A 70 year‐old woman presented with progressive weakness over 3‐4 months. Initially, she noticed problems with balance, followed by tremors, forgetfulness and dysphagia. Her husband said recently she became bed bound, difficult to arouse and non‐verbal. She had previously been treated with IVIG and carbidopa/levodopa with no improvement. Her medical history included hypothyroidism and cutaneous scleroderma without systemic manifestations. Her grandfather had Parkinson’s disease. Physical exam was notable for 3/5 strength in all extremities, decreased deep tendon reflexes, sustained ankle clonus bilaterally, intention tremor, cogwheel rigidity, positive upward gaze palsy and positive dysmetria on finger‐to‐nose and heel‐to‐shin. Plantar response was equivocal bilaterally. Significant laboratory findings includes normal B12 and TSH. RPR is non‐reactive. Extensive autoimmune and vasculitis work‐up was negative.
MRI of the Brain revealed restriction on diffusion weighted imaging involving the bilateral caudate nuclei, putamen and pulvinar. EEG showed mild‐to‐moderate slowing indicative of mild‐to‐moderate diffuse cerebral dysfunction. On CSF studies, MS Panel (IgG oligoclonal band and IgG index) and Anti‐Yo/Anti‐Hu antibodies were negative; proteins tau and 14‐3‐3 were positive. With the CSF studies, MRI findings and clinical picture, she was diagnosed with Creutzfeldt‐Jakob Disease. She was discharged to a skilled nursing facility under hospice care and died one month later.
Prion diseases are neurodegenerative disorders associated with long incubation periods and rapid progression once symptoms occur. There are five types of prion diseases: Kuru, classic Creutzfeldt‐Jakob Disease (CJD), variant CJD, Gerstman‐Straussler‐Scheinker Syndrome and Fatal Familial Insomnia. Variant CJD is a separate entity from the classic forms of CJD (sporadic, familial and iatrogenic) and is represented by an earlier onset and less rapid progression.
Of the three classic forms of CJD, sporadic CJD (sCJD) constitutes 85‐95%. There are six subtypes of sCJD which are largely based on two types of abnormal prion proteins; PrPSc and the methionine/valine polymorphic codon 129. There are approximately one in one million cases of CJD a year and the average age is 57 to 62 years old with no gender or race preference.
Amongst the various forms of CJD, the two cardinal features are rapidly progressive mental deterioration and myoclonus. Corticospinal tract and extrapyramidal symptoms are found in the majority of patients. Generally, cranial nerve and sensory abnormalities are spared. The following are Centers for Disease Control criteria for CJD diagnosis: progressive dementia with a combination of myoclonus, visual or cerebellar abnormalities, pyramidal/extrapyramidal dysfunction and akinetic mutism. Diagnosis is made in conjunction with an abnormal EEG and/or positive CSF protein 14‐3‐3 and/or MRI abnormalities in the caudate and putamen. The gold standard is brain biopsy, which demonstrates spongiform changes, loss of neurons without inflammation and accumulation of prion proteins.
There is no treatment. Death uniformly occurs, normally within one year of onset of symptoms.
Hospitalists must be cognizant of the rare diseases, especially neurodegenerative diseases. These diseases are often significantly debilitating to the patient. Early recognition of these diseases provides time for adequate patient and family counseling.
To cite this abstract:Abrams‐Downey A, Brown R, Bhatnagar D. A Rare Diagnosis — It Actually Can Be That. Abstract published at Hospital Medicine 2014, March 24-27, Las Vegas, Nev. Abstract 297. Journal of Hospital Medicine. 2014; 9 (suppl 2). https://www.shmabstracts.com/abstract/a-rare-diagnosis-it-actually-can-be-that/. Accessed July 23, 2019.