Neurofibroma: Genetic Traits and Impact Research Paper
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However, recently, anesthesiologists have suggest a low to mid thoracic epidural combined with adequate general anesthesia. This anesthetic technique will allow for adequate inter-operative monitoring. After the operation, the anesthesiologist must continue to monitor the patient for either hypertension, hypotension and hypoglycemia. The presence of either of these conditions may alter the course of the medication given to the patient once the patient is removed from the anesthesia.
Neurofibroma can cause systemic problems within the various components of the Respiratory System. As has already been presented, Neurofibromas can cause partial blockages within upper parts of the trachea. However, Neurofibromas can also pose challenges or the anesthesiologist when dealing with nasal, sinus or maxilofacial cavities with Neurofibromas present within. One example of how devastatingly complex the Neurofibroma can become is seen when a benign neurofibroma can cause a superior vena cava compression. Such was the case of a 21-year-old female patient as reported by Oakley25. The patient was experiencing shortness of breath while at rest. Additionally, the patient had a family history of Neurofibroma in her family. After several chest x-rays a biopsy determined the mass was indeed caused by a neurofibroma. The tumor was excised and post-operative examination revealed the tumor was hyper-cellular suggesting a neurofibroma in growth stage without any malignant indications.
These types of tumors are difficult to treat under any conditions. The anesthetic considerations for these types of tumors are involved and complex. According to Dodge26 some patients may experience difficulty during an awake intubation, as a result these patients may undergo rapid induction and muscle paralysis after preoxygenation. This allows for several minutes of apnea without hypoxia during this time extracorporeal oxygenation could be introduced into the patient.
Another form of tumor present in the respiratory system in relation to NF-1 are Intrapulmonary Neurofibromas- these tumors are rare and carry a good prognosis 27. Recent surveys have indicated that this defect may result in pulmonary hypertension and right Ventricular failure. These conditions render an anesthesiologist's job increasingly difficult when monitoring a patient's blood pressure and pre-operative oxygen levels.
Chest Wall Deformities
Chest Wall deformities are often the result of severe aberrations of the spinal column usually as a result of severe scolosis. This condition is common in NF-1 patients and impacts approximately 10% of NF-1 patients. Typically this affliction occurs in young children with corrective surgery being the mode of treatment 28. A significant form of scoliosis- kypho-scoliosis, is uncommon, however it has been found to be associated with tumors and a higher than normal neurological deficit- two hallmarks of Neurofibroma 29. Kypho-scoliosis may lead to rotation and as a result could cause a reduction in lung volume and breathing capacity. This scoliosis may ultimately lead to respiratory failure 30. Neurofibroma may lead to a gradual degradation of the rib cage and produce a condition known as "flial chest"; however research has shown this cause to be more uncommon than not.
Hypertension is normally associated with the Cardiovascular system as it relates to diet and cholesterol levels. However Neurofibroma may impact hypertension. Approximately 6% of patients with Neurofibroma are hypertensive. However, in 30% of patients, the symptom is the result of a secondary condition much like a renovascular disorder. Those younger patients who have been diagnosed with Neurofibroma are most likely suffering from a disease called Renal Artery Stenosis. Surgery from this disease has been shown to offer mixed results; however a form of angioplasty, precutaneuos angioplasty has been found to alleviate hypertension.
A more common disorder associated with Hypertension and Neurofibroma is Phaeochromocytoma. These tumors affect 0.1% to 7.5% of patients with NF-1, however 25% of patients diagnosed with Phaeochromocytoma have NF-1-31. Patients exhibiting these tumors tend to be older-mean age 45 and the tumors tend to be non-malignant. There are several common symptoms. They include sudden and sharp frontal or occipital lobe headaches, weight loss and palpitations- these symptoms occur in approximately 60% of all Neurofibroma patients 32.
The anesthetic considerations for this disorder are numerous and complex. The preoperative considerations include evaluating the patients blood pressure and heart rate change. These two factors could be evidence of myocardial schemia. Also, the anesthesiologist must account for an adrenergic blockade. The most critical anesthetic considerations occur in the operating room. During the procedure the anesthesiologist must evaluate the arterial line, monitor urinary output, intubate deep and monitor any inter-operative hypertension. If such hypertension occurs during surgery it can be treated
with phentolamine, nitroprussside or nicardipine. Post-operative considerations involve continued monitoring of hypertension which could indicate additional tumors.
Neurofibroma may lead to the formation of aortic and cerebral aneurysms 33. It has been proposed that these structures are the result of Schwan cell proliferation with a secondary fibrosis forming on the vessel wall. Although some studies show congenital heart failure as the leading cause34, a secondary review showed no clear evidentiary support 35. The presence of these aneurysms may represent a vascular manifestation of a Neurofibroma. Related to the advent of aortic aneurysms is the onset of hypertrophic cardiomyopathy in relation to Neurofibroma36.
The appearance of such myopathy in conjunction with Neurofibroma has been questioned. Recent studies have demonstrated that Neurofibroma is possibly a secondary cause of this myopathy in that both Neurofibroma and hypertrophic cardiomyopathy involve an abnormal metabolic rate and both represent defects in the development of neural tissue. Furthermore, Neurofiborma may cause the heart to develop hypertrophy and outflow obstruction.
Vascular inflammation results from deficiencies in Neurofibronin. NF1 patients display diverse clinical manifestations, including vascular disease, which results from neointima formation and vessel occlusion. Vessel wall homeostasis is maintained by complex interactions between vascular and bone marrow -- derived cells (BMDCs), and neurofibromin regulates the function of each cell type. analysis of peripheral blood from NF1 patients without overt vascular disease revealed increased concentrations of inflammatory cells and cytokines previously linked to vascular inflammation and vasoocclusive disease37
Central Nervous System
Tumors within the Central Nervous System contribute to the overwhelming percentage of the mortality rates among patients with Neurofibroma. Therefore it is logical to conclude these patients needing cranial or spinal neurosurgery. The anesthetic considerations for this type of surgery are along the lines as normal neural surgery.
Prior to surgery the Anesthesiologist must consider the enhance probability of epilepsy, cognitive impairment and the likelihood of undiagnosed Central Nervous System tumors. Cerebrovascular Disease has been reported and presents the similar pathology as Vascular Neurofibromas. However this manifestation is relatively uncommon.
Neurofibroma also plays a significant role in impacting cognitive functions38. Neurofibroma controls the expression of ERK signaling in GABA release 39. The disruptions caused by the mutations resulting Neurofibroma-1, lead to a disruption in the mechanisms that govern learning. Therefore, Neurofibrin regulates, ERK and Synapsis I which in turn affects GABA release and impacts long-term potentiation.
Neurofibromatosis-1 can be used to ascertain the cause of low-grade gliomas in children. Through using NF-1 mice models, researchers have been able to develop models that allow researchers to locate critical growth pathways, define the contribution of the tumor micro-environment to glioma growth and assisted in developing and understanding of the basis for glioma growth. Furthermore such mice models have been used to develop the therapeutic studies to evaluate the efficacy and safety of pharmacological treatments for juvenile gliomas40. It is important to use small-animal models to determine why certain therapies might fail. In addition to the reasons outlined above, defining tumor escape mechanisms (eg, feedback loops, activation of other signaling pathways) are critical to the design of future anticancer drugs.
Gastrointestinal tumours in NF1 may present with disordered gut motility, abdominal pain, haematemesis or melaena; although neurofibromas, usually affecting the jejenum or stomach, are the most common lesions, leiomyoma, ganglioneuroma and sarcoma have been described. All may result in intestinal perforation. Gastrointestinal symptoms may be the first manifestation of neurofibromatosis.
Gastrointestinal abnormalities in patients with NF-1 are reported to occur in up to 10~25% of patients and consist of four groups of lesions: mesenchymal neoplasms; hyperplasias of intestinal neural tissue; neuroendocrine tumors of the duodenum; and rarely, other gastrointestinal neoplasms such as adenocarcinomas41. Although neurofibromas are the most commonly encountered mesenchymal neoplasm of the gastrointestinal tract in patients with NF-1, Gastrointestinal stromal tumors (GISTs), leiomyomas, and leiomyosarcomas also occur
Clinical symptoms are related to the size and location of the GISTs. Most pathologists use a combination of tumor size and mitotic rate to assess the malignant potential of these tumors. In general, malignant GISTs are larger, more cellular, and more mitotically active. GISTs that are smaller than 5 cm with five mitoses per 50 consecutive high-power fields or less are considered to be benign with a low risk for metastasis. Tumors larger than 10 cm with more than five mitoses per 50 high-power fields are considered to be malignant. All tumors falling between these two extremes are considered to be of uncertain malignant potential with intermediate risk for metastasis. Tumors with more than 50 mitoses per 50 high-power…
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