Intestinal pseudo-obstruction in Creutzfeldt-Jakob disease

Abstract

Creutzfeldt-Jakob disease (CJD) is a rare prion degenerative disease of the nervous system and it may be sporadic (sCJD), acquired [including variant, (vCJD)] or genetic (gCJD) [1]. CJD is characterized by rapid neuropsychiatric deterioration, but it can have a wide range of signs and symptoms [2]. Peripheral nervous system involvement is not common, and autonomic nervous system (ANS) impairment is not frequently described. Herein, we report three patients with sCJD who had intestinal pseudo-obstruction. None of them had previous history of gastrointestinal disease nor were taking any constipationinducing drugs [3]. Patient 1 was a 65-year-old healthy woman who presented with a progressive 6 month history of dementia involving short-term memory impairment, positive visual phenomena, obstipation and urinary incontinence. On neurological evaluation, she had ideomotor apraxia and dysfunction of short-term memory and visuospatial tasks. Additionally, she had a brisk pyramidal syndrome and generalized myoclonus. Brain magnetic resonance imaging (MRI) revealed cortical anterior frontal and posterior parietal restricted diffusion. Electroencephalogram showed diffuse slowing, with no periodic sharp waves. Paraneoplastic antibodies including anti-DPPX and anti-glycine receptor antibodies were negative. Whole-body fluorodeoxyglucose positron emission tomography (FDG-PET) scan did not reveal areas of hypermetabolism. Cerebral spinal fluid (CSF) analysis was unrevealing; however, CSF 14-3-3 was mildly elevated, and real-time quaking-induced conversion (RT-QuIC) was positive, indicating a probable sCJD. Obstipation and painless abdominal distention were evident since presentation. Abdominal computed tomography (CT) was remarkable for small and large bowel dilation without any obstruction point, compatible with an intestinal pseudo-obstruction (Fig. 1). She was started on prokinetic agents, with temporary symptomatic benefit, but her neurological condition inexorably worsened and death ensued in 11 months. The family refused an autopsy. Patient 2 was a 72-year-old woman who presented with a 1 month history of apathy, aphasia, memory complaints, urinary incontinence and visual hallucinations. Neurological examination revealed akinetic mutism, excessive startle to auditory stimuli, myoclonus and dysesthesia in the lower limbs. Brain MRI revealed bilateral hyperintensities on diffusion-weighted imaging (DWI) in the caudate nuclei and generalized cortico-subcortical atrophy. The patient developed severe hypotension that culminated in acute renal failure and cardiovascular instability. A few days later she developed subacute colonic pseudo-obstruction (Fig. 1). She was started on intravenous administration of high-dose methylprednisolone for 5 days, without improvement. Serum electrolytes, liver, thyroid, cortisol and neoplastic markers were all within normal values. CSF analysis revealed 0 cells/μL and normal glucose and protein concentrations. Polymerase chain reaction (PCR) tests for herpes simplex virus 1 and 2, varicella-zoster and Tropheryma whipplei were negative. CT of the thorax, abdomen and pelvis did not reveal any underlying tumour. Electroencephalography (EEG) showed triphasic periodic complexes, and 14-3-3 protein was subsequently positive in CSF. She developed atrial fibrillation with rapid ventricular response and died 19 days after admission. Necropsy confirmed the diagnosis of sCJD disease, as spongiform * Gonçalo Videira [email protected]