Differentials
Your Organizational Guidance
ebpracticenet urges you to prioritize the following organizational guidance:
Diagnostiek van dementie in de huisartsenpraktijkPublished by: ACHG | Expertisecentrum Dementie VlaanderenLast published: 2020Diagnostic de la démence en médecine généralePublished by: ACHG | Expertisecentrum Dementie VlaanderenLast published: 2020Common
Mild cognitive impairment (MCI)
History
activities of daily living intact, functional activities preserved with minimal impairment particularly on complex instrumental activities of daily living
Exam
Folstein MMSE score <24
1st investigation
- Folstein MMSE:
<24
More
Delirium
History
rapid onset, short duration, disturbance of consciousness that often waxes and wanes between agitation and lethargy, hallucinations, visual illusions, possible history of infection, metabolic disturbance, or pharmacologic toxicity
Exam
fever, fluctuating level of cognitive impairment at different hours of the day, inattention, disorganized thinking; physical exam may show deficits congruent with underlying pathology causing the delirium
1st investigation
- CBC:
may be WBC >11 x 10³/microliter or <3 x 10³/microliter
More - metabolic panel:
may be Na >145 mEq/L or <135 mEq/L; K >5.5 mEq/L or <3.5 mEq/L; HCO₃ >30 mEq/L or <22 mEq/L; Cr >1.2 mg/dL; glucose <70 mg/dL (after fasting)
More - chest x-ray:
in presence of pneumonia: consolidation demonstrated
More - urinalysis:
may be positive leukocyte esterase, nitrites
More
Depression
History
persistent dysphoric mood, anhedonia (loss of interest in usual activities), impaired recall with relative sparing of recognition memory, poor concentration, sleep and appetite disturbances, energy loss, psychomotor retardation, feelings of worthlessness and guilt, recurrent thoughts of death
Exam
suicidal ideation, problems with attention, concentration, and recent memory
1st investigation
- clinical diagnosis:
diagnosis is clinical
More - Folstein MMSE:
problems with attention, concentration, recent memory
Other investigations
Alzheimer dementia
History
insidious onset, slow progression, memory loss (affecting recent memory first), disorientation in time and place (may manifest as misplacing items or getting lost), difficulty naming objects or people (proper names and low-frequency words decline first); social withdrawal, paranoia, anxiety
Exam
may be normal, especially in early disease; primitive reflexes may be present, rigidity, bradykinesia, abnormal speech and posture; cognitive deficit on screening test
1st investigation
Other investigations
- EEG:
slowing of background rhythm
More
Vascular dementia
History
abrupt or stepwise change, gradual cognitive decline after one or more cerebrovascular events (e.g., ischemic hemorrhagic strokes), may be incontinent, depression, delusions, may have transient neurologic symptoms (e.g., hemiparesis, aphasia, or sensory deficits)
Exam
may have hemiparesis, asymmetric deep tendon reflexes, unilateral extensor plantar response, visual field deficits, gait abnormalities, hypertension, dysrhythmias (e.g., atrial fibrillation), carotid bruits, congestive heart failure, diabetes, emotional incontinence (excessive mood lability); cognitive decline on screening test
1st investigation
- CT/MRI head:
ischemic infarction, may show hippocampal volume loss
More
Other investigations
Lewy body dementia
History
history of fluctuating cognitive performance, episodes of incoherent speech, variable attention (e.g., well-formed visual hallucinations unrelated to dopaminergic therapy), history of parkinsonism emerging simultaneously with cognitive impairment
Exam
muscle rigidity, stooped posture, cog-wheeling, well-formed visual hallucinations, and cognitive fluctuations
1st investigation
- CT/MRI head:
generalized cortical atrophy typical, although may be mild
More
Uncommon
Amnestic syndromes
History
possible history of alcohol misuse, encephalitis, or head trauma, isolated memory loss without apparent cause
Exam
memory impairment; language and visuospatial ability normal
1st investigation
- CT head:
abnormalities in one or more regions of the brain
More
Other investigations
Aphasia
History
acute onset (hours/days), history of transient ischemic attack or stroke
Exam
inability to comprehend instructions, repeat words or phrases, or to read, sparse verbal output (lesion of dominant hemisphere), fluent verbal output with word substitutions/paraphasias and impaired comprehension (lesion in Wernicke area), anomia (Alzheimer disease or frontal lobe degenerative dementia)
1st investigation
- CT head:
focal or diffuse areas of ischemia
Other investigations
Frontotemporal dementia
History
disinhibition, impulsiveness, social inappropriateness, apathy, withdrawal
Exam
disinhibition, lack of executive function, passivity
1st investigation
- none:
disease can often be recognized clinically before changes on routine imaging are apparent
Other investigations
- CT/MRI head:
visualization of focal atrophy in frontal and temporal lobes
- fluorodeoxyglucose-PET (FDG-PET):
hypometabolism in frontal and temporal lobar regions
- Genetic testing:
typically, mutations in the MAPT, GRN, or C9orf72 genes
More
Parkinson disease
History
shaking, stiffness, slowness or poverty of movement, anxiety, apathy, falls, hypersomnolence, bowel and bladder dysfunction
Exam
tremor at rest, rigidity on passive movement, bradykinesia (slowness of movement), poverty of movement (hypokinesia), orthostatic hypotension, and postural instability
1st investigation
- none:
diagnosis made based on clinical exam findings of resting tremor, bradykinesia, hypokinesia, rigidity
More
Other investigations
Huntington disease
History
progressive involuntary movements, neuropsychiatric disturbances, cognitive impairments (e.g., executive function, immediate memory)
Exam
involuntary movements, executive function deficits, deficits in visuospatial abilities, short-term and long-term memory deficits
1st investigation
- none:
diagnosis made based on clinical exam and family history
Other investigations
- serum genetic testing:
abnormal trinucleotide CAG repeat sequence
More
Brain tumors
History
seizures, headache, mental state changes, hemiparesis
Exam
visual field deficits, hemiparesis, aphasia
1st investigation
- MRI brain:
presence of a lesion
Other investigations
Cushing syndrome
History
sudden onset of central weight gain, oligomenorrhea or amenorrhea, spontaneous ecchymoses, florid complexion, difficulty climbing stairs or rising from a low chair, depression
Exam
thickening of facial fat (moon facies), facial telangiectasias, enlarged dorsocervical fat pad (buffalo hump), hypertension, violaceous striae on the abdomen or proximal extremities, acne, mild hirsutism, central fat deposition
1st investigation
- 24-hour urinary cortisol excretion:
elevated
More
Other investigations
- dexamethasone suppression test:
no suppression of cortisol by low dexamethasone doses
More
Hypopituitarism
History
energy loss, muscle weakness, decreased sweating, anorexia, weight loss or weight gain, abdominal pain, reduction in amount of axillary and pubic hair in women, erectile dysfunction, oligomenorrhea/amenorrhea, breast atrophy, loss of libido, infertility, cold intolerance, dry skin, polyuria, polydipsia, nocturia
Exam
may have increased central adiposity, dry skin, reduced muscle mass and strength, visual field defects, circulatory collapse if acute presentation
1st investigation
- luteinising hormone (LH):
low
- follicle-stimulating hormone (FSH):
low
- thyroid-stimulating hormone (TSH):
low
- free thyroxine (T4) and free triiodothyronine (T3):
low
- basal serum cortisol:
low
Other investigations
- testosterone (in men):
low
- estrogen (in women):
low
More - prolactin:
low
- cortisol and growth hormone reserve:
low
- CBC:
anemia
- metabolic panel:
hyponatremia, hyperkalemia, hypoglycemia
- insulin tolerance test:
reduced growth hormone response
More - urine specific gravity:
low in diabetes insipidus
- water deprivation test:
urine is more dilute after administration of desmopressin
More
Primary hyperparathyroidism
History
fatigue, lethargy, muscle weakness, depression, cognitive impairment, recurrent kidney stones, mental state changes, abdominal pain
Exam
proximal muscle weakness
1st investigation
- serum calcium:
elevated
More - parathyroid hormone (PTH):
elevated
Other investigations
Acute intermittent porphyria
History
severe abdominal pain, muscular weakness, constipation, nausea, vomiting, psychiatric disturbances, dark urine, chest pain, back pain, history of exposure to barbiturates, estrogens, sulfonamides, phenytoin, chloramphenicol, tetracyclines, antihistamines, emotional or physical stress, premenstrual, alcohol, smoking
Exam
sensory neuropathy, peripheral motor neuropathy, absent reflexes, hypertension, coma
Other investigations
Primary hypothyroidism
History
fatigue, cold intolerance, dry skin, hoarse voice, constipation, weight gain, depression, muscle weakness
Exam
dry skin, muscle weakness, bradycardia
1st investigation
- thyroid-stimulating hormone (TSH):
high
- free thyroxine (T4):
low
Other investigations
Hyperthyroidism
History
weight loss, heat intolerance, restlessness, anxiety, diarrhea, bulging eyes, hand tremor
Exam
exophthalmos, clammy skin, tachycardia, goiter, high blood pressure
1st investigation
- thyroid-stimulating hormone (TSH):
low
- free thyroxine (T4):
high
- free triiodothyronine (T3):
high
Other investigations
Wilson disease
History
family history may be positive; symptoms emerging in childhood, adolescence, or early adulthood; tremor, slurred speech, abdominal pain, pruritus, generalized malaise, weakness, weight loss, anorexia, pale stools, dark urine, irritability, depression, easy bruising
Exam
Kayser-Fleischer rings, parkinsonian-like tremor, rigidity, clumsy gait, poor balance, impaired coordination, abnormal postures, repetitive movements, bradykinesia (tongue, lips, and jaw), dysarthria, dysphonia (hoarse voice), inappropriate and uncontrollable grinning (risus sardonicus), drooling, hypermelanotic pigmentation, bruises, signs of dementia and/or psychosis, jaundice, hepatosplenomegaly
1st investigation
- serum liver tests:
may be normal, elevated aspartate aminotransferase, alanine aminotransferase, direct bilirubin; alkaline phosphatase normal or below normal
More - prothrombin time/INR:
may be increased
- CBC:
may be normal; cirrhosis: low platelet count
- abdominal ultrasound:
nonspecific
- serum ceruloplasmin:
decreased
More - 24-hour urinary copper excretion:
elevated
More - slit-lamp ophthalmologic exam:
Kayser-Fleischer rings present in Wilson disease
Vitamin B12 deficiency
History
paresthesias, memory loss, gait disturbances; presence of risk factors: age >65 years, history of gastrectomy or gastric bypass, vegan or strict vegetarian diet, chronic gastrointestinal illness, use of proton-pump inhibitors, H2 receptor antagonists, metformin, anticonvulsants
Exam
ataxia, peripheral neuropathy, decreased vibration sense, positive Romberg test, atrophic glossitis, angular cheilitis
1st investigation
- serum vitamin B12 (cobalamin):
decreased
More
Other investigations
- red cell volume:
elevated
- homocysteine:
elevated
- methylmalonic acid:
elevated
Traumatic brain injury
History
history of head injury, headache, lethargy, loss of consciousness after head injury (subdural hematoma)
Exam
altered level of consciousness, slurred speech, hemiparesis (subdural hematoma)
1st investigation
- CT head:
subdural hematoma
Other investigations
Lyme disease
History
history of tick bite and rash
Exam
erythema migrans, fever, headache, myalgias, fatigue, arthritis or arthralgia, facial palsy, peripheral neuropathy
1st investigation
- enzyme immunoassay (EIA) or immunofluorescence assay (IFA):
positive for antibodies to Borrelia burgdorferi
More
Other investigations
Tuberculosis
History
history of tuberculosis (TB) contact, cough, weight loss, and night sweats in addition to symptoms of meningitis
Exam
may be concomitant signs of TB pneumonia, pleural effusion, in addition to signs of meningitis
1st investigation
- chest x-ray:
may demonstrate atelectasis from airway compression, pleural effusion, consolidation, pulmonary infiltrates, mediastinal or hilar lymphadenopathy, upper zone fibrosis
More - sputum acid-fast bacilli (AFB) smear and culture:
presence of acid-fast bacilli (Ziehl-Neelsen stain) in specimen
More - acid-fast bacilli smear and culture of extrapulmonary biopsy specimen:
positive
More - nucleic acid amplification tests (NAAT):
positive for M tuberculosis
More
Other investigations
- CSF PCR for Mycobacterium tuberculosis:
positive in TB meningitis
- lateral flow urine lipoarabinomannan (LF-LAM) assay:
positive
More
Neurosyphilis
History
high risk behaviors including unprotected sexual activity or illicit drug use; infection with HIV or other sexually transmitted infections; nonspecific symptoms; in secondary syphilis: headache, malaise; in neurosyphilis (any stage): meningism, visual changes, hearing loss, seizures, or cognitive impairment; in tertiary (late) syphilis: behavioral changes, gait impairment, incontinence; in congenital syphilis: mother with history of secondary or tertiary syphilis, skin lesions within first 2 weeks of life, rhinitis
Exam
in primary syphilis: painless genital or oral lesion (chancre), regional lymphadenopathy; in secondary syphilis: rash (often on palms or soles), generalized lymphadenopathy, condylomata lata (usually at sites of skin friction such as perianal and vulval regions and under the breasts), uveitis, patchy alopecia, optic neuritis on fundoscopy exam; in tertiary (late) syphilis: hyporeflexia, anisocoria, cranial neuropathy, motor or sensory deficits with positive Romberg's sign, memory impairment, Argyll Robertson pupils (pupils constrict to accommodate near objects but not to light), locally destructive granulomas (gummas) or glossitis may be present with mucosal atrophy; in congenital syphilis: hepatosplenomegaly; co-infection with HIV may alter the presentation of syphilis
1st investigation
- nontreponemal serology test (e.g., serum rapid plasma reagin [RPR] test or serum venereal disease research laboratory [VDRL] test):
positive
More - manual treponemal serology test (e.g., serum Treponema pallidum particle agglutination [TPPA], serum Treponema pallidum hemagglutination [TPHA], serum fluorescent treponemal antibody absorption [FTA-ABS] test):
positive
More - automated treponemal serology test (e.g., serum treponemal enzyme immunoassay [EIA]):
positive
More - dark-field microscopy of swab from lesion:
coiled spirochete bacterium with a corkscrew appearance and motility
More
Other investigations
- lumbar puncture, cerebrospinal fluid (CSF) analysis:
WBC count >10 cells/mm³; CSF protein >50 mg/dL (0.50 g/L); CSF VDRL positive; CSF TPHA/TPPA/FTA-ABS positive
More - cranial CT/MRI:
generalized cerebral atrophy with ventricular dilation; multiple small infarcts in the basal ganglia; syphilitic cerebral gummas appear as an isodense peripheral mass; may be normal
More
Systemic lupus erythematosus
History
fatigue, fever, arthralgia, photosensitivity, Raynaud phenomenon
Exam
arthritis, butterfly rash, hepatomegaly, splenomegaly, cranial neuropathies, peripheral neuropathy
1st investigation
- antinuclear antibodies (ANA):
positive
More
Other investigations
- anti-dsDNA antibodies:
positive
- anti-Sm and anti-RNP antibodies:
positive
- skin biopsy:
noncaseating granulomas
More
Sjogren syndrome
History
fatigue, dry eyes, dry mouth, blurred vision, difficulty swallowing food
Exam
conjunctivitis, angular cheilitis, parotid and/or submandibular gland enlargement, distal polyneuropathy
1st investigation
- Schirmer test:
reduced tear production
Other investigations
- slit lamp examination:
punctate keratopathy confirms keratoconjunctivitis sicca which indicates a long-standing dry eye
- anti-Ro/SSA and/or anti-La/SSB antibodies:
positive
- skin biopsy:
noncaseating granulomas
More
Sarcoidosis
History
cough, dyspnea on exertion, chest pain, fatigue, anorexia, weight loss, and fever
Exam
erythema nodosum and polyarthralgias
1st investigation
- chest x-ray:
bilateral hilar lymphadenopathy
Other investigations
- skin biopsy:
noncaseating granulomas
More
Drug use
History
use of anticholinergic drugs (e.g., antihistamines, drugs for irritable bowel syndrome); some evidence that androgen deprivation therapy may be associated with an increased risk of dementia, but this remains controversial and further investigation is required.
Exam
may have chronic urticaria (requiring antihistamines)
1st investigation
- anticholinergic levels:
therapeutic range/high
- antihistamine levels:
therapeutic range/high
Other investigations
Toxin-induced
History
ingestion of alcohol, exposure to heavy metals (e.g., arsenic, lead, mercury, carbon monoxide, and cyanide)
Exam
tremor, hepatomegaly, gynecomastia (in alcohol misuse), abdominal pain, mood disorder (in lead poisoning)
1st investigation
- urine heavy metal screen:
elevated levels of heavy metal
- gamma-glutamyltransferase (GGT):
elevated in alcohol misuse
Other investigations
Normal pressure hydrocephalus
History
headache, balance disturbances, urinary incontinence
Exam
unstable gait, slow movement, wide-based stance
1st investigation
- CT head:
hydrocephalus
- lumbar puncture:
normal, opening pressure 70 to 250 mm H₂O
More
Other investigations
Creutzfeldt-Jakob disease
History
rapidly progressive dementia, characterized by memory loss, personality changes, and hallucinations
Exam
visual impairment, speech impairment, development of akinetic mutism, myoclonus, ataxia, and seizures
1st investigation
- EEG:
characteristic triphasic spikes
Other investigations
- CSF analysis (lumbar puncture):
14-3-3 protein detected; total tau (T-tau) protein elevated; neuron-specific enolase elevated
- MRI brain:
often demonstrates hyperintensity in the cerebral cortex (cortical ribboning), basal ganglia (caudate and putamen), and thalamus on diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) sequences, and hypointensity (restricted diffusion) on attenuated diffusion coefficient map (ADC) sequences
- MRI brain using diffusion-weighted imaging:
cortical and subcortical hyperintensities
More - brain biopsy:
dead neurons and abnormal prion proteins; brain tissues have many holes giving the brain a spongy appearance
More
Use of this content is subject to our disclaimer