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
  • CT head (noncontrast):

    normal initially; effectively excludes intracranial hemorrhage

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  • MRI head with diffusion weighted imaging:

    bright area corresponding to infarct; apparent diffusion coefficient map shows dark area in the same location

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  • serum glucose:

    normal or elevated

Other investigations
  • CT angiography of the circle of Willis:

    might show occlusion of a vessel as the cause of stroke

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  • 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)

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  • 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)

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  • 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

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  • chemistry panel:

    normal

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  • CBC:

    normal

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  • PT and activated PTT:

    usually normal

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  • ECG:

    signs of myocardial ischemia, cerebral T waves

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Other investigations
  • CT angiography:

    may show aneurysm or AVM

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  • MR angiography:

    may show aneurysm or AVM

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  • conventional (invasive) angiography:

    may show aneurysm or AVM

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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

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Other investigations
  • neuropsychological testing:

    impairment in the ability to recall recent events and people

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  • MRI or CT head:

    bilateral temporal and parietal atrophy

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  • single photon emission computed tomography head:

    bilateral temporal and parietal hypoperfusion

  • PET of the head:

    bilateral temporal and parietal hypometabolism

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  • lumbar puncture:

    tau/A-beta42 ratio: elevated

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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

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      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

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      Other investigations
      • MRI brain:

        normal or 1 or more punctate white matter changes

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      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

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      • 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

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      • 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

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      • 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

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      Other investigations
      • lumbar puncture:

        normal cells and protein; 14-3-3 protein positive

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      • electroencephalogram:

        generalised slowing, focal or diffuse, and periodic polyspike-wave complexes and sharp waves

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      • brain biopsy:

        spongiform encephalitis, mutant prion protein

      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

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      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
      Other investigations
      • lumbar puncture:

        1 or more oligoclonal bands

        More
      • visual evoked responses and auditory evoked responses:

        delay in visual or auditory pathways caused by demyelination of white matter tracts

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      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
      • CT chest:

        hilar lymphadenopathy

      • biopsy of lymph node or other lesion:

        noncaseating granulomas

      • MRI of brain and spine with and without contrast:

        scattered white matter changes, some of which show contrast enhancement

        More
      • lumbar puncture:

        may have 1 or more oligoclonal bands; may have elevated ACE level

        More

      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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