Neuropsychiatry and Dementia - Neurological Differential Diagnosis

Approach to neurobehavioral evaluation 174

Neuropsychiatric interview 174

Clinical correlates of mental status impairment 175

Dementia evaluation 177

Neuropsychiatry and behavioral neurology 178

Clinical signs and symptoms 178

Disorders of perception 178

Memory disturbances 178

Transient global amnesia vs. psychogenic amnesia 179

Visual hallucinations 180

Auditory hallucinations 181

Pharmacologic agents and toxins associated with hallucinations 182 Neurological disorders and associated behavioral disorders 183 Neurological conditions that have depression as a prominent feature 183

Neurological causes of mania 184

Neurological conditions associated with psychosis 185

Neurological causes of episodic dyscontrol or violence 186 Common neurological disorders and associated behavioral disorders 187

Substance abuse and neurological symptoms 188

Neuro-ophthalmologic features of common neuropsychiatric disorders 189 Serotonin syndrome vs. neuroleptic malignant syndrome 190

Regional correlates of neuropsychiatric symptoms 191

Psychotic symptoms associated with focal brain abnormalities 192 Neuropsychological deﬁ cits associated with lateralized hemispheric damage 193

Dementia and delirium 193

DDx of dementia 193

Differentiating dementia and delirium 194

Criteria for diagnosis of probable Alzheimer disease 195

Infectious causes of dementia 196

Rapidly progressive dementia 197 Creutzfeldt-Jakob disease: sporadic form versus variant 198

DDx of delirium or acute confusional state 199

Hydrocephalus and dementia 201

Speciﬁ c behavioral syndromes like aphasia, apraxia, etc. are covered in Chapter 2.

Approach to neurobehavioral evaluation Neuropsychiatric interview

Components of the neuropsychiatric interview and mental status examination 1 Interview:

◆ Appearance: well-groomed, disheveled

◆ Motor behavior: restless, akathisia, tremor, waxy ﬂ exibility

◆ Mood and affect: depressed, energized, cheerful, ﬂ at, blunted

◆ Verbal output: sparse, verbose, pressured

◆ Thought: circumstantial, ﬂ ight of ideas, perseveration

◆ Perception: misperceptions, illusions, hallucinations 2 Mental status examination:

◆ Attention and concentration: digit span forward and backward

◆ Language: ﬂ uency, comprehension, reading, writing, repetition

◆ Memory: registration, immediate and delayed recall

◆ Construction: drawing objects

◆ Calculation skills: mathematics, word problems

◆ Abstraction: similarities, proverbs

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Assessing the patient’s general appearance is the ﬁ rst observation made in the neuropsychiatric examination. For example: a disheveled appearance reﬂ ecting a lack of self-care occurs in frontal lobe syndromes; a unilateral dressing disturbance occurs in hemispatial neglect.

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Disturbances of motor function are among the most revealing aspects of the neuropsychiatric examination. For example: 1) retarded depression is characterized by psychomotor slowing, long latencies of reply, and paucity of verbal output; 2) catatonic behavior with stereotypy and waxy ﬂ exibility can be seen in affective disorders.

◆ Insight and judgment: problem solving, hypothetical examples (what would you do if …?)

◆ Praxis: ability to perform complex motor tasks (brush teeth, comb hair, etc.)

◆ Frontal lobe system tasks: executive planning, Luria hand sequence

◆ Right-left orientation

◆ Finger identiﬁ cation

Clinical correlates of mental status impairment

Test Abnormal performance

Clinical correlates of poor performance

Attention

Digit span < 5 digits Delirium

Advanced dementia Conduction aphasia

‘A’ test: series of letters, patient identiﬁ es all ‘A’s

Errors of omission Delirium

Frontal lobe dysfunction Serial subtraction Erroneous subtraction Delirium

Dementia Acalculia, amnesia

Digit span backwards < 4 digits Delirium Dementia

Frontal lobe syndrome Reversed spelling Slowing or failure Delirium

Dementia

Frontal lobe syndrome

Continued

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When testing mental status, remember there is a hierarchy of performance.

If the patient is unable to perform a basic task, then detailed testing of higher functions will not necessarily refl ect a specifi c localization-related defi cit.

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Basic tasks include tasks of attention, language, and recognition. If a patient is unable to attend (such as in an acute confusional state/delirium), then deﬁ cits in memory or calculations, etc. should be interpreted with caution.

Similarly, if a patient demonstrates a receptive aphasia, then failure to complete other tasks may not reﬂ ect additional deﬁ cits, but merely the inability to follow the examiner’s commands.

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It is generally sensible to test basic functions ﬁ rst, and then modify the level of detail of the remainder of the mental status exam based on performance of these basic functions.

Test Abnormal performance

Clinical correlates of poor performance

Memory

Word list learning Recall & recognition impaired Amnesia with left hemispheric lesions Cortical dementia

Word list learning Recall impaired, recognition intact

Frontal subcortical system dysfunction

Figure learning Recall & recognition impaired Amnesia with right hemispheric lesions Figure learning Recall impaired, recognition

intact

Frontal subcortical system dysfunction

Remote recall Variable: temporal gradient present

Amnesia

Remote recall Impaired: no temporal gradient Dementia

Language

Spontaneous speech Fluent aphasia Posterior left hemispheric lesion Spontaneous speech Non-ﬂ uent aphasia Anterior left hemispheric lesion Comprehension Impaired Posterior left hemispheric lesion

Repetition Impaired Left perisylvian lesion

Naming Impaired Left or right hemispheric lesion

Delirium Dementia

Writing Agraphia Left parietal lobe lesion

Reading Alexia without agraphia Left medial occipital lesion (and splenium?)

Alexia with agraphia Left parietal lobe lesion

Word list generation Reduced Anomia

Left frontal lobe lesion Psychomotor retardation

Miscellaneous

Calculation Acalculia Left inferior parietal lesion

Abstraction Concrete Dementia

Frontal lobe syndrome

Judgment Impaired Dementia

Frontal lobe syndrome Motor programming Perseveration Lateral convexity of frontal lobes

Praxis Apraxia Left hemispheric lesion

Corpus callosum

Dementia evaluation

1 Core laboratory tests

◆ Complete blood count

◆ Serum electrolytes, calcium, glucose, blood urea nitrogen, creatinine, liver function tests

◆ Thyroid-stimulating hormone

◆ Serum vitamin B₁₂

◆ Structural imaging study 2 Ancillary investigations

◆ Syphilis serology (RPR)

◆ Sedimentation rate (ESR)

◆ HIV testing

◆ Chest X-ray

◆ Urinalysis with 24-hour urine collection for heavy metals and toxicology screen

◆ Neuropsychological testing

◆ Apo-E genotyping, Aβ42/tau CSF analysis

◆ Electroencephalography

◆ Single-photon emission computed tomography (SPECT)

◆ Positron emission tomography (PET)

Note: apolipoprotein E genotyping is not useful in isolation from the clinical cri-teria of Alzheimer disease, but may increase the sensitivity of the diagnosis when patients do not have the _Є-4 allele. Another biomarker for diagnosis of Alzheimer disease is the combined assessment of CSF amyloid β(1–42) protein (Aβ42) and tau concentrations, which has a sensitivity of 85% and speciﬁ city of 87%.

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There is no single battery of laboratory tests that would adequately screen for all causes of dementia. In addition, many syndromes lack pathognomonic laboratory features that would allow such identiﬁ cation.

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Correct diagnosis of a dementing illness depends critically on the integration of clinical history, neurological, and general physical

examinations, and mental status assessment as well as selected laboratory tests.

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Laboratory assessment of patients with suspected dementia is targeted to identify REVERSIBLE causes, with a core group of laboratory tests that should be performed on all demented patients for this purpose. Ancillary investigations are recommended when suspicion for a speciﬁ c diagnosis is high.

Neuropsychiatry and behavioral neurology Clinical signs and symptoms

Disorders of perception

1 Positive phenomena

◆ Hallucinations: formed or unformed distortions occurring without external stimulus

◆ Illusions: distortions or misinterpretations of existing stimuli

◆ Palinopsia: visual images that persist even when gaze direction changes 2 Negative phenomena

◆ Unilateral neglect

◆ Blindness

◆ Achromatopsia (central color blindness)

◆ Agnosia (inability to recognize)

◆ Visual object agnosia

◆ Prosopagnosia (agnosia for familiar faces)

◆ Environmental agnosia (agnosia for familiar places)

◆ Simultagnosia (inability to perceive multiple objects as a single entity at once)

◆ Color agnosia

Memory disturbances

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Abnormalities of perception may be classiﬁ ed according to modality (visual, auditory, touch, olfactory, and gustatory) and whether they represent positive or negative phenomena.

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Disorder of visual perception is the most common disorder of perception seen in clinical practice.

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For clinical purposes, memory disturbances can be divided into those that are short-lived (less than 24–48 hours) and those that are more prolonged.

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Alternatively, memory disturbances can be divided into stable and progressive.

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Amnesia refers to a speciﬁ c clinical condition in which there is an impairment in the ability to learn new information despite normal attention, preserved ability to recall remote information, and intact cognitive functions.

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Amnesia should be distinguished from other causes of memory disturbances associated with lapses of consciousness including seizures, alcoholic

blackouts, migraine, etc.

1 Transient episode of memory loss (< 48 hours) 1.1 Amnesia

■ Transient global amnesia (TGA) – (see below)

■ Psychogenic amnesia

■ Post-traumatic amnesia

1.2 Memory lapses associated with alterations of consciousness

■ Seizures

■ Alcoholic blackouts

■ Migraine

■ Toxic-metabolic confusional states

■ Benzodiazepine-induced amnesia 2 Prolonged period of memory loss (> 48 hours)

2.1 Amnestic syndromes

■ Head trauma

■ Wernicke-Korsakoff syndrome

■ Herpes simplex encephalitis

■ Hippocampal infarction

■ Basal forebrain lesions 2.2 Dissociative states

■ Fugues

■ Multiple personality disorders 2.3 Minimal cognitive impairment (MCI) 2.4 Dementias

■ Alzheimer disease

■ Subcortical dementias

Transient global amnesia vs. psychogenic amnesia

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Psychogenic amnesia is most likely to be confused with transient global amnesia (TGA), especially in patients presenting with acute onset.

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However, there are several characteristics that aid in the differentiation of psychogenic amnesia from TGA.

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The most important clue is that TGA almost never includes a loss of personal identity, whereas it is one of the hallmarks in psychogenic amnesia.

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Psychogenic amnesia should also be distinguished from episodic disturbances of consciousness, such as those associated with complex partial seizures.

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The exact cause of TGA is still unclear. However, recent cerebral blood ﬂ ow studies suggested diminished blood ﬂ ow in the posterior hemispheric and inferior temporal regions.

Transient global amnesia Psychogenic amnesia A distinct clinical syndrome consisting of an

acute period of amnesia lasting less than 24 hours

Hysterical conversion symptom in which patients suddenly forget their identity and life situations

Personal identity retained Personal identity lost

Unable to learn new information Ability to learn new information preserved Amnesia not selective Memory loss may be selective for speciﬁ c

information Temporal gradient present, with relative

preservation of remote memory beyond the period of retrograde amnesia

Temporal gradient absent

Depression and anxiety infrequent Depression and anxiety common Distressed by amnesia Indifferent to amnesia

Common in older patients (5th to 7th decades)

Common in younger patients (teens–3rd decades)

Visual hallucinations

1 Lilliputian hallucinations

◆ Vision of tiny humans and animal ﬁ gures, named after the diminutive inhabit-ants of the Isle of Lilliput.

◆ They are distinctive but appear to have little etiologic signiﬁ cance. They have been described in toxic/metabolic disorders, epilepsy, ocular diseases, affective disturbances, and schizophrenia.

2 Brobdingnagian hallucinations

◆ Hallucinations of giants.

◆ Have been reported in a small number of acute confusional state cases.

3 Autoscopy (heutoscopy)

◆ Striking hallucinations in which one sees one’s own image.

◆ May suggest underlying organic brain disorders including epilepsy, tumor, trauma, subarachnoid hemorrhage, migraine, and infections. Also occurs with schizophrenia and depression.

4 ‘Psychedelic’ hallucinations

◆ Characterized by geometric forms, spirals, funnels, and chessboards that are most characteristic of the hallucinogenic drugs. However, can also occur with

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There are no etiology-speciﬁ c or pathognomonic types of hallucinations, though features of visual hallucinations may facilitate identiﬁ cation of the clinical disorders from which they originate.

sensory deprivation, and have been described in CNS disorders such as during recovery from acute viral encephalitis and with acute occipital lobe insults.

5 Palinopsia

◆ A unique form of visual hallucination that involves the persistence or recurrence of visual images after the exciting stimulus has been removed. The images re-main when the patient changes direction of gaze and may spontaneously recur.

◆ Palinopsia can occur with lesions in either hemisphere, but is most common with acute damage to the posterior aspect of the non-dominant hemisphere.

◆ It has also been reported as a possible side-effect of trazodone and LSD intoxi-cation.

Auditory hallucinations

Etiologies of auditory hallucinations:

1 Psychiatric disorders: the most common cause of auditory hallucinations

◆ Schizophrenia, occurs in 60–90% of patients

◆ Depression

◆ Mania

◆ Post-traumatic stress disorder 2 Toxic metabolic disorders

◆ Chronic alcoholic hallucinosis

◆ Occurring as part of delirium?

3 Peripheral lesions

◆ Deafness can be caused by the disease of middle ear, inner ear, and auditory nerve. This may produce both unformed and formed hallucinations.

4 CNS disorders

◆ Temporal lobe epilepsy

◆ Pontine lesions

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Auditory hallucinations, unlike visual hallucinations, are more characteristic of idiopathic psychiatric disorders than of neurological or toxic metabolic disorders.

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An important exception to this observation is the common occurrence of auditory hallucinations in schizophrenia-like psychosis that may be associated with a variety of medical and neurological disorders.

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Unformed auditory hallucinations are called tinnitus, whereas formed hallucinations consist of melodies and occasionally voices.

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Deafness and auditory hallucinations appear to predispose to the development of paranoia in the elderly.

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Musical hallucination is a unique type of auditory hallucination and is most common with deafness. It can also be caused by central nervous processes, such as epilepsy, and can occur with depression and schizophrenia.

Pharmacologic agents and toxins associated with hallucinations

1 Hallucinogens

◆ Lysergic acid diethylamide (LSD)

◆ MDMA (ecstasy)

◆ Ketamine

◆ Abused inhalants, including ether, gasoline, glue, and nitrous oxide.

2 Antiparkinsonian medications: all anti-Parkinsonian medications have been reported to cause hallucinations.

◆ Anticholinergic drugs

◆ Levodopa

◆ Dopamine agonists, including pramipexole, ropinirole, pergolide, and bro-mocriptine

◆ Amantadine

◆ Selegiline

◆ Catechol-O-methyltransferase inhibitors (COMTI), including entacapone and tolcapone

3 Drugs associated with withdrawal syndromes

◆ Barbiturates

◆ Benzodiazepines

◆ Chloral hydrate

◆ Opiates

◆ Ethyl alcohol 4 Miscellaneous

◆ Cimetidine

◆ Digoxin

◆ Lithium

◆ Antidepressants, e.g. imipramine

◆ Corticosteroids

◆ Propanolol

◆ Disulﬁ ram

◆ Thyroxin

◆ Amphetamines

◆ Sympathomimetics

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Among all medications, hallucinations commonly occur with four major groups: hallucinogens, anti-Parkinsonian medications, drugs associated with withdrawal syndromes, and a miscellaneous group.

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Any medications, when taken in excess, may produce an acute confusional state with concomitant hallucinations.

Neurological disorders and associated behavioral disorders

Neurological conditions that have depression as a prominent feature 1 Multiple sclerosis

◆ Up to 80% of patients with multiple sclerosis have depressive symptoms.

◆ In addition, treatment with interferon ß-1b has been associated with new-onset depression.

2 Extrapyramidal diseases

2.1 Idiopathic Parkinson disease (PD) and other Parkinsonian syndromes

■ Approximately 50% of PD patients will experience depressive episodes during the course of illness.

■ Risk factors include female gender with a past history of depression.

■ Depression in PD is associated with more impaired cognitive function, the presence of psychotic features, and greater disability.

■ Proﬁ les of depression in PD include dysphoria, pessimism, and promi-nent somatic symptoms with less guilt and self-blame.

■ In other Parkinsonian syndromes, depression is observed in:

■ 20% of patients with progressive supranuclear palsy

■ 75% of patients with corticobasal ganglionic degeneration

■ 50% of patients with diffuse Lewy body disease 2.2 Huntington disease (HD)

■ Approximately 40% of patients with HD have mood disorders.

■ The mood change in HD is not just a reaction to the illness, but reﬂ ects the underlying neuropsychiatric manifestation of the disease.

■ HD is also associated with a marked increased in suicide rate, up to 8 times greater among patients age 50–69 years old compared to a control group.

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Depression is a broad term that encompasses changes in mood as well as a complex clinical syndrome. It includes sadness, anhedonia, and impaired ability to experience pleasure.

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The interaction between depression and neurological diseases is complex.

When depression precedes the onset of neurological disease, it is usually unclear whether the depression is the ﬁ rst manifestation or coincidentally preceded the onset of the brain syndrome.

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Depression itself can cause cognitive impairment, resulting in a dementia syndrome of depression or pseudodementia.

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In general, depression is under-recognized in neurological conditions and even when recognized, patients tend to be under-treated for depression.

3 Primary degenerative dementias

◆ Alzheimer disease (AlzD) and frontotemporal dementia

■ Patients with cortical dementia tend to exhibit less severe depression than those with subcortical disorders.

■ Approximately 40% of AlzD patients have depression.

4 Cerebrovascular disease

◆ Up to 33% of stroke patients will experience depression.

◆ Correlation between stroke location and risk of depression has been contro-versial.

◆ Vascular depression is a rather new term, suggesting that the late-onset de-pression is related to silent cerebral infarction and subcortical white matter lesions.

5 Epilepsy

◆ Depression in epilepsy patients may occur as part of a prodromal emotional change, part of an aura, part of an ictal manifestation, following seizures as part of the post-ictal state and lastly, may be an interictal manifestation.

◆ Interictal depression is the most common type of psychopathology observed in epilepsy patients and is associated with complex partial seizures with left-sided foci.

◆ Situational depression may also occur and can result from anticipation of sei-zures, reduced socialization, and decreased work productivity.

◆ Interactions between anticonvulsants and antidepressants should always be considered in each patient. Monoamine oxidase inhibitors are least likely to exacerbate seizures.

6 Others

◆ Traumatic brain injury

◆ CNS infections

◆ Cerebral neoplasms

Neurological causes of mania

1 Right hemispheric lesions

◆ In epilepsy, hypomania is usually seen peri-ictally, in the setting of clusters of right-sided temporal seizures.

◆ Other causes have been reported, such as stroke, and traumatic brain injury.

2 Parkinson disease with dopaminergic therapy

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Mania is usually primary but may be secondary to other medical conditions.

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The most common associations are with lesions in the right hemisphere involving the orbitofrontal cortex, caudate nuclei, thalamus, and basotemporal area.

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