Headache, nausea and vomiting are symptoms that are most frequently reported, as well as altered consciousness [6]. Swelling of the optic disc (papilledema) that causes blurred vision may be frequently encountered, but it is rarely present in patients with head injury [1]. Unfortunately, patients often present in comatose states and symptoms may not always be present. Various neurological deficits, including hemiparesis, ophtalmoplegia and cranial nerve palsies may be encountered, while respiratory changes that leads to either hyper or hypocapnia, as well as fever, can be present.

• Pathologist

  This examination, performed by a pathologist, typically has three stages: interoperative examination of fresh tissue, preliminary microscopic examination of prepared tissues, and follow-up examination of prepared tissues after immunohistochemical staining [en.wikipedia.org]

• Sneezing

  […] may be worse in the morning, or when coughing or straining; it may improve when standing up blurred or double vision temporary loss of vision – your vision may become dark or "greyed out" for a few seconds at a time; this can be triggered by coughing, sneezing [nhs.uk]

  The headache is worse on coughing, sneezing or bending and progressively worsens over time. [en.wikipedia.org]

• Nausea

  A previously well 12-year-old boy presented with a 2-week history of headache, nausea, vomiting and left-sided weakness. [ncbi.nlm.nih.gov]

  Headache, nausea and vomiting are symptoms that are most frequently reported, as well as altered consciousness. [symptoma.com]

  Symptoms of pseudotumor cerebri, which include headache, nausea, vomiting, and pulsating sounds within the head, closely mimic symptoms of large brain tumors. [ninds.nih.gov]

  By Allison, United States, February 17, 2015 Three years ago I began to experience severe daily headaches, nausea and vertigo. [rarediseaseday.org]

• Vomiting

  It is a poorly understood syndrome that most commonly manifests nonspecific symptoms such as stroke-like headache, vision changes, nausea, vomiting, and papilledema. [ncbi.nlm.nih.gov]

  Headache, nausea and vomiting are symptoms that are most frequently reported, as well as altered consciousness. [symptoma.com]

  Symptoms of pseudotumor cerebri, which include headache, nausea, vomiting, and pulsating sounds within the head, closely mimic symptoms of large brain tumors. [ninds.nih.gov]

  Aside from the worsening headaches and vision, she denied other signs or symptoms such as a change in weight, fevers, chills, night sweats, nausea, vomiting, chest pain, dyspnea, incontinence, or abdominal pain. [jaoa.org]

• Hypertension

  Idiopathic intracranial hypertension. Brain. 1991;114:155-80. Wall M. The headache profile of idiopathic intracranial hypertension. Cephalalgia. 1990;10:331-35. Corbett JJ, Thomson HS. The rational management of idiopathic intracranial hypertension. [rarediseases.org]

  Keywords: Papilledema; Idiopathic intracranial hypertension; Pseudotumorcerebri; Benign intracranial hypertension; Optic neuropathy Introduction Idiopathic intracranial hypertension, also known as pseudotumorcerebri (PTC) orbenign Intracranial Hypertension [austinpublishinggroup.com]

  How is pediatric idiopathic intracranial hypertension diagnosed? If idiopathic intracranial hypertension is suspected, an ophthalmologist usually examines the optic nerve for swelling (papilledema). [aapos.org]

• Contusion

  […] hypertension are numerous and include: Intracranial diseases - Brain tumors (either primary or metastatic disease), cerebrovascular insults (ischemic stroke, intracerebral hemorrhage), trauma that leads to epidural or subdural hematomas, as well as cerebral contusions [symptoma.com]

  […] is in the case of papilledema that vision may go largely unaffected. [12] Causes [ edit ] Causes of increased intracranial pressure can be classified by the mechanism in which ICP is increased: Mass effect such as brain tumor, infarction with edema, contusions [en.wikipedia.org]

  In a first group of 53 patients, a P‐DC was performed when generalized brain edema was evident during surgery indicated for removal of space‐occupying lesions (subdural, epidural hematoma, brain contusion, etc.). [cochranelibrary.com]

• Diplopia

  In the following 2 months, he gradually developed hoarseness and diplopia at the left and lower fields of vision. A brain MRI revealed wide-spread fattening and meningeal enhancement over the left hemisphere and the left cerebellar hemisphere. [ncbi.nlm.nih.gov]

  Idiopathic intracranial hypertension (IIH)—also known as pseudotumor cerebri —is a neurologic condition that can manifest as headache, increased cerebrospinal fluid (CSF) pressure, papilledema, vision loss, diplopia, tinnitus, deafness, nausea and vomiting [jaoa.org]

  […] disorder, which has also been referred to in the medical literature as pseudotumor cerebri (PTC) and benign intracranial hypertension (BIH), produces symptoms that are similar to a large brain tumor, which can include: Blurred vision Double vision (diplopia [schmidtandclark.com]

• Anisocoria

  At the beginning of uncal herniation, indicated by anisocoria, the mean 1-CBF of the IC abruptly decreased from 33.7 to 19.6 ml/100g/min (n=16). In this stage, the pressure gradient between the supra- and infratentorial spaces was 24.6±11.4 mmHg. [ousar.lib.okayama-u.ac.jp]

• Vertical Gaze Palsy

  Examination of the oculomotor nerves may reveal difficulty moving the eyes vertically up or horizontally and laterally. Vertical gaze palsy is the result of pressure on the roof midbrain, where vertical gaze centers are located. [clinicaladvisor.com]

• Retinal Hemorrhage

  Funduscopic exam findings including: papilledema, loss of venous pulsations and retinal hemorrhages. 4. Seizures. 5. Cushing's triad or physiology, which includes irregular respirations, systemic arterial hypertension and bradycardia. [clinicaladvisor.com]

• Headache

  Migraine With Aura - the Basics Migraine Without Aura - the Basics New Daily Persistent Headache - The Basics Orgasmic and Preorgasmic Headache - The Basics Paroxysmal Hemicrania - The Basics Post-Traumatic Headache - The Basics Primary Exertional Headache [healthcentral.com]

  Headache. 2006; 46 (8):1255-1260. doi:10.1111/j.1526-4610.2006.00527.x. [CrossRef] [PubMed] [jaoa.org]

  The syndrome of headache with neurologic deficits and cerebrospinal fluid lymphocytosis (HANDL) is rare; it comprises migrainous headaches (generally in headache-naïve people), fluctuating neurological symptoms and cerebrospinal fluid (CSF) lymphocytosis [ncbi.nlm.nih.gov]

  Headache diagnoses in patients with treated idiopathic intracranial hypertension. Neurology. 2002;58:1551-3. Digre KB. Idiopathic intracranial hypertension headache. Curr Pain Headache Rep. 2002;6:217-25. Shin RK, Balcer LJ. [rarediseases.org]

• Papilledema

  On discontinuing the drug, the papilledema resolved over 4 months without any residual visual anomalies. To the best of our knowledge, this is the first report of fluvoxamine-induced intracranial hypertension with papilledema. [ncbi.nlm.nih.gov]

  If idiopathic intracranial hypertension is suspected, an ophthalmologist usually examines the optic nerve for swelling (papilledema). [aapos.org]

  Frisén papilledema grade is an ordinal scale that uses ocular fundus features to rate the severity of papilledema; grade 0 indicates no features of papilledema and grade 5 indicates severe papilledema. [clinicaltrials.gov]

• Intracranial Hemorrhage

  The system contains 8 features (risk factors) determining surgical prognosis: systemic illness, clinical-anatomical classification of intracranial hemorrhage, delayed cerebral ischemia (spasmogenic), intracranial hypertension, hydrocephalus, clinical [patentscope.wipo.int]

  […] as a tumor, hydrocephalus, intracranial hemorrhage, trauma, infection, or interference with the venous flow from the brain. [medical-dictionary.thefreedictionary.com]

  An MRI had been performed after delivery and was negative for intracranial hemorrhage, mass, or hydrocephalus). (eFigure 2. [fedprac.com]

  Likewise, an intracranial hemorrhage will result in a relative increase in the amount of blood in the cranial vault. [clinicaladvisor.com]

• Vertigo

  By Allison, United States, February 17, 2015 Three years ago I began to experience severe daily headaches, nausea and vertigo. [rarediseaseday.org]

  Several weeks before her visit, her headaches worsened and were accompanied by vertigo and visual disturbances. Seen in the emergency department with headache and reduced visual acuity, she was again given a diagnosis of chronic migraine. [acatoday.org]

• Hyporeflexia

  Macaya ARoing MFernrndez JMBoronat M Pseudotumor cerebri, spinal and radicular pain, and hyporeflexia: a clinical variant of the Guillain-Barré syndrome? Pediatr Neurol. 1988;4120- 121 Google Scholar Crossref 15. [jamanetwork.com]

  Health care providers should be esp. alert for signs of toxicity, e.g., an absence of patellar reflexes (hyporeflexia), flushing, and muscle flaccidity. [medical-dictionary.thefreedictionary.com]

To make the diagnosis of intracranial hypertension, various studies need to be conducted, but a preliminary suspicion can be made if a proper physical examination is conducted and if information regarding the onset and appearance of symptoms are obtained. History of trauma or malignant disease may significantly aid in making the diagnosis. Laboratory studies include CBC, serum electrolytes, albumin and arterial blood gasses. CT or MRI should be conducted immediately in the setting of head injury or suspicion of a CSF infection that can reveal the presence of a hematoma (either subdural or epidural) or an abscess. Measurement of ICP is often the mainstay in making the diagnosis and various techniques of measuring pressure exist, the gold standard being the ventriculostomy catheter. This techniques comprises insertion of a catheter through the skull and into the ventricular system [2]. Up 10 mmHg is considered to be normal, but values of 20 mmHg or more can cause significant nerve damage and severely impair perfusion of the brain [1]. Strict indications for ICP monitoring through this method exist, however, and include a glasgow comma (GCS) scale 3-8, hematoma, cerebral edema, herniation, systolic blood pressure of < 90 mmHg and age > 40 years [2]. The prognostic value of ICP measurement has shown the importance of its monitoring in the intensive care setting [11]. A lumbar puncture may be performed and opening pressure indirectly indicates the levels of ICP. Subsequent CSF analysis for protein, glucose and cellular content and can exclude CNS infection in the process. The diagnosis of idiopathic intracranial hypertension can be made after all other etiologies are excluded and diagnostic criteria include: Presence of typical symptoms, absence of focal neurological deficits (apart from sixth cranial nerve palsies), CSF pressure opening of more than 25 cm H20 (> 18 mmHg) on lumbar puncture together with absence of cytological and chemical findings and normal results on imaging studies [3].

The main goal of therapy is to maintain ICP at levels below 20-25 mmHg, achieve adequate cerebral perfusion and manage underlying conditions that provoke intracranial hypertension, if possible [2] [4]. The approach to treatment is complex and requires several modalities to achieve optimal outcomes. Firstly, facilitating proper venous outflow is vital by elevating the patient's head, while respiratory failure, if present, should be adequately handled using assisted ventilation and oxygen therapy [2]. Fever should be immediately reduced to physiological values, mainly through use of non-steroidal anti-inflammatory drugs (NSAIDs), as hyperpyrexia significantly may significantly increase ICP. Additional measures include management of systemic hypertension, as well as prophylactic use of anti-epileptics. The mainstay of therapy, however, is administration of hyperosmolar agents such as mannitol and cerebrospinal fluid evacuation in some cases. Mannitol induces expansion of plasma fluid volume within minutes after its administration and it is given in a bolus of 0.25-1 g/kg of body weight [2]. It is very effective, but higher doses may lead to significant hypotension, which is why close monitoring of patients is necessary when using this drug. Hypertonic saline solution is also recommended for use in such circumstances. CSF drainage is an invasive but very effective method of ICP reduction, but it cannot be used in all patients since ventricular collapse may develop in the setting of profuse edema [2]. If malignant tumors are the underlying cause, the use of steroids such as dexamethasone has shown benefit in reducing cerebral edema [2]. For patients with refractory intracranial hypertension, barbiturate-induced sedation may be considered, but the exact mechanism of therapy remains undisclosed. Several adverse effects, however, ave been reported, and including hypotension, respiratory complaints, hepatic and renal dysfunction, but also hypokalemia [2]. The last resort is decompressive craniectomy, which is used when all other modalities fail.

The prognosis significantly depends on the etiology of increased pressure, as intracranial hypertension may be mild or severe enough to be life-threatening for the patient. Hematomas and systemic illnesses may be appropriately treated with surgery and drugs, but malignant diseases and severe CNS infections usually have a poor prognosis.

Causes of intracranial hypertension are numerous and include [1] [7]:

• Intracranial diseases - Brain tumors (either primary or metastatic disease), cerebrovascular insults (ischemic stroke, intracerebral hemorrhage), trauma that leads to epidural or subdural hematomas, as well as cerebral contusions, but also infection of the CNS, such as encephalitis or meningoencephalitis.
• Extracranial events - Diseases that interfere with gas exchange and lead to airway obstruction and hypoventilation, drugs such as tetracycline, rofecoxib and various compounds used in treatment of acne vulgaris and fulminant liver failure have been described in literature [5] [8]. Hyperpyrexia, hypertension, seizures and post-operative development of hematomas and increased cerebral blood volume are also listed as potential etiologies [2].
• Idiopathic - a specific subtype of intracranial hypertension that is diagnosed in the setting of an unidentifiable cause.

Exact incidence and prevalence rates of intracranial hypertension are not known. On the other hand, idiopathic intracranial hypertension occurs in approximately 1 per 100,000 individuals in the general population, but female gender and obesity are shown to be significant risk factors for this type, as incidence rates in this sub-group rise up to 20 per 100,000 [9]. Nutritional factors, such as hypervitaminosis A, hypoparathyroidism, Addison's disease and steroid withdrawal are additional risk factors for idiopathic forms [10].

Normally, the intracranial pressure is constantly being regulated by changes in the CSF and blood content through various neurogenic and metabolic signaling pathways. ICP is one of the most important mediator of brain perfusion, together with arterial blood pressure. In the presence of various pathological conditions, this balance is disturbed. Tumors, abscess, hematomas, or even cysts can cause mechanical compression of the vasculature leads to pooling of fluid into the interstitum and edema, while a similar end-result is seen in hyperpyrexia, which induces cerebral vasodilation [2]. Conditions that disrupt normal gas exchange and produce hypercapnia consequently elevate ICP through the effects of carbon dioxide on the cardiovascular system. On the other hand, hypocapnia is shown to decrease blood flow [5]. In the setting of idiopathic intracranial hypertension, the pathophysiological mechanism remains unclear, but several compounds, including corticosteroids, vitamin A and aquaporin-1 channels have shown to be important mediators [10].

Having in mind the fact that this condition appears in a vast number of conditions and diseases of various origins and its occurrence is a result of very discrete disturbances that cannot be acted upon, preventive strategies currently do not exist.

Intracranial pressure is normally defined as the pressure exerted by contents of the endocranium on the dura and it may rise in a plethora of conditions [1], both neurological and non-neurological. Trauma (e.g. development of epidural and subdural hematomas), brain tumors, cerebrovascular diseases, systemic illnesses in which airway obstruction and impairment of gas exchange occurs, diseases that induce hyperpyrexia, seizures, infections of the central nervous system and certain drugs are potential etiologies [2]. Idiopathic intracranial hypertension (IIH) is a separate entity that is seen in young obese women and results in signs and symptoms of increased pressure without an identifiable cause [3]. Under physiological conditions, small quantities of cerebrospinal fluid (CSF) and blood, as well as physical presence of the brain, are key elements that define the values of intracranial pressure (ICP) that is vital for enabling adequate perfusion of the brain, together with mean systemic arterial pressure (MAP) [2]. In the setting of abscess formation or hematoma, their mechanical compression directly increases ICP, whereas changes in partial pressures of oxygen and carbon dioxide that may be seen in numerous systemic illnesses also induce ICP changes, as hypercapnia increases intracranial pressure and hypocapnia decreases cerebral blood flow [4]. Brain edema is one of the most common end-results of intracranial hypertension and stems from disruption of the blood-brain-barrier as well as impaired regulation of fluid and electrolytes [5], thus leading to fluid accumulation in the interstitial space, and consequently increasing ICP. The most common symptoms include headache, nausea, vomiting and altered consciousness that may range from mild to severe and coma is not uncommon [6]. Depending on the underlying etiology, accompanying signs may include fever (in the case of a CNS infection), bruising and injury of the head (seen in trauma), seizures, neurological deficits (often encountered in cerebrovascular diseases and brain tumors) and respiratory complaints. A thorough physical examination and a detailed patient history is the first step of the diagnostic workup and may reveal key findings in guiding the physician to the underlying cause. Laboratory studies including complete blood count (CBC), arterial blood gas analysis, serum electrolytes and protein levels should be obtained. Although it is not indicated in all patients, invasive ICP measurement can be an useful tool in making the diagnosis of intracranial hypertension and can be achieved through techniques such insertion of a ventriculostomy catheter. Normal ICP is around 10 mmHg and levels of 20 mmHg or more can severely affect the brain perfusion and produce permanent nerve damage [1]. For this reason, the condition should be taken seriously and treatment should be started immediately in the case of high clinical suspicion. Prior to ICP measurement, imaging studies such as computed tomography (CT) or magnetic resonance imaging (MRI) can point to the diagnosis, after which lumbar puncture can be performed and provide information regarding the content of the CSF that may be of significant value. Administration of mannitol, a hyperosmolar agent that provides plasma volume expansion and cerebrospinal fluid evacuation are the two most important treatment modalities in intracranial hypertension. Induced hypocapnia, neurosedation through barbiturate use [4], administration of corticosteroids and antipyretics, as well as surgery may be indicated, depending on the underlying disease and response to initial therapy.

Intracranial hypertension is a condition that arises as a complication of numerous diseases that exert pressure changes in the brain. Head injury that results in development of hematomas, brain tumors, infections of the central nervous system, cerebrovascular diseases (such as stroke) and numerous other conditions that provoke extreme hyperthermia, hypertension and lung failure can induce intracranial hypertension. A specific subtype called idiopathic intracranial hypertension (meaning that the cause is not found), is for unknown reasons most commonly diagnosed in obese women. Normally, the pressure inside the skull is maintained by the brain and small amounts of blood and cerebrospinal fluid and numerous factors have shown to influence its value, including body temperature and carbon dioxide. Intracranial hypertension may develop either due to physical presence of a mass (tumor, hematoma, abscess, cyst) or as a result of systemic circulatory changes that result in pooling of fluid into the intercellular space of the brain, thus creating brain edema (swelling). Consequently, symptoms such as headache, nausea and vomiting appear, while most patients develop some degree of altered consciousness. Unfortunately, many patients present with severely altered mental states and coma is often seen in those suffering from severe intracranial hypertension. To make the diagnosis, physical examination and patient history should be carried out properly, supported by laboratory and imaging studies. Blood count, serum electrolytes and proteins, as well as arterial blood gasses (oxygen and carbon dioxide) should be evaluated, but imaging studies such as computed tomography (CT scan) or magnetic resonance imaging (MRI) can reveal the presence of a mass or an underlying process in the brain that causes increased pressure. A lumbar puncture may be performed and a significantly elevated opening pressure can support the diagnosis. Measurement of intracranial pressure can be performed through insertion of a catheter through the skull, but strict indications exist for this highly invasive diagnostic method. Treatment of patients requires a multimodal approach, but the most important part of treatment is administration of mannitol, a drug that shifts fluid from the spaces surrounding brain into the blood vessels and effectively treats intracranial hypertension. Drainage of cerebrospinal fluid is also a potent therapeutic strategy, but it is more invasive and it cannot be used in all patients. Respiratory depression and fever should be treated using assisted ventilation, oxygen therapy and non-steroidal anti-inflammatory drugs (NSAIDs), respectively. In patients who do not respond to therapy, sedation by barbiturates is often indicated, while corticosteroid use in patients in whom a diagnosis of a brain tumor is made shows significantly better effects if used together with mannitol. The prognosis of intracranial hypertension solely depends on the underlying cause. Brain tumors and severe infections of the central nervous system carry a poor prognosis, whereas hematomas can be successfully treated with surgery. For these reasons, an early diagnosis and rapid therapy are important.

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