Differentials
Common
Ischemic stroke
History
sudden onset difficulty speaking or understanding words and/or sentences, often with impaired reading and writing or trouble using the right hand; rarely associated with pain or systemic symptoms; patient may be unaware of the deficit
Exam
Broca aphasia: nonfluent speech and repetition with relatively spared comprehension often associated with right-central facial weakness (lower facial droop and intact reflexive smile) and right arm weakness; Wernicke aphasia: fluent jargon speech and repetition with homonymous right upper quadrantanopsia or hemianopsia; global aphasia: muteness with poor word comprehension and right hemiplegia involving the face, arm, and usually leg; anomic aphasia: poor word retrieval only
1st investigation
Other investigations
- CT angiography of the circle of Willis:
might show occlusion of a vessel as the cause of stroke
More - magnetic resonance angiogram (MRA) of the circle of Willis:
may show occlusion of a vessel as the cause of stroke
- echocardiogram:
may reveal a cardioembolic source of stroke (e.g., thrombus, vegetations on heart valves, akinetic wall; large patent foramen ovale with associated mural aneurysm and right-to-left shunt)
More - bubble study:
saline contrast material useful in diagnosis of patent foramen ovale
- carotid Doppler:
may reveal stenosis of the common carotid or internal carotid artery on the side of the dominant hemisphere (usually left)
More - MRA of the neck:
may reveal carotid stenosis
Intracerebral hemorrhage
History
sudden onset difficulty speaking or understanding words and/or sentences, often with impaired reading and writing, trouble using the right hand, or right visual field deficit; presentation similar to ischemic stroke except more commonly associated with headache, nausea, or reduced level of consciousness at onset
Exam
Broca aphasia: nonfluent speech and repetition, relatively spared comprehension often associated with right central facial weakness (lower facial droop with intact reflexive smile) and right arm weakness; Wernicke aphasia: fluent jargon speech and repetition with homonymous right upper quadrantanopsia or hemianopsia; global aphasia: muteness with poor word comprehension and right hemiplegia involving the face, arm, and usually leg
1st investigation
- CT head (noncontrast):
hemorrhage (bright), usually in left cortex, thalamus, or basal ganglia
- MRI head with gradient echo:
hemorrhage (black on gradient echo), usually in left cortex, thalamus, or basal ganglia
More - chemistry panel:
normal
More - CBC:
normal
More - PT and activated PTT:
usually normal
More - ECG:
signs of myocardial ischemia, cerebral T waves
More
Alzheimer disease
History
causes logopenic progressive aphasia; progressive impairment in older individuals with deficit in recent memory, learning, and word retrieval, usually with little insight
Exam
impaired learning and recall, impaired naming, impaired executive function
1st investigation
- none:
diagnosis is clinical
More
Other investigations
- neuropsychological testing:
impairment in the ability to recall recent events and people
More - MRI or CT head:
bilateral temporal and parietal atrophy
More - single photon emission computed tomography head:
bilateral temporal and parietal hypoperfusion
- PET of the head:
bilateral temporal and parietal hypometabolism
More - lumbar puncture:
tau/A-beta42 ratio: elevated
More
Traumatic head injury
History
history of trauma, often accompanied by change in level of consciousness or headache and dizziness
Exam
external evidence of trauma: bruising, bleeding, raccoon eyes, fractures, watery nasal discharge (cerebrospinal fluid rhinorrhea)
1st investigation
- CT head:
intracranial hemorrhage (epidural, subdural, and/or intracerebral), skull fracture and/or contusion
Other investigations
Uncommon
Subdural hematoma
History
typically history of head trauma or fall; may occur without known trauma in elderly and/or in presence of anticoagulation
Exam
normal or focal neurologic signs; aphasia is rare
1st investigation
- CT head:
blood (old and/or new) in subdural space
Other investigations
Subarachnoid hemorrhage
History
severe headache ("worst headache of life"); associated nausea, vomiting, and stiff neck, with or without focal neurologic deficits
Exam
nuchal rigidity or focal neurologic signs may be present
1st investigation
- CT head:
blood in the subarachnoid space
More
Other investigations
- lumbar puncture:
erythrocytosis or xanthochromia
Migraine
History
a common condition but a rare cause of aphasia; severe, usually unilateral, headaches; associated nausea, vomiting, photophobia, phonophobia, scalp sensitivity, visual disturbance, and/or focal neurologic deficits
Exam
normal; focal neurologic signs such as aphasia, hemiplegia, visual field deficit, or anisocoria during episodes
1st investigation
- CT head:
normal
More
Other investigations
- MRI brain:
normal or 1 or more punctate white matter changes
More
Herpes encephalitis
History
recent-onset fever, nausea, vomiting, headache; associated with confused speech and poor comprehension
Exam
tachycardia, impaired speech and comprehension; altered memory and behavior
1st investigation
- CT head:
contrast-enhancing lesion, sometimes with mass effect, or normal
Other investigations
- lumbar puncture:
mononuclear leukocytosis; positive herpes simplex virus polymerase chain reaction (may be negative acutely); positive herpes simplex virus IgM
More - MRI head with and without contrast:
well-defined signal abnormality with contrast enhancement, often surrounded by vasogenic edema
- electroencephalogram:
periodic lateralized epileptiform discharges or focal temporal slowing
West Nile encephalitis
History
recent-onset fever, nausea, vomiting, headache; may be associated with focal neurologic deficits such as impaired speech and poor comprehension
Exam
tachycardia, impaired speech and comprehension; altered memory and behavior
1st investigation
- CT head:
contrast-enhancing lesion, sometimes with mass effect or normal
Other investigations
- lumbar puncture:
mononuclear leukocytosis; positive West Nile polymerase chain reaction (may be negative acutely)
More - MRI head with and without contrast:
well-defined signal abnormality with contrast enhancement, often surrounded by vasogenic edema
- electroencephalogram:
periodic lateralized epileptiform discharges or focal temporal slowing
Bacterial infection/abscess
History
recent-onset fever, nausea, vomiting, headache
Exam
tachycardia, focal neurologic signs, nuchal rigidity
1st investigation
- CBC:
leukocytosis
- CT head:
contrast-enhancing lesion, sometimes with mass effect or normal
Other investigations
- lumbar puncture:
polynuclear leukocytosis (early); positive Gram stain or cultures for organism
More - MRI head with and without contrast:
well-defined signal abnormality with contrast enhancement, often surrounded by vasogenic edema
- electroencephalogram:
focal slowing or seizure discharges
Fungal abscess
History
recent-onset fever, nausea, vomiting, headache
Exam
tachycardia, focal neurologic signs and nuchal rigidity
1st investigation
- CBC:
leukocytosis
- CT head:
contrast-enhancing lesion, sometimes with mass effect
Other investigations
- lumbar puncture:
high protein, low glucose, and often increased white blood cells; positive Gram stain or cultures for organism
More - MRI head with and without contrast:
well-defined signal abnormality with contrast enhancement, often surrounded by vasogenic edema
- electroencephalogram:
focal slowing or seizure discharges
Prion disease
History
rapidly progressive impairment in language, attention, recent memory, visuospatial skills, or other domains of cognition; often associated with abnormal movements or gait; isolated aphasia is an atypical presenting feature
Exam
impaired language, attention, recall, visuospatial skills, calculation, and/or executive function; startle myoclonus; spasticity or rigidity; hyperreflexia; Babinski and Hoffman signs (unilateral or bilateral)
1st investigation
- MRI head with diffusion weighted imaging (DWI):
bilateral or unilateral faint cortical ribbon and/or signal changes in basal ganglia on DWI
More
Toxoplasmosis
History
recent-onset fever, nausea, vomiting, headache; key risk factors include immune suppression, infection during pregnancy, exposure to cat feces, ingesting raw or undercooked meat, and residence in a high-risk area
Exam
tachycardia, focal neurologic signs, and nuchal rigidity
1st investigation
- CBC:
leukocytosis
- CT head:
contrast-enhancing lesion, sometimes with mass effect
Other investigations
- lumbar puncture:
high protein, low glucose, and often increased white blood cells; positive Gram stain or cultures for organism
More - MRI head with and without contrast:
well-defined signal abnormality with contrast enhancement, often surrounded by vasogenic edema
- electroencephalogram:
focal slowing or seizure discharges
- serum anti-Toxoplasma IgM:
detectable
More
Lyme disease
History
a common condition but a rare cause of aphasia; possibly a preceding rash or target lesion (erythema migrans) or known bite of deer tick; flulike illness with fluctuating fever and chills; later may experience joint pain, painful neuropathy, and/or confusion and cognitive deficits (and occasionally aphasia)
Exam
encephalopathy, with occasional focal neurologic deficits; may have cardiac arrhythmia and facial nerve paralysis
1st investigation
- CBC:
leukocytosis
- serum Lyme titer:
first test for both IgM and IgG antibodies using enzyme-linked immunosorbent assay (ELISA); if the ELISA is positive or equivocal, add an immunoblot test; diagnose Lyme disease in people with symptoms of Lyme disease and a positive immunoblot test[24]
Other investigations
- lumbar puncture:
positive Lyme titer, may have pleocytosis or high protein
- MRI:
focal, often deep, enhancing lesions
Nonfluent/agrammatic-variant primary progressive aphasia (PPA)
History
progressive difficulty speaking, without difficulty understanding; ability to recall recent events and people; independence in daily activities
Exam
nonfluent speech and repetition, relatively spared comprehension; often associated with right central facial weakness (lower facial droop with intact reflexive smile) and right arm apraxia
1st investigation
- MRI head:
focal left posterior frontal and insular atrophy
More
Other investigations
- single photon emission computed tomography head:
focal left posterior frontal hypoperfusion
- PET of the head:
focal left posterior frontal and insular hypometabolism
Semantic-variant PPA
History
progressive difficulty speaking meaningfully and difficulty understanding; ability to recall recent events and people; independence in daily activities
Exam
fluent, jargon speech and repetition, poor word comprehension, often with poor object recognition but spared speech articulation
1st investigation
- MRI head:
focal left anterior and inferior temporal atrophy
More
Other investigations
- single photon emission computed tomography head:
focal left anterior and inferior temporal hypoperfusion
- PET of the head:
focal anterior and inferior temporal hypometabolism
Logopenic-variant PPA
History
progressive difficulty speaking, with or without difficulty understanding; ability to recall recent events and people; independence in daily activities
Exam
poor word retrieval and repetition with normal word comprehension and speech articulation
1st investigation
- MRI head:
focal left superior temporal and/or parietal atrophy
More
Other investigations
- single photon emission computed tomography head:
focal left superior temporal and/or parietal hypoperfusion
- PET of the head:
focal left superior temporal and/or parietal hypometabolism
Aphasia dysarthria motor neuron disease (amyotrophic lateral sclerosis [ALS]-frontotemporal degeneration)
History
progressive weakness and muscle twitching in 2 or more limbs, slurred speech, language impairment; may be with or without change in personality and behavior (disinhibited, obsessive compulsive, apathetic, impulsive) or mood (anxiety, depression, and/or mania)
Exam
upper motor neuron signs (Babinski or Hoffman sign, hyperreflexia) and lower motor neuron signs (focal weakness, fasciculations), in addition to language and cognitive deficits, dysarthria
1st investigation
- electromyogram (EMG):
increased motor unit potentials; compound muscle action potentials may be normal (initially) or increased (late in disease); sensory nerve action potentials should be normal
More
Other investigations
- nerve conduction velocity tests:
are often done with EMG to rule out other causes of weakness such as Guillain-Barre syndrome
- MRI brain:
asymmetric frontal or temporal atrophy, mostly on the left
- single photon emission computed tomography head:
focal left frontal or temporal hypoperfusion
- PET of the head:
focal left frontal or temporal hypoperfusion
Primary brain tumor
History
recent history of morning headaches, with or without nausea, vomiting, and/or weight loss; associated problems speaking and understanding language
Exam
papilledema, impaired speech and/or impaired comprehension, often with seizures
1st investigation
- MRI head with and without contrast:
well-defined signal abnormality with contrast enhancement, often surrounded by vasogenic edema
Other investigations
- brain biopsy:
pathology of primary central nervous system tumor
Brain metastases
History
recent history of morning headaches, with or without nausea, vomiting, and/or weight loss; associated problems speaking and understanding language; possible past history of breast or lung cancer or melanoma
Exam
papilledema, impaired speech and/or impaired comprehension, often with seizures
1st investigation
- MRI head with and without contrast:
well-defined signal abnormality with contrast enhancement, often surrounded by vasogenic edema
Other investigations
- brain biopsy:
pathology of primary tumor
Multiple sclerosis
History
a common condition but a rare cause of aphasia; multiple neurologic deficits (e.g., optic nerve, spinal cord, brain stem, different sides of the supratentorial brain, cerebellum) typically occurring at different times; monocular visual loss; numbness, weakness, poor coordination, fatigue, or gait impairment; cognitive or language deficits; symptoms typically last days to weeks or longer and are exacerbated by heat
Exam
difficulty with word retrieval, reading, spelling, memory, or other higher level cognitive skills; unilateral optic disc edema; intraocular ophthalmoplegia; weakness or spasticity in 1 or more limbs; ataxia, hyperreflexia, or impaired sensory thresholds in 1 or more limbs; often only one or two of these are present
1st investigation
- MRI of the brain and spine with and without contrast:
scattered white matter changes, some of which show contrast enhancement, often abutting the corpus callosum
More
Sarcoidosis
History
subacute onset of bilateral facial nerve palsy, uveitis, and parotitis is a common presentation of neurosarcoidosis; may later develop focal neurologic deficits such as aphasia due to brain lesions
Exam
bilateral cranial nerve VII (CN VII) weakness, uveitis, parotitis, and/or focal neurologic signs (cognitive or language deficits, hyperreflexia, hemiparesis)
1st investigation
- chest x-ray:
hilar lymphadenopathy or normal
Other investigations
Acute disseminated encephalomyelitis
History
rapidly progressive impairment in language, attention, recent memory, visuospatial skills, or other domains of cognition; often associated with abnormal movements or gait
Exam
impaired language, attention, recall, visuospatial skills, calculation, and/or executive function; spasticity; hyperreflexia; Babinski and Hoffman signs (unilateral or bilateral)
1st investigation
- MRI brain:
focal or diffuse white matter changes with some areas of enhancement
Other investigations
Seizure
History
a common condition but a rare cause of aphasia; recurrent episodes of sudden-onset neurologic deficits (e.g., aphasia), usually associated with focal, rhythmic jerking, which may become bilateral
Exam
normal or residual neurologic deficits (e.g., aphasia and right hemiplegia)
1st investigation
- electroencephalogram (EEG):
focal seizure discharges, sharp waves
More
Other investigations
- prolonged EEG and video monitoring:
focal seizure activity during episodes
- MRI head:
may show mass or other lesion as cause of seizures with aphasia
Conversion disorder
History
sudden-onset bizarre speech or mutism, psychiatric or environmental vulnerabilities (e.g., recent major life event)
Exam
normal examination except language production
1st investigation
- none:
diagnosis is clinical
Other investigations
- observation:
often will reveal normal language in supportive environment
- MRI head:
normal
More - electroencephalogram:
normal
- lumbar puncture:
normal
Wernicke encephalopathy (thiamine deficiency)
History
most common in people with nutritional deficiency (including people with alcohol use disorder) or anorexia nervosa, or in professions where excess weight discouraged (e.g., jockeys, ballerinas, models); confusion, confabulation, impaired coordination, double vision
Exam
jargon speech, poor comprehension and attention, nystagmus, ophthalmoplegia, ataxia
1st investigation
- serum thiamine level:
low
More
Other investigations
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