My professor at Harvard Medical School Dr. Napadow has recently published a research on Monitoring acupuncture effects on human brain by fMRI. This confirms beyond any doubt the positive effect of Acupuncture on human brain for pain management. Here is the abstract:

Functional MRI is used to study the effects of acupuncture on the BOLD response and the functional connectivity of the human brain. Results demonstrate that acupuncture mobilizes a limbic-paralimbic-neocortical network and its anti-correlated sensorimotor/paralimbic network at multiple levels of the brain and that the hemodynamic response is influenced by the psychophysical response. Physiological monitoring may be performed to explore the peripheral response of the autonomic nerve function. This video describes the studies performed at LI4 (hegu), ST36 (zusanli) and LV3 (taichong), classical acupoints that are commonly used for modulatory and pain-reducing actions. Some issues that require attention in the applications of fMRI to acupuncture investigation are noted.

Authors: Hui KK, Napadow V, Liu J, Li M, Marina O, Nixon EE, Claunch JD, LaCount L, Sporko T, Kwong KK

PMID: 20379133 [PubMed]

Functional MRI evidence that acupuncture modulates the limbic system and subcortical gray structures of the human brain

Hui, Kathleen K.S,1,4; Liu, Jing4; Makris, Nikos2; Gollub, Randy L.1,3; Chen, Anthony J.W.1; Moore, Christopher I.1; Kennedy, David N.2; Rosen, Bruce R.1; Kwong, Kenneth K.1

1MGH-NMR Center, Department of Radiology,
2Center for Morphometric Analysis, Department of Neurology ,
3Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA,,
4 East-West Immune Institute, Lexington, MA

Introduction: Acupuncture has effects on multiple physiological systems. It is a promising complementary therapy for affective and psychosomatic disorders such as anxiety, depression, substance abuse, pain and visceral dysfunctions. We used fMRI to monitor its action on normal human brain, with the focus on the limbic system and subcortical gray structures that are intimately involved in the regulation of emotions, autonomic and endocrine functions. We demonstrated prominent and coordinated effects in these neural circuits. The pattern of response observed with acupuncture sensation was distinctly different from that observed with tactile stimulation or with pain sensation1. Follow-up study confirms reported findings and reveals involvement of additional brain regions that are closely related to the limbic system.

Method: Scanning was performed on 13 normal human volunteers in a 1.5Tesla GE Signa MRI System equipped for echo planar imaging. Ten coronal brain slices, each 6.5 mm thick with 0.5 mm gap, were used to cover the regions of interest. High-resolution structural maps were acquired by T1 weighted echo-planar recovery sequence for preliminary statistical mapping. A sagittal localizer scan with 60 slices was acquired by T1 weighted spoiled echo-gradient sequence for Talairach transformation. Functional MRI images were acquired by gradient echo T2-weighted sequence with TE 50 msec, TR 4.8 sec. Kolmogrov-Smirnov statistical images were reconstructed from individual and averaged data

Acupuncture was performed at LI. 4. The subjects received acupuncture stimulation twice, each lasting 2 minutes. The needle was twirled gently 120 times per minute using a balanced tonifying and reducing technique. The periods with needle in place (2 min before, 4 min between, 2 min after needle manipulations) served as baseline. Tactile stimulation using a matched paradigm was delivered over the acupoint for comparison with acupuncture data. Subjective sensations were recorded after each stimulation procedure.

Results: Signal increases occurred in the primary and secondary somatosensory cortices both in acupuncture and in tactile stimulation. A marked contrast was observed in the deep structures. The 11 subjects who experienced deqi demonstrated prominent decreases of fMRI signals in limbic and subcortical regions as the amygdala, hippocampus, parahippocampus, hypothalamus, septal nucleus, caudate, putamen, nucleus accumbens, anterior cingulate gyrus, anterior insula, temporal pole and fronto-orbital cortex The 2 subjects who had painful sensation during acupuncture demonstrated signal increases in these regions instead. Tactile stimulation group data did not elicit significant signal changes in the deep gray structures.

Whole brain imaging was performed on one subject with deqi and one subject with pain response more than 1 year later. Acupuncture evoked deqi in both subjects. The former demonstrated signal decreases in the limbic and subcortical gray structures as before. The latter showed a reverse in the direction of signal changes, from signal increases with pain before to signal decreases with deqi in the repeat study. Whole brain imaging revealed prominent signal decreases with deqi sensation in additional brain regions that are closely linked to the limbic system, such as the frontal pole, prefrontal cortex and cerebellar vermis.

Conclusion: The study provides evidence that supports a coordinated effect of acupuncture on a network of cortical and subcortical limbic and paralimbic structures including the frontal pole, the prefrontal cortex and cerebellar regions that are connected to the limbic system. in the human brain. Modulation of this neuronal network could initiate a sequence of effects by which acupuncture regulates multisystem functions. The effects on the limbic system could well contribute to its efficacy for the treatment of diverse affective and psychosomatic disorders.

Reference: Hui, K K.S. et al: Human Brain Mapping 2000, 9(1):13-25.

Neural bases of acupuncture: Observation of target specific and target non-specific acupuncture mechanisms observed by fMRI

Zang-Hee Cho, Radiological Sciences & Neuropsychiatry and Human Behavior, University of California, Irvine, CA

Functional Magnetic Resonance Imaging (fMRI) of the brain, using a variety of acquisition techniques, has been successfully applied to the study of large number of questions in human neuroscience. The success of the method has been due to its inherent
flexibility and non-invasiveness. The fMRI technique allows us to visualize many classes of functional behavior in the brain by detecting changes in blood oxygenation and related regional cerebral blood flow (rCBF) with high temporal resolution from a few seconds to a minute. In the brain, blood oxygenation and de-oxygenation as well as
rCBF are presumably related to neural activity and are measured by fMRI (or PET). This can be used to measure brain activity when subjects perform specific tasks or are exposed to specific stimuli such as acupuncture.

In this presentation, principles of fMRI and its applications to neuro-imaging with special emphasis to exploration of acupuncture-induced activation of the central nervous system (CNS), the brain will be discussed. Two main lines of acupuncture - cortical correlation studies will be discussed, namely Target-specific and Non-target specific, respectively. Some of the target specific studies include Gb. 37 Guangming and SJ. 5 Waiguan, for visual- and hearing-related acupoints, respectively. In addition to the target specific studies mentioned above, some of the target non-specific acupoint studies will also be discussed, especially in conjunction with pain perception and inhibition by acupuncture. It is found that, with the help of our recently obtained fMRI-acupuncture results, both classical acupuncture analgesia as well as general disease control mechanisms of acupuncture can be formulated and hypothesized.

In summary, with the help of neuro-imaging techniques such as fMRI and PET, it seems possible to study the physiological bases of acupuncture, a millennia old Oriental Medical therapy, by quantitatively examining cortical correlations of acupuncture stimulation, thereby providing clues to "How acupuncture works".

Common Head Ache struggles each of us occasionally without any specific reason. We used to take pain killers to get relief, which in turn damages our liver and other internal organs. Here I am discussing an easy way to get rid of �Common Head Ache� and this remedy is based on SUJOK Acupressure Therapy (A Fast Spreading Korean Treatment). Take a rubber band and tie it tightly on our right thumb (just above the bottom line of the nail). Keep it for 2 minutes. After two minutes remove the rubber band. Your Head Ache must have gone or reduced. If it has not been completely gone, repeat this procedure on the left thumb also�.. Are you ready for a tryout next time?

Low-Level Laser Acupuncture

Traditional Chinese Medicine (TCM) theory states that Qi, or the vital energy, is the living force behind life, all the cosmic forces in nature, and is the root of all things. Most practitioners of Oriental medicine believe that the human being is created when the Qi of Heaven and the Qi of Earth come together. Many also believe that the Qi of Heaven continues to enter the formed human body through the pineal organ in the form of light. We are perhaps starting to recognize, understand, and investigate the profound role light plays in regulating and maintaining health in the human body. Its application to acupuncture is natural.

INTRODUCTION
Just as Traditional Chinese Medicine and acupuncture are very old systems of medicine being rediscovered, so is light therapy. Heliotherapy (light therapy) was practiced by physicians in ancient cultures in Egypt, Greece, China, and India to address many conditions.1 In the 1660s, Isaac Newton separated light with a prism and discovered the visible spectrum. In the 1890s, a Danish physician, Dr Niels Finsen, pioneered light therapy. He observed that tubercular skin lesions were much more common during the long dark winter months, but rare in the summer months. In 1893, he began treating this condition, lupus vulgaris, with light. Later, he would use red light to prevent scar formation from smallpox and eventually established a light institute for the treatment of tuberculosis. So successful was his work in treating skin tuberculosis with ultraviolet light that he was awarded the Nobel prize in 1903. This was the first recognized therapeutic application of an artificial light source.2

In the United States, Dr Dinsha Ghadiali, an American who emigrated from India in the 1800s, also did extensive work with photo therapy, but his alternative approaches to healing were met with resistance and most of his work was destroyed.3 Low-level lasers are still considered investigational in the United States. The US Food and Drug Administration (FDA) has approved some low-level lasers for limited applications. It has been shown that low-level lasers can be effective, but their optimal treatment parameters are not known.

BASIC SCIENCE
Works of the above-mentioned innovators and others provide us with sufficient empirical evidence of the value of light in medicine. The scientific evidence for this rests in quantum physics and the color theory, the photoelectric effect first discovered by Hertz, and the theory of light elucidated by Albert Einstein. According to the photoelectric effect, when light strikes any material substance, electrons are discharged, creating a current. Simply, light interacts with matter as the energy of the light is transferred to the electrons. In 1905, Einstein offered an explanation for this phenomenon with his Corpuscular Theory of Light, for which he was awarded a Nobel Prize.

Einstein proposed that light is composed of corpuscular units called photons. He further claimed that a photon is the smallest unit of light and has a dual nature, being both a particle and a wave at the same time. A photon travels at the speed of light and its energy is related to the frequency of radiation. The energy of the photon is transferred to the electrons when it collides with any material substance. The shorter the waves of light, the greater the energy is transferred to the electron (Figure 1). The intensity of the light determines how many photons strike given surface and how many electrons are, thus, affected. The higher the intensity, the greater the number of photons and therefore, the greater the amount of energy transferred to the electrons. Hence the physics of lasers were first imagined by Einstein.2,4

Color is frequency within the visible spectrum of light. It is composed of a small band of the total electromagnetic spectrum, from violet at 400 nm (higher-energy photon) through red at 700 nm (lower-energy photon) (Figure 2). Beyond violet, in increasingly shorter wavelengths, are ultraviolet light, x-rays, and gamma radiation which contain tremendous amounts of energy. Infrared and radio waves are longer wavelengths outside the red end and less energetics. Each color of the spectrum is composed of a band of frequencies. Therapeutic application of light to the body is accomplished by applying a single monochromatic wavelength within that band.2,4-7

In the 1960s, Theodore Maiman, a physicist, constructed the first laser at Hughes Aircraft Research Laboratories in Malibu, California. The early 1960s saw the development of numerous lasers and numerous new applications in industry and medicine. Many of these new medical applications were in surgery and involved powerful instruments with outputs in the tens-to-hundreds of watts. Surgeons noticed faster healing times and less scarring when doing procedures with lasers than when using the standard scalpel. This was later found to be the result of biostimulation.4

Russian researchers at the Institute for Clinical and Experimental Medicine have shown that light applied to the human skin penetrates the body between 2 and 30 mm, depending on the color frequency. The researchers also found that only certain areas of the body were able to transfer light beneath the surface, and these areas corresponded to acupuncture points. Furthermore, the light was conducted within the body along the acupuncture meridians. It appears that the meridians are a light transferral system within the body somewhat like optical fiber.8

Tina Karu, PhD, of the Laser Technology Center in Russia and affiliated with the University of California at Berkley, has researched the effects of light on the cell since the 1980s. She found there are photo receptors at the molecular level that, when triggered, activate a number of biological reactions such as DNA/RNA synthesis, increased cAMP levels, protein and collagen synthesis, and cellular proliferation. The result is rapid regeneration, normalization, and healing of damaged cellular tissue. Thus, light is a trigger for the rearrangement of cellular metabolism.1,2,4,5,9

In 1966, Endre Mester, a physician in Hungary, performed a series of experiments that showed the biostimulatory effect of visible red and infrared laser light at low intensity. He published his findings in an obscure Hungarian medical journal, which may explain why the benefits of low-level lasers were appreciated in the Eastern bloc long before they were recognized in the West. In the United States, Margaret Naesser, PhD, research professor and acupuncturist at Boston University School of Medicine, conducted research using low-level laser acupuncture with positive results for the treatment of paralysis in patients following stroke and in carpal tunnel syndrome.4

WHAT IS A LASER?
A laser (light amplification by stimulated emission of radiation) is an amplifier of light. It is a specialized environment that will support and sustain stimulated emission. There are 2 properties of laser light that separates it from incandescent light (such as that from a light
bulb).2,4,10

Monochromatic. A laser emits light at a specific wavelength, pure light, rather than over the wide spectral distribution of most light sources. It has a very narrow band width.

Coherent. Laser light is extremely well organized and synchronous (Figure 3). The photons emitted from a laser have been compared to a troop of soldiers marching in precise order.

Two of the most common misconceptions about lasers is that 1) all lasers are high powered, and 2) their beams are always parallel. Conversely, low-level lasers are most often designed with divergent beams as a safety precaution, and they operate at very low levels of power (0.05 to 0.5 W).2,4

Figure 1. Relationship of wavelength to energy


Figure 2. The electromagnetic spectrum




Principles of Use
Low-level laser acupuncture involves the application of photic energy to acupuncture points/tissues with the objective of augmentation of the normal healing process and/or pain relief. The usual wavelengths of lasers that are most commonly used in acupuncture are those that penetrate most deeply due to low absorption in the principal constituent in soft tissues, water.1 Except for the helium-neon laser, currently all therapeutic/low-level lasers use a diode.

Helium-Neon Laser (632.8 nm)
Helium-neon gas mixture. Visible red light. Relatively shallow depth of penetration. Very useful for laser acupuncture, superficial applications, and wound healing. Absorbed by mitochondrial cytochromes. Large, fragile, and expensive instrument (Figure 4).

Indium-Gallium-Aluminum-Phosphorus Laser (633-635 nm)
Now replacing helium-neon lasers. Visible red light, smaller and portable, inexpensive; higher power than the helium-neon, more durable. Same applications as helium-neon (Figure 4).

Gallium-Aluminum-Arsenide Laser (780-890 nm)
Deeper penetration. Near infrared, invisible light. Many applications, inexpensive, very useful for the treatment of pain, but also effective in healing. Most popular therapeutic laser. Valuable to reach very deep acupuncture points or deep Ah Shi points (Figure 4).

Gallium-Arsenide Laser (904 nm)
Greatest depth of penetration, deeper than gallium-aluminum-arsenide. This is due to a much longer wavelength and because they are pulsed, forcing the laser light deep into the tissues. Useful for reaching deep acupuncture points and for the treatment of pain. Continuous wave lasers are now also available (Figure 4).

Mechanism of Action
Energization of depleted enzymes. This may be denatured or depleted in areas of inflammation by hypoxia and acidosis. Examples are:

Sodium Potassium ATPase. Essential for nerve polarization in transmission of an action potential. Low-laser energies (<4 J/cm2 at a given site) tend to increase its concentration and are therefore recommended in cases where nerve regeneration or stimulation is desirable (e.g., Bell's palsy or facial paralysis).1 (The biostimulatory effects of low-level laser are governed by the Arndt-Schulz Law in which low energies stimulate and high energies suppress.1,2,4)

High-laser energies (>4 J/cm2), in contrast, tend to decrease its concentration, therefore being indicated for pain where the object is stabilization of sensitized pain fibers.1

Superoxide Dysmutase. This enzyme breaks down free radicals, which are a cause of pain in trigger areas in myofascial pain.

Transforming Growth Factor (b Fraction). Energization will help accelerate the repair and healing process.1

Vascular Effects. Evidence exists that laser energy is capable of initiating new vessel formation, which is an important factor in the healing process.1,5

Cellular Energization
Cells, after exposure to low-level laser, demonstrate accumulation of energy molecules in the form of ATP.1,5

Overall Effect
Low-level laser photic energy shortens the inflammatory phase, accelerating the repair process, and remodeling after tissue injury. In addition, increased plasma concentrations of certain types of prostaglandins, enkephalins, and endorphins have all been identified and most likely play a major role in the mechanisms associated with pain attenuation.1,5,11

Safety
Low-level lasers are very safe; however, there is a potential for damage to the eye. The laser beam, if directed through the lens of the eye, could damage the retina. Yet in more than 30 years of research and clinical practice, an event of this type has never been reported. Protective goggles that filter out the specific wavelength of the laser light should be worn by the patient and acupuncturist/physician during a therapy session.

To safely operate a laser, the practitioner must thoroughly understand the nature of the equipment.2,4,6,10 Certain technical parameters exist that one must first comprehend. These parameters are the power (for low-level lasers, this is expressed in milliwatts), wavelength, the characteristics of the laser beam (its optics; such as divergence, convergence, or parallel nature of the beam). All these influence the level of risk. Obviously, a high-power laser is riskier than a lower-power one. An infrared laser is riskier to use than a visible, red light laser with the same power and beam characteristics because the light is invisible and does not promote a blink response.2,4,6,10

INDICATIONS
The following is a partial list of conditions that have shown promising results with laser acupuncture. Laser acupuncture is painless and may be offered to patients with needlephobia and to children.1,2,4,10-18

Acute/chronic pain


TMJ dysfunction

Paresthesias


Cervical/lumbar spine syndromes

Neuralgias


Dermatoses

Allergic rhinitis/sinusitis


Asthma

Frozen shoulder


Phantom pain

Arthritis/arthrosis


Fibromyalgia

Bursitis, tendonitis


Nerve regeneration

Carpal tunnel syndrome


Wound healing

In addition, most lasers may be used in all instances for which moxibustion is indicated. There is no reducing or tonifying technique when performing laser acupuncture. Low-level lasers when used in pulsed mode have significant effects that may correspond with central bioresonances. The following frequencies are suggested from prior research studies.1,2,4,10,17,18

2 Hz


Nerve regeneration, neurite outgrowth

7 Hz


Bone growth

3-20 Hz


Pain

700-2500 Hz


Stimulatory effect

>2500 Hz


Inflammation, edema

>5000 Hz




Laser acupuncture may be combined with regular needle acupuncture at the same time with other forms of energy medicine (e.g., homeopathy, Chinese herbs, etc), and with medications such as anticonvulsants and antidepressants in chronic pain management, thereby reducing their dosage.

DISCUSSION
No doubt, the FDA will continue to approve the use of lasers for a variety of conditions (recently, a laser company in the United States received approval for the treatment of carpal tunnel syndrome). There are FDA guidelines that govern the use of low-level lasers as an investigational device, as well as state regulations. The FDA classifies low-level lasers as class IIIB non-significant risk devices.

CONCLUSION
Low-level lasers are used extensively in Europe and Asia for many applications, including acupuncture. Low-level lasers may be an effective modality in battling many situations. More research is needed to establish ideal treatment parameters for specific conditions.

Figure 3. Comparison of laser and other light sources


Figure 4. Relative depth of various lasers commonly used in acupuncture




REFERENCES

1. Bradley PF. Laser basics: principles of low intensity laser therapy (LILT). Presented at: Third Annual Conference of the North American Association for Laser Therapy.
2. Tuner J, Hode L. Laser Therapy: Clinical Practice and Scientific Background. Gransgesberg, Sweden: Prima Books; 2002.
3. Dinsha D. Let There Be Light. Malaga, NJ: Dinsha Health Society; 1996.
4. Blahnik JA, Rindge DW. Laser Therapy: A Clinical Manual. Melbourne, FL: Healing Light Seminars Inc; 2003.
5. Karu T. The Science of Low Power Laser Therapy. Amsterdan, the Netherlands: Gordon and Beach Science Publishers; 1998.
6. Oshiro T, Calderhead RG. Low Level Laser Therapy: A Practical Introduction. Chichester, England: John Wiley & Sons Ltd; 1988.
7. Mandel P. Practical Compendium of Colorpuncture. Bruchsal, Germany: Ditton Energetik; 1986.
8. Pankratov S. Meridians Conduct Light. Germany: Raum & Zeit; 1991.
9. axter DG. Therapeutic Lasers: Theory and Practice. New York, NY: Churchill Livingstone; 1994.
10. Naesser M. Laser Acupuncture: An Introductory Textbook for Treatment of Pain, Paralysis, Spasticity and Other Disorders (Clinical and Research Uses of Laser Acupuncture From Around the World). Boston, MA; Boston Chinese Medicine; 1994.
11. Moore K. Lasers and Pain Treatment. Cinixeperience: Laser Partner. Official paper of the Czech Society for the Use of Laser in Medicine. February 26, 2004.
12. Braverman B, et al. Effects of helium-neon and infrared laser irradiation on wound healing in rabbits. Lasers Surg Med. 1989;9:50.
13. Rochkind S, et al. Systemic effects of helium-neon laser irradiation on the peripheral and central nervous system, cutaneous wound and burns. Lasers Surg Med. 1982;26:12.
14. Ariaksinen O, et al. Effects of helium-neon laser irradiation on the trigger points of patients with chronic muscle tension in the neck. Scand J Acupuncture Electrother. 1989;3:63-65.
15. Ponnuradai RN, et al. Hypoalgesic effect of laser photobiostimulation shown by rat tail flick test. Int J Acupunct Electrother Res. 1987;12:93-100.
16. Mokhtar B, et al. A double blind placebo controlled investigation of the hypoalgesic effect of low intensity laser irradiation of the cervical roots using experimental ischemic pain. Presented at: ILTA Congress; London, England; 1992. Abstracts :61.
17. Mokhtar B et al. The possible significance of pulse repetition rate in laser mediated analgesia: a double blind placebo controlled investigation using experimental ischemic pain. Presented at: ILTA Congress; London, England; 1992. Abstracts :62.
18. Kucerova H, et al. Modulatory frequency of lasers in connection to laser beam therapeutic effect. Proc SPIE. 1998;3248L:191-195. Lasers in Dentistry IV.
Author: Jose T. Vargas is a Board-certified acupuncturist, specializing in laser acupuncture. He is a Senior Physician Assistant for the Department of Medicine at Montefiore Medical Center of the Albert Einstein College of Medicine in New York City, and a faculty member at New York College of Traditional Chinese Medicine in Mineola, NY.
Jose T. Vargas, MSc, LAc, PA-C*

Background

Astrocytomas are CNS neoplasms in which the predominant cell type is derived from an immortalized astrocyte. Two classes of astrocytic tumors are recognized�those with narrow zones of infiltration (eg, pilocytic astrocytoma, subependymal giant cell astrocytoma, pleomorphic xanthoastrocytoma) and those with diffuse zones of infiltration (eg, low-grade astrocytoma, anaplastic astrocytoma, glioblastoma). Members of the latter group share various features, including the ability to arise at any site in the CNS, with a preference for the cerebral hemispheres; clinical presentation usually in adults; heterogeneous histopathological properties and biological behavior; diffuse infiltration of contiguous and distant CNS structures, regardless of histological stage; and an intrinsic tendency to progress to more advanced grades.

Numerous grading schemes based on histopathologic characteristics have been devised, including the Bailey and Cushing grading system, Kernohan grades I-IV, World Health Organization (WHO) grades I-IV, and St. Anne/Mayo grades 1-4. Regions of a tumor demonstrating the greatest degree of anaplasia are used to determine the histologic grade of the tumor. This practice is based on the assumption that the areas of greatest anaplasia determine disease progression.

This chapter focuses on the widely accepted WHO grading scheme that relies on assessments of nuclear atypia, mitotic activity, cellularity, vascular proliferation, and necrosis. WHO grade I corresponds to pilocytic astrocytoma, WHO grade II corresponds to low-grade (diffuse) astrocytoma, WHO grade III corresponds to anaplastic astrocytoma, and WHO grade IV corresponds to glioblastoma multiforme (GBM). This article is confined to low-grade and anaplastic astrocytomas. GBM and pilocytic astrocytoma are not discussed in this article
Pathophysiology

Regional effects of astrocytomas include compression, invasion, and destruction of brain parenchyma. Arterial and venous hypoxia, competition for nutrients, release of metabolic end products (eg, free radicals, altered electrolytes, neurotransmitters), and release and recruitment of cellular mediators (eg, cytokines) disrupt normal parenchymal function. Elevated intracranial pressure (ICP) attributable to direct mass effect, increased blood volume, or increased cerebrospinal fluid (CSF) volume may mediate secondary clinical sequelae. Neurological signs and symptoms attributable to astrocytomas result from perturbation of CNS function. Focal neurological deficits (eg, weakness, paralysis, sensory deficits, cranial nerve palsies) and seizures of various characteristics may permit localization of lesions.

Infiltrating low-grade astrocytomas grow slowly compared to their malignant counterparts. Doubling time for low-grade astrocytomas is estimated at 4 times that of anaplastic astrocytomas. Several years often intervene between the initial symptoms and the establishment of a diagnosis of low-grade astrocytoma. One recent series estimated the interval to be approximately 3.5 years. The clinical course is marked by a gradual deterioration in one half of cases, a stepwise decline in one third of cases, and a sudden deterioration in 15% of cases. Seizures, often generalized, are the initial presenting symptom in about one half of patients with low-grade astrocytoma.

For patients with anaplastic astrocytomas, the growth rate and interval between onset of symptoms and diagnosis is intermediate between low-grade astrocytomas and glioblastomas. Although highly variable, a mean interval of approximately 1.5-2 years between onset of symptoms and diagnosis frequently is reported. Compared to low-grade lesions, seizures are less common among patients with anaplastic astrocytomas. Initial presenting symptoms most commonly are headache, depressed mental status, and focal neurological deficits..
Mortality/Morbidity

Morbidity and mortality, as defined by the length of a patient's history and the odds of recurrence-free survival, are correlated most highly with the intrinsic properties of the astrocytoma in question. Typical ranges of survival are approximately 10 years from the time of diagnosis for pilocytic astrocytomas (WHO grade I), more than 5 years for patients with low-grade diffuse astrocytomas (WHO grade II), 2-5 years for those with anaplastic astrocytomas (WHO grade III), and less than 1 year for patients with glioblastoma (WHO grade IV).
Race

Although genetic determinants are recognized in astrocytoma development and progression, astrocytomas do not differ intrinsically in incidence or behavior among racial groups. Demographic and sociological factors, such as population, age, ethnic attitude toward disease, and access to care, have been reported to influence measured distributions.
Sex

No clear sex predominance has been identified in the development of pilocytic astrocytomas. A slight male predominance, with a male-to-female ratio of 1.18:1 for development of low-grade astrocytomas, has been reported. A more significant male predominance, with a male-to-female ratio of 1.87:1 for the development of anaplastic astrocytomas, has been identified.
Age

Most cases of pilocytic astrocytoma present in the first 2 decades of life. In contrast, the peak incidence of low-grade astrocytomas, representing 25% of all cases in adults, occurs in people aged 30-40 years. Ten percent of low-grade astrocytomas occur in people younger than 20 years; 60% of low-grade astrocytomas occur in people aged 20-45 years; and 30% of low-grade astrocytomas occur in people older than 45 years. The mean age of patients undergoing a biopsy of anaplastic astrocytoma is 41 years.
History

The type of neurological symptoms that result from astrocytoma development depends foremost on the site and extent of tumor growth in the CNS. Reports of altered mental status, cognitive impairment, headaches, visual disturbances, motor impairment, seizures, sensory anomalies, or ataxia in the patient's history should alert the clinician to the presence of a neurological disorder and should indicate a requirement for further studies. In this event, radiographic imaging, such as CT scan and MRI (with and without contrast), is indicated. Astrocytomas of the spinal cord or brainstem are less common and present with motor/sensory or cranial nerve deficits referable to the tumor's location.
Physical

* A detailed neurological examination is required for the proper evaluation of any patient with an astrocytoma. Because these tumors may affect any part of the CNS, including the spinal cord, and may spread to distant regions of the CNS, a thorough physical examination referable to the entire neuraxis is necessary to define the location and extent of disease.
* Special attention should be paid to signs of increased ICP, such as headache, nausea and vomiting, decreased alertness, cognitive impairment, papilledema, or ataxia, to determine the likelihood of mass effect, hydrocephalus, and herniation risk. Localizing and lateralizing signs, including cranial nerve palsies, hemiparesis, sensory levels, alteration of deep tendon reflexes (DTRs), and the presence of pathological reflexes (eg, Hoffman and Babinski signs), should be noted. Once neurological abnormalities are identified, imaging studies should be sought for further evaluation.
Causes

* The etiology of diffuse astrocytomas has been the subject of analytic epidemiological studies that have yielded associations with various disorders and exposures. With the exception of therapeutic irradiation and, perhaps, nitroso compounds (eg, nitrosourea), the identification of specific causal environmental exposures or agents has been unsuccessful.
* Children receiving prophylactic irradiation for acute lymphatic leukemia (ALL), for example, have a 22-fold increased risk of developing CNS neoplasms in WHO grade II, III, and IV astrocytomas, with an interval for onset of 5-10 years. Furthermore, irradiation of pituitary adenomas has been demonstrated to carry a 16-fold increased risk of glioma formation.
* Evidence exists for genetic susceptibility to glioma development. For example, familial clustering of astrocytomas is well described in inherited neoplastic syndromes, such as Turcot syndrome, neurofibromatosis type 1 (NF1) syndrome, and p53 germ line mutations (eg, Li-Fraumeni syndrome).
* Biological investigation has implicated that mutations in specific molecular pathways, such as the p53-MDM2-p21 and p16-p15-CDK4-CDK6-RB pathways, are associated with astrocytoma development and progression. In addition, inherited elements of the immune response known as human leukocyte antigens (HLA) have been both positively and negatively associated with an increased risk for the development of glioblastoma multiforme.
* Recently, attempts have been made to determine prognosis and response to various treatment modalities based on the individual pattern of genetic changes in a particular patient. For example, patients with oligodendrogliomas that exhibit chromosomal changes at band 1p19q are known to have improved responses to the procarbazine, CCNU, vincristine (PCV) regimen of chemotherapy. Efforts are underway to identify similar unique susceptibilities associated with other commonly altered genes and proteins in astrocytomas. Other groups are working on developing models that will
Lab Studies

* No laboratory studies diagnostic of astrocytoma currently exist. Baseline laboratory studies, including Chem 7, CBC, prothrombin time (PT), and activated partial thromboplastin time (aPTT), may be obtained for general metabolic surveillance and preoperative assessment.

Imaging Studies

* CT scans and MRI (with and without contrast) are helpful in the diagnosis, grading, and pathophysiological evaluation of astrocytomas. MRI is considered the criterion standard, but a CT scan may be useful in the acute setting or when MRI is contraindicated.
* On a CT scan, low-grade astrocytomas appear as poorly defined, homogeneous, low-density masses without contrast enhancement. However, slight enhancement, calcification, and cystic changes may be evident early in the course of the disease. In cases where a cortically based enhancing mass is discovered, particularly in cases where multiple lesions are identified, the possibility of metastatic disease must be considered. Systemic imaging, generally consisting of a contrast-enhanced CT scan of the chest, abdomen, and pelvis, may be warranted to evaluate for the possibility of an alternate primary lesion.
* Similarly, anaplastic astrocytomas may appear as low-density lesions or inhomogeneous lesions, with areas of both high and low density within the same lesion. Unlike low-grade lesions, partial contrast enhancement is common.
* Astrocytomas generally are isointense on T1-weighted images and hyperintense on T2-weighted images. While low-grade astrocytomas uncommonly enhance on MRI, most anaplastic astrocytomas enhance with paramagnetic contrast agents. New methods are being developed to assess tumor vascularity by MRI, including techniques such as arterial-spin labeling (ASL) and dynamic contrast-enhanced MRI.
* Angiography may be used to rule out vascular malformations and to evaluate tumor blood supply. A normal angiographic pattern or a pattern consistent with an avascular mass that displaces normal vessels usually is observed
Other Tests

* Because seizure activity often is associated with astrocytomas, EEG may be employed to evaluate and monitor epileptiform activity.
* Radionuclide scans, such as positron emission tomography (PET), single-photon emission tomography (SPECT), and technetium-based imaging, can permit study of tumor metabolism and brain function. PET and SPECT may be used to distinguish a solid tumor from edema, to differentiate tumor recurrence from radiation necrosis, and to localize structures.
* Metabolic activity determined by radionuclide scans can be used to determine the grade of a lesion. Hypermetabolic lesions often correspond to higher-grade tumors.
* ECG and chest radiographs are indicated to evaluate operative risk.

Procedures

* A lumbar puncture (LP) in patients with cerebral astrocytomas should be approached with extreme caution because of the risk of downward cerebral herniation secondary to elevated ICP. Although CSF studies are not employed in the diagnosis of astrocytomas, they may be employed to rule out other possible diagnoses, such as metastasis, lymphoma, or medulloblastoma.

Histologic Findings

Four histological variants of low-grade astrocytomas are recognized�protoplasmic, gemistocytic, fibrillary, and mixed.

1. Protoplasmic astrocytomas generally are cortically based, with cells containing prominent cytoplasm. Protoplasmic astrocytomas constitute approximately 28% of infiltrating astrocytomas.
2. Gemistocytic astrocytomas generally are found in the cerebral hemispheres in adults and are composed of large round cells with eosinophilic cytoplasm and eccentric cytoplasm. Gemistocytic astrocytomas constitute 5-10% of hemispheric gliomas.
3. Fibrillary astrocytomas, the most frequent histological variant, resemble cells from the cerebral white matter and are composed of small, oval, well-differentiated cells. The tumors are identified by a mild increase in cellularity and fibrillary background. Markers for glial fibrillary acidic protein (GFAP) are
Staging

Staging is not performed or described for patients with astrocytoma. The histologic grade of the tumor is of primary importance when determining prognosis. Unlike other systemic tumors, distant or extracranial metastasis of astrocytomas is exceedingly rare. Clinical decline and tumor-associated morbidity and mortality are almost always associated with local mass effects on the brain by a locally recurrent intracranial tumor.
Surgical Care

The roles of surgery in the patient with astrocytoma are to (1) remove or debulk the tumor and (2) provide tissue for histological diagnosis, permitting tailoring of adjuvant therapy and assessment of prognosis. A stereotactic biopsy is a safe and simple method for establishing a tissue diagnosis. The use of stereotactic biopsy can be limited by sampling error and the risk of biopsy-induced intracerebral hemorrhage. Diversion of CSF by external ventricular drain (EVD) or ventriculoperitoneal shunt (VPS) may be required to decrease ICP as part of nonoperative management or prior to definitive surgical therapy if hydrocephalus is present.

Total resection of astrocytoma is often impossible because the tumors often invade into eloquent regions of the brain and exhibit tumor infiltration that is only detectable on a microscopic scale. Therefore, surgical resection only provides for improved survival advantage and histological diagnosis of the tumor rather than offering a cure. However, craniotomy for tumor resection can be performed safely and is generally undertaken with the intent to cause the least possible neurological injury to the patient.
Consultations

* A neurologist should be consulted to document a patient's detailed neurological examination. This establishes a baseline and partly assesses the possibility of occult disease. Employing multiple modalities, the neurologist must correlate symptomatology with anatomic and functional imaging. This physician also may manage antiepileptic medication for patients manifesting seizures.
A neurooncologist may be consulted to help coordinate a comprehensive therapeutic plan. Once a histological diagnosis is determined, the neurooncologist should be consulted to provide comprehensive adjunctive therapy, including the use of chemotherapy and radiation.

Activity

* No broad restrictions on activity are prescribed, other than those dictated by the nature and the extent of neurological symptoms and disability.
* Seizures, if uncontrolled, may preclude driving.
* Physical and occupational therapy may be required for recovery of full or partial function.
Further Inpatient Care

* Management of low-grade astrocytomas is controversial. The tumors may be radiographically stable and clinically quiescent for long periods after the initial presentation.
* Therapeutic options include observation, radiation, and resection with and without radiation. Unless an astrocytoma is resected completely, radiation therapy should be considered.
* In higher-grade lesions, even if gross total resection is confirmed radiographically, postoperative radiation is indicated because microscopic disease remains.
* If no resection is undertaken and radiation is contemplated, a stereotactic biopsy is recommended to establish the histological grade of the tumor definitively.

Further Outpatient Care

* Patients should consult a neurologist to observe the progression of neurological signs and symptoms and to manage steroid and anticonvulsant regimens.
* Outpatient neurosurgery observation is necessary for tumor monitoring and management of hydrocephalus if a shunt has been placed.
* Postoperative and postirradiation chemotherapy trials using nitrosourea and other agents are likely to benefit patients with malignant astrocytomas, but the benefit for patients with well-differentiated astrocytomas is questionable.
* Frequency of postoperative MRI is determined by both the neurosurgeon and other physicians involved in the ongoing care of the patient, including the neurooncologist and radiation oncologist.
In/Out Patient Meds

* Corticosteroids, antiepileptic agents, and GI prophylaxis should be employed.

Transfer

* If surgery is anticipated, patients should be transferred to institutions with an appropriately equipped and adequately staffed neurosurgical intensive care unit for postoperative monitoring.
* Patients may require extensive or focused postoperative rehabilitation that may necessitate transfer to specialized institutions dedicated to physical and occupational therapy.

Complications

* Although neurological injury (potentially devastating) and death must be mentioned, neurosurgery for astrocytomas is generally intended to decrease tumor bulk while avoiding permanent neurological injury. Transient deficits due to local swelling or injury may occur, but they often improve after a course of physical therapy and rehabilitation.

Prognosis

* Prognosis for survival after operative intervention and radiation therapy can be favorable for low-grade astrocytomas.
* For those patients who undergo surgical resection, the prognosis depends on whether the neoplasm progresses to a higher-grade lesion.
* For low-grade lesions, the mean survival time after surgical intervention has been reported as 6-8 years.
* In the case of anaplastic astrocytoma, symptomatic improvement or stabilization is the rule after surgical resection and irradiation. High-quality survival is observed in 60-80% of these patients. Factors such as youth, functional status, extent of resection, and adequate irradiation affect the duration of postoperative survival.
* Recent reports indicated that irradiation of incompletely resected tumors increased 5-year postoperative survival rates from 0-25% for low-grade astrocytomas and from 2-16% for anaplastic astrocytomas. Furthermore, the median survival rate of patients with anaplastic astrocytoma who undergo both resection and irradiation has been reported to be twice that of patients receiving only operative therapy (5 y vs 2.2 y)..
* Failure to make an appropriate diagnosis of astrocytoma is a pitfall that should be avoided by adhering to a systematic diagnostic approach, including imaging studies and obtaining adequate tissue for analysis.
* Timing of diagnosis is particularly important when lesions abut crucial brain nuclei or eloquent cortex. The extent of lesion resectability may be affected by delay.
* Clear explanation of all therapeutic options and prognosis once a diagnosis is established is essential.

Apart from the deep acting constitutional remedies like Phosphorus, Lycopodium, Pulsatilla, Nux vomica and Sepia, the other remedies that may help in tackling the fatigue are:

Kali phos: This is the chief Biochemic "nerve salt," and is found in the brain cells and nerve fluids, and the intercellular fluids. It is useful for patients with despondency, anxiety, fearfulness, weak memory, mental decay, mental and physical breakdown, neurasthenia, hypochondriasis, hysteria, insomnia, night terrors, irritability, insanity and paralysis. This salt has proved curative in nervousness, neurasthenia, anxiety, depression, brain-fag, loss of memory, sleeplessness, delirium tremens, horrors, dread, epileptic fits, and exhaustion.

Phosphoric acid: This remedy is to nervous debility what iron is to anemia, and it corresponds to that debility arising from continued grief, over- exertion of the mind, sexual excesses or any nervous strain on the body or mind. Indifference, apathy, and torpidity of body and mind characterize the remedy. There is burning in the spine and limbs and the patient is inclined to be drowsy and listless. Any attempt to study causes heaviness in the head and limbs. It suits also young, rapidly growing people, and especially cases of nervous depression from spermatorrhoea.

Gelsemium: A mainstay in this disease. Stupid, dull, unable to concentrate mind; vertigo, dull ache at base of brain. Lacks self-confidence. Sudden emotions bring on diarrhoea or indigestion.

Picric acid: Corresponds well to the brain fag of businessmen who become depressed and wearied from slight fatigue. It is a mental inactivity, with a desire to lie down and rest. The great characteristic is that slight exertion brings on exhaustion and headache, incapacitating for work, and extinguishes that quality which we call grit. Even the slightest mental exertion causes heavy feelings and a sensation of heat. The headache may be frontal or occipital and extended down the spine, in fact, the head symptoms seems to be concentrated in the occiput. Sexual irritability may be a prominent symptom. In the morning there is a tired aching in the lumbar region, the legs are heavy and weak with the soreness of the muscles and joints.

Avena sativa: Has a selective action on brain and nervous system, favorably influencing their nutritive function. Weakness of nerves, tired brain, irritability, gets excited at least thing. Urine has excess of phosphates, history of sexual excesses and occipital headache. Best tonic for debility after exhausting diseases. Nerve tremors of the aged. Sleeplessness in alcoholics. This remedy will calm and strengthen the nerves.