To a new understanding of personality, behavior and neurological disease
W. Hammesfahr, M.D.
D. Adkins, REEG.T
Hammesfahr Neurological Institute
Copyright Â© 1997 MedForum. All rights reserved.
With a long history of medical investigation behind, diseases affecting the brain, nervous system, and psyche have been named, categorized, classified and recategorized again. The diseases bear names of those who first described them, a common pathological finding, or bear the name of their primary clinical symptom. Such naming protocols rarely name aetiology or cause, as the cause is rarely known.
Yet we have found that a large number of apparently diverse neurological, psychological, or psychiatric diseases share a common underlying disorder, that of chronic or intermittent ischemia1 of the brain. The disparate clinical manifestations of that disorder2, depends on the acute or chronic onset of the disorder, the rapidity of the evolution of an underlying vascular disorder, the age of the patient when the disorder develops, other medications that the patient may be on which helps to limit or aggravate the underlying vascular disorder, and the body’s ability to compensate for this disorder.
We have further found that all of these disorders2 respond similarly to techniques that correct the underlying vascular/ischemic disorder.
In essence, most of the neurological diseases associated with chronic ischemia result in either cognitive disorders or chronic degenerative neurological states. Thus Autism, Attention Deficit Disorder and similar syndromes, including Tourette’s, many cases of Depression, psychosis, and other neuropsychiatric disorders are frequently seen in a chronic ischemia. In some cases, the chronic ischemic state results in a degenerative neurological condition. Thus, ongoing ischemia may mimic what we more commonly diagnose patients with diagnosis of Alzheimer’s, Multiple Sclerosis, and Parkinson’s. In others with these diagnoses, there may be a an underlying chronic vascular ischemia which also aggravates the original condition, and is clinically indistinguishable. That vascular portion of their disease may be entirely reversible. When the problem develops rapidly, physical symptoms predominate. Thus patients are diagnosed as Migraine Headache, Stroke, Closed Head Injury, Ataxia, Vertigo, Tinnitis, Fibromyalgia, etc.
As few will read beyond these opening remarks, the headache deserves special mention. In our experience, it is the equivalent of Angina. In Angina, blood vessels downstream from a partial blockage dilate as one of the body’s most important mechanism to compensate for a decrease in blood flow. As such, this dilations helps to preserve blood flow to the tissue. This dilation stretches the nerve fibers in the walls of the arteries, which results in pain. Similarly, the headache in our patients represents one of the body’s compensatory mechanisms used to increase blood flow in response to a blockage. As the patient’s vascular disorder becomes chronic, the body develops other compensatory mechanisms. By developing these other mechanisms, the headache becomes a more infrequent and less noticed clinical problem. As the body develops the ability to compensate, the physical symptoms become less noticeable, and the cognitive/emotional/behavioral disturbances become the major problems3. Thus, as the patient recovers, it becomes vitally important to be aware that the patient’s symptoms will vary and alter as the vascular disorder improves. Indeed, many of these symptoms become less of one specialty’s province, and becomes that of another’s. Thus, the managing physician and patient need to continue to consider the entire range of symptoms as “ischemia/vascular equivalents”, and continue to treat all symptoms aggressively. The present or past history of headache or family history of migraine, becomes incredibly important in understanding that patient’s disorder may have a vascular component.
What follows is a discussion of the development of our experience.
I have a baseline practice consisting of mainly post-traumatic, closed-head injuries and post-traumatic migraine disorders of which many have attention deficit disorders, (ADD). However, several years ago I had a large number of patients who presented with ADD of which the origin of their problems was associated with silicon breast implants (silicon toxicity). What became evident in evaluating of these patients was that the neuropsychological tests, computerized EEG and Transcranial Artery Doppler results were essentially identical. Another common characteristic in these patients was the waxing and waning nature of at least some of their complaints. Those patients with Attention Deficit Disorder both post-traumatic and in particularly those patients with silicon breast implant disease with MS-like syndrome would have normal neurological examination one day and on another day the exam would be abnormal. This finding substantiated the patients’ complaints of waxing and waning of symptoms and seemed to be related to the degree of physiological or psychological stress the patient experienced when being interviewed or tested.
The degree of abnormality of neurological exams would extend to the point of normal or abnormal Romberg and Tandem Gaits, reflex examinations and Babinski examinations in the same patient. Evoked potential test results varied from normal to abnormal on different days and the testing was performed by the same examiners.
In this same time frame, a series of new medications were developed to treat migraine headaches. As headache was a major complaint of many of my patients, we tried these medications out including Imitrex (Sumatriptan), IM Toradol (Ketoralac) and other medications under direct monitoring. As my patients tend to be intractable, it was not expected that any of these medications would have dramatic results. Rather, it was expected that one or another set of medications might help point the way into using specific classes of medications or approaches. Accordingly, each of these patients, equivalent of a large number of patients, were monitored continuously across the day. The patients would come in and be hooked up with EEG’s or Brain Stem Auditory Evoked Responses, or VEP’s, or Transcranial Dopplers, and across the day would have many of the different short-acting medications tried on them to see which would work and which monitoring tool would be most effective in identifying the improvement.
With respect to the different monitoring tools, some were more helpful than others. It was found that the EEG was not very sensitive. The Brain Stem Auditory Evoked Response and other evoked potential tests were very insensitive tools for monitoring, because of the length of time required to perform the test after short-acting medications were given in IM or sublingual or nasal spray administration route. The Transcranial Doppler consistently appeared to give the best indication as to which medications would work. If an ultrasound showed improvement, the patient invariably also reported improvement in their clinical symptoms. These symptoms included not only headache, but also sensations of confusion, balance disorder, abnormal Romberg or Tandem Gait or other neurological abnormalities. If the medications showed evidence of increasing vasoconstriction on the doppler, the patients who had a headache, frequently reported improvement in the headache, but a worsening of their confusional state or a worsening of other neurological symptoms. Those patients were identified as having improvement on ultrasound with doppler also showed resolution of their headache, but did not show the deterioration in other neurological effects.
This was completely unexpected. The general approach towards migraine and headache has always been that the headache represents a vasodilation and frequently a hyperperfusion state. The aura, of course, represents a vasoconstrictive phase. What our results seemed to suggest was that the doppler, which looks at essentially
the area of blood vessels around the base of the brain, was showing vasoconstriction. Vasoconstrictive medicines would relieve the headache presumably through a similar mechanism, as a vasoconstrictive medication probably relieved coronary artery disease. It would relieve it by decreasing the vasodilation that occurs downstream from the area we are able to directly insonate. Unfortunately, if cerebral artery disease is anything like coronary artery disease, that downstream dilation represents an attempt by the body to compensate and maintain perfusion to thus becoming ischemic.
In my patient population all medications which resulted in vasoconstriction, relieved the headache, but caused neurological deterioration. As the medication wore off, as documented by the patient’s clinical symptoms, sonography data, the patient’s neurological abnormalities improved. Similarly, those medicines which resulted in direct vasodilation such as Hydralazine (Apresoline), Nitroglycerin and other medications all resulted in improvement in the patient’s headache, but also resulted in improvement of any other neurological abnormalities including balance disorders, gait disorders, hemiparesis, abnormal Babinski’s and abnormal reflexes.
It was found that with aggressive treatment to result in radiological and clinical vasodilation of the vasculature, patients frequently became neurocognitively, psychologically, and symptomatically cured. However, if the medications, and monitoring was then stopped, whatever underlying disorder that caused the vasospasm in the first place, caused it to re-occur. When the patient’s clinical ischemia first re-occurred, it generally was not with the same symptoms as they first presented. Rather, the symptoms were generally more mild and in the neurocognitive arena or mild physical disability. Thus, the first symptoms to re-occur tended to be mild confusional/distraction states, or disorders of mood. These disorders of mood, attention, and concentration could vary across the day as well as across longer periods of time. Thus patients frequently showed emotional lability or other disorders of attention, memory, and mood that were intermittent or chronic depending on the degree of the chronicity of the vasospasm and its severity or periodicity. Occasionally, mild ataxias, apraxias, or visual blurring would predominate in these early phases. If left untreated, the patient’s symptoms usually slowly deteriorated over months into similar symptoms as they first presented.
OBSERVATIONS NOTED CONCERNING TRANSCRANIAL DOPPLERS
As alluded to earlier, we have found that Transcranial Dopplers are the most cost effective means of monitoring the vasospasm and guiding medical therapy. Due to their importance, a special word about Transcranial Doppler needs to be made.
We found that morphology of a Transcranial Doppler Artery Ultrasound is as important as mean flow velocities. In our patients, as they became more normal, and as their fixed deficits and neuropsycho-logical abnormalities resolved etc., the morphology of the wave form would be similar to that of an internal carotid artery tracing. We did not find that there would be elevation of flow readings throughout diastole, as is more commonly published. It is important to identify that the original normative data obtained in 1979, used for “Normals” patients with post-traumatic migraine disorders, “psychogenic seizures”, and the interictal migraine phase may not be appropriate. It is important to note that other labs which have done less extensive studies of normal versus non-normal, may have unknowingly used many patients with a history of migraines or whiplash headaches.
Some have not identified the close relationship between degree of vasospasm and clinical abnormalities. This may be due to less lengthy monitoring or evaluations being carried out by those labs in comparison to our own. Equally, the trend clinical correlation is a general one. Remembering hemodynamics, it is important to note that if the blood vessel is constricted, patients do have a limited ability to compensate for the effects of that vasoconstriction by dilating distally to the constricted area. Patients will not be abnormal clinically during the early stages of constriction of an artery. It is only once the downstream area is no longer able to dilate to a degree enough to maintain a significant pressure gradient across the vasoconstricted area that the patient will develop symptoms. It is important to continue to monitor and treat these patients until the sonographic studies return to normal and beyond. Realizing that blood vessels constrict across the day in response to sympathetic nervous system variability, internal steroid release, physiological and psychological stress, including the physiological stress of photic stimulation, driving etc., and thus to obtain an ultrasound at one moment, must be correlated with the patient’s clinical symptoms and any complaints of variability across the day.
We also found that over time, chronic, untreated patient studies frequently falsely appear to normalize with a dropping of mean flow velocities. This occurs as the body develops compensating mechanisms to relieve the ischemia. Thus morphology becomes extremely important in identifying those who have ongoing vasoconstrictive disorder intracranially. The development of a pattern as time goes on is to have a blunted upstroke in the systolic portion of the ultrasound, but with an overall mean flow velocity of less than .6 meters per second. That blunting, which is also seen in disseminated vascular disease from any cause, is highly suspicious for severe vasospastic disorder. A computerized EEG or standard EEG consistent with brain dysfunction or ischemia, and/or neuropsych testing consistent with variability of cognitive injury (especially with fluctuating cognitive deficits across several hours or days of testing) with ischemia is often helpful as a corraborating study. These are patients who should not be treated initially with Nitroglycerin or other potent medications, but should first have other medications which are direct vasodilators instituted at low doses and slowly advanced as the patient is able to tolerate it. This institution with alternative vasodilators, tends to decrease the incidence of a potentially dangerous nitric oxide sensitivity reaction.
Specifics of Experience with Medications
We have used multiple medications for the outpatient treatment of vasospastic disease. Nitroglycerin was the first major successful drug that could be safely and repetitively used by the patient. However, our experience has been considerably developed since that time. Essentially, though, all vasodilating medications have the may be used. Specific choices will depend on patient efficacy, clinical response, patient compliance, and success in reversing the disorder as monitored by objective testing.
With respect to Nitroglycerin, what we have seen is several time courses of the effect of Nitroglycerin. The first is an acute effect which lasts between 15 and 45 minutes. The method of
administration being a patch, pill or sublingual spray determines the rapidity of absorption and distribution. It seems to have a lingering effect for approximately 2 to 3 hours. Nitroglycerin then gets converted into a variety of subsidiary byproducts, all
with some vasodilating properties. Each of these medications themselves can accumulate in patients to toxic doses, and can cause a reactive cerebral vasoconstriction. Thus, it is easier to maintain patients on intermittent low dose Nitroglycerin applications, then chronic applications of medication, as the clinical data and clinical response to the vasodilator challenge becomes confused. With respect to Nitric Oxide sensitivity, those patients in my clinical practice who have not been premedicated with a beta blocker, an alpha blocker or a direct vasodilator such as a calcium channel blocker or an ACE inhibitor, who are given their first dose of Nitric Oxide and developed acute erythema of the nose or face, are having a reactive vasoconstriction and distal vasodilation occurring at the same time. Those patients on
Transcranial Doppler Artery Ultrasound will have acute spasm of the arteries and active constrictions and dilations may frequently be seen. Those patients may have a seizure or a stroke or a blackout spell. This problem can be immediately reversed with IM Toradol(ketoralac). Toradol in 90 to 120 mg IM doses causes acute vasodilation on ultrasound in most patients. In lower doses, the Transcranial Doppler Artery Ultrasounds generally do not show significant changes, but the patient reports a symptomatic improvement. For most patients, standard doses of nitrates in any form will aggravate the vasospasm.
IV Toradol (Ketorolac) in 30 to 60 mg doses does not cause any improvement on Transcranial Doppler Artery Ultrasound, and patients generally report a sensation of vertebrogenic syndrome with increase spaciness, confusion, worsening headache and worsening spasm. Although I have not identified this directly, their clinical course is that of a development of a vasoconstricted vertebral or basilar artery syndrome. This probably relates to a carrier drug in the I.V. Toradol solution, as giving the Toradol intramuscularly (I.M.) or in the alternative oral form after oral or I.M. loading gives the expected vasodilation. Without a change in formulation, I would not recommend the I.V. use of Toradol to reverse acute and life threatening vasospasm or stroke.
Multiple other medications over the last several years have now been tried for the vasodilators. Each of these classes and results will be discussed in their specific following paragraphs.
With respect to beta blockers, Inderal (Propranolol), Tenormin (Atenolol), Normodyne (Labetolol), Lopressor (Metoprolol) have all been tried. None of these have been significantly effective at vasodilation. However, when using vasodilators, patients will frequently notice waxing and waning of their effectiveness. This is especially noticeable in patients who are beginning to be tapered off their medications due to good responses, and thus cannot tolerate higher doses of vasodilators without developing symptomatic lethargy, hypotension, etc. from the medications. In these patients, Beta blockers have been extremely effective in smoothing out the sympathetic nervous system excitability and variability that may be seen. In my patient population, Inderal (Propranolol) has been most effective. The other medications have not been effective, although probably are useful in blunting any acute response to Nitroglycerin administration from a hypersensitive Nitric Oxide response, if the patient is prone to such a response.
Alpha blockers have been tried. Clonidine has been extremely effective. Hytrin (Terazosin), Ismelin (Guanethidine), Minipress (Prazosin),have been all tried, with less successful results. Cardura (Doxazosin) is still being tried, but initial results are just now coming available. Dibenzyline (Phenoxybenzamine) has also been tried, and appears to be relatively mild, similar in action on the vasospasm as Hytrin (Terazosin).
Angiotensin Converting Enzyme Inhibitors (ACE) inhibitors have been tried including Accupril (Quinapril), Altace (Ramipril), Capoten(Captopril), Lotensin (Benazepril), Monopril (Fosinopril), Prinivil (Lisinopril), Zestril (Lisinopril timed released), Univasc (Moexipril), Vasotec (Elalapril), Cozaar (Losartan). Accupril (Quinapril) has consistently been the most effective. With use of Accupril (Quinapril) and concomitant administration of low dose Nitroglycerin, 1/10th inch once a day to several times a day, most patients may be eventually weaned from the use of oral medications, although I do tend to maintain them on low dose Nitroglycerin in perpetuity, as the inciting cause of the vasospasm usually remains and usually causes redevelopment of symptoms. However, these symptoms and radiological as well as symptomatic vasospasm may be controlled with low dose medication if Accupril (Quinapril) is used initially. The timed release medications such as Zestril (Lisinopril) are extremely effective in part due to increased patient compliance. Although I personally find these two afore-mentioned medications the most helpful, Capoten (Captoptil), Lotensin (Benzepril), Prinivil (Lisinopril) are close second tier medications. The other ACE inhibitors tend to be effective, but a third tier alternative drug. However, as a patient becomes intolerant to the stronger ACE inhibitors, these second and third tier drugs may be very helpful in preventing and controlling the vasospasm without developing intolerance to the medication. Similarly, in less severe cases, these are excellent first line drugs.
Calcium channel blockers have been tried. In the most severe cases, Dynacirc (Isradapine) has been extremely effective. Adalat (Nifedipine) in standard doses and timed release dosages has been helpful but as a second line drug. Cardene (Nicardipine), Nimotop (Nimodopine), Cardizem (Diltiazem), Norvasc (Amlodipine) have been less effective in relieving the vasospasm or in allowing a degree of vascular relaxation sufficient to allow the patient to taper from the medication over time. Sular (Nisoldipine) and Plendil (Felodipine) appears to be slightly milder than Dynacirc (Isradapine) and has been effective in those that could not tolerate Dynacirc. Verapamil in its many manifestations is only rarely used, due to its minimal direct effect on vasodilating the vasculature as documented by Transcranial Doppler or in its ability to affect the outcome of these disorders. Vascor (Bepridil) is just now being tried on some patients. Of course, the general comments concerning ACE inhibitors also apply to these medicines. My first line medications may be too strong for the other physicians’ patient populations if those practices don’t tend to attract as severely impaired individuals. Thus, the second and third tier medications may be better tolerated in less severely affected people, and similarly, as patients are able to taper from medications, they may taper into more mild medications from the same classes as previously were shown to be successful.
Other Vasodilators that have not been previously discussed have also been tried. Hydralazine is effective, but tends to cause significant blood pressure changes in these patients. Interestingly though, Hydralazine tends to improve the morphology of the diastolic flow component dramatically, which, in view of Hydralazine’s effect on arterioles, bolsters the perspective that the diastolic phase of the Transcranial Doppler is a good indicator of downstream runoff. Flolan (Epoprostenol) has not yet been tried, nor has IV Papaverine or Inocor (Amrinone). Reserpine has been extensively used. It can be very effective. It’s initial effect is parasympathomimetic. A later effect is sympatholytic. Its role is that it may be very effectively used as an adjunctive drug especially when patients have difficulty tolerating stronger vasodilators. The dose which initially is most effective of Reserpine frequently needs to be decreased dramatically (generally 50%) approximately 6 weeks into therapy as the sympatholytic activities and other central effects start to become significant.
Antipsychotic agents have also been used. Several of my patients who I will be reporting on later, were psychotic, and responded well to these medications and had significant vasospasm identified
on ultrasound which improved after the administration of medication. Of the antipsychotic, Mellaril (Thioridizine) has not been effective. Thorazine (Chlorpromazine) has been moderately effective. Navane (Thiothixene) has been extremely effective, and Respiradol (Respiradone) has generally improved the patient’s symptoms, but had no significant improvement on ultrasound. It has been less well-tolerated in comparison with Thorazine and Navane. Interestingly enough, most of the patients who were placed on Navane, did not continue to require Navane two to three months after starting the medication, and were able to be weaned from that and had better response to their other vasodilators. In general, Navane was used as a first line drug in patients who had severe elevations of Transcranial Doppler Artery mean flow velocities greater than 1.3, and we would generally expect 50% improvement in the Transcranial Doppler Artery Ultrasound within a half hour of administering Navane by liquid solution. The solution was made by stirring 2 mg of Navane in 4 ounces of water then administered orally. The patients were usually afterwards placed on vasodilators such as ace inhibitors and calcium channel blockers.
The approach used in my clinical practice of over 2,000 patients, is the approach of using vasodilators to treat migraine headache, to cause improvement in closed head injury symptoms, and to treat vasospasm from any cause. This has also been effective in Attention Deficit Disorder (ADD) and multiple other disorders with cerebral ischemia or vasospasm as a component. A partial list of these disorders include Vascular Seizures, Vertigo, Tinnitis, Post Subarachnoid Hemmorhage Vasospasm secondary to both aneurysm rupture or trauma, Stroke, reversal of a chronic stroke penumbra, autism, depression, Post-Traumatic Stress Syndrome, Multiple Sclerosis4, autism, dyslexia, visual disturbances and blindness, Autism, Tourette’s Syndrome, Tics, Tremors, Ataxia and multiple other neurocognitive, neuropsychiatric, and neurological disorders that have vasospasm and ischemia as a common aetiology, systemic disorders with diffuse vascular involvement, i.e. some types of Fibromyalgia and Prinz-Metal Angina may also be treated with this approach. The approach to treatment and results are essentially identical in these cases, with minor variations.
However, 10% of patients placed on antihypertensives will develop peripheral hypotension before the vasospasm is successfully treated. In these patients, their central nervous system vasculature is less responsive to the vasodilators than is their peripheral vasculature. These patients will develop hypotension prior to the central vasospasm being successfuly treated.
Several approaches may be taken to these patients. The physician may use medications that primarily dilate centrally. In these patients, Navane (Thiothixene) and other antipsychotics of that group, have been found to be an extremely effective central vasodilator without causing peripheral blood pressure changes. Adjunctive use of low dose Angiotensin Converting Enzyme Inhibitors, Calcium Channel Blockers, Alpha blockers and/or Nitrates with the use of Navane (Thiothixene) and the other anti-psychotics of that group may result in excellent resolution of vasospasm.
Alternatively, intravenous or intramuscular medications that primarily act centrally can be effective and used in emergency as well as non-emergency situations. Intravenous magnesium, (in our experience, 5 grams slowly infused5 over 1 hour is extemely helpful), I.M. Toradol (Ketorolac) in doses of 90-120 milligrams is also extremely effective with onset of action in approximately 4 minutes (Lower doses are not as effective, however, these higher doses are no longer FDA approved, and thus I now longer use them. The intraveous route of Toradol-Ketorolac probably has a carrier agent which aggravates the vasospasm, as discussed earlier in another section of this article.)
The physician may alternatively use therapeutic approaches to increase the effectiveness of the medical therapy. Techniques that selectively denervate the sympathetics to the brain, as occurs in percutaneous neurolysis or nerve blocks, will result in the blood vessels of the brain responding to the vasodilators in a manner more in synch with that of the peripheral nervous system, thus decreasing the tendency for peripheral hypotension that is sometimes seen with these medications. Alternative mechanisms of decreasing sympathetic nervous system activity, from cervical manipulation that decrease autonomic nervous system activity in the neck, to biofeedback, to treating other causes of sympathetic nervous system hyperactivity, such as chronic pain syndromes, all have their role in specific patients.
At times, these vasodilators may themselves cause a re-occurence of the patient’s symptoms, as all of these medications have many of these symptoms as side effects. Generally, by identifying if the patients symptoms re-occur in consistent relationship to when the medication is taken quickly identifies if the problem is from too much medication or too little medication. Occasionally, one may try a therapeutic challenge. Nitroglycerin, or any other vasodilator, may be used. Nitroglycerin is especially helpful to to its rapid onset of action, and rapid clearing from the body.
A small dose of nitroglycerin may be applied. If the patient’s symptoms improve and stay improved for over 1 hour, the patient is generally undermedicated with vasodilators. If the patient deteriorates, or has a brief improvement, followed by deterioration, he is generally overmedicated. Such brief improvement followed by deterioration can be explained by the understanding that Nitroglycerin is rapidly metabolized into secondary vasodilators. A person over-medicated, which itself can result in vasospasm, may have initial vascular dilation due to the nitroglycerin, which then, as it is metabolized to longer acting vasodilators, actually aggravates the clinical symptoms. Of course, transcranial doppler monitoring, if necessary in association with a nitro challenge, can also generally rapidly answer the clinical questions of over vs. under-medication.
It is important to realize that for centuries we have been treating neurological diseases as though each symptom or symptom complex represented a different disease. Our office has found that many of these diseases represent the same disorder with different manifestations. The cause of the disorder and the treatment of that cause may vary widely. However, the treatment of the patient is the same.
We strongly adovocate searching for any vascular component of any patients neurological disorder, and aggressive treatment of that vascular component. It has been our experience that until the the vascular disorder is reversed, it is impossible to identify the portion of the patient’s neurological problems that are left behind.
1. Ischemia: Loss of sufficient oxygenation to an organ, as may be seen with a loss of blood flow from that required for the health of an organ.
2. We have successfully treated a large number of different diseases with the use of medication that dilates blood vessels leading to the brain.
The results are dramatic and reproducible. Indeed, when these techniques are applied across the country, the practitioners will feel that they have defeated many of these disorders. As I have experience in over 2000 cases of reversing these vascular disorders, I have learned that vasospasm/vascular ischemia is probably not the cause of any of these diseases. Rather, it is the cause of the diseases’ symptoms. In treating these patients, we frequently get dramatic improvements from using the vasodilators or other agents that increase blood flow to the tissue. However, if the medication is stopped, decreased inappropriately, or the underlying disorder goes through an exacerbation, symptoms of vascular ischemia will return. These symptoms are only rarely the same symptoms with which the patient presented. Generally, they are other symptoms somewhere on the continuuam of neurological and psychological changes that accompany ischemia. Thus, those symptoms may range from increased distractability, to behavioral/mood/memory/language/spatial disturbances, to sensorimotor disturbances such as visual/balance/motor problems, on to headache, or, in the most severe cases, stroke, seizure, syncope.
What follows is a partial listing of diseases that have been successfully treated:
In the Psychiatric/Psychological arena:
Depression, Impulsive Rage Disturbances, Irritability, Emotional Lability, Psychosis, Autism, Attention Deficit Disorder and its variants, Memory Loss, Tourette’s Syndrome, Transient Global Amnesia
In the Neurological/Physical arena:
Stroke, Grand Mal Epilepsy, Absence or Petit Mal Epilepsy, Psychomotor Epilepsy, Headache, Closed Head Injury, Post Concussion Syndrome, Vertigo, Ataxia, Tinnitis, Aphasia, Apraxias, Visual Loss, Visual Blurring, Blindness, Stuttering, Vasospasm after Sub-Arachnoid Hemmorhage, Vasospasm after Intracranial surgery not associated with trauma or Sub-Arachnoid Hemmorhage, disturbances of Word substitution and Word Finding, Dyslexia, Photophobia, Hyperaccusis, Tremor, Multiple Sclerosis, Multiple Sclerosis-Like Syndrome, Post Traumatic Stress Syndrome, Vertebrobasilar Insufficiency, Vertigo, Cerebral Palsey, Vertebrogenic Syndrome, Syncope, Multi-Infarct Dementia, “Alzheimer’s” Syndrome, Whiplash Induced Headaches, Headaches in general, TMJ Headaches6 Steroid Induced Migraines, Steroid Induced Psychosis, Fibromyalgia, Prinz-Metal Angina, Neuro-cognitive changes associated with electrical and lightning injuries.
3. The neurocognitive and behavioral disorders run the gamut from severe to mild, Autism, to depression, to mild disturbances of communication, interpretation of others’ communication, and distractability. Although the more severe disorders in this range are easy to identify and recognize, the less severe disturbances result in difficulty with interpersonal relationships, work productivity and output. A common link in the histories, is that most patients will describe variability in their cognitive and emotional abilities. Further, that these changes are frequently associated with stress or pain. This is due to the stress causing increasing vascular constriction, ischemia, and altered mood, personality change, and memory. As the stress or pain response, or any other irritant of the sympathetic nervous system decreases, the personality and mood disorders will lessen. As patients are not always the best historians at identifying these links, the physician needs to be aware and obtain histories from those about the patient. A classic finding in these patients is increased rates of divorce or job changes. In the followup of these patients, attention must be spent looking at these issues of interpersonal and business activity.
Disorders in these areas are frequently related to early ischemia, in my practice from incompletely treated Vasospasm or narrowing of the arteries of the brain. This can be easily confirmed from a repeat ultrasound, computerized EEG, or neuropsychological tests. A classic finding on neuropsychological testing is the cognitive variability identified on testing. Treatment for any remaining vasospasm rapidly improves these disorders.
Patients who are successful in completing treatment in my practice generally show great job and social stability.
4. The case of Multiple Sclerosis is especially instructive for understanding the role of Vasospasm in multiple neurological disorders, as our experience with Multiple Sclerosis highlights that these neurological syndromes are frequently multifactorial. The vascular component can exist in isolation as the cause of the entire disorder in some patients, and in other patients, it may be a concommitant disorder. These cases will be discussed further in future articles, however, an overview of our clinical experience is relevant now.
Virtually all patients with the diagnosis of Multiple Sclerosis referred to me have had Vasospasm on Transcranial Doppler. The diagnosis of Multiple Sclerosis in all cases were confirmed by outside neurologists before referral to me.
Approximately one third of these patients had dramatic improvement, including MRI improvement of placques, with medication to control the vasospasm. None of these patients had relapses as long as they stayed on their vasodilating medications and all abnormalities on TCD were successfully treated and prevented from returning by the use of ongoing monitoring during clinically asymptomatic periods.
A second third suggests that the neurological deficit is a combination of vascular injury and direct attack on the nervous system. These patients, during acute attacks, had significant improvement in neurological functioning with reduction of the vasospasm identified on ultrasound. However, they continued to have new neurological deficits from the new attack on the nervous system. Those deficits required alternative therapies such as steroids to treat ( with respect to steroids, monitoring with TCD is vital, as in some patients, the steroid itself could cause vasospasm. Steroids, of course, have complex and myriad effects on the nervous system, some of their effects may increase neurological functioning and efficiency of activity, thus improving a patient clinically, even as the concommitant vasospasm is aggravating the underlying neurological injury). These patients probably had a degree of autoimmune attack on both the vasculature and the nervous system. The degree of residual dysfunction, which sometimes continued to progress in spite of successful control of the vasospasm in the clinical outbreak, suggests that the autoimmune attack continued on the nervous system. Their clinical course, however, also suggests that the underlying autoimmune attack on the nervous system was aggravated by an ongoing ischemia brought on by a concommitant attack on the blood vessels. It was this vascular aspect of the disease that was altered.
The third group had successful control of the vasospasm, but without significant clinical improvement. The time course and progress of the acute attack continued without any significant clinical change. This suggests that there was a concommitant antibody attack to the blood vessels, as vasospasm was identified on the ultrasounds, but that this vasospasm was not clinically significant.
My experience with these results and clinical cases will be further discussed in future publications.
5. With respect to Intravenous Magnesium, we have found that slow infusions are a potent central vasodilator. Their time of onset generally is after approximately 4 grams have been infused over one hour almost regardless of weight of adult patient. Time course of clinical response varies from hours to one week. However, we have also found that when patients complain of facial flushing and heat, a TCD will show temporary aggravation of the vasospasm. Thus, rates of infusion must be monitored so as not to cause a temporary aggravation of the underlying vasospastic disorder. Apparently Magnesium intravenously acts similarly to all the other vasodilators we have used in that there is a therapeutic window. Underdosage of the individual results in incomplete control of the vascular disorder, and overdosage may result in a transient paradoxical vasoconstriction. This observation has immediate and obvious significance for the Obstetric/Gynecology professions, as Intraveous Magnesium is a routine therapy for Toxesimia/Pre-Eclampsia, a condition where there is severe vasoconstriction of the arteries which may lead to stroke, seizure, or death of the child or mother. Clinical case reports will be reported at a later date, but the preliminary findings are so important that they need to be considered and reproduced by others immediately.
6. Temperomandibular headaches (TMJ) are improved to the degree that their is a reversible vascular headache seperated from but triggered by the TMJ disorder. However, when the TMJ is severe, we frequently can not get significant resolution of the headache using only vasodilator approaches unless the TMJ syndrome is itself successfuly treated. In the respect that a severe injury can overwhelm our abilities to control the vasospasm, TMJ is no different from other severe injuries such as disk or joint injuries which may result in such severe sympathetic nervous system response that we cannot control the secondary vasospasm.
GLOSSARY OF MORPHOLOGICAL CHANGES OF TRANSCRANIAL DOPPLER
Examples of Normal and Abnormal Transcranial Dopplers by Morphology, in our experience, these are arranged from normal to progressively abnormal.
Normal Transcranial Doppler Morphology
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Example of Abnormal Transcranial Doppler due to elevation of the diastolic run-off phase throughout diastole with slowly diminishing flow velocities to end diastole. No elevation of Mean Flow Velocity is seen. Highlighting of the abnormality is done in dotted lines.
Abnormal Transcranial Doppler Showing Abnormal Spike with Systole( frequently seen in rigid, non-compliant vasculature), as well as abnormally elevated and prolonged diastolic phase run-off.
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Abnormal Transcranial Doppler with elevated with Flow Velocities which slowly diminish throughout the diastolic phase to End Diastole (overall Mean Flow Velocity is elevated)
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Abnormal Transcranial Doppler due to blunting and rounding of the systolic upstroke, a finding frequently found in disseminated vascular disease, as well as in chronic vasospastic disease. This blunting and rounding of the systolic phase is probably due to proximal constriction increasing resistance to flow, thus causing a delay in the systolic phase. The downstream diastolic run-off phase shows only minimal abnormalities throughout diastole in this case. At times, this rounding and blunting of the systolic phase is seen in the final stages of resolution of the vasospasm.
Thus, this finding may be seen as a late finding in the treatment of chronic vasospasm, or in severe untreated vasospasm. In the more chronic case, the envelope is generally less well defined and has a somewhat shaggy appearance. In the case of resolving vasospasm under treatment, the medications act first on the diastolic run-off phase of the ultrasound; thus the smaller arterioles which are more sensitive to the vasodilator will dilate first, giving improved run-off. In these cases, the envelope has a less shaggy appearance due to greater coherence of the flow velocities. In both chronic and resolving vasospasm, this blunting of the upstroke of the systolic phase probably represents more proximal vasoconstriction with downstream runoff sufficient for the degree of blood flow traveling through the narrowed proximal artery.
Rounding of the systolic phase more typical of chronic disease (Although poorly exemplified here due to conversion of this file into a compressed GIF file for the Internet)
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Second example of blunting and rounding of systolic upstroke of spectrum of Transcranial Doppler seen in a patient responding well to vasodilators.
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Example of Unidentified Bright Objects in case of Severe Vasospasm. These Unidentified Bright Objects have previously been reported in cases of embolism. We , also, frequently seen these during severe vasospastic attacks. They are halted with standard vasodilating medications. This patient was a young female with normal carotid/cardiac echocardiograms and Reflex Sympathetic Dystrophy from a neck injury. During sympathetic attacks, these UBOâ€™s were frequently identified. Due to the quality of compression, the UBO’s are not well represented by these pictures.
copyright MedForum and Lifelines Medical Journal 1997
copyright MedForum and Lifelines Medical Journal 1997
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