A 53-year-old woman was referred to our department due to frequent falls and imbalance starting one month ago. The family reported significant behavioral changes and memory impairment over the last four months. She had hypertension and dyslipidemia under treatment. Alcohol and tobacco consumption were denied. The patient mentioned episodes of rhinorrhea for the last four years, noticed when moving from a supine to standing position or while bending, without a history of trauma. Clinical examination revealed increased tendon reflexes and increased symmetrical muscle tone in all limbs, cogwheel rigidity in the left hand, cerebellar ataxia in all limbs, serious trunk titubation and head tremor and serious difficulty walking a few steps unassisted. Cognitive function examination showed memory impairment, loss of language comprehension and behavioral disorders such as apathy and disinhibition. A brain MRI conducted prior to her admission revealed cerebral small-vessel disease and inflammatory material in the sphenoid sinus. At the clinic, routine blood test, HIV and H1N1, B₁₂ vitamin, thyroid hormones, autoantibodies, EEG and CSF examinations were conducted. Positive antinuclear autoantibodies (ANA) at a small titer, diffuse slowing on EEG and mildly elevated protein (68 mg/dl) in CSF were the only remarkable findings. The reported nontraumatic rhinorrhea by the patient is an alarming symptom and should also be confirmed. A complementary head CT to examine rhinorrhea revealed a dural defect (Figure 1A, B). Additionally, the fluid was tested for β2-transferrin, a highly specific protein for CSF, and it was positive. Within a few days, the patient developed orofacial myorhythmia, upper limb choreoathetosis and sleep disturbances, and her cognitive state deteriorated. A second brain MRI was conducted and revealed high-intensity signal in T2, Fluid-Attenuated Inversion Recovery (FLAIR) and Diffusion-Weighted Imaging (DWI) in the caudate nucleus and putamen (Figure 2). The patient’s CSF was sent for the RT-QuIC test, which was positive. These findings, along with positive RT-QuiC test, indicate probable Creutzfeldt–Jakob disease (CJD). No other treatment effort has been done since no treatment is known to increase survival in CJD patients so far. The patient soon became mute and passed away approximately a month after the diagnosis.

Figure 1.

(A) Sagittal head CT. (B) Axial head CT. Dural defect and inflammatory material occupying the sphenoid sinus are present in both images, which confirms the suspected rhinorrhea.

Figure 1 Long description

Panel A: A sagittal head CT scan showing a side view of the head. The scan highlights a dural defect and inflammatory material occupying the sphenoid sinus. An arrow points to a specific area of interest. Panel B: An axial head CT scan showing a horizontal cross-section of the head. Similar to Panel A, this scan also shows a dural defect and inflammatory material in the sphenoid sinus.

Figure 2.

Brain MRI axial FLAIR. High-intensity signal is present in the caudate nucleus and putamen. These findings are compatible with Creutzfeldt–Jakob disease.

The differential diagnosis of rapidly progressive cognitive decline mainly consists of prion diseases, rapidly progressive subtypes of neurodegenerative diseases (e.g., rapidly progressive Alzheimer’s Disease (AD), inflammatory etiologies (autoimmune, viral or bacterial encephalitis), metabolic or toxic causes (such as Wernicke–Korsakoff syndrome, hepatic encephalopathy), neurovascular causes (recurrent stroke, vasculitis) and other secondary complications of concomitant pathologies.^{Reference Day1} However, our patient had confirmed nontraumatic CSF rhinorrhea. This remarkable symptom added a rare entity, brain sagging dementia (BSD), high in our differential diagnosis. It is important to primarily investigate BSD when it is suspected in a patient with progressive cognitive decline, as it consists of an uncommon but reversible cause.

Brain sagging dementia mimics behavioral variant frontotemporal dementia (FTD) and is caused by spontaneous intracranial hypotension. Clinical presentations vary from completely asymptomatic or mild postural headache to the other end of the spectrum with FTD, extrapyramidal syndromes with choreiform movement disorders and coma.^{Reference Lashkarivand and Eide2} Our patient met several criteria for BSD: her age (<65 years old), clinical presentation of FTD with behavioral changes that developed insidiously during the last four months, the lack of frontotemporal brain atrophy on MRI, the choreiform movements she developed and the confirmed CSF leakage with beta-2 transferrin without a history of trauma were consistent with the entity. However, our patient lacked a headache, which is observed in the vast majority of patients with BSD, and most importantly, no signs of brain sagging were observed in the MRI; this automatically excluded this diagnosis. Pachymeningeal thickening and enhancement, subdural effusion, pituitary hyperemia, venous engorgement, descent of the brainstem and cerebellar tonsils, posterior fossa crowding, flattening of the anterior pons and a decreased angle between the vein of Galen and straight sinus measured in a midline sagittal section are supportive imaging findings for BSD, and they are required to consider it.^{Reference Lashkarivand and Eide2,Reference Mulroy, Caldwell, Anderson and Snow3}

After further investigations, our patient was finally diagnosed with probable CJD. CJD is a transmissible spongiform encephalopathy with an estimated incidence of one case per million annually. The disease is classified into three broad categories: sporadic, genetic and infectious.^{Reference Uttley, Carroll, Wong, Hilton and Stevenson4} CJD may be rare in the general population but is of major importance in the context of rapidly progressive dementia syndrome.^{Reference Day1}

According to the current diagnostic criteria, a rapidly progressive cognitive impairment is required to consider the possibility of CJD. In addition, myoclonus, visual or cerebellar disturbance, pyramidal or extrapyramidal signs and akinetic mutism are regarded as the main secondary clinical manifestations of the entity. In our case, both primary and two of the secondary criteria (cerebellar disturbance, extrapyramidal signs) were present at the patient’s arrival. The patient’s development of akinetic mutism together with the typical MRI findings (signal abnormalities in DWI and/or FLAIR sequences primarily affecting the temporal, parietal and occipital cortices, as well as the basal ganglia, particularly the putamen and caudate nucleus) and the positive RT-QuIC test during the course of our investigation led to the conclusion of probable CJD. A definite CJD diagnosis can only be confirmed after a brain biopsy or autopsy.^{Reference Hermann, Brian and Brandel5}