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Glioblastoma Multiforme

Glioblastoma is considered to be the most severe form of astrocytomas and carries a very poor prognosis. Increased intracranial pressure leading to headaches, ataxia, visual deficits, and various other neurological deficits are encountered. Imaging studies are mandatory in order to make the diagnosis, whereas biopsy and subsequent histopathological examination, often performed postoperatively, confirms the type of the tumor.

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Presentation

Glioblastoma (also known as glioblastoma multiforme, or GBM), is most frequently diagnosed among the elderly, with a median age of diagnosis being 64 years and a significant predilection toward male gender [1] [2]. However, pediatric cases have also been documented, in whom an even stronger male predilection exists [1]. Although glioblastomas are not that common (incidence rate is about 2-5 per 100,000 individuals), they carry a very poor prognosis [1] [2]. Overall survival rarely exceeds 12-14 months from the time of diagnosis, which is why, according to the World Health Organization criteria (WHO), it is classified as a stage IV astrocytoma [3] [4] [5]. One of the reasons why such a poor outcome is expected is that GBM is often missed in its initial stages due to a nonspecific symptomatology and physicians often turn their attention to infections, vascular processes or immunological diseases prior to suspecting neoplastic disorders [1]. The clinical presentation initially includes headaches (due to increased intracranial pressure caused by the tumor), vomiting, nausea, frequent syncope and seizures, which may be the only sign in patients without a previous history of epilepsy [1] [6]. In time, cognitive dysfunction can appear, as well as gait disturbances, cranial nerve palsies, urinary incontinence, hemiparesis, aphasia, and disorientation, while vertigo is described in a minority of cases [1] [2] [6]. Moreover, various psychiatric manifestations have been described in patients with glioblastomas, such as personality disorders, loss of emotional control and anger, mood disorders (depression, mania) and marked anxiety, whereas hallucinations and psychosis, although rare, have also been observed [7].

Weakness
  • We compared characteristics between weak and strong galectin-1 expression, and only the expression level of galectin-3 showed a correlation.[ncbi.nlm.nih.gov]
Sputum
  • Predicting lung cancer by detecting aberrant promoter methylation in sputum. Cancer Res 2000 ;60: 5954 - 5958 18. Gorlia T, Stupp R, Eisenhauer EA, et al.[doi.org]
Vomiting
  • Main presenting symptoms included headache (85%), nausea or vomiting (65%), and seizures (35%). Papilledema (45%) was the most common physical finding. The longest survivals were achieved by a combination of operation and radiation (22 months).[ncbi.nlm.nih.gov]
Nausea
  • Main presenting symptoms included headache (85%), nausea or vomiting (65%), and seizures (35%). Papilledema (45%) was the most common physical finding. The longest survivals were achieved by a combination of operation and radiation (22 months).[ncbi.nlm.nih.gov]
  • The clinical presentation initially includes headaches (due to increased intracranial pressure caused by the tumor), vomiting, nausea, frequent syncope and seizures, which may be the only sign in patients without a previous history of epilepsy.[symptoma.com]
Persistent Vomiting
  • Herein, we present a case of intraventricular glioblastoma multiforme (GBM) in a 16-year-old child with L2-HGA who presented with rapid functional decline and persistent vomiting.[ncbi.nlm.nih.gov]
Diplopia
  • Case 2: Meningeal involvement A 31-year-old man presented with seizures and subsequent diplopia. Initial imaging revealed a space-occupying, non-enhancing lesion in the optic chiasm. An excision biopsy showed a grade II astrocytoma.[sajr.org.za]
  • […] patients with supratentorial brain tumors. [2] o Increased Intracranial Pressure o Headache, especially retroorbital; sometimes worse upon awakening, improves during the day o Vomiting (with or without nausea) o Visual changes (blurring, blind spots, diplopia[physio-pedia.com]
  • Patients usually report positional headache (worse in a dependent position), visual obscurations, exacerbation of focal symptoms, or sudden aggravation of seizures possibly followed by lethargy, nausea, vomiting, and diplopia 18, 52.[doi.org]
Visual Impairment
  • Treatment is given to relieve the symptoms, particularly visual impairment. Treatment may include repeated lumbar punctures or medications to decrease CSF. In severe cases, a shunt may be needed.[braintumor.org]
Enlarged Blind Spot
  • A 21-year-old man, who had GBM 7 years ago complained of a transient shadow in his vision and presented with normal visual acuity but optic disc edema and an enlarged blind spot in the right eye (oculus dexter, OD).[ncbi.nlm.nih.gov]
Muscle Weakness
  • Brain cancer symptoms Common symptoms of brain cancer may include headache, blurred or double vision, hearing loss, nausea or vomiting, memory loss, seizures, muscle weakness, speech difficulty, mood changes, unexplained tiredness, changes in menstrual[cancercenter.com]
  • Common symptoms patients with glioblastoma experience include headaches, seizures, confusion, memory loss, muscle weakness, visual changes, language deficit, and cognitive changes.[rarediseases.org]
Seizure
  • A 55-year-old woman with a history of celiac disease presented with focal seizures and a mass lesion located at the left frontal lobe. Management of seizures in these patients is challenging.[ncbi.nlm.nih.gov]
  • Seizures The type of seizures depend on where in the brain the tumor is located.[everydayhealth.com]
Headache
  • Main presenting symptoms included headache (85%), nausea or vomiting (65%), and seizures (35%). Papilledema (45%) was the most common physical finding. The longest survivals were achieved by a combination of operation and radiation (22 months).[ncbi.nlm.nih.gov]
  • : Different From Other Headaches Headaches occur in about 50 percent of glioblastoma patients.[everydayhealth.com]
  • Increased intracranial pressure leading to headaches, ataxia, visual deficits, and various other neurological deficits are encountered.[symptoma.com]
Personality Change
  • General symptoms for metastatic brain tumors include: Headaches Weakness on one side of the body Problems with balance Seizures Behavior, memory and personality changes Glioblastoma Mulitiforme Treatment Treatment plans are dependent upon the numbers[uwhealth.org]
  • changes Behavioral changes, development of inappropriate behaviors Memory loss Diagnosis Images and scans may be taken of your brain with: CT scan MRI scan Functional MRI (fMRI) Positron emission tomography (PET) scan Your brain activity may be measured[neurosciences.uvahealth.com]
Aphasia
  • A 42-year-old man visited our clinic because of right hemiparesis and total aphasia. Head magnetic resonance imaging demonstrated enhanced multiple cystic lesions in the left temporal lobe suggesting an intra-parenchymal brain tumor.[ncbi.nlm.nih.gov]
  • Case report A 58-year-old woman was admitted to the emergency room with acute onset of global aphasia.[em-consulte.com]
  • In time, cognitive dysfunction can appear, as well as gait disturbances, cranial nerve palsies, urinary incontinence, hemiparesis, aphasia, and disorientation, while vertigo is described in a minority of cases.[symptoma.com]
  • His development of expressive aphasia and mood disturbances over a relatively brief time period are all worrisome for central nervous system neoplasia.[oncolink.org]
  • Five months later, he had an episode of confusion with receptive and expressive aphasia, lasting a few minutes, but no associated seizure.[sajr.org.za]
Dizziness
  • A 42-year-old woman was referred to our hospital for occipital constrictive headache, dizziness and gait disturbance. Multimodality imaging including computed tomography and magnetic resonance imaging (MRI) showed a right cerebellar mass.[ncbi.nlm.nih.gov]
  • Proteinuria and edema Cardiac impairment Vascular system Thrombotic events Bleeding and disturbed wound healing Blood values Leukopenia and changes in hemoglobin levels Lymphopenia and immmunomodulation Hypothyroidism and other endocrine dysfunctions CNS Dizziness[medscape.com]
  • Constantly dizzy, unable to do much at all really. But yes you are right, like your husband, he is not the same man and that is heartbreaking for myself and our 10 yr old son.[cancerresearchuk.org]
  • Significant symptoms included intermittent vomiting, intermittent constipation, dizziness, headaches, numbness of the left arm, stiffness of both arms, and a pressure feeling of the posterior neck.[medicorcancer.com]
  • […] sleepiness, unconsciousness, and coma) Changes in hearing, taste, or smell Changes that affect touch and the ability to feel pain, pressure, different temperatures, or other stimuli Confusion or memory loss Difficulty swallowing Difficulty writing or reading Dizziness[mountsinai.org]

Workup

A complete physical workup is essential in order to place glioblastoma into the differential diagnosis of nonspecific central nervous system (CNS) symptoms and associated features. Firstly, a detailed patient history can reveal a history of epilepsy, the appropriate age for the development of glioblastoma (elderly patients) and a somewhat sudden onset of symptoms. Secondly, a thorough physical examination confirms the presence of neurological deficits and roughly determines the area of the brain that is affected by the underlying disorder. To solidify the diagnosis, imaging studies are the modality of choice, ranging from computed tomography (CT) and magnetic resonance imaging (MRI) to more advanced methods, such as positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) [2]. MRI, and even CT, however, are often sufficient to confirm the tumor, and the mean diameter at the time of diagnosis is about 4 cm [1]. An enhancing heterogeneous mass with areas of central necrosis and surrounding edema is the typical presentation [2]. Despite evident clinical and imaging criteria, a definite diagnosis can only be made after obtaining a valid sample for biopsy and a histopathological examination with immunohistochemistry [1] [2]. Postoperative sampling is mandatory, while in cases when the tumor is not resectable, a fine needle aspiration or stereotactic biopsy can be performed [1] [2]. The decreased presence of glial fibrillary acidic protein (GFAP) in glioma cells, as well as S100 positivity on immunohistochemistry, is important in the diagnosis of glioblastoma [1].

Treatment

  • The role of bevacizumab in the treatment of GBM continues to be a topic of ongoing research and debate. Despite aggressive treatment, these tumors remain undoubtedly fatal, especially in the elderly.[ncbi.nlm.nih.gov]
  • Nonsurgical treatment of recurrent glioblastoma Abstract Standard treatment for glioblastoma multiforme is surgery followed by radiotherapy and chemotherapy, generally with temozolomide. However, disease recurs in almost all patients.[doi.org]
  • In patients who responded to the treatments, Dr.[cancer.gov]

Prognosis

  • Prognosis Prognosis is poor, especially in the absence of gross total resection, in older patients and in case of severe neurological deficits. The documents contained in this web site are presented for information purposes only.[orpha.net]
  • Although therapeutic options have been improving, the prognosis of the primary spinal GBM remains poor.[ncbi.nlm.nih.gov]

Etiology

  • Furthermore, studies suggested that VEGF has the etiology in CSDH development, although its involvement is not fully understood.[ncbi.nlm.nih.gov]
  • Etiology The cause of the disease is unknown, except when it occurs after therapeutic irradiation of the brain for another disease.[orpha.net]
  • Fisher’s laboratory focuses on understanding the molecular and biochemical basis of cancer etiology and progression with an emphasis on translating this information to develop improved methods for diagnosing, staging and treating cancer.[nfcr.org]

Epidemiology

  • Several epidemiological studies have demonstrated the chemopreventive role of natural, dietary compounds in the development and progression of cancer.[ncbi.nlm.nih.gov]
  • Kozak KR, Moody JS: Giant cell glioblastoma: a glioblastoma subtype with distinct epidemiology and superior prognosis. Neuro Oncol 2009;11:833–841.[doi.org]
  • Summary Epidemiology Glioblastomas represent the most frequent brain tumors in adults, with an annual incidence of around 1/33,330. Prevalence is estimated at 1/100,000.[orpha.net]
Sex distribution
Age distribution

Pathophysiology

  • Paraskev Stoyanov", Marin Drinov 55 Street, 9002, Varna, Bulgaria. georgi.geesh@gmail.com. 2 Department of Physiology and Pathophysiology, Division of Pathophysiology, Faculty of Medicine, Medical University - Varna "Prof. Dr.[ncbi.nlm.nih.gov]
  • RO Weller , I Galea , RO Carare , etal: Pathophysiology of the lymphatic drainage of the central nervous system: Implications for pathogenesis and therapy of multiple sclerosis Pathophysiology 17: 295 – 306 , 2010 Crossref , Medline , Google Scholar 25[jco.ascopubs.org]

Prevention

References

Article

  1. Urbańska K, Sokołowska J, Szmidt M, Sysa P. Glioblastoma multiforme – an overview. Contemporary Oncology. Contemp Oncol (Pozn). 2014;18(5):307-312.
  2. Mesti T, Ocvirk J. Malignant gliomas: old and new systemic treatment approaches. Radiol Oncol. 2016;50(2):129-138.
  3. Louis DN, Ohgaki H, Wiestler OD, et al. The 2007 WHO Classification of Tumours of the Central Nervous System. Acta Neuropathologica. 2007;114(2):97-109.
  4. Aster, JC, Abbas, AK, Robbins, SL, Kumar, V. Robbins basic pathology. Ninth edition. Philadelphia, PA: Elsevier Saunders; 2013.
  5. Porter RS, Kaplan JL. Merck Manual of Diagnosis and Therapy. 19th Edition. Merck Sharp & Dohme Corp. Whitehouse Station, N.J; 2011.
  6. Sanli AM, Turkoglu E, Dolgun H, Sekerci Z. Unusual manifestations of primary Glioblastoma Multiforme: A report of three cases. Surg Neurol Int. 2010;1:87.
  7. Boele FW, Rooney AG, Grant R, Klein M. Psychiatric symptoms in glioma patients: from diagnosis to management. Neuropsychiatric Disease and Treatment. 2015;11:1413-1420.

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Last updated: 2019-07-11 20:45