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Integration of the Evaluation and Management of the Transient Closed Head Injury Patient: Some Directions

Vernon M Neppe MD, PhD, FRCPC, FFPsych, MMed, DipABPN,
Director, Pacific Neuropsychiatric Institute, Seattle, WA
Adj. Professor of Psychiatry , St Louis University, St Louis, MO

See the publication which contains this article in full (reprinted by kind consent of the Pacific Neuropsychiatric Institute)
Neppe, VM.  Integration of the Evaluation and Management of the Transient Closed Head Injury Patient: Some Directions.
Chapter 19, Pages 421-450.  In Varney, N. and Roberts, R. (editors)  Evaluation and Treatment of Mild Traumatic Brain Injury.
Published by Erlbaum and Associates, Mahweh, NJ. 1999.

Table of Contents

  • Background to Assessment of the CHIT 
  • Introduction 
  • Non-Pharmacologic Approaches 
  • Pharmacologic Interventions 
  • Pharmacologic Preliminaries 
  • Neuromodulation Options 
  • Anticonvulsant Options 
  • Seizures in Head Injury 
  • Kindling and Chindling 
  • Anticonvulsant Prescription 
  • The Biological Sleep Cycle Disruption 
  • Management of Depression and Mood Disorder 
  • More Uncommon Pharmacologic Options for the CHIT Patient 
  • Conclusion 
  • See also Transient Closed Head Injury Assessment


    We have defined the "closed head injury syndrome of transient kind" (CHIT) as having several subtypes: a physiological brain injury of the post concussional dimension (PCCHITs), a psychological dysfunction of post-traumatic kind (PTCHITs), a focal residual kind (FRCHITs) or combinations mixed with these (MCHITs). Further, there is a synergistic physical, cognitive and psychological synergism across the post traumatic functional syndrome and legitimate brain injury and predisposing factors and degrees of physiological brain reserve may determine exact manifestations of a CHIT. (Neppe and Goodwin, In Press)

    We have seen how "minor" CHI is often not minor. The misnomer of mild often is linked with significant and brief, or no impairments of consciousness may be associated with significant residua of the CHIT. Some patients may manifest pathoplastic compensations less with pre-existing conditions such that the symptoms of the CHIT may relate to the straw that broke the camel's back. Additionally, the actual pathogenetic changes in CHITs may manifest in both focal and generalized forms. (Neppe and Goodwin, In Press)

    We have demonstrated how time based evaluations of comprehensive kind may be the most valuable way of monitoring of the headache, dizziness, concentration, myalgic pains, memory disturbance and sleep disturbance and specific complications including seizure disorders, atypical spells and fibromyalgia that may follow CHITs. The neuropsychiatric evaluation is not a single interview over forty minutes or an hour. It cannot be done in one interview: it is too complex and, moreover, the time based evaluation allows a film strip view in which the whole system, all the biopsychofamiliosociocultural elements, must be taken into account. (Neppe and Goodwin, In Press)

    The sequence of such a basic exam involves outside sources of history and information, demographics analysis, a detailed main complaint with injury information, relevant past psychiatric and neurologic history including any other injuries and any links with lawsuits, a detailed pharmacologic history including doses, duration, combinations, responsiveness, side-effects, a history of abuse of recreational drugs, basic habits, a detailed computerized history of social and medical facets, psychological and personality evaluations, obtaining of collateral information, and detailed neurologic, psychiatric, mental status, and neuropsychiatric cerebral cortical evaluations. Furthermore, specialized testing is then done. All this information is then elaborated and examined producing diagnoses using a multiaxial framework of both neurologic and psychiatric kind. Consequently, management of the patient with a CHIT requires comprehensive time based evaluations and significant planning. Such handling is both pharmacological and non-pharmacological. (Neppe and Goodwin, In Press)

    While we have always had pharmacologic agents that had behavioral effects on brain injured patients, it was only with the investigations associated with modern pharmacology that we began to understand the neurotransmitter systems affected by these agents and particularly began to notice that some of these neurotransmitter systems appeared to be disturbed in various mental illnesses. These studies into the pathophysiology of head injury have extended, inter alia, to electrophysiologic measures of sleep, evoked potentials, reaction times, and ambulatory electroencephalography . They have further This chapter is not intended to be complete. It simply highlights several areas of management in the CHIT patient with the awareness that management involves two components : further investigations as necessary and pharmacologic and other therapeutic interventions. 


    Four levels of management exist in the CHIT patient, namely further investigations, cognitive rehabilitation, non-pharmacologic approaches and pharmacologic interventions. This chapter focuses on the last - the pharmacologic - but all four areas are critical.


    After the longitudinal time-based initial evaluation, additional tests are based on the specific evaluation. Early on such tests as MRI, CT and routine sleep and wake electroencephalography plus supporting blood tests should be performed as indicated in the previous section (Neppe and Goodwin, in press). Changes in behavior should be carefully monitored as accurate diagnosis and evaluation is a key to appropriate management and further tests done as indicated.


    Cognitive rehabilitation is exceedingly important. The potential use of computers in this regard is an area in its infancy that will rapidly grow over the next decade. This is also not specifically focussed on in this chapter.

    NON-PHARMACOLOGIC APPROACHES: Basic guidelines and habits

    The following guidelines have been prepared for the CHIT patient.

    Three regular meals per day are essential Vegetables and fruit are particularly useful. Avoid highly refined sugars such as candies Consideration of supplementation with Vitamins such as E, D, B6 and C or a complex of multivitamins is warranted. Even Vitamins can be toxic in high doses so appropriate dosing is important. Additionally, drug interactions can occur given the fat solubility of such vitamins as A, E and D. Avoid saccharins and nutrasweet until it is established that no specific behavioral effects occur correlating with these. Significant water intake is useful (hence the value of water filters) Plenty of exercise regulated appropriately by the primary care physician is valuable - graded aerobic elements

    a. Cut down on any CAFFEINATED beverage consumption. Because of the presence of symptomatology which may in part be attributed to the caffeine intake, we recommend the patient to taper totally off beverages - coffee tea cola drinks - at the rate of 1 cup per day. Decaffeinated beverages can be taken as needed instead. Withdrawal effects such as caffeine withdrawal headache can be managed with acetaminophen and a slower taper of the caffeine.

    b. Cut down on any ALCOHOL. Besides direct effects, this will commonly interact with medications at one or more of four levels: absorption, altered metabolism, modified responsiveness at receptor levels and behavioral effects. Unless there are specific reasons, such as seizures triggered by a tot of wine, previous or current alcohol or drug difficulties or such predisposition, aggression or bizarre previous reactions to alcohol or driving, the occasional small amount of low potency alcohol (e.g. beer) or medium potency (e.g. wine) is acceptable.

    c. Clearly the use of any PLEASURE DRUGS of abuse should be avoided.

    d. Cut down on SMOKING. This can also be done using a slow taper. The availability of either Nicorette gum or Habitrol is a useful usable adjunct in this regard. Smoking withdrawal is commonly associated with weight gain and I have recommended that noncalorific fluids such as water be used instead; appropriate solids would be lentils, carrots and tomatoes which can be eaten instead. Moreover, changes in cigarette habit may result in different prescription needs because drug interactions or hepatic metabolism may change.

    a. ALLERGY: An air filter in home may be useful particularly in the context of any allergy history.

    b. BED AND SLEEP: The mattress should be good and firm; it should be turned regularly; The pillow should be comfortable; a neck pillow should be used in the event of neck pain. Any snoring should be taken seriously and this associated with any other features of possible sleep apnea, such as day time fatigue or periods of not breathing noted by others handled. The value of adequate temperature in the room - neither hot nor cold cannot be over-estimated. During winter, if greater fatigue or seasonal variations of mood arise, the use of a simple timer switch to create artificial light may be valuable; failing this more appropriate light therapy may be used, if necessary and severe enough.

    c. NECK A nodule vibrator or equivalent for the neck in the event of any neck pain may be useful.

    a. MEMORY: Most so-called memory deficits have a significant functional component frequently relating to the non-specific symptoms of poor concentration. Valuable is the habit of recording information in a note-book to be carried around everywhere. This should include a list of To Do items and an address book. A cheap watch with multiple alarms is useful to ensure compliance with medications and relevant arrangements

    b. SPEECH: The use of computerized software (such as the program Word Foundry by Nordic software) may be useful for receptive or executive level mild aphasia. If the initial evaluation is suggestive of speech pathology, subtle elements could have been missed such as specific reading disability and an educational evaluation should be performed.

    c. PSYCHOLOGICAL: Express anger by using a punch bag. Exercise may be useful Loneliness may be alleviated by joining a social club. Write notes to self to express distress

    d. DRIVING: The operation of any motor or any other vehicle is always controversial. Most medications sedate somewhat and even those that do not may cause paradoxic reactions. On the other hand, certain conditions such as anxiety, day-time sleepiness, seizures, poor concentration or memory disturbance aggravate driving risk and the treatment may be assisting these problems. Extreme care should be used when driving, and even when it is deemed safe to drive short distances in familiar areas, it may be unsafe on longer or unfamiliar drives. Driving should be avoided in the event of doubt as to safety to drive not only on behalf of the patient but the family. Driving a car is always the ultimate responsibility of the individual driving it. The physician can advise in cases of uncertainty - frequently, medication control is safer than the untreated underlying condition, but any sedation or slowed reaction times or impaired consciousness or sleep, visual or memory impairment is a good reason not to drive.

    e. PSYCHOTHERAPEUTIC SUPPORT Supportive psychotherapy with an appropriately trained therapist is useful. This should be directed at support with regard to current problems as well as allowing the patient a smoother transition as readjustments back to a healthy core occurs. Depth therapeutic probing, uncovering many layers of the patients psyche should be approached only with extreme caution as this may lead to further decompensation.

    f. BEHAVIORAL ELEMENTS: Access to a firearm, in the context of significant psychopathology linked with the CHIT, is dangerous. This should be avoided if at all possible.

    g. FOLLOW UP The patient should always have a regular follow-up primary care physician to handle any acute problems.


    Pharmacologic interventions are dependent on diagnostic evaluation. The four major intervention groups are:
    1. The azapirone, buspirone, technically an anxioselective agent, is the most versatile and possibly the safest of all medications in the CHIT. However, because of the organicity, even buspirone is sometimes associated with paradoxic reactions, such as irritability instead of anti-aggressive effects.
    2. The use of anticonvulsant medication for focal residual CHITs is critical at times.
    3. Assistance with disruption of the biological cycle of sleep.
    4. Antidepressant medication is commonly used to manage the depression and also the pain syndromes.
    More uncommon interventions are linked with:
    1. Beta-adrenergic blocking agents like nadolol and propranolol which are sometimes useful in situations of autonomic instability with significant somatization.
    2. Occasional psychostimulant medication is used for the apathy or for an attention deficit disorder like condition or for profound sleepiness.
    3. Use of antipsychotic medication such as perphenazine.
    4. Supplements such as minerals , vitamins and the various fatty acids are all speculative approaches generally characterized by the absence of specific medical prescription.
    Finally, Analgesics and muscle relaxants may be necessary to treat pain syndromes. This is not specifically dealt with below.

    Highlights of use of these various medications and the conditions in which they should be considered are outlined below with emphasis on specific practical clinical approaches and needs.

    One should take only the medication that is needed, the patient should be informed about the prescription medications and compliance with treatment is essential.

    Prior to medicating with extras, one approach is often to establish that a drug is indeed doing more good than harm. Tapering or cessation of any medication prescribed in a CHIT is a reasonable approach when side-effects are significant or there is a lack of therapeutic effects

    Whenever prescribed, the patient should ensure that the pharmacist dispensing the prescription give a package insert which can be read to ensure familiarity with side-effects. However, this should be in the context of appropriate medical education by the prescribing physician and the pharmacist lest the patient distort side-effects and therapeutic indication which in the CHIT context is frequently outside labeling. It is good practice for physicians to develop specific schedules in this regard prioritizing relevant side-effects and dosing difficulties. Frequently, side-effects pertaining to weight gain on such medications as valproate, tricyclic antidepressants and neuroleptics are not listed in such inserts. Some effects listed are very uncommon or may not necessarily be associated with the medication specifically but may have been coincidental. The patient should feel free to further discuss these with the physician.

    Compliance with medication and cognitive rehabilitation is critical. Because of memory impairments and amotivation, it is often necessary to assist with compliance in the CHIT patient. Medication compliance may be increased by:

    1. buying a cheap alarm watch with if necessary multiple alarms.
    2. Mediset or tablet dispensers and medication being prepared once per week in these dispenser medisets.
    3. One regular pattern is to take medication at specific times linked with actions. Patterns of regularity which is individually determined such as breakfast, lunch and dinner are useful.
    4. Take medication with water and avoid chocolate milk or cola drinks or beverages for about half and hour before and after. Alterations in absorption pattern may otherwise result.
    5. If taking nonprescribed tablets such as minerals or vitamins or health store medications then preferably take them at a different time so that absorption interactions will be diminished.
    6. Consistency is important.
    7. If a dose is missed, in general, take that dose as soon as the error is discovered - this may mean taking one double dose. If several doses have been missed, take one double dose with the next dose, then with the following dose a dose and a half, then regular prescription.



      Unless specifically indicated, medications are generally not necessary in a CHIT. However, even if they may not be necessary at one point, these ideas may serve as a guide for future management of individual patients. Treatment is commonly based on symptom alleviation although chemical regulation with buspirone or putting out fires with anticonvulsants is sometimes based on treating the underlying cause.

      The four major groups of treatment (neuromodulation, anticonvulsants, sleep disruption, antidepressants) and the specific conditions linked with these medications

      Post traumatic head injury characterologic changes and Personality Disorders and Anxiety Disorders Following transient traumatic head injury, a range of central nervous system dysfunctions may ultimately influence the behavior we site as characterological disturbances. Organic links (from diverse etiologies) have been noted particularly in antisocial personality by Lewis and Bella (1976), Robins (1966), Thomas and Chess (1977l, and Tucker and Pincus (1980). Usually these correlate with antisocial behavior and delinquency that relates to EEG abnormalities, delayed reaction times, and seizure disorders. (Tucker, Neppe 1988) The heterogeneous and poorly validated condition of borderline personality disorder with fluctuations in affect, intensity of experience, irritability, frequent suicidal behaviors, aberrant behavior spells, and brief psychotic features with total recovery all suggest some temporolimbic instability. (Tucker, Neppe 1988, 1994); (Tucker et al 1986)

      Anxiety is a ubiquitous psychiatric symptom. Episodes of anxiety, particularly so-called "panic attacks" may correlate in our experience with complex partial seizures. Such events were recognized by Hughlings Jackson last century. (Neppe, 1984A) Most anxieties with head injuries are likely to be on the psychological side not due to brain injury however.

      BUSPIRONE (BUSPAR) medication. This is a prime drug for the patient with a CHIT because of its versatility and safety. The buspirone can be used for the approved usage of relieving anxiety / mixed anxiety depression in the post-traumatic CHIT. In this instance, the post-synaptic serotonin 1A partial agonist effect comes into play. The usual dose for anxiety is 10 mg t.i.d., for mixed-anxiety depression is 15 mg t.i.d. (Neppe, 1990 A, 1989A, 1993A) However, it should alleviate the following symptoms  sometimes linked with anxiety which are frequently relate to post-concussional phenomena of the CHIT: concentration disturbance and also the spectrum of agitation, irritability, frustration, anger, aggression (where no FDA approved drugs exist): Two dose levels of dosage are useful - low e.g. 5 mg t.i.d. which probably reflects autoreceptor raphe serotonergic nuclei effects; and high for considerable agitation and co-existing other symptoms e.g. 20 mg t.i.d. probably reflecting a predominantly serotonin 1A weak agonist effect. The low dose is based on the uncontrolled work of Neppe on non-organic patients and Ratey on mental retardates, the higher dose on Neppe's research. In many patients, we suggest initiating dosage at 5 mg t.i.d. built up gradually by increasing by 5 mg every 3 days to a initial aim level of 60 mg per day: if the patient develops non-vertiginous dizziness then drop the dose by 5 mg per day and continue the taper of dose until no dizziness occurs. Additionally, many CHIT patients reveal a predisposition towards obsessionality . Doses of e.g. 20mg t.i.d. probably reflect a predominantly serotonin 1A weak agonist effect and could be useful here - the only approved drugs for obsessive compulsive disorder - Clomipramine (Anafranil) and SSRI drugs like fluoxetine (Prozac) often have significant side-effects in this population. Important relevant side-effects are:

      1. nonvertiginous dizziness - if this occurs the patient could cut down the dose by 5 mg per day, the patient should contact the treating physician and continue the dose at this lower level without continuing to build up the dose at that time.
      2. nausea - this suggests that the medication should be taken with mealtimes - breakfast, lunch and dinner.
      3. headache and restlessness.
      4. the occasional paradoxic accentuation of anger or confusion in the organic CHIT patient - usually an indication that anticonvulsant is necessary.

      Seizure Disorders
      A person is only epileptic when he has seizures recurrently. An epileptic seizure involves paroxysmal cerebral neuronal firing which may or may not produce disturbed consciousness and / or other perceptual or motor alterations (Neppe, 1988A, B). The most classical and common epileptic seizures are of the "grand mal" or generalized "tonic - clonic" kind. These usually involve relatively short (10-30 seconds) tonic movements with marked extension / flexion of muscles but no shaking and then a longer (15-60 sec) clonic tonic manifesting as rhythmic muscle group shaking. These movements may be associated with a phase of laryngeal stridor due to tonic muscles manifesting as a high pitched scream sound. Urinary and occasionally fecal incontinence may occur due to sphincteric change and the seizures are almost invariably followed by headache, sleepiness and / or confusion. When preceded by perceptual, autonomic, affective or cognitive alterations such seizures are secondarily generalized, as opposed to no original locus of firing producing focal features prior to the tonic clonic movements (generalized from the start) (Neppe, 1982 A ). The different epileptic seizures are classified in Table 1.

      Seizures or other paroxysmal neurobehavioral disturbances which may not qualify as seizures because the actual phenomena are not proven to be seizures are not insignificant post-traumatically. Until all variants are measured it would be difficult to estimate exact incidence. This is particularly so in the context of transient closed head injury. (CHIT) There is a dichotomy of the possibly 90% of epileptics who constitute the epilepsy standard patient who have no more psychopathology than the average patient and the epilepsy plus patient - a minority of epilepsy patients having behavioral or psychiatric abnormalities (Neppe, Tucker 1992). Seizure disorders present with a high incidence of behavioral disturbance, which may initially be interpreted as psychiatric in origin (Neppe, Tucker, 1989, 1994). Many of these relate to the temporal lobe of the brain. The features of temporal lobe epilepsy are so varied and so protean that it is necessary to classify them. Neppe has suggested the term "possible temporal lobe symptoms" (PTLSs) for this (Neppe, 1983 A). These are features which can be induced by stimulating areas of the temporal lobe during neurosurgery. These symptoms only become specific symptoms of temporal lobe dysfunction if their occurrence is validated empirically during a seizure - either through observation or by the electroencephalogram (hence the word "possible" in possible temporal lobe seizures) ( Table 2 ) (Neppe, 1983 B). Using a phenomenological analysis, Neppe was able to demonstrate that the symptom of deja vu commonly regarded as symptomatic of temporal lobe epilepsy indeed had a very special phenomenologic quality in patients with temporal lobe epilepsy (Neppe, 1983 A, 1983C ). This involves its association with post-ictal features such as sleepiness, headache and clouded consciousness and its link in time with these features. This association provides an excellent clue to the existence of temporal lobe epilepsy. Deja vu is a normal phenomenon occurring in 70 percent of the population and unless such phenomenological detail is obtained, patients' symptomatology may be misinterpreted. Neppe has similarly done such a study with olfactory hallucinations (Neppe, 1983 B, D, 1982 B). A specific type of temporal lobe epilepsy olfactory hallucination could not be demonstrated although there were suggestive features (Neppe, 1984B). A major message, therefore, may be the relevance of adequately assessing the symptomatology of patients presenting with epilepsy. It may be that this is a direction as relevant as electroencephalographic monitoring (Neppe, 1993 B).

      Theoretical biases: Kindling and Chindling
      Kindling may be relevant in head injury. Generally several events would be required to trigger such a phenomenon but CHIT theoretically may the straw that broke the camel's back. We discuss kindling briefly below.

      Kindling involves the progression of increasingly severe seizure manifestations in response to electrical stimuli of various areas of the brain such as the hippocampus, amygdala, pyriform cortex, or basal ganglia. Such stimulation is initially sub-threshold, but becomes threshold when administered repetitively. These sub-threshold changes, which have been demonstrated in numerous animal species, at times manifest with behavioral changes sometimes preceding the motor seizures (Neppe, 1985A,B,C). Neppe recognized that there are distinct biochemical and other differences between so-called electrical kindling and the chemical induction of the process and so developed the term chindling for the chemical induction of increasingly severe seizure manifestations in response to general chemical stimuli (Neppe, 1989 B).

      Kindling is increasingly difficult to induce with the added degrees of encephalization in primates. If, indeed, the kindling phenomenon occurs in man, it would probably take many years. There is indirect evidence for its occurrence in the development of mirror foci, generalization of seizures, the alcohol withdrawal paradigm, and possibly paradigms of response pertaining to nonresponsive psychosis (Tucker, Neppe, 1988, 1991). However, kindling has become a very useful theoretical concept to rationalize interventions pertaining to adjunctive drugs, particularly anticonvulsants. Whether or not kindling is shown to be an artifact or not is probably not of vital importance, for its role may be as a stimulant to further research.

      The preferential anticonvulsants in this instance are not necessarily for a seizure indication, per se. The subpopulation of CHIT being treated is the focal residual group. They may manifest with frank post-traumatic seizures, however, they may have atypical spells manifesting as the various kinds of episodic events that we have called paroxysmal neurobehavioral disorder (PND). Diagnosis is based clinically, on EEG and on anticonvulsant responsiveness.

      The management of epileptics presenting with behavior disturbance is closely linked to the discussion of epilepsy in relation to psychopathology. The heterogeneity of such conditions implies a heterogeneity of management which is patient based and individually tailored (Neppe, 1988).

      The most important single principle is anticonvulsant monotherapy. It has been well demonstrated that the degree of seizure control is not increased by increasing the number of anticonvulsant medications. (Neppe, Tucker 1988 A, B) It is more important to achieve adequate anticonvulsant dosage and therapeutic ranges on blood levels are often helpful indicators. However, the object should be to adequately control all the patient's seizures and the choice of anticonvulsant is equally important. Management of patients with seizure disorders involves primarily appropriate use of anticonvulsants (Neppe, Tucker, 1988B). In addition, counseling and the various aspects of psychosocial support, allowing the patient to live as normal a life as possible, and to be supported within the framework of the environment, is also important.

      a. CARBAMAZEPINE (Tegretol) is the primary drug in this group for the CHIT indication as it seems to have a specific psychotropic effect. We use it predominantly in the context of temporal lobe phenomena. It should not to be generically substituted (Neppe et al, 1988C ). The carbamazepine in this instance can be used for the approved usage of relieving seizure disorders or any incidental neuralgia and sometimes fibromyalgia (unapproved and unproven). In seizures, the anticonvulsant effect comes into play. The usual dose for seizures are 200-400 mg t.i.d. or q.i.d. based on monitoring serum levels to 8-12 ug/ 100 ml and clinical responsiveness and we have found usually slightly lower doses to be adequate in atypical spells, PND and temporal lobe dysfunction e.g. 200 mg tid.

      Carbamazepine should alleviate the following symptoms which are not FDA approved (and no FDA approved drugs exist): agitation, irritability, frustration, anger, aggression, mood lability, temporal lobe symptomatology: The dose levels are probably in the low therapeutic anticonvulsant range e.g. 6-9 ug/ 100 ml and frequently correspond with an initial target dose of 200 mg t.i.d. The low dose is based on the double blind controlled work of Neppe on patients with EEG temporal lobe abnormalities and refractory psychosis with hostility and a follow-up retrospective chart review on hostile atypical psychotics (Neppe and Bowman, 1991) in which the EEG was normal. The mechanism may be via kindling or chindling and episodic phenomena respond best (Neppe, 1990 B).

      Generally, a starting dose of 100 mg bid build up by 100 mg every three days to an initial target dose of 200 mg t.i.d. Important side-effects relevant for the patient include:

      1. Signs of neurotoxicity : Dizziness, sedation, diplopia and nausea. Each of these symptoms may reflect toxicity so that consideration can be given to one dose being held and the dose dropped by 100 mg per day pending a blood level if necessary.
      2. Allergy: Usually a rash - possibly in as many as one in eight patients - occurs; far less commonly and more seriously a sore throat, fever or mouth ulceration may happen: The patient should stop the medication pending discussion with the treating physician to establish if the reaction is drug related.
      3. Extremely rare is the occurrence of bone-marrow depression which is an idiosyncratic reaction. There appears to be no correlation of the frequent and expected drop in white cell count with this or other immunologic infection predisposition.
      4. Tegretol induces enzymes and may impair control of conception by oral contraceptives. The usual practice has been to increase the OC dose slightly if not contra-indicated for any reason but safer is to add a second contraceptive method as well.
      Prior to beginning the carbamazepine treatment, the following baseline blood tests should be performed: Complete blood count including differential cell count with optional platelet and reticulocyte count. Hepatic enzymes including Gamma Glutamyl Transferase. Electrolytes. At subsequent visits, the carbamazepine levels can be measured and after establishing a new baseline the CBC and GGT can be monitored as necessary. Folate, a B vitamin, supplementation is often necessary based on possible subclinical deficiency induced by carbamazepine which induces hepatic enzymes - folate is a co-enzyme in this cycle. Doses of 5 mg daily are recommended. Calcium supplementation e.g. as gluconate is also relevant sometimes. One mechanism may be carbamazepine enzyme induction producing subclinical Vitamin D deficiency particularly in a cloudy climate.

      b. Other anticonvulsant options are briefly outlined below:

      b. 1. PHENYTOIN (DILANTIN) Adequate control of seizures with only occasional episodes suggesting maintaining this drug. However, high therapeutic levels e.g. 20 ug/ ml are associated with significantly more cognitive side-effects than lower levels. Rigidity, slowed thinking, irritability, sedation, poor psychomotor control and responsiveness are examples. Consequently, lower doses may be more logical even with adjunctive second anticonvulsant, if necessary. Folate and Vitamin D and Calcium supplementation should be considered. The initial aim dosage is 300 mg daily , as a TID or QD dosing. Phenytoin can be given intravenously if necessary. Important side-effects relevant for the patient include:

      1. The change to zero order pharmacokinetics with potential toxicity with slight dose alterations or other drugs added.
      2. The gum hyperplasia is a somewhat disabling long-term effect that is extremely common.
      3. Allergic reactions include rash commonly, neurotoxicity frequently and very rarely bone-marrow phenomena.
      4. Potent enzyme induction with raised hepatic enzymes produces common drug interactions.
      b.2. DIVALPROEX SODIUM (DEPAKOTE). Initiation of DIVALPROEX SODIUM (also called Valproate) (DEPAKOTE - not a generic) may be useful particularly with residual focal frontal lobe phenomena. The Valproate has an approved usage of relieving seizure disorders and for prophylaxis of bipolar illness and for headache prophylaxis. However, it could alleviate the following symptoms which are not FDA approved: agitation, irritability, frustration, anger, aggression, mood lability, temporal lobe symptomatology (no FDA approved drugs exist) but there is limited clinical use in these areas because frequently there is limited effectiveness. A starting dose of 250 mg t.i.d. is suggested. The usual dose for seizures are 250-1000 mg t.i.d. or q.i.d. based on clinical responsiveness mainly but also -far less reliable with valproate - monitoring of serum levels to 70-100 ug/ 100 ml. For non-approved uses slightly lower doses e.g. 250 mg-500 mg t.i.d. or q.i.d. with similar blood levels to seizures may be appropriate. Whether the mechanism then is anticonvulsant or psychotropic is unknown.

      A major advantage of valproate is it is generally well tolerated with few side-effects and less sedative than carbamazepine. Important side-effects relevant for the patient include:

      1. Nausea is common: give with meals.
      2. Dizziness, sedation and diplopia but these are uncommon. Each of these symptoms may reflect toxicity so that consideration can be given to one dose being held and the dose dropped by 250 mg per day pending a blood level if necessary. Supplemental carnitine has been suggested both to prevent hepatotoxicity and diminish any cognitive side-effects. Dosing is disputed but 500 mg qd may be reasonable.
      3. Allergy is rare.
      4. Extremely rare is the occurrence of hepatotoxicity. There appears to be a correlation with anticonvulsant polytherapy in infants and in adults the drug should be safe.
      5. Most psychotropics will push up the Valproate level and it will do likewise. Carbamazepine may lower it. Valproate does not induce enzymes.
      6. Many patients complain of weight gain which may be the most significant common side-effect and reason for discontinuation.
      Prior to beginning the Valproate treatment, the following baseline blood tests should be performed:
      • Complete blood count including differential cell count with optional platelet and reticulocyte count.
      • Hepatic enzymes including Gamma Glutamyl Transferase, Bilirubin, Prothrombin.
      • Electrolytes.
      • At subsequent visits, the valproate levels can be measured and after establishing a new baseline the CBC and GGT can be monitored as necessary.
      b. 3. GABAPENTIN (NEURONTIN) This new anticonvulsant has the advantage of low toxicity, low range of side-effects and no known drug interactions. Serum levels are not helpful for clinical practice as they are non-correlative with therapeutic range or toxicity and they are, in general, unavailable. Technically gabapentin is an adjunctive anticonvulsant, but it may be tried in monotherapy for specific symptoms. Doses of 100 mg t.i.d. are low average although 20% get sedated so start low 100 mg daily building by 100 mg QOD till better control e.g. 300 mg t.i.d.

      b.4. LAMOTRIGINE (LAMICTAL) This new anticonvulsant in the United States had been marketed in numerous countries before that. It has remarkable effects on some although in our experience patients may initially become paradoxically worse with each increase in dose. Like gabapentin, serum levels are unnecessary and unavailable. Technically, it too is an adjunctive anticonvulsant, but it may be tried in monotherapy for specific symptoms. Doses of 25 mg daily built up to 100-200 mg bid over several weeks are average.

      b.5. TOPIRAMATE (TOPIMAX) and TIAGABINE (GABATRIL) These are new anticonvulsants in the United States Tiagabine marketed October 1997). Topiramate comes in 25 mg, 100 mg and 200 mg sizes. Begin with 25 mg bid and build if necessary to up to 400 mg daily. Tiagabine has small milligram sizes with the starting dosage of about 4 mg daily and the usual dosage of 12 through 40 mg per day. Both drugs are useful as adjunctive therapy in patients whose seizures are uncontrolled on monotherapy particularly in partial seizures. Side-effects for both are rather typical for anticonvulsants namely fatigue and psychomotor impairments.

      One of the most common complaints after CHIT is sleep disturbance which may take months or years to fully improve. Many such complaints may be psychiatrically linked, however, some may have biological bases, linked with the conditions above. Sleep disorders are among the most fundamental of all psychiatric disorders, and certain psychiatric illnesses may well have a very profound base with regard to sleep disturbance. For example, a diagnosis of mania may be nearly impossible without a profound decrease in total sleep time and, in fact, most manics have a period of at least 36 hours where they do not sleep at all and during which they do not feel fatigued (Tucker, Neppe, 1988) Similarly, a shift with phase advance and a decreased latency to rapid eye movement sleep is characteristic of a biological depression. Another common symptom in this condition is terminal insomnia - early morning waking. This may or may not be correlated with this phase advancement as the two have not been investigated (Tucker, Neppe, 1988).

      Sleep disturbance is of profound importance in the CHIT but may reflect underlying affective disorder or personality. Many patients with profound degrees of antisocial personality give a history of sleep disturbance involving paroxysmal wakenings since childhood. Many brain impaired individuals may have periods during which they nap during the day.

      HYPNOTICS: When sleep is impaired significantly hypnotics may be considered. Options include zolpidem (FDA approved), trazodone (approved as antidepressant but commonly used) and melatonin (non-prescription hormone)

      a. ZOLPIDEM TARTRATE (AMBIEN) medication. This is a imidazopyridine nonbenzodiazepine hypnotic with no apparent dependence, and normalization of sleep cycles with extensive European experience (5 mg pink or 10 mg white tabs - breakable). It acts at the omega 1 sites of GABA - a receptor preferentially. It is FDA indicated for short-term management of insomnia. It has rapid onset, and short half life (2-3 hours).

      b. TRAZODONE (DESYREL) medication. Trazodone is marketed as an antidepressant: it does not have anticholinergic side-effects and has little cardiotoxicity. In sub-antidepressant doses such as 50-100 mg, it is frequently used as a hypnotic because it is sedative with little carry-over to the next day and has excellent physiological effects on slow wave sleep. Patients should be warned that it may drop blood pressure and induce tachycardia - hence they should go to bed after taking it until they know what effects it has on them. In males there is a rare side-effect of priapism (1 in 8000 males) which can usually effectively be treated with pseudo-ephedrine hydrochloride and immediately packing the penis with ice.

      c. MELATONIN: Given the biological sleep disturbance component and disturbances in diurnal rhythms, Melatonin is a non-prescribed option left to the patient's choice. The following key information should be communicated:

      1. the lack of research on the drug
      2. questions on purity of the preparations which could lead to unusual reactions (other health food store preparations could have the same problem).
      3. interactions with other drugs
      4. possible long-term suppression of the pineal (speculative only) based on other neuroendocrine responses to, for example, thyroxin and steroid in thyroid and adrenal suppression, which implies tapering of the melatonin in the event of stopping.
      5. other unknown effects, pharmacokinetic and pharmacodynamic.
      On the other hand, melatonin remodulation appears physiological. This has not been prescribed per se but is available in certain health food stores in a 3 mg and 5 mg size. Preferable is the smallest possible dose as physiologically it is thought only 0.5 mg - 1 mg is necessary in the normal person. Preparations of animal extraction should be avoided at this point: vegetable or synthetic melatonin may prove less risky. The drug is best taken an hour before dusk and should take several weeks to work fully.

      d. Benzodiazepines: Benzodiazepines should be avoided, if possible, because of their addictive qualities and impairments at the psychomotor, cognitive, amnesic and drug interactional levels. The benzodiazepine may relieve symptoms non-specifically and incompletely but has all the cognitive, psychomotor, and dependence, addictive problems of this drug group. This may be aggravated by previous abuse history and symptomatic status.

      e. Sleep disturbance usually appears secondary in the CHIT and should be managed with no napping during the day.

      4. MANAGEMENT OF DEPRESSION AND MOOD DISORDER: Affective Disorders and Head injury
      The area of mood disorders allows possible practical and theoretical understanding of the role of the central nervous system in behavior disorders. Affective disturbances may be triggered or induced by head injury with or without patients with traumatic temporal lobe epilepsy (Neppe, Tucker 1994) and head trauma (Neppe, Tucker 1994; Tucker, Neppe 1991).

      We believe that CHIT may trigger "Depressive pseudodementia" in patients with limited cerebral reserve (MacAllister, 1983, 1992). This refers to the organic symptomatology, particularly dementing symptoms in affectively disturbed patients. Cognitive and neuropsychologic disturbances are associated with affective disturbances generally reversible with treatment. Consequently, in dealing with the demented patient, one must rule out affective disturbance in the older patient (Neppe, Tucker 1994).

      a. LITHIUM CARBONATE (ESKALITH AND OTHERS - choice is optional): occasionally lithium is useful when patients manifest cyclical phenomena of their residual focal CHIT. Medication problems with lithium are linked commonly to tremor which is a rather coarse static one which patients find impairing in functionality and embarrassing. Some patients become nauseous and/ or confused. Our preference is to lower dosage in the event of any of the above symptoms. Baseline blood tests of electrolytes and renal functions are important as is frequent monitoring for a major but neglected long-term complication nephrogenic diabetes insipidus commonly presenting as polyuria or nocturia. One way to initiate lithium is by giving 600 mg on the first day and check a level after 24 hours. This will also screen for those who become Lithium toxic rather quickly. Lithium is an extremely lethal compound and should be used under supervision of a psychiatrist. Two different blood levels can be considered: Low dose with less side-effect potential but possibly less control: aim at a blood level of 0.4-0.6 meq / L. High dose with more side-effect potential but possibly more control: aim at a blood level of 0.7-0.9 meq / L. Many colleagues use higher doses but this would not be my preference in this instance.

      b. ANTIDEPRESSANT options can be applied in the context of mobilization of significant or major depression either post-traumatically or post-concussionally in the CHIT or in alleviation of pain (not approved). Our preference is to avoid the SSRIs group as well as the tricyclics and to use nefazodone or venlafaxine as selective drugs acting reasonably physiologically at the norepinephrine and serotonin receptor levels. Bupropion may also be of value.

      b.1. NEFAZODONE (Serzone): This antidepressant of triazolopyridine structure has ideal theoretical elements both for agitated and retarded depression. The reason relates to its modulating SSRI properties which implies less side-effects such as agitation, anxiety, sexual related pathology, nausea, akathisia and suicidality. It has additionally serotonin 2 blocking effects which should enhance both antidepressant and anti-aggressive properties and further diminish SSRI side-effects. It is more sedative than the other SSRIs but far less than the triazolopyridine, Trazodone. My preference is to start with doses of 50 mg bid and increase every 3 days by 50 mg daily, always giving bid dosing until an initial dose of 200 mg bid is achieved. Doses should best be given in the morning and afternoon because of its short half life and uneven kinetics. Costs of all sizes are equal - 200 mg, 150 mg, 200 mg, 250 mg. Serzone inhibits the 3A4 part of Cytochrome P450 enzyme system in the liver. This increases levels of certain chemicals e.g. ketoconazole, alprazolam, triazolam, and probably SSRIs like fluoxetine as well as some calcium channel blockers. These substances should increase Nefazodone levels as well and a 50% dose adjustment is general rule. Particularly, do not give with Seldane (terfenadine) and Hismanal (astemizole) - if necessary change to Claritin (Loratadine) (10 mg Claritin usually equal to 10 mg Hismanal, 60 mg bid of Seldane)

      b.2. Venlafaxine (Effexor) This has the advantage of acting at both serotonin ("sledgehammer" pharmacologic) and norepinephrine ("chisel" and more physiologic) and should not produce the sexual dysfunction of the SSRIs. Its limitations relate to possible nausea, escalated blood pressure and agitation. It is logical in the retarded depressive patient.

      b.3. Bupropion (Wellbutrin): This antidepressant likely acts clinically through a somewhat irreversible norepinephric re-uptake inhibitor effect of an active metabolite hydroxy bupropion and not the dopaminergic effect previously thought. Bupropion differs from most antidepressants in its absence of effect on serotonin. Given the availability of a long-acting form, twice daily dosing is logical with a starting dose of 75 mg twice per day building if necessary to 300 mg daily. Likely choice is based on amotivation, the norepinephric effect supplementing serotonergic drugs if necessary, lack of sexual dysfunction, overweight status, and need for some activating action.

      b.4. In our opinion, the following antidepressants are not usually recommended in the CHIT patient with depression, but are commonly prescribed by some - the tricyclic antidepressant and the selective serotonin re-uptake inhibitor groups. I. Tricyclic antidepressants like nortriptyline, imipramine and desipramine. The tricyclic group has problematic side-effects namely potential epileptogenicity, memory impairments, cardiotoxicity due to arrhythmias, anticholinergic effects such as urinary retention, dry mouth, blurred vision and constipation, interaction with alcohol, and sedation. In the CHIT patient, the dysmnesic and seizure elements are particularly troublesome.

      NORTRIPTYLINE (Aventyl, Pamelor) medication. This tricyclic antidepressant is potent and can be used frequently in doses of 75 mg per day in instances requiring 150 mg of similar other tricyclic agents. Moreover the monitoring of blood levels to an antidepressant therapeutic window allows easy evaluation particularly in the complex patient on carbamazepine. Its effects are predominantly serotonergic.

      IMIPRAMINE (Tofranil) medication for biological depression is linked with seizures This is two-edged as it may exacerbate seizure phenomena. This tricyclic antidepressant is potent and can be used frequently in doses of 75 mg-150 mg per day in this case. Its effects are predominantly adrenergic.

      DESIPRAMINE (Norpramin) medication. This tricyclic antidepressant is not very potent mg for mg and is used frequently in doses of 150-225 mg per day. It is a breakdown product of imipramine. In practice, it is more activating, less sedating and causes more sweating than the more sedative tricyclics. Its effects are predominantly noradrenergic.

      II. Selective Serotonin Re-uptake Inhibitors (SSRIs) like fluoxetine, paroxetine and sertraline. This group of drugs do not have the anticholinergic nor cardiotoxic side-effects of the tricyclic antidepressants. However, they are potent serotonergic agonists with no way to diminish the effect other than breakdown of active compound. These drugs have two problematic common side-effects namely nausea and sexual dysfunction. They may paradoxically increase anxiety, irritability and agitation, accentuate nausea and disrupt sleep. There is a possible discontinuation syndrome, and clinically frequently loss of effects, or need for escalating dosage occurs over time and it is for these reasons particularly that we do not recommend the SSRIs to the CHIT patient. The serotonergic effects of all the current SSRIs appear non-specific on supposedly all serotonin receptor subtypes. As such, the risk of paradoxic reactions is theoretically higher.

      FLUOXETINE (Prozac) with its extraordinarily long half-life (>400 hours including the metabolite norfluoxetine) should be used with extreme caution. In fluoxetine particularly there is controversy surrounding precipitation of suicidality, aggression, akathisia and tardive dyskinesia.

      PAROXETINE (Paxil) does not have an active metabolite but it inhibits the hepatic P450 cytochrome enzyme system. It has a one day half life. Start with doses of 20mg per day initially and later 30 mg per day built up as necessary to 50 mg per day. SERTRALINE (Zoloft) has a minor probably non-significant active metabolite. We now know that it does effect the hepatic P450 cytochrome enzyme system so there may be drug interactions. It has a slightly longer half life than paroxetine - several days. Start with doses of 25 mg per day (half of 50 mg tablet) initially for three days and then 50 mg per day built up as necessary to 100 mg per day.

      1. PHYSIOLOGIC RESTABILIZATION by BETA-BLOCKADE if numerous somatic - bodily - symptoms exist may be considered. NADOLOL (CORGARD) medication. Beta-blockers are useful in this instance for the somatic features of anxiety and agitation. They are not specifically FDA approved for these indications. Nadolol is suggested as the only poorly lipid soluble broad-spectrum (B1 and B2) beta-adrenergic blocker which can act peripherally and because of lack of intrinsic sympathomimetic activity can be dosed according to pulse. The dose is similar to that of propranolol (Inderal). The initial starting dose usually suggested is half 20mg tablet t.i.d. i.e. 10 mg t.i.d. We suggest this be built up gradually by increasing by 10 mg every 3 days to a initial aim level of mg per day. The drug should be administered as a t.i.d. dosage and was chosen over other beta-blockers because it is not very lipid soluble (avoiding central side-effects), has both beta1 and 2 effects and has no intrinsic sympathomimetic activity so that an initial titration of dose to a pulse of 66/ minute can be aimed at. Important side-effects relevant for the patient include:
      1. Precipitation of asthma, diabetes, hypotension, cardiac failure and peripheral vascular disease leading to these conditions being contra-indicated.
      2. The awareness that too much is being taken if the pulse goes into the fifties.
      3. To contact the treating physician if signs of cardiac failure such as pedal edema develop.
      If the response to the nadolol is partial, we suggest changing to a lipid soluble betablocker - to propranolol (Inderal) and building up to a dose of about 480 mg per day or till side-effects or till pulse is = 60/minute. The change around from nadolol can be mg for mg and direct substitution from 40 mg t.i.d. nadolol to 40 mg t.i.d. of propranolol. Thereafter maintain the dose for 1 week and increase by 20mg t.i.d. more per week till 120 mg qid or pulse = 60/min pre-dosage or side-effects such as dizziness (Neppe, 1989 C).

      2. PSYCHOSTIMULANTS are occasionally worth considering in the CHIT particularly in the context of residual focal non-episodic phenomena and / or a history of paradoxic responses. These drugs should be used with caution based on potential dependence, misuse (also by others), tics and possible tachyphylactic effects. One approach is to use these drugs in both attention deficit disorder and narcoleptic syndromes as provocative pharmacologic tests: non-response without side-effects = increase the dose; worsening = take patient off; improvement = maintain.

      One preference is generally for the scheduled methylphenidate (Ritalin) which appears more effective than pemoline (Cylert) (which requires liver function tests six monthly) but requires bid or tid dosing; it should also be safer than dextro-amphetamine sulphate (abuse potential, possible potential to a "model psychosis" / paranoid syndrome). Start with 10 mg qd and build up to 10 mg tid initially over 10 days. The patient should record responsiveness.

      A second preference is for pemoline (Cylert) (which requires liver function tests six monthly) but is less highly scheduled, less likely to be abused? and cause tics? and can be given daily but it may be less effective than methylphenidate (Ritalin); it should also be safer than dextro-amphetamine sulphate (abuse potential, possible potential to a "model psychosis" / paranoid syndrome). Start with 37.5 mg qd and build up to 75 mg qd initially over 10 days. The patient should record responsiveness.

      3. ANTIPSYCHOTIC USE: Psychotic Disorders and Head injury
      There are many neurologic causes of psychosis (Table 1), particularly seizure disorders and more so complex partial seizures (or temporal lobe epilepsy). This may be a possible link of the rare onset of paranoid psychosis after brief traumatic brain injury. In 1963, Slater and Beard pointed out that all of the symptoms that have been observed in schizophrenic patients can occur in patients with seizure disorders. Recent efforts using standardized diagnostic rating scales have shown that the positive symptoms of the psychotic state of patients with temporal lobe seizure disorders is almost identical to schizophrenics (Trimble, 1982; Toone, 1981). Seizure disorders present with a high incidence of behavioral disturbance, which may initially be interpreted as psychiatric in origin (Neppe, Tucker, 1994). The range of behavioral symptoms is listed in Table II and most patients have only one or two of these symptoms that remain consistent over the course of the illness. (Neppe, 1989 D)

      NEUROLEPTICS (antipsychotics; also called major tranquilizers) should be avoided in the head injured as there is a higher risk of tardive dyskinesia (Neppe, Holden, 1989; Neppe 1989 D). Exceptions relate to the very occasional presence of or exacerbation of psychosis. PERPHENAZINE (TRILAFON) medication has become our preferential drug in post-traumatic psychosis as part of the residual focal elements of the CHIT. Perphenazine is approved for use in psychotic conditions. Amongst the important side-effects discussed is the long term risk of tardive dyskinesia and related syndromes and its relevance to diagnosis, dosage, duration of treatment, smoking epidemiology and the limited amounts of treatment. Anticholinergic medication is sometimes prescribed to alleviate the extra-pyramidal side-effects of neuroleptic drugs. The patient should not routinely receive anticholinergic agent with the perphenazine as this complicates pharmacokinetics, may accentuate psychosis, is usually unnecessary and disputably increases the risk of tardive dyskinesia. Additionally, anticholinergics mask neuroleptic dosage somewhat. Also, additional potential side-effects of dry mouth, dilated pupils with blurring of vision, constipation, confusion, memory impairment and delirium may occur (Neppe, Ward, 1989). When there is a previous history of response to anticholinergics but with side-effects of sedation, an anticholinergic which is relatively non-sedative, has low abuse potential, and which moreover has some muscle relaxant effect, orphenadrine (Norflex) is recommended. Usual doses are 50 mg TID. If not tolerated, lower doses can be tried. A maximum of 100 mg tid should be used. The most commonly used anti-Parkinsonian anticholinergic in the USA appears to be benztropine (Cogentin).


      a. ANTI-OXIDANTS A recent area of some interest, theoretical speculation and difficulty appreciating cause-effect relationships and consequent therapeutic efficacy is the use of anti-oxidant medications in instances of neuronal or neurologic diseases including pervasive developmental disorder, Landau-Kleffner syndrome, atypical epilepsies, multiple sclerosis, and mental retardation. These organic brain conditions may or may not prove to have end point biochemical similarities with CHIT. Anti-oxidants should be considered if the profile includes abnormal glutathione enzymes like Glutathione peroxidase and transferase, and various trace elements like Selenium plus a Lipid peroxide index. These cannot be measured but speculatively may be abnormal in a CHIT with residual or post-concussional elements. The following guidelines are thought appropriate at this time:

      RX Medication  size  Dosing  comments
      Vitamin C  1500 mg long acting  1500 mg BID Or Daily 
      Vitamin E as D tocopherol  400 iu  400 iu BID  use d isomer of tocopherol if possible 
      Selenized yeast  100 ug Selenium  100 ug BID  This is thought to be toxic beyond doses of 800 ug per day 

      Target symptoms to monitor at are energy, lethargy, concentration, daydreams, communication

      b. MINERAL, VITAMIN, OMEGA SUPPLEMENTATION Chromium picolinate 200 ug to 400 ug daily, Magnesium ion e.g. as chloride 400 mg per day (with some calcium if necessary to avoid diarrhea), and Zinc 15 mg daily and the Omega fatty acids are interesting mineral and vitamin or food supplements in this kind of patient. There is limited uncontrolled or anecdotal or lay literature suggesting this combination may assist potential towards hypoglycemia and may allow weight control (particularly chromium based on its controversial effect in relation to glucose cell utilization and possibly zinc), lower risk of heart attack (magnesium particularly) and diminished seizure risk (magnesium and secondarily chromium). Obviously, such supplementation is unnecessary in some but as it is not easy to distinguish in any particular case, and the patient may wish to explore these possibilities ensuring that the best quality brands are bought and knowing that besides risks linked with the vehicles containing these medications (as with any vitamin or mineral or sometimes generic type medication) there may be unknown interactions occurring.


      We are doing a full circle. Cesare Lombroso, last century wrote about the constitutional psychopath (Lombroso, 1912). Sociologists and behaviorist psychologists claimed that there were no such constitutional givens and that all behavior was socially determined totally ignoring the organism. We have now returned to the stage where constitutional and biologic components have again become important and well demonstrated in our conceptualization of transient traumatic head injury.

      Lewis D, Balla D (1976) Delinquency and Psychopathology. New York, Grune & Stratton

      Lombroso Cesare (1912) Crime, Its Causes and Remedies. Tranol, Horton HP. Boston, Little Brown & Co.

      MacAllister T (1983) Pseudodementia. Am J Psychiatry, 140:528,

      McAllister, T.W. (1992). Neuropsychiatric sequelae of head injuries. Psychiatric Clinics of North America, 15 (2), 395-415.

      Neppe VM.( 1982A) The new classification of epilepsy--an improvement? S Afr Med J.; 61 (7): 219-20.

      Neppe VM. (1982 B). Olfactory hallucinations in the subjective paranormal experient. Proceedings , Centenary SPR/Jubilee PA Convention, Cambridge, England.; 2 1-17.

      Neppe VM (1983 A)The Psychology of Deja Vu: Have I been Here Before? Johannesburg: Witwatersrand University Press. 1-277 & I-XLV

      Neppe VM: (1983 B). The olfactory hallucination in the psychic, In: Roll WG, Beloff, J, White, RA, eds. Research in Parapsychology 1982. Metuchen, NJ.: Scarecrow Press;: 234-237

      Neppe V M (1983 C) Temporal lobe symptomatology in subjective paranormal experients. J Amer Soc Psychic Research. 77:1, 1-29

      Neppe V M (1983 D) Anomalies of smell in subjective paranormal experients. Psychoenergetics - J Psychophysical Systems. 5:1, 11-27

      Neppe VM: (1984A). The management of psychoses associated with complex partial seizures, In: Carlile JB, eds. Update on Psychiatric Management. Durban: MASA;: 122-127.

      Neppe VM: (1984B). Phenomenology and the temporal lobe, In: Roll WG, Beloff, J, White, RA, eds. Research in Parapsychology 1983. Metuchen, NJ.: Scarecrow Press

      Neppe VM (1985A) Kindling and neuropsychological change: A model of dopaminergic involvement., In: eds. Neuropsychology 2 - Proceedings, Second South African Congress of Brain and Behaviour. Pretoria, RSA: SA Brain and Behaviour Society (SABBS); 57-62.

      Neppe VM (1985B) The kindling phenomenon implications for animal and human behaviour. In: eds. Neuropsychology 2 - Proceedings, Second South African Congress of Brain and Behaviour. Pretoria, RSA: SA Brain and Behaviour Society (SABBS); 47-51.

      Neppe VM (1985C) Non-responsive psychosis: Neuropsychological rehabilitation by antikindling agents., In: eds. Neuropsychology 2 - Proceedings, Second South African Congress of Brain and Behaviour. Pretoria, RSA: SA Brain and Behaviour Society (SABBS);: 52-56.

      Neppe VM. (1988) Carbamazepine Use in Neuropsychiatry. J Clin Psychiatry Supplement 4. ; 1-1-64.

      Neppe VM (1989 A) The clinical neuropharmacology of buspirone, In: Neppe VM, eds. Innovative Psychopharmacotherapy. New York: Raven Press;: 35-57 , Ch 2.

      Neppe VM (1989 C) Carbamazepine, limbic kindling and non-responsive psychosis, In: Neppe VM, eds. Innovative Psychopharmacotherapy. New York: Raven Press; 1989B: 123-151 , Ch 5.

      Neppe VM: Beta-adrenergic blocking agents: perspectives in psychiatry, In: Neppe VM, eds. Innovative Psychopharmacotherapy. New York: Raven Press;: Ch 1, 1-34.

      Neppe VM (1989 D) Psychopharmacological strategies in non-responsive psychotics, In: Neppe VM, eds. Innovative Psychopharmacotherapy. New York: Raven Press; : Ch 4, 94-122.

      Neppe VM (1990 A) Buspirone: an anxioselective neuromodulator, In: Neppe VM, eds. Innovative Psychopharmacotherapy. New York: Raven Press;: 35-57 , Ch 2.

      Neppe VM (1990 B) Carbamazepine in the non affective psychotic and non psychotic dyscontrol., In: Emrich H, Schiwy, W, Silverstone, T, eds. Carbamazepine and ox-carbazepine in psychiatry: International Clinical Psychopharmacology. London: Clinical Neuroscience Publishers;: 43 -54.

      Neppe VM, Bowman, B, Sawchuk, KSLJ. (1991) Carbamazepine for atypical psychosis with episodic hostility. J Nerv Ment Dis.; 179 (7): 339-340.

      Neppe VM (1993 A) Serotonin 1A neuromodulators: clinical implications for the elderly, In: Bergener M, Belmaker, RH, Tropper, MS, eds. Psychopharmacology for the Elderly: Research and Clinical Implications. New York: Springer Publ Co;: 222-238.

      Neppe VM, Goodwin G, (1998, in press) The Neuropsychiatric Evaluation of the Closed Head Injury of Transient Type (CHIT)

      Neppe VM , Holden, T (1989) Innovations in schizophrenia management, In: Neppe VM, eds. Innovative Psychopharmacotherapy. New York: Raven Press;: Ch 3, 58-93.

      Neppe VM, Tucker, GJ. (1988 A). Modern perspectives on epilepsy in relation to psychiatry: classification and evaluation. Hosp Community Psychiatry. 39 (3): 263-71

      Neppe VM, Tucker, GJ. (1988 B). Modern perspectives on epilepsy in relation to psychiatry: behavioral disturbances of epilepsy. Hosp Community Psychiatry.; 39 (4): 389-396.

      Neppe VM, Tucker, GJ: (1989). Atypical, unusual and cultural psychoses, In: Kaplan HI, Sadock, BJ, eds. Comprehensive Textbook of Psychiatry, Fifth Edition. Baltimore: Williams and Wilkins;: 842-852, Ch 10.

      Neppe VM, Tucker, GJ. (1992).: Neuropsychiatric aspects of seizure disorders, In: Yudofsky SC, Hales, RE, eds. Textbook of Neuropsychiatry. Washington, D.C.: American Psychiatric Press; : 397-426.

      Neppe VM, Tucker, GJ. (1994). Neuropsychiatric aspects of epilepsy and atypical spells, In: Yudofsky SC, Hales, RE, eds. Synopsis of Textbook of Neuropsychiatry. Washington, D.C.: American Psychiatric Press;: 397-426.

      Neppe VM, Tucker, GJ , Wilensky, AJ. (1988 C) Fundamentals of carbamazepine use in neuropsychiatry. J Clin Psychiatry.; 49 (4 suppl): 4-6.

      Neppe VM, Ward, NG (1989) The management of neuroleptic-induced acute extrapyramidal syndromes., In: Neppe VM, eds. Innovative Psychopharmacotherapy. New York: Raven Press Ch 6, 152-176.

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      Slater E, Beard A, Glithero (1963) The schizophrenia-like psychosis of epilepsy. Br J Psychiatry, 109:95-105

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      Toone B (1981) The psychosis of epilepsy. In Psychiatry, Reynolds E, Trimble M (eds), Epilepsy and Psychiatry. Edinburgh, Churchill Livingstone

      Trimble M, Perez M (1982) The phenomenology of the chronic psychosis of epilepsy. Adv. Biol Psychiatry, 8:98-105

      Tucker GJ, Neppe, VM. (1988). Neurology and psychiatry. Gen Hosp Psychiatry.; 10 (1): 24-33.

      Tucker GJ, Neppe, VM: (1991) Neurologic and neuropsychiatric assessment of brain injury, In: Doerr HO, Carlin, AS, eds. Forensic Neuropsychology : Legal and scientific basis. New York: Guilford;: 70-85.

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      TABLE 1

      International League Against Epilepsy Revised Classification of Epileptic Seizures (1981)
      1. Partial (focal, local) seizures:
        1. Simple - motor, somatosensory, autonomic, psychic
        2. Complex
          1. Impaired consciousness at outset
          2. Simple partial followed by impaired consciousness
        3. Partial seizures evolving to generalized tonic-clonic (GTC)
          1. Simple to GTC
          2. Complex to GTC
      2. Generalized seizures (convulsive or non-convulsive)
          1. Absence seizures
          2. Atypical absences
        1. Myoclonic
        2. Clonic
        3. Tonic
        4. Tonic-clonic
        5. Atonic
        6. Combinations
      3. Unclassified epileptic seizures


      Controversial PTLSs (CPTLSs)
      1. severe hypergraphia
      2. severe hyperreligiosity
      3. polymodal hallucinatory experience Paroxysmal (Recurrent) Episodes of:
      4. profound mood changes within hours
      5. frequent subjective paranormal experiences e.g. telepathy, mediumistic trance, writing automatisms, visualization of presences or of lights/colors round people, dream ESP, out-of body experiences, alleged healing abilities
      6. intense libidinal change
      7. Uncontrolled, lowly precipitated, directed, non-amnesic aggressive episodes;
      8. recurrent nightmares of stereotyped kind
      9. episodes of blurred vision or diplopia
      Not Necessarily Disintegrative PTLSs (NPTLSs)

      Symptoms Not Necessarily Requiring Treatment Paroxysmal (Recurrent) Episodes of:

      1. Complex visual hallucinations linked to other qualities of perception such as voices, emotions, or time



        Any form of:

      1. Auditory perceptual abnormality;
      2. Olfactory hallucinations;
      3. Gustatory hallucinations;
      4. Rotation or disequilibrium feelings linked to other perceptual qualities;
      5. Unexplained "sinking," "rising," or "gripping" epigastric sensations;
      6. Flashbacks;
      7. Illusions of distance, size (micropsia, macroscopy), (micropsia), loudness, tempo, strangeness, unreality, fear, sorrow;
      8. Hallucinations of indescribable modality.
      9. Temporal lobe epileptic deja vu (has associated ictal or postictal features {headache, sleepiness ,confusion} linked to the experience in clear or altered consciousness )
      10. Any CPTLSs which appear to improve after administration of an anticonvulsant agent such as carbamazepine.
      Disintegrative PTLSs (DPTLSs)

      Symptoms Requiring Treatment: Paroxysmal (Recurrent) Episodes of:

      1. Epileptic amnesia;
      2. Lapses in consciousness;
      3. Conscious "confusion" ("clear" consciousness but abnormal orientation, attention and behavior);
      4. Epileptic automatisms;
      5. Masticatory-salivatory episodes;
      6. Speech automatisms;
      7. "Fear which comes of itself" linked to other disorders (hallucinatory or unusual autonomic) ;
      8. Uncontrolled, unprecipitated, undirected, amnesic aggressive episodes;
      9. Superior quadrantic homonymous hemianopia;
      10. Receptive (Wernicke's) aphasia.
      11. Any CPTLSs or NPTLSs with ictal EEG correlates.
      Seizure related features (SZs)

      Any typical absence, tonic or clonic or tonic-clonic or bilateral myoclonic seizures in the absence of metabolic, intoxication or withdrawal related phenomena.




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