A 75-yr-old right-handed woman presented with a 8 month history of neuropsychiatric symptoms and progressive dementia. Her family described that her symptoms started with severe depression, including suicidal ideation. She became frequently irritable and would not go outside for fear of getting hit by a car. Further, she suffered from delusions of people on the television staring at her and visual hallucinations such as a thief writing letters on the wall with black paint. Antidepressants did not help her symptoms.
Approximately 4 months before her admittance to the hospital, she developed memory problems. She asked for the same items repeatedly. She did not remember who she was speaking with on the phone, making transitions in conversation as if she had suddenly spoken with a person other than the one she was actually speaking with. Her memory gradually worsened, which led to a diagnosis of dementia at a local psychiatric clinic. Within 2 months, her cognitive decline and behavioral changes were more prominent. She had difficulty finding the bathroom at home and recognizing her family. Her behaviors were stereotypic and disinhibited, such as walking in and out of rooms repeatedly and walking around her house in the nude. She appeared to lack control over her emotions and she became more apathetic and less talkative. Additionally, her motivation diminished until she would only eat and bathe herself.
Four years prior to the onset of her symptoms, she underwent lumbar spine surgery. There was no family history of neurological and psychiatric illness. She had six years of education and no history of alcohol or substance abuse.
Upon admittance, her general physical examination was unremarkable. The cranial nerve examination was normal. Her muscle tone was slightly increased bilaterally in the upper extremities. Bradykinesia and clumsiness in upper limbs were noted. She had mild dysmetria with finger-to-nose test bilaterally. Her gait was slow but nearly normal based, with symmetrical arm swing. Knee jerks were present but diminished and she had a right extensor plantar response.
Laboratory studies including CBC, electrolytes, chemistry, lipid profiles, liver function, thyroid function, tumor markers, autoimmune laboratories and viral antibodies were within normal limits. Electrocardiography and chest radiography were also normal.
On neuropsychological testing, her Korean Mini-Mental State Examination (K-MMSE) score was 14/30. Overall, she showed severely impaired attention, language related functions (comprehension, naming, repetition, praxis, calculation), verbal and visual memory, visuospatial and frontal executive functions ().
Results of neuropsychological test
Diffusion weighted and FLAIR axial brain MRIs demonstrated high signal intensities involving bilateral frontal, parietal, temporal and occipital cortices, especially on the right hemisphere. High signal intensities were also seen in the right caudate nucleus and the putamen, but both cerebellum and medial regions posterior to parieto-occipital sulcus were spared ().
Fig. 1 Diffusion weighted (upper row) and FLAIR (lower row) axial brain MRIs show high signal intensity in diffuse cerebral cortex with dominant involvement of right hemisphere. Cerebellum and medial occipital lobes posterior to the parieto-occipital sulcus (more ...)
Cerebrospinal fluid (CSF) examination showed no white blood cells, normal glucose and mildly elevated protein (74.2 mg/dL). An electroencephalography (EEG) on the fifth day of admission revealed intermittent 6-8 Hz of slow wave on right hemisphere. Her second EEG, taken on the eleventh admission date, showed 1-2 Hz of continuous slow waves predominantly on bilateral frontal area. During admission, she had several obsessive-compulsive behaviors such as washing her hands every 30 min and cleaning her genital area repeatedly. She wandered around the ward, however her cognitive and behavioral abnormalities did not change significantly throughout her admission. There were no significant differences on a follow-up brain MRI, conducted 19 days after admission. On the twenty-second day, a third EEG showed 3-5 Hz of continuous slow waves predominantly in the right hemisphere. Thirty-seven days after admission, she was discharged with no apparent clinical degeneration or improvement. After discharge, it was confirmed that the 14-3-3 protein in CSF was positive and sequencing of PRNP revealed a V180I mutation with methionin homozygosity at codon 129 and glutamate homozygosity at codon 219 (). Her family did not want a follow-up examination. At last contact with the family, she was still alive 18 months after onset.
Fig. 2 (A) DNA sequence at codon 180 of PRNP gene from the patient (left) and a control (right). The Letter "N" indicates a point mutation causing a substitution of GTC (Val) by ATC (Ile) at codon 180. Sequence in a control is homozygous for GTC (Val) at codon (more ...)