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Ali, S. O., K. D. Denicoff, et al. (2000). "A preliminary study of the relation of
neuropsychological performance to neuroanatomic structures in bipolar disorder."
Neuropsychiatry, Neuropsychology, & Behavioral Neurology 13(1): 20-8.
OBJECTIVE: To investigate the relation between neuropsychological dysfunction
and volumetric measures of neuroanatomic structures in patients with bipolar
disorder. BACKGROUND: Previous research suggests that neuropsychological
deficits are associated with neuroanatomic changes in patients with bipolar
disorder. METHOD: Twenty-six outpatients who met Diagnostic and Statistical
Manual, Third Edition-Revised criteria for bipolar disorder were administered a
battery of neuropsychological tests that assessed memory, abstracting ability,
psychomotor performance, sustained attention, and intelligence. Patients also
received a magnetic resonance imaging scan, from which volumes of the
temporal lobes, hippocampus, third ventricle, and areas of the lateral ventricles
were calculated. Using multiple regression analyses, neuroanatomic structures
were compared with neuropsychological test variables. RESULTS: Data suggest
that a larger right hippocampal volume is associated with poorer
neuropsychological functioning. CONCLUSIONS: Further studies are needed to
both replicate and examine the relation between potential mechanisms of
neuroanatomic alterations and neuropsychological dysfunction in patients with
bipolar disorder.
Bostwick, J. M. and K. L. Philbrick (2002). "The use of electroencephalography in
psychiatry of the medically ill." Psychiatric Clinics of North America 25(1): 17-25.
The psychiatrist considering recommending an EEG should look for acute
changes in the history or examination suggestive of an organic cause. If he or
she judges that the EEG will help to clarify or confirm the diagnostic impression
already formulated, it is worth considering whether adding provocative
maneuvers could increase the yield. The authors cannot overemphasize the
importance of using the EEG in correlation to further inform old-fashioned clinical
detective work already in process, particularly when the EEG could rule out a
potential organic contributor to a psychiatric phenotype. For routine screening
without an elevated index of suspicion or for thoughtless "fishing expeditions,"
EEG results will surely disappoint.
Bracha, H. S., E. Garcia-Rill, et al. (2005). "Postmortem locus coeruleus neuron count in
three American veterans with probable or possible war-related PTSD." Journal of
Neuropsychiatry & Clinical Neurosciences 17(4): 503-509.
The authors investigated whether war-related posttraumatic stress disorder (WRPTSD) is associated with a postmortem change in neuronal counts in the locus
coeruleus (LC) since enhanced central nervous system (CNS) noradrenergic
postsynaptic responsiveness has been previously shown to contribute to PTSD
pathophysiology. Using postmortem neuromorphometry, the number of neurons
in the right LC in seven deceased elderly male veterans was counted. Three
veterans were classified as cases of probable or possible WR-PTSD. All three
veterans with probable or possible WR-PTSD were found to have substantially
lower LC neuronal counts compared to four comparison subjects (three
nonpsychiatric veterans and one veteran with alcohol dependence and delirium
tremens). To the authors' knowledge, this case series is the first report of LC
neuronal counts in patients with PTSD or any other DSM-IV-TR anxiety disorder.
Previous postmortem brain tissue studies of Alzheimer's Disease (AD)
demonstrated an upregulation of NE biosynthetic capacity in surviving LC
neurons. The finding reported is consistent with the similar upregulation of NE
biosynthetic capacity of surviving LC neurons in veterans who developed WRPTSD. Especially if replicated, this finding in WR-PTSD may provide further
explanation of the dramatic effectiveness of propranolol and prazosin for the
secondary prevention and treatment of PTSD, respectively. The LC neurons
examined in this study are probably the origin of the first or second "leg" of what
might be termed the PTSD candidate circuit. Larger neuromorphometric studies
of the LC in veterans with WR-PTSD and in other development-stress-induced
and fear-circuitry disorders are warranted, especially using VA registries.
[References: 38]
Caeiro, L., J. M. Ferro, et al. (2004). "Delirium in the first days of acute stroke." Journal
of Neurology 251(2): 171-8.
BACKGROUND AND PURPOSE: Delirium is an acute, transient disorder of
cognition and consciousness with fluctuating intensity. The aim of this study was
to investigate the presence and the risk factors for delirium in the first days after
stroke onset. PATIENTS AND METHODS: We assessed delirium prospectively
in a sample of 218 consecutive patients (mean age 57 years) with an acute (</=
4 days) stroke (28 subarachnoid haemorrhages, 48 intracerebral haemorrhages,
142 cerebral infarcts) and in a control group of 50 patients with acute coronary
syndromes with the Delirium Rating Scale (DRS) (cut-off score >/= 10).
RESULTS: 29 (13%) acute stroke patients (mean DRS score = 13.2, SD = 2.3)
and only one (2 %) acute coronary patient had delirium (chi(2) = 5.2, p = 0.02). In
nine patients delirium was secondary to stroke without any additional cause, in
10 patients there were also medical complications and in the remaining 10 there
were multiple potential causes for delirium. Delirium was more frequent after
hemispherical than after brainstem/cerebellum strokes (p = 0.02). No other
statistically significant associations with stroke locations were found. Medical
complications (OR = 4.3; 95% CI = 1.8 to 10.2), neglect (OR = 3.5; 95% CI = 1.3
to 9.2), intracerebral haemorrhage (OR = 3.1; 95% CI = 1.3 to 7.5) and age >/=
65 (OR = 2.4; 95% CI = 1.0 to 5.8) were independent factors to the development
of delirium in stroke patients. CONCLUSION: Delirium was more frequent in
stroke than in coronary acute patients. Among stroke patients, delirium was most
frequent in older patients, in those with neglect, with medical complications and
with intracerebral haemorrhages. These findings indicated that delirium in acute
stroke patients 1) is not a non-specific consequence of acute disease and
hospitalisation and 2) is secondary to hemisphere brain damage and to metabolic
disturbances due to medical complications.
Cavaliere, F., F. D'Ambrosio, et al. (2005). "Postoperative delirium." Current Drug
Targets 6(7): 807-14.
Delirium is a global impairment of upper brain functions caused by an organic
substrate. It is frequently observed in the postoperative period, particularly in
elderly people. Vascular and orthopedic surgery and long-duration surgery are
associated with a higher incidence of postoperative delirium. When it occurs,
postoperative delirium makes patient management much more difficult, increases
costs, and, above all, causes severe discomfort to the patient. Delirium is also
associated with higher postoperative mortality and morbidity, and with delayed
functional recovery, but it is still unclear whether worse prognosis is directly
caused by delirium or results from the neurological damage of which delirium is
simply a symptom. Drug therapy should be part of a complex approach to
prevent and treat this complication. Neuroleptics like haloperidol and droperidol,
and benzodiazepines are usually employed in order to control symptoms like
agitation, restlessness, and altered perceptions. Atypical neuroleptics, like
risperidone, have not yet been studied in postoperative delirium, although some
case reports in which they were successfully used have been published.
Physiostigmine is effective in delirium caused by anticholinergic syndrome;
vitamins may be useful in alcoholics; melatonin use has been suggested in order
to prevent and treat delirium by normalizing sleep-wake cycle alterations.
Environmental interventions are often costless and may be very useful to prevent
and treat postoperative delirium in patients at risk. [References: 80]
Chan, D. and N. J. Brennan "Delirium: making the diagnosis, improving the prognosis."
Geriatrics 54(3): 28-30.
Delirium is a common development in at-risk older patients hospitalized for acute
illness or postoperative care. Although delirium's risk factors are well
documented, less is known about its pathophysiology and long-term prognosis or
about the relationship between delirium, dementia, and depression. Evaluation
and management of delirium is a medical emergency. Diagnostic tools include
the Confusion Assessment Method rating scale, patient history from capable
informants, and physical/mental examinations. Management consists of
prevention, treatment of underlying causes or associated factors, supportive
care, and pharmacologic intervention (as indicated). Studies that have looked at
the reversibility of delirium suggest that patients often are slow to recover their
previous level of function. [References: 21]
Cole, M., J. McCusker, et al. (2003). "The prognostic significance of subsyndromal
delirium in elderly medical inpatients." Journal of the American Geriatrics Society 51(6):
754-60.
OBJECTIVES: To determine the prognostic significance of subsyndromal
delirium (SSD) presentations. DESIGN: Cohort study. SETTING: Universityaffiliated primary acute care hospital. PARTICIPANTS: One hundred sixty-four
elderly medical inpatients who did not meet Diagnostic and Statistical Manual of
Mental Disorders, Third Edition, Revised (DSM-III-R) criteria for delirium during
the first week after admission were classified into three mutually exclusive
groups. The first group, prevalent SSD, included those who had two or more of
four core symptoms of delirium (clouding of consciousness, inattention,
disorientation, perceptual disturbances) at admission. The second group, incident
SSD, included those who did not meet criteria for prevalent SSD but displayed
one or more new core symptoms during the week after admission. The third
group had no prevalent or incident SSD. The three groups were followed up at 2,
6, and 12 months. MEASUREMENTS: Outcomes (length of stay, symptoms of
delirium (Delirium index), cognitive (Mini-Mental State Examination) and
functional status (instrumental activities of daily living), and mortality) were
compared using univariate techniques and multivariate regression models that
adjusted for age, sex, marital status, living arrangements before admission,
comorbidity, clinical and physiological severity of illness, and dementia status
and severity. RESULTS: Patients with prevalent SSD had longer acute care
hospital stay, increased postdischarge mortality, more symptoms of delirium, and
a lower cognitive and functional level at follow-up than patients with no SSD.
Most of the findings for incident SSD were similar but not statistically significant.
Patients with prevalent or incident SSD had risk factors for DSM-defined delirium.
CONCLUSION: SSD in elderly medical inpatients appears to be a clinically
important syndrome that falls on a continuum between no symptoms and DSMdefined delirium.
Edlund, A., M. Lundstrom, et al. (1999). "Clinical profile of delirium in patients treated for
femoral neck fractures." Dementia & Geriatric Cognitive Disorders 10(5): 325-9.
The incidence of delirium, its predisposing factors, clinical profile, associated
symptoms and consequences were investigated in 54 consecutive patients, 19
men and 35 women, mean age 77.1 years, admitted to an 'ortho-geriatric unit'
with femoral neck fractures. The incidence of postoperative delirium was 15/54
(27.8%) and a logistic regression model found that dementia and a prolonged
waiting time for the operation increased the risk of postoperative delirium.
Delirium during the night was most common but in 5 patients the delirium was
worst in the morning. Patients with delirium suffered more anxiety, depressed
mood, emotionalism, delusions and hallucinations. A larger proportion of patients
with delirium could not return to their previous dwelling, and a larger proportion of
delirious patients were either dead, wheelchair-bound or bedridden at the 6month follow-up (p < 0.005). The conclusion is that delirium is common and has a
serious impact on the outcome after hip fracture surgery.
Eikelenboom, P. and W. J. Hoogendijk (1999). "Do delirium and Alzheimer's dementia
share specific pathogenetic mechanisms?" Dementia & Geriatric Cognitive Disorders
10(5): 319-24.
Dementia is the most common risk factor for delirium in the elderly. Here we will
review the evidence that proposed pathogenetic mechanisms for delirium (such
as reduced cerebral metabolism, imbalance of the noradrenergic/cholinergic
neurotransmission, inflammation, disturbances in neuronal systems which
regulate stress and the sleep/wake cycle) are also a part of the pathophysiology
of Alzheimer's disease. In particular, the role of inflammatory mechanisms in both
disorders will be discussed. [References: 44]
Ely, E. W., A. Shintani, et al. (2004). "Delirium as a predictor of mortality in mechanically
ventilated patients in the intensive care unit.[see comment]." JAMA 291(14): 1753-62.
CONTEXT: In the intensive care unit (ICU), delirium is a common yet
underdiagnosed form of organ dysfunction, and its contribution to patient
outcomes is unclear. OBJECTIVE: To determine if delirium is an independent
predictor of clinical outcomes, including 6-month mortality and length of stay
among ICU patients receiving mechanical ventilation. DESIGN, SETTING, AND
PARTICIPANTS: Prospective cohort study enrolling 275 consecutive
mechanically ventilated patients admitted to adult medical and coronary ICUs of
a US university-based medical center between February 2000 and May 2001.
Patients were followed up for development of delirium over 2158 ICU days using
the Confusion Assessment Method for the ICU and the Richmond AgitationSedation Scale. MAIN OUTCOME MEASURES: Primary outcomes included 6month mortality, overall hospital length of stay, and length of stay in the post-ICU
period. Secondary outcomes were ventilator-free days and cognitive impairment
at hospital discharge. RESULTS: Of 275 patients, 51 (18.5%) had persistent
coma and died in the hospital. Among the remaining 224 patients, 183 (81.7%)
developed delirium at some point during the ICU stay. Baseline demographics
including age, comorbidity scores, dementia scores, activities of daily living,
severity of illness, and admission diagnoses were similar between those with and
without delirium (P>.05 for all). Patients who developed delirium had higher 6month mortality rates (34% vs 15%, P =.03) and spent 10 days longer in the
hospital than those who never developed delirium (P<.001). After adjusting for
covariates (including age, severity of illness, comorbid conditions, coma, and use
of sedatives or analgesic medications), delirium was independently associated
with higher 6-month mortality (adjusted hazard ratio [HR], 3.2; 95% confidence
interval [CI], 1.4-7.7; P =.008), and longer hospital stay (adjusted HR, 2.0; 95%
CI, 1.4-3.0; P<.001). Delirium in the ICU was also independently associated with
a longer post-ICU stay (adjusted HR, 1.6; 95% CI, 1.2-2.3; P =.009), fewer
median days alive and without mechanical ventilation (19 [interquartile range, 423] vs 24 [19-26]; adjusted P =.03), and a higher incidence of cognitive
impairment at hospital discharge (adjusted HR, 9.1; 95% CI, 2.3-35.3; P =.002).
CONCLUSION: Delirium was an independent predictor of higher 6-month
mortality and longer hospital stay even after adjusting for relevant covariates
including coma, sedatives, and analgesics in patients receiving mechanical
ventilation.
Fann, J. R., C. M. Alfano, et al. (2005). "Clinical presentation of delirium in patients
undergoing hematopoietic stem cell transplantation." Cancer 103(4): 810-20.
BACKGROUND: Delirium is common in patients undergoing hematopoietic stem
cell transplantation (HSCT) and is associated with considerable morbidity and
excess mortality in diverse patient samples. Although delirium can be treated
successfully, it is largely undiagnosed. Understanding the clinical presentation of
delirium may help improve the recognition of delirium in these patients. In the
current study, the authors investigated the clinical presentation of delirium in
HSCT patients, including the time course of these symptoms and comorbid
affective distress, fatigue, and pain. METHODS: Ninety patients ages 22-62
years were recruited prior to undergoing their first allogeneic or autologous
HSCT. Delirium, distress, and pain symptom assessments were conducted
prospectively 3 times per week from pretransplantation through Day 30
posttransplantation. RESULTS: Delirium episodes occurred in 50% of patients
and lasted approximately 10 days, with peak severity at the end of the second
week posttransplantation. Factor analysis revealed three groups of delirium
symptoms representing psychosis-behavior, cognition, and mood-consciousness.
Delirium episodes were characterized by rapid onset of psychomotor and sleepwake cycle disturbance that persisted and cognitive symptoms that continued to
worsen throughout much of the episode. Rises in psychosis-behavior and
cognitive symptoms predated the start of delirium episodes by approximately 4
days. Affective distress and fatigue were common and appeared to be
associated most with psychosis-behavioral delirium symptoms. CONCLUSIONS:
The results describe in detail the clinical presentation of delirium in patients
undergoing HSCT. Affective distress and fatigue commonly were associated with
delirium. These findings may aid clinicians in improving the recognition and
treatment of delirium in this population and avoiding further morbidity and
potential mortality. Copyright (c) 2005 American Cancer Society.
Fenn, D. and K. George (1999). "Post-stroke mania late in life involving the left
hemisphere.[see comment]." Australian & New Zealand Journal of Psychiatry 33(4):
598-600.
OBJECTIVE: Although post-stroke depression is well recognised, post-stroke
mania has rarely been reported and researched. Most reported cases have
involved lesions of the non-dominant hemisphere. We report a case of late-onset
mania following stroke with a lesion in the dominant hemisphere. CLINICAL
PICTURE: A 78-year-old, right-handed man developed sudden cognitive deficits
and manic symptoms. Investigations revealed lesions in the dominant
hemisphere. TREATMENT: Pharmacological intervention was complicated by
side effects. OUTCOME: His symptoms resolved gradually over 2 months and he
was back to normal in 4 months. CONCLUSIONS: We would encourage further
study in the area of post-stroke mania and especially in relation to the site of the
lesion in the brain.
Fink, M. (2000). "The interaction of delirium and seizures." Seminars in Clinical
Neuropsychiatry 5(2): 93-7.
The induction of a delirium by medical illness, somatic treatments, or
experimental drugs occasionally relieves psychotic, excited, and manic states.
An induced delirium is a feature of modern electroconvulsive therapy (ECT), and
was a feature of insulin coma therapy and psychosurgery. Case material
explores the relationship between psychosis, mania, seizures, and
electroencephalogram. From our understanding of the mechanism of ECT in
relieving intractable status epilepticus, we suggest a hypothesis for the beneficial
interaction between delirium and ECT.
Flacker, J. M. and L. A. Lipsitz (1999). "Neural mechanisms of delirium: current
hypotheses and evolving concepts.[erratum appears in J Gerontol A Biol Sci Med Sci
1999 Jul;54(7):B275]." Journals of Gerontology Series A-Biological Sciences & Medical
Sciences 54(6): B239-46.
The purpose of this article is to review current knowledge regarding potential
neural mechanisms of delirium. A MEDLINE search for relevant English
language articles was undertaken using various combinations of delirium
(including cognitive disorders, encephalopathy, and confusion) with pathogenesis
and pathophysiology. These articles were scanned for content related to
hypotheses concerning the neurobiology of delirium. Additional references were
obtained from a manual search of the bibliography of these articles. A secondary
MEDLINE search of delirium with the mechanism in question (i.e., serotonin,
acetylcholine, etc.) was then undertaken. Literature review was last updated as
of April 1998. Despite being a common problem among elderly patients, the
mechanisms of delirium are poorly understood. Delirium is a syndrome that may
occur as the result of multiple complex interacting neurotransmitter systems and
pathologic processes. The neurotransmitters acetylcholine and serotonin may
play particularly important roles in common medical and surgical delirium. Other
neurotransmitters such as dopamine and gamma-aminobutyric acid each may be
involved in the development of delirium under special conditions. Other
neurobiologic factors such as cytokines, cortisol abnormalities, and oxygen free
radicals will require further study to define their role in delirium. Distinct
neuropathologic processes leading to delirium are beginning to be defined. Such
mechanisms may differ in various clinical settings. There is probably no final
common pathway to delirium, but rather, delirium is the final common symptom of
multiple neurotransmitter abnormalities. Further situation-specific studies of
delirium pathophysiology should lead to more effective prevention and treatment
strategies. [References: 128]
Flacker, J. M. and L. A. Lipsitz (1999). "Serum anticholinergic activity changes with
acute illness in elderly medical patients." Journals of Gerontology Series A-Biological
Sciences & Medical Sciences 54(1): M12-6.
BACKGROUND: Elevated serum anticholinergic activity levels have been
associated with delirium in cross-sectional studies of ill older persons. This study
used serial measures of serum anticholinergic activity levels to determine
whether these levels change following illness resolution, and if such changes are
specific to those with delirium. METHODS: Twenty-two nursing home residents
with a febrile illness had serum specimens drawn and were evaluated for the
presence of delirium during the acute illness and at 1-month follow-up. Delirium
was diagnosed using the Confusion Assessment Method. Serum anticholinergic
activity was determined using a previously described radionuclide competitivebinding assay. RESULTS: Delirium was present during illness in 8 of 22 subjects
(36%), and had resolved by 1-month follow-up in all but one resident. Serum
anticholinergic activity levels were significantly higher during illness than at 1month follow-up in both the delirious (0.69 +/- 0.85 nM atropine equivalents/200
microL sample versus 0.10 +/- 0.16; p =.06) and non-delirious (0.65 +/- 0.51 nM
atropine equivalents/200 microL sample versus 0.08 +/- 0.12; p <.001) groups.
Medication changes did not seem to be related to changes in serum
anticholinergic activity. CONCLUSIONS: In older nursing home residents with a
fever, serum anticholinergic activity appears to be elevated during illness, and
declines following recovery from illness. This effect does not seem to be specific
to those residents with delirium, nor does it seem related to medication changes.
Flacker, J. M. and J. Y. Wei (2001). "Endogenous anticholinergic substances may exist
during acute illness in elderly medical patients." Journals of Gerontology Series ABiological Sciences & Medical Sciences 56(6): M353-5.
BACKGROUND:The purpose of this study was to determine if serum
anticholinergic activity (SACA) arises from endogenous substances produced
during illness. METHODS: Elderly medical inpatients (N = 612) were screened
for anticholinergic medication use in the week prior to the study by interviews of
subjects and proxies and review of emergency room, hospital, and nursing home
medication administration records. Of 24 subjects without a recent anticholinergic
medication history, 15 were recruited and 10 completed the study. Serum
samples were obtained on Day 2 of hospital admission. SACA was measured
using a radionuclide displacement assay. Medications taken by subjects were
assayed for central muscarinic receptor binding at therapeutic concentrations.
Results. Eight of the ten subjects had SACA detectable in the serum. No
medication used by these subjects had anticholinergic activity at usual
therapeutic concentrations. CONCLUSIONS: Endogenous anticholinergic
substances may exist during acute illness. Characterization of such substances
may increase the depth of our understanding of delirium and lead to useful
intervention strategies.
Gagnon, B., P. G. Lawlor, et al. (2001). "The impact of delirium on the circadian
distribution of breakthrough analgesia in advanced cancer patients." Journal of Pain &
Symptom Management 22(4): 826-33.
Most cancer patients will experience pain requiring opioid therapy during their
illness. Standard opioid therapy includes fixed scheduled doses and so-called
"rescue" doses for breakthrough pain. Circadian rhythms seem to influence the
expression of pain and the responsiveness to analgesic medication. Delirium is a
common complication in advanced cancer patients and it also may modify the
expression of pain and the use of analgesic medication. We reviewed the
circadian distribution of breakthrough analgesia (BTA) doses in 104 advanced
cancer patients who were part of a prospective study of the occurrence of
delirium. We found that the circadian distribution of BTA is significantly different
from a random distribution in the case of patients with and without delirium.
Patients without delirium tended to use more BTA (P < 0.001) in the morning,
whereas patients with delirium tended to use more BTA in the evening and at
night (P = 0.02). We conclude that delirium is associated with changes in the
circadian distribution of BTA, which is possibly related to reversal of the normal
circadian rhythm.
Hanley, C. (2004). "Delirium in the acute care setting." MEDSURG Nursing 13(4): 21725.
Older adults are at particular risk for developing delirium, which is often not
recognized by health care providers in the acute care setting. Early recog nition
with a standardized assessment process provides early treatment. Multifactorial
approaches that can be utilized when treating the patient with delirium are
described. [References: 39]
Holschneider, D. P. and A. F. Leuchter (1999). "Clinical neurophysiology using
electroencephalography in geriatric psychiatry: neurobiologic implications and clinical
utility." Journal of Geriatric Psychiatry & Neurology 12(3): 150-64.
Electroencephalography (EEG) offers a unique contribution to the
armamentarium of imaging technologies used in the evaluation of brain function.
The primary clinical application of EEG is in the diagnosis of delirium, dementia,
and epilepsy, which are frequently encountered in the practice of geropsychiatry.
This review summarizes the principles behind generation of the EEG signal, its
strengths and limitations as a technology, clinical indications for performing an
EEG, the principles underlying quantitative EEG (QEEG), and how QEEG is
allowing us to probe brain function and connectivity in new ways. [References:
160]
Horikawa, N., T. Yamazaki, et al. (2003). "Treatment for delirium with risperidone:
results of a prospective open trial with 10 patients." General Hospital Psychiatry 25(4):
289-92.
Delirium is a common psychiatric illness among medically compromised patients.
There is an increasing opportunity to use atypical antipsychotics to treat delirium.
The effects of these drugs on delirium, however, the most appropriate way to use
them, and the associated adverse effects remain unclear. To clarify these points,
a prospective open trial on risperidone was carried out in 10 patients with
delirium. At a low dose of 1.7 mg/d, on average, risperidone was effective in 80%
of patients, and the effect appeared within a few days. There were no serious
adverse effects. However, sleepiness (30%) and mild drug-induced parkinsonism
(10%) were observed; the symptom of sleepiness was a reason for not
increasing the dose. One patient responded to a dose as low as 0.5 mg/d, so it is
recommended that treatment start at a low dose, which may then be increased
gradually. This trial is a preliminary open study with a small sample size, and
further controlled studies will be necessary.
Huffman, J. C. and G. L. Fricchione (2005). "Hypercalcemic delirium associated with
hyperparathyroidism and a vitamin D analog." General Hospital Psychiatry 27(5): 374-6.
Katz, I. R., K. J. Curyto, et al. (2001). "Validating the diagnosis of delirium and
evaluating its association with deterioration over a one-year period." American Journal
of Geriatric Psychiatry 9(2): 148-59.
The authors probed the associations between clinical diagnoses and
independent research measures of cognitive, behavioral, and
electroencephalographic (EEG) changes in hospitalized older patients and
investigated the contribution of medical illness to deterioration. Patients (N=96;
47 of whom were hospitalized during the course of 1 year; 12 diagnosed with
delirium) received tests of cognitive and physical functioning and the Cumulative
Illness Rating Scale, specific neuropsychological tests, and a two-channel EEG.
Delirium was associated with independent measures of cognitive decline and
EEG slowing. Hospitalization was associated with deterioration in functional
status during the year, whether or not patients showed delirium. Results suggest
that medical illness leading to hospitalization can contribute significantly to
deterioration in self-care, and, when it is associated with delirium, to deterioration
in cognitive performance and cerebral activity over a period of 1 year.
Koponen, H. J. (1999). "Neurochemistry and delirium." Dementia & Geriatric Cognitive
Disorders 10(5): 339-41.
Acute confusional state or delirium is one of the most common organic brain
syndromes especially in the elderly. It develops suddenly, within hours or days,
and often during a period of hospitalization. In this paper we review the results of
our studies on the neurochemistry of delirium.
Lewis, M. C. and S. R. Barnett (2004). "Postoperative delirium: the tryptophan
dyregulation model." Medical Hypotheses 63(3): 402-6.
A model previously presented by Uchida in this journal [Med. Hypotheses 53
(1997) 103] described a mechanism for postoperative delirium. It described an
increased level of melatonin resulting in a central "serotonin shortage". This
construct adequately explained only the hypoactive type of delirium. Recently it
has been shown that a reduction in urinary metabolites of melatonin is
associated with hyperactive delirium, whereas urinary metabolites were
increased in the hypoactive variant. These findings suggest that this initial
paradigm requires modification. We propose that both the agitation seen in
hyperactive delirium, and the somnolence associated with the hypoactive form
could be explained by a disturbance of central tryptophan homeostasis. It is
postulated that intervention in the form of melatonin administration may restore
tryptophan levels, and prevent delirium. Copyright 2004 Elsevier Ltd.
Litton, K. A. (2003). "Delirium in the critical care patient: what the professional staff
needs to know." Critical Care Nursing Quarterly 26(3): 208-13.
Delirium has been recognized in the literature as a significant problem in the care
and treatment of the critical care patient. Delirium, a medical disorder that results
in the morbidity and mortality of the patients, especially in the elderly, is often
misdiagnosed and inappropriately treated. Nurses and other health care
professionals need in-depth education about delirium, validated and
understandable assessment tools, and astute clinical observational skills. A
comprehensive and aggressive clinical management plan that incorporates
appropriate pharmacological agents will result in less morbidity and improved
long-term outcomes. [References: 9]
Mackenzie Ross, S. (2000). "Profound retrograde amnesia following mild head injury:
organic or functional?" Cortex 36(4): 521-37.
This paper describes a 56 year old female patient (JJ) who suffered a minor head
injury at work and presented with profound retrograde amnesia for both public
events and autobiographical material spanning her entire life. In addition, she
complained of word-finding difficulties and anterograde memory impairment and
neuropsychological assessment found evidence of mild executive dysfunction.
Neurological investigations (CT and EEG) were essentially normal although
changes indicative of small vessel disease were noted on MRI brain scan.
Various forms and aetiologies of remote memory loss were considered including,
simulated, psychogenic and organic amnesia, but differential diagnosis proved
difficult. It is proposed that criteria used in clinical practice to differentiate
functional and organic complaints are limited and this may be because (1) both
factors can be involved in the aetiology of amnesia, and (2) a similar underlying
brain mechanism, such as a retrieval deficit could underlie many instances of
organic and psychogenic amnesia. Future research, complemented by functional
brain imaging, is needed to explore the nature of retrieval deficits.
Marcantonio, E., T. Ta, et al. (2002). "Delirium severity and psychomotor types: their
relationship with outcomes after hip fracture repair." Journal of the American Geriatrics
Society 50(5): 850-7.
OBJECTIVES: To validate the Memorial Delirium Assessment Scale (MDAS) as
a measure of delirium severity in a cohort of patients aged 65 and older; to
examine the association between severity of delirium and patient outcomes; and
to examine the association between psychomotor variants of delirium and each
of those outcomes. DESIGN: Prospective assessment of sample. SETTING:
Hospital. PARTICIPANTS: One hundred twenty-two older patients (mean age +/standard deviation = 79 +/- 8) who had undergone acute hip fracture surgery.
MEASUREMENTS: We used standardized instruments to assess prefracture
activities of daily living (ADLs), ambulatory status, cognition, and living situation.
Postoperatively, each patient was interviewed daily. Delirium was diagnosed
using the Confusion Assessment Method (CAM), and delirium severity was
measured using the MDAS. The MDAS was also used to categorize the
psychomotor types of delirium into "purely hypoactive" or "any hyperactivity."
Telephone or face-to-face interviews were conducted at 1 and 6 months to
assess survival, ADL function, ambulatory status, and living situation. RESULTS:
Of 122 patients, 40% developed CAM-defined delirium. Delirious patients had
higher average MDAS scores than nondelirious patients (11.7 vs 2.4, P <.0001).
We used the median of the average MDAS score to classify patients into mild or
severe delirium. Severe delirium was generally associated with worse outcomes
than was mild delirium, and the associations reached statistical significance for
nursing home placement or death at 6 months (52% vs 17%, P =.009).
Additionally, patients who did not meet full CAM criteria for delirium experienced
worse outcomes if they had some symptoms of delirium than if they had no or
few symptoms (nursing home placement or death at 6 months: 27% vs 0%, P
=.001). Surprisingly, these patients with subsyndromal delirium who did not fulfill
CAM criteria for delirium but demonstrated significant delirium symptoms, had
outcomes similar to or worse than those with mild CAM-defined delirium. Pure
hypoactive delirium accounted for 71% (34/48) of cases and was less severe
than was delirium with any hyperactivity (average MDAS score 10.6 vs 14.8, P
=.007). In our cohort, patients with pure hypoactive delirium had better outcomes
than did those with any hyperactivity (nursing home placement or death at 1
month: 32% vs 79%, P =.003); this difference persisted after adjusting for
severity. CONCLUSION: In this study of delirium in older hip fracture patients,
the MDAS, a continuous severity measure, was a useful adjunct to the CAM, a
dichotomous diagnostic measure. In patients with CAM-defined delirium, severe
delirium was generally associated with worse outcomes than was mild delirium.
In patients who did not fulfill CAM criteria, subsyndromal delirium was associated
with worse outcomes than having few or no symptoms of delirium. Patients with
subsyndromal delirium had outcomes similar to patients with mild delirium,
suggesting that a dichotomous approach to diagnosis and management may be
inappropriate. Pure hypoactive delirium was more common than delirium with
any hyperactive features, tended to be milder, and was associated with better
outcomes even after adjusting for severity. Future studies should confirm our
preliminary associations and examine whether treatment to reduce the severity of
delirium symptoms can improve outcomes after hip fracture repair.
Marcantonio, E. R., S. E. Simon, et al. (2003). "Delirium symptoms in post-acute care:
prevalent, persistent, and associated with poor functional recovery." Journal of the
American Geriatrics Society 51(1): 4-9.
OBJECTIVES: To determine the prevalence of delirium symptoms at the time of
admission to post-acute facilities, the persistence of delirium symptoms in this
setting, and the association of delirium symptoms with functional recovery.
DESIGN: Prospective cohort study. SETTING: Eighty-five post-acute care
facilities: 55 rehabilitation hospitals and 30 skilled nursing facilities in 29 states.
PARTICIPANTS: Five hundred fifty-one consenting patients aged 65 and older
newly admitted to participating facilities from acute care hospitals.
MEASUREMENTS: Data were collected as part of a field study effort related to
the Minimum Data Set (MDS). Basic demographic data, medical comorbidity,
delirium symptoms, and functional status--activities of daily living (ADLs) and
instrumental activities of daily living (IADLs)--were obtained from MDS
assessments performed within 4 days of admission and again 1 week later by the
patient's primary nurse. Six delirium symptoms (easily distracted, periods of
altered perception, disorganized speech, periods of restlessness, periods of
lethargy, and mental function varies over the course of a day) were assessed
after appropriate training. RESULTS: Of the 551 patients (mean age +/- standard
deviation 78 +/- 7, 64% women), 126 had delirium symptoms on post-acute
admission, for an overall prevalence of 23%. In patients with delirium symptoms
on the admission assessment, 1 week later, 14% had completely resolved, 22%
had fewer delirium symptoms, 52% had the same number of symptoms, and
12% had more symptoms. Of those with no delirium symptoms on admission, 4%
had new symptoms 1 week later. Patients who had the same number of or more
delirium symptoms at the second assessment had significantly worse ADL and
IADL recovery than those with fewer or resolved delirium symptoms or those with
no delirium symptoms at either assessment. Persistent delirium symptoms
remained significantly associated with worse ADL and IADL recovery after
adjusting for age, comorbidity, dementia, and baseline functional status.
CONCLUSIONS: The data from this study provide strong preliminary evidence
that, in patients newly admitted to post-acute care facilities from acute care
hospitals, delirium symptoms are prevalent, persistent, and associated with poor
functional recovery. Educational efforts are warranted to help post-acute facility
staff recognize and manage this common and morbid condition.
Marshall, M. C. and M. D. Soucy (2003). "Delirium in the intensive care unit." Critical
Care Nursing Quarterly 26(3): 172-8.
Delirium in the intensive care unit (ICU) is a complex, common, and problematic
condition that interferes with healing and recovery. It leads to higher morbidity
and mortality and extended hospital stays. The aging population older than 65,
and more likely to develop delirium, is the fastest growing population in the
United States and is increasingly seen in the ICU. Delirium is often unrecognized
and misdiagnosed, which leads to mistreatment or lack of appropriate treatment.
This article discusses the definition of delirium, pathogenesis, clinical practice
guidelines, newer assessment tools for ICU, and nursing interventions directed
toward prevention and early identification of delirium. [References: 30]
McCusker, J., M. Cole, et al. (2003). "The course of delirium in older medical inpatients:
a prospective study.[see comment]." Journal of General Internal Medicine 18(9): 696704.
OBJECTIVES: To describe the clinical course and outcomes of delirium up to 12
months after diagnosis, the relationship between the in-hospital clinical course
and post-discharge outcomes, and the role of dementia in both the clinical course
and outcomes of delirium. DESIGN: Prospective cohort study. SETTING: Medical
wards of a 400-bed, university-affiliated, primary acute care hospital in Montreal.
PATIENTS: Cohort of 193 medical inpatients aged 65 and over with delirium
diagnosed at admission or during the first week in hospital, who were discharged
alive from hospital. MEASUREMENTS AND MAIN RESULTS: Study outcomes
included cognitive impairment and activities of daily living (standardized, face-toface clinical instruments at 1-, 2-, 6-, and 12-month follow-up), and mortality.
Dementia, severity of illness, comorbidity, and sociodemographic variables were
measured at time of diagnosis. Several measures of the in-hospital course of
delirium were constructed. The mean numbers of symptoms of delirium at
diagnosis and 12-month follow-up, respectively, were 4.5 and 3.5 in the subgroup
of patients with dementia and 3.4 and 2.2 among those without dementia.
Inattention, disorientation, and impaired memory were the most persistent
symptoms in both subgroups. In multivariate analyses, pre-morbid and admission
level of function, nursing home residence, and slower recovery during the initial
hospitalization were associated with worse cognitive and functional outcomes but
not mortality. CONCLUSIONS: Among patients with and without dementia,
symptoms of delirium persist up to 12 months after diagnosis. Quicker in-hospital
recovery is associated with better outcomes.
Meagher, D. (2001). "Delirium episode as a sign of undetected dementia among
community dwelling elderly subjects." Journal of Neurology, Neurosurgery & Psychiatry
70(6): 821.
Meagher, D. J. and P. T. Trzepacz (2000). "Motoric subtypes of delirium." Seminars in
Clinical Neuropsychiatry 5(2): 75-85.
Delirium is a common neuropsychiatric disorder with wide ranging symptoms and
significant morbid impact. Disturbances of motor behavior are an important
feature of delirium and form the basis for the most commonly studied clinical
subtype. This article reviews the relevance of motoric disturbance to delirium
phenomenology and discusses possible neurobiological causes for different
presentations of motor behavior in delirium. Evidence is presented to support the
usefulness of using motorically defined subtypes based on identified differences
according to underlying origins, pathophysiologies, responsiveness to therapy
and natural course. Methodological issues relating to motoric subtype studies are
addressed and suggestions for future research are made. [References: 79]
Mellers, J. D., B. K. Toone, et al. (2000). "A neuropsychological comparison of
schizophrenia and schizophrenia-like psychosis of epilepsy." Psychological Medicine
30(2): 325-35.
BACKGROUND: The schizophrenia-like psychoses of epilepsy (SLPE) might
represent a secondary form of schizophrenia in which the pathology is relatively
confined to the temporal lobe. To test this possibility we have compared the
neuropsychological profile of schizophrenia and SLPE. Our main hypothesis was
that both psychotic groups would show deficits of temporal lobe function but that
prefrontal impairment, as measured by tests of executive function, would be
found only in the primary schi ophrenic group. METHODS: Four groups were
studied: (1) patients with SLPE (N = 25); (2) patients with epilepsy but not
psychiatric history (N = 24); (3) patients with schizophrenia (N = 22); and (4)
healthy volunteers (N = 24). Neuropsychological testing comprised measures of
pre-morbid IQ, current verbal and performance IQ, information processing, digit
span, motor speed, verbal and visual learning and memory, verbal fluency, the
Wisconsin Card Sorting Task, the Stroop test and the trail making task.
RESULTS: Patients with schizophrenia and those with SLPE had almost identical
neuropsychological profiles, with impairments of attention, episodic memory
(verbal > visual) and executive function. The epileptic controls showed similar
though less severe impairments of memory and of some tests of executive
function. CONCLUSIONS: Our results do not support the hypothesis that the
pathophysiology of SLPE and schizophrenia are distinct. While our findings
suggest an important role for dominant temporal lobe abnormality in
schizophrenia, both in its primary form and in that occurring in patients with
epilepsy, they also implicate generalized cognitive impairment, manifest in
particular as attentional deficits, in both forms of the disorder.
Mendez, M. F., T. Chow, et al. (2000). "Pedophilia and temporal lobe disturbances."
Journal of Neuropsychiatry & Clinical Neurosciences 12(1): 71-6.
Paraphilias may occur with brain disease, but the nature of this relationship is
unclear. The authors report 2 patients with late-life homosexual pedophilia. The
first met criteria for frontotemporal dementia; the second had bilateral
hippocampal sclerosis. Both were professional men with recent increases in
sexual behavior. In both, 18-fluorodeoxyglucose positron emission tomography
revealed prominent right temporal lobe hypometabolism. These cases and the
literature suggest that bilateral anterior temporal disease affecting right more
than left temporal lobe can increase sexual interest. A predisposition to
pedophilia may be unmasked by hypersexuality from brain disease. These
observations have potential implications for all neurologically based paraphilias.
Moore, A. R. and S. T. O'Keeffe (1999). "Drug-induced cognitive impairment in the
elderly." Drugs & Aging 15(1): 15-28.
Elderly people are more likely than younger patients to develop cognitive
impairment as a result of taking medications. This reflects age- and diseaseassociated changes in brain neurochemistry and drug handling. Delirium (acute
confusional state) is the cognitive disturbance most clearly associated with drug
toxicity, but dementia has also been reported. The aetiology of cognitive
impairment is commonly multifactorial, and it may be difficult to firmly establish a
causal role for an individual medication. In studies of elderly hospital patients,
drugs have been reported as the cause of delirium in 11 to 30% of cases.
Medication toxicity occurs in 2 to 12% of patients presenting with suspected
dementia. In some cases CNS toxicity occurs in a dose-dependent manner, often
as a result of interference with neurotransmitter function. Drug-induced delirium
can also occur as an idiosyncratic complication. Finally, delirium may occur
secondary to iatrogenic complications of drug use. Almost any drug can cause
delirium, especially in a vulnerable patient. Impaired cholinergic
neurotransmission has been implicated in the pathogenesis of delirium and of
Alzheimer's disease. Anticholinergic medications are important causes of acute
and chronic confusional states. Nevertheless, polypharmacy with anticholinergic
compounds is common, especially in nursing home residents. Recent studies
have suggested that the total burden of anticholinergic drugs may determine
development of delirium rather than any single agent. Also, anticholinergic effects
have been identified in many drugs other than those classically thought of as
having major anticholinergic effects. Psychoactive drugs are important causes of
delirium. Narcotic agents are among the most important causes of delirium in
postoperative patients. Long-acting benzodiazepines are the commonest drugs
to cause or exacerbate dementia. Delirium was a major complication of treatment
with tricyclic antidepressants but seems less common with newer agents.
Anticonvulsants can cause delirium and dementia. Drug-induced confusion with
nonpsychoactive drugs is often idiosyncratic in nature, and the diagnosis is easily
missed unless clinicians maintain a high index of suspicion. Histamine H2
receptor antagonists, cardiac medications such as digoxin and beta-blockers,
corticosteroids, non-steroidal anti-inflammatory agents and antibiotics can all
cause acute, and, less commonly, chronic confusion. Drug-induced confusion
can be prevented by avoiding polypharmacy and adhering to the saying 'start low
and go slow'. Special care is needed when prescribing for people with cognitive
impairment. Early diagnosis of drug-induced confusion, and withdrawal of the
offending agent or agents is essential. [References: 123]
Mussi, C., R. Ferrari, et al. (1999). "Importance of serum anticholinergic activity in the
assessment of elderly patients with delirium." Journal of Geriatric Psychiatry &
Neurology 12(2): 82-6.
To evaluate the importance of serum anticholinergic activity (SAA) in elderly
patients who developed delirium following hospital admission, we performed a
cross-sectional study with consecutively referred inpatients in a university
geriatric medical ward. Sixty-one patients aged 66 to 95 years (mean age:
79.2+/-11.6; 54% females) were recruited. Delirium was assessed by means of
the Confusion Assessment Method, SAA determination, questionnaire for current
drug treatment, past medical history and clinical examination, and blood
chemistries. Patients were divided into two groups according to the absence (N =
49) or the presence (N = 12) of delirium. Delirious patients showed a significantly
higher SAA (23.0 vs 3.9 pmol/mL atropine equivalents, P <.004); they were using
antibiotics (P <.05), neuroleptics (P <.002), barbiturates (P <.004), and
benzodiazepines (P <.005) more frequently. Subjects with delirium were more
likely to have infections and a lower Body Mass Index; they had higher plasma
glucose and creatinine. The multivariate analysis identified SAA and use of
neuroleptics, and benzodiazepines as the most important features independently
associated with delirium. SAA may be a suitable marker for identifying people at
risk of developing delirium. Moreover, neuroleptics and benzodiazepines must be
carefully used in the elderly because of their relationship with the onset of
delirium.
Nakamura, J., R. Yoshimura, et al. (2001). "Association of plasma free-3-methoxy-4hydroxyphenyl (ethylene)glycol, natural killer cell activity and delirium in postoperative
patients." International Clinical Psychopharmacology 16(6): 339-43.
We measured and compared levels of plasma free 3-methoxy-4-hydroxyphenyl
(ethylene)glycol (pMHPG), a major metabolite of noradrenaline, and natural killer
(NK) cell activity in 26 patients prior to their undergoing an operation for
cardiovascular diseases; 11 of whom expressed delirium and 15 who did not. In
conclusion, we found that pMHPG levels before an operation were higher in
patients with postoperative delirium than in the patients without, while NK cell
activity showed no difference between the two groups. It is possible that
hyperactivity of noradrenargic neurons is connected with the development of
postoperative delirium. Furthermore, we considered that measurement of
pMHPG level before operation might be a useful tool to predict the occurrence of
postoperative delirium.
Northington, W. and A. Yates "Caring for the aged. The pathophysiology of aging & its
significant implications for prehospital care." Journal of Emergency Medical Services
30(7): 70-9.
O'Keeffe, S. T. and J. N. Lavan (1999). "Clinical significance of delirium subtypes in
older people." Age & Ageing 28(2): 115-9.
OBJECTIVE: to examine the relative frequency and outcome of clinical subtypes
of delirium in older hospital patients. DESIGN: prospective observational study.
SETTING: acute geriatric unit in a teaching hospital. SUBJECTS: 94 patients
with delirium from a prospective study of 225 admissions. MEASUREMENTS:
clinical subtypes of delirium were determined according to predefined criteria.
Characteristics examined in these subgroups included illness severity on
admission, prior cognitive impairment, mortality, duration of hospital stay and
hospital-acquired complications. RESULTS: of the 94 patients, 20 (21%) had a
hyperactive delirium, 27 (29%) had a hypoactive delirium, 40 (43%) had a mixed
hypoactive-hyperactive psychomotor pattern and seven (7%) had no
psychomotor disturbance. There were significant differences between the four
groups in illness severity (P < 0.05), length of hospital stay (P < 0.005) and
frequency of falls (P < 0.05). Patients with hypoactive delirium were sicker on
admission, had the longest hospital stay and were most likely to develop
pressure sores. Patients with hyperactive delirium were most likely to fall in
hospital. There were no differences in aetiological factors between the groups.
CONCLUSION: outcomes of hospitalization differ in different clinical subtypes of
delirium.
O'Keeffee, S. T. (1999). "Delirium in the elderly." Age & Ageing 28 Suppl 2: 5-8.
Olin, K., M. Eriksdotter-Jonhagen, et al. (2005). "Postoperative delirium in elderly
patients after major abdominal surgery." British Journal of Surgery 92(12): 1559-64.
BACKGROUND: The aim of this study was to investigate the occurrence of
postoperative delirium (POD) in elderly patients undergoing major abdominal
surgery and to identify factors associated with delirium in this population.
METHODS: Data were collected prospectively from 51 patients aged 65 years or
more. Delirium was diagnosed by the Confusion Assessment Method and from
the medical records. The Mini Mental State Examination (MMSE) was used to
identify cognitive impairment. RESULTS: POD occurred in 26 of 51 patients.
Delirium lasted for 1-2 days in 14 patients (short POD group) and 3 days or more
in 12 patients (long POD group). The latter patients had significantly greater
intraoperative blood loss and intravenous fluid infusion, a higher rate of
postoperative complications, a lower MMSE score on postoperative day 4 and a
longer hospital stay than patients without POD. Patients in the short POD group
were significantly older than those in the long POD group and those who did not
develop delirium. CONCLUSION: Approximately half of the elderly patients in this
study developed POD. Bleeding was found to be an important risk factor for
delirium. Copyright (c) 2005 British Journal of Surgery Society Ltd. Published by
John Wiley & Sons, Ltd.
Olsson, T. (1999). "Activity in the hypothalamic-pituitary-adrenal axis and delirium."
Dementia & Geriatric Cognitive Disorders 10(5): 345-9.
Glucocorticoid hormones are important for coping with stress but may have
deleterious effects on mood and memory during prolonged excessive secretion.
A key abnormality related to cortisol excess in delirium seems to be abnormal
'shut-off' of the hypothalamic-pituitary-adrenal (HPA) axis tested by the
dexamethasone suppression test. In experimental models, the hippocampal
formation is of prime importance for normal HPA axis shut-off. In this brain area,
a close interaction between neurotransmittors, notably acetylcholine, serotonin
and noradrenaline, and glucocorticoid receptors, is present and possibly relevant
for the development of delirium in elderly patients with stroke and
neurodegenerative brain diseases. [References: 46]
Paulsen, J. S., R. E. Ready, et al. (2001). "Neuropsychiatric aspects of Huntington's
disease." Journal of Neurology, Neurosurgery & Psychiatry 71(3): 310-4.
OBJECTIVE: Neuropsychiatric symptoms are common in Huntington's disease
and have been considered its presenting manifestation. Research characterising
these symptoms in Huntington's disease is variable, however, encumbered by
limitations within and across studies. Gaining a better understanding of
neuropsychiatric symptoms is essential, as these symptoms have implications for
disease management, prognosis, and quality of life for patients and caregivers.
METHOD: Fifty two patients with Huntington's disease were administered
standardised measures of cognition, psychiatric symptoms, and motor
abnormalities. Patient caregivers were administered the neuropsychiatric
inventory. RESULTS: Ninety eight per cent of the patients exhibited
neuropsychiatric symptoms, the most prevalent being dysphoria, agitation,
irritability, apathy, and anxiety. Symptoms ranged from mild to severe and were
unrelated to dementia and chorea. CONCLUSIONS: Neuropsychiatric symptoms
are prevalent in Huntington's disease and are relatively independent of cognitive
and motor aspects of the disease. Hypothesised links between neuropsychiatric
symptoms of Huntington's disease and frontal-striatal circuitry were explored.
Findings indicate that dimensional measures of neuropsychiatric symptoms are
essential to capture the full range of pathology in Huntington's disease and are
vital to include in a comprehensive assessment of the disease.
Pratico, C., D. Quattrone, et al. (2005). "Drugs of anesthesia acting on central
cholinergic system may cause post-operative cognitive dysfunction and delirium."
Medical Hypotheses 65(5): 972-82.
Given the progressive and constant increase of average life expectancy, an
increasing number of elderly patients undergo surgery. After surgery, elderly
patients often exhibit a transient reversible state of cerebral cognitive alterations.
Among these cognitive dysfunctions, a state of delirium may develop. Delirium is
an aetiologically non-specific syndrome characterised by concurrent disturbances
of consciousness and attention, perception, thinking, memory, psychomotor
behaviour and the sleep-wake cycle. Delirium appears to occur in 10-26% of
general medical patients over 65, and is frequently associated with a significant
increase in morbidity and mortality. During hospitalization, mortality rates have
been estimated to be 10-26% of patients who developed post-operative delirium,
and 22-76% during the following months. Over the last few decades, postoperative delirium has been associated with several pre-operative predictor
factors, as well as age (50 years and older), alcohol abuse, poor cognitive and
functional status, electrolyses or glucose abnormalities, and type of surgery. The
uncertain pathogenesis of post-operative cognitive dysfunctions and delirium has
not permitted a causal approach to developing an effective treatment. General
anesthesia affects brain function at all levels, including neuronal membranes,
receptors, ion channels, neurotransmitters, cerebral blood flow and metabolism.
The functional equivalents of these impairments involve mood, memory, and
motor function behavioural changes. These dysfunctions are much more evident
in the occurrence of stress-regulating transmission and in the alteration of intracellular signal transduction systems. In addition, more essential cellular
processes, that play an important role in neurotransmitter synthesis and release,
such as intra-neuronal signal transduction and second messenger system, may
be altered. Keeping in mind the functions of the central muscarinic cholinergic
system and its multiple interactions with drugs of anesthesia, it seems possible to
hypothesize that the inhibition of muscarinic cholinergic receptors could have a
pivotal role in the pathogenesis not only of post-operative delirium but also the
more complex phenomena of post-operative cognitive dysfunction.
Rahkonen, T., R. Luukkainen-Markkula, et al. (2000). "Delirium episode as a sign of
undetected dementia among community dwelling elderly subjects: a 2 year follow up
study." Journal of Neurology, Neurosurgery & Psychiatry 69(4): 519-21.
Cognitive decline is commonly stated as one of the main risk factors for delirium.
The aim was to assess the importance of a delirium episode as a symptom of an
underlying dementia among community dwelling healthy elderly people in a
prospective 2 year follow up study. The study patients consisted of 51 people
living at home and older than 65 years of age, without severe underlying
disorders including diagnosed dementia, admitted consecutively as emergency
cases to hospital because of an acute delirious state and followed up for 2 years.
The diagnosis of delirium and dementia were based on the DSM-III-R criteria.
The community dwelling patients were evaluated and tested annually by a clinical
investigator, a geriatric study nurse, and a neuropsychologist. The medical
records of the institutionalised patients were also evaluated. Dementia was
diagnosed immediately after the assurance that delirium symptoms had subsided
in 14 out of 51 subjects (27%) and the additional 14 subjects were diagnosed as
being demented during the 2 year follow up, 28 out of 51 patients (55%)
altogether. Alzheimer's disease or mixed dementia was diagnosed in 14 out of 51
patients (27%), vascular dementia in 10 (20%), and dementia with Lewy bodies
in two (4%). One case of alcoholic dementia and one case of a non-alcoholic
hepatic encephalopathia were also found. A delirium episode is often the first
sign of dementia requiring attention from medical and social professionals.
Reischies, F. M., A. H. Neuhaus, et al. (2005). "Electrophysiological and
neuropsychological analysis of a delirious state: the role of the anterior cingulate gyrus."
Psychiatry Research 138(2): 171-81.
Functional neuroimaging studies in humans have provided evidence that a frontal
network including the anterior cingulate cortex (ACC) plays an important role in
attention and awareness. Disturbed attention and awareness are core symptoms
of delirium, but imaging studies of attentional dysfunctions in delirium are lacking.
However, an increase of slow electroencephalographic (EEG) activity (delta,
theta) is a consistent biological finding in delirium. The question whether this slow
activity is related to a disturbance in the frontal attentional network has not yet
been addressed. The delirium after electroconvulsive therapy (ECT) has been
investigated using 32-channel resting EEG before and shortly after ECT in 12
patients with major depressive disorder. During delirium compared with baseline
studies, substantial increases of delta and theta power and a decrease of alpha
power were observed. The decrease of theta activity at the Fz electrode position
in the following 24 h was significantly related to the recovery of awareness and
performance of free recall. Source analysis with Low Resolution Electromagnetic
Tomography (LORETA) indicated that the main generators of the theta excess
during delirium were significantly localized in the anterior cingulate cortex, and
additionally in right fronto-temporal brain areas. The results support the concept
that a disturbance of attention and awareness during delirium is related to a
dysfunction of an attentional network involving the ACC. However, the
localization of the theta excess may reflect some motor dysfunctions as well. This
dysfunction of the ACC was shown for the first time in patients during a delirious
state and may represent an important pathophysiological aspect of delirium.
Robertsson, B., K. Blennow, et al. (2001). "Hyperactivity in the hypothalamic-pituitaryadrenal axis in demented patients with delirium." International Clinical
Psychopharmacology 16(1): 39-47.
Occurrence of delirium is known to be related to, among other things, organic
brain disorder, somatic disease and old age. It has been hypothesized that
delirium is also associated with stress. Disturbances of the hypothalamicpituitary-adrenal (HPA) system have been found in delirious patients in various
studies. The aim of the present study was to determine the activity in the HPA
axis in demented patients to ascertain whether the stress regulating system was
more disturbed in patients with delirium than in those without delirium. Demented
inpatients with no acute medical illness were included in the study. Basal cortisol
levels in serum were measured and dexamethasone suppression test (DST) was
performed. The most important finding of the study was a strong relationship
between delirium and DST pathology irrespective of age and severity of
dementia. It is suggested that certain demented individuals have an impaired
HPA system and a low delirium threshold and respond to stress with delirium.
Samuels, S. C. and M. M. Evers (2002). "Delirium. Pragmatic guidance for managing a
common, confounding, and sometimes lethal condition." Geriatrics 57(6): 33-8; quiz 40.
Virtually any medical illness, intoxication, or medication can precipitate delirium,
an acute confusional state common among older persons. Delirium is associated
with a high risk of morbidity and mortality, thus management requires thorough
assessment and swift but careful action. A range of nonpharmacologic
interventions can aid management of delirium, but in general, emergent, empiric
pharmacotherapy is indicated for acute cases. Key to assessment and diagnosis
is ruling out dementia and depression, determining the presence of delirium, and
establishing an underlying cause. Several screening tools are available to aid this
effort. Vigilance can help reduce the high number of patients discharged with
unresolved symptoms.
Sandberg, O., Y. Gustafson, et al. (1999). "Clinical profile of delirium in older
patients.[see comment]." Journal of the American Geriatrics Society 47(11): 1300-6.
OBJECTIVE: To examine the prevalence, psychiatric and behavior symptoms,
differing symptom profiles, and diurnal variations of delirium in older patients.
DESIGN: A descriptive, point prevalence study with a cross-sectional design.
SETTING: One ordinary county hospital (n = 148), three nursing homes (n =
202), five old people's homes (n = 196), and home medical care patients (n =
171) in parts of a hospital catchment area in Mid-Sweden. PARTICIPANTS: A
total of 717 patients 75 years of age and older were observed and assessed for
the prevalence of delirium. Women accounted for 66.4% of the studied
population, and the mean age for both sexes was 83.7 years.
MEASUREMENTS: All patients were examined using the OBS (Organic Brain
Syndrome) scale, and delirium was diagnosed according to DSM-III-R.
RESULTS: Delirium was diagnosed in 315 of 717 (43.9%) patients, and 135 of
315 (42.9%) of the delirious patients had dementia. Thirty-seven percent of the
patients with delirium were delirious in the afternoon, evening, or at night, and
47% of the delirious patients had morning delirium. The delirious patients
presented a wide variety of psychiatric symptoms. More than half the patients
exhibiting anxiety, psychomotor slowing, depressed mood, and irritability. Nearly
26% were classified as having hypoactive, 22% as having hyperactive, and 42%
as having mixed delirium, whereas 11% had neither hypo- nor hyperactive
delirium. Seventy-seven percent were classified as having delirium with
pronounced emotional and 43% with pronounced psychotic symptoms.
CONCLUSIONS: This study shows that patients with delirium have very different
clinical profiles. This might indicate a need for different treatment strategies for
patients with different types of delirium.
Shenal, B. V., R. D. Rhodes, et al. (2001). "Quantitative electroencephalography
(QEEG) and neuropsychological syndrome analysis." Neuropsychology Review 11(1):
31-44.
The ideographic, syndrome analysis and the nomothetic, standardized test
battery approaches to neuropsychological assessment are compared and
contrasted within the context of advances in noninvasive technology readily
available for use within the examiner's office. By demonstrating the relative
strengths and benefits of syndrome analysis, it is suggested that this approach
provides a thorough and efficient method of neuropsychological assessment.
Subsequently, the utility of an a priori hypothesis testing process approach as a
critical technique in syndrome analysis will be supported. It will be proposed that
QEEG procedures provide a useful method for further substantiating conclusions
generated from a syndrome analysis approach to neuropsychological
assessment. Two cases are described demonstrating the utility and flexibility of
the QEEG as a confirmatory test of localization following syndrome analysis. In
summary, the contributions that neuropsychologists make to the understanding
of brain-behavior relationships may be strengthened by combining
neuropsychological and neurophysiological assessment methods.
Tavcar, R., M. Z. Dernovsek, et al. (1999). "Ketoprofen intoxication delirium." Journal of
Clinical Psychopharmacology 19(1): 95-6.
Tune, L. E. (2000). "Serum anticholinergic activity levels and delirium in the elderly."
Seminars in Clinical Neuropsychiatry 5(2): 149-53.
This article will briefly review the clinical studies focusing on measurement of
serum levels of anticholinergic activity in delirious states. Three experimental
approaches have been taken. First, to identify medications currently prescribed
that have subtle anticholinergic effects. The current "list" includes 48 commonly
prescribed medications. Second, to associate serum anticholinergic activity with
delirium in various clinical states including postcardiotomy delirium,
postelectroconvulsive delirium, delirious elderly medical inpatients, and nursing
home patients. Third, to intervene in patients with elevated anticholinergic activity
by reducing known anticholinergics and correlating this reduction with clinical
measures of cognition and delirium. Our most recent data investigate the impact
of anticholinergics on demented patients. Prevalence of delirium was significantly
higher in patients receiving larger numbers of anticholinergics. [References: 25]
Tune, L. E. and S. Egeli (1999). "Acetylcholine and delirium." Dementia & Geriatric
Cognitive Disorders 10(5): 342-4.
The neurotransmitter acetylcholine has been implicated in animal and human
studies of delirium. This chapter will briefly review the clinical studies focussing
on measurement of serum levels of anticholinergic activity in delirious states.
Three approaches have been taken. First, to identify medications currently
prescribed that have subtle anticholinergic effects. The current 'list' includes 48
commonly prescribed medications. Second, to associate serum anticholinergic
activity with delirium in various clinical states including postcardiotomy delirium,
postelectroconvulsive delirium, delirious elderly medical inpatients, and nursing
home patients. Third, to intervene in patients with elevated anticholinergic activity
by reducing known anticholinergics and correlating this reduction with clinical
measures of cognition and delirium. Our most recent data investigates the impact
of anticholinergics on demented patients. Rates of delirium were significantly
higher in patients receiving larger numbers of anticholinergics. [References: 9]
van der Mast, R. C. (1999). "Postoperative delirium." Dementia & Geriatric Cognitive
Disorders 10(5): 401-5.
This article reviews the incidence, pathophysiological hypotheses, and etiology of
postoperative delirium, especially in the elderly. Preoperative, intraoperative, and
postoperative risk factors for delirium following surgery are discussed. Results of
various studies on postoperative delirium appear hardly comparable due to
methodological and population differences. Therefore, it is difficult to draw any
conclusions on postoperative delirium in general. Special attention is paid to
delirium after cardiac surgery since this syndrome has been studied most.
[References: 28]
van der Mast, R. C. and D. Fekkes (2000). "Serotonin and amino acids: partners in
delirium pathophysiology?" Seminars in Clinical Neuropsychiatry 5(2): 125-31.
Delirium may be the result of dysfunction of multiple interacting neurotransmitter
systems. Changes in the levels of various amino acids being precursors of
cerebral neurotransmitters may affect their function and, thus, contribute to the
development of delirium. Serotonin is one of the neurotransmitters that may play
an important role in medical and surgical delirium. Normal serotonin synthesis
and release in the human brain is, among others, dependent on the availability of
its precursor tryptophan (Trp) from blood. The essential amino acid Trp competes
with the other large neutral amino acids (LNAA) tyrosine, phenylalanine, valine,
leucine, and isoleucine for transport across the blood-brain barrier. This
competition determines its uptake into the brain, represented by the ratio of the
plasma level of Trp to the sum of the other LNAA. The plasma ratio of Trp/LNAA,
plasma level of Trp, and serotonin in plasma and platelets have been used as
indirect peripheral measures for central serotonergic functioning. Both increased
and decreased serotonergic activity have been associated with delirium.
Serotonin agonists can induce psychosis, both elevated Trp availability and
increased cerebral serotonin have been associated with hepatic encephalopathy,
and excess serotonergic brain activity has been related to the development of the
serotonin syndrome of which delirium is a main symptom. On the other hand,
alcohol withdrawal delirium, delirium in levodopa-treated Parkinson patients, and
postoperative delirium have been related to reduce cerebral Trp availability from
plasma suggesting diminished serotonergic function. Rick factors for delirium
such as severe illness, surgery, and trauma can induce immune activation and a
physical stress response comprising increased activity of the limbichypothalamic-pituitary-adrenocortical axis, the occurrence of a low T3 syndrome,
and, possibly, changes in the permeability of the blood-brain barrier. There are
indications that these changes have their effect on plasma amino acid
concentrations, e.g., Trp, and multiple cerebral neurotransmitters, including
serotonin. This stress response may be different depending on the stage of
illness being acute or chronic. It will require further study to determine the
complex influence of the stress response and immune activation on plasma
amino acids, neurotransmitter function and the development of delirium,
especially in the more vulnerable older patients. [References: 52]
van der Mast, R. C., W. W. van den Broek, et al. (1999). "Incidence of and preoperative
predictors for delirium after cardiac surgery." Journal of Psychosomatic Research 46(5):
479-83.
Incidence of and preoperative predictors for postoperative delirium were studied
in 296 patients (age 26-83 years, mean age 63 years) undergoing elective
cardiac surgery. Delirium occurred in 40 (13.5%) patients. Predictors included old
age, low level of albumin, poor physical condition, use of nifedipine, and a high
ratio of the amino acids phenylalanine to the sum of isoleucine, leucine, valine,
tyrosine, and tryptophan. These findings suggest that preoperative physical
condition and amino acid disturbances may be related to delirium after cardiac
surgery in the elderly.
van der Mast, R. C., W. W. van den Broek, et al. (2000). "Is delirium after cardiac
surgery related to plasma amino acids and physical condition?" Journal of
Neuropsychiatry & Clinical Neurosciences 12(1): 57-63.
The authors studied interrelationships between plasma levels of amino acids,
physical condition (as apparent from cortisol, albumin, and thyroid hormone
concentrations), and postoperative delirium in 296 patients undergoing elective
cardiac surgery. Both plasma tryptophan (Trp) and ratio of Trp to the other large
neutral amino acids (oLNAA) were reduced in delirious patients compared with
control patients. The lower availability of Trp for the brain in delirious patients
may lead to decreased serotonergic function. Besides, the ratio of phenylalanine
(Phe) to the oLNAA was increased in delirium, which may result in a higher
synthesis of cerebral dopamine and norepinephrine. Delirious patients were also
in poorer physical condition than nondelirious patients, having decreased
albumin level and increased ratio of inactive reverse triiodothyronine (T3) to
active T3. Decreased Trp and increased Phe availability may give rise to an
imbalance in cerebral neurotransmitters and thus contribute to delirium.
Wong, C. P., P. K. Chiu, et al. (2005). "Zopiclone withdrawal: an unusual cause of
delirium in the elderly." Age & Ageing 34(5): 526-7.
We report a case of an elderly lady who was admitted for congestive heart
failure. She developed delirium during the course of her hospital stay. Multiple
investigations were performed but were unremarkable. Finally, a diagnosis of
abrupt zopiclone withdrawal causing delirium was made. Zopiclone was resumed
at a lower dose and delirium resolved completely.
Yennurajalingam, S., F. Braiteh, et al. "Pain and terminal delirium research in the
elderly." Clinics in Geriatric Medicine 21(1): 93-119.
This article highlights new developments in assessment and management of pain
and delirium. [References: 95]
Yokota, H., S. Ogawa, et al. (2003). "Regional cerebral blood flow in delirium patients."
Psychiatry & Clinical Neurosciences 57(3): 337-9.
The purpose of the present paper was to determine the possible mechanism of
delirium by using xenon-enhanced computed tomography to measure the
regional cerebral blood flow (rCBF) of the patients both during delirium and after
improvement from delirium. The rCBF measurements of the frontal, temporal and
occipital cortex during delirium ranged from 31.4 to 39.6 mL/100 g per min; the
rCBF of the thalamus and basal ganglia ranged from 47.5 to 52.4 mL/100 g per
min. After recovery from delirium the rCBF of both areas returned to normal. The
findings that reduced rCBF during delirium becomes normal once delirium
improves suggest that a possible cause of delirium may be the cerebral
hypoperfusion.