RIVIERA BEACH, FLORIDA—Rapidly progressive dementia may result from a treatable condition that is mistaken for Creutzfeldt–Jakob disease (CJD), said Michael Geschwind, MD, PhD, at the 41st Annual Meeting of the Southern Clinical Neurological Society. Treatable conditions that could cause dementia include toxic-metabolic syndromes, antibody-mediated autoimmune disorders, tumors, and infections. With effective treatment, patients often improve or regain their cognitive function.

Dr. Geschwind, a neurologist at the University of California, San Francisco, Memory and Aging Center, discussed a study in which he and colleagues identified 178 patients referred to their center whose referral diagnoses of CJD proved to be incorrect. Almost one-quarter of the individuals had treatable autoimmune dementias. Other patients in the group had treatable infections, psychiatric disorders, or malignancy. “These patients were essentially given death sentences, and their diagnostic workup had stopped,” said Dr. Geschwind.

A Mnemonic Device May Aid Diagnosis
The mnemonic device “VITAMINS” can help neurologists diagnose patients with dementia whose presentation or history is unusual, said Dr. Geschwind. The letters of the mnemonic are intended to remind clinicians of vascular factors (eg, strokes or vasculitis); infections; toxic-metabolic syndromes; autoimmune disease; metastases or neoplasms; iatrogenic factors; neurodegenerative diseases; and seizures, systemic problems (eg, sarcoid or Behçet’s syndrome), or structural problems (e.g., spontaneous intracranial hypotension or hydrocephalus). With the exception of neurodegenerative diseases, these items are common, treatable causes of dementia.

Various tests may help confirm that a patient’s dementia arises from a treatable cause. “I usually suggest to have at least one MRI with contrast and try to acquire axial and coronal FLAIR, T2, diffusion-weighted imaging (DWI), attenuation diffusion coefficient (ADC) map, and hemosiderin (eg, gradient echo or susceptibility-weighted) sequences,” said Dr. Geschwind. Hemosiderin sequences can help neurologists look for cerebral amyloid angiopathy, which is important because some patients with this condition respond well to steroids. When getting CSF, physicians should consider checking a patient’s IgG index and analyzing oligoclonal bands. For a patient with a rapid case of dementia, it may be advisable to send CSF samples to the National Prion Disease Pathology Surveillance Center to test for 14-3-3 protein and total tau, as well as to Mayo Laboratories for neuron-specific enolase. These tests can confirm the occurrence of rapid neuronal injury and support a medical history but may not confirm or rule out a diagnosis of CJD. These CSF tests are not as specific for CJD as DWI/ADC MRI, however. A newer CSF test called RT-QuIC is a more specific test for prion disease than the other CSF tests but is not as sensitive as MRI.

“If the diagnosis for a rapidly progressive dementia isn’t clear, get body imaging with contrast,” said Dr. Geschwind. “I always check for reversible conditions.”

Lymphoma and CJD May Cause Similar Cognitive Symptoms
Wernicke’s encephalopathy and CJD can result in similar DWI MRI findings in the thalamus, and the former disease sometimes is mistaken for the latter. A patient with suspected CJD recently was referred to Dr. Geschwind for a second opinion. The patient’s MRI with restricted diffusion in the thalamic mammillary bodies and clinical history of poor diet and weight loss suggested a diagnosis of thiamine deficiency. When the patient died, an autopsy confirmed the diagnosis of Wernicke’s encephalopathy. Had the diagnosis been made earlier, the patient’s death may have been prevented, said Dr. Geschwind.

A 67-year-old woman with rapidly progressive dementia was referred to Dr. Geschwind for a treatment trial for CJD. The woman’s symptoms included changes in personality, language problems, worsening memory, ataxia, general hemiparesis, and mild contrast enhancement on MRI. Dr. Geschwind suspected that the patient had a tumor or infection. The patient’s angiogram was positive, and Dr. Geschwind and colleagues began serial checks of the patient’s lactate dehydrogenase level. “It began to markedly go up; that’s often a marker for lymphomas,” said Dr. Geschwind. “We did the brain biopsy, and sure enough, it showed intravascular lymphoma. This was years ago. The patient’s doing great.”

During the past year, a 45-year-old fireman presented to Dr. Geschwind’s center with apparent behavioral variant frontotemporal dementia. The patient, whom acquaintances had described as decent and tactful, had become aggressive, rude, and compulsive over several years, beginning after he volunteered for cleanup in the aftermath of Hurricane Katrina. He developed stereotypies such as head scratching, hand tapping, and pacing. In addition, his food preferences changed, he lost weight, and he developed dysphagia. MRI revealed that the patient’s brainstem was compressed, that his cerebellum was sagging and there was enhancement of the dura.

“This is an entity called spontaneous intracranial hypotension, causing a frontotemporal syndrome or CSF hypovolemia,” said Dr. Geschwind. The condition often results from a dural CSF leak, he added. After Dr. Geschwind’s colleagues performed a myelogram, found the CSF leak, and administered a blood patch, the patient improved dramatically.

—Erik Greb

Rapidly Progressive Dementia May Have a Treatable Cause