Category Archives: J-O

Nutritional Deficiencies

Some Common Nutritional Deficiencies

  • Korsakoff’s Disease – related to thiamine deficiency
  • Folic acid/folate deficiency – implicated in a progressive condition of mental deterioration with concomitant cerebral atrophy. It is also implicated in spina bifida/neural tube defects.
  • Vitamin deficiencies – affect anorexic young women (who show subtle neuropsychological deficits), and in the elderly (whose intake of nutrients falls below recommended standards) who show similar deficits. In the elderly undernourishment with regard to vitamins B12, B6, and folate may occur.
  • Malabsorption of vitamins, fats and other critical substances – usually related to starvation, gastrectomy, gastric bypass surgery and inflammatory bowel disease leads to neuropathies.
  • Niacin deficiency – pellagra (dementia, dermatitis, diarrhea – the three D’s)
  • Combined System Disease (pernicious anemia, or B12 deficiency) – causes a neuropathy overshadowed by spinal cord impairment.
  • Fat-soluble vitamin deficiencies and clinical signs
    • Vitamin A – Night blindness, hyperkeratosis, skin changes
    • Vitamin D – Hypocalcemia, osteomalacia, rickets, hypophosphatemia
    • Vitamin E – Neuropathy, hemolytic anemia
    • Vitamin K – Prolongation of prothrombin time, easy bruising
  • Alcohol provides 7 kcal/g, but lacks in vitamins and minerals, can result in Wernicke’s encephalopathy and macrocytic anemia, respectively. Patients who do not respond to oral supplements may require subcutaneous injections of vitamins. If a diuretic is being taken, serum potassium, zinc and magnesium levels should be closely monitored.

Sources of Vitamins and Minerals

  • Thiamine (Vitamin B1)
    • Found abundantly in all varieties of food stuffs and is rapidly destroyed with cooking. Deficiency occurs in alcoholics, patients undergoing peritoneal dialysis, long administration of Glucose. Deficiency symptoms can be “Tingling and numbness” of fingers and toes.
  • Riboflavin (Vitamin B2)
    • Found in milk, meat, fish, leafy vegetables and is also destroyed with cooking. Deficiency causes sore mouth, apthous ulcers, anaemia.
  • Niacin (Vitamin B5)
    • Found in whole grain cereals, nuts, fish, meat. Deficiency can be associated with a high intake of maize. Symptoms are rapid loss of weight, diarrhea, fatigue and sometimes even severe loss of memory (dementia).
  • Pyridoxin (Vitamin B6)
    • Found in meat, vegetables, whole grain cereals. Deficiency can occur in alcoholics, pregnancy, intake of certain drugs like Isoniazid (Anti T.B. drug), oral contraceptives. Symptoms of deficiency are Seborrhoeic dermatitis ( a dandruff-like condition of scalp, eyebrows), cuts on the lips (Chelitis), burning sensation of the tongue, tingling and numbness of hands and legs.
  • Cobalamine (Vitamin B12)
    • Found in kidney, eggs and milk. Cobalamin is an essential intrinsic factor required for the formation of Hemoglobin.
    • Deficiency can be found in patients with impaired gastric absorption, pancreatic diseases. Symptoms are anaemia, low B.P., tingling and numbness of extremities, redness and burning of tongue (glossitis).
  • Vitamin C (Ascorbic Acid)
    • Found in fresh vegetables , citrus fruits. Deficiency can cause bleeding gums, delayed healing of colds, Pupura (bleeding disorder).
  • Folic Acid
    • Found in green, leafy vegetables. Defective absorption in cases with chronic gastric problem can lead to deficiency. Also in patients undergoing Dialysis, Hyperthyroidism, pregnancy. Deficiency symptoms include Megaloblastic Anaemia, Glossitis, Chelitis.
  • Vitamin A
    • Found in animal food, carrot etc. Deficiency causes dryness of eyes and skin, night blindness, corneal ulcers.
  • Vitamin D
    • Found in milk, fish, eggs, butter. Inadequate exposure to sunlight also can cause deficiency.In children it causes rickets and Osteomalacia (softening of bones) in adults, muscle weakness and muscular cramps.

Additional Resources

The following web sites are also useful resources.

http://apps.medsch.ucla.edu/nutrition/nutritdef.htm

http://apps.medsch.ucla.edu/nutrition/nutritpath.htm

Nonverbal Skills

Definitions

Visual-perceptual

Form or pattern discrimination; color, shape, features of object regardless of location

Visual-spatial

Processing of visual orientation or location in space; depth, motion

  • “Types” of visual-spatial processes
    • Object localization- ability of any sensory system to locate object in space
    • Line orientation- human cortex has detectors of line orientation; damage to right posterior disrupts this function, regardless of sensory modality
    • Spatial synthesis- perceived spatial features of an object that make it “that object”
    • Spatial attention- ability to pay attention to either right or left hemispace; contralateral parietal lobe
    • Spatial mental operations- mental rotation (imagining an object if displace along a line); mental reflection (imagining an object reflected in a mirror)

Constructional ability (constructional praxis)

Ability to draw or assemble an object from component parts

  • Integrative aspect- people with deficits may be able to reproduce components of design but not integrated whole
  • on command or copying

Memory

  • Spatial memory- short term; long term; discrete lesion (right hippocampus; thalamic mesiodorsal nucleus) can cause memory deficits with preservation of spatial perception
  • Topographical memory- find way around; relies on landmark recognition, spatial attention, spatial memory

Development of Skills

Visual-spatial skills

Development of locomotion essential to development of visual-spatial skills

  • Once child walks or crawls, changes way view space and increases strategies to solve spatial problems
  • When infant allowed to move independently rather than being carried by others, has better grasp of spatial features
  • Research shows strong correlation between self-produced movement and visual tracking

Verbal Representation of Visual-Spatial Concepts

Consistent developmental picture across languages in comprehension and elicitation

  • In, on , under, next to
  • Between, in back of, in front of (using a featured object¬)
  • In back of, in front of (using a nonfeatured object)

Construction of 3-D Objects

  • “Small scale models”- using everyday objects to represent other things (ex- pretend chair is a stove; long, flat block could be road or house depending on orientation)
  • Uni-dimensional representation- forms are linear; house may be stack of blocks, but each block stands for a feature
  • Two-dimensional representation- starts creating overall shape with blocks; begin to overlook boundaries of blocks and depict surface of object; uneven block on top for chimney
  • Three-dimensional representation- building on all three axes; positions blocks so many facets join other blocks; builds interior vacant space

Drawing

  • Interest in crayons; making marks
  • Point-plot representations- spatial plotting of features of an object; features not contoured or connected
  • Beginning figure-ground relationship- more visual-spatial likeness of object (long strokes for hair)
  • Three dimensional space- scenes with figures side by side

Neuroanatomy

Right Hemisphere

  • More white matter; less gray matter
  • More associative cortex
  • More interconnections
  • Advantage for processing complex information; many modes within an single task
  • Configurational processing; material that cannot be described adequately as a string of symbols (faces, 3D objects)
  • Preference for global aspects
  • Involvement in language- integration of relationships in verbal/written discourse; integrating verbal output; making verbal expression appropriate for context/emotion; humor; alternative meanings; intonation; prosody

Anterior Parietal Lobe

  • somatosensory cortex
  • involved with somatic sensation and perception

Posterior Parietal Lobe

  • inferior posterior lobule- high order somatosensory and visual cortical fields
  • superior posterior lobule- somatosensory association cortex
  • integrating discrete elements into whole
  • spatial, constructional, topographical skills

Where vs. What Streams

  • Dorsal Visual Stream- “where”; info regarding spatial analysis and orientation; runs along top side of cerebrum from occipital to parietal visual areas
  • Ventral Visual Stream- “what”; info regarding shape, pattern; runs along underside of cerebrum from occipital to temporal visual areas

Temporal Lobe

Nonverbal analogues of left hemisphere

  • nonverbal sound discrimination, recognition, comprehension
  • visual, auditory, tactile memory (faces, designs, melodies)
  • anterior- storage; posterior- retrieval

Tests

Visual attention

  • Cancellations tasks
  • Line bisection
  • Picture description- ask describe what in picture or count certain object in picture
  • Reading- omit part of line
  • Written expression- copy sentences

Visual recognition

  • JLO
  • Recognize objects under distorted conditions
  • Facial recognition
  • Discriminate rotations of objects
  • Visual organization; incomplete figures
  • Fragmented visual stimuli (Hooper)
  • Ambiguous stimuli

Constructional skills

  • Drawing tasks (VMI, Rey; copy vs free draw)
  • Building tasks

Memory

  • Visual recognition
  • Visual reproduction
  • Visual learning

Disorders

Visual Agnosia

  • Inability to recognize object
    • Associative- person can still draw or describe major details of stimuli
    • Apperceptive- person cannot draw or match visual stimuli
  • Agnosia vs anomia- if person can still describe what object is and what used for (only a naming deficit) then it is anomia

Prosopagnosia

  • Inability to recognize previously known faces and learn new ones
  • Applied to any visually ambiguous stimuli (ex. farmer not being able to recognize cows)
  • Can perform generic recognition (say that a car is a car) but no specific membership (can’t say which manufacturer of car)
  • Intact emotional recognition

Facial Processing

  • Inability to recognize facial emotion- bilateral amygdala damage
  • Deficit in social judgment of faces (judge as approachable and trustworthy)- amygdala

Simultanagnosia

  • Inability to comprehend overall meaning of stimulus- can identify and describe isolated elements
  • Can see parts, but not the whole
  • Example- person looking at eyeglasses, says there’s a circle, another circle, stick and cross bar, concludes it must be a bicycle
  • Difficulty understanding meaning of complex thematic pictures or seeing card combinations of a “hand” although know relative value of cards

Pure Alexia

  • Word blindness- impaired ability to read single words or sentences
  • Can copy them, normal visual acuity, normal recognition of nonverbal stimuli
  • Lesion that disconnects language-related temporo-parietal cortex from visual association area

Disorders of Location and Orientation

  • Deficits-inability to locate a building, find one’s room, describe either verbally or by map how to get someplace
  • Can be caused by neglect or impairment of visuospatial memory- can no longer conjure up previously stored memories to get bearings and establish route
  • Bilateral posterior lesions

Unilateral Spatial Neglect

  • Tendency to neglect one-half of extrapersonal space- integrated disorder of attention and vision
  • Tests involve having person draw a symmetrical picture (clock, flower).
  • Neglect occurs contralateral to the brain lesion.
  • Most often in acute phase of recovery.
  • Seen with more frequency and severity after right hemisphere than left hemisphere lesions.
  • Also seen following lesions of cortical and subcortical parietal lobe, dorsolateral frontal lobe, cingulated gyrus, thalamus, and reticular formation.

Balint’s Syndrome

  • Disorder of spatial analysis
  • “Acquired disturbance of ability to perceive the visual field as a while, resulting in unpredictable perception and recognition of only parts (simultanagnosia) which is accompanied by impairment of target pointing under visual guidance (optic ataxia) and inability to shift gaze at will toward new visual stimuli (ocular apraxia)”
  • Three major components-
    • Visual disorientation (simultanagnosia)
    • Optic ataxia (deficit of visually guided reaching)
    • Ocular apraxia (deficit of visual scanning)
  • Visual disorientation is core. Person only able to grasp fraction of visual field, and this fragment is not stable and moves erratically. As a result, objects disappear from view, so can’t describe more than one or two parts of an object. Also fail to orient to new stimuli unless happens to be in window of vision
  • Optic ataxia- person can point to parts of body, garments, sound, but not to visual stimuli
  • Ocular apraxia- cannot direct gaze voluntarily toward new stimulus. Normally, person produces a quick saccade toward something new. Can’t do this, even if told something is there.
  • Bilateral damage to occipitotemporal region

Constructional Apraxia

  • “apraxia of the psychologist”- seen more in evals than in real life
  • inability to assemble, join, or articulate parts in a unitary structure.
  • parietal dysfunction, usually right
  • Drawing- left hemisphere damage leads to drawing that is spatially correct, but oversimplified with omission of details
  • Drawing- right hemisphere damage leads to fragmented drawing; may have details but lost whole of picture and spatial relations; may neglect left side
  • Block constructions- left hemisphere damage see maintenance of 2×2 or 2×3 configuration but error with internal details; tend to recognize when incorrect
  • Block construction- right hemisphere damage break configuration, but see internal details; do not appreciate when incorrect; may skew to right space

Disorders Demonstrating Deficits in Nonverbal Abilities

  • Syndromes
    • Velocardiofacial syndrome
    • Williams syndrome
    • deLange syndrome
    • Sotos syndrome
    • Turner syndrome
  • Anomalies of brain or CNS
    • hydrocephalus
    • spina bifida
    • congenital hypothyroidism (insufficient production of thyroid hormones; this hormone facilitates glial cell production)
    • MS
    • Metachromatic leukodystrophy

Hydrocephalus

  • Increase in CSF volume in ventricular system
  • Can result from structural abnormality blocking CSF outflow (Arnold Chiari)
  • Children with IVH can develop as a result of blockage of CSF reabsorption
  • Also associated with TBI, infectious diseases, tumor
  • Classified three ways
    • Complicated (associated with other clinical problems) or noncomplicated
    • Communicating (obstruction occurs in subarachnoid spaces, where CSF is blocked as it leaved fourth vent) or noncommunicating (obstruction within vent system)
    • Congenital or postnatal
  • Consequences on brain development
    • Stretch or destroy CC
    • Affects white matter tracts, especially projection fibers near midline
    • Disrupt myelination, resulting in reduced cortical mantel, reduced brain mass, and thinning of posterior brain regions.
    • Multiple surgeries to correct shunt
  • Neuropsych
    • PIQ < VIQ
    • visual-spatial/ visual-motor < language
    • some studies kids with shunts did worse
    • some language probs: rapid retrieval of info; automaticity; language discourse; cocktail party speech
    • deficits in both verbal and visual memory
    • executive deficits
    • Studies show relationship between size of corpus callosum and nonverbal skills

ALL

  • cancer of blood-forming cells in bone marrow; peak incidence 3-5 yrs of age
  • strikes when CNS highly vulnerable to insult
  • treatment goal is total eradication of disease; 95% chance of remission; > 50% chance of remission for 5 years.
  • treatments are bad for CNS: radiation, intrathecal chemo, steroids
    • cortical atrophy; lead to ventricular or subarachnoid space dilation
    • leukoencephalopathy: myelin degeneration; white matter of both hemispheres; watershed areas
    • mineralizing microangiopathy :degeneration of microvasculature; dystrophic calcifications of adjacent areas; CNS calcifications of gray matter, primarily around BG
  • Neuropsych deficits are late effects
    • 10 pt IQ drop
    • nonverbal < verbal; arithmetic < reading
    • nonverbal memory < verbal memory
    • attention problems; difficulty focusing and planning responses
    • executive deficits
    • diminished response time and motor speed
  • Risk factors associated with treatment effects
    • Age: myelin still developing; < 5 is bad
    • Gender: impairment more prevalent and severe in females; females more vulnerable to radiation/methotrexate combo (males may be more vulnerable to steroids)
    • Treatment: combo of radiation and intrathecal methotrexate worse than just XRT. XRT dose > 2000 cGy and higher MTX associated with leukoencephalopathy
    • Sequence of treatment: lower CNS pathology when IT MTX given before XRT rather than after. Hypothesized that radiation affects integrity of BBB, allowing increased penetration of MTX and reduced clearance of MTX from brain.

TBI

  • Primary injury: coup/contrecoup; contusions and hemorrhages
  • Secondary injury: edema, hematoma, seizure; major causes of tissue loss
  • Late effects: white matter degeneration; cerebral atrophy; ventricular enlargement
  • White matter degeneration primary pathological change in brain. As edema resolves, reduction in myelin, resulting in reduced bulk of cerebral white matter. Damage greatest in CC, parasaggital areas, internal capsules, and pons.
  • Neurospych
    • Decline in IQ
    • PIQ more affected because of task demands, which require fluid problem solving and rapid motor output vs previously acquired info, which remains relatively intact
    • after acute stage, language skills relatively intact; can see subtle problem with naming and fluency and discourse
    • deficits in both verbal and visual memory
    • deficits in attention and executive skills

Nonverbal LD

  • Rourke- Final Common Pathway of White Matter
  • Syndrome or cluster of features related to dysfunction of white matter; processing multi-modal novel info and spatial info
  • Three areas of deficits
    • neuropsychological
    • academic
    • social-emotional
  • Where does it fit in as a syndrome?
  • What criteria are used to diagnose?
  • Overlap with NLD and Asperger’s- differential diagnosis
    • NLD- neuropsych exam important
    • AD- more of a behavioral diagnosis; looking for more social-emotional problems, behavioral rigidity, restricted interests
  • Overlap with ADHD- social problems related to impulsivity

Neurotransmitters and Drugs of Abuse

Dopamine

Synthesis and Metabolism

Phenylalanine —> Tyrosine —> DOPA —> Dopamine (DA)

Anatomy

  • Synthesized mainly in neurons located in the ventral midbrain (substantia nigra pars compacta & ventral tegmental area)
  • Three projection systems:
    • Nigrostriatal Pathway: Substantia nigra to caudate and putamen (implicated in Parkinson’s)
    • Mesolimbic Pathway: Midbrain to limbic structures (implicated in positive symptoms of psychosis)
    • Mesocortical Pathway: Midbrain to prefrontal cortex (implicated in working memory and other executive skills and cognitive deficits and negative symptoms of Schizophrenia)

Conditions Due to Deficits in Dopamine Synthesis

Phenylketonuria (PKU)

  • Inherited disorder of enzyme that breaks down phenylalanine into tryrosine
  • Results in excessive phenylalanine (excreted in urine) and dopamine depletion
  • If not put on very low phenylalanine diet, the individual will develop mental retardation. Even on diet, executive functioning deficits occur.

Parkinson’s Disease

  • Deficit in conversion of precursors into DOPA, which results in diminished DA
  • Involuntary movement disorder with both “positive symptoms” (e.g., tremor, especially when on L-Dopa), and “negative symptoms” (e.g., bradyphrenia, bradykinesia)
  • Treated with L-Dopa (which boosts DOPA levels), drugs that reduce L-Dopa metabolism outside of the CNS (which allows for lower L-Dopa doses and fewer systemic side effects), or DA agonists

Conditions Due to Excessive Dopamine Activity

Synthetic Causes

  • Excessive L-dopa
  • Cocaine
  • Amphetamines

Endogenous Causes

  • Tardive Dyskinesia Probable increased DA sensitivity due to antipsychotics. Results in visual hallucinations, psychosis, hyperkinetic movement disorders (e.g., dystonia, chorea)

Norepinephrine (NA) and Epinephrine

(norepinephrine is also known as noradrenaline)

Synthesis and Metabolism

Dopamine —> Norepinephrine —> Epinephrine

Anatomy

  • NA synthesized primarily in locus ceruleus (located near fourth ventricle in the rostral/dorsal pons)
  • Projects to the entire forebrain through the thalamus
  • Ascending norepinephrine projection system implicated in modulation of attention, sleep-wake states, mood
  • Epinephrine synthesized in adrenal gland
  • Outside CNS, major neurotransmitters in the sympathetic nervous system

Related Disorders

  • ADHD: Psychostimulant or SNRI (Strattera) treatment enhances noradrenergic transmission and/or reduces reuptake
  • Neuronal depletion of locus ceruleus in Parkinson’s can lead to depression and sleep disorders
  • Noradrenergic transmission also seems to be important in mood disorders including depression and bipolar and anxiety disorders
  • NA depletion can result in orthostatic hypotension and other symptoms of reduced sympathetic n. system activity
  • Excessive NA causes tremor, sympathetic nervous system overactivity (e.g., bronchodilation, arterial dilation)

Serotonin

Synthesis and Metabolism

Tryptophan —> 5-Hydrotryptophan —> Serotonin (5-Hydrotryptamine or 5-HT)

Anatomy

  • Synthesized in dorsal raphe nuclei of the midbrain and pons
  • Projects to entire forebrain including cortex, thalamus, and basal ganglia
  • Many different receptor types result in a variety of symptoms/behaviors associated with 5-HT disorders

Related Disorders

  • Low 5-HT> depression, anxiety, OCD. Also found in Parkinson’s (esp. if depressed) and Alzheimer’s
  • Excessive 5-HT> LSD and Ecstasy are serotonin agonists that cause psychosis and hallucinations

Acetylcholine

Synthesis and Metabolism

Acetyl CoA + Choline —> Acetylcholine (ACh)

Anatomy

  • Synthesized mainly in nucleus basalis of Meynert and adjacent nuclei in the basal forebrain
  • Two kinds of receptors:
    • Nicotinic: Involved almost exclusively at neuromuscular junction
    • Muscarinic: Involved in cerebral cortex (especially in arousal and memory functioning)

Related Disorders

  • Alzheimer’s Disease: Deterioration of nucleus basalis of Meynert implicated in memory dysfunction. Anticholinesterases (e.g., Cognex, Aricept) show some effectiveness in slowing progression a bit.
  • Botox inhibits Ach release from presynaptic neuron, resulting in localized loss of muscle tone
  • Neuroleptics can cause anticholinergic side effects (e.g., confusion, drowsiness, dry mouth); those that tend to produce the least extrapyramidal symptoms (see DA, above) tend to have more anticholinergic side effects.

Glutamate

Synthesis and Metabolism

Glutamine —> Glutamate

Anatomy

  • Major excitatory amino acid; NMDA receptor modulates Calcium channel flow
  • Projects throughout central nervous system

Related Disorders

  • Excessive Glutamate: Causes excitotoxicity, a probable cause of cell death in TBI, stroke, other disorders.

Gamma-Aminobutyric Acid (GABA)

Synthesis and Metabolism

Glutamine —> GABA

Anatomy

  • Major inhibitory transmitter; opens Chloride (Cl-) channels and closes Calcium channels, hyperpolarizing cells
  • Widespread in entire central nervous system, but highest in striatum, hypothalamus, spinal cord, and temporal lobes.

Related Disorders

  • GABA Deficiency: Implicated in epilepsy and, sometimes, chorea
  • Many antiepileptic medications increase GABA activity

Several Drugs of Abuse

(not including alcohol)

Cocaine

Pharmacology

  • CNS Stimulant
  • Blocks re-uptake of DA, NA, and serotonin, while also causing release of DA into synaptic cleft

Desired Effects

  • Euphoria
  • Increased vigilance

Overdose

  • Agitation, paranoia, delusions, hallucinations
  • Strokes (or heart attacks) and seizures
  • Long-term use: involuntary movement disorders (e.g., “crack dancing”: inability to stand still)

Withdrawal

  • Emotional “crash”: dysphoria, anhedonia, strong craving for drug
  • Rebound of REM sleep (which was suppressed while on drug), resulting in vivid, disturbing dreams

Amphetamine

Pharmacology

  • CNS Stimulant, lasting much longer than cocaine
  • Blocks re-uptake of DA while also causing release of DA into synaptic cleft

Desired Effects

  • Euphoria
  • Increased vigilance (many ADHD drugs are amphetamines or amphetamine-like)

Overdose

  • Paranoia, delusions, hallucinations
  • Strokes (or heart attacks) and seizures
  • Long-term use: involuntary movement disorders

Withdrawal

  • Emotional “crash”: dysphoria, anhedonia, strong craving for drug
  • Rebound of REM sleep (which was suppressed while on drug), resulting in vivid, disturbing dreams

Opioids

Pharmacology

  • Can affect DA and other neurotransmitters, but primary effect at opiate receptors

Desired Effects

  • Pain reduction
  • Anxiety reduction
  • Sleepiness

Overdose

  • Coma, “pin-point pupils” (miosis), and respiratory depression
  • Cerebral hypoxia
  • Rarely associated with seizures or cerebral hemorrhages

Withdrawal

  • Strong craving for drug
  • Dysphoria, autonomic hyperactivity

PCP (Phencyclidine)

Pharmacology

  • Central analgesic, depressant, and hallucinogen
  • Blocks re-uptake of DA, NA, and serotonin, prevents glutamate from activating NMDA receptor

Desired Effects

  • Low doses like alcohol use
  • Higher doses cause both positive and negative symptoms of schizophrenia

Overdose

  • Muscle rigidity, vertical nystagmus, stereotypies, blank stare, unresponsiveness
  • Seizures that can lead to status epilepticus
  • Violent, psychotic behavior

Marijuana

(especially the THC in it)

Pharmacology

  • Affects THC receptors in cortex, basal ganglia, hippocampus, and cerebellum

Desired Effects

  • Calming
  • Reduced nausea or vomiting
  • Mood elevation

Negative Effects

  • Slowed mentation
  • Sedation
  • Sometimes hallucinations at high doses
  • Sometimes lasting inattention
  • Fluency problems
  • Impaired executive functioning

Neurologic Exam

Mental Status

  • Level of Alertness, Attention, and Cooperation:
    • Can use test of working memory and attention (e.g., digit span; w-o-r-l-d/d-l-r-o-w)
    • What is being tested? Altered consciousness can stem from:
      • Damage to brainstem reticular formation
      • Bilateral lesions of the thalami or cerebral hemispheres
      • Can be mildly impaired in unilateral cortical or thalamic lesions
      • Toxic or metabolic factors may lead to impaired consciousness b/c of their effects on these structures
  • Orientation
  • Memory
    • Tests e.g.’s include asking patient to recall 3 items or a brief story for a delay of 3-5 minutes and can evaluate patient’s memory about own history
    • What is being tested?
      • Problems with immediate memory more likely related to attention
      • Difficulties recalling info after 1-5 minutes may implicate the limbic memory structures in the medial temporal lobes and the medial diencephalon
  • Language
  • Spontaneous speech – observe fluency, phrase length, and abundance of spontaneous speech; observe for paraphasic errors, neologisms, or grammatical errors
  • Comprehension
  • Naming
  • Repetition
  • Reading
  • Writing
  • Gerstmann’s Syndrome
    • Deficits in calculations, right-left confusion, finger agnosia and agraphia
    • Deficits in all 4 areas implicate the dominant parietal lobe
  • Apraxia:Inability to follow a motor command that is not due to a primary motor deficit or language impairment
  • Implicates language areas and adjacent structures of the dominant hemisphere
  • Neglect and Constructions
    • Extinction on double simultaneous stimulation – patients can detect stimulus affected side when presented alone, but when stimuli are presented simultaneously on both sides, only the stimulus on the unaffected side may be detected
    • Anosognosia – unawareness of deficits on the affected side of their body
    • What is being tested?
      • Hemineglect is most common in lesions of the nondominant parietal lobes
      • Can occasionally be seen in right frontal lesions, right thalamic or basal ganglia lesions and rarely in lesions of the right midbrain.
      • In left parietal lesions, a much milder neglect can be seen affecting the patient’s right side
  • Sequencing Tasks and Frontal Release Signs Evaluating for signs of frontal lobe damage such as:
  • Perseveration
  • Motor impersistence – a form of distractibility in which patients only briefly sustain a motor action in response to a command such as “raise your arms”
  • Auditory go-no-go test
  • Frontal release signs – e.g., grasp reflexes
  • Changes in personality and judgment
  • Logic and Abstraction
  • Delusions and Hallucinations
    • Can be seen in toxic or metabolic abnormalities and other causes of diffuse brain dysfunction as well as in primary psychiatric disorders
    • Abnormal sensory phenomena can also be caused by focal lesions or seizures
  • Mood

Cranial Nerves

  • Olfaction (CN I)
    • Not often tested unless specific pathology such as subfrontal tumor is suspected
    • Do not use noxious orders as they may stimulate pain fibers from CN V.
  • Opthalmoscopic Exam (CN II)
    • Allows direct visualization of damage to retina, optic nerve atrophic changes, papilledema and other important abnormalities
  • Vision (CN II) check for:
    • Visual acuity
    • Color vision (red desaturation is a sign of subtle asymmetry in optic nerve function)
    • Visual fields
    • Visual extinction
    • What is being tested?
      • Lesions in front of the optic chiasm (eye, optic nerve_ cause visual deficits in one eye while lesions behind the optic chiasm (optic tract, thalamus, white matter, visual cortex_ cause visual field deficits similar for both eyes
  • Pupillary Responses (CN II, III)

see p. 59 for full details

  • Extraocular Movements (CN III. IV, VI)
    • checked by having patient moving eyes without moving their head
    • Test for smooth pursuit by having a patient follow a moving object
    • Test convergent movements – does patient demonstrate a dysconjugate gaze (eyes not fixated on same point) – results in diplopia(double vision)
    • Saccades – eye movements used to rapidly fixate from one object to another (look at my thumb, look at my finger)
    • Optokinetic nystagmus – abnormalities in smooth pursuit eye movements

Motor Exam

Only relevant info is detailed here – for full review see pages 63-70

  • Observation
    • Observe for sings of involuntary movements and tremors – associated with lesions in ganglia or cerebellum (tremors can also occasionally be seen in peripheral nerve lesions)
  • Muscle Tone Testing

Evaluates for resistance or rigidity by asking patient to relax and then passively move each limb- helps to distinguish between upper motor neuron and lower motor neuron lesions

  • Signs of lower motor neuron lesions – weakness, atrophy, hyporeflexia (reduced reflexes)
  • Signs of upper motor neuron lesions – weakness, hyperreflexia, and increased tone.
    • In acute upper motor neuron lesions, there is often flaccid paralysis with decreased tone and reflexes; over time (hours to weeks) increased tone and hyperreflexia usually develop
  • Increased tone can also occur in basal ganglia dysfunction
  • Slow or awkward finger movements or toe tapping in the absence of weakness can signify an abnormality in the corticospinal pathways, but can also occur in lesions of the basal ganglia or cerebellum
  • Reflexes
  • Plantar Response – tested by scraping an object across the sole of the foot…
    • Normal response is downward contraction of the toes
    • Abnormal response – Babinski sign – is characterized by an upgoing big toe and fanning outward of the other toes. Toes that do not move up or down (called “silent”) are also considered abnormal.
  1. 1Abnormal in all adults, although present in infants up to the age of about 1 year
  2. 2Where localized? Upper motor neuron lesions anywhere along the corticospinal tract
  • Frontal release signs – reflexes normally present in infants but that are pathological in adults (from frontal lobe lesions)
    • These include the grasp, snout, root and suck reflexes

Coordination and Gait

Re: disturbances of coordination and gait can be caused by lesions in many other systems other than the cerebellum

  • Ataxia – abnormal movements seen in coordination disorders;
    • Overshoot is commonly seen and is sometimes referred to as past pointing
  • Dysdiadochokinesia – abnormal alternating movements
  • Appendicular ataxia – affects movements of extremities and is usually caused by lesions of the cerebellar hemispheres and associated pathways
    • Can be tested by having patient complete rapid alternating movements, finger-nose-finger test, or heel-shin test
  • Truncal Ataxia affects proximal musculature, especially that are involved in gait stability, and is caused by midline damage to the cerebellar vermis and associated pathways
    • Romberg test – ask patient to stand with their feet together with eyes open and then to close their eyes – if they then sway or lose balance suggests impairment in the proprioceptive or vestibular systems
    • Can be used to implicate the midline cerebellar region (however, similar deficits can be seen with lesions in other parts of the nervous system such as upper or lower motor neurons or basal ganglia)
  • Gait
    • Evaluate patient’s tandem gait (walking in a straight line heel to toe); patients with truncal ataxia caused by damage tot he cerebellar vermis or associated pathways will have particular difficulty with this task, since they tend to have a wide-based, unsteady gait and become more unsteady when attempting to keep their feet close together.
    • Gait apraxia – rare disorder where person can carry out all movements required for gait normally when lying down – but is unable to walk in standing position; believed to be associated with frontal disorders or normal pressure hydrocephalus

Sensory System

  • Primary Sensation, Asymmetry, Sensory Level
    • Evaluates pain sensation, temperature sensation, vibration sense, joint position sense and 2-oint discrimination (see p. 71 for full details)
  • Cortical Sensation, Including Extinction

Test for:

  • Graphesthesia – can patient identify letters and numbers that are written onto their palm or fingertips
  • Stereognosis – can patient identify objects by touch
  • Tactile extinction on double simultaneous stimulation
  • Deficits in these domains can be due to lesions in peripheral nerves, nerve roots, posterior columns or anterolateral sensory systems in spinal cord or brainstem, thalamus, or sensory cortex

Coma Exam

Please refer to pages 73 – 78 for full review

  • Conditions that can be mistaken for coma:
    • Large lesions involving frontal lobes or their connections can cause a condition resembling coma called akinesia or abulia – in this state patient has profoundly decreased initiative and minimal responsiveness, but the eyes are usually open and there may be occasional normal-appearing movements
    • Catatonia
    • Locked-in syndrome – consciousness and sensation may be normal, but the patient is unable to move because of a lesion in the brainstem motor pathways or because of peripheral neuromuscular blockade

Neuropsych Aspects of Psychopathology

Schizophrenia

Brief History

  • Kraeplin (1919) came up with first definition (called it dementia praecox)
  • Blueler (1950) introduced the term “schizophrenia” (Bleuler’s 4 A’s: Association, Affect, Ambivalence, and Autism)
  • Schneider (1959) came up with 11 pathognomonic symptoms (Schneiderian First Rank Symptoms)
  • Crow (1980) proposed that schizophrenia be divided into 2 major syndromes (Type I and Type II)
    • Type I = domination of positive symptoms (Normal brain structure, Most intact neurocognitively, Relatively good response to treatment)
    • Type II = domination of negative symptoms (Structural brain abnormalities, Impaired cognitive functioning, Poor response to treatment)

DSM-IV criteria (briefly)

  • Characteristic Symptoms (two or more)
    • delusions
    • hallucinations
    • disorganized speech
    • grossly disorganized or catatonic behavior
    • negative symptoms
  • Social/Occupational Dysfunction
    • work
    • interpersonal relationships
    • self-care
  • Duration
    • Continuous signs of the disturbance persist for at least 6 months
    • This 6-month period must include at least 1 month of symptoms (or less, if being treated)
  • Exclusion of schizoaffective and mood disorder
  • Exclusion of substance/general medical condition
  • If there is a relationship to a pervasive developmental disorder, schizophrenia is only diagnosed if prominent delusions or hallucinations are also present for at least a month

Etiology (Biological View)

  • Genetics
    • General population is 1%
    • Identical twin = 48%
    • Offspring of two schizophrenic parents = 46%
    • Fraternal twin = 17%
    • Sibling = 9%
    • Half sibling = 6%
    • First cousin = 2%
    • Adoption studies
    • Possible defects found on several chromosomes
  • Biochemical Abnormalities
    • Dopamine Hypothesis (Too much dopamine; Neuroleptics block dopamine receptors)
    • Amphetamines prevent reuptake of dopamine, and individuals on amphetamines can display symptoms of schizophrenia
  • Abnormal Brain Structure
    • Smaller frontal lobes
    • Smaller temporal lobes (decreased amygdale, hippocampus, and parahippocampal gyrus)
    • Abnormalities in the limbic system and basal ganglia
    • Enlarged ventricles (especially in Type II)
    • Smaller amounts of cortical gray matter
    • Abnormal blood flow in certain areas of the brain (especially frontal lobes)
  • Viral Problems
    • In vitro viral exposure that is activated by changes in hormones or other viruses
    • Influenza exposure
    • Pestiviruses (found in 40% of schizophrenics)
    • Higher number of schizophrenics during the winter
    • May explain why fraternal twin has a greater chance than a sibling

Neuropsychological Functioning

  • Frontal lobe dysfunction
    • Impaired attention including problems with filtering, problems distinguishing relevant from irrelevant information, selective attention is often impaired with increased information load, sustained and focused attention abilities are often poor.
    • Problems with abstraction
    • Problem solving deficits on WCST, CST
    • Poor planning on the Clock Drawing, secondary to verbally mediated planning difficulties
  • Memory deficits
    • Impaired CVLT-II, WMS-III, BVRT
    • CVLT research shows impairment in learning, recall, and recognition measures, but equal-to-normal retention of information over the delay (i.e., normal storage)
  • Can have deficits on language tests
    • In speech disordered schizophrenics (e.g., Disorganized Type), can have impaired BNT
    • On the COWA, Schizophrenics produce more phonemic responses than category words
  • Slower reaction time to both auditory and visual signal on the RT

Bipolar Disorder

DSM-IV Criteria of mania (briefly)

  • Elevated, expansive, or irritable mood lasting at least one week
  • Three or more of the following (four if mood is only irritable)
    • Inflated self-esteem or grandiosity
    • Decreased need for sleep
    • More talkative or pressured speech
    • Flight of ideas or racing thoughts
    • Distractibility
  • Increase in goal-directed activity
    • Excessive involvement in pleasurable activities that have a high potential for painful consequences
  • Significant stress or impairment
  • All typical exclusions apply (not due to other psych, medical, substance D/O, etc.)

Bipolar I Disorder vs. Bipolar II Disorder vs. Cyclothymia (briefly)

  • Bipolar I Disorder – Presence of mania and depression
  • Bipolar II Disorder – Presence of depression and hypomania (no history of manic episodes)
  • Cyclothymia – Two years of mood cycles, but events don’t meet criteria of depression or mania (less severe with shorter swings)

Etiology (Biological Model)

  • Structural brain abnormalities (ventricular enlargement)
  • Genetic factors (possible genetic links have been found on chromosomes 11 and X
    • 40% chance for MZ twin to get it
    • 5-10% chance of a close relative to get it
    • 1% chance in the general population
  • Neurotransitters
    • High norepinephrine
    • Serotonin can be implicated (low)
  • Ion Activity
    • Improper transportation of sodium and potassium ions between the outside and the inside of the neuron’s membrane

Neuropsychological Functioning

  • General intellectual function is largely preserved in BD.
  • Impairments when present are limited to acute episodes and to performance scores.
  • Abnormalities in attention are seen in symptomatic patients and persist in remission in measures of sustained attention and inhibitory control.
  • Verbal memory may be impaired even in euthymic patients, while visual memory deficits are variable depending on the tasks used.
  • Executive functioning (planning, abstract concept formation, set shifting) are impaired in symptomatic patients, but it may be normal in fully recovered patients

Obsessive Compulsive Disorder

DSM-IV Criteria (briefly)

  • Either obsessions or compulsion
  • Insight at some point (If not, then subtype “poor insight)
  • Marked distress, time consuming (>1 hour per day), or significantly impairs functioning
  • If there is another Axis I disorder, O-C are not restricted to it
  • Not due to substance use or medical disorder

Etiology (Biological Model)

  • Structural abnormalities
    • Orbital frontal cortex
    • Caudate nucleus
    • Cingulate gyrus
  • Neurochemical: Possible down-regulation in both the number of serotonin receptors and release of serotonin

Neuropsychological Functioning

  • Investigations generally agree on localization of dysfunctional areas (e.g., prefrontal and frontal regions, limbic system, basal ganglia).
  • They disagree as to hemisphere and frontal lobe side impairment, involvement of other brain areas, pathophysiological connections, and impact of developmental phases and of concomitant cognitive and affective conditions.

Neuroimaging

History

CTs developed in the 1970’s — MRIs developed in the 1980’s

Plain Film Analysis

  • Used to evaluate structures of skull, facial bones, and sinus
  • Usefulness declined with advent of CT and MRI
  • Still used in detection of fractures, abnormal calcifications, developmental abnormalities, osteolytic or osteoblastic disorders. For example
    • Identification of neoplasms
    • Premature closing (craniosynostosis or widening – from increased ICP seen in aqueductal atresia and Dandy-Walker syndrome)
  • Generally not indicated after trauma – CT should be used (although good for diagnosis of facial fractures)

Imaging Planes

  • CT and MRI imaging planes are similar to the horizontal (axial) coronal and sagittal planes used to describe basic neuroanatomy (Figure 2.5)
  • But CT axial slices are sometimes adjusted by a few degrees off the true axial plane
  • This adjustment lets radiologists get more brain with fewer slices and with less radiation exposure to eyes
  • MRI slices are usually true horizontal

Scout/localizer images – show the viewer where the image slices are (see figure 4.1). Should be included on all CT and MRI scans so exact angle can be documented and compared

Computerized Tomography (CT)

  • Developed directly from X-ray technology. Similarly it measures the density of tissue.
  • However, there are two differences from conventional x-rays:
    • Rather than taking one view, the x-ray beam is rotated around the patient to take many different views.
    • X-ray data are reconstructed by a computer to obtain detailed image including soft tissues, liquid, air and bone.

Single Slice CT

  • Scanner is shaped like large ring
  • Patient lies on table and moves through ring in small steps
  • Each stop, x-ray is scanned through patient and picked up by detectors on opposite side of ring
  • Amount of energy absorbed depends on the density of tissues traversed

Helical CT

  • Acquires data continuously as patient moves through scanner – no stops
  • Instead of single slices, up to 4 rows of detectors provide multiple overlapping slices
  • These advances greatly improved resolution and speed of CT scan (20 minutes versus 40 minutes)

Appearance of CT scans

(Review figures 4.12 [A-K] for normal CT images, also see below for comparison to MRI)

  • White – dense structures like bone
  • Black – less dense, like air
  • Hyperdense – brighter areas
  • Hypodense – darker areas
  • Grey/Isodense – intermediate density similar to brain tissue
  • Dark Grey – CSF
  • Nearly Black – fat tissue just outside skull
  • White matter is slightly darker than cellular gray matter due to high myelin content
  • Gray matter is slightly lighter than white matter due to high water content
  • Enhancing lesions may be brain neoplasms, abscess, infarct, demyelinating disease, resolving hematoma or vascular malformation

HU = Hounsfield Units – density in CT, often expressed in HU; HU = 0 for water

Hemorrhages

(see figure 5.19)

  • Depends on how recently it occurred
  • Fresh intracranial hemorrhage coagulates almost immediately and shows up as hyperdense areas relative to brain
  • As the clot is broken down, after about a week becomes isodense
  • After 2-3 weeks, become hypodense

Cerebral Infarcts

  • Acute infarcts (in first 6-12 hours) – often cannot be seen with CT
  • >12 hours, cell death and edema lead to an area of hypodensity seen in the distribution of the occluded artery
  • Over weeks to months, brain tissue surrounding infarct may shrink, producing a local area of prominent sulci or enlarged ventricles
  • Persistent areas of hypodensity in the brain tissue may be present as a result of gliosis and brain necrosis with replacement by CSF

Neoplasms

  • May appear hypodense, hyperdense, or isodense, dependant upon the type or stage
  • Intravenous contrast dye is often helpful in visualizing neoplasm

Mass Effects

  • Anything that distorts the brain’s usual anatomy – this can occur with neoplasm, edema, hemorrhage, and other conditions
  • Detected by observation of localized compression of the ventricles, effacement of sulci or distortion in other brain structures (e.g., in herniation)

Intravenous Contrast

  • Contrast material contains iodine which is denser than brain and will therefore appear hyperdense (white) in areas of increased vascularity or breakdown of blood-brain barrier
  • Often images are obtained with and without contrast for comparison
  • In suspected intracranial hemorrhage it is very important to obtain noncontrast CT because small hemorrhages often appear on CT as whitish areas at base of brain which could be masked by the normal hyperdense contrast material in blood vessels and meninges at base of brain

Myelography

  • Form of contrast enhancement
  • Iodinated contrast dye is introduced into CSF (usually by lumbar puncture)
  • Allows better visual of nerve roots and of abnormal impingement on the spinal CSF

Therapeutic Uses with CT Scans

  • Acute hemorrhage
  • Edema
  • Mass effect (although cerebellar tonsillar herniation can be missed because of beam hardening artifacts)
  • Ventricular enlargement to detect hydrocephalus
  • Detecting intracranial calcifications (from congenital infections, vascular lesions, metabolic disease, and neurocutaneous disorders)

CT versus MRI in Different Situations

Situation CT Better MRI Better
Head Trauma XX
Lower Cost XX
Subtle Tumor/Infarct XX
Brainstem Lesion XX
Fresh Hemorrhage XX
Old Hemorrhage XX
Speed Needed XX
Skull Fracture XX
Pacemaker XX
Anatomical Detail Needed XX
  • MRI provides high-contrast, high-resolution imaging with striking anatomical detail
  • MRI is choice method for detecting low-contrast or small lesions such as MS plaques, low-grade astrocytomas, etc. (CT not as sensitive in detection of white matter or neurodegenerative disorders)
  • The only cranial nerve observable by CT is the optic nerve
  • Provides clear images of basilar structures such as brainstem, cerebellum and pituitary fossa
  • MRI’s cost more and take longer; also inferior performance in imaging fresh hemorrhage and bony structures
  • CT preferred with head trauma or suspected intracranial hemorrhage as a 1st screening – easier to perform on ventilated patients and do not get artifacts from implanted devices
  • In non-urgent situations in which a single more definitive image method is desired, MRI is test of choice

Magnetic Resonance Imaging (MRI)

(Review normal MRI scans in Figures 4.13-4.15)

  • Developed from NMR
  • Powerful magnetic field causes protons to align intrinsic spins
  • Protons relevant to conventional MRI are only those forming hydrogen nuclei
  • Unlike CT scans, MRI scans are not described in terms of density. Instead are described in terms of intensity, or brightness of the signal
    • Hyperintense – brighter areas
    • Hypointense – darker areas

T1 versus T2 Weighted Images

  • T1 weighted images – look like anatomical brain sections
  • T2 weighted images – look like film negatives
    • As such, T1 gray matter is gray, and white matter is white; T2 images are the opposite
  • T1 better for identifying anatomy because resolution is better
  • T2 better for detecting pathological changes; poorer resolution, but better contrast

MRI and CT Appearance of Commonly Scanned Tissues

Tissue T1 Weighted T2 Weighted CT Scan
Gray Matter Gray Light Gray Gray
White Matter White (bright) Dark Gray
CSF / Water Black White Dark Gray
Fat White Black Nearly Black
Air Black Black Black
Bone / Calcification Black Black White
Edema Gray White
Demyelination / Gliosis Gray White

Proton Density Weighted Images (first echo images)

  • Contrast between gray and white matter is reduced
  • But better at detecting subtle abnormalities in the parenchyma such as small areas of edema or infarction adjacent to CSF —- can be easily seen as bright regions

Factors That Affect Intensity of MRI Images/Signals

  • Protons must be present in order for a signal to be generated, thus, on both T1 and T2 weighted images, air appears black and bony/calcified structures appear dark because of the relatively absence of water protons
  • Images are distorted in patients with metallic implants in the head (e.g., pacemakers, cochlear implants, and old aneurysm clips)

Intracranial Hemorrhage Appearance on MRI

(see table 4.4 on page 92)

  • Undergoes characteristic series of changes over time
  • On both T1 and T2, acute hemorrhage may be hard to see because it’s gray and resembles CSF
  • Subacute contains hemosiderin and appears white
  • Chronic contains dark areas resulting from hemosiderin deposits
    • usually bright center with dark rim
    • eventually, the center may reabsorb, forming a fluid filled cavity that is dark on T1 and bright on T2
  • Infarcts become apparent on T2 within 12-24 hours of onset

Neuroangiography

(Figures 4.16 and 4.17 show samples of angiogram imagery)

  • Definition – the study of central nervous blood vessels and related cervicocerebral vasculature using radiographs during injection of intravascular contrast medium. It is the gold standard for evaluating vascular diseases in head, neck, and spine.
  • Before availability of CT and MRI – was used to detect slight distortions in the patterns of blood vessels suggestive of intracranial mass lesions
  • Now is used to visualize lesions of blood vessels themselves rather than to provide indirect information about surrounding structures
  • Lesions optimally seen by angiography include:
    • Atherosclerotic plaques and other vessel narrowings
    • Aneurysms
    • AVM’s
  • Can also be used during planning of neurosurgery and to assess the vascular anatomy of tumors

Angiography is Invasive

  • Relies upon continuous x-ray guidance
  • Requires local anesthesia
  • Catheter inserted, usually in femoral artery which is threaded up the aorta
  • Radio-opaque iodinated contrast material is injected into carotid and vertebral arteries on both sides, and sequential images are obtained at different times during the injection and runoff

Less Invasive Means for Visualization

(None of these have achieved the specificity or sensitivity of angiography, so risks and benefits must be weighed in each case)

  • Doppler Ultrasound – used to measure flow and lumen diameter of large blood vessels in head and neck (best for assessing atherosclerotic narrowings which occur proximally, not very good at detecting aneurysms or other vascular abnormalities)
  • Magnetic Resonance Angiography (MRA) – detects direction and speed of blood flow; although the major vessels can be seen, the smaller, more distal branches cannot
    • Used primarily to detect regions of decreased or absent arterial blood flow caused by atherosclerotic narrowing, thrombosis or dissection
    • Also useful for detecting some aneurysms and other vascular abnormalities
    • Venous flow can be visualized using Magnetic Resonance Venography (MRV)
  • Spiral CT Angiograpy (CTA) – rapid injection of IV contrast used with helical CT to obtain images of blood vessels quickly – can be used in patients where MRA may be contraindicated (e.g., pacemaker)

Therapeutic Neuroradiography

  • Wada Test – amobarbital is selectively infused into each carotid artery while patient is awake – helpful for localizing language and to aid plans for neurosurgery
  • Treatment of brain aneurysms and AVM’s – these can sometimes be clotted off and rendered harmless by filling them with glue-like material or tiny metal springs via the angiography catheter
  • Stroke – therapeutic trials are underway in which thrombolytic agents are infused directly at site of clot to try and reestablish perfusion (performed within 6 hours of acute symptoms)
    • With CT or MRI can be used to diagnose venous occlusive disease following stroke

Ultrasonography

  • Uses sound waves above audible levels to generate diagnostic medical images
  • Indicated when target area is not blocked by bone or air – very useful in pediatrics especially because of lack of ionizing radiation
    • Direct brain imaging in peds is possible b/c of presence of fontanelles which remain open until 6-9 months of age
    • In young children can be used to detect brain structures and congenital abnormalities; also used to grade hemorrhages
  • Not good at detecting extra-axial hemorrhages or masses or white matter disease
  • In adults can be use to detect vascular lesions of head and neck

Functional Neuroimaging

EEG

  • Original method for measuring brain activity
  • Sensitivity and spatial resolution in detecting focal brain lesions is poor
  • Useful in evaluating for epileptic (seizure producing) brain activity
  • Useful in detecting widespread abnormality in brain function

Evoked Potential

  • Similar to EEG in which brain electrical activity is recorded in response to specific stimuli
  • Quantitative EEG Analysis and Magnetoencephalography (MEG), which uses a superconducting quantum interference device (SQUID) to detect very weak magnetic signals- for research only

Imaging Using Blood Flow or Dynamic Blood Flow Volume

  • Xenon regional cerebral blood flow mapping (Xe rCBF)
  • Positron emission tomography (PET)
  • Single photon emission computerized tomography (SPECT)
  • Dynamic contrast functional MRI (perfusion MRI)
  • Blood oxygen level dependent functional MRI (BOLD fMRI)

PET Studies

  • Can be useful with brain tumors
    • High grade neoplasms demonstrate increased metabolism
    • Low grade neoplasms demonstrate decreased activity
  • Radiation necrosis shows decreased activity and tumor recurrence shows increased metabolic activity
  • SPECT is more limited in evaluating tumors

Functional MRI (fMRI)

(refers to several different MRI techniques)

  • Perfusion MRI – rapid injection of gadolinium and rapid measurements with “echo planar” imaging to produce an image of dynamic blood volume
  • BOLD fMRI – Measures relative changes in oxy and deoxyhemoglobin, which occur with changes in regional cerebral blood flow. Can be used to localize regions of sensory-motor function and language function (may eventually replace the WADA test)
  • Diffusion MRI – Rapid echo planar imaging and strong gradients to measure the diffusion coefficient of water in brain tissue; can detect early areas of ischemia long before conventional MRI
  • Magnetic Resonance Spectroscopy (MRS) – Detects local concentrations of certain chemicals in the brain including some neurotransmitters

Ictal-Interictal SPECT Difference Imaging

  • Can be used to indirectly measure regional brain activity during seizures and to help localize their region of onset
  • Demonstrated decreased regional cerebral blood flow between seizures and increased regional cerebral blood flow ictally

Using Brain Imaging Techniques to Assess Neurological Disorders

  • Two general types:
    • Structural Techniques Includes computerized tomography (CT) and magnetic resonance imaging (MRI). CT uses x-rays to look at slices of the brain, providing information on the density of brain tissue and is useful for identifying tumors, blood clots, tissue damage,a nd other structural abnormalities. MRI uses magnetic fields to produce three-dimensional images of the brain. Advantages of an MRI over a CT scan are that it produces a more precise image and doesn’t require x-rays.
    • Functional Techniques Provide information about both the structure and the function of the brain. Positron emission tomography (PET) uses small amounts of injected radioactive material. It assesses neural activity by measuring regional cerebral blood flow, glucose metabolism, or oxygen consumption. PET scans are useful for mapping the distribution of neurotransmitters and identifying brain dysfunction due to stroke, epilepsy, tumor, dementia, and other brain-impairing conditions. Other techniques include single photon emission computed tomography (SPECT) and functional MRI (fMRI).

Neuroanatomy

Basic Macroscopic Organization of the Nervous System

  • The CNS arises from a sheet of ectodermal cells that folds over during embryological development to form the neural tube
    • CNS = Brain and spinal cord
    • PNS = Cranial nerves and ganglia
    • Spinal nerves and dorsal root ganglia
    • Sympathetic and parasympathetic nerves and ganglia
    • Enteric nervous system

Main divisions and subdivisions of the human CNS (saggital view of divisions p.15)

  • Prosencephalon (forebrain)
    • Telencephalon
      • Cerebral hemispheres
      • Cerebral cortex
      • Subcortical white matter
      • Basal ganglia
      • Basal forebrain nuclei
    • Diencephalon
      • Thalamus
      • Hypothalamus
      • Epithalamus
  • Mesencephalon (midbrain)
    • Cerebral peduncles
    • Midbrain tectum
    • Midbrain tegmentum
  • Rhombencephalon (hindbrain)
  • Metencephalon
    • Pons
    • Cerebellum
  • Myelencephalon
    • Medulla
  • Spinal cord
  • cerebrospinal fluid (CSF) is formed mainly by vascular tufts lying within the ventricles and choroid plexus
  • CSF circulates from the lateral ventricles to the third ventricle, and then leaves the ventricular system via

foramina in the fourth ventricle, to percolate around the outside surface of the brain and spinal cord; once it leaves the ventricular system it travels in the space between the arachnoid and pia layers and is ultimately reabsorbed into the venous system

  • The CNS is covered by three membranous protective layers called meninges
  • Meninges (from inside to outside): pia, arachnoid, and dura (“PAD”)

Orientation and Planes of Section

  • Ventral (“belly”) – always toward the earth
  • Dorsal (“back”) – toward the sky
  • Rostral (“beak”) – toward the snout
  • Caudal (“tail”) – toward the tail

Note: in humans, below the midbrain these terms apply as if the person is on all fours like dog, but above the midbrain the terms

apply to the brain as if they are standing upright – see diagram p. 16

  • Anterior – forward, front
  • Posterior – rear
  • Superior – above
  • Inferior – below
  • Planes of section, as in CT and MRI scans (diagram p. 17):
    • Horizontal/Axial/Transverse – perpendicular to long axis of the body
    • Coronal – approximating a plane as that of a tiara-like crown
    • Sagittal – in the direction of an arrow shot, like the profile of an archer, as in the constellation “Sagittarius”
      • midsagittal: passing through the midline
      • parasagittal: just off the midline

Basic Cellular and Neurochemical Organization of the Nervous System

  • Neuron support cells: glial cells or glia
  • A typical neuron consists of:
    • cell body – containing the nucleus
    • dendrites – short processes that receive most inputs to the cell
    • axons – long processes carry most outputs
  • Review diagram of “Typical Mammalian Neuron” – p. 18
  • multipolar – has several dendrites and several axons (most mammalian neurons are multipolar)
  • axon collaterals – axons that branch off the main axon to reach different targets
  • bipolar – single dendrite and single axon arises from the cell body; bipolar neurons are often sensory neurons, such as those involved in vision or olfaction
  • unipolar – occur mainly in invertebrates, both axons and dendrites arise from a single process coming off the cell body
  • synapse – gap or space between two neuron structures in which communication occurs
    • Typically, from an axon terminal of one neuron to the dendrites of another neuron
    • However, there are also axo-axonic, dendro-dendritic, and in some cases communication can even occur in reverse, from dendrites to axon
    • chemical neurotransmitter molecules, stored mainly in synaptic vesicles, are released from presynaptic terminals. They then bind to neurotransmitter receptors on the postsynaptic neuron, giving rise to either excitation or inhibition of the postsynaptic neuron
    • in some cases, communication also takes place at electrical synapses where direct electrical coupling of neurons occurs through specialized junctions
  • action potential – a transient voltage change that occurs when excitatory synaptic inputs combine with endogenous transmembrane currents to sufficiently excite a neuron, lasts about 1 millisecond and can travel rapidly throughout the length of a neuron at rates of up to around 60 meters per second. Classically, they travel from the dendritic end of a neuron along its axon to reach presynaptic terminals
  • myelin sheath – insulating lipid layer of an axon formed by specialized glial cells; speeds the rate of action potential conduction
  • myelin-forming glial cells in the CNS are oligodendrocytes, in the PNS they are called Schwann cells
  • nodes of Ranvier – short exposed segments of axon where voltage-gated ion channels are concentrated; conduction from node to node occurs rapidly by a process called saltatory conduction
  • Two general types of functions of chemical neurotransmitters:
    • mediate rapid communication between neurons through fast excitatory or inhibitory electrical events called excitatory postsynaptic potentials (EPSPs)
    • inhibitory postsynaptic potentials (IPSPs); fast EPSPs and IPSPs occur in tens of milliseconds, and rapidly move the membrane voltage of the postsynaptic neuron between states more or less likely to fire an action potential. The postsynaptic neuron summates EPSPs and IPSPs arising from many presynaptic inputs
  • neuromodulation, generally occurring over slower time scales; it includes a broad range of cellular mechanisms involving signaling cascades that regulate synaptic transmission, neuronal growth, and other functions; it can either facilitate or inhibit subsequent signaling

Important Neurotransmitters summarized in a Table on p. 20

  • Most common excitatory CNS neurotransmitter: glutamate
  • Most common inhibitory CNS neurotransmitter: GABA (gamma-aminobutyric acid)
  • Main transmitter at neuromuscular junctions (PNS): acetylcholine
  • Both acetylcholine and norepinephrine are important in the autonomic nervous system

CNS Gray Matter and White Matter; PNS Ganglia and Nerves

  • white matter: made up of mainly myelinated axons (communication over large distances)
  • gray matter: made up of mainly cell bodies (most local communication between neurons in the CNS occurs in gray matter
  • cerebral cortex: unique mantle of gray matter over surface of cerebral hemispheres
  • nuclei: large clusters of cells (gray matter) located deep within the hemispheres and brainstem (includes the basal ganglia, thalamus, and cranial nerve nuclei
  • Note: in the cerebral hemispheres, the gray matter is on the outside and white matter on the inside, but in the spinal cord the reverse is true (white outside, gray inside); in the brainstem – grey and white are found on inside and outside, but most of outside is white matter
  • White matter pathways have several different names: tract, fascicle, lemniscus, and bundle
  • commissure – white matter pathway connecting identical structures on right and left sides
  • Axons in the PNS form bundles called peripheral nerves
  • Clusters of PNS cell bodies: ganglia
  • afferent – pathway carrying a signal toward a structure (afferents “arrive”, efferents “exit”)
  • efferent – pathway carrying a signal away from a structure

Spinal Cord and Peripheral Nervous System

  • Throughout the nervous system, motor systems tend to be more ventral, or anterior; sensory systems more dorsal, or posterior. The same is true for the spinal cord.
  • dorsal nerve roots convey mainly afferent sensory information into the dorsal spinal cord
  • ventral nerve roots carry mainly efferent motor signals from the ventral spinal cord to the periphery
  • See Figures 2.8, 2.9 (pp. 22-23)
  • cervical, thoracic, lumbar, and sacral nerve roots are displayed in the figures
  • plexus, as in brachial plexus (arm) and lumbosacral plexus (leg), is an elaborate meshwork of peripheral nerves
  • control of the arms and legs require more signal flow than does control of the chest and abdomen, thus the thickness of the spinal cord increases in those areas, producing the cervical enlargement and lumbosacral enlargement
  • autonomic nervous system is divided into sympathetic and parasympathetic
  • sympathetic – arises from thoracic and lumbar spinal levels and releases norepinephrine onto end organs, and is involved in “fight or flight” functions
  • parasympathetic – arises from the cranial nerves and from the sacral spinal levels (S2 – S4), it releases acetylcholine onto end organs and is involved in sedentary functions, such as increasing gastric secretions and peristalsis, slowing heart rate, and decreasing pupil size

Cerebral Cortex: Basic Organization and Primary Sensory and Motor Areas

  • I won’t list the four main lobes of the brain, cuz if ya don’t know ‘em yet, ya may wanna rethink this whole ABPP thing
  • sulci – crevices/infolds of brain; deep sulci: fissure
  • gyri – bumps or ridges between sulci
  • insular cortex (Figure 2.24B – p. 42)
  • operculum – “lip”; frontal operculum and parietal operculum (Figure 2.24B – p.42)
  • longitudinal fissure (or interhemispheric fissure) – midline fissure separating the two hemispheres

Surface Anatomy of the Cerebral Hemispheres in Detail

  • STUDY Figure 2.11 (pp. 26-27)…….Learn It, Love It, Live It
  • corpus callosum – main bridge/pathway between the two cerebral hemispheres
  • divisions of the corpus callosum, anterior to posterior: rostrum, genu, body, splenium
  • cingulum (cingulate gyrus) means “girdle” or “belt”
  • lingula (“little tongue”) – portion of the medial occipital lobe below the calcarine fissure
  • cuneus (“wedge”) – portion above the calcarine fissure
  • gyrus rectus (“straight gyrus”)

Primary Sensory and Motor Areas

  • Study Figures 2.12 and 2.13 (pp. 28-29)
  • Note the location of the primary auditory cortex on Heschl’s gyrus
  • Note that sensory and motor pathways are topographically and somatotopically organized in the form of a homunculus (“little man”)
  • Similarly, retinal areas are mapped onto the cortex in a retinotopic fashion
  • Also, adjacent areas of the cochlea sensing different frequencies have a tonotopic representation
  • Of course, primary motor and somatosensory cortex are lateralized to the opposite side of the body
  • Primary visual cortex represent visual inputs from the opposite visual field
  • However, auditory cortex is less lateralized, and represents more of a mixture of inputs from both ears (input from the opposite ear is slightly stronger, but not usually clinically detectable)

Cell Layers and Regional Classification of the Cerebral Cortex

  • The neocortex has six cell layers (listed from the surface inward)
  • Layer I (molecular layer)
    • dendrites and axons from other layers
  • Layer II (small pyramidal layer)
    • cortical-cortical connections
  • Layer III (medium pyramidal layer)
    • cortical-cortical connections
  • Layer IV (granular layer)
    • receives inputs from thalamus
  • Layer V (large pyramidal layer)
    • sends outputs to subcortical structures (other than thalamus)
  • Layer VI (polymorphic layer)
    • sends outputs to thalamus
  • The relative thickness of the cell layers varies according to the function of that area of the cortex. For example, primary motor cortex has a thicker layer V, because there are many more cell bodies than, say, layer IV. However, layer IV is thicker in a sensory area, such as primary visual cortex
  • You should know that Korbinian Brodmann published a map of the cortex in 1909, based on cytoarchitectonic areas (areas based on the microscopic appearance of different regions of the cerebral cortex). Often referred to as “Brodmann’s Areas”. Table 2.4 (p.31) lists them all.
  • You should know at least the following Brodmann’s areas: 1-3, 4-8, 9-12, 17-19, 22, 39, 41, 44,

Motor Systems

Main Motor Pathways

  • Most important motor pathway: corticospinal tract (pathway involving primary motor cortex to spinal cord)
  • pyramidal decussation – where the majority of the motor fibers (~85%) crossover to control movement of the opposite side of the body; this occurs at the medulla/spinal cord junction
  • lesions above the decussation result in contralateral (opposite side) weakness: lesions below the decussation result in ipsilateral (same side) weakness
  • upper motor neurons – motor neurons projecting from cortex to spinal cord or brainstem
  • lower motor neurons – their axons project out of the CNS via anterior spinal roots (or cranial nerves) to reach muscle cells in the periphery (see Fig. 2.16, p.33)

Cerebellum and Basal Ganglia

  • the cerebellum and basal ganglia act by modulating the output of the corticospinal and other descending motor systems; they also receive inputs from the brainstem and spinal cord
  • they project back to the motor cortex via the thalamus
  • lesions of the cerebellum: ataxia (disorder of coordination and balance)
  • lesions in the basal ganglia cause:
  • hypokinetic movement disorders such as Parkinsonism
  • hyperkinetic movement disorders such as Huntington’s disease

Somatosensory Systems

Main Somatosensory Pathways

  • There are 2 main pathways in the spinal cord for somatic sensations:
  • posterior column pathway (dorsal column/medial lemniscus) – proprioception, vibratory sense, and fine touch (Fig 2.18 – p.35)
  • anterolateral pathway (anterolateral system) – pain, temperature, and crude touch (Fig 2.19 – p. 36)

since some aspects of touch are carried by both pathways, touch sensation will not be eliminated by isolated lesions in either pathway

  • Thalamus – important relay center consisting of multiple nuclei – (discussed in Chp.7)

Brainstem and Cranial Nerves

  • STUDY Fig. 2.22 (pp. 38-39)……….learn the locations of the main structures of the brainstem
  • MEMORIZE the 12 Cranial Nerves by number and name so they are interchangeable in your mind and develop an understanding of their function (Table 2.5 p.40)
  • reticular formation – extends throughout the central portions of the brainstem from the medulla to the midbrain; the rostral portion plays an important function in regulating the level of consciousness

Limbic System

  • limbus = “fringe” (medial edge of the cerebral cortex)
  • olfaction and regulation of emotions, memory, appetite drives, and autonomic and neuroendocrine control
  • includes medial and anterior temporal lobes, anterior insula, inferior medial frontal lobes, and cingulate gyri; also includes the hippocampal formation, amygdala, medial thalamic nuclei, hypothalamus, basal ganglia, septal area, and brainstem
  • these areas are interconnected by a variety of pathways, including the fornix, a paired, arch-shaped white matter structure connecting the hippocampal formation to the hypothalamus and septal nuclei
  • lesions can cause: deficits in encoding, behavioral changes and psychiatric disturbance, and epileptic seizures

Association Cortex

  • unimodal – association cortex where higher-order processing takes place mostly for a single sensory or motor modality; it’s usually located adjacent to a primary motor or sensory area
  • heteromodal – association cortex involved in integrating functions from multiple sensory and/or motor modalities
  • Examples of heteromodal cortex:
    • Wernicke’s area – in the dominant (usually left) hemisphere; lesions cause deficits in language comprehension
    • Broca’s area – located in the frontal lobe (usually left); lesions cause deficits in production of language, with relative sparing of language comprehension
    • Inferior parietal lobule – lesion can produce Gerstmann’s syndrome: acalculia, right/left confusion,

finger agnosia, and agraphia

Other lesions of association cortex can cause:

  • apraxia – poor sequencing of motor movements
  • hemineglect – neglect of one side of space (and sometimes body), usually left
  • anosognosia – impaired self-awareness, especially of deficits
  • frontal release signs – primitive reflexes that are normal in infants, such as grasp, root, suck, and snout reflexes
  • perseveration
  • disinhibition
  • abulia – tendency to stare passively, respond after long delay, poor initiation
  • magnetic gait – feet shuffle close to the floor
  • urinary incontinence
  • prosopagnosia – inability to recognize faces
  • achromatopsia – inability to recognize colors
  • palinopsia – persistence or reappearance of an object viewed earlier

Neglect

DEFINITION

  • Neglect: a failure to respond to, report, or orient to novel or meaningful stimuli presented to the side opposite the lesion
  • NOT attributable to sensory, motor, or memory deficits deficit of looking, detecting, listening, and exploring NOT seeing, hearing, or moving
  • Like aphasia or amnesia, neglect is a “network syndrome” and represents damage to one or more components of a distributed network
  • Also has been described as unilateral spatial agnosia, amorphosynthesis, left-sided fixed hemianopia, hemi-inattention, hemineglect, hemispatial agnosia, etc.

HISTORY

  • Jackson (1867) first to present well-documented account
  • Extensively described by Brain (1941)
  • 1970s saw resurgence in interest

GENERAL CLINICAL ISSUES

  • Characterized by reduction of neural resources mobilized by sensory events and motor plans on left
  • Most dramatic aspects occur in visual sphere, but also seen in auditory, somatosensory, olfactory
  • Neglect behaviors can be classified into 3 components:
  • Sensory-Representational
    • Sensory neglect or inattention is a form of selective unawareness
    • May be defined by its modality (eg, tactile, visual, auditory) and distribution (eg, hemispatial, personal)
    • Pts behave as if sensory events on L lost impact on awareness, especially when competing events on R
    • Probed w/ tests of extinction, line bisection, and covert attentional shifts
    • Another useful probe is to have pt close eyes and point toward body midline; usually pt rt of midline
  • Motor-Exploratory
    • Reluctance to scan and explore L hemispace
    • Probed w/ tasks of target detection (the more difficult, the more sensitive in detecting; eg, letters better than lines; complex shapes better than letters, etc.)
    • L-sided target detection failures reflect both: decreased tendency to explore L and attraction to R side
    • Neglect dyslexia involves failure to read words on left side of page
    • “Intentional Neglect” or “limb akinesia” reluctance to move limbs on L (in absence of damage to corticospinal system)
    • “Hemispatial akinesia” is better movement in ipsilesional than contralateral space
    • “Hypokinesia” is milder form of intentional neglect, in which delay in initiating movement
  • Limbic-Motivational
    • Major role of attentional system is to shift attentional searchlight toward emotionally or motivationally salient events
    • Neglect pts devalue the L side of space and act as if nothing of importance could happen on that side

CLINICAL MANIFESTATIONS OF NEGLECT

  • Inattention
    • failure to report or respond to stimuli presented contralaterally, but may be able to detect the stimulus if pt’s attn is directed to that side (so different than hemianopia or other primary sensory pxs)
    • may even fail to recognize that their contralateral extremities are their own
    • in milder cases they will recognize that the limbs are theirs (b/c they’re attached), but they refer to them as though they were objects
  • Allesthesia (sometimes referred to as allochiria)
    • disturbance of body schema perception in tactile modality in which stimulation on one side of body is perceived as located on other side
    • similar phenomena may occur in other modalities
  • Sensory Extinction to Double Simultaneous Stimulation
    • patients w/hemi-inattention usually improve so that they are able to detect and lateralize stimuli, but often when they are stimulated bilaterally they fail to report the contralateral side
    • may affect one or more sensory modalities
  • Action Intentional Disorders (Motor Neglect); 4 types:
    • Akinesia: pt fails to spontaneously use contralateral body part, although when focusing on that extremity they may show good strength; may involve different body parts (eyes, arms, head)
    • Hypokinesia: may initiate response, but after a long delay; may be obvious or need RT testing
    • Motor Extinction: patients who do not demonstrate akinesia when they move one limb may demonstrate contralateral akinesia when they must move both limbs simultaneously
      • may report moving both limbs, but will only move one
    • Motor Impersistence: inability to sustain motor act; have them move for 10-20 seconds
  • Spatial Neglect
    • Spatial neglect may occur in all three dimensions of space: horizontal, vertical, and radial (near, far)
    • patient neglects the hemispace contralateral to the injured hemisphere
    • seen on tests of line bisection, target cancellation, and drawing
    • frequently fail to dress or groom abnormal side
    • hemispatial neglect pts can use both a body-centered frame of reference and environmental frame of reference
  • Neglect can also be classified by one of the following sectors of space
    • Personal neglect: attn disturbances to contralateral side of body (eg, fail to groom or even dress one side of body)
    • Peripersonal neglect: attn disturbances w/in reaching or grasping space
    • Far extrapersonal neglect: attn disturbances may be detected only when stimuli are out of reach

ASSOCIATED CLINICAL BEHAVIORS/SYNDROMES

  • Anosognosia (also associated w/other disorders)
    • unawareness or denial of deficits – even sometimes that the paretic limb belongs to them
    • most associated with damage to rt. hemisphere (when the left hemisphere is damaged, more likely to have a catastrophic reaction)
    • behavioral examples: if you ask them to do a task with their impaired limb, they may say, “oh, I’m left handed” (w/rt hemiplegia), or they may say they have done the task when they haven’t
    • can be specific to particular disorders; e.g., Bisiach studied patients w/both hemiplegia and hemianopia; patients were unaware of either or both disorders (depending on the patient)
  • Anosodiaphoria
    • Pt will admit to sensory/motor impairment but be entirely unconcerned about it (in psychogenic pts, similar phenomenon called La Belle Indifference)
    • May follow a period of anosognosia
  • Allokinesia
    • pt moves ipsilateral extremity when tasks requires movement of contralateral extremity
  • Visuospatial deficits

FUNCTIONAL NEUROANATOMY OF NEGLECT

  • Neglect much more frequent, severe after lesions of R hemisphere since R hemi specializes in spatial distribution of attention
    • Left hemi attributes salience and directs attn to RIGHT side
    • Right hemi attributes salience and directs attn to BOTH sides (w/ slight contralateral bias)
    • Right hemi devotes more neural resources to spatial attn
  • Attentional network includes three cortical regions; any component can cause neglect (Mesulam)
  • Parietal component (inferior parietal lobe)
    • Seems to play its key role in spatial attn NOT as multimodal spatial map but as critical gateway for linking distributed channels of motor output
    • When parietal component destroyed, individual input/output channels may remain intact but can’t be integrated
    • Small lesions rarely lead to neglect, usually large and involve subcortical components
  • Frontal component
    • May play its critical role in network by converting plan and intentions into specific sequences of motor acts that shift the focus of attn; Frontal Eye Fields select/sequence individual acts needed to explore
    • Lesions confined to right frontal lobe can cause neglect just as severe as parietal lesions
    • Important regions unclear, but likely Frontal Eye Fields or inferior frontal gyrus
  • Limbic component
    • Cingulate component least understood, but may play critical role in identifying motivational relevance of extrapersonal events and sustaining level of effort during attentional tasks
    • Can have neglect w/ lesions to cingulate gyrus, though rare
    • Cingulate component may have two parts:
      • anterior part reflecting global attentional engagement
      • post part which may participate in more differentiated lateralized shifts of relevance and focal attn
  • Subcortical components of attentional network:
    • Includes thalamus, striatum, and superior colliculus
    • Thalamic neglect: deficit attributed to problem w/ engaging, not the disengaging problem seen w/ parietal lesions

ETIOLOGY

  • Usually consequence of focal lesions involving right
    • Most common cause is CVA; also can see w/ fast-growing tumor, seizures
  • More generalized injury rarely leads to neglect so don’t typically see from toxic-metabolic encephalopathy, subdural hematoma, neurodegenerative diseases, head injury

MECHANISMS UNDERLYING NEGLECT

Precise mechanisms still unclear, but over the years, literature divided into two camps (w/ attentional hypothesis now more accepted):

Representational Hypotheses

  • Bisiach (1978, 1981) (representative of approach)
    • Posterior parietal cortex contains an elaborate spatial representation of the external world
    • Unilateral injury causes unilateral loss of spatial representation and thus neglect
    • Classic experiment: pts describe the Piazza del Duomo (cathedral) in Milan; pts failed to describe landmarks imagined on left side of scene
    • Interpretation of data unclear
    • Could mean: a) impaired representation b) impaired scanning of intact representation c) or inability to attend to contralesional hemispace
    • Seems clear that improved performance upon cueing pts to left implies attentional component, which not readily explained by representational view

Attentional Hypotheses (sample views below)

  • Heilman’s (1977) Unilateral Akinesia Hypothesis ~ theory – associated with hypoarousal
    • A defect in orienting to stimuli due to a disruption of the system whose function it is to “arouse” the individual when new sensory information is present
    • Neglect results from decreased activation of arousal systems of damaged hemisphere
    • Effect of unilateral decrease in arousal is selective loss of orienting rx to contralateral hemisphere
    • Damaged hypoaroused hemisphere rendered akinetic
    • View revolutionized conceptualization of neglect, but number of problems (e.g., why don’t most severe cases of neglect follow damage to reticular activating system)
  • Posner’s (1982, 1984) Covert Orienting Hypothesis ~ disengage, shift, engage model of attention
    • Neglect results from impairment in mechanisms allowing attn to be shifted away from intact hemispace, rather than an inability to direct attn to impaired side
    • Neglect pts find it remarkably difficulty to disengage attn from ipsilesional hemispace
    • First to accommodate findings that cueing reduced severity of neglect errors, but selective deficit in visual attn can’t explain all findings since neglect not specific to visual modality
  • Mesulam’s Attentional Network Hypothesis (lots of above based on Mesulam’s model)
    • Neglect is a “network syndrome” and represents damage to one or more components of a distributed network (Involves the above outlined parietal, frontal, and limbic components)
    • Represents a domain-specific impairment of spatial attention

ASSESSMENT ISSUES

  • Differential Diagnosis
    • Need to rule out primary sensory deficits, which are not ameliorated by attentional cues
    • Unilateral hearing loss does NOT occur following unilateral lesions (if does, then it’s neglect)
    • Visual field cuts are NOT affected by the position of the eyes in space (neglect is)
    • Pts w/ neglect show normal sensory evoked potentials
  • Assessment should include at least three modalities
    • auditory
    • visual
    • somesthetic
  • Informal Testing (bedside: gaze, dressing, motor, etc.)
  • Standardized Testing
    • Cancellation tasks: look at omissions and search strategy
    • Line bisection: large deviations to ipsilateral side
    • Drawing: copy or draw clock (which is less sensitive to visuoconstructional deficits)
    • Reading and writing

TREATMENT

  • First and foremost, should treat underlying cerebral disease
  • Management of environment
    • need to arrange the environment to reduce risk of injury
    • since neglect is often in reference to patient’s midsagittal plane, pt should be positioned such that environmental stimuli are on right
    • reduce competing or distracting stimuli
    • when detecting stimuli not critical, pts should receive stimuli in neglected fields since may be therapeutic
  • Training
    • some evidence that pts w/ neglect can be trained to explore contralesional space w/ operant techniques
    • But, may remain task specific and not generalize
  • Cueing
    • Attentional cues may help pt attend to contralesional hemispace
    • Bottom up cues include providing novel stimuli
    • Top down cues include providing directions to attend to neglected side
    • Ultimate goal would be to have them know to search to left, before engaging environment
    • Motor neglect may improve if have pt uses left arm (even small movements of left may help)

Multiple Sclerosis

General Characteristics

Multiple sclerosis is a multifocal demyelinating disease – the disease causes the destruction of the myelin sheath of nerve fibers – scar-like lesions called sclerotic plaques form in the areas where the demyelination has occurred and block or distort the normal transmission of nerve impulses.

  • Incidence and prevalence vary geographically
    • fewer cases near the equator and larger numbers in the northern and southern latitudes
      • between 250,000 to 350,000 people with MS in the United States, with three times more cases among residents in the northern (versus southern) half of the country.
        • this distribution suggests an environmental contribution to the disease
    • MS is twice as likely to affect women than men
  • Two severity outcomes defined
    • Benign outcome: Full functioning for 15 years post onset
    • Malignant outcome: rapidly progressive course with significant disability or death soon after onset

Diagnosis

  • Can be difficult to diagnose in early stages b/c of its presentation
  • Diagnosis requires the occurrence of 2 or more attacks each lasting a minimum of 24 hours and separated by at least a month.
  • The attacks must also be caused by lesions in 2 distinct areas of the CNS
  • Diagnosis rests on clinical grounds
  • MRI’s can be used to detect demyelinating plaques in the brain
    • BUT other disease can cause similar imaging patterns – e.g., AIDS and Lyme disease
    • Plaques have predilection for periventricular white matter of brain (L/R hemisphere equally affected)
    • Extent of plaques and total lesion area is related to cognitive fxing, but in general location of plaques is not predictive
  • CSF analyses – can be used to detect oligoclonal abnormalities

Etiology

  • Actual etiology is unknown, but data implicates:
    • Genetic variables – 1st degree relatives of affected individuals are 6-8 times more at risk than the general population, with siblings being most at risk; women:men = 2:1
    • Environmental variables – siblings who develop MS do so in the same calendar year rather than at the same age
      • prevalence rates of MS decreases systematically as latitude of habitation nears the equator
      • those who move from high-risk latitude to a low-risk latitude (e.g. Europeans moving to South Africa) or vice-versa carry with them some of the risk from their place of origin if their movement occurs after the age of 15 — disease acquisition is believed to occur before puberty
    • immunologic variables
    • Proposed explanations include a slow acting virus, a delayed reaction to a common virus, or an autoimmune reaction in which the body attacks its own tissues

Treatment

  • Corticosteriods, adrenocorticotropic hormone (ACTH) and other anti-inflammatory agents may be used during exacerbation to hasten remission
    • These drugs are known to produce mood changes and should be considered when assessing affective changes in patients with MS
  • Now introducing immunomodulators (e.g., interferon B-1-a) to treat, but even these still can’t arrest or cure

Disease Course

  • Deficits partially resolve as inflammation subsides; also can be suppressed with steroids, but with more attacks more plaques develop and permanent deficits occur
  • Approximately 50% have a mixed or generalized type, which involves the optic nerve, the brain, the cerebellum, and the spinal cord
  • 2/3 of people are diagnosed between the ages of 20-40 (average 30); although the transient and variable nature of MS symptoms make it difficult to diagnose (mean delay of 3.5 – 4 years from time of onset to diagnosis has been documented)
    • likely acquired before puberty however
      • onset before 15 rare
    • onset after 40 typically characterized by quicker progression and shorter length of survival
  • Typical lifespan following MS onset about 30 years, but this varies

Disease Categories

(Categories imprecise at best)

  1. Relapsing/Remitting (most common in early years – about 90%)
  2. Primary progressive
  3. Secondary progressive – initially relapsing-remitting course followed by progression with or without occasional relapses, minor remissions and plateaus
  4. Progressive relapsing (rarest) – progressive disease from onset with clear acute relapses, periods between relapses characterized by continuing progression

General Symptoms

  • Early symptoms commonly include:
    • Weakness in one or more limbs
    • Bladder dysfunction – includes urinary urgency, frequency, dysuria, nocturia, and incontinence
    • Optic neuritis (i.e., inflammation, demyelination or degeneration of the optic nerve)
      • results in temporary or total loss of vision, usually occurring over several hours or days
      • retrobulbar neuritis – optic neuritis that occurs far enough behind the optic disk that no early changes of the optic disk are visible by opthalmascope (MS is the most common cause for this)
    • Acute Myelitis (Transverse Myelitis) – common designation for an acutely evolving inflammatory-demyelinative lesion of the spinal cord, which often is expression of MS
    • Other neurological signs
      • e.g., vertigo, seizures, nystagmus, ataxia, diplopia, hemiplegia, deafness, neuropathy, aphasia and emotional changes
      • Charcot’s Triad: nystagmus, dysarthria, and tremor
      • Spinal Cord (3 I’s): incontinence, impotence, impairment of gait
  • Other common symptoms
    • spasticity
    • fatigue – one of the most common and debilitating complaints, affecting upto 90% of patients
    • psychiatric changes – including affective disturbances, psychoses and personality changes
      • believed to be due to the disease process rather than (only) a psychological response to the illness

Cognitive Symptoms

Cognitive symptoms have been reported in the early stages of the disease, but they become more evident as more white matter is affected

  • Overall prevalence of cognitive symptoms between 40-70%
    • Of the people with cognitive impairment, 80% of these folks have mild impairments
    • Even mild cognitive problems in MS are enough to interfere with day-to-day activities
  • Pattern of impairments more likely to resemble patients with frontal and subcortical lesions
  • Receptive and expressive language skills are generally spared (although mild deficits in naming and word generation are common)
  • Cognitive symptoms result from demyelination rather than gray matter lesions
  • Most common deficits are in memory, complex attention/speed of information processing and executive functions
  • basic cognitive profile (consistent with subcortical dementia, although because procedural memory spared might be considered White Matter Dementia):
    • little or no language deficit
    • impairment in retrieval from long-term memory, but normal recognition, immediate recall, and rates of forgetting
    • impaired abstract and conceptual reasoning, slowed rates of information processing
    • impaired attention
  • Intellectual Functioning
    • VIQ>PIQ (likely reflects motor impairments)
  • Memory Functioning
    • Some research suggests that memory impairments represent difficulties in retrieval, with storage, encoding, and recognition are generally spared (although this is a somewhat controversial finding)
  • Speed of Information Processing
    • While exaggerated by physical impairment, it also appears to cause an overall slowed speed of processing
    • May contribute to verbal memory impairments
    • commonly manifest as difficulty keeping up with conversations, work tasks
  • Attention
    • may be reflected as reduced span, impaired mental tracking, or slowed complex visuomotor tracking
  • Working memory deficits common
  • Executive Functions
    • Impairments similar to frontal lobe patients (e.g., problems with conceptual flexibility, abstraction, planning and problem solving)
    • Most common w/ chronic-progressive form
    • clinically evident in disinhibition and tangential speech, difficulty planning day-to-day activities, and problems organizing ideas in conversation and speech
  • Motor Slowing
    • Often seen early in course of disease
  • Visual Spatial Functions
    • Generally intact visual spatial skills but 10% to 20% of people with MS show higher order visual spatial processing problems(variable – impairments more related to exec. fxns and motor speed)
    • May be seen clinically as problems running into things while walking (e.g., walls, doors) or driving (e.g., curbs, posts) due to miscalculations
  • Typical areas of preserved functioning (again, may be variable): Memory storage, encoding, recogniton, simple auditory span; motor skill and implicit learing, language skills (aside from fluency), basic visual spatial functions

Affective and Behavioral Functioning

  • Depression is a common finding in people with MS
    • It is sometimes the first or most prominent symptom
    • People with MS have 50% lifetime risk of depression
      • May be exacerbated by high levels of perceived stress, low levels of perceived instrumental and emotional support, disease exacerbation and pharmocological treatment of disease associated with greater distress and depression
      • Notassociated with severity of neurological disability
  • Personality changes – also (rarely) includes euphoria
  • Anxiety also common, and found in about 25% of people with MS, but not well studied
    • May be prominent in early stages of disease when diagnosis and prognosis are unclear
    • comorbidity of anxiety and depression is more associated with somatic complaints and social dysfunction than either anxiety or depression alone
  • Emotional changes may be related to periventricular and frontal white matter lesions
    • Assocations between impairments in complex attention, information processing speed, and perhaps, executive functions and depression have been found
      • may have common neuroanatomical substrate

Differential Diagnosis

  • Dysmyelination
  • Number of conditions that can mimic MS
    • Guillain-Barre Syndrome – demyelinating disease of PNS
      • characterized by monophasic attack, lasting several weeks to months; no cog impairment
    • Leukodystrophies
      • Group of genetically transmitted illnesses
      • Usually manifest in children or adolescents, but sometimes later
      • Cause unremitting physical and mental deterioration
      • Two well-known: adrenoleukodystrophy (ALD) and metachromatic leukodystrophy (MLD)
    • Infections
    • Toxins – numerous toxins preferentially attack CNS myelin
      • Marchiafava-Bignami: possibly caused by substance in homemade red wine and results degeneration of CC
      • Chronic Toluene exposure
    • Lupus: produces CNS changes in only about 5% of cases

Motor Systems

Spinal Cord:

  • Central gray matter – neuronal cell bodies and synapses
  • Peripheral white matter – ascending/descending fiber pathways (motor and sensory)

Muscle Unit:

  • A single motorneuron and all of its muscle fibers
  • Alpha motorneuron – largest cells of spinal cord and “final common pathway” from CNS to periphery. Each one usually innervates many muscle fibers – each muscle fiber innervated by only ONE alpha motorneuron

Spinal Reflex:

  • Stereotyped motor responses to stimuli
  • Afferents from periphery -> synapse(s) in spinal cord -> alpha motorneurons -> muscle fibers

General Info:

  • Motor (corticospinal) pathway extends from motor area of cortex through brain stem and crosses between brainstem and spinal cord
  • Fibers synapse in anterior horn (just prior to leaving cord)
  • Decorticate Posturing – Cerebral injury (e.g., CVA due to carotid occlusion) – flexion of wrist and elbow and extension of ankle and knee
  • Decerebrate Posturing – due to midbrain injury – posturing is similar, but elbow is extended
  • Upper Motor Neurons (i.e. first order neurons) – are neurons above the synapse in the anterior horn
  • Lower Motor Neurons (i.e., second order neurons) – peripheral motor neurons
  • Polio – attacks anterior horn cells – LMN disease
  • Gullian-Barre Syndrome – sensory and LMN loss due to peripheral nerve involvement

Abnormalities of Movement

  • Fasciculation – visible, continuous, and rapid twitching of a muscle or part of muscle without movement of a limb
  • Tremor – rhythmic involuntary back-and-forth movement that may be as rapid as trembling. It usually involves movement of a limb or body part. It may be represent only when the muscle is at rest, during a voluntary movement, or both.
    • In Parkinson’s tremor is present at rest
    • In Cerebellar disorder, tremor is intentional (i.e., occurs during intentional movements, such as drawing)
  • Tics – repetitive twitching of a muscle group such as, facial muscle twitching resulting in grimaces. They may be emotional or neurological origin
  • Chorea – obvious, rapid, sudden, involuntary, jerky movements that may involve the limbs, trunk, or face. They occur at irregular, unpredictable intervals and are not rhythmic or repetitive
  • Athetosis – differs from chorea primarily in that it is slow, writhing, and twisting, rather than rapid and jerky (may occur with cerebral palsey)
  • Myoclonus – sudden, rapid, unpredictable and involuntary jerking movements (e.g., a hiccup is a myoclonic movement of the diaphragm)

Upper Motor Neuron (UMN) Defects

  • Spastic paralysis
  • No significant muscle atrophy
  • No fasciculations/fibrillations
  • Hyperreflexia
  • Babinski may be present

Lower Motor Neuron (LMN) Defects

  • flaccid paralysis
  • significant atrophy
  • fasciculations/fibrillations
  • hyporeflexia
  • No Babinski

Ventromedial Tracts

Axial musculature involved in maintain posture (righting reflex and whole body orientation)

Dorsolateral Tracts

Distal musculature, initiation and control of voluntary movements.

Basal Ganglia

  • Subcortical telencephalic nuclei involved in initiation and control of movement
  • Extrapyramidal – mechanisms involving injury to the basal ganglia motor pathway outside of the corticospinal “pyramidal” system. Consists of:
    • Caudate nucleus
    • Putamen
    • Globus pallidus (pallidum)
    • Associate areas include substantia nigra, subthalamic, nucleus and projections from Basal ganglia to thalamic nuclei
  • Divisions:
    • Neostriatum or Striatum -> caudate -> putamen
    • Corpus Striatum -> striatum -> globus pallidus
    • Lentiform nucleus -> putamen -> globus pallidus
  • Symptoms of Impairment
    • Dyskinesia – involuntary movements
    • Bradykinesias – slowness in initiating or changing without significant weakness
    • Abnormal fixation – equilibrium and righting
    • Parkinson’s Disease – rigidity, bradykinesia, resting tremor, loss of postural reflexes
    • Ballism – sudden, forceful, flinging dyskinesia involving whole limb (contralateral arm to lesion in subthalamic nucleus)
    • Athetosis – slow, wormlike, writhing movements, usually in extremities
      • Lesion in striatum (usually putamen)
    • Torsion Dystonia – disorder of trunk and limb involving writhing movements which produce severe sustained contortion of neck, shoulder girdle, and pelvic girdle
      • Lesion in striatum (usually putamen)
    • Huntington’s Chorea – involuntary movements of limbs which are brisk and graceful and have appearance of fractions of purposeful movement
      • caudate
    • Choreoathetosis – combination of chorea and athetosis

Cerebellum

  • Coordination of movement and posture, particular in adaption of movement to changing external and internal conditions
  • Lesions cause:
    • Ataxia
    • Hypotonia
    • Ipsilateral malfunctioning
    • Dysdiadochokinesia – failure of rapid alternating movements
    • Past pointing – inability to touch finger to nose or heel to shin

Gait Abnormalities

  • Spastic hemiparesis – the arm on the affected side is held flexed and immobile against the body, instead of swinging freely by the side. The affected leg is moved forward stiffly and in a semi-circle, sometimes with the toe dragging on the floor as the leg is moved forward
  • Scissors gait – steps are abnormally short and appear effortful. The knees remain in contact as if the patient were trying to hold an imaginary orange between the thighs as he walks – seen in MS
  • Ataxia – patient has difficulty in keeping his balance. Walks with feed wide apart
  • Parkinsonian – stooped posture, flexion at the hips, elbows, and knees. General mobility is decreased; steps are short and shuffling. Has difficulty both initiating and stopping

Muscle Tone

  • Flaccidity – when muscle tone is less than normal and the limb feels limp to the examiner
  • Posture retention – when a limb tends to remain in the position into which you move it or in which it was before you moved it
  • Rigidity – limb is abnormally resistant to movement in all directions
  • Cogwheel motion – limb yields in your attempt to move it, but with jerking rather than smooth movements (seen in Parkinson’s)
  • Spasticity – impairment of UMN – increase in muscle tension characterized by certain postural changes involving flexion of the finger, hand, arm, and legs