Neurologic Differential

Diagnosis
A Case-Based Approach
 DSM-IV-TR anxiety disorders :

Definition 1. Panic disorder with or without agoraphobia

2. Agoraphobia without history of panic disorder

Cardinal Anxiety : 3. Specific phobia

symptoms emotional state of feeling 4. Social phobia

associated anxious / nervous
5. Obsessive-compulsive disorder
with anxiety
disorders 6. Post-traumatic stress disorder

7. Acute stress disorder

Panic :
8. Generalized anxiety disorder
extreme anxiety associated
with fear, apprehension, and 9. Anxiety disorder due to a general medical condition
terror
10. Substance-induced anxiety disorder

11. Anxiety disorder not otherwise specified

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 Definition

Disorder associated anxiety & panic symptoms Anxiety prominent :

• Chronic (generalized anxiety disorder) • Adjustment disorder with anxiety

• Episodic (panic disorder) • Adjustment disorder with mixed anxiety
depressed mode
Features :
Etiologies :
• Palpitations
• Shortness of breath • Presence of primary psychiatric disorder
• Diaphoresis • Neurologic disorder / other comorbid general
medical conditions
• Hypervigilance
• Coping with the neurologic process / other
• Avoidance comorbid general medical conditions
• Muscle tension • Medications used to treat neuropsychiatric and
• insomnia medical conditions
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 Prevalence

Retrospective
Prospective study
national cohort
Prospective birth noted
comorbidity
cohort study Retrospective studies
replication survey (N
By age 32 may significantly
= 9,282)
(N = 1.000) 49,5% underestimate
Lifetime prevalence
had anxiety disorder lifetime prevalence
28,8% anxiety
rates
disorder

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 Neuroanatomy and
Neurotransmitters

Neuroimaging Neurocircuits
• fMRI
• MRI • Amygdala, hippocampus,
• PET insular cortex, medial prefrontal
cortex, frontal cortex, rostral ant
• SPECT cingulate cortex, dorsal ant
• MRS cingulate cortex, striatum,
Pharmacologic septum, thalamus,
hypothalamus, brainstem
challenge

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 Neurotransmitter &
Neuroanatomy and
Neurotransmitters
neuromodulator imbalances
• Gamma-amino butyric acid
• Serotonin
• Noradrenalin
Medical • Dopamine
• Glutamate
• Histamine
• Directly
Psychiatric
• Indirectly
• Acetylcholine
• Canna binoids
• Neuropeptides
Neurologic • Glucocorticoids
• Cytokines
• Neurosteroid
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 Toxic : abuse and medications
Etiologies Acute, chronic, low-high dose,
overdose

Subdivision Specific entity Possible clinical features

Hallucinogens LSD Anxiety, perceptual distortions, illusions, hallucinations,

Mescaline synethesia, paranoid ideation, ideas of reference, affect
Mushroom lability, depersonalization, panic, depression, suicidal,
Cannabis hyperreflexia, tremor, HT, Hyperthermia, tachycardia,
headaches, myalgia, ataxia, dyspnea, renal failure,
nausea/vomiting, weakness, seizures
Dissociative PCP Altered mental status, anxiety, dysphoria, psychosis,
agents Ketamine violence, delirium, hyperthermia, rhabdomyolysis, seizures,
nystagmus

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 Toxic : abuse and medications
Etiologies Acute, chronic, low-high dose,
overdose

Subdivision Specific entity

Stimulant-hallucinogens Ecstasy (MDMA with active metabolite MDA)

Stimulants Amphetamine
Methamphetamine
Ephedra alkaloids
Methylphenidate

Caffeine

Cocaine

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 Toxic : abuse and medications
Etiologies Acute, chronic, low-high dose,
overdose
Subdivision Specific entity Possible clinical features
Anticholinergics Benztropine Anxiety, agitation, hypertension, hyperthermia,
and Trihexyphenidyl tachycardia, mydriasis, dry mouth, urinary
medications Diphenhydramine retention, altered mental status, hallucinations,
with Biperiden, Procyclidine aggression, seizures, coma, death
anticholinergic Jimson weed
adverse effects Tricyclic
antidepressants
Antipsychotics
Opiates Heroin, Morphine Euphoria, dysphoria, apathy, itching,
Oxycodone somnolence, anorexia, constipation, nausea,
Hydromorphone,Hydrocodone, vomiting, respiratory supp, arrhythmia, cognitive
Meperidine, Fentanyl deficits, delirium, visual hallucinations, anxiety,
Methadone depression, confusion, coma, seizures, death

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 Toxic : abuse and medications
Etiologies Acute, chronic, low-high dose,
overdose

Subdivision Specific entity Possible clinical features

Sedative- Alprazolam [BZD] Decreased cognition, anterograde amnesia. Paradoxical

hypnotics Lorazepam [BZD] aggression/disinhibition: excitement, mania, violence,
Clonazepam [BZD] irritability, agitation, panic, hyperactivity, paranoia,
Temazepam [BZD] hallucinations, insomnia, delirium, confusion, behavioral
Diazepam [BZD] disturbances, ataxia, dysphoria, crying
Midazolam [BZD]
Triazolam [BZD]
Zolpidem [non-BZD] Hallucinations, sensory distortion, delirium,
panic, amnesia, nocturnal eating, sleep
walking/driving, agitation

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 Toxic : abuse and medications
Etiologies Acute, chronic, low-high dose,
overdose

Subdivision Specific entity Possible clinical features

Corticosteroids Prednisone Depression, mania, paranoid delusions, hallucinations,

Methylprednisolone anxiety, panic, confusion, delirium, suicidal, violence

Anabolic-- Testosterone Psychosis, hypomania, mania, depression, anxiety,

androgenic Methyltestosterone aggression, violence, suicide
steroids Nandrolone

Anti- Amantadine, pergolide, Anxiety, irritability, depression, fatigue, euphoria, visual

Parkinson's apomorphine, lisuride, hallucinations, psychosis, delirium, sleep disturbance,
disease drugs bromocriptine, psychomotor agitation, akathisia, cognitive impairment
ropinirole, cabergoline,
pramipexole

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 Toxic : abuse and medications
Etiologies Acute, chronic, low-high dose,
overdose
Subdivision Specific entity Possible clinical features
Cardiovascular Clonidine, Delirium, anxiety, agitation, hypomania, depression,
drugs sulfonamides, psychosis, dementia, sedation, sleep disturbances,
Thiazides, altered color perception, vertigo, confusion
nitrates/nitrites,
quinidine
Immuno Aspirin, non-steroidal Sleep disorders, fatigue, agitation, anxiety, mood
modulators anti-inflammatory disturbances, hallucinations, psychosis, delirium,
drugs tinnitus, tachypnea, deafness, hyperpyrexia,
headaches, seizures, coma, death
Anti-migraine Sumatriptan Fatigue, anxiety, panic
Serotonergic Fluoxetine, paroxetine, Anxiety, agitation, sex dysfunction, nausea, diarrhea,
antidepressants Citalopram, sertraline, sleep dist, anorexia, weight gain, headaches, tremor,
fluvoxamine,Venlafaxin, dry mouth, diaphoresis, mammoplasia, gynecomastia,
12 duloxetine nausea, serotonin synd
 Toxic : abuse and medications
Etiologies Acute, chronic, low-high dose,
overdose

Subdivision Specific entity Possible clinical features

Atypical Clozapine, olanzapine, Anxiety, weight gain, agranulocytosis, tardive
antipsychotics risperidone, quetiapine, dyskinesia, QTc prolongation, hyperprolactinemia,
aripiprazole, ziprasidone, serotonin syndrome, neuroleptic malignant syndrome,
asenapine, lurasidone EPS, metabolic syndrome, priapism, seizures
Antiepileptic Ethosuximide Anxiety, depression, confusion, psychosis, behavioral
drugs disturbances
Felbamate Anxiety, depression, irritability
Levetiracetam Anxiety, depression, hostility, emotional lability,
psychosis
Antibacterial Penicillins Encephalopathy, irritability, sedation, anxiety,
antimicrobial hallucinations

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 Toxic : abuse and medications
Etiologies Acute, chronic, low-high dose,
overdose

Subdivision Specific entity Possible clinical features

Antiviral Acyclovir, ganciclovir Sleep disturbances, anxiety, mood disorders, psychosis
antimicrobial
Antimalarial Chloroquine, Anxiety, panic, depression, suicidality, hallucinations,
antimicrobial mefloquine, quinine psychosis, vertigo, altered color perception, delirium,
confusion

Antiretroviral Ritonavir, didanosine, Anxiety, agitation, mood disorders, depression, sleep

agents lopinavir + ritonavir, disturbance, confusion, psychosis, lethargy
saquinavir, enfuvirtide
Skeletal Dantrolene Sleep disturbance, anxiety, agitation, psychosis,
muscle Baclofen delirium, mood disturbance
relaxants
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 Toxic : withdrawal states
Etiologies

Subdivision Specific entity

Stimulants Amphetamines,
methylphenidate
Cannabis
Opiates Heroin, morphine oxycodone, hydromorphone, hydrocodone,
meperidine, fentanyl, methadone
Sedative-hypnotics Benzodiazepines
Zolpidem
Barbiturates
Alcohol
Antidepressant SSRIs/SNRIs
discontinuation syndrome

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 Infective / post-infective
Etiologies

Subdivision Specific entity

Viral HIV/AIDS
Herpes simplex encephalitis
West Nile virus, Hepatitis C, Epstein Barr
Mycobacterial Tuberculosis meningitis, Leprosy
Bacterial Meningitis, Brucellosis
Parasitic protozoan Malaria
Spirochete Neurosyphilis, Lyme meningitis
Fungal CNS histoplasmosis
Prion diseases Creutzfeldt-Jakob disease

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 Etiologies

Subdivision Possible clinical features

Hydrocephalus Gait disturbance, incontinence, cognitive impairment,dementia,

Pressure
Normal pressure depression, apathy, personality changes, agitation, aggression,
effects
hallucinations, paranoid delusions, anxiety
HT Malignant HT, drowsiness, seizures, vomiting, visual
encephalopathy disturbances, hemiplegia, cerebral edema, coma, death

Anxiety disorders
Panic disorder with/without Obsessive-compulsive disorder
agoraphobia
Psychiatric
Specific phobias Acute stress disorder
Social phobia Post-traumatic stress disorder
Generalized anxiety disorder Anxiety disorder due to a general medical condition
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 Paraneoplastic, subdiv : limbic encephalitis
• Small cell lung ca
Etiologies
Degenerative
• Alzheimer’s disease
• Frontotemporal dementia (onset younger than
Inflammatory disorder : auto-immune alzheimer;s)

• SLE Vascular
Rheumatoid arthritis • Stroke
• Scleroderma • Subarachnoid hemorrhage
• Vasculitis

Other
Neoplastic : Brain tumor (primary & metastatic)
• Environmental : heavy metals
• L>R for depression • Pain
• R>L for mania • Terminal illness
• Pregnancy / post-pregnancy
• Myasthenia gravis : auto-immune
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 Metabolic : electrolyte imbalance
• Hypokalemia
Etiologies • Hyponatremia
• Hypomagnesemia
Metabolic
• Encephalopathy
• Porphyrias
Metabolic : endocrine • Respiratory compromise
• Diabetes • Mitochondrial
• Hyperthyroidism • Vitamin deficiencies
• Hypothyroidism
Movement disorder
• Hyperparathyroidism
• Hypoparathyroidism • Parkinson’s disease
• Cushing‘s syndrome • Huntington’s disease
• Addison‘s disease • Wilson’s disease
• Pheochromocytoma • Tic
• Hyperprolactinemia Sleep disorder
• Dyssomia
• Parasomnia
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 Etiologies

Congenital Ictal
• Cystic fibrosis • Simple/complex partial seizures with or without
• Turner‘s syndrome secondary generalization
• Sickle cell anemia • Generalized seizures
• Fragile X syndrome • NCSE
• PNES
Traumatic brain
• Focal traumatic brain injury Demyelinating disorders

• Multiple sclerosis

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 Case vignette

F, 64 y.o, Anxious and At age 52 Denied : pre-PD psychiatric

depressed excellent premorbid features depression, mania,
Psychiatric consultation psychiatric history endorsing psychosis, panic attacks,
only excessive worrying and obsessive-compulsive
Diagnosis : Parkinson’s disorder, phobias, impulsive
disease situational anxiety
behaviors, eating disorder,
and/or self-mutilation

Past medical history : Family medical history Since PD diagnosis

pertinent for eye surgery with Grandparent with PD with - Depressive episode
complications and migraines dementia - Decreased energy
- Self-deprecatory thoughts
- Depressed mood
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 Case vignette

Anxiety worsened Treatment : pramipexole Persistent visual illusions

PD symptom severity Noted new onset psychosis and hallucinations
progressed Impulsive gambling Related to PD, PD
“On-off fluctuations” pharmacotherapy, visual
Excessive shopping defects (eye surgery)
“Going off and being frozen”  Pramipexole discontinued

Limited benefit : sertraline, Within several years Summarized :

citalopram, escitalopram, Rapid decline cognitive loss Change in QOL
venlafaxine, duloxetine, due to mediical condition
amoxapine, and bupropion Adjustment disorder
decreased mobility Apprehension

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 Case vignette multiple etiologies

(1) primary (2) neurologic (3) coping with the (4) medication-
psychiatric disorder neurologic disease induced
Illness anxiety

 potential for the development of other neuropsychiatric disorders with PD

and PD pharmacotherapy

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 Thank you
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