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Physiological Nature of Anaplastic Astrocytoma

Anaplastic astrocytoma (AA) is an astrocytic glioma which is characterized by high infiltration and shows increased cellularity. Other characteristic features of the WHO grade III glioma is pronounced mitotic activity as well as cytologic atypia. The composition of anaplastic astrocytoma among all astrocytic gliomas is roughly 10-25 percent and peak years for the condition are between 40 and 45 years (Tonn et al., 2006). The anaplastic astrocytoma is a tumor that develops in the brain whereby the nerve supportive cell (astrocytes) develops the glioma. These brain tumors have the capacity to invade peripheral cells and therefore they have a potential to affect the brain hemispheres (white matter) adversely. Being high –grade gliomas, the anaplastic astrocytoma are said to develop from the low-grade gliomas and they differentiate over a given period of time (usually an interval of between less than one year to more than 10 years) to become the anaplastic astrocytoma (Drevelegas, 2010). Due to their diffusive nature, anaplastic astrocytomas tend to recur more frequently and their surgical removal is often difficult. Moreover, surgery is accompanied by the risk of causing disability, depending on the location of the tumor in the brain. Some of the affected areas of the brain are areas that control speech, vision and motor actions and therefore anaplastic astrocytoma can be accompanied by mental problems (Bradle, 2004).
From the presentation of anaplastic astrocytoma and its accompanying symptoms such as seizures and epilepsy, the patient often undergoes a life altering experience that may leave the individual devastated. This paper discusses the structural and functional changes that come with anaplastic astrocytoma. Moreover, personality and mental problems that accompany the condition are incorporated in this paper. The diagnostic and therapeutic steps that can be taken to address anaplastic astrocytoma as well as the prognosis of the condition are also discussed in this paper.
Development and Presentation of Anaplastic Astrocytoma
            The WHO III tumors, anaplastic astrocytomas, are known to appear in a later age compared to low-grade astrocytomas, with the incidence peaking during the 40s and 50s. In a retrospective study involving 383 AA patients, Afra et al. (1999) identified the mean age for AA patients as 40.6 years. Anaplastic astrocytoma is more common in males than in females with Afra et al. (1999) reporting a male to female ratio of 106: 82 in a retrospective study involving 383 anaplastic astrocytomas. Tonn and colleagues (2006) describe that AA are primarily found in the cerebral hemispheres. It is identified that most AAs are located both in the frontal and temporal lobes. However, it is also possible to find anaplastic astrocytomas on the brain stem as well as the thalamus of young adults and children. Perifocal edema is seen to accompany the expanding lesions that represent anaplastic astrocytomas. It has also been reported that frontal lobe has the highest incidences of astrocytomas (about 46%) followed by the temporal lobe which makes roughly 31 percent of brain tumors while parietal tumors are the least, composing about 15 percent of the astrocytomas.
A histopathological presentation of AA indicates either focal or diffuse anaplasia as well as increased cell formation with no nucleus. The mitotic activity is often pronounced and tendency of the tumors progressing to secondary globiastoma is usually very high, with no necrosis or microvascular proliferation (Tonn et al., 2006). Anaplastic astrocytoma may contain violations in the cerebral lobes or contralateral hemisphere. The tumor often appears as gray red and has a soft texture and appears to invade surrounding tissues.
Anaplastic astrocytomas usually present with the symptom of an epileptic seizure. This symptom is also highly relied upon as an indicator of onset of astrocytomas with Afra et al. (1999) reporting epileptic seizures in 48% of all the 383 AA patients. In most cases, epileptic seizures may date up to 17 years with most cases occurring for a period of 3 years and rarely for more than 10 years. Patients who have a relatively long duration of epileptic seizures have low number of fits, which are short-lived focal and/ or temporal fits and consciousness is hardly lost. Persistence of seizures for a very long period is said to be an indicator of progression of low-grade tumors to high-grade tumors (AA).
There are various behavioral characteristics that are encountered as symptoms of anaplastic astrocytomas, both in the developmental and progression stages. Cutts et al. (2002) report recurrent goosebumps attacks in a 49-year-old man and the attacks would be felt in form of tingling of the whole body and piloerection of the whole body, which are defined as pilomotor seizures. The pilomotor seizures were followed by impaired memory and insomnia followed due to more frequent (usually more than once daily) pilomotor seizures. Other characteristics that followed pilomotor seizures, as reported by Cutts et al. (2002), included fatigue, metallic taste aura as well as losing sense of time. The patient also presented with numbness in the head and continued loss of memory. These were characteristic features of anaplastic astrocytoma as confirmed by biopsies that showed a tumor in the fronto-parietal region with diffusion into the right temporal lobe. The size of the tumor continued to increase with time and memory loss was still persistent. It was therefore confirmed that AA affects the temporal lobes and usually invades the periventricular nuclei of the hypothalamus leading to abnormal piloerection (thermodysregulation).
While epilepsy presents in approximately 50 percent of the cases during onset, other symptoms have been demonstrated in most patients. These include headache, visual changes, dysphagia, psychiatric symptoms, somnolence, weakness of the limbs and vomiting. Health Writings (2008) demonstrated hemiplagia in 59 percent of study subjects, 47 percent of optic disc edema cases and 46 percent of cases with impaired brain performance. In some cases, about 32 percent, it was identified that sensory loss occurred on one side of the body. Over time, certain symptoms become worse and these included intracranial pressure, nervous weakness, epilepsy as well as loss of memory and confusion. These are adverse presentations of AA as a result of brain damage by the invasive tumor.
Diagnosis and Treatment
Treatment of anaplastic astrocytoma takes different modes including radiotherapy, surgery and chemotherapy. Prior to the advent of computerized tomography (CT) and the magnetic resonance imaging (MRI), angiography was the commonest diagnostic procedure for anaplastic astrocytoma. Angiography was poor in detecting tumors at an early age and epilepsy attacks would be used as a predictor symptom AA (Afra et al., 1999). Afra and colleagues argue that it would require repeat angiography to indentify the tumor which would have developed to an acknowledgeable size and then treatment/surgery would follow. Since the timing of surgery from the first time seizures are detected is important in determining the survival rate, the ability to detect the AA at an early age is crucial. Afra et al. (1999) mention that the longer the history of seizures, the higher the likelihood of presence of malignant transformations and the lower the survival rates. This is an implication that the timeliness of diagnosis and treatment of AA affects the behavioral presentation caused by the tumors with seizures being more prevalent in untreated tumors. In fact removing the tumor at an early age has the potential to prevent recurrence and even the progression grade II to grade III tumors to some degree.
Prognosis and Recurrence
The prognosis of anaplastic astrocytoma is poor regardless of the treatment option, hence cases of recurrence are very common (Health Writings, 2008). The survival rate of AA patients is usually three years in average since the tumors exhibit a poor prognosis. Bradley (2004) mentions that the survival rates vary significantly from individual to individual with the age of the individual being a crucial determinant of survival rate. As such, younger patients have a remarkably higher survival rates compared to old patients. The characteristic symptoms of AA are seizures and deficits in focal functioning. The prognosis of AA is observed to be poor and highly determined by several factors including age of the patient, location of the tumor, Karnofsky performance status (KPS), Ki67 labeling index, and amount of radiation among other factors (Nomiya et al., 2008). The radiation dose that is most appropriate for AA is 72 Gy as it results into tolerable toxicity. Brain necrosis is reported to be a common occurrence if excessive irradiation is administered together with a high dose of chemotherapy. This may affect brain function and behavior with most cases resulting to reduced survival rates.
Recurrence accompanied by malignant progression is a characteristic of anaplastic astrocytoma as indicated by Sarkar et al. (2002). Among 10 cases of anaplastic astrocytoma that were studied by these authors to identify the recurrence rate as well as malignant progression of the tumor among other astrocytomas, it was identified that 64% of the AA cases recurred with malignant progression, which was associated with presence of p53 protein. The recurrence range of AA was identified to be between 6 and 30 months. Usually, the malignant progression that recurs in AA cases is the development of the glioblastomas. This is an indication that AA patients who experience recurrence often experience more severe symptoms due to the malignancy nature of the recurred tumors as well as their progression to glioblastomas.
Anaplastic astrocytoma is a brain tumor that presents during mid-life, specifically during the fourth and fifth decades of life. These highly diffusive tumors affect the lobes of the brain with the frontal lobe and the parietal lobes being key targets. As a result of this, the functions of brain performed by these hemispheres are highly affected and they present as altered behaviors which form the symptoms of anaplastic astrocytoma. It is therefore identified that seizures, more so epileptic seizures, are the initial symptoms of anaplastic tumors. Pilomotor seizures, impaired memory, visual distortions, headache, somnolence, confusion and weak limbs are also behavioral patterns that predict anaplastic astrocytoma and they signify impaired functioning of frontal and parietal lobes. Anaplastic astrocytoma can be diagnosed using CT and MRI among other techniques but angiography is poor in detecting AA in initial stages. While AA can be treated through surgery, radiotherapy or chemotherapy, the diffusive nature of the tumors inhibit complete cure. As such, prognosis is poor and recurrence of the tumors, with malignancy in most cases, is common making the survival rate be as short as three years. Recurrence implies that the symptoms of AA also recur and malignancy as well as progression to glioblastomas is often exhibited. Brain damage is therefore extensive and brain function and behaviors controlled by the affected brain parts are severely affected.

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