FOLLOW-UP
Diminished AAI is a dynamic condition, and evolves with time from the intracranial event.  The patient should be assessed every few months with a trial taper to determine if psychostimulants are still required, as anatomically intact but physiologically "stunned" neurons may recover.  Clinical decompensation must also be investigated, as post-traumatic hydrocephalus, aneuryms, meningitis, abscess, and other conditions may occur and require definitive medical or surgical management. 

Rechallenge of psychostimulants previously documented as inefficacious should also be considered, as edema resolution and neurologic anatomic regrowth or unmasking of preserved systems may imbue new responsiveness to psychostimulants previously documented as inefficacious in a particular individual at a particular stage in healing.  Selegiline given to a patient receiving concomitant bromocriptine and Sinemet resulted within 7 months in mania,(146) and illustrates the importance of continued clinical monitoring of patients receiving dopaminergics.

Development of irritability may occur with long term use,(64) and dose reduction may be required to maximize quality of life and social performance.  A retrial at a higher dose after the irritability has subsided may afford resumption of previously maximized AAI without recurrence of irritability.(64) 

Though the long term efficacy and safety of psychostimulants has been well established,(2) a small subpopulation of patients may develop tolerance(109) and require higher doses as the brain heals and better processes data.  Efficacy of amantadine may decrease after months of continued use.(4)  "Tolerance" to the beneficial effects of psychostimulants may occur, as described after a year of  protriptyline(114) or one to two months of methylphenidate.(114)  Just as some patients with Parkinson's disease exhibit a decline in clinical efficacy over the first few months,(64) so too may psychostimulant efficacy fade in an undefined subpopulation of patients with the passage of time.(2)  Follow-up is invaluable to evaluate patients for alternative drug options.


FUTURE DIRECTIONS
Further research is required to define if a critical period exists during after which pharmacological intervention is no longer efficacious to enhance AAI.   Alternatively, a therapeutic window of maximal efficacy may be identified.  Serial PET scans may correlate cerebral hemodynamic and metabolic responsivity of various lesions and clinical expressions to individual drug trials.  The phenomenon of tolerance to TCA's(7) must be investigated.  Presynaptic neuron down-regulation in response to Sinemet with consequent inefficacy has been suggested(98) and must be further explored. 

A therapeutic maximum dose may exist in which excessive dosing may precipitate post-synaptic receptor downregulation or diminished presynaptic neurotransmitter synthesis.  Identification of such a dose or excessive daily frequency or protracted duration of delivery may enormously benefit patients who might otherwise be designated nonresponders or rapid acclimators.  Potential synergism between agents of different classes and those of the same class, such as amantadine and bromocriptine must also be investigated. 

If dopaminergic psychostimulant efficacy is felt to be mediated by DA-3 or other non-DA-2 or DA-4 activity, then future molecular engineering may synthesize receptor specific agents which can be used safely in patients with premorbid histories of psychosis and need for psychosis suppression via DA-2 or DA-4 blockade.  The value of DA-1 agonism remains to be defined.  Effects of different agents on various subcomponents of attention must continue to be investigated in randomized prospective studies.  It will also be of valuable clinical interest to identify if an optimal duration of initial psychostimulant treatment influences whether the system can be reset to eventually achieve functional autonomy without exogenous intervention.

A triphasic response to bromocriptine has been identified with maximal dopamine agonism only at the mid-range doses.(33)  The etiology of this remains to be identified as receptor saturation, downregulation, metabolism kinetics, or other etiology.  Similar occurrences for other psychostimulants remains to be investigated. 

Earlier delivery of the medication may promote recovery and restoration of neurologic integrity with consequent improved function rather than enhance function of irreversably damaged neurones.  If this is true, then the former intervention may afford greater eventual function and potentially less dependency on continued drug delivery for maintenance of function.(123) 


MEDICAL MANAGEMENT IN THE INTERIM

A great number of organ systems can decompensate in the comatose, vegetative, and locked in patient if not properly treated.

MEDICAL MANAGEMENT IN THE INTERIM – VASCULAR

During the inpatient stay and for 6 weeks – 6 months, heparin should be given daily to prevent deep venous thrombosis and potentially fatal pulmonary embolus.  Aspirin does not prevent thrombosis or embolus.

MEDICAL MANAGEMENT IN THE INTERIM – GASTRO-INTESTINAL

All patients who suffer an acute neurologic insult are at heightened risks for peptic ulceration and potentially fatal bleeding.  Proton pump inhibitors such as Aciphex should be given to greatly diminish risks.  This author prefers Aciphex over Nexium, Prevacid, Protonix, and Prilosec as Aciphex reportedly is the only proton pump inhibitor which blocks all four acid channels in the stomach.

Patients with low levels of AAI still require general medical care in terms of cancer screening with colonoscopy, pap smears, testicular exams, prostatic specific antigen (PSA), breast exams, and mammograms.

Patients whose TBI was felt to be related to alcohol and other substance abuse should be tested with a hepatitis panel as diagnosis of this condition will dictate safety of psychostimulant medication trials as well as permit treatment of the hepatitis itself.  HIV testing should also be entertained.

MEDICAL MANAGEMENT IN THE INTERIM – GENITO-URINARY
Bladder emptying should be performed with suprapubic tapping and scheduled straight catheterization.  Males should use condom catheters if low post-void residuals can be confirmed.  Indwelling urethral catheters enormously increase the risks for sepsis and death.  Methenamine decreases the risks for urinary tract infections unless the patient is inappropriately managed with an indwelling catheter.  Cranberry juice fed via the G-tube may decrease the likelihood that E. coli bacteria will adhere to the bladder wall to cause infection.

Patients with low levels of AAI still require general medical care in terms of cancer screening with pap smears, testicular exams, prostatic specific antigen testing (PSA), breast exams, mammograms, and colonoscopy.

Urodynamic testing may be required to identify external sphincter dyssynergia.

MEDICAL MANAGEMENT IN THE INTERIM - PULMONARY
Chest percussion, good hydration, and frequent suctioning decreases the risks for atalectasis and pneumonia.  Pneumococcus vaccination should be given in the acute care hospital and repeated every five years to reduce the risks for pneumonia.  Influenza vaccination should be given annually, early in the season.

MEDICAL MANAGEMENT IN THE INTERIM – CARDIAC
Premorbid medical conditions are often neglected in the TBI, stroke, and otherwise neurologically devastated.  Aspirin, Plavix, and Aggrenox should be delivered to prevent potentially fatal myocardial ischemia or recurrent stroke. 

MEDICAL MANAGEMENT IN THE INTERIM – HEMATOPOETIC
Folic acid should be given to 100% of patients consuming chronic Dilantin therapy to prevent macrocytic anemia.

MEDICAL MANAGEMENT IN THE INTERIM - SKIN

Patients should be repositioned to rest on their sides as well as back every few hours.  Skin overlying superficial bone such as the greater trochanters, heels, elbows, and ischial tuberosities are prone to decubitii which may erode into bone and necessitate amputation or death from sepsis.  Elbow pads should be worn.  Multipodus L’Nard boots should be worn to elevate the heel from the bed such that it is suspended in air and unable to rapidly develop a pressure ulcer.  Bunny foam boots are fully inadequate. 

MEDICAL MANAGEMENT IN THE INTERIM – MUSCLE, TENDON CONTRACTURES
Family members should be taught stretching exercises to prevent knee flexion, elbow flexion, shoulder adduction, wrist flexion, and finger flexion contractures.  Botulinum and phenol spastic hypertonus reducing injections may be required.  Resting wrist splints, knee extension, and other splinting interventions are enormously helpful.

EVERY PATIENT DESERVES A CHANCE!!!