MKSAP Quiz: 1-month history of diminished concentration
A 57-year-old woman is hospitalized with a 1-month history of diminished concentration, memory, and judgment, with recent mental status fluctuations and gait disorder. Medical history is remarkable for hypertension. After a physical exam, lab studies, and brain MRI, what is the most likely diagnosis?
A 57-year-old woman is hospitalized with a 1-month history of diminished concentration, memory, and judgment, with recent mental status fluctuations and gait disorder. Medical history is remarkable for hypertension. Medications are enalapril and hydrochlorothiazide.
On physical examination, vital signs are normal. She is somnolent but responds to verbal commands. The neck is supple. Deep-tendon reflexes are increased in the upper extremities and decreased in the lower extremities. Movement of the extremities is associated with myoclonus. The remainder of the examination is normal.
Complete blood count, comprehensive metabolic profile, thyroid studies, and vitamin B12 measurements are normal.
Lumbar puncture:
| Opening pressure | 70 mm H2O |
| Leukocyte count | 4/µL (4 × 106/L) |
| Erythrocyte count | 5/µL (5 × 106/L) |
| Glucose | 108 mg/dL (6 mmol/L) |
| Protein | 57 mg/dL (570 mg/L) |
Gram stain of cerebrospinal fluid is negative. Polymerase chain reaction of cerebrospinal fluid for herpes simplex virus is negative.
Brain MRI shows abnormally increased T2 and FLAIR signal intensity in the putamen and head of the caudate.
Which of the following is the most likely diagnosis?
A. Cryptococcal meningoencephalitis
B. Sporadic Creutzfeldt-Jakob disease
C. Tuberculous meningitis
D. Vascular neurocognitive disorder
MKSAP Answer and Critique
The correct answer is B. Sporadic Creutzfeldt-Jakob disease. This content is available to MKSAP 18 subscribers as Question 86 in the Infectious Disease section. More information about MKSAP is available online.
This patient most likely has sporadic Creutzfeldt-Jakob disease (sCJD). This is the most common form of prion disease and has no evidence of environmental risk factors. Involvement of several neurologic systems and a rapid onset of apparent dementia are classic manifestations of prion disease. On physical examination, ataxia, myoclonus, and a rapidly progressive dementia are present. MRI abnormalities are not specific for sCJD and vary with the clinical syndrome. Patients with increased T2 signal in the caudate and putamen are more likely to have early dementia and shorter survival. No simple, noninvasive assay is available to diagnose sCJD; however, the presence of T-tau or 14-3-3 protein in cerebrospinal fluid (CSF) can be suggestive. The definitive diagnostic test is a brain biopsy demonstrating widespread spongiform changes with gliosis. No definitive treatment exists for any prion disease, and most are rapidly fatal.
Cryptococcal meningitis may present initially with altered mentation. Cryptococcal meningitis can be seen in apparently immunocompetent persons; however, it is likely that most patients who develop this infection have some underlying immune deficiency. Lumbar puncture may show a high opening pressure, and the CSF typically shows a lymphocytic pleocytosis. The patient's findings are not compatible with this diagnosis.
Tuberculous meningitis may present with waxing and waning mental status changes. However, the CSF in tuberculous meningitis frequently shows high protein (>500 mg/dL [5000 mg/L]) and low glucose (<40 mg/dL [2.22 mmol/L]) levels. Additionally, MRI may reveal basilar pachymeningitis and occasional tuberculomas, which are not seen in this patient.
Vascular neurocognitive disorder (VND) is the term now used to describe cognitive impairment of any degree resulting from cerebrovascular disease. The diagnosis is made when neuroimaging or clinical history reveals evidence of a stroke or subclinical cerebrovascular disease that is responsible for impairment of at least one cognitive domain. The absence of infarcts on MRI and rapid progression of this patient's symptoms are not compatible with VND.
Key Point
- Sporadic Creutzfeldt-Jakob disease is the most common form of prion disease, involving several neurologic systems and rapid progression of apparent dementia.