Which of the following may be present in those suffering from delirium select three?

Confusion and Delirium

Acute confusion and delirium are states characterized by impaired orientation, diminished attention, and aberrant perception. Alertness is usually well maintained, clarity and speed of thinking are diminished, and memories are poorly formed. Inattentiveness, poor concentration, and alerting to irrelevant stimuli are present. There is overlap between confusional and delirious states, and some investigators regard delirium as a subset of confusion. Delirium is characterized by disturbed perception with terrifying hallucinations, vivid dreams, fantasies, insomnia, and overactivity.

Acute confusional states have been reported after right MCA infarctions.370371 Mesulam and colleagues372 reported three cases of sudden onset of acute confusion accompanied by retropulsion, unsteady gait, incontinence, difficulty in using common objects, and lack of concern for the illness. Mental agitation evolved into a state of irritable sluggishness, inattention, and memory disorder. Mullalley and associates373 reported acute confusion in 13 patients with right parietal lobe lesions and in 4 with right temporal lobe lesions. Levine and Finkelstein374 added 8 patients with a behavioral disorder, characterized by hallucinations, delusions, agitation, and confusion, that was remotely related (by 1 month to 11 years) to right temporoparietal stroke or trauma. Dunne and coworkers375 found that 3% (19) of 661 patients with stroke presented with delirium, confusion, dementia, or psychosis. Nearly all had right hemisphere lesions. Elementary neurologic findings were either absent or subtle. In 41 patients with right MCA territory infarctions, Mori and Yamadori336 found acute confusion in 25 and acute delirium in 6.

Caplan and associates376 found that posterior right temporal lesions were more likely to produce acute confusion than posterior right parietal lesions. The propensity of temporal lesions to produce confusional states may be explained by the proximity of these lesions to the underlying limbic system. Confusional states that follow brain infarction may result from one of two processes: disrupted modulation of affective responses in the limbic system or disruption of right hemisphere networks subserving attention.

Confusion and Delirium

Acute confusion and delirium are states characterized by impaired orientation, diminished attention, and aberrant perception. Alertness is usually well-maintained, clarity and speed of thinking are diminished, and memories are poorly formed. Inattentiveness, poor concentration, and awareness of irrelevant stimuli are present. There is overlap between confusional and delirious states, and some investigators regard delirium as a subset of confusion. Delirium is characterized by disturbed perception with terrifying hallucinations, vivid dreams, fantasies, insomnia, and overactivity.

Acute confusional states have been reported after right MCA infarctions449-451 and may be accompanied by retropulsion, unsteady gait, incontinence, difficulty in using common objects, and lack of concern for the illness. Mental agitation can evolve into a state of irritable sluggishness, inattention, and memory disorder. The disorder has been found in conjunction with parietal as well as temporal lesions.410 Hallucinations, delusions, and agitation have also occurred.400,452,453

Caplan et al454 found that posterior right temporal lesions were more likely to produce acute confusion than posterior right parietal lesions. The propensity of temporal lesions to produce confusional states may be explained by the proximity of these lesions to the underlying limbic system. Confusional states that follow brain infarction may result from one of two processes: disrupted modulation of affective responses in the limbic system or disruption of right hemisphere networks subserving attention.

Confusion and Delirium

Acute confusion and delirium are characterized by impaired orientation, diminished attention, and aberrant perception. Alertness is usually well-maintained, clarity and speed of thinking are diminished, and memories are poorly formed. Inattentiveness, poor concentration, and awareness of irrelevant stimuli are present. There is overlap between confusional and delirious states, and some investigators regard delirium as a subset of confusion.

Acute confusional states have been reported after right MCA infarctions479–481 and may be accompanied by retropulsion, unsteady gait, incontinence, difficulty in using common objects, and lack of concern for the illness. The disorder has been found in conjunction with parietal as well as temporal lesions.440 Hallucinations, delusions, and agitation have also been described.430,482,483

Caplan et al.484 found that posterior right temporal lesions were more likely to produce acute confusion than posterior right parietal lesions. The propensity of temporal lesions to produce confusional states may be explained by the proximity of these lesions to the underlying limbic system. Recently, we described a case that showed an excellent recovery after intravenous thrombolysis for an acute right MCA stroke. A 73-year-old man presented left-sided weakness (NIHSS 19 points). CT angiography revealed right MCA occlusion. Continuous TCD monitoring revealed complete recanalization of right MCA at 14 minutes after treatment onset. This was accompanied by rapid and persistent clinical recovery (NIHSS score 1 point at 1 hour). However, despite brilliant clinical recovery, he displayed severe suicidal ideations on day 3. He had never suffered from depression or psychiatric illness in the past. Brain MRI showed an acute lacunar infarction in the putamen. TCD and CT perfusion were suggestive of right MCA hyperperfusion. Interestingly, electroencephalography (EEG) showed considerable slowing over the right hemisphere, even in the absence of any parenchymal damage. Head-up position, fluid restriction, and aggressive blood pressure control (120/80 mm Hg) resulted in rapid improvement in psychiatric features during the next 2 days. CT perfusion, TCD, and EEG abnormalities resolved completely within a few days. We hypothesize that neurovascular uncoupling due to acute stroke resulted in these transient findings.485 Post-stroke depression has been described in patients with small subcortical infarcts, suggesting that cerebral blood perfusion may play an important role in the development of post-stroke depression.486

Caring for Older Adults With Cognitive Impairments

Cognitive impairment in the aged person can take many forms, and it is important that you study them in more depth than is appropriate to address in this book. However, impairment in one particular aspect of an elderly person’s life, instrumental activities of daily living (IADLs), has been shown to be correlated with the presence of dementia and may be one of the early signs of cognitive changes.45,46 If there is impairment in one of the following four IADLs, a thorough mental status evaluation should be performed: (1) medication/health management, (2) money/financial management, (3) telephone management/communication device use, and (4) transportation management. We engage you in a general discussion about cognitive impairment and provide some general guidelines for respectful interaction with people with neuropathology that directly affects thought and speech processes.

Acute confusion or disorientation can be caused by a variety of factors, such as an infection, a fluid or electrolyte imbalance, or a cerebral vascular accident. It is important to determine the cause of confusion in an elderly patient and not just ascribe it to “being old.” The following case illustrates how critical it is to understand the genesis of a change in mental status in an older patient.

Case Study

Family members brought an 81-year-old man, Abraham Steinman, who was in an acutely agitated and confused state, to the emergency department. The family stated that Mr. Steinman had gradually become more confused over the past few weeks and became violently disturbed earlier in the evening. He was admitted to the adult psychiatric unit because he was physically violent to the staff in the emergency department. The distraught family said he had never had an emotional outburst in his life and could not understand his behavior. The next day a careful physical examination revealed that Mr. Steinman had bilateral pneumonia and some signs of kidney failure. His confusion and agitation had only been symptoms of his physical illness.

Reflections

What action might have prevented the admission to psychiatry?

Would the assessment and treatment have been the same if Mr. Steinman were 40 years old? If he were 20 years old?

How would you feel if this was your father?

What can the interprofessional care team treating Mr. Steinman learn from his case to improve the care of future patients?

For such patients, acute confusion can be continual and may be increasingly profound, although you can help diminish the patient’s suffering from disorientation at any given moment. Often, a useful approach is to not support the older person’s constantly confused ideas, unless correcting them causes him or her to become violent, further disoriented, or deeply agitated. If an old man thinks he is in a hotel, you should try to correct him using a gentle reassuring voice and manner.

If he confuses you with someone else, his mistake can be corrected by showing him your name badge and repeating your name. Chances are that he will be less frightened if the people around him are willing to help him clear up his mind, if only for a few minutes. It is a good general rule of respectful interaction to correct the person. However, you should also remember to listen with interest and politeness to the patient. Listening will help you determine the depth of the confusion, ascertain the wisdom of trying to correct it, and, in some cases, discern that the patient is making sense within a context not immediately evident.

Respect requires that the confused person should always be treated kindly. Spoken correction or redirection should never be condescending but rather should reflect the gentle authority that gives the patient a sense of security.

If the confusion is the result of a disease such as Alzheimer’s disease or another form of dementia, many of the same principles apply. Some additional strategies for communicating with patients with dementia are as follows: use broad opening statements or questions, try to establish commonalities, speak to them as equals, speak at a normal rate and without exaggerated intonation, eliminate distractions, repeat when necessary and according to whether the listener misunderstood versus forgot what was said, and try to recognize themes in what the patient is trying to share with you.47

Sometimes medication can help an agitated patient relax or in other ways be more comfortable, although with elderly patients it is best to be cautious with the use of medications. Goals must be adapted according to what patients can comprehend. Some patients may be unable to remember the simplest tasks from one testing or treatment period to the next and may never grasp the most elementary verbal instructions. Others, however, will be able to follow astonishingly complex procedures. It is your responsibility and opportunity in such situations to approach each person as an individual and to not take for granted that all confused utterances are signs of organic brain changes. In some cases, the confusion will increase no matter what is done. However, none of these complications should deter you from first attempting, in a kind way, to correct inaccuracies. With a great number of patients, this humane act is the key to respectful interaction.

Aphasia in Acute Confusional States and Dementias

Patients who develop acute delirium or confusion frequently utter meaningless or nonsensical phrases. In most cases this involves abnormal thought, or language content, rather than abnormal language, resembling a psychosis. In some cases, however, delirious patients produce fluent, paraphasic speech and even neologisms. Naming is frequently disturbed in acute confusional states. Comprehension is at least partially preserved, if the patient's attention and memory can be entrained to the task. Many delirious patients have abnormal writing. The diagnosis of delirium rests on a general confusional state, with impaired attention, reasoning, and often hallucinations and delusional thinking as well as agitation or drowsiness and autonomic signs such as tremor, sweating, tachycardia, hypertension, and fever. All of these ‘positive’ cognitive symptoms such as agitation, delusional thinking, and hallucinations, and also the autonomic signs, are much less prominent in dementing illnesses, except in advanced cases.

Patients with dementing diseases such as Alzheimer's disease frequently demonstrate abnormal language functions. The dementia of Alzheimer's disease usually begins with memory loss, and among the earliest symptoms is a loss of memory for names. Recollection of proper names and rapid generation of a series of names are very sensitive to aging and dementia. For example, patients with early dementia have marked difficulty with the ‘animal naming’ subtest of the BDAE, which requires the subject to name as many animals as possible in one minute. Articulation, repetition, and auditory comprehension tend to remain intact into later stages of dementia. At an early stage, an Alzheimer's disease patient often shows the profile of anomic aphasia. As the disease advances, reading and writing deteriorate, and auditory comprehension begins to decline. Repetition and articulatory fluency remain preserved, and the patient may then show the language profile of transcortical sensory aphasia. The content of expressive speech is also severely impoverished, devoid of abstract content. Ultimately, language expression becomes limited almost to statements of biological need. Some patients become mute in late stages, resembling global aphasia, while others repeat fluently.

Alzheimer's disease is a ‘diffuse’ degeneration of the cerebral cortex, but pathological studies indicate early involvement of the association cortex, particularly of the parietal and later the frontal lobes. Medial temporal structures such as the hippocampus, which are important to memory function, and medial forebrain structures such as the nucleus basalis, also show neuronal loss and senile plaques.

Other dementing diseases also produce language disorders. After Alzheimer's disease, the most common cause of dementia is multiinfarct or vascular dementia. The specific features depend on the size and location of the cerebral infarcts, but many patients manifest aphasia.

Pick's disease was described in the nineteenth century as a lobar atrophy involving predominantly the frontal and temporal cortices, with microscopic stains showing intraneuronal, silver-staining inclusions called ‘Pick bodies.’ Many cases with similar clinical and neuroradiological features lack Pick bodies, and the newer term for this family of focal neurodegenerative disorders is ‘FTD’ or ‘frontotemporal lobar degeneration.’ Some cases begin with ‘frontal’ syndromes of behavioral abnormality, others have isolated aphasia at onset. What was described in North America as ‘PPA’ is now thought to be a variant of the syndrome of FTD, described in Europe. Some cases of PPA have been followed for several years, with steadily worsening language function, usually with nonfluent, or Broca-like aphasia, but no significant memory loss or generalized dementia. Brain imaging studies show only a lobar atrophy. PET studies have consistently shown left frontal and/or temporal hypometabolism, with more advanced cases showing more widespread metabolic changes. The pathology is usually of lobar atrophy, without the typical changes of Alzheimer's disease, but with neuronal loss and glial scarring. A variant of the syndrome is ‘semantic dementia,’ in which patients speak fluently but lose their ability to name or even to comprehend the meaning of names given to them. This syndrome can be seen in either FTD or Alzheimer's disease. A great deal of research has been published recently on this family of conditions. Two different gene mutations have been found in familial cases of FTD and PPA, both entirely separate from the genes associated with Alzheimer's disease. Another disease that can present with progressive aphasia is corticobasal degeneration, a variant of Parkinson's disease also associated with mutations in the tau protein, one of the two gene mutations associated with FTD.

Creutzfeldt–Jakob disease is a more rapidly progressive dementia, often with myoclonus and seizures, and often a fatal course within several months. Numerous variants of the syndrome have been described. Aphasia has been documented as a presenting symptom of Creutzfeldt–Jakob disease, but the development of a rapidly progressive dementia with myoclonus and seizures usually makes the diagnosis clear.

Psychosis and Acute Confusional State

Patients with SLE can develop acute confusion or delirium. These patients may have an acute organic psychosis or acute cognitive deficit, with or without clouding of consciousness. The differential diagnosis includes metabolic derangements, hypertensive encephalopathy, medication toxicity, focal brain lesions, meningoencephalitis, seizures, and opportunistic infections. More than one mechanism often contributes for a single individual; therefore, these patients usually need a thorough clinical and laboratory evaluation as well as brain MRI, electroencephalography, and CSF examination.

In a small percentage of patients with SLE, episodes of acute psychosis develop. The psychosis can arise de novo or be provoked by initiation of or increase in corticosteroid therapy. Patients with hypoalbuminemia seem to be at increased risk for steroid-induced psychosis.16 When the psychosis is not attributable to steroids, high-dose steroids are often therapeutic. Reports of an association between autoantibodies to ribosomal P and psychosis have not been consistently confirmed.

Neurological manifestations

Encephalopathy, including change in level of consciousness, acute confusion, or bizarre and combative behavior, is the most common neurological complication. Encephalopathy occurs in 2–5% of patients and typically develops 1–3 weeks after illness onset. Seizures are common. Progression of symptoms from headache to lethargy and coma can be rapid (McGrath and Wallis, 1998; Massei et al., 2005). Potential clinical manifestations of CSD include aphasia, hearing loss, cranial neuropathy, hemiplegia, ataxia, transverse myelitis, acute disseminated encephalomyelitis (ADEM), cerebral arteritis, and PNS involvement including chronic inflammatory demyelinating polyneuropathy (Carithers and Margileth, 1991; Marra, 1995). Neuroretinitis can also develop presenting either unilaterally or, less commonly, with bilateral vision loss. Findings include central scotoma, optic disk swelling, and macular star formation.

Cerebrospinal fluid (CSF) analysis serves to exclude other conditions. The CSF profile is generally normal but can show a mild lymphocytic pleocytosis; routine culture is negative. Neuroimaging is usually normal but can show findings typically associated with ADEM or status epilepticus (Hahn et al., 1994; Ogura et al., 2004). During the acute stage of encephalopathy, electroencephalography (EEG) shows diffuse nonspecific slowing. Neurological complications are generally transient and most patients recover well; although recovery may take months in some cases.

Delirium

In the immediate postoperative period after DBS lead implantation, acute confusion and psychosis are relatively common, documented in 8.6% (1.6%–25.1%) of cases and is likely underreported in most clinical series (Table 24.1). Delirium may be more common after STN than GPi lead implantation.35 In patients with Parkinson’s disease, these acute changes are exacerbated by preexisting cognitive deficits and perioperative withdrawal of medications. Management consists of identifying and treating reversible hemodynamic, metabolic, and infectious etiologies; judicious use of opiates, benzodiazepines, anticholinergics, and other deliriogenic medications; and nonpharmacologic interventions including encouraging normal sleep–wake cycles and minimizing overnight awakenings.38 Dopaminergic and anticholinergic Parkinson’s medications can exacerbate delirium, as can withdrawal from these medications, and inpatient adjustment should involve consultation with a neurologist familiar with their use. Judicious use of antipsychotics may also be helpful, and in Parkinson’s disease the limited evidence generally favors quetiapine because it does not substantially worsen motor symptoms.39

Introduction

Dementia is a generalized loss of functions that results from cerebral disease. Dementia occurs in absence of acute confusion (i.e., the deficits do not occur exclusively during the course of a delirium). According to the American Psychiatric Association's Diagnostic and statistical manual of mental disorders (DSM-IV), a dementia syndrome is characterized by multiple deficits in cognition, including memory impairment, which are the direct consequence of physiological changes. The DSM-IV criteria require that these deficits must be of a sufficient magnitude to impair social or occupational function. Historically, diagnostic classifications for dementia have included subtypes based on characteristics such as typical symptoms presentation, the progression and course of the disease, and psychiatric and behavioral features, as well as presumed causes (e.g., a general medical condition, persisting effects of a substance, multiple etiologies). The concept of dementia has evolved over the past hundred years. It has long been associated with a progressive decline of cognitive functions and with an irreversible course. Nowadays, definitions of dementia are descriptive and rely on typical symptoms presentation, and thus do not necessarily imply a progressive degeneration. However, the primary progressive dementias are most common and often present with language and communication disorders.

As the population in Western countries ages, the prevalence of progressive dementias resulting from brain diseases increases. Recent epidemiologic studies have suggested that the prevalence of dementia in industrialized countries is approximately 1.5% at age 65 years, rising to approximately 25% by age 80 years (Lobo et al., 2000). For example, according to the Canadian Study of Health and Aging (1994), more than 364 000 Canadians over 65 suffer from dementia. Among these individuals, 65% presented with dementia of the Alzheimer's type (DAT) whereas the remaining suffer from vascular dementia (VaD) and other forms of dementia. Moreover, it is predicted that over three-quarters of a million Canadians will have Alzheimer's disease and related dementias by the year 2031. Thus, progressive dementia is becoming an increasingly important public health concern across the world.

Nervous System

A 70-year-old man taking metformin 500 mg twice daily for approximately 1 year experienced multiple episodes of recurrent acute confusion and drowsiness. Except for elevated creatinine levels, other labs, vitals, general and neurological examinations were unremarkable. During these episodes, metformin was routinely discontinued, while serum creatinine levels were actively lowered. Recovery always occurred within 2 days of metformin discontinuation. However, metformin was restarted each time he left the hospital, which resulted in a total of three of these episodes in a 6-month period. After the third episode, he was diagnosed with possible metformin-induced encephalopathy without lactic acidosis. Metformin was permanently discontinued, and he had not experienced further symptoms of encephalopathy. Metformin has been associated with iatrogenic encephalopathy secondary to hypoglycemia, acute liver failure and lactic acidosis, especially in renal impairment. The authors point out that the lack of encephalopathy following metformin discontinuation, despite recurrent episodes of elevated plasma creatinine, dispute the possibility that renal failure was the direct cause of the encephalopathy [41A].

The case presentations of MALA included a 70-year-old male with Stage 3 CKD (defined as GFR 30–60 mL/min per 1.73 m2 per the Renal Association in the United Kingdom), acute kidney injury and HF who presented with chest pain and progressive shortness of breath. He was being treated with 500 mg metformin twice daily for T2D. His admission labs showed acute kidney injury: serum creatinine, 2.2 mg/dL; lactic acid, 11.1 mmol/L; arterial pH, 7.03; serum bicarbonate, 3.8 mmol/L; anion gap, 26 mEq/L; blood glucose, 206 mg/dL; serum ketones, negative. His metformin level was 25 μg/mL (~ 10 times elevated). Immediate hemodialysis promptly resolved all metabolic parameters and returned metformin to 1.5 μg/mL (within therapeutic range of 1–2 μg/mL).

Next, a 56-year-old male with T2D, cirrhosis and acute kidney disease presented after a syncopal spell. Further examination revealed jaundice, ascites and pretibial pitting edema. The day before, a liver biopsy was performed in addition to paracentesis and removal of 4 L of ascitic fluid. His admission labs showed acute kidney injury, with a serum creatinine of 2.1 mg/dL (1.1 mg/dL baseline), bicarbonate of 18 mEq/L and anion gap of 12 mEq. Diuretics and lisinopril were held but metformin 500 mg twice daily was continued. On day 3, he developed altered mental status and respiratory failure. Labs were drawn to show worsening renal failure: serum creatinine, 3.2; lactic acid, 10.6 mmol/L; arterial pH, 7.0; PCO2, 21 mm Hg; serum bicarbonate, 4 mmol/L; anion gap, 47 mEq/L; aspartate aminotransferase, 3598 U/L; alanine aminotransferase, 898 U/L; INR, 7.0. His metformin level was 31 μg/mL. The patient underwent emergency hemodialysis, which resolved the high anion gap, metabolic acidosis and returned his metformin level to 5.4 μg/mL.

The last case of MALA was an intentional metformin overdose. The 60-year-old T2D male was a type 2 diabetic being treated with metformin and insulin (regular and neutral protamine Hagedorn). He reported ingestion of 5000 mg of metformin in addition to alcohol consumption. He was in mild distress with stable vitals upon admission. Treatment consisted of activated charcoal and intravenous hydration. His labs were as follows: serum creatinine, 0.8 mg/dL; lactic acid, 7.4 mmol/L; arterial pH, 7.35; anion gap, 22 mEq/L. He was admitted to the hospital for hemodialysis; however, the metabolic acidosis and his clinical status improved during the next 24 hours [42A].