described as decreasing in the antibiotic era. However, with the increased incidence of drug abuse and immunocompromised states from various causes, mycotic aneurysms may have increased in frequency.The thoracic aorta has been described as the most common site of mycotic aneurysm. Intracranial mycotic aneurysms are less common. They occur with greater frequency in children and are often found on vessels distal to the circle of Willis. Rarely, deep neck space infections are complicated by pseudoaneurysm of the cervical ICA.
  
  Treatment
  
  Mycotic aneurysms generally have a fusiform morphology and are usually very friable. Therefore, treatment is difficult or risky. Most cases are treated emergently with antibiotics, which are continued for 4-6 weeks. Serial angiography (at 1.5, 3, 6, and 12 mo) helps document the effectiveness of medical therapy. Even if aneurysms seem to be shrinking, they may subsequently grow, and new ones may form.
  Serial MRA may be a viable alternative in some cases. Aneurysms may continue to shrink following completion of antibiotic therapy. Delayed clipping or coiling may be more feasible; indications include patients with SAH, increasing size of aneurysm while on antibiotics (this is controversial; some argue that this is not mandatory), and failure of the aneurysm to shrink after 4-6 weeks of antibiotics. Patients with subacute bacterial endocarditis who require valve replacement should have bioprosthetic (ie, tissue) valves instead of mechanical valves to eliminate the need for risky anticoagulation.
  

  Oncotic Aneurysms

  Extracranial oncotic pseudoaneurysms with exsanguinating epistaxis are a common terminal event with malignant head and neck tumors. Intracranial oncotic aneurysms are less common. They are often bizarre-shaped and on distal branches of the intracranial vessels, remote from the more typical saccular aneurysms located on the circle of Willis. Such aneurysms may be associated with either primary or metastatic tumors. Neoplastic aneurysms result from direct vascular invasion by a tumor or implantation of metastatic emboli that infiltrate and disrupt the vessel wall. Myxomatous aneurysms are one type of oncotic intracranial aneurysm that are associated with atrial myxomas in a small percentage of cases.
  Endovascular treatment using balloon-test occlusion (to determine whether the patient can tolerate vessel sacrifice), followed by intentional vessel occlusion (if the patient passes the test), is one common way to treat such aneurysms. Stent-assisted coiling, in which a porous stent is placed across the aneurysm and is followed by filling the aneurysm with coiling, is another option. Emergent treatment with a covered stent (graft stent) has been used to avert life-threatening intracranial bleeding.
  
  See the images below.
  
  CT angiography reconstruction showing a large irregularly shaped presumed mycotic middle cerebral artery aneurysm.
    Coronal CT angiography showing a large irregularly shaped presumed mycoticmiddle cerebral artery aneurysm (see previous image).
    Digital subtraction angiogram, right internal carotid injection, showing a large irregularly shaped presumed mycotic middle cerebral artery aneurysm.
   Digital subtraction angiogram, right internal carotid injection, 3-dimensional reconstruction, showing a large irregularly shaped presumed mycotic middle cerebral artery aneurysm (see previous image).
  
  Primary tumors
  
  Intracranial aneurysms associated with primary brain tumors are less common than those caused by metastases. The incidence of saccular aneurysms in patients with primary cerebral neoplasms does not appear to be significantly higher than the incidence of aneurysms in the general population, although some authors report a slightly higher incidence with meningiomas.
  
  Metastatic tumors
  
  Some metastatic tumors that have been implicated in the development of intracranial aneurysm include left atrial myxoma and choriocarcinoma. Because metastatic tumors are common at the gray-white junction, aneurysms due to metastatic implants often involve peripheral cerebral vessels.
  

  Flow-Related Aneurysms

  The coexistence of AVMs and aneurysms is well known. The frequency of aneurysms with AVM has been reported as 2.7-30%. Flow-related aneurysms occur along proximal and distal feeding vessels. Proximal lesions arise in the circle of Willis or on vessels that feed the AVM and are probably related to increased hemodynamic stress. No increased frequency of hemorrhage is reported in patients with proximal feeding-artery aneurysms.
  Distal flow-related aneurysms are located in distal branches to the AVM. Intranidal aneurysms have been reported in 8-12% of AVMs. These lesions are thin-walled vascular structures without the elastic or muscular layers that characterize arteries. Whether intranidal aneurysms arise from venous ectasias (dilatation) or from the flow-weakened walls of arterial vessels is unclear. Nevertheless, these thin-walled structures are exposed to arterial pressure and are considered a likely site for AVM hemorrhage.
  Treatment of aneurysms associated with AVMs is similar to that of aneurysms not associated with AVMs, with the following differences:
  

  • Small flow-related aneurysms have been shown to disappear or shrink after successful treatment of the AVM, and this possibility must be considered, particularly if no hemorrhage has occurred.
  • AVMs that bleed often have intra-nidal aneurysms; when these are found, they should be targeted for urgent therapy secondary to their presumed ability to rebleed with increased frequency.
  • In AVMs that manifest as SAH and circle of Willis aneurysms, presume that the aneurysm (not the AVM) is the source of the SAH and treat urgently to prevent rebleeding.

  Vasculopathy-Related, Vasculitis-Related, and Drug-Related Aneurysms

  Some vasculopathies, such as FMD (see Multiplicity), have an increased incidence of cephalocervical aneurysms. Some vasculitides, such as systemic lupus erythematosus (SLE) and even Takayasu arteritis, have been associated with aneurysms. Substance abuse, especially with cocaine, can cause certain forms of vasculitis that contribute to aneurysm formation or can cause hemorrhage from preexisting vascular abnormalities such as AVMs or saccular aneurysms because of their ability to cause sudden rapid surges of increased systemic blood pressure to high values.
  

  Vasculopathies

  • SLE: Commonly reported CNS vascular lesions with SLE include infarcts and transient ischemic attacks. Intracranial hemorrhages are present in approximately 10% of patients with CNS symptoms. Although uncommon, arteritic and nonvasculitic aneurysms occur in SLE. These can be saccular, fusiform, or a bizarre-looking mixture of both.
  • Takayasu arteritis: The characteristic vascular lesions include occlusion, stenosis, and luminal irregularities, but ectasia and aneurysm formation have been described in Takayasu arteritis.
  • FMD: Some investigators report a 20-50% incidence of aneurysms in patients with cervical FMD. Other abnormalities associated with FMD include spontaneous dissection, dissecting aneurysm (see Dissecting Aneurysms), and arteriovenous fistulae.
  • Drug abuse: Various intracranial vascular lesions have been reported with substance abuse.
    

    • Cocaine abuse is associated with various CNS complications, including SAH, cerebral ischemia or infarction, intraparenchymal hemorrhage, seizures, vasculitis, vasospasm, and death. Approximately 50% of patients who have a drug abuse problem along with CNS symptoms have SAH; of these, about half have an underlying abnormality such as aneurysm or vascular malformation. Hemorrhage may also be related to the acute hypertensive response that occurs with cocaine use.
    • Heroin, ephedrine, and methamphetamine use can cause cerebral vasculitis. Necrotizing angiitis, histologically similar to periarteritis nodosa, has been identified in patients who abuse methamphetamines. Focal arterial ectasias, aneurysms, and sacculations have been reported in this form of drug-induced cerebral arteritis. 
    
    

    Fusiform Aneurysms

    Pathology

    Fusiform aneurysms are also known as atherosclerotic aneurysms. These lesions are exaggerated arterial ectasias that occur because of a severe and unusual form of atherosclerosis. Damage to the media results in arterial stretching and elongation that may extend over a considerable length. These ectatic vessels may have more focal areas of fusiform or even saccular enlargement. Intraluminal clots are common, and perforating branches often arise from the entire length of the involved parent vessel.
    

    Clinical presentation

    Fusiform aneurysms usually occur in older patients. The vertebrobasilar system is commonly affected. Fusiform aneurysms may thrombose, producing brainstem infarction as small ostia of perforating vessels that emanate from the aneurysm become occluded. They can also compress the adjacent brain or cause cranial nerve palsies.
    

    Imaging

    Fusiform atherosclerotic aneurysms usually arise from elongated tortuous arteries. Patent aneurysms enhance strongly after contrast administration; thrombosed aneurysms are hyperintense on noncontrast CT scans. Tubular calcification with intraluminal and mural thrombi in the ectatic parent vessels and aneurysm wall is common. Occasionally, fusiform aneurysms cause erosion of the skull base.
    On angiography, fusiform aneurysms often have bizarre shapes, with serpentine or giant configurations. Intraluminal flow is often slow and turbulent. These aneurysms typically do not have an identifiable neck. MRI is helpful in delineating the relationship between vessels and adjacent structures such as the brainstem and cranial nerves.

    Dissecting Aneurysms

    Pathology

    In arterial dissections, blood accumulates within the vessel wall through a tear in the intima and internal elastic lamina. The consequences of this intramural hemorrhage vary. If blood dissects subintimally, it causes luminal narrowing or even occlusion. If the intramural hematoma extends into the subadventitial plane, a saclike outpouching may be formed (see image below). Do not confuse these focal aneurysmal dilatations with the pseudoaneurysms that result from arterial rupture and subsequent encapsulation of the perivascular hematoma. Thus, uncomplicated dissections do not project beyond the lumen of the parent vessel, and dissections with saclike outpouchings are termed dissecting aneurysms. The term false saccular aneurysm, or pseudoaneurysm, should be used for encapsulated, cavitated, paravascular hematomas that communicate with the arterial lumen.
    

    Etiology

    Dissecting aneurysms may arise spontaneously. More commonly, trauma or an underlying vasculopathy such as FMD is implicated.
    

    Location

    Most dissecting aneurysms that involve the craniocerebral vessels affect the extracranial segments; intracranial dissections are rare and usually occur only with severe head trauma. Although the common carotid artery (CCA) can be involved by cephalad extension of an aortic arch dissection, the CCA and carotid bulb are usually spared. The ICA is commonly affected. Most dissections involve the midcervical ICA segment and terminate at the extracranial opening of the petrous carotid canal.
    The VA is also a common site of arterial dissection. The common location is between the VA exit from C2 and the skull base. Involvement of the first segment, which extends from the VA origin to its entry into the foramen transversarium (usually at the C6 level), is relatively rare.
    

    Imaging

    Dissecting aneurysms are elongated, ovoid, or saccular contrast collections that extend beyond the vessel lumen. MR studies delineate an intravascular or perivascular hematoma associated with dissections, particularly during the subacute stage. MRA is a helpful screening procedure, but catheter angiography is the procedure of choice for imaging vessel details such as dissection site.

    Imaging of Intracranial Aneurysms

    Imaging Overview

    The 3 major modalities used to reveal and study the size, location, and morphology of an intracranial aneurysm include thin-section CT scanning after an intravenous injection using special computer software (CT angiography [CTA]; see first image below), MRA (see second image below), and catheter angiography (see the final 3 images below). The preferred initial method for evaluation of unruptured intracranial aneurysms is either MRA or CTA, whereas angiography is the preferred modality in patients who have had a subarachnoid hemorrhage (SAH), although CTA alone has been used.

  
  
  

 

Hemangioblastoma

Background

In 1928, Cushing and Bailey introduced the term hemangioblastoma.  It refers to a benign vascular neoplasm that arises almost exclusively in the central nervous system. According to the World Health Organization classification of tumors of the nervous system, hemangioblastomas are classified as meningeal tumors of uncertain origin.

Supratentorial hemangioblastoma proved by histologic analysis. Carotid arteriogram demonstrates a vascular, dense, tumor filled from the anterior cerebral vessels and not involving the sagittal sinus. 

Supratentorial hemangioblastoma proved by histologic analysis. Carotid arteriogram demonstrates a vascular, dense, tumor filled from the anterior cerebral vessels and not involving the sagittal sinus.

History of the Procedure

Since its original description, hemangioblastomas have been found in multiple regions of the central nervous system. Predominant involvement of the cerebellum and the spinal cord was noted, but true incidence of this tumor was not discovered until the recent increased availability of noninvasive diagnostic imaging modalities, particularly magnetic resonance imaging. This, in addition to significant improvement in surgical approaches and microsurgical technique, have made hemangioblastoma, although dangerous, a potentially treatable and curable disease. 

Epidemiology

Frequency

Incidence and location

Hemangioblastomas are rare, and according to various series, they account for 1-2.5% of all intracranial neoplasms.Most hemangioblastomas are located in the posterior cranial fossa; in that region, hemangioblastomas comprise 8-12% of neoplasms. Hemangioblastoma is the most common primary adult intraaxial posterior fossa tumor. Cerebellar hemangioblastomas are frequently referred to as Lindau tumors because Swedish pathologist Arvid Vilhelm Lindau first described them in 1926.
The second most common location of hemangioblastomas is the spinal cord, where the frequency ranges from 2-3% of primary spinal cord neoplasms to 7-11% of spinal cord tumors. This tumor's occurrence in other locations, such as the supratentorial compartment, the optic nerve,the peripheral nerves,or the soft tissues of extremities is extremely rare.

Sex and age distribution

Hemangioblastomas are more common in men than in women. In most clinical series, the male-to-female ratio is approximately 2:1. Although hemangioblastomas may develop at any age, they rarely affect children; the usual age at diagnosis is between the third and fifth decades.

von Hippel-Lindau disease

Most hemangioblastomas arise sporadically. However, in approximately one quarter of all cases, they are associated with von Hippel-Lindau (VHL) disease, an autosomal dominant hereditary syndrome that includes retinal angiomatosis, central nervous system hemangioblastomas, and various visceral tumors most commonly involving the kidneys and adrenal glands.This syndrome is classified as a phakomatosis, although it does not include any cutaneous manifestations. The syndrome has variable penetrance, but its dominant mode of transmission compels performing at least a screening of family members of patients diagnosed with VHL disease. In some patients with VHL disease, hemangioblastomas may produce erythropoietinlike substances, resulting in polycythemia at the time of diagnosis.

Etiology

Etiology of the hemangioblastoma is obscure, but its presence in various clinical syndromes may suggest an underlying genetic abnormality. The genetic hallmark of hemangioblastomas is the loss of function of the von Hippel-Lindau (VHL) tumor suppressor protein.

Pathophysiology

Upon gross examination, hemangioblastomas are usually cherry red in color. They may include a cyst that contains a clear fluid, but solid tumors are as common as cystic ones. The tumor usually grows inside the parenchyma of the cerebellum, brain stem, or spinal cord; it is attached to the pia mater and gets its rich vascular supply from the pial vessels. However, extramedullary and extradural hemangioblastomas also have been described.

Presentation

The clinical presentation of hemangioblastomas usually depends on the anatomical location and growth patterns. Cerebellar lesions may present with signs of cerebellar dysfunction, such as ataxia and discoordination, or with symptoms of increased intracranial pressure due to associated hydrocephalus.
In general, intracranial hemangioblastomas present with a long history of minor neurological symptoms that, in most cases, are followed by a sudden exacerbation, which may necessitate immediate neurosurgical intervention.Patients with spinal cord lesions most frequently present with pain, followed by signs of segmental and long-track dysfunction due to progressive compression of the spinal cord.
Patients with VHL disease may present with ocular or systemic symptoms due to involvement of other organs and systems.The polycythemia that may develop in some patients with hemangioblastomas usually is clinically asymptomatic.Spontaneous hemorrhage is possible in both intraspinal and intracranial hemangioblastomas, but this risk is low and tumors smaller than 1.5 cm carry virtually no risk of spontaneous hemorrhage.

Indications

In many cases, symptoms caused by the growth of the neoplasm itself may be an indication for surgical intervention. In others, symptomatic obstruction of the cerebrospinal fluid (CSF) pathways may necessitate the operation. Asymptomatic lesions that sometimes are encountered in patients with multiple hemangioblastomas may be safely observed with frequent MRI scans to rule out tumor enlargement.

Relevant Anatomy

Presence of a hemangioblastoma rarely, if ever, alters normal anatomy. In choosing the appropriate surgical approach to the tumor, one must take into consideration the position of the mass, presence (or absence) of a large cystic component, associated hydrocephalus and surrounding edema, and the eloquence of neighboring neural and vascular structures. In most cases, cerebellar lesions may be removed through a suboccipital craniectomy, whereas spinal lesions are best addressed from a posterior direction through a laminectomy approach.

Contraindications

As always, surgical resection should be offered to the patient unless the risk of operation outweighs its potential benefits. Acute anticoagulation, the presence of active systemic infection, and severe medical problems that would make general anesthesia too risky generally are considered contraindications for an elective neurosurgical operation. However, the decision should be made on an individual basis.

Hemangioblastoma Workup

 

Laboratory Studies

• Perform blood tests to help reveal associated lesions that may be a part of the VHL disease complex. Unfortunately, finding polycythemia does not help in diagnosing the tumor.

Imaging Studies

• The diagnostic workup of suspected hemangioblastomas must include, in addition to history, physical, and thorough neurological examination, complete neural axis imaging and abdominal CT scan or ultrasound. The goal of these additional tests is to reveal associated lesions that may be a part of VHL disease complex.
• Radiographically, hemangioblastomas are best diagnosed with MRI. MRI of hemangioblastomas usually shows an enhancing mass clearly delineated from the surrounding brain or spinal cord tissue. The tumor tissue may be hypointense or isointense on precontrast T1-weighted images and hyperintense on T2-weighted images.
• Plain radiographs usually do not aid in diagnosis. Myelography and cisternography, which were considered the tests of choice in the past, now are almost never used in the diagnostic workup of hemangioblastomas.
• Plain computed tomography (CT) scan may reveal hypodensity of the tumoral cyst and associated hydrocephalus. CT scans with intravenous contrast show uniform enhancement of the tumor nodule that, in association with the adjacent cyst, may be extremely characteristic of posterior fossa hemangioblastomas.
• Cerebral and spinal angiography reveals a highly vascular tumor blush, and this diagnostic modality may be extremely useful for assessing the vascular supply to the tumor. This information may help the surgeon during tumor resection.
• In patients with hemangioblastomas, complete neural axis imaging usually is recommended in order to rule out multiple lesions, especially in those cases in which VHL syndrome is either diagnosed or clinically suspected.

Other Tests

• Perform a detailed ophthalmologic evaluation to help reveal associated lesions that may be a part of the VHL disease complex.

Histologic Findings

Histologically, hemangioblastomas are vascular neoplasms. In addition to relatively normal-appearing endothelial cells that line capillary spaces, hemangioblastomas have 2 distinct cellular components that may occur in the same tumor in different proportions. The first type is small, perivascular, endothelial cells that have dark compact nuclei and sparse cytoplasm. Cells of the second type contain multiple vacuoles and granular eosinophilic cytoplasm rich in lipids. These stromal cells may show some nuclear pleomorphism, but mitotic figures rarely are seen. The exact histogenetic origin of stromal cells is unknown, but the latest studies indicate that they may represent a heterogeneous population of abnormally differentiating mesenchymal cells of angiogenic lineage, with some morphological features of endothelium, pericytes, and smooth-muscle cells.^[
Two histological subtypes (cellular and reticular) have been described in primary hemangioblastomas of the central nervous system and have been found to correlate with the probability of tumor recurrence. The reticular subtype is more commonly encountered; the cellular subtype is associated with higher probability of recurrence.
No histologic grading system exists for hemangioblastomas.

Staging

No established histologic grading system exists for hemangioblastomas.

Hemangioblastoma Treatment & Management

Medical Therapy

Because hemangioblastomas are benign tumors and generally are not invasive in nature, they may be cured by surgical excision. Therefore, surgical resection is considered a standard of treatment and should be offered to the patient unless the risk of operation outweighs its potential benefits.
Other therapeutic modalities include endovascular embolization of the solid component of the tumor,which may decrease the vascularity of the tumor and lower blood loss during its resection, and stereotactic radiosurgery of the tumor using either a linear accelerator or a Gamma Knife.Antiangiogenic treatment of hemangioblastoma has also been recently described.

Surgical Therapy

Surgical treatment of hemangioblastomas is total resection, with the main goal being the preservation of surrounding neural tissue.The tumors usually are well demarcated from the surrounding brain or spinal cord, but this border of separation does not contain any particular membrane or capsule.
The surgical approach must be wide enough to avoid compression of the healthy tissues during retraction. Thorough evaluation of preoperative imaging studies is the key to the safest possible exposure of the tumor. In addition to MRI and CT scans, review the angiography findings to identify the principal blood supply to the tumor mass.

Preoperative Details

Prior to surgery, patients should undergo adequate medical evaluation and complete neural axis imaging. Patients and their families must be informed about the risks and possible complications of surgery, particularly the potential for neurological deterioration.

Intraoperative Details

The tumor is usually easy to visualize because of its reddish-colored solid component and the yellow fluid inside the cyst.If the cyst is present, it may be emptied by cutting the covering pial membrane or by aspirating the cystic contents using a syringe with a short small-caliber needle. Decompression of the cyst allows for improved delineation of the interface between the tumor and the brain or spinal cord.
The surface of the tumor may be coagulated with wide bipolar forceps; however, avoid penetration of the tumor itself because of its extreme vascularity and difficulties with hemostasis. Try to dissect the tumor circumferentially by careful coagulation and cutting the small feeding vessels and adhesions between the tumor and the surrounding brain or spinal cord and by putting cottonoid strips into the developing plane to avoid direct pressure on the brain or spinal cord tissue.Once the feeding vessels are identified, they are coagulated and cut. Try to coagulate the arterial feeders prior to the draining veins, but this is not as crucial as it is in arteriovenous malformations.
After the tumor is totally removed, the raw surface of the brain or spinal cord remains relatively bloodless, and the oozing blood stops after a few minutes of gently packing the resection cavity with wet cotton balls, avoiding the need for additional coagulation.
If an associated hydrocephalus exists, it must be addressed separately, usually by means of external ventricular drainage (EVD) prior to tumor resection. After the tumor is removed, the need for permanent shunt placement may be determined by the patient's response to EVD clamping. In most cases, an intramedullary syrinx does not require a separate drainage procedure because it usually resolves after tumor removal.

Postoperative Details

In regards to general surgical management, having blood products available for transfusion is very important because the vascular character of hemangioblastomas may result in serious intraoperative blood loss. Additionally, anesthesia for patients with VHL disease may be quite challenging due to the presence of associated renal and endocrine dysfunction.

Follow-up

Follow-up care for patients with hemangioblastomas should include regular neurological and imaging checks to confirm the absence of tumor recurrence and/or development of distant lesions.

Complications

With an adequate preoperative workup, most complications of surgery for hemangioblastoma may be avoided. Meticulous maintenance of hemostasis, attention to minor details, and great respect for neural and vascular elements may significantly decrease the risk of postoperative complications. The main emphasis, as usual, should be placed on preventing complications rather than on treatment.

Outcome and Prognosis

Long-term results of hemangioblastoma management generally are favorable. Advancement of neuroimaging methods, improvements in microsurgical technique, and the addition of preoperative embolization have significantly lowered morbidity and mortality associated with hemangioblastoma surgery.
Subarachnoid dissemination of hemangioblastomas is extremely rare, and local recurrences after complete tumor resection seem to be more frequent in patients with von Hippel-Lindau (VHL) disease, in patients diagnosed at a young age, and in patients with multiple hemangioblastomas. The results of one study found that resection of brainstem hemangioblastomas is generally a safe and effective treatment for patients with VHL disease. However, due to VHL disease–associated progression, long-term decline in functional status may occur. The recurrence rate varies in different surgical series but generally remains less than 25%. Recently, histological subtype was found to correlate with a probability of hemangioblastoma recurrence, with a 25% recurrence rate in cellular subtype and an 8% recurrence rate in reticular subtype.

Conclusion

Hemangioblastomas are benign tumors of uncertain origin that are located predominantly in the posterior cranial fossa and the spinal cord. Although most hemangioblastomas are sporadic, they are associated with autosomally dominant VHL disease in approximately 25% of cases. The tumors may be solid or cystic, and patients usually present with either focal neurological symptoms or increased intracranial pressure due to obstruction of CSF pathways. Most hemangioblastomas can be cured with surgical resection, and long-term recurrence rates seem to depend on the presence of VHL disease and multicentric lesions.

Future and Controversies

Future treatment of hemangioblastoma will greatly depend on gaining an understanding of its genetic background. Obviously, if identifying a genetic defect responsible for tumor formation and growth becomes possible, this defect could be reversed and tumor growth could be prevented. Also, finding specific genetic and molecular targets in hemangioblastomas may enable treatment using nonsurgical means, with higher success rates and lower risks of complications.

 Photomicrograph shows the classic microscopic appearance of a cerebellar hemangioblastoma with numerous capillaries and polygonal stroma cells shows vacuoles of cytoplasm and hyperchromatic nucleus (hematoxylin-eosin stain, high-power magnification).