Key Points for Issue

Psychiatry and Behavioral Neurology p. June 2018, Vol.24, No.3 doi: 10.1212/01.CON.0000534997.62480.df
Key Points for Issue
BROWSE ARTICLES
KEY POINTS

Anxiety disorders are the most common class of emotional disorders and an important cause of disability worldwide.

The prefrontal cortex, insula, and amygdala are key structures in the pathophysiology of anxiety.

Reduction in the activation of the prefrontal cortex–amygdala circuit to aversive stimuli may be a common neurobiological mechanism underlying effective treatments for anxiety.

First-degree relatives of those with anxiety disorders have an increased risk of developing any anxiety disorder or major depressive disorder.

Anxiety disorders are polygenic, with estimated genetic heritability estimates of between 30% and 50%.

Most anxiety disorders have their onset in childhood, and cases of atypical “late-onset” anxiety should be considered as due to medical, substance, or mood disorder factors until proven otherwise.

Environmental factors involving danger or threat, such as abuse or parental loss, increase the risk of developing an anxiety disorder later in life.

Females are twice as likely to manifest anxiety disorders compared to males.

Panic attacks typically present as the perception of frightening physical symptoms, such as racing heart, shortness of breath, and sweating, in the presence of normal vital signs and medical investigations.

A pattern of recurrent and uncued panic attacks is necessary for a diagnosis of panic disorder.

In the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), the presence of panic disorder is no longer required to make a diagnosis of agoraphobia.

Generalized anxiety disorder is associated with high rates of comorbid conditions, such as physical health issues, substance abuse, and mood disorders.

Social anxiety disorder is a chronic condition associated with fear of negative appraisal by others, excessive or unrealistic fear of social or performance situations, and intolerance of the possibility of embarrassment or scrutiny by others in social situations.

Phobias in childhood may be transient, but those that persist into adulthood will typically remain chronic.

Separation anxiety disorder, which is characterized by excessive fear or anxiety regarding separation from attachment figures, has pathophysiologic links to panic disorder and is a new addition to the group of anxiety disorders in DSM-5.

The most important step in the treatment of anxiety is the establishment of the diagnosis, which includes an exploration of the nature of the symptoms and an assessment of comorbid medical and psychiatric factors such as mood disorders, suicidality, and substance use.

Anxiety disorders are chronic but treatable conditions.

Selection of the appropriate treatment modality for anxiety disorders may, in part, be guided by symptom severity and by patient-rated questionnaires, such as the Generalized Anxiety Disorder 7-Item Scale.

Education about the nature of anxiety disorders, avoidance of known exacerbating factors, the promotion of healthy coping strategies, and emotional support should be provided to all patients.

A stepped-care approach for those with moderate or severe anxiety has been recommended.

The routine coadministration of psychotherapy and medications has not been shown to be superior to either approach alone.

Robust data exist to support cognitive-behavioral therapy in the treatment of anxiety disorders, whether administered directly by a therapist or via the Internet.

US Food and Drug Administration–approved medications for the treatment of anxiety disorders are from four pharmacologic classes: selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, azapirones, and benzodiazepines.

To minimize the risk of premature discontinuation of medication, start at a low dose and slowly increase the dose every 2 to 4 weeks up to the therapeutic range.

The azapirone medication buspirone has antianxiety effects limited to reduction of worry. As such, it has limited effects for other indications beyond generalized anxiety disorder, although it may be a helpful option when the use of a benzodiazepine is contraindicated.

The beta-blocker propranolol may be effective for peripheral manifestations of anxiety (eg, tremor) in those with the performance subtype of social anxiety disorder.

The risk of suicide is increased in those with anxiety disorders, especially in cases of a comorbid mood disorder or substance abuse.

Benzodiazepines should be avoided in those with alcohol or substance abuse and should be used with caution in the elderly.

A lack of response to an adequate course of either psychotherapy or medication should prompt a reexamination of the diagnosis, confirmation of treatment adherence, and ruling out of latent comorbid factors.

Options for those with a lack of response to treatment for an anxiety disorder may include (1) switching from medication to psychotherapy or vice versa, (2) combining medication and psychotherapy, (3) switching between antidepressant medication classes, or (4) adding a medication to an antidepressant or psychotherapy to augment its effects.

Article Level Metrics

Behavioral Neurology and Psychiatry

Article 1: Bedside Approach to the Mental Status Assessment

David F. Tang-Wai, MDCM, FRCPC; Morris Freedman, MD, FRCPC, FAAN. Continuum (Minneap Minn). June 2018; 24 (3 Behavioral Neurology and Psychiatry):672–703.

ABSTRACT

PURPOSE OF REVIEW

This article presents a clinically useful approach to obtaining the history and performing the mental status examination of patients with cognitive, language, or behavioral problems.

RECENT FINDINGS

Laboratory and imaging biomarkers are being developed for accurate diagnosis of neurobehavioral disorders, yet few are currently available for clinical use. Moreover, not all centers have access to these potential tools. Practicing clinicians are therefore left primarily with their skills of history taking and examination. Although geared for research, diagnostic criteria have been refined over the past several years and can nevertheless aid the clinician with the diagnosis of disorders such as mild cognitive impairment, Alzheimer disease, frontotemporal dementia, dementia with Lewy bodies, the primary progressive aphasias, corticobasal syndrome, vascular cognitive impairment, and posterior cortical atrophy. Regularly revised criteria reflect ongoing knowledge gained from in-depth studies of these disorders.

SUMMARY

The focused history and mental status examination remain essential tools for the evaluation and diagnosis of neurologic disorders affecting cognition, language, and behavior.

KEY POINTS

  • The mental status examination tests the integrity of cognitive domains (executive function, attention, memory, visuospatial function, language) in a clinical setting and is, therefore, a formal part of the neurologic examination.
  • Longitudinal assessments, combined with the mental status examination, provide additional information to determine if a change has occurred.
  • It is clinically useful to determine a patient’s cognitive profile (a patient’s relative strengths and weaknesses across the cognitive domains tested) as it will help the clinician, in conjunction with the history, elemental neurologic examination, and neuroimaging, to determine the underlying cause of cognitive impairment.
  • It is important to obtain the history from a collateral informant in addition to the patient to clarify the presenting symptom, to determine the chronologic progression of the signs and symptoms, and to determine the course of the progression (gradual, fluctuating, or stepwise).
  • The collateral historian need not always be a family member but can be anyone who has observed cognitive difficulties, can comment on them by providing specific examples, and can report whether the observed cognitive difficulties have caused any impairment with the patient’s usual ability to perform instrumental activities of daily living.
  • The ideal documentation should include the onset of the condition (insidious or acute), presenting symptom, course of the condition (gradually progressive, stepwise, fluctuating, or improving), and duration.
  • It is important not to interpret each “memory” complaint as an impairment in anterograde (short-term) memory as it is common for an informant to describe any cognitive deficit as a memory deficit. Instead, ask for examples of the presenting symptom to determine accurately what the informant means by “memory deficits.”
  • The history must include a description of the patient’s cognitive, behavioral, physical, and functional decline.
  • Changes in behavior can accompany any patient with cognitive impairment and can occur before the onset of cognitive symptoms, progress with the cognitive symptoms as a major feature of the dementia, or be part of a recognized symptom complex, such as in limbic encephalitis.
  • It is best to obtain the chronologic sequence of the changes in a patient’s cognitive, behavioral, physical, and functional decline. Although many neurodegenerative dementias have overlapping impairments, the chronologic sequence of events may help determine the type of dementia.
  • Additional details must be elicited to determine the true cause of the disability when the patient either has difficulties with or is incapable of performing a specific function.
  • Be mindful of multiple medications used to treat a condition (eg, hypertension); although it may be a medically resistant condition, it could also indicate noncompliance because of forgetfulness that the prescribing physician is unaware of.
  • The cognitive assessment should not only determine the domains that are impaired but also determine the domains on which the patient may perform normally.
  • A profile of impaired memory with preservation of function in other domains, together with intact activities of daily living, suggests amnestic mild cognitive impairment.
  • Clinicians should use the information obtained in the history to guide them in selecting and interpreting a cognitive assessment as no single cognitive test can accurately diagnose all conditions; each test has some limitations in its sensitivity to detect abnormal function as well as limitations in specificity.
  • When the cognitive test is insufficient because either the patient’s symptoms are too mild to be detected by the test or the patient’s symptoms are not well assessed by the test, a different test should be chosen or the test should be supplemented with additional bedside tests that would further examine the cognitive issues.
  • Common cognitive profiles/patterns include amnestic, executive dysfunction, visuospatial impairment, and language dysfunction.
  • In the amnestic pattern, the major difficulty is on tests of delayed recall and recognition.
  • In the executive dysfunction or frontal-subcortical pattern, major difficulties on tests include impairments on the Trail Making Test Part B (letter-number sequencing) and in digit span, letter cancellation, phonemic fluency (number of words beginning with a certain letter generated in 1 minute), similarities, or serial subtractions, with relative preservation in the other cognitive domains.
  • In the visuospatial impairment pattern, patients have difficulties on tasks that require drawing, whether copying a figure (eg, Benson complex figure, intersecting pentagons) or drawing an object (eg, free-drawn clock).
  • In patients with language dysfunction, depending on the severity and type of the language dysfunction, difficulties may be seen with naming in association with poor performance on sentence repetition, semantic knowledge, writing, comprehension, and reading and writing.
  • In most cases of dementia due to Alzheimer disease, the general neurologic examination is normal. In other causes of dementia, it is clinically useful to determine the presence of specific extraocular movement abnormalities, upper motor neuron signs, or parkinsonism.

Article 2: Clinical Assessment of Prefrontal Lobe Functions

Alexandre Henri-Bhargava, MDCM, MScCH, FRCPC; Donald T. Stuss, OC, O Ont, PhD, FRSC, FCAHS, CPsych, ABPP-CN; Morris Freedman, MD, FRCPC, FAAN. Continuum (Minneap Minn). June 2018; 24 (3 Behavioral Neurology and Psychiatry):704–726.

ABSTRACT

PURPOSE OF REVIEW

Whereas it was previously thought that there was a single overarching frontal lobe syndrome, it is now clear that several distinct cognitive and behavioral processes are mediated by the frontal lobes. This article reviews these processes and the underlying neuroanatomy and provides an approach to the assessment of prefrontal lobe functions at the bedside.

RECENT FINDINGS

Cognitive and behavioral frontal lobe functions are mediated by the prefrontal regions rather than the frontal lobes as a whole. At least five separate prefrontal functions have been defined: energization, task setting, monitoring, behavioral/emotional regulation, and metacognition. Energization is mediated by the superior medial prefrontal cortices bilaterally, task setting by the left lateral frontal cortex, monitoring by the right lateral prefrontal cortex, behavioral/emotional regulation by the orbitofrontal cortex, and metacognition by the frontal poles. Only task setting and monitoring are considered executive functions.

SUMMARY

Distinct cognitive and behavioral processes are mediated by different parts of the frontal lobe. Lesions in these areas result in characteristic clinical deficits that are discussed in this article. Key messages are that prefrontal regions mediate the higher cortical functions (as opposed to the frontal lobes in general) and that prefrontal functions are not equivalent to executive functions.

KEY POINTS

  • The terms frontal functions and prefrontal functions are often used synonymously to mean the higher-order cognitive and social-emotional functions associated with the frontal lobes. However, the more precise term is prefrontal functions.
  • Although the terms prefrontal functions and executive functions are sometimes used synonymously, executive functions comprise only a subset of prefrontal functions.
  • Five component processes have been identified as separate prefrontal lobe functions: energization, task setting, monitoring, behavioral/emotional regulation, and metacognition.
  • Energization is the process of initiating or sustaining any nonreflex response. This is mediated by the superior medial frontal regions bilaterally.
  • Task setting and monitoring are the two prefrontal lobe processes that fit the definition of executive functions.
  • Task setting refers to developing and implementing a plan for carrying out activities such as paying bills. This is mediated by the left lateral frontal region.
  • Monitoring is the process of checking that one remains on task over time, with adjustments in behavior as required for successful completion. This is mediated by the right lateral prefrontal region.
  • Behavioral and emotional regulation is mediated by the orbitofrontal cortex, while metacognitive processes are mediated by the frontal poles.
  • History from a collateral informant who knows the patient well is critical when assessing prefrontal function.
  • Phonemic word fluency (also known as lexical word fluency) can be a useful index of energization.
  • The lateral prefrontal lobes are important for working memory, the ability to consciously retain and manipulate information in the short term.
  • The digit span test is a simple test of working memory that is often used at the bedside.
  • Tests of abstract thinking are used to test executive function and tap into task-setting functions.
  • Clock drawing is a very popular bedside cognitive test that taps into prefrontal function.
  • Behavioral disinhibition, emotional dysregulation, and altered social cognition are seen in patients with orbitofrontal cortex lesions.
  • The frontal poles integrate information from other prefrontal regions and are involved in metacognitive functions such as theory of mind, (ie, being able to take the perspective of others and self-awareness).

Article 3: Memory Dysfunction

G. Peter Gliebus, MD. Continuum (Minneap Minn). June 2018; 24 (3 Behavioral Neurology and Psychiatry):727–744.

ABSTRACT

PURPOSE OF REVIEW

This article reviews the current understanding ofmemory system anatomy and physiology, as well as relevant evaluation methods and pathologic processes.

RECENT FINDINGS

Our understanding of memory formation advances each year. Successful episodic memory formation depends not only on intact medial temporal lobe structures but also on well-orchestrated interactions with other large-scale brain networks that support executive and semantic processing functions. Recent discoveries of cognitive control networks have helped in understanding the interaction between memory systems and executive systems. These interactions allow access to past experiences and enable comparisons between past experiences and external and internal information. The semantic memory system is less clearly defined anatomically. Anterior, lateral, and inferior temporal lobe regions appear to play a crucial role in the function of the semantic processing system. Different but tightly interconnected cortical regions, such as the prefrontal region, may play a controlling role in this system. The presentation of clinical disease affecting memory is the result of the selective vulnerability of the memory system. An understanding of current concepts of memory anatomy, physiology, and evaluation plays a central role in establishing an accurate diagnosis.

SUMMARY

Different memory systems rely on separate but overlapping distributed brain networks. Certain pathologic processes preferentially affectmemory systems. An understanding ofmemory formation stages will enable more accurate diagnosis.

KEY POINTS

  • Memory is classified into declarative and nondeclarative forms. Declarative memory is further classified into episodic and semantic. Nondeclarative memory is classified into procedural memory, priming, and classical conditioning.
  • Working memory is the brain’s ability to keep information active after it is no longer available in the environment.
  • Working memory function is supported by brain networks connecting frontal, parietal, and temporal lobes and has specialized parts for holding verbal, object, and spatial information.
  • The episodic memory formation process can be divided into encoding, storage, and retrieval stages.
  • Medial temporal lobe structures (entorhinal cortex and hippocampus) play a critical role in linking information represented in different cortical regions and its transfer from short-term to long-term storage.
  • Executive control networks are active along medial temporal lobe structures during memory encoding and retrieval. Semantic processing networks are also activated during information encoding.
  • An anatomically and functionally intact Papez circuit is important in information transfer from short-term to long-term storage.
  • The amygdaloid complex plays a role in the emotional enhancement of memories, increasing the probability that information will be encoded.
  • The semantic network consists of interconnected anterior, lateral, and inferior temporal; dorsolateral prefrontal; and lateral parietal regions.
  • Procedural memory is a memory system for motor skills. The structures that are involved in procedural memory include the supplementary motor cortex, superior parietal lobule, basal ganglia, and cerebellum.
  • A suboptimal level of consciousness, alertness, attention, language, or neurovisual function can affect memory performance.
  • Neuropsychological testing objectively evaluates the performance of different cognitive domains (including memory).
  • Amnesias are divided into anterograde and retrograde. Retrograde amnesias frequently have a temporal gradient; memories that were formed closer to an insult are more likely to be forgotten than memories formed further from the insult.
  • Amnesias can be also divided into acute and nonacute. Acute amnesias can be further divided into persistent and transient.
  • Working memory dysfunction can be seen in many neurologic and psychiatric conditions.
  • Impaired retention of episodic memory can be seen when pathologic processes affect the medial temporal lobe and related limbic structures. Clinically, it presents with a rapid decay of newly learned information.
  • Impaired encoding or retrieval of episodic memory or both can be observed when pathologic processes affect the medial temporal lobe, executive networks, or both. Clinically, impaired encoding presents with a diminished ability to register new information. Impaired retrieval presents with the impaired active recall of encoded information, with at least partially preserved recognition of the information that was originally presented.
  • Impaired semantic memory can present when the pathologic process affects the main hubs of the semantic network. Clinically, it presents with the loss of word, object, and concept meaning.

Article 4: Primary Progressive Aphasia and Stroke Aphasia

Murray Grossman, MDCM, FAAN; David J. Irwin, MD. Continuum (Minneap Minn). June 2018; 24 (3 Behavioral Neurology and Psychiatry):745–767.

ABSTRACT

PURPOSE OF REVIEW

This article summarizes the clinical and anatomic features of the three named variants of primary progressive aphasia (PPA): semantic variant PPA, nonfluent/agrammatic variant PPA, and logopenic variant PPA. Three stroke aphasia syndromes that resemble the PPA variants (Broca aphasia, Wernicke aphasia, and conduction aphasia) are also presented.

RECENT FINDINGS

Semantic variant PPA and Wernicke aphasia are characterized by fluent speech with naming and comprehension difficulty; these syndromes are associated with disease in different portions of the left temporal lobe. Patients with nonfluent/agrammatic variant PPA or Broca aphasia have nonfluent speech with grammatical difficulty; these syndromes are associated with disease centered in the left inferior frontal lobe. Patients with logopenic variant PPA or conduction aphasia have difficulty with repetition and word finding in conversational speech; these syndromes are associated with disease in the left inferior parietal lobe. While PPA and stroke aphasias resemble one another, this article also presents their distinguishing features.

SUMMARY

Primary progressive and stroke aphasia syndromes interrupt the left perisylvian language network, resulting in identifiable aphasic syndromes.

KEY POINTS

  • Aphasia is a central disorder of language comprehension and expression that cannot be attributed to a peripheral sensory deficit (such as reduced auditory acuity) and is not due to a peripheral motor disorder (such as weakness of the muscles of articulation) that may mimic aphasia.
  • Primary progressive aphasia refers to a group of focal neurodegenerative syndromes primarily affecting language.
  • The diagnosis of primary progressive aphasia requires that the language impairment is the primary cognitive deficit and that it is progressive in nature.
  • The manifestations of aphasia due to stroke appear suddenly, not gradually as in primary progressive aphasia.
  • It is valuable to recognize each of the primary progressive aphasia syndromes since they may be markers of a statistically increased risk of a specific form of frontotemporal lobar degeneration pathology, and it is valuable clinically to recognize the forms of stroke aphasia since they are often associated with an embolic stroke that may have its origins in the heart.
  • Long-term memory for concepts, such as knowledge of objects, actions, and ideas, is represented in semantic memory, and this appears to be compromised in semantic variant primary progressive aphasia.
  • One major clinical feature of semantic variant primary progressive aphasia is profound confrontation naming difficulty. Patients are severely impaired at naming pictured objects or using these words in spontaneous speech. A second major clinical feature is impaired comprehension of single words.
  • Since the problem in semantic variant primary progressive aphasia appears to affect both the comprehension and expression of single words, the core deficit is thought to involve semantic memory.
  • It appears that patients with semantic variant primary progressive aphasia are disproportionately impaired in their ability to understand and name object concepts.
  • Despite their approximate comprehension of single words, patients with Wernicke aphasia tend to have relatively preserved comprehension of objects.
  • Patients with Wernicke aphasia typically have difficulty with repetition, whereas this is rarely evident in semantic variant primary progressive aphasia until the patient becomes quite impaired.
  • Patients with Wernicke aphasia have relatively preserved oral reading, whereas semantic variant primary progressive aphasia is associated with a specific disorder of reading known as surface dyslexia.
  • Surface dyslexia refers to difficulty reading sight vocabulary words. Patients with surface dyslexia instead use their preserved letter-sound correspondence rules to sound out sight words, for example, reading dough as dog.
  • Imaging studies associate semantic variant primary progressive aphasia with atrophy of left anterior and ventral gray matter regions of the temporal lobe as well as the anterior hippocampus and the amygdala.
  • Right anterior temporal lobe disease in frontotemporal lobar degeneration is associated with behavioral abnormalities and the behavioral variant frontotemporal dementia syndrome, and patients with semantic variant primary progressive aphasia often develop additional right temporal (and frontal) disease along with a social disorder clinically consistent with behavioral variant frontotemporal dementia during the natural history of disease.
  • Imaging studies have related difficulty with semantically mediated tasks directly to left anterior and ventral temporal gray matter disease in semantic variant primary progressive aphasia.
  • Patients with semantic variant primary progressive aphasia frequently have pathology that is associated with the accumulation of transactive response DNA-binding protein 43, an RNA-binding protein that functions normally in the nucleus to help regulate DNA and RNA processing.
  • Semantic memory difficulty resembling semantic variant primary progressive aphasia due to other causes may be encountered, such as in herpes encephalitis, but these are often subacute in onset and do not have the slow evolution of semantic variant primary progressive aphasia. Some forms of closed head trauma may resemble semantic variant primary progressive aphasia, but these are easily distinguished by their sudden onset and nonprogressive course.
  • In contrast to the anterior and ventral temporal anatomic distribution of disease in semantic variant primary progressive aphasia, more posterior and superior areas of the temporal lobe are compromised in Wernicke aphasia.
  • The clinical hallmark of nonfluent/agrammatic primary progressive aphasia is slowed, effortful, nonfluent speech.
  • One essential characteristic of speech in nonfluent/agrammatic primary progressive aphasia is its impoverished grammatical features.
  • It is important to distinguish the nonfluent speech associated with the grammatical simplifications and errors seen in nonfluent/agrammatic primary progressive aphasia from the pattern of reduced speech output seen in fluent forms of aphasia, in which searching for words can slow speech output in the absence of grammatical deficits.
  • Apraxia of speech involves impaired coordination and planning of the motor articulators. Clinical characteristics of apraxia of speech include the production of incorrect speech sounds and sequences of sounds that do not occur in the speaker’s native language, groping for the correct sound although not necessarily producing the intended target after several attempts, and oddly placed pauses in the speech stream.
  • Patients with nonfluent/agrammatic primary progressive aphasia are impaired in their oral grammatical comprehension.
  • Patients with nonfluent/agrammatic primary progressive aphasia have some working memory and executive deficits on nonlinguistic measures, such as reverse digit span and category naming fluency.
  • Patients with Broca aphasia have slowed, effortful speech.
  • Nonfluent/agrammatic primary progressive aphasia may include apraxia of speech, while this appears to occur much less often in Broca aphasia. An impairment of repetition is less common in nonfluent/agrammatic primary progressive aphasia, while Broca aphasia is often associated with impaired repetition.
  • Structural MRI studies emphasize gray matter atrophy in the inferior frontal region of the left hemisphere in nonfluent/agrammatic primary progressive aphasia.
  • Sentence comprehension appears to be related to regional gray matter atrophy in left inferior and dorsolateral prefrontal regions in nonfluent/agrammatic primary progressive aphasia.
  • Neurodegenerative disease, such as that found in nonfluent/agrammatic primary progressive aphasia, interrupts large-scale neural networks; this is emphasized by the disease found in white matter projections between the gray matter areas of the language network in nonfluent/agrammatic primary progressive aphasia.
  • Nonfluent/agrammatic primary progressive aphasia is most often associated with forms of frontotemporal lobar degeneration involving the accumulation of the microtubule-associated protein tau, as seen at autopsy.
  • Broca aphasia due to stroke is often associated with ischemia centered in the left inferior frontal lobe.
  • The current clinical criteria for logopenic variant primary progressive aphasia include core elements of lexical retrieval difficulties in spontaneous speech and impaired repetition, with supportive features of phonologic paraphasic errors or speech-sound substitutions and the absence of motor speech difficulties and single-word/object comprehension difficulties.
  • Patients with logopenic variant primary progressive aphasia resemble patients with nonfluent/agrammatic primary progressive aphasia in that they may also have slowed, hesitant speech because of circumlocutions and lexical retrieval difficulties that can superficially resemble nonfluent/agrammatic primary progressive aphasia. However, the quantitative rate of speech production is about 90 words per minute, or about twice the rate of nonfluent/agrammatic primary progressive aphasia.
  • The often-severe word-finding difficulty with circumlocutory speech in logopenic variant primary progressive aphasia may be difficult to distinguish from the single-word expression difficulties found in semantic variant primary progressive aphasia.
  • Patients with logopenic variant primary progressive aphasia have preserved knowledge of objects.
  • The key feature of conduction aphasia is a profound repetition deficit.
  • Patients with logopenic variant primary progressive aphasia have atrophy in the inferior parietal and posterior temporal lobes.
  • Studies using in vivo positron emission tomography imaging of amyloid pathology find a high rate of Alzheimer disease pathology in patients with logopenic variant primary progressive aphasia.
  • Logopenic variant primary progressive aphasia diagnostic criteria are relatively specific for underlying Alzheimer disease pathology but are less sensitive since many patients with primary progressive aphasia with Alzheimer disease pathology do not meet criteria for logopenic variant primary progressive aphasia because of either the absence of core clinical criteria of difficulty in repetition or the presence of additional motor speech or semantic features.
  • Conduction aphasia following stroke, from the classic connectionist perspective, is associated with damage to the arcuate fasciculus, the white matter that carries projections between the inferior parietal and superior temporal region known as the Wernicke area and the inferior frontal region known as the Broca area.
  • Distinctions between progressive and stroke forms of aphasia may be due, in part, to the anatomic locus of disease.

Article 5: Apraxia, Neglect, and Agnosia

H. Branch Coslett, MD, FAAN. Continuum (Minneap Minn). June 2018; 24 (3 Behavioral Neurology and Psychiatry):768–782.

ABSTRACT

PURPOSE OF REVIEW

In part because of their striking clinical presentations, disorders of higher nervous system function figured prominently in the early history of neurology. These disorders are not merely historical curiosities, however. As apraxia, neglect, and agnosia have important clinical implications, it is important to possess a working knowledge of the conditions and how to identify them.

RECENT FINDINGS

Apraxia is a disorder of skilled action that is frequently observed in the setting of dominant hemisphere pathology, whether from stroke or neurodegenerative disorders. In contrast to some previous teaching, apraxia has clear clinical relevance as it is associated with poor recovery from stroke. Neglect is a complex disorder with many different manifestations that may have different underlying mechanisms. Neglect is, in the author’s view, amulticomponent disorder in which impairment in attention and arousal is a major contributor. Finally, agnosias come in a wide variety of forms, reflecting impairments ranging from low-level sensory processing to access to stored knowledge of the world (semantics).

SUMMARY

The classic behavioral disorders reviewed here were of immense interest to early neurologists because of their arresting clinical phenomenology; more recent investigations have done much to advance the neuroscientific understanding of the disorders and to reveal their clinical relevance.

KEY POINTS

  • Ideomotor apraxia is conceptualized as a loss of knowledge regarding skilled action. Ideational apraxia is often considered to be a disorder of planning and sequencing that is most apparent in multistep actions, such as preparing a letter to be mailed.
  • The ventrodorsal and dorso-dorsal streams are particularly important in the production of meaningful and meaningless gestures, respectively.
  • Apraxia is best assessed by asking the patient to execute an action to command or, if unable to do so, to imitate a meaningful gesture made by the examiner.
  • Inability to imitate meaningless body postures or gestures is not a disorder of skilled action but reflects an impairment in the procedures for translating visual information into motor coordinates.
  • Hemispace refers to the side of a person’s environment and may be defined with respect to at least three axes: head, body, and eye position. Manifestations of neglect may be influenced by all three coordinate frames.
  • Results of tests for neglect are very frequently influenced by the location of the stimulus or response; for example, patients may extinguish tactile stimuli on the left hand when it is located in left hemispace but not when it is in right hemispace.
  • A wide range of phenomena, such as extinction, are commonly observed in neglect but may dissociate and are not considered by many to be a core part of neglect.
  • Neglect is a heterogeneous and multicomponent disorder of which attentional asymmetries and disorders of arousal are common components.
  • Neglect may be assessed with a wide range of bedside tasks and formal batteries. It is important to note, however, that careful observation of the patient may reveal subtle deficits that bedside tasks, such as line bisection, do not identify.
  • Extinction may be observed in vision, touch, and audition independently or in combination. Stimuli that are near the detection threshold are more likely to identify extinction.
  • Neglect is most frequently associated with lesions in the right parietal lobe but may be caused by pathology in a distributed attentional network that includes the right inferior frontal lobe, thalamus, basal ganglia, and white matter tracts connecting them.
  • In the traditional nosology, apperceptive agnosias result from a failure in sensory processing, whereas associative agnosias are caused by a failure to contact stored information about an object after an adequate perceptual representation has been constructed.
  • Prosopagnosia is a disorder of visual recognition specific to faces. In this disorder, which may be either acquired or developmental, patients often recognize a face as a face and, in some instances, derive substantial information about the stimulus such as age, gender, and emotional expression but are unable to identify the individual.
  • Agnosias may be distinguished by the specific nature of the stimuli rather than the sensory modality of the input; for example, in the visual domain, material-specific agnosias are observed that selectively impair recognition of faces or words.
  • Pure word deafness is a disorder in which patients can identify environmental sounds (eg, a car horn, a telephone ringing) but cannot understand speech despite at least largely normal ability to read, write, and speak.
  • Modality-specific agnosias are disorders of recognition that involve one type of sensory input, such as vision, audition, or touch.
  • Patients with posterior cortical atrophy may have problems recognizing faces, words, and objects and are particularly impaired in the recognition of complex scenes, often showing elements of Balint syndrome.
  • Posterior cortical atrophy is caused by Alzheimer disease in approximately two-thirds of patients but is also caused by dementia with Lewy bodies, corticobasal degeneration, and prion diseases.
  • Visual agnosias are frequently observed in Alzheimer disease and frontotemporal dementia.
  • Recognition is a complex process that should be assessed by more than simply asking patients to name an object; patients may also be asked to point to named objects and to demonstrate the manner in which an object may be used.

Article 6: Aggression and Agitation in Dementia

M. Uri Wolf, MD, FRCPC; Yael Goldberg, PhD, CPsych; Morris Freedman, MD, FRCPC, FAAN. Continuum (Minneap Minn). June 2018; 24 (3 Behavioral Neurology and Psychiatry):783–803.

ABSTRACT

PURPOSE OF REVIEW

This article reviews the treatment of aggression and agitation in dementia. Both nonpharmacologic and pharmacologic approaches to responsive behaviors are discussed. Practical treatment strategies are applied to common behavioral symptoms.

RECENT FINDINGS

Aggressive and agitated behavior is common in dementia. Behavioral symptoms lead to reduced quality of life and distress for both patients and caregivers. They can also lead to poor outcomes and are associated with significant financial implications for the individual and health care system. A wide range of difficult behaviors exists, with limited evidence for deciding on treatment. Clinicians should integrate the available evidence with practical and commonsense strategies to target these difficult-to-treat behaviors.

SUMMARY

Treating aggression and agitation in dementia is challenging. Viewing behaviors as a response to either internal or external stimuli can help guide treatment. Treatment should emphasize nonpharmacologic approaches as an initial step, using practical and commonsense strategies. Caregivers and family should be actively involved in the planning and implementation of behavioral plans. It is essential to minimize both medical and nonmedical factors that may be contributing to behaviors. When pharmacologic options are required, it is important to choose medications thatwill target specific behavioral goals, having both practical consideration and the best evidence in mind.

KEY POINTS

  • To develop an effective intervention, it is important to view difficult behaviors as a response to a stimulus in the patient’s internal or external environment.
  • Before treating responsive behavior, it is important to accurately define and describe the nature and magnitude of the problem.
  • Obtaining collateral information from multiple sources who are involved with the patient will give a richer and more accurate history.
  • Using formal assessment tools to measure and track behavior can inform behavior management.
  • Whenever possible, nonpharmacologic interventions should be tried before pharmacologic interventions.
  • Using some creativity can allow for simple, but effective, nonpharmacologic interventions.
  • Nonpharmacologic interventions should be tailored to suit the patient, caregivers, and environment.
  • Evaluating the outcome of nonpharmacologic interventions will help determine if they have been helpful or if modifications should be made.
  • The pharmacologic approach to treating responsive behavior includes using the best evidence available but also improvising when evidence is lacking.
  • It is important to titrate medications slowly and monitor for adverse effects or worsening of behavior.
  • Deciding which behavior to target first requires prioritizing safety concerns and patient and caregiver distress as well as understanding the factors contributing to the behavior.
  • If environmental factors are triggering behaviors, reducing the impact of the environment on the patient or modifying the environment may be helpful.
  • Disruptive behavior can be an expression of either physical or emotional discomfort.
  • It is important to reduce or eliminate medications that may be contributing to disruptive behavior.
  • Avoidant and resistive behaviors can be driven by medical contributors such as pain, infection, and swallowing difficulties or by neuropsychiatric contributors such as depression and psychosis.
  • Treating behaviors that prevent provision of personal care requires looking for compromises in nonessential tasks and providing education to family and caregivers.
  • Perseverative and repetitive behaviors can be related to physical or emotional discomfort or to sensory deprivation.
  • Disinhibited and hypersexual behaviors can be driven by need for affection and intimacy and mediated by difficulties with judgment.
  • When hyperoral behavior is present, it is essential to ensure that the environment is safe from objects that can be harmful if ingested.
  • Psychotic symptoms that are not distressing or harmful to others do not need to be treated.
  • It is not useful to argue with patients about the veracity of hallucinations and delusions.

Article 7: Mood Disorders

Jeffrey Rakofsky, MD; Mark Rapaport, MD. Continuum (Minneap Minn). June 2018; 24 (3 Behavioral Neurology and Psychiatry):804–827.

ABSTRACT

PURPOSE OF REVIEW

This article discusses the prevalence of the major mood disorders (major depressive disorder and bipolar disorder) in the community and within neurologic settings, articulates the steps taken to make a diagnosis of major depressive disorder or bipolar disorder, and reviews old and newer treatment options with proven efficacy for the treatment of these two conditions.

RECENT FINDINGS

New medications are available as treatment options for major depressive disorder and bipolar disorder, such as intranasal and IV ketamine, and somatic treatments, such as deep brain stimulation and vagal nerve stimulators, are being used to target treatment-resistant depression.

SUMMARY

Mood disorders are common in neurologic settings. They are disabling and increase morbidity and mortality. Clinicians should have a high index of suspicion if they suspect their patients seem more distressed or incapacitated than would be warranted by their neurologic disorders. If a patient does have a mood disorder, validating the patient’s experience, initiating treatment, and, if necessary, referring the patient to a primary care physician or psychiatrist are appropriate steps.

KEY POINTS

  • Within primary care settings, 13% to 17% of patients screen positive for symptoms of depression, while 33% of patients seen in a neurologic outpatient setting screen positive for depressive symptoms.
  • Genetic studies have revealed a heritability of 37% and a 2.8 times increased risk for developing major depressive disorder among first-degree relatives of probands with major depressive disorder.
  • Among patients who have recovered from their first manic episode, 40% will have a recurrence into depression or mania within the subsequent 2 years.
  • Nearly 75% of people with a lifetime history of major depressive disorder will have another psychiatric illness at some point in their lives.
  • It is now thought that our current construct of major depressive disorder encompasses a complex heterogeneous syndrome in which multiple different defects can lead to a cascade of events that cause the development of a depressive endophenotype.
  • One refinement of the criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) is the elimination of an arbitrary rule that prevented clinicians from diagnosing major depressive disorder in an individual who presented with symptoms within the first 2 months after the death of a loved one.
  • Polysomnography is only ordered in cases in which the physician suspects a primary sleep disorder may be present in addition to major depressive disorder.
  • Patients with a history of depression have a twofold greater risk of developing irreversible dementia, and a large number of those with depression with reversible dementia will progress to irreversible dementia within 2 to 3 years.
  • Physical fatigue is a symptom commonly reported by patients with major depressive disorder or bipolar disorder, and it can present as low energy, decreased physical endurance, tiredness, increased effort with physical tasks, weakness, or sluggishness.
  • The clinician should distinguish suicide attempts from other acts of self-harm in which the intent is not death but another purpose, such as the elimination of anxiety, resolution of a sense of emptiness, a desire for a sense of control, or mitigating a feeling of intense rage.
  • Increased risks of suicide attempt and completion have been reported for patients with neurologic illnesses such as multiple sclerosis, epilepsy, Huntington disease, dementia, traumatic brain injury, and migraine with aura, while Parkinson disease has been associated with increases in suicidal ideation but not attempts.
  • Several neurologic illnesses can induce symptoms by their impact on mood regulatory components of the brain and monoamine production.
  • The mental status examination is only one small part of the data that should be gathered to make an accurate diagnosis of major depressive disorder.
  • First-line treatments for major depressive disorder include depression-focused psychotherapy, pharmacotherapy, the combination of psychotherapy and medications, or somatic treatments, such as bright light therapy.
  • Neurologists may or may not choose to initiate pharmacologic treatment for a patient’s major depressive disorder. Those who identify the illness in a patient and choose not to treat should, at minimum, provide psychoeducation to the patient, normalizing the major depressive disorder symptoms in the context of having a neurologic illness.
  • After psychoeducation, neurologists should refer patients with major depressive disorder to a primary care physician or psychiatrist for treatment.
  • If the neurologist suspects a patient has undiagnosed bipolar disorder, the patient should always be referred to a psychiatrist.
  • Psychotherapy is particularly useful for individuals with major depressive disorder who cannot tolerate medications and who may also be dealing with the losses (eg, independence, functioning) that come with comorbid neurologic illnesses.
  • The different classes of antidepressants include selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), atypical antidepressants, tricyclic antidepressants, and monoamine oxidase inhibitors (MAOIs)
  • The first-line medications used in bipolar disorder are mood stabilizers, which include lithium, and the anticonvulsants valproate, carbamazepine, and lamotrigine.
  • Regardless of the antidepressant selected, one must be careful about adding an antidepressant to a Parkinson disease regimen that already includes a high dose of the monoamine oxidase inhibitor selegiline, as serotonin syndrome or hypertensive crises could ensue.
  • When treating patients with epilepsy, antidepressants that lower the seizure threshold, including tricyclic antidepressants and bupropion, should be avoided.
  • Somatic treatments are nonpharmacologic interventions that involve the application of physical forces (eg, light, electricity, magnetism) to induce neurochemical changes within specific regions of the brain.
  • Bright light therapy is expected to modulate the patient’s chronobiological cycle, which induces antidepressant effects both in those with and those without seasonal-onset variants of major depressive disorder.

Article 8: Obsessive-Compulsive Disorder

Peggy M. A. Richter, MD, FRCPC; Renato T. Ramos, MD. Continuum (Minneap Minn). June 2018; 24 (3 Behavioral Neurology and Psychiatry):828–844.

ABSTRACT

PURPOSE OF REVIEW

This article reviews current knowledge regarding diagnosis, pathophysiology, and treatment trends in obsessive-compulsive disorder (OCD), a severe, underrecognized, and chronic condition frequently encountered in neurologic practice.

RECENT FINDINGS

With a lifetime prevalence estimated at 2.5%, OCD is a common condition that can also present comorbidly with neurologic disease. The core symptoms of OCD are obsessions and compulsions. Obsessions are intrusive repetitive thoughts, urges, images, or impulses that trigger anxiety and that the individual is not able to suppress. Compulsions are repetitive behaviors or mental acts occurring in response to an obsession with the intention of reducing the distress caused by obsessions. Neuroimaging, neuropsychological, and pharmacologic studies suggest that the expression of OCD symptoms is associated with dysfunction in a cortico-striato-thalamo-cortical circuit. Evidence-based treatments for OCD comprise pharmacotherapy and cognitive-behavioral therapy. Selective serotonin reuptake inhibitors (SSRIs) are the first-line drugs recommended for OCD, but significant differences exist in their use for OCD compared to their use for other mood and anxiety conditions, including the need for higher dosage, longer trials necessitated by a longer lag for therapeutic response, and typically lower response rates. Cognitive-behavioral therapy, based on the principles of exposure and response prevention, shows results superior to pharmacologic treatments with lower relapse rates on long-term follow-up and thus should be considered in the treatment plan of every patient with OCD.

SUMMARY

OCD and obsessive-compulsive symptoms are frequently encountered in the neurologic clinic setting and require a high index of suspicion to effectively screen for them and an illness-specific therapeutic approach.

KEY POINTS

  • The lifetime prevalence for obsessive-compulsive disorder is estimated at 1% to 3%, with a bimodal pattern of onset; symptoms start during childhood/adolescence more frequently in males, while early adulthood onset is more common among women.
  • Obsessions are intrusive repetitive thoughts, urges, images, or impulses that trigger anxiety and that the individual is not able to suppress.
  • Compulsions are repetitive behaviors or mental acts occurring in response to an obsession that must be done according to rigid rules to reduce the distress caused by obsessions.
  • Patients with obsessive-compulsive disorder can present with variable insight, ranging from good insight with full appreciation of the excessive/irrational nature of the symptoms to frankly delusional.
  • The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) lists obsessive-compulsive disorder in the category “Obsessive-Compulsive and Related Disorders,” which also includes hoarding disorder, body dysmorphic disorder, excoriation (skin-picking) disorder, and trichotillomania (hair-pulling) disorder.
  • Individuals presenting exclusively with hoarding difficulties in the absence of frank obsessions or compulsions should not be diagnosed with obsessive-compulsive disorder but rather with hoarding disorder.
  • It is important to differentiate between obsessive-compulsive disorder and the obsessive-compulsive–related disorders as significant differences in the treatment approach are needed for each of these conditions.
  • Obsessive-compulsive disorder is a frequent comorbid condition in Huntington disease, stroke, Parkinson disease, Sydenham chorea, traumatic brain injury, and Tourette syndrome.
  • Neuroimaging and neuropsychological studies suggest that the expression of obsessive-compulsive disorder symptoms is associated with dysfunction in a cortico-striato-thalamo-cortical circuit.
  • Neuroimaging is not currently recommended routinely for evaluation of individuals with obsessive-compulsive disorder.
  • Obsessive-compulsive disorder is associated with a cluster of neurocognitive deficits, including difficulties in set-shifting and response inhibition.
  • Psychoeducation is crucial in treating patients with obsessive-compulsive disorder because of the stigma associated with the illness and the general lack of knowledge in the community and because it will enhance treatment compliance.
  • Selective serotonin reuptake inhibitors are the first-line pharmacologic treatment for obsessive-compulsive disorder. They are generally very safe and well tolerated and will also work for the mood and anxiety disorders frequently comorbid with obsessive-compulsive disorder.
  • Pharmacologic treatment of obsessive-compulsive disorder distinctly differs from other mood and anxiety disorders, requiring a higher dose for the best likelihood of response and longer trials to accommodate the longer therapeutic lag (typically 6 to 10 weeks) in obsessive-compulsive disorder.
  • A lack of response or partial response is more common in obsessive-compulsive disorder than in other psychiatric conditions. In individuals who are unresponsive, guidelines suggest trying two different selective serotonin reuptake inhibitors sequentially, then moving on to a second-line option, such as clomipramine or venlafaxine. Augmentation with atypical antipsychotics is also an option.
  • It is generally recommended that patients continue on medication for a minimum of 1 year after achieving a good therapeutic response, as obsessive-compulsive disorder is associated with a very high relapse rate following medication discontinuation.
  • Cognitive-behavioral therapy is the most effective treatment in obsessive-compulsive disorder. It is based on the principles of exposure to anxiety-provoking triggers without performance of rituals (often referred to as exposure and response prevention).
  • For extremely severe and refractory cases, neuromodulatory treatments with varying degrees of invasiveness can be helpful for obsessive-compulsive disorder. Referral to a tertiary care center with specific expertise in obsessive-compulsive disorder should be sought for these individuals.

Article 9: Psychosis

Lindsey A. Schrimpf, MD; Arpit Aggarwal, MD; John Lauriello, MD. Continuum (Minneap Minn). June 2018; 24 (3 Behavioral Neurology and Psychiatry):845–860.

ABSTRACT

PURPOSE OF REVIEW

Psychosis is a psychiatric condition that has significant overlap with neurologic disease. This article is intended to educate the neurologist on the psychiatric manifestations of psychosis and its evaluation, diagnosis, and treatment. How to differentiate a primary psychiatric cause of psychosis from psychosis secondary to a medical or neurologic condition is also reviewed.

RECENT FINDINGS

Current research in psychotic disorders has focused increasingly on negative symptoms and cognitive impairment in psychotic illness, as it is now recognized that these cause the greatest impact on functional deficits for patients. A number of new medications have also been introduced to target negative symptoms and cognitive deficits in psychotic illness. These have new implications in terms of treatment overlap with medications being prescribed by providers in psychiatry, neurology, and general practice.

SUMMARY

This article discusses the current methods for evaluating, diagnosing, and treating psychosis. Psychosis as a primary mental health disorder is a diagnosis of exclusion, as psychosis can be a direct symptom of underlying medical or neurologic disease. Deliriumand dementia are the two most important disorders to rule out. This article will help readers be more prepared to assess and treat the patient with psychosis.

KEY POINTS

  • The five domains of psychological functioning affected by schizophrenia and other psychotic disorders are delusions, hallucinations, disorganized thinking (speech), grossly disorganized or abnormal motor behavior (including catatonia), and negative symptoms.
  • Delusions are fixed beliefs that a patient will maintain despite conflicting evidence offered by those around them. The delusions may be persecutory, referential, somatic, religious, or grandiose in nature.
  • With religious delusions, it is important to differentiate between culturally appropriate beliefs and delusions.
  • Hallucinations are perceptual experiences that are very vivid and real to the individual experiencing them. They are not under voluntary control and can occur in any sensory modality.
  • It is important to recognize that visual hallucinations can be a component of psychosis, but many times, especially if onset is acute, visual hallucinations are an indicator for delirium, dementia, or other neurologic disorders.
  • Tactile, olfactory, and gustatory hallucinations are unusual in a primary psychotic disorder, and their presence suggests another underlying medical or neurologic cause.
  • Negative symptoms include diminished emotional expression, avolition (a lack of motivation), alogia (poverty of speech), anhedonia (lack of the ability to experience pleasure), and asociality. It is now recognized that negative symptoms gravely impair an individual’s ability to function productively in society.
  • Functional status (psychosocial functioning) has been shown to have a greater relationship to functional outcomes in schizophrenic patients than disorder status (the presence of psychotic symptoms). In particular, social cognition is a major determinant of functional status.
  • A positive therapeutic alliance is vital to a successful relationship with a psychotic patient. Research shows that a positive therapeutic relationship in which the patient is involved in the decision making and mutual respect exists between patient and clinician can dramatically impact treatment compliance and patient outcomes.
  • For the nonpsychiatric clinician, one of the most important goals in the interview of patients who present with acute-onset psychosis or are experiencing a change in the symptoms of their psychosis is to establish whether the symptoms are related to a primary psychotic disorder or secondary to an underlying medical or neurologic disease. Establishing a primary psychotic disorder diagnosis is a diagnosis of exclusion.
  • An important but subtle distinction in the cognitive evaluation of the patient with psychosis is that the patient’s ability to remain oriented to his or her surroundings is not impaired in primary psychosis. A patient can be floridly psychotic and still remain oriented to person, place, and time.
  • Evaluating a patient’s cognitive status is an essential component in differentiating primary psychosis from secondary psychosis.
  • The mental status examination takes careful note of the patient’s physical appearance, behavior, mood, speech patterns, thought content, thought processes, cognition, insight, and judgment.
  • Antipsychotic medications are the mainstay of the treatment for psychosis and should be started promptly after an accurate diagnosis has been established.
  • The choice of an antipsychotic medication is primarily based on adverse effects and cost considerations, as they do not differ significantly as far as efficacy is concerned (with the exception of clozapine, which has consistently been shown to be more effective than other oral antipsychotics).
  • Clozapine is effective in reducing suicidal behaviors in patients with schizophrenia and is also effective for psychotic symptoms associated with Parkinson disease. Clozapine can cause granulocytopenia or agranulocytosis in approximately 1% of patients, requiring regular blood cell count monitoring.
  • Although antipsychotic medications remain the mainstay of treatment for psychosis, most patients require one or more additional strategies, such as providing education and information about the disease, social skills training, cognitive-behavioral therapy, assertive community treatment, or problem-solving family therapy.

Article 10: Conversion Disorder

Anthony Feinstein, MD, PhD. Continuum (Minneap Minn). June 2018; 24 (3 Behavioral Neurology and Psychiatry):861–872.

ABSTRACT

PURPOSE OF REVIEW

This article provides a broad overview of conversion disorder, encompassing diagnostic criteria, epidemiology, etiologic theories, functional neuroimaging findings, outcome data, prognostic indicators, and treatment.

RECENT FINDINGS

Two important changes have been made to the recent Diagnostic and StatisticalManual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria: the criteria that conversion symptoms must be shown to be involuntary and occurring as the consequence of a recent stressor have been dropped. Outcome studies show that the rate of misdiagnosis has declined precipitously since the 1970s and is now around 4%. Functional neuroimaging has revealed a fairly consistent pattern of hypoactivation in brain regions linked to the specific conversion symptom, accompanied by ancillary activations in limbic, paralimbic, and basal ganglia structures. Cognitive-behavioral therapy looks promising as the psychological treatment of choice, although more definitive data are still awaited, while preliminary evidence indicates that repetitive transcranial magnetic stimulation could prove beneficial as well.

SUMMARY

Symptoms of conversion are common in neurologic and psychiatric settings, affecting up to 20% of patients. The full syndrome of conversion disorder, while less prevalent, is associated with a guarded prognosis and a troubled psychosocial outcome. Much remains uncertain with respect to etiology, although advances in neuroscience and technology are providing reproducible findings and new insights. Given the confidence with which the diagnosis can be made, treatment should not be delayed, as symptom longevity can influence outcome.

KEY POINTS

  • The diagnosis of conversion disorder depends on the presence of atypical neurologic-type symptoms that do not conform to the known anatomic and physiologic constructs that support neurologic diagnoses.
  • The diagnostic criteria for conversion disorder have been revised recently to reflect two significant conceptual shifts. It is no longer necessary to assert that the symptoms are not intentionally produced or linked to recent stressors.
  • While it is accepted that symptoms of conversion disorder are involuntary and not simulated, their precise origins remain unclear.
  • Given the protean manifestations of conversion, it remains unclear from an etiologic perspective whether a single theory can explain the disorder or whether specific theories are required according to symptom presentation.
  • Rates of misdiagnosis of a neurologic disorder as a conversion disorder have improved considerably over the decades and are now low. Current estimates are approximately 4%.
  • Conversion disorder can still occur in the presence of a confirmed neurologic disorder as long as the signs and symptoms remain atypical and do not conform to established anatomic and physiologic constructs.
  • Findings on functional MRI in patients with conversion disorder are specific to symptom type. Depending on the presenting symptom, the data are consistent in showing hypoactivation of cortical (somatosensory) regions coupled with ancillary activation of limbic and basal ganglia structures.
  • Favorable prognostic signs are early diagnosis and younger age, whereas poor prognostic signs include symptom longevity, attribution of symptoms to physical rather than psychological beliefs, expectations of nonrecovery, and the receipt of illness-related financial benefits.
  • Limited treatment data suggest that cognitive-behavioral therapy can be effective, although findings from a proposed large multicenter randomized controlled trial are still awaited.
  • Training geared toward improving the attitude of primary care providers to patients with conversion disorder may improve outcomes.
  • Much remains unknown about conversion disorder, but advances in neuroscience are starting to provide key insights into the functional neuroanatomy of the condition and which therapies work best.

Article 11: Assessment and Management of Posttraumatic Stress Disorder

Janet Ellis, MBBChir, MD, FRCPC; Ari Zaretsky, MD, FRCPC. Continuum (Minneap Minn). June 2018; 24 (3 Behavioral Neurology and Psychiatry):873–892.

ABSTRACT

PURPOSE OF REVIEW

The goal of this article is to increase clinicians’ understanding of posttraumatic stress disorder (PTSD) and improve skills in assessing risk for and diagnosing PTSD. The importance and sequelae of lifetime trauma burden are discussed, with reference to trends in prevention, early intervention, and treatment.

RECENT FINDINGS

PTSD has different clinical phenotypes, which are reflected in the changes in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria. PTSD is almost always complicated by comorbidity. Treatment requires a multimodal approach, usually including medication, different therapeutic techniques, and management of comorbidity. Interest is growing in the neurobiology of childhood survivors of trauma, intergenerational transmission of trauma, and long-termimpact of trauma on physical health.Mitigation of the risk of PTSD pretrauma in the military and first responders is gaining momentum, given concerns about the cost and disability associated with PTSD. Interest is also growing in screening for PTSD inmedical populations, with evidence of improved clinical outcomes. Preliminary research supports the treatment of PTSD with repetitive transcranial magnetic stimulation.

SUMMARY

PTSD is a trauma-related disorder with features of fear and negative thinking about the trauma and the future. Untreated, it leads to ongoing disruption of life due to avoidance, impaired vocational and social functioning, and other symptoms, depending on the phenotype. Despite a theoretical understanding of underlying mechanisms, PTSD remains challenging to treat, although evidence exists for benefit of pharmacologic agents and trauma-focused therapies. A need still remains for treatments that are more effective and efficient, with faster onset.

KEY POINTS

  • Posttraumatic stress disorder is a trauma-related syndrome of chronic distress, reexperiencing the trauma, dissociative features with mood and cognitive changes, hyperarousal, and avoidance.
  • Between 10% and 50% of people who have had exposure to a life-threatening trauma will develop persistent symptoms of posttraumatic stress disorder.
  • A traumatic event should lead a clinician to conduct a focused screen for further vulnerability and relevant symptoms.
  • Pitfalls for clinicians when diagnosing patients with posttraumatic stress disorder include misdiagnosing the trauma (eg, underestimating the impact of an experience of a migraine or intensive care unit admission) and failing to recognize the hidden face of posttraumatic stress disorder in a complicated comorbid clinical picture.
  • Individual vulnerability to posttraumatic stress disorder includes a past history of trauma, any psychiatric disorder, and low social support.
  • When obtaining the history, patients with possible posttraumatic stress disorder should be asked about reexperiencing the trauma through associated thoughts, physiologic response, flashbacks, or nightmares; avoidance of trauma reminders; loss of enjoyment; negative feelings or thinking, a sense of blame and isolation; hyperarousal; irritability; poor sleep; tension; hypervigilance; and reactivity.
  • The different phenotypes of posttraumatic stress disorder make it more difficult to recognize, and symptoms may be masked by comorbid substance use, brain injury, depression, or anxiety disorder.
  • Two phenotypes of posttraumatic stress disorder have been described, dysphoria and emotional numbing, both with reexperiencing, avoidance, and hyperarousal but differing in sleep, irritability, and concentration symptoms.
  • Patients having four or more categories of childhood trauma had a 4 to 12 times greater increased risk for substance abuse, depression, and suicide attempts; a 2 to 4 times greater risk of smoking, 50 or more sexual partners, and sexually transmitted disease; and a 1.4 to 1.6 times greater risk of physical inactivity and morbid obesity.
  • Of deployed US military personnel, 14% to 16% were found to have posttraumatic stress disorder, which was prospectively associated with early-age heart disease mortality among those free of heart disease at baseline.
  • Mild traumatic brain injury confers extra risk of posttraumatic stress disorder, and the combination is synergistic, with evidence of increased symptoms, cognitive impairment, and difficulty in treatment.
  • Learning theory, along with memory engagement, disruption, alteration, and reconsolidation, underpins the use of prolonged exposure therapy for posttraumatic stress disorder.
  • Animal models of posttraumatic stress disorder have elucidated neurobiological underpinnings in humans.
  • Three main brain structures involved in appraising threat and regulating fear have been studied in posttraumatic stress disorder: the prefrontal cortex, the hippocampus, and the amygdala.
  • In posttraumatic stress disorder, the amygdala is mostly hyperactive, promoting an abnormal fear response of hypervigilant and hyperaroused behavior.
  • Reconsolidation of unstable fear memories can lead to ongoing distressing flashbacks that feed into further activation of the amygdala, with reduced prefrontal cortex inhibition. This leads to the trauma memories becoming more intrusive over time, with persistent hyperarousal and distress.
  • Lifetime trauma burden increases the risk for developing acute disabling symptoms of posttraumatic stress disorder in those who have experienced previous trauma or have chronic complex posttraumatic stress disorder.
  • The current understanding of the neurobiology of posttraumatic stress disorder may explain the efficacy of selective serotonin reuptake inhibitors as a partial treatment for posttraumatic stress disorder as they increase plasticity and learning capacity so that memories and danger assessment of trauma-related cues can be altered more easily and sympathetic overdrive is lessened.
  • A broad, evidence-based approach is often needed in the treatment of posttraumatic stress disorder, including managing comorbid psychiatric illness, brain injury, and chronic pain; medication; and using different therapeutic techniques, including prolonged exposure therapy, cognitive processing therapy and eye movement desensitization and reprocessing therapy.
  • The 2017 American Psychological Association guideline for the treatment of posttraumatic stress disorder in adults gives strong recommendation for cognitive-behavioral therapy, cognitive processing therapy, cognitive therapy, and prolonged exposure therapy.
  • Prolonged exposure therapy uses learning theory to extinguish fear from the trauma memory by repeatedly engaging in the memories in a safe environment without a feared outcome.
  • Cognitive processing therapy addresses the distressing thoughts and associated feelings that people may have in response to trauma.
  • Emerging evidence exists for the use of repetitive transcranial magnetic stimulation for posttraumatic stress disorder based on interrupting the brain circuitry of posttraumatic stress disorder (including reducing hyperactivity of the amygdala), facilitating fear extinction capacity, and increasing cognitive control in the salience network.
  • Internet-based cognitive-behavioral therapy using video, audio, and virtual reality has evidence as a preventive intervention early in the posttrauma period.
  • Early posttrauma intervention, such as early brief exposure starting in the emergency department to disrupt memory consolidation by habituating and reducing the fear associated with the trauma memory, has had some success.
  • Interest in how posttraumatic stress disorder impacts the brain in the neurobiology of childhood survivors of trauma and in understanding and preventing intergenerational transmission of trauma is growing.
  • Identifying those at particular risk for posttraumatic stress disorder and screening for symptoms allows for sustainable stepped care, timely interventions, and judicious use of limited resources.
  • Posttraumatic growth describes a philosophical change in worldview after trauma, including increased gratitude to be alive, a sense of connection to others, spiritual well-being, and a sense of clear priority, with constructs of openness, optimism, and social support.
  • Untreated posttraumatic stress disorder is associated with a sense of personal chaos and distress. Patients cannot live normal lives, fully connect in relationships, or function at work and are highly avoidant of internal or external trauma-related cues; their lives become painfully restricted.
  • The downstream health costs, suffering, and disability associated with PTSD make it imperative to continue to research feasible, acceptable, effective, efficient, and accessible treatments for posttraumatic stress disorder from single events as well as repeated childhood trauma.

Article 12: Diagnosis and Management of Anxiety Disorders

Peter Giacobbe, MD, MSc, FRCPC; Alastair Flint, MD, FRCPC, FRANZCP. Continuum (Minneap Minn). June 2018; 24 (3 Behavioral Neurology and Psychiatry):893–919.

ABSTRACT

PURPOSE OF REVIEW

This article provides a synopsis of the current understanding of the pathophysiology of anxiety disorders, the biological and environmental risk factors that contribute to their development and maintenance, a review of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria, and a practical approach to the treatment of anxiety disorders in adults.

RECENT FINDINGS

Despite the ubiquity of anxiety, the evidence is that most individuals with an anxiety disorder are not identified and do not receive guideline-level care. In part, this may be because of the manifold clinical presentations of anxiety disorders and clinicians’ lack of confidence in accurately diagnosing and treating these conditions, especially in nonpsychiatric settings. Anxiety disorders represent the complex interplay between biological, psychological, temperamental, and environmental factors. Converging lines of evidence point to dysfunction in regulating activity in the “threat circuit” in the brain as a putative common pathophysiology underlying anxiety disorders. Evidence-based treatments for anxiety disorders, such as cognitive-behavioral therapy and antidepressant medications, have been shown to regulate activity in this circuit, which consists of reciprocal connections between the dorsomedial prefrontal cortex, insula, and amygdala.

SUMMARY

Anxiety disorders are the most common class of emotional disorders and a leading cause of disability worldwide. A variety of effective treatment strategies are available, which may exert their therapeutic benefits from top-down or bottom-up modulation of the dysfunctional brain activity associated with anxiety disorders.

KEY POINTS

  • Anxiety disorders are the most common class of emotional disorders and an important cause of disability worldwide.
  • The prefrontal cortex, insula, and amygdala are key structures in the pathophysiology of anxiety.
  • Reduction in the activation of the prefrontal cortex–amygdala circuit to aversive stimuli may be a common neurobiological mechanism underlying effective treatments for anxiety.
  • First-degree relatives of those with anxiety disorders have an increased risk of developing any anxiety disorder or major depressive disorder.
  • Anxiety disorders are polygenic, with estimated genetic heritability estimates of between 30% and 50%.
  • Most anxiety disorders have their onset in childhood, and cases of atypical “late-onset” anxiety should be considered as due to medical, substance, or mood disorder factors until proven otherwise.
  • Environmental factors involving danger or threat, such as abuse or parental loss, increase the risk of developing an anxiety disorder later in life.
  • Females are twice as likely to manifest anxiety disorders compared to males.
  • Panic attacks typically present as the perception of frightening physical symptoms, such as racing heart, shortness of breath, and sweating, in the presence of normal vital signs and medical investigations.
  • A pattern of recurrent and uncued panic attacks is necessary for a diagnosis of panic disorder.
  • In the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), the presence of panic disorder is no longer required to make a diagnosis of agoraphobia.
  • Generalized anxiety disorder is associated with high rates of comorbid conditions, such as physical health issues, substance abuse, and mood disorders.
  • Social anxiety disorder is a chronic condition associated with fear of negative appraisal by others, excessive or unrealistic fear of social or performance situations, and intolerance of the possibility of embarrassment or scrutiny by others in social situations.
  • Phobias in childhood may be transient, but those that persist into adulthood will typically remain chronic.
  • Separation anxiety disorder, which is characterized by excessive fear or anxiety regarding separation from attachment figures, has pathophysiologic links to panic disorder and is a new addition to the group of anxiety disorders in DSM-5.
  • The most important step in the treatment of anxiety is the establishment of the diagnosis, which includes an exploration of the nature of the symptoms and an assessment of comorbid medical and psychiatric factors such as mood disorders, suicidality, and substance use.
  • Anxiety disorders are chronic but treatable conditions.
  • Selection of the appropriate treatment modality for anxiety disorders may, in part, be guided by symptom severity and by patient-rated questionnaires, such as the Generalized Anxiety Disorder 7-Item Scale.
  • Education about the nature of anxiety disorders, avoidance of known exacerbating factors, the promotion of healthy coping strategies, and emotional support should be provided to all patients.
  • A stepped-care approach for those with moderate or severe anxiety has been recommended.
  • The routine coadministration of psychotherapy and medications has not been shown to be superior to either approach alone.
  • Robust data exist to support cognitive-behavioral therapy in the treatment of anxiety disorders, whether administered directly by a therapist or via the Internet.
  • US Food and Drug Administration–approved medications for the treatment of anxiety disorders are from four pharmacologic classes: selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, azapirones, and benzodiazepines.
  • To minimize the risk of premature discontinuation of medication, start at a low dose and slowly increase the dose every 2 to 4 weeks up to the therapeutic range.
  • The azapirone medication buspirone has antianxiety effects limited to reduction of worry. As such, it has limited effects for other indications beyond generalized anxiety disorder, although it may be a helpful option when the use of a benzodiazepine is contraindicated.
  • The beta-blocker propranolol may be effective for peripheral manifestations of anxiety (eg, tremor) in those with the performance subtype of social anxiety disorder.
  • The risk of suicide is increased in those with anxiety disorders, especially in cases of a comorbid mood disorder or substance abuse.
  • Benzodiazepines should be avoided in those with alcohol or substance abuse and should be used with caution in the elderly.
  • A lack of response to an adequate course of either psychotherapy or medication should prompt a reexamination of the diagnosis, confirmation of treatment adherence, and ruling out of latent comorbid factors.
  • Options for those with a lack of response to treatment for an anxiety disorder may include (1) switching from medication to psychotherapy or vice versa, (2) combining medication and psychotherapy, (3) switching between antidepressant medication classes, or (4) adding a medication to an antidepressant or psychotherapy to augment its effects.
© 2018 American Academy of Neurology