Stucky

Question 1

Cattell-Horn-Carrol (CHC) model (1993) of intelligence

Answer 1

the most contemporary and currently influential model. was empirically derived via factor analysis and represents the combination of Catell’s and Horn’s Gf-Gc (i.e., fluid intelligence and crystallized intelligence) theory and Carroll’s Three-Stratum Theory. It is a top-down hierarchical model that posits multiple distinct intelligences; 8 relatively broad intelligences, such as Gf and Gc; and approximately 70 other relatively narrow or specific abilities.

Most IQ tests are influenced by this model. They usually have a single IQ score specifying how much overall g a person has, while at the same time permitting identification of the specific abilities making up that g.

Question 2

Theory of Mind

Answer 2

falls under heading of noncognitive factors of intelligence. The ability to make inferences about other people’s intentions, motivations, and emotional states.

Question 3

Intellectual disability

Answer 3

Intellectual disability is a developmental disorder with onset before age 18 requiring a substantially subnormal IQ (i.e., approximately greater than or equal to two standard deviations below the mean), reflecting limitations in general intellectual functioning, combined with significant deficits in two or more adaptive skills.

Question 4

Dementia

Answer 4

A syndrome that stems from a disease or medical condition involving a decline in or loss of general cognitive ability or multiple areas of cognitive impairment of sufficient severity to impair social and or occupational functioning. Performances on tests of general intelligence decline as dementia advances; in cases of Alzheimer’s disease, decline in IQ may not be evident until the middle stages.

Question 5

Savantism

Answer 5

this is a very rare syndrome in which individuals with an intellectual disability or autism spectrum disorder have one or more specific or narrow remarkable talents that exist in stark contrast to their intellectual disability. The cause or causes of savant syndrome are unknown but may be congenital or acquired as a result of central nervous system disease or injury. Savant syndrome is associated with autism, as well as other psychological disorders and CNS injuries or diseases. It is approximately 6 times more common in males than females. Savant skills most commonly involve exceptional memory,that can also involve exceptional calculation, calendar knowledge, artistic, and or language abilities.

Question 6

Concentration

Answer 6

Often used interchangeably with attention. The ability to sustain attention overtime or to mentally manipulate information.

Question 7

Simple attention

Answer 7

Voluntary; capacity; attention to information that is lost if not rehearsed. Tests include digit span and corsi blocks.

Question 8

Focused attention

Answer 8

Ability to allocate and direct attention that is dependent on capacity. Test includes digit symbol coding.

Question 9

Selective attention

Answer 9

Process by which one chooses some information from a missed other surrounding information or distractors.Cancellation tasks.

Question 10

Sustained attention (vigilance- concentration)

Answer 10

Maintaining attention over a period of time. continuous performance tests.

Question 11

Alternating attention

Answer 11

Shifting ones attention back and forth between tasks.Trail making b.

Question 12

Divided attention

Answer 12

Concentrating on more than one task at a time or multiple aspects within a task, referred to as multitasking by some in the lay public. PASAT

Question 13

Posner and Peterson2012 model of attention

Answer 13

This model divides attention into two major areas: posterior and anterior networks. The posterior network has to do with orienting and shifting attention. The anterior system serves as the detection subsystem (or executive attention subsystem) and involves detecting stimuli either from sensory events or from memory. The two networks also interconnect, allowing for completion of multiple aspects of a task, such as both the orienting and detection of a stimulus. A third area, the alerting network (subserved by the ascending reticular activating system [ARAS]), can influence both anterior and posterior or networks, operating at high or low levels of arousal.

Question 14

Processing speed

Answer 14

The speed at which mental activities are performed and is a prominent feature of the brain’s cognitive efficiency, affecting attention as well as other higher order cognitive processes. Processing speed is dependent on neural transmission and integrity and volume of white matter making up cortico-cortical connections. Other brain areas affecting processing speed include basal ganglia, frontal regions, especially dorsolateral prefrontal, and the cerebellum. Tests include coding and PASAT.

Question 15

Attention: Relevant Brain Structures

Answer 15

• A sending reticular activating system (ARAS)- function is arousal and attention
  
  • anterior cingulate (and limbic system) - determines salience of stimuli and associated emotion slash motivation
  • prefrontal- function is response selection, control, sustained attention, focus, switching, searching, and alternating attention.
  • Orbitofrontal- function is the inhibition of responses; Sustained attention
  • dorsolateral frontal- function is initiation of responses; Sustained attention; Shifting attention
  • medial frontal- function is motivation; Consistency of responding;focused attention
  • thalamus- sensory relay between subcortical areas and the cortex. Various nuclei play a role in specific attentional functions
• –pulvinar nuclei- function is extracting information from the target location and filtering distractors
• –superior colliculus- shifting attention; Eye movements
• –inferior colliculus- orientation to auditory stimuli
  
  • inferior and posterior parietal-underlies disengagement from a stimulus and the representation of space; damage is associated with hemispatial inattention or neglect
  • Right hemisphere-special attention; Appreciation of the gestalt; associated with him a spatial inattention or neglect

Question 16

Specific disorders affecting attention

Answer 16

Attentional difficulties are the most common type of cognitive impairment following brain injury or illness because the white matter tracts and structures subsuming these functions are diffusely represented throughout the brain.

• Delirium: Delirium is a disorder marked by waxing and waning deficits and attention, often including increased distractibility, for awareness, and persistent confusion. The primary attentional processes affected our span and arousal.
• ADHD: ADHD is a developmental disorder characterized by inattention, impulsivity, and sometimes hyperactivity. The executive aspects of attention, such as self regulation, as well as sustained attention or primarily affected in ADHD.
  
  • How many spatial inattention AKA neglect: characterized by impairment and awareness of visual and other stimuli on the side contralateral to a brain lesion and is not the result of a primary sensory deficit. Associated features can include anosognosia or denial of illness, Extinction of stimuli, and asomatognosia, or denial of body part. The underlying pathology is most commonly associated with lesions in the temporal parietal region but is not exclusive to this region. Usually the left side of space is affected as a result of a right hemisphere lesion, but the right side of space can be affected with left hemisphere lesions. The type of attention affected is a spatial focused attention and selective attention.
• –Sensory neglect: an acquired inattention or unawareness to part (typically half) of space; as in hemineglect, it is contralateral to the lesion.
• –Motor neglect: Involves a failure to respond or initiate movement (akinesia) to stimuli in contralateral space.
• –Combined sensory- motor neglect: involves both ignoring stimuli and performing fewer movements in contralateral space.

-Traumatic brain injury: moderate to severe TBI often results in reduced arousal, poor attentional capacity, distractibility, impairments and executive aspects of attention, and reduced information- processing speed. Concussion can also temporarily affect working memory, attention, and processing speed.

Other disorders and factors affecting attention: depression and anxiety, fatigue and lack of sleep or sleep disorders, low or poor arousal, environmental factors like noise, and medications are all non-neurological factors that can negatively influence attentional processes. Reduced motivation or effort is another factor that can affect attention. Factors affecting processing speed include those already mentioned, as well as conditions that diffusely impact various brain structures and white matter integrity, such as multiple sclerosis, TBI, vascular cognitive impairment, Parkinson’s disease.

Question 17

Language- definition

Answer 17

a system of communication involving a formal symbolic scheme reliant on phonology and rules of syntax to express lexical or semantic meaning (i.e., using words). The components of language competence comprise four areas: phonology, syntax, semantics, and pragmatics. Language is distinct from speech in that the latter is the physical oral expression of language. At its most basic, language can be seen as comprising expressive and receptive functions, with expressive language controlled by anterior brain regions and receptive language by posterior brain regions of the dominant hemisphere. Despite evidence that the right hemisphere mediates some language function (e.g., prosodic aspects), it is the left hemi in humans that mediates or performs most language function related to semantics and syntactics.

Question 18

Aphasia

Answer 18

Aphasia is an acquired loss or impairment of language following brain damage or disease that comprises a family of clinically diverse disorders that affect the ability to communicate by oral or written language or both. Developmental language disorders such as dyslexia, apraxia of speech, and dysarthria are not aphasic disorders. The primary etiology is stroke with as many as 40% of patients after stroke having some degree of aphasia. Other potential etiologies include neoplasm, intracranial tumor and infection, traumatic injury and other brain diseases affecting language areas, including neurodegenerative diseases, such as frontotemporal dementia.

Question 19

Assessment of aphasia

Answer 19

The different syndromes of aphasia are distinguished best by language symptoms, such as fluency versus non fluency, auditory comprehension, and the ability to repeat, and, to a lesser extent, by agrammatism and disturbances in reading and writing. Diagnosis and localization of the different syndromes can be accomplished with an examination that includes evaluation of both expressive and receptive language, including spontaneous or conversational speech, repetition, auditory comprehension, word finding, reading and writing, and naming.

• Spontaneous speech: can be a listed through simple conversation while interviewing a patient or taking a medical history or by asking for a description of a picture, such as the cookie theft picture in the Boston diagnostic aphasia examination, 3rd edition. Two specific areas must be addressed: form and content.
  
  • Form of speech: refers to whether a patient’s speech is fluent or non fluent and is examined by looking at the effort required to produce speech, the rate of speech, and the melody and the length of phrases.
    
    • In fluent speech (E. G., wernicke’s, transcortical sensory), verbal output is normal, with normal phrase length (more than five or six words between pauses) and with no apparent articulatory difficulty and normal melody, although the speech may be non meaningful with paraphasic errors.
    • In nonfluent aphasic speech (e.g., broca’s, transcortical motor), verbal output is diminished with decreased phrase length (less than three or four words between pauses), laborious articulation, and poor rhythm. Impaired speech initiation and impairment in production of grammatical sequences is common.
  • Content of speech: refers to word choice and syntax and the presence or absence of paraphasic errors in spontaneous speech.
    
    • In fluent aphasic syndromes, word output itself is likely to be normal, but in terms of content may not be informative or convey meaning (“empty”).
    • In non fluent aphasic syndromes, the critical word or words needed to convey meaning can be present but may not be in the correct order and or with the correct grammatical structure. Agrammatism, resulting in an appearance of “telegraphic” speech, can be seen.
• Comprehension of spoken and written language: can be assessed by questions and commands that increase in complexity and examine comprehension of individual words, category- specific information (e.g., letters, colors, body parts), and meaning imparted from syntax and word order. The standard auditory comprehension section of the BDAE for example is comprised of tests of basic word discrimination;-, two-, and then three- step commands; and complex ideational material. To examine comprehension, the examiner must first establish that the patient has a controllable output channel in which to indicate their response, even if it is limited to pointing or yes and no questions. Comprehension difficulties can be of two types: syntactic and lexical/Semantic.
• -Lesions involving anterior speech areas can result in disturbed comprehension of phonological (syntactic) information used to construct word names.
• –Lesions and posterior language areas more often result in disturbed comprehension of the sequencing of meaningful word sounds to convey meaning (lexical/semantic).
  • repetition: is easily tested by beginning with single simple words then multisyllabic words, followed by short sentences and longer sentences, increasing in complexity. Establishing whether or not repetition is intact is important because the ability to repeat typically indicates that the Perisylvian language centers are functional.
  • naming problems or anomia: the terms anomia and dysnomia can be used interchangeably. Anomia can present in all types of aphasia syndromes and can involve problems naming an object, color, and body part or finding a specific word in spontaneous speech. Word finding difficulties can be evident in spontaneous speech when a patient pause is to search for a word or uses too many words to describe something better described in fewer words. This is circumlocution. Or word finding difficulties can be elicited by presenting a stimulus and asking the patient to name it. A nomiya can occur with many of the aphasic syndromes and is therefore not generally useful for localization, but distinctions between anterior and posterior aphasic syndromes can often be made because patients with nonfluent syndromes may have difficulty with naming as a result of initiation or production problems whereas patients with fluent syndromes may have difficulty as a result of selection problems or an inability to find the right word.
  • Reading: reading aloud and reading silently for comprehension should each be tested separately. Examination of reading should begin with single letters and digits, then words and sentences of increasing length and complexity. When the patient does not have expressive language available, the ability to understand what is red can be tested by allowing the patient to match words to pictures. All aphasic syndromes that include severe impairment of auditory language- with the exception of pure word deafness-are almost always also associated with an acquired impairment of reading or alexia. Alexia can be seen in aphasias of all kinds, and it can be seen in isolation, in which case it can be important for localization. That alexia can be seen in isolation without other features of aphasia, including agraphia, suggests that the brain has evolved specific areas required for reading that are separate from other language areas.
  • Writing: can be tested by asking the patient to write single letters and digits, then words and multi digit numbers, and then sentences of increasing length and complexity. writing tasks can involve both writing to dictation and writing based on visual input such as pictures. Agraphia is loss of the ability to write. Paragraph a is rare; It is usually seen in combination with alexia or aphasia. Generally, because of the close relationship between writing and oral language ability, a patient’s writing will be disordered comparable to the disorder in the patient’s speech.

Question 20

Stroke localization and worse outcomes

Answer 20

-strokes affecting both cortical and subcortical structures tend to have the poorest functional outcomes b/c d. Strokes affecting cortex are less disruptive of the multiple systems needed for normal language.

Question 21

Distinguishing Language Characteristics of the Major Aphasic Syndromes

Answer 21

Broca’s: Nonfluent, intact comprehension, impaired repetition, limited naming, limited reading, writing is impaired similar to speech.

Wernicke’s: Fluent, impaired comprehension, repetition, naming, reading, and writing.

Conduction: Fluent, intact comprehension, impaired naming and repetition, impaired writing, intact reading.

Global: Nonfluent and everything is impaired.

Anomic: Fluent, empty, comprehension, reading, and repetition intact, naming impaired, writing impoverished content.

Subcortical: can be fluent or nonfluent, naming impaired, comprehension and repetition are intact, reading and writing can be either.

Transcortical motor: Nonfluent, intact comprehension, reading, repetition, limited naming, impaired writing.

Transcortical sensory: Fluent, echolalic, intact repetition, impaired comprehension, reading, writing, and naming

Transcortical mixed: nonfluent echolalic, repetition intact, everything else impaired.

Question 22

Subcortical Aphasia Syndrome

Answer 22

Refers to language disorders that may arise from lesions to the striatum, internal capsule, or thalamus. These aphasias may share some of the characteristics of the cortical aphasias and may be fluent or nonfluent. When the causative lesion is entirely subcortical, then the prognosis for recovery is good, although some residual speech impairment may be evident. However, if there is also cortical involvement the aphasia is likely to persist.

Question 23

Aphasic syndromes and their neuroanatomical findings, and possible associated features (Stucky pg 68)

Answer 23

Broca’s: Frontal operculum in the dominant hemi or posterior portion of the inferior frontal gyrus of the left hemisphere, including the third frontal convolution of the left hemi and subcortical white matter extending posteriorly to the inferior portion of the motor strip. Common right hemiparesis (arm more affected than leg), right facial droop.

Wernicke’s: Posterior superior portion of the left temporal lobe or the auditory association cortex adjacent to Heschl’s gyrus of the primary cortical auditory center. can see occasional superior quadrantanopia.

Conduction: Considered a disconnection syndrome because of damage to the arcuate fasciculus, thus disconnecting Broca’s from Wernicke’s area, but the syndrome can also occur with damage to the posterior superior aspect of the left temporal lobe, supramarginal gyrus, or deep parietal matter. Common hemisensory defect and cortical sensory loss.

Global: involves the entire perisylvian region in a typical MCA pattern but may be caused by two separate noncontiguous lesions affection Broca’s and Wernicke’s areas and excluding primary motor cortices. Common right hemiplegia and right hemisensory defect.

Anomic: No specific location for the pathology, but it often involves the angular gyrus in the dominant hemi and disconnection between W and intrasensory input areas in the parietal, temporal, and occipital lobes. Associated features are rare.

Transcortical Motor Aphasia: Usually anterior to B area, often in the supplementary motor area of the dominant hemi or in the frontal tissues between that region and teh dominant hemi operculum. Occasional right hemiparesis.

Transcortical sensory: Usually at the junction of parietal, temporal, and occipital regions in the angular gyrus in the dominant parietal region, sparing W area. Common hemisensory defect; uncommon right hemiparesis.

Transcortical mixed: essentially isolation or disconnection of the speech area; Involves the entire vascular borderzone area in both the frontal and parietal zones. Common right hemiparesis and hemisensory defect.

Alexia without agraphia: considered a disconnection syndrome isolating higher order visual systems from the language systems; involves the left occipital area and corresponding inferior portion of the left side of the splenium of the corpus callosum. Color onomea, trouble spelling and comprehending spelling, bilateral right visual field hemianopsia.
Alexia with agraphia: Involves lesions in the posterior margin of the parietal lobe (i.e., angular gyrus). common right hemiparesis and hemisensory defect.

word deafness: appears to involve damage to both temporal lobes with destruction of heschl’s gyrus on the left and the white matter tract connecting it to the auditory association area on the right. No specific associations

Question 24

Aprosodia:

Answer 24

Aprosodia:
-Disorders of prosody indicate that the non dominant hemisphere does contribute some important input to language in the form of para verbal communication. There are two types of a prosodia. The first is expressive a prosodia, characterized by an inability to properly convey the inflection and tonal quality of emotion, such that speech often has a robotic quality. The pathology here typically involves the area contralateral to broca’s area. The second is receptive aprosodia, characterized by difficulty interpreting emotional prosody, rhythm, pitch, stress, intonation, and so on and manifested in an inability to recognize sarcasm, cynicism, jokes, and other idiomatic forms of speech. The pathology is often due to dysfunction in regions contralateral to W area.

Question 25

Auditory agnosias

Answer 25

A form of agnosia that manifests in a disturbed capacity to recognize the nature of formerly familiar non verbal acoustic stimuli despite intact hearing and intact ability to recognize verbal stimuli (i.e., speech). specific localization for the pathology of auditory agnosia is uncertain beyond involvement of auditory cortex of the right temporal and or bilateral temporal lobes.
Auditory Agnosias
—Agnosia for sounds involves an inability to recognize the meaning of non verbal environmental sounds like the sound of a train or the bark of a dog. It is often associated with disorders of pure word deafness. These disorders are usually associated with bilateral lesions in the primary auditory cortex located within the temporal plane, especially the structures around heschl’s gyrus.
—Ignasia for music: also known as amusia, is an inability to recognize the meaning of musical sounds. Deficits can range from an inability to appreciate or understand rhythm to an inability to understand musical sounds as anything more than noise. This disorder is rare and is associated with lesions in the right or bilateral temporal lobes.

Question 26

The “specialized movement” visual stream

Answer 26

A third stream, which is often referred to as the superior temporal sulcus system has also been proposed. This system is also known as the specialized movement stream and involves the analysis of objects and body parts in motion.

Question 27

What and Where streams of Visual processing

Answer 27

“what Stream”: ventral pathway. Identifies the form of visual stimuli in terms of colors, objects, faces, and letters. Neuro anatomical findings: projects to occipital- temporal association cortex, connecting striate, pre striate, and inferior temporal regions. Associated disorders include visual agnosias. Examples of test measures: Hooper visual organization test, picture completion.

“where Stream”: Dorsal pathway. Processes spatial relationships, locating and analysis of objects in space. neuro anatomical findings colon projects to parietal-occipital association cortex, connecting straight, pre striate, and inferior parietal regions. Associated disorders include spatial analysis and processing impairments. Examples of test measures include judgment of line orientation and block design.

Question 28

Prosopognosia etiology:

Answer 28

Most often genetic or developmental, but can result from acquired brain injury typically involving bilateral lesions in ventral/inferior occipital-temporal areas (i.e., the fusiform gyrus). Viewed as an associative agnosia.

Question 29

Most often genetic or developmental, but can result from acquired brain injury typically involving bilateral lesions in ventral/inferior occipital-temporal areas (i.e., the fusiform gyrus). Viewed as an associative agnosia.

Answer 29

Location of objects in space: typically located in either unilateral or bilateral occipital parietal junction

Spatial analysis: typically located in the posterior right hemisphere

constructional apraxia: usually involves both frontal and parietal systems and may result from either left or right hemisphere damage, but is most likely to result from right parietal lesions and bilateral parietal lobe lesions.

Dressing apraxia: usually implies a lesion in the right parietal- occipital region.

Achromatopsia: can be both unilateral and bilateral, involving posterior medial regions and the calcarine cortex more on the left than the right.

Spatial acalculia: generally subsumed by the right parietal lobe.

Question 30

Spatial acalculia

Answer 30

although acalculia is not always spatially based, in some cases of this, the acquired deficit in calculation of ability results from spatial confusion, that is, difficulty processing the spatial aspects of written problems (e.g., confusing the columns within problems). this is most often associated with right hemisphere lesions.

Question 31

Memory

Answer 31

Refers to the complex process of encoding, retaining, and retrieving information. Learning is highly dependent on various aspects of attention in that information cannot be initially attained or encoded if the individual does not perceive or process. Memory and learning are critical drivers in the process of behavioral change. Like attention, memory is diffusely represented, subsumed/coordinated by various brain structures, and comprised of multiple types, as well as of various models, such as the information processing and multi storage models.

Question 32

Retrograde amnesia

Answer 32

This is amnesia for events prior to an accident, illness, or event; it is typically temporally graded, whereby events immediately before our last, whereas more remote memories remain intact.Ribot’s law States that the oldest memories are the most resistant to amnesia. Studies have underscored an association between severity of retrograde amnesia and extent of hippocampal pathology.

Question 33

Anterograde amnesia

Answer 33

This is an inability to learn or encode new information or form new memories. It is often referred to as in inability to form continuous memories.
—Post- traumatic amnesia (PTA) is a type of anterograde amnesia that typically results from acquired brain injury but can also occur during other conditions and acutely impact brain function (e.g., delirium). the length of PTA is one of the best indicators or predictors of TBI severity and long term outcome.

Question 34

functional amnesia

Answer 34

Aka psychogenic amnesia, including fugue. This is believed to have a psychiatric etiology, rather than one caused by physical injury. Anterograde amnesia is rare. Retrograde amnesia can include personal identity and or be limited to autobiographical memory. It is often triggered by an emotionally traumatic event.

Question 35

Infantile amnesia

Answer 35

This is failure to recall autobiographical information from early childhood years; Thought to be normal part of development.

Question 36

Information Processing Model of memory:

Answer 36

Encoding: active organization or manipulation of incoming stimuli, such as through rehearsal and repetition.
Storage:transfer of transient memory to where it can be made more permanent period
Consolidation: process by which encoded information undergoes a series of processes that render the memory representations progressively more stable and permanent.
Retrieval: the ability to access previously stored information; by way of cues. Tip of the tongue phenomenon

Question 37

3- stage model of memory

Answer 37

Sensory memory: holds information only one- 2 seconds for “iconic” (visual) and 3-4 seconds for “echoic” (auditory)
Short-term memory: Limited capacity of 7 +/- 2 items (Ebbinghaus); This store whereby information can be held for up to several minutes; Often equated with working memory and attention.
Long- term memory: a more permanent memory store where information is stored by way of consolidation or learning. It requires the hippocampus where structural change takes place due to long- term potentiation. Not as chronologically old as remote memory.
Remote memory: old memories, which are thought to be more stable or resilient to damage and disease than recent memory.

Question 38

Types of memory

Answer 38

Declarative memory (explicit): memory system concerned with the conscious retrieval or recognition of contextually related information or episodes.

Semantic memory: knowledge of facts; Not time dependent.

Episodic memory: knowledge of temporal events; Autobiographical

Prospective memory: remembering to do something at a particular time in the future. It is a process that also involves executive abilities and frontal systems. Declines with age.

Non- declarative memory (implicit or procedural): a memory system that is responsible for skills, procedures, habits, and classically conditioned responses and takes place largely without awareness.

Source memory: knowledge of where and when something was learned; related to episodic memory.

Metamemory: knowledge of one’s own memory.

Question 39

Types of memory interference

Answer 39

Retroactive interference: a process by which recently learned information interferes with the ability to remember previously learned information.
Proactive interference: a process by which previously learned information interferes with new or current learning.

Question 40

Transient global amnesia

Answer 40

Has an ideology usually due to hypo perfusion of medial temporal or dense italic areas, and resultant disconnection of lateral and medial limbic circuits. However, causes are often unclear and can include strategic infarction (e.g., perirhinal/parahippocampal cortex), migraine, and can also occur after electroconvulsive therapy period this is an acute- onset memory loss that typically lasts for less than 10 hours (but can last days) and results in profound and tarot grade amnesia and variable retrograde amnesia. The person usually remains alert and oriented to self. Confabulation is common.

Question 41

Anoxia/hypoxia

Answer 41

damage to the medial temporal lobe, particularly area CA one of the hippocampus (part of the medial limbic circuit), may result from an anoxic injury, with consequential memory loss. However, when the lateral limbic circuit is affected as well, memory loss is more severe with a consequence of dense amnesia (typically, a pronounced antero grade amnesia). In some cases, the amnesia is profound but in others memory performance improves with retrieval cues. Unlike other amnestic disorders, insight may be preserved and confabulation is not often present.

Question 42

Anterior communicating artery aneurysm

Answer 42

Rupture of an aneurysm of theACoA often results in basal forebrain, striatal, and frontal system damage, as well as disruption of cholinergic neurons that project to both medial and lateral limbic circuits. This, in turn, causes a frontal amnesia characterized by confabulation, attentional problems, disorientation, some apathy/lack of insight, sensitivity to proactive interference and variable retrograde amnesia.

Question 43

Wernicke- korsakoff syndrome

Answer 43

Occurs as a result of chronic alcohol use and thiamine deficiency. Korsakoff’s syndrome involves a diencephalic amnesia that results in both anterograde and retrograde amnesia (loss of remote memory), proactive interference, temporal order impairment, confabulation, and poor insight. It is also associated with gait ataxia, oculomotor palsy, and encephalopathy.

Question 44

Herpes encephalopathy

Answer 44

And infection caused by the herpes virus which preferentially affects the medial and inferior temporal lobes in the amygdala. Often, this initially results in amnesia, aphasia, and agnosia.

Question 45

Surgical ablation

Answer 45

Historically, extensive bilateral medial temporal resection for intractable epilepsy has resulted in veer antero grade amnesia, due to hippocampal/parahippocampal (medial circuit) as well as amygdala (lateral circuit) damaged. Unlike some of the other disorders listed here, many patients have preserved insight and are not prone to confabulation.

Question 46

Posterior cerebral artery stroke (memory findings)

Answer 46

The brain regions affected, and the resulting amnesia, depends on the laterality of the lesion; however, the pathology involves medial temporal and posterior occipital lobes. Associated cognitive deficits also include visual deficits, hemianopia alexia, color agnosia, and object agnosia.

Question 47

Brain systems, underlying structures, and disorders associated with memory

Answer 47

Hippocampal pathway or papez circuit

• entorhinal cortex
• fornix
• mammillary bodies
• mammillothalamic tract
• cingulate cortex
• –Hypoxia and anoxia

Amygdaloid Pathway

• amygdala
• dorsal medial thalamus
• dorsomedial cortex
• –Herpes encephalitis
• –PTSD

Diencephalon

• anterior nucleus of the thalamus
• dorsomedial nucleus of the thalamus
• fornix
• mammillary bodies
• –korsakoff’s
• –CVA

Basal Forebrain

• medial septal nucleus
• diagonal band of Broca
• Nucleus Basalis of Meynert
• –AD, ACoA aneurysm

Cortex

• medial and anterior temporal lobe
• frontal lobe (see basal forebrain)
• –surgical ablation, TBI, herpes, anoxia/hypoxia

Question 48

Cummings (1993) 3-syndrome model of Executive Function

Answer 48

Particular deficits result from damage to three discrete areas:

• Dorsolateral prefrontal syndrome (dysexecutive syndrome): characterized by poor problem solving, wordlist generation, organization, sequencing, abulia/amotivation (“pseudo depression”), and sometimes perseveration.
• orbitofrontal syndrome (inferior/ventral frontal syndrome): characterized by emotional ability, impulsivity, disinhibition, childishness, personality change, and distractibility.
• Medial frontal/cingulate syndrome: by decreased initiation and indifference, but can also have amnesia, incontinence, and leg weakness. Cummings also identified the motor circuit (supplementary motor area) and oculomotor circuit (frontal eye fields).

Question 49

Symptoms commonly associated with disorders involving executive systems

Answer 49

Motor sequencing: performing tasks in a specific order. Usually caused by damage to prefrontal and/or dorsolateral prefrontal area

poor directed attention: ability to allocate and direct attention. Pre frontal, frontal eye fields

Poor working memory: information that is actively maintained or rehearsed, that can be retained for up to several minutes. Dorsolateral prefrontal area

Perseveration: uncontrolled repetition of a response. Dorsolateral prefrontal area

Failure to maintain response set: inability to maintain a task after it has been acquired; Do to distract ability. Prefrontal

Poor reasoning:abstract reasoning, judgment. Dorsolateral prefrontal area.

Abulia: lacking in initiation/motivation/concern. Dorsal lateral prefrontal area, also basil ganglia and anterior cingulate (medial frontal)

Poor planning/organization: inefficient planning and/or organization (involves prioritizing and goal setting). dorsal lateral prefrontal area, orbitofrontal area

impulsivity: acting on impulse, without thought. Orbitofrontal area

emotional lability: inability to control emotions. Orbitofrontal area

utilization behavior/environmental dependency (stimulus-bound behavior): when patients tend to respond to whatever stimuli are at hand, even when inappropriate. Orbitofrontal, mesial frontal, anterior cingulate.

Witzelsucht: Inappropriate jocularity. Orbitofrontal area

disinhibition: inability to inhibit, or control, a response or behavior, regardless of its inappropriateness. Orbitofrontal area, anterior singulate

apathy/akinetic mutism. Inability to speak or move. anterior cingulate

depression: the left frontal lobe is thought to underlie positive emotional valence so that, with injury depression results. Left frontal

reduplicative paramnesia: feeling that a place has been duplicated. Right posterior parietal, frontal

Capgras syndrome: feeling that a person has been duplicated or is an impostor. Right temporal, bilateral frontal

Anosognosia: unawareness of deficit; Different than denial in that there is often limited defensiveness and the lack of awareness is not related to psychological denial or avoidance. May result from diffuse brain injury and focal damage to frontal, posterior parietal, and right hemisphere regions

Question 50

Executive dysfunction in children with prader willi syndrome

Answer 50

these children may exhibit hyperphagia and obesity, secondary to hyperactivation in limbic reward circuitry (amygdala closed parentheses and hypo activation and cortical inhibitory regions.

Question 51

Impulse control disorders in Parkinson’s disease

Answer 51

impulse control disorders, such as binge eating, pathological gambling, etc, have been observed in approximately 40% of Parkinson’s patients undergoing dopaminergic treatment, resulting in impaired fronto- striatal (sub-thalamic nucleus) and cingulo-frontal Connections associated with compulsive repetition.

Question 52

Finger agnosia

Answer 52

refers to loss of the ability to name or identify the fingers of one’s own hand(s) or the fingers of the hand of another person. Disordered finger recognition, along with a cow culea, right- left disorientation, and agraphia comprised the four parts of gerstmann syndrome. Finger agnosia is a special case of autotopagnosia, wherein 1 loses the ability to identify the parts of one’s body to command or imitation.
Can result from a lesion In the left inferior parietal lobe, in particular, the angular gyrus.

Question 53

Right-left disorientation

Answer 53

Involves an inability or loss of the ability to identify the right and left sides of one’s own body and the right and left sides of the body of another person. Like finger agnosia, right left disorientation is a special case of autotopagnosia, wherein when loses the ability to identify the parts of one’s body to command or imitation.
Can result from a lesion of the left inferior parietal lobe, especially the angular gyrus

Question 54

Somatagnosia

Answer 54

Somatagnosias Refer to disturbances in the general feeling pertaining to the existence of one’s body or recognition of one’s body schema. Disorders here typically result from parietal lobe system dysfunction.

• Asterognosia: Involves loss or acquired impairment in one’s ability to recognize the nature of an object by tactile mobility or other physical features, such as size and shape. Neuroanatomical: Usually unilateral and typically Associated with lesions of the posterior parietal region and rolandic gyri.
• Asomatognosia: An acquired disturbance in the knowledge or sense of one’s own body and bodily condition can be seen as a result of lesions in the bilateral parietal lobes, a unilateral lesion in the right inferior parietal region bordering the inter parietal sulcus, the supramarginal gyrus, and the angular gyrus, or a unilateral lesion involving the dominant parietal lobe, especially in the region of the angular gyrus.

Question 55

Apraxia

Answer 55

Apraxia is an impairment of the ability to carry out previously learned purposeful, skilled movements despite normal primary motor skills and normal comprehension of the act to be performed. Apraxia:
-cannot be explained by weakness, in coordination, sensory loss, impaired concentration, inattention, or intellectual impairment
-can appear as an isolated disorder, but its common association with aphasic syndromes makes it difficult to differentiate from impaired comprehension
-can manifest in relation to focal lesions, progressive dementing disorders, and stroke
-is frequently associated with anosognosia, so patients may be unaware of their apraxic deficits, and patients with apraxia often have right hemiparesis, so they may mistake their apraxia deficits with difficulty moving the affected limb.
Examination for a praxilla should include pantomime of object use and tests designed to evaluate transitive movements (i.e., those done as a goal directed movement with an object) and intransitive movements (i.e., those done without a specific goal and without use of an object, like hand gestures), as well as the ability to carry out serial acts (e.g., pretending to prepare a cup of tea or light a pipe).

Disorders of apraxia are frequently associated with lesions in or near the language zone of the left hemisphere, but can be the result of bilateral lesions. Localizes generally to the left inferior parietal lobule (sensory area), and frontal lobe systems, particularly the premotor cortex, supplementary motor area, and frontal convexity, and- as a result of disconnection- the corpus callosum.

Question 56

Apraxia of speech

Answer 56

not specific to one anatomical location. Apraxia of speech is not a language disorder but involves impairment and planning the movements necessary for speech production. Both the acquired version and the childhood version can be manifest in inconsistent articulation errors and difficulty with correct articulatory placement. A praxilla of speech is a disorder of the planning and organization of articulatory movement, in contrast to dysarthria, which is a disorder of motor coordination. In the childhood version, a defining characteristic is often the child’s ability to pronounce single words or words in series (e.g., ABCs, numbers) but in conversation/volitional speech dysprosodic rhythm and poor articulation are apparent.

Question 57

Buccofacial apraxia

Answer 57

involves difficulty performing voluntary skilled motor movements of the face, tongue, lips, and cheeks on command. Measures to assess intransitive buccofacial gestures might include puffing out the cheeks and sticking out the tongue; Measures to assess transitive buccofacial gestures might include pretending to suck on a straw or sniff of flower.

Question 58

Gait apraxia

Answer 58

refers to a loss of the normal capacity to use the legs appropriately for the act of walking, in spite of the ability to demonstrate correctly the use of the legs for the act of walking when lying flat.

Question 59

Ideational apraxia

Answer 59

has been associated with bilateral, non focal lesions and with left hemisphere lesions, especially the posterior temporal- parietal junction. This is a loss of the ability to plan and execute complex gestures, as though one has lost the idea behind the gesture or use of a tool even though knowledge about the use of the tool is unaffected. It involves problems in motor planning and is manifest in errors and sequencing the necessary actions for a task (e.g., lighting a pipe before putting in the tobacco). Assessment of serial acts is important in identifying this disorder.

Question 60

Ideomotor apraxia

Answer 60

usually involves lesions in the left inferior parietal lobe or supplementary motor area or a lesion in the corpus callosum. Refers two loss of the ability to perform or pantomine transitive or intransitive gestures on command and to imitate, although spontaneous production of the gesture may remain intact. It involves difficulty making believe one is using a tool and is manifest in tool used and gestures. During pantomime, patients with video motor apraxia will often use a body part as if it were an object. Measures to assess and transitive limb gestures might include waving or saluting, whereas those that assess transitive limb gestures might include pretending to use a comb or scissors.

Question 61

Limb- kinetic apraxia

Answer 61

unlike other apraxia disorders, appears to be the result of lesions in the pyramidal motor system. This involves an inability to precisely move one’s hands or legs, but is not viewed as related to skilled movement because there is no apparent inability to select or sequence motor movements, and it is present with pantomime, imitation, and the use of objects. It affects goal- directed transitive movements more than simple intransitive gestures, is more often asymmetric than symmetric, and effects distal more than proximal movement.

Question 62

Anosodiaphoria

Answer 62

Order wherein patients are aware that they have impairments (e.g., paralysis), yet show no emotional concern or distress about it; Neglect also often present period this is in contrast to La Belle indifference, which is lack of concern for symptoms/disability secondary to conversion disorder. Scene in damage to the right parietal or frontal systems.

Question 63

Alexithymia

Answer 63

an inability to understand, process, or describe one’s own emotions. seen in damage to the right hemisphere, particularly amygdala; also insula, anterior cingulate, and fusiform gyrus.

Question 64

Emotional ability

Answer 64

Fluctuations of emotion and/or increased emotional reactivity. Seen in damage to the orbitofrontal area or limbic system

Question 65

rumination

Answer 65

Deadly going over a thought or problem in an unproductive way. Seen in damage to the subgenual prefrontal cortex.

Question 66

Pseudobulbar affect

Answer 66

type of emotional lability; Extreme involuntary emotional responses (i.e., tearful crying, excessive laughing) to mild stimulation. Due to pseudobulbar palsy, or damage to the upper motor neuron corticobulbar tract and connections to the cerebellum.

Question 67

Dysphonia

Answer 67

Disorder involving difficulty in vocalization.

Question 68

Literal paraphasias

Answer 68

Phonemic paraphasias. The substitution or the rearrangement of sounds or syllables in otherwise correct words, for example fig instead of pig

Question 69

phonology

Answer 69

The underlying speech sounds in a language and the rules governing the production of speech sounds.

Question 70

Pragmatics

Answer 70

the context in which the words are used

Question 71

syntax

Answer 71

the rules governing the structure of phrases and sentences

Question 72

verbal paraphasias

Answer 72

the substitution of 1 correct word for another period some substitutions may have no obvious semantic relationship with the correct word, while others involve substitution of a correct word or phrase for another semantically related word or phrase. Sometimes paraphasias take the form of neologisms (zoctor for doctor).

Question 73

Fetal alcohol spectrum disorder (FASD)

Answer 73

alcohol (ethanol) is a teratogen that passes through the placental barrier and affects the developing fetus throughout gestation. Intrauterine alcohol exposure results in a heterogeneous pattern of neurological, cognitive, behavioral, and physical symptoms that have been defined differently acrossing a variety of classification systems. FASD is an umbrella term, not a diagnostic term, that describes the craniofacial, cardiovascular, skeletal, and neurological deficits that can occur when alcohol is consumed during pregnancy.

Medical disorders that collectively comprise FASD include Fetal alcohol syndrome, and partial FAS, alcohol-related birth defects, and alcohol-related neurodevelopmental disorder.

New DSM-5 now includes the diagnosis, Neurobehavioral Disorder Associated with Prenatal Alcohol Exposure.

FASD are the leading cause of preventable intellectual disability (ID), birth defects (i.e., heart, kidney, and bone problems and other malformations; difficulty seeing and hearing; and reduced immune function) and developmental disorders in the Western hemisphere and result in a substantial burden of cost. Consensus at this time is that no level of alcohol consumption during pregnancy is considered safe.

Question 74

Neuropathology of prenatal alcohol exposure

Answer 74

leads to alterations in size and structure across brain regions. During the 1st and 2nd trimester, prenatal alcohol consumption interferes with the migration, proliferation, and organization of brain cells, resulting in varying craniofacial and brain malformations. During the 3rd trimester, consumption is associated with damage to the cerebellum, hippocampus, and prefrontal cortex. Neurochemical effects of alcohol may include:

• increased turnover of norepinephrine and dopamine
• decreased transmission in acetylcholine systems
• increased transmission in gamma-aminobutyric acid (GABA) systems
• Increased production of beta-endorphin in the hypothalamus

Neuroimaging studies reveal that white matter may be disproportionately impacted in FASD. Additional structural brain abnormalities associated with FASD include, but are not limited to, the following:

• microcephaly
• migrational anomalies (e.g., heterotopias)
• disproportionate reduction in gray and white matter volumes, particularly in frontal, parietal, and temporal lobes
• white matter hypoplasia > gray matter hypoplasia

Question 75

Institute of Medicine Diagnostic Classification for Fetal Alcohol Spectrum Disorder (FASD)

Answer 75

Fetal Alcohol Syndrome with confirmed maternal alcohol exposure
A. Confirmed maternal alcohol exposure
B. evidence of a characteristic pattern of facial anomolies that include features such as short palpebral fissures and abnormalities in the premaxillary zone (e.g., flat upper lip, flattened philtrum, and flat midface).
C. Evidence of growth retardation
D. Evidence of CNS abnormalities such as structural brain abnormalities or neurologic hard or soft signs

FAS without confirmed maternal alcohol exposure: B, C, & D above

partial FAS with confirmed maternal alcohol exposure
A. confirmed maternal alcohol exposure
B. evidence of some components of the pattern of characteristic facial anomalies, as well as either C or D or E:
C. Evidence of growth retardation
D. Evidence of CNS abnormalities such as structural brain abnormalities or neurologic hard or soft signs
E. Evidence of a pattern of behavior or cognitive abnormalities that are inconsistent with developmental level and cannot be explained by familial background or environment alone (e.g., learning difficulties, poor impulse control).

Question 76

Diagnosis of Fetal Alcohol Syndrome

Answer 76

There are multiple classification systems due to the heterogeneity of clinical presentation, however, the following 4 criteria must be met for a medical FAS diagnosis:
1. Growth deficiency: defined as below average height and/or weight. Babies with FAS are often small for gestational age and may continue to show growth deficiency as adolescents and adults.

2. Craniofacial features: Specific pattern of facial anomalies that include short palpebral fissures (eye width decreases with increased prenatal alcohol exposure), a flat midface, a short upturned nose, a smooth or long philtrum (the ridges running between the nose and the lip), and a thin vermilion (the upper lip thins with increased prenatal alcohol exposure).
3. CNS dysfunction: CNS damage can be assessed structurally, neurologically, and functionally:
   - –Structural abnormalities: includes microcephaly of 2+ standard deviations below the mean, callosal agenesis, or cerebral hypoplasia
   - –hard neurologic signs: May include seizure disorders or another diagnosable disability. Soft neurological signs, which require more clinical judgment, may also be apparent, including fine or gross motor problems and hearing loss.
   - –Functional abnormalities: includes general cognitive deficits, deficits in memory, executive functions, attentional deficits, and learning disabilities.
4. Prenatal Alcohol Exposure: Confirmed or unknown prenatal alcohol exposure. Women often have difficulty accurately recalling the frequency or amount of alcohol consumption during pregnancy. At present, no biochemical marker can reliably confirm maternal alcohol consumption in pregnancy; however, studies are investigating the utility of fatty acid ethyl esters in meconium as markers for prenatal exposure.

Question 77

Institute of Medicine Diagnostic Classifications for Alcohol-Related Effects

Answer 77

Alcohol-related effects: clinical conditions in which there is a history of maternal alcohol exposure, and where clinical or animal research has linked maternal alcohol ingestion to an observed outcome. There are two categories which may co-occur. If both diagnoses are present, then both diagnoses should be rendered.

Alcohol-Related Birth Defects (ARBD)

Cardiac: atrial septal defects, ventricular septal defects, aberrant great vessels, tetralogy of Fallot

Skeletal: hypoplastic nails, clinodactyly, shortened fifth digits, pectus excavatum and carinatum, radioulnar synostosis, klippel-feil syndrome, flexion contractures, hemivertebrae, scoliosis, camptodactyly

Renal
aplastic, dysplastic, hypoplastic kidneys; horseshoe kidneys; ureteral duplications; hydronephrosis

Ocular
strabismus; retinal vascular abnormalities; refractive problems secondary to small globes

Auditory
conductive hearing loss; neurosensory hearing loss

Alcohol-Related Neurodevelopmental Disorder (ARND)
Presence of A or B or Both
A. Evidence of CNS abnormalities such as structural brain abnormalities or neurologic hard or soft signs
B. Evidence of a pattern of behavior or cognitive abnormalities that are inconsistent with developmental level and cannot be explained by familial background or environment alone (e.g., learning difficulties, poor impulse control).

Question 78

DSM-5 Criteria for Neurodevelopmental Disorder Associated with Prenatal Alcohol Exposure (ND-PAE)

Answer 78

listed as a diagnosis under Other Specified Neurodevelopmental Disorder. To meet criteria for a psychiatric diagnosis of ND-PAE, an individual must have been exposed to alcohol at some point during gestation, and that the exposure was more than “minimal,” although that determination is left up to clinical judgment. In addition, an individual must also display impaired neurocognitive functioning, self-regulation, and adaptive functioning.

Question 79

Fetal Alcohol Spectrum Disorders Epidemiology

Answer 79

incidence rates of FAS vary widely across countries due to different screening measures and underidentification or misdiagnosis. Recent data estimate the global prevalence of FAS to be 10%. General incidence is more than 2x higher in the US compared to Europe and other countries. The rate of FASD in the US is as high as 9.1 per 1,000 live births. In Europe, major factor associated with FAS is low SES rather than racial background, whereas in US, race and SES are often confounded. In the US, FAS is associated with higher maternal age and lower education level, diverse racial, educational, and economic backgrounds, untreated or undertreated mental health issues, social isolation, and a history of abuse. African American and Native American populations, which are typically characterized by lower SES, have incidence rates approximately 10 times higher (2.29 per 1,000) than those of middles and upper SES and Caucasian backgrounds (.26 per 1000). The rate of FASD is reported to be as high as 9.1 per 1000 live births in the US, comparable with or higher than rates for other developmental disabilities such as Down syndrome or spina bifida.

Question 80

Fetal Alcohol Spectrum Disorders Determinants of Severity

Answer 80

• Quantity (dose) consumed: Diagnostic criteria developed at the University of Washington state:
• -High Risk: a blood alcohol concentration greater than 100 mg/dL delivered at least weekly in early pregnancy (roughly equivalent to 55kg/121 lb woman drinking 6-8 beers in one sitting).
• -Some risk: the confirmed use of alcohol during pregnancy with use less than high risk or unknow usage patterns.
• -Unknown risk: The unknown use of alcohol during pregnancy
• -No Risk: the confirmed absence of prenatal alcohol exposure, which rules out a diagnosis of FAS.
• Pattern of Exposure: Chronic consumption (4-5 drinks daily) and binge drinking, which equates to 5+ standard drinks (12 oz beer, 5 oz wine, 1.5 spirits) in one sitting or more than 9 drinks per week, are associated with FAS. Lesser quantities consumed during pregnancy are associated with ARDB and ARND.
• Timing of Exposure: First trimester drinking increases the likelihood of FASD 12x; drinking during the first and second trimester increases likelihood 61x; and drinking in all 3 by 65x
• Additional Risk factors:
• polydrug use and their synergistic interactions
• higher maternal age
• maternal mental health issues
• lower education level
• reduced access to prenatal and postnatal care and services
• inadequate nutrition
• an environment that includes stress, abuse, and/or neglect

Question 81

FASD Presentation, Disease Course, and Recovery

Answer 81

Children with FAS have CNS damage that leads to lifelong neurocognitive and behavioral problems. Adolescents and adults with FAS face:

• school failure/greater likelihood to drop out of HS
• inability to secure and hold employment
• mental health issues
• delinquency; involvement with the law

Question 82

FASD Neuropsychological Assessment Expectations

Answer 82

Intelligence/Achievement: Greater variability in intellectual performance: IQ scores range from 20-120, with average between 65-72. Children with more dysmorphic features tend to have lower IQ scores. 25% with FAS and 10% with ARND have IQ scores of 70 or below. Even if a child with FASD does not have an ID, the child often has learning problems that interfere with sound judgment and can cause behavioral problems that significantly impact life. Some studies report greater impairment in verbal than nonverbal abilities, but findings are not consistent. Learning difficulties, lower overall school performance, disrupted school attendance, lower performance in reading and spelling, and deficits in mathematical skills have been reported.

Attn/concentration: large proportion (60-95%) with FASDs qualify for dx of ADHD; the disorder is 3-9x higher in children with FASD than in the general population. Pervasive deficits in visual sustained attention have been found. Deficits in auditory visual attention are task dependent and occur when intertarget intervals are long.

PS: Deficits in reaction time and cognitive efficiency have been found when tasks are more challenging and require complex cognition and the use of working memory

Speech and Language: Secondary to craniofacial abnormalities, some have reported problems with oral-motor function and speech production. Deficits in confrontation naming have been reported, as well as expressive and receptive language disorders. Problems with comprehension of higher level language, such as metaphors, sarcasm, and idioms, as well as deficits in pragmatic language and social discourse, have been documented.

VS: deficits in local versus global analysis of hierarchical visual stimuli have been documented. Deficits in VS construction (copying task) have been reported, although reduced performance is thought to be associated with motor deficits.

Memory: Verbal learning and mem deficits have been documented in children exposed to alcohol secondary to dysfunction in hippocampal dendrites; retention is intact when an implicit strategy is used. Deficits in memorizing verbal and nonverbal information result from difficulties with the acquisition of the info rather than the ability to remember the information over time. Studies examining visual memory are inconsistent in their findings. Some show impaired spatial recall, others show sparing of spatial retention and object recall.

EF: Deficits have been documented across many EF domains, including verbal and nonverbal fluency, response inhibition, planning and organizing, cognitive flexibility, and concept formation.

Sensorimotor function: Delayed motor development and fine motor deficits associated with reduced cerebellar size have been reported including tremors, weak grasp, and poor eye-hand coordiantion. Balance is particularly affected secondary to cerebellar involvement, but performance varies across task demands. Sensory integration problems, tactile defensiveness, and reduced or undersensitivity to stimulation have been reported.

Emotion and Personality: often classified as restless, impulsive, inattentive, disruptive, aggressive, or delinquent. Some children display socially disinhibited behavior, such as boundary issues, social intrusiveness, and lack of awareness of social dangers. Elevated levels of both internalizing and externalizing behavior disorders have been documented. Lack of social judgement, deficits in moral development, and failure to learn and generalize from experience contribute to problems with socialization. In later childhood and young adulthood, they are more likely to engage in antisocial behaviors and juvenile delinquency. There is significantly more sleep disturbance, shortened sleep duration and an increased rate of night awakenings, which interfere with school performance, learning, memory, academic performance, mood and behavior. Deficits in adaptive behavior exist across communication, socialization, and daily living skills domains.

Question 83

FASD Treatment Considerations

Answer 83

Early diagnosis is key (only 11% diagnosed by age 6 in one study). allows for services, intervention, to help reduce comorbid secondary diagnoses and improve overall outcomes and adaptation.

Important protective factors are early diagnosis, services from government developmental disability programs, living in a stable home, protection from violence.

Question 84

Neuropathology of cocaine use in utero

Answer 84

cocaine is a crystalline alkaloid derived from leaves of the coca plant. In utero exposure occurs primarily through maternal use of crack cocaine.

In utero exposure affects the CNS via its effects on the monoamine system, especially dopamine. Exposure early in gestation affects neural proliferation and migration, whereas exposure during later gestational stages may affect neuronal maturation and synaptogenesis. In utero exposure to cocaine may lead to abnormalities in the frontocingulate cortex, including the anterior cingulate gyrus.

Question 85

Cocaine in utero: epidemiology

Answer 85

In the US, prenatal exposure to cocaine occurs in 30,000-160,000 infants annually . Approximately .5 to 3% of pregnant women worldwide are estimated to use cocaine. Infants prenatally exposed to cocaine are often born with small head circumference and low birth weight.

Question 86

Determinants of severity of deficits in cocaine exposure in utero

Answer 86

Dose-response relationship between amount of in utero exposure and later neurobehavioral problems.

Question 87

Cocaine in utero: presentation, disease course, and recovery

Answer 87

infants exposed to cocaine in utero often display many neurobehavioral characteristics during the neuonatal period including poor sleep cycles, abnormal startle response, abnormal brainstem evoked potentials, and other evidence of immature neurological functioning. Toddler/preschoolers wo were exposed prenatally often show impulsivity and emotional lability in response to frustration.

Question 88

Cocaine in Utero: Expectations for Neuropsychological Assessment Results

Answer 88

Intelligence/Achievement: Studies have documented lower overall IQ. Deficits in academic achievement may be more related to environmental variables, such as parent education and SES

Attn/Concentration: Deficits in sustained and selected attention are the most consistently documented neuropsyc deficits.

PS: Slower reaction times have been documented on continuous performance tasks , although this may be a function of poor attention regulation.

Language: language delay has been seen, with expressive language being most affected.

VS: Deficits in visual perceptual organization are common.

Memory: Primary deficits in working memory are consistently documented.

EF: Perseveration, disinhibition, and poor task orientation have been found

Emotion and personality: often impulsive and display poor emotional control. Emotional/behavioral problems are more likely to be seen in frustrating or novel contexts.

Question 89

Cannabis in Utero: Definition and Neuropathology

Answer 89

cannabis is most commonly used illicit drug. It is derived from the Cannabis plant and is used for its psychoactive and medicinal properties (e.g., it is used for the stimulation of hunger, pain relief, and reduction of nausea and vomiting). Cannabis preparations are largely derived from the female plant of the Cannabis sativa, and consists of approximately 60 plant-derived cannabinoid compounds (phytocannabinoids), wtih THC being the predominant psychoactive constituent. The cannabinoid receptor type 1 (CB1) is the primary target in the brain for THC, and the rewarding property of cannabis has been associated with the mesocorticolimbic dopamine system. Delta-9 THC, the main psychoactive compound, produces changes in mood, perception, motor coordination, short-term and working memory, and concentration. THC readily crosses the placenta during gestation. THC is secreted in maternal milk during lactation at estimates of up to eightfold higher concentrations in breast milk than in maternal plasma concentrations.

The endocannabinoid system exists from the earliest stage of pregnancy, in the preimplantation embryo and uterus, placenta, and in the developing fetal brain, presenting multiple points of vulnerability throughout gestation. Prenatal cannabis exposure (PCE) has been found to be associated with fetal growth restriction in mid and late pregnancy, and also with lower birthweight. Continued PCE affects dopamine signaling within and beyond the mesolimbic system.

Infants exposed to cannabis in utero have not been found to be at increased risk of birth defects, but an increased risk of stillbirth among women who used in pregnancy has been demonstrated. Altered sleep patterns have been found, with these infants displaying increased irritability, excitability and arousal 24-72 hours after birth. Heavy exposure is reported to cause delay in infant visual maturation and visual attentiveness. The most consistent and visible consequence of regular heavy use is significantly heightened tremors, exaggerated startle and visual responses, and poor habituation to novel stimuli, which is thought to reflect nervous system immaturity and/or drug withdrawal. Other motor differences observed among the infants of heavy users include an exaggerated Moro reflex, increased occurrence of athetoid movements, and disinhibition in a number of motor tests, which are behaviors similar to those observed in infants undergoing narcotic withdrawal.

Question 90

Cannabis in Utero: Expectations for Neuropsychological assessment results

Answer 90

-Intelligence/Achievement: Prenatal exposure does not appear to affect overall IQ, but it has been associated with underachievement in reading and spelling. Lower scores occur in reading, math and spelling, most notably in those exposed to heavy marijuana use in the first trimester when home environment, race/ethnicity, SES, and other prenatal substance use were controlled for.

Attn/Concentration: problems with attention and concentration are seen; however, prenatal alcohol exposure is usually a confounding factor in this research. ONe study showed that of children exposed prenatally, the first- and third-trimester exposures predicted increased hyperactivity, inattention, and impulsivity in later childhood and adolescence.

EF: deficits evident in top-down processing, including working memory, focused attention, behavioral inhibition, self-regulation and monitoring, and cognitive flexibility.

VS: A neuroimaging study has shown altered neural functioning during VS working memory processing after controlling for other prenatal and current drug use. One study showed prenatal exposure predicted visual memory, analysis, and integration deficiencies. Problems with abstract and visual reasoning, and visual-perceptual functioning have also been documented.

Sensorimotor functions: decreased rates of visual habituation and increased tremors in 4-day-old infants. By 1 yo, however, no adverse behavioral effects of prenatal exposure were noted.

Emotion and Personality: one study showed in heavy users, kids were significantly more likely to report delinquent behavior in middle adolescence, after controlling for maternal substance use, household income, home environment, maternal IQ, and child’s race. PCE is a contributory factor for increased vulnerability to neuropsychiatric disorders (e.g., schizophrenia). There is an increased rate of mood (i.e., depressive symptoms) and behavior dysregulation (impulsivity and hyperactivity) and delinquent behavior in children with PCE.

Question 91

Mercury Exposure: Definition and Neuropathology and Neuropsychological Findings

Answer 91

Mercury (Hg) is a natural element that exists in the environment in metallic, inorganic, and organic forms. The most common compound, methylmercury, is formed in water and soil by microscopic organisms. Mercury is widely used in industry, agriculture, and healthcare. Common sources of mercury include fungicides and pesticides (most contain methylmercury), cosmetics, dental fillings, commercial thermometers, and high-efficiency compact fluorescent bulbs (CFL). Coal-fired power plants, which release mercury into the air when coal is burned, are the largest man-made sources of mercury. Airborne mercury makes its way into water sources and bioaccumulates in fish. Eating fish contaminated with methylmercury is the primary human exposure. The highest concentrations occur in predatory species (e.g., shark, tuna, swordfish) and shellfish.

Neuropathology: Mercury in its many forms can be ingested, inhaled, or absorbed through the skin. Neurologic, gastrointestinal, and renal systems are the most commonly affected organ systems in mercury exposure. When handled, elemental mercury (e.g., silvery liquid found in barometers) is absorbed very slowly through the skin; mercury vapor is absorbed about 50 times faster through the lungs. Methylmercury, an organic mercury compound, binds to proteins and compounds and gains access to brain tissues by active transport into the endothelial cells in the BBB. Methylmercury destroys neurons and causes cerebral atrophy in both hemispheres. Dimethylmercury is the deadliest of the mercury compounds. It easily permeates the skin, gets into the bloodstream, and is deposited in the brain, kidneys, and other organs, resulting in acute mercury poisoning. Symptoms begin with paresthesia, deterioration in fine motor coordination, and restriction of the visual fields, and then progresses to severe ataxia, dementia, and death.

Pre- and postnatal exposure: pregnant women with a diet high in fish and shellfish are at greatest risk of methylmercury exposure. Because it is lipophilic (Fat soluble), methylmercury crosses the placental barrier and the BBB and is poorly excreted by the fetus, allowing accumulation in the CNS. Neuropathology in fetal cases is more widespread than in children or adults and can result in atrophy and hypoplasia of the cerebral cortex and corpus callosum, abnormal cytoarchitecture, and dysmyelination of the pyramidal tract. Mercury’s harmful effects to the fetus include brain damage, ID, poor motor coordination, blindness, seizures, and inability to speak. Infants and children may also be exposed postnatally to mercury through breast milk.

Determinants of severity: A linear dose-response relationship exists. fetuses have greater risk bc of their inability to excrete mercury.

Presentation, disease course, and recovery: all forms of Mercury are toxic to the fetus, but methylmercury most readily passes through the placenta. Offspring of women exposed to significant mercury have progressive cortical degenerative disease, cerebral palsy, ID, severe sensory deficits, microencephaly, and limb malformations (now coined congenital minamata disease). Neuropathology indicates the occipital cortex and cerebellum are most affected.

Mercury exposure: Neuropsychological findings

• Seychelles prospective cohort study: Methylmercury levels were unrelated to any neurodevelopmental parameters; However, activity levels and boys decreased as maternal hair methylmercury concentrations increased.
• Faroe Islands Prospective Study: Higher cord blood methylmercury levels were associated with deficits and motor skills, attention, language, visuospatial skills, and memory.
• New Zealand Study: Higher prenatal exposure (>6 ppm in maternal hair samples) we’re significantly associated with expressive language and visual spatial deficits and lower overall intelligence scores.

Question 92

Mercury Exposure: Epidemiology

Answer 92

blood level is measured in micrograms of mercury per deciliter of blood. The US EPA’s reference dose for methylmercury is .1 per kg body weight per day. Mercury levels in women of childbearing age dropped 34% from a survey conducted in 1999 to 2000 to follow-up surveys conducted from 2001 to 2010. Additionally, the percentage of women of childbearing age with blood mercury levels above the level of concern decreased 65% between the 1999-2000 survey and the follow-up.

-More than 300,000 newborns each year are estimated to be at increased risk of learning disabilities associated with in utero exposure to methymercury.

Question 93

Common exposures to Mercury

Answer 93

• -Consumption of Fish and Shellfish
• the US FDA recommends that pregnant women, breastfeeding mothers, and young children avoid eating fish with a high mercury content, such as shark, swordfish, tilefish, and king mackerel and fresh, frozen, and canned albacore tuna. However, recent studies have not shown any deleterious associations between intellectual functioning and behavior and the consumption of recommended service sizes of various types of fish during pregnancy. In fact, several have demonstrated protective association for fish consumption (.2 servings/week), particularly with respect to ADHD-related impulsivity and hyperactivity.
• –Vaccines
• Thimerosal (~50% methylmercury) was used as a preservative in pertussis, diphtheria, tetanus, and influenza vaccines. In 2000, the US public health service ordered the removal of this from all vaccines. No good empirical evidence has linked vaccines containing this ingredient with autism spectrum disorders or other neurodevelopmental problems.
• –Dental amalgams
• The Public health service concluded that dental amalgams do not pose a serious health risk of mercury poisoning so are not a likely source of in utero exposure.

Question 94

Polychlorinated biphenyls (PCBs): Definition and Neuropathology

Answer 94

PCBs are part of the family of man-made organic chemicals known as chlorinated hydrocarbons. Prior to 1979, PCBs were commonly used in Transformers, adhesives and tapes, plastic and rubber products, oil based paint, electrical devices and appliances, and carbonless copy paper. The primary human exposure occurs through the food chain, via highly contaminated fish and sea mammals.

Neuropathology: The principal root of prenatal exposure is maternal consumption of seafood before and during pregnancy. The PCBs Are noted to be endocrine disruptors. Polychlorinated biphenyls exposures have been associated with changes in thyroid hormone levels in infants and decreased size of the splenium of the corpus callosum.

Epidemiology: Large scale studies conducted in Oswego, New York, Michigan, the Netherlands, and Germany show similar impact of PCB’s on neuro development.

Determinants of severity: dose dependent associations exist between PCB level and neurobehavioral impairment. The neurotoxic effects of PCB’s on dopamine activity are potentiated by methylmercury.

Presentation, Disease Course, and Severity: Asian studies showed that exposure in utero was associated with low birth weight and delays in sensory motor and cognitive abilities. Limited studies suggest that the general profile of neurocognitive performance after enduro exposure to PCB’s shows reduced verbal abilities and deficits and executive functions.

Question 95

Inorganic lead (Pb): Definitions and Neuropathology

Answer 95

inorganic lead is a common environmental metal that is a known neurotoxin. Sources of exposure in humans include drinking water from lead pipes, as well as imported candies, toys, cosmetics, and pottery. In the United states, blood was banned in paint and gasoline in the 1970s; However, pregnant mothers, infants, and children can still be exposed to lead via paint chips and paint dust during renovations. Currently, in utero exposure to lead is most likely to occur from maternal occupational exposure.

Neuropathology: inorganic lead can mimic calcium and thus pass through the blood brain barrier. Once in the CNS, lead interferes with neurulation, migration, synaptogenesis, and neurotransmission. in the fetus, lead crosses the placenta and accumulates in fetal organs. Animal studies have suggested that lead may specifically affect the dopamine system. Imaging studies in children exposed to lead have been equivocal. MRI studies have documented decreased cerebral volume in the frontal greymatter, anterior cingulate, and prefrontal cortex. MRRS studies have documented decrease in the N-acetylaspartate-to-creatinine ratio, which is a possible indicator of neuronal loss.

Epidemiology: approximately 250,000 US children aged one to five years have blood lead levels that are above the action level recommended by the CDC. Incidence rates have declined sharply in recent years but remain high in low income areas, minority children, and children living in older homes. Unborn children and young children are at greatest risk for poor health and neurobehavioural outcomes from lead exposure.

Determinants of severity: blood lead levels are measured in micrograms of lead per deciliter of blood. The United states Centers for Disease control and prevention (CDC) determines the current action level or level at which public health actions are recommended. The CDC recommends case management for children with blood levels of five or higher. There appears to be a dose response relationship between blood lead level and neuropsychological outcomes, although recent research has documented mild neuropsychological deficits even at low lead levels.
<30 = low, > 80 can result in lead encephalopathy, >44 = pharmacological intervention

Presentation, disease course, and recovery: signs of acute elevated lead levels include headache, irritability, abdominal pain, vomiting, weight loss, attention problems, hyperactivity, learning problems, and slowed speech development.

Expectations for neuropsychological assessment results: declines in IQ and academic achievement have been documented even at low blood lead levels. The most common neuropsychological domain affected by lead exposure is executive functions. Deficits in visuospatial skills are also commonly found. Children exposed pre- or postnatally to elevated lead levels are often restless, impulsive, inattentive, and aggressive. Elevated levels of both internalizing and externalizing behavior disorders have been documented, including increased rates of ADHD and odidi. In later childhood and young adulthood, individuals with a history of elevated blood lead levels are more likely to engage in juvenile delinquency and antisocial behaviors. These difficulties are seen more commonly in males than females.

Treatment considerations:
–age considerations: children absorb approximately 50% of ingested lead, whereas adults only absorb 10 to 15%. More severe neurocognitive and neurobehavioral effects are seen when lead exposure occurs in utero and during infancy, as opposed to during later childhood and adulthood.
Chelation treatment: Blood lead levels of greater than 44 are often treated with chelation therapy. this uses dimercaptosuccinic acid to trap lead in the body and remove the lead through urine. This treatment is effective in reducing blood lead levels but is likely not effective in reversing cognitive or behavioral deficits.

Methodological considerations: use of biomarkers of exposure, such as blood levels and blood, hair, teeth, and breast milk, are relied on as measures of lead exposure. Exposure to lead is not a random event. Numerous confounding variables exist, including lowered parental IQ, worse SES, maternal drug use, and poorer caregiving quality.

Question 96

Other toxic substances with Neuropsychological Relevance

Answer 96

Nicotine/tobacco
Nicotine exposure in utero can lead to reduced fetal oxygen supply, fetal undernourishment, and basil constrictor effects on the placenta and umbilical cord. Equivocal findings regarding neuropsychological effects. Externalizing behavior disorders are common, particularly ADHD.
Amphetamines
Motor deficits are seen during infancy. Deficits in executive functions during childhood. Poor emotional regulation.
Opiates
In utero exposure to opioids, predominantly heroin, can lead to decreases and neuroplasticity and increase cell death. There is also an increased risk for lower birthweight. Motor deficits during infancy with later deficits in executive functions and ADHD symptoms during childhood.
Pesticides
Organophosphate pesticides disrupt the enzyme that regulates the cetyl choline. Prenatal exposure to Ops has been linked to various neuropsychological and behavioral deficits in childhood.
Air pollution
Animal models suggest that particulate matter in air pollutants can cross the blood brain barrier and affect the developing brain. Studies have documented slightly lower IQ scores, as well as academic and behavioral deficits, in children exposed prenatally to high levels of air pollution.
Prescription medications
-Exposure to anti epileptic medications during the first trimester can lead to major anatomical birth defects whereas exposure during the third trimester has been linked to cognitive and behavioral deficits. Valproic acid and polytherapy appeared to have the most significant risk. Exposure to valproic acid has been linked to verbal deficits, as well as increased risk for ADHD and autism.
-In utero exposure to the blood thinner warfarin has been linked to developmental delays and dandy Walker malformation
-in utero exposure to the acne medication accutane or isotretinoin has been linked to an increased risk for birth defects and ID.
-In-utero to SSRI’s can lead to neonatal abstinence syndrome, but the long term effects, if any, are unknown.

Question 97

Acrodynia (“painful extremities”)

Answer 97

primarily affects young children exposed to mercury. It is often misdiagnosed in children as measles, other viral exanthems, or Kawasaki disease. symptoms include irritability, photophobia, pink discoloration and edema of the hands and feet, hair loss, irritability, anorexia, insomnia, poor muscle tone, profuse sweating, and polyneuritis.

Question 98

neonatal abstinence syndrome

Answer 98

a non specific group of symptoms that can be displayed by some newborns whose mothers used illicit or prescription drugs during pregnancy. Symptoms are variable but may include excessive crying, irritability, hyperactive reflexes, seizures, and increased muscle tone.

Question 99

reference dose

Answer 99

And exposure without recognized adverse effects

Question 100

Meningitis

Answer 100

meningitis is an infection or inflammation that is confined to the meninges. The most common cause of meningitis are bacteria or viruses, although other causes also exist (e.g., fungal). outcomes tend to be much worse when the etiology is bacterial as opposed to viral.

Question 101

Bacterial forms of Meningitis

Answer 101

95% of cases of meningitis are caused by three primary agents:
-Haemophilus influenzae type B (Haemophilus meningitus)
-Neisseria meningitides (Meningococcal meningitis)
-Streptococcus pneumoniae (Pneumococcal meningitis)
Bacteria may spread to the meningitis in several ways, including from an adjacent infected area, such as the ears or sinus is; from the environment through a penetrating injury or congenital defect; And through the bloodstream (hematogenous dissemination), which is the most common cause.
The primary cause of brain damage and bacterial meningitis is inflammation, which leads to tissue and vascular injury (vasculitis), septic thrombosis, and smaller infarcts. Other complications include brain (cerebral) edema and increased intracranial pressure, which can lead to hypoxic ischemic encephalopathy. The pathophysiology of increased intracranial pressure is complex and may involve many proinflammatory molecules, as well as mechanical elements. Cranial nerve defects may also be present (although these are often reversible) and are more common in children (~5-11% of cases) then adults with bacterial meningitis. Although any of the cranial nerves can be affected in meningitis, the 8th cranial nerve (auditory) is most often impacted, which can result in sensorineural hearing loss. When there is increased intracranial pressure, the most commonly involved nerve is the 6th cranial nerve (abducens) because it has the longest route and is most vulnerable to compression. The third, 4th, and 7th cranial nerves may also be impacted.

Individuals with tuberculosis can also develop meningitis, which is caused by the bacteria mycobacterium tuberculosis. The tuberculosis bacteria is spread to the brain and spine from another place in the body, usually the lung. Tuberculous granulomas, or rich folci, release bacteria into the subarachnoid space, resulting in tuberculosis meningitis.

Epidemiology
bacterial meningitis: 0.6 to 4 cases per 100,000 annually of all ages. neonatal bacterial meningitis occurs in .25- 1 cases per 1000 live births. TB meningitis is rare in the United states. It occurs mainly in resource- poor regions with a high tuberculosis burden.
Mortality: mortality from bacterial meningitis has been estimated to be 5 to 10% overall, which is a dramatic improvement relative to the 1950s prior to the development of antibiotics, when rates were near 90%.
-Age: Mortality rates are highest in the first year of life, decline in mid life, and increase again in older adults.
-Type: mortality rates are highest in pneumococcal (10-30%) and lowest with meningococcal (4-5%).
-mortality rates are also high in TB meningitis (15-30% in most studies, much higher rates in HIV positive individuals).

Morbidity: Long term neurologic and/or neurobehavioural sequelae are seen in approximately 15 to 25% of survivors of bacterial meningitis. In developed countries, the most common long term sequella include hearing loss (approximately 11%), intellectual disabilities (4% ), spasticity/paresis (4%), and seizure disorders (4%). more broadly, approximately 50% of childhood survivors of bacterial meningitis have at least one negative sequelae more than five years after diagnosis, the most common of which (78%) fall in the category of cognitive or behavioral difficulties (cognitive impairments, academic limitations, ADHD).n data on outcomes from TB meningitis are limited. Early research has been mixed, but suggests that many survivors are left with mild to moderate disability.

determinants of severity:
age factors: the highest prevalence of bacterial meningitis occurs in children less than five years old and older adults 60 and over. Meningococcal meningitis Is also more common in college students, (freshman in particular) who reside in dormitories. Children are also at higher risk of mortality than adults. The risk of death from bacterial meningitis is 15 to 20% in neonates and three to 10% in older children. Ranges are given because mortality risk also depends on the type of meningitis.
Medical risk factors: one of the biggest medical risk factors for contracting bacterial meningitis is immunosuppression because this leads to an increased risk for opportunistic infections. Individuals with HIV and other medical conditions with poor immune functioning (or who are immunosuppressed due to treatments they are undergoing) or presumed autoimmune etiologies are also at higher risk for bacterial meningitis; This includes individuals with cystic fibrosis, diabetes, hyperparathyroidism, and renal or adrenal insufficiency.
Cultural/Economic Risk factors: These impact both the development and treatment of bacterial meningitis. Incidents and complication rates are higher in developing countries. It has been suggested that prevention through large scale vaccination programs is likely to be the most cost effective strategy for improving the situation in these countries. These factors are also important to consider in TB, as the disease tends to impact countries and individuals with fewer resources. For example, one study in India found that 80% of children with TB meningitis who underwent neurodevelopmental follow up demonstrated deficits in loco motion, language, word nation, and personal, social, and executive function, despite many having made a good clinical outcome. These deficits are compounded by the fact that most of these students are reared in impoverished homes with limited child caring options, and from communities with a shortage of schools able to provide adequate support.

Risk factors that influence Neuropsychological/Neurological Outcomes:
In some studies, individuals with pneumococcal meningitis have been shown to demonstrate greater cognitive impairments and neurological sequelae such as hearing loss than those with meningococcal meningitis. Poor outcomes from TB meningitis often relate to the neurological complications which include stroke, seizures, and hydrocephalus. Viral (aseptic) forms have better outcomes than bacterial forms.
Risk factors in children
-acute- phase neurological complications including prolonged seizures, hemiparesis, coma, and bilateral hearing loss have been associated with worse outcomes.
-Low CSF glucose levels, streptococcus pneumoniae infection, and two or more days of symptoms prior to admission have also been linked to worse outcomes in children
-younger age at the time of illness, particularly underage 1, contributes to worse language outcome. This is consistent with research and other pediatric disorders in which diffuse brain injuries and young children have been shown to be associated with delayed consequences in cognitive development, in this case reduced plasticity for language.
-Male gender may also be associated with worse behavioral outcome.

Presentation, disease course, and recovery

• acute versus gradual
  
  • acute (several hours): cardinal signs include sudden fever, severe headaches due to inflammation of the meningeal blood vessels, and nuchal rigidity or stiff neck.
  • Gradual (several days): often nonspecific “flu like” symptoms.
• Most common presenting symptoms in children include hyperthermia, lethargy, anorexia or vomiting, respiratory distress, convulsions, irritability, jaundice, bulging fontanelle in infants, diarrhea, and nuchal rigidity.

Assessment methods

• lumbar puncture: the diagnosis of bacterial meningitis is confirmed by the presence of bacteria in the CSF. CSF can also be examined for the presence of blood or white blood cells (elevations would suggest presence of an infection), high protein levels, and low glucose. CSF is also examined in TB meningitis.
• Brain imaging: although brain imaging studies may also be used in the work up for meningitis, CT scans of the head and MRI of the brain generally do not aid in the diagnosis of bacterial meningitis. Some patients may show meningeal enhancement, but its absence does not rule out the condition. MRI is used in TB meningitis to visualize leptomeningeal tubercles, to identify TB meningitis related cranial neuropathies, and to diagnose other complications of TB, such as stroke.

Treatment

• Antibiotics: for several types of bacterial meningitis, including oral and IV in more severe cases.
• vaccine for several types of meningococcal meningitis.
• Corticosteroids treat inflammation and brain swelling and may be helpful in preventing neurological sequelae and hearing loss in some types of meningitis. Several years ago, dexa methadone treatment was recommended as an adjunct to the standard of care treatment for adults with bacterial meningitis. Although several earlier studies suggested improved morbidity and mortality with adjunctive dexamethasone, more recent findings have not fully substantiated these claims, calling into question this recommendation.
• For TB meningitis, treatment includes anti- tuberculosis drugs and adjunctive corticosteroids.

Recovery course: after medical stabilization, children and adults with meningitis (and encephalitis) sometimes require inpatient or outpatient rehabilitation. The length of stay is variable depending on the severity of the illness. With the exception of cases in which there is also spinal cord involvement (eg, encephalomyelitis), individuals with these conditions tend to show greater residual impairments in cognitive as opposed to physical domains.

Question 102

Paraneoplastic syndrome

Answer 102

Arises from autoimmune reaction to cancers. Autoantibodies are though to underlie the symptomatic presentation, and several types of autoantibodies have been found. The neurological manifestations can precede cancer diagnosis. These syndromes can include more “classical” symptom presentations (e.g., Lambert-Eaton myasthenic syndromes, subacute cerebellar degeneration, and in peds populations myclonis/opsoclonus) or those that can be due to cancer or can present as another disease (e.g., amyotrophic lateral sclerosis, polymyositis, and/or polyneuropathy). The 5 common syndromes include:

1. Brain and cranial nerves: limbic encephalitis or other dementia, optic neuritis, brain-stem encephalitis, opsoclonus-myoclonus, or subacute cerebellar degeneration.
2. spinal cord and/or dorsal root ganglia: motor neuron disease, myelitis, myelopathies, sensory neuronopathy, subacute motor neuronopathy.
3. Peripheral nerves: autonomic neuropathy, Guillan-Bare syndrome, mononeuritis-multiplex and vasculitic neuropathy, subacute sensorimotor peripheral neuopathy.
4. Neuromuscular junction and muscle: Lambert-Eaton myasthenic syndrome, dermatomyositis, myotonia, myasthenia gravis, acute necrotizing myopathy, neuromyopathy.
5. Unknown or combined central and peripheral nervous system: encephalomyelitis, neuromyopathy, stiff-person syndrome.

Paraneoplastic syndrome is a diagnosis of exclusion that can be confirmed by tests for autoantibodies. Onset of symptoms is subacute, inflammatory CSF with increased protein and oligoclonal bands, severe neurologic disability, and stereotyped presentation that often affects a specific aspect of the CNS. This is thought to reflect the immune response to injury, with a directed autoimmune response to antigens of the tumor and shared nervous system components. The presence of autoantibodies can also assist in the search for underlying cancer. When a paraneoplastic syndrome is present, it suggests a more morbid disease course than the same tumor without a paraneoplastic syndrome.

Diagnosis and Neuroimaging
Tumors are diagnosed and removed during surgery. A variety of different conditions- particularly those that cause increased ICP or produce progressive neurologic symptoms- need to be ruled out when differentially diagnosing brain tumors. These can include subdural hematomas, hydrocephalus, brain abcesses, cerebral infarctions, ms, and AD. Brain biopsy is required to establish histopathologic features, but sometimes to confirm the presence of a brain tumor because some conditions can appear like a brain tumor (brain abscesses, demyelinating disease). A biopsy may be contraindicated in vital areas, such as brain stem (e.g., brain stem gliomas).
CT and MRI are essential in screening for brain tumors and in differential diagnosis (ruling out hemorrhages/stroke). MR imaging, using gadolinium infusion or not (or “with and without contrast”), is considered the best method of determining the mass’ characteristics, which includes location, size, and extent of edema. Gadolinium pools around cancer cells, making them appear brighter (contrast-enhanced). While not routinely used (due to limited availability and high cost), PET is useful to provide information about blood flow, metabolism, and physiology of brain tumors and surrounding areas. Functional MRI is useful in cortical mapping during tumor resection, which enables surgeons to avoid damaging eloquent language and motor cortices.

> Definitive diagnosis requires brain biopsy
A brain biopsy establishes histopathologic features needed to classify or grade brain tumors.

Question 103

WHO 4-tier grading system for brain tumors.

Answer 103

Grade 1 and 2: low grade. 3 & 4: high grade
Grade I: eg. Pilocytic astrocytoma and meningioma. These tumors are benign, grow slowly, and have low proliferation potential. Clearly defined borders. Tend not to recur.

Grade 2: e.g., oligoastrocytoma and pineocytomas. Also have low proliferation potential, however, unlike Grade 1, they often recur and are “infiltrative in nature”. Thus, grade 2 and higher suggest malignancy. Slow growing, but with poorly defined borders and greater potential for recurrence.

Grade 3: eg. Anaplastic astrocytoma and anaplastic oligodendroglioma. Generally malignant, with high proliferation potential, and usually grow again after being removed. Patients with grade 3 and above typically receive radiotherapy and/or chemotherapy, in addition to undergoing neurosurgery.

Grade 4: e.g., glioblastoma multiforme and medulloblastoma. Most aggressive, and most difficult to treat. They also appear very different from normal cells. Not encapsulated. Identified in multiple areas in the brain.
>grading tumors requires histologic sample

Question 104

Brain tumor survival rates

Answer 104

Grading is used to predict how the tumor will behave and is related to survival rates.
Grades 1 & 2 have 50% greater survival rate than 3 & 4. Mean survival rates for grade 2 are 5-10 years; 2-3 years for grade 3; and 1-1.5 years for grade 4. Other influencing factors include age, extent of tumor removal, tumor progression, and the location of the tumor.

Question 105

Brain Tumor treatment

Answer 105

Surgery, radiation, or chemotherapy. Dexamethasone, a steroid, is often used to reduce swelling and anti-seizure medication may be given to reduce seizures. There are also other bioimmunotherapy and hormonal therapies.

Tumor Treatment: Radiation
Whole brain radiation therapy is typically employed for brain metastases, irrespective of the number of lesions or location of the tumor.

Radiation improves survival over surgery alone, however, side effects are common. These include anorexia, nausea, and fatigue. Neuroanatomic damage can occur but yet to be determined specific regions most sensitive to the effects of radiotherapy. Generally, affects the white matter tracts and cerebral vasculature, due to axonal demyelination and disruption to vascular endothelial cells, respectively. Radiation is not indicated for children who have undergone complete or nearly complete surgical resection because tumor progression is unlikely. And risk are high to developing brain, so should only be considered when tumors are not well defined and noninfiltrative. In kids, associated with loss of white matter volume or failure to develop white matter at an appropriate developmental rate. Compromised white matter integrity is associated with poor intellectual functioning.
IQ scores generally used to measure diminished global cognitive functioning in children who have undergone radiotherapy. Adverse effects appear to be dose and age dependent, in that very young children (<4) are most susceptible to cognitive deficits. Thus, chemotherapy is often used to postpone radiation therapy, to allow children’s brains to develop as completely as possible- especially in children under 2.

Tumor Treatment: Gamma Knife/Stereotactic Radiosurgery
Stereotactic radiosurgery or gamma knife neurosurgery directs focused gamma radiation to a highly circumscribed area, often in a single dose. Gamma-knife neurosurgery has been recommended for targeting smaller tumors (<3 cm diameter), and, although complications have been documented (facial numbness and hearing loss), these are rare due to minimal radiation exposure. Given its focal delivery, accurate delineation of cancer tissue is critical and usually involves MRI planning.

Tumor Treatment: Chemotherapy
Chemotherapy is designed to “poison” cancer cells, and disrupt cell proliferation. Chemotherapy is administered orally or intravenously. Another option is to place a dissoluble wafer (Gliadel wafer) directly on the tumor site (tumor bed) after surgical resection.

Chemo has immediate and delayed side effects. Nausea and vomiting are common within 24 hours of treatment. Leukopenia (reduction in white blood cells) and stomatitis (inflammation of the mucous lining in the mouth) can occur within days to weeks. Cardiomyopathy and peripheral neuropathy, with the latter being the most common neurological complication of chemo, can occur within weeks to months of treatment.
Some agents in chemo are known to have neurotoxic effects and can cause diffuse white matter changes. Can cause persistent cognitive deficits (chemobrain) in approximately 18% of patients, for all cancer types. Such effects have been observed 2 years after chemo is discontinued. Chemo may cause deficits of attention, PS, verbal memory, visual-spatial functioning, executive functioning, and/or motor functioning. Confusion, mental fog, fatigue, and significant mood disturbances are subjective complaints of chemo. In kids, attention and EF problems are most common remaining symptom.

Question 106

Brain tumor: Test battery

Answer 106

Keep it brief- due to fatigue potential, but hit all domains. Sensory and motor tests are also recommended, if there is time.
RCI: given that NP evals are sometimes used serially for individuals suffering from brain tumors, we recommend clinicians consider employing measures for which reliable change indices can be calculated (or are known).

Question 107

Chronic neuropsychological symptoms of neurotoxicity

Answer 107

Effects on attention/concentration, executive function, learning, information acquisition and consolidation, and emotion. Autonomic functions are also often adversely affected.

Question 108

Neurotoxicity

Answer 108

The harmful effects of neurotoxicants on the nervous system, which can adversely affect cognitive, emotional, behavioral and physical domains. Neurobehavioral toxicity describes the adverse effects of neurotoxicants via neural processes on behavior and neuropsychological function. They symptoms and signs of neurotoxicity may include aspects of neurological, cognitive, behavioral, and affective dysfunction, as neurotoxicants can damage any nervous system structure or function. Most commonly encountered neurotoxic substances include solvents, metals, pesticides (organophosphates), carbon monoxide, and mold.

Question 109

Organic Solvents (Glues, cleaning materials, varnishes, etc)

Answer 109

A solvent is a liquid or gas that dissolves a solid, liquid, or gas, resulting in a solution. The most common solvent in everyday life is water. Most other commonly used solvents are organic chemicals, termed organic solvents. Solvents usually have a low boiling point and evaporate easily, leaving the dissolved substance behind. Common uses for organic solvents are in dry cleaning, as paint thinners, as nail Polish removers and glue solvents, in spot removers, and detergents, in perfumes, and in chemical syntheses. many fuels are neurotoxic solvents, including gasoline and diesel.

Question 110

Metal

Answer 110

A metal is a chemical element whose atoms readily lose electrons to form positive ions, and form metallic bonds between other metal atoms and ionic bonds between nonmetal atoms. A heavy metal is a member of an ill defined subset of elements that exhibit metallic properties. Common metals with neurotoxic effects include arsenic, cadmium, lead, manganese, mercury, and thallium. Manganese can cause a parkinsonian syndrome due to extrapyramidal dysfunction. Manganese exposure has been reported to result in neuropsychological and psychological impairments. A primary target of manganese appears to be the dopaminergic neurons in the striatum. Labeled as manganese induced parkinsonism, the movement disorder has many features similar to idiopathic Parkinson’s disease, but there are differences, including reduced response to leva dopa treatment. Some research suggest that welders are at an increased risk for development of parkinsonism, with greater prevalence of parkinsonism and and onset of symptoms at an earlier age. However a recent large study failed to show an increased risk for mortality due to parkinsonism or other neurodegenerative diseases for welders when compared to other peers. Neuropsychological deficits from manganese include impaired psycho motor speed, visual motor or visual perception skills, verbal fluency- phonemic, working memory or divided attention, and delayed memory. High rates of depression, anxiety, and confusion has also been reported

Question 111

Pesticides

Answer 111

a substance or mixture of substances used to kill a pesticide. A pesticide may be a chemical substance, biological agent (such as a virus or bacteria), antimicrobial, disinfectant or device used against any pest. Common pesticides include organo phosphates, organochlorines, synthetic pyrethroids and toxic metals.

Question 112

Gases

Answer 112

some gases are toxic (e.g., chlorine), while others can be classified as simple asphyxiants. some toxic gases are corrosive (e.g., chlorine), in which damage is done directly to tissues and organs (chlorine damages lungs). asphyxia is a condition of severely deficient supply of oxygen to the brain from dysfunctional respiration. Hypoxia describes the condition of reduced oxygen supply to the brain.

An asphyxiant gas is an otherwise non toxic or minimally toxic gas which dilutes or displaces oxygen and creates a deficient supply of oxygen to the brain, which can result and hypoxia and ischaemia.
carbon monoxide is a colorless, odorless, tasteless, yet highly toxic gas. Its molecules consist of 1 carbon atom covalently bonded to one oxygen atom. It is produced from the partial oxidation of carbon containing compounds, notably in internal combustion engines and gas heaters. Carbon monoxide forms in preference to the more usual carbon dioxide when there is a reduced availability of oxygen present during the combustion process. Carbon monoxide is produced by common household appliances, such as gas space and water heaters. When not properly ventilated, carbon monoxide emitted by these appliances can concentrate to toxic levels. The most common symptoms are headache, dizziness, weakness, nausea, vomiting, chest pain, and confusion. High levels of inhalation can cause loss of consciousness and death. the effect of carbon monoxide poisoning may not be dose dependent in some cases, as patients with less severe poisoning have exhibited similar cognitive and emotional impairment as those exposed to higher levels.

Question 113

Mold

Answer 113

Mold neurotoxicity describes the poisonous effects on the human nervous system of mold, mycotoxins and bacteria, which can result from repeated indoor water intrusions. The most common toxic molds include Stachybotrys chartarum (S. chartarum), Aspergillus spp, Cladosporium spp, Fusarium spp, and Penicillium spp.
Symptoms of chronic mold neurotoxicity include difficulty with concentration, learning/memory, sleep, headache, executive dysfunction, personality changes, and other cognitive impairments.

Question 114

Definition of Exposure and Symptom Terms for Neurotoxic Agents

Answer 114

Acute exposure is defined as contact with a substance that occurs once or for only a short time (up to 14 days)

Acute effects: health effects that appear at the time of, or soon after exposure, that persist in a biologic system for only a short time, generally less than a week. The effects can range from symptomless signs, to behavioral changes, to death.
Intermediate duration exposure: contact with a substance that occurs for more than 14 days and less than a year.

Chronic exposure: contact with a substance that occurs over a long time (more than a year).

Chronic health effect: an adverse health effect persisting for months or years.

Question 115

The Neurotoxicity Syndrome

Answer 115

used or proposed to describe the constellation of chronic symptoms of individuals with neurotoxic exposure. The syndrome reportedly may present from both high-level or repeated low-level exposures.
Used to describe the characteristic constellation of symptoms and signs of neurotoxicity. The WHO ICD-10 refers to neurotoxicity affecting the brain as “toxic encephalopathy.” But they have no description of symptoms or signs associated with it. The NS presents CNS and PNS signs and symptoms.
CNS dysfunction can result in deficits in memory (Recent learning and information retrieval) and attention/EF (Planning, inhibiting responses, strategy development, judgement, problem solving and solution implementation). Mood affects can include increased irritability, anxiety, and/or depressive symptoms and/or personality changes. Autonomic dysfunction can result in disruption of sleep (excessive awakenings) along with reduced energy (fatigue) and libido.

Question 116

Acute and chronic symptoms of Organophosphate poisoning (pesticides)

Answer 116

Symptoms will be many b/c of the widespread nature and function of the various neurochemical receptors affected by Ops. Acute exposure to high level OPs can lead to a variety of acute symptoms affecting multi-organ systems including: cardiovascular, respiratory, gastrointestinal, genitourinary, glandular, and neurological.
Muscarinic effects by organ systems include the following:
–Cardiovascular: bradycardia, hypotension
–respiratory: rhinorrhea, bronchorrhea, bronchospasm, cough, severe respiratory distress
–gastrointestinal: hypersalivation, nausea and vomiting, abdominal pain, diarrhea, fecal incontinence
–Genitourinary: incontinence
–Ocular: blurred vision, miosis
–Glands: Increased lacrimation, diaphoresis

Nicotinic symptoms: include muscle fasciculations, cramping, weakness, and diaphragmatic failure.
Autonomic effects: hypertension, tachycardia, mydriasis, and pallor.
CNS effects: anxiety, emotional lability, restlessness, confusion, ataxia, tremors, seizures, and coma.

Organophosphate high level exposure acute effects mnemonics: SLUDGE and DUMBELS
Salivation
Lacrimation
Urination
Diarrhea
GI Upset
Emotional

Diaphoresis and diarrhea
Urination
Miosis
Bradycardia, bronchospasm, bronchorrhea
Emesis
Lacrimation (excess)
Salivation
Chronic symptoms of Organophosphate poisoning (pesticides)
Acute symptoms and the symptoms that are more similar to chronic symptoms of many neurotoxic substances.
–impaired vigilance and reduced concentration (impaired attn, concentration, vigilance, and EF)
–slowing of information processing and psychomotor speed
–memory deficit
–linguistic disturbance (verbal fluency deficit)
–depression
–anxiety and irritability

Can also have other psych sequelae. Ops may have a proclivity for promoting anxiety disorders.

Question 117

Acute and Chronic effects of Lead exposure

Answer 117

Acute: may include lethargy, abdominal cramps, anorexia, and irritability, and can progress to vomiting, clumsiness, ataxia, alternating periods of hyperirritability and stupor, and then finally seizures and coma.
Chronic: profile more variable in children. Otherwise similar to the chronic effects of OP poisoning. Can exhibit learning disorders and lower IQ at high-level exposure.
deficits in fine motor skills (particularly in children), attention/concentration, learning and visual memory, cognitive inflexibility/executive dysfunction

Question 118

Examination for Neurotoxicity

Answer 118

Take thorough history. Symptoms can be exacerbated by pre-existing symptoms. Symptoms appearing de novo or pre-existing symptoms that are exacerbated could be due to neurotoxicity, and need to be interpreted in light of a comprehensive neuropsychological evaluation. Neurotoxicity may exacerbate the underlying weaknesses, proclivities, and habits.

Overall, reduced performance on speeded attention and divided attention tasks are most common in chronic NS. Other idiosyncratic chronic symptoms can also develop.

• neuro exam, urine testing (helpful acutely and for longer periods with metals), blood assays (only for acute), antimyelin antibody measure can be elevated in neurotoxic conditions and can provide helpful corroborative evidence for neurotoxic exposure and chronic effects.
• nerve conduction velocity tests to evaluate peripheral nerve function.
• EEG: often used in acute encephalopathy cases, but is less helpful in chronic neurotoxicity cases. (but often not very helpful)
• Autonomic function studies including cardiac function tests may be helpful for documenting autonomic dysfunction. However, findings in this arena also are not specific to neurotoxicity.
• sleep studies. Sleep apnea is a common problem resulting from neurotoxicity, although it can result from other causes of CNS decline as well, or other causes. Its 14x more prevalent among solvent-exposed workers compared with the general population, and was found in 39% of patients referred for investigation of possible organic solvent encephalopathy.
• Neuroimaging: routine CT and MRI can be helpful to rule out other causes of pathology. Brain atrophy and/or WM changes can sometimes be found with neurotoxicity. Changes in brain metabolism have been reported in PET and SPECT.
• Neuropsych: comprehensive.

Question 119

Neuropsychological findings and meningitis

Answer 119

Adults:
average IQ, decreased attention (low on trails B and stroop), weak in processing speed and reaction time-possibly one of the main weaknesses. generally no problems are found in language or visual spatial function although a few studies have noted mild visual spatial processing weaknesses. Executive function problems are common. Subtle executive function problems are a relatively consistent finding in adults. Sensorineural hearing loss is the most common sensory finding. Complications can also include hemiparesis, cortical blindness, and ataxia, which typically resolve. Most are able to return to premorbid levels of functioning and work as usual.
Children:
low average to average IQ; 4% in developed countries diagnosed intellectual disabilities. Twice as likely as controls to require special education assistance. More likely to repeat grade or at least in special needs. Academic issues may be more related to problems in attention, speed, and executive functioning skills.
Higher attention problems, with parents and teachers endorsing more ADHD symptoms. Language problems in children who contract meningitis before the age of 1. Children are not severely impaired and executive functions but their abilities are often below developmental expectations. Sensorineural hearing loss is the most common sensory finding. Complications can also include hemiparesis, cortical blindness, and ataxia, which typically resolve. Long term spasticity or paresis occurs in about 4% of children with a history of bacterial meningitis. Behavioral changes including ADHD are common. Adolescents show poorer quality life, greater fatigue, reduced social support, and reduced overall mental health when to three years after illness.

Question 120

Aseptic forms of meningitis

Answer 120

Neuropathology: the term aseptic refers to non bacterial forms of meningitis caused by viruses, fungi, and parasites. Enteroviruses (virus is transmitted through intestines) are by far the most common cause of aseptic meningitis, greater than 85%. These viruses are a genus of single stranded RNA associated with several human and mammalian diseases. There are several types of fungi that can cause meningitis including cryptococcus, histoplasma, etc. Candida is often acquired in a hospital, while the other types are typically acquired when fungal spores are inhaled from the environment.
Epidemiology: Viral forms of meningitis are more common than bacterial. It is more common in children and young adults and often present in the summer months when enterro viruses are more common. Fungal meningitis is rare and typically but not always occurs in individuals who are immune compromised, including those who are HIV positive. Cryptococcus is most common for those with weak immune systems. This disease is one of the most common causes of adult meningitis in Africa. Premature babies with very low birth weight are also at increased risk for getting candida bloodstream infection, which may spread to the brain.
With the exception of neonates, the rate of mortality for viral meningitis has been estimated to be less than 1%.
Long term neurologic and or neurobehavioral sequelae are far less common in viral versus bacterial meningitis. Most people recover within 7 to 10 days and have no residual neurologic deficits. When there are persistent deficits, they tend to be mild.
Presenting symptoms: severe headache is the most common presenting symptom. Fever is also common, often low grade in the prodromal stage with higher temperature elevations at the onset of neurological signs. Other common symptoms include irritability, nausha, vomiting, stiff neck, rash, or fatigue. In terms of the timing, nonspecific flu like symptoms and low grade fever precede neurologic symptoms by approximately 48 hours.
Assessment methods: lumbar puncture and blood work. EE G or other imaging techniques and complex cases. These additional tests are most relevant in cases where there is an additional suspicion of encephalitis or a subclinical seizures.
Treatment: for viral, antibiotics are ineffective. Treatment for viral meningitis is mostly supportive (i.e., rest, fluids, pain and anti-inflammatory medications), although patients may undergo additional treatments with antiviral medications.
treatment for fungal meningitis includes antifungal medication

Recovery: Viral typically has a relatively benign course, with symptoms often resolving in 1-2 weeks. Long-term sequalae are quite rare.

NP expectations: not a ton of studies. When NP impairments have been noted, they tend to be mild to moderate in nature and in domains of attention and speed.
West Nile Virus (neuroinvasive) disease linked to impairment in motor functioning, verbal learning and memory, and aspect of executive function.

Individuals with cryptococcal (fungal) meningitis have been shown to demonstrate broad deficits in cognition in the early stages of the disease, with improvements noted over the first year of recovery. Longer lasting deficits have been noted in motor speed, gross motor and executive functioning. If shunt is required this is associated with worse outcomes.

Question 121

Encephalitis

Answer 121

A general term that refers to an infection of the brain tissue or parenchyma.

neuropathology: viruses are the most common cause of encephalitis, although it can also be caused by various bacteria, fungai, and parasites. Autoimmune encephalitis is also common and involves the body’s own immune system attacking the brain.
Primary: Also known as acute viral encephalitis, refers to a direct infection of the brain through direct invasion of a pathogen
secondary: also known as post infective encephalitis, results from either a previous viral infection (most commonly chickenpox, mumps, or measles), for an immunization (measles vaccination), or via an immune response.
Most viruses reached the CNS via the bloodstream. Some viruses, such as HSV, travel to the CNS along cranial nerves. Herpes simplex virus remains dormant in the trigeminal ganglia. If activated, it is believed to travel along the trigeminal nerve into the brain. Viruses use cellular machinery for their replication and damage or kill the cells they infect. Brain damage is also caused by the cell mediated immune reaction viruses and cancers elicit. Activation of T lymphocytes by viruses or cancers includes the release of potent cytokines and mobilization of macrophages that not only attack the viruses or cancer but assault the host, causing severe vascular and tissue injury. Some viruses and types of encephalitis have predilection for certain types of neurons or brain regions and may have a characteristic pattern on neuroimaging including involvement of the cerebellum brainstem and basal ganglia. Lesions in the thalamus, basal ganglia, and midbrain are observed in eastern equine encephalitis While temporal lobe pathology and enhancement of orbital frontal lobes are seen in HSV encephalitis. However, in neonates who develop HSV encephalitis, cortical lesions are seen within 48 hours but then often progress to subcortical white matter lesions within a week. Bilateral subcortical abnormalities are associated with poor cognitive and motor functioning.
-HSV encephalitis is the most common cause of encephalitis in children and the most common severe form of encephalitis and is estimated at 2000 cases per year in the United states.
Mortality rates for encephalitis are estimated to be 5% overall and 3% in children, although the range is quite varied depending on the specific type. Some types have greater mortality in the elderly. The highest mortality is for rabies virus encephalitis at virtually 100% and HSV encephalitis if not treated (50% of children die if left untreated). approximately 1/3 of individuals with encephalitis of all forms have some ongoing neurological or cognitive difficulties at the time of their discharge from the hospital children who fully recover are most likely to do so within 6 to 12 months. Severity is greatest in infants and the elderly. Prevalence rates are highest in children and young adults.

Individuals with HSV encephalitis have been found to have more cognitive and psychiatric impairments than those with other ideologies, including two to four times the risk of cognitive impairment.
In children, those with longer hospital stays, confirmed infectious agent, and abnormal neuroimaging are less likely to fully recover and may report poor quality of life. Outcomes also vary greatly by etiology. Children with HSV often have long term neurological impairment, particularly following a delayed start of acyclovir. older infants and young children with encephalitis from enteroviruses usually recover fully, though neonates vary, some with significant long term deficits.

The 20 year risk for development of seizures is approximately 20% for those with early seizures and 10% without early seizures.

Presentation:
Acute: hours to days. Presents with severe headache and fever often resembling influenza, as well as altered consciousness, disorientation, behavioral and speech disturbances, in general and focal neurological signs.
Subacute: Weeks. Presents with seizures and speech disturbance after a few weeks of altered behavior.
Chronic: Can present or progress over the course of years and produce acute symptoms only occasionally, such as HIV infection or untreated Lyme disease.

Behavioral presentation: Encephalitis can initially present in the form of behavioral or psychotic disorder, particularly in HSV, with symptoms ranging from delusions, hallucinations, and affective disorders, such as depression, aggression, and euphoria. A small number of HSV encephalitis cases present with symptoms of Kluver-Bucy syndrome due to bilateral damage to the amygdala.

Assessment: Lumbar puncture/bloodwork, EEG (for possibility of seizures. Tend to be nonspecific w temporal focus in HSV), CT and MRI (to identify swelling, localized infection, mass effect, and other signs of inflammation. With contrast to look for signs of infection, including meningeal enhancement. MRI with a diffusion sequence may be preferred in these instances as it best differentiates among tumors, strokes, and abscesses).

Treatment:
antiviral drugs: such as acyclovir and ganciclovir, are used to treat viral
Anticonvulsant drugs may be prescribed to prevent future seizures.
Cortico steroid drugs are used to reduce swelling and brain inflammation.
Hemispherectomy may be used to treat rasmussen’s encephalitis and often appears to slow down the neurological deterioration in pediatric cases.

NP FINDINGS:
Adult:
IQ: low average to average. Lower than estimates by .5-1 SD
Attn: subtle problems. PS commonly affected. Anterograde memory impairment in HSV (25-75%) and west nile. EF are one of most commonly reported problems in 40% of cases of HSV. May see elevated psych symptoms. Generally good outcomes and return to work but may take months to a year.
Unaffected: language (although naming and severe aphasias have been seen in HSV), visuospatial, sensorimotor (rare but most reported in west nile),

Kids: IQ- low average to average. Higher rate of LD, neonates have more variable outcomes for ID to average. Higher attention problems. PS affected. Not typically language or visuospatial. Memory same as above (anterograde), EF most commonly affected. Sensorimotor as above. More likely to demonstrate behaviorral difficulties. Higher attention problems, hyperactivity-impulsivity, oppositional behavior, and in some cases, psychiatric problems. Some case studies with Kluver-Bucy in rare instances.

Impact of HSV
Connection between chronic HSV and cognition, even in cases where there is no acute encephalitis episode. Although mild, individuals who are HSV positive have been found to have lower IQ scores, although still in the average range, and lower overall performance on broad neuro psych batteries. Several studies have also found an increased risk for Alzheimer’s disease.

Question 122

Autoimmune and paraneoplastic encephalitis

Answer 122

autoimmune encephalitis is an autoimmune syndrome associated with an attack of antibodies on neuronal cell surface or synaptic receptors that can occur with or without a cancer association. When there is a cancer association, it is classified as a paraneoplastic neurologic disorder and in many cases, symptoms of the associated encephalitis often precede the diagnosis of cancer.

Neuropathology: autoimmune encephalitis is often classified into two groups:

• -intracellular antibody disorders: paraneoplastic disorders generally fall into this group and the underlying disease mechanism seems to be an autoimmune reaction that is initiated in response to the tumor, which expresses neuronal antigens and is mediated by cytotoxic T cell responses. Paraneoplastic limbic encephalitis involves an inflammatory process related to cancers (small cell lung is most common) and localized to structure limbic system. They can be associated with specific anti syndromes (anti-Hu, anti-Yo, anti-Ri, and anti-CV2 antibodies).
• -Synaptic and neuronal surface autoantibody disorders 16 are known with syndromes classified based on the target antigen (e.g., N-methyl-D-aspartate, NMDA, GABA, glycine receptors, etc). Antibody is disrupt the neuronal receptor or synaptic protein and prevent the postsynaptic electrical impulse causing the nerve cell and brain to stop working as it should.

Anti-NMDA receptor encephalitis is one of the most common autoimmune encephalitis, second only to ADEM. It involves antibodies that decrease the number of cell surface NMDA receptors and NMDA receptor clusters in postsynaptic dendrites. NMDA receptors are highly concentrated in the hippocampus as well as the forebrain and other parts of limbic system and to a lesser extent, the frontal cortex. They play a primary role in synaptic excitatory transmission (glutamate). this can be associated with tumors (~ 50% of females over age 18 with this disease have ovarian teratomas, while only 15% of females under 14 years do; carcinomas are seen in older men and women) but this is not always the case.

Paraneoplastic disorders are relatively rare and more often occur in older adults. While anti NMDARE occurs across the age span (23 months to 76 years with a median of 19 years) other antibody associated encephalitis aids occur only in adults. Gender this varies by the type. And MD ARE is 80% more common in females. ovarian teratomas occur more often in African American patients with anti NMDARE Dan and white patients.

Mortality rates vary with paraneoplastic being higher. estimates for auto immune encephalitis are around 6%, but some studies have shown higher rates in specific subgroups. Although variable, these are associated with significant morbidity, including secondary seizures, infections, and cognitive deficits. Rates vary based on associated cancer, specific antibody involvement, and access/response to treatment.

NP:
IQ generally average longterm. In kids: improves over time, but 1/3 show impairments acutely with most improving to the broad average range >12 mo after onset. Poor academic performance noted at follow-up in 36% of small peds sample.
Attn: Attention and working memory deficits are seen at all points of recovery.
PS: although it improves with time, deficits processing speed just for some.
Language: Not consistently found to be impaired and adolescents or young adults. In kids, language problems (mutism) are often part of symptom presentation, but are generally intact at follow-up period verbal fluency impairments persist for a small percentage long term.
Visuospatial: Visual spatial skills are worse. This improves at follow up. For kids, visual motor integration is impaired in about 8 third of patients initially but most are average at follow up.
Memory: episodic memory is considered a core deficit, 55% of patients. inability to consolidate new memories is often last to recover. Verbal memory generally is more affected, though visual memory impairment has also been reported.
EF: Persistent cognitive deficits are seen in executive functions in 50% of patients
Emotion/Personality: little data. in adults, higher levels of anxiety have been reported but not depression. In kids, 88% present with behavior and personality changes, but substantial or full recovery at follow-up.
Social: may see impairments

Worse outcomes in delayed initiation of immunotherapy or ineffective immunotherapy. In anti-NMDARE, age, gender, and MRI/EEG abnormality are not associated with cognitive outcomes, but surgical removal of associated tumor is associated with better outcomes and decreased risk for relapse. Presence of seizures during acute phase is associated with greater risk for development of seizures later but not with cognitive outcomes. Paraneoplastic limbic encephalitis results in sleep disturbance, impairments of cognition- most notably antero grade amnesia -and psychiatric symptoms, such as depression, anxiety, agitation, and even hallucinations. The presenting symptoms of PLE often have a sub acute onset of days or up to 12 weeks. Both HSV and various autoimmune encephalitis tides affect the limbic system and have similar clinical characteristics.

Phases of Anti-NMDARE classically involves several phases, but varies by age. The presentation in 70% of adult patients involves:
-prodromal phase includes flu like illness with fever, malaise, headache, and fatigue, which lasts 5 to 14 days.
-Psychotic phase where patients may initially present to psychiatrists or are admitted to psychiatric units with a diagnosis of acute psychosis or schizophrenia.
-Unresponsive phase where patient stop following verbal commands, appear mute or akinetic, and may have a fixed gaze. Stereotyped athetotic movements and dyskinesia’s can also occur.
-hyperkinetic phase is characterized by autonomic instability (hypo/hypertension, cardiac arrhythmia, and hypoventilation) though this is less common in children.
Children with this more commonly present with behavioral changes, such as agitation, aggression, hyperactivity, and temper tantrums do, at least in part, to psychiatric symptoms being difficult to identify in young children. Speech, personality, and sleep changes are also more often seen in children along with movement disorders.

Assessment includes labs/lumbar puncture, neuro imaging, EEG (Macy hill or generalized slowing and occasional epileptiform activity primarily in temporal lobes is seeing an anti-NMDARE and other encephalitides. In anti-NMDARE, patterns often return to normal a few months after disease onset.

Treatment: Cancer treatment. Target antibodies—first line treatment is IVIg and steroids. Plasmapheresis is generally less perfective in reducing CNS antibodies. Second line treatment is immune suppression and this is used in those with minimal response to initial treatment

Recovery: in limbic encephalitis, seizures and behavioral issues often improve rapidly with treatment, but persistent deficits are seen in memory and new learning. And anti-NMDARE encephalitis, recovery is generally slow and can take up to 18 months, and patients are often hospitalized for several months; many go to rehab hospital or even a psychiatric floor. Most of these patients 50 to 90% will show residual cognitive deficits at follow up. And 20 to 25% of patients relapse and those without a tumor and no initiation of immunotherapy are most at risk.